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Clinical NLP Lab 26

MS214100

***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 Cardiovascular disease ( CVD ) and diabetes account for one-third of the mortality difference between African American and white patients . We evaluated the effect of a CVD risk reduction intervention in African Americans with diabetes . METHODS We r and omized 359 African Americans with type 2 diabetes to receive usual care or a nurse telephone intervention . The 12-month intervention provided monthly self-management support and quarterly medication management facilitation . Co primary outcomes were changes in systolic blood pressure ( SBP ) , hemoglobin A1c ( HbA1c ) , and low-density lipoprotein cholesterol ( LDL-C ) over 12 months . We estimated between-intervention group differences over time using linear mixed-effects models . The secondary outcome was self-reported medication adherence . RESULTS The sample was 72 % female ; 49 % had low health literacy , and 37 % had annual income < $ 10,000 . Model-based estimates for mean baseline SBP , HbA1c , and LDL-C were 136.8 mm Hg ( 95 % CI 135.0 - 138.6 ) , 8.0 % ( 95 % CI 7.8 - 8.2 ) , and 99.1 mg/dL ( 95 % CI 94.7 - 103.5 ) , respectively . Intervention patients received 9.9 ( SD 3.0 ) intervention calls on average . Primary providers replied to 76 % of nurse medication management facilitation contacts , 18 % of these result ed in medication changes . There were no between-group differences over time for SBP ( P = .11 ) , HbA1c ( P = .66 ) , or LDL-C ( P = .79 ) . Intervention patients were more likely than those receiving usual care to report improved medication adherence ( odds ratio 4.4 , 95 % CI 1.8 - 10.6 , P = .0008 ) , but adherent patients did not exhibit relative improvement in primary outcomes . CONCLUSIONS This intervention improved self-reported medication adherence but not CVD risk factor control among African Americans with diabetes . Further research is needed to determine how to maximally impact CVD risk factors in African American patients Background — Even in high-performing health systems , some patients with diabetes mellitus have poor blood pressure ( BP ) control because of poor medication adherence and lack of medication intensification . We examined whether the Adherence and Intensification of Medications intervention , a pharmacist-led intervention combining elements found in efficacy studies to lower BP , improved BP among patients with diabetes mellitus with persistent hypertension and poor refill adherence or insufficient medication intensification in 2 high-performing health systems . Methods and Results — We conducted a prospect i ve , multisite cluster r and omized pragmatic trial with r and omization of 16 primary care teams at 5 medical centers ( 3 Veterans Affairs and 2 Kaiser Permanente ) to the Adherence and Intensification of Medications intervention or usual care . The primary outcome was relative change in systolic BP ( SBP ) , comparing 1797 intervention with 2303 control team patients , from 6 months preceding to 6 months after the 14-month intervention period . We examined shorter-term changes in SBP as a secondary outcome . The mean SBP decrease from 6 months before to 6 months after the intervention period was ≈9 mm Hg in both arms . Mean SBPs of eligible intervention patients were 2.4 mm Hg lower ( 95 % CI : −3.4 to −1.5 ; P<0.001 ) immediately after the intervention than those achieved by control patients . Conclusions — The Adherence and Intensification of Medications program more rapidly lowered SBPs among intervention patients , but usual-care patients achieved equally low SBP levels by 6 months after the intervention period . These findings show the importance of evaluating in different real-life clinical setting s programs found in efficacy trials to be effective before urging their widespread adoption in all setting s. Clinical Trial Registration — URL : http:// clinical trials.gov . Unique identifier : NCT00495794 Background : Diabetes mellitus ( DM ) requires continuous medical care , patients ’ self-management , education , and adherence to prescribed medication to reduce the risk of long-term complications . The aim of this study was to assess the benefits of an education program on diabetes , patient self-management , adherence to medication , anxiety , depression and glycemic control in type 2 diabetics in Saudi Arabia . Material s and Methods : This was a prospect i ve study , conducted among 104 diabetic patients at a major tertiary hospital in Riyadh , Saudi Arabia , between May 2011 and October 2012 . Education material s given to diabetic patients included pamphlets/h and outs written in Arabic , the national language . Special videotapes about DM were made and distributed to all participants . In addition , specific educational programs through the diabetes educators and one-on-one counseling sessions with the doctor were also arranged . Patients were interviewed using a structured interview schedule both during the baseline , and after 6 months of the program . The interview schedule included , socio-demographics , clinical characteristics , diabetes self-management , adherence to medication , anxiety , and depression . Glycemic control was considered poor , if hemoglobin A1c ( HbA1c ) was ≥ 7 % . Results : The mean age of the study population was 57.3 ± 14.4 years . Seventy one were males ( 68.3 % ) and 33 ( 31.7 % ) were females . After six months of the diabetes education program , there were significant improvements in patients ’ dietary plan ( P = 0.0001 ) , physical exercise ( P = 0.0001 ) , self-monitoring of blood glucose ( SMBG ) ( P = 0.0001 ) , HbA1c ( P = 0.04 ) , adherence to medication ( P = 0.007 ) , and depression ( P = 0.03 ) . Conclusions : Implementation of education programs on diabetes among type 2 diabetic patients is associated with better outcomes such as their dietary plan , physical exercise , SMBG , adherence to medication , HbA1c and depression AIM To compare the effectiveness of two methods of follow-up : short message service and telephone follow-up on type 2 diabetes adherence for three months . BACKGROUND Using telemedicine approaches may preserve appropriate blood glucose levels and may improve adherence to diabetes control recommendations in diabetic patients . DESIGN A quasi-experimental , two-group , pretest and post-test design was used in this study to evaluate the effectiveness of nurse 's follow-up via cellular phones and telephones . METHODS The sample consisted of 77 patients with type 2 diabetes that r and omly were assigned to two groups : telephone follow-up ( n = 39 ) and short message service ( n = 38 ) . Telephone interventions were applied by a research er for three months ; twice a week for the first month and every week for the second and third month . For three successive months , the short message service group that received messages about adherence to therapeutic regimen was examined . The data gathering instrument included data sheets - to record glycosylated haemoglobin - and the question naire related to adherence therapeutic regimen . Data gathering was carried out at the beginning of the study and after three and six months . The data were analysed using descriptive and inferential statistic methods with SPSS version 11.5 . RESULTS Results showed that both interventions had significant mean changes in glycosylated haemoglobin . For the telephone group ( p < 0.001 ) , a mean change of -0.93 and for the short message service group ( p < 0.001 ) , a mean change of -1.01 . There was no significant difference in diet adherence ( p = 0.000 ) , physical exercise ( p = 0.000 ) and medication taking ( p = 0.000 ) adherence in either groups . CONCLUSION Intervention using short message services of cellular phones and nurse-led-telephone follow-up improved HbA1c levels and adherence to diabetes therapeutic regimen for three months in type 2 diabetic patients . RELEVANCE TO CLINICAL PRACTICE Both of follow-up intervention uses in this study can decrease HbA1c levels and escalate adherence to diabetes control recommendations in people with type 2 diabetes for three months BACKGROUND Peripheral arterial disease patients are less likely than other high-risk patients to achieve ideal low-density lipoprotein ( LDL ) cholesterol levels . This r and omized controlled trial assessed whether a telephone counseling intervention , design ed to help peripheral arterial disease patients request more intensive cholesterol-lowering therapy from their physician , achieved lower LDL cholesterol levels than 2 control conditions . METHODS There were 355 peripheral arterial disease participants with baseline LDL cholesterol ≥70 mg/dL enrolled . The primary outcome was change in LDL cholesterol level at 12-month follow-up . There were 3 parallel arms : telephone counseling intervention , attention control condition , and usual care . The intervention consisted of patient-centered counseling , delivered every 6 weeks , encouraging participants to request increases in cholesterol-lowering therapy from their physician . The attention control condition consisted of telephone calls every 6 weeks providing information only . The usual care condition participated in baseline and follow-up testing . RESULTS At 12-month follow-up , participants in the intervention improved their LDL cholesterol level , compared with those in attention control ( -18.4 mg/dL vs -6.8 mg/dL , P=.010 ) but not compared with those in usual care ( -18.4 mg/dL vs -11.1 mg/dL , P=.208 ) . Intervention participants were more likely to start a cholesterol-lowering medication or increase their cholesterol-lowering medication dose than those in the attention control ( 54 % vs 18 % , P=.001 ) and usual care ( 54 % vs 31 % , P < .001 ) conditions . CONCLUSION Telephone counseling that helped peripheral arterial disease patients request more intensive cholesterol-lowering therapy from their physician achieved greater LDL cholesterol decreases than an attention control arm that provided health information alone AIMS To determine whether an extended pharmacy service would improve glycaemic control and cardiovascular risks in diabetic Muslims . METHODS Ambulatory literate adult diabetic Muslims with A1C > 7 % were r and omly assigned to either a study group ( usual care plus added pharmacist input , N=63 ) or a control group ( usual care only , N=67 ) . On four consecutive visits , at 2-month intervals , the study group met a pharmacist who educated and discussed with each patient regarding medication uses and diabetic treatment . This was accompanied by providing a diabetic pamphlet . Changes in A1C ( mg/dL ) , lipid parameters ( mg/dL ) , medication adherence ( % pill count ) and diabetic knowledge scores were measured . RESULTS There was no difference in A1C reduction between the study and the control groups ( -0.8 vs. -0.6 , p=0.56 ) . Total cholesterol and LDL-C improvements were greater in the study group than in the control group ( -31.6 vs. -1.2 , p=0.000 ; -15.0 vs. + 9.1 , p=0.002 , respectively ) . The percent pill count ( + 6.8 vs. -2.8 , p=0.004 ) and diabetic knowledge scores ( + 2.1 vs. + 0.6 , p=0.002 ) were increased in the study group but not in the control group . CONCLUSION The pharmacist ' s one-on-one education on diabetes accompanied by its pamphlet , in Muslim patients with diabetes did not affect glycaemic outcome but reduction in cardiovascular risks through lowering total cholesterol and LDL-C was found . The strategies may also improve diabetic knowledge and medication adherence We studied the effects of home telemonitoring in elderly patients with congestive heart failure ( CHF ) on mortality and rate of hospitalization , compliance with treatment , quality of life and costs of CHF management , by comparison with a group receiving usual care . Fifty-seven elderly CHF patients were r and omized to st and ard care or to home telemonitoring-based care and followed for 12 months . In the subjects who were monitored , weekly reports on their clinical status were obtained and their management was modified accordingly . Home telemonitoring was associated with improvements in the composite endpoint of mortality and rate of hospitalizations ( P = 0.006 ) , a better compliance with therapy , more frequent use of beta-blockers and statins , lower total cholesterol level and a better reported health perception score . The improved results with home telemonitoring in CHF were probably due to better compliance and to closer monitoring of the patients OBJECTIVE To examine the effect of a 12-month pharmaceutical care ( PC ) program on vascular risk in type 2 diabetes . RESEARCH DESIGN AND METHODS We recruited 198 community-based patients r and omized to PC or usual care . PC patients had face-to-face goal -directed medication and lifestyle counseling at baseline and at 6 and 12 months plus 6-weekly telephone assessment s and provision of other educational material . C Output:

The preponderance of evidence suggests a positive impact of PSPs on adherence , clinical and humanistic outcomes . Although less often measured , health care utilization and costs are also reduced following PSP implementation .

MS214101

***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: Eleven women with a history of infertility and uterine leiomyomas underwent magnetic resonance ( MR ) imaging of the pelvis prior to myomectomy . Nine also underwent preoperative pelvic ultrasonography ( US ) , and ten underwent hysterosalpingography . All studies were interpreted prospect ively by independent observers . With each imaging modality , the location ( one of 11 anatomic segments ) , size , and appearance of detected uterine leiomyomas were determined and compared with surgical and histologic findings . Among the nine patients who underwent both MR and US , the sensitivity ( 85 % ) and accuracy ( 94 % ) of MR imaging for abnormal segments was significantly better than that of US ( sensitivity = 69 % , P = .015 ; accuracy = 87 % , P = .043 ) . For the ten patients who underwent both MR and hysterosalpingography , the sensitivity ( 91 % ) and accuracy ( 96 % ) of MR imaging was better than that of hysterosalpingography ( sensitivity = 18 % , P = .0005 ; accuracy = 72 % , P = .0005 ) . The specificities of the three modalities did not significantly differ ( 100 % , 97 % , and 98 % for MR , US , and hysterosalpingography , respectively ) . These data suggest that MR imaging is superior to US or hysterosalpingography for preoperatively locating uterine leiomyomas BACKGROUND Several studies have reported that the presence of intramural fibroids affects conception following IVF . We attempted to corroborate or refute the conclusions relating to IVF and leiomyomas of the aforementioned studies . METHODS Women with small intramural leiomyomata ( < or = 5 cm ) discovered on initial pelvic sonographic studies performed in preparation for IVF were prospect ively matched by age , with the next patient of the same age undergoing IVF who did not demonstrate fibroids ( controls ) . RESULTS Though no significant differences were found in outcome when comparing these two groups , there was a distinct trend for lower live delivery rates and higher miscarriage rates . CONCLUSIONS These data support the conclusions of the only other prospect i ve matched control study evaluating similar factors , i.e. that small intramural fibroids can negatively affect IVF outcome . Nevertheless , we think that a multicentre study should be conducted first before evaluating whether myomectomy improves outcome or not Objective To assess the usefulness of transabdominal sonohysterography in the diagnosis and evaluation of submucous myomas . Methods Fifty-two premenopausal women hospitalized for hysterectomy for benign gynecologic indications under-went preoperative conventional transvaginal sonography , transabdominal sonohysterography , and hysteroscopy . The results of the three techniques in terms of diagnosis , size , intracavitary growth , and location of the submucous myomas were compared with those revealed by direct inspection of the surgical specimens . Results Conventional transvaginal sonography for the diagnosis of submucous myomas had a sensitivity of 90 % and a specificity of 98 % ; the predictive values of abnormal and normal scans were 90 and 98 % , respectively . Transabdominal sonohysterography had sensitivity , specificity , and predictive values of 100 % , as did hysteroscopy . In all cases , the sonographic techniques measured tumor size more accurately than did hysteroscopy . The transabdominal sonohysterography measurements differed from direct evaluation by no more than 2 mm , and the hysteroscopic measurements were significantly different from those of the surgical specimens . The sonohysterographic evaluation of intrauterine growth was significantly more precise than that of the other techniques , differing from direct measurements by no more than 5–10 % . Conventional transvaginal sonography failed to localize three of 11 myomas ; hysteroscopy and transabdominal sonohysterography provided the exact location in all cases . Conclusion Transabdominal sonohysterography is the most accurate technique for detecting submucous myomas and evaluating their size , intracavitary growth , and location BACKGROUND There is no consensus as to whether uterine fibroids have any adverse effects on the outcomes of assisted reproduction treatment . This prospect i ve study compared implantation/pregnancy rates of women with and without fibroids undergoing IVF-embryo transfer and measured uterine blood flow indices of the fibroid group . METHODS Patients who had fibroids that , during transvaginal scanning , were found to be not distorting the endometrial lining were placed in the fibroid group , while patients with normal uteri were controls . Those with previous myomectomy or pedunculated subserosal fibroids only were excluded . All received a st and ard ovarian stimulation regimen . Doppler ultrasound examinations of uterine arteries were carried out in the fibroid group prior to oocyte retrieval . RESULTS Similar implantation/pregnancy rates , multiple pregnancy rates and pregnancy outcomes were noted in both groups . In the fibroid group , significantly lower pulsatility index ( PI ) and resistance index ( RI ) of the right uterine artery and the average of right and left uterine arteries were found in those failing to conceive than in those patients who subsequently conceived ( P < 0.001 ) . CONCLUSION The presence of fibroids not distorting the endometrial lining does not adversely affect implantation and pregnancy rates during IVF-embryo transfer . Significantly lower uterine artery PI and RI were found in non-pregnant women with fibroids than in their pregnant counterparts BACKGROUND Although uterine fibroids occur in 30 % of women and are associated with a degree of subfertility , the effect of intramural fibroids on the outcome of IVF or ICSI treatment has not been prospect ively studied . METHODS Data were prospect ively collected on 434 women undergoing IVF/ICSI in the assisted conception unit of an inner London teaching hospital . Patients were assessed for the presence of fibroids by transvaginal ultrasound and hysterosonography or hysteroscopy where appropriate . RESULTS During the study period , 112 women with ( study ) , and 322 women without ( controls ) , intramural fibroids were treated . Patients were similar regarding the cause and duration of their infertility , number of previous treatments , and basal serum FSH concentration . Women in the study group were on average 2 years older ( 36.4 versus 34.6 years ; P < 0.01 ) . There was no significant difference in the duration of ovarian stimulation or gonadotrophin requirement , number of follicles developed , oocytes collected , embryos available for transfer or replaced . When analysing only women with intramural fibroids of < or = 5 cm in size ( n = 106 ) pregnancy , implantation and ongoing pregnancy rates were significantly reduced : 23.3 , 11.9 and 15.1 respectively compared with 34.1 , 20.2 and 28.3 % in the control group ( P = 0.016 , P = 0.018 and P = 0.003 ) . The mean size of the largest fibroids was 2.3 cm ( 90 % range 2.1 - 2.5 cm ) . Logistic regression analysis demonstrated that the presence of intramural fibroids was one of the significant variables affecting the chance of an ongoing pregnancy , even after controlling for the number of embryos available for replacement and increasing age , particularly age > or = 40 years , odds ratio 0.46 ( CI 0.24 - 0.88 ; P = 0.019 ) . CONCLUSION This study demonstrated that an intramural fibroid halves the chances of an ongoing pregnancy following assisted conception This prospect i ve , controlled study was performed in order to evaluate whether the location of uterine fibroids may influence reproductive function in women and whether removal of the fibroid prior to conception may improve pregnancy rate and pregnancy maintenance . We examined 181 women affected by uterine fibroids who had been trying to conceive for at least 1 year without success . The main outcome measures were the pregnancy rate and the miscarriage rate . Among the patients who underwent myomectomy , the pregnancy rates obtained were 43.3 % in cases of submucosal , 56.5 % in cases of intramural , 40.0 % in cases of submucosal – intramural and 35.5 % in cases of intramural – subserosal uterine fibroids , respectively . Among the patients who did not undergo surgical treatment , the pregnancy rates obtained were 27.2 % in women with submucosal , 41.0 % in women with intramural , 15.0 % in women with submucosal – intramural and 21.43 % in women with intramural – subserosal uterine fibroids , respectively . Although the results were not statistically significant in the group of women with intramural and intramural – subserosal fibroids , this study confirms the important role of the position of the uterine fibroid in infertility as well as the importance of fibroids removal before the achievement of a pregnancy , to improve both the chances of fertilization and pregnancy maintenance OBJECTIVE To evaluate the role of sonohysterography for screening of the uterine cavity in patients with recurrent pregnancy loss . DESIGN Prospect i ve evaluation of sonohysterography , including comparison with available hysterosalpingography and hysteroscopy . SETTING University referral center . PATIENT(S ) Thirty-four reproductive-aged women with at least two consecutive pregnancy losses . INTERVENTION(S ) Sonohysterography was performed on all patients , using saline instilled through an endocervically placed balloon catheter with concurrent vaginal sonography . RESULT ( S ) Seventeen of 34 sonohysterograms ( 50.0 % ) demonstrated intrauterine abnormalities . Eighteen of 34 cases have undergone hysteroscopy or , in 1 case , laparoscopy . All confirmed the positive or negative sonohysterographic finding , result ing in a sensitivity and specificity of 100 % . Additionally , 100 % ( 12/12 ) of the defects were diagnosed accurately at sonohysterography when confirmed by surgery . Twenty-seven of 34 patients also had a hysterosalpingogram that demonstrated a 90.0 % sensitivity and 20.0 % specificity based on hysteroscopic findings , yet only 5 of 11 ( 45.5 % ) defects were diagnosed accurately at hysterosalpingography when compared with surgery . CONCLUSION ( S ) Sonohysterography is a highly sensitive , specific , and accurate screening tool for the evaluation of uterine cavitary defects associated with recurrent pregnancy loss and offers several advantages over hysterosalpingography The goal of this study was to assess the risk of adhesions after laparoscopic myomectomy . To this end our enquiry was based on observations with a prospect i ve collection of data . Between October 26 , 1990 and October 1 , 1996 , 45 patients underwent a second look after laparoscopic myomectomy . Seventy-two myomectomy sites were checked . The overall rate of postoperative adhesion was 35.6 % per patient . The rate of adhesions per myomectomy site was 16.7 % . The factors which influenced the occurrence of an adhesion on the myomectomy site were posterior location of the myoma and the existence of sutures . The rate of adhesions on the adnexa after laparoscopic myomectomy was 24.4 % . The factors which influenced the occurrence of adnexal adhesions were another surgical procedure carried out at the same time , the existence of adhesions prior to the operation and posterior location of the myoma . The rate of adhesions after laparoscopic myomectomy is low and the adhesions rarely involved the adnexa . We recommend that a second-look laparoscopy be carried out systematic ally after laparoscopic myomectomy in patients desiring pregnancy Output:

RESULT ( S ) Women with subserosal fibroids had no differences in their fertility outcomes compared with infertile controls with no myomas , and myomectomy did not change these outcomes compared with women with fibroids in situ . Women with intramural fibroids appear to have decreased fertility and increased pregnancy loss compared with women without such tumors , but study quality is poor . Myomectomy does not significantly increase the clinical pregnancy and live birth rates , but the data are scarce . Fibroids with a submucosal component led to decreased clinical pregnancy and implantation rates compared with infertile control subjects . Removal of submucous myomas appears likely to improve fertility . CONCLUSION ( S ) Fertility outcomes are decreased in women with submucosal fibroids , and removal seems to confer benefit . Subserosal fibroids do not affect fertility outcomes , and removal does not confer benefit . Intramural fibroids appear to decrease fertility , but the results of therapy are unclear .

MS214102

***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 project aim ed to evaluate the impact of a home visiting programme that targeted families where the child , for environmental reasons , was at great risk of poor health and developmental outcomes . METHODOLOGY Women in the immediate postpartum period were recruited to a r and omized double-blind controlled trial on the basis of self-reported vulnerability factors and were r and omly assigned to receive either a structured programme of nurse home visiting , supported by a social worker and paediatrician ( n = 90 ) , or assigned to a comparison group receiving st and ard community child health services ( n = 91 ) . Parenting stress and maternal depression were measured at enrollment and at 6 weeks . Preventive health behaviour , service satisfaction and home environment outcomes were tested at 6 weeks , as were child health outcomes . RESULTS At six weeks , women receiving the home-based programme had significant reductions in postnatal depression screening scores as well as improvements in their experience of the parental role and improvement in the ability to maintain their own identity . Maternal-infant interactions were more likely to be positive , with significantly higher ( better ) scores in aspects of the home environment related to optimal development in children , particularly maternal-infant secure attachment . Intervention group mothers were significantly more satisfied with the community child health service . CONCLUSIONS This form of intervention for families is effective in promoting secure maternal-infant attachment , preventing maternal mood disorder and is welcomed by the families receiving it . These findings may predict long-term benefits for the healthy development of children otherwise at risk of a range of poor health and development outcomes BACKGROUND Women who have suffered one episode of postpartum-onset major depression ( PPMD ) comprise a high-risk group for subsequent episodes . We conducted a double-blind , r and omized clinical trial to test the efficacy of nortriptyline in the prevention of recurrent PPMD . METHOD Nondepressed women who had at least one past episode of PPMD ( Research Diagnostic Criteria ) were recruited during pregnancy . Subjects were r and omly assigned to nortriptyline or placebo . Treatment began immediately postpartum . Each subject was assessed for 20 sequential weeks with the Hamilton Rating Scale for Depression and Research Diagnostic Criteria for recurrence of major depression . RESULTS No difference was found in the rate of recurrence in women treated with nortriptyline compared with those treated with placebo . Of 26 subjects who took nortriptyline preventively , 6 ( 0.23 , 95 % exact confidence interval [ CI ] = 0.09 to 0.44 ) suffered recurrences . Of 25 subjects who took placebo , 6 ( 0.24 , 95 % exact CI = 0.09 to 0.45 ) suffered recurrence ( Fisher exact p = 1.00 ) . CONCLUSION Nortriptyline did not confer additional preventive efficacy beyond that of placebo . The rate of recurrence of PPMD ( one fourth of women ) was unacceptably high OBJECTIVE Postpartum depression affects between 10 and 15 percent of new mothers . These mothers are apprehensive about recurrence after later births . This study tested the efficacy of antidepressant medication administered during the postpartum period to prevent a recurrence of postpartum depression among women who had suffered a previous episode . METHODS An open clinical trial was conducted at a university-based outpatient clinic treating pregnant and postpartum women with mood disorders . Study participants were 23 pregnant women who had at least one previous postpartum episode that fit DSM-III-R criteria for nonbipolar major depression without psychotic features . Postpartum monitoring for recurrence of depressive symptoms was compared with postpartum monitoring plus postbirth treatment with either the medication that had been effective for the previous episode or nortriptyline . The first dose was given within 24 hours of birth . The authors assessed recurrence of postpartum major depression by psychiatric examination and use of the Inventory to Diagnose Depression , a reliable self-report instrument . RESULTS A significantly greater proportion of the women who elected monitoring alone ( 62.5 percent ) suffered recurrence of major depression compared with the women who received monitoring plus medication ( 6.7 percent ) ( p = .0086 ) . CONCLUSIONS Prophylactic antidepressant treatment reduced the recurrence of postpartum major depression Abstract Objectives : To establish the relative cost effectiveness of postnatal support in the community in addition to the usual care provided by community midwives . Design : R and omised controlled trial with six month follow up . Setting : Recruitment in a university teaching hospital and care provided in women 's homes . Participants : 623 postnatal women allocated at r and om to intervention ( 311 ) or control ( 312 ) group . Intervention : Up to 10 home visits in the first postnatal month of up to three hours duration by a community postnatal support worker . Main outcome measure : General health status as measured by the SF-36 and risk of postnatal depression . Breast feeding rates , satisfaction with care , use of services , and personal costs . Results : At six weeks there was no significant improvement in health status among the women in the intervention group . At six weeks the mean total NHS costs were £ 635 for the intervention group and £ 456 for the control group ( P=0.001 ) . At six months figures were £ 815 and £ 639 ( P=0.001 ) . There were no differences between the groups in use of social services or personal costs . The women in the intervention group were very satisfied with the support worker visits . Conclusions : There was no health benefit of additional home visits by community postnatal support workers compared with traditional community midwifery visiting as measured by the SF-36 . There were no savings to the NHS over six months after the introduction of the community postnatal support worker service UNLABELLED Adverse childbirth experiences can evoke fear and overwhelming anxiety for some women and precipitate posttraumatic stress disorder . The objective of this study was to assess a midwife-led brief counseling intervention for postpartum women at risk of developing psychological trauma symptoms . METHOD Of 348 women screened for trauma symptoms , 103 met inclusion criteria and were r and omized into an intervention ( n = 50 ) or a control ( n = 53 ) group . The intervention group received face-to-face counseling within 72 hours of birth and again via telephone at 4 to 6 weeks postpartum . Main outcome measures were posttraumatic stress symptoms , depression , self-blame , and confidence about a future pregnancy . RESULTS At 3-month follow-up , intervention group women reported decreased trauma symptoms , low relative risk of depression , low relative risk of stress , and low feelings of self-blame . Confidence about a future pregnancy was higher for these women than for control group women . Three intervention group women compared with 9 control group women met the diagnostic criteria for posttraumatic stress disorder at 3 months postpartum , but this result was not statistically significant . DISCUSSION A high prevalence of postpartum depression and trauma symptoms occurred after childbirth . Although most women improved over time , the intervention markedly affected participants ' trajectory toward recovery compared with women who did not receive counseling . CONCLUSIONS A brief , midwife-led counseling intervention for women who report a distressing birth experience was effective in reducing symptoms of trauma , depression , stress , and feelings of self-blame . The intervention is within the scope of midwifery practice , caused no harm to participants , was perceived as helpful , and enhanced women 's confidence about a future pregnancy BACKGROUND Social support theory and observational risk factor studies suggest that increased antenatal psychosocial support could prevent post-natal depression . We used empirical knowledge of risk and protective factors for post-natal depression not employed previously in order to develop and evaluate an antenatal preventive intervention . METHODS We conducted a pragmatic r and omized controlled trial in antenatal clinics . We screened 1300 primiparous women and 400 screened positive , 69 screen-positive women were untraceable or not eligible . Of 292 women who completed baseline assessment , 209 consented to r and omization , of these 190 provided outcome data 3 months post-natally . ' Preparing for Parenthood ' , a structured antenatal risk factor reducing intervention design ed to increase social support and problem-solving skills , was compared with routine antenatal care only . We compared the percentage depressed at 3 months after childbirth using the self-completion General Health Question naire Depression scale and Edinburgh Post-natal Depression Scale ( EPDS ) , and the Schedules for Clinical Assessment in Neuropsychiatry a systematic clinical interview . RESULTS Assignment to the intervention group did not significantly impact on post-natal depression ( odds ratio for GHQ-Depression 1.22 ( 95 % CI 0.63 - 2.39 ) , P = 0.55 ) or on risk factors for depression . Forty-five per cent of the intervention group women attended sufficient sessions to be likely to benefit from intervention if effective . Attenders benefited no more than non-attenders . CONCLUSIONS Prevention services targeting post-natal depression should not implement antenatal support programmes on these lines until further research has demonstrated the feasibility and effectiveness of such methods . The development of novel , low cost interventions effective in reducing risk factors should be completed before further trial evaluation OBJECTIVES To investigate the effectiveness of a psychosocial intervention for the prevention of postnatal depression . DESIGN A controlled trial . METHOD Women expecting their first or second child and design ated as ' more vulnerable ' by the Leverton Question naire ( LQ ) or Crown Crisp Experiential Index ( CCEI ) were allocated to a preventive intervention ( N = 47 ) or control group ( N = 52 ) by expected date of delivery to provide groups expecting their babies around the same time . Women were assessed at 3 months postnatal . An additional group of women design ated as ' less vulnerable ' ( N = 88 ) were assessed to confirm the validity of the LQ as a vulnerability measure . RESULTS Question naire measures of mood in first-time mothers invited to the Preparation for Parenthood groups revealed significantly more positive mood than in the group receiving routine care . The median Edinburgh Postnatal Depression Scale ( EPDS ) score for those invited was 3 , compared to 8 for those not invited ( p < .005 ) . The diagnosis of depression using the Present State Examination revealed differences for both groups , though it reached statistical significance only with the first-time mothers . Only 19 % of the ' more vulnerable ' invited first-time mothers were ' borderline ' or ' cases ' at any time in the first 3 months postnatally compared to 39 % of those not invited . The Surviving Parenthood groups for second-time mothers were not successful . CONCLUSION Some depressions following childbirth can be prevented by brief interventions that can be incorporated with existing systems of antenatal classes and postnatal support groups BACKGROUND A prospect i ve epidemiology study evaluated the role of specific social and psychological variables in the prediction of depressive symptomatology and disorders following childbirth in a community sample . Measures of social support used previously in clinical ly depressed population s facilitated further comparison . METHODS Nulliparous pregnant women ( N = 507 ) were interviewed during pregnancy with the Interview Measure of Social Relationships ( IMSR ) and a context ual assessment of pregnancy-related support and adversity and 427 were followed up at 3 months postpartum with the 30-item GHQ , including six depression items . To establish the clinical representativeness of the GHQ , high GHQ scorers and a r and om sub sample of low scorers were interviewed using the SCAN . Regression models were developed using the GHQ Depression scale ( GHQ-D ) , the IMSR and other risk factor data . RESULTS GHQ-D after childbirth was predicted by lack of perceived support from members of the woman 's primary group and lack of support in relation to the event becoming pregnant ; this held even after controlling for antenatal depression , neuroticism , family and personal psychiatric history and adversity . Informant-rated deficits in provision of social support also predicted later depression . The size of the primary social network group previously found to be related to depression in women , did not predict depressive symptom development . CONCLUSION Predictors of depressive symptom development differ from predictors of recovery from clinical depression in women . Interventions should be design ed to reduce specific deficits in social support observed in particular study population OBJECTIVE To test whether critical incident stress debriefing after childbirth reduces the incidence of postnatal psychological disorders . DESIGN R and omised single-blind controlled trial stratified for parity and delivery mode . SETTING Two large maternity hospitals in Perth . PARTICIPANTS 1745 women who delivered healthy term infants between April 1996 and December 1997 ( 875 allocated to intervention and 870 to control group ) . INTERVENTION An individual , st and ardised debriefing session based on the principles of critical incident stress debriefing carried out within 72 hours of delivery . MAIN OUTCOME MEASURES Diagnosis of stress disorders or depression in the 12 months postpartum , using structured psychological interview and criteria of the Diagnostic and statistical manual of mental disorders , 4th edition . RESULTS Follow-up information was available for 1730 women ( 99.1 % ) , 482 of whom underwent psychological interview . There were no significant differences between control and intervention groups in scores on Impact of Events or Edinburgh Postnatal Depression Scales at 2 , 6 or 12 months postpartum , or in proportions of women who met diagnostic criteria for a stress disorder ( intervention , 0.6 % v control , 0.8 % ; P = 0.58 ) or major or minor depression ( intervention , 17.8 % v control , 18.2 % ; relative risk [ 9 Output:

Diverse psychosocial or psychological interventions do not significantly reduce the number of women who develop postnatal depression . The most promising intervention is the provision of intensive , professionally based postpartum support

MS214103

***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: Prognosis studies are investigations of future events or the evaluation of associations between risk factors and health outcomes in population s of patients ( 1 ) . The results of such studies improve our underst and ing of the clinical course of a disease and assist clinicians in making informed decisions about how best to manage patients . Prognostic research also informs the design of intervention studies by helping define subgroups of patients who may benefit from a new treatment and by providing necessary information about the natural history of a disorder ( 2 ) . There has recently been a rapid increase in the use of systematic review methods to synthesize the evidence on research questions related to prognosis . It is essential that investigators conducting systematic review s thoroughly appraise the method ologic quality of included studies to be confident that a study 's design , conduct , analysis , and interpretation have adequately reduced the opportunity for bias ( 3 , 4 ) . Caution is warranted , however , because inclusion of method ologically weak studies can threaten the internal validity of a systematic review ( 4 ) . This follows abundant empirical evidence that inadequate attention to biases can cause invalid results and inferences ( 5 - 9 ) . However , there is limited consensus on how to appraise the quality of prognosis studies ( 1 ) . A useful framework to assess bias in such studies follows the basic principles of epidemiologic research ( 10 , 11 ) . We focus on 6 areas of potential bias : study participation , study attrition , prognostic factor measurement , confounding measurement and account , outcome measurement , and analysis . The main objectives of our review of review s are to describe methods used to assess the quality of prognosis studies and to describe how well current practice s assess potential biases . Our secondary objective is to develop recommendations to guide future quality appraisal , both within single studies of prognostic factors and within systematic review s of the evidence . We hope this work facilitates future discussion and research on biases in prognosis studies and systematic review s. Methods Literature Search and Study Selection We identified systematic review s of prognosis studies by search ing MEDLINE ( 1966 to October 2005 ) using the search strategy recommended by McKibbon and colleagues ( 12 ) . This strategy combines broad search terms for systematic review s ( systematic review .mp ; meta- analysis .mp ) and a sensitive search strategy for prognosis studies ( cohort , incidence , mortality , follow-up studies , prognos * , predict * , or course ) . We also search ed the reference lists of included review s and method ologic papers to identify other relevant publications . We restricted our search to English- language publications . One review er conducted the search and selected the studies . Systematic review s , defined as review s of published studies with a comprehensive search and systematic selection , were included if they assessed the method ologic quality of the included studies by using 1 or more explicit criteria . We excluded studies if they were meta-analyses of independent patient data only , if their primary goal was to investigate the effectiveness of an intervention or specific diagnostic or screening tests , or if they included studies that were not done on humans . Data Extraction and Synthesis Individual items included in the quality assessment of the systematic review s were recorded as they were reported in the publication ( that is , the information that would be available to readers and future review ers ) . We review ed journal Web sites and contacted the authors of the systematic review s for additional information when authors made such an offer in their original papers . When review s assessed different study design s by using different sets of quality items , we extracted only those items used to assess cohort studies . We constructed a comprehensive list of distinct items that the review s used to assess the quality of their included studies . The full text of each review was screened . All items used by the review authors to assess the quality of studies were extracted into a computerized spreadsheet by 1 review er . Two experienced review ers , a clinical epidemiologist and an epidemiologist , independently synthesized the quality items extracted from the prognosis review s to determine how well the systematic review s assessed potential biases . We did this in 3 steps : 1 ) identified distinct concepts or domains addressed by the quality items ; 2 ) grouped each extracted quality item into the appropriate domain or domains ; and 3 ) identified the domains necessary to assess potential biases in prognosis studies . We then used this information to assess how well the review s ' quality assessment included items from the domains necessary to assess potential biases . After completing each of the first 3 steps , the review ers met to attempt to reach a consensus . The consensus process involved each review er presenting his or her observations and results , followed by discussion and debate . A third review er was available in cases of persistent disagreement or uncertainty . In the first step , all domains addressed by the quality items were identified . The first review er iteratively and progressively defined the domains as items were extracted from the included review s. The second review er defined domains from a r and om list of all extracted quality items . Limited guidance was provided to the review ers so that their assessment s and definitions of domains would be independent . The review ers agreed on a final set of domains that adequately and completely defined all of the extracted items . In the second step , review ers independently grouped each extracted item into the appropriate domains . Review ers considered each extracted item by asking , What is each particular quality item addressing ? or What are the review 's authors getting at with the particular quality assessment item ? . Items were grouped into the domain or domains that best represented the concepts being addressed . For example , the extracted items at least 80 % of the group originally identified was located for follow-up and follow-up was sufficiently complete or does n't jeopardize validity were each independently classified by both review ers as assessing the domain completeness of follow-up adequate , whereas the extracted item quantification and description of all subjects lost to follow-up was classified as assessing the domain completeness of follow-up described . In the third step , we identified the domains necessary to assess potential biases . Each review er considered the ability of the identified domains to adequately address , at least in part , 1 of the following 6 potential biases : 1 ) study participation , 2 ) study attrition , 3 ) prognostic factor measurement , 4 ) confounding measurement and account , 5 ) outcome measurement , and 6 ) analysis . Domains were considered to adequately address part of the framework if information garnered from that domain would inform the assessment of potential bias . For example , both review ers judged that the identified domain study population represents source population or population of interest assessed potential bias in a prognosis study , whereas the domain research question definition did not , although the latter is an important consideration in assessing the inclusion of studies in a systematic review . Finally , on the basis of our previous ratings , we looked at whether each review included items from the domains necessary to assess the 6 potential biases . We calculated the frequency of systematic review s by assessing each potential bias and the number of review s that adequately assessed bias overall . From this systematic synthesis , we developed recommendations for improving quality appraisal in future systematic review s of prognosis studies . We used Microsoft Access and Excel 2002 ( Microsoft Corp. , Redmond , Washington ) for data management and SAS for Windows , version 9.1 ( SAS Institute , Inc. , Cary , North Carolina ) for descriptive statistics . Role of the Funding Sources The funding sources , the Canadian Institutes of Health Research , the Canadian Chiropractic Research Foundation , the Ontario Chiropractic Association , and the Ontario Ministry of Health and Long Term Care , did not have a role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . Results We identified 1384 potentially relevant articles . Figure 1 shows a flow chart of studies that were included and excluded . Figure 2 shows the number of review s identified by year of publication . We excluded 131 systematic review s of prognosis studies that did not seem to include any quality assessment of the included studies ; this represented 44 % of prognosis review s. We included 163 review s of prognosis studies in our analysis ( 13 - 175 ) . The most common topics were cancer ( 15 % ) , musculoskeletal disorders and rheumatology ( 13 % ) , cardiovascular ( 10 % ) , neurology ( 10 % ) , and obstetrics ( 10 % ) . Other review s included a wide range of health and health care topics . Sixty-three percent of the review s investigated the association between a specific prognostic factor and a particular outcome ; the remainder investigated multiple prognostic factors or models . The number of primary studies included in each systematic review ranged from 3 to 167 ( median , 18 [ interquartile range , 12 to 31 ] ) . A complete description of the included review s is available from the authors on request . Figure 1 . Flow diagram of inclusion and exclusion criteria of systematic review s. Figure 2 . Number of systematic review s of prognosis studies identified over time . Quality Items One hundred fifty-three review s provided adequate detail to allow extraction of quality items . Eight hundred eighty-two distinct quality items were extracted from the review s. Most review s developed their own set of quality items , with only a few applying criteria from previous review s. Most quality items The survival of diffuse large B-cell lymphoma patients varies considerably , reflecting the molecular diversity of tumors . In view of the controversy whether cytologic features , immunohistochemical markers or gene expression signatures may capture this molecular diversity , we investigated which features provide prognostic information in a prospect i ve trial in the R-CHOP treatment era . Within the cohort of DLBCLs patients treated in the RICOVER-60 trial of the German High- Grade Lymphoma Study Group ( DSHNHL ) , we tested the prognostic impact of IB morphology in 949 patients . The expression of immunohistochemical markers CD5 , CD10 , BCL2 , BCL6 , human leukocyte antigen (HLA)-DR , interferon regulatory factor-4/multiple myeloma-1 ( IRF4/MUM1 ) , and Ki-67 was assessed in 506 patients . Expression of the immunohistochemical markers tested was of modest , if any , prognostic relevance . Moreover , the Hans algorithm using the expression patterns of CD10 , BCL6 , and interferon regulatory factor-4/multiple myeloma-1 failed to show prognostic significance in the entire cohort as well as in patient subgroups . IB morphology , however , emerged as a robust , significantly adverse prognostic factor in multivariate analysis , and its diagnosis showed a good reproducibility among expert hematopathologists . We conclude , therefore , that IB morphology in DLBCL is likely to capture some of the adverse molecular alterations that are currently not detectable in a routine diagnostic setting , and that its recognition has significant prognostic power BACKGROUND Dose intensification with a combination of cyclophosphamide , doxorubicin , vincristine , and prednisolone ( CHOP ) every 2 weeks improves outcomes in patients older than 60 years with diffuse large B-cell lymphoma compared with CHOP every 3 weeks . We investigated whether this survival benefit from dose intensification persists in the presence of rituximab ( R-CHOP ) in all age groups . METHODS Patients ( aged ≥18 years ) with previously untreated bulky stage IA to stage IV diffuse large B-cell lymphoma in 119 centres in the UK were r and omly assigned central ly in a one-to-one ratio , using minimisation , to receive six cycles of R-CHOP every 14 days plus two cycles of rituximab ( R-CHOP-14 ) or eight cycles of R-CHOP every 21 days ( R-CHOP-21 ) . R-CHOP-21 was intravenous cyclophosphamide 750 mg/m(2 ) , doxorubicin 50 mg/m(2 ) , vincristine 1·4 mg/m(2 ) ( maximum dose 2 mg ) , and rituximab 375 mg/m(2 ) on day 1 , and oral prednisolone 40 mg/m(2 ) on days 1 - 5 , administered every 21 days for a total of eight cycles . R-CHOP-14 was intravenous cyclophosphamide 750 mg/m(2 ) , doxorubicin 50 mg/m(2 ) , vincristine 2 mg , rituximab 375 mg/m(2 ) on day 1 , and oral prednisolone 100 mg on days 1 - 5 , administered every 14 days for six cycles , followed by two further infusions of rituximab 375 mg/m(2 ) on day 1 every 14 days . The trial was not masked . The primary outcome was overall survival ( OS ) . This study is registered , number IS RCT N 16017947 . FINDINGS 1080 patients were assigned to R-CHOP-21 ( n=540 ) and R-CHOP-14 ( n=540 ) . With a median follow-up of 46 months ( IQR 35 - 57 ) , 2-year OS was 82·7 % ( 79·5 - 85·9 ) in the R-CHOP-14 group and 80·8 % ( 77·5 - 84·2 ) in the R-CHOP-21 ( st and ard ) group ( hazard ratio 0·90 , 95 % CI 0·70 - 1·15 ; p=0·3763 ) . No significant improvement was noted in 2-year progression-free survival ( R-CHOP-14 75·4 % , 71·8 - 79·1 , and R-CHOP-21 74·8 % , 71·0 - 78·4 ; 0·94 , 0·76 - 1·17 ; p=0·5907 ) . High international prognostic index , poor-prognosis molecular characteristics , and cell of origin were not predictive for benefit from either schedule . Grade 3 or 4 neutropenia was higher in the R-CHOP-21 group ( 318 [ 60 % ] of 534 vs 167 [ 31 % ] of 534 ) , with no prophylactic use of recombinant human granulocyte-colony stimulating factor m and ated in this group , Output:

Immunohistochemistry-determined cell-of-origin , and BCL2 and BCL6 translocation status added no additional prognostic value . Half of the studies on gene expression profiling-determined cell-of-origin and MYC translocation status found that germinal center B-cell – like ( GCB ) and no translocation were associated with better overall survival ( OS ) whereas the remaining studies found no effect of these covariates .

MS214104

***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 New ways of improving the efficacy of nicotine therapy need to be explored . We tested whether starting nicotine polacrilex gum treatment 4 weeks before the quit date improved smoking abstinence rates compared with starting treatment on the quit date . METHODS An open r and omized trial of 314 daily smokers ( mean , 23.7 cigarettes/d ) enrolled through the Internet and by physicians in Switzerl and from November 2005 to January 2007 . In the precessation treatment group , participants received nicotine polacrilex gum ( 4 mg , unflavored ) by mail for 4 weeks before and 8 weeks after their target quit date , and they were instructed to decrease their cigarette consumption by half before quitting . In the usual care group , participants received the same nicotine gum for 8 weeks after their quit date and were instructed to quit abruptly . Instructions were limited to a booklet sent by mail and access to a smoking cessation Web site . Results are expressed as self-reported abstinence rates at the end of treatment and as biochemically verified smoking abstinence ( cotinine plus carbon monoxide ) after 12 months . RESULTS Eight weeks after the target quit date , self-reported 4-week abstinence rates were 41.6 % in the precessation treatment group and 44.4 % in the usual care group ( P = .61 ) . One year after the target quit date , biochemically verified 4-week smoking abstinence rates were 20.8 % in the precessation treatment group and 19.4 % in the usual care group ( P = .76 ) . CONCLUSION Starting nicotine gum treatment 4 weeks before the target quit date was no more effective than starting treatment on the quit date One hundred ten patients addicted to nicotine were subjected to either sudden or gradual withdrawal in the course of a smoking cessation programme . Eighty-two patients emerged from the treatment as non-smokers . In a follow-up after 1 year 70 % of these successful clients replied to an anonymous question naire . Concerning the relapse rate , no significant difference could be found between the two treatment groups , but patients who underwent slow withdrawal smoked significantly less when comparing their current consumption with that before the start of the therapy . Patients who underwent sudden stopping reached their original level of nicotine use again Two recommended quit methods in st and ard cessation programs involve either gradual reduction of smoking prior to complete abstinence ( " cut down " ) or abrupt abstinence from cigarettes ( " cold turkey " ) . This study examined the reported use , characteristics of users , and the impact of self-selected strategy choice on quitting success and relapse of adult smokers who reported quitting on their own . Data came from the first three waves of the International Tobacco Control Policy Evaluation 4-Country Survey ( ITC-4 ) . The ITC-4 is a r and om-digit-dialed telephone survey of a cohort of more than 8,000 adult smokers from the United Kingdom , the United States , Canada , and Australia , with a 75 % follow-up rate . The results indicated that 68.5 % of the smokers who had made a quit attempt between waves reported using the cold-turkey method . Of those who used the cold turkey method , 22 % and 27 % succeeded at Waves 2 and 3 , respectively , compared with the 12 % and 16 % , respectively , who used the cut-down method . Multivariate analyses revealed that cold-turkey users were more likely to be aged 25 - 39 years , male , from the United Kingdom , and smoking heavily , and had lower perceived dependence . Controlling for sociodemographic and known predictors of quitting including use of medications , we found that smokers who used the cold-turkey method to quit were almost twice as likely to abstain for a month or more in their attempt . Overall , we cautiously conclude that cold turkey should be the recommended strategy for smokers who want to quit on their own OBJECTIVE To evaluate the smoking cessation efficacy of nicotine patch therapy as an adjunct to low-intensity , primary care intervention . DESIGN R and omized , placebo-controlled , double-blind , multisite trial . SETTING S Twenty-one primary care sites in Nebraska . PATIENTS A total of 369 smokers of 20 or more cigarettes per day . INTERVENTION Two brief primary care visits for smoking intervention with 10 weeks of active or placebo-patch therapy . MAIN OUTCOME MEASURES Confirmed self-reported abstinence 3 , 6 , and 12 months after the quit day . RESULTS Compared with placebo control subjects , participants assigned nicotine patches had higher 3-month ( 23.4 % vs 11.4 % ; P < .01 ) and 6-month ( 18.5 % vs 10.3 % ; P < .05 ) abstinence rates . The 1-year abstinence rates for the active and placebo patch groups were 14.7 % and 8.7 % , respectively ( P = .07 ) . Of smokers aged 45 years and older , 9 ( 18.8 % ) of 48 using active patches compared with 0 of 31 using placebo patches achieved 12-month abstinence ( chi 2 = 6.56 ; P < .05 ) . Among those with high nicotine dependency scores ( Fagerstrom score > or = 7 ) , 1-year abstinence rates were significantly higher in the nicotine patch group ( 19.1 % ) compared with the placebo group ( 5.0 % ) ( chi 2 = 10.7 ; P = .001 ) . However , there was no significant difference in 1-year quit rates for participants with low Fagerstrom scores ( < 7 ) . CONCLUSIONS Nicotine patch therapy enhanced 6 month quit rates as an adjunct to brief primary care intervention . The highest quit rates were achieved by participants who specifically contacted the site to enroll in the study or to obtain a prescription for nicotine patches . Differences in participant selection factors may account , in part , for the lower smoking cessation rates associated with primary care intervention . Duration of counseling , patient age , and Fagerstrom scores may be important factors related to the long-term smoking cessation success of nicotine patch therapy Background The st and ard way to stop smoking is to stop abruptly on a quit day with no prior reduction in consumption of cigarettes . Many smokers feel that reduction is natural and if reduction programmes were offered , many more might take up treatment . Few trials of reduction versus abrupt cessation have been completed . Most are small , do not use pharmacotherapy , and do not meet the st and ards necessary to obtain a marketing authorisation for a pharmacotherapy . Design / Methods We will conduct a non-inferiority r and omised trial of rapid reduction versus st and ard abrupt cessation among smokers who want to stop smoking . In the reduction arm , participants will be advised to reduce smoking consumption by half in the first week and to 25 % of baseline in the second , leading up to a quit day at which participants will stop smoking completely . This will be assisted by nicotine patches and an acute form of nicotine replacement therapy . In the abrupt arm participants will use nicotine patches only , whilst smoking as normal , for two weeks prior to a quit day , at which they will also stop smoking completely . Smokers in either arm will have st and ard withdrawal orientated behavioural support programme with a combination of nicotine patches and acute nicotine replacement therapy post-cessation . Outcomes /Follow-upThe primary outcome of interest will be prolonged abstinence from smoking , with secondary trial outcomes of point prevalence , urges to smoke and withdrawal symptoms . Follow up will take place at 4 weeks , 8 weeks and 6 months post-quit day . Trial Registration Current Controlled Trials IS RCT The nicotinic antagonist mecamylamine was evaluated in a r and omized smoking cessation trial . Four groups of participants ( n = 20 per group ) received nicotine plus mecamylamine , nicotine alone , mecamylamine alone , or no drug for 4 weeks before cessation . After the quit-smoking date , all subjects received nicotine plus mecamylamine treatment for 6 weeks . Nicotine skin patches ( 21 mg/24 hr ) and mecamylamine capsules ( 2.5 - 5.0 mg twice per day ) were used . Precessation mecamylamine significantly prolonged the duration of continuous smoking abstinence ; abstinence rates at the end of treatment were 47.5 % with mecamylamine and 27.5 % without mecamylamine . Nicotine + mecamylamine reduced ad lib smoking , smoking satisfaction , and craving more than either drug alone . Moreover , the orthostatic decrease in blood pressure caused by mecamylamine was offset by nicotine . Mecamylamine before smoking cessation may be an effective adjunct to nicotine patch therapy The present study investigated whether treatment with the combination of denicotinized cigarettes and 21-mg nicotine patch for 2 weeks before a design ated quit date could lessen cravings for smoking , thereby helping smokers abstain from smoking . The study was a r and omized controlled clinical trial conducted at Roswell Park Cancer Institute , Buffalo , New York , in 2004 and 2005 . Patients included 98 adult heavy smokers ( using 20 or more cigarettes/day ) . Half of the subjects received 2 weeks of combination of denicotinized cigarettes ( Quest 3 ) and 21-mg nicotine patch for 2 weeks before the quit date . The remaining smokers were switched to light cigarettes ( Quest 1 ) during the 2 weeks before the quit date . After the quit date , all subjects received counseling for smoking cessation and were provided nicotine patches for up to 8 weeks after the quit date . Self-reported cravings for smoking , withdrawal symptoms , and smoking abstinence were measured at predetermined intervals using phone-based surveys and in clinical visits . The group that used denicotinized cigarettes and nicotine patch before quitting reported less frequent and less intense cravings for cigarettes in the 2 weeks before and after the design ated quit date . Self-reported withdrawal symptoms and quit rates did not differ significantly between the groups . The use of a denicotinized cigarette combined with the nicotine patch appears to lessen cravings to smoke in the immediate postcessation period . A larger , better-powered study is needed to test if this treatment combination has merit for increasing quit rates The study examined the occurrence of acute tobacco withdrawal symptoms among three methods of smoking cessation . Smokers were asked to smoke ad lib for 3 days and then r and omly assigned to one of three groups for the next 5 days : ( 1 ) total cigarette cessation ; ( 2 ) 50 % reduction of number of cigarettes ; or ( 3 ) reduction of nicotine yield of cigarettes . Of the 13 measures of tobacco withdrawal , six of the measures showed significant differences in severity of withdrawal symptoms between the total cessation group and partial reduction groups . There were no significant differences in severity of withdrawal between the two partial reduction groups This study compared the efficacy of 2 traditional methods of smoking cessation , gradual reduction and " cold turkey , " with a new approach involving variation in the intercigarette interval . One hundred twenty-eight participants quit smoking on a target date , after a 3-week period of ( a ) scheduled reduced smoking ( progressive increase in the intercigarette interval ) , ( b ) nonscheduled reduced smoking ( gradual reduction , no specific change in the intercigarette interval ) , ( c ) scheduled nonreduced smoking ( fixed intercigarette interval , no reductions in frequency ) , or ( c ) nonscheduled nonreduced smoking ( no change in intercigarette interval or smoking frequency ) . Participants also received cognitive-behavioral relapse prevention training . Abstinence at 1 year averaged 44 % , 18 % , 32 % , and 22 % for the 4 groups , respectively . Overall , the scheduled reduced group performed the best and the nonscheduled reduced group performed the worst . Both scheduled groups performed better than nonscheduled ones . Scheduled reduced smoking was associated with reduced tension , fatigue , urges to smoke , withdrawal symptoms , increased coping effort ( ratio of coping behavior to urges ) , and self-efficacy , suggesting an improved adaptation to nonsmoking and reduced vulnerability to relapse Two theoretical approaches to smoking cessation were compared . Participants were r and omly assigned either to ( a ) a traditional treatment program that used contingency contracting and that emphasized the necessity for absolute abstinence ( AA ) or to ( b ) a relapse-prevention ( RP ) treatment that focused on gradual acquisition of nonsmoking skills . It was hypothesized that participants in the RP treatment would be less successful initially but would have better maintenance skills and thus would relapse less during a 1-year follow-up period . Each program was evaluated in two formats : group-based treatment and self-help material s. Results indicated comparable 1-year abstinence rates for all treatments , although more participants dropped out of the self-help formats . Participants in the RP intervention were more likely to lapse sooner after quitting and were more likely to quit again during the 1-year maintenance period . Exploratory analyses of successful participants suggested that women were more successful in the RP program and that men had greater success with the AA approach Tobacco use is a major cause of cardiovascular , respiratory and oncological disease . Quitting smoking significantly benefits health , but for highly dependent smokers , unable to overcome their nicotine dependence , the concept of smoking reduction as a method of harm reduction is gaining ground . The University Hospital of Basle , Switzerl and , has run double-blind , placebo-controlled smoking cessation and smoking reduction studies : the CEASE trial Output:

We were unable to draw conclusions about the difference in adverse events between interventions , however recent studies suggest that pre-quit NRT does not increase adverse events . AUTHORS ' CONCLUSIONS Reducing cigarettes smoked before quit day and quitting abruptly , with no prior reduction , produced comparable quit rates , therefore patients can be given the choice to quit in either of these ways .

MS214105

***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 Large numbers of women who participate in cervical screening require follow-up for minor cytological abnormalities . Little is known about the psychological consequences of alternative management policies for these women . We compared , over 30-months , psychosocial outcomes of two policies : cytological surveillance ( repeat cervical cytology tests in primary care ) and a hospital-based colposcopy examination . Methods Women attending for a routine cytology test within the UK NHS Cervical Screening Programmes were eligible to participate . 3399 women , aged 20–59 years , with low- grade abnormal cytology , were r and omised to cytological surveillance ( six-monthly tests ; n = 1703 ) or initial colposcopy with biopsies and /or subsequent treatment based on colposcopic and histological findings ( n = 1696 ) . At 12 , 18 , 24 and 30-months post-recruitment , women completed the Hospital Anxiety and Depression Scale ( HADS ) . A subgroup ( n = 2354 ) completed the Impact of Event Scale ( IES ) six weeks after the colposcopy episode or first surveillance cytology test . Primary outcomes were percentages over the entire follow-up period of significant depression ( ≥8 ) and significant anxiety ( ≥11 ; “ 30-month percentages ” ) . Secondary outcomes were point prevalences of significant depression , significant anxiety and procedure-related distress ( ≥9 ) . Outcomes were compared between arms by calculating fully-adjusted odds ratios ( ORs ) for initial colposcopy versus cytological surveillance . Results There was no significant difference in 30-month percentages of significant depression ( OR = 0.99 , 95 % CI 0.80–1.21 ) or anxiety ( OR = 0.97 , 95 % CI 0.81–1.16 ) between arms . At the six-week assessment , anxiety and distress , but not depression , were significantly less common in the initial colposcopy arm ( anxiety : 7.9 % vs 13.4 % ; OR = 0.55 , 95 % CI 0.38–0.81 ; distress : 30.6 % vs 39.3 % , OR = 0.67 95 % CI 0.54–0.84 ) . Neither anxiety nor depression differed between arms at subsequent time-points . Conclusions There was no difference in the longer-term psychosocial impact of management policies based on cytological surveillance or initial colposcopy . Policy-makers , clinicians , and women themselves can be reassured that neither management policy has a significantly greater psychosocial cost . Trial Registration Controlled-Trials.com IS RCT N OBJECTIVE The success of cervical screening relies on women with abnormal cervical cytology attending for follow-up by colposcopy and related procedures . Failure to attend for colposcopy , however , is a common problem in many countries . The objective of this study was to identify factors associated with non-attendance at an initial colposcopy examination among women with low- grade abnormal cervical cytology . STUDY DESIGN A cohort study was conducted within one arm of a multi-centre population -based r and omised controlled trial nested within the UK NHS Cervical Screening Programmes . The trial recruited women aged 20 - 59 years with recent low- grade cervical cytology ; women r and omised to immediate referral for colposcopy were included in the current analysis ( n=2213 ) . At trial recruitment , women completed a socio-demographic and lifestyle question naire ; 1693 women in the colposcopy arm were also invited to complete a psychosocial question naire , including the Hospital Anxiety and Depression Scale . Women were sent up to two colposcopy appointments . A telephone number was provided to reschedule if necessary . Defaulters were defined as those who failed to attend after two appointments . Logistic regression methods were used to compute multivariate odds ratios ( OR ) to identify variables significantly associated with default . RESULTS 148 women defaulted ( 6.7 % , 95%CI 5.7 - 7.8 % ) . In multivariate analysis , risk of default was significantly raised in those not in paid employment ( OR=2.70 , 95%CI 1.64 - 4.43 ) and current smokers ( OR=1.62 , 95%CI 1.12 - 2.34 ) . Default risk deceased with increasing age and level of post-school education/training and was lower in women with children ( OR=0.59 , 95%CI 0.35 - 0.98 ) . Among the sub-group invited to complete psychosocial question naires , women who were not worried about having cervical cancer were significantly more likely to default ( multivariate OR=1.56 , 95%CI 1.04 - 2.35 ) . Anxiety and depression were not significantly associated with default . CONCLUSIONS Women at highest risk of default from colposcopy are younger , not in paid employment , smoke , lack post-school education , have not had children and are not worried about having cervical cancer . Findings such as these could inform the development of tools to predict the likelihood that an individual woman will default from follow-up . Interventions to minimise default also deserve consideration , but a better underst and ing of reasons for default is needed to inform intervention development OBJECTIVE To investigate the potential value of tree classifiers for the triage of high- grade squamous intraepithelial lesions . STUDY DESIGN The data set comprised 808 histologically confirmed cases having a complete range of the cytologic sample assessment s -- liquid-based cytology , reflex human papillomavirus ( HPV ) DNA test , E6/E7 HPV mRNA test , and p16 immunocytochemical examinations . Data include 488 histologically negative ( cervical intraepithelial neoplasia [ CIN ] 1 and below ) or clinical ly negative cases and 320 with histologic diagnosis of CIN 2 or worse . Cytologic diagnosis was made according to the criteria of the Bethesda System . Cases were classified in two groups according to histology : those with CIN 2 or worse and those with CIN 1 and below . Fifty percent were r and omly selected as a training set and the remaining were as a test set . RESULTS Application of tree classifier on the test set gave correct classification of 66.9 % for CIN 2 and above cases and 97.3 % for CIN 1 and below , producing overall accuracy of 91.5 % , outperforming cytologic diagnosis alone . CONCLUSION Application of tree classifiers , based on st and ard cytologic diagnosis and expression of studied biomarkers , produces improved classification results for cervical precancerous lesions and cancer diagnosis OBJECTIVE The detection of high- grade cervical intraepithelial neoplasia ( CIN ) amongst patients with low- grade cytology ( LSIL ) is challenging . This study evaluated the role of high-risk HPV ( HR-HPV ) DNA test and p16(INK4a ) immunostaining in identifying women with LSIL cytology at risk of harboring CIN2 or worse ( CIN2 + ) and the role of p16(INK4a ) in the triage of a population of HR-HPV positive LSIL . METHODS We conducted a prospect i ve study including women with LSIL cytology . Detection of HR-HPV was carried out by means of a polymerase chain reaction based assay . p16(INK4a ) immunostaining was performed using the Dako CINtec cytology kit . All patients had colposcopically directed punch biopsies or large loop excision of the transformation zone of the cervix . The endpoint was detection of a biopsy-confirmed CIN2 + . RESULTS A series of 126 women with LSIL cytology were included . HR-HPV test had sensitivity 75 % and specificity 64 % for an endpoint of CIN2 + . p16(INK4a ) had significantly higher specificity of 89 % ( p=0.0000 ) but low sensitivity of 42 % . The role of p16(INK4a ) immunostaining in the triage of LSIL positive for HR-HPV was also evaluated . p16(INK4a ) triage had 70 % positive predictive value ( PPV ) ; however , this was not significantly higher than the PPV ( 56 % ) of HR-HPV test alone ( p=0.4 ) . CONCLUSIONS The results indicate that HR-HPV or p16(INK4a ) can not be used as solitary markers for the assessment of LSIL . The addition of p16(INK4a ) immunostaining led to an increase in HR-HPV specificity ; however , the biomarker needs to be assessed further to establish its role as an adjunct test in the triage of LSIL Objectives To compare the effectiveness of punch biopsy and selective recall for treatment versus a policy of immediate treatment by large loop excision in the management of women with low grade abnormal cervical cytology referred for colposcopy . Design Multicentre individually r and omised controlled trial , nested within the NHS cervical screening programmes . Setting Grampian , Tayside , and Nottingham . Participants 1983 women , aged 20 - 59 , with cytology showing borderline nuclear abnormalities or mild dyskaryosis , October 1999-October 2002 . Interventions Immediate large loop excision or up to four targeted punch biopsies taken immediately with recall for treatment ( by large loop excision ) if these showed cervical intraepithelial neoplasia grade II or III or worse . Participants were followed for three years , concluding with an exit colposcopy . Main outcome measures Clinical end points : cumulative incidence of cervical intraepithelial neoplasia grade II or worse and grade III or worse at three years . Clinical ly significant anxiety and depression and self reported after effects assessed six weeks after colposcopy , biopsies , or large loop excision . Results 879 women ( 44 % ) had a normal transformation zone at colposcopy and had no further procedures at that time . Colposcopists were less likely to classify the transformation zone as abnormal when the allocation was large loop excision ( 603 ( 60 % ) in the biopsy and selective recall group ; 501 ( 51 % ) in the immediate large loop excision group ) . Of women r and omised to biopsy and recall , 157 ( 16 % ) required a second clinic visit for treatment . Specimens from almost 60 % ( n=296 ) of women who underwent immediate large loop excision showed no cervical intraepithelial neoplasia ( 31 % ; n=156 ) or showed cervical intraepithelial neoplasia grade I ( 28 % ; n=140 ) . The percentages of women diagnosed with grade II or worse up to and including the exit examination were 22 % ( n=216 ) in the biopsy and recall arm and 23 % ( n=228 ) in the immediate large loop excision arm . There was no significant difference between the arms in cumulative incidence of cervical intraepithelial neoplasia grade II or worse ( adjusted relative for risk large loop excision v biopsy 1.04 , 95 % confidence interval 0.86 to 1.25 ) or grade III or worse ( 1.03 , 0.79 to 1.34 ) . A greater proportion of disease was detected at initial investigation and less during follow-up and at exit in the immediate large loop excision arm , but time of detection did not differ significantly between arms . Levels of anxiety and depression and reported pain did not differ between arms . Higher proportions of women r and omised to large loop excision reported moderate or more severe bleeding and discharge . Conclusion A policy of targeted punch biopsies with subsequent treatment for cervical intraepithelial neoplasia grade II or III and cytological surveillance for grade I or less provides the best balance between benefits and harms for the management of women with low grade abnormal cytology referred for colposcopy . Immediate large loop excision results in overtreatment and more after effects and should not be recommended . Trial Registration IS RCT N 34841617 Objective It is well known that receipt of an initial abnormal cervical cytology test can trigger considerable anxiety among women . Less is known about the impact of follow-up by repeat cytology tests . We quantified prevalence , and identified predictors , of distress after repeat cytologic testing in women with a single low- grade test . Methods Within the framework of the TOMBOLA r and omized controlled trial of alternative managements , 844 women aged 20 to 59 years with a single routine cytology test showing borderline nuclear abnormalities ( BNA ; broadly equivalent to atypical squamous cells of undetermined significance ) were assigned to follow-up by repeat cytology in primary care ( the first test was due 6 months after the initial BNA result ) . Women completed sociodemographic and psychosocial question naires at recruitment and the Impact of Event Scale ( IES ) 6 weeks after their first follow-up cytology test . Factors associated with significant psychologic distress ( IES ≥ 9 ) were identified using logistic regression . Results The response rate was 74 % ( n = 621/844 ) . Of all the respondents , 39 % scored in the range for significant distress . Distress varied by follow-up cytology result : negative , 36 % ; BNA or mild dyskaryosis , 42 % ; other ( including high grade and inadequate ) , 55 % . After adjusting for the cytology result , risk of distress was significantly raised in women who had significant anxiety at recruitment , reported experiencing pain after the follow-up cyt Output:

Based on low- or moderate- quality evidence using the GRADE approach and generally low risk of bias , the detection rate of CIN2 + or CIN3 + after two years does not appear to differ between immediate colposcopy and cytological surveillance in the absence of HPV testing , although women may default from follow-up . Immediate colposcopy probably leads to earlier detection of high- grade lesions , but also detects more clinical ly insignificant low- grade lesions .

MS214106

***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 purpose of this study was to assess the effect of 8-weeks ingestion of a commercialized joint pain dietary supplement ( InstaflexTM Joint Support , Direct Digital , Charlotte , NC ) compared to placebo on joint pain , stiffness , and function in adults with self-reported joint pain . InstaflexTM is a joint pain supplement containing glucosamine sulfate , methylsufonlylmethane ( MSM ) , white willow bark extract ( 15 % salicin ) , ginger root concentrate , boswella serrata extract ( 65 % boswellic acid ) , turmeric root extract , cayenne , and hyaluronic acid . Methods Subjects included 100 men and women , ages 50 - 75 years , with a history ( > 3 months ) of joint pain , and were r and omized to Instaflex ™ or placebo ( 3 colored gel capsules per day for 8 weeks , double-blind administration ) . Subjects agreed to avoid the use of non-steroidal anti-inflammatory drugs ( NSAID ) and all other medications and supplements targeted for joint pain . Primary outcome measures were obtained pre- and post- study and included joint pain severity , stiffness , and function ( Western Ontario and McMaster Universities [ WOMAC ] ) , and secondary outcome measures included health-related quality of life ( Short Form 36 or SF-36 ) , systemic inflammation ( serum C-reactive protein and 9 plasma cytokines ) , and physical function ( 6-minute walk test ) . Joint pain symptom severity was assessed bi-weekly using a 12-point Likert visual scale ( 12-VS ) . Results Joint pain severity was significantly reduced in Instaflex ™ compared to placebo ( 8-week WOMAC , ↓37 % versus ↓16 % , respectively , interaction effect P = 0.025 ) , with group differences using the 12-VS emerging by week 4 of the study ( interaction effect , P = 0.0125 ) . Improvements in ability to perform daily activities and stiffness scores in Instaflex ™ compared to placebo were most evident for the 74 % of subjects reporting knee pain ( 8-week WOMAC function score , ↓39 % versus ↓14 % , respectively , interaction effect P = 0.027 ; stiffness score , ↓30 % versus ↓12 % , respectively , interaction effect P = 0.081 ) . Patterns of change in SF-36 , systemic inflammation biomarkers , and the 6-minute walk test did not differ significantly between groups during the 8-week study Conclusions Results from this r and omized , double blind , placebo-controlled community trial support the use of the Instaflex ™ dietary supplement in alleviating joint pain severity in middle-aged and older adults , with mitigation of difficulty performing daily activities most apparent in subjects with knee pain . Trial registration Clinical Trials.gov Identifier : Background The purpose of this study was to determine whether sedentary obese women with knee OA initiating an exercise and weight loss program may experience more beneficial changes in body composition , functional capacity , and /or markers of health following a higher protein diet compared to a higher carbohydrate diet with or without GCM supplementation . Methods Thirty sedentary women ( 54 ± 9 yrs , 163 ± 6 cm , 88.6 ± 13 kg , 46.1 ± 3 % fat , 33.3 ± 5 kg/m2 ) with clinical ly diagnosed knee OA participated in a 14-week exercise and weight loss program . Participants followed an isoenergenic low fat higher carbohydrate ( HC ) or higher protein ( HP ) diet while participating in a supervised 30-minute circuit resistance-training program three times per week for 14-weeks . In a r and omized and double blind manner , participants ingested supplements containing 1,500 mg/d of glucosamine ( as d-glucosamine HCL ) , 1,200 mg/d of chondroitin sulfate ( from chondroitin sulfate sodium ) , and 900 mg/d of methylsulfonylmethane or a placebo . At 0 , 10 , and 14-weeks , participants completed a battery of assessment s. Data were analyzed by MANOVA with repeated measures . Results Participants in both groups experienced significant reductions in body mass ( -2.4 ± 3 % ) , fat mass ( -6.0 ± 6 % ) , and body fat ( -3.5 ± 4 % ) with no significant changes in fat free mass or resting energy expenditure . Perception of knee pain ( -49 ± 39 % ) and knee stiffness ( -42 ± 37 % ) was decreased while maximal strength ( 12 % ) , muscular endurance ( 20 % ) , balance indices ( 7 % to 20 % ) , lipid levels (-8 % to -12 % ) , homeostasis model assessment for estimating insulin resistance ( -17 % ) , leptin ( -30 % ) , and measures of physical functioning ( 59 % ) , vitality ( 120 % ) , and social function ( 66 % ) were improved in both groups with no differences among groups . Functional aerobic capacity was increased to a greater degree for those in the HP and GCM groups while there were some trends suggesting that supplementation affected perceptions of knee pain ( p < 0.08 ) . Conclusions Circuit style resistance-training and weight loss improved functional capacity in women with knee OA . The type of diet and dietary supplementation of GCM provided marginal additive benefits .Trial Registration Clinical Trials.gov : The aim of this study was to investigate the effects of focused low-intensity pulsed ultrasound ( FLIPUS ) therapy on the functional and health status of patients with knee osteoarthritis ( KOA ) . A total of 106 subjects with bilateral KOA were r and omized sequentially into two groups . Group I received FLIPUS + diclofenac sodium , and group II received sham FLIPUS + diclofenac sodium . The therapeutic effects of the interventions were evaluated by measuring changes in VAS pain , the WOMAC scores , and the LI scores after 10 days of treatment as well as changes in LI and VAS at follow-up , 4 and 12 weeks later . In addition , changes in the range of motion , ambulation speed , and the SF-36 in each group were recorded after 10 days of treatment . Compared with those in group II , patients in group Ishowed significant improvements in VAS , WOMAC , LI , ambulation speed , and most items in the SF-36 after 10 days of treatment . In addition , patients in group I showed significant improvements in LI and VAS at follow-up . There were no FLIPUS-related adverse events during and after the interventions . In conclusion , FLIPUS is a safe and effective treatment modality for relieving pain and improving the functions and quality of life of patients with KOA Objectives : To estimate the effects of low level laser therapy in combination with a programme of exercises on pain , functionality , range of motion , muscular strength and quality of life in patients with osteoarthritis of the knee . Design : A r and omized double-blind placebo-controlled trial with sequential allocation of patients to different treatment groups . Setting : Special Rehabilitation Services . Subjects : Forty participants with knee osteoarthritis , 2–4 osteoarthritis degree , aged between 50 and 75 years and both genders . Intervention : Participants were r and omized into one of two groups : the laser group ( low level laser therapy dose of 3 J and exercises ) or placebo group ( placebo laser and exercises ) . Main measures : Pain was assessed using a visual analogue scale ( VAS ) , functionality using the Lequesne question naire , range of motion with a universal goniometer , muscular strength using a dynamometer , and activity using the Western Ontario and McMaster Universities Osteoarthritis ( WOMAC ) question naire at three time points : ( T1 ) baseline , ( T2 ) after the end of laser therapy ( three weeks ) and ( T3 ) the end of the exercises ( 11 weeks ) . Results : When comparing groups , significant differences in the activity were also found ( P = 0.03 ) . No other significant differences ( P > 0.05 ) were observed in other variables . In intragroup analysis , participants in the laser group had significant improvement , relative to baseline , on pain ( P = 0.001 ) , range of motion ( P = 0.01 ) , functionality ( P = 0.001 ) and activity ( P < 0.001 ) . No significant improvement was seen in the placebo group . Conclusion : Our findings suggest that low level laser therapy when associated with exercises is effective in yielding pain relief , function and activity on patients with osteoarthritis of the knees Background Pharmacological treatment for osteoarthritis ( OA ) can be divided into two groups : symptom-modifying drugs and disease-modifying drugs . Symptom-modifying drugs are currently the prescription of choice for patients with OA , as disease-modifying drugs are not yet available in usual care . However , there has recently been a lot of debate about glucosamine sulphate ( GS ) , a biological agent that is thought to have both symptom-modifying and disease-modifying properties . This assumption has yet to be proved . The objective of this article is to present the design of a blind r and omised clinical trial that examines the long-term symptom-modifying and disease-modifying effectiveness of GS in patients with hip OA . This trial is ongoing and will finish in March 2006 . Methods / design Patients with hip OA meeting the ACR- criteria are r and omly allocated to either 1500 mg of oral GS or placebo for the duration of two years . The primary outcome measures , which are joint space narrowing ( JSN ) , and change in the pain and function score of the Western Ontario McMaster Universities Osteoarthritis index ( WOMAC ) , are determined at baseline and after two years of follow-up during the final assessment . Intermediate measures at three-month intervals throughout the trial are used to study secondary outcome measures . Secondary outcome measures are changes in WOMAC stiffness score , quality of life , medical consumption , side effects and differences in biomarker CTX-II The efficacy and safety of a once-daily extended-release formulation of tramadol hydrochloride ( tramadol ER ) was evaluated in patients with moderate to severe chronic pain of osteoarthritis ( OA ) . This was a r and omized , double-blind , placebo-controlled , parallel-group , 12-week study . Eligible patients with radiographically confirmed OA of the knee meeting the American College of Rheumatology diagnostic criteria , defined by knee pain and presence of osteophytes , plus at least age > 50 years , morning stiffness < 30 minutes in duration , and /or crepitus , entered a 2 - 7 day washout period during which all analgesics were discontinued . When pain at the index knee joint reached > or = 40 mm ( 0 - 100 mm VAS ) , patients were r and omized to tramadol ER or placebo . Tramadol ER was initiated at 100 mg QD and increased to 200 mg QD by the end of 1 week of treatment . After the first week , further increases to tramadol ER 300 mg or 400 mg QD were allowed . Outcome measures included Arthritis Pain Intensity Visual Analogue Scale ( VAS ) , Western Ontario and McMaster Universities Arthritis Scale ( WOMAC ) Pain , Stiffness , Physical Function VAS subscales , Patient and Physician Global Assessment of Therapy , Sleep , dropouts due to insufficient therapeutic effect , and adverse events . Two hundred forty-six patients were r and omized ( tramadol ER 124 , placebo 122 ) . There were no baseline differences between the two treatments . The mean age was 61 years , mean duration of OA 12.9 years , and the mean tramadol ER dose was 276 mg QD . All efficacy outcome measures favored tramadol ER over placebo . On the primary outcome variable of average change from baseline in Arthritis Pain Intensity VAS over 12 weeks , tramadol ER was superior to placebo ( least squares mean change from baseline : 30.4 mm vs. 17.7 mm , P < 0.001 ) . Significant differences from placebo were evident at week 1 , the first post-treatment visit . Similarly , outcomes on the WOMAC Pain , Stiffness and Physical Function subscales , the WOMAC Composite Scale , dropouts due to insufficient therapeutic effect , Patient and Physician Global Assessment of Therapy , and Sleep were all significantly better with tramadol ER than placebo ( P < 0.001 to < 0.05 ) . Treatment with tramadol ER results in statistically significant and clinical ly important and sustained improvements in pain , stiffness , physical function , global status , and sleep in patients with chronic pain . A once-a-day formulation of tramadol has the potential to provide patients increased control over the management of their pain , fewer interruptions in sleep and improved compliance We studied the efficacy and tolerability of glycosaminoglycan polysulfuric acid ( GAGPS ) in 80 patients with osteoarthritis ( OA ) of the knee . Patients received two series of five intra-articular injections , at 1-week intervals , of 25 mg ( 0.5 ml ) GAGPS into the knee in a double-blind , parallel , r and omized , placebo-controlled trial . There was an immediate decrease in pain after the injections of 43 % with GAGPS and 33 % with place Output:

Conclusions Work-related outcomes are rarely reported in journal publication on r and omized , double blind , placebo-controlled trials of h and , hip or knee OA .

MS214107

***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 multicenter phase II trial was conducted to define the activity of letrozole in postmenopausal women with recurrent or advanced endometrial carcinoma , who had no more than one prior line of progestins and never had chemotherapy ( except adjuvant ) . Archival paraffin-embedded tumor sample s were retrieved to determine the expression level of estrogen ( ER ) and progesterone receptor ( PgR ) , p53 , HER-2 , bcl-2 and PTEN protein , and phosphorylation status of protein kinase B ( PKB/Akt ) . Thirty-two eligible patients were treated with letrozole at 2.5 mg daily continuously , of whom 10 ( 31 % ) had prior progestins . Of the 28 patients evaluated for response , one complete and two partial responses were noted ; overall response was 9.4 % ( 95 % confidence interval 2–25 % ) . Eleven patients had stable disease for a median duration of 6.7 months ( range 3.7–19.3 months ) . Amongst 22 patients who had tumor blocks available , the proportion showing positive expression of the following markers includes : PgR ( 86 % ) , ER ( 86 % ) , PTEN ( 82 % ) , phosphorylated PKB/Akt ( 59 % ) , bcl-2 ( 45 % ) , p53 ( 32 % ) , and HER-2 ( 0 % ) . None of these markers correlated with response to letrozole or disease progression . In conclusion , letrozole is well tolerated but has little overall activity in this cohort of women with endometrial cancer Background We evaluated the efficacy and safety of the aromatase inhibitor exemestane in patients with advanced , persistent or recurrent endometrial carcinoma . Methods We performed an open-label one-arm , two-stage , phase II study of 25 mg of oral exemestane in 51 patients with advanced ( FIGO stage III-IV ) or relapsed endometrioid endometrial cancer . Patients were stratified into subsets of estrogen receptor ( ER ) positive and ER negative patients . Results Recruitment to the ER negative group was stopped prematurely after 12 patients due to slow accrual . In the ER positive patients , we observed an overall response rate of 10 % , and a lack of progression after 6 months in 35 % of the patients . No responses were registered in the ER negative patients , and all had progressive disease within 6 months . For the total group of patients , the median progression free survival ( PFS ) was 3.1 months ( 95 % CI : 2.0 - 4.1 ) . In the ER positive patients the median PFS was 3.8 months ( 95 % CI : 0.7 - 6.9 ) and in the ER negative patients it was 2.6 months ( 95 % CI : 2.1 - 3 - 1 ) . In the ER positive patients the median overall survival ( OS ) time was 13.3 months ( 95 % CI : 7.7 - 18.9 ) , in the ER negative patients the corresponding numbers were 6.1 months ( 95 % CI : 4.1 - 8.2 ) . Treatment with exemestane was well tolerated . Conclusion Treatment of estrogen positive advanced or recurrent endometrial cancer with exemestane , an aromatase inhibitor , result ed in a response rate of 10 % and lack of progression after 6 months in 35 % of the patients .Trial registration Trial identification number ( Clinical Trials.gov ) : NCT01965080.Nordic Society of Gynecological Oncology : NSGO – EC–0302.EudraCT number : 2004 - 001103 - 35 OBJECTIVES The objectives of this study were to estimate the clinical response rate and toxicity of daily tamoxifen combined with intermittent weekly medroxyprogesterone acetate ( MPA ) . METHODS This study reports the results of 61 patients with measurable advanced or recurrent endometrial carcinoma enrolled on this study to be treated with tamoxifen 40 mg p.o . daily plus alternating weekly cycles of MPA 200 mg p.o . daily . RESULTS One patient was excluded and two patients did not receive study treatment . The percent of patients responding ( 6 complete and 13 partial ) was 33 % ( 95 % confidence interval [ CI ] : 21 - 46 % ) among 58 eligible patients who received therapy . Median progression-free survival ( PFS ) was 3 months and median overall survival ( OS ) was 13 months . CONCLUSION The combination of daily tamoxifen and intermittent weekly medroxyprogesterone acetate is an active treatment for advanced or recurrent endometrial carcinoma . Further investigation of this combination is appropriate Advanced uterine leiomyosarcoma ( ULMS ) is an incurable disease . A significant percentage of cases of ULMS express estrogen and /or progesterone receptors ( ER and /or PR ) . To the authors ' knowledge , the role of estrogen suppression in disease management is not known BACKGROUND Some endometrial cancers are hormonally dependent . A principal source of circulating estrogen is conversion of adrenal and rostenedione by aromatase . Anastrozole ( Arimidex ) is an oral nonsteroidal aromatase inhibitor which is active in recurrent breast cancer . This Phase II study was undertaken to evaluate anastrozole in recurrent endometrial carcinoma . METHODS Patients with advanced or recurrent endometrial cancer not curable with either surgery or radiation therapy and with measurable disease , a GOG ( Zubrod ) performance status of < or = 2 , no more than one prior hormonal therapy regimen , and no prior chemotherapy were eligible . Anastrozole was administered at a dose of 1 mg/day orally for at least 28 days . RESULTS Twenty-three patients were entered on this trial . On central pathology review , 9 of them had grade 2 and 14 had grade 3 tumors . One to 24 courses ( median : 1 ) of therapy were administered . Two partial responses were noted ( 9 % ; 90 % confidence interval 3 to 23 % ) . Two additional patients had short-term stable disease . With the exception of 1 case of venous thrombosis , the toxicity profile was mild . Median duration s of progression-free survival and overall survival are 1 and 6 months , respectively . CONCLUSIONS Anastrozole has minimal activity in an unselected population of patients with recurrent endometrial cancer Estrogen-only menopausal hormone therapy ( HT ) increases the risk of endometrial cancer , but less is known about the association with other types of HT . Using Cox proportional hazards regression , the authors examined the association of various types of HT with the risk of endometrial cancer among 115,474 postmenopausal women recruited into the European Prospect i ve Investigation into Cancer and Nutrition between 1992 and 2000 . After a mean follow-up period of 9 years , 601 incident cases of endometrial cancer were identified . In comparison with never users of HT , risk of endometrial cancer was increased among current users of estrogen-only HT ( hazard ratio ( HR ) = 2.52 , 95 % confidence interval ( CI ) : 1.77 , 3.57 ) , tibolone ( HR = 2.96 , 95 % CI : 1.67 , 5.26 ) , and , to a lesser extent , estrogen-plus-progestin HT ( HR = 1.41 , 95 % CI : 1.08 , 1.83 ) , although risks differed according to regimen and type of progestin constituent . The association of HT use with risk was stronger among women who were older , leaner , or had ever smoked cigarettes . The finding of a strong increased risk of endometrial cancer with estrogen-only HT and a weaker association with combined HT supports the hypothesis that progestins have an attenuating effect on endometrial cancer risk . The increased risk associated with tibolone use requires further investigation We have studied the response rates and survival of a group of 93 patients with Stage III or IV endometrial adenocarcinoma after r and om allocation to therapy with tamoxifen ( TAM ) 20 mg twice daily ( n = 45 ) or medroxyprogesterone acetate ( MPA ) 1 g/wk intramuscularly ( n = 48 ) . The patients were examined every 4 months . In the non-responders and in those who relapsed , combination therapy with TAM and MPA was given . Twenty-four of 45 ( 53.4 % ) responded to TAM alone , 27 of 48 ( 56.2 % ) responded to MPA alone . Of the responders 23 later relapsed in the TAM group and 24 in the MPA group and of these 14 ( 60.8 % ) and 15 ( 62.5 % ) , respectively , responded to the combination therapy . Of the original 21 non-responders to MPA alone , 10 responded to the combination ( 47.6 % ) and 11 ( 52.4 % ) did not ; the comparable figures for the TAM alone group were 13 ( 61.9 % ) and 8 ( 38.1 % ) , respectively . Survival rates were much higher in the differentiated than in the undifferentiated carcinomas . In conclusion , we feel that the efficacy , and the few side-effects of these drugs used alone and particularly when used in sequential combination , make them a very attractive treatment for advanced endometrial adenocarcinoma The author presents a hypothesis that the complex of endocrine and metabolic disturbances arising long before the development of endometrial carcinoma determines the biological peculiarities of the tumor , its clinical course , and the prognosis of the disease . On the basis of a prospect i ve study of 366 patients with endometrial carcinoma , the author postulates that there are two different pathogenetic types of endometrial carcinoma . The first pathogenetic type of the disease arises in women with obesity , hyperlipidemia , and signs of hyperestrogenism : anovulatory uterine bleeding , infertility , late onset of the menopause , and hyperplasia of the stroma of the ovaries and endometrium . The second pathogenetic type of the disease arises in women who have no signs stated above or these signs are not clearly defined . The frequency of the first pathogenetic type in the studied group of women was 65 % , whereas the frequency of the second type was 35 % . The peculiarities outlined above which are characteristic of the first pathogenetic type of the disease determine the development of highly and moderately differentiated tumors ( 82.3 % G1 and G2 ) , superficial invasion of the myometrium ( 69.4 % ) , high sensitivity to progestogens ( 80.2 % ) , and favorable prognosis ( 85.6 % 5-year survival rate ) . In patients who have the second pathogenetic type of endometrial cancer when endocrine and metabolic disturbances are absent or occult , poorly differentiated tumors arise ( 62.5 % G3 ) , a tendency to deep invasion of tumor into the myometrium is observed ( 65.7 % ) ; high frequency of metastatic spread into the pelvic lymph nodes ( 27.8 % ) ; decrease of sensitivity to progestogens ( 42.5 % ) ; and doubtful prognosis ( 58.8 % 5-year survival rate ) are noted We evaluated the therapeutic value of sequential cyclical hormonal therapy ( megestrol acetate , and tamoxifen citrate ) plus single-agent chemotherapy ( carboplatin ) in the outpatient management of advanced or recurrent endometrial cancer . Carboplatin ( 300 mg/m2 ) was administered every 4 weeks for six courses or until disease progression . In addition , patients alternated megestrol acetate ( 80 mg orally twice daily ) with tamoxifen citrate ( 20 mg orally twice daily ) every 3 weeks . Thirteen of 18 ( 72.2 % ) patients were considered evaluable . Four patients ( 30.8 % ) had a complete response , six ( 46.2 % ) had a partial response , one ( 7.7 % ) had stable disease , and two patients ( 15.4 % ) progressed . Six of seven patients with vaginal disease responded . The median progression-free interval was 14 months for complete responders . Two patients ( 15.4 % ) are alive with no evidence of disease at 41 and 59 months . Seven of 13 patients experienced a hematologic toxicity ( six grade 2 , one grade 3 ) ; all resolved within 2 weeks . Dose reduction of carboplatin to 200 mg/m2 was required in one patient . No other toxicities were encountered . The median survival for all patients is 11 months , and is 33 months for complete responders . We conclude that a regimen of carboplatin plus sequential hormonal therapy shows promise in this pilot study for the treatment of advanced or recurrent endometrial cancer PURPOSE Progestins represent the most widely used form of endocrine therapy in advanced or recurrent endometrial carcinoma . Based on encouraging response rates in breast cancer with high-dose megestrol acetate ( MA ) 800 mg/d , this phase II trial assessed response rates in patients with endometrial carcinoma treated with high-dose MA . PATIENTS AND METHODS Sixty-three patients with recurrent or advanced endometrial carcinoma were entered into this Gynecologic Oncology Group ( GOG ) study . Patients had either failed to respond to or were considered incurable with local therapy and had not received prior cytotoxic or hormonal therapy . MA 800 mg/d was administered orally in divided Output:

Toxicity consisted mainly of nausea and thrombotic events and was higher in combination therapy of chemotherapy and hormonal therapy and hormonal therapy and mTOR inhibitors compared to other therapies . Conclusion : Tamoxifen or a combination of tamoxifen and progestin should be the preferred choice when selecting second line hormonal treatment because the RRs are similar to first line progestin treatment and the toxicity is low .

MS214108

***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: Potatoes have the highest daily per capita consumption of all vegetables in the U.S. diet . Pigmented potatoes contain high concentrations of antioxidants , including phenolic acids , anthocyanins , and carotenoids . In a single-dose study six to eight microwaved potatoes with skins or a comparable amount of refined starch as cooked biscuits was given to eight normal fasting subjects ; repeated sample s of blood were taken over an 8 h period . Plasma antioxidant capacity was measured by ferric reducing antioxidant power ( FRAP ) . A 24 h urine was taken before and after each regimen . Urine antioxidant capacity due to polyphenol was measured by Folin reagent after correction for nonphenolic interferences with a solid phase ( Polyclar ) procedure . Potato caused an increase in plasma and urine antioxidant capacity , whereas refined potato starch caused a decrease in both ; that is , it acted as a pro-oxidant . In a crossover study 18 hypertensive subjects with an average BMI of 29 were given either six to eight small microwaved purple potatoes twice daily or no potatoes for 4 weeks and then given the other regimen for another 4 weeks . There was no significant effect of potato on fasting plasma glucose , lipids , or HbA1c . There was no significant body weight increase . Diastolic blood pressure significantly decreased 4.3 % , a 4 mm reduction . Systolic blood pressure decreased 3.5 % , a 5 mm reduction . This blood pressure drop occurred despite the fact that 14 of 18 subjects were taking antihypertensive drugs . This is the first study to investigate the effect of potatoes on blood pressure . Thus , purple potatoes are an effective hypotensive agent and lower the risk of heart disease and stroke in hypertensive subjects without weight gain The consumption of cocoa and dark chocolate is associated with a lower risk of CVD , and improvements in endothelial function may mediate this relationship . Less is known about the effects of cocoa/chocolate on the augmentation index ( AI ) , a measure of vascular stiffness and vascular tone in the peripheral arterioles . We enrolled thirty middle-aged , overweight adults in a r and omised , placebo-controlled , 4-week , cross-over study . During the active treatment ( cocoa ) period , the participants consumed 37 g/d of dark chocolate and a sugar-free cocoa beverage ( total cocoa = 22 g/d , total flavanols ( TF ) = 814 mg/d ) . Colour-matched controls included a low-flavanol chocolate bar and a cocoa-free beverage with no added sugar ( TF = 3 mg/d ) . Treatments were matched for total fat , saturated fat , carbohydrates and protein . The cocoa treatment significantly increased the basal diameter and peak diameter of the brachial artery by 6 % ( + 2 mm ) and basal blood flow volume by 22 % . Substantial decreases in the AI , a measure of arterial stiffness , were observed in only women . Flow-mediated dilation and the reactive hyperaemia index remained unchanged . The consumption of cocoa had no effect on fasting blood measures , while the control treatment increased fasting insulin concentration and insulin resistance ( P= 0·01 ) . Fasting blood pressure ( BP ) remained unchanged , although the acute consumption of cocoa increased resting BP by 4 mmHg . In summary , the high-flavanol cocoa and dark chocolate treatment was associated with enhanced vasodilation in both conduit and resistance arteries and was accompanied by significant reductions in arterial stiffness in women Epidemiological studies indicate that habitual coffee consumption lowers the risk of diabetes and cardiovascular diseases . Postpr and ial hyperglycemia is a direct and independent risk factor for cardiovascular diseases . We previously demonstrated that coffee polyphenol ingestion increased secretion of Glucagon-like peptide 1 ( GLP-1 ) , which has been shown to exhibit anti-diabetic and cardiovascular effects . We hypothesized coffee polyphenol consumption may improve postpr and ial hyperglycemia and vascular endothelial function by increasing GLP-1 release and /or reducing oxidative stress . To examine this hypothesis , we conducted a r and omized , acute , crossover , intervention study in healthy male adults , measuring blood parameters and flow-mediated dilation ( FMD ) after ingestion of a meal with or without coffee polyphenol extract ( CPE ) . Nineteen subjects consumed a test meal with either a placebo- or CPE-containing beverage . Blood biomarkers and FMD were measured at fasting and up to 180 minutes postpr and ially . The CPE beverage led to a significantly lower peak postpr and ial increase in blood glucose and diacron-reactive oxygen metabolite , and significantly higher postpr and ial FMD than the placebo beverage . Postpr and ial blood GLP-1 increase tended to be higher after ingestion of the CPE beverage , compared with placebo . Subclass analysis revealed that the CPE beverage significantly improved postpr and ial blood GLP-1 response and reduced blood glucose increase in the subjects with a lower insulinogenic index . Correlation analysis showed postpr and ial FMD was negatively associated with blood glucose increase after ingestion of the CPE beverage . In conclusion , these results suggest that coffee polyphenol consumption improves postpr and ial hyperglycemia and vascular endothelial function , which is associated with increased GLP-1 secretion and decreased oxidative stress in healthy humans There is much epidemiological evidence suggesting a reduced risk of development of type 2 diabetes ( T2D ) in habitual coffee drinkers , however to date there have been few longer-term interventions , directly examining the effects of coffee intake on glucose and lipid metabolism . Previous studies may be confounded by inter-individual variation in caffeine metabolism . Specifically , the rs762551 SNP in the CYP1A2 gene has been demonstrated to influence caffeine metabolism , with carriers of the C allele considered to be of a ' slow ' metaboliser phenotype . This study investigated the effects of regular coffee intake on markers of glucose and lipid metabolism in coffee-naïve individuals , with novel analysis by rs762551 genotype . Participants were r and omised to either a coffee group ( n 19 ) who consumed four cups/d instant coffee for 12 weeks or a control group ( n 8) who remained coffee/caffeine free . Venous blood sample s were taken pre- and post-intervention . Primary analysis revealed no significant differences between groups . Analysis of the coffee group by genotype revealed several differences . Before coffee intake , the AC genotype ( ' slow ' caffeine metabolisers , n 9 ) displayed higher baseline glucose and NEFA than the AA genotype ( ' fast ' caffeine metabolisers , n 10 , P<0·05 ) . Post-intervention , reduced postpr and ial glycaemia and reduced NEFA suppression were observed in the AC genotype , with the opposite result observed in the AA genotype ( P<0·05 ) . These observed differences between genotypes warrant further investigation and indicate there may be no one-size-fits-all recommendation with regard to coffee drinking and T2D risk BACKGROUND Accumulating evidence suggests that certain dietary polyphenols have biological effects in the small intestine that alter the pattern of glucose uptake . Their effects , however , on glucose tolerance in humans are unknown . OBJECTIVE The objective was to investigate whether chlorogenic acids in coffee modulate glucose uptake and gastrointestinal hormone and insulin secretion in humans . DESIGN In a 3-way , r and omized , crossover study , 9 healthy fasted volunteers consumed 25 g glucose in either 400 mL water ( control ) or 400 mL caffeinated or decaffeinated coffee ( equivalent to 2.5 mmol chlorogenic acid/L ) . Blood sample s were taken frequently over the following 3 h. RESULTS Glucose and insulin concentrations tended to be higher in the first 30 min after caffeinated coffee consumption than after consumption of decaffeinated coffee or the control ( P < 0.05 for total and incremental area under the curve for glucose and insulin ) . Glucose-dependent insulinotropic polypeptide secretion decreased throughout the experimental period ( P < 0.005 ) , and glucagon-like peptide 1 secretion increased 0 - 120 min postpr and ially ( P < 0.01 ) after decaffeinated coffee consumption compared with the control . Glucose and insulin profiles were consistent with the known metabolic effects of caffeine . However , the gastrointestinal hormone profiles were consistent with delayed intestinal glucose absorption . CONCLUSIONS Differences in plasma glucose , insulin , and gastrointestinal hormone profiles further confirm the potent biological action of caffeine and suggest that chlorogenic acid might have an antagonistic effect on glucose transport . Therefore , a novel function of some dietary phenols in humans may be to attenuate intestinal glucose absorption rates and shift the site of glucose absorption to more distal parts of the intestine BACKGROUND AND OBJECTIVES Obesity has become a public health problem and is a cause of some preventable illnesses . Among several methods for treating obesity , the use of food supplements is highly common . A commonly used food supplement is green coffee bean extract . The objective of this study was to evaluate the efficacy of green coffee bean extract combined with an energy-restricted diet on the body composition and serum adipocytokines in obese women . METHODS AND STUDY DESIGN In this r and omised clinical trial , 64 obese women aged 20 - 45 years were selected and divided into two groups : an intervention group ( receiving 400 mg green coffee bean extract for 8 weeks ) and control group ( receiving placebo ) . All participants were on an energy-restricted diet . The body composition , leptin , adiponectin , lipid profile , free fatty acids ( FFAs ) , and fasting blood sugar were compared between the two groups . RESULTS We observed significant reductions in the body weight , body mass and fat mass indices , and waist-to-hip circumference ratio in both groups ; however , the decrease was higher in the intervention group . Moreover , serum total cholesterol , low-density lipoprotein , leptin , and plasma free fatty acids significantly decreased in the intervention group ( p<0.05 ) after adjustment for energy and fibre intake . The serum adiponectin concentration significantly increased in the intervention group ( p<0.05 ) . CONCLUSIONS Green coffee bean extract combined with an energy-restricted diet affects fat accumulation and lipid metabolism and is thus an inexpensive method for weight control in obese people Regular consumption of flavonoids may reduce the risk for CVD . However , the effects of individual flavonoids , for example , quercetin , remain unclear . The present study was undertaken to examine the effects of quercetin supplementation on blood pressure , lipid metabolism , markers of oxidative stress , inflammation , and body composition in an at-risk population of ninety-three overweight or obese subjects aged 25 - 65 years with metabolic syndrome traits . Subjects were r and omised to receive 150 mg quercetin/d in a double-blinded , placebo-controlled cross-over trial with 6-week treatment periods separated by a 5-week washout period . Mean fasting plasma quercetin concentrations increased from 71 to 269 nmol/l ( P < 0.001 ) during quercetin treatment . In contrast to placebo , quercetin decreased systolic blood pressure ( SBP ) by 2.6 mmHg ( P < 0.01 ) in the entire study group , by 2.9 mmHg ( P < 0.01 ) in the subgroup of hypertensive subjects and by 3.7 mmHg ( P < 0.001 ) in the subgroup of younger adults aged 25 - 50 years . Quercetin decreased serum HDL-cholesterol concentrations ( P < 0.001 ) , while total cholesterol , TAG and the LDL : HDL-cholesterol and TAG : HDL-cholesterol ratios were unaltered . Quercetin significantly decreased plasma concentrations of atherogenic oxidised LDL , but did not affect TNF-alpha and C-reactive protein when compared with placebo . Quercetin supplementation had no effects on nutritional status . Blood parameters of liver and kidney function , haematology and serum electrolytes did not reveal any adverse effects of quercetin . In conclusion , quercetin reduced SBP and plasma oxidised LDL concentrations in overweight subjects with a high-CVD risk phenotype . Our findings provide further evidence that quercetin may provide protection against CVD Chlorogenic acid has been described as a novel polyphenol with metabolic effects on glucose homeostasis . The aim of this study was to evaluate the effect of chlorogenic acid administration on glycemic control , insulin secretion , and insulin sensitivity in patients with impaired glucose tolerance ( IGT ) . A r and omized , double-blind , placebo-controlled clinical trial was performed in 30 patients with IGT ; 15 patients r and omly assigned to oral chlorogenic acid received 400 mg three times per day for 12 weeks , and the other 15 patients received placebo in the same way . Before and after the intervention , anthropometric and metabolic measurements , including fasting plasma glucose ( FPG ) , glycated hemoglobin A1c , and a lipid profile , were performed . Area under the curve of glucose and insulin as well as Output:

Results demonstrated that health status is a potentially important effect modifier as RCTs with higher baseline cholesterol , blood pressure and glycaemia demonstrated greater overall effectiveness , which was also found in studies where specific subgroup analyses were performed .

MS214109

***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: CONTEXT Allogeneic blood transfusions have immunomodulatory effects and have been associated with activation of human immunodeficiency virus ( HIV ) and cytomegalovirus ( CMV ) in vitro and of HIV in small pilot studies . Retrospective studies suggest that transfusions adversely affect the clinical course of HIV . Data in selected non-HIV-infected patients requiring blood transfusion have suggested clinical benefit with leukocyte-reduced red blood cells ( RBCs ) . OBJECTIVE To compare the effects of leukoreduced and unmodified RBC transfusions on survival , complications of acquired immunodeficiency syndrome , and relevant laboratory markers in HIV-infected patients . DESIGN AND SETTING Double-blind r and omized controlled trial conducted in 11 US academic medical centers from July 1995 through June 1999 , with a median follow-up of 12 months ( 24 months in survivors ) . PATIENTS A total of 531 persons infected with HIV and CMV , aged 14 years or older , who required transfusions for anemia ; 259 received leukoreduced transfusions and 262 received unmodified transfusions ( 10 did not receive the planned transfusion ) . MAIN OUTCOME MEASURES Survival and change in plasma HIV RNA level 7 days after transfusion , compared by type of transfusion . RESULTS At entry , the groups were similar in demographic , clinical , and relevant laboratory characteristics . A total of 3864 RBC units were transfused . Two hundred eighty-nine deaths occurred ( 151 with leukoreduced transfusion ; 138 with unmodified transfusion ) ; median survival was 13.0 and 20.5 months , respectively ( relative hazard [ RH ] , 1.20 ; 95 % confidence interval [ CI ] , 0.95 - 1.51 ; log-rank P = .12 ) . Analyses adjusted for prognostic factors suggested possible worse survival with leukoreduction ( RH , 1.35 ; 95 % CI , 1.06 - 1.72 ) . There was no difference in time to new opportunistic event/death or frequency of transfusion reactions . No changes in plasma HIV RNA level were seen in either group at days 7 , 14 , 21 , or 28 , even in patients not taking antiretroviral drugs . There were no differences in trends between groups in CMV DNA , CD4 cell counts , activated ( CD38 % or human leukocyte antigen-DR ) CD8 cell counts , or plasma cytokine levels . CONCLUSIONS We found no evidence of HIV , CMV , or cytokine activation following blood transfusion in patients with advanced HIV infection . Leukoreduction provided no clinical benefit in these patients . These data demonstrate the importance of conducting controlled studies of effects of leukoreduction in different patient population s , since smaller studies in other patient population s have suggested leukoreduction may be beneficial Background —Leukocytes in allogeneic blood transfusions are believed to be the cause of immunomodulatory events . A few trials on leukocyte removal from transfusions in cardiac surgery have been conducted , and they showed inconclusive results . We found in a previous study a decrease in mortality rates and number of infections in a subgroup of more heavily transfused patients . Methods and Results — Patients ( n= 496 ) undergoing valve surgery ( with or without CABG ) were r and omly assigned in a double-blind fashion to receive st and ard buffy coat – depleted ( PC ) or prestorage , by filtration , leukocyte-depleted erythrocytes ( LD ) . The primary end point was mortality at 90 days , and secondary end points were in-hospital mortality , multiple organ dysfunction syndrome , infections , intensive care unit stay , and hospital stay . The difference in mortality at 90 days was not significant ( PC 12.7 % versus LD 8.4 % ; odds ratio [ OR ] , 1.52 ; 95 % confidence interval [ CI ] , 0.84 to 2.73 ) . The in-hospital mortality rate was almost twice as high in the PC group ( 10.1 % versus 5.5 % in the LD group ; OR , 1.99 ; 95 % CI , 0.99 to 4.00 ) . The incidence of multiple organ dysfunction syndrome in both groups was similar , although more patients with multiple organ dysfunction syndrome died in the PC group . LD was associated with a significantly reduced infection rate ( PC 31.6 % versus LD 21.6 % ; OR , 1.64 ; 95 % CI , 1.08 to 2.49 ) . In both groups , intensive care unit stay and hospital stay were similar , and postoperative complications increased with the number of transfused units . Conclusions —Mortality at 90 days was not significantly different ; however , a beneficial effect of LD in valve surgery was found for the secondary end points of in-hospital mortality and infections OBJECTIVE In elective orthopaedic hip- and knee replacement surgery patients , we studied the effect of implementation of a uniform transfusion policy on RBC usage . STUDY DESIGN AND METHODS A r and omized , controlled study . A new uniform , restrictive transfusion policy was compared with st and ard care , which varied among the three participating hospitals . Only prestorage leucocyte-depleted RBC(s ) were used . Primary end-point was RBC usage , related to length of hospital stay . Secondary end-points were Hb levels , mobilization delay and postoperative complications . RESULTS Six hundred and three patients were evaluated . Adherence to the protocol was over 95 % . Overall mean RBC usage was 0.78 U/patient in the new policy group and 0.86 U/patient in the st and ard care policy group ( mean difference 0.08;95 % CI [ -0.3 ; 0.2 ] ; P = 0.53 ) . In two hospitals , the new transfusion policy result ed in a RBC reduction of 30 % ( 0.58U RBC/patient ) ( P = 0.17 ) and 41 % ( 0.29 U RBC/patient ) ( P = 0.05 ) respectively . In the third hospital , however , RBC usage increased by 39 % ( 0.31 U RBC/patient ) ( P = 0.02 ) with the new policy , due to a more restrictive st and ard care policy in that hospital . Length of hospital stay was not influenced by either policy . CONCLUSIONS Implementation of a uniform transfusion protocol for elective lower joint arthroplasty patients is feasible , but does not always lead to a RBC reduction . Length of hospital stay was not affected Perioperative blood transfusions are reported to be related to cancer recurrence and reduced survival . Different underlying mechanisms have been proposed , and allogeneic leucocytes in transfused blood have been suggested to contribute to this phenomenon BACKGROUND Blood cardioplegia ( BCP ) is widely used for myocardial protection during open heart operation . However , BCP may have a chance to induce neutrophil-mediated myocardial injury during aortic cross-clamping . We clinical ly evaluated the myocardial protective effect of leukocyte-depleted blood cardioplegia ( LDBCP ) for initial and intermittent BCP administration in pediatric patients . METHODS Fifty patients undergoing open heart operation for congenital heart disease between January 1997 and March 1999 were review ed . Twenty-five were administered LDBCP for myocardial protection during ischemic periods ( LDBCP group ) , and the remaining 25 were given BCP without leukocyte depletion ( BCP group ) . RESULTS The difference in plasma concentrations of malondialdehyde between coronary sinus effluent blood and arterial blood just after reperfusion in the LDBCP group ( 1.68 + /- 0.56 micromol/L ) was significantly lower than that in the BCP group ( 2.35 + /- 0.62 micromol/L ; p < 0.01 ) . The LDBCP group showed significantly lower plasma concentrations of human heart fatty acid-binding protein at 50 minutes after reperfusion ( LDBCP group , 103.5 + /- 38.7 IU/L ; BCP group , 144.8 + /- 48.8 IU/L ; p < 0.01 ) and the peak value of creatine kinase-MB during the first 24 postoperative hours ( LDBCP group , 17.0 + /- 8.5 IU/L ; BCP group , 26.0 + /- 11.6 IU/L ; p < 0.01 ) than did the BCP group . The maximum dose of catecholamine was significantly smaller in the LDBCP group ( LDBCP group , 3.20 + /- 2.18 microg x kg(-1 ) x min(-1 ) ; BCP group , 5.60 + /- 2.83 microg x kg(-1 ) x min(-1 ) ; p < 0.01 ) . CONCLUSIONS These results suggest the usefulness of LDBCP for protection from the myocardial injury that can be induced by BCP administration during aortic cross-clamping Introduction Microvascular alterations impair tissue oxygenation during sepsis . A red blood cell ( RBC ) transfusion increases oxygen ( O2 ) delivery but rarely improves tissue O2 uptake in patients with sepsis . Possible causes include RBC alterations due to prolonged storage or residual leukocyte-derived inflammatory mediators . The aim of this study was to compare the effects of two types of transfused RBCs on microcirculation in patients with sepsis . Methods In a prospect i ve r and omized trial , 20 patients with sepsis were divided into two separate groups and received either non-leukodepleted ( n = 10 ) or leukodepleted ( n = 10 ) RBC transfusions . Microvascular density and perfusion were assessed with sidestream dark field ( SDF ) imaging sublingually , before and 1 hour after transfusions . Thenar tissue O2 saturation ( StO2 ) and tissue hemoglobin index ( THI ) were determined with near-infrared spectroscopy , and a vascular occlusion test was performed . The microcirculatory perfused boundary region was assessed in SDF images as an index of glycocalyx damage , and glycocalyx compounds ( syndecan-1 , hyaluronan , and heparan sulfate ) were measured in the serum . Results No differences were observed in microvascular parameters at baseline and after transfusion between the groups , except for the proportion of perfused vessels ( PPV ) and blood flow velocity , which were higher after transfusion in the leukodepleted group . Microvascular flow index in small vessels ( MFI ) and blood flow velocity exhibited different responses to transfusion between the two groups ( P = 0.03 and P = 0.04 , respectively ) , with a positive effect of leukodepleted RBCs . When within-group changes were examined , microcirculatory improvement was observed only in patients who received leukodepleted RBC transfusion as suggested by the increase in De Backer score ( P = 0.02 ) , perfused vessel density ( P = 0.04 ) , PPV ( P = 0.01 ) , and MFI ( P = 0.04 ) . Blood flow velocity decreased in the non-leukodepleted group ( P = 0.03 ) . THI and StO2 upslope increased in both groups . StO2 and StO2 downslope increased in patients who received non-leukodepleted RBC transfusions . Syndecan-1 increased after the transfusion of non-leukodepleted RBCs ( P = 0.03 ) . Conclusions This study does not show a clear superiority of leukodepleted over non-leukodepleted RBC transfusions on microvascular perfusion in patients with sepsis , although it suggests a more favorable effect of leukodepleted RBCs on microcirculatory convective flow . Further studies are needed to confirm these findings .Trial registration Clinical Trials.gov , The frequency of infection in 197 patients undergoing elective colorectal surgery and having either no blood transfusion , transfusion with whole blood , or filtered blood free from leucocytes and platelets was investigated in a prospect i ve r and omized trial . Natural killer cell function was measured before operation and 3 , 7 and 30 days after surgery in 60 consecutive patients . Of the patients 104 required blood transfusion ; 48 received filtered blood and 56 underwent whole blood transfusion . Postoperative infections developed in 13 patients transfused with whole blood ( 23 per cent , 9.5 per cent confidence interval 13–32 per cent ) , in one patient transfused with blood free from leucocytes and platelets ( 2 per cent , 9.5 per cent confidence interval 0.05–11 per cent ) and in two non‐transfused patients ( 2 per cent , 95 per cent conjidence interval 0.3‐8per cent ) ( P < 0.01 ) . Natural killer cell function was significantly ( P < 0.001 ) impaired up to 30 days after surgery in patients transfused with whole blood . These data provide a strong case against the use of whole blood transfusion in patients undergoing elective colorectal surgery We performed a prospect i ve , r and omized trial in CMV seronegative marrow recipients to determine if filtered blood products were as effective as CMV-seronegative blood products for the prevention of transfusion-transmitted CMV infection after marrow trans Output:

There is no clear evidence for supporting or rejecting the routine use of leukoreduction in all patients requiring PRBC transfusion for preventing TRALI , death , infection , non-infectious complications and other adverse events .

