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clinicalnlplab
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MS2_test

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MS212000	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Previous studies have shown that opiates increase the maximal external work performed at exhaustion in patients with chronic obstructive pulmonary disease ( COPD ) . The mechanism responsible for this improvement in exercise tolerance is unknown . The purpose of this study was to determine the effects of an oral morphine solution ( 0.8 mg/kg ) on the exercise tolerance , perception of dyspnea , and arterial blood gases of patients with COPD . Thirteen eucapnic patients with stable COPD ( FEV1 = 0.99 + /- 0.48 ) underwent duplicate incremental cycle ergometer tests to exhaustion ( Emax ) after the ingestion of placebo and after the ingestion of morphine . After the ingestion of morphine , the maximal workload increased by 18 % ( p less than 0.001 ) and the VO2 increased by 19.3 % ( p less than 0.001 ) . Ten of the 13 patients had a higher ventilation at Emax after morphine ingestion . Despite the higher ventilation at Emax after morphine , the mean Borg score was not significantly higher . At Emax after morphine ingestion , the PaO2 ( 65.8 + /- 11.6 mm Hg ) was significantly lower and the PaCO2 ( 43.5 + /- 8.3 mm Hg ) was significantly higher than at Emax after placebo ( 71.9 + /- 15.5 and 38.3 + /- 8.5 , respectively ) . When data at the highest equivalent workload were analyzed , the ventilation and the Borg scores were significantly lower , whereas the VO2 and VCO2 were comparable . From this study , we conclude that the administration of opiates can substantially increase the exercise capacity of patients with COPD . The improved exercise tolerance appears to be related to both a higher PaCO2 result ing in lowered ventilation requirements for a given workload and also to a reduced perception of breathlessness for a given level of ventilation In six healthy subjects , respiration and the sensation of breathlessness were assessed during submaximal exercise and the subsequent recovery . The overall responses were expressed by the relationship of breathlessness to minute volume . Because of the high subjective component in the assessment s , validation of the method in these particular subjects was an integral part of the study . The relationship of breathlessness to ventilation during identical periods of exercise was highly reproducible and sensitivity was demonstrated by an alteration in this relationship in the presence of an inspiratory resistance . Codeine at a dose of 60 mg by mouth was compared with placebo , each treatment being given on two occasions . The study was conducted in a double-blind fashion with r and omization of the order of treatments . Codeine at this dose allowed higher levels of carbon dioxide to be tolerated during breath-holding ; oxygen uptakes at rest and during exercise were unaffected . Ventilation and breathlessness at the end of exercise were each slightly but significantly reduced by codeine but the relationship between breathlessness and ventilation was not changed . Codeine did not prevent detection of an inspiratory resistance We have shown previously that the administration of morphine ( 0.8 mg/kg ) to patients with COPD increases the VO2max by 19.3 percent . A recent study demonstrated that the administration of low-dose nebulized morphine ( approximately 2 mg ) increased the endurance time of patients with severe lung disease by 1 min ( 35 percent ) with few systemic side effects . This double-blind crossover study evaluated the effects of various doses of nebulized morphine ( 0 , 1 , 4 , and 10 mg ) on the exercise tolerance and the psychologic status of COPD patients . In the present study , eight COPD patients ( FEV1 = 0.90 + /- 0.26 L , workload max = 76 + /- 29 W , VO2max = 950 + /- 264 ml , VEmax = 34 + /- 7 L ) , who were ventilatory limited were tested on four separate days . On each testing day , the patients underwent incremental exercise testing and psychologic testing before and 45 min after receiving the nebulized solution . The mean changes ( + /- SD ) in the exercise test results after each of the four different regimens were as follows : [ table : see text ] Although there tended to be larger increases in the workload , VO2max , and VEmax after the largest dose of morphine , none of the changes was statistically significant . Likewise , there were no significant differences in spirometry , resting metabolic measurements , or psychologic test scores after the four different regimens . We conclude that aerosolized morphine in the doses used in this study has no significant beneficial effect on the exercise tolerance of patients with COPD OBJECTIVES We sought to test the hypothesis that suppression of chemosensitivity ( respiratory response to arterial blood gases ) with dihydrocodeine may improve dyspnea and exercise tolerance in patients with chronic heart failure . BACKGROUND Exertional dyspnea is a common limiting symptom in patients with chronic heart failure . The mechanisms underlying this symptom are not fully understood but may be related to increased ventilation caused , in part , by the augmentation of chemosensitivity . Suppression of chemosensitivity with mild opiates may thus improve this symptom as well as exercise tolerance . METHODS Twelve men with chronic heart failure ( mean [ + /-SE ] age 65.5 + /- 1.5 years , range 58 to 75 ; left ventricular ejection fraction 21.3 + /- 3.0 % , range 8 to 39 ) received placebo or dihydrocodeine ( 1 mg/kg body weight ) on two separate days in a r and omized , double-blind design . One hour later , hypoxic and hypercapnic chemosensitivities were assessed using the transient inhalations of pure nitrogen and the rebreathing of 7 % carbon dioxide in 93 % oxygen , followed by treadmill cardiopulmonary exercise testing . The symptoms of dyspnea and fatigue during the exercise test were assessed using a modified Borg scale from 0 to 10 . RESULTS There was a significant fall in hypoxic and hypercapnic chemosensitivities with dihydrocodeine administration compared with placebo ( 0.447 + /- 0.096 vs. 0.746 + /- 0.104 liter/min per percent arterial oxygen saturation , p = 0.005 ; 2,480 + /- 0.234 vs. 2.966 + /- 0.283 liter/min per mm Hg , p = 0.01 , respectively ) . Exercise duration was prolonged from 455 + /- 27 s on placebo to 512 + /- 27 s ( p = 0.001 ) with dihydrocodeine , and peak oxygen consumption increased from 18.0 + /- 0.6 to 19.7 + /- 0.6 ml/kg per min ( p = 0.002 ) . The ventilatory response to exercise , characterized by the regression slope relating minute ventilation to carbon dioxide output , decreased from 34.19 + /- 2.35 to 30.85 + /- 1.91 ( p = 0.01 ) . With dihydrocodeine administration , the change in the modified Borg score for dyspnea was -0.80 ( p = 0.003 ) at 6 min and -0.33 ( p = 0.52 ) at peak exercise , whereas that for fatigue did not change significantly . Arterial oxygen saturation was maintained during exercise despite dihydrocodeine administration ( 99.3 % at rest vs. 98.9 % at peak exercise , p = 0.21 ) . CONCLUSIONS Augmented chemosensitivity is important in the pathophysiology of chronic heart failure . Its suppression with dihydrocodeine was associated with a reduction of exercise ventilation , an improvement in exercise tolerance and a decrease in breathlessness . Pharmacologic modulation of chemosensitivity may benefit patients with chronic heart failure and merits further investigation OBJECTIVE We have shown that the administration of 0.8 mg/kg of morphine ( M ) to patients with COPD result ed in a 20 % increase in the maximum oxygen consumption ( Vo2max ) , but was associated with significant drowsiness and euphoria . The objective of the present study was to ascertain whether lower doses of M alone or in combination with prochlorperazine ( PC ) or promethazine ( P ) could elicit significant increases in exercise tolerance . DESIGN The exercise capacity , psychological status , and reaction times were assessed before and 60 min after the patients received placebo ( PLAC ) , 30 mg M orally , 30 mg M plus 10 mg PC ( M-PC ) , or 30 mg M plus 25 mg P ( M-P ) in a r and omized double-blind crossover study . In a secondary study , nine patients were tested on three separate days before and after receiving PLAC , 25 mg P , or 30 mg M plus 25 mg P. PATIENTS Seven COPD patients ( FEV1=0.99 + /- 0.30 L , Vo2max=990 + /- 315 mL/min ) who were ventilatory-limited . SETTING Veterans Affairs medical center . RESULTS After the patients ingested M-P , the increase in the Vo2max ( 129.0 + /- 104 mL/min ) , the workload ( 10.0 + /- 6.5 W ) and the maximum minute ventilation ( 4.0 + /- 3.9 L/min ) were significantly greater ( p<0.05 ) than after PLAC ingestion ( -4.8 + /- 79 mL/min , 1.4 + /- 6.9 W , and -1.6 + /- 2.4 L/min , respectively ) . Changes after the ingestion of M , P , o r M-PC were intermediate . The M-PC combination adversely affected the patient 's reported mental status ( Bond visual analog scale ) more than the M-P or M regimens . No regimen significantly affected the reaction time . CONCLUSIONS We conclude that the administration of 30 mg of M plus 25 mg of P significantly improves the exercise tolerance of patients with COPD , without significantly impairing the mental capabilities of the subjects . The utility of this regimen over longer time periods needs to be evaluated Systemic opiates may relieve dyspnoea and improve exercise tolerance in patients with chronic obstructive pulmonary disease ( COPD ) . Small doses of inhaled opiates may have similar effects ; however , recent studies have shown no benefit . We studied higher doses of inhaled morphine and measured systemic absorption to determine whether any beneficial actions are local or systemic . Twenty and 40 mg doses and 0.9 % saline were nebulized in a r and omized , double-blind study of 16 patients with stable COPD . Patients performed 6 min walk tests immediately after the nebulized test solution ( Walk 1 ) and again 60 min later ( Walk 2 ) . Arterial oxygen saturation ( Sa , O2 ) , modified Borg dyspnoea score and cardiac frequency were recorded during each walk . There was no difference between placebo and either dose of nebulized morphine on these measurements . The higher dose of nebulized morphine achieved a higher plasma concentration . The highest plasma concentration was measured immediately after nebulization , and this decreased steadily in the hour thereafter ( p<0.002 ) . There was no correlation between the change in walk distance and the change in plasma morphine concentration after either dose of nebulized morphine . We conclude that higher doses of nebulized morphine do not improve exercise endurance or relieve dyspnoea in patients with chronic obstructive pulmonary disease , and that morphine is rapidly absorbed systemically after inhalation BACKGROUND : Inhaled morphine has previously been shown to increase exercise endurance in patients with chronic lung disease . A similar study was performed to determine whether inhaled morphine reduces the sensation of breathlessness in this group of patients . METHODS : A r and omised double blind study on the effect of nebulised morphine on both exercise induced breathlessness and maximum achievable power output using isotonic saline as a control was performed in 10 patients with stable chronic lung disease . Each subject performed a progressive exercise test ( Jones ' stage I ) on an electrically braked cycle ergometer . The work load was increased by 10 watts per minute and subjects exercised to exhaustion . At the end of each minute of exercise patients were asked to rate their degree of breathlessness according to a modified Borg scale . All subjects were r and omised to receive either inhaled morphine sulphate 1 mg/ml ( 5 ml ) or isotonic saline ( 5 ml ) by wet nebulisation . The effect of morphine and saline on the achieved exercise capacity and the development of breathlessness during exercise was tested on separate days . RESULTS : The mean dose of morphine inhaled was 1.24 mg . There was no difference in maximum power output achieved , minute ventilation at maximum power output , nor the degree of breathlessness at maximum power output between the groups treated with morphine and placebo . The degree of breathlessness was related to the power output achieved during exercise by a power function relationship ( mean r : morphine = 0.86 , saline = 0.87 ) . However , there was a wide variation in the sensation for any given power output in both groups . There was no difference in the group mean slopes ( morphine = 1.15 , saline = 1.00 ) or intercepts ( morphine = 0.07 , saline = 0.15 ) in this relationship between the morphine and saline treatment groups . CONCLUSIONS : In patients with severe chronic lung disease inhaled morphine in the doses used in this study does not relieve exercise induced breathlessness nor does it increase maximum power output achieved during progressive exercise The purpose of this placebo-controlled , double-blind , r and omized study was to assess the effect of nebulized morphine on dyspnoea perceived at rest by patients with advanced disease . Seventeen hospital in- patients with disabling d Output:	A small but statistically significant positive effect of opioids was seen on breathlessness in the analysis of studies using non-nebulised opioids . No evidence was found to support the use of nebulised opioids .
MS212001	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Aims Mineralocorticoid receptor antagonists ( MRAs ) improve outcomes in patients with heart failure and reduced left ventricular ejection fraction ( HFrEF ) , but their use is limited by hyperkalaemia and /or worsening renal function ( WRF ) . BAY 94 - 8862 is a highly selective and strongly potent non-steroidal MRA . We investigated its safety and tolerability in patients with HFrEF associated with mild or moderate chronic kidney disease ( CKD ) . Methods and results This r and omized , controlled , phase II trial consisted of two parts . In part A , the safety and tolerability of oral BAY 94 - 8862 [ 2.5 , 5 , or 10 mg once daily ( q.d . ) ] was assessed in 65 patients with HFrEF and mild CKD . In part B , BAY 94 - 8862 ( 2.5 , 5 , or 10 mg q.d . , or 5 mg twice daily ) was compared with placebo and open-label spironolactone ( 25 or 50 mg/day ) in 392 patients with HFrEF and moderate CKD . BAY 94 - 8862 was associated with significantly smaller mean increases in serum potassium concentration than spironolactone ( 0.04–0.30 and 0.45 mmol/L , respectively , P < 0.0001–0.0107 ) and lower incidences of hyperkalaemia ( 5.3 and 12.7 % , respectively , P = 0.048 ) and WRF . BAY 94 - 8862 decreased the levels of B-type natriuretic peptide ( BNP ) , amino-terminal proBNP , and albuminuria at least as much as spironolactone . Adverse events related to BAY 94 - 8862 were infrequent and mostly mild . Conclusion In patients with HFrEF and moderate CKD , BAY 94 - 8862 5–10 mg/day was at least as effective as spironolactone 25 or 50 mg/day in decreasing biomarkers of haemodynamic stress , but it was associated with lower incidences of hyperkalaemia and WRF BACKGROUND We evaluated the role of aldosterone as a mediator of renal inflammation and fibrosis in a rat model of aldosterone/salt hypertension using the selective aldosterone blocker , eplerenone . METHODS Unnephrectomized , Sprague-Dawley rats were given 1 % NaCl ( salt ) to drink and r and omized to receive treatment for 28 days : vehicle infusion ( control ) ; 0.75 microg/hour aldosterone subcutaneous infusion ; or aldosterone infusion + 100 mg/kg/day oral dose of eplerenone . Blood pressure and urinary albumin were measured and kidneys were evaluated histologically . Renal injury , inflammation , and fibrosis were assessed by immunohistochemistry , in situ hybridization , and reverse transcription-polymerase chain reaction ( RT-PCR ) . RESULTS Aldosterone/salt induced severe hypertension compared to controls ( 220 + /- 4 mm Hg vs. 131 + /- 4 mm Hg , P < 0.05 ) , which was partially attenuated by eplerenone ( 179 + /- 4 mm Hg , P < 0.05 ) . In aldosterone/salt treated rats , renal histopathologic evaluation revealed severe vascular and glomerular sclerosis , fibrinoid necrosis and thrombosis , interstitial leukocyte infiltration , and tubular damage and regeneration . Aldosterone/salt increased circulating osteopontin ( 925.0 + /- 80.2 ng/mL vs. 53.6 + /- 6.3 ng/mL ) and albuminuria ( 75.8 + /- 10.9 mg/24 hours vs. 13.2 + /- 3.0 mg/24 hours ) compared to controls and increased expression of proinflammatory molecules . Treatment with eplerenone reduced systemic osteopontin ( 58.3 + /- 4.2 ng/mL ) , albuminuria ( 41.5 + /- 7.2 mg/24 hours ) , and proinflammatory gene expression : osteopontin ( OPN ) , monocyte chemoattractant protein-1 ( MCP-1 ) , interleukin-6 ( IL-6 ) , and interleukin-1beta ( IL-1beta ) . CONCLUSION These findings indicate that aldosterone/salt-induced renal injury and fibrosis has inflammatory components involving macrophage infiltration and cytokine up-regulation . Attenuation of renal damage and inflammation by eplerenone supports the protective effects of aldosterone blockade in hypertensive renal disease IMPORTANCE Steroidal mineralocorticoid receptor antagonists , when added to a renin-angiotensin system blocker , further reduce proteinuria in patients with chronic kidney disease but may be underused because of a high risk of adverse events . OBJECTIVE To evaluate the safety and efficacy of different oral doses of the nonsteroidal mineralocorticoid receptor antagonist finerenone , given for 90 days to patients with diabetes and high or very high albuminuria who are receiving an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled , parallel-group study conducted at 148 sites in 23 countries . Patients were recruited from June 2013 to February 2014 and the study was completed in August 2014 . Of 1501 screened patients , 823 were r and omized and 821 received study drug . INTERVENTIONS Participants were r and omly assigned to receive oral , once-daily finerenone ( 1.25 mg/d , n = 96 ; 2.5 mg/d , n = 92 ; 5 mg/d , n = 100 ; 7.5 mg/d , n = 97 ; 10 mg/d , n = 98 ; 15 mg/d , n = 125 ; and 25 mg/d , n = 119 ) or matching placebo ( n = 94 ) for 90 days . MAIN OUTCOMES AND MEASURES The primary outcome was the ratio of the urinary albumin-creatinine ratio ( UACR ) at day 90 vs at baseline . Safety end points were changes from baseline in serum potassium and estimated glomerular filtration rate . RESULTS The mean age of the participants was 64.2 years ; 78 % were male . At baseline , 36.7 % of patients treated had very high albuminuria ( UACR ≥300 mg/g ) and 40.0 % had an estimated glomerular filtration rate of 60 mL/min/1.73 m2 or lower . Finerenone demonstrated a dose-dependent reduction in UACR . The primary outcome , the placebo-corrected mean ratio of the UACR at day 90 relative to baseline , was reduced in the finerenone 7.5- , 10- , 15- , and 20-mg/d groups ( for 7.5 mg/d , 0.79 [ 90 % CI , 0.68 - 0.91 ; P = .004 ] ; for 10 mg/d , 0.76 [ 90 % CI , 0.65 - 0.88 ; P = .001 ] ; for 15 mg/d , 0.67 [ 90 % CI , 0.58 - 0.77 ; P<.001 ] ; for 20 mg/d , 0.62 [ 90 % CI , 0.54 - 0.72 ; P < .001 ] ) . The prespecified secondary outcome of hyperkalemia leading to discontinuation was not observed in the placebo and finerenone 10-mg/d groups ; incidences in the finerenone 7.5- , 15- , and 20-mg/d groups were 2.1 % , 3.2 % , and 1.7 % , respectively . There were no differences in the incidence of the prespecified secondary outcome of an estimated glomerular filtration rate decrease of 30 % or more or in incidences of adverse events and serious adverse events between the placebo and finerenone groups . CONCLUSIONS AND RELEVANCE Among patients with diabetic nephropathy , most receiving an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker , the addition of finerenone compared with placebo result ed in improvement in the urinary albumin-creatinine ratio . Further trials are needed to compare finerenone with other active medications . TRIAL REGISTRATION clinical trials.gov Identifier : NCT1874431 Output:	Interestingly , recent evidence suggests that MR signaling is increased by Rac1 activation , independent of lig and binding to MR , and that Rac1 was shown to be activated by angiotensin II and diabetic conditions [ 5 ] . There are many convincing data suggesting that MRAs may provide additional reno-protective effects in patients experiencing the aldosterone escape phenomenon during RAS blockade treatment [ 6 ] .
MS212002	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Impaired motor development can significantly affect a child 's life and may result in an increased risk of a range of physical and psychological disorders . Active video game ( AVG ) interventions have been demonstrated to enhance motor skills in children with Developmental Coordination Disorder ( DCD ) ; however a home-based intervention has not been assessed . OBJECTIVES The primary aim of this study was to compare the changes in motor coordination between a 16 week period of AVG use , with 16 weeks of normal activities ( NAG ) . The secondary aim was to compare the child and parent perceptions of their physical performance between the AVG and NAG conditions . METHODS Twenty-one 9 - 12 year olds ( 10 males ) were confirmed to be at risk of DCD ( ⩽ 16th percentile Movement Assessment Battery for Children-2nd edition ( MABC-2 ) and ⩽ 15th percentile Developmental Coordination Disorder Question naire ( DCDQ ) ) and participated in this crossover r and omised and controlled trial . Data was collected at study entry , after the first 16 week condition and following the final 16 week condition , including ; ( 1 ) the MABC-2 , ( 2 ) three-dimensional motion analysis of single leg balance and finger-nose tasks , and ( 3 ) parent perception of physical skills . Participant perception of physical skills was collected only after the first and second conditions . RESULTS There was no significant difference between AVG and NAG for any of the primary variables including the MABC-2 , balance centre-of-mass path distance and finger-nose path distance . There was no significant intervention effect for secondary measures of motor coordination ; however the children perceived their motor skills to be significantly enhanced as a result of the AVG intervention in comparison to the period of no intervention . CONCLUSION A 16 week home based AVG intervention did not enhance motor skills in children with DCD , although they perceived their physical skills to be significantly improved . TRIAL REGISTRATION Australia and New Zeal and Clinical trials Registry ( ACTRN 12611000400965 ) BACKGROUND Little is known about the influence of practice schedules on motor learning and skills transfer in children with and without developmental coordination disorder ( DCD ) . Underst and ing how practice schedules affect motor learning is necessary for motor skills development and rehabilitation . AIMS The study investigated whether active video games ( exergames ) training delivered under variable practice led to better learning and transfer than repetitive practice . METHODS AND PROCEDURES 111 children aged 6 - 10 years ( M=8.0 , SD=1.0 ) with no active exergaming experience were r and omized to receive exergames training delivered under variable ( Variable Game Group ( VGG ) , n=56 ) or repetitive practice schedule ( Repetitive Game Group ( RGG ) , n=55 ) . Half the participants were identified as DCD using the DSM-5 criteria , while the rest were typically developing ( TD ) , age-matched children . Both groups participated in two 20min sessions per week for 5 weeks . OUTCOMES AND RESULTS Both participant groups ( TD and DCD ) improved equally well on game performance . There was no significant difference in positive transfer to balance tasks between practice schedules ( Repetitive and Variable ) and participant groups ( TD and DCD ) . CONCLUSIONS AND IMPLICATION S Children with and without DCD learn balance skills quite well when exposed to exergames . Gains in learning and transfer are similar regardless of the form of practice schedule employed . WHAT THIS PAPER ADDS This is the first paper to compare the effect of practice schedules on learning in children with DCD and those with typical development . No differences in motor learning were found between repetitive and variable practice schedules . When children with and without DCD spend the same amount of time on exergames , they do not show any differences in acquisition of motor skills . Transfer of motor skills is similar in children with and without DCD regardless of differences in practice schedules Background Adolescents with low motor competence participate less in physical activity and tend to exhibit decreased physical fitness compared to their peers with high motor competence . It is therefore essential to identify new methods of enhancing physical fitness in this population . Active video games ( AVG ) have been shown to improve motor performance , yet investigations of its impact on physical fitness are limited . The objective of this study was to examine the impact of the grade d Wii protocol in adolescent girls with probable Developmental Coordination Disorder ( p-DCD ) . Methods A single-group pre-post design was conducted to assess the impact of a newly developed Wii protocol in adolescent girls attending school in a low income community of Cape Town , South Africa . Sixteen participants ( aged 13 - 16 years ) with p-DCD ( ≤16th percentile on the MABC-2 test ) were recruited . Participants received 45 min Wii training for 14 weeks . Outcome measures included the six-minute walk distance and repeated sprint ability . Information on heart rate , enjoyment and perceived exertion ratings were also collected . Results Significant improvements in aerobic and anaerobic fitness were observed . The participants reported high enjoyment scores and low perceived exertion ratings . The grade d Wii protocol was easily adaptable and required little re sources ( space , equipment and expertise ) to administer . Conclusions The findings provide preliminary evidence to support the use of the grade d Wii protocol for promoting physical fitness in adolescent girls with p-DCD . Further studies are needed to confirm these results and to vali date the clinical efficacy of the protocol in a larger sample with a more robust design The purpose of this study was to investigate the effects of training with the Wii-balance board on balance and balance-related skills of children with poor motor performance . Twenty-nine children ( 23 boys , 6 girls ; aged 7 - 12 years ) participated in this study and were r and omly assigned to an experimental and control group . All children scored below the 16th percentile on a st and ardized test of motor ability and balance skills ( Movement Assessment Battery for children ( M-ABC-2 ) ) . Before and after a six-week Wii-intervention ( M=8h , 22 min , SD=53 min ) , the balance skills of the experimental group and control group were measured with the M-ABC-2 and the Bruininks-Oseretsky test of motor proficiency ( BOT-2 ) . Both groups improved on all tests . The M-ABC-2 and the BOT-2 total balance-scores of the experimental group improved significantly from pre to post intervention , whereas those of the control group showed no significant progress . This result ed in significant interaction-effects , favoring the experimental children . No transfer-effects of the intervention on balance-related skills were demonstrated . Our findings showed that the Wii-balance board is an effective intervention for children with poor balance control . Further development and investigation of the intervention could be directed toward the implementation of the newly acquired balance-skills in daily life Objective Transfer of motor skills is the ultimate goal of motor training in rehabilitation practice . In children with Developmental Coordination Disorder ( DCD ) , very little is known about how skills are transferred from training situations to real life context s. In this study we examined the influence of two types of practice on transfer of motor skills acquired in a virtual reality ( VR ) environment . Method One hundred and eleven children with DCD and their typically developing ( TD ) peers , aged 6–10 years ( M = 8.0 SD = 1.0 ) were r and omly assigned to either variable ( n = 56 ) or repetitive practice ( n = 55 ) . Participants in the repetitive practice played the same exergame ( ski slalom ) twice weekly for 20 minutes , over a period of 5 weeks , while those in the variable group played 10 different games . Motor skills such as balance tasks ( hopping ) , running and agility tasks , ball skills and functional activities were evaluated before and after 5 weeks of training . Results ANOVA repeated measures indicated that both DCD and TD children demonstrated transfer effects to real life skills with identical and non-identical elements at exactly the same rate , irrespective of the type of practice they were assigned to . Conclusion Based on these findings , we conclude that motor skills acquired in the VR environment , transfers to real world context s in similar proportions for both TD and DCD children . The type of practice adopted does not seem to influence children ’s ability to transfer skills acquired in an exergame to life situations but the number of identical elements does Neuromotor Task Training ( NTT ) and Nintendo Wii Fit Training ( Wii training ) are both task-based interventions used to improve performance in children with motor coordination problems . The aim of this study was to compare the efficacy of these two interventions on the motor performance , isometric strength and cardiorespiratory fitness ( aerobic and anaerobic capacity ) of children with Developmental Coordination Disorder ( DCD ) attending mainstream schools in a low-income setting . A pragmatic , quasi-experimental study design was utilized . Children between the ages of 6 - 10 years , who scored at or below the 16th percentile on the Movement Assessment Battery for Children-2 ( MABC-2 ) and whose teacher reported a functional motor problem , were allocated to either NTT ( n=37 ) or Wii training ( n=19 ) groups depending on school of attendance . The MABC-2 , a h and -held dynamometer , the Functional Strength Measure , the Muscle Power Sprint Test and the 20 m Shuttle Run Test were used to assess performance at baseline and after the intervention . The main findings show that the mean motor performance scores of both groups improved over the study period . However , significant differences in improvement were detected between groups , with the NTT group showing greater improvement in motor performance , functional strength and cardiorespiratory fitness . No improvements in isometric strength were seen in either group . The Wii training group showed significant improvement in anaerobic performance . This study provides evidence to support the use of both the Wii Training and NTT for children with DCD . However , in comparison to Wii training , the NTT approach yields superior results across measures of motor proficiency , cardiorespiratory fitness and functional strength . The decision to use either approach may be influenced by re sources and time constraints OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity OBJECTIVES Physical and occupational therapists have started to use the Nintendo Wii ™ gaming system with adults and children as part of their regular treatment . Despite the growing use of the Wii and trend towards evidence -based practice , limited evidence is available on the effectiveness of virtual reality using the Wii for children with developmental delay . The purpose of this study was to determine the feasibility and preliminary effectiveness of a low-cost gaming system for young children with developmental delay . STUDY DESIGN Single-blind , r and omised controlled trial . PARTICIPANTS AND SETTING Forty children with developmental delay ( age 39 to 58 months ) who attended a segregated or integrated preschool participated in this study . All children 's parents read and signed an informed consent form approved by the institutional review board . Children were assigned at r and om to an experimental ( Wii ) group ( n=20 ) or a control group ( n=20 ) . INTERVENTION Two weekly sessions for 10 weeks using Nintendo Wii Sports ™ and Nintendo Wii Fit ™ , including balance , strength training and aerobics games . MAIN OUTCOME MEASURES Participants were evaluated 1 week before and 1 week after the programme by a blinded investigator . Primary outcomes were gait speed , timed up and go test , single leg stance test , five-times-sit-to-st and test , timed up and down stairs test , 2-minute walk test and grip strength . The Gross Motor Function Measure ( GMFM ) was used to assess gross motor skills . RESULTS The two groups were homogenous regarding all parameters at baseline . The Wii training was feasible and enjoyable for those in the experimental group . There were no adverse effects or injuries reported over 267 training sessions . Comparison of groups following the intervention indicated that the experimental group showed significant improvements compared with the control group in single leg stance test { mean difference 1.03 [ st and ard deviation ( SD ) 1.7 ] , 95 % confidence interval ( CI ) 0.2 to 1.9 ; P= Output:	Mixed effects of video game intervention on outcome were found , with conflicting evidence across studies . Studies that reported on feasibility found most children enjoyed and adhered to the video game interventions .
MS212003	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The objective of this study is to compare the efficacy and safety of diode laser enucleation of the prostate ( DiLEP ) with plasmakinetic enucleation of the prostate ( PKEP ) for symptomatic benign prostatic hyperplasia ( BPH ) patients with large prostate ( volume > 80 ml ) . From January 2013 to June 2014 , 80 consecutive patients were r and omized treated with DiLEP ( n = 40 ) or PKEP ( n = 40 ) . Perioperative and postoperative outcome data were assessed during a 1-year follow-up . There were no significant preoperative differences between the two surgical groups . The mean prostate volumes in the DiLEP and PKEP groups were 98.6 and 93.3 ml , respectively . DiLEP was equivalent to PKEP in improvement in International Prostate Symptom Score ( IPSS ) , quality of life scores , and maximum flow rate . Compared with PKEP , patients treated with DiLEP showed a lower risk of blood loss ( P < 0.01 ) , shorter bladder irrigation and catheterization times ( P < 0.01 ) , as well as shorter hospital stays ( P < 0.01 ) . Moreover , the DiLEP group was significantly superior to bipolar plasmakinetic group in the irritative symptoms . However , the operation time of the DiLEP group was longer than that of PKEP group ( P = 0.02 ) . Both DiLEP and PKEP are safe and effective methods for the treatment of BPH in large prostates ( volume > 80 ml ) . Compared with PKEP , DiLEP provides a decreased risk of hemorrhage , reduced bladder irrigation , and catheterization times , as well as shorter hospital stays Purpose Bipolar endoscopic enucleation of the prostate ( BEEP ) was recommended by the 2016 EAU guidelines as the first choice of surgical treatment in men with a substantially enlarged prostate and moderate-to-severe lower urinary tract symptoms . The main aim of this study was to compare a modified diode laser enucleation of the prostate ( DiLEP ) to BEEP . Methods A total of 114 patients with prostate ( 20–160 mL ) were r and omized 1:1 into either DiLEP or BEEP in a dual-centre , non-inferiority- design r and omized-controlled trial . The primary outcomes included Qmax and IPSS at 12 months . Non-inferiority was evaluated by comparing the two-sided 95 % CI for the mean differences of Qmax and IPSS . Secondary endpoints included other perioperative parameters , postoperative micturition variables , and complication rate . Results A total of 111 patients ( 97 % ) had completed the intent-to-treat analysis , The results showed that DiLEP was comparable to BEEP regarding Qmax ( 28.0 ± 7.0 vs. 28.1 ± 7.2 mL/s ) and IPSS ( 3.0 ± 2.2 vs. 2.9 ± 2.6 ) at 12 months , the non-inferiority was met for both Qmax and IPSS . There were also no significant difference between two groups regarding tissue removal rate ( 71.8 vs. 73.8 % ) , hemoglobin decrease ( 0.33 ± 0.66 vs. 0.36 ± 0.75 g/dL ) , sodium decrease ( 1.0 ± 2.7 vs. 0.3 ± 2.9 mmol/L ) , and Clavien III complications ( 5.3 vs. 1.8 % ) at 12 months . Conclusions This DiLEP is an anatomical endoscopic enucleation technique for the treatment of benign prostatic hyperplasia , it is non-inferior to BEEP regarding Qmax and IPSS at 12 months postoperatively PURPOSE To compare the safety and efficacy of thulium laser enucleation of the prostate ( ThuLEP ) with plasmakinetic enucleation of the prostate ( PKEP ) . METHODS A total of 127 patients with benign prostatic hyperplasia ( BPH ) were r and omized to either ThuLEP ( n = 61 ) or PKEP ( n = 66 ) . All patients were assessed preoperatively and followed up at 3 , 6 , and 12 months postoperatively . Baseline characteristics of the patients , perioperative data , postoperative outcomes , and complications were recorded . RESULTS The decrease in hemoglobin level and the catheter time were statistically significantly lower in the ThuLEP group compared with the PKEP group ( 0.80 ± 0.49 vs 0.99 ± 0.52 , p = 0.037 , and 1.85 ± 0.94 vs 2.28 ± 1.34 , p = 0.042 ) . There were no statistical differences in complications between the two groups ( p > 0.05 ) . There was a significant improvement in 3 , 6 , and 12 months ' parameters compared with preoperative values ( p < 0.001 ) . Assessment at the 12-month follow-up showed no difference in urinary parameters between the two groups . CONCLUSIONS ThuLEP and PKEP are both safe and efficient procedures for the treatment of patients with BPH . Compared with PKEP , ThuLEP provided less risk of hemorrhage and shorter catheter time , although the differences may be of little clinical relevance . Further well- design ed trials with extended follow-up and larger sample size are needed to draw final conclusions about the efficacy of the two procedures OBJECTIVE To compare the clinical outcomes between thulium laser transurethral enucleation of the prostate ( ThuLEP ) and plasmakinetic bipolar resection of the prostate ( PKRP ) for treating benign prostatic hyperplasia ( BPH ) in a prospect i ve r and omized trial with 18 months of follow-up . METHODS The study r and omized 158 consecutive patients with BPH to ThuLEP ( n = 79 ) or PKRP ( n = 79 ) . All patients were evaluated preoperatively and at 1 , 3 , 6 , 12 , and 18 months after surgery by International Prostate Symptom Score ( IPSS ) , quality of life score ( QOLS ) , maximum flow rate ( Qmax ) , and postvoid residual urine volume ( PVR ) . RESULTS The 79 patients in each study arm each showed no significant difference in preoperative parameters . Compared with PKRP , ThuLEP required a longer operation time ( 65.4 vs 47.4 minutes , P = .022 ) but result ed in less hemoglobin decrease ( 0.15 vs 0.30 g/dL , P = .045 ) . ThuLEP also needed less catheterization time ( 2.1 vs 3.5 days , P = .031 ) , irrigation volume ( 12.4 vs 27.2 L , P = .022 ) , and hospital stay ( 2.5 vs 4.6 days , P = .026 ) . During the 1 , 3 , 6 , 12 , and 18 months of follow-up , the procedures did not demonstrate a significant difference in Qmax , IPSS , PVR , and QOLS . CONCLUSION ThuLEP and PKRP both relieve lower urinary tract symptoms equally , with high efficacy and safety . ThuLEP was statistically superior to PKRP in blood loss , catheterization time , irrigation volume , and hospital stay but inferior to PKRP in operation time . However , procedures did not differ significantly in Qmax , IPSS , PVR , and QOLS through the 18 months of follow-up Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more To evaluate the safety and efficacy of plasmakinetic enucleation of the prostate ( PKEP ) for the treatment of symptomatic benign prostatic hyperplasia ( BPH ) compared with 160-W lithium triboride laser photoselective vaporization of the prostate ( PVP ) . From February 2011 to July 2012 , a prospect i ve nonr and omized study was performed . One-hundred one patients underwent PKEP , and 110 underwent PVP . No severe intraoperative complications were recorded , and none of the patients in either group required a blood transfusion . Shorter catheterization time ( 38.14 ± 23.64 h vs 72.54 ± 28.38 h , P < 0.001 ) and hospitalization ( 2.32 ± 1.25 days vs 4.07 ± 1.23 days , P < 0.001 ) were recorded in the PVP group . At 12-month postoperatively , the PKEP group had a maintained and statistically improvement in International Prostate Symptom Score ( IPSS ) ( 4.07 ± 2.07 vs 5.00 ± 2.10 ; P < 0.001 ) , quality of life ( QoL ) ( 1.08 ± 0.72 vs 1.35 ± 0.72 ; P= 0.007 ) , maximal urinary flow rate ( Qmax ) ( 24.75 ± 5.87 ml s−1 vs 22.03 ± 5.04 ml s−1 ; P < 0.001 ) , postvoid residual urine volume ( PVR ) ( 14.29 ± 6.97 ml vs 17.00 ± 6.11 ml ; P= 0.001 ) , and prostate-specific antigen ( PSA ) value ( 0.78 ± 0.57 ng ml−1 vs 1.27 ± 1.07 ng ml−1 ; P < 0.001 ) . Both PKEP and PVP relieve low urinary tract symptoms ( LUTS ) due to BPH with low complication rates . PKEP can completely remove prostatic adenoma while the total amount of tissue removed by PVP is less than that can be removed by PKEP . Based on our study of the follow-up , PKEP provides better postoperative outcomes than PVP PURPOSE Transurethral resection of the prostate has for decades been the st and ard surgical therapy for lower urinary tract symptoms secondary to benign prostatic hyperplasia , the most common benign neoplasm in men . To generate a contemporary reference for evolving medical and minimally invasive therapies we analyzed complications and immediate outcomes of transurethral prostate resection in a statewide multicenter study . MATERIAL S AND METHODS We prospect ively evaluated 10,654 patients undergoing transurethral prostate resection in the state of Bavaria , Germany from January 1 , 2002 until December 31 , 2003 . Case records containing 54 items concerning preoperative status , operation details , complications and immediate outcome , were recorded for each patient . RESULTS The mortality rate for transurethral prostate resection was 0.10 % . The cumulative short-term morbidity rate was 11.1 % . The most relevant complications were failure to void ( 5.8 % ) , surgical revision ( 5.6 % ) , significant urinary tract infection ( 3.6 % ) , bleeding requiring transfusions ( 2.9 % ) and transurethral resection syndrome ( 1.4 % ) . The resected tissue averaged 28.4 gm . Incidental carcinoma of the prostate was diagnosed by histological examination in 9.8 % of patients . Urinary peak flow rate increased significantly to 21.6 + /- 9.4 ml per second ( baseline 10.4 + /- 6.8 ml per second , 1 tail p < 0.0001 ) , while post-void residual decreased to 31.1 + /- 73.0 ml ( baseline 180.3 + /- 296.9 ml , 1-tail p < 0.0001 ) . CONCLUSIONS In a large scale evaluation comprising 44 mostly nonacademic urological departments in Bavaria , unique real-world data for transurethral prostate resection were prospect ively generated . This most contemporary information should be of use to potential patients and facilitate subsumption of emerging surgical and nonsurgical benign prostatic hyperplasia treatment options PURPOSE We compared plasmakinetic resection with holmium laser enucleation of the prostate for the treatment of benign prostatic hyperplasia by analyzing 2-year followup data from a prospect i ve r and omized clinical trial . MATERIAL S AND METHODS A total of 280 patients were r and omly treated with plasmakinetic resection or holmium laser enucleation of the prostate . Perioperative and postoperative outcome data were obtained during a 2-year followup . RESULTS No significant differences between the 2 surgical groups were observed in the preoperative data . Both groups displayed significant improvements after surgery . However , we identified no significant differences between the 2 groups in the 2-year followup data for I-PSS ( International Prostate Symptom Score ) , quality of life scores or maximum flow rate values . Patients in the holmium laser enucleation group displayed a lower risk of hemorrhage , shorter bladder irrigation and catheter times , and shorter hospital stays . A larger amount of prostate tissue was retrieved in the holmium laser enucleation group , but the operation time was longer for this group than for the plasmakinetic Output:	Furthermore , there were no significant differences between lasers and bipolar technology in the maximum flow rate ( Qmax ) and international prostate symptom score ( IPSS ) at a minimum of 3 months after treatment . Complications , including urethral stricture , urinary incontinence , urinary tract infection , re-catheterization and blood transfusion , did not significantly differ between lasers and bipolar technology . Conclusion Early efficacy and safety profiles were comparable between bipolar and laser treatments . Differences were observed in terms of smaller reduction in Hb , shorter catheterization duration and shorter hospital stay in favor of lasers . However , the smaller reduction in Hb , with lasers , did not translate into reduced transfusion requirements .
MS212004	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background : Some individuals with moderate/severe persistent asthma develop irreversible airway obstruction . These individuals present with dyspnoea , exercise intolerance and impaired quality of life ( QOL ) , all of which could potentially be alleviated with exercise training . Objective : To investigate whether exercise training improves functional exercise capacity and QOL in middle-aged and older adults with fixed airway obstruction asthma ( FAOA ) . Methods : 35 subjects aged 67.8 ± 10.6 years , with FEV1 59 ± 16 % of predicted , were r and omised to a 6-week ‘ intervention ’ period of supervised exercise training ( n = 20 ) or usual care ( n = 15 ) . This period was preceded by a 3-week run-in period during which asthma control was assessed weekly . Functional exercise capacity ( 6-min walk distance , 6MWD ) and QOL ( Asthma QOL Question naire , AQLQ ) were measured before , immediately following and 3 months after the intervention period . Results : 34 subjects ( exercise group , n = 19 , and control group , n = 15 ) completed the intervention period . Relative to the control group , the exercise group had greater improvements immediately following and 3 months after the intervention in the AQLQ symptom domain ( 0.61 , p = 0.001 , and 0.57 points per item , p = 0.005 ) and AQLQ activity limitation domain ( 0.43 , p = 0.04 , and 0.55 points per item , p = 0.04 ) . 6MWD increased ( 36 ± 37 m , p < 0.01 ) in the exercise group immediately following training and remained elevated ( 34 ± 45 m , p < 0.01 ) at the 3-month follow-up . The magnitude of change in 6MWD between groups was not significant , despite no change in the control group . Conclusions : Supervised exercise training improves symptoms and QOL in adults with FAOA BACKGROUND Aerobic training has a number of well known beneficial effects in both normal and asthmatic children . However , the impact of training on the clinical management of the underlying bronchial asthma remains controversial , particularly in the most severe patients . METHODS Clinical evaluation , spirometric tests , symptom limited maximum exercise testing , and exercise challenge tests were performed in a group of children with stable moderate to severe asthma . Forty two patients ( 24 boys ) aged 8–16 were evaluated twice : before and after supervised aerobic training ( group 1 , n = 26 ) and two months apart ( untrained group 2 , n = 16 ) . RESULTS Spirometric and maximal exercise variables in the initial evaluation were significantly reduced in group 1 ( p<0.05 ) but medication and clinical scores and the occurrence of exercise induced bronchospasm ( EIB ) did not differ between the two groups . Aerobic improvement with training ( maximal oxygen uptake and /or anaerobic threshold increment > 10 % and 100 ml ) was inversely related to the baseline level of fitness and was independent of disease severity . Although the clinical score and the occurrence of EIB did not change after training , aerobic improvement was associated with a significant reduction in the medication score and the daily use of both inhaled and oral steroids ( p<0.05 ) . CONCLUSIONS Aerobic improvement with training in less fit asthmatic children is related to a short term decrease in the daily use of inhaled and oral steroids , independent of the severity of the disease Background . Supervised exercise leads to significant improvements in asthma control and quality -of-life in adults with partly controlled asthma ; however , the role of unsupervised exercise is unknown . Methods . The purpose of this study was to determine the impact of self-directed exercise on subjective and objective indices of asthma-related health . Participants ( n = 24 ) were assigned to an exercise group or a control group for a 12-week period . Those in the exercise group were provided with exercise programs by a qualified exercise professional . These programs were up date d through electronic mail every 3 weeks to ensure progression . Controls maintained their current lifestyle habits for the intervention period . Assessment s of aerobic fitness , lung function , and subjective and objective asthma measures were conducted at baseline and after completion of the 12-week intervention period for both groups . Analysis of covariance was used to detect differences between groups from baseline to week 12 . Qualitative analyses were used to assess responses to open-ended questions . Results . Adherence to the program was poor . Perceived asthma control and self-reported frequency and severity of asthma improved significantly in the exercise group at week 12 compared with that in the control group . Objective measures of asthma such as asthma control , quality -of-life , and lung function , as well as peak and submaximal aerobic fitness did not change relative to controls . Responses to open-ended questions revealed improvements in three areas : asthma management , perceived fitness , and well-being . Conclusion . Adults with partly controlled asthma are able to improve perceived control and subjective measures of asthma-related health with 12 weeks of self-directed exercise ; however , supervision may be required to make significant improvements to measured asthma control , quality of life , and aerobic fitness . Future research should focus on the means to improve adherence of self-directed exercise programs in this population The effect of two types of physical training on patients with perennial asthma were compared in a blind , controlled , r and omized study . Eleven of 27 adults with asthma performed a physical training programme which did not change their oxygen consumption ( control group ) . The remaining 16 asthmatics performed a physical training programme which improved their maximal oxygen consumption ( training group ) . Both of the training programmes were performed for 1 hour , twice a week during a period of 2 months . No complications were reported during the performance of the training programmes . The doses of all medicines apart from beta 2-agonist aerosol were unchanged during the training period . The patients inhaled beta 2-agonist aerosol if their peak expiratory flow ( PEF ) was less than 60 % of their maximal PEF . The training group decreased their use of aerosol from an average of 4.94 puffs per day to 3.41 puffs per day ( P less than 0.05 ) . The control group did not change their use of beta 2-agonist aerosol significantly . It is concluded that physical exercise which improves the maximal oxygen consumption decreases the use of beta 2-agonist spray and that heavy exercise is well tolerated by asthmatics The present multicentre study evaluates the differences in efficacy between a 3 month rehabilitation programme including drug treatment , and a 3 month control period of drug treatment only , for asthmatic patients and patients with chronic obstructive pulmonary disease ( COPD ) . The programme was run by physiotherapists in eight local practice s , and included exercise training , patient education , breathing retraining , evacuation of mucus , relaxation techniques , and recreational activities . In a r and omized controlled trial with a cross-over design , the effects of rehabilitation were evaluated 3 and 6 months after baseline measurements in terms of exercise tolerance and quality of life ( QOL ) . Exercise tolerance was assessed using submaximal cycle ergometer tests and 6 min walking tests . QOL was evaluated by means of the Chronic Respiratory Disease Question naire ( CRDQ ) . After 3 months , the patients who started with rehabilitation showed significant improvements in endurance time ( 421 s ) and cardiac frequency ( 6 beats.min-1 ) during cycling , walking distance ( 39 m ) , and total CRDQ score ( 17 points ) compared to the control group . These improvements were still significant after 6 months . Additional analysis indicated that the asthmatic patients and the patients with COPD responded to rehabilitation in a similar way , with the exception that there was a greater improvement in walking distance for asthmatics . Improvements in exercise tolerance were not significantly correlated with improvements in QOL . Rehabilitation of patients with asthma or chronic obstructive pulmonary disease in local physiotherapy practice s improves exercise tolerance and quality of life The effects of a 3-month physical training programme on airway inflammation and clinical outcomes were studied in school-aged children with asthma . Subjects with persistent allergic asthma ( aged 12.7±3.4 yrs ; n = 34 ) were r and omly allocated into training and control groups . Exercise consisted of twice-weekly 50-min sessions for 12 weeks . Inflammation was assessed by levels of exhaled nitric oxide , blood eosinophils , eosinophil cationic protein , C-reactive protein , and total and mite-specific immunoglobulin (Ig)E. Lung volumes and bronchial responsiveness to methacholine were determined . The Paediatric Asthma Quality of Life Question naire and Paediatric Asthma Caregiver 's Quality of Life Question naire were used to evaluate activity restrictions , symptoms and emotional stress . The efficacy of the training was assessed by accelerometry . Following the programme , the exercise group spent twice as much time as the controls undertaking moderate-to-vigorous activities . No differences in changes were seen between groups for asthma outcomes . However , total IgE decreased more in the exercise group , as did mite-specific IgE. Training did not increase inflammation in children with persistent asthma , and may have decreased both total and allergen-specific immunoglobulin E levels . It is concluded that there is no reason to discourage asthmatic children with controlled disease to exercise Fitness improvement was used to compare morning with afternoon exercise periods for asthmatic children . Children with persistent moderate asthma ( according to GINA criteria ) , 8 to 11 years old , were divided into 3 groups : morning training group ( N = 23 ) , afternoon training group ( N = 23 ) , and non-training group ( N = 23 ) . The program was based on twice a week 90-min sessions for 4 months . We measured the 9-min running distance , resting heart rate and abdominal muscle strength ( sit-up number ) before and after the training . All children took budesonide , 400 microg/day , and an on dem and inhaled ss-agonist . The distance covered in 9 min increased ( mean + /- SEM ) from 1344 + /- 30 m by 248 + /- 30 m for the morning group , from 1327 + /- 30 m by 162 + /- 20 m for the afternoon group , and from 1310 + /- 20 m by 2 + /- 20 m for the control group ( P < 0.05 for the comparison of morning and afternoon groups with the control group by ANOVA and P > 0.05 for morning with afternoon comparison ) . The reduction of resting heart rate from 83 + /- 1 , 85 + /- 2 and 86 + /- 1 bpm was 5.1 + /- 0.8 bpm in the morning group , 4.4 + /- 0.8 bpm in the afternoon group , and -0.2 + /- 0.7 bpm in the control group ( P > 0.05 for morning with afternoon comparison and P < 0.05 versus control ) . The number of sit-ups in the morning , afternoon and control groups increased from 22.0 + /- 1.7 , 24.3 + /- 1.4 and 23 + /- 1.1 sit-ups by 9.8 + /- 0.9 , 7.7 + /- 1.4 , and 1.9 + /- 0.7 sit-ups , respectively ( P > 0.05 for morning with afternoon comparison and P < 0.05 versus control ) . No statistically significant differences were detected between the morning and afternoon groups in terms of physical training of asthmatic children OBJECTIVE To assess the effect of a training protocol on aerobic and anaerobic fitness in children with asthma . STUDY DESIGN Sixteen boys ( mean age : 13 years ; range : 10 - 16 years ) with mild-to-moderate asthma participated in a rehabilitation program that included 6 weeks of individualized training on a cycle ergometer . Two groups were r and omly formed : the control group ( CG , n = 7 ) and the training group ( TG , n = 9 ) , which exercised at an intensity set at the heart rate corresponding to the ventilatory threshold , with 1-minute sprints against the maximal aerobic power ( MAP ) every 4 minutes . Session duration was 45 minutes , 3 sessions per week . Changes in maximal oxygen uptake ( VO(2)max ) , MAP , short-term peak power ( PP ) , and pulmonary function were assessed . RESULTS Two patients of the training group did not complete the study . Pulmonary function remained unchanged in both groups . Improvement in both aerobic and anaerobic fitness was significant only in the training group ( TG vs CG ) : VO(2)max + 18 % + /- 2.1 % versus + 9 % + /- 4.5 % ( P < .05 ) , MAP + 32 % + /- 5 % versus 12 % + /- 7 % ( P < .05 ) , PP + 21 % + /- 5.7 % versus + 8.8 % + /- 10 % ( P < .01 ) . CONCLUSION Exercise training with high-intensity bouts is well tolerated in children with mild-to-moderate asthma . When included in a global rehabilitation program , this type of training improves both aerobic and anaerobic fitness . Anaerobic activities should be considered in sports rehabilitation programs for children with asthma Twenty-six adults ( 23 to 58 years ) with mild to moderate asthma underwent a 10-week supervised rehabilitation program , with emphasis on physical training . In the first 2 weeks , they exercised daily in an indoor Output:	Physical training was well tolerated with no adverse effects reported . None of the studies mentioned worsening of asthma symptoms following physical training . This review demonstrated that physical training can improve cardiopulmonary fitness and was well tolerated among people with asthma in the included studies .
MS212005	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The authors evaluated a coeducational program for teenagers on preventing sexual coercion in dating situations . Students examined individual and social attitudes underlying coercive sexual behavior and learned communication skills aim ed at preventing or dealing with unwanted sexual advances . Instruction was enhanced by video and an interactive video " virtual date . " Outcomes were assessed using sexual attitude scales with a sample of 458 high school students . Student health education classes were r and omly assigned to either a treatment or a control condition . Findings , based on a latent variable model of differential effectiveness , showed that students in the treatment group with initial coercive attitude scores at or above the mean benefited significantly more than students with the same range of scores in the control group Motivational interviewing is a brief non-confrontational intervention design ed to enhance motivation to reduce harmful behavior ( Miller and Rollnick 2002 ) . The purpose of this study was to examine the effectiveness of motivational interviewing as a targeted prevention approach for partner aggression in emerging adulthood . Participants were 50 college dating couples between 18 and 25 years old who reported at least one act of male-to-female physical aggression in their current relationships . After completing a 2-hour assessment session , half of all couples were r and omly assigned to a 2-hour individualized motivational feedback session targeting physical aggression and risk factors for aggression . The remaining couples received minimal , non-motivational feedback . Follow-up surveys were conducted 3 , 6 , and 9 months later . Hierarchical linear modeling analyses indicated that , compared to the control condition , the motivational feedback intervention led to reductions in physical aggression and harmful alcohol use and to less acceptance of female psychological aggression and male psychological aggression ( among women only ) . Lagged analyses indicated that changes in physical aggression were predicted by reductions in psychological aggression and by lower acceptance of both male and female psychological aggression . Reductions in physical aggression predicted lower anxiety and greater relationship investment and male relationship commitment over time . These findings suggest that a brief motivational intervention is a useful prevention approach for high-risk dating couples , with benefits to both individual and relationship functioning OBJECTIVES This study assessed the effects of the Safe Date s program on the primary and secondary prevention of adolescent dating violence . METHODS Fourteen schools were r and omly allocated to treatment conditions . Eighty percent ( n=1886 ) of the eighth and ninth grade rs in a rural county completed baseline question naires , and 1700 ( 90 % ) completed follow-up question naires . RESULTS Treatment and control groups were comparable at baseline . In the full sample at follow-up , less psychological abuse , sexual violence , and violence perpetrated against the current dating partner were reported in treatment than in control schools . In a sub sample of adolescents reporting no dating violence at baseline ( a primary prevention sub sample ) , there was less initiation of psychological abuse in treatment than in control schools . In a sub sample of adolescents reporting dating violence at baseline ( a secondary prevention sub sample ) , there was less psychological abuse and sexual violence perpetration reported at follow-up in treatment than in control schools . Most program effects were explained by changes in dating violence norms , gender stereotyping , and awareness of services . CONCLUSIONS The Safe Date s program shows promise for preventing dating violence among adolescents A study was undertaken to determine the effectiveness of a 5-session relationship violence prevention program involving a middle school of predominantly African-American students . A composite measure assessed changes in knowledge , attitudes , and methods of dealing with relationship violence . A pretest-posttest control group design was used . Results indicated that treatment group scores were significantly higher than control group scores at posttest ( p < .001 ) and treatment group posttest scores were significantly higher than pretest scores ( p < .001 ) . There were significant differences in scores between regular-level students and those with a higher level of academic ability ( advanced students ) . Within the treatment group , there was a level-by-gender interaction revealing that male advanced students made the highest gains . In examining specific items , improvements were made in knowledge about relationship violence and attitudes about nonphysical violence . No changes were seen in attitudes about physical violence or in methods of dealing with relationship violence OBJECTIVES This study determined 4-year postintervention effects of Safe Date s on dating violence , booster effects , and moderators of the program effects . METHODS We gathered baseline data in 10 schools that were r and omly allocated to a treatment condition . We collected follow-up data 1 month after the program and then yearly thereafter for 4 years . Between the 2- and 3-year follow-ups , a r and omly selected half of treatment adolescents received a booster . RESULTS Compared with controls , adolescents receiving Safe Date s reported significantly less physical , serious physical , and sexual dating violence perpetration and victimization 4 years after the program . The booster did not improve the effectiveness of Safe Date s. CONCLUSIONS Safe Date s shows promise for preventing dating violence but the booster should not be used This study evaluated a community-based intervention to help at-risk teens develop healthy , nonabusive relationships with dating partners . Participants were 158 14 - 16-year-olds with histories of child maltreatment who were r and omly assigned to a preventive intervention group or a no-treatment control group . They completed measures of abuse and victimization with dating partners , emotional distress , and healthy relationship skills at bimonthly intervals when dating someone . Intervention consisted of education about healthy and abusive relationships , conflict resolution and communication skills , and social action activities . Growth curve analyses showed that intervention was effective in reducing incidents of physical and emotional abuse and symptoms of emotional distress over-time . Findings support involvement of youths in reducing the cycle of violence as they initiate dating in midadolescence In this experiment , 123 sixth and seventh grade classrooms from Clevel and area schools were r and omly assigned to one of two five-session curricula addressing gender violence/sexual harassment ( GV/SH ) or to a no-treatment control . Three-student surveys were administered . Students in the law and justice curricula , compared to the control group , had significantly improved outcomes in awareness of their abusive behaviors , attitudes toward GV/SH and personal space , and knowledge . Students in the interaction curricula experienced lower rates of victimization , increased awareness of abusive behaviors , and improved attitudes toward personal space . Neither curricula affected perpetration or victimization of sexual harassment . While the intervention appeared to reduce peer violence victimization and perpetration , a conflicting finding emerged — the intervention may have increased dating violence perpetration ( or at least the reporting of it ) but not dating violence victimization This article summarizes the results of the Ohio University Sexual Assault Risk Reduction Project , which is a program design ed to reduce college women 's risk for sexual assault . The program was evaluated at 2 separate universities with 762 women . Participants were r and omly assigned either to the program or to the no-treatment comparison group , and they completed measures that assessed sexual victimization , dating behaviors , sexual communication , and rape empathy at the pretest and at the 2-month and 6-month follow-ups . At the 2-month follow-up , there were no differences between the groups on any of the outcome measures . However , those women who were moderately victimized during the 2-month follow-up were significantly less likely to be revictimized during the 6-month follow-up period if they participated in the program Men and women living in r and omly selected 1st-year dormitories participated in tailored single-sex sexual assault prevention or risk-reduction programs , respectively . An evaluation of the men ’s project is presented ( N = 635 ) . The program incorporated social norms and byst and er intervention education and had an impact on self-reported sexual aggression and an effect on men ’s perceptions that their peers would intervene when they encountered inappropriate behavior in others . Relative to the control group , participants also reported less reinforcement for engaging in sexually aggressive behavior , reported fewer associations with sexually aggressive peers , and indicated less exposure to sexually explicit media Fast Track is a multisite , multicomponent preventive intervention for young children at high risk for long-term antisocial behavior . Based on a comprehensive developmental model , intervention included a universal-level classroom program plus social skills training , academic tutoring , parent training , and home visiting to improve competencies and reduce problems in a high-risk group of children selected in kindergarten . At the end of Grade 1 , there were moderate positive effects on children 's social , emotional , and academic skills ; peer interactions and social status ; and conduct problems and special-education use . Parents reported less physical discipline and greater parenting satisfaction/ease of parenting and engaged in more appropriate/consistent discipline , warmth/positive involvement , and involvement with the school . Evidence of differential intervention effects across child gender , race , site , and cohort was minimal Abstract Objective : To investigate possible risk factors and mechanisms behind the four times higher and diverging mortality from coronary heart disease in Lithuanian compared with Swedish middle aged men . Design : Concomitant cross sectional comparison of r and omly selected 50 year old men without serious acute or chronic disease . Methods and equipment were identical or highly st and ardised between the centres . Setting : LinkÖping ( Sweden ) and Vilnius ( Lithuania ) . Subjects : 101 and 109 men aged 50 in LinkÖping and Vilnius respectively . Main outcome measures : Anthropometric data , blood pressure , smoking , plasma lipid and lipoprotein concentrations , susceptibility of low density lipoprotein to oxidation , and plasma concentrations of fat soluble antioxidant vitamins . Results : Systolic blood pressure was higher ( 141v 133 mm Hg , P<0.01 ) , smoking habits were similar , and plasma total cholesterol ( 5.10 v 5.49 mmol/l , P<0.01 ) and low density lipoprotein cholesterol ( 3.30 v 3.68 mmol/l , P<0.01 ) lower in men from Vilnius compared with those from LinkÖping . Triglyceride , high density lipoprotein cholesterol , and Lp(a ) lipoprotein concentrations did not differ between the two groups . The resistance of low density lipoprotein to oxidation was lower in the men from Vilnius ; lag phase was 67.6 v 79.5 minutes ( P<0.001 ) . Also lower in the men from Vilnius were mean plasma concentrations of lipid soluble antioxidant vitamins ( ß carotene 377v 510 nmol/l , P<0.01 ; lycopene 327 v 615 nmol/l , P<0.001 ; and lipid adjusted tocopherol 0.25v 0.46 µmol/mmol , P<0.001 . Tocopherol concentration did not differ ) . Regression analysis showed that the lag phase was still significantly shorter by 10 minutes in men from Vilnius when the influence of other known factors was taken into account . Conclusions : The high mortality from coronary heart disease in Lithuania is not caused by traditional risk factors alone . Mechanisms related to antioxidant state may be important . Key messages Mortality from coronary heart disease in 50 - 54 year old men is four times higher in Lithuania than in Sweden Differences in traditional risk factors for coronary heart disease in 50 year old men in LinkÖping ( Sweden ) and Vilnius ( Lithuania ) were small – systolic blood pressure was higher in men from Vilnius , but total and low density lipoprotein cholesterol concentrations were lower and smoking habits similar The resistance of low density lipoprotein to oxidation was lower in men from Vilnius and remained after adjustment for antioxidant vitamin concentrations Plasma concentrations of the antioxidant vitamins , ß carotene , lycopene , and lipid adjusted tocopherol were lower in men from Vilnius ; tocopherol did not differ Mechanisms related to antioxidant state may be important in explaining the much higher mortality from coronary heart disease in Lithuanian compared with Swedish middle aged A r and omized controlled trial , using parent-based intervention ( PBI ) was design ed to reduce the incidence of alcohol-involved sexual victimization among first-year college students . The PBI , adapted from Turrisi et al. ( 2001 ) , was design ed to increase alcohol-specific and general communication between mother and daughter . Female graduating high school seniors and their mothers were recruited from the community and r and omly assigned to one of four conditions : Alcohol PBI ( n = 305 ) , Enhanced Alcohol + Sex PBI ( n = 218 ) , Control ( n = 288 ) or Unmeasured Control ( n = 167 ) . Mothers in the intervention conditions were provided an informational h and book and encouraged to discuss its contents with their daughters prior to college matriculation . Consistent with hypotheses , PBI , either st and ard or enhanced , was associated with lower incidence of incapacitated rape in the first year of college relative to controls . Path analysis revealed support for a hypothesized indirect effects model , by which intervention increased mother-daughter communication , which predicted lower frequency of first semester heavy episodic drinking , result ing in lower rates of alcohol-involved sexual victimization in the first year of college The Safe Date s Project is a r and omized trial for evaluating a school-based adolescent dating violence prevention program . Five waves of data were used to examine the effects of Safe Date s over time including primary and secondary prevention effects , moderators , and mediators of program effects . Using r and om coefficients models , with multiple imputation of missing data , significant program effects were found at all four follow-up periods on psychological , moderate physical , and sexual dating violence perpetration and moderate physical dating violence victimization . Marginal effects were found on sexual victimization . Effects on severe physical perpetration at all four follow-up periods were moderated by prior involvement in that type of violence . Primary and secondary prevention effects were Output:	Subgroup analyses showed no statistically significant differences by intervention setting or type of participants . Studies included in this review showed no evidence of effectiveness of interventions on episodes of relationship violence or on attitudes , behaviours and skills related to relationship violence . We found a small increase in knowledge but there was evidence of substantial heterogeneity among studies .
MS212006	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Although , as yet , there is no specific treatment of epidermolysis bullosa ( EB ) simplex , anecdotal reports suggest the possible efficacy of one of the newer topical nonsteroidal anti-inflammatory agents , bufexamac . To determine whether bufexamac has any role in the management of this disease , a double-blind placebo-controlled crossover clinical trial was undertaken with ten patients ( nine , Weber-Cockayne variant ; one , generalized EB simplex ) . Each of the two preparations was applied four times daily during the 2 four-week treatment periods . Weekly assessment s included counts of blisters , crusts , and erosions , and assessment s of alterations in cutaneous pain , healing times , and activity times before further blister formation . Although considerable variability in individual responses was noted , no significant difference was detectable between the active drug and its matched placebo . On the basis of these findings , it was concluded that 5 % topical bufexamac is ineffective in the treatment of EB simplex BACKGROUND Recessive dystrophic epidermolysis bullosa is an uncommon , severely disabling , heritable disorder characterized by abnormal fragility of the skin . Open trials have suggested that phenytoin is an effective treatment , and this therapy is now widely used . METHODS To determine the efficacy of phenytoin in the treatment of recessive dystrophic epidermolysis bullosa , we performed a r and omized , double-blind , placebo-controlled , crossover trial in 36 patients . Each treatment was given for five to seven months , separated by a two-month period . We measured the total number of blisters and erosions on the entire body , the size of three plaques containing blisters and erosions , and the number of blisters and erosions in the three plaques at the beginning and end of each treatment period in each patient . RESULTS Twenty-two patients completed both courses of therapy , seven patients completed one course , and seven patients withdrew before completing a single course . There was no significant difference in disease activity between phenytoin treatment and placebo treatment , as measured by changes in the number of blisters and erosions on the entire body ( 7 percent decrease vs. 6 percent increase ) , in the area of three design ated plaques ( 0.4 percent decrease vs. 0.2 percent increase ) , or in the number of blisters and erosions in the design ated plaques ( 12 percent decrease vs. 31 percent increase ) . CONCLUSIONS Phenytoin is not an effective treatment for patients with recessive dystrophic epidermolysis bullosa Output:	There is no reliable trial evidence for interventions in inherited EB .
MS212007	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Interferon-based treatment is not suitable for many patients with hepatitis C virus ( HCV ) infection because of contraindications such as psychiatric illness , and a high burden of adverse events . We assessed the efficacy and safety of an interferon-free regimen -- a fixed-dose combination of the nucleotide polymerase inhibitor sofosbuvir ( 400 mg ) and the HCV NS5A inhibitor ledipasvir ( 90 mg ) , with and without ribavirin -- in patients with genotype-1 hepatitis C infection who were treatment-naive or previously treated with a protease-inhibitor regimen . METHODS For this open-label study , we enrolled 100 adult patients ( > 18 years ) with HCV infection at a centre in the USA between Nov 2 , 2012 , and Dec 21 , 2012 . In cohort A , we used a computer-generated sequence to r and omly assign ( 1:1:1 ; stratified by HCV genotype [ 1a vs 1b ] ) 60 non-cirrhotic , treatment-naive patients to receive sofosbuvir plus ledipasvir for 8 weeks ( group 1 ) , sofosbuvir plus ledipasvir and ribavirin for 8 weeks ( group 2 ) , or sofosbuvir plus ledipasvir for 12 weeks ( group 3 ) . In cohort B , we r and omly allocated ( 1:1 ; stratified by genotype and presence or absence of cirrhosis ) 40 patients who previously had virological failure after receiving a protease inhibitor regimen to receive sofosbuvir plus ledipasvir for 12 weeks ( group 4 ) or sofosbuvir plus ledipasvir and ribavirin for 12 weeks ( group 5 ) . 22 ( 55 % ) of 40 patients in cohort B had compensated cirrhosis . The primary endpoint was sustained virological response 12 weeks after treatment ( SVR12 ) , analysed by intention to treat . This study is registered with Clinical Trials.gov , number NCT01329978 . FINDINGS In cohort A , SVR12 was achieved by 19 ( 95 % ) of 20 patients ( 95 % CI 75 - 100 ) in group 1 , by 21 ( 100 % ) of 21 patients ( 84 - 100 ) in group 2 , and by 18 ( 95 % ) of 19 patients ( 74 - 100 ) in group 3 . In cohort B , SVR12 was achieved by 18 ( 95 % ) of 19 patients ( 74 - 100 ) in group 4 and by all 21 ( 100 % ) of 21 patients ( 84 - 100 ) in group 5 . Two patients had viral relapse ; one patient was lost to follow-up after achieving sustained virological response 8 weeks after treatment . The most common adverse events were nausea , anaemia , upper respiratory tract infection , and headache . One patient in group five had a serious adverse event of anaemia , thought to be related to ribavirin treatment . INTERPRETATION These findings suggest that the fixed-dose combination of sofosbuvir-ledipasvir alone or with ribavirin has the potential to cure most patients with genotype-1 HCV , irrespective of treatment history or the presence of compensated cirrhosis . Further clinical trials are needed to establish the best treatment duration and to further assess the contribution of ribavirin . FUNDING Gilead Sciences Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more BACKGROUND The phase 2 C-SALVAGE study ( Hepatitis C-Salvage Study for Patients who Failed DAA/PR Therapy ) demonstrated a 96.2 % sustained virologic response at 12 weeks ( SVR12 ) rate using the NS3/4A protease inhibitor grazoprevir and the NS5A inhibitor elbasvir together with ribavirin in treatment-experienced patients with chronic hepatitis C virus ( HCV ) genotype 1 infection . METHODS C-SALVAGE was a prospect i ve open-label trial of grazoprevir 100 mg once daily and elbasvir 50 mg once daily coadministered with weight-based ribavirin twice daily for 12 weeks in genotype 1-infected cirrhotic and noncirrhotic patients who had failed treatment with ≥ 4 weeks of pegylated interferon and ribavirin plus either boceprevir , telaprevir , or simeprevir . Although the primary efficacy outcome was SVR12 , patients were also evaluated 24 weeks after cessation of study therapy . Population sequencing was performed at baseline and periodically in virologic failures throughout the 24-week posttherapy follow-up period . RESULTS SVR24 rates were 76 of 79 ( 96.2 % ) overall , with all 3 relapses occurring by posttherapy week 8 . Every NS3 and NS5A variant detected at baseline reappeared at the time of relapse and persisted throughout the available follow-up period . NS3_A156 T emerged in virus from each patient at relapse , but rapidly disappeared over the ensuing 2 weeks in 2 patients . NS5A_Y93H emerged in virus from 2 patients at relapse and persisted for the entire follow-up period . CONCLUSIONS Grazoprevir and elbasvir with ribavirin for 12 weeks maintained HCV suppression for at least 24 weeks posttherapy without late relapses . Baseline resistance-associated variants ( RAVs ) stably reappeared at relapse in all 3 patients with virologic failure . NS5A_RAVs emerging at relapse persisted for the full 24-week follow-up period . If confirmed , this finding could complicate retreatment of the small number of patients failing regimens containing an NS5A inhibitor . CLINICAL TRIALS REGISTRATION NCT02105454 BACKGROUND Effective treatment for hepatitis C virus ( HCV ) genotype 1 infection in patients who have not had a sustained virologic response to prior interferon-based therapy represents an unmet medical need . METHODS We conducted a phase 3 , r and omized , open-label study involving patients infected with HCV genotype 1 who had not had a sustained virologic response after treatment with peginterferon and ribavirin , with or without a protease inhibitor . Patients were r and omly assigned to receive the NS5A inhibitor ledipasvir and the nucleotide polymerase inhibitor sofosbuvir in a once-daily , fixed-dose combination tablet for 12 weeks , ledipasvir-sofosbuvir plus ribavirin for 12 weeks , ledipasvir-sofosbuvir for 24 weeks , or ledipasvir-sofosbuvir plus ribavirin for 24 weeks . The primary end point was a sustained virologic response at 12 weeks after the end of therapy . RESULTS Among the 440 patients who underwent r and omization and were treated , 20 % had cirrhosis and 79 % had HCV genotype 1a infection . The rates of sustained virologic response were high in all treatment groups : 94 % ( 95 % confidence interval [ CI ] , 87 to 97 ) in the group that received 12 weeks of ledipasvir-sofosbuvir ; 96 % ( 95 % CI , 91 to 99 ) in the group that received 12 weeks of ledipasvir-sofosbuvir and ribavirin ; 99 % ( 95 % CI , 95 to 100 ) in the group that received 24 weeks of ledipasvir-sofosbuvir ; and 99 % ( 95 % CI , 95 to 100 ) in the group that received 24 weeks of ledipasvir-sofosbuvir and ribavirin . No patient discontinued treatment owing to an adverse event . The most common adverse events were fatigue , headache , and nausea . CONCLUSIONS Treatment with a once-daily , single-tablet regimen of ledipasvir and sofosbuvir result ed in high rates of sustained virologic response among patients with HCV genotype 1 infection who had not had a sustained virologic response to prior interferon-based treatment . ( Funded by Gilead Sciences ; ION-2 Clinical Trials.gov number , NCT01768286 . ) A new class of highly potent NS5A inhibitors with an unsymmetric benzimidazole-difluorofluorene-imidazole core and distal [2.2.1]azabicyclic ring system was discovered . Optimization of antiviral potency and pharmacokinetics led to the identification of 39 ( ledipasvir , GS-5885 ) . Compound 39 ( GT1a replicon EC50 = 31 pM ) has an extended plasma half-life of 37 - 45 h in healthy volunteers and produces a rapid > 3 log viral load reduction in monotherapy at oral doses of 3 mg or greater with once-daily dosing in genotype 1a HCV-infected patients . 39 has been shown to be safe and efficacious , with SVR12 rates up to 100 % when used in combination with direct-acting antivirals having complementary mechanisms BACKGROUND Compared with other countries , patients with chronic hepatitis C infection in Japan tend to be older , have more advanced liver disease , and are more likely to have been previously treated for hepatitis C. We aim ed to assess the efficacy and safety of an all-oral , fixed-dose combination of the hepatitis C virus NS5A inhibitor ledipasvir and the NS5B nucleotide polymerase inhibitor sofosbuvir with and without ribavirin for 12 weeks in treatment-naive and previously treated Japanese patients with chronic genotype 1 hepatitis C virus infection . METHODS In this r and omised , open-label study , we enrolled patients from 19 clinical Japanese centres . Patients were r and omly assigned ( 1:1 ) to receive either ledipasvir ( 90 mg ) and sofosbuvir ( 400 mg ) or ledipasvir , sofosbuvir , and ribavirin ( dosed according to the Japanese Copegus product label-ie , patients ≤60 kg received 600 mg daily , patients > 60 kg to ≤80 kg received 800 mg daily , and patients > 80 kg received 1000 mg daily ) orally once daily for 12 weeks . After completion or early discontinuation of treatment , patients were followed up off-treatment for 24 weeks . Eligible patients were at least 20 years of age with chronic genotype 1 hepatitis C virus infection with serum hepatitis C virus RNA concentrations of at least 5 log10 IU/mL , creatinine clearance of at least 1·0 mL/s , and a platelet count of at least 50 × 10(9 ) per L. An interactive web response system was used to manage patient r and omisation and treatment assignment . R and omisation was stratified by the presence or absence of cirrhosis for treatment-naive patients and stratified by presence or absence of cirrhosis and by previous treatment category ( relapser or breakthrough , non-responder , or interferon-intolerant ) for previously treated patients . Within each strata , patients were sequentially assigned to either treatment with ledipasvir-sofosbuvir or ledipasvir-sofosbuvir plus ribavirin in a 1:1 ratio with block size of 4 . The primary endpoint was sustained virological response 12 weeks after completion of treatment ( SVR12 ) assessed in all patients who were r and omly assigned and received at least one dose of study drug ; safety outcomes were assessed in all patients who received at least one dose of study drug . This trial is registered with Clinical Trials.gov , number NCT01975675 . FINDINGS Between Oct 15 , 2013 and Dec 13 , 2013 , 341 patients were r and omly assigned to treatment groups and received at least one dose of study treatment . SVR12 was achieved in all 171 ( 100 % ) patients ( 83 of 83 treatment naive and 88 of 88 treatment experienced ) receiving ledipasvir-sofosbuvir ( 95 % CI 98 - 100 ) and 167 ( 98 % ) of 170 patients ( 80 of 83 treatment naive and 87 of 87 treatment experienced ) receiving ledipasvir-sofosbuvir plus ribavirin ( 95 % CI 95 - 100 ) . Of the 76 patients with baseline NS5A resistant variants , 75 ( 99 % ) achieved SVR12 . Two ( 1·2 % ) of 170 patients in the ledipasvir-sofosbuvir plus ribavirin group discontinued treatment because of adverse events . The most common adverse events were nasopharyngitis ( 50 [ 29·2 % ] of 171 ) , headache ( 12 [ 7·0 % ] of 171 ) , and malaise ( nine [ 5·3 % ] of 171 ) in patients receiving ledipasvir-sofosbuvir ; and nasopharyngitis ( 40 [ 23·5 % ] of 1 Output:	Our findings suggest that 12 weeks of SOF/LDV can not be considered noninferior to 12 weeks of SOF/LDV/RBV to achieve SVR12 in patients with CHC who have cirrhosis and failed prior therapy
MS212008	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Interest in the chemopreventive effects of the trace element selenium has spanned the past three decades . Of > 100 studies that have investigated the effects of selenium in carcinogen-exposed animals , two-thirds have observed a reduction in tumor incidence and /or preneoplastic endpoints ( G. F. Combs and S. B. Combs , The Role of Selenium in Nutrition Chapter 10 , pp . 413 - 462 . San Diego , CA : Academic Press , 1986 , and B. H. Patterson and O. A. Lev and er , Cancer Epidemiol . Biomark . Prev . , 6 : 63 - 69 , 1997 ) . The Nutritional Prevention of Cancer Trial , a r and omized clinical trial reported by Clark et al. ( L. C. Clark et al. , JAMA , 276 : 1957 - 1963 , 1996 ) , showed as a secondary end point , a statistically significant decrease in lung cancer incidence with selenium supplementation . The adjusted hazard ratio ( HR ) was 0.56 [ 95 % confidence interval ( CI ) , 0.31 - 1.01 ; P = 0.05 ] . These results were based on active follow-up of 1312 participants . This re analysis used an extended Nutritional Prevention of Cancer Trial participant follow-up through the end of the blinded clinical trial on February 1 , 1996 . The additional 3 years added 8 cases to the selenium-treated group and 4 cases to the placebo group , and increased follow-up to 7.9 years . The relative risk of 0.70 ( 95 % CI , 0.40 - 1.21 ; P = 0.18 ) is not statistically significant . Whereas the overall adjusted HR is not significant ( HR = 0.74 ; 95 % CI , 0.44 - 1.24 ; P = 0.26 ) , and the HR for current and former smokers was not significant , the trend is toward a reduction in risk of incident lung cancer with selenium supplementation . In a subgroup analysis there was a nominally significant HR among subjects with baseline plasma selenium in the lowest tertile ( HR = 0.42 ; 95 % CI , 0.18 - 0.96 ; P = 0.04 ) . The analysis for the middle and highest tertiles of baseline showed HRs of 0.91 and 1.25 . The current re analysis indicates that selenium supplementation did not significantly decrease lung cancer incidence in the full population , but a significant decrease among individuals with low baseline selenium concentrations was observed Controlled trials that use r and omized allocation are the best tool to control for bias and confounding in trials testing clinical interventions . Investigators must be sure to include information that is required by the reader to judge the validity and implication s of the findings in the reports of these trials . In part , complete reporting of trials will allow clinicians to modify their clinical practice to reflect current evidence toward the improvement of clinical outcomes . The consoli date d st and ards of reporting trials ( CONSORT ) statement was developed to assist investigators , authors , review ers , and editors on the necessary information to be included in reports of controlled clinical trials . The CONSORT statement is applicable to any intervention , including herbal medicinal products . Controlled trials of herbal interventions do not adequately report the information suggested in CONSORT . Recently , reporting recommendations were developed in which several CONSORT items were elaborated to become relevant and complete for r and omized controlled trials of herbal medicines . We expect that these recommendations will lead to more complete and accurate reporting of herbal trials . We wrote this explanatory document to outline the rationale for each recommendation and to assist authors in using them by providing the CONSORT items and the associated elaboration , together with examples of good reporting and empirical evidence , where available , for each . These recommendations for the reporting of herbal medicinal products presented here are open to revision as more evidence accumulates and critical comments are collected BACKGROUND Brazil nuts provide a rich natural source of selenium , yet no studies have investigated the bioavailability of selenium in humans . OBJECTIVE We investigated the efficacy of Brazil nuts in increasing selenium status in comparison with selenomethionine . DESIGN A r and omized controlled trial was conducted with 59 New Zeal and adults . Participants consumed 2 Brazil nuts thought to provide approximately 100 mug Se , 100 mug Se as selenomethionine , or placebo daily for 12 wk . Actual intake from nuts averaged 53 mug Se/d ( possible range : 20 - 84 mug Se ) . Plasma selenium and plasma and whole blood glutathione peroxidase ( GPx ) activities were measured at baseline and at 2 , 4 , 8 , and 12 wk , and effects of treatments were compared . RESULTS Plasma selenium increased by 64.2 % , 61.0 % , and 7.6 % ; plasma GPx by 8.3 % , 3.4 % , and -1.2 % ; and whole blood GPx by 13.2 % , 5.3 % , and 1.9 % in the Brazil nut , selenomethionine , and placebo groups , respectively . Change over time at 12 wk in plasma selenium ( P < 0.0001 for both groups ) and plasma GPx activity in the Brazil nut ( P < 0.001 ) and selenomethionine ( P = 0.014 ) groups differed significantly from the placebo group but not from each other . The change in whole blood GPx activity was greater in the Brazil nut group than in the placebo ( P = 0.002 ) and selenomethionine ( P = 0.032 ) groups . CONCLUSION Consumption of 2 Brazil nuts daily is as effective for increasing selenium status and enhancing GPx activity as 100 mug Se as selenomethionine . Inclusion of this high-selenium food in the diet could avoid the need for fortification or supplements to improve the selenium status of New Zeal and ers This pilot study evaluated the feasibility and effectiveness of conducting a double-blind clinical trial for the prevention of lung cancer with selenium ( Se ) in Yunnan Tin Corporation , the People 's Republic of China , where the incidence rates of lung cancer are extraordinarily high among the miners . Forty healthy miners were r and omized to either 300 μg of Se in high Se malt cakes or an identical placebo of malt cakes daily for one year . Subjects consumed their usual daily diet . The low Se concentrations in plasma ( 0.05±0.008 μg/mL ) and hair ( 0.442±0.085 μg/g ) reflected their low dietary Se intake in the control subjects . In Se-supplemented group , the Se status was increased by 178 % for serum and 194.8 % for hair . The serum GSHpx activity was increased by 155.7 % , whereas the lipid peroxide level was reduced by 74.5 % compared to the placebo . The results of UDS assay indicated that the lymphocyte DNA damage induced by ultraviolet irradiation and carcinogen 3,4-benzpyrene could be protected by Se supplementation . Se-supplementation did not affect the liver function test ( SGPT ) , as well as the concentrations of hemoglobin , albumin , and cholesterol . Thus , daily intake of 300 μg Se in form of Se-malt as a chemopreventive measure is safe and effective to humans with low Se status The Nutritional Prevention of Cancer Trial was a r and omized , clinical trial design ed to evaluate the efficacy of selenium as selenized yeast ( 200 microg daily ) in preventing the recurrence of nonmelanoma skin cancer among 1312 residents of the Eastern United States . Original secondary analyses through December 31 , 1993 showed striking inverse associations between treatment and the incidence of total [ hazard ratio ( HR ) = 0.61 , 95 % confidence interval ( CI ) = 0.46 - 0.82 ] , lung , prostate , and colorectal cancer and total cancer mortality . This report presents results through February 1 , 1996 , the end of blinded treatment . Effect modification by baseline characteristics is also evaluated . The effects of treatment overall and within subgroups of baseline age , gender , smoking status , and plasma selenium were examined using incidence rate ratios and Cox proportional hazards models . Selenium supplementation reduced total ( HR = 0.75 , 95 % CI = 0.58 - 0.97 ) and prostate ( HR = 0.48 , 95 % CI = 0.28 - 0.80 ) cancer incidence but was not significantly associated with lung ( HR = 0.74 , 95 % CI = 0.44 - 1.24 ) and colorectal ( HR = 0.46 , 95 % CI = 0.21 - 1.02 ) cancer incidence . The effects of treatment on other site-specific cancers are also described . The protective effect of selenium was confined to males ( HR = 0.67 , 95 % CI = 0.50 - 0.89 ) and was most pronounced in former smokers . Participants with baseline plasma selenium concentrations in the lowest two tertiles ( < 121.6 ng/ml ) experienced reductions in total cancer incidence , whereas those in the highest tertile showed an elevated incidence ( HR = 1.20 , 95 % CI = 0.77 - 1.86 ) . The Nutritional Prevention of Cancer trial continues to show a protective effect of selenium on cancer incidence , although not all site-specific cancers exhibited a reduction in incidence . This treatment effect was restricted to males and to those with lower baseline plasma selenium concentrations Nonexperimental studies suggest that individuals with higher selenium ( Se ) status are at decreased risk of cancer . The Nutritional Prevention of Cancer ( NPC ) study r and omized 1,312 high-risk dermatology patients to 200-mcg/day of Se in selenized yeast or a matched placebo ; selenium supplementation decreased the risk of lung , colon , prostate , and total cancers but increased the risk of nonmelanoma skin cancer . In this article , we report on a small sub study in Macon , GA , which began in 1989 and r and omized 424 patients to 400-mcg/day of Se or to matched placebo . The subjects from both arms had similar baseline Se levels to those treated by 200 mcg , and those treated with 400-mcg attained plasma Se levels much higher than subjects treated with 200 mcg . The 200-mcg/day Se treatment decreased total cancer incidence by a statistically significant 25 % ; however , 400-mcg/day of Se had no effect on total cancer incidence Summary □ Patients and Method : In order to test the hypothesis that a dietary supplement of selenium ( Se ) may reduce cancer risk , 1312 patients with histories of basa/squamous cell carcinomas of the skin were assigned in r and om , double-blind fashion to daily oral supplements of either Se-enriched yeast ( 200 µg Se/day ) , or a low-Se yeast placebo . Patients were recruited in 1983 to 1990 and were followed with regular dermatologic examinations through , 1993 for a total of 8269 person-years of observation . Skin cancer diagnoses were confirmed histologically and plasma Se concentration was determined at 6 to 12 months intervals . All deaths and patient-reported illnesses were confirmed and documented by consultation with the patient medical care providers . □ Results : Results showed that Se-supplementation did not significantly affect the incidences of recurrent basal/squamous cell carcinomas of the skin . However , Se-treatment was associated with reductions in total cancer mortality and in the incidences of lung , colorectal , prostate and total cancers . These effects were consistent over time and between study clinics . □ Conclusion : The results strongly suggest benefits of Se-supplementation for this cohort of patients and support the hypothesis that supplemental Se can reduce risks to at least some types of cancer Purpose We conducted a phase I study to determine the recommended dose of selenomethionine ( SLM ) in combination with irinotecan that consistently results in a protective plasma selenium ( Se ) concentrations > 15 μM after 1 week of SLM loading . Experimental Design A 3 - 3 st and ard escalation design was followed . SLM was given orally twice daily ( BID ) for one week ( loading ) followed by continuous once daily ( QD ) dosing ( maintenance ) . Seven dose levels of selenomethionine were investigated . Irinotecan was given intravenously at a fixed st and ard weekly dose , starting on the first day of maintenance SLM . Results Thirty-one patients were treated on study . Dose limiting diarrhea complicated by sepsis was noted in one of six patients at each of the dose-levels 1 and 7 . Dose-levels ≥ 5 ( 4,800 mcg/dose loading maintenance ) result ed in day 8 Se concentrations > 15 μM while dose-level 7 ( 7,200 mcg/dose loading and maintenance ) result ed in day 8 Se concentrations > 20 μM. No significant variations in SN-38 or biliary index were noted between weeks 1 and 4 of treatment . Despite achieving target Se concentrations , gastrointestinal and bone marrow toxicities were common and irinotecan dose modification was prevalent . Objective responses were seen in two patients and nine patients had disease control for 6 months or longer . Conclusions Selenomethionine can be escalated safely to 7,200 mcg BID Output:	In the treatment of lung cancers , selenium may reduce cisplatin-induced nephrotoxicity and side effects associated with radiation therapy . CONCLUSIONS Selenium may be effective for lung cancer prevention among individuals with lower selenium status , but at present should not be used as a general strategy for lung cancer prevention .
MS212009	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The clinical question at issue , whether it is possible to combine implants and natural teeth via fixed bridges , is of current interest . The treatment of the subjects of this prospect i ve study was performed between June 1984 and December 1986 . This article presents the 5-year results of the study . The consecutive patient material comprised 23 patients with Applegate Kennedy Class I residual dentition in the m and ible and a complete maxillary denture . All 23 patients were provided with implants ad modum Brånemark in each m and ibular quadrant . One side was r and omized to rehabilitation with fixed bridge between the distal tooth of the residual dentition and an implant ; the other side received a free-st and ang bridge on 2 implants . The fixture survival rate was 88 % . No difference was found between the two sides . Bridge stability was 89 % for the implant bridges and 91 % for the combination bridges . The change in marginal bone level at the implants was small during the 5-year follow up period ( on average 0.1 - 0.3 mm ) and with no difference between the two sides . In conclusion , it was not possible to demonstrate any higher risk of implant or prosthetic failure for tooth-implant fixed bridges compared with implant-supported bridges This study conducted a longitudinal prospect i ve clinical study of the single-crystal sapphire ( Al2O3 ) cylindrical screw-shaped endosteal dental implant , and attempted to establish clinical parameters to evaluate implant success or failure . Twenty-eight m and ibular implants ( 17 patients ) were placed . After six weeks ' healing , 23 implants in 15 patients served as distal abutments for fixed prostheses ( baseline ) . Implants were evaluated for bleeding index , crevicular fluid volume index , plaque accumulation index , radiographic index , mobility index , and patient comfort . Any implant failing in three of these criteria or implants removed were judged as failures . After 10 years , of the 21 baseline implants recalled ( two implants were lost to recall ) , 17 were fully functional , for an 81 % success rate . The use of qualitative and quantitative clinical evaluation parameters as utilized in this study appears to be important and useful in assessment s of the clinical serviceability of dental implants . These parameters can be used in human clinical trials as well as in experimental animal studies PURPOSE The use of implants for prosthetic rehabilitation of partially edentulous patients is increasing . However , the possibilities of placing implants in the posterior part of the m and ible are often limited . The purpose of this longitudinal study with 10 years of follow-up was to evaluate the use of short implants supporting fixed partial dentures ( FPD ) in the posterior part of the m and ible , and to compare implant supported FPDs to tooth-implant supported FPDs . MATERIAL S AND METHODS The patient material comprised 23 patients with residual m and ibular anterior teeth , and each patient received FPDs unilaterally . On one side the FPD was supported by two implants , and on the other side by one implant and one tooth , thus permitting intraindividual comparison . The distribution of the two types of FPDs in each jaw was r and omized . Implant success rates , marginal bone changes , and mechanical complications were studied . RESULTS The tooth-implant connection did not demonstrate any negative influences on the overall success rates for the 10-year period , nor were the shorter implants found to be less favorable . CONCLUSION It is suggested that a prosthetic construction supported by both a tooth and an implant may be recommended as a predictable and reliable treatment alternative in the posterior m and ible OBJECTIVES To assess prospect ively over 10 years the incidences of technical and /or biological complications and failures occurring in a cohort of consecutive partially edentulous patients with fixed reconstructions on implants of the ITI Dental Implant System . METHODS Eighty-nine patients were available , 34 ( 38.2 % ) were male , 55 ( 61.8 % ) were female . At the 10-year examination ( range 8 - 12 years ) , they were 58.9 years old ( range 28 - 88 years ) . RESULTS Single crowns ( SC ) : 48 patients had been restored with 69 SC on 69 implants . Five of the implants with the crowns were lost because of biological failures . Two crowns ( 2.9 % ) were remade because of technical failures . Total failure amounted to seven ( 10 % ) . Implant borne fixed partial dentures ( I-I FPD ) : In 29 patients who had been restored with 33 implant borne suprastructures , the total number of failed I-I FPD was 2 ( 6.1 % ) . Tooth-implant borne fixed partial dentures ( I-T FPD ) : In 21 patients , 22 mixed tooth-implant borne reconstructions were constructed . The number of failed FPD reached 7 ( 31.8 % ) . Statistically significantly fewer biological failures occurred with I-I FPD compared with the I-T FPDs ( ANOVA , Bonferroni , P=0.022 ) . The I-T FPDs experienced statistically significantly more frequent technical failures compared with the other two groups of suprastructures ( P=0.003 , 0.031 ) . Consequences of complications : The occurrence of loss of retention as a complication increased the odds ratio ( OR ) to 17.6 ( P<0.001 ) to end up in a technical failure . Similarly , the event of a porcelain fracture increased the OR for the suprastructure to be a failure at 10 years to 11.0 ( P < or = 0.004 ) . Treatment of periimplantitis increased the OR to 5.44 ( P < or = 0.011 ) to result in a biological failure compared with implants in which this type of treatment was not applied . CONCLUSION The three groups of suprastructures demonstrated marked differences in their patterns of failures and complications . Complications increased the risk for failure . Support by CRF , University of Berne , Switzerl and PURPOSE This long-term follow-up study aim ed to compare the outcome of fixed prostheses supported by teeth and implants and by freest and ing implants only . MATERIAL S AND METHODS From prosthesis insertion up to 14 years ( mean 6.5 y ) , 18 patients were followed . Implant-supported prostheses with and without tooth connection were compared within the same jaw . The tooth-implant prostheses were supported by 30 implants and 30 teeth , and the freest and ing prostheses were supported by 48 implants . Implant outcome , marginal bone stability , and mechanical complications were recorded . RESULTS Neither implant mobility nor fractures of any component of the implants were observed . No prosthesis complications were observed , and the same applied for crown cement failure and intrusion of teeth . Only one periapical lesion was detected at the first follow up . The annual change of the marginal bone level around connected and freest and ing implants did not differ significantly . The mean marginal bone loss ( over the 2 groups ) for the first 6 months amounted to 1.08 mm . After the first 6 months , an annual marginal bone loss of 0.015 mm was observed . There was no difference between the 3 connection types ( single implant connected to single tooth , multiple implants and /or multiple teeth connected with single connector , and multiple connectors ) for the first 6 months or thereafter . The marginal bone loss ( over the 3 groups ) for the first 6 months was 1.15 mm . After the first 6 months , the annual bone loss ( over the 3 groups ) amounted to 0.015 mm . CONCLUSION Based on the results of this study , splinting teeth with implants for implant-supported fixed prostheses did not affect the long-term outcome in comparison to freest and ing implants In 123 patients , 339 implants were connected to 313 teeth by means of fixed partial prostheses ( test ) and followed up for 1.5 - 15 years ( mean : 6.5 ) . In another ad r and om selected 123 patients , 329 implants were connected to each other by means of 123 freest and ing fixed partial prostheses ( control ) and were followed up for 1.3 - 14.5 years ( mean : 6.2 ) . The aim of this study was to compare both treatment modalities with each other based on implant , tooth and prosthesis complications . The cumulative implant success , based on implant immobility and /or lack of implant fractures after loading , in the test and control groups amounted to 95 % and 98.5 % , respectively . Although in the test group 10 implants versus only 1 in the control group failed , a regression analysis of the survival data , based on the cox proportional hazards model , revealed no significant difference . In the test group periapical lesions ( 3.5 % ) , tooth fracture ( 0.6 % ) and tooth extraction due to fatal decay or periodontitis ( 1 % ) were observed , besides tooth intrusion ( 3.4 % ) and crown cement failure ( 8 % ) . Framework fracture occurred in 3 patients . In the control group , only 2 abutment screws fractured . The treatment of partial edentulism by means of oral implants was beneficial for our patients . Because of a clear tendency of more implant failures ( mobility or fractures ) and tooth complications in the tooth-implant connected prostheses , the freest and ing solution is the primary option to be considered . To avoid intrusion of abutment teeth , the connection , if made , should be completely rigid Intramobile cylinder ( IMZ ) implants with either of two coatings , hydroxyapatite ( HA ) or titanium plasma-flame ( TPF ) , as distal abutments for combined tooth implant-supported restorations , were compared in 313 partially edentulous m and ibles with respect to postprosthetical failure patterns and complication frequencies in a r and omized multicenter clinical trial . Within the treatment protocol s , the two coatings do not show evidence of different efficacy with respect to occurrence of postprosthetical integration deficiency ( ID ) or functional deficiency ( FD ) . Statistical equivalence for an absolute effect of + /-15 % in event-free survival could only be demonstrated for FD , not for ID , however . Intent-to-treat and per- protocol population analyses gave consistent results . Hazards of occurrence of ID and FD , adjusted for years of follow-up , were estimated for ID as 7 % per year ( 95%CI 4 - 10 % per year ) with HA and 5 % per year ( 95%CI 3 - 7 % per year ) with TPF , and for FD as 5 % per year ( 95%CI 3 - 7 % per year ) with HA and 4 % per year ( 95%CI 2 - 6 % per year ) with TPF . The 5-year cumulative success rates for no ID were 69.5 % ( 95%CI 58 - 81 % ) with HA and 82.2 % ( 95%CI 74 - 91 % ) with TPF . With respect to frequencies of complications , there was no relevant statistically significant difference between the two coatings 49 patients participated in a prospect i ve study of treatment of total or partial edentulism with fixed prosthodontics supported by Bioceram sapphire implants . 15 patients were treated for maxillary or m and ibular edentulism , and 7 for a missing maxillary anterior tooth . The remaining 27 patients , with Applegate-Kennedy Class I-IV residual dentitions , were treated with fixed bridges supported by free-st and ing implants , or bridges supported by teeth and implants . Implant success , prosthesis stability , radiographic marginal bone level as well as parameters for peri-implant health were evaluated . The study began in 1982 , and clinical treatment of the last patients was completed in 1988 , i.e. , a follow-up period ranging from 7 to 13 years . Of the patients treated for total m and ibular edentulism , one implant fractured after 6 years in situ . The bone implant score ( BIS ) values for those implants were at the time for the bridge cementation 63.5 + /- 1.4 and at 1 , 2 , 3 and 5 year follow-ups 62.1 + /- 1.4 , 61.9 + /- 1.5 , 61.5 + /- 1.6 , and 60.95 + /- 1.3 , respectively . The success rate was 100 % , 100 % and 97.7 % for the m and ible at 3 , 5 and 10 years , respectively . Of the 7 edentulous patients treated with maxillary fixed bridges , 6 implants in 1 patient had to be removed after 1 year in service . Another 2 patients lost all their implants , 6 each , after 36 months . 6 implants in the 4th patient did not fulfil the criteria for success and were rated as failures at the four year follow-up . The success rate was thus 58.1 % , 44.2 % and 44.2 % for the maxilla at 3 , 5 and 10 year follow-ups , respectively . Of the 7 patients in whom single missing teeth were replaced , 1 implant in the premolar region was lost during the 1st year post-operatively , but no other complications or changes in BIS were observed . Of the 27 patients treated for partial edentulism ( 56 implants total ) 1 implant , of a 4-unit free st and ing maxillary bridge fractured after 6 years and was later replaced . There were no statistically significant differences in BIS changes for the implants when used as abutments for partial maxillary or m and ibular edentulism . The cumulative success rates for the impl Output:	Despite a high survival of FPDs , biological and technical complications are frequent . This , in turn , means that substantial amounts of chair time have to be accepted by the clinician following the incorporation of implant-supported FPDs .
MS212010	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVES The aim of this prospect i ve r and omized study was to assess the impact of renal artery denervation in patients with a history of refractory atrial fibrillation ( AF ) and drug-resistant hypertension who were referred for pulmonary vein isolation ( PVI ) . BACKGROUND Hypertension is the most common cardiovascular condition responsible for the development and maintenance of AF . Treating drug-resistant hypertension with renal denervation has been reported to control blood pressure , but any effect on AF is unknown . METHODS Patients with a history of symptomatic paroxysmal or persistent AF refractory to ≥2 antiarrhythmic drugs and drug-resistant hypertension ( systolic blood pressure > 160 mm Hg despite triple drug therapy ) were eligible for enrolment . Consenting patients were r and omized to PVI only or PVI with renal artery denervation . All patients were followed ≥1 year to assess maintenance of sinus rhythm and to monitor changes in blood pressure . RESULTS Twenty-seven patients were enrolled , and 14 were r and omized to PVI only , and 13 were r and omized to PVI with renal artery denervation . At the end of the follow-up , significant reductions in systolic ( from 181 ± 7 to 156 ± 5 , p < 0.001 ) and diastolic blood pressure ( from 97 ± 6 to 87 ± 4 , p < 0.001 ) were observed in patients treated with PVI with renal denervation without significant change in the PVI only group . Nine of the 13 patients ( 69 % ) treated with PVI with renal denervation were AF-free at the 12-month post-ablation follow-up examination versus 4 ( 29 % ) of the 14 patients in the PVI-only group ( p = 0.033 ) . CONCLUSIONS Renal artery denervation reduces systolic and diastolic blood pressure in patients with drug-resistant hypertension and reduces AF recurrences when combined with PVI Renal sympathetic hyperactivity is seminal in the maintenance and progression of hypertension . Catheter-based renal sympathetic denervation has been shown to significantly reduce blood pressure ( BP ) in patients with hypertension . Durability of effect beyond 1 year using this novel technique has never been reported . A cohort of 45 patients with resistant hypertension ( systolic BP ≥160 mm Hg on ≥3 antihypertension drugs , including a diuretic ) has been originally published . Herein , we report longer-term follow-up data on these and a larger group of similar patients subsequently treated with catheter-based renal denervation in a nonr and omized manner . We treated 153 patients with catheter-based renal sympathetic denervation at 19 centers in Australia , Europe , and the United States . Mean age was 57±11 years , 39 % were women , 31 % were diabetic , and 22 % had coronary artery disease . Baseline values included mean office BP of 176/98±17/15 mm Hg , mean of 5 antihypertension medications , and an estimated glomerular filtration rate of 83±20 mL/min per 1.73 m2 . The median time from first to last radiofrequency energy ablation was 38 minutes . The procedure was without complication in 97 % of patients ( 149 of 153 ) . The 4 acute procedural complications included 3 groin pseudoaneurysms and 1 renal artery dissection , all managed without further sequelae . Postprocedure office BPs were reduced by 20/10 , 24/11 , 25/11 , 23/11 , 26/14 , and 32/14 mm Hg at 1 , 3 , 6 , 12 , 18 , and 24 months , respectively . In conclusion , in patients with resistant hypertension , catheter-based renal sympathetic denervation results in a substantial reduction in BP sustained out to ≥2 years of follow-up , without significant adverse events BACKGROUND Renal sympathetic hyperactivity is associated with hypertension and its progression , chronic kidney disease , and heart failure . We did a proof-of-principle trial of therapeutic renal sympathetic denervation in patients with resistant hypertension ( ie , systolic blood pressure > /=160 mm Hg on three or more antihypertensive medications , including a diuretic ) to assess safety and blood-pressure reduction effectiveness . METHODS We enrolled 50 patients at five Australian and European centres ; 5 patients were excluded for anatomical reasons ( mainly on the basis of dual renal artery systems ) . Patients received percutaneous radiofrequency catheter-based treatment between June , 2007 , and November , 2008 , with subsequent follow-up to 1 year . We assessed the effectiveness of renal sympathetic denervation with renal noradrenaline spillover in a subgroup of patients . Primary endpoints were office blood pressure and safety data before and at 1 , 3 , 6 , 9 , and 12 months after procedure . Renal angiography was done before , immediately after , and 14 - 30 days after procedure , and magnetic resonance angiogram 6 months after procedure . We assessed blood-pressure lowering effectiveness by repeated measures ANOVA . This study is registered in Australia and Europe with Clinical Trials.gov , numbers NCT 00483808 and NCT 00664638 . FINDINGS In treated patients , baseline mean office blood pressure was 177/101 mm Hg ( SD 20/15 ) , ( mean 4.7 antihypertensive medications ) ; estimated glomerular filtration rate was 81 mL/min/1.73m(2 ) ( SD 23 ) ; and mean reduction in renal noradrenaline spillover was 47 % ( 95 % CI 28 - 65 % ) . Office blood pressures after procedure were reduced by -14/-10 , -21/-10 , -22/-11 , -24/-11 , and -27/-17 mm Hg at 1 , 3 , 6 , 9 , and 12 months , respectively . In the five non-treated patients , mean rise in office blood pressure was + 3/-2 , + 2/+3 , + 14/+9 , and + 26/+17 mm Hg at 1 , 3 , 6 , and 9 months , respectively . One intraprocedural renal artery dissection occurred before radiofrequency energy delivery , without further sequelae . There were no other renovascular complications . INTERPRETATION Catheter-based renal denervation causes substantial and sustained blood-pressure reduction , without serious adverse events , in patients with resistant hypertension . Prospect i ve r and omised clinical trials are needed to investigate the usefulness of this procedure in the management of this condition BACKGROUND Activation of renal sympathetic nerves is key to pathogenesis of essential hypertension . We aim ed to assess effectiveness and safety of catheter-based renal denervation for reduction of blood pressure in patients with treatment-resistant hypertension . METHODS In this multicentre , prospect i ve , r and omised trial , patients who had a baseline systolic blood pressure of 160 mm Hg or more ( ≥150 mm Hg for patients with type 2 diabetes ) , despite taking three or more antihypertensive drugs , were r and omly allocated in a one-to-one ratio to undergo renal denervation with previous treatment or to maintain previous treatment alone ( control group ) at 24 participating centres . R and omisation was done with sealed envelopes . Data analysers were not masked to treatment assignment . The primary effectiveness endpoint was change in seated office-based measurement of systolic blood pressure at 6 months . Primary analysis included all patients remaining in follow-up at 6 months . This trial is registered with Clinical Trials.gov , number NCT00888433 . FINDINGS 106 ( 56 % ) of 190 patients screened for eligibility were r and omly allocated to renal denervation ( n=52 ) or control ( n=54 ) groups between June 9 , 2009 , and Jan 15 , 2010 . 49 ( 94 % ) of 52 patients who underwent renal denervation and 51 ( 94 % ) of 54 controls were assessed for the primary endpoint at 6 months . Office-based blood pressure measurements in the renal denervation group reduced by 32/12 mm Hg ( SD 23/11 , baseline of 178/96 mm Hg , p<0·0001 ) , whereas they did not differ from baseline in the control group ( change of 1/0 mm Hg [ 21/10 ] , baseline of 178/97 mm Hg , p=0·77 systolic and p=0·83 diastolic ) . Between-group differences in blood pressure at 6 months were 33/11 mm Hg ( p<0·0001 ) . At 6 months , 41 ( 84 % ) of 49 patients who underwent renal denervation had a reduction in systolic blood pressure of 10 mm Hg or more , compared with 18 ( 35 % ) of 51 controls ( p<0·0001 ) . We noted no serious procedure-related or device-related complications and occurrence of adverse events did not differ between groups ; one patient who had renal denervation had possible progression of an underlying atherosclerotic lesion , but required no treatment . INTERPRETATION Catheter-based renal denervation can safely be used to substantially reduce blood pressure in treatment-resistant hypertensive patients . FUNDING Ardian Hypertension represents a significant global public health concern , contributing to vascular and renal morbidity , cardiovascular mortality , and economic burden . The opportunity to influence clinical outcomes through hypertension management is therefore paramount . Despite adherence to multiple available medical therapies , a significant proportion of patients have persistent blood pressure elevation , a condition termed resistant hypertension . Recent recognition of the importance of the renal sympathetic and somatic nerves in modulating blood pressure and the development of a novel procedure that selectively removes these contributors to resistant hypertension represents an opportunity to provide clinical ly meaningful benefit across wide and varied patient population s. Early clinical evaluation with catheter‐based , selective renal sympathetic denervation in patients with resistant hypertension has mechanistically correlated sympathetic efferent denervation with decreased renal norepinephrine spillover and renin activity , increased renal plasma flow , and has demonstrated clinical ly significant , sustained reductions in blood pressure . The SYMPLICITY HTN‐3 Trial is a pivotal study design ed as a prospect i ve , r and omized , masked procedure , single‐blind trial evaluating the safety and effectiveness of catheter‐based bilateral renal denervation for the treatment of uncontrolled hypertension despite compliance with at least 3 antihypertensive medications of different classes ( at least one of which is a diuretic ) at maximal tolerable doses . The primary effectiveness endpoint is measured as the change in office‐based systolic blood pressure from baseline to 6 months . This manuscript describes the design and methodology of a regulatory trial of selective renal denervation for the treatment of hypertension among patients who have failed pharmacologic therapy . Clin . Cardiol . 2012 . doi : Output:	CONCLUSIONS In conclusion , while poor quality unblinded studies provide evidence that renal denervation using catheter-based systems is effective in reducing systolic and diastolic blood pressure in resistant hypertension , the largest r and omised controlled trial to date ( SYMPLICITY HTN-3 ) failed to demonstrate any benefit
MS212011	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: PURPOSE The study assesses potential for improving residents ' evidence -based medicine search ing skills in MEDLINE through real-time librarian instruction . SUBJECTS Ten residents on a rotation in a neonatal intensive care unit participated . METHODOLOGY Residents were r and omized into an instruction and a non-instruction group . Residents generated questions from rounds and search ed MEDLINE for answers . Data were collected through observation , search strategy analysis , and surveys . Librarians observed search es and collected data on questions , search ing skills , search problems , and the test group 's instruction topics . Participants performed st and ardized search es before , after , and six-months after intervention and were scored using a search strategy analysis tool ( 1 representing highest score and 5 representing lowest score ) . Residents completed pre- and post-intervention surveys to measure opinions about MEDLINE and search satisfaction . RESULTS Post-intervention , the test group formulated better questions , used limits more effectively , and reported greater confidence in using MEDLINE . The control group expressed less satisfaction with retrieval and demonstrated more errors when limiting . The test and control groups had the following average search scores respectively : 3.0 and 3.5 ( pre-intervention ) , 3.3 and 3.4 ( post-intervention ) , and 2.0 and 3.8 ( six-month post-intervention ) . CONCLUSION Data suggest that measurable learning outcomes were achieved . Residents receiving instruction improved and retained search ing skills six-months after intervention BACKGROUND The " Just-in-time Information " ( JIT ) librarian consultation service was design ed to provide rapid information to answer primary care clinical questions during patient hours . This study evaluated whether information provided by librarians to answer clinical questions positively impacted time , decision-making , cost savings and satisfaction . METHODS AND FINDING A r and omized controlled trial ( RCT ) was conducted between October 2005 and April 2006 . A total of 1,889 questions were sent to the service by 88 participants . The object of the r and omization was a clinical question . Each participant had clinical questions r and omly allocated to both intervention ( librarian information ) and control ( no librarian information ) groups . Participants were trained to send clinical questions via a h and -held device . The impact of the information provided by the service ( or not provided by the service ) , additional re sources and time required for both groups was assessed using a survey sent 24 hours after a question was su bmi tted . The average time for JIT librarians to respond to all questions was 13.68 minutes/ question ( 95 % CI , 13.38 to 13.98 ) . The average time for participants to respond their control questions was 20.29 minutes/ question ( 95 % CI , 18.72 to 21.86 ) . Using an impact assessment scale rating cognitive impact , participants rated 62.9 % of information provided to intervention group questions as having a highly positive cognitive impact . They rated 14.8 % of their own answers to control question as having a highly positive cognitive impact , 44.9 % has having a negative cognitive impact , and 24.8 % with no cognitive impact at all . In an exit survey measuring satisfaction , 86 % ( 62/72 responses ) of participants scored the service as having a positive impact on care and 72 % ( 52/72 ) indicated that they would use the service frequently if it were continued . CONCLUSIONS In this study , providing timely information to clinical questions had a highly positive impact on decision-making and a high approval rating from participants . Using a librarian to respond to clinical questions may allow primary care professionals to have more time in their day , thus potentially increasing patient access to care . Such services may reduce costs through decreasing the need for referrals , further tests , and other courses of action . TRIAL REGISTRATION Controlled-Trials.com IS RCT N96823810 OBJECTIVE This article presents the results of complementary research studies on the behaviors of hospital clinicians in asking clinical questions and the relationship between asking of questions , outcome of information search es , and success in problem solving . METHODS Triangulation in research methods --a combination of mailed question naires , interviews , and a r and omized controlled study --was employed to provide complementary views of the research problems under study . RESULTS The survey and interviews found that clinical problems ( concerned mainly with therapy and equipment or technology ) were expressed as statements rather than questions ( average number of concepts = 1.7 ) , that only slightly more than half ( higher for doctors ) of problems could be solved , and that the majority of clinical questions were not well formed . An educational workshop however improved clinicians ' formulation of questions , but the use of structured prompting was found to improve building of hypotheses in the doctors ' group without training . The workshop also improved satisfaction with the obtained information and success in problem solving . Nonetheless , for both the experimental and control groups , more structured and complete questions or statements did not mean higher success rates in problem solving or higher satisfaction with obtained information . CONCLUSION The triangulation methods have gathered complementary evidence to reject the hypothesis that building well-structured clinical questions would mean higher satisfaction with obtained information and higher success in problem solving OBJECTIVE To determine the effectiveness of providing synthesized research evidence to inform patient care practice s via an evidence based informatics program , the Clinical Informatics Consult Service ( CICS ) . DESIGN Consults were r and omly assigned to one of two conditions : CICS Provided , in which clinicians received synthesized information from the biomedical literature addressing the consult question or No CICS Provided , in which no information was provided . MEASUREMENT Outcomes were measured via online post-consult forms that assessed consult purpose , actual and potential impact , satisfaction , time spent search ing , and other variables . RESULTS Two hundred twenty six consults were made during the 19-month study period . Clinicians primarily made requests in order to up date themselves ( 65.0 % , 147/226 ) and were satisfied with the service results ( Mean 4.52 of possible 5.0 , SD 0.94 ) . Intention to treat ( ITT ) analyses showed that consults in the CICS Provided condition had a greater actual and potential impact on clinical actions and clinician satisfaction than No CICS consults . Evidence provided by the service primarily impacted the use of a new or different treatment ( OR 8.19 95 % CI 1.04 - 64.00 ) . Reasons for no or little impact included a lack of evidence addressing the issue or that the clinician was already implementing the practice s indicated by the evidence . CONCLUSIONS Clinical decision-making , particularly regarding treatment issues , was statistically significantly impacted by the service . Programs such as the CICS may provide an effective tool for facilitating the integration of research evidence into the management of complex patient care and may foster clinicians ' engagement with the biomedical literature OBJECTIVE To determine if a preceptor and individualized feedback improves the performance of physicians in search ing MEDLINE in clinical setting s. DESIGN R and omized controlled trial with 2 to 10 months follow-up . SETTING A 300-bed teaching hospital . PARTICIPANTS All 392 physicians and physicians-in-training from 6 major clinical departments were invited to participate if they made patient-care decisions during the study period ; 79.4 % agreed . INTERVENTIONS All participants were given 2 hours of basic training , then r and omized to a control group ( no further intervention ) or an intervention group in which each person chose a clinical preceptor experienced in MEDLINE search ing and received individualized feedback from a study librarian on each of their 1st 10 search es . MAIN OUTCOME MEASURES The number and proportion of relevant and irrelevant references retrieved for 1st , 4th , and 8th search es of participants were compared with independent librarian search es on the same topics . RESULTS Intervention group members did not search more often than controls ( 5.9 search es per month versus 4.7 , respectively ; P = 0.26 ) and there were no significant differences in the quality of search es . Rather , search performance for both groups improved , with the average number of relevant references retrieved per search increasing from 4.5 to 7.4 ( P < 0.01 ) . The librarian retrieved more relevant citations than participants for the 1st search ( P = 0.001 ) but not for the 4th ( P = 0.60 ) or 8th ( P = 0.76 ) search es . CONCLUSIONS A program of assigning preceptors and providing feedback on individual search es did not enhance the quantity or quality of search es . Soon after a basic introduction to search ing , however , clinicians in both groups improved their search performance Background Cost consequences analysis was completed from r and omized controlled trial ( RCT ) data for the Just-in-time ( JIT ) librarian consultation service in primary care that ran from October 2005 to April 2006 . The service was aim ed at providing answers to clinical questions arising during the clinical encounter while the patient waits . Cost saving and cost avoidance were also analyzed . The data comes from eighty-eight primary care providers in the Ottawa area working in Family Health Networks ( FHNs ) and Family Health Groups ( FHGs ) . Methods We conducted a cost consequences analysis based on data from the JIT project [ 1 ] . We also estimated the potential economic benefit of JIT librarian consultation service to the health care system . Results The results show that the cost per question for the JIT service was $ 38.20 . The cost could be as low as $ 5.70 per question for a regular service . Nationally , if this service was implemented and if family physicians saw additional patients when the JIT service saved them time , up to 61,100 extra patients could be seen annually . A conservative estimate of the cost savings and cost avoidance per question for JIT was $ 11.55 . Conclusions The cost per question , if the librarian service was used at full capacity , is quite low . Financial savings to the health care system might exceed the cost of the service . Saving physician 's time during their day could potentially lead to better access to family physicians by patients . Implementing a librarian consultation service can happen quickly as the time required to train professional librarians to do this service is short A double-blind r and omised controlled trial was conducted on a group of Hong Kong hospital clinicians . The objective was to test if a three-hour educational workshop ( with supervised h and s-on practice ) is more effective ( than no training ) to improve clinical question formulation , information-seeking skills , knowledge , attitudes , and search outcomes . The design was a post-test-only control group ; recruitment by stratified r and omization ( by profession ) , blocked at 800 . End-user training was more effective than no training in improving clinical question formulation , in raising awareness , knowledge , confidence and use of data bases , but had made no impact on preference for secondary data bases . It changed the attitude of clinicians to become more positive towards the use of electronic information services ( EIS ) . Participants had higher search performance and outcomes ( satisfaction with information obtained ( NNT = 3 ) , EIS satisfaction ( NNT = 3 ) and success in problem solving ( NNT = 4 ) ) . The workshop improved knowledge and skills in evidence -based search ing , but this effect gradually eroded with time . Search logs confirmed that follow-up is required if effects are to be sustained . Longer effects on search behaviours appear to be positive . A r and omised controlled trial is valuable in identifying cause- and -effect relations and to quantify the magnitude of the effects for management decision-making This is a prospect i ve study of clinical questions generated in primary care consultations and a comparison of two approaches to answering those clinical questions . Twenty-one doctors in a university-based primary care clinic su bmi tted 78 clinical questions arising from patient consultations during 24 clinic days ( 0.01 question per patient encounter ) . These doctors subsequently found answers to 40 % of their questions but were satisfied with only 67 % of these answers . The investigators were able to provide answers for 95 % of the questions asked and the doctors rated these answers as satisfactory in 86 % of instances . Answers obtained by investigators had significantly higher satisfaction score than those obtained by doctors ' search ( p = 0.002 ) . The two main findings of this study are ( 1 ) almost all questions arising in clinic setting could be answered by intensive search ; ( 2 ) answers found by intensive search es were judged to be more satisfactory than those found routinely by doctors . Provision of an information retrieval service in addition to training in the search ing and appraisal of medical literature are possible solutions to the information needs of busy clinicians BACKGROUND Librarians at the University of Alberta have been involved with teaching undergraduate medical and dental education for several years . After 1 year of increased librarian involvement at the problem-based learning ( PBL ) , small-group level , informal feedback from faculty and students suggested that librarians ' participation in PBL groups was beneficial . There was , however , no real evidence to support this cl aim or justify the high dem and on librarians ' time . OBJECTIVES The study aim ed to determine whether having a librarian present in the small-group , problem-based learning modules for first-year medical and dental students results in an improved underst and ing of evidence -based medicine concepts , the nature of medical literature , and information access skills . METHODS One hundred and sixty-four first-year medical and dental students participated in the study . There were a total of 18 PBL groups , each with approximately nine students and one faculty tutor . Six librarians participated and were assigned r and omly to the six intervention groups . Students were given pre- and post-tests at the outset and upon completion of the 6-week course . RESULTS Post-test scores showed that there was a small positive librarian impact , but final exam scores showed no impact . There was also no difference in attitudes or comfort levels between students who had a librarian in their group and those who did not . CONCLUSIONS Impact was not sufficient to warrant continued participation of librarians in PBL . In future instruction , librarians at the John W. Scott Health Sciences Library will continue to teach at the larger group level AIM To compare the effectiveness of an online information literacy tutorial with a face-to-face session for teaching information literacy skills to nurses . DESIGN R and omised control trial Output:	No studies were found that investigated librarians providing direct services to research ers or patients in healthcare setting s. CONCLUSIONS Librarian-provided services directed to participants in training programs ( eg , students , residents ) improve skills in search ing the literature to facilitate the integration of research evidence into clinical decision-making . Services provided to clinicians were shown to be effective in saving time for health professionals and providing relevant information for decision-making . Two studies indicated patient length of stay was reduced when clinicians requested literature search es related to a patient 's case
MS212012	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND The efficacy and safety of testosterone treatment for hypoactive sexual desire disorder in postmenopausal women not receiving estrogen therapy are unknown . METHODS We conducted a double-blind , placebo-controlled , 52-week trial in which 814 women with hypoactive sexual desire disorder were r and omly assigned to receive a patch delivering 150 or 300 microg of testosterone per day or placebo . Efficacy was measured to week 24 ; safety was evaluated over a period of 52 weeks , with a subgroup of participants followed for an additional year . The primary end point was the change from baseline to week 24 in the 4-week frequency of satisfying sexual episodes . RESULTS At 24 weeks , the increase in the 4-week frequency of satisfying sexual episodes was significantly greater in the group receiving 300 microg of testosterone per day than in the placebo group ( an increase of 2.1 episodes vs. 0.7 , P<0.001 ) but not in the group receiving 150 microg per day ( 1.2 episodes , P=0.11 ) . As compared with placebo , both doses of testosterone were associated with significant increases in desire ( 300 microg per day , P<0.001 ; 150 microg per day , P=0.04 ) and decreases in distress ( 300 microg per day , P<0.001 ; 150 microg per day , P=0.04 ) . The rate of and rogenic adverse events - primarily unwanted hair growth - was higher in the group receiving 300 microg of testosterone per day than in the placebo group ( 30.0 % vs. 23.1 % ) . Breast cancer was diagnosed in four women who received testosterone ( as compared with none who received placebo ) ; one of the four received the diagnosis in the first 4 months of the study period , and one , in retrospect , had symptoms before undergoing r and omization . CONCLUSIONS In postmenopausal women not receiving estrogen therapy , treatment with a patch delivering 300 microg of testosterone per day result ed in a modest but meaningful improvement in sexual function . The long-term effects of testosterone , including effects on the breast , remain uncertain . ( Clinical Trials.gov number , NCT00131495 . INTRODUCTION A wide range of prevalence estimates of female sexual dysfunctions ( FSD ) have been reported . AIM Compare instruments used to assess FSD to determine if differences between instruments contribute to variation in reported prevalence . MAIN OUTCOME MEASURES Sexual Function Question naire combined with Female Sexual Distress Scale ( SFQ-FSDS ) was our gold st and ard , vali date d instrument for assessing FSD . Alternatives were SFQ alone and two sets of simple questions adapted from Laumann et al. 1994 . Methods . A postal survey was administered to a r and om sample of 356 Australian women aged 20 to 70 years . RESULTS When assessed by SFQ-FSDS , prevalence estimates ( 95 % confidence intervals ) of hypoactive sexual desire disorder , sexual arousal disorder ( lubrication ) , orgasmic disorder , and dyspareunia were 16 % ( 12 % to 20 % ) , 7 % ( 5 % to 11 % ) , 8 % ( 6 % to 12 % ) , and 1 % ( 0.5 % to 3 % ) , respectively . Prevalence estimates varied across alternative instruments for these disorders : 32 % to 58 % , 16 % to 32 % , 16 % to 33 % , and 3 % to 23 % , respectively . Compared with SFQ-FSDS alternative instruments produced higher estimates of desire , arousal and orgasm disorders and displayed a range of sensitivities ( 0.25 to 1.0 ) , specificities ( 0.48 to 0.99 ) , positive predictive values ( 0.01 to 0.56 ) , and negative predictive values ( 0.95 to 1.0 ) across the disorders investigated . Kappa statistics comparing SFQ-FSDS and alternative instruments ranged from 0 to 0.71 but were predominantly 0.44 or less . Changing recall from previous month to 1 month or more in the previous year produced higher estimates for all disorders investigated . Including sexual distress produced lower estimates for desire , arousal , and orgasm disorders . CONCLUSIONS Prevalence estimates of FSD varied substantially across instruments . Relatively low positive predictive values and kappa statistics combined with a broad range of sensitivities and specificities indicated that different instruments identified different subgroups . Consequently , the instruments research ers choose when assessing FSD may affect prevalence estimates and risk factors they report University of Illinois Thirty subjects seeking treatment for primary inorgasmia accompanied by sexual anxiety or aversion were assigned to one of three groups : systematic desensitization ( SD ) , directed masturbation ( DM ) , or waiting list control ( WL ) . Following treatment , subjects were retested , and the WL group then received directed masturbation treatment . A third testing constituted a follow-up for the SD and DM groups and a posttreatment testing for the WL . Both treatments were equally effective in improving subjects ' sexual self-acceptance and increasing sexual pleasure . Changes in anxiety were negligible ; however , sexual arousal and orgasm for DM and WL subjects increased . The gains of the WL group not only replicated the findings of the DM group but also were of greater magnitude Ginkgo biloba extract ( GBE ) facilitates blood flow , influences nitric oxide systems , and has a relaxant effect on smooth muscle tissue . These processes are important to the sexual response in women and , hence , it is feasible that GBE may have a therapeutic effect . The present study was the first to provide an empirical examination of the effects of both short- and long-term GBE administration on subjective and physiological ( vaginal photoplethysmography ) measures of sexual function in women with Sexual Arousal Disorder . A single dose of 300 mg GBE had a small but significant facilitatory effect on physiological , but not subjective , sexual arousal compared to placebo in 99 sexually dysfunctional women . The long-term effects of GBE on sexual function were assessed in 68 sexually dysfunctional women who were r and omly assigned to 8 weeks treatment of either ( 1 ) GBE ( 300 mg/daily ) , ( 2 ) placebo , ( 3 ) sex therapy which focused on training women to attend to genital sensations , or ( 4 ) sex therapy plus GBE . When combined with sex therapy , but not alone , long-term GBE treatment significantly increased sexual desire and contentment beyond placebo . Sex therapy alone significantly enhanced orgasm function compared with placebo . Long-term GBE administration did not significantly enhance arousal responses beyond placebo . It was concluded that ( 1 ) neither short- or long-term administration of GBE alone substantially impacts sexual function in women , ( 2 ) a substantial placebo effect on sexual function exists in women with sexual concerns , and ( 3 ) teaching women to focus on genital sensations during sex enhances certain aspects of women ’s sexual functioning This paper presents the results of a prospect i ve controlled study evaluating a programme of directed masturbation against a combined sensate focus and supportive psychotherapeutic approach in the management of female primary orgasmic failure . Of the 20 patients who followed the masturbation programme 90 per cent gained orgasmic capacity compared with 53 per cent of 15 patients who were treated conventionally . Eighty-five per cent of the patients treated by the masturbation programme and 47 per cent of the control group of patients became coitally orgasmic on at least 75 per cent of coital occasions . The difference is statistically significant at the 5 per cent level . The results suggest that directed masturbation is an effective adjunct in the management of primary female orgasmic failure BACKGROUND Oophorectomy reduces serum testosterone levels . We studied the efficacy and safety of transdermal testosterone in treating hypoactive sexual desire disorder in surgically menopausal women . METHODS A 24-week , r and omized , double-blind , placebo-controlled , parallel-group , multicenter trial was conducted in women ( aged 24 - 70 years ) who developed distressful low sexual desire after bilateral salpingo-oophorectomy and hysterectomy and who were receiving oral estrogen therapy . Women were r and omized to receive placebo ( n = 119 ) or testosterone patches in dosages of 150 microg/d ( n = 107 ) , 300 microg/d ( n = 110 ) , or 450 microg/d ( n = 111 ) twice weekly for 24 weeks . Sexual desire and frequency of satisfying sexual activity were primary efficacy outcome measures . RESULTS Of the 447 women r and omized , 318 ( 71 % ) completed the trial . Compared with placebo , women receiving the 300-microg/d testosterone patch had significantly greater increases from baseline in sexual desire ( 67 % vs 48 % ; P = .05 ) and in frequency of satisfying sexual activity ( 79 % vs 43 % ; P = .049 ) . The 150-microg/d group showed no evidence of a treatment effect . The 450-microg/d group also was not statistically different from the 300-microg/d or placebo groups . Marginally significant linear dose-response trends were observed for total satisfying sexual activity and sexual desire at 24 weeks ( P = .06 and .06 , respectively ) . Adverse events occurred with similar frequency in both groups ; no serious safety concerns were observed . CONCLUSIONS The 300-microg/d testosterone patch increased sexual desire and frequency of satisfying sexual activity and was well tolerated in women who developed hypoactive sexual desire disorder after surgical menopause Three components commonly utilized in sex therapy for secondary orgasmic dysfunction ( Sensate Focus I , Sensate Focus II , and ban on intercourse ) were studied , with the aim of not only exploring their effects on therapy outcome but also , in part , of sensitizing investigators to the benefits of incorporating component analyses within larger investigations of therapy outcome . The subjects were 23 married couples with the problem of secondary orgasmic dysfunction in the wife . Subjects were administered a multicomponent therapy program over a 14-week period . Daily self-monitoring data were analyzed to assess the impact of Sensate Focus exercises and banning intercourse on both broad ( e.g. , enjoyment ) and narrow ( e.g. , orgasmic response ) criteria of therapeutic effectiveness . Results indicated that for females , sensate focus exercises , in combination with a ban on intercourse , led to a significant increase in level of enjoyment for subsequent noncoital sexual caressing as well as intercourse . Orgasmic responsiveness , however , was not affected . The method ological issues of broad versus narrow therapeutic effects , compliance with treatment , and cost-effective techniques for the study of sex therapy components are discussed In an open study , sildenafil ( Viagra ) was prescribed for nine women out patients who reported sexual dysfunction induced by antidepressant medication , primarily selective serotonin reuptake inhibitors . A 50 mg dose of sildenafil was prescribed , and patients were instructed to take it approximately one hour before sexual activity . They were told to increase the dose to 100 mg on the next occasion if they experienced a partial response or a lack of response to sildenafil . The nine patients , all of whom had experienced either anorgasmia or delayed orgasm with or without associated disturbances , reported significant reversal of sexual dysfunction , usually with the first dose of 50 mg of sildenafil We conducted a double-blind , placebo-controlled study to determine the role of dietary supplementation on sexual function in women of differing menopausal status . One hundred eight ( 108 ) women , age 22–73 years , who reported a lack of sexual desire , enrolled as participants . Of these , 55 received ArginMax for women and 53 received placebo . ArginMax for women contains L-arginine , ginseng , ginkgo , damiana , multivitamins , and minerals . The 108 women , given definitions , self-reported as 59 premenopausal ( PRE ) ; 20 perimenopausal ( PERI ) , and 29 postmenopausal ( POST ) . After 4 weeks , PRE women on ArginMax primarily reported significant improvement in level of sexual desire ( 72 % ; p = 0.03 ) and satisfaction with overall sex life ( 68 % ; p = 0.007 ) , compared with placebo group , according to the Female Sexual Function Index ( FSFI ; Kaplan et al. , 1999 ) scales . Frequency of sexual desire ( 60 % ; p = 0.05 ) and frequency of intercourse ( 56 % p = 0.01 ) also increased among the PRE women . In contrast , among PERI women , primary improvements were reported for frequency of intercourse ( 86 % ; p = 0.002 ) , satisfaction with sexual relationship ( 79 % ; p = 0.03 ) , and vaginal dryness ( 64 % ; p = 0.03 ) compared with placebo group . POST women primarily showed an increased in level of sexual desire , with 51 % showing improvement , compared with only 8 % in the placebo group ( p = 0.008 ) . Nutritional intervention plays an important role in women 's sexual health , but issues and areas of greatest improvement differ among women of different menopausal states . The largest number of attribute improvements were seen in PRE and PERI women , although attribute types vary among these groups . Level of desire was shown to increase significantly in POST women . Since ArginMax for women has been shown to exhibit no estrogen activity , it may be desirable alternative to hormone therapy for sexual concerns Abstract Forty-eight couples complaining of secondary orgasmic Output:	Evidence -based , practice recommendations for the treatment of FOD are provided that will hopefully inform clinical decision making for those treating this common condition
MS212013	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Death rates of end-stage renal disease ( ESRD ) patients treated with hemodialysis vary substantially among treatment centers . The association between facility-to-facility differences in delivered hemodialysis dose and facility-specific mortality rates was examined among 5817 r and omly selected patients treated with hemodialysis on October 1 , 1994 , from all 213 hemodialysis treatment centers reporting to ESRD Network 6 . The mean urea reduction ratio ( URR ) for each treatment center , a measure of hemodialysis adequacy , was calculated for each facility , using measurements made by center staff members during one treatment for each of the r and omly selected patients . During 7 mo of follow-up ( ending April 30 , 1995 ) , 441 ( 7.6 % ) patients died . The average URR among the treatment centers was 64.9 % . There was a strong , inverse association between increasing treatment center URR and adjusted mortality count ( P = 0.009 ) . Other treatment center characteristics associated with increased mortality included free-st and ing status ( P = 0.009 ) and decreasing frequency of reported physician supervision of care ( P = 0.01 ) . It was concluded that lower average levels of dialysis adequacy in treatment centers are associated with higher rates of death , and this association persists after controlling for facility-to-facility differences in patient and nonpatient characteristics This historic prospect i ve study assessed the relationship between dialyzer reuse practice s and hemodialysis patient mortality through 1 year of follow-up . Medicare patient demographic and survival data were combined with dialyzer reuse data from the Centers for Disease Control and Prevention 's annual survey of dialysis-related diseases . Data were analyzed for the US Medicare hemodialysis population of never transplanted patients prevalent on January 1 , 1989 , and January 1 , 1990 , who were treated in freest and ing dialysis units that used primarily conventional ( not high-flux ) dialyzers . Time to mortality , or transplant , and other censoring on December 31st of each year was regressed with proportional hazards models on patient , dialysis unit , and reuse measures . Age- , race- , and diagnosis-st and ardized mortality ratios for dialysis units were also regressed with weighted least squares techniques against dialysis unit and reuse measures . The results showed that patients treated in dialysis units that disinfected dialyzers with a peracetic acid , hydrogen peroxide , acetic acid mixture , or glutaraldehyde experienced higher mortality than patients treated in units that used formalin or in units that did not reuse dialyzers . The relative risk of mortality , compared with patients treated in nonreuse dialysis units , was 1.17 ( P = 0.010 ) for glutaraldehyde and 1.13 ( P < 0.001 ) for the peracetic acid mixture . The relative risk for formalin compared with the reference group of nonreuse was 1.06 ( P = 0.088 ) . With adjustment for several patient and dialysis unit characteristics , dialyzer reuse with certain germicides was associated with a significantly elevated mortality risk . This elevated risk , the etiology of which is currently not known , may represent a large number of potentially avoidable deaths per year . Only a large , nationally based analysis of this type has sufficient sample size to detect mortality risks such as these We analyzed the effect of patient and dialysis unit characteristics on access to kidney transplantation using several different approaches , including an analysis of individual patient data from a systematic r and om sample of 2900 new dialysis patients from each year 1981 to 1985 ( 14721 patients total ) . Additional analyses focused on the composition of transplant waiting lists and aggregate data from a 1984 census of 1133 dialysis and transplant units . White , male , young , nondiabetic , high-income patients treated in smaller units are more likely to receive a cadaver transplant under Medicare than are other kidney patients . Profit status of the dialysis unit was not found to be correlated to access to transplantation , although size of the unit may be correlated to access . Future analysis should focus on whether patient access has been inappropriately compromised . Possible factors unexplored in this analysis include differential patient preferences and medical suitability , as well as differential medical access The diverse patient and dialysis unit characteristics in the United States pose challenges for assessing the safety and efficacy of reuse practice s. A 10 % r and om sample of period-prevalent hemodialysis patients from units practicing conventional dialysis ( < 25 % of patients with high-efficiency/high-flux dialysis ) were analyzed . The data included 13,926 patient observations in 1989 - 1990 and 20,422 in 1991 - 1993 . Centers for Disease Control and Prevention and Health Care Financing Administration facility survey Medicare data were analyzed with a Cox regression model , evaluating the risk of reuse compared with no reuse and adjusting for comorbidity , unit characteristics , and profit status . In 1989 - 1990 , freest and ing and hospital-based units that did not reuse dialyzers were not significantly different from each other in mortality rates . In 1991 - 1993 , however , no-reuse , freest and ing , for-profit units had higher risks ( relative risk [ RR ] = 1.23 , P = 0.003 ) compared with no-reuse , hospital-based , nonprofit units . No-reuse , hospital-based , for-profit units , in contrast , were associated with a lower mortality risk ( RR = 0.70 , P = 0.0001 ) . An isolated higher risk associated with peracetic acid manual reuse in freest and ing units ( 1989 - 1990 ) was identified in for-profit units only . In the 1991 - 1993 period , an increased mortality risk was noted in hospital-based , nonprofit units practicing formaldehyde automatic reuse , and in freest and ing , for-profit units using glutaraldehyde , which accounted for < 5 % of all units . All other interactions of reuse germicide and technique were not different from no-reuse . The varying mortality rates identified in both no-reuse and reuse units using conventional dialysis suggest that other factors , such as dialysis therapy and anemia correction ( both known predictors of patient survival ) , have a greater influence on U.S. mortality than reuse germicides and techniques Decrease in the average duration of hemodialysis treatment time is a continuing phenomenon . We investigated the relationship of 3-year mortality to duration of dialysis in a 1984 - 1985 national r and om sample of 600 hemodialysis patients from 36 dialysis units . Mortality was negatively associated with duration of dialysis treatments , as shown by the Cox model , adjusted for other patient and dialysis unit covariates . With adjustment for other covariates , patients receiving an average dialysis treatment duration of less than 3.5 hours had relative mortality risks of 1.17 to 2.18 compared with those with treatments longer than 3.5 hours ( mortality risk of 1.0 ) . Reverse causation ( the possibility that more seriously ill patients received dialysis for a shorter time ) appears unlikely . We conclude that duration of the dialysis procedure is an important element in determining patient mortality as one of the factors determining the adequacy of dialysis Output:	Hemodialysis care in private not-for-profit centers is associated with a lower risk of mortality compared with care in private for-profit centers
MS212014	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The aims of this r and omized controlled trial were to evaluate the efficacy of intra-articular Hylan G-F 20 on the pain , pinch strength , and functional status in patients with thumb base osteoarthritis ( OA ) . Sixty-six h and s of 33 female patients ( mean age , 62.6 ± 6.4 years ) with bilateral clinical and radiological thumb base OA were included into this study . H and s of the same patient were divided to Hylan G-F 20 and saline-injection groups . VAS pain 100 mm , pinch strength ( key , tripod and pulp to pulp pinch ) and functionality ( Dreiser functional index ) were assessed at baseline , at sixth and 24th weeks . Statistically significant improvements were detected in function ( p = 0.001 ) , VAS pain ( p = 0.002 ) , and pinch strength ( p = 0.004 ) at the 24th week in the Hylan G-F 20 group . However , only VAS pain scores decreased temporarily in control h and s at the 6th week ( p = 0.02 ) . Although short-term placebo analgesic effect could not be ignored , intra-articular hylan was effective on pain , pinch strength , and function at the 24th week Objective : To determine the difference in the usability of three types of thenar eminence ( TE ) orthoses . Design : Prospect i ve comparative pre-experimental study with r and omized cross-over design . Setting : Rehabilitation centre . Subjects : Ten patients with osteoarthritis of the carpometacarpal I joint confirmed by X-ray . Intervention : Three types of TE orthoses , made of either supple elastic material , elastic material with a semi-rigid thumb busk or a semi-rigid ( polyethylene ) material . Main outcome measurements : Pain at the thenar eminence , pinch force , h and function , cosmesis , comfort and function of the TE orthosis . Results : The supple elastic TE orthosis scores significantly better than the more rigid types on the subjects ‘ comfort ’ , ‘ function ’ and the Green Test , while the semi-rigid orthosis scores best on ‘ cosmesis ’ . The score on the subject ‘ pain reduction ’ shows no significant difference between the three types of TE orthoses . The scores obtained correspond with the outcome of structured interviews about the usability of the TE orthoses . Conclusion : Eight out of 10 patients prefer the permanent use of a TE orthosis . Six patients chose the supple elastic orthosis and two chose the semi-rigid orthosis The purpose of this study was to compare the effects of two 6-week splint and exercise regimens for patients with trapeziometacarpal osteoarthritis . Forty participants were enrolled in a r and omised , controlled clinical trial . The experimental group received a newly design ed thumb strap splint and an abduction exercise regimen , whereas the control group received current clinical practice consisting of a short opponens splint and a pinch exercise regimen . Outcome measures included pain ( VAS at rest in cm ) , strength ( tip pinch in kg ) , and h and function ( Sollerman Test of H and Function scored out of 80 ) , measured by a blinded assessor at Weeks 0 , 2 , and 6 . By Week 6 there was no significant difference in the extent of mean improvement between the groups in : pain , 0.5 cm ( 95 % CI -1.1 to 2.1 ) ; strength , 0.1 kg ( 95 % CI -0.8 to 0.9 ) ; or h and function , 0.7 points ( 95 % CI -3.6 to 5.0 ) . While both groups improved , neither regimen is superior to the other in patients with trapeziometacarpal osteoarthritis OBJECTIVE Prospect i ve assessment of the efficacy and tolerability of intra-articular sodium hyaluronate ( SH ; Ostenil mini ) and triamcinolone acetonide ( TA ; Volon A10 ) for treatment of osteoarthritis ( OA ) of the carpometacarpal ( CMC ) joint of the thumb in a 26-week , controlled , r and omized , on an intention to treat , masked-observer study . METHODS Patients were treated with three intra-articular injections of either SH ( n = 28 ) or TA ( n = 28 ) . Primary assessment s were pain according to a 100 mm visual analogue scale and extensive clinical and functional parameters such as swelling , grip power and range of motion . The population was analysed using one- and two-sided Mann-Whitney ( MW ) estimators . RESULTS Maximum pain relief occurred at 2 - 3 weeks for TA and at week 26 for SH after the first intra-articular injection . At weeks 2 - 3 TA was significantly better than SH ( MW : 0.3319 and 0.3063 ; P = 0.9827 and 0.9929 ) . At week 26 a slight superiority of SH could be observed ( MW : 0.53 ; P = 0.3624 ) and non-inferiority could be proven . After 26 weeks lateral pinch power was significantly better in the SH-group ( MW : 0.6331 ; P = 0.0226 ) . In all , 88.0 % of patients treated with SH and 79.1 % of the TA-group described pain improvement after 26 weeks . Both agents were well tolerated . No adverse events with causal connection to the investigational products occurred . CONCLUSION A single course of three SH injections is effective in relieving pain and improving joint function in patients with OA of the CMC joint of the thumb . Although in comparison with triamcinolone its effects are achieved more slowly , the results indicate a superior long-lasting effect of hyaluronan at 6 months after end of treatment period PURPOSE Conservative , nonsurgical therapies for basal joint osteoarthritis , such as thumb spica splinting and intra-articular corticosteroid injections , remain the mainstays for symptomatic treatment . This study compares intra-articular hylan , corticosteroid , and placebo injections with regard to pain relief , strength , symptom improvement , and metrics of manual function in a r and omized , controlled , double-blinded study . METHODS Sixty patients with basal joint arthritis were r and omized to receive 2 intra-articular hylan injections 1 week apart , 1 placebo injection followed by 1 corticosteroid injection 1 week later , or 2 placebo injections 1 week apart . Patients were evaluated at 2 , 4 , 12 , and 26 weeks and assessed with Visual Analog Scale pain scores , strength measures , difference scores , Disabilities of the Arm , Shoulder , and H and ( DASH ) scores , and range of motion measurements . RESULTS All groups reported pain relief at 2 weeks . The steroid and placebo groups had significantly less pain at week 4 compared with baseline , but this effect disappeared by week 12 . Only hylan injections continued to provide pain relief at 12 and 26 weeks compared with baseline . There were no significant differences in pain between groups at any time . At 12 and 26 weeks , the hylan group had improved grip strength compared with baseline , whereas the steroid and placebo groups were weaker . At 4 weeks , the steroid group reported in the difference score a greater improvement in symptoms ( 68 % ) compared with the hylan ( 44 % ) and placebo ( 50 % ) groups . Whereas at 26 weeks the hylan group reported the largest improvement in symptoms ( 68 % ) , this was not statistically different from the placebo ( 47 % ) and steroid ( 58 % ) groups . There were no significant differences in Disabilities of the Arm , Shoulder , and H and scores or range of motion among the groups . There were no complications from any injection . CONCLUSIONS There were no statistically significant differences among hylan , steroid , and placebo injections for most of the outcome measures at any of the follow-up time points . However , based on the durable relief of pain , improved grip strength , and the long-term improvement in symptoms compared with preinjection values , hylan injections should be considered in the management of basal joint arthritis of the thumb . TYPE OF STUDY /LEVEL OF EVIDENCE Therapeutic The purpose of this study was to compare the objective , subjective , and radiographic responses of patients with carpometacarpal joint osteoarthritis ( CMCJ-OA ) wearing a prefabricated neoprene splint ( PFN ) , which crosses the CMCJ and metacarpophalangeal joint , with those of patients wearing a custom-made thermoplastic short opponens splint ( CMT ) , which crosses only the CMCJ . Patients ( N = 25 ) with first CMCJ stage I and II osteoarthritis were assigned r and omly to wear either the PFN splint or the CMT splint for one week . After one week , the subjects rated their function in the splint and their satisfaction and pain levels on visual analogue scales . Pinch measurements were performed and x-rays were taken to assess carpometacarpal subluxation . The second splint was then applied for one week and all measures were repeated . The subjects rated the PFN splint significantly higher , and most reported that they would choose the PFN splint over the CMT splint for daily and long-term use . Both pain and function were improved with splinting , but the effect was amplified with the PFN splint compared with the CMT splint . Both splints reduced subluxation at the first carpometacarpal joint , but the CMT effect was greater . This study further supports current evidence that subjects with stage I and II first CMCJ-OA will have pain relief with thumb splinting . In addition , the PFN splint will provide greater relief when compared with the CMT splint . Furthermore , this study reveals that patients prefer the PFN splint to the CMT splint Output:	Systematic evaluation demonstrated the following : ( 1 ) H and therapy can possibly reduce pain . 2 ) Although both steroid and hyaluronate intra-articular injections can provide pain relief , most authors conclude that injection of hyaluronate is more effective . 3 ) The use of orthoses reduces pain without effect on function , strength , or dexterity . 6 ) There are no high-level evidence studies specifically evaluating the effect of analgesics and patient education in joint protection in patients with thumb base OA . Available evidence suggests only some effect of orthoses and intra-articular hyaluronate or steroid injections
MS212015	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: INTRODUCTION While cross-sectional studies have shown that hookah tobacco smoking ( HTS ) is an increasingly popular behavior among university students , little is known about factors associated with initiation . This study sought to determine associations between knowledge , attitudes , and normative beliefs and initiation of HTS among university students . METHODS Data were from a prospect i ve longitudinal cohort study of 569 r and omly selected first- and second-year university students . Online question naires that were developed in accordance with our composite theoretical model were completed in September 2010 and April 2011 . RESULTS About one-seventh ( 13 % ) of participants initiated HTS by follow-up . Positive attitudes and favorable normative beliefs were associated with increased adjusted odds of initiation ( AOR = 4.12 , 95 % CI = 2.56 , 6.59 ; and AOR = 2.01 , 95 % CI = 1.35 , 2.99 , respectively ) , while negative attitudes were associated with decreased adjusted odds ( AOR = 0.62 , 95 % CI = 0.48 , 0.80 ) . Correct knowledge regarding toxicants associated with HTS was not significantly associated with initiation . CONCLUSIONS While positive attitudes and favorable normative beliefs are associated with initiation of HTS in a cohort of never-users , increased knowledge about toxins is not associated with lower initiation . It may be particularly valuable for educational interventions to attempt to alter positive attitudes and normative beliefs related to HTS Background Although waterpipe tobacco smoking seems to be increasing on U.S. university campuses , these data have come from convenience sample s. Purpose We aim ed to determine the prevalence of and associations with waterpipe tobacco smoking among a r and om sample of students . Methods We surveyed a r and om sample of graduate and undergraduate students at a large , urban university . We used multivariate modeling to determine independent associations between belief-related predictors and waterpipe tobacco smoking . Results Of the 647 respondents , waterpipe smoking was reported in 40.5 % , over the past year in 30.6 % , and over the past 30 days in 9.5 % . Over half of the sample ( 52.1 % ) perceived that tobacco smoking from a waterpipe was less addictive than cigarette smoking . In fully adjusted multivariate models , 1-year waterpipe smoking was associated with low perceived harm ( OR = 2.54 , 95 % CI = 1.68 , 3.83 ) , low perceived addictiveness ( OR = 4.64 , 95 % CI = 3.03 , 7.10 ) , perception of high social acceptability ( OR = 20.00 , 95 % CI = 6.03 , 66.30 ) , and high perception of popularity ( OR = 4.72 , 95 % CI = 2.85 , 7.82 ) . Conclusions In this sample , lifetime waterpipe use was as common as lifetime cigarette use . Perception of harm , perception of addictiveness , social acceptability , and popularity were all strongly related to waterpipe smoking INTRODUCTION Tobacco use in low- to middle-income countries is a major public health concern for both smokers and those exposed to environmental tobacco smoke ( ETS ) . Egypt has made important strides in controlling tobacco use , but smoking and ETS remain highly prevalent . This r and omized intervention sought to improve the target population 's knowledge regarding the hazards of smoking and ETS and to change attitudes and smoking behaviors within the community and the household . METHODS In this 2005 - 2006 study in Egypt 's Qalyubia governorate , trained professionals visited schools , households , mosques , and health care centers in rural villages r and omly selected for the intervention to discuss the adverse effects of smoking and ETS exposure and ways to reduce one 's ETS exposure . Data collected in interviewer-facilitated surveys before and after the intervention period were analyzed in pairwise comparisons with data from control villages to assess the effectiveness of the intervention in achieving its aims . RESULTS The intervention group showed a greater increase in underst and ing the dangers associated with smoking cigarettes and waterpipes and became more proactive in limiting ETS exposure by asking smokers to stop , avoiding areas with ETS , and enacting smoking bans in the home . However , the intervention had little to no impact on the number of smokers and the amount of tobacco smoked . CONCLUSIONS Results are consistent with previous studies showing that changing smokers ' behavior can be difficult , but community-wide efforts to reduce ETS exposure through smoking bans , education , and empowering people to ask smokers to stop are effective . The method can be generalized to other setting INTRODUCTION Although water pipe tobacco smoking is common in Lebanon and Syria , prevalence in neighboring Jordan is uncertain . The purpose s of this study were ( a ) to assess the prevalence of water pipe tobacco smoking among university students in Jordan and ( b ) to determine associations between sociodemographic variables and water pipe tobacco smoking in this population . METHODS A trained interviewer administered a question naire among r and omly selected students at four prominent universities in Jordan . The question naire assessed sociodemographic data , personal history of water pipe tobacco use , and attitudes regarding water pipe tobacco smoking . We used logistic regression to determine independent associations between sociodemographic and attitudinal factors and each of two dependent variables : ever use of water pipe and use at least monthly . RESULTS Of the 548 participants , 51.8 % were male and mean age was 21.7 years . More than half ( 61.1 % ) had ever smoked tobacco from a water pipe , and use at least monthly was reported by 42.7 % . Multivariable analyses controlling for all relevant factors demonstrated significant associations between ever use and only two sociodemographic factors : ( a ) gender ( for women compared with men , odds ratio [ OR ] = 0.11 , 95 % CI = 0.07 - 0.17 ) and ( b ) income ( for those earning 500 - 999 Jordanian dinar ( JD ) monthly vs. < 250 JD monthly , OR = 2.37 , 95 % CI = 1.31 - 4.31 ) . There were also significant associations between perception of harm and addictiveness and each outcome . DISCUSSION Water pipe tobacco smoking is highly prevalent in Jordan . Although use is associated with male gender and upper middle income levels , use is widespread across other sociodemographic variables . Continued surveillance and educational interventions emphasizing the harm and addictiveness of water pipe tobacco smoking may be valuable in Jordan INTRODUCTION In Egypt , each faculty has it own students ' union , which represents the students and collaborates in organizing all educational , sporting and social activities . The objectives of the current study were to evaluate the knowledge of members of students ' unions about cigarette and Shisha smoking together with assessing their attitudes towards smoking in public places in general and in the university . METHODOLOGY A r and om sample of members of Ain Shams University Students ' Unions was subjected to an interview question naire . All participants were individually interviewed face-to-face by a trained interviewer from March 1 , 2005 to April 30 , 2005 . RESULTS Our study showed that 34 ( 31.5 % ) students were smokers . The mean knowledge score percentage was 79.4 + /- 20.7 . Regarding knowledge about Shisha smoking hazards , the majority of the students ( 84.3 % ) knew that Shisha smoking is hazardous . The mean attitude score percentage was 56.8 + /- 22.2 . Smokers had less mean knowledge as regard smoking hazards compared to non-smokers ( p < 0.01 ) . Also , smokers had a lower mean attitude compared to non-smokers ( p < 0.001 ) . More than one-third ( 38.9 % ) of the interviewed students did n't know if the students ' union has a policy for prevention of smoking or not . CONCLUSION Our findings point that although our students had a moderately high mean knowledge score yet this did n't increase their attitude about the smoking problem in the university and in the community . This supports the notion that , in addition to knowledge about smoking hazards , efforts are needed to change beliefs that allow this offensive habit to continue SETTING Waterpipe smoking is becoming a global health crisis among youth . OBJECTIVE To identify the prevalence of waterpipe use among Iranian university students and to explore perceived reasons for use . METHODS A r and om sample of 1024 university students at two major universities in South Iran was enrolled in the study . A three-part question naire ( baseline data , tobacco smoking status and perceived reasons for waterpipe use ) was used . Students filled out the self-administered question naire in their classrooms . RESULTS The prevalence of waterpipe smoking in the respondents ' lifetime and in the last 30 days was 42.5 % and 18.7 % , respectively . The mean age at initiation of waterpipe smoking was 16.3 ± 3.2 years . Ever smoking was positively associated with age and male sex , whereas no association was found regarding marital status . The highest odds of lifetime waterpipe smoking were observed in students with close friends who smoked the waterpipe ( 5.94 , 95%CI 4.26 - 8.30 ) . The most important perceived reason for waterpipe smoking as stated by students was enjoyment ( 55.8 % ) . CONCLUSION Given the alarming prevalence of waterpipe smoking , preventive measures should be adopted among university students taking into account the influence of peers , siblings and parents in the lessening social tolerance of waterpipe smoking Background and objectives Narghile is becoming the favorite form of tobacco use by youth globally . This problem has received more attention in recent years . The aim of this study was to investigate the prevalence and pattern of narghile use among students in three public Jordanian universities ; to assess their beliefs about narghile 's adverse health consequences ; and to evaluate their awareness of oral health and oral hygiene . Methods The study was a cross-sectional survey of university students . A self-administered , anonymous question naire was distributed r and omly to university students in three public Jordanian universities during December , 2008 . The question naire was design ed to ask specific questions that are related to smoking in general , and to narghile smoking in specific . There were also questions about oral health awareness and oral hygiene practice s. Results 36.8 % of the surveyed sample indicated they were smokers comprising 61.9 % of the male students and 10.7 % of the female students in the study sample . Cigarettes and narghile were the preferred smoking methods among male students ( 42 % ) . On the other h and , female students preferred narghile only ( 53 % ) . Parental smoking status but not their educational level was associated with the students smoking status . Smokers had also significantly poor dental attendance and poor oral hygiene habits . Conclusion This study confirmed the spreading narghile epidemic among young people in Jordan like the neighboring countries of the Eastern Mediterranean region . Alarming signs were the poor oral health awareness among students particularly smokers National data indicate nearly a quarter of college students smoked from a hookah at some point in their lifetime regardless of gender . To address this issue , research ers assessed the perceptions , knowledge , beliefs of hookah users at a large Midwestern University and also determined what other drug related high-risk behaviors were associated with this behavior . An anonymous , online survey was sent to 2,000 r and omly selected undergraduate students from a large Midwestern University . Research ers used a cross sectional research design to determine the prevalence and motivating factors associated with hookah use . Respondents included 438 individuals ( 60 % female ) with an average age of 23.1 ( SD = 12.32 ) , yielding a response rate of 22 % . Approximately 15.4 % of the sample had previously smoked hookah , while 6 % used hookah within the past 30 days . Common motivating factors associated with smoking hookah included socializing/partying ( 29 % ) , peer influence ( 27 % ) , and for relaxation ( 25 % ) . Correlations were calculated comparing hookah use to other high risk behaviors with the two highest correlations consisted of 30-day tobacco use ( r = 0.67 ) and marijuana ( r = 0.39 ) . The results from this study suggest hookah use is limited to a small percentage of students . Students appear to smoke hookah for social reasons and underestimate the addictive properties associated with the product . Research ers and practitioners need to develop and evaluate specific interventions to educate college students about the health hazards associated with hookah use Introduction Hookah smoking is becoming increasingly popular among young adults and is often perceived as less harmful than cigarette use . Prior studies show that it is common for youth and young adults to network about substance use behaviors on social media . Social media messages about hookah could influence its use among young people . We explored normalization or discouragement of hookah smoking , and other common messages about hookah on Twitter . Methods From the full stream of tweets posted on Twitter from April 12 , 2014 , to May 10 , 2014 ( approximately 14.5 billion tweets ) , all tweets containing the terms hookah , hooka , shisha , or sheesha were collected ( n = 358,523 ) . The hookah tweets from Twitter users ( tweeters ) with high influence and followers were identified ( n = 39,824 ) and a r and om sample of 5,000 tweets was taken ( 13 % of tweets with high influence and followers ) . The sample of tweets was qualitatively coded for normalization ( ie , makes hookah smoking seem common and normal or port Output:	Socio-cultural and peer influences were major contributing factors that encouraged students to initiate WTS . Furthermore , WTS dependence had two components : psychological and social . This was compounded by the general perception that WTS is a less harmful , less addictive and more sociable alternative to cigarette smoking . Knowledge of WTS harms failed to correlate with a reduced risk of WTS use , and some students reported symptoms of WTS addiction . A large proportion of students believed that quitting WTS was easy , yet few were able to do so successfully . Finally , students believed current public health campaigns to educate on WTS harms were inadequate and , particularly in the global north , were not required . Conclusion Reasons for WTS amongst university students are multi-faceted .