MS214110

***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 aim ed to replicate findings that alcohol consumption and positive implicit beer-related cognitions can be reduced using inhibitory control ( IC ) training , with the addition of an active training control . Frontal EEG asymmetry , an objective psychophysiological index of approach motivation , was used as a dependent measure to examine training outcomes . Participants were r and omly assigned to one of two IC training conditions ( Beer NoGo or Beer Go ) or a Brief Alcohol Intervention ( BAI ) ( i.e. the active training control ) . The IC training tasks consistently paired a stimulus that required a response with images of water ( Beer NoGo ) or images of beer ( Beer Go ) . Alcohol consumption and implicit beer-related cognitions were measured at pre-training , post-training and at one week follow-up . Frontal EEG asymmetry was recorded during a passive image viewing task that presented neutral , healthy , and beer stimuli - at pre-training , post-training and follow-up . Participants in the Beer NoGo and BAI conditions consumed less beer in a taste test immediately after training than Beer Go participants , suggesting that IC training may be as effective as the already established BAI . The taste test findings were in line with the frontal EEG asymmetry data , which indicated that approach motivation for beer stimuli was altered in the expected directions . However , the positive correlation between post-training frontal EEG asymmetry data and taste test consumption was not significant . While there were no significant changes in implicit beer-related cognitions following training , a trending positive relationship between implicit beer-related cognitions at post-training and taste test consumption was reported . Further exploration addressing the limitations of the current study is required in order to clarify the implication s of these findings Rationale Both cue avoidance training ( CAT ) and inhibitory control training ( ICT ) reduce alcohol consumption in the laboratory . However , these interventions have never been directly compared and their mechanisms of action are poorly understood . Objectives We compared the effects of both types of training on alcohol consumption and investigated if they led to theoretically predicted changes in alcohol avoidance ( CAT ) or alcohol inhibition ( ICT ) associations and changes in evaluation of alcohol cues . Methods Heavy drinking young adults ( N = 120 ) were r and omly assigned to one of four groups : ( 1 ) CAT ( repeatedly pushing alcohol cues away with a joystick ) , ( 2 ) sham ( control ) CAT ; ( 3 ) ICT ( repeatedly inhibiting behaviour in response to alcohol cues ) ; or ( 4 ) sham ( control ) ICT . Changes in reaction times and automatic evaluations of alcohol cues were assessed before and after training using assessment versions of tasks used in training and the implicit association test ( IAT ) , respectively . Finally , participants completed a bogus taste test as a measure of ad libitum alcohol consumption . Results Compared to sham conditions , CAT and ICT both led to reduced alcohol consumption although there was no difference between the two . Neither intervention affected performance on the IAT , and changes in reaction time did not suggest the formation of robust alcohol avoidance ( CAT ) or alcohol inhibition ( ICT ) associations after training . Conclusions CAT and ICT yielded equivalent reductions in alcohol consumption in the laboratory . However , these behavioural effects were not accompanied by devaluation of stimuli or the formation of alcohol avoidance or alcohol inhibition associations BACKGROUND Young adult heavy drinking is an important public health concern . Current interventions have efficacy but with only modest effects , and thus , novel interventions are needed . In prior studies , heavy drinkers , including young adults , have demonstrated stronger automatically triggered approach tendencies to alcohol-related stimuli than lighter drinkers . Automatic action tendency retraining has been developed to correct this tendency and consequently reduce alcohol consumption . This study is the first to test multiple iterations of automatic action tendency retraining , followed by laboratory alcohol self-administration . METHODS A total of 72 nontreatment-seeking , heavy drinking young adults ages 21 to 25 were r and omized to automatic action tendency retraining or a control condition ( i.e. , " sham training " ) . Of these , 69 ( 54 % male ) completed 4 iterations of retraining or the control condition over 5 days with an alcohol drinking session on Day 5 . Self-administration was conducted according to a human laboratory paradigm design ed to model individual differences in impaired control ( i.e. , difficulty adhering to limits on alcohol consumption ) . RESULTS Automatic action tendency retraining was not associated with greater reduction in alcohol approach tendency or less alcohol self-administration than the control condition . The laboratory paradigm was probably sufficiently sensitive to detect an effect of an experimental manipulation given the range of self-administration behavior observed , both in terms of number of alcoholic and nonalcoholic drinks and measures of drinking topography . CONCLUSIONS Automatic action tendency retraining was ineffective among heavy drinking young adults without motivation to change their drinking . Details of the retraining procedure may have contributed to the lack of a significant effect . Despite null primary findings , the impaired control laboratory paradigm is a valid laboratory-based measure of young adult alcohol consumption that provides the opportunity to observe drinking topography and self-administration of nonalcoholic beverages ( i.e. , protective behavioral strategies directly related to alcohol use ) There is preliminary evidence that approach avoid training can shift implicit alcohol associations and improve treatment outcomes . We sought to replicate and extend those findings in US undergraduate social drinkers ( Study 1 ) and at-risk drinkers ( Study 2 ) . Three adaptations of the approach avoid task ( AAT ) were tested . The first adaptation – the approach avoid training – was a replication and targeted implicit alcohol approach associations . The remaining two adaptations – the general identity and personalized identity trainings – targeted implicit drinking identity associations , which are robust predictors of hazardous drinking in US undergraduates . Study 1 included 300 undergraduate social drinkers . They were r and omly assigned to real or sham training conditions for one of the three training adaptations , and completed two training sessions , spaced one week apart . Study 2 included 288 undergraduates at risk for alcohol use disorders . The same training procedures were used , but the two training sessions occurred within a single week . Results were not as expected . Across both studies , the approach avoid training yielded no evidence of training effects on implicit alcohol associations or alcohol outcomes . The general identity training also yielded no evidence of training effects on implicit alcohol associations or alcohol outcomes with one exception ; individuals who completed real training demonstrated no changes in drinking refusal self-efficacy whereas individuals who completed sham training had reductions in self-efficacy . Finally , across both studies , the personalized identity training yielded no evidence of training effects on implicit alcohol associations or alcohol outcomes . Despite having relatively large sample s and using a well-vali date d training task , study results indicated all three training adaptations were ineffective at this dose in US undergraduates . These findings are important because training studies are costly and labor-intensive . Future research may benefit from focusing on more severe population s , pairing training with other interventions , increasing training dose , and increasing gamification of training tasks CONTEXT Alcohol dependence treatment may include medications , behavioral therapies , or both . It is unknown how combining these treatments may impact their effectiveness , especially in the context of primary care and other nonspecialty setting s. OBJECTIVES To evaluate the efficacy of medication , behavioral therapies , and their combinations for treatment of alcohol dependence and to evaluate placebo effect on overall outcome . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial conducted January 2001-January 2004 among 1383 recently alcohol-abstinent volunteers ( median age , 44 years ) from 11 US academic sites with Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , diagnoses of primary alcohol dependence . INTERVENTIONS Eight groups of patients received medical management with 16 weeks of naltrexone ( 100 mg/d ) or acamprosate ( 3 g/d ) , both , and /or both placebos , with or without a combined behavioral intervention ( CBI ) . A ninth group received CBI only ( no pills ) . Patients were also evaluated for up to 1 year after treatment . MAIN OUTCOME MEASURES Percent days abstinent from alcohol and time to first heavy drinking day . RESULTS All groups showed substantial reduction in drinking . During treatment , patients receiving naltrexone plus medical management ( n = 302 ) , CBI plus medical management and placebos ( n = 305 ) , or both naltrexone and CBI plus medical management ( n = 309 ) had higher percent days abstinent ( 80.6 , 79.2 , and 77.1 , respectively ) than the 75.1 in those receiving placebos and medical management only ( n = 305 ) , a significant naltrexone x behavioral intervention interaction ( P = .009 ) . Naltrexone also reduced risk of a heavy drinking day ( hazard ratio , 0.72 ; 97.5 % CI , 0.53 - 0.98 ; P = .02 ) over time , most evident in those receiving medical management but not CBI . Acamprosate showed no significant effect on drinking vs placebo , either by itself or with any combination of naltrexone , CBI , or both . During treatment , those receiving CBI without pills or medical management ( n = 157 ) had lower percent days abstinent ( 66.6 ) than those receiving placebo plus medical management alone ( n = 153 ) or placebo plus medical management and CBI ( n = 156 ) ( 73.8 and 79.8 , respectively ; P<.001 ) . One year after treatment , these between-group effects were similar but no longer significant . CONCLUSIONS Patients receiving medical management with naltrexone , CBI , or both fared better on drinking outcomes , whereas acamprosate showed no evidence of efficacy , with or without CBI . No combination produced better efficacy than naltrexone or CBI alone in the presence of medical management . Placebo pills and meeting with a health care professional had a positive effect above that of CBI during treatment . Naltrexone with medical management could be delivered in health care setting s , thus serving alcohol-dependent patients who might otherwise not receive treatment . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00006206 BACKGROUND Alcoholism is a progressive neurocognitive developmental disorder . Recent evidence shows that computerized training interventions ( Cognitive Bias Modification , CBM ) can reverse some of these maladaptively changed neurocognitive processes . A first clinical study of a CBM , called alcohol-avoidance training , found that trained alcoholic patients showed less relapse at one-year follow-up than control patients . The present study tested the replication of this result , and questions about mediation and moderation . METHODS 509 alcohol-dependent patients received treatment as usual ( primarily Cognitive Behavior Therapy ) inpatient treatment . Before and after treatment , the implicit approach bias was measured with the Alcohol Approach-Avoidance Task . Half of the patients were r and omly assigned to CBM , the other half received treatment as usual only . Background variables , psychopathology and executive control were tested as possible moderating variables of CBM . One year after treatment , follow-up data about relapse were collected . RESULTS The group receiving CBM developed alcohol-avoidance behavior and reported significantly lower relapse rates at one-year follow-up . Change in alcohol-approach bias mediated this effect . Moderation analyses demonstrated that older patients and patients with a strong approach-bias at pretest profited most from CBM . CONCLUSIONS CBM is a promising treatment add-on in alcohol addiction and may counter some of the maladaptive neurocognitive effects of long-term alcoholism To examine the impact of a computer-delivered , home-based , alcohol-specific attention modification program ( AMP ) , 41 heavy drinking college students were r and omly assigned to AMP or an attention control condition ( ACC ) . Participants selected 10 alcohol-related words most relevant to their own drinking experience as well as 10 neutral words not related to alcohol . These personalized stimuli were used in an attention retaining program based upon the probe detection paradigm twice weekly for 4 weeks . Participants in the AMP condition reported decreased drinking , whereas those in the ACC condition reported no change in their drinking . These preliminary data suggest that a computer-delivered , home-delivered , attention-retraining for alcohol treatment may be an inexpensive and efficacious adjunct to st and ard alcohol treatments 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 Cognitive bias modification ( CBM ) can be used to retrain automatic approach tendencies for alcohol . We investigated whether changing cortical excitability with transcranial direct current stimulation ( tDCS ) could enhance CBM effects in hazardous drinkers . We also studied the underlying mechanisms by including behavioral ( craving , implicit associations , approach tendencies ) and electrophysiological ( event-related potentials ) measurements . METHODS The analytical sample consisted of 78 hazardous drinkers ( Alcohol Use Disorders Identification Test > 8) r and omly assigned to 4 conditions in a 2-by-2 factorial design ( control/active CBM and sham/active tDCS ) . The intervention consisted of 3 sessions of CBM , specifically alcohol approach bias retraining , combined with 15 minutes 1 mA tDCS over the left dorsolateral prefrontal cortex . There was a pre- and post assessment before and after the intervention that included experimental tasks ( Approach Avoidance Task , Implicit Association Task ) and an electroencephalogram with an oddball and cue-reactivity task . RESULTS tDCS decreased cue-induced craving ( but not overall craving ) on post assessment . CBM did not induce an Output:

Results : While AtBM seems to influence attentional bias , its effects on drinking behavior are inconsistent . As for ApBM , the best effects on drinking behavior are obtained in clinical sample s. Effects of ApBM on approach bias are mixed . Interestingly , those clinical RCTs which investigated ApBM effects on bias change as well as on drinking outcome , reported consistent effects in both measures ( i.e. either effects on bias and drinking or no effects ) . Studies on IT are limited to non- clinical sample s and show inconsistent effects on drinking behavior . Conclusions about the overall influence of drinking behavior severity are hampered by the non-uniform use of sample descriptions . Conclusions : In clinical sample s , ApBM has shown more consistent beneficial effects , while evidence on AtBM is more inconsistent , and data on IT still lacks important information . Conclusions about the influence of drinking behavior severity would be facilitated by a uniform use of clearly defined sample descriptions

MS214111

***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 Sugar-sweetened beverages and maternal weight are strong drivers of child obesity , but few studies have targeted these risk factors as an obesity prevention strategy in children . OBJECTIVE The objective of this study was to test the efficacy of a smartphone-delivered intervention to reduce parent-provided sugar-sweetened beverage and juice ( SSB/juice ) consumption among children ages 3 - 5 and maternal weight . METHODS Mothers with overweight or obesity , who had a child ages 3 - 5 that consumed at least 12 fl . oz./day of SSB/juice ( N = 51 dyads ) were r and omized to the Smart Moms group that received one group session , lessons on a mobile website , and text messages , or to a waitlist control group . Mothers self-monitored their children 's beverages in addition to their own beverages , high-calorie foods , and weight . Assessment s at baseline , 3 , and 6 months included dietary recalls to measure SSB/juice intake and objective ly measured maternal weight . RESULTS Using linear mixed models controlling for baseline values , child age and race , there was a greater reduction in child SSB/juice in Smart Moms compared with control at 6 months ( -9.7 oz./day vs. 1.7 oz./day , p < .01 ) . Mothers in Smart Moms lost 2.4 kg at 6 months compared with a 0.9-kg gain in the control group ( p < .01 ) . CONCLUSIONS An intervention delivered using mHealth technologies can target mothers to change child dietary behaviours and improve maternal weight , which suggests a novel approach to family-based obesity prevention OBJECTIVE . The study tested whether a combined environmental and educational intervention solely promoting water consumption was effective in preventing overweight among children in elementary school . METHODS . The participants in this r and omized , controlled cluster trial were second- and third- grade rs from 32 elementary schools in socially deprived areas of 2 German cities . Water fountains were installed and teachers presented 4 prepared classroom lessons in the intervention group schools ( N = 17 ) to promote water consumption . Control group schools ( N = 15 ) did not receive any intervention . The prevalence of overweight ( defined according to the International Obesity Task Force criteria ) , BMI SD scores , and beverage consumption ( in glasses per day ; 1 glass was defined as 200 mL ) self-reported in 24-hour recall question naires , were determined before ( baseline ) and after the intervention . In addition , the water flow of the fountains was measured during the intervention period of 1 school year ( August 2006 to June 2007 ) . RESULTS . Data on 2950 children ( intervention group : N = 1641 ; control group : N = 1309 ; age , mean ± SD : 8.3 ± 0.7 years ) were analyzed . After the intervention , the risk of overweight was reduced by 31 % in the intervention group , compared with the control group , with adjustment for baseline prevalence of overweight and clustering according to school . Changes in BMI SD scores did not differ between the intervention group and the control group . Water consumption after the intervention was 1.1 glasses per day greater in the intervention group . No intervention effect on juice and soft drink consumption was found . Daily water flow of the fountains indicated lasting use during the entire intervention period , but to varying extent . CONCLUSION . Our environmental and educational , school-based intervention proved to be effective in the prevention of overweight among children in elementary school , even in a population from socially deprived areas OBJECTIVE The purpose of the present study was to evaluate the effects of a school-based , 2-year , multi-component intervention on BMI , eating and physical activity behaviour in Fl and ers , Belgium , targeting children aged 3 - 6 years in communities of high and low socio-economic status ( SES ) . DESIGN Cluster-r and omized controlled trial . SETTING Thirty-one pre- primary and primary schools in three different intervention communities and three paired-matched ( on SES profile ) control communities in Fl and ers , Belgium . SUBJECTS BMI Z-scores at baseline and follow-up were calculated for 1102 children . Question naires with sociodemographic data and FFQ were available from 694 of these 1102 children . RESULTS No significant effects were found on BMI Z-scores for the total sample . However , there was a significant decrease in BMI Z-score of 0·11 in the low-SES intervention community compared with the low-SES control community , where the BMI Z-score increased by 0·04 ( F = 6·26 , P = 0·01 ) . No significant intervention effects could be found for eating behaviour , physical activity or screen-time . There were no significant interaction effects of age and gender of the children on the outcome variables . CONCLUSIONS Although no significant effects were found for BMI Z-scores in the total sample , this intervention had a promising effect in the low-SES community of reducing excess weight gain among young children Background The FAN Social Marketing program was developed to improve dietary and physical activity habits of families with children in Ticino , Switzerl and . The aim of this study was to examine if the effects of the program on children ’s food intake differed by intervention group . Methods Effects of the FAN program were tested through a R and omized Controlled Trial . The program lasted 8 weeks , during which participants received tailored communication about nutrition and physical activity . Families were r and omly allocated to one of three groups , where the parent received the intervention by the Web ( G1 ) , Web + e-mail ( G2 ) or Web + SMS ( G3 ) . Children in all groups received tailored print letters by post . Children ’s food consumption was assessed at baseline and immediate post intervention using a 7-day food diary . Generalized linear mixed models with child as a r and om effect and with time , treatment group , and the time by treatment interaction as fixed effects were used to test the impact of the intervention . Results Analyses were conducted with a sample of 608 children . After participating in FAN the marginal means of daily consumption of fruit changed from 0.95 to 1.12 in G1 , from 0.82 to 0.94 in G2 , and from 0.93 to 1.18 in G3 . The margins of the daily consumption of sweets decreased in each group ( 1.67 to 1.56 in G1 , 1.71 to 1.49 in G2 , and 1.72 to 1.62 in G3 ) . The change in vegetable consumption observed from pre to post intervention in G3 ( from 1.13 to 1.21 ) was significantly different from that observed in G1 ( from 1.21 to 1.17 ) . Conclusions A well- design ed Web-based Social Marketing intervention complemented with print letters can help improve children ’s consumption of water , fruit , soft drinks , and sweets . The use of SMS to support greater behavior change , in addition to Web-based communication , result ed only in a small significant positive change for vegetables , while the use of e-mail in addition to Web did not result in any significant difference . Trial registration The trial was retrospectively registered in the IS RCT N registry ( ID IS RCT N48730279 ) OBJECTIVE Consumption of water may help promote health and prevent obesity in children by decreasing consumption of sugar-sweetened beverages . This study used evidence -based strategies to increase water consumption in Mexican-American and Mexican children . MATERIAL S AND METHODS In 2012 , two schools in San Diego , USA and two other in Tlaltizapan , Mexico were recruited to Agua para Niños ( Water for Kids ) , a program design ed to promote water consumption among elementary grade students . Guided by operant psychology , the intervention focused on school and classroom activities to encourage water consumption . One control and one intervention school in each country were included . RESULTS Agua para Niños result ed in increases in observed water consumption and bottle possession among US and Mexican students . Teacher receptivity to the program was very positive in both countries . CONCLUSIONS Agua para Niños yielded sufficiently positive behavioral changes to be used in a future fully r and omized design , and to contribute to school nutrition policy changes The objective of this study was to evaluate an educational module for Latino parents about the health effects of sweet beverages . Latino parents were r and omized to receive the beverage module or a control module . Child beverage consumption was assessed at baseline , 2 weeks , 2 months , and 3 months via a beverage recall survey . At 2-week follow-up , children of intervention participants had a mean reduction in 7-day total sugar-sweetened beverage and 100 % fruit juice consumption of 16 ounces while controls had a mean increase of 4 ounces ( P = .01 ) . At 2-month and 3-month follow-up , there was a reduction in mean total sugar-sweetened beverage and 100 % fruit juice consumption among both intervention and control children . An educational module on beverages for Latino parents reduced child consumption of sweet beverages at 2-week follow-up . However , study participation appears to have also reduced controls ’ beverage consumption suggesting that frequent intensive surveys of beverage intake may be an intervention unto itself UNLABELLED The current pilot study examined the effectiveness of a social network-based intervention using peer influence on self-reported water consumption . A total of 210 children ( 52 % girls ; M age = 10.75 ± SD = 0.80 ) were r and omly assigned to either the intervention ( n = 106 ; 52 % girls ) or control condition ( n = 104 ; 52 % girls ) . In the intervention condition , the most influential children in each classroom were trained to promote water consumption among their peers for eight weeks . The schools in the control condition did not receive any intervention . Water consumption , sugar-sweetened beverage ( SSB ) consumption , and intentions to drink more water in the near future were assessed by self-report measures before and immediately after the intervention . A repeated measure MANCOVA showed a significant multivariate interaction effect between condition and time ( V = 0.07 , F(3 , 204 ) = 5.18 , p = 0.002 , pη(2 ) = 0.07 ) on the dependent variables . Further examination revealed significant univariate interaction effects between condition and time on water ( p = 0.021 ) and SSB consumption ( p = 0.015 ) as well as water drinking intentions ( p = 0.049 ) . Posthoc analyses showed that children in the intervention condition reported a significant increase in their water consumption ( p = 0.018 ) and a decrease in their SSB consumption ( p < 0.001 ) over time , compared to the control condition ( p-values > 0.05 ) . The children who were exposed to the intervention did not report a change in their water drinking intentions over time ( p = 0.576 ) whereas the nonexposed children decreased their intentions ( p = 0.026 ) . These findings show promise for a social network-based intervention using peer influence to positively alter consumption behaviors . TRIAL REGISTRATION This RCT was registered in the Australian New Zeal and Clinical Trials Registry ( ACTRN12614001179628 ) . Study procedures were approved by the Ethics Committee of the Faculty of Social Sciences at Radboud University ( ECSW2014 - 1003 - 203 ) INTRODUCTION Across the U.S. , afterschool programs ( ASPs , 3:00pm-6:00pm ) are trying to achieve nationally endorsed nutrition st and ards ( Healthy Eating St and ards ) calling for fruits/vegetables and water to be served every day , while eliminating sugar-sweetened beverages and foods . The purpose of this study was to evaluate the 2-year changes in the types of foods and beverages served during a community-based intervention design ed to achieve the Healthy Eating St and ards . STUDY DESIGN R and omized delayed treatment trial with an immediate ( 1-year baseline and 2-year intervention ) or delayed ( 2-year baseline and 1-year intervention ) group . SETTING / PARTICIPANTS Twenty ASPs serving 1,700 children ( aged 5 - 12 years ) were recruited , with baseline occurring spring 2013 , and outcome assessment occurring spring 2014 and 2015 . INTERVENTION The multistep intervention , Strategies To Enhance Practice for Healthy Eating , assisted ASP leaders/staff to serve foods/beverages that meet the nutrition st and ards . MAIN OUTCOME MEASURES The foods and beverages served for snack were observed directly . RESULTS Compared with non-intervention years , both the immediate and delayed groups increased the number of days/week that fruits/vegetables ( 0.6 vs 1.7 days/week and 0.6 vs 4.4 days/week , OR=3.80 , 95 % CI=1.45 , 9.95 ) and water ( 2.3 vs 3.7 days/week and 2.7 vs 4.8 days/week , OR=4.65 , 95 % CI=1.69 , 12.79 ) were served . Sugar-sweetened beverages were almost eliminated by post- assessment ( 1.2 vs 0.2 days/week and 3.2 vs 0.0 days/week , OR=0.05 , 95 % CI=0.02 , 0.13 ) . Only the immediate group decreased the number of days/week desserts were served ( 2.9 vs 0.6 days/week , OR=0.10 , 95 % CI=0.03 , 0.33 ) . Implementation barriers for the delayed group included once/month delivery sched Output:

In conclusion , there is evidence that , on average , lifestyle interventions can lead to small increases in children 's daily water consumption .

MS214112

***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: Periodontal disease ( PD ) in pregnancy is associated with an increased risk of adverse pregnancy outcomes including miscarriage and preterm birth . Evidence exists that periodontal disease treatment may reduce inflammatory mediators in gingival crevicular fluid ( GCF ) and the risk of inflammation-associated pregnancy complications . The aim was to determine if periodontal disease treatment during mid-pregnancy alters local inflammation in GCF and has beneficial effects on clinical dental parameters . Eighty pregnant women with clinical ly diagnosed PD were recruited from a r and omised controlled trial on the treatment of periodontal disease in pregnancy conducted in Perth , Australia . The treatment group underwent intensive PD treatment ( 20 - 28 weeks ' GA ) , while the control group underwent the same treatment postnatally . GCF was collected at 20 and 28 weeks ' gestation and concentrations of cytokines determined by multiplex assay : IL-1β , IL-6 , IL-8 , IL-10 , IL-12p70 , IL-17 , TNF-α and MCP-1 . Periodontal treatment significantly reduced the GCF levels of IL-1β , IL-10 , IL-12p70 and IL-6 at 28 weeks ' GA compared with controls , while levels of MCP-1 , IL-8 and TNF-α exhibited a significant gestational age-dependent increase , but no treatment response . Post-treatment clinical parameters improved with significant reductions in bleeding on probing , clinical attachment loss , and probing depth . No changes in pregnancy-related outcomes were observed , although the severity of periodontal disease was significantly associated with an increased risk of infants born small for gestational age . PD treatment in pregnancy reduces the levels of some inflammatory mediators in the GCF and improves dental parameters , with no overt effects on pregnancy outcome BACKGROUND AND OBJECTIVE A low- grade systemic inflammatory status originating from periodontal infection has been proposed to explain the association between periodontal disease and systemic conditions , including adverse obstetric outcomes . The aim of this study was to evaluate the effect of periodontal therapy during pregnancy on the gingival crevicular fluid and serum levels of six cytokines associated with periodontal disease and preterm birth . MATERIAL AND METHODS A sub sample of 60 women ( 18 - 35 years of age ) up to 20 gestational weeks , previously enrolled in a larger r and omized clinical trial , was recruited for the present study . Participants were r and omly allocated to receive either comprehensive nonsurgical periodontal therapy before 24 gestational weeks ( n = 30 , test group ) or only one appointment for supragingival calculus removal ( n = 30 , control group ) . Clinical data , and sample s of blood and gingival crevicular fluid , were collected at baseline , at 26 - 28 gestational weeks and 30 d after delivery . The levels of interleukin (IL)-1β , IL-6 , IL-8 , IL-10 , IL-12p70 and tumor necrosis factor-α were analyzed by flow cytometry . RESULTS After treatment , a major reduction in periodontal inflammation was observed in the test group , with bleeding on probing decreasing from 49.62 % of sites to 11.66 % of sites ( p < 0.001 ) . Periodontal therapy significantly reduced the levels of IL-1β and IL-8 in gingival crevicular fluid ( p < 0.001 ) . However , no significant effect of therapy was observed on serum cytokine levels . After delivery , the levels of IL-1β in the gingival crevicular fluid of the test group were significantly lower than were those in the control group ( p < 0.001 ) , but there were no significant differences between test and control groups regarding serum cytokine levels . CONCLUSION Although periodontal therapy during pregnancy successfully reduced periodontal inflammation and gingival crevicular fluid cytokine levels , it did not have a significant impact on serum biomarkers BACKGROUND Few studies have examined the potential effects of periodontal treatment during pregnancy on pregnancy outcomes , periodontal status , and inflammatory biomarkers . METHODS A r and omized , delayed-treatment , controlled pilot trial was conducted to evaluate the effects of second-trimester scaling and root planing and the use of a sonic toothbrush on the rate of preterm delivery ( < 37 weeks gestation ) . Secondary outcome measures included changes in periodontal status , levels of eight oral pathogens , levels of gingival crevicular fluid ( GCF ) interleukin-1beta ( IL-1beta ) , prostagl and in E(2 ) ( PGE(2 ) ) , 8-isoprostane ( 8-iso ) , and IL-6 , and serum levels of IL-6 , soluble intercellular adhesion molecule 1 ( sICAM1 ) , 8-isoprostane , soluble glycoprotein 130 ( sGP130 ) , IL-6 soluble receptor ( IL-6sr ) , and C-reactive protein ( CRP ) . Logistic regression models were used to test for effects of treatment on preterm delivery . Secondary outcomes were analyzed by analysis of covariance adjusting for subject baseline values . RESULTS Periodontal intervention result ed in a significantly decreased incidence odds ratio ( OR ) for preterm delivery ( OR = 0.26 ; 95 % confidence interval = 0.08 to 0.85 ) , adjusting for baseline periodontal status which was unbalanced after r and omization . Pregnancy without periodontal treatment was associated with significant increases in probing depths , plaque scores , GCF IL-1beta , and GCF IL-6 levels . Intervention result ed in significant improvements in clinical status ( attachment level , probing depth , plaque , gingivitis , and bleeding on probing scores ) and significant decreases in levels of Prevotella nigrescens and Prevotella intermedia , serum IL-6sr , and GCF IL-1beta . CONCLUSIONS Results from this pilot study ( 67 subjects ) provide further evidence supporting the potential benefits of periodontal treatment on pregnancy outcomes . Treatment was safe , improved periodontal health , and prevented periodontal disease progression . Preliminary data show a 3.8-fold reduction in the rate of preterm delivery , a decrease in periodontal pathogen load , and a decrease in both GCF IL-1beta and serum markers of IL-6 response . However , further studies will be needed to substantiate these early findings BACKGROUND Preterm low birth weight was reported to be related to periodontal infections that might influence the fetus-placenta complex . The aim of this study was to provide periodontal treatment for pregnant women and to evaluate if this treatment can interfere with pregnancy duration and weight of the newborn . METHODS The sample consisted of 450 pregnant women who were under prenatal care at a polyclinic in Três Corações , Brazil . Women with risk factors , such as systemic alterations ( ischemic cardiopathy , hypertension , tuberculosis , diabetes , cancer , anemia , seizure , psychopathology , urinary tract infection , sexually transmitted diseases , asthma , and human immunodeficiency virus ) , and /or users of alcohol , tobacco , and drugs were excluded from the study . Data related to age , socioeconomic level , race , marital status , number of previous pregnancies , and previous preterm delivery also were evaluated . Initially , the sample was divided into two groups : 122 healthy patients ( group 1 ) and 328 patients with periodontal disease ( group 2 ) . In group 2 , 266 patients underwent treatment and 62 patients dropped out . After mothers gave birth , pregnancy duration and the weight of all infants were analyzed and recorded . RESULTS There was no statistical difference between the healthy and treated groups . However , there was a difference in the non-treated group , with a 79 % incidence of preterm low birth weight . Educational level , previous preterm birth , and periodontal disease were related significantly to preterm delivery ( P < 0.001 ) . CONCLUSION Periodontal disease was related significantly to preterm low birth weight BACKGROUND Periodontitis has been associated with increased risk of adverse pregnancy outcomes and elevated C-reactive protein ( CRP ) concentrations in non-pregnant adults . We examined the relationship between periodontitis and CRP among women who provided dental radiographs and had blood collected during early pregnancy , excluding smokers and diabetic patients . METHODS From Project Viva , an ongoing cohort study , we measured plasma CRP in 35 subjects with periodontitis ( i.e. , at least one site with > or =3 mm of alveolar bone loss ) and a r and om sample of 66 periodontally healthy subjects matched on age and race/ethnicity . We performed linear regression analysis with log-transformed CRP levels as the outcome . RESULTS The mean ( + /- SE ) CRP level was 65 % higher ( 95 % confidence interval : -2 % , 180 % ; P = 0.06 ) in women with periodontitis ( 2.46 + /- 0.52 mg/l ) than in controls ( 1.49 + /- 0.22 mg/l ) , adjusting for factors related to CRP levels , including age , race/ethnicity , pre-pregnancy body mass index , alcohol intake , education , income , and gestational age at blood collection . CONCLUSIONS These findings suggest that periodontitis may increase CRP levels in pregnancy . CRP could potentially mediate the association of periodontitis with adverse pregnancy outcomes BACKGROUND The purpose of this study is to present the use of a non-r and omized experimental design with multiple controls , with emphasis on a historical control group , as an alternative method ologic re source for studies on the association between periodontal disease and prematurity/low birth weight . METHODS The sample consisted of 234 pregnant women : 54 in the Test Group ( treatment of periodontal disease ) ; 68 in Control Group I ( without periodontal disease ) ; and 112 in Control Group II ( historical control group , with untreated periodontal disease ) . The diagnosis of periodontal disease was established by means of a complete clinical examination , using measurements of probing depth , gingival recession , clinical attachment loss , and bleeding index . The women in the Test Group were treated for periodontitis and followed-up with periodontal support therapy throughout their pregnancies . After delivery , they were reevaluated regarding their periodontal condition , and information on the newborn 's birth weight was obtained . This was also done for Control Groups I and II . Descriptive analyses on the study variables were performed using the χ(2 ) and Fisher exact tests . Association measurements ( relative risk ) were obtained using a significance level of 5 % . RESULTS The frequency of low birth weight among the Test Group was similar to Control Group I and lower than Control Group II . CONCLUSION The results suggest that successful periodontal therapy in pregnant women suffering from periodontitis is a protective factor promoting the birth of children with normal weight BACKGROUND Recent studies have suggested that periodontal disease is a risk factor for preterm low birth weight ( PLBW ) . A r and omized controlled trial was undertaken to help further evaluate the proposed association between periodontal disease and PLBW . METHODS Four hundred pregnant women with periodontal disease , aged 18 to 35 , were enrolled while receiving prenatal care in Santiago , Chile . Women were r and omly assigned to either an experimental group ( n = 200 ) , which received periodontal treatment before 28 weeks of gestation or to a control group ( n = 200 ) which received periodontal treatment after delivery . Previous and current pregnancies and known risk factors were obtained from patient medical records and interviews . The primary outcome assessed was the delivery at less than 37 weeks of gestation or an infant weighing less than 2,500 g. RESULTS Of the 400 women enrolled , 49 were excluded from the analyses for different reasons . The incidence of PLBW in the treatment group was 1.84 % ( 3/163 ) and in the control group was 10.11 % ( 19/188 ) , ( odds ratio [ OR ] 5.49 , 95 % confidence interval [ CI ] 1.65 to 18.22 , P= 0.001 ) . Multivariate logistic regression analysis showed that periodontal disease was the strongest factor related to PLBW ( OR 4.70 , 95 % CI 1.29 to 17.13 ) . Other factors significantly associated with such deliveries were : previous PLBW ( OR 3.98 , 95 % CI 1.11 to 14.21 ) , less than 6 prenatal visits ( OR 3.70 , 95 % Cl 1.46 to 9.38 ) , and maternal low weight gain ( OR 3.42 , 95 % CI 1.16 to 10.03 ) . CONCLUSIONS Periodontal disease appears to be an independent risk factor for PLBW . Periodontal therapy significantly reduces the rates of PLBW in this population of women with periodontal disease AIM Determine whether periodontitis progression during pregnancy is associated with adverse birth outcomes . METHODS We used clinical data and birth outcomes from the Obstetrics and Periodontal Therapy Study , in which r and omly selected women received periodontal treatment before 21 weeks of gestation ( N=413 ) or after delivery ( 410 ) . Birth outcomes were available for 812 women and follow-up periodontal data for 722 , including 75 whose pregnancies ended < 37 weeks . Periodontitis progression was defined as > or=3 mm loss of clinical attachment . Birth outcomes were compared between non-progressing and progressing groups using the log rank and t tests , separately in all women and in un Output:

Intra-pregnancy nonsurgical periodontal therapy improved periodontal clinical parameters ( periodontal pocket depth , clinical attachment level , and bleeding on probing ) and reduced biomarker level from gingival crevicular fluid ( GCF ) , and some from blood serum ; however , it did not influence biomarker level from umbilical cord blood . Conclusions These results demonstrated that the intra-pregnancy nonsurgical periodontal therapy decreased periodontal inflammatory biomarker levels from gingival crevicular fluid and some from serum blood , with no influence on inflammatory biomarker level from cord blood , and it did not consistently reduce adverse gestational adverse outcome occurrence .

MS214113

***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: Women who exchange sex for money or other goods , that is , female sex workers , are at increased risk of experiencing physical and sexual violence from both paying and intimate partners . Exposure to violence can be exacerbated by alcohol use and HIV/STI risk . The purpose of this study is to examine the efficacy of a HIV/STI risk reduction and enhanced HIV/STI risk reduction intervention at decreasing paying and intimate partner violence against Mongolian women who exchange sex and engage in harmful alcohol use . Women are recruited and r and omized to either ( a ) four sessions of a relationship-based HIV/STI risk reduction intervention ( n = 49 ) , ( b ) the same HIV/STI risk reduction intervention plus two additional motivational interviewing sessions ( n = 58 ) , or ( c ) a four session control condition focused on wellness promotion ( n = 59 ) . All the respondents complete assessment s at baseline ( preintervention ) as well as at immediate posttest , 3 and 6 months postintervention . A multilevel logistic model finds that women who participated in the HIV/STI risk reduction group ( OR = 0.14 , p < .00 ) , HIV/STI risk reduction and motivational interview group ( OR = 0.46 , p = .02 ) , and wellness ( OR = 0.20 , p < .00 ) group reduced their exposure to physical and sexual violence in the past 90 days . No significant differences in effects are observed between conditions . This study demonstrates the efficacy of a relationship-based HIV/STI risk reduction intervention , a relationship-based HIV/STI risk reduction intervention combined with motivational interviewing , and a wellness promotion intervention in reducing intimate and paying partner violence against women who exchange sex in Mongolia . The findings have significant implication s for the impact of minimal intervention and the potential role of peer networks and social support in reducing women ’s experiences of violence in re source poor setting Objective We evaluate the effect of clinic-based support by HIV-positive Peer Mentors , in addition to st and ard clinic care , on maternal and infant well-being among Women Living with HIV ( WLH ) from pregnancy through the infant 's first year of life . Methods In a cluster r and omized controlled trial in KwaZulu-Natal , South Africa , eight clinics were r and omized for pregnant WLH to receive either : a St and ard Care condition ( SC ; 4 clinics ; n = 656 WLH ) ; or an Enhanced Intervention ( EI ; 4 clinics ; n = 544 WLH ) . WLH in the EI were invited to attend four antenatal and four postnatal meetings led by HIV-positive Peer Mentors , in addition to SC . WLH were recruited during pregnancy , and at least two post-birth assessment interviews were completed by 57 % of WLH at 1.5 , 6 or 12 months . EI 's effect was ascertained on 19 measures of maternal and infant well-being using r and om effects regressions to control for clinic clustering . A binomial test for correlated outcomes evaluated EI 's overall efficacy . Findings WLH attended an average of 4.1 sessions ( SD = 2.0 ) ; 13 % did not attend any sessions . Significant overall benefits were found in EI compared to SC using the binomial test . Secondarily , over time , WLH in the EI reported significantly fewer depressive symptoms and fewer underweight infants than WLH in the SC condition . EI WLH were significantly more likely to use one feeding method for six months and exclusively breastfeed their infants for at least 6 months . Conclusions WLH benefit by support from HIV-positive Peer Mentors , even though EI participation was partial , with incomplete follow-up rates from 6–12 months . Trial Registration Clinical Trials.gov Objective : To assess effects of a combined microfinance and training intervention on HIV risk behavior among young female participants in rural South Africa . Design : Secondary analysis of quantitative and qualitative data from a cluster r and omized trial , the Intervention with Microfinance for AIDS and Gender Equity study . Methods : Eight villages were pair-matched and r and omly allocated to receive the intervention . At baseline and after 2 years , HIV risk behavior was assessed among female participants aged 14–35 years . Their responses were compared with women of the same age and poverty group from control villages . Intervention effects were calculated using adjusted risk ratios employing village level summaries . Qualitative data collected during the study explored participants ' responses to the intervention including HIV risk behavior . Results : After 2 years of follow-up , when compared with controls , young participants had higher levels of HIV-related communication ( adjusted risk ratio 1.46 , 95 % confidence interval 1.01–2.12 ) , were more likely to have accessed voluntary counseling and testing ( adjusted risk ratio 1.64 , 95 % confidence interval 1.06–2.56 ) , and less likely to have had unprotected sex at last intercourse with a nonspousal partner ( adjusted risk ratio 0.76 , 95 % confidence interval 0.60–0.96 ) . Qualitative data suggest a greater acceptance of intrahousehold communication about HIV and sexuality . Although women noted challenges associated with acceptance of condoms by men , increased confidence and skills associated with participation in the intervention supported their introduction in sexual relationships . Conclusions : In addition to impacts on economic well being , women 's empowerment and intimate partner violence , interventions addressing the economic and social vulnerability of women may contribute to reductions in HIV risk behavior OBJECTIVES We examined the effect of a peer-delivered educational intervention , the Malawi Male Motivator intervention , on couples ' contraceptive uptake . We based the intervention design on the information-motivation-behavioral skills ( IMB ) model . METHODS In 2008 we recruited 400 men from Malawi 's Mangochi province who reported not using any method of contraception . We r and omized them into an intervention arm and a control arm , and administered surveys on contraceptive use at baseline and after the intervention . We also conducted in-depth interviews with a subset of intervention participants . RESULTS After the intervention , contraceptive use increased significantly within both arms ( P < .01 ) , and this increase was significantly greater in the intervention arm than it was in the control arm ( P < .01 ) . Quantitative and qualitative data indicated that increased ease and frequency of communication within couples were the only significant predictors of uptake ( P < .01 ) . CONCLUSIONS Our findings indicate that men facilitated contraceptive use for their partners . Although the IMB model does not fully explain our findings , our results show that the intervention 's content and its training in communication skills are essential mechanisms for successfully enabling men to help couples use a contraceptive Background Violence against female sex workers ( FSWs ) can impede HIV prevention efforts and contravenes their human rights . We developed a multi-layered violence intervention targeting policy makers , secondary stakeholders ( police , lawyers , media ) , and primary stakeholders ( FSWs ) , as part of wider HIV prevention programming involving > 60,000 FSWs in Karnataka state . This study examined if violence against FSWs is associated with reduced condom use and increased STI/HIV risk , and if addressing violence against FSWs within a large-scale HIV prevention program can reduce levels of violence against them . Methods FSWs were r and omly selected to participate in polling booth surveys ( PBS 2006 - 2008 ; short behavioural question naires administered anonymously ) and integrated behavioural-biological assessment s ( IBBAs 2005 - 2009 ; administered face-to-face ) . Results 3,852 FSWs participated in the IBBAs and 7,638 FSWs participated in the PBS . Overall , 11.0 % of FSWs in the IBBAs and 26.4 % of FSWs in the PBS reported being beaten or raped in the past year . FSWs who reported violence in the past year were significantly less likely to report condom use with clients ( zero unprotected sex acts in previous month , 55.4 % vs. 75.5 % , adjusted odds ratio ( AOR ) 0.4 , 95 % confidence interval ( CI ) 0.3 to 0.5 , p < 0.001 ) ; to have accessed the HIV intervention program ( ever contacted by peer educator , 84.9 % vs. 89.6 % , AOR 0.7 , 95 % CI 0.4 to 1.0 , p = 0.04 ) ; or to have ever visited the project sexual health clinic ( 59.0 % vs. 68.1 % , AOR 0.7 , 95 % CI 0.6 to 1.0 , p = 0.02 ) ; and were significantly more likely to be infected with gonorrhea ( 5.0 % vs. 2.6 % , AOR 1.9 , 95 % CI 1.1 to 3.3 , p = 0.02 ) . By the follow-up surveys , significant reductions were seen in the proportions of FSWs reporting violence compared with baseline ( IBBA 13.0 % vs. 9.0 % , AOR 0.7 , 95 % CI 0.5 to 0.9 p = 0.01 ; PBS 27.3 % vs. 18.9 % , crude OR 0.5 , 95 % CI 0.4 to 0.5 , p < 0.001 ) . Conclusions This program demonstrates that a structural approach to addressing violence can be effectively delivered at scale . Addressing violence against FSWs is important for the success of HIV prevention programs , and for protecting their basic human rights The aim of this study is to assess whether the Government of Kenya 's Cash Transfer for Orphans and Vulnerable Children ( Kenya CT-OVC ) can reduce the risk of HIV among young people by postponing sexual debut . The program provides an unconditional transfer of US$ 20 per month directly to the main caregiver in the household . An evaluation of the program was implemented in 2007–2009 in seven districts . Fourteen Locations were r and omly assigned to receive the program and fourteen were assigned to a control arm . A sample of households was enrolled in the evaluation in 2007 . We revisited these households in 2011 and collected information on sexual activity among individuals between 15–25 years of age . We used logistic regression , adjusted for the respondent 's age , sex and relationship to caregiver , the age , sex and schooling of the caregiver and whether or not the household lived in Nairobi at baseline , to compare rates of sexual debut among young people living in program households with those living in control households who had not yet entered the program . Our results , adjusted for these covariates , show that the program reduced the odds of sexual debut by 31 percent . There were no statistically significant effects on secondary outcomes of behavioral risk such as condom use , number of partners and transactional sex . Since the CT-OVC provides cash to the caregiver and not to the child , and there are no explicit conditions associated with receipt , these impacts are indirect , and may have been achieved by keeping young people in school . Our results suggest that large-scale national social cash transfer programs with poverty alleviation objectives may have potential positive spillover benefits in terms of reducing HIV risk among young people in Eastern and Southern Africa This article presents the results of a r and omized trial in South Africa of an adapted evidence -based Woman-Focused intervention on condom use with primary sex partners . The preliminary findings show that regardless of HIV status , condom negotiation was significantly associated with condom use at the 3- and 6-month follow-ups . By intervention group , significant intervention effects were found at 6-month follow-up for HIV-positive and HIV-unknown status women in the Woman-Focused intervention who were more likely than women in the St and ard intervention to report condom use with a primary male partner . Among HIV-positive women , those in the Woman-Focused group and those with greater sexual control were more likely to report condom use at the 6-month follow-up . The findings indicate that gender-based interventions for women may result in increased condom negotiation skills This cost-effectiveness study analyzes the cost per quality -adjusted life year ( QALY ) gained in a r and omized controlled trial that tested school support as a structural intervention to prevent HIV risk factors among Zimbabwe orphan girl adolescents . The intervention significantly reduced early marriage , increased years of schooling completed , and increased health-related quality of life . By reducing early marriage , the literature suggests the intervention reduced HIV infection . The intervention yielded an estimated US$ 1,472 in societal benefits and an estimated gain of 0.36 QALYs per orphan supported . It cost an estimated US$ 6/QALY gained , about 1 % of annual per capita income in Zimbabwe . That is well below the maximum price that the World Health Organization ( WHO ) Commission on Macroeconomics and Health recommends paying for health gains in low and middle income countries . About half the girls in the intervention condition were boarded when they reached high school . For non-boarders , the intervention ’s financial benefits exceeded its costs , yielding an estimated net cost savings of $ 502 per pupil . Without boarding , the intervention would yield net savings even if it were 34 % less effective in replication . Boarding was not cost-effective . It cost an additional $ 1,234 per girl boarded ( over the 3 years of the study , discounted to present value at a 3 % discount rate ) but had no effect on any of the outcome measures relative to girls in the treatment group who did not board . For girls who did not board , the average cost of approximately 3 years of school support was US$ 973 BACKGROUND Measurement of the global burden of disease with disability-adjusted life-years ( DALYs ) requires disability weights that quantify health losses for all non-fatal consequences of disease and injury Output:

The findings suggest that couple counselling for the prevention of vertical transmission ; gender empowerment , community mobilization , and female condom promotion for female sex workers ; exp and ed female condom distribution for the general population ; and post-exposure HIV prophylaxis for rape survivors are cost-effective HIV interventions . Cash transfers for schoolgirls and school support for orphan girls may also be cost-effective in generalized epidemic setting s. CONCLUSIONS There has been limited research to assess the cost-effectiveness of interventions that seek to address women 's needs and transform harmful gender norms . Our review identified several promising , cost-effective interventions that merit consideration as critical enablers in HIV investment approaches , as well as highlight that broader gender and development interventions can have positive HIV impacts .

MS214114

***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 purpose of this study was to test the effects of an education program in Tanzania design ed to reduce children 's risk of human immunodeficiency virus ( HIV ) infection and to improve their tolerance of and care for people with acquired immunodeficiency syndrome ( AIDS ) . METHODS A r and omized controlled community trial including baseline and 12-month follow-up surveys was employed . Public primary schools in the Arusha and Kilimanjaro regions of Tanzania were stratified according to location and r and omly assigned to intervention ( n = 6 ) or comparison ( n = 12 ) conditions . Of the 1063 sixth- grade students ( average age : 13.6 years ) who participated at baseline , 814 participated in the follow-up survey . RESULTS At follow-up , statistically significant effects favoring the intervention group were observed for exposure to AIDS information and communication , AIDS knowledge , attitudes toward people with AIDS , and subjective norms and behavioral intentions toward having sexual intercourse . A consistent positive but nonsignificant trend was seen for attitudes toward having sexual intercourse and for initiation of sexual intercourse during the previous year ( 7 % vs 17 % ) . CONCLUSIONS It is feasible and effective to train local teachers and health workers to provide HIV/AIDS education to Tanzanian primary school children Abstract Objective : To determine whether a theoretically based sex education programme for adolescents ( SHARE ) delivered by teachers reduced unsafe sexual intercourse compared with current practice . Design : Cluster r and omised trial with follow up two years after baseline ( six months after intervention ) . A process evaluation investigated the delivery of sex education and broader features of each school . Setting : Twenty five secondary schools in east Scotl and . Participants : 8430 pupils aged 13 - 15 years ; 7616 completed the baseline question naire and 5854 completed the two year follow up question naire . Intervention : SHARE programme ( intervention group ) versus existing sex education ( control programme ) . Main outcome measures : Self reported exposure to sexually transmitted disease , use of condoms and contraceptives at first and most recent sexual intercourse , and unwanted pregnancies . Results : When the intervention group was compared with the conventional sex education group in an intention to treat analysis there were no differences in sexual activity or sexual risk taking by the age of 16 years . However , those in the intervention group reported less regret of first sexual intercourse with most recent partner ( young men 9.9 % difference , 95 % confidence interval −18.7 to −1.0 ; young women 7.7 % difference , −16.6 to 1.2 ) . Pupils evaluated the intervention programme more positively , and their knowledge of sexual health improved . Lack of behavioural effect could not be linked to differential quality of delivery of intervention . Conclusions : Compared with conventional sex education this specially design ed intervention did not reduce sexual risk taking in adolescents Objective : To evaluate an HIV risk-reduction intervention among Namibian adolescents . Methods : A r and omized trial of a 14-session face-to-face intervention emphasizing abstinence and safer sexual practice s conducted among 515 youths ( median age 17 years and median grade 11 ) attending 10 secondary schools located in two districts in Namibia . Youths were r and omly assigned to the intervention or control condition at the level of the individual . HIV risk behaviours , intentions and perceptions were assessed at baseline , immediately post-intervention and at 6 and 12 months post-intervention . Results : Among all 515 youths who enrolled in the programme , rates of either abstinence or sex with a condom were not different between control and intervention youths at baseline or in the follow-up period . However , analyses conducted among the subset of youths who were sexually inexperienced at baseline ( n = 255 ) revealed that a higher percentage of intervention youths ( 17 % ) than control youths ( 9 % , P < 0.05 ) remained sexually inexperienced one year later . Moreover , in the immediate post-intervention period , among baseline virgins who subsequently initiated sex , intervention youths were more likely than control youths to use a condom ( 18 versus 10 % , P < 0.05 ) . Additional HIV-related risk behaviours ( failure to discuss previous HIV risk exposure with one 's sexual partner and alcohol use ) , intentions to use condoms , and perceptions of the ability to use condoms were positively affected by the intervention . Conclusions : There is evidence that the ‘ My Future is My Choice ’ ( MFMC ) intervention is reducing HIV risk behaviours among sexually inexperienced participants aged 15–18 . Related risk behaviours and perceptions are also positively impacted by the intervention PURPOSE To evaluate the effectiveness of peer education when compared to teacher-led curricula in AIDS prevention programs conducted in schools in Rome , Italy . METHODS Eighteen high schools were r and omly assigned to one of two prevention programs : one led by teachers and the other by peer leaders . A sample of students attending the last 2 years ( n = 1295 ) completed pre and post-intervention question naires . Changes in sexual behaviors , knowledge , prevention skills , risk perception and attitudes were first evaluated within each intervention group . Afterwards , changes in knowledge , prevention skills , risk perception , and attitudes total scale scores ( post-test scores minus pre-test scores ) were compared between the two groups , through linear regression models , in order to control for confounders , taking into account the within-school correlation in score changes . As for sexual behaviors , number of sexual partners and frequency of condom use in the 3 months before post-test were compared by intervention group through ordinal regression models , also taking into account behaviors reported before pre-test . RESULTS For both groups , we observed significant improvements in skills , knowledge , attitudes and risk perception . The peer-led group showed a 6.7 % ( 95 % C.I. 1.9 - 11.5 ) scores greater improvement in knowledge , compared to the teacher-led group . In neither group were improvements observed in condom use or number of sexual partners . CONCLUSIONS The only apparent benefit of the peer-led intervention , compared to that led by teachers , was a greater improvement in knowledge of HIV . Neither of the interventions induced changes in sexual behavior . However , the role of possible biases and method ological problems must be considered when interpreting these results PURPOSE To assess the effectiveness of a relatively unaltered version of a sexual risk reduction intervention previously shown to be effective among urban youth , " Original Focus on Kids " ( OFOK ) , compared with a version modified for West Virginia ( WVFOK ) and a control condition ( training in environmental conservation ) , in altering protective sexual behaviors and perceptions among rural , Appalachian youth . SUBJECTS Nine hundred ninety-nine youth aged 12 to 16 years from 12 rural counties in West Virginia . METHOD R and omized , controlled , longitudinal trial of a theory-based prevention intervention . Outcomes were self-reported sexual behaviors and perceptions assessed at baseline , 3 , 6 , and 9 months postintervention . RESULTS Both WVFOK and OFOK positively affected perceptions of abstinence but not behaviors . OFOK significantly enhanced some perceptions of condom use compared with both control youth and WVFOK youth , but again , not behaviors . CONCLUSIONS Overall , neither version was as effective as FOK had been in the original urban setting . The less altered version ( OFOK ) was more effective , especially with regard to condom-use perceptions , in this new population and cultural setting than the more culturally altered version ( WVFOK ) . In several of the implementation setting s , neither version was delivered as intended by the research ers because of logistic issues . Although many of these changes were seemingly minor , such deviations may have significant impact on intervention effect BACKGROUND Improvement of sex education in schools is a key part of the UK government 's strategy to reduce teenage pregnancy in Engl and . We examined the effectiveness of one form of peer-led sex education in a school-based r and omised trial of over 8000 pupils . METHODS 29 schools were r and omised to either peer-led sex education ( intervention ) or to continue their usual teacher-led sex education ( control ) . In intervention schools , peer educators aged 16 - 17 years delivered three sessions of sex education to 13 - 14 year-old pupils from the same schools . Primary outcome was unprotected ( without condom ) first heterosexual intercourse by age 16 years . Analysis was by intention to treat . FINDINGS By age 16 years , significantly fewer girls reported intercourse in the peer-led arm than in the control arm , but proportions were similar for boys . The proportions of pupils reporting unprotected first sex did not differ for girls ( 8.4 % intervention vs 8.3 % control ) or for boys ( 6.2 % vs 4.7 % ) . Stratified estimates of the difference between arms were -0.4 % ( 95 % CI -3.7 % to 2.8 % , p=0.79 ) for girls and -1.4 % ( -4.4 % to 1.6 % , p=0.36 ) for boys . At follow-up ( mean age 16.0 years [ SD 0.32 ] ) , girls in the intervention arm reported fewer unintended pregnancies , although the difference was borderline ( 2.3 % vs 3.3 % , p=0.07 ) . Girls and boys were more satisfied with peer-led than teacher-led sex education , but 57 % of girls and 32 % of boys wanted sex education in single-sex groups . INTERPRETATION Peer-led sex education was effective in some ways , but broader strategies are needed to improve young people 's sexual health . The role of single-sex sessions should be investigated further A computer- and Internet-based intervention was design ed to influence several variables related to the prevention of pregnancy , sexually transmitted diseases ( STDs ) , and human immunodeficiency virus ( HIV ) in rural adolescents . The intervention was guided by the extended parallel process model and was evaluated using a pretest – post-test control group design with r and om assignment at the school level . Three hundred and twenty-six tenth- grade males and females enrolled in two rural Appalachian public high schools completed the survey at both points in time . Results indicate the vast majority ( 88.5 % ) of students in the experimental school completed at least one activity ( M = 3.46 for those doing at least one activity ) . Further , both the overall program and all but one of the activities were rated positively by participants . Regarding the effects of the intervention , results indicate that students in the experimental school were less likely to initiate sexual activity and had greater general knowledge , greater condom negotiation self-efficacy , more favorable attitudes toward waiting to have sex , and greater situational self-efficacy than in the control school . In t and em , the results suggest that the computer-based programs may be a cost-effective and easily replicable means of providing teens with basic information and skills necessary to prevent pregnancy , STDs , and HIV This project assessed the impact of a school-based AIDS prevention program on student participation in sexual risk and protective behaviors such as use of condoms and use of condoms with foam and intention to participate in such behaviors . The paper focuses on students who became sexually active for the first time between the seventh and eighth grade ( " changers , " n = 312 ) . The school-based intervention was developed using social cognitive theory and the social influences model of behavior change . Using an experimental , longitudinal design , 15 high-risk school districts were divided r and omly into two treatment ( 10 districts ) and one control ( five districts ) conditions . Students in both treatment conditions received a 10-lesson classroom program in the seventh grade with a five-lesson booster in the eighth grade , while control students received basic AIDS education ( current practice in their districts ) in compliance with state m and ates . Results indicated classroom programs had an impact on certain protective behaviors and on frequency of sexual activity the past month . Post-intervention measures also indicated the program affected students ' intentions to perform specific protective behaviors This r and omized controlled trial tested the effects of a theory-based culture-sensitive HIV risk-reduction intervention among 496 inner-city African American adolescents ( mean age = 13 years ) and examined the generality of its effects as a function of the facilitator 's race and gender and the gender composition of the intervention group . Adolescents who received the HIV risk-reduction intervention expressed more favorable behavioral beliefs about condoms , greater self-efficacy , and stronger condom-use intentions postintervention than did those who received a control intervention on other health issues . Six-month follow-up data collected on 93 % of the adolescents revealed that those who received the HIV risk-reduction intervention reported less HIV risk-associated sexual behavior , including unprotected coitus , than did their counterparts in the control condition . Self-reported sexual behavior and changes in self-reported behavior were unrelated to scores on a st and ard measure of social desirability response bias . There was strong evidence for the generality of intervention effects . Moderator analyses testing eight specific interaction hypotheses and correlational analyses indicated that the effects of the HIV risk-reduction intervention did not vary as a function of the facilitator 's race or gender , participant 's gender , or the gender composition of the intervention group BACKGROUND The number of reported cases of acquired immune deficiency syndrome ( AIDS ) is increasing disproportionately among Blacks in the United States . The relatively high incidence of sexually transmitted diseases among Black adolescents suggest the need for AIDS prevention programs to reduce their risk of sexually transmitted human immunodeficiency virus ( HIV ) infection . METHODS Black male adolescents ( n = 157 ) were r and omly assigned to receive an AIDS risk reduction intervention aim ed at increasing AIDS-related knowledge and weakening problematic attitudes toward risky sexual behavior , or to receive a control intervention on career opportunities . RESULTS The adolescents who received the AIDS intervention subsequently had greater AIDS knowledge , less Output:

Data from 12 RCTs passed quality assessment criteria and provided evidence of positive changes in non-behavioural outcomes ( e.g. knowledge and self-efficacy ) . Intervention effects on behavioural outcomes , such as condom use , were generally limited and did not demonstrate a negative impact ( e.g. earlier sexual initiation ) . Beneficial effect on at least one , but never all behavioural outcomes assessed was reported by about half the studies , but this was sometimes limited to a participant subgroup .

MS214115

***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 Recent reports suggest that calcium-channel blockers may be harmful in patients with diabetes and hypertension . We previously reported that antihypertensive treatment with the calcium-channel blocker nitrendipine reduced the risk of cardiovascular events . In this post hoc analysis , we compared the outcome of treatment with nitrendipine in diabetic and nondiabetic patients . METHODS After stratification according to center , sex , and presence or absence of previous cardiovascular complications , 4695 patients ( age , > or = 60 years ) with systolic blood pressure of 160 to 219 mm Hg and diastolic pressure below 95 mm Hg were r and omly assigned to receive active treatment or placebo . Active treatment consisted of nitrendipine ( 10 to 40 mg per day ) with the possible addition or substitution of enalapril ( 5 to 20 mg per day ) or hydrochlorothiazide ( 12.5 to 25 mg per day ) or both , titrated to reduce the systolic blood pressure by at least 20 mm Hg and to less than 150 mm Hg . In the control group , matching placebo tablets were administered similarly . RESULTS At r and omization , 492 patients ( 10.5 percent ) had diabetes . After a median follow-up of two years , the systolic and diastolic blood pressures in the placebo and active-treatment groups differed by 8.6 and 3.9 mm Hg , respectively , among the diabetic patients . Among the 4203 patients without diabetes , systolic and diastolic pressures differed by 10.3 and 4.5 mm Hg , respectively , in the two groups . After adjustment for possible confounders , active treatment was found to have reduced overall mortality by 55 percent ( from 45.1 deaths per 1000 patients to 26.4 deaths per 1000 patients ) , mortality from cardiovascular disease by 76 percent , all cardiovascular events combined by 69 percent , fatal and nonfatal strokes by 73 percent , and all cardiac events combined by 63 percent in the group of patients with diabetes . Among the nondiabetic patients , active treatment decreased all cardiovascular events combined by 26 percent and fatal and nonfatal strokes by 38 percent . In the group of patients receiving active treatment , reductions in overall mortality , mortality from cardiovascular disease , and all cardiovascular events were significantly larger among the diabetic patients than among the nondiabetic patients ( P=0.04 , P=0.02 , and P=0.01 , respectively ) . CONCLUSIONS Nitrendipine-based antihypertensive therapy is particularly beneficial in older patients with diabetes and isolated systolic hypertension . Thus , our findings do not support the hypothesis that the use of long-acting calcium-channel blockers may be harmful in diabetic patients Current criteria for the diagnosis of diabetes c A1C $ 6.5 % . The test should be performed in a laboratory using a method that is NGSP certified and st and ardized to the Diabetes Control and Complications Trial ( DCCT ) assay ; or c fasting plasma glucose ( FPG ) $ 126 mg/dL ( 7.0 mmol/L ) . Fasting is defined as no caloric intake for at least 8 h ; or c 2-h plasma glucose $ 200 mg/dL ( 11.1 mmol/L ) during an oral glucose tolerance test ( OGTT ) . The test should be performed as described by the World Health Organization , using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved inwater ; or c in a patient with classic symptoms of hyperglycemia or hyperglycemic crisis , a r and om plasma glucose $ 200 mg/dL ( 11.1 mmol/L ) ; c in the absence of unequivocal hyperglycemia , result should be confirmed by repeat testing Background : Analyses of the risks of stroke were conducted for subjects with and without diabetes , participating in a r and omized , double‐blind , placebo‐controlled trial of a perindopril‐based blood pressure lowering regimen in 6105 people with prior stroke or transient ischaemic attack ( TIA ) , followed for a median of 3.9 years . Findings : Seven hundred and sixty‐one patients had diabetes at baseline . Diabetes increased the risk of recurrent stroke by 35 % ( 95 % CI 10–65 % ) principally through an effect on ischaemic stroke ( 1.53 , 95 % CI 1.23–1.90 ) . Active treatment reduced blood pressure by 9.5/4.6 mmHg in patients with diabetes and by 8.9/3.9 mmHg in patients without diabetes . The proportional risk reductions achieved for stroke in patients with diabetes , 38 % ( 95 % CI 8–58 % ) , and patients without diabetes , 28 % ( 95 % CI 16–39 % ) , were not significantly different ( p homogeneity = 0.5 ) . The absolute reduction in the risk of recurrent stroke in the patients with diabetes was equivalent to one stroke avoided among every 16 ( 95 % CI 9–111 ) patients treated for 5 years . Conclusions : Diabetes is an important risk factor for stroke in patients with established cerebrovascular disease . Treatment with the ACE inhibitor perindopril with discretionary use of the diuretic indapamide produced reductions in the risk of recurrent stroke in patients with diabetes that were at least as great as those achieved in patients without diabetes Aims Thiazolidinediones are insulin sensitizers , and are associated with fluid retention and increased risk of heart failure ( HF ) in people with type 2 diabetes . We assessed fatal and non-fatal HF events and their outcome , and identified HF predictors in the RECORD ( Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of glycaemia in Diabetes ) trial population . Methods and results In a multicentre , open-label study , we r and omized 4447 people with type 2 diabetes on metformin or sulfonylurea monotherapy with a mean HbA1c of 7.9 % to add-on rosiglitazone ( n = 2220 ) or to a combination of metformin and sulfonylurea ( n = 2227 ) and followed them over 5.5 years on average . Heart failure hospitalizations and deaths were adjudicated by a Clinical Endpoint Committee using pre-specified criteria . Independent predictors of HF events were identified out of a group of 30 pre-specified clinical , demographic , and biological variables . In the rosiglitazone group , the risk of HF death or hospitalization was doubled : HR = 2.10 ( 95 % CI , 1.35–3.27 ) : the excess HF event rate was 2.6 ( 1.1–4.1 ) per 1000 person-years . An excess in HF deaths was observed ( 10 vs. two ) , including four HF deaths as first HF events . By contrast , there was no increase in cardiovascular mortality or hospitalization ( HR = 0.99 , 95 % CI , 0.85–1.16 ) or in cardiovascular deaths ( 60 vs. 71 ) . Independent predictors of HF were rosiglitazone assignment , age , urinary albumin : creatinine ratio , body mass index , and systolic blood pressure at baseline . A history of previous cardiovascular disease was not predictive of HF . Duration of HF hospitalization and rate of HF re-hospitalization were similar in the two groups . Conclusion These findings confirm the increased risk of HF events in people treated with rosiglitazone and support the recommendation that this agent should not continue to be used in people developing symptomatic HF while using the medication . Close follow-up for the risk of HF should be offered to elderly people , people with markedly increased body mass index , people with microalbuminuria/proteinuria , and people with increased systolic blood pressure Summary Background Lowering LDL cholesterol with statin regimens reduces the risk of myocardial infa rct ion , ischaemic stroke , and the need for coronary revascularisation in people without kidney disease , but its effects in people with moderate-to-severe kidney disease are uncertain . The SHARP trial aim ed to assess the efficacy and safety of the combination of simvastatin plus ezetimibe in such patients . Methods This r and omised double-blind trial included 9270 patients with chronic kidney disease ( 3023 on dialysis and 6247 not ) with no known history of myocardial infa rct ion or coronary revascularisation . Patients were r and omly assigned to simvastatin 20 mg plus ezetimibe 10 mg daily versus matching placebo . The key prespecified outcome was first major atherosclerotic event ( non-fatal myocardial infa rct ion or coronary death , non-haemorrhagic stroke , or any arterial revascularisation procedure ) . All analyses were by intention to treat . This trial is registered at Clinical Trials.gov , NCT00125593 , and IS RCT N54137607 . Findings 4650 patients were assigned to receive simvastatin plus ezetimibe and 4620 to placebo . Allocation to simvastatin plus ezetimibe yielded an average LDL cholesterol difference of 0·85 mmol/L ( SE 0·02 ; with about two-thirds compliance ) during a median follow-up of 4·9 years and produced a 17 % proportional reduction in major atherosclerotic events ( 526 [ 11·3 % ] simvastatin plus ezetimibe vs 619 [ 13·4 % ] placebo ; rate ratio [ RR ] 0·83 , 95 % CI 0·74–0·94 ; log-rank p=0·0021 ) . Non-significantly fewer patients allocated to simvastatin plus ezetimibe had a non-fatal myocardial infa rct ion or died from coronary heart disease ( 213 [ 4·6 % ] vs 230 [ 5·0 % ] ; RR 0·92 , 95 % CI 0·76–1·11 ; p=0·37 ) and there were significant reductions in non-haemorrhagic stroke ( 131 [ 2·8 % ] vs 174 [ 3·8 % ] ; RR 0·75 , 95 % CI 0·60–0·94 ; p=0·01 ) and arterial revascularisation procedures ( 284 [ 6·1 % ] vs 352 [ 7·6 % ] ; RR 0·79 , 95 % CI 0·68–0·93 ; p=0·0036 ) . After weighting for subgroup-specific reductions in LDL cholesterol , there was no good evidence that the proportional effects on major atherosclerotic events differed from the summary rate ratio in any subgroup examined , and , in particular , they were similar in patients on dialysis and those who were not . The excess risk of myopathy was only two per 10 000 patients per year of treatment with this combination ( 9 [ 0·2 % ] vs 5 [ 0·1 % ] ) . There was no evidence of excess risks of hepatitis ( 21 [ 0·5 % ] vs 18 [ 0·4 % ] ) , gallstones ( 106 [ 2·3 % ] vs 106 [ 2·3 % ] ) , or cancer ( 438 [ 9·4 % ] vs 439 [ 9·5 % ] , p=0·89 ) and there was no significant excess of death from any non-vascular cause ( 668 [ 14·4 % ] vs 612 [ 13·2 % ] , p=0·13 ) . Interpretation Reduction of LDL cholesterol with simvastatin 20 mg plus ezetimibe 10 mg daily safely reduced the incidence of major atherosclerotic events in a wide range of patients with advanced chronic kidney disease . Funding Merck/Schering-Plough Pharmaceuticals ; Australian National Health and Medical Research Council ; British Heart Foundation ; UK Medical Research Council Aim To determine the safety and efficacy of nebivolol in elderly heart failure ( HF ) patients with renal dysfunction . Methods and results SENIORS recruited patients aged 70 years or older with symptomatic HF , irrespective of ejection fraction , and r and omized them to nebivolol or placebo . Patients ( n = 2112 ) were divided by tertile of estimated glomerular filtration rate ( eGFR ) . Mean age of patients was 76.1 years , 35 % of patients had an ejection fraction of > 35 % , and 37 % were women result ing in a unique cohort , far more representative of clinical practice than previous trials . eGFR was strongly associated with outcomes and nebivolol was similarly efficacious across eGFR tertiles . The primary outcome rate ( all-cause mortality or cardiovascular hospital admission ) and adjusted hazard ratio for nebivolol use in those with low eGFR was 40 % and 0.84 ( 95 % CI 0.67–1.07 ) , 31 % and 0.79 ( 0.60–1.04 ) in the middle tertile , and 29 % and 0.86 ( 0.65–1.14 ) in the highest eGFR tertile . There was no Output:

Several demonstrated no difference or an increased risk of adverse outcome among persons with DM and tight control of HTN as compared to usual control . Several demonstrated lack of benefit of statins among persons with end-stage renal disease . CONCLUSIONS There is limited evidence regarding the effects of multiple comorbidities on treatment outcomes . The majority of studies demonstrated no effect of a single comorbid condition on outcomes .

MS214116

***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 Taurolidin/Citrate ( TauroLock ™ ) , a lock solution with broad spectrum antimicrobial activity , may prevent bloodstream infection ( BSI ) due to coagulase-negative staphylococci ( CoNS or ' MRSE ' in case of methicillin-resistant isolates ) in pediatric cancer patients with a long term central venous access device ( CVAD , Port- or/Broviac-/Hickman-catheter type ) . Methods In a single center prospect i ve 48-months cohort study we compared all patients receiving anticancer chemotherapy from April 2003 to March 2005 ( group 1 , heparin lock with 200 IU/ml sterile normal saline 0.9 % ; Canusal ® Wockhardt UK Ltd , Wrexham , Wales ) and all patients from April 2005 to March 2007 ( group 2 ; taurolidine 1.35%/Sodium Citrate 4 % ; TauroLock ™ , Tauropharm , Waldbüttelbrunn , Germany ) . Results In group 1 ( heparin ) , 90 patients had 98 CVAD in use during the surveillance period . 14 of 30 ( 47 % ) BSI were ' primary Gram positive BSI due to CoNS ( n = 4 ) or MRSE ( n = 10 ) ' [ incidence density ( ID ) ; 2.30 per 1000 inpatient CVAD-utilization days].In group 2 ( TauroLock ™ ) , 89 patients had 95 CVAD in use during the surveillance period . 3 of 25 ( 12 % ) BSI were caused by CoNS . ( ID , 0.45 ) . The difference in the ID between the two groups was statistically significant ( P = 0.004 ) . Conclusion The use of Taurolidin/Citrate ( TauroLock ™ ) significantly reduced the number and incidence density of primary catheter-associated BSI due to CoNS and MRSE in pediatric cancer patients BACKGROUND Bacteremia is a major cause of morbidity in patients using intravascular catheters . Interdialytic locking with antibiotics decreases the incidence of bacteremia , but risks antibiotic resistance . Taurolidine is a nontoxic broad-spectrum antimicrobial agent that has not been associated with resistance . Preliminary evidence suggests that taurolidine-citrate locks decrease bacteremia , but cause flow problems in established catheters . STUDY DESIGN Double-blind r and omized controlled trial . INTERVENTION Interdialytic locking with taurolidine and citrate ( 1.35 % taurolidine and 4 % citrate ) compared with heparin ( 5,000 U/mL ) started at catheter insertion . SETTING & PARTICIPANTS 110 adult hemodialysis patients with tunneled cuffed intravascular catheters inserted at 3 centers in Northwest Engl and . OUTCOMES & MEASUREMENTS Primary end points were time to first bacteremia episode from any cause and time to first use of thrombolytic therapy . RESULTS There were 11 bacteremic episodes in the taurolidine-citrate group and 23 in the heparin group ( 1.4 and 2.4 episodes/1,000 patient-days , respectively ; P = 0.1 ) . There was no significant benefit of taurolidine-citrate versus heparin for time to first bacteremia ( hazard ratio , 0.66 ; 95 % CI , 0.2 - 1.6 : P = 0.4 ) . Taurolidine-citrate was associated with fewer infections caused by Gram-negative organisms than heparin ( 0.2 vs 1.1 infections/1,000 patient-days ; P = 0.02 ) ; however , there was no difference for Gram-positive organisms ( 1.1 vs 1.2 infections/1,000 patient-days ; P = 0.8 ) . There was a greater need for thrombolytic therapy in the taurolidine-citrate versus heparin group ( hazard ratio , 2.5 ; 95 % CI , 1.3 - 5.2 ; P = 0.008 ) . LIMITATIONS Small sample size . The study included bacteremia from all causes and was not specific for catheter-related bacteremia . CONCLUSIONS Taurolidine-citrate use did not decrease all-cause bacteremia and was associated with a greater need for thrombolytic treatment . There was a decrease in infections caused by Gram-negative organisms and a trend to a lower frequency of bacteremia , which warrants further study Background : Use of uncuffed catheters ( UCs ) in hemodialysis patients is common practice . An antibiotic lock has been recommended to prevent catheter-related bacteremia ( CRB ) , although insufficient data are available about the appropriate antimicrobial agent and dose with prolonged use of UCs . Methods : This open-label r and omized study was conducted to compare gentamicin/heparin ( group A ) and taurolidine/citrate ( group B ) , as catheter-lock solutions , in 119 chronic hemodialysis patients in whom a total of 150 UCs were placed . A well-matched historical control group ( heparin ) included 67 UCs in 58 patients ( group C ) . Results : CRB episodes developed in 6 and 8 patients in groups A and B , respectively , significantly fewer than in group C ( 20 patients ) . Cumulative CRB-free catheter survival at 90 days was 82 % for A and 78 % for B , which is significantly higher than the 26 % for C. Similar Gram-positive infection rates were found in all groups . The Gram-negative infection rate was significantly lower in B compared to C. No significant differences in thrombosis rates were observed between the groups . Conclusions : Gentamicin/heparin and taurolidine/citrate , used for locking UC , were similarly effective at preventing CRB and catheter thrombosis for up to 3 months , until a functional permanent vascular access became available . Both antimicrobial lock solutions were superior to heparin in CRB prevention with similar thrombosis rates BACKGROUND The use of haemodialysis catheters is complicated by catheter-related sepsis . Intraluminal colonization of the catheter with bacteria is important in the pathogenesis of catheter-related sepsis . The use of a catheter lock solution containing the antimicrobial taurolidine might prevent bacterial colonization , thereby reducing the incidence of catheter-related sepsis . METHODS In a r and omized prospect i ve trial , patients receiving a dialysis catheter were included and catheters were locked with either heparin or a citrate-taurolidine-containing solution . Blood cultures drawn from the catheter lumen were routinely taken every 2 weeks and at time of removal of the catheter to detect bacterial colonization . Catheter-related sepsis and exit-site infections were registered for both groups . RESULTS A total of 76 catheters were inserted in 58 patients . The incidence of catheter colonization progressed slowly over time with no differences between dialysis catheters filled with heparin or citrate-taurolidine-containing solution . The number of exit-site infections was also similar between both groups . In the heparin group , four cases of catheter-related sepsis occurred as opposed to no sepsis episodes in the patients with catheters locked with the citrate-taurolidine-containing solution ( P<0.5 ) . No side effects with the use of citrate-taurolidine catheter lock solution were noted . CONCLUSIONS This study shows that catheter filling with a solution containing the antimicrobial taurolidine may significantly reduce the incidence of catheter-related sepsis . Taurolidine appears to be effective and safe and does not carry the risk for side effects that have been reported for other antimicrobial lock solutions containing gentamicin or high concentrations of citrate BACKGROUND Intravenous catheters for haemodialysis increase the risk of sepsis . This study investigates the use of a taurolidine/citrate catheter-locking agent for patients receiving hospital-based haemodialysis , auditing the number and cost of infections before and after its introduction . METHODS The incidence and cost of treatment of catheter sepsis occurring in all patients receiving haemodialysis via a line were investigated over 6-month periods before and after introducing the taurolidine/citrate line-locking agent . RESULTS A reduction of 4.62 infections per 1000 catheter days , or 88.5 % , was shown after the introduction of the new line-locking agent . The total costs of line infections in the first 6 months were 52,500 euros , ( 41,000 pounds ) ; after the introduction of the taurolidine/citrate locks , these reduced to 33,300 euros , ( 26 , 000 pounds ) , a reduction of 19,200 euros ( 15,000 pounds ) . CONCLUSIONS The use of a taurolidine/citrate haemodialysis catheter-locking agent in our haemodialysis population has significantly reduced the line sepsis rate , with a positive impact on morbidity , mortality and cost BACKGROUND A catheter lock solution containing 1.35 % taurolidine and 4 % citrate could potentially disrupt bacterial surface adherence and consecutive biofilm production due to the anti-adherence properties of taurolidine and the anticlotting and chelator activities of both compounds . AIM To compare the impact on microbial catheter colonization and infectious complications of heparin and taurolidine citrate as central venous catheter ( CVC ) lock solutions in paediatric patients with haematological malignancies . METHODS Seventy-one patients aged 1.4 - 18 years were r and omized to two treatment groups using either heparin ( N = 36 ) or taurolidine citrate ( N = 35 ) . Infectious complications and clinical side-effects were prospect ively monitored and microbial colonization of catheters was assessed at the time of removal . FINDINGS There were two bloodstream infections in the taurolidine citrate group versus nine in the heparin group ( 0.3 vs 1.3 infections per 1000 catheter-days ; P = 0.03 ) . Fever of unknown origin and catheter occlusions were observed with a similar frequency in both groups . Microbial colonization was found in 25.4 % catheters . The time of no-lock use , but not the type of lock solution or time of observation , was a significant predictor of catheter colonization ( P = 0.004 ) . Colonization was not observed in CVCs used immediately with taurolidine citrate lock . Seven patients in the taurolidine citrate group ( 20 % ) experienced side-effects ( nausea , vomiting , abnormal taste sensations ) . CONCLUSION The use of taurolidine citrate lock solution was associated with a significant reduction in bloodstream infection in immunocompromised paediatric patients . Taurolidine citrate may prevent colonization of CVCs if used from the time of insertion , but not after a period of no-lock catheter use Output:

The results of this analysis indicated that taurolidine-citrate , compared to heparin , was more effective in preventing catheter-related infection ; therefore , it could be considered as a superior strategy . Nevertheless , compared to heparin-gentamicin combination , taurolidine-citrate is an inferior strategy because of its higher cost and lower infection prevention . CONCLUSION Compared to heparin , taurolidine-citrate is a superior option , but it is an inferior strategy compared to heparin-gentamicin combination .

MS214117

***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 neuromuscular training in reducing the rate of acute knee injury in adolescent female football players . Design Stratified cluster r and omised controlled trial with clubs as the unit of r and omisation . Setting 230 Swedish football clubs ( 121 in the intervention group , 109 in the control group ) were followed for one season ( 2009 , seven months ) . Participants 4564 players aged 12 - 17 years ( 2479 in the intervention group , 2085 in the control group ) completed the study . Intervention 15 minute neuromuscular warm-up programme ( targeting core stability , balance , and proper knee alignment ) to be carried out twice a week throughout the season . Main outcome measures The primary outcome was rate of anterior cruciate ligament injury ; secondary outcomes were rates of severe knee injury ( > 4 weeks ’ absence ) and any acute knee injury . Results Seven players ( 0.28 % ) in the intervention group , and 14 ( 0.67 % ) in the control group had an anterior cruciate ligament injury . By Cox regression analysis according to intention to treat , a 64 % reduction in the rate of anterior cruciate ligament injury was seen in the intervention group ( rate ratio 0.36 , 95 % confidence interval 0.15 to 0.85 ) . The absolute rate difference was −0.07 ( 95 % confidence interval −0.13 to 0.001 ) per 1000 playing hours in favour of the intervention group . No significant rate reductions were seen for secondary outcomes . Conclusions A neuromuscular warm-up programme significantly reduced the rate of anterior cruciate ligament injury in adolescent female football players . However , the absolute rate difference did not reach statistical significance , possibly owing to the small number of events . Trial registration Clinical trials NCT00894595 Background : Few authors have investigated the effectiveness of preventive intervention in European team h and ball . Purpose : The aim of the present study was to evaluate the effects of a prevention program on the incidence of injuries in female European team h and ball players . Study design : Prospect i ve controlled study . Methods : Ten female h and ball teams ( 134 players ) took part in the prevention program ( 1 . Information about injury mechanism , 2 . Balance-board exercises , 3 . Jump training ) while 10 other teams ( 142 players ) were instructed to train as usual . Over one season all injuries were documented weekly . Results : Ankle sprain was the most frequent diagnosis in both groups with 11 ankle sprains in the control group and 7 ankle sprains in the intervention group ( Odds ratio : 0.55 , 95 % confidence interval : 0.22–1.43 ) . The knee was the second frequent injury site . In the control group 5 of all knee injuries were anterior cruciate ligament ( ACL ) ruptures ( incidence : 0.21 per 1000 h ) in comparison with one in the intervention group ( incidence : 0.04 per 1000 h ) . Odds ratio was 0.17 with 95 % confidence interval of 0.02–1.5 . Conclusions : This study confirms that proprioceptive and neuromuscular training is appropriate for the prevention of knee and ankle injuries among female European team h and ball players Proprioceptive training has been shown to reduce the incidence of ankle sprains in different sports . It can also improve rehabilitation after anterior cruciate ligament ( ACL ) injuries whether treated operatively or nonoperatively . Since ACL injuries lead to long absence from sports and are one of the main causes of permanent sports disability , it is essential to try to prevent them . In a prospect i ve controlled study of 600 soccer players in 40 semiprofessional or amateur teams , we studied the possible preventive effect of a gradually increasing proprioceptive training on four different types of wobble-boards during three soccer seasons . Three hundred players were instructed to train 20 min per day with 5 different phases of increasing difficulty . The first phase consisted of balance training without any balance board ; phase 2 of training on a rectangular balance board ; phase 3 of training on a round board ; phase 4 of training on a combined round and rectangular board ; phase 5 of training on a so-called BABS board . A control group of 300 players from other , comparable teams trained “ normally ” and received no special balance training . Both groups were observed for three whole soccer seasons , and possible ACL lesions were diagnosed by clinical examination , KT-1000 measurements , magnetic resonance imaging or computed tomography , and arthroscopy . We found an incidence of 1.15 ACL injuries per team per year in the control group and 0.15 injuries per team per year in the proprioceptively trained group ( P<0.001 ) . Proprioceptive training can thus significantly reduce the incidence of ACL injuries in soccer players A set of exercises -- the " 11"--have been selected to prevent football injuries . The purpose of this cluster-r and omized controlled trial was to investigate the effect of the " 11 " on injury risk in female youth football . Teams were r and omized to an intervention ( n=59 teams , 1091 players ) or a control group ( n=54 teams , 1001 players ) . The intervention group was taught the " 11 , " exercises for core stability , lower extremity strength , neuromuscular control and agility , to be used as a 15-min warm-up program for football training over an 8-month season . A total of 396 players ( 20 % ) sustained 483 injuries . No difference was observed in the overall injury rate between the intervention ( 3.6 injuries/1000 h , confidence interval ( CI ) 3.2 - 4.1 ) and control group ( 3.7 , CI 3.2 - 4.1 ; RR=1.0 , CI 0.8 - 1.2 ; P=0.94 ) nor in the incidence for any type of injury . During the first 4 months of the season , the training program was used during 60 % of the football training sessions , but only 14 out of 58 intervention teams completed more than 20 prevention training sessions . In conclusion , we observed no effect of the injury prevention program on the injury rate , most likely because the compliance with the program was low OBJECTIVE To determine the numbers needed to treat ( NNT ) and relative risk reduction ( RRR ) associated with neuromuscular training programs aim ed at preventing noncontact anterior cruciate ligament ( ACL ) injuries in female athletes . DATA SOURCES We search ed PubMed , MEDLINE , SPORT Discus , CINAHL , and Web of Science from 1966 through 2005 using the terms knee , injury , anterior cruciate ligament , ACL , prevention , plyometric , and neuromuscular training . STUDY SELECTION Selected articles were from peer- review ed journals written in English that described original research studies comparing neuromuscular training programs with control programs to determine the number of noncontact ACL injuries per event exposure or hours of playing time . Five studies met the inclusion criteria and were independently rated by 3 review ers using the Physiotherapy Evidence Data base ( PEDro ) scale . Consensus PEDro scores ranged from 4 to 7 out of 10 . DATA EXTRACTION We used numbers of subjects , ACL injuries , and injury exposure rates to calculate NNT and RRR for each study . The NNT calculations from all studies were based on the number of players across 1 competitive season and were described as NNT benefit or NNT harm . DATA SYNTHESIS All 5 studies demonstrated a prophylactic effect due to the neuromuscular training programs . The pooled NNT estimates showed that 89 individuals ( 95 % confidence interval : 66 to 136 ) would need to participate in the prophylactic training program to prevent 1 ACL injury over the course of 1 competitive season . Pooled RRR was 70 % ( 95 % confidence interval : 54 % to 80 % ) among individuals who participated in the intervention program . One high- quality r and omized control trial and 4 medium- quality prospect i ve cohort studies showed mostly consistent findings . Thus , a Strength of Recommendation Taxonomy level of evidence of 1 with a grade B recommendation supports the use of neuromuscular training programs in the prevention of noncontact ACL injuries in female athletes BACKGROUND Studies have suggested that exercise programs can reduce the incidence of noncontact injuries of the anterior cruciate ligament in female athletes . We conducted a two-year prospect i ve study to assess the effects of a knee ligament injury prevention exercise program on the incidence of noncontact anterior cruciate ligament injuries in high-school female athletes . METHODS A prospect i ve cohort design was used to study high-school female athletes ( playing soccer , basketball , and volleyball ) from fifteen schools ( 112 teams ) for two consecutive seasons . The schools were divided into treatment and control groups . The treatment group participated in a plyometric-based exercise program twice a week throughout the season . Practice and game exposures and compliance with the exercise program were recorded on a weekly basis . Suspected noncontact anterior cruciate ligament injuries were confirmed on the basis of the history as well as at the time of surgery and /or with magnetic resonance imaging . RESULTS A total of 1439 athletes ( 862 in the control group and 577 in the treatment group ) were monitored . There were six confirmed noncontact anterior cruciate ligament injuries : three in the treatment group , and three in the control group . The incidence of noncontact anterior cruciate ligament injuries per 1000 exposures was 0.167 in the treatment group and 0.078 in the control group , yielding an odds ratio of 2.05 , which was not significant ( p > 0.05 ) . CONCLUSIONS Our results suggest that a twenty-minute plyometric-based exercise program that focuses on the mechanics of l and ing from a jump and deceleration when running performed twice a week throughout the season will not reduce the rate of noncontact anterior cruciate ligament injuries in high-school female athletes To assess the effect of a neuromuscular training program on the incidence of anterior cruciate ligament ( ACL ) injuries in female team h and ball athletes , a prospect i ve intervention study of female team h and ball athletes from divisions I , II , and III in Norway was conducted . The control season ( 1998 - 1999 ) included 60 teams ( 942 athletes ) , the first intervention season ( 1999 - 2000 ) included 58 teams ( 855 athletes ) , and the second intervention season ( 2000 - 2001 ) included 52 teams ( 850 athletes ) . For the intervention teams , a five-phase program ( duration , 15 minutes ) with three different balance exercises focusing on neuromuscular control and planting and l and ing skills was developed and introduced to the athletes in the autumn of 1999 and revised before the start of the season in 2000 . Each intervention team was instructed in the program and supplied with an instructional video , poster , six balance mats , and six wobble boards . Additionally , a physical therapist was assigned to each team for follow-up during the second intervention season . The number of ACL injuries during the three seasons and compliance with the program were assessed . Twenty-nine ACL injuries occurred during the control season , 23 during the first intervention season ( odds ratio [ OR ] , 0.87 [ 0.50 - 1.52 ] ; P = 0.62 ) , and 17 during the second intervention season ( OR , 0.64 [ 0.35 - 1.18 ] ; P = 0.15 ) . In the elite division , 13 injuries occurred during the control season , 6 during the first intervention season ( OR , 0.51 [ 0.19 - 1.35 ] ; P = 0.17 ) , and 5 during the second intervention season ( OR , 0.37 [ 0.13 - 1.05 ] ; P = 0.06 ) . For the entire cohort , no difference in injury rates was noted during the second intervention season between compliers and noncompliers ( OR , 0.52 [ 0.15 - 1.82 ] , P = 0.31 ) . In the elite division , the risk of injury was reduced among athletes who completed the ACL injury prevention program ( OR , 0.06 [ 0.01 - 0.54 ] , P = 0.01 ) compared with those who did not . The results demonstrate that it is possible to prevent ACL injuries with specific neuromuscular training Objective To investigate whether a neuromuscular training programme is effective in preventing non-contact leg injuries in female floorball players . Design Cluster r and omised controlled study . Setting 28 top level female floorball teams in Finl and . Participants 457 players ( mean age 24 years)—256 ( 14 teams ) in the intervention group and 201 ( 14 teams ) in the control group — followedup for one league season ( six months ) . Intervention A neuromuscular training programme to enhance players ’ motor skills and body control , as well as to activate and prepare their neuromuscular system for sports specific manoeuvres . Main outcome measure Acute non-contact injuries of the legs . Results During the season , 72 acute non-contact leg injuries occurred , 20 in the intervention group and 52 in the control group . The injury incidence per 1000 hours playing and practise in the intervention group was 0.65 ( 95 % confidence interval 0.37 to 1.13 ) and in the control group was 2.08 ( 1.58 to 2.72 ) . The risk of non-contact leg injury was 66 % lower ( adjusted incidence rate ratio 0.34 , 95 % confidence interval 0.20 to 0.57 ) in the intervention group . Conclusion A neuromuscular training programme was effective in preventing acute non Output:

The results of this systematic review and meta- analysis favor a protective effect of neuromuscular training programs on the risk of ACL rupture in female athletes . This protective effect is more pronounced in soccer players .

MS214118

***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 A r and omized controlled trial was performed to compare the short-term effects of alendronate ( ALN ) and ECT on pain and quality of life ( QOL ) in postmenopausal women with osteoporosis . Back pain and QOL [ Short-Form Health Survey ( SF-8 ) ] significantly improved at 1 , 3 , and 6 months in both groups , with greater improvements in the ALN group than in the ECT group . These results suggested that ALN reduced back pain and improved QOL more markedly than ECT in postmenopausal osteoporotic women with back pain . Introduction Intramuscular ECT is known to reduce pain via the central nervous system . A multicenter r and omized controlled trial was performed to compare the short-term effects of ALN and ECT on pain and QOL in postmenopausal women with osteoporosis . Methods One hundred and 94 postmenopausal osteoporotic women with back pain ( mean age 79.8 years , range 60–96 years ) were r and omly divided into two groups : the ALN group ( 35 mg weekly ) and the ECT group ( intramuscular 20 units a week ) . The duration of the study was 6 months . The trial was completed in 97 ( 100 % ) women of the ALN group and 96 ( 99.0 % ) women of the ECT group . Urinary levels of cross-linked N-terminal telopeptide of type I collagen ( NTX ) , serum alkaline phosphatase ( ALP ) , face scale score ( FSS , back pain ) , and SF-8 ( QOL ) were monitored . Results Urinary NTX levels significantly decreased at 3 months in the ALN group , but not in the ECT group . Serum ALP levels significantly decreased at 6 months in the both groups , with a greater reduction in the ALN group . The FSS and SF-8 significantly improved at 1 , 3 , and 6 months in both groups , with greater improvements in the ALN group than in the ECT group . Conclusions ALN suppressed bone turnover , reduced back pain , and improved QOL more markedly than ECT in postmenopausal osteoporotic women with back pain OBJECTIVE To evaluate the efficacy and safety of rhPTH ( 1 - 34 ) vs. elcatonin . METHODS Sixty patients with primary OP were r and omly divided into two groups according to the ratio of 3:1 . rhPTH ( 1 - 34 ) group ( PTH group ) was treated with subcutaneous injection of rhPTH ( 1 - 34 ) 20 μ g daily for 18 months , and the elcatonin group ( CT group ) was treated with intramuscular injection of elcatonin 20 U weekly for 12 months . Bone mineral density ( BMD ) of the lumbar spine 2 - 4 ( L2 - 4 ) and femoral neck , serum calcium and phosphorus , urinary calcium , serum bone specific alkaline phosphatase ( BSAP ) , and urinary c-terminal telopeptides of type I collagen/creatinine ( uCTX-I/Cr ) were tested at baseline , and 6 , 12 , and 18 months after treatment . RESULTS In PTH group , BMD of L2 - 4 at 6 , 12 , and 18 months , BDM of femoral neck at 18 month , BSAP at 6 and 12 months and uCTX- I/Cr at 6 , 12 and 18 months were all significantly raised . In CT group , BMD of L2 - 4 at 12 month and that of femoral neck at 12 and 18 months were significantly elevated , while BSAP was significantly decreased at 12 and 18 months , and no significant difference on CTX- I/Cr was observed . When BMD growth and growth rate between two groups were compared , PTH group had better improvement in L2 - 4 BMD and growth rate than CT group at 6 , 12 , and 18 months . BMD growth and growth rate of femoral neck at 12 month and its growth at 18 month in CT group were higher than in PTH group , but there was no significant difference between two groups regarding the growth rates at 18 month . Besides , there were no significant differences regarding the rates of adverse reactions between two groups . CONCLUSIONS rhPTH ( 1 - 34 ) , is safe and effective in the treatment of primary OP . It is superior to elcatonin in improving vertebral BMD at onset time , growth rate and growth range , but inferior to elcatonin at BMD of femoral neck The aim of this study was to compare the efficacy of elcatonin injections and oral nonsteroidal anti-inflammatory drugs ( NSAIDs ) for patients with osteoporosis who have acute lumbar pain after experiencing new vertebral compression fractures . Two hundred twenty-eight Japanese female patients ( mean age 77.3 years ) with acute lumbar pain from osteoporotic vertebral fractures were r and omly divided into two groups . Patients in one group were given an NSAID ( NSAIDs group ) and patients in the other group were given weekly intramuscular injections of 20 units of elcatonin ( elcatonin group ) . All patients underwent follow-up examinations up to 6 weeks from the start of the trial . Outcome measures were the level of functional impairment according to the Japan Question naire for Osteoporotic Pain ( JQ22 ) , the Rol and –Morris Disability Question naire ( RDQ ) , and a visual analog scale ( VAS ) of pain intensity . Statistical analyses focused on ( 1 ) the time course of pain and functional level using linear mixed effects models to analyze the longitudinal data and ( 2 ) the effectiveness of elcatonin injection with mean difference values and 95 % confidence intervals . Significant differences were seen over time between the initial values and the postintervention values ( 4 and 6 weeks ) in JQ22 , RDQ , and VAS scores ( effect size d > 0.4 ) in each group . The mean differences between the elcatonin group and the NSAIDs group in each measure at 4 and 6 weeks were −4.8 and −8.3 for the JQ22 , −1.3 and −2.6 for the RDQ , and −11.3 and −11.5 for the VAS , shifted to elcatonin . Once weekly elcatonin injection was more effective than NSAIDs for treating acute lumbar pain and improving mobility in Japanese women with osteoporotic vertebral fractures OBJECTIVE To evaluate three different therapeutic regimens for the prevention of osteoporosis in natural and surgical postmenopausal women who had been found to have rapid bone loss in analytical studies . METHODS A total of 104 naturally or surgically postmenopausal women were studied , and subsequently followed-up during 1 year for avoidance of the influence of seasonal variation on bone mass , a factor overlooked in several studies . They were r and omized into four groups of 26 patients each : the untreated control group ( mean age 50 + /- 5 years ) ; the hormonal replacement treatment ( HRT ) group ( mean age 48 + /- 6 years ) , which was treated for 24 days each month with transdermal 17 beta-estradiol , 50 mg/day , together with medroxiprogesterone , 10 mg during 12 days ; the calcium group ( mean age 50 + /- 4 years ) , which was treated with elemental calcium , 1 g/day ; and the calcitonin group ( mean age 50 + /- 5 years ) , which was treated for 10 days each month with eel calcitonin , 40 IU/day and with elemental calcium , 500 mg/day . Full-body bone densitometry , for measuring total body bone mineral content ( TB BMC ) , was carried out in all the women at baseline and 1 year . TB BMC was corrected for body weight by dividing its value by body weight ( TB BMC /W ) . RESULTS After 1 year TB BMC /W was lower in every group : -2.14 % ( P < 0.001 ) in the control group ; -0.14 % ( P = NS ) in the HRT group ( P < 0.05 vs. controls ) ; -0.18 % ( P = NS ) in the calcium group ( P < 0.05 vs. controls ) ; and -0.06 % ( P = NS ) in the calcitonin group ( P < 0.01 vs. controls ; P < 0.05 vs. calcium and HRT ) . CONCLUSIONS These findings show that all three treatments are effective in the prevention of postmenopausal loss of bone mass BACKGROUND Recombinant human parathyroid hormone ( 1 - 34 ) ( rhPTH ( 1 - 34 ) ) is the first agent in a unique class of anabolic therapies acting on the skeleton . The efficacy and safety of long-term administration of rhPTH ( 1 - 34 ) in Chinese postmenopausal women had not been evaluated . This study compared the clinical efficacy and safety of rhPTH ( 1 - 34 ) with elcatonin for treating postmenopausal women with osteoporosis in 11 urban areas of China . METHODS A total of 453 postmenopausal women with osteoporosis were enrolled in an 18-month , multi-center , r and omized , controlled study . They were r and omized to receive either rhPTH ( 1 - 34 ) 20 µg ( 200 U ) daily for 18 months , or elcatonin 20 U weekly for 12 months . Lumbar spine ( L1 - 4 ) and femoral neck bone mineral density ( BMD ) , fracture rate , back pain as well as biochemical markers of bone turnover were measured . Adverse events were recorded . RESULTS rhPTH ( 1 - 34 ) increased lumbar BMD significantly more than did elcatonin after 6 , 12 , and 18 months of treatment ( 4.3 % vs. 1.9 % , 6.8 % vs. 2.7 % , 9.5 % vs. 2.9 % , P < 0.01 ) . There was only a small but significant increase of femoral neck BMD after 18 months ( 2.6 % , P < 0.01 ) in rhPTH groups . There were larger increases in bone turnover markers in the rhPTH ( 1 - 34 ) group than those in the elcatonin group after 6 , 12 , and 18 months ( serum bone-specific alkaline phosphatase ( BSAP ) 93.7 % vs. -3.6 % ; 117.8 % vs. -4.1 % ; 49.2 % vs. -5.8 % , P < 0.01 ; urinary C-telopeptide/creatinine ( CTX/Cr ) 250.0 % vs. -29.5 % ; 330.0 % vs. -41.4 % , 273.0 % vs. -10.6 % , P < 0.01 ) . rhPTH ( 1 - 34 ) showed similar effect of pain relief as elcatonin . The incidence of clinical fractures was 5.36 % ( 6/112 ) in elcatonin group and 3.2 % ( 11/341 ) in rhPTH ( 1 - 34 ) group ( P = 0.303 ) . Both treatments were well tolerated . Hypercaluria ( 9.4 % ) and hypercalcemia ( 7.0 % ) in rhPTH ( 1 - 34 ) group were transient and caused no clinical symptoms . Pruritus ( 8.2 % vs. 2.7 % , P = 0.044 ) and redness of injection site ( 4.4 % vs. 0 , P = 0.024 ) were more frequent in rhPTH ( 1 - 34 ) . Nausea/vomiting ( 16.1 % vs. 6.2 % , P = 0.001 ) and hot flushes ( 7.1 % vs. 0.6 % , P < 0.001 ) were more common in elcatonin group . CONCLUSIONS rhPTH ( 1 - 34 ) was associated with greater increases in lumbar spine BMD and bone formation markers . It could increase femoral BMD after 18 months of treatment . rhPTH could improve back pain effectively . The results of the present study indicate that rhPTH ( 1 - 34 ) is an effective , safe agent in treating Chinese postmenopausal women with osteoporosis UNLABELLED In this longitudinal , prospect i ve , and population -based study ( n = 1044 ) , seven BTMs were assessed before and after trauma in 113 elderly women ( 85 with fractures ) . Markers were not altered in the immediate postfracture period but were clearly elevated during fracture repair . Recent fracture should thus be taken into account when markers are used in clinical practice . INTRODUCTION Fracture may influence the levels of bone turnover markers ( BTM ) and have implication s for their use in clinical practice . In this longitudinal , prospect i ve , and population -based study , we assessed prefracture levels of BTMs and compared them with postfracture levels of the same individuals immediately after fracture and during fracture repair . This is the first study in which the effect of fracture on bone markers has been evaluated with prefracture sample s available . MATERIAL S AND METHODS Serum and urine were collected at the emergency unit from 85 women ( 77.9 + /- 1.8 yr ) who sustained a fracture after low-energy trauma and 28 controls ( 77.8 + /- 2.0 yr ) with similar trauma but no fracture . All were participants of the Output:

Elcatonin therapies and non-elcatonin medications had comparable fracture rates and bone mineral density change . Conclusions Based on current evidence , C-E may be considered for treating postmenopausal osteoporosis because it benefits on pain relief and complications . Moreover , it shows comparable fracture rate and bone mineral density change as compared with anti-osteoporosis and calcium supplements .

MS214119

***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 study was to evaluate the effects of non-surgical treatment of periodontal disease during the second trimester of gestation on adverse pregnancy outcomes . Material and Methods Pregnant patients during the 1st and 2nd trimesters at antenatal care in a Public Health Center were divided into 2 groups : NIG – " no intervention " ( n=17 ) or IG- " intervention " ( n=16 ) . IG patients were su bmi tted to a non-surgical periodontal treatment performed by a single periodontist consisting of scaling and root planning ( SRP ) , professional prophylaxis ( PROPH ) and oral hygiene instruction ( OHI ) . NIG received PROPH and OHI during pregnancy and were referred for treatment after delivery . Periodontal evaluation was performed by a single trained examiner , blinded to periodontal treatment , according to probing depth ( PD ) , clinical attachment level ( CAL ) , plaque index ( PI ) and sulcular bleeding index ( SBI ) at baseline and 35 gestational weeks-28 days post-partum . Primary adverse pregnancy outcomes were preterm birth ( < 37 weeks ) , low birth weight ( < 2.5 kg ) , late abortion ( 14 - 24 weeks ) or abortion ( < 14 weeks ) . The results obtained were statistically evaluated according to OR , unpaired t test and paired t test at 5 % significance level . Results No significant differences were observed between groups at baseline examination . Periodontal treatment result ed in stabilization of CAL and PI ( p>0.05 ) at IG and worsening of all periodontal parameters at NIG ( p<0.0001 ) , except for PI . Significant differences in periodontal conditions of IG and NIG were observed at 2nd examination ( p<0.001 ) . The rate of adverse pregnancy outcomes was 47.05 % in NIG and 6.25 % in IG . Periodontal treatment during pregnancy was associated to a decreased risk of developing adverse pregnancy outcomes [ OR=13.50 ; CI : 1.47 - 123.45 ; p=0.02 ] . Conclusions Periodontal treatment during the second trimester of gestation contributes to decrease adverse pregnancy outcomes BACKGROUND One hypothesis to explain the association between periodontal disease ( PD ) preterm/low birth weight ( PT/LBW ) is that PT/LBW may be indirectly mediated through translocation of bacteria or bacterial products in the systemic circulation . Transient bacteremias occur in subjects with marginal periodontitis or with gingivitis , and it is possible that bacteria and their products may reach the placental membranes hematogenously and provide the inflammatory effect to induce preterm labor . The effect of gingivitis as a potential risk factor for PT/LBW has still not been studied . A r and omized controlled trial was undertaken to determine the effect of routine plaque control and scaling on the pregnancy outcomes in women with gingivitis . METHODS Eight hundred seventy ( 870 ) pregnant women with gingivitis , aged 18 to 42 , were enrolled while receiving prenatal care in Santiago , Chile . Women were r and omly assigned in a two-to-one fashion to either a treatment group ( N = 580 ) , receiving periodontal treatment before 28 weeks of gestation or to a control group ( N = 290 ) , receiving periodontal treatment after delivery . Periodontal therapy consisted of plaque control , scaling , and daily rinsing with 0.12 % clorhexidine . Maintenance therapy was provided every 2 to 3 weeks until delivery , and consisted of oral hygiene instruction and supragingival plaque removal by instrumentation , as needed . The primary outcomes assessed were delivery at less than 37 weeks of gestation or an infant weighing less than 2,500 g. RESULTS Of the 870 women enrolled , 36 women ( 27 in the treatment group and nine in the control group ) were excluded from the analyses for different reasons . The incidence of PT/LBW in the treatment group was 2.14 % ( 12/560 ) and in the control group , 6.71 % ( 19/283 ) ( odds ratio [ OR ] 3.26 ; 95 % confidence interval [ CI ] 1.56 to 6.83 ; P = 0.0009 ) . Multivariate logistic regression analysis showed that , after adjusting for several known risk factors for PT/LBW , women with gingivitis were at a higher risk of PT/LBW than women who received periodontal treatment ( OR 2.76 ; 95%CI 1.29 to 5.88 ; P = 0.008 ) . CONCLUSIONS Periodontal treatment significantly reduced the PT/LBW rate in this population of women with pregnancy-associated gingivitis . Within the limitions of this study , we conclude that gingivitis appears to be an independent risk factor for PT/LBW for this population Periodontal disease ( PD ) in pregnancy is associated with an increased risk of adverse pregnancy outcomes including miscarriage and preterm birth . Evidence exists that periodontal disease treatment may reduce inflammatory mediators in gingival crevicular fluid ( GCF ) and the risk of inflammation-associated pregnancy complications . The aim was to determine if periodontal disease treatment during mid-pregnancy alters local inflammation in GCF and has beneficial effects on clinical dental parameters . Eighty pregnant women with clinical ly diagnosed PD were recruited from a r and omised controlled trial on the treatment of periodontal disease in pregnancy conducted in Perth , Australia . The treatment group underwent intensive PD treatment ( 20 - 28 weeks ' GA ) , while the control group underwent the same treatment postnatally . GCF was collected at 20 and 28 weeks ' gestation and concentrations of cytokines determined by multiplex assay : IL-1β , IL-6 , IL-8 , IL-10 , IL-12p70 , IL-17 , TNF-α and MCP-1 . Periodontal treatment significantly reduced the GCF levels of IL-1β , IL-10 , IL-12p70 and IL-6 at 28 weeks ' GA compared with controls , while levels of MCP-1 , IL-8 and TNF-α exhibited a significant gestational age-dependent increase , but no treatment response . Post-treatment clinical parameters improved with significant reductions in bleeding on probing , clinical attachment loss , and probing depth . No changes in pregnancy-related outcomes were observed , although the severity of periodontal disease was significantly associated with an increased risk of infants born small for gestational age . PD treatment in pregnancy reduces the levels of some inflammatory mediators in the GCF and improves dental parameters , with no overt effects on pregnancy outcome Periodontitis has been associated with adverse pregnancy outcomes . Results from intervention studies are few and controversial . The present study assessed the effects of non-surgical periodontal treatment in the occurrence of adverse pregnancy outcomes . Two hundred forty-six eligible women were r and omly divided into two groups : periodontitis intervention ( n = 122 ; undergoing non-surgical treatment during gestation ) and periodontitis control ( n = 124 ; not treated during gestation ) . Univariate analysis was performed and estimates of relative risk were reported . Data from 225 women were analyzed . No differences for preterm birth ( p = 0.721 ) , low birth weight ( p = 0.198 ) , and preterm low birth weight ( p = 0.732 ) rates were observed . Relative risk estimates for preterm birth , low birth weight , and preterm low birth weight in the periodontitis intervention group were 0.915 ( 95 % CI 0.561–1.493 ) , 0.735 ( 95 % CI 0.459–1.179 ) , and 0.927 ( 0.601–1.431 ) , respectively . Non-surgical periodontal treatment during the second semester of gestation did not reduce the risk for preterm birth , low birth weight , and preterm low birth weight Considering the high prevalence of preterm birth ( PTB ) and low birth weight ( LBW ) and their complications as well as the role played by periodontal disease in their incidence and the lack of any report of periodontal therapy on these problems in Iran , the goal of the present research was to determine the effects of periodontal treatment on PLBW incidence among women with moderate or advanced periodontitis who were referred to Javaheri hospital ( 2004 - 2005 ) . This clinical trial research was conducted on 30 pregnant women age ranging from 18 - 35 years old , with moderate or advanced periodontitis . Fifteen subjects r and omly underwent the first phase of periodontal treatment including scaling , root planning and the use of 0.2 % chlorhexidine mouth rinse for one week . None of these steps were taken for the controls . After necessary follow ups , the effect of periodontal treatment on birth term and birth weight were analyzed statistically . This research was conducted on 30 subjects , 15 controls and 15 cases in study group . In the control group , the observed rate of PLBW was 26.7 % whereas among periodontally treated group , phase I , PLBW infant was not observed ( P < 0.05 ) . Infants birth weight were ( 3059.3 - 389.7 ) gms in study group and ( 3371 - 394.2 ) gms in the control group and respectively ( P < 0.05 ) . Periodontal therapy , phase I , results in a reduction in PLBW incidence rate . Therefore , the application of such a simple method among periodontally diseased pregnant women is recommended BACKGROUND The purpose of the present study is to investigate the potential link between maternal periodontitis and pregnancy outcomes , including preterm birth ( < 37 weeks ) and low birth weight ( < 2,500 g ) . METHODS Ninety nine pregnant females with mild/moderate periodontitis were r and omly allocated to a control ( n = 50 ) or test ( n = 49 ) group . Test group participants received intrapregnancy non-surgical periodontal treatment , whereas this was deferred until after delivery for controls . Demographic and baseline clinical data were obtained for all participants at initial assessment pretreatment . Clinical data were rerecorded for test participants at review 8 weeks after treatment . Birth outcomes were completed at delivery by midwives who also collected cord blood sample s when possible ; the latter were analyzed to determine the presence/levels of cytokines interleukin (IL)-1β , IL-6 , and IL-8 . All data were analyzed on an intention-to-treat basis using appropriate statistical tests . RESULTS R and om allocation of participants result ed in well-balanced control and test groups . All test group participants and all but one control participant gave birth to a live infant . No significant differences were detected between control and test groups with regard to birth outcome measures of birth weight and gestational age or in relation to cytokine prevalence/levels . CONCLUSION Intrapregnancy non-surgical periodontal treatment , completed at 20 to 24 weeks , did not reduce the risk of preterm , low-birth-weight delivery in this population BACKGROUND Few studies have examined the potential effects of periodontal treatment during pregnancy on pregnancy outcomes , periodontal status , and inflammatory biomarkers . METHODS A r and omized , delayed-treatment , controlled pilot trial was conducted to evaluate the effects of second-trimester scaling and root planing and the use of a sonic toothbrush on the rate of preterm delivery ( < 37 weeks gestation ) . Secondary outcome measures included changes in periodontal status , levels of eight oral pathogens , levels of gingival crevicular fluid ( GCF ) interleukin-1beta ( IL-1beta ) , prostagl and in E(2 ) ( PGE(2 ) ) , 8-isoprostane ( 8-iso ) , and IL-6 , and serum levels of IL-6 , soluble intercellular adhesion molecule 1 ( sICAM1 ) , 8-isoprostane , soluble glycoprotein 130 ( sGP130 ) , IL-6 soluble receptor ( IL-6sr ) , and C-reactive protein ( CRP ) . Logistic regression models were used to test for effects of treatment on preterm delivery . Secondary outcomes were analyzed by analysis of covariance adjusting for subject baseline values . RESULTS Periodontal intervention result ed in a significantly decreased incidence odds ratio ( OR ) for preterm delivery ( OR = 0.26 ; 95 % confidence interval = 0.08 to 0.85 ) , adjusting for baseline periodontal status which was unbalanced after r and omization . Pregnancy without periodontal treatment was associated with significant increases in probing depths , plaque scores , GCF IL-1beta , and GCF IL-6 levels . Intervention result ed in significant improvements in clinical status ( attachment level , probing depth , plaque , gingivitis , and bleeding on probing scores ) and significant decreases in levels of Prevotella nigrescens and Prevotella intermedia , serum IL-6sr , and GCF IL-1beta . CONCLUSIONS Results from this pilot study ( 67 subjects ) provide further evidence supporting the potential benefits of periodontal treatment on pregnancy outcomes . Treatment was safe , improved periodontal health , and prevented periodontal disease progression . Preliminary data show a 3.8-fold reduction in the rate of preterm delivery , a decrease in periodontal pathogen load , and a decrease in both GCF IL-1beta and serum markers of IL-6 response . However , further studies will be needed to substantiate these early findings BACKGROUND A recent clinical trial ( Obstetrics and Periodontal Therapy [ OPT ] Study ) demonstrated that periodontal therapy during pregn Output:

Conclusion : With best possible evidence , it can be inferred that nonsurgical periodontal therapy is safe during pregnancy .

MS214120

***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: Various studies have shown biostimulation effects of laser irradiation by producing metabolic changes within the cells . Little is known about the biological effect of laser irradiation on the oral tissues . Among the many physiological effects , it is important to recognize that low-level laser therapy ( LLLT ) may affect release of growth factors from fibroblasts . Therefore , the aim of the present study was to determine whether the laser irradiation can enhance the release of basic fibroblast growth factor ( bFGF ) , insulin-like growth factor-1 ( IGF-1 ) , and receptor of IGF-1 ( IGFBP3 ) from human gingival fibroblasts ( HGF ) . The number of all sample s in the study were 30 , and the sample s were r and omly divided into three equal groups ; In the first group ( single dose group ) , HGF were irradiated with laser energy of 685 nm , for 140 s , 2 J/cm2 for one time , and in the second group , energy at the same dose was applied for two consecutive days ( double dose group ) . The third group served as nonirradiated control group . Proliferation , viability , and bFGF , IGF-1 , IGFBP3 analysis of control and irradiated cultures were compared with each other . Both of the irradiated groups revealed higher proliferation and viability in comparison to the control group . Comparison of the single-dose group with the control group revealed statistically significant increases in bFGF ( p < 0.01 ) and IGF-1 ( p < 0.01 ) , but IGFBP3 increased insignificantly ( p > 0.05 ) . When the double dose group was compared with the control group , significant increases were determined in all of the parameters ( p < 0.01 ) . In the comparison of the differences between the two irradiated groups ( one dose and two doses ) , none of the parameters displayed any statistically significant difference ( p > 0.05 ) . In both of the laser groups , LLLT increased the cell proliferation and cell viability . The results of this study showed that LLLT increased the proliferation of HGF cells and release of bFGF , IGF-1 , and IGFBP3 from these cells . LLLT may play an important role in periodontal wound healing and regeneration by enhancing the production of the growth factors Evidence -based practice involves the use of evidence from systematic review s and r and omised controlled trials , but the extent of this evidence in physiotherapy has not previously been surveyed . The aim of this survey is to describe the quantity and quality of r and omised controlled trials and the quantity of systematic review s relevant to physiotherapy . The Physiotherapy Evidence Data base ( PEDro ) was search ed . The quality of trials was assessed with the PEDro scale . The search identified a total of 2,376 r and omised controlled trials and 332 systematic review s. The first trial was published in 1955 and the first review was published in 1982 . Since that time , the number of trials and review s has grown exponentially . The mean PEDro quality score has increased from 2.8 in trials published between 1955 and 1959 to 5.0 for trials published between 1995 and 1999 . There is a substantial body of evidence about the effects of physiotherapy . However , there remains scope for improvements in the quality of the conduct and reporting of clinical trials Objective : To compare the long-term efficacy of pneumatic compression and low-level laser therapies in the management of postmastectomy lymphoedema . Design : R and omized controlled trial . Setting : Department of Physical Medicine and Rehabilitation of Cukurova University , Turkey . Subjects : Forty-seven patients with postmastectomy lymphoedema were enrolled in the study . Interventions : Patients were r and omly allocated to pneumatic compression ( group I , n=24 ) and low-level laser ( group II , n=23 ) groups . Group I received 2 hours of compression therapy and group II received 20 minutes of laser therapy for four weeks . All patients were advised to perform daily limb exercises . Main measures : Demographic features , difference between sum of the circumferences of affected and unaffected limbs ( ▵ C ) , pain with visual analogue scale and grip strength were recorded . Results : Mean age of the patients was 48.3 ( 10.4 ) years . ▵ C decreased significantly at one , three and six months within both groups , and the decrease was still significant at month 12 only in group II ( P = 0.004 ) . Improvement of group II was greater than that of group I post treatment ( P = 0.04 ) and at month 12 after 12 months ( P = 0.02 ) . Pain was significantly reduced in group I only at posttreatment evaluation , whereas in group II it was significant post treatment and at follow-up visits . No significant difference was detected in pain scores between the two groups . Grip strength was improved in both groups , but the differences between groups were not significant . Conclusions : Patients in both groups improved after the interventions . Group II had better long-term results than group I. Low-level laser might be a useful modality in the treatment of postmastectomy lymphoedema The current study describes the results of a double blind , placebo‐controlled , r and omized , single crossover trial of the treatment of patients with postmastectomy lymphedema ( PML ) with low‐level laser therapy ( LLLT ) Abstract Background and Objective : As Light Emitting Diode ( LED ) devices are commercially introduced as an alternative for Low Level Laser ( LLL ) Therapy , the ability of LED in influencing wound healing processes at cellular level was examined . Study Design / Material s and Methods : Cultured fibroblasts were treated in a controlled , r and omized manner , during three consecutive days , either with an infrared LLL or with a LED light source emitting several wavelengths ( 950 nm , 660 nm and 570 nm ) and respective power outputs . Treatment duration varied in relation to varying surface energy densities ( radiant exposures ) . Results : Statistical analysis revealed a higher rate of proliferation ( p ≤ 0.001 ) in all irradiated cultures in comparison with the controls . Green light yielded a significantly higher number of cells , than red ( p ≤ 0.001 ) and infrared LED light ( p ≤ 0.001 ) and than the cultures irradiated with the LLL ( p ≤ 0.001 ) ; the red probe provided a higher increase ( p ≤ 0.001 ) than the infrared LED probe and than the LLL source . Conclusion : LED and LLL irradiation result ed in an increased fibroblast proliferation in vitro . This study therefore postulates possible stimulatory effects on wound healing in vivo at the applied dosimetric parameters The aim of this paper was to study the effects of low-level laser therapy ( LLLT ) in the treatment of postmastectomy lymphedema . Eleven women with unilateral postmastectomy lymphedema were enrolled in a double-blind controlled trial . Patients were r and omly assigned to laser and sham groups and received laser or placebo irradiation ( Ga – As laser device with a wavelength of 890 nm and fluence of 1.5 J/cm2 ) over the arm and axillary areas . Changes in patients ’ limb circumference , pain score , range of motion , heaviness of the affected limb , and desire to continue the treatment were measured before the treatment and at follow-up sessions ( weeks 3 , 9 , 12 , 18 , and 22 ) and were compared to pretreatment values . Results showed that of the 11 enrolled patients , eight completed the treatment sessions . Reduction in limb circumference was detected in both groups , although it was more pronounced in the laser group up to the end of 22nd week . Desire to continue treatment at each session and baseline score in the laser group was greater than in the sham group in all sessions . Pain reduction in the laser group was more than in the sham group except for the weeks 3 and 9 . No substantial differences were seen in other two parameters between the two treatment groups . In conclusion , despite our encouraging results , further studies of the effects of LLLT in management of postmastectomy lymphedema should be undertaken to determine the optimal physiological and physical parameters to obtain the most effective clinical response Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists PURPOSE / OBJECTIVES To examine the impact of advanced practice nurse (APN)-administered low-level laser therapy ( LLLT ) as both a st and -alone and complementary treatment for arm volume , symptoms , and quality of life ( QOL ) in women with breast cancer-related lymphedema . DESIGN A three-group , pilot , r and omized clinical trial . SETTING A private rehabilitation practice in the southeastern United States . SAMPLE 46 breast cancer survivors with treatment-related lymphedema . METHODS Patients were screened for eligibility and then r and omized to either manual lymphatic drainage ( MLD ) for 40 minutes , LLLT for 20 minutes , or 20 minutes of MLD followed by 20 minutes of LLLT . Compression b and aging was applied after each treatment . Data were collected pretreatment , daily , weekly , and at the end of treatment . MAIN RESEARCH VARIABLES Independent variables consisted of three types of APN-administered lymphedema treatment . Outcome variables included limb volume , extracellular fluid , psychological and physical symptoms , and QOL . FINDINGS No statistically significant between-group differences were found in volume reduction ; however , all groups had clinical ly and statistically significant reduction in volume . No group differences were noted in psychological and physical symptoms or QOL ; however , treatment-related improvements were noted in symptom burden within all groups . Skin improvement was noted in each group that received LLLT . CONCLUSIONS LLLT with b and aging may offer a time-saving therapeutic option to conventional MLD . Alternatively , compression b and aging alone could account for the demonstrated volume reduction . IMPLICATION S FOR NURSING APNs can effectively treat lymphedema . APNs in private healthcare practice s can serve as valuable research collaborators . KNOWLEDGE TRANSLATION Lasers may provide effective , less burdensome treatment for lymphedema . APNs with lymphedema certification can effectively treat this patient population with the use of LLLT . In addition , bioelectrical impedance and tape measurements can be used to assess lymphedema Muscle regeneration is a complex phenomenon , involving replacement of damaged fibers by new muscle fibers . During this process , there is a tendency to form scar tissue or fibrosis by deposition of collagen that could be detrimental to muscle function . New therapies that could regulate fibrosis and favor muscle regeneration would be important for physical therapy . Low-level laser therapy ( LLLT ) has been studied for clinical treatment of skeletal muscle injuries and disorders , even though the molecular and cellular mechanisms have not yet been clarified . The aim of this study was to evaluate the effects of LLLT on molecular markers involved in muscle fibrosis and regeneration after cryolesion of the tibialis anterior ( TA ) muscle in rats . Sixty Wistar rats were r and omly divided into three groups : control , injured TA muscle without LLLT , injured TA muscle treated with LLLT . The injured region was irradiated daily for four consecutive days , starting immediately after the lesion using an AlGaAs laser ( 808 nm , 30 mW , 180 J/cm2 ; 3.8 W/cm2 , 1.4 J ) . The animals were sacrificed on the fourth day after injury . LLLT significantly reduced the lesion percentage area in the injured muscle ( p < 0.05 ) , increased mRNA levels of the transcription factors MyoD and myogenin ( p < 0.01 ) and the pro-angiogenic vascular endothelial growth factor ( p < 0.01 ) . Moreover , LLLT decreased the expression of the profibrotic transforming growth factor TGF-β mRNA ( p < 0.01 ) and reduced type I collagen deposition ( p < 0.01 ) . These results suggest that LLLT could be an effective therapeutic approach for promoting skeletal muscle regeneration while preventing tissue fibrosis after muscle injury Secondary prevention involves monitoring and screening to prevent negative sequelae from chronic diseases such as cancer . Breast cancer treatment sequelae , such as lymphedema , may occur early or late and often negatively affect function . Secondary prevention through prospect i ve physical therapy surveillance aids in early identification and treatment of breast cancer – related lymphedema ( BCRL ) . Early intervention may reduce the need for intensive rehabilitation and may be cost saving . This perspective article compares a prospect i ve surveillance model with a traditional model of impairment-based care and exam Output:

Conclusions Based upon the current systematic review , LLLT ( PBM ) may be considered an effective treatment approach for women with BCRL .