MS212016	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: A r and omized comparison of the usual surgical removal of nasal polyps versus systemic steroid treatment was performed in 53 patients . In all , continuous topical steroid treatment was given during the one year period of observation . In both groups the initial treatment result ed in a continuous increase in mean nasal expiratory peak flow as well as in the sense of smell ; these two parameters showed a temporary statistically significant difference in favour of the medically treated group . In general though , the results in the two treatment groups were alike . Therefore medical treatment is recommended for routine use . Surgical removal should be reserved for those few cases in which the presence of residual or recurrent polyps justifies the inherent risks and discomfort for the patient Patients with nasal polyps present repeatedly in otorhinolaryngology practice s , but the prevalence of nasal polyps in the general population is not known . Our objective was to investigate the prevalence of nasal polyps in an adult Swedish population in relation to age , gender , asthma , and aspirin intolerance . A r and om sample of 1,900 inhabitants over the age of 20 years , stratified for age and gender , was drawn from the municipal population register in Skövde , Sweden , in December 2000 . The subjects were called to clinical visits that included questions about rhinitis , asthma , and aspirin intolerance and examination by nasal endoscopy . In total , 1,387 volunteers ( 73 % of the sample ) were investigated . The sample size was adequate , with a good fit to the whole population . The prevalence of nasal polyps was 2.7 % ( 95 % confidence interval , 1.9–3.5 ) , and polyps were more frequent in men ( 2.2 to 1 ) , the elderly ( 5 % at ≥60 years of age ) , and asthmatics . Subjective symptoms of aspirin intolerance were not found to correlate with polyps . Nasal polyps were more common in adults than was stated by the a priori estimate . The Skövde population -based study is considered representative for the Swedish population OBJECTIVE To reevaluate the current criteria for diagnosing allergic fungal sinusitis ( AFS ) and determine the incidence of AFS in patients with chronic rhinosinusitis ( CRS ) . METHODS This prospect i ve study evaluated the incidence of AFS in 210 consecutive patients with CRS with or without polyposis , of whom 101 were treated surgically . Collecting and culturing fungi from nasal mucus require special h and ling , and novel methods are described . Surgical specimen h and ling emphasizes histologic examination to visualize fungi and eosinophils in the mucin . The value of allergy testing in the diagnosis of AFS is examined . RESULTS Fungal cultures of nasal secretions were positive in 202 ( 96 % ) of 210 consecutive CRS patients . Allergic mucin was found in 97 ( 96 % ) of 101 consecutive surgical cases of CRS . Allergic fungal sinusitis was diagnosed in 94 ( 93 % ) of 101 consecutive surgical cases with CRS , based on histopathologic findings and culture results . Immunoglobulin E-mediated hypersensitivity to fungal allergens was not evident in the majority of AFS patients . CONCLUSION The data presented indicate that the diagnostic criteria for AFS are present in the majority of patients with CRS with or without polyposis . Since the presence of eosinophils in the allergic mucin , and not a type I hypersensitivity , is likely the common denominator in the pathophysiology of AFS , we propose a change in terminology from AFS to eosinophilic fungal rhinosinusitis The effects of rhinosinusitis treatment upon asthma are disputed . The first r and omised prospect i ve study of surgical compared with medical therapy of chronic rhinosinusitis in 90 patients with and without nasal polyps was previously reported . Asthma symptoms , control , forced expiratory volume in one second ( FEV1 ) , peak flow , exhaled nitric oxide , medication use and hospitalisation at 6 and 12 months from the start of the study were also monitored . This paper reports these results in 43 of those patients with concomitant asthma . Both medical and surgical treatment of chronic rhinosinusitis were associated with subjective and objective improvements in asthma . Overall asthma control improved significantly following both treatment modalities , but was better maintained after medical therapy , where improvement could also be demonstrated in the subgroup with nasal polyps . Medicine was superior to surgery with respect to a decrease in exhaled nitric oxide and increase in FEV1 in the polyp patients . Two patients noted worsening of asthma post-operatively . Improvement in upper airway symptoms , as assessed using a visual analogue scale , correlated with improvement in asthma symptoms and control . Treatment of chronic rhinosinusitis , medical or surgical , benefits concomitant asthma ; that associated with nasal polyposis benefits more from medical therapy OBJECTIVES To conduct the first prospect i ve r and omized controlled trial , evaluating and comparing the effect of medical and surgical treatment of chronic rhinosinusitis ( CRS ) on quality of life . MATERIAL S AND METHODS Ninety patients with CRS , who remained symptomatic after initial medical treatment with Dexarhinaspray duo and nasal douche , were r and omized either to medical or surgical therapy . All patients underwent pre- and post-treatment assessment s of the Sinonasal Outcome Test-20 ( SNOT-20 ) , and the Short Form 36 Health Survey ( SF-36 ) . Each patient had three assessment s : before starting the r and omized treatment , after six months and finally after one year . RESULTS Both the medical and surgical treatment of CRS significantly improved almost all the parameters of SNOT and SF-36 ( p<0.05 ) , with no significant difference being found between the medical and surgical groups ( p>0.05 ) . CONCLUSION Both maximal medical and surgical therapy of CRS improves the quality of life of CRS patients , providing further evidence that chronic rhinosinusitis should be targeted with maximal medical therapy in the first instance , with surgical treatment being reserved for cases refractory to medical therapy . The presence of nasal polyps does not imply any negative effect on the quality of life after CRS therapy , either medical or surgical BACKGROUND The treatment of nasal polyps is controversial , and medical treatment alone has been little investigated to our knowledge . OBJECTIVE To examine the efficacy of therapy using only topical budesonide powder and topical budesonide powder supplemented with surgical removal or intramuscular betamethasone . DESIGN R and omized , double-blind comparison of 2 dosages and additional treatment , if therapy failed . After 1 year , treatment with medication was stopped , and the dem and for renewed treatment was monitored for another year . PATIENTS Patients with bilateral nasal polyps who dem and ed treatment were consecutively enrolled in a hospital outpatient clinic or specialty private practice . During a 15-month period from 1990 to 1992 , a total of 126 patients entered the 2-year study . INTERVENTIONS In phase 1 , r and omized and double-blind treatment with a topical medication , budesonide powder , 800 micrograms or 400 micrograms daily , or a placebo was given for 1 month . In phase 2 , r and omized and double-blind treatment with budesonide powder , 800 micrograms or 400 micrograms daily , was given . At the end of phase 1 , failed therapy was supplemented by r and omly assigned treatment of either surgical removal or a single injection of sustained released betamethasone . In phase 3 , treatment with the medication was discontinued , and patients were monitored for another year . The time when treatment was required again was noted . The present article deals with phases 2 and 3 . MAIN OUTCOME MEASURES Patients ' scores of treatment efficacy as well as symptoms and signs . Semiquantitative measurement of sense of smell and calculation of peak expiratory flow rate index based on nasal and oral peak expiratory flow . RESULTS In all outcome measures , a comparison of the data before treatment with the corresponding figures during phase 2 showed statistically significant efficacy . The clinical course was described at the end of phase 2 . About 85 % of the patients , including those who received additional therapy because the initial therapy failed , rated total or substantial control over the symptoms . The 2 dosages investigated showed equal results . These findings were consistent with the signs recorded and the peak expiratory flow rate index . The results of phase 3 showed that 50 % of patients had dem and ed treatment after 4 months , while 34 % managed without medication after 1 year . CONCLUSIONS The clinical course in this study showed that most patients with nasal polyps do well with medical treatment . Therefore , surgery was required in few patients . However , the potential of medical treatment should be further explored in future studies BACKGROUND Nasal polyposis ( NP ) is a frequent inflammatory chronic disease of the upper respiratory tract , which may impair quality of life ( QOL ) . The NP impact , which is frequently associated with lower respiratory disorders , has never before been studied . OBJECTIVE We initiated this prospect i ve study to establish internal validity and reliability of the generic SF-36 question naire in NP and to determine to what level daily functioning becomes impaired as a result of NP . METHODS Forty-nine consecutive patients with NP were included . They were assessed for the severity of nasal symptoms and underwent pulmonary function tests . The QOL profiles in patients with NP were compared with those of patients with perennial rhinitis ( n = 111 ) and healthy subjects ( n = 116 ) . RESULTS Cronbach 's coefficient alpha demonstrated the high reliability and validity of the SF-36 question naire for patients with NP ( alpha = .89 ) . NP impaired QOL more than perennial allergic rhinitis ( P < .05 ) . The impairment of QOL was greater when NP was associated with asthma ( P < .05 ) . SF-36 scores appeared highly correlated to pulmonary function ( FEV1 , maximal midexpiratory flow , forced vital capacity ) , suggesting relationships between QOL in NP and associated bronchial obstruction . Severity of nasal symptoms were not related to QOL scales . In addition , sequential evaluations of QOL , nasal symptoms , and pulmonary function were performed 10 months after the first evaluation in 28 patients with NP . These evaluations demonstrated that NP treatment either with nasal steroids or endonasal ethmoidectomy significantly improved both nasal symptoms and QOL without significant change of pulmonary function . CONCLUSION Our study clearly demonstrated that the SF-36 question naire presented a high internal validity and reliability in patients with NP . NP impaired QOL to a greater degree than perennial allergic rhinitis . QOL improvement after NP treatment is related to nasal symptoms improvement OBJECTIVES /HYPOTHESIS Genetic etiology is suspected in the development of nasal polyposis on the basis of familial aggregation . This study investigated whether there is an association between HLA-DRB1 , -DQA1 , and -DQB1 alleles and developing nasal polyposis . STUDY DESIGN Data from 50 polypectomized patients were compared with data from 50 healthy r and omly selected controls . Polyp score , possible asthma , aspirin sensitivity , and ASA triad were also recorded . METHODS Genotyping of HLA-DRB1 alleles was carried out with the Dynal RELI SSO HLA-DRB , a direct DNA probe test that utilizes a polymerase chain reaction ( PCR ) and nucleic acid hybridization for the differentiation of 70 HLA-DRB alleles and 9 supertypes . For DQA1 * genotyping PCR-RFLP ( restriction fragment length polymorphism ) was used , differentiating eight alleles . The DQB1 * typing was carried out using a INNO-LiPA DQB PCR-reverse hybridization kit , allowing the discrimination of 30 alleles . RESULTS People carrying the HLA-DR7-DQA1 * 0201 , and -DQB1 * 0202 haplotype were found to have a two to three times higher odds ratios ( ORs ) for developing the disease , compared with controls . Patients with ASA triad carried the above-mentioned DR7 allele with the linked alleles significantly more often ( P < .001 ) . Subjects carrying HLA-DR5 allele and the linked alleles had lower odds ratio values . CONCLUSION These results underline that allergy is not conditional for the formation of nasal polyps as thought before . Nasal polyposis associated with asthma and aspirin sensitivity is probably a unique form of nasal polyps . The authors plan further investigations in this field Our underst and ing of fungi in chronic rhinosinusitis ( CRS ) has been limited by previously employed detection techniques . This study examines the fungal component of the microbiome in CRS patients and controls using a highly sensitive culture‐independent molecular technique . The aims of this study include the characterization of fungal richness , prevalence , abundance , temporal changes , and their relationship with patient outcomes OBJECTIVES To conduct the first prospect i ve , r and omized , controlled trial evaluating and comparing the medical and surgical treatment of polypoid and nonpolypoid chronic rhinosinusitis ( CRS ) . MATERIAL S AND METHODS Ninety patients with CRS were equally r and omized either to medical or surgical therapy . All patients underwent pre- and posttreatment assessment s of visual analogue score ( VAS ) , the Sinonasal Outcome Test-20 ( SNOT-20 ) , the Short Form 36 Health Survey ( SF-36 ) , nitric oxide ( NO ) , acoustic rhinometry , saccharine clearance time ( SCT ) , and nasal endoscopy . Each patient had three assessment s : before starting the treatment , after 6 months , and Output:	PRIMARY OUTCOMES symptom scores and quality of life scores There were no important differences between groups in either the patient-reported disease-specific symptom scores or the health-related quality of life scores . No differences were found for any objective measurements or olfactory tests in those studies in which they were measured . The evidence does not show that one treatment is better than another in terms of patient-reported symptom scores and quality of life measurements .
MS212017	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: PURPOSE To evaluate the efficacy and toxicity of accelerated radiotherapy in patients with primary high grade glioma , where acceleration is used as a means of delivering a shortened course of radical radiotherapy . PATIENTS AND METHODS Two-hundred and eleven patients with primary high grade glioma were treated at the Royal Marsden NHS Trust between 1987 and 1997 with accelerated radiotherapy ( 55 Gy in 34 fractions twice daily ) , to planning target volume ( PTV ) defined as enhancing tumour and a 3 cm margin . All had histologically confirmed high grade glioma ( 53 anaplastic astrocytoma , 137 glioblastoma multiforme , 4 gliosarcoma , 5 gemistocytic astrocytoma , 12 high grade astrocytoma not otherwise specified ) . The mean Karnofsky performance status ( KPS ) was 90 and median age was 54 years ( range 19 - 77 ) . RESULTS Of 211 patients entered , 201 were able to complete radiotherapy ; 39 patients ( 19 % ) had deterioration in KPS during radiotherapy and this was transient in 11 . Median survival of 211 patients was 10 months with 1 year , 2 year , and 3 year survival probabilities of 38 % , 14 % , and 8 % respectively . Age and extent of excision were independent prognostic factors for survival . Previous comparison to matched cohort receiving 60 Gy in 30 daily fractions did not demonstrate significant survival difference . CONCLUSION Accelerated radiotherapy is a feasible treatment approach for patients with high grade glioma . The survival and functional outcome are comparable to conventional radiotherapy and the treatment is without serious acute toxicity . While acceleration of conventional dose irradiation could be tested in r and omised studies , it is unlikely this approach would result in a clinical ly meaningful survival benefit . Accelerated radiotherapy therefore remains one of the ways of delivering radical irradiation in patients with high grade glioma . However , it adds complexity to what is a palliative treatment regimen and the rationale and advisability should be re-examined , particularly in terms of impact on quality of life , true patient preference , and health economic considerations BACKGROUND It is controversial if distant recurrence of glioblastoma is more common after temozolomide ( TMZ ) concurrent with radiotherapy ( RT ) . Optimal therapy for patients with recurrent disease after RT/TMZ is unclear . Our purpose was to evaluate recurrence patterns in glioblastoma and the effect of treatment at recurrence upon survival . METHODS We performed a retrospective review of 67 patients with newly diagnosed glioblastoma treated with RT/TMZ between 2003 - 2007 . Statistical analyses included Kaplan-Meier method for survival , and multivariate Cox proportional hazards model for the effect of salvage treatment on survival . RESULTS 58 patients ( 86.6 % ) recurred locally ; 9 patients ( 13.4 % ) had a distant non-contiguous focus of new disease . Median survival(MS ) was 17 months ; median time-to-progression(TTP ) 6.8 months . The local and distant groups had comparable prognostic factors . There was no difference in MS(p=0.35 ) or TTP(p=0.95 ) by location of recurrence . At relapse , 26 patients ( 38.8 % ) received continuous , dose-intense TMZ , 24(35.8 % ) other therapy(4.5 % RT ; 20.9 % lomustine+/-procarbazine ; 4.5 % etoposide ; 1.5 % conventional TMZ ; 4.5 % TMZ then lomustine ) , and 17(25.4 % ) were untreated . Dose-intense TMZ was associated with prolonged MS compared to all other patients ( 21.5 months vs. 12.4 months , p=0.019 , HR=3.86 , 95%CI : 1.81 - 8.22 ) and similar to MS with other chemotherapy regimens(18.8 months , p=0.40 , HR=1.30 , 95 % CI : 0.65 - 2.61 ) . CONCLUSION The pattern of recurrence of glioblastoma treated with RT/TMZ was predominantly local . Second-line treatment with continuous dose-intense TMZ may prolong survival in patients with recurrent glioblastoma . Overall survival is similar to other conventional salvage regimens ; however TMZ may be better tolerated . This study is limited by its retrospective nature and potential selection bias . Prospect i ve controlled studies are needed PURPOSE In patients with newly diagnosed glioblastoma multiforme , to determine whether cisplatin plus carmustine ( BCNU ) administered before and concurrently with radiation therapy ( RT ) improves survival compared with BCNU and RT and whether survival using accelerated RT ( ART ) is equivalent to survival using st and ard RT ( SRT ) . PATIENTS AND METHODS After surgery , patients were stratified by age , performance score , extent of surgical resection , and histology ( glioblastoma v gliosarcoma ) and then r and omly assigned to arm A ( BCNU plus SRT ) , arm B ( BCNU plus ART ) , arm C ( cisplatin plus BCNU plus SRT ) , or arm D ( cisplatin plus BCNU plus ART ) . RESULTS Four hundred fifty-one patients were r and omly assigned , and 401 were eligible . Frequent toxicities included myelosuppression , vomiting , sensory neuropathy , and ototoxicity and were worse with cisplatin . There was no difference in toxicity between SRT and ART . Median survival times and 2-year survival rates for patients who received BCNU plus RT ( arms A and B ) compared with cisplatin , BCNU , and RT ( arms C and D ) were 10.1 v 11.5 months , respectively , and 11.5 % v 13.7 % , respectively ( P = .19 ) . Median survival times and 2-year survival rates for patients who received SRT ( arms A and C ) compared with ART ( arms B and D ) were 11.2 v 10.5 months , respectively , and 13.8 % v 11.4 % , respectively ( P = .33 ) . CONCLUSION Cisplatin administered concurrently with BCNU and RT result ed in more toxicity but provided no significant improvement in survival . SRT and ART produced similar toxicity and survival In Brain Tumor Cooperative Group Study 77 - 02 , eleven institutions r and omized 603 adult patients with supratentorial malignant glioma to one of four treatment groups following surgery : conventional radiotherapy ( 6000 cGy in 30 - 35 fractions ) + BCNU , conventional radiotherapy + streptozotocin , hyperfractionated ( twice daily ) radiotherapy ( 6600 cGy in 60 fractions ) + BCNU , and conventional radiotherapy with misonidazole followed by BCNU . Data were analyzed for the total r and omized population and for the 557 patients ( 86 % with glioblastoma multiforme ) who met protocol eligibility specifications ( including confirmed histopathology on central review ) . Median survival was approximately 10 months following r and omization . Overall there was no statistically significant difference in survival among the four groups . Among non-glioblastoma patients , the misonidazole group appeared to have poor survival . Peripheral neuropathy was a dose-limiting toxicity with misonidazole . It is concluded that neither the addition of misonidazole nor hyperfractionated radiotherapy as given in this protocol offered any advantage over conventional radiotherapy plus either BCNU or streptozotocin for treatment of malignant glioma A total of 474 adult patients with malignant glioma ( astrocytoma ) grade 3 or 4 were r and omised into an MRC study ( BR2 ) comparing 45 Gy ( in 20 fractions over 4 weeks ) with 60 Gy ( in 30 fractions over 6 weeks ) of radiotherapy given post-operatively . Using 2:1 r and omisation , 318 patients were allocated the 60 Gy course and 156 the 45 Gy course . Adjuvant chemotherapy was not given . The results show that a 60 Gy course produces a modest lengthening of progression-free and overall survival . They suggest a statistically significant prolongation of median survival from 9 months in the 45 Gy group to 12 months in the 60 Gy group ( hazard ratio = 0.75 , chi 2 = 7.36 , d.f . = 1 , P = 0.007 ) . Over 80 % of patients reported no morbidity from the radiotherapy , and there was no evidence of increased short-term morbidity in the higher dose group . Late morbidity was not assessed . A prognostic index defined in a previous MRC study was vali date d in this new cohort . It identifies a group of patients ( 20 % of the total ) with a 2 year survival rate of 28 % ( 95 % confidence interval 19 % to 38 % ) . It was apparent that the survival advantage to the higher dose was maintained even in the poorest prognostic groups defined by this index A controlled , prospect i ve , r and omized study evaluated the use of 1,3-bis(2-chloroethyl)-1-nitrosourea ( BCNU ) and /or radiotherapy in the treatment of patients who were operated on and had histological confirmation of anaplastic glioma . A total of 303 patients were r and omized into this study , of whom 222 ( 73 % ) were within the Valid Study Group ( VSG ) , having met the protocol criteria of neuropathology , corticosteroid control , and therapeutic approach . Patients were divided into four r and om groups , and received BCNU ( 80 mg/sq m/day on 3 successive days every 6 to 8 weeks ) , and /or radiotherapy ( 5000 to 6000 rads to the whole brain through bilateral opposing ports ) , or best conventional care but no chemotherapy or radiotherapy . Analysis was performed on all patients who received any amount of therapy ( VSG ) and on the Adequately Treated Group ( ATG ) , who had received 5000 or more rads radiotherapy , two or more courses of chemotherapy , and had a minimum survival of 8 or more weeks ( the interval that would have been required to have received either the radiotherapy or chemotherapy ) . Median survival of patients in the VSG was , best conventional care : 14 weeks ( ATG : 17.0 weeks ) ; BCNU : 18.5 weeks ( ATG : 25.0 weeks ) ; radiotherapy : 35 weeks ( ATG : 37.5 weeks ) ; and BCNU plus radiotherapy : 34.5 weeks ( ATG : 40.5 weeks ) . All therapeutic modalities showed some statistical superiority compared to best conventional care . There was no significant difference between the four groups in relation to age distribution , sex , location of tumor , diagnosis , tumor characteristics , signs or symptoms , or the amount of corticosteroid used . An analysis of prognostic factors indicates that the initial performance status ( Karnofsky rating ) , age , the use of only a surgical biopsy , parietal location , the presence of seizures , or the involvement of cranial nerves II , III , IV , and VI are all of significance . Toxicity included acceptable , reversible thrombocytopenia and leukopenia A prospect i ve r and omized study of 108 patients with cerebral malignant gliomas was carried out at the Department of Radiation Oncology of Maria Sklodowska-Curie Memorial Center in Kraków . 44 patients with histologically proven glioblastoma multiforme and 64 patients with anaplastic astrocytoma received postoperative radiotherapy . Patients were r and omized to two treatment arms : Conventionally Fractionated Radiotherapy ( CFR ) and Hypofractionated Radiotherapy ( HF ) . In the CFR group , the whole brain was irradiated to the total dose of 50 Gy in 25 fractions over 5 weeks , then a 10 Gy ‘ boost ’ in 5 fractions in 5 days was delivered to the site of the primary lesion . In the HF group , there were 3 courses of irradiation separated by a one month interval . In each of the two first series the patients received 20 Gy in 5 fractions in 5 days to the whole brain , and in the third course , 10 Gy ‘ boost ’ in 5 days was delivered as in the CFR regimen . The tolerance to treatment has been found to be good in both groups . The 2-year actuarial survival rate for patients with anaplastic astrocytoma was 22 % for CFR and 18 % for HF . Patients with glioblastoma multiforme treated with HF had a better prognosis in comparison to the CFR group with the two-year actuarial survival rates being 23 % and 10 % , respectively . This difference is statistically significant at the 0.05 level Summary Purpose : To assess the effect of cisplatin ( CDDP ) plus concurrent radiation therapy on hearing loss . Methods : 451 patients with glioblastoma multiforme ( GBM ) were r and omly assigned after surgery to : Arm A : Carmustine ( BCNU ) + st and ard radiation therapy ( SRT ) ; Arm B : BCNU + accelerated radiation therapy ( ART : 160 cGy twice daily for 15 days ) ; Arm C : CDDP + BCNU + SRT ; or Arm D : CDDP + BCNU + ART . Patients on arms C and D received audiograms at baseline , and prior to the start of Output:	Although these trials may not have completely reported adverse effects , they did not note any significant toxicity attributable to radiation . Attrition , performance , detection and reporting bias for the outcome of overall survival was low . There was unclear attrition , performance , detection and reporting bias relating to the outcomes of adverse effects , progression free survival and quality of life . AUTHORS ' CONCLUSIONS Postoperative conventional daily radiotherapy improves survival for adults with good performance status and HGG as compared to no postoperative radiotherapy . Hypofractionated radiation therapy has similar efficacy for survival as compared to conventional radiotherapy , particularly for individuals aged 60 and older with glioblastoma . There is insufficient data regarding hyperfractionation versus conventionally fractionated radiation ( without chemotherapy ) and for accelerated radiation versus conventionally fractionated radiation ( without chemotherapy).There are HGG subsets who have poor prognosis even with treatment ( e.g. glioblastoma histology , older age and poor performance status ) . No r and omised trial has compared comfort measures or best supportive care with an active intervention using radiotherapy or chemotherapy in these poor prognosis patients
MS212018	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: We design ed a new treatment protocol incorporating concurrent administration of L-asparaginase ( to reduce the probability of systemic progression during concurrent chemoradiotherapy ( CCRT ) ) plus high-dose methotrexate to consolidation chemotherapy to intensify the regimen for treating localized extranodal NK/T cell lymphoma , nasal type ( ENKTL ) . CCRT comprised radiation ( 36–44 Gy ) with weekly cisplatin ( 30 mg/m2 ) and tri-weekly L-asparaginase ( 4 000 IU ) . Chemotherapy — MIDLE ( methotrexate 3 g/m2 on day 1 , etoposide 100 mg/m2 and Ifosfamide 1 000 mg/m2 on days 2–3 , dexamethasone 40 mg on days 1–4 , and L-asparaginase 6 000 IU/m2 on days 4 , 6 , 8 , 10)—was repeated every 28 days for two cycles . One of the 28 patients developed distant lesions after CCRT . The final complete response rate was 82.1 % . Four patients dropped out during or after their first MIDLE cycle due to toxicities ( recurrent G3 hyperbilirubinemia [ n = 1 ] , G3 - 5 increased creatinine [ n = 2 ] , and G5 infection [ n = 1 ] ) . With a median follow-up of 46 months ( 95 % CI : 39–47 months ) , the estimated 3-year progression-free survival rate and overall survival rate were 74.1 % and 81.5 % , respectively . This MIDLE protocol may be effective for localized ENKTL . However , concurrent administration of L-asparaginase during CCRT does not seem to provide additional benefits Extranodal natural killer/T‐cell lymphoma ( ENKTL ) , nasal‐type , is a distinct entity of lymphoid tissue . ENKTL is sensitive to radiotherapy ( RT ) , but the prognosis is poorer than for other types of early lymphoma . The treatment schedule is controversial The optimal treatment strategy for elderly patients with natural killer/T-cell lymphoma ( NKTCL ) remains to be established . A total of 63 elderly patients with newly diagnosed NKTCL were retrospectively review ed . Among the patients with stage I – II disease , 58.3 % received radiotherapy ( RT ) ± chemotherapy , and 41.7 % received chemotherapy alone . Compared with chemotherapy alone , RT ± chemotherapy elicited a significantly higher overall response rate ( ORR ) ( 100 vs. 57.1 % , P < 0.001 ) and substantially prolonged 5-year overall survival ( OS ) ( 55.3 vs. 18.0 % , P < 0.001 ) in patients with stage I – II disease . Compared with other chemotherapeutic regimens , pegaspargase plus gemcitabine and oxaliplatin (PGEMOX)/L-asparaginase plus gemcitabine and oxaliplatin ( GELOX ) was associated with a significantly higher ORR ( 92.9 vs. 51.6 % , P = 0.009 ) and a significantly improved 5-year OS ( 78.6 vs. 23.9 % , P = 0.010 ) in patients with stage I – II disease . Nine patients with stage I – II disease who were treated with PGEMOX/GELOX followed by RT had an encouraging outcome ( 5-year OS 100 % , 5-year progression-free survival ( PFS ) 85.7 % ) , which was superior to that of patients receiving other regimens followed by RT . In conclusion , RT played an important role for elderly patients with early-stage NKTCL , and the PGEMOX/GELOX regimen was superior to other regimens . The combination of them may be a promising treatment option The aim of this study was to investigate the impact of the induction treatment with SMILE ( dexamethasone , methotrexate , ifosfamide , l-asparaginase , and etoposide ) chemotherapy and consolidation with upfront autologous stem cell transplantation ( ASCT ) on clinical outcomes of patients with stage IV extranodal natural killer/T-cell lymphoma ( ENKTL ) . We analyzed the treatment response to SMILE and toxicity , and explored the feasibility of upfront ASCT in 27 patients with stage IV ENKTL out of patients who were enrolled into our prospect i ve cohort studies . The median age of patients was 45 years ( range : 17–65 years ) , and all patients had disseminated disease . The overall response rate to SMILE induction treatment was 59 % ( 16/27 ) including nine complete responses . However , five patients died due to grade IV febrile neutropenia during SMILE and six patients did not respond to SMILE . Eleven patients could undergo ASCT , and there was no transplantation-related mortality . The survival outcome of patients underwent ASCT was better than patients who could not ( P < 0.05 ) . However , four patients relapsed even after ASCT , thus , the median overall survival was 10.6 months , and the median progression-free survival was 5.1 months . Pretreatment Epstein – Barr virus ( EBV ) DNA titer was only independent prognostic factor for overall survival . In conclusion , our results suggest SMILE followed by ASCT might be an effective treatment strategy for stage IV ENKTL . However , considering frequent occurrences of disease relapse and treatment-related mortality , additional efforts are required to improve treatment outcomes of stage IV ENKTL patients PURPOSE To explore a more effective treatment for newly diagnosed stage IV , relapsed , or refractory extranodal natural killer/T-cell lymphoma , nasal type ( ENKL ) , we conducted a phase II study of the steroid ( dexamethasone ) , methotrexate , ifosfamide , L-asparaginase , and etoposide ( SMILE ) regimen . PATIENTS AND METHODS Patients with newly diagnosed stage IV , relapsed , or refractory disease and a performance status of 0 to 2 were eligible . Two cycles of SMILE chemotherapy were administered as the protocol treatment . The primary end point was the overall response rate ( ORR ) after the protocol treatment . RESULTS A total of 38 eligible patients were enrolled . The median age was 47 years ( range , 16 to 67 years ) , and the male : female ratio was 21:17 . The disease status was newly diagnosed stage IV in 20 patients , first relapse in 14 patients , and primary refractory in four patients . The eligibility was revised to include lymphocyte counts of 500/μL or more because the first two patients died from infections . No treatment-related deaths were observed after the revision . The ORR and complete response rate after two cycles of SMILE chemotherapy were 79 % ( 90 % CI , 65 % to 89 % ) and 45 % , respectively . In the 28 patients who completed the protocol treatment , 19 underwent hematopoietic stem-cell transplantation . The 1-year overall survival rate was 55 % ( 95 % CI , 38 % to 69 % ) . Grade 4 neutropenia was observed in 92 % of the patients . The most common grade 3 or 4 nonhematologic complication was infection ( 61 % ) . CONCLUSION SMILE chemotherapy is an effective treatment for newly diagnosed stage IV , relapsed or refractory ENKL . Myelosuppression and infection during the treatment should be carefully managed Circulating Epstein-Barr virus ( EBV ) DNA is a biomarker of EBV-associated malignancies . Its prognostic value in early stage NK/T-cell lymphoma ( NKTCL ) in the era of asparaginase was investigated . 68 patients were treated with a median of 4 cycles of asparaginase-based chemotherapy followed by a median of 54.6Gy ( range 50–60Gy ) radiation . The amount of EBV-DNA was prospect ively measured in both pretreatment and post-treatment plasma sample s by real-time quantitative PCR . At the end of treatment , complete response ( CR ) rate was 79.4 % , and overall response rate ( ORR ) was 88.2 % . Patients with negative pretreatment EBV-DNA had a higher CR rate ( 96.0 % vs. 69.8 % , p = 0.023 ) . The 3-year progression-free survival ( PFS ) rate and overall survival ( OS ) rate was 71 % and 83 % , respectively . In multivariate survival analysis , post-treatment EBV-DNA positivity and treatment response ( non-CR ) were prognostic factors for both worse PFS and OS ( p < 0.05 ) . Local tumor invasion was also a prognostic factor for worse OS ( p = 0.010 ) . In patients with CR , post-treatment EBV-DNA positivity correlated with inferior PFS and OS ( both p < 0.0001 ) . In patients with positive pretreatment EBV-DNA , negative post-treatment EBV-DNA correlated with better PFS and OS ( both p < 0.0001 ) . These findings indicate that post-treatment EBV-DNA positivity can predict early relapse and poor prognosis for patients with early stage NKTCL in the era of asparaginase , and may be used as an indicator of minimal residual disease We conducted a phase II trial of concurrent chemoradiotherapy ( CCRT ) followed by 2 cycles of l-asparaginase-containing chemotherapy for patients who were newly diagnosed with stages IE and IIE nasal extranodal NK/T cell lymphoma ( ENKTL ) . CCRT consisted of 40–44 Gy of radiotherapy with weekly administration of 30 mg/m2 of cisplatin for 4 weeks . Two cycles of VIDL ( etoposide ( 100 mg/m2 ) , ifosfamide ( 1,200 mg/m2 ) , and dexamethasone ( 40 mg ) from days 1 to 3 , and l-asparaginase ( 4,000 IU/m2 ) every other day from days 8 to 20 ) were administered sequentially . CCRT yielded a 90 % overall response rate without significant side effects in 30 patients , including 20 patients with complete response ( CR ) ; however , two patients showed distant disease progression . After CCRT , VIDL chemotherapy showed an 87 % final CR rate ( 26/30 ) . Although grade III or IV hematologic toxicity was frequent during VIDL chemotherapy , no treatment-related mortality was observed , and l-asparaginase-associated toxicity was manageable . With a median follow-up of 44 months , 11 patients showed local ( n = 4 ) and distant ( n = 7 ) relapse or progression . The estimated 5-year progression-free and overall survival rates were 73 and 60 % , respectively . In conclusion , CCRT followed by l-asparaginase-containing chemotherapy is a feasible treatment for newly diagnosed stages IE/IIE nasal ENKTL Purpose To explore the efficacy and safety of L-asparaginase in newly-diagnosed extranodal nature killer (NK)/T –cell lymphoma ( ENKTL ) , we conducted a prospect i ve phase II study of L-asparaginase , cyclophosphamide , vincristine , doxorubicin and dexamethasone ( CHOP-L ) regimen in combination with radiotherapy . Patients and methods Patients with newly diagnosed ENKTL and an ECOG performance status of 0 to 2 were eligible for enrollment . Treatment included 6–8 cycles of CHOP-L ( cyclophosphamide , 750 mg/m2 day 1 ; vincristine , 1.4 mg/m2 day 1 ( maximal dose 2 mg ) , doxorubicin 50 mg/m2 day 1 ; dexamethasone 10 mg days 1–8 ; L-asparaginase 6000 u/m2 days 2–8 ) . Radiotherapy was scheduled after 4–6 cycles of CHOP-L regimen , depending on stage and primary anatomic site . The primary endpoint was complete response ( CR ) rate . Results A total of 38 eligible patients were enrolled . The median age was 40.5 years ( range , 15 to 71 years ) . Their clinical characteristics were male to female ratio , 24:14 ; Ann Arbor stage I , 20 ; II , 11 ; III , 3 ; IV , 4 . CR and overall response rates were 81.6 % ( 95 % CI , 69.3 % to 93.9 % ) and 84.2 % , respectively . With a median follow-up of 25 months , the 2-year overall survival , progression-free survival and disease-free survival rates were 80.1 % ( 95%CI , 73.3 % to 86.9 % ) , 81 % ( 95%CI , 74.5 % to 87.5 % ) and 93.6 % ( 95%CI , 89.3 % to 97.9 % ) , respectively . The major adverse events were myelosuppression , liver dysfunction , and digestive tract toxicities . Grade 3 to 4 leukopenia and neutropenia were 76.3 % and 84.2 % , respectively . No treatment-related death was observed . Conclusion CHOP-L chemotherapy in combination Output:	CONCLUSIONS ASP-based CT significantly improved ORR and CR in patients with newly diagnosed both early-stage and advanced-stage ENKTL
MS212019	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND 5-Aminolevulinic acid is a non-fluorescent prodrug that leads to intracellular accumulation of fluorescent porphyrins in malignant gliomas-a finding that is under investigation for intraoperative identification and resection of these tumours . We aim ed to assess the effect of fluorescence-guided resection with 5-aminolevulinic acid on surgical radicality , progression-free survival , overall survival , and morbidity . METHODS 322 patients aged 23 - 73 years with suspected malignant glioma amenable to complete resection of contrast-enhancing tumour were r and omly assigned to 20 mg/kg bodyweight 5-aminolevulinic acid for fluorescence-guided resection ( n=161 ) or to conventional microsurgery with white light ( n=161 ) . The primary endpoints were the number of patients without contrast-enhancing tumour on early MRI ( ie , that obtained within 72 h after surgery ) and 6-month progression-free survival as assessed by MRI . Secondary endpoints were volume of residual tumour on postoperative MRI , overall survival , neurological deficit , and toxic effects . We report the results of an interim analysis with 270 patients in the full- analysis population ( 139 assigned 5-aminolevulinic acid , 131 assigned white light ) , which excluded patients with ineligible histological and radiological findings as assessed by central review ers who were masked as to treatment allocation ; the interim analysis result ed in termination of the study as defined by the protocol . Primary and secondary endpoints were analysed by intention to treat in the full- analysis population . The study is registered at http://www . clinical trials.gov as NCT00241670 . FINDINGS Median follow-up was 35.4 months ( 95 % CI 1.0 - 56.7 ) . Contrast-enhancing tumour was resected completely in 90 ( 65 % ) of 139 patients assigned 5-aminolevulinic acid compared with 47 ( 36 % ) of 131 assigned white light ( difference between groups 29 % [ 95 % CI 17 - 40 ] , p<0.0001 ) . Patients allocated 5-aminolevulinic acid had higher 6-month progression free survival than did those allocated white light ( 41.0 % [ 32.8 - 49.2 ] vs 21.1 % [ 14.0 - 28.2 ] ; difference between groups 19.9 % [ 9.1 - 30.7 ] , p=0.0003 , Z test ) . Groups did not differ in the frequency of severe adverse events or adverse events in any organ system class reported within 7 days after surgery . INTERPRETATION Tumour fluorescence derived from 5-aminolevulinic acid enables more complete resections of contrast-enhancing tumour , leading to improved progression-free survival in patients with malignant glioma Efforts to improve local control and survival by increasing the dose of once‐daily radiation therapy beyond 70 Gray ( Gy ) for patients with malignant gliomas have as yet been unsuccessful . Hyperfractionated radiation therapy ( HF ) should allow for delivery of a higher total dose without increasing normal tissue late effects , whereas accelerated hyperfractionated radiation therapy ( AHF ) may minimize tumor re population by shortening overall treatment time . The Radiation Therapy Oncology Group ( RTOG ) conducted a r and omized Phase I/II study of escalating doses of HF and AHF with carmustine ( bis‐chloroethyl nitrosourea [ BCNU ] ) for adults with supratentorial glioblastoma multiforme ( GBM ) or anaplastic astrocytoma ( AA ) . Primary study endpoints were overall survival and acute and chronic treatment‐related toxicity PURPOSE Alternative dosing schedules of temozolomide may improve survival in patients with newly diagnosed glioblastoma ( GBM ) by increasing the therapeutic index , overcoming common mechanisms of temozolomide resistance , or both . The goal of this r and omized phase II study was to evaluate two different temozolomide regimens in the adjuvant treatment of newly diagnosed GBM . PATIENTS AND METHODS Adult patients with newly diagnosed GBM were r and omly assigned to receive st and ard radiotherapy with concurrent daily temozolomide followed by six adjuvant cycles of either dose-dense ( 150 mg/m(2 ) days 1 to 7 and 15 to 21 ) or metronomic ( 50 mg/m(2 ) continuous daily ) temozolomide . Maintenance doses of 13-cis-retinoic acid were then administered until tumor progression . The primary end point was overall survival ( OS ) at 1 year . Tumor tissue was assayed to determine O(6)-methylguanine-DNA methyltransferase ( MGMT ) promoter methylation status . RESULTS Eighty-five eligible patients were enrolled ; 42 were r and omly assigned to dose-dense and 43 to metronomic temozolomide . The 1-year survival rate was 80 % for the dose-dense arm and 69 % for the metronomic arm ; median OS was 17.1 months ( 95 % CI , 14.0 to 28.1 months ) and 15.1 months ( 95 % CI , 12.3 to 18.9 months ) , respectively . The most common toxicities were myelosuppression ( leukopenia , neutropenia , and thrombocytopenia ) and elevated liver enzymes . Pseudoprogression was observed in 37 % of assessable patients and may have had an impact on estimates of progression-free survival ( 6.6 months in the dose-dense arm and 5.0 months in the metronomic arm ) . CONCLUSION Both dose-dense and metronomic temozolomide regimens were well tolerated with modest toxicity . The dose-dense regimen appears promising , with 1-year survival of 80 % One hundred and three patients with hemispheric supratentorial glioblastoma multiforme were studied . All patients were operated on and a histologic diagnosis of glioblastoma multiforme was made . Patients were r and omly placed in one of three treatment schedules within 3 weeks of surgery : Group A : combined radiation therapy and drug ( CCNU ) therapy ( 26 cases ) ; Group B : CCNU given orally every 6–8 weeks ( 27 cases ) ; Group C : st and ard radiation therapy alone ( 50 cases ) . All patients were periodically controlled by clinical and instrumental ( EEG , scan , EMG , CAT ) evaluations ; laboratory data examinations were also frequently performed . The treatment results have been evaluated according to length of survival , social quality of life , and positive or negative response to chemotherapy . In our opinion the clinical findings are interesting but the statistical results are somewhat negative , especially when the groups of patients are not homogeneous A prospect i ve r and omized controlled multicenter phase III trial was conducted to evaluate the effects of neoadjuvant chemotherapy with nimustine (ACNU)-cisplatin ( CDDP ) when used in conjunction with radiotherapy plus adjuvant temozolomide in patients with newly diagnosed glioblastoma . The study population was r and omly assigned into one treatment and one control group . Both groups received radiotherapy followed by six cycles of adjuvant oral temozolomide ( 150–200 mg/m2 ) for 5 days every 28 days after surgery . Prior to radiotherapy , the treatment group also received two cycles , 6 weeks apart , of neoadjuvant chemotherapy with ACNU ( 40 mg/m2/day ) and CDDP ( 40 mg/m2/day ) infused continuously for 72 h. The primary end-point was median survival time . The study has closed after interim analysis with a total of 82 patients ( 48.8 % of target number ) due to unacceptable high frequency of toxicity profiles in spite of the promising actuarial survival outcome . Median survival time was 28.4 months [ 90 % confidence interval ( CI ) , 21.1 months to not available ] in the treatment group and 18.9 months ( 90 % CI , 17.1–27.4 months ) in the control group ( P = 0.2 ) . The 2-year survival rate and progression-free survival time were 50.9 % and 6.6 months ( 90 % CI , 3.5–9.5 months ) in the treatment group and 27.8 % and 5.1 months ( 90 % CI , 3.8–8.8 months ) in the control group . Grade 3 or 4 toxicity was documented in 26 ( 68.4 % ) patients in the treatment group , including three neutropenic fever and one death from sepsis , while grade 3 or 4 toxicity occurred in 6 patients ( 15.8 % ) in the control group . The high frequency of serious hematological toxicity with ACNU-CDDP neoadjuvant chemotherapy followed by radiotherapy and adjuvant temozolomide limits its usage as primary treatment for glioblastoma . Future studies should aim to identify a sub population at reduced risk for ACNU-CDDP toxicity so that the potential of this protocol can be realized BACKGROUND In this r and omized phase III study , the effectiveness as well as the side-effects of intraarterial [ i.a . ] ( 17 patients ) versus intravenous [ i.v . ] ( 16 patients ) ACNU [ Nimustine ] administration in newly diagnosed glioblastoma , were compared . PATIENTS AND METHODS All patients undenwent extensive surgical resection , and both groups were homogeneous for the other known risk factors . Thirty-three patients with glioblastoma were treated with ACNU at the dose of 80 - 100 mg/m2 . Treatment was repeated every 5 - 8 weeks for a minimum of 2 and maximum of 14 cycles . Total survival time ( TST ) and to time to progression were chosen as outcome variables . RESULTS AND CONCLUSION No significant differences in systemic and hematological toxicity between the i.a . and iv . ACNU administration routes were detected . In both groups , tolerance of the procedure was excellent . Analysis of the main outcome measured showed no significant differences between i.a . and i.v . ACNU administration : time to progression was 6 months for i.a . ACNU and 4 months for i.v . ACNU and total survival time was 17 months for i.a . ACNU and 20 months for i.v . ACNU . In spite of ACNU dose incrementation , obtained through i.a . route administration , and subsequent higher concentration in the tumor bed , no improvement could be achieved in effectiveness The effect of intratumoral recombinant interferon gamma ( rIFN-gamma ) as adjuvant to open cytoreduction and external irradiation of 60 Gy on survival in adults with a newly diagnosed high- grade cerebral glioma was studied . The patients were r and omised during surgery into the rIFN-gamma group ( n = 14 ) or the control group ( n = 17 ) , and the latter received a subcutaneous reservoir of rIFN-gamma injections . Intratumoral rIFN-gamma was given three times a week for 4 weeks until radiotherapy , escalating the dose from 5 micrograms to 50 micrograms . Both groups received external whole-brain irradiation of 40 Gy and a local boost of 20 Gy . After radiotherapy , rIFN-gamma was continued with 50 micrograms twice a week up to 9 weeks . The patients received no chemotherapy . Intratumoral rIFN-gamma was tolerated well with transient fever only . There were 12 glioblastomas ( GBs ) in the control group and nine in the rIFN-gamma group with completed irradiation . The patients were followed clinical ly and by computerised tomography ( CT ) every third month until death . Tumour responses were seen in three interferon-treated ( one still alive 45 months after operation ) and in two conventionally treated patients . The progression of the tumour volumes on CT did not differ between the IFN-treated and control groups . There were no differences in the survival times . Median survival of the rIFN-gamma-treated patients was 54 weeks ( 95 % CI 35 - 68 ) and of the control patients 55 weeks ( 95 % CI 41 - 77 ) . Intratumoral rIFN-gamma given in the study doses does not seem to inhibit tumour growth or improve the prognosis of patients with high- grade glioma Abstract BACKGROUND : Five-aminolevulinic acid ( 5-ALA ) is used for fluorescence-guided resections of malignant glioma at a dose of 20 mg/kg ; yet , it is unknown whether lower doses may also provide efficacy . OBJECTIVE : To perform a double-blinded r and omized study comparing 3 different doses of 5-ALA . METHODS : Twenty-one patients with suspected malignant glioma were r and omly assigned to 0.2 , 2 , or 20 mg/kg 5-ALA . Investigators were unaware of dose . Intraoperatively , regions of interest were first defined in tumor core , margin , and adjacent white matter under white light . Under violet – blue illumination , the surgeon 's impression of fluorescence was recorded per region , followed by spectrometry and biopsy . Plasma was collected after administration and analyzed for 5-ALA and protoporphyrin IX ( PPIX ) content . RESULTS : The positive predictive value of fluorescence was 100 % . Visual and spectrometric fluorescence assessment Output:	Compared with supportive care only , NMA evidence suggested that all treatments apart from BEV_RT prolonged survival to some extent . When treatments were ranked according to their effects on OS , CRT ranked higher than TMZ , RT and supportive care only , with the latter ranked last . BEV plus RT was the only treatment for which there was no clear benefit in OS over supportive care only . Findings from the trial suggest that the intervention probably improves overall survival in this selected patient population . For elderly people with glioblastoma who are self-caring , evidence suggests that CRT prolongs survival compared with RT and may prolong overall survival compared with TMZ alone . For those undergoing RT or TMZ therapy , there is probably little difference in QoL overall . Systemic anti-cancer treatments TMZ and BEV carry a higher risk of severe haematological and thromboembolic events and CRT is probably associated with a higher risk of these events .
MS212020	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The objective of this study was to determine acceptability and feasibility of patient-based partner referral ( PBPR ) and patient-delivered partner medication ( PDPM ) among female sexually transmitted infection ( STI ) patients in a community-based STI screening study . Women were r and omized to STI screening at home or at a clinic . STI patients could choose between PBPR and PDPM . Six-week follow-up interviews , and in-depth interviews , were conducted . STI prevalence was high . Most of the 106 women with an STI chose PDPM , mainly because partners would not have time or would not want to attend a clinic , and to ensure that partners received treatment . Nearly all partners reportedly took medication ( 94 ; 89 % took it in front of the woman ) or went to a clinic for treatment ( 92 % ) . No adverse events were reported . Good communication emerged as the key to successful partner notification . In conclusion , PDPM could be used as a strategy to improve STI treatment coverage Objective : To measure quality of sexually transmitted disease ( STD ) syndromic case management and aspects of health-seeking behaviour at baseline in an intervention trial . Setting : Ten rural primary care clinics , Hlabisa district , South Africa . Design : Simulated patients ( fieldworkers trained to present with STD syndromes ) made a total of 44 clinic visits ; 49 STD patients were interviewed when exiting clinics ; facilities were assessed for availability of necessary equipment and drugs ; 10 focus group discussion s were held with staff ; and STD syndrome surveillance was performed in all 10 clinics . Results : A total of 9 % of simulated patients were correctly managed ( given correct drugs , plus condoms and partner notification cards ) , recommended drug treatment was given in only 41 % of visits , and appropriate counselling was given in 48 % of visits . Among patients leaving the clinic , although 39 % waited over an hour to be seen and only 37 % were consulted in private , all reported staff attitudes as satisfactory or good . Only six clinics had syndromic management protocol s available , three reported intermittent drug shortages , and seven lacked partner notification cards . Focus group discussion s revealed good staff knowledge about STD , but showed lack of training in syndromic management and low morale . Surveillance data showed that while 75 % of those presenting for care did so within 1 week of symptom onset , 27 % had been treated for an STD in the preceding 3 months , and only 6 % of those treated were contacts . Conclusions : Quality of STD case management was poor despite good staff knowledge and availability of most essential re sources . An intervention comprising staff training and STD syndrome packets has been design ed to improve quality of case management Objectives : To describe important details of the design and operational features of the Mwanza sexually transmitted diseases ( STD ) control programme . To assess the feasibility of the intervention , the distribution of STD syndromes observed , the clinical effectiveness of syndromic STD case management , the utilisation of STD services by the population , and the quality of syndromic STD services delivered at rural health units . Methods : The intervention was integrated into rural primary healthcare ( PHC ) units . It comprised improved STD case management using the syndromic approach , facilitated by a regional programme office which ensured the training of health workers , a reliable supply of effective drugs , and regular support supervision . Five studies were performed to evaluate operational performance : ( i ) a survey of register books to collect data on patients presenting with STDs and reproductive tract infections ( RTIs ) to rural health units with improved STD services , ( ii ) a survey of register books from health units in communities without improved services , ( iii ) a survey of register books from referral clinics , ( iv ) a home based cross sectional study of STD patients who did not return to the intervention health units for follow up , ( v ) a cross sectional survey of reported STD treatment seeking behaviour in a r and om cohort of 8845 adults served by rural health units . Results : During the 2 years of the Mwanza trial , 12 895 STD syndromes were treated at the 25 intervention health units . The most common syndromes were urethral discharge ( 67 % ) and genital ulcers ( 26 % ) in men and vaginal discharge ( 50 % ) , lower abdominal tenderness ( 33 % ) , and genital ulcers ( 13 % ) in women . Clinical treatment effectiveness was high in patients from whom complete follow up data were available , reaching between 81 % and 98 % after first line treatment and 97%–99 % after first , second , and third line treatment . Only 26 % of patients referred to higher levels of health care had presented to their referral institutions . During the trial period , data from the cohort showed that 12.8 % of men and 8.6 % of women in the intervention communities experienced at least one STD syndrome . Based on various approaches , utilisation of the improved health units by symptomatic STD patients in these communities was estimated at between 50 % and 75 % . During the first 6 months of intervention attendance at intervention units increased by 53 % . Thereafter , the average attendance rate was about 25 % higher than in comparison communities . Home visits to 367 non-returners revealed that 89 % had been free of symptoms after treatment , but 28 % became symptomatic again within 3 months of treatment . 100 % of these patients reported that they had received treatment , but only 74 % had been examined , only 57 % had been given health education , and only 30 % were offered condoms . Patients did not fully recall which treatment they had been given , but possibly only 63 % had been treated exactly according to guidelines . Conclusions : This study demonstrated that it is feasible to integrate effective STD services into the existing PHC structure of a developing country . Improved services attract more patients , but additional educational efforts are needed to further improve treatment seeking behaviour . Furthermore , clear treatment guidelines , a reliable drug supply system , and regular supervision are critical . All efforts should be made to treat patients on the spot , without delay , as referral to higher levels of care led to a high number of dropouts . The syndromic approach to STD control should be supported by at least one reference clinic and laboratory per country to ensure monitoring of prevalent aetiologies , of the development of bacterial resistance , and of the effectiveness of the syndromic algorithms in use STUDY OBJECTIVE To assess quality of care of sexually transmitted diseases ( STDs ) and evaluate interactive training methods aim ed at improving providers ' performance . DESIGN AND SETTING This comparative study , with a baseline , intervention , and evaluation phases was conducted at two urban health centers in Zambia . The personnel at one health center were trained in STD management using interactive training methods . The other health center acted as a control . SUBJECTS AND METHODS Two-hundred patients with STD were interviewed and their interaction with health care providers observed before and after the training . Another 200 interviews and observations were conducted at the control health center . RESULTS The proportion of patients being examined , given health education and informed about partner notification increased significantly after the intervention . The proportion of patients who had complaints about the health care did not decrease . Long waiting time and lack of time to discuss the disease were the main complaints . CONCLUSION The training solved some , but not all , problems of poor case management . This indicates the need for a more process-oriented approach for improving quality of care Objective : To explore the role of primary health centers in provision of voluntary counseling and testing ( VCT ) in Kenya . Design and Setting : Prospect i ve service evaluation at 3 ( 1 urban and 2 rural ) government health centers . Subjects : Consecutive adult clients . Main Outcome Measures : Uptake of services , user characteristics , quality of service . Results : Counseling services received 2315 new clients over 26 months . The last quarter averaged 101 clients per clinic . More than 80 % of clients lived locally . Overall 93 % opted to test , 91 % receiving results , 82 % on the same day . Most clients tested HIV negative ( 81 % ) . Youth and men were well represented . Few couples ( 10 % ) attended . Seventeen percent of women were pregnant . Self-referral was common and illness was an uncommon reason for testing ( < 20 % ) . Thirty-one percent of clients were referred from VCT to other health center services . Counseling was perceived as high quality by users and providers . Validation of the test algorithm showed a sensitivity of 98.0 % and specificity of 98.7 % . Conclusion : Government health centers in Kenya can be appropriate providers of VCT . This pilot helped initiate a new strategy of health center-based VCT in Kenya and this has facilitated rapid expansion and more equitable provision for Kenyans Unlike contact-tracing procedures for syphilis and gonorrhea , field follow-up to locate and treat patients with Chlamydia trachomatis infections has not been extensively applied in the United States . We implemented two studies to assess the efficiency and cost-effectiveness of using field follow-up for contact of two groups : patients with chlamydial infection detected as part of a screening program and women who were sexual partners of men with nongonococcal urethritis ( NGU ) . Of the 142 patients with chlamydial infection who had not been treated empirically , 112 ( 79 % ) returned for treatment when a reminder system was used , as compared with a return rate of 97 % ( 259/266 ) achieved by field follow-up ( P less than 0.0001 ) . Among the 678 men with NGU enrolled in a r and omized trial of field follow-up vs. two self-referral methods , field follow-up yielded over three times as many partners returning to the clinic for treatment as did either of the other two methods ( P less than 0.001 ) . Analyses using the estimated costs of the intervention strategies and the medical costs associated with an untreated chlamydial infection showed that field follow-up by trained investigators proved to be not only the most efficient method for locating patients with chlamydial infection and /or patients who were at risk for it , but also the most cost-effective in terms of total health-care dollars spent BACKGROUND Treatment of sexually-transmitted infections ( STIs ) and behavioural interventions are the main methods to prevent HIV in developing countries . We aim ed to assess the effect of these interventions on incidence of HIV-1 and other sexually-transmitted infections . METHODS We r and omly allocated all adults living in 18 communities in rural Ug and a to receive behavioural interventions alone ( group A ) , behavioural and STI interventions ( group B ) , or routine government health services and community development activities ( group C ) . The primary outcome was HIV-1 incidence . Secondary outcomes were incidence of herpes simplex virus type 2 ( HSV2 ) and active syphilis and prevalence of gonorrhoea , chlamydia , reported genital ulcers , reported genital discharge , and markers of behavioural change . Analysis was per protocol . FINDINGS Compared with group C , the incidence rate ratio of HIV-1 was 0.94 ( 0.60 - 1.45 , p=0.72 ) in group A and 1.00 ( 0.63 - 1.58 , p=0.98 ) in group B , and the prevalence ratio of use of condoms with last casual partner was 1.12 ( 95 % CI 0.99 - 1.25 ) in group A and 1.27 ( 1.02 - 1.56 ) in group B. Incidence of HSV2 was lower in group A than in group C ( incidence rate ratio 0.65 , 0.53 - 0.80 ) and incidence of active syphilis for high rapid plasma reagent test titre and prevalence of gonorrhoea were both lower in group B than in group C ( active syphilis incidence rate ratio , 0.52 , 0.27 - 0.98 ; gonorrhoea prevalence ratio , 0.25 , 0.10 - 0.64 ) . INTERPRETATION The interventions we used were insufficient to reduce HIV-1 incidence in rural Ug and a , where secular changes are occurring . More effective STI and behavioural interventions need to be developed for HIV control in mature epidemics Background Patient-based partner referral ( PBPR ) , which is the main method for treating sexual partners of patients with sexually transmitted diseases ( STDs ) , has limited effectiveness . Goal The authors compared the efficacy of PBPR with patient-delivered partner medication ( PDPM ) among patients attending the Mulago STD clinic in Kampala , Ug and a. Study Design A total of 383 patients ( 187 women , 196 men ) with STDs were r and omized to the PBPR or PDPM group . The proportion of sexual partners treated in either group was compared using the chi-square statistic by intention to treat for partners whose follow-up status was unknown . Results The two groups had similar background characteristics . Of the 237 partners elicited , 176 ( 74 % ) were reported treated in the PDPM group . In the PBPR group , in which 234 partners were elicited , 79 ( 34 % ) were referred to the treatment clinic . This difference was statistically significant ( risk ratio [ RR ] , 2.44 ; 95 % CI , 1.95–3.07;P < 0.001 ) . Furthermore , PDPM was more effective than PBPR for women and for casual partners for whom PBPR is considered difficult . For women , 86 of 103 partners in the PDPM group were reported treated , compared with 23 of 104 partners in the PBPR group ( RR , 4.55 ; 95 % CI , 2.92–7.08;P < 0.001 ) . For casual partners , 18 of 51 ( 34 % ) were reported treated in the PDPM group , compared with only three of 45 partners ( 7 % ) who were Output:	Reported barriers included sociocultural factors such as stigma , fear of abuse for having an STI , and infrastructural factors related to the limited number of STD clinics , and trained providers and reliable diagnostic methods . Client-oriented counselling was found to be effective in improving partner referral outcomes . Conclusions STD clinics can improve PN with client-oriented counselling , which should help clients to overcome perceived barriers .
MS212021	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Nasal carriers of Staphylococcus aureus are at increased risk for health care-associated infections with this organism . Decolonization of nasal and extranasal sites on hospital admission may reduce this risk . METHODS In a r and omized , double-blind , placebo-controlled , multicenter trial , we assessed whether rapid identification of S. aureus nasal carriers by means of a real-time polymerase-chain-reaction ( PCR ) assay , followed by treatment with mupirocin nasal ointment and chlorhexidine soap , reduces the risk of hospital-associated S. aureus infection . RESULTS From October 2005 through June 2007 , a total of 6771 patients were screened on admission . A total of 1270 nasal swabs from 1251 patients were positive for S. aureus . We enrolled 917 of these patients in the intention-to-treat analysis , of whom 808 ( 88.1 % ) underwent a surgical procedure . All the S. aureus strains identified on PCR assay were susceptible to methicillin and mupirocin . The rate of S. aureus infection was 3.4 % ( 17 of 504 patients ) in the mupirocin-chlorhexidine group , as compared with 7.7 % ( 32 of 413 patients ) in the placebo group ( relative risk of infection , 0.42 ; 95 % confidence interval [ CI ] , 0.23 to 0.75 ) . The effect of mupirocin-chlorhexidine treatment was most pronounced for deep surgical-site infections ( relative risk , 0.21 ; 95 % CI , 0.07 to 0.62 ) . There was no significant difference in all-cause in-hospital mortality between the two groups . The time to the onset of nosocomial infection was shorter in the placebo group than in the mupirocin-chlorhexidine group ( P=0.005 ) . CONCLUSIONS The number of surgical-site S. aureus infections acquired in the hospital can be reduced by rapid screening and decolonizing of nasal carriers of S. aureus on admission . ( Current Controlled Trials number , IS RCT N56186788 . BACKGROUND Intensive care units ( ICUs ) are high-risk setting s for the transmission of methicillin-resistant Staphylococcus aureus ( MRSA ) and vancomycin-resistant enterococcus ( VRE ) . METHODS In a cluster-r and omized trial , we evaluated the effect of surveillance for MRSA and VRE colonization and of the exp and ed use of barrier pre caution s ( intervention ) as compared with existing practice ( control ) on the incidence of MRSA or VRE colonization or infection in adult ICUs . Surveillance cultures were obtained from patients in all participating ICUs ; the results were reported only to ICUs assigned to the intervention . In intervention ICUs , patients who were colonized or infected with MRSA or VRE were assigned to care with contact pre caution s ; all the other patients were assigned to care with universal gloving until their discharge or until surveillance cultures obtained at admission were reported to be negative . RESULTS During a 6-month intervention period , there were 5434 admissions to 10 intervention ICUs , and 3705 admissions to 8 control ICUs . Patients who were colonized or infected with MRSA or VRE were assigned to barrier pre caution s more frequently in intervention ICUs than in control ICUs ( a median of 92 % of ICU days with either contact pre caution s or universal gloving [ 51 % with contact pre caution s and 43 % with universal gloving ] in intervention ICUs vs. a median of 38 % of ICU days with contact pre caution s in control ICUs , P<0.001 ) . In intervention ICUs , health care providers used clean gloves , gowns , and h and hygiene less frequently than required for contacts with patients assigned to barrier pre caution s ; when contact pre caution s were specified , gloves were used for a median of 82 % of contacts , gowns for 77 % of contacts , and h and hygiene after 69 % of contacts , and when universal gloving was specified , gloves were used for a median of 72 % of contacts and h and hygiene after 62 % of contacts . The mean ( ±SE ) ICU-level incidence of events of colonization or infection with MRSA or VRE per 1000 patient-days at risk , adjusted for baseline incidence , did not differ significantly between the intervention and control ICUs ( 40.4±3.3 and 35.6±3.7 in the two groups , respectively ; P=0.35 ) . CONCLUSIONS The intervention was not effective in reducing the transmission of MRSA or VRE , although the use of barrier pre caution s by providers was less than what was required . ( Funded by the National Institute of Allergy and Infectious Diseases and others ; STAR*ICU Clinical Trials.gov number , NCT00100386 . ) INTRODUCTION Preoperative nasal mupirocin has been shown to reduce surgical site infections ( SSIs ) in patients undergoing cardiac surgery . We analyzed the effect of mupirocin plus antiseptic body wash on SSI rate and etiology . METHODS Prospect i ve SSI surveillance was done for patients undergoing cardiac surgery before and after implementation of mupirocin nasal ointment and chlorhexidine/octenidine body wash . RESULTS Overall SSI rate was 8.6 % ( 81 out of 945 ) for the control and 6.9 % ( 58 out of 842 ) for the intervention cohort ( P = .19 ) . In multivariable analysis , the study protocol was associated with an odds ratio of 0.61 ( 95 % confidence interval , 0.41 - 0.91 ; P = .015 ) with regard to any SSI . This effect was exclusively due to a reduction in superficial SSIs and was observed both in patients with preoperative and postoperative treatment initiation . Coagulase-negative staphylococci ( CoNS ) , the most commonly isolated pathogen , were found in 37 % and 48 % ( P = .19 ) of patients in the control and the intervention cohort , respectively . CoNS were methicillin resistant in 69 % of cases . CONCLUSIONS Mupirocin and antiseptic body wash reduced the rate of superficial but not deep or organ/space SSIs . Postoperative patient treatment may be critical in reducing the risk for superficial SSI , presumably due to a reduction of bacterial skin load . A high proportion of SSI was due to methicillin-resistant CoNS and thus not covered by routine perioperative antimicrobial prophylaxis CONTEXT Nosocomial infections are an important cause of morbidity and mortality after cardiac surgery . Decolonization of endogenous potential pathogenic microorganisms is important in the prevention of nosocomial infections . OBJECTIVE To determine the efficacy of perioperative decontamination of the nasopharynx and oropharynx with 0.12 % chlorhexidine gluconate for reduction of nosocomial infection after cardiac surgery . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve , r and omized , double-blind , placebo-controlled clinical trial conducted at the Onze Lieve Vrouwe Gasthuis , Amsterdam , the Netherl and s , between August 1 , 2003 , and September 1 , 2005 . Of 991 patients older than 18 years undergoing elective cardiothoracic surgery during the study interval , 954 were eligible for analysis . INTERVENTION Oropharyngeal rinse and nasal ointment containing either chlorhexidine gluconate or placebo . MAIN OUTCOME MEASURES Incidence of nosocomial infection , in addition to the rate of Staphylococcus aureus nasal carriage and duration of hospital stay . RESULTS The incidence of nosocomial infection in the chlorhexidine gluconate group and placebo group was 19.8 % and 26.2 % , respectively ( absolute risk reduction [ ARR ] , 6.4 % ; 95 % confidence interval [ CI ] , 1.1%-11.7 % ; P = .002 ) . In particular , lower respiratory tract infections and deep surgical site infections were less common in the chlorhexidine gluconate group than in the placebo group ( ARR , 6.5 % ; 95 % CI , 2.3%-10.7 % ; P = .002 ; and 3.2 % ; 95 % CI , 0.9%-5.5 % ; P = .002 , respectively ) . For the prevention of 1 nosocomial infection , 16 patients needed to be treated with chlorhexidine gluconate . A significant reduction of 57.5 % in S aureus nasal carriage was found in the chlorhexidine gluconate group compared with a reduction of 18.1 % in the placebo group ( P<.001 ) . Total hospital stay for patients treated with chlorhexidine gluconate was 9.5 days compared with 10.3 days in the placebo group ( ARR , 0.8 days ; 95 % CI , 0.24 - 1.88 ; P = .04 ) . CONCLUSION Decontamination of the nasopharynx and oropharynx with chlorhexidine gluconate appears to be an effective method to reduce nosocomial infection after cardiac surgery . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00272675 BACKGROUND Both targeted decolonization and universal decolonization of patients in intensive care units ( ICUs ) are c and i date strategies to prevent health care-associated infections , particularly those caused by methicillin-resistant Staphylococcus aureus ( MRSA ) . METHODS We conducted a pragmatic , cluster-r and omized trial . Hospitals were r and omly assigned to one of three strategies , with all adult ICUs in a given hospital assigned to the same strategy . Group 1 implemented MRSA screening and isolation ; group 2 , targeted decolonization ( i.e. , screening , isolation , and decolonization of MRSA carriers ) ; and group 3 , universal decolonization ( i.e. , no screening , and decolonization of all patients ) . Proportional-hazards models were used to assess differences in infection reductions across the study groups , with clustering according to hospital . RESULTS A total of 43 hospitals ( including 74 ICUs and 74,256 patients during the intervention period ) underwent r and omization . In the intervention period versus the baseline period , modeled hazard ratios for MRSA clinical isolates were 0.92 for screening and isolation ( crude rate , 3.2 vs. 3.4 isolates per 1000 days ) , 0.75 for targeted decolonization ( 3.2 vs. 4.3 isolates per 1000 days ) , and 0.63 for universal decolonization ( 2.1 vs. 3.4 isolates per 1000 days ) ( P=0.01 for test of all groups being equal ) . In the intervention versus baseline periods , hazard ratios for bloodstream infection with any pathogen in the three groups were 0.99 ( crude rate , 4.1 vs. 4.2 infections per 1000 days ) , 0.78 ( 3.7 vs. 4.8 infections per 1000 days ) , and 0.56 ( 3.6 vs. 6.1 infections per 1000 days ) , respectively ( P<0.001 for test of all groups being equal ) . Universal decolonization result ed in a significantly greater reduction in the rate of all bloodstream infections than either targeted decolonization or screening and isolation . One bloodstream infection was prevented per 54 patients who underwent decolonization . The reductions in rates of MRSA bloodstream infection were similar to those of all bloodstream infections , but the difference was not significant . Adverse events , which occurred in 7 patients , were mild and related to chlorhexidine . CONCLUSIONS In routine ICU practice , universal decolonization was more effective than targeted decolonization or screening and isolation in reducing rates of MRSA clinical isolates and bloodstream infection from any pathogen . ( Funded by the Agency for Healthcare Research and the Centers for Disease Control and Prevention ; REDUCE MRSA Clinical Trials.gov number , NCT00980980 ) BACKGROUND Surgical site infection has been identified as one of the most important preventable sources of morbidity and mortality associated with medical treatment . The purpose of the present study was to evaluate the feasibility and efficacy of an institutional prescreening program for the preoperative detection and eradication of both methicillin-resistant and methicillin-sensitive Staphylococcus aureus in patients undergoing elective orthopaedic surgery . METHODS Data were collected prospect ively during a single-center study . A universal prescreening program , employing rapid polymerase chain reaction analysis of nasal swabs followed by an eradication protocol of intranasal mupirocin and chlorhexidine showers for identified carriers , was implemented . Surgical site infection rates were calculated and compared with a historical control period immediately preceding the start of the screening program . RESULTS During the study period , 7019 of 7338 patients underwent preoperative screening before elective surgery , for a successful screening rate of 95.7 % . One thous and five hundred Output:	RESULTS Decolonization with topical chlorhexidine and intranasal mupirocin result ed in reduction of S aureus SSI and methicillin-resistant S aureus nosocomial infection and eradication of S aureus nasal carriage . CONCLUSION The results of this review indicate the combination of topical chlorhexidine and intranasal mupirocin is effective in reducing S aureus-associated SSIs
MS212022	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Antibiotic-associated diarrhea ( AAD ) is a common complication of antibiotic use . There is growing interest in probiotics for the treatment of AAD and Clostridium difficile infection because of the wide availability of probiotics . The aim of this multicenter , r and omized , placebo-controlled , double-blind trial was to assess the efficacy of probiotic Lactobacillus ( Lacidofil ® cap ) for the prevention of AAD in adults . From September 2008 to November 2009 , a total of 214 patients with respiratory tract infection who had begun receiving antibiotics were r and omized to receive Lactobacillus ( Lacidofil ® cap ) or placebo for 14 days . Patients recorded bowel frequency and stool consistency daily for 14 days . The primary outcome was the proportion of patients who developed AAD within 14 days of enrollment . AAD developed in 4 ( 3.9 % ) of 103 patients in the Lactobacillus group and in 8 ( 7.2 % ) of 111 patients in the placebo group ( P=0.44 ) . However , the Lactobacillus group showed lower change in bowel frequency and consistency ( 50/103 , 48.5 % ) than the placebo group ( 35/111 , 31.5 % ) ( P=0.01 ) . Although the Lacidofil ® cap does not reduce the rate of occurrence of AAD in adult patients with respiratory tract infection who have taken antibiotics , the Lactobacillus group maintains their bowel habits to a greater extent than the placebo group Abstract Objective . The effect of probiotics on IBS symptoms has been mixed , but remains an intriguing treatment option with appeal to the patient . Material and methods . Patients fulfilling the Rome II criteria were r and omized double-blind to a daily intake of 500 ml of fermented milk containing at least 5 × 107 CFU/ml of Lactobacillus paracasei ssp paracasei F19 , Lactobacillus acidophilus La5 and Bifidobacterium lactis Bb12 or an equal volume of acidified milk for 8 weeks . Symptoms were assessed at baseline and weekly using a disease-specific vali date d symptom rating scale ( IBS-SSI ) . The predefined primary outcome measure was patient reported adequate symptom relief . Adherence to study protocol were assessed by performing stool sample s at the of the treatment period . Results . Eight-one patients were screened . Sixty-four patients were r and omized ; 18 patients did not complete the study due to protocol violations or withdrew due to lack of effect . Fifty-two patients ( 13 males ) completed the study as per protocol ; mean age was 51.3 years ( range 29–67 ) . The proportion of patients reporting adequate symptom relief increased in both patient groups , but there was not any statistical difference between the groups . IBS-SSI scores did not differ statistically between the groups at the end of the treatment period , but improved during the study period in both groups . Conclusions . During this 8-week trial gastrointestinal symptoms improved . However , there was no difference between treatment with fermented milk containing probiotics or acidified milk . The effect of probiotics on IBS symptoms remains uncertain and further studies are warranted Background Probiotics purportedly reduce symptoms of gastrointestinal and upper respiratory-tract illness by modulating commensal microflora . Preventing and reducing symptoms of respiratory and gastrointestinal illness are the primary reason that dietary supplementation with probiotics are becoming increasingly popular with healthy active individuals . There is a paucity of data regarding the effectiveness of probiotics in this cohort . The aim of this study was to evaluate the effectiveness of a probiotic on faecal microbiology , self-reported illness symptoms and immunity in healthy well trained individuals . Methods Competitive cyclists ( 64 males and 35 females ; age 35 ± 9 and 36 ± 9 y , VO2max 56 ± 6 and 52 ± 6 ml.kg-1.min-1 , mean ± SD ) were r and omised to either probiotic ( minimum 1 × 109Lactobacillus fermentum ( PCC ® ) per day ) or placebo treatment for 11 weeks in a double-blind , r and omised , controlled trial . The outcome measures were faecal L. fermentum counts , self-reported symptoms of illness and serum cytokines . Results Lactobacillus numbers increased 7.7-fold ( 90 % confidence limits 2.1- to 28-fold ) more in males on the probiotic , while there was an unclear 2.2-fold ( 0.2- to 18-fold ) increase in females taking the probiotic . The number and duration of mild gastrointestinal symptoms were ~2-fold greater in the probiotic group . However , there was a substantial 0.7 ( 0.2 to 1.2 ) of a scale step reduction in the severity of gastrointestinal illness at the mean training load in males , which became more pronounced as training load increased . The load ( duration ×severity ) of lower respiratory illness symptoms was less by a factor of 0.31 ( 99%CI ; 0.07 to 0.96 ) in males taking the probiotic compared with placebo but increased by a factor of 2.2 ( 0.41 to 27 ) in females . Differences in use of cold and flu medication mirrored these symptoms . The observed effects on URTI had too much uncertainty for a decisive outcome . There were clear reductions in the magnitude of acute exercise-induced changes in some cytokines . Conclusion L. fermentum may be a useful nutritional adjunct for healthy exercising males . However , uncertainty in the effects of supplementation on URTI and on symptoms in females needs to be resolved . Trial registration The trial was registered in the Australia and New Zeal and Clinical Trials Registry ( ACTRN12611000006943 ) Background and aims Meta-analyses point to a modest but significant effect of probiotics on symptoms in irritable bowel syndrome ( IBS ) . We aim ed to assess the effect of the probiotic Lactobacillus casei Shirota ( LcS ) on symptoms and quality of life in IBS patients in a r and omized , double-blind , placebo-controlled intervention study . Material s and methods IBS patients ( Rome II ) between 18 and 65 years of age were included . The study consisted of an 8-week intervention period in which the participants received probiotic ( LcS ) or placebo twice daily , followed by an 8-week follow-up period . Symptom diaries and quality of life were scored at weeks 0 , 8 and 16 . The primary outcome parameter was a decrease of at least 30 % in a composite mean symptom score ( MSS ) at week 8 on the basis of an intention-to-treat analysis . Results Thirty-nine individuals ( 67 % women ) were included in the probiotic group and 41 individuals ( 71 % women ) were included in the placebo group . After the intervention period , the mean relative improvement did not reach 30 % for MSS or any individual symptom score . After follow-up ( week 16 ) , a mean improvement of at least 30 % was achieved for MSS in the probiotic group , but no significant difference was found between both treatment groups ( mean±SD : 34±7 % ; 13±8 % , P=0.06 ) . Conclusion After probiotic treatment with LcS , no improvement of 30 % in MSS was observed after 8 weeks AIMS To clarify the effects of Lactobacillus gasseri CP2305 ( CP2305 ) on quality of life and clinical symptoms and its functional mechanisms in patients with irritable bowel syndrome ( IBS ) . METHODS AND RESULTS After the patients were administered CP2305 daily for 4 weeks , the IBS-severity index score was significantly improved compared with that of the placebo group , and this improvement was accompanied by a reduction in health-related worry and changes in intestinal microbiota . The gene expression profiling of the peripheral blood leucocytes showed that CP2305 treatment significantly up-regulated genes related to eukaryotic initiation factor 2 ( EIF2 ) signalling . Eighty-two genes were down-regulated in IBS patients compared with healthy controls . The expression of 23 of these genes exhibited a CP2305-dependent increase associated with an improvement in IBS severity . The majority of the restored genes were related to EIF2 signalling . CONCLUSIONS CP2305 administration is a potential c and i date therapeutic option for patients with IBS . SIGNIFICANCE AND IMPACT OF THE STUDY Although probiotics have been proposed to benefit IBS patients , objective clinical evidence and elucidation of the functional mechanism remain insufficient . Our study demonstrated that CP2305 administration beneficially influences IBS patients in both subjective and objective evaluations , and gene expression profiling provided insights into the functional mechanism AIM To evaluate the effects of a combination probiotic on symptoms and colonic transit in patients with irritable bowel syndrome ( IBS ) and significant bloating . METHODS Forty-eight patients with Rome II IBS were r and omized in a parallel group , double-blind design to placebo or VSL # 3 twice daily ( 31 patients received 4 weeks and 17 patients 8 weeks of treatment ) . Pre- and post-treatment colonic transit measurements were performed using scintigraphy with (111)In charcoal . Symptoms were summarized as an average daily score for the entire period of treatment and separately for the first 4 weeks of treatment . Weekly satisfactory relief of abdominal bloating was assessed . RESULTS Treatment with VSL # 3 was associated with reduced flatulence over the entire treatment period ( placebo 39.5 + /- 2.6 vs VSL # 3 29.7 + /- 2.6 , P = 0.011 ) ; similarly , during the first 4 weeks of treatment , flatulence scores were reduced ( placebo 40.1 + /- 2.5 vs VSL # 3 30.8 + /- 2.5 , P = 0.014 ) . Proportions of responders for satisfactory relief of bloating , stool-related symptoms , abdominal pain and bloating scores were not different . Colonic transit was retarded with VSL # 3 relative to placebo ( colon geometric center 2.27 + /- 0.20 vs 2.83 + /- 0.19 , P = 0.05 respectively ) . CONCLUSION VSL # 3 reduces flatulence scores and retards colonic transit without altering bowel function in patients with IBS and bloating AIM To determine the effects of Lactobacillus acidophilus NCFM on irritable bowel syndrome ( IBS ) symptoms and quality of life ( QoL ) . METHODS In this r and omized triple-blind trial , adult IBS volunteers who were recruited according to Rome III criteria received 109 or 1010 colony-forming units of NCFM or placebo daily for 12 wk . IBS Symptom Severity Score ( IBS-SSS ) , which constituted the primary outcome , and secondary outcomes , including individual IBS symptoms , IBS-related QoL question naire , anxiety and depression , defecation frequency , and stool consistency , were assessed at baseline at the end of the 8-wk run-in period , after 4 and 12 wk of intervention , and after a 4-wk washout . RESULTS A total of 340 of 391 r and omized volunteers completed the trial . IBS-SSS improved over 12 wk of treatment in all treatment groups , decreasing by a mean ± SD of 44.0 ± 80.2 , 50.8 ± 82.4 , and 48.3 ± 72.2 in the placebo , active low-dose , and active high-dose groups , respectively . Similarly , secondary outcomes did not differ between treatment groups . However , in a post hoc analysis of volunteers with moderate to severe abdominal pain at baseline ( VAS > 35/100 ) , the treatment significantly reduced the sensation of abdominal pain . Pain scores fell by 20.8 ± 22.8 , 29.4 ± 17.9 , and 31.2 ± 21.9 in the placebo , active low-dose , and active high-dose groups , respectively ( P value for placebo vs combined active doses = 0.0460 ) . CONCLUSION NCFM alleviates moderate to severe abdominal pain , consistent with earlier observations of this strain mitigating visceral pain through increased analgesic receptor expression Background This r and omized double blind placebo controlled dual site clinical trial compared a probiotic dietary supplement to placebo regarding effects on gastrointestinal symptoms in adults with post-pr and ial intestinal gas-related symptoms ( abdominal pain , distention , flatulence ) but no gastrointestinal ( GI ) diagnoses to explain the symptoms . Methods Sixty-one adults were enrolled ( age 36.5 ± 12.6 years ; height 165.1 ± 9.2 cm ; weight 75.4 ± 17.3 kg ) and r and omized to either Digestive Advantage ™ Gas Defense Formula - ( GanedenBC30Bacillus coagulans GBI-30 , 6086 ) : n = 30 ; or Placebo : n = 31 . Study subjects were evaluated every two weeks over a four-week period using vali date d question naires and st and ard biochemical safety testing . Outcome criteria of interest included change from baseline in Gastrointest Output:	Consensus statements with 100 % agreement and " high " evidence level indicated that specific probiotics help reduce overall symptom burden and abdominal pain in some patients with IBS and duration /intensity of diarrhoea in patients prescribed antibiotics or H. pylori eradication therapy , and have favourable safety . Statements with 70%-100 % agreement and " moderate " evidence indicated that , in some patients with IBS , specific probiotics help reduce bloating/distension and improve bowel movement frequency/consistency . CONCLUSIONS This up date d review indicates that specific probiotics are beneficial in certain lower GI problems , although many of the new publications did not report benefits of probiotics , possibly due to inclusion of new , less efficacious preparations . Specific probiotics can relieve lower GI symptoms in IBS , prevent diarrhoea associated with antibiotics and H. pylori eradication therapy , and show favourable safety .
MS212023	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Zambia ’s national HIV testing algorithm specifies use of two rapid blood based antibody assays , Determine ® HIV-1/2 ( Inverness Medical ) and if positive then Uni-GoldTM Recombigen HIV-1/2 ( Trinity Biotech ) . Little is known about the performance of oral fluid based HIV testing in Zambia . The aims of this study are two-fold : 1 ) to compare the diagnostic accuracy ( sensitivity and specificity ) under field conditions of the OraQuick ® ADVANCE ® Rapid HIV-1/2 ( OraSure Technologies , Inc. ) to two blood-based rapid antibody tests currently in use in the Zambia National Algorithm , and 2 ) to perform a cost analysis of large-scale field testing employing the OraQuick ® . Methods This was a operational retrospective research of HIV testing and question naire data collected in 2010 as part of the ZAMSTAR ( Zambia South Africa TB and AIDS reduction ) study . R and omly sample d individuals in twelve communities were tested consecutively with OraQuick ® test using oral fluid versus two blood-based rapid HIV tests , Determine ® and Uni-GoldTM . A cost analysis of four algorithms from health systems perspective were performed : 1 ) Determine ® and if positive , then Uni-GoldTM ( Determine ® /Uni-GoldTM ) ; based on current algorithm , 2 ) Determine ® and if positive , then OraQuick ® ( Determine ® /OraQuick ® ) , 3 ) OraQuick ® and if positive , then Determine ® ( OraQuick ® /Determine ® ) , 4 ) OraQuick ® and if positive , then Uni-GoldTM ( OraQuick ® /Uni-GoldTM ) . This information was then used to construct a model using a hypothetical population of 5,000 persons with varying prevalence of HIV infection from 1–30 % . Results 4,458 participants received both a Determine ® and OraQuick ® test . The sensitivity and specificity of the OraQuick ® test were 98.7 ( 95%CI , 97.5–99.4 ) and 99.8 ( 95%CI , 99.6–99.9 ) , respectively when compared to HIV positive serostatus . The average unit costs per algorithm were US$ 3.76 , US$ 4.03 , US$ 7.35 , and US$ 7.67 for Determine ® /Uni-GoldTM , Determine ® /OraQuick ® , OraQuick ® /Determine ® , and OraQuick ® /Uni-GoldTM , respectively , for an HIV prevalence of 15 % . Conclusions An alternative HIV testing algorithm could include OraQuick ® test which had a high sensitivity and specificity . The current Determine ® /Uni-GoldTM testing algorithm is the least expensive when compared to Determine ® /OraQuick ® , OraQuick ® /Determine ® , and OraQuick ® /Uni-GoldTM in the Zambian setting . From our field experience , oral fluid based testing offers many advantages over blood-based testing , especially with self testing on the horizon Background Despite the substantial investment for providing HIV counselling and testing ( VCT ) services in Zambia , there has been little effort to systematic ally evaluate the quality of VCT services provided by various types of health providers . This study , conducted in 2009 , examines VCT in the public and private sectors including private for-profit and NGO/faith-based sectors in Copperbelt and Luapula . Methods The study used five primary data collection methods to gauge quality of VCT services : closed-ended client interviews with clients exiting VCT sites ; open-ended client interviews ; interviews with facility managers ; review of service statistics ; and an observation of the physical environment for VCT by site . Over 400 clients and 87 facility managers were interviewed from almost 90 facilities . Sites were r and omly selected and results are generalizable at the provincial level . Results The study shows concerning levels of underperformance in VCT services across the sectors . It reveals serious underperformance in counselling about key risk-reduction methods . Less than one-third of clients received counselling on reducing number of sexual partners and only approximately 5 % of clients received counselling about disclosing test results to partners . In terms of client profiles , the NGO sector attracts the most educated clients and less educated Zambians seek VCT services at very low rates ( 7 % ) . The private for-profit performs equally or sometimes better than other sectors even though this sector is not adequately integrated into the Zambian national response to HIV . Conclusion The private for-profit sector provides VCT services on par in quality with the other sectors . Most clients did not receive counselling on partner reduction or disclosure of HIV test results to partners . In a generalized HIV epidemic where multiple concurrent sexual partners are a significant problem for transmitting the disease , risk-reduction methods and discussion should be a main focus of pre-test and post-test counselling This paper explores the effect of social relations and gender-based conflicts on the uptake of HIV testing in the South and Central provinces of Zambia . We conducted a community-based cross-sectional study of 1716 r and omly selected individuals . Associations were examined using mixed-effect multivariable logistic regression . A total of 264 men ( 64 % ) and 268 women ( 56 % ) had never tested for HIV . The strongest determinants for not being tested were disruptive couple relationships ( OR = 2.48 95 % CI = 1.00–6.19 ) ; tolerance to gender-based violence ( OR = 2.10 95 % CI = 1.05–4.32 ) and fear of social rejection ( OR = 1.48 95 % CI = 1.23–1.80 ) . In the Zambian context , unequal power relationships within the couple and the community seem to play a pivotal role in the decision to test which until now have been largely underestimated . Policies , programs and interventions to rapidly increase HIV testing need to urgently address gender-power inequity in relationships and prevent gender-based violence to reduce the negative impact on the lives of couples and families Background Across sub-Saharan Africa , men 's levels of HIV-testing remain inadequate relative to women ’s . Men are less likely to access anti-retroviral therapy and experience higher levels of morbidity and mortality once initiated on treatment . More frequent HIV-testing by men at continued risk of HIV-infection is required to facilitate earlier diagnosis . This study explored the frequency of HIV-testing among a rural population of men and the factors associated with more frequent HIV-testing . Methods We conducted a secondary analysis of a population -based survey in three rural district in Zambia , from February-November , 2013 . Households ( N = 300 ) in r and omly selected squares from 42 study sites , defined as a health facility and its catchment area , were invited to participate . Individuals in eligible households were invited to complete question naires regarding demographics and HIV-testing behaviours . Men were defined as multiple HIV-testers if they reported more than one lifetime test . Upon question naire completion , individuals were offered rapid home-based HIV-testing . Results Of the 2376 men , more than half ( 61 % ) reported having ever-tested for HIV . The median number of lifetime tests was 2 ( interquartile range = 1 - 3 ) . Just over half ( n = 834 ; 57 % ) of ever-testers were defined as multiple-testers . Relative to never-testers , multiple-testers had higher levels of education and were more likely to report an occupation . Among the 719 men linked to a spouse , multiple-testing was higher among men whose spouse reported ever-testing ( adjusted prevalence ratio = 3.02 95 % CI : 1.37 - 4.66 ) . Multiple-testing was higher in study sites where anti-retroviral therapy was available at the health facility on the day of a health facility audit . Among ever-testers , education and occupation were positively associated with multiple-testing relative to reporting one lifetime HIV-test . Almost half ( 49 % ) of ever-testers accepted the offer of home-based HIV-testing . Discussion Reported HIV-testing increased among this population of men since a 2011/12 survey . Yet , only 35 % of all men reported multiple lifetime HIV-tests . The factors associated with multiple HIV-testing were similar to factors associated with ever-testing for HIV . Men living with HIV were less likely to report multiple HIV-tests and employment and education were associated with multiple-testing . The offer of home-based HIV-testing increased the frequency of HIV-testing among men . Conclusion Although men 's levels of ever-testing for HIV have increased , strategies need to increase the lifetime frequency of HIV-testing among men at continued risk of HIV-infection Background We assessed the integration of early infant HIV diagnosis with the exp and ed programme for immunization in a rural Zambian setting with the aim of determining whether infant and postpartum maternal HIV testing rates would increase without harming immunization uptake . Methods In an unblinded , location stratified , cluster r and omised controlled trial , 60 facilities in Zambia ’s Southern Province were equally allocated to a control group , Simple Intervention group that received a sensitization meeting and the resupply of HIV testing commodities in the event of a stock-out , and a Comprehensive Intervention group that received the Simple Intervention as well as on-site operational support to facilitate the integration of HIV testing services with EPI . Findings The average change in number of first dose diphtheria , pertussis , and tetanus vaccine ( DPT1 ) provided per month , per facility was approximately 0.86 doses higher [ 90 % confidence interval ( CI ) -1.40 , 3.12 ] in Comprehensive Intervention facilities compared to the combined average change in the Simple Intervention and control facilities . The interventions result ed in a 16.6 % [ 90 % CI : -7 % , 46 % , P-value = 0.26 ] and 10 % [ 90 % CI : -10 % , 36 % , P-value = 0.43 ] greater change in average monthly infant DBS testing compared to control for the Simple and Comprehensive facilities respectively . We also found 15.76 ( 90 % CI : 7.12 , 24.41 , P-value < 0.01 ) and 10.93 ( 90 % CI : 1.52 , 20.33 , P-value = 0.06 ) additional total maternal re-tests over baseline for the Simple and Comprehensive Facilities respectively . Conclusions This study provides strong evidence to support Zambia ’s policy of integration of HIV testing and EPI services . Actions in line with the interventions , including HIV testing material supply reinforcement , can increase HIV testing rates without harming immunization uptake . In response , Zambia ’s Ministry of Health issued a memo to remind health facilities to provide HIV testing at under-five clinics and to include under-five HIV testing as part of district performance assessment s. Trial Registration Clinical Trials.gov Registration Number : Home-based voluntary HIV counselling and testing ( HB-VCT ) has been reported to have a high uptake , but it has not been rigorously evaluated . We design ed a model for HB-VCT appropriate for wider scale-up , and investigated the acceptance of home-based counselling and testing , equity in uptake and negative life events with a cluster-r and omized trial . Thirty six rural clusters in southern Zambia were pair-matched based on baseline data and r and omly assigned to the intervention or the control arm . Both arms had access to st and ard HIV testing services . Adults in the intervention clusters were offered HB-VCT by local lay counsellors . Effects were first analysed among those participating in the baseline and post-intervention surveys and then as intention-to-treat analysis . The study was registered with www.controlled-trials.com , number IS RCT N53353725 . A total of 836 and 858 adults were assigned to the intervention and control clusters , respectively . In the intervention arm , counselling was accepted by 85 % and 66 % were tested ( n = 686 ) . Among counselled respondents who were cohabiting with the partner , 62 % were counselled together with the partner . At follow-up eight months later , the proportion of adults reporting to have been tested the year prior to follow-up was 82 % in the intervention arm and 52 % in the control arm ( Relative Risk ( RR ) 1.6 , 95 % CI 1.4 - 1.8 ) , whereas the RR was 1.7 ( 1.4 - 2.0 ) according to the intention-to-treat analysis . At baseline the likelihood of being tested was higher for women vs. men and for more educated people . At follow-up these differences were found only in the control communities . Measured negative life events following HIV testing were similar in both groups . In conclusion , this HB-VCT model was found to be feasible , with a very high acceptance and to have important equity effects . The high couple counselling acceptance suggests that the home-based approach has a particularly high HIV prevention potential The objective of this study is to describe HIV-testing among men in rural Lusaka Province , Zambia , using a population -based survey for a cluster-r and omized trial . Households ( N = 120 ) were r and omly selected from each of the 42 clusters , defined as a health facility catchment area . Individuals aged 15–60 years were invited to complete question naires regarding demographics and HIV-testing history . Men testing in the last year were defined as recent-testers . After question naire completion adults were offered home-based rapid HIV-testing . Of the 2,828 Output:	The results indicated that higher education was a common facilitator of HIV testing , while misconception of HIV testing and the fear of negative consequences were the major barriers for using the testing services . Other factors , such as demographic characteristics , marital dynamics , partner relationship , and relationship with the health care services , also greatly affects the participants ' decision making .
MS212024	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Patient reported outcomes ( PROs ) are especially useful in assessing treatments for rheumatoid arthritis ( RA ) since they measure dimensions of health-related quality of life that can not be captured using strictly objective physiological measures . The aim of this study was to compare the effects of combination etanercept and methotrexate ( ETN + MTX ) versus combination synthetic disease modifying antirheumatic drugs ( DMARDs ) and methotrexate ( DMARD + MTX ) on PRO measures among RA patients from the Asia-Pacific region , a population not widely studied to date . Patients with established moderate to severe rheumatoid arthritis who had an inadequate response to methotrexate were studied . Methods Patients were r and omized to either ETN + MTX ( N = 197 ) or DMARD + MTX ( N = 103 ) in an open-label , active-comparator , multicenter study , with PRO measures design ed as prospect i ve secondary endpoints . The Health Assessment Question naire ( HAQ ) , Functional Assessment of Chronic Illness Therapy Fatigue Scale ( FACIT-Fatigue ) , Medical Outcomes Short Form-36 Health Survey ( SF-36 ) , Hospital Anxiety and Depression Scale ( HADS ) and the Work Productivity and Activity Impairment Question naire : General Health ( WPAI : GH ) were used . Results Significantly greater improvements were noted for the ETN + MTX group at week16 for HAQ mean scores and for proportion of patients achieving HAQ score ≤ 0.5 , compared to patients in the DMARD + MTX group . SF-36 Summary Scores for physical and mental components and for 6 of 8 health domains showed significantly greater improvements at week16 for the ETN + MTX group ; only scores for physical functioning and role-emotional domains did not differ significantly between the two treatment arms . Greater improvements at week16 were noted for the ETN + MTX group for FACIT-Fatigue , HADS , and WPAI : GH mean scores . Conclusion Combination therapy using ETN + MTX demonstrated superior improvements using a comprehensive set of PRO measures , compared to combination therapy with usual st and ard of care DMARDs plus MTX in patients with established rheumatoid arthritis from the Asia-Pacific region . Trial registration clintrials.gov # AIM To study the effect of infliximab on fatigue in relation to cytokine levels in Crohn 's disease ( CD ) patients . METHODS Fourteen CD patients were blinded for treatment and received placebo at baseline , and infliximab 2 wk later , with a follow-up of 4 wk . Blood sample s were drawn on a regular basis , and question naires on fatigue , depression , quality of life , and clinical disease activity were completed at regular intervals . RESULTS After placebo infusion , fatigue scores decreased within 3 d ( 3.5 points + /- 1.1 , P < or= 0.01 ) , but returned to baseline values 14 d after this infusion . The drop of fatigue scores following infliximab infusion sustained until the end of the study ( 3.8 points + /- 1.4 , P < or= 0.05 ) . Quality of life was increased at the end of the study compared to baseline values ( 138.6 + /- 9.4 vs 179.4 + /- 6.7 ; P < or= 0.005 ) , whereas depression scores were decreased ( 20.4 + /- 9.4 vs 11.3 + /- 2.2 ; P < or= 0.01 ) . No correlation between the severity of fatigue and the level of cytokines was observed . CONCLUSION The reduction of fatigue after infliximab infusion is subjective to a placebo effect . The effect of infliximab on fatigue , however , persists while the placebo effect disappears after a short period of time . A clear role of cytokines could not be substantiated BACKGROUND Infectious , autoimmune , and neurodegenerative diseases are associated with profound psychological disturbances . Studies in animals clearly demonstrate that cytokines mediate illness-associated behavioral changes . However , the mechanisms underlying the respective psychological alterations in humans have not been established yet . Therefore , we investigated the effects of low-dose endotoxemia , a well-established and safe model of host-defense activation , on emotional , cognitive , immunological , and endocrine parameters . METHODS In a double-blind , crossover study , 20 healthy male volunteers completed psychological question naires and neuropsychological tests 1 , 3 , and 9 hours after intravenous injection of Salmonella abortus equi endotoxin ( 0.8 ng/kg ) or saline in 2 experimental sessions . Blood sample s were collected hourly , and rectal temperature and heart rate were monitored continuously . RESULTS Endotoxin had no effects on physical sickness symptoms , blood pressure , or heart rate . Endotoxin caused a mild increase in rectal temperature ( 0.5 degrees C ) , and increased the circulating levels of tumor necrosis factor alpha ( TNF-alpha ) , soluble TNF receptors , interleukin (IL)-6 , IL-1 receptor antagonist , and cortisol . After endotoxin administration , the subjects showed a transient significant increase in the levels of anxiety ( effect size [ ES ] = 0.55 ) and depressed mood ( ES = 0.66 ) . Verbal and nonverbal memory functions were significantly decreased ( ES = 0.55 to 0.64 ) . Significant positive correlations were found between cytokine secretion and endotoxin-induced anxiety ( r = 0.49 to r = 0.60 ) , depressed mood ( r = 0.40 to r = 0.75 ) , and decreases in memory performance ( r = 0.46 to r = 0.68 ) . CONCLUSIONS In humans , a mild stimulation of the primary host defense has negative effects on emotional and memory functions , which are probably caused by cytokine release . Hence , cytokines represent a novel target for neuropsychopharmacological research OBJECTIVE To identify factors predicting response to first TNF blocking treatment course in patients with established RA with a special focus on gender differences . METHODS Patients with active RA initiating their first treatment course of TNF-blocking therapy were enrolled . The study period was March 1999 through September 2006 . The prospect i ve protocol included information on demographics , clinical characteristics of patients and response measures . Fulfilment of ACR 50 - 70 % improvement and European League Against Rheumatism ( EULAR ) good response or remission [ 28-joint disease activity score ( DAS28 ) < 2.6 ] at 3 months were chosen as primary outcome measures . Potential predictors of responses were identified using multivariate binary logistic regression models . RESULTS In total , 1565 patients were included in the study . Gender did not influence treatment response . Consistently , concomitant methotrexate ( MTX ) was significantly associated with EULAR remission , EULAR good response , ACR50 response and ACR70 response with odds ratios ( ORs ) 1.97 , 2.13 , 2.10 and 1.75 , respectively . Concurrent treatment with other DMARDs was also significantly associated with EULAR remission , EULAR good response and ACR50 response ( OR : 1.96 , 2.24 and 1.94 , respectively ) . Likewise , low HAQ at baseline consistently predicted good clinical outcome . Disease activity at baseline was directly associated with favourable response when measured by ACR50 and ACR70 ( OR : 1.59 and 1.60 , respectively ) , whereas DAS28 score at baseline was inversely associated with EULAR remission ( OR : 0.78 ) . CONCLUSIONS In this observational study of patients with established RA , gender did not predict response to anti-TNF therapy , whereas treatment with concomitant DMARDs , especially MTX and low disability were associated with good response . Choice of outcome measures may influence the predictive value of baseline features Fatigue is a significant symptom in multiple sclerosis ( MS ) patients . First-generation disease modifying therapies ( DMTs ) are at best moderately effective to improve fatigue . Observations from small cohorts have indicated that natalizumab , an antibody targeting VLA-4 , may reduce MS-related fatigue . The TYNERGY study aim ed to further evaluate the effects of natalizumab treatment on MS-related fatigue . In this one-armed clinical trial including 195 MS patients , natalizumab was prescribed in a real-life setting , and a vali date d question naire , the Fatigue Scale for Motor and Cognitive functions ( FSMC ) , was used both before and after 12 months of treatment to evaluate a possible change in the fatigue experienced by the patients . In the treated cohort all measured variables , that is , fatigue score , quality of life , sleepiness , depression , cognition , and disability progression were improved from baseline ( all p values<0.0001 ) . Walking speed as measured by the six-minute walk-test also increased at month 12 ( p = 0.0016 ) . All patients were aware of the nature of the treatment agent , and of the study outcomes . Conclusion Natalizumab , as used in a real-life setting , might improve MS-related fatigue based on the results from this one-armed un-controlled stud . Also other parameters related to patients ' quality of life seemed to improve with natalizumab treatment . Trial Registration Clinical Trials.gov CONTEXT Increased concentrations of inflammatory biomarkers predict antidepressant nonresponse , and inflammatory cytokines can sabotage and circumvent the mechanisms of action of conventional antidepressants . OBJECTIVES To determine whether inhibition of the inflammatory cytokine tumor necrosis factor ( TNF ) reduces depressive symptoms in patients with treatment-resistant depression and whether an increase in baseline plasma inflammatory biomarkers , including high-sensitivity C-reactive protein ( hs-CRP ) , TNF , and its soluble receptors , predicts treatment response . DESIGN Double-blind , placebo-controlled , r and omized clinical trial . SETTING Outpatient infusion center at Emory University in Atlanta , Georgia . PARTICIPANTS A total of 60 medically stable out patients with major depression who were either on a consistent antidepressant regimen ( n = 37 ) or medication-free ( n = 23 ) for 4 weeks or more and who were moderately resistant to treatment as determined by the Massachusetts General Hospital Staging method . INTERVENTIONS Three infusions of the TNF antagonist infliximab ( 5 mg/kg ) ( n = 30 ) or placebo ( n = 30 ) at baseline and weeks 2 and 6 of a 12-week trial . MAIN OUTCOME MEASURES The 17-item Hamilton Scale for Depression ( HAM-D ) scores . RESULTS No overall difference in change of HAM-D scores between treatment groups across time was found . However , there was a significant interaction between treatment , time , and log baseline hs-CRP concentration ( P = .01 ) , with change in HAM-D scores ( baseline to week 12 ) favoring infliximab-treated patients at a baseline hs-CRP concentration greater than 5 mg/L and favoring placebo-treated patients at a baseline hs-CRP concentration of 5 mg/L or less . Exploratory analyses focusing on patients with a baseline hs-CRP concentration greater than 5 mg/L revealed a treatment response ( ≥50 % reduction in HAM-D score at any point during treatment ) of 62 % ( 8 of 13 patients ) in infliximab-treated patients vs 33 % ( 3 of 9 patients ) in placebo-treated patients ( P = .19 ) . Baseline concentrations of TNF and its soluble receptors were significantly higher in infliximab-treated responders vs nonresponders ( P < .05 ) , and infliximab-treated responders exhibited significantly greater decreases in hs-CRP from baseline to week 12 compared with placebo-treated responders ( P < .01 ) . Dropouts and adverse events were limited and did not differ between groups . CONCLUSIONS This proof-of-concept study suggests that TNF antagonism does not have generalized efficacy in treatment-resistant depression but may improve depressive symptoms in patients with high baseline inflammatory biomarkers . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00463580 Background Inflammatory cytokines are implicated in the pathophysiology of depression . In rodents , systemically administered inflammatory cytokines induce depression-like behavior . Similarly in humans , therapeutic interferon-α induces clinical depression in a third of patients . Conversely , patients with depression also show elevated pro-inflammatory cytokines . Objectives To determine the neural mechanisms underlying inflammation-associated mood change and modulatory effects on circuits involved in mood homeostasis and affective processing . Methods In a double-blind , r and omized crossover study , 16 healthy male volunteers received typhoid vaccination or saline ( placebo ) injection in two experimental sessions . Mood question naires were completed at baseline and at 2 and 3 hours . Two hours after injection , participants performed an implicit emotional face perception task during functional magnetic resonance imaging . Analyses focused on neurobiological correlates of inflammation-associated mood change and affective processing within regions responsive to emotional expressions and implicated in the etiology of depression . Results Typhoid but not placebo injection produced an inflammatory response indexed by increased circulating interleukin-6 and significant mood reduction at Output:	Adalimumab , etanercept , infliximab and tocilizumab all showed statistically significant improvements in depressive symptoms . Meta-regression exploring predictors of response found that the antidepressant effect was associated with baseline symptom severity ( P=0.018 ) but not with improvement in primary physical illness , sex , age or study duration . The findings indicate a potentially causal role for cytokines in depression and that cytokine modulators may be novel drugs for depression in chronically inflamed subjects .