MS214121

***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: R and omized clinical trials have identified a population of acute medically ill patients who remain at risk for venous thromboembolism ( VTE ) beyond the st and ard duration of therapy and hospital discharge . The aim of the APEX study is to determine whether extended administration of oral betrixaban ( 35 - 42 days ) is superior to a st and ard short course of prophylaxis with subcutaneous enoxaparin ( 10 ± 4 days followed by placebo ) in patients with known risk factors for post-discharge VTE . Patients initially are r and omized to receive either betrixaban or enoxaparin ( and matching placebo ) in a double dummy design . Following a st and ard duration period of enoxaparin treatment ( with placebo tablets ) or betrixaban ( with placebo injections ) , patients receive only betrixaban ( or alternative matching placebo ) . Patients are considered for enrollment if they are older than 40 years , have a specified medical illness , and restricted mobility . They must also meet the APEX criteria for increased VTE risk ( aged ≥75 years , baseline D-Dimer ≥2 × upper the limit of " normal " , or 2 additional ancillary risk factors for VTE ) . The primary efficacy end point is the composite of asymptomatic proximal deep venous thrombosis , symptomatic deep venous thrombosis , non-fatal ( pulmonary embolus ) pulmonary embolism , or VTE-related death through day 35 . The primary safety outcome is the occurrence of major bleeding . We hypothesize that extended duration betrixaban VTE prophylaxis will be safe and more effective than st and ard short duration enoxaparin in preventing VTE in acute medically ill patients with known risk factors for post hospital discharge VTE Background Venous thromboembolism comprising pulmonary embolism and deep vein thrombosis is a common condition with an incidence of approximately 1 per 1,000 per annum causing both mortality and serious morbidity . The principal aim of treatment of a venous thromboembolism with heparin and warfarin is to prevent extension or recurrence of clot . However , the recurrence rate following a deep vein thrombosis remains approximately 10 % per annum following treatment cessation irrespective of the duration of anticoagulation therapy . Patients with raised D-dimer levels after discontinuing oral anticoagulation treatment have also been shown to be at high risk of recurrence . Post thrombotic syndrome is a complication of a deep vein thrombosis which can lead to chronic venous insufficiency and ulceration . It has a cumulative incidence after 2 years of around 25 % and it has been suggested that extended oral anticoagulation should be investigated as a possible preventative measure . Methods / design Patients with a first idiopathic venous thromboembolism will be recruited through anticoagulation clinics and r and omly allocated to either continuing or discontinuing warfarin treatment for a further 2 years and followed up on a six monthly basis . At each visit D-dimer levels will be measured using a Roche Cobas h 232 POC device . In addition a venous sample will be taken for laboratory D-dimer analysis at the end of the study . Patients will be examined for signs and symptoms of PTS using the Villalta scale and complete VEINES and EQ5D quality of life question naires . Discussion The primary aim of the study is to investigate whether extending oral anticoagulation treatment ( prior to discontinuing treatment ) beyond 3–6 months for patients with a first unprovoked proximal deep vein thrombosis or pulmonary embolism prevents recurrence . The study will also determine the role of extending anticoagulation for patients with elevated D-dimer levels prior to discontinuing treatment and identify the potential of D-dimer point of care testing for identification of high risk patients within a primary care setting .Trial registration IS RCT Background — Dabigatran and warfarin have been compared for the treatment of acute venous thromboembolism ( VTE ) in a previous trial . We undertook this study to extend those findings . Methods and Results — In a r and omized , double-blind , double-dummy trial of 2589 patients with acute VTE treated with low-molecular-weight or unfractionated heparin for 5 to 11 days , we compared dabigatran 150 mg twice daily with warfarin . The primary outcome , recurrent symptomatic , objective ly confirmed VTE and related deaths during 6 months of treatment occurred in 30 of the 1279 dabigatran patients ( 2.3 % ) compared with 28 of the 1289 warfarin patients ( 2.2 % ; hazard ratio , 1.08 ; 95 % confidence interval [ CI ] , 0.64–1.80 ; absolute risk difference , 0.2 % ; 95 % CI , −1.0 to 1.3 ; P<0.001 for the prespecified noninferiority margin for both criteria ) . The safety end point , major bleeding , occurred in 15 patients receiving dabigatran ( 1.2 % ) and in 22 receiving warfarin ( 1.7 % ; hazard ratio , 0.69 ; 95 % CI , 0.36–1.32 ) . Any bleeding occurred in 200 dabigatran ( 15.6 % ) and 285 warfarin ( 22.1 % ; hazard ratio , 0.67 ; 95 % CI , 0.56–0.81 ) patients . Deaths , adverse events , and acute coronary syndromes were similar in both groups . Pooled analysis of this study RE-COVER II and the RE-COVER trial gave hazard ratios for recurrent VTE of 1.09 ( 95 % CI , 0.76–1.57 ) , for major bleeding of 0.73 ( 95 % CI , 0.48–1.11 ) , and for any bleeding of 0.70 ( 95 % CI , 0.61–0.79 ) . Conclusion — Dabigatran has similar effects on VTE recurrence and a lower risk of bleeding compared with warfarin for the treatment of acute VTE . Clinical Trial Registration — URL : www . clinical trials.gov . Unique identifiers : NCT00680186 and NCT00291330 Background — Recent studies have investigated alternatives to warfarin for stroke prophylaxis in patients with atrial fibrillation ( AF ) , but whether these alternatives are cost-effective is unknown . Methods and Results — On the basis of the results from R and omized Evaluation of Long Term Anticoagulation Therapy ( RE-LY ) and other trials , we developed a decision- analysis model to compare the cost and quality -adjusted survival of various antithrombotic therapies . We ran our Markov model in a hypothetical cohort of 70-year-old patients with AF using a cost-effectiveness threshold of $ 50 000/ quality -adjusted life-year . We estimated the cost of dabigatran as US $ 9 a day . For a patient with an average risk of major hemorrhage ( ≈3%/y ) , the most cost-effective therapy depended on stroke risk . For patients with the lowest stroke rate ( CHADS2 stroke score of 0 ) , only aspirin was cost-effective . For patients with a moderate stroke rate ( CHADS2 score of 1 or 2 ) , warfarin was cost-effective unless the risk of hemorrhage was high or quality of international normalized ratio control was poor ( time in the therapeutic range < 57.1 % ) . For patients with a high stroke risk ( CHADS2 stroke score ≥3 ) , dabigatran 150 mg ( twice daily ) was cost-effective unless international normalized ratio control was excellent ( time in the therapeutic range > 72.6 % ) . Neither dabigatran 110 mg nor dual therapy ( aspirin and clopidogrel ) was cost-effective . Conclusions — Dabigatran 150 mg ( twice daily ) was cost-effective in AF population s at high risk of hemorrhage or high risk of stroke unless international normalized ratio control with warfarin was excellent . Warfarin was cost-effective in moderate-risk AF population s unless international normalized ratio control was poor BACKGROUND Apixaban , an oral potent reversible direct inhibitor of activated factor X , has shown promise in the prevention of venous thromboembolism following major orthopedic surgery . We conducted a dose-ranging study in patients with deep vein thrombosis . METHODS Consecutive patients with symptomatic deep vein thrombosis were included and r and omized to receive 84 - 91 days of apixaban 5 mg twice-daily , 10 mg twice-daily , or 20 mg once-daily , or low molecular weight heparin ( LMWH ) followed by a vitamin K antagonist ( VKA ) . The primary efficacy outcome was the composite of symptomatic recurrent venous thromboembolism and asymptomatic deterioration of bilateral compression ultrasound or perfusion lung scan . The principal safety outcome was the composite of major and clinical ly relevant , non-major bleeding . RESULTS The mean age of the 520 included patients was 59 years , and 62 % were male . The primary outcome occurred in 17 of the 358 apixaban-treated patients [ 4.7 % , 95 % confidence interval ( CI ) 2.8 - 7.5 % ] and in five of the 118 LMWH/VKA-treated patients ( 4.2 % , 95 % CI 1.4 - 9.6 % ) who were evaluable . The incidence in all three apixaban groups was low and comparable without evidence of a dose response . The principal safety outcome occurred in 28 ( 7.3 % ) of the 385 apixaban-treated patients and in 10 ( 7.9 % ) of the 126 LMWH/VKA-treated patients . No dose response for apixaban was observed . CONCLUSION These observations warrant further evaluation of apixaban in phase III studies . The attractive fixed-dose regimen of this compound may meet the dem and to simplify anticoagulant treatment in patients with established venous thromboembolism Objectives To determine the incremental net health benefits of dabigatran etexilate 110 mg and 150 mg twice daily and warfarin in patients with non-valvular atrial fibrillation and to estimate the cost effectiveness of dabigatran in the United Kingdom . Design Quantitative benefit-harm and economic analyses using a discrete event simulation model to extrapolate the findings of the RE-LY ( R and omized Evaluation of Long-Term Anticoagulation Therapy ) study to a lifetime horizon . Setting UK National Health Service . Population Cohorts of 50 000 simulated patients at moderate to high risk of stroke with a mean baseline CHADS2 ( Congestive heart failure , Hypertension , Age≥75 years , Diabetes mellitus , previous Stroke/transient ischaemic attack ) score of 2.1 . Main outcome measures Quality adjusted life years ( QALYs ) gained and incremental cost per QALY of dabigatran compared with warfarin . Results Compared with warfarin , low dose and high dose dabigatran were associated with positive incremental net benefits of 0.094 ( 95 % central range −0.083 to 0.267 ) and 0.146 ( −0.029 to 0.322 ) QALYs . Positive incremental net benefits result ed for high dose dabigatran in 94 % of simulations versus warfarin and in 76 % of those versus low dose dabigatran . In the economic analysis , high dose dabigatran dominated the low dose , had an incremental cost effectiveness ratio of £ 23 082 ( € 26 700 ; $ 35 800 ) per QALY gained versus warfarin , and was more cost effective in patients with a baseline CHADS2 score of 3 or above . However , at centres that achieved good control of international normalised ratio , such as those in the UK , dabigatran 150 mg was not cost effective , at £ 42 386 per QALY gained . Conclusions This analysis supports regulatory decisions that dabigatran offers a positive benefit to harm ratio when compared with warfarin . However , no subgroup for which dabigatran 110 mg offered any clinical or economic advantage over 150 mg was identified . High dose dabigatran will be cost effective only for patients at increased risk of stroke or for whom international normalised ratio is likely to be less well controlled BACKGROUND Apixaban , an oral factor Xa inhibitor administered in fixed doses , may simplify the treatment of venous thromboembolism . METHODS In this r and omized , double-blind study , we compared apixaban ( at a dose of 10 mg twice daily for 7 days , followed by 5 mg twice daily for 6 months ) with conventional therapy ( subcutaneous enoxaparin , followed by warfarin ) in 5395 patients with acute venous thromboembolism . The primary efficacy outcome was recurrent symptomatic venous thromboembolism or death related to venous thromboembolism . The principal safety outcomes were major bleeding alone and major bleeding plus clinical ly relevant nonmajor bleeding . RESULTS The primary efficacy outcome occurred in 59 of 2609 patients ( 2.3 % ) in the apixaban group , as compared with 71 of 2635 ( 2.7 % ) in the conventional-therapy group ( relative risk , 0.84 ; 95 % confidence interval [ CI ] , 0.60 to 1.18 ; difference in risk [ apixaban minus conventional therapy ] Output:

RESULTS Apixaban ( Eliquis ® , Bristol-Myers Squibb , USA ; Pfizer , USA ) [ 5 mg bd ( twice daily ) ] was ranked as among the best interventions for stroke prevention in AF , and had the highest expected net benefit . Edoxaban ( Lixiana ® , Daiichi Sankyo , Japan ) [ 60 mg od ( once daily ) ] was ranked second for major bleeding and all-cause mortality . Neither the clinical effectiveness analysis nor the CEA provided strong evidence that NOACs should replace postoperative LMWH in primary prevention of VTE . For acute treatment and secondary prevention of VTE , we found little evidence that NOACs offer an efficacy advantage over warfarin , but the risk of bleeding complications was lower for some NOACs than for warfarin . For a willingness-to-pay threshold of > £ 5000 , apixaban ( 5 mg bd ) had the highest expected net benefit for acute treatment of VTE . Aspirin or no pharmacotherapy were likely to be the most cost-effective interventions for secondary prevention of VTE : our results suggest that it is not cost-effective to prescribe NOACs or warfarin for this indication . CONCLUSIONS NOACs have advantages over warfarin in patients with AF , but we found no strong evidence that they should replace warfarin or LMWH in primary prevention , treatment or secondary prevention of VTE .

MS214122

***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: W hat n ~ les of evidence should apply when evpert committees meet to generate recommendations for the clinical management of patients ? Should only the thoroughly vali date d results of r and omized clinical trials be admissible to avoid or minimize the application of useless or harmful therapy ? Or , to maximize the potential benefits to patients ( inclr ~ ding those possible from unproved remedies ) , should a synthesis of the experiences of experienced clinicians form the basis for such recommendations ? Ample precedent exists for the latter approach even when attempts are made to replace it . ' However , for the following reasons , the nonexperimental evidence that forms the recalled experiences of seasoned clinicians will tend to overestimate efficacy : A r and omized study was conducted on 66 patients with acute established oliguric renal failure . Intravenous doses of furosemide ranging from 1.5 to 6.0 mg/kg were given every 4 h to 33 of the patients ; the remaining 33 patients served as controls . A persisting diuretic response was observed in 5 treated patients and in 2 controls . Hemodialyses were required in most of them . Furosemide did not significantly modify in cured patients the mean oliguric period , the number of dialyses and the mean period of renal insufficiency Thirty-six patients with preoperative renal dysfunction were studied to evaluate the effects of dopamine ( D ) and dopamine-nitroprusside ( DN ) on renal function during cardiopulmonary bypass ( CPB ) . No differences from the control group ( C ) were found in creatinine clearance , fractional sodium excretion , osmolarity and free-water clearance . Sodium output/intake ratio during CPB was higher in group D than in groups C and DN ( P less than 0.05 ) ; water output/intake ratio was higher in group D than in group C ( P less than 0.05 ) . Urine lysozime levels and alpha-glycosidase/creatinine ratios increased similarly in the three groups , suggesting ischemic tubular cell damage . No patients showed acute postoperative renal failure or a worsening of their renal dysfunction . The data suggest an increased water and sodium excretion during CPB with a dopamine infusion , possibly result ing from a renal vasodilator effect that was abolished by simultaneous nitroprusside administration Fifty-eight patients in established acute renal failure following trauma or surgery were allocated in a prospect i ve and r and om fashion to two different diuretic regimes . In the control group , 1 g frusemide was given as a single injection over four hours . In the test group , frusemide was then continued either intravenously or orally in a dose of 3 g/24 hr until a urine output of 200 ml/hr was sustained or until the plasma creatinine fell below 300 mumoles/l . Oliguria was reversed or prevented in 24 of 28 patients given sustained frusemide , but in only 2 patients given a single injection . However , the number of dialyses and duration of renal failure and mortality were not different in the two groups . The serious complication of deafness occurred in two patients and in one of them this was permanent Previous studies suggest a role for renal vasoconstriction in the pathogenesis of radiocontrast-induced nephropathy ( RCIN ) . A renal vasodilator such as dopamine may be protective . However , the effect of dopamine on renal blood flow ( RBF ) in patients with chronic renal failure ( CRF ) is controversial . Patients with CRF of diabetic ( DM ) or nondiabetic ( NDM ) origin were hydrated with 0.45 % NaCl intravenously at 100 mL/h for 12 h and then r and omized to either 0.45 % NaCl IV at 100 mL/h ( Group 1 ) or dopamine IV at 2 micrograms/kg/min in 0.45 % NaCl at 100 mL/h for 2 h during and after cardiac catheterization . Mean arterial pressure ( MAP ) , cardiac output ( CO ) , and RBF were measured at baseline ( t = 0 ) , after 5 min of vehicle ( Group 1 ) or dopamine ( Group 2 ) but before ionic radiocontrast ( t = 5 min ) , after ventriculogram ( t = 15 min ) , and after coronary angiography ( t = 65 min ) . Serum creatinine ( SCr ) was measured at baseline and 24 and 48 h after cardiac catheterization . RCIN was defined as a 25 % increase of SCr above baseline 48 h after cardiac catheterization . Baseline characteristics demonstrated the groups to be equivalent in age , SCr , creatinine clearance , CO , MAP , RBF , and radiocontrast dose administered . The incidence of RCIN was not different between Group 1 and Group 2 ( Group 1 , 6 of 15 patients ; Group 2 , 5 of 15 patients ) . Dopamine infusion was associated with a significant increase in RBF at 5 min ( Group 1 , 110 + /- 13 % ; Group 2 , 193 + /- 40 % at t = 5 , p < .05 ) . RBF remained elevated throughout the catheterization in Group 2 . ( ABSTRACT TRUNCATED AT 250 WORDS PURPOSE To evaluate the protective effect of low-dose dopamine given as continuous infusion in patients who undergo chemotherapy with the nephrotoxin cisplatin . PATIENTS AND METHODS Forty-two patients who received high-dose cisplatin-containing chemotherapy entered a prospect i ve , r and omized , double-blind , placebo-controlled trial . Twenty-one patients received dopamine , and 21 received placebo . Patients were to receive either infusional dopamine 2 micrograms/kg/min over 48 hours or placebo . Cisplatin 125 mg/m2 was administered 12 hours after initiating dopamine ( group D ) or placebo ( group P ) . This schedule was repeated twice , 1 week apart . Measurements of serum creatinine , urinary electrolytes and creatinine , urinary excretion of epidermal growth factor ( EGF ) , ototoxicity , parameters of hematopoietic recovery , and duration of hospitalization were analyzed . RESULTS We observed an increase in serum creatinine level to a peak of 1.9 mg/dL ( range , 0.8 to 7.8 ) in the dopamine group , in comparison to 1.4 mg/dL ( range , 0.9 to 3.3 ) in the placebo group ( P = .04 ) . Urinary magnesium excretion increased and EGF excretion decreased in both groups . Urinary sodium , chloride , and potassium excretion were increased in both groups , but more so in the placebo group . Dopamine had no measurable effect on hearing loss , duration of hospitalization , or hematopoietic recovery . CONCLUSION The use of prophylactic dopamine increased peak serum creatinine levels relative to placebo and failed to prevent cisplatin-induced renal toxicity or ototoxicity . Determination of whether dopamine could reverse chemotherapy-induced renal damage would require a r and omized prospect i ve trial BACKGROUND Injections of radiocontrast agents are a frequent cause of acute decreases in renal function , occurring most often in patients with chronic renal insufficiency and diabetes mellitus . METHODS We prospect ively studied 78 patients with chronic renal insufficiency ( mean [ + /- SD ] serum creatinine concentration , 2.1 + /- 0.6 mg per deciliter [ 186 + /- 53 mumol per liter ] ) who underwent cardiac angiography . The patients were r and omly assigned to receive 0.45 percent saline alone for 12 hours before and 12 hours after angiography , saline plus mannitol , or saline plus furosemide . The mannitol and furosemide were given just before angiography . Serum creatinine was measured before and for 48 hours after angiography , and urine was collected for 24 hours after angiography . An acute radiocontrast-induced decrease in renal function was defined as an increase in the base-line serum creatinine concentration of at least 0.5 mg per deciliter ( 44 mumol per liter ) within 48 hours after the injection of radiocontrast agents . RESULTS Twenty of the 78 patients ( 26 percent ) had an increase in the serum creatinine concentration of at least 0.5 mg per deciliter after angiography . Among the 28 patients in the saline group , 3 ( 11 percent ) had such an increase in serum creatinine , as compared with 7 of 25 in the mannitol group ( 28 percent ) and 10 of 25 in the furosemide group ( 40 percent ) ( P = 0.05 ) . The mean increase in serum creatinine 48 hours after angiography was significantly greater in the furosemide group ( P = 0.01 ) than in the saline group . CONCLUSIONS In patients with chronic renal insufficiency who are undergoing cardiac angiography , hydration with 0.45 percent saline provides better protection against acute decreases in renal function induced by radiocontrast agents than does hydration with 0.45 percent saline plus mannitol or furosemide OBJECTIVE To determine the effect on renal function of postoperative continuous , intravenous furosemide after major thoraco-abdominal or vascular surgery . DESIGN R and omized , double-blind , placebo-controlled trial . SETTING Intensive care unit of a referral hospital in Eastern Switzerl and . METHODS Furosemide ( 1 mg/h ) or placebo was administered to 121 consecutive patients admitted to the intensive care unit after major abdominal , chest or vascular surgery and continued throughout the intensive care treatment period . Enrollment was performed during a 6 months period . No patient was excluded . Renal function was determined serially by measuring creatinine clearances and plasma creatinine concentrations . RESULTS Postoperatively , creatinine clearance decreased significantly to 83 % ( furosemide ) and to 81 % ( placebo group ) of the initial value ( p = 0.004 ) . This decrease was not affected significantly by furosemide . Retrospective subgroup analysis using stepwise regression also did not show any differences between the groups . Hypokalemia was detected in 36 ( furosemide ) versus 19 % of the blood sample ( placebo , p = 0.006 ) . CONCLUSIONS Low-dose intravenous furosemide appears to offer no advantage over placebo in an unselected group of patients with moderate postoperative renal impairment . As no patients with acute renal failure necessitating dialysis were observed during the study period , the effect of furosemide in more severe postoperative renal impairment and the effects of higher doses of loop diuretics remain to be investigated We have compared low dose dopamine with dobutamine in conserving renal function in 142 children younger than 10 yr undergoing cardiopulmonary bypass ( CPB ) . Patients were allocated r and omly to receive a continuous infusion of either dopamine 2.5 micrograms kg-1 min-1 ( group 1 ) or dobutamine 2.5 micrograms kg-1 min-1 ( group 2 ) from the time of induction of anaesthesia . Administration of inotropes and diuretics was controlled strictly to agreed regimens . There was no clinical or statistically significant difference between the two groups in postoperative urine output , serum concentration of creatinine , fractional sodium excretion or need for diuretic therapy . This was true also of the subgroup of patients who received no other inotropic support . However , the subgroup of patients in group 1 who underwent periods of CPB in excess of 2 h ( n = 17 ) had persistently greater postoperative serum concentrations of creatinine . Low dose dopamine did not appear to be superior to dobutamine for protection of renal function in these patients Objective : Low‐dose dopamine has been used in critically ill patients to minimize renal dysfunction without sufficient data to support its use . The aim of this study was to determine whether low‐dose dopamine improves renal function , and whether dobutamine , a nondopaminergic inotrope , improves renal function . Design : Prospect i ve , r and omized , double‐blind trial . Patients : Twenty‐three patients at risk for renal dysfunction were entered into the study . Five patients were later withdrawn . Study data for the remaining 18 patients were : mean age 55 yrs ; mean Acute Physiology and Chronic Health Evaluation ( APACHE ) II score of 18 ; mean weight 71 kg ) . The following conditions were present : mechanical ventilation ( n = 17 [ inverse‐ratio ventilation , n = 6 ] ) ; inotrope administration ( n = 11 ) ; sepsis ( n = 13 ) ; and adult respiratory distress syndrome or multiple organ failure syndrome ( n = 9 ) . Interventions : The study patients were administered dopamine ( 200 & mgr;g/min ) , dobutamine ( 175 & mgr;g/min ) , and placebo ( 5 % dextrose ) over 5 hrs each in a r and omized order . Ventilator setting s , fluid management , and preexisting inotropic support were not altered during the study . Measurements and Main Results : Systemic hemodynamic values and indices of renal function ( 4‐hr urine volume , fractional excretion of sodium , and creatinine clearance ) were measured during the last 4 hrs of each infusion . Dopamine Output:

Level I evidence exists against the use of diuretics for radiocontrast-induced acute tubular necrosis , and loop diuretics given after vascular surgery . There is level II evidence that diuretics do not improve outcome in patients with established acute renal failure . Level II evidence also exists against the use of dopamine in the prevention of acute tubular necrosis in multiple subsets of patients . Conclusions Routine use of diuretics or dopamine for the prevention of acute renal failure can not be justified on the basis of available evidence

MS214123

***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 Vitiligo is a common hypopigmentation disorder with significant psychological impact if occurring before adulthood . A pilot clinical trial to determine the feasibility of an RCT was conducted and is reported here . Methods 12 participants 12 to 35 years old were recruited to a prospect i ve open-label pilot trial and treated with 60 mg of st and ardized G. biloba two times per day for 12 weeks . The criteria for feasibility included successful recruitment , 75 % or greater retention , effectiveness and lack of serious adverse reactions . Effectiveness was assessed using the Vitiligo Area Scoring Index ( VASI ) and the Vitiligo European Task Force ( VETF ) , which are vali date d outcome measures evaluating the area and intensity of depigmentation of vitiligo lesions . Other outcomes included photographs and adverse reactions . Safety was assessed by serum coagulation factors ( platelets , PTT , INR ) at baseline and week 12 . Results After 2 months of recruitment , the eligible upper age limit was raised from 18 to 35 years of age in order to facilitate recruitment of the required sample size . Eleven participants completed the trial with 85 % or greater adherence to the protocol . The total VASI score improved by 0.5 ( P = 0.021 ) from 5.0 to 4.5 , range of scale 0 ( no depigmentation ) to 100 ( completely depigmented ) . The progression of vitiligo stopped in all participants ; the total VASI indicated an average repigmentation of vitiligo lesions of 15 % . VETF total vitiligo lesion area decreased 0.4 % ( P = 0.102 ) from 5.9 to 5.6 from baseline to week 12 . VETF staging score improved by 0.7 ( P = 0.101 ) from 6.6 to 5.8 , and the VETF spreading score improved by 3.9 ( P < 0.001 ) ) from 2.7 to -1.2 . There were no statistically significant changes in platelet count , PTT , or INR . Conclusions The criteria for feasibility were met after increasing the maximum age limit of the successful recruitment criterion ; participant retention , safety and effectiveness criteria were also met . Ingestion of 60 mg of Ginkgo biloba BID was associated with a significant improvement in total VASI vitiligo measures and VETF spread , and a trend towards improvement on VETF measures of vitiligo lesion area and staging . Larger , r and omized double-blind clinical studies are warranted and appear feasible . Trial Registration Clinical trials.gov registration number Objective : Pseudocatalase/superoxide dismutase ( PSD ) is a topical gel considered having therapeutic effects in vitiligo . This study was design ed to evaluate the efficacy of this combination in vitiligo . Methods : This was a pilot r and omized , double-blind , placebo-controlled trial on 46 symmetrical vitiligo lesions of limbs in 23 patients referring to dermatology clinics , Isfahan , Iran in 2010 . Patients were received this formula or placebo gels for the right and left lesions . Lesion area and degree of pigmentation were assessed at baseline , 2 , 4 , and 6 months . Findings : There were no significant changes in lesion area and perifollicular pigmentation in each group ( P > 0.05 ) . Conclusion : The results indicated no significant therapeutic effect for PSD in vitiligo Summary For effective treatment of vitiligo , it is as important to arrest the progression of the disease as it is to induce repigmentation . Recently , oxidative stress has been shown to play an important role in the pathogenesis of vitiligo . Ginkgo biloba extract has been shown to have antioxidant and immunomodulatory properties . In a double‐blind placebo‐controlled trial , we evaluated the efficacy of G. biloba extract in controlling the activity of the disease process in patients with limited and slow‐spreading vitiligo and in inducing repigmentation of vitiliginous areas . Fifty‐two patients were assigned to two treatment groups ( A and B ) in a double‐blind fashion , but only 47 patients could be evaluated , because one patient in group A and four patients in group B withdrew for reasons unrelated to the study . Patients in group A were given G. biloba extract 40 mg three times daily whereas patients in group B received placebo in similar doses . A statistically significant cessation of active progression of depigmentation was noted in patients treated with G. biloba ( P = 0.006 ) . Marked to complete repigmentation was seen in 10 patients in group A , whereas only two patients in group B showed similar repigmentation . The G. biloba extract was well tolerated . G. biloba extract seems to be a simple , safe and fairly effective therapy for arresting the progression of the disease Narrow-b and UVB has been reported to be efficacious in patients with vitiligo . The epidermis of patients with vitiligo showed reduction in the levels of catalase , in association with high levels of hydrogen peroxidase ( H2O2 ) that is toxic for melanocytes . Based on these findings , we studied the efficacy and safety of a topical gel containing catalase and superoxide dismutase ( Vitix ) in combination with narrow-b and UVB . The study included 22 patients of which 19 completed the 6-month study period . Patients applied the gel containing catalase and superoxide dismutase twice a day and received narrow-b and UVB 3 times per week . Two different dermatologists evaluated the grade of repigmentation by photograph comparison . At the end of therapy , more than 50 % of overall repigmentation was noticed in 11 of 19 ( 57.9 % ) patients . More than 75 % repigmentation was recorded in three ( 15.79 % ) , 26%-50 % repigmentation in six ( 31.58 % ) patients and 1%-25 % repigmentation in one ( 5.26 % ) patient , whereas one ( 5.26 % ) of 19 patients showed no repigmentation at all . The best response was achieved on the face and neck , with more than 50 % repigmentation observed in 11 of 14 ( 78.6 % ) patients . Development of new lesions was not observed . Adverse events were mild and transient . The study showed that the combination therapy of narrow-b and UVB and gel containing catalase and dismutase is a therapeutic option that could be considered in the management of vitiligo . Further evaluation of this combination in multicenter , double-blind , placebo-controlled studies should be undertaken Background : Generalized vitiligo is a disease with unpredictable bursts of activity , goal of treatment during the active phase being to stabilize the lesions . This emphasizes the need for a prospect i ve marker for monitoring disease activity to help decide the duration of therapy . Aims and Objectives : In the present study , we examined whether reactive oxygen species ( ROS ) generated in erythrocytes can be translated into a marker of activity in vitiligo . Material s and Methods : Level of intracellular ROS was measured flow cytometrically in erythrocytes from venous blood of 21 patients with generalized vitiligo and 21 healthy volunteers using the probe dichlorodihydrofluorescein diacetate . Results : The levels of ROS differed significantly between patients and healthy controls , as well as between active versus stable disease groups . In the active disease group , ROS levels were significantly lower in those being treated with systemic steroids than those that were not . ROS levels poorly correlated with disease duration or body surface area involved . Conclusion : A long-term study based on these findings can be conducted to further vali date the potential role of ROS in monitoring disease activity vitiligo Narrow b and UVB is succeeding psoralen and UVA irradiation as the main treatment of vitiligo vulgaris in several European countries . Vitamin B12 and folic acid deficiency in some vitiligo patients has prompted research ers to investigate the efficacy of these vitamins in the treatment of vitiligo . In the present controlled study we investigated the value of narrow b and UVB phototherapy in the treatment of vitiligo and the possible additive effect of vitamin B12 and folic acid . Twenty-seven patients with long-term stable vitiligo were included and r and omized in a " UVB only " ( UVB ) or " UVB combined with vitamin B12 and folic acid " ( UVB+ ) group . Patients were irradiated thrice weekly for one year , whilst repigmentation was carefully monitored . In 92 % ( 25/27 ) of the patients up to 100 % repigmentation was seen . Repigmentation was notable in lesions on the face , neck and throat , lower arm , chest , back and lower legs , whilst repigmentation on the h and s , wrists , feet and ankles proved to be minimal . Maximum repigmentation rates did not differ significantly between the UVB group and the UVB+ group . Our study reconfirms that narrow b and UVB phototherapy is an effective treatment for vitiligo and shows that co-treatment with vitamin B12 and folic acid does not improve the outcome of treatment of vitiligo with narrow b and UVB phototherapy Phyllanthus emblica , vitamin E , and caroteinods are compounds showing antioxidative , anti-inflammatory , and repigmenting effects , whose role in vitiligo treatment has not been evaluated so far . Sixty-five subjects ( group A ) were treated with one tablet of an oral supplement containing P. emblica ( 100 mg ) , vitamin E ( 10 mg ) , and carotenoids ( 4.7 mg ) three times/day for 6 months and compared with a control group ( group B , 65 patients ) , which instead was not treated with antioxidants . Both groups were simultaneously treated with a comparable topical therapy and /or phototherapy . After a 6 months follow-up , a significantly higher number of patients in group A had a mild repigmentation on the head/neck regions ( p = 0.019 ) and on the trunk ( trend , p = 0.051 ) . The number of patients who presented no repigmentation in head/neck , trunk , upper , and lower limbs was significantly higher in group B ( respectively , p = 0.009 , p = 0.001 , p = 0.001 , p = 0.025 ) . Moreover , group B patients showed higher signs of inflammation ( p = 0.002 ) , a more rapid growth of the lesions ( p = 0.039 ) , a higher percentage of worsening disease ( p = 0.003 ) , and more erythema ( p = 0.059 ) , whereas group A patients showed a higher percentage of steady disease ( p = 0.065 ) . Our results suggest that the supplement with antioxidants in patients with vitiligo might represent a valuable instrument to increase the effectiveness of other vitiligo treatments . [ Correction added after online publication 06-Oct-2014 : the dosages of vitamin E and carotenoids have been up date d. ] Background : Vitiligo is an acquired idiopathic cutaneous disease characterized by pearly white patches of variable shapes and sizes . Various medical and surgical therapeutic options have been proposed to achieve repigmentation ; phototherapy is one of the most efficient options . Topical therapies have been a mainstay of vitiligo treatment , with or without phototherapy . Aim of the work : To compare the efficacy of combined topical antioxidant hydrogel and excimer light versus excimer light alone in treating vitiligo . Patients and Methods : Thirty patients were included in this comparative , prospect i ve , r and omized study . For each patient , at least 2–4 vitiliginous macules were r and omly selected and treated while an untreated vitiliginous macule served as control . Lesions were divided into two groups : Group A received combination therapy of daily topical antioxidant plus excimer light , while Group B received only excimer light . Lesions were treated twice a week for a maximum of 24 sessions . Initial fluencies were adjusted individually according to the minimal erythema dose in vitiliginous skin . Efficacy based on repigmentation percentages were blindly evaluated by two independent physicians . Results : Group A lesions showed significant efficacy than group B ( p < 0.001 ) , specially on treating UV-sensitive lesions with no side effects . Conclusion : Topical antioxidant and excimer light represents a valuable , effective therapy for localized vitiligo BACKGROUND Among all the topical immunomodulators , vitiligo 's mainstay therapy includes topical corticosteroids . Many other non-immune theories have also been suggested for vitiligo 's pathogenesis , but the role of oxidative stress has gained more importance in recent years . OBJECTIVE To compare the effect of topical 0.05 % betamethasone vs. catalase/dismutase superoxide ( C/DSO ) . STUDY DESIGN R and omized , matched-paired , double-blind trial . SETTING Dermatology Section , University of Antioquia , Medellín , Colombia . SUBJECTS Patients ( aged > 18 years or between 12 and 18 years ) with parent 's informed consent , with stable or active bilateral vitiligo . INTERVENTION Topical 0.05 % betamethasone or C/DSO . METHODS Two lesions similar to each other in size were chosen . All assessment s were made by two blinded investigators , and photographs were subjected to morphometry analysis . MAIN OUTCOME Skin repigmentation by digital morphometry . RESULTS Twenty-five patients were enrolled in the study ( 21 women and 4 men ) . Mean age of participants was 40 years ( range : 12 - 74 years ) . One patient on C/DSO experienced a mild local erythematous papular rash that self-resolved . Output:

RESULTS A deregulated oxidative pathway is clearly evident with elevated superoxide dismutase , decreased catalase and increased lipid peroxidation . However , similar results have been obtained in other inflammatory skin diseases such as psoriasis , atopic dermatitis , lichen planus and urticaria . Some isolated successes have been reported with oral ginkgo biloba , polypodium leucotomos and vitamin C and E preparations , while other clinical trials have failed to show reproducible results . The use of topical antioxidants delivers in general no beneficial results . The oxidative pathway is affected in vitiligo , but its unique initiating or contributory role in the pathogenesis is less evident .

MS214124

***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: Eighty-seven male inmates from a state prison and 70 inmates from a county jail volunteered as subjects . The subjects , age 20 to 35 yrs , were assigned r and omly into a control or exercise group . Their Vo2max and treadmill performance values were determined before and after a 20 week jogging program . Training intensity was between 85 and 90 percent of maximum heart rate and involved workouts 3 days/week for 15 , 30 , or 45-min duration at the state prison and for 30-min 1 , 3 , or 5 days/week at the country jail . Cardiorespiratory fitness improved in direct proportion to frequency and duration of training . Injury , occurred in 22 % , 24 % and 54 % of the 15 , 30 , and 45-min duration groups and in 0 % , 12 % , and 39 % of the 1 , 3 , and 5-day/week groups , respectively . Attrition result ing from injury occurred in 0 % , 0 % , and 17 % and in 0 % , 4 % , and 6 % of the same respective groups . Attrition due to lack of interest was similar for all training groups ( 25 % ) , but was significantly lower in the control groups ( 10 % ) . Although the results showed a greater increase in cardiorespiratory fitness for the 45-min duration and 5-day/week groups , these programs are not recommened for beginning joggers because of the significantly greater percent of injuries In a r and omized prospect i ve study among 390 recruits , the hypothesis that improved shoe shock attenuation could lessen the incidence of overuse injuries was tested . During the 14 weeks of training , 90 % of the recruits sustained overuse injuries . Recruits training in a modified basketball shoe had a statistically significant lower incidence of metatarsal stress fractures and foot overuse injuries , compared with st and ard infantry boots , but their overall incidence of overuse injuries was not reduced . The effect of improved shoe shock attenuation was limited to those overuse injuries result ing from vertical impact loads Three hundred fifty male recruits were r and omly allocated to either the st and ard recruit training program ( N = 180 ) or substituted a weighted-march activity for all formal run periods ( N = 170 ) in the physical training program . All injuries were seen at a single medical facility , and the cause , location , and severity of injury were recorded in the medical documents . Lower-limb injuries constituted 79.8 % of all Run injuries and 61.1 % of all Walk injuries . Foot ( 18.9 % ) , knee ( 16.7 % ) , ankle ( 13.3 % ) , and shoulder ( 8.9 % ) were the most common sites of injury in the Walk group . In the Run group , the most common sites were knee ( 32.1 % ) , ankle ( 18.3 % ) , foot ( 11.9 % ) , and shin ( 7.3 % ) . There were two stress fractures ( tibial ) in the Run group and none in the Walk group , giving the Run group an incidence of 1.1 % . There were 10 medical discharges in the Walk group and 16 in the Run group . Ten ( 62.5 % ) of the Run and 2 ( 20 % ) of the Walk discharges were due to lower-limb causes . Of these , only 1 ( 10 % ) of the Walk and 4 ( 25 % ) of the Run injuries were not considered to be pre-existing conditions . Marching ( 30.0 % ) , physical training ( 25.5 % ) , and the obstacle course ( 11.1 % ) were the most frequent causes of injury in the Walk group . In the Run group , the leading causes were running ( 36.6 % ) , physical training ( 19.2 % ) , and the obstacle course ( 14.6 % ) . Running was the major cause of knee injury in the Run group ( 17/35 ) , whereas physical training was the major cause of knee injury in the Walk group ( 5/15 ) . Running was also the major cause of other lower-limb injuries in the Run group ( 19/58 ) , whereas marching was the major cause in the Walk group ( 19/50 ) . Lower-limb injuries were more frequent in the Run group , with running cited as the major cause of these injuries Soccer referees participating in large soccer tournaments may develop overuse injuries . In this study the effect of shock absorbing heel inserts in the incidence of soreness was investigated . Forty-eight referees were r and omly selected to wear shock absorbing heel inserts ( SAH ) in the 5 day-tournament , while 43 referees were the control group . A daily question naire inquiring about complaints from the locomotive system was completed for each referee and in case of any soreness they were examined by doctors to document and classify the anatomical site . Calf , thigh , back , achilles tendon and knee were the most common localizations of overuse symptoms . The incidence of soreness in achilles tendon , calf and back were significantly reduced by the use of ( SAH ) inserts Three hundred fifty male recruits were r and omly allocated to either the st and ard recruit training program ( N = 180 ) or substituted a weighted march activity for all running periods in the physical training program ( N = 170 ) . There were no other differences in the formal training program . The incidence of injury was 37.6 and 46.6 % in the walk and run groups , respectively . The rate of injury was 52.9/100 recruits in the walk group and 61.7/100 in the run group . The exposure incidence was 12.8/1,000 hours of physical training in the walk group and 14.9/1,000 hours in the run group . There was no statistically significantly difference in the total number of injured recruits in the two groups ( 64 vs. 85 , chi(2 ) = 2.90 , p = 0.09 , relative risk [ RR ] = 1.24 ) . There were , however , significantly more lower-limb ( 43 vs. 75 , chi(2 ) = 9.77 , p = 0.0018 , RR = 1.65 ) and knee injuries ( 15 vs. 35 , chi(2 ) = 6.54 , p = 0.011 , RR = 2.14 ) in the Run group . Lower-limb injuries constituted 79.8 % of all Run injuries and 61.1 % of all Walk injuries . Injuries in the Run group produced more morbidity , with nearly double the number of days of restriction , hospitalization , and not fit for duty . St and ardized morbidity rates showed an average of 5.4 days of restriction per injury in the Run group and 3.96 days of restriction per injury in the Walk group . Reduction of running distance in the physical training program result ed in significant reductions in both the incidence of lower-limb injury and the overall severity of injury The purpose of this intervention study was to prove that increasing flexibility of the hamstring musculotendinous unit would decrease the number of lower extremity overuse injuries that occur in military infantry basic trainees . Two different companies going through basic training at the same time were used . Hamstring flexibility was checked at the beginning and at the end of the 13-week infantry basic training course . The control company ( N 148 ) proceeded through normal basic training . The intervention company ( N 150 ) followed the same program but added three hamstring stretching sessions to their already scheduled fitness program . All subsequent lower extremity overuse injuries were recorded through the troop medical clinic . Hamstring flexibility increased significantly in the intervention group compared with the control group . The number of injuries was also significantly lower in the intervention group . Forty-three injuries occurred in the control group for an incidence rate of 29.1 % , compared with 25 injuries in the intervention group for an incidence rate of 16.7 % . Thus , in this study , the number of lower extremity overuse injuries was significantly lower in infantry basic trainees with increased hamstring flexibility Our prospect i ve study evaluates the use of a knee brace with a silicon patellar support ring as a method of preventing anterior knee pain from developing in young persons undergoing strenuous physical exercise . We studied 60 young athletes , who qualified for a strenu ous physical training course and who had not suffered from anterior knee pain previously . Twenty-seven sub jects were in the brace group and 33 were in the nonbrace control group . The incidence of anterior knee pain syndrome increased with the intensity of exertion as the study progressed ; i.e. , subjects ran 6 km in the 1 st week , gradually increasing each week up to 42 km/week at the 8th week . Yet , there was a significant reduction in the incidence of the syndrome at the end of the study in male athletes who had applied the braces before exercise sessions and in the brace group as a whole , compared with the control group . Prophylactic use of the brace , as described , did not reduce the ability of the athletes who wore braces to improve their physical fitness parameters in response to exercise . These data indicate that the use of a brace may be an effective way to prevent the development of anterior knee pain syndromes in persons participating in strenuous and intensive physical exercise Sedentary individuals , particularly new military recruits , who start a physical training program have a substantial risk of developing an overuse injury of the lower limb . In this study we investigated the effect of neoprene insoles on the incidence of overuse injuries during 9 weeks of basic military training . The experimental group consisted of 237 r and omly selected new recruits , while 1151 recruits were the control group . Insoles were given to the experimental group and compliance was monitored . A panel of doctors documented and classi fied all injuries occurring during the 9 week period . A total of 54 ( 22.8 % ) and 237 ( 31.9 % ) injuries were reported in the experimental and control groups , re spectively . In both groups , the majority of injuries were overuse ( experimental group , 90.7 % ; control group , 86.4 % ) . The mean weekly incidence of total overuse injuries and tibial stress syndrome was significantly lower ( P < 0.05 ) in the experimental group . The mean incidence of stress fractures was lower in the experimental group but not significantly so ( 0.05 < P < 0.1 ) . This study shows that the incidence of total overuse injuries and tibial stress syndrome during 9 weeks of basic military training can be reduced by wearing insoles The purpose of this study was to evaluate the effect of a health education intervention on running injuries . The intervention consisted of information on , and the sub sequent performance of , st and ardized warm-up , cool- down , and stretching exercises . Four hundred twenty- one male recreational runners were matched for age , weekly running distance , and general knowledge of preventing sports injuries . They were r and omly split into an intervention and a control group : 167 control and 159 intervention subjects participated throughout the study . During the 16-week study , both groups kept a daily diary on their running distance and time , and reported all injuries . In addition , the intervention group was asked to note compliance with the st and ardized program . At the end of the study period , knowledge and attitude were again measured . There were 23 injuries in the control group and 26 in the intervention group . Injury incidence for control and intervention sub jects was 4.9 and 5.5 running injuries per 1000 hours , respectively . The intervention was not effective in re ducing the number of running injuries ; it proved signifi cantly effective ( P < 0.05 ) in improving specific knowl edge of warm-up and cool-down techniques in the intervention group . This positive change can perhaps be regarded as a first step on the way to a change of behavior , which may eventually lead to a reduction of running injuries PURPOSE This study investigated the effect of muscle stretching during warm-up on the risk of exercise-related injury . METHODS 1538 male army recruits were r and omly allocated to stretch or control groups . During the ensuing 12 wk of training , both groups performed active warm-up exercises before physical training sessions . In addition , the stretch group performed one 20-s static stretch under supervision for each of six major leg muscle groups during every warm-up . The control group did not stretch . RESULTS 333 lower-limb injuries were recorded during the training period , including 214 soft-tissue injuries . There were 158 injuries in the stretch group and 175 in the control group . There was no significant effect of preexercise stretching on all-injuries risk ( hazard ratio [ HR ] = 0.95 , 95 % CI 0.77 - 1.18 ) , soft-tissue injury risk ( HR = 0.83 , 95 % CI 0.63 - 1.09 ) , or bone injury risk ( HR = 1.22 , 95 % CI 0.86 - 1.76 ) . Fitness ( 20-m progressive shuttle run test score ) , age , and enlistment date all significantly predicted injury risk ( P < 0.01 for each ) , but height , weight , and body mass index did not . CONCLUSION A typical muscle stretching protocol performed during preexercise warm-ups does not produce clinical ly meaningful reductions in risk of exercise-related injury in army recruits . Fitness may be an important , modifiable risk factor Output:

RESULTS Exposure to a high training load ( duration , frequency , or running distance ) increases the risk of injury , and thus modification of the training schedule can reduce the incidence of injury . Wearing a knee brace with a patellar support ring may be effective in the prevention of anterior knee pain caused by running . This review provides evidence for the effectiveness of the modification of training schedules in reducing lower limb soft tissue running injuries .

MS214125

***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 acute metabolic and cardiovascular responses to walking exercise at an intensity corresponding to the heart rate of claudication pain onset and to investigate the effects of a 12-week walking training program at this intensity on walking capacity . METHODS : Twenty-nine patients with intermittent claudication were r and omly allocated to the walking training ( n = 17 ) or control ( CO , n = 12 ) group . The walking training group performed an acute exercise session comprising 15 × 2-min bouts of walking at the heart rate of claudication pain onset , with 2-min interpolated rest intervals . The claudication symptoms and cardiovascular and metabolic responses were evaluated . Walking training was then performed at the same intensity twice each week for 12 weeks , while the control group engaged in twice weekly stretching classes . The claudication onset distance and total walking distance were evaluated before and after the interventions . Brazilian Registry Clinical Trials : RBR-7M3D8W . RESULTS : During the acute exercise session , the heart rate was maintained within tight limits . The exercise intensity was above the anaerobic threshold and > 80 % of the heart rate peak and VO2peak . After the exercise training period , the walking exercise group ( n = 13 ) showed increased claudication onset distance ( 309±153 vs. 413±201 m ) and total walking distance ( 784±182 vs. 1,100±236 m ) compared to the control group ( n = 12 ) ( p<0.05 ) . CONCLUSION : Walking exercise prescribed at the heart rate of claudication pain onset enables patients with intermittent claudication to exercise with tolerable levels of pain and improves walking performance BACKGROUND This prospect i ve , r and omized controlled clinical trial determined whether an optimal exercise program length exists to efficaciously change claudication onset time ( COT ) and peak walking time ( PWT ) in patients with peripheral artery disease and claudication . METHODS The study r and omized 142 patients to supervised exercise ( n = 106 ) or a usual care control group ( n = 36 ) , with 80 completing the exercise program and 27 completing the control intervention . The exercise program consisted of intermittent walking to nearly maximal claudication pain 3 days per week . COT and PWT were the primary outcomes obtained from a treadmill exercise test at baseline and bimonthly during the study . RESULTS After exercise , changes in COT ( P < .001 ) and PWT ( P < .001 ) were consistently greater than changes after the control intervention . In the exercise program , COT and PWT increased from baseline to month 2 ( P < .05 ) and from months 2 to 4 ( P < .05 ) but did not significantly change from months 4 to 6 ( P > .05 ) . When changes were expressed per mile walked during the first 2 months , middle 2 months , and final 2 months of exercise , COT and PWT only increased during the first 2 months ( P < .05 ) . CONCLUSIONS Exercise-mediated gains in COT and PWT occur rapidly within the first 2 months of exercise rehabilitation and are maintained with further training . The clinical significance is that a relatively short 2-month exercise program may be preferred to a longer program to treat claudication because adherence is higher , costs associated with personnel and use of facilities are lower per patient , and more patients can be trained for a given amount of personnel time and re source utilization BACKGROUND In patients with intermittent claudication , a supervised walking exercise program increases peak exercise performance and community-based functional status . Patients with peripheral arterial disease also have muscle weakness in the affected extremity that may contribute to the walking impairment . However , the potential benefits of training modalities other than walking exercise , such as strength training , have not been critically evaluated in this patient population . The present study tested the hypothesis that a strength training program would be as effective as treadmill walking exercise and that combinations of strengthening and walking exercise would be more effective than either alone in improving exercise performance . METHODS AND RESULTS Twenty-nine patients with disabling claudication were r and omized to 12 weeks of supervised walking exercise on a treadmill ( 3 h/wk at a work intensity sufficient to produce claudication ) , strength training ( 3 h/wk of resistive training of five muscle groups of each leg ) , or a nonexercising control group . Grade d treadmill testing was performed to maximally tolerated claudication pain to define changes in peak exercise performance . After 12 weeks , patients in the treadmill training program had a 74 + /- 58 % increase in peak walking time as well as improvements in peak oxygen consumption ( VO2 ) and the onset of claudication pain . Patients in the strength-trained group had a 36 + /- 48 % increase in peak walking time but no change in peak VO2 or claudication onset time . Control subjects had no changes in any of these measures over the 12-week period . After the first 12 weeks , patients in the initial walking exercise group continued for 12 more weeks of supervised treadmill training . This result ed in an additional 49 + /- 53 % increase in peak walking time ( total of 128 + /- 99 % increase over the 24 weeks ) . After the initial 12 weeks , patients in the strength-trained group began 12 weeks of supervised treadmill training , and patients in the control group participated in a 12-week combined program of strengthening and treadmill walking exercise . The combined strength and treadmill training program and treadmill training after 12 weeks of strength training result ed in increases in peak exercise performance similar to those observed with 12 weeks of treadmill training alone . CONCLUSIONS A supervised treadmill walking exercise program is an effective means to improve exercise performance in patients with intermittent claudication , with continued improvement over 24 weeks of training . In contrast , 12 weeks of strength training was less effective than 12 weeks of supervised treadmill walking exercise . Finally , strength training , whether sequential or concomitant , did not augment the response to a walking exercise program PURPOSE A pilot study was conducted to test the feasibility of supervised treadmill exercise training to improve functioning in study participants with peripheral arterial disease who did not have classical symptoms of intermittent claudication . METHODS For this study , 32 men and women with peripheral arterial disease but no symptoms of claudication were r and omized to exercise training or usual care . The intervention was a 12-week supervised treadmill walking program . Outcomes included 6-minute walk distance , maximum treadmill walking distance , and 4-meter walking velocity . Participant-reported community walking ability was measured with the Walking Impairment Question naire ( WIQ ) . Inflammatory blood factor levels also were measured . RESULTS Altogether , 25 participants who completed follow-up testing were included in intention-to-treat analyses . Of 24 participants ( 58 % ) r and omized to exercise , 14 completed the entire exercise training program . The participants r and omized to the intervention showed greater improvement in their WIQ walking speed score than the control subjects ( P = .05 ) . The participants r and omized to the intervention showed improvements in their 6-minute walk distance ( 1134 + /- 347 vs 1266 + /- 295 feet ; P = .03 ) , maximal treadmill walking distance ( 389 + /- 248 vs 585 + /- 293 feet ; P < .001 ) , WIQ distance score ( 52.3 + /- 29.1 vs 63.1 + /- 25.1 ; P = .002 ) , and WIQ speed score ( 48.7 + /- 26.8 vs 59.7 + /- 22.7 ; P = .008 ) . The participants r and omized to the control condition showed improvements in maximal treadmill walking distance ( 362 + /- 180 vs 513 + /- 237 feet ; P = .014 ) . There were no significant changes in the inflammatory blood factors after exercise . CONCLUSIONS This pilot study demonstrated that a supervised treadmill walking program may be feasible and may improve functioning for individuals with peripheral arterial disease who do not have classical symptoms of intermittent claudication . Further study is needed with a larger sample to identify optimal exercise methods that improve lower extremity functioning in men and women with peripheral arterial disease who do not have intermittent claudication Patients with atherosclerotic peripheral arterial disease ( PAD ) of the lower extremities have impaired walking ability due to exercise-induced muscle ischemia and the result ant pain of intermittent claudication . To evaluate the benefit of exercise training as a treatment for patients with PAD , as well as possible mechanisms associated with improvement , we r and omly assigned 19 men with disabling claudication to treated and control groups . Treatment consisted of supervised treadmill walking ( 1 hr/day , 3 days/wk , for 12 weeks ) with progressive increases in speed and grade as tolerated . Grade d treadmill testing was performed to maximal toleration of claudication pain on entry and after 12 weeks of training to define changes in peak exercise performance . After 12 weeks , treated subjects had increased their peak walking time 123 % , peak oxygen consumption 30 % , and pain-free walking time 165 % ( all p less than 0.05 ) . Control subjects had no change in peak oxygen consumption , but after 12 weeks , peak walking time increased 20 % ( p less than 0.05 ) . In treated subjects , maximal calf blood flow ( measured by a plethysmograph ) increased 38 + /- 45 % ( p less than 0.05 ) , but the change in flow was not correlated to the increase in peak walking time . Elevated plasma concentrations of acylcarnitines have been associated with the functional impairment of PAD and may reflect the metabolic state of ischemic skeletal muscle . In treated subjects , a 26 % decrease in resting plasma short-chain acylcarnitine concentration was correlated with improvement in peak walking time ( r = -0.78 , p less than 0.05 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Background — This prospect i ve , r and omized , controlled clinical trial compared changes in exercise performance and daily ambulatory activity in peripheral artery disease patients with intermittent claudication after a home-based exercise program , a supervised exercise program , and usual-care control . Methods and Results — Of the 119 patients r and omized , 29 completed home-based exercise , 33 completed supervised exercise , and 30 completed usual-care control . Both exercise programs consisted of intermittent walking to nearly maximal claudication pain for 12 weeks . Patients wore a step activity monitor during each exercise session . Primary outcome measures included claudication onset time and peak walking time obtained from a treadmill exercise test ; secondary outcome measures included daily ambulatory cadences measured during a 7-day monitoring period . Adherence to home-based and supervised exercise was similar ( P=0.712 ) and exceeded 80 % . Both exercise programs increased claudication onset time ( P<0.001 ) and peak walking time ( P<0.01 ) , whereas only home-based exercise increased daily average cadence ( P<0.01 ) . No changes were seen in the control group ( P>0.05 ) . The changes in claudication onset time and peak walking time were similar between the 2 exercise groups ( P>0.05 ) , whereas the change in daily average cadence was greater with home-based exercise ( P<0.05 ) . Conclusions — A home-based exercise program , quantified with a step activity monitor , has high adherence and is efficacious in improving claudication measures similar to a st and ard supervised exercise program . Furthermore , home-based exercise appears more efficacious in increasing daily ambulatory activity in the community setting than supervised exercise . Clinical Trial Registration — URL : http://www . Clinical Trials . Gov . Unique identifier : NCT00618670 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 molecular mechanisms by which physical training improves peripheral and coronary artery disease are poorly understood . Bone marrow-derived endothelial progenitor cells ( EPCs ) are thought to exert beneficial effects on atherosclerosis , angiogenesis , and vascular repair . METHODS AND RESULTS To study the effect of physical activity on the bone marrow , EPCs were quantified by fluorescence-activated cell sorter analysis in mice r and omized to running wheels ( 5.1+/-0.8 km/d , n=12 to 16 per group ) or no running wheel . Numbers of EPCs circulating in the peripheral blood of trained mice were enhanced to 267+/-19 % , 289+/-22 % , and 280+/-25 % of control levels after 7 , 14 , and 28 days , respectively , accompanied by a similar increase of EPCs in the bone marrow and EPCs exp and ed from spleen-derived mononuclear cells . eNOS-/- mice and wild-type mice treated with N(G)-nitro-l-arginine methyl ester showed lower EPC numbers at baseline and a significantly attenuated increase of EPC in response to physical activity . Exercise NO dependently increased serum levels of vascular endothelial growth factor and reduced the rate of apoptosis in spleen-derived EPCs . Running inhibited neointima formation after carotid artery injury by 22+/-2 % . Output:

Subgroup analyses indicated that a lesser improvement in MWD was observed in the subgroup with more diabetes patients , and that the subgroup with better baseline walking ability exhibited greater improvement in walking performance . In addition , similar improvements in walking performance were observed for exercise programs of different duration s and modalities . Regardless of exercise length and modality , regularly intensive walking exercise improves walking ability in PAD patients more than usual care . The presence of diabetes may attenuate the improvements in walking performance in patients with PAD following exercise

MS214126

***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 Our objectives are to describe the outcomes of patients presenting to the emergency department ( ED ) because of an adverse drug event and to compare them with outcomes of patients presenting for other reasons . METHODS This prospect i ve observational study was conducted at Vancouver General Hospital , a 955-bed tertiary care hospital . We prospect ively enrolled adults presenting to the ED between March and June 2006 , using a systematic sampling algorithm . Pharmacists and physicians independently evaluated patients for adverse drug events . An independent committee review ed and adjudicated cases in which assessment s were discordant or uncertain . Data from the index visit were linked to vital statistics , administrative health services utilization , and cost of care data . RESULTS Of 1,000 patients , 122 ( 12.2 % ; 95 % confidence interval [ CI ] 10.3 % to 14.4 % ) presented to the ED because of an adverse drug event . Of these , 48 presented because of an adverse drug reaction ( one type of adverse drug event defined as an unintended response that occurred despite use of an appropriate drug dosage ) . We found no difference in mortality among patients presenting with and without adverse drug reactions ( 14.6 % versus 5.9 % ; hazard ratio 1.57 ; 95 % CI 0.70 to 3.52 ) . After adjustment , patients with adverse drug events had a higher risk of spending additional days in the hospital per month ( 6.3 % versus 3.4 % ; odds ratio 1.52 ; 95 % CI 1.43 to 1.62 ) and higher rate of outpatient health care encounters ( 1.73 versus 1.22 ; rate ratio 1.20 ; 95 % CI 1.03 to 1.40 ) . The adjusted median monthly cost of care was 1.90 times higher ( Can $ 325 versus $ 96 ; 95 % CI 1.18 to 3.08 ) . CONCLUSION ED patients presenting with an adverse drug event incurred greater health services utilization and costs during a 6-month follow-up period compared with patients presenting for other reasons PURPOSE Results of the 2011 ASHP national survey of pharmacy practice in hospital setting s that pertain to dispensing and administration are presented . METHODS A stratified r and om sample of pharmacy directors at 1401 general and children 's medical-surgical hospitals in the United States were surveyed by mail . RESULTS In this national probability sample survey , the response rate was 40.1 % . De central ization of the medication-use system continues , with 40 % of hospitals using a de central ized system and 58 % of hospitals planning to use a de central ized model in the future . Automated dispensing cabinets were used by 89 % of hospitals , robots were used by 11 % , carousels were used in 18 % , and machine-readable coding was used in 34 % of hospitals to verify doses before dispensing . Overall , 65 % of hospitals had a United States Pharmacopeia chapter 797 compliant cleanroom for compounding sterile preparations . Medication administration records ( MARs ) have become increasingly computerized , with 67 % of hospitals using electronic MARs . Bar-code-assisted medication administration was used in 50 % of hospitals , and 68 % of hospitals had smart infusion pumps . Health information is becoming more electronic , with 67 % of hospitals having partially or completely implemented an electronic health record and 34 % of hospitals having computerized prescriber order entry . The use of these technologies has substantially increased over the past year . The average number of full-time equivalent staff per 100 occupied beds averaged 17.5 for pharmacists and 15.0 for technicians . Directors of pharmacy reported declining vacancy rates for pharmacists . CONCLUSION Pharmacists continue to improve medication use at the dispensing and administration steps of the medication-use system . The adoption of new technology is changing the philosophy of medication distribution , and health information is rapidly becoming electronic Objectives : We aim ed to assess the impact of an automated dispensing system on the incidence of medication errors related to picking , preparation , and administration of drugs in a medical intensive care unit . We also evaluated the clinical significance of such errors and user satisfaction . Design : Preintervention and postintervention study involving a control and an intervention medical intensive care unit . Setting : Two medical intensive care units in the same department of a 2,000-bed university hospital . Patients : Adult medical intensive care patients . Interventions : After a 2-month observation period , we implemented an automated dispensing system in one of the units ( study unit ) chosen r and omly , with the other unit being the control . Measurements and Main Results : The overall error rate was expressed as a percentage of total opportunities for error . The severity of errors was classified according to National Coordinating Council for Medication Error Reporting and Prevention categories by an expert committee . User satisfaction was assessed through self-administered question naires completed by nurses . A total of 1,476 medications for 115 patients were observed . After automated dispensing system implementation , we observed a reduced percentage of total opportunities for error in the study compared to the control unit ( 13.5 % and 18.6 % , respectively ; p < .05 ) ; however , no significant difference was observed before automated dispensing system implementation ( 20.4 % and 19.3 % , respectively ; not significant ) . Before- and -after comparisons in the study unit also showed a significantly reduced percentage of total opportunities for error ( 20.4 % and 13.5 % ; p < .01 ) . An analysis of detailed opportunities for error showed a significant impact of the automated dispensing system in reducing preparation errors ( p < .05 ) . Most errors caused no harm ( National Coordinating Council for Medication Error Reporting and Prevention category C ) . The automated dispensing system did not reduce errors causing harm . Finally , the mean for working conditions improved from 1.0 ± 0.8 to 2.5 ± 0.8 on the four-point Likert scale . Conclusions : The implementation of an automated dispensing system reduced overall medication errors related to picking , preparation , and administration of drugs in the intensive care unit . Furthermore , most nurses favored the new drug dispensation organization Automated medication distribution systems have helped solve issues of efficiency and effectiveness . Cost-benefit analysis conducted by nursing and pharmacy departments can help to objectify the decision to adopt this technology PURPOSE The results of the 2014 ASHP national survey of pharmacy practice in hospital setting s that pertain to dispensing and administration are described . METHODS A stratified r and om sample of pharmacy directors at 1435 general and children 's medical-surgical hospitals in the United States were surveyed by mail . RESULTS In this national probability sample survey , the response rate was 29.7 % . Ninety-seven percent of hospitals used automated dispensing cabinets in their medication distribution systems , 65.7 % of which used individually secured lidded pockets as the predominant configuration . Overall , 44.8 % of hospitals used some form of machine-readable coding to verify doses before dispensing in the pharmacy . Overall , 65 % of hospital pharmacy departments reported having a cleanroom compliant with United States Pharmacopeia chapter 797 . Pharmacists review ed and approved all medication orders before the first dose was administered , either onsite or by remote order view , except in procedure areas and emergency situations , in 81.2 % of hospitals . Adoption rates of electronic health information have rapidly increased , with the widespread use of electronic health records , computer prescriber order entry , barcodes , and smart pumps . Overall , 31.4 % of hospitals had pharmacists practicing in ambulatory or primary care clinics . Transitions-of-care services offered by the pharmacy department have generally increased since 2012 . Discharge prescription services increased from 11.8 % of hospitals in 2012 to 21.5 % in 2014 . Approximately 15 % of hospitals out source d pharmacy management operations to a contract pharmacy services provider , an increase from 8 % in 2011 . CONCLUSION Health-system pharmacists continue to have a positive impact on improving healthcare through programs that improve the efficiency , safety , and clinical outcomes of medication use in health systems Output:

It appears that ADDs were effective in reducing medication storage errors and the time that nurses spent taking inventory of narcotics and controlled substances . There was no definitive evidence that using ADDs increased the time that nurses or pharmacists spent with patients , reduced medication errors result ing in patient harm , or reduced costs in Canadian hospitals . However , pharmacy technicians spent more time stocking the machines . ADDs have limited potential to decrease medication errors and increase efficiencies , but their impact is highly institution-specific , and use of this technology requires proper integration into an institution 's medication distribution process .

MS214127

***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 the study was to evaluate the effectiveness of functional progressive resistance exercise ( PRE ) training on walking ability in children with cerebral palsy ( CP ) . Fifty-one ambulant children with spastic CP ( mean age 10 years 5 months , 29 boys ) were r and omized to an intervention ( n=26 ) or control group ( n=25 , receiving usual care ) . The intervention consisted of 12 weeks functional PRE circuit training , for 3 times a week . Main outcome measures were walking ability and participation . Secondary outcomes were muscle strength and anaerobic muscle power . Possible adverse outcomes were spasticity and passive range of motion ( ROM ) . Muscle strength increased significantly in the training group compared to the control group , but walking ability , participation and anaerobic muscle power did not change . Spasticity and ROM remained unchanged , except for a significant decrease in rectus femoris length in the intervention group . It is concluded that twelve weeks of functional PRE-training does not improve walking ability , despite improved muscle strength AIM The aim of this study was to investigate whether individualized resistance training improves the physical mobility of young people with cerebral palsy ( CP ) . METHOD Forty-eight participants with spastic diplegic CP ( 26 males , 22 females ; mean age 18y 1mo , SD 1y 11mo ) classified as level II or III on the Gross Motor Function Classification System were allocated r and omly to progressive resistance training or usual-care control . Resistance training was completed twice weekly for 12 weeks at a community gymnasium under the supervision of a physiotherapist . Exercises were based on instrumented gait analysis and targeted muscles contributing to walking difficulties . Outcomes at 12 weeks and 24 weeks included objective measures of mobility ( 6-min walk test , instrumented gait analysis , and Gross Motor Function Measure dimensions D and E ) , participant-rated measures of mobility ( Functional Mobility Scale and Functional Assessment Question naire ) , and muscle performance . RESULTS The strength of targeted muscles increased by 27 % ( 95 % CI 8 - 46 % ) compared with control group . There were no between-group differences in any objective measure of mobility at 12 weeks ( 6-min walk test : mean difference 0.1 m ; 95 % CI -21 to 21 m ) or at 24 weeks . Participant-rated mobility improved ( Functional Mobility Scale at 5 m : mean 0.6 units ; 95 % CI 0.1 - 1.1 units ; Functional Assessment Question naire : 0.8 units ; 95 % CI 0.1 - 1.6 units ) compared with control group at 12 weeks . INTERPRETATION Individualized progressive resistance training increased strength in adolescents and young adults with spastic diplegic CP . Despite participant-rated benefits , the increased strength did not result in objective improvements in mobility AIM The aim of the present study was to assess and compare the improvements of muscle strength and power induced by a 16-week resistive programme in a population of 16 older men aged 65 - 81 years . METHODS Training was performed three times per week at an intensity of 80 % of one repetition maximum ( 1RM ) and consisted of both calf raise and leg press exercises . Before- , during- and after-training , maximum isometric and isokinetic torques , maximum power , 1RM , muscle cross-sectional area ( CSA ) and electromyographic activity ( EMG ) of the plantar flexors ( PF ) and knee extensors ( KE ) were examined . RESULTS For the KE and PF , respectively , training result ed in a 29.9 + /- 4.4 % ( mean + /- SE ) and 21.6 + /- 5.4 % increase in 1RM ( P < 0.001 - 0.01 ) , a 19.4 + /- 4.3 and 12.4 + /- 4.7 % ( P < 0.001 - 0.05 ) increase in maximum isometric torque , and a 24.1 + /- 6.3 and 33.1 + /- 10.9 % ( P < 0.05 ) increase in maximum muscle power , calculated from torque-angular velocity curves . The large increase in torque and power was partly accounted by a significant increase in the CSA of the PF ( 5.0 + /- 0.7 % ) and KE ( 7.4 + /- 0.7 % ) , while no significant changes in integrated EMG activity of vastus lateralis and soleus muscles , and in extrapolated maximum shortening velocity were found . After training , a significant increase in torque/CSA ( 10.3 + /- 4 % , P < 0.05 ) was found for the KE but not for the PF . CONCLUSION Hence , hypertrophy can not alone justify the increase in torque , and other factors , such as an increase in individual fibre-specific tension ( in the case of KE ) , a decrease in antagonist muscles ' coactivation , an improved co-ordination and an increased neural drive of the other heads of quadriceps may have contributed to the increments in strength . The significant increase in muscle power seems particularly noteworthy with respect to daily activities involving the displacement of the body over time , namely , the generation of muscle power Abstract The aims of this study were to assess changes in muscle architecture , isometric and dynamic strength of the leg extensor muscles , result ing from dynamic resistance training , and the relationships between strength and muscle architecture variables . The participants ( n = 30 ) were r and omly assigned to one of two groups . The training group ( n = 16 ; age 21.8 ± 2.3 years , body mass 74.8 ± 9.2 kg , height 1.75 ± 0.08 m ) performed dynamic resistance training for 13 weeks . The control group ( n = 14 ; age 19.9 ± 1.5 years , body mass 74.0 ± 8.5 kg , height 1.76 ± 0.05 m ) did not perform any resistance training . Maximal dynamic and isometric strength were tested in both groups , before and after the training period . The members of the training group used the free-weight squat lift ( 90 ° ) as their training exercise . The concentric phase of the squat was performed explosively . Skeletal muscle architecture of the vastus lateralis was visualized using ultrasonography . At the end of the study , significant increases in vastus lateralis muscle thickness ( + 6.9 % , P < 0.001 ) , fascicle length ( + 10.3 % , P < 0.05 ) , one-repetition maximum ( + 8.2 % , P < 0.05 ) , rate of force development ( + 23.8 % , P < 0.05 ) and average force produced in the first 500 ms ( + 11.7 % , P < 0.05 ) were seen only in the training group . Adaptations to the muscle architecture in the training group limited the loss of fibre force , and improved the capacity for developing higher velocities of contraction . The architectural changes in the training group were similar to those seen in studies where high-speed training was performed . In conclusion , dynamic resistance training with light loads leads to increases in muscle thickness and fascicle length , which might be related to a more efficient transmission of fibre force to the tendon BACKGROUND Fascicle length and fascicle excursion measurements in children with cerebral palsy have yielded inconsistent results . The purpose of this study was to measure in vivo passive fascicle lengths and fascicle excursions in the Medial Gastrocnemius muscle of children with cerebral palsy and typically developing controls . METHODS We measured 11 children with spastic cerebral palsy and 14 controls between the ages of 9 and 16years . Ultrasound imaging was used to measure fascicle lengths while a dynamometer moved the ankle joint through the range of motion . A common range of motion for all subjects was used for analysis of fascicle excursion . FINDINGS Fascicle lengths in children with cerebral palsy were 43 % smaller than those for control subjects throughout the range of motion . The relative fascicle excursion was 92 % greater on average for the cerebral palsy compared to the control group children . The muscle excursion for the control group children was greater than for the cerebral palsy group children . INTERPRETATION Since the fascicles in children with spastic cerebral palsy are shorter , but they go through the same excursion as fascicles in typically developing children , sarcomeres within the medial gastrocnemius muscle must be working over a larger range of sarcomere lengths . Combined with findings of overstretched sarcomeres in spastic muscles reported in the literature , our results suggest that the increased passive forces and the weakness found in spastic muscles may be caused by a decrease in contractile filament overlap as sarcomeres are pulled to extreme lengths in children with cerebral palsy Background . Everyday activities for youth with cerebral palsy ( CP ) require muscle power , but the velocity component of muscle contraction is neglected with traditional strength training ( ST ) . Objective . To determine whether velocity training ( VT ) , which includes resistance training at increasingly higher velocities , would induce specific muscle adaptations not observed with ST . Methods . Sixteen ambulatory youth with CP were r and omized to VT or ST . Participants trained the knee extensors 3 times per week for 24 sessions on a Biodex dynamometer . At each session , 6 sets of 5 concentric repetitions were performed either at 30 deg/s ( ST group ) or progressively higher velocities from 30 deg/s to 120 deg/s ( VT group ) . Outcomes included muscle architecture , power , strength , walking speed , and functional walking performance . Results . A significant increase in rectus femoris fascicle length was observed after VT with a decrease after ST . Rectus femoris cross-sectional area increased in both groups . Both showed significant increases in isokinetic strength at all tested speeds ; however , peak velocity and power improved after VT only . Self-selected and fast walking speed and functional walking performance improved after VT only . Conclusions . Muscle architecture in CP is capable of adapting differentially to the training stimulus . VT was equally effective as traditional ST in improving isokinetic strength of the knee extensors but more effective in improving velocity of movement , muscle power , and walking performance . Differences may be partially attributed to specificity of training effects on muscle architecture , such as the increase in fascicle length after VT . Strengthening interventions involving higher velocity movements should be incorporated into clinical practice Background . To date , no reports have investigated neuromuscular electrical stimulation ( NMES ) to increase muscle force production of children with cerebral palsy ( CP ) using high-force contractions and low repetitions . Objective . The aims of this study were to determine if isometric NMES or volitional training in children with CP could increase muscle strength and walking speed and to examine the mechanisms that may contribute to increased force production . Methods . Eleven children with spastic diplegia were assigned to an NMES training group or to a volitional training group . Participants in the NMES group had electrodes implanted percutaneously to activate the quadriceps femoris and triceps surae muscles . The volitional group trained with maximal effort contractions . Both groups performed a 12-week isometric strength-training program . Maximum voluntary isometric contraction ( MVIC ) force , voluntary muscle activation , quadriceps and triceps surae cross-sectional area ( CSA ) , and walking speed were measured pre- and post-strength training . Results . The NMEStrained group had greater increases in normalized force production for both the quadriceps femoris and triceps surae . Similarly , only the NMES group showed an increase in walking speed after training . Changes in voluntary muscle activation explained approximately 67 % and 37 % of the changes seen in the MVIC of the NMES and volitional groups , respectively . Quadriceps femoris maximum CSA increased significantly for the NMES group only . Conclusions . This study was the first to quantitatively show strength gains with the use of NMES in children with CP . These results support the need for future experimental studies that will examine the clinical effectiveness of NMES strength training 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 o Output:

A large effect was found on muscle cross-sectional area following strength training , with small to moderate effects on muscle volume and thickness . CONCLUSION AND IMPLICATION S There is preliminary evidence that strength training leads to hypertrophy in children and adolescents with CP . A paucity of studies exist measuring morphological and architectural parameters following strength training in these individuals .

MS214128

***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 This study examined the role of behavioral and material factors in explaining educational differences in all-cause mortality , taking into account the overlap between both types of factors . METHODS Prospect i ve data were used on 15,451 participants in a Dutch longitudinal study . Relative hazards of all-cause mortality by educational level were calculated before and after adjustment for behavioral factors ( alcohol intake , smoking , body mass index , physical activity , dietary habits ) and material factors ( financial problems , neighborhood conditions , housing conditions , crowding , employment status , a proxy of income ) . RESULTS Mortality was higher in lower educational groups . Four behavioral factors ( alcohol , smoking , body mass index , physical activity ) and 3 material factors ( financial problems , employment status , income proxy ) explained part of the educational differences in mortality . With the overlap between both types of factors accounted for , material factors were more important than behavioral factors in explaining mortality differences by educational level . CONCLUSIONS The association between educational level and mortality can be largely explained by material factors . Thus , improving the material situation of people might substantially reduce educational differences in mortality A r and omised control trial evaluated the effectiveness of a theory-based persuasive leaflet design ed to encourage students to undertake at least one additional physical exercise session a week . Participants were 503 secondary school students attending a school in South-East Engl and . The leaflet was written to target potentially modifiable cognitive antecedents of exercise specified by the Theory of Planned Behaviour . It was separately augmented with two cognitive change techniques , result ing in three intervention conditions , leaflet alone ; leaflet plus motivational quiz , and leaflet plus implementation intention prompt , as well as a no-leaflet control condition . Cognitions and behaviour were measured immediately before and 3 weeks after intervention . The results showed that all three-leaflet interventions significantly increased reported exercise , intention to exercise and related cognitions , compared to the control condition , but did not differ in their impact . Mediation analysis showed that intervention effects on exercise were partially mediated by intentions and perceived behavioural control OBJECTIVE : To evaluate the 6-month impact of a physical activity ( PA ) multilevel intervention on activity patterns and psychological predictors of PA among adolescents . The intervention was directed at changing knowledge and attitudes and at providing social support and environmental conditions that encourage PA of adolescents inside and outside school . SUBJECTS AND DESIGN : R and omised , controlled ongoing field trial ( ICAPS ) in middle-school 's first-level adolescents from eight schools selected in the department of the Bas-Rhin ( Eastern France ) with a cohort of 954 adolescents ( 92 % of the eligible students ) initially aged 11.7±0.6 y. The 6-month changes in participation in leisure organised PA ( LOPA ) , high sedentary ( SED ) behaviour ( > 3h/day ) , self-efficacy ( SELF ) and intention ( INTENT ) towards PA were analysed after controlling for baseline measures and different covariables ( age , overweight , socioprofessional occupation ) , taking into account the cluster r and omisation design . RESULTS : The proportion of intervention adolescents not engaged in organised PA was reduced by 50 % whereas it was unchanged among control students . After adjustment for baseline covariables , LOPA participation significantly increased among the intervention adolescents ( odds ratio ( 95 % confidence interval ) (OR)=3.38 ( 1.42–8.05 ) in girls ; 1.73 ( 1.12–2.66 ) in boys ) , while high SED was reduced ( OR=0.54 ( 0.38–0.77 ) in girls ; 0.52 ( 0.35–0.76 ) in boys ) . The intervention improved SELF in girls , whatever their baseline LOPA ( P<10−4 ) and INTENT in girls with no baseline LOPA ( P=0.04 ) . SELF tended to improve in boys with no baseline LOPA , without reaching statistical significance . When included in the regression , follow-up LOPA was associated with improvement of SELF in girls ( P=0.02 ) and of INTENT in girls with no baseline PA ( P<0.02 ) . The intervention effect was then attenuated . CONCLUSION : After 6 months of intervention , ICAPS was associated with a significant improvement of activity patterns and psychological predictors , indicating a promising approach for modifying the long-term PA level of adolescents BACKGROUND The aim of this study was to investigate stability of physical activity from childhood and adolescence to adulthood in multiple age cohorts , and analyze how well adult physical activity can be predicted by various physical activity variables measured in childhood and adolescence . METHODS The data were drawn from the Cardiovascular Risk in Young Finns Study . The study was started in 1980 , when cohorts of r and omly sample d boys and girls aged 3 , 6 , 9 , 12 , 15 , and 18 years ( total of 2309 subjects ) were examined for the first time . The measurements were repeated in 1983 , 1986 , 1989 , 1992 , and 2001 . In 2001 , the subjects ( n = 1563 , 68 % ) were aged 24 , 27 , 30 , 33 , 36 , and 39 years , respectively . Physical activity was measured by means of a short self-report question naire that was administered individually in connection with a medical examination . On the basis of a question naire , a physical activity index ( PAI ) was calculated . There were no significant differences in the 1980 PAI between participants and dropouts in 2001 . RESULTS Spearmans rank order correlation coefficients for the 21-year tracking period varied from 0.33 to 0.44 in males , and from 0.14 to 0.26 in females . At shorter time intervals the correlation was higher . On average , the tracking correlation was lower in females than in males . Persistent physical activity , defined as a score in the most active third of the PAI in two or three consecutive measurements , increased the odds that an individual would be active in adulthood . Odds ratios for 3-year continuous activity versus continuous inactivity varied from 4.30 to 7.10 in males and 2.90 to 5.60 in females . The corresponding odds ratios for 6-year persistence were 8.70 to 10.80 and 5.90 to 9.40 . CONCLUSIONS It was concluded that a high level of physical activity at ages 9 to 18 , especially when continuous , significantly predicted a high level of adult physical activity . Although the correlations were low or moderate , we consider it important that school-age physical activity appears to influence adult physical activity , and through it , the public health of the general population OBJECTIVES ICAPS ( Intervention Centred on Adolescents ' Physical activity and Sedentary behaviour ) is aim ed at preventing excessive weight gain and cardiovascular risk in adolescents by promoting physical activity ( PA ) with an emphasis on recreational and daily-life PA , with a lifelong perspective . DESIGN R and omized study design ed to last for four years . Study cohort constituted of 954 first-level students ( 91 % of eligible pupils ) , aged 11.7 + /- 0.6 y ( mean + /- SD ) from four pairs of schools r and omly selected in eastern France , after sociogeographical stratification . In each pair , intervention status was r and omised at school-level . The program , not limited to school setting s , involves multiple partners with three objectives : 1 ) changing attitudes through debates and access to attractive activities during breaks and after-school hours , 2 ) encouraging social support , 3 ) providing environmental conditions that enable PA . Adapted times and places , open participation , emphasis on fun , meeting with others and absence of competitive aspects are used to reduce usual barriers to PA . Accessibility and safety are permanent concerns . RESULTS Prevalence of overweight was 23.7 % . High participation rates were attained ( 50 % participated in at least one weekly activity ) . At six-month , the proportion of intervention adolescents not performing supervised PA out of academic PA was reduced by half ( 36 % to 17 % vs 42 % to 42 % in controls P < 10 - 4 ) ; the proportion of those spending > 3 h/day in sedentary occupations decreased ( 34 % to 28 % vs 27 % to 36 % ; P < 10 - 4 ) . CONCLUSION These data demonstrate the feasibility of implementing a multilevel PA intervention program in adolescents . Six-month results document increased PA and decreased sedentary behaviour Abstract Objectives : To evaluate the effectiveness of inviting teenagers to general practice consultations to discuss health behaviour concerns and appropriate follow up care . Design : R and omised controlled trial , with participants r and omised to a consultation ( intervention ) or usual care ( control ) . Question naires completed at baseline , 3 months , and 12 months . Setting : Eight general practice s in Hertfordshire , Engl and . Participants : 1516 teenagers aged 14 - 15 years . Intervention : Consultations with practice nurses to discuss health concerns and develop plans for healthier lifestyles . Main outcome measures : Mental and physical health , “ stage of change ” for health related behaviour , and use of health services . Results : At baseline 970 teenagers completed question naires ; 23 % smoked , 35 % had been drunk in the previous three months , 64 % considered they ate unhealthily , 39 % took little exercise , and 36 % had possible depression . 41 % ( 304 ) of teenagers invited attended for a consultation ; over one third ( 112 ) were offered follow up care . More intervention group teenagers reported positive movement in stage of change for diet and exercise and in at least one of four behaviours ( diet , exercise , smoking , drinking alcohol ) at 3 months ( 41 % v 31 % , P<0.01 ) , but this did not persist at 12 months . There was marginally more positive change in actual behaviour by intervention teenagers at 3 months ( 16 % v 12 % , P=0.06 ) . Recognition of possible depression result ed in improved mental health outcomes at 3 and 12 months . 97 % of attenders said they would recommend the intervention to a friend . Conclusions : Change in behaviour was slight but encouraging , and the intervention was well received and relatively cheap Interventions to promote physical activity are important in preventing children from becoming overweight . Many projects have been developed but only a few showed ( moderate ) effects . JUMP-in is a systematic ally developed primary -school-based intervention that focuses on the use of theory , environmental changes , parental influences and cooperation with multi-level parties in intervention development . The effects of JUMP-in were evaluated with a quasi-experimental pre-test/post-test research design . In total , 510 children from Grade s 4 , 5 and 6 of four intervention schools and two control schools in Amsterdam were followed for an intervention period of one school year . Changes in physical activity as well as in the social cognitive determinants were assessed using self-reports . In addition , a process evaluation has been executed . The results show that JUMP-in was effective in influencing physical activity , especially among children from Grade 6 . Children in the control group decreased their level of physical activity considerably , while activity levels in intervention children from Grade 6 remained stable . The intervention effects could not be explained by changes in the measured social cognitive determinants . In contrast , process information illuminated differences in intervention effects between the participating schools . The results from the JUMP-in study show the importance of intervention design s that focus on a theory-based mix of relevant environmental and social cognitive factors Physical activity levels in young adults are low . Research supports the use of the Transtheoretical Model of behaviour change ( TM ) in design ing physical activity interventions . This study used a pre-post r and omized control design to investigate the effectiveness of a self-instructional intervention for helping sedentary young adults to initiate physical activity . Post-intervention , significantly more of the experimental group ( 80 % ) , in comparison to the control group ( 68 % ) , improved their exercise stage of change ( SOC ) from baseline ( P < 0.05 ) . Discriminant analyses revealed that discrimination between stage improvement/non-improvement was possible using the processes of change data . Stage improvers scored significantly higher on all of the behavioral and four out of five of the cognitive processes of change . For stage improvers , the processes of self-re-evaluation and self-liberation were most frequently used , whilst social liberation was used significantly more by the experimental than the control group . This inexpensive , self-instructional intervention , based on the TM and the ' active living message ' , is an effective method of assisting sedentary young adults to progress through the exercise SOC Low levels of physical activity coupled with high levels of television viewing have been linked with obesity in children . The objective of this study was to assess the efficacy of ' Switch Off-Get Active ' , a 16-week controlled health education intervention , in increasing physical activity and reducing screen time and BMI in primary school children . A secondary objective was to compare children with high and low screen time . Participants were 312 children aged 10.2+/-0.7 years , attending nine schools in areas of social disadvantage . The 10-lesson , teacher-led intervention , conducted in spring 2003 , emphasised self-monitoring , budgeting of time and selective viewing . Differences , adjusted for baseline values by ANCOVA , existed between intervention and control children at follow-up for self-reported physical activity ( intervention + 0.84 30 min blocks/day , 95%CI 0.11 - 1.57 , p<0.05 ) and self-efficacy for physical activity ( p<0.05 ) but not self-reported screen time ( intervention--0.41 blocks/day , 95%CI--0.93 - 0.12 Output:

Main findings of the review were : ( 1 ) school-based interventions generally lead to short term improvements in physical activity levels ; ( 2 ) improvements in physical activity levels by school-based interventions were limited to school related physical activity with no conclusive transfer to leisure time physical activity ; ( 3 ) including parents appeared to enhance school-based interventions ; ( 4 ) the support of peers and the influence of direct environmental changes increased the physical activity level of secondary school children ; ( 5 ) the assumption that a multi-component approach should produce synergistic results can not be confirmed ; ( 6 ) when interventions aim ed to affect more than one health behaviour the intervention appeared to be less effective in favour of physical activity . Conclusion Overall , the current European literature supports the short-term effectiveness of school-based physical activity promotion programmes .

MS214129

***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 investigate the efficacy of a novel brain plasticity-based computerized cognitive training program in older adults and to evaluate the effect on untrained measures of memory and attention and participant-reported outcomes . DESIGN Multisite r and omized controlled double-blind trial with two treatment groups . SETTING Communities in northern and southern California and Minnesota . PARTICIPANTS Community-dwelling adults aged 65 and older ( N=487 ) without a diagnosis of clinical ly significant cognitive impairment . INTERVENTION Participants were r and omized to receive a broadly-available brain plasticity-based computerized cognitive training program ( intervention ) or a novelty- and intensity-matched general cognitive stimulation program modeling treatment as usual ( active control ) . Duration of training was 1 hour per day , 5 days per week , for 8 weeks , for a total of 40 hours . MEASUREMENTS The primary outcome was a composite score calculated from six subtests of the Repeatable Battery for the Assessment of Neuropsychological Status that use the auditory modality ( RBANS Auditory Memory/Attention ) . Secondary measures were derived from performance on the experimental program , st and ardized neuropsychological assessment s of memory and attention , and participant-reported outcomes . RESULTS RBANS Auditory Memory/Attention improvement was significantly greater ( P=.02 ) in the experimental group ( 3.9 points , 95 % confidence interval (CI)=2.7 - 5.1 ) than in the control group ( 1.8 points , 95 % CI=0.6 - 3.0 ) . Multiple secondary measures of memory and attention showed significantly greater improvements in the experimental group ( word list total score , word list delayed recall , digits backwards , letter-number sequencing ; P<.05 ) , as did the participant-reported outcome measure ( P=.001 ) . No advantage for the experimental group was seen in narrative memory . CONCLUSION The experimental program improved generalized measures of memory and attention more than an active control program OBJECTIVE This study evaluates the efficacy at 12 months of a computer-based cognitive training ( CBCT ) program , adjunctive to traditional cognitive training ( TCT ) , on the basis of pen- and -paper exercises . METHODS Sixty patients with multi-domain mild cognitive impairment and mild Alzheimer 's disease who were already receiving cognitive training , recruited from a day hospital , were assigned into two groups following a simple r and omization procedure ( computerized r and om numbers ) : ( i ) a group that received CBCT during 3 months and TCT ( CBCT + TCT ) , n = 37 , and ( ii ) a group that received only TCT , n = 23 . Patients were assessed at baseline and after 3 and 12 months of treatment by a neuropsychologist blinded to group assignment , with a neuropsychological battery ( primary outcomes ) and measures of decision making , memory complaints , and emotional disturbances . RESULTS With the use of repeated- measures analyses of covariance , the CBCT + TCT group showed less anxiety symptoms ( F = 5.13 , p = 0.03 , d = 1.12 ) and less disadvantageous choices ( F = 4.70 , p = 0.04 , d = 0.89 ) in decision making than the TCT group at 12 months . No significant improvement or worsening was observed in the other measures examined . However , positive effect sizes favoring the CBCT + TCT group were observed in all variables . CONCLUSIONS The addition of a CBCT program was effective in anxiety and decision making but had no significant effects on outcomes in basic cognitive functions in patients who were already receiving cognitive training , possibly due to a ceiling effect . Future studies should compare the efficacy of CBCT with TCT in naïve patients Does the structure of an adult human brain alter in response to environmental dem and s ? Here we use whole-brain magnetic-resonance imaging to visualize learning-induced plasticity in the brains of volunteers who have learned to juggle . We find that these individuals show a transient and selective structural change in brain areas that are associated with the processing and storage of complex visual motion . This discovery of a stimulus-dependent alteration in the brain 's macroscopic structure contradicts the traditionally held view that cortical plasticity is associated with functional rather than anatomical changes BACKGROUND Dementia cases may reach 100 million by 2050 . Interventions are sought to curb or prevent cognitive decline . Exercise yields cognitive benefits , but few older adults exercise . Virtual reality-enhanced exercise or " exergames " may elicit greater participation . PURPOSE To test the following hypotheses : ( 1 ) stationary cycling with virtual reality tours ( " cybercycle " ) will enhance executive function and clinical status more than traditional exercise ; ( 2 ) exercise effort will explain improvement ; and ( 3 ) brain-derived neurotrophic growth factor ( BDNF ) will increase . DESIGN Multi-site cluster r and omized clinical trial ( RCT ) of the impact of 3 months of cybercycling versus traditional exercise , on cognitive function in older adults . Data were collected in 2008 - 2010 ; analyses were conducted in 2010 - 2011 . SETTING / PARTICIPANTS 102 older adults from eight retirement communities enrolled ; 79 were r and omized and 63 completed . INTERVENTIONS A recumbent stationary ergometer was utilized ; virtual reality tours and competitors were enabled on the cybercycle . MAIN OUTCOME MEASURES Executive function ( Color Trails Difference , Stroop C , Digits Backward ) ; clinical status ( mild cognitive impairment ; MCI ) ; exercise effort/fitness ; and plasma BDNF . RESULTS Intent-to-treat analyses , controlling for age , education , and cluster r and omization , revealed a significant group X time interaction for composite executive function ( p=0.002 ) . Cybercycling yielded a medium effect over traditional exercise ( d=0.50 ) . Cybercyclists had a 23 % relative risk reduction in clinical progression to MCI . Exercise effort and fitness were comparable , suggesting another underlying mechanism . A significant group X time interaction for BDNF ( p=0.05 ) indicated enhanced neuroplasticity among cybercyclists . CONCLUSIONS Cybercycling older adults achieved better cognitive function than traditional exercisers , for the same effort , suggesting that simultaneous cognitive and physical exercise has greater potential for preventing cognitive decline . TRIAL REGISTRATION This study is registered at Clinical trials.gov NCT01167400 Objective : To determine the usefulness of an interactive multimedia internet-based system ( IMIS ) for the cognitive stimulation of Alzheimer ’s disease . Methods : This is a 24-week , single-blind , r and omised pilot study conducted on 46 mildly impaired patients suspected of having Alzheimer ’s disease receiving stable treatment with cholinesterase inhibitors ( ChEIs ) . The patients were divided into three groups : ( 1 ) those who received 3 weekly , 20-min sessions of IMIS in addition to 8 h/day of an integrated psychostimulation program ( IPP ) ; ( 2 ) those who received only IPP sessions ; and ( 3 ) those who received only ChEI treatment . The primary outcome measure was the Alzheimer ’s Disease Assessment Scale-Cognitive ( ADAS-Cog ) . Secondary outcome measures were : Mini-Mental State Examination ( MMSE ) , Syndrom Kurztest , Boston Naming Test , Verbal Fluency , and the Rivermead Behavioral Memory Test story recall subtest . Results : After 12 weeks , the patients treated with both IMIS and IPP had improved outcome scores on the ADAS-Cog and MMSE , which was maintained through 24 weeks of follow-up . The patients treated with IPP alone had better outcome than those treated with ChEIs alone , but the effects were attenuated after 24 weeks . All patients had improved scores in all of the IMIS individual tasks , attaining higher levels of difficulty in all cases . Conclusion : Although both the IPP and IMIS improved cognition in patients with Alzheimer ’s disease , the IMIS program provided an improvement above and beyond that seen with IPP alone , which lasted for 24 weeks We performed a pilot r and omized , controlled trial of intensive , computer-based cognitive training in 47 subjects with mild cognitive impairment . The intervention group performed exercises specifically design ed to improve auditory processing speed and accuracy for 100 min/d , 5 d/wk for 6 weeks ; the control group performed more passive computer activities ( reading , listening , visuospatial game ) for similar amounts of time . Subjects had a mean age of 74 years and 60 % were men ; 77 % successfully completed training . On our primary outcome , Repeatable Battery for Assessment of Neuropsychological Status total scores improved 0.36 st and ard deviations ( SD ) in the intervention group ( P=0.097 ) compared with 0.03 SD in the control group ( P=0.88 ) for a nonsignificant difference between the groups of 0.33 SD ( P=0.26 ) . On 12 secondary outcome measures , most differences between the groups were not statistically significant . However , we observed a pattern in which effect sizes for verbal learning and memory measures tended to favor the intervention group whereas effect sizes for language and visuospatial function measures tended to favor the control group , which raises the possibility that these training programs may have domain-specific effects . We conclude that intensive , computer-based mental activity is feasible in subjects with mild cognitive impairment and that larger trials are warranted Despite the growing interest in cognitive training programs as a potential non-pharmacological approach to slowing cognitive decline in mild cognitive impairment ( MCI ) , there has been little research on the differential effectiveness of training among subtypes of MCI ( i.e. , amnestic , single non-amnestic , and multi-domain ) . The current study examined the longitudinal effects of cognitive speed of processing training ( SOPT ) among older adults with psychometricallydefined MCI from the Advanced Cognitive Training for Independent and Vital Elderly ( ACTIVE ) trial . Mixed model ANOVAs examined the effectiveness of SOPT in participants with MCI relative to controls and also compared training effectiveness in MCI subgroups to appropriate controls . A mixed effects model compared SOPT training effects longitudinally across five years relative to controls . A second mixed effects model compared the durability of training gains between the MCI subtypes across 5 years . All subtypes of MCI showed immediate improvement post-training relative to controls , with the single non-amnestic subtype showing the most benefit . Additionally , all subtypes showed similar trajectories across five years . There were no significant changes in performance across time , indicating initial training gains were maintained . These results provide support for the effectiveness and potential durability of SOPT among persons with MCI regardless of subtype . Future research should investigate if SOPT transfers to improvements in the everyday functioning of those with MCI A r and omized pilot experiment examined the neural substrates of response to cognitive training in participants with mild cognitive impairment ( MCI ) . Participants performed exercises previously demonstrated to improve verbal memory and an active control group performed other computer activities . An auditory-verbal fMRI task was conducted before and after the two-month training program . Verbal memory scores improved significantly and left hippocampal activation increased significantly in the experimental group ( gains in 5 of 6 participants ) relative to the control group ( reductions in all 6 participants ) . Results suggest that the hippocampus in MCI may retain sufficient neuroplasticity to benefit from cognitive training 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 extent to which mental and physical exercise may slow cognitive decline in adults with early signs of cognitive impairment is unknown . This article provides the rationale and methodology of the first trial to investigate the isolated and combined effects of cognitive training ( CT ) and progressive resistance training ( PRT ) on general cognitive function and functional independence in older adults with early cognitive impairment : Study of Mental and Regular Training ( SMART ) . Our secondary aim is to quantify the differential adaptations to these interventions in terms of brain morphology and function , cardiovascular and metabolic function , exercise capacity , psychological state and body composition , to identify the potential mechanisms of benefit and broader health status effects . Methods SMART is a double-blind r and omized , double sham-controlled trial . One hundred and thirty-two community-dwelling volunteers will be recruited . Primary inclusion criteria are : at risk for cognitive decline as defined by neuropsychology assessment , low physical activity levels , stable disease , and age over 55 years . The two active interventions are computerized CT and whole body , high intensity PRT . The two sham interventions are educational videos and seated calisthenics . Participants are r and omized into 1 of 4 supervised training groups ( 2 d/wk × 6 mo ) in a fully factorial design . Primary outcomes measured at baseline , 6 , and 18 months are the Alzheimer 's Disease Assessment Scale ( ADAS-Cog ) , neuropsychological test scores , and Bayer Informant Instrumental Activities of Daily Living ( B-IADLs ) . Secondary outcomes are psychological well-being , quality of life , cardiovascular and musculoskeletal function , body composition , insulin resistance , systemic inflammation and anabolic/neurotrophic hormones , and brain morphology and function via Magnetic Resonance Imaging ( MRI ) and Spectroscopy ( fMRS ) . Discussion SMART will provide a novel evaluation of the immediate and long term benefits of CT , PRT , and combined CT and PRT on global cognitive function and brain morphology , as well as potential underlying mechanisms of adaptation in older adults at risk of further cognitive decline . Trial Registration Australia and New Zeal and Clinical Trials Register ( ANZCTR ) : CONTEXT Cognitive function in older adult Output:

The cognitive domains of attention , executive function , and memory ( visual and verbal ) showed the most consistent improvements . CCT and V RCT were moderately effective in long-term improvement of cognition for those at high risk of cognitive decline . Total intervention time did not mediate efficacy .

MS214130

***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 exercise has been shown to relieve depression , little is known about its mechanism or dose-response characteristics . We hypothesized that high intensity progressive resistance training ( PRT ) would be more effective than either low intensity PRT or st and ard care by a general practitioner ( GP ) in depressed elderly persons , and that high intensity PRT would provide superior benefits in quality of life , sleep quality , and self-efficacy . METHODS Sixty community-dwelling adults > 60 years with major or minor depression were r and omized to supervised high intensity PRT ( 80 % maximum load ) or low intensity PRT ( 20 % maximum load ) 3 days per week for 8 weeks , or GP care . RESULTS A 50 % reduction in the Hamilton Rating Scale of Depression score was achieved in 61 % of the high intensity , 29 % of the low intensity , and 21 % of the GP care group ( p = .03 ) . Strength gain was directly associated with reduction in depressive symptoms ( r = 0.40 , p = .004 ) , as was baseline social support network type ( F = 3.52 , p = .015 ) , whereas personality type , self-efficacy , and locus of control were unrelated to the antidepressant effect . Vitality quality -of-life scale improved more in the high intensity group than in the others ( p = .04 ) . Sleep quality improved significantly in all participants ( p < .0001 ) , with the greatest relative change in high intensity PRT ( p = .05 ) . CONCLUSIONS High intensity PRT is more effective than is low intensity PRT or GP care for the treatment of older depressed patients BACKGROUND Previous observational and interventional studies have suggested that regular physical exercise may be associated with reduced symptoms of depression . However , the extent to which exercise training may reduce depressive symptoms in older patients with major depressive disorder ( MDD ) has not been systematic ally evaluated . OBJECTIVE To assess the effectiveness of an aerobic exercise program compared with st and ard medication ( ie , antidepressants ) for treatment of MDD in older patients , we conducted a 16-week r and omized controlled trial . METHODS One hundred fifty-six men and women with MDD ( age , > or = 50 years ) were assigned r and omly to a program of aerobic exercise , antidepressants ( sertraline hydrochloride ) , or combined exercise and medication . Subjects underwent comprehensive evaluations of depression , including the presence and severity of MDD using Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition criteria and Hamilton Rating Scale for Depression ( HAM-D ) and Beck Depression Inventory ( BDI ) scores before and after treatment . Secondary outcome measures included aerobic capacity , life satisfaction , self-esteem , anxiety , and dysfunctional cognitions . RESULTS After 16 weeks of treatment , the groups did not differ statistically on HAM-D or BDI scores ( P = .67 ) ; adjustment for baseline levels of depression yielded an essentially identical result . Growth curve models revealed that all groups exhibited statistically and clinical ly significant reductions on HAM-D and BDI scores . However , patients receiving medication alone exhibited the fastest initial response ; among patients receiving combination therapy , those with less severe depressive symptoms initially showed a more rapid response than those with initially more severe depressive symptoms . CONCLUSIONS An exercise training program may be considered an alternative to antidepressants for treatment of depression in older persons . Although antidepressants may facilitate a more rapid initial therapeutic response than exercise , after 16 weeks of treatment exercise was equally effective in reducing depression among patients with MDD Purpose . Worsening of schizophrenia symptoms is related to stress and anxiety . People with schizophrenia often experience difficulties in coping with stress and possess a limited repertoire of coping strategies . A r and omised comparative trial was undertaken in patients with schizophrenia to evaluate changes in state anxiety , psychological stress and subjective well-being after single sessions of yoga and aerobic exercise compared with a control condition . Method . Forty participants performed a single 30-min yoga session , 20-min of aerobic exercise on a bicycle ergometre at self-selected intensity and a 20-min no exercise control condition in r and om order . Results . After single sessions of yoga and aerobic exercise individuals with schizophrenia or schizoaffective disorder showed significantly decreased state anxiety ( p < 0.0001 ) , decreased psychological stress ( p < 0.0001 ) and increased subjective well-being ( p < 0.0001 ) compared to a no exercise control condition . Effect sizes ranged from 0.82 for psychological stress after aerobic exercise to 1.01 for state anxiety after yoga . The magnitude of the changes did not differ significantly between yoga and aerobic exercise . Conclusion . People with schizophrenia and physiotherapists can choose either yoga or aerobic exercise in reducing acute stress and anxiety taking into account the personal preference of each individual The purpose of the present study was to examine the effects of exercise intensity on feeling states following two acute bouts of exercise ( i.e. , 50 % and 80 % of age-predicted maximal heart rate reserve : HRR ) in highly fit and unfit females . It was hypothesized that highly fit females would have increased positive well-being and /or reduced psychological distress post-exercise ( high intensity ) compared to unfit females while both groups would experience similar feeling states following moderate intensity exercise . Twelve highly fit and 12 unfit females completed 3 conditions : attention control and fitness test , and two acute bouts of exercise ( 30 minutes on a bicycle ergometer ) at 50 % and 80 % age-predicted HRR . Pre- and post-exercise feeling states were measured via the Subjective Experiences Exercise Scale ( McAuley & Courneya , 1994 ) . Analyses indicated a time x condition x fitness interaction F(2,21)=6.07 , p<.01 ( eta2 = .37 ) for psychological distress . Follow-up univariate analyses revealed no change in the 50 % or control conditions , however , psychological distress significantly increased for the unfit participants F(1,11)=4.68,p<.05 ( eta2 = .29 ) while there was no change for the highly fit participants F(1,11)=2.14,p>.05 ( eta2 = .16 ) in the 80 % intensity condition . No fitness differences emerged with respect to positive well-being or fatigue . Therefore , the present study 's results substantiate the need to consider fitness level in dose-response studies , particularly ones which examine negative feeling states PURPOSE This study was design ed to determine if a single bout of moderate-intensity aerobic exercise would improve mood and well-being in 40 ( 15 male , 25 female ) individuals who were receiving treatment for major depressive disorder ( MDD ) . METHODS All participants were r and omly assigned to exercise at 60 - 70 % of age-predicted maximal heart rate for 30 min or to a 30-min period of quiet rest . Participants completed both the Profile of Mood States ( POMS ) and Subjective Exercise Experiences Scale ( SEES ) as indicators of mood 5 min before , and 5 , 30 , and 60 min following their experimental condition . RESULTS Both groups reported similar reductions in measures of psychological distress , depression , confusion , fatigue , tension , and anger . Only the exercise group , however , reported a significant increase in positive well-being and vigor scores . CONCLUSION Although 30 min of either moderate-intensity treadmill exercise or quiet rest is sufficient to improve the mood and well-being of patients with MDD , exercise appears to have a greater effect on the positively valenced states measured This study investigated the hypothesis that the effects of acute aerobic exercise on feeling states may be influenced by the objective dose of activity , subjective responses during exercise , and preexisting levels of feeling states . College-age women ( N = 80 ) completed baseline measures and were then r and omly assigned to 1 of 4 conditions : attention control for 10 min , or exercise for 10 min , 25 min , or 40 min . Levels of exertion and affect were assessed during exercise , and posttesting occurred 20 min following activity . Exercise enhanced revitalization in comparison with the control condition ; however , this effect occurred only for participants scoring low to moderate on the pretest . In addition , in-task feeling states predicted postexercise revitalization even after we controlled for the treatment , the pretest , and the Pretest x Treatment interaction Objective The purpose of this study was to assess the status of 156 adult volunteers with major depressive disorder ( MDD ) 6 months after completion of a study in which they were r and omly assigned to a 4-month course of aerobic e-ercise , sertraline therapy , or a combination of e-ercise and sertraline . Methods The presence and severity of depression were assessed by clinical interview using the Diagnostic Interview Schedule and the Hamilton Rating Scale for Depression ( HRSD ) and by self-report using the Beck Depression Inventory . Assessment s were performed at baseline , after 4 months of treatment , and 6 months after treatment was concluded ( ie , after 10 months ) . Results After 4 months patients in all three groups e-hibited significant improvement ; the proportion of remitted participants ( ie , those who no longer met diagnostic criteria for MDD and had an HRSD score < 8) was comparable across the three treatment conditions . After 10 months , however , remitted subjects in the e-ercise group had significantly lower relapse rates ( p = .01 ) than subjects in the medication group . Exercising on one ’s own during the follow-up period was associated with a reduced probability of depression diagnosis at the end of that period ( odds ratio = 0.49 , p = .0009 ) . Conclusions Among individuals with MDD , e-ercise therapy is feasible and is associated with significant therapeutic benefit , especially if e-ercise is continued over time This study investigated : ( a ) whether moderate intensity aerobic exercise exerted a significant affective influence during , and postexercise , ( b ) the nature of the affective response to exercise in relation to positive and negative affects , and affects associated with physiological distress , and ( c ) whether exercise induced affect was significantly influenced by exercise behaviour . Habitual exercisers ( n = 15 ) and sedentary participants ( n = 13 ) undertook three r and omly allocated interventions ; ( a ) exercise ( EX ; i.e. , 20 min of cycling at 60 % estimated VO2max ) , ( b ) normal workstation duties for 60 min ( WRK ) , and ( c ) a 60 min sedentary lunch break ( SED ) . Affect was measured pre , post , and 90 min postintervention , as well as every 5 min during exercise , using the Subjective Exercise Experiences Scale ( SEES ; McAuley & Courneya , 1994 ) . Exercise behaviour had no significant affect on affective responses to exercise in this study ( p > .05 ) . Significant ( p < .05 ) postintervention increases in positive affect were found for EX compared to WRK and SED indicating that exercise did produce a positive affective influence . Despite enduring postexercise ( i.e. , 90 min ) improvements in both positive and negative affects , and affects related to fatigue , the affective response during exercise was characterised by significant ( p < .05 ) decreases in levels of positive affect and increased levels of affects related to fatigue BACKGROUND Depression in elderly people may be contributed to by the multiple losses of aging . Exercise has the potential to positively impact many of these losses simultaneously . We tested the hypothesis that progressive resistance training ( PRT ) would reduce depression while improving physiologic capacity , quality of life , morale , function and self-efficacy without adverse events in an older , significantly depressed population . METHODS We conducted a 10-week r and omized controlled trial of volunteers aged 60 and above with major or minor depression or dysthymia . Subjects were r and omized for 10 weeks to either a supervised PRT program three times a week or an attention-control group . RESULTS A total of 32 subjects aged 60 - 84 , mean age 71.3 + /- 1.2 yr , were r and omized and completed the study . No significant adverse events occurred . Median compliance was 95 % . PRT significantly reduced all depression measures ( Beck Depression Inventory in exercisers 21.3 + /- 1.8 to 9.8 + /- 2.4 versus controls 18.4 + /- 1.7 to 13.8 + /- 2 , p = .002 ; Hamilton Rating Scale of Depression in exercisers 12.3 + /- 0.9 to 5.3 + /- 1.3 versus controls 11.4 + /- 1.0 to 8.9 + /- 1.3 , p = .008 ) . Quality of life subscales of bodily pain ( p = .001 ) , vitality ( p = .002 ) , social functioning ( p = .008 ) , and role emotional ( p = .02 ) were all significantly improved by exercise compared to controls . Strength increased a mean of 33 % + /- 4 % in exercisers and decreased 2 % + /- 2 % in controls ( p < .0001 ) . In a multiple stepwise regression model , intensity of training was a significant independent predictor of decrease in depression scores ( r2 = .617 , p = .0002 ) . CONCLUSIONS PRT is an effective antidepressant in depressed elders , while also improving strength , morale , and quality of life This laboratory experiment used r and om digit dialing procedures to recruit a community sample of physically inactive participants into a study that was design ed to examine the impact of different intensities of acute aerobic exercise on feeling states . Sedentary men ( n Output:

The main findings of the review were that acute aerobic exercise improves positive well-being and have the potential to reduce psychological distress and could help reduce the risks of future CVD . However , due to the limited number of studies , it is still unclear which form of exercise yields superior psychological benefits .

MS214131

***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 aim of this study was to evaluate the feasibility of using a 2-stage implant system in a single-stage procedure and to study the impact of the microgap between the implant and the abutment . MATERIAL S AND METHODS Sixty edentulous patients ( Cawood class V or VI ) participated in this study . After r and omization , 20 patients received 2 IMZ implants placed in a single-stage procedure , 20 patients received 2 IMZ implants placed in the traditional 2-stage procedure , and 20 patients were treated with 2 ITI implants ( single-stage procedure ) . The implants were placed in the canine area of the m and ible . After 3 months , m and ibular overdentures were fabricated , supported by a bar- and -clip attachment . A st and ardized clinical and radiographic evaluation was performed immediately after prosthesis placement and after 12 and 24 months . RESULTS One IMZ implant of the 1-stage group and 1 IMZ implant of the 2-stage group were lost after 6 and 12 months , respectively . Apart from several significant but clinical ly irrelevant differences , the 3 groups did not appear to differ markedly with regard to clinical parameters during the evaluation period . The mean bone loss within the first 2 years of functioning ( 1.1 mm IMZ 1-stage , 0.8 mm IMZ 2-stage , 1.2 mm ITI ) was comparable for the 3 groups . DISCUSSION AND CONCLUSIONS The results of this study suggest that dental implants design ed for a submerged implantation procedure can also be used in a single-stage procedure and may be as predictable as when the same implants used in a 2-stage procedure or as 1-stage implants . Placement of the microgap at the crestal level in 2-stage implants did not appear to have an adverse effect on the amount of peri-implant bone loss at 2 years in this study population AIM The aim of this study was to compare the clinical outcome of submerged vs. non-submerged tapered implants placed into fresh extraction sockets . MATERIAL S AND METHODS A prospect i ve , controlled , multicenter , r and omized , clinical trial has been performed in two centers in Rome and Torino ( Italy ) . Thirty healthy patients were recruited according to the following inclusion criteria : need for an immediate post extraction implant , ages between 18 and 70 , horizontal defect depth < 2 mm , smokers < 10 cigarettes/day and absence of any circumstance or condition that could represent contraindications to implant surgery . The patients were r and omly allocated to submerged or non-submerged treatment groups immediately after flap elevation and tooth extraction . Submerged implants were exposed 8 weeks after the first surgery ; all implants were loaded with provisional restorations 12 weeks after the first surgery and with definitive restoration 12 weeks thereafter . Clinical and radiographic parameters were evaluated at baseline , at implant loading and at the 1-year follow-up visit . RESULTS The results showed statistically significant differences between the two groups in the mean value of keratinized tissue ( KT ) height after surgery that was significantly reduced for submerged implants when compared with transmucosal implants ( mean reduction of KT at year follow-up : T group 0.2 mm , S group 1.3 mm ; P=0.007 ) . CONCLUSION Similar outcomes were found for submerged and non-submerged implants placed in fresh extraction sockets with a horizontal peri-implant defect smaller than 2 mm , except for a reduction of KT in the submerged group . Either with a submerged or a non-submerged procedure , 1 mm of mean soft tissue recession is seen after 1 year when compared with the pre- extraction situation The osseointegration of endosseous dental implants is well documented . Implants have proven to be a viable treatment option for the replacement of missing teeth . The surgical phase of implant dentistry for most implant systems involves two stages — the placement of the implant and its subsequent uncovering . The IMZ ( Interpore International ) implant system is classically a two-stage system . No significant differences were demonstrated in osseointegration and soft tissue healing for IMZ implants placed in one-stage and two-stage procedures in this pilot study In the present multi-center study , non-submerged ITI implants were prospect ively followed to evaluate their long-term prognosis in fully and partially edentulous patients . In a total of 1003 patients , 2359 implants were consecutively inserted . Following a healing period of 3 - 6 months , the successfully integrated implants were restored with 393 removable and 758 fixed restorations . Subsequently , all consecutive implants were documented annually up to 8 years . At each examination , the clinical status of all implants was evaluated according to predefined criteria of success . Therefore , the data base allowed the evaluation of 8-year cumulative survival and success rates for 2359 implants . In addition , cumulative success rates were calculated for implant subgroups divided per implant type , implant length , and implant location . Furthermore , the actual 5-year survival and success rates could be determined for 488 implants . During the healing period , 13 implants did not successfully integrate , whereas 2346 implants fulfilled the predefined criteria of success . This corresponds with an early failure rate of 0.55 % . During follow-up , 19 implants were classified as failures due to several reasons . In addition , 17 implants ( approximately 0.8 % ) demonstrated at the last annual examination a suppurative periimplant infection . Including 127 drop out implants (= 5.4 % drop out rate ) into the calculation , the 8-year cumulative survival and success rates result ed in 96.7 % and 93.3 % , respectively . The analysis of implant subgroups showed slightly more favorable cumulative success rates for screw type implants ( > 95 % ) compared to hollow-cylinder implants ( 91.3 % ) , and clearly better success rates for m and ibular implants ( approximately 95 % ) when compared to maxillary implants ( approximately 87 % ) . The actual 5-year survival and success rates of 488 implants with 98.2 % and 97.3 % , respectively , were slightly better than the estimated 5-year cumulative survival and success rates of 2359 implants indicating that the applied life table analysis is a reliable statistical method to evaluate the long-term prognosis of dental implants . It can be concluded that non-submerged ITI implants maintain success rates well above 90 % in different clinical centers for observation periods up to 8 years BACKGROUND The use of a submerged implant system in a nonsubmerged surgical procedure has been reported to have promising results . At the time this study was initiated , no prospect i ve , comparative studies with r and omization between submerged and nonsubmerged surgical techniques had been published . PURPOSE To evaluate the submerged and nonsubmerged surgical techniques when treating m and ibular edentulism using a submerged implant system , with regard to implant survival and complications . MATERIAL S AND METHODS A total of 77 patients were included and treated at nine clinics in Sweden and Norway . In total , 404 Brånemark System implants ( st and ard and MkII implants ) were inserted in the edentulous m and ible ; 198 implants according to the nonsubmerged protocol and 206 implants according to the traditional submerged procedure . The follow-up period was up to 36 months after prosthesis insertion . RESULTS In the nonsubmerged group , 17 implants out of 198 implants ( 8.6 % ) were lost and in the submerged group , 5 out of 206 implants ( 2.4 % ) were lost . All implant failures occurred before the delivery of the final prosthesis . No major complications were reported during the implant surgery . However , at the clinical check-up postoperatively and at the abutment connection surgery , 6 patients in the nonsubmerged group complained of pain at the implant sites , whereas there were no complaints of pain in the submerged group . CONCLUSIONS The results of this study suggest that a turned Brånemark implant design ed for a submerged implant placement procedure can be used in a nonsubmerged procedure and may be as predictable as the conventional submerged approach The aim of this prospect i ve study was to compare the clinical integration and survival of Brånemark fixtures when using the conventional 2-stage surgical procedure to 1-stage surgical approach in completely and partially edentulous m and ibles . A total of 85 patients were consecutively treated for partial ( n = 35 ) or complete ( n = 50 ) m and ibular edentulousness . Fixtures removed because of mobility , pain or infection were counted as failures . The first 10 patients of each group were selected for radiographical analysis of crestal bone changes 1 year after prosthesis insertion . In 33 patients with edentulous m and ibles , 170 fixtures were placed in a 1-stage approach . In this group , 4 fixtures ( 2.4 % ) were lost prior to prosthetic restoration . Seventeen edentulous patients received a total of 70 fixtures in a 2-stage procedure . Out of these , 5 fixtures ( 7.1 % ) were lost at abutment connection . In 17 partially edentulous patients , 41 fixtures were inserted in a 1-stage approach . Two fixtures ( 5 % ) were lost in this group . Finally , 18 partially edentulous patients received a total of 49 fixtures in a 2-stage procedure . Out of these , 6 fixtures ( 12 % ) were lost at abutment connection . In total 313 of the 330 installed m and ibular implants were loaded between 6 and 12 months ( 94.8 % success ) . No further losses occurred in the implants functioning at least 1 year ( 267 implants ) or at least 2 years ( 59 implants ) . Statistical analysis ( Chi square test ) revealed no difference in fixture survival between the treatment modalities . Radiographical analysis after 1 year of functional loading showed the typical bone resorption changes up to the most coronal implant thread in both modalities . Although this study pertains to relatively early loading of 2 years , the results seem to indicate that in the m and ible a 1-stage surgical approach with Brånemark fixtures may be as predictable as the conventional 2-stage procedure OBJECTIVE To evaluate bone-level alterations that occurred at implants of the Astra Tech(R ) System that were placed in the load carrying , posterior parts of the dentition using either a submerged ( two-stage ) or a non-submerged ( one-stage ) installation protocol . MATERIAL AND METHODS Eighty-four patients that required 115 fixed partial dentures ( FPDs or cases ) entered the prospect i ve study . All subjects were assigned one patient and > or = one case numbers . For the r and omization of cases , a custom-made program based on balanced r and om permuted blocks was utilized . The cases were assigned to two treatment groups , namely one-stage installation procedure , non-submerged technique ( group A ) and two-stage installation procedure , submerged technique ( group B ) . Several subjects contributed with cases to both groups A and B. Periodontal , endodontal and open caries lesions were treated prior to implant installation . All patients received careful oral hygiene instruction and training in self-performed plaque control measures . The surgical technique used for fixture installation followed the outline described in the manual for the Astra Tech System . The FPDs were placed 3 months ( m and ible ) and 6 months ( maxilla ) following implant installation . Immediately following FPD placement , a baseline examination was performed that included assessment of plaque , soft-tissue inflammation and bone level . Clinicians who were otherwise not involved in the study performed the radiographic measurements . Clinical and radiographical examinations were repeated once a year after the baseline examination . DATA ANALYSIS The primary outcome variable was the change in the bone level at the implants from the time of placement of the bridge ( FPD ) to the 1- and 2-year reexaminations . Fisher 's permutation test was used to test if differences existed between groups A and B , and between patients ( men/women , smokers/non-smokers , age ) , sites ( maxilla/m and ible ) and implants ( length , diameter ) . Pitman 's test was used to study correlations between bone shape and quality data and different radiographic bone-level data . RESULTS It was demonstrated that tissue healing following implant installation appeared to be independent of the surgical protocol , i.e. whether the marginal portions of the implants during surgery were fully or only partly submerged under the ridge mucosa . Thus , ( i ) in both treatment groups the number of implants that failed to osseointegrate ( early failures ) was small ( < 2 % ) ; ( ii ) at the end of the recommended periods of bone healing prior to loading , - in both groups , maxilla=6 months and m and ible=3 months - the level of the marginal bone was close to the coronal rim of the fixture ; group A : 1.54+/-0.92 mm , group B : 1.31+/-0.77 mm . The current study also demonstrated that irrespective of surgical protocol ( two-stage , one-stage ) , implants supporting the FPDs exhibited only small amount of radiographic bone loss during the first year of function ( group A : 0.02+/-038 mm , group B : 0.17+/-0.64 mm ) . Moreover , during the second year of function , the amount of additional bone loss that occurred in the two treatment groups was close to zero . CONCLUSION Periimplant bone-level change during function seemed to be unrelated to whether initial soft- and hard-tissue healing following implant installation had occurred under submerged or non-submerged conditions OBJECTIVE The aim of this study was to evaluate the Output:

On a patient , rather than per implant basis , the meta-analyses showed no statistically significant differences for prosthesis and implant failures , though trends , especially in fully edentulous patients , favoured 2-stage ( submerged ) implants . The 1-stage approach might be preferable in partially edentulous patients since it avoids one surgical intervention and shortens treatment times , while a 2-stage submerged approach could be indicated when an implant has not obtained an optimal primary stability or when barriers are used for guided tissue regeneration , or when it is expected that removable temporary prostheses could transmit excessive forces on the penetrating abutments especially in fully edentulous patients

MS214132

***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: Stroke patients usually suffer from asymmetric posture due to hemi-paresis that can result in reduced postural controllability leading to a balance deficit . This deficit increases the risk of falls , which often makes them dependent on caregivers for community ambulation , thus deteriorating their quality of life . Conventional balance training involves rehabilitation exercises performed under physiotherapist ’s supervision , where the scarcity of trained professionals as well as the cost of clinic-based rehabilitation programs can deter stroke survivors from undergoing regular balance training . Thus , research ers have been exploring technology-assisted solutions , e.g. , home-based virtual reality ( VR ) setup . In this paper , we developed a VR-based balance training ( VBaT ) platform , where VR-augmented user-interface using Nintendo Wii balance boardwas tested in a laboratory setting for its feasibility . The VBaT offered tasks of varying difficulties to the participants that adapted to individual performance capability during balance training . We performed a preliminaryusability study with 7 stroke survivors ( post-stroke period > 6 months ) . Preliminary results indicate the potential of theVBaT system to cause improvement in overall average task performance over the course of training while using the VBaT. Thus the VBaT system is proposed to be a step toward an effective balance training platform for people with balance disorder Abstract Objective : To contrast changes in clinical and kinematic measures of upper extremity movement in response to virtually simulated and traditionally presented rehabilitation interventions in persons with upper extremity hemiparesis due to chronic stroke . Design : Non-r and omized controlled trial . Setting : Ambulatory research facility . Participants : Subjects were a volunteer sample of twenty one community-dwelling adults ( mean age : 51 ± 12 years ) with residual hemiparesis due to stroke more than 6 months before enrollment ( mean : 74 ± 48 months ) , recruited at support groups . Partial range , against gravity shoulder movement and at least 10 ° of active finger extension were required for inclusion . All subjects completed the study without adverse events . Interventions : A 2 weeks , 24-hour program of robotic/virtually simulated , arm and finger rehabilitation activities was compared to the same dose of traditionally presented arm and finger activities . Results : Subjects in both groups demonstrated statistically significant improvements in the ability to interact with real-world objects as measured by the Wolf Motor Function Test ( P = 0.01 ) . The robotic/virtually simulated activity ( VR ) group but not the traditional , repetitive task practice ( RTP ) group demonstrated significant improvements in peak reaching velocity ( P = 0.03 ) and finger extension excursion ( P = 0.03 ) . Both groups also demonstrated similar improvements in kinematic measures of reaching and grasping performance such as increased shoulder and elbow excursion along with decreased trunk excursion . Conclusions : Kinematic measurements identified differing adaptations to training that clinical measurements did not . These adaptations were targeted in the design of four of the six simulations performed by the simulated activity group . Finer grained measures may be necessary to accurately depict the relative benefits of dose matched motor interventions Abstract Purpose state : The aim of this preliminary study was to test a data glove , CyberTouch ™ , combined with a virtual reality ( VR ) environment , for using in therapeutic training of reaching movements after spinal cord injury ( SCI ) . Method : Nine patients with thoracic SCI were selected to perform a pilot study by comparing two treatments : patients in the intervention group ( IG ) conducted a VR training based on the use of a data glove , CyberTouch ™ for 2 weeks , while patients in the control group ( CG ) only underwent the traditional rehabilitation . Furthermore , two functional parameters were implemented in order to assess patient ’s performance of the sessions : normalized trajectory lengths and repeatability . Results : Although no statistical significance was found , the data glove group seemed to obtain clinical changes in the muscle balance ( MB ) and functional parameters , and in the dexterity , coordination and fine grip tests . Moreover , every patient showed variations in at least one of the functional parameters , either along Y-axis trajectory or Z-axis trajectory . Conclusions : This study might be a step forward for the investigation of new uses of motion capture systems in neurorehabilitation , making it possible to train activities of daily living ( ADLs ) in motivational environments while measuring objective ly the patient ’s functional evolution . Implication s for Rehabilitation Key findings : A motion capture application based on a data glove is presented , for being used as a virtual reality tool for rehabilitation . This application has provided objective data about patient ’s functional performance . What the study has added : ( 1 ) This study allows to open new areas of research based on the use of different motion capture systems as rehabilitation tools , making it possible to train Activities of Daily Living in motivational environments . ( 2 ) Furthermore , this study could be a contribution for the development of clinical protocol s to identify which types of patients will benefit most from the VR treatments , which interfaces are more suitable to be used in neurorehabilitation , and what types of virtual exercises will work best Background Many studies have demonstrated the usefulness of repetitive task practice by using robotic-assisted gait training ( RAGT ) devices , including Lokomat , for the treatment of lower limb paresis . Virtual reality ( VR ) has proved to be a valuable tool to improve neurorehabilitation training . The aim of our pilot r and omized clinical trial was to underst and the neurophysiological basis of motor function recovery induced by the association between RAGT ( by using Lokomat device ) and VR ( an animated avatar in a 2D VR ) by study ing electroencephalographic ( EEG ) oscillations . Methods Twenty-four patients suffering from a first unilateral ischemic stroke in the chronic phase were r and omized into two groups . One group performed 40 sessions of Lokomat with VR ( RAGT + VR ) , whereas the other group underwent Lokomat without VR ( RAGT-VR ) . The outcomes ( clinical , kinematic , and EEG ) were measured before and after the robotic intervention . Results As compared to the RAGT-VR group , all the patients of the RAGT + VR group improved in the Rivermead Mobility Index and Tinetti Performance Oriented Mobility Assessment . Moreover , they showed stronger event-related spectral perturbations in the high-γ and β b and s and larger fronto- central cortical activations in the affected hemisphere . Conclusions The robotic-based rehabilitation combined with VR in patients with chronic hemiparesis induced an improvement in gait and balance . EEG data suggest that the use of VR may entrain several brain areas ( probably encompassing the mirror neuron system ) involved in motor planning and learning , thus leading to an enhanced motor performance . Trial registration Retrospectively registered in Clinical Trials on 21 - 11 - 2016 , n . NCT02971371 Abstract Purpose : To describe the novel BrightArm Duo bimanual upper extremity ( UE ) rehabilitation system ; to determine its technology acceptance and clinical benefit for older hemiplegic participants . Methods : The system table tilted to adjust arm gravity loading . Participants wore arm supports that sensed grasp strength and wrist position on the table . Wrist weights further increased shoulder exertion . Games were design ed to improve UE strength , motor function , cognition and emotive state and adapted automatically to each participant . The system underwent feasibility trials spanning 8 weeks in two skilled nursing facilities ( SNFs ) . Participants were evaluated pre-therapy and post-therapy using st and ardized clinical measures . Computerized measures of supported arm reach , table tilt and number of arm repetitions were stored on a remote server . Outcomes : Seven participants had significant improvements in their active range of shoulder movement , supported arm reach , shoulder strength , grasp strength and their ability to focus . The group demonstrated higher arm function measured with FMA ( p = 0.01 ) and CAHAI ( p = 0.05 ) , and had an improvement in depression ( Becks Depression Inventory , II ) . BrightArm Duo technology was well accepted by participants with a rating of 4.4 out of 5 points . Conclusions : Given these findings , it will be beneficial to evaluate the BrightArm Duo application in SNF maintenance programs . Implication s for Rehabilitation Integrative rehabilitation that addresses both physical and cognitive domains is promising for post-stroke maintenance in skilled nursing facilities . Simultaneous bilateral arm exercise may improve arm function in older hemiplegic patients several years after stroke . Virtual reality games that adapt to the patient can increase attention and working memory while decreasing depression in elderly Background Down syndrome ( DS ) has unique physical , motor and cognitive characteristics . Despite cognitive and motor difficulties , there is a possibility of intervention based on the knowledge of motor learning . However , it is important to study the motor learning process in individuals with DS during a virtual reality task to justify the use of virtual reality to organize intervention programs . The aim of this study was to analyze the motor learning process in individuals with DS during a virtual reality task . Methods A total of 40 individuals participated in this study , 20 of whom had DS ( 24 males and 8 females , mean age of 19 years , ranging between 14 and 30 yrs . ) and 20 typically developing individuals ( TD ) who were matched by age and gender to the individuals with DS . To examine this issue , we used software that uses 3D images and reproduced a coincidence-timing task . Results The results showed that all individuals improved performance in the virtual task , but the individuals with DS that started the task with worse performance showed higher difference from the beginning . Besides that , they were able to retain and transfer the performance with increase of speed of the task . Conclusion Individuals with DS are able to learn movements from virtual tasks , even though the movement time was higher compared to the TD individuals . The results showed that individuals with DS who started with low performance improved coincidence- timing task with virtual objects , but were less accurate than typically developing individuals . Trial registration Clinical Trials.gov Identifier : NCT02719600 Background Dexterous manipulation of the h and , one of the features of human motor control , is often compromised after stroke , to the detriment of basic functions . Despite the importance of independent movement of the digits to activities of daily living , relatively few studies have assessed the impact of specifically targeting individuated movements of the digits on h and rehabilitation . The purpose of this study was to investigate the impact of such finger individuation training , by means of a novel mechatronic-virtual reality system , on fine motor control after stroke . Methods An actuated virtual keypad ( AVK ) system was developed in which the impaired h and controls a virtual h and playing a set of keys . Creation of individuated digit movements is assisted by a pneumatically actuated glove , the PneuGlove . A study examining efficacy of the AVK system was subsequently performed . Participants had chronic , moderate h and impairment result ing from a single stroke incurred at least 6 months prior . Each subject underwent 18 hour-long sessions of extensive therapy ( 3x per week for 6 weeks ) targeted at finger individuation . Subjects were r and omly divided into two groups : the first group ( Keypad : N = 7 ) utilized the AVK system while the other group ( OT : N = 7 ) received a similarly intensive dose of occupational therapy ; both groups worked directly with a licensed occupational therapist . Outcome measures such as the Jebsen-Taylor H and Function Test ( JTHFT ) , Action research Arm Test ( ARAT ) , Fugl-Meyer Upper Extremity Motor Assessment /H and subcomponent ( FMUE/FMH ) , grip and pinch strengths were collected at baseline , post-treatment and one-month post-treatment . Results While both groups exhibited some signs of change after the training sessions , only the Keypad group displayed statistically significant improvement both for measures of impairment ( FMH : p = 0.048 ) and measures of task performance ( JTHFT : p = 0.021 ) . Additionally , the finger individuation index – a measure of finger independence – improved only for the Keypad group after training ( p = 0.05 ) in the subset ( Keypad : N = 4 ; OT : N = 5 ) of these participants for which it was measured . Conclusions Actively assisted individuation therapy comprised of non task-specific modalities , such as can be achieved with virtual platforms like the AVK described here , may prove to be valuable clinical tools for increasing the effectiveness and efficiency of therapy following stroke Immersive virtual reality ( IVR ) offers new possibilities to perform treatments in an ecological and interactive environment with multimodal online feedbacks . Sixteen school-aged children ( mean age 11 ± 2.4 years ) with Bilateral CP — diplegia , attending mainstream schools were recruited for a pilot study in a pre – post treatment experimental design . The intervention was focused on walking competences and endurance and performed by the Gait Real-time Analysis Interactive Lab ( GRAIL ) , an innovative treadmill platform based on IVR . The participants underwent eighteen therapy sessions in 4 weeks . Functional evaluations , instrumental measures including GAIT analysis and parental question naire were utilized to assess the treatment effects . Walking pattern ( stride length left and right side , respectively p = 0.001 and 0.003 ; walking speed p = 0.001 ) , endurance ( 6MWT , p = 0.026 ) , gross motor abilities ( GMFM-88 , p = 0.041 ) and most kinematic and kinetic parameters significantly improved after the intervention . The changes were mainly predicted by age and cognitive abilities . The effect could have been due to the possibility of IVR to foster integration of motor/perceptual competences beyond the training of the walking ability , giving a chance of improvement also to older and already treated children The video game-based therapy emerged as a potential valid tool in improving balance in several neurological conditions with controversial results , whereas little information is available regarding the use of this therapy in subacute stroke patients . The aim of this study was to investigate the efficacy of balance training using video game-based intervention on functional balance and disability in individuals with hemiparesis due to stroke in subacute phase . Fifty adult stroke patients participated to the study : 25 subjects were r and omly assigned to balance training with Wii Fit , and the other 25 subjects were assigned to usual balance therapy . Both groups were also treated with conventional physical therapy ( 4 Output:

Results : We summarize the literature which highlights that a range of effective VR approaches are available . A range of benefits were associated with VR interventions , including improvement in motor functions , greater community participation , and improved psychological and cognitive function . Conclusions : The results from this review provide support for the use of VR as part of a neurorehabilitation program in maximizing recovery

MS214133

***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 and hypothesisThe purpose of the study was to evaluate and compare the clinical values of tension-free vaginal tape ( TVT ) , tension-free vaginal tape-transobturator ( TVT-O ) , or tension-free vaginal tape-Secur ( TVT-Secur ) as treatment for female stress urinary incontinence . Methods The pre-operative and 1-year post-operative follow-up protocol s for patients who were treated with serial mid-urethral tension-free tape procedures in two hospitals from October 2008 to December 2009 were prospect ively studied . These patients were r and omly allocated to TVT , TVT-O , or TVT-Secur . Results A total of 102 women participated . At the 1-year follow-up , complications were not statistically different across the three groups except for pain in the thigh , which was more common in the TVT-O group . The overall efficacy and cure rate were similar between the TVT and TVT-O groups , but were significantly lower in the TVT-Secur group . Conclusions A comparison of the three procedures shows that TVT-O is easy to operate and is as safe as TVT-Secur , and it has similar long-term efficacy to TVT , though , as one of the third-generation mid-urethral tension-free tapes , TVT-Secur is still being evaluated . Basing on the outcome of our study , it had rare complications but unsatisfactory efficacy , and we suggest that TVT-Secur is not fit for severe cases . However , observation and comparison of these groups in a larger sample size on a longer term are needed Objective To compare the outcomes of tension- free vaginal tape ( TVT ) and transobturator tape ( TOT ) in the treatment of female stress urinary incontinence with or without concomitant pelvic organ prolapse ( POP ) . Methods One hundred and forty patients with SUI were r and omly allocated to TVT ( n = 70 ) or TOT ( n = 70 ) . The objective outcomes were assessed with a stress test , 1-h pad test . Subjective outcomes were assessed with UDI-6/(IIQ-7 ) question naires . Results The surgical outcomes revealed no significant difference between TVT and TOT surgical route . Both the subjective and objective cure rates were 91.4 % in the TOT group , while 90 and 92.8 % in the TVT group , respectively . The results showed the association to pelvic floor surgical techniques did not diminish a year later . TOT procedure has a shorter operative time for patients without concomitant surgery . Conclusion The efficacy and safety of TVT procedure were similar to that of TOT procedure for female stress urinary incontinence with or without concomitant POP The aim of this r and omized clinical trial was to compare the cure rate and the rate of complications of the tension-free vaginal tape ( TVT ) with those of the tension free vaginal tape obturator ( TVT-O ) procedure after one year of follow-up . The study was powered to show a ten per cent difference in cure rate and /or rate of complications . Of the initially treated 267 women 134 in the TVT group and 131 in the TVT-O group were evaluated . A cough stress test and a 24 h pad test were used as objective outcome measures . Subjective outcome was assessed by different condition-specific quality of life question naires and general health by the EQ-5D question naire . Objective cure rate was 95.5 % in the TVT patients and 93.1 % in TVT-O patients . Subjective cure rates showed significant improvement at one the year follow up in both groups . No significant differences in cure rates between groups were seen . The complication rate was equal in both groups Purpose To evaluate in a comprehensive way TVT in comparison with TOT , the results of a single-center RCT are presented . Many studies addressed efficacy and safety of TVT and TOT . Methods Women included were adults having predominant SUI with positive stress test . They were r and omized to get either TVT ( Gynecare ® ) or TOT ( Aris ® ) . All women were seen 1 week , 3 , 6 , 12 , 18 , and 24 months . Results Seventy-one women completed 2-year follow-up . Median age was 47 ( range 33–60 years ) . Mean ± SD BMI in TVT group was 34 ± 5 while in TOT group was 32 ± 5 kg/m2 . POP of any degree was seen in 50 % ( 35 women ) . At 1 year , pad test – negative women were 31 and 29 for TVT and TOT , respectively . At 2 years , figures became 28 in TVT group and 27 in TOT . At 1 year , UDI 6 and IIQ 7 decreased by 78.5 and 81 % for TVT and by 69 % and 75 % for TOT group . At 2 year , comparable percentages were 73 and 79 % for TVT and 69 and 82 % for TOT . Fifteen unique patients had adverse events , 10 of them had TOT . Conclusions Both tapes have similar efficacy , regarding cure of incontinence . TVT is more effective , albeit insignificantly , than TOT at 2 years . However , serious adverse events were more frequent with TVT , yet TOT has more unique adverse events BACKGROUND Contemporary surgical treatment of female stress urinary incontinence ( SUI ) includes retropubic and transobturator ( TO ) midurethral slings ( MUS ) . Case series of single-incision slings ( SIS ) have shown similar outcomes with lower morbidity . OBJECTIVE Our aim was to assess the cure rates , complications , and quality -of-life impact of one st and ard TO MUS and two SIS . DESIGN , SETTING , AND PARTICIPANTS Ninety consecutive patients with clinical ly and urodynamically proven SUI were enrolled in an exploratory r and omised phase 2 trial . Patients with previous SUI surgery , major pelvic organ prolapse , mixed incontinence , or detrusor overactivity were excluded . INTERVENTIONS Patients were treated r and omly with TVT-O , TVT-Secur , or Mini-Arc . MEASUREMENTS Postoperative visits were scheduled at 6 and 12 mo . The King 's Health Question naire ( KHQ ) was repeated at 6 mo . Cure was defined as the absence of urine leakage , no pad use , and a negative cough test at 12 mo . Pain and other complications were also investigated . RESULTS AND LIMITATIONS Cure rate was 83 % after TVT-O , 67 % after TVT-Secur , and 87 % after Mini-Arc . Improvement was found in 10 % , 13 % , and 7 % of the patients , respectively . Failures were 7 % after TVT-O and Mini-Arc and 20 % after TVT-Secur . TVT-O and Mini-Arc improved at least 15 points in > 80 % of the patients in six KHQ domains , whereas TVT-Secur could only achieve improvement in three of the nine domains . The pain score was lower in the Mini-Arc group . Complications were more numerous after TVT-O. This study has the limitations inherent in a phase 2 trial with a follow-up limited to 12 mo . CONCLUSIONS Mini-Arc offers cure and improvement rates similar to TVT-O , whereas TVT-Secur may yield an inferior outcome . These findings recommend the urgent launch of large r and omised phase 3 studies comparing conventional MUS with SIS , with Mini-Arc the advised option Introduction and hypothesisA study was conducted to compare the efficacy and complications of TVT and TVT-O. Methods This study is a prospect i ve r and omized trial involving 300 women with primary SUI ; 149 received TVT , and 151 patients were treated with TVT-O. At the 1 year follow-up , 141 TVT patients and 147 TVT-O patients ( dropout , 5.3 % and 2.6 % ) were evaluated using urodynamic studies , vali date d question naires , and a 1-h pad test . Results The mean operating time was shorter in the TVT-O group ( p < 0.001 ) . Urinary retention was not significantly different ( p > 0.05 ) . Inner thigh discomfort was reported by 5.4 % of TVT-O patients . In the TVT and the TVT-O groups , respectively , 90.1 % and 88.4 % women were objective ly cured . The satisfaction with the surgical outcome reflects the significant decrease in the question naire mean symptom scores in both groups . Postoperative de novo urgency was significantly more common in the TVT-O patients ( p = 0.015 ) . Conclusion The groups showed comparable objective and subjective cure rates OBJECTIVES This prospect i ve , multicentre , r and omised study compared the safety and success rate of tension-free vaginal tape ( TVT ) and transobturator tape ( TOT ) in treatment of female stress urinary incontinence . METHODS Of 148 women , 73 were r and omised to TVT and 75 to TOT . Preoperative workups included case history , clinical examination , Urogenital Distress Inventory and Impact Incontinence Quality of life question naires , 1-h pad test , pelvic ultrasound , and urodynamics . Intra- and postoperative complications were the primary end point ; subjective and objective changes in SUI , and postoperative voiding dysfunctions were secondary end points . Patients were classified into two main categories : dry ( no leakage during clinical and /or stress test and /or reported by patients ) versus wet . Patients who referred being wet were separated into " improved " or " failure " on subjective analysis . Other outcome variables were quality of life question naires and VAS scale . Clinical checkups were conducted at 3 , 6 , 12 mo , and then annually . RESULTS Both techniques are safe and no significant differences emerged in intra- and postoperative complications . At a mean follow-up of 31 mo , the overall objective cure ( dry ) was 71.4 % for TVT and 77.3 % for TOT ( p = ns ) . When one considered " dry " plus " wet but improved , " these values increased to 90 % and 90.6 % , respectively ( p = ns ) . Median satisfaction rate was 9 ( range : 1 - 10 ) for both procedures . Postoperative storage symptoms are a controversial issue ; they persisted in 44 % of patients in TVT group versus 24 % in TOT group ( p<0.053 ) . CONCLUSIONS TOT appears as safe and effective as TVT in surgery for female SUI , with minimal complications at mean follow-up of 31 mo The aim of the study was to compare the efficacy and complications of the Transobturator tape ( Monarc ) vs the tension-free vaginal tape obturator ( TVT-O ) in women with urodynamic stress incontinence . A prospect i ve , r and omized study was conducted . One-hundred and twenty patients were included in the study , and 114 of them were available at 12 months follow-up . Sixty-one patients were subjected to the TVT-O procedure and 53 to the Monarc procedure . Subjective and objective cure and improvement rate and complications incidence were assessed . The objective cure rate was 87 % for the TVT-O procedure and 90 % for the Monarc group . The subjective cure rate was 80 % for the TVT-O group and 77 % for the Monarc group . The improvement was 13 and 11.5 % for the TVT-O and Monarc groups , respectively . There was one accidental injury to the urethra with the Monarc technique . The Monarc technique presents success rates and complications comparable to the TVT-O method at 1 year follow-up Introduction and hypothesisThe purpose of this study is to compare the retropubic tension-free vaginal tape ( TVT ) procedure with the inside-out transobturator approach ( TVT-O ) . Methods Multicenter r and omized controlled trial . One hundred forty-nine patients were r and omly allocated to either TVT ( n = 75 ) or TVT-O ( n = 74 ) . Interview , medical examination , pain scores , success rates , and quality of life assessment were recorded pre-operatively , and 2 , 6 , 12 , and 24 months post-operatively . Results One hundred forty-nine patients underwent surgery , and 132 completed a 24-month follow-up . Bladder injury rate was 5 % ( 4/75 ) in the TVT group and 2 % ( 2/74 ) in the TVT-O group ( p = 0.68 ) . There was no significant difference between the two groups , concerning overall cure rate and the patients ' satisfaction rate at 24 months follow-up . The range of mean pain scores was significantly higher after the TVT-O procedure post-operatively but not at 24 months follow-up . Conclusion TVT and TVT-O procedures both have an outcome associated with an increase in quality of life with no significant differences in satisfaction rates at 2 years follow-up BACKGROUND Midurethral slings have become the most preferred surgical treatment for female urinary incontinence . OBJECTIVE To compare the efficacy and safety of two midurethral sling procedures with a different technique of sling insertion 5 yr after intervention . DESIGN , SETTING , AND PARTICIPANTS Multicenter r and omized clinical trial conducted in seven public hospitals in Finl and including primary cases of stress urinary incontinence . INTERVENTION Surgical treatment with the retropubic tension-free vaginal tape ( TVT ) procedure or the transobturator tension-free vaginal tape ( TVT-O ) procedure . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Objective treatment success criteria were a negative stress test , a negative 24-h pad test , Output:

Conclusion TOT may have more valid effects than TVT in operative time and hospital stay . Besides , TOT method showed fewer complications and blood loss than TVT , but there was no significant difference between them . The scores of VAS , incontinence impact question naire short form-7 ( IIQ-7 ) , and urogenital distress inventory short form-6 ( UDI-6 ) were higher in TOT than TVT , but still no significant difference was observed .

MS214134

***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 Background Emergence of artemisinin-resistant malaria in Southeast Asian countries threatens the global control of malaria . Although K13 kelch propeller has been assessed for artemisinin resistance molecular marker , most of the mutations need to be vali date d. In this study , artemisinin resistance was assessed by clinical and molecular analysis , including k13 and recently reported markers , pfarps10 , pffd and pfmdr2 . Methods A prospect i ve cohort study in 1160 uncomplicated falciparum patients was conducted after treatment with artemisinin-based combination therapy ( ACT ) , in 6 sentinel sites in Myanmar from 2009 to 2013 . Therapeutic efficacy of ACT was assessed by longitudinal follow ups . Molecular markers analysis was done on all available day 0 sample s. Results True recrudescence treatment failures cases and day 3 parasite positivity were detected at only the southern Myanmar sites . Day 3 positive and k13 mutants with higher prevalence of underlying genetic foci predisposing to become k13 mutant were detected only in southern Myanmar since 2009 and comparatively fewer mutations of pfarps10 , pffd , and pfmdr2 were observed in western Myanmar . K13 mutations , V127 M of pfarps10 , D193Y of pffd , and T448I of pfmdr2 were significantly associated with day 3 positivity ( OR : 6.48 , 3.88 , 2.88 , and 2.52 , respectively ) . Conclusions Apart from k13 , pfarps10 , pffd and pfmdr2 are also useful for molecular surveillance of artemisinin resistance especially where k13 mutation has not been reported . Appropriate action to eliminate the resistant parasites and surveillance on artemisinin resistance should be strengthened in Myanmar . Trial registration This study was registered with Clinical Trials.gov , identifier NCT02792816 Background Artemisinin-based combination therapy has been first-line treatment for falciparum malaria in Myanmar since 2005 . The wide extent of artemisinin resistance in the Greater Mekong sub-region and the presence of mefloquine resistance at the Myanmar-Thail and border raise concerns over resistance patterns in Myanmar . The availability of molecular markers for resistance to both drugs enables assessment even in remote malaria-endemic areas . Methods A total of 250 dried blood spot sample s collected from patients with Plasmodium falciparum malarial infection in five malaria-endemic areas across Myanmar were analysed for kelch 13 sequence ( k13 ) and pfmdr1 copy number variation . K13 mutations in the region corresponding to amino acids 210–726 ( including the propeller region of the protein ) were detected by nested PCR amplification and sequencing , and pfmdr1 copy number variation by real-time PCR . In two sites , a sub-set of patients were prospect ively followed up for assessment of day-3 parasite clearance rates after a st and ard course of artemether-lumefantrine . Results K13 mutations and pfmdr1 amplification were successfully analysed in 206 and 218 sample s , respectively . Sixty-nine isolates ( 33.5 % ) had mutations within the k13 propeller region with 53 of these ( 76.8 % ) having mutations already known to be associated with artemisinin resistance . F446I ( 32 isolates ) and P574L ( 15 isolates ) were the most common examples . K13 mutation was less common in sites in western border regions ( 29 of 155 isolates ) compared to sample s from the east and north ( 40 of 51 isolates ; p < 0.0001 ) . The overall proportion of parasites with multiple pfmdr1 copies ( greater than 1.5 ) was 5.5 % . Seven sample s showed both k13 mutation and multiple copies of pfmdr1 . Only one of 36 patients followed up after artemether-lumefantrine treatment still had parasites at day 3 ; molecular analysis indicated wild-type k13 and single copy pfmdr1 . Conclusion The proportion of P. falciparum isolates with mutations in the propeller region of k13 indicates that artemisinin resistance extends across much of Myanmar . There is a low prevalence of parasites with multiple pfmdr1 copies across the country . The efficacy of artemisinin-based combination therapy containing mefloquine and lumefantrine is , therefore , expected to be high , although regular monitoring of efficacy will be important Background Intensified efforts are urgently needed to contain and eliminate artemisinin-resistant Plasmodium falciparum in the Greater Mekong subregion . Médecins Sans Frontières plans to support the Ministry of Health in eliminating P. falciparum in an area with artemisinin resistance in the north-east of Cambodia . As a first step , the prevalence of Plasmodium spp . and the presence of mutations associated with artemisinin resistance were evaluated in two districts of Preah Vihear Province . Methods A cross-sectional population -based study using a two-stage cluster sampling was conducted in the rural districts of Chhaeb and Chey Saen , from September to October 2013 . In each district , 30 clusters of 10 households were r and omly selected . In total , blood sample s were collected for 1,275 participants in Chhaeb and 1,224 in Chey Saen . Prevalence of Plasmodium spp . was assessed by PCR on dried blood spots . Plasmodium falciparum positive sample s were screened for mutations in the K13-propeller domain gene ( PF3D7_1343700 ) . Result The prevalence of Plasmodium spp . was estimated at 1.49 % ( 95 % CI 0.71–3.11 % ) in Chhaeb and 2.61 % ( 95 % CI 1.45–4.66 % ) in Chey Saen . Twenty-seven sample s were positive for P. falciparum , giving a prevalence of 0.16 % ( 95 % CI 0.04–0.65 ) in Chhaeb and 2.04 % ( 95 % CI 1.04–3.99 % ) in Chey Saen . Only 4.0 % of the participants testing positive presented with fever or history of fever . K13-propeller domain mutant type alleles ( C580Y and Y493H ) were found , only in Chey Saen district , in seven out of 11 P. falciparum positive sample s with enough genetic material to allow testing . Conclusion The overall prevalence of P. falciparum was low in both districts but parasites presenting mutations in the K13-propeller domain gene , strongly associated with artemisinin-resistance , are circulating in Chey Saen . The prevalence might be underestimated because of the absentees – mainly forest workers - and the workers of private companies who were not included in the study . These results confirm the need to urgently develop and implement targeted interventions to contain and eliminate P. falciparum malaria in this district before it spreads to other areas BACKGROUND Artemisinin-based combination therapies are the recommended first-line treatments of falciparum malaria in all countries with endemic disease . There are recent concerns that the efficacy of such therapies has declined on the Thai-Cambodian border , historically a site of emerging antimalarial-drug resistance . METHODS In two open-label , r and omized trials , we compared the efficacies of two treatments for uncomplicated falciparum malaria in Pailin , western Cambodia , and Wang Pha , northwestern Thail and : oral artesunate given at a dose of 2 mg per kilogram of body weight per day , for 7 days , and artesunate given at a dose of 4 mg per kilogram per day , for 3 days , followed by mefloquine at two doses totaling 25 mg per kilogram . We assessed in vitro and in vivo Plasmodium falciparum susceptibility , artesunate pharmacokinetics , and molecular markers of resistance . RESULTS We studied 40 patients in each of the two locations . The overall median parasite clearance times were 84 hours ( interquartile range , 60 to 96 ) in Pailin and 48 hours ( interquartile range , 36 to 66 ) in Wang Pha ( P<0.001 ) . Recrudescence confirmed by means of polymerase-chain-reaction assay occurred in 6 of 20 patients ( 30 % ) receiving artesunate monotherapy and 1 of 20 ( 5 % ) receiving artesunate-mefloquine therapy in Pailin , as compared with 2 of 20 ( 10 % ) and 1 of 20 ( 5 % ) , respectively , in Wang Pha ( P=0.31 ) . These markedly different parasitologic responses were not explained by differences in age , artesunate or dihydroartemisinin pharmacokinetics , results of isotopic in vitro sensitivity tests , or putative molecular correlates of P. falciparum drug resistance ( mutations or amplifications of the gene encoding a multidrug resistance protein [ PfMDR1 ] or mutations in the gene encoding sarco-endoplasmic reticulum calcium ATPase6 [ PfSERCA ] ) . Adverse events were mild and did not differ significantly between the two treatment groups . CONCLUSIONS P. falciparum has reduced in vivo susceptibility to artesunate in western Cambodia as compared with northwestern Thail and . Resistance is characterized by slow parasite clearance in vivo without corresponding reductions on conventional in vitro susceptibility testing . Containment measures are urgently needed . ( Clinical Trials.gov number , NCT00493363 , and Current Controlled Trials number , IS RCT N64835265 . ABSTRACT Imported malaria has been a great challenge for public health in China due to decreased locally transmitted cases and frequent exchange worldwide . Plasmodium falciparum has been mainly responsible for the increasing impact . Currently , artesunate plus amodiaquine , one of the artemisinin combination therapies recommended by the World Health Organization , has been mainly used against uncomplicated P. falciparum malaria in China . However , drug resistance marker polymorphism in returning migrant workers has not been demonstrated . Here , we have evaluated the prevalence of pfmdr1 and pfcrt polymorphisms , as well as the K13 propeller gene , a molecular marker of artemisinin resistance , in migrant workers returned from Ghana to Shanglin County , Guangxi Province , China , in 2013 . A total of 118 blood sample s were r and omly selected and used for the assay . Mutations of the pfmdr1 gene that covered codons 86 , 184 , 1034 , and 1246 were found in 11 isolates . Mutations at codon N86Y ( 9.7 % ) were more frequent than at others , and Y86Y184S1034D1246 was the most prevalent ( 63.6 % ) of the four haplotypes . Mutations of the pfcrt gene that covered codons 74 , 75 , and 76 were observed in 17 isolates , and M74N75T76 was common ( 70.6 % ) in three haplotypes . Eight different genotypes of the K13 propeller were first observed in 10 sample s in China , 2 synonymous mutations ( V487V and A627A ) and 6 nonsynonymous mutations . C580Y was the most prevalent ( 2.7 % ) in all the sample s. The data presented might be helpful for enrichment of molecular surveillance of antimalarial resistance and will be useful for developing and updating antimalarial guidance in China The emergence of resistance to artemisinin derivatives in Southeast Asia , manifested as delayed clearance of Plasmodium falciparum following treatment with artemisinins , is a major concern . Recently , the artemisinin resistance phenotype was attributed to mutations in portions of a P. falciparum gene ( PF3D7_1343700 ) encoding kelch ( K13 ) propeller domains , providing a molecular marker to monitor the spread of resistance . The P. falciparum cysteine protease falcipain-2 ( FP2 ; PF3D7_1115700 ) has been shown to contribute to artemisinin action , as hemoglobin degradation is required for potent drug activity , and a stop mutation in the FP2 gene was identified in parasites selected for artemisinin resistance . Although delayed parasite clearance after artemisinin-based combination therapy ( ACT ) has not yet been noted in Ug and a and ACTs remain highly efficacious , characterizing the diversity of these genes is important to assess the potential for resistance selection and to provide a baseline for future surveillance . We therefore sequenced the K13-propeller domain and FP2 gene in P. falciparum isolates from children previously treated with ACT in Ug and a , including sample s from 2006–7 ( n = 49 ) and from 2010–12 ( n = 175 ) . Using 3D7 as the reference genome , we identified 5 non-synonymous polymorphisms in the K13-propeller domain ( 133 isolates ) and 35 in FP2 ( 160 isolates ) ; these did not include the polymorphisms recently associated with resistance after in vitro selection or identified in isolates from Asia . The prevalence of K13-propeller and F Output:

Conclusion This review identified emergence of potential ART-resistance mediating k13 mutations in the African region . Diversity of mutations in pfkelch13 gene is highest in African region compared to SEA . Mutations outside the pfkelch13 propeller region associated with increased ART parasite clearance half-life occur in malaria-affected regions

MS214135

***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 determine whether a single high dose of vitamin A given to all children in communities with high mortality and malnutrition could affect mortality and to assess whether periodic community wide supplementation could be readily incorporated into an ongoing primary health programme . DESIGN --Opportunistic controlled trial . SETTING --Jumla district , Nepal . SUBJECTS -- All children aged under 5 years ; 3786 in eight subdistricts given single dose of vitamin A and 3411 in remaining eight subdistricts given no supplementation . MAIN OUTCOME MEASURES --Mortality and cause of death in the five months after supplementation . RESULTS --Risk of death for children aged 1 - 59 months in supplemented communities was 26 % lower ( relative risk 0.74 , 95 % confidence interval 0.55 to 0.99 ) than in unsupplemented communities . The reduction in mortality was greatest among children aged 6 - 11 months : death rate ( deaths/1000 child years at risk ) was 133.8 in supplemented children and 260.8 in unsupplemented children ( relative risk 0.51 , 0.30 to 0.89 ) . The death rate from diarrhoea was also reduced ( 63.5 supplemented v 97.5 unsupplemented ; relative risk 0.65 , 0.44 to 0.95 ) . The extra cost per death averted was about $ 11 . CONCLUSION --The results support a role for Vitamin A in increasing child survival . The supplementation programme was readily integrated with the ongoing community health programme at little extra cost The authors assessed the efficacy of the World Health Organization ( WHO ) recommendation of 200,000 IU of vitamin A in oil to treat acute non-xerophthalmic measles patients . Acute measles patients who did not require hospitalization were enrolled in a r and omized , double-masked , clinical trial of vitamin A ( n=90 ) versus placebo ( n=110 ) carried out in Ndola , Zambia , in 1991 . Measles-associated morbidity was defined by the presence of signs and symptoms of acute respiratory infection . Daily evaluations for the first 3 days were followed by weekly visits for a month at urban health centers . Baseline demographic , clinical , and biochemical characteristics were similar in both groups . Cross-sectional analysis of morbidity status , by group , at each weekly evaluation showed no significant differences until week 4 , when more placebo-treated patients had cough or pneumonia ( p=0.005 ) . However , longitudinal analysis , which looked at changes among individuals and controlled for initial health status , showed more equivocal results . The odds ratio for the development of pneumonia in patients with measles cough in vitamin A-treated subjects was 0.73 ( 95 % confidence interval ( Cl ) 0.30 - 1.80 ) . The odds ratio for the development of measles-associated cough or pneumonia in asymptomatic measles patients was 0.52 ( 95 % Cl 0.24 - 1.13 ) , in favor of vitamin A , but the odds ratio for failing to improve from pneumonia in vitamin A-treated subjects was 1.23 ( 95 % Cl 0.68 - 2.3 ) , a result in favor of placebo . These results suggest that the evidence for the efficacy of one dose of vitamin A in oil to prevent measles complications is not as strong as that previously shown for two 200,000 IU doses of water-miscible vitamin A , and that the WHO recommendation may need to be reexamined A prospect i ve study was conducted in slum children to determine the incidence of post-measles corneal disease and to clarify its relationship with nutritional status . A total of 318 cases of measles were identified over a period of 15 mo ; maximum incidence was observed for children between 1 - 2 yr . Most of the children showed weight loss and serum proteins decrease during the acute stage of measles . Corneal lesions were observed in 3 % of the children , and the lesions responded well to treatment . Serum vitamin A and RBP levels were significantly depressed during the acute stage of measles but were restored to normal 8 wk after recovery . There were no significant differences in the serum levels for those with and without eye lesions , which suggests that these lesions may not be mediated simply through the effect of infection on serum concentration of vitamin Incidence , duration , and severity of diarrhea and respiratory symptoms were monitored weekly for 1 y in 15,419 children 6 - 60 mo of age in a r and omized , placebo-controlled , masked clinical trial conducted in southern India . Half the children received weekly doses of 8.7 mumol ( 2500 microgram ) vitamin A and 46 mumol ( 20 mg ) vitamin E ( treated ) and the other half , 46 mumol vitamin E ( control ) . Medical and ocular examinations and anthropometric measurements were obtained before and after 52 wk of intervention . Ocular examinations also were obtained after 26 wk . Supplements were delivered weekly from calibrated dispenser bottles by community health volunteers who also recorded each mother 's recall of daily morbidity of her child during the previous week . Baseline characteristics of treated and control subjects were similar and documented a prevalence of 11 % xerophthalmia and 72 % undernutrition . Weekly treatment with the low-dose vitamin A supplement did not influence the incidence , severity , or duration of diarrhea or respiratory infections and did not influence linear or ponderal growth 450 villages in northern Sumatra were r and omly assigned to either participate in a vitamin A supplementation scheme ( n = 229 ) or serve for 1 year as a control ( n = 221 ) . 25 939 preschool children were examined at baseline and again 11 to 13 months later . Capsules containing 200 000 IU vitamin A were distributed to preschool children aged over 1 year by local volunteers 1 to 3 months after baseline enumeration and again 6 months later . Among children aged 12 - 71 months at baseline , mortality in control villages ( 75/10 231 , 7.3 per 1000 ) was 49 % greater than in those where supplements were given ( 53/10 919 , 4.9 per 1000 ) ( p less than 0.05 ) . The impact of vitamin A supplementation seemed to be greater in boys than in girls . These results support earlier observations linking mild vitamin A deficiency to increased mortality and suggest that supplements given to vitamin A deficient population s may decrease mortality by as much as 34 % Micronutrients ( zinc , vitamins A and E ) and related proteins ( retinol binding protein ( RBP ) , prealbumin , albumin ) were measured in the serum of African children with measles , and the changes induced in these by vitamin A supplementation ( offered in a r and omised , double blind , placebo controlled trial ) were studied . All these substances were significantly reduced early in the exanthem in measles patients as compared to controls ; they attained control values by day 8 after the rash , except for serum albumin which became normal by day 42 . Vitamin A and prealbumin levels on day 8 were significantly increased in the supplemented over the placebo group . Vitamin A levels in serum correlated with those of RBP , prealbumin and zinc . These findings strengthen the hypothesis that hyporetinemia during measles is the consequence of impaired mobilisation . Our results indicate that our patients did not have pre-existing low liver stores . Accordingly , the results obtained here provide rational support for the recommendation that vitamin A should be given to all children with severe measles , even in communities where vitamin A deficiency is not a recognised public health problem A cross-sectional study , a follow-up study , and an intervention trial were carried out to investigate the association between mild vitamin A deficiency and the occurrence of diarrhea and respiratory diseases . Cross-sectional analysis was performed among 1,772 children , aged 1 - 8 years , in the Sakon Nakhon province of northeastern Thail and . Children with a history of diarrhea or respiratory disease had lower levels of serum retinol and retinol-binding protein . Adjusted for age , sex , nutritional status , and level of urbanization , logistic regression using data for 877 children showed a negative association between serum retinol and both diarrhea and respiratory diseases . A follow-up three months later ( n = 146 children ) showed that children with deficient serum retinol ( less than 0.35 mumol/liter ) had a fourfold greater risk of respiratory disease ( p less than 0.01 ) . No relation was found for diarrhea . An intervention trial ( n = 166 children aged 1 - 5 years ) showed that , during 2 months of follow-up after administration of oral vitamin A ( 200,000 IU ) , the control group ( aged 3 - 5 years ) had a higher incidence of respiratory disease ( 2.9 times ) as well as diarrhea ( 3.1 times ) . Between 2 and 4 months , a significantly ( p less than 0.025 ) higher incidence of respiratory diseases ( 2.5 times ) could be observed in children aged 1 - 2 years . This study supports earlier reports on a greater risk of respiratory diseases and of diarrhea in mild vitamin A deficiency . Supplementation reduced the incidence of both diarrhea and respiratory disease for a period of at least 2 months Recently , the efficacy of oral vitamin A supplementation for measles and respiratory syncytial ( RSV ) infection has been evaluated in developing countries . However , in developed countries where vitamin A deficiency is little worth consideration , few studies have been conducted on the effect of vitamin A supplementation . The effect of oral vitamin A ( 100,000 IU ) supplementation was evaluated in 105 children with measles ( age 5 months to 4 years ) and in 96 children with RSV infection ( ages a month to 2.5 years ) in Fukushima , Japan . Comparisons were made of clinical signs , duration of hospitalization and complications between treated groups and non-treated groups . Treated group ( measles n = 47 , RSV n = 54 ) and non-treated groups ( measles n = 58 , RSV n = 42 ) had similar baseline characteristics . Patients with measles given a vitamin A supplementation had a shorter duration of cough ( 7.2 + /- 1.6 vs 9.2 + /- 1.8 days , p < 0.05 ) and patients with severe RSV infection given a vitamin A supplementation had a shorter duration of retraction ( 3.6 + /- 1.4 vs 5.3 + /- 0.8 days , p < 0.05 ) and wheezing ( 4.4 + /- 1.7 vs 6.3 + /- 1.5 days , p < 0.05 ) . Toxicities , including excess vomiting and bulging fontanel were not observed . Our findings may suggest the efficacy of oral vitamin A supplementation for measles and severe RSV infection , in children who have no malnutrition The effect of vitamin A supplementation on preschool child morbidity and mortality was assessed in a prospect i ve double-blind placebo-controlled study around Hyderabad , India . Every six months 200,000 IU vitamin A was given to 7691 children ( treatment group ) whereas 8084 children received a placebo ( control group ) . Morbidity and mortality data were collected every three months . Risk of respiratory infection was higher in children with mild xerophthalmia than in children with normal eyes . Vitamin A supplementation had no effect on morbidity status . Mortality rates were similar in the two groups ; it was highest in children who did not receive either vitamin A or placebo . The findings suggest that vitamin A supplementation alone may not reduce child mortality The effect of vitamin A supplementation on selected factors of immunity was tested in African children ( ages 4 to 24 months with complicated measles ) during a r and omized doubleblind intervention trial . Placebo ( n = 31 ) and treated groups ( n = 29 ) had similar baseline characteristics . The supplemented group had significant reductions in morbidity ( expressed as integrated morbidity scores ) during the acute ( Day 8 , P = 0.006 ) and chronic ( Day 42 , P = 0.02 ; 6 months ; P = 0.002 ) phases . In the treated group there was an increase in total number of lymphocytes ( Day 42 , P = 0.05 ) and measles IgG antibody concentrations ( Day 8 , P = 0.02 ) , both of which have consistently been previously shown to correlate more closely with outcome in measles than other immunologic , clinical and radiologic factors . Interleukin 2 and plasma complement values were unaffected by vitamin A supplementation . These findings reinforce results from animal studies that show that the pathways of vitamin A activity in decreasing morbidity and mortality are partly founded on selective immunopotentiation Although most studies on the effect of vitamin A supplementation have reported reductions in childhood mortality , the effects on morbidity are less clear . We have carried out two double-blind , r and omised , placebo-controlled trials of vitamin A supplementation in adjacent population s in northern Ghana to assess the impact on childhood morbidity and mortality . The Survival Study included 21,906 children aged 6 - 90 months in 185 geographical clusters , who were followed for up to 26 months . The Health Study included 1455 children aged 6 - 59 months , who were monitored Output:

We did not find evidence that a single dose of 200,000 IU of vitamin A per day , given in oil-based formulation in areas with low case fatality , was associated with reduced mortality among children with measles . However , there was evidence that the same dose given for two days was associated with a reduced risk of overall mortality and pneumonia specific mortality . REVIEW ER 'S CONCLUSIONS Although we did not find evidence that a single dose of 200,000 IU of vitamin A per day was associated with reduced mortality among children with measles , there was evidence that the same dose given for two days was associated with a reduced risk of overall mortality and pneumonia specific mortality . The effect was greater in children under the age of two years .

MS214136

***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: CONTEXT Existing therapies for major depression have a lag of onset of action of several weeks , result ing in considerable morbidity . Exploring pharmacological strategies that have rapid onset of antidepressant effects within a few days and that are sustained would have an enormous impact on patient care . Converging lines of evidence suggest the role of the glutamatergic system in the pathophysiology and treatment of mood disorders . OBJECTIVE To determine whether a rapid antidepressant effect can be achieved with an antagonist at the N-methyl-D-aspartate receptor in subjects with major depression . DESIGN A r and omized , placebo-controlled , double-blind crossover study from November 2004 to September 2005 . SETTING Mood Disorders Research Unit at the National Institute of Mental Health . Patients Eighteen subjects with DSM-IV major depression ( treatment resistant ) . INTERVENTIONS After a 2-week drug-free period , subjects were given an intravenous infusion of either ketamine hydrochloride ( 0.5 mg/kg ) or placebo on 2 test days , a week apart . Subjects were rated at baseline and at 40 , 80 , 110 , and 230 minutes and 1 , 2 , 3 , and 7 days postinfusion . Main Outcome Measure Changes in scores on the primary efficacy measure , the 21-item Hamilton Depression Rating Scale . RESULTS Subjects receiving ketamine showed significant improvement in depression compared with subjects receiving placebo within 110 minutes after injection , which remained significant throughout the following week . The effect size for the drug difference was very large ( d = 1.46 [ 95 % confidence interval , 0.91 - 2.01 ] ) after 24 hours and moderate to large ( d = 0.68 [ 95 % confidence interval , 0.13 - 1.23 ] ) after 1 week . Of the 17 subjects treated with ketamine , 71 % met response and 29 % met remission criteria the day following ketamine infusion . Thirty-five percent of subjects maintained response for at least 1 week . CONCLUSIONS Robust and rapid antidepressant effects result ed from a single intravenous dose of an N-methyl-D-aspartate antagonist ; onset occurred within 2 hours postinfusion and continued to remain significant for 1 week BACKGROUND The high-affinity N-methyl-D-aspartate ( NMDA ) antagonist ketamine exerts rapid antidepressant effects but has psychotomimetic properties . AZD6765 is a low-trapping NMDA channel blocker with low rates of associated psychotomimetic effects . This study investigated whether AZD6765 could produce rapid antidepressant effects in subjects with treatment-resistant major depressive disorder ( MDD ) . METHODS In this double-blind , r and omized , crossover , placebo-controlled study , 22 subjects with DSM-IV treatment-resistant MDD received a single infusion of either AZD6765 ( 150 mg ) or placebo on 2 test days 1 week apart . The primary outcome measure was the Montgomery-Åsberg Depression Rating Scale , which was used to rate overall depressive symptoms at baseline and 60 , 80 , 110 , and 230 min postinfusion and on Days 1 , 2 , 3 , and 7 postinfusion . Several secondary outcome measures were also used , including the Hamilton Depression Rating Scale . RESULTS Within 80 min , Montgomery-Åsberg Depression Rating Scale scores significantly improved in subjects receiving AZD6765 compared with placebo ; this improvement remained significant only through 110 min ( d = .40 ) . On the Hamilton Depression Rating Scale , a drug difference was found at 80 and 110 min and at Day 2 ( d = .49 ) . Overall , 32 % of subjects responded to AZD6765 , and 15 % responded to placebo at some point during the trial . No difference was observed between the groups with regard to psychotomimetic or dissociative adverse effects . CONCLUSIONS In patients with treatment-resistant MDD , a single intravenous dose of the low-trapping NMDA channel blocker AZD6765 was associated with rapid but short-lived antidepressant effects ; no psychotomimetic effects were observed Antagonism of N-methyl-D-aspartate glutamatergic receptors ( NMDAR ) may represent an effective antidepressant mechanism . D-cycloserine ( DCS ) is a partial agonist at the NMDAR-associated glycine modulatory site that at high doses acts as a functional NMDAR antagonist . Twenty-six treatment-resistant major depressive disorder patients participated in a double blind , placebo-controlled , 6-wk parallel group trial with a gradually titrated high dose ( 1000 mg/d ) of DCS added to their antidepressant medication . DCS treatment was well tolerated , had no psychotomimetic effects and led to improvement in depression symptoms as measured by Hamilton Depression Rating Scale ( HAMD ; p = 0.005 ) and Beck Depression Inventory ( p = 0.046 ) . Of the 13 subjects treated with DCS , 54 % had a ≥ 50 % HAMD score reduction vs. 15 % of the 13 patients r and omized to placebo ( p = 0.039 ) . A significant ( p = 0.043 ) treatment × pre-treatment glycine serum levels interaction was registered . These findings indicate that NMDAR glycine site antagonism may be a cost-effective target for development of mechanistically novel antidepressants . Larger-sized DCS trials are warranted Accumulating evidence suggests that N-methyl-d-aspartate receptor ( NMDAR ) antagonists ( e.g. ketamine ) may exert rapid antidepressant effects in MDD patients . In the present study , we evaluated the rapid antidepressant effects of ketamine compared with the electroconvulsive therapy ( ECT ) in hospitalized patients with MDD . In this blind , r and omized study , 18 patients with DSM-IV MDD were divided into two groups which received either three intravenous infusions of ketamine hydrochloride ( 0.5 mg/kg over 45 min ) or ECT on 3 test days ( every 48 h ) . The primary outcome measure was the Beck Depression Inventory ( BDI ) and Hamilton Depression Rating Scale ( HDRS ) , which was used to rate overall depressive symptoms at baseline , 24 h after each treatment , 72 h and one week after the last ( third ) ketamine or ECT . Within 24 h , depressive symptoms significantly improved in subjects receiving the first dose of ketamine compared with ECT group . Compared to baseline level , this improvement remained significant throughout the study . Depressive symptoms after the second dose ketamine was also lower than the second ECT . This study showed that ketamine is as effective as ECT in improving depressive symptoms in MDD patients and have more rapid antidepressant effects compared with the ECT 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 We investigated whether ketamine is suitable for depressed patients who had undergone orthopedic surgery . We studied 70 patients with major depression and 25 patients as the control ( Group C ) . The depressed patients were divided r and omly into two groups ; patients in Group A ( n = 35 ) were induced with propofol , fentanyl , and ketamine and patients in Group B ( n = 35 ) were induced with propofol and fentanyl , and all patients were maintained with 1.5%–2.0 % isoflurane plus nitrous oxide . The mean Hamilton Depression Rating ( HDR ) score was 12.7 ± 5.4 for Group A and 12.3 ± 6.0 for Group B 2 days before surgery and 9.9 ± 4.1 for Group A and 14.4 ± 3.8 for Group B 1 day after surgery . The HDR score in Group A 1 day after surgery was significantly ( P < 0.05 ) lower than that in Group B. The HDR score in Group C was 4.2 ± 1.7 2 days before surgery and 4.8 ± 1.6 1 day after surgery . Depressed mood , suicidal tendencies , somatic anxiety , and hypochondriasis significantly decreased in Group A as compared with Group B. Postoperative pain scores in Group A at 8 and 16 h after the end of anesthesia were 26.6 ± 8.7 and 24.9 ± 8.2 , respectively , which were significantly ( P < 0.05 ) lower than 34.3 ± 12.0 and 31.1 ± 8.8 in Group B. In conclusion , small-dose ketamine improved the postoperative depressive state and relieved postoperative pain in depressed patients OBJECTIVE Ketamine , a glutamate N-methyl-d-aspartate ( NMDA ) receptor antagonist , has shown rapid antidepressant effects , but small study groups and inadequate control conditions in prior studies have precluded a definitive conclusion . The authors evaluated the rapid antidepressant efficacy of ketamine in a large group of patients with treatment-resistant major depression . METHOD This was a two-site , parallel-arm , r and omized controlled trial of a single infusion of ketamine compared to an active placebo control condition , the anesthetic midazolam . Patients with treatment-resistant major depression experiencing a major depressive episode were r and omly assigned under double-blind conditions to receive a single intravenous infusion of ketamine or midazolam in a 2:1 ratio ( N=73 ) . The primary outcome was change in depression severity 24 hours after drug administration , as assessed by the Montgomery-Åsberg Depression Rating Scale ( MADRS ) . RESULTS The ketamine group had greater improvement in the MADRS score than the midazolam group 24 hours after treatment . After adjustment for baseline scores and site , the MADRS score was lower in the ketamine group than in the midazolam group by 7.95 points ( 95 % confidence interval [ CI ] , 3.20 to 12.71 ) . The likelihood of response at 24 hours was greater with ketamine than with midazolam ( odds ratio , 2.18 ; 95 % CI , 1.21 to 4.14 ) , with response rates of 64 % and 28 % , respectively . CONCLUSIONS Ketamine demonstrated rapid antidepressant effects in an optimized study design , further supporting NMDA receptor modulation as a novel mechanism for accelerated improvement in severe and chronic forms of depression . More information on response durability and safety is required before implementation in clinical practice BACKGROUND Currently , no pharmacological treatments for bipolar depression exist that exert rapid ( within hours ) antidepressant or antisuicidal effects . We previously reported that intravenous administration of the N-methyl-D-aspartate antagonist ketamine produced rapid antidepressant effects in patients with treatment-resistant bipolar depression . The present study sought to replicate this finding in an independent sample . METHODS In this double-blind , r and omized , crossover , placebo-controlled study , 15 subjects with DSM-IV bipolar I or II depression maintained on therapeutic levels of lithium or valproate received a single intravenous infusion of either ketamine hydrochloride ( .5 mg/kg ) or placebo on 2 test days 2 weeks apart . The primary outcome measure was the Montgomery-Asberg Depression Rating Scale , which was used to rate overall depressive symptoms at baseline ; at 40 , 80 , 110 , and 230 minutes postinfusion ; and on days 1 , 2 , 3 , 7 , 10 , and 14 postinfusion . RESULTS Within 40 minutes , depressive symptoms , as well as suicidal ideation , significantly improved in subjects receiving ketamine compared with placebo ( d = .89 , 95 % confidence interval = .61 - 1.16 , and .98 , 95 % confidence interval = .64 - 1.33 , respectively ) ; this improvement remained significant through day 3 . Seventy-nine percent of subjects responded to ketamine and 0 % responded to placebo at some point during the trial . The most common side effect was dissociative symptoms , which occurred only at the 40-minute time point . CONCLUSIONS This study replicated our previous finding that patients with bipolar depression who received a single ketamine infusion experienced a rapid and robust antidepressant response . In addition , we found that ketamine rapidly improved suicidal ideation in these patients The purpose of this study was to develop an instrument for the measurement of present-state dissociative symptoms , the Clinician Administered Dissociative States Scale ( CADSS ) . Reported here are interrater reliability and internal consistency of the CADSS , validity as assessed by comparisons with other instruments for the assessment of dissociation , and sensitivity of the CADSS to discriminate patients with dissociative disorders from patients with other psychiatric disorders and healthy subjects . Initial analyses indicated good interrater reliability and construct validity for the CADSS . Scores on the CADSS discriminated patients with dissociative disorders from the other groups Ketamine produces Output:

Ketamine was associated with transient psychotomimetic effects , but no persistent psychosis or affective switches . CONCLUSION Our meta- analysis suggests that single administrations ketamine are efficacious in the rapid treatment of unipolar and bipolar depression .

MS214137

***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 Recent reports have drawn attention to the importance of pulse pressure as a predictor of cardiovascular events . Pulse pressure is used neither by clinicians nor by guidelines to define treatable levels of blood pressure . METHODS In the Cardiovascular Health Study , 5888 adults 65 years and older were recruited from 4 US centers . At baseline in 1989 - 1990 , participants underwent an extensive examination , and all subsequent cardiovascular events were ascertained and classified . RESULTS At baseline , 1961 men and 2941 women were at risk for an incident myocardial infa rct ion or stroke . During follow-up that averaged 6.7 years , 572 subjects had a coronary event , 385 had a stroke , and 896 died . After adjustment for potential confounders , systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP ) , and pulse pressure were directly associated with the risk of incident myocardial infa rct ion and stroke . Only SBP was associated with total mortality . Importantly , SBP was a better predictor of cardiovascular events than DBP or pulse pressure . In the adjusted model for myocardial infa rct ion , a 1-SD change in SBP , DBP , and pulse pressure was associated with hazard ratios ( 95 % confidence intervals ) of 1.24 ( 1.15 - 1.35 ) , 1.13 ( 1.04 - 1.22 ) , and 1.21 ( 1.12 - 1.31 ) , respectively ; and adding pulse pressure or DBP to the model did not improve the fit . For stroke , the hazard ratios ( 95 % confidence intervals ) were 1.34 ( 1.21 - 1.47 ) with SBP , 1.29 ( 1.17 - 1.42 ) with DBP , and 1.21 ( 1.10 - 1.34 ) with pulse pressure . The association between blood pressure level and cardiovascular disease risk was generally linear ; specifically , there was no evidence of a J-shaped relationship . In those with treated hypertension , the hazard ratios for the association of SBP with the risks for myocardial infa rct ion and stroke were less pronounced than in those without treated hypertension . CONCLUSION In this population -based study of older adults , although all measures of blood pressure were strongly and directly related to the risk of coronary and cerebrovascular events , SBP was the best single predictor of cardiovascular events Background In patients with cardiovascular disease , a high pulse pressure is related to an increased risk of cardiovascular events but in patients with advanced heart failure , a low pulse pressure is predictive of adverse ( cardiovascular ) events . Aim We studied the prognostic importance of pulse pressure in a group of post-myocardial infa rct ion patients , with and without signs and symptoms of heart failure . Subjects had been r and omised in the CAPRICORN clinical trial , and followed up for a mean of 1.3 years . Methods Blood pressure was measured in 1,955 patients with a left ventricular ejection fraction ≤40 % , between 3 and 21 days post myocardial infa rct ion . Cox proportional survival models were reproduced for those with Killip Class I ( n = 1342 ) versus classes II/III/IV heart failure ( n = 613 ) . Results Overall mean ( SD ) age was 63 ( 12 ) years , mean ( SD ) left ventricular ejection fraction 33(6)% , mean ( SD ) baseline blood pressure was 121 (17)/74 ( 10 ) mmHg and most ( 73 % ) were male . In patients with Killip Class 1 , pulse pressure was not predictive for any outcome . However , in patients with Killip Class II – IV , a low pulse pressure independently predicted all cause mortality ( HR 0.83 per 10 mmHg , CI 0.71–0.98 , p = 0.025 ) , cardiovascular mortality ( HR 0.83 per 10 mmHg , CI 0.70–0.98 , p = 0.025 ) and sudden death ( HR 0.77 per 10 mmHg , CI 0.60–1.00 , p = 0.047 ) . A lower pulse pressure did not predict hospitalisation for worsening heart failure . Conclusion A low pulse pressure is an independent predictor of mortality in subjects with depressed left ventricular ejection fraction after a recent myocardial infa rct ion and evidence of Killip Class II – IV heart failure Abstract Objective : This study aims to develop and vali date a stroke risk model incorporating pulse pressure ( PP ) as a potential risk factor . Recent evidence suggests that PP , defined as the difference between systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) , could be an incremental risk factor beyond SBP . Methods : Electronic health records ( EHRs ) of hypertensive patients from a US integrated health delivery system were analyzed ( January 2004 to May 2012 ) . Patients with ≥1 PP reading and ≥6 months of observation prior to the first diagnosis of hypertension were r and omly split into development ( two-thirds of sample ) and validation ( one-third of sample ) data sets . Stroke events were identified using ICD-9-CM 433.xx–436.xx . Cox proportional hazards models assessed time to first stroke event within 3 years of first hypertension diagnosis based on baseline risk factors , including PP , age , gender , diabetes , and cardiac comorbidities . The optimal model was selected using the least absolute shrinkage and selection operator ( LASSO ) ; performance was evaluated by the c-statistic . Results : Among 34,797 patients selected ( mean age 59.3 years , 48 % male ) , 4272 patients ( 12.3 % ) had a stroke . PP was higher among patients who developed stroke ( mean [ SD ] PP , stroke : 02.0 [ 15.3 ] mmHg ; non-stroke : 58.1 [ 14.0 ] mmHg , p < 0.001 ) . The best performing risk model ( c-statistic , development : 0.730 ; validation : 0.729 ) included PP ( hazard ratio per mmHg increase : 1.0037 , p < 0.001 ) as a significant risk factor . Limitations : This study was subject to limitations similar to other studies using EHRs . Only patient encounters occurring within the single healthcare network were captured in the data source . Though the model was tested internally , external validation ( using a separate data source ) would help assess the model ’s generalizability and calibration . Conclusions : This stroke risk model shows that greater PP is a significant predictive factor for increased stroke risk , even in the presence of known risk factors . PP should be considered by practitioners along with established risk factors in stroke treatment strategies Objective Although pulse pressure has been recognized a risk factor for coronary heart disease in both middle-aged and elderly , and for stroke in the elderly , the contribution of pulse pressure to the risk of stroke among the middle-aged is uncertain . Methods A total of 33 372 participants ( 11 684 men and 21 688 women aged 40–69 years ) living in communities , free of prior diagnosis of cardiovascular disease and cancer , completed health check-up examination . They were followed from 1990–1992 to the end of 2004 in the Japan public health center-based prospect i ve study on cancer and cardiovascular disease . After 422 864 person-years of follow-up , 1081 incident strokes ( 559 men and 522 women ) were documented . Results Pulse pressure was positively associated with risk of stroke as was systolic and diastolic blood pressures . The multivariable hazard ratio of total stroke associated with a 1-SD increment ( 13.2 mmHg ) of pulse pressure was 1.14 ( 1.05–1.24 ) . The excess risk was observed for the stratum of systolic blood pressure below 140 mmHg , but not of higher systolic blood pressure levels after adjustment for diastolic blood pressure and other potential confounding factors ; the multivariable hazard ratio of stroke associated with a 1-SD increment of pulse pressure was 1.32 ( 1.07–1.64 ) among persons with normal systolic blood pressure levels . Conclusions Pulse pressure is a risk factor for stroke among normotensive individuals with systolic blood pressure below 140 mmHg , which suggests that pulse pressure may be useful to predict the risk of stroke among middle-aged nonsystolic hypertensive patients Objective : To evaluate which blood pressure measure is the best predictor of risk of total , ischemic , and hemorrhagic stroke . Methods : The authors used a prospect i ve cohort study among 11,466 men followed for incident stroke during a median of 19.4 years in the Physicians ' Health Study . Systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) were self-reported . They calculated relative risks ( RRs ) and 95 % CIs for total , ischemic , and hemorrhagic stroke using Cox proportional hazards models . Model fit was compared using the χ2 test statistic from likelihood ratio tests . Results : During follow-up , 508 strokes occurred ( 411 ischemic , 89 hemorrhagic , and eight of unknown etiology ) . For each 10-mm Hg increase in SBP , the multivariable RRs were 1.31 ( 95 % CI : 1.20 to 1.42 ) for total stroke , 1.28 ( 95 % CI : 1.16 to 1.40 ) for ischemic stroke , and 1.38 ( 95 % CI : 1.13 to 1.68 ) for hemorrhagic stroke . Although DBP , pulse pressure , and mean arterial pressure were all significant predictors of stroke risk , none was a significantly better predictor than SBP alone . Adding DBP did not significantly improve the model fit of SBP alone for any stroke type . Conclusion : In this large cohort of initially healthy men , systolic blood pressure was a consistent and significant predictor of total , ischemic , and hemorrhagic stroke . Systolic blood pressure alone was the only measure necessary to predict risk of total stroke or its major subtypes Background and Purpose — The purpose of this prospect i ve cohort study was to investigate associations between stroke and blood pressure ( BP ) indices ( systolic BP [ SBP ] , diastolic BP [ DBP ] , mean BP , and pulse pressure [ PP ] ) determined by home BP measurement . Methods — Associations between stroke and BP indices were examined in a rural Japanese population . Home BP data of 2369 subjects ( 40 % men ) ≥35 years of age ( mean , 59 years ) without a history of stroke were obtained . Associations between stroke and each index were determined using Cox proportional hazards regression and the likelihood ratio ( LR ) test . Results — During follow-up ( mean , 11.7 years ) , 238 strokes occurred . The LR test showed that SBP and mean BP were significantly more strongly associated with total and ischemic stroke than DBP and PP ( LR & khgr;2 ≥9.3 , P<0.01 for SBP/mean BP , LR & khgr;2 ≤3.8 , P≥0.05 for DBP/PP ) . SBP tended to be more strongly associated with total/ischemic stroke than mean BP ( LR & khgr;2=3.8 , P=0.05 for SBP , LR & khgr;2 ≤0.2 , P>0.6 for mean BP ) . PP tended to be slightly more strongly associated with ischemic stroke than DBP ( LR & khgr;2=7.5 , P<0.01 for DBP , LR & khgr;2=9.3 , P<0.01 for PP ) , whereas DBP was significantly more strongly associated with hemorrhagic stroke than PP ( LR & khgr;2=9.2 , P<0.01 for DBP , LR & khgr;2=2.5 , P=0.01 for PP ) . Conclusion — PP obtained from home BP measurements was weakly associated with stroke , whereas SBP showed the strongest association . Additionally , DBP and PP may be associated with different stroke types Background Our objective was to test the hypothesis that elevated blood pressure ( BP ) is associated with increased risk of stroke , bleeding and death in patients with incident heart failure ( HF ) . Methods We conducted a prospect i ve cohort study among subjects who were participants in the Diet , Cancer and Health study , born in Denmark , aged 50–64 years at recruitment . We assessed stroke ( ischemic stroke or systemic embolic events ) , major bleeding , death and the composite endpoint according to degree of BP control in patients with incident HF . BP was assessed prior to HF at cohort entry . Results Of the whole cohort of 55,748 subjects , n = 2159 ( 35 % female ) had incident HF , of which 12 % had treatment for hypertension . Median follow-up after incident HF was 3.5 years . High systolic ( SBP ) , diastolic ( DBP ) and pulse ( PP ) pressures were associated with an increased risk of stroke , major bleeding and the composite endpoint . For death and stroke/death , the relation appeared U-shaped for SBP and DBP . When comparing the highest quartile group ( Q4 ) to first quartile group ( Q1 ) , SBP ( Q4 : SBP > 163 mmHg ) was Output:

Conclusions Current data confirms that PP is an independent risk factor for stroke but is not a predictor of mortality

MS214138

***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 Whether there is an association between depression at the time of acute myocardial infa rct ion and subsequent risk of cardiac complications and death remains controversial . Most studies of this risk factor have been limited to patients of single institutions , and this might account for the varying results . We prospect ively evaluated patients admitted to 5 tertiary care and 5 community hospitals and followed them for 1 year to measure the prevalence and prognostic impact of depressive symptoms after acute myocardial infa rct ion . METHODS Patients were recruited for the study by trained nurse interviewers who had documented acute myocardial infa rct ion within 2 - 3 days of admission . The nurses collected information from the medical records and asked study subjects to complete the Beck Depression Inventory question naire during their stay in hospital and using a mailed question naire 30 days , 6 months and 1 year later . We obtained information on vital status for patients lost to follow-up from a central death registry . RESULTS Of the 587 study subjects , 550 ( 94 % ) completed the Beck Depression Inventory at baseline and 191 ( 35 % ) had a score of 10 or more , indicating at least mild depression . Rates of depression did not vary over the follow-up period and were similar among patients admitted to tertiary care or community hospitals . Depressed patients were more likely to undergo catheterization ( 57 % v. 47 % , 95 % confidence interval [ CI ] around the difference 0.1%-19.6 % ) and were more likely to undergo percutaneous coronary intervention ( 32 % v. 24 % , 95 % CI around the difference 0.1%-16.2 % ) within 30 days of first admission to hospital . Patients with depression on admission had higher rates of a composite of cardiac complications , including recurrent ischemia , infa rct ion or congestive heart failure during their first stay in hospital or readmission for angina , recurrent acute myocardial infa rct ion , congestive heart failure or arrhythmia ( adjusted hazard ratio 1.4 , 95 % CI 1.05 - 1.86 ) , compared with patients who were not depressed on admission . After 1 year , death rates were higher among patients who were depressed at admission ( 30 patients , 16 % ) compared with nondepressed patients ( 28 patients , 8 % ) , although the difference was not statistically significant ( hazard ratio 1.3 , 95 % CI 0.59 - 3.05 ) . INTERPRETATION Depressive symptoms are common after acute myocardial infa rct ion and are associated with a slight increase in risk of in-hospital catheterization and angiography and readmission because of cardiac complications . Death was infrequent , with no statistically significant difference between the 2 groups Background —Few data are available on the impact of heart failure ( HF ) across all types of acute coronary syndromes ( ACS ) . Methods and Results —The Global Registry of Acute Coronary Events ( GRACE ) is a prospect i ve study of patients hospitalized with ACS . Data from 16 166 patients were analyzed : 13 707 patients without prior HF or cardiogenic shock at presentation were identified . Of these , 1778 ( 13 % ) had an admission diagnosis of HF ( Killip class II or III ) . HF on admission was associated with a marked increase in mortality rates during hospitalization ( 12.0 % versus 2.9 % [ with versus without HF ] , P < 0.0001 ) and at 6 months after discharge ( 8.5 % versus 2.8 % , P < 0.0001 ) . Of note , HF increased mortality rates in patients with unstable angina ( defined as ACS with normal biochemical markers of necrosis ; mortality rates : 6.7 % with versus 1.6 % without HF at admission , P < 0.0001 ) . By logistic regression analysis , admission HF was an independent predictor of hospital death ( odds ratio , 2.2 ; P < 0.0001 ) . Admission HF was associated with longer hospital stay and higher readmission rates . Patients with HF had lower rates of catheterization and percutaneous cardiac intervention , and fewer received & bgr;-blockers and statins . Hospital development of HF ( versus HF on presentation ) was associated with an even higher in-hospital mortality rate ( 17.8 % versus 12.0 % , P < 0.0001 ) . In patients with HF , in-hospital revascularization was associated with lower 6-month death rates ( 14.0 % versus 23.7 % , P < 0.0001 ; adjusted hazard ratio , 0.5 ; 95 % CI , 0.37 to 0.68 , P < 0.0001 ) . Conclusions —In this observational registry , heart failure was associated with reduced hospital and 6-month survival across all ACS subsets , including patients with normal markers of necrosis . More aggressive treatment of these patients may be warranted to improve prognosis CONTEXT The prevalence and consequences of financial barriers to health care services and medications are not well documented for patients with an acute myocardial infa rct ion ( AMI ) . OBJECTIVE To measure the baseline prevalence of self-reported financial barriers to health care services or medication ( as defined by avoidance due to cost ) among individuals following AMI and their association with subsequent health care outcomes . DESIGN , SETTING , AND PARTICIPANTS The Prospect i ve Registry Evaluating Myocardial Infa rct ion : Event and Recovery ( PREMIER ) , an observational , multicenter US study of patients with AMI over 12 months in 2498 individuals enrolled from January 2003 through June 2004 . MAIN OUTCOME MEASURES Health status symptoms ( Seattle Angina Question naire [ SAQ ] ) , overall health status function ( Short Form-12 ) , and rehospitalization . RESULTS The prevalence of self-reported financial barriers to health care services or medication was 18.1 % and 12.9 % , respectively . Among individuals who reported financial barriers to health care services or medication , 68.9 % and 68.5 % , respectively , were insured . At 1-year follow-up , individuals with financial barriers to health care services were more likely to have lower SAQ quality -of-life score ( 77.9 vs 86.2 ; adjusted mean difference= -4.0 ; 95 % confidence interval [ CI ] , -6.3 to -1.8 ) , and increased rates of all-cause rehospitalization ( 49.3 % vs 38.1 % ; adjusted hazard ratio [ HR ] , 1.3 ; 95 % CI , 1.1 - 1.5 ) and cardiac rehospitalization ( 25.7 % vs 17.7 % ; adjusted HR , 1.3 ; 95 % CI , 1.0 - 1.6 ) . At 1-year follow-up , individuals with financial barriers to medication were more likely to have angina ( 34.9 % vs 17.9 % ; adjusted odds ratio , 1.55 ; 95 % CI , 1.1 - 2.2 ) , lower SAQ quality -of-life score ( 74.0 vs 86.1 ; adjusted mean difference = -7.6 ; 95 % CI , -10.2 to -4.9 ) , and increased rates of all-cause rehospitalization ( 57.0 % vs 37.8 % ; risk-adjusted HR , 1.5 ; 95 % CI , 1.2 - 1.8 ) and cardiac rehospitalization ( 33.7 % vs 17.3 % ; adjusted HR , 1.7 ; 95 % CI , 1.3 - 2.2 ) . CONCLUSION Financial barriers to health care services and medications are associated with worse recovery after AMI , manifested as more angina , poorer quality of life , and higher risk of rehospitalization Background — The role of the vasopressin system after acute myocardial infa rct ion is unclear . Copeptin , the C-terminal part of the vasopressin prohormone , is secreted stoichiometrically with vasopressin . We compared the prognostic value of copeptin and an established marker , N-terminal pro-B-type natriuretic peptide ( NTproBNP ) , after acute myocardial infa rct ion . Methods and Results — In this prospect i ve single-hospital study , we recruited 980 consecutive post – acute myocardial infa rct ion patients ( 718 men , median [ range ] age 66 [ 24 to 95 ] years ) , with follow-up over 342 ( range 0 to 764 ) days . Plasma copeptin was highest on admission ( n=132 , P<0.001 , day 1 versus days 2 to 5 ) and reached a plateau at days 3 to 5 . In the 980 patients , copeptin ( measured at days 3 to 5 ) was elevated in patients who died ( n=101 ) or were readmitted with heart failure ( n=49 ) compared with survivors ( median [ range ] 18.5 [ 0.6 to 441.0 ] versus 6.5 [ 0.3 to 267.0 ] pmol/L , P<0.0005 ) . With logistic regression analysis , copeptin ( odds ratio , 4.14 , P<0.0005 ) and NTproBNP ( odds ratio , 2.26 , P<0.003 ) were significant independent predictors of death or heart failure at 60 days . The area under the receiver operating characteristic curves for copeptin ( 0.75 ) and NTproBNP ( 0.76 ) were similar . The logistic model with both markers yielded a larger area under the curve ( 0.84 ) than for NTproBNP ( P<0.013 ) or copeptin ( P<0.003 ) alone , respectively . Cox modeling predicted death or heart failure with both biomarkers ( log copeptin [ hazard ratio , 2.33 ] , log NTproBNP [ hazard ratio , 2.70 ] ) . In patients stratified by NTproBNP ( above the median of ≈900 pmol/L ) , copeptin above the median ( ≈7 pmol/L ) was associated with poorer outcome ( P<0.0005 ) . Findings were similar for death and heart failure as individual end points . Conclusions — The vasopressin system is activated after acute myocardial infa rct ion . Copeptin may predict adverse outcome , especially in those with an elevated NTproBNP ( more than ≈900 pmol/L ) BACKGROUND Disease management programs ( DMPs ) that use multidisciplinary teams and specialized clinics reduce hospital admissions and improve quality of life and functional status . Evaluations of cardiac DMPs delivered by home health nurses are required . METHODS Between August 1999 and August 2000 we identified consecutive patients admitted to hospital with elevated cardiac enzymes . Patients who agreed were r and omly assigned to participate in a DMP or to receive usual care . The DMP included 6 home visits by a cardiac-trained nurse , a st and ardized nurses ' checklist , referral criteria for specialty care , communication with the family physician and patient education . We measured readmission days per 1000 follow-up days for angina , congestive heart failure ( CHF ) and chronic obstructive pulmonary disease ( COPD ) ; all-cause readmission days ; and provincial cl aims for emergency department visits , physician visits , diagnostic or therapeutic services and laboratory services . RESULTS We screened 715 consecutive patients admitted with elevated cardiac markers between August 1999 and August 2000 . Of those screened 71 DMP and 75 usual care patients met the diagnostic criteria for myocardial infa rct ion , were eligible for visits from a home health nurse and consented to participate in the study . Readmission days for angina , CHF and COPD per 1000 follow-up days were significantly higher for usual care patients than for DMP patients ( incidence density ratio [ IDR ] = 1.59 , 95 % confidence interval [ CI ] 1.27 - 2.00 , p < 0.001 ) . All-cause readmission days per 1000 follow-up days were significantly higher for usual care patients than for DMP patients ( IDR = 1.53 , 95 % CI 1.37 - 1.71 , p < 0.001 ) . The difference in emergency department encounters per 1000 follow-up days was significant ( IDR = 2.08 , 95 % CI 1.56 - 2.77 , p < 0.001 ) . During the first 25 days after discharge , there were significantly fewer provincial cl aims su bmi tted for DMP patients than for usual care patients for emergency department visits ( p = 0.007 ) , diagnostic or therapeutic services ( p = 0.012 ) and laboratory services ( p = 0.007 ) . INTERPRETATION The results provide evidence that an appropriately developed and implemented community-based inner-city DMP delivered by home health nurses has a positive impact on patient outcomes Although chronic obstructive pulmonary disease ( COPD ) is common in patients with myocardial infa rct ion ( MI ) , its association with long-term mortality after MI is controversial and little is known about its influence on patients ' health status ( symptoms , Output:

Patient characteristics may be important predictors of AMI readmission ; however , few variables were consistently identified .

MS214139

***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 The aim of this study was to evaluate the clinical and microbiological effects of scaling and root planing ( SRP ) alone or combined with metronidazole ( MTZ ) or with MTZ and amoxicillin ( AMX ) in the treatment of smokers with chronic periodontitis . METHODS A double-blind , placebo-controlled , r and omized clinical trial was conducted in 43 subjects who received SRP alone ( n=15 ) or combined with MTZ ( 400 mg 3 x per day , n=14 ) or with MTZ+AMX ( 500 mg 3 x per day , n=14 ) for 14 days . Clinical and microbiological examinations were performed at baseline and 3 months post-therapy . Subgingival sample s were analysed by checkerboard DNA-DNA hybridization . RESULTS Subjects receiving MTZ+AMX showed the greatest improvements in mean probing depth and clinical attachment level . Both antibiotic therapies led to additional clinical benefits over SRP alone in initially shallow , intermediate , and deep sites . The SRP+MTZ+AMX therapy led to the most beneficial changes in the subgingival microbial profile . These subjects showed significant reductions in the mean counts and proportions of periodontal pathogens such as Tannerella forsythia , Porphyromonas gingivalis and Treponema denticola , and the greatest increase in proportions of host-compatible species . CONCLUSION Significant advantages are observed when systemic antibiotics are combined with SRP in the treatment of smokers with chronic periodontitis . The greatest benefits in clinical and microbiological parameters are achieved with the use of SRP+MTZ+AMX The aim of the present study was to analyze the effect of systemic antimicrobial therapy and mechanical plaque control in patients with recurrent periodontal disease . 9 patients volunteered for the combined therapy . At a baseline examination they were r and omly distributed into 2 groups , one given tetracycline therapy for 2 weeks and the other metronidazole therapy for 1 week . A mechanical plaque control program comprising oral hygiene training , professional cleaning of all teeth and subgingival debridement at diseased sites was carried out at the baseline examination and at all recall visits , i.e. once every month during the first 6 months and then after 9 , 12 , and 18 months . The results demonstrated clinical ly and microbiologically that a combination of an initial antimicrobial and a continuous systematic mechanical plaque control program may be a valuable therapeutic approach in a strictly selected group of refractory patients . Recurrent periodontal lesions which still displayed severe inflammation despite renewed conventional therapy showed a marked reduction in probing depths , bleeding and suppuration from the pockets , and further , a reduced presence of spirochetes and motile rods during the trial . The results indicate that the level and longevity of success is also related to whether or not self-performed oral hygiene measures are sufficiently carried out . No superior effect of the combined program could be observed in cooperating patients receiving tetracycline as compared with those given metronidazole Aim Find the periodontal treatment that best maintained clinical results over time evaluated by changes in pocket depth ( PD ) and clinical attachment level ( CAL ) . Methods 229 patients with chronic periodontitis from USA ( n=134 ) and Sweden ( n=95 ) were r and omly assigned to eight groups receiving 1 scaling+root planing ( SRP ) alone or combined with 2 surgery (SURG)+systemic amoxicillin (AMOX)+systemic metronidazole ( MET ) ; 3 SURG+local tetracycline ( TET ) ; 4 SURG ; 5 AMOX+MET+TET ; 6 AMOX+MET ; 7 TET ; and 8 SURG+AMOX+MET+TET . Antibiotics were given immediately after SRP . Plaque , gingival redness , bleeding on probing , suppuration , PD , and CAL were recorded at baseline and after 3 , 6 , 12 , 18 , and 24 months . Treatment effects were evaluated by linear multilevel regression and logistic multilevel regression models . We considered only data from sites with a baseline PD of at least 5 mm of 187 patients completing the study . Results Surgically treated patients experienced most CAL loss . Adjunctive therapy including SURG was most effective in reducing PD . Combining SURG with AMOX , MET , and TET gave significant clinical benefits . Past and current smoking habits were significant predictors of deeper PD . Only current smoking was a significant predictor of CAL loss . Bleeding , accumulation of plaque , gingival redness , and suppuration were significant predictors of further CAL loss and deeper PD . Conclusions Both surgical and non-surgical therapies can be used to arrest chronic periodontitis . SURG+AMOX+MET+TET gave best maintenance of clinical results Periodontitis , a common cause of tooth loss in adult population s , is an inflammatory response to the overgrowth of anaerobic organisms such as spirochetes and bacteroides and , in some cases , micro-aerophilic organisms in the subgingival plaque . In the present investigation , using a double-blind clinical design , we sought to determine whether 1 week of metronidazole treatment plus debridement of the tooth surfaces was superior to 1 week of placebo treatment plus debridement ( positive control ) in reducing the subsequent amount of periodontal surgery given to the patients . Thirty-nine patients were r and omly assigned to either the metronidazole or placebo ( positive control ) groups . All patients were given the necessary scaling and root planing and were unsupervised in their usage of the medication . After the completion of this treatment , they were reexamined and it was found that the metronidazole regimen caused a significant reduction in surgical needs of about 5 teeth per patient compared to the positive control ( difference before and after treatment 8.3 + /- 6.8 teeth metronidazole versus 2.9 + /- 4.8 positive control , P = 0.007 ) . The difference between groups was maintained during the 2 to 3 years ' recall period . Metronidazole had a significant effect on the site specific reduction of spirochetes : 90 % of the sites in the metronidazole group versus 64 % in the positive-control group had a decrease in the percentage of spirochetes ( P less than 0.05 ) . We conclude that systemic metronidazole given 250 mg tid for 7 days in conjunction with debridement of the tooth surfaces can significantly reduce the need for periodontal surgery compared to the st and ard regimen which included only debridement BACKGROUND AND OBJECTIVE The periodontal region is a source of gram-negative bacterial infection . The pathogens involved have recently also been demonstrated in atheromatous plaques . They may increase the risk of myocardial infa rct ion . In this study a strategy for eradicating periodontal bacteria and thus healing in patients with periodontal pockets and advanced destruction of alveolar bone was examined . PATIENTS AND METHODS Initial periodontal status was documented in 36 patients with periodontitis ( 24 women , 12 men ) who were then r and omly assigned to one of three groups . Those in two of the groups were given either metronidazole or doxycycline orally as adjuvant treatment , while the third group received no antibiotics . Patients in all groups were treated according to a two-step procedure . In step 1 , extensive supra- and subgingival plaques and concrements were removed . In step 2 , root debridement and /or closed curettage of all pockets was undertaken in one visit , and the antibiotic given to the patients in groups 1 and 2 . Results were assessed 3 weeks after the first step and 6 months , 2 and 4 years after step 2 . RESULTS The initial examination at 3 weeks revealed significant changes in all three groups with regard to the incidence of plaque and sulcus bleeding , but not regarding probing depth and attachment level . However , there were significant changes in probing depth and attachment level in all groups after step 2 . Periodontal attachment was significantly improved at 2 and 4 years in the patients on metronidazole , but not those on doxycycline or no antibiotics . The greatest decrease in bleeding tendency was recorded in the metronidazole group . This group also had the greatest gain of new alveolar bone compared with the other two groups . Complete eradication of Porphyromonas gingivalis and Actinobacillus ( Hemophilus ) actinomycetemcomitans , important pathogenic bacteria that may have an atherogenic action , was obtained only in patients on metronidazole . CONCLUSION The tissue-sparing two-step procedure brought about good clinical and radiological results , which can be significantly bettered by the addition of metronidazole , achieving eradication of pathogens involved in periodontal disease AIMS The objective of this study was to investigate the effect of the systemic administration of metronidazole and amoxicillin as an adjunct to initial periodontal therapy in patients with moderate to severe chronic periodontitis . METHODS AND MATERIAL S This r and omized , double blind , placebo controlled parallel study involved 50 adult patients with untreated periodontitis who were r and omly assigned to receive either a full-mouth scaling and root planing along with systemic metronidazole and amoxicillin ( T group ) or scaling and root planing with a placebo ( P group ) . Clinical measurements including probing depth ( PD ) , clinical attachment levels ( CAL ) , Plaque Index ( PI ) , and Bleeding Index ( BI ) were recorded at baseline and six to eight weeks after therapy . The deepest pocket was selected and sample s for microbiological testing were taken . Patients received coded study medications of either 500 mg amoxicillin in combination with 250 mg metronidazole or an identical placebo every eight hours for seven days following scaling and root planing . RESULTS There was a significant change in PD ( P=0.0001 ) , CAL ( P=0.00001 ) , PI ( P<0.05 ) , and BI ( P<0.05 ) in the T group compared to the placebo group after therapy . Parallel to the clinical changes , treatment significantly reduced the number of Actinobacillus actinomycetemcomitans ( Aa ) , Porphyromonas gingivalis ( Pg ) , and P. intermedia ( Pi ) compared with baseline in the T group ( P=0.003 , 0.021 and 0.0001 , respectively ) . However , in the P group only the Pi colony count was reduced significantly ( P=0.0001 ) . After therapy , there was a significant difference between the T and P groups in the number of patients negative for Aa , Pg , and Pi ( Pv = 0.033 ) . CONCLUSIONS The significant differences between treatment and placebo groups are in line with other studies and support the considerable adjunctive benefits of the combination of amoxicillin and metronidazole in the treatment of chronic periodontitis BACKGROUND AND AIM Several studies have reported adjunctive benefits to scaling and root planing ( SRP ) of systemic amoxycillin and metronidazole in the treatment of periodontal diseases . To date no comparisons have been made of these antimicrobials alone or in combination . The aim of this study was to compare the adjunctive benefits to SRP of amoxycillin and metronidazole alone and combined . METHODS 66 subjects < 46 years of age with advanced chronic periodontal disease participated in this r and omised , double blind , 4 parallel treatment group design ed study . All subjects received quadrant SRP and then were prescribed amoxycillin capsules ( 250 mg ) and metronidazole tablets ( 200 mg ) ( AM ) or lactate capsules and metronidazole ( PM ) or amoxycillin and calcium lactate tablets ( AP ) or lactate and calcium lactate ( PP ) . All medication was 3 of each per day for 7 days . Subgingival plaque sample s were obtained and probing depth ( PD ) , loss of attachment ( LOA ) , bleeding on probing ( BOP ) , suppuration ( SUPP ) and plaque ( DEP ) were recorded pre-treatment , 1 , 3 and 6 months post-treatment . RESULTS Final group sizes were : AM=15 , PM=16 , AP=16 and PP=15 . PD improved in all groups . Treatment effects were highly significantly different and always greatest in the AM and least in the PP groups . Benefits of PM and AP over PP were also noted . LOA improved in all groups and showed the same highly significant treatment differences , again favouring AM . BOP improved in all groups , particularly in AM compared to the other groups . SUPP improved in all groups and was virtually eradicated in AM with differences among treatments highly significant . DEP changed little in any group and there were no significant differences among groups . Microbiological data showed significant differences in favour of AM compared to PP and PM for total aerobes and anaerobes at 1 month . P. intermedia counts were always lower in active groups compared to PP and reached significance for AM and AP at 1 month and AM and PM at 3 months . CONCLUSION The significant differences among treatment groups and the overall trend in the data , in line with other studies , support the considerable adjunctive benefits to SRP of amoxycillin and metronidazole combined in the treatment of advanced chronic periodontal disease Considerable data have accumulated which suggest that some or most forms of periodontal disease are specific , albeit chronic , bacteriological infections ( 1 , 2 ) . In most instances the plaque flora removed from infiamed sites are dominated by anaerobic organisms such as spi-rochetes , bacteroides and eubacterium species ( 1^ ) . In some instances , the microaerophilic organism Actinobacil-lus actinom Output:

Conclusion With the performed statistical approach , a clear benefit in terms of an enhanced chance for pocket closure by co-administration of the combination of amoxicillin and metronidazole as an adjunct to non-surgical mechanical periodontal therapy has been shown . However , data calculation failed to show a benefit regarding the possible avoidance of surgical interventions

MS214140

***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: It is well established that endothelial dysfunction is present in coronary artery disease ( CAD ) , although few studies have determined the effect of training on peripheral conduit vessel function in patients with CAD . A r and omized , crossover design determined the effect of 8 wk of predominantly lower limb , combined aerobic and resistance training , in 10 patients with treated CAD . Endothelium-dependent dilation of the brachial artery was determined , by using high-resolution vascular ultrasonography , from flow-mediated vasodilation ( FMD ) after ischemia . Endothelium-independent vasodilation was measured after administration of glyceryl trinitrate ( GTN ) . Baseline function was compared with that of 10 control subjects . Compared with matched healthy control subjects , FMD and GTN responses were significantly impaired in the untrained CAD patients [ 3.0 + /- 0.8 ( SE ) vs. 5.8 + /- 0.8 % and 14.5 + /- 1.9 vs. 20.4 + /- 1.5 % , respectively ; both P < 0.05 ] . Training significantly improved FMD in the CAD patients ( from 3.0 + /- 0.8 to 5.7 + /- 1.1 % ; P < 0.05 ) but not responsiveness to GTN ( 14.5 + /- 1.9 vs. 12.1 + /- 1.4 % ; P = not significant ) . Exercise training improves endothelium-dependent conduit vessel dilation in subjects with CAD , and the effect , evident in the brachial artery , appears to be generalized rather than limited to vessels of exercising muscle beds . These results provide evidence for the benefit of exercise training , as an adjunct to routine therapy , in patients with a history of CAD The aim of this study was to investigate the effects of very high intensity sprint interval training ( SIT ) on metabolic and vascular risk factors in overweight/obese sedentary men . Ten men ( age , 32.1 ± 8.7 years ; body mass index , 31.0 ± 3.7 kg m(-2 ) ) participated . After baseline metabolic , anthropometric , and fitness measurements , participants completed a 2-week SIT intervention , comprising 6 sessions of 4 to 6 repeats of 30-second Wingate anaerobic sprints on an electromagnetically braked cycle ergometer , with 4.5-minute recovery between each repetition . Metabolic , anthropometric , and fitness assessment s were repeated post-intervention . Both maximal oxygen uptake ( 2.98 ± 0.15 vs 3.23 ± 0.14 L min(-1 ) , P = .013 ) and mean Wingate power ( 579 ± 24 vs 600 ± 19 W , P = .040 ) significantly increased after 2 weeks of SIT . Insulin sensitivity index ( 5.35 ± 0.72 vs 4.34 ± 0.72 , P = .027 ) and resting fat oxidation rate in the fasted state ( 0.13 ± 0.01 vs 0.11 ± 0.01 g min(-1 ) , P = .019 ) were significantly higher and systolic blood pressure ( 121 ± 3 vs 127 ± 3 mm Hg , P = .020 ) and resting carbohydrate oxidation in the fasted state ( 0.03 ± 0.01 vs 0.08 ± 0.02 g min(-1 ) , P = .037 ) were significantly lower 24 hours post-intervention compared with baseline , but these changes were no longer significant 72 hours post-intervention . Significant decreases in waist ( 98.9 ± 3.1 vs 101.3 ± 2.7 cm , P = .004 ) and hip ( 109.8 ± 2.2 vs 110.9 ± 2.2 cm , P = .017 ) circumferences compared with baseline were also observed after the intervention . Thus , 2 weeks of SIT substantially improved a number of metabolic and vascular risk factors in overweight/obese sedentary men , highlighting the potential for this to provide an alternative exercise model for the improvement of vascular and metabolic health in this population Aerobic exercise training combined with resistance training ( RT ) might prevent the deterioration of vascular function . However , how aerobic exercise performed before or after a bout of RT affects vascular function is unknown . The present study investigates the effect of aerobic exercise before and after RT on vascular function . Thirty-three young , healthy subjects were r and omly assigned to groups that ran before RT ( BRT : 4 male , 7 female ) , ran after RT ( ART : 4 male , 7 female ) , or remained sedentary ( SED : 3 male , 8 female ) . The BRT and ART groups performed RT at 80 % of one repetition maximum and ran at 60 % of the targeted heart rate twice each week for 8 wk . Both brachial-ankle pulse wave velocity ( baPWV ) and flow-mediated dilation ( FMD ) after combined training in the BRT group did not change from baseline . In contrast , baPWV after combined training in the ART group reduced from baseline ( from 1,025 + /- 43 to 910 + /- 33 cm/s , P < 0.01 ) . Moreover , brachial artery FMD after combined training in the ART group increased from baseline ( from 7.3 + /- 0.8 to 9.6 + /- 0.8 % , P < 0.01 ) . Brachial artery diameter , mean blood velocity , and blood flow in the BRT and ART groups after combined training increased from baseline ( P < 0.05 , P < 0.01 , and P < 0.001 , respectively ) . These values returned to the baseline during the detraining period . These values did not change in the SED group . These results suggest that although vascular function is not improved by aerobic exercise before RT , performing aerobic exercise thereafter can prevent the deteriorating of vascular function Background — Exercise training reduces the symptoms of chronic heart failure . Which exercise intensity yields maximal beneficial adaptations is controversial . Furthermore , the incidence of chronic heart failure increases with advanced age ; it has been reported that 88 % and 49 % of patients with a first diagnosis of chronic heart failure are > 65 and > 80 years old , respectively . Despite this , most previous studies have excluded patients with an age > 70 years . Our objective was to compare training programs with moderate versus high exercise intensity with regard to variables associated with cardiovascular function and prognosis in patients with postinfa rct ion heart failure . Methods and Results — Twenty-seven patients with stable postinfa rct ion heart failure who were undergoing optimal medical treatment , including & bgr;-blockers and angiotensin-converting enzyme inhibitors ( aged 75.5±11.1 years ; left ventricular [ LV ] ejection fraction 29 % ; & OV0312;o2peak 13 mL · kg−1 · min−1 ) were r and omized to either moderate continuous training ( 70 % of highest measured heart rate , ie , peak heart rate ) or aerobic interval training ( 95 % of peak heart rate ) 3 times per week for 12 weeks or to a control group that received st and ard advice regarding physical activity . & OV0312;o2peak increased more with aerobic interval training than moderate continuous training ( 46 % versus 14 % , P<0.001 ) and was associated with reverse LV remodeling . LV end-diastolic and end-systolic volumes declined with aerobic interval training only , by 18 % and 25 % , respectively ; LV ejection fraction increased 35 % , and pro-brain natriuretic peptide decreased 40 % . Improvement in brachial artery flow-mediated dilation ( endothelial function ) was greater with aerobic interval training , and mitochondrial function in lateral vastus muscle increased with aerobic interval training only . The MacNew global score for quality of life in cardiovascular disease increased in both exercise groups . No changes occurred in the control group . Conclusions — Exercise intensity was an important factor for reversing LV remodeling and improving aerobic capacity , endothelial function , and quality of life in patients with postinfa rct ion heart failure . These findings may have important implication s for exercise training in rehabilitation programs and future studies Although high-intensity resistance training increases central arterial stiffness , moderate-intensity resistance training does not . However , the effects of low-intensity resistance training on arterial stiffness are unknown . The aim of this study was to investigate the effect of low-intensity resistance training with short inter-set rest period ( LSR ) on arterial stiffness . Twenty-six young healthy subjects were r and omly assigned to training ( 10 males , 3 females ) and control groups ( 9 males , 4 females ) . The subjects performed LSR twice a week at 50 % of one repetition maximum for 10 weeks . Training consisted of five sets of ten repetitions with an inter-set rest period of 30 s. Changes in brachial-ankle pulse wave velocity ( baPWV ) and brachial flow-mediated dilation ( FMD ) were assessed before and after the intervention period . After the intervention period , one repetition maximum strength increased ( by 9–38 % , P < 0.05 to < 0.001 ; increases varied among the exercise types ) , baPWV decreased ( from 1,093 ± 148 to 1,020 ± 128 cm/s , P < 0.05 ) , and brachial FMD increased ( from 9.7 ± 1.3 to 11.8 ± 1.9 % , P < 0.05 ) . These values did not change in the control group . These results suggest that LSR reduced arterial stiffness and improved vascular endothelial function OBJECTIVES The aim of this study was to assess the efficacy of exercise and antidepressant medication in reducing depressive symptoms and improving cardiovascular biomarkers in depressed patients with coronary heart disease . BACKGROUND Although there is good evidence that clinical depression is associated with poor prognosis , optimal therapeutic strategies are currently not well defined . METHODS One hundred one out patients with coronary heart disease and elevated depressive symptoms underwent assessment of depression , including a psychiatric interview and the Hamilton Rating Scale for Depression . Participants were r and omized to 4 months of aerobic exercise ( 3 times/week ) , sertraline ( 50 - 200 mg/day ) , or placebo . Additional assessment s of cardiovascular biomarkers included measures of heart rate variability , endothelial function , baroreflex sensitivity , inflammation , and platelet function . RESULTS After 16 weeks , all groups showed improvement on Hamilton Rating Scale for Depression scores . Participants in both the aerobic exercise ( mean -7.5 ; 95 % confidence interval : -9.8 to -5.0 ) and sertraline ( mean -6.1 ; 95 % confidence interval : -8.4 to -3.9 ) groups achieved larger reductions in depressive symptoms compared with those receiving placebo ( mean -4.5 ; 95 % confidence interval : -7.6 to -1.5 ; p = 0.034 ) ; exercise and sertraline were equally effective at reducing depressive symptoms ( p = 0.607 ) . Exercise and medication tended to result in greater improvements in heart rate variability compared with placebo ( p = 0.052 ) ; exercise tended to result in greater improvements in heart rate variability compared with sertraline ( p = 0.093 ) . CONCLUSIONS Both exercise and sertraline result ed in greater reductions in depressive symptoms compared to placebo in patients with coronary heart disease . Evidence that active treatments may also improve cardiovascular biomarkers suggests that they may have a beneficial effect on clinical outcomes as well as on quality of life . ( Exercise to Treat Depression in Individuals With Coronary Heart Disease ; NCT00302068 ) Objectives The aim of this study was to examine the effect of three different doses of aerobic exercise training ( corresponding to approximately 50 % , 100 % and 150 % of the National Institutes of Health consensus guidelines ) on endothelial function in sedentary obese postmenopausal women with elevated blood pressure . Aerobic exercise training improves endothelial function in individuals with cardiovascular risk ; however , it is unknown whether these adaptations occur in a dose-dependent manner . Methods Obese postmenopausal women ( n=155 ) with elevated blood pressure ( systolic blood pressure between 120 and 159.0 mm Hg ) were r and omly assigned to one of four groups : 4 , 8 or 12 kilocalories per kilogram of energy expenditure per week ( kcal/kg/week ) or a non-exercise control group for 6 months . Endothelial function was assessed via flow-mediated dilation ( FMD ) at baseline and post-intervention . Results After exercise training , there was a similar improvement ( 1.02–1.5 % ) in FMD in all three exercise groups ( p<0.05 ) compared with control ( –0.5 % ) . Change in FMD after exercise training was significantly correlated with FMD at baseline ( r= –0.35 , p<0.001 ) . Post hoc analyses found a significant improvement in FMD in exercisers ( all exercise groups combined ) with endothelial dysfunction ( FMD < 5.5 % Output:

Conclusions All exercise modalities improve EF significantly and there was a significant , positive relationship between aerobic exercise intensity and EF . Greater frequency , rather than intensity , of resistance exercise training enhanced EF

MS214141

***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: Severe oral mucositis is a major cause of morbidity following allogeneic hematopoietic stem cell transplantation ( AHSCT ) . Cryotherapy , that is , the application of ice chips on the mucosa of the oral cavity during the administration of antineoplastic agents , may reduce the incidence and severity of chemotherapy-related oral mucositis . In this multicenter r and omized study , we addressed whether cryotherapy during MTX administration is effective in the prevention of severe oral mucositis in patients undergoing myeloablative AHSCT . One hundred and thirty patients undergoing myeloablative AHSCT and MTX-containing GVHD prophylaxis were enrolled and r and omized to receive or not receive cryotherapy during MTX administration . The incidence of severe ( grade 3–4 ) oral mucositis , the primary end point of the study , was comparable in patients receiving or not cryotherapy . Moreover , no difference was observed in the incidence of oral mucositis grade 2–4 and the duration of oral mucositis grade 3–4 or 2–4 , or in the kinetics of mucositis over time . In univariate and multivariate analysis , severe oral mucositis correlated with TBI in the conditioning regimen and lack of folinic acid rescue following MTX administration . Thus , cryotherapy during MTX administration does not reduce severe oral mucositis in patients undergoing myeloablative allogeneic HSCT . Future studies will assess cryotherapy before allogeneic HSCT Purpose : Edatrexate ( 10-Edam ) is a methotrexate analog with improved intracellular transport , polyglutamation , and antitumor activity compared to the parent compound . Edatrexate shows schedule-dependent synergism with platinum compounds in pre clinical studies . We performed a phase I trial to determine toxicities and establish the maximum tolerated dose ( MTD ) of edatrexate in combination with carboplatin . Based on the short initial plasma half-life of edatrexate , prophylactic ice chip cryotherapy was used to reduce the severity of mucositis . Patients and methods : Forty-six chemotherapy-naive patients with advanced solid tumors were treated . Edatrexate was given weekly for 5 doses ( 50 % on day 8) , and then every other week , followed by carboplatin at a fixed dose of 350 mg/m2 on day 1 and then every 4 weeks for 8 cycles . Edatrexate dose was increased at increments of 10 mg/m2/dose level beginning at 60 mg/m2/week ( range 60–120 mg/m2 ) . Results : All patients were assessable for toxicity and response analysis . The median number of cycles administered per patients was 4 . This combination chemotherapy regimen was well tolerated . Using ice chip cryotherapy , no grade IV mucositis was observed . Grade III mucositis occurred in only 7/46 pts and was not dose-related . Protocol -defined dose-limiting toxicity occurred at a edatrexate dose level of 120 mg/m2 , yielding an MTD of 110 mg/m2 . Responding tumor types included non-small cell and small lung cancer , head and neck cancer , and bladder cancer . Conclusions : 1 ) This phase I study demonstrated the safety and tolerability of this edatrexate and carboplatin combination . 2 ) Dose-limiting mucositis did not occur allowing escalation of edatrexate dose above levels previously achieved with this edatrexate dose schedule . This was most likely a result of prophylactic ice chip cryotherapy . 3 ) An edatrexate dose of 110 mg/m2 with ice chip cryotherapy is recommended for Phase II trials of this combination AIM AND OBJECTIVE To investigate if oral cryotherapy during myeloablative therapy may influence frequency and severity of mucositis , nutritional status and infection rate after bone marrow transplantation . BACKGROUND Patients treated with intensive myeloablative treatment before bone marrow transplantation are all at risk to develop mucositis . Oral mucositis causes severe pain and oral dysfunction , which can contribute to local and systemic infections and bleeding ; it may even interrupt cancer therapy . Oral mucositis also decreases the oral food intake , which increases the risk for malnutrition and infection . Reduced food intake , loss of fat and muscles , alterations in energy and substrate metabolism leads to malnutrition . DESIGN A r and omised controlled trial with a r and om assignment to experimental or control group . METHOD A stratified r and omisation was used with regard to the type of transplantation . Mucositis was measured on WHO mucositis scale . Number of days of total parenteral nutrition , infection rate , weight , albumin levels and days at hospital was compared . RESULTS There were significantly fewer patients in the experimental group with mucositis grade 3 - 4 than in the control group and significantly lower number of days in the hospital ( allogeneic patients ) . Less total parenteral nutrition was needed in the experimental group in both setting s , and the S-albumin level was significantly better preserved . No significant difference could be found with regard to infection rate . CONCLUSION Oral cryotherapy reduced mucositis , number of hospital days , the need for total parenteral nutrition and result ed in a better nutritional status . RELEVANCE TO CLINICAL PRACTICE Nurses caring for patients treated with myeloablative therapy should place high priority to prevent oral mucositis and hereby reduce its side effects AIMS AND OBJECTIVES The study aim ed to compare the use of plain ice , flavoured ice and st and ard care , to evaluate the effect on mucositis and to determine patients ' perceptions of the two forms of oral cryotherapy . BACKGROUND Despite evidence that oral cryotherapy is useful in preventing mucositis in patients receiving 5-fluorouracil , concerns have been expressed about its clinical utility , due to potential side effects and negative perceptions . DESIGN A r and omized , controlled , crossover trial was conducted in the outpatient chemotherapy department of an acute care teaching hospital in Perth , Western Australia . Patients were r and omized to receive each of three interventions across three cycles of chemotherapy : st and ard care alone ; st and ard care plus plain ice ; and st and ard care plus flavoured ice . METHODS Oral mucositis was assessed by nurses prior to each of the three chemotherapy cycles and 15 days after each intervention . Two assessment tools were used , the Oral Assessment Guide , and the Western Consortium Cancer Nursing Research Scale . Participants completed a question naire to determine their comfort and satisfaction with oral cryotherapy , as well as factors affecting compliance . RESULTS Findings from 67 patients revealed that when participants used st and ard care alone , they were significantly more likely to experience symptoms of mucositis than when they used either plain or flavoured ice . Odds ratios were at least threefold higher for st and ard care alone , varying according to the instrument used . The two main concerns reported were the taste of flavoured ice and the time required to complete the cryotherapy interventions . Side effects such as nausea , sensitivity and headache were reported more frequently for flavoured ice ( n = 11 ) compared with plain ice ( n = 5 ) and st and ard care ( n = 1 ) . CONCLUSIONS Both forms of oral cryotherapy were effective in reducing the severity of oral mucositis after chemotherapy and were more effective than st and ard care alone . Flavoured ice was associated with the highest frequency of side effects . RELEVANCE TO CLINICAL PRACTICE The benefits of cryotherapy appear to outweigh the problems in this sample of patients . The intervention should be tailored to individual patients , based on preferences for plain versus flavoured ice and small chips vs. larger blocks . Unsweetened frozen fruit juices should be evaluated . Time constraints could be addressed by providing transportable containers of ice Recently , a r and omised study demonstrated the utility of oral cooling ( cryotherapy ) in the prevention of 5-fluorouracil (5FU)-induced stomatitis . In order to verify these results a confirmatory study , using identical treatment regimen , was initiated . 84 patients treated with a 5-FU-containing regimen were r and omised to a control arm or to receive oral cryotherapy . End point evaluation was obtained by a global assessment of the physician 's judgement and patients ' description of mucositis severity grade d 0 - 4 . Mucositis was significantly reduced by cryotherapy considering both the first cycle of therapy ( the mean toxicity score for cryotherapy was 0.59 and it was 1.1 for the control group , P < or = 0.05 ) and all the chemotherapeutic courses ( the mean toxicity score for cryotherapy was 0.36 when it was 0.69 for the control group , P < or = 0.05 ) . In conclusion , the present study confirms that cryotherapy can decrease 5FU-induced stomatitis and should be recommended for patients receiving bolus 5FU-containing regimens Mucositis is a significant dose-limiting toxicity associated with fluorouracil ( 5FU ) , particularly when it is combined with leucovorin . We hypothesized that oral cryotherapy would cause local vasoconstriction and would temporarily decrease blood flow to the oral mucous membranes . If cryotherapy were used during the time of peak serum 5FU levels , then the oral mucous membranes would have less exposure to 5FU and thus develop less mucositis . To test this hypothesis , 95 patients scheduled to receive their first cycle of 5FU plus leucovorin were r and omized to have oral cryotherapy at the time of chemotherapy administration or to serve as a control group . Subsequent mucositis was significantly reduced in the group assigned to receive cryotherapy as judged by the attending physicians ( P = .0002 ) and by the patients themselves ( P = .0001 ) . We now routinely recommend this cryotherapy procedure for our patients receiving daily bolus 5FU plus leucovorin Stomatitis is a common adverse effect of intravenously infused 5-fluorouracil ( 5FU ) . Although there are encouraging studies about the preventive role of oral cryotherapy in stomatitis induced by intravenous administration of 5FU , this simple and cost-effective method is not part of clinical practice . This prospect i ve r and omized study investigates whether oral cryotherapy alleviates 5FU-induced stomatitis . Thirty six patients , included in the cryotherapy group , were instructed to hold ice cubes in their oral cavity , shortly before , during and shortly after the infusion of 5FU . Both mean physician and patient- grade d stomatitis of our cryotherapy group were compared with those of a control group ( 40 patients ) and were found significantly reduced for all three chemotherapy cycles . The percentage of patients who were free from oral toxicity was significantly higher in the cryotherapy group in all three chemotherapy cycles , as judged both by patients and physicians . The results of this study encourage the use of cryotherapy in patients receiving 5FU in alleviating stomatitis by using a side-effect-free , easy to perform and inexpensive measure , which does not interfere with the efficacy of antineoplastic agents Mucosal toxicity is an incapacitating complication of intensive chemo-radiotherapy for children with malignant disorders , and is physically and psychologically distressful . It is therefore important to minimize mucosal toxicity in those patients . In this report , the effects of the combined prophylaxis of oral cooling ( cryotherapy ) and administration of propantheline , an anticholinergic drug , were studied in patients ( aged 2 - 16 year ) with acute leukemias or solid tumors , who underwent myeloablative chemo-radiotherapy and autologous peripheral blood stem cell rescue from 1993 to 1997 . Patients were pretreated with the combined prophylaxis ( n = 12 ) or single prophylaxis ( n = 5 ) , or left untreated ( n = 7 ) . The combined prophylaxis significantly reduced the severe mucositis ( combined , 8.3 % ; single , 20.0 % ; and untreated , 42.9 % ) and severe diarrhea ( combined , 16.7 % ; single , 60.0 % ; and untreated , 57.1 % ) . Moreover , the combined prophylaxis tended to shorten the periods of febrile episodes defined as temperature > 38 degrees C ( combined , 3.8 days ; single , 4.6 days ; and untreated , 5.6 days ) . Therefore , the combination of propantheline and oral cryotherapy may be feasible and effective for reduction of mucosal toxicity in patients with malignancy who undergo high-dose chemotherapy Background . The authors previously reported that 30 minutes of oral cryotherapy inhibits 5‐fluorouracil (5‐FU)‐induced stomatitis . The current trial was design ed to determine whether a longer duration of cryotherapy would provide additional protection Introduction Mucositis is a major complication in myeloablative therapy , which often necessitates advanced pharmacological pain treatment , including i.v . opioids . Attempts to prevent oral mucositis have included oral cryotherapy , which has been shown to reduce mucositis , but there is a lack of knowledge concerning the effect of oral cryotherapy on opioid use by reducing the mucositis for patients treated with myeloablative therapy before bone marrow transplantation ( BMT ) . Aim The aim of the present study was to evaluate if oral cryotherapy could delay or alleviate the development of mucositis and thereby reduce the number of days with i.v . opioids among patients who receive Output:

The recommendation for the use of oral cryotherapy to prevent oral mucositis in patients receiving bolus fluorouracil ( 5-FU ) was maintained , in agreement with the 2007 guidelines . Conclusions The evidence continues to support the use of oral cryotherapy for prevention of oral mucositis in patients receiving bolus 5-FU chemotherapy or high-dose melphalan . This intervention is consistent with the MASCC/ISOO guidelines published in 2007 .