MS212025	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND --Tuberculous pleurisy can result in pleural fibrosis , calcification and thickening . To prevent these complications , corticosteroids are frequently used in addition to antituberculous drugs ; however , new therapeutic regimens can control the disease and minimise the sequelae , and there is no convincing evidence of the benefit of the use of corticosteroids as adjuvant therapy . METHODS -- Patients received isoniazid 5 mg/kg and rifampicin 10 mg/kg daily for six months . Additionally , they were r and omly assigned to a double blind treatment with either prednisone ( 1 mg/kg/day for 15 days and then tapering off ) or placebo during the first month of treatment . Different clinical , radiological , and functional parameters were evaluated to assess the effect of corticosteroids . RESULTS --Fifty seven patients received prednisone and 60 placebo . At the end of the treatment the clinical outcome , the rate of reabsorption of the pleural fluid , the pleural sequelae , as well as lung capacity were similar in both groups . CONCLUSIONS --Corticosteroids do not influence the clinical outcome or the development of long term pleural sequelae in tuberculous pleurisy To determine the effect of adjunct therapy , we carried out a prospect i ve cohort study on 190 patients with tuberculous pleural effusion during May 2003-April 2004 . Patients were divided into 3 groups . All groups were treated with anti-tuberculosis ( TB ) drugs for 6 months ; in group 2 ( n = 46 ) prednisolone , 30 mg/day for 10 days , was added ; group 3 ( n = 78 ) were given paracentesis to remove fluid . Fever and constitutional symptoms disappeared faster in group 2 ( P > 0.05 ) . After 10 days , there was a significantly greater reduction in the size of pleural effusion in group 2 , but after 6 months the difference was not statistically significant . We found corticosteroids and therapeutic paracentesis are not necessary in the management of TB pleural effusion BACKGROUND Active tuberculosis may accelerate progression of human immunodeficiency virus ( HIV ) infection by promoting viral replication in activated lymphocytes . Glucocorticoids are used in pleural tuberculosis to reduce inflammation-induced pathology , and their use also might reduce progression of HIV by suppressing immune activation . We examined the effect that prednisolone has on survival in HIV-1-associated pleural tuberculosis . METHODS We conducted a r and omized , double-blind , placebo-controlled trial of prednisolone as an adjunct to tuberculosis treatment , in adults with HIV-1-associated pleural tuberculosis . The primary outcome was death . Analysis was by intention to treat . RESULTS Of 197 participants , 99 were assigned to the prednisolone group and 98 to the placebo group . The mortality rate was 21 deaths/100 person-years ( pyr ) in the prednisolone group and 25 deaths/100 pyr in the placebo group ( age- , sex- , and initial CD4 + T cell count-adjusted mortality rate ratio , 0.99 [ 95 % confidence interval , 0.62 - 1.56 ] [ P = .95 ] ) . Resolution of tuberculosis was faster in the prednisolone group , but recurrence rates were slightly ( though not significantly ) higher , and use of prednisolone was associated with a significantly higher incidence of Kaposi sarcoma ( 4.2 cases/100 pyr , compared with 0 cases/100 pyr [ P = .02 ] ) . CONCLUSIONS In view of the lack of survival benefit and the increased risk of Kaposi sarcoma , the use of prednisolone in HIV-associated tuberculous pleurisy is not recommended Although several studies on tuberculous ( TB ) pleurisy suggest that the addition of corticosteroids to anti-TB therapy may have beneficial effects , these agents are not used routinely . To assess the effects of short-term oral prednisone therapy in TB pleurisy , 74 patients were r and omly assigned in a double-blind fashion to treatment with either placebo or prednisone at a dose of 0.75 mg/kg/d for up to 4 weeks with gradual reduction over an additional 2 weeks . All subjects received a st and ard 3-drug anti-TB chemotherapy regimen for 6 months . TB pleurisy was diagnosed by histologic study and /or culture of pleural biopsy specimens obtained at thoracoscopy . Complete drainage of the effusion was performed simultaneously . Outcome measures were assessed periodically for 24 weeks , including indexes of morbidity and pleural thickening . After r and omization , four patients were excluded from the final analysis . Of the 70 patients analyzed , 34 received prednisone and 36 received placebo . Demographic and clinical characteristics of the treatment groups were comparable at the time of hospital admission . Although a statistically significant improvement in symptoms occurred earlier in the prednisone group ( 8 weeks ) than in the placebo group ( 12 weeks ) , between-group comparison showed no significant differences at any of the follow-up evaluations . The proportion of subjects in the prednisone group ( 53.1 % ) with residual pleural thickening at 6 months did not differ significantly from that of the placebo group ( 60 % ) . Pleural effusions did not recur in any of the patients . Initial complete drainage of the effusion was associated with greater symptomatic improvement than any subsequent therapy . We conclude that st and ard anti-TB therapy and early complete drainage is adequate for the treatment of TB pleurisy . The addition of short-term oral prednisone therapy neither results in clinical ly relevant earlier symptom relief nor confers a beneficial effect on residual pleural thickening Output:	Compared to the controls ( placebos or non-steroids ) , adjunctive corticosteroid use reduced the risk of residual pleural fluid after 4 weeks and the number of days to symptom improvement ; however , there was no convincing evidence to support the positive effects of corticosteroids over the long term ( 8 weeks ) on residual pleural fluid , pleural thickening , or pleural adhesions , and there was no statistical difference between the corticosteroid group and control group with respect to 7-days relief of the clinical symptoms or death from any cause . In addition , more adverse events were observed in patients who received corticosteroids than in those in the control group . Our results suggest that adjunctive corticosteroid use did not improve long-term efficacy and might induce more adverse events , although the risk of residual pleural fluid at 4 weeks and the number of days to symptom improvement were reduced
MS212026	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background The objective of this r and omized prospect i ve study was to compare the efficacy of 50 mcg vaginal misoprostol and 3 mg dinoprostone , administered every nine hours for a maximum of three doses , for elective induction of labor in a specific cohort of nulliparous women with an unfavorable cervix and more than 40 weeks of gestation . Material and Methods One hundred and sixty-three pregnant women with more than 285 days of gestation were recruited and analyzed . The main outcome measures were time from induction to delivery and incidence of vaginal delivery within 12 and 24 hours . Admission rate to the neonatal intensive care unit within 24 hours post delivery was a secondary outcome . Results The induction-delivery interval was significantly lower in the misoprostol group than in the dinoprostone group ( 11.9 h vs. 15.5 h , p < 0.001 ) . With misoprostol , more women delivered within 12 hours ( 57.5 % vs. 32.5 % , p < 0.01 ) and 24 hours ( 98.7 % vs. 91.4 % , p < 0.05 ) , spontaneous rupture of the membranes occurred more frequently ( 38.8 % vs. 20.5 % , p < 0.05 ) , there was less need for oxytocin augmentation ( 65.8 % vs. 81.5 % , p < 0.05 ) and fewer additional doses were required ( 7.5 % vs. 22 % , p < 0.05 ) . Although not statistically significant , a lower Caesarean section ( CS ) rate was observed with misoprostol ( 7.5 % vs. 13.3 % , p > 0.05 ) but with the disadvantage of higher abnormal fetal heart rate ( FHR ) tracings ( 22.5 % vs. 12 % , p > 0.05 ) . From the misoprostol group more neonates were admitted to the intensive neonatal unit , than from the dinoprostone group ( 13.5 % vs. 4.8 % , p > 0.05 ) . One woman had an unexplained stillbirth following the administration of one dose of dinoprostone . Conclusions Vaginal misoprostol , compared with dinoprostone in the regimens used , is more effective in elective inductions of labor beyond 40 weeks of gestation . Nevertheless , this is at the expense of more abnormal FHR tracings and more admissions to the neonatal unit , indicating that the faster approach is not necessarily the better approach to childbirth Objective To compare vaginal misoprostol with dinoprostone for induction of labour Summary : A prospect i ve r and omised controlled trial was performed to compare the efficacy and safety of intrav‐aginal misoprostol to that of intravaginal dinoprostone when used for cervical priming prior to the induction of labour ; 126 women were recruited to the study and r and omised to receive either intravaginal dinoprostone ( n = 63 ) or misoprostol ( n = 63 ) for cervical priming prior to induction of labour . The mean time from insertion of the priming agent to vaginal delivery was significantly shorter in the misoprostol group ( 925.8 versus 1577.6 minutes ) , the mean duration of the active length of labour was significantly shorter in the misoprostol group ( 353.7 versus 496.8 minutes ) and more women in the misoprostol group delivered in less than 12 hours ( 92 % versus 76.5 % ) The objective of this study was to determine the safety of obstetrics forceps when used under strictly defined criteria compared to vacuum extraction for delivery in the second stage of labour . A r and omised prospect i ve trial was performed on 442 women undergoing instrumental delivery in the second stage . Two hundred and four women were in the forceps group and 238 in the vacuum group . When using forceps traction efforts to deliver the baby were kept to less than three and the head was always delivered in the occipito-anterior position . In the two groups there were no significant difference in the incidence of third-degree perineal tears , post-partum haemorrhage or ruptured uterus . Cervical tears were slightly higher in the forceps group . Babies delivered by vacuum extraction showed a higher incidence of cephalhaematomas . There was no significant difference in babies needing resuscitation at birth , admission to neonatal intensive care unit , stillbirth or neonatal death rates . The failure rate was significantly higher in the vacuum group . The time taken to complete the procedure was significantly less in the forceps group . Forceps deliveries when performed under defined criteria are as safe as vacuum deliveries to the mother with a lesser failure rate and a lower incidence of cephalhaematomas in the neonate compared with vacuum deliveries OBJECTIVE To compare the effectiveness of vaginally administered misoprostol with extra-amniotic prostagl and in F2alpha ( PGF2alpha ) gel for induction of labor . METHOD A r and omized controlled trial , with women allocated to receive either misoprostol 50 microg intra-vaginally or extra-amniotic PGF2alpha gel 5 mg , was conducted in Harare Maternity Hospital . A total of 152 women were admitted for induction of labor with a term singleton , pregnancy and cephalic presentation were recruited . The main outcome was duration of induction . RESULTS There were no differences in the characteristics of women in the two groups at recruitment . In the misoprostol group there was a significantly reduced need for augmentation of labor with oxytocin ( OR=0.36 ; 95 % C.I. 0.17 - 0.73 ) and delivery by cesarean section for failure to progress ( OR=0.11 ; 95 % C.I. 0.00 - 0.88 ) . The risk for duration of induction to vaginal delivery exceeding 12 , 18 or 24 h was reduced by 18 % , 38 % and 68 % , respectively , but only the risk for duration > 24 h was significantly reduced ( OR=0.32 ; 95%C.I. 0.11 - 0.91 ) . The mean duration of induction was shorter in the misoprostol group , 15.2 vs. 23.6 h ( P=0.02 ) . There were no differences in fetal outcome . CONCLUSION Misoprostol 50 microg was associated with less use of oxytocin in labor , a shorter induction to delivery interval and fewer cesarean sections for failure to progress when compared with extra-amniotic PGF2alpha gel BACKGROUND The aims of the present study were to determine whether maternal hyperoxygenation affects human fetal pulmonary circulation and whether there is a gestational age-related response in the fetal pulmonary circulation to maternal hyperoxygenation during the second half of gestation . METHODS AND RESULTS Twenty women between 20 and 26 weeks of gestation and 20 women between 31 and 36 weeks of gestation with normal singleton pregnancies were r and omized to receive either 60 % humidified oxygen or medical compressed air ( room air ) by a face mask . Fetal aortic and pulmonary valve ; ductus arteriosus ( DA ) ; and right ( RPA ) , left ( LPA ) , and distal ( DPA ) pulmonary artery blood velocity waveforms were obtained by Doppler ultrasound before , during , and after maternal administration of either 60 % oxygen or room air . Left and right ventricular cardiac outputs , DA volume blood flow , and RPA and LPA volume blood flows ( Qp ) were calculated . Foramen ovale volume blood flow ( left ventricular cardiac output-Qp ) was estimated . Pulsatility index ( PI ) values of DA , RPA , LPA , and DPA were calculated . Maternal hyperoxygenation did not change any of the measured fetal parameters between 20 and 26 weeks , whereas between 31 and 36 weeks , the PI values of RPA , LPA , and DPA decreased ( P<.0001 ) and the PI of DA increased ( P<.0001 ) . In addition , Qp increased ( P<.001 ) , and DA volume blood flow ( P<.01 ) and foramen ovale volume blood flow ( P<.03 ) decreased . Left and right ventricular cardiac outputs were unchanged . All changes returned to baseline after maternal hyperoxygenation was discontinued . CONCLUSIONS Reactivity of the human fetal pulmonary circulation to maternal hyperoxygenation increases with advancing gestation ; this suggests that fetal pulmonary circulation is under acquired vasoconstriction at least after 31 to 36 weeks of gestation Background Improving maternal health by reducing maternal mortality constitutes the fifth Millennium Development Goal and represents a key public health challenge in the United Republic of Tanzania . In response to the need to evaluate and monitor safe motherhood interventions , this study aims at assessing the coverage of obstetric care according to the Unmet Obstetric Need ( UON ) concept by obtaining information on indications for , and outcomes of , major obstetric interventions . Furthermore , we explore whether this concept can be operationalised at district level . Methods A two year study using the Unmet Obstetric Need concept was carried out in three districts in Tanga Region , Tanzania . Data was collected prospect ively at all four hospitals in the region for every woman undergoing a major obstetric intervention , including indication and outcome . The concept was adapted to address differentials in access to emergency obstetric care between districts and between rural and urban areas . Based upon literature and expert consensus , a threshold of 2 % of all deliveries was used to define the expected minimum requirement of major obstetric interventions performed for absolute maternal indications . Results Protocol s covering 1,260 complicated deliveries were analysed . The percentage of major obstetric interventions carried out in response to an absolute maternal indication was only 71 % ; most major obstetric interventions ( 97 % ) were caesarean sections . The most frequent indication was cephalo-pelvic-disproportion ( 51 % ) . The proportion of major obstetric interventions for absolute maternal indications performed amongst women living in urban areas was 1.8 % of all deliveries , while in rural areas it was only 0.7 % . The high proportion ( 8.3 % ) of negative maternal outcomes in terms of morbidity and mortality , as well as the high perinatal mortality of 9.1 % ( still birth 6.9 % , dying within 24 hours 1.7 % , dying after 24 hours 0.5 % ) raise concern about the quality of care being provided . Conclusion Based on the 2 % threshold , Tanga Region – with an overall level of major obstetric interventions for absolute maternal indications of 1 % and a caesarean section rate of 1.4 % – has significant unmet obstetric need with a considerable rural-urban disparity . The UON concept was found to be a suitable tool for evaluating and monitoring the coverage of obstetric care at district level Objective To investigate the effect of chronic oxygen therapy in fetuses with absent end diastolic flow in the umbilical artery assessed by doppler analysis at 24–30 weeks of gestation OBJECTIVE Our purpose was to determine the optimal management of pregnancies beyond 41 week 's gestation with a cervix unfavorable for induction . MATERIAL AND METHOD All uncomplicated pregnancies that reached 41 weeks'gestation with a Bishop score of < or = 4 , were r and omly assigned to one of two groups RESULTS The duration of labor was shorter in the group " prépidil " compared with the control group ( P=0.002 ) . Identification of an unfavorable cervix at 41 weeks was unlikely to change by 42 weeks and cervical ripening was required in 40 % cases . There was no significant difference in caesarean section rates . Rates of admission into the neonatal unit and fetal outcomes were similar in the two groups . CONCLUSION Cervical ripening with prostagl and in gel at 41 week 's gestation for uncomplicated singleton pregnancies is safe and should be advocated BACKGROUND Research suggests that fetal exposure to magnesium sulfate before preterm birth might reduce the risk of cerebral palsy . METHODS In this multicenter , placebo-controlled , double-blind trial , we r and omly assigned women at imminent risk for delivery between 24 and 31 weeks of gestation to receive magnesium sulfate , administered intravenously as a 6-g bolus followed by a constant infusion of 2 g per hour , or matching placebo . The primary outcome was the composite of stillbirth or infant death by 1 year of corrected age or moderate or severe cerebral palsy at or beyond 2 years of corrected age . RESULTS A total of 2241 women underwent r and omization . The baseline characteristics were similar in the two groups . Follow-up was achieved for 95.6 % of the children . The rate of the primary outcome was not significantly different in the magnesium sulfate group and the placebo group ( 11.3 % and 11.7 % , respectively ; relative risk , 0.97 ; 95 % confidence interval [ CI ] , 0.77 to 1.23 ) . However , in a prespecified secondary analysis , moderate or severe cerebral palsy occurred significantly less frequently in the magnesium sulfate group ( 1.9 % vs. 3.5 % ; relative risk , 0.55 ; 95 % CI , 0.32 to 0.95 ) . The risk of death did not differ significantly between the groups ( 9.5 % vs. 8.5 % ; relative risk , 1.12 ; 95 % CI , 0.85 to 1.47 ) . No woman had a life-threatening event . CONCLUSIONS Fetal exposure to magnesium sulfate before anticipated early preterm delivery did not reduce the Output:	Results We found a paucity of studies reporting statistically significant evidence of impact on perinatal mortality , especially on stillbirths . Available evidence suggests that operative delivery , especially Caesarean section , contributes to decreased stillbirth rates . Induction of labour rather than expectant management in post-term pregnancies showed strong evidence of impact , though there was not enough evidence to suggest superior safety for the fetus of any given drug or drugs for induction of labour . Magnesium sulphate for pre-eclampsia and eclampsia is effective in preventing eclamptic seizures , but studies have not demonstrated impact on perinatal mortality . There was limited evidence of impact for maternal hyperoxygenation , and concerns remain about maternal safety . Transcervical amnioinfusion for meconium staining appears promising for low/middle income-country application according to the findings of many small studies , but a large r and omised trial of the intervention had no significant impact on perinatal mortality , suggesting that further studies are needed . Conclusion Although the global appeal to prioritise access to emergency obstetric care , especially vacuum extraction and Caesarean section , rests largely on observational and population -based data , these interventions are clearly life-saving in many cases of fetal compromise .
MS212027	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Colorectal cancer ( CRC ) screening is underutilized despite evidence that screening reduces mortality . OBJECTIVE To assess the effect of an intervention targeting physicians and their patients on rates of CRC screening . DESIGN A r and omized clinical trial of community physicians and their patients . PARTICIPANTS Ninety-four community primary care physicians r and omly assigned to an intervention consisting of academic detailing and direct mailings to patients or a control group . Patients aged 50 to 79 years in the intervention group physicians received a letter from their physician , a brochure on CRC screening , and a packet of fecal occult blood test ( FOBT ) cards . MEASUREMENTS After 1 year we measured receipt of the following : ( 1 ) FOBT in the past 2 years , ( 2 ) flexible sigmoidoscopy ( SIG ) or colonoscopy ( COL ) in the previous 5 years , and ( 3 ) any CRC screening . We report the percent change from baseline in both groups . RESULTS 9,652 patients were enrolled for 2 years , and 3,732 patients were enrolled for 5 years . There was no increase in any CRC screening that occurred in the intervention group for patients enrolled for 2 years ( 12.7 increase vs 12.5 % , P=.51 ) . Similar results were seen for any CRC screening among patients enrolled for 5 years ( 9.7 % increase vs 8.6 % , P=.45 ) . The only outcome on which the intervention had an effect was on patient rates of screening SIG ( 7.4 % increase vs 4.4 % , P<.01 ) . CONCLUSION With the exception of an increase in rates of SIG in the intervention group , the intervention had no effect on rates of CRC screening . Future interventions should assess innovative approaches to increase rates of CRC screening BACKGROUND Complete diagnostic evaluation or CDE ( i.e. , colonoscopy or combined flexible sigmoidoscopy plus barium enema X-ray ) is often not performed for persons with an abnormal screening fecal occult blood test ( FOBT+ ) result . METHOD This study evaluated the impact of a reminder-feedback and educational outreach intervention on primary care practice CDE recommendation and performance rates . Four hundred seventy primary care physicians ( PCPs ) in 318 practice s participated in the study . Patients were mailed an FOBT kit annually as part of a screening program . Practice s were r and omly assigned to a Control Group ( N = 198 ) or an Intervention Group ( N = 120 ) . During an 18-month pre-r and omization period and a 9-month post-r and omization period , 2992 screening FOBT+ patients were identified . Intervention practice s received the screening program and the intervention . Control practice s received only the screening program . Study outcomes were baseline-adjusted CDE recommendation and performance rates . RESULTS At baseline , about two-thirds of FOBT+ patients received a CDE recommendation , and about half had a CDE performed . At endpoint , CDE recommendation and performance rates were both significantly higher for the Intervention as compared to the Control practice s ( OR = 2.28 ; 95 % CI : 1.37 , 3.78 , and OR = 1.63 ; 95 % CI : 1.06 , 2.50 , respectively ) . CONCLUSIONS The reminder-feedback plus educational outreach intervention significantly increased CDE recommendation and performance BACKGROUND To promote prevention and early detection of cancer , the authors conducted a three-year intervention targeting Vietnamese physicians in solo practice in California . METHODS Twenty subjects who had received their medical training in Vietnam were recruited into a r and omized controlled trial . The intervention included computerized or manual cancer screening reminders , continuing medical education seminars , Vietnamese- language health education material s , newsletters , and oncology data -query programs . Evaluation included chart audits for eight targeted activities pre- and post-intervention . RESULTS Before the intervention , annual physician performance rates were low for all eight activities : routine checkups ( 65.6 % ) , Pap testing ( 13.8 % ) , pelvic examinations ( 19.8 % ) , clinical breast examinations ( 13.3 % ) , mammography ( 6.4 % ) , hepatitis B serologies ( 21.9 % ) , hepatitis B immunizations ( 12.8 % ) , and smoking cessation counseling ( 1.6 % ) . After the intervention , performance rates increased significantly for smoking cessation counseling ( p = 0.02 ) , Pap testing ( p = 0.004 ) , and pelvic examinations ( p = 0.01 ) . CONCLUSIONS The results demonstrate the efficacy of an intervention targeting Vietnamese primary care physicians in promoting smoking cessation counseling , Pap testing , and pelvic examinations , but not other cancer prevention activities A multifaceted , individualized , physician education program design ed to increase the breast cancer screening practice s of community-based primary care physicians is described and the results are evaluated . Community-based surveys identified primary care providers with breast cancer screening educational needs who were assigned , using a factorial design , to an intervention or control condition . The sample included 154 control and 128 intervention physicians . The intervention consisted of a 1 - 2h in-office training program and /or self- study workbook . Self-reported overall breast cancer screening need scores improved for a greater proportion of intervention than control physicians , particularly those receiving the in-office intervention ( P=0.03 ) . Clinical breast examination ( CBE ) need declined ( P=0.01 ) ; use of provider reminder systems increased ( P=0.02 ) ; preparedness to counsel about CBE ( P=0.04 ) and recognition that age is an important risk factor for breast cancer ( P=0.02 ) improved in more intervention compared to control physicians BACKGROUND Urban minority groups , such as those living in northern Manhattan and the South Bronx , are generally underserved with regard to breast cancer prevention and screening practice s. Primary care physicians are critical for the recommendation of mammography and clinical breast examinations to their patients . DESIGN Two medically underserved communities were matched and block r and omized . The aim of the study was to assess the efficacy of academic detailing in increasing recommendations for breast cancer screening in community-based primary care physicians . SETTING / PARTICIPANTS Ninety-four primary care community-based ( ie , not hospital-based ) physicians in northern Manhattan were compared with 74 physicians in the South Bronx who received no intervention . INTERVENTION INTERVENTION participants received multicomponent physician-directed education , academic detailing , using the American Cancer Society guidelines for the early detection of breast cancer . MAIN OUTCOME MEASURES We administered interviews to ask about primary care physicians ' recommendation of mammography and clinical breast examination . They were also queried about their knowledge of major risk factors and perceived barriers to breast cancer screening . We conducted medical audits of 710 medical charts 2 years before and after the intervention . RESULTS Using a mixed models linear analysis , we found a statistically significant intervention effect on the recommendation of mammography and clinical breast examination ( according to medical audit ) by female patients age 40 and over . INTERVENTION group physicians correctly identified significantly more risk factors for breast cancer , and significantly fewer barriers to practice , than did comparison physicians . CONCLUSIONS We found some evidence of improvement in breast cancer screening practice s due to academic detailing among primary care physicians practicing in urban underserved communities BACKGROUND Very little effort has been directed to enable GPs to better informed decisions about PSA screening among their male patients . OBJECTIVES To evaluate an innovative programme design ed to enhance GPs ' capacity to promote informed decision making by male patients about PSA screening . METHODS The study design was a cluster r and omised controlled trial set in New South Wales , Australia 's most populous state . 277 GPs were recruited through a major pathology laboratory . The interventions were three telephone-administered ' peer coaching ' sessions integrated with educational re sources for GPs and patients and the main outcome measures were : GP knowledge ; perceptions of patient involvement in informed decision making ; GPs ' own decisional conflict ; and perceptions of medicolegal risk . RESULTS Compared with GPs allocated to the control group , GPs allocated to our intervention gained significantly greater knowledge about PSA screening and related information [ Mean 6.1 out of 7 ; 95 % confidence interval ( CI ) = 5.9 - 6.3 versus 4.8 ; 95 % CI = 4.6 - 5.0 ; P < 0.001 ] . They were less likely to agree that patients should remain passive when making decisions about PSA screening [ Odds ratio ( OR ) = 0.11 ; 95 % CI = 0.04 - 0.31 ; P < 0.001 ] . They perceived less medicolegal risk when not acceding to an ' uninformed ' patient request for a PSA test ( OR = 0.31 ; 95 % CI 0.19 - 0.51 ) . They also demonstrated lower levels of personal decisional conflict about the PSA screening ( Mean 25.4 ; 95 % CI 24.5 - 26.3 versus 27.8 ; 95 % CI 26.6 - 29.0 ; P = 0.0002 ) . CONCLUSION A ' peer coaching ' programme , supplemented by education material s , holds promise as a strategy to equip GPs to facilitate informed decision making amongst their patients BACKGROUND Screening reduces colorectal cancer mortality , but effective screening tests remain underused . Systematic reminders to patients and physicians could increase screening rates METHODS We conducted a r and omized controlled trial of patient and physician reminders in 11 ambulatory health care centers . Participants included 21 860 patients aged 50 to 80 years who were overdue for colorectal cancer screening and 110 primary care physicians . Patients were r and omly assigned to receive mailings containing an educational pamphlet , fecal occult blood test kit , and instructions for direct scheduling of flexible sigmoidoscopy or colonoscopy . Physicians were r and omly assigned to receive electronic reminders during office visits with patients overdue for screening . The primary outcome was receipt of fecal occult blood testing , flexible sigmoidoscopy , or colonoscopy over 15 months , and the secondary outcome was detection of colorectal adenomas . RESULTS Screening rates were higher for patients who received mailings compared with those who did not ( 44.0 % vs 38.1 % ; P < .001 ) . The effect increased with age : + 3.7 % for ages 50 to 59 years ; + 7.3 % for ages 60 to 69 years ; and + 10.1 % for ages 70 to 80 years ( P = .01 for trend ) . Screening rates were similar among patients of physicians receiving electronic reminders and the control group ( 41.9 % vs 40.2 % ; P = .47 ) . However , electronic reminders tended to increase screening rates among patients with 3 or more primary care visits ( 59.5 % vs 52.7 % ; P = .07 ) . Detection of adenomas tended to increase with patient mailings ( 5.7 % vs 5.2 % ; P = .10 ) and physician reminders ( 6.0 % vs 4.9 % ; P = .09 ) . CONCLUSIONS Mailed reminders to patients are an effective tool to promote colorectal cancer screening , and electronic reminders to physicians may increase screening among adults who have more frequent primary care visits Background Few patients with lower bowel symptoms who consult their general practitioner need a specialist opinion . However data from referred patients suggest that those who are referred would benefit from detailed assessment before referral . Methods A cluster r and omised factorial trial . 44 general practice s in North Trent , UK . Practice s were offered either an electronic interactive referral pro forma , an educational outreach visit by a local colorectal surgeon , both or neither . The main outcome measure was the proportion of cases with severe diverticular disease , cancer or precancerous lesions and inflammatory bowel disease in those referred by each group . A secondary outcome was a referral letter quality score . Semi-structured interviews were conducted to identify key themes relating to the use of the software Results From 150 invitations , 44 practice s were recruited with a total list size of 265,707 . There were 716 consecutive referrals recorded over a six-month period , for which a diagnosis was available for 514 . In the combined software arms 14 % ( 37/261 ) had significant pathology , compared with 19 % ( 49/253 ) in the non-software arms , relative risk 0.73 ( 95 % CI : 0.46 to 1.15 ) . In the combined educational outreach arms 15 % ( 38/258 ) had significant pathology compared with 19 % ( 48/256 ) in the non-educational arms , relative risk 0.79 ( 95 % CI : 0.50 to 1.24 ) . Pro forma practice s documented better assessment of patients at referral . Conclusion There was a lack of evidence that either intervention increased the proportion of patients with organic pathology among those referred . The interactive software did improve the amount of information relayed in referral letters although we were unable to confirm if this made a significant difference to patients or their health care providers . The potential value of either intervention may have been diminished by their limited uptake within the context of a cluster r and omised clinical trial . A number of lessons were learned in this trial of novel innovations BACKGROUND Colorectal cancer is the second leading cause of cancer mortality in israel . Unfortunately , compliance with annual fecal occult blood testing is very low . OBJECTIVE To assess the effectiveness Output:	RESULTS We found sufficient evidence that interactive education , computerised reminder systems and audit and feedback delivered to clinicians may significantly increase several cancer detection measures in the short term and some evidence that they promote early diagnosis . Whilst educational outreach and local opinion leaders had some effect , formal education alone seemed ineffectual . Certain educational interventions delivered at a clinician as well as at a practice level may promote the early diagnosis of cancer in primary care . There is currently limited evidence for their long-term sustainability and effectiveness
MS212028	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The efficacy of a communication skills training programme was shown through a r and omised trial . Oncologists ( N=160 ) from 34 cancer centres were allocated to written feedback plus course ; course alone ; written feedback alone or control . Each clinician had 6 – 10 interviews with patients videotaped at baseline and 3 months postintervention . Analysis of videotapes revealed improvements in the communication skills of clinicians r and omised to training ( n=80 ) compared with others ( n=80 ) . A 12-month follow-up assessment is reported here . Robust Poisson conditional analyses of counts of changes in communication behaviours revealed no demonstrable attrition in those who had shown improvement previously , including fewer leading questions , appropriate use of focused and open-ended questions and responses to patient cues . Additional skills , not apparent at 3 months , were now evident ; the estimated effect sizes corresponded to 81 % fewer interruptions ( P=0.001 ) and increased summarising of information to 38 % ( P=0.038 ) . However , expressions of empathy ( 54 % , P=0.001 ) declined . The overall results show that 12 – 15 months postintervention , clinicians had integrated key communication skills into clinical practice and were applying others . This is the first RCT to show an enduring effect of communication skills training with transfer into the clinic This study compared an activation intervention to passive education in a r and omized attention-control trial of 232 patients with type 2 diabetes . The activation intervention was based on Exp and ing Patient Involvement in Care ( EPIC ) trials , and was compared to time-matched passive education viewing of ADA video-tapes . Patient demographics and clinical characteristics of their diabetes were assessed with question naires , active involvement was assessed via ratings of taped interactions between patients and providers , and serum sample s were analyzed for HbA1c . Patients in the activation condition were rated as more actively involved in discussion s of diabetes self-management , and rated active involvement was predictive of improvement in glycemic control . No effect of the activation intervention was found on HbA1c . Thus , the activation intervention increased the active involvement of patients with type 2 diabetes in visits with practitioners , and active involvement led to improved glycemic control . However , the activation intervention did not improve glycemic control directly The authors assessed whether patient empowerment in the management of hypertension improved more with the practice of shared decision making ( SDM ) than by education programs . In a prospect i ve controlled clinical study , 15 general practitioners in Nuremberg , Germany who were specially trained to conduct SDM consultations participated in a 12-month study . Hypertensive patients ( N=86 ) were included ; N=40 were in the SDM group and N=46 were in the control group , if blood pressures were > or = 135 / 85 mm Hg ( self measurement ) and patients had no signs of cardiovascular complications or severe hypertension . All participants in the SDM group and the control group were enrolled in an education program on hypertension in small groups . The SDM group participants also had 4 special consultations to share medical decisions . The main outcome measures were the effect of SDM on blood pressure control . After 1 year blood pressure had decreased in all participants : Delta-9.26 + /- 10.2 mm Hg/Delta-5.33 + /- 9.5 mm Hg in the SDM group ( P<0.001 ) compared to Delta-6.0 + /- 11.8 mm Hg/Delta-3.0 + /- 8.3 mm Hg in the control group . There was no significant difference between the 2 groups . The study group practice d more SDM than controls , but blood pressure control was not significantly better . Patient empowerment by means of an education program in small groups and creating awareness of hypertensive disease helps to improve the outcome of hypertension treatment . SDM , however , did not improve management when compared to an education program , which is much easier to implement in general practice OBJECTIVE Despite the importance of self-management support ( SMS ) , few studies have compared SMS interventions , involved diverse population s , or entailed implementation in safety net setting s. We examined the effects of two SMS strategies across outcomes corresponding to the Chronic Care Model . RESEARCH DESIGN AND METHODS A total of 339 out patients with poorly controlled diabetes from county-run clinics were enrolled in a three-arm trial . Participants , more than half of whom spoke limited English , were uninsured , and /or had less than a high school education , were r and omly assigned to usual care , interactive weekly automated telephone self-management support with nurse follow-up ( ATSM ) , or monthly group medical visits with physician and health educator facilitation ( GMV ) . We measured 1-year changes in structure ( Patient Assessment of Chronic Illness Care [ PACIC ] ) , communication processes ( Interpersonal Processes of Care [ IPC ] ) , and outcomes ( behavioral , functional , and metabolic ) . RESULTS Compared with the usual care group , the ATSM and GMV groups showed improvements in PACIC , with effect sizes of 0.48 and 0.50 , respectively ( P < 0.01 ) . Only the ATSM group showed improvements in IPC ( effect sizes 0.40 vs. usual care and 0.25 vs. GMV , P < 0.05 ) . Both SMS arms showed improvements in self-management behavior versus the usual care arm ( P < 0.05 ) , with gains being greater for the ATSM group than for the GMV group ( effect size 0.27 , P = 0.02 ) . The ATSM group had fewer bed days per month than the usual care group ( −1.7 days , P = 0.05 ) and the GMV group ( −2.3 days , P < 0.01 ) and less interference with daily activities than the usual care group ( odds ratio 0.37 , P = 0.02 ) . We observed no differences in A1C change . CONCLUSIONS Patient-centered SMS improves certain aspects of diabetes care and positively influences self-management behavior . ATSM seems to be a more effective communication vehicle than GMV in improving behavior and quality of life OBJECTIVE To determine if a patient-centered , computer-assisted diabetes care intervention increased perceived autonomy support , perceived competence ( from self-determination theory ) , and if these constructs mediated the effect of the intervention on ADA/NCQA recommended diabetes care outcomes . DESIGN A r and omized controlled trial of 866 adult type 2 diabetes patients in heterogeneous primary care setting s in Colorado . MAIN OUTCOME MEASURES Perceived autonomy support , perceived competence , patient satisfaction , glycemic control ( HbA1c ) , ratio of total to HDL cholesterol , diabetes distress , and depressive symptoms . RESULTS The computer-assisted intervention increased patient perception of autonomy support relative to a computer-based control condition ( p = .05 ) . Change in perceived competence partially mediated the effects of increased autonomy support on the change in lipids , diabetes distress , and depressive symptoms . The construct of autonomy support was found to be separate from that of patient satisfaction . CONCLUSIONS A patient-centered , computer-assisted intervention was effective in improving diabetes self-management outcomes , in part , because it increased patients ' perception that their autonomy was supported which changed perceived competence . These findings support the self-determination model for health behavior change and the chronic care model and support the further study of the use of these technologies to motivate patients to improve their health outcomes OBJECTIVE To ascertain whether the quality of physician-patient communication makes a significant difference to patient health outcomes . DATA SOURCES The MEDLINE data base was search ed for articles published from 1983 to 1993 using " physician-patient relations " as the primary medical subject heading . Several bibliographies and conference proceedings were also review ed . STUDY SELECTION R and omized controlled trials ( RCTs ) and analytic studies of physician-patient communication in which patient health was an outcome variable . DATA EXTRACTION The following information was recorded about each study : sample size , patient characteristics , clinical setting , elements of communication assessed , patient outcomes measured , and direction and significance of any association found between aspects of communication and patient outcomes . DATA SYNTHESIS Of the 21 studies that met the final criteria for review , 16 reported positive results , 4 reported negative ( i.e. , nonsignificant ) results , and 1 was inconclusive . The quality of communication both in the history-taking segment of the visit and during discussion of the management plan was found to influence patient health outcomes . The outcomes affected were , in descending order of frequency , emotional health , symptom resolution , function , physiologic measures ( i.e. , blood pressure and blood sugar level ) and pain control . CONCLUSIONS Most of the studies review ed demonstrated a correlation between effective physician-patient communication and improved patient health outcomes . The components of effective communication identified by these studies can be used as the basis both for curriculum development in medical education and for patient education programs . Future research should focus on evaluating such educational programs OBJECTIVE The purpose of this study is to determine whether patient activation is a changing or changeable characteristic and to assess whether changes in activation also are accompanied by changes in health behavior . STUDY METHODS To obtain variability in activation and self-management behavior , a controlled trial with chronic disease patients r and omized into either intervention or control conditions was employed . In addition , changes in activation that occurred in the total sample were also examined for the study period . Using Mplus growth models , activation latent growth classes were identified and used in the analysis to predict changes in health behaviors and health outcomes . DATA SOURCES Survey data from the 479 participants were collected at baseline , 6 weeks , and 6 months . PRINCIPAL FINDINGS Positive change in activation is related to positive change in a variety of self-management behaviors . This is true even when the behavior in question is not being performed at baseline . When the behavior is already being performed at baseline , an increase in activation is related to maintaining a relatively high level of the behavior over time . The impact of the intervention , however , was less clear , as the increase in activation in the intervention group was matched by nearly equal increases in the control group . CONCLUSIONS Results suggest that if activation is increased , a variety of improved behaviors will follow . The question still remains , however , as to what interventions will improve activation OBJECTIVE A case study at the department for heart surgery of an Austrian University Hospital in 2001 , examined the outcome of improved communication aim ed at empowering patients to be more effective co-producers of recuperation after surgery . METHODS Evaluated were the effects of a training program for developing communication skills of health professionals ( physicians , physiotherapists , and nurses ) along with a reorganization of patient information schemes . The clinical outcomes after four types of surgery ( bypass , stent , artificial valve insertion and combination of these ) were observed in 100 patients without ( control group ) and 99 with the intervention administered ( intervention group ) . Two objective and two subjective health outcome parameters were selected for analysis : care level adjusted length of stay in hospital , frequency of post-surgery complications , subjective health , subjective satisfaction with care received . Self-administered breathing exercises were measured as an intermediary outcome parameter . RESULTS In the intervention group length of hospital stay was shorter ( by 1 day ) , incidence of post-surgery tachyarrhythmia was reduced ( by 15 % ) , transfer to less intensive care levels was faster and patient ratings for communicative quality of care by doctors and nurses were improved . CONCLUSION Professional communication aim ed at empowering patients to act as co producers can indeed have an effect on clinical outcome . PRACTICE IMPLICATION S Staff training and reorganization of communication schemes can be an effective intervention in hospital care Background : Preventive guidelines on cardiovascular risk management recommend lifestyle changes . Support for lifestyle changes may be a useful task for practice nurses , but the effect of such interventions in primary prevention is not clear . We examined the effect of involving patients in nurse-led cardiovascular risk management on lifestyle adherence and cardiovascular risk . Methods : We performed a cluster r and omized controlled trial in 25 practice s that included 615 patients . The intervention consisted of nurse-led cardiovascular risk management , including risk assessment , risk communication , a decision aid and adapted motivational interviewing . The control group received a minimal nurse-led intervention . The self-reported outcome measures at one year were smoking , alcohol use , diet and physical activity . Nurses assessed 10-year cardiovascular mortality risk after one year . Results : There were no significant differences between the intervention groups . The effect of the intervention on the consumption of vegetables and physical activity was small , and some differences were only significant for subgroups . The effects of the intervention on the intake of fat , fruit and alcohol and smoking were not significant . We found no effect between the groups for cardiovascular 10-year risk . Interpretation : Nurse-led risk communication , use of a decision aid and adapted motivational interviewing did not lead to relevant differences between the groups in terms of lifestyle changes or cardiovascular risk , despite significant within-group differences OBJECTIVE To assess the effect of additional training of practice nurses and general practitioners in patient centred care on the lifestyle and psychological and physiological status of patients with newly diagnosed type 2 diabetes . DESIGN Pragmatic parallel group design , with r and omisation between practice teams to routine care ( comparison group ) or routine care plus additional training ( intervention group ) ; analysis at one year , allowing for practice effects and stratifiers ; self reporting by patients on communication with practitioners , satisfaction with treatment , style of care , and lifestyle . SETTING 41 practice s ( 21 in intervention group , 20 in comparison group ) in a health region in southern Engl and . SUBJECTS 250/360 patients ( aged 30 - 70 years ) diagnosed with type 2 diabetes and completing follow up at one year ( 142 in intervention group , 108 in comparison Output:	Few interventions targeting patient-practitioner communication have assessed the impact on cardiovascular-related clinical outcomes , limiting the ability to determine effectiveness .
MS212029	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Publication bias , sometimes known as the " file-drawer problem " or " funnel-plot asymmetry , " is common in empirical research . The authors review the implication s of publication bias for quantitative research synthesis ( meta- analysis ) and describe existing techniques for detecting and correcting it . A new approach is proposed that is suitable for application to meta-analytic data sets that are too small for the application of existing methods . The model estimates parameters relevant to fixed-effects , mixed-effects or r and om-effects meta- analysis contingent on a hypothetical pattern of bias that is fixed independently of the data . The authors illustrate this approach for sensitivity analysis using 3 data sets adapted from a commonly cited reference work on research synthesis ( H. M. Cooper & L. V. Hedges , 1994 ) The effectiveness of a therapist-supported Internet intervention program for tinnitus distress in an industrial setting was evaluated using a cluster r and omised design . Fifty-six Australian employees of two industrial organisations were r and omly assigned , based on their work site ( 18 work sites from BP Australia and five from BHP Billiton ) , to either a cognitive behavioural therapy ( CBT ) program or an information-only control program . Participants were assessed at pre- and postprogram , measuring tinnitus distress , depression , anxiety , stress , quality of life , and occupational health . The CBT program was not found to be superior to the information program for treating tinnitus distress . A high attrition rate and small sample size limit the generalisability of the findings , and further developments of the program and assessment process are needed to enhance engagement and compliance BACKGROUND Although effective therapies for social phobia exist , many individuals refrain from seeking treatment owing to the embarrassment associated with help-seeking . Internet-based cognitive-behavioural self-help can be an alternative , but adherence is a problem . AIMS To evaluate a 9-week programme of internet-based therapy design ed to increase treatment adherence by the addition of short weekly telephone calls , nine in all , with a total duration of 95 min . METHOD In a r and omised controlled trial the effects of internet-based cognitive-behavioural therapy in the treatment group ( n=29 ) were compared with a waiting-list control group ( n=28 ) . RESULTS Compared with the control group the treated participants experienced greater reductions on measures of general and social anxiety , avoidance and depression . Adherence to treatment was high , with 93 % finishing the complete treatment package . One year later all improvements were maintained . CONCLUSIONS This study provides evidence to support the use of internet-based treatment supplemented by short , weekly telephone calls OBJECTIVE Using a r and omized group design , the efficacy of an outpatient cognitive-behavioral Tinnitus Coping Training ( TCT ) was compared to two minimal-contact ( MC ) interventions . METHODS TCT was conducted in a group format with 11 sessions ( total n=43 ) . One MC [ MC-E ( education ) , n=16 ] consisted of two group sessions in which education on tinnitus was presented and self-help strategies were introduced . The second MC [ MC-R ( relaxation ) , n=16 ] comprised four sessions . Besides education , music-supported relaxation was suggested as self-help strategy and audiotapes with relaxing music were provided . Furthermore , a waiting-list control group was installed ( WC , n=20 ) . Data were assessed at baseline ( pretherapy ) and at posttherapy period . Only TCT was additionally evaluated at a 6-month and a 12-month follow-up . Several outcome variables ( e.g. , awareness of tinnitus ) were recorded in a tinnitus diary . Tinnitus coping and disability due to tinnitus were assessed by question naires . Subjective ratings of improvement were also requested from the patients . Furthermore , inventories of psychopathology were given to the patients . RESULTS Findings reveal highly significant improvements in TCT in comparison to the control group ( WC ) . MC interventions do not differ significantly from each other , but are superior to WC in a few domains of outcome . Outcome in TCT is somewhat superior to combined MC interventions in two domains of data , but not regarding disability reduction . Effect sizes , nevertheless , indicate distinct differences in degree of improvement , with TCT achieving the best results . CONCLUSIONS A sequential scheme for the treatment of chronic tinnitus is discussed on the basis of cost-effectiveness considerations Tinnitus distress can be reduced by means of cognitive-behavior therapy ( CBT ) , and the treatment can be delivered in different ways . The most recent format is Internet-based self-help . The aim of this study was to compare this treatment ( n= 26 ) with st and ard group-based CBT ( n=25 ) in a r and omized controlled trial . Outcomes on self-report inventories measuring tinnitus distress were evaluated immediately after and 1 year after treatment . Results showed that both groups had improved , and there were few differences between them . The effect size for the Internet treatment was d=0.73 ( 95 % CI=0.16 - 1.30 ) and for the group treatment was d=0.64 ( 95 % CI=0.07 - 1.21 ) . The Internet treatment consumed less therapist time and was 1.7 times as cost-effective as the group treatment . At pretreatment patients rated the Internet treatment as less credible than the group treatment . In conclusion , Internet treatment for tinnitus distress merits further investigation , as the outcomes achieved are promising Objective The aim of this study was to investigate if cognitive behavior therapy ( CBT ) provided via the Internet results in significant decreases of distress in individuals with tinnitus . Methods Participants were recruited through Web pages and newspaper articles and thereafter r and omly allocated to a CBT self-help manual in six modules or to a waiting-list control group ( WLC ) . All treatment and contact with participants were conducted via the Internet with Web pages and E-mail correspondence . Participants were 117 individuals with tinnitus of duration of more than 6 months . In the first r and omized controlled phase of the study , 26 completed all stages of treatment ( 51 % dropout ) , and 64 of the WLC group completed measures . At 1-year follow-up , all participants had been offered the program and 96 provided outcome measures ( 18 % dropout rate from baseline ) . Tinnitus-related problems were assessed before and after treatment and at the 1-year follow-up . Daily diary ratings were included for 1 week before and 1 week following the treatment period . Results Tinnitus-related distress , depression , and diary ratings of annoyance decreased significantly . Immediately following the r and omized controlled phase ( with a WLC ) , significantly more participants in the treatment group showed an improvement of at least 50 % on the Tinnitus Reaction Question naire . At the uncontrolled follow-up , 27 ( 31 % ) of all participants had achieved a clinical ly significant improvement . Conclusions CBT via the Internet can help individuals decrease annoyance associated with tinnitus . High dropout rates or delay in completing treatment can be a characteristic of treatment studies using the Internet but should be contrasted with the cost effectiveness and accessibility of the Internet UNLABELLED We conducted a r and omized clinical trial to examine the relative effectiveness of two psychological interventions for treating tinnitus . People with tinnitus were initially offered a single session of psychoeducation about tinnitus , followed 2 months later by six weekly sessions of either mindfulness or relaxation training . Results indicated benefits from psychoeducation in reducing negative emotions , rumination and psychological difficulties of living with tinnitus . These effects were maintained or enhanced by mindfulness training that also emphasized acceptance , although they were eroded in the relaxation condition over the follow-up . Mediating processes are discussed , and suggestions for refining clinical interventions for this population are offered . KEY PRACTITIONER MESSAGE The present results suggest that mindfulness training might constitute a useful addition to psychoeducation for interventions targeting the psychological consequences of tinnitus The study compared the effects of Acceptance and Commitment Therapy ( ACT ) with Tinnitus Retraining Therapy ( TRT ) on tinnitus impact in a r and omised controlled trial . Sixty-four normal hearing subjects with tinnitus were r and omised to one of the active treatments or a wait-list control ( WLC ) . The ACT treatment consisted of 10 weekly 60 min sessions . The TRT treatment consisted of one 150 min session , one 30 min follow-up and continued daily use of wearable sound generators for a recommended period of at least 8h/day for 18 months . Assessment s were made at baseline , 10 weeks , 6 months and 18 months . At 10 weeks , results showed a superior effect of ACT in comparison with the WLC regarding tinnitus impact ( Cohen 's d=1.04 ) , problems with sleep and anxiety . The results were mediated by tinnitus acceptance . A comparison between the active treatments , including all assessment points , revealed significant differences in favour of ACT regarding tinnitus impact ( Cohen 's d=0.75 ) and problems with sleep . At 6 months , reliable improvement on the main outcome measure was found for 54.5 % in the ACT condition and 20 % in the TRT condition . The results suggest that ACT can reduce tinnitus distress and impact in a group of normal hearing tinnitus patients BACKGROUND Chronic tinnitus is a frequent symptom presentation in clinical practice . No drug treatment to date has shown itself to be effective . The aim of the present study was to investigate the effects of cognitive behavioural therapy and meditation in tinnitus sufferers . METHODOLOGY Patients were selected from a dedicated tinnitus clinic in the Welsh Hearing Institute . A waiting list control design was used . Twenty-five chronic tinnitus sufferers were consecutively allocated to two groups , one receiving a cognitive behavioural therapy/meditation intervention of four one hour sessions with the other group waiting three months and subsequently treated in the same way , thereby acting as their own control . The main outcome was measured using the Hallam tinnitus question naire . A four to six month follow up was conducted . RESULTS These showed significant statistical reductions in tinnitus variables both in the active and also in the control group . Post-therapy , no significant change was found after the waiting list period . The improvement was maintained at the four to six month period . CONCLUSION The positive findings give support for the use of cognitive behavioural therapy/meditation for chronic tinnitus sufferers Acute tinnitus can lead to substantial distress and eventually result in long-lasting impairment . The aim of this study was to compare the efficacy of a cognitive-behavioural intervention ( delivered as Internet self-management , bibliotherapy or group training ) to the information-only control condition . Applicants suffered from subjective tinnitus for up to six months , were between 18 and 75 years old and received no other tinnitus-related psychological treatment . A total of 304 participants were r and omly assigned to one of the four study arms . Tinnitus distress , depressive symptoms , psychosomatic discomfort and treatment satisfaction were assessed . At the post- assessment tinnitus distress was significantly lower in the Internet and the group training conditions compared to the control condition . Inter-group effect sizes were moderate to large . At follow-up , all active training conditions showed significantly reduced tinnitus distress compared to the control condition ( intention-to-treat analysis ) . An additional completer analysis showed a significant reduction in tinnitus distress only for the group condition . All effect sizes were moderate . There were no differences regarding psychosomatic discomfort , but depressive symptoms were reduced in the group condition at the post- assessment ( intention-to-treat analysis ) . Treatment satisfaction was significantly higher in the training conditions . The dropout rate was 39 % . The present study shows that distress can be reduced as early as the acute stadium and that minimal-contact interventions are a promising way to do this . In particular , the Internet and group conditions led to a large , immediate decrease in distress , and the participants were highly satisfied with the training In this study conducted in the French-speaking part of Switzerl and , 52 individuals with social phobia were r and omly assigned either to an Internet-based cognitive-behavioral treatment with minimal contact with therapists via e-mail or to a waiting-list control group . Significant differences between the two groups were found at posttreatment on all primary outcome measures ( social anxiety measures ) and on two of the secondary outcome measures ( general symptomatology , therapy goal attainment ) . On average , within-groups effect sizes were large for the primary outcomes ( Cohen 's d=0.82 ) and for secondary outcomes ( Cohen 's d=1.04 ) . Moreover , subjects in the treatment group fulfilled the criteria of clinical ly significant improvement significantly more often than subjects in the control group on all measured dimensions ( 58 % vs. 20 % ) . Users ' acceptance of the program was high . The results from the present study lend further support to the hypothesis that Internet-delivered interventions with minimal therapist contact are a promising treatment approach to social phobia OBJECTIVE Tinnitus distress can be reduced by means of cognitive-behavior therapy ( CBT ) . To compensate for the shortage of CBT therapists , we aim ed , in this study , to investigate the effects of a CBT-based self-help book guided by brief telephone support . METHODS Seventy-two patients were r and omized either to a self-help book and seven weekly phone calls or to a wait-list control condition , later on receiving the self-help book with less therapist support . The dropout rate was 7 % . Follow-up data 1 year after completion of treatment were also collected ( 12 % dropout ) . The Tinnitus Reaction Question naire ( TRQ ) was the main outcome measure , complemented with daily ratings of tinnitus and measures of insomnia , anxiety , and depression . RESULTS On the TRQ , significant reductions were found in the treatment group both immediately following treatment and at 1-year follow-up . In the treatment group , 32 % reached the criteria for clinical significance ( Output:	There was no difference to the face-to-face controls ( group treatment ) . Sensitivity analysis revealed that there might be a publication bias regarding the comparison to the face-to-face control . However , the results suggest that CBT self-help interventions are an effective treatment for tinnitus distress .
MS212030	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVES To assess multiple psychometric characteristics of a new stroke outcome measure , the Stroke Impact Scale ( SIS ) , using Rasch analysis , and to identify and remove misfitting items from the 8 domains that comprise the SIS . DESIGN Secondary analysis of 3-month outcomes for the Glycine Antagonist in Neuroprotection ( GAIN ) Americas r and omized stroke trial . SETTING A multicenter r and omized trial performed in 132 centers in the United States and Canada . PARTICIPANTS A total of 696 individuals with stroke who were community-dwelling and independent prior to acute stroke . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Rasch analysis was performed using WINSTEPS , version 3.31 , to evaluate 4 psychometric characteristics of the SIS : ( 1 ) unidimensionality or fit ( the extent to which items measure a single construct ) , ( 2 ) targeting ( the extent to which the items are of appropriate difficulty for the sample ) , ( 3 ) item difficulty ( the ordering of items from least to most difficult to perform ) , and ( 4 ) separation ( the extent to which the items distinguish distinct levels of functioning within the sample ) . RESULTS ( 1 ) Within each domain , most of the items measured a single construct . Only 3 items misfit the constructs and were deleted ( " add and subtract numbers , " " get up from a chair , " " feel emotionally connected " ) and 2 items ( " h and le money , " " manage money " ) misfit the combined physical domain . These items were deleted to create SIS , version 3.0 . ( 2 ) Overall , the items are well targeted to the sample . The physical and participation domains have a wide range of items that capture difficulties that most individuals with stroke experience in physical and role functions , while the memory , emotion , and communication domains include items that capture limitations in the most impaired patients . ( 3 ) The order of items from less to more difficult was clinical ly meaningful . ( 4 ) The individual physical domains differentiated at least 3 ( high , average , low ) levels of functioning and the composite physical domain differentiated more than 4 levels of functioning . However , because difficulties with communication , memory , and emotion were not as frequently reported and difficulties with h and function were more frequently reported , these domains only differentiated 2 ( high , low ) to 3 ( high , average , low ) strata of patients . Time from stroke onset to administration of the SIS had little effect on item functioning . CONCLUSION Rasch analysis further established the validity of the SIS . The domains are unidimensional , the items have an excellent range of difficulty , and the domain scores differentiated patients into multiple strata . The activities of daily living/instrumental activities of daily living , mobility , strength , composite physical , and participation domains have the most robust psychometric characteristics . The composite physical domain is most able to discriminate difficulty in function in individuals after stroke , while the communication , memory , and emotion domain items only capture limitations in function in the more impaired groups of patients Background and Purpose — This study compared the psychometric properties of 3 clinical balance measures , the Berg Balance Scale ( BBS ) , the Balance subscale of the Fugl-Meyer test ( FM-B ) , and the Postural Assessment Scale for Stroke Patients ( PASS ) , in stroke patients with a broad range of neurological and functional impairment from the acute stage up to 180 days after onset . Methods — One hundred twenty-three stroke patients were followed up prospect ively with the 3 balance measures 14 , 30 , 90 , and 180 days after stroke onset ( DAS ) . Reliability ( interrater reliability and internal consistency ) and validity ( concurrent validity , convergent validity , and predictive validity ) of each measure were examined . A comparison of the responsiveness of each of the 3 measures was made on the basis of the entire group of patients and 3 separate groups classified by degree of neurological severity . Results — The FM-B and BBS showed a significant floor or ceiling effect at some DAS points , whereas the PASS did not show these effects . The BBS , FM-B , and PASS all had good reliability and validity for patients at different recovery stages after stroke . The results of effect size demonstrated fair to good responsiveness of all 3 measures within the first 90 DAS but , as expected , only a low level of responsiveness at 90 to 180 DAS . The PASS was more responsive to changes in severe stroke patients at the earliest period after stroke onset , 14 to 30 DAS . Conclusions — All 3 measures tested showed very acceptable levels of reliability , validity , and responsiveness for both clinicians and research ers . The PASS showed slightly better psychometric characteristics than the other 2 measures OBJECTIVE The objective of this study was to evaluate the strengths and weaknesses of a group support program and a home visiting program for family caregivers of stroke patients . It also examined the best fit between intervention variant and family caregiver and patient characteristics . van den Heuvel 's previous effect study showed positive effects of the same intervention program , but unlike our present study differences between the two support variants could not be measured . METHODS Of 257 family caregivers who were included and r and omly assigned to an intervention variant or a control group , 127 family caregivers completed the intervention in either the group program or the home visiting program . RESULTS Evaluation data showed that both intervention variants had been helpful and feasible , but home visit participants missed peer contact and follow-up contacts were missed in both intervention programs . In comparison to the home visiting program , the group program participants showed more benefit especially with respect to informational and emotional components . Caregivers ' preference for type of intervention revealed that both types of intervention had its supporters . Those that preferred the group program could be clearly characterised : they were burdened , lived with a more psychologically h and icapped relative , were using active coping strategies more frequently or lived in a region which is considered to be more sociable . CONCLUSION The present study adds extensively to van den Heuvel 's effect study with respect to discriminative aspects of group and home intervention programs and their respective benefits for specific family caregiver groups . PRACTICE IMPLICATION S In order to suitably match an intervention type with specific caregiver characteristics the intervention provider should utilize caregiver self- selection or undertake professional screening of caregiver burden . Telephone contacts should be offered in addition to the interventions UNLABELLED Several studies showed that Constraint-Induced Movement Therapy ( CIMT ) leads to a lasting improvement of upper extremity function in chronic stroke patients . The original technique includes an intensive 2-week program with 6 hours of daily physiotherapy . Due to high expenses it is difficult to implement this concept in outpatient care . PURPOSE The objective of this study was to evaluate the effects of a 4-week homebased CIMT program among chronic stroke patients and to compare them with a 2-week CIMT program , based on the original technique . METHODS Seven adults with chronic stroke completed a newly developed variant of CIMT , performed at patients ' homes ( group1 , CIMThome ) , supervised by an instructed family member , constraint of unaffected h and for a target of 60 % of waking hours . The intervention was analysed with pre- , post-treatment and 6-month follow-up measurements . Effects on improvement in upper extremity function were compared with patients treated according to the original protocol ( group2 , CIMTclassic ) , supervised by a physiotherapist , constraint of unaffected h and for a target of 90 % of waking hours . RESULTS Patients from both groups showed almost identical improvement of their motor function according to scores on the Wolf Motor Function Test ( WMFT ) and the Motor Activity Log ( MAL ) immediately after the treatment period as well as at follow-up after 6 months . CONCLUSIONS Our study suggests that CIMThome is not only feasible but also as effective as CIMTclassic . This finding should be replicated in a larger prospect i ve r and omized trial to perform a non-inferiority analysis Background and Purpose — This proof-of-concept trial investigated the effects of an 8-week program of caregiver-mediated exercises commenced in hospital combined with tele-rehabilitation services on patient self-reported mobility and caregiver burden . Methods — Sixty-three hospitalized stroke patients ( mean age 68.7 , 64 % female ) were r and omly allocated to an 8-week caregiver-mediated exercises program with e-health support or usual care . Primary outcome was the Stroke Impact Scale mobility domain . Secondary outcomes included length of stay , other Stroke Impact Scale domains , readmissions , motor impairment , strength , walking ability , balance , mobility , ( extended ) activities of daily living , psychosocial functioning , self-efficacy , quality of life , and fatigue . Additionally , caregiver ’s self-reported fatigue , symptoms of anxiety , self-efficacy , and strain were assessed . Assessment s were completed at baseline and at 8 and 12 weeks . Results — Intention-to-treat analysis showed no between-group difference in Stroke Impact Scale mobility ( P=0.6 ) ; however , carers reported less fatigue ( 4.6 , confidence interval [ CI ] 95 % 0.3–8.8 ; P=0.04 ) and higher self-efficacy ( −3.3 , CI 95 % −5.7 to −0.9 ; P=0.01 ) at week 12 . Per- protocol analysis , examining those who were discharged home with tele-rehabilitation demonstrated a trend toward improved mobility ( −9.8 , CI 95 % −20.1 to 0.4 ; P=0.06 ) , significantly improved extended activities of daily living scores at week 8 ( −3.6 , CI 95 % −6.3 to −0.8 ; P=0.01 ) and week 12 ( 3.0 , CI 95 % −5.8 to −0.3 ; P=0.03 ) , a 9-day shorter length of stay ( P=0.046 ) , and fewer readmissions over 12 months ( P<0.05 ) . Conclusions — Caregiver-mediated exercises supported by tele-rehabilitation show promise to augment intensity of practice , result ing in improved patient-extended activities of daily living , reduced length of stay with fewer readmissions post stroke , and reduced levels of caregiver fatigue with increased feelings of self-efficacy . The current findings justify a larger definite phase III r and omized controlled trial . Clinical Trial Registration — URL : http://www.anzctr.org.au . Unique identifier : ACTRN12613000779774 Background Most acute stroke patients with disabilities do not receive recommended rehabilitation following discharge to the community . Functional and social barriers are common reasons for non-adherence to post-discharge rehabilitation . Home rehabilitation is an alternative to centre-based rehabilitation but is costlier . Tele-rehabilitation is a possible solution , allowing for remote supervision of rehabilitation and eliminating access barriers . The objective of the Singapore Tele-technology Aided Rehabilitation in Stroke ( STARS ) trial is to determine if a novel tele-rehabilitation intervention for the first three months after stroke admission improves functional recovery compared to usual care . Methods / design This is a single blind ( evaluator blinded ) , parallel , two-arm r and omised controlled trial study design involving 100 recent stroke patients . The inclusion criteria are age ≥40 years , having caregiver support and recent stroke defined as stroke diagnosis within 4 weeks . Consenting participants will be r and omized with varying block size of 4 or 6 assuming a 1:1 treatment allocation with the participating centre as the stratification factor . The baseline assessment will be done within 4 weeks of stroke onset , followed by follow-up assessment s at 3 and 6 months . The tele-rehabilitation intervention lasts for 3 months and includes exercise 5-days-a-week using an iPad-based system that allows recording of daily exercise with video and sensor data and weekly video-conferencing with tele-therapists after data review . Those allocated to the control group will receive usual care . The primary outcome measure is improvement in life task ’s social activity participation at three months as measured by the disability component of the Jette Late Life Functional and Disability Instrument ( LLFDI ) . Secondary outcome variables consist of gait speed ( Timed 5-Meter Walk Test ) and endurance ( Two-Minute Walk test ) , performance of basic activities of daily living ( Shah-modified Barthel Index ) , balance confidence ( Activities-Specific Balance Confidence Scale ) , patient self-reported health-related quality -of-life [ Euro-QOL ( EQ-5D ) ] , health service utilization ( Singapore Stroke Study Health Service Utilization Form ) and caregiver reported stress ( Zarit Caregiver Burden Inventory ) . Discussion The goal of this trial is to provide evidence on the potential benefit and cost-effectiveness of this novel tele-rehabilitation programme which will guide health care decision-making and potentially improve performance of post-stroke community-based rehabilitation . Trial Registration This trial protocol was registered under Clinical Trials.gov on 18 July 2013 as study title “ The Singapore Tele-technology Aided Rehabilitation in Stroke ( STARS ) Study ” ( ID : The STARS Study , Clinical Trials.gov Identifier : NCT01905917 ) Background and Purpose — One way that stroke units may improve outcome is by reducing complications of immobility through early mobilization ; however , this intervention needs testing . The purpose of this study was to determine the physical activity patterns of stroke patients managed within acute stroke units as a first step in developing an early mobilization protocol . Methods — We recruited 64 patients within 14 days after stroke from 5 metropolitan stroke units and observed them for 2 consecutive days at 10-minute intervals between the hours of 8 am and 5 pm . At each observation , we ascertained physical activity , location , and other person(s ) present . Therapists recorded therapy details . Results — The 58 patients who completed the study had a mean age of 71.3 years . Stroke severity ranged from mild ( National Institutes of Health Stroke Scale score , 1 ) to severe ( score , 27 ) , and mean time after stroke at observation was 5.6 days ( range , 0 to 1 Output:	There is very low- to moderate- quality evidence that CME may be a valuable intervention to augment the pallet of therapeutic options for stroke rehabilitation . Future high- quality research should determine whether CME interventions are (cost-)effective
MS212031	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To assess the ability of mifepristone to prime the cervix adequately and induce labor in pregnant women at term ; and when mifepristone alone proves insufficient , to determine whether oral misoprostol taken 48 h following mifepristone administration is effective in inducing labor . METHODS In this prospect i ve study 50 pregnant women at term with an unfavorable cervix were given 400 mg of mifepristone orally and allowed to return home . If labor did not start within 48 h , the women were admitted and induction was continued with 50 mug of misoprostol , a prostagl and in ( PG ) E1 analogue , taken orally every 4 h. The 50 controls , who were matched prospect ively for parity and pregnancy duration , underwent labor induction according to the routine administration of 3-mg tablets of PGE2 vaginally . RESULTS In the study group , 66 % of the women entered labor spontaneously or had a sufficiently ripened cervix within 48 h of taking mifepristone . However , there was no difference in time between prostagl and in administration and delivery between the control group and the 34 % of women who required misoprostol in the study group . In the study group , the cesarean section rate was significantly lower among the women whose labor was induced with mifepristone alone than among those who required misoprostol . There were no differences overall in obstetric or neonatal outcomes between the study and control groups . CONCLUSIONS In this pilot sample , 400 mg of mifepristone was effective in inducing cervical changes and labor . Although there were no adverse effects using oral misoprostol in combination with mifepristone , labor was more difficult to induce in the women who did not respond to mifepristone alone , and these women had a higher operative delivery rate The value of gentle , unilateral breast stimulation in the ripening of cervix and induction of labour was studied . Three hundred patients with uncomplicated term pregnancies , ( 38 - 42 weeks ) were recruited into the study , consisting of three separate r and omised double blind prospect i ve trials . The first trial was to evaluate the effectiveness of breast stimulation in ripening the cervices of 200 term primigravid patients . There was a mean change of 3.90 + /- 2.39 points in cervical score among the study group compared to 0.50 + /- 0.67 among the control group . Thirty-three per cent of the study group went into labour when compared with 4 % among the control group . In a second study of cross-over trial involving 78 of the original 200 patients , the study ( ex-control ) group had a mean change in cervical score of 3.84 + /- 2.24 when compared with the control ( ex- study ) group , ( 1.43 + /- 1.08 ) . In a third study involving 100 multiparous patients , a mean change in cervical score of 2.74 + /- 1.16 was observed in the study group when compared with the control group , 0.92 + /- 1.07 . Forty-six per cent of the patients went into labour compared with 12 % in the control group . All findings were highly significant and there were no maternal or fetal side-effects . The study confirmed the efficacy of breast stimulation in cervical ripening and induction of labour Two hundred consecutive women with uncomplicated pregnancies , at or within 4 days of their expected date of confinement , were prospect ively r and omized into 2 groups . One group had expectant management , with twice weekly surveillance tests , while the other group had 3 mg of vaginal prostagl and in E2 as outpatient treatment . There were 104 women in the expectant group and 70 in the induction group ( 26 women allocated to induction preferred no treatment ) . The average number of days to delivery was 1.6 in the induction group and 5.2 in the expectant group ( p < 0.001 ) . While meconium was much less frequent in the induction group ( p < 0.002 ) , all other outcome measures , including cesarean section rates , incidence of macrosomia , and Apgar scores , were similar in the two groups In a prospect i ve r and omized study , pregnancies with unfavorable cervix and well established gestational age of at least 42 weeks were selected for management by either antepartum fetal testing or prostagl and in gel induction of labor . Of the 108 pregnancies studied , 57 ( 53 % ) had labor induced and 51 ( 47 % ) continued without intervention . Comparison of the two groups showed no difference in meconium staining , fetal distress , length of first stage of labor , the need for intervention , or the mode of delivery . In terms of Apgar score the neonatal outcome was not significantly different but a greater proportion of the babies ( 7.8 % versus 1.8 % ) in the noninduced group required intubation . Our data show that there is no particular advantage in letting the pregnancy go beyond 42 completed weeks of gestation especially if prostagl and in is available for induction of labor OBJECTIVE To determine whether outpatient administration of intracervical prostagl and in ( PG ) E2 gel decreases the interval to delivery and duration of labor . METHODS A r and omized , double-blind , placebo-controlled trial compared the intracervical placement of 0.5 mg PGE2 gel with placebo in 61 pregnant women at 38 weeks ' or greater gestation with Bishop scores less than 9 . Transvaginal cervical length , fetal fibronectin , and Bishop score were assessed before gel placement . Subjects were then allowed to go into spontaneous labor unless an indication for induction developed . RESULTS Thirty women were assigned to PGE2 and 31 to placebo . There were no significant demographic differences between the groups and there were no differences in cervical length , fetal fibronectin status , or Bishop scores . Fifteen women in the PGE2 group and five in the placebo group went into labor and delivered within the first 2 days after gel placement ( P = .007 ) . The median interval to delivery was significantly shorter in the PGE2 group , at 2.5 days , compared with placebo , at 7 days ( P = .02 ) . Nulliparas in the PGE2 group had a median interval to delivery of 2 days , compared with 7 days for nulliparas receiving placebo ( P = .03 ) . Active phases of labor were significantly shorter in the PGE2 group and for women with a negative fetal fibronectin test who received PGE2 . CONCLUSION Outpatient administration of intracervical PGE2 gel shortened intervals to delivery and shortened labor Objective To compare the effects of 50 mg or 200 mg of oral mifepristone with placebo on cervical ripening and induction of labor in primigravid women at term with unfavorable cervices . Methods This was a double-blind study in which 80 primigravidae at term with a modified Bishop score of 4 or less were r and omly assigned to one of three treatment groups . They were assessed at 24-hour intervals for 72 hours , after which labor was induced if it had not occurred spon-taneously . Results Two hundred milligrams of mifepristone result ed in a favorable cervix ( with a Bishop score greater than 6 or in spontaneous labor ) in significantly more women than placebo ( P = .01 ) . An improvement in cervical ripening was seen in the group given 50 mg of mifepristone , but this was not statistically significant . There were more cesarean deliveries performed for fetal distress in the group treated with 200 mg of mifepristone than placebo , but this was not statistically significant and was not associated with any differences between groups in terms of neonatal outcome . Conclusion Mifepristone , a progesterone antagonist , is known to cause softening and dilation of the human early pregnant cervix and an increase in uterine activity . It is theoretically attractive for use as an adjunct in cervical priming and labor induction . In this study , 200 mg of mifepristone was significantly more likely to result in a favorable cervix than placebo Background There is increasing interest in carrying out pre-induction cervical ripening on an outpatient basis . However , there are concerns about the use of prostagl and ins , the agents commonly used in hospital setting s for this indication , because prostagl and ins induce uterine contractions that may lead to fetal hypoxia . Indeed , in a recent study we demonstrated abnormalities in 9 % of fetal heart rate tracings performed following prostagl and in induced cervical ripening at term . In contrast , we confirmed in the same study that isosorbide mononitrate ( IMN ) ( administered on an inpatient basis ) was both effective in inducing cervical ripening at term , and was associated with no associated fetal heart rate abnormalities . Methods / design The aim of this study is to determine whether IMN self administered by women on an outpatient basis improves the process of induction of labour . Specifically , we hypothesise that the use of outpatient IMN will result in a shorter inpatient stay before delivery , decreased costs to the health service and greater maternal satisfaction with ripening and induction of labour , compared with placebo treatment . In the study described here ( the " IMOP " study ) , women scheduled for induction of labour at term , and who require pre-induction cervical ripening will be r and omised to self-administer at home either IMN 40 mg , or a placebo , each vaginally , at 48 hours , 32 hours and 16 hours before scheduled hospital admission . After admission to hospital , treatment will revert to the usual induction of labour protocol . We will compare the primary outcomes of the elapsed time interval from hospital admission to vaginal delivery , the costs to the health service of induction of labour , and women 's experience of induction of labour in the two groups . Discussion This trial will provide evidence on the efficacy of outpatient IMN for pre-induction cervical ripening at term . We will study a formulation of IMN which is cheap and widely available . If the treatment is effective , acceptable to women , and cost effective , it could be implemented into obstetric practice worldwide . Trial registration The trial has been registered on the International St and ard R and omised Controlled Trial Number Register ( IS RCT N ) and given the registration number ISRTN39772441 OBJECTIVE Our purpose was to determine whether a protocol for outpatient induction is safe and effective for initiating labor . STUDY DESIGN A r and omized , double-blind , placebo-controlled trial was performed with 100 low-risk patients having well- date d pregnancies . Women with a Bishop score < or = 6 at 38 to 40 weeks ' gestation were administered either 2 mg of intravaginal prostagl and in E2 gel or placebo for 5 consecutive days as out patients while undergoing fetal monitoring . RESULTS The median interval from r and omization to delivery was 4 days in the prostagl and in E2 group ( range 0 to 28 days ) versus 10 days in the placebo group ( range 0 to 26 days , p = 0.002 ) . Twenty-seven of 50 patients ( 54 % ) in the prostagl and in E2 group were admitted for labor during the dosing interval compared with 10 placebo-treated patients ( 20 % , p = 0.001 ) . The mean gestational age at delivery was significantly reduced in the treatment group ( 39.9 + /- 1.0 weeks vs 40.5 + /- 0.99 weeks , p = 0.003 ) as was the incidence of post date s pregnancy ( 40 % vs 66 % , p = 0.016 ) . Hyperstimulation was observed in one prostagl and in E2-treated patient , but no intervention was required . CONCLUSIONS Outpatient low-dose prostagl and in E2 gel administration is effective for initiating labor in patients with an unfavorable cervix and appears safe if performed with adequate monitoring OBJECTIVE Within the obstetric community , several studies suggest that cervical ripening and labor induction after 40 weeks ' gestation leads to improved maternal and neonatal outcomes . The most effective drug regimen to safely promote labor has not been determined . METHOD Forty-nine subjects followed in an outpatient obstetrical clinic with pregnancies of at least 40 weeks ' gestation , and an unfavorable Bishop score were assigned r and omly to receive oral misoprostol 50 or 25 microg every 3 days for a maximum of three doses . RESULTS Twenty-three subjects received misoprostol 25 microg and 26 received 50 microg . The mean interval ( + /-st and ard deviation ) from start of cervical ripening to delivery was 2.4 days + /-0.3 vs. 3.9 days + /-0.7 for the 50 and 25 microg groups ( P<0.05 ) . No adverse events were noted . However , due to small sample size , less frequent adverse events may be missed . Type II errors can not be excluded . CONCLUSION In the prevention of post date pregnancy , out patients use of oral misoprostol 50 microg appears to result in earlier delivery , as compared to 25 microg Abstract Our purpose was to examine the hypothesis that corticosteroids , when administered intramuscularly , can enhance the labor process and reduce the time interval between the induction and the active phase . A r and omized , controlled study was conducted on 66 women with gestational age of 41 weeks and over and favorable cervix ( bishop score ≥ 7 ) . The study group ( n = 32 ) received 10 mg of dexamethasone phosphate intramuscularly in two doses at an interval of 12 hours , and the day after the enrolling administration intravenous oxytocin was given . The control group ( n = 33 ) received only intravenous oxytocin 24 hours after enrolling . The number Output:	Overall , the results demonstrate that outpatient induction of labour is feasible and that important adverse events are rare . There was no strong evidence that agents used to induce labour in outpatient setting s had an impact ( positive or negative ) on maternal or neonatal health . There was some evidence that , compared to placebo or no treatment , induction agents reduced the need for further interventions to induce labour , and shortened the interval from intervention to birth . We were unable to pool results on outcomes relating to progress in labour as studies tended to measure a very broad range of outcomes .There was no evidence that induction agents increased interventions in labour such as operative deliveries . Only two studies provided information on women 's views about the induction process , and overall there was very little information on the costs to health service providers of different methods of labour induction in outpatient setting s. AUTHORS ' CONCLUSIONS Induction of labour in outpatient setting s appears feasible . We do not have sufficient evidence to know which induction methods are preferred by women , or the interventions that are most effective and safe to use in outpatient setting
MS212032	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: INTRODUCTION The EuroTransplant " old to old " program establishes that patients older than 60 years can receive offers of organs from donors older than 60 years . The compromised function of these organs makes it a priority to preserve their initial kidney function . HYPOTHESIS Calcineurin-sparing protocol s using anti-IL-2 receptor ( IL-2R ) antibody induction ( Simulect ) may benefit initial kidney function in these patients , as assessed by the rates of delayed graft function and of rejection during the first month after transplant . PATIENTS AND METHODS A cohort of 15 consecutive elderly patients were prospect ively compared with 30 cadaveric kidney transplants in younger recipients . Study patients were induced with Simulect ( 20 mg , 30 minutes before reperfusion and 4 days after transplantation ) and steroids , delaying the introduction of CsA until the serum creatinine was below 3 mg/dL. The other cohort of patients were immunosuppressed with tacrolimus ( trough 8 to 12 ) , mycophenolats mofetil ( MMF , 1 g/d ) , and an identical taper of steroids . The analysis compared donor and recipient ages , mean cold ischemic time , incidence of initial kidney function ( diuresis in the first 24 h ) serum creatinine levels , glomerular filtration rate ( GFR ) , number of dialysis sessions , and rejection rate in the two groups . RESULTS Except for the donor and recipient ages ( 72 vs 54 in donors , and 67 versus 52 years in recipients ) , no significant differences were observed between the groups among the rates of acute rejection ( 6.6 % vs 13.2 % ) , delayed graft function ( 13.2 % required dialysis ) , or infection ( 6.6 % ) . Within 1 month all 45 grafts showed primary function with equal creatinine levels ( mean 1.65 ) . CONCLUSIONS Calcineurin-free protocol s using IL-2 therapy as the initial suppression allow patients in the " old to old " ET program to display equal results to cadaveric kidney transplants with initial treatment with calcineurin antagonists Background . Two open-label studies demonstrated that conversion from mycophenolate mofetil ( MMF ) to enteric-coated mycophenolate sodium ( EC-MPS ) significantly reduces gastrointestinal ( GI ) symptom burden and improves GI-specific health-related quality of life . Using a r and omized design , this study evaluated changes in GI symptoms and health-related quality of life in patients converted from MMF to EC-MPS versus patients who continued with MMF-based treatment . Methods . In this 4-week , multicenter , r and omized , prospect i ve , double-blind , parallel-group trial , renal transplant recipients with GI symptoms receiving MMF plus a calcineurin inhibitor±corticosteroids were r and omized to an equimolar dose of EC-MPS+MMF placebo or continue on their MMF-based regimen+EC-MPS placebo . The primary efficacy outcome was a change from baseline in total Gastrointestinal Symptom Rating Scale score of a minimally important difference of more than or equal to 0.3 . Results . Three hundred ninety-six patients ( EC-MPS group : n=199 ; MMF group : n=197 ) were included . A greater proportion of EC-MPS patients ( 62 % ) reached the primary efficacy outcome compared with MMF patients ( 55 % ) ; however , the difference was not statistically significant ( P=0.15 ) . EC-MPS patients had a significantly greater decrease in the Gastrointestinal Symptom Rating Scale indigestion syndrome dimension versus MMF patients . Within the subgroups of patients with diabetes , patients transplanted 6 to 12 months of study enrollment , and patients on steroids , a statistically significant greater proportion of EC-MPS versus MMF patients reached the primary efficacy outcome . Conclusions . Conversion from MMF to EC-MPS may be associated with improvements in presence and severity of GI symptoms , particularly in patients with indigestion , diabetes , on steroids , and in patients converted between 6 and 12 months posttransplantation This study was design ed to investigate the effect of tacrolimus ( FK506 ) and of cyclosporine ( CsA ) on tubular function in renal graft recipients . Patients were r and omised after renal transplantation to immunosuppressive treatment with FK506 ( n = 8) or CsA ( n = 8) . Patients had a mean age of 45.7 + /- 3.4 yr ; there was no difference in age , sex , HLA status or CMV mismatches . Neither was there any difference in the frequency of episodes of acute kidney failure between the groups , nor was there a significant difference in the frequency of episodes of kidney rejection within the first year . The mean FK506 level at the time lay at 14.7 + /- 14.4 ng/mL whole blood , and the mean CsA level at the time of study was 162 + /- 25 ng/mL whole blood . We performed renal function studies 6 months after transplantation : CIn , CPAH , NaHCO3 loading , and Na2SO4 loading . There was no significant impairment of GFR in patients treated with FK506 with 53.6 + /- 2.5 mL/min as compared to 58 + /- 6 mL in group 2 . Plasma renin activity ( 0.6 + /- 0.4 ng/mL vs 2.3 + /- 3 ; p < 0.01 ) and aldosterone ( 69 + /- 17 vs 157 + /- 28.2 pg/mL ; p < 0.05 ) were significantly decreased during treatment with FK506 . Fractional HCO3 excretion was low in both groups , indicating that bicarbonate reabsorption in the proximal nephron was unimpaired . Distal renal tubular acidosis was demonstrated in 4 patients of group 1 but in only 1 of group 2 . Potassium levels were slightly increased in patients treated with FK506 ( 5.4 + /- 0.2 mmoL/L ) as compared to cyclosporine ( 4.9 + /- 0.3 mmoL/L ; p < 0.05 ) . Distal hydrogen ion secretion , evaluated by the ability to increase urinary pCO2 in a highly alkaline urine , was impaired in patients treated with FK506 ( U-B pCO2 : 16.1 + /- 4 vs 36 + /- 5.8 ; p < 0.05 ) as compared to patients treated with CsA. The maximum acidification capability ( NAE ) was slightly lowered during therapy with FK506 ( 67.5 + /- 11.8 versus 86.6 + /- 16.5 mumoL/min , ns ) . We conclude that FK506 administration results in a decrease in the rate of hydrogen ion secretion by the collecting tubules . This defect was disclosed by the finding of a subnormal pCO2 in a highly alkaline urine . These results show that FK506 is able to induce distal tubular acidosis . Distal tubular acidosis is part of FK506 induced nephrotoxicity , the pathogenesis of this type of hyperkalemic metabolic acidosis found in patients treated with FK506 after renal transplantation has to be further eluci date Acute and chronic lesion scores on renal allograft protocol biopsies may predict long-term graft function . The aim of this study was to compare the effects of tacrolimus ( Tac ) and cyclosporine microemulsion ( CsA ) based immunosuppressive protocol s using protocol biopsies from well-functioning renal allografts . 35 consecutive renal transplant patients were r and omized to Tac ( n : 17 ) versus CsA ( n : 18 ) treatment arms . Patient age and sex , donor type and age , histocompatibility , cold ischemia time and prior delayed graft function were similar between the two groups . Treatment protocol consisted of prednisolone , azathioprine and Tac or CsA. Biopsies performed on the third , sixth and twelfth months were blindly evaluated by the same pathologist . The incidences of acute rejection ( AR ) episodes among CsA vs Tac groups were 33 % vs 29 % , respectively ( NS ) . The Creatinine level was lower in Tac than CsA , although it was not significant ( Table ) . Sub clinical AR and sub clinical chronic allograft nephropathy were detected on protocol biopsies in 3 ( 2 CsA , 1 Tac ) and 12 ( 7 CsA , 5 Tac ) patients , respectively . Acute lesion score at the third month PBx was significantly lower in the Tac group ( p < 0.05 ) . Chronic lesion scores in all biopsies were lower in the Tac group , although not significantly . The protocol biopsy findings suggest that graft injury may be less pronounced among the Tac group Background No study to date has evaluated the efficacy and safety of everolimus with reduced-exposure cyclosporine in Japanese de-novo renal transplant ( RTx ) patients . Methods This 12-month , multicenter , open-label study r and omized ( 1:1 ) 122 Japanese de-novo RTx patients to either an everolimus regimen ( 1.5 mg/day starting dose ( target trough : 3 to 8 ng/ml ) + reduced-dose cyclosporine ) or a mycophenolate mofetil ( MMF ) regimen ( 2 g/day + st and ard dose cyclosporine ) . All patients received basiliximab and corticosteroids . Key endpoints at month 12 were composite efficacy failure ( treated biopsy-proven acute rejection , graft loss , death , or loss to follow-up ) and renal function ( estimated glomerular filtration rate ; Modification of Diet in Renal Disease-4 ) . Results Clear cyclosporine exposure reduction was achieved in the everolimus group throughout the study ( 52 % reduction at month 12 ) . Month 12 efficacy failure rates showed everolimus 1.5 mg to be non-inferior to MMF ( 11.5 % vs. 11.5 % ) . The median estimated glomerular filtration rate at month 12 was 58.00 ml/minute/1.73 m2 in the everolimus group versus 55.25 ml/minute/1.73 m2 in the MMF group ( P = 0.063 ) . Overall , the incidence of adverse events was comparable between the groups with some differences in line with the known safety profile of the treatments . The everolimus group had a higher incidence of wound healing events and edema , whereas a higher rate of cytomegalovirus infections was reported in the MMF group . Conclusions This study confirmed the efficacy of everolimus 1.5 mg/day ( target trough : 3 to 8 ng/ml ) in Japanese RTx patients for preventing acute rejection , while allowing for substantial cyclosporine sparing . Renal function and safety findings were comparable with previous reports from other RTx population s . Trial registration Clinical Trials.gov number : Background The once-daily ( QD ) , prolonged-release formulation of tacrolimus has been shown to improve adherence versus twice-daily ( BD ) tacrolimus . Treatment nonadherence in transplant recipients has been associated with poor graft outcomes . Methods This open-label , parallel-group study r and omized adults with end-stage renal disease undergoing primary kidney transplantation or retransplantation to an initial dose of tacrolimus BD 0.2 mg/kg per day ( Arm 1 ; n=309 ) , QD 0.2 mg/kg per day ( Arm 2 ; n=302 ) , QD 0.3 mg/kg per day ( Arm 3 ; n=304 ) all with mycophenolate mofetil and corticosteroids ( tapered ) over 24 weeks , or tacrolimus QD 0.2 mg/kg per day with mycophenolate mofetil , basiliximab , and corticosteroids given only perioperatively ( Arm 4 ; n=283 ) . The primary composite endpoint ( efficacy failure ; per protocol set ) was defined as graft loss , biopsy-confirmed acute rejection , or graft dysfunction at week 24 . Graft dysfunction was defined as estimated glomerular filtration rate Modification of Diet in Renal Disease-4 formula of less than 40 mL/min/1.73 m2 . The prespecified noninferiority margin was 12.5 % . Results The per protocol set included 976 patients : 237 , 263 , 246 , and 230 patients in Arms 1 to 4 , respectively . Noninferiority of the composite endpoint was demonstrated for Arm 2 versus Arm 1 ; Kaplan – Meier estimates of efficacy failure were 42.2 % and 40.6 % , respectively ( difference , −1.6 % ; 95 % confidence interval [ CI ] , −12.2 % to 9.0 % ) . Noninferiority to Arm 1 was not confirmed for Arm 3 ( difference , −3.5 % ; 95 % CI , −13.6 % to 6.6 % ) or Arm 4 ( difference , −7.1 % ; 95 % CI , −16.1 % to 1.9 % ) . Graft dysfunction ( estimated glomerular filtration rate < 40 mL/min/1.73 m2 ) was the main determinant of composite-endpoint efficacy failure across all arms . Conclusions In patients representative of the European kidney Output:	For induction therapy , no treatment appeared more effective than another in reducing graft loss or mortality . Compared with placebo/no induction , rATG and BAS appeared more effective in reducing biopsy-proven acute rejection ( BPAR ) and BAS appeared more effective at improving GRF . For maintenance therapy , no treatment was better for all outcomes and no treatment appeared most effective at reducing graft loss . BEL + MMF appeared more effective than TAC + MMF and SRL + MMF at reducing mortality . MMF + CSA ( ciclosporin ) , TAC + MMF , SRL + TAC , TAC + AZA ( azathioprine ) and EVL + CSA appeared more effective than CSA + AZA and EVL + MPS at reducing BPAR . SRL + AZA , TAC + AZA , TAC + MMF and BEL + MMF appeared to improve GRF compared with CSA + AZA and MMF + CSA . In the base-case deterministic and probabilistic analyses , BAS , MMF and TAC were predicted to be cost-effective at £ 20,000 and £ 30,000 per quality -adjusted life-year ( QALY ) . Only a regimen of BAS induction followed by maintenance with TAC and MMF is likely to be cost-effective at £ 20,000 - 30,000 per QALY .
MS212033	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVES Blood transfusion has been shown to have deleterious effect on lung cancer survival , but little data are available that assess whether leukocyte-depleted ( LD ) blood has a similar adverse effect . Our institution has been using LD red cells since 2001 . We sought to determine whether LD blood has an effect on survival after resection of early-stage lung cancer . METHODS From a prospect i ve data base , we evaluated all patients with pathologic stage I non-small cell lung cancer . Patients receiving LD blood were compared with those receiving no transfusion . Survival was estimated using the Kaplan-Meier method and compared using the log-rank test . Multivariate analysis by Cox regression was used to identify independent risk factors affecting survival . RESULTS From 2001 to 2009 , 361 patients were evaluated ; 63 received LD red cell cell transfusion and 298 received no transfusion . Median follow-up was 48 months . Disease-free survival ( P < .001 ) and overall survival ( P < .001 ) were worse in patients receiving LD blood . Stratifying for stage , disease-free survival continued to be worse with transfusion for stage IA ( P = .002 ) and IB ( P = .002 ) . Similarly , overall survival continued to be worse with transfusion for stage IA ( P < .001 ) and IB ( P < .001 ) . For disease-free and overall survival , univariate analysis revealed increased age , male gender , anemia , transfusion , and higher stage to be adverse factors , with transfusion and higher stage continuing to be significant adverse factors after multivariate analysis . CONCLUSIONS Our data suggest that transfusion of LD blood is associated with a worse disease-free and overall survival in patients with resected stage I non-small cell lung cancer Background Little is known about prognosis of metastatic patients after receiving a first-line treatment and failure . Our group already showed in pre-treated patients enrolled in phase I clinical trials that a performance status ( PS ) > 2 and an LDH > 600 UI/L were independent prognostic factors . In this prospect i ve study , which included 45 patients , we identified clinical and biological variables as outcome predictors in metastatic Non-Small Cell lung cancer after first line chemotherapy were identified . Findings Forty-five patients that were previously treated for metastatic disease from 12/2000 to 11/2005 in the comprehensive cancer centre ( Centre Léon Bérard ) . Clinical assessment and blood parameters were recorded and considered . Patient prognostic factors for overall survival ( OS ) with a 0.05- significance level in univariate analysis were entered in a multivariate Cox model for further analysis . Patients ' median age was 58.5 years ( range : 37 - 76 ) . Sixty two percent of the patients were PS = 0 or 1 . After inclusion , nine patients received second-line ( 22.5 % ) , and two received third-line chemotherapy ( 5 % ) . Univariate analysis showed that the factors associated with reduced OS were : PS > 2 , weight loss > 10 % , more than one line of chemotherapy treatment and abnormal blood parameters ( hemoglobin ( Hb ) , platelet and neutrophils counts ) . Multiple regression analysis confirmed that PS > 2 and abnormal hemoglobin were independent predictors for low overall survival . According to the presence of none ( 33 % ) , 1 ( 37 % ) and 2 ( 30 % ) prognostic factors , median OS were 12 , 5 and 2 months respectively . Conclusion From this prospect i ve study , both PS and anemia were found as independent determinants of survival , we found that both PS and anemia were independent determinants of survival . The combination of poor PS and anemia is an effective strategy to predict survival in the case of patients with metastatic NSCLC receiving further treatment after the first line Purpose To evaluate the efficacy of concurrent radiochemotherapy in patients with stage III non-small cell lung cancer ( NSCLC ) , and to examine the effect of hemoglobin levels on survival of those patients . The negative impact of anemia on survival has been noticed for other cancer sites including the head and neck , and the uterine cervix , but it has been rarely described in NSCLC cancer patients treated with radiotherapy . Methods From April 1995 through March 2002 , 56 patients with inoperable stage III non-small lung cancer were treated with radiotherapy consisting of 60 Gy ( 50 Gy+10 Gy boost ) given in 30 fractions of 2 Gy daily , 5 days a week , over a period of 6 weeks , and concurrent low-dose daily chemotherapy ( CHT ) consisting of 6 mg/m2 of cisplatin given Mondays – Fridays during weeks 1–2 and 5–6 . All patients had stage III disease and ages ranged from 39 to 81 years old ( median 63.9 years ) . Results The 2-year and 3-year survival rates were 34 % and 16 % , respectively . Patients with a pretreatment hemoglobin level superior or equal to 11.6 g/dl had a 2-year survival rate of 52 % as compared to 15.5 % for patients with a pretreatment hemoglobin level inferior to 11.6 g/dl ( p=0.0075 ) . Patients with higher KI ( > 70 % ) showed better survival rates than those with lower KI . Surprisingly , patients in stage IIIA did not survive significantly longer than those in stage IIIB . Hematological toxicity ( grade ≥2 ) prevailed ( 25 % ) , followed by esophageal ( 5.4 % ) and bronchopulmonary ( 2 % ) toxicity . Only three patients experienced acute grade 3 hematological toxicity . Because of acute toxic effects , irradiation was interrupted in 8 patients ( 14.3 % ) for 7–13 days ( median 7.5 days ) . Late high- grade ( ≥3 ) toxicity was not found . No grade 4 toxicity or treatment-related deaths were observed during this study . Conclusion Our data show that concurrent radiotherapy with daily low dose cisplatin is well tolerated , and shows survival rates comparable to more aggressive treatment regimens . A combination of this chemotherapy with accelerated hyperfractionated radiotherapy might improve the results in the future . Furthermore , we could show that the hemoglobin levels prior to therapy have an influence on the prognosis , where lower levels were associated with worse outcome . Further trials should consider supplementation with erythropoietin BACKGROUND : According to the literature , performance status , stage-tumor dimension and nodal status , weight loss , were the most important prognostic factors for survival in patients with locally advanced non-small cell lung cancer . AIM : To evaluate the treatment results and the prognostic variables in our patients treated with sequential and concurrent chemoradiotherapy . MATERIAL AND METHODS : In the study 85 patients were r and omly assigned to one of the two treatment arms . In the sequential arm , 45 patients had previously received sequential chemotherapy with 4 cycles of and etoposide followed by conformal radiotherapy ( RT ) . In the second concurrent group , 40 patients received concomitant chemotherapy of cisplatine and etoposide and conformal RT , followed by two cycles of consolidation chemotherapy of carboplatine and etoposide . We described all phases of the conformal three dimensional ( 3-D ) RT . RESULTS : From October 2005 to March 2008 , 93 patients were enrolled . Eight patients were not eligible , seven had stage IV and one patient had pleural effusion . They were all initially considered to have stage IIIB disease . The median survival was 13 months for the patients in the sequential arm and 19 months for those in the concurrent treatment arm . The differences were statistically significant ( log-rank test p=0.0039 ) . The disease-free survival was 9 months in the sequential arm and 16 months in the concurrent treatment group . The differences were statistically significant ( log-rank test p=0.0023 ) . We found that the following prognostic factors significantly influenced the survival in lung cancer patients treated with conservative method : - age , p<0.05 ; - performant status , p<0.001 ; - weight loss , p<0.001 ; tumor dimension , p<0.05 ; and - nodal involvement , p<0.05 . CONCLUSION : In our study , the dose-limiting toxicity , esophagitis was reduced by performing conformal radiotherapy . Conformal thoracic radiotherapy and new radiotherapy technics , such as respiratory gated radiotherapy , allow dose escalating and may probably improve survival and local control in lung cancer patients Introduction : BR.21 demonstrated significant survival benefit for non-small cell lung cancer patients receiving erlotinib compared with placebo . We undertook to characterize , by exploratory subset analysis , patients less likely to benefit from erlotinib . Methods : Using stratification and potential prognostic factors , Cox regression with stepwise selection with minimum Akaike Information Criteria was used to separate erlotinib patients into risk categories based on 10th , 50th , and 90th percentiles of prognostic index scores . The hypothesis was that characteristics of treated patients in the highest risk group would be predictive of lack of benefit from erlotinib when comparing erlotinib to placebo patients in the same risk group . Results : Ten factors ( smoking history , performance status , weight loss , anemia , lactic dehydrogenase , response to prior chemotherapy , time from diagnosis , number of prior regimens , epidermal growth factor receptor copy , and ethnicity ) were predictive of overall survival for erlotinib-treated patients and were used in the final model . Four risk groups were derived from the index score of the Prognostic Model : Low Risk ( HR = 0.34 , p < 0.001 ) , Intermediate Low and Intermediate High Risk ( HR 0.76 , p = 0.05 ; HR 0.92 ; p = 0.51 ) and High Risk ( HR 1.07 ; p = 0.78 ) . Median survivals for erlotinib ( placebo ) patients in each group were 20.6 ( 8.9 ) , 10.4 ( 7.6 ) , 4.0 ( 4.1 ) , 1.9 ( 2.3 ) months . The trend test showed that higher risk was associated with shorter survival ( p < 0.001 ) and less treatment effect ( p = 0.03 ) . Conclusions : By establishing a prognostic model , we identified a small group of patients who did not seem to benefit from erlotinib in this study . This model requires prospect i ve validation to confirm that it is both prognostic and predictive of outcome We have evaluated the prognostic value of 22 pretreatment attributes in 436 small cell lung cancer ( SCLC ) patients included in a prospect i ve multicenter study with a minimum 5-year follow-up . Pretreatment clinical and laboratory parameters were registered . Possible prognostic factors were evaluated by univariate analysis ( log rank test ) and by the Cox multivariate regression model . In the univariate analysis of all patients , only age , nodal metastasis , and skin metastasis were not associated with survival . The multivariate Cox model identified gender , extent of disease , performance status ( PS ) , weight loss , platelet count , LDH , and NSE as independent prognostic factors . In subset multivariate analyses according to extent of disease , we found haemoglobin level , PS , NSE , and total WBC as significant prognostic indicators for survival in limited-stage disease ( LD-SCLC ) , while PS , weight loss , LDH , number of metastases , liver metastases , and brain metastases were identified as independent prognostic factors in extensive-stage disease ( ED-SCLC ) . There was a significant correlation between serum LDH and NSE levels . In conclusion , gender , extent of disease , PS , weight loss , haemoglobin , WBC count , platelet count , LDH , and NSE were all found to be independent prognostic factors for SCLC survival . However , the prognostic value of these factors depends highly on whether all or subsets of SCLC patients are studied PURPOSE The aim of this study was to analyze prognostic variables associated with long-term survival in patients with stage III non-small-cell lung cancer enrolled in a Spanish Lung Cancer Group ( SLCG ) phase II trial . PATIENTS AND METHODS Between May 2001 and June 2006 , 139 patients were enrolled . The initial design included 3 arms : sequential chemotherapy ( CT ) followed by st and ard thoracic radiation therapy ( TRT ; RT ) , concomitant CT/TRT followed by consolidation CT , or induction CT followed by CT/TRT . Based on the results of the Radiation Therapy Oncology Group 9410 trial , the sequential arm was closed . Induction or consolidation therapy comprised docetaxel plus gemcitabine . Concomitant treatment comprised docetaxel plus carboplatin plus 60 Gy TRT . A univariate and a Cox proportional hazard regression analysis of the following 11 variables were performed : age , sex , Eastern Cooperative Oncology Group performance status ( PS ) , histology , forced expiratory volume in 1 second , disease stage , nodal status , hemoglobin level , completion of RT treatment , completion of induction or consolidation plus concomitant treatment , and RT delay . RESULTS With a median follow-up of 23 months for living patients , median survival was 13.07 months for the consolidation arm and 14.65 months for the induction arm . The 4-year survival rates were 25.37 % and 32.35 % , respectively . Only RT treatment completion ( P < .0001 ) and induction or consolidation plus concomitant treatment completion ( P < .0001 ) were Output:	Conclusion A decreased pretreatment haemoglobin level among patients with lung cancer is a prognostic factor of poor survival that can serve as an important indicator in survival prediction , risk stratification and treatment selection .
MS212034	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background The effectiveness of bracing patients with IS has not yet been convincingly established due to a lack of RCTs . Some authors suggest that their results confirm that bracing is effective ; others conclude that the effectiveness of bracing is doubtful or recommend a RCT . The aim of this study was to establish whether bracing patients with idiopathic scoliosis ( IS ) in an early stage will result in at least 5 degrees less mean progression of the curvature compared to the control group after two years of follow-up . Methods A r and omized controlled trial was design ed . Eligible patients are girls and boys in the age group 8–15 years whose diagnosis of IS has been established by an orthopedic surgeon , who have not yet been treated by bracing or surgery , and for whom further growth of physical height is still expected based on medical examination and maturation characteristics ( Risser ≤ 2 ) . The Cobb angle of the eligible patient should either be minimally 22 and maximally 29 degrees with established progression of more than 5 degrees , or should be minimally 30 and maximally 35 degrees ; established progression for the latter is not necessary . A total of 100 patients will be included in this trial . The intervention group will be treated with full-time Boston brace wear ; the control group will not be braced . Every four months , each patient will have a physical and an X-ray examination . The main outcomes will be the Cobb angle two years after inclusion and health-related quality of life . Discussion The results of this trial will be of great importance for the discussion on early treatment for scoliosis . Furthermore , the result will also be important for screening for scoliosis policies . Trial registration Nederl and s Trialregister IS RCT Study Design . A consecutive series of female patients with adolescent idiopathic scoliosis treated between 1968 and 1977 , either with distraction and fusion using Harrington rods ( n = 145 ) or with a brace ( n = 122 ) , were followed for at least 20 years after completion of the treatment . Objectives . To determine the long-term outcomes of childbearing and sexual life in women treated for adolescent idiopathic scoliosis , as compared with matched control subjects who did not have scoliosis . Summary of Background Data . The effect of pregnancy on curve progression is not established , and results are contradictory . Few reports exist on the social life ( marriage , childbearing , and sexual function ) of formerly treated individuals with scoliosis . Methods . In this study , 136 surgically treated women ( 94 % ) and 111 brace-treated women ( 91 % ) completed the Scoliosis Research Society (SRS)/MODEM ’s question naire concerning childbearing and sexual life as a part of an unbiased personal follow-up examination . Of these , 129 surgically treated and 105 brace-treated women also underwent a radiographic examination . The Cobb method was used to measure curve size in present and earlier examinations . An age-matched control group of 90 women was r and omly selected and subjected to the same examinations . Results . The mean age for all the groups was 40 years . Of the surgically treated and brace-treated women , 85 % were or had been married , as compared with 82 % of the control women . In the total cohort , 628 pregnancies had occurred . No significant mean difference existed between the groups in the number of children born ( 1.8 for the surgically treated , 1.9 for the brace-treated , and 2 for the control women ) ( P = 0.25 ) . The patients in the brace-treated group had a significantly higher mean age at first pregnancy ( 28 years ) than the control subjects ( 25.9 years ) ( P = 0.011 ) , whereas the age for the surgically treated women ( 26.6 years ) did not differ significantly from that for the brace-treated women . There were no significant differences between the groups in rates for low back pain ( 35 % for the surgically treated , 43 % for the brace-treated , and 28 % for the control group ) or for cesarean section ( 19 % for the surgically treated , 14 % for the brace-treated , and 18 % for the control group ) during the first pregnancy . The rate of vacuum extraction s was higher in the surgically treated group ( 16 % ) than in thecontrol group ( 5 % ) ( P = 0.036 ) or the brace-treated group(8 % ) . Limitation of sexual function from the back was admitted by 33 % of the surgically treated , 28 % of the brace-treated , and 15 % of the control women : surgically treated vs control subjects ( P = 0.0042 ) , brace-treated vs control subjects ( P = 0.026 ) , and brace-treated vs surgically treated subjects ( P = 0.57 , a nonsignificant difference ) . These limitations were largely because of difficulties participating physically in activities or self-consciousness about appearance . Pain was a minor reason for limitation . There was no correlation between progression of the major or lumbar curve and number of pregnancies , or between curve progression and age at first pregnancy . Conclusions . Patients treated for adolescent idiopathic scoliosis appeared to function well with regard to marital status and number of children . The scoliotic curve did not seem to increase as a result of childbearing . Minor problems occurred during pregnancy and delivery . Some patients , however , experienced a slight negative effect in their sexual life Abstract In a 5-year prospect i ve study on idiopathic scoliosis , an attempt was made to eluci date the natural history of the disease and to determine which factors contribute to curve progression . A total of 85,622 children were examined for scoliosis in a prospect i ve school screening study carried out in northwestern and central Greece . Curve progression was studied in 839 of the 1,436 children with idiopathic scoliosis of at least 10 ° detected from the school screening program . Each child was followed clinical ly and roentgenographically for one to four follow-up visits for a mean of 3.2 years . Progression of the scoliotic curve was recorded in 14.7 % of the children . Spontaneous improvement of at least 5 ° was observed in 27.4 % of them , with 80 children ( 9.5 % ) demonstrating complete spontaneous resolution . Eighteen percent of the patients remained stable , while the remaining patients demonstrated nonsignificant changes of less than 5 ° in curve magnitude . A strong association was observed between the incidence of progression and the sex of the child , curve pattern , maturity , and to a lesser extent age and curve magnitude . More specifically , the following were associated with a high risk of curve progression : sex ( girls ) ; curve pattern ( right thoracic and double curves in girls , and right lumbar curves in boys ) ; maturity ( girls before the onset of menses ) ; age ( time of pubertal growth spurt ) ; and curve magnitude ( ≥ 30 ° ) . On the other h and , left thoracic curves showed a weak tendency for progression . In conclusion , the findings of the present study strongly suggest that only a small percentage of scoliotic curves will undergo progression . The pattern of the curve according to curve direction and sex of the child was found to be a key indicator of which curves will progress BACKGROUND CONTEXT The value of scoliosis screening has been recently shown in a multicenter r and omized controlled trial . However , the long-term sustainability of the clinical effectiveness of scoliosis screening as a routine health service remains unknown . PURPOSE The aim of this study was to assess the sustainability of the clinical effectiveness of school scoliosis screening . STUDY DESIGN / SETTING A large population -based cohort study with a 10-year follow-up was conducted . PATIENT SAMPLE A total of 394,401 students who were in the fifth grade during the five academic years from 1995/1996 to 1999/2000 formed five consecutive annual cohorts . The students were eligible for the Hong Kong scoliosis screening program , with their screening history and medical records until their nineteenth birthdays being assessed . OUTCOME MEASURES The outcome measures considered in the study were development of adolescent idiopathic scoliosis by the 19 years of age and the Cobb angle . METHODS The clinical effectiveness of scoliosis screening was assessed by referral rate for radiographic diagnosis , sensitivity , specificity , and predictive values . RESULTS A total of 306,144 students ( 78 % ) participated in scoliosis screening , which used a two-tier system . The prevalence of curves of 20 ° or greater was 1.8 % ( 95 % confidence interval [ CI ] , 1.7 - 1.8 % ) , whereas the referral rate for radiography , the sensitivity , and the positive predictive value ( PPV ) for curves of 20 ° or greater were 4.1 % ( 95 % CI , 4.0 - 4.2 % ) , 91 % ( 95 % CI , 90 - 92 % ) , and 40 % ( 95 % CI , 39 - 41 % ) , respectively . Across the five consecutive annual cohorts , the prevalence and sensitivity for curves of 20 ° or greater increased by 0.23 % ( 95 % CI , 0.21 - 0.25 % ; p<.001 ) and 0.76 % ( 95 % CI , 0.43 - 1.04 % ; p<.001 ) per year , respectively ; however , the PPV was reduced by 1.71 % ( 95 % CI , 1.09 - 2.33 % ; p<.001 ) per year . CONCLUSIONS This report describes the first large population -based study with a long-term follow-up indicating that a scoliosis screening program can have sustained clinical effectiveness in identifying patients with adolescent idiopathic scoliosis needing clinical observation . As the prevalence of adolescent idiopathic scoliosis increases , scoliosis screening should be continued as a routine health service in schools or by general practitioners if there is no scoliosis screening policy Abstract . No results on long-term outcome in terms of health-related quality of life ( HRQL ) have previously been presented for patients treated for adolescent idiopathic scoliosis . A consecutive series of patients with adolescent idiopathic scoliosis , treated between 1968 and 1977 before the age of 21 , either with distraction and fusion using Harrington rods [ surgical treatment group ( ST ) , n=156 ; 145 females and 11 males ] or with a brace [ brace treatment group ( BT ) , n=127 ; 122 females and 5 males ] were followed at least 20 years after completion of the treatment . Ninety-four percent of ST and 91 % of BT patients filled in a question naire comprising the SF-36 , Psychological General Well-Being Index ( PGWB ) , Oswestry Disability Back Pain Question naire , parts of SRS/MODEM 'S question naire and study -specific questions concerning the treatment , as a part of an unbiased personal follow-up examination including radiography and clinical examination . An age- and sex-matched control group of 100 persons was r and omly selected and subjected to the same examinations . The results showed no differences in terms of sociodemographic data between the groups . Both ST and BT patients had a slightly , but significantly , reduced physical function using the SF-36 subscales , SF-36/Physical Component Summary ( PCS ) score as well as the Oswestry Disability Back Pain Question naire compared to the controls . Neither the mental subscales and the Mental Component Summary ( MCS ) score of SF-36 nor the PGWB index showed any significant difference between the groups . Forty-nine percent of ST , 34 % of BT and 15 % of controls admitted limitation of social activities due to their back [ P<0.001 ST vs controls , P=0.0010 BT vs controls , and n.s . ( P=0.024 ) ST vs BT ] , mostly due to difficulties with physical participation in activities or self-consciousness about appearance . Pain was a minor reason for limitation . No correlation was found between the outcome scores and curve size after treatment , curve type , total treatment time or age at completed treatment . Patients treated for adolescent idiopathic scoliosis were found to have approximately the same HRQL as the general population . A minority of the patients ( 4 % ) had a severely decreased psychological well-being , and a few ( 1.5 % ) were severely physically disabled due to the back In a study conducted by the Scoliosis Research Society , 159 girls with a mean age of thirteen years ( range , ten to fifteen years ) who had adolescent idiopathic scoliosis were followed prospect ively until skeletal maturity or until the curve had increased 6 degrees or more . All patients had had an initial curve of 25 to 35 degrees and an apical level between the eighth thoracic and first lumbar vertebrae , inclusive . Of the 159 patients , 120 were observed without treatment and thirty-nine were managed with lateral electrical surface stimulation . The curve progressed at least 6 degrees in eighty patients . There was no apparent difference in the outcome between the patients who were managed with observation only and those who were given electrical stimulation . Logistic regression analysis was performed to determine which of eleven factors were predictive of progression of the scoliotic curve . A Risser sign of 0 or 1 , an apical level cephalad to the twelfth thoracic vertebra , and an imbalance of ten millimeters or less were found to be independently prognostic of progression of more than 6 degrees . A prognostic model that included these three factors and chronological age allowed correct classification of the curve as either progressive or non-progressive in 81 per cent of these patients who had a thoracic or thoracol Output:	There was no evidence on the effect of AIS screening on adult health outcomes . Conclusions and Relevance Screening can detect AIS . Bracing and possibly exercise treatment can interrupt or slow progression of curvature in adolescence . However , there is little or no evidence on long-term outcomes for AIS treated in adolescence , the association between curvature at skeletal maturity and adult health outcomes , the harms of AIS screening or treatment , or the effect of AIS screening on adult health outcomes
MS212035	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: This open-label , phase 1 study evaluated the effects of ofatumumab on QTc intervals , safety , efficacy , B-cell and neutrophil counts , complement levels , and cytokine and chemokine concentrations . Fourteen patients with fludarabine-refractory chronic lymphocytic leukemia received 12 ofatumumab infusions . A higher maximum infusion rate of 400 mL/h was tested at the first two doses and was well tolerated . The 43 % overall response rate was similar to previous data ( 42–51 % ) . B-cell depletion was observed along with complement consumption ; median C2 and CH50 levels appeared lower during monthly dosing in patients who responded . Responding patients appeared to have higher median levels of certain pro-inflammatory cytokines and lower median levels of certain immunotolerant cytokines than patients who did not respond . Ofatumumab-induced complement-dependent cytotoxicity activity can be detected clinical ly by measuring complement and may be associated with clinical activity . The potential relationship between changes in complement or cytokines and clinical response to ofatumumab warrants further study We report the largest retrospective , phase IV non-interventional , observational study of ofatumumab therapy in heavily pre-treated patients with poor-prognosis chronic lymphocytic leukemia . Total number of patients was 103 ; median age was 65 years ( range 39–85 ) . Median number of prior lines of therapy was 4 ( range 1–13 ) , including , in most cases , rituximab- , fludarabine- and alemtuzumab-based regimens ; 13 patients had been allografted . Of 113 adverse events , 28 ( 29 % ) were considered to be directly related to ofatumumab . Grade 3–4 toxicities included neutropenia ( 10 % ) , thrombocytopenia ( 5 % ) , anemia ( 3 % ) , pneumonia ( 17 % ) , and fever ( 3 % ) . Two heavily pre-treated patients developed progressive multifocal leukoencephalopathy . On an intention-to-treat analysis , the overall response rate was 22 % ( 3 complete response , 1 incomplete complete response ) . Median progression-free and overall survival times were 5 and 11 months , respectively . This study confirms in a daily-life setting the feasibility and acceptable toxicity of ofatumumab treatment in advanced chronic lymphocytic leukemia . The complete response rate , however , was low . Therefore , treatment with ofatumumab should be moved to earlier phases of the disease . Ideally , this should be done in combination with other agents , as recently approved for ofatumumab plus chlorambucil as front-line treatment for patients unfit for fludarabine . This study is registered at clinical trials.gov identifier:01453062 There are limited data on retreatment with monoclonal antibodies ( mAb ) in patients with chronic lymphocytic leukaemia ( CLL ) . In a pivotal study , ofatumumab ( human anti‐CD20 mAb ) monotherapy demonstrated a 47 % objective response rate ( ORR ) in fludarabine refractory CLL patients . From this study , a subset of 29 patients who had at least stable disease and then progressed were retreated with eight weekly ofatumumab infusions ( induction treatment period ) , followed by monthly infusions for up to 2 years ( maintenance treatment period ) . The ORR after 8 weeks of induction retreatment was 45 % and 24 % had continued disease control after maintenance at 52 weeks . Efficacy and safety of the retreated patients were compared with their initial results in the pivotal study . Response duration was 24·1 months vs. 6·8 months ; time to next therapy was 14·8 months vs. 12·3 months ; and progression‐free survival was 7·4 months vs. 7·9 months ( medians ) . Upon retreatment , 72 % had infusion reactions , mostly Grade 1–2 . Three patients had fatal infections . In summary , ofatumumab retreatment and maintenance therapy was feasible in patients with heavily pretreated CLL and appeared to result in more durable disease control than initial ofatumumab treatment in this subset of patients who may have a more favourable disease profile Objectives Ofatumumab is a human IgG1κ monoclonal antibody that targets a membrane proximal epitope encompassing the small and large loops of CD20 . This Phase I study evaluated the safety , tolerability , efficacy and pharmacokinetics of ofatumumab monotherapy in Japanese patients with relapsed/refractory B-cell chronic lymphocytic leukemia and small lymphocytic lymphoma . Methods Ofatumumab was administered intravenously weekly for a total of eight doses ( dose escalation : 500 and 1000 mg ) . Six patients ( two chronic lymphocytic leukemia and four small lymphocytic lymphoma ) were enrolled into two dose cohorts ( 500 mg , three patients ; 1000 mg , three patients ) . All six patients received 300 mg ofatumumab at the first infusion and either 500 or 1000 mg at seven subsequent weekly infusions . Results No dose-limiting toxicities or serious adverse events were observed . Grade 3–4 adverse events observed were grade 3 lymphocytopenia ( n = 1 ) and neutropenia ( n = 1 ) . Grade 1–2 infusion-related adverse events leading to temporary interruption of ofatumumab infusion were observed in all six patients on the first infusion day , and all patients completed the planned eight infusions . The overall response rate was 50 % ( 3/6 ) . Conclusions Ofatumumab was well tolerated at doses up to 1000 mg and showed preliminary evidence of activity in relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma , warranting further investigations . This study was registered at Clinical Trials.gov ( NCT00742144 ) Despite the recent advances in treatment of CLL with targeted agents such as ibrutinib , availability of nonchemotherapy based therapies is desired . Given the 58 % response rate ( 1996 NCI‐WG criteria ) of single agent ofatumumab in CLL refractory to fludarabine and alemtuzumab , we initiated a phase II trial examining response , safety , and progression‐free survival ( PFS ) of ofatumumab as front‐line monotherapy . Patients enrolled included untreated , symptomatic CLL patients over the age of 65 or those who were inappropriate/did not desire chemotherapy . Two cohorts were enrolled sequentially examining either 1 g ( 33 patients ) or 2 g ( 44 patients ) weekly for 8 weeks followed by maintenance dosing every 2 months for a total of 24 months . Patients receiving 1 g were older than those receiving 2 g , but there were no significant differences in other clinical characteristics . The best overall response rates in the 1 and 2 g patient cohorts were 72 and 89 % ( 1996 NCI‐WG criteria ) , respectively ( 54 and 68 % , respectively , using 2008 IWCLL criteria ) . All but two responses were partial . The 24‐month estimated PFS rates were 46 and 78 % , respectively . Response and PFS was lower in del(17p ) and del(11q ) CLL patients . Differences in PFS between dose cohorts were statistically significant and remained so when adjusting for age or high‐risk cytogenetics . Toxicity of this treatment was mild with only six patients not completing therapy due to toxicity . Ofatumumab induction followed by maintenance therapy in untreated CLL represents a well‐tolerated and active regimen , particularly with the 2 g of ofatumumab . Am . J. Hematol . 91:1020–1025 , 2016 . © 2016 Wiley Periodicals , Safety and efficacy of the fully human anti-CD20 monoclonal antibody , ofatumumab , was analyzed in a multicenter dose-escalating study including 33 patients with relapsed or refractory chronic lymphocytic leukemia . Three cohorts of 3 ( A ) , 3 ( B ) , and 27 ( C ) patients received 4 , once weekly , infusions of ofatumumab at the following doses : ( A ) one 100 mg and three 500 mg ; ( B ) one 300 mg and three 1000 mg ; ( C ) one 500 mg and three 2000 mg . Sixty-seven percent of the patients were Binet stage B , and the median number of previous treatments was 3 . The maximum tolerated dose was not reached . The majority of related adverse events occurred at first infusion , and the number of adverse events decreased at each subsequent infusion . Seventeen ( 51 % ) of 33 patients experienced infections , 88 % of them of grade 1 - 2 . One event of interstitial pneumonia was fatal ; all other cases resolved within one month . The response rate of cohort C was 50 % ( 13/26 ) , one patient having a nodular partial remission and 12 patients partial remission . In conclusion , ofatumumab was found to be well tolerated in patients with chronic lymphocytic leukemia ( CLL ) in doses up to 2000 mg . Preliminary data on safety and objective response are encouraging and support further studies on the role of ofatumumab in CLL patients . This trial was registered at www . clinical trials.gov as no. NCT00093314 PURPOSE New treatments are needed for patients with fludarabine- and alemtuzumab-refractory ( FA-ref ) chronic lymphocytic leukemia ( CLL ) or patients with fludarabine-refractory CLL with bulky ( > 5 cm ) lymphadenopathy ( BF-ref ) who are less suitable for alemtuzumab treatment ; these groups have poor outcomes with available salvage regimens . Ofatumumab ( HuMax-CD20 ) is a human monoclonal antibody targeting a distinct small-loop epitope on the CD20 molecule . We conducted an international clinical study to evaluate the efficacy and safety of ofatumumab in patients with FA-ref and BF-ref CLL . PATIENTS AND METHODS Patients received eight weekly infusions of ofatumumab followed by four monthly infusions during a 24-week period ( dose 1 = 300 mg ; doses 2 to 12 = 2,000 mg ) ; response by an independent review committee ( 1996 National Cancer Institute Working Group criteria ) was assessed every 4 weeks until week 24 and then every 3 months until month 24 . RESULTS This planned interim analysis included 138 treated patients with FA-ref ( n = 59 ) and BF-ref ( n = 79 ) CLL . The overall response rates ( primary end point ) were 58 % [ corrected ] and 47 % in the FA-ref and BF-ref groups , respectively . Complete resolution of constitutional symptoms and improved performance status occurred in 57 % and 48 % of patients , respectively . Median progression-free survival and overall survival times were 5.7 and 13.7 months in the FA-ref group , respectively , and 5.9 and 15.4 months in the BF-ref group , respectively . The most common adverse events during treatment were infusion reactions and infections , which were primarily grade 1 or 2 events . Hematologic events during treatment included anemia and neutropenia . CONCLUSION Ofatumumab is an active , well-tolerated treatment providing clear clinical improvements for fludarabine-refractory patients with very poor-prognosis CLL BACKGROUND Ofatumumab is a human anti-CD20 monoclonal antibody that has proven efficacy as monotherapy in refractory chronic lymphocytic leukaemia . We assessed the efficacy and safety of ofatumumab maintenance treatment versus observation for patients in remission after re-induction treatment for relapsed chronic lymphocytic leukaemia . METHODS This open-label , multicentre , r and omised phase 3 study enrolled patients aged 18 years or older from 130 centres in 24 countries who had chronic lymphocytic leukaemia in complete or partial remission after second-line or third-line treatment . Eligible patients had a WHO performance status of 0 - 2 , had a response assessment within the previous 3 months , did not have refractory disease , autoimmune haemolytic anaemia requiring treatment , chronic or active infection requiring treatment , and had not previously received maintenance treatment or autologous or allogeneic stem-cell transplant . Using a r and omisation list generated by a central computerised system and an interactive voice recognition system , we r and omly assigned ( 1:1 ) patients to receive ofatumumab ( 300 mg followed by 1000 mg 1 week later and every 8 weeks for up to 2 years ) or undergo observation . R and omisation was stratified by number and type of previous treatment and remission status after induction treatment ( block size of four ) . Treatment assignment was open label . The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population . We report the results of a prespecified interim analysis after two-thirds of the planned study events ( disease progression or death ) had happened . This trial is closed to accrual but follow-up is ongoing . This trial is registered with Clinical Trials.gov , number NCT00802737 . FINDINGS Between May 6 , 2010 , and June 19 , Output:	The pooled toxicity analysis showed that Ofatumumab-based therapy was associated with an increased risk of infusion-related reaction but decreased risk of thrombocytopenia and anemia compared with non-Ofatumumab-based therapy . Moreover , infections , and infusion-related reaction occurred more frequently in participants with single Ofatumumab studies . Discussion : Our analysis showed PFS was statistically significantly improved with Ofatumumab-based treatments ( including Ofatumumab alone , Ofatumumab plus chemotherapy ) for CLL compared with observation or chemotherapy-based regimen groups . Ofatumumab had no statistically significant improvement on the OS of patients with CLL . The Ofatumumab-based therapy could generally decrease the risk of adverse effects except infusion-related reaction and infections
MS212036	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Hypercholesterolemia is a major risk factor for cardiovascular disease . Not all patients respond well to traditional cholesterol lowering medications . Probiotics have been evaluated for their cholesterol-lowering effects in humans with variable results . This study was performed to evaluate the efficacy of two probiotics in lowering the serum cholesterol of hypercholesterolemic patients . MATERIAL S AND METHODS A r and omized double-blind controlled trial was conducted comparing placebo to Lactobacillus acidophilus plus Bifidobacterium bifidum in patients diagnosed with hypercholesterolemia . Placebo or probiotic capsules were taken three times daily for six weeks . Pre- and post-treatment total cholesterol ( TC ) , HDL-cholesterol ( HDL-C ) , LDL-cholesterol ( LDL-C ) and triglyceride ( TG ) levels and demographic parameters of the two groups were compared . From a total of 70 participants , 64 completed the assigned treatment ( 31 in probiotics group and 33 in the control group).The two treatment groups were matched for age , sex , weight , height , BMI , waist and hip circumferences , and blood pressure . RESULTS Baseline evaluation revealed no difference between the probiotics group and control group levels of TC , HDL-C , LDL-C and TG . TC levels in the probiotics group decreased during treatment ( 237.2 vs. 212.7 mg/dL , p<0.05 ) . TC and LDL-C levels in the control group increased significantly from their baseline levels during treatment . TC ( 212.7 vs 252.8 mg/dL , p<0.001 ) , HDL-C ( 52.0 vs 59.1 mg/dL , p=0.04 ) and LDL-C ( 153.9 vs 182.1 mg/dL , p<0.01 ) levels in the probiotics group were significantly lower at the end of treatment than the corresponding levels in the control group . CONCLUSION A combination of Lactobacillus acidophilus and Bifidobacterium bifidum decreased serum total cholesterol , LDL-cholesterol and HDL-cholesterol levels in hypercholesterolemic patients over a six week period . There was no effect on serum triglyceride or fasting blood glucose levels BACKGROUND The short-chain fatty acids formed in the human colon by the bacterial fermentation of fiber may have an antiinflammatory effect , may reduce insulin production , and may improve lipid metabolism . We previously showed in hypercholesterolemic patients that supplementation with the probiotic bacteria Lactobacillus plantarum 299v significantly lowers concentrations of LDL cholesterol and fibrinogen . OBJECTIVE We determined the influence of a functional food product containing L. plantarum 299v on lipid profiles , inflammatory markers , and monocyte function in heavy smokers . DESIGN Thirty-six healthy volunteers ( 18 women and 18 men ) aged 35 - 45 y participated in a controlled , r and omized , double-blind trial . The experimental group drank 400 mL/d of a rose-hip drink containing L. plantarum 299v ( 5 x 10(7 ) colony-forming units/mL ) ; the control group consumed the same volume of product without bacteria . The experiment lasted 6 wk and entailed no changes in lifestyle . RESULTS Significant decreases in systolic blood pressure ( P < 0.000 ) , leptin ( P < 0.000 ) , and fibrinogen ( P < 0.001 ) were recorded in the experimental group . No such changes were observed in the control group . Decreases in F(2)-isoprostanes ( 37 % ) and interleukin 6 ( 42 % ) were also noted in the experimental group in comparison with baseline . Monocytes isolated from subjects treated with L. plantarum showed significantly reduced adhesion ( P < 0.001 ) to native and stimulated human umbilical vein endothelial cells . CONCLUSION L. plantarum administration leads to a reduction in cardiovascular disease risk factors and could be useful as a protective agent in the primary prevention of atherosclerosis in smokers Aim Evidence of a possible connection between gut microbiota and several physiological processes linked to type 2 diabetes is increasing . However , the effect of multi-strain probiotics in people with type 2 diabetes remains unclear . This study investigated the effect of multi-strain microbial cell preparation — also refers to multi-strain probiotics — on glycemic control and other diabetes-related outcomes in people with type 2 diabetes . Design A r and omized , double-blind , parallel-group , controlled clinical trial . Setting Diabetes clinic of a teaching hospital in Kuala Lumpur , Malaysia . Participants A total of 136 participants with type 2 diabetes , aged 30–70 years , were recruited and r and omly assigned to receive either probiotics ( n = 68 ) or placebo ( n = 68 ) for 12 weeks . Outcomes Primary outcomes were glycemic control-related parameters , and secondary outcomes were anthropomorphic variables , lipid profile , blood pressure and high-sensitivity C-reactive protein . The Lactobacillus and Bifidobacterium quantities were measured before and after intervention as an indicator of successful passage of the supplement through gastrointestinal tract . Statistical analysis Intention-to-treat ( ITT ) analysis was performed on all participants , while per- protocol ( PP ) analysis was performed on those participants who had successfully completed the trial with good compliance rate . Results With respect to primary outcomes , glycated hemoglobin decreased by 0.14 % in the probiotics and increased by 0.02 % in the placebo group in PP analysis ( p < 0.05 , small effect size of 0.050 ) , while these changes were not significant in ITT analysis . Fasting insulin increased by 1.8 µU/mL in placebo group and decreased by 2.9 µU/mL in probiotics group in PP analysis . These changes were significant between groups at both analyses ( p < 0.05 , medium effect size of 0.062 in PP analysis and small effect size of 0.033 in ITT analysis ) . Secondary outcomes did not change significantly . Probiotics successfully passed through the gastrointestinal tract . Conclusion Probiotics modestly improved HbA1c and fasting insulin in people with type 2 diabetes Background Gut lactobacilli can affect the metabolic functions of healthy humans . We tested whether a 1500 kcal/d diet supplemented with cheese containing the probiotic Lactobacillus plantarum TENSIA ( Deutsche Sammlung für Mikroorganismen , DSM 21380 ) could reduce some symptoms of metabolic syndrome in Russian adults with obesity and hypertension . Methods In this 3-week , r and omized , double-blind , placebo-controlled , parallel pilot study , 25 subjects ingested probiotic cheese and 15 ingested control cheese . Fifty grams of each cheese provided 175 kcal of energy . Blood pressure ( BP ) , anthropometric characteristics , markers of liver and kidney function , metabolic indices ( plasma glucose , lipids , and cholesterol ) , and urine polyamines were measured . Counts of fecal lactobacilli and L. plantarum TENSIA were evaluated using molecular methods . The data were analyzed by t-test for independent sample s and Spearman ’s partial correlation analysis . Results The probiotic L. plantarum TENSIA was present in variable amounts ( 529.6 ± 232.5 gene copies ) in 16/25 ( 64 % ) study subjects . Body mass index ( BMI ) was significantly reduced ( p = 0.031 ) in the probiotic cheese group versus the control cheese group . The changes in BMI were closely associated with the water content of the body ( r = 0.570 , p = 0.0007 ) when adjusted for sex and age . Higher values of intestinal lactobacilli after probiotic cheese consumption were associated with higher BMI ( r = 0.383 , p = 0.0305 ) and urinary putrescine content ( r = 0.475 , p = 0.006 ) . In patients simultaneously treated with BP-lowering drugs , similar reductions of BP were observed in both groups . A positive association was detected between TENSIA colonization and the extent of change of morning diastolic BP ( r = 0.617 , p = 0.0248 ) and a trend toward lower values of morning systolic BP ( r = −0.527 , p = 0.0640 ) at the end of the study after adjusting for BMI , age , and sex . Conclusion In a pilot study of obese hypertensive patients , a hypocaloric diet supplemented with a probiotic cheese helps to reduce BMI and arterial BP values , recognized symptoms of metabolic syndrome . Trial registration Current Controlled Trials IS RCT Objective : Two tripeptides ( Val-Pro-Pro and Ile-Pro-Pro ) that have inhibitory activities for angiotensin I-converting enzyme are produced in milk fermented with Lactobacillus helveticus . In this study we evaluated the effect and safety of powdered fermented milk with L. helveticus CM4 on subjects with high-normal blood pressure or mild hypertension . Methods : A r and omized , placebo-controlled , double-blind study was conducted using 40 subjects with high-normal blood pressure ( HN group ) and 40 subjects with mild hypertension ( MH group ) . Each subject ingested 6 test tablets ( 12 g ) containing powdered fermented milk with L. helveticus CM4 daily for 4 weeks ( test group ) or the same amount of placebo tablets for 4 weeks ( placebo group ) . Results : During treatment , the decrease in systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) in the test group tended to be greater than in the placebo group for both blood pressure groups . At the end of treatment ( week 4 ) , a significant decrease in DBP in the HN group was observed ( i.e. 5.0 mm Hg ( 0.1 , 9.9 ; p = 0.04 ) compared with the placebo group ) . There was no significant change in SBP ( 3.2 mm Hg ( 95 % CI −2.6 , 8.9 ; p = 0.27 ) . In the MH group , SBP decreased by 11.2 mm Hg ( 4.0 , 18.4 ; p = 0.003 ) and there was a statistically non-significant decrease in DBP of 6.5 mm Hg ( −0.1 , 13.0 ; p = 0.055 ) compared with the placebo group . No marked changes were observed in other indexes , including pulse rate , body weight and blood serum variables , and no adverse effects attributed to the treatment was found in each group . Conclusions : Daily ingestion of the tablets containing powdered fermented milk with L. helveticus CM4 in subjects with high-normal blood pressure or mild hypertension reduces elevated blood pressure without any adverse effects BACKGROUND AND AIMS Despite strong mechanistic data , and promising results from in vitro and animal studies , the ability of probiotic bacteria to improve blood pressure and serum lipid concentrations in humans remains uncertain . The aim of this study was to determine the effect of Lactobacillus acidophilus La5 and Bifidobacterium animalis subsp lactis Bb12 , provided in either yoghurt or capsule form , on home blood pressure and serum lipid profile . METHODS AND RESULTS Following a 3-week washout period , 156 overweight men and women over 55 y were r and omized to a 6-week double-blinded , factorial , parallel study . The four intervention groups were : A ) probiotic yoghurt plus probiotic capsules ; B ) probiotic yoghurt plus placebo capsules ; C ) control milk plus probiotic capsules ; and D ) control milk plus placebo capsules . Each probiotic test article provided a minimum L. acidophilus La5 and B. animalis subsp . lactis Bb12 dose of 3.0 × 10⁹ CFU/d . Home blood pressure monitoring , consisting of 7-day bi-daily repeat measurements , were collected at baseline and week 6 . Fasting total cholesterol , low density lipoprotein cholesterol ( LDLC ) , high density lipoprotein cholesterol ( HDLC ) , and serum triglyceride were performed at baseline and week 6 . When compared to control milk , probiotic yoghurt did not significantly alter blood pressure , heart rate or serum lipid concentrations ( P > 0.05 ) . Similarly , when compared to placebo capsules , supplementation with probiotic capsules did not alter blood pressure or concentrations of total cholesterol LDLC , HDLC , or triglycerides ( P > 0.05 ) . CONCLUSIONS The probiotic strains L. acidophilus La5 and B. animalis subsp . lactis Bb12 did not improve cardiovascular risk factors The blood pressure-lowering effect of dairy products holds the potential to decrease the risk of cardiovascular disease ( CVD ) . An open question is if the successful expression of functional properties of the probiotic strain depends on host biomarkers and /or food matrix properties . The probiotic Lactobacillus plantarum strain TENSIA ® ( DSM 21380 ) is a novel microorganism with Output:	Our meta- analysis showed a modest but a significant reduction in SBP and DBP in patients with hypertension , particularly in those with diabetes mellitus , following probiotic supplementation . This effect was associated with treatment duration , dosage , and the age of subject but was not associated with single or multiple strains usage . Additionally , probiotic supplement had a beneficial effect in reducing BMI and blood glucose
MS212037	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The treatment of patients with severe lupus nephritis remains controversial . Comparison of treatment outcomes from existing controlled trials is hampered by the heterogeneity of the patient groups with their different intrinsic disease progression . Corticosteroids with cyclophosphamide or azathioprine remain the mainstay of treatment , although meta- analysis has failed to show the superiority of cyclophosphamide over the less toxic azathioprine . The development of safer alternative treatments for the induction of remission of nephritis , long term maintenance , and the management of patient groups refractory to current therapies remains the goal . Mycophenolate mofetil ( MMF ) is one of a number of newer therapies , including ̄udarabine , CTLA4-Ig and anti-C5b under evaluation in lupus nephritis . MMF may potentially offer an alternative for the induction of remission , treatment of refractory , and maintenance of severe lupus nephritis . Controlled trials in renal transplantation have found that MMF reduces the incidence of acute rejection , and is superior to azathioprine when combined with cyclosporin and prednisolone for this indication . The role of MMF in chronic allograft nephropathy is less certain but recently retrospective analysis of data from the US Renal Transplant Registry has shown that MMF decreases the risk of developing chronic allograft failure . This was found to be partly due to MMF decreasing the incidence of acute rejection , but was also caused by an effect independent of acute rejection . The success of MMF in allotransplantation has led to its use in a number of autoimmune diseases and there have been published case series examining its use in Takaysau 's arteritis , refractory uveitis , psoriasis and Crohn 's disease . Recently , reports of MMF in lupus nephritis apparently refractory to cyclophosphamide have been published with encouraging results . The role of MMF for remission induction in severe biopsy proven lupus nephritis , in patients without previous cytotoxic exposure is the subject of several ongoing prospect i ve studies Controlled clinical trials in renal transplantation have demonstrated that mycophenolate mofetil is well tolerated and has lower renal transplant rejection rates than azathioprine regimens . This study reports on the clinical experiences at two institutions with mycophenolate mofetil ( MMF ) for severe lupus nephritis . Twelve patients with relapsing or resistant nephritis previously treated with cyclophosphamide therapy and one patient who refused cyclophosphamide as initial therapy for diffuse proliferative nephritis but accepted MMF were included . During combined MMF/prednisone therapy , serum creatinine values remained normal or declined from elevated values : mean change in serum creatinine was -0.26+/-0.46 microM/L , P = 0.039 . Proteinuria significantly decreased : mean change in urine protein-to-creatinine ratios was -2.53+/-3.76 , P = 0.039 . Decreased serum complement component C3 and elevated anti-double-str and ed DNA antibody levels at baseline improved in some , but not all , patients . The mean initial dose of MMF was 0.92 g/d ( range , 0.5 to 2 g/d ) . The mean duration of therapy was 12.9 mo ( range , 3 to 24 mo ) . Adverse events included herpes simplex stomatitis associated with severe leukopenia ( n = 1 ) , asymptomatic leukopenia ( n = 2 ) , nausea/ diarrhea ( n = 2 ) , thinning of scalp hair ( n = 1 ) , pancreatitis ( n = 1 ) , and pneumonia without leukopenia ( n = 1 ) . Recurrence of the pancreatitis led to discontinuation of MMF in this patient ; all other adverse events resolved with dose reduction . It is concluded that MMF is well tolerated and has possible efficacy in controlling major renal manifestations of systemic lupus erythematosus . Controlled clinical trials are needed to define the role of MMF in the management of lupus nephritis Pulse cyclophosphamide is more effective than prednisone alone in preventing renal failure in lupus nephritis . We undertook a r and omised , controlled trial to find out whether pulse methylprednisolone could equal pulse cyclophosphamide in preserving renal function in patients with lupus nephritis , and whether there was a difference between long and short courses of pulse cyclophosphamide in preventing exacerbations . 65 patients ( 60 female , 5 male ; median [ range ] age 29 [ 10 - 48 ] years ) with severe lupus nephritis were assigned r and omly to monthly pulse methylprednisolone for 6 months ( 25 patients ) , monthly pulse cyclophosphamide for 6 months ( 20 ) , or monthly cyclophosphamide for 6 months followed by quarterly pulse cyclophosphamide for 2 additional years ( 20 ) . Patients treated with pulse methylprednisolone had a higher probability of doubling serum creatinine than those treated with long-course cyclophosphamide ( p less than 0.04 ) . Risk of doubling creatinine was not significantly different between short and long course cyclophosphamide . However , patients treated with short-course cyclophosphamide had a higher probability of exacerbations than those treated with long-course cyclophosphamide ( p less than 0.01 ) . An extended course of pulse cyclophosphamide is more effective than 6 months of pulse methylprednisolone in preserving renal function in patients with severe lupus nephritis . Addition of a quarterly maintenance regimen to monthly pulse cyclophosphamide reduces the rate of exacerbations BACKGROUND The aim of the present study was to evaluate the efficacy of mycophenolate mofetil in the induction therapy of proliferative lupus nephritis . METHODS Forty-four patients from eight centres with newly diagnosed lupus nephritis World Health Organization class III or IV were r and omly assigned to either mycophenolate mofetil ( MMF ) 2 g/day for 6 months or intravenous cyclophosphamide ( IVC ) 0.75 - 1 g/m(2 ) monthly for 6 months in addition to corticosteroids . RESULTS Remission occurred in 13 out of 25 patients ( 52 % ) in the IVC group and 11 out of 19 patients ( 58 % ) in the MMF group ( P = 0.70 ) . There were 12 % in the IVC group and 26 % in the MMF group that achieved complete remission ( P = 0.22 ) . Improvements in haemoglobin , the erythrocyte sedimentation rate , serum albumin , serum complement , proteinuria , urinary activity , renal function and the Systemic Lupus Erythematosus Disease Activity Index score were similar in both groups . Twenty-four follow-up renal biopsies at the end of therapy showed a significant reduction in the activity score in both groups . The chronicity index increased in both groups but was only significant in the IVC group . Adverse events were similar . Major infections occurred in three patients in each group . There was no difference in gastrointestinal side-effects . CONCLUSIONS MMF in combination with corticosteroids is an effective induction therapy for moderately severe proliferative lupus nephritis Mycophenolate mofetil ( MMF ) and the sequential use of cyclophosphamide followed by azathioprine ( CTX-AZA ) demonstrate similar short-term efficacy in the treatment of diffuse proliferative lupus nephritis ( DPLN ) , but MMF is associated with less drug toxicity . Results from an extended long-term study , with median follow-up of 63 mo , that investigated the role of MMF as continuous induction-maintenance treatment for DPLN are presented . Thirty-three patients were r and omized to receive MMF , and 31 were r and omized to the CTX-AZA treatment arm , both in combination with prednisolone . More than 90 % in each group responded favorably ( complete or partial remission ) to induction treatment . Serum creatinine in both groups remained stable and comparable over time . Creatinine clearance increased significantly in the MMF group , but the between-group difference was insignificant . Improvements in serology and proteinuria were comparable between the two groups . A total of 6.3 % in the MMF group and 10.0 % of CTX-AZA-treated patients showed doubling of baseline creatinine during follow-up ( P = 0.667 ) . Both the relapse-free survival and the hazard ratio for relapse were similar between MMF- and CTX-AZA-treated patients ( 11 and nine patients relapsed , respectively ) and between those with MMF treatment for 12 or > /=24 mo . MMF treatment was associated with fewer infections and infections that required hospitalization ( P = 0.013 and 0.014 , respectively ) . Four patients in the CTX-AZA group but none in the MMF group reached the composite end point of end-stage renal failure or death ( P = 0.062 by survival analysis ) . It is concluded that MMF and prednisolone constitute an effective continuous induction-maintenance treatment for DPLN in Chinese patients The Phase III Aspreva Lupus Management Study ( ALMS ) will investigate mycophenolate mofetil ( MMF ) therapy for lupus nephritis ( LN ) . Eligibility criteria include : 12—75 years of age ; diagnosis of systemic lupus erythematosus according to revised American College of Rheumatology criteria ; and biopsy-demonstrated LN ( Class III — V ) . R and omized patients will receive open-label induction therapy with MMF or cyclophosphamide in combination with corticosteroids for 24 weeks . The primary efficacy endpoint is treatment response [ decreased proteinuria and stabilized ( within 25 % of baseline ) or improved serum creatinine level ] . Patients achieving response or complete remission ( normalization of all parameters ) will be rer and omized to double-blind , placebo-controlled maintenance treatment with MMF or azathioprine , both plus corticosteroids . The maintenance phase primary endpoint is time to treatment failure . To detect a 15 % rate improvement in the MMF group compared with cyclophosphamide , and to provide 90 % power , a total of 358 patients will be required for the induction phase . On the basis of a projected 278 rer and omized patients , the maintenance phase will have 90 % power to detect a difference between treatment groups assuming azathioprine and MMF three-year failure rates of 59.5 % and 40.7 % , respectively . Aspreva Lupus Management Study may provide invaluable comparative data on the efficacy and safety of MMF as LN induction and maintenance therapy . Lupus ( 2007 ) 16 , 972—980 OBJECTIVE To make an open label prospect i ve trial for comparing the therapeutic effects of mycophenolate mofetil ( MMF ) vs cyclophosphamide ( CYC ) pulse therapy on patients with diffuse proliferative lupus nephritis ( DPLN ) . METHODS Forty-six patients with biopsy proven active DPLN were enrolled in this study . Twenty-three patients were given MMF orally at a dosage of 1.0 - 1.5 g/d ( MMF Group ) . Another 23 cases received conventional intermittent CYC pulse therapy ( CYC Group ) . Supplemental steroid treatment was offered in the same manner to both groups . The age , sex distribution and severity of renal damage were matched in two groups . Therapeutic effects were evaluated at the end of six-month treatment . Fifteen patients in the MMF Group and 12 patients in the CYC Group had repeated renal biopsy at that time . RESULTS MMF therapy was more effective in reducing proteinuria and hematuria . A 50 % reduction of urinary protein and urinary red blood cell excretion from baseline value in 69.6 % and 91.3 % patients in the MMF Group , while only 47.8 % and 65.2 % in the CYC Group . MMF was more effective in inhibiting autoantibody production ( especially anti-dsDNA antibody ) and in decreasing serum cryoglobulin levels . Pathologically , the MMF group showed more markedly reduction in glomerular immune deposits with less glomerular necrosis , and less microthrombi , less crescent formation and vascular changes in the repeated renal biopsy as compared with the CYC group . Adverse reactions related to the treatment included gastrointestinal symptoms 26.1 % and 43.5 % in the MMF and CYC Groups respectively , infection 17.4 % in the MMF group and 30.4 % in the CYC group . CONCLUSION MMF was more effective in controlling the clinical activity of DPLN and renal vascular lesions as compared with CYC pulse therapy in a 6 month follow-up study Table . Drugs and Abbreviation Ovarian toxicity is an important consideration before the use of cyclophosphamide therapy in premenopausal women [ 1 ] . The deleterious effects of cyclophosphamide on ovarian function were noted in patients with rheumatoid arthritis treated with daily oral cyclophosphamide [ 2 ] . These preliminary observations have been confirmed and extended by subsequent studies in patients with various immune-mediated diseases including rheumatoid arthritis [ 3 ] , systemic lupus erythematosus [ 4 - 6 ] , ren Output:	Treatment of lupus nephritis with mycophenolate mofetil compared with cyclophosphamide reduces the risk for failure to induce remission during induction therapy and may reduce the risk for death or end-stage renal disease . Mycophenolate mofetil may be considered as a first-line induction therapy for the treatment of lupus nephritis in patients without severe renal dysfunction
MS212038	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Typical advice on the design and analysis of cluster r and omized trials ( C- RCTs ) focuses on allowance for the clustering at the level of the unit of allocation . However often C- RCTs are also organised spatially as may occur in the fields of Public Health and Primary Care where population s may even overlap . Methods We allowed for spatial effects on the error variance by a multiple membership model . These are a form of hierarchical model in which each lower level unit is a member of more than one higher level unit . Membership may be determined through adjacency or through Euclidean distance of centroids or in other ways such as the proportion of overlapping population . Such models may be estimated for Normal , binary and Poisson responses in Stata ( v10 or above ) as well as in WinBUGS or MLWin . We used this to analyse a dummy trial and two real , previously published cluster-allocated studies ( one allocating general practice s within one City and the other allocating general practice s within one County ) to investigate the extent to which ignoring spatial effects affected the estimate of treatment effect , using different methods for defining membership with Akaike 's Information Criterion to determine the " best " model . Results The best fitting model included both a fixed North-South gradient and a r and om cluster effect for the dummy RCT . For one of the real RCTs the best fitting model included both a r and om practice effect plus a multiple membership spatial term , while for the other RCT the best fitting model ignored the clustering but included a fixed North-South gradient . Alternative models which fitted only slightly less well all included spatial effects in one form or another , with some variation in parameter estimates ( greater when less well fitting models were included ) . Conclusions These particular results are only illustrative . However , we believe when design ing C- RCTs in a primary care setting the possibility of spatial effects should be considered in relation to the intervention and response , as well as any explanatory effect of fixed covariates , together with any implication s for sample size and methods for planned analyses Spatial analyses of the effect of insecticide (permethrin)-treated bed nets ( ITNs ) on nearby households both with and without ITNs was performed in the context of a large-scale , group-r and omized , controlled mortality trial in Asembo , western Kenya . Results illustrate a protective effect of ITNs on compounds lacking ITNs located within 300 meters of compounds with ITNs for child mortality , moderate anemia , high-density parasitemia , and hemoglobin levels . This community effect on nearby compounds without nets is approximately as strong as the effect observed within villages with ITNs . This implies that in areas with intense malaria transmission with high ITN coverage , the primary effect of insecticide-treated nets is via area-wide effects on the mosquito population and not , as commonly supposed , by simple imposition of a physical barrier protecting individuals from biting . The strength of the community effect depended upon the proportion of nearby compounds with treated nets . To maximize their public health impact , high coverage with treated nets is essential Research is needed to help identify interventions that will improve the capacity or functioning of health systems and thereby contribute to achieving global health goals . Well conducted , r and omized controlled trials ( RCTs ) , insofar as they reduce bias and confounding , provide the strongest evidence for identifying which interventions delivered directly to individuals are safe and effective . When ethically feasible , they can also help reduce bias and confounding when assessing interventions targeting entire health systems . However , additional challenges emerge when research focuses on interventions that target the multiple units of organization found within health systems . Hence , one can not complacently assume that r and omization can reduce or eliminate bias and confounding to the same degree in every instance . While others have articulated arguments in favour of alternative design s , this paper is intended to help people underst and why the potential value afforded by RCTs may be threatened . Specifically , it suggests six points to be borne in mind when exploring the challenges entailed in design ing or evaluating RCTs on health system interventions : ( i ) the number of units available for r and omization ; ( ii ) the complexity of the organizational unit under study ; ( iii ) the complexity of the intervention ; ( iv ) the complexity of the cause-effect pathway , ( v ) contamination ; and ( vi ) outcome heterogeneity . The authors suggest that the latter may be informative and that the reasons behind it should be explored and not ignored . Based on improved underst and ing of the value and possible limitations of RCTs on health system interventions , the authors show why we need broader platforms of research to complement RCTs Abstract Objectives To measure the impact on the dengue vector population ( Aedes aegypti ) and disease transmission of window curtains and water container covers treated with insecticide . Design Cluster r and omised controlled trial based on entomological surveys and , for Trujillo only , serological survey . In addition , each site had a non-r and omised external control . Setting 18 urban sectors in Veracruz ( Mexico ) and 18 in Trujillo ( Venezuela ) . Participants 4743 inhabitants ( 1095 houses ) in Veracruz and 5306 inhabitants ( 1122 houses ) in Trujillo . Intervention Sectors were paired according to entomological indices , and one sector in each pair was r and omly allocated to receive treatment . In Veracruz , the intervention comprised curtains treated with lambdacyhalothrin and water treatment with pyriproxyfen chips ( an insect growth regulator ) . In Trujillo , the intervention comprised curtains treated with longlasting deltamethrin ( PermaNet ) plus water jar covers of the same material . Follow-up surveys were conducted at intervals , with the final survey after 12 months in Veracruz and nine months in Trujillo . Main outcome measures Reduction in entomological indices , specifically the Breteau and house indices . Results In both study sites , indices at the end of the trial were significantly lower than those at baseline , though with no significant differences between control and intervention arms . The mean Breteau index dropped from 60 % ( intervention clusters ) and 113 % ( control ) to 7 % ( intervention ) and 12 % ( control ) in Veracruz and from 38 % to 11 % ( intervention ) and from 34 % to 17 % ( control ) in Trujillo . The pupae per person and container indices showed similar patterns . In contrast , in nearby communities not in the trial the entomological indices followed the rainfall pattern . The intervention reduced mosquito population s in neighbouring control clusters ( spill-over effect ) ; and houses closer to treated houses were less likely to have infestations than those further away . This created a community effect whereby mosquito numbers were reduced throughout the study site . The observed effects were probably associated with the use of material s treated with insecticide at both sites because in Veracruz , people did not accept and use the pyriproxyfen chips . Conclusion Window curtains and domestic water container covers treated with insecticide can reduce densities of dengue vectors to low levels and potentially affect dengue transmission SUMMARY An individual 's risk of infection from an infectious agent can depend on both the individual 's own risk and protective factors and those of individuals in the same community . We hypothesize that an individual 's exposure to an infectious agent is associated with the risks of infection of those living nearby , whether their risks are modified by pharmaceutical interventions or by other factors , because of the potential for transmission from them . For example , unvaccinated individuals living in a highly vaccinated community can benefit from indirect protection , or living near more children in a typhoid-endemic region ( where children are at highest risk ) might result in more exposure to typhoid . We tested this hypothesis using data from a cluster-r and omized typhoid vaccine trial . We first estimated each individual 's relative risk of confirmed typhoid outcome using their vaccination status and age . We defined a new covariate , potential exposure , to be the sum of the relative risks of all who live within 100 m of each person . We found that potential exposure was significantly associated with an individual 's typhoid outcome , and adjusting for potential exposure affected estimates of vaccine efficacy . We suggest that it is useful and feasible to adjust for spatially heterogeneous distributions of individual-level risk factors , but further work is required to develop and test such approaches OBJECTIVES Insecticide-treated bednets ( ITNs ) are effective in preventing nocturnally transmitted vector-borne diseases , but their effect on diurnally active dengue vectors has never been studied . We investigated the efficacy of ITNs in reducing Aedes aegypti population s and dengue transmission . METHODS A cluster-r and omized trial was carried out in Leogane , Haiti between July 2003 and July 2004 . The study area ( 1017 houses ) was divided into 18 sectors ( clusters ) : nine received ITNs ( Olyset(R ) long-lasting insecticidal bednets ) and nine were untreated controls . Entomological surveys [ measuring Breteau ( BI ) , house ( HI ) , container ( CI ) and pupae per person ( PPI ) indices and oviposition activity ] were undertaken at baseline and at 1 and 5 months post-intervention . All houses were georeferenced to enable spatial analysis . Control sectors received ITNs at 6 months , and a final entomological and attitudinal survey was undertaken at 12 months after baseline . Anti-dengue IgM seropositivity rates were measured at baseline and after 12 months . Efficacy of ITNs was assessed by WHO cone bioassays . RESULTS At 1-month post-intervention , entomological indices fell in all sectors , with HI and BI in the bednet sectors reduced by 6.7 ( 95 % CI -10.6 , -2.7 ; P < 0.01 ) and 8.4 ( 95 % CI -14.1 , -2.6 ; P < 0.01 ) respectively . Moreover at 1 month , ovitraps in control sectors were significantly more likely to be positive than in bednet sectors ( P < 0.01 ) . By 5 months , all indices remained low and HI , CI and BI were also significantly lower than that of baseline in the control arm . Curiously , at 5 months , HI , CI and BI were lower in the control arm than that in the bednet arm . A final survey , 12 months after the initial baseline study ( 5 months after bednets had been given to all households ) indicated that all indices were significantly lower than that at baseline ( P < 0.001 ) . Control houses located within 50 m of a bednet house had significantly lower CI ( Z = -2.67 , P = 0.008 ) and PPI ( Z = -2.19 , P = 0.028 ) at 1 month , an effect that extended to 100 m by 5 months ( Z = -2.03 , P = 0.042 and Z = -2.37 , P = 0.018 respectively ) , suggesting a spill-over effect of the bednets . An IgM serosurvey showed a 15.3 % decrease ( 95 % CI 5.0 - 25.5 % , P < 0.01 ) in the number of IgM-positive individuals from baseline to12 months later . CONCLUSIONS Insecticide-treated bednets had an immediate effect on dengue vector population s after their introduction , and over the next 5 - 12 months , the presence of ITNs may have continued to affect vector population s and dengue transmission This paper identifies spatial patterns and predictors of vaccine uptake in a cluster-r and omized controlled trial in Hue , Vietnam . Data for this study result from the integration of demographic surveillance , vaccine record , and geographic data of the study area . A multi-level cross-classified ( non-hierarchical ) model was used for analyzing the non-nested nature of individual 's ecological data . Vaccine uptake was unevenly distributed in space and there was spatial variability among predictors of vaccine uptake . Vaccine uptake was higher among students with younger , male , or not literate family heads . Students from households with higher per-capita income were less likely to participate in the trial . Residency south of the river or further from a hospital/polyclinic was associated with higher vaccine uptake . Younger students were more likely to be vaccinated than older students in high- or low-risk areas , but not in the entire study area . The findings are important for the management of vaccine campaigns during a trial and for interpretation of disease patterns during vaccine-efficacy evaluation Effects of the distribution in space of permethrin (insecticide)-impregnated bed nets ( IIBNS ) on child mortality were studied in a r and omized controlled trial of IIBNs in a an area highly endemic for Plasmodium falciparum malaria in rural northern Ghana . Eight hundred sixty-two deaths occurred among children 6 - 59 months of age during 16,841 child-years-at-risk . Mortality increased with the distance from health facilities but not with proximity to identifiable anopheline breeding sites ( reservoirs ) . The efficacy of IIBNs was independent of these distances . Mortality in users of IIBNs was independent of the proximity of nonusers , and mortality rates of nonusers and users living close to each other were similar . Poisson regression estimated a 6.7 % increase in mortality among nonusers with each 100-m shift away from the nearest compound with IIBNS , indicating that the insecticide protects nearby nonusers . High coverage of IIBNs achieves maximum impact , but users of IIBNs offer some protection to less fortunate neighbors if coverage is incomplete The effect of insecticide (permethrin)-treated bed nets ( ITNs ) on the spatial distribution of malaria vectors in neighboring villages lacking ITNs was studied during a r and omized controlled trial of ITNs in western Kenya . There was a trend of decreased abundance of Anopheles gambiae with decreasing distance from intervention villages both before ( P = 0.027 ) and after ( P = 0.002 ) introduction of ITNs , but this trend was significantly stronger after ITNs were introduced ( P = 0.05 ) . For An . funestus , no pre-intervention trend was observed ( P = 0.373 ) Output:	The spatial variable approach was most common and involved st and ard statistical analysis of distance measurements . Studies tended to demonstrate the importance of accounting for location and distribution of observations in estimating unbiased effects .