MS214142

***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: Asthma patients pose special problems as far as the medical supervision , danger of symptoms and the course of the disease are concerned . Some 90 asthma patients were registered for the treatment in the Heidelberg Medical Clinic . 31 patients who were interested in taking part were r and omized into 3 groups : two treatment group consisted of the exchange of information , discussion sessions on the illness as well as ' autogenic training ' or ' functional relaxation ' . The third group was the control group . Before and after treatment the patients were su bmi tted to a thorough examination both of lungs and other internal organs as well as from the psychodiagnostical point of view . The average age of the patients was 43.5 years and the average duration of illness 16.8 years . Nevertheless , the treatment group 's sympathomimetics use was significantly reduced by 1 year of treatment ( p less than 0.05 ) ; the use of steroids decreased as well . The number of visits of the general practitioner also decreased . These results support the conclusion that psychosomatic group therapy can make an important contribution to the treatment of asthma patients . Body therapy practised in ' autogenic training ' and ' functional relaxation ' seems to be another important healing factor for the treatment in addition to the discussion sessions and the exchange of information Stress , unpleasant emotions and autonomic imbalance may play a main role in precipitating asthmatic attacks . In this study two homogeneous groups of asthmatic patients ( N = 24 ) are treated over an eight-month period . The experimental group was treated with autogenic therapy and the control group with supportive group psychotherapy . Respiratory function parameters measured were Forced Vital Capacity ( FVC ) , Forced Expiratory Volume in the first sec ( FEV1 ) , Forced Expiratory Flow between 25 % and 75 % of the FVC ( FEF25 - 75 % ) , and Mesoexpiratory Flow ( MEF50 % ) . The group under Autogenic Therapy obtained a relevant clinical improvement ( > 15 % of pretreatment values ) in respiratory function . No significant changes were observed in the control group . These results suggest that autogenic therapy could be an effective adjunctive treatment in bronchial asthma One hundred six asthmatic subjects were medically prestabilized , then assigned to eight sessions of progressive relaxation , music , or a waiting-list . Seventy-two subjects completed treatment , of which 37 were evaluated in the laboratory with measures of forced expiratory flow . Relaxation-group subjects reported feeling the most deeply relaxed and produced the greatest improvement in forced expiratory flow during the last presession assessment period . All groups evidence d decreases in asthma symptoms . All groups showed decreases in pulmonary function immediately after relaxation sessions . None of the changes in pulmonary function reached levels that are accepted in drug trials to be of clinical significance , and the therapeutic changes occurred only in the situation where training was rendered . Listening to music produced greater decreases in peaks of tension than progressive relaxation , and it produced greater compliance with relaxation practice , but it did not produce any specific therapeutic effects on asthma BACKGROUND High levels of stress have been shown to predict the onset of asthma in children genetically at risk , and to correlate with higher asthma morbidity . Our study set out to examine whether stressful experiences actually provoke new exacerbations in children who already have asthma . METHODS A group of child patients with verified chronic asthma were prospect ively followed up for 18 months . We used continuous monitoring of asthma by the use of diaries and daily peak-flow values , accompanied by repeated interview assessment s of life events and long-term psychosocial experiences . The key measures included asthma exacerbations , severely negative life events , and chronic stressors . FINDINGS Severe events , both on their own and in conjunction with high chronic stress , significantly increased the risk of new asthma attacks . The effect of severe events without accompanying chronic stress involved a small delay ; they had no effect within the first 2 weeks , but significantly increased the risk in the subsequent 4 weeks ( odds ratio 1.71 [ 95 % CI 1.04 - 2.82 ] , p < or = 0.05 for weeks 2 - 4 and 2.17 [ 1.32 - 3.57 ] , p < or = 0.01 for weeks 4 - 6 ) . When severe events occurred against the backdrop of high chronic stress , the risk increased sharply and almost immediately within the first fortnight ( 2.98 [ 1.20 - 7.38 ] , p < or = 0.05 ) . The overall attack frequency was affected by several factors , some related to asthma and some to child characteristics . Female sex , higher baseline illness severity , three or more attacks within 6 months , autumn to winter season , and parental smoking were all related to increased risk of new exacerbations ; social class and chronic stress were not . INTERPRETATION Severely negative life events increase the risk of children 's asthma attacks over the coming few weeks . This risk is magnified and brought forward in time if the child 's life situation is also characterised by multiple chronic stressors Abstract To assess the role of the autonomic nervous system in the bronchospasm which occurs in asthmatic children following exercise , β-adrenergic , α-adrenergic , or cholinergic blockade was induced by the intravenous injection of propranolol , phentolamine , or atropine , respectively , with saline as a control . Treatments were given by r and om assignment once to each of 10 asthmatic children on each of four successive afternoons , with each child acting as his own control . Measurement of peak expiratory flow rates ( PEFR ) before injections , 15 minutes later before st and ard treadmill exercise , and 10 minutes after completion of 8 minutes of exercise disclosed a significant decrease in PEFR following injection with propranolol only . Pulse rate alterations were consistent with the various kinds of blockade sought . None of the treatments affected the decrease in PEFR induced by exercise . It seems unlikely , therefore , that exercise-induced bronchospasm is mediated in major fashion by the autonomic nervous system Abstract Twelve patients with chronic bronchial asthma were matched in pairs and r and omly assigned to two treatment groups , one group received mental and muscular relaxation , the second group received muscular relaxation alone . Treatment consisted of 4 weekly treatment sessions . Pre , post and follow-up phases each consisted of 3 weekly sessions . Respiratory function was measured by the forced expiratory volume in 1 second ( FEV 1 ) . Two self-report inventories were used to measure change in the symptoms and signs of the patient 's asthma . Following factor analysis , 3 factors were used — Psychological , Physical and Bronchoconstriction . Results showed that for each of these 3 factors and for FEV 1 , there was no overall mean significant difference between results in either treatment group . In addition , patients showed no significant trend of improvement in respiratory function . No significant difference was shown between respiratory function recorded before and after relaxation treatment in each of the individual treatment sessions . There was a moderate correlation between objective recordings and the patient 's subjective assessment of asthma severity Thirty-two children with asthma ( 16 4- to 8-year-olds and 16 9- to 14-year-olds ) were r and omly assigned to receive either massage therapy or relaxation therapy . The children 's parents were taught to provide one therapy or the other for 20 minutes before bedtime each night for 30 days . The younger children who received massage therapy showed an immediate decrease in behavioral anxiety and cortisol levels after massage . Also , their attitude toward asthma and their peak air flow and other pulmonary functions improved over the course of the study . The older children who received massage therapy reported lower anxiety after the massage . Their attitude toward asthma also improved over the study , but only one measure of pulmonary function ( forced expiratory flow 25 % to 75 % ) improved . The reason for the smaller therapeutic benefit in the older children is unknown ; however , it appears that daily massage improves airway caliber and control of asthma Output:

There is a lack of evidence for the efficacy of relaxation therapies in the management of asthma . There is some evidence that muscular relaxation improves lung function of patients with asthma but no evidence for any other relaxation technique

MS214143

***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: Post-operative complications after total hip or knee replacement can delay recovery , prolong hospitalisation , increase rates of re-admission and , in the most severe cases , lead to long-term disability or even death . In this analysis of pooled data from four large , r and omised , phase III clinical trials that compared the oral , direct Factor Xa inhibitor rivaroxaban with subcutaneous enoxaparin for the prevention of venous thromboembolism after total hip or knee replacement ( n = 12,729 ) , the incidence of complications , including bleeding and adverse events related to surgery ( such as wound infection , wound dehiscence and haemarthrosis ) are reported . Interventions and procedures relating to surgery are also compared between the groups . Bleeding events , including excessive wound haematoma and surgical-site bleeding , occurred at similar rates in the rivaroxaban and enoxaparin groups . Over the total study duration , adverse surgical events occurred at a similar rate in the rivaroxaban group compared with the enoxaparin group after total knee replacement ( 2.26 % vs. 2.69 % , respectively ) and total hip replacement ( 1.48 % vs. 1.65 % , respectively ) . Blood loss , wound drainage and transfusion requirements were also similar between the two groups . This analysis shows that the incidence of adverse surgical events with rivaroxaban was similar to enoxaparin Rivaroxaban has been recommended for routine use as a thromboprophylactic agent in patients undergoing lower-limb arthroplasty . However , trials supporting its use have not fully evaluated the risks of wound complications . This study of 1048 total hip/knee replacements records the rates of return to theatre and infection before and after the change from a low molecular weight heparin ( tinzaparin ) to rivaroxaban as the agent of chemical thromboprophylaxis in patients undergoing lower-limb arthroplasty . During a period of 13 months , 489 consecutive patients undergoing lower-limb arthroplasty received tinzaparin and the next 559 consecutive patients received rivaroxaban as thromboprophylaxis . Nine patients in the control ( tinzaparin ) group ( 1.8 % , 95 % confidence interval 0.9 to 3.5 ) returned to theatre with wound complications within 30 days , compared with 22 patients in the rivaroxaban group ( 3.94 % , 95 % confidence interval 2.6 to 5.9 ) . This increase was statistically significant ( p = 0.046 ) . The proportion of patients who returned to theatre and became infected remained similar ( p = 0.10 ) . Our study demonstrates the need for further r and omised controlled clinical trials to be conducted to assess the safety and efficacy of rivaroxaban in clinical practice , focusing on the surgical complications as well as the potential prevention of venous thromboembolism Background This study aim ed to assess whether the efficacy of tranexamic acid ( TXA ) would be altered when rivaroxaban or enoxaparin was used for thromboprophylaxis in primary total knee replacement ( TKR ) . It was hypothesized that the hemostatic effect of TXA would be better with the use of enoxaparin . Material / Methods A r and omized clinical trial was conducted on 194 patients undergoing primary TKR for osteoarthritis . An intravenous dose of 15 mg/kg ( TXA ) and 1 g topical TXA were used . Patients r and omly received enoxaparin or rivaroxaban prophylaxis when the drainage was less than 30 ml/h 6–8 h postoperatively . The primary endpoint was hidden blood loss ( HBL ) . Indexes of total blood loss drainage , hemoglobin drop , transfusion , range of motion ( ROM ) , HSS score , VAS pain score , knee swelling , length of hospital stay ( LOHS ) , incidence of venous thromboembolism , major/minor bleeding , and wound complications were also compared between the groups . Results More than 80 % of patients initiated anticoagulation within 6 h postoperatively . No statistically significance difference was detected in terms of HBL ( 679.0±205.6 vs. 770.5±206.1 , p=.062 ) or other bleeding index , ROM , or LOHS . The motion VAS pain score and knee swelling ( 16.7 % vs. 6.1 % , p=.021 ) were significantly lower , and HSS score at discharge was higher in the enoxaparin group . The rivaroxaban group had less asymptomatic deep venous ( 4.1 % vs. 0 % , p=.121 ) and muscular venous thrombosis ( 2.1 % vs. 9.2 % , p=.033 ) ; more ecchymosis ( 13.5 % vs. 10.2 % , p=.472 ) , and wound complications ( 13.5 % vs. 6.1 % , p=.082 ) . No episodes of transfusion , pulmonary embolism , or major bleeding occurred in either group . Conclusions More attention should be paid to the increased risk of wound complications and knee swelling associated with rivaroxaban , although the hidden blood loss was similar in both groups Purpose Venous thromboembolism is a common complication after major orthopedic surgery . When prescribing anticoagulant prophylaxis , clinicians weigh the benefits of thromboprophylaxis against bleeding risk and other adverse events . Previous benefit – risk analyses of the REgulation of Coagulation in ORthopaedic surgery to prevent Deep vein thrombosis and pulmonary embolism ( RECORD ) r and omized clinical studies of rivaroxaban versus enoxaparin after total hip ( THA ) or knee ( TKA ) arthroplasty generally used pooled THA and TKA results , counted fatal bleeding as both an efficacy and a safety event , and included the active and placebo-controlled portions of RECORD2 , which might confound benefit – risk assessment s. We conducted a post hoc analysis without these constraints to assess benefit – risk for rivaroxaban versus enoxaparin in the RECORD studies . Patients and methods Data from the safety population of the two THA and two TKA studies were pooled separately . The primary analysis compared the temporal course of event rates and rate differences between rivaroxaban and enoxaparin prophylaxis for symptomatic venous thromboembolism plus all-cause mortality ( efficacy events ) versus nonfatal major bleeding ( safety events ) . Additionally , these rates were used to derive measures of net clinical benefit , number needed to treat ( NNT ) , and number needed to harm ( NNH ) for these two end points . Results After THA or TKA , and compared with enoxaparin , rivaroxaban therapy result ed in more efficacy events prevented than safety events caused , with benefits exceeding harms early and throughout treatment and follow-up . Relative to enoxaparin , rivaroxaban treatment prevented six efficacy events per harm event caused for THA , with NNT = 262/NNH = 1,711 . For TKA , rivaroxaban treatment prevented four to five efficacy events per harm event caused , with NNT = 102/NNH = 442 . Sensitivity analysis that included surgical-site bleeding result ed in NNH = 345 for THA and NNH = 208 for TKA . Conclusion In the RECORD studies , considering death , symptomatic venous thromboembolism , and major bleeding , rivaroxaban result ed in greater benefits than harms compared with enoxaparin . When incorporating surgical-site bleeding , rivaroxaban also results in greater benefit than harm for TKA and is balanced with enoxaparin for THA OBJECTIVES To compare the main efficacy and safety endpoints of the pivotal r and omised clinical trials ( RCTs ) on venous thromboembolism ( VTE ) prevention after total hip ( THR ) or knee ( TKR ) replacement with the new oral anticoagulants ( NAs ) versus enoxaparin . METHODS A pool- analysis of 10 RCTs that included 32.144 r and omised patients was performed . Efficacy outcomes were total VTE and all-cause mortality , major VTE , and proximal DVT . Safety outcomes were major bleeding , and clinical ly relevant ( major or non-major ) bleeding . RESULTS Overall , a significant effect favouring NAs was found for the primary efficacy outcome ( RR 0.71 ; 95%CI 0.56 - 0.90 ) , major VTE ( RR 0.59 ; 95%CI 0.41 - 0.84 ) , and proximal DVT ( RR 0.51 ; 95%CI 0.35 - 0.76 ) . Compared to enoxaparin 40 mg QD , rivaroxaban showed superiority ( RR 0.50 ; 95%CI 0.34 - 0.73 ) , followed by apixaban ( RR 0.63 ; 95%CI 0.36 - 1.01 ) and dabigatran ( RR 1.02 ; 95%CI 0.86 - 1.20 ) . There was significant heterogeneity among trials and subgroups analysed for these efficacy outcomes . Major bleeding ( RR 1.04 ; 95 % CI 0.74 - 1.46 ) and clinical ly relevant bleeding ( RR 1.03 ; 95%CI 0.88 - 1.21 ) was similar with NAs or enoxaparin . Rivaroxaban showed a trend toward more major bleeding episodes than enoxaparin ( RR 1.88 ; 95%CI 0.92 - 3.82 ) and apixaban showed the lowest clinical ly relevant bleeding risk ( RR 0.81 ; 95%CI 0.64 - 1.01 ) . CONCLUSIONS Overall , NAs showed more efficacy and same safety when compared to the recommended dose of enoxaparin after THR and TKR . There are little differences in efficacy and bleeding risk among NAs and the type of prophylaxis that should be analysed further This study aim ed to compare the efficacy and safety of aspirin , rivaroxaban and low-molecular-weight heparin ( LMWH ) for post total knee arthroplasty ( TKA ) deep vein thrombosis ( DVT ) prophylaxis . Between July 2011 and July 2013 , a prospect i ve r and omized controlled trial was performed on 324 patients with osteoarthritis who underwent primary unilateral TKA . Twelve hours after the surgery , Group A was given oral rivaroxaban at a dose of 10 mg/day . Group B was given subcutaneous LMWH at a dose of 4000 AxaIU ( 0.4 ml)/day and Group C was given oral aspirin at a dose of 100 mg/day . All three groups were treated for 14 days , and all of the patients were followed for 4 weeks . The incidence of DVT , dominant/hidden blood loss , the incidence of wound complications and the incidence of subcutaneous ecchymosis in the affected extremities were compared between the three groups . The incidence of DVT was lower in Group A compared with the other two groups [ 3 ( 2.94 % ) vs. 14 ( 12.50 % ) , P = 0.029 ; 3 ( 2.94 % ) vs. 18 ( 16.36 % ) , P = 0.017 ] . However , hidden blood loss [ 1.71 ( 1.19–2.97 ) vs. 1.18 ( 0.77–2.31 ) , P = 0.009 ; 1.71 ( 1.19–2.97 ) vs. 1.30 ( 0.61–2.43 ) , P = 0.004 ] and wound complications [ 5 ( 4.90 ) vs. 3 ( 2.67 ) , P = 0.027 ; 5 ( 4.90 ) vs. 2 ( 1.82 ) , P = 0.014 ] were more common in Group A than in the other groups . There were no significant differences between Group B and Group C in the incidence of DVT [ 14 ( 12.50 % ) vs. 18 ( 16.36 % ) , P = 0.831 ] , hidden blood loss [ 1.18 ( 0.77–2.31 ) vs. 1.30 ( 0.61–2.43 ) , P = 0.327 ] or wound complications [ 3 ( 2.67 ) vs. 2 ( 1.82 ) , P = 0.209 ] . No significant differences in the incidence of limb swelling were found between the three groups [ 38 ( 37.25 % ) vs. 28 ( 25.00 % ) vs. 24 ( 21.82 % ) , P = 0.247 ] . Group A had a higher incidence of subcutaneous ecchymosis in the affected extremities than Group C [ 74 ( 72.55 % ) vs. 54 ( 49.09 % ) , P = 0.039 ] , but there were no significant differences between Groups A and B [ 74 ( 72.55 % ) vs. 62 ( 55.36 % ) , P = 0.193 ] or between Groups B and C [ 62 ( 55.36 % ) vs. 54 ( 49.09 % ) , P = Output:

In the studies analyzed , considering symptomatic venous thromboembolism , rivaroxaban result ed in higher benefits when compared to enoxaparin

MS214144

***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 primary purpose of this r and omized controlled trial ( RCT ) was to compare knee-specific outcomes ( stiffness , pain , function ) between patellar retention and resurfacing up to 10 years after primary total knee arthroplasty ( TKA ) . Secondarily , we compared re-operation rates . Methods 38 subjects with non-inflammatory arthritis were r and omized at primary TKA surgery to receive patellar resurfacing ( n = 21 ; Resurfaced group ) or to retain their native patella ( n = 17 ; Non-resurfaced group ) . Evaluations were performed preoperatively , one , five and 10 years postoperatively by an evaluator who was blinded to group allocation . Self-reported knee-specific stiffness , pain and function , the primary outcomes , were measured by the Western Ontario McMaster Osteoarthritis Index ( WOMAC ) . Revision rate was determined at each evaluation and through hospital record review . Results 30 ( 88 % ) and 23 ( 72 % ) of available subjects completed the five and 10-year review respectively . Knee-specific scores continued to improve for both groups over the 10-years , despite diminishing overall health with no significant group differences seen . All revisions occurred within five years of surgery ( three Non-resurfaced subjects ; one Resurfaced subject ) ( p = 0.31 ) . Two revisions in the Non-resurfaced group were due to persistent anterior knee pain . Conclusions We found no differences in knee-specific results between groups at 5–10 years postoperatively . The Non-resurfaced group had two revisions due to anterior knee pain similar to rates reported in other studies . Knee-specific results provide useful postoperative information and should be used in future studies comparing patellar management strategies . Clinical Trials.gov The superiority between the posterior cruciate-retaining and the posterior cruciate-substituting design s still remains controversial . We performed a prospect i ve , r and omized control study for evaluation of the superiority of these design s. This study investigated 58 knees in 29 patients with simultaneous bilateral total knee arthroplasty , in which the high-flex CR design was r and omly implanted in one knee and the high-flex PS design was implanted in the other knee . The follow-up duration averaged 5.0 years , with a minimum duration of 3 years . Postoperatively , Knee Score and pain points in Knee Score result ed in no significant differences between the 2 design s. However , postoperative arc of range of motion , patient satisfaction , and posterior knee pain at passive flexion in the PS design were significantly superior to that of the CR design Background Total knee arthroplasty with the use of a tourniquet during the entire operation has not been shown to improve the performance of the operation and may increase the risk of complications . Questions / purpose sWe asked whether the limited use of a tourniquet for cementation only would affect ( 1 ) surgical time ; ( 2 ) postoperative pain and motion of the knee ; ( 3 ) blood loss ; or ( 4 ) complications such as risk of nerve injuries , quadriceps dysfunction , and drainage compared with use of a tourniquet throughout the procedure . Methods Seventy-one patients ( 79 knees ) were r and omized to either use of a tourniquet from the incision through cementation of the implants and deflated for closure ( operative tourniquet group ) or tourniquet use only during cementation ( cementation tourniquet group ) . The initial study population was a minimum of 30 knees in each group as suggested for r and omized studies by American Society for Testing and Material s st and ards ; termination of the study was determined by power analysis performed after 40 knees in each group showed any statistical solution to our questions would require a minimum of 260 more cases . Patients were excluded who were considered in previous r and omized studies as high risk for complications , which might be attributed to the tourniquet . Results There were no differences in terms of surgical time , pain scores , pain medicine requirements , range of motion , hemoglobin change , or total blood loss . One major complication ( compartmental syndrome ) occurred in a patient with tourniquet inflation until closure . No other complications were attributed to the use of a tourniquet . Conclusions With the numbers available , our results suggest that there are no important clinical differences between patients who had a tourniquet inflated throughout the procedure compared with those who had it inflated only during cementation . Tourniquet inflation for cementation only provides the benefit of bloodless bone for fixation and may eliminate the risks associated with prolonged tourniquet use . Level of Evidence Level I , therapeutic study . See Guidelines for Authors for a complete description of levels of evidence BACKGROUND Anterior knee pain is still a major problem in total knee arthroplasty ( TKA ) . Although the most widely accepted opinion is that anterior knee pain is often associated with a patellofemoral etiology , there is no clear consensus as to etiology or treatment . Disabling pain receptors by electrocautery could theoretically achieve denervation of the anterior knee region . The present prospect i ve r and omized controlled study aim ed to evaluate results after patellar denervation with electrocautery in TKA at a minimum follow-up of 2 years . HYPOTHESIS Patellar denervation provides some benefit in terms of pain and clinical outcomes after TKA without patellar resurfacing . PATIENTS AND METHODS Clinical and radiological results for 35 patients with single-stage bilateral TKA ( 70 knees ; 26 women , nine men ; mean age , 68 years [ range , 58 to 77 years ] ) were review ed . In addition to removal of all osteophytes , patellar denervation by electrocautery was performed on one patella ; and debridement alone , removing all osteophytes , was performed on the contralateral patella , as a control . KSS score and a visual analog scale ( VAS ) were used to assess pre- and postoperative anterior knee pain . RESULTS Mean follow-up was 36 months ( 24 to 60 months ) . No revisions or re-operations were performed . There were no patellar fractures . On all parameters ( KSS score , range of motion and VAS ) , there was a statistically significant pre- to postoperative difference in favor of the denervation group . DISCUSSION Patellar denervation with electrocautery can reduce anterior knee pain , with satisfactory clinical and radiological outcome , in TKA without patellar resurfacing . LEVEL OF EVIDENCE Level II : low-powered prospect i ve r and omized trial We r and omized 126 consecutive patients undergoing primary total knee arthroplasty into group 1 : patella denervation ( n = 63 ) and group 2 : no patella denervation ( n = 63 ) . Assessment was performed preoperatively and at 3 , 12 and 24 months post-operatively . Average follow-up of patients was 26.5 months for denervation group and 26.3 months for no denervation group ( P = 0.84 ) . Pain scores for anterior knee pain were significantly better in the denervation group at 3 months but not at 12 and 24 months . Patient satisfaction was higher in the denervation group . Flexion range was higher in the denervation group at 3 , 12 and 24 months review ( P < 0.01 ) . There were , however , no statistically significant differences with other vali date d knee scores Background Adequate and intensive rehabilitation is an important requirement for successful total knee arthroplasty . Although research suggests that Continuous Passive Motion ( CPM ) should be implemented in the first rehabilitation phase after surgery , there is substantial debate about the duration of each session and the total period of CPM application . A Cochrane review on this topic concluded that short-term use of CPM leads to greater short-term range of motion . It also suggested , however , that future research should concentrate on the treatment period during which CPM should be administered . Methods In a r and omised controlled trial we investigated the effectiveness of prolonged CPM use in the home situation as an adjunct to st and ardised PT . Efficacy was assessed in terms of faster improvements in range of motion ( RoM ) and functional recovery , measured at the end of the active treatment period , 17 days after surgery . Sixty patients with knee osteoarthritis undergoing TKA and experiencing early postoperative flexion impairment were r and omised over two treatment groups . The experimental group received CPM + PT for 17 consecutive days after surgery , whereas the usual care group received the same treatment during the in-hospital phase ( i.e. about four days ) , followed by PT alone ( usual care ) in the first two weeks after hospital discharge . From 18 days to three months after surgery , both groups received st and ardised PT . The primary focus of rehabilitation was functional recovery ( e.g. ambulation ) and regaining RoM in the knee . Results Prolonged use of CPM slightly improved short-term RoM in patients with limited RoM at the time of discharge after total knee arthroplasty when added to a semi-st and ard PT programme . Assessment at 6 weeks and three months after surgery found no long-term effects of this intervention Neither did we detect functional benefits of the improved RoM at any of the outcome assessment s. Conclusion Although results indicate that prolonged CPM use might have a small short-term effect on RoM , routine use of prolonged CPM in patients with limited RoM at hospital discharge should be reconsidered , since neither long-term effects nor transfer to better functional performance was detected . Trial Registration IS RCT Minimally invasive surgery has recently been introduced in TKA surgery . The purpose of this study was to evaluate the effect of eversion of the patella , on safety and functional result after TKA . In a prospect i ve , r and omised , double blinded trial , 60 patients were divided in two groups : group A underwent TKA through a st and ard medial parapatellar arthrotomy , with patellar eversion . Group B underwent the same exposure , except for the fact that the patella was subluxed laterally . All other treatment protocol s were identical . Outcomes were measured until 1 year postoperatively . Radiographic evaluation included AP , lateral , skyline and full leg st and ing radiographs . VAS , WOMAC score , Knee Society Knee and Function score were performed . Active and passive range of motion ( ROM ) and knee proprioception was measured . All patients underwent isokinetic strength testing . The mean passive ROM changed from 121 ° preoperatively to 121 ° postoperatively in group A , compared to 118 ° –131 ° respectively in group B at 1 year ( P = 0.003 ) . The mean active ROM changed from 112 ° to 115 ° in group A , and from 108 ° to 125 ° in group B ( P = 0.005 ) . All other parameters were not significantly different . Patellar dislocation without eversion for exposing the knee during TKA is a safe procedure and improves ROM at 1 year postoperatively BACKGROUND There is conflicting evidence regarding the merits of patellar resurfacing during total knee arthroplasty , as many of the previous r and omized controlled trials have not been adequately powered . METHODS A pragmatic , multicenter , r and omized controlled trial was initiated in 1999 in the United Kingdom . Within a partial factorial design , 1715 patients were r and omly allocated to receive or not receive patellar resurfacing during total knee arthroplasty . The primary outcome measure was the Oxford Knee Score ; secondary measures included the Short Form-12 , the EuroQoL 5D , cost , cost-effectiveness , and the need for subsequent knee surgery . RESULTS The mean Oxford Knee Score was 35 points at five years postoperatively in both groups . There was no significant difference between the groups with respect to the mean Oxford Knee Score ( difference , 0.59 point ; 95 % confidence interval , -0.58 to 1.76 points ) or any other outcome measure at five years postoperatively . The outcome was not affected by whether the patella was domed or anatomic . There was no significant difference between the two groups with respect to the prevalence of knee-related readmission , of minor or intermediate reoperation , or of subsequent patella-related surgery . The total health care cost for the primary arthroplasty , subsequent monitoring , and any revision surgery did not differ significantly between the two groups . CONCLUSIONS In the largest r and omized controlled trial of patellar resurfacing reported to date , the functional outcome , reoperation rate , and total health care cost five years after primary total knee arthroplasty were not significantly affected by the addition of patellar resurfacing to the surgical procedure Background and purpose Although a tourniquet may reduce bleeding during total knee replacement ( TKA ) , and thereby possibly improve fixation , it might also cause complications . Migration as measured by radiostereometric analysis ( RSA ) can predict future loosening . We investigated whether the use of a tourniquet influences prosthesis fixation measured with RSA . This has not been investigated previously to our knowledge . Methods 50 patients with osteoarthritis of the knee were r and omized to cemented TKA with or without tourniquet . RSA was performed postoperatively and at 6 months , 1 year , and 2 years . Pain during hospital stay was registered with a visual analog scale ( VAS ) and morphine consumption was measured . Overt bleeding and blood transfusions were registered , and total bleeding was estimated by the hemoglobin dilution method . Range of motion was measured up to 2 years . Results RSA maximal total point motion ( MTPM ) differed by 0.01 mm ( 95 % CI –0.13 to 0.15 ) . Patients in the tourniquet group had less overt bleeding ( 317 mL vs Output:

Do patients need continuous passive motion for their post-surgery rehabilitation ? At the same time , it is becoming apparent that a meticulous operative technique , respecting the soft tissue envelope and knowing the principles of alignment and soft tissue balancing , are some of the parameters that might contribute more to achieving the optimal results for the patients

MS214145

***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: CONTEXT Epinephrine is widely used in cardiopulmonary resuscitation for out-of-hospital cardiac arrest ( OHCA ) . However , the effectiveness of epinephrine use before hospital arrival has not been established . OBJECTIVE To evaluate the association between epinephrine use before hospital arrival and short- and long-term mortality in patients with cardiac arrest . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve , nonr and omized , observational propensity analysis of data from 417 188 OHCAs occurring in 2005 - 2008 in Japan in which patients aged 18 years or older had an OHCA before arrival of emergency medical service ( EMS ) personnel , were treated by EMS personnel , and were transported to the hospital . MAIN OUTCOME MEASURES Return of spontaneous circulation before hospital arrival , survival at 1 month after cardiac arrest , survival with good or moderate cerebral performance ( Cerebral Performance Category [ CPC ] 1 or 2 ) , and survival with no , mild , or moderate neurological disability ( Overall Performance Category [ OPC ] 1 or 2 ) . RESULTS Return of spontaneous circulation before hospital arrival was observed in 2786 of 15,030 patients ( 18.5 % ) in the epinephrine group and 23,042 of 402,158 patients ( 5.7 % ) in the no-epinephrine group ( P < .001 ) ; it was observed in 2446 ( 18.3 % ) and 1400 ( 10.5 % ) of 13,401 propensity-matched patients , respectively ( P < .001 ) . In the total sample , the numbers of patients with 1-month survival and survival with CPC 1 or 2 and OPC 1 or 2 , respectively , were 805 ( 5.4 % ) , 205 ( 1.4 % ) , and 211 ( 1.4 % ) with epinephrine and 18,906 ( 4.7 % ) , 8903 ( 2.2 % ) , and 8831 ( 2.2 % ) without epinephrine ( all P < .001 ) . Corresponding numbers in propensity-matched patients were 687 ( 5.1 % ) , 173 ( 1.3 % ) , and 178 ( 1.3 % ) with epinephrine and 944 ( 7.0 % ) , 413 ( 3.1 % ) , and 410 ( 3.1 % ) without epinephrine ( all P < .001 ) . In all patients , a positive association was observed between prehospital epinephrine and return of spontaneous circulation before hospital arrival ( adjusted odds ratio [ OR ] , 2.36 ; 95 % CI , 2.22 - 2.50 ; P < .001 ) . In propensity-matched patients , a positive association was also observed ( adjusted OR , 2.51 ; 95 % CI , 2.24 - 2.80 ; P < .001 ) . In contrast , among all patients , negative associations were observed between prehospital epinephrine and long-term outcome measures ( adjusted ORs : 1-month survival , 0.46 [ 95 % CI , 0.42 - 0.51 ] ; CPC 1 - 2 , 0.31 [ 95 % CI , 0.26 - 0.36 ] ; and OPC 1 - 2 , 0.32 [ 95 % CI , 0.27 - 0.38 ] ; all P < .001 ) . Similar negative associations were observed among propensity-matched patients ( adjusted ORs : 1-month survival , 0.54 [ 95 % CI , 0.43 - 0.68 ] ; CPC 1 - 2 , 0.21 [ 95 % CI , 0.10 - 0.44 ] ; and OPC 1 - 2 , 0.23 [ 95 % CI , 0.11 - 0.45 ] ; all P < .001 ) . CONCLUSION Among patients with OHCA in Japan , use of prehospital epinephrine was significantly associated with increased chance of return of spontaneous circulation before hospital arrival but decreased chance of survival and good functional outcomes 1 month after the event CONTEXT Intravenous access and drug administration are included in advanced cardiac life support ( ACLS ) guidelines despite a lack of evidence for improved outcomes . Epinephrine was an independent predictor of poor outcome in a large epidemiological study , possibly due to toxicity of the drug or cardiopulmonary resuscitation ( CPR ) interruptions secondary to establishing an intravenous line and drug administration . OBJECTIVE To determine whether removing intravenous drug administration from an ACLS protocol would improve survival to hospital discharge after out-of-hospital cardiac arrest . DESIGN , SETTING , AND PATIENTS Prospect i ve , r and omized controlled trial of consecutive adult patients with out-of-hospital nontraumatic cardiac arrest treated within the emergency medical service system in Oslo , Norway , between May 1 , 2003 , and April 28 , 2008 . INTERVENTIONS Advanced cardiac life support with intravenous drug administration or ACLS without access to intravenous drug administration . MAIN OUTCOME MEASURES The primary outcome was survival to hospital discharge . The secondary outcomes were 1-year survival , survival with favorable neurological outcome , hospital admission with return of spontaneous circulation , and quality of CPR ( chest compression rate , pauses , and ventilation rate ) . RESULTS Of 1183 patients for whom resuscitation was attempted , 851 were included ; 418 patients were in the ACLS with intravenous drug administration group and 433 were in the ACLS with no access to intravenous drug administration group . The rate of survival to hospital discharge was 10.5 % for the intravenous drug administration group and 9.2 % for the no intravenous drug administration group ( P = .61 ) , 32 % vs 21 % , respectively , ( P<.001 ) for hospital admission with return of spontaneous circulation , 9.8 % vs 8.1 % ( P = .45 ) for survival with favorable neurological outcome , and 10 % vs 8 % ( P = .53 ) for survival at 1 year . The quality of CPR was comparable and within guideline recommendations for both groups . After adjustment for ventricular fibrillation , response interval , witnessed arrest , or arrest in a public location , there was no significant difference in survival to hospital discharge for the intravenous group vs the no intravenous group ( adjusted odds ratio , 1.15 ; 95 % confidence interval , 0.69 - 1.91 ) . CONCLUSION Compared with patients who received ACLS without intravenous drug administration following out-of-hospital cardiac arrest , patients with intravenous access and drug administration had higher rates of short-term survival with no statistically significant improvement in survival to hospital discharge , quality of CPR , or long-term survival . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00121524 IMPORTANCE Among patients with cardiac arrest , preliminary data have shown improved return of spontaneous circulation and survival to hospital discharge with the vasopressin-steroids-epinephrine ( VSE ) combination . OBJECTIVE To determine whether combined vasopressin-epinephrine during cardiopulmonary resuscitation ( CPR ) and corticosteroid supplementation during and after CPR improve survival to hospital discharge with a Cerebral Performance Category ( CPC ) score of 1 or 2 in vasopressor-requiring , in-hospital cardiac arrest . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled , parallel-group trial performed from September 1 , 2008 , to October 1 , 2010 , in 3 Greek tertiary care centers ( 2400 beds ) with 268 consecutive patients with cardiac arrest requiring epinephrine according to resuscitation guidelines ( from 364 patients assessed for eligibility ) . INTERVENTIONS Patients received either vasopressin ( 20 IU/CPR cycle ) plus epinephrine ( 1 mg/CPR cycle ; cycle duration approximately 3 minutes ) ( VSE group , n = 130 ) or saline placebo plus epinephrine ( 1 mg/CPR cycle ; cycle duration approximately 3 minutes ) ( control group , n = 138 ) for the first 5 CPR cycles after r and omization , followed by additional epinephrine if needed . During the first CPR cycle after r and omization , patients in the VSE group received methylprednisolone ( 40 mg ) and patients in the control group received saline placebo . Shock after resuscitation was treated with stress-dose hydrocortisone ( 300 mg daily for 7 days maximum and gradual taper ) ( VSE group , n = 76 ) or saline placebo ( control group , n = 73 ) . MAIN OUTCOMES AND MEASURES Return of spontaneous circulation ( ROSC ) for 20 minutes or longer and survival to hospital discharge with a CPC score of 1 or 2 . RESULTS Follow-up was completed in all resuscitated patients . Patients in the VSE group vs patients in the control group had higher probability for ROSC of 20 minutes or longer ( 109/130 [ 83.9 % ] vs 91/138 [ 65.9 % ] ; odds ratio [ OR ] , 2.98 ; 95 % CI , 1.39 - 6.40 ; P = .005 ) and survival to hospital discharge with CPC score of 1 or 2 ( 18/130 [ 13.9 % ] vs 7/138 [ 5.1 % ] ; OR , 3.28 ; 95 % CI , 1.17 - 9.20 ; P = .02 ) . Patients in the VSE group with postresuscitation shock vs corresponding patients in the control group had higher probability for survival to hospital discharge with CPC scores of 1 or 2 ( 16/76 [ 21.1 % ] vs 6/73 [ 8.2 % ] ; OR , 3.74 ; 95 % CI , 1.20 - 11.62 ; P = .02 ) , improved hemodynamics and central venous oxygen saturation , and less organ dysfunction . Adverse event rates were similar in the 2 groups . CONCLUSION AND RELEVANCE Among patients with cardiac arrest requiring vasopressors , combined vasopressin-epinephrine and methylprednisolone during CPR and stress-dose hydrocortisone in postresuscitation shock , compared with epinephrine/saline placebo , result ed in improved survival to hospital discharge with favorable neurological status . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00729794 BACKGROUND There is little evidence from clinical trials that the use of adrenaline ( epinephrine ) in treating cardiac arrest improves survival , despite adrenaline being considered st and ard of care for many decades . The aim of our study was to determine the effect of adrenaline on patient survival to hospital discharge in out of hospital cardiac arrest . METHODS We conducted a double blind r and omised placebo-controlled trial of adrenaline in out-of-hospital cardiac arrest . Identical study vials containing either adrenaline 1:1000 or placebo ( sodium chloride 0.9 % ) were prepared . Patients were r and omly allocated to receive 1 ml aliquots of the trial drug according to current advanced life support guidelines . Outcomes assessed included survival to hospital discharge ( primary outcome ) , pre-hospital return of spontaneous circulation ( ROSC ) and neurological outcome ( Cerebral Performance Category Score - CPC ) . RESULTS A total of 4103 cardiac arrests were screened during the study period of which 601 underwent r and omisation . Documentation was available for a total of 534 patients : 262 in the placebo group and 272 in the adrenaline group . Groups were well matched for baseline characteristics including age , gender and receiving byst and er CPR . ROSC occurred in 22 ( 8.4 % ) of patients receiving placebo and 64 ( 23.5 % ) who received adrenaline ( OR=3.4 ; 95 % CI 2.0 - 5.6 ) . Survival to hospital discharge occurred in 5 ( 1.9 % ) and 11 ( 4.0 % ) patients receiving placebo or adrenaline respectively ( OR=2.2 ; 95 % CI 0.7 - 6.3 ) . All but two patients ( both in the adrenaline group ) had a CPC score of 1 - 2 . CONCLUSION Patients receiving adrenaline during cardiac arrest had no statistically significant improvement in the primary outcome of survival to hospital discharge although there was a significantly improved likelihood of achieving ROSC CONTEXT The health and policy implication s of regional variation in incidence and outcome of out-of-hospital cardiac arrest remain to be determined . OBJECTIVE To evaluate whether cardiac arrest incidence and outcome differ across geographic regions . DESIGN , SETTING , AND PATIENTS Prospect i ve observational study ( the Resuscitation Outcomes Consortium ) of all out-of-hospital cardiac arrests in 10 North American sites ( 8 US and 2 Canadian ) from May 1 , 2006 , to April 30 Output:

In conclusion , in this systematic review and meta- analysis involving studies , the use of epinephrine result ed in a significantly higher likelihood of survival to hospital discharge and ROSC than the non-epinephrine administration , but , there was no significant between group difference in the rate of a favorable neurologic outcome

MS214146

***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 Multiorganisational quality improvement ( QI ) collaborative networks are promoted for improving quality within healthcare . Recently , several large-scale QI initiatives have been conducted in the intensive care unit ( ICU ) environment with successful quantitative results . However , the mechanisms through which such networks lead to QI success remain uncertain . We aim to underst and ICU staff perspectives on collaborative QI based on involvement in a multiorganisational improvement network and hypothesise about theoretical constructs that might explain the effect of collaboration in such networks . Methods Qualitative study using a modified grounded theory approach . Key informant interviews were conducted with staff from 12 community hospital ICUs that participated in a cluster r and omized control trial ( RCT ) of a QI intervention using a collaborative approach between 2006 and 2008 . Data analysis followed the st and ard procedure for grounded theory using constant comparative methodology . Results The collaborative network was perceived to promote increased intrateam cooperation over interorganisational cooperation , but friendly competition with other ICUs appeared to be a prominent driver of behaviour change . Bedsides , clinicians reported that belonging to a collaborative network provided recognition for the high- quality patient care that they already provided . However , the existing communication structure was perceived to be ineffective for staff engagement since it was based on a hierarchical approach to knowledge transfer and project awareness . Conclusions QI collaborative networks may promote behaviour change by improving intrateam communication , fostering competition with other institutions , and increasing recognition for providing high- quality care . Other commonly held assumptions about their potential impact , for instance , increasing interorganisational legitimisation , communication and collaboration , may be less important BACKGROUND The adherence to evidence -based treatment guidelines for acute myocardial infa rct ion ( AMI ) is still suboptimal . Therefore , we design ed a study to evaluate the effects of a collaborative quality improvement ( QI ) intervention on the adherence to AMI guidelines . The intervention used a national web-based quality registry to generate local and regular real-time performance feedback . METHODS A 12-month baseline measurement of the adherence rates was retrospectively collected , comprising the period July 1 , 2001 , through June 30 , 2002 . During the intervention period of November 1 , 2002 , through April 30 , 2003 , multidisciplinary teams from 19 nonr and omized intervention hospitals were subjected to a multifaceted QI-oriented intervention . Another 19 hospitals , unaware of their status as controls , were matched to the intervention hospitals . During the postintervention measurement period of May 1 , 2003 , through April 30 , 2004 , a total of 6726 consecutive patients were included at the intervention ( n = 3786 ) and control ( n = 2940 ) hospitals . The outcome measures comprised 5 Swedish national guideline -derived quality indicators , compared between baseline and postintervention levels in the control and QUICC intervention hospitals . RESULTS In the control and QI intervention hospitals , the mean absolute increase of patients receiving angiotensin-converting enzyme inhibitors was 1.4 % vs 12.6 % ( P = .002 ) , lipid-lowering therapy 2.3 % vs 7.2 % ( P = .065 ) , clopidogrel 26.3 % vs 41.2 % ( P = .010 ) , heparin/low-molecular weight heparin 5.3 % vs 16.3 % ( P = .010 ) , and coronary angiography 6.2 % vs 16.8 % ( P = .027 ) , respectively . The number of QI intervention hospitals reaching a treatment level of at least 70 % in 4 or 5 of the 5 indicators was 15 and 5 , respectively . In the control group , no hospital reached 70 % or more in just 4 of the 5 indicators . CONCLUSIONS By combining a systematic and multidisciplinary QI collaborative with a web-based national quality registry with functionality allowing real-time performance feedback , major improvements in the adherence to national AMI guidelines can be achieved Background Quality improvement collaboratives ( QIC ) have proliferated internationally , but there is little empirical evidence for their effectiveness . Method We search ed Medline , Embase , CINAHL , PsycINFO and the Cochrane Library data bases from January 1995 to December 2014 . Studies were included if they met the criteria for a QIC intervention and the Cochrane Effective Practice and Organisation of Care ( EPOC ) minimum study design characteristics for inclusion in a review . We assessed study bias using the EPOC checklist and the quality of the reported intervention using a subset of SQUIRE 1.0 st and ards . Results Of the 220 studies meeting QIC criteria , 64 met EPOC study design st and ards for inclusion . There were 10 cluster r and omised controlled trials , 24 controlled before-after studies and 30 interrupted time series studies . QICs encompassed a broad range of clinical setting s , topics and population s ranging from neonates to the elderly . Few reports fully described QIC implementation and methods , intensity of activities , degree of site engagement and important context ual factors . By care setting , an improvement was reported for one or more of the study ’s primary effect measures in 83 % of the studies ( 32/39 ( 82 % ) hospital based , 17/20 ( 85 % ) ambulatory care , 3/4 nursing home and a sole ambulance QIC ) . Eight studies described persistence of the intervention effect 6 months to 2 years after the end of the collaborative . Collaboratives reporting success generally addressed relatively straightforward aspects of care , had a strong evidence base and noted a clear evidence - practice gap in an accepted clinical pathway or guideline . Conclusions QICs have been adopted widely as an approach to shared learning and improvement in healthcare . Overall , the QICs included in this review reported significant improvements in targeted clinical processes and patient outcomes . These reports are encouraging , but most be interpreted cautiously since fewer than a third met established quality and reporting criteria , and publication bias is likely Background : Continuous Quality Improvement ( CQI ) is a process where health teams systematic ally collect and regularly reflect on local data to inform decisions and modify local practice s and so improve delivery of services . We implemented a cluster r and omized trial to examine the effects of CQI interventions on Prevention of Mother-to-Child Transmission ( PMTCT ) services . Here , we report our experiences and challenges establishing CQI in 2 high HIV prevalence states in northern Nigeria . Methods : Facility-based teams were trained to implement CQI activities , including structured assessment s , developing change packages , and participation in periodic collaborative learning sessions . Locally evolved solutions ( change ideas ) were tested and measured using process data and intermediate process indicators were agreed including overall time spent accessing services , client satisfaction , and quality of data . Results : Health workers actively participated in clinic activities and in the collaborative learning sessions . During the study , the mean difference in time spent accessing services during clinic visits increased by 40 minutes ( SD = 93.4 ) in the control arm and decreased by 44 minutes ( SD = 73.7 ) in the intervention arm . No significant difference was recorded in the mean client satisfaction assessment score by study arm . The quality of data was assessed using a st and ardized tool scored out of 100 ; compared with baseline data , quality at the end of study had improved at intervention sites by 6 points ( 95 % CI : 2.0 to 10.1 ) . Conclusions : Health workers were receptive to CQI process . A compendium of “ change ideas ” compiled into a single change package can be used to improve health care delivery Background Maternal , perinatal and neonatal mortality remains high in low-income countries . We evaluated community and facility-based interventions to reduce deaths in three districts of Malawi . Methods We evaluated a rural participatory women ’s group community intervention ( CI ) and a quality improvement intervention at health centres ( FI ) via a two-by-two factorial cluster r and omized controlled trial . Consenting pregnant women were followed-up to 2 months after birth using key informants . Primary outcomes were maternal , perinatal and neonatal mortality . Clusters were health centre catchment areas assigned using stratified computer-generated r and omization . Following exclusions , including non-birthing facilities , 61 clusters were analysed : control ( 17 clusters , 4912 births ) , FI ( 15 , 5335 ) , CI ( 15 , 5080 ) and FI + CI ( 14 , 5249 ) . This trial was registered as International St and ard R and omised Controlled Trial [ IS RCT N18073903 ] . Outcomes for 14 576 and 20 576 births were recorded during baseline ( June 2007–September 2008 ) and intervention ( October 2008–December 2010 ) periods . Results For control , FI , CI and FI + CI clusters neonatal mortality rates were 34.0 , 28.3 , 29.9 and 27.0 neonatal deaths per 1000 live births and perinatal mortality rates were 56.2 , 55.1 , 48.0 and 48.4 per 1000 births , during the intervention period . Adjusting for clustering and stratification , the neonatal mortality rate was 22 % lower in FI + CI than control clusters ( OR = 0.78 , 95 % CI 0.60–1.01 ) , and the perinatal mortality rate was 16 % lower in CI clusters ( OR = 0.84 , 95 % CI 0.72–0.97 ) . We did not observe any intervention effects on maternal mortality . Conclusions Despite implementation problems , a combined community and facility approach using participatory women ’s groups and quality improvement at health centres reduced newborn mortality in rural Malawi Background The Medical Research Councils ’ framework for complex interventions has been criticized for not including theory-driven approaches to evaluation . Although the framework does include broad guidance on the use of theory , it contains little practical guidance for implementers and there have been calls to develop a more comprehensive approach . A prospect i ve , theory-driven process of intervention design and evaluation is required to develop complex healthcare interventions which are more likely to be effective , sustainable and scalable . Methods We propose a theory-driven approach to the design and evaluation of complex interventions by adapting and integrating a programmatic design and evaluation tool , Theory of Change ( ToC ) , into the MRC framework for complex interventions . We provide a guide to what ToC is , how to construct one , and how to integrate its use into research projects seeking to design , implement and evaluate complex interventions using the MRC framework . We test this approach by using ToC within two r and omized controlled trials and one non-r and omized evaluation of complex interventions . Results Our application of ToC in three research projects has shown that ToC can strengthen key stages of the MRC framework . It can aid the development of interventions by providing a framework for enhanced stakeholder engagement and by explicitly design ing an intervention that is embedded in the local context . For the feasibility and piloting stage , ToC enables the systematic identification of knowledge gaps to generate research questions that strengthen intervention design . ToC may improve the evaluation of interventions by providing a comprehensive set of indicators to evaluate all stages of the causal pathway through which an intervention achieves impact , combining evaluations of intervention effectiveness with detailed process evaluations into one theoretical framework . Conclusions Incorporating a ToC approach into the MRC framework holds promise for improving the design and evaluation of complex interventions , thereby increasing the likelihood that the intervention will be ultimately effective , sustainable and scalable . We urge research ers developing and evaluating complex interventions to consider using this approach , to evaluate its usefulness and to build an evidence base to further refine the methodology .Trial registration Clinical trials.gov : Deficiencies in the quality and safety of health care remain a significant concern in the United States and abroad as evidence documenting gaps between actual and recommended clinical practice s continues to accumulate ( 1 , 2 ) . The significance of the well-recognized health care quality chasm has been acknowledged by a broad array of stakeholders , who have responded with efforts to identify , underst and , and correct specific shortcomings in health care delivery . The quality improvement collaborative ( QIC ) examined by L and on and colleagues in this issue ( 3 ) is arguably the health care delivery industry 's most important response to quality and safety gaps ; it represents substantial investments of time , effort , and funding . Largely developed and popularized by the Boston-based Institute for Healthcare Improvement ( IHI ) and best exemplified by IHI 's Breakthrough Series collaborative program , the QIC method has been adopted on a large scale by the U.S. Health Re sources and Services Administration ( HRSA ) ( 4 ) and the United Kingdom 's National Health Service ( NHS ) ( 5 ) . The Veterans Health Administration ( 6 ) and numerous smaller health care systems and individual hospitals and clinics worldwide have adopted the method on a smaller scale ( 7 ) . The QIC method brings together a group of participating ( collaborating ) health care delivery organizations ( typically between 20 and 40 ) and guides them in study ing a specific health care quality problem , design ing and implementing specific solutions , evaluating and refining these solutions , and disseminating findings to other organizations . Each participating organization is represented by a 3- or 4-person team ; all teams meet together with a small faculty of experts in a series of 2 or 3 multiday collaborative learning session meetings , which take place over several months . During the meetings , the team members learn improvement techniques , exchange insights and advice , and generate enthusiasm and a shared sense of commitment to achieving common improvement goals and outcomes . Teams return to their organizations between learning sessions to apply their new knowledge and ideas in a Pl anD o Study Act framework ( 8) . They conduct repeated cycles of quality problem diagnosis , development and implementation of small-scale improvement efforts , assessment of effects , and refinement and expansion of effective actions until desired outcomes are achieved . The QIC method is described in detail elsewhere ( 7 Output:

Adequacy and appropriateness of external support , functionality of quality improvement teams , leadership characteristics and alignment with national systems and priorities may influence outcomes of quality improvement collaboratives , but the strength and quality of the evidence is weak . Participation in quality improvement collaborative activities may improve health professionals ’ knowledge , problem-solving skills and attitude ; teamwork ; shared leadership and habits for improvement . Interaction across quality improvement teams may generate normative pressure and opportunities for capacity building and peer recognition .

MS214147

***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: CONTEXT Abacavir , a nucleoside analogue , has demonstrated suppression of human immunodeficiency virus ( HIV ) replication alone and in combination therapy . However , the role of abacavir in a triple nucleoside combination regimen has not been evaluated against a st and ard protease inhibitor-containing regimen for initial antiretroviral treatment . OBJECTIVE To evaluate antiretroviral equivalence and safety of an abacavir-lamivudine-zidovudine regimen compared with an indinavir-lamivudine-zidovudine regimen . DESIGN AND SETTING A multicenter , phase 3 , r and omized , double-blind trial with an enrollment period from August 1997 to June 1998 , with follow-up through 48 weeks at 73 clinical research units in the United States , Canada , Australia , and Europe . PATIENTS Five hundred sixty-two antiretroviral-naive , HIV-infected adults with a plasma HIV RNA level of at least 10 000 copies/mL and a CD4 cell count of at least 100 x 10(6)/L. INTERVENTIONS Patients were stratified by baseline HIV RNA level and r and omly assigned to receive a combination tablet containing 150 mg of lamivudine and 300 mg of zidovudine twice daily plus either 300 mg of abacavir twice daily and indinavir placebo or 800 mg of indinavir every 8 hours daily plus abacavir placebo . After 16 weeks , patients with confirmed HIV RNA levels greater than 400 copies/mL were eligible to continue receiving r and omized treatment or receive open-label therapy . MAIN OUTCOME MEASURE Virologic suppression , defined as HIV RNA concentration of 400 copies/mL or less at week 48 . RESULTS The proportion of patients who met the end point of having an HIV RNA level of 400 copies/mL or less at week 48 was equivalent in the abacavir group ( 51 % [ 133/262 ] ) and in the indinavir group ( 51 % [ 136/265 ] ) with a treatment difference of -0.6 % ( 95 % confidence interval [ CI ] , -9 % to 8 % ) . In patients with baseline HIV RNA levels greater than 100 000 copies/mL , the proportion of patients achieving less than 50 copies/mL was greater in the indinavir group than in the abacavir group with 45 % ( 45/100 ) vs 31 % ( 30/96 ) and a treatment diference of -14 % ( 95 % CI , -27 % to 0 % ) . The 2 treatments were comparable with respect to their effects on CD4 cell count . There was no difference between groups in the frequency of treatment-limiting adverse events or laboratory abnormalities . One death in the abacavir group was attributed to hypersensitivity reaction , which occurred following rechallenge with abacavir , approximately 3 weeks after initiating study treatment . CONCLUSIONS In this study of antiretroviral-naive HIV-infected adults , the triple nucleoside regimen of abacavir-lamivudine-zidovudine was equivalent to the regimen of indinavir-lamivudine-zidovudine in achieving a plasma HIV RNA level of less than 400 copies/mL at 48 weeks Patients with sustained virological suppression on protease inhibitor (PI)-based therapy were r and omly assigned to switch the PI to nevirapine ( n = 155 ) , efavirenz ( n = 156 ) , or abacavir ( n = 149 ) and were followed for at least 3 years regardless of the discontinuation of assigned therapy . There was a higher probability of maintaining virological suppression after 3 years of follow-up with nevirapine or efavirenz than with abacavir . In contrast , abacavir showed a lower incidence of adverse effects leading to drug discontinuation BACKGROUND Evidence from r and omized controlled trials supports the use of triple therapy . Research is required on the effectiveness of quadruple therapy in comparison to this and the relative effectiveness of specific highly active antiretroviral therapy ( HAART ) combinations . METHODS Antiretroviral-naive individuals ( n = 53 ) with an HIV-1 viral load > 100 000 copies/mL were r and omized to receive three-drug HAART with zidovudine/lamivudine ( Combivir ) and efavirenz or quadruple therapy with zidovudine/lamivudine/abacavir ( Trizivir ) and efavirenz ( quad regimen ) . Patients continued on HAART for 48 weeks with regular clinical and immunological assessment . St and ard and ultrasensitive ( < 5 copies/mL ) viral load testing was carried out . RESULTS A DAVG ( difference in averages ) analysis of the fall in viral load and increase in CD4 count showed no significant differences between regimens . Triple therapy result ed in a -4.17 log change ( 95 % CI , -4.48 to -3.85 ) and quadruple therapy in a -4.36 log change ( 95 % CI , -4.68 to -4.03 ) in viral load . For CD4 counts , the triple therapy arm increased by 164 cells/mm(3 ) ( 95 % CI 112 - 217 ) and the quadruple arm by 185 ( 95 % CI , 133 - 237 ) . In an intent-to-treat analysis , 77 % of patients in the triple therapy group reached an undetectable viral load ( < 50 copies/mL ) compared with 84.2 % of the quadruple therapy group . For ultrasensitive viral load testing , 23 % and 18 % of each group , respectively , reached undetectable viral loads . The hazard ratio for attaining a viral load of < 5 copies/mL was 0.59 ( 95 % CI , 0.26 - 1.33 ) for quadruple versus triple therapy . Three individuals in the triple therapy arm and nine in the quadruple therapy arm discontinued treatment . CONCLUSIONS No differences in any analyses were observed between a st and ard of care regimen ( zidovudine/lamivudine and efavirenz ) and the quad regimen ( zidovudine/lamivudine/abacavir and efavirenz ) BACKGROUND The use of fixed-dose combination nucleoside reverse-transcriptase inhibitors ( NRTIs ) with a nonnucleoside reverse-transcriptase inhibitor or a ritonavir-boosted protease inhibitor is recommended as initial therapy in patients with human immunodeficiency virus type 1 ( HIV-1 ) infection , but which NRTI combination has greater efficacy and safety is not known . METHODS In a r and omized , blinded equivalence study involving 1858 eligible patients , we compared four once-daily antiretroviral regimens as initial therapy for HIV-1 infection : abacavir-lamivudine or tenofovir disoproxil fumarate (DF)-emtricitabine plus efavirenz or ritonavir-boosted atazanavir . The primary efficacy end point was the time from r and omization to virologic failure ( defined as a confirmed HIV-1 RNA level > or = 1000 copies per milliliter at or after 16 weeks and before 24 weeks , or > or = 200 copies per milliliter at or after 24 weeks ) . RESULTS A scheduled interim review by an independent data and safety monitoring board showed significant differences in virologic efficacy , according to the NRTI combination , among patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more . At a median follow-up of 60 weeks , among the 797 patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more , the time to virologic failure was significantly shorter in the abacavir-lamivudine group than in the tenofovir DF-emtricitabine group ( hazard ratio , 2.33 ; 95 % confidence interval , 1.46 to 3.72 ; P<0.001 ) , with 57 virologic failures ( 14 % ) in the abacavir-lamivudine group versus 26 ( 7 % ) in the tenofovir DF-emtricitabine group . The time to the first adverse event was also shorter in the abacavir-lamivudine group ( P<0.001 ) . There was no significant difference between the study groups in the change from the baseline CD4 cell count at week 48 . CONCLUSIONS In patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more , the times to virologic failure and the first adverse event were both significantly shorter in patients r and omly assigned to abacavir-lamivudine than in those assigned to tenofovir DF-emtricitabine . ( Clinical Trials.gov number , NCT00118898 . OBJECTIVE To compare the efficacy and safety of fixed-dose abacavir/lamivudine ( ABC/3TC ) and tenofovir/emtricitabine ( TDF/FTC ) with ritonavir-boosted atazanavir ( ATV/r ) in treatment-naïve Japanese patients with HIV-1 infection . METHODS A 96-week multicenter , r and omized , open-label , parallel group pilot study was conducted . The endpoints were times to virologic failure , safety event and regimen modification . RESULTS 109 patients were enrolled and r and omly allocated ( 54 patients received ABC/3TC and 55 patients received TDF/FTC ) . All r and omized subjects were analyzed . The time to virologic failure was not significantly different between the two arms by 96 weeks ( HR , 2.09 ; 95 % CI , 0.72 - 6.13 ; p=0.178 ) . Both regimens showed favorable viral efficacy , as in the intention-to-treat population , 72.2 % ( ABC/3TC ) and 78.2 % ( TDF/FTC ) of the patients had an HIV-1 viral load < 50 copies/mL at 96 weeks . The time to the first grade 3 or 4 adverse event and the time to the first regimen modification were not significantly different between the two arms ( adverse event : HR 0.66 ; 95 % CI , 0.25 - 1.75 , p=0.407 ) ( regimen modification : HR 1.03 ; 95 % CI , 0.33 - 3.19 , p=0.964 ) . Both regimens were also well-tolerated , as only 11.1 % ( ABC/3TC ) and 10.9 % ( TDF/FTC ) of the patients discontinued the allocated regimen by 96 weeks . Clinical ly suspected abacavir-associated hypersensitivity reactions occurred in only one ( 1.9 % ) patient in the ABC/3TC arm . CONCLUSION Although insufficiently powered to show non-inferiority of viral efficacy of ABC/3TC relative to TDF/FTC , this pilot trial suggested that ABC/3TC with ATV/r is a safe and efficacious initial regimen for HLA-B*5701-negative patients , such as the Japanese population Background : Long-term antiretroviral therapy , while dramatically reducing HIV-related morbidity and mortality , is associated with metabolic and morphological changes . Peripheral fat loss , lipoatrophy , appears most associated with prolonged therapy with thymidine nucleoside analogues . Methods : A r and omized , open-label , comparative study of switching from a thymidine nucleoside analogue to either tenofovir disoproxil fumarate ( DF ) or abacavir in 105 individuals on successful antiretroviral therapy with clinical ly evident moderate to severe lipoatrophy . Results : Individuals were r and omized to tenofovir DF ( 52 ) or abacavir ( 53 ) . The switch was well tolerated and the majority of patients completed 48 weeks of study . One individual in the tenofovir DF group and three in the abacavir group discontinued due to drug-related adverse events . Both groups similarly maintained virological control . Limb fat mass increased similarly in both groups : mean increases by week 48 of 329 and 483 g in tenofovir DF and abacavir groups , respectively [ mean 95 % confidence interval for difference , −154.3 ( range −492.8 to 184.3 ) ] . This change from baseline was statistically significant in both groups ( tenofovir DF , P = 0.01 ; abacavir , P = 0.0001 ) . Mean total cholesterol , low density lipoprotein cholesterol and triglycerides improved modestly with switching to tenofovir DF but were unchanged with abacavir . The changes in these parameters were significantly greater in the tenofovir DF arm relative to abacavir . Conclusions : Switching from a thymidine nucleoside analogue to either tenofovir DF or abacavir leads to significant improvement in limb fat mass over 48 weeks . Tenofovir DF may have modest advantages over abacavir for changes in lipids . Peripher Output:

Our cumulative , cross-sectional data suggest a similar virological efficacy of abacavir/lamivudine and tenofovir/emtricitabine regardless of the baseline VL

MS214148

***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 Twenty subjects were treated with either polidocanol ( POL ) or sodium tetradecyl sulfate ( STS ) to compare the efficacy and adverse sequelae of each agent . Objective To determine the safety and efficacy of two widely used sclerosing agents . Methods After the exclusion of saphenofemoral junction incompetency , each subject 's leg veins were categorized by size ( < 1 , 1–3 , and 3–6 mm in diameter ) . Each leg was then r and omized to be treated with 0.5 % , 1 % , or 1 % foam of POL or 0.25 % , 0.5 % , or 0.5 % foam of STS according to vein size . An independent panel of four physicians , blinded to treatment , performed r and omized photographic evaluations obtained pretreatment and 12 weeks post-treatment . Subject satisfaction index and overall clinical improvement assessment were also obtained . Results An average 83 % improvement was noted for all vein sizes in all subjects with both POL and STS after a single treatment . Subjects were satisfied with treatment , regardless of the sclerosing agent used or the vein size treated . There was no statistically significant difference in adverse effects between each group . Conclusion Both POL and STS are safe and effective sclerosing agents in the treatment of varicose and telangiectatic leg veins . Both are very tolerable and demonstrate similar post-treatment sequelae OBJECTIVE The aim of this r and omized study was to compare a new method of endovenous saphenous vein obliteration ( Closure System , VNUS Medical Technologies , Inc , Sunnyvale , Calif ) with the conventional stripping operation in terms of short-term recovery and costs . METHODS Twenty-eight selected patients for operative treatment of primary greater saphenous vein tributary varicose veins were r and omly assigned to endovenous obliteration ( n = 15 ) or stripping operation ( n = 13 ) . Postoperative pain was daily assessed during the 1st week and on the 14th postoperative day . The length of sick leave was determined . The R AND -36 health survey was used to assess the patient health-related quality of life . The patient conditions were controlled 7 to 8 weeks after surgery , and patients underwent examination with duplex ultrasonography . The comparison of costs included both direct medical costs and costs result ing from lost of productivity of the patients . Costs that were similar in the study groups were not considered in the analysis . RESULTS All operations were successful , and the complication rates were similar in the two groups . Postoperative average pain was significantly less severe in the endovenous obliteration group as compared with the stripping group ( at rest : 0.7 , st and ard deviation [ SD ] 0.5 , versus 1.7 , SD 1.3 , P = .017 ; on st and ing : 1.3 , SD 0.7 , versus 2.6 , SD 1.9 , P = .026 ; on walking : 1.8 , SD 0.8 , versus 3.0 , SD 1.8 , P = .036 ; with t test ) . The sick leaves were significantly shorter in the endovenous obliteration group ( 6.5 days , SD 3.3 days , versus 15.6 days , SD 6.0 days ; 95 % CI , 5.4 to 12.9 ; P < .001 , with t test ) . Physical function was also restored faster in the endovenous obliteration group . The estimated annual investment costs of the closure operation were US $ 3360 . The other direct medical costs of the Closure operation were about $ 850 , and those of the conventional treatment were $ 360 . With inclusion of the value of the lost working days , the Closure treatment was cost-saving for society , and when 40 % of the patients are retired ( or 60 % of the productivity loss was included ) , the Closure procedure became cost-saving at a level of 43 operations per year . CONCLUSION Endovenous obliteration may offer advantages over the conventional stripping operation in terms of reduced postoperative pain , shorter sick leaves , and faster return to normal activities , and it appears to be cost-saving for society , especially among employed patients . Because the procedure is also associated with shorter convalescence , this new method may potentially replace conventional varicose vein surgery STUDY OBJECTIVE : To determine the prevalence of varicose veins and chronic venous insufficiency ( CVI ) in the general population . DESIGN : Cross sectional survey . SETTING : City of Edinburgh . PARTICIPANTS : Men and women aged 18 - 64 years selected r and omly from age-sex registers of 12 general practice s. MAIN RESULTS : In 1566 subjects examined , the age adjusted prevalence of trunk varices was 40 % in men and 32 % in women ( p < or = 0.01 ) . This sex difference was mostly a result of higher prevalence of mild trunk varices in men . More than 80 % of all subjects had mild hyphenweb and reticular varices . The age adjusted prevalence of CVI was 9 % in men and 7 % in women ( p < or = 0.05 ) . The prevalence of all categories of varices and of CVI increased with age ( p < or = 0.001 ) . No relation was found with social class . CONCLUSIONS : Approximately one third of men and women aged 18 - 64 years had trunk varices . In contrast with the findings in most previous studies , mainly conducted in the 1960s and 1970s , chronic venous insufficiency and mild varicose veins were more common in men than women . No evidence of bias in the study was found to account for this sex difference . Changes in lifestyle or other factors might be contributing to an alteration in the epidemiology of venous disease BACKGROUND Endovascular radiofrequency obliteration has been used as an alternative to conventional vein-stripping surgery for elimination of saphenous vein insufficiency . A clinical registry was established in 1998 , and its mid-term results have been reported previously . This study is to demonstrate the long-term treatment outcomes and to determine the risk factors that affect treatment efficacy . METHODS Data were collected in an ongoing multicenter , prospect i ve registry . Patients were treated before October 2004 . Clinical and duplex ultrasound follow-up was performed 1 week , 6 months , 1 year , and yearly thereafter to 5 years . Treatment efficacy and clinical improvement after the procedure were analyzed . Three types of anatomical failure were identified . Logistic regression analysis was performed to determine the existence of any significant risk factors associated with anatomical failure . Risk factors considered were age , gender , body mass index , vein diameter , and pullback speed . The impact of anatomical failure on clinical symptoms and varicose vein recurrence was also analyzed . RESULTS There were 1,006 patients ( 1,222 limbs ) treated , their mean age was 47.4 + /- 12.1 years , and 78.1 % were female . Veins treated included 89.1 % great saphenous vein above-knee segments , 1.2 % great saphenous vein below-knee segments , 4.1 % great saphenous vein groin-to-ankle , 4.3 % small saphenous veins , and 1.3 % accessory saphenous veins . Mean vein diameter was 7.5 mm , with a maximum of 24 mm . Vein occlusion rates were 87.1 % , 88.2 % , 83.5 % , 84.9 % , and 87.2 % , and reflux-free rates were 88.2 % , 88.2 % , 88.0 % , 86.6 % , and 83.8 % at each annual follow-up . Clinical symptom improvement was seen in 70 % to 80 % of limbs with anatomical failures and in 85 % to 94 % of limbs with anatomical success from 6 months to 5 years after the radiofrequency obliteration . Logistic regression analysis showed that catheter pullback speed ( P < .0001 ) and body mass index ( P < .0333 ) were risk factors for anatomical failure . Limbs that had type II and type III anatomical failures were found to be more prone to varicose vein recurrence . CONCLUSIONS Endovascular radiofrequency obliteration of saphenous vein reflux exhibits enduring efficacy . Adequate pullback speed during the procedure should be emphasized to ensure the proper thermal dose delivery . A whole treatment strategy to address hemodynamically significant tributaries and perforators can further improve treatment outcomes . Body mass index is a risk factor for anatomical failure , indicating the impact of hemodynamic factors on disease progression and recurrence AIM The innovations for disease management need to be thoroughly evaluated so that their benefits and potential downsides can be compared with the already existing approaches . Endovascular laser ( EVL ) treatment for varicose veins offers today several advantages over surgical st and ard stripping . The Italian Endovenous-laser Working Group ( IEWG ) is a homogeneous group of surgeons and phlebologists who have been using EVL since 1999 and has undertaken to examine EVL in a multicenter study starting from a well defined rationale , with the benefit of a single protocol to use . METHODS In a cooperative , multicenter , clinical study , 1076 limbs in 1050 patients , mean age of 54.5 years , 241 males and 809 females affected by chronic venous insufficiency ( CVI ) were considered eligible for surgery and stratified by CEAP classification in a four-year period ( January 1999 December 2003 ) . Inclusion criteria were insufficiency of the great and /or small saphenous vein at various levels , beyond those accessory saphenous trunks with incompetence in the saphenofemoral junction . In all cases truncular reflux apparead up on duplex scan examination , with or without associated varicosities . All the patients underwent a surgery on the basis of the clinical assessment . All the centres involved performed treatment in conformity with the Food and Drug Administration ( FDA ) vali date d procedure , using an endo-laser venous system kit with a 810 - 980 nm diode . Duplex scan was performed in all patients after 36 months with very few lost to follow-up cases . RESULTS In the immediate postoperative period the results have been impressive , with a very effective closure of incompetent great saphenous vein and the other treated varicose veins ( the early occlusion rate has been 99 % ) . Major complications have not been detected : in particular , no deep venous thrombosis ( DVT ) evaluated duplex ultrasound . The patients ' acceptability and satisfaction regarding the procedure , have been measured by means of a question naire on the quality of life , and the result was 96.7 % . After 36 months , the total occusion rate of saphenous trunks has been 97 % . CONCLUSIONS The first important Italian experience with EVL based on preoperative , perioperative and postoperative duplex control and which is also based on the patients ' satisfaction at mid/long-term has indicated some advantages over the st and ard treatment with the stripping method . In terms of reduced postoperative pain , shorter sick leave , a faster resumption of the normal activities , and , in particular , the total absence of DVT , we can conclude that EVL is a good solution for all patients with anatomic and hemodinamic patterns for saphenous vein surgery The study was planned to evaluate efficacy and costs of endovascular sclerotherapy ( ES ) in comparison with surgery and surgery associated with sclerotherapy in a prospect i ve ( 10-year follow-up ) , good- clinical - practice study . Patients with varicose veins and pure , superficial venous incompetence were included . Of the patients r and omized into the three groups 39 ( group A ) were treated with ES , 40 ( B ) with surgery + sclerotherapy , and 42 with surgery only ( C ) . Surgery consisted of ligation of the SFJ ( saphenofemoral junction ) and of incompetent veins detected with color duplex . Of the preselected 150 patients , 121 subjects entered the study ; 96 completed the 10-year follow-up ( mean age 52.6 ±6 years ; 51 men , 45 women ) . Dropouts were due to nonmedical problems . At 10 years no incompetence was observed in subjects treated with SPJ ligation ( B and C ) . In the ES group 18.8 % of the SFJs were patent and incompetent and in 43.8 % of limbs the distal ( below-knee ) venous system was still incompetent [ 16.1 % in the surgery + scle rotherapy group ( p < 0.05 ) and 36 % in the group treated with surgery only ( p < 0.05 vs B and 0.05 vs A ) ] . Color duplex of the long saphenous vein indicated atrophy or obstruc tion of a segment ( average 6.7 cm ) after SFJ ligation ( 4.2 cm after ES ) . The cost of ES was 68 % of surgery while the cost of surgery and sclerotherapy was 122 % of surgery only . Endovascular sclerotherapy is an effective , cheaper treatment option , but surgery after 10 years is superior OBJECTIVE The purpose of this study was to investigate the possible long-term clinical advantages of stripping the long saphenous vein during routine primary varicose vein surgery . METHODS The study was design ed as a 5-year , clinical and duplex scan follow-up examination of a group of patients who were r and omized to stripping of the long saphenous vein during varicose vein surgery versus saphenofemoral ligation alone . The study was conducted in the vascular unit of a Output:

In the absence of large , comparative r and omized clinical trials , the minimally invasive techniques appear to be at least as effective as surgery in the treatment of lower extremity varicose veins

MS214149

***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 Long-term maintenance of weight loss remains a therapeutic challenge in obesity treatment . OBJECTIVE This multicenter , double-blind , placebo-controlled study was design ed to test the hypothesis that orlistat , a gastrointestinal lipase inhibitor , is significantly more effective than a placebo in preventing weight regain . DESIGN Obese subjects who lost > or = 8 % of their initial body weight during a 6-mo lead-in of a prescribed hypoenergetic diet ( 4180-kJ/d deficit ) with no adjunctive pharmacotherapy were r and omly assigned to receive placebo , 30 mg orlistat , 60 mg orlistat , or 120 mg orlistat 3 times daily for 1 y in combination with a maintenance diet to help prevent weight regain . Of 1313 recruited subjects [ body mass index ( in kg/m2 ) : 28 - 43 ] , 729 subjects lost > or = 8 % of their initial body weight during the 6-mo weight-loss lead-in period and were enrolled in the double-blind phase . RESULTS After 1 y , subjects treated with 120 mg orlistat 3 times daily regained less weight than did placebo-treated subjects ( 32.8 + /- 4.5 % compared with 58.7 + /- 5.8 % regain of lost weight ; P < 0.001 ) . Moreover , more subjects in the 120-mg orlistat group than in the placebo group regained < or = 25 % of lost weight ( 47.5 % of subjects compared with 29.9 % ) . In addition , orlistat treatment ( 120 mg 3 times daily ) was associated with significantly greater reductions in total and LDL-cholesterol concentrations than was placebo ( P < 0.001 ) . CONCLUSION The use of orlistat during periods of attempted weight maintenance minimizes weight readjustment and facilitates long-term improvement in obesity-related disease risk factors OBJECTIVE To evaluate the long-term efficacy and tolerability within primary care setting s of orlistat , a gastrointestinal lipase inhibitor , for the treatment of obesity . DESIGN R and omized , double-blind , placebo-controlled , multicenter study . PARTICIPANTS A group of 796 obese patients ( body mass index , 30 - 44 kg/m2 ) , treated with placebo 3 times a day ( TID ) , 60 mg of orlistat TID , or 120 mg of orlistat TID , in conjunction with a reduced-energy diet for the first year and a weight-maintenance diet during the second year . SETTING Seventeen primary care centers in the United States . MAIN OUTCOME MEASURES Changes in body weight and obesity-related disease risk factors . RESULTS Patients treated with orlistat lost significantly more weight ( 7.08 + /- 0.54 and 7.94 + /- 0.57 kg for the 60-mg and 120-mg orlistat groups , respectively ) than those treated with placebo ( 4.14 + /- 0.56 kg ) in year 1 ( P<.001 ) and sustained more of this weight loss during year 2 ( P<.001 ) . More patients treated with orlistat lost 5 % or more of their initial weight in year 1 ( 48.8 % and 50.5 % of patients in the 60-mg and 120-mg groups , respectively ) compared with placebo ( 30.7 % ; P<.001 ) , and approximately 34 % of patients in the orlistat groups sustained weight loss of 5 % or greater over 2 years compared with 24 % in the placebo group ( P<.001 ) . Orlistat produced greater improvements than placebo in serum lipid levels and blood pressure and was well tolerated , although treatment result ed in a higher incidence of gastrointestinal events . CONCLUSIONS This long-term study indicates that orlistat is an effective adjunct to dietary intervention in the treatment of obesity in primary care setting Reporting harms may cause more trouble and discredit than the fame and glory associated with successful reporting of benefits ( 1 ) . The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement , a checklist ( Table 1 ) flow diagram first published in 1996 and revised 5 years later ( 2 , 3 ) , is an effort to st and ardize , and thereby improve , published reports of r and omized , controlled trials ( RCTs ) . One of the additions to the 2001 revision was an item about reporting adverse events . This single item did not do full justice to the importance of harms-related issues . The CONSORT Group met in September 2001 to discuss how to correct this deficiency . We aim ed to provide evidence -based guidance on the reporting of harms in RCTs . First , we search ed MEDLINE , EMBASE , Web of Science , and the Cochrane Library using a wide array of terms related to harms and identified pertinent evidence . We also communicated with experts and review ed bibliographies of identified articles to find additional studies . At a meeting in Montebello , Quebec , Canada , in May 2003 , CONSORT Group members , including several journal editors and additional experts in related fields , held a structured discussion of recommendations about reporting of harms-related issues in RCTs . The discussion s led to a written document that we circulated among the team members for comment . The present manuscript describes our recommendations on the appropriate reporting of harms in RCTs . Table 1 . Original CONSORT Checklist The terminology of harms-related issues in RCTs is confusing and often misleading or misused ( see Glossary ) ( 4 , 5 ) . Safety is a reassuring term that may obscure the real and potentially major harms that drugs and other interventions may cause . We encourage authors to use the term harms instead of safety . In addition to misused terminology , reporting of harms in RCTs has received less attention than reporting of efficacy and effectiveness and is often inadequate ( 6 - 14 ) . In short , both scientific evidence and ethical necessity call for action to improve the quality of reporting of harms in RCTs ( 15 , 16 ) . Here , we present a set of recommendations and accompanying explanations for the proper reporting of harms in RCTs . These recommendations should complement the existing CONSORT statement ( Table 2 ) . Examples are presented on the Annals and CONSORT ( www.consort-statement.org ) Web sites . Table 2 . Checklist of Items To Include When Reporting Harms in R and omized , Controlled Trials Recommendations Title and Abstract Recommendation 1 . If the study collected data on harms and benefits , the title or abstract should so state . The title should mention harms if the study of harms was a key trial objective . Many phase I and phase II trials , some phase II/III trials , and most phase IV trials ( 17 , 18 ) target harms as primary outcomes . Yet , the title and abstract seldom contain the word harm . Among 375143 entries in the Cochrane Central Register of Controlled Trials ( Cochrane Library , issue 3 , 2003 ) , search ing titles with the search terms harm or harms yielded 337 references ( compared with 55374 for efficacy and 23415 for safety ) . Of the 337 , excluding several irrelevant articles on self-harm or harm reduction , only 3 trial reports and 2 abstract s contained the word harm in their titles . Authors should present information on harms in the abstract . If no important harms occurred , authors should so state . Explicit reference to the reporting of adverse events in the title or abstract is also important for appropriate data base indexing and information retrieval ( 19 ) . Introduction Background Recommendation 2 . If the trial addresses both harms and benefits , the introduction should so state . The introduction states the scientific background and rationale of an RCT . This requires a balanced presentation whereby the possible benefits of the intervention under investigation are outlined along with the possible harms associated with the treatment . R and omized , controlled trials that focus primarily on harms should clearly state this interest when describing the study objectives in the Introduction and in defining these objectives in the Methods . Methods Outcomes Recommendation 3 . List addressed adverse events with definitions for each ( with attention , when relevant , to grading , expected vs. unexpected events , reference to st and ardized and vali date d definitions , and description of new definitions ) . The Methods section should succinctly define the recorded adverse events ( clinical and laboratory ) . Authors should clarify whether the reported adverse events encompass all the recorded adverse events or a selected sample . They should explain how , why , and who selected adverse events for reporting . In trials that do not mention harms-related data , the Methods section should briefly explain the reason for the omission ( for example , the design did not include the collection of any information on harms ) . Authors should also be explicit about separately reporting anticipated and unexpected adverse events . Expectation may influence the incidence of reported or ascertained adverse events . Making participants aware in the consent form of the possibility of a specific adverse event ( priming ) may increase the reporting rate of the event ( 20 ) . Another example of priming is the finding that the rates of withdrawals due to adverse events and the rates of specific adverse events were significantly higher in trials of aspirin , diclofenac , or indomethacin with comparator drugs compared with placebo-controlled trials ( 21 ) . Presumably , participants were more eager to come forth and report an adverse event or to withdraw from treatment when they knew they could not be receiving inactive placebo . Authors should report whether they used st and ardized and vali date d measurement instruments for adverse events . Several medical fields have developed st and ardized scales ( 22 - 32 ) . Use of nonvali date d scales is common . The source document for well-established definitions and scales should be referenced . New definitions for adverse events should be explicit and clear . Authors should describe how they developed and vali date d new scales . For interventions that target healthy individuals ( for example , many preventive interventions ) , any harm , however minor , may be important to capture and report because the balance of harms and benefits may easily lean toward harms in a low-risk population . For other population s and for interventions that improve major outcomes ( for example , survival ) , severe and life-threatening adverse events may be the only ones that are important in the balance of benefits and harms . Recommendation 4 . Clarify how harms-related information was collected ( mode of data collection , timing , attribution methods , intensity of ascertainment , and harms-related monitoring and stopping rules , if pertinent ) . It is important to describe the question naires , interviews , and tests used to collect information on harms , as well as their timing during follow-up . Passive surveillance of harms leads to fewer recorded adverse events than active surveillance ( 4 ) . Open-ended questions may yield different information , both quantitatively and qualitatively , than structured question naires ( 33 ) . Studies of nonsteroidal , anti-inflammatory drugs ( NSAIDs ) exemplify how data collection methods can affect the detection and reporting of harms . When selective NSAIDs with fewer gastrointestinal adverse events became available , trials reported more than 10 times as many ulcers when comparing these drugs with older NSAIDs as when older NSAIDs were compared with placebo . In the newer trials , more ulcers were detected because participants had regular endoscopy , and the case definition of ulcers was more sensitive ( 34 ) . Authors should specify the time frame of surveillance for adverse events . Some investigators stop recording adverse events at the end of the intervention period or a certain number of days afterward ( for example , 30 days after discontinuation of drug therapy ) and miss events with long latency ( 35 ) . Surgical trials often capture only the adverse events that occur intraoperatively . Several important surgical complications are likely to occur later . Finally , in crossover trials , delayed events might occur while the patient is taking a subsequent assigned treatment . Attribution is the process of deciding whether an adverse event is related to the intervention . Whenever authors filter events through an attribution process , they should state who makes the attribution ( investigators , participants , sponsors , or combinations ) , whether the process is blinded to assigned treatment , and what definitions of adverse events they use ( 4 ) . Discontinuations and withdrawals due to adverse events are especially important because they reflect the ultimate decision of the participant and /or physician to discontinue treatment . Although treatment may occasionally be discontinued for mild or moderate adverse events , attributing discontinuation to a specific reason ( to toxicity , lack of efficacy , other reasons , or combinations of reasons ) may be difficult . For example , in psychopharmacology , dropouts may reflect treatment ineffectiveness as much as toxicity-related intolerance ( 36 ) . Trial reports should specify who gave the reasons for discontinuation ( participants or physicians ) and whether attribution was blinded to the assigned treatment . For example , even in blinded trials , participants and their clinicians are often unblinded before they decide whether to discontinue the intervention . It is important to report participants who are nonadherent or lost to follow-up because their actions may reflect their inability to tolerate the intervention . Moreover , authors should specify how they h and led withdrawals in the analyses of the data . R and omized , controlled trials should report any plan for monitoring for harms and rules for stopping the trial because of harms ( 37 ) . They should clarify whether stopping guidelines examine benefits and harms BACKGROUND Orlistat is a gastrointestinal lipase inhibitor that reduces dietary fat absorption by approximately 30 % , promotes weight loss , and may reduce the risk of developing impaired glucose tolerance and type 2 diabetes in obese subjects . OBJECTIVE To test the hypothesis that orlistat combined with dietary intervention improves glucose tolerance status and prevents worsening of diabetes status more effectively than placebo . METHODS We pooled data from 675 obese ( body mass index , 30 - 43 kg/m2 ) adults at 39 US and Output:

Furthermore , compared with the placebo group , adverse events in the orlistat group were more severe . In the orlistat trials , we identified important disparities in the reporting of adverse events between protocol s , clinical study reports , and published papers . Reports of these trials seemed to have systematic ally understated adverse events .

MS214150

***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 Energy drink consumption has continued to gain in popularity since the 1997 debut of Red Bull , the current leader in the energy drink market . Although energy drinks are targeted to young adult consumers , there has been little research regarding energy drink consumption patterns among college students in the United States . The purpose of this study was to determine energy drink consumption patterns among college students , prevalence and frequency of energy drink use for six situations , namely for insufficient sleep , to increase energy ( in general ) , while study ing , driving long periods of time , drinking with alcohol while partying , and to treat a hangover , and prevalence of adverse side effects and energy drink use dose effects among college energy drink users . Methods Based on the responses from a 32 member college student focus group and a field test , a 19 item survey was used to assess energy drink consumption patterns of 496 r and omly surveyed college students attending a state university in the Central Atlantic region of the United States . Results Fifty one percent of participants ( n = 253 ) reported consuming greater than one energy drink each month in an average month for the current semester ( defined as energy drink user ) . The majority of users consumed energy drinks for insufficient sleep ( 67 % ) , to increase energy ( 65 % ) , and to drink with alcohol while partying ( 54 % ) . The majority of users consumed one energy drink to treat most situations although using three or more was a common practice to drink with alcohol while partying ( 49 % ) . Weekly jolt and crash episodes were experienced by 29 % of users , 22 % reported ever having headaches , and 19 % heart palpitations from consuming energy drinks . There was a significant dose effect only for jolt and crash episodes . Conclusion Using energy drinks is a popular practice among college students for a variety of situations . Although for the majority of situations assessed , users consumed one energy drink with a reported frequency of 1 – 4 days per month , many users consumed three or more when combining with alcohol while partying . Further , side effects from consuming energy drinks are fairly common , and a significant dose effect was found with jolt and crash episodes . Future research should identify if college students recognize the amounts of caffeine that are present in the wide variety of caffeine-containing products that they are consuming , the amounts of caffeine that they are consuming in various situations , and the physical side effects associated with caffeine consumption Objective : Several epidemiologic , longitudinal studies have reported that short sleep duration is a risk factor for the incidence of obesity . However , the vast majority of these studies used self-reported measures of sleep duration and did not examine the role of objective short sleep duration , subjective sleep disturbances and emotional stress . Design : Longitudinal , population -based study .Subjects : We studied a r and om sample of 815 non-obese adults from the Penn State Cohort in the sleep laboratory for one night using polysomnography ( PSG ) and followed them up for a mean of 7.5 years . Subjective and objective measures of sleep as well as emotional stress were obtained at baseline . Obesity was defined as a body mass index ( BMI ) ⩾30 kg/ m-2 . Results : The incidence of obesity was 15 % and it was significantly higher in women and in individuals who reported sleep disturbances , shorter sleep duration and higher emotional stress . Significant mediating effects showed that individuals with subjective sleep disturbances who developed obesity reported the shortest sleep duration and the highest emotional stress , and that subjective sleep disturbances and emotional stress were independent predictors of incident obesity . Further analyses revealed that the association between short sleep duration , subjective sleep disturbances and emotional stress with incident obesity was stronger in young and middle-age adults . Objective short sleep duration was not associated with a significantly increased risk of incident obesity . Conclusion : Self-reported short sleep duration in non-obese individuals at risk of developing obesity is a surrogate marker of emotional stress and subjective sleep disturbances . Objective short sleep duration is not associated with a significant increased risk of incident obesity . The detection and treatment of sleep disturbances and emotional stress should become a target of our preventive strategies against obesity Objective : The authors ' purpose in this study was to determine the sleep patterns of college students to identify problem areas and potential solutions . Participants : A total of 313 students returned completed surveys . Methods : A sleep survey was e-mailed to a r and om sample of students at a North Central university . Questions included individual sleep patterns , problems , and possible influencing factors . Results : Most students reported later bedtimes and rise times on weekends than they did on weekdays . More than 33 % of the students took longer than 30 minutes to fall asleep , and 43 % woke more than once nightly . More than 33 % reported being tired during the day . The authors found no differences between freshmen , sophomores , juniors , seniors , and graduate students for time to fall asleep , number of night wakings , or total time slept each night . Conclusions : Many students have sleep problems that may interfere with daily performance , such as driving and academics . Circadian rhythm management , sleep hygiene , and white noise could ameliorate sleep difficulties STUDY OBJECTIVES To describe the technology use and sleep quality of Americans , and the unique association between technology use and sleep disturbances . METHODS Interviews were conducted via r and om digit dialing ( N = 750 ) or the Internet ( N = 758 ) . 1,508 Americans ( 13 - 64 years old , 50 % males ) matched to 2009 U.S. Census data provided complete interviews . The sample was further divided into adolescents ( 13 - 18 years , N = 171 ) , young adults ( 19 - 29 years , N = 293 ) , middle-aged adults ( 30 - 45 years , N = 469 ) , and older adults ( 46 - 64 years , N = 565 ) to contrast different generations ' technology use . Participants answered a 47-item semi-structured survey , including questions about their sleep habits , and the presence and use of technology in the hour before bed in the past 2 weeks . RESULTS Nine of 10 Americans reported using a technological device in the hour before bed ( e.g. , TVs the most popular ; 60 % ) . However , those under 30 years of age were more likely to use cell phones ( 72 % of adolescents , 67 % of young adults ) than those over 30 years ( 36 % of middle-aged , and 16 % of older adults ) . Young adults ' sleep patterns were significantly later than other age groups on both weekdays and weekend nights . Unlike passive technological devices ( e.g. , TV , mp3 music players ) , the more interactive technological devices ( i.e. , computers/laptops , cell phones , video game consoles ) used in the hour before bed , the more likely difficulties falling asleep ( β = 9.4 , p < 0.0001 ) and unrefreshing sleep ( β = 6.4 , p < 0.04 ) were reported . CONCLUSIONS Technology use near bedtime is extremely prevalent in the United States . Among a range of technologies , interactive technological devices are most strongly associated with sleep complaints Objective : To examine the relationship between body mass index class , presenteeism , and prospect i ve registered sickness absence . Methods : Data were collected from 2983 Belgian workers . Presenteeism was assessed by a single question , evaluating the frequency of being at work , despite illness , during the preceding year . Sickness absence data were registered during 12 months ' follow-up . Multiple logistic regression analysis was conducted . Results : Body mass index class was positively and significantly associated with presenteeism ( at least two occasions of working despite illness ) in the male employees and was a significant predictor of high sickness absence ( at least 10 sick leave days ) in the female population . A final multivariate model demonstrated that these relations were only partly mediated by self-rated health . Conclusion : The results of this study suggest a gender difference concerning absenteeism and presenteeism in overweight and obese employees Background Young adults are at risk for weight gain . Little is known about how to design weight control programs to meet the needs of young adults and few theory-based interventions have been evaluated in a r and omized control trial . The Choosing Healthy Options in College Environments and Setting s ( CHOICES ) study was funded to create a technology-based program for 2-year community college students to help prevent unhealthy weight gain . The purpose of this article is to ( 1 ) provide a brief background on weight-related interventions in young adults ; ( 2 ) describe the study design for the CHOICES study , the conceptual model guiding the research and the CHOICES intervention ; and ( 3 ) discuss implication s of this research for health educators . Translation to Health Education Practice Our experiences from the CHOICES study will be useful in suggesting other theory-based models and intervention strategies that might be helpful in programs attempting to prevent unhealthy weight gain in young adults . In addition , this article discusses important considerations for working with 2-year colleges on this type of health promotion work Context Studies in animals and humans suggest that sleep duration is an important regulator of metabolism . Contribution In this study , 12 young , healthy , normal-weight men exhibited reductions in the satiety hormone leptin , increases in the hunger hormone ghrelin , and increases in hunger after 2 nights of only 4 hours of sleep compared with after 2 nights of 10 hours of sleep . Implication s Inadequate sleep seems to influence the hormones that regulate satiety and hunger in a way that could promote excess eating . The Editors Sleep plays an important role in energy balance . In rodents , food shortage or starvation results in decreased sleep ( 1 ) , and , conversely , total sleep deprivation leads to marked hyperphagia ( 2 ) . Leptin and ghrelin are peripheral signals that contribute to the central regulation of food intake . Leptin , a hormone released by the adipocytes , provides information about energy status to hypothalamic regulatory centers ( 3 ) . In humans , circulating leptin levels rapidly decrease or increase in response to acute caloric shortage or surplus , respectively ( 4 ) . These changes in leptin levels have been associated with reciprocal changes in hunger ( 4 ) . Ghrelin , a peptide produced predominantly by the stomach , is also involved in energy balance regulation , but , in contrast to the anorexigenic effects of leptin , ghrelin stimulates appetite ( 5 ) . It has been proposed that leptin and ghrelin represent the yinyang of one regulatory system that has developed to inform the brain about the current energy balance state ( 6 ) . Over the past 40 years , sleep duration in the U.S. population has decreased by 1 to 2 hours ( 7 - 10 ) . The proportion of young adults sleeping fewer than 7 hours per night has more than doubled between 1960 and 20012002 ( from 15.6 % to 37.1 % ) ( 7 - 10 ) . The effect of sleep curtailment on the control of appetite and food intake is not known . Because of the well-documented associations between sleep and food intake ( 1 , 2 ) , we sought to determine whether sleep duration influences the daytime profiles of leptin and ghrelin . Methods Participants Twelve healthy men(mean age [ SD ] , 22 2 years ] ; mean body mass index [ SD ] , 23.6 2.0 kg/m2 ) who did not smoke or take any medications participated in the study . All of the men were within 10 % of ideal body weight and had regular nocturnal time in bed of 7 to 9 hours . We excluded persons who had traveled across time zones less than 4 weeks before the study . Experimental Protocol The Institutional Review Board of the University of Chicago approved the protocol , and we obtained written informed consent from all participants . During the week preceding each study , we asked participants not to deviate from a fixed time in bed ( 11:00 p.m. to 7:00 a.m. ) by more than 30 minutes . Naps were not allowed . The men participated in 2 studies that were conducted in a r and omized order , were spaced at least 6 weeks apart , and were performed in the Clinical Research Center at the University of Chicago , Chicago , Illinois . Six of the 12 men first performed the study with restricted time in bed , and the remaining 6 men first performed the study with extended time in bed . Average weight did not change over the time period separating the 2 study conditions ( 75.2 kg in the sleep restriction condition vs. 75.4 kg in the sleep extension condition ; P > 0.2 ) . We obtained blood sample s at 20-minute intervals from 8:00 a.m. to 9:00 p.m. after 2 consecutive nights of 10 hours in bed ( 10:00 p.m. to 8:00 a.m. ; sleep extension ) and after 2 consecutive nights of 4 hours in bed ( 1:00 a.m. to 5:00 a.m. ; sleep restriction ) . Sleep was recorded every night . For both extension and restriction conditions , each overnight stay began at 7:00 p.m. with a st and ard hospital dinner , and the first overnight stay ended after breakfast , which was served at 8:00 a.m. We instructed the participants not to deviate from their usual eating habits between breakfast and dinner , but caloric intake was not otherwise monitored . Participants were readmitted in the early evening and , after receiving a st and ard hospital dinner at 7:00 p.m. , remained at bed rest . At 8:00 a.m. after the second night , the participants ' caloric intake was kept constant to avoid meal-related fluctuations of hunger and satiety and consisted of an intravenous glucose infusion at a constant rate of 5 g/kg of body weight every 24 hours . There was no other source of calories . Every hour from 9:00 a.m. to 9:00 p.m. , the men completed vali date d visual analogue scales ( 0 to 10 cm ) for hunger ( 11 ) Output:

The circadian clock is reset in traditional-age college students leading to delayed sleep times . Newly realized autonomy and increased use of technology also prevent traditional-age college students from obtaining sufficient sleep . Insufficient sleep may result in poor academic performance influencing subsequent health outcomes .

MS214151

***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 Unilateral total knee replacement ( TKR ) results in a substantial blood loss and 30 to 50 percent of patients receive allogeneic blood transfusion ( ABT ) . Therefore , the effectiveness of a restrictive transfusion trigger ( hemoglobin [ Hb ] level < 8 g/dL ) plus stimulation of erythropoiesis was evaluated , with or without blood salvage , for reducing ABT in TKR patients . STUDY DESIGN AND METHODS A series of 139 consecutive of primary TKR patients received perioperative iron sucrose ( 2 x 200 mg/48 hr , intravenously [ IV ] ) , plus preoperative erythropoietin ( EPO ; 1 x 40.000 UI , sc ) if preoperative Hb level was less than 130 g per L ( Group A ) . This protocol was applied to another series of 173 consecutive TKR patients who also received postoperative unwashed shed blood ( USB ) if preoperative Hb level was less than 130 g per L ( Group B ) . Perioperative clinical and laboratory data were gathered . RESULTS No adverse effects of iron sucrose , EPO , or USB administration were witnessed , and only 13 patients received ABT overall ( 4 % ) . No major differences in perioperative blood counts or iron metabolism variables were observed between groups , but stimulation of erythropoiesis seemed to be more pronounced in those patients receiving EPO ( p < 0.05 ) . There were no differences in postoperative complications between groups , but length of hospital stay for patients with a preoperative Hb level of less than 130 g per L was shorter in Group B ( p < 0.05 ) . CONCLUSION This blood saving protocol seems to be effective for reducing ABT in TKR patients . Which patients are more likely to benefit from either perioperative iron administration or selective addition of postoperative blood salvage to pharmacologic treatment , however , needs to be further evaluated BACKGROUND The decision to transfuse intra-operatively is based on preoperative haemoglobin ( Hb ) , estimated blood loss and physiological variables . The visual estimate of blood loss is notoriously unreliable especially with small volumes of blood losses in children . OBJECTIVES We sought therefore to determine the appropriateness of intra-operative blood transfusion in a sample of children METHODS All children requiring intra-operative blood transfusion between May and June 2008 were prospect ively studied . Neonates and children already on blood transfusion at induction were excluded . Transfusion was prescribed at the discretion of the attending anaesthetist . The Estimated blood volume ( EBV ) and estimated blood loss (EBL)were determined . Appropriate transfusion was defined as blood transfusion at EBL > 15 % of EBV , maximum allowable blood loss to PCV of 27 % and pre-transfusion Hb < 8g/dl . RESULTS Twenty-five patients were studied with a mean age of 4.16 + /- 3.59 years ( Range 0.33 - 11 years ) . The mean preoperative PCV was 31.14 + /- 3.53 % ( range 25 - 34 % ) . Twelve patients ( 48 % ) were appropriately transfused when MABL was calculated to PCV of 27 % . Nine patients ( 36 % ) had appropriate blood transfusion at an EBL greater or equal to 15 % of the EBV . Of the 12 patients that had pre-transfusion Hb measured , 2 ( 16.6 % ) were appropriately transfused at Hb < 8 g/dl . CONCLUSION The use of near patient monitoring devices should be encouraged as this will give an accurate assessment of Hb and appropriate indication for transfusion . Equipment should be made available to perform gravimetric estimation of blood loss as the visual method is notoriously unreliable BACKGROUND Transfusion thresholds for acute upper gastrointestinal bleeding are controversial . So far , only three small , underpowered studies and one single-centre trial have been done . Findings from the single-centre trial showed reduced mortality with restrictive red blood cell ( RBC ) transfusion . We aim ed to assess whether a multicentre , cluster r and omised trial is a feasible method to substantiate or refute this finding . METHODS In this pragmatic , open-label , cluster r and omised feasibility trial , done in six university hospitals in the UK , we enrolled all patients aged 18 years or older with new presentations of acute upper gastrointestinal bleeding , irrespective of comorbidity , except for exsanguinating haemorrhage . We r and omly assigned hospitals ( 1:1 ) with a computer-generated r and omisation sequence ( r and om permuted block size of 6 , without stratification or matching ) to either a restrictive ( transfusion when haemoglobin concentration fell below 80 g/L ) or liberal ( transfusion when haemoglobin concentration fell below 100 g/L ) RBC transfusion policy . Neither patients nor investigators were masked to treatment allocation . Feasibility outcomes were recruitment rate , protocol adherence , haemoglobin concentration , RBC exposure , selection bias , and information to guide design and economic evaluation of the phase 3 trial . Main exploratory clinical outcomes were further bleeding and mortality at day 28 . We did analyses on all enrolled patients for whom an outcome was available . This trial is registered , IS RCT N85757829 and NCT02105532 . FINDINGS Between Sept 3 , 2012 , and March 1 , 2013 , we enrolled 936 patients across six hospitals ( 403 patients in three hospitals with a restrictive policy and 533 patients in three hospitals with a liberal policy ) . Recruitment rate was significantly higher for the liberal than for the restrictive policy ( 62 % vs 55 % ; p=0·04 ) . Despite some baseline imbalances , Rockall and Blatchford risk scores were identical between policies . Protocol adherence was 96 % ( SD 10 ) in the restrictive policy vs 83 % ( 25 ) in the liberal policy ( difference 14 % ; 95 % CI 7 - 21 ; p=0·005 ) . Mean last recorded haemoglobin concentration was 116 ( SD 24 ) g/L for patients on the restrictive policy and 118 ( 20 ) g/L for those on the liberal policy ( difference -2·0 [ 95 % CI -12·0 to 7·0 ] ; p=0·50 ) . Fewer patients received RBCs on the restrictive policy than on the liberal policy ( restrictive policy 133 [ 33 % ] vs liberal policy 247 [ 46 % ] ; difference -12 % [ 95 % CI -35 to 11 ] ; p=0·23 ) , with fewer RBC units transfused ( mean 1·2 [ SD 2·1 ] vs 1·9 [ 2·8 ] ; difference -0·7 [ -1·6 to 0·3 ] ; p=0·12 ) , although these differences were not significant . We noted no significant difference in clinical outcomes . INTERPRETATION A cluster r and omised design led to rapid recruitment , high protocol adherence , separation in degree of anaemia between groups , and non-significant reduction in RBC transfusion in the restrictive policy . A large cluster r and omised trial to assess the effectiveness of transfusion strategies for acute upper gastrointestinal bleeding is both feasible and essential before clinical practice guidelines change to recommend restrictive transfusion for all patients with acute upper gastrointestinal bleeding . FUNDING NHS Blood and Transplant Research and Development BACKGROUND To determine whether a restrictive strategy of red-cell transfusion and a liberal strategy produced equivalent results in critically ill patients , we compared the rates of death from all causes at 30 days and the severity of organ dysfunction . METHODS We enrolled 838 critically ill patients with euvolemia after initial treatment who had hemoglobin concentrations of less than 9.0 g per deciliter within 72 hours after admission to the intensive care unit and r and omly assigned 418 patients to a restrictive strategy of transfusion , in which red cells were transfused if the hemoglobin concentration dropped below 7.0 g per deciliter and hemoglobin concentrations were maintained at 7.0 to 9.0 g per deciliter , and 420 patients to a liberal strategy , in which transfusions were given when the hemoglobin concentration fell below 10.0 g per deciliter and hemoglobin concentrations were maintained at 10.0 to 12.0 g per deciliter . RESULTS Overall , 30-day mortality was similar in the two groups ( 18.7 percent vs. 23.3 percent , P= 0.11 ) . However , the rates were significantly lower with the restrictive transfusion strategy among patients who were less acutely ill -- those with an Acute Physiology and Chronic Health Evaluation II score of < or = 20 ( 8.7 percent in the restrictive- strategy group and 16.1 percent in the liberal- strategy group ; P=0.03 ) -- and among patients who were less than 55 years of age ( 5.7 percent and 13.0 percent , respectively ; P=0.02 ) , but not among patients with clinical ly significant cardiac disease ( 20.5 percent and 22.9 percent , respectively ; P=0.69 ) . The mortality rate during hospitalization was significantly lower in the restrictive- strategy group ( 22.3 percent vs. 28.1 percent , P=0.05 ) . CONCLUSIONS A restrictive strategy of red-cell transfusion is at least as effective as and possibly superior to a liberal transfusion strategy in critically ill patients , with the possible exception of patients with acute myocardial infa rct ion and unstable angina BACKGROUND Shrinkage of the donor pool coupled with an increasing dem and for blood presents a major challenge to maintaining an adequate blood supply . Consequently it has become even more important to reduce inappropriate blood use , including decisions about when and how much blood to prescribe . This study aim ed to ascertain the levels of inappropriate practice and factors associated with it . STUDY DESIGN AND METHODS The medical records of a r and omly selected sample of hospital patients in Northern Irel and who received a red blood cell transfusion during 2005 ( n = 1474 ) were review ed , and inappropriate transfusion and overtransfusion criteria were applied . Logistic regression models were used to identify factors associated with inappropriate practice and overtransfusion . RESULTS In this study 23 % of transfusions were considered inappropriate , occurring most commonly where the lowest hemoglobin ( Hb ) threshold for transfusion applied . Younger patients , those undergoing surgery , and those with lower comorbidity and higher Hb values were most likely to have an inappropriate transfusion . Among patients appropriately transfused , 19 % were overtransfused . Females and those of lower weight ( < 65 kg ) were most likely to be overtransfused . CONCLUSION While the choice of criteria used to judge decisions will influence the absolute level of inappropriate or overtransfusion reported , our findings suggest that a significant minority of clinicians are either unaware of or are reluctant to accept lower transfusion thresholds . To improve further improve transfusion practice we suggest that barriers to the implementation of recommended transfusion thresholds should be examined and guidance on an appropriate posttransfusion Hb level developed OBJECTIVE To evaluate the effectiveness of prospect i ve review of orders for fresh-frozen plasma ( FFP ) and platelets in reducing blood-product use , and of the effectiveness of preparing pathology residents to serve as clinical consultants . DESIGN At our 572-bed tertiary-care hospital , we developed guidelines for the use of blood products in collaboration with a variety of departments . For patients whose condition(s ) met generally accepted criteria , we identified trigger points to allow for quick release by blood bank staff of blood products . For patients whose condition(s ) did not meet the applicable criteria , the on-call pathology resident review ed the medical record of that patient to determine whether there were any extenuating circumstances ; consulted with the ordering physician and attending pathologist , as needed ; and advised the house staff on appropriate use of blood products . We evaluated the change in use of blood products between the years 2009 and 2012 to assess the effectiveness of the program . RESULTS We observed a decrease of 38.8 % and 31.4 % in the use of FFP and platelets , respectively ( 29.7 % and 21.1 % , respectively , when normalized for the number of discharges ) . If projected to the national level , this improvement would translate to an annual cost reduction of approximately $ 130 million . CONCLUSIONS Prospect i ve review of orders for blood products can significantly improve use of these products , thereby reducing risk to patients and avoiding unnecessary healthcare costs . The involvement of pathology residents in the prospect i ve review process provides an excellent opportunity for their training as laboratory consultants OBJECTIVES To assess the appropriateness of red blood cell ( RBC ) transfusions and the effectiveness of an intervention to reduce inappropriate RBC transfusions . DESIGN Medical record audit by hospital staff using a data form , before and after r and omly allocated interventions ( letter only or letter+visit ) . Criteria for assessing appropriateness of RBC transfusions were based on a systematic literature review . SETTING Ten major urban hospitals in Sydney , New South Wales , in 1998 and 1999 . SUBJECTS Medical records of up to 120 patients at each hospital ( n=1117 ) . INTERVENTIONS Letter-only ( 5 hospitals)-- results of first audit at the hospital mailed to chief executive officer of that hospital ; letter+visit ( 5 hospitals ) results of first audit at the hospital Output:

The overall rates of inappropriate use were 36.7 % ( 95 % CI [ 30.2 , 43.6 ] ) in major cities and 37.5 % ( 95 % CI [ 31.2 , 44.3 ] ) in other cities , respectively ; there was no statistically significant difference ( P > 0.05).In conclusion , China has suffered from a disadvantage in the clinical appropriateness of blood transfusion , especially in plasma and RBC use .

MS214152

***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: UNLABELLED Patients with minimal hepatic encephalopathy ( MHE ) have impaired driving skills , but association of MHE with motor vehicle crashes is unclear . St and ard psychometric tests ( SPT ) or inhibitory control test ( ICT ) can be used to diagnose MHE . The aim was to determine the association of MHE with crashes and traffic violations over the preceding year and on 1-year follow-up . Patients with cirrhosis were diagnosed with MHE by ICT ( MHEICT ) and SPT ( MHESPT ) . Self and department-of-transportation (DOT)-reports were used to determine crashes and violations over the preceding year . Agreement between self and DOT-reports was analyzed . Patients then underwent 1-year follow-up for crash/violation occurrence . Crashes in those with/without MHEICT and MHESPT were compared . 167 patients with cirrhosis had DOT-reports , of which 120 also had self-reports . A significantly higher proportion of MHEICT patients with cirrhosis experienced crashes in the preceding year compared to those without MHE by self-report ( 17 % vs 0.0 % , P = 0.0004 ) and DOT-reports ( 17 % vs 3 % , P = 0.004 , relative risk : 5.77 ) . SPT did not differentiate between those with/without crashes . A significantly higher proportion of patients with crashes had MHEICT compared to MHESPT , both self-reported ( 100 % vs 50 % , P = 0.03 ) and DOT-reported ( 89 % vs 44 % , P = 0.01 ) . There was excellent agreement between self and DOT-reports for crashes and violations ( Kappa 0.90 and 0.80 ) . 109 patients were followed prospect ively . MHEICT patients had a significantly higher future crashes/violations compared to those without ( 22 % vs 7 % , P = 0.03 ) but MHESPT did not . MHEICT ( Odds ratio : 4.51 ) and prior year crash/violation ( Odds ratio : 2.96 ) were significantly associated with future crash/violation occurrence . CONCLUSION Patients with cirrhosis and MHEICT have a significantly higher crash rate over the preceding year and on prospect i ve follow-up compared to patients without MHE . ICT , but not SPT performance is significantly associated with prior and future crashes and violations . There was an excellent agreement between self- and DOT-reports AIM to determine the effect of L-ornithine-L-aspartate ( LOLA ) together with the nutritional improvement and branched chain amino acids ( BCAAs ) substitution , on encephalopathy in liver cirrhosis with malnutrition . METHODS liver cirrhosis patients visited Cipto mangunkusumo Hospital in June-October 2009 were evaluated by critical flicker frequency ( CFF ) test . Encephalopathy is defined when CFF < 39 Hz . Nutritional status is measured by the mid-arm muscle circumference ( MAMC ) and is stated as malnutrition when MAMC < 15 % . All subjects who fulfilled the inclusion criteria received education for adequate calories and protein intake , and then they were be divided into 2 groups by r and omization . One group was given LOLA granules 3 x 6 g/d for 2 weeks , while another group was not . Then their prealbumin and CFF test were measured again . Statistical analysis conducted for this double blind r and omized clinical trial was independent student t test . RESULTS there were 34 liver cirrhosis patients fit the inclusion criteria , and by r and omization 17 subjects were put into group A ( received LOLA ) and 17 subjects into group B ( without LOLA ) . Statistical analysis obtained the statistically significant ( p=0,016 ) of increasing of the mean CFF value in group A ( 2.41 ± 1.6 Hz ) compared to group B ( 0.67 ± 2.3 Hz ) . However , there was not significant increasing of prealbumin level in group A compared to group B ( 1 ± 1.3 mg/dL vs 1.2 ± 1.4 mg/dL , respectively ( p=0,59 ) . Furthermore , after 2 weeks of treatment there was no significant increase of ureum and creatinine level in both groups ( 4 ± 0.5 mg/dL vs 9.3 ± 1.3 mg/dL , ( p=0.4 ) for ureum , -0.1 ( 0.1 ) mg/dL vs 0.1 ± 0.1 mg/dL , ( p=0.3 ) for creatinine . CONCLUSION minimal hepatic encephalopathy with malnutrition can be given a diet of 35 - 40 cal/kgBW and 1.5 g protein/kgBW including BCAA substitution to improve nutritional status , and LOLA granules can be given to improve encephalopathy A representation and interpretation of the area under a receiver operating characteristic ( ROC ) curve obtained by the " rating " method , or by mathematical predictions based on patient characteristics , is presented . It is shown that in such a setting the area represents the probability that a r and omly chosen diseased subject is ( correctly ) rated or ranked with greater suspicion than a r and omly chosen non-diseased subject . Moreover , this probability of a correct ranking is the same quantity that is estimated by the already well-studied nonparametric Wilcoxon statistic . These two relationships are exploited to ( a ) provide rapid closed-form expressions for the approximate magnitude of the sampling variability , i.e. , st and ard error that one uses to accompany the area under a smoothed ROC curve , ( b ) guide in determining the size of the sample required to provide a sufficiently reliable estimate of this area , and ( c ) determine how large sample sizes should be to ensure that one can statistically detect differences in the accuracy of diagnostic techniques BACKGROUND AND AIMS : Minimal hepatic encephalopathy ( MHE ) is associated with poor quality of life and increased work disability in cirrhotic patients . Its prevalence in extrahepatic portal vein obstruction ( EHPVO ) is not known . We studied the prevalence of MHE in EHPVO patients and utility of critical flicker frequency ( CFF ) for diagnosing MHE . PATIENTS AND METHODS : Thirty-four EHPVO patients with a history of variceal bleed ( age 23.2 ± 11.2 yr , M : F 22:12 ) diagnosed by either Doppler US or MR angiography , which demonstrated portal vein obstruction and /or portal vein cavernoma , were evaluated by psychometry ( number connection tests A , B or figure connection tests A , B ) and P300 auditory event-related potential ( P300ERP ) . CFF was also evaluated . MHE was diagnosed by abnormal psychometry ( > 2 st and ard deviation [ SD ] ) and /or P300ERP ( > 2.5 SD ) . RESULTS : Prevalence of MHE ( N = 12 ) was 35.3 % . Of 34 patients , P300ERP was abnormal ( 380.0 ± 28.9 msec ) in 11 ( 32 % ) , psychometry in 9 ( 26.4 % ) , both P300ERP and psychometry in 8 ( 23.5 % ) , and CFF < 38 Hz in 7 ( 21 % ) patients . Six ( 67 % ) patients with abnormal psychometry and 7 ( 64 % ) with abnormal P300ERP had CFF below 38 Hz . CFF had sensitivity ( 75 % ) , specificity ( 96 % ) , positive predictive value ( 86 % ) , negative predictive value ( 93 % ) , and diagnosis accuracy of 91 % when compared to patients with both abnormal psychometry and P300ERP . The venous ammonia level was higher in patients with MHE ( 83.1 ± 29.7 vs 44.7 ± 16.1 μmol/L , P < 0.001 ) compared to patients without MHE . Spontaneous shunts were present in 67 % of patients with MHE compared to 14 % of non-MHE patients . MHE was more common in patients with spontaneous shunts ( 72.7 % vs 17.4 % , P= 0.001 ) than without spontaneous shunts . CONCLUSIONS : Prevalence of MHE in EHPVO patients is 35.3 % , and CFF alone can reliably diagnose 88 % of MHE patients with both abnormal psychometry and P300ERP . However , in view of the relatively low number of patients with MHE , the usefulness of CFF in this setting awaits confirmatory studies UNLABELLED The diagnosis of hepatic encephalopathy ( HE ) relies on clinical , neurophysiological , psychometric and laboratory variables . The relationships between such tests remain debated . The aim of this study was to determine the laboratory correlates/prognostic value of neurophysiological/psychometric abnormalities in patients with cirrhosis . Seventy-two patients and 14 healthy volunteers underwent EEG and paper- and -pencil psychometry ( PHES ) . Blood was obtained for C reactive protein ( CRP ) , interleukin 6 ( IL6 ) , tumor necrosis factor (TNF)α , ammonia and indole/oxindole . Patients were followed prospect ively for a median of 22 months in relation to the occurrence of death , transplantation and HE-related hospitalizations . Thirty-three patients had normal PHES and EEG , 6 had abnormal PHES , 18 abnormal EEG and 13 abnormal PHES and EEG . Patients with abnormal PHES had higher CRP ( 17 ± 22 vs 7 ± 6 , P < 0.01 ) , IL6 ( 32 ± 54 vs 12 ± 13 , P < 0.05 ) and TNFα ( 17 ± 8 vs 11 ± 7 , P < 0.001 ) levels than those with normal PHES . Patients with abnormal EEG had higher indole ( 430 ± 270 vs 258 ± 255 , P < 0.01 ) and ammonia ( 66 ± 35 vs 45 ± 27 , P < 0.05 ) levels than those with normal EEG . Psychometric test scores showed significant correlations with CRP , TNFα and IL6 ; EEG indices with ammonia and IL6 . CRP and TNFα concentrations were independent predictors of abnormal PHES , ammonia and indole of abnormal EEG on multivariate analysis . Seven patients were lost to follow-up ; of the remaining 65 , 20 died and 14 underwent transplantation ; 15 developed HE requiring hospitalization . PHES and EEG performance were independent predictors of HE and death ( P < 0.05 ) . CONCLUSION PHES and EEG abnormalities in patients with cirrhosis have partially different biochemical correlates and independently predict outcome OBJECTIVES : Cirrhotics with minimal hepatic encephalopathy ( MHE ) have a poor health-related quality of life ( HRQOL ) . Treatment of MHE is still evolving . The aim of this double-blind r and omized pilot study was to assess the efficacy of rifaximin in improving neuropsychometric ( NP ) test performance and HRQOL in patients with MHE . METHODS : MHE was diagnosed if any two NP tests ( number and figure connection tests , picture completion , digit symbol , and block design tests ) were deranged beyond 2 s.d . of normal . HRQOL was assessed using the sickness impact profile ( SIP ) question naire . RESULTS : A total of 486 patients with cirrhosis were screened and 284 were found eligible . Out of these 115 ( 40.9 % ) had MHE , of which 21 refused consent and 94 were r and omized to receive placebo ( n=45 ) and rifaximin ( n=49 ; 1200 mg/day ) for 8 weeks . At the end of treatment , significantly more number of patients in rifaximin group showed reversal of MHE ( 75.5 % ( 37/49 ) vs. 20 % ( 9/45 ) in placebo group ; P < 0.0001 ) . Rifaximin group also showed significant reduction in mean number of abnormal NP tests ( baseline , 2.35 ( 95 % confidence interval ( CI ) , 2.17–2.53 ) ; 2 weeks , 1.29 ( 95 % CI , 1.02–1.56 ) , P=0.002 ; 8 weeks , 0.81 ( 95 % CI , 0.61–1.02 ) , P=0.000 ) , compared with placebo group ( baseline , 2.31 ( 95 % CI , 2.03–2.59 ) ; 2 weeks , 2.03 ( 95 % CI , 1.74–2.31 ) ; 8 weeks , 1.97 ( 95 % CI , 1.69–2.25 ) , P>0.05 ) . The mean total SIP score also improved significantly in rifaximin group ( baseline , 11.67 ( 95 % CI , 10.31–13.03 ) ; 8 weeks , 6.45 ( 95 % CI , 5.59–7.30 ) ; P=0.000 ) compared with placebo group ( baseline , 9.86 ( 95 % CI , 8.66–11.06 ) ; 8 weeks , 8.51 ( 95 % CI , Output:

Critical Flicker Frequency has a high specificity and moderate sensitivity for diagnosing minimal hepatic encephalopathy .

MS214153

***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 effectiveness of liver preservation solutions remains in evidence . Cold ischemia time , steatosis , exp and ed criterion donors , operational cost , and survival represent important roles in its success . In a prospect i ve cohort study between August 2009 and April 2014 , 178 patients were allocated into an Institut Georges Lopez - 1 ( IGL-1 ) solution group ( 63.5 % ) or histidine-tryptophan-ketoglutarate ( HTK ) group ( 36.5 % ) . There were no differences among recipient 's characteristics including age , skin color , gender , Model for End-stage Liver Disease score , acute rejection , cholestasis , and reperfusion syndrome incidences . Also , donors , age average , skin color , donor risk index , time in intensive care unit , hemodynamic variables , infections , and steatosis incidences were similar . The average cold ischemia time was 494 minutes in the IGL-1 group and 489 minutes in the HTK group ( P = .77 ) . Alanine aminotransferase and aspartate aminotransferase serum levels on the first postoperative day were 707 and 1185 mg/dL , respectively , with IGL-1 and 1298 and 2291 mg/dL , respectively , with HTK ( P = .016 ) and similar at day 15 ( P > .88 ) . The incidence of delayed graft function was 4.5 % with IGL-1 and 4.6 % with HTK ( P = .90 ) . The incidence primary nonfunction was 2.7 % with IGL-1 and 3.1 % with HTK ( P = .71 ) . The incidence of perioperative death was 11.5 % with IGL-1 and 13.8 % with HTK ( P = .94 ) . The survival in 30 months was 86 % in IGL-1 group and 82 % in HTK group ( P = .66 ) . Both preservation solutions are efficient to liver transplantations with deceased donors . Major prospect i ve trials are necessary to evaluate each preservation solution 's particularities . The preservation solution availability in each transplantation center must guide its use at the present moment 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 ALTHOUGH University of Wisconsin ( UW ) solution remains the most commonly used for all intrabdominal organs , Celsior solution , widely utilized in clinical setting for the preservation of intrathoracic organs , has been recently proposed as a cold-storage solution for abdominal organs . One of the reasons for focusing on abdominal preservation with Celsior is to proceed with one solution for the preservation of all organs . Experimental studies have shown excellent results in kidney , liver , and tissue preservation in alternative to the U W. Celsior , due to its peculiar physical properties ( osmotic pressure ) , is able to limit the edema that develops rapidly after cold ischemia and able to prevent free-radical mediated tissue injury by its biochemical characteristics . Its clinical use in these organs is now under investigation in different centers . The only report about Celsior solution for human liver preservation experiences in a small , uncontrolled series , and the study suggested that this solution is appropriate for clinical use in liver preservation . A prospect i ve , r and omized , multicenter open clinical trial was instituted to compare preservation properties of the two solutions in liver transplantation , and a detailed report of the completed study will be made at a later date . This preliminary report contains the data collected from a single center to prove the equivalence of both solutions with regard to initial functioning and short and long-term graft and patient survival BACKGROUND To test the effectiveness of a simpler surgical technique for cadaveric liver procurement for liver transplantation , a prospect i ve r and omized study was carried out between August 1994 and December 1995 , to compare aortic perfusion only ( APO ) for flush-preservation of the liver with the conventional combined aortic and portal perfusion ( APP ) technique . METHODS Forty multiple organ donors were enrolled with 20 in each arm of the trial . Donor parameters ( age , bodyweight , liver function tests ) , surgeons performing the operations , the involvement of other procurement teams and the total ischaemic times were similar in the two groups . The liver recipients had a wide range of native liver pathology but were of similar age , sex and bodyweight in the two groups . RESULTS The mean procurement operation times for the APO and APP groups were 126.7+/-38.6 and 137.8+/-55.9 min , respectively ( P = ns ) . The perfusion took longer to complete in the APO group ( 10.2+/-1.7 vs 7.2+/-1.4 min ( APP ) , P < 0.001 ) . The liver temperature fell to its lowest level ( 12.5+/-3.4 degrees C ( APO ) vs 11+/-3 degrees C ( APP ) , P = ns ) in a similar time ( 11.9+/-3.8 min ( APO ) vs 9.3+/-3.4 mins ( APP ) , P = ns ) . There was no graft primary non-function or graft arterial injury in either group . There was no significant difference between the APO and APP initial graft outcomes . The 3-month patient survival rate was identical in the two groups ( 95 % ) ; 81 % of renal grafts from the APO donors functioned well from the time of transplantation as did 76 % of those from APP donors . CONCLUSIONS It is concluded that the APO procurement technique produces equivalent results to those achieved with the APP method . The simplicity of the APO technique makes it the preferred technique University of Wisconsin ( UW ) solution has been the st and ard for preservation of liver transplantation grafts since 1989 . However , some studies demonstrated that histidine-tryptophan-ketoglutarate ( HTK ) solution is also effective . The purpose of this study was to compare the efficacy of both solutions in liver transplantation . From January 2003 to August 2004 the livers of deceased donors were r and omized into HTK and UW groups . The 102 studied patients included 65 ( 63.7 % ) in the UW group and 37 ( 36.3 % ) in the HTK group . Sex , race , hemodynamic state , use of adrenergic drugs , and presence of steatosis in the donor were similarly distributed in the two groups ( P > .05 ) . The mean age of the donors was 38.1 years ( SD + /-14.4 ) in the UW group and 44.6 years ( SD + /-14.2 ) in the HTK cohort ( P = .036 ) . Sex , race , age , etiology of the cirrhosis , retransplant , acute liver failure , portal thrombosis , and Child-Pugh and MELD scores in the recipients were similarly distributed in the two recipient sample s ( P > .05 ) . Among 89 patients who completed 4 months of follow-up , the HTK group included eight cases ( 25.8 % ) of biliary complications versus five cases ( 8.6 % ) in the UW group ( P = .033 ; OR = 2.0 95 % CI = 1.2 - 3.5 ) . The incidence of graft dysfunction was 2.8 % in the HTK group and 9.4 % in the UW group ( P = .15 ) . In conclusion , UW and HTK solutions were equally effective for the preservation of the hepatic graft . The routine use of HTK solution can reduce the costs of liver transplantation Background Celsior solution ( CS ) is a high-sodium , low-potassium , low-viscosity extracellular solution that has been used for liver graft preservation in recent years , although experience with it is still limited . We performed an open-label r and omized active-controlled trial comparing CS with the University of Wisconsin solution ( UW ) for liver transplantation ( LT ) , with a follow-up period of 5 years . Methods Adult transplant recipients ( n = 102 ) were prospect ively r and omized to receive either CS ( n = 51 ) or UW ( n = 51 ) . The two groups were comparable with respect to donor and recipient characteristics . The primary outcome measure was the incidence of postreperfusion syndrome ( PRS ) . Secondary outcome measures included primary nonfunction ( PNF ) or primary dysfunction ( PDF ) , liver retransplantation , and graft and patient survival . Other secondary outcome measures were days in the intensive care unit ( ICU ) and the rates of acute rejection , chronic rejection , infectious complications , postoperative reoperations , and vascular and biliary complications . Results In all , 14 posttransplant variables revealed no significant differences between the groups . There were no cases of PNF or PDF . The incidence of PRS was 5.9 % in the CS group and 21.6 % in the UW group ( P = 0.041 ) . After reperfusion , CS revealed greater control of serum potassium ( P = 0.015 ) , magnesium levels ( P = 0.005 ) , and plasma glucose ( P = 0.042 ) than UW . Respective patient survivals at 3 , 12 , and 60 months were 95.7 , 87.2 , and 82.0 % for the CS group and 95.7 , 83.3 , and 66.6 % for the UW group ( P = 0.123 ) . Conclusions While retaining the same degree of safety and effectiveness as UW for LT , CS may yield postliver graft reperfusion benefits , as shown in this study by a significant reduction in the incidence of PRS and greater metabolic control University of Wisconsin solution ( UWS ) is the gold st and ard for graft preservation . Celsior solution ( CS ) is a new solution not as yet widely used in liver grafts . The aim of this study was to compare the liver function of transplanted grafts stored in these 2 preservation solutions . The primary endpoints were the rates of primary nonfunction ( PNF ) and primary dysfunction ( PDF ) . We performed a prospect i ve and pseudor and omized study that included 196 patients ( representing 104 and 92 livers preserved in UWS and CS , respectively ) at La Fe University Hospital ( Valencia , Spain ) between March 2003 and May 2005 . PNF and PDF rates , liver function laboratory parameters , postoperative bleeding , vascular and biliary complications , and patient and graft survival at 3 years were compared for the 2 groups . The 2 groups were similar in terms of donor variables , recipient variables , and surgical techniques . The PNF rates were 2.2 % and 1.9 % in the CS and UWS groups , respectively ( P = not significant ) , and the PDF rates were 15.2 % and 15.5 % in the CS and UWS groups , respectively ( P = not significant ) . There were no significant differences in the laboratory parameters for the 2 groups , except for alanine aminotransferase levels in month 3 , which were lower in the CS group ( P = 0.01 ) . No significant differences were observed in terms of complications . Three-year patient and graft survival rates were as follows for years 1 , 2 , and 3 : 83 % , 80 % , and 76 % ( patient ) and 80 % , 77 % , and 73 % ( graft ) for the UWS group and 83 % , 77 % , and 70 % ( patient ) and 81 % , 73 % , and 67 % ( graft ) for the CS group ( P = not significant ) . In conclusion , this study shows that CS is as effective as UWS in liver preservation Primary dysfunction ( PDF ) still occurs after orthotopic liver transplantation ( OLT ) . Celsior solution ( CS ) might offer some advantages over the conventional University of Wisconsin ( UW ) solution for organ preservation , but to date , this has not been prospect ively evaluated in the context of OLT . In this prospect i ve , r and omized , multicenter , pilot study , 215 potential liver donors were enrolled and r and omized . In 42 cases , the livers were unsuitable for transplantation ; therefore , 173 r and omized livers ultimately were implanted after perfusion and cold preservation with CS ( n = 83 ) or UW solution ( n = 90 ) . In accord with the indications of the CS manufacturing company , total CS infusion volume was 90 mL/kg , greater than that of UW solution ( 60 mL/kg ) . The main aim of the study is to compare the prevalence of PDF between the two groups . Donor and recipient variables were similar in the two groups . Episodes of PDF were numerically lower in the CS ( 2.4 % ) than UW group ( 7.8 % ) , but the difference was not statistically significant . There was a trend toward a lesser need for early re-OLT ( < 30 days ) in the CS group ( P = .0507 ) , but again , no statistically significant difference emerged . Overall and time-differentiated postoperative deaths also were similar . One-year actuarial patient ( UW , 89 % v CS , 87 % ) and graft ( UW , 83 % v CS , 85 % ) survival rates were similar . In conclusion , CS was similar to UW solution as a preservation solution in the clinical setting of OLT at the infusion volumes described , although some theoretical advantages of CS composition suggest that CS might prove a valid alternative to UW preservation solution in multiorgan harvesting , including the liver . A study on a larger patient basis is needed BACKGROUND Institut Georges Lopez-1 Output:

In conclusion , there is no significant evidence that aortic-only perfusion of the DBD liver compromises transplantation outcomes , and it may be favored because of its simplicity . However , there is currently insufficient evidence to advocate for the use of any particular perfusion/preservation fluid over the others .

MS214154

***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 effectiveness of an exercise intervention for people in early and midstage Parkinson 's disease ( stages 2 and 3 of Hoehn and Yahr ) in improving spinal flexibility and physical performance in a sample of community-dwelling older people is described . DESIGN AND SETTING Fifty-one men and women , aged 55 - 84 years , identified through advertisement , local support groups , and local neurologists were enrolled into a r and omized , controlled trial . Subjects were assigned r and omly to an intervention or a usual care arm ( i.e. , no specific exercise ) . Of the original 51 participants , 46 completed the r and omized , controlled trial . Participants in the exercise arm ( n = 23 ) received individual instruction three times per week for 10 weeks . Participants in the usual care arm ( n = 23 ) were " wait listed " for intervention . MEASUREMENTS Changes over 10 weeks in spinal flexibility ( i.e. , functional axial rotation ) and physical performance ( i.e. , functional reach , timed supine to st and ) were the primary outcome measures . RESULTS MANOVA conducted for the three primary outcome variables demonstrated significant differences ( P < or = .05 ) between the two groups . Further analysis using ANOVA demonstrated significant differences between groups in functional axial rotation and functional reach for the intervention compared with the control group . There was no significant difference in supine to sit time . CONCLUSION Study results demonstrate that improvements in axial mobility and physical performance can be achieved with a 10-week exercise program for people in the early and midstages of PD The impact of dyskinesias and motor fluctuations on quality of life ( QOL ) at various stages in the course of Parkinson 's disease ( PD ) is not well understood . In 301 subjects with early PD enrolled in a clinical trial ( CALM-PD ) , we quantified the impact of motor complications on QOL and investigated how this changes over time . We also compared QOL related to demographic and treatment characteristics . The presence of dyskinesias was associated with visual analogue scale ( VAS ) scores 3.0 of 100 points higher ( better ) than those without dyskinesias in years 1 to 2 , even when adjusting for Unified Parkinson 's Disease Rating Scale ( UPDRS ) motor scores . The positive association between dyskinesias and QOL scores was more marked in older patients . In years 3 to 4 , dyskinesias no longer had a significant relationship with QOL . Younger subjects had higher VAS scores . Gender , motor fluctuations , and treatment regimen had no significant association with QOL , although a trend was found toward a small negative effect of motor fluctuations on QOL . We conclude that motor complications that occur within the first 4 years of treatment of PD do not have a significant negative effect on quality of life as measured by a visual analogue scale for most patients AIM To investigate the effects of an aerobic training in subjects with Parkinson 's disease ( PD ) as compared to a medical Chinese exercise ( Qigong ) . METHODS DESIGN r and omized controlled trial with a cross over design . SETTING PD out- patients referred to a Neurorehabilitation facility for the management of motor disability . SUBJECTS 26 PD patients in Hoehn and Yahr stage II to III under stable medication were r and omly allocated to either Group AT1+QG2 ( receiving 20 aerobic training sessions followed by 20 ' ' Qigong ' ' group sessions with 2 month interval between the interventions ) , or Group QG1+AT2 ( performing the same treatments with an inverted sequence ) . MAIN OUTCOME MEASURES clinical effects of treatment were sought through the Unified Parkinson 's Disease Rating Scale ( UPDRS ) , Brown 's Disability Scale ( B'DS ) , six-Minute Walking Test ( 6MWT ) , Borg scale for breathlessness , Beck Depression Inventory ( BDI ) and Parkinson 's Disease Question naire-39 items ( PDQ-39 ) . A spirometry test and maximum cardiopulmonary exercise test ( CPET ) were also performed to determine the pulmonary function , the metabolic and cardio-respiratory requests at rest and under exercise . All measures were taken immediately before and at the completion of each treatment phase . RESULTS The statistical analysis focusing on the evolution of motor disability and quality of life revealed a significant interaction effect between group and time for the 6MWT ( time x group effect : F : 5.4 P=0.002 ) and the Borg scale ( time x group effect : F : 4.2 P=0.009 ) . Post hoc analysis showed a significant increase in 6MWT and a larger decrease in Borg score after aerobic training within each subgroup , whereas no significant changes were observed during Qigong . No significant changes over time were detected through the analysis of UPDRS , B'DS , BDI and PDQ-39 scores . The analysis of cardiorespiratory parameters showed significant interaction effects between group and time for the Double Productpeak ( time x group effect : F : 7.7 P=0.0003 ) , the VO(2peak ) ( time x group effect : F : 4.8 P=0.007 ) , and the VO(2)/kg ratio ( time x group effect : F : 4.3 P=0.009 ) , owing to their decrease after aerobic training to an extent that was never observed after Qigong treatment . CONCLUSIONS Aerobic training exerts a significant impact on the ability of moderately disabled PD patients to cope with exercise , although it does not improve their self-sufficiency and quality of life Objective : To detect the effectiveness of incremental speed-dependent treadmill training on postural instability , dynamic balance and fear of falling in patients with idiopathic Parkinson 's disease . Design : R and omized controlled trial . Setting : Ankara Education and Research Hospital , 2nd PM&R Clinic , Cardiopulmonary Rehabilitation Unit . Subjects : Fifty-four patients with idiopathic Parkinson 's disease in stage 2 or 3 of the Hoehn Yahr staging entered , and 31 patients ( 21 training , 10 control ) had outcome data . Interventions : Postural instability of patients with Parkinson 's disease was assessed using the motor component of the Unified Parkinson 's Disease Rating Scale ( UPDRS ) , Berg Balance Test , Dynamic Gait Index and Falls Efficacy Scale . Twenty-one patients with Parkinson 's disease participated in an eight-week exercise programme using incremental speed-dependent treadmill training . Before and after the training programme , balance , gait , fear of falling and walking distance and speed on treadmill were assessed in both Parkinson 's disease groups . Main measures : Walking distance and speed on treadmill , UPDRS , Berg Balance Test , Dynamic Gait Index and Falls Efficacy Scale . Results : Initial total walking distance of the training group on treadmill was 266.45 ± 82.14 m and this was progressively increased to 726.36 ± 93.1 m after 16 training session ( P < 0.001 ) . Tolerated maximum speed of the training group on treadmill at baseline was 1.9 ± 0.75 km/h and improved to 2.61 ± 0.77 km/h ( P < 0.001 ) . Berg Balance Test , Dynamic Gait Index and Falls Efficacy Scale scores of the training group were improved significantly after the training programme ( P < 0.01 ) . There was no significant improvement in any of the outcome measurements in the control group ( P > 0.05 ) . Conclusions : Specific exercise programmes using incremental speed-dependent treadmill training may improve mobility , reduce postural instability and fear of falling in patients with Parkinson 's disease The purpose of this study was to determine if individuals with Parkinson 's disease ( PD ) who completed an 8-week , supervised PoleStriding exercise program would undergo significant improvements in cognitive skills , activities of daily living , motor function , and quality of life . The Unified Parkinson 's Disease Rating Scale ( UPDRS ) and the Parkinson 's Disease Question naire ( PDQ-39 ) were used to measure functional independence . Six male volunteers ( 72.7+/-3.7 years of age ) performed PoleStriding exercise three times per week for 37+/-3 minutes . Differences in the participants ' pre- and post-training scores on the UPDRS and PDQ-39 were analyzed using the Wilcoxin Signed Ranks Test . A statistically significant improvement occurred in the UPDRS ( P<0.026 ) and PDQ-39 ( P<0.028 ) scores following the moderate-intensity exercise intervention . The results of this nonr and omized clinical trial indicate that an 8-week individualized PoleStriding exercise program increases perceived functional independence and quality of life in individuals with PD The aim of our study was to evaluate the influence of low-intensity exercise on levodopa absorption and levodopa motor effect . We studied the pharmacokinetics and pharmacodynamics of levodopa under resting conditions and under a workload of 50 watts for 2 hours on a cycle ergometer in 12 parkinsonian patients with predictable fluctuations of motor disability . The patients attended the hospital on both days in a provoked off state . After a baseline assessment of motor disability using the Columbia University rating scale ( CURS scale ) and a blood test for measurement of the baseline levodopa concentration in the plasma , 100 mg levodopa and 25 mg benserazide were administered as a single dose orally . Blood sample s for measurement of the levodopa concentration in the plasma were taken , and motor assessment s were conducted at 15-minute intervals for 240 minutes and at 30-minute intervals from 240 to 360 minutes . All patients were able to perform the exercise program . The baseline Columbia University rating scale score did not differ significantly between both days . The mean levodopa concentration in plasma at half-maximal motor effect tended to be higher during exercise and indicated that the patients needed a higher levodopa concentration in plasma to achieve the half-maximal motor effect . The maximal levodopa concentration in plasma tended to be higher with exercise . Both trends did not reach statistical significance . In summary , there was not a negative or a positive net effect of exercise on pharmacokinetics and pharmacodynamics of levodopa . However , there were two counteracting trends : a trend toward better levodopa absorption and a trend toward a deteriorated concentration-effect correlation Objective : To determine whether the Alex and er Technique , alongside normal treatment , is of benefit to people disabled by idiopathic Parkinson 's disease . Design : A r and omized controlled trial with three groups , one receiving lessons in the Alex and er Technique , another receiving massage and one with no additional intervention . Measures were taken pre and post-intervention , and at follow-up , six months later . Setting : The Polyclinic at the University of Westminster , Central London . Subjects : Ninety-three people with clinical ly confirmed idiopathic Parkinson 's disease . Interventions : The Alex and er Technique group received 24 lessons in the Alex and er Technique and the massage group received 24 sessions of massage . Main outcome measures : The main outcome measures were the Self- assessment Parkinson 's Disease Disability Scale ( SPDDS ) at best and at worst times of day . Secondary measures included the Beck Depression Inventory and an Attitudes to Self Scale . Results : The Alex and er Technique group improved compared with the no additional intervention group , pre-intervention to post-intervention , both on the SPDDS at best , p = 0.04 ( confidence interval ( CI ) –6.4 to 0.0 ) and on the SPDDS at worst , p = 0.01 ( CI –11.5 to –1.8 ) . The comparative improvement was maintained at six-month follow-up : on the SPDDS at best , p = 0.04 ( CI –7.7 to 0.0 ) and on the SPDDS at worst , p = 0.01 ( CI –11.8 to –0.9 ) . The Alex and er Technique group was comparatively less depressed post-intervention , p = 0.03 ( CI –3.8 to 0.0 ) on the Beck Depression Inventory , and at six-month follow-up had improved on the Attitudes to Self Scale , p = 0.04 ( CI –13.9 to 0.0 ) . Conclusions : There is evidence that lessons in the Alex and er Technique are likely to lead to sustained benefit for people with Parkinson 's disease Background and Purpose . The application of motor imagery practice in the treatment of Parkinson ’s disease ( PD ) is a novel treatment approach for improving motor function . The purpose of this study was to compare group treatment using a combination of physical and motor imagery practice with group treatment using only physical practice in subjects with PD . Methods . Of 23 patients with idiopathic PD , 12 received combined therapy , whereas 11 received physical therapy alone . Exercises for both groups were applied during 1-h sessions held twice a week for 12 weeks . Comparable motor tasks provided to both groups included callisthenic exercises , functional tasks , and relaxation exercises . However , the experimental group was treated with both imagery and real practice , whereas the control group received only physical exercises . Outcome measures included the time required to complete sequences of movements , the performance of balance tasks , impairment and functional scores on the Unified Parkinson ’s Disease Rating Scale ( UPDRS ) , and specific cognitive abilities ( Stroop and clock drawing tests ) . Results . Following the intervention , the combined treatment group exhibited significantly faster performance of movement sequences than the control group . In addition , the experimental subjects demonstrated higher gains in the mental and motor subsets of the UPDRS and in the cognitive tests . Both groups improved on the activities of daily living scale . Conclusions . The combination of motor imagery and real practice may be effective in the treatment of PD , especially for reducing bradykinesia . The implementation of this treatment regimen allows for the extension of practice time with negligible risk and low cost INTRODUCTION Frequent falls and risk of injury are evident in individuals with Parkinson 's disease ( PD ) Output:

RESULTS Within the Body Structure and Function category , there was moderate evidence that exercise result ed in improvements in postural instability . Within the Activity category , there was moderate evidence that exercise was effective for improving balance task performance . In contrast , within the Participation category , there was limited evidence that exercise result ed in improvements in QOL measures or fall events . DISCUSSION AND CONCLUSIONS Regardless of the strength of the evidence , the studies review ed all report that exercise result ed in improvements in postural stability and balance task performance .

MS214155

***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: To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrolment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results OBJECTIVES We sought to document the pregnancy and neurodevelopmental outcome in monochorionic diamniotic twin pregnancies and to identify risk factors for death and impairment . STUDY DESIGN We conducted a prospect i ve cohort study of 136 monochorionic twins followed up from the first trimester until infancy . RESULTS A total of 122 ( 90 % ) pregnancies result ed in 2 survivors , 6 ( 4 % ) in 1 survivor and 8 ( 6 % ) in no survivor . In all , 230 ( 92 % ) of 250 surviving infants were assessed at a mean age of 24 months . Neurodevelopmental impairment was present in 22 ( 10 % ) infants . Death or impairment of 1 or both infants occurred in 28 ( 22 % ) of 126 pregnancies . Twin-to-twin transfusion syndrome and assisted conception increased the risk of both death and impairment , whereas early-onset discordant growth only increased the risk of death . CONCLUSION The mortality in this prospect i ve series was 8 % and neurodevelopmental impairment occurred in 10 % of infants After the adoption of the use of umbilical artery and middle cerebral artery peak systolic velocity in high-risk pregnancies and in pregnancies that are at risk of having an anemic fetus , the main focus of Doppler ultrasonography in obstetrics today is intrauterine growth-restricted fetuses . What is most needed at this time are ( 1 ) training of sonographers and sonologists on how to perform a Doppler study , ( 2 ) an international classification of intrauterine growth-restricted fetuses , and ( 3 ) a study of the natural history of intrauterine growth-restricted fetuses that might contribute to a better underst and ing of the intrauterine growth-restriction process and to st and ard treatment of intrauterine growth-restricted fetuses . Future investigations , which would include r and omized studies , could be design ed from the results of such studies We have done a r and omised controlled trial to assess the effect on primary management and outcome of routine doppler ultrasound examinations of the umbilical and uterine arteries during pregnancy . Over 9 months , 2600 women with singleton pregnancies were recruited from a general obstetric population . Of 2475 women who delivered in hospital after 20 weeks ' gestation , 1246 had been allocated at r and om to receive st and ard antenatal care with routine doppler examinations . The first doppler ultrasound was done at 19 - 22 weeks ' gestation , and thereafter examinations were monthly if the pregnancy was considered high risk ( 192 ) or once at 32 weeks if considered low risk ( 1054 ) . The control group of 1229 women received st and ard , antenatal care without doppler ultrasonography . The study groups did not differ in number of antenatal admissions or cardiotocographs , gestational age at delivery , method of delivery , frequency of deliveries with fetal distress , or need for resuscitation or admission to the neonatal intensive care unit . More perinatal deaths occurred in the doppler group ( 17 vs 7 , relative risk 2.4 , 95 % Cl 1.00 - 5.76 ) , but only 1 of 11 normally formed stillbirths and none of the 4 normally formed neonatal deaths after 24 weeks ' gestation had an abnormal umbilical-artery doppler examination . We did not demonstrate any improvement in neonatal outcome by routine doppler ultrasound screening of a general obstetric population One-hundred and eighty-seven single pregnancies , at full term determined accurately and confirmed by ultrasound before 17 weeks of amenorrhea and which were proceeding normally were monitored every 2 days after the expected end of term . This was done by conventional methods and in 132 cases by determining a placental resistance index ( R = D/S ) . All the deliveries were carried out under monitoring and the infants examined by a pediatrician . The umbilical index at 280 to 300 days of gestation was found to be constant and equal to R = 0.52 + /- 0.041 ( n + /- D ) and the signs of fetal distress and post-maturity increased beyond term . In the first 80 pregnancies studies in this way , the determination of the value of the index R was not included in the decision-making process . Twelve of the 14 cases of fetal heart rate arrhythmia during delivery and all recorded cases of post-mature clinical signs and neonatal acidosis occurred when the index was above RI = 0.54 . The next 107 pregnancies were r and omly divided into two groups . In the 52 pregnancies in which the Doppler revealed an index at two consecutive determinations in excess of 0.54 , this was taken to be a criterion for the induction of childbirth . In this group , some of the women gave birth earlier , without any increase in the number of Caesareans and this result ed in fewer post-mature infants . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND No consensus exists for the best way to monitor and when to trigger delivery in mothers of babies with fetal growth restriction . We aim ed to assess whether changes in the fetal ductus venosus Doppler waveform ( DV ) could be used as indications for delivery instead of cardiotocography short-term variation ( STV ) . METHODS In this prospect i ve , European multicentre , unblinded , r and omised study , we included women with singleton fetuses at 26 - 32 weeks of gestation who had very preterm fetal growth restriction ( ie , low abdominal circumference [ < 10th percentile ] and a high umbilical artery Doppler pulsatility index [ > 95th percentile ] ) . We r and omly allocated women 1:1:1 , with r and omly sized blocks and stratified by participating centre and gestational age ( < 29 weeks vs ≥29 weeks ) , to three timing of delivery plans , which differed according to antenatal monitoring strategies : reduced cardiotocograph fetal heart rate STV ( CTG STV ) , early DV changes ( pulsatility index > 95th percentile ; DV p95 ) , or late DV changes ( A wave [ the deflection within the venous waveform signifying atrial contraction ] at or below baseline ; DV no A ) . The primary outcome was survival without cerebral palsy or neurosensory impairment , or a Bayley III developmental score of less than 85 , at 2 years of age . We assessed outcomes in surviving infants with known outcomes at 2 years . We did an intention to treat study for all participants for whom we had data . Safety outcomes were deaths in utero and neonatal deaths and were assessed in all r and omly allocated women . This study is registered with IS RCT N , number 56204499 . FINDINGS Between Jan 1 , 2005 and Oct 1 , 2010 , 503 of 542 eligible women were r and omly allocated to monitoring groups ( 166 to CTG STV , 167 to DV p95 , and 170 to DV no A ) . The median gestational age at delivery was 30·7 weeks ( IQR 29·1 - 32·1 ) and mean birthweight was 1019 g ( SD 322 ) . The proportion of infants surviving without neuroimpairment did not differ between the CTG STV ( 111 [ 77 % ] of 144 infants with known outcome ) , DV p95 ( 119 [ 84 % ] of 142 ) , and DV no A ( 133 [ 85 % ] of 157 ) groups ( ptrend=0·09 ) . 12 fetuses ( 2 % ) died in utero and 27 ( 6 % ) neonatal deaths occurred . Of survivors , more infants where women were r and omly assigned to delivery according to late ductus changes ( 133 [ 95 % ] of 140 , 95 % , 95 % CI 90 - 98 ) were free of neuroimpairment when compared with those r and omly assigned to CTG ( 111 [ 85 % ] of 131 , 95 % CI 78 - 90 ; p=0.005 ) , but this was accompanied by a non-significant increase in perinatal and infant mortality . INTERPRETATION Although the difference in the proportion of infants surviving without neuroimpairment was non-significant at the primary endpoint , timing of delivery based on the study protocol using late changes in the DV waveform might produce an improvement in developmental outcomes at 2 years of age . FUNDING ZonMw , The Netherl and s and Dr Hans Ludwig Geisenhofer Foundation , Germany OBJECTIVE To identify the temporal sequence of abnormal Doppler changes in the fetal circulation in a subset of early and severely growth-restricted fetuses . METHODS This was a prospect i ve observational study in a tertiary care/teaching hospital . Twenty-six women who were diagnosed with growth-restricted fetuses by local st and ards before 32 weeks ' gestation and who had abnormal uterine and umbilical artery Doppler velocimetry were enrolled onto the study . To compare Doppler changes as a function of time , pulsed-wave Doppler ultrasound was performed on five vessels in the fetal peripheral and central circulations . Doppler examinations were performed twice-weekly and on the day of delivery if the fetal heart rate tracing became abnormal . Doppler indices were scored as abnormal when their values were outside the local reference limits on two or more consecutive measurements . Biometry for assessment of fetal growth was performed every 2 weeks . Computerized fetal heart rates were obtained daily . Delivery was based on a non-reactive fetal heart rate tracing and not on Doppler information . Patients with a severely growth-restricted fetus who were delivered for maternal indications such as pre-eclampsia were excluded . Perinatal outcome endpoints included : intrauterine death , gestational age at delivery , newborn weight , central nervous system damage of grade 2 or greater , intraventricular hemorrhage and neonatal mortality . RESULTS Mean gestational age and newborn weight at delivery were 29 ( st and ard deviation ( SD ) , 2 ) weeks and 818 ( SD , 150 ) g , respectively . The sequence of Doppler velocimetric changes was described by onset time cumulative curves that showed two time-related events . First , for each vessel there was a progressive increase in the percent of fetuses developing a Doppler abnormality . Second , severely growth-restricted fetuses followed a progressive sequence of acquiring Doppler abnormalities which were categorized into ' early ' and ' late ' Doppler changes . Early changes occurred in peripheral vessels ( umbilical and middle cerebral arteries ; 50 % of patients affected 15 - 16 days prior to delivery ) . Late changes included umbilical artery reverse flow , and abnormal changes in the ductus venosus , aortic and pulmonary outflow tracts ( 50 % of patients affected 4 - 5 days prior to delivery ) . The time interval between the occurrence of early and late changes was significantly different ( P < 0.0001 ) and late changes were significantly associated with perinatal death ( P < 0.01 ) . CONCLUSIONS Doppler velocimetry abnormalities develop in different vessels of the severely growth-restricted fetus in a sequential fashion . Late changes in vascular adaptation by the severely growth-restricted fetus are the best predictor of perinatal death Abstract Despite widespread application of ultrasound imaging and Doppler blood flow studies , the effects of their frequent and repeated use in pregnancy have not been evaluated in controlled trials . From 2834 women with single pregnancies at 16 - 20 weeks gestation , 1415 were selected at r and om to receive ultrasound imaging and continuous-wave Doppler flow studies at 18 , 24 , 28 , 34 , and 38 weeks gestation ( the intensive group ) and 1419 to receive single ultrasound imaging at 18 weeks ( the regular group ) . Outcome data was obtained from 99 % of women who entered the study . The only difference between the two groups was significantly higher intrauterine growth restriction in the intensive group , when expressed both as Output:

Data for serious neonatal morbidity were not pooled due to high heterogeneity between the three studies that reported it ( 1098 babies ) ( evidence grade d very low).The use of Doppler to evaluate early and late changes in ductus venosus in early fetal growth restriction was not associated with significant differences in any perinatal death after r and omisation . However , there was an improvement in long-term neurological outcome in the cohort of babies in whom the trigger for delivery was either late changes in ductus venosus or abnormalities seen on computerised CTG . Current evidence suggests that the use of Doppler ultrasound on the umbilical artery in high-risk pregnancies reduces the risk of perinatal deaths and may result in fewer obstetric interventions .

MS214156

***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 Blockade of programmed death 1 ( PD-1 ) , an inhibitory receptor expressed by T cells , can overcome immune resistance . We assessed the antitumor activity and safety of BMS-936558 , an antibody that specifically blocks PD-1 . METHODS We enrolled patients with advanced melanoma , non-small-cell lung cancer , castration-resistant prostate cancer , or renal-cell or colorectal cancer to receive anti-PD-1 antibody at a dose of 0.1 to 10.0 mg per kilogram of body weight every 2 weeks . Response was assessed after each 8-week treatment cycle . Patients received up to 12 cycles until disease progression or a complete response occurred . RESULTS A total of 296 patients received treatment through February 24 , 2012 . Grade 3 or 4 drug-related adverse events occurred in 14 % of patients ; there were three deaths from pulmonary toxicity . No maximum tolerated dose was defined . Adverse events consistent with immune-related causes were observed . Among 236 patients in whom response could be evaluated , objective responses ( complete or partial responses ) were observed in those with non-small-cell lung cancer , melanoma , or renal-cell cancer . Cumulative response rates ( all doses ) were 18 % among patients with non-small-cell lung cancer ( 14 of 76 patients ) , 28 % among patients with melanoma ( 26 of 94 patients ) , and 27 % among patients with renal-cell cancer ( 9 of 33 patients ) . Responses were durable ; 20 of 31 responses lasted 1 year or more in patients with 1 year or more of follow-up . To assess the role of intratumoral PD-1 lig and ( PD-L1 ) expression in the modulation of the PD-1-PD-L1 pathway , immunohistochemical analysis was performed on pretreatment tumor specimens obtained from 42 patients . Of 17 patients with PD-L1-negative tumors , none had an objective response ; 9 of 25 patients ( 36 % ) with PD-L1-positive tumors had an objective response ( P=0.006 ) . CONCLUSIONS Anti-PD-1 antibody produced objective responses in approximately one in four to one in five patients with non-small-cell lung cancer , melanoma , or renal-cell cancer ; the adverse-event profile does not appear to preclude its use . Preliminary data suggest a relationship between PD-L1 expression on tumor cells and objective response . ( Funded by Bristol-Myers Squibb and others ; Clinical Trials.gov number , NCT00730639 . ) BACKGROUND Ipilimumab is an approved treatment for patients with advanced melanoma . We aim ed to assess ipilimumab as adjuvant therapy for patients with completely resected stage III melanoma at high risk of recurrence . METHODS We did a double-blind , phase 3 trial in patients with stage III cutaneous melanoma ( excluding lymph node metastasis ≤1 mm or in-transit metastasis ) with adequate resection of lymph nodes ( ie , the primary cutaneous melanoma must have been completely excised with adequate surgical margins ) who had not received previous systemic therapy for melanoma from 91 hospitals located in 19 countries . Patients were r and omly assigned ( 1:1 ) , central ly by an interactive voice response system , to receive intravenous infusions of 10 mg/kg ipilimumab or placebo every 3 weeks for four doses , then every 3 months for up to 3 years . Using a minimisation technique , r and omisation was stratified by disease stage and geographical region . The primary endpoint was recurrence-free survival , assessed by an independent review committee , and analysed by intention to treat . Enrollment is complete but the study is ongoing for follow-up for analysis of secondary endpoints . This trial is registered with EudraCT , number 2007 - 001974 - 10 , and Clinical Trials.gov , number NCT00636168 . FINDINGS Between July 10 , 2008 , and Aug 1 , 2011 , 951 patients were r and omly assigned to ipilimumab ( n=475 ) or placebo ( n=476 ) , all of whom were included in the intention-to-treat analyses . At a median follow-up of 2·74 years ( IQR 2·28 - 3·22 ) , there were 528 recurrence-free survival events ( 234 in the ipilimumab group vs 294 in the placebo group ) . Median recurrence-free survival was 26·1 months ( 95 % CI 19·3 - 39·3 ) in the ipilimumab group versus 17·1 months ( 95 % CI 13·4 - 21·6 ) in the placebo group ( hazard ratio 0·75 ; 95 % CI 0·64 - 0·90 ; p=0·0013 ) ; 3-year recurrence-free survival was 46·5 % ( 95 % CI 41·5 - 51·3 ) in the ipilimumab group versus 34·8 % ( 30·1 - 39·5 ) in the placebo group . The most common grade 3 - 4 immune-related adverse events in the ipilimumab group were gastrointestinal ( 75 [ 16 % ] vs four [ < 1 % ] in the placebo group ) , hepatic ( 50 [ 11 % ] vs one [ < 1 % ] ) , and endocrine ( 40 [ 8 % ] vs none ) . Adverse events led to discontinuation of treatment in 245 ( 52 % ) of 471 patients who started ipilimumab ( 182 [ 39 % ] during the initial treatment period of four doses ) . Five patients ( 1 % ) died due to drug-related adverse events . Five ( 1 % ) participants died because of drug-related adverse events in the ipilimumab group ; three patients died because of colitis ( two with gastrointestinal perforation ) , one patient because of myocarditis , and one patient because of multiorgan failure with Guillain-Barré syndrome . INTERPRETATION Adjuvant ipilimumab significantly improved recurrence-free survival for patients with completely resected high-risk stage III melanoma . The adverse event profile was consistent with that observed in advanced melanoma , but at higher incidences in particular for endocrinopathies . The risk-benefit ratio of adjuvant ipilimumab at this dose and schedule requires additional assessment based on distant metastasis-free survival and overall survival endpoints to define its definitive value . FUNDING Bristol-Myers Squibb BACKGROUND Limited evidence exists to show that adding a third agent to platinum-doublet chemotherapy improves efficacy in the first-line advanced non-small-cell lung cancer ( NSCLC ) setting . The anti-PD-1 antibody pembrolizumab has shown efficacy as monotherapy in patients with advanced NSCLC and has a non-overlapping toxicity profile with chemotherapy . We assessed whether the addition of pembrolizumab to platinum-doublet chemotherapy improves efficacy in patients with advanced non-squamous NSCLC . METHODS In this r and omised , open-label , phase 2 cohort of a multicohort study ( KEYNOTE-021 ) , patients were enrolled at 26 medical centres in the USA and Taiwan . Patients with chemotherapy-naive , stage IIIB or IV , non-squamous NSCLC without targetable EGFR or ALK genetic aberrations were r and omly assigned ( 1:1 ) in blocks of four stratified by PD-L1 tumour proportion score ( < 1 % vs ≥1 % ) using an interactive voice-response system to 4 cycles of pembrolizumab 200 mg plus carboplatin area under curve 5 mg/mL per min and pemetrexed 500 mg/m2 every 3 weeks followed by pembrolizumab for 24 months and indefinite pemetrexed maintenance therapy or to 4 cycles of carboplatin and pemetrexed alone followed by indefinite pemetrexed maintenance therapy . The primary endpoint was the proportion of patients who achieved an objective response , defined as the percentage of patients with radiologically confirmed complete or partial response according to Response Evaluation Criteria in Solid Tumors version 1.1 assessed by masked , independent central review , in the intention-to-treat population , defined as all patients who were allocated to study treatment . Significance threshold was p<0·025 ( one sided ) . Safety was assessed in the as-treated population , defined as all patients who received at least one dose of the assigned study treatment . This trial , which is closed for enrolment but continuing for follow-up , is registered with Clinical Trials.gov , number NCT02039674 . FINDINGS Between Nov 25 , 2014 , and Jan 25 , 2016 , 123 patients were enrolled ; 60 were r and omly assigned to the pembrolizumab plus chemotherapy group and 63 to the chemotherapy alone group . 33 ( 55 % ; 95 % CI 42 - 68 ) of 60 patients in the pembrolizumab plus chemotherapy group achieved an objective response compared with 18 ( 29 % ; 18 - 41 ) of 63 patients in the chemotherapy alone group ( estimated treatment difference 26 % [ 95 % CI 9 - 42 % ] ; p=0·0016 ) . The incidence of grade 3 or worse treatment-related adverse events was similar between groups ( 23 [ 39 % ] of 59 patients in the pembrolizumab plus chemotherapy group and 16 [ 26 % ] of 62 in the chemotherapy alone group ) . The most common grade 3 or worse treatment-related adverse events in the pembrolizumab plus chemotherapy group were anaemia ( seven [ 12 % ] of 59 ) and decreased neutrophil count ( three [ 5 % ] ) ; an additional six events each occurred in two ( 3 % ) for acute kidney injury , decreased lymphocyte count , fatigue , neutropenia , and sepsis , and thrombocytopenia . In the chemotherapy alone group , the most common grade 3 or worse events were anaemia ( nine [ 15 % ] of 62 ) and decreased neutrophil count , pancytopenia , and thrombocytopenia ( two [ 3 % ] each ) . One ( 2 % ) of 59 patients in the pembrolizumab plus chemotherapy group experienced treatment-related death because of sepsis compared with two ( 3 % ) of 62 patients in the chemotherapy group : one because of sepsis and one because of pancytopenia . INTERPRETATION Combination of pembrolizumab , carboplatin , and pemetrexed could be an effective and tolerable first-line treatment option for patients with advanced non-squamous NSCLC . This finding is being further explored in an ongoing international , r and omised , double-blind , phase 3 study . FUNDING Merck & BACKGROUND This phase II study evaluated the safety and activity of ipilimumab , a fully human mAb that blocks cytotoxic T-lymphocyte antigen-4 , in patients with advanced melanoma . PATIENTS AND METHODS Patients with previously treated , unresectable stage III/stage IV melanoma received 10 mg/kg ipilimumab every 3 weeks for four cycles ( induction ) followed by maintenance therapy every 3 months . The primary end point was best overall response rate ( BORR ) using modified World Health Organization ( WHO ) criteria . We also carried out an exploratory analysis of proposed immune-related response criteria ( irRC ) . RESULTS BORR was 5.8 % with a disease control rate ( DCR ) of 27 % ( N = 155 ) . One- and 2-year survival rates ( 95 % confidence interval ) were 47.2 % ( 39.5 % to 55.1 % ) and 32.8 % ( 25.4 % to 40.5 % ) , respectively , with a median overall survival of 10.2 months ( 7.6 - 16.3 ) . Of 43 patients with disease progression by modified WHO criteria , 12 had disease control by irRC ( 8 % of all treated patients ) , result ing in a total DCR of 35 % . Adverse events ( AEs ) were largely immune related , occurring mainly in the skin and gastrointestinal tract , with 19 % grade 3 and 3.2 % grade 4 . Immune-related AEs were manageable and generally reversible with corticosteroids . CONCLUSION Ipilimumab demonstrated clinical activity with encouraging long-term survival in a previously treated advanced melanoma population BACKGROUND Ipilimumab , an anti-CTLA4 monoclonal antibody , demonstrated survival benefit in melanoma with immune-related ( ir ) adverse events ( irAEs ) managed by the protocol -defined guidelines . This phase 2 study evaluated ipilimumab+paclitaxel (Taxol)/carboplatin in extensive-disease-small-cell lung cancer ( ED-SCLC ) . DESIGN Patients ( n=130 ) with chemotherapy-naïve ED-SCLC were r and omized 1 : 1 : 1 to receive paclitaxel ( 175 mg/m2)/carboplatin ( area under the curve=6 ) with either placebo ( control ) or ipilimumab 10 mg/kg in two alternative regimens , concurrent ipilimumab ( ipilimumab+paclitaxel/carboplatin Output:

Conclusion The cytotoxic T-lymphocyte-associated protein-4 ( CTLA-4 ) inhibitors have a significantly higher risk of FAE ( P=0.01 ) , whereas programmed cell death protein 1 ( PD-1 ) inhibitors were not . The most common CTLA-4-related FAE was gastrointestinal toxicity , and the most common PD-1-related FAE was pulmonary toxicity . Moreover , we have shown that ipilimumab has significant dose-dependent lethal toxicity

MS214157

***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: Learning of a procedural motor-skill task is known to progress through a series of unique memory stages . Performance initially improves during training , and continues to improve , without further rehearsal , across subsequent periods of sleep . Here , we investigate how this delayed sleep-dependent learning is affected when the task characteristics are varied across several degrees of difficulty , and whether this improvement differentially enhances individual transitions of the motor-sequence pattern being learned . We report that subjects show similar overnight improvements in speed whether learning a five-element unimanual sequence ( 17.7 % improvement ) , a nine-element unimanual sequence ( 20.2 % ) , or a five-element bimanual sequence ( 17.5 % ) , but show markedly increased overnight improvement ( 28.9 % ) with a nine-element bimanual sequence . In addition , individual transitions within the motor-sequence pattern that appeared most difficult at the end of training showed a significant 17.8 % increase in speed overnight , whereas those transitions that were performed most rapidly at the end of training showed only a non-significant 1.4 % improvement . Together , these findings suggest that the sleep-dependent learning process selectively provides maximum benefit to motor-skill procedures that proved to be most difficult prior to sleep OBJECTIVE To study the associations between sleep quality /quantity and performance in auditory/visual working memory tasks of different load levels . METHOD Sixty schoolchildren aged 6 to 13 years from normal school classes voluntarily participated . Actigraphy measurement was done during a typical school week for 72 consecutive hours . It was timed together with the working memory experiments to obtain information on children 's sleep during that period . The n-back task paradigm was used to examine auditory and visual working memory functions . RESULTS Lower sleep efficiency and longer sleep latency were associated with a higher percentage of incorrect responses in working memory tasks at all memory load levels ( partial correlations , controlling for age , all p values < .05 , except in visual 0-back and auditive 2-back tasks ) ; shorter sleep duration was associated with performing tasks at the highest load level only ( partial correlations , controlling for age , p < .05 ) . Also in general linear models ( controlling for age , gender , and socioeconomic status ) , sleep efficiency ( F = 11.706 , p = .050 ) and latency ( F = 3.588 , p = .034 ) were significantly associated with the mean incorrect response rate in auditory working memory tasks . CONCLUSIONS Sleep quality and quantity affect performance of working memory tasks in school-age children . In children with learning difficulties the possibility of underlying sleep problems should be excluded The endogenous circadian oscillator in mammals , situated in the suprachiasmatic nuclei , receives environmental photic input from specialized subsets of photoreceptive retinal ganglion cells . The human circadian pacemaker is exquisitely sensitive to ocular light exposure , even in some people who are otherwise totally blind . The magnitude of the re setting response to white light depends on the timing , intensity , duration , number and pattern of exposures . We report here that the circadian re setting response in humans , as measured by the pineal melatonin rhythm , is also wavelength dependent . Exposure to 6.5 h of monochromatic light at 460 nm induces a two-fold greater circadian phase delay than 6.5 h of 555 nm monochromatic light of equal photon density . Similarly , 460 nm monochromatic light causes twice the amount of melatonin suppression compared to 555 nm monochromatic light , and is dependent on the duration of exposure in addition to wavelength . These studies demonstrate that the peak of sensitivity of the human circadian pacemaker to light is blue-shifted relative to the three-cone visual photopic system , the sensitivity of which peaks at approximately 555 nm . Thus photopic lux , the st and ard unit of illuminance , is inappropriate when quantifying the photic drive required to reset the human circadian pacemaker BACKGROUND No prospect i ve studies exist on the relationship between sleep problems early in life and subsequent alcohol use . Stimulated by the adult literature linking sleep problems to the subsequent onset of alcohol use disorders in some adults , we examined whether sleep problems in early childhood predicted the onset of alcohol and other drug use in adolescence and whether such a relationship was mediated by other known predictors of this relationship , namely , attention problems , anxiety/depression , and aggression in late childhood . METHODS This study is part of an ongoing longitudinal study of the development of risk for alcohol and other substance use disorders . Study participants were 257 boys from a community-recruited sample of high-risk families . RESULTS Mothers ' ratings of their children 's sleep problems at ages 3 to 5 years significantly predicted an early onset of any use of alcohol , marijuana , and illicit drugs , as well as an early onset of occasional or regular use of cigarettes by age 12 to 14 . Additionally , although sleep problems in early childhood also predicted attention problems and anxiety/depression in later childhood , these problems did not mediate the relationship between sleep problems and onset of alcohol and other drug use . CONCLUSIONS This is , to our knowledge , the first study that prospect ively examines the relationship between sleep problems and early onset of alcohol use , a marker of increased risk for later alcohol problems and alcohol use disorders . Moreover , early childhood sleep problems seem to be a robust marker for use of drugs other than alcohol . Implication s for the prevention of early alcohol and other drug use are discussed OBJECTIVE To investigate the relationship between the presence of a television set , a gaming computer , and /or an Internet connection in the room of adolescents and television viewing , computer game playing , and Internet use on the one h and , and time to bed , time up , time spent in bed , and overall tiredness in first- and fourth-year secondary -school children on the other h and . METHODS A r and om sample of students from 15 schools in Fl and ers , Belgium , yielded 2546 children who completed a question naire with questions about media presence in bedrooms ; volume of television viewing , computer game playing , and Internet use ; time to bed and time up on average weekdays and average weekend days ; and questions regarding the level of tiredness in the morning , at school , after a day at school , and after the weekend . RESULTS Children with a television set in their rooms went to bed significantly later on weekdays and weekend days and got up significantly later on weekend days . Overall , they spent less time in bed on weekdays . Children with a gaming computer in their rooms went to bed significantly later on weekdays . On weekdays , they spent significantly less time in bed . Children who watched more television went to bed later on weekdays and weekend days and got up later on weekend days . They spent less time in bed on weekdays . They reported higher overall levels of being tired . Children who spent more time playing computer games went to bed later on weekdays and weekend days and got up later on weekend days . On weekdays , they actually got up significantly earlier . They spent less time in bed on weekdays and reported higher levels of tiredness . Children who spent more time using the Internet went to bed significantly later during the week and during the weekend . They got up later on weekend days . They spent less time in bed during the week and reported higher levels of tiredness . Going out was also significantly related to sleeping later and less . CONCLUSION Concerns about media use should not be limited to television . Computer game playing and Internet use are related to sleep behavior as well . Leisure activities that are unstructured seem to be negatively related to good sleep patterns . Imposing more structure ( eg , end times ) might reduce impact Output:

Rates of change were negative across age , sex and day type categories , but varied according to region , with Europe , the USA , Canada and Asia showing decreases and Australia , the UK and Sc and inavia showing increases . Over the last 103 years , there have been consistent rapid declines in the sleep duration of children and adolescents

MS214158

***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: CONTEXT The section of a research article most likely to be read is the abstract , and therefore it is particularly important that the abstract reflect the article faithfully . OBJECTIVE To assess abstract s accompanying research articles published in 6 medical journals with respect to whether data in the abstract could be verified in the article itself . DESIGN Analysis of simple r and om sample s of 44 articles and their accompanying abstract s published during 1 year(July 1 , 1996-June 30 , 1997 ) in each of 5 major general medical journals ( Annals of Internal Medicine , BMJ , JAMA , Lancet , and New Engl and Journal of Medicine ) and a consecutive sample of 44 articles published during 15 months ( July 1 , 1996-August 15 , 1997 ) in the CMAJ . MAIN OUTCOME MEASURE Abstract s were considered deficient if they contained data that were either inconsistent with corresponding data in the article 's body ( including tables and figures ) or not found in the body at all . RESULTS The proportion of deficient abstract s varied widely ( 18%-68 % ) and to a statistically significant degree ( P<.001 ) among the 6 journals studied . CONCLUSIONS Data in the abstract that are inconsistent with or absent from the article 's body are common , even in large-circulation general medical journals OBJECTIVE . Our aim was to compare 2 laxatives , namely , polyethylene glycol 3350 without electrolytes and milk of magnesia , evaluating the efficacy , safety , acceptance , and 1-year outcomes . METHODS . Seventy-nine children with chronic constipation and fecal incontinence were assigned r and omly to receive polyethylene glycol or milk of magnesia and were treated for 12 months in tertiary care pediatric clinics . Children were counted as improved or recovered depending on resolution of constipation , fecal incontinence , and abdominal pain after 1 , 3 , 6 , and 12 months . An intent-to-treat analysis was used . Safety was assessed with evaluation of clinical adverse effects and blood tests . RESULTS . Thirty-nine children were assigned r and omly to receive polyethylene glycol and 40 to receive milk of magnesia . At each follow-up visit , significant improvement was seen in both groups , with significant increases in the frequency of bowel movements , decreases in the frequency of incontinence episodes , and resolution of abdominal pain . Compliance rates were 95 % for polyethylene glycol and 65 % for milk of magnesia . After 12 months , 62 % of polyethylene glycol-treated children and 43 % of milk of magnesia-treated children exhibited improvement , and 33 % of polyethylene glycol-treated children and 23 % of milk of magnesia-treated children had recovered . Polyethylene glycol and milk of magnesia did not cause clinical ly significant side effects or blood abnormalities , except that 1 child was allergic to polyethylene glycol . CONCLUSIONS . In this r and omized study , polyethylene glycol and milk of magnesia were equally effective in the long-term treatment of children with constipation and fecal incontinence . Polyethylene glycol was safe for the long-term treatment of these children and was better accepted by the children than milk of magnesia Background Chronic constipation represents a common problem in children . The treatment of functional constipation is challenging . Some studies have investigated the effect of prokinetic agents as potential therapies for motility disorders of the lower gastrointestinal tract with paradoxical results . The present study aim ed to investigate the effect of oral domperidone in the treatment of chronic functional constipation in children . Method A total of 105 children with chronic functional constipation ( according to Rome III criteria ) who were referred to the Pediatric Gastroenterology Clinic were recruited in this double-blind r and omized clinical trial . The study subjects were r and omly divided into two groups , the first of which received polyethylene glycol ( PEG ) solution 0.6 g/kg/day two times a day for 6 months and domperidone syrup 0.15 mL/kg three times a day for 3 months ( case group ) while the second one received PEG with the same dose for 6 months and placebo for 3 months with the same dose ( control group ) . The two groups were compared regarding their symptoms and Rome III criteria through 1 , 3 , and 6 months following therapy . Primary outcome was response to treatment , and a response was defined as decrease in signs and symptoms that did not fulfill Rome III criteria . Secondary outcome measures were side effects during the course of treatment . Results A significant difference was observed both before and after PEG and domperidone treatment and before and after PEG and placebo treatment regarding Rome III criteria . There was no significant difference in response to treatment between the two study groups during 1 ( p = 1 ) , 3 ( p = 0.799 ) , and 6 ( p = 0.403 ) month follow up periods . Also , the two groups were not significantly different regarding the Rome III criteria during the mentioned follow up periods . There were no side effects during the course of treatment . Conclusion There was no additional effect of domperidone as adjunct to PEG in the treatment of children with constipation Background : Recently , polyethylene glycol ( PEG 3350 ) has been suggested as a good alternative laxative to lactulose as a treatment option in paediatric constipation . However , no large r and omised controlled trials exist evaluating the efficacy of either laxative . Aims : To compare PEG 3350 ( Transipeg : polyethylene glycol with electrolytes ) with lactulose in paediatric constipation and evaluate clinical efficacy/side effects . Patients : One hundred patients ( aged 6 months–15 years ) with paediatric constipation were included in an eight week double blinded , r and omised , controlled trial . Methods : After faecal disimpaction , patients < 6 years of age received PEG 3350 ( 2.95 g/sachet ) or lactulose ( 6 g/sachet ) while children ⩾6 years started with 2 sachets/day . Primary outcome measures were : defecation and encopresis frequency/week and successful treatment after eight weeks . Success was defined as a defecation frequency ⩾3/week and encopresis ⩽1 every two weeks . Secondary outcome measures were side effects after eight weeks of treatment . Results : A total of 91 patients ( 49 male ) completed the study . A significant increase in defecation frequency ( PEG 3350 : 3 pre v 7 post treatment/week ; lactulose : 3 pre v 6 post/week ) and a significant decrease in encopresis frequency ( PEG 3350 : 10 pre v 3 post/week ; lactulose : 8 pre v 3 post/week ) was found in both groups ( NS ) . However , success was significantly higher in the PEG group ( 56 % ) compared with the lactulose group ( 29 % ) . PEG 3350 patients reported less abdominal pain , straining , and pain at defecation than children using lactulose . However , bad taste was reported significantly more often in the PEG group . Conclusions : PEG 3350 ( 0.26 ( 0.11 ) g/kg ) , compared with lactulose ( 0.66 ( 0.32 ) g/kg ) , provided a higher success rate with fewer side effects . PEG 3350 should be the laxative of first choice in childhood constipation OBJECTIVE To investigate the efficacy and safety of polyethylene glycol ( PEG ) 3350 in the treatment of childhood fecal impaction . METHODS This was a prospect i ve , double-blind , parallel , r and omized study of 4 doses of PEG 3350 ; 0.25 g/kg per day , 0.5 g/kg per day , 1 g/kg per day , 1.5 g/kg per day , given for 3 days in children with constipation for > 3 months and evidence of fecal impaction . RESULTS Forty patients completed the study ( 27 boys , median age 7.5 , range 3.3 - 13.1 years ) . Disimpaction occurred in 75 % of children , with a significant difference between the two higher doses and the lower doses ( 95 % vs 55 % , P < .005 ) . All groups had an increased number of bowel movements during the 5-day study versus baseline , respectively : 6.5 versus 1.1 ( P < .005 ) , 8.0 versus 1.3 ( P < .005 ) , 10.9 versus 1.7 ( P < .005 ) , and 12.3 versus 1.4 ( P < .005 ) . Adverse effects included nausea ( 5 % ) , vomiting ( 5 % ) , bloating ( 18 % ) , cramping ( 5 % ) , and diarrhea ( 13 % ) . Diarrhea and bloating were more prevalent ( P < .02 ) in the higher-dose than in the lower-dose group . No clinical ly significant changes in electrolytes were noted . CONCLUSIONS The 3-day administration of PEG 3350 is safe and effective in the treatment of childhood fecal impaction at doses of 1 and 1.5 g/kg per day Background : Polyethylene glycol ( PEG ) is often considered as the first-line treatment for functional constipation in children . Descurainia sophia ( L. ) Webb et Berth ( D. sophia ) is a safe recommended medicine in Iranian folk and Traditional Persian Medicine for the treatment of constipation . Objectives : To clinical ly compare D. sophia with PEG 4000 ( without electrolyte ) in pediatric constipation and to assess its efficacy and side effects . Patients and Methods : 120 patients aged 2 - 12 years with constipation for at least 3 months were included in an 8 weeks lasting r and omized controlled trial within two parallel-groups . Children received either PEG , 0.4 g/kg/day , or D. sophia seeds , 2 grams ( for children aged 2 - 4 years ) and 3 grams ( for those aged > 4 years ) per day . Results : A total of 109 patients completed the study ( 56 in D. sophia and 53 in PEG group ) . At the end of the study , 36 ( 64.3 % ) patients in D. sophia group and 29 ( 54.7 % ) in PEG group were out of Rome III criteria ( P = 0.205 ) . Median weekly stool frequency in 0 , 1 , 2 , 3 weeks of the treatment was found to be 2 , 5 , 5 , 5 in D. sophia and 3 , 4 , 4 , 5 in PEG group ( P = 0.139 , 0.076 , 0.844 , 0.294 ) , respectively . The number of patients who suffered flatulence was less ( 5 , 8.9 % ) in D. sophia group as compared to PEG group ( 6 , 11.3 % ) at the end of the trial ( P = 0.461 ) . D. sophia taste was less tolerated . Conclusions : D. sophia is introduced as a cheap and available medication which can be applied as a safe alternative to conventional PEG in the management of pediatric chronic functional constipation Objectives : The aim of the study was to evaluate the effectiveness and safety of 2 different polyethylene glycol ( PEG ) doses for the maintenance treatment of functional constipation in children . Methods : Children with functional constipation according to the Rome III criteria were r and omly assigned to receive PEG 4000 at a dose of either 0.7 g/kg ( high-dose group ; n = 45 ) or 0.3 g/kg ( low-dose group ; n = 47 ) for 6 weeks . Adjustment of the therapy was recommended in the event of <3 bowel movements ( BM ) per week or ≥3 BM per day . The primary outcome measure was treatment success , defined as ≥3 BM per week with no fecal soiling during the last week of the intervention . Results : A total of 90 of 92 r and omized children , with a mean age of 3.7 ± 2.1 years , completed the study . In the analysis based on allocated treatment , treatment success was similar in both groups ( relative risk 0.9 , 95 % confidence interval 0.78–1.03 ) . Compared with the high-dose PEG group , the low-dose PEG group had an increased need for therapy adjustment of borderline significance ( relative risk 2.0 , 95 % confidence interval 1.0–4.2 ) , an increased risk of painful defecation , a lower number of stools per week , and lower parental satisfaction . Adverse events were similar in both groups . Conclusions : To achieve treatment success , both tested doses of PEG were equally safe and effective in the treatment of children with functional constipation Background Chronic constipation is frequent in children . The objective of this study is to compare the efficacy and safety of PEG 4000 and lactulose for the treatment of chronic constipation in young children . Methods This r and omised , double-blind study enrolled 88 young children aged 12 to 36 months , who were r and omly assigned to receive lactulose ( 3.3 g per day ) or PEG 4000 ( 8 g per day ) for four weeks . The primary efficacy variable was stool frequency during the fourth week of treatment . Secondary outcomes were the number and frequency of subjective symptoms associated with defecation at each visit . Results Stool frequency was comparable in the two groups at baseline ( lactulose : 0.7 ± 0.5 ; PEG 4000 : 0.5 Output:

Patients who received PEG were significantly less likely to require additional laxative therapies . Common adverse events in these studies included diarrhoea , abdominal pain , nausea , vomiting and pruritis ani . The pooled analyses suggest that PEG preparations may be superior to placebo , lactulose and milk of magnesia for childhood constipation . There is also evidence suggesting the efficacy of liquid paraffin ( mineral oil ) . There is no evidence to demonstrate the superiority of lactulose when compared to the other agents studied , although there is a lack of placebo controlled studies .

MS214159

***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 Difficulties in the palpation of anatomical l and marks in pregnancy due to obesity may create problems in the regional anaesthesia . Objective of this study was to compare ultrasound examination carried out before the procedure with conventional spinal anaesthesia method with papation of bony l and marks in caesarean sections performed under spinal anaesthesia in obese pregnants . Ninety-seven obese pregnants having pre- and post-pregnancy body mass index > 30 kg/m2 were prospect ively examined . Patients were r and omised to two groups as l and mark group ( n = 49 ) and ultrasound group ( n = 48 ) . The needle insertion point was determined at L4–L5 level before the procedure through palpation in the l and mark group and with the examination in the ultrasound . The numbers of skin punctures and needle passes , total procedure time ( TPT ) and spinal block occurrence time ( SBOT ) were recorded . TPT was significantly longer in the ultrasound than in the l and mark group ( p < 0.001 ) ( 8 ± 2 and 5 ± 1 ; respectively ) . Whereas SBOT values were similar ( p = 0.063 ) . The numbers of skin punctures and needle passes were significantly fewer in the ultrasound than in the l and mark group ( p < 0.001 ) . We believe that , accurate determination of the needle introducing site before the procedure by viewing the vertebral structures through ultrasound examination in obese pregnants could increase the success rate Ultrasound assistance for neuraxial techniques may improve technical performance ; however , it is unclear which population s benefit most . Our study aim ed to investigate the efficacy of neuraxial ultrasound in women having caesarean section with combined spinal‐epidural anaesthesia , and to identify factors associated with improved technical performance . Two‐hundred and eighteen women were r and omly allocated to ultrasound‐assisted or control groups . All the women had a pre‐procedure ultrasound , but only women in the ultrasound group had this information conveyed to the anaesthetist . Primary outcomes were first‐pass success ( a single needle insertion with no redirections ) and procedure difficulty . Secondary outcomes were block quality , patient experience and complications . Exploratory sub‐group analysis and regression analysis were used to identify factors associated with success . Data from 215 women were analysed . First‐pass success was achieved in 67 ( 63.8 % ) and 42 ( 38.2 % ) women in the ultrasound and control groups , respectively ( adjusted p = 0.001 ) . Combined spinal‐epidural anaesthesia was ‘ difficult ’ in 19 ( 18.1 % ) and 33 ( 30.0 % ) women in the ultrasound and control groups , respectively ( adjusted p = 0.09 ) . Secondary outcomes did not differ significantly . Anaesthetists misidentified the intervertebral level by two or more spaces in 23 ( 10.7 % ) women . Sub‐group analysis demonstrated a benefit for ultrasound in women with easily palpable spinous processes ( adjusted p = 0.027 ) . Regression analysis identified use of ultrasound and easily palpable spinous processes to be associated with first‐pass success BACKGROUND Ultrasound imaging of the spine is thought to reduce failed and traumatic neuraxial procedures . Most of the evidence supporting this assumption has been produced in the context of an expert sonographer performing the ultrasound assessment , and it remains unknown whether this technique is useful when used by multiple individual operators . OBJECTIVE To invesstigate the impact of preprocedural spinal ultrasound on the ease of insertion of labour epidurals by a group of trainees . We hypothesised that the ultrasound-assisted technique would improve the ease of insertion when compared with the conventional palpation technique . DESIGN A r and omised controlled trial . SETTING Academic hospital in Toronto , Canada . PARTICIPANTS AND INTERVENTION A group of 17 second-year anaesthesia residents and five anaesthesia fellows underwent a training programme in ultrasound assessment of the spine . Parturients with easily palpable lumbar spines were r and omised to either ultrasound or palpation group . Residents and fellows performed both the assessment ( ultrasound or palpation ) and the epidural procedure . MAIN OUTCOME MEASURES Primary outcome : ease of insertion of epidural catheter composed of the time taken to insert the epidural catheter , number of interspace levels attempted and number of needle passes . Secondary outcomes : total procedural time ( assessment and insertion ) ; first pass success rate ; number of attempts required to thread the epidural catheter ; failure of epidural analgesia ; and patient satisfaction . RESULTS We analysed 128 epidural catheter insertions ( residents 84 , fellows 44 ) . There was no difference in median ( interquartile range , IQR ) epidural insertion time between the ultrasound and palpation groups [ 174 ( 120 to 241 ) versus 180 ( 130 to 322.5 ) s , respectively ; P = 0.14 ] . The number of interspace levels attempted and needle passes were also similar in both groups . The total procedural time was longer in the ultrasound group . CONCLUSION The use of preprocedural spinal ultrasound by a cohort of anaesthesia trainees did not improve the ease of insertion of labour epidural catheters in patients with easily palpable lumbar spines , as compared with the traditional palpation technique based on anatomical l and marks . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00996905 STUDY OBJECTIVE To assess the clinical use of ultrasonographic localization of the epidural space , and to evaluate the clinical efficacy of ultrasound diagnostics in obstetric anesthesia . DESIGN R and omized prospect i ve study . SETTING University Clinic of Obstetrics and Gynecology . PATIENTS 300 parturients , 85 of whom had conventional delivery and 65 who underwent cesarean section . INTERVENTIONS Patients underwent ultrasonography for the identification of the intervertebral structures . Puncture depth and angle were measured to improve the placement of the Tuohy needle . MEASUREMENTS In the ultrasound group , additional puncture data , optimized puncture point , expected puncture depth , and angle were used to optimize the puncture technique . To control for side effects , we compiled data on the number of puncture attempts and the number of necessary puncture levels , visual analog scale ( VAS ) scores , the rate of side effects , and the patient acceptance of the technique . MAIN RESULTS The two groups were similar regarding demographic data . Using ultrasound for structure detection , the rate of puncture attempts were significantly ( p < 0.013 ) reduced from 2.18 + /- 1.07 to 1.35 + /- 0.61 . The mean rate of necessary puncture levels was 1.30 + /- 0.55 and with ultrasound detection 1.136 + /- 0.36 ( p < 0.029 ) . Complete analgesia was achieved in 147 patients with ultrasound detection versus 138 patients in the Control group ( p < 0,03 ) . The maximum VAS pain score in the control group was 1.3 + /- 2.1 versus 0.8 + /- 1.5 in the Ultrasound group ( p < 0.006 ) . The rate of side effects were reduced significantly : 99 patients in the Control group had no side effects compared with 120 patients from the Ultrasound group who were free of side effects . Patient acceptance of the technique in the Ultrasound group was significantly higher than in the Control group . CONCLUSION The clinical use of ultrasound for epidural catheter placement may improve regional anesthesia . The use of ultrasound result ed in superior quality in all measured endpoints Palpation method is widely used in clinical practice to identify the puncture site during combined spinal-epidural ( CSE ) blocks . Tuffier ’s line , is an anatomical l and mark between two iliac crests ( inter-cristal ) , which is widely used to identify the puncture site during CSE blocks is not always an indicator for specific vertebral level or inter-vertebral space . One hundred and Ten ( 110 ) women were scheduled for normal vaginal delivery and were r and omized into two equal groups ; palpation group and an ultrasound guided group to detect the efficacy of puncture ultrasound before CSE blocks to increase chances of successful CSE procedure on the first attempt and to reduce the number of attempts or punctures during insertion of CSE catheter . There were no significant differences between two studied groups regarding ; maternal age , weight and height , while , there was a significant difference between two studied groups regarding ; parity . Percentage of successful CSE procedure on the first attempt was significantly higher ( 67.27 % ) in ultrasound compared to palpation group ( 40 % ) . Number of punctures ( attempts ) were significantly less in ultrasound ( 1.2 ± 0.6 ) compared to palpation group ( 2.3 ± 0.8 ) and the number of redirections was also significantly less in ultrasound ( 1.4 ± 0.5 ) compared to palpation group ( 2.8 ± 1.6 ) . Although , time to identify puncture site was significantly longer in ultrasound compared to palpation group and total procedure time was longer in ultrasound ( 9.1 ± 1.5 min ) compared to palpation group ( 6.2 ± 1.2 min ) , there was no significant difference between two studied groups regarding ; time to identify puncture site and total procedure time . Two cases of dural puncture in palpation versus no cases in ultrasound group and two cases of intravascular catheter placement ( one in each group ) , with no significant difference between two groups . Pre- puncture ultrasound guided epidural insertion before vaginal delivery , increases the chance of a successful CSE procedure on the first attempt and reduces the number of attempts during insertion of CSE catheter BACKGROUND Data are scarce on the advantage of ultrasound-guided spinal anaesthesia in patients with easily identifiable bony l and marks . In this study , we compared the use of ultrasound to the l and mark method in patients with no anticipated technical difficulty , presenting for caesarean delivery under spinal anaesthesia . METHODS A total of 150 pregnant women were recruited in this r and omized , controlled study . Ultrasound examination and spinal anaesthesia were performed by three anaesthetists with experience in ultrasound-guided neuraxial block . Patients were r and omized to either the Ultrasound Group ( n=75 ) or the L and mark Group ( n=75 ) . In both groups the level of L3 - 4 or L4 - 5 was identified by ultrasound ( transverse and longitudinal approach ) or palpation . The primary outcome was the procedure time , measured from the time of skin puncture by the introducer to the time of viewing cerebrospinal fluid at the hub of the spinal needle . Secondary outcomes were the number of skin punctures , number of passes , and incidence of successful spinal blockade . RESULTS The average procedure time , number of skin punctures and needle passes , were similar in both groups . The number of patients with successful spinal anaesthesia after one puncture was not statistically different between the groups . CONCLUSION The present results indicate that when performed by anaesthetists experienced in both ultrasound and l and mark techniques , the use of ultrasound does not appear to increase the success rate of spinal anaesthesia , or reduce the procedure time or number of attempts in obstetric patients with easily palpable spines Background and Aims : Identification of subarachnoid space in pregnant patients can pose a great challenge to anaesthesiologists . This study was design ed to compare conventional l and mark technique with pre-procedural ultrasonography-assisted midline approach for identification of the subarachnoid space in elective caesarean section . Methods : After institute ethics committee approval and written informed consent , 100 parturients scheduled for elective caesarean section under spinal anaesthesia were included in this prospect i ve r and omised control trial and divided into Group L ( n = 50 ) ( l and mark technique ) and Group U ( n = 50 ) ( ultrasound-guided technique ) . Parameters such as time taken for the identification of the interspace , distance between skin and dura mater , number of insertion attempts ( the primary outcome ) , number of passes and time taken were recorded in both the groups . Statistical analysis was done using SPSS software 16 . Results : Demographic profiles of both groups were comparable . The number of attempts for needle insertion ( 1.04 ± 0.19 vs. 1.97 ± 0.77 ) , number of passes in the same interspinous space ( 1.26 ± 0.44 vs. 1.90 ± 0.51 ) and the total time for successful lumbar puncture ( 31.90 ± 6.30 vs. 51.80 ± 12.28 s ) were significantly less in Group U as compared to Group L , but the time of identification of interspinous space was significantly more in Group U ( 56.70 ± 13.08 s ) as compared to Group L ( 47.10 ± 10.45 s ) . Conclusion : Pre-procedural ultrasound is a useful tool for successful lumbar puncture in parturients as it reduces the number of attempts with fewer side effects as compared to conventional l and mark technique STUDY OBJECTIVE This r and omized controlled trial was design ed to evaluate the efficacy of additional information from preprocedure ultrasound examination to aid anesthesiology trainees performing spinal anesthesia for obstetric patients . DESIGN Trainee residents were r and omly allocated to Output:

The primary results showed that preprocedural ultrasound increased the FPS rate in patients with predicted puncture difficulty but not in patients who were easily punctured . Preprocedural ultrasound reduced the number of redirections and punctures and decreased the incidence of vascular puncture and backache . There was no evidence of a reduction in failed punctures . We also noted that preprocedural ultrasound prolonged the identification time but not the procedure time . Thus , this systematic review provides evidence that preprocedural ultrasound does not improve the FPS rate of neuraxial anesthesia in patients who are easily palpated , although it increases the FPS rate in patients who are difficult to palpate

MS214160

***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 objective of this study was to compare the relationship between repeated momentary reports of stress and headaches in female adolescents with varying degrees of headache frequency . BACKGROUND Headaches are the most common form of pain reported by adolescents affecting more than a third of all adolescents . High levels of stress during adolescence may predispose an adolescent to experience headaches in adulthood . R and omized , momentary data collection of stress and headaches provides the most accurate data regarding the adolescent experience of these variables . METHODS The research methodology , ecological momentary assessment , is a valid approach to better underst and the relationship between stress and headaches in adolescence . Data were obtained by each participant 's use of an electronic diary ( ED ) , which captured repeated momentary reports of perceived stress , head pain , and stress-related symptoms in female adolescents with varying degrees of recurrent headache . Seven times per day for the 21-day study period , teen girls responded to ED questions about their current stress levels , head pain , and stress-related symptoms . Based on participants ' momentary reports of headaches , Low Headache , Moderate Headache , and Chronic Headache groups were created . General estimating equation models were used to analyze the relationship between momentary variables as well as the lag effect between stress and head pain . RESULTS Thirty-one participants , aged 14 - 18 years , completed 2841 r and omized ED reports and reported 674 occurrences of headache . The Chronic Headache and Moderate Headache groups reported significantly increased levels of stress , head pain , and headaches . The relationship between momentary stress and head pain was significantly strong both within and across participants . The strength of this relationship increased with increased headache activity . A significant lag effect was found between stress and headaches ; however , the effect of depression as a moderator of the stress and headache relationship remains unclear . CONCLUSION Perceived stress and head pain was highly correlated in these female adolescents . Given the large population of teens affected by headaches , a plausible next step would be to vali date these results in other sample s and to determine methods with which to identify teens who may be at risk for a pattern of increasing stress and headaches Background Research examining adolescent mood , stresses , and coping has tended to use retrospective question naires which are affected by recall biases . The aim of this study was to develop , pilot , and evaluate a youth-friendly mobile phone program to monitor , in real-time , young people ’s everyday experiences of mood , stress , and their coping behaviours . Method and design A momentary sampling program was design ed for mobile phones , and ran for 7 days , administering a brief question naire four r and om times each day , capturing information on current activity , mood , responses to negative mood , stresses , alcohol and cannabis use . Eleven high school students review ed the program in focus groups , and 18 students completed 7 days of monitoring . Results Engagement with the mobiletype program was high with 76 % of 504 possible entries completed and 94 % ( 17/18 ) of the participants reporting that the program adequately captured their moods , thoughts , and activities . The mobiletype program captured meaningful and analyzable data on the way young people ’s moods , stresses , coping strategies , and alcohol and cannabis use , vary both between and within individuals . Conclusions The mobiletype program captured a range of detailed and interesting qualitative and quantitative data about young people ’s everyday mood , stresses , responses , and general functioning INTRODUCTION AND AIMS Alcohol use during adolescence is associated with the onset of alcohol use disorders , mental health disorders , substance abuse as well as socially and physically damaging behaviours , the effects of which last well into adulthood . Nevertheless , alcohol use remains prevalent in this population . Underst and ing motivations behind adolescent alcohol consumption may help in developing more appropriate and effective interventions . This study aims to increase this underst and ing by exploring the temporal relationship between mood and different levels of alcohol intake in a sample of young people . DESIGN AND METHODS Forty-one secondary school students used a purpose - design ed mobile phone application to monitor their daily mood and alcohol use for 20 r and om days within a 31 day period . Generalised estimating equations were used to examine the relationship between differing levels of alcohol consumption ( light , intermediate and heavy ) and positive and negative mood three days before and after drinking episodes . RESULTS While there was no relationship between light and heavy drinking and positive mood , there was an increase in positive mood before and after the drinking event for those that drank intermediate amounts . No statistically significant relationships were found between negative mood and any of the three drinking categories . DISCUSSION AND CONCLUSION Adolescents who drank in intermediate amounts on a single drinking occasion experienced an increase in positive mood over the three days leading up to and three days following a drinking event . These findings contribute to an underst and ing of the motivations that underpin adolescent alcohol use , which may help inform future interventions The objective of this study was to identify physical , social , and intrapersonal cues that were associated with the consumption of sweetened beverages and sweet and salty snacks among adolescents from lower SES neighborhoods . Students were recruited from high schools with a minimum level of 25 % free or reduced cost lunches . Using ecological momentary assessment , participants ( N=158 ) were trained to answer brief question naires on h and held PDA devices : ( a ) each time they ate or drank , ( b ) when prompted r and omly , and ( c ) once each evening . Data were collected over 7days for each participant . Participants reported their location ( e.g. , school grounds , home ) , mood , social environment , activities ( e.g. , watching TV , texting ) , cravings , food cues ( e.g. , saw a snack ) , and food choices . Results showed that having unhealthy snacks or sweet drinks among adolescents was associated with being at school , being with friends , feeling lonely or bored , craving a drink or snack , and being exposed to food cues . Surprisingly , sweet drink consumption was associated with exercising . Watching TV was associated with consuming sweet snacks but not with salty snacks or sweet drinks . These findings identify important environmental and intrapersonal cues to poor snacking choices that may be applied to interventions design ed to disrupt these food-related , cue-behavior linked habits Computerized ecological momentary assessment ( EMA ) is widely accepted as a “ gold st and ard ” method for capturing momentary symptoms repeatedly experienced in daily life . Although many studies have addressed the within-individual temporal variations in momentary symptoms compared with simultaneously measured external criteria , their concurrent associations , specifically with continuous physiological measures , have not been rigorously examined . Therefore , in the present study , we first examined the variations in momentary symptoms by validating the associations among self-reported symptoms measured simultaneously ( depressive mood , anxious mood , and fatigue ) and then investigated covariant properties between the symptoms ( especially , depressive mood ) and local statistics of locomotor activity as the external objective criteria obtained continuously . Healthy subjects ( N = 85 ) from three different population s ( adolescents , undergraduates , and office workers ) wore a watch-type computer device equipped with EMA software for recording the momentary symptoms experienced by the subjects . Locomotor activity data were also continuously obtained by using an actigraph built into the device . Multilevel modeling analysis confirmed convergent associations by showing positive correlations among momentary symptoms . The increased intermittency of locomotor activity , characterized by a combination of reduced activity with occasional bursts , appeared concurrently with the worsening of depressive mood . Further , this association remained statistically unchanged across groups regardless of group differences in age , lifestyle , and occupation . These results indicate that the temporal variations in the momentary symptoms are not r and om but reflect the underlying changes in psychophysiological variables in daily life . In addition , our findings on the concurrent changes in depressive mood and locomotor activity may contribute to the continuous estimation of changes in depressive mood and early detection of depressive disorders BACKGROUND Variables that are thought to precipitate migraine or tension-type headache episodes in children hitherto have only been studied using retrospective reports . As such , there is little empirical evidence to support the actual predictive association between presumed headache triggers and actual headache occurrence in children . OBJECTIVE The present study sought to determine if fluctuations in weather , a commonly reported headache trigger in children , predict increased likelihood of headache occurrence when evaluated using rigorous prospect i ve methodology ( " electronic momentary assessment ") . METHODS Twenty-five children ( 21 girls , 4 boys ) between the ages of 8 - 17 years attending a new patient neurology clinic appointment and having a diagnosis of chronic migraine , chronic tension-type , or episodic migraine headache ( with or without aura ) participated in the study . Children completed baseline measures on headache characteristics , presumed headache triggers , and mood and subsequently were trained in the use of electronic diaries to record information on headaches . Children then completed thrice daily diaries on h and held computers for a 2-week time period ( 42 assessment s per child ) while data on weather variables ( temperature , dew point temperature , barometric pressure , humidity , precipitation , and sunlight ) in the child 's geographic location were recorded each time a diary was completed . Data were analyzed using multilevel models . RESULTS Of the weather variables , relative humidity and presence of precipitation were significantly predictive of new headache onset , with nearly a 3-fold increase in probability of headache occurrence during times of precipitation or elevated humidity in the child 's area , b = 0.38 , t(821 ) = 2.10 , P = .04 , and b = 0.02 , t(821 ) = 2.81 , P = .01 , respectively . These associations remained after accounting for fluctuations in mood , and associations were not significantly stronger in children who at baseline thought that weather was a headache trigger for them . Changes in temperature , dew point temperature , barometric pressure , and sunlight were not significantly predictive of new headache episode occurrence in this sample . CONCLUSIONS Results of the present study lend some support to the belief commonly held by children with recurrent headaches that weather changes may contribute to headache onset . Although electronic momentary assessment methodology was found to be feasible in this population and to have the potential to identify specific headache triggers for children , it remains to be determined how best ( or even whether ) to incorporate this information into treatment recommendations This study uses ecological momentary assessment ( EMA ) to simultaneously capture youths ' perceptions of peer affiliates and social context s to determine their association with youths ' current and future mood states . A sample of 82 seventh grade students ( 36 at risk for developing or escalating rule breaking and substance use and 46 r and omly selected ) from 4 schools participated . Using EMA methodology , we had students report their peer affiliations , perceptions of peer affiliates , moods , activities , location , and behaviors during their free time . Data from 3 assessment waves were collected ; each wave consisted of 27 r and omly prompted assessment s during a week . Youths spent a large portion of their free time watching television , on the computer , or playing video games . Being " out and about " increased over the school year , whereas adult supervision decreased , showing an increase in potentially risky situations . Happiness was associated with affiliating with peers who were perceived to be popular . Negative moods were associated with affiliating with peers by whom they were teased or treated meanly . Multilevel models found that both levels and lability of negative moods ( i.e. , sadness , anxiety ) were predicted by risk status and affiliation with peers who tease them . Compared with boys , girls who affiliated more with peers who teased them and were classified as at risk had more extreme negative moods and negative mood lability . EMA methodology has demonstrated the ways in which salient intrapersonal and peer processes are associated over time , which can inform efforts to prevent the development and escalation of behavior problems , substance use , and mood disorders in adolescence Paper diaries are commonly used in health care and clinical research to assess patient experiences . There is concern that patients do not comply with diary protocol s , possibly invalidating the benefit of diary data . Compliance with paper diaries was examined with a paper diary and with an electronic diary that incorporated compliance-enhancing features . Participants were chronic pain patients and they were assigned to use either a paper diary instrumented to track diary use or an electronic diary that time-stamped entries . Participants were instructed to make three pain entries per day at predetermined times for 21 consecutive days . Primary outcome measures were reported vs actual compliance with paper diaries and actual compliance with paper diaries ( defined by comparing the written times and the electronically-recorded times of diary use ) . Actual compliance was recorded by the electronic diary . Participants su bmi tted diary cards corresponding to 90 % of assigned times ( + /-15 min ) . However , electronic records indicated that actual compliance was only 11 % , indicating a high level of faked compliance . On 32 % of all study days the paper diary binder was not opened , yet reported compliance for these days exceeded 90 % . For the electronic diary , the actual compliance rate was 94 % . In summary , participants with chronic pain enrolled in a study for research were not compliant with paper diaries but were compliant with an electronic diary with enhanced compliance features . The findings call into question the use of paper diaries and suggest that electronic diaries with compliance-enhancing features are a more effective way of collecting diary information BACKGROUND Smartphone applications can potentially provide recovery monitoring and support in real-time , real-life context s. Study aims included determining feasibility of ( a ) adolescents completing ecological momentary assessment s ( EMAs ) and utilizing phone-based ecological momentary interventions ( EMIs ) ; and ( b ) using EMA and EMI data to predict substance use in the subsequent week . METHODS Twenty-nine adolescents were recruited at discharge from residential treatment , regardless of their discharge status or length of stay . During the 6-week pilot , youth were prompted to complete an EMA at 6 Output:

The reported compliance rates did not differ by duration of EMA period among studies from either clinical or non clinical setting s. CONCLUSIONS The compliance rate among mobile-EMA studies in youth is moderate but suboptimal . Study design may affect protocol compliance differently between clinical and non clinical participants ; including additional wearable devices did not affect participant compliance .

MS214161

***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 Culture and susceptibility testing of Helicobacter pylori strains was performed in a large multinational , multicenter r and omized clinical trial . Culture was carried out on gastric biopsy sample s obtained from 516 patients at entry and had a sensitivity of 99 % when the [13C]urea breath test was used as a reference . Susceptibility testing was performed for clarithromycin and metronidazole on 485 strains by an agar dilution method and the epsilometer test ( Etest ) and for amoxicillin by an agar dilution method only . Resistance to clarithromycin ( > 1 μg/ml ) was found in 3 % of the H. pylori strains , with a perfect correlation between Etest and agar dilution methods . Resistance to metronidazole ( > 8 μl/ml ) was found in 27 % of the strains by agar dilution , but there were important discrepancies between it and the Etest method . No resistance to amoxicillin was found . The logarithms of the MICs of the three antibiotics against susceptible strains had a distribution close to normal . The impact of resistance was tested in the four arms of the trial . There were not enough clarithromycin-resistant strains to evaluate the impact of resistance on the cure rate of clarithromycin-based regimens . For metronidazole-resistant strains , the impact noted in the clarithromycin-metronidazole arm was partially overcome when omeprazole was added ( 76 % eradication for resistant strains versus 95 % for susceptible strains ) . Secondary resistance to clarithromycin occurred in strains from 12 of 105 patients ( 11.4 % ) after the failure of a clarithromycin-based regimen to effect eradication . The detection of point mutations in clarithromycin-resistant strains was performed by a combination of PCR and restriction fragment length polymorphism . Mutations ( A2142 G and 2143 G ) were found in all strains tested except one . This study stresses the importance of performing susceptibility tests in clinical trials in order to explain the results of different treatments BACKGROUND Helicobacter pylori eradication with omeprazole , amoxycillin , and metronidazole is both effective and inexpensive . However , eradication rates with different dosages and dosing vary , and data on the impact of resistance are sparse . In this study , three different dosages of omeprazole , amoxycillin , and metronidazole were compared , and the influence of metronidazole resistance on eradication was assessed . METHODS Patients ( n = 394 ) with a positive H. pylori screening test result and endoscopy-proven duodenal ulcer in the past were enrolled into a multicenter study performed in four European countries and Canada . After baseline endoscopy , patients were r and omly assigned to treatment for 1 week with either omeprazole , 20 mg twice daily , plus amoxycillin , 1,000 mg twice daily , plus metronidazole , 400 mg twice daily ( low M ) ; or omeprazole , 40 mg once daily , plus amoxycillin , 500 mg three times daily , plus metronidazole , 400 mg three times daily ( medium M ) ; or omeprazole , 20 mg twice daily , plus amoxycillin , 1,000 mg twice daily , plus metronidazole , 800 mg twice daily ( high M ) . H. pylori status at entry was assessed by a 13C urea breath test and a culture . Eradication was defined as two negative 13C-urea breath test results 4 and 8 weeks after therapy . Susceptibility testing using the agar dilution method was performed at entry and in patients with persistent infection after therapy . RESULTS The eradication rates , in terms of intention to treat ( ITT ) ( population n = 379 ) ( and 95 % confidence interval [ CI ] ) were as follows : low M 76 % ( 68 % , 84 % ) , medium M 76 % ( 68 % , 84 % ) , and high M 83 % ( 75 % , 89 % ) . By per- protocol analysis ( population n = 348 ) , the corresponding eradication rates were : low M 81 % , medium M 80 % , and high M 85 % . No H. pylori strains were found to be resistant to amoxycillin . Pre study resistance of H. pylori strains to metronidazole was found in 72 of 348 ( 21 % ) of the cultures at entry ( range , 10%-39 % in the five countries ) . The overall eradication rate in pre study metronidazole-susceptible strains was 232 of 266 ( 87 % ) and , for resistant strains , it was 41 of 70 ( 57 % ; p < .001 ) . Within each group , the results were as follows ( susceptible/resistant ) : low M , 85%/54 % ; medium M , 86%/50 % ; and high M , 90%/75 % . There were no statistically significant differences among the treatment groups . 23 strains susceptible to metronidazole before treatment were recultured after therapy failed ; 20 of these had now developed resistance . CONCLUSIONS H. pylori eradication rates were similar ( approximately 80 % ) with all three regimens . Metronidazole resistance reduced efficacy ; increasing the dose of metronidazole appeared not to overcome the problem or significantly improve the outcome . Treatment failure was generally associated with either pre study or acquired metronidazole resistance . These findings are of importance when attempting H. pylori eradication in communities with high levels of metronidazole resistance Objectives : Rabeprazole is a new fast acting proton pump inhibitor that has recently been proven to be effective in the treatment of peptic ulceration and reflux esophagitis . The aim of this study was to evaluate rabeprazole in combination with antibiotics for the eradication of Helicobacter pylori ( H. pylori ) in patients with chronic active gastritis with or without peptic ulcer disease . Methods : Seventy-five H. pylori-infected patients were r and omized in a double-blind fashion to receive a 7-day treatment regimen consisting of : RAC , RAM , RCM , or RC ( R = rabeprazole 20 mg b.d . , A = amoxycillin 1 g b.d . , C = clarithromycin 500 mg b.d . , M = metronidazole 400 mg b.d . ) . R and omized patients were H. pylori-positive by gastric biopsy urease test , histology and 13C urea breath test ( 13C-UBT ) . H. pylori eradication was assessed by 13C-UBT , 4 and 8 wk after finishing treatment . Endoscopy with histology and culture for antibiotic sensitivity testing was performed pretreatment and if treatment failed . Results : On an intention-to-treat analysis , treatment success was : RCM 100 % , RAC 95 % , RAM 90 % , and RC 63 % . The most common side effects were loose stools , headache , and taste disturbance , but there were no serious adverse events related to the study medication . The two patients failing RAM treatment had metronidazole-resistant strains before and after treatment . None of the pretreatment H. pylori isolates from six patients failing RC were clarithromycin resistant , but three of five successfully cultured posttreatment had developed clarithromycin resistance . Conclusion : Rabeprazole-based triple therapy with two antibiotics for 1 wk is safe and effective in eradicating H. pylori . Dual therapy with clarithromycin is less successful , and the majority of treatment failures develop clarithromycin resistance OBJECTIVES To treat previously untreated adult patients infected with Helicobacter pylori with one of two regimens in an ambulatory community setting to assess the efficacy and safety of these regimens . METHODS Sixty five adult patients with histologically confirmed H. pylori infection were r and omly assigned in this open cohort study to 2 wk , low dose , twice daily treatment with omeprazole 20 mg and clarithromycin 250 mg ( OC ) ( n = 31 ) or OC plus metronidazole 500 mg ( OCM ) ( n = 34 ) . At least 4 wk after treatment , H. pylori status was assessed by histology ( four gastric biopsies , two each from antrum and body ) . RESULTS Triple therapy with OCM was significantly better than dual therapy with OC in intent-to-treat ( 82.4 vs 58.1 % , p = 0.03 ) and per protocol analysis ( 93.3 vs 62.1 % , p = 0.004 ) . Although there were frequent side effects ( OC 19/31 61.3 % ; OCM 22/34 64.7 % with at least one side effect ) , these were generally mild , and patients were able to complete nearly all of their medications ( OC 97.2 % , OCM 96.7 % of pills taken ) . The only patient withdrawn due to medication side effects was in the OC arm . CONCLUSIONS Triple therapy with OCM in a community setting eradicates H. pylori more effectively than dual therapy with OC . OCM is tolerated with high compliance despite frequent minor side effects and appears safe without the development of serious adverse events OBJECTIVES Triple therapy and amoxycillin plus omeprazole are the two most widely recommended regimens for the eradication of Helicobacter pylori . However , no controlled studies with a large number of cases are available for the reliable comparison of these two regimens . The aim of this controlled , r and omized , prospect i ve study was to compare the effect of these two regimens and a further regimen for metronidazole-resistant patients on duodenal ulcer healing , H. pylori eradication , and prevention of ulcer relapse . METHODS Patients ( n = 144 ) with proven duodenal ulcer ( DU ) were r and omized to one of the three following regimens : group A , omeprazole ( 2 x 40 mg ) plus amoxycillin ( 4 x 500 mg ) for 2 wk ; group B , triple therapy : bismuth nitrate ( 4 x 375 mg ) plus metronidazole ( 4 x 250 mg ) and tetracycline ( 4 x 500 mg ) daily for 2 wk and ranitidine ( 150 mg ) for the first week and bismuth nitrate ( 4 x 375 mg ) alone for a further 2 wk ; group C , omeprazole ( 20 mg ) plus amoxycillin ( 4 x 500 mg ) and tinidazole ( 2 x 500 mg ) for 2 wk . RESULTS A total of 46 patients in group A , 39 in group B , and 43 in group C completed the study . One patient in group A and three in group B did not tolerate the regimens and dropped out of the study . Control endoscopy was performed 8 wk after the start of treatment and when symptoms appeared ( up to 1 yr after the start of treatment ) . In subjects who completed the study , both the healing rate of DU in group B ( 97 % compared with 74 and 73 % in A and C , respectively , p < 0.02 ) and the H. pylori eradication rate in group B ( 85 compared with 35 % , p < 0.0001 in A and 58 % , p < 0.02 , in C ) were significantly higher than in groups A and C. The symptomatic ulcer relapse during the 1-yr follow-up in patients with initially healed ulcers was similar in all groups ( 18 , 16 , and 19 % in A , B , and C , respectively ) . The predictor of healing using logistic regression analysis was night pain ( p < 0.05 ) . The predictor of H. pylori eradication was sex ( p < 0.05 ) . CONCLUSION The 2-wk triple therapy plus an additional 2-wk treatment with the bismuth derivative ( without a prolonged administration of acid suppressing drugs ) seems to be an effective and economic treatment not only for the eradication of H. pylori but also for the healing of acute DU . The higher incidence of side effects found after triple therapy compared with the other two regimens was tolerated by the patients : In Asian countries with limited re sources , clarithromycin‐based triple therapy may not be readily available . There are also few direct comparisons of different regimens in Asia OBJECTIVES Our objectives were to determine the effect of dual therapy with omeprazole and amoxicillin and of triple therapy with omeprazole , amoxicillin , and metronidazole in the eradication of Helicobacter pylori ( HP ) and to study the long-term results of eradication in these patients . METHODS A prospect i ve , r and omized , controlled trial was performed . Patients who were recruited had unequivocal evidence of HP infection based on culture , histology , rapid urease test , and Gram 's stain of a tissue smear . Eradication was defined as the absence of bacteria in all tests performed on both corpus and antral biopsies . RESULTS The infection was eradicated in 15 of 19 ( 78.9 % ) patients r and omized to receive dual therapy and in Output:

RESULTS The data supported the current worldwide recommendation to use proton pump inhibitor (PPI)-based triple therapy with clarithromycin and either metronidazole or amoxycillin . There are , however , regional differences in success rates that are not completely explained by resistance to either metronidazole or amoxycillin . For second-line therapy , quadruple therapy using a PPI with bismuth , metronidazole and tetracycline ( PPI-BMT ) is superior to an alternative PPI-based triple therapy .

MS214162

***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 investigate the efficacy of patellar taping on pain control , patellar alignment , and neuromuscular control ( ie , vastus medialis oblique activation , knee extensor moment , etc ) in subjects with patellofemoral pain syndrome . DATA SOURCES We search ed MEDLINE , SPORT Discus , PEDro , and CINAHL through December 2004 , using the key words patellar taping , therapeutic taping , McConnell taping , taping , chronic injury , patellofemoral pain , and knee . STUDY SELECTION Criteria for inclusion criteria were studies that exclusively recruited patients diagnosed with patellofemoral pain syndrome or anterior knee pain and outcome measures specific to pain reduction , neuromuscular control , and patellar positioning . DATA EXTRACTION We identified and review ed 16 studies with an average PEDro score of 4.25/10 . Articles were divided into 3 categories based on primary outcome measures : 4 r and omized controlled trials on treatment methods and pain , 9 studies on neuromuscular control , and 3 on patellar positioning . DATA SYNTHESIS Although patellar taping seems to reduce pain and improve function in people with patellofemoral pain syndrome during activities of daily living and rehabilitation exercise , strong evidence to identify the underlying mechanisms is still not available BACKGROUND AND PURPOSE Quadriceps strengthening , quadriceps stretching and patellar taping are commonly prescribed together for patellofemoral pain patients . This study aim ed to examine the effectiveness of each of these techniques in isolation for one week and in combination for one week . METHODS A prospect i ve double-blind r and omized control study was design ed involving 41 subjects with 60 knees diagnosed with patellofemoral pain . The knees were r and omized in onto one of four groups ( n = 15 ) : infrapatellar taping , quadriceps strengthening , quadriceps stretching and control . The taping was worn continually for the week ; the strengthening group followed a programme of non-weight-bearing terminal range quadriceps exercises , the stretching group performed rectus femoris stretches . The control group did not receive treatment . All subjects received advice . Seven pre- and post-treatment measures included isokinetic quadriceps strength , quadriceps length , pain measured during four activities and maximum eccentric , posturally controlled , pain-free knee flexion angle during a step-down . Results showed significant changes over time ( p < 0.01 ) in two out of seven measures for the taping group , in five out of seven for the strengthening group and five out of seven for the stretching group and none in the control group . When the three modalities were combined for one week , ( n = 60 ) all seven measures improved significantly ( p < 0.01 ) . CONCLUSION In isolation , quadriceps stretching and quadriceps strengthening result ed in more improvements than taping . Combining these treatments is recommended as the initial approach to treating patellofemoral pain but further individualized more functional , global treatment is essential Abstract Although patellar taping has been shown to reduce pain in participants with patellofemoral pain syndrome , the mechanisms of pain reduction have not completely been established following its application . The purpose of this study was to evaluate EMG activity of vastus medialis and vastus lateralis following the application of patellar taping during a functional single leg squat . Both vastus medialis obliquus – vastus lateralis onset and vastus medialis obliquus/vastus lateralis amplitude of 18 participants with patellofemoral pain syndrome and 18 healthy participants as controls were measured using an EMG unit . This procedure was performed on the affected knee of participants with patellofemoral pain syndrome , before , during , and after patellar taping during unilateral squatting . The same procedure was also performed on the unaffected knees of both groups . The mean values of vastus medialis obliquus – vastus lateralis onset prior to taping ( 2.54 ms , s = 4.35 ) were decreased significantly following an immediate application of tape ( −3.22 ms , s = 3.45 ) and after a prolonged period of taping ( −6.00 ms , s = 3.40 s ) ( P < 0.05 ) . There was also a significant difference between the mean values of vastus medialis obliquus – vastus lateralis onset among controls ( −2.03 ms , s = 6.04 ) and participants with patellofemoral pain syndrome prior to taping ( P < 0.05 ) . However , there were no significant difference between the ranked values of vastus medialis obliquus/vastus lateralis amplitude of the affected and unaffected knees of participants with patellofemoral pain syndrome and controls during different conditions of taping ( P > 0.05 ) . Decreased values of vastus medialis obliquus – vastus lateralis onset may contribute to patellar realignment and explain the mechanism of pain reduction following patellar taping in participants with patellofemoral pain syndrome Background Since knee complaints are common among athletes and are frequently presented in general practice , it is of interest to investigate the type of knee complaints represented in general practice of athletes in comparison with those of non-athletes . Therefore , the aim of this study is to investigate the differences in type of knee complaints between sport participants , in this study defined as athletes , and non-sport participants , defined as non-athletes , presenting in general practice . Further , differences in the initial policy of the GP , medical consumption , and outcome at one-year follow-up were also investigated . Methods Patients consulting their GP for a new episode of knee complaints were invited to participate in this prospect i ve cohort study . From the total HONEUR knee cohort population ( n = 1068 ) we extracted patients who were athletes ( n = 421 ) or non-athletes ( n = 388 ) . Results The results showed that acute distortions of the knee were significantly more diagnosed in athletes than in non-athletes ( p = 0.04 ) . Further , more athletes were advised by their GP to ' go easy on the knee ' than the non-athletes ( p < 0.01 ) , but no differences were found in number of referrals and medication prescribed by the GP . The medical consumption was significantly higher among athletes ; however , no significant differences were found between the two groups for recovery at one-year follow-up . Conclusion There are no major differences in the diagnosis and prognosis of knee complaints between athletes and non-athletes presented to the GP . This implies that there are no indications for different treatment strategies applied in both groups . However , athletes are more often advised to ' go easy on the knee ' and to rest than non-athletes . Further , there is a trend towards increased medical consumption among athletes while functional disability and pain are lower than among the non-athletes OBJECTIVE The purpose of this prospect i ve , r and omized , controlled study was to determine the effects of kinesio taping in the treatment of patients with patellofemoral pain syndrome ( PFPS ) . METHODS Thirty-one women with PFPS ( mean age : 44.88 years ; range : 17 to 50 years ) were r and omly assigned to either a kinesio taping ( KT ) ( n=15 ) or control ( n=16 ) group . Both groups received the same muscle strengthening and soft tissue stretching exercises for six weeks and the KT group additionally received kinesio taping at four day intervals for six weeks . Visual analog scale was used to measure pain intensity . Tension of the iliotibial b and /tensor fascia lata and hamstring muscles and the mediolateral location of the patella were measured before the treatment and at the end of the third and sixth week . The Anterior Knee Pain Scale / Kujala Scale was used for the analysis of functional performance . RESULTS Comparing pretreatment and 6th week values , significant improvements were found in pain , soft tissue flexibility and functional performance of both groups ( p<0.05 ) . However , patellar shift was unchanged ( p>0.05 ) . The KT group had significantly better hamstring flexibility than the control group at the end of three weeks ( p<0.05 ) . CONCLUSION The addition of kinesio taping to the conventional exercise program does not improve the results in patients with PFPS , other than a faster improvement in hamstring muscle flexibility The aim of this study was to assess the effect of patellar taping of the proprioceptive status of patients with patellofemoral pain syndrome ( PFPS ) . A total of 32 subjects ( 18 males , 14 females of age 31.9 + /- 11.2 , body mass index 25.8 + /- 5.3 ) with PFPS were tested for Joint Position Sense ( JPS ) using a Biodex dynamometer . Outcomes of interest were the absolute error ( AE ) , the variable error ( VE ) and the relative error ( RE ) of the JPS values for both active ( AAR ) and passive ( PAR ) angle reproduction at an angular velocity of 2 degrees /s with a start angle at 90 degrees and target angles of 60 degrees and 20 degrees . Taping was applied in r and om order across the patella of each subject with each of the subjects acting as their own internal control . Results indicated initially that application of patellar tape did not enhance and in some cases worsened the JPS of the subjects ( P > 0.05 ) . However , when the subjects ' proprioceptive status was grade d according to their closeness to the target angles into ' good ' ( 5 degrees , N = 10 ) and ' poor ' ( > 5 degrees , N = 22 ) taping enhanced nearly all values of those with ' poor ' proprioception , with AE at 20 degrees to statistical significance ( P = 0.021 ) . In conclusion , this study has shown that patellar taping did not improve the AAR and PAR JPS tests of a whole sample of 32 PFPS patients . It also has shown that a subgroup of PFPS patients with poor proprioception may exist and be helped by patellar taping STUDY DESIGN A r and omized controlled trial . OBJECTIVES To investigate the effectiveness of daily patella taping and exercise on pain and function in individuals with patellofemoral pain syndrome . BACKGROUND Patella taping and muscle-strengthening programs are commonly used to treat patellofemoral pain syndrome . There is , however , little evidence for the effectiveness of these approaches . METHODS AND MEASURES Twenty-four men and 6 women aged 17 to 25 years ( mean + /- SD , 18.7 + /- 1.2 years ) participated in the study . Subjects were r and omly and exclusively assigned to 1 of 3 treatment groups : patella taping combined with a st and ardized exercise program , placebo patella taping and exercise program , or exercise program alone ( n = 10 in each group ) . Taping was applied and exercises performed on a daily basis for 4 weeks . Outcome measures were visual analog scales for pain and the functional index question naire , recorded at weekly intervals by a therapist who was blinded to group allocation . RESULTS Separate mixed-model ANOVAs , with repeated measures on time , indicated statistically significant improvements in pain and function over time for all groups ( P<.01 ) and also significant differences between groups for all measures ( P<.01 ) . Separate independent sample s t tests showed that the group receiving taping and exercises had better pain and function scores following treatment than the placebo taping- and -exercise group and the exercise-alone group . There were no significant differences between the placebo taping- and -exercise group and exercise-alone group at any time point . CONCLUSIONS These findings indicate that over a period of 4 weeks a combination of daily patella taping and exercises was successful in improving pain and function in individuals with patellofemoral pain syndrome . The combination of patella taping and exercise was superior to the use of exercise alone Objective : To examine the immediate effects of experimentally induced anterior knee pain ( AKP ) on involuntary and voluntary quadriceps strength and activation . Design : Crossover 3 × 3 r and omized controlled laboratory study with repeated measures . Setting : Human Performance Research Center , Brigham Young University . Participants : Thirteen neurologically sound volunteers ( age , 21.9 ± 3.2 years ) . Interventions : Subjects underwent 3 different conditions ( pain , sham , and control ) . To induce AKP and sham condition , 5 % sodium chloride and 0.9 % sodium chloride ( total volume of 1.0 mL for each condition ) , respectively , were injected into the infrapatellar fat pad on the dominant leg . No injection was performed for the control condition . Main Outcome Measures : The vastus medialis peak Hoffmann reflex normalized by the peak motor response ( H : M ratio ) was used to measure involuntary quadriceps activation . Quadriceps central activation ratio ( CAR ) using maximal isometric knee extension torque ( N·m ) was calculated to assess voluntary quadriceps activation . The visual analog scale was used to measure pain perception . Results : Our pain model increased perceived pain immediately after the 5 % hypertonic saline injection and pain lasted for 12 minutes on average ( F40,743 = 16.85 , P < 0.001 ) . During the pain condition , subjects showed a 12 % decrease in H : M ratio ( F2,59 = 8.64 , P < 0.001 ) , a 34 % decrease in maximal isometric knee extension torque ( F2,59 = 5.89 , P < 0.01 ) , and a 5 % decrease in CAR ( F2,59 = 3.83 , P = 0.03 ) . Conclusions : Our data showed that joint pain may be an independent factor to alter function of the muscles surrounding the painful joint . Both involuntary and voluntary inhibitory pathways may play a role in an immediate reduction of muscle activation STUDY DESIGN A multicenter , single-masked study of patients with patellofemoral pain syndrome ( PFPS ) using a repeated- measures design . OBJECTIVE To compare 3 different methods of patellar taping for Output:

There is moderate evidence that ( 1 ) tailored ( customised to the patient to control lateral tilt , glide and spin ) and untailored patellar taping provides immediate pain reduction of large and small effect , respectively and ( 2 ) tailored patellar taping promotes earlier onset of vastus medialis oblique ( VMO ) contraction ( relative to vastus lateralis contraction ) . There is limited evidence that ( 1 ) tailored patellar taping combined with exercise provides superior pain reduction compared to exercise alone at 4 weeks , ( 2 ) untailored patellar taping added to exercise at 3 - 12 months has no benefit and ( 3 ) tailored patellar taping promotes increased internal knee extension moments . CONCLUSIONS Tailoring patellar taping application ( ie , to control lateral tilt , glide and spin ) to optimise pain reduction is important for efficacy . Possible mechanisms behind patellar taping efficacy include earlier VMO onset and improved knee function capacity ( ie , ability to tolerate greater internal knee extension moments )

MS214163

***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 compare the effect of individual educational visits versus group visits using academic detailing to discuss prescribing of highly anticholinergic antidepressants in elderly people . Design : R and omised controlled trial with three arms ( individual visits , group visits , and a control arm ) . Setting : Southwest Netherl and s. Participants : 190 general practitioners and 37 pharmacists organised in 21 peer review groups were studied using a data base covering all prescriptions to people covered by national health insurance in the area ( about 240 000 ) . Intervention : All general practitioners and pharmacists in both intervention arms were offered two educational visits . For physicians in groups r and omised to the individual visit arm , 43 of 70 general practitioners participated ; in the group visit intervention arm , five of seven groups ( 41 of 52 general practitioners ) participated . Main outcome measures : Numbers of elderly people ( 60 years ) with new prescriptions of highly anticholinergic antidepressants and less anticholinergic antidepressants . Results : An intention to treat analysis found a 26 % reduction in the rate of starting highly anticholinergic antidepressants in elderly people ( 95 % confidence interval —4 % to 48 % ) in the individual intervention arm and 45 % ( 8 % to 67 % ) in the group intervention arm . The use of less anticholinergic antidepressants increased by 40 % ( 6 % to 83 % ) in the individual intervention arm and 29 % ( —7 % to 79 % ) in the group intervention arm . Conclusions : Both the individual and the group visits decreased the use of highly anticholinergic antidepressants and increased the use of less anticholinergic antidepressant in elderly people . These approaches are practical means to improve prescribing by continuing medical education Background —This trial tested the effects of multidisciplinary group clinic appointments on the primary outcome of time to first heart failure ( HF ) rehospitalization or death . Methods and Results —HF patients ( n=198 ) were r and omly assigned to st and ard care or st and ard care plus multidisciplinary group clinics . The group intervention consisted of 4 weekly clinic appointments and 1 booster clinic at month 6 , where multidisciplinary professionals engaged patients in HF self-management skills . Data were collected prospect ively for 12 months beginning after completion of the first 4 group clinic appointments ( 2 months post r and omization ) . The intervention was associated with greater adherence to recommended vasodilators ( P=0.04 ) . The primary outcome ( first HF-related hospitalization or death ) was experienced by 22 ( 24 % ) in the intervention group and 30 ( 28 % ) in st and ard care . The total HF-related hospitalizations , including repeat hospitalizations after the first time , were 28 in the intervention group and 45 among those receiving st and ard care . The effects of treatment on rehospitalization varied significantly over time . From 2 to 7 months post r and omization , there was a significantly longer hospitalization-free time in the intervention group ( Cox proportional hazard ratio=0.45 ( 95 % confidence interval , 0.21–0.98 ; P=0.04 ) . No significant difference between groups was found from month 8 to 12 ( hazard ratio=1.7 ; 95 % confidence interval , 0.7–4.1 ) . Conclusions —Multidisciplinary group clinic appointments were associated with greater adherence to selected HF medications and longer hospitalization-free survival during the time that the intervention was underway . Larger studies will be needed to confirm the benefits seen in this trial and identify methods to sustain these benefits . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT00439842 Background : Over the past decade , group medical visits have become more prevalent . Group medical visits may have some advantages in treating chronic illnesses such as chronic pain as they can be more patient centered . The empowerment model is a novel approach used to provide support , education , and healthy activities guided by participants . Objective : To evaluate the early stages of a chronic pain group medical visit program based on the empowerment model . Methods : This prospect i ve cohort study recruited 60 female participants to participate between October 2004 and May 2005 . All enrolled participants completed the SF-36 question naire , which was administered at baseline and again after 6 months of participation . Data from chart review included age , race , weight , height , chronic illness , chronic pain diagnosis , and degree of participation . Chronic pain diagnoses included back pain , osteoarthritis , fibromyalgia , rheumatoid/inflammatory arthritis , and other/unknown . Results : Forty-two participants were enrolled in the program for 6 months . Their average Charleson Comorbidity Index score was 3.1 ( SD=1.5 ) . Statistically significant changes ( P<.05 ) were seen in the following SF-36 categories : Role-Physical , Bodily Pain , General Health , Social Function , and Mental Health . All factors trended toward improvement , with the largest improvements seen in Role-Physical and Role-Emotional . Conclusion : Participants in the chronic pain group medical visit program had a high degree of comorbidity and poor health related quality of life in regards to functioning . There was improvement in many domains of health-related quality of life Purpose Group medical consultations ( GMCs ) provide individual medical visits conducted within a group of four to eight peer patients . This study evaluated the feasibility and efficacy of GMCs in the follow-up of breast cancer . Methods In this r and omized controlled trial , 38 patients participated in a single GMC ( intervention group ) , while the control group ( n = 31 ) received individual outpatient visits . Feasibility is measured in terms of acceptability , dem and , practicability and costs , integration and implementation , and efficacy . Between-group differences on the efficacy outcomes distress ( SCL-90 ) and empowerment ( CEQ ) , 1 week and 3 months after the visit , were analyzed using ANCOVAs . Results GMCs scored high on most areas of feasibility . Patients in GMCs and individual visits were equally satisfied . Patients and professionals reported more discussed themes in GMCs , despite no between-group differences on information needs prior to the visit . Sixty-nine percent of GMC patients experienced peer support . Costs for GMCs were higher compared to individual visits . However , involving a clinical nurse specialist ( CNS ) instead of a medical specialist reduced costs to the level of individual CNS care . Efficacy outcomes ( distress and empowerment ) were equal in both groups . Conclusion GMCs in this study were feasible . Further optimization of GMCs in future (cost-)effectiveness trials is possible by increasing the frequency of GMCs , stating criteria for the type of professionals , number of patients involved , and time limits . Implication s for Cancer SurvivorsBCS may benefit from GMCs by receiving more information and additional peer support . GMCs cover all aspects of follow-up and may be a good alternative for individual follow-up Background : Group patient visits are medical appointments shared among patients with a common medical condition . This care delivery method has demonstrated benefits for individuals with chronic conditions but has not been evaluated for Parkinson disease ( PD ) . Methods : We conducted a 12-month , r and omized trial of group patient visits vs usual ( one-on-one ) care for patients with PD . Visits were led by one of 3 study physicians , included patients and caregivers , and lasted approximately 90 minutes . Those receiving group visits had 4 sessions over 12 months . The primary outcome measure was feasibility as measured by the ability to recruit participants and by the proportion of participants who completed the study . The primary efficacy outcome was quality of life as measured by the PD Question naire-39 . Results : Thirty patients and 27 caregivers enrolled in the study . Thirteen of the 15 patients r and omized to group patient visits and 14 of the 15 r and omized to usual care completed the study . Quality of life measured 12 months after baseline between the 2 groups was not different ( 25.9 points for group patient visits vs 26.0 points for usual care ; p = 0.99 ) . Conclusions : Group patient visits may be a feasible means of providing care to individuals with PD and may offer an alternative or complementary method of care delivery for some patients and physicians . Classification of evidence : This study provides Class II evidence that group patient visits did not improve quality of life for individuals with PD over a 1-year period CONTEXT Emergency department utilization by chronically ill older adults may be an important sentinel event signifying a breakdown in care coordination . A primary care group visit ( i.e. , several patients meeting together with the provider at the same time ) may reduce fragmentation of care and subsequent emergency department utilization . OBJECTIVE To determine whether primary care group visits reduce emergency department utilization in chronically ill older adults . DESIGN R and omized trial conducted over a 2-year period . SETTING Group-model HMO in Denver , Colorado . PATIENTS 295 older adults ( > or = 60 years of age ) with frequent utilization of outpatient services and one or more chronic illnesses . INTERVENTION Monthly group visits ( generally 8 to 12 patients ) with a primary care physician , nurse , and pharmacist held in 19 physician practice s. Visits emphasized self-management of chronic illness , peer support , and regular contact with the primary care team . MEASURES Emergency department visits , hospitalizations , and primary care visits . RESULTS On average , patients in the intervention group attended 10.6 group visits during the 2-year study period . These patients averaged fewer emergency department visits ( 0.65 vs. 1.08 visits ; P = 0.005 ) and were less likely to have any emergency department visits ( 34.9 % vs. 52.4 % ; P = 0.003 ) than controls . These differences remained statistically significant after controlling for demographic factors , comorbid conditions , functional status , and prior utilization . Adjusted mean difference in visits was -0.42 visits ( 95 % CI , -0.13 to -0.72 ) , and adjusted RR for any emergency department visit was 0.64 ( CI , 0.44 to 0.86 ) . CONCLUSION Monthly group visits reduce emergency department utilization for chronically ill older adults Background : Primary care providers ( PCPs ) in safety net setting s face barriers to optimizing care for patients with diabetes . We conducted this study to assess PCPs ' perspectives on the effectiveness of two language -concordant diabetes self-management support programs . Methods : One year postintervention , we surveyed PCPs whose patients with diabetes participated in a three-arm multiclinic r and omized controlled trial comparing usual care ( UC ) , weekly automated telephone self-management ( ATSM ) support with nurse care management , and monthly group medical visits ( GMVs ) . We compared PCP perspectives on patient activation to create and achieve goals , quality of care , and barriers to care using regression models accounting for within-PCP clustering . Results : Of 113 eligible PCPs caring for 330 enrolled patients , 87 PCPs ( 77 % ) responded to surveys about 245 ( 74 % ) enrolled patients . Intervention patients were more likely to be perceived by PCPs as activated to create and achieve goals for chronic care when compared with UC patients ( st and ardized effect size , ATSM vs UC , + 0.41 , p = 0.01 ; GMV vs UC , + 0.31 , p = 0.05 ) . Primary care providers rated quality of care as higher for patients exposed to ATSM compared to UC ( odds ratio 3.6 , p < 0.01 ) . Compared with GMV patients , ATSM patients were more likely to be perceived by PCPs as overcoming barriers related to limited English proficiency ( 82 % ATSM vs 44 % GMV , p = 0.01 ) and managing medications ( 80 % ATSM vs 53 % GMV , p = 0.01 ) . Conclusions : Primary care providers perceived that patients receiving ATSM support had overcome barriers , participated more actively , and received higher quality diabetes care . These views of clinician stakeholders lend additional evidence for the potential to upscale ATSM more broadly to support PCPs in their care of diverse , multi-linguistic population Objective : To assess whether shared medical appointments ( SMAs ) for neuromuscular patients represent a way of using clinicians ' time efficiently without compromising quality of care for patients . Methods : Patients with a chronic neuromuscular disease ( NMD ) ( n = 272 ) were r and omly allocated to either an SMA or a regular individual annual appointment and followed up for a period of 6 months . Data on re source utilization and quality of life ( EQ-5D ) were collected prospect ively , using a health care perspective . Incremental costs and changes in quality -adjusted life-years ( QALYs ) were computed using a probabilistic decision model . Factors critical to the incremental cost-effectiveness of SMAs were explored in sensitivity analyses . Results : No substantial differences between SMAs and individual visits in terms of costs per QALY were found ( incremental cost-effectiveness ratio € −960.00 ; 95 % confidence interval € −34,600.00 , € + 36,800.00 ) . Sensitivity analyses showed that the cost-effectiveness ratio was particularly sensitive to SMA group size and proportion of patients seeing their treating neurologist . Conclusions : Cost-effectiveness of SMAs did not show a significant difference vs that of individual appointments based on data from our r and omized controlled trial . On the other h and , we were able to show that a minimum of 6 patients per SMA and 7 Output:

Compared to usual care , no negative effects on patient quality of life , knowledge and satisfaction were reported . Discussion Few rigorous studies evaluated the use of shared medical appointments for chronic illnesses . Overall , there appears to be no patient harms .