MS212039	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective : The presence of co-morbid depressive symptoms may have a negative impact on the management of diabetes mellitus . Moreover , some antidepressants may adversely affect glycemic control . Selective serotonin reuptake inhibitors ( SSRIs ) may improve glycemic control and may be beneficial for patients with co-morbid depression and diabetes . We examined the safety and efficacy of s-citalopram therapy in patients with co-morbid depression and diabetes , and its ability to improve glycemic control . Research Design and Methods : 17 patients were enrolled into the trial and 14 patients received open-label s-citalopram therapy for up to 16 weeks . Clinical outcome measures included the 17-item Hamilton depression rating ( HAM-D 17 ) and the clinical global impressions severity ( CGI/S ) and change ( CGI/C ) ratings . In addition , fasting glucose , fructosamine , and glycosylated hemoglobin-A1C measures were obtained before and during s-citalopram therapy . Results : We observed a significant reduction in mean HAM-D 17 ( p < 0.001 ) , CGI/S ( p = 0.001 ) and CGI/C ( p = 0.001 ) ratings during s-citalopram therapy . We also observed a modest , non-significant reduction in fasting glucose , fructosamine , and glycosylated hemoglobin-A1C levels during s-citalopram therapy . Limitation : Limitations of this study include a modest patient sample size and a 16-week treatment duration which may have been insufficient to demonstrate the full effect of SSRI therapy on glycemic control . Conclusion : We observed a significant reduction in depressive symptoms and modest , non-significant reductions in fasting glucose , fructosamine , and glycosylated hemoglobin-A1C levels during SSRI therapy of co-morbid depression and diabetes To evaluate the efficacy and safety of oral magnesium supplementation , with magnesium chloride ( MgCl2 ) , in the treatment of newly diagnosed depression in the elderly with type 2 diabetes and hypomagnesemia . Twenty-three elderly patients with type 2 diabetes and hypomagnesemia were enrolled and r and omly allocated to receive either 50 mL of MgCl2 5 % solution equivalent to 450 mg of elemental magnesium or Imipramine 50 mg daily during 12 weeks . Widowhood or divorce in the last six months , alcoholism , degenerative illnesses of the nervous central system , recent diagnosis of diabetes , previous or current treatment with antidepressants , chronic diarrhea , use of diuretics , and reduced renal function were exclusion criteria . Hypomagnesemia was defined by serum magnesium levels < 1.8 mg/dL and depression by Yasavage and Brink score > or = 11 points . The primary trial end point was the improvement of depression symptoms . At baseline , there were no differences by age ( 69 + /- 5.9 and 66.4 + /- 6.1 years , p = 0.39 ) , duration of diabetes ( 11.8 + /- 7.9 and 8.6 + /- 5.7 years , p = 0.33 ) , serum magnesium levels ( 1.3 + /- 0.04 and 1.4 + /- 0.04 mg/dL , p = 0.09 ) , and Yasavage and Brink Score ( 17.9 + /- 3.9 and 16.1 + /- 4.5 point , p = 0.34 ) in the groups with MgCl2 and imipramine , respectively . At end of follow-up , there were no significant differences in the Yasavage and Brink score ( 11.4 + /- 3.8 and 10.9 + /- 4.3 , p = 0.27 ) between the groups in study ; whereas serum magnesium levels were significantly higher in the group with MgCl2 ( 2.1 + /- 0.08 mg/dL ) than in the subjects with imipramine ( 1.5 + /- 0.07 mg/dL ) , p < 0.0005 . In conclusion , MgCl2 is as effective in the treatment of depressed elderly type 2 diabetics with hypomagnesemia as imipramine 50 mg daily CONTEXT In patients with diabetes mellitus , depression is a prevalent and recurrent problem that adversely affects the medical prognosis . OBJECTIVE To determine whether maintenance therapy with sertraline hydrochloride prevents recurrence of major depression in patients with diabetes . DESIGN A r and omized , double-blind , placebo-controlled , maintenance treatment trial . Patients who recovered from depression during open-label sertraline treatment continued to receive sertraline ( n = 79 ) or placebo ( n = 73 ) and were followed up for up to 52 weeks or until depression recurred . SETTING Outpatient clinics at Washington University , St Louis , MO , the University of Washington , Seattle , and the University of Arizona , Tucson . PATIENTS One hundred fifty-two patients with diabetes ( mean age , 52.8 years ; 59.9 % female ; 82.9 % with type 2 diabetes ) who recovered from major depression ( 43.3 % of those initially assigned ) during 16 weeks of open-label treatment with sertraline ( mean dose , 117.9 mg/d ) . INTERVENTION Sertraline continued at recovery dose or identical-appearing placebo . MAIN OUTCOME MEASURES The primary outcome was length of time ( measured as the number of days after r and omization ) to recurrence of major depression as defined in DSM-IV . The secondary outcome was glycemic control , which was assessed via serial determinations of glycosylated hemoglobin levels . RESULTS Sertraline conferred significantly greater prophylaxis against depression recurrence than did placebo ( hazard ratio = 0.51 ; 95 % confidence interval , 0.31 - 0.85 ; P = .02 ) . Elapsed time before major depression recurred in one third of the patients increased from 57 days in patients who received placebo to 226 days in patients treated with sertraline . Glycosylated hemoglobin levels decreased during the open treatment phase ( mean + /- SD glycosylated hemoglobin level reduction , -0.4 % + /- 1.4 % ; P = .002 ) . Glycosylated hemoglobin levels remained significantly lower than baseline during depression-free maintenance ( P = .002 ) and did not differ between treatment groups ( P = .90 ) . CONCLUSIONS In patients with diabetes , maintenance therapy with sertraline prolongs the depression-free interval following recovery from major depression . Depression recovery with sertraline as well as sustained remission with or without treatment are associated with improvements in glycosylated hemoglobin levels for at least 1 year BACKGROUND This study aims to investigate the efficacy of fluoxetine and paroxetine on the levels of depression-anxiety , quality of life , disability , and metabolic control in type II diabetes mellitus ( DM ) patients . METHODS The patients were first applied the Hospital Anxiety-Depression Scale ( HADS ) . After a psychiatric interview with patients who had scores above the cut-off point , those who were diagnosed as having a major depressive disorder according to DSM-IV criteria were applied the Hamilton Depression Rating Scale ( HDRS ) and the Hamilton Anxiety Rating Scale ( HARS ) . Twenty three patients who scored 16 or above on the HDRS were included in the study and given the Short Form-36 ( SF-36 ) , and the Brief Disability Question naire ( BDQ ) and HbA1c levels were measured . Patients were r and omized on 20 mg/day fluoxetine or 20 mg/day paroxetine treatment . The patients were evaluated with the same scales at the 2(nd ) , 4(th ) , 6(th ) , and the 12(th ) weeks . RESULTS Both groups showed a statistically significant decrease in HDRS , HARS , and BDQ scores with comparison to the index assessment . At the end of treatment , though not statistically significant , a decrease was observed in HbA1c values of the fluoxetine-administered group . CONCLUSIONS Fluoxetine and paroxetine effectively reduce the severity of major depressive disorder in type II DM patients . There is need for further and longer-lasting monitoring studies with more patients in order to determine whether there is any difference in terms of their effects on glycemic control OBJECTIVE To determine whether pharmacological treatment of depression in low-income minorities with diabetes improves A1C and quality of life ( QOL ) . RESEARCH DESIGN AND METHODS This was a 6-month , r and omized , double-blind , placebo-controlled trial . Patients were screened for depression using Whooley 's two- question tool at a county diabetes clinic . Depression was confirmed ( or not ) with the Computerized Diagnostic Interview Survey ( CDIS ) software program , and the severity of depression was assessed monthly by the Hamilton Depression Scale ( HAM-D ) . Depressed subjects with A1C levels ≥8.0 % were r and omly assigned to receive either sertraline or placebo . Diabetes care was provided by nurses following detailed treatment algorithms who were unaware of therapy for depression . RESULTS A total of 150 subjects answered positively to at least one question on Whooley 's question naire . The positive predictive value for depression diagnosed by CDIS was 69 , 67 , and 84 % for positive answers to question 1 only , question 2 only , or both , respectively . Of the 89 subjects who entered the study , 75 completed . An intention-to-treat analysis revealed significant differences between baseline and 6 months in HAM-D and pain scores , QOL , and A1C and systolic blood pressure levels in both groups , with no differences between groups for the first three but a significantly greater decrease with sertraline in A1C and systolic blood pressure levels . Changes in HAM-D scores and A1C levels were significantly correlated in all subjects ( P = 0.45 [ P < 10−6 ] ) . CONCLUSIONS In this low-income minority population , pharmacological treatment of depression significantly improved A1C and systolic blood pressure levels compared with placebo OBJECTIVE Depression is prevalent in patients with diabetes . It is associated with poor glycemic control and is linked to an increased risk for diabetic complications . In this study , we assessed the efficacy of fluoxetine for depression in patients with diabetes . RESEARCH DESIGN AND METHODS Sixty patients with diabetes ( type 1 , n = 26 ; type 2 , n = 34 ) and major depressive disorder entered an 8-week r and omized placebo-controlled double-blind trial . Patients were given daily doses of fluoxetine ( up to 40 mg/day ) . The Beck Depression Inventory ( BDI ) and Hamilton Rating Scale for Depression ( HAMD ) were used to measure the severity of depression and to determine the percentage of patients who achieved substantial improvement or complete remission . GHb levels were obtained to monitor glycemic control . RESULTS Reduction in depression symptoms was significantly greater in patients treated with fluoxetine compared with those receiving placebo ( BDI , -14.0 vs. -8.8 , P = 0.03 ; HAMD , -10.7 vs. -5.2 , P = 0.01 ) . The percentage of patients achieving a significant improvement in depression per the BDI was also higher in the fluoxetine group ( 66.7 vs. 37.0 % , P = 0.03 ) . Additionally , trends toward a greater rate of depression remission ( 48.1 vs. 25.9 % , P = 0.09 per the HAMD ) and greater reduction in GHb ( -0.40 vs. -0.07 % , P = 0.13 ) were observed in the fluoxetine group . CONCLUSIONS Fluoxetine effectively reduces the severity of depression in diabetic patients . Our study demonstrated that after only 8 weeks , this treatment also produced a trend toward better glycemic control OBJECTIVES Depression is prevalent in patients with type 2 diabetes and affects quality of life . The prevalence of depression in the sample of Croatian patients with diabetes is 32.2 % . The main aim of the investigation was to evaluate the effect of antidepressant treatment on quality of life and metabolic control in depressed diabetic patients . DESIGN AND METHODS In the sample we r and omized 60 diabetic out patients with optimally controlled diabetes and with depression . The efficacy of 50 mg sertraline per day treatment was tested by the MADRAS question naire in a 24-week period , where the patients controlled themselves . Changes in the quality of life as the consequences of treatment of depression were tested by the QLSQ question naire for the quality of life follow-up . RESULTS The MADRAS scale results , measuring the changes in the degree of depression , showed substantial improvement of condition throughout the whole treatment . The first eight weeks of treatment presented statistically high significance in examinees in all the groups of chronic somatic diseases . The QLSQ scale results for measuring the quality of life showed marked improvement . Statistically significant changes occurred during the first eight weeks of treatment . Two patients withdrew their consent before starting medication and 13 dropped out later in the study . Treatment of depression with sertraline in chronic som Output:	In total , we ended up with 18 articles for our purpose s. RESULTS The combination of depression and DM may be harmful as depression has a strong impact on psychosocial and medical outcomes in patients with DM . It showed that depression improvement had a favourable effect on glycaemic control that was weight independent . Bear in mind that there is a possible risk of hypoglycemia when using SSRIs .
MS212040	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Little is known about the effects of successful psychotherapy on brain function in subjects with anxiety disorders . The present study aim ed to identify changes in brain activation following cognitive-behavioral therapy ( CBT ) in subjects suffering from specific phobia . Using functional magnetic resonance imaging ( fMRI ) , brain activation to spider videos was measured in 28 spider phobic and 14 healthy control subjects . Phobics were r and omly assigned to a therapy-group ( TG ) and a waiting-list control group ( WG ) . Both groups of phobics were scanned twice . Between scanning sessions , CBT was given to the TG . Before therapy , brain activation did not differ between both groups of phobics . As compared to control subjects , phobics showed greater responses to spider vs. control videos in the insula and anterior cingulate cortex ( ACC ) . CBT strongly reduced phobic symptoms in the TG while the WG remained behaviorally unchanged . In the second scanning session , a significant reduction of hyperactivity in the insula and ACC was found in the TG compared to the WG . These results propose that increased activation in the insula and ACC is associated with specific phobia , whereas an attenuation of these brain responses correlates with successful therapeutic intervention BACKGROUND Animal studies demonstrate that stress and negative affect enhance the release of the neuropeptide substance P ( SP ) , which binds to the neurokinin 1 ( NK1 ) receptor . This positron emission tomography ( PET ) study evaluated how the activity in the SP-NK1 receptor system in the amygdala was affected by fear provocation in subjects with specific phobia . METHODS Sixteen adult women with DSM-IV-defined specific phobia for either snakes or spiders but not both viewed pictures of feared and non-feared animals while being PET-scanned for 60 min with the highly specific NK1 receptor antagonist [(11)C]GR205171 as the labeled PET tracer . RESULTS The uptake of the labeled NK1 receptor antagonist was significantly reduced in the right amygdala during phobic stimulation . In the left amygdala no significant differences were found between phobic and non-phobic conditions . There was a negative correlation in the right , but not left , amygdala between subjective anxiety ratings and NK1 tracer binding . CONCLUSIONS Fear provocation affects the SP-NK1 receptor system in the right amygdala . This reflects reduced NK1 receptor availability during fear and could mirror an increased release of endogenous substance Neurofunctional mechanisms underlying cognitive behavior therapy ( CBT ) are still not clearly understood . This functional magnetic resonance imaging ( fMRI ) study focused on changes in brain activation as a result of one-session CBT in patients suffering from spider phobia . Twenty-six female spider phobics and 25 non-phobic subjects were presented with spider pictures , generally disgust-inducing , generally fear-inducing and affectively neutral scenes in an initial fMRI session . Afterwards , the patients were r and omly assigned to either a therapy group ( TG ) or a waiting list group ( WG ) . The scans were repeated one week after the treatment or after a one-week waiting period . Relative to the non-phobic participants , the patients displayed increased activation in the amygdala and the fusiform gyrus as well as decreased activation in the medial orbitofrontal cortex ( OFC ) during the first exposure . The therapy effect consisted of increased medial OFC activity in the TG relative to the WG . Further , therapy-related reductions in experienced somatic anxiety symptoms were positively correlated with activation decreases in the amygdala and the insula . We conclude that successful treatment of spider phobia is primarily accompanied by functional changes of the medial OFC . This brain region is crucial for the self-regulation of emotions and the relearning of stimulus-reinforcement associations Forty-six patients with spider phobia , fulfilling the DSM-IV criteria for specific phobia , were assessed with behavioral , physiological and self-report measures . They were r and omly assigned to three group treatment conditions : ( 1 ) direct treatment ; ( 2 ) direct observation ; and ( 3 ) indirect observation . All treatments were carried out in large groups of eight patients , and consisted of one 3 hr session of massed exposure and modelling . The results showed that on the behavioral test , measures and the specific self-report measures of spider phobia the direct treatment was significantly better than direct observation and indirect observation , which did not differ . On the physiological measures and the psychopathology self-report measures there were significant pre-post improvements , but no differences between the groups . The effects were maintained or furthered at the one year follow-up assessment . The proportion of clinical ly significantly improved patients were , at post-treatment , 75 % in the direct treatment , 7 % in the direct observation , and 31 % in the indirect observation group . At follow-up , the corresponding figures were 75 , 14 , and 44 % , respectively . The conclusion that can be drawn is that direct treatment is the treatment of choice BACKGROUND Exposure-based therapy for anxiety disorders is believed to operate on the basis of fear extinction . Studies have shown acute administration of D-cycloserine ( DCS ) enhances fear extinction in animals and facilitates exposure therapy in humans , but the neural mechanisms are not completely understood . To date , no study has examined neural effects of acute DCS in anxiety-disordered population s. METHODS Two hours prior to functional magnetic resonance imaging scanning , 23 spider-phobic and 23 non-phobic participants were r and omized to receive DCS 100 mg or placebo . During scanning , participants viewed spider , butterfly , and Gaussian-blurred baseline images in a block- design paradigm . Diagnostic and treatment groups were compared regarding differential activations to spider versus butterfly stimuli . RESULTS In the phobic group , DCS enhanced prefrontal ( PFC ) , dorsal anterior cingulate ( ACC ) , and insula activations . For controls , DCS enhanced ventral ACC and cau date activations . There was a positive correlation between lateral PFC and amygdala activation for the placebo-phobic group . Reported distress during symptom provocation was correlated with amygdala activation in the placebo-phobic group and orbitofrontal cortex activation in the DCS-phobic group . CONCLUSIONS Results suggest that during initial phobic symptom provocation DCS enhances activation in regions involved in cognitive control and interoceptive integration , including the PFC , ACC , and insular cortices for phobic participants BACKGROUND The study aim ed to identify brain activation during direct and automatic processing of phobogenic stimuli in specific phobia . METHODS Responses to phobia-related and neutral pictures ( spiders and mushrooms ) were measured by means of event-related functional magnetic resonance imaging during two different tasks . In the identification task , subjects were asked to identify the object ( spider or mushroom ) . In a dem and ing distraction task , subjects had to match geometric figures displayed in the foreground of the pictures . RESULTS Phobics showed greater responses to spiders versus mushrooms in the left amygdala , left insula , left anterior cingulate gyrus ( ACC ) , and left dorsomedial prefrontal cortex ( DMPFC ) during the identification task and in the left and right amygdala during the distraction task . All of these activations were also significantly increased compared to control subjects who did not show stronger brain activation to spiders versus mushrooms under any task condition . CONCLUSIONS Our findings propose specific neural correlates of automatic versus direct evaluation of phobia-relevant threat . While the amygdala , especially the right amygdala , seems to be crucially involved in automatic stimuli processing , activation of areas such as the insula , ACC and DMPFC is rather associated with direct threat evaluation and requires sufficient attentional re sources Previous imaging studies of obsessive-compulsive symptom states have implicated frontal-striatal and limbic regions in the pathophysiology of obsessive-compulsive disorder ( OCD ) . Functional imaging studies , however , have yielded inconsistent results , presumably due to method ological differences ( patient inclusion criteria , stimulus paradigm , imaging technique , and absence of control groups ) . In the present study , r and omized presentation of contamination-related and neutral visual stimuli was used to investigate the neurophysiological correlates of contamination fear in a group of medication-free OCD patients with washing behaviors and healthy controls . A total of 21 subjects ( 11 OCD patients and 10 healthy controls ) were scanned using H(2)(15)O positron emission tomography ( PET ) . Subjects were presented with pictures of clean and dirty surroundings and were requested to make indoor/outdoor decisions to control for attention differences . State anxiety and obsessionality were rated after each scan using visual analogue scales . Main effects of stimulus type ( contamination vs. neutral ) were found in bilateral occipital cortex in both groups . A significant group interaction effect was observed in the left amygdala reflecting enhanced activity in response to contamination stimuli in OCD patients . Sensitization effects were observed in the right amygdala in the OCD group ; these paralleled an increase in levels of distress and obsessionality as well as a decrease in dorsolateral prefrontal activity . The findings of the present study are consistent with the hypothesis of decreased frontal-striatal control of limbic structures , specifically the amygdala , result ing in an inadequate fear response in OCD patients with contamination fear This study evaluated the efficacy of behavioral and cognitive-behavioral one-session exposure treatment procedures with and without programmed generalization for participants with small animal phobias . Forty participants were r and omly assigned to the treatment and generalization conditions . Both treatments produced significant improvements from pre-test to post-test and these results were maintained for 1 year . The treatment effect sizes ranged from large to very large across behavioral , self-report , and subjectively rated measures . Participants in the behavioral treatment condition reported that the treatment was significantly more intrusive than participants in the cognitive-behavioral treatment group . The programmed generalization condition did not produce additional measured benefit . The results are discussed in terms of the overall effectiveness of one-session exposure treatment components for small animal phobias OBJECTIVE This study investigated the neural substrates of implicit sequence learning in subjects with and without small animal phobia , in a follow-up to analogous studies of obsessive-compulsive disorder ( OCD ) . METHOD Ten subjects with specific phobia and 10 healthy comparison subjects were studied by using a serial reaction time task paradigm and functional magnetic resonance imaging . RESULTS A main effect of condition ( implicit sequence learning versus r and om sequence ) was observed across diagnostic groups in the right striatum , as well as in other regions . In the striatum , the a priori region of interest , there were no significant effects of diagnosis or the interaction of diagnosis and condition . CONCLUSIONS Brain activation in the striatum of subjects with specific phobia does not significantly differ from that of normal comparison subjects during implicit sequence learning . This suggests different pathophysiological mechanisms for specific phobia in contrast to OCD , in which deficient striatal recruitment has been reproducibly found with this paradigm . This approach offers promise for demonstrating diagnostic specificity across different neuropsychiatric disorders based on the presence or absence of deficient striatal activation We investigated central nervous system correlates of simple phobic fear . Regional cerebral blood flow ( rCBF ) was measured using positron emission tomography ( PET ) in eight volunteers with symptomatic spider phobia that were exposed to visual phobogenic and neutral stimuli . Diazepam ( 0.1 mg/kg body weight i.v . ) or placebo was administered under double-blind conditions after initial PET scans . The PET scans were then repeated . The presence of fear was confirmed by rating procedures and increased number of nonspecific electrodermal fluctuations and by higher heart rate during phobic than during neutral stimulation . Phobic as compared to neutral stimulation elevated the regional to whole brain ( relative ) CBF in the secondary visual cortex but reduced relative rCBF in the hippocampus , prefrontal , orbitofrontal , temporopolar , and posterior cingulate cortex . Diazepam treatment did not affect the relative rCBF or the subjective or physiological fear indices . The observed rCBF pattern replicates our previous findings in snake phobics ( M. Fredrikson et al. [ 1993 ] Psychophysiology , 30 , 127 - 131 ; G. Wik et al. [ 1993 ] Psychiatry Research ( Neuroimaging ) , 50 , 15 - 24 ) and indicates that fear and anxiety affect cortical areas outside the classic limbic system areas Positron emission tomography was employed to contrast the brain activation pattern in patients with obsessive-compulsive disorder ( OCD ) to that of matched control subjects while they performed an implicit learning task . Although patients and control subjects evidence d comparable learning , imaging data from control subjects indicated bilateral inferior striatal activation , whereas OCD patients did not activate right or left inferior striatum and instead showed bilateral medial temporal activation . The findings further implicate corticostriatal dysfunction in obsessive-compulsive disorder . Furthermore , when OCD patients are confronted with stimuli that call for recruitment of corticostriatal systems , they instead appear to access brain regions normally associated with explicit ( conscious ) information processing Fifty-two patients with spider phobia , fulfilling the DSM-III-R criteria for simple phobia , were assessed with behavioral , physiological and self-report measures . They were r and omly assigned to five different treatment conditions : ( 1 ) one session therapist-directed exposure ( maximum 3 hours ) , ( 2 ) specific manual-based treatment in the home , ( 3 ) specific manual-based treatment at the clinic , ( 4 ) general manual-based treatment in the home and ( 5 ) general manual-based treatment at the clinic . The results show that therapist-directed one-session treatment was significantly more effective than three of the manual-based treatments , both at the post-treatment and follow-up stages . Specific manual-based treatment at the clin Output:	RESULT The search showed that studies in this area were published recently and that the neuroanatomic substrate of SP has not yet been consoli date d. CONCLUSION In spite of method ological differences among studies , results converge to a greater activation in the insula , anterior cingulate cortex , amygdala , and prefrontal and orbitofrontal cortex of patients exposed to phobia-related situations compared to controls . These findings support the hypotheses of the hyperactivation of a neuroanatomic structural network involved in SP
MS212041	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The aim of this study was to determine the association between drug type and arrest for driving under the influence of drugs ( DUID ) by calculating odds ratios ( ORs ) using a case-control design . A DUID arrest is in most cases related to aberrant or risky driving and might therefore be regarded as a proxy for a drug related traffic crash . The ' cases ' were 2738 drivers arrested on suspicion of drugged driving from April 2008 to March 2009 with blood alcohol concentrations below the legal limit of 0.2g/L ; 794 were arrested due to involvement in road traffic crashes , whereas 1944 were arrested for other reasons , mainly dangerous driving , suspected impairment when stopped in traffic controls , or because of phone calls to the police from other road users or observers . The ' controls ' were 9375 r and om drivers in normal traffic , also with alcohol concentrations below this limit . Blood sample s from ' cases ' and oral fluid sample s from ' controls ' were analyzed for 15 drugs that have legislative concentration limits in Norway , in addition to two other commonly detected psychoactive drugs . The most prevalent illicit drug in the control group was tetrahydrocannabinol ( THC ; 0.58 % ) , which was also commonly found in sample s from drivers arrested due to road crash ( 15.6 % ) or arrested for other reasons ( 21.8 % ) . Amphetamine/methamphetamine was most prevalent among arrested drivers involved in crashes ( 30.6 % ) and drivers arrested for other reasons ( 56.9 % ) , whereas only 0.18 % of the control group was positive for amphetamine/methamphetamine . The single-use substances which gave highest OR for police arrest were amphetamine/methamphetamine , alprazolam , clonazepam and oxazepam . The majority of the alprazolam and clonazepam findings were probably due to non-therapeutic use of medicinal drugs purchased on the illegal market . Combinations of two or more drugs yielded higher ORs than the use of single substances ; combinations of amphetamine/methamphetamine and benzodiazepines gave the highest risk Rationale In party circuits dexamphetamine is frequently used in combination with alcohol . It is hypothesized that co-administration of dexamphetamine to alcohol might reduce the sedative effects of alcohol , but may potentiate risk-taking behaviour . Objectives The study was aim ed at assessing the effects of alcohol , dexamphetamine and the combination of both on simulated driving and cognitive performance . Method Eighteen subjects participated in a r and omized , crossover , placebo-controlled study employing four conditions : 10 mg dexamphetamine , 0.8 g/kg alcohol , 10 mg dexamphetamine + 0.8 g/kg alcohol , and placebo . Fundamental driving skills and risk-taking behaviour were assessed in a driving simulator . Subjects also completed vigilance and divided attention tasks , and subjective ratings . Results Mean BAC levels during simulated driving were between 0.91‰ and 0.64‰. Subjects using alcohol showed a significantly larger mean st and ard deviation of lateral position and shorter accepted gap time and distance . Use of alcohol or dexamphetamine + alcohol was associated with a higher frequency of red light running and collisions than the dexamphetamine or placebo conditions . Performance of vigilance and divided attention tasks was significantly impaired in the alcohol condition and , to a lesser degree , in the dexamphetamine + alcohol condition . ConclusionS ingle doses of 0.8 g/kg alcohol increased risk-taking behaviours and impaired tracking , attention and reaction time during a 3-h period after drinking when BACs declined from 0.9 to 0.2 mg/ml . The stimulatory effects of co-administration of dexamphetamine 10 mg were not sufficient to overcome the impairing effects of alcohol on skills related to driving Using a cover story of the effects of alcohol on perceptual and motor abilities , two levels of alcohol consumed ( moderate and none ) , two levels of alcohol expectancy ( moderate and none ) , and two levels of sensation seeking ( high and low ) were combined to determine their effect on risk taking in a driving simulator . Ninety-six subjects were r and omly assigned to eight conditions . Dependent variables were lane changes-cars passed and time at maximum speed . Results on lane-changes-cars passed indicated greater risk-taking in driving by high sensation seekers . Interaction of alcohol expectancy and sensation seeking indicated high sensation seekers took more risks when they believed they had consumed alcohol . Low sensation seekers became more cautious in driving when they believed they had consumed alcohol . Alcohol consumed did not produce a significant main effect or interaction The present investigation employed a balanced placebo design to examine the effects of alcohol versus the belief that one has consumed alcohol , i.e. alcohol expectancy , on error production while operating a driving simulator . The male subjects employed were social drinkers , having no history of alcohol abuse . The alcoholic beverage consisted of vodka and tonic in the ratio of 1:5 , result ing in a mean blood alcohol level of .064 % . The placebo beverage consisted of water and tonic , also in the ration 1:5 . Principal findings were that alcohol ingestion had a debilitating effect on certain measures of driving behavior ( operation of brakes , steering ) , whereas the belief that one had consumed alcohol had no discernable effects . The results are discussed in relation to other findings using the balanced placebo design . It was concluded that reckless driving under the influence of alcohol , is at least partly a result of the pharmological effects of ethanol Rationale The driving simulator provides a safe and controlled environment for testing driving behaviour efficiently . The question is whether it is sensitive to detect drug-induced effects . Objective The primary aim of the current study was to investigate the sensitivity of the driving simulator for detecting drug effects . As a case in point , we investigated the dose-related effects of oral ∆9-tetrahydrocannabinol ( THC ) , i.e. dronabinol , on simulator and on-the-road driving performance in equally dem and ing driving tasks . Method Twenty-four experienced driver participants were treated with dronabinol ( Marinol ® ; 10 and 20 mg ) and placebo . Dose-related effects of the drug on the ability to keep a vehicle in lane ( weaving ) and to follow the speed changes of a lead car ( car following ) were compared within subjects for on-the-road versus in-simulator driving . Additionally , the outcomes of equivalence testing to alcohol-induced effects were investigated . Results Treatment effects found on weaving when driving in the simulator were comparable to treatment effects found when driving on the road . The effect after 10 mg dronabinol was however less strong in the simulator than on the road and inter-individual variance seemed higher in the simulator . There was , however , a differential treatment effect of dronabinol on reactions to speed changes of a lead car ( car following ) when driving on the road versus when driving in the simulator . Conclusion The driving simulator was proven to be sensitive for demonstrating dronabinol-induced effects particularly at higher doses . Treatment effects of dronabinol on weaving were comparable with driving on the road but inter-individual variability seemed higher in the simulator than on the road which may have potential effects on the clinical inferences made from simulator driving . Car following on the road and in the simulator were , however , not comparable The Lane Change Task was developed to provide an objective safety criterion for the assessment of driver distraction by in-vehicle information systems ( IVIS ) . It consists of two basic driving tasks , namely lane keeping and lane changes . The LCT has been shown to reliably detect distraction from driving . As this test becomes increasingly important for the assessment of safety the validity of the LCT is crucial . In order to examine this further , the effect of an alcohol intoxication of 0.08 g/dl on the performance in the LCT was examined in the present study as the negative effects of alcohol on driving are well known . Twenty-three participants were tested under alcohol and placebo in a cross-over design measuring different performance indicators in the LCT . There were significant effects of alcohol during the lane keeping phase . However , these were much smaller than those typically found with distracting secondary tasks . The lane change phase was only marginally affected by alcohol . This result gives rise to some caution for interpreting effects in the LCT . The LCT is well able to detect distraction , as other studies have shown . However , our study with intoxicated participants shows that a small effect in the LCT does not necessarily mean that this condition does not impair driving AIMS Marketing that promotes mixing caffeinated ' energy ' drinks with alcoholic beverages ( e.g. Red Bull with vodka ) targets young drinkers and conveys the expectation that caffeine will offset the sedating effects of alcohol and enhance alertness . Such beliefs could result in unwarranted risk taking ( e.g. driving while intoxicated ) . The aim of this study was to assess the acute effects of caffeinated versus non-caffeinated alcoholic beverages on a simulated driving task and attention/reaction time . DESIGN We conducted a 2 × 2 between-groups r and omized trial in which participants were r and omized to one of four conditions : beer and non-alcoholic beer , with and without caffeine added . Caffeine was added in the same proportion as found in a commercially available caffeinated beer ( 69 mg/12 oz of beer at 4.8 % alc . by vol ) . PARTICIPANTS Participants were 127 non-dependent , heavy episodic , young adult drinkers ( age 21 - 30 ) who were college students or recent graduates . The target breath alcohol level was 0.12 g% . MEASURES Driving performance was assessed with a driving simulator ; sustained attention/reaction with the Psychomotor Vigilance Task ( PVT ) . FINDINGS Across the driving and attention/reaction time we found main effects for alcohol , with alcohol significantly impairing driving and sustained attention/reaction time , with mainly large statistical effects ; however , the addition of caffeine had no main or interaction effects on performance . CONCLUSION The addition of caffeine to alcohol does not appear to enhance driving or sustained attention/reaction time performance relative to alcohol alone Both driving speed and speed of detection of potentially hazardous events while driving have been found to correlate positively with accident rates across individuals . Alcohol ingestion is also known to increase risk of a traffic accident . This paper reports two double-blind , placebo-controlled studies : one on the effect of alcohol on driving speed and the other on the effect of alcohol on time taken to detect potential traffic hazards . Moderate drinkers aged between 30 and 55 took part . Each subject underwent three experimental conditions on separate days : no alcohol , low alcohol ( 0.025 % BAC ) and moderate alcohol ( 0.05 % BAC ) . The order of conditions was counterbalanced . The moderate alcohol dose increased mean time taken to respond to hazards ( 2.5 s in no alcohol condition compared with 3.2 s in moderate alcohol condition ) but did not affect mean driving speed ( indexed by time taken to travel sections of a fixed route ; 19.3 s in no alcohol compared with 19.0 s in moderate alcohol ) . The results support the view that at least part of the excess risk of accident associated with alcohol ingestion is attributable to an increase in the time taken to respond to traffic hazards High rates of binge drinking and alcohol-related problems , including drinking and driving , occur among college students . Underlying reasons for the heightened impaired driving rates in this demographic group are not known . The authors hypothesized that acute tolerance to the interoceptive cues of intoxication may contribute to these maladaptive decisions to drive in binge drinkers . Groups of binge-drinking and non-binge-drinking college students ( N = 28 ) attended sessions during which they received a moderate dose of alcohol ( 0.65 g/kg ) or a placebo . The development of acute tolerance to subjective ratings of intoxication and simulated driving performance was assessed by comparing measures taken during the ascending phase and descending phases of the blood alcohol curve . Compared with placebo , alcohol increased ratings of intoxication and impaired multiple aspects of simulated driving performance in both binge and non-binge drinkers . During the descending phase of the blood alcohol curve , binge drinkers showed acute tolerance to alcohol 's effect on subjective intoxication , and this effect was accompanied by an increased rating of willingness to drive . By contrast , non-binge drinkers showed no acute tolerance Changes in drivers , vehicles , and roadways pose substantial challenges to the transportation safety community . Crash records and naturalistic driving data are useful for examining the influence of past or existing technology on drivers , and the associations between risk factors and crashes . However , they are limited because causation can not be established and technology not yet installed in production vehicles can not be assessed . Driving simulators have become an increasingly widespread tool to underst and evolving and novel technologies . The ability to manipulate independent variables in a r and omized , controlled setting also provides the added benefit of identifying causal links . This paper introduces a special issue on simulator-based safety studies . The special issue comprises 25 papers that demonstrate the use of driving simulators to address pressing transportation safety problems and includes topics as diverse as neurological dysfunction , work zone design , and driver distraction This study presents an investigation of the effects of peer attitude , gender , and blood alcohol level on driving performance using a driving simulator . The subjects were 18 male and 18 female social drinkers from the general population , aged 18 - 25 , and holding a current drivers ' licence . Subjects were r and omly assigned to pro or against drinking driving conditions and tested at different blood alcohol levels . The results revealed that subjects in the for drinking driving condition perceived themselves to be more capable than they actually were and drove increasingly faster and made more mistakes than subjects in the against drinking driving condition when under the influence of alcohol . Sign Output:	Alcohol consumption mostly deteriorated the following performance outcomes in descending order : SDSD , LPSD , speed , MLPD , LC and NA . Alcohol consumption may decrease simulated driving performance in alcohol consumed people compared with non-alcohol consumed people via changes in SDSD , LPSD , speed , MLPD , LC and NA .
MS212042	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Abstract OBJECTIVE : To determine the incremental cost-effectiveness of a quality improvement depression intervention ( enhanced care ) in primary care setting s relative to usual care . DESIGN : Following stratification , we r and omized 12 primary care practice s to enhanced or usual care conditions and followed patients for 12 months . SETTING : Primary care practice s located in 10 states across the United States . PATIENTS / PARTICIPANTS : Two hundred eleven patients beginning a new treatment episode for major depression . INTERVENTIONS : Training the primary care team to assess , educate , and monitor depressed patients during the acute and continuation stages of their depression treatment episode over 1 year . MEASUREMENTS AND MAIN RESULTS : Cost-effectiveness was measured by calculating incremental ( enhanced minus usual care ) costs and quality -adjusted life years ( QALYs ) derived from SF-36 data . The mean incremental cost-effectiveness ratio in the main analysis was $ 15,463 per QALY . The mean incremental cost-effectiveness ratios for the sensitivity analyses ranged from $ 11,341 ( using geographic block variables to control for pre-intervention service utilization ) to $ 19,976 ( increasing the cost estimates by 50 % ) per QALY . CONCLUSIONS : This quality improvement depression intervention was cost-effective relative to usual care compared to cost-effectiveness ratios for common primary care interventions and commonly cited cost-effectiveness ratio thresholds for intervention implementation Abstract BACKGROUND : Major depression is common in older adults and is associated with increased health care costs . Depression often remains unrecognized in older adults , especially in primary care . OBJECTIVE : To evaluate the cost-effectiveness of a disease management program for major depression in elderly primary care patients compared with usual care . DESIGN : Economic evaluation alongside a cluster r and omized-controlled trial . PARTICIPANTS : Consecutive patients of 55 years and older were screened for depression using the Geriatric Depression Scale and the PRIME-MD was used for diagnosis . INTERVENTIONS : General practitioners in the intervention group received training on how to implement the disease management program consisting of screening , patient education , drug therapy with paroxetine , and supportive contacts . General practitioners in the usual care group were blind to the screening results . Treatment in this group was not restricted in any way . MEASUREMENTS : Severity of depression , recovery from depression , and quality of life . Re source use measured over a 12-month period using interviews and valued using st and ard costs . RESULTS : Differences in clinical outcomes between the intervention and usual care group were small and statistically insignificant . Total costs were $ 2,123 in the intervention and $ 2,259 in the usual care group ( mean difference −$136 , 95 % confidence interval : −$1,194 ; $ 1,110 ) . Cost-effectiveness planes indicated that there were no statistically significant differences in cost-effectiveness between the 2 groups . CONCLUSIONS : This disease management program for major depression in elderly primary care patients had no statistically significant relationship with clinical outcomes , costs , and cost-effectiveness . Therefore , based on these results , continuing usual care is recommended BACKGROUND General practitioners ( GPs ) can be provided with effective training in the skills to manage depression . However , it remains uncertain whether such training achieves health gain for their patients . METHOD The study aim ed to measure the health gain from training GPs in skills for the assessment and management of depression . The study design was a cluster r and omized controlled trial . GP participants were assessed for recognition of psychological disorders , attitudes to depression , prescribing patterns and experience of psychiatry and communication skills training . They were then r and omized to receive training at baseline or the end of the study . Patients selected by GPs were assessed at baseline , 3 and 12 months . The primary outcome was depression status , measured by HAM-D. Secondary outcomes were psychiatric symptoms ( GHQ-12 ) quality of life ( SF-36 ) , satisfaction with consultations , and health service use and costs . RESULTS Thirty-eight GPs were recruited and 36 ( 95 % ) completed the study . They selected 318 patients , of whom 189 ( 59 % ) were successfully recruited . At 3 months there were no significant differences between intervention and control patients on HAM-D , GHQ-12 or SF-36 . At 12 months there was a positive training effect in two domains of the SF-36 , but no differences in HAM-D , GHQ-12 or health care costs . Patients reported trained GPs as somewhat better at listening and underst and ing but not in the other aspects of satisfaction . CONCLUSIONS Although training programmes may improve GPs ' skills in managing depression , this does not appear to translate into health gain for depressed patients or the health service Abstract Objective : To assess the effectiveness of teaching general practitioners skills in brief cognitive behaviour therapy . Design : Parallel group , cluster r and omised , controlled trial of an educational package on cognitive behaviour therapy . Setting : General practice s in north London . Participants : 84 general practitioner principals and 272 patients attending their practice s who scored above the threshold for psychological distress on the hospital anxiety and depression scale . Intervention : A training package of four half days on brief cognitive behaviour therapy . Main outcome measures : Scores on the depression attitude question naire ( general practitioners ) and the Beck depression inventory ( patients ) . Results : Doctors ' knowledge of depression and attitudes towards its treatment showed no major difference between intervention and control groups after 6 months . The training had no discernible impact on patients ' outcomes . Conclusion : General practitioners may require more training and support than a basic educational package on brief cognitive behaviour therapy to acquire skills to help patients with depression . What is already known on this topic Trained professionals can deliver effective cognitive behaviour therapy to depressed patients presenting to general practitioners Limited evidence shows that cognitive behaviour therapy is effective when delivered by general practitioners who have received extensive instruction Most doctors do not have the time or inclination to carry out such comprehensive training What this study adds Basic training in brief cognitive behaviour therapy has little effect on general practitioners ' attitudes to the identification and treatment of depression or the outcome of their patients with emotional problems General practitioners may require more extensive training and support if they are to acquire skills in brief cognitive behaviour therapy that will have a positive impact on their Objectives : Screening is advocated to improve the recognition of patients with major depression in primary care . Furthermore , disease management programmes are advocated to improve the quality of care and outcome for these patients . But is screening and the subsequent implementation of a disease management programme more effective than usual care ? Methods : Review of the literature on the effects of disease management programmes that include screening for major depression in general practice . Results : Six r and omised controlled trials were identified in which the effectiveness of disease management programmes were studied in patients with major depression in primary care and compared with usual care . The majority of these , and especially the largest , showed positive effects on the recognition , diagnosis , treatment and outcome of patients . Population s in the US seem to benefit most . Conclusion : The results of disease management programmes for depression in primary care that include screening are positive and are more effective than usual care . Therefore , if preceded by screening , attention to the whole process of care for patients with major depression instead of paying attention to isolated elements of the process is justified Complex interventions , which have been shown to improve primary care depression outcomes , are difficult to disseminate to routine practice setting s. To address this problem , we developed a brief intervention to train primary care physicians and nurses employed by the practice to improve the detection and management of major depression . Before recruitment began , the research team conducted academic detailing conference calls with primary care physicians and nurses , and provided in-person training with nurses and administrative staff . Administrative staff screened over 11,000 patients before their visits to identify those with probable major depression . Primary care physicians delegated increased responsibility to office nurses , who educated over 90 % of patients about effective depression treatment and systematic ally monitored their progress over time . Early results demonstrate that community primary care practice s can rebundle traditional team roles over the short-term to provide more systematic mental health treatment without adding additional personnel . A rigorous evaluation of this effort will reduce time-consuming , expensive , and often unsuccessful efforts to " translate " research intervention findings into everyday practice Abstract Objective : To evaluate the effectiveness of a population based , multifaceted shared care intervention for late life depression in residential care . Design : R and omised controlled trial , with control and intervention groups studied one after the other and blind follow up after 9.5 months . Setting : Population of residential facility in Sydney living in self care units and hostels . Participants : 220 depressed residents aged ≥65 without severe cognitive impairment . Intervention : The shared care intervention included : ( a ) multidisciplinary consultation and collaboration , ( b ) training of general practitioners and carers in detection and management of depression , and (c)depression related health education and activity programmes for residents . The control group received routine care . Main outcome measure : Geriatric depression scale . Results : Intention to treat analysis was used . There was significantly more movement to “ less depressed ” levels of depression at follow up in the intervention than control group ( Mantel-Haenszel stratification test , P=0.0125 ) . Multiple linear regression analysis found a significant intervention effect after controlling for possible confounders , with the intervention group showing an average improvement of 1.87 points on the geriatric depression scale compared with the control group ( 95 % confidence interval 0.76 to 2.97 , P=0.0011 ) . Conclusions : The outcome of depression among elderly people in residential care can be improved by multidisciplinary collaboration , by enhancing the clinical skills of general practitioners and care staff , and by providing depression related health education and activity programmes for residents . Key messages Large numbers of depressed elderly people live in residential care but few receive appropriate management A population based , multifaceted shared care intervention for late life depression was more effective than routine care in improving depression outcome The outcome of late life depression can be improved by enhancing the clinical skills of general practitioners and care staff and by providing depression related health education and activity programmes for residents The intervention needs further refining and evaluation to improve its effectiveness and to determine how best to implement it in other residential care setting BACKGROUND Depression , a common disorder often treated by family physicians , may be both underdiagnosed and undertreated . The objective of this study was to determine whether the diagnosis and treatment of depression by family physicians could be improved through an educational strategy . METHODS In this study , conducted between July and December 1997 , 42 family physicians in Newfoundl and were r and omly assigned to an intervention group ( 3-hour case-based educational session on clinical practice guidelines [ CPGs ] for depression and access to a psychiatrist for consultation ) or to a control group ( receipt of CPGs without educational session or access to the psychiatrist ) . Physicians were asked to keep a log of patients with newly diagnosed depression and to record information on severity of depression , medications and referrals to mental health professionals . Patients were asked to complete the Centre for Epidemiologic Studies Depression ( CES-D ) scale before treatment and after 6 months of follow-up . The primary outcome measure was the " gain " score ( difference between first and last CES-D scores ) . RESULTS During the study period physicians in the intervention group diagnosed 91 new cases of depression ( mean 4.1 per physician ) and those in the control group diagnosed 56 ( mean 2.8 per physician ) ; the difference was not significant . Most patients ( 91.2 % in the intervention group and 89.3 % in the control group received a prescription for an antidepressant on their first visit . Similar proportions ( 46.2 % in the intervention group and 37.5 % in the control group ) took their medication for the full 6 months ; however , significantly more patients in the intervention group were taking an antidepressant at the 6-month follow-up ( 56 % v. 39.3 % , p = 0.02 ) . The mean number of visits per patient was similar in the 2 groups ( 7.7 in the intervention group and 7.6 in the control group ) . Physicians in the intervention group consulted the psychiatrist 9 times . The overall rate of referrals to psychiatrists and other mental health professionals was 10.9 % ; however , referrals were significantly higher in the intervention group ( 15.4 % v. 3.5 % , p = 0.05 ) . After 6 months of follow-up , a significant difference in gain scores was detected between the intervention and control groups for both the patient 's self-rated CES-D scores ( mean gain score 19.3 v. 15.5 respectively , p = 0.04 ) and the physicians ' ratings of depression severity before treatment and at 6 months ( mean gain 1.1 v. 0.7 respectively , p = 0.02 ) . INTERPRETATION The educational strategy had a modest beneficial effect on the outcomes of patients with depression , but there are still concerns regarding the low rates of drug treatment and referral to mental health professionals by family physicians PURPOSE Although potentially costly , enhancing primary care depression management on an ongoing basis results in substantial long-term treatment effectiveness . The purpose of this article is to compare the cost-effectiveness of this approach with that of usual care . METHODS The study was conducted in 12 community primary care practice s r and omized to enhanced or usual care after stratification by baseline practice patterns . Practice s assigned to enhanced care encouraged depressed patients to engage in active treatment , using practice nurses to provide regularly scheduled care management during the course of 24 months . We analyze outcomes for 211 adults ( 73.4 % of potential eligible patients ) beginning a new treatment episode for major depression determined by previsit screening . Outcomes included blinded estimates of days free of depression impairment as well as health care costs for 2 years . RESULTS Enhanced care significantly increased the number of days free of depression impairment for 2 years when compared with usual care ( 647 Output:	Training of providers alone ( even in a specific interventional method ) did not result in improved patient outcomes . The additional implementation of guidelines and the use of more complex interventions in primary care yield a significant reduction in depressive symptomatology . Provider training by itself does not seem to improve depression care ; however , if combined with additional guidelines implementation , results are promising for new-onset depression patient sample s. Additional organizational structure changes in form of collaborative care models are more likely to show effects on depression care
MS212043	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: We carried out a trial to evaluate the complication rate of intravesical ( LP ) versus extravesical ( Lich ) ureteroneocystostomy in recipients of renal transplantation . Ureteric stenosis was the predominant complication in the LP technique , which was more difficult to correct . Complications by the Lich technique were urinary leaks , which were managed successfully by prolonged bladder drainage . We conclude that the Lich technique is simpler to perform and avoids the complication of ureteric stenosis , and should therefore be the procedure of choice for ureteric implantation in recipients of renal transplants AIM To compare urological infections in patients with or without stents following transplantation and to determine the effect of such infections on graft function . METHODS All 285 recipients of kidney transplantation at our centre between 2006 and 2010 were included in the study . Detailed information including stent use and transplant function was collected prospect ively and analysed retrospectively . The diagnosis of urinary tract infection was made on the basis of compatible symptoms supported by urinalysis and /or microbiological culture . Graft function , estimated glomerular filtration rate and creatinine at 6 mo and 12 mo , immediate graft function and infection rates were compared between those with a stent or without a stent . RESULTS Overall , 196 ( 183 during initial procedure , 13 at reoperation ) patients were stented following transplantation . The overall urine leak rate was 4.3 % ( 12/277 ) with no difference between those with or without stents - 7/183 vs 5/102 , P = 0.746 . Overall , 54 % ( 99/183 ) of stented patients developed a urological infection compared to 38.1 % ( 32/84 ) of those without stents ( P = 0.0151 ) . All 18 major urological infections occurred in those with stents . The use of stent ( Wald χ(2 ) = 5.505 , P = 0.019 ) and diabetes mellitus ( Wald χ(2 ) = 5.197 , P = 0.023 ) were found to have significant influence on urological infection rates on multivariate analysis . There were no deaths or graft losses due to infection . Stenting was associated with poorer transplant function at 12 mo . CONCLUSION Stents increase the risks of urological infections and have a detrimental effect on early to medium term renal transplant function OBJECTIVE To determine whether the change from the Leadbetter-Politano technique to a stented extravesical technique for the vesico-ureteric anastomosis in renal transplantation has altered the incidence of urological complications . PATIENTS AND METHODS Data were retrieved from a prospect i ve computerized data base and by case-note review on 248 consecutive renal transplants performed between January 1990 and June 1996 . The characteristics of the donor . recipient and organ were noted , together with the technique used for the vesicoureteric anastomosis and the occurrence of major and minor urological complications . RESULTS The Leadbetter-Politano technique was used in 140 transplants and the stented extravesical technique in 108 . There were no significant differences in the donor , recipient or organ characteristics between the groups . The stented extravesical technique was associated with a significantly lower rate of major complications ( < 2 % ) and clinical ly significant haematuria than with the Leadbetter-Politano technique . CONCLUSION Changing from the Leadbetter-Politano technique to a stented extravesical technique for the vesico-ureteric anastomosis has been a major factor in reducing the incidence of urological complications in our transplant practice OBJECTIVES To evaluate the impact of the routine use of double-J stents in live-donor renal transplantation at a single institute from a prospect i ve r and omized study . METHODS A total of 100 patients were prospect ively r and omized into two groups of 50 patients each . Group 1 received a routine double-J silicone ureteral stent and group 2 did not . A st and ard Lich-Gregoir ureteroneocystostomy was performed in both groups . In group 1 , the patients were scheduled for stent removal after 2 weeks . RESULTS Both groups were comparable in terms of age , sex , ischemia time , number of renal arteries , and time to diuresis . In group 1 , two grafts were lost in the early postoperative period and those patients were excluded from the final analysis . None of our patients in either group had developed a ureteral stricture at a mean follow-up of 10.8 + /- 3.6 months . In the stented group , 2 patients developed a urinary leak , but no leakage was reported in the nonstented group ( P = 0.14 ) . Although 19 patients in group 1 ( 39.6 % ) had a urinary tract infection , only 9 in group 2 ( 18 % ) showed evidence of a positive urine culture ( P = 0.02 ) . The presence of a ureteral stent and female sex were the independent predictors of postoperative urinary tract infection on multivariate analysis . The mean serum creatinine at discharge was 1.2 + /- 0.3 mg% and 1.2 + /- 0.4 mg% in groups 1 and 2 , respectively ( P = 0.2 ) . CONCLUSIONS The results of our study have shown that routine ureteral stent insertion has no impact on the rate of vesicoureteral leakage or obstruction in live-donor renal transplantation , whereas it is significantly associated with an increased incidence of urinary tract infection . Stenting should be limited to patients with a pathologic and /or defunctionalized bladder Taguchi technique of ureteral implantation was used in 22 kidney transplant patients ( group T ) . Group T was compared with 25 patients who were treated using Lich-Gregoir technique ( group LG ) . Immunosuppression , incidence of biopsy evidence d acute cellular rejection ( ACR ) , haematuria rate and ureteral complications ( stricture , reflux ) were assessed in both groups . The immunosuppression used was based on cyclosporin A ( 63.6 % ) , tacrolimus ( 27.3 % ) and sirolimus ( 8.1 % ) in T group . Cyclosporin A ( 72 % ) , tacrolimus ( 20 % ) and sirolimus ( 8 % ) were used in LG group . No induction was used . The incidence of ACR was similar in both groups – T resp . LG was 50 % resp . 52 % . Haematuria after operation was on average 4.0 days in the T group and on average 3.1 in the LG group . Ureteral complications were observed in 18.2 % of cases in T group and in 16 % of cases in LG group . No reflux was evidence d in any group . Taguchi technique is fast and very easy to do . A slightly higher incidence of ureteral complications and a longer period of postoperative haematuria were observed in T group . Taguchi technique is very easily performed with a shorter operating time . We advocate it as a method of ureteral implantation on the thin-wall urinary bladder . The results were very good in these cases Abstract The incidence of urologic complications was studied in 131 patients with cadaver renal allografts allocated r and omly to undergo either the Politano-Leadbetter or end-to-side ureteroneocystostomy . Obstruction occurred in 6 per cent of patients with end-to-side versus 0 per cent of those with Politano-Leadbetter reconstructions ( p less than 0.05 ) . Complications of leakage , infection and graft loss were comparable in the 2 groups Background . Whether routine ureteric stenting in low-urological-risk patients reduces the risk of urological complications in kidney transplantation is not established . Methods . Eligible patients were recipients of single-organ renal transplants with normal lower urinary tracts . Patients were r and omized intraoperatively to receive either routine stenting or stenting only in the event of technical difficulties with the anastomosis . All patients underwent Lich-Gregoire ureteroneocystostomy . Results . Between June 1994 and December 1997 , 331 kidney transplants were performed at a single center , 305 patients were eligible , and 280 patients were enrolled and r and omized . Donor and recipient age , sex , donor source , whether first or subsequent grafts , ureteric length , native renal disease , and immunosuppression were similar in each group . In the no-routine-stenting group 6 of 137 patients ( 4.4 % ) received stents after r and omization for intraoperative events that in the surgeon ’s opinion required use of a stent . In an intention-to-treat analysis there was no difference between groups in the primary outcome cluster of obstruction or leak [ routine stenting 5 of 143 ( 3.5 % ) vs. no routine stenting 9 of 137 (6.6%);P = 0.23 ] , or in either of these complications analyzed separately . All urological complications were successfully managed without major morbidity . Living donor organs and shorter ureteric length ( after trimming ) were univariate risk factors for leaks , although increasing donor age was associated with obstruction . Conclusions . Routine ureteric stenting is unnecessary in kidney transplantation in patients at low risk for urological complications . Careful surgical technique with selective stenting of problematic anastomoses yields similar results Output:	There was no difference in the prevalence of ureteral strictures or vesicoureteral reflux between the various techniques . Of the three most frequently used ureterovesical anastomotic techniques , the LG technique results in fewer urological complications than the PL and U techniques
MS212044	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Antioxidant defenses are one possible mechanism for decreasing oxidative damage and its potentially negative effects on age-related bone mass . OBJECTIVE This study cross-sectionally examined whether higher dietary intakes , total intakes , and serum concentrations of antioxidants may be associated with higher bone mineral density ( BMD ) . DESIGN Total hip ( and subregions ) , spine , and total-body BMDs were measured in 11,068 women aged 50 - 79 y enrolled in the Women 's Health Initiative Observational Study and Clinical Trial at 3 clinics . Antioxidant intakes from diet ( vitamin A , retinol , beta-carotene , vitamin C , vitamin E , and selenium ) were estimated by using a self-reported food-frequency question naire . Antioxidants from supplements were estimated with an interviewer-administered question naire . A r and om subset ( n = 379 ) had serum concentrations of retinol , carotenoids , and tocopherols measured . RESULTS After adjustment for important BMD-related covariates , increasing intakes of antioxidants were not independently associated with BMD . A significant interaction effect was observed between intake of total vitamin C ( lower three-fourths compared with highest one-fourth ) and use of hormone therapy ( HT ) ( P < 0.01 ) . The beneficial effect of current HT use on femoral neck BMD appeared to be greater in women with higher concentrations of total vitamin C. This interaction was also significant for total-body ( P < 0.045 ) , spine ( P = 0.03 ) , and total-hip BMDs ( P = 0.029 ) . CONCLUSIONS Our results do not support independent associations between dietary intake , total intake , or serum concentrations of antioxidants and BMD in women participating in the Women 's Health Initiative . The extent to which HT use may interact with vitamin C intake and BMD warrants further exploration BACKGROUND Cases of enhanced anticoagulant effect in response to high-dose vitamin E supplementation have been reported among patients taking oral anticoagulants . Although a vitamin E-vitamin K interaction was proposed to underlie this effect , it has not been systematic ally investigated in adults with normal baseline coagulation status . OBJECTIVE The objective was to study the effect of 12 wk of supplementation with 1000 IU RRR-alpha-tocopherol/d on biochemical measures of vitamin K status in men and women not taking oral anticoagulants . DESIGN Vitamin K status , which was assessed with the use of plasma phylloquinone concentrations , the degree of under-gamma-carboxylation of prothrombin ( proteins induced by vitamin K absence-factor II , PIVKA-II ) , and the percentage of undercarboxylated osteocalcin ( ucOC ) , was determined in 38 men and women with rheumatoid arthritis ( study A ) and in 32 healthy men ( study B ) participating in 2 independent , 12-wk r and omized clinical trials of vitamin E supplementation ( 1000 IU/d ) . RESULTS Mean ( + /- SD ) PIVKA-II increased from 1.7 + /- 1.7 to 11.9 + /- 16.1 ng/mL ( P < 0.001 ) in study A and from 1.8 + /- 0.6 to 5.3 + /- 3.9 ng/mL ( P < 0.001 ) in study B in response to 12 wk of vitamin E supplementation . An increase in PIVKA-II is indicative of poor vitamin K status . In contrast , the other measures of vitamin K status ( ie , plasma phylloquinone concentration and percentage of ucOC ) did not change significantly in response to the supplementation . CONCLUSIONS High-dose vitamin E supplementation increased PIVKA-II in adults not receiving oral anticoagulant therapy . The clinical significance of these changes warrants further investigation , but high doses of vitamin E may antagonize vitamin K. Whether such an interaction is potentially beneficial or harmful remains to be determined Postmenopausal osteoporotic bone loss occurs mainly due to cessation of ovarian function , a condition associated with increased free radicals . Vitamin E , a lipid-soluble vitamin , is a potent antioxidant which can scavenge free radicals in the body . In this study , we investigated the effects of alpha-tocopherol and pure tocotrienol on bone microarchitecture and cellular parameters in ovariectomized rats . Three-month-old female Wistar rats were r and omly divided into ovariectomized control , sham-operated , and ovariectomized rats treated with either alpha-tocopherol or tocotrienol . Their femurs were taken at the end of the four-week study period for bone histomorphometric analysis . Ovariectomy causes bone loss in the control group as shown by reduction in both trabecular volume ( BV/TV ) and trabecular number ( Tb . N ) and an increase in trabecular separation ( Tb . S ) . The increase in osteoclast surface ( Oc . S ) and osteoblast surface ( Ob . S ) in ovariectomy indicates an increase in bone turnover rate . Treatment with either alpha-tocopherol or tocotrienol prevents the reduction in BV/TV and Tb . N as well as the increase in Tb . S , while reducing the Oc . S and increasing the Ob . S. In conclusion , the two forms of vitamin E were able to prevent bone loss due to ovariectomy . Both tocotrienol and alpha-tocopherol exert similar effects in preserving bone microarchitecture in estrogen-deficient rat model Vitamin E absorption requires the presence of fat ; however , limited information exists on the influence of fat quantity on optimal absorption . In the present study we compared the absorption of stable-isotope-labelled vitamin E following meals of varying fat content and source . In a r and omised four-way cross-over study , eight healthy individuals consumed a capsule containing 150 mg (2)H-labelled RRR-alpha-tocopheryl acetate with a test meal of toast with butter ( 17.5 g fat ) , cereal with full-fat milk ( 17.5 g fat ) , cereal with semi-skimmed milk ( 2.7 g fat ) and water ( 0 g fat ) . Blood was taken at 0 , 0.5 , 1 , 1.5 , 2 , 3 , 6 and 9 h following ingestion , chylomicrons were isolated , and (2)H-labelled alpha-tocopherol was analysed in the chylomicron and plasma sample s. There was a significant time ( P<0.001 ) and treatment effect ( P<0.001 ) in (2)H-labelled alpha-tocopherol concentration in both chylomicrons and plasma between the test meals . (2)H-labelled alpha-tocopherol concentration was significantly greater with the higher-fat toast and butter meal compared with the low-fat cereal meal or water ( P<0.001 ) , and a trend towards greater concentration compared with the high-fat cereal meal ( P=0.065 ) . There was significantly greater (2)H-labelled alpha-tocopherol concentration with the high-fat cereal meal compared with the low-fat cereal meal ( P<0.05 ) . The (2)H-labelled alpha-tocopherol concentration following either the low-fat cereal meal or water was low . These results demonstrate that both the amount of fat and the food matrix influence vitamin E absorption . These factors should be considered by consumers and for future vitamin E intervention studies It has been reported that vitamin K supplementation effectively prevents fractures and sustains bone mineral density in osteoporosis . However , there are only limited reported data concerning the association between vitamin K nutritional status and bone mineral density ( BMD ) or fractures in Japan . The objectives were to evaluate the association between plasma phylloquinone ( K1 ) or menaquinone ( MK-4 and MK-7 ) concentration and BMD or fracture in Japanese women prospect ively . A total of 379 healthy women aged 30–88 years ( mean age , 63.0 years ) were consecutively enrolled . Plasma K1 , MK-4 , MK-7 , and serum undercarboxylated osteocalcin ( ucOC ) concentrations , BMD , and incidence of vertebral fractures were evaluated . In stepwise multiple linear regression analyses , L2–4 BMD and a bone turnover marker , log K1 , concentrations were independently correlated with vertebral fracture incidence . When subjects were divided into low and high K1 groups by plasma K1 concentration , the incidence of vertebral fracture in the low K1 group ( 14.4 % ) was significantly higher than that in the high K1 group ( 4.2 % ) , and its age-adjusted RR was 3.58 ( 95 % CI , 3.26–3.93 ) . L2–4 BMD was not different between the two groups . These results suggest that subjects with vitamin K1 insufficiency in bone have increased susceptibility for vertebral fracture independently from BMD Smoking increases the concentrations of free radicals , which have been suggested to be involved in bone resorption . We examined whether the dietary intake of antioxidant vitamins may modify the increased hip fracture risk associated with smoking . We prospect ively studied 66,651 women who were 40 - 76 years of age . Forty-four of the cohort members who sustained a first hip fracture within 2 - 64 months of follow-up ( n = 247 ) and 93 out of 873 age-matched controls were current smokers . Information on diet was obtained by a vali date d food-frequency question naire . The relative risk of hip fracture for current versus never smokers was analyzed in relation to the dietary intake of antioxidant vitamins stratified into two categories ( low/high ) , where median intakes among the controls were used as cut-off points . After adjustment for major osteoporosis risk factors , the odds ratio ( OR ) for hip fracture among current smokers with a low intake of vitamin E was 3.0 ( 95 % confidence interval 1.6 - 5.4 ) and of vitamin C 3.0 ( 1.6 - 5.6 ) . In contrast , the OR decreased to 1.1 ( 0.5 - 2.4 ) and 1.4 ( 0.7 - 3.0 ) with high intakes of vitamin E and C , respectively . This effect was not seen for beta-carotene , selenium , calcium , or vitamin B6 . In current smokers with a low intake of both vitamins E and C , the OR increased to 4.9 ( 2.2 - 11.0 ) . The influence of the intake of these two antioxidant vitamins on hip fracture risk was less pronounced in former smokers . Our results suggest a role for oxidant stress in the adverse effects on the skeleton of smoking , and that an insufficient dietary intake of vitamin E and C may substantially increase the risk of hip fracture in current smokers , whereas a more adequate intake seems to be protective Recent studies have shown that estrogen ( E ) likely plays a dominant role in inhibiting bone resorption in normal elderly men . Because both E and T inhibit osteoclast development and activity , stimulate osteoclast apoptosis , and inhibit osteoblast production of IL-6 , it is unclear why T is less potent than E in inhibiting bone resorption in vivo . Osteoprotegerin ( OPG ) binds to and inactivates RANKL , the final mediator of osteoclastogenesis . In vitro , OPG production is stimulated by E , and preliminary data suggest that T has the opposite effect . Thus , we analyzed serum for OPG levels from a study in which 59 elderly men ( mean age , 68 yr ) were made acutely hypogonadal using a GnRH agonist and were also placed on an aromatase inhibitor to block conversion of and rogens to estrogens . They were studied first under conditions of physiologic E and T replacement , and then r and omized to no replacement , replacement with E alone , T alone , or both E and T. E alone result ed in an 18.6 + /- 7.9 % ( mean + /- SEM ) increase in serum OPG levels ( P < 0.05 ) , whereas T alone tended to decrease OPG levels ( by 10.0 + /- 8.5 % ; P < 0.05 compared with E alone ) . Using a two-factor ANOVA model , there was a highly significant T effect ( P = 0.006 ) on decreasing serum OPG levels . Serum TNF-alpha , IL-6 , and IL-6 soluble receptor levels increased significantly in the men who had both E and T withdrawn , and the increases in TNF-alpha and IL-6sR were absent in the men treated with either E or T. However , due to the variability in these cytokine measurements , the ANOVA models were not significant for E or T effects . Taken together , these data suggest that in vivo , T decreases OPG levels , whereas E tends to have the opposite effect . These differential effects of E vs. T on OPG production may explain , at least in part , why T has weaker effects than E on inhibiting bone resorption in vivo in humans Output:	Our review found that αTF exerted beneficial , harmful or null effects on bone formation cells . Animal studies generally showed positive effects of αTF supplementation on bone in various models of osteoporosis . However , high-dose αTF was possibly detrimental to bone in normal animals . Three possible reasons high dosage of αTF can be detrimental to bone include its interference with Vitamin K function on bone , the blocking of the entry of other Vitamin E isomers beneficial to bone , and the role of αTF as a prooxidant . However , these adverse effects have not been shown in human studies . In conclusion , αTF may have a dual role in bone health , whereby in the appropriate doses it is beneficial but in high doses it may be harmful to bone
MS212045	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The objective of this study was to assess the influence of oral contraceptives ( OCs ) on the risk of venous thromboembolism ( VTE ) in young women . A 5-year case-control study including all Danish hospitals was conducted . All women 15 - 44 years old , suffering a first ever deep venous thrombosis or a first pulmonary embolism ( PE ) during the period January 1 , 1994 , to December 30 , 1998 , were included . Controls were selected annually , 600 per year in 1994 - 1995 and 1200 per year 1996 - 1998 . Response rates for cases and controls were 87.2 % and 89.7 % , respectively . After exclusion of nonvalid diagnoses , pregnant women , and women with previous thrombotic disease , 987 cases and 4054 controls were available for analysis . A multivariate , matched analysis was performed . Controls were matched to cases within 1-year age b and s. Adjustment was made for confounding influence ( if any ) from the following variables : age , year , body mass index , length of OC use , family history of VTE , cerebral thrombosis or myocardial infa rct ion , coagulopathies , diabetes , years of schooling , and previous birth . The risk of VTE among current users of OCs was primarily influenced by duration of use , with significantly decreasing odds ratios ( OR ) over time : < 1 year , 7.0 ( 5.1 - 9.6 ) ; 1 - 5 years , 3.6 ( 2.7 - 4.8 ) ; and > 5 years , 3.1 ( 2.5 - 3.8 ) , all compared with nonusers of OCs . After adjustment for confounders , current use of OCs with second- ( levonorgestrel or norgestimate ) and third- ( desogestrel or gestodene ) generation progestins when compared with nonuse result ed in ORs for VTE of 2.9 ( 2.2 - 3.8 ) and 4.0 ( 3.2 - 4.9 ) , respectively . After adjusting for progestin types and length of use , the risk decreased significantly with decreasing estrogen dose . With 30 - 40 microg as reference , 20 and 50 microg products implied ORs of 0.6 ( 0.4 - 0.9 ) and 1.6 ( 0.9 - 2.8 ) , respectively ( p(trend ) = 0.02 ) . After correction for duration of use and differences in estrogen dose , the third/second-generation risk ratio was 1.3 ( 1.0 - 1.8 ; p < 0.05 ) . In conclusion , use of OCs was associated significantly to the risk of VTE . The risk among current users was reduced by more than 50 % during the first years of use . The risk increased more than 100 % with increasing estrogen dose , and the difference in risk between users of third- and second-generation OCs , after correction for length of use and estrogen dose , was 33 % To test the efficacy and tolerance of progestagens as contraceptives in systemic lupus erythematosus ( SLE ) , 200 mg IM norethisterone enanthate was administered to 10 patients , 0.03 mg/day oral levonorgestrel to 15 patients and they were compared with 18 control patients . There were 4 episodes of active SLE in 48 patient-months on norethisterone enantate and 6 episodes in 122 patient-months on levonorgestrel as compared with 9 episodes of active disease in 298 control patient-months ( p = ns ) . There were no pregnancies and intermenstrual bleeding led to discontinuation of medication in 30 % of patients . Progestagens may be an alternative contraceptive method in SLE Epidemiologic studies conducted in the 1960s and 1970s [ 1 - 4 ] showed an increased risk for stroke as well as myocardial infa rct ion and venoocclusive disease in women who used oral contraceptives containing more than 50 g of ethinyl estradiol . These reports spurred the development of oral contraceptive pills containing less than 50 g of ethinyl estradiol . Initial studies of cerebrovascular risk in users of low-dose oral contraceptives produced conflicting results : Some investigators found increased risks [ 5 , 6 ] , and others found no increased risk [ 7 ] . In addition , few data are available on whether the risk for stroke associated with use of low-dose oral contraceptives is influenced by the type of progestin present in these medications . In the United States , most currently available low-dose oral contraceptives contain either norethindrone-type progestins ( norethindrone , norethindrone acetate , ethynodiol diacetate , or norethynodrel ) or norgestrel-type progestins ( norgestrel or levonorgestrel ) . It has been proposed that the levonorgestrel component of oral contraceptives may offset the cardiovascular benefits that arise from the use of low doses of estrogen [ 8 , 9 ] , but little empirical research has addressed this hypothesis . A recent study [ 10 ] conducted among the members of the Northern and Southern California Kaiser Permanente medical care programs reported that the use of low-dose oral contraceptives available in the United States was not associated with an increased risk for either hemorrhagic or ischemic stroke , regardless of progestin type . In that study , past users of oral contraceptives were at reduced risk for ischemic stroke but not hemorrhagic stroke ; this finding was consistent with findings from an earlier study of cerebral thromboembolic attack [ 5 ] but differed from those in a previous study of subarachnoid hemorrhage [ 7 ] . To provide information on the occurrence of stroke among oral contraceptive users in a U.S. community , we report the results of a population -based casecontrol study done in a defined geographic region of western Washington State . Methods The source population for our study was women 18 to 44 years of age residing in King , Pierce , or Snohomish counties , Washington , between 1 July 1991 and 28 February 1995 . This represented approximately 2.2 million women-years at risk , according to population estimates provided by the State of Washington Office of Financial Management . Definition and Ascertainment of Case- Patients and Controls Eligible case- patients were women in the source population with a first diagnosis of fatal or nonfatal stroke and without a history of major coronary heart disease , such as myocardial infa rct ion , angina , or congestive heart failure . We identified potential case- patients through regular review and abstract ion of 1 ) medical records containing cerebrovascular disease discharge diagnoses at all 34 acute care hospitals within the study region and 2 ) death certificates filed at county health departments . These sources were supplemented with monthly letters sent to all neurologists , neurosurgeons , and physiatrists in the region . We defined stroke as the new , rapid onset of symptoms and signs consistent with loss of cerebral function that lasted at least 24 hours and could not be ascribed to subdural hematoma ; brain tumor ; infection ; seizure ; or other neurologic disease , such as multiple sclerosis . A neurologist review ed the records to confirm the diagnosis of stroke and to classify confirmed strokes as either arterial or venous in origin . Arterial strokes were further classified as hemorrhages , ischemic events , or other [ a category that included arterial dissections ] . Aneurysmal bleeding was defined as a hemorrhagic stroke in which the diagnostic workup or autopsy showed 1 ) blood in the subarachnoid space with or without a demonstrated aneurysm and no evidence of arteriovenous malformation or 2 ) an aneurysm with blood in other locations , such as the parenchyma or ventricles , and no evidence of arteriovenous malformation . Eligible controls were women 18 to 44 years of age who were residents of King , Pierce , or Snohomish counties during the case-diagnosis period and had no history of major coronary or cerebrovascular disease . We identified a sample of these women by using r and om-digit dialing [ 11 ] . Data Collection Participating case- patients and controls were interviewed in person by trained female interviewers who used a structured question naire that elicited information about cardiovascular risk factors . We used the reproductive calendar method and color photographs of all oral contraceptive pills marketed in the United States to help women recall date s and specific br and s of oral contraceptives used . All interview questions elicited information about the time period before each participant 's reference date , which was the date of stroke for a case-patient and a date assigned at r and om from among the potential stroke occurrence date s for a control . We also sought in-person interviews with proxy respondents for case- patients who had died or were mentally impaired . To evaluate the quality of information received from proxy respondents , we did in-person interviews with proxy respondents for case- patients who had not died and who were not mentally impaired and for a r and om one third of controls [ 12 ] . The interviews with proxy respondents contained the same questions asked of the case- patients and controls . Proxy respondents and participants were not interviewed in each other 's presence . Statistical Analysis A woman was considered to be a current user of oral contraceptives if she or her proxy reported that she had been taking these pills within a month of her reference date . She was considered to be a past user if she had used oral contraceptives but was not using them at that time . The remaining women were classified as having never used oral contraceptives . We classified current users of oral contraceptives according to whether the pill was a low-dose ( < 50 g of ethinyl estradiol ) or a high-dose ( 50 g of ethinyl estradiol ) formulation . No women reported current use of pills containing more than 50 g of ethinyl estradiol . We used unconditional logistic regression models to compute estimated odds ratios and 95 % CIs [ 13 ] . We excluded from all analyses women who were pregnant at the reference date ( 5 case- patients , 14 controls ) and women for whom information on use of oral contraceptives was missing ( 6 case- patients , 24 controls ) . Thus , 173 case- patients and 485 controls were included in the analysis . Of the case- patients , 102 were classified as having had hemorrhagic stroke , 60 were classified as having had ischemic stroke , and 11 were classified as having had other types of stroke . Sixty-nine of the hemorrhagic strokes were classified as cases of aneurysmal bleeding . In all analyses , we examined the potential confounding effect of known or suspected cerebrovascular risk factors . We initially adjusted all odds ratios for age ( in years ) , race , treated hypertension , and cigarette smoking ; we then examined whether further adjustment for other characteristics changed the estimates of association . We also conducted subanalyses in which case- patients who did not have residential telephones were excluded . To determine whether the risk for total stroke associated with oral contraceptive use varied according to other cardiovascular risk factors , we estimated odds ratios separately by age , cigarette smoking status , obesity ( body mass index 27.3 kg/m2 or < 27.3 kg/m2 ) , and among women not receiving treatment for hypertension . Results Case- Patients and Controls We identified 249 women who met the eligibility criteria for stroke : One hundred forty-one were classified as having had hemorrhagic stroke , 95 as having had ischemic stroke , 10 as having had arterial dissection , and 3 as having had venous stroke . The results of computed tomography , magnetic resonance imaging , or both were available for 92 % of patients with stroke diagnoses . Ninety-one of the 141 patients with hemorrhagic strokes were further classified as having had strokes as a result of aneurysms . Of the 198 patients who were alive and not mentally impaired as a result of their strokes , 149 ( 75.3 % ) participated in the study . Most nonparticipation was due to patient refusal ( n = 30 ) or inability to locate the patient ( n = 13 ) . For the 51 eligible patients with stroke who died or were mentally impaired as a result of the stroke , we attempted to identify and recruit proxy respondents . Through r and om-digit dialing , we completed a household census for 94.9 % of the residences contacted . Among the eligible women identified , we attempted to recruit 691 who were similar in age to the patients with stroke . Six of the potential controls were excluded because of a history of major coronary heart disease or stroke , and one was excluded because she was unable to communicate in English . Of the remaining 684 women , 526 were recruited into the study , for an estimated overall response rate of 73.0 % ( 526 684 0.949 ) . Proxy Respondents We recruited proxy respondents for 34 of the 51 patients with stroke who had died or were mentally impaired , 106 of the 149 patients with stroke who had not died and were not mentally impaired , and 160 of the 273 controls whom we had selected at r and om . Approximately 80 % of the proxy respondents for both case- patients and controls were spouses or sexual partners ( 54.3 % of proxy respondents for case- patients ; 64.4 % of proxy respondents for controls ) , mothers ( 15.7 % of proxy respondents for case- patients ; 10.0 % of proxy respondents for controls ) , or roommates or close friends ( 10.7 % of proxy respondents for case- patients ; 8 Output:	Studies did not find increased odds of VTE with POPs for contraceptive purpose s , implants or LNG-IUDs nor were there increased odds of stroke or AMI with any POCs . CONCLUSION The majority of evidence identified by this systematic review did not suggest an increase in odds for venous or arterial events with use of most POCs . Any increase in risk likely translates to a small increase in absolute numbers of thrombotic events at the population level
MS212046	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND The goal of our study was to measure the effectiveness of a home-based intervention for prevention of low birth weight with 154 high-risk , low-income black women attending a prenatal clinic in Clevel and . METHODS Based on previous research , risk was defined by clinic registration between the 17th and 28th weeks of gestation , low family functioning score , and experience of at least one stressful life event prior to registration . Optional factors included being a smoker , a low maternal weight-height ratio , being age 27 or older , and a previous premature birth . A 21-item family function screen previously vali date d in a similar population was the primary determinant of psychosocial risk . Low birth weight was defined as weight less than 2,500 g regardless of gestational age . RESULTS There was no decrease in the rate of low birth weight for women who received four home visits focusing on smoking , drug and nutrition education , support , and links with community services , compared to women who received no visits . The number of prenatal visits was significantly higher in the intervention group , but an increased number of prenatal visits did not correlate with a reduced rate of low birth weight . Despite previous research , the family function screen was not an effective predictor of low birth weight in our study . A revised equation involving a history of previous premature birth , smoking , and a low maternal weight-height ratio did predict low birth weight . CONCLUSIONS These findings question the utility of short-term psychosocial interventions for influencing low birth-weight rates in low-income black clinic population s. The family function screen was not cross vali date d. Integration of any psychosocial intervention with the routine prenatal care occurring in the obstetrical clinic is suggested for future research We assessed the effectiveness of the home-visiting system in reducing the care provided in maternity units , especially hospitalization , and attempted to establish whether this system increases women 's satisfaction with medical care . The trial involved 158 women and was conducted in four maternity units in Paris . A policy of one or two weekly visits by domiciliary midwives was compared with the usual policy of the hospitals . The study was restricted to women with moderate threatened preterm labor between 26 and 36 weeks of gestation . No decrease in the number of women hospitalized or the number of days spent in hospital was observed in the intervention group , but the number of prenatal visits to outpatient clinics was significantly smaller in the intervention than control group . Satisfaction with medical care during the episode of threatened preterm labor was much greater in the intervention group . Home visits by a midwife were considered by the women to be a better care system than numerous outpatient visits or hospitalization . Our results for medical care suggest that the introduction of the home-visiting system did not greatly alter medical practice in the maternity units , although this system had been design ed to avoid or reduce hospitalization We conducted a health technology assessment of the care of women with high-risk pregnancies in the South Wales valleys . Women in the control arm were intended to receive conventional care with st and ard midwifery visits . Women in the intervention arm received additional or longer visits and domiciliary fetal heart rate telemonitoring . Eighty-one mothers were r and omized . There were significant differences in midwifery intervention re sources between domiciliary and control groups , with the former receiving a mean of 3.7 visits lasting 33.5 min , compared with 1.4 visits lasting 12.8 min for the latter . There were slightly more spontaneous labours and fewer Caesarean sections in the domiciliary group . Maternal satisfaction and anxiety were high in both groups . Domiciliary care increased the service costs by 21.02 per woman in terms of extra midwife travel and visiting time , and by a further £ 18.38 per woman in home monitoring equipment costs . This , however , was more than offset by health service savings from fewer clinic visits ( £ 35.60 ) and fewer clinic ultrasound scans ( £ 9.01 ) . Adding the reductions in lost productivity to women and their partners ( £ 34.51 ) suggests that domiciliary care was cheaper than conventional care , even if it did not greatly reduce inpatient days ( a reduction nonetheless saving £ 184.24 ) . While clinical processes were similar in both groups , there were useful practical advantages and savings for patients and the health service from the domiciliary intervention This article presents the methodology and baseline findings of a large multicenter trial involving four countries from Latin America ( Argentina , Brazil , Cuba , and Mexico ) . The study was a r and omized , controlled , single-masked trial to investigate the impact of social support during pregnancy on perinatal outcomes . Pregnant women with gestational ages between 15 and 22 weeks were screened in health facilities in the four countries . Those presenting with one or more risk factors for having a low-birthweight baby were invited to join the trial . A total of 2235 women -- between 500 and 600 in each country -- were r and omized into an intervention ( n = 1110 ) or a control ( n = 1125 ) group . Both groups were comparable in terms of nearly all baseline variables . The intervention group received a minimum of four visits at home by a trained health worker who provided direct emotional support , health education , and an attempt to enhance the woman 's social support network . Over 90 % of all women were evaluated at 36 weeks of pregnancy and soon after delivery , and 85 % at the 40th day postpartum . The outcomes under study included intrauterine growth retardation , gestational age , perinatal and maternal morbidity and mortality , labor interventions , psychological distress and characteristics of the social support network , among others . This trial showed that it was possible to select , screen , r and omize , visit , and evaluate a large number of women in four Latin American countries using a st and ardized methodology This study examines whether an integrated behavioral intervention with proven efficacy in reducing psycho-behavioral risks ( smoking , environmental tobacco smoke exposure ( ETSE ) , depression , and intimate partner violence ( IPV ) ) in African-Americans is associated with improved pregnancy outcomes . A r and omized controlled trial targeting risks during pregnancy was conducted in the District of Columbia . African-American women were recruited if reporting at least one of the risks mentioned above . R and omization to intervention or usual care was site and risk specific . Sociodemographic , health risk and pregnancy outcome data were collected . Data on 819 women , and their singleton live born infants were analyzed using an intent-to-treat approach . Bivariate analyses preceded a reduced logistical model approach to eluci date the effect of the intervention on the reduction of prematurity and low birth weight . The incidence of low birthweight ( LBW ) was 12 % and very low birthweight ( VLBW ) was 1.6 % . Multivariate logistic regression results showed that depression was associated with LBW ( OR = 1.71 , 95 % CI = 1.12–2.62 ) . IPV was associated with preterm birth ( PTB ) and very preterm birth ( VPTB ) ( OR 1.64 , 95 % CI = 1.07–2.51 , OR = 2.94 , 95 % CI = 1.40–6.16 , respectively ) . The occurrence of VPTB was significantly reduced in the intervention compared to the usual care group ( OR = 0.42 , 95 % CI = 0.19 - 0.93 ) . Our study confirms the significant associations between multiple psycho-behavioral risks and poor pregnancy outcomes , including LBW and PTB . Our behavioral intervention with demonstrated efficacy in addressing multiple risk factors simultaneously reduced VPTB within an urban minority population A r and omized controlled trial including 2235 women at high risk of low birthweight was conducted in four Latin American institutions . The objective of this trial was to evaluate a psychosocial support intervention during pregnancy aim ed at improving perinatal health and mothers ' psychosocial conditions . The core of the intervention was four to six home visits where emotional support , counseling and strengthening of the woman 's social network was provided . Outcomes were measured at 36 weeks of pregnancy , post-partum and 40 days after delivery . The intervention was not successful in either altering women 's perception of social support and satisfaction with the reproductive experience , as well as maternal and newborn 's health care . It is concluded that although high levels of psychosocial distress during pregnancy may play an independent role in determining adverse pregnancy outcomes , this adverse effect does not appear to be ameliorated by psychosocial interventions conducted only during pregnancy , particularly those of a magnitude that can be realistically implemented ( in content and frequency ) at public care services in most developing countries OBJECTIVE : To determine whether group prenatal care improves pregnancy outcomes , psychosocial function , and patient satisfaction and to examine potential cost differences . METHODS : A multisite r and omized controlled trial was conducted at two university-affiliated hospital prenatal clinics . Pregnant women aged 14–25 years ( n=1,047 ) were r and omly assigned to either st and ard or group care . Women with medical conditions requiring individualized care were excluded from r and omization . Group participants received care in a group setting with women having the same expected delivery month . Timing and content of visits followed obstetric guidelines from week 18 through delivery . Each 2-hour prenatal care session included physical assessment , education and skills building , and support through facilitated group discussion . Structured interviews were conducted at study entry , during the third trimester , and postpartum . RESULTS : Mean age of participants was 20.4 years ; 80 % were African American . Using intent-to-treat analyses , women assigned to group care were significantly less likely to have preterm births compared with those in st and ard care : 9.8 % compared with 13.8 % , with no differences in age , parity , education , or income between study conditions . This is equivalent to a risk reduction of 33 % ( odds ratio 0.67 , 95 % confidence interval 0.44–0.99 , P=.045 ) , or 40 per 1,000 births . Effects were strengthened for African-American women : 10.0 % compared with 15.8 % ( odds ratio 0.59 , 95 % confidence interval 0.38–0.92 , P=.02 ) . Women in group sessions were less likely to have suboptimal prenatal care ( P<.01 ) , had significantly better prenatal knowledge ( P<.001 ) , felt more ready for labor and delivery ( P<.001 ) , and had greater satisfaction with care ( P<.001 ) . Breastfeeding initiation was higher in group care : 66.5 % compared with 54.6 % , P<.001 . There were no differences in birth weight nor in costs associated with prenatal care or delivery . CONCLUSION : Group prenatal care result ed in equal or improved perinatal outcomes at no added cost . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00271960 LEVEL OF EVIDENCE : OBJECTIVE To examine prenatal , maternal , and infant outcomes and costs through 1 year after delivery using a model of prenatal care for women at high risk of delivering low-birth-weight infants in which half of the prenatal care was provided in women 's homes by nurse specialists with master 's degrees . STUDY DESIGN R and omized clinical trial . PATIENTS AND METHODS A sample of 173 women ( and 194 infants ) with high-risk pregnancies ( gestational or pregestational diabetes mellitus , chronic hypertension , preterm labor , or high risk of preterm labor ) were r and omly assigned to the intervention group ( 85 women and 94 infants ) or the control group ( 88 women and 100 infants ) . Control women received usual prenatal care . Intervention women received half of their prenatal care in their homes , with teaching , counseling , telephone outreach , daily telephone availability , and a postpartum home visit by nurse specialists with physician backup . RESULTS For the full sample , mean maternal age was 27 years ; 85.5 % of women were single mothers , 36.4 % had less than a high school education , 93.6 % were African American , and 93.6 % had public health insurance , with no differences between groups on these variables . The intervention group had lower fetal/infant mortality vs the control group ( 2 vs 9 ) , 11 fewer preterm infants , more twin pregnancies carried to term ( 77.7 % vs 33.3 % ) , fewer prenatal hospitalizations ( 41 vs 49 ) , fewer infant rehospitalizations ( 18 vs 24 ) , and a savings of more than 750 total hospital days and $ 2,496,145 [ corrected ] . CONCLUSION This model of care provides a reasoned solution to improving pregnancy and infant outcomes while reducing healthcare costs OBJECTIVE : Examine frequency , timing , and reasons for maternal postpartum rehospitalizations and acute care visits 1 year postpartum after a high-risk pregnancy . STUDY DESIGN : Secondary analysis of data collected during a r and omized clinical trial of advanced practice nurses gives transitional care for women with high-risk pregnancies . The 171 women were primarily African American , never married , Medicaid eligible , diagnosed with pregestational diabetes ( 20 ) , gestational diabetes ( 23 ) , either diagnosed ( 48 ) or at risk ( 44 ) for preterm labor , and chronic hypertension ( 36 ) . RESULTS : Of the total rehospitalizations ( 17 % ) and acute care visits ( 32 % ) , over one third occurred in the first 8 weeks postpartum . Chronic hypertensives and gestational diabetics had the highest rate of Output:	While programs which offer additional support during pregnancy are unlikely to prevent the pregnancy from result ing in a low birthweight or preterm baby , they may be helpful in reducing the likelihood of antenatal hospital admission and caesarean birth
MS212047	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background —Specific treatments targeting the pathophysiology of hypertensive heart disease are lacking . As aldosterone has been implicated in the genesis of myocardial fibrosis , hypertrophy , and dysfunction , we sought to determine the effects of aldosterone antagonism on myocardial function in hypertensive patients with suspected diastolic heart failure by using sensitive quantitative echocardiographic techniques in a r and omized , double-blinded , placebo-controlled study . Methods and Results —Thirty medically treated ambulatory hypertensive patients ( 19 women , age 62±6 years ) with exertional dyspnea , ejection fraction > 50 % , and diastolic dysfunction ( E/A < 1 , E deceleration time > 250m/sec ) and without ischemia were r and omized to spironolactone 25 mg/d or placebo for 6 months . Patients were overweight ( 31±5 kg/m2 ) with reduced treadmill exercise capacity ( 6.7±2.1 METS ) . Long-axis strain rate ( SR ) , peak systolic strain , and cyclic variation of integrated backscatter ( CVIB ) were averaged from 6 walls in 3 st and ard apical views . Mean 24-hour ambulatory blood pressure at baseline ( 133±17/80±7 mm Hg ) did not change in either group . Values for SR , peak systolic strain , and CVIB were similar between groups at baseline and remained unchanged with placebo . Spironolactone therapy was associated with increases in SR ( baseline : −1.57±0.46 s−1 versus 6-months : −1.91±0.36 s−1 , P<0.01 ) , peak systolic strain ( −20.3±5.0 % versus −26.9±4.3 % , P<0.001 ) , and CVIB ( 7.4±1.7dB versus 8.6±1.7 dB , P=0.08 ) . Each parameter was significantly greater in the spironolactone group compared with placebo at 6 months ( P=0.05 , P=0.02 , and P=0.02 , respectively ) , and the increases remained significant after adjusting for baseline differences . The increase in strain was independent of changes in blood pressure with intervention . The spironolactone group also exhibited reduction in posterior wall thickness ( P=0.04 ) and a trend to reduced left atrial area ( P=0.09 ) . Conclusions —Aldosterone antagonism improves myocardial function in hypertensive heart disease Summary Since there is only scanty , indirect information about the mechanism of the hypotensive effect of spironolactone , 9 patients with essential hypertension were studied according to a r and omised double-blind , cross-over protocol . Spironolactone 100 mg b.i.d . and placebo were each given for one month and the following parameters were studied : blood pressure , heart rate , response to cold pressure and h and -grip tests , as well as blood flow in the calf and finger vessels . Flow in the calf and fingers representing muscle and skin arteries , respectively , was measured semicontinuously with an ECG-triggered venous occlusion plethysmograph . After spironolactone there was a significant decrease in the systolic and diastolic blood pressures in the supine , sitting and st and ing positions ; the sitting systolic and diastolic blood pressure decreased by ( mean ± SE ) 27±4 mm Hg ( p<0.001 ) and 11±4 mm Hg ( p<0.02 ) , respectively . No orthostatic response was observed . Heart rate remained unchanged . Blood flow through muscle and skin vessels increased in 6 out of 9 patients , and in these patients calculated vascular resistance in these areas decreased . Spironolactone did not significantly change the response of systemic blood pressure to the h and grip and cold pressure tests . The present data confirm the hypotensive properties of spironolactone and show that this effect is associated with dilatation of muscle and skin arteries in many but not in all the patients . The data do not support the hypothesis that spironolactone decreases the responsiveness of systemic blood pressure to orthosympathetic stimulation The relative blood pressure response and side effects of spironolactone ( S ) , 400 mg/day , and hydrochlorothiazide ( H ) , 100 mg/day , were evaluated in a double‐masked crossed comparison . Subjects were 24 essential hypertensives , 13 normal and 11 with low renin activity . Upright renin levels were determined in the am after 3 days of moderately low sodium diet ( < 100 mEq/day ) and at the end of each drug treatment period . The values were not revealed to one investigator until completion of the study . After 4‐week placebo control periods , either S or H was given in divided doses for 6 weeks . Blood pressure measurements and side effects were evaluated at biweekly intervals . The fall in blood pressure from control was the same for each drug and was independent of renin activity . Side effects occurred more often in patients treated with S , and H was judged superior by risk/benefit analysis . We conclude that S is no more beneficial than H in hypertensive patients with either low or normal renin activity but induces a higher incidence of adverse effects in the dose used in this study . We found no evidence for a greater effectiveness of S in low‐renin essential hypertension The effects of inhibiting angiotensin converting enzyme with perindopril and aldosterone with spironolactone were tested in hypertensive patients over fifty . Accordingly , 75 patients with mild hypertension aged 50 to 70 were r and omly divided into three groups for a double-blind 8 week comparison of the actions of placebo , 4 to 8 mg/day perindopril , and 37.5 to 75 mg/day spironolactone . Side-effects caused one patient to withdraw from placebo and one from spironolactone treatment . Mean blood pressure rose by 2.4 mm Hg after placebo but dropped by 7.4 and 8.6 after perindopril and spironolactone ( P less than .01 ) . Placebo , perindopril , and spironolactone did not alter blood glucose or plasma potassium , but induced , respectively , variations of -0.09 , 0 , and + 0.34 mmol/L in cholesterol ( P = .04 ) , and -0.02 , -0.05 , and + 0.27 mmol/L in triglycerides ( P less than .01 ) . After the three treatments , changes in angiotensin converting enzyme activity averaged -1 , -6 , and -1 mU/mL ( P less than .01 ) , in active renin -2 , + 18 , and + 28 pg/mL ( P less than .01 ) , and in aldosterone , + 15 , + 8 , and + 95 pg/mL ( P less than .01 ) . Placebo , perindopril , and spironolactone did not alter microalbuminuria , but reduced urinary kallikrein activity by 0.9 , 1.8 , and 5.4 mU/mmol creatinine ( P = .04 ) . Although short-term administration of spironolactone raised renin and aldosterone markedly and lipids moderately ( possibly because of volume contraction ) , the present results show that perindopril and spironolactone are both safe and effective for treating hypertension at the age of 50 or older Twenty-seven patients with hypertension were r and omly allocated to a 10 month crossover study . Treatment consisted of spironolactone ( 200 mg/day for 2 months ) , propranolol ( 320 mg/day for 2 months ) and combined administration of both drugs at half the dosage . Between treatment periods placebo was given for 2 months . Fourteen patients were previously untreated . The average pretreatment blood pressure for the entire group was 188/114 + /- 16/7(mean + /- st and ard deviation ) mm Hg supine and 188/118 + /- 20/9 mm Hg st and ing . Both spironolactone and propranolol reduced blood pressure significantly in both the supine and st and ing positions . Upright plasma renin activity was determined by radioimmunoassay of angiotensin I. The average initial level was 1.9 + /- 1.2 ( range 0.4 to 5.0 ) ng/ml/hr . There was a close correlation between plasma renin activity and the effects of the drugs : With increasing renin level the response to propranolol was better whereas the opposite was true for spironolactone . The combination of spironolactone and propranolol decreased the blood pressure still further in the supine and st and ing positions , irrespective of initial plasma renin activity . All patients achieved a normal supine pressure . Blood pressure and plasma renin activity returned toward pretreatment values during placebo administration . It is concluded that pretreatment levels of plasma renin activity can predict the antihypertensive response to propranolol and spironolactone . The combination of the two drugs , which have different modes of action , will effectively reduce blood pressure in hypertension . The results support the concept that the renin-angiotensin-aldo-sterone system may be involved in primary hypertension In a prospect i ve , double-blind , intraindividual , cross-over , placebo-controlled multicenter study , clinical and biochemical effects of once daily postpr and ial dose regimens of 50 , 100 , and 200 mg spironolactone were investigated in 45 out patients with primary hypertension , WHO ( World Health Organization ) Stage I-II . Each of the three active therapy periods , which were r and omly allocated to patients , were of 2 months ' duration , with intervening placebo periods , Clinical and biochemical parameters , including furosemide-stimulated plasma renin activity ( PRA ) , were recorded at regular intervals . All three spironolactone doses result ed in statistically significant blood pressure ( BP ) reductions independent of initial pretreatment levels and yielded satisfactory BP control in more than half of the patients . The 200 mg daily dose of spironolactone was found to be more effective than 50 but not 100 mg . When , correlating blood pressure response ( delta MAP ) to PRA , the profiling for positive spironolactone responders was characterized by high age and low PRA , irrespective of sex . Spironolactone therapy result ed in decreased serum sodium and magnesium values ; potassium , creatinine , urate , and triglyceride levels were increased . However , all treatment values were within normal ranges . Side effects were infrequent and mainly of endocrine nature In a crossover study 32 patients with hypertension were r and omly allocated to treatment with spironolactone 200 mg/day for two months , propranolol 320 mg/day for two months , and a combination of both drugs at half the dose . Between the treatments placebo was given for two months . Both spironolactone and propranolol lowered the blood pressure significantly in both positions . The initial plasma renin activity ( PRA ) levels ranged from 0 - 4 to 5 - 0 mug angiotensin I l-1 h-1 , and there was a close correlation between these levels and the effects of the drugs : with increasing PRA the response to propranolol was better while the opposite was true for spironolactone . Spironolactone reduced the blood pressure more at eight than at four weeks , while no such difference could be shown for propranolol . Spironolactone and propranolol together decreased the blood pressure still further irrespective of the initial PRA . All patients achieved a normal supine blood pressure Aims /hypothesisAldosterone antagonism improves endothelial function ( and reduces deaths ) in chronic heart failure . It is not known whether similar effects occur in other high-risk groups such as patients with diabetes and hypertension . We therefore assessed the full effects of aldosterone blockade in poorly controlled hypertensive patients with type 2 diabetes , focussing on blood pressure , endothelial function , glycaemic control and key hormones . Methods We performed a r and omised , placebo-controlled , double-blind , crossover study on 50 patients with type 2 diabetes and treated but poorly controlled hypertension , comparing spironolactone versus placebo . Patients had their endothelial function assessed by st and ard forearm venous occlusion plethysmography . Results There was no significant improvement in endothelium-dependent vasodilatation in response to acetylcholine , despite highly significant reductions in systolic and diastolic blood pressure . However , spironolactone significantly worsened glycaemic control , plasma angiotensin II and cortisol . Conclusions /interpretationSpironolactone is highly effective in lowering blood pressure in patients with type 2 diabetes and poorly controlled hypertension on st and ard treatment , but does not improve vascular endothelial function in this group . We speculate that any tendency for the spironolactone-induced lowering of blood pressure to improve endothelial function is offset by its tendency to worsen glycaemic control and increase the levels of angiotensin II and even possibly cortisol . Trials Registry no. : IS RCT N The long-term efficacy and tolerance of spironolactone in essential hypertension was evaluated among 20,812 patients referred to the Broussais and St. Joseph systemic hypertension clinics between 1976 and 1985 by using information prospect ively collected in the computerized ARTEMIS data bank . In 182 patients ( 51 men , 131 women ) treated with spironolactone alone during Output:	In other words , it appears that doses > 50mg/day do not produce further reductions in either SBP or DBP . From the limited available evidence , spironolactone appears to lower blood pressure compared to placebo to a similar degree in patients with primary ( essential ) hypertension when doses of 100 - 500 mg/day are given . A dose of 25 mg/day did not statistically significantly reduce systolic or diastolic blood pressure , compared to placebo . Given the lack of a dose-response , coupled with a possible increased risk in adverse events with higher doses , doses of 25 to 100 mg/day are reasonable . There is no evidence of the effect of spironolactone on clinical outcomes in hypertensive patients
MS212048	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective To evaluate the effectiveness of contemporary mammography screening using individual information about screening history and breast cancer mortality from public screening programmes . Design Prospect i ve cohort study of Norwegian women who were followed between 1986 and 2009 . Within that period ( 1995 - 2005 ) , a national mammography screening programme was gradually implemented , with biennial invitations sent to women aged 50 - 69 years . Participants All Norwegian women aged 50 - 79 between 1986 and 2009 . Main outcome measures Multiple Poisson regression analysis was used to estimate breast cancer mortality rate ratios comparing women who were invited to screening ( intention to screen ) with women who were not invited , with a clear distinction between cases of breast cancer diagnosed before ( without potential for screening effect ) and after ( with potential for screening effect ) the first invitation for screening . We took competing causes of death into account by censoring women from further follow-up who died from other causes . Based on the observed mortality reduction combined with the all cause and breast cancer specific mortality in Norway in 2009 , we used the CISNET ( Cancer Intervention and Surveillance Modeling Network ) Stanford simulation model to estimate how many women would need to be invited to biennial mammography screening in the age group 50 - 69 years to prevent one breast cancer death during their lifetime . Results During 15 193 034 person years of observation ( 1986 - 2009 ) , deaths from breast cancer occurred in 1175 women with a diagnosis after being invited to screening and 8996 women who had not been invited before diagnosis . After adjustment for age , birth cohort , county of residence , and national trends in deaths from breast cancer , the mortality rate ratio associated with being invited to mammography screening was 0.72 ( 95 % confidence interval 0.64 to 0.79 ) . To prevent one death from breast cancer , 368 ( 95 % confidence interval 266 to 508 ) women would need to be invited to screening . Conclusion Invitation to modern mammography screening may reduce deaths from breast cancer by about 28 % Background . Few prospect i ve studies have examined associations between breast cancer worry and screening behaviours in women with elevated breast cancer risks based on family history . Methods . This study included 901 high familial risk women , aged 23–71 years , from the Ontario site of the Breast Cancer Family Registry . Self-reported breast screening behaviours at year-one followup were compared between women at low ( N = 305 ) , medium ( N = 433 ) , and high ( N = 163 ) levels of baseline breast cancer worry using logistic regression . Nonlinear relationships were assessed using likelihood ratio tests . Results . A significant non-linear inverted “ U ” relationship was observed between breast cancer worry and mammography screening ( P = 0.034 ) for all women , where women at either low or high worry levels were less likely than those at medium to have a screening mammogram . A similar significant non-linear inverted “ U ” relationship was also found among all women and women at low familial risk for worry and screening clinical breast examinations ( CBEs ) . Conclusions . Medium levels of cancer worries predicted higher rates of screening mammography and CBE among high-risk women Breast cancer is the most common cancer among women globally . This study was conducted to compare the awareness of breast cancer and the practice of breast self-examination ( BSE ) , clinical breast examination ( CBE ) and mammography screening among rural females in Pahang and Perak . A cross-sectional study was carried out in five selected rural districts of Pahang and Perak . Two hundred and fifty households were r and omly selected and interviewed face to face using a semi-structured question naire . The majority of residents from both states were Malay , aged between 50 and 60 years and had a secondary level of education . Malay women aged 40 - 49 years and women with a higher level of education were significantly more aware of breast cancer ( p<0.05 ) . About half of these women practice d BSE ( 60.7 % ) and CBE ( 56.1 % ) , and 7 % had underwent mammography screening . The results of this study suggest that women in Pahang and Perak have good awareness of breast cancer and that more than half practice BSE and CBE . The women 's level of education appears to contribute to their level of knowledge and health behaviour . However , more effort is needed to encourage all women in rural areas to acquire further knowledge on breast cancer Background Breast cancer screening can reduce morbidity and mortality and improve the survival rate for this malignancy . Low participation in screening programs has been attributable to many factors including lack of knowledge . The aim of this study was to assess breast cancer screening knowledge , attitudes and practice s among women of screening age ( ≥40 years old ) in the city of Al Ain , United Arab Emirates ( UAE ) . Methods A cross-sectional survey was conducted in 2013 using the Breast Cancer Awareness Measure ( CAM ) . Four out of twelve cultural and religious community centers in Al Ain city were r and omly selected . Two hundred and forty seven women were interviewed . Chi Square test and regression analysis were used to analyze the data . Results Despite the increase in the uptake of screening modalities in our study group , a lack of knowledge about breast cancer screening is still evident . Almost half ( 44.8 % ) of women who never had a Clinical Breast Exam ( CBE ) and 44.1 % of women who never had a mammography expressed a lack of knowledge about the existence of these screening techniques . Nearly one third of the participants interpreted the presence of a breast lump incorrectly and , moreover , expressed fewer worries about the nature of the lump than would normally be expected . Conclusions The National screening program needs to be improved and directed towards more efficient and targeted utilization of re sources . Healthcare professionals play a major role in alerting women to the importance of periodic screening BACKGROUND Breast cancer is the most common type of cancer in Jordan . Current efforts are focused on annual campaigns aim ed at increasing awareness about breast cancer and encouraging women to conduct mammogram screening . In the absence of regular systematic screening for breast cancer in Jordan , there is a need to evaluate current mammography screening uptake and its predictors , assess women 's knowledge and attitudes towards breast cancer and screening mammograms and to identify barriers to this preventive service . MATERIAL S AND METHODS This cross-sectional study was conducted in six governorates in Jordan through face- to-face interviews on a r and om sample of women aged 40 to 69 years . RESULTS A total of 507 participants with mean age of 46.8±7.8 years were interviewed . There was low participation rate in early detection of breast cancer practice s. Breast self-examination , doctor examination and periodic mammography screening were reported by 34.9 % , 16.8 % and 8.6 % of study participants , respectively . Additionally 3.8 % underwent breast cancer screening at least once but not periodically , while 87.6 % had never undergone mammography screening . Reported reasons for conducting the screening were : perceived benefit ( 50 % ) ; family history of breast cancer ( 23.1 % ) ; perceived severity ( 21.2 % ) ; and advice from friend or family member ( 5.8 % ) . City residents have shown higher probability of undergoing mammogram than those who live in towns or villages . Results revealed negative perceptions and limited knowledge of study participants on breast cancer and breast cancer screening . The most commonly reported barriers for women who never underwent screening were : fear of results ( 63.8 % ) ; no support from surrounding environment ( 59.7 ) ; cost of the test ( 53.4 % ) ; and religious belief , i.e. Qadaa Wa Qadar ( 51.1 % ) . CONCLUSIONS In the absence of regular systematic screening for breast cancer in Jordan , the uptake of this preventive service is very low . It is essential for the country of Jordan to work on applying regular systematic mammography screening for breast cancer . Additionally , there is a need for improvement in the current health promotion programmes targeting breast cancer screening . Other areas that could be targeted in future initiatives in this field include access to screening in rural areas and removal of current barriers INTRODUCTION Breast cancer is the leading cancer in women today and the major challenge is late presentation then later contributes to poor outcome and high fatality rate . Mammography is effective in early detection of breast cancer and consequently significantly improves the breast cancer survival . MATERIAL S AND METHODS This cross-sectional study was used to study the knowledge and awareness towards mammogram amongst women aged 15 years old and above . A systemic r and om sampling was applied and information gathered through guided interview by using a structured question naire . RESULTS Eighty-six respondents were recruited . The mean age of respondents was 40.5 years ( SD : 15.51 ) and more than 80 % had secondary and tertiary level of education . The percentage of respondents ever performed mammogram was 10.5 % ( 95 % CI : 4.0%-17.0 % ) . The rate of correct answers was between 8.1 % and 48.8 % . Most of the respondents do not sure the answer ( 45.3%-61.6 % ) rather than wrongly answer ( 4.7%-43.0 % ) . Only about 8 % truly answer that mammogram should be done once in a life . There are 10.5 % of women cl aim ed that mammogram had no serious side effect and not a painful procedure . Nearly half of respondents ( 48.8 % ) correctly mentioned that Mammogram can detect breast cancer in early stage . CONCLUSION Only a small percentage of women ever performed mammogram and there are seriously unaware and poor knowledge pertaining to mammography screening for breast cancer among women in sub urban area . A massive health education campaign through multiple methods and agencies are needed to enhance the knowledge and awareness on mammogram Output:	Barriers to mammogram screening were lack of knowledge , embarrassment , fear of cancer diagnosis , perception that breast screening was unnecessary , lack of coping skills and pain during procedure . Mammogram screening uptake among women in selected communities were generally low .
MS212049	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Osteochondral talar defects usually affect athletic patients . The primary surgical treatment consists of arthroscopic debridement and microfracturing . Although this is mostly successful , early sport resumption is difficult to achieve , and it can take up to one year to obtain clinical improvement . Pulsed electromagnetic fields ( PEMFs ) may be effective for talar defects after arthroscopic treatment by promoting tissue healing , suppressing inflammation , and relieving pain . We hypothesize that PEMF-treatment compared to sham-treatment after arthroscopy will lead to earlier resumption of sports , and aim at 25 % increase in patients that resume sports . Methods / Design A prospect i ve , double-blind , r and omized , placebo-controlled trial ( RCT ) will be conducted in five centers throughout the Netherl and s and Belgium . 68 patients will be r and omized to either active PEMF-treatment or sham-treatment for 60 days , four hours daily . They will be followed-up for one year . The combined primary outcome measures are ( a ) the percentage of patients that resume and maintain sports , and ( b ) the time to resumption of sports , defined by the Ankle Activity Score . Secondary outcome measures include resumption of work , subjective and objective scoring systems ( American Orthopaedic Foot and Ankle Society – Ankle-Hindfoot Scale , Foot Ankle Outcome Score , Numeric Rating Scales of pain and satisfaction , EuroQol-5D ) , and computed tomography . Time to resumption of sports will be analyzed using Kaplan-Meier curves and log-rank tests . Discussion This trial will provide level-1 evidence on the effectiveness of PEMFs in the management of osteochondral ankle lesions after arthroscopy . Trial registration Netherl and s Trial Register ( NTR1636 Background R and omized trials are essential in assessing the effects of healthcare interventions and are a key component in systematic review s of effectiveness . Search ing for reports of r and omized trials in data bases is problematic due to the absence of appropriate indexing terms until the 1990s and inconsistent application of these indexing terms thereafter . Objectives The objectives of this study are to devise a search strategy for identifying reports of r and omized trials in EMBASE which are not already indexed as trials in MEDLINE and to make these reports easily accessible by including them in the Cochrane Central Register of Controlled Trials ( CENTRAL ) in The Cochrane Library , with the permission of Elsevier , the publishers of EMBASE . Methods A highly sensitive search strategy was design ed for EMBASE based on free-text and thesaurus terms which occurred frequently in the titles , abstract s , EMTREE terms ( or some combination of these ) of reports of trials indexed in EMBASE . This search strategy was run against EMBASE from 1980 to 2005 ( 1974 to 2005 for four of the terms ) and records retrieved by the search , which were not already indexed as r and omized trials in MEDLINE , were downloaded from EMBASE , printed and read . An analysis of the language of publication was conducted for the reports of trials published in 2005 ( the most recent year completed at the time of this study ) . Results Twenty-two search terms were used ( including nine which were later rejected due to poor cumulative precision ) . More than a third of a million records were downloaded and scanned and approximately 80,000 reports of trials were identified which were not already indexed as r and omized trials in MEDLINE . These are now easily identifiable in CENTRAL , in The Cochrane Library . Cumulative sensitivity ranged from 0.1 % to 60 % and cumulative precision ranged from 8 % to 61 % . The truncated term ' r and om$ ' identified 60 % of the total number of reports of trials but only 35 % of the more than 130,000 records retrieved by this term were reports of trials . The language analysis for the sample year 2005 indicated that of the 18,427 reports indexed as r and omized trials in MEDLINE , 959 ( 5 % ) were in language s other than English . The EMBASE search identified an additional 658 reports in language s other than English , of which the highest number were in Chinese ( 320 ) . Conclusion The results of the search to date have greatly increased access to reports of trials in EMBASE , especially in some language s other than English . The search strategy used was subjectively derived from a small ' gold st and ard ' set of test records and was not vali date d in an independent test set . We intend to design an objective ly-derived vali date d search strategy using logistic regression based on the frequency of occurrence of terms in the approximately 80,000 reports of r and omized trials identified compared with the frequency of these terms across the entire EMBASE data base A linear analogue for rating pain with 10 , 15 and 20 cm lines is significantly less variable than a 5 cm line ( mean error of 15 cm line is 0 - 19 % , 95 % confidence limits for the group + /- 2 % and an inood correlation between repeated ratins of a recalled pain distant in time . The variance of the rating is significantly less than the repeated rating of a r and om mark . The linear analogue rating of a constant pain stimulus is reproducible and changes in rating are likely to be real changes of opinion . Pethidine 150 mg intramuscularly had no significant effect , tested 30 minutes after the administration , on the accuracy or reproducibility of the analogue rating . A linear analogue seems a suitable method of recording the patient 's opion of a severe pain such as that of labour Background Arthroscopic examination has shown that the regenerative cartilage that appears after arthroscopic drilling for thetreatment of osteochondral lesions of the talar dome does not always cover the cartilage defect sufficiently . Hypothesis The remaining degenerative cartilage at the lesions may obstruct the healing of the articular cartilage . Study Design Prospect i ve cohort study . Methods Thirty-nine patients underwent arthroscopic drilling that kept the remaining cartilage at the lesion ( group A ) , and 30 patients underwent arthroscopic drilling that removed the remaining cartilage at the lesion ( group B ) . At 1 year after theoperation , we performed ankle arthroscopy to evaluate the cartilage condition . Results The arthroscopic findings revealed that in group A , 11 cases ( 28.2 % ) were improved , 12 cases ( 30.8 % ) wereunchanged , and 16 cases ( 41.0 % ) had deteriorated ; in group B , 27 cases ( 93.1 % ) were improved and 2 cases were unchanged . There were significant differences between group A and group B in the rate of cases whose cartilage condition was seen toimprove under arthroscopic examination ( P < 0.0001 ) . Conclusions The study shows that in the treatment of osteochondral lesions of the talar dome , the removing of the remainingdegenerative cartilage may be of some benefit in the treatment of these lesions PURPOSE The purpose of this study was to compare outcomes of chondroplasty versus microfracture versus osteochondral autologous transplantation ( OAT ) in patients with osteochondral lesions of the talus ( OLT ) . METHODS After prospect i ve sample size analysis , patients with symptomatic , recalcitrant Ferkel class 2b , 3 , and 4 OLT were r and omized to chondroplasty , microfracture , or OAT treatment groups . Outcomes were measured with use of the American Orthopaedic Foot and Ankle Society ( AOFAS ) Ankle-Hindfoot Scale ( AHS ) , the Subjective Assessment Numeric Evaluation ( SANE ) rating , Numeric Pain Intensity ( NPI ) , and magnetic resonance imaging ( MRI ) . RESULTS Eleven patients had chondroplasty , 10 ankles ( 9 patients ) had microfracture , and 12 patients had OAT . Mean time to follow-up was 53 months ( range , 24 to 119 months ) . AHS scores showed no differences at 12 and 24 months , and SANE ratings showed no differences at final follow-up . NPI was significantly lower ( P < .001 ) in chondroplasty and microfracture cases as compared with OAT at 24 hours postoperatively . Pearson 's correlation analysis demonstrated an inverse relation between microfracture and OAT groups in that better outcome was associated with smaller lesions , compared with the chondroplasty group , which revealed mixed results with no particular trend . MRI revealed incomplete fill and edema after chondroplasty or microfracture and chondral gaps after OAT . CONCLUSION Our results demonstrate no difference between chondroplasty , microfracture , and OAT with regard to AHS and SANE ratings in patients with OLT . However , NPI at 24 hours postoperatively was significantly lower in patients who had chondroplasty and microfracture . LEVEL OF EVIDENCE Level I , Therapeutic study , high- quality r and omized controlled trial with no statistically significant differences but narrow confidence interval Output:	There is insufficient evidence from r and omised trials to determine which interventions are best for osteochondral defects of the talus in adults .
MS212050	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Please cite this paper as : Sambrook A , Jack S , Cooper K. Outpatient microwave endometrial ablation : 5‐year follow‐up of a r and omised controlled trial without endometrial preparation versus st and ard day surgery with endometrial preparation . BJOG 2010;117:493–496 STUDY OBJECTIVES To determine the safety and efficacy of endometrial resection , and to provide an indicator of the operative problems and treatment outcomes . DESIGN Prospect i ve study . SETTING Academic practice tertiary care setting . PATIENTS One hundred twenty-six consecutive women undergoing endometrial resection because of menorrhagia , who wished to retain their uterus . INTERVENTION Hysteroscopic endometrial resection performed as a day procedure . MEASUREMENTS AND MAIN RESULTS In 126 women , 2 cases of uterine perforation were readily identified on the operating monitor screen ; they had no serious sequelae . Three patients had heavy uterine bleeding , which was controlled by intrauterine tamponade . No women had other serious complications . CONCLUSION Hysteroscopic endometrial resection is a safe , successful , and cost-effective treatment of menorrhagia OBJECTIVE To compare danazol and gestrinone treatment as preoperative endometrial preparation for operative hysteroscopy . DESIGN Prospect i ve , r and omized clinical study . SETTING University department of gynecological , obstetrical sciences and reproductive medicine . PATIENT(S ) One hundred thirty-five patients with endouterine pathologies ( endometrial polyps , submucous myoma , septate uterus ) . INTERVENTION(S ) Patients pretreated with gestrinone ( n = 68 ) and with danazol ( n = 67 ) underwent operative hysteroscopy . MAIN OUTCOME MEASURE(S ) Endometrial response to the medical pretreatment , side effects , procedure time , intraoperative bleeding , infusion volume , patient satisfaction . RESULT ( S ) Side effects were infrequent in both groups , though the patients ' personal satisfaction was in favor of gestrinone . The rate of endometrial response was higher for the gestrinone group ( 97.1 % vs. 83.6 % ) . Operative time ( mean + /- SD ) was 12 + /- 1.8 and 15.2 + /- 1.9 minutes for the gestrinone and danazol groups , respectively . The gestrinone group showed a lower incidence of moderate bleeding ( 3 % vs. 22.4 % ) and a lower infusion volume ( 2,100 + /- 200 mL vs. 2,400 + /- 250 mL ) . Regarding cervical dilatation time , no significant difference was found between the two groups ( 1.6 + /- 0.3 minutes vs. 1.5 + /- 0.4 minutes ) . CONCLUSION ( S ) Both treatments are good ways to prepare the endometrium for operative hysteroscopy . However , the data suggest that gestrinone pretreatment is preferable to danazol The aim of this study was to determine whether or not the use of medical pre-treatment of the endometrium improves the outcome of transcervical resection of the endometrium with regards to long-term operative outcome , histological findings and patient satisfaction . A prospect i ve r and omized trial comparing three endometrial pre-treatment agents ( danazol , medroxyprogesterone acetate or nafarelin ) with no pre-treatment was conducted . The main outcome measures were : ( i ) thickness of the endometrium and myometrium resected ; ( ii ) histological stage of the endometrium at the time of operation ; ( iii ) the presence or absence of menses and ( iv ) patient satisfaction 1 year post-operatively . Of the three pre-treatments studied , danazol produced a lower median endometrial thickness than the control , showed the greatest ability to induce atrophy of the endometrial gl and s and stroma ( not statistically significant ) and produced the highest rate of amenorrhoea ( not different to the control ) . Danazol and nafarelin produced significantly lower median endometrial thickness than no pre-treatment . There were , however , no significant differences in the rates of amenorrhoea in any of the pre-treatment groups compared with that in the control group . No improvement in clinical outcome or patient satisfaction is conferred by the use of medical pre-treatments if transcervical resection of the endometrium is performed in the proliferative phase of the menstrual cycle OBJECTIVE To investigate the management of menorrhagia in primary care and its impact on referral and hysterectomy rates . DESIGN Prospect i ve observational study . SETTING 11 general practice s from the Somerset Morbidity Project . SUBJECTS 885 women consulting their general practitioner with menorrhagia over four years . MAIN OUTCOME MEASURES Proportions of these women investigated and treated with drugs in primary care , referred to a gynaecologist and undergoing operative procedures . The relation between investigation and prescribing in primary care and referral to and surgery in secondary care . RESULTS Less than half of women had a vaginal examination ( 42 % , 95 % CI 39 % to 45 % ) , or a full blood count ( 39 % , 95 % CI 36 % to 43 % ) . Almost a quarter of women , 23 % ( 95 % CI 20 % to 26 % ) , received no drugs and 37 % ( 95 % CI 34 % to 40 % ) received norethisterone . Over a third , 38 % ( 95 % CI 34 % to 40 % ) , of women were referred , and once referred 43 % ( 95 % CI 38 % to 48 % ) of women were operated on . Women referred to a gynaecologist were significantly more likely to have received tranexamic acid and /or mefenamic acid in primary care ( chi(2)=16.4 , df=1 , p<0.001 ) . There were substantial between practice variations in management , for example in prescribing of tranexamic acid and /or mefenamic acid ( range 16 % to 72 % ) and referral to gynaecology ( range 24 % to 52 % ) . There was a significant association between high referral and high operative rates ( Spearman 's correlation coefficient=0.86 , p=0.001 ) . CONCLUSIONS Substantial differences in management exist between practice s when investigating and prescribing for menorrhagia in primary care . Rates of prescribing of effective medical treatment remain low . The decision to refer a woman impacts markedly on her chances of subsequently being operated on . Effective management in primary care may not reduce referral or hysterectomy rates In a prospect i ve study in 40 patients the pretreatment for endometrial ablation with a gestagen ( Orgametril 10 mg/die ) , danazol ( 600 mg/die ) and an injection of a GnRH-analogon ( Decapeptyl-Depot ) was compared with a control group without pretreatment . The subjective estimation of the surgeon ( endometrial thickness and depth of coagulation ) showed a sufficient pretreatment in 90 % of all cases following danazol- and GnRH-analogon-pretreatment . In 90 % of the danazol- and GnRH-analogon pretreated group the histological findings showed also an atrophic or little proliferative endometrium . In a follow up of 6 months after endometrial ablation the highest amenorrhoea-rates were reached following danazol- and GnRH-analogon pretreatment . These two regimes should be used for the pretreatment for endometrial ablation Objective To compare the effectiveness of goserelin and danazol prior to endometrial laser ablation and assess different dosage regimens This r and omized , double blind , placebo-controlled study compared the usefulness of danazol 400 mg vaginally versus 600 mg orally in women as a preoperative preparation for hysteroscopic surgery . Ninety-one fertile women were r and omly allocated to Group A ( 46 patients received 400 mg of danazol placed into the posterior vaginal fornix and three oral tablets of commercially available folic acid as a placebo ) , and Group B [ 45 women treated with 600 mg of danazol orally ( 200 mg three times daily ) and two vaginal tablets of Lactobacillus rhamnosus as a placebo ] . The patients underwent an operative hysteroscopy , transvaginal sonography , blood tests , and a histological assay . A visual analog scale ( VAS ) score to compute the degree of the surgeon 's satisfaction was used . The outcome measures were as follows : an evaluation of the changes in the endometrial thickness , the prevalence of endometrial atrophy , changes in the blood tests , any collateral effects , the degree of difficulty and view , the duration of the surgical procedure , any complications during the operative hysteroscopy and associated side effects , and the surgeon 's satisfaction with the endometrial preparation . The vaginal administration route was associated with a more pronounced effect on the endometrial thickness . Significantly more patients receiving vaginal danazol ( 45/46 ) had a hypotrophic endometrium than those receiving oral danazol ( 37/45 , P<0.01 ) . In addition , the patients receiving danazol vaginally had a shorter operating time , lower infusion volume , fewer side effects , and a higher surgeon satisfaction . Vaginal danazol adequately prepares the endometrium for an operative hysteroscopy by thinning the endometrium effectively with few side effects and little impact on the metabolic parameters OBJECTIVE To evaluate the efficacy of GnRH analogue treatment before hysteroscopic resection of submucous myomas in patients with abnormal uterine bleeding . DESIGN Multicenter , prospect i ve , r and omized , clinical study . SETTING Tertiary-care university hospitals . PATIENT(S ) Thirty-nine consecutive patients with submucous myomas grade d as G0 or G1 according to the European Society for Gynecological Endoscopy classification ( myoma size 10 - 35 mm ) . INTERVENTION(S ) Patients were r and omized to either direct surgery or 2 months of GnRH analogues before undergoing hysteroscopic resection of the submucous myoma . MAIN OUTCOME MEASURE(S ) Operating times , fluid absorption , difficulty of the operation , surgeon satisfaction with the procedure , intra- and postoperative complications , postoperative pain , and patient satisfaction were recorded . RESULT ( S ) Patients treated with GnRH analogue had significantly shorter operative times ( 15.9+/-3.1 minutes vs. 21.3+/-4.0 minutes ) and significantly reduced fluid absorption ( 378+/-137 mL vs. 566+/-199 mL ) compared with no preoperative medical treatment . Operative difficulty and overall surgeon satisfaction were significantly better in the GnRH analogue group . Patient satisfaction was similar in the two groups . CONCLUSION ( S ) GnRH analogue treatment before hysteroscopic resection of G0-G1 10 - 35 mm submucous myomas was effective in reducing operative times , fluid absorption , and difficulty of the procedure STUDY OBJECTIVE To compare the effectiveness and safety of thermal balloon ablation without pretreatment with endometrium-thinning agents compared with delayed ablation with pretreatment for women with perimenopausal menorrhagia . DESIGN Prospect i ve , r and omized , controlled trial ( Canadian Task Force classification I ) . SETTING Hospital-based ambulatory medical center . PATIENTS Thirty women age 46 to 51 years with severe enough perimenopausal menorrhagia to make them c and i date s for either hysterectomy or endometrial ablation . Two patients with submucosal myomas and six who had undergone cesarean section were included . INTERVENTIONS Thirteen patients were r and omly assigned to be treated within 30 days and received a single intramuscular administration of gonadotropin releasing hormone ( GnRH ) analog ; 17 women were allocated to be treated within 3 days of enrollment without uterine preparation . A thermal balloon was inserted transcervically under general anesthesia , and after inflation in the endometrial cavity with 5 % dextrose in water , was heated to 87 degrees C for 8 minutes . MEASUREMENTS AND MAIN RESULTS Immediate and long-term major and minor complications and success rates were analyzed . Bleeding patterns and mean duration of menstrual flow were compared between groups at 6-month follow-up . No major intraoperative or postoperative complications occurred in either group , including the women who had recently undergone hysteroscopic myomectomy or had a history of cesarean section . Minor side effects were similar in both groups , and did not exceed 5 % . Overall , at 6-month follow-up , 7 women were amenorrheic , 20 hypomenorrheic , and 3 eumenorrheic . No significant differences were noted between women treated with immediate or delayed ablation in either the distribution of bleeding patterns or days of flow per cycle ( mean + /- SEM 1.8 + /- 0.42 vs 2.1 + /- 0.75 days , respectively ) . CONCLUSION This pilot study suggests that prompt treatment of perimenopausal menorrhagia with thermal balloon endometrial ablation is as effective and safe as deferred therapy combined with GnRH analog as an endometrium-thinning agent . In light of our results , the theory that previous cesarean section and presence of small submucosal myomas constitute relative contraindications for the procedure merits further consideration . ( J Am Assoc Gynecol Laparosc 6(2): Output:	It has been suggested that these agents will reduce operating time , improve the intrauterine operating environment and reduce absorption of fluid used for intraoperative uterine cavity distension . For other intraoperative and postoperative outcomes , any differences were minimal , and no benefits of GnRHa pretreatment were noted in studies in which women underwent second-generation ablation techniques . When reported , the long-term effects of endometrial thinning agents on benefits such as postoperative amenorrhoea were reduced with time . The quality of reporting of adverse events was generally poor , but , when described in the studies , they included menopausal symptoms such as hot flushes , vaginal dryness , hirsutism , decreased libido and voice changes , as well as other side effects such as headache and weight gain . AUTHORS ' CONCLUSIONS Low- quality evidence suggests that endometrial thinning with GnRHa and danazol before hysteroscopic surgery improves operating conditions and short-term postoperative outcomes . GnRHa produced slightly more consistent endometrial thinning than was produced by danazol , although both achieved satisfactory results . The effect of these agents on longer-term postoperative outcomes was reduced with time . No benefits of GnRHa pretreatment were apparent with second-generation ablation techniques . Also , side effects were more common when these agents were used
MS212051	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The aim of this study was to investigate if cognitive behavior therapy ( CBT ) based on exposure and mindfulness exercises delivered via the Internet would be effective in treating participants with irritable bowel syndrome ( IBS ) . Participants were recruited through self-referral . Eighty-six participants were included in the study and r and omized to treatment or control condition ( an online discussion forum ) . One participant was excluded after r and omization . The main outcome measure was IBS-symptom severity and secondary measures included IBS-related quality of life , GI-specific anxiety , depression and general functioning . Participants were assessed at pre-treatment , post-treatment and 3 month follow-up ( treatment condition only ) . Four participants ( 5 % of total sample ) in the treatment condition did not participate in post-treatment assessment . Participants in the treatment condition reported a 42 % decrease and participants in the control group reported a 12 % increase in primary IBS-symptoms . Compared to the control condition , participants in the treatment group improved on all secondary outcome measures with a large between group effect size on quality of life ( Cohen 's d = 1.21 ) . We conclude that CBT-based on exposure and mindfulness delivered via the Internet can be effective in treating IBS- patients , alleviating the total burden of symptoms and increasing quality of life OBJECTIVES : Psychological and behavioral therapies are being increasingly used for symptom management in patients with irritable bowel syndrome ( IBS ) . The aims of this study were to compare two delivery modes for a comprehensive self-management ( CSM ) intervention , primarily by telephone vs. entirely in person , and to compare each with usual care ( UC ) . METHODS : Adults with IBS were recruited through community advertisement . Subjects ( N=188 ) were r and omly assigned to three groups : one in which all nine weekly CSM sessions were delivered in person , one in which six of the nine sessions were conducted over telephone , and one in which subjects received UC . Primary outcome measures were a gastrointestinal ( GI ) symptom score based on six symptoms from a daily diary and disease-specific quality of life ( QOL ) . These and other outcomes were assessed at baseline and at 3 , 6 , and 12 months after r and omization . Mixed model analyses tested for differences between the three groups in each outcome variable at the three follow-up occasions , controlling for the baseline level of each outcome . RESULTS : Both GI symptom score and QOL showed significantly greater improvement in the two CSM groups than in the UC group ( P<0.001 ) , with the magnitude of this difference being quite similar for the three follow-up time points . The two CSM groups experienced a very similar degree of improvement , and there were no statistically significant differences between the two . CONCLUSIONS : A CSM program is efficacious whether delivered primarily by telephone or totally in person , and there is no evidence that replacing six of the in-person sessions by telephone sessions reduces the efficacy of the intervention Objectives : Tenapanor is a first-in-class , small-molecule inhibitor of the gastrointestinal sodium/hydrogen exchanger NHE3 . This study assessed the efficacy and safety of tenapanor in patients with constipation-predominant irritable bowel syndrome ( IBS-C ) . Methods : In this phase 2 , double-blind study , patients with IBS-C ( Rome III criteria ) were r and omized ( 1:1:1:1 ) to receive tenapanor 5 mg , 20 mg , or 50 mg b.i.d . , or placebo b.i.d . for 12 weeks . The primary end point was the complete spontaneous bowel movement ( CSBM ) responder rate , defined as the proportion of patients reporting an increase from baseline of ≥1 CSBM/week for ≥6/12 treatment weeks . Secondary end points included abdominal symptom responder rates ( ≥30 % score improvement from baseline for ≥6/12 weeks ) and a composite responder rate ( CSBM and abdominal pain response in the same week for ≥6/12 weeks ) . Results : Overall , 356 patients were r and omized ( mean age : 45.7 years ; 86.8 % women ) and 304 completed the study . The CSBM responder rate was significantly higher in the tenapanor 50 mg b.i.d . group than in the placebo group ( 60.7 vs. 33.7 % ; P<0.001 ) , as was the composite responder rate ( 50.0 vs. 23.6 % ; P<0.001 ) . Responder rates for abdominal symptoms ( pain , discomfort , bloating , cramping , and fullness ) were significantly higher in the tenapanor 50 mg b.i.d . group than in the placebo group ( all P<0.05 ) . Diarrhea was the most frequent adverse event ( tenapanor b.i.d . : 20 mg , 12.4 % ; 50 mg , 11.2 % ) . Conclusions : Tenapanor 50 mg b.i.d . significantly increased stool frequency and reduced abdominal symptoms in patients with IBS-C. Further research into tenapanor as a potential treatment for these patients is justified Twenty patients with irritable bowel syndrome ( IBS ) were r and omly assigned either to intensive , individualized cognitive therapy ( 10 sessions over 8 weeks ) or to 8 weeks of daily gastrointestinal ( GI ) symptom monitoring . Pre- to posttreatment evaluations showed significantly ( p = .005 ) greater GI symptom reduction for those receiving cognitive therapy than for those in symptom monitoring . At posttreatment , 80 % of the cognitive therapy group showed clinical ly significant improvement , whereas only 10 % of the monitoring group showed this . Results held up well at a 3-month follow-up . Within the cognitive therapy group , GI symptom reductions correlated significantly with increases in positive and reductions in negative automatic thoughts Background The heterogeneity statistic I2 , interpreted as the percentage of variability due to heterogeneity between studies rather than sampling error , depends on precision , that is , the size of the studies included . Methods Based on a real meta- analysis , we simulate artificially ' inflating ' the sample size under the r and om effects model . For a given inflation factor M = 1 , 2 , 3 , ... and for each trial i , we create a M-inflated trial by drawing a treatment effect estimate from the r and om effects model , using si2MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi = xH8viVGI8Gi = hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY = rqGqVepae9pg0db9vqaiVgFr0xfr = xfr = xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGaem4Cam3aa0baaSqaaiabdMgaPbqaaiabikdaYaaaaaa@2FBE@/M as within-trial sampling variance . Results As precision increases , while estimates of the heterogeneity variance τ2 remain unchanged on average , estimates of I2 increase rapidly to nearly 100 % . A similar phenomenon is apparent in a sample of 157 meta-analyses . Conclusion When deciding whether or not to pool treatment estimates in a meta- analysis , the yard-stick should be the clinical relevance of any heterogeneity present . τ2 , rather than I2 , is the appropriate measure for this purpose OBJECTIVES : Two identical , phase 3 , r and omized , double‐blind , placebo‐controlled trials evaluated the efficacy and safety of plecanatide in patients with irritable bowel syndrome with constipation ( IBS‐C ) . METHODS : Adults meeting Rome III criteria for IBS‐C were r and omized ( 1:1:1 ) to placebo or plecanatide ( 3 or 6 mg ) for 12 weeks . The primary efficacy end point was the percentage of overall responders ( patients reporting ≥30 % reduction from baseline in worst abdominal pain plus an increase of ≥1 complete spontaneous bowel movement (CSBM)/week from baseline in the same week for ≥6 of 12 treatment weeks ) . Safety was assessed by adverse events ( AEs ) . RESULTS : Overall , 2189 individuals were r and omized across the two studies and 1879 completed the studies . Demographic and baseline characteristics were similar across treatment groups and between studies . The percentage of overall responders in Study 1 was 30.2 % and 29.5 % for plecanatide 3 and 6 mg , respectively , vs. 17.8 % placebo ( P < 0.001 for each dose vs. placebo ) , and in Study 2 was 21.5 % ( P = 0.009 ) and 24.0 % ( P < 0.001 ) for plecanatide 3 and 6 mg , respectively , compared to 14.2 % for placebo . The percentage of sustained efficacy responders ( overall responders plus weekly responders for ≥2 of last 4 weeks of the 12‐week treatment period ) was significantly greater for both doses of plecanatide vs. placebo across both studies . All secondary end points ( stool frequency/consistency , straining , abdominal symptoms ) showed statistically significant improvements compared with placebo . The most common AE was diarrhea ( 3 mg , 4.3 % ; 6 mg , 4.0 % ; placebo , 1.0 % ) . Discontinuation due to diarrhea was infrequent ( 3 mg , 1.2 % ; 6 mg , 1.4 % ; placebo , 0 ) . CONCLUSIONS : Plecanatide significantly improved both abdominal pain and constipation symptoms of IBS‐C with minimal associated side effects and high levels of tolerability Background and objectives : We have previously shown that hypnosis can be used to study the effect of different emotions on the motility of the gastrointestinal tract . These studies demonstrated that both anger and excitement increased colonic motility while happiness led to a reduction . The purpose of this study was to investigate the effect of hypnotically induced emotion on the visceral sensitivity of the gut . Methods : Sensory responses to balloon distension of the rectum and compliance were assessed in 20 patients with irritable bowel syndrome ( IBS ) ( aged 17–64 years ; 17 female ) diagnosed by the Rome I criteria . Patients were studied on four separate occasions in r and om order either awake ( control ) or in hypnosis , during which anger , happiness , or relaxation ( neutral emotion ) were induced . Results : Hypnotic relaxation increased the distension volume required to induce discomfort ( p=0.05 ) while anger reduced this threshold compared with relaxation ( p<0.05 ) , happiness ( p<0.01 ) , and awake conditions ( p<0.001 ) . Happiness did not further alter sensitivity from that observed during relaxation . There were no associated changes in rectal compliance or wall tension . Conclusions : Further to our previous observations on motility , this study shows that emotion can also affect an IBS patient ’s perception of rectal distension and demonstrates the critical role of the mind in modulating gastrointestinal physiology . These results emphasise how awareness of the emotional state of the patient is important when either measuring visceral sensitivity or treating IBS OBJECTIVES : Psychological treatments are considered to be useful in the irritable bowel syndrome ( IBS ) , although the evidence is based on small , often flawed trials . Although cognitive behavior therapy ( CBT ) and relaxation therapy have both been promising , we hypothesized that CBT would be superior to relaxation and st and ard care alone in IBS patients . The objective of this study was to test this assumption by comparing the effects of cognitive behavior therapy with relaxation therapy and routine clinical care alone in individuals with IBS . METHODS : Patients ( n = 105 ) with Rome I criteria for IBS were recruited from advertisement ( n = 51 ) and outpatient clinics ( n = 54 ) ; those patients with resistant IBS were not included . A r and omized controlled trial with three arms ( st and ard care for all groups plus either CBT or relaxation ) for 8 wk was conducted , which applied blinded outcome assessment s using vali date d measures with 1 yr of follow-up . The primary outcome for this study was bowel symptom severity . RESULTS : Of 105 patients at the commencement of treatment , the mean bowel symptom frequency score for the whole sample was 21.1 and at the end of treatment had fallen to 18.1 ; this persisted at the 52-wk follow-up , with a significant linear trend for scores to change over time ( F= 39.57 p < 0.001 ) . However , there were no significant differences among the three treatment conditions . Significant changes over time were found for physical functioning ( F= 4.37 , p < 0.001 ) , pain ( F= 3.12 , p < 0.05 ) , general health ( F= 2.71 , p < 0.05 ) , vitality ( F= 2.94 , p < 0.05 ) , and the social functioning scales on the Medical Outcomes Study Short Form 36 ( F= 4.08 , p < 0.05 ) ; however , all three arms showed similar improvement . There were significant reductions in anxiety , depression , and locus of control scales , but no significant differences among the treatment groups were detected . CONCLUSION : Cognitive behavior and relaxation therapy seem not to be superior to st and ard care alone in IBS CONTEXT Chronic tension-type headaches are characterized by near-daily headaches and often are difficult Output:	After completion of therapy , among trials recruiting only patients with refractory symptoms , group CBT and gut-directed hypnotherapy were more efficacious than either education and /or support or routine care , and CBT via the telephone , contingency management , CBT via the internet and dynamic psychotherapy were all superior to routine care . Several psychological therapies are efficacious for IBS , although none were superior to another . CBT-based interventions and gut-directed hypnotherapy had the largest evidence base and were the most efficacious long term .
MS212052	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Bladder and sexual dysfunction are recognized complications of mesorectal resection . Their incidence following laparoscopic surgery is unknown OBJECTIVE The aims of this study were to evaluate the safety and efficacy of laparoscopic abdominoperineal resection compared to conventional approach for surgical treatment of patients with distal rectal cancer presenting with incomplete response after chemoradiation . METHOD Twenty eight patients with distal rectal adenocarcinoma were r and omized to undergo surgical treatment by laparoscopic abdominoperineal resection or conventional approach and evaluated prospect ively . Thirteen underwent laparoscopic abdominoperineal resection and 15 conventional approach . RESULTS There was no significant difference ( p<0,05 ) between the two studied groups regarding : gender , age , body mass index , patients with previous abdominal surgeries , intra and post operative complications , need for blood transfusion , hospital stay after surgery , length of resected segment and pathological staging . Mean operation time was 228 minutes for the laparoscopic abdominoperineal resection versus 284 minutes for the conventional approach ( p=0.04 ) . Mean anesthesia duration was shorter ( p=0.03 ) for laparoscopic abdominoperineal resection when compared to conventional approach : 304 and 362 minutes , respectively . There was no need for conversion to open approach in this series . After a mean follow-up of 47.2 months and with the exclusion of two patients in the conventional abdominoperineal resection who presented with unsuspected synchronic metastasis during surgery , local recurrence was observed in two patients in the conventional group and in none in the laparoscopic group . CONCLUSIONS We conclude that laparoscopic abdominoperineal resection is feasible , similar to conventional approach concerning surgery duration , intra operative morbidity , blood requirements and post operative morbidity . Larger number of cases and an extended follow-up are required to adequate evaluation of oncological results for patients undergoing laparoscopic abdominoperineal resection after chemoradiation for radical treatment of distal rectal cancer PURPOSE : Traumatic manipulation of cancer specimens during laparoscopic colectomy may increase exfoliation of malignant cells into the peritoneal cavity , causing an early occurrence of peritoneal carcinomatosis or port-sites recurrence . Because of this concern , the routine use of intraperitoneal chemotherapy after laparoscopic colectomy for cancer was suggested recently . We assessed if laparoscopicvs . conventional surgery increases exfoliated malignant cells in the peritoneal cavity during resection of colorectal cancer . METHODS : In a prospect i ve , r and omized fashion , 38 colorectal cancer patients undergoing an elective , curative operation were assigned to either a conventional or laparoscopic procedure between June 1996 and May 1997 . In either group ( n=19 ) , after the abdominal cavity was entered , saline was instilled into the peritoneal cavity , and the fluid was collected ( Specimen 1 ) . During surgery , all irrigating fluids were collected ( Specimen 2 ) . Both specimens were assessed for malignancy using four techniques : filtration process ( ThinPrep ® ) , smear , cell block , and immunochemistry using Ber-EP4 . The change in the amount of tumor cells in both specimens was compared between surgical groups . A pilot study was performed to vali date the proposed cytologic method . RESULTS : In the pilot study of 20 consecutive patients with colorectal cancer , postresectional peritoneal cytology was positive in six patients , including two Stage II ( T3,N0,M0 ) patients . The pilot study also vali date d that our semiquantitative scoring system can be reliably used to assess the amount of free peritoneal cancer cells . In the main study , 16 right colectomies , 3 extended right colectomies , 17 proctosigmoidectomies , and 1 left colectomy were performed . The T and N stages were T1 ( n=13 ) , T2 ( n=5 ) , T3 ( n=8 ) , T4 ( n=11 ) ; N0 ( n=22 ) , N1 ( n=8 ) , N2 ( n=7 ) . Malignant cells were not detected in any Specimens 1 or , more importantly , in Specimens 2 in either surgical group . CONCLUSION : When performed according to strict oncologic surgical principles , laparoscopic techniques in curative colorectal cancer surgery did not have an increased risk of intraperitoneal cancer cell spillage , compared with conventional techniques . We hope that these results can decrease some of the concerns about tumors cell spillage and seeding during laparoscopy Background and aims Evidence demonstrating improved short-term outcomes with laparoscopic surgery compared with open surgery for colorectal cancer is accumulating . In addition , programmes optimising peri-operative care for major abdominal surgery are becoming widespread . Evaluating laparoscopic surgery and enhanced recovery programmes usually focuses on short-term recovery . The aim of this study was to compare recovery after laparoscopic and open surgery for colorectal cancer up to 1 year post-operatively , using a combination of self-report and observer data . Patients / Methods From January 2002 to March 2004 , 62 patients were r and omised ( 2:1 ) to receive laparoscopic ( n = 43 ) or open surgery ( n = 19 ) within an enhanced recovery programme . Functional outcomes up to 1 year were assessed using interview-administered question naires . Results / Findings Question naire and health-related quality of life data were obtained in over 85 % of patients . Patients undergoing laparoscopic surgery felt fully recovered and resumed driving more quickly than those having open surgery ( p = 0.016 and p = 0.048 respectively ) . Fifty-eight percent of patients having open surgery felt fully recovered by 12 months versus 88 % of laparoscopic patients .Interpretation/ Conclusion Within an enhanced recovery programme , patients undergoing laparoscopic surgery recovered more quickly than after open resection . Both approaches however , were associated with slow recovery despite a relatively short hospital stay Purpose This study was design ed to evaluate the impact of laparoscopic rectal resection on short-term postoperative morbidity and costs . Methods A total of 168 patients with rectal cancer were r and omly assigned to laparoscopic ( n = 83 ) or open ( n = 85 ) resection . Outcome parameters were : postoperative morbidity , length of hospital stay , quality of life , long-term survival , and local recurrences . The mean follow-up period was 53.6 months . Cost-benefit analysis was based on hospital costs . Results Operative time was 53 minutes longer in the laparoscopic group ( P < 0.0001 ) . Postoperative morbidity rate was 28.9 percent in the laparoscopic vs. 40 percent in the open group ( P = 0.18 ) . The mean length of hospital stay was 10 ( 4.9 ) days in the laparoscopic group and 13.6 ( 10 ) days in the open group ( P = 0.004 ) . Local recurrence rate and five-year survival were similar in both groups ; however , the limited number of patients does not allow firm conclusions . Quality of life was better in the laparoscopic group only in the first year after surgery ( P < 0.0001 ) . The additional charge in the laparoscopic group was $ 1,748 per patient r and omized ( $ 1,194 the result of surgical instruments and $ 554 the result of longer operative time ) . The saving in the laparoscopic group was $ 1,396 per patient r and omized ( $ 647 the result of shorter length of hospital stay and $ 749 the result of the lower cost of postoperative complications ) . The net balance result ed in $ 351 extra cost per patient r and omly allocated to the laparoscopic group . Conclusions Short-term postoperative morbidity was similar in the two groups . Laparoscopic resection reduced length of hospital stay , improved first-year quality of life , and slightly increased hospital costs A r and omized controlled trial was started in Japan to evaluate whether laparoscopic surgery is the optimal treatment for colorectal cancer . Patients with T3 or deeper carcinoma in the colorectum without transverse and descending colons are pre-operatively r and omized to either open or laparoscopic colorectal resection . Surgeons in 24 specialized institutions will recruit 818 patients . The primary end-point is overall survival . Secondary end-points are relapse-free survival , short-term clinical outcome , adverse events , the proportion of conversion from laparoscopic surgery to open surgery , and the proportion of completion of laparoscopic surgery Laparoscopic surgery is believed to produce an attenuated metabolic stress response and to have a less dampening effect on the immune response than open surgery . To date , the effect has not been studied in a r and omized clinical trial of colorectal cancer PURPOSE : The aim of this study was to compare the safety and efficacy of laparoscopic abdominoperineal resection and open abdominoperineal resection for cancer . METHODS : Records of 194 patients who underwent laparoscopic abdominoperineal resection ( 42 patients ) or open abdominoperineal resection ( 152 patients ) at three institutions between 1991 and 1997 were review ed . Follow-up was through office charts , American College of Surgeons cancer registry , or telephone contact . Tumors included ( laparoscopic abdominoperineal resection and open abdominoperineal resection , respectively ) adenocarcinoma ( 86 and 92 percent ) , squamous ( 12 and 7 percent ) , and gastrointestinal stromal ( 2 and 1.4 percent ) types ; Stages I ( 17 and 26 percent ) , II ( 24 and 33 percent ) , III ( 43 and 32 percent ) , and IV ( 14 and 9 percent ) ; and those with invasion of pelvic structures ( 14 and 16 percent ) . RESULTS : Laparoscopic abdominoperineal resection was converted to open abdominoperineal resection in 21 percent because of vessel injury ( 33 percent ) , poor exposure ( 22 percent ) , adhesions ( 22 percent ) , inguinal hernia ( 11 percent ) , or radiation fibrosis ( 11 percent ) . Perineal infections occurred more often in the laparoscopic abdominoperineal resection group ( 24vs . 8 percent;P=0.02 ) . Late stoma complications were similar . Mean hospital stay was shorter after laparoscopic abdominoperineal resection ( 7vs . 12 days ) . Radial margins were positive in 12 percent of laparoscopic abdominoperineal resection and 12.5 percent of open abdominoperineal resection specimens . Tumor recurrence was similar for both local ( 19 and 14 percent ) and distant ( 38 and 26 percent ) recurrence . Survival rates were similar by Kaplan-Meier curves , with median follow-up of 19 and 24 months , respectively ( P=0.22 ; log rank ) . CONCLUSION : Laparoscopic abdominoperineal resection can be performed safely and results in a shorter hospital stay . A r and omized , prospect i ve trial is needed to determine the long-term outcome of cancer treatment The short-term clinical results of the CLASICC trial indicated that clinical outcomes were similar between laparoscopic and open approaches . This study presents the short-term ( 3 month ) cost analysis undertaken on a subset of patients entered into the CLASICC trial ( 682 of 794 patients ) . As expected the costs associated with the operation were higher in the 452 patients r and omised to laparoscopic surgery ( lap ) compared with the 230 r and omised to open procedure ( open ) , £ 1703 vs £ 1386 . This was partially offset by the other hospital ( nontheatre ) costs , which were lower in the lap group ( £ 2930 vs £ 3176 ) . The average cost to individuals for reoperations was higher in the lap group ( £ 762 vs £ 553 ) . Overall costs were slightly higher in the lap group ( £ 6899 vs £ 6631 ) , with mean difference of £ 268 ( 95%CI −689 to 1457 ) . Sensitivity analysis made little difference to these results . The cost of rectal surgery was higher than for colon , for lap ( £ 8259 vs £ 5586 ) and open procedures ( £ 7820 vs £ 5503 ) . The short-term cost analysis for the CLASICC trial indicates that the costs of either laparoscopic or open procedure were similar , lap surgery costing marginally more on average than open surgery Background : Laparoscopic resection of the rectum is still under scrutiny for its adequacy of oncological clearance . Aim : To assess lymph node yield after laparoscopic total mesorectal excision ( TME ) for rectal cancer as compared to the open approach . Methods : 74 patients with middle and low rectal cancer were prospect ively r and omized in two groups . Group A included 39 patients who had an open TME ( 35 with low anterior resection of the rectum ( LARR ) and 4 with abdominoperineal resection of the rectum ( APR ) ) . In group B , there were 34 patients who had a laparoscopic TME ( 27 with LARR and 7 with APR ) . 10 of the LARR patients in group A and 14 of the LAR Output:	There is evidence that LTME results in less blood loss , quicker return to normal diet , less pain , less narcotic use and less immune response . It seems likely that LTME is associated with longer operative time and higher costs . Based on evidence mainly from non-r and omized studies , LTME appears to have clinical ly measurable short-term advantages in patients with primary resectable rectal cancer .
MS212053	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Mobile devices are a promising channel for delivering just-in-time guidance and support for improving key daily health behaviors . Despite an explosion of mobile phone applications aim ed at physical activity and other health behaviors , few have been based on theoretically derived constructs and empirical evidence . Eighty adults ages 45 years and older who were insufficiently physically active , engaged in prolonged daily sitting , and were new to smartphone technology , participated in iterative design development and feasibility testing of three daily activity smartphone applications based on motivational frames drawn from behavioral science theory and evidence . An “ analytically ” framed custom application focused on personalized goal setting , self-monitoring , and active problem solving around barriers to behavior change . A “ socially ” framed custom application focused on social comparisons , norms , and support . An “ affectively ” framed custom application focused on operant conditioning principles of reinforcement scheduling and emotional transference to an avatar , whose movements and behaviors reflected the physical activity and sedentary levels of the user . To explore the applications ' initial efficacy in changing regular physical activity and leisure-time sitting , behavioral changes were assessed across eight weeks in 68 participants using the CHAMPS physical activity question naire and the Australian sedentary behavior question naire . User acceptability of and satisfaction with the applications was explored via a post-intervention user survey . The results indicated that the three applications were sufficiently robust to significantly improve regular moderate-to-vigorous intensity physical activity and decrease leisure-time sitting during the 8-week behavioral adoption period . Acceptability of the applications was confirmed in the post-intervention surveys for this sample of midlife and older adults new to smartphone technology . Preliminary data exploring sustained use of the applications across a longer time period yielded promising results . The results support further systematic investigation of the efficacy of the applications for changing these key health-promoting behaviors Background Reaction time , coordination , and cognition performance typically diminish in older adults , which may lead to gait impairments , falls , and injuries . Regular strength – balance exercises are highly recommended to reduce this problem and to improve health , well-being , and independence in old age . However , many older people face a lack of motivation in addition to other strong barriers to exercise . We developed ActiveLifestyle , an information technology (IT)-based system for active and healthy aging aim ing at improving balance and strength . ActiveLifestyle is a training app that runs on a tablet and assists , monitors , and motivates older people to follow personalized training plans autonomously at home . Objective The objectives were to ( 1 ) investigate which IT-mediated motivation strategies increase adherence to physical exercise training plans in older people , ( 2 ) assess the impact of ActiveLifestyle on physical activity behavior change , and ( 3 ) demonstrate the effectiveness of the ActiveLifestyle training to improve gait speed . Methods A total of 44 older adults followed personalized , 12-week strength and balance training plans . All participants performed the exercises autonomously at home . Question naires were used to assess the technological familiarity and stage of behavior change , as well as the effectiveness of the motivation instruments adopted by ActiveLifestyle . Adherence to the exercise plan was evaluated using performance data collected by the app and through information given by the participants during the study . Pretests and posttests were performed to evaluate gait speed of the participants before and after the study . Results Participants were 75 years ( SD 6 ) , predominantly female ( 64 % ) , held a trade or professional diploma ( 54 % ) , and their past profession was in a sitting position ( 43 % ) . Of the 44 participants who enrolled , 33 ( 75 % ) completed the study . The app proved to assist and motivate independently living and healthy older adults to autonomously perform strength – balance exercises ( median 6 on a 7-point Likert scale ) . Social motivation strategies proved more effective than individual strategies to stimulate the participants to comply with the training plan , as well as to change their behavior permanently toward a more physically active lifestyle . The exercises were effective to improve preferred and fast gait speed . Conclusions ActiveLifestyle assisted and motivated independently living and healthy older people to autonomously perform strength – balance exercises over 12 weeks and had low dropout rates . The social motivation strategies were more effective to stimulate the participants to comply with the training plan and remain on the intervention . The adoption of assistive technology devices for physical intervention tends to motivate and retain older people exercising for longer periods of time Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Background This study provides insight into the long-term efficacy ( i.e. 12 month results ) of the Web-based or print-delivered tailored Active Plus intervention ( with and without environmental approach ) to promote physical activity ( PA ) among the over-fifties . Differences in effect among subgroups are studied as well . Methods Intervention groups ( i.e. print-delivered basic ( PB ; N = 439 ) , print-delivered environmental ( PE ; N = 435 ) , Web-based basic ( WB ; N = 423 ) , Web-based environmental ( WE ; N = 432 ) ) and a waiting list control group ( N = 411 ) were studied in a clustered r and omized controlled trial . Intervention participants received tailored advice three times within 4 months . Long-term effects ( 12 months after the intervention has started , i.e. 8 months after the intervention was completed ) on PA ( i.e. self-reported weekly minutes and days of sufficient PA ) were tested using multilevel linear regression analyses . Participants ’ age , gender , BMI , educational level , PA intention and the presence of a chronic physical limitation were considered to be potential moderators of the effect . Results Overall , the Active Plus intervention was effective in increasing weekly days of sufficient PA ( B=0.49 ; p=.005 ) , but ineffective in increasing weekly minutes of PA ( B=84.59 ; p=.071 ) . Per intervention condition analysis showed that the PB-intervention ( Bdays=0.64 ; p=.002 ; Bmi n=111.36 ; p=.017 ) and the PE-intervention ( Bdays=0.70 ; p=.001 ; Bmi n=157.41 ; p=.001 ) were effective in increasing days and minutes of PA . Neither Web-based conditions significantly increased PA , while the control group decreased their PA . In contrast to the intervention effect on minutes of PA , the effect on weekly days of PA was significantly moderated by the participants ’ baseline intention to be sufficiently physically active . Conclusions In general , after 12 months the print-delivered interventions result ed in stronger effects than the Web-based interventions . The participants ’ baseline intention was the only significant moderator of the intervention effect . All other assessed user characteristics did not significantly moderate the effect of the intervention , which might indicate that the intervention is sufficiently tailored to the different participant characteristics . Additional efforts should be taken to increase the sustainability of Web-based interventions .Trial registration Dutch Trial Register : NTR2297 With more social support and environment-centered interventions being recommended in web-based interventions , this study examined the efficacy of three intervention conditions aim ed at promoting physical activity ( PA ) in older adults . The efficacy analyses included the self-reported PA level , stage of change for PA and awareness about PA among participants . Eligible participants ( N = 149 ; M = 65 years old , SD = 6 ) , recruited in a unique Belgian French-speaking municipality , were r and omized in four research arms for a 3-month intervention : ( i ) web-based ; ( ii ) center-based ; ( iii ) mixed ( combination of web- and center-based ) ; and ( iv ) control ( no intervention ) . Web-based condition included a PA website and monthly tailored emails whereas center-based condition comprised 12 sessions ( 1 per week ) of group exercising . With a significant increase in PA , the PA stage of change and the PA awareness at 12 months , the mixed intervention condition seemed to include the key social and motivating elements for sustainable behavior change . Center-based intervention was more likely to produce significant improvements of the PA level and the stage of change for PA change whereas web-based intervention was more likely to extend the awareness about PA BACKGROUND Remote and web 2.0 interventions for promoting physical activity ( PA ) are becoming increasingly popular but their ability to achieve long term changes are unknown . OBJECTIVES To compare the effectiveness of remote and web 2.0 interventions for PA promotion in community dwelling adults ( aged 16 years and above ) with a control group exposed to placebo or no or minimal intervention . SEARCH METHODS We search ed CENTRAL , MEDLINE , EMBASE , CINAHL , and some other data bases ( from earliest date s available to October 2012 ) . Reference lists of relevant articles were checked . No language restrictions were applied . SELECTION CRITERIA R and omised controlled trials ( RCTs ) that compared remote and web 2.0 PA interventions for community dwelling adults with a placebo or no or minimal intervention control group . We included studies if the principal component of the intervention was delivered using remote or web 2.0 technologies ( for example the internet , smart phones ) or more traditional methods ( for example telephone , mail-outs ) , or both . To assess behavioural change over time , the included studies had a minimum of 12 months follow-up from the start of the intervention to the final results . We excluded studies that had more than a 20 % loss to follow-up if they did not apply an intention-to-treat analysis . DATA COLLECTION AND ANALYSIS At least two authors independently assessed the quality of each study and extracted the data . Non-English language papers were review ed with the assistance of an interpreter who was an epidemiologist . Study authors were contacted for additional information where necessary . St and ardised mean differences ( SMDs ) and 95 % confidence intervals ( CIs ) were calculated for the continuous measures of self-reported PA and cardio-respiratory fitness . For studies with dichotomous outcomes , odds ratios and 95 % CIs were calculated . MAIN RESULTS A total of 11 studies recruiting 5862 apparently healthy adults met the inclusion criteria . All of the studies took place in high-income countries . The effect of the interventions on cardiovascular fitness at one year ( two studies ; 444 participants ) was positive and moderate with significant heterogeneity of the observed effects ( SMD 0.40 ; 95 % CI 0.04 to 0.76 ; high quality evidence ) . The effect of the interventions on self-reported PA at one year ( nine studies ; 4547 participants ) was positive and moderate ( SMD 0.20 ; 95 % CI 0.11 to 0.28 ; moderate quality evidence ) with heterogeneity ( I2 = 37 % ) in the observed effects . One study reported positive results at two years ( SMD 0.20 ; 95 % CI 0.08 to 0.32 ; moderate quality evidence ) . When studies were stratified by risk of bias , the studies at low risk of bias ( eight studies ; 3403 participants ) had an increased effect ( SMD 0.28 ; 95 % CI 0.16 to 0.40 ; moderate quality evidence ) . The most effective interventions applied a tailored approach to the type of PA and used telephone contact to provide feedback and to support changes in PA levels . There was no evidence of an increased risk of adverse events ( seven studies ; 2892 participants ) . Risk of bias was assessed as low ( eight studies ; 3060 participants ) or moderate ( three studies ; 2677 participants ) . There were no differences in effectiveness between studies using different types of professionals delivering the intervention ( for example health professional , exercise specialist ) . There was no difference in pooled estimates between studies that generated the prescribed PA using an automated computer programme versus a human , nor between studies that used pedometers as part of their intervention compared to studies that did not . AUTHORS ' CONCLUSIONS We found consistent evidence to support the effectiveness of remote and web 2.0 interventions for promoting PA . These interventions have positive , moderate sized effects on increasing self-reported PA and measured cardio-respiratory fitness , at least at 12 months . The effectiveness of these interventions was supported by moderate and high quality studies . However , there continues to be a paucity of cost effectiveness data and studies that include participants from varying socioeconomic or ethnic groups . To better underst and the independent effect of individual programme components , longer term studies , with at least one year follow-up , are required Output:	The results of this review will provide new information regarding the question whether eHealth interventions are an effective intervention vehicle for PA promotion in this population .
MS212054	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Obesity has become a global public health problem , which also affects children . It has been proposed that the educational interventions during childhood could be a key strategy in the prevention of obesity . Objective To evaluate the efficacy of an intervention on food habits and physical activity in school children . Methods A 2-year cluster-r and omised prospect i ve study with two parallel arms was used to evaluate an intervention programme in children in their first year of primary schooling ( 5–6 years of age ) in schools in the city of Granollers . The intervention consisted of the promotion of healthy eating habits and physical activity by means of the educational methodology Investigation , Vision , Action and Change ( IVAC ) . At the beginning and at the end of the study ( 2006 and 2008 ) the weight and height of each child was measured in situ , while the families were given a self-report physical activity question naire and the Krece Plus quick test . Results Two years after the beginning of the study , the body mass index of the children in the control group was 0.89 kg/m2 higher than that of the intervention schools . The intervention reduced by 62 % the prevalence of overweight children . Similarly , the proportion of children that ate a second piece of fruit and took part in an after-school physical activity increased in the intervention group . In the control group , the weekly consumption of fish was reduced . Conclusions The educational intervention in healthy eating habits and physical activity in the school could contribute to lessen the current increase in child obesity Objective To compare the effectiveness of classroom based cognitive behavioural therapy with attention control and usual school provision for adolescents at high risk of depression . Design Three arm parallel cluster r and omised controlled trial . Setting Eight UK secondary schools . Participants Adolescents ( n=5030 ) aged 12 - 16 years in school year groups 8 - 11 . Year groups were r and omly assigned on a 1:1:1 ratio to cognitive behavioural therapy , attention control , or usual school provision . Allocation was balanced by school , year , number of students and classes , frequency of lessons , and timetabling . Participants were not blinded to treatment allocation . Interventions Cognitive behavioural therapy , attention control , and usual school provision provided in classes to all eligible participants . Main outcome measures Outcomes were collected by self completed question naire administered by research ers . The primary outcome was symptoms of depression assessed at 12 months by the short mood and feelings question naire among those identified at baseline as being at high risk of depression . Secondary outcomes included negative thinking , self worth , and anxiety . Analyses were undertaken on an intention to treat basis and accounted for the clustered nature of the design . Results 1064 ( 21.2 % ) adolescents were identified at high risk of depression : 392 in the classroom based cognitive behavioural therapy arm , 374 in the attention control arm , and 298 in the usual school provision arm . At 12 months adjusted mean scores on the short mood and feelings question naire did not differ for cognitive behavioural therapy versus attention control ( −0.63 , 95 % confidence interval −1.85 to 0.58 , P=0.41 ) or for cognitive behavioural therapy versus usual school provision ( 0.97 , −0.20 to 2.15 , P=0.12 ) . Conclusion In adolescents with depressive symptoms , outcomes were similar for attention control , usual school provision , and cognitive behavioural therapy . Classroom based cognitive behavioural therapy programmes may result in increased self awareness and reporting of depressive symptoms but should not be undertaken without further evaluation and research . Trial registration Current Controlled Trials IS RCT N19083628 OBJECTIVE The present study evaluated the impact of a national school programme of universal free healthy breakfast provision in Wales , UK . DESIGN A cluster r and omised controlled trial with repeated cross-sectional design and a 12-month follow-up . Primary outcomes were breakfast skipping , breakfast diet and episodic memory . Secondary outcomes were frequency of eating breakfast at home and at school , breakfast attitudes , rest-of-day diet and class behaviour . SETTING Primary schools in nine local education authority areas . SUBJECTS A total of 4350 students ( aged 9 - 11 years ) at baseline and 4472 at follow-up in 111 schools . RESULTS Students in intervention schools reported significantly higher numbers of healthy food items consumed at breakfast and more positive attitudes towards breakfast eating at 12 months . Parents in intervention schools reported significantly higher rates of consumption of breakfast at school and correspondingly lower rates of breakfast consumption at home . No other significant differences were found . CONCLUSIONS The intervention did not reduce breakfast skipping ; rather , pupils substituted breakfast at home for breakfast at school . However , there were improvements in children 's nutritional intake at breakfast time , if not the rest of the day , and more positive attitudes to breakfast , which may have implication s for life-course dietary behaviours . There was no impact on episodic memory or classroom behaviour , which may require targeting breakfast skippers OBJECTIVE To explore whether the effects on dietary behaviours of a computer-tailored intervention aim ed to prevent excessive weight gain among adolescents , FATaintPHAT , were moderated by sociodemographic , cognitive and home environmental factors . DESIGN A two-group cluster r and omized trial . Potential moderation of the outcome measures ( consumption of sugar-sweetened beverages , snacks , fruits and vegetables ) was studied by gender , education level , ethnicity , awareness of risk behaviour , intention and home availability . SETTING Twenty schools in the Netherl and s. SUBJECTS Students ( n 883 ) aged 12 - 13 years . RESULTS Of the twenty-four interactions tested , only three were significant . The intervention effect on sugar-sweetened beverages was moderated by level of education ( P = 0·009 ) ; intervention effects were found only among academic preparatory students . The intervention effects on fruit and vegetable intake were moderated by awareness of fruit intake ( P < 0·001 ) and home availability of vegetables ( P = 0·007 ) ; an effect on fruit intake was found only among students who were aware of their low fruit intake at baseline and an effect on vegetable consumption was found only among students who reported that vegetables were always available at their home . CONCLUSIONS The effects of the intervention generally did not differ between sociodemographic subgroups . The moderation by home availability illustrates that the environment may influence the effects of educational interventions Background To promote well-being and health behaviors among adolescents , 2 interventions were implemented at 12 secondary schools . Adolescents in the E-health4Uth group received Web-based tailored messages focused on their health behaviors and well-being . Adolescents in the E-health4Uth and consultation group received the same tailored messages , but were subsequently referred to a school nurse for a consultation if they were at risk of mental health problems . Objective This study evaluated the effect of E-health4Uth and E-health4Uth and consultation on well-being ( ie , mental health status and health-related quality of life ) and health behaviors ( ie , alcohol and drug use , smoking , safe sex ) . Methods A cluster r and omized controlled trial was conducted among third- and fourth-year secondary school students ( mean age 15.9 , SD 0.69 ) . School classes ( clusters ) were r and omly assigned to ( 1 ) E-health4Uth group , ( 2 ) E-health4Uth and consultation group , or ( 3 ) control group ( ie , care as usual ) . Adolescents completed a question naire at baseline and at 4-month follow-up assessing alcohol consumption , smoking , drug use , condom use , mental health via the Strengths and Difficulties Question naire ( SDQ ) and the Youth Self Report ( YSR ; only measured at follow-up ) , and health-related quality of life . Multilevel logistic , ordinal , and linear regression analyses were used to reveal differences in health behavior and well-being between the intervention groups and the control group at follow-up . Subsequently , it was explored whether demographics moderated the effects . Results Data from 1256 adolescents were analyzed . Compared to the control intervention , the E-health4Uth intervention , as a st and alone intervention , showed minor positive results in health-related quality of life ( B=2.79 , 95 % CI 0.72 - 4.87 ) and condom use during intercourse among adolescents of Dutch ethnicity ( OR 3.59 , 95 % CI 1.71 - 7.55 ) not replicated in the E-health4Uth and consultation group . The E-health4Uth and consultation intervention showed minor positive results in the mental health status of adolescents ( SDQ : B=−0.60 , 95 % CI −1.17 to −0.04 ) , but a negative effect on drug use among boys ( OR 0.36 , 95 % CI 0.13 - 0.96 ) . In the subgroup of adolescents who were at risk of mental health problems at baseline ( and referred for a consultation with the nurse ) , the E-health4Uth and consultation group showed minor to moderate positive results in mental health status ( SDQ : B=−1.79 , 95 % CI −3.35 to −0.22 ; YSR : B=−9.11 , 95 % CI −17.52 to −0.71 ) and health-related quality of life ( B=7.81 , 95 % CI 2.41 - 13.21 ) at follow-up compared to adolescents in the control group who were at risk of mental health problems at baseline . Conclusions Findings from this study support the use of the E-health4Uth and consultation intervention in promoting the well-being of adolescents at risk of mental health problems . Future research is needed to further evaluate the effects of the consultation as a st and alone intervention , and the dual approach of further tailored eHealth messages and a consultation . Trial Registration Nederl and s Trial Register : NTR 3596 ; http://www.trialregister.nl/trialreg/admin/ rct view.asp?TC=3596 ( Archived by WebCite at http://www.webcitation.org/6PmgrPOuv ) Background School-based interventions that target prevention of overweight and obesity in children have been tested with mixed results . Thus , successful interventions are still called for . The aim of the present study was to investigate effects of a multicomponent school-based intervention programme targeting physical activity , sedentary and dietary behaviours on anthropometric outcomes . Methods A 20-month intervention was evaluated in a cluster r and omised , controlled study of 1324 11-year-olds . Outcome variables were body mass index ( BMI ) , BMI -for-age z-score ( BMI z ) , waist circumference ( WC ) , waist-to-height ratio ( WTHR ) and weight status ( International Obesity Task Force 's cut-offs ) . Weight , height and WC were measured objective ly ; pubertal status was self-reported and parental education was self-reported by the parents . Intervention effects were determined by one-way analysis of covariance and logistic regression , after checking for clustering effects of school , and moderating effects of gender , pubertal status and parental education . Results Beneficial effects were found for BMI ( p=0.02 ) and BMI z ( p=0.003 ) in girls , but not in boys . While a beneficial effect was found for BMI ( p=0.03 ) in participants of parents reporting a high level of education , a negative effect was found for WTHR in participants with parents reporting a low level of education ( p=0.003 ) . There were no intervention effects for WC and weight status . Conclusions A multicomponent 20-month school-based intervention had a beneficial effect on BMI and BMI z in adolescent girls , but not in boys . Furthermore , children of higher educated parents seemed to benefit more from the intervention , and this needs attention in future interventions to avoid further increase in social inequalities in overweight and obesity Objective : To assess the efficacy of a school-based intervention programme to reduce the prevalence of overweight in 6 to 10-year-old children . Design : Cluster-r and omized , controlled study .Subjects : A total of 3135 boys and girls in grade s 1–4 were included in the study . Methods : Ten schools were selected in Stockholm county area and r and omized to intervention ( n=5 ) and control ( n=5 ) schools . Low-fat dairy products and whole-grain bread were promoted and all sweets and sweetened drinks were eliminated in intervention schools . Physical activity ( PA ) was aim ed to increase by 30 min day−1 during school time and sedentary behaviour restricted during after school care time . PA was measured by accelerometry . Eating habits at home were assessed by parental report . Eating disorders were evaluated by self-report . Results : The prevalence of overweight and obesity decreased by 3.2 % ( from 20.3 to 17.1 ) in intervention schools compared with an increase of 2.8 % ( from 16.1 to 18.9 ) in control schools ( P<0.05 ) . The results showed no difference between intervention and controls , after cluster adjustment , in the longitudinal analysis of BMI sds changes . However , a larger proportion of the children who were initially overweight reached normal weight in the intervention group ( 14 % ) compared with the control group ( 7.5 % ) , P=0.017 . PA did not differ between intervention and control schools after cluster adjustment . Eating habits at home were found to be healthier among families with children in intervention schools at the end of the intervention . There was no difference between children in intervention and control schools in self-reported eating disorders . Conclusions : A school-based intervention can reduce the prevalence of overweight and obesity in 6 to 10-year-old children and may affect eating hab Output:	Effects of multi-level interventions on ine quality were inconsistent . Conclusions Universal school-based interventions may narrow , widen or have no effect on ine quality .
MS212055	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: STUDY OBJECTIVE To investigate the relationships between cytochrome P450 ( CYP ) 2D6 genotype , antipsychotic drug exposure , abnormal movements and tardive dyskinesia , and cigarette smoking . DESIGN Prospect i ve , longitudinal study . SETTING University mental health research center . PATIENTS Thirty-seven patients with schizophrenia . INTERVENTION Patients were genotyped for CYP2D6 * 1 , * 3 , and * 4 alleles , and data were collected on their psychiatric symptoms , cigarette smoking status , and antipsychotic drug exposure . Abnormal movements were measured using the Abnormal Involuntary Movement Scale ( AIMS ) . Presence of tardive dyskinesia was also evaluated . MEASUREMENTS AND MAIN RESULTS A linear regression model used the AIMS scores as the dependent variable , and genotype , sex , smoking status , and antipsychotic drug exposure as independent variables . Antipsychotic drug exposure , genotype , and cigarette smoking interaction was significant ( p<0.0212 ) for patients with the CYP2D6 * 1/3 , 4 genotype . Seventy-eight percent of smokers with the CYP2D6 * 1/3 , 4 genotype had tardive dyskinesia compared with 20 - 33 % of patients in other groups . CONCLUSION Patients with a CYP2D6 * 3 or * 4 allele may shunt antipsychotic metabolism through other pathways that are induced by cigarette smoke . This induction may result in formation of neurotoxic metabolites , leading to increased AIMS scores and a higher frequency of tardive dyskinesia compared with patients without these alleles Cytochrome P450 ( CYP ) genotyping can be used to prospect ively identify individuals at risk for adverse drug reactions or therapeutic failure due to altered drug metabolism . Based on the specific CYP(s ) affected , individuals may require less or more of a particular drug than people with unaffected CYP-mediated metabolism , or may be best managed by avoiding certain drugs entirely . Here we evaluated the Tag-It ™ CYP mutation detection reagents ( Tm Bioscience Corp. ) . As these reagents , based on a universal bead array , detect more than 20 clinical ly significant variants common to different ancestries , it was important to consider DNA from genetically diverse population s. Thus , we also report CYP2D6 , CYP2C9 and CYP2C19 genotypes for DNA available through the Coriell Institute for Medical Research ( NJ , USA ) . These sample s represent individuals from Caucasian , Japanese , Chinese , Southeast Asian , African – American and Middle Eastern ancestry , and provide an excellent re source for evaluating and validating CYP genotyping methods . Using these sample s , the Tag-It mutation detections assays reliably provided genotypes for CYP2D6 , CYP2C9 and CYP2C19 . The CYP2C9 and CYP2C19 assays were particularly robust and were easily implemented in our clinical laboratory . The CYP2D6 assay was somewhat less robust and could be improved by associating the 2850C > T variant with a specific allele , as well as by discriminating the allele affected when gene duplication is detected Abstract . Objective : In order to evaluate whether poor metabolizers ( PM ) of debrisoquine are overrepresented among patients with acute dystonic reactions and chronic movement disorders associated with the administration of antipsychotic drugs , the CYP2D6 genotype was determined in schizophrenic patients . Methods : Allele status for CYP2D6 * 3 , CYP2D6 * 4 , CYP2D6 * 5 , and CYP2D6 * 6 as well as gene duplication was determined by allele-specific PCR , long-PCR and restriction fragment length polymorphism analysis ( RFLP ) in 119 schizophrenic patients ( 99 males and 20 females ) . All subjects were treated with antipsychotics metabolized , at least partially , by this isozyme . Sixty-three of the patients ( 52.9 % ) had a history of extrapyramidal side effects ( EPS ) , while 56 ( 47.1 % ) had not experienced such problems ( controls ) . Results : Sixty-five patients ( 54.6 % ) were homozygous for a functional CYP2D6 * 1 allele , 44 ( 37.0 % ) were heterozygous for detrimental alleles , and 4 ( 3.4 % ) , who carried two detrimental alleles , were classified as PM . In six patients ( 5.0 % ) duplication of a functional CYP2D6 gene was found , and they were consequently classified as ultrarapid metabolizers ( UM ) . Homo- and heterozygous extensive metabolizers ( EM ) as well as UM were equally distributed between patients with and without EPS , whereas all the PM had a history of EPS . No significant differences in allele frequencies between the two groups were found . Conclusion : Although the results can not be considered conclusive due to the small number of PM patients in our study , the PM genotype may be a predisposing factor for antipsychotic-induced EPS . Knowledge of the CYP2D6 genotype , before starting antipsychotic therapy , might be useful in identifying subjects at risk of developing EPS Abstract Introduction Assessment of the relation between oral risperidone dose , serum drug levels and clinical response may provide important information for rational treatment decisions . Inter – individual differences in the liver cytochrome P450 system , especially in the CYP2D6 subsystem , which account for a significant portion of risperidone metabolism , may also influence plasma drug levels and alter clinical response parameters . We thus prospect ively investigated risperidone serum concentrations in relation to clinical efficacy and side – effects and genotyped major CYP2D6 polymorphisms to determine their effect upon these parameters . Methods Neuroleptic monotherapy with risperidone was administered to schizophrenia patients in a 6–week open dose clinical trial . Weekly assessment s including CGI and PANSS ratings to assess psychopathology ; SAS to assess medication side effects ; and blood draws to quantify steady state plasma levels of risperidone and 9–OH – risperidone were carried out . In addition , major CYP2D6 polymorphisms including alleles * 4 , * 6 and * 14 were genotyped . Results Eighty – two patients were recruited . Mean oral dose of risperidone was 4.3 ± 0.9 mg . Mean plasma level of both risperidone and 9–OH – risperidone together ( “ active moiety ” ) was 41.6 ± 26.6 ng/ml . Significant improvements in PANSS scales and the various subscales ensued . There was a positive linear correlation between active moiety plasma levels and dose ( r = 0.291 , p = 0.015 ) and between risperidone and 9–OH – risperidone levels ( r = 0.262 ; p = 0.016 ) . Nonresponders to pharmacotherapy ( PANSS – Improvement < 30 % ) showed significantly higher active moiety plasma levels ( 49.9 ± 30.7 ng/ml ) than responders ( 38.2 ± 17.0 ng/ml ; p = 0.045 ) without significantly higher oral doses ( p = 0.601 ) . Patients with longer illness duration ( ≥ 3 years ) had significantly higher plasma drug levels than those with a shorter course ( < 3 years ; p = 0.039 ) . Extrapyramidal side effects ( EPS ) and plasma levels were not correlated ( r = 0.028 ; p = 0.843 ) , but higher plasma levels at week 2 predicted an incidence for EPS ( p < 0.050 ) . Accordingly , patients initially receiving higher oral doses of risperidone were significantly more likely to respond with EPS in the trial course . Eight patients ( 9.8 % ) were heterozygous carriers of the CYP2D6 allele * 4 . CYP2D6 polymorphisms did not predict clinical response , but predicted a tendential increase in the plasma risperidone to 9–OH – risperidone ratio ( 0.5 ± 0.6 vs. 1.9 ± 1.8 ; p = 0.120 ) . Discussion The major finding was that responders to risperidone treatment had significantly lower blood levels of risperidone and 9–OH risperidone than patients who did not respond to the treatment despite administration of similar oral doses . The observed CYP2D6 polymorphisms did not contribute to altered clinical efficacy , but affected risperidone to 9–OH – risperidone ratios . Increased plasma levels of the active moiety in patients with longer illness may represent general aging effects . Conversely , the observed higher plasma levels in nonresponders may derive from unaccounted genetic metabolism abnormalities or Phase II metabolism disturbances . Patients initially receiving higher oral risperidone doses were more likely to respond with extrapyramidal side effects which reaffirms the need for careful titration . The high inter – individual variability in risperidone and 9–OH – risperidone metabolization and the relationship between clinical outcome and plasma levels warrants regular plasma level monitoring of both compounds to assess for the clinical ly relevant active moiety AIM Cytochrome P450 2C9 ( CYP2C9 ) is a polymorphic enzyme responsible for the metabolism of a large number of clinical ly important drugs . Individuals with mutant enzymes may risk serious side effects under routine therapy with certain drugs metabolized by CYP2C9 . In order to facilitate the detection of the known SNPs of CYP2C9 , an allele-specific oligonucleotide ( ASO ) based microarray was made . METHODS An oligonucleotide microarray was made to facilitate the SNP ( single nucleotide polymorphism ) screening and was applied for the detection of CYP2C9 polymorphism in 62 high blood pressure ( HBP ) patients who received Irbesartan for treatment . Part of the genotyping results was confirmed by direct sequencing . And the relation between CYP2C9 polymorphism and therapeutic outcome of Irbesartan was statistically analyzed . RESULTS Heterozygous alleles of CYP2C9 * 1/3 were found in 7 out of 62 subjects . No mutant alleles of CYP2C9 2 , * 4 and * 5 and no homozygous mutant alleles were detected . The 7 heterozygous CYP2C9 * 1/3 and 13 r and om wild type DNA sample s were subjected to direct sequencing with purified PCR products and same genotyping results were obtained with the 20 DNA sample s. There was no significant difference in the odds of effectiveness of Irbesartan between the wild type ( normal ) group and CYP2C9 1/3 ( mutant ) group ( P>0.05 ) . CONCLUSION The oligonucleotide microarray made in this study is a reliable assay for detecting the CYP2C9 known alleles and the heterozygous CYP2C9 1/*3 has no significant effects on the therapeutic outcome of Irbesartan Tardive dyskinesia ( TD ) is a movement disorder characterized by involuntary oro‐facial , limb , and truncal movements . As a genetic basis for inter‐individual variation is assumed , there have been a sizeable number of c and i date gene studies . All subjects met diagnostic criteria for schizophrenia and were r and omized to receive antipsychotic medications as participants in the Clinical Antipsychotic Trials of Intervention Effectiveness project ( CATIE ) . TD was assessed via the Abnormal Involuntary Movement Scale at regular intervals . Probable TD was defined as meeting Schooler – Kane criteria at any scheduled CATIE visit ( 207/710 subjects , 29.2 % ) . A total of 128 c and i date genes were studied in 710 subjects—2,580 SNPs in 118 c and i date genes selected from the literature ( e.g. , dopamine , serotonin , glutamate , and GABA pathways ) and composite genotypes for 10 drug‐metabolizing enzymes . No single marker or haplotype association reached statistical significance after adjustment for multiple comparisons . Thus , we found no support for either novel or prior associations from the literature . © 2009 Wiley‐Liss , BACKGROUND The relative effectiveness of second-generation ( atypical ) antipsychotic drugs as compared with that of older agents has been incompletely addressed , though newer agents are currently used far more commonly . We compared a first-generation antipsychotic , perphenazine , with several newer drugs in a double-blind study . METHODS A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and r and omly assigned to receive olanzapine ( 7.5 to 30 mg per day ) , perphenazine ( 8 to 32 mg per day ) , quetiapine ( 200 to 800 mg per day ) , or risperidone ( 1.5 to 6.0 mg per day ) for up to 18 months . Ziprasidone ( 40 to 160 mg per day ) was included after its approval by the Food and Drug Administration . The primary aim was to delineate differences in the overall effectiveness of these five treatments . RESULTS Overall , 74 percent of patients discontinued Output:	However , there was limited evidence of the role of CYP2D6 polymorphisms in antipsychotic efficacy , although there was an association between CYP2D6 genotype and extrapyramidal adverse effects .
MS212056	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: This study evaluated the relevance of the Lake Louise acute mountain sickness ( AMS ) scoring system in comparison with other AMS scoring systems . To achieve this objective nine subjects were su bmi tted to a 9-hr exposure to hypoxia in a hypobaric chamber ( altitude 4500 - 5500 m ) that led to the development of AMS . AMS was scored at the end of this exposure period both by question naires ( Hackett AMS question naire , Lake Louise AMS self-report question naire , Environmental Symptoms Question naire ESQ II and ESQ IV ) and by a clinical investigation following the Lake Louise AMS clinical and functional AMS assessment . The AMS scores were between 0 and 9 for the Hackett AMS score , 0 and 38 for the ESQ II AMS score , 0 and 13.7 for the ESQ IV AMS score , 0 and 10 for the Lake Louise AMS self-report , 0 and 2 for the Lake Louise AMS clinical assessment score , and between 0 and 2 for the Lake Louise functional score . All the AMS question naire scores were related to the clinical AMS assessment score ( p < 0.05 ) without significant differences between them . The Lake Louise AMS self-report score appeared highly correlated to other AMS scoring systems ( Hackett , ESQ II and ESQ IV ) ( p < 0.05 ) . Suggestions were proposed to improve the sensitivity and the specificity of the Lake Louise AMS scoring question naire but also the Lake Louise AMS clinical assessment . In conclusion , this study suggests the relevance of the Lake Louise AMS self-report question naire to assess and score AMS with simplicity and rapidity Abstract : A study was carried out to determine the effectiveness of low doses of acetazolamide in ameliorating the symptoms of altitude sickness . Subjects were placed in a low pressure chamber at either 14,000 ft . or 3,000 ft . for 24 hours . Before entering the chamber each subject took a total of 750 mg . of acetazolamide or a placebo . During their 24-hour stay , the subjects filled out a question naire design ed to evaluate their state of well-being . End-tidal PCO2 was measured , and electrodes were applied for monitoring respiratory pattern and EEG . Subjects were given a ranking of 1 ( worst ) to 4 ( best ) comparing individual clinical states . Sample s of arterial blood and cerebrospinal fluid were obtained and analyzed for pH , PO2 , PCO2 , CO2 , HCO3(- ) , and lactate . Twenty-four-hour urine volumes were analyzed for Na , K , and 17-hydroxycorticosteroids . Acetazolamide significantly lowered arterial and CSF HCO3(- ) , arterial and end-tidal PCO2 , and arterial pH. The mean arterial PO2 was higher in those receiving acetazolamide , but the increase was not significant ( P < .10 ) . Pretreatment with acetazolamide was of sufficient clinical benefit to allow its recommendation prior to altitude exposure . ( Author In this r and omized , double-blind placebo controlled trial our objectives were to determine if acetazolamide is capable of preventing high altitude pulmonary edema ( HAPE ) in trekkers traveling between 4250 m (Pheriche)\4350 m ( Dingboche ) and 5000 m ( Lobuje ) in Nepal ; to determine if acetazolamide decreases pulmonary artery systolic pressures ( PASP ) at high altitude ; and to determine if there is an association with PASP and signs and symptoms of HAPE . Participants received either acetazolamide 250 mg PO BID or placebo at Pheriche\Dingboche and were reassessed in Lobuje . The Lake Louise Consensus Criteria were used for the diagnosis of HAPE , and cardiac ultrasonography was used to measure the velocity of tricuspid regurgitation and estimate PASP . Complete measurements were performed on 339 of the 364 subjects ( 164 in the placebo group , 175 in the acetazolamide group ) . No cases of HAPE were observed in either study group nor were differences in the signs and symptoms of HAPE found between the two groups . Mean PASP values did not differ significantly between the acetazolamide and placebo groups ( 31.3 and 32.6 mmHg , respectively ) . An increasing number of signs and symptoms of HAPE was associated with elevated PASP ( p < 0.01 ) . The efficacy of acetazolamide against acute mountain sickness , however , was significant with a 21.9 % incidence in the placebo group compared to 10.2 % in the acetazolamide group ( p < 0.01 ) . Given the lack of cases of HAPE in either group , we can draw no conclusions about the efficacy of acetazolamide in preventing HAPE , but the absence of effect on PASP suggests that any effect may be minor possibly owing to partial acclimatization during the trek up to 4200 Self-rated moods were determined twice daily with the Clyde Mood Scale on 35 human subjects at 200 m ( baseline ) during a study concerned with evaluating the efficacy of staging plus acetazolamide ( treatment ) for the prevention of acute mountain sickness ( AMS ) . Mood states also were determined on all subjects at 4300 m ( Pikes Peak , Co ) and on 18 of these subjects at 1600 m ( staging site ) . Mood state changes were not observed at 1600 m , but four of the six mood factors were sensitive to the 4300 m altitude . At 4300 m , all subjects , treatment and control , rated themselves as less friendly and clear thinking and more sleepy and dizzy . At 4300 m , the treatment strategy result ed in an improved mood on the friendly , sleepy , and dizzy factors . Altitude-induced changes in clear thinking were not altered by the treatment strategy Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Acute mountain sickness ( A.M.S. ) and its severe complications , high-altitude pulmonary oedema ( H.A.P.O. ) and cerebral oedema ( C.O. ) , were studied in 278 unacclimatised hikers at 4243 m altitude at Pheriche in the Himalayas of Nepal . The overall incidence of A.M.S. was 53 % , the incidence being increased in the young and in those who flew to 2800 m , climbed fast , and spent fewer nights acclimatising en route . It was unrelated to sex , to previous altitude experience , to the load carried , and to recent respiratory infections . The severity of A.M.S. was inversely related to age ( independent of rate of ascent ) and the highest altitude attained , and was highly ocrrelated with speed of ascent . There were 7 cases of H.A.P.O. and 5 with the more intractable C.O. and , of these 12 , 11 had flown in , 9 had spent only one night at Pheriche , and none were on acetazolamide . 11 required evacuation . Acetazolamide , compared in a double-blind study with a placebo and also compared with no tablets at all , reduced both the incidence and the severity of A.M.S. in those who flew to 2800 m but not in those who hiked up to that altitude . Prevention consists in slow ascent , rapid recognition of warning signs , and prompt descent to avoid progression BACKGROUND Acute mountain sickness ( AMS ) commonly occurs when unacclimatized individuals ascend to altitudes above 2000 m. Acetazolamide and Ginkgo biloba have both been recommended for AMS prophylaxis ; however , there is conflicting evidence regarding the efficacy of Ginkgo biloba use . We performed a r and omized , placebo-controlled trial of acetazolamide vs Ginkgo biloba for AMS prophylaxis . METHODS We r and omized unacclimatized adults to receive acetazolamide , Ginkgo biloba , or placebo in double-blind fashion and took them to an elevation of 3800 m for 24 hours . We grade d AMS symptoms using the Lake Louise Acute Mountain Sickness Scoring System ( LLS ) and compared the incidence of AMS ( defined as LLS score > or =3 and headache ) . RESULTS Fifty-seven subjects completed the trial ( 20 received acetazolamide ; 17 , Ginkgo biloba , and 20 , placebo ) . The LLS scores were significantly different between groups ; the median score of the acetazolamide group was significantly lower than that of the placebo group ( P=.01 ; effect size , 2 ; and 95 % confidence interval [ CI ] , 0 to 3 ) , unlike that of the Ginkgo biloba group ( P=.89 ; effect size , 0 ; and 95 % CI , -2 to 2 ) . Acute mountain sickness occurred less frequently in the acetazolamide group than in the placebo group ( effect size , 30 % ; 95 % CI , 61 % to -15 % ) , and the frequency of occurrence was similar between the Ginkgo biloba group and the placebo group ( effect size , -5 % ; 95 % CI , -37 % to 28 % ) . CONCLUSIONS In this study , prophylactic acetazolamide therapy decreased the symptoms of AMS and trended toward reducing its incidence . We found no evidence of similar efficacy for Ginkgo biloba Previous attempts to detect global cerebral hemodynamic differences between those who develop headache , nausea , and fatigue following rapid exposure to hypoxia [ acute mountain sickness ( AMS ) ] and those who remain healthy have been inconclusive . In this study , we investigated the effects of two drugs known to reduce symptoms of AMS to determine if a common cerebral hemodynamic mechanism could explain the prophylactic effect within individuals . With the use of r and omized , placebo-controlled , double-blind , crossover design , 20 healthy volunteers were given oral acetazolamide ( 250 mg ) , dexamethasone ( 4 mg ) , or placebo every 8 h for 24 h prior to and during a 10-h exposure to a simulated altitude of 4,875 m in a hypobaric chamber , which included 2 h of exercise at 50 % of altitude-specific VO(2max ) . Cerebral hemodynamic parameters derived from ultrasound assessment s of dynamic cerebral autoregulation and vasomotor reactivity were recorded 15 h prior to and after 9 h of hypoxia . AMS symptoms were scored using the Lake Louise Question naire ( LLQ ) . It was found that both drugs prevented AMS in those who became ill on placebo ( ~70 % decrease in LLQ ) , yet a common cerebral hemodynamic mechanism was not identified . Compared with placebo , acetazolamide reduced middle cerebral artery blood flow velocity ( 11 % ) and improved dynamic cerebral autoregulation after 9 h of hypoxia , but these effects appeared independent of AMS . Dexamethasone had no measureable cerebral hemodynamic effects in hypoxia . In conclusion , global cerebral hemodynamic changes result ing from hypoxia may not explain the development of AMS During an expedition to the Himalayas , we studied the sleep and respiration of six climbers . Three ingested acetazolamide ( 500 mg ) daily throughout the climb and the other three ingested placebo . At high altitude ( 4,150 - 4,846 m ) , each subject ingested temazepam ( 10 mg ) for one night and placebo for another . Acetazolamide improved sleep above 2,750 m , but it is uncertain whether this was due to sedation or to improvements in arterial oxygen saturation . Sleep was markedly disturbed in all subjects above 4,000 m. Temazepam improved sleep , and in subjects taking acetazolamide , it reduced sleep-onset latencies and increased sleep efficiency close to that of sea level values . These observations suggest that the prophylactic use of acetazolamide is likely to improve sleep in climbers and that a low dose of a benzodiazepine such as temazepam ( 10 mg ) may be beneficial at high altitude . Studies are now needed to exclude any possibility of respiratory impairment at altitude before a firm recommendation can be made regarding the routine use of this hypnotic Abstract Objective To evaluate the efficacy of ginkgo biloba , acetazolamide , and their combination as prophylaxis against acute mountain sickness . Design Prospect i ve , double blind , r and omised , placebo controlled trial . Setting Approach to Mount Everest base camp in the Nepal Himalayas at 4280 m or 4358 m and study end point at 4928 m during October and November 2002 . Participants 614 healthy western trekkers ( 487 completed the trial ) assigned to receive ginkgo , acetazolamide , combined acetazolamide and ginkgo , or placebo , initially taking at least three or four doses before continued ascent . Main outcome measures Incidence measured by Lake Louise acute mountain sickness score ≥ 3 with headache and one other symptom . Secondary outcome measures included blood oxygen content , severity of syndrome ( Lake Louise scores ≥ 5 ) , incidence of headache , and severity of headache . Results Ginkgo was not significantly different from placebo for any outcome ; however participants in the acetazolamide group showed significant levels of protection . The inc Output:	RESULTS Acetazolamide prophylaxis was associated with a 48 % relative-risk reduction compared to placebo . There was no evidence of an association between efficacy and dose of acetazolamide . Adverse effects were often not systematic ally reported but appeared to be common but generally mild . Acetazolamide is effective prophylaxis for the prevention of symptoms of AMS in those going to high altitude . A dose of 250 mg/day has similar efficacy to higher doses and may have a favorable side-effect profile
MS212057	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: In this double-blind , parallel-group , multicenter study , 169 patients with symptoms of maxillary sinusitis but without radiographically confirmed empyema ( pus ) were r and omly assigned to receive either 500 mg azithromycin once daily for 3 days ( 87 patients ) or placebo daily for 3 days ( 82 patients ) . Nasal secretion , maxillary tenderness and pain , nasal obstruction , general malaise , and hyposmia were assessed at the start of the study and on days 4 , 11 , and 25 of treatment . After 11 days 58 % of the patients in the azithromycin group were cured versus 31 % in the placebo group ; after 25 days the cure rate was 79 % versus 67 % , respectively . When both cure and improvement were considered , the corresponding figures after day 25 were 90 % and 88 % , respectively . Adverse events , predominantly gastrointestinal , occurred in 24 ( 27 % ) of the azithromycin-treated patients and in 15 ( 18 % ) of those treated with placebo , but the difference was not statistically significant . There was a difference in efficacy in favor of azithromycin in the treatment of rhinitis with symptoms of maxillary sinusitis but without radiological signs of empyema ( pus ) . Antibiotics should only be used to alleviate symptoms in patients with moderate to severe symptoms , as the results after 25 days for both improvement and cure are equal . In the treatment of acute rhinitis with symptoms and signs of maxillary sinusitis but without empyema , treatment with azithromycin seems to result in a better cure rate after 10–12 days when compared with placebo OBJECTIVE To compare the efficacy of amoxicillin vs placebo in patients with an acute upper respiratory tract infection and purulent rhinorrhea . STUDY DESIGN Double-blind r and omized placebo-controlled trial . POPULATION The 416 patients included from 69 family practice s were 12 years or older , presenting with acute upper respiratory complaints , and having a history of purulent rhinorrhea and no signs of complications of sinusitis . OUTCOMES MEASURED Therapy success ( disappearance of symptoms that most greatly affected the patient 's health ) at day 10 and duration of general illness , pain , and purulent rhinorrhea . RESULTS Therapy was successful in 35 % of patients with amoxicillin and in 29 % of patients with placebo ( relative risk [ RR ] 1.14 , 95 % confidence interval [ CI ] , 0.92 - 1.42 ) . There was no effect on duration of general illness or pain . Duration of purulent rhinorrhea was shortened by amoxicillin ( 9 days vs 14 for clearing of purulent rhinorrhea in 75 % of patients ; P = .007 ) . Diarrhea was more frequent with amoxicillin ( 29 % vs 19 % , RR 1.28 , 95 % CI , 1.05 - 1.57 ) . No complications were reported . One patient ( 0.5 % ) receiving amoxicillin and 7 ( 3.4 % ) receiving placebo discontinued trial therapy because of exacerbation of symptoms ( RR 0.25 , 95 % CI 0.04 - 1.56 , P = .07 ) . All 8 patients recovered with antibiotic therapy . CONCLUSIONS Amoxicillin has a beneficial effect on purulent rhinorrhea caused by an acute infection of the nose or sinuses but not on general recovery . The practical implication is that all such patients , whatever the suspected diagnosis , can be safely treated with symptomatic therapy and instructed to return if symptoms worsen BACKGROUND Sinusitis is the fifth most common reason for patients to visit primary care physicians , yet clinical outcomes relevant to patients are seldom studied . OBJECTIVE To determine whether patients with purulent rhinitis , " sinusitis-type symptoms , " improved with antibiotics . Second , to examine a clinical prediction rule to provide preliminary validation data . METHODS Prospect i ve clinical trial , with double-blinded placebo controlled r and omization . The setting was a suburb of Washington , DC , from Oct 1 , 2001 , to March 31 , 2003 . All participants were 18 years or older , presenting to a family practice clinic with a complaint of sinusitis and with pus in the nasal cavity , facial pressure , or nasal discharge lasting longer than 7 days . The main outcome measures were resolution of symptoms within a 14-day follow-up period and the time to improvement ( days ) . RESULTS After exclusion criteria , 135 patients were r and omized to either placebo ( n=68 ) or amoxicillin ( n=67 ) for 10 days . Intention-to-treat analyses showed that 32 ( 48 % ) of the amoxicillin group vs 25 ( 37 % ) of the placebo group ( P=.26 ) showed complete improvement by the end of the 2-week follow-up period ( relative risk=1.3 ; 95 % confidence interval [ CI ] , 0.87 - 1.94 ] ) . Although the rates of improvement were not statistically significantly different at the end of 2 weeks , the amoxicillin group improved significantly earlier , in the course of treatment , a median of 8 vs 12 days , than did the placebo group ( P=.039 ) . CONCLUSION For most patients with sinusitis-type complaints , no improvement was seen with anti-biotics over placebo . For those who did improve , data suggested there is a subgroup of patients who may benefit from antibiotics Summary In 50 adults with bacterial sinusitis , cyclacillin ( 1500 mg . per day for 7 days ) proved significantly more effective than placebo in eliminating the signs and symptoms and in eradicating the causative microorganisms , ( Staphylococcus aureus , Proteus mirabilis , and Staph , epidermidis were most frequently isolated in this series ) . Sixty percent of the cultures in the cyclacillin series were sterilized , compared with only 10 % in the placebo series . Globally , 93 % of the cyclacillin-treated patients and only 55 % of the placebo-treated patients were considered improved . Of the P. mirabilis strains encountered , 72 % were eradicated by cyclacillin ( only 40 % by placebo ) despite the relatively high cyclacillin M.I.C.s for this microorganism ( 50 to 100 μg/ml . ) . Cyclacillin was much more effective in treating human sinusitis than would have been anticipated from the M.I.C.s alone Sc and J Prim Health Care 2003;21:00 - 00 . ISSN 0281 - 34323 Objectives r - r To compare antibiotics and placebo in patients with clinical ly diagnosed acute maxillary sinusitis ( AMS ) . To study whether sinus ultrasound examination would help to detect those patients who benefit from antibiotic therapy . Design r - r A double-blind , r and omised , placebo-controlled multicentre trial . Setting r - r Nine primary care sites in Finl and . Subjects r - r 150 adult patients ( mean age 39.7 years ) with a clinical diagnosis of sinusitis . Intervention r - r Antibiotics ( amoxicillin 750 mg 2 2 , doxycycline 100 mg 2 2 or penicillin V 1500 mg 2 2 ) or placebo twice daily for 7 days ; all patients were examined with sinus ultrasound after r and omisation . Main outcome measure r - r Clinical success ( patients ' report of recovery ) in telephone interview at 2 weeks . Results r - r A total of 146 patients completed the 2-week follow-up . Patients receiving antibiotics achieved a slightly higher rate of clinical success than patients receiving placebo ( 80 % vs 66 % ; p=0.068 ) . Conclusions r - r Antibiotics hasten symptom relief in AMS . Yet many patients recover in 2 weeks without antimicrobial treatment . Only half of patients with a clinical diagnosis of AMS have sinusitis in ultrasound examination Abstract Objective : To compare the effectiveness of penicillin V and amoxycillin with placebo in treatment of adult patients with acute sinusitis . Design : R and omised , double blind , placebo controlled trial . Setting : Norwegian general practice . Subjects : 130 adult patients with a clinical diagnosis of acute sinusitis confirmed by computed tomography . Main outcome measures : Subjective status after three and 10 days of treatment , difference in clinical severity score between day 0 and day 10 as evaluated by the general practitioner , difference in score from computed tomography on day 0 and day 10 , and duration of sinusitis . Results : Amoxycillin and penicillin V led to significantly faster and better recovery than placebo . By day 10 , 71 patients receiving antibiotic treatment ( 86 % ) considered themselves to be recovered or much better compared with 25 ( 57 % ) receiving placebo . The mean ( 95 % confidence interval ) reductions in clinical severity scores by day 10 were 5.4 ( 5.0 to 5.8 ) for penicillin V , 5.5 ( 4.9 to 6.0 ) for amoxycillin , and 3.4 ( 2.8 to 4.0 ) for placebo . For the antibiotic groups combined the number of patients with the greatest degree of improvement on computed tomography ( scale 0 - 16)—that is , score 5 - 16 on day 10—was 31/83 ( 37 % ) compared with 10/44 ( 23 % ) receiving placebo . The median duration of the sinusitis was nine days in the amoxycillin group , 11 days in the penicillin V group , and 17 days in the placebo group . Conclusion : Penicillin V and amoxycillin are significantly more effective than placebo in the treatment of acute sinusitis . Key messages The median duration of sinusitis with different treatment was nine days for amoxycillin , 11 days for penicillin V , and 17 days for placebo More than half of the patients receiving antibiotic treatment reported side effects but few gave severe discomfort Half of the patients receiving placebo tablets felt restored or much better after 10 BACKGROUND Acute rhinosinusitis is one of the most common reasons for prescribing antibiotics in primary care . However , it is not clear whether antibiotics improve the outcome for patients with clinical ly diagnosed acute rhinosinusitis . We evaluated the effect of a combination product of amoxicillin-potassium clavulanate on adults with acute rhinosinusitis that was clinical ly diagnosed in a general practice setting . METHODS We conducted a r and omized , placebo-controlled , double-blind trial with 252 adults recruited at 24 general practice s and 2 outpatient clinics . Each patient had a history of purulent nasal discharge and maxillary or frontal pain for at least 48 hours . Patients were given amoxicillin , 875 mg , and clavulanic acid , 125 mg , or placebo twice daily for 6 days . Main outcome measures were time to cure ( primary outcome ) , number of days during which rhinosinusitis restricted activities at home or work , and frequency of adverse effects ( secondary outcomes ) . RESULTS The adjusted hazard ratio for the effect of amoxicillin-clavulanate was 0.99 ( 95 % confidence interval [ CI ] , 0.68 - 1.45 ) on time to cure and 1.28 ( 95 % CI , 0.80 - 2.05 ) in the prespecified subgroup of patients with a positive rhinoscopy result . At 7 days the mean difference between amoxicillin-clavulanate and placebo was -0.29 ( 95 % CI , -0.93 to 0.34 ) in the number of days with restrictions due to rhinosinusitis and -0.60 ( 95 % CI , -1.41 to 0.21 ) in patients with a positive rhinoscopy result . At 7 days patients who took amoxicillin-clavulanate were more likely to have diarrhea ( odds ratio , 3.89 ; 95 % CI , 2.09 - 7.25 ) . CONCLUSIONS Adult patients in general practice with clinical ly diagnosed acute rhinosinusitis experience no advantage with antibiotic treatment with amoxicillin-clavulanate and are more likely to experience adverse effects We compared the efficacy of penicillin V and amoxycillin treatment with placebo in 70 adult patients from Norwegian family practice with a clinical diagnosis of acute sinusitis and mucosal thickening on CT , but without fluid level or total opacification . The study was r and omized and double-blind . Three different outcomes were evaluated ; subjective status after 10 days of treatment , difference in clinical score between day 0 and day 10 , and duration of the illness episode . Amoxycillin and penicillin V gave no better response to treatment than placebo , evaluated by all three outcome measures . The median duration of the sinusitis episode was 10 days in the amoxycillin- and placebo groups and 13 days in the penicillin-V group . In patients with a clinical diagnosis of acute sinusitis , fluid level and total opacification on CT are good criteria to differentiate between groups of patients that need or do not need antibiotic treatment Abstract The aim of the present study was to assess the hypothesis Output:	Compared to placebo , antibiotic treatment relieves symptoms in a significantly higher proportion of patients within the first days of treatment . Reporting an overall average treatment efficacy may underestimate treatment benefits in patients with a self-limiting illness
MS212058	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Publication bias , sometimes known as the " file-drawer problem " or " funnel-plot asymmetry , " is common in empirical research . The authors review the implication s of publication bias for quantitative research synthesis ( meta- analysis ) and describe existing techniques for detecting and correcting it . A new approach is proposed that is suitable for application to meta-analytic data sets that are too small for the application of existing methods . The model estimates parameters relevant to fixed-effects , mixed-effects or r and om-effects meta- analysis contingent on a hypothetical pattern of bias that is fixed independently of the data . The authors illustrate this approach for sensitivity analysis using 3 data sets adapted from a commonly cited reference work on research synthesis ( H. M. Cooper & L. V. Hedges , 1994 ) Theoretical frameworks highlight the importance of threat-related information-processing biases for underst and ing the emergence of anxiety in childhood . The psychometric properties of several tasks measuring these biases and their associations with anxiety were examined in an unselected sample of 9-year-old children ( N=155 ) . In each task , threat bias was assessed using bias scores reflecting task performance on threat versus non-threat conditions . Reliability was assessed using split-half and test-retest correlations of mean reaction times ( RTs ) , accuracy and bias indices . Convergence between measures was also examined . Mean RTs showed substantial split-half and test-retest correlations . Bias score reliability coefficients were near zero and non-significant , suggesting poor reliability in children of this age . Additionally , associations between bias scores and anxiety were weak and inconsistent and performance between tasks showed little convergence . Bias scores from RT based paradigms in the current study lacked adequate psychometric properties for measuring individual differences in anxiety-related information-processing in children Social fears and worries in children are common and impairing . Yet , questions have been raised over the efficacy , suitability and accessibility of current frontline treatments . Here , we present data on the effectiveness of a novel parent-administered Cognitive Bias Modification of Interpretations ( CBM-I ) training tool . CBM-I capitalises on findings demonstrating an association between anxiety symptoms and biased interpretations , the tendency to interpret ambiguous situations negatively . Through CBM-I training , participants are exposed to benign resolutions , and reinforced for selecting these . In adults and adolescents , CBM-I training is effective at reducing symptoms and mood reactivity . In the present study , we developed a novel , child-appropriate form of CBM-I training , by presenting training material s within bedtime stories , read by a parent to the child across three consecutive evenings . Compared to a test-retest control group ( n = 17 ) , children receiving CBM-I ( n = 19 ) reported greater endorsement of benign interpretations of ambiguous situations post-training ( compared to pre-training ) . These participants ( but not the test-retest control group ) also showed a significant reduction in social anxiety symptoms . Pending replication and extensions to a clinical sample , these data may implicate a cost-effective , mechanism-driven and developmentally-appropriate re source for targeting social anxiety problems in children According to cognitive theories of anxiety , anxious adults interpret ambiguous situations in a negative way : They overestimate danger and underestimate their abilities to cope with danger . The present study investigated whether children with social phobia , separation anxiety disorder , and generalized anxiety disorder have such a bias , compared to a clinical and a normal control group . Children were exposed to stories in which ambiguous situations were described , and asked to give their interpretations , using open and closed responses . Results showed that anxious children reported more negative cognitions than control children . However , anxious children did not overestimate danger on the free responses , but they did judge the situations as more dangerous on the closed responses . Anxious children had lower estimations of their own competency to cope with danger than the control groups on both open and closed responses . The results indicate that children with anxiety disorders have dysfunctional cognitions about ambiguous situations OBJECTIVE This study evaluated follow-up outcomes associated with cognitive behavioral therapy ( CBT ) for childhood anxiety by comparing successfully and unsuccessfully treated participants 6.72 to 19.17 years after treatment . METHOD Participants were a sample of 66 youths ( ages 7 - 14 years at time of treatment , ages 18 - 32 years at present follow-up ) who had been diagnosed with an anxiety disorder and r and omized to treatment in a r and omized clinical trial on average 16.24 ( SD = 3.56 , range = 6.72 - 19.17 ) years prior . The present follow-up included self-report measures and a diagnostic interview to assess anxiety , depression , and substance misuse . RESULTS Compared with those who responded successfully to CBT for an anxiety disorder in childhood , those who were less responsive had higher rates of panic disorder , alcohol dependence , and drug abuse in adulthood . Relative to a normative comparison group , those who were less responsive to CBT in childhood had higher rates of several anxiety disorders and substance misuse problems in adulthood . Participants remained at particularly increased risk , relative to the normative group , for generalized anxiety disorder and nicotine dependence regardless of initial treatment outcome . CONCLUSIONS The present study is the first to assess the long-term follow-up effects of CBT treatment for an anxiety disorder in youth on anxiety , depression , and substance abuse through the period of young adulthood when these disorders are often seen . Results support the presence of important long-term benefits of successful early CBT for anxiety Many anxiety disorders begin in adolescence . Early interventions that target adolescent anxiety may prevent later disabling consequences . Previous studies show that cognitive bias modification training can generate positive interpretative styles of ambiguous information in adolescents but effects on anxious mood reduction are less clear . Adult studies suggest more consistent training effects on mood when assessed in response to a psychological challenge . Here , we assess whether positive training reduces adolescent anxious responses to a laboratory stressor . A total of 40 adolescents were r and omly assigned to positive or negative computerised training . During training , ambiguous scenarios were resolved positively or negatively . After training , adolescents completed a test of interpretation bias and a difficult mental arithmetic task while believing that they were being videotaped for teaching purpose s. First , positively-trained adolescents endorsed more positive and fewer negative interpretations of new ambiguous situations than negatively-trained adolescents . Second , positively-trained adolescents also showed attenuated anxiety levels after but not before the challenge . Induced positive interpretations via computerised cognitive training may modify anxious responsivity . Although there are some caveats to these data , in general they justify extensions of computerised training to adolescents with clinical anxiety , to reduce anxious responsivity Social functioning was assessed using the Child Behavior Checklist and Teacher Report Form for children with anxiety disorders who participated in a r and omized clinical trial ( N = 161 , aged 7–14 ) . Significant relationships were found between severity of children ’s principal anxiety disorder and most measures of social functioning , such that poorer social functioning was associated with more severe anxiety . Among youth who received cognitive-behavioral therapy ( n = 111 ) , significant associations were found between parent-reported social competence and both absence of principal anxiety disorder and lower anxiety severity at posttreatment and 1-year follow-up , controlling for the severity of the child ’s principal anxiety disorder at pretreatment . Findings support a relationship between anxiety severity and social difficulties , and suggest the importance of social competence for a favorable treatment response Output:	Two variables significantly moderated this effect . Specifically , the association increased in strength with increasing age and when the content of ambiguous scenarios matched the anxiety subtype under investigation . Results extend findings from adult literature by demonstrating an association in children and adolescents with evidence for content specificity in the association . Age effects imply a role for development .
MS212059	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: All 68,308 inhabitants of Göteborg born between 1918 and 1931 were r and omly divided into a test and a control group . The subjects in the test group were invited to perform Hemoccult II fecal occult blood testing on 3 days and to repeat the test after 16 to 24 months . In the prevalence screening 21,347 ( 63 % ) performed the test , and in the rescreening 19,991 ( 60 % ) . Investigation of the 942 ( 4.4 % ) with positive tests in the prevalence screening showed 47 cancers and 129 subjects with adenomas > or = 1.0 cm . In the rescreening 5.1 % had a positive test , and 34 cancers and 122 subjects with adenomas ( > or = 1.0 cm ) were found among those . Cancer had also been diagnosed in 19 subjects in the interval between the two screening occasions and in 15 subjects among the non-responders . Forty-four cancers had been diagnosed in the control group during the same period . Cancers detected by screening were at a less advanced stage than in the control group . It is too early to show any effect of screening on mortality from colorectal cancer Purpose Fecal immunochemical tests ( FITs ) have been developed to address analytical problems inherent in the older guaiac-based fecal occult blood tests ( g-FOBTs ) . Our aim was to compare the performance characteristics of one g-FOBT ( Hemoccult II ) and two FITs ( the Hemoccult ICT and MagStream HemSp ) relative to colonoscopy for the detection of colorectal cancer and significant precursor lesions . We also examined whether a 1-day collection strategy would negatively impact test diagnostic performance . Methods We used a prospect i ve observational cohort design in a Canadian population eligible for screening . All participants received colonoscopy after performing the occult blood tests . Results One thous and seventy-five individuals were enrolled ( mean age 56.3 years , 53.8 % females ) . Using colonoscopy as the gold st and ard , the sensitivity for screen-relevant neoplasm was determined for Hemoccult II ( 7.2 , 95 % CI : 1.1–13.4 ) , Hemoccult ICT ( 23.2 % : 13.2–33.1 ) , and MagStream HemSp using 67 μg/gram stool as the cut-off ( 23.2 % : 13.2–33.1 ) . The Magstream HemSp , using a cut-off threshold of 30 μg/gram stool , had the lowest specificity at 87.6 % ( 85.4–89.6 ) , while the Hemoccult II had the highest at 98.8 % ( 98.1–99.5 ) . Single-day stool testing reduced the false-positive rates of all tests without significantly reducing the sensitivity . Conclusion We found that FITs have a significantly increased sensitivity but reduced specificity for screen-relevant neoplasm compared to g-FOBT using colonoscopy as the gold st and ard . Optimal threshold levels for hemoglobin detection depend on the desired trade off between sensitivity and false-positive rate . Single-day testing with an FIT may be an option to enhance population compliance with screening BACKGROUND & AIMS Fecal DNA testing has shown greater sensitivity than guaiac-based occult blood tests for noninvasive colorectal cancer ( CRC ) screening . The prototype assay ( version 1 ) , which analyzed 22 gene mutations and DNA integrity assay ( DIA ) , showed a sensitivity of 52 % for CRC detection and a specificity of 94 % in average-risk individuals . The present study was conducted to determine the sensitivity and specificity of a second-generation assay ( version 2 ) that uses improved DNA stabilization/isolation techniques and a new promoter methylation marker . METHODS Forty patients with CRC and 122 subjects with normal colonoscopy provided stool sample s to which DNA preservation buffer was added immediately . DNA was purified using gel-based capture , and analyzed for the original panel of 22 mutations , DIA , and 2 new promoter methylation markers . RESULTS By using DNA that was optimally preserved and purified from stool , the sensitivity of the prototype version 1 assay increased to 72.5 % because of enhanced performance of DIA . Vimentin gene methylation alone provided sensitivity and specificity of 72.5 % and 86.9 % , respectively . The optimal combination of vimentin methylation plus DIA result ed in 87.5 % sensitivity and 82 % specificity ; cancers were detected regardless of stage or location . False-positive vimentin methylation was associated with older age . CONCLUSIONS An improved fecal DNA test that incorporates only 2 markers shows much higher sensitivity for CRC . The new assay is easier to perform and should be less costly , thereby facilitating its use for noninvasive CRC screening OBJECTIVES To determine if participation in colorectal cancer screening using faecal occult blood testing ( FOBT ) is affected by a restrictive diet and if it is associated with certain demographic variables . PARTICIPANTS AND SETTING 1,203 residents of South Australia aged 50 - 69 years , with no " currently active bowel disease " , r and omly selected from a data base of people willing to be contacted about unspecified health issues . DESIGN R and omised controlled trial : participants were offered screening by immunochemical FOBT by mail in 1998 . Half were r and omly allocated to a group instructed to follow a low-peroxidase diet , as required for guaiac FOBT , while the other group was not so restricted . MAIN OUTCOME MEASURES Effect of diet restriction on participation ( return of correctly completed FOBT sample cards within 15 weeks ) ; time taken to return cards ; relationships between participation and demographic variables . RESULTS Participation rates were 65.9 % ( no-diet group ) and 53.3 % ( diet group ) ( difference , 12.6 % ; 95 % CI , 7.1%-18.1 % ) . In the first week , rates of return as a proportion of all tests returned were 13.1 % ( no-diet ) and 1.6 % ( diet ) ( difference , 11.5 % ; 95 % CI , 8.6%-14.4 % ) , increasing to 54.3 % and 44.5 % , respectively , after five weeks ( difference , 9.8 % ; 95 % CI , 4.2%-15.4 % ) . Participation was significantly associated with older age ( odds ratio , 1.40 ; 95 % CI , 1.10 - 1.78 ) , but not sex , Index of Social Disadvantage or rural versus urban address . CONCLUSIONS Dietary restrictions create a barrier to FOBT-based screening for colorectal cancer . The use of immunochemical rather than guaiac FOBT removes this barrier Colorectal cancer is the second-leading cause of cancer death . New noninvasive options for screening capable of diagnosing cancer at an early stage are needed to improve compliance and reduce mortality . This study was design ed to provide an estimate of the sensitivity and specificity of a multitarget assay panel ( MTAP ) of stool DNA changes . Eighty patients with advanced colorectal neoplasia and 212 control subjects provided stool sample s before colonoscopy . Patients with hereditary colorectal cancer syndromes were excluded . The MTAP included 21 specific mutations in the adenomatous polyposis coli ( APC ) , p53 , and K-ras genes , a microsatellite instability marker ( BAT-26 ) , and a marker of abnormal apoptosis ( DNA Integrity Assay ) . All sample s were analyzed in the clinical laboratory at EXACT Sciences . Multitarget assay panel detected 33 of 52 patients ( 63.5 % , 95 % confidence interval [ CI ] , 49.0%-76.4 % ) with invasive colorectal cancer , including 26 of 36 ( 72.2 % ) with node-negative disease ( American Joint Committee on Cancer [ AJCC ] stage I/II ) and 7 of 16 ( 43.7 % ) with advanced disease ( AJCC stage III/IV ) . Sixteen of 28 patients ( 57.1 % ; 95 % CI , 37.2%-75.5 % ) with advanced adenomas ( lesions containing high- grade dysplasia , villous adenomas , or tubular adenomas > 1 cm in size ) were detected , including 6 of 7 ( 85.7 % ) with high- grade dysplasia and 10 of 21 ( 47.6 % ) with other advanced adenomas . Specificity was 96.2 % ( 95 % CI , 92.7%-98.4 % ) in patients with either no colorectal lesions or diminutive polyps . Multitarget assay panel has better sensitivity than that reported with use of Hemoccult(R ) II in fecal occult blood testing , with similar specificity . Sensitivity appeared to be equally high for patients with node-negative and advanced disease , as well as for advanced adenomas . This study contained a disproportionately high number of distal cancers and , as such , may not be representative of results in proximal lesions . Although a prospect i ve study in an average-risk population is needed to vali date these findings , MTAP may offer an important noninvasive option for population -based screening BACKGROUND Although fecal occult-blood testing is the only available noninvasive screening method that reduces the risk of death from colorectal cancer , it has limited sensitivity . We compared an approach that identifies abnormal DNA in stool sample s with the Hemoccult II fecal occult-blood test in average-risk , asymptomatic persons 50 years of age or older . METHODS Eligible subjects su bmi tted one stool specimen for DNA analysis , underwent st and ard Hemoccult II testing , and then underwent colonoscopy . Of 5486 subjects enrolled , 4404 completed all aspects of the study . A subgroup of 2507 subjects was analyzed , including all those with a diagnosis of invasive adenocarcinoma or advanced adenoma plus r and omly chosen subjects with no polyps or minor polyps . The fecal DNA panel consisted of 21 mutations . RESULTS The fecal DNA panel detected 16 of 31 invasive cancers , whereas Hemoccult II identified 4 of 31 ( 51.6 percent vs. 12.9 percent , P=0.003 ) . The DNA panel detected 29 of 71 invasive cancers plus adenomas with high- grade dysplasia , whereas Hemoccult II identified 10 of 71 ( 40.8 percent vs. 14.1 percent , P<0.001 ) . Among 418 subjects with advanced neoplasia ( defined as a tubular adenoma at least 1 cm in diameter , a polyp with a villous histologic appearance , a polyp with high- grade dysplasia , or cancer ) , the DNA panel was positive in 76 ( 18.2 percent ) , whereas Hemoccult II was positive in 45 ( 10.8 percent ) . Specificity in subjects with negative findings on colonoscopy was 94.4 percent for the fecal DNA panel and 95.2 percent for Hemoccult II . CONCLUSIONS Although the majority of neoplastic lesions identified by colonoscopy were not detected by either noninvasive test , the multitarget analysis of fecal DNA detected a greater proportion of important colorectal neoplasia than did Hemoccult II without compromising specificity BACKGROUND One type of fecal occult blood test ( FOBT ) , the unrehydrated guaiac fecal occult blood test ( GT ) , is recommended by the United States Preventive Services Task Force and the Institute of Medicine for use in screening programs , but it has relatively low sensitivity as a single test for detecting advanced colonic neoplasms ( cancer and adenomatous polyps > or = 1 cm in diameter ) . Thus , improving the sensitivity of FOBT should make colon cancer screening programs that use these tests more effective . METHODS We assessed prospect ively the performance characteristics of two newer FOBTs in 5841 subjects at average risk for colorectal cancer in a large group-model managed care organization . The tests evaluated included a sensitive GT , a fecal immunochemical test ( FIT ) , and the combination of both tests . Patients with positive and negative test results were advised to have colonoscopy and sigmoidoscopy , respectively . Sensitivity and specificity for detecting advanced neoplasms in the left colon within 2 years after the FOBT screening were evaluated for the two tests administered separately and in combination . RESULTS A total of 139 patients were diagnosed with advanced colorectal neoplasms ( n = 14 cancers , n = 128 adenomas ) within the 2 years following their initial FOBT screening . Sensitivity for detecting cancer was 81.8 % ( 95 % confidence interval [ CI ] = 47.8 % to 96.8 % ) for the FIT alone and 64.3 % ( 95 % CI = 35.6 % to 86.0 % ) for the sensitive GT and the combination test . Sensitivity for detecting advanced colorectal adenomas was 41.3 % ( 95 % CI = 32.7 % to 50.4 % ) for the sensitive GT , 29.5 % ( 95 % CI = 21.4 % to 38.9 % ) for the FIT , and 22.8 % ( 95 % CI = 16.1 % to 31.3 % ) for the combination test . Specificity for detecting cancer and adenomas was 98. Output:	Conclusion On the basis of the available ( albeit limited ) evidence , while fDNA is cost-effective when compared with no screening , it is currently dominated by most of the other available screening options . Cost and test performance appear to be the main influences on cost-effectiveness
MS212060	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Treatment with low-dose amphotericin B ( 0.4 mg per kilogram of body weight per day ) or oral azole therapy in patients with the acquired immunodeficiency syndrome ( AIDS ) and cryptococcal meningitis has been associated with high mortality and low rates of cerebrospinal fluid sterilization . METHODS In a double-blind multicenter trial we r and omly assigned patients with a first episode of AIDS-associated cryptococcal meningitis to treatment with higher-dose amphotericin B ( 0.7 mg per kilogram per day ) with or without flucytosine ( 100 mg per kilogram per day ) for two weeks ( step one ) , followed by eight weeks of treatment with itraconazole ( 400 mg per day ) or fluconazole ( 400 mg per day ) ( step two ) . Treatment was considered successful if cerebrospinal fluid cultures were negative at 2 and 10 weeks or if the patient was clinical ly stable at 2 weeks and asymptomatic at 10 weeks . RESULTS At two weeks , the cerebrospinal fluid cultures were negative in 60 percent of the 202 patients receiving amphotericin B plus flucytosine and in 51 percent of the 179 receiving amphotericin B alone ( P=0.06 ) . Elevated intracranial pressure was associated with death in 13 of 14 patients during step one . The clinical outcome did not differ significantly between the two groups . Seventy-two percent of the 151 fluconazole recipients and 60 percent of the 155 itraconazole recipients had negative cultures at 10 weeks ( 95 percent confidence interval for the difference in percentages , -100 to 21 ) . The proportion of patients who had clinical responses was similar with fluconazole ( 68 percent ) and itraconazole ( 70 percent ) . Overall mortality was 5.5 percent in the first two weeks and 3.9 percent in the next eight weeks , with no significant difference between the groups . In a multivariate analysis , the addition of flucytosine during the initial two weeks and treatment with fluconazole for the next eight weeks were independently associated with cerebrospinal fluid sterilization . CONCLUSIONS For the initial treatment of AIDS-associated cryptococcal meningitis , the use of higher-dose amphotericin B plus flucytosine is associated with an increased rate of cerebrospinal fluid sterilization and decreased mortality at two weeks , as compared with regimens used in previous studies . Although consolidation therapy with fluconazole is associated with a higher rate of cerebrospinal fluid sterilization , itraconazole may be a suitable alternative for patients unable to take fluconazole Background Cryptococcus is the most common cause of adult meningitis in Africa . We evaluated the activity of adjunctive sertraline , previously demonstrated to have in vitro and in vivo activity against Cryptococcus . Methods We enrolled 172 HIV-infected Ug and ans with cryptococcal meningitis from August 2013 through August 2014 into an open-label dose-finding study to assess safety and microbiologic efficacy . Sertraline 100–400mg/day was added to st and ard therapy of amphotericin + fluconazole 800mg/day . We evaluated early fungicidal activity via Cryptococcus cerebrospinal fluid ( CSF ) clearance rate , sertraline pharmacokinetics , and in vitro susceptibility . Findings Participants receiving any sertraline dose averaged a CSF clearance rate of −0·37 ( 95%CI : −0·41 , −0·33 ) colony forming units (CFU)/mL/day . Incidence of paradoxical immune reconstitution inflammatory syndrome ( IRIS ) was 5 % ( 2/43 ) and relapse was 0 % through 12-weeks . Sertraline reached steady state concentrations in plasma by day 7 , with median steady-state concentrations of 201 ng/mL ( IQR , 90–300 ; n=49 ) with 200mg/day and 399 ng/mL ( IQR , 279–560 ; n=30 ) with 400mg/day . Plasma concentrations reached 83 % of steady state levels by day 3 . The median projected steady state brain tissue concentration at 200mg/day was 3·7 ( IQR , 2·0–5·7 ) mcg/mL and 6·8 ( IQR , 4·6–9·7 ) mcg/mL at 400mg/day . Minimum inhibitory concentrations were ≤2 mcg/mL for 27 % ( 35/128 ) , ≤4 mcg/mL for 84 % ( 108/128 ) , ≤6 mcg/mL for 91 % ( 117/128 ) , and ≤8 mcg/mL for 100 % of 128 Cryptococcus isolates . Interpretation Sertraline had faster cryptococcal CSF clearance , decreased IRIS , and decreased relapse compared with historical experiences . Sertraline reaches therapeutic levels in a clinical setting . This inexpensive and off-patent oral medication is a promising adjunctive antifungal therapy . Funding National Institutes of Health , Gr and Challenges Canada BACKGROUND Cryptococcal meningitis accounts for more than 100,000 human immunodeficiency virus (HIV)–related deaths per year . We tested two treatment strategies that could be more sustainable in Africa than the st and ard of 2 weeks of amphotericin B plus flucytosine and more effective than the widely used fluconazole monotherapy . METHODS We r and omly assigned HIV‐infected adults with cryptococcal meningitis to receive an oral regimen ( fluconazole [ 1200 mg per day ] plus flucytosine [ 100 mg per kilogram of body weight per day ] for 2 weeks ) , 1 week of amphotericin B ( 1 mg per kilogram per day ) , or 2 weeks of amphotericin B ( 1 mg per kilogram per day ) . Each patient assigned to receive amphotericin B was also r and omly assigned to receive fluconazole or flucytosine as a partner drug . After induction treatment , all the patients received fluconazole consolidation therapy and were followed to 10 weeks . RESULTS A total of 721 patients underwent r and omization . Mortality in the oral‐regimen , 1‐week amphotericin B , and 2‐week amphotericin B groups was 18.2 % ( 41 of 225 ) , 21.9 % ( 49 of 224 ) , and 21.4 % ( 49 of 229 ) , respectively , at 2 weeks and was 35.1 % ( 79 of 225 ) , 36.2 % ( 81 of 224 ) , and 39.7 % ( 91 of 229 ) , respectively , at 10 weeks . The upper limit of the one‐sided 97.5 % confidence interval for the difference in 2‐week mortality was 4.2 percentage points for the oral‐regimen group versus the 2‐week amphotericin B groups and 8.1 percentage points for the 1‐week amphotericin B groups versus the 2‐week amphotericin B groups , both of which were below the predefined 10‐percentage‐point noninferiority margin . As a partner drug with amphotericin B , flucytosine was superior to fluconazole ( 71 deaths [ 31.1 % ] vs. 101 deaths [ 45.0 % ] ; hazard ratio for death at 10 weeks , 0.62 ; 95 % confidence interval [ CI ] , 0.45 to 0.84 ; P=0.002 ) . One week of amphotericin B plus flucytosine was associated with the lowest 10‐week mortality ( 24.2 % ; 95 % CI , 16.2 to 32.1 ) . Side effects , such as severe anemia , were more frequent with 2 weeks than with 1 week of amphotericin B or with the oral regimen . CONCLUSIONS One week of amphotericin B plus flucytosine and 2 weeks of fluconazole plus flucytosine were effective as induction therapy for cryptococcal meningitis in re source ‐limited setting s. ( ACTA Current Controlled Trials number , IS RCT N45035509 . Objective : HIV-infected patients with treated cryptococcal meningitis are at risk for further neurological deterioration after commencing combination antiretroviral therapy ( cART ) , mostly because of cryptococcosis-associated immune reconstitution inflammatory syndrome ( C-IRIS ) . Identifying predictors of C-IRIS could enable risk stratification . Design : Prospect i ve , longitudinal cohort study for 24 weeks . Setting : Durban , South Africa . Participants : One hundred and thirty HIV-infected patients with first cryptococcal meningitis episode Intervention : Antifungal therapy ( amphotericin 1 mg/kg median 14 days , followed by consolidation and maintenance fluconazole ) and cART ( commenced median of 18 days from cryptococcal meningitis diagnosis ) . Main outcome measure : Clinical , blood , and cerebrospinal fluid ( CSF ) markers associated with C-IRIS before and during cART and clinical significance of CSF cryptococcal culture negativity pre-cART commencement . Results : Of 106 patients commencing cART , 27 ( 25.5 % ) developed C-IRIS , 16 ( 15.1 % ) neurological deterioration-not C-IRIS , and 63 ( 59.4 % ) no neurological deterioration . On multivariable analysis , C-IRIS was associated with persistent CSF cryptococcal growth [ hazard ratio ( HR ) 0.27 , P = 0.026 ] and lower CSF protein ( HR 0.53 , P = 0.059 ) prior to cART and lower CD4 + T-cell increases ( HR 0.99 , P = 0.026 ) but not change in HIV viral load during cART . Using survival analysis , patients with a negative cryptococcal culture pre-cART commencement ( n = 51 ; 48.1 % ) experienced fewer episodes of neurological deterioration , C-IRIS , and cryptococcal relapse/persistence than patients with culture positivity ( n = 55 ; 51.9 % , HR 0.33 , 0.33 , and 0.12 and P = 0.0003 , 0.0042 , and 0.0004 , respectively ) . Conclusion : Persistent CSF cryptococcal growth at cART initiation and poor CD4 + T-cell increases on cART are strong predictors of C-IRIS . Approaches aim ed at achieving CSF culture negativity prior to cART should be evaluated as a strategy to reduce rates of C-IRIS David Boulware and colleagues investigate clinical features in a prospect i ve cohort with AIDS and recent cryptococcal meningitis after initiation of antiretroviral therapy to identify biomarkers for prediction and diagnosis of CM-IRIS ( cryptococcal meninigitis-related immune reconstitution inflammatory syndrome ) Background . Amphotericin-based combination antifungal therapy reduces mortality from human immunodeficiency virus (HIV)-associated cryptococcal meningitis . However , 40%–50 % of individuals have positive cerebrospinal fluid ( CSF ) fungal cultures at completion of 2 weeks of amphotericin induction therapy . Residual CSF culture positivity has historically been associated with poor clinical outcomes . We investigated whether persistent CSF fungemia was associated with detrimental clinical outcomes in a contemporary African cohort . Methods . Human immunodeficiency virus-infected individuals with cryptococcal meningitis in Ug and a and South Africa received amphotericin ( 0.7–1.0 mg/kg per day ) plus fluconazole ( 800 mg/day ) for 2 weeks , followed by “ enhanced consolidation ” therapy with fluconazole 800 mg/day for at least 3 weeks or until cultures were sterile , and then 400 mg/day for 8 weeks . Participants were r and omized to receive antiretroviral therapy ( ART ) either 1–2 or 5 weeks after diagnosis and observed for 6 months . Survivors were classified as having sterile or nonsterile CSF based on 2-week CSF cultures . Mortality , immune reconstitution inflammatory syndrome ( IRIS ) , and culture-positive relapse were compared in those with sterile or nonsterile CSF using Cox regression . Results . Of 132 participants surviving 2 weeks , 57 % had sterile CSF at 2 weeks , 23 died within 5 weeks , and 40 died within 6 months . Culture positivity was not significantly associated with mortality ( adjusted 6-month hazard ratio , 1.2 ; 95 % confidence interval , 0.6–2.3 ; P = .28 ) . Incidence of IRIS or relapse was also not significantly related to culture positivity . Conclusions . Among patients , all treated with enhanced consolidation antifungal therapy and ART , residual cryptococcal culture positivity was Output:	Currently recommended fluconazole doses may be inadequate for cryptococcosis .
MS212061	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE This study presents a cost-minimisation analysis of moxifloxacin compared to combination treatment with levofloxacin and ceftriaxone in patients hospitalised with community-acquired pneumonia ( CAP ) in Germany . RESEARCH DESIGN AND METHODS In the MOTIV study , 738 adult patients with CAP requiring hospitalisation and initial parenteral antibiotic therapy were r and omised to sequential IV/oral therapy with either moxifloxacin ( n = 368 ) , or levofloxacin and ceftriaxone ( n = 365 ) . The primary effectiveness endpoint was the proportion of patients demonstrating clinical improvement 5 - 7 days after the completion of study treatment . Subgroup analysis considered patients with severe CAP according to pneumonia severity index ( PSI ) risk class IV and V , microbiologically proven infection , a history of chronic obstructive pulmonary disease , and a history of cardiovascular disease . The analysis included the cost of study medication , hospital stay , readmission and inpatient procedures and diagnostics . Event frequency in the study was multiplied by German unit costs to estimate per-patient expenditure . The analysis was conducted from a hospital perspective . Sensitivity analysis investigated the effect of costing from an insurer perspective . RESULTS No significant difference was found in the percentage of successfully treated patients . Average per patient cost was euro 2190 for the moxifloxacin group , and euro 2619 for the levofloxacin + ceftriaxone group ( difference -euro 430 , 95 % CI : -euro 138 , -euro 740 ; p < 0.05 ) . Variability in total costs was wide , with some patients accruing up to euro 18,000 . Medication cost was significantly lower with moxifloxacin than levofloxacin + ceftriaxone ( -euro 470 , 95 % CI : -euro 522 , -euro 421 ) , and accounted for between 15 and 30 % of total costs . CONCLUSIONS In this analysis of patients hospitalised with CAP in Germany , treatment with moxifloxacin was significantly less costly than treatment with levofloxacin and ceftriaxone Current World Health Organization ( WHO ) guidelines for severe pneumonia treatment of under-5 children recommend hospital referral . However , high treatment cost is a major barrier for communities . We compared household costs for referred cases with management by lady health workers ( LHWs ) using oral antibiotics . This study was nested within a cluster r and omized trial in Haripur , Pakistan . Data on direct and indirect costs were collected through interviews and record review s in the 14 intervention and 14 control clusters . The average household cost/case for a LHW managed case was $ 1.46 compared with $ 7.60 for referred cases . When the cost of antibiotics provided by the LHW program was excluded from the estimates , the cost/case came to $ 0.25 and $ 7.51 for the community managed and referred cases , respectively , a 30-fold difference . Exp and ing severe pneumonia treatment with oral amoxicillin to community level could significantly reduce household costs and improve access to the underprivileged population , preventing many child deaths Background Knowledge of treatment cost is essential in assessing cost effectiveness in healthcare . Evidence of the potential impact of implementing available interventions against childhood illnesses in developing countries challenges us to define the costs of treating these diseases . The purpose of this study is to describe the total costs associated with treatment of pneumonia , malaria and meningitis in children less than five years in seven Kenyan hospitals . Methods Patient re source use data were obtained from largely prospect i ve evaluation of medical records and household expenditure during illness was collected from interviews with caretakers . The estimates for costs per bed day were based on published data . A sensitivity analysis was conducted using WHO-CHOICE values for costs per bed day . Results Treatment costs for 572 children ( pneumonia = 205 , malaria = 211 , meningitis = 102 and mixed diagnoses = 54 ) and household expenditure for 390 households were analysed . From the provider perspective the mean cost per admission at the national hospital was US $ 95.58 for malaria , US $ 177.14 for pneumonia and US $ 284.64 for meningitis . In the public regional or district hospitals the mean cost per child treated ranged from US $ 47.19 to US $ 81.84 for malaria and US $ 54.06 to US $ 99.26 for pneumonia . The corresponding treatment costs in the mission hospitals were between US $ 43.23 to US $ 88.18 for malaria and US $ 43.36 to US $ 142.22 for pneumonia . Meningitis was treated for US $ 189.41 at the regional hospital and US $ 201.59 at one mission hospital . The total treatment cost estimates were sensitive to changes in the source of bed day costs . The median treatment related household payments within quintiles defined by total household expenditure differed by type of facility visited . Public hospitals recovered up to 40 % of provider costs through user charges while mission facilities recovered 44 % to 100 % of costs . Conclusion Treatments cost for inpatient malaria , pneumonia and meningitis vary by facility type , with mission and tertiary referral facilities being more expensive compared to primary referral . Households of sick children contribute significantly towards provider cost through payment of user fees . These findings could be used in cost effectiveness analysis of health interventions Background : Practice guidelines suggest that all patients hospitalised with community-acquired pneumonia ( CAP ) should receive antibiotics within 4 h of admission . An audit at our hospital during 1999–2000 showed that this target was achieved in less than two thirds of patients with severe CAP . Methods : An experienced multidisciplinary steering group design ed a management pathway to improve the early delivery of appropriate antibiotics to patients with CAP . This was implemented using a multifaceted strategy . The effect of implementation was evaluated using a controlled before- and -after study design over two winter seasons ( November – April 2001–2 and 2002–3 ) . Cost-effectiveness analyses were performed from the hospital ’s perspective . Results : The proportion of patients receiving appropriate antibiotics within 4 h of admission to hospital increased from 33 % to 56 % at the intervention site , and from 32 % to 36 % at the control site ( absolute change adjusted for differences in severity of illness 17 % , p = 0.035 ) . The cost per additional patient receiving appropriate antibiotics within 4 h was £ 132 with no post-implementation evaluation , and £ 456 for a limited post-implementation evaluation . Simple modelling from the results of a large observational study suggests that the cost per death prevented could be £ 3003 with no post-implementation evaluation , or £ 16 632 with a limited post-implementation evaluation . Conclusions : The intervention markedly improved door-to-antibiotic time , albeit at considerable cost . It might still be a cost-effective strategy , however , to reduce mortality in CAP . Uncertainty about the cost effectiveness of such interventions is likely to be resolved only by a well- design ed , cluster r and omised trial Background Clinical efficacy of antibiotics may be affected by changes in the susceptibility of microorganisms to antimicrobial agents . The purpose of this study is to assess how these changes could affect the initial efficacy of ertapenem and ceftriaxone in the treatment of community-acquired pneumonia ( CAP ) in elderly patients and the potential consequences this may have in health care costs . Methods Initial efficacy in elderly was obtained from a combined analysis of two multicenter , r and omized studies . An alternative scenario was carried out using initial efficacy data according to the pneumonia severity index ( PSI ) . Country-specific pathogens distribution was obtained from a national epidemiological study , and microbiological susceptibilities to first- and second-line therapies were obtained from Spanish or European surveillance studies . A decision analytic model was used to compare ertapenem versus ceftriaxone for CAP inpatient treatment . Inputs of the model were the expected effectiveness previously estimated and re source use considering a Spanish national health system perspective . Outcomes include difference in proportion of successfully treated patients and difference in total costs between ertapenem and ceftriaxone . The model performed one-way and probabilistic sensitivity analyses . Results First-line treatment of CAP with ertapenem led to a higher proportion of successfully treated patients compared with ceftriaxone in Spain . One-way sensitivity analysis showed that length of stay was the key parameter of the model . Probabilistic sensitivity analysis showed that ertapenem can be a cost-saving strategy compared with ceftriaxone , with a 59 % probability of being dominant ( lower costs with additional health benefits ) for both , elderly patients ( > 65 years ) and patients with PSI > 3 . Conclusion The incorporation of the current antimicrobial susceptibility into the initial clinical efficacy has a significant impact in outcomes and costs in CAP treatment . The treatment with ertapenem compared with ceftriaxone result ed in better clinical outcomes and lower treatment costs for two segments of the Spanish population : elderly patients and patients with severe pneumonia ( PSI > 3 ) Background : Pneumonia is one of the leading causes of morbidity and mortality among children in many developing countries . It is reported that 12.9 million children under 5 years of age died world-wide in 1990 and one-third of these deaths or 4.3 million annually were attributed to acute respiratory infection with pneumonia . Objectives : On this basis , a study was conducted in a district hospital to study the therapy outcomes of antibiotic regimens used in pediatric community-acquired pneumonia ( CAP ) management and to conduct a cost-effectiveness analysis ( CE ) between IV ampicillin versus combination therapy of IV ampicillin and IV gentamicin . Method : A prospect i ve , r and omized , controlled , single blind study was conducted in a pediatric ward in a 80-bed district hospital . Pediatric patients diagnosed with CAP aged 2 months to 5 years old were r and omly and equally divided into two treatment arms : ampicillin versus ampicillin plus gentamicin . The dose of IV ampicillin used in this study was 100 mg/kg/day divided every 6 h and 5 mg/kg of IV gentamicin as a single daily dose . Both clinical and economic evaluations were carried out to compare both treatment arms . Results : With the inclusion and exclusion criteria , only 40 patients diagnosed with CAP were included in the study . The results showed that the two treatment arms were significantly different ( P < 0.05 ) in terms of duration of patients on ampicillin , number of days of hospitalization and time to switch to oral therapy . A significant difference was noted between the two treatment modalities in terms of effectiveness and cost ( P < 0.05 ) . Conclusion : Overall , the endpoint of this study showed that the total cost per patient of ampicillin-treated group is cheaper than the total cost with the combination therapy ( ampicillin plus gentamicin ) and reduced unnecessary exposure to adverse effects or toxicities . Besides that , addition of gentamicin in the treatment modalities will only increase the cost of treatment without introducing any changes in the treatment outcome Background To determine the cost-effectiveness of strategies of preferred antibiotic treatment with beta-lactam/macrolide combination or fluoroquinolone monotherapy compared to beta-lactam monotherapy . Methods Costs and effects were estimated using data from a cluster-r and omized cross-over trial of antibiotic treatment strategies , primarily from the reduced third payer perspective ( i.e. hospital admission costs ) . Cost-minimization analysis ( CMA ) and cost-effectiveness analysis ( CEA ) were performed using linear mixed models . CMA results were expressed as difference in costs per patient . CEA results were expressed as incremental cost-effectiveness ratios ( ICER ) showing additional costs per prevented death . Results A total of 2,283 patients were included . Crude average costs within 90 days from the reduced third payer perspective were € 4,294 , € 4,392 , and € 4,002 per patient for the beta-lactam monotherapy , beta-lactam/macrolide combination , and fluoroquinolone monotherapy strategy , respectively . CMA results were € 106 ( 95 % CI € -697 to € 754 ) for the beta-lactam/macrolide combination strategy and € -278 ( 95%CI € -991 to € 396 ) for the fluoroquinolone monotherapy strategy , both compared to the beta-lactam monotherapy strategy . The ICER was not statistically significantly different between the strategies . Other perspectives yielded similar results . Conclusions There were no significant differences in cost-effectiveness of strategies of preferred antibiotic treatment of CAP on non-ICU wards with either beta-lactam monotherapy , beta-lactam/macrolide combination therapy , or fluoroquinolone monotherapy . Trial registration The trial was registered with Clinical Trials.gov , number NCT01660204 , on May 2nd , 2012 OBJECTIVE To examine treatment costs of community-acquired pneumonia ( CAP ) in adult out patients given oral ( p.o . ) levofloxacin or cefuroxime axetil as initial therapy . STUDY DESIGN Patients with a primary diagnosis of CAP were enrolled in a multicenter , prospect i ve , r and omized , open-label , active-controlled Phase III clinical trial . Both in patients and out patients were assigned to 1 of 2 treatment groups : ( 1 ) intravenous ( i.v . ) or p.o . levofloxacin ; or ( 2 ) i.v . ceftriaxone and /or p.o . cefuroxime axetil . METHODS To make legitimate and meaningful cost comparisons between similar types of patients receiving dru Output:	Economic evaluation of interventions for management of CAP to date supports cost-effectiveness of studied interventions . However , evidence relates largely to antimicrobials choice in older population s in developed countries .