MS214164

***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 : 1 ) To investigate the comorbidity of verbal and nonverbal learning disability subtypes with several domains of behavior problems among 8-year-old children . 2 ) To determine whether receipt of an early intervention modified the association between childhood behavior problems and learning disabilities ( LD ) . Methods : This is a secondary data analysis of the Infant Health and Development Program ( IHDP ) , a r and omized clinical trial of an early intervention provided between ages 0 and 3 involving 985 children born low birthweight and premature . The findings are based on a prospect i ve follow-up of these children at 8 years of age . Results : Compared to children without verbal LD ( VLD ) , those with VLD were twice as likely to exhibit clinical levels of total behavior problems and 89 % more likely to exhibit externalizing behavior problems . Analysis of specific subscales of behavior revealed significant associations with anxious/depressed and withdrawn behaviors , as well as an increased likelihood of attention problems among children with VLD . No significant association was found between nonverbal LD ( NVLD ) and any type of behavior problem . Furthermore , there was a significant interaction between VLD and the intervention , in which the odds of internalizing behavior problems were greater among children with VLD . No interaction effect of the intervention occurred for any type of behavior problem among children with NVLD . Conclusions : These findings provide evidence that distinct differences exist for different learning disability subtypes with regards to behavioral outcomes and the effects of early intervention services among 8-year-old children A population -based , r and omized universal classroom intervention trial for the prevention of disruptive behavior ( i.e. , attention-deficit/hyperactivity problems , oppositional defiant problems , and conduct problems ) is described . Impact on developmental trajectories in young elementary schoolchildren was studied . Three trajectories were identified in children with high , intermediate , or low levels of problems on all 3 disruptive behaviors at baseline . The intervention had a positive impact on the development of all disruptive behavior problems in children with intermediate levels of these problems at baseline . Effect sizes of mean difference at outcome were medium or small . In children with the highest levels of disruptive behavior at baseline , a positive impact of the intervention was found for conduct problems A population -based r and omized intervention trial for the prevention of conduct problems ( i.e. , oppositional defiant disorder and conduct disorder ) is described . The LIFT ( Linking the Interests of Families and Teachers ) intervention was design ed for all first- and fifth- grade elementary school boys and girls and their families living in at-risk neighborhoods characterized by high rates of juvenile delinquency . The 10-week intervention strategy was carefully targeted at proximal and malleable antecedents in three social domains that were identified by a developmental model of conduct problems . From 12 elementary schools , 671 first and fifth grade rs and their families participated either in the theory-based universal preventive intervention or in a control condition . The intervention consisted of parent training , a classroom-based social skills program , a playground behavioral program , and systematic communication between teachers and parents . A multiple measure assessment strategy was used to evaluate participant satisfaction and participation , fidelity of implementation , and the immediate impacts of the program on targeted antecedents OBJECTIVE . To examine the extent to which the Early Start program of home visitation had beneficial consequences in the areas of maternal health , family functioning , family economic circumstances , and exposure to stress and adversity . METHODS . The study used a r and omized , controlled trial design in which 220 families receiving the Early Start program were contrasted with a control series of 223 families not receiving the program . Families were enrolled in the program after population screening conducted by community health nurses . Families were enrolled in the program for up to 36 months . Outcomes were assessed at 6 , 12 , 24 , and 36 months after trial entry . RESULTS . There was a consistent lack of association between maternal and family outcomes and group membership . There were no significant differences between the Early Start and control series in any comparisons . CONCLUSIONS . This evaluation suggested that the Early Start program failed to lead to parent- and family-related benefits . This absence of benefit for parent/family outcomes is contrasted with the benefits found previously for child-related outcomes , including child health , preschool education , child abuse and neglect , parenting , and behavioral adjustment . This comparison suggests that home visitation programs may provide benefits for child-related outcomes in the absence of parent- or family-related outcomes The outcomes of a r and omized clinical trial of a new behavioral family intervention , Stepping Stones Triple P , for preschoolers with developmental and behavior problems are presented . Forty-eight children with developmental disabilities participated , 27 r and omly allocated to an intervention group and 20 to a wait-list control group . Parents completed measures of parenting style and stress , and independent observers assessed parent-child interactions . The intervention was associated with fewer child behavior problems reported by mothers and independent observers , improved maternal and paternal parenting style , and decreased maternal stress . All effects were maintained at 6-month follow-up Aims : To assess the effectiveness of a parenting programme , delivered by health visitors in primary care , in improving the mental health of children and their parents among a representative general practice population . Methods : Parents of children aged 2–8 years who scored in the upper 50 % on a behaviour inventory were r and omised to the Webster-Stratton 10 week parenting programme delivered by trained health visitors , or no intervention . Main outcome measures were the Eyberg Child Behaviour Inventory and the Goodman Strengths and Difficulties Question naire to measure child behaviour , and the General Health Question naire , Abidin ’s Parenting Stress Index , and Rosenberg ’s Self Esteem Scale to measure parents ’ mental health . These outcomes were measured before and immediately after the intervention , and at six months follow up . Results : The intervention was more effective at improving some aspects of the children ’s mental health , notably conduct problems , than the no intervention control condition . The Goodman conduct problem score was reduced at immediate and six month follow up , and the Eyberg Child Behaviour Inventory was reduced at six months . The intervention also had a short term impact on social dysfunction among parents . These benefits were seen among families with children scoring in the clinical range for behaviour problems and also among children scoring in the non- clinical ( normal ) range . Conclusion : This intervention could make a useful contribution to the prevention of child behaviour problems and to mental health promotion in primary care This report describes the 3 year outcomes of three different variants of the Triple P-Positive Parenting Program , a behavioural family intervention . Families were r and omly assigned to one of three intervention conditions or to a waitlist condition . At 1 year follow-up there were similar improvements on observational and self-report measures of preschooler disruptive behaviour for Enhanced , St and ard and Self Directed variants of Triple P. At 3 year follow-up ( completed by 139 families ) , each condition showed a similar level of maintenance of intervention effects . Approximately 2/3 of preschoolers who were clinical ly elevated on measures of disruptive behaviour at pre-intervention moved from the clinical to the non- clinical range . Across conditions , there was a comparable preventive effect for each intervention for these high risk children . The implication s of the findings for the development of brief , cost effective parenting interventions within a public health framework are discussed OBJECTIVE Despite recognition of the need for parenting interventions to prevent childhood behavioral problems , few community programs have been evaluated . This report describes the r and omized controlled evaluation of a four-session psychoeducational group for parents of preschoolers with behavior problems , delivered in community agencies . METHOD In 1998 , 222 primary caregivers , recruited through community ads , filled out question naires on parenting practice s and child behavior . Parents were r and omly assigned to immediate intervention or a wait-list control . The intervention comprised three weekly group sessions and a 1-month booster , the focus being to support effective discipline ( using the video 1 - 2 - 3 Magic ) and to reduce parent-child conflict . RESULTS Using an intent-to-treat analysis , repeated- measures analyses of variance indicated that the parents who received the intervention reported significantly greater improvement in parenting practice s and a significantly greater reduction in child problem behavior than the control group . The gains in positive parenting behaviors were maintained at 1-year follow-up in a subset of the experimental group . CONCLUSIONS This brief intervention program may be a useful first intervention for parents of young children with behavior problems , as it seems both acceptable and reasonably effective OBJECTIVE To determine if a home-based nurse intervention ( INT ) , focusing on parenting education/skills and caregiver emotional support , reduces child behavioral problems and parenting stress in caregivers of in utero drug-exposed children . DESIGN R and omized clinical trial of a home-based INT . SETTING S Two urban hospital newborn nurseries ; homes of infants ( the term infant is used interchangeably in this study with the term child to denote those from birth to the age of 36 months ) ; and a research clinic in Baltimore , Md. PARTICIPANTS In utero drug-exposed children and their caregivers ( N = 100 ) were examined when the child was between the ages of 2 and 3 years . Two groups were studied : st and ard care ( SC ) ( n = 51 ) and INT ( n = 49 ) . INTERVENTION A home nurse INT consisting of 16 home visits from birth to the age of 18 months to provide caregivers with emotional support and parenting education and to provide health monitoring for the infant . MAIN OUTCOME MEASURES Scores on the Child Behavior Checklist and the Parenting Stress Index . RESULTS Significantly more drug-exposed children in the SC group earned t scores indicative of significant emotional or behavioral problems than did children in the INT group on the Child Behavior Checklist Total ( 16 [ 31 % ] vs 7 [ 14 % ] ; P = .04 ) , Externalizing ( 19 [ 37 % ] vs 8 [ 16 % ] ; P = .02 ) , and Internalizing ( 14 [ 27 % ] vs. 6 [ 12 % ] ; P = .05 ) scales and on the anxiety-depression subscale ( 16 [ 31 % ] vs. 5 [ 10 % ] ; P = .009 ) . There was a trend ( P = .06 ) in more caregivers of children in the SC group reporting higher parenting distress than caregivers of children in the INT group . CONCLUSIONS In utero drug-exposed children receiving a home-based nurse INT had significantly fewer behavioral problems than did in utero drug-exposed children receiving SC ( P = .04 ) . Furthermore , those caregivers receiving the home-based INT reported a trend toward lower total parenting distress compared with caregivers of children who received SC with no home visits This article describes a 20-year program of research on the Nurse Home Visitation Program , a model in which nurses visit mothers beginning during pregnancy and continuing through their children 's second birthdays to improve pregnancy outcomes , to promote children 's health and development , and to strengthen families ' economic self-sufficiency . The results of two r and omized trials ( one in Elmira , New York , and the second in Memphis , Tennessee ) are summarized , and an ongoing trial in Denver , Colorado , is briefly described . Results of the Elmira and Memphis trials suggest the following : The program benefits the neediest families ( low-income unmarried women ) but provides little benefit for the broader population . Among low-income unmarried women , the program helps reduce rates of childhood injuries and ingestions that may be associated with child abuse and neglect , and helps mothers defer subsequent pregnancies and move into the workforce . Long-term follow-up of families in Elmira indicates that nurse-visited mothers were less likely to abuse or neglect their children or to have rapid successive pregnancies . Having fewer children enabled women to find work , become economically self-sufficient , and eventually avoid substance abuse and criminal behavior . Their children benefitted too . By the time the children were 15 years of age , they had had fewer arrests and convictions , smoked and drank less , and had had fewer sexual partners . The program produced few effects on children 's development or on birth outcomes , except for children born to women who smoked cigarettes when they registered during pregnancy . The positive effects of the program on child abuse and injuries to children were most pronounced among mothers who , at registration , had the lowest psychological re sources ( defined as high levels of mental health symptoms , limited intellectual functioning , and little belief in their control of their lives ) . Generally , effects in Elmira were of greater magnitude and covered a broader range of outcomes than in Memphis , perhaps because of differences between the population s studied , community context s , or a higher rate of turnover among home visitors in Memphis than in Elmira . The article concludes that the use of nurses as home visitors is key ; that services should be targeted to the neediest population s , rather than being offered on a universal basis ; that clinical ly tested methods of changing health and behavioral risks should be incorporated into program protocol s ; and that services must be implemented with fidelity to the model tested if program benefits found in scientifically controlled studies are to be reproduced as the program is replicated in new communities Aims : To test the effectiveness at one year of the Webster Stratton Parents and Children Series group parenting programme in a population sample of parents . Methods : In a multicentre block r and omised controlled trial , parents of children aged 2–8 years in 116 families who scored in the upper 50 % on a vali date d behaviour inventory , took part in Webster-Stratton ’s 10 week parenting programme led by trained and supervised health visitors . The following outcome measures were used : Eyberg Child Behaviour Inventory , Goodman Strengths and Difficulties Question naire , General Health Question naire , Parenting Stress Index , Rosenberg Self Esteem Scale . Results : The intervention significantly reduced child behaviour problems and improved mental health at immediate and 6 month follow ups . One year differences between control and intervention groups were not significant . Qualitative results suggest that these findings might be attributable in part to either Hawthorne effects or contamination of control group . At interview parents described ways in which the programme had improved their mental health . They reported g Output:

Effective preventive interventions exist primarily for behaviour and , to a lesser extent , emotional problems , and could be disseminated from research to mainstream in Australia , ensuring fidelity to original programmes .

MS214165

***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: Nuclear factor-kappaB ( NF-kappaB ) and glucocorticoid receptor-alpha ( GR-alpha ) have diametrically opposed functions in regulating inflammation . We investigated whether unresolving acute respiratory distress syndrome ( ARDS ) is associated with systemic inflammation- induced glucocorticoid resistance and whether prolonged methylprednisolone administration accelerates the suppression of systemic inflammatory indices and normalizes the sensitivity of the immune system to glucocorticoids . Patients enrolled into a r and omized trial evaluating prolonged methylprednisolone administration in unresolving ARDS had serial plasma sample s collected before and after r and omization . In the plasma , we measured the concentrations of tumor necrosis factor-alpha ( TNF-alpha ) , interleukins ( IL ) IL-1beta and IL-6 , adrenocorticotropic hormone ( ACTH ) , and cortisol . The ability of patient plasma to influence the NF-kappaB and GR-signal transduction systems of normal peripheral blood leukocytes ( PBL ) was examined . Patients treated with methylprednisolone had progressive and sustained reductions of TNF-alpha , IL-1beta , IL-6 , ACTH , and cortisol concentrations over time . Normal PBL exposed to plasma sample s collected during methylprednisolone exhibited significant progressive increases in all aspects of GR-mediated activity and significant reductions in NF-kappaB DNA-binding and transcription of TNF-alpha and IL-1beta . These findings provide support for the presence of endogenous glucocorticoid inadequacy in the control of inflammation and systemic inflammation-induced peripheral glucocorticoid resistance in ARDS . Prolonged methylprednisolone administration accelerated the resolution of both systemic inflammation and peripheral acquired glucocorticoid resistance in ARDS ACTH stimulation is the st and ard test for assessment of adrenal function . It was suggested that the low dose ( 1 microg ) would be more sensitive for detecting mild secondary adrenal insufficiency than the usual dose of 250 microg . The aim of this study was to find the optimal diagnostic criteria and to compare st and ard dose test ( SDT ) with the low dose test ( LDT ) . A group of patients treated with corticosteroids for the 6 months was considered to have hypothalamo-pituitary-adrenal impairment . Studies were performed in 14 corticosteroid-treated and 28 control subjects in r and om order on 2 consecutive days . Tests were analyzed using the receiver operating characteristic curve method . The best test was cortisol increment at 15 min of the LDT . It was significantly better than the cortisol concentration at 15 min of the SDT , the best test during the SDT ( receiver operating characteristic curve area and 95 % confidence interval : LDT , 0.997 and 0.956 - 0.999 ; SDT , 0.827 and 0.662 - 0.929 ; P = 0.0113 ) . For the cortisol increment at 15 min of the LDT at 100 % sensitivity , the diagnostic value was 100 mmol/L , and the specificity was 96 % . Therefore , the LDT is superior to the st and ard dose test in the assessment of secondary adrenal insufficiency BACKGROUND Exposure to intense physical and psychological stress during septic shock can result in posttraumatic stress disorder in survivors . Patients with chronic posttraumatic stress disorder often show sustained reductions in serum cortisol concentration . This investigation examines whether increasing serum cortisol levels with hydrocortisone treatment during septic shock reduces the incidence of posttraumatic stress disorder in survivors . METHODS Patients ( n = 20 ) were recruited from a prospect i ve , r and omized double-blind study on the hemodynamic effects of hydrocortisone during septic shock . Eleven patients had received placebo and nine stress doses of hydrocortisone . Posttraumatic stress disorder was diagnosed 31 months ( median ) after intensive care unit discharge using SCID-IV ( DSM-IV- criteria ) . Furthermore , the number of categories of traumatic memory from ICU treatment was determined in both groups at that time . RESULTS Only one of nine patients from the hydrocortisone group developed posttraumatic stress disorder , compared with seven of 11 patients in the placebo group ( p = .02 ) . There was no significant difference with regard to the number of categories of traumatic memory between the hydrocortisone and placebo groups . CONCLUSIONS The administration of hydrocortisone during septic shock in a dosage similar to the endogenous maximal production rate was associated with a lower incidence of posttraumatic stress disorder in long-term survivors , which seems to be independent of the number of categories of traumatic memory Abstract . Objective : To study the time course of corticosteroid binding-globulin ( CBG ) level and the free cortisol index ( FCI ) in comparison with total cortisol and ACTH concentrations during acute and prolonged critical illness . Design : Prospect i ve observational clinical study . Setting : Twenty-bed medical/surgical intensive care unit . Patients and participants : Thirty patients with septic shock , eight patients with multitrauma , and forty healthy control subjects . Measurements and results : During 14 days or until discharge/death , we serially measured serum concentrations of CBG , cortisol , TNF-α , IL-6 , plasma ACTH immunoreactivity , and the FCI ( = cortisol/CBG × 100 ) . We also recorded haemodynamic parameters , APACHE II , ISS , SOFA scores , shock duration , inotrope use , and ICU mortality . In both groups we found markedly decreased CBG levels in the early phase ( septic shock : 17.5±5.9 , and trauma : 16.1±2.3 mg/l ) in comparison with controls ( 37.3±5.3 mg/l ) . The FCI was high in this early phase ( septic shock : 7.2±2.7 ; trauma : 6.5±1.3 ; controls : 1.25±0.76 ) . During follow-up , CBG levels significantly increased , reaching normal levels from day 7 on . The FCI showed an opposite biphasic pattern , with near-normalising FCI values during the second phase . Regression analysis showed a negative correlation between CBG and IL-6 levels ( rs=–0.63 ; P<0.05 ) , but no relation between CBG concentrations and disease severity , shock duration or death was found . Conclusions : We found extremely low CBG levels in early stage septic shock and multitrauma . These dramatic changes are reflected in a concomitant higher FCI , indicating a higher free cortisol level . A second phase displays increasing and normalising CBG levels , independent from clinical parameters . We believe that CBG plays an active role in the glucocorticoid response to severe stress and in the regulation of cortisol availability to target tissues Objective To investigate , in patients with severe septic shock , the adrenocortical function assessed by daily plasma cortisol determinations during the first 72 h and by the short synthetic ACTH stimulation test performed within 24 h of the onset of shock . Design Prospect i ve clinical investigation . Setting Medical intensive care unit in a university teaching hospital . Patients 40 consecutive patients with documented septic shock requiring at least hemodynamic resuscitation and respiratory support . Interventions There were no intervention . Measurements and results Basal cortisol concentrations were increased with a mean value of 36.8 μg/dl ( range 7.9–113 ) . Of the overall cortisol determinations 92 % were above 15 μg/dl . No statistically significant differences in basal cortisol concentrations were found when survival , type of infection , and positive blood cultures were considered . Patients with hepatic disease had significantly higher cortisol ( 50.1(±6.2 ) μ/dl versus 35.9(±3.3 ) μg/dl , p=0.035 ) levels compared to other patients . No correlations were found between basal plasma cortisol concentrations and factors such as SAPS , OSF , hemodynamic measurements , duration of shock , and amount of vasopressor and /or inotropic agents . Cortisol concentrations had significant but weak correlation with ACTH levels in survivors ( r=0.4;p=0.03;n=28 ) but not in non-survivors ( r=0.03;p=0.85;n=52 ) . Cortisol levels in non-survivors increased significantly from enrollment time to the 72nd hour of the survey ( day 1 : 38.9(±3.8 ) μg/dl versus day 3 : 66.7(±17.1 ) μg/dl;p=0.046 ) and were significantly higher than those recorded in survivors . Responses to the short ACTH stimulation test were not significantly different between survivors and non-survivors . According to the different criteria used to interpret the response to the ACTH stimulation test , incidence of adrenocortical insufficiency was highly variable ranging from 6.25–75 % in patients with septic shock . Only one patient had absolute adrenocortical insufficiency ( basal cortisol level below 10 μg/dl ; response to the ACTH stimulation test below 18 μg/dl . Conclusion Our data suggest that in a selected population of patients with severe septic shock single plasma cortisol determination has no predictive value . The short ACTH stimulation test performed within the first 24 h of onset shock can neither predict outcome nor estimate impairment in adrenocortical function in patients with high basal cortisol level . Adrenal insufficiency is rare in septic shock and should be suspected when cortisol level is below 15 μg/dl and then confirmed by a peak cortisol level lower than 18 μg/dl during the short ACTH stimulation test CONTEXT The hypothalamic-pituitary-adrenal axis is a major determinant of the host response to stress . The relationship between its activation and patient outcome is not known . OBJECTIVE To evaluate the prognostic value of cortisol levels and a short corticotropin stimulation test in patients with septic shock . DESIGN AND SETTING Prospect i ve inception cohort study conducted between October 1991 and September 1995 in 2 teaching hospital adult intensive care units in France . PARTICIPANTS A total of 189 consecutive patients who met clinical criteria for septic shock . INTERVENTION A short corticotropin stimulation test was performed in all patients by intravenously injecting 0.25 mg of tetracosactrin ; blood sample s were taken immediately before the test ( T0 ) and 30 ( T30 ) and 60 ( T60 ) minutes afterward . MAIN OUTCOME MEASURES Twenty-eight-day mortality as a function of variables collected at the onset of septic shock , including cortisol levels before the corticotropin test and the cortisol response to corticotropin ( delta max , defined as the difference between T0 and the highest value between T30 and T60 ) . RESULTS The 28-day mortality was 58 % ( 95 % confidence interval [ CI ] , 51%-65 % ) and median time to death was 17 days ( 95 % CI , 14 - 27 days ) . In multivariate analysis , independent predictors of death ( P < or = .001 for all ) were McCabe score greater than 0 , organ system failure score greater than 2 , arterial lactate level greater than 2.8 mmol/L , ratio of PaO2 to fraction of inspired oxygen no more than 160 mm Hg , cortisol level at T0 greater than 34 microg/dL and delta max no more than 9 microg/dL. Three groups of patient prognoses were identified : good ( cortisol level at T0 < or = 34 microg/dL and delta max > 9 microg/dL ; 28-day mortality rate , 26 % ) , intermediate ( cortisol level at T0 34 microg/dL and delta max < or = 9 microg/dL or cortisol level at T0 > 34 microg/dL and delta max > 9 microg/dL ; 28-day mortality rate , 67 % ) , and poor ( cortisol level at T0 > 34 microg/dL and delta max < or = 9 microg/dL ; 28-day mortality rate , 82 % ) . CONCLUSION Our data suggest that a short corticotropin test has a good prognostic value and could be helpful in identifying patients with septic shock at high risk for death BACKGROUND Preliminary reports suggest that patients with the acquired immunodeficiency syndrome ( AIDS ) and Pneumocystis carinii pneumonia may benefit from the addition of corticosteroid treatment to antibiotic therapy . METHODS We conducted a double-blind , placebo-controlled trial to assess the efficacy of adjunctive corticosteroids in patients with AIDS and severe P. carinii pneumonia . Patients with marked abnormalities in gas exchange who had been treated with antibiotics for less than 72 hours were r and omly assigned to receive either methylprednisolone ( 40 mg ) or placebo every 6 hours for 7 days , in addition to treatment for 21 days with trimethoprim-sulfamethoxazole . The primary outcome measures were survival until hospital discharge and the development of respiratory failure . RESULTS Twenty-three patients were enrolled in the study ; there were no significant differences in base-line clinical or laboratory measures between the two treatment groups . Of 12 patients treated with corticosteroids , 9 ( 75 percent ) survived until hospital Output:

Low doses of corticosteroids are recommended in patients with septic shock . In the absence of vasopressor requirement , corticosteroids should not be used to treat sepsis . High-dose corticosteroids are not recommended in severe sepsis .

MS214166

***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 Malaria control in Africa is most tractable in urban settlements yet most research has focused on rural setting s. Elimination of malaria transmission from urban areas may require larval control strategies that complement adult mosquito control using insecticide-treated nets or houses , particularly where vectors feed outdoors . Methods and Findings Microbial larvicide ( Bacillus thuringiensis var . israelensis ( Bti ) ) was applied weekly through programmatic , non-r and omized community-based , but vertically managed , delivery systems in urban Dar es Salaam , Tanzania . Continuous , r and omized cluster sampling of malaria infection prevalence and non-r and om programmatic surveillance of entomological inoculation rate ( EIR ) respectively constituted the primary and secondary outcomes surveyed within a population of approximately 612,000 residents in 15 fully urban wards covering 55 km2 . Bti application for one year in 3 of those wards ( 17 km2 with 128,000 residents ) reduced crude annual transmission estimates ( Relative EIR [ 95 % Confidence Interval ] = 0.683 [ 0.491–0.952 ] , P = 0.024 ) but program effectiveness peaked between July and September ( Relative EIR [ CI ] = 0.354 [ 0.193 to 0.650 ] , P = 0.001 ) when 45 % ( 9/20 ) of directly observed transmission events occurred . Larviciding reduced malaria infection risk among children ≤5 years of age ( OR [ CI ] = 0.284 [ 0.101 to 0.801 ] , P = 0.017 ) and provided protection at least as good as personal use of an insecticide treated net ( OR [ CI ] = 0.764 [ 0.614–0.951 ] , P = 0.016 ) . Conclusions In this context , larviciding reduced malaria prevalence and complemented existing protection provided by insecticide-treated nets . Larviciding may represent a useful option for integrated vector management in Africa , particularly in its rapidly growing urban centres The study was conducted in eight adjacent villages in central Sri Lanka where there are many shallow pits dug by gem miners that fill with water . These become breeding places of the main malarial vector Anopheles culicifacies , and of the second most important vector Anopheles subpictus , but not of Anopheles varuna , the third most important vector . With the help of local volunteers , data on the adult population s of these three species was collected by various st and ard methods , and data on the incidence of malaria cases was collected by two clinics set up for the project and through the existing hospitals . Prevalence of malaria infection in symptom-less people was investigated by mass blood surveys . On the basis of a year 's pre-intervention data the villages were stratified into four with high levels of malaria transmission and four with lower transmission . Within each stratum two villages were r and omly assigned for mosquito control by treating all the gem pits , as well as river bed pools , with a granular formulation of the insect growth regulator pyriproxyfen at a target dose of 0.01 mg a.i./litre . The intervention caused significant reductions in the adult population s of An . culicifacies and An . subpictus . Similarly , incidence of malaria was reduced in the intervention villages to about 24 % ( 95 % c.l . 20 - 29 % ) of that in the controls . Prevalence of parasitaemia also declined significantly . It is concluded that in this situation where , with active community participation , the breeding sites of the main vectors could be located ; vector control by a highly active and persistent insect growth regulator can be a very effective means of malaria control The relationship between malaria transmission intensity and efficiency is important for malaria epidemiology , for the design of r and omized control trials that measure transmission or incidence as end points , and for measuring and modelling malaria transmission and control . Five kinds of studies published over the past century were assembled and reanalysed to quantify malaria transmission efficiency and describe its relation to transmission intensity , to underst and the causes of inefficient transmission and to identify functions suitable for modelling mosquito-borne disease transmission . In this study , we show that these studies trace a strongly nonlinear relationship between malaria transmission intensity and efficiency that is parsimoniously described by a model of heterogeneous biting . When many infectious bites are concentrated on a few people , infections and parasite population structure will be highly aggregated affecting the immunoepidemiology of malaria , the evolutionary ecology of parasite life history traits and the measurement and stratification of transmission for control using entomological and epidemiological data An evaluation of pyriproxyfen as a larval control agent with the aim of reducing malaria vector population s and incidence of malaria was conducted in 12 villages in an irrigated settlement scheme in the dry zone of central Sri Lanka . In these villages , there are many pools in the beds of rivers , streams , and irrigation ditches during the dry season of the year . These are the major breeding places of the malaria vectors Anopheles culicifacies and An . subpictus . Collection s of adult mosquitoes were carried out by using st and ard methods and parasitological data were collected by daily malaria clinics set up for the project and through the 2 government hospitals . All villages in the study area were under residual house spraying with lambdacyhalothrin water-dispersible powder . Using the 1st year 's baseline data collection , the villages were stratified into 6 villages with high malaria incidence and 6 villages with low incidence . Within each group , 3 villages were r and omly assigned for larval control by treating all the pools in the beds of rivers , streams , and irrigation ditches and agricultural wells with a granular formulation of the insect growth regulator pyriproxyfen at the rate of 0.01 mg active ingredient/liter . The field bioassays indicated that a single treatment of pyriproxyfen effectively inhibited the emergence of adult mosquitoes in the riverbed pools for a period of 190 days . The treatment caused significant reduction of the adult population s of An . culicifacies ( 78 % ) and An . subpictus ( 72 % ) . Similarly , incidence of malaria was reduced in the treatment villages by about 70 % ( 95 % confidence interval 58 - 78 % ) compared with the controls . The conclusion is made that pyriproxyfen can be a very effective means of malaria control if all possible vector breeding places in the area can be located Output:

In Africa and Asia , LSM is another policy option , alongside LLINs and IRS , for reducing malaria morbidity in both urban and rural areas where a sufficient proportion of larval habitats can be targeted .

MS214167

***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 the efficacy of fluid resuscitation as guided by lactate clearance rate ( LCR ) and central venous oxygen saturation ( ScvO2 ) in patients with sepsis . METHODS A prospect i ve r and omized control study was conducted . Fifty patients diagnosed with severe sepsis or septic shock from January 2011 to February 2012 in department of critical care medicine of Fourth Hospital of Hebei Medical University were enrolled in the study . The patients were r and omly divided into two groups according to the sequence ( each n=25 ) : ScvO2 group and LCR group . After ICU admission , the patients were treated symptomatically timely , and fluid resuscitation was started as early as possible according to Surviving Sepsis Campaign guidance for management of severe sepsis and septic shock 2008 . Central venous pressure (CVP)≥8 mm Hg ( 1 mm Hg=0.133 kPa ) , mean arterial pressure (MAP)≥65 mm Hg and ScvO2≥0.70 served as goal values to accomplish the fluid resuscitation therapy in ScvO2 group , while CVP≥8 mm Hg , MAP≥65 mm Hg , LCR≥10 % served as goal value to accomplish the fluid resuscitation therapy in LCR group . The general condition and clinical characteristics on arrival in ICU , changes in CVP , MAP , ScvO2 , lactate level and /or LCR before ( 0 hour ) and 3 , 6 , 72 hours after the start of fluid resuscitation and the other related conditions during the therapy were recorded . RESULTS There was no significant difference in general data or clinical characteristics before the start of therapy , occurrence of organ dysfunction , or treatment measures during different time periods after start of fluid resuscitation . Compared with the condition immediately before fluid resuscitation , at 3 hours after start of fluid resuscitation , CVP were improved in LCR and ScvO2 groups ( 8.58±1.17 mm Hg vs. 6.33±1.21 mm Hg , 9.08±2.43 mm Hg vs. 5.33±0.98 mm Hg , both P<0.05 ) ; at 6 hours after start of fluid resuscitation , heart rate ( HR ) and respiratory rate ( RR ) were lowered in LCR and ScvO2 groups ( HR : 96±18 bpm vs. 127±13 bpm , 98±13 bpm vs. 116±19 bpm , RR : 23±3 times/min vs. 33±9 times/min , 24±5 times/min vs. 35±6 times/min , all P<0.05 ) , oxygenation index ( PaO2/FiO2 ) was increased in LCR and ScvO2 groups ( 179±41 mm Hg vs. 86±21 mm Hg , 202±33 mm Hg vs. 95±17 mm Hg , both P<0.05 ) , and there was no significant difference in MAP in both groups . There was no significant difference in all indexes between two groups . In LCR group , 3 hours after start of fluid resuscitation , lactate level was significantly decreased ( 2.81±0.18 mmol/L vs. 3.43±1.31 mmol/L , P<0.05 ) . Compared with the value 3 hours after start of fluid resuscitation , LCR was significantly improved at 6 hours and 72 hours after start of fluid resuscitation in LCR group [ (42.69±8.75)% , (48.87±9.69)% vs. (20.32±4.58)% , both P<0.05 ] . Compared with that immediately before fluid resuscitation , ScvO2 was significant improved in ScvO2 group at 3 hours after start of fluid resuscitation ( 0.65±0.04 vs. 0.53±0.06 , P<0.05 ) . There was no significant difference in success rate of fluid resuscitation comparing that of 6 hours and that of 72 hours [ 6 hours : 72 % ( 18/25 ) vs. 64 % ( 16/25 ) , χ(2)=0.368 , P=0.762 ; 72 hours : 88 % ( 22/25 ) vs. 88 % ( 22/25 ) , χ(2)=0.000 , P=1.000 ] , length of ICU stay ( 8±3 days vs. 10±4 days , t=0.533 , P=0.874 ) , length of hospital stay ( 29±11 days vs. 35±16 days , t=0.692 , P=0.531 ) , improvement rate [ 84 % ( 21/25 ) vs. 76%(19/25 ) , χ(2)=0.500 , P=0.480 ] or 28-day mortality [ 20 % ( 5/25 ) vs. 28 % ( 7/25 ) , χ(2)=0.439 , P=0.742 ] between LCR and ScvO2 groups . CONCLUSIONS Both LCR and ScvO2 can be taken as the index in confirming the endpoint of fluid resuscitation for patients with severe sepsis and septic shock . Fluid resuscitation therapy under the guidance of LCR is accurate and reliable in patients with severe sepsis and septic shock BACKGROUND In a single-center study published more than a decade ago involving patients presenting to the emergency department with severe sepsis and septic shock , mortality was markedly lower among those who were treated according to a 6-hour protocol of early goal -directed therapy ( EGDT ) , in which intravenous fluids , vasopressors , inotropes , and blood transfusions were adjusted to reach central hemodynamic targets , than among those receiving usual care . We conducted a trial to determine whether these findings were generalizable and whether all aspects of the protocol were necessary . METHODS In 31 emergency departments in the United States , we r and omly assigned patients with septic shock to one of three groups for 6 hours of resuscitation : protocol -based EGDT ; protocol -based st and ard therapy that did not require the placement of a central venous catheter , administration of inotropes , or blood transfusions ; or usual care . The primary end point was 60-day in-hospital mortality . We tested sequentially whether protocol -based care ( EGDT and st and ard-therapy groups combined ) was superior to usual care and whether protocol -based EGDT was superior to protocol -based st and ard therapy . Secondary outcomes included longer-term mortality and the need for organ support . RESULTS We enrolled 1341 patients , of whom 439 were r and omly assigned to protocol -based EGDT , 446 to protocol -based st and ard therapy , and 456 to usual care . Resuscitation strategies differed significantly with respect to the monitoring of central venous pressure and oxygen and the use of intravenous fluids , vasopressors , inotropes , and blood transfusions . By 60 days , there were 92 deaths in the protocol -based EGDT group ( 21.0 % ) , 81 in the protocol -based st and ard-therapy group ( 18.2 % ) , and 86 in the usual-care group ( 18.9 % ) ( relative risk with protocol -based therapy vs. usual care , 1.04 ; 95 % confidence interval [ CI ] , 0.82 to 1.31 ; P=0.83 ; relative risk with protocol -based EGDT vs. protocol -based st and ard therapy , 1.15 ; 95 % CI , 0.88 to 1.51 ; P=0.31 ) . There were no significant differences in 90-day mortality , 1-year mortality , or the need for organ support . CONCLUSIONS In a multicenter trial conducted in the tertiary care setting , protocol -based resuscitation of patients in whom septic shock was diagnosed in the emergency department did not improve outcomes . ( Funded by the National Institute of General Medical Sciences ; ProCESS Clinical Trials.gov number , NCT00510835 . ) BACKGROUND Early goal -directed therapy ( EGDT ) has been endorsed in the guidelines of the Surviving Sepsis Campaign as a key strategy to decrease mortality among patients presenting to the emergency department with septic shock . However , its effectiveness is uncertain . METHODS In this trial conducted at 51 centers ( mostly in Australia or New Zeal and ) , we r and omly assigned patients presenting to the emergency department with early septic shock to receive either EGDT or usual care . The primary outcome was all-cause mortality within 90 days after r and omization . RESULTS Of the 1600 enrolled patients , 796 were assigned to the EGDT group and 804 to the usual-care group . Primary outcome data were available for more than 99 % of the patients . Patients in the EGDT group received a larger mean ( ±SD ) volume of intravenous fluids in the first 6 hours after r and omization than did those in the usual-care group ( 1964±1415 ml vs. 1713±1401 ml ) and were more likely to receive vasopressor infusions ( 66.6 % vs. 57.8 % ) , red-cell transfusions ( 13.6 % vs. 7.0 % ) , and dobutamine ( 15.4 % vs. 2.6 % ) ( P<0.001 for all comparisons ) . At 90 days after r and omization , 147 deaths had occurred in the EGDT group and 150 had occurred in the usual-care group , for rates of death of 18.6 % and 18.8 % , respectively ( absolute risk difference with EGDT vs. usual care , -0.3 percentage points ; 95 % confidence interval , -4.1 to 3.6 ; P=0.90 ) . There was no significant difference in survival time , in-hospital mortality , duration of organ support , or length of hospital stay . CONCLUSIONS In critically ill patients presenting to the emergency department with early septic shock , EGDT did not reduce all-cause mortality at 90 days . ( Funded by the National Health and Medical Research Council of Australia and the Alfred Foundation ; ARISE Clinical Trials.gov number , NCT00975793 . ) CONTEXT Goal -directed resuscitation for severe sepsis and septic shock has been reported to reduce mortality when applied in the emergency department . OBJECTIVE To test the hypothesis of noninferiority between lactate clearance and central venous oxygen saturation ( ScvO2 ) as goals of early sepsis resuscitation . DESIGN , SETTING , AND PATIENTS Multicenter r and omized , noninferiority trial involving patients with severe sepsis and evidence of hypoperfusion or septic shock who were admitted to the emergency department from January 2007 to January 2009 at 1 of 3 participating US urban hospitals . INTERVENTIONS We r and omly assigned patients to 1 of 2 resuscitation protocol s. The ScvO2 group was resuscitated to normalize central venous pressure , mean arterial pressure , and ScvO2 of at least 70 % ; and the lactate clearance group was resuscitated to normalize central venous pressure , mean arterial pressure , and lactate clearance of at least 10 % . The study protocol was continued until all goals were achieved or for up to 6 hours . Clinicians who subsequently assumed the care of the patients were blinded to the treatment assignment . MAIN OUTCOME MEASURE The primary outcome was absolute in-hospital mortality rate ; the noninferiority threshold was set at Delta equal to -10 % . RESULTS Of the 300 patients enrolled , 150 were assigned to each group and patients were well matched by demographic , comorbidities , and physiological features . There were no differences in treatments administered during the initial 72 hours of hospitalization . Thirty-four patients ( 23 % ) in the ScvO2 group died while in the hospital ( 95 % confidence interval [ CI ] , 17%-30 % ) compared with 25 ( 17 % ; 95 % CI , 11%-24 % ) in the lactate clearance group . This observed difference between mortality rates did not reach the predefined -10 % threshold ( intent-to-treat analysis : 95 % CI for the 6 % difference , -3 % to 15 % ) . There were no differences in treatment-related adverse events between the groups . CONCLUSION Among patients with septic shock who were treated to normalize central venous and mean arterial pressure , additional management to normalize lactate clearance compared with management to normalize ScvO2 did not result in significantly different in-hospital mortality . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00372502 BACKGROUND Early , goal -directed therapy ( EGDT ) is recommended in international guidelines for the resuscitation of patients presenting with early septic shock . However , adoption has been limited , and uncertainty about its effectiveness remains . METHODS We conducted a pragmatic r and omized trial with an integrated cost-effectiveness analysis in 56 hospitals in Engl and . Patients were r and omly assigned to receive either EGDT ( a 6-hour resuscitation protocol ) or usual care . The primary clinical outcome was all-cause mortality at 90 days . RESULTS We enrolled 1260 patients , with 630 assigned to EGDT and 630 to usual care . By 90 days , 184 of 623 patients ( 29.5 % ) in the EGDT group and 1 Output:

Conclusion EGDT is not superior to usual care for ED patients with septic shock but is associated with increased utilisation of ICU re sources

MS214168

***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 Intermittent oral or intravenous doses of calcitriol given two or three times per week are commonly used to treat secondary hyperparathyroidism ( secondary HPT ) . This study was undertaken to compare the biochemical and skeletal responses to thrice weekly intraperitoneal ( i.p . ) versus oral doses of calcitriol in children with secondary HPT undergoing peritoneal dialysis ( CCPD ) . METHODS Forty-six patients aged 12.5+/-4.8 years on CCPD for 22+/-25 months were r and omly assigned to treatment with oral ( p.o . ) or i.p . calcitriol for 12 months ; 17 subjects given p.o . calcitriol and 16 subjects given i.p . calcitriol completed the study . Bone biopsies were performed at the beginning and at the end of the study , while determinations of serum and total ionized calcium , phosphorus , alkaline phosphatase , parathyroid hormone ( PTH ) and calcitriol levels were done monthly . RESULTS Serum total and ionized calcium levels were higher in subjects treated with i.p . calcitriol , P < 0.0001 , whereas serum phosphorus levels were higher in those given p.o . calcitriol , P < 0.0001 . For the i.p . group , serum PTH levels decreased from pre-treatment values of 648+/-125 pg/ml to a nadir of 169+/-57 pg/ml after nine months . In contrast , serum PTH levels did not change from baseline values of 670+/-97 pg/ml in subjects given p.o . calcitriol , P < 0.0001 by multiple regression analysis . Serum alkaline phosphatase levels were also lower in patients treated with i.p . calcitriol , P < 0.0001 , but there was no difference between groups in the average dose of calcitriol given thrice weekly . The skeletal lesions of secondary HPT improved in both groups , 33 % of patients developed adynamic bone lesion . CONCLUSION Differences in the bioavailability of calcitriol and /or in phosphorus metabolism may account for the divergent biochemical response to p.o . and i.p . calcitriol Amino-terminally truncated parathyroid hormone ( PTH ) fragments are detected to differing degrees by first- and second-generation immunometric PTH assays ( PTH-IMAs ) , and acute changes in serum calcium affect the proportion of these fragments in circulation . However , the effect of chronic calcium changes and different vitamin D doses on these PTH measurements remains to be defined . In this study , 60 pediatric dialysis patients , aged 13.9 ± 0.7 years , with secondary hyperparathyroidism were r and omized to 8 months of therapy with oral vitamin D combined with either calcium carbonate ( CaCO3 ) or sevelamer . Serum phosphorus levels did not differ between groups . Serum calcium levels rose from 9.3 ± 0.1 to 9.7 ± 0.1 mg/dl during CaCO3 therapy ( p < 0.01 from baseline ) but remained unchanged during sevelamer therapy . In the CaCO3 and sevelamer groups , baseline serum PTH levels ( 1st PTH-IMA ; Nichols Institute Diagnostics , San Clemente , CA ) were 964 ± 75 and 932 ± 89 pg/ml , and levels declined to 491 ± 55 and 543 ± 59 pg/ml , respectively ( nonsignificant between groups ) . Patients treated with sevelamer received higher doses of vitamin D than those treated with CaCO3 . The PTH values obtained by first- and second-generation PTH-IMAs correlated closely throughout therapy and the response of PTH was similar to both PTH-IMAs , despite differences in serum calcium levels BACKGROUND Oral and intravenous calcitriol bolus therapy are both recommended for the treatment of secondary hyperparathyroidism , but it has been cl aim ed that the latter is less likely to induce absorptive hypercalcemia . The present study was undertaken to verify whether intravenous calcitriol actually stimulates intestinal calcium absorption less than oral calcitriol and whether it is superior in suppressing parathyroid hormone ( PTH ) secretion . METHODS Twenty children ( 16 males , age range of 5.1 to 16.9 years , mean creatinine clearance 21.9 + /- 11.5 mL/min/1.73 m2 , range of 7.4 to 52.7 ) with chronic renal failure ( CRF ) and secondary hyperparathyroidism [ median intact PTH ( iPTH ) , 327 pg/mL ; range 143 to 1323 ] received two single calcitriol boli ( 1.5 mg/m2 body surface area ) orally and intravenously using a r and omized crossover design . iPTH and 1,25(OH)2D3 levels were measured over 72 hours , and intestinal calcium absorption was measured 24 hours after the calcitriol bolus using stable strontium ( Sr ) as a surrogate marker . Baseline control values for Sr absorption were obtained in a separate group of children with CRF of similar severity . RESULTS The peak serum level of 1,25(OH)2D3 and area under the curve baseline to 72 hours ( AUC0 - 72h ) were significantly higher after intravenous ( IV ) calcitriol ( AUC0 - 72h oral , 1399 + /- 979 pg/mL. hour vs. IV 2793 + /- 1102 pg/mL. hour , P < 0.01 ) , but the mean intestinal Sr absorption was not different [ SrAUC0 - 240min during the 4 hours after Sr administration 2867 + /- 1101 FAD% ( fraction of the absorbed dose ) vs. 3117 + /- 1581 FAD% with oral and IV calcitriol , respectively ] . The calcitriol-stimulated Sr absorption was more then 30 % higher compared with control values ( 2165 + /- 176 FAD% ) . A significant decrease in plasma iPTH was noted 12 hours after the administration of the calcitriol bolus , which was maintained for up to 72 hours without any differences regarding the two routes of administration . CONCLUSIONS These results demonstrate that under acute conditions , intravenous and oral calcitriol boli equally stimulate calcium absorption and had a similar efficacy in suppressing PTH secretion Secondary hyperparathyroidism was suppressed over a period of one year in 12 children with chronic renal failure by using a regimen of mild dietary phosphate restriction and high dose phosphate binders . The patients were r and omised to receive either aluminium hydroxide or calcium carbonate by mouth for six months and then crossed over to the other medication . Vitamin D ( dihydrotachysterol ) dosage was unchanged . Serum parathyroid hormone concentrations were reduced to within the normal range , urinary cyclic adenosine monophosphate values fell , plasma phosphate concentrations decreased , and the theoretical renal phosphate threshold increased significantly . Transiliac bone biopsy findings improved in four patients with adequate suppression of parathyroid hormone concentrations , deteriorated in two patients who were not compliant , and did not change in five patients in whom initial bone disease was mild . Growth velocity improved significantly . There was no difference in the clinical response , biochemical changes , or incidence of complications during treatment with the two agents . In view of the risk of aluminium toxicity the use of high dose calcium carbonate with dietary phosphate restriction and vitamin D supplementation is recommended in the control of secondary hyperparathyroidism in children with chronic renal failure T he renal bone diseases represent a spectrum of skeletal disorders ranging from the high-turnover lesions of secondary hyperparathyroidism to the lowturnover lesions of osteomalacia and adynamic bone . Secondary hyperparathyroidism is the most common skeletal lesion in pediatric patients undergoing regular dialysis ; in contrast , the adynamic lesion of renal osteodystrophy without aluminum has become pre dominant in adult patients treated with continuous ambulatory peritoneal dialysis ( CAPD ) ( 1 - 3 ) . Peritoneal dialysis , on the other h and , is the most common dialytic modality for children with end-stage renal disease , and persistent bone disease remains a major challenge in the clinical management of these patients . Treatment with daily doses of calcitriol or with 1,25dihydroxyvitamin D has been recommended for pediatric patients with chronic renal failure to improve linear growth and to prevent bone deformities . However , secondary hyperparathyroidism persists in a substantial proportion of patients treated with daily calcitriol therapy and receiving peritoneal dialysis ( 1,4 ) . More recently , large intermittent doses of calcitriol given two or three times per week have been used to treat secondary hyperparathyroidism in both children and adults ( 5 - 7 ) . Most studies have employed the oral or intravenous routes of calcitriol adminis tration , but there is little available information about the effect of intraperitoneal ( IP ) doses of calcitriol on bone and mineral metabolism in patients undergoing regular peritoneal dialysis . We have recently completed a prospect i ve r and omized clinical trial to evaluate the biochemical and his tological responses to intermittent calcitriol therapy using thrice weekly IP or oral ( PO ) doses in Background There are no robust guidelines on strategies to prevent the adverse skeletal effects of glucocorticoids in children . Objectives To evaluate the role of prophylactic calcium and vitamin D on bone health in children with new-onset nephrotic syndrome ( NS ) treated with short-term ( 12 weeks ) , high-dose glucocorticoids . Methods Prospect i ve , r and omized , controlled , single blind , interventional study conducted on 41 steroid-naïve pre-pubertal children ( 29 boys , 12 girls ) . All children received prednisolone for 12 weeks ( 60 mg/m2/day daily for 6 weeks , followed by 40 mg/m2/day alternate days for 6 weeks ) . Recruited children were r and omized into the intervention group ( IG ; vitamin D 1,000 IU/day and elemental calcium 500 mg/day ) and the control group ( CG ) . Bone mineral content ( BMC ) and bone mineral density ( BMD ) at the lumbar spine ( L1–L4 ) were estimated at baseline and at 12 weeks . Mean percentage changes in BMC and BMD in IG and CG were compared . Results Children in the IG showed an increase of 11.2 % in BMC versus the CG , who showed an 8.9 % fall ( p < 0.0001 ) . Net intervention-attributable difference in BMC was 20.1 % . BMD increased in both groups ( IG 2.8 % vs CG 0.74 % ) , but the difference was not statistically significant ( p = 0.27 ) . Conclusions Short-term , high-dose glucocorticoid therapy decreases the BMC of the lumbar spine in steroid-naïve children with NS . Vitamin D and calcium co-administration not only prevents this decline , but also enhances BMC of the lumbar spine Background The relative effectiveness and safety of sevelamer , a mineral-free phosphate binder , for treatment of hyperphosphatemia in children with chronic kidney disease is uncertain . Aim This study was design ed to compare the efficacy and acceptability of sevelamer hydrochloride to calcium acetate as a phosphate binder in pediatric patients with chronic kidney disease . Methods A 12-week open-label trial of sevelamer hydrochloride vs calcium acetate was initiated in 22 patients , aged 2–18 , with CKD stages 3 and 4 . After a 2-week washout of phosphate binders and vitamin D , patients were r and omized to receive sevelamer hydrochloride or calcium acetate . The effect of therapy was adjusted for baseline blood levels of calcium , phosphorus , calcium-phosphate product , alkaline phosphatase , PTH and GFR using ANOVA . The primary end point was the decrease in serum phosphorus levels after 12 weeks of treatment . Results Of the 22 patients enrolled , data of 19 patients were used for analysis . The adjusted mean serum phosphate levels at 12 weeks did not differ significantly between calcium acetate- ( 5.3 mg/dl ) and sevelamer-treated subjects ( 6.1 mg/dl ) ( P adjusted means = 0.6 ) . The adjusted blood level of calcium at 12 weeks was significantly lower in the sevelamer-treated patients ( 8.2 mg/dl ) compared to those treated with calcium acetate ( 9.1 mg/dl ) ( P adjusted means = 0.01 ) . In the sevelamer group , there was a non-significant decrease in serum bicarbonate , whereas the total and LDL cholesterol significantly decreased at 12 weeks ( P = 0.04 ) . Sevelamer hydrochloride was well tolerated and without adverse effects related to the drug . Conclusions Compared to calcium acetate , use of sevelamer in children with chronic kidney disease is associated with similar reduction in serum phosphate levels , lower risk of hypercalcemia , Output:

Bone disease , assessed by changes in PTH levels , is improved by all vitamin D preparations . However , no consistent differences between routes of administration , frequencies of dosing or vitamin D preparations were demonstrated . Although fewer episodes of high calcium levels occurred with the non-calcium-containing phosphate binder , sevelamer , compared with calcium-containing binders , there were no differences in serum phosphorus and calcium overall and phosphorus values were reduced to similar extents . All studies were small with few data available on patient-centred outcomes ( growth , bone deformities ) and limited data on biochemical parameters or bone histology result ing in considerable imprecision of results thus limiting the applicability to the care of children with CKD

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***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 aim of the SPHERE study is to design , implement and evaluate tailored practice and personal care plans to improve the process of care and objective clinical outcomes for patients with established coronary heart disease ( CHD ) in general practice across two different health systems on the isl and of Irel and .CHD is a common cause of death and a significant cause of morbidity in Irel and . Secondary prevention has been recommended as a key strategy for reducing levels of CHD mortality and general practice has been highlighted as an ideal setting for secondary prevention initiatives . Current indications suggest that there is considerable room for improvement in the provision of secondary prevention for patients with established heart disease on the isl and of Irel and . The review literature recommends structured programmes with continued support and follow-up of patients ; the provision of training , tailored to practice needs of access to evidence of effectiveness of secondary prevention ; structured recall programmes that also take account of individual practice needs ; and patient-centred consultations accompanied by attention to disease management guidelines . Methods SPHERE is a cluster r and omised controlled trial , with practice -level r and omisation to intervention and control groups , recruiting 960 patients from 48 practice s in three study centres ( Belfast , Dublin and Galway ) . Primary outcomes are blood pressure , total cholesterol , physical and mental health status ( SF-12 ) and hospital re-admissions . The intervention takes place over two years and data is collected at baseline , one-year and two-year follow-up . Data is obtained from medical charts , consultations with practitioners , and patient postal question naires . The SPHERE intervention involves the implementation of a structured systematic programme of care for patients with CHD attending general practice . It is a multi-faceted intervention that has been developed to respond to barriers and solutions to optimal secondary prevention identified in preliminary qualitative research with practitioners and patients . General practitioners and practice nurses attend training sessions in facilitating behaviour change and medication prescribing guidelines for secondary prevention of CHD . Patients are invited to attend regular four-monthly consultations over two years , during which targets and goals for secondary prevention are set and review ed . The analysis will be strengthened by economic , policy and qualitative components BACKGROUND The decreased use of electronic fetal monitoring ( EFM ) for healthy women in labour and the increased provision of professional support to all women in labour is recommended by experts . We evaluated the effectiveness of a community-wide approach to transferring research results to practice using a regional committee , newsletter articles and annual conference presentations compared with an additional tailored hospital intervention involving workshops to enhance self-efficacy for nurses , policy review , multidisciplinary meetings , rounds and unit discussion s. METHODS We compared the proportion of women at low risk who received EFM and the proportion of nurses ' time spent providing labour support before and after the intervention within each of 4 hospitals ( 2 tertiary and 2 secondary ) . One hospital of either type was r and omly selected to receive the tailored intervention . R and omly selected charts ( n = 200 ) were review ed for the use of EFM at each hospital before ( 1995 ) and after ( 1996 ) the intervention . Trained observers at r and omly selected times recorded the nurses ' activities , including time spent providing labour support before and after the intervention . RESULTS At the intervention secondary hospital , there was a large decrease in the use of EFM , from 90.1 % before to 41.0 % after the intervention ( p < 0.001 ) , but no change in nurses ' time spent providing labour support . At the intervention tertiary hospital there was no change in EFM rates , but there was a small , statistically significant increase in time spent providing labour support ( 23.5 % to 29.8 % , p < 0.001 ) . A negative effect on time spent providing labour support was found at the control secondary hospital ( decrease from 19.6 % to 12.8 % , p < 0.001 ) , with no change in the EFM rate . At the control tertiary hospital there was a small decrease in the use of EFM , from 99.5 % to 91.4 % ( p < 0.001 ) , but no change in time spent providing labour support . INTERPRETATION The results are mixed , and the tailored intervention thus appeared to have limited effects . No association was found between the reduction in the use of EFM and an increase in nurses ' time spent providing labour support Background Apart from direct protection and reduced productivity loss during epidemics , the main reason to immunize healthcare workers ( HCWs ) against influenza is to provide indirect protection of frail patients through reduced transmission in healthcare setting s. Because the vaccine uptake among HCWs remains far below the health objectives , systematic programs are needed to take full advantage of such vaccination . In an earlier report , we showed a mean 9 % increase of vaccine uptake among HCWs in nursing homes that implemented a systematic program compared with control homes , with higher rates in those homes that implemented more program elements . Here , we report in detail the process of the development of the implementation program to enable research ers and practitioners to develop intervention programs tailored to their setting . Methods We applied the intervention mapping ( IM ) method to develop a theory- and evidence -based intervention program to change vaccination behaviour among HCWs in nursing homes . Results After a comprehensive needs assessment , we were able to specify proximal program objectives and selected methods and strategies for inducing behavioural change . By consensus , we decided on planning of three main program components , i.e. , an outreach visit to all nursing homes , plenary information meetings , and the appointment of a program coordinator -- preferably a physician -- in each home . Finally , we planned program adoption , implementation , and evaluation . Conclusion The IM methodology result ed in a systematic , comprehensive , and transparent procedure of program development . A potentially effective intervention program to change influenza vaccination behaviour among HCWs was developed , and its impact was assessed in a clustered r and omised controlled trial UNLABELLED INTRODUCTION AND OBJECTIVES . Clinical practice in unstable angina is not always based on best evidence . Guidelines have the potential to improve quality of health care . There are no r and omised trials assessing implementation strategies in the public healthcare system of Spain yet . OBJECTIVE to compare the effectiveness of a multifaceted strategy ( interactive educational meetings , local consensus process ) for guideline implementation in unstable angina , with a passive dissemination strategy . Patients and method . SETTING 10 wards from 3 university hospitals in Sevilla . PARTICIPANTS 153 specialists ( cardiologists , internists ) and their patients admitted for an unstable angina episode . DESIGN a pragmatic , before and after cluster r and omized controlled trial . Intervention was delivered from January to April 1998 . Retrospective data collection took place in July 1999 , of those pre and post-intervention episodes attended from January to October 1997 and from September 1998 to June 1999 , respectively . OUTCOMES compliance with the guideline recommendations for coronary angiography and stress testing , and ejection fraction assessment . RESULTS The multifaceted strategy compared with the passive one , was associated with an absolute improvement in the appropriateness of use of coronary angiography and stress testing of 11 % ( 95 % CI , 0.85 - 21.1 ) , P=.03 . There was no association for the assessment of the ejection fraction : absolute improvement of 1.1 % ( 95 % CI , --15.9 to 18.1 ) , P=.88 . CONCLUSIONS Our results show that a combination of interactive educational meetings and local consensus process delivered to wards of physicians may improve the appropriateness of use of coronary angiography and stress testing Abstract Objective : To compare the effect of individual educational visits versus group visits using academic detailing to discuss prescribing of highly anticholinergic antidepressants in elderly people . Design : R and omised controlled trial with three arms ( individual visits , group visits , and a control arm ) . Setting : Southwest Netherl and s. Participants : 190 general practitioners and 37 pharmacists organised in 21 peer review groups were studied using a data base covering all prescriptions to people covered by national health insurance in the area ( about 240 000 ) . Intervention : All general practitioners and pharmacists in both intervention arms were offered two educational visits . For physicians in groups r and omised to the individual visit arm , 43 of 70 general practitioners participated ; in the group visit intervention arm , five of seven groups ( 41 of 52 general practitioners ) participated . Main outcome measures : Numbers of elderly people ( 60 years ) with new prescriptions of highly anticholinergic antidepressants and less anticholinergic antidepressants . Results : An intention to treat analysis found a 26 % reduction in the rate of starting highly anticholinergic antidepressants in elderly people ( 95 % confidence interval —4 % to 48 % ) in the individual intervention arm and 45 % ( 8 % to 67 % ) in the group intervention arm . The use of less anticholinergic antidepressants increased by 40 % ( 6 % to 83 % ) in the individual intervention arm and 29 % ( —7 % to 79 % ) in the group intervention arm . Conclusions : Both the individual and the group visits decreased the use of highly anticholinergic antidepressants and increased the use of less anticholinergic antidepressant in elderly people . These approaches are practical means to improve prescribing by continuing medical education Astract Background Evidence implementation continues to challenge health professionals most especially those from developing countries . Filipino physiotherapists represent a group of health professionals in a developing country who by tradition and historical practice , take direction from a doctor , on treatment options . Lack of autonomy in decision-making challenges their capacity to deliver evidence -based care . However , this scenario should not limit them from updating and up-skilling themselves on evidence - based practice ( EBP ) . EBP training tailored to their needs and practice was developed to address this gap . This study will be conducted to assess the effectiveness of a tailored EBP-training program for Filipino physiotherapists , in improving knowledge , skills , attitudes and behaviour to EBP . Participation in this program aims to improve capacity to EBP and engage with referring doctors to determine the most effective treatments for their patients . Methods / Design A double blind r and omised controlled trial , assessing the effectiveness of the EBP training intervention , compared with a waitlist control , will be conducted . An adequately powered sample of 54 physiotherapists from the Philippines will be recruited and r and omly allocated to EBP intervention or waitlist control . Intervention : The EBP program for Filipino physiotherapists is a one-day program on EBP principles and techniques , delivered using effective adult education strategies . It consists of lectures and practical workshops . A novel component in this program is the specially-developed recommendation form , which participants can use after completing their training , to assist them to negotiate with referring doctors regarding evidence -based treatment choices for their patients .Pre and post measures of EBP knowledge , skills and attitudes will be assessed in both groups using the Adapted Fresno Test and the Questions to EBP attitudes . Behaviour to EBP will be measured using activity diaries for a period of three months . Discussion Should the EBP-training program be found to be effective in improving EBP-uptake in Filipino physiotherapists , it will form the basis of a much needed national intervention which is context ually appropriate to Filipino physiotherapists . It will therefore form the genesis for a model for building EBP capacity of other health professionals in the Philippines as well as physiotherapists in developing countries . Trial Registration Current Controlled Trials : IS RCT BACKGROUND The number of people residing in nursing homes has increased . General practitioners ( GPs ) receive an increased capitation fee for elderly patients in recognition of their higher consultation rate . However , there is no distinction between elderly patients residing in nursing homes and those in the community . AIM To determine whether nursing home residents receive greater general practice input than people residing in the community . METHOD Prospect i ve comparative study of all 345 residents of eight nursing homes in Glasgow and a 2:1 age , sex , and GP matched comparison group residing in the community . A comparison of contacts with primary care over three months in terms of frequency , nature , length , and outcome was carried out . RESULTS Nursing home residents received more total contacts with primary care staff ( P < 0.0001 ) and more face-to-face consultations with GPs ( P < 0.0001 ) . They were more likely to be seen as an emergency ( P < 0.01 ) but were no more likely to be referred to hospital , and were less likely to be followed-up by their GP ( P < 0.0001 ) . Although individual consultations with nursing home residents were shorter than those with the community group ( P < 0.0001 ) , the overall time spent consulting with them was longer ( P < 0.001 ) . This equated to an additional 28 minutes of time per patient per annum . Some of this time would have been offset by less time spent travelling , since 61 % of nursing home consultations were done during the same visit as other consultations , compared with only 3 % of community consultations ( P < 0.0001 ) . CONCLUSION Our study suggests that nursing home residents do require a greater input from general practice than people of the same age and sex who are residing in the community . While consideration may be given to greater financial reimbursement of GPs who provide medical care to nursing home residents , consideration should also be given to restructuring the medical cover for nursing home residents . This would result in a greater scope for proactive and preventive interventions and for consulting with several patients during one visit BACKGROUND We assessed patient outcomes 90 days after hospital admission for stroke following a multidisciplinary intervention targeting evidence -based management of fever , hyperglycaemia , and swallowing dysfunction in acute stroke units ( ASUs ) . METHODS In the Quality in Acute St Output:

Despite the increase in the number of new studies identified , our overall finding is similar to that of the previous review . Tailored implementation can be effective , but the effect is variable and tends to be small to moderate . It is not yet clear how best to tailor interventions and therefore not clear what the effect of an optimally tailored intervention would be

MS214170

***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 many observational studies , a higher intake of individual antioxidants is inversely associated with lung cancer risk . Data from in vitro and animal experiments suggest that there are biochemical interactions among antioxidant nutrients ; therefore , consideration of multiple antioxidants simultaneously may be important in terms of risk estimation . The authors constructed a dietary antioxidant index and evaluated its ability to predict lung cancer risk within the Alpha-Tocopherol , Beta-Carotene Cancer Prevention Study cohort . At baseline ( 1985 - 1988 ) , 27,111 Finnish male smokers aged 50 - 69 years completed a dietary question naire that assessed usual frequency of consumption and portion sizes for the previous 12 months . A total of 1,787 incident cases of lung cancer were identified during a follow-up period of up to 14.4 years ( 1985 - 1999 ) . Principal components analyses were individually applied to the carotenoid , flavonoid , and vitamin E nutrient groups , and summation of retained principal component scores , plus selenium and vitamin C , yielded the composite antioxidant index . In multivariate proportional hazards models , the relative risks for lung cancer according to increasing quintiles of the antioxidant index were 1.00 ( referent ) , 1.00 ( 95 % confidence interval ( CI ) : 0.87 , 1.14 ) , 0.91 ( 95 % CI : 0.79 , 1.05 ) , 0.79 ( 95 % CI : 0.68 , 0.92 ) , and 0.84 ( 95 % CI : 0.72 , 0.98 ) ( p for trend = 0.002 ) . These findings support the hypothesis that a combination of dietary antioxidants reduces lung cancer risk in male smokers Oxidative stress may enhance prostatic carcinogenesis . A polymorphism [ valine ( V ) -- > alanine ( A ) ] of manganese superoxide dismutase ( MnSOD ) , the primary antioxidant enzyme in mitochondria , has been recently associated with prostate cancer . We examined the relationship between prostate cancer and the MnSOD polymorphism and its interactions with baseline plasma antioxidant levels ( selenium , lycopene , and alpha-tocopherol ) and beta-carotene treatment among 567 cases and 764 controls nested in the prospect i ve Physicians ' Health Study . We found little overall association between MnSOD polymorphism and prostate cancer risk ; however , this polymorphism significantly modified risk of prostate cancer associated with prediagnostic plasma antioxidants ( P(interaction ) > or = 0.05 ) . Among men with the AA genotype , high selenium level ( 4th versus 1st quartile ) was associated with a relative risk ( RR ) of 0.3 [ 95 % confidence interval ( CI ) , 0.2 - 0.7 ] for total prostate cancer ; for clinical ly aggressive prostate cancer , the RR was 0.2 ( 95 % CI , 0.1 - 0.5 ) . In contrast , among men with the VV/VA genotype , the RRs were 0.6 ( 0.4 - 1.0 ) and 0.7 ( 0.4 - 1.2 ) for total and clinical ly aggressive prostate cancer . These patterns were similar for lycopene and alpha-tocopherol and were particularly strong when these antioxidants and selenium were combined ; men with the AA genotype had a 10-fold gradient in risk for aggressive prostate cancer across quartiles of antioxidant status . Men with AA genotype who were r and omly assigned to beta-carotene treatment ( versus placebo ) had a RR of 0.6 ( 95 % CI , 0.2 - 0.9 ; P(interaction ) = 0.03 ) for fatal prostate cancer , but no significant association was observed in men with the VV/VA genotype . Both endogenous and exogenous antioxidants play an important and interdependent role in preventing clinical ly significant prostate cancer BACKGROUND Multivitamin supplements are used by millions of Americans because of their potential health benefits , but the relationship between multivitamin use and prostate cancer is unclear . METHODS We prospect ively investigated the association between multivitamin use and risk of prostate cancer ( localized , advanced , and fatal ) in 295,344 men enrolled in the National Institutes of Health (NIH)-AARP Diet and Health Study who were cancer free at enrollment in 1995 and 1996 . During 5 years of follow-up , 10,241 participants were diagnosed with incident prostate cancer , including 8765 localized and 1476 advanced cancers . In a separate mortality analysis with 6 years of follow-up , 179 cases of fatal prostate cancer were ascertained . Multivitamin use was assessed at baseline as part of a self-administered , mailed food-frequency question naire . Relative risks ( RRs ) and 95 % confidence intervals ( CIs ) were calculated by use of Cox proportional hazards regression , adjusted for established or suspected prostate cancer risk factors . RESULTS No association was observed between multivitamin use and risk of localized prostate cancer . However , we found an increased risk of advanced and fatal prostate cancers ( RR = 1.32 , 95 % CI = 1.04 to 1.67 and RR = 1.98 , 95 % CI = 1.07 to 3.66 , respectively ) among men reporting excessive use of multivitamins ( more than seven times per week ) when compared with never users . The incidence rates per 100,000 person-years for advanced and fatal prostate cancers for those who took a multivitamin more than seven times per week were 143.8 and 18.9 , respectively , compared with 113.4 and 11.4 in never users . The positive associations with excessive multivitamin use were strongest in men with a family history of prostate cancer or who took individual micronutrient supplements , including selenium , beta-carotene , or zinc . CONCLUSION These results suggest that regular multivitamin use is not associated with the risk of early or localized prostate cancer . The possibility that men taking high levels of multivitamins along with other supplements have increased risk of advanced and fatal prostate cancers is of concern and merits further evaluation 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 BACKGROUND Selenium is a potential chemopreventive agent against prostate cancer , whose chemoprotective effects are possibly mediated through the antioxidative properties of selenoenzymes . Interrelations with other antioxidative agents and oxidative stressors , such as smoking , are poorly understood . OBJECTIVES The aims were to investigate the association between serum selenium and prostate cancer risk and to examine interactions with other antioxidants and tobacco use . DESIGN A nested case-control study was performed within the screening arm of the Prostate , Lung , Colorectal , and Ovarian Cancer Screening Trial . Serum selenium in prospect ively collected sample s was compared between 724 incident prostate cancer case subjects and 879 control subjects , frequency-matched for age , time since initial screen , and year of blood draw . The men were followed for up to 8 y. RESULTS Overall , serum selenium was not associated with prostate cancer risk ( P for trend = 0.70 ) ; however , higher serum selenium was associated with lower risks in men reporting a high ( more than the median : 28.0 IU/d ) vitamin E intake [ odds ratio ( OR ) for the highest compared with the lowest quartile of selenium : 0.58 ; 95 % CI : 0.37 , 0.91 ; P for trend = 0.05 ; P for interaction = 0.01 ] and in multivitamin users ( OR for highest compared with the lowest quartile of selenium : 0.61 ; 95 % CI : 0.36 , 1.04 ; P for trend = 0.06 ; P for interaction = 0.05 ) . Furthermore , among smokers , high serum selenium concentrations were related to reduced prostate cancer risk ( OR for the highest compared with the lowest quartile of selenium : 0.65 ; 95 % CI : 0.44 , 0.97 ; P for trend = 0.09 ; P for interaction = 0.007 ) . CONCLUSION Greater prediagnostic serum selenium concentrations were not associated with prostate cancer risk in this large cohort , although greater concentrations were associated with reduced prostate cancer risks in men who reported a high intake of vitamin E , in multivitamin users , and in smokers The association between prostate cancer and baseline vitamin E and selenium was evaluated in the trial-based cohort of the Alpha-Tocopherol , Beta-Carotene Cancer Prevention Study ( n = 29,133 ) . During up to 9 years of follow-up , 317 men developed incident prostate cancer . Multivariate Cox proportional hazards models that adjusted for intervention group , benign prostatic hyperplasia , age , smoking , and urban residence were used to evaluate associations between prostate cancer and exposures of interest . There were no significant associations between baseline serum alpha-tocopherol , dietary vitamin E , or selenium and prostate cancer overall . The associations between prostate cancer and vitamin E and some of the baseline dietary tocopherols differed significantly by alpha-tocopherol intervention status , with the suggestion of a protective effect for total vitamin E among those who received the alpha-tocopherol intervention ( relative risk was 1.00 , 0.68 , 0.80 , and 0.52 for increasing quartiles ; P = 0.07 ) 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 Linxian , China has some of the highest rates of esophageal/gastric cardia cancer in the world , and epidemiological evidence suggests that chronically low intake of micronutrients may contribute to these high cancer rates . To examine whether supplementation with multiple vitamins and minerals can affect the occurrence of esophageal/gastric cardia cancer in this population , a two-arm r and omized nutrition intervention trial was conducted among 3318 Linx Output:

RCTs with low risk of bias suggested increased melanoma risk . Results for most outcomes were similar when we included all RCTs in the meta- analysis , regardless of risk of bias . Summary RRs for site-specific cancers showed limited changes compared with estimates from high- quality studies alone , except for liver cancer , for which results were reversed . No clear evidence of an influence of baseline participant selenium status on outcomes has emerged in these studies .Observational longitudinal studies have shown an inverse association between selenium exposure and risk of some cancer types , but null and direct relations have also been reported , and no systematic pattern suggesting dose-response relations has emerged . Overall , there is no evidence to suggest that increasing selenium intake through diet or supplementation prevents cancer in humans .

MS214171

***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 Therapeutic decisions in atrial fibrillation ( AF ) are often influenced by assessment of bleeding risk . However , existing bleeding risk scores have limitations . Objectives We sought to develop and vali date a novel bleeding risk score using routinely available clinical information to predict major bleeding in a large , community-based AF population . Methods We analysed data from Outcomes Registry for Better Informed Treatment of Atrial Fibrillation ( ORBIT-AF ) , a prospect i ve registry that enrolled incident and prevalent AF patients at 176 US sites . Using Cox proportional hazards regression , we identified factors independently associated with major bleeding among patients taking oral anticoagulation ( OAC ) over a median follow-up of 2 years ( interquartile range = 1.6–2.5 ) . We also created a numerical bedside risk score that included the five most predictive risk factors weighted according to their strength of association with major bleeding . The predictive performance of the full model , the simple five-item score , and two existing risk scores ( hypertension , abnormal renal/liver function , stroke , bleeding history or predisposition , labile INR , elderly , drugs/alcohol concomitantly , HAS-BLED , and anticoagulation and risk factors in atrial fibrillation , ATRIA ) were then assessed in both the ORBIT-AF cohort and a separate clinical trial population , Rivaroxaban Once-daily oral direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation ( ROCKET-AF ) . Results Among 7411 ORBIT-AF patients taking OAC , the rate of major bleeding was 4.0/100 person-years . The full continuous model ( 12 variables ) and five-factor ORBIT risk score ( older age [ 75 + years ] , reduced haemoglobin/haematocrit/history of anaemia , bleeding history , insufficient kidney function , and treatment with antiplatelet ) both had good ability to identify those who bled vs. not ( C-index 0.69 and 0.67 , respectively ) . These scores both had similar discrimination , but markedly better calibration when compared with the HAS-BLED and ATRIA scores in an external validation population from the ROCKET-AF trial . Conclusions The five-element ORBIT bleeding risk score had better ability to predict major bleeding in AF patients when compared with HAS-BLED and ATRIA risk scores . The ORBIT risk score can provide a simple , easily remembered tool to support clinical decision making Better underst and ing of risk factors for major bleeding events during anticoagulant treatment for venous thromboembolism ( VTE ) may help physicians when deciding on intensity and duration of treatment . The primary aim of this study was to identify risk factors for major and clinical ly relevant bleeding in patients receiving the oral factor Xa inhibitor edoxaban or warfarin for the treatment of acute VTE . We analysed data from 8240 patients who received ≥1 dose of study drug in the Hokusai-VTE study . Bleeding risk factors were evaluated in 4118 patients who received edoxaban and significant variables were combined in a prediction model . We used the C-statistic to estimate model discrimination and bootstrap techniques for internal validation . Major bleeding occurred in 56/4118 ( 1.4 % ) patients given edoxaban and in 66/4122 ( 1.6 % ) patients given warfarin . Clinical ly relevant bleeding occurred in 349 ( 8.5 % ) and 423 ( 10.3 % ) , respectively . Significant risk factors for major bleeding during edoxaban treatment were female sex , concomitant antiplatelet therapy , haemoglobin ≤10 g/dl , history of arterial hypertension , and systolic blood pressure > 160 mmHg . The discrimination of the model was high ( C-statistic : 0.71 ) for major bleeding , lower for clinical ly relevant bleeding ( C-statistic : 0.62 ) and when the model was applied to patients receiving warfarin ( C-statistic 0.60 ) . In conclusion , we identified five main predictors of major bleeding in patients receiving edoxaban for the treatment of acute VTE . A risk model based on these factors predicted an increased risk of bleeding with good discrimination Attempts at identifying patients with an elevated risk of bleeding while on anticoagulation following acute venous thromboembolism ( VTE ) have largely been unsuccessful thus far . We sought to develop a clinical prediction score for bleeding during stable anticoagulation treatment after acute VTE . We performed a post hoc analysis of the pooled RE-COVER studies , two double-blind r and omised “ sister ” trials evaluating dabigatran versus st and ard treatment in 5107 VTE patients . A score was derived from patients r and omised to dabigatran using logistic regression analysis covering the complete follow-up period . The final model , named VTE-BLEED , included six variables and yielded a c-statistic of 0.72 ( 95 % CI 0.67–0.76 ) . Patients from the derivation cohort in the low-risk group ( < 2 points ; 74 % of the derivation population ) had a bleeding incidence of 2.8 % compared to 12.6 % in the elevated-risk group ( OR 5.0 ; 95 % CI 3.5–7.1 ) . The score proved accurate for our primary end-point , i.e. prediction of major bleeding after day 30 ( “ stable ” anticoagulation ) , both in patients on dabigatran ( c-statistic 0.75 , 95 % CI 0.61–0.89 ) and those on warfarin ( 0.78 , 95 % CI 0.68–0.86 ; p=0.77 for difference ) . The new VTE-BLEED score accurately predicted major bleeding events in VTE patients on stable anticoagulation with both dabigatran and warfarin . The new VTE-BLEED score predicted major bleeding events in VTE patients on stable anticoagulation treatment Existing clinical scores do not perform well in predicting bleeding in elderly patients with acute venous thromboembolism ( VTE ) . We sought to derive an easy-to-use clinical score to help physicians identify elderly patients with VTE who are at high-risk of bleeding during extended anticoagulation ( > 3 months ) . Our derivation sample included 743 patients aged ≥65 years with VTE who were enrolled in a prospect i ve multicenter cohort study . All patients received extended anticoagulation with vitamin K antagonists . We derived our score using competing risk regression , with the time to a first major bleeding up to 36 months of extended anticoagulation as the outcome , and 17 c and i date variables as predictors . We used bootstrapping methods for internal validation . Sixty-six ( 9 % ) patients suffered major bleeding . The clinical score is based on seven clinical factors ( previous bleeding , active cancer , low physical activity , anemia , thrombocytopenia , antiplatelet drugs/NSAIDs , and poor INR control ) . Overall , 48 % of patients were classified as low-risk , 37 % as moderate-risk , and 15 % as high-risk of bleeding . The rate of major bleeding was 1.4 events in low-risk , 5.0 events in moderate-risk , and 12.2 events per 100 patient-years in high-risk patients . The c-statistic was 0.78 at 3 months and 0.71 at 36 months of extended anticoagulation . Model calibration was excellent ( p=0.93 ) . Internal validation showed similar results . This simple clinical score accurately identified elderly patients with VTE who are at high risk of major bleeding and who may not benefit from extended anticoagulation . Further validation of the score is important before its implementation into practice . The study is registered to https:// clinical trials.gov as NCT00973596 PURPOSE To determine the incidence of major bleeding in out patients treated with warfarin and to identify predictive factors known at the start of therapy . PATIENTS AND METHODS The records of 565 patients starting outpatient therapy with warfarin upon discharge from a university hospital were review ed . Follow-up information was obtained for 562 patients ( 99.5 % ) . Bleeding was classified as major or minor using explicit criteria . The cumulative incidence of bleeding was estimated by means of survival analysis . Independent risk factors for major bleeding were identified using Cox regression analysis in 375 r and omly chosen patients ; they were tested in the remaining 187 patients . RESULTS Major bleeding occurred in 65 patients ( 12 % ) and was fatal in 10 patients ( 2 % ) . The cumulative incidences of major bleeding at one , 12 , and 48 months were 3 % , 11 % , and 22 % , respectively . The monthly risk of major bleeding decreased over time , from 3 % during the first month of outpatient therapy to 0.3 % per month after the first year of therapy . Five independent risk factors for major bleeding -- age 65 years or greater , history of stroke , history of gastrointestinal bleeding , a serious comorbid condition ( recent myocardial infa rct ion , renal insufficiency , or severe anemia ) , atrial fibrillation -- predicted major bleeding in the testing group ; the cumulative incidence of major bleeding at 48 months was 2 % in 57 low-risk patients , 17 % in 110 middle-risk patients , and 63 % in 20 high-risk patients . CONCLUSION These findings provide a quantitative basis for evaluating the risk of major bleeding in individual patients at the start of outpatient therapy with warfarin . Whether the risk of bleeding can be reduced in high-risk patients without reducing the benefit of therapy remains to be determined PURPOSE To evaluate the accuracy and clinical utility of the Outpatient Bleeding Risk Index for estimating the probability of major bleeding in out patients treated with warfarin . The index was previously derived in a retrospective cohort of 556 patients from a different hospital ( derivation cohort ) . SUBJECTS AND METHODS We enrolled 264 out patients starting warfarin ( validation cohort ) to vali date the index prospect ively . All patients were identified upon hospital discharge , and physician estimates of the probability of major bleeding were obtained before discharge in the validation cohort . RESULTS Major bleeding occurred in 87 of 820 out patients ( 6.5%/yr ) . The index included four independent risk factors for major bleeding : age 65 years or greater ; history of gastrointestinal bleeding ; history of stroke ; and one or more of four specific comorbid conditions . In the validation cohort , the index predicted major bleeding : the cumulative incidence at 48 months was 3 % in 80 low-risk patients , 12 % in 166 intermediate-risk patients , and 53 % in 18 high-risk patients ( c index , 0.78 ) . The index performed better than physicians , who estimated the probability of major bleeding no better than expected by chance . Of the 18 episodes of major bleeding that occurred in high-risk patients , 17 were potentially preventable . CONCLUSIONS The Outpatient Bleeding Risk Index prospect ively classified patients according to risk of major bleeding and performed better than physicians . Major bleeding may be preventable in many high-risk patients by avoidance of over-anticoagulation and nonsteroidal anti-inflammatory agents BACKGROUND St and ard therapy to prevent recurrent venous thromboembolism includes 3 to 12 months of treatment with full-dose warfarin with a target international normalized ratio ( INR ) between 2.0 and 3.0 . However , for long-term management , no therapeutic agent has shown an acceptable benefit-to-risk ratio . METHODS Patients with idiopathic venous thromboembolism who had received full-dose anticoagulation therapy for a median of 6.5 months were r and omly assigned to placebo or low-intensity warfarin ( target INR , 1.5 to 2.0 ) . Participants were followed for recurrent venous thromboembolism , major hemorrhage , and death . RESULTS The trial was terminated early after 508 patients had undergone r and omization and had been followed for up to 4.3 years ( mean , 2.1 ) . Of 253 patients assigned to placebo , 37 had recurrent venous thromboembolism ( 7.2 per 100 person-years ) , as compared with 14 of 255 patients assigned to low-intensity warfarin ( 2.6 per 100 person-years ) , a risk reduction of 64 percent ( hazard ratio , 0.36 [ 95 percent confidence interval , 0.19 to 0.67 ] ; P<0.001 ) . Risk reductions were similar for all subgroups , including those with and those without inherited thrombophilia . Major hemorrhage occurred in two patients assigned to placebo and five assigned to low-intensity warfarin ( P=0.25 ) . Eight patients in the placebo group and four in the group assigned to low-intensity warfarin died ( P=0.26 ) . Low-intensity warfarin was thus associated with a 48 percent reduction in the composite end point of recurrent venous thromboembolism , major hemorrhage , or death . According to per- protocol and as-treated analyses , the reduction in the risk of recurrent venous thromboembolism was between 76 and 81 percent . CONCLUSIONS Long-term , low-intensity warfarin therapy is a highly effective method of preventing recurrent venous thromboembolism A score that can accurately determine the risk of major bleeding during anticoagulant therapy may help to make decisions on anticoagulant use . Output:

Discussion The planned systematic review and meta- analysis will provide reliable estimates of the risk for major bleeding events during extended anticoagulation .

MS214172

***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 / AIMS A total of 213 patients with compensated cirrhosis , portal hypertension and no varices were included in a trial evaluating beta-blockers in preventing varices . Predictors of the development of hepatocellular carcinoma ( HCC ) , including hepatic venous pressure gradient ( HVPG ) were analyzed . METHODS Baseline laboratory tests , ultrasound and HVPG measurements were performed . Patients were followed prospect ively every three months until development of varices or variceal bleeding or end of the study in 09/02 . The endpoint was HCC development according to st and ard diagnostic criteria . Univariate and multivariate Cox regression models were developed to identify predictors of HCC . RESULTS In a median follow-up of 58 months 26/213 ( 12.2 % ) patients developed HCC . Eight patients were transplanted and 28 patients died without HCC . Twenty-one ( 84 % ) HCC developed in patients with HCV . On multivariate analysis HVPG ( HR 1.18 ; 95%CI 1.08 - 1.29 ) , albumin ( HR 0.34 ; 95%CI 0.14 - 0.83 ) and viral etiology ( HR 4.59 ; 95%CI 1.51 - 13.92 ) were independent predictors of HCC development . ROC curves identified 10 mmHg of HVPG as the best cut-off ; those who had an HVPG above this value had a 6-fold increase in the HCC incidence . CONCLUSIONS Portal hypertension is an independent predictor of HCC development . An HVPG > 10 mmHg is associated with a 6-fold increase of HCC risk Objective Non-selective β-blockers or endoscopic b and ligation ( EBL ) are recommended for primary prophylaxis of variceal bleeding in patients with oesophageal varices . Additional α-adrenergic blockade ( as by carvedilol ) may increase the number of patients with haemodynamic response ( reduction in hepatic venous pressure gradient ( HVPG ) of ≥20 % or to values < 12 mm Hg ) . Design Patients with oesophageal varices undergoing measurement of HVPG before and under propranolol treatment ( 80–160 mg/day ) were included . HVPG responders were kept on propranolol ( PROP group ) , while non-responders were placed on carvedilol ( 6.25–50 mg/day ) . Carvedilol responders continued treatment ( CARV group ) , while non-responders to carvedilol underwent EBL . The primary aim was to assess haemodynamic response rates to carvedilol in propranolol non-responders . Results 36 % ( 37/104 ) of patients showed a HVPG response to propranolol . Among the propranolol non-responders 56 % ( 38/67 ) eventually achieved a haemodynamic response with carvedilol , while 44 % ( 29/67 ) patients were finally treated with EBL . The decrease in HVPG was significantly greater with carvedilol ( median 12.5 mg/day ) than with propranolol ( median 100 mg/day ) : −19±10 % versus −12±11 % ( p<0.001 ) . During a 2 year follow-up bleeding rates for PROP were 11 % versus CARV 5 % versus EBL 25 % ( p=0.0429 ) . Fewer episodes of hepatic decompensation ( PROP 38%/CARV 26 % vs EBL 55 % ; p=0.0789 ) and significantly lower mortality ( PROP 14%/CARV 11 % vs EBL 31 % ; p=0.0455 ) were observed in haemodynamic responders compared to the EBL group . Conclusions Carvedilol leads to a significantly greater decrease in HVPG than propranolol . Using carvedilol for primary prophylaxis a substantial proportion of non-responders to propranolol can achieve a haemodynamic response , which is associated with improved outcome with regard to prevention of variceal bleeding , hepatic decompensation and death UNLABELLED Current therapy for preventing the first variceal bleed includes beta-blocker and variceal b and ligation ( VBL ) . VBL has lower bleeding rates , with no differences in survival , whereas beta-blocker therapy can be limited by side effects . Carvedilol , a non-cardioselective vasodilating beta-blocker , is more effective in reducing portal pressure than propranolol ; however , there have been no clinical studies assessing the efficacy of carvedilol in primary prophylaxis . The goal of this study was to compare carvedilol and VBL for the prevention of the first variceal bleed in a r and omized controlled multicenter trial . One hundred fifty-two cirrhotic patients from five different centers with grade II or larger esophageal varices were r and omized to either carvedilol 12.5 mg once daily or VBL performed every 2 weeks until eradication using a multib and er device . Seventy-seven patients were r and omized to carvedilol and 75 to VBL . Baseline characteristics did not differ between the groups ( alcoholic liver disease , 73 % ; median Child-Pugh score , 8 ; median age , 54 years ; median follow-up , 20 months ) . On intention-to-treat analysis , carvedilol had lower rates of the first variceal bleed ( 10 % versus 23 % ; relative hazard 0.41 ; 95 % confidence interval 0.19 - 0.96 [ P = 0.04 ] ) , with no significant differences in overall mortality ( 35 % versus 37 % , P = 0.71 ) , and bleeding-related mortality ( 3 % versus 1 % , P = 0.26 ) . Six patients in the VBL group bled as a result of b and ing ulcers . Per- protocol analysis revealed no significant differences in the outcomes . CONCLUSION Carvedilol is effective in preventing the first variceal bleed . Carvedilol is an option for primary prophylaxis in patients with high-risk esophageal varices BACKGROUND AND AIMS Newer studies suggest that carvedilol , a beta-blocker with a moderate anti-alpha-1 activity , is superior to propranolol in reducing the portal pressure and risk of variceal bleeding . The effect on arterial blood pressure is a matter of concern especially in decompensated patients . AIMS to assess potential differential effects of beta-blockers and beta-blockers with moderate anti-alpha-1 activity on selected haemodynamic , humoral , and respiratory characteristics in cirrhosis . METHODS Patients with cirrhosis and portal hypertension were r and omised to receive carvedilol ( n=16 ) or propranolol ( n=13 ) . Cardiac , systemic and splanchnic parameters along with oxygen saturation and plasma renin were measured at inclusion and after 3 months . RESULTS Arterial blood pressure , heart rate , and cardiac output decreased equally , central circulation time and systemic vascular resistance increased significantly but similarly . Central blood volume , plasma volume and arterial compliance were unaltered . The QTc interval and renin levels decreased in the carvedilol group , however not significantly different from the propranolol group . Arterial oxygen saturation and alveolar arterial oxygen gradient remained constant in both groups . Hepatic venous pressure gradient decreased equally in the carvedilol and propranolol groups ( -17 % and -20 % , non significant ) . CONCLUSIONS Systemic haemodynamics and pulmonary effects of carvedilol and propranolol are modest and this study could not demonstrate any significant difference between the two treatments OBJECTIVE : Propranolol is known to decrease portal pressure in cirrhotic patients with portal hypertension ; however , a substantial number of patients do not respond to propranolol administration . The addition of isosorbide-5-mononitrate may enhance portal pressure reduction in patients receiving propranolol . Carvedilol is a nonselective β-blocker with α1-adrenergic blocking activity . It has been shown to decrease portal pressure in cirrhotic patients . Additionally , carvedilol has a greater portal hypotensive effect than propranolol alone in patients with cirrhosis . The current study is aim ed at comparing the acute hemodynamic effects of carvedilol with the effects of propranolol plus isosorbide-5-mononitrate in patients with viral cirrhosis . METHODS : Patients with viral cirrhosis were r and omly assigned to receive an oral administration of carvedilol of 25 mg ( n = 11 ) or an oral administration of propranolol 40 mg plus isosorbide-5-mononitrate 20 mg ( n = 11 ) . Hemodynamic values were measured at basal and 90 min after drugs administration . RESULTS : Both carvedilol and propranolol plus isosorbide-5-mononitrate significantly decreased cardiac index , heart rate , and HVPG . The magnitude of changes in HVPG observed between the basal and after drugs administration was greater in patients receiving carvedilol than in those receiving propranolol plus isosorbide-5-mononitrate ( −18.6 ± 3.6 % vs−10.1 ± 3.6 % , p < 0.05 ) . Hepatic blood flow increased following carvedilol administration but remained unchanged in patients receiving propranolol plus isosorbide-5-mononitrate . The magnitude of decrease in mean arterial pressure ( MAP ) did not differ between the two groups of patients . CONCLUSION : In our patients with viral cirrhosis , carvedilol is more effective than propranolol plus isosorbide-5-mononitrate in the reduction of HVPG . Carvedilol administration causes an increase in hepatic blood flow , but its systemic effects were similar to those of propranolol plus isosorbide-5-mononitrate BACKGROUND Carvedilol , a non-selective beta- and alpha-1 blocking agent , has portal hypotensive action . This study evaluates the acute and 7-day response to carvedilol , and compares it to that of propranolol . METHODS Thirty-six cirrhotics were r and omized into two groups of 18 each , and treated with carvedilol or propranolol . Hepatic venous pressure gradient ( HVPG ) was measured before and 90 min after either 25 mg carvedilol or 80 mg propranolol was administered orally , and again 7 days after 12.5 mg carvedilol daily or 80 mg propranolol daily , respectively . ' Responders ' were defined as those with HVPG reduction of > or = 20 % . RESULTS With carvedilol , 11/18(61.1 % ) and 11/17(64.7 % ) patients responded acutely and after 7 days , respectively , while 9/18(50 % ) and 10/16(62.5 % ) did so to propranolol . However , HVPG reduction ( percent ) by carvedilol was not superior to that by propranolol either acutely ( 27.67 + /- 31.49 compared to 22.98 + /- 27.40 , P = 0.6 ) or after 7 days ( 28.2 + /- 29.05 compared to 23.25 + /- 20.15 , P = 0.6 ) . With carvedilol , the acute HVPG response ( P < 0.001 ) and responder status ( P = 0.018 ) were good predictors of the response after 7 days , but were weak predictors in the case of propranolol ( 0.1 > P > 0.05 and P = 0.059 , respectively ) . On carvedilol , only one patient ( with ascites ) developed symptomatic systemic hypotension with oliguria . CONCLUSION Carvedilol is a relatively safe , effective portal hypotensive agent , both acutely and over 7 days , but not superior to propranolol , at least in Indians . The acute hemodynamic response seems promising in predicting long-term response BACKGROUND AND AIMS Our aim was to identify predictors of clinical decompensation ( defined as the development of ascites , variceal hemorrhage [ VH ] , or hepatic encephalopathy [ HE ] ) in patients with compensated cirrhosis and with portal hypertension as determined by the hepatic venous pressure gradient ( HVPG ) . METHODS We analyzed 213 patients with compensated cirrhosis and portal hypertension but without varices included in a trial evaluating the use of beta-blockers in preventing varices . All had baseline laboratory tests and HVPG . Patients were followed prospect ively every 3 months until development of varices or VH or end of study . To have complete information , until study termination , about clinical decompensation , medical record review was done . Patients who underwent liver transplantation without decompensation were censored at transplantation . Cox regression models were developed to identify predictors of clinical decompensation . Receiver operating characteristic ( ROC ) curves were constructed to evaluate diagnostic capacity of HVPG . RESULTS Median follow-up time of 51.1 months . Sixty-two ( 29 % ) of 213 patients developed decompensation : 46 ( 21.6 % ) ascites , 6 ( 3 % ) VH , 17 ( 8 % Output:

Adverse events were nonsignificantly more frequent and serious with carvedilol . CONCLUSIONS Carvedilol reduces portal hypertension significantly more than propranolol . However , available data do not allow a satisfactory comparison of adverse events .

MS214173

***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 Little research has explored pre-transplantation psychological factors as predictors of outcome after liver or kidney transplantation . Our objective is to determine whether report of depressive symptoms on waiting list predicts outcome of liver and kidney transplantation . Methods Patients on waiting list for liver or kidney transplantation were classified for report or non-report of depressive symptoms on waiting list . 339 were transplanted 6 months later on average , and followed prospect ively . The main outcome measures were graft failure and mortality 18 months post-transplantation . Results Among the 339 patients , 51.6 % reported depressive symptoms on waiting list , 16.5 % had a graft failure and 7.4 % died post-transplantation . Report of depressive symptoms on waiting list predicted a 3 to 4-fold decreased risk of graft failure and mortality 18-months post-transplantation , independently from age , gender , current cigarette smoking , anxiety symptoms , main primary diagnosis , UNOS score , number of comorbid diagnoses and history of transplantation . Data were consistent for liver and kidney transplantations . Other baseline predictive factors were : for graft failure , the main primary diagnosis and a shorter length since this diagnosis , and for mortality , older age , male gender and the main primary diagnosis . Conclusion Further studies are needed to underst and the underlying mechanisms of the association between report of depressive symptoms on waiting list and decreased risk of graft failure and mortality after transplantation Background Little is known how health related quality of life ( HRQOL ) change in the transition from dialysis to renal transplantation ( RTX ) . Longitudinal data addressing the patient-related outcomes are scarce , and particularly data regarding kidney-specific HRQOL are lacking . Thus , the aim of the current study was to assess HRQOL in patients followed from dialysis to RTX . Furthermore , to compare HRQOL in RTX patients and the general population . Methods In a prospect i ve study , HRQOL was measured in a cohort of 110 patients ( median age 53.5 ( IQR 39–62 ) years , GFR 54 ( 45–72 ) ml/min/1.73 m2 ) in dialysis and after RTX using the self-administered Kidney Disease and Quality of Life Short Form version 1.3 ( KDQOL-SF ) . Generic HRQOL in the RTX patients was compared to that of the general population ( n = 5903 ) using the SF-36 . Clinical important change after RTX was defined as difference in HRQOL of SD/2 . Results Follow-up time was 55 ( IQR 50–59 ) months , and time after RTX was 41 ( 34–51 ) months . Four of nine domains in kidney-specific HRQOL improved after RTX , i.e. burden of kidney disease , effect of kidney disease , symptoms and work status . In SF-36 , general health , vitality , social function and role physical improved after RTX , but none of the domains improved sufficiently to be regarded as clinical ly relevant change . There were highly significant differences in HRQOL between RTX patients and the general population after adjustment for age and gender for all items of SF-36 except for bodily pain and mental health . Conclusions HRQOL improved in the transition from dialysis to transplantation , but clinical relevant change was only obtained in the kidney specific domains . HRQOL was perceived considerably poorer in RTX patients than in the general population . Our observations point to the need of improving HRQOL even after RTX , and should encourage further longitudinal research and clinical attention during treatment shift Background The high frequency of outpatient visits after kidney transplantation is burdensome to both the recovering patient and health care capacity . Self-monitoring kidney function offers a promising strategy to reduce the number of these outpatient visits . Objective The objective of this study was to investigate whether it is safe to rely on patients ’ self- measurements of creatinine and blood pressure , using data from a self-management r and omized controlled trial . Methods For self-monitoring creatinine , each participant received a StatSensor Xpress-i Creatinine Meter and related test material . For self-monitoring blood pressure , each participant received a Microlife WatchBP Home , an oscillometric device for blood pressure self-measurement on the upper arm . Both devices had a memory function and the option to download stored values to a computer . During the first year post transplantation , 54 patients registered their self-measured creatinine values in a Web-based Self-Management Support System ( SMSS ) which provided automatic feedback on the registered values ( eg , seek contact with hospital ) . Values registered in the SMSS were compared with those logged automatically in the creatinine device to study reliability of registered data . Adherence to measurement frequency was determined by comparing the number of requested with the number of performed measurements . To study adherence to provided feedback , SMSS-logged feedback and information from the electronic hospital files were analyzed . Results Level of adherence was highest during months 2 - 4 post transplantation with over 90 % ( 42/47 ) of patients performing at least 75 % of the requested measurements . Overall , 87.00 % ( 3448/3963 ) of all registered creatinine values were entered correctly , although values were often registered several days later . If ( the number of ) measured and registered values deviated , the mean of registered creatinine values was significantly lower than what was measured , suggesting active selection of lower creatinine values . Adherence to SMSS feedback ranged from 53 % ( 14/24 ) to 85 % ( 33/39 ) , depending on the specific feedback . Conclusions Patients ’ tendency to postpone registration and to select lower creatinine values for registration and the suboptimal adherence to the feedback provided by the SMSS might challenge safety . This should be well considered when design ing self-monitoring care systems , for example by ensuring that self-measured data are transferred automatically to an SMSS ABSTRACT We assessed salivary melatonin levels in renal transplant ( RTx ) recipients who participated in a r and omised , multicentre wait-list controlled trial on the effect of bright light therapy on their sleep and circadian rhythms . A large proportion of RTx recipients in our cohort had unexpectedly low melatonin values , which precluded calculation of the dim-light melatonin onset ( DLMO ) as a circadian marker . Thus , the aim of this post hoc analysis was to describe the melatonin profile of home-dwelling RTx recipients diagnosed with sleep – wake disturbances ( SWDs ) . The participants were characterised by means of sleep question naires , vali date d psychometric instruments [ Pittsburgh sleep quality Index ( PSQI ) , Epworth sleepiness scale ( ESS ) , Morningness-Eveningness Question naire ( MEQ ) and Depression , Anxiety and Stress Scale ( DASS ) ] in addition to melatonin assay in saliva . Data were analysed with descriptive statistics and group comparisons made with appropriate post hoc tests . RTx recipients [ n = 29 ( aged 54.83 ± 13.73 , transplanted 10.62 ± 6.84 years ago ) ] were retrospectively grouped into two groups : RTx recipients whose dim light melatonin onset ( DLMO ) could be calculated ( n = 11 ) and those whose DLMO could not be calculated ( n = 18 ) . RTx recipients having a measurable DLMO had a number of differences from those without DLMO : they were younger [ 46.4 ± 14.9 compared to 60.0 ± 10.3 ( p = .007 ) ] , had higher haemoglobin values [ 135.36 ± 12.01 versus 122.82 ± 11.56 ( p = .01 ) ] , less anxiety [ 4 ( 0;8 ) versus 12 ( 6.5;14 ) ( p = .021 ) ] and a better overall sense of coherence [ SOC Score : 71.09 ± 12.78 versus 56.28 ± 15.48 ( p = 0.013 ) ] . These results suggest that RTx recipients whose DLMO could be calculated have less health impairments , underlying the relevance of a stable circadian system This study assessed the effect and feasibility of morning bright light therapy ( BLT ) on sleep , circadian rhythms , subjective feelings , depressive symptomatology and cognition in renal transplant recipients ( RTx ) diagnosed with sleep-wake disturbances ( SWD ) . This pilot r and omized multicentre wait-list controlled trial included 30 home-dwelling RTx r and omly assigned 1:1 to either 3 weeks of BLT or a wait-list control group . Morning BLT ( 10 000 lux ) was individually scheduled for 30 min daily for 3 weeks . Wrist actimetry ( measuring sleep and circadian rhythms ) , vali date d instruments ( subjective feelings and cognition ) and melatonin assay ( circadian timing ) were used . Data were analysed via a r and om-intercept regression model . Of 30 RTx recipients ( aged 58 ± 15 , transplanted 15 ± 6 years ago ) , 26 completed the study . While BLT had no significant effect on circadian and sleep measures , sleep timing improved significantly . The intervention group showed a significant get-up time phase advance from baseline to intervention ( + 24 min ) [ ( st and ardized estimates ( SE ) : -0.23 ( -0.42 ; -0.03 ) ] and a small ( + 14 min ) but significant bedtime phase advance from intervention to follow-up ( SE : -0.25 ( -0.41 ; -0.09 ) . Improvement in subjective feelings and depressive symptomatology was observed but was not statistically significant . Bright light therapy showed preliminary indications of a beneficial effect in RTx with sleep-wake disturbances . ( Clinical Trials.gov number : NCT01256983 ) End-stage renal disease ( ESRD ) is a serious public health problem . The study of the impact of renal replacement therapy ( RRT ) in quality of life ( QoL ) has become increasingly important . The aim of this study was to evaluate the QoL of patients on RRT and associated factors . 3036 patients on RRT in Brazil were interviewed in relation to socioeconomic , demographic , clinical and QoL aspects . Patients were r and omly selected after a cluster sampling process on two levels : health services and patients . QoL was measured by Eq5D . The instrument allows the indirect measurement of QoL and utility calculation , in addition to the direct measurement of QoL by a visual analog scale ( VAS ) . It was observed that transplant patients have better QoL and that the most prejudicial aspects are pain/discomfort and anxiety/depression . The main factors associated with QOL are age , female gender , variables associated with the clinical condition of the patient such as the need for hospitalization and the presence of comorbidities , social class and variables associated with the health service use . The correlation between VAS and utility calculated was moderate and the 5 Eq5D questions explain 43 % of the variability of VAS . The calculated utility can be used in cost-utility analysis Non‐adherence with immunosuppressive regimen is a major risk factor for poor outcome after kidney transplantation . Identifying patients at risk for non‐adherence requires underst and ing the risk factors for non‐adherence . This prospect i ve study included a convenience sample of 249 adult kidney transplant patients > 1 year post‐transplant . Non‐adherence was monitored electronically using MEMS ® . Selected socio‐economic , therapy‐ , patient‐ , condition‐ and healthcare team‐related risk factors for non‐adherence were assessed . Period prevalences were expressed as the percent of prescribed doses taken ( taking adherence ) , the percent of correctly dosed days ( dosing adherence ) , the percentage of inter‐dose intervals not exceeding 25 % of the prescribed interval ( timing adherence ) , and the number of drug holidays per 100 days ( no intake for > 48 h if once daily or for > 24 h if twice daily intake ) . Testing occurred by simple mixed logistic regression analysis . Factors significant after correction for multiple testing were entered into a multiple logistic regression model . Mean taking , dosing , timing adherence , and drug holidays were 98 % , 96 % , 93 % , and 1.1 days , respectively . Non‐adherence was associated with lower self‐efficacy , higher self‐reported non‐adherence , no pillbox usage , and male gender . Adherence declined between Monday and Sunday . This study provides a framework for identifying patients at risk for non‐adherence and for developing adherence‐enhancing interventions INTRODUCTION The aim of this study was to compare the effect of continuous care model with routine care on the quality of life among patients who receive a kidney transplant . MATERIAL S AND METHODS In a r and omized clinical trial , 90 kidney transplant patients were selected from 4 hospitals in Tehran , Iran , and were r and omly assigned to 2 group . In the experimental group , continuous care model was applied for 3 months and the control group received routine care . The scale scores of the Kidney Transplant Question naire concerning quality of life were monthly compared between the two groups . RESULTS Of 90 patients , 4 in the experimental and 8 in the control group were excluded from the study . Final analysis was performed on 41 in the experimental and 37 in the control groups . No significant difference was found between the two groups in terms of demographic variables . Although the quality of life scores increased in both groups , the mean scores of the experimental group were significantly higher than those in the control group at 1 , 2 , and 3 months . CONCLUSIONS Continuous care model may improve the kidney transplant patients ' quality of life OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : Output:

The literature used has shown that the population of kidney transplant patients is exposed to a high risk of psychiatric disorders with repercussions on the quality of life and the risk of rejection .

MS214174

***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 In COPD , functional status is improved by pulmonary rehabilitation ( PR ) but requires specific facilities . Tai Chi , which combines psychological treatment and physical exercise and requires no special equipment , is widely practice d in China and is becoming increasingly popular in the rest of the world . We hypothesized that Tai Chi is equivalent ( ie , difference less than ±4 St. George ’s Respiratory Question naire [ SGRQ ] points ) to PR . Methods A total of 120 patients ( mean FEV1 , 1.11 ± 0.42 L ; 43.6 % predicted ) bronchodilator‐naive patients were studied . Two weeks after starting indacaterol 150 & mgr;g once daily , they r and omly received either st and ard PR thrice weekly or group Tai Chi five times weekly , for 12 weeks . The primary end point was change in SGRQ prior to and following the exercise intervention ; measurements were also made 12 weeks after the end of the intervention . Results The between‐group difference for SGRQ at the end of the exercise interventions was –0.48 ( 95 % CI PR vs Tai Chi , –3.6 to 2.6 ; P = .76 ) , excluding a difference exceeding the minimal clinical ly important difference . Twelve weeks later , the between‐group difference for SGRQ was 4.5 ( 95 % CI , 1.9 to 7.0 ; P < .001 ) , favoring Tai Chi . Similar trends were observed for 6‐min walk distance ; no change in FEV1 was observed . Conclusions Tai Chi is equivalent to PR for improving SGRQ in COPD . Twelve weeks after exercise cessation , a clinical ly significant difference in SGRQ emerged favoring Tai Chi . Tai Chi is an appropriate substitute for PR . Trial Registry Clinical Trials.gov ; No. : NCT02665130 ; URL : www . clinical trials.gov BACKGROUND Although the benefits of exercise on the health of patients with chronic obstructive pulmonary disease ( COPD ) have been widely reported , the effect of Tai Chi as an alternative exercise has not been thoroughly evaluated in patients with COPD . This study reported a r and omised controlled trial , which investigated the effects of Tai Chi on lung function , exercise capacity , and diaphragm strength in patients with COPD . TRIAL DESIGN Single blind r and omised controlled study . SETTING Department of Respiratory Medicine , Xiangya Hospital , Central South University . METHODS Forty patients with COPD were r and omised into either a control group or Tai Chi intervention group . Participants in the control group received only routine care , while participants in the Tai Chi group received routine care and completed a six-month Tai Chi exercise program . OUTCOMES Lung function parameters , blood gas parameters , 6-min walking distance ( 6MWD ) , and diaphragm strength parameters . RESULTS Lung function parameters ( FEV1 : 1.43 ± 0.08 and FEV1 ( % ) predicted : 47.6 ± 4.76 ) , 6MWD ( 476 ± 15 ) and diaphragm strength parameters ( TwPes : 1.17 ± 0.07 , TwPga : -1.12 ± 0.06 , and TwPdi : 1.81 ± 0.09 ) were found to be significantly increased in participants who successfully completed the six-month Tai Chi program compared to participants in the control group who only received routine care ( p<0.05 ) . These parameters were also found to be significantly increased in participants who completed the Tai Chi exercise program compared to the baseline ( p<0.05 ) . In contrast , no significant differences in PaO2 and PaCO2 were observed in participants before or after completing a Tai Chi program or between Tai Chi group and control group ( p>0.05 ) . CONCLUSIONS Tai Chi enhances lung function , exercise capacity , and diaphragm strength . However , this is only preliminary research data and a larger trial is needed for more detailed results OBJECTIVE To determine the feasibility of a r and omized controlled trial of the effect of a tai chi program on quality of life and exercise capacity in patients with COPD . METHODS We r and omized 10 patients with moderate to severe COPD to 12 weeks of tai chi plus usual care ( n = 5 ) or usual care alone ( n = 5 ) . The tai chi training consisted of a 1-hour class , twice weekly , that emphasized gentle movement , relaxation , meditation , and breathing techniques . Exploratory outcomes included disease-specific symptoms and quality -of-life , exercise capacity , pulmonary function tests , mood , and self-efficacy . We also conducted qualitative interviews to capture patient narratives regarding their experience with tai chi . RESULTS The patients were willing to be r and omized . Among 4 of the 5 patients in the intervention group , adherence to the study protocol was excellent . The cohort 's baseline mean ± SD age , percent-of-predicted FEV₁ , and ratio of FEV₁ to forced vital capacity were 66 ± 6 y , 50 ± 12 % , and 0.63 ± 0.14 , respectively . At 12 weeks there was significant improvement in Chronic Respiratory Question naire score among the tai chi participants ( 1.4 ± 1.1 ) , compared to the usual-care group ( -0.1 ± 0.4 ) ( P = .03 ) . There were nonsignificant trends toward improvement in 6-min walk distance ( 55 ± 47 vs -13 ± 64 m , P = .09 ) , Center for Epidemiologic Studies Depression Scale ( -9.0 ± 9.1 vs -2.8 ± 4.3 , P = .20 ) , and University of California , San Diego Shortness of Breath score ( -7.8 ± 3.5 vs -1.2 ± 11 , P = .40 ) . There were no significant changes in either group 's peak oxygen uptake . CONCLUSIONS A r and omized controlled trial of tai chi is feasible in patients with moderate to severe COPD . Tai chi exercise as an adjunct to st and ard care warrants further investigation BACKGROUND Persons with chronic obstructive pulmonary disease ( COPD ) have reduced exercise capacity and levels of physical activity . Supervised , facility-based pulmonary rehabilitation programs improve exercise capacity and reduce dyspnea , but novel long-term strategies are needed to maintain the benefits gained . Mind-body modalities such as Tai Chi which combine aerobic activity , coordination of breathing , and cognitive techniques that alleviate the physical inactivity , dyspnea , and anxiety and depression that are the hallmarks of COPD are promising strategies . METHODS / DESIGN We have design ed a r and omized controlled study to examine whether Tai Chi will maintain exercise capacity in persons with COPD who have recently completed a supervised pulmonary rehabilitation program , compared to st and ard care . The primary outcome is 6-min walk test distance at 6 months . Secondary outcomes include health-related quality of life , dyspnea , mood , occurrence of acute exacerbations , engagement in physical activity , exercise self-efficacy , and exercise adherence . Simultaneously , we are conducting a pilot study of group walking . We will enroll 90 persons who will be r and omized to one of three arms in a 2:2:1 ratio : Tai Chi , st and ard care , or group-based walking . DISCUSSION The Long-term Exercise After Pulmonary Rehabilitation ( LEAP ) study is a novel and clinical ly relevant trial . We will enroll a well-characterized cohort of persons with COPD and will comprehensively assess physiological and psychosocial outcomes . Results of this study will provide the evidence base for persons with COPD to engage in Tai Chi as a low-cost , long-term modality to sustain physical activity in persons who have completed a st and ard short-term pulmonary rehabilitation program . TRIAL REGISTRATION This trial is registered in Clinical Trials.gov , with the ID number of NCT01998724 Objectives . To evaluate the sustaining effects of Tai Chi Qigong ( TCQ ) in improving the psychosocial health in chronic obstructive pulmonary disease ( COPD ) patients in the sixth month . Background . COPD affects both physical and emotional aspects of life . Measures to minimize patients ' suffering need to be implemented . Methods . 206 COPD patients were r and omly assigned into three groups : TCQ group , exercise group , and control group . The TCQ group completed a three-month TCQ program , the exercise group practice d breathing and walking exercise , and the control group received usual care . Results . Significant group-by-time interactions in quality of life ( QOL ) using St. George 's respiratory question naire ( P = 0.002 ) and the perceived social support from friends using multidimensional scale of perceived social support ( P = 0.04 ) were noted . Improvements were observed in the TCQ group only . Conclusions . TCQ has sustaining effects in improving psychosocial health ; it is also a useful and appropriate exercise for COPD patients The aims of the study were to determine the effect of short-form Sun-style t’ai chi ( SSTC ) ( part A ) and investigate exercise intensity of SSTC ( part B ) in people with chronic obstructive pulmonary disease ( COPD ) . Part A : after confirmation of eligibility , participants were r and omly allocated to either the t’ai chi group or control group ( usual medical care ) . Participants in the t’ai chi group trained twice weekly for 12 weeks . Part B : participants who had completed training in the t’ai chi group performed a peak exercise test ( incremental shuttle walk test ) and SSTC while oxygen consumption ( VO2 ) was measured . Exercise intensity of SSTC was determined by the per cent of VO2 reserve . Of 42 participants ( mean±sd forced expiratory volume in 1 s 59±16 % predicted ) , 38 completed part A and 15 completed part B. Compared to control , SSTC significantly increased endurance shuttle walk time ( mean difference 384 s , 95 % CI 186–510 ) ; reduced medial-lateral body sway in semi-t and em st and ( mean difference -12.4 mm , 95 % CI -21– -3 ) ; and increased total score on the chronic respiratory disease question naire ( mean difference 11 points , 95 % CI 4–18 ) . The exercise intensity of SSTC was 53±18 % of VO2 reserve . SSTC was an effective training modality in people with COPD achieving a moderate exercise intensity which meets the training recommendations Introduction Although pulmonary rehabilitation ( PR ) is associated with significant clinical benefits in chronic obstructive pulmonary disease ( COPD ) and has been recommended by guidelines , PR with conventional exercise training has not been widely applied in the clinic because of its inherent limitations . Alternative exercise such as Tai Chi has been investigated and the results are promising . However , the strengths and weaknesses of the exercise modality of Tai Chi , conventional PR and a combination of Tai Chi and conventional PR and the possible mechanisms underlying Tai Chi exercise remain unclear . This study aims to address the above research gaps in a well- design ed clinical trial . Methods and analysis This study is a single-blind , r and omised controlled trial . Participants with stable COPD will be recruited and r and omly assigned to one of four groups receiving Tai Chi exercise , conventional PR using a total body recumbent stepper ( TBRS ) , combined Tai Chi and TBRS , or usual care ( control ) in a 1:1:1:1 ratio . Participants will perform 30 min of supervised exercise three times a week for 8 weeks ; they will receive sequential follow-ups until 12 months after recruitment . The primary outcome will be health-related quality of life as measured by the St George 's Respiratory Question naire . Secondary outcomes will include 6 min walking distance , pulmonary function , the modified Medical Research Council Dyspnoea Scale , the COPD Assessment Test , the Hospital Anxiety and Depression Scale , the Berg Balance Scale , exacerbation frequency during the study period , and systemic inflammatory and immune markers . Ethics and dissemination Ethics approval has been granted by the Clinical Trial and Biomedical Ethics Committee of West China Hospital of Sichuan University ( No TCM-2015 - 82 ) . Written informed consent will be obtained from each participant before any procedures are performed . The study findings will be published in peer- review ed journals and presented at national and international conferences . Trial registration number ChiCTR-IOR-15006874 ; Pre- results OBJECTIVES To evaluate the sustaining effects of Tai chi Qigong in improving the physiological health for COPD patients at sixth month . DESIGN A r and omized controlled trial . Subjects were in three r and omly assigned groups : Tai chi Qigong group , exercise group , and control group . SETTING The 206 subjects were recruited from five general outpatient clinics . INTERVENTIONS Tai chi Qigong group completed a 3-month Tai chi Qigong program . Exercise group practice d breathing and walking as an exercise . Control group received usual care . MAIN OUTCOME MEASURES Primary outcomes included six-minute walking distance and lung functions . Secondary outcomes were dyspnea and fatigue levels , number of exacerbations and hospital admissions . RESULTS Tai chi Qigong group showed a steady improvement in exercise capacity ( P<.001 ) from baseline to the sixth month . The mean walking distance increased from 298 to 349 meters ( + 17 % ) . No significant changes were noted in the other two groups . Tai chi Qigong group also showed improvement in lung functions ( P<.001 ) . Mean forced expiratory volume in 1s increased from .89 to .99l ( + 11 % ) . No significant change was noted in the exercise group . Deterioration was found in the control group , with mean volume decreased from .89 to .84l ( -5.67 % ) . Sign Output:

Conclusions Tai Chi may represent an appropriate alternative or complement to st and ard rehabilitation programs .