MS212062	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background The efficacy of disease management programs in improving the outcome of heart failure patients remains uncertain and may vary across health systems . This study explores whether a countrywide disease management program is superior to usual care in reducing adverse health outcomes and improving well-being among community-dwelling adult patients with moderate-to-severe chronic heart failure who have universal access to advanced health-care services and technologies . Methods In this multicenter open-label trial , 1,360 patients recruited after hospitalization for heart failure exacerbation ( 38 % ) or from the community ( 62 % ) were r and omly assigned to either disease management or usual care . Disease management , delivered by multi-disciplinary teams , included coordination of care , patient education , monitoring disease symptoms and patient adherence to medication regimen , titration of drug therapy , and home tele-monitoring of body weight , blood pressure and heart rate . Patients assigned to usual care were treated by primary care practitioners and consultant cardiologists . The primary composite endpoint was the time elapsed till first hospital admission for heart failure exacerbation or death from any cause . Secondary endpoints included the number of all hospital admissions , health-related quality of life and depression during follow-up . Intention-to-treat comparisons between treatments were adjusted for baseline patient data and study center . Results During the follow-up , 388 ( 56.9 % ) patients assigned to disease management and 387 ( 57.1 % ) assigned to usual care had a primary endpoint event . The median ( range ) time elapsed until the primary endpoint event or end of study was 2.0 ( 0–5.0 ) years among patients assigned to disease management , and 1.8 ( 0–5.0 ) years among patients assigned to usual care ( adjusted hazard ratio , 0.908 ; 95 % confidence interval , 0.788 to 1.047 ) . Hospital admissions were mostly ( 70 % ) unrelated to heart failure . Patients assigned to disease management had a better health-related quality of life and a lower depression score during follow-up . Conclusions This comprehensive disease management intervention was not superior to usual care with respect to the primary composite endpoint , but it improved health-related quality of life and depression . A disease-centered approach may not suffice to make a significant impact on hospital admissions and mortality in patients with chronic heart failure who have universal access to health care . Clinical trial registration Clinical trials.gov identifier : NCT00533013 . Trial registration date : 9 August 2007 . Initial protocol release date : 20 September 2007 Abstract Background : Disease management programmes ( DMPs ) improve quality of care for patients with heart failure ( HF ) . However , only a limited number of trials have studied the efficacy of such programmes for patients with heart failure with preserved ejection fraction ( HFPEF ) . Objective : To estimate the impact of a structured , nurse-led patient education programme and care plan in general practice on outcome parameters and events in patients with HFPEF . Methods : Single blinded r and omized clinical trial with an intervention over six months and a follow-up during 12 additional months . In the control group , the patients ( n = 41 ) were managed according to Russian national guidelines . Patients in the intervention group ( n = 44 ) received education on individual lifestyle changes and modifications of cardiovascular disease ( CVD ) risk factors , home-based exercise training and weekly nurse consultations in addition to usual care . Results : Six months after their inclusion , patients in the intervention group significantly improved body mass index , waist circumference , six-min walk test distance , total cholesterol , low-density lipoprotein , left ventricular end-diastolic volume index , quality of life and level of anxiety . After 18 months , there were 11 deaths ( 25 % ) or hospitalizations in the intervention group and 12 ( 29 % ) in the control group ( P = 0.134 ) . Cardiovascular mortality and readmission rate were not reduced significantly after six months of follow-up : the hazard ratio was 0.47 ( 95 % CI : 0.17–1.28 ; P = 0.197 ) . After 18 months , this was 0.85 ( 0.42–1.73 ; P = 0.658 ) . Conclusion : This primary care based DMP for patients with HFPEF improved the patients ’ emotional status and quality of life , positively influenced body weight , functional capacity and lipid profile , and attenuated heart remodelling Importance Many patients with chronic heart failure experience reduced health status despite receiving conventional therapy . Objective To determine whether a symptom and psychosocial collaborative care intervention improves heart failure – specific health status , depression , and symptom burden in patients with heart failure . Design , Setting , and Participants A single-blind , 2-arm , multisite r and omized clinical trial was conducted at Veterans Affairs , academic , and safety-net health systems in Colorado among out patients with symptomatic heart failure and reduced health status recruited between August 2012 and April 2015 . Data from all participants were included regardless of level of participation , using an intent-to-treat approach . Interventions Patients were r and omized 1:1 to receive the Collaborative Care to Alleviate Symptoms and Adjust to Illness ( CASA ) intervention or usual care . The CASA intervention included collaborative symptom care provided by a nurse and psychosocial care provided by a social worker , both of whom worked with the patients ’ primary care clinicians and were supervised by a study primary care clinician , cardiologist , and palliative care physician . Main Outcomes and Measures The primary outcome was patient-reported heart failure – specific health status , measured by difference in change scores on the Kansas City Cardiomyopathy Question naire ( range , 0 - 100 ) at 6 months . Secondary outcomes included depression ( measured by the 9-item Patient Health Question naire ) , anxiety ( measured by the 7-item Generalized Anxiety Disorder Question naire ) , overall symptom distress ( measured by the General Symptom Distress Scale ) , specific symptoms ( pain , fatigue , and shortness of breath ) , number of hospitalizations , and mortality . Results Of 314 patients r and omized ( 157 to intervention arm and 157 to control arm ) , there were 67 women and 247 men , mean ( SD ) age was 65.5 ( 11.4 ) years , and 178 ( 56.7 % ) had reduced ejection fraction . At 6 months , the mean Kansas City Cardiomyopathy Question naire score improved 5.5 points in the intervention arm and 2.9 points in the control arm ( difference , 2.6 ; 95 % CI , –1.3 to 6.6 ; P = .19 ) . Among secondary outcomes , depressive symptoms and fatigue improved at 6 months with CASA ( effect size of –0.29 [ 95 % CI , –0.53 to –0.04 ] for depressive symptoms and –0.30 [ 95 % CI , –0.55 to –0.06 ] for fatigue ; P = .02 for both ) . There were no significant changes in overall symptom distress , pain , shortness of breath , or number of hospitalizations . Mortality at 12 months was similar in both arms ( 10 patients died receiving CASA , and 13 patients died receiving usual care ; P = .52 ) . Conclusions and Relevance This multisite r and omized clinical trial of the CASA intervention did not demonstrate improved heart failure – specific health status . Secondary outcomes of depression and fatigue , both difficult symptoms to treat in heart failure , improved . Trial Registration clinical trials.gov Identifier : Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more To determine the reliability and validity of a patient outcome question naire for chronic heart failure , a r and omized , double-blind , placebo-controlled , 3-month trial of pimobendan , an investigational medication with inotropic and vasodilator activities , was performed . Evaluated were 198 ambulatory patients with primarily New York Heart Association ( NYHA ) class III heart failure from 20 referral centers . Baseline therapy included digoxin , diuretics and , in 80 % , a converting enzyme inhibitor . Oral pimobendan at 2.5 ( n = 49 ) , 5.0 ( n = 51 ) , or 10 ( n = 49 ) mg daily or matching placebo ( n = 49 ) was administered . The Minnesota Living with Heart Failure ( LIhFE ) question naire was a primary outcome measure , along with an exercise test . Interitem correlations identified subgroups of questions representing physical and emotional dimensions . Repeated baseline scores were highly correlated ( r = 0.93 ) , as were the physical ( r = 0.89 ) and emotional ( r = 0.88 ) dimension scores . Placebo did not have a significant effect with median ( 25th , 75th percentile ) changes from baseline scores of 1 ( -3 , 5 ) , 1 ( -2 , 3 ) , and 0 ( -1 , 2 ) , respectively ( all p values greater than 0.10 ) . The 5 mg dose significantly improved the total score , 7.5 ( 0 , 18 ; p = 0.01 ) and the physical dimension , 4 ( 0 , 8 ; p = 0.01 ) , compared with placebo . Changes in the total ( r = 0.33 ; p less than 0.01 ) and physical ( r = 0.35 ; p less than 0.01 ) scores were weakly related to changes in exercise times , but corresponded well with changes in patients ' ratings of dyspnea and fatigue . ( ABSTRACT TRUNCATED AT 250 WORDS IMPORTANCE Heart failure ( HF ) has a major effect on patients ' health status , including their symptom burden , functional status , and health-related quality of life . OBJECTIVE To determine the effectiveness of a collaborative care patient-centered disease management ( PCDM ) intervention to improve the health status of patients with HF . DESIGN , SETTING , AND PARTICIPANTS The Patient-Centered Disease Management ( PCDM ) trial was a multisite r and omized clinical trial comparing a collaborative care PCDM intervention with usual care in patients with HF . A population -based sample of 392 patients with an HF diagnosis from 4 Veterans Affairs centers who had a Kansas City Cardiomyopathy Question naire ( KCCQ ) overall summary score of less than 60 ( heavy symptom burden and impaired functional status and quality of life ) were enrolled between May 2009 and June 2011 . INTERVENTIONS The PCDM intervention included collaborative care by a multidisciplinary care team consisting of a nurse coordinator , cardiologist , psychiatrist , and primary care physician ; home telemonitoring and patient self-management support ; and screening and treatment for comorbid depression . MAIN OUTCOMES AND MEASURES The primary outcome was change in the KCCQ overall summary score at 1 year ( a 5-point change is clinical ly significant ) . Mortality , hospitalization , and depressive symptoms ( Patient Health Question naire 9 ) were secondary outcomes . RESULTS There were no significant differences in baseline characteristics between patients r and omized to the PCDM intervention ( n=187 ) vs usual care ( n=197 ) ; baseline mean KCCQ overall summary scores were 37.9 vs 36.9 ( P=.48 ) . There was significant improvement in the KCCQ overall summary scores in both groups after 1 year ( mean change , 13.5 points in each group ) , with no significant difference between groups ( P=.97 ) . The intervention was not associated with greater improvement in the KCCQ overall summary scores when the effect over time was estimated using 3-month , 6-month , and 12-month data ( P=.74 ) . Among secondary outcomes , there were significantly fewer deaths at 1 year in the intervention arm ( 8 of 187 [ 4.3 % ] ) than in the usual care arm ( 19 of 197 [ 9.6 % ] ) ( P = .04 ) . Among those who screened positive for depression , there was a greater improvement in the Patient Health Question naire 9 scores after 1 year in the intervention arm than in the usual care arm ( 2.1 points lower , P=.01 ) . There was no significant difference in 1-year hospitalization rates between the intervention arm and the usual care arm ( 29.4 % vs 29.9 % , P=.87 ) . CONCLUSIONS AND RELEVANCE This multisite r and omized trial of a multifaceted HF PCDM intervention did not demonstrate improved patient health status compared with usual care . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00461513 Background Heart failure ( HF ) patients discharged from rural hospitals have higher 30-day readmission rates . Self-management ( SM ) reduces readmissions , but adherence to SM guidelines is low in the rural HF population . We tested a home-based intervention to enhance patient activation and lead to improved SM adherence . Methods In this two-group , repeated measures r and omized control trial , the main outcomes were patient reported and clinical outcomes associated with SM adherence , and all-cause readmission at 30 , 90 and 180 days . Results The study included 100 HF patients discharged from a rural critical access hospital . The intervention group received a 12-week SM training and coaching program delivered by telephone and tailored on subjects ’ activation levels . At α = .10 , the PATCH intervention showed significantly greater improvement compared to usual care in patient-reported SM adherence : weighing themselves , following a low-sodium diet , taking prescribed medication , and exercising daily ( all Output:	Statistically significant or positive trends were found in mortality , hospitalization rates , self-care ability , quality of life , anxiety , depression , and sleep , but findings were not robust or consistent .
MS212063	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND There is limited outcome data for super-super-obese ( SSO ) patients , those with Body Mass Index ( BMI ) ≥ 60 kg/m(2 ) , who seek surgical treatment with Laparoscopic Roux-en-Y Gastric Bypass ( LRYGB ) . A large single center LRYGB experience was review ed to compare the safety and efficacy of LRYGB in SSO patients to the st and ard obese population undergoing this procedure . METHODS The American College of Surgeons National Surgical Quality Improvement Program ( ACS NSQIP ) data base and an Institutional Review Board approved prospect i ve data base was used to identify all patients undergoing LRYGB by multiple surgeons at a single institution between 1/1/1994 and 11/15/2013 . Preoperative co-morbidities , postoperative complications , 30-day outcomes , and weight loss at yearly intervals were analyzed to determine difference between SSO patients and NonSSO patients ( BMI < 60 kg/m(2 ) ) . RESULTS Of the 2009 patients undergoing LRYGB over the past 20 years ; 328 had BMI ≥ 60 kg/m(2 ) . Preoperative co-morbidities , conversion to open , and length of stay were significantly increased among SSO patients ; however there was no significant difference in postoperative outcomes or complications . Percent reduction of excess BMI beyond 12 months was significantly improved among NonSSO patients with less than 30 % follow-up beyond 2 years . CONCLUSIONS LRYGB appears well tolerated for super-super-obese patients with BMI ≥ 60 kg/m(2 ) in experienced centers . These patients still have significant reduction in excess BMI despite being less than NonSSO patients undergoing RYGB . The ACS NSQIP data base provides excellent tracking of institutional progress with bariatric surgical outcomes to facilitate the improvement of best practice techniques BACKGROUND Studies have demonstrated that laparoscopic Roux-en-Y gastric bypass ( RYGB ) is associated with the greatest readmission rate among bariatric surgeries . Some readmissions might be avoidable . We sought to evaluate the risk factors for readmission in a high-volume bariatric surgery program at a university hospital in the United States . METHODS We performed a retrospective review of prospect ively maintained data . Patients readmitted within 30 days of laparoscopic RYGB were r and omly matched to control patients who had undergone RYGB in the same year but were not readmitted . The readmissions were categorized as technical complications ( leak ) , wound infections , or malaise ( nausea , dehydration , or benign abdominal pain ) . Patients with a wound infection treated in an outpatient setting were also evaluated and compared with the patients admitted with a wound infection . RESULTS From July 2002 to July 2008 , 450 patients underwent RYGB . Readmission occurred in 42 patients ( 9 % ) . Of these 42 patients , 6 were admitted with wound infections ( 14 % ) , 18 ( 43 % ) with malaise , and 18 ( 43 % ) with technical complications . The patients admitted with wound infections were similar to their controls , except that they were more likely to have publicly funded insurance ( Medicare or Medicaid ) and more likely to present for medical attention to the emergency department after clinic hours . The patients admitted with malaise reported a greater pain score at discharge and were also more likely to have public health insurance than controls . The patients with technical complications did not differ from the control patients in any examined variable . CONCLUSIONS Patients with publicly funded insurance are at increased risk of readmission after RYGB . Outpatient mechanisms for managing wound infections and malaise might result in decreased readmissions Objective : To compare laparoscopic versus open gastric bypass procedures with respect to 30-day morbidity and mortality rates , using multi-institutional , prospect i ve , risk-adjusted data . Summary Background Data : Laparoscopic Roux-en-Y gastric bypass for weight loss is being performed with increasing frequency , partly driven by consumer dem and . However , there are no multi-institutional , risk-adjusted , prospect i ve studies comparing laparoscopic and open gastric bypass outcomes . Methods : A multi-institutional , prospect i ve , risk-adjusted cohort study of patients undergoing laparoscopic and open gastric bypass procedures was performed from hospitals ( n = 15 ) involved in the Private Sector Study of the National Surgical Quality Improvement Program ( NSQIP ) . Data points have been extensively vali date d , are based on st and ardized definitions , and were collected by nurse review ers who are audited for accuracy . Results : From 2000 to 2003 , data from 1356 gastric bypass procedures was collected . The 30-day mortality rate was zero in the laparoscopic group ( n = 401 ) , and 0.6 % in the open group ( n = 955 ) ( P = not significant ) . The 30-day complication rate was significantly lower in the laparoscopic group as compared with the open group : 7 % versus 14.5 % ( P < 0.0001 ) . Multivariate logistic regression analysis was performed to control for potential confounding variables and showed that patients undergoing an open procedure were more likely to develop a complication , as compared with patients undergoing an laparoscopic procedure ( odds ratio = 2.08 ; 95 % confidence interval , 1.33–3.25 ) . Propensity score modeling revealed similar results . A prediction model was derived , and variables that significantly predict higher complication rates after gastric bypass included an open procedure , a high ASA class ( III , IV , V ) , functionally dependent patient , and hypertension as a comorbid illness . Conclusions : Multicenter , prospect i ve , risk-adjusted data show that laparoscopic gastric bypass is safer than open gastric bypass , with respect to 30-day complication rate Objective To compare outcomes , quality of life ( QOL ) , and costs of laparoscopic and open gastric bypass ( GBP ) . Summary Background Data Laparoscopic GBP has been reported to be a safe and effective approach for the treatment of morbid obesity . The authors performed a prospect i ve r and omized trial to compare outcomes , QOL , and costs of laparoscopic GBP with those of open GBP . Methods From May 1999 to March 2001 , 155 patients with a body mass index ( BMI ) of 40 to 60 kg/m2 were r and omly assigned to undergo laparoscopic ( n = 79 ) or open ( n = 76 ) GBP . The two groups were similar in age , sex ratio , mean BMI , and comorbidities . Main outcome measures included operative time , estimated blood loss , length of hospital stay , operative complications , percentage of excess body weight loss , and time to return to activities of daily living and work . Changes in QOL were assessed using the SF-36 Health Survey and the bariatric analysis of reporting outcome system ( BAROS ) . Operative and hospital costs of the two operations were also compared . Results There were no deaths in either group . Mean operative time was longer for laparoscopic GBP than for open GBP , but operative blood loss was less . Two ( 2.5 % ) of the 79 patients in the laparoscopic group required conversion to laparotomy . Median length of hospital stay was shorter for laparoscopic GBP patients ( 3 vs 4 days ) . The rate of postoperative anastomotic leak was similar between groups . Wound-related complications such as infection ( 10.5 vs 1.3 % ) and incisional hernia ( 7.9 vs 0 % ) were more common after open GBP ; late anastomotic stricture was less frequent after open GBP ( 2.6 vs 11.4 % ) . Time to return to activities of daily living and work were shorter after laparoscopic GBP than after open GBP . Weight loss at 1 year was similar between groups . Preoperative SF-36 scores were similar between groups ; however , at 1 month after surgery , laparoscopic patients had better physical conditioning , social functioning , general health , and less body pain than open GBP patients . At 6 months , the BAROS outcome was classified as good or better in 97 % of laparoscopic GBP patients compared with 82 % of open GBP patients . Operative costs were higher for laparoscopic GBP patients , but hospital costs were lower . Conclusions Laparoscopic GBP is a safe and cost-effective alternative to open GBP . Despite a longer operative time , patients undergoing laparoscopic GBP benefited from less blood loss , a shorter hospital stay , and faster convalescence . Laparoscopic GBP patients had comparable weight loss at 1 year but a more rapid improvement in QOL than open GBP patients . The higher initial operative costs for laparoscopic GBP were adequately offset by the lower hospital costs BACKGROUND Our objective was to ascertain procedure-related morbidity among laparoscopic Roux-en-Y gastric bypass ( LRYGB ) , laparoscopic sleeve gastrectomy ( LSG ) , and laparoscopic adjustable gastric b and ing ( LAGB ) patients . These are the 3 most common bariatric procedures performed worldwide . We review ed our experience since the introduction of LSG and compared the procedure-related morbidity among all 3 procedures . STUDY DESIGN We conducted a retrospective review of a prospect ively collected data base of all morbidly obese patients who underwent bariatric surgery between the years 2005 and 2011 . We identified and compared complications , mortality , readmissions , and reoperations in patients who underwent LRYGB , LAGB , and LSG . RESULTS A total of 2,199 bariatric procedures were performed during this period of time . Of those procedures , 1,327 were LRYGB , 619 were LSG , and 253 were LAGB . Perioperative mortality was not applicable for all 3 procedures . The leak rate was 0.5 % for LRYGB and 0.3 % for LSG , and was not applicable for LAGB . The average number of readmissions postoperatively was less than 2 times for all 3 procedures : LRYGB 1.96 times , LSG 1.49 times , and LAGB 1.54 times . The percentages of procedures requiring reoperations due to complications or failures were 14.6 % in the LAGB group , 6.6 % in the LRYGB group , and 1.8 % in the LSG group . CONCLUSIONS In short- and mid-term follow-up , LSG appears to have the lowest procedure-related morbidity when compared with LRYGB and LAGB Output:	They also allow us to evaluate infrequent situations for which r and omized control trials are not feasible and add specific information that can complement the quality of surgical knowledge
MS212064	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: This experimental study examined the effect of communication about type of screening follow-up ( in-person follow-up vs. no in-person follow-up ) on adolescents ' responses to a self-report suicide risk screen . Participants were 245 adolescents ( 131 girls , 114 boys ; ages 13–17 ; 80 % White , 21.6 % Black , 9.8 % American Indian , 2.9 % Asian ) seeking medical emergency services . They were r and omized to a screening follow-up condition . Screening measures assessed primary risk factors for suicidal behavior , including suicidal thoughts , depressive symptoms , alcohol use , and aggressive/delinquent behavior . There was no main effect of follow-up condition on adolescents ' screening scores ; however , significant interactions between follow-up condition and public assistance status were evident . Adolescents whose families received public assistance were less likely to report aggressive-delinquent behavior if assigned to in-person follow-up . Adolescents whose families did not receive public assistance reported significantly higher levels of suicidal ideation if assigned to in-person follow-up . Findings suggest that response biases impact some adolescents ' responses to suicide risk screenings . Because national policy strongly recommends suicide risk screening in emergency setting s , and because screening scores are used to make critical decisions regarding risk management and treatment recommendations , findings indicate the importance of improving the reliability and validity of suicide risk screening for adolescents Objective To assess whether an assertive outreach intervention after suicide attempt could reduce the frequency of subsequent suicidal acts , compared with st and ard treatment . Design R and omised , parallel group , superiority trial with blinded outcome assessment . Setting Outpatient intervention at one location at Copenhagen University Hospital , Denmark . Participants Patients older than 12 years admitted to regional hospitals in Copenhagen with a suicide attempt within the past 14 days . We excluded patients diagnosed with schizophrenia spectrum disorders and patients living in institutions . Intervention Case management through assertive outreach that provided crisis intervention and flexible problem solving . This approach incorporated motivational support and actively assisted patients to scheduled appointments to improve adherence with after-treatment as an add on to st and ard treatment . Main outcome Repeated suicide attempt and death by suicide , recorded in medical records and death register at 1-year follow-up . Results 243 patients were included . During 12 months of follow-up , 20/123 ( 16 % ) patients in the intervention group had been registered in hospital records with subsequent suicide attempt , compared with 13/120 ( 11 % ) in the control group ( odds ratio 1.60 , 95 % confidence interval 0.76 to 3.38 ; P=0.22 ) . By contrast , self reported data on new events showed 11/95 ( 12 % ) in the intervention group versus 13/74 ( 18 % ) in the control group ( 0.61 , 0.26 to 1.46 ; P=0.27 ) . By imputing missing data on the selfreported outcomes , we estimated 15/123 ( 12 % ) events in the intervention group and 23/120 ( 19 % ) in the control group ( 0.69 , 0.34 to 1.43 ; P=0.32 ) . Conclusion Assertive outreach showed no significant effect on subsequent suicide attempt . The difference in rates of events between register data and self reported data could indicate detection bias . Trial registration Clinical Trials.gov NCT00700089 A central component of Dialectical Behavior Therapy ( DBT ) is the teaching of specific behavioral skills with the aim of helping individuals with Borderline Personality Disorder ( BPD ) replace maladaptive behaviors with skillful behavior . Although existing evidence indirectly supports this proposed mechanism of action , no study to date has directly tested it . Therefore , we examined the skills use of 108 women with BPD participating in one of three r and omized control trials throughout one year of treatment and four months of follow-up . Using a hierarchical linear modeling approach we found that although all participants reported using some DBT skills before treatment started , participants treated with DBT reported using three times more skills at the end of treatment than participants treated with a control treatment . Significant mediation effects also indicated that DBT skills use fully mediated the decrease in suicide attempts and depression and the increase in control of anger over time . DBT skills use also partially mediated the decrease of nonsuicidal self-injury over time . Anger suppression and expression were not mediated . This study is the first to clearly support the skills deficit model for BPD by indicating that increasing skills use is a mechanism of change for suicidal behavior , depression , and anger control In a prospect ive-longitudinal study of a representative birth cohort , we tested why stressful experiences lead to depression in some people but not in others . A functional polymorphism in the promoter region of the serotonin transporter ( 5-HT T ) gene was found to moderate the influence of stressful life events on depression . Individuals with one or two copies of the short allele of the 5-HT T promoter polymorphism exhibited more depressive symptoms , diagnosable depression , and suicidality in relation to stressful life events than individuals homozygous for the long allele . This epidemiological study thus provides evidence of a gene-by-environment interaction , in which an individual 's response to environmental insults is moderated by his or her genetic makeup Background There have been only a few reports illustrating the moderate effectiveness of suicide-preventive interventions in reducing suicidal behavior , and , in most of those studies , the target population s were primarily adults , whereas few focused on adolescents . Essentially , there have been no r and omized controlled studies comparing the efficacy , cost-effectiveness and cultural adaptability of suicide-prevention strategies in schools . There is also a lack of information on whether suicide-preventive interventions can , in addition to preventing suicide , reduce risk behaviors and promote healthier ones as well as improve young people 's mental health . The aim of the SEYLE project , which is funded by the European Union under the Seventh Framework Health Program , is to address these issues by collecting baseline and follow-up data on health and well-being among European adolescents and compiling an epidemiological data base ; testing , in a r and omized controlled trial , three different suicide-preventive interventions ; evaluating the outcome of each intervention in comparison with a control group from a multidisciplinary perspective ; as well as recommending culturally adjusted models for promoting mental health and preventing suicidal behaviors . Methods and design The study comprises 11,000 adolescents emitted from r and omized schools in 11 European countries : Austria , Estonia , France , Germany , Hungary , Irel and , Israel , Italy , Romania , Slovenia and Spain , with Sweden serving as the scientific coordinating center . Each country performs three active interventions and one minimal intervention as a control group . The active interventions include gatekeeper training ( QPR ) , awareness training on mental health promotion for adolescents , and screening for at-risk adolescents by health professionals . Structured question naires are utilized at baseline , 3- and 12-month follow-ups in order to assess changes . Discussion Although it has been reported that suicide-preventive interventions can be effective in decreasing suicidal behavior , well-documented and r and omized studies are lacking . The effects of such interventions in terms of combating unhealthy lifestyles in young people , which often characterize suicidal individuals , have never been reported . We know that unhealthy and risk-taking behaviors are detrimental to individuals ' current and future health . It is , therefore , crucial to test well- design ed , longitudinal mental health-promoting and suicide-preventive interventions by evaluating the implication s of such activities for reducing unhealthy and risk behaviors while concurrently promoting healthy ones . Trial registration The German Clinical Trials Register , DRKS00000214 OBJECTIVE To determine whether brief intervention and contact is effective in reducing subsequent suicide mortality among suicide attempters in low and middle-income countries . METHODS Suicide attempters ( n = 1867 ) identified by medical staff in the emergency units of eight collaborating hospitals in five culturally different sites ( Campinas , Brazil ; Chennai , India ; Colombo , Sri Lanka ; Karaj , Islamic Republic of Iran ; and Yuncheng , China ) participated , from January 2002 to October 2005 , in a r and omized controlled trial to receive either treatment as usual , or treatment as usual plus brief intervention and contact ( BIC ) , which included patient education and follow-up . Overall , 91 % completed the study . The primary study outcome measurement was death from suicide at 18-month follow-up . FINDINGS Significantly fewer deaths from suicide occurred in the BIC than in the treatment-as-usual group ( 0.2 % versus 2.2 % , respectively ; chi2 = 13.83 , P < 0.001 ) . CONCLUSION This low-cost brief intervention may be an important part of suicide prevention programmes for underre source d low- and middle-income countries CONTEXT Universal screening for mental health problems and suicide risk is at the forefront of the national agenda for youth suicide prevention , yet no study has directly addressed the potential harm of suicide screening . OBJECTIVE To examine whether asking about suicidal ideation or behavior during a screening program creates distress or increases suicidal ideation among high school students generally or among high-risk students reporting depressive symptoms , substance use problems , or suicide attempts . DESIGN , SETTING , AND PARTICIPANTS A r and omized controlled study conducted within the context of a 2-day screening strategy . Participants were 2342 students in 6 high schools in New York State in 2002 - 2004 . Classes were r and omized to an experimental group ( n = 1172 ) , which received the first survey with suicide questions , or to a control group ( n = 1170 ) , which did not receive suicide questions . MAIN OUTCOME MEASURES Distress measured at the end of the first survey and at the beginning of the second survey 2 days after the first measured on the Profile of Mood States adolescent version ( POMS-A ) instrument . Suicidal ideation assessed in the second survey . RESULTS Experimental and control groups did not differ on distress levels immediately after the first survey ( mean [ SD ] POMS-A score , 5.5 [ 9.7 ] in the experimental group and 5.1 [ 10.0 ] in the control group ; P = .66 ) or 2 days later ( mean [ SD ] POMS-A score , 4.3 [ 9.0 ] in the experimental group and 3.9 [ 9.4 ] in the control group ; P = .41 ) , nor did rates of depressive feelings differ ( 13.3 % and 11.0 % , respectively ; P = .19 ) . Students exposed to suicide questions were no more likely to report suicidal ideation after the survey than unexposed students ( 4.7 % and 3.9 % , respectively ; P = .49 ) . High-risk students ( defined as those with depression symptoms , substance use problems , or any previous suicide attempt ) in the experimental group were neither more suicidal nor distressed than high-risk youth in the control group ; on the contrary , depressed students and previous suicide attempters in the experimental group appeared less distressed ( P = .01 ) and suicidal ( P = .02 ) , respectively , than high-risk control students . CONCLUSIONS No evidence of iatrogenic effects of suicide screening emerged . Screening in high schools is a safe component of youth suicide prevention efforts The purpose of this study was to examine the efficacy of the Youth-Nominated Support Team-Version II ( YST-II ) for suicidal adolescents , an intervention based on social support and health behavior models , which was design ed to supplement st and ard treatments . Psychiatrically hospitalized and suicidal adolescents , 13 - 17 years of age , were r and omly assigned to treatment-as-usual ( TAU ) + YST-II ( n = 223 ) or TAU only ( n = 225 ) . YST-II provided tailored psychoeducation to youth-nominated adults in addition to weekly check-ins for 3 months following hospitalization . In turn , these adults had regular supportive contact with adolescents . Adolescents assigned to TAU + YST-II had an average of 3.43 ( SD = 0.83 ) nominated adults . Measures included the Suicidal Ideation Question naire-Junior ( SIQ-JR ; W. M. Reynolds , 1988 ) , Children 's Depression Rating Scale-Revised ( E. O. Poznanski & H. B. Mokros , 1996 ) , Beck Hopelessness Scale ( A. T. Beck & R. A. Steer , 1993 ) , and Child and Adolescent Functional Assessment Scale ( CAFAS ; K. Hodges , 1996 ) . YST-II had very limited positive effects , which were moderated by history of multiple suicide attempts , and no negative effects . It result ed in more rapid decreases in suicidal ideation ( SIQ-JR ) for multiple suicide attempters during the initial 6 weeks after hospitalization ( small-to-moderate effect size ) . For nonmultiple attempters , it was associated with greater declines in functional impairment ( CAFAS ) at 3 and 12 months ( small effect sizes ) . YST-II had no effects on suicide attempts and no enduring effects on SIQ-JR scores AIM Suicide attempt , ideation and deliberate self-harm are common among adolescents . Limited evidence exists regarding interventions that can reduce risk ; however , research indicates that maintaining contact with at-risk adults following discharge from services via letter or postcard can reduce risk . The aim of the study was to test a postcard intervention among people aged 15 - 24 who presented to mental health services but were not accepted , yet were at risk of suicide . METHODS A r and omized controlled trial Output:	The anti-suicidal effects of clozapine and lithium have been substantiated , but might be less specific than previously thought . Insufficient evidence exists to assess the possible benefits for suicide prevention of screening in primary care , in general public education and media guidelines .
MS212065	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: & NA ; To increase cardiopulmonary arrest survival , the American Heart Association developed basic and advanced cardiac life support ( ACLS ) courses that expose participants to realistic learning situations . This experimental study compared results of two ACLS classes on measures of knowledge ( content exam ) and resuscitation skills ( performance exam ) . Both the control and experimental groups consisted of physicians , nurses , emergency medical technicians , respiratory therapists , and advanced health care providers . The control group used low‐fidelity simulation ( LFS ) ; the experimental group was exposed to enhanced realism via high‐fidelity simulation ( HFS ) . The findings showed a positive correlation between enhanced practice and learning but no significant correlation between posttest and skills test scores for the LFS and HFS groups . The HFS group did score higher on both cognitive and behavioral tests , but the difference was not statistically significant . Participants from both groups indicated satisfaction with their forms of simulation experience and course design . In addition , participants ' self‐confidence to care for a victim of cardiopulmonary arrest was increased after completing their course ; profession and work experience had no effect on responses . The largest difference noted was in verbal responses to course satisfaction . The experimental group stated that learning using HFS was enjoyable and adamantly recommended that ACLS should only be taught using HFS . Further study is required to assess if practicing beyond the course enhances short‐ and long‐term retention of ACLS techniques Objectives : To assess the effect of high-fidelity simulation ( SIM ) on cognitive performance after a training session involving several mock resuscitations design ed to teach and reinforce Pediatric Advanced Life Support ( PALS ) algorithms . Methods : Pediatric residents were r and omized to high-fidelity simulation ( SIM ) or st and ard mannequin ( MAN ) groups . Each subject completed 3 study phases : ( 1 ) mock code exercises ( asystole , tachydysrhythmia , respiratory arrest , and shock ) to assess baseline performance ( PRE phase ) , ( 2 ) a didactic session review ing PALS algorithms , and ( 3 ) repeated mock code exercises requiring identical cognitive skills in a different clinical context to assess change in performance ( POST phase ) . SIM subjects completed all 3 phases using a high-fidelity simulator ( SimBaby , Laerdal Medical , Stavanger , Norway ) , and MAN subjects used SimBaby without simulated physical findings ( ie , as a st and ard mannequin ) . Performance in PRE and POST was measured by a scoring instrument design ed to measure cognitive performance ; scores were scaled to a range of 0 to 100 points . Improvement in performance from PRE to POST phases was evaluated by mixed modeling using a r and om intercept to account for within-subject variability . Results : Fifty-one subjects ( SIM , 25 ; MAN , 26 ) completed all phases . The PRE performance was similar between groups . Both groups demonstrated improvement in POST performance . The improvement in scores between PRE and POST phases was significantly better in the SIM group ( mean [ SD ] , 11.1 [ 4.8 ] vs. 4.8 [ 1.7 ] , P = 0.007 ) . Conclusions : The use of high-fidelity simulation in a PALS training session result ed in improved cognitive performance by pediatric house staff . Future studies should address skill and knowledge decays and team dynamics , and clearly defined and reproducible outcome measures should be sought OBJECTIVE To assess the educational efficacy of a Web-based pediatric advanced life support course ( Web-PALS ) . DESIGN Nonr and omized , prospect i ve , cohort study . SETTING University medical center . PARTICIPANTS Health care providers ( includes physicians , nurses , paramedics , and respiratory therapists ) taking either the Web-PALS or a traditional PALS course ( Trad-PALS ) . MAIN EXPOSURE Web-PALS . MAIN OUTCOME MEASURES Postcourse written examination scores and scored videotapes of students performing 5 PALS procedures were compared between study groups . Students completed precourse and postcourse question naires , rating on a 5-point Likert scale their self-confidence to perform PALS assessment s and procedures . A structured , course satisfaction survey was given after students had taken the Web-PALS course . RESULTS Eighty-six students completed the study ( 44 Web-PALS and 42 Trad-PALS ) . All students achieved a passing score on the written examination on their first attempt . Compared with students in the Trad-PALS group , students in the Web-PALS group scored slightly lower ( 97.1 % vs 95.4 % ; difference , 1.7 % ; 95 % confidence interval , 0.1 - 3.2 ) . Mean overall videotape scores were similar among the Web-PALS and Trad-PALS groups ( 75.0 % vs 73.0 % ; difference , 2.0 % ; 95 % confidence interval , -2.0 to 6.0 ) . After completing the Web-PALS course , the mean level of confidence improved from 3.77 to 4.28 ( difference , 0.51 ; 95 % confidence interval , 0.33 - 0.69 ) . Ninety-six percent of respondents indicated that Web-PALS met all of the stated objectives of the PALS course . All respondents indicated that they would recommend Web-PALS to a colleague . CONCLUSIONS Students perceive Web-PALS as a positive educational experience . Though not identical to students taking the Trad-PALS course , they performed well on postcourse cognitive and psychomotor testing . These findings support Web-PALS as an acceptable format for administering the PALS course Objective This feasibility study aim ed to describe and evaluate the effectiveness of a novel chest re-opening paediatric resuscitation scenario training scheme . Methods A novel scheme offering training on specialist skills required for post-operative cardiac patients such as chest re-opening and cardiac pacing via simulation was described . A prospect i ve audit of the first 23 consecutive training sessions was conducted to assess the scheme ’s effectiveness . Parameters assessed included timing of chest re-opening or cardiac pacing orders , and any delays in carrying out these orders . Results The median time required for the medical team leader to order chest re-opening was 4 min . New medical leaders took significantly longer to order chest re-opening than experienced medical team leaders ( P = 0.02 , Mann – Whitney U test ) . The performance of the team-in-training deteriorated with the introduction of new members but was correctable with serial training . Conclusions Effective simulation training integrating chest re-opening and cardiac pacing into st and ard paediatric resuscitation guidelines may be achieved without high fidelity simulation equipment One hundred thirty-two physicians who successfully completed advanced cardiac life support ( ACLS ) training were r and omly placed in a control group or one of two groups receiving interventions design ed to provide reinforcement of previously mastered knowledge and skills . These interventions included mailed periodic reprints ( group 1 ) or quarterly patient management problems ( group 2 ) . All physicians were retested for knowledge and skills related to ACLS one year later . Fifty-two ( 39.4 % ) could successfully ventilate the mannequin , and 62 ( 47.0 % ) could perform cardiac compression adequately . No differences were noted among groups . Significant differences in knowledge were found . The control group initiated appropriate therapy in a mock-arrest situation 52 % of the time , while group 1 averaged 75 % and group 2 averaged 82 % . These results indicate that reinforcement after continuing medical education may enhance knowledge retention , but does not maintain motor skills . Yearly recertification in ACLS skills should be considered , and frequent practice sessions should be encouraged for those physicians who are not active participants in ACLS activities INTRODUCTION The CAREvent Public Access Resuscitator ( PAR , O-Two Medical Technologies , Ontario , Canada ) is a new oxygen-driven device alternating two ventilations with 15 prompts for chest compressions . The PAR is design ed for use with a st and ard resuscitation face mask and is equipped with mask leakage and obstruction alarms . The purpose of this study was to assess the quality of basic life support ( BLS ) by hospital nurses and to evaluate if BLS with the PAR is better than BLS using the mouth-to-mask technique . METHODS The study group consisted of 352 nurses from Ghent University Hospital working outside the critical care and emergency departments . BLS skills were measured using a Laerdal Skillreporter manikin ( Laerdal , Norway ) connected to a Laerdal PC Skillreporting system . To assess base line skills , 200 nurses were tested without previous notice in single rescuer BLS using a pocket mask ( PM , Laerdal , Norway ) or a bag-valve mask device ( Laerdal , Norway ) over a period of 2 min . A separate consecutive sample of 152 nurses was r and omised to the PM or PAR groups after a st and ard BLS refresher course . The PAR group received a short period of training in PAR use . Immediately after training , both groups performed the 2 min single rescuer BLS test . RESULTS Unprepared nurses achieved only 26 compressions and 3 ventilations/min . Immediately after training , nurses using the PAR delivered 54 compressions/min as opposed to 35 for the PM group ( p<0.0001 ) . PAR users ventilated six times/min compared to five times for PM users ( p<0.0001 ) . CONCLUSION Immediately after training , the use of the PAR improved BLS performance by ward nurses significantly , bringing the number of ventilations and compressions per minute close to the theoretical maximum achievable within the current guidelines . Retention tests after 6 and 12 months will show if the effect is sustained Problem : Advance cardiac life support ( ACLS ) training does not address coordination of team re sources to improve the ability of teams to deliver needed treatments reliably and rapidly . Our objective was to use a human simulation training educational environment to develop multidisciplinary team skills and improve medical emergency team ( MET ) performance . We report findings of a crisis team training course that is focused on organization . Setting : Large center for human simulation training at a university affiliated tertiary care hospital . Participants : Ten courses were delivered and 138 clinical ly experienced individuals were trained ( 69 critical care nurses , 48 physicians , and 21 respiratory therapists ) . All participants were ACLS trained and experienced in responding to cardiac arrest situations . Course design : Each course had four components : ( 1 ) a web based presentation and pretest before the course ; ( 2 ) a brief reinforcing didactic session on the day of the course ; ( 3 ) three of five different simulated scenarios ; each followed by ( 4 ) debriefing and analysis with the team . Three of five simulator scenarios were used ; scenario selection and order was r and om . Trainees did not repeat any scenario or role during the training . Participants were video recorded to assist debriefing . Debriefing focused on reinforcing organizational aspects of team performance : assuming design ated roles independently , completing goals ( tasks ) assigned to each role , and directed communication . Measures for improvement : Participants grade d their performance of specific organizational and treatment tasks within specified time intervals by consensus . Simulator “ survival ” depended on supporting oxygenation , ventilation , circulation within 60 seconds , and delivering the definitive treatment within 3 minutes . Effects of change : Simulated survival ( following predetermined criteria for death ) increased from 0 % to 89 % . The initial team task completion rate was 10–45 % and rose to 80–95 % during the third session . Lessons learnt : Training multidisciplinary teams to organize using simulation technology is feasible . This preliminary report warrants more detailed inquiry BACKGROUND Critical pediatric illness or injury occurs infrequently in out-of-hospital setting s , making it difficult for paramedics to maintain physical assessment , treatment , and procedure skills . OBJECTIVES To document the ability of paramedics to retain clinical knowledge over a one-year interval after completing a pediatric resuscitation course and to determine whether clinical experience or retesting improves retention . METHODS This was a r and omized controlled study assessing retention of knowledge in pediatric resuscitation soon after , six months after , and 12 months following completion of a pediatric advanced life support course . Forty-three paramedics participated in pre- and post-pediatric resuscitation course testing and were r and omly assigned to one of four groups . Group 1 received a knowledge examination ( KE ) and mock resuscitation scenarios ( MR ) at six months . Group 2 received only the KE at six months . Group 3 received the MR only at six months . Group 4 received no intermediate testing . All groups were reassessed at 12 months . RESULTS Pediatric clinical knowledge ( as measured by KE ) rose sharply immediately after the course but returned to baseline levels within six months . There was no difference between the groups in knowledge scores at 12 months , despite the interventions at six months . CONCLUSIONS Although intensive out-of-hospital pediatric education enhances knowledge , that knowledge rapidly decays . Emergency medical services programs need to find novel ways to increase retention and ensure paramedic readiness OBJECTIVE To evaluate the effectiveness of an educational intervention on pediatric residents ' resuscitation fund of knowledge , technical skills , confidence , and overall performance . DESIGN Prospect i ve , nonconcurrent , controlled interventional trial . SETTING Urban pediatric tertiary care hospital . PARTICIPANTS An intervention group ( IG ) of 28 pediatric residents graduating in 1997 , and a control group ( CG ) of 30 pediatric residents graduating in 1996 . INTERVENTIONS Resuscitation course with didactic lectures and skills practice stations , as well as a minimum of 3 practice mock resuscitations with immediate feedback throughout postgraduate year 3 . MAIN OUTCOME MEASURES Fund of knowledge , using the Pediatric Advanced Life Support test and short answer test ; technical skills , using the Airway and Vascular Access Skills Assessment ; experience and confidence , using an anonymous survey ; and overall performance , evaluated using a videotaped mock resuscitation test . RESULTS The IG scored better on the Output:	Findings of the review were : SRTs result in an improvement in knowledge and skills in those who attend them , deterioration in skills and , to a lesser extent , knowledge is highly likely as early as three months following SRTs , booster or refresher sessions may improve an individual 's ability to retain resuscitation skills after initial training and the instigation of resuscitation training in a healthcare institution significantly improves clinical management of resuscitations and patient outcome ( including survival ) after resuscitation attempts
MS212066	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND The Intercontinental Schizophrenia Outpatient Health Outcomes ( IC-SOHO ) study was design ed to provide information regarding use and outcome of antipsychotic treatments in a large , diverse population in real practice setting s. METHOD Out patients with schizophrenia ( ICD-10 or DSM-IV ) who initiated or changed to a new antipsychotic entered this 3-year , naturalistic , prospect i ve observational study . Four monotherapy treatment groups were defined according to the antipsychotic prescribed at baseline , namely olanzapine , risperidone , quetiapine , and haloperidol . Efficacy was assessed using the Clinical Global Impressions-Severity of Illness rating scale ( CGI-S ) , inclusive of subscales for positive , negative , depressive , and cognitive symptoms . Tolerability was assessed by adverse event question naires and weight measurements . Six-month findings are described . RESULTS At baseline , 5833 participants were prescribed monotherapy and the mean severity of illness was moderate to marked ( CGI-S ) . At 6 months , olanzapine result ed in significantly greater improvements in overall , positive , negative , depressive , and cognitive symptoms compared with quetiapine , risperidone or haloperidol ( p < .001 ) . Improvements in overall , negative , and cognitive symptoms were significantly higher for risperidone compared with haloperidol ( p < .001 ) , whereas improvements across all symptoms were comparable for quetiapine and haloperidol . Extra-pyramidal symptoms and tardive dyskinesia decreased compared with baseline in the olanzapine , quetiapine , and risperidone groups but increased in the haloperidol group ( p < .001 , likelihood of extrapyramidal symptoms with haloperidol compared with olanzapine , quetiapine , or risperidone ) . Sexual function adverse events were most prominent in the haloperidol and risperidone treatment groups . Weight change was significantly greater for olanzapine compared with the other antipsychotics ( p < .001 ) . CONCLUSION Our results support the previously reported positive impact of atypical antipsychotics , particularly olanzapine , in patients with schizophrenia To evaluate the maintenance of efficacy of risperidone long‐acting injectable ( RLAI ) in stable patients with schizophrenia or schizoaffective disorders . The prevalence of patients who met st and ardized remission criteria will be also evaluated as well as the predictors factors of remission according to psychopathological , psychosocial and subjective correlates OBJECTIVE Despite the frequent use of the Positive and Negative Syndrome Scale ( PANSS ) for rating the symptoms of schizophrenia , the clinical meaning of its total score and of the cut-offs that are used to define treatment response ( e.g. at least 20 % or 50 % reduction of the baseline score ) are as yet unclear . We therefore compared the PANSS with simultaneous ratings of Clinical Global Impressions ( CGI ) . METHOD PANSS and CGI ratings at baseline ( n = 4091 ) , and after one , two , four and six weeks of treatment taken from a pooled data base of seven pivotal , multi-center antipsychotic drug trials on olanzapine or amisulpride in patients with exacerbations of schizophrenia were compared using equipercentile linking . RESULTS Being considered " mildly ill " according to the CGI approximately corresponded to a PANSS total score of 58 , " moderately ill " to a PANSS of 75 , " markedly ill " to a PANSS of 95 and severely ill to a PANSS of 116 . To be " minimally improved " according to the CGI score was associated with a mean percentage PANSS reduction of 19 % , 23 % , 26 % and 28 % at weeks 1 , 2 , 4 and 6 , respectively . The corresponding figures for a CGI rating " much improved " were 40 % , 45 % , 51 % and 53 % . CONCLUSIONS The results provide a better framework for underst and ing the clinical meaning of the PANSS total score in drug trials of schizophrenia patients with acute exacerbations . Such studies may ideally use at least a 50 % reduction from baseline cut-off to define response rather than lower thresholds . In treatment resistant population s , however , even a small improvement can be important , so that a 25 % cut-off might be appropriate Background Because wide variations in mental health care utilization exist throughout the world , determining long-term effectiveness of psychotropic medications in a real-world setting would be beneficial to physicians and patients . The purpose of this analysis was to describe the effectiveness of injectable risperidone long-acting therapy ( RLAT ) for schizophrenia across countries . Methods This was a pragmatic analysis of data from two prospect i ve observational studies conducted in the US ( Schizophrenia Outcomes Utilization Relapse and Clinical Evaluation [ SOURCE ] ; Clinical Trials.gov registration number for the SOURCE study : NCT00246194 ) and Spain , Australia , and Belgium ( electronic Schizophrenia Treatment Adherence Registry [ eSTAR ] ) . Two separate analyses were performed to assess clinical improvement during the study and estimate psychiatric hospitalization rates before and after RLAT initiation . Clinical improvement was evaluated using the Clinical Global Impressions-Severity ( CGI-S ) and Global Assessment of Functioning ( GAF ) scales , and change from baseline was evaluated using paired t tests . Psychiatric hospitalization rates were analyzed using incidence densities , and the bootstrap resampling method was used to examine differences between the pre-baseline and post-baseline periods . Results The initial sample comprised 3,069 patients ( US , n = 532 ; Spain , n = 1,345 ; Australia , n = 784 ; and Belgium , n = 408 ) . In all , 24 months of study participation , completed by 39.3 % ( n = 209 ) , 62.7 % ( n = 843 ) , 45.8 % ( n = 359 ) , and 64.2 % ( n = 262 ) of patients from the US , Spain , Australia , and Belgium , respectively , were included in the clinical analysis . Improvements compared with baseline were observed on both clinical assessment s across countries ( P < 0.001 at all post-baseline visits ) . The mean improvement was approximately 1 point on the CGI-S and 15 points on the GAF . A total of 435 ( 81.8 % ) , 1,339 ( 99.6 % ) , 734 ( 93.6 % ) , and 393 ( 96.3 % ) patients from the US , Spain , Australia , and Belgium , respectively , had ≥1 post-baseline visit and were included in the analysis of psychiatric hospitalization rates . Hospitalization rates decreased significantly in all countries regardless of hospitalization status at RLAT initiation ( P < 0.0001 ) and decreased significantly in the US and Spain ( P < 0.0001 ) when the analysis was limited to out patients only . Conclusions RLAT in patients with schizophrenia was associated with improvements in clinical and functional outcomes and decreased hospitalization rates in the US , Spain , Australia , and Belgium , despite differences in health care delivery systems OBJECTIVE Adding another antipsychotic to a treatment regimen was previously used in evaluating the medication 's efficacy . Supplementation of depot antipsychotics with oral antipsychotics is particularly meaningful because depot formulations are typically chosen for patients struggling with adherence to oral antipsychotics . This post-hoc analysis assessed supplementation of olanzapine long-acting injection ( olanzapine-LAI ) with oral olanzapine . SUBJECTS AND METHODS We used 12 months of data from an open-label , single-arm extension study of patients with schizophrenia or schizoaffective disorder ( N=931 ) treated with olanzapine-LAI . The prevalence , duration , time to first supplementation , and best predictors of oral supplementation were assessed . RESULTS Oral supplementation occurred in 21 % of patients for a median of 31 days with mean modal dose of 10.8 mg/day . Mean time to first supplementation was shorter for patients who were at least moderately ill at baseline compared to less ill patients ( 47 vs. 97 days , p<0.001 ) . Best predictors of oral supplementation included a more severe illness profile at baseline , lower olanzapine-LAI dose prior to oral supplementation , supervised living arrangements , and being African-American . CONCLUSION Supplementation of olanzapine-LAI appears to be infrequent , of relatively short duration , and reserved for more severely ill patients who may require a targeted rescue medication due to signs of impending relapse This study assessed the efficacy and the safety of a dosing regimen that was revised from earlier studies for the investigational injectable atypical antipsychotic paliperidone palmitate ( approved in the USA , August 2009 ) for adult patients with acutely exacerbated schizophrenia . The patients ( N = 652 ) were r and omly assigned ( 1:1:1:1 ) to paliperidone palmitate at 25 , 100 , or 150 mg eq. or placebo in this 13-week double-blind study . The patients received an injection of paliperidone palmitate at 150 mg eq. or placebo in the deltoid muscle on day 1 and the assigned fixed dose or placebo in the deltoid or muscle on day 8 and then once monthly ( days 36 and 64 ) . No oral supplementation was used . Target plasma levels were achieved by day 8 in all paliperidone palmitate groups . The mean change in Positive and Negative Syndrome Scale total score from baseline to end point improved significantly ( P ≤ 0.034 ) in all the paliperidone palmitate dose-groups versus placebo . Paliperidone palmitate treatment with this revised dosing regimen led to the achievement of rapid and consistent therapeutically effective plasma levels that were maintained by once-monthly dosing in either the deltoid or gluteal muscle . Common treatment-emergent adverse events ( ≥2 % of patients in any of the treatment groups ) that occurred more frequently in the total paliperidone palmitate group versus the placebo group ( with ≥1 % difference ) were injection-site pain ( 7.6 % vs 3.7 % ) , dizziness ( 2.5 % vs 1.2 % ) , sedation ( 2.3 % vs 0.6 % ) , pain in the extremity ( 1.6 % vs 0.0 % ) , and myalgia ( 1.0 % vs 0.0 % ) . The paliperidone palmitate treatment was efficacious and generally tolerated across the dose range ( 25 , 100 , or 150 mg eq. ) in adult patients with acutely exacerbated schizophrenia . Abbreviations : BMI - body mass index , CGI-S - Clinical Global Impression-Severity , EPS - extrapyramidal symptoms , ER - extended release , ITT - intent-to-treat , LAI - long-acting injectable , PANSS - Positive and Negative Syndrome Scale , PK - pharmacokinetic , PSP - Personal and Social Performance Scale , TEAE - treatment-emergent adverse events , VAS - Visual Analogue OBJECTIVE The authors assessed the efficacy and safety of the first long-acting atypical antipsychotic ( long-acting injectable risperidone ) in patients with schizophrenia . METHOD In a 12-week , multicenter , double-blind , r and omized study , patients received intramuscular injections every 2 weeks of placebo or long-acting risperidone ( 25 mg , 50 mg , or 75 mg ) . The primary measure of efficacy was the change in total score on the Positive and Negative Syndrome Scale . RESULTS Of the 554 patients who were enrolled , 400 entered the double-blind study , and 370 received at least one postbaseline assessment . Mean changes in score of -6.2 , -8.5 , and -7.4 on the Positive and Negative Syndrome Scale were seen at endpoint for the 25- , 50- , and 75-mg risperidone groups , respectively ; all three change scores were significantly different from that seen with placebo ( + 2.6 ) . Improvements in positive and negative symptoms were also significantly greater in patients receiving risperidone . Long-acting risperidone was well tolerated . Adverse events related to extrapyramidal symptoms were spontaneously reported by 13 % of patients receiving placebo and 10 % of patients in the 25-mg risperidone group , with higher rates in the 50-mg and 75-mg groups . Severity of extrapyramidal symptoms was mild at baseline and throughout the trial in each treatment group . Mean weight changes were small in the 25- , 50- , and 75-mg risperidone groups ( 0.5 kg , 1.2 kg , and 1.9 kg , respectively ) . Injection site pain was rated as low by the patients , consistent with the investigators ' pain ratings . CONCLUSIONS Long-acting injectable risperidone was efficacious and well tolerated and provides both clinicians and patients with a new mode of treatment that can improve the outcome of long-term therapy Abstract Objective To study the association between prescribed antipsychotic drugs and outcome in schizophrenia or schizoaffective disorder in the community . Design Prospect i ve cohort study using national central registers . Setting Community care in Finl and . Participants Nation Output:	Conclusion Using treatment-completion rates as a proxy measure of medication effectiveness , olanzapine long-acting injection did not differ significantly from risperidone long-acting injection when including all eligible studies .
MS212067	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Aim : To evaluate and compare the pH and antibacterial property of Ca(OH)2 combined with iodine potassium iodide ( IKI ) or chlorhexidine ( CHX ) on E. faecalis and to assess and compare their effect on fracture resistance of root dentin . Material s and Methods : CHX ( 0.5 % ) The following test material s were used : Group I Calcium hydroxide + saline , Group II Calcium hydroxide + CHX ( 0.5 % ) and Group III Calcium hydroxide + IKI ( 2 % ) . For antibacterial activity , 60 root dentin blocks ( 20 in each group ) were infected by E. faecalis followed by placement of medicaments . At the end of 24 h and 7 days , 10 sample s from each group were r and omly chosen and assessed for antibacterial activity . For evaluation of root strength , 30 teeth were used and stored in sterile saline after placement of medicament . At the end of 30 days , sample s were subjected to fracture resistance testing on the Universal Strength Testing Machine . Hounsfield strength testing machine , UK pH of the various calcium hydroxide combinations was determined with a digital pH meter . Statistical analysis : Kruskal Wallis test , Mann Whitney U test , and one-way ANOVA test for intergroup comparison and Wilcoxon 's signed rank test and student 's paired t test for intragroup comparison . Results : Group III showed significantly greater antibacterial activity against E. faecalis , followed by group II and control group . There was no statistically significant change in the pH and root strength values among all the groups . Conclusion : The present study revealed that IKI or CHX in combination with Ca(OH)2 is an effective medicament against E. faecalis Contamination of the root canal system by persistent , enteric bacteria via leakage through interim restorations has been well documented . This in vitro study evaluated the ability of interappointment medications to prevent contamination of the root canal system by Enterococcus faecalis . Coronally unsealed , medicated tooth roots fixed in a closed system were contaminated daily with a st and ardized , aerobic , broth culture of E. faecalis . Four medications were evaluated ( n = 15 ) : group A , calcium hydroxide/methylcellulose paste ; group B , camphorated parachlorophenol/calcium hydroxide paste ; group C , 1 % chlorhexidine/methylcellulose gel ; and group D , calcium hydroxide points . The mean number of days to contamination as indicated by turbidity in the closed system was the following : group A , 37 ; group B , 46 ; group C , 16 ; group D , 5 ; and a positive control ( no medication ) , 3 . A one-way analysis of variance with a Scheffe post hoc test ( p = 0.05 ) detected significant differences in effectiveness with A and B superior to C and D , and C superior to OBJECTIVE The aim of this in vitro study was to assess the substantive antimicrobial activity of different medicaments in human root dentin . STUDY DESIGN Canals of 98 roots were enlarged to st and ard size and medicated for 7 days with the following : ( 1 ) 2 % chlorhexidine ( CHX ) gel , ( 2 ) 0.2 % CHX gel , ( 3 ) 2 % CHX solution , ( 4 ) Ca(OH)(2 ) , ( 5 ) Ca(OH)(2)+ 0.2 % CHX gel , ( 6 ) 2 % CHX solution + a 25 % CHX-containing controlled-release device , ( 7 ) saline , and ( 8) gel vehicle . After medication , canals were inoculated with Enterococcus faecalis for 21 days . Dentin sample s were collected with Gates-Glidden burs into brain heart infusion broth , and bacterial growth was assessed with spectrophotometric analysis of optical density after 72 hours of incubation . RESULTS Mean optical densities were significantly lower for groups with 2 % CHX ( 1 , 3 , and 6 ) when compared with those of the controls ( P < .05 , analysis of variance with the Tukey test ) . Other groups did not differ significantly from the controls . CONCLUSIONS Canal dressing for 1 week with 2 % CHX may provide residual antimicrobial activity against E faecalis Previous studies have demonstrated antimicrobial substantivity in root canal dentin up to 7 days after treatment with chlorhexidine . This in vitro study assessed the antimicrobial substantivity of chlorhexidine-treated bovine root dentin over a period of 21 days . Sixty st and ardized bovine root sections were r and omly divided into three equal groups , and their canals immersed in one of the following solutions : ( i ) sterile saline ; ( ii ) 2.5 % NaOCl ; or ( iii ) 0.2 % chlorhexidine ( CHX ) . Half the specimens in each group were treated with the solution for 5 min and the other half for 7 days . After solutions were removed , the specimens were incubated at 37 degrees C in Brain Heart Infusion broth containing Enterococcus faecalis ( ATCC 29212 ) . A fresh inoculum was added to the broth every other day over a 21-day period . The canals were then enlarged with sterile burs , and the dentin shavings collected and cultured for the presence of cultivable bacteria in the dentinal tubules . Specimens treated with CHX for 7 days demonstrated significantly less dentin colonization by E. faecalis than the other specimens . CHX has potential as an intracanal medicament , if it can be applied for a period of at least 7 days AIM To determine the viability of Enterococcus faecalis in infected human root dentine in vitro after exposure to root canal medicaments based on chlorhexidine and octenidine . METHODOLOGY Human root segments ( n = 40 ) were infected with E. faecalis for 8 weeks . Root dentine sample s ( rd ) collected at week 4 served as individual baseline values . At week 8 , the root segments were r and omly divided into four test groups ( n = 10 each ) for the placement of one of the following medicaments in the root canals : calcium hydroxide paste ( CH ) , chlorhexidine gel ( CHX-gel ) ( 5.0 % ) , chlorhexidine/gutta-percha points ( CHX-GP ) ( active points ( ® ) ; Roeko , Langenau , Germany ) and octenidine gel ( OCT-gel ) ( 5.0 % ) followed by incubation for 4 weeks . The effect on E. faecalis viability was assessed by two fluorescent dyes ( syto 9/propidium iodide ) to determine the ' proportion of viable bacteria ' ( PVB% ) and number of ' colony-forming units ' ( CFU ) . Mean values and 95 % confidence intervals ( CI ) were calculated for PVB% and log CFU , and the difference between groups was established . RESULTS Viable and dead bacterial cells were detected in all ' rd ' sample s at weeks 4 and 8 . The treatment with CHX-gel , CHX-GP and OCT-gel result ed in significantly lower PVB% values with 15.4 % , 3.5 % and 0 % , respectively . No growth ( CFU ) was recorded for these sample s at week 12 . When medicated by CH , the PVB% was increased without a corresponding change in CFUs . CONCLUSIONS In contrast to calcium hydroxide , both CHX - and octenidine-based intracanal medicaments were effective in decreasing the viability of E. faecalis . OCT showed the most favourable results and may have potential as an endodontic medicament Output:	According to the evidence available now , mixing CH with CHX does not significantly increase the antimicrobial activity of CH against E. faecalis . It appears that mixing CH with CHX does not improve its ex vivo antibacterial property as an intracanal medicament against E. faecalis .
MS212068	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Using a structured interview with 150 r and omly selected 14 - 16-year-olds and their parents , we found 20 who endorsed four or more manic symptoms of at least 2 days duration . Compared to the rest of the sample , these teenagers had significantly higher rates of attention deficit , conduct , and anxiety disorders and psychotic symptoms , and were seen as needing treatment by the interviewers . However , most of the pathology was endorsed by teenagers rather than parents . Other assessment s confirmed this group as dysphoric , impulsive and emotionally labile . We discuss the normative and diagnostic implication s of these findings though long-term follow-up is necessary to draw more certain conclusions Twenty percent of a cohort of 206 outpatient depressives with no past bipolar history switched during prospect i ve observation . These 41 prob and s developed manic periods on the average of 6.4 years ( median 4 , range 1 - 25 ) after their first depressive episode . The change in polarity occurred throughout the life span , but was most common in adolescence and early adulthood . The following variables were found useful in predicting this outcome : onset less than or equal to 25 years , bipolar family history , loaded pedigrees , precipitation by childbirth , hypersomnic-retarded phenomenology , and pharmacologically-mobilized hypomania . Although the respective sensitivities of these findings were relatively low ( 32 - 71 % ) , their specificities ranged from 69 % to 100 % for bipolar outcome ; the diagnostic specificity of any 3 of these variables when combined was 98 % . When compared with nonbipolar depression , bipolar disorder was seldom chronologically secondary to nonaffective psychiatric disorders . These findings suggest that many young depressives with lethargy and oversleeping are not manifesting a " neurotic " disorder , but rather a precursor of primary bipolar affective disorder . Finally , a psychotically depressed adolescent or young adult with positive bipolar family history should be observed for eventual bipolar outcome , especially when the clinical presentation is that of stupor CONTEXT There is growing evidence that major depressive disorder ( MDD ) might be overdiagnosed at the expense of bipolar disorder ( BPD ) . OBJECTIVES To identify a subgroup of subthreshold BPD among DSM-IV MDD , which is distinct from pure MDD regarding a range of validators of bipolarity , and to examine the pattern of these validators among different groups with affective disorders . DESIGN Ten-year prospect i ve longitudinal and family study including 3 follow-up waves . Data were assessed with the DSM-IV Munich Composite International Diagnostic Interview . SETTING Community sample in Munich , Germany . PARTICIPANTS A total of 2210 subjects ( aged 14 - 24 years at baseline ) who completed the third follow-up . MAIN OUTCOME MEASURES Cumulative incidence of pure MDD , BPD , and subthreshold BPD ( defined as fulfilling criteria for MDD plus having manic symptoms but never having met criteria for [hypo]mania ) . RESULTS Among 488 respondents with MDD , 286 ( 58.6 % ) had pure MDD and 202 ( 41.4 % ) had subthreshold BPD ( cumulative incidence , 9.3 % ) . Compared with respondents who had pure MDD , respondents with subthreshold BPD were found to have a significantly increased family history of mania , considerably higher rates of nicotine dependence and alcohol use disorders , rates of panic disorder that were twice as high , and a tendency toward higher rates of criminal acts . Prospect i ve analyses showed that subthreshold BPD converted more often into BPD during follow-up , with DSM-IV criterion D ( symptoms observable by others ) being of critical predictive relevance . With increasing severity of the manic component , rates for diverse validators accordingly increased ( eg , alcohol use disorders , parental mania ) or decreased ( harm avoidance ) . CONCLUSIONS Data suggest that MDD is a heterogeneous concept including a large group with subthreshold BPD , which is clinical ly significant and shares similarities with BPD . Findings might support the need for a broader concept and a more comprehensive screening of bipolarity , which could be substantial for future research and adequate treatment of patients with bipolarity OBJECTIVES Significant questions remain regarding both the incidence patterns of mood episodes in adolescents and young adults from the community and the conversion rate from unipolar to bipolar disorders . We addressed these issues by examining data from a prospect i ve longitudinal community study to ( i ) determine the cumulative incidence of mood episodes and disorders in the first three decades of life ; ( ii ) determine the risk for first onset of depression among individuals with a previous history of hypomanic/manic episodes and vice versa ; and ( iii ) determine the clinical and treatment characteristics of these subjects . METHODS Using the Munich-Composite International Diagnostic Interview , clinical ly trained interviewers assessed mood episodes and mental disorders in 3,021 community subjects ( aged 14 - 24 at baseline and 21 - 34 at third follow-up ) . RESULTS The estimated cumulative incidence at age 33 was 2.9 % for manic , 4.0 % for hypomanic , 29.4 % for major depressive , and 19.0 % for minor depressive episodes ; overall , 26.0 % had unipolar major depression , 4.0 % bipolar depression , 1.5 % unipolar mania , and 3.6 % unipolar hypomania ( no major depression ) . Overall , 0.6 % and 1.8 % had unipolar mania or hypomania , respectively , without indication for even minor depression . A total of 3.6 % of the initial unipolar major depression cases subsequently developed (hypo)mania , with particularly high rates in adolescent onset depression ( < 17 years : 9 % ) . A total of 49.6 % of the initial unipolar mania cases subsequently developed major depression and 75.6 % major or minor depression . While bipolar cases had more adverse clinical and course depression characteristics and higher treatment rates than unipolar depressed cases , bipolar cases did not significantly differ in mania characteristics from unipolar mania cases . CONCLUSIONS Unipolar and bipolar mood disorders are more frequent than previously thought in adolescence and young adulthood , a time period when both the recognition and the intervention rates by the healthcare system are rather low . ' Conversion ' to bipolar disorder is limited in initial unipolar depression , but common in initial unipolar mania . The remaining unipolar mania cases appear to be significant in terms of clinical and course characteristics and thus require more research attention to replicate these findings OBJECTIVES To analyse the time course and some risk factors for a diagnostic change from major depression to bipolar disorders ( BP ) over an average of 20 years from the onset of the disorders . METHODS Patients ( 406 ) with major mood disorders hospitalised at some time between 1959 and 1963 were followed-up until 1985 . The analysis also included the course prior to hospitalisation . Survival analyses and Cox regression models were applied . RESULTS A diagnostic change from depression to bipolar I occurred in about 1 % of the patients per year and to bipolar II disorders in about 0.5 % per year . Risk factors for a change from depression to BP-I disorder were male sex and an early onset of the disorder ; risk factors for a change from depression to BP-II disorder were female sex , a later onset of the disorder and a positive family history of mania . CONCLUSIONS Across the entire lifetime , every new episode of depression brings a new risk for mania ; more than half of our severe mood disorder cases became bipolars . The risk of depression developing into bipolar disorder remains constant lifelong . LIMITATIONS The diagnostic classification of ICD-9 met RDC criteria for bipolar disorder in only 90 % of cases . Part of the data collected in retrospect may be less reliable ; the prospect i ve data were only collected every 5 years from 1965 to 1985 using multiple sources ; mild manifestations between the follow-ups may have been partially missed . The sample of subsequent hospital admissions for major depression and mania represents a severe group of patients and generalisations to ambulatory cases may not be possible . Not all risk factors for diagnostic conversion described in the literature could be assessed in this study INTRODUCTION We have developed ultra-high risk criteria for bipolar affective disorder ( bipolar at-risk - BAR ) which include general criteria such as being in the peak age range of the onset of the disorder and a combination of specific criteria including sub-threshold mania , depressive symptoms , cyclothymic features and genetic risk . In the current study , the predictive validity of these criteria were tested in help-seeking adolescents and young adults . METHOD This medical file-audit study was conducted at ORYGEN Youth Health ( OYH ) , a public mental health program for young people aged between 15 and 24years and living in metropolitan Melbourne , Australia . BAR criteria were applied to the intake assessment s of all non-psychotic patients who were being treated in OYH on 31 January , 2008 . All entries were then checked for conversion criteria . Hypomania/mania related additions or alterations to existing treatments or initiation of new treatment by the treating psychiatrist served as conversion criteria to mania . RESULTS The BAR criteria were applied to 173 intake assessment s. Of these , 22 patients ( 12.7 % ) met BAR criteria . The follow-up period of the sample was 265.5days on average ( SD 214.7 ) . There were significantly more cases in the BAR group ( 22.7 % , n=5 ) than in the non-BAR group ( 0.7 % , n=1 ) who met conversion criteria ( p<.001 ) . CONCLUSIONS These findings support the notion that people who develop a first episode of mania can be identified during the prodromal phase . The proposed criteria need further evaluation in prospect i ve clinical trials OBJECTIVE To investigate the rate and predictors of onset of DSM-III bipolar I and bipolar II disorders among 6- to 12-year-old prepubertal subjects with DSM-III major depressive disorder ( MDD ) who were followed for a 2- to 5-year period . METHODS This was a prospect i ve , blindly rated study of 79 children with MDD and 31 normal control children matched for age , gender , and socioeconomic status . Subjects and a second informant were assessed at 4-month intervals using the Kiddie Schedule for Affective Disorders and Schizophrenia-Present Episode Version-1986 modified to include 4-month interval ratings and to include DSM-III diagnoses . Family history ( FH ) was assessed using the FH- Research Diagnostic Criteria obtained from the mother about the subject 's first- and second-degree relatives . RESULTS Bipolarity developed in 31.7 % ( N = 25 ) of the children with MDD at a mean age of 11.2 + /- 2.0 years and 80 % were prepubertal . Loaded FH and multigenerational FH were significantly associated with bipolar I. Neither prior nor current use of tricyclic antidepressants nor atypical depressive features were predictive . CONCLUSIONS These findings strongly support the need to educate families of children with prepubertal-onset MDD about the possibility of the emergence of manic and hypomanic symptoms to encourage early recognition and appropriate treatment BACKGROUND To investigate whether ADHD is a risk factor for switches from unipolar to bipolar disorder over time . METHODS Data from two large controlled longitudinal family studies of boys and girls with and without ADHD and their siblings were used . Subjects ( n=168 ) were followed prospect ively and blindly over an average follow-up period of 7 years . Comparisons were made between youth with unipolar major depression who did and did not switch to full or subthreshold BP-I disorder at the follow-up assessment . Subjects were assessed at baseline and follow-up on multiple domains of functioning . Positive family history of parental psychiatric disorders was also compared between groups . RESULTS ADHD was associated with a significantly higher risk for switches from unipolar to bipolar disorder ( 28 % versus 6 % ; z=2.80 , p=0.005 ) . In subjects with ADHD , switches from unipolar to bipolar disorder were predicted by baseline comorbid conduct disorder , school behavior problems , and a positive family history of parental mood disorder . LIMITATIONS Psychosis was an exclusionary criterion in the original ascertainment of the studies of ADHD prob and s , so we were unable to test this as a predictor of switching to BPD . CONCLUSIONS ADHD is a risk factor for switches from unipolar to bipolar disorder , and switches could be predicted by the presence of baseline conduct disorder , school behavior problems , and a positive family history of a mood disorder in a parent . These characteristics can aid clinicians in their treatment of youth with MDD Output:	These findings can aid clinicians in differentiating the two forms of MDD in youth
MS212069	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND The efficacy and side-effect profile of ulipristal acetate as compared with those of leuprolide acetate for the treatment of symptomatic uterine fibroids before surgery are unclear . METHODS In this double-blind noninferiority trial , we r and omly assigned 307 patients with symptomatic fibroids and excessive uterine bleeding to receive 3 months of daily therapy with oral ulipristal acetate ( at a dose of either 5 mg or 10 mg ) or once-monthly intramuscular injections of leuprolide acetate ( at a dose of 3.75 mg ) . The primary outcome was the proportion of patients with controlled bleeding at week 13 , with a prespecified noninferiority margin of -20 % . RESULTS Uterine bleeding was controlled in 90 % of patients receiving 5 mg of ulipristal acetate , in 98 % of those receiving 10 mg of ulipristal acetate , and in 89 % of those receiving leuprolide acetate , for differences ( as compared with leuprolide acetate ) of 1.2 percentage points ( 95 % confidence interval [ CI ] , -9.3 to 11.8 ) for 5 mg of ulipristal acetate and 8.8 percentage points ( 95 % CI , 0.4 to 18.3 ) for 10 mg of ulipristal acetate . Median times to amenorrhea were 7 days for patients receiving 5 mg of ulipristal acetate , 5 days for those receiving 10 mg of ulipristal acetate , and 21 days for those receiving leuprolide acetate . Moderate-to-severe hot flashes were reported for 11 % of patients receiving 5 mg of ulipristal acetate , for 10 % of those receiving 10 mg of ulipristal acetate , and for 40 % of those receiving leuprolide acetate ( P<0.001 for each dose of ulipristal acetate vs. leuprolide acetate ) . CONCLUSIONS Both the 5-mg and 10-mg daily doses of ulipristal acetate were noninferior to once-monthly leuprolide acetate in controlling uterine bleeding and were significantly less likely to cause hot flashes . ( Funded by PregLem ; Clinical Trials.gov number , NCT00740831 . ) OBJECTIVE To investigate the effect of 2 medications ; Diphereline and Cabergoline , on uterine leiomyoma growth , and its histologic , sonographic , and intra-operative changes . METHODS In an effort to treat large uterine leiomyoma in symptomatic patients in the Gynecology Clinics of the Alzahra Teaching Hospital of Tabriz University of Medical Sciences , Tabriz , Iran , from September 2007 to November 2008 , 60 c and i date s r and omized to receive Diphereline 3.75 mg , 4 times every 28 days ( group I ) , and Cabergoline 0.5 mg , once a week for 6 weeks ( group II ) , were included in this study . Clinical symptoms , feasibility of intra-operative dissection , intraoperative complications , sonographic , and pathologic characteristics of the tumor were evaluated . RESULTS Thirteen patients from group I , and 10 patients from group II underwent surgery . There was a significant difference between the groups in the rate of lymphocyte infiltration ( p=0.003 ) , but not in other pathologic features . In both groups , the mitotic index was between 0 - 10 . While there was no significant difference between the groups in the number ( p=0.30 ) , and volume of leiomyomas ( p=0.65 ) , however , changes in the uterine artery circulation was significant ( p=0.001 [ group I ] , p=0.026 [ group II ] ) . In addition , there was a significant difference between the groups for intra-operative hemorrhage and adhesion of leiomyomas to the uterine wall . CONCLUSION This study found that Cabergoline is as effective as Diphereline in the shrinkage of myomas , accompanied by improvement in the sonographic , clinical , and intra-operative outcomes without any adverse pathological changes , and could be a good medical regimen as an adjunct to surgical management A. J. M. AUDEBERT , P. MADENELAT * , D. Q U E R L E U ? , G. P O N T O N N I E R ~ , C . R A C I N E T ~ , R.R E N A U D ~ , J.-Y. GILLET * * , D. R A U D R A N T ? ~ , J. LANSAC:~ , J.-P. B R E T T E ~ Cnbitiet Medical . Bordeaus : * Hdpital Bichat , Paris ; ? Centre Hospitalier , Roubai.r ; 1 Hdpital de la Grave , Toulouse ; $ Centre Hospiialier Sud , Ecliirolles : Hfipital Central , Strasbourg ; * * Hi?pital Saint Roch , Nice ; ttH6pital de I'Hdtel Dieu , Lyon ; : $ Hdpital de Tours , Tours ; and # Hipito1 Monwti . Brest . OBJECTIVE To assess the reproductive outcomes after minilaparotomic and laparoscopic myomectomy in patients wishing to conceive . DESIGN R and omized controlled trial . SETTING Departments of obstetrics and gynecology of the universities of Catanzaro , Rome , and Florence , Italy . PATIENT(S ) One hundred thirty-six women with symptomatic uterine leiomyomas or unexplained infertility . INTERVENTION(S ) Laparoscopic and minilaparotomic myomectomy . MAIN OUTCOME MEASURE(S ) Pregnancy , abortion , and live-birth rates . RESULT ( S ) Between the laparoscopic and minilaparotomic groups no difference was observed in cumulative pregnancy , live-birth , and abortion rates , whereas pregnancy and live-birth rates per cycle , and time to first pregnancy and live-birth were significantly higher in the laparoscopic than in the minilaparotomic group . Categorizing the patients according to surgical indication for myomectomy , cumulative pregnancy rate , pregnancy , and live-birth rates per cycle , and time to first pregnancy and live-birth were significantly better after laparoscopic myomectomy in symptomatic patients , whereas all reproductive outcomes were similar between the two groups in patients with unexplained infertility . CONCLUSION ( S ) Minilaparotomic and laparoscopic myomectomy improves in a similar manner the reproductive outcomes in patients with unexplained infertility , whereas the laparoscopic approach provides the best benefits in fertile patients with symptomatic leiomyomas Summary . Twenty‐four women with symptomatic multiple uterine myomas were allocated r and omly to treatment with buserelin , 1200μg/day intranasally , for 3 months followed by myomectomy ( n = 8) or to immediate myomectomy ( n = 16 ) . Pre‐operative treatment with buserelin reduced the mean uterine volume from 432 ( SD 165 ) to 242 ( SD 82 ) ml ( P < 0.01 ) but intra‐operative blood loss and postoperative morbidity were not significantly less in this group . Six months after operation , pelvic examination was normal in all the patients . However , ultrasonography with transvaginal probe demonstrated the presence of myomas of < 1.5 cm in five women ( 63 % ) treated pre‐operatively with the analogue and in two women ( 13 % ) who underwent immediate surgery ( P < 0.05 ) . Induction of a period of hypo‐oestrogenism before myomectomy seems to favour short‐term recurrence of uterine myomas , limiting the efficacy of surgery OBJECTIVE To ascertain whether adjuvant gonadotropin-releasing hormone ( GnRH ) agonist therapy decreases blood loss during abdominal myomectomy . DESIGN R and omized controlled trial . SETTING Academic reproductive surgery center . PATIENT(S ) One hundred premenopausal women requiring first-line conservative surgery for symptomatic intramural or subserous fibroids . INTERVENTION(S ) Eight weeks of treatment with depot triptorelin before myomectomy or immediate surgery . MAIN OUTCOME MEASURES Intraoperative blood loss , operating time , degree of difficulty of the procedure , and short-term rate of fibroid recurrence . RESULT ( S ) Mean ( + /-SD ) intraoperative blood loss was 265 + /- 181 mL in triptorelin recipients and 296 + /- 204 in patients who had immediate surgery ( mean difference , -31 mL [ 95 % CI , -108 to 46 mL ] ) . No significant differences were observed in blood loss according to uterine volume , number of fibroids removed , or total length of myometrial incisions . Most procedures in either group were of routine difficulty . On ultrasonography 6 months after myomectomy , four women in the GnRH agonist group and one in the immediate surgery group had tumor recurrence . CONCLUSION ( S ) Treatment with a GnRH agonist before abdominal myomectomy has no significant effect on intraoperative blood loss . Thus , systematic use of medical therapy before abdominal myomectomy does not seem to be justified OBJECTIVE To assess the usefulness of 3-month treatment with ulipristal acetate ( UPA ) before laparoscopic myomectomy of large uterine myomas . STUDY DESIGN This retrospective analysis of a prospect ively collected data base included women of reproductive age requiring laparoscopic myomectomy with the following characteristics : FIGO type 3 , 4 or 5 myomas ; largest diameter of the main myoma ≥10 cm ; number of myomas ≤3 ; largest diameters of the other myomas ≤5 cm ( second myoma ) and ≤3 cm ( third myoma ) . Patients either underwent direct surgery ( group S ) or were treated before surgery with UPA for 3 months ( group UPA ) . RESULTS The mean ( ±SD ) intraoperative blood loss was lower in group UPA ( 507.1±214.9ml ) than in group S ( 684.2±316.8 ; p=0.012 ) . The total operative time was lower in group UPA ( 137.6±26.8min ) than in group S ( 159.7±26.8min ; p<0.001 ) ; there was no significant difference in the suturing time between the two study groups ( p=0.076 ) . Hemoglobin drop was lower in group UPA ( 1.1±0.5g/dl ) than in group S ( 1.3±0.7g/dl ; p=0.034 ) . Six patients in group S and no patient in group UPA required postoperative blood transfusions ( p=0.031 ) . Complications were not different between the two groups ( p=0.726 ) . Moreover , preoperative treatment with UPA caused a significant increase in hemoglobin levels ( 11.9±1.6g/dl ) compared with baseline ( 9.1±1.1g/dl ; p<0.001 ) . CONCLUSION A 3-month treatment with UPA before laparoscopy for large uterine myomas decreases intraoperative blood loss , hemoglobin drop , postoperative blood transfusion and length of surgery Abstract The aim of this r and omised prospect i ve study was to investigate the impact of preoperative gonadotrophin-releasing hormone agonist ( GnRHa ) compared with a control group with myomectomy . A total of 36 women ( n = 36 , group 1 ) with fibroids were r and omised to receive either two monthly doses ( n = 18/36 , group 1a ) or three monthly doses of goserelin ( n = 18/36 , group 1b ) prior to myomectomy . The 32 women who received no treatment ( group 2 ) comprised the controls . All patients had similar demographic features . There were no significant differences among the three groups with respect to : ( 1 ) mean intraoperative blood loss ; ( 2 ) preoperative and postoperative blood transfusion or ( 3 ) length of hospital stay . The only advantage of administering GnRHa prior to myomectomy for symptomatic fibroids in our population was a higher haemoglobin level prior to surgery among the women who received three doses of the drug Objectives To evaluate the efficacy and safety of 2.5 mg and 5 mg mifepristone during 3 months for the treatment of uterine fibroids before surgery . Design Multicenter r and omized clinical trial . Locations Eusebio Hernández Hospital , Havana , Cuba and the Alemán Hospital , Managua , Nicaragua . Subjects Included in the study were 146 women with symptomatic uterine fibroids . Treatment Group I : half a tablet of 5 mg ( 2.5 mg ) mifepristone taken orally every 24 hours , and Group II : one tablet of 5 mg mifepristone taken orally every 24 hours over a period of 3 months in both groups . Two endometrial biopsies were performed . Variables to evaluate efficacy Increase in average hemoglobin , changes in fibroid and uterine volume , and symptomatic improvement . Results The average hemoglobin at the end Output:	Conclusion Administration of GnRHa prior to laparotomic myomectomy reduces blood loss and might decrease uterine adhesion formation .
MS212070	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The objective of this study was to determine the impact of stress reduction on blood pressure ( BP ) in adolescents by the Transcendental Meditation ( TM ) program . African-American adolescents ( aged 16.2 + /- 1.3 years ) with high normal systolic BP were r and omly assigned to either 4-month TM ( n = 50 ) or health education control ( n = 50 ) groups . Ambulatory 24-h BP measures were recorded at pretest , 2- and 4-month post-tests , and 4-month follow-up . Greater decreases in daytime systolic BP ( P < .04 ) and diastolic BP ( P < .06 ) in the TM group compared with the control group across the visits demonstrate a beneficial impact of the TM program in youth at risk for the development of hypertension Background Slow , controlled breathing has been shown by cross-spectral techniques to potentiate arterial baroreflex control of heart rate . However , crucial aspects of the effects of slow breathing on the arterial baroreflex remain unsettled , namely whether the major function of the arterial baroreflex ( i.e. the control of blood pressure ) is also potentiated and whether baroreflex function is differentially modulated according to the age of the individual . Objective To examine the bradycardic and depressor responses to selective carotid baroreceptor stimulation by the neck chamber technique ( −15 and −30 mmHg neck suction ) and the cross-spectral R – R interval/systolic blood pressure relationship ( α index ) . Methods In 24 resting , supine healthy male volunteers ( aged 19–66 years , mean ±SEM 37.5 ± 3.19 years ) , blood pressure ( Finapres ) , R – R interval ( electrocardiogram ) and ventilation ( impedance ) were recorded continuously . Both assessment s were performed during spontaneous breathing and during 6 cycles/min controlled ventilation in r and om order . Results The depressor and bradycardic responses to neck suction were significantly larger during slow breathing than in spontaneous breathing ( + 32 and + 85 % , respectively ; both P < 0.01 ) . The α index was also significantly larger during slow breathing ( + 62 % ; P < 0.01 ) . Even after the volunteers were divided into older ( > 50 years , n = 9 ) and younger ( < 30 years , n = 9 ) groups , the baroreflex potentiation related to slow breathing was clearcut and significant for both the depressor ( + 46 and + 24 % older and younger volunteers ; both P < 0.01 ) and the bradycardic ( + 130 and + 73 % older and younger volunteers ; both P < 0.01 ) responses . When the assessment was made by computing the cross-spectral α index , a marked potentiation related to slow breathing was observed in younger volunteers ( + 99 % ; P < 0.01 ) , whereas in older volunteers only a trend to an enhancement ( by 32 % ; P < 0.055 ) was observed . Conclusions Slow controlled breathing is associated with potentiation of both the depressor and the cardio-inhibitory components of the arterial baroreflex , the potentiation being largely similar regardless of the age of the individual In man evaluation of neural cardiovascular regulation makes use of a variety of tests which address the excitatory and reflex inhibitory neural influences that control circulation . Because interpretation of these tests is largely based on the magnitude of the elicited haemodynamic responses , their reproducibility in any given subject is critical . In 39 subjects with continuous blood pressure ( intra-arterial catheter ) and heart rate monitoring we measured the blood pressure and heart rate rises during h and -grip and cold-pressor test , the heart rate changes occurring during baroreceptor stimulation and deactivation by injection of phenylephrine and trinitroglycerine , and the heart rate and blood pressure changes occurring with alteration in carotid baroreceptor activity by a neck chamber . Each test was carefully st and ardized and performed at 30 min intervals for a total of six times in each subject . The results showed that the responses to any test were clearly different from one another and that this occurred in all subjects studied . For the group as a whole the average response variability ( coefficient of variation ) ranged from 10.2 % for the blood pressure response to carotid baroreceptor stimulation to 44.2 % for the heart rate response to cold-pressor test . The variability of the responses was not related to basal blood pressure or heart rate , nor to the temporal sequence of the test performance . Thus tests employed for study ing neural cardiovascular control in man produce responses whose reproducibility is limited . This phenomenon may make it more difficult to define the response magnitude typical of each subject , as well as its comparison in different conditions and diseases OBJECTIVE --To establish whether stress management had a larger effect than a control treatment on resting blood pressure , ambulatory blood pressure , and left ventricular mass . DESIGN --A 12 week baseline period of habituation to measurement of blood pressure was followed by r and omisation to either stress management or mild exercise for six months and follow up six months later . SETTING --General practice , district general hospital , and medical school . PATIENTS --Of the 184 patients aged under 60 with mild primary hypertension who entered the baseline habituation period , 88 were excluded because they failed to meet the entry criteria or they withdrew from the study . The remaining 46 men and 50 women underwent treatment . INTERVENTIONS --10 clinical sessions and daily practice at home of either stress management based on relaxation or non-aerobic stretching exercises . Mildly stressful 15 minute interviews before and after treatment . MAIN OUTCOME MEASURES --Diastolic and systolic blood pressure in the clinic and during 12 hours of ambulatory recording , and left ventricular mass measured by echocardiography . RESULTS --The patients ' blood pressure fell during habituation ( systolic pressure from 152 mmHg to 140 mmHg , diastolic pressure from 98 to 93 mm Hg ) , but neither resting nor ambulatory blood pressure was changed by the treatments . Left ventricular mass was also unchanged . Blood pressure rose during the stressful interview , but this rise was reduced by stress management ( systolic pressure rose by 7.4 mmHg before treatment and by 3.7 mmHg after treatment ) . CONCLUSION --Stress management of a type advocated for treating mild primary hypertension is ineffective in lowering blood pressure in patients who are well habituated to measuring blood pressure 34 hypertensive patients were assigned at r and om either to six weeks ' treatment by yoga relaxation methods with bio-feedback or to placebo therapy ( general relaxation ) . Both groups showed a reduction in blood-pressure ( from 168/100 to 141/84 mm . Hg in the treated group and from 169/101 to 160/96 mm Hg in the control group ) . The difference was highly significant . The control group was then trained in yoga relaxation , and their blood-pressure fell to that of the other group ( now used as controls ) BACKGROUND In chronic heart failure ( CHF ) , impaired pulmonary function can independently contribute to oxygen desaturation and reduced physical activity . We investigated the effect of breathing rate on oxygen saturation and other respiratory indices . METHODS Arterial oxygen saturation ( SaO2 ) and respiratory indices were recorded during spontaneous breathing ( baseline ) and during controlled breathing at 15 , six , and three breaths per min in 50 patients with CHF and in 11 healthy volunteers ( controls ) . 15 patients with CHF were r and omly allocated 1 month of respiratory training to decrease their respiratory rate to six breaths per min . Respiratory indices were recorded before training , at the end of training , and 1 month after training . FINDINGS During spontaneous breathing , mean SaO2 was lower in CHF patients than in controls ( 91 - 4 % [ SD 0.4 ] vs 95.4 % [ 0.2 ] , p<0.001 ) . Controlled breathing increased SaO2 at all breathing rates in patients with CHF . Compared with baseline , minute ventilation increased at 15 breaths per min ( + 45.9 % [ 9.8 ] , p<0.01 ) , did not change at six breaths per min , and decreased at three breaths per min ( -40.3 % [ 4.8 ] , p<0.001 ) . In the nine CHF patients who had 1 month of respiratory training , resting SaO2 increased from 92.5 % ( 0.3 ) at baseline to 93.2 % ( 0.4 ) ( p<0.05 ) , their breathing rate per min decreased from 13.4 ( 1.5 ) to 7.6 ( 1.9 ) ( p<0.001 ) , peak oxygen consumption increased from 1157 ( 83 ) to 1368 ( 110 ) L/min ( p<0.05 ) , exercise time increased from 583 ( 29 ) to 615 ( 23 ) min/s ( p<0.05 ) , and perception of dyspnoea reduced from a score of 19.0 ( 0.4 ) to 17.3 ( 0.9 ) on the Borg scale ( p<0.05 ) . There were no changes in the respiratory indices in the patients who did not have respiratory training . INTERPRETATION Slowing respiratory rate reduces dyspnoea and improves both resting pulmonary gas exchange and exercise performance in patients with CHF CONTEXT Weight loss , sodium reduction , increased physical activity , and limited alcohol intake are established recommendations that reduce blood pressure ( BP ) . The Dietary Approaches to Stop Hypertension ( DASH ) diet also lowers BP . To date , no trial has evaluated the effects of simultaneously implementing these lifestyle recommendations . OBJECTIVE To determine the effect on BP of 2 multicomponent , behavioral interventions . DESIGN , SETTING , AND PARTICIPANTS R and omized trial with enrollment at 4 clinical centers ( January 2000-June 2001 ) among 810 adults ( mean [ SD ] age , 50 [ 8.9 ] years ; 62 % women ; 34 % African American ) with above-optimal BP , including stage 1 hypertension ( 120 - 159 mm Hg systolic and 80 - 95 mm Hg diastolic ) , and who were not taking antihypertensive medications . INTERVENTION Participants were r and omized to one of 3 intervention groups : ( 1 ) " established , " a behavioral intervention that implemented established recommendations ( n = 268 ) ; ( 2 ) " established plus DASH,"which also implemented the DASH diet ( n = 269 ) ; and ( 3 ) an " advice only " comparison group ( n = 273 ) . MAIN OUTCOME MEASURES Blood pressure measurement and hypertension status at 6 months . RESULTS Both behavioral interventions significantly reduced weight , improved fitness , and lowered sodium intake . The established plus DASH intervention also increased fruit , vegetable , and dairy intake . Across the groups , gradients in BP and hypertensive status were evident . After subtracting change in advice only , the mean net reduction in systolic BP was 3.7 mm Hg ( P<.001 ) in the established group and 4.3 mm Hg ( P<.001 ) in the established plus DASH group ; the systolic BP difference between the established and established plus DASH groups was 0.6 mm Hg ( P = .43 ) . Compared with the baseline hypertension prevalence of 38 % , the prevalence at 6 months was 26 % in the advice only group , 17 % in the established group ( P = .01 compared with the advice only group ) , and 12 % in the established plus DASH group ( P<.001 compared with the advice only group ; P = .12 compared with the established group ) . The prevalence of optimal BP ( < 120 mm Hg systolic and < 80 mm Hg diastolic ) was 19 % in the advice only group , 30 % in the established group ( P = .005 compared with the advice only group ) , and 35 % in the established plus DASH group ( P<.001 compared with the advice only group ; P = .24 compared with the established group ) . CONCLUSION Individuals with above-optimal BP , including stage 1 hypertension , can make multiple lifestyle changes that lower BP and reduce their cardiovascular disease risk Output:	There is at present insufficient good- quality evidence to conclude whether or not TM has a cumulative positive effect on blood pressure
MS212071	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: A comparison of cycle control , efficacy and tolerability of two oral contraceptive preparations containing 20 microg ethinylestradiol combined with either 100 microg levonorgestrel ( EE/LNG 20/100 ) or 500 microg norethisterone ( EE/NET 20/500 ) was conducted . These results were compared to a st and ard reference preparation , containing 30 microg ethinylestradiol combined with 150 microg levonorgestrel ( EE/LNG 30/150 ) . Efficacy data from 8,544 treatment cycles were obtained from 767 women . Good cycle control and effective contraception was achieved with the two LNG preparations , however , the cycle control results were less favorable with EE/NET 20/500 . The cumulative incidence of women with at least one episode of intermenstrual bleeding from cycles 2 to 7 ( primary target variable ) was 43.9 % for EE/LNG 20/100 , 72.7 % for EE/NET 20/500 , and 15.7 % for the st and ard EE/LNG 30/150 . The difference between the 2 20 microg of EE preparations , which favored EE/LNG 20/100 , was statistically significant ( p = 0.001 ) . The overall spotting rates ( cycles 1 - 13 ) were 9.3 % for EE/LNG 20/100 , 21.7 % for EE/NET 20/500 , and 3.3 % for the st and ard EE/LNG 30/150 . Amenorrhea was reported in 7.1 % ( EE/LNG 20/100 ) , 20.6 % ( EE/NET 20/500 ) , and 0.9 % ( st and ard EE/LNG 30/150 ) , respectively . Intermenstrual bleeding episodes were shorter with EE/LNG 20/100 and EE/LNG 30/150 of the 13 treatment cycles . The study Pearl indices were 0.9 for EE/LNG 20/100 , 1.9 for EE/NET 20/500 , and 0.0 for EE/LNG 30/150 . All three treatments were well tolerated . However , tolerability was somewhat less favorable with EE/NET 20/500 . A total of 160 women prematurely discontinued the study for various reasons ( EE/LNG 20/100 : 7 % ; EE/NET 20/500 : 18 % ; EE/LNG 30/150 : 4 % ) . The overall adverse event incidence rate during the trial was low in all groups . Blood pressure remained largely unaffected . Thirteen serious adverse events were recorded for all treatment groups , all but one were assessed as not related to the treatments . There were no remarkable treatment related differences in mean body weight throughout the study and the laboratory values were largely unaffected in all three treatments groups In a parallel , multicenter study in Norway and Finl and involving a total of 196 healthy women ( mean age 22.4 years , range 18–30 ) , the effects on serum lipids and lipoproteins of two multiphasic oral contraceptives containing ethinyl estradiol ( EE ) but different progestins were examined . One formulation contained EE 35 μg and norethisterone ( NET ) 0.5 mg on days 1–7 and days 17–21 and elevated NET 1.0 mg during the midphase ( days 8–16 ) . The other formulation contained EE 30 μg on days 1–6 and days 12–21 and 40 μg on days 7–11 and phased levonorgestrel ( LGN ) : 50 μg ( days 1–6 ) , 75 μg ( days 7–11 ) and 125 μg ( days 12–21 ) . Both formulations induced significant elevation of total cholesterol ( 6.7 and 4.1 % ) , Apo B ( 8.1 and 7.0 % ) as well as HDL ( 6.4 and 3.7 % ) for the EE/NET and EE/LGN formulation respectively . Mean serum levels of triglycerides were significantly elevated ( 58 and 47 % ) . However , all mean serum lipid and lipoprotein values remained within the normal range , and no change in the calculated cholesterol ratio ( HDL/total cholesterol ) nor lipoprotein ratio ( HDL/(HDL+LDL ) ) was observed . No significant difference between the formulations could be detected with respect to the effect on serum lipids and lipoproteins measured . The change in total cholesterol was smaller than reported in many studies of monophasic preparations . Taken together , these data suggest that only small alterations in lipid metabolism are elicited by these oral contraceptives In an open , r and omized study in an outpatient clinic of a large teaching hospital , thirty-one female volunteers with regular cycles and established ovulation by ultrasonography were given one of two triphasic oral contraceptives containing ethinylestradiol combined with levonorgestrel or desogestrel during six cycles of treatment . The main outcome measures were transvaginal ultrasonography and serum E2 and P measurements in pill cycles 1 , 3 and 6 . No ovarian activity was found in 10 subjects . Among the remaining 21 women who showed ovarian activity , most follicle-like structures developed in the pill-free week and decreased in size or disappeared in the first pill week . One women taking triphasic desogestrel had evidence of a luteinized unruptured follicle and one women taking triphasic levonorgestrel had a possible ovulation . The latter women also showed symptoms of lower abdominal pain . A statistically significant difference in ovarian activity between the two oral contraceptives could not be established . The two triphasic oral contraceptives suppressed ovarian activity to the same degree . A trend was seen towards increasing ovarian activity with duration of use in both treatment groups 398 new users of oral contraceptives at the Research Clinic of the Southwest Foundation Texas were asked if they experienced nausea vomiting headache or breast discomfort nervousness or depression and had weight and blood pressure recorded in the pretreatment cycle and at monthly visits . Each received placebo Oracon ( sequential ) Ovulen-21 ( combination ) Norinyl-1 or .5 mg chlormadinone acetate in a double-blind protocol incorporating a pretreatment placebo cycle crossover to an active pill for 4 cycles and 2 more crossovers for Cyles 5 and 6 . The only symptoms significantly higher than in the pretreatment ( placebo ) cycle were nausea and vomiting with Oracon ( p greater than .05 ) and headache with Ovulen ( p greater than .05 ) . Pointing out that the highest incidence of complaints occurred in the placebo cycle the authors conclude that controls are necessary in contraceptive trials but the first cycle is not valid for comparison A phase III clinical study was carried out among 5680 fertile Chinese women to evaluate efficacy and side effects of three monthly injectable contraceptives : Mesigyna , Cyclofem and Chinese Injectable No. 1 . When used in a once-a-month treatment schedule ( part 1 of study ) , the effectiveness of Chinese Injectable No. 1 was unacceptably low ; 36 pregnancies occurred during the first 1743 women-months of use , 16 before the second injection . The study was restarted with a revised injection schedule for Injectable No. 1 : two injections separated by 9 + /- 1 days during the first month and subsequent injections given 10 - 12 days after the onset of bleeding , or if no bleeding occurred , 28 days after previous injection . In part 2 of the study , 988 , 990 and 992 subjects were provided Mesigyna , Cyclofem and Injectable No. 1 , respectively . Life-table pregnancy rates at one year were 0.41 % , 0 % and 0.77 % ( p < 0.05 ) , respectively ; the overall discontinuation rates at one year were 13.9 % , 19.1 % and 20.4 % ( p < 0.001 ) . Discontinuation rates for bleeding problems were significantly different between the groups : discontinuation rates for amenorrhea were 0.58 % , 3.71 % and 0.68 % ( p < 0.001 ) for Mesigyna , Cyclofem and Injectable No. 1 ; for other bleeding problems , the rates were 4.88 % , 8.38 % and 12.64 % ( p < 0.001 ) . There were no significant differences between the groups regarding discontinuation for other medical or non-medical reasons . Mean weight changes after one year of use were small : 0.73 , 0.86 and 0.17 kg for the three groups , respectively . Both Mesigyna and Cyclofem were very effective for contraception , but Mesigyna appeared to be tolerated slightly better with regard to cycle control ; the modified dose regimen for Injectable No. 1 also gave a low pregnancy rate but was associated with higher rates of discontinuation The efficacy and acceptability of two third generation oral contraceptives in Thai women were evaluated in a prospect i ve , open , group-comparative , r and omized , multicenter trial of women asking for contraception . In six Family Planning Centers and Outpatient Gynaecological Clinics in urban areas in Thail and , 783 healthy women who were at risk for pregnancy and did not have contraindications to oral contraceptive use were r and omly allocated to one of the two study groups . An oral contraceptive containing 30 mcg ethinylestradiol and 150 mcg desogestrel was given to 394 women and an oral contraceptive with the same amount of ethinylestradiol and 75 mcg gestodene to 389 women during 6 cycles . Criteria of cycle control , side effects and the presence and severity of acne vulgaris were assessed and blood pressure and body weight measured at pretreatment and after cycles 1 , 3 and 6 . Furthermore , the efficacy was evaluated after the last cycle . No pregnancies occurred with either of the contraceptives . The incidences of irregular bleeding and minor side effects in both groups were very low and decreased after an initial increase in the first cycle . Acne improved in both groups . Blood pressure and body weight remained unchanged . The two oral contraceptives were found to be effective and acceptable in Thai women . Compared to Caucasian women , the incidences of irregular bleeding and side effects were apparently lower in these Asian women . Furthermore , the effects of both oral contraceptives were comparable Blinding embodies a rich history spanning over two centuries . Most research ers worldwide underst and blinding terminology , but confusion lurks beyond a general comprehension . Terms such as single blind , double blind , and triple blind mean different things to different people . Moreover , many medical research ers confuse blinding with allocation concealment . Such confusion indicates misunderst and ings of both . The term blinding refers to keeping trial participants , investigators ( usually health-care providers ) , or assessors ( those collecting outcome data ) unaware of the assigned intervention , so that they will not be influenced by that knowledge . Blinding usually reduces differential assessment of outcomes ( information bias ) , but can also improve compliance and retention of trial participants while reducing biased supplemental care or treatment ( sometimes called co-intervention ) . Many investigators and readers naïvely consider a r and omised trial as high quality simply because it is double blind , as if double-blinding is the sine qua non of a r and omised controlled trial . Although double blinding ( blinding investigators , participants , and outcome assessors ) indicates a strong design , trials that are not double blinded should not automatically be deemed inferior . Rather than solely relying on terminology like double blinding , research ers should explicitly state who was blinded , and how . We recommend placing greater credence in results when investigators at least blind outcome assessment s , except with objective outcomes , such as death , which leave little room for bias . If investigators properly report their blinding efforts , readers can judge them . Unfortunately , many articles do not contain proper reporting . If an article cl aims blinding without any accompanying clarification , readers should remain sceptical about its effect on bias reduction The aim of this study was to compare contraceptive reliability , cycle control , and tolerance of an oral contraceptive containing 20 micrograms ethinylestradiol ( EE2 ) and 75 micrograms gestodene ( GSD ) , with a reference preparation containing a similar dose of gestodene but in combination with 30 micrograms ethinylestradiol . A higher incidence of intermenstrual bleeding was apparent under the 20 micrograms EE2 oral contraceptive . For the 20 micrograms EE2 preparation , 47.4 % of all women reported spotting at least once over a period of 12 treatment cycles , whereas this figure was 35.5 % for the 30 micrograms EE2 pill ( p < 0.05 ) . However , the incidence was within a range that corresponds to that of other OCs . The cumulative breakthrough bleeding rates ( at least once during the one year of treatment ) of 14.5 % ( 20 micrograms EE2 ) and 11.8 % ( 30 micrograms EE2 ) of women were not significantly different . In relation to all cycles , the intermenstrual bleeding rates were remarkably lower , indicating that the majority of the volunteers experienced such events only in few cycles under treatment : the spotting rate was 11.5 % ( 20 micrograms EE2 ) and 7.2 % ( 30 micrograms EE2 ) of all cycles , and the breakthrough bleeding rate was Output:	The 3 placebo-controlled , r and omized trials did not find evidence supporting a causal association between combination oral contraceptives or a combination skin patch and weight gain . In addition , discontinuation of combination contraceptives because of weight gain did not differ between groups when this factor was studied . : Available evidence is insufficient to determine the effect of combination contraceptives on weight , but no large effect is evident
MS212072	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Several studies in older people have shown that grip strength predicts all-cause mortality . The mechanisms are unclear . Muscle strength declines with age , accompanied by a loss of muscle mass and an increase in fat , but the role that body composition plays in the association between grip strength and mortality has been little explored . We investigated the relation between grip strength , body composition , and cause-specific and total mortality in 800 men and women aged 65 and over . METHODS During 197374 the UK Department of Health and Social Security surveyed r and om sample s of men and women aged 65 and over living in eight areas of Britain to assess the nutritional state of the elderly population . The survey included a clinical examination by a geriatrician who assessed grip strength and anthropometry . We used Cox proportional hazards models to examine mortality over 24 years of follow-up . RESULTS Poorer grip strength was associated with increased mortality from all-causes , from cardiovascular disease , and from cancer in men , though not in women . After adjustment for potential confounding factors , including arm muscle area and BMI , the relative risk of death in men was 0.81 ( 95 % CI 0.700.95 ) from all-causes , 0.73 ( 95 % CI 0.600.89 ) from cardiovascular disease , and 0.81 ( 95 % CI 0.660.98 ) from cancer per SD increase in grip strength . These associations remained statistically significant after further adjustment for fat-free mass or % body fat . CONCLUSION Grip strength is a long-term predictor of mortality from all-causes , cardiovascular disease , and cancer in men . Muscle size and other indicators of body composition did not explain these associations OBJECTIVES To examine the association between strength , function , lean mass , muscle density , and risk of hospitalization . DESIGN Prospect i ve cohort study . SETTING Two U.S. clinical centers . PARTICIPANTS Adults aged 70 to 80 ( N=3,011 ) from the Health , Aging and Body Composition Study . MEASUREMENTS Measurements were of grip strength , knee extension strength , lean mass , walking speed , and chair st and pace . Thigh computed tomography scans assessed muscle area and density ( a proxy for muscle fat infiltration ) . Hospitalizations were confirmed by local review of medical records . Negative binomial regression models estimated incident rate ratios ( IRRs ) of hospitalization for race- and sex-specific quartiles of each muscle and function parameter separately . Multivariate models adjusted for age , body mass index , health status , and coexisting medical conditions . RESULTS During an average 4.7 years of follow-up , 1,678 ( 55.7 % ) participants experienced one or more hospitalizations . Participants in the lowest quartile of muscle density were more likely to be subsequently hospitalized ( multivariate IRR=1.47 , 95 % confidence interval (CI)=1.24 - 1.73 ) than those in the highest quartile . Similarly , participants with the weakest grip strength were at greater risk of hospitalization ( multivariate IRR=1.52 , 95 % CI=1.30 - 1.78 , Q1 vs. Q4 ) . Comparable results were seen for knee strength , walking pace , and chair st and s pace . Lean mass and muscle area were not associated with risk of hospitalization . CONCLUSION Weak strength , poor function , and low muscle density , but not muscle size or lean mass , were associated with greater risk of hospitalization . Interventions to reduce the disease burden associated with sarcopenia should focus on increasing muscle strength and improving physical function rather than simply increasing lean mass BACKGROUND Hospitalization represents a stressful and potentially hazardous event for older persons . We evaluated the value of the Short Physical Performance Battery ( SPPB ) in predicting rates of functional decline , rehospitalization , and death in older acutely ill patients in the year after discharge from the hospital . METHODS Prospect i ve cohort study of 87 patients aged 65 years and older who were able to walk and with a Mini-Mental State Examination score ≥ 18 and admitted to the hospital with a clinical diagnosis of congestive heart failure , pneumonia , chronic obstructive pulmonary disease , or minor stroke . Patients were evaluated with the SPPB at hospital admission , were reevaluated the day of hospital discharge , and 1 month later . Subsequently , they were followed every 3 months by telephone interviews to ascertain functional decline , new hospitalizations , and vital status . RESULTS After adjustment for potential confounders , including self-report activity of daily living and comorbidity , the SPPB score at discharge was inversely correlated with the rate of decline in activity of daily living performance over the follow-up ( p < .05 ) . In a multivariable discrete-time survival analysis , patients with poor SPPB scores at hospital discharge ( 0 - 4 ) had a greater risk of rehospitalization or death ( odds ratio : 5.38 , 95 % confidence interval : 1.82 - 15.9 ) compared with those with better SPPB scores ( 8 - 12 ) . Patients with early decline in SPPB score after discharge also had steeper increase in activity of daily living difficulty and higher risk of rehospitalization or death over the next year . CONCLUSIONS In older acutely ill patients who have been hospitalized , the SPPB provides important prognostic information . Lower extremity performance-based functional assessment might identify older patients at high risk of poor outcomes after hospital discharge AIM The purpose of the present study was to investigate whether sarcopenia was associated with future falls in the general Japanese older population . METHODS This study was a 2-year prospect i ve observational study . Participants were recruited from individuals who had an annual town-sponsored medical check-up and had not received nursing care . The inclusion criteria for participants in our study were : ( i ) agreement to participate ; ( ii ) living independently ; and ( iii ) the ability to walk to where the survey was carried out and to provide self-reported data . A total of 223 residents ( 82 men , 141 women ) participated in the baseline assessment in the study . Demographic information , previous fall history , locomotive syndrome , body function and structural measurements and pain at the knee and /or lumber spine were assessed . The Asian Working Group for Sarcopenia algorithm was used to classify the presence of sarcopenia , and assess the history of falling when the participant received their annual medical check-up . RESULTS A total of 162 participants had an annual follow-up assessment , 50 of whom ( 30.8 % ) fell at least once during the 2-year observational period after baseline assessment . Previous falling history , prevalence of locomotive syndrome , sarcopenia and pain were significantly higher in participants who had fallen compared with participants who had not . Multiple logistic regression analysis showed the prevalence of sarcopenia was a significant predictor of falling . CONCLUSION The key finding of the present study suggests that sarcopenia is a risk factor for falling in older adults who are living independently even after adjustment for previous falls and confounding factors . Geriatr Gerontol Int 2017 ; 17 : 2124 - 2130 OBJECTIVES To evaluate the predictive value of muscle strength and physical performance in the oldest old for all-cause mortality ; hospitalization ; and the onset of disability , defined as a decline in activities of daily living ( ADLs ) , independent of muscle mass , inflammatory markers , and comorbidities . DESIGN A prospect i ve , observational , population -based follow-up study . SETTING Three well-circumscribed areas of Belgium . PARTICIPANTS Five hundred sixty participants aged 80 and older were followed for 33.5 months ( interquartile range 31.1 - 35.6 months ) . MEASUREMENTS Grip strength , Short Physical Performance Battery ( SPPB ) score , and muscle mass were measured at baseline ; ADLs at baseline and after 20 months ; and all-cause mortality and time to first hospitalization from inclusion onward . Kaplan-Meier curves and Cox proportional hazards models were calculated for all-cause mortality and hospitalization . Logistic regression analysis was used to determine predictors of decline in ADLs . RESULTS Kaplan-Meier curves showed significantly higher all-cause mortality and hospitalization in subjects in the lowest tertile of grip strength and SPPB score . The adjusted Cox proportional hazards model showed that participants with high grip strength or a high SPPB score had a lower risk of mortality and hospitalization , independent of muscle mass , inflammatory markers , and comorbidity . A relationship was found between SPPB score and decline in ADLs , independent of muscle mass , inflammation , and comorbidity . CONCLUSION In people aged 80 and older , physical performance is a strong predictor of mortality , hospitalization , and disability , and muscle strength is a strong predictor of mortality and hospitalization . All of these relationships were independent of muscle mass , inflammatory markers , and comorbidity Abstract Background The aim of this study is to assess the prevalence of sarcopenia and investigate the associations between sarcopenia and long‐term mortality and readmission in a population of elderly in patients in acute care wards . Methods We conducted a prospect i ve observational study in the acute care wards of a teaching hospital in western China . The muscle mass was estimated according to a previously vali date d anthropometric equation . H and grip strength was measured with a h and held dynamometer , and physical performance was measured via a 4 m walking test . Sarcopenia was defined according to the recommended diagnostic algorithm of the Asia Working Group for Sarcopenia . The survival status and readmission information were obtained via telephone interviews at 12 , 24 , and 36 months during the 3 year follow‐up period following the baseline investigation . Results Two hundred and eighty‐eight participants ( mean age : 81.1 ± 6.6 years ) were included . Forty‐nine participants ( 17.0 % ) were identified as having sarcopenia . This condition was similar in men and women ( 16.9 % vs. 17.5 % , respectively , P = 0.915 ) . During the 3 year follow‐up period , 49 men ( 22.7 % ) and 9 women ( 16.4 % ) died ( P = 0.307 ) . The mortality of sarcopenic participants was significantly increased compared with non‐sarcopenic participants ( 40.8 % vs. 17.1 % , respectively , P < 0.001 ) . After adjusting for age , sex and other confounders , sarcopenia was an independent predictor of 3 year mortality ( adjusted hazard ratio : 2.49 ; 95 % confidential interval : 1.25–4.95 ) and readmission ( adjusted hazard ratio : 1.81 ; 95 % confidential interval : 1.17–2.80 ) . Conclusions Sarcopenia , which is evaluated by a combination of anthropometric measures , gait speed , and h and grip strength , is valuable to predict hospital readmission and long‐term mortality in elderly patients in acute care wards BACKGROUND Sarcopenia is prevalent in older population s with many causes and varying outcomes however information for use in clinical practice is still lacking . AIMS The aim of this report is to identify the clinical determinants and prognostic significance of sarcopenia in a cohort of hospitalized acutely ill older patients . METHODS Four hundred and thirty two r and omly selected patients had their baseline clinical characteristic data assessed within 72 h of admission , at 6 weeks and at 6 months . Nutritional status was assessed from anthropometric and biochemical data . Sarcopenia was diagnosed from low muscle mass and low muscle strength-h and grip using anthropometric measures based on the European Working Group criteria . RESULTS Compared with patients without sarcopenia , those diagnosed with sarcopenia 44 ( 10 % ) were more likely to be older , have more depression symptoms and lower serum albumin concentration . The length of hospital stay ( LOS ) was significantly longer in patients diagnosed with sarcopenia compared with patients without sarcopenia [ mean ( SD ) LOS 13.4 ( 8.8 ) versus 9.4 ( 7 ) days respectively , p = 0.003 ] . The risk of non-elective readmission in the 6 months follow up period was significantly lower in patients without sarcopenia compared with those diagnosed with sarcopenia ( adjusted hazard ratio .53 ( 95 % CI : .32 to .87 , p = 0.013 ) . The death rate was also lower in patients without sarcopenia 38/388 ( 10 % ) , compared with those with sarcopenia 12/44 ( 27 % ) , p-value = .001 . CONCLUSION Older people with sarcopenia have poor clinical outcome following acute illness compared with those without sarcopenia Summary In this study , we compare the extent to which seven available definitions of sarcopenia and two related definitions predict the rate of falling . Our results suggest that the definitions of Baumgartner and Cruz-Jentoft best predict the rate of falls among sarcopenic versus non-sarcopenic community-dwelling seniors . Introduction The purpose of the study is to compare the extent to which seven available definitions of sarcopenia and two related definitions predict the prospect i ve rate of falling . Methods We studied a cohort of 445 seniors ( mean age 71 years , 45 % men ) living in the community who were followed with a detailed fall assessment for 3 years . For comparing the rate of falls in sarcopenic versus non-sarcopenic individuals , we used multivariate Poisson regression analyses adjusting for gender and treatment ( original intervention tested vitamin D plus calcium against placebo ) . Of the seven available definitions , three were based on low lean mass alone ( Baumgartner , Delmonico 1 and 2 ) and four required both low muscle mass and decreased performance in a functional test ( Fielding , Cruz Output:	Conclusions Sarcopenia is a significant predictor of hospitalization among older individuals , and the association may not be significantly affected by the characteristics of the population or the definition of sarcopenia
MS212073	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Although a model for shared decision-making is important for patient-centered care , decisional conflict can emerge when patients participate in the decision-making . A decision aid is proposed to provide information and to involve patients more comfortably in the decision-making process . We aim ed to determine whether a decision aid helps patients with carpal tunnel syndrome ( CTS ) experience less decisional conflict regarding their decision-making for surgery . Methods Eighty patients with CTS were r and omized into two groups . The test group was given a decision aid in addition to regular information and the control group regular information only . The decision aid consisted of a 6-min videoclip that explains diagnosis and information regarding surgery for CTS with other treatment options . We evaluated patients ’ decisional conflict regarding surgery , knowledge about CTS , and symptom severity as measured by the Disabilities of Arm , Shoulder , and H and ( DASH ) Question naire . Results There was no difference in the decisional conflict scale ( DCS ) between both groups ( p = 0.76 ) . The test group had significantly better knowledge than the control group ( p = 0.04 ) . There was no correlation between the knowledge score and the DCS ( p = 0.76 ) . However , less severe symptoms were correlated with greater decisional conflict ( r = −0.29 , p = 0.02 ) . Conclusions We found that a decision aid does not reduce decisional conflict in patients with CTS , although it can help them be better informed . This study suggests that although a decision-aid is effective for patient education , doctor-patient communication should be more emphasized for patients with less severe symptoms , as they can have greater decisional conflict . Trial Registration SNUBH Registry 1510/317 - 003 Registered November 13 , OBJECTIVE We aim ed to evaluate the effect of a decision aid ( DA ) with patient narratives on decisional conflict in surgery choice for Japanese women with early-stage breast cancer . METHODS Two hundred ten women with early-stage breast cancer were r and omly assigned to an intervention or control group . Groups 1 and 2 received st and ard information and a DA , with or without patient narratives , and Group 3 received st and ard information ( control ) before surgery choice . At baseline , post-intervention ( Time 2 ) , and 1 month after surgery ( Time 3 ) , we evaluated decisional conflict as the primary outcome using a decisional conflict scale ( DCS ) . Sidak corrections for multiple comparisons in analysis of covariate were used to compare Time 2 and Time 3 DCS mean scores between each pair of groups . RESULTS At Time 3 , decisional conflict was significantly reduced for Group 1 vs control ( P=0.021 , Cohen 's d = 0.26 ) and Group 2 vs control ( P=0.008 , Cohen 's d=0.40 ) . CONCLUSION The DAs with and without patient narratives are equivalently effective at reducing postoperative decisional conflict in Japanese women with early-stage breast cancer . PRACTICE IMPLICATION S The DAs with and without patient narratives can be used in clinical practice for women with early-stage breast cancer Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more ABSTRACT In order to increase patient active engagement during patient – provider interactions , we developed and implemented patient training sessions in four antiretroviral therapy ( ART ) clinics in Namibia using a “ Patient Empowerment ” training curriculum . We examined the impact of these trainings on patient – provider interactions after the intervention . We tested the effectiveness of the intervention using a r and omized parallel group design , with half of the 589 enrolled patients r and omly assigned to receive the training immediately and the remaining r and omized to receive the training 6 months later . The effects of the training on patient engagement during medical consultations were measured at each clinic visit for at least 8 months of follow-up . Each consultation was audiotaped and then coded using the Roter Interaction Analysis System ( RIAS ) . RIAS outcomes were compared between study groups at 6 months . Using intention-to-treat analysis , consultations in the intervention group had significantly higher RIAS scores in doctor facilitation and patient activation ( adjusted difference in score 1.19 , p = .004 ) , doctor information gathering ( adjusted difference in score 2.96 , p = .000 ) , patient question asking ( adjusted difference in score .48 , p = .012 ) , and patient positive affect ( adjusted difference in score 2.08 , p = .002 ) . Other measures were higher in the intervention group but did not reach statistical significance . We have evidence that increased engagement of patients in clinical consultation can be achieved via a targeted training program , although outcome data were not available on all patients . The patient training program was successfully integrated into ART clinics so that the trainings complemented other services being provided Background Chronic conditions are a major source of morbidity , mortality and cost worldwide . Shared decision making is one way to improve care for patients with chronic conditions . Although it has been widely studied , the effect of shared decision making in the context of chronic conditions is unknown . Methods / Design We will perform a systematic review with the objective of determining the effectiveness of shared decision making interventions for persons diagnosed with chronic conditions . We will search the following data bases for relevant articles : PubMed , Scopus , Ovid MEDLINE , Ovid EMBASE , Ovid EBM Review s CENTRAL , CINAHL , and Ovid PsycInfo . We will also search clinical trial registries and contact experts in the field to identify additional studies . We will include r and omized controlled trials study ing shared decision making interventions in patients with chronic conditions who are facing an actual decision . Shared decision making interventions will be defined as any intervention aim ing to facilitate or improve patient and /or clinician engagement in a decision making process . We will describe all studies and assess their quality . After adjusting for missing data , we will analyze the effect of shared decision making interventions on outcomes in chronic conditions overall and stratified by condition . We will evaluate outcomes according to an importance ranking informed by a variety of stakeholders . We will perform several exploratory analyses including the effect of author contact on the estimates of effect . Discussion We anticipate that this systematic review may have some limitations such as heterogeneity and imprecision ; however , the results will contribute to improving the quality of care for individuals with chronic conditions and facilitate a process that allows decision making that is most consistent with their own values and preferences . Trial registration PROSPERO Registration Number : PURPOSE Breast cancer ( BC ) decision aid ( DA ) r and omized studies are limited to DA use in consultations among Western population s and for primary surgery . Their effectiveness beyond consultations , for reconstructive surgery and in other population s , has not been evaluated . We developed a DA administered after consultation for Chinese women deciding on BC surgery and , where relevant , immediate breast reconstruction , which was evaluated in this r and omized controlled trial ( RCT ) . PATIENTS AND METHODS Overall , 276 women considering BC surgery for early-stage BC were r and omly assigned to receive a DA ( take-home booklet ) or the st and ard information booklet ( control condition ) after the initial consultation , wherein surgeons disclosed the diagnosis and discussed treatment options with patients . Using block r and om assignment by week , 138 women were assigned to the DA arm and 138 to the control arm . Participants completed interview-based question naires 1 week after consultation and then 1 , 4 , and 10 months after surgery . Primary outcome measures were decisional conflict , decision-making difficulties , BC knowledge 1 week after consultation , and decision regret 1 month after surgery . Secondary outcome measures were treatment decision , decision regret 4 and 10 months after surgery , and postsurgical anxiety and depression . RESULTS The DA group reported significantly lower decisional conflict scores 1 week after consultation ( P = .016 ) compared with women in the control arm . Women receiving the DA had significantly lower decision regret scores 4 ( P = .026 ) and 10 months ( P = .014 ) after surgery and lower depression scores 10 months after surgery ( P = .001 ) . CONCLUSION This RCT demonstrated DAs may benefit Chinese patients in Hong Kong by reducing decisional conflict and subsequent regret and enhance clinical services for this population OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity OBJECTIVE The objective of this study was to evaluate the patients ' perception of the usefulness of a question prompt sheet ( QPS ) in facilitating the involvement of advanced cancer patients during consultation . METHODS Advanced cancer patients attending their first consultation after diagnosis were r and omly assigned to the intervention group ( received QPS and a hospital introduction sheet ( HIS ) ) or the control group ( received HIS only ) . Analysis was conducted on an intention-to-treat basis . The primary outcome measure was patient rating of the usefulness of the material ( s ) ( numerical rating scale of 0 - 10 ) . RESULTS Sixty-three advanced cancer patients ( 72.4 % response rate ) were enrolled and analyzed . Nearly three-quarters of patients in both groups read the material ( s ) before consultation . The rated usefulness of the material ( s ) for asking questions of physicians was significantly higher in the intervention group than in controls ( 4.4 ± 3.6 and 2.7 ± 2.8 , respectively ; p = 0.033 ) . The mean score of the usefulness of the material ( s ) for underst and ing the treatment plan tended to be higher in the intervention group than in the controls ( 4.9 ± 3.6 and 3.3 ± 2.8 ; p = 0.051 ) . The mean score of willingness to use the material ( s ) in the future was significantly higher in the intervention group than in the controls ( 5.3 ± 3.8 and 2.8 ± 2.8 ; p = 0.006 ) . There were no significant differences between the groups in the average total number of questions asked by patients ( median , 1.0 ; interquartile range in both groups , 2.0 ) . CONCLUSIONS QPS provided before oncology consultation may be useful for advanced cancer patients , on the other h and , it did not directly promote patient confidence to ask questions Paternalistic models of health care , social distance between patients and providers , and cultural norms discourage patients from playing an active role in health consultations . This study tested whether individual coaching can give family planning patients the confidence and communication skills to talk more openly and more vigorously with providers . Educators met with 384 Indonesian women in clinic waiting rooms and coached them on asking questions , expressing concerns , and seeking clarification . An analysis of audiotaped consultations found that patients who received coaching articulated significantly more questions and concerns than others . Coaching narrowed differentials in active communication by patient type , age , and assertiveness , but it widened differentials by patient education and socioeconomic class . The discontinuation rate at 8 months was lower in the intervention than the control condition , but the difference was only marginally significant Background A patient decision aid ( PDA ) is a tool for shared decision making ( SDM ) , which emphasises patient empowerment . It is useful in chronic diseases and when there are multiple , no best single treatment option . Although SDM is prevalent in Western countries , its use is limited in Chinese societies , where the adoption of a paternalistic approach is strong . Here , we report the development , acceptance and pilot test results of a PDA targeted at Chinese patients with primary open-angle glaucoma ( POAG ) . Methods We developed a PDA design ed for use in Chinese patients with POAG . Recruited subjects were given our PDA . Baseline evaluation included decision conflict scale ( DCS ) , vali date d glaucoma adherence question naires and glaucoma knowledge question naire . Subjects were briefed through the PDA and instructed to read it that day . Three to four weeks later , follow-up question naire as described above were conducted with the addition of acceptance question naires . Results Data from 65 subjects were available . The PDA was well received among subjects . DCS improved from 48.9±20.4 at baseline to 34.3±2 Output:	Whilst most of the studies reported increased patient participation , those interventions which had provider or patient training in communication skills were found to be more effective . CONCLUSION Interventions to improve patient participation , within the context of dyadic decision making , in non-Western countries can be feasible and effective if communication skills training is provided for health-care providers and /or patients
MS212074	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Chronic thromboembolic pulmonary hypertension ( CTEPH ) is a rare but potentially life-threatening disease of the pulmonary circulation [ 1 ] . The pathogenesis of CTEPH is not entirely clear . The most accepted scenario is that of aborted recanalisation of pulmonary arteries after a thromboembolic episode . While some post-embolic residua may persist in up to 50 % of survivors of acute pulmonary embolism ( aPE ) , only 0.5 % to 2 % will progress to CTEPH [ 2 , 3 ] . This is believed to occur in the presence of significant redistribution of flow to remaining unoccluded pulmonary bed with result ing elevation of intravascular pressure and shear stress . Remodelling of initially patent pulmonary arterioles leads to an increase in pulmonary vascular resistance similar to that observed in left-to-right shunting in congenital heart disease . Progressive uncoupling of pulmonary and right ventricular elastance results in a fall of pulmonary flow , left ventricular preload , systemic blood pressure , and right ventricular ( RV ) coronary perfusion leading to right heart failure with severe functional disability and eventually to death . Management of CTEPH requires precise differential diagnosis and qualification for surgical treatment by an experienced multidisciplinary team . Indeed , in operable patients pulmonary endarterectomy ( PEA ) is highly effective in restoring functional status and improving life expectancy . A surgical technique has been optimised and implemented worldwide by a group from San Diego – University of California [ 4 ] . Nevertheless , PEA performed in deep hypothermia and intermittent total cardiac arrest remains one of the most dem and ing cardiovascular interventions and is performed only in a limited number of highly dedicated centres . As an example , Papworth Hospital is the only centre performing PEA in the UK , while Marie-Lannelongue Hospital in Paris remains a referral centre for France for this type of surgery . Usually , individual cardiac surgeons are responsible for PEA in their centres , as the learning curve for this intervention has been well documented [ 5 ] . With growing experience of clinicians , radiologists , surgeons , and anaesthesiologists , an increasing proportion of patients with CTEPH may benefit from PEA despite distal , less accessible intravascular residua and /or advanced age and comorbidities . This is of paramount importance since the outcome of non-operated patients is drastically worse ( Figure 1 ) , despite identical baseline haemodynamic characteristics and significant perioperative mortality of 2–10 % in patients su bmi tted to PEA [ 6 ] . Nevertheless , even in the leading CTEPH referral centres almost 50 % patients remain on medical treatment alone , with grim perspectives regarding life quality and expectancy . Based on a large r and omised trial and promising long-term effects on exercise tolerance [ 7 , 8 ] direct guanylyl cyclase stimulator ( riociguat ) has been approved for treatment of inoperable CTEPH . Riociguat may protect patent pulmonary arterioles from progressive remodelling [ 9 ] but is unlikely to affect the culprit post-embolic residua . Recently , balloon pulmonary angioplasty ( BPA ) has emerged as a promising new interventional option in non-operable CTEPH . In 2001 , Feinstein et al. from Harvard Medical School described a group of 18 CTEPH patients treated with BPA [ 10 ] . Of these , 16 were excluded from PEA due to distal lesions , and two due to the presence of comorbidities increasing the risk associated with surgical treatment . In total , 47 procedures were performed , thus dilating or restoring the patency of 107 arteries . In the periprocedural period , 1 patient died of reperfusion pulmonary oedema and right ventricular failure . In total , reperfusion oedema occurred in 23 % of cases , and its presence correlated with the value of pulmonary artery pressure ( PAP ) prior to the procedure . Long-term follow-up ( mean , 34 months ) showed an increase in physical capacity , manifesting itself as an improvement in NYHA class from a mean value of 3.3 prior to the procedure to a mean value of 1.8 following the procedure . Figure 1 Survival curves for patients with CTEPH treated with PEA ( shadow line ) and who were treated by pharmacotherapy only ( solid line ) – reprinted from Wieteska et al. [ 6 ] The succeeding years saw the development of the BPA technique mainly in Japanese centres . Japanese research ers have refined the BPA technique by reducing the number of segments treated during one session [ 11 ] , by using smaller balloons [ 12 ] , and by wider use of intravascular imaging [ 13 , 14 ] . The experience of the Japanese centres shows that a series of BPA procedures performed in experienced centres has lead to regression of right ventricular dysfunction [ 15 , 16 ] and are associated with an annual mortality below 5 % – also in elderly patients [ 17 ] . However , it should be stressed that the population of Japanese patients with CTEPH differs from that observed in the European-American registry [ 18 ] . In a registry comprising 519 Japanese patients with CTEPH , lower median pretreatment mPAP ( 38 mm Hg vs. 47 mm Hg ) , more frequent use of PAH-like therapy ( 52 % vs. 38 % ) , and a significantly lower rate of cardiac surgical treatment used ( 14 % vs. 57 % ) was observed [ 19 ] . The only larger group of patients in Europe who underwent BPA is that described by And reassen et al. [ 20 ] . The Norwegian team treated 20 CTEPH patients , including 16 with distal lesions , 3 with proximal lesions who had refused PEA , and 1 patient with persistent pulmonary hypertension following surgical treatment . Prior to treatment , 85 % of the patients presented with NYHA class III and IV symptoms . During recruitment to a percutaneous treatment program in the same centre , 50 PEAs were performed . In total , 73 BPA procedures were carried out ( mean , 3.7 BPAs/patient ; range : 2–9 ) , thus performing angioplasty of 371 vessels – 118 segmental arteries and 253 subsegmental arteries . In the periprocedural period , two patients died , and treatment-requiring reperfusion oedema occurred in 7 cases . During 3-month follow-up , an improvement in the functional class ( 75 % of patients in NYHA class I – II ) , in VO2max in cardiopulmonary exercise test ( 13.6 ±5.6 vs. 17.0 ±6.5 , p < 0.001 ) , in mean pulmonary artery pressure ( 45 ±11 mm Hg vs. 33 ±10 mm Hg , p < 0.001 ) , in pulmonary vascular resistance ( 8.8 ±4.0 Wood Units vs. 5.9 ±3.6 Wood Units , p < 0.001 ) , and in NT-pro-BNP levels ( 194 ±182 ng/ml vs. 90 ±119 ng/ml , p = 0.007 ) was achieved . Follow-up angiography revealed no restenosis . In Pol and , the first BPA procedure was performed in 2013 [ 21 ] . Until now , the experience of our team includes 37 BPA procedures , which consisted of angioplasty of 105 vessels in 20 patients with CTEPH . Seventeen patients were excluded from surgical treatment by an experienced PEA cardiac surgery team , and in 3 patients persistent pulmonary hypertension persisted after PEA . Eighty-two percent of patients received PAH-like therapy – most frequently sildenafil . In the periprocedural period , two patients died of severe reperfusion oedema and severe hypoxaemia unresponsive to oxygen therapy ( including mechanical ventilation ) . Those 2 patients were disqualified from PEA due to the presence of extensive lung cavities related to previous mycobacterial infection and due to significant comorbidities and advanced age , respectively – but not because of distal localisation of thrombi . All patients who underwent BPA because of distal lesion localisation survived . In technical terms , BPA does not significantly differ from balloon angioplasty performed in other vessels ( Figure 2 ) . Nevertheless , the complicated anatomy of the pulmonary tree , the necessity to advance the instruments through enlarged right heart chambers , and the fact that pulmonary vessels can be easily damaged with the guide wire or balloon catheter requires specific experience . It is not recommended that BPA procedures be performed by cardiologists or interventional radiologists who have experience in other vascular regions but no experience in interventions within the pulmonary circulation . During one procedure , no more than two segmental arteries or their subsegmental equivalents should be dilated due to the risk of reperfusion oedema . Reperfusion oedema results from redistribution of blood flow to areas supplied by dilated vessels , in which vascular resistance has abruptly decreased . This may cause blood cells to migrate into the alveoli , excluding them from gas exchange . One way to prevent reperfusion oedema is to undersize the balloon catheter being used , on the basis of angiography , or by means of intravascular ultrasound ( IVUS ) or optical coherence tomography ( OCT ) . Also , pressure distal to a residual lesion and a gradient across the lesion can be measured by means of an fractional flow reserve ( FFR ) probe [ 22 ] . As there is no tendency towards restenosis , it is unnecessary to use stents . The results achieved in the group of patients who have completed a series of BPA procedures are very encouraging . A reduction in mean PAP from baseline 58 ±6 mm Hg to 41 ±9 mm Hg and in PVR from 11.7 ±4.3 Wood units to 6.6 ±2.2 Wood units was achieved in our series . The haemodynamic improvement corresponds with an improvement in exercise tolerance . Prior to BPA procedures , 95 % of patients were in NYHA class III and IV , and the rate of patients in class III and IV decreased to 35 % after treatment . A significant issue limiting growth in the number of such procedures performed in Pol and is that BPA is not reimbursed by the National Health Fund . Figure 2 Balloon pulmonary angioplasty in a 67-year-old patient with persistent form of CTEPH . Left panel ( A ) presents the angiogram of occluded segmental pulmonary artery of left lower lobe . The BPA results in reperfusion of the vessel – right panel ( To use cardiac magnetic resonance imaging ( MRI ) to investigate the effect of balloon pulmonary angioplasty ( BPA ) on interventricular dyssynchrony and its associations with ventricular interaction , which impairs LV function in patients with inoperable chronic thromboembolic pulmonary hypertension ( CTEPH ) . This prospect i ve observational study was approved by our institutional review board . Cardiac MRI and right heart catheterization were conducted before BPA sessions and at the follow up after BPA in 20 patients with CTEPH . We measured right ventricular ( RV ) and left ventricular ( LV ) end-diastolic volume ( EDV ) , end-systolic volume ( ESV ) , stroke volume ( SV ) , and ejection fraction ( EF ) using MRI . For the LV and RV free walls , the time to peak ( Tpeak ) of circumferential strain was calculated as a parameter for interventricular dyssynchrony . Following BPA , the RV-EDV and -ESV were significantly decreased , and the RVEF was significantly increased . Conversely , BPA led to significantly increased LV EDV and SV without changing LVESV . The left-to-right free wall delay ( L – R delay ) in Tpeak strain decreased from 105 ± 44 ms to 47 ± 67 ms ( p < 0.001 ) . Increased LV EDV ( r = 0.65 , p < 0.01 ) , SV ( r = 0.74 , p < 0.001 ) and 6-minute walk distance ( 6MWD ) ( r = 0.54 , p < 0.05 ) were correlated to the reduction in L – R delay . In patients with inoperable CPEPH , BPA improved interventricular dyssynchrony , which was strongly associated with increased SV and 6MWD . The assessment of interventricular dyssynchrony using cardiac MRI has an important role in evaluating ventricular interaction , which reduces LVSV and exercise tolerance BACKGROUND Although balloon pulmonary angioplasty ( BPA ) improves the hemodynamics and prognosis of patients with inoperable chronic thromboembolic pulmonary hypertension ( CTEPH ) , the mechanisms of improvement in oxygenation remain to be eluci date d. METHODS AND RESULTS From August 2013 to May 2015 , we performed a total of 113 BPA procedures in 24 patients with inoperable CTEPH ( mean 4.7 procedures per patient ) . Median age was 70 [ 60 , 74 ] years and 18 were female ( 75 % ) . We examined hemodynamics , respiratory functions , and intrapulmonary shunt before and after the BPA procedure . Mean pulmonary arterial pressure ( 37 [ 28 , 45 ] to 23[19 , 27 ] mmHg , P<0.01 ) , pulmonary vascular resistance ( 517 [ 389 , 696 ] to 268 [ 239 , 345 ] dyne/s/cm(5 ) ) and 6-min walk distance ( 390 [ 286 , 484 ] to 490 [ 411 , Output:	The most common adverse events of riociguat were headache , dizziness , hypotension and nasopharyngitis . CONCLUSIONS Our meta- analysis indicates that BPA might be associated with greater improvements in exercise tolerance and pulmonary hemodynamics except for cardiac output and cardiac index than riociguat therapy . However , both of them were well tolerated
MS212075	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Previously , we and others showed that hypoxia‐inducible factor‐1α ( HIF‐1α ) and transcriptionally upregulated Aurora‐A were required for disease progression in several tumors . Here , we address the clinicopathologic value of Aurora‐A and HIF‐1α in locally advanced nasopharyngeal carcinoma ( NPC ) . Aurora‐A and HIF‐1α expression was semiquantitatively evaluated by immunohistochemistry staining in 144 cases from a r and omized controlled trial . Of these patients , 69 received neoadjuvant chemotherapy plus concurrent chemoradiotherapy , and acted as the training set , and 75 cases treated with neoadjuvant chemotherapy plus radiotherapy were used as the testing set to vali date the prognostic effect of Aurora‐A and HIF‐1α . We found that Aurora‐A and HIF‐1α were highly expressed in NPC , but were deficient in normal adjacent epithelia . In the testing set , Aurora‐A overexpression predicted a shortened 5‐year overall survival ( 59.1 % vs 82.5 % , P = 0.024 ) , progression‐free survival ( 44.8 % vs 79.8 % , P = 0.004 ) , and distant metastasis‐free survival ( 43.0 % vs 17.3 % , P = 0.016 ) . Multivariate regression analysis confirmed that Aurora‐A was indeed an independent prognostic factor for death , recurrence , and distant metastasis both in the testing set and overall patients . Moreover , a positive correlation between Aurora‐A and HIF‐1α was detected ( P = 0.037 ) . Importantly , although HIF‐1α did not show any prognostic effect for patient outcome , the subset with Aurora‐A and HIF‐1α co‐overexpression had the poorest overall , progression‐free , and distant metastasis‐free survival ( all P < 0.05 ) . Our results confirmed that Aurora‐A was an independent prognostic factor for NPC . Aurora‐A combined with HIF‐1α refined the risk definition of the patient subset , thus potentially directing locally advanced NPC patients for more selective therapy . ( Cancer Sci , doi : 10.1111/j.1349‐7006.2012.02332.x , 2012 OBJECTIVES Aurora A kinase ( AAK ) , a key mitotic regulator , is implicated in the pathogenesis of several tumors , including ovarian cancer . This single-arm phase II study assessed single-agent efficacy and safety of the investigational AAK inhibitor MLN8237 ( alisertib ) , in patients with platinum-refractory or -resistant epithelial ovarian , fallopian tube , or primary peritoneal carcinoma . METHODS Adult women with malignant , platinum-treated disease received MLN8237 50 mg orally twice daily for 7 days plus 14 days ' rest ( 21-day cycles ) . The primary endpoint was combined objective tumor response rate per Response Evaluation Criteria in Solid Tumors ( RECIST ) and /or CA-125 criteria . Secondary endpoints included response duration , clinical benefit rate , progression-free survival ( PFS ) , time-to-progression ( TTP ) , and safety . RESULTS Thirty-one patients with epithelial ovarian ( n=25 ) , primary peritoneal ( n=5 ) , and fallopian tube carcinomas ( n=1 ) were enrolled . Responses of 6.9 - 11.1 month duration were observed in 3 ( 10 % ) patients with platinum-resistant ovarian cancer . Sixteen ( 52 % ) patients achieved stable disease with a mean duration of response of 2.86 months and which was durable for ≥3 months in 6 ( 19 % ) . Median PFS and TTP were 1.9 months . Most common drug-related grade ≥3 adverse events were neutropenia ( 42 % ) , leukopenia ( 23 % ) , stomatitis , and thrombocytopenia ( each 19 % ) ; 6 % reported febrile neutropenia . CONCLUSIONS These data suggest that MLN8237 has modest single-agent antitumor activity and may produce responses and durable disease control in some patients with platinum-resistant ovarian cancer . MLN8237 is currently undergoing evaluation in a phase I/II trial with paclitaxel in recurrent ovarian cancer Purpose : This phase I study evaluated the safety , pharmacokinetics , pharmacodynamics , and efficacy of the investigational oral drug MLN8237 ( alisertib ) , a small-molecule Aurora A kinase ( AAK ) inhibitor , in 87 adult patients with advanced solid tumors . Experimental Design : Sequential cohorts of patients received MLN8237 5 to 150 mg orally once daily or twice daily for 7 , 14 , or 21 days , followed by 14 days ' rest per cycle . MLN8237 pharmacokinetics was characterized , and the relative bioavailability of an enteric-coated tablet ( ECT ) formulation was evaluated in reference to the original powder-in-capsule ( PIC ) formulation . Pharmacodynamic effects of MLN8237 on inhibition of AAK activity were evaluated in skin biopsies . Tolerability and response to treatment were assessed . Results : Common toxicities included fatigue , nausea , and neutropenia . Plasma exposures increased dose proportionally ( 5–150 mg/d ) , and were similar for PIC and ECT . The terminal half-life was 23 hours . At the maximum tolerated dose of 50 mg twice daily on the 7-day schedule , the mitotic index of the skin basal epithelium was increased within 24 hours after MLN8237 administration on days 1 and 7 , a finding consistent with AAK inhibition . One ( 1 % ) patient achieved a partial response lasting for more than 1 year and received MLN8237 for 51 cycles ; 20 ( 23 % ) patients achieved stable disease for ≥3 months . Conclusions : This first-in-human trial of MLN8237 showed tolerability and favorable pharmacokinetics in this patient population . The recommended phase II dose of MLN8237 is 50 mg twice daily orally for 7 days in 21-day cycles , which is being evaluated further in the treatment of various solid tumors and hematologic malignancies . Clin Cancer Res ; 18(17 ) ; 4775–84 . © 2012 AACR BACKGROUND Alisertib is an investigational , oral , selective inhibitor of aurora kinase A. We aim ed to investigate the safety and activity of single-agent alisertib in patients with predefined types of advanced solid tumours . METHODS We did a multicentre phase 1/2 study at 40 centres in four countries ( Czech Republic , France , Pol and , and the USA ) . Here , we report results from phase 2 ; enrolment for the study began on Feb 16 , 2010 , and ended on May 3 , 2013 . Adult patients were eligible for the study if they had either breast cancer , small-cell lung cancer , non-small-cell lung cancer , head and neck squamous-cell carcinoma , or gastro-oesophageal adenocarcinoma that had relapsed or was refractory to chemotherapy . Patients had to have undergone two or fewer previous cytotoxic regimens ( four or fewer for breast cancer patients ) , not including adjuvant or neoadjuvant treatments . Enrolment followed a two-stage design : to proceed to the second stage , two or more objective responses were needed in the first 20 response-assessable patients in each of the five tumour cohorts . Alisertib was administered orally in 21-day cycles at the recommended phase 2 dose of 50 mg twice daily for 7 days followed by a break of 14 days . The protocol -specified primary endpoint was the proportion of patients with an objective response , assessed by Response Evaluation Criteria In Solid Tumors version 1.1 in the response-assessable population ( ie , patients with measurable disease who received at least one dose of alisertib and had undergone at least one post-baseline tumour assessment ) . This completed trial is registered with Clinical Trials.gov , NCT01045421 . FINDINGS By May 31 , 2013 , 249 patients had been treated , 53 with breast cancer , 60 with small-cell lung cancer , 26 with non-small-cell lung cancer , 55 with head and neck squamous-cell carcinoma , and 55 with gastro-oesophageal adenocarcinoma . Among response-assessable patients , an objective response was noted in nine ( 18 % , 95 % CI 9 - 32 ) of 49 women with breast cancer , ten ( 21 % , 10 - 35 ) of 48 participants with small-cell lung cancer , one ( 4 % , 0 - 22 ) of 23 patients with non-small-cell lung cancer , four ( 9 % , 2 - 21 ) of 45 people with head and neck squamous-cell carcinoma , and four ( 9 % , 2 - 20 ) of 47 individuals with gastro-oesophageal adenocarcinoma ; all were partial responses . Adverse events were similar across tumour types . The most frequent drug-related grade 3 - 4 adverse events included neutropenia ( n=107 [ 43 % ] ) , leukopenia ( 53 [ 21 % ] ) , and anaemia ( 26 [ 10 % ] ) . Serious drug-related adverse events were reported in 108 ( 43 % ) patients . INTERPRETATION These data support further clinical assessment of alisertib in patients with solid tumours , particularly those with breast cancer and small-cell lung cancer . FUNDING Millennium Pharmaceuticals , Inc , a wholly owned subsidiary of Takeda Pharmaceutical Company Limited Output:	Our present meta- analysis indicates that the Aurora kinase A is an effective prognosticator in solid tumors patients .
MS212076	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Maternal and newborn mortality rates remain unacceptably high , especially where the majority of births occur in home setting s or in facilities with inadequate re sources . The introduction of emergency obstetric and newborn care services has been proposed by several organizations in order to improve pregnancy outcomes . However , the effectiveness of emergency obstetric and neonatal care services has never been proven . Also unproven is the effectiveness of community mobilization and community birth attendant training to improve pregnancy outcomes . Methods / Design We have developed a cluster-r and omized controlled trial to evaluate the impact of a comprehensive intervention of community mobilization , birth attendant training and improvement of quality of care in health facilities on perinatal mortality in low and middle-income countries where the majority of births take place in homes or first level care facilities . This trial will take place in 106 clusters ( 300 - 500 deliveries per year each ) across 7 sites of the Global Network for Women 's and Children 's Health Research in Argentina , Guatemala , India , Kenya , Pakistan and Zambia . The trial intervention has three key elements , community mobilization , home-based life saving skills for communities and birth attendants , and training of providers at obstetric facilities to improve quality of care . The primary outcome of the trial is perinatal mortality . Secondary outcomes include rates of stillbirth , 7-day neonatal mortality , maternal death or severe morbidity ( including obstetric fistula , eclampsia and obstetrical sepsis ) and 28-day neonatal mortality . Discussion In this trial , we are evaluating a combination of interventions including community mobilization and facility training in an attempt to improve pregnancy outcomes . If successful , the results of this trial will provide important information for policy makers and clinicians as they attempt to improve delivery services for pregnant women and newborns in low-income countries . Trial Registration Clinical Trials.gov OBJECTIVE : Changes in the ability of midwives to perform practical skills , after completion of the Maternal Care Manual of the Perinatal Education Program , were determined . STUDY DESIGN : A prospect i ve , controlled trial in a study town and two control towns . The practical skills of midwives caring for pregnant women in the towns were determined . Subsequently , the Maternal Care Manual was studied by midwives in the study town , and the skills of all midwives were subsequently evaluated . RESULTS : A total of 34 midwives in the study town and 39 midwives in the two control towns were studied . The marks showed a significant ( p ≤ 0.000 ) improvement in the study town when comparing the pre- and postintervention marks . The mean improvement in the study town was 36.6 % . DISCUSSION : The practical skills of midwives improved significantly . The Perinatal Education Program can be implemented with confidence as a distance learning program that is especially suited to the needs of health workers in remote regions The potential for traditional birth attendants ( TBAs ) to improve neonatal health outcomes has largely been overlooked during the current debate regarding the role of TBAs in improving maternal health . R and omly-selected TBAs ( n=93 ) were interviewed to gain a more thorough underst and ing of their knowledge , attitudes , and practice s regarding maternal and newborn care . Practice s , such as using a clean cord-cutting instrument ( 89 % ) and h and -washing before delivery ( 74 % ) , were common . Other beneficial practice s , such as thermal care , were low . Trained TBAs were more likely to wash h and s with soap before delivery , use a clean delivery-kit , and advise feeding colostrum . Although mustard oil massage was a universal practice , 52 % of the TBAs indicated their willingness to consider alternative oils . Low-cost , evidence -based interventions for improving neonatal outcomes might be implemented by TBAs in this setting where most births take place in the home and neonatal mortality risk is high . Continuing efforts to define the role of TBAs may benefit from an emphasis on their potential as active promoters of essential newborn care BACKGROUND Two recent trials have shown that women 's groups can reduce neonatal mortality in poor communities . We assessed the effectiveness of a scaled-up development programme with women 's groups to address maternal and neonatal care in three rural districts of Bangladesh . METHODS 18 clusters ( with a mean population of 27 953 [ SD 5953 ] ) in three districts were r and omly assigned to either intervention or control ( nine clusters each ) by use of stratified r and omisation . For each district , cluster names were written on pieces of paper , which were folded and placed in a bottle . The first three cluster names drawn from the bottle were allocated to the intervention group and the remaining three to control . All clusters received health services strengthening and basic training of traditional birth attendants . In intervention clusters , a facilitator convened 18 groups every month to support participatory action and learning for women , and to develop and implement strategies to address maternal and neonatal health problems . Women were eligible to participate if they were aged 15 - 49 years , residing in the project area , and had given birth during the study period ( Feb 1 , 2005 , to Dec 31 , 2007 ) . Neither study investigators nor participants were masked to treatment assignment . In a population of 229 195 people ( intervention clusters only ) , 162 women 's groups provided coverage of one group per 1414 population . The primary outcome was neonatal mortality rate ( NMR ) . Analysis was by intention to treat . This trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N54792066 . FINDINGS We monitored outcomes for 36 113 births ( intervention clusters , n=17 514 ; control clusters , n=18 599 ) in a population of 503 163 over 3 years . From 2005 to 2007 , there were 570 neonatal deaths in the intervention clusters and 656 in the control clusters . Cluster-level mean NMR ( adjusted for stratification and clustering ) was 33.9 deaths per 1000 livebirths in the intervention clusters compared with 36.5 per 1000 in the control clusters ( risk ratio 0.93 , 95 % CI 0.80 - 1.09 ) . INTERPRETATION For participatory women 's groups to have a significant effect on neonatal mortality in rural Bangladesh , detailed attention to programme design and context ual factors , enhanced population coverage , and increased enrolment of newly pregnant women might be needed . FUNDING Women and Children First , the UK Big Lottery Fund , Saving Newborn Lives , and the UK Department for International Development We compared the effects of lecture-style ( L ) and interactive problem-based ( I ) educational programs on knowledge , attitude , and practice s ( KAP ) of traditional birth attendants in the Philippines . Participants in two cities were r and omized to L and I teaching groups and completed a question naire pre- , immediately post- , and 6 months after education . Mothers reported practice s of the attendants . There was significant improvement in mean knowledge scores ( L 16.8 to 17.9 and I 16.4 to 19.3 ) in group I. Group I scores continued to improve 6 months later . Attitude scores significantly improved in both groups and decreased 6 months later , indicating a need for reinforcement . Certain undesirable practice s such as late cord clamping and holding the baby upside down following birth were changed in both groups . Actual practice s reported by mothers were carried out less frequently than indicated by providers , indicating a need for further education and possibly provision of adequate re sources . Interactive ( I ) learning is a preferred method for education of traditional birth attendants Background Birth attendance by trained health workers is low in rural Nepal . Local participation in improving health services and increased interaction between health systems and communities may stimulate dem and for health services . Significant increases in birth attendance by trained health workers may be affected through community mobilisation by local women 's groups and health management committee strengthening . We will test the effect of community mobilisation through women 's groups , and health management committee strengthening , on institutional deliveries and home deliveries attended by trained health workers in Makwanpur District . Design Cluster r and omised controlled trial involving 43 village development committee clusters . 21 clusters will receive the intervention and 22 clusters will serve as control areas . In intervention areas , Female Community Health Volunteers are supported in convening monthly women 's groups . The groups work through an action research cycle in which they consider barriers to institutional delivery , plan and implement strategies to address these barriers with their communities , and evaluate their progress . Health management committees participate in three-day workshops that use appreciative inquiry methods to explore and plan ways to improve maternal and newborn health services . Follow-up meetings are conducted every three months to review progress . Primary outcomes are institutional deliveries and home deliveries conducted by trained health workers . Secondary outcome measures include uptake of antenatal and postnatal care , neonatal mortality and stillbirth rates , and maternal morbidity . Trial registration numberIS RCT BACKGROUND Newborn deaths account for 57 % of deaths in children younger than 5 years in Pakistan . Although a large programme of trained lady health workers ( LHWs ) exists , the effectiveness of this training on newborn outcomes has not been studied . We aim ed to evaluate the effectiveness of a community-based intervention package , principally delivered through LHWs working with traditional birth attendants and community health committees , for reduction of perinatal and neonatal mortality in a rural district of Pakistan . METHODS We undertook a cluster r and omised trial between February , 2006 , and March , 2008 , in Hala and Matiari subdistricts , Pakistan . Catchment areas of primary care facilities and all affiliated LHWs were used to define clusters , which were allocated to intervention and control groups by restricted , stratified r and omisation . The intervention package delivered by LHWs through group sessions consisted of promotion of antenatal care and maternal health education , use of clean delivery kits , facility births , immediate newborn care , identification of danger signs , and promotion of careseeking ; control clusters received routine care . Independent data collectors undertook quarterly household surveillance to capture data for births , deaths , and household practice s related to maternal and newborn care . Data collectors were masked to cluster allocation ; those analysing data were not . The primary outcome was perinatal and all-cause neonatal mortality . Analysis was by intention to treat . This trial is registered , IS RCT N16247511 . FINDINGS 16 clusters were assigned to intervention ( 23,353 households , 12,391 total births ) and control groups ( 23,768 households , 11,443 total births ) . LHWs in the intervention clusters were able to undertake 4428 ( 63 % ) of 7084 planned group sessions , but were only able to visit 2943 neonates ( 24 % ) of a total 12,028 livebirths in their catchment villages . Stillbirths were reduced in intervention clusters ( 39·1 stillbirths per 1000 total births ) compared with control ( 48·7 per 1000 ; risk ratio [ RR ] 0·79 , 95 % CI 0·68 - 0·92 ; p=0·006 ) . The neonatal mortality rate was 43·0 deaths per 1000 livebirths in intervention clusters compared with 49·1 per 1000 in control groups ( RR 0·85 , 0·76 - 0·96 ; p=0·02 ) . INTERPRETATION Our results support the scale-up of preventive and promotive maternal and newborn interventions through community health workers and emphasise the need for attention to issues of programme management and coverage for such initiatives to achieve maximum potential . FUNDING WHO ; Saving Newborn Lives Program of Save the Children USA , funded by the Bill & Melinda Gates Foundation OBJECTIVES In a community r and omized trial , we aim ed to promote exclusive breastfeeding and appropriate complementary feeding practice s in under-twos to ascertain the feasibility of using available channels for nutrition counselling , their relative performance and the relationship between intensity of counselling and behaviour change . We also assessed whether using multiple opportunities to impart nutrition education adversely affected routine activities . METHODS We conducted a community r and omized , controlled effectiveness trial in rural Haryana , India , with four intervention and four control communities . We trained health and nutrition workers in the intervention communities to counsel mothers at multiple contacts on breastfeeding exclusively for 6 months and on appropriate complementary feeding practice s thereafter . The intervention was not just training health and nutrition workers in counselling but included community and health worker mobilization . FINDINGS In the intervention group , about 32 % of caregivers were counselled by traditional birth attendants at birth . The most frequent sources of counselling from birth to 3 months were immunization sessions ( 45.1 % ) and home visits ( 32.1 % ) , followed closely by weighing sessions ( 25.5 % ) ; from 7 to 12 months , home visits ( 42.6 % ) became more important than the other two . An increase in the number of channels through which caregivers were counselled was positively associated with exclusive breastfeeding prevalence at 3 months ( p = 0.002 ) , consumption of milk/cereal gruel or mix use at 9 months ( p = 0.004 ) and 18 months ( p = 0.003 ) , undiluted milk at 9 months ( p<0.0001 ) and 24 hour non-breast-milk energy intakes at 18 months ( p = 0.023 ) , after controlling for potential confounding factors . Intervention areas , compared with the control , had higher coverage for vitamin A ( 45 % vs. 11.5 % ) and iron folic acid ( 45 % vs. 0.4 % ) supplementation . CONCLUSIONS Using multiple available opportunities and workers for counselling caregivers was feas Output:	The results are promising for some outcomes ( perinatal death , stillbirth and neonatal death ) . A lack of contrast in training in the intervention and control clusters may have contributed to the null result for stillbirths and an insufficient number of studies may have contributed to the failure to achieve significance for early neonatal deaths . Despite the additional studies included in this up date d systematic review , there remains insufficient evidence to establish the potential of TBA training to improve peri-neonatal mortality
MS212077	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Adherence and accuracy of self-monitoring of dietary intake influences success in weight management interventions . Information technologies such as computers and smartphones have the potential to improve adherence and accuracy by reducing the burden associated with monitoring dietary intake using traditional paper-based food records . We evaluated the acceptability and accuracy of three different 7-day food record methods ( online accessed via computer , online accessed via smartphone , and paper-based ) . Young women ( N=18 ; aged 23.4±2.9 years ; body mass index 24.0±2.2 ) completed the three 7-day food records in r and om order with 7-day washout periods between each method . Total energy expenditure ( TEE ) was derived from resting energy expenditure ( REE ) measured by indirect calorimetry and physical activity level ( PAL ) derived from accelerometers ( TEE = REE × PAL ) . Accuracy of the three methods was assessed by calculating absolute ( energy intake [EI]-TEE ) and percentage difference ( EI/TEE × 100 ) between self-reported EI and TEE . Acceptability was assessed via question naire . Mean±st and ard deviation TEE was 2,185±302 kcal/day and EI was 1,729±249 kcal/day , 1,675±287kcal/day , and 1,682±352 kcal/day for computer , smartphone , and paper records , respectively . There were no significant differences between absolute and percentage differences between EI and TEE for the three methods : computer , -510±389 kcal/day ( 78 % ) ; smartphone , -456±372 kcal/day ( 80 % ) ; and paper , -503±513 kcal/day ( 79 % ) . Half of participants ( n=9 ) preferred computer recording , 44.4 % preferred smartphone , and 5.6 % preferred paper-based records . Most participants ( 89 % ) least preferred the paper-based record . Because online food records completed on either computer or smartphone were as accurate as paper-based records but more acceptable to young women , they should be considered when self-monitoring of intake is recommended to young women Introduction Electronic self-monitoring of affective symptoms using cell phones is suggested as a practical and inexpensive way to monitor illness activity and identify early signs of affective symptoms . It has never been tested in a r and omised clinical trial whether electronic self-monitoring improves outcomes in bipolar disorder . We are conducting a trial testing the effect of using a Smartphone for self-monitoring in bipolar disorder . Methods We developed the MONARCA application for And roid-based Smartphones , allowing patients suffering from bipolar disorder to do daily self-monitoring — including an interactive feedback loop between patients and clinicians through a web-based interface . The effect of the application was tested in a parallel-group , single-blind r and omised controlled trial so far including 78 patients suffering from bipolar disorder in the age group 18–60 years who were given the use of a Smartphone with the MONARCA application ( intervention group ) or to the use of a cell phone without the application ( placebo group ) during a 6-month study period . The study was carried out from September 2011 . The outcomes were changes in affective symptoms ( primary ) , social functioning , perceived stress , self-rated depressive and manic symptoms , quality of life , adherence to medication , stress and cognitive functioning ( secondary and tertiary ) . Analysis Recruitment is ongoing . Ethics Ethical permission has been obtained . Dissemination Positive , neutral and negative findings of the study will be published . Registration details The trial is approved by the Regional Ethics Committee in The Capital Region of Denmark ( H-2 - 2011 - 056 ) and The Danish Data Protection Agency ( 2013 - 41 - 1710 ) . The trial is registered at Clinical Trials.gov as NCT01446406 Background Refugees experience multiple health and social needs . This requires an integrated approach to care in the countries of resettlement , including Canada . Perhaps , interactive eHealth tools could build bridges between medical and social care in a timely manner . The authors developed and piloted a multi-risk Computer-assisted Psychosocial Risk Assessment ( CaPRA ) tool for Afghan refugees visiting a community health center . The iPad based CaPRA survey was completed by the patients in their own language before seeing the medical practitioner . The computer then generated individualized feedback for the patient and provider with suggestions about available services . Methods A pilot r and omized trial was conducted with adult Afghan refugees who could read Dari/Farsi or English language . Consenting patients were r and omly assigned to the CaPRA ( intervention ) or usual care ( control ) group . All patients completed a paper-pencil exit survey . The primary outcome was patient intention to see a psychosocial counselor . The secondary outcomes were patient acceptance of the tool and visit satisfaction . Results Out of 199 approached patients , 64 were eligible and 50 consented and one withdrew ( CaPRA = 25 ; usual care = 24 ) . On average , participants were 37.6 years of age and had lived 3.4 years in Canada . Seventy-two percent of participants in CaPRA group had intention to visit a psychosocial counselor , compared to 46 % in usual care group [ X2 (1)=3.47 , p = 0.06 ] . On a 5-point scale , CaPRA group participants agreed with the benefits of the tool ( mean = 4 ) and were ‘ unsure ’ about possible barriers to interact with the clinicians ( mean = 2.8 ) or to privacy of information ( mean = 2.8 ) in CaPRA mediated visits . On a 5-point scale , the two groups were alike in patient satisfaction ( mean = 4.3 ) . Conclusion The studied eHealth tool offers a promising model to integrate medical and social care to address the health and settlement needs of refugees . The tool ’s potential is discussed in relation to implication s for healthcare practice . The study should be replicated with a larger sample to generalize the results while controlling for potential confounders Background The electronic self report assessment - cancer ( ESRA-C ) , has been shown to reduce symptom distress during cancer therapy The purpose of this analysis was to evaluate aspects of how the ESRA-C intervention may have result ed in lower symptom distress ( SD ) . Methods Patients at two cancer centers were r and omized to ESRA-C assessment only ( control ) or the Web-based ESRA-C intervention delivered to patients ’ homes or to a tablet in clinic . The intervention allowed patients to self-monitor symptom and quality of life ( SxQOL ) between visits , receive self-care education and coaching to report SxQOL to clinicians . Summaries of assessment s were delivered to clinicians in both groups . Audio-recordings of clinic visits made 6 weeks after treatment initiation were coded for discussion s of 26 SxQOL issues , focusing on patients ’ /caregivers ’ coached verbal reports of SxQOL severity , pattern , alleviating/aggravating factors and requests for help . Among issues identified as problematic , two measures were defined for each patient : the percent SxQOL reported that included a coached statement , and an index of verbalized coached statements per SxQOL . The Wilcoxon rank test was used to compare measures between groups . Clinician responses to problematic SxQOL were compared . A mediation analysis was conducted , exploring the effect of verbal reports on SD outcomes . Results 517 ( 256 intervention ) clinic visits were audio-recorded . General discussion of problematic SxQOL was similar in both groups . Control group patients reported a median 75 % of problematic SxQOL using any specific coached statement compared to a median 85 % in the intervention group ( p = .0009 ) . The median report index of coached statements was 0.25 for the control group and 0.31 for the intervention group ( p = 0.008 ) . Fatigue , pain and physical function issues were reported significantly more often in the intervention group ( all p < .05 ) . Clinicians ' verbalized responses did not differ between groups . Patients ' verbal reports did not mediate final SD outcomes ( p = .41 ) . Conclusions Adding electronically-delivered , self-care instructions and communication coaching to ESRA-C promoted specific patient descriptions of problematic SxQOL issues compared with ESRA-C assessment alone . However , clinician verbal responses were no different and subsequent symptom distress group differences were not mediated by the patients ' reports . Trial registration NCT00852852 ; 26 Feb Purpose To test the impact of method of administration ( MOA ) on the measurement characteristics of items developed in the Patient-Reported Outcomes Measurement Information System ( PROMIS ) . Methods Two non-overlapping parallel 8-item forms from each of three PROMIS domains ( physical function , fatigue , and depression ) were completed by 923 adults ( age 18–89 ) with chronic obstructive pulmonary disease , depression , or rheumatoid arthritis . In a r and omized cross-over design , subjects answered one form by interactive voice response ( IVR ) technology , paper question naire ( PQ ) , personal digital assistant ( PDA ) , or personal computer ( PC ) on the Internet , and a second form by PC , in the same administration . Structural invariance , equivalence of item responses , and measurement precision were evaluated using confirmatory factor analysis and item response theory methods . Results Multigroup confirmatory factor analysis supported equivalence of factor structure across MOA . Analyses by item response theory found no differences in item location parameters and strongly supported the equivalence of scores across MOA . Conclusions We found no statistically or clinical ly significant differences in score levels in IVR , PQ , or PDA administration as compared to PC . Availability of large item response theory-calibrated PROMIS item banks allowed for innovations in study design and analysis Background Compared to females , males experience higher rates of chronic disease and mortality , yet few health promotion initiatives are specifically aim ed at men . Therefore , the aim of the ManUp Study is to examine the effectiveness of an IT-based intervention to increase the physical activity and nutrition behaviour and literacy in middle-aged males ( aged 35–54 years ) . Method / Design The study design was a two-arm r and omised controlled trial , having an IT-based ( applying website and mobile phones ) and a print-based intervention arm , to deliver intervention material s and to promote self-monitoring of physical activity and nutrition behaviours . Participants ( n = 317 ) were r and omised on a 2:1 ratio in favour of the IT-based intervention arm . Both intervention arms completed assessment s at baseline , 3 , and 9 months . All participants completed self-report assessment s of physical activity , sitting time , nutrition behaviours , physical activity and nutrition literacy , perceived health status and socio-demographic characteristics . A r and omly selected sub- sample in the IT-based ( n = 61 ) and print-based ( n = 30 ) intervention arms completed objective measures of height , weight , waist circumference , and physical activity as measured by accelerometer ( Actigraph GT3X ) . The average age of participants in the IT-based and print-based intervention arm was 44.2 and 43.8 years respectively . The majority of participants were employed in professional occupations ( IT-based 57.6 % , Print-based 54.2 % ) and were overweight or obese ( IT-based 90.8 % , Print-based 87.3 % ) . At baseline a lower proportion of participants in the IT-based ( 70.2 % ) group agreed that 30 minutes of physical activity each day is enough to improve health compared to the print-based ( 82.3 % ) group ( p = .026 ) . The IT-based group consumed a significantly lower number of serves of red meat in the previous week , compared to the print-based group ( p = .017 ) . No other significant between-group differences were observed at baseline . Discussion The ManUp Study will examine the effectiveness of an IT-based approach to improve physical activity and nutrition behaviour and literacy . Study outcomes will provide much needed information on the efficacy of this approach in middle aged males , which is important due to the large proportions of males at risk , and the potential reach of IT-based interventions .Trial registration BACKGROUND AND PURPOSE Epi Data and Epi Info are often used together by public health agencies around the world , particularly in developing countries , to meet their needs of low-cost public health data management ; however , the current open source data management technology lacks a mobile component to meet the needs of mobile public health data collectors . The goal of this project is to explore the opportunity of filling this gap through developing and trial of a personal digital assistant ( PDA ) based data collection /entry system . It evaluated whether such a system could increase efficiency and reduce data transcription errors for public surveillance data collection in developing countries represented by Fiji . METHODS A generic PDA-based data collection software eSTEPS was developed . The software and the data collected using it directly interfaces with Epi Data . A field trial was conducted to test the viability of public health surveillance data collection using eSTEPS . The design was a r and omised , controlled trial with cross-over design . 120 participants recruited from the Fiji School of Medicine were r and omly assigned to be interviewed by one of six interviewers in one of the two ways : ( 1 ) paper-based survey followed by PDA survey and ( 2 ) PDA survey followed by paper-based survey . Data quality was measured by error rates ( logical range errors/inconsistencies , skip errors , missing values , date or time field errors and incorrect data type ) . Work flow and cost were evaluated in three stages of the survey process : ( 1 ) preparation of data collection instrument , ( 2 ) data collection and ( 3 ) data entry , validation and cleaning . User acceptance was also evaluated in the two groups of participants : ( 1 ) data collectors and ( 2 ) survey participants . RESULTS None of the errors presented in 20.8 % of the paper question naires was found in the data set collected using PDA . Sixty-two percent of the participants perceived that the PDA-based question naire took less time to complete . Data entry , validation and cleaning for the PDA- Output:	MAIN RESULTS We included 14 studies ( 15 records ) with a total of 2275 participants ; although we included only 2272 participants in the final analyses as there were missing data for three participants from one included study .Regarding data equivalence , in both controlled and uncontrolled setting s , the included studies found no significant differences in the mean overall scores between apps and other delivery modes , and that all correlation coefficients exceeded the recommended thresholds for data equivalence . Regarding adherence to the sampling protocol , apps may be better than paper but no different from SMS . We identified multiple definitions of acceptability to respondents , with inconclusive results : preference ; ease of use ; willingness to use a delivery mode ; satisfaction ; effectiveness of the system informativeness ; perceived time taken to complete the survey question naire ; perceived benefit of a delivery mode ; perceived usefulness of a delivery mode ; perceived ability to complete a survey question naire ; maximum length of time that participants would be willing to use a delivery mode ; and reactivity to the delivery mode and its successful integration into respondents ' daily routine . Our results , based on a narrative synthesis of the evidence , suggest that apps might not affect data equivalence as long as the intended clinical application of the survey question naire , its intended frequency of administration and the setting in which it was vali date d remain unchanged .
MS212078	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The coronary artery calcium ( CAC ) score is a readily and widely available tool for the noninvasive diagnosis of atherosclerotic coronary artery disease ( CAD ) . The aim of this study was to investigate the added value of the CAC score as an adjunct to gated SPECT for the assessment of CAD in an intermediate-risk population . Methods : Seventy-seven prospect ively recruited patients with intermediate risk ( as determined by the Framingham Heart Study 10-y CAD risk score ) and referred for coronary angiography because of suspected CAD underwent stress 99mTc-tetrofosmin SPECT myocardial perfusion imaging ( MPI ) and CT CAC scoring within 2 wk before coronary angiography . The sensitivity and specificity of SPECT alone and of the combination of the 2 methods ( SPECT plus CAC score ) in demonstrating significant CAD ( ≥50 % stenosis on coronary angiography ) were compared . Results : Forty-two ( 55 % ) of the 77 patients had CAD on coronary angiography , and 35 ( 45 % ) had abnormal SPECT results . The CAC score was significantly higher in subjects with perfusion abnormalities than in those who had normal SPECT results ( 889 ± 836 [ mean ± SD ] vs. 286 ± 335 ; P < 0.0001 ) . Similarly , with rising CAC scores , a larger percentage of patients had CAD . Receiver-operating-characteristic analysis showed that a CAC score of greater than or equal to 709 was the optimal cutoff for detecting CAD missed by SPECT . SPECT alone had a sensitivity and a specificity for the detection of significant CAD of 76 % and 91 % , respectively . Combining SPECT with the CAC score ( at a cutoff of 709 ) improved the sensitivity of SPECT ( from 76 % to 86 % ) for the detection of CAD , in association with a nonsignificant decrease in specificity ( from 91 % to 86 % ) . Conclusion : The CAC score may offer incremental diagnostic information over SPECT data for identifying patients with significant CAD and negative MPI results UNLABELLED In July 2009 , the Medical Advisory Secretariat ( MAS ) began work on Non-Invasive Cardiac Imaging Technologies for the Diagnosis of Coronary Artery Disease ( CAD ) , an evidence -based review of the literature surrounding different cardiac imaging modalities to ensure that appropriate technologies are accessed by patients suspected of having CAD . This project came about when the Health Services Branch at the Ministry of Health and Long-Term Care asked MAS to provide an evidentiary platform on effectiveness and cost-effectiveness of non-invasive cardiac imaging modalities . After an initial review of the strategy and consultation with experts , MAS identified five key non-invasive cardiac imaging technologies for the diagnosis of CAD . Evidence -based analyses have been prepared for each of these five imaging modalities : cardiac magnetic resonance imaging , single photon emission computed tomography , 64-slice computed tomographic angiography , stress echocardiography , and stress echocardiography with contrast . For each technology , an economic analysis was also completed ( where appropriate ) . A summary decision analytic model was then developed to encapsulate the data from each of these reports ( available on the OHTAC and MAS website).The Non-Invasive Cardiac Imaging Technologies for the Diagnosis of Coronary Artery Disease series is made up of the following reports , which can be publicly accessed at the MAS website at : www.health.gov.on.ca/mas or at www.health.gov.on.ca/english/providers/program/mas/mas_about.htmlSINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY FOR THE DIAGNOSIS OF CORONARY ARTERY DISEASE : An Evidence -Based Analysis STRESS ECHOCARDIOGRAPHY FOR THE DIAGNOSIS OF CORONARY ARTERY DISEASE : An Evidence -Based Analysis STRESS ECHOCARDIOGRAPHY WITH CONTRAST FOR THE DIAGNOSIS OF CORONARY ARTERY DISEASE : An Evidence -Based Analysis 64-Slice Computed Tomographic Angiography for the Diagnosis of Coronary Artery Disease : An Evidence -Based Analysis CARDIAC MAGNETIC RESONANCE IMAGING FOR THE DIAGNOSIS OF CORONARY ARTERY DISEASE : An Evidence -Based Analysis Pease note that two related evidence -based analyses of non-invasive cardiac imaging technologies for the assessment of myocardial viability are also available on the MAS website : POSITRON EMISSION TOMOGRAPHY FOR THE ASSESSMENT OF MYOCARDIAL VIABILITY : An Evidence -Based Analysis MAGNETIC RESONANCE IMAGING FOR THE ASSESSMENT OF MYOCARDIAL VIABILITY : an Evidence -Based Analysis The Toronto Health Economics and Technology Assessment Collaborative has also produced an associated economic report entitled : The Relative Cost-effectiveness of Five Non-invasive Cardiac Imaging Technologies for Diagnosing Coronary Artery Disease in Ontario [ Internet ] . Available from : http://theta.utoronto.ca/reports/?id=7 OBJECTIVE The objective of the analysis is to determine the diagnostic accuracy of single photon emission tomography ( SPECT ) in the diagnosis of coronary artery disease ( CAD ) compared to the reference st and ard of coronary angiography ( CA ) . The analysis is primarily meant to allow for indirect comparisons between non-invasive strategies for the diagnosis of CAD , using CA as a reference st and ard . SPECT : Cardiac SPECT , or myocardial perfusion scintigraphy ( MPS ) , is a widely used nuclear , non-invasive image acquisition technique for investigating ischemic heart disease . SPECT is currently appropriate for all aspects of detecting and managing ischemic heart disease including diagnosis , risk assessment /stratification , assessment of myocardial viability , and the evaluation of left ventricular function . Myocardial perfusion scintigraphy was originally developed as a two-dimensional planar imaging technique , but SPECT acquisition has since become the clinical st and ard in current practice . Cardiac SPECT for the diagnosis of CAD uses an intravenously administered radiopharmaceutical tracer to evaluate regional coronary blood flow usually at rest and after stress . The radioactive tracers thallium ( 201Tl ) or technetium-99 m ( 99mTc ) , or both , may be used to visualize the SPECT acquisition . Exercise or a pharmacologic agent is used to achieve stress . After the administration of the tracer , its distribution within the myocardium ( which is dependent on myocardial blood flow ) is imaged using a gamma camera . In SPECT imaging , the gamma camera rotates around the patients for 10 to 20 minutes so that multiple two-dimensional projections are acquired from various angles . The raw data are then processed using computational algorithms to obtain three-dimensional tomographic images . Since its inception , SPECT has evolved and its techniques/applications have become increasingly more complex and numerous . Accordingly , new techniques such as attenuation correction and ECG gating have been developed to correct for attenuation due to motion or soft-tissue artifact and to improve overall image clarity . RESEARCH QUESTIONS What is the diagnostic accuracy of SPECT for the diagnosis of CAD compared to the reference st and ard of CA?Is SPECT cost-effective compared to other non-invasive cardiac imaging modalities for the diagnosis of CAD?What are the major safety concerns with SPECT when used for the diagnosis of CAD ? METHODS A preliminary literature search was performed across OVID MEDLINE , MEDLINE In-Process and Other Non-Indexed Citations , EMBASE , the Cochrane Library , and the International Agency for Health Technology Assessment ( INAHTA ) for all systematic review s/meta- analysis published between January 1 , 2004 and August 22 , 2009 . A comprehensive systematic review was identified from this search and used as a basis for an up date d search . A second comprehensive literature search was then performed on October 30 , 2009 across the same data bases for studies published between January 1 , 2002 and October 30 , 2009 . Abstract s were review ed by a single review er and , for those studies meeting the eligibility criteria , full-text articles were obtained . Reference lists were also h and - search ed for any additional studies . Inclusion Criteria Exclusion Criteria Systematic review s , meta-analyses , controlled clinical trials , and observational studies Minimum sample size of 20 patients who completed coronary angiographyUse of CA as a reference st and ard for the diagnosis of CAD Data available to calculate true positives ( TP ) , false positives ( FP ) , false negatives ( FN ) and true negatives (TN)Accuracy data reported by patient not by segmentEnglish language Non- systematic review s , case reportsGrey literature and abstract sTrials using planar imaging onlyTrials conducted in patients with non-ischemic heart disease Studies done exclusively in special population s ( e.g. , patients with left branch bundle block , diabetics , minority population s ) unless insufficient data available SUMMARY OF FINDINGS Eighty-four observational studies , one non-r and omized , single arm controlled clinical trial , and one poorly reported trial that appeared to be a r and omized controlled trial ( RCT ) met the inclusion criteria for this review . All studies assessed the diagnostic accuracy of myocardial perfusion SPECT for the diagnosis of CAD using CA as a reference st and ard . Based on the results of these studies the following conclusions were made : According to very low quality evidence , the addition of attenuation correction to traditional or ECG-gated SPECT greatly improves the specificity of SPECT for the diagnosis of CAD although this improvement is not statistically significant . A trend towards improvement of specificity was also observed with the addition of ECG gating to traditional SPECT.According to very low quality evidence , neither the choice of stress agent ( exercise or pharmacologic ) nor the choice of radioactive tracer ( technetium vs. thallium ) significantly affect the diagnostic accuracy of SPECT for the diagnosis of CAD although a trend towards accuracy improvement was observed with the use of pharmacologic stress over exercise stress and technetium over thallium . Considerably heterogeneity was observed both within and between trials . This heterogeneity may explain why some of the differences observed between accuracy estimates for various subgroups were not statistically significant . More complex analytic techniques such as meta-regression may help to better underst and which study characteristics significantly influence the diagnostic accuracy of SPECT Background Although single photon emission computed tomography ( SPECT ) and positron emission tomography ( PET ) myocardial perfusion imaging ( MPI ) have evolved considerably over the last decade , there is no recent comparison of diagnostic performance . This study was design ed to assess relative image quality , interpretive confidence , and diagnostic accuracy by use of contemporary technology and protocol s. Methods and Results By consensus and without clinical information , 4 experienced nuclear cardiologists interpreted 112 SPECT technetium-99 m sestamibi and 112 PET rubidium-82 MPI electrocardiography (ECG)-gated rest/pharmacologic stress studies in patient population s matched by gender , body mass index , and presence and extent of coronary disease . The patients were categorized as having a low likelihood for coronary artery disease ( 27 in each group ) or had coronary angiography within 60 days . SPECT scans were acquired on a Cardio-60 system and PET scans on an ECAT ACCEL scanner . Image quality was excellent for 78 % and 79 % of rest and stress PET scans , respectively , versus 62 % and 62 % of respective SPECT scans ( both p < .05 ) . An equal percent of PET and SPECT gated images were rated excellent in quality . Interpretations were definitely normal or abnormal for 96 % of PET scans versus 81 % of SPECT scans ( p = .001 ) . Diagnostic accuracy was higher for PET for both stenosis severity thresholds of 70 % ( 89 % vs 79%,p = .03 ) and 50 % ( 87 % vs 71%,p = .003 ) and was higher in men and women , in obese and nonobese patients , and for correct identification of multivessel coronary artery disease . Conclusion In a large population of matched pharmacologic stress patients , myocardial perfusion PET was superior to SPECT in image quality , interpretive certainty , and diagnostic accuracy BACKGROUND The present study compared computed tomographic coronary angiography ( CTA ) and positron emission tomography ( PET ) for the detection of significant anatomical coronary artery stenosis as defined by conventional invasive coronary angiography ( CICA ) . METHODS The study protocol was approved by the local ethics board , and informed consent was obtained from all patients . Of the 26 patients ( mean age 57+/-9 years , 18 men ) who prospect ively underwent CTA and rubidium-82 PET before CICA , 24 patients had a history of chest pain . Images were interpreted by expert readers and assessed for the presence of anatomically significant coronary stenosis ( 50 % luminal diameter stenosis or greater ) or myocardial perfusion defects . Diagnostic test characteristics were analyzed using patient-based , territory-based , vessel-based and segment-based analyses . RESULTS In the 24 patients referred for chest pain , CTA had similar sensitivity to PET , but was more specific ( sensitivity 95 % [ 95 % CI 72 % to 100 % ] versus 95 % [ 95 % CI 72 % to 100 % ] , respectively ; specificity 100 % [ 95 % CI 46 % to 100 % ] versus 6 Output:	Rb-82 PET is accurate for the detection of obstructive CAD and , despite advances in SPECT technology , remains superior . More widespread use of Rb-82 PET may be beneficial to improve CAD detection
MS212079	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE The aim of this study was to compare perinatal outcomes of patients with second-trimester ultrasonographic evidence of preterm dilatation of the internal os treated with cerclage versus those of patients not treated with cerclage . STUDY DESIGN From May 1998 through June 1999 patients with ultrasonographic evidence of preterm dilatation of the internal os between 16 and 24 weeks ' gestation were r and omly assigned to receive a McDonald cerclage or no cerclage . Before r and om assignment all patients underwent amniocentesis and urogenital cultures and then received 48 hours of therapy with indomethacin and antibiotics . After treatment each patient was followed up as an outpatient with bed rest and weekly ultrasonographic evaluation . RESULTS Of the 61 patients 31 were r and omly assigned to cerclage and 30 were r and omly assigned to no cerclage . There were no differences between groups with respect to maternal demographic characteristics , risk factors for preterm birth , cervical measurements , rescue procedures , readmission , chorioamnionitis , and abruptio placentae . The mean gestational age at delivery ( 33.5 + /- 6.3 weeks ) and the perinatal death rate ( 12 . 9 % ) in the cerclage group were similar to the mean gestational age at delivery ( 34.7 + /- 4.7 weeks ; P = .4 ) and the perinatal death rate ( 10.0 % ; P = .9 ) in the no-cerclage group . CONCLUSION Treatment with McDonald cerclage of preterm dilatation of the cervix detected ultrasonographically during the second trimester did not improve perinatal outcomes OBJECTIVE Our purpose was to compare the accuracy of ultrasonographic and manual cervical examinations for the prediction of preterm delivery . STUDY DESIGN One hundred two singleton pregnancies at high risk for preterm delivery were followed up prospect ively from 14 to 30 weeks with both serial cervical ultrasonography measurements and manual examinations of the length of the cervix . The primary outcome studied was preterm ( < 35 weeks ) delivery . RESULTS Excluding six induced preterm deliveries , 96 pregnancies were analyzed . The mean cervical length measured by ultrasonography was 20.6 mm in pregnancies delivered preterm ( n = 17 ) and 31.3 mm in pregnancies delivered at term ( n = 79 ) ( p = 0.003 ) ; the mean cervical lengths measured by manual examination were 16.1 mm and 18.6 mm in the same preterm and term pregnancies , respectively ( not significant ) . The sixteenth- and twentieth-week ultrasonographic cervical lengths predicted preterm delivery most accurately ( p < 0.0005 ) . The 25th percentiles of ultrasonographic ( 25 mm ) and manual ( 16 mm ) cervical lengths showed relative risks for preterm delivery of 4.8 ( 95 % confidence interval 2.1 to 11.1 , p = 0.0004 ) and 2.0 ( 95 % confidence interval 0.5 to 4.7 , p = 0.1 ) , respectively ; sensitivity , specificity , and positive and negative predictive values were 59 % , 85 % , 45 % , 91 % , and 41 % , 77 % , 28 % , and 86 % , respectively . CONCLUSION Cervical length measured by ultrasonography is a better predictor of preterm delivery than is cervical length measured by manual examination . Cervical ultrasonography in patients at high risk for preterm birth seems to be most predictive of preterm delivery when it is performed between 14 and 22 weeks ' gestation OBJECTIVE To compare cervical length measurements obtained at 11 to 14 weeks and 22 to 24 weeks of gestation in an unselected group of pregnant women and to correlate the measurements with time of delivery . METHODS This was a prospect i ve study involving 529 pregnant women attending for routine antenatal care who underwent transvaginal scans at 11 - 14 weeks and 22 - 24 weeks for evaluation of cervical length . The mean cervical length was calculated at both stages of gestation and lengths were compared between groups which delivered at term or prematurely , this being defined as delivery before 37 completed weeks of gestation . RESULTS The mean cervical lengths at 11 - 14 and 22 - 24 weeks were , respectively , 42.4 mm and 38.6 mm . Cervical length at 11 - 14 weeks was not significantly different between the groups which delivered at term ( 42.7 mm ) and preterm ( 40.6 mm ) . However , at the 22 - 24-week evaluation , cervical length was significantly shorter in the group which had a preterm delivery than in that which had a term delivery ( 26.7 mm and 39.3 mm , respectively ; P = 0.0001 ) . In the group of women with a previous history of one or more preterm deliveries , there was a greater shortening in cervical length from the first to the second evaluation than there was in the group of women with no previous history of preterm delivery . This shortening was also more pronounced in the group which delivered prematurely ( from 40.6 mm to 26.7 mm ) than in that which delivered at term ( from 42.7 mm to 39.3 mm ) . CONCLUSION There is a spontaneous shortening in the pregnant cervix from the first to the second trimester of pregnancy . The shortening is more rapid in pregnant women who deliver prematurely and who have a history of previous preterm delivery BACKGROUND Measurement of mid-gestation cervix length has become a common screening tool for preterm birth . Our study was design ed to assess the value of cervix length and serum relaxin in the prediction of spontaneous preterm birth at < 35 and < 37 weeks ' gestation in a general obstetric population . METHODS A prospect i ve cohort of women with a singleton pregnancy had blood collected at 24 and 28 weeks ' gestation for determination of serum relaxin immediately before transvaginal ultrasound measurement of cervical length . Patients and referring physicians were blinded to cervix length and relaxin levels to preclude changes in management . The primary outcomes were spontaneous delivery at < 35 and < 37 weeks ' gestation . RESULTS A total of 1004 women entered the study . Delivery data were not available for 20 women who delivered elsewhere . Twenty women were excluded because preterm delivery was undertaken because of pregnancy abnormalities . Of the 964 women with known gestational age at delivery , 46 ( 4.8 % ) delivered at < 37 weeks and 16 ( 1.7 % ) at < 35 weeks ' gestation . Mean cervix length at 28 weeks ( 36.7 + /- 7.3 mm ) was significantly shorter than at 24 weeks ( 37.8 + /- 7.1 mm ) ( P < 0.001 ) . Cervix length at 24 and 28 weeks ' gestation was equally predictive of preterm birth . A cervix length of < or = 30 mm at 28 weeks had a sensitivity of 57.1 % , a specificity of 81.8 % , and a positive predictive value of 4.5 % for birth at < 35 weeks . Serum relaxin levels were not correlated with cervix length at either 24 or 28 weeks . Serum relaxin at 24 and 28 weeks ' gestation was not associated with preterm birth before or after controlling for patient characteristics and cervix length . CONCLUSION Serum relaxin levels at 24 and 28 weeks ' gestation are not associated with preterm birth . Although cervix length is associated with preterm birth , its positive predictive value is low . Given the lack of proven therapies for those at risk , cervix length does not appear to be a useful screening tool for preterm delivery in the general obstetric population OBJECTIVE To investigate the efficacy of vaginal progesterone to prevent early preterm birth in women with sonographic evidence of a short cervical length in the midtrimester . METHODS This was a planned , but modified , secondary analysis of our multinational , multicenter , r and omized , placebo-controlled trial , in which women were r and omized between 18 + 0 and 22 + 6 weeks of gestation to receive daily treatment with 90 mg of vaginal progesterone gel or placebo . Cervical length was measured with transvaginal ultrasound at enrollment and at 28 weeks of gestation . Treatment continued until either delivery , 37 weeks of gestation or development of preterm rupture of membranes . Maternal and neonatal outcomes were evaluated for the subset of all r and omized women with cervical length < 28 mm at enrollment . The primary outcome was preterm birth at < /= 32 weeks . RESULTS A cervical length < 28 mm was identified in 46 r and omized women : 19 of 313 who received progesterone and 27 of 307 who received the placebo . Baseline characteristics of the two groups were similar . In women with a cervical length < 28 mm , the rate of preterm birth at < /= 32 weeks was significantly lower for those receiving progesterone than it was for those receiving the placebo ( 0 % vs. 29.6 % , P = 0.014 ) . With progesterone , there were fewer admissions into the neonatal intensive care unit ( NICU ; 15.8 % vs. 51.9 % , P = 0.016 ) and shorter NICU stays ( 1.1 vs. 16.5 days , P = 0.013 ) . There was also a trend toward a decreased rate of neonatal respiratory distress syndrome ( 5.3 % vs. 29.6 % , P = 0.060 ) . CONCLUSION Vaginal progesterone may reduce the rate of early preterm birth and improve neonatal outcome in women with a short sonographic cervical length OBJECTIVES To assess the role of cervical sonography and to compare various sonographic cervical parameters in their ability to predict spontaneous preterm birth in high-risk singleton gestations . DESIGN A prospect i ve cohort of 469 high-risk gestations were longitudinally evaluated between 15 and 24 weeks ' gestation on 1265 occasions with transvaginal cervical sonography and transfundal pressure . The cervical parameters obtained were funnel width and length , cervical length , percent funneling and cervical index . The information obtained was used for patient management . Restriction of physical activities was initiated at cervical lengths of < or = 2.5 cm with cerclage as an option for cervical lengths of < or = 2.0 cm . RESULTS Receiver operating characteristic curve analyses showed that a cervical length of < or = 2.5 cm between 15 and 24 weeks ' gestation was equal to the other sonographic cervical parameters in its ability to predict spontaneous preterm birth . The sensitivities for delivery at < 28 , < 30 , < 32 and < 34 weeks ' gestation were 94 % , 91 % , 83 % and 76 % , respectively , while the negative predictive values were 99 % , 99 % , 98 % and 96 % , respectively . The placement of a cerclage did not influence the positive and negative predictive values . In comparison to women with other risk factors , cervical length was best in the prediction of preterm birth in women with a prior mid-trimester loss ; an optimal cut-off of < or = 1.5 cm had sensitivities for delivery at < 28 , < 30 , < 32 and < 34 weeks ' gestation of 100 % , 100 % 92 % and 81 % , respectively . The rate of preterm delivery at < 34 weeks ' gestation increased dramatically when the cervical length was < or = 1.5 cm . Cervical length was the only independent variable that entered the logistic regression model for the prediction of preterm delivery at < 34 weeks ' gestation . CONCLUSIONS In high-risk singleton gestations a cervical length of < or = 2.5 cm was equal to other sonographic cervical parameters in its ability to predict spontaneous preterm birth and was better for the prediction of earlier forms of prematurity ( at < 28 and < 30 weeks ) than later forms ( at < 32 and < 34 weeks ) . The optimal cervical lengths and their performance for predicting prematurity may be influenced by obstetric risk factors In a cohort of 43 women with viable , singleton pregnancies , cervical dilatation greater than 4 cm , and absent labor between 20 and 27 weeks gestation , 22 women who underwent emergency cerclage within six hours of admission , were compared prospect ively with 15 women who elected conservative bed rest treatment . The two groups were demographically similar . Emergency cervical cerclage result ed in a longer mean gestational age at delivery compared to bed rest ( p = 0.001 ) . Women treated with cerclage required a significantly shorter period of antepartum hospitalization ( p = 0.001 ) , required less tocolysis ( p = 0.005 ) , and experienced fewer preterm membrane ruptures compared to women in the bed rest group ( p = 0.01 ) , although the latency period , following preterm rupture of membranes was shorter in the cerclage group ( p = 0.005 ) . There was no statistical difference in the frequencies of chorioamnionitis , maternal morbidity and cesarean section between the two groups . Although the perinatal mortality in the two groups was not significantly different ( p = 0.3 ) , emergency cerclage result ed in a significantly higher mean birth weight compared to conservative bed rest treatment ( p Output:	Use of the ultrasonographic technique review ed in this guideline may help identify women at risk of preterm birth and , in some circumstances , lead to interventions that may reduce the rate of preterm birth .
MS212080	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Low levels of physical activity are characteristic in preschoolers . To effectively promote physical activity , it is necessary to underst and factors that influence young children 's physical activity . The present study aim ed to investigate how physical activity levels are influenced by environmental factors during recess in preschool . Methods Preschool playground observations and pedometry during recess were carried out in 39 r and omly selected preschools ( 415 boys and 368 girls ; 5.3 ± 0.4 years old ) . In order to examine the contribution of playground variables to physical activity levels , taking adjustment for clustering of subjects within preschools into account , multilevel analyses were conducted . Results During recess boys took significantly more steps per minute than girls ( 65 ± 36 versus 54 ± 28 steps/min ) . In both genders higher step counts per minute were significantly associated with less children per m2 and with shorter recess times . Only in boys a hard playground surface was a borderline significant predictor for higher physical activity levels . In girls higher step counts were associated with the presence of less supervising teachers . Playground markings , access to toys , the number of playing or aim ing equipment pieces and the presence of vegetation or height differences were not significant physical activity predictors in both genders . Conclusion In preschool children physical activity during outdoor play is associated with modifiable playground factors . Further study is recommended to evaluate if the provision of more play space , the promotion of continued activity by supervisors and the modification of playground characteristics can increase physical activity levels in preschoolers Objective : To investigate whether the distance covered in the six minute walk test was affected by walking with a group of others in comparison with performing the test alone . Methods : Eight healthy men ( mean ( SD ) age 21.0 ( 0.9 ) years ) and eight healthy women ( mean ( SD ) age 20.8 ( 2.0 ) years ) performed in r and om order two six minute walk tests either alone or in a group of four on two separate occasions one week apart . Results : Distance covered increased significantly from a mean of 653 ( 61 ) m in the individual male tests to 735 ( 79 ) m in the male group tests ( p<0.05 ) , and 616 ( 75 ) m in the individual female tests to 701 ( 54 ) m in the female group tests ( p<0.01 ) . The men increased the distance walked in six minutes by 12.5 % and the women by 13.7 % when they performed the test as a group . Conclusion : Performing the six minute walk test in a group facilitates its execution As part of the Harvard Cancer Prevention Program Project , we used a social context ual model of health behavior change to test an intervention targeting multiple risk-related behaviors in working-class , multiethnic population s. We examined the relationships between the social context ual factors in our conceptual model and changes in fruit and vegetable consumption from baseline to completion of intervention in health centers and small business studies . We analyzed change in fruit and vegetable consumption , measured at baseline and final assessment s by self-report , in 2 r and omized controlled prevention trials : 1 in small businesses ( n = 974 ) and 1 in health centers ( n = 1954 ) . Stronger social networks , social norms that were more supportive , food sufficiency , and less household crowding were associated with greater change in fruit and vegetable intake . We also observed differences between our intervention sites . Social context can play an important role in promoting changes in fruit and vegetable consumption Systematic review s that include nonr and omized studies ( NRS ) face a number of logistical challenges . However , the greatest threat to the validity of such review s arises from the differing susceptibility of r and omized controlled trials ( RCTs ) and NRS to selection bias . Groups compared in NRS are unlikely to be balanced because of the reasons leading study participants to adopt different health behaviours or to be treated differentially . Research ers can try to minimize the susceptibility of NRS to selection bias both at the design stage , for example , by matching participants on key prognostic factors , and during data analysis , for example , by regression modelling . However , because of logistical difficulties in matching , imperfect knowledge about the relationships between prognostic factors and between prognostic factors and outcome , and measurement limitations , it is inevitable that estimates of effect size derived from NRS will be confounded to some extent . Research ers , review ers and users of evidence alike need to be aware of the consequences of residual confounding . In poor quality RCTs , selection bias tends to favour the new treatment being evaluated . Selection bias need not necessarily lead to systematic bias in favour of one treatment but , even if it acts in an unpredictable way , it will still give rise to additional , nonstatistical uncertainty bias around the estimate of effect size . Systematic review s of NRS studies run the risk of compounding these biases . Nutritional choices and uptake of health education about nutrition are very likely to be associated with potential confounding factors . Therefore , pooled estimates of the effects of nutritional exposures and their confidence intervals are likely to be misleading ; review ers need to take into account both systematic and uncertainty bias OBJECTIVE The effects of positive- and negative peer modelling on children 's consumption of a novel blue food , presented in each of four snack meals during an " activity " day , were evaluated . It was predicted that : ( i ) novel food consumption would increase after positive modelling , but decrease after negative modelling ; ( ii ) modelling effects would generalise to a second novel blue food when participants were alone when they ate their snack ; ( iii ) that positive modelling would reverse the effects of negative modelling . DESIGN A mixed design was employed with r and om assignment to either Groups A , B , or C ( equal numbers of males and females per group ) . Within groups , each participant received the novel food on four snack occasions . Group A received positive modelling of blue food consumption on the first and third occasions , but were alone when they received the foods on the second and fourth occasions ; Group B had negative modelling on the first occasion , positive modelling on the third , and ate alone on the second and fourth ; Group C ate alone on all four occasions . To measure generalisation , an additional blue food was presented in all second and fourth " alone " occasions . PARTICIPANTS Thirty-five 5 - 7-year olds took part in Study 1 , and 44 3 - 4-year olds in Study 2 . RESULTS All main predictions were confirmed except that positive peer modelling did not reverse the effects of negative modelling in the 3 - 4-year olds . CONCLUSION Negative peer modelling inhibits novel food consumption , and its effects are particularly difficult to reverse in younger children Dietary patterns are useful in nutritional epidemiology , providing a comprehensive alternative to the traditional approach based on single nutrients . The Cardiovascular Risk in Young Finns Study is a prospect i ve cohort study with a 21-year follow-up . At baseline , detailed quantitative information on subjects ' food consumption was obtained using a 48 h dietary recall method ( n 1768 , aged 3 - 18 years ) . The interviews were repeated after 6 and 21 years ( n 1200 and n 1037 , respectively ) . We conducted a principal component analysis to identify major dietary patterns at each study point . A set of two similar patterns was recognised throughout the study . Pattern 1 was positively correlated with consumption of traditional Finnish foods , such as rye , potatoes , milk , butter , sausages and coffee , and negatively correlated with fruit , berries and dairy products other than milk . Pattern 1 type of diet was more common among male subjects , smokers and those living in rural areas . Pattern 2 , predominant among female subjects , non-smokers and in urban areas , was characterised by more health-conscious food choices such as vegetables , legumes and nuts , tea , rye , cheese and other dairy products , and also by consumption of alcoholic beverages . Tracking of the pattern scores was observed , particularly among subjects who were adolescents at baseline . Of those originally belonging to the uppermost quintile of pattern 1 and 2 scores , 41 and 38 % respectively , persisted in the same quintile 21 years later . Our results suggest that food behaviour and concrete food choices are established already in childhood or adolescence and may significantly track into adulthood This study investigates the effects of peer influence on the food intake of overweight and normal-weight children . A mixed factorial design was employed , with children 's weight status ( overweight vs. normal-weight ) as a between-subjects factor , and social context ( alone vs. group ) as a within-subjects factor . A total of 32 children ( n=17 overweight and n=15 normal-weight ) between the ages of 6 - 10 years participated in this study . Findings from the r and om regression model indicated that overweight children ate more when with others than when alone , while in contrast normal-weight ate more with others than they did when alone . Therefore , social context differentially impacts the eating behavior of overweight and normal-weight children . This study underscores differences in responses to the social environment between overweight and non-overweight youths , and suggests that social involvement may be an important tool in treatment and prevention programs for overweight and obesity PURPOSE The aim of the study was to investigate the tracking of physical activity ( PA ) from preschool age to adulthood in six age cohorts of males and females . METHODS A r and om sample of 3596 boys and girls age 3 - 18 yr participated in the Cardiovascular Risks in Young Finns Study in 1980 . The follow-up measurements were repeated in 1986 , 1992 , 2001 , and 2007 . The PA was measured by mother 's report in 3- and 6-yr-olds and self-report in 9-yr-olds and older . Tracking of PA was analyzed using the Spearman rank-order correlation and a simplex model . RESULTS Mother-reported PA at age 3 and 6 yr significantly predicted self-reported PA in youth and in young adulthood , and there was a significant indirect effect of mother report on adult PA 2007 in males . Simplex models that fitted the data very well produced higher stability coefficients than the Spearman rank-order correlations showing moderate or high tracking . The tracking was higher in males than that in females . CONCLUSION This study has shown that physically active lifestyle starts to develop very early in childhood and that the stability of PA is moderate or high along the life course from youth to adulthood Although Social Cognitive Theory ( B and ura , 1997 ) suggests that teacher modeling would be one of the most effective methods to encourage food acceptance by preschool children , opinions of experienced teachers have not yet been sample d , teacher modeling has rarely been examined experimentally , and it has produced inconsistent results . The present study considers opinions of teachers and conditions under which teacher modeling is effective . Study 1 was a question naire in which preschool teachers ( N=58 ) were found to rate modeling as the most effective of five teacher actions to encourage children 's food acceptance . Study 2 and Study 3 were quasi-experiments that found silent teacher modeling ineffective to encourage either familiar food acceptance ( N=34 ; 18 boys , 16 girls ) or new food acceptance ( N=23 ; 13 boys , 10 girls ) . Children 's new food acceptance was greatest in the first meal and then rapidly dropped , suggesting a " novelty response " rather than the expected neophobia . No gender differences were found in response to silent teacher modeling . Study 4 was a repeated- measures quasi-experiment that found enthusiastic teacher modeling ( " Mmm ! I love mangos ! " ) could maintain new food acceptance across five meals , again with no gender differences in response to teacher modeling ( N=26 ; 12 boys , 14 girls ) . Study 5 found that with the addition of a competing peer model , however , even enthusiastic teacher modeling was no longer effective to encourage new food acceptance and gender differences appeared , with girls more responsive to the peer model ( N=14 ; 6 boys , 8 girls ) . Thus , to encourage children 's new food acceptance , present results suggest that teachers provide enthusiastic modeling rather than silent modeling , apply such enthusiastic modeling during the first five meals before children 's " novelty response " to new foods drops , and avoid placing competing peer models at the same table with picky eaters , especially girls The purpose of this research was to compare the self-images of male and female children in order to determine whether females were at a particular disadvantage and , if so , why . A r and om sample of 1988 children from grade s 3–12 were interviewed in Baltimore in 1968 . Findings show more disturbance among White adolescent females than among White males or Black females : White girls become much more self-conscious and show greater self-image instability and somewhat lower self-esteem . Three sets of factors appear to explain part of these differences : ( 1 ) attitudes toward present and future sex role , ( 2 ) peer relationships in general and opposite sex relationships in particular , and ( 3 ) attitudes toward changing looks in adolescence The Scottish Intercollegiate Guidelines Network ( SIGN ) develops evidence based clinical guidelines for the NHS in Scotl and . The key elements of the methodology are ( a ) that guidelines are developed by multidisciplinary groups ; ( b ) they are based on a systematic review of the scientific evidence ; and ( c ) recommendations are explicitly linked to the supporting evidence and grade d according to the strength of that evidence . Until recently , the system for grading guideline recommendations was based on the work of the US Agency for Healthcare Research and Quality ( formerly the Agency for Health Care Policy and Research ) . 1 2 However , experience over more than five years of guideline development led to a growing awareness of this system 's weaknesses . Firstly , the grading system was design ed largely for application to questions of effectiveness , where r and omised controlled trials are accepted as the most robust study design with the least risk of bias in the results . However , in many areas of medical practice r and omised trials may not be practical or ethical to undertake ; and for many questions other types of study design may provide the best evidence . Secondly , guideline development groups often fail to take adequate account of the method ological quality of individual studies and the overall picture presented by a body of evidence rather than individual studies or they fail to apply sufficient judgment to the overall strength of the evidence base and its applicability to the Output:	Conclusions Although supported by weak evidence , peers appear to influence children ’s eating behaviors and physical activity . However , this influence may be moderated by the number of peers , gender , age and the perceived status of the role models .
MS212081	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: An emerging literature has begun to document the affective consequences of emotion regulation . Little is known , however , about whether emotion regulation also has cognitive consequences . A process model of emotion suggests that expressive suppression should reduce memory for emotional events but that re appraisal should not . Three studies tested this hypothesis . Study 1 experimentally manipulated expressive suppression during film viewing , showing that suppression led to poorer memory for the details of the film . Study 2 manipulated expressive suppression and re appraisal during slide viewing . Only suppression led to poorer slide memory . Study 3 examined individual differences in typical expressive suppression and re appraisal and found that suppression was associated with poorer self-reported and objective memory but that re appraisal was not . Together , these studies suggest that the cognitive costs of keeping one 's cool may vary according to how this is done BACKGROUND The amygdala is believed to play a key role in processing emotionally salient , threat-relevant , events that require further online processing by cortical regions . Emotional disorders such as depression and anxiety have been associated with hyperactivity of the amygdala , but it is unknown whether antidepressant treatment directly affects amygdala responses to emotionally significant information . METHODS The current study assessed the effects of 7 days administration of the selective serotonin reuptake inhibitor ( SSRI ) , citalopram , on amygdala responses to masked presentations of fearful and happy facial expressions in never-depressed volunteers using blood oxygenation level-dependent ( BOLD ) functional magnetic resonance imaging . A double-blind , between-groups design was used with volunteers r and omized to 20 mg/day citalopram versus placebo . RESULTS Volunteers receiving citalopram showed decreased amygdala responses to masked presentations of threat compared with those receiving placebo . Citalopram also reduced responses within the hippocampus and medial prefrontal cortex ( mPFC ) specifically during the fear-relevant stimuli . These neural differences were accompanied by decreased recognition of fearful facial expressions assessed after the scan . By contrast , there was no effect of citalopram on the neural or behavioral response to the happy facial expressions . CONCLUSIONS These results suggest a direct effect of serotonin potentiation on amygdala response to threat-relevant stimuli in humans . Such effects may be important in the therapeutic actions of antidepressants in depression and anxiety A new cognitive therapy ( CT ) program was compared with an established behavioral treatment . Sixty-two patients meeting Diagnostic and Statistical Manual of Mental Disorders ( 4th ed . ; American Psychiatric Association , 1994 ) criteria for social phobia were r and omly assigned to CT , exposure plus applied relaxation ( EXP = AR ) , or wait-list ( WAIT ) . CT and EXP = AR were superior to WAIT on all measures . On measures of social phobia , CT led to greater improvement than did EXP = AR . Percentages of patients who no longer met diagnostic criteria for social phobia at posttreatment-wait were as follows : 84 % in CT , 42 % in EXP = AR , and 0 % in WAIT . At the 1-year follow-up , differences in outcome persisted . In addition , patients in EXP = AR were more likely to have sought additional treatment . Therapist effects were small and nonsignificant . CT appears to be superior to EXP = AR in the treatment of social phobia Eyelid conditional discrimination learning ( ECDL ) is a test of discriminative aversive conditioning . It places minimal dem and s on motivation and was shown to selectively test temporal lobe function . Twenty-five unmedicated social phobia ( SP ) patients ( mean age 29.5 ± 7.0 years ) , diagnosed according to DSM-IV criteria , and 25 age- and gender-matched healthy controls ( HC , mean age 34.0 ± 8.6 years ) were examined with an ECDL paradigm . In the experiment two differently colored stimuli are r and omly presented . Only one of the stimuli ( reinforced trial ) is followed by an aversive airpuff to the cornea , as opposed to unreinforced trials not followed by an airpuff . Conditioned responses ( CRs ) consist of reflex eyelid closures already upon light presentation . HC as well as SP patients showed a significant difference between reinforced and unreinforced trials . In SP patients , CR frequency did not increase during the ECDL task , while HCs showed appropriate conditional discrimination ability . Thus the results indicate an impairment of adequate behavior modification in an aversive conditioning task in SP We have previously shown that a single dose of intravenous citalopram in healthy volunteers enhances the detection of fearful facial expressions , suggesting an effect of acute selective serotonin re-uptake inhibitor ( SSRI ) treatment on the processing of anxiety-related stimuli . The aim of the present study was to confirm and extend this finding by study ing the effects of a single dose of oral citalopram on a range of tasks design ed to assess different aspects of emotional processing . A total of 32 healthy volunteers were r and omly allocated to double-blind treatment with either citalopram 20 mg orally or placebo . Participants then completed a series of tasks assessing emotional aspects of attention ( visual-probe task ) , perception ( categorization of facial affect ) , memory ( emotional memory task ) and reactivity to threat ( emotion potentiated startle ) . Relative to placebo-treated subjects , participants treated with citalopram demonstrated improved recognition of fearful faces and increased baseline startle response . However , the citalopram group also showed an attentional bias towards positive words . Our data suggest that acute oral citalopram increases the processing of anxiety-related stimuli in healthy volunteers . This mechanism could underlie the known tendency of SSRIs to increase anxiety in patients early in treatment . Our data also suggests that some of the positive biases in emotional processing produced by SSRI treatment might be detectable at the beginning of treatment Information processing was examined in a sample of social phobic individuals using a revised version of the Stroop color-naming task . In the first of two experiments , the response latencies of social phobics and matched community controls were compared when color-naming socially threatening words , physically threatening words and color words . Social phobics demonstrated greater response latencies regardless of type of stimulus word and additional interference in color-naming social threat words compared to the control group . The second experiment examined the cognitive structural change that has been hypothesized to accompany successful treatment of individuals with an anxiety disorder . Social phobics who were treated with cognitive-behavioral group therapy , phenelzine or pill placebo were classified as treatment responders or nonresponders , and their latencies to color-naming on the Stroop task were compared . Treatment responders showed a significant reduction in latencies to color-name social threat words ( vs matched control words ) while nonresponders did not . This effect was not demonstrated with color words or physically threatening words . Clinical implication s and future research directions are discussed BACKGROUND This article presents results of the acute treatment phase of a 2-site study comparing cognitive behavioral group therapy ( CBGT ) and treatment with the monoamine oxidase inhibitor phenelzine sulfate for social phobia . METHODS One hundred thirty-three patients from 2 sites received 12 weeks of CBGT , phenelzine therapy , pill placebo administration , or educational-supportive group therapy ( an attention-placebo treatment of equal credibility to CBGT ) . The " allegiance effect , " ie , the tendency for treatments to seem most efficacious in setting s of similar theoretical orientation and less efficacious in theoretically divergent setting s , was also examined by comparing responses to the treatment conditions at both sites : 1 known for pharmacological treatment of anxiety disorders and the other for cognitive behavioral treatment . RESULTS After 12 weeks , phenelzine therapy and CBGT led to superior response rates and greater change on dimensional measures than did either control condition . However , response to phenelzine therapy was more evident after 6 weeks , and phenelzine therapy was also superior to CBGT after 12 weeks on some measures . There were few differences between sites , suggesting that these treatments can be efficacious at facilities with differing theoretical allegiances . CONCLUSIONS After 12 weeks , both phenelzine therapy and CBGT were associated with marked positive response . Although phenelzine therapy was superior to CBGT on some measures , both were more efficacious than the control conditions . More extended cognitive behavioral treatment and the combination of modalities may enhance treatment effect OBJECTIVES The present study examined whether social phobia is an anxiety disorder associated with a memory bias toward threat . DESIGN Social phobic ( N = 16 ) and non-anxious ( N = 17 ) individuals were compared on their recall of evaluative threat and neutral prose passage content . METHOD Participants were presented with two evaluative threat and two neutral prose passages and completed an immediate free recall task after each trial . RESULTS Contrary to expectation , individuals with social phobia recalled a smaller percentage of units from the evaluative threat passages than non-anxious individuals . CONCLUSION Consistent with the vigilance-avoidance theory , it is suggested that social phobia is an anxiety disorder characterized by the avoidance of elaborate processing of threatening material Specificity of neuropsychological dysfunction in obsessive-compulsive disorder ( OCD ) was assessed by comparing neuropsychological performance in 65 OCD patients , 17 social phobic patients , and 32 normal control subjects . Although both patient groups showed visual constructional impairment relative to normal subjects , only patients with social phobia showed executive dysfunction . Nonconcurrent state anxiety did not correlate with neuropsychological performance . Among anxiety disorders , neuropsychological dysfunction may not be specific to OCD , but the functions implicated may differ across patient groups Output:	The review revealed indication for decreased performance regarding visual scanning and visuoconstructional ability as well as some indication for verbal memory difficulties . It is suggested that the decreased performance should be attributed to an increased level of situational anxiety , and an engagement in disorder-related , cognitively costly activities rather than trait-like cognitive dysfunctions .
MS212082	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Aims : To examine the associations between postnatal depression in mothers and diarrhoeal illness in their infants in the first year of life in a low-income country . Methods : Using a prospect i ve cohort design , 265 infants ( n = 130 of mothers having a depressive episode according to the International Classification of Diseases , 10th revision , at 3 months postnatal and n = 135 of psychologically well mothers ) living in rural Rawalpindi , Pakistan , were followed up for 1 year . Frequency of diarrhoeal episodes was measured fortnightly by health workers using a st and ard question naire . Results : Infants of depressed mothers had significantly more diarrhoeal episodes per year than those of controls ( mean 5.5 v 4.0 ; 95 % confidence interval ( CI ) 0.9 to 2.0 ) . The relative risk of having ⩾5 diarrhoeal episodes per year in infants of depressed mothers was 2.3 ( 95 % CI 1.6 to 3.1 ) . The association remained significant after adjustment for other risk factors by multivariate analysis . Conclusions : Maternal depression is associated with infant diarrhoeal morbidity in a low-income community setting . It is independent of the effects of known factors such as undernutrition , socioeconomic status and parental education . Preventive child health programmes targeting mothers must consider their mental health Combined psychosocial and nutrition interventions improve the development of infants . However , there is a paucity of studies examining the effectiveness of such interventions in humanitarian setting s. This article examines the impact of combining a group-based psychosocial intervention with an existing emergency feeding program for internally displaced mothers in Northern Ug and a. The intervention consisted of mother and baby group sessions and home visits for mothers attending 3 emergency feeding centers . Psychosocial outcomes were compared with a contrast group of mothers who received nutritional support alone . The outcomes investigated were infant stimulation and maternal mood . After controlling for the effects of interview site and baseline scores , mothers in the intervention group ( n = 70 ) showed greater involvement with their babies , more availability of play material s , and less sadness and worry at follow-up in comparison to the contrast group ( n = 77 ) . The intervention was acceptable to the mothers and easily taught . A proportion of the mothers chose to continue the intervention spontaneously with other mothers in their neighbourhoods . Further research needs to be done to vali date these preliminary findings and explore the longer term impact on child growth and intellectual development as well as maternal mood BACKGROUND Programmes that promote early psychological development of children in the developed world have been found to be beneficial . However , such programmes are rare in underprivileged parts of the developing world . We adapted one such parent-based programme ( Learning Through Play ) for a rural Pakistani population and aim ed to study if : ( 1 ) it was acceptable to community health workers ; ( 2 ) the programme led to an improvement , after a period of 6 months , in mothers ' knowledge and attitudes about early infant development ; ( 3 ) it led to a reduction in the levels of maternal mental distress in the post-natal period . METHODS Using a cluster r and omized design with villages as unit of r and omization , 163 mothers from 24 villages in a rural sub-district of Rawalpindi , Pakistan , received the ' Learning Through Play ' programme , whereas 146 mothers from 24 villages acted as controls . Twenty-four community health workers were trained to carry out the programme . Assessment s were conducted using a specially developed 15-item Infant Development Question naire and the 20-item Self-Reporting Question naire ( SRQ ) . RESULTS Over 80 % of the community health workers trained found the programme to be relevant and were able to integrate it into their routine work . There was a significant increase in mothers ' knowledge and positive attitudes about infant development in the intervention group , compared with the control group . Women in the intervention group answered correctly 4.3 ( 95 % CI 3.7 - 14.9 , P < 0.001 ) more questions than the control group . There was no difference in levels of mental distress measured by the SRQ . CONCLUSIONS The ' Learning Through Play ' programme was successfully integrated into the existing health system and accepted by community health workers . The programme succeeded in improving the knowledge and attitudes of mothers about infant development PURPOSE This study aim ed to study the effectiveness of an emotional self-management training program to antenatal women in the prevention of postnatal depression . DESIGN AND METHODS The sample comprised 240 women who were at 32 weeks antenatal . They were r and omly assigned into the intervention group and the control group . FINDINGS On completion of the program , the intervention group reported significantly lower mean Patient Health Question naire-9 and Edinburgh Postnatal Depression Scale scores than the control group . Fewer participants from the intervention group were diagnosed as having postnatal depression using the Structured Clinical Interview for DSM-IV . PRACTICE IMPLICATION S An antenatal emotional self-management training that may lower the risk of developing postnatal depression among Chinese women is recommended BACKGROUND The risk for emotional and behavioral problems is known to be high among children of depressed mothers , but little is known about the impact of prenatal and postnatal depression on the physical health of infants . OBJECTIVE To determine whether maternal depression is a risk factor for malnutrition and illness in infants living in a low-income country . DESIGN Prospect i ve cohort study . SETTING Rural community in Rawalpindi , Pakistan . PARTICIPANTS Six hundred thirty-two physically healthy women were assessed in their third trimester of pregnancy to obtain at birth a cohort of 160 infants of depressed mothers and 160 infants of psychologically well mothers . MAIN OUTCOME MEASURES All infants were weighed and measured at birth and at 2 , 6 , and 12 months of age , and they were monitored for episodes of diarrhea and acute respiratory infections . The mothers ' mental states were reassessed at 2 , 6 , and 12 months . Data were collected on potential confounders of infant outcomes , such as birth weight and socioeconomic status . RESULTS Infants of prenatally depressed mothers showed significantly more growth retardation than controls at all time points . The relative risks for being underweight ( weight-for-age z score of less than -2 ) were 4.0 ( 95 % confidence interval [ CI ] , 2.1 to 7.7 ) at 6 months of age and 2.6 ( 95 % CI , 1.7 to 4.1 ) at 12 months of age , and the relative risks for stunting ( length-for-age z score of less than -2 ) were 4.4 ( 95 % CI , 1.7 to 11.4 ) at 6 months of age and 2.5 ( 95 % CI , 1.6 to 4.0 ) at 12 months of age . The relative risk for 5 or more diarrheal episodes per year was 2.4 ( 95 % CI , 1.7 to 3.3 ) . Chronic depression carried a greater risk for poor outcome than episodic depression . The associations remained significant after adjustment for confounders by multivariate analyses . CONCLUSIONS Maternal depression in the prenatal and postnatal periods predicts poorer growth and higher risk of diarrhea in a community sample of infants . As depression can be identified relatively easily , it could be an important marker for a high-risk infant group . Early treatment of prenatal and postnatal depression could benefit not only the mother 's mental health but also the infant 's physical health and development Objective To assess the efficacy of an intervention design ed to improve the mother-infant relationship and security of infant attachment in a South African peri-urban settlement with marked adverse socioeconomic circumstances . Design R and omised controlled trial . Setting Khayelitsha , a peri-urban settlement in South Africa . Participants 449 pregnant women . Interventions The intervention was delivered from late pregnancy and for six months postpartum . Women were visited in their homes by previously untrained lay community workers who provided support and guidance in parenting . The purpose of the intervention was to promote sensitive and responsive parenting and secure infant attachment to the mother . Women in the control group received no therapeutic input from the research team . Main outcome measures Primary outcomes : quality of mother-infant interactions at six and 12 months postpartum ; infant attachment security at 18 months . Secondary outcome : maternal depression at six and 12 months . Results The intervention was associated with significant benefit to the mother-infant relationship . At both six and 12 months , compared with control mothers , mothers in the intervention group were significantly more sensitive ( 6 months : mean difference=0.77 ( SD 0.37 ) , t=2.10 , P<0.05 , d=0.24 ; 12 months : mean difference=0.42 ( 0.18 ) , t=−2.04 , P<0.05 , d=0.26 ) and less intrusive ( 6 months : mean difference=0.68 ( 0.36 ) , t=2.28 , P<0.05 , d=0.26 ; 12 months : mean difference=−1.76 ( 0.86 ) , t=2.28 , P<0.05 , d=0.24 ) in their interactions with their infants . The intervention was also associated with a higher rate of secure infant attachments at 18 months ( 116/156 ( 74 % ) v 102/162 ( 63 % ) ; Wald=4.74 , odds ratio=1.70 , P<0.05 ) . Although the prevalence of maternal depressive disorder was not significantly reduced , the intervention had a benefit in terms of maternal depressed mood at six months ( z=2.05 , P=0.04 ) on the Edinburgh postnatal depression scale ) . Conclusions The intervention , delivered by local lay women , had a significant positive impact on the quality of the mother-infant relationship and on security of infant attachment , factors known to predict favourable child development . If these effects persist , and if they are replicated , this intervention holds considerable promise for use in the developing world . Trial registration Current Controlled Trials IS RCT N25664149 BACKGROUND The optimum way to improve the recognition and treatment of postnatal depression in developing countries is uncertain . We compared the effectiveness of a multicomponent intervention with usual care to treat postnatal depression in low-income mothers in primary -care clinics in Santiago , Chile . METHODS 230 mothers with major depression attending postnatal clinics were r and omly allocated to either a multicomponent intervention ( n=114 ) or usual care ( n=116 ) . The multicomponent intervention involved a psychoeducational group , treatment adherence support , and pharmacotherapy if needed . Usual care included all services normally available in the clinics , including antidepressant drugs , brief psychotherapeutic interventions , medical consultations , or external referral for specialty treatment . The primary outcome measure was the Edinburgh postnatal depression scale ( EPDS ) score at 3 and 6 months after r and omisation . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00518830 . FINDINGS 208 ( 90 % ) of women r and omly assigned to treatment groups completed assessment s. The crude mean EPDS score was lower for the multicomponent intervention group than for the usual care group at 3 months ( 8.5 [ 95 % CI 7.2 - 9.7 ] vs 12.8 [ 11.3 - 14.1 ] ) . Although these differences between groups decreased by 6 months , EPDS score remained better in multicomponent intervention group than in usual care group ( 10.9 [ 9.6 - 12.2 ] vs 12.5 [ 11.1 - 13.8 ] ) . The adjusted difference in mean EPDS between the two groups at 3 months was -4.5 ( 95 % CI -6.3 to -2.7 ; p<0.0001 ) . The decrease in the number of women taking antidepressants after 3 months was greater in the intervention group than in the usual care group ( multicomponent intervention from 60/101 [ 59 % ; 95 % CI 49 - 69 % ] to 38/106 [ 36 % ; 27 - 46 % ] ; usual care from 18/108 [ 17 % ; 10 - 25 % ] to 11/102 [ 11 % ; 6 - 19 % ] ) . INTERPRETATION Our findings suggest that low-income mothers with depression and who have newly born children could be effectively helped , even in low-income setting s , through multicomponent interventions . Further refinements to this intervention are needed to ensure treatment compliance after the acute phase BACKGROUND Community mobilisation through participatory women 's groups might improve birth outcomes in poor rural communities . We therefore assessed this approach in a largely tribal and rural population in three districts in eastern India . METHODS From 36 clusters in Jharkh and and Orissa , with an estimated population of 228 186 , we assigned 18 clusters to intervention or control using stratified r and omisation . Women were eligible to participate if they were aged 15 - 49 years , residing in the project area , and had given birth during the study . In intervention clusters , a facilitator convened 13 groups every month to support participatory action and learning for women , and facilitated the development and implementation of strategies to address maternal and newborn health problems . The primary outcomes were reductions in neonatal mortality rate ( NMR ) and maternal depression scores . Analysis was by intention to treat . This trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT Output:	Where assessed , benefits to the child included improved mother-infant interaction , better cognitive development and growth , reduced diarrhoeal episodes and increased immunization rates . CONCLUSION In LAMI countries , the burden of CPMDs can be reduced through mental health interventions delivered by supervised non-specialists .
MS212083	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To determine the prevalence , correlates and recognition of depression among in patients of general hospitals in Wuhan , China . METHOD A total of 513 patients were r and omly selected from 1923 in patients from three general hospitals and evaluated with a Chinese version of the Structured Clinical Interview for Diagnostic and Statistical Manual-IV Axis I disorders by eight psychiatrists . Logistic regression was used to identify factors that were associated with depression . RESULTS The prevalence ( 95 % confidence interval ) of all current depressive disorders and major depressive disorder ( MDD ) was found to be 16.2 % ( 13.0 - 19.4 % ) and 9.4 % ( 6.8 - 11.9 % ) , respectively . The correlates for depression include higher hospital class , divorce/being widowed/separation , low family income , chronic diseases , lack of medical insurance , dwelling in rural area , suffering from severe illness and multiple hospitalization history . None of the patients with current MDD were detected , treated or referred to psychiatric consultation . CONCLUSIONS The prevalence of depression among in patients of general hospitals in Wuhan , China , was high . None of the depressive patients were recognized or treated for depression , indicating a serious neglect of depression in general hospitals . Our studies suggest an urgent need to improve clinicians ' ability to detect and treat depression BACKGROUND Rehospitalization occurs in approximately 20 % of medical in patients within 90 days of discharge . Rehospitalization accounts for considerable morbidity , mortality , and costs . Identification of risk factors could lead to interventions to reduce rehospitalization . The objective of the study was to determine if physical and mental health , substance abuse , and social support are risk factors for rehospitalization . METHOD This was a prospect i ve cohort study in an innercity population conducted from September 2002 to September 2004 . Participants included 144 adult in patients with at least 1 hospital admission in the past 6 months . Measurements included age , length of stay , number of admissions in the past year , and medical comorbidity as well as measures of depression , alcohol and drug abuse , social support , and health-related quality of life . The outcome studied was the rehospitalization status of participants within 90 days of the index hospitalization . RESULTS The mean age of the subjects was 54.8 years ; 48 % were black and 78 % spoke English as a primary language . Subjects were admitted a mean of 2.5 times in the year before the index admission . Sixty-four patients ( 44 % ) were subsequently rehospitalized within 90 days after the index admission . In bivariate analysis , rehospitalized patients had more prior admissions ( median of 3.0 vs. 2.0 admissions , p = .002 ) , greater medical comorbidity ( mean Charlson Comorbidity Index score of 2.6 vs. 2.0 , p = .04 ) , and poorer physical functional status ( mean SF-12 physical component score of 31.5 vs. 36.2 , p = .03 ) . A logistic regression model , including prior admissions in the last year , comorbidity , physical functional status , and depression , showed that depression tripled the odds of rehospitalization ( odds ratio = 3.3 , 95 % CI = 1.2 to 9.3 ) . This model had fair accuracy in identifying patients at greatest risk for rehospitalization ( c statistic = 0.72 ) . CONCLUSIONS Hospitalized patients with a history of prior hospitalization within 6 months who screen positive for depression are 3 times more likely to be rehospitalized within 90 days in this relatively high-risk population . Screening during hospitalization for depressive symptoms may identify those at risk for rehospitalization OBJECTIVES To identify variables associated with mortality in patients admitted to the hospital for acute exacerbation of COPD . DESIGN Prospect i ve cohort study . SETTING Acute-care hospital in Barcelona ( Spain ) . PATIENTS One hundred thirty-five consecutive patients hospitalized for acute exacerbation of COPD , between October 1996 and May 1997 . MEASUREMENTS AND RESULTS Clinical , spirometric , and gasometric variables were evaluated at the time of inclusion in the study . Socioeconomic characteristics , comorbidity , dyspnea , functional status , depression , and quality of life were analyzed . Mortality at 180 days , 1 year , and 2 years was 13.4 % , 22 % , and 35.6 % , respectively . Sixty-four patients ( 47.4 % ) were dead at the end of the study ( median follow-up duration , 838 days ) . Greater mortality was observed in the bivariate analysis among the oldest patients ( p < 0.0001 ) , women ( p < 0.01 ) , and unmarried patients ( p < 0.002 ) . Hospital admission during the previous year ( p < 0.001 ) , functional dependence ( Katz index ) [ p < 0.0004 ] , greater comorbidity ( Charlson index ) [ p < 0.0006 ] , depression ( Yesavage Scale ) [ p < 0.00001 ] ) , quality of life ( St. George 's Respiratory Question naire [ SGRQ ] ) [ p < 0.01 ] , and PCO(2 ) at discharge ( p < 0.03 ) were also among the significant predictors of mortality . In the multivariate analysis , the activity SGRQ subscale ( p < 0.001 ; odds ratio [ OR ] , 2.62 ; confidence interval [ CI ] , 1.43 to 4.78 ) , comorbidity ( p < 0.005 ; OR , 2.2 ; CI , 1.26 to 3.84 ) , depression ( p < 0.004 ; OR , 3.6 ; CI , 1.5 to 8.65 ) , hospital readmission ( p < 0.03 ; OR , 1.85 ; CI , 1.26 to 3.84 ) , and marital status ( p < 0.0002 ; OR , 3.12 ; CI , 1.73 to 5.63 ) were independent predictors of mortality . CONCLUSIONS Quality of life , marital status , depressive symptoms , comorbidity , and prior hospital admission provide relevant information of prognosis in this group of COPD patients Background The results of R and omized Controlled Trials ( RCTs ) on time-to-event outcomes that are usually reported are median time to events and Cox Hazard Ratio . These do not constitute the sufficient statistics required for meta- analysis or cost-effectiveness analysis , and their use in secondary analyses requires strong assumptions that may not have been adequately tested . In order to enhance the quality of secondary data analyses , we propose a method which derives from the published Kaplan Meier survival curves a close approximation to the original individual patient time-to-event data from which they were generated . Methods We develop an algorithm that maps from digitised curves back to KM data by finding numerical solutions to the inverted KM equations , using where available information on number of events and numbers at risk . The reproducibility and accuracy of survival probabilities , median survival times and hazard ratios based on reconstructed KM data was assessed by comparing published statistics ( survival probabilities , medians and hazard ratios ) with statistics based on repeated reconstructions by multiple observers . Results The validation exercise established there was no material systematic error and that there was a high degree of reproducibility for all statistics . Accuracy was excellent for survival probabilities and medians , for hazard ratios reasonable accuracy can only be obtained if at least numbers at risk or total number of events are reported . Conclusion The algorithm is a reliable tool for meta- analysis and cost-effectiveness analyses of RCTs reporting time-to-event data . It is recommended that all RCTs should report information on numbers at risk and total number of events alongside KM curves Hospitalization is associated with a long-term increased risk for death , especially in older persons ( 1 - 4 ) . Although the mediators for this increased risk have not been fully eluci date d , depression may play an important role . Because depression is common in hospitalized older patients , an association between depression and mortality in this population would be of significant clinical importance ( 5 - 13 ) . The hypothesis that depression may be a mediator of death in hospitalized patients is supported by studies demonstrating that depressive symptoms are associated with increased mortality in community-dwelling patients and in highly selected groups of hospitalized older patients , such as those with acute myocardial infa rct ion ( 14 - 18 ) . These studies have often been limited by inadequate accounting for the complex interrelations between depressive symptoms and other predictors of death , such as acute physiologic impairment , chronic comorbid illness , functional impairment , and cognitive impairment . Because depressive symptoms are clearly correlated with and may partly be the result of these other factors ( 5 , 19 - 20 ) , improving our underst and ing of the relation between depression and death requires use of st and ardized methods to measure and adjust for confounders . We tested the hypothesis that depressive symptoms are associated with long-term mortality in hospitalized older patients . We demonstrated previously that depressive symptoms are strongly associated with adverse health status outcomes in hospitalized medical patients through 90 days after admission ( 21 ) . However , our initial study found no association between depressive symptoms and mortality during the first 90 days after admission ( 21 ) . In this report , we extend mortality follow-up to 3 years by merging our data with a national mortality data base . Furthermore , we adjusted for st and ard measures of physiologic impairment , comorbid illness , and functional impairment at hospital admission to control for the possibility that higher levels of these confounders in patients with more depressive symptoms affect the association between depressive symptoms and death . Methods Patients Patients were drawn from serial , prospect i ve longitudinal studies of functional change in older hospitalized patients on the general medical service of University Hospitals of Clevel and . The inclusion and exclusion criteria for these studies are described elsewhere ( 3 , 21 , 22 ) . The first study enrolled 206 patients 75 years of age or older who were admitted between March 1990 and July 1990 . The second study , a controlled trial of an intervention to improve functional outcomes , enrolled 651 patients 70 years of age or older who were admitted between November 1990 and March 1992 . The first study , which was a pilot study for the second study , enrolled consecutive patients . The second study r and omly assigned patients to an intervention design ed to improve functional outcomes in older persons or to usual care ( 22 ) . In each study , patients admitted to the intensive care unit , telemetry service , or oncology service were excluded . Data collection procedures in both studies were almost identical . Other than a slightly higher mean patient age in the first study cohort , the demographic , clinical , and functional characteristics of patients in the first study , the control group of the second study , and the intervention group of the second study were similar . Additional analyses that adjusted for whether patients were in the first study cohort or the control group compared with the intervention group of the second study cohort yielded results that were almost identical to the results reported here . Of 857 older patients enrolled in the two studies , 284 were excluded from the current study because they were too ill or confused to be interviewed about depressive symptoms at the time of admission ( n=164 ) , were admitted from nursing homes ( n=38 ) , were not available for interview ( n=37 ) , declined interview ( n=27 ) , or died before being approached ( n=18 ) . We excluded patients admitted from nursing homes because interview data were less consistently obtained from these patients . Thus , the analytic sample for this study comprised 573 patients . Assessment of Depressive Symptoms Within 48 hours of admission , patients were interviewed by using the 15-item Geriatric Depression Scale to assess depressive symptoms over the past week ( 23 , 24 ) . The Geriatric Depression Scale is well suited for use in acutely ill older persons because it focuses on symptoms of depression that are less likely to be directly influenced by somatic illness . Examples of items on this scale include feeling bored , dropping activities and interests , feeling helpless , feeling worthless , feeling that life is empty , feeling that others are better off , preferring to stay at home instead of doing new things , and feeling hopeless . We divided patients into those reporting five or fewer symptoms and those reporting six or more symptoms ; these are commonly recommended cutoffs on the 15-item Geriatric Depression Scale ( 24 - 26 ) . Measurement of Mortality We determined mortality and date of death during the 3 years after hospitalization by merging our files with the National Death Index , a data base of all deaths in the United States generated from state death certificates . Its sensitivity and specificity have been reported to be 98 % and 100 % , respectively ( 27 ) . Measurement of Potential Confounders Shortly after admission , we surveyed each patient 's primary nurse about the patient 's independence in six activities of daily living ( dressing , bathing , grooming , toileting , transferring , and eating ) based on the scale of Katz ( 28 ) . Within 48 hours of admission , we administered to patients the first 21 items of the 30-item Folstein Mini-Mental State Examination ( 29 ) . To minimize respondent burden , we used only the first 21 items . Scores on the 21-item instrument have previously been shown to correlate highly ( r=0.9 ) with scores on the 30-item instrument and to have construct validity on the basis of their strong association with functional outcomes ( 30 ) . Data gathered from medical records included the reason for admission , the components of the Acute Physiology and Chronic Health Evaluation ( APACHE ) II score ( 31 ) , and the components of the weight Output:	Depressive symptoms were common in medical in patients and are associated with an increased risk of adverse events postdischarge .
MS212084	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Summary BACKGROUND : The aim of this study was to compare the efficacy and side effects of gabapentin , amitriptyline , and their combination in women with chronic pelvic pain . METHODS : In this open-label , prospect i ve , r and omized trial , 56 women with chronic pelvic pain were investigated with a two-year follow-up at the Vienna Medical University Hospital . If pain intensity assessed by a visual analog scale ( VAS ) was 5 or more ( 0 , no pain ; 10 , maximal pain ) , despite analgesic therapy using the nonopioid drug metamizol together with weak opioids , patients were r and omized to receive gabapentin ( n = 20 ) , amitriptyline ( n = 20 ) , or a combination of both drugs ( n = 16 ) . Doses of gabapentin and amitriptyline were increased to maximum daily doses of 3600 mg and 150 mg , respectively , until sufficient pain relief or the occurrence of side effects . VAS and side effects were evaluated before treatment and at 1 , 3 , 6 , 12 and 24 months afterwards . RESULTS : All patients experienced significant pain relief during the observation period . However , after 6 , 12 and 24 months , pain relief was significantly better in patients receiving gabapentin either alone or in combination with amitriptyline than in patients receiving monotherapy with amitriptyline ( gabapentin : 0 months , 7.7 ± 1.5 ; 6 months , 1.6 ± 0.9 ; 12 months , 1.5 ± 0.9 ; 24 months , 1.9 ± 0.9 ; amitriptyline : 0 months , 7.3 ± 1.5 ; 6 months , 2.2 ± 1.6 ; 12 months , 2.2 ± 1.6 ; 24 months ; 3.4 ± 0.9 ; amitriptyline-gabapentin : 0 months , 7.6 ± 0.8 ; 6 months , 1.3 ± 0.9 ; 12 months , 1.7 ± 1.0 ; 24 months , 2.3 ± 0.9 ) . Side effects were lower in the gabapentin group than in the two other groups , the difference reaching statistical significance after three months ( P < 0.05 ) . CONCLUSION : Gabapentin alone or in combination with amitriptyline is better than amitriptyline alone in the treatment of female chronic pelvic pain . ZusammenfassungEINLEITUNG : Gegenst and der Studie war der Vergleich der Wirksamkeit und Verträglichkeit von Gabapentin bzw . Amitriptylin allein mit der Kombination der beiden Medikamente bei chronischen Unterbauchschmerzen ( chronic pelvic pain , CPP ) . METHOD EN : 56 weibliche Patientinnen mit chronischen Unterbauschmerzen wurden bei der prospektiven , r and omisierten Open-label-Studie mit einem 2-jährigem Follow-up an der Schmerzambulanz der Universitätsklinik Wien , Österreich , eingeschlossen . Wenn die Schmerzintensität trotz analgetischer Therapie mit dem Nichtopioid Metamizol und einem schwachen Opioid gemessen auf der visuellen Analogskala ( VAS ) bei 5 oder darüber lag ( 0 , kein Schmerz ; 10 , schlimmster vorstellbarer Schmerz ) , wurden die Patientinnen r and omisiert einem der drei Beh and lungsarme zugeteilt ( Gabapentin , n = 20 ; Amitriptylin , n = 20 , oder beides , n = 16 ) . Die Medikamentengaben von Gabapentin bzw . Amitriptylin wurden auf eine tägliche Dosis von 3600 mg bzw . 150 mg gesteigert , bis eine suffiziente Schmerzerleichterung erreicht war oder unerwünschte Nebenwirkungen auftraten . VAS-Werte wurde vor Beginn der Beh and lung und 1 , 3 , 6 , 12 und 24 Monate danach erhoben . ERGEBNISSE : Alle Patientinnen erfuhren während des Beobachtungszeitraumes eine signifikante Schmerzreduktion . Dennoch war die Schmerzreduktion bei Patientinnen , die Gabapentin allein oder in Kombination mit Amitriptylin erhalten hatten , signifikant höher als unter Monotherapie mit Amitriptylin ( Gabapentin : 0 , 7,7 ± 1,5 ; 6 , 1,6 ± 0,9 ; 12 , 1,5 ± 0,9 ; 24 , 1,9 ± 0,9 ; Amitriptylin : 0 , 7,3 ± 1,5 ; 6 , 2,2 ± 1,6 ; 12 , 2,2 ± 1,6 ; 24 , 3,4 ± 0,9 ; Amitriptylin-Gabapentin : 0 , 7,6 ± 0,8 ; 6 , 1,3 ± 0,9 ; 12 , 1,7 ± 1,0 ; 24 , 2,3 ± 0,9 ) . Unerwünschte Nebenwirkungen traten signifikant seltener in der Gabapentin-Gruppe auf als in den beiden and eren Gruppen ( P < 0,05 ) . KONKLUSION : Diese Ergebnisse legen nahe , dass die Pharmakotherapie mit dem Antikonvulsivum Gabapentin die Beh and lung von chronischen Unterbauchschmerzen bei ambulanten Patientinnen verbessert OBJECTIVE To examine the prevalence of migraine in women with chronic pelvic pain with and without endometriosis . DESIGN Prospect i ve study of headache , pelvic pain , and quality of life before laparoscopic surgery for pelvic pain . Endometriosis was diagnosed pathologically . Headaches were classified as migraine or non-migraine using International Headache Society criteria . SETTING Clinical research hospital . PATIENT(S ) 108 women in a clinical trial for chronic pelvic pain ( NCT00001848 ) . INTERVENTION(S ) Laparoscopy to diagnose endometriosis , assessment by neurologist to assess headaches . MAIN OUTCOME MEASURE(S ) Prevalence of migraine and other headaches in women with chronic pelvic pain with or without endometriosis . Headache frequency , severity and relationship to pelvic pain and endometriosis . RESULT ( S ) Lifetime prevalence of definite or possible migraine was 67 % of women with chronic pelvic pain . An additional 8 % met criteria for possible migraine . Migraine was no more likely in women with endometriosis than those without . Women with the most severe headaches had a lower quality of life compared with those with pelvic pain alone . CONCLUSION ( S ) Migraine headache is common in women with chronic pelvic pain , regardless of endometriosis , and contributes to disability in those with both conditions . The strong association suggests a common pathophysiology Chronic pelvic pain ( CPP ) in women is often debilitating and isolating . Problems with diagnosis continue to make CPP one of the most perplexing conditions in gynaecology , and one of the most difficult to treat BACKGROUND Chronic pelvic pain has often been described as a major women 's health issue , but no information exists on the extent of the problem in the United Kingdom . AIM To investigate the community prevalence of chronic pelvic pain and its effect on the lives of consulting and non-consulting women . DESIGN OF STUDY Postal question naire survey . SETTING Women aged 18 to 49 ( n = 3916 ) r and omly selected from the Oxfordshire Health Authority Register . METHOD The question naire response rate ( adjusted for non-deliveries ) was 74 % ( 2304/3106 ) . Chronic pelvic pain was defined as recurrent or constant pelvic pain of at least six months ' duration , unrelated to periods , intercourse , or pregnancy . Case subgroups comprised recent consulters , past consulters , and non-consulters . Women who reported dysmenorrhoea alone formed a comparison group . RESULTS The three-month prevalence of chronic pelvic pain was 24.0 % ( 95 % CI = 22.1 % to 25.8 % ) . One-third of women reported pain that started more than five years ago . Recent consulters ( 32 % of cases ) were most affected by their symptoms in terms of pain severity , use of health care , physical and mental health scores , sleep quality , and pain-related absence from work . Non-consulters ( 41 % of cases ) did not differ from women with dysmenorrhoea in terms of symptom-related impairment . Irrespective of consulting behaviour , a high rate of symptom-related anxiety was found in women with chronic pelvic pain ( 31 % ) compared with women with dysmenorrhoea ( 7 % ) . CONCLUSIONS This study showed a high community prevalence of chronic pelvic pain in women of reproductive age . Cases varied substantially in the degree to which they were affected by their symptoms . The high symptom-related anxiety in these women emphasises the need for more information about chronic pelvic pain and its possible causes Vulvar vestibulitis syndrome ( VVS ) is a common cause of dyspareunia in pre‐menopausal women . Recent evidence points to the importance of the sensory component in VVS , particularly the heightened processing of tactile and pain sensation in the vulvar vestibule . The goal of the present study was to examine the neural basis of heightened sensitivity to touch ( i.e. allodynia ) in women with VVS . Using functional magnetic resonance imaging , we compared regions of neural activity in 14 women with VVS and 14 age‐ and contraceptive‐matched control women in response to the application of mild and moderate pressure to the posterior portion of the vulvar vestibule . Intensity and unpleasantness ratings were recorded after each scan ; these ratings were significantly higher for women with VVS than controls . All women with VVS described moderate pressure as painful and unpleasant , and 6 of the 14 women with VVS described mild pressure as painful and unpleasant . In contrast , none of the stimuli was painful for control women . Correspondingly , women with VVS showed more significant activations during pressure levels that they found to be either painful or non‐painful than did controls during comparable pressure levels . During pressure described as painful by women with VVS , they had significantly higher activation levels in the insular and frontal cortical regions than did control women . These results suggest that women with VVS exhibit an augmentation of genital sensory processing , which is similar to that observed for a variety of syndromes causing hypersensitivity , including fibromyalgia , idiopathic back pain , irritable bowel syndrome , and neuropathic pain Abstract Pain symptoms of many disorders are reported to vary with menstrual stage . This study investigated how pain thresholds to electrical stimulation of the skin , subcutis and muscle tissue varied with menstrual stage in normal women and compared these variations with those in women with dysmenorrhea and in healthy men at matched intervals . Thresholds of the three tissues were measured four times during the course of one menstrual cycle at four sites . Two of the sites were on the abdomen within the uterine viscerotome ( abdomen‐rectus abdominis , left and right ) and two were outside it on the limbs ( leg‐quadriceps , arm‐deltoid ) . Calculated from the beginning of menstruation ( day 0 ) , the menstrual phases studied were menstrual ( days 2–6 ) , periovulatory ( days 12–16 ) , luteal ( days 17–22 ) and premenstrual ( days 25–28 ) . Spontaneous pain associated with menstruation was measured from diary estimates on a VAS scale . Menstrual phase , dysmenorrhea and tissue : Whereas the highest thresholds always occurred in the luteal phase regardless of segmental site or stimulus depth , the lowest thresholds occurred in the periovulatory stage for skin , whereas those for muscle/subcutis occurred perimenstrually . Dysmenorrhea accentuated the impact of menstrual phase . For non‐dysmenorrheic women menstrual trends were significant only in abdominal muscle and subcutis , but for dysmenorrheic women the trends were also significant in abdominal skin and in limb muscle and subcutis . Dysmenorrhea also lowered thresholds mainly in muscle and sometimes in subcutis , but never in skin , with the greatest hyperalgesic effects in left abdominis muscle . Segmental site : Abdominal sites were more vulnerable to menstrual influences than limb sites . Muscle thresholds , but not skin or subcutis thresholds , were significantly lower in abdomen than in limbs , particularly in dysmenorrheic women . The amount of abdominal muscle hyperalgesia correlated significantly with the amount of spontaneous menstrual pain . Sex differences : Only minor sex differences were observed for pain thresholds of the arm and leg , but there was a unanimous refusal by men , but not by women , to be tested at abdominal sites . These results indicate that menstrual phase , dysmenorrhea status , segmental site , tissue depth and sex all have unique interacting effects on pain thresholds , thus adding more items to the lengthy and still‐growing list of biological factors that enter into an individual 's judgment of whether or not a stimulus is painful Introduction Chronic pelvic pain ( CPP ) affects > 1 million UK women . Annual healthcare costs are estimated at > £ 150 million . Proven interventions for CPP are limited , and treatment is often unsatisfactory . Gabapentin is increasingly prescribed due to reports of effectiveness in other chronic pain conditions , but there are insufficient data supporting value in CPP specifically . The mechanism by which gabapentin exerts its analgesic action is unknown . Given the prevalence and costs of CPP , the authors believe that a large , Output:	RESULTS CPP is associated with central changes similar to those identified in other pain conditions . Specifically these include , alterations in the behavioural and central response to noxious stimulation , changes in brain structure ( both increases and decreases in the volume of specific brain regions ) , altered activity of both the hypothalamic-pituitary-adrenal axis and the autonomic nervous system ( ANS ) and psychological distress . CONCLUSIONS The evidence review ed in this paper demonstrates that CPP is associated with significant central changes when compared with healthy pain-free women . Moreover , the presence of these changes has the potential to both exacerbate symptoms and to predispose these women to the development of additional chronic conditions .
MS212085	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Steroid-infused absorbable nasal dressings after endoscopic sinus surgery ( ESS ) have been used to improve wound healing and to reduce the recurrence of polyps . However , their systemic effects are not well known . The purpose of this study was to evaluate the systemic effects and safety of steroid-impregnated absorbable nasal packing after ESS . Methods Patients who underwent bilateral ESS for chronic rhinosinusitis were recruited and r and omized into two groups . Ten patients in the triamcinolone ( TA ) group received a TA ( 20 mg)-soaked bioabsorbable dressing in both nasal cavities while 10 patients in the control group took saline-impregnated dressing in both nasal cavities . Nasal dressings were not removed until postoperative day 10 . Serum cortisol , 12-hour urine cortisol , serum adrenal-corticotropic hormone ( ACTH ) , and serum osteocalcin were measured preoperatively and on postoperative days 2 and 10 . Serum cortisol levels were checked 1 day after surgery additionally , while urine cortisol levels were not checked at postoperative day 10 . Results All 20 patients completed this study . The serum cortisol levels were significantly suppressed at postoperative days 1 and 2 in the TA group . Serum ACTH and 12-hour urine cortisol levels were lower 2 days after surgery in the TA group , although these changes were not statistically significant . There were no differences in all other parameters between the TA and control groups on postoperative day 10 . Conclusions TA-impregnated nasal dressings suppress serum cortisol levels during the early postoperative period . This systemic effect was recovered gradually and normalized 10 days after the operation Objective . Endoscopic sinus surgery ( ESS ) for chronic rhinosinusitis ( CRS ) may be compromised by postoperative inflammation , polyposis , and adhesions , often requiring subsequent intervention . To address this issue , the authors investigated the safety and effectiveness of controlled delivery of mometasone furoate to the sinus mucosa via bioabsorbable implants deployed at the time of ESS . Study Design . Prospect i ve , multicenter , r and omized , controlled , double-blind trial using an intrapatient control design . Setting . Otolaryngology – head and neck surgery centers ; both academic and private practice s. Subjects and Methods . The study enrolled 105 patients with CRS undergoing bilateral ethmoidectomy to compare the effect of drug-releasing to non-drug-releasing implants using an intrapatient control design . Postoperative interventions , polyposis , and adhesions were assessed postoperatively . Efficacy was determined through independent analysis of r and omized video-endoscopies by 3 blinded sinus surgeons . Safety assessment s included ocular examinations . Results . Implants were successfully deployed in all 210 ethmoid sinuses . Compared with control sinuses with non-drug-releasing implants , the drug-releasing implant provided a 29.0 % relative reduction in postoperative interventions ( P = .028 ) and a 52 % ( P = .005 ) decrease in lysis of adhesions . The relative reduction in frank polyposis was 44.9 % ( P = .002 ) . Similar reductions were observed in real-time grading performed by the clinical investigators . No clinical ly significant changes from baseline in intraocular pressure or cataracts were observed . Conclusion . This study provides a high level of evidence that use of steroid-releasing implants that apply a sustained release of corticosteroid improves surgical outcomes by reducing synechiae formation , polyposis , and the need for postoperative interventions , with no observable ocular safety risk Background Nasal packing is usually performed to control bleeding after endoscopic sinus surgery ( ESS ) . Although new packing material s have been developed , they still cause pain . This study was design ed to evaluate the effect of lidocaine-soaked packs on pain after ESS . Methods A prospect i ve , r and omized , double-blind controlled trial was conducted in 63 patients with CRS undergoing ESS . At the conclusion of the operation , 2 % lidocaine-soaked biodegradable synthetic polyurethane foam and saline-soaked polyurethane foam were inserted in both nasal cavities of 31 patients and 32 control patients , respectively . The same lidocaine or saline was reapplied into the nasal packs at postoperative 8 hours . Pain was evaluated using a visual analog scale at postoperative 1 , 4 , 8 , 16 , 20 , and 24 hour(s ) . The number of gauze that cleaned the blood around the nose was counted . Heart rate , rhythm , and blood pressures were checked preoperatively and postoperatively to evaluate the influence of lidocaine on vital signs . Results Postoperative pain decreased in lidocaine group at all of the postoperative time periods ( p < 0.05 ) . Lidocaine reduced postoperative bleeding at postoperative 8 and 24 hours . Changes of blood pressure from preoperative values in the lidocaine group were not different from those in the control group ( p > 0.05 ) . Heart rate in the lidocaine group was more stable than that in the control group ( p < 0.05 ) . Conclusion Lidocaine-soaked packs significantly reduced postoperative pain without serious changes on vital sign . These findings suggest that topical lidocaine application to nasal packs could be a useful method to reduce pain during the early postoperative period after ESS OBJECTIVES We sought to determine the efficacy of MeroGel , an absorbable hyaluronic acid nasal dressing ( HA ) in reducing synechia after functional endoscopic sinus surgery ( FESS ) compared with Merocel , a nonabsorbable packing ( NAP ) requiring removal . METHODS We conducted a blinded , r and omized , controlled trial of 37 patients requiring bilateral FESS for chronic sinusitis . Patients were r and omized to placement of HA within the right or left middle meatus and NAP on the other side . Patients were evaluated at 2 , 4 , 6 , and 8 weeks postoperatively . RESULTS Blinded evaluation revealed 5 patients ( 14 % ) with synechia at last follow-up : 3 sides ( 8 % ) with HA and 3 ( 8 % ) with NAP . Thirteen patients ( 35 % ) had synechia at any visit , 10 sides ( 27 % ) with HA and 9 ( 24 % ) with NAP . Seven patients ( 19 % ) required lysis of synechia , 5 sides ( 14 % ) with HA and 3 ( 8 % ) with NAP . CONCLUSION We found no statistically significant difference between HA and NAP dressings Background The aim of this study was to determine whether there was any benefit or detrimental consequences of placing a hyaluronic acid pack ( Merogel ) into the middle meatus after endoscopic sinus surgery ( ESS ) . Methods A r and omized controlled blinded study was performed in 42 patients with chronic sinusitis undergoing ESS . The patients were r and omized to receive Merogel on one side and no packing on the other side . Patients were assessed at 2 , 4 , and 6–8 weeks after surgery and the presence of synechia , edema , and infection was noted with the observer blinded to the side that had received the Merogel . Results At 2 weeks the side packed with Merogel had 35 % synechiae , 83 % edema , and 30 % mucopurulent discharge and on the control side the figures were similar with 22.5 % synechiae , 83 % edema , and 28 % mucopurulent discharge . In both groups these figures improved over the observation period but percentages in the groups remained similar . At no time point was the difference between the packed and unpacked sides statistically significant for any of the measures when assessed with Fisher 's exact test . Conclusion Merogel nasal packing has no significant beneficial or detrimental effect in terms of synechia , edema , or infection when placed in the middle meatus after ESS OBJECTIVES /HYPOTHESIS Disease recurrence and adverse wound healing in the form of inflammation , polyposis , adhesions , and middle turbinate lateralization may induce suboptimal outcomes following sinus surgery . The study objective was to assess the safety and effectiveness of a bioabsorbable , steroid-eluting implant used following functional endoscopic sinus surgery in patients with chronic rhinosinusitis ( CRS ) . STUDY DESIGN Prospect i ve , multicenter , single-cohort trial enrolling 50 patients . METHODS The study allowed bilateral or unilateral steroid-eluting implant placement . Oral and topical steroids were withheld for 60 days postoperatively . Endoscopic follow-up was performed to 60 days . Patient-reported outcomes ( Sino-Nasal Outcome Test-22 Question naire , Rhinosinusitis Disability Index ) were collected to 6 months . Efficacy was assessed by grading inflammation , polyp formation , adhesions , and middle turbinate position . Safety assessment included ocular exams at baseline and 30 days . RESULTS Implants were successfully placed in all 90 sinuses . Mean inflammation scores were minimal at all time points . At 1 month , the prevalence of polypoid edema was 10.0 % , significant adhesions 1.1 % , and middle turbinate lateralization 4.4 % . Changes from baseline in patient-reported outcomes were statistically significant ( P < .0001 ) . No clinical ly significant changes from baseline in intraocular pressure occurred . CONCLUSIONS This consecutive case series provides clinical evidence of the safety , effectiveness , and clinical utility of a bioabsorbable steroid-eluting implant for use in CRS patients . The implant was associated with favorable rates of sinus patency . At 1 month , minimal degrees of inflammation and adhesions were observed , suggesting a positive clinical impact of local steroid delivery without evidence of ocular risk Nasal packings can aid in control of postoperative bleeding and healing following functional endoscopic sinus surgery ( FESS ) , but traditional non-resorbable stents have several inherent drawbacks . We performed a r and omized , controlled , multicenter clinical trial to assess efficacy of resorbable nasal packing in patients undergoing FESS for chronic rhinosinusitis . A total of 66 patients for 88 nasal cavities were r and omized to receive either hyaluronan resorbable packing ( MeroGel ® ) or st and ard non-resorbable nasal dressing after FESS . All underwent preoperative rhinoscopy , CT of sinuses , and , after surgery , were reassessed by rhinoscopy at 2 , 4 , and 12 weeks in blinded fashion . A total of 44 nasal cavities ( MeroGel ® -group ) received resorbable packing , whereas the remaining 44 were packed with non-resorbable nasal dressing . At follow-up endoscopic visit , the presence of nasal synechia was evaluated as primary outcome . Moreover , the tolerability and surgical h and ling properties of MeroGel ® and its comfort were assessed by surgeons and patients . Preoperative severity of rhinosinusitis was similar in both groups . No significant adverse events were observed in all patients . Follow-up endoscopy showed a lower proportion of nasal adhesions in MeroGel ® -group at both 4 ( P = 0.041 ) and 12 weeks ( P < 0.001 ) . Moreover , an improvement of other endoscopic nasal findings such as re-epithelialization , presence of granulation tissue , and appearance of nasal mucosa of nasal cavities after FESS was observed in the MeroGel ® -group . Tolerability and surgical h and ling properties of MeroGel ® were positively rated by clinicians and the overall patient judged comfort of MeroGel ® was favorable . In conclusion , MeroGel ® can be considered a valid alternative to st and ard non-resorbable nasal dressings . It is safe , well-accepted , well-tolerated , and has significant advantage of being resorbable . Moreover , it may favor improved healing in patients undergoing FESS and reduce formation of adhesions Background This study investigated the efficacy of glove finger – coated polyvinyl acetate ( PA ) pack on hemostasis , pain levels , and wound healing after endoscopic sinus surgery ( ESS ) . Methods A prospect i ve , r and omized , double-blinded controlled study was performed in 30 patients who underwent bilateral ESS for chronic rhinosinusitis . Fifteen patients ( control group ) had both nasal cavities packed with PA pack ( Merocel ; Medtronic Xomed , Jacksonville , FL ) and another 15 subjects ( experimental group ) had their nasal cavities packed with PA in a glove finger . Pain levels were assessed by patients on a visual analog scale 12 hours after surgery and at the time of packing removal . The amount of bleeding on removal were quantified by weighing it after removal . Lund-Kennedy score and synechiae formation were assessed at 4 , 8 , and 12 weeks after surgery . The use of analgesics and oral steroid was compared between the two groups . Results The experimental group showed lower levels of pain and lessened bleeding during packing removal than the control group . There were no differences in pain levels at 12 hours after surgery , use of analgesics and oral steroid between the two groups . One ( 6 % ) of each group had postoperative bleeding and required additional packing for hemostasis . Lower Lund-Kennedy score at postoperative 4 weeks was documented in the experimental group . In addition , two ( 13 % ) control subjects developed a synechiae between Output:	We are unable to provide evidence to establish whether steroid-eluting sinus stents have potential advantages and disadvantages for patients with CRS undergoing FESS . Future , high- quality RCTs are needed to assess whether or not steroid-eluting sinus stents confer any beneficial effects , over those of surgery alone , when compared to non-steroid sinus stents
MS212086	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background : Fentanyl buccal soluble film ( FBSF ) has been developed as a treatment of breakthrough pain in opioid-tolerant patients with cancer . The objective of this study was to evaluate the efficacy of FBSF at doses of 200–1200 μg in the management of breakthrough pain in patients with cancer receiving ongoing opioid therapy . Patients and methods : This was a multicenter , r and omized , double-blind , placebo-controlled , multiple-crossover study that included opioid-tolerant adult patients with chronic cancer pain who experienced one to four daily episodes of breakthrough pain . The primary efficacy assessment was the sum of pain intensity differences at 30 min ( SPID30 ) postdose . Results : The intent-to-treat population consisted of 80 patients with ≥1 post-baseline efficacy assessment . The least-squares mean ( LSM ± SEM ) of the SPID30 was significantly greater for FBSF-treated episodes of breakthrough pain than for placebo-treated episodes ( 47.9 ± 3.9 versus 38.1 ± 4.3 ; P = 0.004 ) . There was statistical separation from placebo starting at 15 min up through 60 min ( last time point assessed ) . There were no unexpected adverse events ( AEs ) or clinical ly significant safety findings . Conclusions : FBSF is an effective option for control of breakthrough pain in patients receiving ongoing opioid therapy . In this study , FBSF was well tolerated in the oral cavity , with no reports of treatment-related oral AEs Purpose Instanyl ® ( intranasal fentanyl spray ) is a novel treatment for breakthrough pain ( BTP ) in cancer patients . It has shown a rapid onset of pain relief in clinical trials . This study examines the use of Instanyl ® in real-life setting s. Methods A 3-month observational , prospect i ve , cohort study of cancer patients with BTP receiving Instanyl ® ( 50 , 100 , or 200 μg ) under routine clinical practice . Data were collected at three time points corresponding with routine clinic visits – baseline , Week 4 , and Week 13 . Primary outcomes : success of titration and maintenance dose after titration . Secondary outcomes : change in maintenance dose of Instanyl ® and level of background pain medication ; Brief Pain Inventory — Short Form ( BPI-SF ) and Patient Treatment Satisfaction Scale ( PTSS ) scores ; adverse drug reactions ( ADRs ) . Results Titration with Instanyl ® was successful in 84.5 % of 309 patients ; most patients were titrated at the lowest dose ( 50 μg ) . The majority showed no change in maintenance dose , with little change in the level of background pain medication . BPI-SF and PTSS scores significantly improved from baseline to Week 4 . The main reason for terminating Instanyl ® was death , as expected due to the underlying disease ; incidence of ADRs was low and no fatal ADRs were reported . Conclusions In a real-life group of cancer patients with disease progression , Instanyl ® was titrated successfully at doses < 200 μg in the majority of patients , requiring only one dose , with no further change in maintenance dose . Pain severity , impact of pain on daily life , and treatment satisfaction significantly improved with Instanyl ® treatment . No unexpected ADRs occurred & NA ; Oral transmucosal fentanyl citrate ( OTFC ® ; Actiq ® ) is a drug delivery formulation used for management of breakthrough cancer pain . Previous studies with open‐label comparisons indicated OTFC was more effective than patients ’ usual opioid for breakthrough pain . The objective of this study was to compare OTFC and morphine sulfate immediate release ( MSIR ® ) for management of breakthrough pain in patients receiving a fixed scheduled opioid regimen . This double‐blind , double‐dummy , r and omized , multiple crossover study was conducted at 19 US university‐ and community‐based hospitals and clinics and comprised 134 adult ambulatory cancer patients . Patients were receiving a fixed scheduled opioid regimen equivalent to 60–1000 mg/day oral morphine or 50–300 & mgr;g/h transdermal fentanyl , were using a ‘ successful ’ MSIR dose ( 15–60 mg ) as defined by entry criteria , and were experiencing 1–4 episodes of breakthrough pain per day . In open‐label fashion , OTFC was titrated such that a single unit ( 200–1600 & mgr;g ) provided adequate pain relief with acceptable side effects . Successfully titrated patients entered the double‐blind phase of the study and received ten prenumbered sets of r and omized capsules and oral transmucosal units . Five sets were the successful OTFC dose paired with placebo capsules , and five sets were placebo OTFC paired with capsules containing the successful MSIR dose . Patients took one set of study medication for each episode of target breakthrough pain . Pain intensity ( PI ) , pain relief ( PR ) and global performance of medication ( GP ) scores were recorded . Pain intensity differences ( PID ) were calculated and 15‐min PID was the primary efficacy variable . Adverse events were recorded . Sixty‐nine percent of patients ( 93/134 ) found a successful dose of OTFC . OTFC yielded outcomes ( PI , PID , and PR ) at all time points that were significantly better than MSIR . GP also favored OTFC and more patients opted to continue with OTFC than MSIR following the study . Somnolence , nausea , constipation , and dizziness were the most common drug‐associated side effects . In conclusion , OTFC was more effective than MSIR in treating breakthrough cancer pain Abstract Background and objectives : Breakthrough cancer pain ( BTcP ) represents an important clinical challenge in the care of patients with cancer . This trial evaluated the efficacy and long-term tolerability of a sublingual formulation of the fast-acting opioid fentanyl , for the treatment of BTcP in opioid-tolerant patients with cancer . Research design and methods : This was a r and omized , placebo-controlled , multi-center , phase III trial , conducted in opioid-tolerant male and female patients ( aged ≥17 years ) with BTcP. The study was conducted at 36 centers across the USA . The study comprised a 2-week open-label titration phase , followed by a double-blind efficacy phase , during which patients received sublingual fentanyl citrate orally disintegrating tablet ( sublingual fentanyl ODT ) or placebo , in a r and om order . The primary efficacy endpoint was the sum of pain intensity difference ( SPID ) over 30 min post-administration . Secondary efficacy endpoints included pain intensity difference ( PID ) and pain relief ( PR ) throughout the 60-min post-dose assessment period . Following efficacy evaluation , patients entered a long-term safety phase of up to 12 months . Adverse events were recorded throughout the study . [ Clinical trial registration : NCT00262678 ] Results : A total of 131 patients entered the titration phase , of whom 61 were included in the primary efficacy analysis . Sublingual fentanyl ODT provided significant improvements in SPID relative to placebo at 30 min ( 49.5 vs. 36.6 , p = 0.0004 ) and 60 min post-administration ( 143.0 vs. 104.5 , p = 0.0002 ) . Furthermore , sublingual fentanyl ODT provided significant improvements in PID and PR compared to placebo , from 10 min post-dose ( p = 0.0055 and p = 0.049 for PID and PR , respectively ) . Patient recruitment was stopped early , due to positive interim analysis results ( significant at prespecified level , p ≤ 0.0414 ) . Overall , sublingual fentanyl ODT was well-tolerated both systemically and sublingually , with 41 patients experiencing ≥1 study drug-related adverse event ( AE ) . The most common AEs included nausea ( 12.2 % ) , vomiting ( 5.3 % ) and somnolence ( 4.6 % ) . One serious AE ( mild affect lability ) was considered possibly related to study medication . The observed pattern of AEs was consistent with that previously observed with fentanyl . Conclusions : Sublingual fentanyl ODT was efficacious and well-tolerated for the treatment of BTcP in opioid-tolerant patients with cancer . Sublingual fentanyl ODT provided significant improvements in pain intensity compared to placebo , from 10 min post-administration and throughout the 60-min post-dose assessment period . Sublingual fentanyl ODT was well tolerated over 12 months of treatment Abstract Objective : The efficacy of intranasal fentanyl spray ( INFS ) was compared with that of oral transmucosal fentanyl citrate ( OTFC ) for the relief of cancer-related breakthrough pain ( BTP ) in an open-label , crossover trial . Methods : Adult cancer patients receiving stable background opioid treatment and experiencing BTP episodes were recruited from 44 study centres in seven European countries ( Austria , France , Germany , Italy , Pol and , Spain and the United Kingdom ) ; of the 196 patients enrolled , 139 were r and omised to receive INFS followed by OTFC , or vice versa . Patients were titrated to an effective dose of one agent ( 50 , 100 or 200 µg INFS ; 200 , 400 , 600 , 800 , 1200 or 1600 µg OTFC ) to treat six BTP episodes , then titration and treatment were repeated with the other agent . The primary outcome was patient-recorded time to onset of ‘ meaningful ’ pain relief . Secondary outcomes included pain intensity difference ( PID ) at 10 and 30 minutes ( PID10 , PID30 ) , sum of PID at 15 and 60 minutes ( SPID0–15 , SPID0–60 ) , ease of administration , treatment preference and relationship between background opioid dose and effective INFS dose . Additional outcome measures included proportions of episodes with ≥33 % and ≥50 % pain intensity ( PI ) reduction , and PID at additional time points . Clinical trial registration number : NCT00496392 . Results : Among the intention-to-treat population ( n = 139 ) , median time to onset of ‘ meaningful ’ pain relief was 11 minutes with INFS versus 16 minutes with OTFC ; 65.7 % of patients attained faster time to ‘ meaningful ’ pain-relief onset with INFS ( p < 0.001 ) . PID was statistically significantly greater for INFS than OTFC from 5 minutes post-dosing . Significantly more INFS-treated breakthrough pain episodes achieved clinical ly important pain relief ( ≥33 % and ≥50 % PI reduction ) up to 30 minutes post-dosing . The proportions of episodes treated with INFS and OTFC achieving a PI reduction of ≥33 % at 5 minutes were 25.3 % versus 6.8 % ( p < 0.001 ) , and at 10 minutes were 51.0 % versus 23.6 % ( p < 0.001 ) , respectively ; the proportions of episodes treated with INFS and OTFC achieving a ≥50 % PI reduction at 5 minutes were 12.8 % versus 2.1 % ( p < 0.001 ) , and at 10 minutes were 36.9 % versus 9.7 % ( p < 0.001 ) , respectively . Higher SPID0–15 and SPID0–60 scores were achieved with INFS ( p < 0.001 ) . More patients preferred INFS than OTFC ( p < 0.001 ) and more patients found it very easy/easy to use . Both treatments were well tolerated . In the safety population ( n = 139 ) , 56.8 % ( n = 79 ) of patients experienced ≥1 AE during the trial . The only AE that occurred in ≥5 % of patients in either treatment group was nausea . Among those patients who experienced serious AEs ( 13.7 % , n = 19 ) , none were considered to be related to either study medication . There was a weak correlation between effective INFS doses and background opioid doses . Conclusion : In this open-label , r and omised , crossover trial , significantly more patients attained faster ‘ meaningful ’ pain relief with INFS than OTFC , and more patients preferred INFS to OTFC Objectives To determine the efficacy and safety of different opioids used in doses proportional to the basal opioid regimen for the management of breakthrough pain ( BP ) . Methods In 66 patients consecutive patients admitted to a pain relief and palliative care unit , the efficacy and safety of different opioids used in doses proportional to the basal opioid regimen for the management of breakthrough pain ( BP ) were assessed . The choice of the opioid to be administered as rescue medication was based on the characteristics of patients , clinical stability , compliance , preference , and so on . For each episode , nurses were instructed to routinely collect changes in pain intensity and emerging problems when pain became severe ( T0 ) , and to re-assess the patient 15 minutes after the opioid given as a rescue medication ( T15 ) . Results Six hundred twenty four episodes of BP were recorded during admission . Intravenous morphine ( IV-MO ) and oral transmucosal fentanyl ( OTFC ) were most frequently administered . Of 503 events available , 427 episodes were defined as successfully treated , while 76 episodes required a further administration of opioids . Pain intensity significantly decreased at T15 in all the groups ( P<0.001 ) Output:	Transmucosal immediate‐release fentanyl ( TIRF ) was found to have the most evidence for BtCP .
MS212087	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Access to local parks can affect walking levels . Neighborhood environment and park use may influence relationships between neighborhood socioeconomic status ( SES ) and walking . METHODS Self-report data on perceived park features , neighborhood environment , park use , neighborhood walking and sociodemographics were obtained from a sample of Australian adults , living in high/low SES areas . Surveys were mailed to 250 r and omly selected households within 500 m of 12 matched parks . Mediating effects of perceived environment attributes and park use on relationships between area-SES and walking were examined . RESULTS Mean frequency of local park use was higher for high-SES residents ( 4.36 vs 3.16 times/wk , P < .01 ) , who also reported higher levels of park safety , maintenance , attractiveness , opportunities for socialization , and neighborhood crime safety , aesthetics , and traffic safety . Safety and opportunity for socialization were independently positively related to monthly frequency of visits to a local park which , in turn , was positively associated with walking for recreation and total walking . Residents of higher SES areas reported an average 22 % ( 95 % CI : 5 % , 37 % ) more weekly minutes of recreational walking than their low SES counterparts . CONCLUSION Residents of high-SES areas live in environments that promote park use , which positively contributes to their weekly amounts of overall and recreational walking Purpose of review This review highlights recent work evaluating the relationship between exercise , physical activity and physical and mental health . Both cross-sectional and longitudinal studies , as well as r and omized clinical trials , are included . Special attention is given to physical conditions , including obesity , cancer , cardiovascular disease and sexual dysfunction . Furthermore , studies relating physical activity to depression and other mood states are review ed . The studies include diverse ethnic population s , including men and women , as well as several age groups ( e.g. adolescents , middle-aged and older adults ) . Recent findings Results of the studies continue to support a growing literature suggesting that exercise , physical activity and physical-activity interventions have beneficial effects across several physical and mental-health outcomes . Generally , participants engaging in regular physical activity display more desirable health outcomes across a variety of physical conditions . Similarly , participants in r and omized clinical trials of physical-activity interventions show better health outcomes , including better general and health-related quality of life , better functional capacity and better mood states . Summary The studies have several implication s for clinical practice and research . Most work suggests that exercise and physical activity are associated with better quality of life and health outcomes . Therefore , assessment and promotion of exercise and physical activity may be beneficial in achieving desired benefits across several population s. Several limitations were noted , particularly in research involving r and omized clinical trials . These trials tend to involve limited sample sizes with short follow-up periods , thus limiting the clinical implication s of the benefits associated with physical activity . Abbreviations CAD : coronary artery disease ; COPD : chronic obstructive pulmonary disease ; CRP : cardiac rehabilitation program ; CVD : cardiovascular disease ; GMCB : group-mediated cognitive – behavioural ; HRQOL : health-related quality of life Seasonal affective disorder ( SAD ) is a syndrome characterized by recurrent depressions that occur annually at the same time each year . We describe 29 patients with SAD ; most of them had a bipolar affective disorder , especially bipolar II , and their depressions were generally characterized by hypersomnia , overeating , and carbohydrate craving and seemed to respond to changes in climate and latitude . Sleep recordings in nine depressed patients confirmed the presence of hypersomnia and showed increased sleep latency and reduced slow-wave ( delta ) sleep . Preliminary studies in 11 patients suggest that extending the photoperiod with bright artificial light has an antidepressant effect OBJECTIVE To investigate the effects of short-term forest bathing on human health . METHODS Twenty healthy male university students participated as subjects and were r and omly divided into two groups of 10 . One group was sent on a two-night trip to a broad-leaved evergreen forest , and the other was sent to a city area . Serum cytokine levels reflecting inflammatory and stress response , indicators reflecting oxidative stress , the distribution of leukocyte subsets , and plasma endothelin-1 ( ET-1 ) concentrations were measured before and after the experiment to evaluate the positive health effects of forest environments . A profile of mood states ( POMS ) evaluation was used to assess changes in mood states . RESULTS No significant differences in the baseline values of the indicators were observed between the two groups before the experiment . Subjects exposed to the forest environment showed reduced oxidative stress and pro-inflammatory level , as evidence d by decreased malondialdehyde , interleukin-6 , and tumor necrosis factor a levels compared with the urban group . Serum cortisol levels were also lower than in the urban group . Notably , the concentration of plasma ET-1 was much lower in subjects exposed to the forest environment . The POMS evaluation showed that after exposure to the forest environment , subjects had lower scores in the negative subscales , and the score for vigor was increased . CONCLUSION Forest bathing is beneficial to human health , perhaps through preventive effects related to several pathological factors Background : Green , natural environments may ameliorate adverse environmental exposures ( e.g. , air pollution , noise , and extreme heat ) , increase physical activity and social engagement , and lower stress . Objectives : We aim ed to examine the prospect i ve association between residential greenness and mortality . Methods : Using data from the U.S.-based Nurses ’ Health Study prospect i ve cohort , we defined cumulative average time-varying seasonal greenness surrounding each participant ’s address using satellite imagery [ Normalized Difference Vegetation Index ( NDVI ) ] . We followed 108,630 women and observed 8,604 deaths between 2000 and 2008 . Results : In models adjusted for mortality risk factors ( age , race/ethnicity , smoking , and individual- and area-level socioeconomic status ) , women living in the highest quintile of cumulative average greenness ( accounting for changes in residence during follow-up ) in the 250-m area around their home had a 12 % lower rate of all-cause nonaccidental mortality [ 95 % confidence interval ( CI ) ; 0.82 , 0.94 ] than those in the lowest quintile . The results were consistent for the 1,250-m area , although the relationship was slightly attenuated . These associations were strongest for respiratory and cancer mortality . The findings from a mediation analysis suggested that the association between greenness and mortality may be at least partly mediated by physical activity , particulate matter < 2.5 μm , social engagement , and depression . Conclusions : Higher levels of green vegetation were associated with decreased mortality . Policies to increase vegetation may provide opportunities for physical activity , reduce harmful exposures , increase social engagement , and improve mental health . Planting vegetation may mitigate the effects of climate change ; in addition , evidence of an association between vegetation and lower mortality rates suggests it also might be used to improve health . Citation : James P , Hart JE , Banay RF , Laden F. 2016 . Exposure to greenness and mortality in a nationwide prospect i ve cohort study of women . Environ Health Perspect 124:1344–1352 ; Forest bathing trip is a short , leisurely visit to forest . In this study we determined the health effects of forest bathing trip on elderly patients with chronic obstructive pulmonary disease ( COPD ) . The patients were r and omly divided into two groups . One group was sent to forest , and the other was sent to an urban area as control . Flow cytometry , ELISA , and profile of mood states ( POMS ) evaluation were performed . In the forest group , we found a significant decrease of perforin and granzyme B expressions , accompanied by decreased levels of pro-inflammatory cytokines and stress hormones . Meanwhile , the scores in the negative subscales of POMS decreased after forest bathing trip . These results indicate that forest bathing trip has health effect on elderly COPD patients by reducing inflammation and stress level We previously reported that the forest environment enhanced human natural killer ( NK ) cell activity , the number of NK cells , and intracellular anti-cancer proteins in lymphocytes , and that the increased NK activity lasted for more than 7 days after trips to forests both in male and female subjects . To explore the factors in the forest environment that activated human NK cells , in the present study we investigate the effect of essential oils from trees on human immune function in twelve healthy male subjects , age 37–60 years , who stayed at an urban hotel for 3 nights from 7.00p.m . to 8.00a.m . Aromatic volatile substances ( phytoncides ) were produced by vaporizing Chamaecyparis obtusa ( hinoki cypress ) stem oil with a humidifier in the hotel room during the night stay . Blood sample s were taken on the last day and urine sample s were analysed every day during the stay . NK activity , the percentages of NK and T cells , and granulysin , perforin , granzyme A/B-expressing lymphocytes in blood , and the concentrations of adrenaline and noradrenaline in urine were measured . Similar control measurements were made before the stay on a normal working day . The concentrations of phytoncides in the hotel room air were measured . Phytoncide exposure significantly increased NK activity and the percentages of NK , perforin , granulysin , and granzyme A/B-expressing cells , and significantly decreased the percentage of T cells , and the concentrations of adrenaline and noradrenaline in urine . Phytoncides , such as α-pinene and β-pinene , were detected in the hotel room air . These findings indicate that phytoncide exposure and decreased stress hormone levels may partially contribute to increased NK activity Output:	Incidence of stroke , hypertension , dyslipidaemia , asthma , and coronary heart disease were reduced . Conclusions : Greenspace exposure is associated with numerous health benefits in intervention and observational studies . These results are indicative of a beneficial influence of greenspace on a wide range of health outcomes . Green prescriptions involving greenspace use may have substantial benefits . HighlightsGreenspace exposure is associated with wide ranging health benefits across 143 included studies .Meta‐ analysis showed statistically significant reductions in diastolic blood pressure , salivary cortisol and heart rate . Meta‐ analysis found statistically significant decreases in incidence of diabetes , all‐cause and cardiovascular mortality .
MS212088	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective To compare 1-year cure rates after laparoscopic Burch colposuspension using one double-bite or two single-bite sutures on each side of the urethra . Methods Consecutive women with primary stress urinary incontinence at one university hospital were included . Pre-operative clinical and urodynamic evaluation included cystoscopy , cystouretrometry at rest and stress , and a st and ardized pad test . Immediately before surgery , the patients were r and omized to have one or two polytetrafluoroethylene ( GoreTex CV 2 ; W. L. Gore Inc. , Flagstaff , AZ ) sutures placed on each side of the urethra . During surgery , access to the space of Retzius was achieved by transperitoneal videolaparoscopic technique . Women were scheduled for postoperative interview and pad test 1 year after surgery . Results We included 161 women in the study ; 78 were r and omized to one suture ( group A ) and 83 to two sutures ( group B ) . Median time for surgery was significantly shorter for group A than for group B ( 60 compared with 77 minutes ; P < .001 ) . We examined 158 women 1 year after surgery , at which time 148 performed a pad test . Objective cure rate was significantly higher in group B than in group A ( 83 % compared with 58 % ; P = .001 ) . Conclusion Two single-bite sutures result ed in a significantly higher objective short-term cure rate than one double-bite suture on each side of the urethra Introduction and hypothesisThe aim of this study is to provide long-term outcome data , at least 10 years , following laparoscopic colposuspension . Methods The study includes a control group who underwent open colposuspension . A consecutive series of 139 women who had undergone laparoscopic colposuspension were review ed and compared to 52 women who had an open colposuspension in the same unit . Subjects were contacted by telephone , at least 10 years post-operatively , at which time a structured interview was performed which included the short-form Bristol Female Lower Urinary Tract Symptom question naire . Results There was deterioration in subjective cure rates from 71 % and 67 % at 6 months to 52 % and 36 % at 10 years for the laparoscopic and open procedures , respectively . Conclusion This study provides evidence that laparoscopic colposuspension is probably as durable as open colposuspension . However , cure rates for both procedures appear to deteriorate over time , emphasising the importance of long-term follow-up Background . Evaluation of cost‐effectiveness of new surgical techniques is important . As the data on incontinence procedures are scarce , we evaluated the cost‐effectiveness of tension‐free vaginal tape procedure and laparoscopic mesh colposuspension as a primary surgical treatment for female stress urinary incontinence . Methods . In four university teaching hospitals and two central hospitals 128 stress incontinent women were r and omized to tension‐free vaginal tape procedure ( n = 70 ) or laparoscopic mesh colposuspension ( n = 51 ) in order to investigate the clinical performance of these two procedures . Primary objective clinical outcome measures were : stress test and 48‐h pad test . Secondary subjective outcome measures were health‐related quality of life measured in terms of visual analogue scale and Urinary Incontinence Severity Score . Alongside the clinical trial , a cost‐effectiveness analysis for the main outcome measures was performed . Results . The changes in the 48‐h pad test result did not reach statistical significance ( p = 0.105 ) . When the visual analogue scale or Urinary Incontinence Severity Score are used as the outcome measure , the tension‐free vaginal tape is more cost‐effective than laparoscopic mesh colposuspension over a follow‐up period of one year ( p<0.000 ) . Conclusion . The clinical and economic data of the present study suggest that over a follow‐up period of one year the tension‐free vaginal tape procedure is more cost‐effective than laparoscopic mesh colposuspension as a primary treatment for female stress urinary incontinence Background . The aim of this study was to compare laparoscopic colposuspension with tension‐free vaginal tape ( TVT ) in terms of costs to the county Objective : We compared the success of laparoscopic Burch colposuspension with the laparotomic Burch colposuspension for the treatment of genuine stress incontinence ( GSI ) concomitant with gynecologic operations . Material s and Methods : Fifty-two women with symptoms of GSI , also requiring additional gynecologic operations , were r and omly assigned to undergo laparoscopic ( n = 26 ) or laparotomic ( n = 26 ) Burch colposuspension . For all patients complete histories were taken and physical examination , urinalysis , urine culture , multi-channel urodynamics with cystometry , uroflowmetry , and measurement of Valsalva leak-point pressure were performed . Variables analyzed included : age , surgical time , length of catheterization , number of days in hospital , and complications . Results : Both groups were similar in age , parity and menopausal status . Valsalva leak-point pressure significantly increased in the laparoscopy group after the operation . There were no statistical differences in other urodynamics in both groups . The mean operating time in the laparoscopy group was longer than in the laparotomy group . The laparoscopy group required a significantly shorter hospitalization and catheterization than the laparotomy group . The success and complication rates did not differ significantly for both groups . Conclusion : The laparoscopic approach for the treatment of GSI in patients requiring additional gynecologic procedures is associated with a shorter duration of hospital stay compared with the abdominal approach OBJECTIVE To compare the efficacy , safety , complications , and short-term outcome of laparoscopic and open colposuspension in women with genuine stress incontinence . DESIGN R and omised controlled trial . SETTING Urogynaecology unit in a public hospital , Hong Kong . SUBJECTS AND METHODS Ninety patients with urodynamically proven genuine stress incontinence . Forty-three patients were r and omly allocated to receive open colposuspension and 47 to undergo laparoscopy . All patients had re assessment within 1 year of the operation . MAIN OUTCOME MEASURES Objective and subjective measures and complication rates . RESULTS There was no significant difference in the duration of stress incontinence , mean preoperative pad test results , or proportion with pre-existing detrusor instability . Among patients in the laparoscopic group , the mean operating time was significantly longer ( 42.0 minutes versus 29.3 minutes ; P<0.0001 ) , while the mean blood loss was significantly less ( 124.7 mL versus 326.9 mL ; P=0.001 ) . Subjective and objective success rates within 1 year were similar for patients in the open and laparoscopic groups ( 86.0 % versus 80.9 % ; P=0.58 , and 86.0 % versus 85.1 % ; P=1.00 , respectively ) . There was no significant difference in the rate of complications , including de novo detrusor instability and an obstructive voiding pattern , enterocele , or dyspareunia . CONCLUSION Laparoscopic colposuspension is a feasible alternative to the open approach . The operating time is longer but the short-term cure rate is comparable with that of the open approach The technical feasibility of the laparoscopic and extraperitoneal approach to the Burch colposuspension for treatment of grade II and III ( moderate to severe ) stress incontinence was examined in a r and omised prospect i ve study . Irrespective of the endoscopic access , two suspension techniques , namely conventional suture and stapler fixation of alloplastic material s , were compared . A total of 20 patients entered this preliminary evaluation . Three complications occurred ; a bladder perforation ( during laparoscopic dissection of the space of Retzius ) , a postoperative detrusor instability and transient urinary retention . Both the endoscopic approaches and the suspension procedures employed proved feasible and safe , and presented the advantages of a " minimal access " procedure , with short hospitalisation and rapid recovery . Short-term follow-up ( 6 - 12 months ) showed subjective and objective results comparable to those of the conventional abdominal Burch colposuspension . Detailed evaluation of the subgroups is not yet feasible , as the number of patients in this preliminary evaluation was too small and follow-up too short . Final evaluation of the entire study population and long-term follow-up will be necessary before these procedures can be generally offered as a therapeutic alternative OBJECTIVE : To estimate costs for incontinence management , health-related quality of life , and willingness to pay for incontinence improvement in women electing surgery for stress urinary incontinence . METHODS : A total of 655 incontinent women enrolled in the Stress Incontinence Surgical Treatment Efficacy Trial , a r and omized surgical trial . Baseline out-of-pocket costs for incontinence management were calculated by multiplying self-report of re sources used ( supplies , laundry , dry cleaning ) by national re source costs ( $ 2006 ) . Health-related quality of life was estimated with the Health Utilities Index Mark 3 . Participants estimated willingness to pay for 100 % improvement in incontinence . Potential predictors of these outcomes were examined by using multivariable linear regression . RESULTS : Mean age was 52±10 years , and mean number of weekly incontinence episodes was 22±21 . Mean and median ( 25 % , 75 % interquartile range ) estimated personal costs for incontinence management among all women were $ 14±$24 and $ 8 ( interquartile range $ 3 , $ 18 ) per week , and 617 ( 94 % ) women reported any cost . Costs increased significantly with incontinence frequency and mixed compared with stress incontinence . The mean and median Health Utilities Index Mark 3 scores were 0.73±0.25 and 0.84 ( interquartile range 0.63 , 0.92 ) . Women were willing to pay a mean of $ 118±$132 per month for complete resolution of incontinence , and willingness to pay increased significantly with greater expected incontinence improvement , household income , and incontinent episode frequency . CONCLUSION : Urinary incontinence is associated with substantial costs . Women spent nearly $ 750 per year out of pocket for incontinence management , had a significant decrement in quality of life , and were willing to pay nearly $ 1,400 per year for cure . LEVEL OF EVIDENCE : STUDY OBJECTIVE To compare laparoscopic Burch colposuspension and tension-free vaginal tape ( TVT ) procedure in women with genuine stress incontinence . DESIGN R and omized clinical study ( Canadian Task Force classification I ) . SETTING Tertiary care university hospital . PATIENTS Forty-six consecutive women . INTERVENTION Laparoscopic Burch colposuspension ( 23 ) and TVT procedure ( 23 ) . MEASUREMENTS AND MAIN RESULTS Valsalva leak-point pressure increased after surgery in both groups , but TVT substantially decreased maximum urinary flow rate . Other urodynamic studies showed no statistical differences . The groups did not differ significantly with respect to intraoperative complications or objective and subjective cure rates . Operating time was significantly longer for laparoscopic Burch ( p = 0.001 ) , and three patients in that group required conversion to laparotomy . Length of hospital stay ( p = 0.003 ) and duration of catheterization ( p = 0.003 ) were shorter in the TVT group . CONCLUSION TVT holds promise in women with genuine stress incontinence , with several advantages over laparoscopic Burch Introduction and hypothesisBefore the introduction of the tension-free vaginal tape ( TVT ) procedure for the treatment of female stress urinary incontinence , the colposuspension operation was regarded as the “ gold st and ard ” procedure . The laparoscopic variant of the colposuspension was introduced as a less invasive operation . The aim of the present trial was to compare the new minimally invasive TVT procedure with laparoscopic mesh colposuspension ( LCM ) . Methods A multicenter r and omized clinical trial conducted in six public hospitals in Finl and including primary cases of stress incontinence . Objective treatment success criteria were a negative stress test and no retreatment for stress incontinence . Patient satisfaction was assessed by Patients Global Impression of Improvement , a visual analog scale , and the Urinary Incontinence Severity Score . Results Of 128 r and omized patients , 121 underwent the allocated operation . At the 5-year follow-up 77 % in the TVT group and 84 % in the LCM group could be assessed according to the protocol . The objective cure rate was significantly higher in the TVT group ( 94 % ) than in the LCM group ( 78 % ) . Subjective treatment satisfaction ( completely satisfied with the procedure ) was significantly higher in the TVT group ( 64 % ) than in the LCM group ( 51 % ) . Conclusions By per protocol analysis both objective and subjective cure rates were significantly higher in the TVT group than in the LCM group . If cases that were lost to follow-up were regarded as failures , the intension-to-treat analysis found no difference between the groups STUDY OBJECTIVE To compare results of laparoscopic Burch colposuspension with those of classic Burch colposuspension , and to assess complications , results , and morbidity associated with each procedure . DESIGN Prospect i ve , r and om Output:	Whilst the women 's subjective impression of cure seemed similar for both procedures , in the short- and medium-term follow-up , there was some evidence of poorer results of laparoscopic colposuspension on objective outcomes . The results showed trends towards fewer perioperative complications , less postoperative pain and shorter hospital stay for laparoscopic compared with open colposuspension , however , laparoscopic colposuspension was more costly . We observed no significant differences for postoperative voiding dysfunction and perioperative complications . Laparoscopic colposuspension had a significantly longer operation time and hospital stay . Currently available evidence suggests that laparoscopic colposuspension may be as good as open colposuspension at two years post surgery . However , the newer vaginal sling procedures appear to offer even greater benefits , better objective outcomes in the short term and similar subjective outcomes in the longer term . If laparoscopic colposuspension is performed , the use of two paravaginal sutures appears to be the most effective method .
MS212089	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: In this prospect i ve r and omised study two treatments after non-traumatic medial meniscal tear diagnosed with radiological examination and magnetic resonance imaging were compared ; arthroscopic partial meniscectomy followed by supervised exercise or supervised exercise alone . The aim was to evaluate knee function and physical activity . Ninety patients ( mean age 56 years ) were evaluated using the Knee Injury and Osteoarthritis Outcome Score , the Lysholm Knee Scoring Scale , the Tegner Activity Scale and a Visual Analogue Scale for knee pain prior to the intervention , after 8 weeks of exercise and after 6 months . According to the outcome scores arthroscopic partial medial meniscectomy combined with exercise did not lead to greater improvement than exercise alone . After the intervention both groups reported decreased knee pain , improved knee function and a high satisfaction ( P < 0.0001 ) . Forty-one per cent of the patients returned to their pre-injury activity level after 6 months . In conclusion , when evaluated with outcome scores , arthroscopic partial medial meniscectomy followed by supervised exercise was not superior to supervised exercise alone in terms of reduced knee pain , improved knee function and improved quality of life Background — Arthroscopic meniscal surgery is the most common orthopedic procedure , and the incidence has increased in Denmark over the last 10 years . Concomitantly , several r and omized controlled trials have shown no benefit of arthroscopic procedures including arthroscopic partial meniscectomy in middle-aged and older individuals suffering from knee pain with or without knee osteoarthritis . We examined the annual incidence of meniscal procedures together with age , sex , and diagnosis for patients who underwent meniscal procedures in the period 2000–2011 in Denmark . Methods — Data on age , sex , diagnosis , and surgical procedures were extracted from the Danish National Patient Register for the years 2000–2011 , for all records containing meniscal surgery as a primary or secondary procedure . Results — The overall annual incidence of meniscal procedures per 100,000 persons in Denmark doubled from 164 in 2000 to 312 in 2011 ( i.e. 8,750 procedures to 17,368 procedures ) . A 2-fold increase was found for patients aged between 35 and 55 , and a 3-fold increase was found for those older than 55 . Middle-aged and older patients accounted for 75 % of all 151,228 meniscal procedures carried out between 2000 and 2011 . Interpretation — The incidence of meniscal procedures performed in Denmark doubled from 2000 to 2011 , with the largest increase in middle-aged and older patients . This increase contrasts with the mounting evidence showing no added benefit of arthroscopic partial meniscectomy over non-surgical treatments . Our observations illustrate the long delay in the dissemination , acceptance , and implementation of research evidence into the practice of arthroscopic surgery PURPOSE To determine whether preoperative magnetic resonance ( MR ) imaging could help identify factors associated with poor clinical outcome after arthroscopic partial meniscectomy ( APM ) in middle-aged and elderly patients with meniscal tears . MATERIAL S AND METHODS The prospect i ve , institutional review board-approved , HIPAA-compliant study was performed with informed consent in 53 men and 47 women ( average ages , 54.5 and 56.6 years , respectively ) . Patients underwent knee MR imaging before APM ; clinical symptoms were evaluated preoperatively and 1 year postoperatively with International Knee Documentation Committee ( IKDC ) question naire . Overall severity of knee joint degeneration and severity of each feature of joint degeneration were assessed with Boston Leads Osteoarthritis Knee ( BLOK ) scoring system . Tear length was measured , and type of meniscal tear was classified . Spearman correlation coefficients and relative risks showed the relationship between clinical outcome after APM ( difference between preoperative and postoperative IKDC scores ) and severity of joint degeneration . RESULTS Seventy-four patients with isolated medial APM had a significant ( P < .05 ) inverse correlation between clinical outcome and severity of cartilage loss and bone marrow edema in the medial femoral condyle and medial tibial plateau . Fifteen patients with isolated lateral APM had a significant ( P < .05 ) inverse correlation between clinical outcome and severity of cartilage loss in the lateral femoral condyle and lateral tibial plateau and bone marrow edema in the lateral femoral condyle . One hundred patients with APM had a significant ( P < .05 ) inverse correlation between clinical outcome and severity of meniscal extrusion , total BLOK score , and meniscal tear length . A significantly ( P < .05 ) increased relative risk that a patient would not definitely improve after APM was observed if a meniscal root tear was present . CONCLUSION Poorer clinical outcome after APM was associated with greater severity of cartilage loss and bone marrow edema in the same compartment as the meniscal tear , greater severity of meniscal extrusion , greater overall severity of joint degeneration , a meniscal root tear , and a longer meniscal tear at preoperative MR imaging Introduction Arthroscopic partial meniscectomy ( APM ) to treat degenerative meniscus injury is the most common orthopaedic procedure . However , valid evidence of the efficacy of APM is lacking . Controlling for the placebo effect of any medical intervention is important , but seems particularly pertinent for the assessment of APM , as the symptoms commonly attributed to a degenerative meniscal injury ( medial joint line symptoms and perceived disability ) are subjective and display considerable fluctuation , and accordingly difficult to gauge objective ly . Methods and analysis A multicentre , parallel r and omised , placebo surgery controlled trial is being carried out to assess the efficacy of APM for patients from 35 to 65 years of age with a degenerative meniscus injury . Patients with degenerative medial meniscus tear and medial joint line symptoms , without clinical or radiographic osteoarthritis of the index knee , were enrolled and then r and omly assigned ( 1 : 1 ) to either APM or diagnostic arthroscopy ( placebo surgery ) . Patients are followed up for 12 months . According to the prior power calculation , 140 patients were r and omised . The two r and omised patient groups will be compared at 12 months with intention-to-treat analysis . To safeguard against bias , patients , healthcare providers , data collectors , data analysts , outcome adjudicators and the research ers interpreting the findings will be blind to the patients ’ interventions ( APM/placebo ) . Primary outcomes are Lysholm knee score ( a generic knee instrument ) , knee pain ( using a numerical rating scale ) , and WOMET score ( a disease-specific , health-related quality of life index ) . The secondary outcome is 15D ( a generic quality of life instrument ) . Further , in one of the five centres recruiting patients for the r and omised controlled trial ( RCT ) , all patients scheduled for knee arthroscopy due to a degenerative meniscus injury are prospect ively followed up using the same protocol as in the RCT to provide an external validation cohort . In this article , we present and discuss our study design , focusing particularly on the internal and external validity of our trial and the ethics of carrying out a placebo surgery controlled trial . Ethics and dissemination The protocol has been approved by the institutional review board of the Pirkanmaa Hospital District and the trial has been duly registered at Clinical Trials.gov . The findings of this study will be disseminated widely through peer- review ed publications and conference presentations . Trial registration Clinical Trials.gov , number NCT00549172 OBJECTIVE To determine if visually-guided arthroscopic irrigation is an effective therapeutic intervention in patients with early knee osteoarthritis . DESIGN Ninety patients with knee osteoarthritis were r and omized in a double-blind fashion to receive either arthroscopic irrigation with 3000 ml of saline ( treatment group ) or the minimal amount of irrigation ( 250 ml ) required to perform arthroscopy ( placebo group ) . The primary outcome variable was aggregate WOMAC score . RESULTS The study did not demonstrate an effect of irrigation on arthritis severity as measured by aggregate WOMAC scores , the primary outcome variable ; the mean change in aggregate WOMAC score at 12 months was 15.5 ( 95 % CI 7.7 , 23.4 ) for the full irrigation group compared to 8.9 ( 95 % CI 4.9 , 13.0 ) for the minimal irrigation group ( P=0.10 ) . Full irrigation did have a statistically significant effect on patients ' self-reported pain as measured by the WOMAC pain subscale and by a visual analog scale ( VAS ) ( the secondary outcome variables ) . Mean change in WOMAC pain scores decreased by 4.2 ( 95 % CI -0.9 , 9.4 ) for the full irrigation group compared with a mean decrease of 2.3 ( 95 % CI -0.1 , 4.7 ) in the minimal irrigation group ( P=0.04 ) . Mean VAS pain scores decreased by 1.47 ( 95 % CI -1.2 , 4.1 ) in the full irrigation group compared to a mean decrease of 0.12 ( 95 % CI 0.0 , 0.3 ) in the minimal irrigation group ( P=0.02 ) . A hypothesis-generating post-hoc analysis of the effect of positively birefrigent intraarticular crystals showed that patients with and without intraarticular crystals had statistically significant improvements in pain assessment s and aggregate WOMAC scores at 12 months ; patients with crystals had statistically greater improvements in pain . CONCLUSIONS Visually-guided arthroscopic irrigation may be a useful therapeutic option for relief of pain in a subset of patients with knee OA , particularly in those who have occult intraarticular crystals Background : It is still debated whether a degenerative horizontal tear of the medial meniscus should be treated with surgery . Hypothesis : The clinical outcomes of arthroscopic meniscectomy will be better than those of nonoperative treatment for a degenerative horizontal tear of the medial meniscus . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : A total of 102 patients with knee pain and a degenerative horizontal tear of the posterior horn of the medial meniscus on magnetic resonance imaging were included in this study between January 2007 and July 2009 . The study included 81 female and 21 male patients with an average age of 53.8 years ( range , 43 - 62 years ) . Fifty patients underwent arthroscopic meniscectomy ( meniscectomy group ) , and 52 patients underwent nonoperative treatment with strengthening exercises ( nonoperative group ) . Functional outcomes were compared using a visual analog scale ( VAS ) for pain , Lysholm knee score , Tegner activity scale , and patient subjective knee pain and satisfaction . Radiological evaluations were performed using the Kellgren-Lawrence classification to evaluate osteoarthritic changes . Results : In terms of clinical outcomes , meniscectomy did not provide better functional improvement than nonoperative treatment . At the final follow-up , the average VAS scores were 1.8 ( range , 1 - 5 ) in the meniscectomy group and 1.7 ( range , 1 - 4 ) in the nonoperative group ( P = .675 ) . The average Lysholm knee scores at 2-year follow-up were 83.2 ( range , 52 - 100 ) and 84.3 ( range , 58 - 100 ) in the meniscectomy and nonoperative groups , respectively ( P = .237 ) . In addition , the average Tegner activity scale and subjective satisfaction scores were not significantly different between the 2 groups . Although most patients initially had intense knee pain with mechanical symptoms , both groups reported a relief in knee pain , improved knee function , and a high level of satisfaction with treatment ( P < .05 for all values ) . Two patients in the meniscectomy group and 3 in the nonoperative group with Kellgren-Lawrence grade 1 progressed to grade 2 at the 2-year follow-up . Conclusion : There were no significant differences between arthroscopic meniscectomy and nonoperative management with strengthening exercises in terms of relief in knee pain , improved knee function , or increased satisfaction in patients after 2 years of follow-up OBJECTIVES Patients with knee osteoarthritis ( OA ) often suffer pain that is not fully controlled by analgesics and often require intra-articular therapies . The aim of this study was to compare the benefits of intra-articular corticosteroid injections ( CSIs ) and tidal irrigation ( TI ) in patients with OA of the knee . METHODS We performed a dual-centre , single blind , r and omised , parallel group trial comparing TI and CSI . Patients with knee OA were r and omised to either irrigation using a 3.2 mm arthroscope under local anaesthesia or an intra-articular injection of 40 mg triamcinolone acetonide and 1 % lidocaine . Patients were followed for 6 months . The primary outcome measure was the Western Ontario and McMaster Universities OA Index total pain score ( visual analogue scale , VAS ) . RESULTS One hundred and fifty patients were recruited of whom 71 received TI and 79 CSI . In both treatment groups , over 80 % of patients reported improvement at 2 and 4 weeks . After this time , the benefit of CSI decreased whereas that of TI was maintained : at 26 weeks the Output:	There was no difference in the side effects between patients with AT and the control group . AT in OA patients is not useless because there is evidence that a subgroup of patients with non-traumatic flap tears of the medial meniscus or patients with crystal arthropathy benefit from arthroscopy .
MS212090	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: We studied which physiological and kinanthropometric characteristics determine climbing performance in 16 high-level sports climbers aged 29.9 ± 4.9 years . Body composition parameters were measured with dual energy X-ray absorptiometry scanner . We also measured kinanthropometric and physical fitness parameters . The sex-specific 75th percentile value of onsight climbing ability was used to divide the sample into expert ( < 75th ) and elite ( ≥75th ) climbers . All the analyses were adjusted by sex . The 75th percentile value of onsight climbing ability was 7b in women and 8b in men . There were no differences between expert and elite climbers in the studied variables , except in climbing time to exhaustion and bone mineral density . Elite climbers had a significantly higher time to exhaustion than the expert group ( 770.2 ± 385 vs. 407.7 ± 150 s , respectively , P = 0.001 ) . These results suggest that , among climbers with a high level of performance , as those analysed in this study , climbing time to exhaustion is a major determinant of climbing performance White , DJ and Olsen , PD . A time motion analysis of bouldering style competitive rock climbing . J Strength Cond Res 24(5 ) : 1356 - 1360 , 2010-Limited research has been performed on competitive bouldering . The aim of this study was to quantify the movement dynamics of elite boulder climbers . Six climbers were filmed during a national competition consisting of 5 novel climbing problems or routes . Two problems were r and omly selected and film footage was analyzed using K and le Swinger Pro software to determine type and duration ( seconds ) of bouldering movements . All subjects provided consent , and the study had ethical approval . The mean ± SD were determined for number of attempts per problem , duration of attempt , time on hold , and time to reach between holds . Exercise : recovery ratios were also calculated . On average , climbers attempted a problem 3.0 ± 0.5 times , with an attempt lasting 28.9 ± 10.8 seconds and rest periods of 114 ± 31 seconds between attempts . Average time gripping holds was 7.9 ± 1.3 seconds , with approximately 0.5 ± 0.1 seconds recovery between reaching for holds . The exercise-to-recovery ratio was ∼1:4 for attempting a problem and ∼13:1 for forearm muscles during climbing . The exercise-to-recovery ratios allow sufficient time for recovery during and after a problem . However , the prolonged contraction of forearm muscles indicates the importance of strength and endurance in these muscles . Video analysis was found to be a useful tool for the quantification of movement characteristics of competitive elite boulders . Data collected could be utilized in the design of sport-specific tests and training programs . Future research could examine a larger number of athletes and problems and help develop performance tests and training interventions for bouldering OBJECTIVES To assess oxygen uptake ( VO2 ) , blood lactate concentration ( [ La(b ) ] ) , and heart rate ( HR ) response during indoor and outdoor sport climbing . METHODS Seven climbers aged 25 ( SE 1 ) years , with a personal best ascent without p review or fall ( on sight ) ranging from 6b to 7a were assessed using an indoor vertical treadmill with artificial rock h and /foot holds and a discontinuous protocol with climbing velocity incremented until voluntary fatigue . On a separate occasion the subjects performed a 23.4 m outdoor rock climb grade d 5c and taking 7 min 36 s ( SE 33 s ) to complete . Cardiorespiratory parameters were measured using a telemetry system and [ La(b ) ] collected at rest and after climbing . RESULTS Indoor climbing elicited a peak oxygen uptake ( VO2climb-peak ) and peak HR ( HRpeak ) of 43.8 ( SE 2.2 ) ml/kg/min and 190 ( SE 4 ) bpm , respectively and increased blood lactate concentration [ La(b ) ] from 1.4 ( 0.1 ) to 10.2 ( 0.6 ) mmol/l ( p < 0.05 ) . During outdoor climbing VO2 and HR increased to about 75 % and 83 % of VO2climb-peak and HRpeak , respectively . [ La(b ) ] increased from 1.3 ( 0.1 ) at rest to 4.5 mmol/l ( p < 0.05 ) at 2 min 32 s ( 8 s ) after completion of the climb . CONCLUSIONS The results suggest that for elite climbers outdoor sport rock climbs of five to 10 minutes ' duration and moderate difficulty require a significant portion of the VO2climb-peak . The higher HR and VO2 for outdoor climbing and the increased [ La(b ) ] could be the result of repeated isometric contractions , particularly from the arm and forearm muscles Abstract Medernach , JPJ , Kleinöder , H , Lötzerich , HHH . Fingerboard in competitive bouldering : Training effects on grip strength and endurance . J Strength Cond Res 29(8 ) : 2286–2295 , 2015—Bouldering ( BL ) is an independent discipline of sport climbing , with grip strength and endurance as key factors . Although the sport has grown increasingly popular and competitive , limited research has been conducted on commonly used training methods to maximize BL performance . The purpose of this study was to investigate the training effects of 4 weeks of fingerboarding ( FB ) on grip strength and endurance in competitive BL . Twenty-three highly advanced male boulderers ( 25.6 ± 4.4 y ; 1.78 ± 0.05 m ; 70.1 ± 5.4 kg ; 6.2 ± 2.8 y climbing ; 7b+ Fb mean ability ) were r and omly allocated to a 4-week FB ( n = 11 ) or BL ( n = 12 ) training regimen . Pretests and posttests ( 50-min duration ) involved ( a ) h and held dynamometry ( GS ) to assess grip strength , ( b ) dead hangs ( DH ) , and ( c ) intermittent finger hangs ( IFH ) to assess grip endurance . After the 4-week regimen , GS increased significantly in the FB group ( 2.5 ± 1.4 kg , p < 0.001 ) but not in the BL group ( 1.4 ± 2.8 kg , p = 0.109 ) . The mean increase in DH ranged from 5.4 to 6.7 seconds in the FB group and was significantly ( p ⩽ 0.05 ) higher than that in the BL group ( 3.0–3.9 seconds ) . Finally , significantly higher IFH gains were observed in the FB group ( p = 0.004 ) , with a mean gain of 26 seconds , but not in the BL group ( p = 0.168 ) . These results suggest that FB is highly effective in increasing grip strength and endurance in competitive BL Performing intra-session recovery is important in rock climbing due to the multiple efforts that climbers are required to make in competitions , as well as repeated climbing trials that they carry out during training sessions . Active recovery has been shown to be a better option than passive recovery . However , the type of active recovery that should be done and the influence of the type and quantity of muscle mass activated are not clear . The aim of this study was to compare the effects of recovering with easy climbing ( CR ) or walking ( WR ) on markers of fatigue and climbing performance . For this purpose , 14 subjects participated in this r and omly assigned crossover protocol completing three two-minute climbing trials separated by two minutes of active recovery with the assigned method . Seven days later participants carried out the same protocol with the other recovery method . Blood lactate ( La(- ) ) , rating of perceived exertion ( RPE ) , and heart rate ( HR ) were analyzed as markers of fatigue and recovery , while meters climbed ( MC ) and h and grip force ( HF ) were analyzed for performance . La- values before the last climbing trial ( p < 0.05 ; d = 0.69 ) and Peak La- values ( p < 0.05 ; d = 0.77 ) were lower for CR than for WR . Climbers were able to ascend more meters in the set time when following the CR protocol ( p < 0.01 ; d = 0.6 ) , which shows the important role of the active recovery method carried out on climbing performance . There were no differences in HR , HF or RPE between protocol s. A more sport-specific recovery protocol , in addition to moving great muscle mass ( e.g. lower limbs ) , seems to enhance recovery and to facilitate lactate removal . For this reason , CR appears to be a more effective active recovery method than WR in sport rock climbing . Key pointsClimbing recovery improved lactate removal in comparison with walking recovery . Subjects were able to climb more meters in a determined time when easy climbing instead of walking during recoveries . Activating both great muscle mass like that of the lower limbs as well as the main fatigue producing muscles ( forearms in climbing ) seems more effective for recovering than activating just great muscle mass One of the main objectives of the experiment reported in this article was to analyze the arrangement of the forces applied to the holds accompanying a voluntary right foot release in the hanging rock climber . The three dimensional reaction forces applied to the holds were measured using four holds equipped with strain gauges . The force arrangement after the release consisted of a tripedal stance on the three remaining holds for the vertical forces , and of a bipedal stance on two laterally opposite holds ( left foot and left holds ) for the horizontal forces . The general significance of the results was analyzed with respect to the mechanism of static equilibrium . However , before conclusions can be drawn , other climbing movements and positions must be analyzed There is limited information on the anthropometry , strength , endurance and flexibility of female rock climbers . The aim of this study was to compare these characteristics in three groups of females : Group 1 comprised 10 elite climbers aged 31.3 ± 5.0 years ( mean ± s ) who had led to a st and ard of ‘ hard very severe ’ ; Group 2 consisted of 10 recreational climbers aged 24.1 ± 4.0 years who had led to a st and ard of ‘ ; severe ’ ; and Group 3 comprised 10 physically active individuals aged 28.5 ± 5.0 years who had not previously rock-climbed . The tests included finger strength ( grip strength , finger strength measured on climbing-specific apparatus ) , flexibility , bent arm hang and pull-ups . Regression procedures ( analysis of covariance ) were used to examine the influence of body mass , leg length , height and age . For finger strength , the elite climbers recorded significantly higher values ( P < 0.05 ) than the recreational climbers and non-climbers ( four fingers , right h and : elite 321 ± 18 N , recreational 251 ± 14 N , non-climbers 256 ± 15 N ; four fingers , left h and : elite 307 ± 14 N , recreational 248 ± 12 N , non-climbers 243 ± 11 N ) . For grip strength of the right h and , the elite climbers recorded significantly higher values than the recreational climbers only ( elite 338 ± 12 N , recreational 289 ± 10 N , non-climbers 307 ± 11 N ) . The results suggest that elite climbers have greater finger strength than recreational climbers and non-climbers PURPOSE Considering the development of rock climbing as a competitive sport , we aim ed at investigating the influence of four recovery methods on subsequent maximal climbing performance . METHODS In a r and omly assigned crossover design , 13 female well-trained climbers ( 27.1 + /- 8.9 yr ) came to the climbing center on four occasions separated by 1 wk . On each occasion , they had to perform two climbing tests ( C1 and C2 ) until volitional exhaustion on a pre practice d route ( overhanging wall , level 6b ) . These two tests were separated by 20 min of recovery . Four recovery methods were used in r and omized order : passive recovery , active recovery ( cycle ergometer , 30 - 40 W ) , electromyostimulation on the forearm muscles ( bisymmetric TENS current ) , or cold water immersion of the forearms and arms ( three periods of 5 min at 15 + /- 1 degrees C ) . Climbing tests ' performance was reflected by the number of arm movements and climb duration . RESULTS Using active recovery and cold water immersion , performance at C2 was maintained in comparison with C1 , whereas C2 performance was impaired compared with C1 ( P < 0.01 ) using electromyostimulation and passive recovery ( recovery method -by-climb interaction , P < 0.05 ) . Blood lactate decreased during recovery , with the greatest decrease occurring during active recovery ( time-by-recovery method interaction , P < 0.001 ) . Arms and forearms ' skin temperatures were lower throughout the cold water immersion compared with the other three methods ( P < 0.001 ) . CONCLUSION Active recovery and cold water immersion are two means of preserving performance when repeating acute exhausting climbing trails in female climbers . These positive effects are accompanied by a greater lactate removal and a decrease in subcutaneous tissues temperatures , respectively The aim of the present work was to characterize the modifications of the postural adjustments during a climbing task as a function of postural and /or movement constraints . The variations of the horizontal and vertical forces and momentum were analyzed for different movement amplitudes and types of holds . The results show that the horizontal momentum is influenced by all experimental conditions before the onset of movement . By contrast , the vertical momentum is only influenced by the amplitude of the movement , after its onset . These results confirm the hypothesis of a dual function of the anticipatory postural adjustments . The horizontal momentum is Output:	Results A low skinfold thickness , body fat and large forearm volume were anthropometric traits in successful climbers . Well-trained forearm flexors with high aerobic capacities lead to an efficient style . H and grip strength and endurance , postural stability and optimized kinematic motions were favourable . Elite climbers had long finger and bent-arm hang times . Psychologically , an " iceberg profile " was typical . Constant training with fingerboard and dynamic eccentric-concentric training helped to push the " red-point grade " . Conclusion H and , forearm strength and endurance are highly important elements in elite climbers . An efficient climbing style with perpetual focus and accuracy , high speed and low exhaustion due to adaption to repeated isometric exercise is helpful in the ascent , while low body fat and a large bone-to-tip pulp make it easier .
MS212091	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Allogeneic stem-cell transplantation ( HSCT ) is the only curative treatment in myelodysplastic syndromes ( MDS ) . Azacitidine ( AZA ) is increasingly used prior to HSCT , however in Europe it is only approved for patients who are not eligible for HSCT . Patients and methods We conducted a phase II multicenter study to prospect ively evaluate the feasibility of HSCT after treatment with AZA in 70 patients with a myelodysplastic syndrome ( MDS ) , 19 with acute myeloid leukemia ( AML ) , and 8 with chronic myelomonocytic leukemia ( CMML ) . After a median of four cycles ( range 1 - 11 ) : 24 % of patients achieved complete remission , 14 % partial remission , 8 % hematologic improvement , 32 % had stable and 22 % progressive disease . Ten patients discontinued treatment before the planned four cycles , due to an adverse event in nine cases . Results A HSC donor was identified in 73 patients , and HSCT was performed in 54 patients ( 74 % of patients with a donor ) . Main reasons for turning down HSCT were lack of a donor , an adverse event , or progressive disease ( 9 , 12 , and 16 patients , respectively ) . At a median follow-up of 20.5 months from enrolment , response to AZA was the only independent prognostic factor for survival . Compared to baseline assessment , AZA treatment did not affect patients ' comorbidities at HSCT : the HCT-CI remained stable in 62 % patients , and worsened or improved in 23 % and 15 % of patients , respectively . Conclusions Our study shows that HSCT is feasible in the majority of patients with HR-MDS/AML/CMML-2 after AZA treatment . As matched unrelated donor was the most frequent source of donor cells , the time between diagnosis and HSCT needed for donor search could be ' bridged ' using azacitidine . These data show that AZA prior to HSCT could be a better option than intensive chemotherapy in higher-risk MDS . The trial has been registered with the EudraCT number 2010 - 019673 - 1 Cytoreduction before allogeneic stem cell transplantation ( allo-SCT ) for patients with myelodysplastic syndromes remains a debatable issue . After excluding patients who had received preconditioning induction chemotherapy , we analyzed 128 consecutive patients with myelodysplastic syndrome who received reduced-intensity or nonmyeloablative conditioning ( RIC/NMA ) allo-SCT . Among them , 40 received azacitidine ( AZA ) before transplant ( AZA group ) and 88 were transplanted up front ( best supportive care [ BSC ] group ) . At diagnosis , 55 patients had intermediate 2 or high-risk scores per the International Prognostic Scoring System and 33 had a high cytogenetic risk score . Progression to a more advanced disease before allo-SCT was recorded in 22 patients . Source of stem cells were blood ( n = 112 ) or marrow ( n = 16 ) from sibling ( n = 78 ) or HLA-matched unrelated ( n = 50 ) donors . With a median follow-up of 60 months , 3-year overall survival , relapse-free survival , cumulative incidence of relapse , and nonrelapse mortality were , respectively , 53 % versus 53 % ( P = .69 ) , 37 % versus 42 % ( P = .78 ) , 35 % versus 36 % ( P = .99 ) , and 20 % versus 23 % ( P = .74 ) , for the AZA group and BSC group , respectively . Multivariate analysis confirmed the absence of statistical differences in outcome between the AZA and BSC groups , after adjusting for potential confounders using the propensity score approach . The absence of cytoreduction before RIC/NMA allo-SCT did not seem to alter the outcome . However , our results emphasize the need to perform prospect i ve protocol s to delineate the role of debulking strategy and to identify subsets of patients who may benefit from this approach This analysis compared azacitidine ( AZA ) to conventional care regimens ( CCR ) and their associated overall survival ( OS ) and tolerability in the subset of 87 elderly ( ≥ 75 years ) patients with higher-risk MDS ( FAB : RAEB , RAEB-t , CMML and IPSS : Int-2 or High ) from the AZA-001 trial . Patients were r and omized to AZA ( 75 mg/m(2)/daysubcutaneously × 7 days every 28 days ) ( n=38 ) or CCR ( n=49 ) and had median ages of 78 and 77 years , respectively . AZA significantly improved OS vs CCR ( HR : 0.48 [ 95%CI : 0.26 , 0.89 ] ; p=0.0193 ) and 2-year OS rates were 55 % vs 15 % ( p<0.001 ) , respectively . AZA was generally well tolerated compared with CCR , which was primarily best supportive care ( 67 % ) . Grade 3 - 4 anemia , neutropenia , and thrombocytopenia with AZA vs CCR were 13 % vs 4 % , 61 % vs 17 % , and 50 % vs 30 % , respectively . Given this efficacy and tolerability , AZA should be considered the treatment of choice in patients aged ≥ 75 years with good performance status and higher-risk MDS Aberrant DNA methylation , which results in leukemogenesis , is frequent in patients with myelodysplastic syndromes ( MDS ) and is a potential target for pharmacologic therapy . Decitabine indirectly depletes methylcytosine and causes hypomethylation of target gene promoters In a study of elderly AML patients treated with the hypomethylating agent decitabine ( DAC ) , we noted a surprisingly favorable outcome in the ( usually very unfavorable ) subgroup with two or more autosomal monosomies ( MK2 + ) within a complex karyotype ( Lübbert et al. , Haematologica 97:393 - 401 , 2012 ) . We now analyzed 206 myelodysplastic syndrome ( MDS ) patients ( 88 % of 233 patients r and omized in the EORTC/GMDSSG phase III trial 06011 , 61 of them with RAEBt , i.e. AML by WHO ) with cytogenetics informative for MK status .. Endpoints are the following : complete/partial ( CR/PR ) and overall response rate ( ORR ) and progression-free ( PFS ) and overall survival ( OS ) . Cytogenetic subgroups are the following : 63 cytogenetically normal ( CN ) patients , 143 with cytogenetic abnormalities , 73 of them MK-negative ( MK− ) , and 70 MK-positive ( MK+ ) . These MK+ patients could be divided into 17 with a single autosomal monosomy ( MK1 ) and 53 with at least two monosomies ( MK2 + ) . ORR with DAC in CN patients : 36.1 % , in MK− patients : 16.7 % , in MK+ patients : 43.6 % ( MK1 : 44.4 % , MK2 + 43.3 % ) . PFS was prolonged by DAC compared to best supportive care ( BSC ) in the CN ( hazard ratio ( HR ) 0.55 , 99 % confidence interval ( CI ) , 0.26 ; 1.15 , p = 0.03 ) and MK2 + ( HR 0.50 ; 99 % CI , 0.23 ; 1.06 , p = 0.016 ) but not in the MK− , MK+ , and MK1 subgroups . OS was not improved by DAC in any subgroup . In conclusion , we demonstrate for the first time in a r and omized phase III trial that high-risk MDS patients with complex karyotypes harboring two or more autosomal monosomies attain encouraging responses and have improved PFS with DAC treatment compared to BSC Background Few studies thus far have compared head-to-head different non-myelooablative conditioning regimens for allogeneic hematopoietic cell transplantation ( allo-HCT ) . Methods Here , we report the results of a phase II multicenter r and omized study comparing non-myeloablative allo-HCT from HLA-identical siblings ( n = 54 ) or from 10/10 HLA-matched unrelated donors ( n = 40 ) with either fludarabine plus 2 Gy total body irradiation ( Flu-TBI arm ; n = 49 ) or 8 Gy TLI + anti-thymocyte globulin ( TLI-ATG arm ; n = 45 ) conditioning . Results The 180-day cumulative incidences of grade II-IV acute GVHD ( primary endpoint ) were 12.2 % versus 8.9 % in Flu-TBI and TLI-ATG patients , respectively ( P = 0.5 ) . Two-year cumulative incidences of moderate/severe chronic GVHD were 40.8 % versus 17.8 % in Flu-TBI and TLI-ATG patients , respectively ( P = 0.017 ) . Five Flu-TBI patients and 10 TLI-ATG patients received pre-emptive DLI for low donor chimerism levels , while 1 Flu-TBI patient and 5 TLI-ATG patients ( including 2 patients given prior pre-emptive DLIs ) received a second HCT for poor graft function , graft rejection , or disease progression . Four-year cumulative incidences of relapse/progression were 22 % and 50 % in Flu-TBI and TLI-ATG patients , respectively ( P = 0.017 ) . Four-year cumulative incidences of nonrelapse mortality were 24 % and 13 % in Flu-TBI and TLI-ATG patients , respectively ( P = 0.5 ) . Finally , 4-year overall ( OS ) and progression-free survivals ( PFS ) were 53 % and 54 % , respectively , in the Flu-TBI arm , versus 54 % ( P = 0.9 ) and 37 % ( P = 0.12 ) , respectively , in the TLI-ATG arm . Conclusions In comparison to patients included in the Flu-TBI arm , patients included in the TLI-ATG arm had lower incidence of chronic GVHD , higher incidence of relapse and similar OS.Trial registration The study was registered on Clinical Trial.gov ( NCT00603954 ) and EUDRACT ( 2010 - 024297 - 19 ) Background The treatment of acute myeloid leukemia of older , medically non-fit patients still poses a highly unmet clinical need , and only few large , prospect i ve studies have been performed in this setting . Given the established activity of hypomethylating agents such as 5-aza-2'-deoxycytidine ( decitabine ) in myelodysplastic syndromes and acute myeloid leukemia with 20–30 % bone marrow blasts , we investigated whether this drug is also active in patients with more than 30 % blasts . Design and Methods To evaluate the efficacy and toxicity of decitabine in patients over 60 years old with untreated acute myeloid leukemia ineligible for induction chemotherapy , 227 patients ( median age , 72 years ) , many with comorbidities , adverse cytogenetics and /or preceding myelodysplastic syndrome were treated with this hypomethylating agent . During the initial decitabine treatment ( 135 mg/m2 total dose infused intravenously over 72 hours every 6 weeks ) , a median of two cycles was administered ( range , 1–4 ) . All-trans retinoic acid was administered to 100 patients during course 2 . Fifty-two patients who completed four cycles of treatment subsequently received a median of five maintenance courses ( range , 1–19 ) with a lower dose of decitabine ( 20 mg/m2 ) infused over 1 hour on 3 consecutive days every 4–6 weeks . Results The complete and partial remission rate was 26 % , 95 % CI ( 20 % , 32 % ) , and an antileukemic effect was noted in 26 % of patients . Response rates did not differ between patients with or without adverse cytogenetics ; patients with monosomal karyotypes also responded . The median overall survival from the start of decitabine treatment was 5.5 months ( range , 0–57.5 + ) and the 1-year survival rate was 28 % , 95%CI ( 22%,34 % ) . Toxicities were predominantly hematologic . Conclusions Decitabine is well tolerated by older , medically non-fit patients with acute myeloid leukemia ; myelosuppression is the major toxicity . The response rate and overall survival were not adversely influenced by poor-risk cytogenetics or myelodysplastic syndrome . Because of these encouraging results , r and omized studies evaluating single-agent decitabine versus conventional treatment are warranted . The study is registered with the German Clinical Trials Registry , number DRKS00000069 BACKGROUND The molecular determinants of clinical responses to decitabine therapy in patients with acute myeloid leukemia ( AML ) or myelodysplastic syndromes ( M Output:	No evidence showed that patients with MDS will benefit from using HMAs before HSCT in long-term survival ( OS and RFS ) compared to chemotherapy or best supportive therapy , though older patients were more likely to benefit from pre-transplantation HMAs treatment in terms of long-term survival .
MS212092	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Investigations using intermediate end points as cancer surrogates are quicker , smaller , and less expensive than studies that use malignancy as the end point . We present a strategy for determining whether a given biomarker is a valid intermediate end point between an exposure and incidence of cancer . C and i date intermediate end points may be selected from case series , ecologic studies , and animal experiments . Prospect i ve cohort and sometimes case-control studies may be used to quantify the intermediate end point-cancer association . The most appropriate measure of this association is the attributable proportion . The intermediate end point is a valid cancer surrogate if the attributable proportion is close to 1.0 , but not if it is close to 0 . Usually , the attributable proportion is close to neither 1.0 nor 0 ; in this case , valid surrogacy requires that the intermediate end point mediate an established exposure-cancer relation . This would in turn imply that the exposure effect would vanish if adjusted for the intermediate end point . We discuss the relative advantages of intervention and observational studies for the validation of intermediate end points . This validation strategy also may be applied to intermediate end points for adverse reproductive outcomes and chronic diseases other than cancer Output:	The use of biomarkers in phase I trials has increased over the period from 1991 to 2002 . To date , biomarker utilization has made a limited and primarily supportive contribution to dose selection , the primary end point of phase I studies .
MS212093	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Investigators have proposed " predict , resect , and discard " strategies for diminutive ( ≤ 5 mm ) or small ( 6 - 9 mm ) polyps to reduce screening colonoscopy costs . Advanced histological features such as villous histology , high- grade dysplasia , and /or cancer in these polyps could deter adoption of these strategies . OBJECTIVE Determine the prevalence of advanced histological features in diminutive and small colon polyps . DESIGN Retrospective analysis of data from 3 prospect i ve clinical trials . SETTING Two tertiary-care referral centers . PATIENTS This study involved patients undergoing screening or surveillance colonoscopy . INTERVENTION The location , size , and morphology of each polyp detected was documented . Each polyp was then resected , placed in a unique specimen jar , and sent for histopathological evaluation . MAIN OUTCOME MEASUREMENTS Rates of advanced histological features ( villous histology , high- grade dysplasia , and cancer ) . RESULTS A total of 2361 polyps were detected , removed , and retrieved . Both diminutive and small polyps had a lower frequency of any advanced histological features compared with large polyps ( 0.5 % and 1.5 % , respectively vs 15.0 % ; P < .001 for both comparisons ) . Polyps < 10 mm in size had a lower frequency of advanced histology compared with polyps ≥ 10 mm ( 0.8 % vs 15.0 % ; P < .001 ) . During sensitivity analysis , the frequency of advanced histological features varied from 0.2 % to 0.7 % within diminutive polyps , 1.5 % to 3.6 % within small polyps , and 0.8 % to 1.2 % within polyps < 10 mm . LIMITATIONS Retrospective analysis from tertiary-care referral centers ; predominantly white , male , veteran patient population result ing in limited generalizability of results . CONCLUSION The prevalence of advanced histological features in colon polyps ≤ 5 mm is very low ( 0.5 % ) . This has important implication s for the potential practice of " predicting , resecting , and discarding " diminutive colon polyps Objective : Colonoscopy is the accepted gold st and ard for screening of neoplastic colorectal lesions , but the substantial miss rate remains a challenge . Computed virtual chromoendoscopy with the Fujinon intelligent colour enhancement ( FICE ) system is a new dyeless imaging technique that might allow higher rates of adenoma detection . Methods : This is a prospect i ve r and omised five tertiary care centre trial of colonoscopy in the FICE mode versus st and ard colonoscopy with targeted indigocarmine chromoscopy ( control group ) in consecutive patients attending for routine colonoscopy . Histopathology of detected lesions was confirmed by evaluation of endoscopic resection or biopsy specimens . Results : 871 patients were enrolled , and 764 patients ( 344 female , mean age 64 years ) were subjected to final analysis ( 368 in the FICE group , 396 in the control group ) . In total , 236 adenomas ( mean of 0.64 per case ) were detected in the FICE group and 271 adenomas ( mean of 0.68 per case ) in the control group ( p = 0.92 ) . There was no statistically significant difference in the percentage of patients with ⩾1 adenoma between the control group ( 35.4 % ) and the FICE group ( 35.6 % ) ( p = 1.0 ) . For the differential diagnosis of adenomas and non-neoplastic polyps , the sensitivity of FICE ( 92.7 % ) was comparable with that of indigocarmine ( 90.4 % ) ( p = 0.44 ) . Conclusions : At colonoscopy , adenoma detection rates are not improved by virtual chromoendoscopy with the FICE system compared with white light endoscopy with targeted indigocarmine spraying . However , FICE can effectively substitute for chromoscopy concerning the differentiation of neoplastic and non-neoplastic lesions BACKGROUND Probe-based confocal laser endomicroscopy ( pCLE ) is an emerging tool for in vivo imaging of the GI tract that requires the endoscopist to interpret microscopic images . The learning curve for interpretation of pCLE images is unknown . OBJECTIVE To examine the learning curve of correctly identifying benign and neoplastic colorectal lesions by using pCLE and to evaluate the learning curve of obtaining high- quality images . DESIGN Prospect i ve , double-blind review of pCLE images of 76 colorectal lesions by using corresponding polypectomies as the reference st and ard . A training set of 20 images with known histology was first review ed to st and ardize image interpretation , followed by blinded review of 76 unknown images . SETTING Eleven endoscopists from 3 different endoscopy centers evaluated the images obtained by 1 endoscopist using the high-definition confocal probe . PATIENTS Patients undergoing screening and surveillance colonoscopies . INTERVENTION Intravenous fluorescein pCLE imaging of colorectal lesions followed by polypectomies . MAIN OUTCOME MEASUREMENTS Accuracy of image interpretation with constructing learning curve for pCLE image interpretation and acquisition . RESULTS Of the 76 colorectal lesions , 51 ( 67 % ) were neoplastic and 25 ( 33 % ) were benign , based on histopathology . Accuracy for the overall group was 63 % for lesions 1 to 20 , 64 % for lesions 21 to 40 , 79 % for lesions 41 to 60 , and 86 % for lesions 61 to 76 . The ability to obtain high- quality images was stable over the 76 cases . LIMITATIONS Small sample size and use of offline video sequences . CONCLUSIONS Accurate interpretation of pCLE images for predicting neoplastic lesions can be learned rapidly by a wide range of GI specialists . Furthermore , the ability to acquire high- quality pCLE images is also quickly learned BACKGROUND The EPKi system ( Pentax , Japan ) enables resolution above HDTV . Aim of the study was to test the efficacy of HD+ alone and with the new post-processing digital filter i-Scan or chromoendoscopy ( Methylene blue 0.1 % ) in screening for colorectal cancer . We focused on lesions less than 5 mm as a surrogate marker for the optical possibilities of the EPKi system . METHODS The last 30 cm of the colon in a screening population were inspected with HD+ alone , in combination with i-Scan ( 2:1 r and omisation ) and subsequently with chromoendoscopy . All lesions were characterized and targeted biopsies were performed . RESULTS i-Scan augmented in 69 patients the identification of lesions from 176 to 335 ( p<0.001 ) and chromoendoscopy to 646 ( p<0.001 ) . The additional lesions were mainly flat ( type IIb , 74 % ) , which were only recognized using i-Scan or chromoendoscopy . The amount of neoplasias was not significantly different ( HD+ : 5 , i-Scan : 11 , Chromoendoscopy : 11 ) , but all could correctly be predicted using i-Scan or chromoendoscopy . CONCLUSIONS HD+ colonoscopy with and without i-Scan unmask a plethora of small lesions but chromoendoscopy can even advance the number . However , i-Scan was able to predict neoplasia as precisely as chromoendoscopy and might shortly replace chromoendoscopy as a more time efficient tool BACKGROUND AND STUDY AIMS Narrow-b and imaging ( NBI ) has shown promising results in discriminating adenomatous from non-adenomatous colonic polyps . In patients with small polyps ( < 10 mm ) , the application of NBI within a " resect and discard " strategy , might allow post-polypectomy surveillance intervals to be determined independently from histopathology . The aim of the present study was to assess the feasibility and safety of this approach in routine clinical practice . PATIENTS AND METHODS Consecutive colonoscopy out patients with one or more polyps smaller than 10 mm were prospect ively included . Each polyp was categorized by the endoscopist as adenoma or non-adenoma according to simplified NBI criteria , and future post-polypectomy surveillance interval was assigned accordingly . Following histopathology , post-polypectomy surveillance interval was subsequently re-assigned , and the accordance between endoscopy- and histology-directed surveillance strategies was calculated . RESULTS Among 942 colonoscopy patients , 286 ( 30.4 % ) with only small polyps were included . In total , 511 small polyps were evaluated ; 350 ( 68.5 % ) were adenomas and 18 of these ( 5.1 % ) had histologic features of advanced neoplasia . For the in vivo diagnosis of adenoma , NBI sensitivity , specificity , accuracy , and positive and negative likelihood ratios were 94.9 % , 65.8 % , 85.7 % , 2.80 , and 0.08 , respectively . The endoscopy-directed surveillance strategy was in accordance with the histology-directed strategy in 237 of 286 patients ( 82.9 % ) . In 9.8 % and 7.3 % patients , the endoscopy-directed approach would have result ed in early and delayed surveillance , respectively . CONCLUSIONS The resect and discard strategy seems to be a viable , safe , and cost-effective approach for the management of patients with small polyps . However , caution in the application of the strategy should be advocated for patients with polyps 6 - 9 mm in size and those with right-sided lesions , due to their malignant potential . The study was registered on Clinical trials.gov ( NCT01462123 ) Background and study aims Magnifying colonoscopy with indigo carmine dye and the analysis of the capillary and the pit patterns by computed virtual chromoendoscopy ( Fujinon Intelligent Color Enhancement , FICE ) with magnification are effective for the differential diagnosis of neoplastic and non-neoplastic lesions . This study aim ed to compare the accuracy of virtual and real chromoendoscopy in differentiating neoplastic and non-neoplastic colorectal lesions . Patients and methods A prospect i ve r and omized trial of magnification colonoscopy with targeted FICE ( Group I – 72 patients /111 lesions ) versus magnification colonoscopy with targeted indigo carmine dye ( Group II – 72 patients /137 lesions ) was performed in consecutive patients with lesions 1 cm or less . Histopathology of the specimens was regarded as the gold st and ard . Results In group I , 86 ( 77.5 % ) lesions showed an intense vascular pattern ( positive capillary meshwork ) , of which 80 ( 93 % ) were histologically confirmed as adenomas . From 25 lesions with negative capillary meshwork , 23 ( 92 % ) were non-neoplastic . Sensitivity , specificity , accuracy , positive and negative predictive values of the capillary meshwork for the differential diagnosis of these lesions was 97.8 , 79.3 , 92.8 , 93 and 92 % , respectively . The same parameters for pit pattern analysis by FICE were 92.7 , 82.3 , 90.1 , 93.8 and 80 % , respectively . Indigo carmine magnified chromoscopy showed sensitivity , specificity , accuracy , positive and negative predictive values of 97 , 88.9 , 94.9 , 96.1 and 91.4 % , respectively in the discrimination between neoplastic and non-neoplastic lesions . Conclusion Magnified virtual chromoendoscopy is as accurate as indigo carmine magnified chromoendoscopy in distinguishing between neoplastic from non-neoplastic small colorectal lesions BACKGROUND Digital chromoendoscopy ( DCE ) has the potential for the in vivo optical diagnosis of colon polyps . However , no comparison of different DCE technologies currently exists . OBJECTIVE To compare the diagnostic efficacies of narrow-b and imaging ( NBI ) with those of I-Scan for the real-time histological prediction of diminutive colonic polyps ( DCPs ) ( ≤5 mm ) by using the simple unified endoscopic classification . DESIGN Prospect i ve cohort study . SETTING Academic hospital . PATIENTS In total , 296 DCPs from 142 patients undergoing screening or surveillance colonoscopy were assessed . INTERVENTIONS All DCPs detected during withdrawal were evaluated for the surface details by using high-definition white-light colonoscopy , and thereafter by using DCE ( NBI or I-Scan ) without optical magnification . The histology of all polyps was predicted in real-time and confirmed through the evaluation of biopsy or polypectomy specimens . MAIN OUTCOME MEASUREMENTS Diagnostic efficacies of NBI and I-Scan . RESULTS NBI and I-Scan displayed a significantly higher sensitivity and improved accuracy compared with high-definition white-light colonoscopy for the prediction of adenomas ( P < .05 ) . No significant differences were evident between the NBI and I-Scan ( sensitivity , 88.8 % vs 94.6 % ; specificity , 86.8 % vs 86.4 % ; accuracy , 87.8 % vs 90.7 % , respectively ; P > .05 ) . Additionally , substantial levels of intra- and interobserver agreement between the NBI and I-Scan were measured ( κ values > 0.7 ) . LIMITATIONS No r and omized or Output:	Our meta-analyses indicate that optical biopsy with NBI , exceeds the NPV threshold for adenomatous polyp histology , supporting a " diagnose- and -leave " strategy for diminutive predicted nonneoplastic polyps in the rectosigmoid colon .
MS212094	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE Infobuttons are message-based content search and retrieval functions embedded within other applications that dynamically return information relevant to the clinical task at h and . The objective of this study was to determine whether infobuttons effectively answer providers ' questions about medications or affect patient care decisions . DESIGN The authors implemented and evaluated a medication infobutton application called KnowledgeLink . Health care providers at 18 outpatient clinics were r and omized to one of two versions of KnowledgeLink , one that linked to information from Micromedex ( Thomson Micromedex , Greenwood Village , Co ) and the other to material from SkolarMD ( Wolters Kluwer Health , Palo Alto , CA ) . MEASUREMENTS Data were collected about the frequency of use and demographics of users , patients , and drugs that were queried . Users were periodically surveyed with short question naires and then with a more extensive survey at the end of one year . RESULTS During the first year , KnowledgeLink was used 7,972 times by 359 users to look up information about 1,723 medications for 4,961 patients . Clinicians used KnowledgeLink twice a month on average , and during an average of 1.2 % of patient encounters . KnowledgeLink was used by a wide variety of medical staff , not just physicians and nurse practitioners . The frequency of usage and the questions asked varied with user role ( primary care physician , specialist physician , nurse practitioner ) . Although the median KnowledgeLink session was brief ( 21 seconds ) , KnowledgeLink answered users ' queries 84 % of the time , and altered patient care decisions 15 % of the time . Users rated KnowledgeLink favorably on multiple scales , recommended extending KnowledgeLink to other content domains , and suggested enhancing the interface to allow refinement of the query and selection of the target re source . CONCLUSION An infobutton can satisfy information needs about medications . Although used infrequently and for brief sessions , KnowledgeLink was positively received , answered most users ' questions , and had a significant impact on medical decision making . The next steps would be to broaden the domains that KnowledgeLink covers to more specifically tailor results to the user type , to provide options when queries are not immediately answered , and to implement KnowledgeLink within other electronic clinical applications OBJECTIVE Authors evaluated whether displaying context sensitive links to infrequently accessed educational material s and patient information via the user interface of an inpatient computerized care provider order entry ( CPOE ) system would affect access rates to the material s. DESIGN The CPOE of V and erbilt University Hospital ( VUH ) included " baseline " clinical decision support advice for safety and quality . Authors augmented this with seven new primarily educational decision support features . A prospect i ve , r and omized , controlled trial compared clinicians ' utilization rates for the new material s via two interfaces . Control subjects could access study -related decision support from a menu in the st and ard CPOE interface . Intervention subjects received active notification when study -related decision support was available through context sensitive , visibly highlighted , selectable hyperlinks . MEASUREMENTS Rates of opportunities to access and utilization of study -related decision support material s from April 1999 through March 2000 on seven VUH Internal Medicine wards . RESULTS During 4,466 intervention subject-days , there were 240,504 ( 53.9/subject-day ) opportunities for study -related decision support , while during 3,397 control subject-days , there were 178,235 ( 52.5/subject-day ) opportunities for such decision support , respectively ( p = 0.11 ) . Individual intervention subjects accessed the decision support features at least once on 3.8 % of subject-days logged on ( 278 responses ) ; controls accessed it at least once on 0.6 % of subject-days ( 18 responses ) , with a response rate ratio adjusted for decision support frequency of 9.17 ( 95 % confidence interval 4.6 - 18 , p < 0.0005 ) . On average , intervention subjects accessed study -related decision support material s once every 16 days individually and once every 1.26 days in aggregate . CONCLUSION Highlighting availability of context -sensitive educational material s and patient information through visible hyperlinks significantly increased utilization rates for study -related decision support when compared to " st and ard " VUH CPOE methods , although absolute response rates were low Abstract Objectives : To characterise the information needs of family doctors by collecting the questions they asked about patient care during consultations and to classify these in ways that would be useful to developers of knowledge bases . Design : Observational study in which investigators visited doctors for two half days and collected their questions . Taxonomies were developed to characterise the clinical topic and generic type of information sought for each question . Setting : Eastern Iowa . Participants : R and om sample of 103 family doctors . Main outcome measures : Number of questions posed , pursued , and answered ; topic and generic type of information sought for each question ; time spent pursuing answers ; information re sources used . Results : Participants asked a total of 1101 questions . Questions about drug prescribing , obstetrics and gynaecology , and adult infectious disease were most common and comprised 36 % of all questions . The taxonomy of generic questions included 69 categories ; the three most common types , comprising 24 % of all questions , were “ What is the cause of symptom X ? ” “ What is the dose of drug X ? ” and “ How should I manage disease or finding X ? ” Answers to most questions ( 702 , 64 % ) were not immediately pursued , but , of those pursued , most ( 318 , 80 % ) were answered Doctors spent an average of less than 2 minutes pursuing an answer , and they used readily available print and human re sources Only two questions led to a formal literature search . Conclusions : Family doctors in this study did not pursue answers to most of their questions . Questions about patient care can be organised into a limited number of generic types , which could help guide the efforts of knowledge base developers . Key messages Questions that doctors have about the care of their patients could help guide the content of medical information sources and medical training In this study of US family doctors , participants frequently had questions about patient care but did not pursue answers to most questions ( 64 % ) On average , participants spent less than 2 minutes seeking an answer to a question The most common re sources used to answer questions included textbooks and colleagues ; formal literature search es were rarely performed The most common generic questions were “ What is the cause of symptom X ? ” “ What is the dose of drug X ? ” and “ How should I manage disease or finding X ? OBJECTIVE Infobuttons are decision support tools that provide links within electronic medical record systems to relevant content in online information re sources . The aim of infobuttons is to help clinicians promptly meet their information needs . The objective of this study was to determine whether infobutton links that direct to specific content topics ( " topic links " ) are more effective than links that point to general overview content ( " nonspecific links " ) . DESIGN R and omized controlled trial with a control and an intervention group . Clinicians in the control group had access to nonspecific links , while those in the intervention group had access to topic links . MEASUREMENTS Infobutton session duration , number of infobutton sessions , session success rate , and the self-reported impact that the infobutton session produced on decision making . RESULTS The analysis was performed on 90 subjects and 3,729 infobutton sessions . Subjects in the intervention group spent 17.4 % less time seeking for information ( 35.5 seconds vs. 43 seconds , p = 0.008 ) than those in the control group . Subjects in the intervention group used infobuttons 20.5 % ( 22 sessions vs. 17.5 sessions , p = 0.21 ) more often than in the control group , but the difference was not significant . The information seeking success rate was equally high in both groups ( 89.4 % control vs. 87.2 % intervention , p = 0.99 ) . Subjects reported a high positive clinical impact ( i.e. , decision enhancement or knowledge up date ) in 62 % of the sessions . Limitations The exclusion of users with a low frequency of infobutton use and the focus on medication-related information needs may limit the generalization of the results . The session outcomes measurement was based on clinicians ' self- assessment and therefore prone to bias . CONCLUSION The results support the hypothesis that topic links are more efficient than nonspecific links regarding the time seeking for information . It is unclear whether the statistical difference demonstrated will result in a clinical ly significant impact . However , the overall results confirm previous evidence that infobuttons are effective at helping clinicians to answer questions at the point of care and demonstrate a modest incremental change in the efficiency of information delivery for routine users of this tool Output:	Conclusions : Weak evidence suggests that infobuttons can help providers answer clinical questions .
MS212095	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: 60 patients , aged 15 - 51 years , with chronic allergic or bacterial maxillary sinusitis , were entered in a controlled , double-blind study comparing the efficacy of endonasal irrigations of tixocortol pivalate (Pivalone)-neomycin and neomycin . The treatment lasted 11 days and was administered once daily . A ventilometric measurement of sinus pressure was performed every two endonasal irrigations to assess treatment efficacy . The percentage of nasal deobstruction was significantly higher with tixocortol pivalate-neomycin than with neomycin alone by the fifth examination ( 9th day ) regardless of the etiology of the sinusitis ( allergic or bacterial ) . After 11 days of treatment , significantly better results were obtained in cases of bacterial sinusitis ( 94 % deobstruction with tixocortol pivalate-neomycin versus 74 % with neomycin ) than in cases of allergic sinusitis ( 69 % deobstruction with tixocortol pivalate-neomycin versus 36 % with neomycin ) BACKGROUND Chronic sinusitis ( CS ) is a common disease in children , especially those with allergies , that is caused by impaired drainage from the sinuses . Hypertonic NaCl solution has been shown to increase mucociliary clearance and ciliary beat frequency . OBJECTIVE We performed a r and omized double blind study to compare the effect of nasal wash with hypertonic saline ( HS ) ( 3.5 % ) versus normal saline ( NS ) ( 0.9 % ) on CS . METHODS Thirty patients with CS aged 3 to 16 years were studied . They were r and omly divided into two treatment groups matched by age and severity of the disease . Each individual was treated with either HS or NS for 4 weeks . All patients were evaluated by two clinical scores ( cough and nasal secretions/postnasal drip [ PND ] ) and by a radiology score at the beginning of the study and after 4 weeks . RESULTS The HS group improved significantly in all scores ( average + /- SD ) : cough score , from 3.6 + /- 0.51 to 1.6 + /- 0.74 ; nasal secretion/PND score , from 2.86 + /- 0.35 to 1.6 + /- 0.74 ; and radiology score , from 8.06 + /- 1.28 to 2.66 + /- 1.04 . The NS treatment group showed significant improvement only in the PND score ( from 2.66 + /- 0.49 to 1.53 + /- 0.83 ) but no significant change in both the cough score ( from 3.53 + /- 0.52 to 3.33 + /- 0.49 ) and the radiology score ( from 8.13 + /- 1.25 to 7.86 + /- 0.91 ) . Clinical observation 1 month after the end of the study showed no change compared with the end of the study in both groups . CONCLUSION HS nasal wash is an efficient treatment of CS OBJECTIVES To test whether daily hypertonic saline nasal irrigation improves sinus symptoms and quality of life and decreases medication use in adult subjects with a history of sinusitis . STUDY DESIGN R and omized controlled trial . Experimental subjects used nasal irrigation daily for 6 months . POPULATION Seventy-six subjects from primary care ( n=70 ) and otolaryngology ( n=6 ) clinics with histories of frequent sinusitis were r and omized to experimental ( n=52 ) and control ( n=24 ) groups . OUTCOMES MEASURED Primary outcome measures included the Medical Outcomes Survey Short Form ( SF-12 ) , the Rhinosinusitis Disability Index ( RSDI ) , and a Single-Item Sinus-Symptom Severity Assessment ( SIA ) ; all 3 were completed at baseline , 1.5 , 3 , and 6 months . Secondary outcomes included daily assessment of compliance and biweekly assessment of symptoms and medication use . At 6 months , subjects reported on side effects , satisfaction with nasal irrigation , and the percentage of change in their sinus-related quality of life . RESULTS No significant baseline differences existed between the 2 groups . Sixty-nine subjects ( 90.8 % ) completed the study . Compliance averaged 87 % . Experimental group RSDI scores improved from 58.4 -/+ 2.0 to 72.8 -/+ 2.2 ( P < or = .05 ) compared with those of the control group ( from 59.6 -/+ 3.0 to 60.4 -/+ 1.1 ) ; experimental group SIA scores improved from 3.9 -/+ 0.1 to 2.4 -/+ 0.1 ( P < or = .05 ) compared with those of the control group ( from 4.08 -/+ 0.15 to 4.07 -/+ 0.27 ) . The number needed to treat to achieve 10 % improvement on RSDI at 6 months was 2.0 . Experimental subjects reported fewer 2-week periods with sinus-related symptoms ( P < .05 ) , used less antibiotics ( P < .05 ) , and used less nasal spray ( P = .06 ) . On the exit question naire 93 % of experimental subjects reported overall improvement of sinus-related quality of life , and none reported worsening ( P < .001 ) ; on average , experimental subjects reported 57 -/+ 4.5 % improvement . Side effects were minor and infrequent . Satisfaction was high . We found no statistically significant improvement on the SF-12 . CONCLUSIONS Daily hypertonic saline nasal irrigation improves sinus-related quality of life , decreases symptoms , and decreases medication use in patients with frequent sinusitis . Primary care physicians can feel comfortable recommending this therapy BACKGROUND Nasal irrigation has been used as an adjunctive therapy of sinonasal disease including acute/chronic sinusitis and allergic rhinitis . Several published articles reported it also improves clinical sinus symptoms . OBJECTIVE To evaluate the effectiveness of normal saline nasal irrigation in the management of acute sinusitis in children . DESIGN This was a r and omized , prospect i ve placebo-controlled study . METHODS We included 69 participants with acute sinusitis . 30 of 69 participants underwent normal saline nasal irrigation . 39 of 69 participants were not receiving nasal irrigation . All participants performed nasal peak expiratory flow rate ( nPEFR ) test , nasal smear examination , radiography ( Water 's projection ) and requested to complete the Pediatric Rhinoconjunctivitis Quality of Life Question naires ( PRQLQ ) at the baseline visit . All participants were requested to record the symptom diary card every day and were followed-up every 1 week during this period . A physical examination , nasal smear and nPEFR were performed at each visit , and all daily diary cards collected . At the final visit , the symptoms diaries were review ed and participants were requested to complete the PRQLQ again . The nPEFR , radiography ( Water 's projection ) and nasal smear were also repeated . RESULTS Normal saline irrigation group significantly improved mean PRQLQ values and nPEFR values at medium ( T=2.816 , P<0.05 ) and final period ( T=2.767 , P<0.05 ) compared with the other group . Although there were no statically significant improving rate of radiography ( Water 's projection ) in among two groups ( T=0.545 , P>0.05 ) , but normal saline irrigation group was better than the other group . The improval rate of mean TSS in the irrigation group significantly improved all symptoms compared with the placebo group , in which rhinorrhea , nasal congestion , throat itching , cough and sleep quality improved . 27 of 66 ( 40.9 % ) participants with atopy , 16 of 27 ( 53.33 % ) participants underwent normal saline irrigation . Normal saline irrigation atopy group significantly improved rhinorrhea , nasal congestion , throat itching and sleep quality symptoms compared with non-irrigation atopy group . Normal saline irrigation atopy group significantly improved nPEFR values at final period ( Z=2.53 , P<0.05 ) . CONCLUSION This study evidence that normal saline nasal irrigation improves Pediatric Rhinoconjunctivitis Quality of Life and decreases acute sinusitis symptoms . Nasal irrigation is an effective adjunctive treatment for pediatric acute sinusitis . Normal saline nasal irrigation in atopy children also improves allergic-related symptoms . We may need larger , longer and extended study to assess the conclusion Antibiotic abuse for treating rhinopharyngitis induces the occurrence of resistant bacteria . As topical drugs might reduce this phenomenon , the aims of our study are to evaluate inhaled thiamphenicol associated with acetylcysteine in children with acute bacterial rhinopharyngitis and to compare it with the use of saline solution . The trial was conducted as r and omized , parallel group , and single blind . Children , aged 3–6 years , with acute bacterial rhinopharyngitis were treated with aerosolized thiamphenicol associated with acetylcysteine ( 250 mg : ½ vial in the morning and ½ vial in the evening ) ( Group A ) or saline solution twice daily ( Group B ) , both of them for 5 days . Both treatments were administered using a new device : Rinowash . The following parameters were assessed : nasal obstruction , mucopurulent rhinorrhea , post-nasal drip , cough , sore throat , fever , and cultures . Of 104 patients screened , 90 children , median age 3.7 years ( 44 females and 46 males ) , completed the study : 60 in Group A and 30 in Group B. Actively-treated children achieved a significant improvement of all parameters , but fewer than the control group . In conclusion , inhaled thiamphenicol associated with acetylcysteine may represent a valid treatment for acute bacterial rhinopharyngitis in children , as it is effective , safe , economic , and simple to use BACKGROUND The role of topical corticosteroids in the treatment of acute sinusitis has not been established in children . OBJECTIVE An attempt was made to determine the impact of topical corticosteroids as an adjunct to antibiotic treatment in the management of childhood sinusitis . METHODS In a double-blind , placebo-controlled study , 151 children with sinusitis were recruited from a general pediatric outpatient clinic and 89 completed a 3-week trial . Treatment consisted of amoxicillin-clavulanate potassium , 40 mg/kg/d tid , combined with bid nasal spray of either budesonide , 50 micrograms , to each nostril ( n = 43 ) or placebo ) n = 46 _ for 3 weeks . Patients maintained daily symptom cards throughout the study and were examined by the same physician each week . RESULTS Clinical symptoms and signs decreased significantly in both treatment groups in comparison to baseline ( P < .01 ) . We detected a significant improvement in the scores of the cough and nasal discharge at the end of second week in the budesonide group when compared with placebo ( P < .05 ) . Friedman nonparametric repeated measures ANOVA test revealed a significant decrease in the total weekly scores of cough during the second week of budesonide treatment ( P < .001 ) in contrast to continuous decline during the second and third weeks in the placebo group ( P < .001 and P < .05 , respectively ) . While the nasal discharge score decreased significantly during the second week in the budesonide group ( P < .01 ) , no significant effect on the nasal discharge score was observed in the placebo group . CONCLUSION These data suggest that topical corticosteroids may be a useful ancillary treatment to antibiotics in childhood sinusitis and effective in reducing the cough and nasal discharge earlier in the course of acute sinusitis OBJECTIVE The objective of this r and omized , prospect i ve , double-blind study was to compare nasal irrigation using hypertonic Dead Sea salt ( DSS ) solution with hypertonic saline in the treatment of chronic rhinosinusitis and improvement of quality of life ( QOL ) . METHODS With Institutional Review Board approval , 42 adults seeking treatment for chronic rhinosinusitis in a tertiary university-affiliated medical center were studied . After history and endonasal examination , computed tomography imaging , and QOL survey ( St and ardized Rhinoconjunctivitis Quality of Life Question naire [ RQLQ(S ) ] ) , patients were r and omized to self-administered hypertonic saline spray and irrigation twice daily or hypertonic DSS spray and irrigation . Patients were reassessed weekly and at 1 month . RESULTS Both groups had similar symptoms and RQLQ(S ) scores before treatment and had significant improvement after treatment . However , the DSS patients had significantly better symptom relief and only the DSS group showed improved RQLQ(S ) scores . CONCLUSIONS We present a short-term study providing level I evidence on the superiority of DSS over saline nasal irrigation for treatment of chronic rhinosinusitis preparation , and phenylephrine plus nitrofurazone 0.02 per cent solution t as the test preparation . Each was dispensed in a plastic dropping container marked only with a code number ; neither patient nor physician knew to which group the patient had been assigned . All 100 patients ---541 in each group-were from a general practice in pediatrics and had purulent rhinitis . Each patient was provided Purulent nasal discharge Output:	There is no evidence to determine whether the use of antihistamines , decongestants or nasal irrigation is efficacious in children with acute sinusitis .
MS212096	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The catechol-O-methyltranferase ( COMT ) is one of the main enzymes that metabolise dopamine in the brain . The Val158Met polymorphism in the COMT gene ( rs4680 ) causes a trimodal distribution of high ( Val/Val ) , intermediate ( Val/Met ) and low ( Met/Met ) enzyme activity . We tested whether the Val158Met polymorphism is a modifier of the age at onset ( AAO ) in Parkinson 's disease ( PD ) . The rs4680 was genotyped in a total of 16 609 subjects from five independent cohorts of European and North American origin ( 5886 patients with PD and 10 723 healthy controls ) . The multivariate analysis for comparing PD and control groups was based on a stepwise logistic regression , with gender , age and cohort origin included in the initial model . The multivariate analysis of the AAO was a mixed linear model , with COMT genotype and gender considered as fixed effects and cohort and cohort-gender interaction as r and om effects . COMT genotype was coded as a quantitative variable , assuming a codominant genetic effect . The distribution of the COMT polymorphism was not significantly different in patients and controls ( p=0.22 ) . The Val allele had a significant effect on the AAO with a younger AAO in patients with the Val/Val ( 57.1±13.9 , p=0.03 ) than the Val/Met ( 57.4±13.9 ) and the Met/Met genotypes ( 58.3±13.5 ) . The difference was greater in men ( 1.9 years between Val/Val and Met/Met , p=0.007 ) than in women ( 0.2 years , p=0.81 ) . Thus , the Val158Met COMT polymorphism is not associated with PD in the Caucasian population but acts as a modifier of the AAO in PD with a sexual dimorphism : the Val allele is associated with a younger AAO in men with idiopathic PD Patients with Parkinson 's Disease ( PD ) have a variable response to tolcapone , a catechol-O-methyltransferase ( COMT ) inhibitor . In addition , a subset of patients develop severe diarrhea as a side effect . Two codominant alleles for the COMT gene exist , coding for low and high activity , result ing in low- , medium- , and high-activity genotypes . This study investigates the relationship between this variation in genotype and clinical effects in patients with PD taking tolcapone . To investigate the relationship between COMT polymorphism and clinical response , 24 patients who completed tolcapone clinical trials provided blood sample s for COMT genotype analysis . Change in levodopa dose and United Parkinson Disease Rating Scale ( UPDRS ) Part III ( motor subscale ) were analyzed at baseline , at 1–2 weeks , and 6 months after initiation of tolcapone . Genotype analysis was performed on seven patients who had diarrhea as a side effect . There was no significant correlation between genotype and improvement in UPDRS score ( p = 0.29 ) according to a linear models approach that adjusted for the subject 's severity of PD , tolcapone dose ( either 100 or 200 mg three times daily ) and initial differences in baseline scores . No significant difference was seen in change in daily levodopa intake and genotype . There was also no relation between diarrhea and COMT genotype . These results indicate that , in the treatment of Parkinson 's disease , COMT genotype is not a major contributor to the clinical response to tolcapone Background A polymorphism ( G to A transition ) in intron 13 of the mitochondrial enzyme monoamine oxidase B ( MAOB ) gene may modify , alone or by interacting with the catechol-O-methyltransferase ( COMTLL ) genotype ( low enzymatic activity ) , the risk of idiopathic PD . Also , the association between never smoking and PD risk may be present only in people with the MAOB G allele . Methods The authors studied two ongoing prospect i ve cohorts — the Nurses ’ Health Study ( 121,700 women aged 30 to 55 in 1976 ) and the Health Professionals ’ Follow-up Study ( 51,529 men aged 40 to 75 in 1986 ) . They identified new PD cases through 1996 , selected r and om control subjects matched on age and study cohort , and obtained DNA sample s from blood or buccal smears from 85 % of the eligible cases and 84 % of the control subjects . They included genotypes from 214 cases and 449 control subjects , all Caucasian . Results The odds ratio of PD was 1.2 ( 95 % CI 0.9 , 1.7 ) for MAOB genotypes G/GG/GA compared with genotypes A/AA , and 1.1 ( 0.7 , 1.8 ) for COMT genotypes LL compared with HH . The odds ratio ( 95 % CI ) was 1.7 ( 0.7 , 3.9 ) for those with MAOB G/GG and COMTLL genotypes compared with those with MAOB A/AA and COMTHH . There was a strong association between never smoking and PD risk in all groups defined by MAOB and COMT genotypes . Conclusion The findings do not support a major role of the MAOB intron 13 polymorphism in the development of PD , either by itself or by interacting with smoking A single nucleotide polymorphism at the nucleotide 1947 in the catechol-O-methyltransferase ( COMT ) gene encodes the high and low activity forms of the enzyme . We investigated COMT genotypes of 73 Korean patients with Parkinson 's disease ( PD ) , 29 with multiple system atrophy ( MSA ) , and 49 controls , and analyzed the response to levodopa challenge in the PD patients . We found no significant difference in the distribution of the COMT genotypes among the three groups . The frequencies of the G- and A-alleles in the total population were 75 and 25 % , respectively . The levodopa response was determined by a single oral levodopa challenge test with Sinemet ( 25/250 mg ) in the patients with PD . The motor response evaluated by the time to peak response , the duration and magnitude of the response in the motor part of the Unified Parkinson 's Disease Rating Scale ; tapping or walking times showed no significant difference between the genotypes . Thus , pharmacokinetic or pharmacodynamic factors other than the investigated genetic variant of the COMT enzyme seem to determine the response to levodopa in PD The role of genetic factors in cognitive decline associated with Parkinson 's disease ( PD ) is unclear . We examined whether variations in apolipoprotein E ( APOE ) , microtubule-associated protein tau ( MAPT ) , or catechol-O-methytransferase ( COMT ) genotypes are associated with cognitive decline in PD . We performed a prospect i ve cohort study of 212 patients with a clinical diagnosis of PD . The primary outcome was change in Mattis Dementia Rating Scale version 2 score . Linear mixed-effects models and survival analysis were used to test for associations between genotypes and change in cognitive function over time . The ε4 allele of APOE was associated with more rapid decline ( loss of 2.9 ; 95 % confidence interval [ CI ] : 1.7 - 4.1 ) of more points per year ; P < 0.001 ) in total score and an increased risk of a ≥ 10 point drop during the follow-up period ( hazard ratio , 2.8 ; 95 % CI : 1.4 - 5.4 ; P = 0.003 ) . MAPT haplotype and COMT genotype were associated with measures of memory and attention , respectively , over the entire follow-up period , but not with the overall rate of cognitive decline . These results confirm and extend previously described genetic associations with cognitive decline in PD and imply that individual genes may exert effects on specific cognitive domains or at different disease stages . Carrying at least one APOE ε4 allele is associated with more rapid cognitive decline in PD , supporting the idea of a component of shared etiology between PD dementia and Alzheimer 's disease . Clinical ly , these results suggest that genotyping can provide information about the risk of future cognitive decline for PD patients Pyridoxal‐5‐phosphate , the biological active form of pyridoxine , is a cofactor for dopa‐decarboxylase ( DDC ) enzyme . Pyridoxine may augment the conversion of levodopa to dopamine in the periphery and therefore decrease availability of levodopa to the brain . However , this effect can be negated in the presence of a DDC inhibitor , which potentiates plasma levodopa level . A single nucleotide polymorphism at the nucleotide 1947 in the catechol‐O‐methyltransferase ( COMT ) gene encodes the high ( COMTH ) and low activity ( COMTL ) forms of the enzyme . In this study , we examined the effect of the COMTL allele on the clinical response to pyridoxine in Parkinson 's disease ( PD ) patients . PD patients who were on stable and optimized dose of levodopa were included in this study . Their mean motor and activities of living score improved after high dose pyridoxine ( P = 0.09 , P = 0.04 ) , and worsened after a washout period ( P = 0.005 , P = 0.001 ) . Using a multivariate model , the presence of the COMTL allele predicted response to pyridoxine , with the best outcome observed in COMTL/L homozygotes . Our observational study suggests that the status the functional COMTL variant may be potentially useful to select PD patients for high dose pyridoxine therapy . © 2005 Wiley‐Liss , Catechol-O-methyltransferase ( COMT ) is an enzyme that inactivates catecholamines such as adrenaline , noradrenaline , dopamine , and levodopa . Recently an amino acid change ( Val-108-Met ) of the COMT protein was found to determine high and low activity alleles of the COMT gene . We genotyped 109 Japanese patients with Parkinson 's disease ( PD ) and 153 controls by using polymerase chain reaction ( PCR ) amplification and digestion by the restriction enzyme NlaIII . The frequency of low activity allele in the controls was 0.29 , which was significantly different from that reported in Caucasians ( 0.50 ) . When comparison was made between patients with PD and controls , homozygosity for the low activity allele was significantly more common among the patients than among the controls ( P = 0.017 ; odds ratio , 2.8 , 95 % CI 1.2 - 6.5 ) , suggesting that homozygosity for the low activity allele may increase susceptibility to PD We explored the potential effect of catechol-O-methyltransferase ( COMT ) genetic polymorphism on the pharmacokinetics and pharmacodynamics of a st and ard oral dose of levodopa in patients with Parkinson 's disease ( PD ) . We prospect ively collected blood sample s for COMT genotyping from a population of 104 PD patients . Each patient was examined by a st and ard oral levodopa/benserazide test , based on simultaneous serial measurements of plasma levodopa concentrations , finger-tapping motor effects and dyskinesia ratings , up to 4 hours after dosing . The main levodopa pharmacokinetic outcome variables were time to peak and peak plasma concentration , plasma elimination half-life , and the area under the plasma concentration-time curve . The main outcome levodopa pharmacodynamic variables were latency , duration , and magnitude of the motor effect elicited by the levodopa test dose , the area under the tapping effect-time curve , and the presence of dyskinesias . Nineteen patients ( 18 % ) harbored the low-activity homozygous COMT genotype ( A/A ) , 63 patients ( 61 % ) carried the intermediate-activity heterozygous COMT genotype ( A/G ) and 22 patients ( 21 % ) had the high-activity homozygous COMT genotype ( G/G ) . The three groups were comparable for vital and clinical characteristics . No significant difference was found in levodopa main pharmacokinetic-pharmacodynamic variables and dyskinesia incidence among the three subgroups of patients . We failed to identify clinical ly relevant levodopa pharmacokinetic-pharmacodynamic response patterns associated with the COMT polymorphism in PD patients Objective To investigate the relationship between the catechol-O-methyltransferase ( COMT ) genotype and the therapeutic efficacy of entacapone . Methods The efficacy of 2 months of entacapone treatment in 65 patients with PD with end-of-dose deterioration was studied . The efficacy of entacapone was assessed using the Unified Parkinson ’s Disease Rating Scale ( UPDRS ) score , the daily levodopa dosage , and the patients ’ diary card . Results Thirty-six patients ( 55.4 % ) had a high-activity COMT gene ( COMTHH ) , 22 ( 33.8 % ) had an intermediate-activity COMT gene ( COMTHL ) , and 7 patients ( 10.8 % ) had a low-activity COMT gene ( COMTLL ) . Two months of entacapone treatment result ed in a significant increase in “ on ” time , a reduction in “ off ” time , and a reduction in the total UPDRS score , but these results were independent of the COMT genotype Output:	COMT genotypes could be related with a modest modification in the age at onset of PD , but its possible genotypes in excessive daytime somnolence , impulse control disorders , cognitive impairment , and neuropharmacological or neurochemical variables are unclear . The results of the meta- analysis suggest that the COMT rs4680 polymorphism is not a major determinant of either the risk for PD or clinical , neuropharmacological and neurochemical features of PD . Data on other COMT polymorphisms are scarce but do not suggest association with PD
MS212097	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: A double-blind , 18-center , balanced trial of diflunisal vs. cyclobenzaprine HCl vs. these two drugs combined vs. placebo produced complete results from 175 patients . They had sought treatment at the cooperating centers for acute painful spasms of the back within a day or two of trauma or strain . Global results over the 7 to 10 days of observations revealed a clinical ly and statistically significant superiority of the combined therapy by Day 4 ( P=0.006 ) and almost all patients recovered within a week to 10 days . A combination therapy with an effective safe analgesic and a true muscle relaxant for less than a week appears to be an excellent relief measure for acute back problems The reduction of pain by two antidepressants , clomipramine and mianserin , was , in this study on 253 patients with chronic idiopathic pain syndrome , found to be not better than a placebo when all patients were compared independently of the classification of pain . The improvement rate was around 40 % after 6 weeks of treatment when using a 50 % or better reduction in pain level . However , in patients who fulfilled a checklist definition of minor to major depression ( 30 % of the total patient material ) clomipramine was superior to mianserin and placebo with an improvement rate of 75 % after 6 weeks . Using pain curves over time as outcome measure in the various clinical pain categories it was found that both mianserin and clomipramine seemed superior to placebo in patients with tension headache , but in patients with low back pain syndrome placebo was superior to the two antidepressants . No difference among the three treatments was found in patients with burning mouth syndrome or in patients with abdominal pain . These differences underline the importance of study ing specific pain syndromes rather than composite groups of patients with idiopathic pain . The clinical significance of these pain curves needs further placebo controlled investigations & NA ; To assess the efficacy of nortriptyline , a tricyclic antidepressant , as an analgesic in chronic back pain without depression , we conducted a r and omized , double‐blind , placebo‐controlled , 8‐week trial in 78 men recruited from primary care and general orthopedic setting s , who had chronic low back pain ( pain at T‐6 or below on a daily basis for 6 months or longer ) . Of these 57 completed the trial ; of the 21 who did not complete , four were withdrawn because of adverse effects . The intervention consisted of inert placebo or nortriptyline titrated to within the therapeutic range for treating major depression ( 50–150 ng/ml ) . The main outcome endpoints were pain ( Descriptor Differential Scale ) , disability ( Sickness Impact Profile ) , health‐related quality of life ( Quality of Well‐Being Scale ) , mood ( Beck Depression Inventory , Spielberger State Anxiety Inventory , Hamilton Anxiety/Depression Rating Scales ) , and physician rated outcome ( Clinical Global Impression ) . Reduction in pain intensity scores was significantly greater for participants r and omized to nortriptyline ( difference in mean change 1.68 , 95 % −0.001 , CI −3.36 , P=0.050 ) , with a reduction of pain by 22 % compared to 9 % on placebo . Reduction in disability marginally favored nortriptyline ( P=0.055 ) , but health‐related quality of life , mood , and physician ratings of overall outcome did not differ significantly between treatments . Subgroup analyses of study completers supported the intent‐to‐treat analysis . Also , completers with radicular pain on nortriptyline ( n=5 ) had significantly ( P<0.05 ) better analgesia and overall outcome than did those on placebo ( n=6 ) . The results suggest noradrenergic mechanisms are relevant to analgesia in back pain . This modest reduction in pain intensity suggests that physicians should carefully weigh the risks and benefits of nortriptyline in chronic back pain without depression Thirty-seven patients with chronic back pain were entered into a r and omised , 3-way , double-blind , cross-over comparison of naproxen sodium 550 mg twice daily , diflunisal 500 mg twice daily , and placebo . Each treatment was given for 14 days after a preadmission wash-out week during which only paracetamol was allowed . Patients were assessed on admission and at the end of each treatment with respect to global pain , night pain , pain on movement , and pain on st and ing . Both visual analogue scales and simple descriptive scales were used to measure pain . Side effects were elicited by a nonleading question . Both methods of pain measurement gave similar results and were highly correlated . Naproxen sodium was superior to placebo in relieving global pain and depending on the method of measurement , in relieving night pain and pain on movement . Diflunisal showed no significant differences from placebo . Side effects were similar on all 3 treatments . The final preference of the patients was significantly in favour of the active treatments This report describes a double-blind between-group comparison of Tofranil and placebo in fifty-nine patients admitted to the Joint Service Medical Rehabilitation Unit suffering from low back pain . Patients were given 25 mg of either Tofranil or placebo three times a day for four weeks . Fifteen patients were not included in the analysis , nine dropping out for non-trial related reasons , two dropping out complaining of lost libido and four not taking the tablets , or taking additional drugs . One of the patients complaining of lost libido was taking Tofranil and the other was taking placebo . Over the whole sample there was no significant benefit for Tofranil over placebo as regards physical measurements . Both Tofranil and placebo groups showed a significant improvement during the trial on straight leg raise and backward flexion . For lateral flexion the Tofranil group was significantly worse than the placebo group on entering the trial , and during the trial the Tofranil group improved to match the placebo group . The clinician 's pain and stiffness assessment s and the patients ' pain and stiffness assessment s show a significant improvement for both the Tofranil and placebo groups during the trial . However , no difference is shown between Tofranil and placebo . The psychological tests show no difference between Tofranil and placebo and only a marinal improvenmet over initial condition . Further analysis according to initial diagnosis showed nothing conclusive . Numerically , the use of Tofranil produced a marked improvement in pain and stiffness in patients with ' disc lesion only ' diagnoses , whereas placebo did not produce an improvement . However , this observation was far from reaching statistical significance . Side-effects were not severe for either drug . Additional medication was rarely used The effectiveness of cyclobenzaprine hydrochloride , a new tricyclic skeletal muscle relaxant , was shown in patients with long-term intractable pain of cervical and lumbar origin aggravated by skeletal muscle spasm and tenderness . The investigation was double-blind and r and omized , comparing cyclobenzaprine hydrochloride ( 10 mg three times a day ) with diazepam ( 5 mg three times a day ) and with placebo . After two weeks of treatment , the 16 patients in the cyclobenzaprine group showed an overall improvement in pain variables as did the 16 patients in the diazepam group . No serious adverse reactions to cyclobenzaprine were observed in the study . However , dry mouth due to cyclobenzaprine 's anticholinergic action and mild degrees of drowsiness were encountered more often than with diazepam or placebo Thirty-nine patients with acute low back pain were treated with amitriptyline ( 150 mg/d ) or acetaminophen ( 2,000 mg/d ) in a controlled double-blind design for 5 weeks . Both groups revealed mild depression , normal coping , and increased anxiety at the beginning , with significant improvement in anxiety state and pain at the end of treatment . A repeated measures analysis of variance demonstrated that amitriptyline was more effective than acetaminophen in reducing pain intensity from the second week of treatment . Age and depression were the only significant pretreatment predictors of posttreatment pain . The study evaluates the significance of these findings Health status measures are being used with increasing frequency in clinical research . Up to now the emphasis has been on the reliability and validity of these measures . Less attention has been given to the sensitivity of these measures for detecting clinical change . As health status measures are applied more frequently in the clinical setting , we need a useful way to estimate and communicate whether particular changes in health status are clinical ly relevant . This report considers effect sizes as a useful way to interpret changes in health status . Effect sizes are defined as the mean change found in a variable divided by the st and ard deviation of that variable . Effect sizes are used to translate “ the before and after changes ” in a “ one group ” situation into a st and ard unit of measurement that will provide a clearer underst and ing of health status results . The utility of effect sizes is demonstrated from four different perspectives using three health status data sets derived from arthritis population s administered the Arthritis Impact Measurement Scales ( AIMS ) . The first perspective shows how general and instrument-specific benchmarks can be developed and how they can be used to translate the meaning of clinical change . The second perspective shows how effect sizes can be used to compare traditional clinical measures with health status measures in a st and ard clinical drug trial . The third application demonstrates the use of effect sizes when comparing two drugs tested in separate drug trials and shows how they can facilitate this type of comparison . Finally , our health status results show how effect sizes can supplement st and ard statistical testing to give a more complete and clinical ly relevant picture of health status change . We conclude that effect sizes are an important tool that will facilitate the use and interpretation of health status measures in clinical research in arthritis and other chronic diseases Twenty-seven investigators participated in a double-blind , parallel placebo-controlled trial of piroxicam involving 278 patients with acute low back pain . Therapy commenced within 48 hours of the injury and continued for 7 days . The drug was given in the recommended regimen of 40 mg once daily for the first 2 days and 20 mg once daily thereafter . After 3 days of therapy , piroxicam patients showed a statistically greater amount of pain relief in the lying ( P<0.001 ) , sitting ( P<0.01 ) , and st and ing ( P<0.01 ) positions , but after 7 days the difference between treatments was no longer significant . After 1 week 's therapy , however , the requirement for additional analgesic was significantly lower in the piroxicam group ( P<0.05 ) , and more piroxicam than placebo patients ( 42 versus 28 ) had returned to work ( P<0.05 ) . Toleration was excellent in most patients , with only 13 % of the piroxicam and 17 % of the placebo group reporting adverse effects of mainly mild or moderate severity . The profile of the adverse effects was similar for both treatments . Piroxicam can provide effective relief of acute low-back pain with good toleration ; it should be considered for use in the initial treatment of this condition A new drug , Cyclobenzaprine hydrochloride ( Flexeril ) , was compared with diazepam ( Valium ) and placebo in double-blind trials for efficacy in treating spasms and pain in the neck and low back . Complex recording methods involving clinical evaluations ( grade d ) , patient self-ratings , goniometry , motion analysis by computer , electromyography of controlled motions and detailed statistical analysis were used . Clinical improvement over two weeks was statistically significant in all treatment groups with a statistically significant preference for Cyclobenzaprine hydrochloride . The most striking improvements recorded were in the electromyographic findings , which showed statistically significant changes for the Cyclobenzaprine group . Clinical muscle spasms are not accompanied by increased myoelectric activity ; the reverse is true . With improvement , myoelectric activity in back muscles is augmented during prescribed stressful movements as measured by electromyography and computer analysis combined with complex electrogoniometry Chronic low back pain is a common problem that has been noted in several studies to exist as a component of masked depression . To determine the usefulness of imipramine in the treatment of chronic low back pain , either by a direct action or indirectly via resolution of a depressive equivalent , 50 consecutive patients were entered into a controlled trail that employed serum imipramine and desipramine levels and Beck depression question naires . Forty-one patients completed the study , and 48 were used in the statistical analysis . Imipramine had a statistically significant effect over placebo in most , but not all , of the clinical parameters that were measured . A linear relationship between serum drug levels and reported symptoms was not noted . Only 10 of the 50 patients entered into the study were judged clinical ly depressed and , of these , 7 were depressed according to st and ard criteria . There was no statistically significant difference noted in either the initial or the change in Beck depression scores between those on imipramine and those on placebo . However , among those on the active drug , the patients with a greater symptomatic response had a simultaneous change in the total Beck depression scores ( toward less depression ) that approached statistical significance when compared with those with a less symptomatic response . Although the results are not conclusive , imipramine may possibly be useful in the treatment of chronic low back pain , especially so when it exists as a component of masked depression Two groups of 20 patients each , with mild to moderate acute low back pain with associated muscle spasm of ten days ' duration or less , were treated with a combination of cyclobenzaprine and naproxen or naproxen alone in a r and omized , 14-day open-label trial . Cyclobenzaprine was added to the naproxen regimen as an adjunct to rest and physical therapy for relief of muscle spasm associated with acute , painful , musculoskeletal conditions . The clinical characteristics of each study group , including the number of worker 's compensation patients , were comparable . Combination therapy was associated with less objective muscle spasm and tenderness and greater motion of the lumbosacral spine ( P less than 0.05 ) . There were tr Output:	Treatment efficacy for these 5 outcomes was greatest early , in the first few days of treatment , declining after the first week . Patients receiving cyclobenzaprine also experienced more adverse effects , the most common being drowsiness . CONCLUSIONS Cyclobenzaprine is more effective than placebo in the management of back pain ; the effect is modest and comes at the price of greater adverse effects . The effect is greatest in the first 4 days of treatment , suggesting that shorter courses may be better .
MS212098	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVES The objectives of this study were to describe our laparoscopic nerve-sparing radical hysterectomy ( LNSRH ) technique and to assess the feasibility and safety of the procedure , as well as its impact on voiding function . We introduce a fascia space dissection technique in order to preserve the pelvic splanchnic nerve , the hypogastric nerve and the bladder branch of the inferior hypogastric plexus under magnification ( ×10.5 ) during laparoscopic radical hysterectomy ( LRH ) with pelvic lymphadenectomy . METHODS From October 2006 to November 2009 , 163 consecutive patients with cervical cancer underwent laparoscopic radical hysterectomy ( LRH ) and pelvic lymphadenectomy , with 82 women undergoing LNSRH with fascia space dissection technique ( LNSRH group ) and 81 undergoing LRH ( LRH group ) . Data from 163 patients were prospect ively collected and compared . Post-operative assessment of bladder function included the following : the time to recover the ability to void spontaneously and to achieve a post-void residual urine ( PVR ) volume of less than 50 ml , with urination function grade d. RESULTS The laparoscopic nerve-sparing radical hysterectomy procedure was completed successfully and was conducted safely in all of the patients . There were no conversions to open surgery in the two groups . The median operative duration in the LNSRH and the LRH groups were 163.52±34.47 min and 132.13±31.42 min , respectively . Blood loss was 142.12±62.38 ml and 187.69±68.63 ml , respectively . The time taken to obtain a post-void residual urine volume of less than 50 ml after removal of the urethral catheter was 7.42±2.35 d ( 5 - 18 d ) in LNSRH group and was 16.75±7.73 d ( 5 - 35 d ) in LRH group ( P<0.05 ) . The bladder void function recovery to Grade s 0-I was 76 ( 92.7 % ) for the LNSRH group and 59 ( 72.8 % ) for the LRH group . A mean follow-up of 22.3 ( 5 - 42 ) months was adhered to , and no patient had a recurrence or metastasis . CONCLUSIONS The technique described in this preliminary study appears to be safe , feasible , and easy in our population , with satisfactory recovery of voiding function OBJECTIVE To investigate bladder and intestinal function recovery and quality of sexual life after laparoscopic nerve-sparing radical hysterectomy ( LNRH ) for treatment of early invasive cervical carcinoma . METHODS Subjects included patients who underwent radical hysterectomy by laparotomy who were r and omly assigned to 2 groups : 30 patients who underwent LNRH and 35 classical laparoscopic radical hysterectomy ( LRH ) . We assessed the patients general clinical information , surgical characteristics , pathological findings , and adjuvant therapies . A urodynamic study was used to assess bladder function . Intestinal function recovery and quality of sexual life were evaluated by question naire . RESULTS No significant differences were found in age , surgery characteristics , pathological findings , adjuvant therapies , and main adverse effects between the 2 groups . The mean duration of the postoperative catheterization ( DPC ) in group LNRH was shorter than that in group LRH ( P < 0.001 ) . The maximum flow rate , maximum cystometric capacity , maximum detrusor pressure and urinary complications in group LNRH were better than those in group LRH . The quality of sexual life evaluated according to the female sexual function index ( FSFI ) was better in group LNRH than in those who underwent LRH . The intestinal function of patients in group LNRH also recovered better compared with patients in group LRH The objective of this study is to describe a technique for preserving the autonomic nerve systematic ally , including the hypogastric nerves , pelvic splanchnic nerves , and pelvic plexus and its vesical branches , based on anatomic considerations for the autonomic nerves innervating the urinary bladder , in radical hysterectomies and to assess postsurgical bladder function . A nerve-sparing radical hysterectomy was carried out on 27 consecutive patients with uterine cervical cancer treated between 2000 and 2002 . The FIGO stages of the disease consisted of 10 stage Ib1 , 6 stage Ib2 , 3 stage IIa , and 8 stage IIb . The nerve-sparing procedure was successfully completed in 22 of the 27 patients ( 81.5 % ) in the study . At 1 year after the operation , bladder symptoms were significantly improved in the nerve-sparing group compared to the non – nerve-sparing group . Urinary incontinence and abnormal ( diminished ) bladder sensation were observed in three of the five patients ( two patients had both symptoms ) , for whom the nerve-sparing procedure could not be performed , but none of the 22 patients for whom the nerve-sparing procedure was performed had incontinence , and only two patients had abnormal ( increased ) bladder sensation ( P = 0.0034 for incontinence and P = 0.030 for abnormal bladder sensation ) . The patients ' survival was not adversely affected by the nerve-sparing procedure . Although it is still preliminary , the surgical technique described in this report is thought to be effective for preserving bladder function , and thus , the quality of life could be improved for patients with cervical cancer who are treated with a radical hysterectomy . For further evaluation of the efficacy of nerve-sparing radical hysterectomy , a prospect i ve r and omized trial needs to be performed Objective Conventional radical hysterectomy with pelvic lymphadenectomy ( RHL ) for early-stage cervical cancer is associated with significant bladder , anorectal , and sexual dysfunction . Nerve-sparing modification of RHL ( NS-RHL ) has been developed with the aim to reduce surgical treatment-related morbidity . Postoperative radiation therapy ( RT ) is offered to patients with unfavorable prognostic features to improve local control . The aim of the study was to assess self-reported morbidity of various types of treatment in cervical cancer patients . Methods Self-reported symptoms were prospect ively assessed before and 1 and 2 years after treatment by the Dutch Gynaecologic Leiden Question naire . Results Included were 229 women ( 123 NS-RHL and 106 conventional RHL ) . Ninety-four ( 41 % ) received RT . Up to 2 years ( response rate , 81 % ) , women reported significantly more bowel , bladder , and sexual symptoms compared with the pretreatment situation . No significant difference was found between the conventional RHL and NS-RHL with the exception of the unexpected finding that a smaller percentage in the NS-RHL group ( 34 % vs 68 % ) complained about numbness of the labia and / or thigh . Radiation therapy had a negative impact on diarrhea , urine incontinence , lymphedema , and sexual symptoms ( especially a narrow/short vagina ) . Conclusions In the current longitudinal cohort study , treatment for early-stage cervical cancer was associated with worse subjective bladder , anorectal , and sexual functioning , irrespective of the surgical procedure used . Postoperative RT result ed in a significant deterioration of these functions . The results have to be interpreted with caution in view of the study design and method used Introduction : The present study compares for the first time the st and ard therapy for cervical cancer in FIGO-stages IB-IIB , radical hysterectomy according to the Wertheim-Meigs operation , with the newly developed , nerve-sparing surgical technique , total mesometrial resection ( TMMR ) with regard to postoperative , health-related quality of life . Method : In the framework of a multicentre , retrospective cohort study a total of 110 cervical cancer patients were interviewed once by means of the European Organisation for Research and Treatment of Cancer Quality of Life Question naire ( EORTC QLQ-C30 ) and the cervical cancer module ( EORTC QLQ-CX24 ) . The influence of the surgical method was investigated by analysis of covariance under control of age and the time elapsed between treatment and interview . Results : An influence of the therapeutic method was demonstrated in the EORTC scales physical function ( p = 0.047 ) , role function ( p = 0.016 ) , fatigue ( p = 0.028 ) , pain ( p = 0.018 ) , shortness of breath ( p = 0.034 ) , lack of appetite ( p = 0.006 ) and diarrhoea ( p = 0.012 ) in favour of the 74 women treated by TMMR . With regard to cognitive , emotional and social functioning as well as cervical cancer-specific symptoms , no significant differences between the therapy groups were found . Conclusion : The findings presented in this study suggest a superiority of TMMR in comparison to the previously employed radical hysterectomy according to Wertheim-Meigs with regard to the postoperative quality of life , especially in the fields of physical activity and fatigue . This needs to be vali date d in the course of prospect i ve , multicentre studies . In addition , it must be clarified as to what extent the found effects are , in particular , due to the omission of an additional radiotherapy OBJECTIVE Surgical therapy for cervical carcinoma carries a significant risk of functional impairment to the bladder . This study evaluates the feasibility and complications of nerve-sparing radical hysterectomy ( NRH ) in Taiwan . METHODS Between March 2010 and March 2011 , consecutive patients diagnosed with early stage cervical cancer ( FIGO stage Ia2 to Ib1 ) and tumor size < 3 cm were recruited prospect ively to undergo NRH or conventional radical hysterectomy ( RH ) . Patients with histories of urinary stress incontinence or bladder dysfunction disease were excluded . A modified Tokyo nerve-sparing radical hysterectomy was performed . RESULTS A total of 30 patients were enrolled . Among these , 18 patients underwent NRH with successful bilaterally nerve-sparing procedures in 15 cases ( 83 % ) , unilaterally nerve-sparing procedures in 2 cases ( 11 % ) , and a failure in 1 case ( 6 % ) . The indwelling catheter was removed on postoperative day 6 . The mean±SD duration from operation to spontaneous voiding was 6.8 ± 1.5 days for women who underwent NRH ; the corresponding duration for women who underwent RH or failed NRH was 20.6 ± 3 days . None of the patients who underwent NRH required intermittent catheterization . All 12 patients who underwent RH needed self-catheterization after discharge . There was a significant reduction in the incidence of postoperative self-catheterization ( p<0.01 ) and bladder dysfunction ( p<0.006 ) . Average satisfaction score analyzed by the Likert-scale question naire was 4.5 for the NRH group and 1.9 for RH group ( p<0.0001 ) . CONCLUSIONS We concluded that the new technique of NRH can reduce postoperative bladder dysfunctions OBJECTIVE To assess the nerve-sparing radical hysterectomy ( NSRH ) technique and its impact on postoperative voiding function . METHODS Forty-four patients with International Federation of Gynecology and Obstetrics ( FIGO ) stage I b1-IIa cervical cancer were enrolled and r and omized into NSRH group ( study group , n = 22 ) and conventional radical hysterectomy ( CRH ) group ( control group , n = 22 ) . The pelvic autonomic nerve pathway ( including hypogastric nerve , pelvic splanchnic nerve , inferior hypogastric plexus and bladder branch ) was completely preserved in the NSRH group . Related parameters were compared between the two groups . RESULTS The estimated blood loss in NSRH group and CRH group were ( 550 + /- 241 ) ml and ( 475 + /- 284 ) ml , respectively , with no significant difference ( P > 0.05 ) . The mean operation time in NSRH group and CRH group were ( 329 + /- 43 ) min and ( 272 + /- 56 ) min , respectively , with a significant difference ( P < 0.01 ) . More patients in NSRH group had post-void residual urine volume ( PVR ) < 100 ml than that in CRH group on day 8 after surgery ( 68 % vs. 18 % , P < 0.01 ) . The median duration of postoperative catheterization was significantly shorter in NRSH group ( 8 - 23 days , median 8 days ) than that in CRH group ( 8 - 32 days , median 20 days ; P < 0.01 ) . Neither surgery-related injury nor pathologically positive margin was reported in either of the groups . CONCLUSIONS NSRH is a feasible and safe technique for preserving bladder function . Larger prospect i ve studies are needed to confirm the efficacy of this technique Objective : To investigate the bladder function recovery and quality of life ( QOL ) using nerve-sparing radical hysterectomy ( NSRH ) in treating early invasive cervical carcinoma . Output:	Meta- analysis demonstrated that NSRH was associated with less bladder and anorectal dysfunction than RH . The time to bladder and anorectal function recovery after NSRH was shorter than RH . Patients undergoing NSRH also scored higher than patients undergoing RH at Female Sexual Function Index ( FSFI ) . On the other h and , the local recurrence and overall recurrence rate were similar between NSRH and RH . Conclusion : NSRH may be an effective technique for lowering pelvic organ dysfunction and improving the function recovery without increasing the recurrence rate of cervical cancer
MS212099	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Introduction Recombinant granulocyte colony-stimulating factor ( G-CSF ) may aid engraftment post high-dose chemo-/radiotherapy in patients with haematological malignancies undergoing allogeneic bone marrow transplantation ( BMT ) ; however , the effects of G-CSF on graft-versus-host disease ( GvHD ) , relapse , and survival are not well defined . Methods In this double-blind , r and omized , placebo-controlled , multicentre , phase 3 study , the effects of the G-CSF Filgrastim on neutrophil and platelet recovery , and on clinical outcomes were evaluated . Patients ( 12–55 years ) receiving an allogeneic BMT for a haematological malignancy were r and omized to receive Filgrastim 5 µg/kg or placebo . Study treatment was continued until patients achieved an absolute neutrophil count ( ANC ) ≥0.5 × 109/L , or until day 42 . Results Fifty-one patients ( Filgrastim , N = 25 ; placebo , N = 26 ) were evaluable . Patients treated with Filgrastim had significantly faster engraftment with ANC ≥0.5 × 109/L being achieved after a median ( range ) of 15.0 ( 1.0–22.0 ) days vs. 19.0 ( 15.0–28.0 ) days for placebo ( P < 0.0001 ) . The incidence of GvHD was comparable for both groups . During the limited follow-up ( 2 years ) , Filgrastim had no adverse effect on mortality and possibly reduced the rate of relapse Purpose Pegfilgrastim is a pegylated form of filgrastim , a recombinant protein of granulocyte colony-stimulating factor , that is used to reduce the risk of febrile neutropenia ( FN ) . Here , we report the results of a phase III trial of pegfilgrastim in breast cancer patients receiving docetaxel and cyclophosphamide ( TC ) chemotherapy . Methods We conducted a double-blind , placebo-controlled , r and omized trial to determine the efficacy of pegfilgrastim in reducing the risk of FN in early-stage breast cancer patients . A total of 351 women ( 177 in the pegfilgrastim group and 174 in the placebo group ) between 20 and 69 years of age with stage I – III invasive breast carcinoma who were to receive TC chemotherapy ( docetaxel 75 mg/m2 and cyclophosphamide 600 mg/m2 every 3 weeks ) as either neoadjuvant or adjuvant therapy were enrolled ; 346 of these patients were treated with either pegfilgrastim ( n = 173 ) or placebo ( n = 173 ) . Results The incidence of FN was significantly lower in the pegfilgrastim group than in the placebo group ( 1.2 vs. 68.8 % , respectively ; P < 0.001 ) . In addition , patients in the pegfilgrastim group required less hospitalization and antibiotics for FN . Most adverse events were consistent with those expected for breast cancer subjects receiving TC chemotherapy . Conclusions Pegfilgrastim is safe and significantly reduces the incidence of FN in breast cancer patients Recombinant human granulocyte colony-stimulating factor ( G-CSF ; filgrastim ) shortens the time to neutrophil recovery after intensive chemotherapy , but its role in the treatment of adults with acute lymphoblastic leukemia ( ALL ) is uncertain . We r and omly assigned 198 adults with untreated ALL ( median age , 35 years ; range , 16 to 83 ) to receive either placebo or G-CSF ( 5 microgram/kg/d ) subcutaneously , beginning 4 days after starting intensive remission induction chemotherapy and continuing until the neutrophil count was > /=1 , 000/microL for 2 days . The study assignment was unblinded as individual patients achieved a complete remission ( CR ) . Patients initially assigned to G-CSF then continued to receive G-CSF through 2 monthly courses of consolidation therapy . Patients assigned to placebo received no further study drug . The median time to recover neutrophils > /=1,000/microL during the remission induction course was 16 days ( interquartile range [ IQR ] , 15 to 18 days ) for the patients assigned to receive G-CSF and 22 days ( IQR , 19 to 29 days ) for the patients assigned to placebo ( P < .001 ) . Patients in the G-CSF group had significantly shorter duration s of neutropenia ( < 1 , 000/microL ) and thrombocytopenia ( < 50,000/microL ) and fewer days in the hospital ( median , 22 days v 28 days ; P = .02 ) compared with patients receiving placebo . The patients assigned to receive G-CSF had a higher CR rate and fewer deaths during remission induction than did those receiving placebo ( P = .04 by the chi-square test for trend ) . During Courses IIA and IIB of consolidation treatment , patients in the G-CSF group had significantly more rapid recovery of neutrophils > /=1,000/microL than did the control group by approximately 6 to 9 days . However , the patients in the G-CSF group did not complete the planned first 3 months of chemotherapy any more rapidly than did the patients in the placebo group . Overall toxicity was not lessened by the use of G-CSF . After a median follow-up of 4 . 7 years , there were no significant differences in either the disease-free survival ( P = .53 ) or the overall survival ( P = .25 ) for the patients assigned to G-CSF ( medians , 2.3 years and 2.4 years , respectively ) compared with those assigned to placebo ( medians , 1.7 and 1.8 years , respectively ) . Adults who received intensive chemotherapy for ALL benefited from G-CSF treatment , but its use did not markedly affect the ultimate outcome Patients with non-myeloid hematologic malignancies ( including Hodgkin 's and non-Hodgkin 's lymphomas , myeloma and acute lymphoid leukemia ) or solid tumors underwent cytoreductive conditioning regimens followed by either autologous bone marrow transplantation ( ABMT ) ( n = 343 ) or transplantation of peripheral blood stem cells ( PBSC ) with ( n = 44 ) or without bone marrow ( BM ) ( n = 16 ) . In a r and omized double-blind phase III multi-center trial , patients received either granulocyte-macrophage colony-stimulating factor ( GM-CSF , 10 micrograms/kg/day ) or placebo by daily i.v . infusion beginning 24 h after bone marrow infusion and continuing until the absolute neutrophil count ( ANC ) had recovered to > or = 1000/mm3 , or for a maximum of 30 days . Median time to neutrophil recovery was significantly shorter in the GM-CSF group ( 18 vs 27 days , P < 0.001 ) , and more GM-CSF patients had neutrophil recovery by day 30 ( 70 vs 48 % ) . Median duration of hospitalization was significantly shorter in the GM-CSF group ( 29 vs 32 days , P = 0.02 ) . GM-CSF significantly reduced the median time to neutrophil recovery in patients receiving bone marrow only ( 19 vs 27 days , P < 0.001 ) or PBSC with or without bone marrow ( 14 vs 21 days , P < 0.001 ) . The overall incidence of adverse events was comparable in the two groups , although more patients in the GM-CSF group discontinued treatment due to adverse events ( 17 vs 9 % , P < 0.001 ) . No difference was noted in infection incidence or time to platelet independence . GM-CSF had no negative impact on time to relapse or long-term survival . These data indicate the positive influence of GM-CSF on neutrophil recovery and hospital stay in patients receiving ABMT for a variety of clinical indications BACKGROUND Neutropenia is common in patients receiving myelotoxic chemotherapy . Pegfilgrastim , a sustained- duration filgrastim is a once-per-cycle therapy for prophylactic neutrophil support . PATIENTS AND METHODS Women , treated with four cycles of doxorubicin/docetaxel chemotherapy every 21 days , received pegfilgrastim or filgrastim 24 h after chemotherapy as a single subcutaneous injection per chemotherapy cycle ( pegfilgrastim 30 , 60 or 100 microg/kg ) or daily subcutaneous injections ( filgrastim 5 microg/kg/day ) . Safety , efficacy and pharmacokinetics were analyzed . RESULTS The incidence of grade 4 neutropenia in cycle 1 was 95 , 90 and 74 % , in patients who received pegfilgrastim 30 , 60 and 100 microg/kg , respectively , and 76 % in patients who received filgrastim . Mean duration of grade 4 neutropenia in cycle 1 was 2.7,2 and 1.3 days for doses of pegfilgrastim , and 1.6 days for filgrastim . The pharmacokinetics of pegfilgrastim were non-linear and dependent on both dose and neutrophil count . Pegfilgrastim serum concentration was sustained until the neutrophil nadir occurred then declined rapidly as neutrophils started to recover , consistent with a self-regulating neutrophil-mediated clearance mechanism . The safety profiles of pegfilgrastim and filgrastim were similar . CONCLUSIONS A single subcutaneous injection of pegfilgrastim 100 microg/kg provided neutrophil support and a safety profile comparable to daily subcutaneous injections of filgrastim during multiple chemotherapy cycles In order to evaluate the potential clinical and economic benefits of granulocyte colony-stimulating factor ( G-CSF , filgrastim ) following peripheral blood progenitor cells ( PBPC ) rescue after high-dose chemotherapy ( HDCT ) , 23 consecutive patients aged less than 60 years with poor-prognosis , high- grade non-Hodgkin 's lymphoma ( NHL ) were entered into a prospect i ve r and omized trial between May 1993 and September 1995 . Patients were r and omized to receive either PBPC alone ( n = 12 ) or PBPC+G-CSF ( n = 11 ) after HDCT with busulphan and cyclophosphamide . G-CSF ( 300 microg day[-1 ] ) was given from day + 5 until recovery of granulocyte count to greater than 1.0 x 10(9 ) l(-1 ) for 2 consecutive days . The mean time to achieve a granulocyte count > 0.5 x 10(9 ) l(-1 ) was significantly shorter in the G-CSF arm ( 9.7 vs 13.2 days ; P<0.0001 ) as was the median duration of hospital stay ( 12 vs 15 days ; P = 0.001 ) . In addition the recovery periods ( range 9 - 12 vs 11 - 17 days to achieve a count of 1.0 x 10(9 ) l[-1 ] ) and hospital stays ( range 11 - 14 vs 13 - 22 days ) were significantly less variable in patients receiving G-CSF in whom the values clustered around the median . There were no statistically significant differences between the study arms in terms of days of fever , documented episodes of bacteraemia , antimicrobial drug usage and platelet/red cell transfusion requirements . Taking into account the costs of total occupied-bed days , drugs , growth factor usage and haematological support , the mean expenditure per inpatient stay was pound sterling 6500 ( range pound sterling 5465-pound sterling 8101 ) in the G-CSF group compared with pound sterling 8316 ( range pound sterling 5953-pound sterling 15,801 ) in the group not receiving G-CSF , with an observed mean saving of 1816 per patient ( or 22 % of the total cost ) in the G-CSF group . This study suggests that after HDCT and PBPC rescue , the use of G-CSF leads to more rapid haematological recovery periods and is associated with a more predictable and shorter hospital stay . Furthermore , and despite the additional costs for G-CSF , these clinical benefits are not translated into increased health care expenditure BACKGROUND Immunological and clinical effects of post-transplant growth factor administration have not been well studied . This report describes the outcome and immune functions of a total of 50 HLA-matched related donor allogeneic blood stem-cell transplantation patients who received post-transplant G-CSF ( 10 microg/kg ) or placebo . METHODS Immune status , including number of lymphocyte subsets and their functions , and serum immunoglobulin levels and clinical status -- including GvHD , rate of relapse , event-free survival , and overall survival -- were determined in the patients enrolled in this study . RESULTS Twenty-eight patients survived 1 year after transplant , and 15 patients had available results to compare immune function by r and omization assignment . At 12 months post-transplant , immune parameters in G-CSF versus placebo groups showed no statistically significant differences in number of circulating lymphocyte subsets CD3 , CD4 , CD8 , CD19 and CD56 in the two groups . There was no significant ( NS ) difference Output:	There was no evidence of a difference in terms of median survival time in the trial comparing GM-CSF and antibiotics .

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