MS214175

***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 It is unclear from prior reports whether the relationships between self-ratings of anxiety or emotional stress and parasympathetic nervous system components of heart rate variability are independent of personality and cardiorespiratory fitness . We examined those relationships in a clinical setting prior to a st and ardized exercise test . METHODS AND RESULTS Heart rate variability ( HRV ) was measured during 5 min of supine rest among 92 healthy men ( N=52 ) and women ( N=40 ) who had above-average cardiorespiratory fitness as indicated by peak oxygen uptake measured during grade -incremented treadmill exercise . HRV data sets were decomposed into low-frequency ( LF ; 0.05 - 0.15 Hz ) and high-frequency ( HF ; 0.15 - 0.5 Hz ) components using spectral analysis . Self-ratings of trait anxiety and perceived emotional stress during the past week were also assessed . CONCLUSIONS There was an inverse relationship between perceived emotional stress during the past week and the normalized HF component of HRV ( P=0.038 ) . This indicates a lower cardiac vagal component of HRV among men and women who perceived more stress . That relationship was independent of age , gender , trait anxiety , and cardiorespiratory fitness . It was also independent of heart rate ; mean arterial blood pressure ; and respiration rate , factors which can influence HRV and might be elevated among people reporting anxiety and perceived stress . We conclude that vagal modulation of heart period appears to be sensitive to the recent experience of persistent emotional stress , regardless of a person 's level of physical fitness and disposition toward experiencing anxiety PURPOSE We analyzed HR variability ( HRV ) to detect alterations in autonomic function that may be associated with functional overreaching ( F-OR ) in endurance athletes . METHODS Twenty-one trained male triathletes were r and omly assigned to either intensified training ( n = 13 ) or normal training ( n = 8) groups during 5 wk . HRV measures were taken daily during a 1-wk moderate training ( baseline ) , a 3-wk overload training , and a 1-wk taper . RESULTS All the subjects of the intensified training group demonstrated a decrease in maximal incremental running test performance at the end of the overload period ( -9.0 % ± 2.1 % of baseline value ) followed by a performance supercompensation after the taper and were therefore diagnosed as F-OR . According to a qualitative statistical analysis method , a likely to very likely negative effect of F-OR on HR was observed at rest in supine and st and ing positions , using isolated seventh-day values and weekly average values , respectively . When considering the values obtained once per week , no clear effect of F-OR on HRV parameters was found . In contrast , the weekly mean of each HRV parameter showed a larger change in indices of parasympathetic tone in the F-OR group than the control group in supine position ( with a 96%/4%/0 % chance to demonstrate a positive/trivial/negative effect on Ln RMSSD after the overload period ; 77%/22%/1 % on LnHF ) and st and ing position [ 98%/1%/1 % on Ln RMSSD ; 99%/0%/1 % on LnHF ; 95%/1%/4 % on Ln(LF + HF ) ] . During the taper , theses responses were reversed . CONCLUSIONS Using daily HRV recordings averaged over each week , this study detected a progressive increase in the parasympathetic modulation of HR in endurance athletes led to F-OR . It also revealed that due to a wide day-to-day variability , isolated , once per week HRV recordings may not detect training-induced autonomic modulations in F-OR athletes Purpose of this study was to test utility of heart rate variability ( HRV ) in daily endurance exercise prescriptions . Twenty-six healthy , moderately fit males were r and omized into predefined training group ( TRA , n = 8) , HRV-guided training group ( HRV , n = 9 ) , and control group ( n = 9 ) . Four-week training period consisted of running sessions lasting 40 min each at either low- or high-intensity level . TRA group trained on 6 days a week , with two sessions at low and four at high intensity . Individual training program for HRV group was based on individual changes in high-frequency R – R interval oscillations measured every morning . Increase or no change in HRV result ed in high-intensity training on that day . If there was significant decrease in HRV ( below reference value [ 10-day mean-SD ] or decreasing trend for 2 days ) , low-intensity training or rest was prescribed . Peak oxygen consumption ( VO2peak ) and maximal running velocity ( Loadmax ) were measured in maximal treadmill test before and after the training . In TRA group , Loadmax increased from 15.1 ± 1.3 to 15.7 ± 1.2 km h−1 ( P = 0.004 ) , whereas VO2peak did not change significantly ( 54 ± 4 pre and 55 ± 3 ml kg−1 min−1 post , P = 0.224 ) . In HRV group , significant increases were observed in both Loadmax ( from 15.5 ± 1.0 to 16.4 ± 1.0 km h−1 , P < 0.001 ) and VO2peak ( from 56 ± 4 to 60 ± 5 ml kg−1 min−1 , P = 0.002 ) . The change in Loadmax was significantly greater in HRV group compared to TRA group ( 0.5 ± 0.4 vs. 0.9 ± 0.2 km h−1 , P = 0.048 , adjusted for baseline values ) . No significant differences were observed in the changes of VO2peak between the groups . We concluded that cardiorespiratory fitness can be improved effectively by using HRV for daily training prescription Daily aerobic training results in autonomic control of the heart toward vagal dominance . The constancy of vagal dominance after controlled training followed by a home-based training program in accordance with contemporary guidelines is not known . We set out here to study whether the vagal dominance induced by 8 weeks of controlled aerobic training is preserved after a 10-month home-based training program . For the controlled study , healthy men were r and omized as training ( n=18 ) and control subjects ( n=6 ) . The training was started by a supervised 8-week period with six training sessions a week [ 45 ( 15 ) min each ] at an intensity of 70–80 % of maximum heart rate , followed by a home-based training program for 10 months in accordance with the American College of Sports Medicine recommendations . Cardiovascular autonomic function was assessed by analyzing HR variability over a 24-h period and separately during the night hours ( midnight–6 a.m. ) . Maximal running performance improved during the controlled training 16 (7)% ( range 4–31 % , P<0.001 ) and remained 8 (8)% ( range −3 to 23 % , P<0.001 ) above the baseline level after the home-based training program . At night , the vagally mediated high-frequency ( HF ) power of R-R intervals increased during the controlled training from 6.7 ( 1.3 ) to 7.3 ( 1.1 ) ln ms2 ( P<0.001 ) and remained higher than the baseline after the home-based training [ 7.0 ( 1.3 ) ln ms2 , P<0.05 ] . The changes in running performance correlated with the changes in HF power at night ( r=0.41 , P<0.05 ) and over 24 h ( r=0.44 , P<0.05 ) after the home-based training program . Similarly , the changes in body mass index correlated with the changes in HF power over 24 h ( r=−0.44 , P<0.05 ) after the home-based training program . The high vagal outflow to the heart after the home-based training is associated with good physical performance and body mass control OBJECTIVES Heart rate kinetics are faster in well-trained athletes at exercise onset , indicating sensitivity to training status , but whether they track performance changes due to changes in training load is unknown . DESIGN R and omised , counterbalanced , cross-over . METHODS 17 cyclists completed two weeks of light and two weeks of heavy training . The day after each training period heart rate was recorded during 5 min cycling at 100 W to determine the maximal rate of heart rate increase . Participants then performed a 5 min cycle time-trial after which heart rate recovery was determined . RESULTS Work during 5 min cycle time-trial decreased 3.5 % ( P<0.04 ) in participants ( n=8 ) who increased training load ( completed light training then heavy training ) and , although maximal rate of heart rate increase did not change ( P=0.27 ) , within-individual changes in work were correlated with changes in maximal rate of heart rate increase ( r=0.87 , P=0.005 ) . Work during 5 min cycle time-trial increased 6.5 % ( P<0.001 ) in 9 participants who decreased training load ( completed heavy training then light training ) and maximal rate of heart rate increase increased 28 % ( P=0.002 ) but the changes in maximal work were not related to changes in rate of heart rate increase ( r=0.32 , P=0.40 ) . Heart rate recovery tended to track changes in 5 min cycle time-trial work following increases and decreases in training load ( r=0.65 - 0.75 , P=0.03 - 0.08 ) . CONCLUSIONS Maximal rate of heart rate increases during cycling at 100 W tracks reductions in exercise performance when training load is increased , but not performance improvements when training loads are reduced . Maximal rate of heart rate increase may be a useful adjunct to heart rate recovery for tracking changes in exercise performance 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 The effects of intensified training in combination with a reduced training volume on muscle ion kinetics , transporters , and work capacity were examined . Eight well-trained cyclists replaced their regular training with speed-endurance training ( 12 × 30 s sprints ) 2 - 3 times per week and aerobic high-intensity training ( 4 - 5 × 3 - 4 min at 90 - 100 % of maximal heart rate ) 1 - 2 times per week for 7 wk and reduced training volume by 70 % ( intervention period ; IP ) . The duration of an intense exhaustive cycling bout ( EX2 ; 368 ± 6 W ) , performed 2.5 min after a 2-min intense cycle bout ( EX1 ) , was longer ( P < 0.05 ) after than before IP ( 4:16 ± 0:34 vs. 3:37 ± 0:28 min : s ) , and mean and peak power during a repeated sprint test improved ( P < 0.05 ) by 4 % and 3 % , respectively . Femoral venous K(+ ) concentration in recovery from EX1 and EX2 was lowered ( P < 0.05 ) after compared with before IP , whereas muscle interstitial K(+ ) concentration and net muscle K(+ ) release during exercise was unaltered . No changes in muscle lactate and H(+ ) release during and after EX1 and EX2 were observed , but the in vivo buffer capacity was higher ( P < 0.05 ) after IP . Expression of the ATP-sensitive K(+ ) ( KATP ) channel ( Kir6.2 ) decreased by IP , with no change in the strong inward rectifying K(+ ) channel ( Kir2.1 ) , muscle Na(+)-K(+ ) pump subunits , monocarboxylate transporters 1 and 4 ( MCT1 and MCT4 ) , and Na(+)/H(+ ) exchanger 1 ( NHE1 ) . In conclusion , 7 wk of intensified training with a reduced training volume improved performance during repeated intense exercise , which was associated with a greater muscle reuptake of K(+ ) and muscle buffer capacity but not with the amount of muscle ion transporters Numerous symptoms have been associated with the overtraining syndrome ( OT ) , including changes in autonomic function . Heart rate variability ( HRV ) provides non‐invasive data about the autonomic regulation of heart rate in real‐life conditions . The aims of the study were to : ( i ) characterize the HRV profile of seven athletes ( OA ) diagnosed as suffering of OT , compared with eight healthy sedentary ( C ) and eight trained ( T ) subjects during supine rest and 60 ° upright , and ( ii ) compare the traditional time‐ and frequency‐domain analysis assessment of HRV with the non‐linear Poincaré plot analysis . In the latter each R‐R interval is plotted as a function of the previous one , and the st and ard deviations of the instantaneous ( SD1 ) and long‐term R‐R interval variability are calculated . Total power was higher in T than in C and OA both in supine ( 1158 ± 1137 , 6092 ± 3554 and 2970 ± 2947 ms2 for C , T and OA , respectively ) and in upright ( 640 ± 499 , 1814 ± 806 and 1092 ± 712 ms2 for C , T and OA , respectively ; P<0·05 ) positions . In supine position , indicators of parasympathetic activity to the sinus node were higher in T compared with C and OA ( high‐frequency power : 419·1 ± 381·2 , 1 Output:

Conclusions Increases in vagal-related indices of resting and post-exercise HRV , post-exercise HRR , and HR acceleration are evident when positive adaptation to training has occurred , allowing for increases in performance . However , increases in post-exercise HRV and HRR also occur in response to overreaching , demonstrating that additional measures of training tolerance may be required to determine whether training-induced changes in these parameters are related to positive or negative adaptations . Resting HRV is largely unaffected by overreaching , although this may be the result of method ological issues that warrant further investigation . HR acceleration appears to decrease in response to overreaching training , and thus may be a potential indicator of training-induced fatigue

MS214176

***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 —With MRI , an index of myocardial perfusion reserve ( MPRI ) can be determined . We assessed the value of this technique for the noninvasive detection of coronary artery disease ( CAD ) in patients with suspected CAD . Methods and Results —Eighty-four patients referred for a primary diagnostic coronary angiography were examined with a 1.5 T MRI tomograph ( Philips-ACS ) . For each heartbeat , 5 slices were acquired during the first pass of 0.025 mmol gadolinium-diethylenetriamine pentaacetic acid/kg body weight before and during adenosine vasodilation by using a turbo-gradient echo/echo-planar imaging-hybrid sequence . MPRI was determined from the alteration of the upslope of the myocardial signal intensity curves for 6 equiangular segments per slice . Receiver operating characteristics were performed for different criteria to differentiate ischemic and nonischemic segments . Prevalence of CAD was 51 % . Best results were achieved when only the 3 inner slices were assessed and a threshold value of 1.1 was used for the second smallest value as a marker for significant CAD . This approach yielded a sensitivity of 88 % , specificity of 90 % , and accuracy of 89 % . Conclusion —The determination of MPRI with MRI yields a high diagnostic accuracy in patients with suspected CAD Summary Background Real world cardiology is faced with a low diagnostic yield of coronary angiography ( CXA ) in patients presenting with ACC/AHA class II CXA indication . Our aim was to analyze the clinical implication of a Cardiac MR ( CMR ) protocol including adenosine stress perfusion in this patient population . We examined whether CMR could enhance appropriate CXA indication and thus reduce the rate of pure diagnostic CXA . In addition , we compared the relative impact of CMR exam components ( perfusion , function and viability assessment ) in achieving this target . Methods 176 patients were referred for CXA with class II indication . 171 underwent complete additional CMR exam in a 1.5-T whole body CMR-scanner for myocardial function , ischemia and viability prior to CXA . The routine protocol for assessment of CAD consisted of functional imaging ( long and short axes ) , adenosine stress- and rest-perfusion in short axis orientation and “ late enhancement ” imaging in long and short axes . Images were analyzed by two independent and blinded investigators . Interobserver differences were resolved by a third reader . Results There was a high association between CMR results and subsequent invasive findings ( chi square for CMR perfusion deficit and stenosis > 70 % in CXA : 113.7 , p<0.0001 ) . 109 ( 63.7 % ) of our patients had relevant perfusion deficits as seen by CMR and matching coronary artery stenosis > 70 % . Four ( 2.3 % ) patients had false negative CMR findings . In 58 patients ( 33.9 % ) no relevant coronary artery stenosis could be observed , correctly predicted by CMR in 48 cases ; in 10 ( 5.8 % ) patients CMR provided false positive results . Sensitivity of CMR to detect relevant CAD ( > 70 % luminal narrowing ) was 0.96 , specificity 0.83 , positive predictive value 0.92 and negative predictive value 0.92 . Of the CMR components , perfusion deficit was the strongest independent predictor ( odds ratio 132.3 , p < 0.0001 ) . Conclusion In a great number of patients being referred to cath lab with ACC/AHA class II indication for CXA , CMR provides a high accuracy for decision making regarding appropriateness of the invasive exam . CMR prior to CXA could substantially reduce pure diagnostic coronary angiographies in patients with intermediate probability for CAD , in our patient-cohort from approximately 34 % to 6 % . Further studies are warranted to identify rare false negative CMR results BACKGROUND Qualitative interpretation of myocardial contrast echocardiography ( MCE ) improves the accuracy of wall-motion analysis for assessment of coronary artery disease ( CAD ) . We examined the feasibility and accuracy of quantitative MCE for diagnosis of CAD . METHODS Dipyridamole/exercise stress MCE ( destruction-replenishment protocol with real-time imaging ) was performed in 90 patients undergoing quantitative coronary angiography , 48 of whom had significant ( > 50 % ) stenoses . MCE was repeated with exercise alone in 18 patients . Myocardial blood flow ( A*beta ) was obtained from blood volume ( A ) and time to refill ( beta ) . RESULTS Quantification of flow reserve was feasible in 88 % . The mean A*beta reserve in the anterior wall was significantly impaired for patients with left anterior descending coronary artery disease ( n = 28 ) compared with those with no disease ( 1.6 + /- 1.2 vs 4.0 + /- 2.5 , P < or = .001 ) . This reflected impaired beta reserve , with no difference in the A reserve . Applying a receiver operating characteristic curve derived cutoff of 2.0 for A*beta reserve , quantitative MCE was 76 % sensitive and 71 % specific for the diagnosis of significant left anterior descending coronary artery stenosis . Posterior circulation results were similar , with 78 % sensitivity and 59 % specificity for detection of posterior CAD . Overall , quantitative MCE was similarly sensitive to qualitative approach for diagnosis of CAD ( 88 % vs 93 % ) , but with lower specificity ( 52 % vs 65 % , P = .07 ) . In 18 patients restudied with pure exercise stress , the mean myocardial blood flow reserve was less than after combined stress ( 2.1 + /- 1.6 vs 3.7 + /- 1.9 , P = .01 ) . CONCLUSION Quantitative MCE is feasible for the diagnosis of CAD with dipyridamole/exercise stress . Dipyridamole prolongs postexercise hyperemia , augmenting the degree of hyperemia at the time of imaging To investigate prospect ively , in patients with suspicion of coronary artery disease ( CAD ) , the added value of coronary calcium scoring ( CS ) as adjunct to cardiac magnetic resonance ( CMR ) for the diagnosis of morphological coronary stenosis in comparison to catheter angiography ( CA ) . Sixty consecutive patients ( 8 women ; 64 ± 10 years ) referred to CA underwent CMR ( 1.5 T ) including perfusion and late gadolinium-enhancement imaging as well as CS with computed tomography . Diagnostic performance was evaluated for CMR and CS separately , and for both methods combined , with CA as reference st and ard . Best CS threshold combined with a specificity > 90 % to predict significant stenosis in patients without abnormalities on CMR was determined from receiver operator characteristics ( ROC ) analysis . Abnormal CMR results were considered to indicate significant stenosis regardless of CS ; CS above threshold reclassified patients to have CAD regardless of CMR . CA identified 104/960 ( 11 % ) coronary segments with coronary artery stenosis > 50 % in 36/60 ( 60 % ) patients . ROC revealed an area-under-the-curve of 0.83 ( 95%CI : 0.68 - 0.99 ) with the best CS threshold of 495 Agatston score ( sensitivity 50 % ) . CMR depicted 128/960 ( 13 % ) myocardial segments with abnormalities in 31/60 ( 52 % ) patients . Sensitivity , specificity , negative ( NPV ) and positive predictive value ( PPV ) of CMR were 78 , 88 , 72 and 90 % . When adding CS to CMR , sensitivity and NPV increased to 89 and 83 % , while specificity and PPV slightly decreased to 83 and 89 % . Accuracy of the combined approach ( 87 % ) was significantly ( P < 0.05 ) higher than that of CMR ( 82 % ) alone . Adding CS to CMR improves the accuracy for the detection of morphological CAD UNLABELLED The purpose of this study was to prospect ively evaluate the diagnostic accuracy of a cardiovascular magnetic resonance ( MR ) k-space and time ( k-t ) broad-use linear acquisition speed-up technique ( BLAST ) accelerated perfusion sequence for depicting clinical ly relevant coronary artery disease ( CAD ) , with use of coronary angiography as the reference st and ard . The local ethics committee approved this study , and informed consent was obtained from 40 patients ( 28 men , 12 women ; mean age , 61 years + /- 8 [ st and ard deviation ] ) scheduled for coronary catheterization . A balanced steady-state free precession pulse sequence ( 2.6 x 2.6 x 10 mm ) with a net k-t acceleration factor of 3.8 ( repetition time msec/echo time msec , 3.2/1.6 ; flip angle , 50 degrees ) was applied . Visual analysis of perfusion images and quantitative analysis of signal-time curves obtained in the myocardium were performed by using segmental myocardial upslope , peak enhancement , and their respective ratios . Visual analysis revealed sensitivity , specificity , and diagnostic accuracy of 86 % , 78 % , and 83 % , respectively , in the detection of coronary stenoses with at least 50 % luminal narrowing . Significant ( P < .05 ) changes between ischemic and remote segments could be shown for all perfusion indexes applied . Use of myocardial perfusion imaging with k-t BLAST for accelerated data acquisition is feasible in the identification of patients with substantial CAD ( coronary stenosis > or= 50 % ) . SUPPLEMENTAL MATERIAL http://radiology.rsnajnls.org/cgi/content/full/245/3/863/DC1 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 Myocardial flow reserve ( MFR ) is not routinely assessed in myocardial perfusion imaging ( MPI ) studies but has been hypothesized to affect test accuracy when assessing disease severity by coronary vessel lumenography . Magnetic resonance imaging ( MRI ) is an emerging diagnostic technique that can both perform MPI and assess MFR . We studied women ( n = 184 ) enrolled in the Women 's Ischemia Syndrome Evaluation ( WISE ) study with symptoms suggesting ischemic heart disease . Tests performed were coronary angiography and MPI by both MR and gated radionuclide single photon emission computed tomography ( gated-SPECT ) . The MFR index was calculated using the MR data acquired at baseline and under vasodilation ( dipyridamole ) conditions . The study was structured with a pilot and an implementation phase . During the pilot phase ( n = 46 ) data were unmasked and an MFR threshold was defined to divide patients into those with an adequate ( AMFRI ) or inadequate ( IMFRI ) MFR index . During the implementation phase , the MFR index threshold was prospect ively applied to patients ( n = 138 ) . In the implementation phase , MPI ischemia detection accuracy compared to severe ( > or = 70 % ) coronary artery diameter narrowing by angiography was higher in the AMFRI vs. the IMFRI group for MRI ( 86 % vs. 70 % , p < 0.05 ) and gated-SPECT ( 89 % vs. 67 % , p < 0.01 ) . The IMFRI group ( n = 55 , 30 % of study population ) had a higher resting rate-pressure product compared with the AMFRI group ( 10,599 + /- 2871 vs. Output:

Conclusion Our results suggest that MRI is superior for the diagnosis of obstructive CAD compared with ECHO and SPECT . ECHO and SPECT demonstrated similar diagnostic performance . Key Points• MRI can assess myocardial perfusion.• MR perfusion diagnoses coronary artery disease better than echocardiography or SPECT.• Echocardiography and SPECT have similar diagnostic performance.• MRI can save coronary artery disease patients from more invasive tests.• MRI and SPECT show evidence of publication bias , implying possible overestimation

MS214177

***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 propose a hypothesis that differences in base excision repair capacity modulate the effect of dietary antioxidant intake on prostate cancer risk . As a preliminary test of this hypothesis , we conducted a pilot case-control study to evaluate prostate cancer risk in men with polymorphisms in the XRCC1 gene , a key player in base excision repair , across different strata of antioxidant intake . Seventy-seven prostate cancer patients and 183 community controls , for whom we have detailed dietary information , were frequency matched on age and race . We found a somewhat lower prostate cancer risk for men with one or two copies of the variant alleles at the XRCC1 codons 194 and 399 than for those who were homozygous for the common allele [ codon 194 : odds ratio ( OR ) = 0.8 ; 95 % confidence interval ( CI ) , 0.4 - 1.8 and codon 399 : OR = 0.8 ; 95 % CI , 0.5 - 1.3 ] . The variant at codon 280 was associated with a slightly increased prostate cancer risk ( OR = 1.5 ; 95 % CI , 0.7 - 3.6 ) . Only the codon 399 polymorphism occurred frequently enough to investigate its joint effect with antioxidant intake . Prostate cancer risk was highest among men who were homozygous for the common allele at codon 399 and had low dietary intake of vitamin E ( OR = 2.4 ; 95 % CI , 1.0 - 5.6 ) or lycopene ( OR = 2.0 ; 95 % CI , 0.8 - 4.9 ) , whereas low intake of these antioxidants in men without this genotype hardly increased prostate cancer risk . The polymorphism did not modulate risk associated with low intake of vitamin C , A , or beta-carotene . The data give some support for our hypothesis but should be regarded as preliminary , because it is limited by small sample size . We discuss what kind of data and what kind of studies are needed for future evaluation of this hypothesis As part of a population -based case-control study in Shanghai , China , we investigated whether variants in several DNA repair genes , either alone or in conjunction with other risk factors , are associated with prostate cancer risk . Genomic DNA from 162 patients newly diagnosed with prostate cancer and 251 healthy men r and omly selected from the population were typed for five nonsynonymous DNA repair markers . We found that the XRCC1-Arg399Gln AA and the MGMT-Leu84Phe CT+TT genotypes were associated with an increased risk of prostate cancer [ odds ratio ( OR ) , 2.18 ; 95 % confidence interval ( CI ) , 0.99 - 4.81 and OR , 1.99 ; 95 % CI , 1.19 - 3.34 , respectively ] . In contrast , XRCC3-Thr241Met , XPD-Lys751Gln , and MGMT-Ile143Val markers showed no significant associations with risk , although due to the much lower frequency of their variant alleles in this population we can not rule out small to modest effects . There was a significant interaction between the MGMT-84 marker and insulin resistance ( Pinteraction = 0.046 ) . Relative to men with the MGMT-84 CC genotype and a low insulin resistance ( < 0.097 ) , those having the CT-TT genotype and a greater insulin resistance had a 5.4-fold risk ( OR , 5.39 ; 95 % CI , 2.46 - 11.82 ) . In addition , for the XRCC3 - 241 marker , relative to men with the CC genotype and a low intake of preserved foods ( < 12.7 g/d ) , those harboring the CT+TT genotype and having a higher intake of preserved foods ( > 12.7 g/d ) , which contain nitrosamines and nitrosamine precursors , had a significantly increased risk of prostate cancer risk ( OR , 2.62 ; 95 % CI , 1.13 - 6.06 ) . In contrast , men with the CT+TT genotype and a low intake of preserved foods had a 69 % reduction in risk ( OR , 0.31 ; 95 % CI , 0.10 - 0.96 ; Pinteraction = 0.005 ) . These results suggest that genetic variants in the DNA repair pathways may be involved in prostate cancer etiology and that other risk factors , including preserved foods and insulin resistance , may modulate prostate cancer risk in combination with genetic susceptibility in these repair pathways . Replication in larger studies is necessary to preclude chance findings , particularly those among subgroups , and clarify the mechanisms involved DNA repair gene alterations have been shown to cause a reduction in DNA repair capacity and may influence an individual 's susceptibility to carcinogenesis . Single nucleotide polymorphisms ( SNPs ) of DNA repair genes have been shown to cause a reduction in repair activity . We hypothesized that SNPs of DNA repair genes may be a risk factor for renal cell carcinoma ( RCC ) . To test this hypothesis , DNA sample s from 112 cases of renal cell cancer and healthy controls ( n=180 ) were analyzed by PCR-RFLP to determine the genotypic frequency of six different polymorphic loci on five DNA repair genes ( XRCC1 , XPC , ERCC1 , XRCC3 , and XRCC7 ) . The chi(2 ) test was applied to compare the genotype frequency between patients and controls . We found that the frequency of 399Gln variant at XRCC1 Arg399Gln was significantly higher in RCC cases than in controls ( OR=2.83 , 95%CI=1.24 - 6.49 , P=0.01 ) . The frequency of T-A haplotype of XRCC1 194 Trp and XRCC1 399Gln was significantly higher in RCC than controls . No differences in genotypes were observed at the other sites . This is the first report on SNPs of DNA repair genes in renal cell carcinoma that suggests XRCC1 399Gln polymorphism may be a risk factor for RCC . Our present data suggest that the XRCC1 399Gln allele may be linked to susceptibility for RCC Environmental carcinogens contained in air pollution , such as polycyclic aromatic hydrocarbons , aromatic amines or N-nitroso compounds , predominantly form DNA adducts but can also generate interstr and cross-links and reactive oxygen species . If unrepaired , such lesions increase the risk of somatic mutations and cancer . Our study investigated the relationships between 22 polymorphisms ( and their haplotypes ) in 16 DNA repair genes belonging to different repair pathways in 1094 controls and 567 cancer cases ( bladder cancer , 131 ; lung cancer , 134 ; oral-pharyngeal cancer , 41 ; laryngeal cancer , 47 ; leukaemia , 179 ; death from emphysema and chronic obstructive pulmonary disease , 84 ) . The design was a case-control study nested within a prospect i ve investigation . Among the many comparisons , few polymorphisms were associated with the diseases at the univariate analysis : XRCC1 - 399 Gln/Gln variant homozygotes [ odds ratios ( OR ) = 2.20 , 95 % confidence intervals ( CI ) = 1.16 - 4.17 ] and XRCC3 - 241 Met/Met homozygotes ( OR = 0.51 , 95 % CI = 0.27 - 0.96 ) and leukaemia . The recessive model in the stepwise multivariate analysis revealed a possible protective effect of XRCC1 - 399Gln/Gln in lung cancer ( OR = 0.22 , 95 % CI = 0.05 - 0.98 ) , and confirmed an opposite effect ( OR = 2.47 , 95 % CI = 1.02 - 6.02 ) in the leukaemia group . Our results also suggest that the XPD/ERCC1-GAT haplotype may modulate leukaemia ( OR = 1.28 , 95 % CI = 1.02 - 1.61 ) , bladder cancer ( OR = 1.38 , 95 % CI = 1.06 - 1.79 ) and possibly other cancer risks . Further investigations of the combined effects of polymorphisms within these DNA repair genes , smoking and other risk factors may help to clarify the influence of genetic variation in the carcinogenic process Output:

We identified that XRCC1-rs25489 polymorphism was associated with an increased risk of urological neoplasms in heterozygote and dominant models . Moreover , in the subgroup analysis by cancer type , we found that XRCC1-rs25489 polymorphism was associated with an increased risk of bladder cancer ( BC ) in heterozygote model . Although overall analyses suggested a null result for XRCC1-rs25487 polymorphism , in the stratified analysis by ethnicity , an increased risk of urological neoplasms for Asians in allelic and homozygote models was identified . While for other polymorphisms in XRCC genes , no significant association was uncovered . To sum up , our results indicated that XRCC1-rs25489 polymorphism is a risk factor for urological neoplasms , particularly for BC .

MS214178

***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 Antithyroid drugs are effective in patients with hyperthyroidism due to Graves ' disease , but the rate of recurrence after treatment is high . In a recent Japanese study , adjunctive treatment with thyroxine ( T4 ) was associated with a recurrence rate 20 times lower than that among patients who received only an antithyroid drug . If these results are confirmed , combined therapy with an antithyroid drug and T4 might become the treatment of choice for all patients with Graves ' hyperthyroidism . METHODS We treated 111 patients ( 89 women and 22 men ) who had Graves ' hyperthyroidism . All patients initially received 40 mg of carbimazole daily for one month . Then one group received carbimazole alone for 17 months ( 52 patients ) , and the other group received carbimazole plus T4 for 17 months and T4 alone for 18 months ( 59 patients ) . In the carbimazole group , the dose was adjusted after one month to maintain a normal serum thyrotropin concentration . In the carbimazole-T4 group , the dose of carbimazole was not changed , but 100 micrograms of T4 per day was added to the regimen and the dose was adjusted to maintain an undetectable serum thyrotropin concentration ( < 0.04 microU per milliliter ) . RESULTS At the time of our analysis , 53 of the 111 patients had completed at least 3 months of follow-up ( median , 12 months ) after carbimazole was withdrawn . Hyperthyroidism recurred in eight patients in each group after a mean ( + /- SD ) of 6 + /- 4 months in the carbimazole group and 7 + /- 4 months in the carbimazole-T4 group . There was no difference between the recurrence rates in the two groups , despite the fact that serum thyrotropin concentrations were undetectable in 73 percent of patients in the carbimazole-T4 group on at least 75 percent of their visits . CONCLUSIONS The administration of T4 to patients with Graves ' disease during carbimazole treatment and after its withdrawal neither delays nor prevents the recurrence of hyperthyroidism BACKGROUND Antibodies to thyroid-stimulating hormone ( TSH ) receptors that stimulate the thyroid gl and cause hyperthyroidism in patients with Graves ' disease , and their production during antithyroid drug treatment is an important determinant of the course of the disease . One factor that might contribute to the persistent production of antibodies to TSH receptors is stimulation of the release of thyroid antigens by TSH during antithyroid drug therapy . We therefore studied the effect of the suppression of TSH secretion by thyroxine on the levels of antibodies to TSH receptors after thyroid hormone secretion had been normalized by methimazole . METHODS AND RESULTS The levels of antibodies to TSH receptors were measured during treatment with methimazole , either alone or in combination with thyroxine , in 109 patients with hyperthyroidism due to Graves ' disease . The patients first received 30 mg of methimazole daily for six months . All were euthyroid after six months , and their mean ( + /- SD ) level of antibodies to TSH receptors decreased from 64 + /- 9 percent to 25 + /- 15 percent ( P less than 0.01 ; normal , 2.9 + /- 1.4 percent ) . Sixty patients then received 100 micrograms of thyroxine and 10 mg of methimazole and 49 received placebo and 10 mg of methimazole daily for one year . In the thyroxine-treated group , the mean serum thyroxine concentration increased from 108 + /- 16 nmol per liter to 145 + /- 11 nmol per liter ( P less than 0.01 ) , and the level of antibodies to TSH receptors decreased from 28 + /- 10 percent to 10 + /- 3 percent after one month of combination therapy . In the patients who received placebo and methimazole , the mean serum thyroxine concentration decreased and the level of antibodies to TSH receptors did not change . Methimazole , but not thyroxine or placebo , was discontinued in each group 1 1/2 years after the beginning of treatment . The level of antibodies to TSH receptors further decreased ( from 6.6 + /- 3.2 percent at the time methimazole was discontinued to 2.1 + /- 1.2 percent one year later ) in the patients who continued to receive thyroxine , but it increased ( from 9.1 + /- 4.8 percent to 17.3 + /- 5.8 percent during the same period ) in the patients who received placebo . One patient in the thyroxine-treated group ( 1.7 percent ) and 17 patients in the placebo group ( 34.7 percent ) had recurrences of hyperthyroidism within three years after the discontinuation of methimazole . CONCLUSIONS The administration of thyroxine during antithyroid drug treatment decreases both the production of antibodies to TSH receptors and the frequency of recurrence of hyperthyroidism Antithyroid drugs are effective in restoring euthyroidism in Graves ' disease , but many patients experience relapse after withdrawal . Prevention of recurrence would therefore be a desirable goal . In a prospect i ve study , patients with successful outcome of 12 to 15 months antithyroid drug therapy were stratified for risk factors and r and omly assigned to receive levothyroxine in a variable thyrotropin (TSH)-suppressive dose for 2 years or no treatment . The levothyroxine group was r and omized to continue or discontinue levothyroxine after 1 year . End points included relapse of overt hyperthyroidism . Of 346 patients with Graves ' disease enrolled 225 were euthyroid 4 weeks after antithyroid drug withdrawal and were r and omly assigned to receive levothyroxine ( 114 patients ) or no treatment ( controls , 111 patients ) . Of those not r and omized , 39 patients showed early relapse within 4 weeks , 61 endogenous TSH suppression , 7 TSH elevation , and 14 had to be excluded . Dropout rate during the study were 13.3 % . Kaplan-Meier analyses showed relapse rates to be similar in the levothyroxine group ( 20 % after 1 year , 32 % after 2 years ) and the r and omized controls ( 18 % , 24 % ) , whereas relapses were significantly more frequent in the follow-up group of patients with endogenously suppressed TSH ( 33 % , 49 % ) . Levothyroxine therapy did not influence TSH-receptor antibody , nor did it reduce goiter size . The best prognostic marker available was basal TSH determined 4 weeks after withdrawal of antithyroid drugs ( posttreatment TSH ) . The study demonstrates that levothyroxine does not prevent relapse of hyperthyroidism after successful restoration of euthyroid function by antithyroid drugs and characterizes posttreatment TSH as a main prognostic marker Although antithyroid drugs ( ATD ) are widely used in the treatment of Graves ' disease , management protocol s , especially treatment duration , remain a subject of debate . The rate of relapse after short‐term regimens of less than 6 months with ATD at decreasing doses is higher than after longer treatments from 12 to 24 months . As no prospect i ve study has provided data on even longer protocol s exceeding 2 years , we conducted a prospect i ve trial to determine potential benefits of a 42‐month treatment compared with an 18‐month treatment Medical treatment of Graves ' disease involves antithyroid drugs with or without the addition of exogenous T4 . There have been conflicting reports as to whether the addition of T4 improves remission rates or delays relapse . To evaluate this issue in a North American population , 199 patients were treated with methimazole until they were euthyroid . They were then r and omized to either methimazole alone in a dose sufficient to normalize TSH ( group 1 ) , or to 30 mg methimazole daily plus sufficient T4 to maintain TSH in the upper normal range ( group 2 ) , or to 30 mg methimazole daily plus sufficient T4 to suppress TSH below 0.6 mIU/L ( group 3 ) . After 18 months , methimazole was stopped , and T4 was continued in groups 2 and 3 . Because not all patients in groups 2 and 3 achieved their target TSH concentration , they were reassigned to group A ( TSH > or = 1.0 ) or group B ( TSH < 1.0 ) , based on the mean TSH achieved during methimazole treatment . One hundred forty-nine patients have been followed for at least 6 months after stopping methimazole ( mean 27 months ) . Fifty-eight percent of patients have relapsed . There were no significant differences in relapse rates after stopping methimazole . Among those patients who did relapse , however , there was a significant difference in the months to relapse after stopping methimazole between groups B and 1 ( group 1 : 3.3 + /- 0.7 , group A : 5.6 + /- 0.8 , group B : 7.4 + /- 1.7 ; P = 0.01 for the comparison between groups B and 1 ) . We conclude that the addition of T4 to methimazole does not improve long-term remission rates in Graves ' disease A prospect i ve r and omized study was performed in patients with hyperthyroid Graves ' disease ( GD ) in order to compare long ( 18 months ) and short term ( 6 months ) antithyroid drug treatment on the remission rate . A therapeutic protocol was offered to all GD patients who had not been treated for this disease previously . All patients studied who followed the protocol were rechecked 2 yr after treatment was withdrawn , or earlier in the case of relapse . Of the patients having undergone long term treatment , 61.8 % still were in remission 2 yr after treatment withdrawal , whereas only 41.7 % of the patients treated for 6 months were in remission ( P less than 0.05 ) . Such findings clearly establish that treatment duration has a direct beneficial incidence on the remission rate . These results were confirmed by the fact that treatment for 18 months result ed in remission in 7 of 15 patients who had previously relapsed after a 6-month course of therapy . This improvement in relation to treatment duration might be due to the immunosuppressive action of carbimazole . No significant difference was observed between relapse and remission groups , regardless of treatment duration , for HLA ABDr , serum T3 and T4 , and T3/T4 ratio determined before treatment . Only the thyroid-stimulating antibody levels determined at the time of diagnosis and at the end of treatment were higher in the relapse group , a difference that was relevant only globally , due to value scattering . Furthermore , thyroid-stimulating antibody levels at the end of treatment may indicate remission or , conversely , continuance of the pathological process . ( ABSTRACT TRUNCATED AT 250 WORDS Sixty patients with Graves ' disease ( GD ) hyperthyroidism were distributed in two r and omized groups . Patients in group A ( n = 30 ) received carbimazole by a titration regimen , and patients in group B ( n = 30 ) were treated with higher doses of carbimazole plus T4 . Clinical and analytical evaluations were done at baseline , during treatment ( 18.4 + /- 2.6 months ) , and after , until the relapse of hyperthyroidism , or for 4.98 + /- 1.6 yr in patients who did not relapse . There were no differences in clinical parameters , thyroid hormones , or TSH binding inhibitory immunoglobulins ( TBII ) levels between the two groups , either at baseline or at the end of treatment . Serum TSH persisted undetectable in 16 out of 60 patients ( group A : 9 ; group B : 7 ) , after treatment . Relapse occurred in 38 patients ( 63.3 % ) , ( group A : 18 ( 60 % ) vs. group B : 20 ( 66.7 % ) ) . Patients who relapsed had bigger goiters at baseline ( P = 0.02 ) and at the end of treatment ( P = 0.03 ) . Eighty-seven percent ( 14/16 ) of patients with undetectable TSH after therapy relapsed , vs. 54.5 % ( 24/44 ) of those with normal TSH ( P = 0.01 ) . Undetectable TSH at the end of treatment was the only independent variable in the logistic analysis to predict relapse . Treatment modality did not influence the relapse rate . This study has found that , in Spanish patients , the use of high doses of carbimazole with T4 offers no advantages in the treatment of GD hyperthyroidism Antithyroid drugs are commonly used as first-line treatment for Graves ' disease , but the optimum regimen for inducing remission remains unclear . We gave the block-replace regimen of carbimazole plus thyroxine to 100 patients for 6 or 12 months , to determine whether prolonged treatment is associated with fewer relapses . The remission rate one year after cessation of treatment was 59 % with the 6 month course and 65 % with 12 months ; this was not significantly different . We also analysed HLA markers identified by restriction fragment length polymorphisms and could not confirm the recently reported associations of outcome with HLA-DR4 or with an HLA-DQA2 allele . These results show that six months treatment with a block-replace regimen of antithyroid drugs is probably sufficient , in the Output:

Prescribing replacement thyroxine , either with the anti-thyroid drug treatment , or after this was completed , had no significant effect on relapse . Limited evidence suggested 12 - 18 months of anti-thyroid drug treatment should be used . The titration regimen appeared as effective as the Block-Replace regimen , and was associated with fewer adverse effects . However , relapse rates over 50 % and high participant drop-out rates in trials mean that the results should be interpreted with caution , and may suggest that other strategies for the management of Graves ' disease , such as radioiodine , should be considered more frequently as first-line therapy .

MS214179

***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 and Purpose Secondary prevention trials do not distinguish outcomes according to stroke cause . The purpose of the study was to determine whether trial efficacy of anticoagulation for secondary prevention could be replicated in clinical practice in strokes of different etiology . Methods A 2-year observation study was undertaken in 288 stroke patients with atrial fibrillation ( mean age 76 years ; 55 % women ) who were receiving anticoagulation therapy to maintain an international normalized ratio of 2.0 to 3.0 . Comparisons were made of ( 1 ) patient characteristics , anticoagulation control , and annual stroke/hemorrhage rates with those of the European Atrial Fibrillation Trial and ( 2 ) cause of recurrent stroke by initial stroke subtype . Results Subjects were 5 years older ( 95 % CI 3 to 7 years ) , and more patients had small-vessel stroke ( 26 % versus 14 % ; 95 % CI 3 % to 17 % ) compared with corresponding trial data . The duration spent in the target anticoagulation range ( 55 % versus 59 % ) , recurrent stroke rate ( 5.1 % versus 3.6 % per year ) , and major ( 2.3 % versus 2.2 % per year ) or minor ( 9.5 % versus 11.8 % per year ) hemorrhage rates were comparable with those in patients receiving warfarin in the r and omized study . Ten of 14 ( 71 % ) of embolic recurrences occurred in patients with a previous cardioembolic episode , and 8 of 11 ( 73 % ) lacunar recurrences occurred in patients with previous lacunar stroke as the qualifying event for anticoagulation ( P = 0.025 ) . Only 3 of 14 cardioembolic compared with 8 of 11 lacunar recurrences occurred during adequate anticoagulation . Conclusions Anticoagulation for secondary stroke prevention in clinical practice achieves outcomes comparable with those of r and omized trials . Nearly 26 % of qualifying strokes and 40 % of recurrences were nonembolic ; stroke subtype should be considered when making treatment decisions Abstract Background : This retrospective study was performed to develop a model to predict the maintenance dosage of the vitamin K antagonist acenocoumarol , based upon the first INR after a st and ard initial dosage regimen . Material and Methods : Out patients with atrial fibrillation ( n = 284 ) and initial regimens of 6 - 4 or 6 - 4 - 2 mg acenocoumarol on day 1 , 2 and 3 , respectively , were included . The maintenance dosage of the period 3–6 months after the instalment was related to the first INR after those st and ard initial dosage regimens , because in that period the INR was 76 % of the time within the therapeutic range and therefore considered suitable to perform the analysis . Results : A clear relation was found between the first INR , the maintenance dosage and the age . A model that predicts the maintenance dosage immediately after the st and ard initial dosage and based on the first INR and adjusted for age , has been developed , according to the formula : required dosage = 5.03 - 1.65 * ln ( first INR ) − 0.01 * age . Conclusion : We have developed a formula to predict the maintenance dosage of acenocoumarol . With this formula it is possible to install this maintenance dosage and thus achieve oral anticoagulant therapy within the therapeutic range at an earlier stage . This will have to be shown in a prospect i ve study Extremely elderly patients are being treated with anticoagulant therapy with increasing frequency . We sought to assess the rates of bleeding in such patients and to carefully examine risk factors that might predict this bleeding . This was a prospect i ve cohort study conducted from 1 January 2007 to 29 February 2008 at an anticoagulation clinic in Modena , Italy . Ninety patients , 90 years or older , among 1635 patients with nonvalvular atrial fibrillation were studied ; 69 ( 77 % ) were women with a median age of 91.71 years ( range 90–98 ) . During the enrolment period , all the patients were interviewed during an ambulatory visit and were followed in the outpatient setting . Hemorrhagic , thromboembolic and fatal events over 1 year of follow-up were monitored . Six ( 7 % ) patients discontinued vitamin K antagonists ( three due to bleeding , two due to noncompliance , two due to physician recommendation ) . Twenty-one ( 23 % ) patients died , and 35 ( 39 % ) were admitted to hospital . One patient had an intracranial hemorrhage [ 1 % , 95 % confidence interval ( CI ) 0.27–6.0 ] , two patients had a major extracranial hemorrhage ( 2 % , 95 % CI 0.7–8.0 ) . One patient had an ischemic stroke ( 1 % , 95 % CI 0.27–6.0 ) , two patients had embolic arterial ischemia ( 2 % , 95 % CI 0.7–8.0 ) . All the events occurred when the international normalized ratio was outside the target range , or after oral anticoagulation had been stopped . In our study of extremely elderly anticoagulated patients , we found low rates of bleeding and thromboembolism . These findings support the use of oral anticoagulants in such patients Background — Tecarfarin ( ATI-5923 ) is a novel oral vitamin K antagonist . Unlike warfarin , it is metabolized by esterases , escaping metabolism by the cytochrome P450 system and thereby avoiding cytochrome P450–mediated drug-drug or drug-food interactions as well as genetic variations found in the cytochrome P450 system . Both tecarfarin and warfarin can be monitored with the international normalized ratio . We hypothesized that the time in therapeutic range for tecarfarin will exceed values usually experienced with warfarin . Methods and Results — This was a 6- to 12-week open-label , multicenter , phase IIA study of 66 atrial fibrillation patients with a mild to moderate risk of stroke to determine the safety and tolerability of tecarfarin and to ascertain an optimal tecarfarin dosing regimen . Sixty-four subjects ( 97 % ) were taking warfarin at enrollment and were switched to tecarfarin . After the initial 3 weeks of tecarfarin treatment , the mean interpolated time in therapeutic range was 71.4 % . Only 10.9 % of patients had time in therapeutic range of < 45 % . Times in extreme international normalized ratio ranges of < 1.5 and > 4.0 were 1.2 % and 1.2 % , respectively . The median daily dose ( for an individual patient ) to maintain an international normalized ratio between 2 and 3 was 15.6 mg ( range , 6 to 29 mg ) . Conclusions — This is the first study of tecarfarin in patients with atrial fibrillation . It appears that tecarfarin may possess advantages over the currently available st and ard of care , warfarin , by improving time in therapeutic range . Adequately powered prospect i ve trials are warranted to definitively compare tecarfarin with warfarin in clinical setting s for which warfarin is indicated The purpose of this study was to establish the safety and efficacy of sodium warfarin in the secondary prophylaxis of venous thrombosis in patients with cancer . This was an inception cohort study of patients enrolled in an anticoagulation clinic between July 1991 and October 1996 . The rates of bleeding and recurrent thrombosis were evaluated in all the patients , and the results in patients with cancer ( n = 104 ) were compared with those without cancer ( n = 208 ) . The rate of major hemorrhage was 0.4 % and 0.3 % per treatment month in the patients with cancer and those without cancer , respectively . The rates of recurrent thrombosis were 1.2 % and 0.2 % per treatment month in the patients with cancer compared with those without cancer , respectively . We conclude that warfarin is safe when used for the secondary prophylaxis of patients with cancer who have had a venous or arterial thrombosis , and the risk of major hemorrhage is not significantly different when compared with the risk in patients without cancer . The rate of recurrent thrombosis is approximately sixfold higher in patients with cancer being treated with warfarin for secondary prophylaxis of thrombosis compared with patients without cancer . Nonetheless , the rate of recurrent thrombosis is not overly excessive , and warfarin can be viewed as a relatively effective form of therapy for these patients Background — Oral anticoagulation ( OAC ) therapy is effective in atrial fibrillation but requires vigilance to maintain the international normalized ratio in the therapeutic range . This report examines how differences in time in therapeutic range ( TTR ) between centers and between countries affect the outcomes of OAC therapy . Methods and Results — In a posthoc analysis , the TTRs of patients on OAC in a r and omized trial of OAC versus clopidogrel plus aspirin ( Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events [ ACTIVE W ] ) were used to calculate the mean TTR for each of 526 centers and 15 countries . Proportional-hazards analysis , with and without adjustment for baseline variables , was performed , with patients stratified by TTR quartile and country . A wide variation in TTRs was found between centers , with mean TTRs for centers in the 4 quartiles of 44 % , 60 % , 69 % , and 78 % . For patients at centers below the median TTR ( 65 % ) , no treatment benefit was demonstrated as measured by relative risk for vascular events of clopidogrel plus aspirin versus OAC ( relative risk , 0.93 ; 95 % confidence interval , 0.70 to 1.24 ; P=0.61 ) . However , for patients at centers with a TTR above the study median , OAC had a marked benefit , reducing vascular events by > 2-fold ( relative risk , 2.14 ; 95 % confidence interval , 1.61 to 2.85 ; P<0.0001 ) . Mean TTR also varied between countries from 46 % to 78 % ; relative risk ( clopidogrel plus aspirin versus OAC ) varied from 0.6 to 3.6 ( a 5-fold difference ) . A population -average model predicted that a TTR of 58 % would be needed to be confident that patients would benefit from being on OAC . Conclusions — A wide variation exists in international normalized ratio control , as measured by TTR , between clinical centers and between countries , which has a major impact on the treatment benefit of OAC therapy . For centers and countries , a target threshold TTR exists ( estimated between 58 % and 65 % ) below which there appears to be little benefit of OAC over antiplatelet therapy BACKGROUND Apixaban , an oral factor Xa inhibitor administered in fixed doses , may simplify the treatment of venous thromboembolism . METHODS In this r and omized , double-blind study , we compared apixaban ( at a dose of 10 mg twice daily for 7 days , followed by 5 mg twice daily for 6 months ) with conventional therapy ( subcutaneous enoxaparin , followed by warfarin ) in 5395 patients with acute venous thromboembolism . The primary efficacy outcome was recurrent symptomatic venous thromboembolism or death related to venous thromboembolism . The principal safety outcomes were major bleeding alone and major bleeding plus clinical ly relevant nonmajor bleeding . RESULTS The primary efficacy outcome occurred in 59 of 2609 patients ( 2.3 % ) in the apixaban group , as compared with 71 of 2635 ( 2.7 % ) in the conventional-therapy group ( relative risk , 0.84 ; 95 % confidence interval [ CI ] , 0.60 to 1.18 ; difference in risk [ apixaban minus conventional therapy ] , -0.4 percentage points ; 95 % CI , -1.3 to 0.4 ) . Apixaban was noninferior to conventional therapy ( P<0.001 ) for predefined upper limits of the 95 % confidence intervals for both relative risk ( < 1.80 ) and difference in risk ( < 3.5 percentage points ) . Major bleeding occurred in 0.6 % of patients who received apixaban and in 1.8 % of those who received conventional therapy ( relative risk , 0.31 ; 95 % CI , 0.17 to 0.55 ; P<0.001 for superiority ) . The composite outcome of major bleeding and clinical ly relevant nonmajor bleeding occurred in 4.3 % of the patients in the apixaban group , as compared with 9.7 % of those in the conventional-therapy group ( relative risk , 0.44 ; 95 % CI , 0.36 to 0.55 ; P<0.001 ) . Rates of other adverse events were similar in the two groups . CONCLUSIONS A fixed-dose regimen of apixaban alone was noninferior to conventional therapy for the treatment of acute venous thromboembolism and was associated with significantly less bleeding ( Funded by Pfizer and Bristol-Myers Squibb ; Clinical Trials.gov number , NCT00643201 ) CONTEXT When unfractionated heparin is used to treat acute venous thromboembolism , it is usually administered by intravenous infusion with coagulation monitoring , which requires hospitalization . However , subcutaneous administration of fixed-dose , weight-adjusted , unfractionated heparin may be suitable for inpatient and outpatient treatment Output:

A trend towards studies reporting greater numbers of VKA control measures over time was observed over our review time horizon , particularly , with AF and observational studies

MS214180

***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 AND PURPOSE Factor V Leiden and a prothrombin gene variant , G20210A , are mutations associated with a thrombotic risk . The aim of our study was to assess whether these mutations increase the risk of stroke in women under 45 years of age . METHODS We conducted a case-control study in western Washington state . Case patients were women aged 18 to 44 years with a first stroke ( n = 106 ) . Control subjects were women without stroke recruited from the same region by use of r and om-digit telephone dialing ( n = 391 ) . All were interviewed and provided blood specimens , which were genotyped for these mutations . RESULTS Factor V Leiden was found in 0.9 % of case patients , a single patient with a subarachnoid hemorrhage , and in 4.1 % of control subjects . The odds ratio ( OR ) for any stroke was 0.2 ( 95 % confidence interval [ CI ] , 0.03 to 1.7 ) . The prothrombin variant was found in 1.9 % of case patients , 1 with a venous stroke and 1 with an ischemic stroke , and in 1.6 % of control subjects . The OR for any stroke was 1.48 ( 95 % CI , 0.14 to 9.17 ) . ORs for stroke types were also not statistically significant . CONCLUSIONS In this study , neither factor V Leiden nor the prothrombin variant ( G20210A ) was an important risk factor for stroke in young women . In this setting , screening for these mutations can not be recommended . Unanswered by this study is whether screening would be useful in select patients , such as those with a strong family history of thrombophilia or those with venous strokes Background —The outcome of cardiac surgery is influenced by several factors , but the impact of specific genetic variants has not been systematic ally explored . Because blood conservation is a pressing issue in cardiac surgery , we tested the hypothesis that factor V Leiden ( FVL ) , a common coagulation factor polymorphism , may protect against blood loss and transfusion in patients undergoing cardiac surgery . Methods and Results —We enrolled 517 patients undergoing cardiac surgery , including 26 heterozygous FVL carriers , and evaluated the impact of FVL on chest tube output and transfusion by using univariate and multivariate techniques . For patients with FVL , blood loss at 6 ( 238±131 mL ) and 24 hours ( 522±302 mL ) was significantly lower than that for noncarriers ( 358±259 mL and 730±452 mL;P < 0.001 and P = 0.001 , respectively ) . In a multivariate regression analysis , controlling for ethnicity and factors known to affect blood loss , FVL was a significant independent contributor at both time points . Using a similar regression approach , FVL did not have a significant effect on the number of units transfused . However , logistic regression of the risk of receiving any transfusion during hospitalization demonstrated a significant independent protective effect of FVL on overall transfusion risk . Conclusions —FVL represents a common genetic trait that may protect against blood loss and transfusion in this population . This study demonstrates that genetic variability can affect the outcome of cardiac surgery Background and Purpose — Conflicting reports in the literature exist with regard to the association of apolipoprotein E ( apo E ) alleles and lobar intracerebral hemorrhage ( ICH ) . We genotyped 12 single-nucleotide polymorphisms in the 5′ upstream regulatory , exonic , and intronic regions of the apo E gene and performed genotype and haplotype association analyses . Methods — We prospect ively enrolled subjects with hemorrhagic stroke and matched them with 2 controls based on age , race , and sex . Each case was review ed by a physician to determine case status and location of the ICH . Multivariate logistic-regression modeling with backward elimination was used to determine significant risk factors for lobar ICH . Associations at the genotype and haplotype levels and linkage disequilibrium were conducted according to st and ard statistical methods . Results — Between May 1997 and December 2002 , 315 cases of ICH were recruited , of whom 107 were lobar ICH cases matched to 205 controls . No association was found for apo E2 , E3 , or E4 with nonlobar ICH . Independent , significant risk factors for lobar ICH included apo E4 , untreated hypertension , anticoagulant use , a first-degree relative with ICH , and ≤high school education ( compared with > high school education ) . Treated hypercholesterolemia compared with “ no history of hypercholesterolemia ” was associated with a decreased risk of lobar ICH . Haplotype association analysis demonstrated a significant association of the apo E gene with lobar ICH among whites ( P<0.0001 ) and blacks ( P=0.0024 ) . Conclusions — Apo E4 is independently associated with lobar ICH but not nonlobar ICH . Haplotypes of the apo E gene are associated with lobar ICH . Untreated hypertension is a risk factor for lobar ICH Intracerebral hemorrhage ( ICH ) is a common and serious type of stroke . Recent studies have shown that inherited factors that affect the devlopment of the vessel wall can increase the risk of ICH . We studied endoglin as a c and i date gene in patients with sporadic ICH , since mutations in this gene can cause telangiectasia formation . One hundred three patients with sporadic ICH and 202 controls were studied . The polymerase chain reaction and single‐str and conformational polymorphism analysis were used to screen for mutations in exon 7 of the endoglin gene . No coding mutations in exon 7 were identified in the ICH patients or controls . A 6‐base intronic insertion was found 26 bases beyond the 3′ end of exon 7 . The homozygous form of the insertion was present in 9 of 103 ( 8.7 % ) ICH patients compared with 4 of 202 ( 2.0 % ) controls , p = 0.012 ( odds ratio 4.8 [ 95 % confidence interval , 1.28 , 21.60 ] ) . Analysis of the endoglin transcript around the insertion did not reveal any changes in the RNA sequence . There were no obvious clinical features that distinguished the ICH patients with the homozygous insertion from the other patients . The pathophysiologic mechanism underlying this association remains to be determined The homozygous deletion allele of the angiotensin converting enzyme gene ( ACE/DD ) , homozygous threonine allele of the angiotensinogen gene ( AGN/TT ) , and the epsilon4 allele of the apolipoprotein E gene ( apoE/epsilon4 ) are reported to be associated with ischemic heart disease . Cerebrovascular disease ( CVD ) is another atherosclerotic disease ; and the effects of these polymorphisms on CVD have been confusing . In this study , we investigated whether ACE/DD , AGN/TT , and apoE/epsilon4 genotypes are associated with CVD and whether genetic risk is enhanced by the effect of one upon another . We ascertained these genotypes in patients with cerebral infa rct ion ( n = 55 ) and cerebral hemorrhage ( n = 38 ) , diagnosed by brain computed tomography . Control subjects for the infa rct ion group and the hemorrhage group were r and omly selected from 583 subjects matched for age , gender , and history of hypertension with patients . Frequency of ACE/DD genotype was higher in the patients with infa rct ion than in the controls ( chi2 = 6.1 , P < .05 ) . The AGN/TT genotype was not associated with either infa rct ion or hemorrhage , but it increased the relative risk for cerebral infa rct ion in the subjects with ACE/DD genotype ( chi2 = 8.0 , P < .01 , odds ratio ; 11.7 , 95 % confidence intervals : 1.4 to 96.0 ) . There was no significant association between apoE/epsilon4 and CVD . These results suggest that ACE/DD predicts cerebral infa rct ion , but not cerebral hemorrhage , and that AGN/TT enhances the risk for cerebral infa rct ion associated with ACE/DD To determine the prevalence of the factor V Leiden gene mutation in relation to the phenotypes of cerebral infa rct ion and cerebral hemorrhage , we studied 386 r and omly selected cases of acute stroke and 247 control subjects . Factor V genotype was determined by amplification of a 267-bp sequence of exon/intron 10 of the factor V gene . Levels of prothrombin fragment F(1 + 2 ) , a marker of thrombin generation , were determined in both acute and convalescent stroke and related to factor V genotype . Prothrombin fragment F(1 + 2 ) was assessed by using an enzyme-linked immunosorbent assay . Sixteen stroke cases ( 4.1 % ) were identified as having the mutation compared with 14 ( 5.6 % ) control subjects . Prothrombin fragment F(1 + 2 ) levels were estimated in 191 cases and found to be elevated both acutely and after 3 months , but they were not related to factor V genotype . Prothrombin fragment F(1 + 2 ) is elevated in acute stroke and requires further evaluation in relation to cerebrovascular disease . These results suggest that the factor V Leiden gene mutation is not a risk factor for arterial thrombosis causing stroke Abstract The ɛ4 allele of apolipoprotein E ( apoE ) is found more commonly among patients with Alzheimer ’s disease ( AD ) than in the normal population . ApoE is associated with brain amyloid , a component of cerebral amyloid angiopathy ( CAA ) , which is both a pathological feature of AD and a frequent cause of lobar intracerebral hemorrhage ( ICH ) . We hypothesized that the frequency of ɛ4 allele is higher in patients with CAA-related ICH than in hypertensive ICH and in the normal population . To test this hypothesis we compared the frequency of apoE alleles in four population s : 24 patients with lobar ICH , 24 matched patients with hypertensive ICH , 24 matched normal controls , and 173 population controls . Although there was a tendency to a higher frequency of apoE ɛ4 in lobar ICH patients , we found no significant differences in the frequency of this allele between the four studied population s. In addition we did not confirm the finding of some authors of a higher frequency of apoE ɛ2 in patients with lobar ICH than in the normal population . Previous studies on the subject are discussed . The relationship between apoE polymorphism and lobar CAA-related ICH remains to be clearly defined OBJECT The identification of polymorphisms associated with an increase in the risk of developing disease is integral to the development of genetic biomarkers to identify individuals at risk . Based on reports indicating a role for angiotensin-converting enzyme ( ACE ) in the pathogenesis of intracranial aneurysms ( IAs ) as well as hypertension , an independent risk factor for IAs , the authors investigated the association between an insertion/deletion ( I/D ) polymorphism in the ACE gene and IAs in a Caucasian population in the US . METHODS The patient population consisted of 162 r and omly selected Caucasian patients who underwent surgical repair of an IA at Memorial-Hermann Hospital ( Houston , TX ) and had no family history of the disease . The ACE I/D polymorphism was typed using polymerase chain reaction amplification of genomic DNA , and allele and genotype frequencies were compared between the patients with IAs and 143 healthy Caucasian volunteers ( control group ) by performing logistic regression and chi-square tests . The ACE I/D allele frequencies did not differ significantly between the patient and control population s. There were similar allele and genotype frequencies in male and female study participants in both patient and control population s. The authors found no evidence of an association between the allelic or genotypic distribution of the ACE I/D polymorphism and aneurysmal subarachnoid hemorrhage or unruptured IAs . CONCLUSIONS Contrary to findings in two European Caucasian population s ( one British and one Polish ) , this polymorphism did not contribute to the risk of developing IAs in a Caucasian population in the US Networks of investigators have begun sharing best practice s , tools and methods for analysis of associations between genetic variation and common diseases . A Network of Investigator Networks has been set up to drive the process , sponsored by the Human Genome Epidemiology Network . A workshop is planned to develop consensus guidelines for reporting results of genetic association studies . Published literature data bases will be integrated , and unpublished data , including ' negative ' studies , will be captured by online journals and through investigator networks . Systematic review s will be exp and ed to include more meta-analyses of individual-level data and prospect i ve meta-analyses . Field synopses will offer regularly up date d overviews The exact role of the fibrinolytic system in the pathogenesis of stroke remains to be established . Elevated circulating levels of plasminogen activator inhibitor-1 , the principle inactivator of the fibrinolytic system , have been related to the development of myocardial infa rct ion . There is evidence that a polymorphism in the promoter region of the PAI-1 gene is associated with circulating PAI-1 levels . We studied a common single nucleotide insertion/deletion ( 4G/5 G ) polymorphism by PCR in 558 patients with stroke , the pathological type of which was established by cranial computed tomography , and in 172 controls . 4G/5 G genotype and PAI-1 activity were investigated in relation to 1 ) stroke type and 2 ) mortality occurring within four weeks , three months and six Output:

Our data suggests a genetic contribution to some types of haemorrhagic stroke , with no overall responsible single gene but rather supporting a polygenic aetiology . Importantly , for several alleles previously found to be associated with protection from ischaemic stroke , there was a trend towards an increased risk of haemorrhagic stroke

MS214181

***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 Introduction The aim of the present study was to determine the effect of sitagliptin on microalbuminuria in patients with type 2 diabetes mellitus . Material s and Methods A total of 85 patients with type 2 diabetes mellitus ( age > 20 years , < 80 years , hemoglobin A1c [ HbA1c ] < 8.4 % ) were r and omized to patients taking sitagliptin 50 mg or other oral glucose‐lowering agents . The following parameters were evaluated at 0 , 3 and 6 months after the treatment : bodyweight , blood pressure , HbA1c , fasting plasma glucose , fasting plasma insulin , low‐density lipoprotein cholesterol , high‐density lipoprotein cholesterol , triglycerides , estimated glomerular filtration rate and urinary albumin excretion . The primary outcome was changes in urinary albumin excretion at 6 months . Results Significant and comparable falls in HbA1c and fasting plasma glucose were found in both groups . However , sitagliptin significantly reduced urinary albumin excretion within 6 months , especially in patients with high urinary albumin at baseline . A total of 27 patients with normoalbuminuria showed a reduction in urinary albumin excretion , suggesting that sitagliptin prevents the development of albuminuria . A total of 15 patients with albuminuria showed a reduction in urinary albumin excretion , suggesting the beneficial effect of sitagliptin in the early stage of diabetic nephropathy . There was a significant correlation between improvement of proteinuria and that of diastolic blood pressure . Conclusions The results suggested that sitagliptin improved albuminuria , in addition to improving glucose . The mechanism of the reduction of albuminuria by sitagliptin could be a direct effect , as well as an increase in active glucagon‐like peptide‐1 , independently affecting blood pressure , bodyweight and glucose metabolism . This trial was registered with the University Hospital Medical Information Network ( UMIN no. # 000010871 ) AIM To assess the safety and efficacy of the potent and selective dipeptidyl peptidase-4 inhibitor linagliptin 5 mg when given for 24 weeks to patients with type 2 diabetes who were either treatment-naive or who had received one oral antidiabetes drug ( OAD ) . METHODS This multicentre , r and omized , parallel group , phase III study compared linagliptin treatment ( 5 mg once daily , n = 336 ) with placebo ( n = 167 ) for 24 weeks in type 2 diabetes patients . Before r and omization , patients pretreated with one OAD underwent a washout period of 6 weeks , which included a placebo run-in period during the last 2 weeks . Patients previously untreated with an OAD underwent a 2-week placebo run-in period . The primary endpoint was the change in HbA1c from baseline after 24 weeks of treatment . RESULTS Linagliptin treatment result ed in a placebo-corrected change in HbA1c from baseline of -0.69 % ( p < 0.0001 ) at 24 weeks . In patients with baseline HbA1c ≥ 9.0 % , the adjusted reduction in HbA1c was 1.01 % ( p < 0.0001 ) . Patients treated with linagliptin were more likely to achieve a reduction in HbA1c of ≥0.5 % at 24 weeks than those in the placebo arm ( 47.1 and 19.0 % , respectively ; odds ratio , OR = 4.2 , p < 0.0001 ) . Fasting plasma glucose improved by -1.3 mmol/l ( p < 0.0001 ) with linagliptin vs. placebo , and linagliptin produced an adjusted mean reduction from baseline after 24 weeks in 2-h postpr and ial glucose of -3.2 mmol/l ( p < 0.0001 ) . Statistically significant and relevant treatment differences were observed for proinsulin/insulin ratio ( p = 0.025 ) , Homeostasis Model Assessment -%B ( p = 0.049 ) and disposition index ( p = 0.0005 ) . There was no excess of hypoglycaemic episodes with linagliptin vs. placebo and no patient required third-party intervention . Mild or moderate renal impairment did not influence the trough plasma levels of linagliptin . CONCLUSIONS Monotherapy with linagliptin produced a significant , clinical ly meaningful and sustained improvement in glycaemic control , accompanied by enhanced parameters of β-cell function . The safety profile of linagliptin was comparable with that of placebo BACKGROUND The cardiovascular safety and efficacy of many current antihyperglycemic agents , including saxagliptin , a dipeptidyl peptidase 4 ( DPP-4 ) inhibitor , are unclear . METHODS We r and omly assigned 16,492 patients with type 2 diabetes who had a history of , or were at risk for , cardiovascular events to receive saxagliptin or placebo and followed them for a median of 2.1 years . Physicians were permitted to adjust other medications , including antihyperglycemic agents . The primary end point was a composite of cardiovascular death , myocardial infa rct ion , or ischemic stroke . RESULTS A primary end-point event occurred in 613 patients in the saxagliptin group and in 609 patients in the placebo group ( 7.3 % and 7.2 % , respectively , according to 2-year Kaplan-Meier estimates ; hazard ratio with saxagliptin , 1.00 ; 95 % confidence interval [ CI ] , 0.89 to 1.12 ; P=0.99 for superiority ; P<0.001 for noninferiority ) ; the results were similar in the " on-treatment " analysis ( hazard ratio , 1.03 ; 95 % CI , 0.91 to 1.17 ) . The major secondary end point of a composite of cardiovascular death , myocardial infa rct ion , stroke , hospitalization for unstable angina , coronary revascularization , or heart failure occurred in 1059 patients in the saxagliptin group and in 1034 patients in the placebo group ( 12.8 % and 12.4 % , respectively , according to 2-year Kaplan-Meier estimates ; hazard ratio , 1.02 ; 95 % CI , 0.94 to 1.11 ; P=0.66 ) . More patients in the saxagliptin group than in the placebo group were hospitalized for heart failure ( 3.5 % vs. 2.8 % ; hazard ratio , 1.27 ; 95 % CI , 1.07 to 1.51 ; P=0.007 ) . Rates of adjudicated cases of acute and chronic pancreatitis were similar in the two groups ( acute pancreatitis , 0.3 % in the saxagliptin group and 0.2 % in the placebo group ; chronic pancreatitis , < 0.1 % and 0.1 % in the two groups , respectively ) . CONCLUSIONS DPP-4 inhibition with saxagliptin did not increase or decrease the rate of ischemic events , though the rate of hospitalization for heart failure was increased . Although saxagliptin improves glycemic control , other approaches are necessary to reduce cardiovascular risk in patients with diabetes . ( Funded by AstraZeneca and Bristol-Myers Squibb ; SAVOR-TIMI 53 Clinical Trials.gov number , NCT01107886 . ) Results of the main Action to Control Cardiovascular Risk in Diabetes ( ACCORD ) trial indicate that intensive glucose lowering increases cardiovascular and all-cause mortality . As the contribution of mild-to-moderate chronic kidney disease ( CKD ) to these risks is not known , we assessed the impact on cardiovascular outcomes in this population . Renal function data were available on 10,136 patients of the original ACCORD cohort . Of those , 6,506 were free of CKD at baseline and 3,636 met the criteria for CKD . Participants were r and omly assigned to a treatment strategy of either intensive or st and ard glycemic goal . The primary outcome , all-cause and cardiovascular mortality , and prespecified secondary outcomes were evaluated . Risk for the primary outcome was 87 % higher in patients with than in those without CKD ( hazard ratio of 1.866 ; 95 % CI : 1.651 - 2.110 ) . All prespecified secondary outcomes were 1.5 to 3 times more frequent in patients with than in those without CKD . In patients with CKD , compared with st and ard therapy , intensive glucose lowering was significantly associated with both 31 % higher all-cause mortality ( 1.306 : 1.065 - 1.600 ) and 41 % higher cardiovascular mortality ( 1.412 : 1.052 - 1.892 ) . No significant effects were found in patients without CKD . Thus , in high-risk patients with type II diabetes , mild and moderate CKD is associated with increased cardiovascular risk . Intensive glycemic control significantly increases the risk of cardiovascular and all-cause mortality in this population OBJECTIVE To evaluate the efficacy and long-term safety of linagliptin added to basal insulins in type 2 diabetes inadequately controlled on basal insulin with or without oral agents . RESEARCH DESIGN AND METHODS A total of 1,261 patients ( HbA1c ≥7.0 % [ 53 mmol/mol ] to ≤10.0 % [ 86 mmol/mol ] ) on basal insulin alone or combined with metformin and /or pioglitazone were r and omized ( 1:1 ) to double-blind treatment with linagliptin 5 mg once daily or placebo for ≥52 weeks . The basal insulin dose was kept unchanged for 24 weeks but could thereafter be titrated according to fasting plasma glucose levels at the investigators ’ discretion . The primary end point was the mean change in HbA1c from baseline to week 24 . The safety analysis incorporated data up to a maximum of 110 weeks . RESULTS At week 24 , HbA1c changed from a baseline of 8.3 % ( 67 mmol/mol ) by −0.6 % ( −6.6 mmol/mol ) and by 0.1 % ( 1.1 mmol/mol ) with linagliptin and placebo , respectively ( treatment difference −0.65 % [ 95 % CI −0.74 to −0.55 ] [ −7.1 mmol/mol ] ; P < 0.0001 ) . Despite the option to uptitrate basal insulin , it was adjusted only slightly upward ( week 52 , linagliptin 2.6 IU/day , placebo 4.2 IU/day ; P < 0.003 ) , result ing in no further HbA1c improvements . Frequencies of hypoglycemia ( week 24 , linagliptin 22.0 % , placebo 23.2 % ; treatment end , linagliptin 31.4 % , placebo 32.9 % ) and adverse events ( linagliptin 78.4 % , placebo 81.4 % ) were similar between groups . Mean body weight remained unchanged ( week 52 , linagliptin −0.30 kg , placebo −0.04 kg ) . CONCLUSIONS Linagliptin added to basal insulin therapy significantly improved glycemic control relative to placebo without increasing hypoglycemia or body weight OBJECTIVE To compare the efficacy and safety of weekly albiglutide with daily sitagliptin , daily glimepiride , and placebo . Research Design And Methods Patients with type 2 diabetes receiving metformin were r and omized to albiglutide ( 30 mg ) , sitagliptin ( 100 mg ) , glimepiride ( 2 mg ) , or placebo . Blinded dose titration for albiglutide ( to 50 mg ) and glimepiride ( to 4 mg ) was based on predefined hyperglycemia criteria . The primary end point was change in HbA1c from baseline at week 104 . Secondary end points included fasting plasma glucose ( FPG ) , weight , and time to hyperglycemic rescue . RESULTS Baseline characteristics were similar among the albiglutide ( n = 302 ) , glimepiride ( n = 307 ) , sitagliptin ( n = 302 ) , and placebo ( n = 101 ) groups . Baseline HbA1c was 8.1 % ( 65.0 mmol/mol ) ; mean age was 54.5 years . The mean doses for albiglutide and glimepiride at week 104 were 40.5 and 3.1 mg , respectively . At week 104 , albiglutide significantly reduced HbA1c compared with placebo ( −0.9 % [ −9.8 mmol/mol ] ; P < 0.0001 ) , sitagliptin ( −0.4 % [ −4.4 mmol/mol ] ; P = 0.0001 ) , and glimepiride ( −0.3 % [ −3.3 mmol/mol ] ; P = 0.0 Output:

Conclusions : Dipeptidyl peptidase-4 inhibitors in patients with chronic kidney disease caused a modest reduction in hemoglobin A1c versus placebo , but not when compared with sulfonylureas or albiglutide , or when used in patients on dialysis . Additional active-comparator studies are needed to further eluci date the role of dipeptidyl peptidase-4 inhibitors in patients with chronic kidney disease stages 3–5 or on dialysis

MS214182

***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 possible benefit for patients from follow‐up examinations after curative surgery for colorectal cancer is unproven . The purpose of this study was to determine whether survival is improved by frequent follow‐up examinations Objective To assess whether colon cancer follow-up can be organised by general practitioners ( GPs ) without a decline in the patient 's quality of life ( QoL ) and increase in cost or time to cancer diagnoses , compared to hospital follow-up . Design R and omised controlled trial . Setting Northern Norway Health Authority Trust , 4 trusts , 11 hospitals and 88 local communities . Participants Patients surgically treated for colon cancer , hospital surgeons and community GPs . Intervention 24-month follow-up according to national guidelines at the community GP office . To ensure a high follow-up guideline adherence , a decision support tool for patients and GPs were used . Main outcome measures Primary outcomes were QoL , measured by the global health scales of the European Organisation for Research and Treatment of Cancer QoL Question naire ( EORTC QLQ C-30 ) and EuroQol-5D ( EQ-5D ) . Secondary outcomes were cost-effectiveness and time to cancer diagnoses . Results 110 patients were r and omised to intervention ( n=55 ) or control ( n=55 ) , and followed by 78 GPs ( 942 follow-up months ) and 70 surgeons ( 942 follow-up months ) , respectively . Compared to baseline , there was a significant improvement in postoperative QoL ( p=0.003 ) , but no differences between groups were revealed ( mean difference at 1 , 3 , 6 , 9 , 12 , 15 , 18 , 21 and 24-month follow-up appointments ) : Global Health ; Δ−2.23 , p=0.20 ; EQ-5D index ; Δ−0.10 , p=0.48 , EQ-5D VAS ; Δ−1.1 , p=0.44 . There were no differences in time to recurrent cancer diagnosis ( GP 35 days vs surgeon 45 days , p=0.46 ) ; 14 recurrences were detected ( GP 6 vs surgeon 8) and 7 metastases surgeries performed ( GP 3 vs surgeon 4 ) . The follow-up programme initiated 1186 healthcare contacts ( GP 678 vs surgeon 508 ) , 1105 diagnostic tests ( GP 592 vs surgeon 513 ) and 778 hospital travels ( GP 250 vs surgeon 528 ) . GP organised follow-up was associated with societal cost savings ( £ 8233 vs £ 9889 , p<0.001 ) . Conclusions GP-organised follow-up was associated with no decline in QoL , no increase in time to recurrent cancer diagnosis and cost savings . Trial registration Clinical Trials.gov identifier NCT00572143 BACKGROUND Although colonoscopy plays an important role in postoperative surveillance of patients with colorectal cancer , the optimum protocol for colonoscopic surveillance has not been established . OBJECTIVE Our purpose was to compare the efficacy of 2 different colonoscopic surveillance strategies in terms of both survival and recurrence resectability . DESIGN Prospect i ve , r and omized , controlled trial . SETTING A teaching hospital in Sun Yat-sen University . PATIENTS Three hundred twenty-six consecutive patients undergoing radical surgery for colorectal cancer . INTERVENTION In the intensive colonoscopic surveillance group ( ICS group , n = 165 ) , colonoscopy was performed at 3-month intervals for 1 year , at 6-month intervals for the next 2 years , and once a year thereafter . In the routine colonoscopic surveillance group ( RCS group , n = 161 ) , colonoscopy was performed at 6 months , 30 months , and 60 months postoperatively . MAIN OUTCOME MEASUREMENTS AND RESULTS The 5-year survival rate was 77 % in the ICS group and 73 % in the RCS group ( P > .05 ) . Postoperative colorectal cancer was detected in 13 patients ( 8.1 % ) in the ICS group and in 18 patients ( 11.4 % ) in the RCS group . In the ICS group , there were more asymptomatic postoperative colorectal cancers ( P = .04 ) , more patients had reoperation with curative intent ( P = .048 ) , and the probability of survival after postoperative colorectal cancer was higher ( P = .03 ) . LIMITATION Lack of detailed characterization of metachronous colorectal adenomas in these patients . CONCLUSIONS Although the patients in the ICS group had more curative operations for postoperative colorectal cancer and survived significantly longer , ICS itself did not improve overall survival OBJECTIVE To determine whether an intensified follow-up of patients with colorectal cancer can lead to improved reresectability and a better long-term survival . DESIGN A prospect i ve r and omized trial of 106 patients . SETTING Oulu University Hospital , a referral center in northern Finl and . PATIENTS A total of 106 consecutive patients who underwent radical resection for colorectal cancer , 54 of whom were r and omized into a conventional follow-up group and 52 into an intensified follow-up group . MAIN OUTCOME MEASURES After a 5-year follow-up , the time of detection of recurrence , the recurrence rates , the first method showing recurrence , the mode of recurrence , reresectability , and survival were compared between the groups . RESULTS The recurrences were identified earlier in the intensified follow-up group than in the conventional follow-up group ( mean + /- SD , 10 + /- 5 months vs 15 + /- 10 months ) . The overall recurrence rate was 41 % , with 39 % in the conventional group and 42 % in the intensified group . Carcinoembryonic antigen determination was the most common method showing recurrence in both groups . Endoscopy and ultrasound were beneficial in the intensified follow-up group , but computed tomography failed to improve the diagnostics . The mode of recurrence did not differ between the groups . Radical resections were performed on 19 % ( 8/43 ) of the patients , 14 % ( 3/21 ) in the conventional group and 22 % ( 5/22 ) in the intensified group . The cumulative 5-year survival was 54 % in the conventional group and 59 % in the intensified group . CONCLUSION Earlier detection of recurrent colorectal cancer by intensified follow-up does not lead to either significantly increased reresectability or improved 5-year survival Introduction The COLOFOL trial , a prospect i ve r and omized multicenter trial comparing two follow-up regimes after curative surgical treatment for colorectal cancer , focuses on detection of asymptomatic recurrences . This paper aims to describe the design and recruitment procedure in the COLOFOL trial , comparing demographic characteristics between r and omized patients and eligible patients not included in the study . Material s and methods COLOFOL was design ed as a pragmatic trial with wide inclusion criteria and few exclusion criteria , in order to obtain a sample reflecting the general patient population . To be eligible , patients had to be 75 years or younger and curatively resected for stage II or III colorectal cancer . Exclusion criteria were hereditary colorectal cancer , no signed consent , other malignancy , and life expectancy less than 2 years due to concomitant disease . In four of the 24 participating centers , we scrutinized hospital inpatient data to identify all colorectal cancer patients who underwent surgery , in order to ascertain all eligible patients who were not included in the study and to compare them with enrolled patients . Results Of a total of 4,445 eligible patients , 2,509 patients were r and omized ( 56.4 % inclusion rate ) . A total of 1,221 eligible patients were identified in the scrutinized hospitals , of which 684 ( 56 % ) were r and omized . No difference in age or sex distribution was observed between r and omized and nonr and omized eligible patients . However , a difference was noted in tumor location and stage distribution , with 5.6 % more patients in the r and omized group having colon cancer and 6.7 % more patients having stage II disease . Conclusion Patients in the two study arms were not only demographically similar , but also similar to nonincluded eligible patients , apart from stage and localization . The analyses will be stratified by these variables . Taken together , we conclude that our trial results will be robust and possible to extrapolate to the target population IMPORTANCE Intensive follow-up after surgery for colorectal cancer is common practice but is based on limited evidence . OBJECTIVE To assess the effect of scheduled blood measurement of carcinoembryonic antigen ( CEA ) and computed tomography ( CT ) as follow-up to detect recurrent colorectal cancer treatable with curative intent . DESIGN , SETTING , AND PARTICIPANTS R and omized clinical trial in 39 National Health Service hospitals in the United Kingdom ; 1202 eligible participants were recruited between January 2003 and August 2009 who had undergone curative surgery for primary colorectal cancer , including adjuvant treatment if indicated , with no evidence of residual disease on investigation . INTERVENTIONS Participants were r and omly assigned to 1 of 4 groups : CEA only ( n = 300 ) , CT only ( n = 299 ) , CEA+CT ( n = 302 ) , or minimum follow-up ( n = 301 ) . Blood CEA was measured every 3 months for 2 years , then every 6 months for 3 years ; CT scans of the chest , abdomen , and pelvis were performed every 6 months for 2 years , then annually for 3 years ; and the minimum follow-up group received follow-up if symptoms occurred . MAIN OUTCOMES AND MEASURES The primary outcome was surgical treatment of recurrence with curative intent ; secondary outcomes were mortality ( total and colorectal cancer ) , time to detection of recurrence , and survival after treatment of recurrence with curative intent . RESULTS After a mean 4.4 ( SD , 0.8 ) years of observation , cancer recurrence was detected in 199 participants ( 16.6 % ; 95 % CI , 14.5%-18.7 % ) overall ; 71 of 1202 participants ( 5.9 % ; 95 % CI , 4.6%-7.2 % ) were treated for recurrence with curative intent , with little difference according to Dukes staging ( stage A , 5.1 % [ 13/254 ] ; stage B , 6.1 % [ 34/553 ] ; stage C , 6.2 % [ 22/354 ] ) . Surgical treatment of recurrence with curative intent was 2.3 % ( 7/301 ) in the minimum follow-up group , 6.7 % ( 20/300 ) in the CEA group , 8 % ( 24/299 ) in the CT group , and 6.6 % ( 20/302 ) in the CEA+CT group . Compared with minimum follow-up , the absolute difference in the percentage of patients treated with curative intent in the CEA group was 4.4 % ( 95 % CI , 1.0%-7.9 % ; adjusted odds ratio [ OR ] , 3.00 ; 95 % CI , 1.23 - 7.33 ) , in the CT group was 5.7 % ( 95 % CI , 2.2%-9.5 % ; adjusted OR , 3.63 ; 95 % CI , 1.51 - 8.69 ) , and in the CEA+CT group was 4.3 % ( 95 % CI , 1.0%-7.9 % ; adjusted OR , 3.10 ; 95 % CI , 1.10 - 8.71 ) . The number of deaths was not significantly different in the combined intensive monitoring groups ( CEA , CT , and CEA+CT ; 18.2 % [ 164/901 ] ) vs the minimum follow-up group ( 15.9 % [ 48/301 ] ; difference , 2.3 % ; 95 % CI , -2.6 % to 7.1 % ) . CONCLUSIONS AND RELEVANCE Among patients who had undergone curative surgery for primary colorectal cancer , intensive imaging or CEA screening each provided an increased rate of surgical treatment of recurrence with curative intent compared with minimal follow-up ; there was no advantage in combining CEA and CT . If there is a survival advantage to any strategy , it is likely to be small . TRIAL REGISTRATION is rct n.org Identifier : 41458548 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 PURPOSE Although systematic postoperative surveillance of patients with colorectal cancer has been demonstrated to improve survival , it remains unknown whether a more intensive strategy provides any significant advantage . This prospect i ve , multicenter , r and omized , controlled trial was aim ed at comparing the efficacy of two different surveillance strategies in terms of both survival and recurrence resectability . PATIENTS AND METHODS Patients with stage II or III colorectal cancer were allocated r and omly to either a simple surveillance strategy including clinical evaluation and serum carcinoembryonic antigen monitoring , or an intensive strategy in which abdominal computed tomography or ultrasonography , chest radiograph , and colonoscopy were added . RESULTS A total Output:

Based on pooled data from r and omized trials published from 1995 to 2016 , the anticipated survival benefit from surgical treatment result ing from earlier detection of metastases has not been achieved

MS214183

***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 Effective internet-based programs for depression usually incorporate a component that provides telephone or email contact . Open access websites , without such contact , show high rates of attrition and poorer outcomes . The present study was design ed as an exploratory investigation of the parameters that influence the effectiveness and retention of users on open access websites . We investigated whether brief cognitive behaviour therapy ( CBT ) was as effective as an extended version , whether add-on components of behaviour therapy or stress management contributed to positive outcomes , and whether longer programs were associated with greater attrition . METHOD An online r and omized controlled trial ( RCT ) was conducted between 13 January 2005 and 26 May 2005 ( 19 weeks ) . A total of 2794 registrants ( 1846 women and 948 men ; median age category 35 - 44 years ) with elevated scores on the Goldberg Depression Scale of 5.96 ( S.D.=2.09 ) elected online to be r and omized to one of six versions of a CBT website . The versions were compiled consisting of various components of brief CBT , extended CBT , behaviour strategies , stress management and problem solving . RESULTS A total of 20.4 % of participants completed the assigned intervention . The interaction of measurement occasion and treatment version was significant [ F(13,131)=2.20 , p=0.01 ] . A single module of brief introductory CBT was not effective in reducing depression symptoms . However , extended CBT with or without the addition of behaviour strategies result ed in the reduction of depression . CONCLUSIONS Brief CBT-based interventions are not as effective as extended interventions . However , longer programs are associated with higher rates of dropout Current approaches to the treatment of panic disorder ( PD ) include a treatment package consisting of relaxation training ( RT ) , cognitive therapy ( CT ) , and exposure-based components . In an examination of the separate effects of RT and CT without formally taught exposure of any form , 64 PD patients were assigned r and omly to one of these treatment protocol s or to a minimal-contact control ( MCC ) condition . Both RT and CT were superior to the MCC condition on a variety of measures pertaining to panic , global psychological functioning , agoraphobic fear , and other associated fears . A significantly greater percentage of patients were classified as treatment responders ( based on a composite index ) after CT ( 82 % ) and RT ( 68 % ) , compared with the control group ( 36 % ) . On measures of agoraphobic fear , CT patients fared slightly better than RT patients . Some support was demonstrated for specific cognitive changes after CT , although treatment specificity was not strongly supported overall . These results are discussed in light of current theories of PD and the presumed importance of exposure in its treatment Mild depressive syndromes are highly prevalent among primary -care patients . Evidence -based treatment recommendations need to be derived directly from this diagnostically heterogeneous group . The primary aim was to assess the efficacy of sertraline and cognitive-behavioural group therapy for treatment of depressed primary -care patients , the secondary aim was to evaluate if receiving treatment according to free choice is associated with a better outcome than r and omization to a particular treatment . We conducted a r and omized , placebo-controlled , single-centre , 10-wk trial with five arms : sertraline ( flexible dosages up to 200 mg/d ) ( n = 83 ) ; placebo ( n = 83 ) ; manual-guided cognitive-behavioural group therapy ( one individual session and nine group sessions per 90 min ) ( n = 61 ) ; guided self-help group ( control condition , n = 59 ) ; and treatment with sertraline or cognitive-behavioural group therapy according to patients ' choice ( n = 82 ) . From 1099 consecutively screened adult patients , 368 formed the intent-to-treat population with milder forms of depression . Primary outcome was a global efficacy measure combining z-converted Hamilton Depression Rating Scale and clinician-rated Inventory for Depressive Symptomatology scores . Sertraline was superior to placebo ( p = 0.03 ) . Outcome for guided self-help groups was worse compared to cognitive-behavioural group therapy ( p = 0.002 ) and compared to all other treatment arms including pill placebo ( secondary analyses ) . Outcome in the patients ' choice arm was similar to that in the sertraline and cognitive-behavioural group therapy . Overall , sertraline is efficacious in primary -care patients with milder forms of depression . The superiority of cognitive-behavioural group therapy over guided self-help groups might partly be explained by ' nocebo ' effects of the latter 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 BACKGROUND Major depression can be treated by means of cognitive-behavioural therapy , but as skilled therapists are in short supply there is a need for self-help approaches . Many individuals with depression use the internet for discussion of symptoms and to share their experience . AIMS To investigate the effects of an internet-administered self-help programme including participation in a monitored , web-based discussion group , compared with participation in web-based discussion group only . METHOD A r and omised controlled trial was conducted to compare the effects of internet-based cognitive-behavioural therapy with minimal therapist contact ( plus participation in a discussion group ) with the effects of participation in a discussion group only . RESULTS Internet-based therapy with minimal therapist contact , combined with activity in a discussion group , result ed in greater reductions of depressive symptoms compared with activity in a discussion group only ( waiting-list control group ) . At 6 months ' follow-up , improvement was maintained to a large extent . CONCLUSIONS Internet-delivered cognitive cognitive-behavioural therapy should be pursued further as a complement or treatment alternative for mild-to-moderate depression Background Guided self-help programs for depression ( with associated therapist contact ) have been successfully delivered over the Internet . However , previous trials of pure self-help Internet programs for depression ( without therapist contact ) , including an earlier trial conducted by us , have failed to yield positive results . We hypothesized that methods to increase participant usage of the intervention , such as postcard or telephone reminders , might result in significant effects on depression . Objectives This paper presents a second r and omized trial of a pure self-help Internet site , ODIN ( Overcoming Depression on the InterNet ) , for adults with self-reported depression . We hypothesized that frequently reminded participants receiving the Internet program would report greater reduction in depression symptoms and greater improvements in mental and physical health functioning than a comparison group with usual treatment and no access to ODIN . Methods This was a three-arm r and omized control trial with a usual treatment control group and two ODIN intervention groups receiving reminders through postcards or brief telephone calls . The setting was a nonprofit health maintenance organization ( HMO ) . We mailed recruitment brochures by US post to two groups : adults ( n = 6030 ) who received depression medication or psychotherapy in the previous 30 days , and an age- and gender-matched group of adults ( n = 6021 ) who did not receive such services . At enrollment and at 5- , 10- and 16-weeks follow-up , participants were reminded by email ( and telephone , if nonresponsive ) to complete online versions of the Center for Epidemiological Studies Depression Scale ( CES-D ) and the Short Form 12 ( SF-12 ) . We also recorded participant HMO health care services utilization in the 12 months following study enrollment . Results Out of a recruitment pool of 12051 approached subjects , 255 persons accessed the Internet enrollment site , completed the online consent form , and were r and omized to one of the three groups : ( 1 ) treatment as usual control group without access to the ODIN website ( n = 100 ) , ( 2 ) ODIN program group with postcard reminders ( n = 75 ) , and ( 3 ) ODIN program group with telephone reminders ( n = 80 ) . Across all groups , follow-up completion rates were 64 % ( n = 164 ) at 5 weeks , 68 % ( n = 173 ) at 10 weeks , and 66 % ( n = 169 ) at 16 weeks . In an intention-to-treat analysis , intervention participants reported greater reductions in depression compared to the control group ( P = .03 ; effect size = 0.277 st and ard deviation units ) . A more pronounced effect was detected among participants who were more severely depressed at baseline ( P = .02 ; effect size = 0.537 st and ard deviation units ) . By the end of the study , 20 % more intervention participants moved from the disordered to normal range on the CES-D. We found no difference between the two intervention groups with different reminders in outcomes measures or in frequency of log-ons . We also found no significant intervention effects on the SF-12 or health care services . Conclusions In contrast to our earlier trial , in which participants were not reminded to use ODIN , in this trial we found a positive effect of the ODIN intervention compared to the control group . Future studies should address limitations of this trial , including relatively low enrollment and follow-up completion rates , and a restricted number of outcome measures . However , the low incremental costs of delivering this Internet program makes it feasible to offer this type of program to large population s with widespread Internet access Background Self-help therapies are often effective in reducing mental health problems . We developed a new Web-based self-help intervention based on problem-solving therapy , which may be used for people with different types of comorbid problems : depression , anxiety , and work-related stress . Objective The aim was to study whether a Web-based self-help intervention is effective in reducing depression , anxiety , and work-related stress ( burnout ) . Methods A total of 213 participants were recruited through mass media and r and omized to the intervention ( n = 107 ) or a waiting list control group ( n = 106 ) . The Web-based course took 4 weeks . Every week an automated email was sent to the participants to explain the contents and exercises for the coming week . In addition , participants were supported by trained psychology students who offered feedback by email on the completed exercises . The core element of the intervention is a procedure in which the participants learn to approach solvable problems in a structured way . At pre-test and post-test , we measured the following primary outcomes : depression ( CES-D and MDI ) , anxiety ( SCL-A and HADS ) , and work-related stress ( MBI ) . Quality of life ( EQ-5D ) was measured as a secondary outcome . Intention-to-treat analyses were performed . Results Of the 213 participants , 177 ( 83.1 % ) completed the baseline and follow-up question naires ; missing data were statistically imputed . Of all 107 participants in the intervention group , 9 % ( n = 10 ) dropped out before the course started and 55 % ( n = 59 ) completed the whole course . Among all participants , the intervention was effective in reducing symptoms of depression ( CES-D : Cohen ’s d = 0.50 , 95 % confidence interval ( CI ) 0.22 - 0.79 ; MDI : d = 0.33 , 95 % CI 0.03 - 0.63 ) and anxiety ( SCL-A : d = 0.42 , 95 % CI 0.14 - 0.70 ; HADS : d = 0.33 , 95 % CI 0.04 - 0.61 ) as well as in enhancing quality of life ( d = 0.31 , 95 % CI 0.03 - 0.60 ) . Moreover , a higher percentage of patients in the intervention group experienced a significant improvement in symptoms ( CES-D : odds ratio [ OR ] = 3.5 , 95 % CI 1.9 - 6.7 ; MDI : OR = 3.7 , 95 % CI 1.4 - 10.0 ; SCL-A : OR = 2.1 , 95 % CI 1.0 - 4.6 ; HADS : OR = 3.1 , 95 % CI 1.6 - 6.0 ) . Patients in the intervention group also recovered more often ( MDI : OR = 2.2 ; SCL-A : OR = 2.0 ; HADS < 8) , although these results were not statistically significant . The course was less effective for work-related stress , but participants in the intervention group recovered more often from burnout than those in the control group ( OR = 4.0 , 95 % CI 1.2 - 13.5 ) . Conclusions We demonstrated statistically and clinical ly significant effects on symptoms of depression and anxiety . These effects were even more pronounced among participants with more severe baseline problems and for participants who fully completed the course . The effects on work-related stress and quality of life were less clear . To our knowledge , this is the first trial of a Web-based , problem-solving intervention Output:

BACKGROUND Cognitive-behavioural therapy (CBT)-based guided self-help ( GSH ) has been suggested to be an effective intervention for mild to moderate anxiety and depression , yet the evidence seems inconclusive , with some studies reporting that GSH is effective and others finding that GSH is ineffective . Meta- analysis indicated the effectiveness of GSH at post-treatment , although GSH was found to have limited effectiveness at follow-up or among more clinical ly representative sample s. Studies that reported greater effectiveness of GSH tended to be of lower method ological quality and generally involved participants who were self-selected rather than recruited through clinical referrals . Further rigorous evidence based on clinical population s that examines longer-term outcomes is required before CBT-based GSH interventions can be deemed effective for adults accessing primary care services for treatment of anxiety and depression

MS214184

***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: D iabetes is one of the most costly and burdensome chronic diseases of our time and is a condition that is increasing in epidemic proportions in the U.S. and throughout the world ( 1 ) . The complications result ing from the disease are a significant cause of morbidity and mortality and are associated with the damage or failure of various organs such as the eyes , kidneys , and nerves . Individuals with type 2 diabetes are also at a significantly higher risk for coronary heart disease , peripheral vascular disease , and stroke , and they have a greater likelihood of having hypertension , dyslipidemia , and obesity ( 2–6 ) . There is also growing evidence that at glucose levels above normal but below the diabetes threshold diagnostic now referred to as pre-diabetes , there is a substantially increased risk of cardiovascular disease ( CVD ) and death ( 5,7–10 ) . In these individuals , CVD risk factors are also more prevalent ( 5–7,9,11–14 ) , which further increases the risk but is not sufficient to totally explain it . In contrast to the clear benefit of glucose lowering to prevent or retard the progression of microvascular complications associated with diabetes ( 15– 18,21 ) , it is less clear whether the high rate of CVD in people with impaired glucose homeostasis , i.e. , those with impaired fasting glucose ( IFG ) , impaired glucose tolerance ( IGT ) , or diabetes , is caused by elevated blood glucose levels or will respond to treatments that lower blood glucose . Epidemiological studies have shown a clear relationship ( 19,20 ) , whereas intervention trials in people with diabetes suggest , but have not demonstrated , a clear benefit of glycemic control ( 15,16,21,22 ) . Additionally , there are no studies that have investigated a benefit of glucose lowering on macrovascular disease in subjects with only pre-diabetes ( IFG or IGT ) but not diabetes . Although the treatment of diabetes has become increasingly sophisticated , with over a dozen pharmacological agents available to lower blood glucose , a multitude of ancillary supplies and equipment available , and a clear recognition by health care professionals and patients that diabetes is a serious disease , the normalization of blood glucose for any appreciable period of time is seldom achieved ( 23 ) . In addition , in well-controlled socalled “ intensively ” treated patients , serious complications still occur ( 15–18,21 ) , and the economic and personal burden of diabetes remains . Furthermore , microvascular disease is already present in many individuals with undiagnosed or newly diagnosed type 2 diabetes ( 11,24– 28 ) . Given these facts , it is not surprising that studies have been initiated in the last decade to determine the feasibility and benefit of various strategies to prevent or delay the onset of type 2 diabetes . Two early reports ( 29,30 ) suggested that changes in lifestyle can prevent diabetes , but weaknesses in study design limited their general relevance . Recently , however , four well- design ed r and omized controlled trials have been reported ( 31–35 ) . In the Finnish study ( 31 ) , 522 middleaged ( mean age 55 years ) obese ( mean BMI 31 kg/m ) subjects with IGT were r and omized to receive either brief diet and exercise counseling ( control group ) or intensive individualized instruction on weight reduction , food intake , and guidance on increasing physical activity ( intervention group ) . After an average follow-up of 3.2 years , there was a 58 % relative reduction in the incidence of diabetes in the intervention group compared with the control subjects . A strong correlation was also seen between the ability to stop the progression to diabetes and the degree to which subjects were able to achieve one or more of the following : lose weight ( goal of 5.0 % weight reduction ) , reduce fat intake ( goal of 30 % of calories ) , reduce saturated fat intake ( goal of 10 % of calories ) , increase fiber intake ( goal of 15 g/1,000 kcal ) , and exercise ( goal of 150 min/week ) . No untoward effects of the lifestyle interventions were observed . In the Diabetes Prevention Program ( DPP ) ( 32–34 ) , the 3,234 enrolled subjects were slightly younger ( mean age 51 years ) and more obese ( mean BMI 34 kg/m ) but had nearly identical glucose intolerance compared with subjects in the Finnish study . About 45 % of the participants were from minority groups ( e.g , AfricanAmerican , Hispanic ) , and 20 % were 60 years of age . Subjects were r and omized to one of three intervention groups , which included the intensive nutrition and exercise counseling ( “ lifestyle ” ) group or either of two masked medication treatment groups : the biguanide metformin group or the placebo group . The latter interventions were combined with st and ard diet and exercise recommendations . After an average follow-up of 2.8 years ( range 1.8–4.6 years ) , a 58 % relative reduction in the progression to diabetes was observed in the lifestyle group ( absolute incidence 4.8 % ) , and a 31 % relative reduction in the progression of diabetes was observed in the metformin group ( absolute incidence 7.8 % ) compared with control subjects ( absolute incidence 11.0 % ) . ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● BACKGROUND Polyunsaturated fatty acids ( PUFAs ) and monounsaturated fatty acids ( MUFAs ) have been shown to positively affect blood lipids ; however , their comparative effects on insulin sensitivity are unclear . OBJECTIVE Our objective was to investigate whether chronic intake of MUFAs or PUFAs improves insulin sensitivity in people with type 2 diabetes via stimulation of the endogenous gut hormone glucagon-like peptide 1 [ 7 - 36 ] amide ( GLP-1 ) . DESIGN Nine overweight people with type 2 diabetes received isoenergetic high-MUFA ( 20.3 + /- 3.5 % of total energy ) or high-PUFA ( 13.4 + /- 1 . 3 % ) diets for 24 d in a r and omized , double-blind crossover design . RESULTS Weight and glycemic control remained stable throughout the study . Despite a significant change in the plasma triacylglycerol linoleic-oleic acid ratio ( L : O ) with both diets ( MUFA : from 0.46 + /- 0.03 to 0.29 + /- 0.02 , P : < 0.005 ; PUFA : from 0.36 + /- 0.04 to 0.56 + /- 0.05 , P : < 0.05 ) and the phospholipid L : O ( 1.7 + /- 0.1 to 2.0 + /- 0.3 ; P : = 0.04 ) during consumption of the PUFA diet , this change was not associated with a change in insulin sensitivity , measured by the short-insulin-tolerance test . There was a significant reduction in the ratio of total to HDL cholesterol during consumption of the PUFA diet ( 5.2 + /- 0.4 compared with 4.7 + /- 0.3 ; P : = 0.005 ) but no change with the MUFA diet . There was no change in the fasting or postpr and ial incremental area under the curve in response to an identical st and ard test meal for glucose , insulin , triacylglycerol , nonesterified fatty acids , or GLP-1 . CONCLUSIONS Over the 3-wk intervention period , diet-induced change in the triacylglycerol or phospholipid L : O was not associated with either increased stimulation of GLP-1 or a change in insulin sensitivity in people with type 2 diabetes Aims /hypothesis . The aim of the Diabetes Prevention Study is to assess the efficacy of an intensive diet-exercise programme in preventing or delaying Type II ( non-insulin-dependent ) diabetes mellitus in subjects with impaired glucose tolerance , to evaluate the effects of the intervention programme on cardiovascular risk factors and to assess the determinants for the progression to diabetes in persons with impaired glucose tolerance . Methods . A total of 523 overweight subjects with impaired glucose tolerance ascertained by two oral glucose tolerance tests were r and omised to either a control or intervention group . The control subjects received general information at the start of the trial about the lifestyle changes necessary to prevent diabetes and about annual follow-up visits . The intervention subjects had seven sessions with a nutritionist during the first year and a visit every 3 months thereafter aim ed at reducing weight , the intake of saturated fat and increasing the intake of dietary fibre . Intervention subjects were also guided individually to increase their physical activity . Results . During the first year , weight loss in the first 212 study subjects was 4.7 ± 5.5 vs 0.9 ± 4.1 kg in the intervention and control group , respectively ( p < 0.001 ) . The plasma glucose concentrations ( fasting : 5.9 ± 0.7 vs 6.4 ± 0.8 mmol/l , p < 0.001 ; and 2-h 7.8 ± 1.8 vs 8.5 ± 2.3 mmol/l , p < 0.05 ) were significantly lower in the intervention group after the first year of intervention . Favourable changes were also found in blood pressure , serum lipids and anthropometric indices in the intervention group . Conclusion /interpretation . The interim results show the efficacy and feasibility of the lifestyle intervention programme . [ Diabetologia ( 1999 ) 42 : 793–801 Context Weight loss and exercise decrease the development of diabetes in people with impaired glucose tolerance , but the effectiveness of these interventions in people with normal glucose tolerance is unknown . Contribution Using data from a large r and omized , controlled trial of cardiovascular disease prevention in men , the investigators show that participants with normal glucose tolerance at baseline developed diabetes at similar rates whether they received the diet and exercise intervention or usual care . However , the intervention was associated with lower risk of diabetes among nonsmokers . Implication s While diet and exercise may reduce the development of diabetes in nonsmokers with normal glucose metabolism at baseline , this benefit was not apparent among smokers . The Editors Epidemiologic studies have identified several potentially modifiable risk factors for type 2 diabetes mellitus , including obesity , a diet in which a high proportion of calories comes from fat , and low levels of physical activity ( 1 - 7 ) . Authorities have advocated that trials should test promising hypotheses about the primary prevention of type 2 diabetes ( 1 ) . R and omized intervention studies have demonstrated that , among those who already have impaired glucose tolerance , interventions that promote weight loss and increased exercise can reduce the risk for incident diabetes ( 8 - 10 ) . However , interventions should occur before at-risk individuals develop impaired glucose tolerance . A 2-year r and omized trial of diet , exercise , or both in individuals with a parental history of diabetes showed a statistically imprecise lower risk for developing diabetes in the intervention group ( 11 ) . To test such a hypothesis in groups who do not necessarily have a parental history of diabetes would be expensive . Strategies proposed for the primary prevention of type 2 diabetes include weight reduction , reduced dietary fat intake , and increased exercise ( 2 , 4 , 7 ) . These interventions are similar to those developed for preventing coronary heart disease ; therefore , examination of type 2 diabetes incidence rates in coronary heart disease prevention trials can provide preliminary evidence on the potential of such interventions to reduce type 2 diabetes risk . The Multiple Risk Factor Intervention Trial ( MRFIT ) enrolled 12866 middle-aged men at high risk for coronary heart disease and delivered either special intervention or usual care over 6 to 7 years . The research ers obtained fasting glucose values yearly , and participants self-reported their use of insulin or oral hypoglycemic agents . The glucose values and reports of diabetes medication use enable estimation of diabetes incidence during the trial . Previous reports from MRFIT have described risk factors for the development of diabetes in the usual care group ( 12 ) and the risk for death associated with incident diabetes in the combined special intervention and usual care groups ( 13 ) . In this paper , we compare the incidence of diabetes in the intervention and control groups of the MRFIT , report on an unexpected subgroup finding related to baseline cigarette smoking status , and explore reasons for the different results among smokers and nonsmokers . Methods Procedures Detailed descriptions of the MRFIT have been published ( 14 - 17 ) . Briefly , between 1973 and 1976 , the MRFIT investigators screened 361662 men for eligibility at 22 U.S. clinical centers . Of this group , 12866 men age 35 to 57 years were r and omly assigned : 6428 men to the special intervention group and 6438 men to the usual Output:

There are no high quality data on the efficacy of dietary intervention for the prevention of type 2 diabetes . More well- design ed , long-term studies , providing well-reported , high- quality data are required before proper conclusions can be made into the best dietary advice for the prevention of diabetes mellitus in adults

MS214185

***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 To study the effect of metformin before and during assisted reproductive technology ( ART ) on the clinical pregnancy rate ( CPR ) in non-obese women with polycystic ovary syndrome ( PCOS ) . METHODS A multi-centre , prospect i ve , r and omized , double-blind study was conducted in eight IVF clinics in four Nordic countries . We enrolled 150 PCOS women with a body mass index < 28 kg/m(2 ) , and treated them with 2000 mg/day metformin or identical placebo tablets for ≥ 12 weeks prior to and during long protocol IVF or ICSI and until the day of pregnancy testing . The primary outcome measure was CPR . Secondary outcome measures included spontaneous pregnancy rates during the pretreatment period , and the live birth rate ( LBR ) . RESULTS Among IVF treated women ( n = 112 ) , biochemical pregnancy rates were identical in both groups ( 42.9 % ) , and there were no significant differences in the metformin versus the placebo group in CPR [ 39.3 versus 30.4 % ; 95 % confidence interval ( CI ) : -8.6 to 26.5 ] . The LBR was 37.5 versus 28.6 % ( 95 % CI : -8.4 to 26.3 ) . However , prior to IVF there were 15 ( 20.3 % ) spontaneous pregnancies in the metformin group and eight ( 10.7 % ) in the placebo group ( 95 % CI : -1.9 to 21.1 ; P = 0.1047 ) . According to intention to treat analyses ( n = 149 ) ; significantly higher overall CPR were observed in the metformin versus placebo group ( 50.0 versus 33.3 % ; 95 % CI : -1.1 to 32.3 ; P = 0.0391 ) . LBR was also significantly higher with use of metformin versus placebo ( 48.6 versus 32.0 ; 95 % CI : 1.1 to 32.2 ; P = 0.0383 ) . No major unexpected safety issues or multiple births were reported . More gastrointestinal side effects occurred in the metformin group ( 41 versus 12 % ; 95 % CI : 0.15 to 0.42 ; P < 0.001 ) . CONCLUSIONS Metformin treatment for 12 weeks before and during IVF or ICSI in non-obese women with PCOS significantly increases pregnancy and LBRs compared with placebo . However , there was no effect on the outcome of ART per se . TRIAL REGISTRATION Clinical Trials.gov Identifier : NCT00159575 Estimates of the prevalence of the polycystic ovary syndrome ( PCOS ) in the general population have ranged from 2 - 20 % . The vast majority of these reports have studied White population s in Europe , used limited definitions of the disorder , and /or used bias population s , such as those seeking medical care . To estimate the prevalence of this disorder in the United States and address these limitations , we prospect ively determined the prevalence of PCOS in a reproductive-aged population of 369 consecutive women ( 174 White and 195 Black ; aged 18 - 45 yr ) , examined at the time of their preemployment physical . Body measures were obtained , and body hair was quantified by a modified Ferriman-Gallwey ( F-G ) method . All exams were initially performed by 2 trained nurses , and any subject with an F-G score above 3 was reexamined by a physician , the same for all patients . Of the 369 women , 277 ( 75.1 % ) also agreed to complete a question naire and have additional blood drawn . Subjects were studied regardless of current estrogen/progestin hormonal use ( 28.5 % ) . PCOS was defined as 1 ) oligoovulation , 2 ) clinical hyper and rogenism ( i.e. hirsutism ) and /or hyper and rogenemia , and 3 ) exclusion of other related disorders , such as hyperprolactinemia , thyroid abnormalities , and non-classic adrenal hyperplasia . Hirsutism was defined by a F-G score of 6 or more , and hyper and rogenemia was defined as a total or free testosterone , and rostenedione , and /or dehydroepi and rosterone sulfate level above the 95th percentile of control values [ i.e. all eumenorrheic women in the study , who had no hirsutism ( F-G < or = 5 ) or acne and were receiving no hormonal therapy ; n = 98 ] . Considering all 369 women studied , White and Black women had similar mean ages ( 29.4 + /- 7.1 and 31.1 + /- 7.8 yr , respectively ) , although White women had a lesser body mass than Black women ( 24.9 + /- 6.1 vs. 29.2 + /- 8.1 kg/m2 , respectively ; P < 0.001 ) . Of these 7.6 % , 4.6 % , and 1.9 % demonstrated a F-G score of 6 or more , 8 or 10 , respectively , and there was no significant racial difference , with hirsutism prevalences of 8.0 % , 2.8 % , and 1.6 % in Whites , and 7.1 % , 6.1 % , and 2.1 % in Blacks , respectively . Of the 277 women consenting to a history and hormonal evaluation , 4.0 % had PCOS as defined , 4.7 % ( 6 of 129 ) of Whites and 3.4 % ( 5 of 148 ) of Blacks . In conclusion , in our consecutive population of unselected women the prevalence of hirsutism varied from 2 - 8 % depending on the chosen cut-off F-G score , with no significant difference between White and Black women . Using an F-G score of 6 or more as indicative of hirsutism , 3.4 % of Blacks and 4.7 % of Whites had PCOS as defined . These data suggest that PCOS may be one of most common reproductive endocrinological disorders of women Gonadotrophin treatment in clomiphene citrate resistant polycystic ovarian syndrome ( PCOS ) patients , using either low-dose step-up or low-dose step-down protocol s , is highly effective to achieve singleton live births . Concomitant use of gonadotrophin releasing hormone analogues ( GnRHa ) , which will block the endogenous feedback for monofollicular development during the low-dose step-up protocol , should not be employed . It is more difficult to induce ovulation in patients with more ' severe ' PCOS , characterized by obesity and insulin resistance . There is need for optimization of starting doses for both the low-dose step-up and step-down protocol s. Such optimization will prevent hyperstimulation due to a starting dose far above the FSH threshold , as well as minimize the time-consuming low-dose increments by starting with a higher dose in women with augmented FSH threshold . External validation of reported models for prediction of FSH response is warranted for tailoring and optimizing treatment for everyday clinical practice . Although preliminary , the partial cessation of follicular development , along with regression leading to atresia , lends support to the LH ceiling theory , emphasizing the delicate balance and need for both FSH and LH in normal follicular development . Future well- design ed r and omized controlled trials will reveal whether IVF with or without in-vitro maturation of the oocytes will improve safety and efficacy compared with classical ovulation induction strategies OBJECTIVE To evaluate the effects of metformin on the ovarian response to gonadotropins given for in vitro fertilization ( IVF ) programs in patients with polycystic ovary syndrome ( PCOS ) and reduced ovarian reserve . DESIGN Prospect i ve , parallel , r and omized , double-blind , placebo-controlled clinical trial . SETTING Academic departments of obstetrics and gynecology , and a private IVF center . PATIENT(S ) Primary infertile patients with PCOS older than 35 years and /or with a basal follicle-stimulating hormone ( FSH ) level higher than 10 IU/L who were scheduled for IVF cycles . INTERVENTION(S ) Gonadotropin-releasing hormone agonist flare-up protocol and high starting doses of recombinant FSH plus metformin or placebo tablets . MAIN OUTCOME MEASURE(S ) Primary end point : cancellation rate for low ovarian response . Secondary end-points : other clinical , biochemical , and reproductive data . RESULT ( S ) Enrollment was stopped after 88 participants had been r and omized and analyzed due to an unacceptable increased risk of poor ovarian response in the metformin arm . Statistically significant differences between the metformin and placebo groups were observed in the dose of gonadotropins used , peak estradiol levels , and the number of dominant follicles , retrieved oocytes , and metaphase II oocytes . CONCLUSION ( S ) In patients with PCOS and reduced ovarian reserve , metformin worsened the response to gonadotropins , and its administration should be stopped before the start of controlled ovarian hyperstimulation for IVF programs . CLINICAL TRIALS IDENTIFICATION NUMBER : NCT01208740 BACKGROUND Our aim was to investigate the effect of pre-treatment with metformin in women with polycystic ovary syndrome ( PCOS ) scheduled for IVF stimulation . METHODS Seventy-three oligo/amenorrhoeic women with polycystic ovaries and at least one of the following criteria : hyper and rogenaemia , elevated LH/FSH ratio , hyperinsulinism , decreased SHBG levels or hirsutism , were studied . Normal weight and overweight patients were r and omized separately in a prospect i ve , r and omized , double blind study . All patients were treated for at least 16 weeks with metformin ( 1000 mg bid ) or placebo ending on the day of HCG injection . RESULTS No differences were found in the primary end-points : duration of FSH stimulation 14.4 ( 13.1 - 15.7 ) versus 14.2 ( 12.6 - 15.7 ) days or estradiol on the day of HCG injection 6.8 ( 5.3 - 8.2 ) versus 7.6 ( 5.6 - 9.6 ) nmol/l in the metformin and placebo groups , respectively . The secondary end-points number of oocytes , fertilization rates , embryo quality , pregnancy rates and clinical pregnancy rates were equal . However , in the normal weight subgroup ( BMI < 28 kg/m(2 ) , n = 27 ) , pregnancy rates following IVF were 0.71 ( 0.63 - 0.79 ) versus 0.23 ( 0.15 - 0.31 ) in the metformin and placebo groups , respectively ( P = 0.04 ) . Overall clinical pregnancy rates were equal : 0.51 ( 0.34 - 0.68 ) versus 0.44 ( 0.27 - 0.62 ) in the metformin and placebo groups , respectively . However , in the normal weight subgroup , clinical pregnancy rates were 0.67 ( 0.43 - 0.91 ) and 0.33 ( 0.06 - 0.60 ) , respectively ( P = 0.06 ) . CONCLUSIONS Pre-treatment with metformin prior to conventional IVF/ICSI in women with PCOS does not improve stimulation or clinical outcome . However , among normal weight PCOS women , pre-treatment with metformin tends to improve pregnancy rates . Further studies in subgroups of PCOS women are required BACKGROUND Metformin appears to improve reproductive function in some women with polycystic ovary syndrome ( PCOS ) . We wished to explore the effect of metformin in women with PCOS undergoing IVF . METHODS A r and omized , placebo-controlled , double-blind study was carried out between 2001 and 2004 . Patients with PCOS undergoing IVF/ICSI treatment using a long GnRH agonist protocol were r and omized to receive metformin ( MET ) , 850 mg , or placebo ( PLA ) tablets twice daily from the start of the down-regulation process until the day of oocyte collection . The primary outcome was to be an improvement in the overall fertilization rate . RESULTS One-hundred and one IVF/ICSI cycles were r and omized to receive metformin ( 52 ) or to receive placebo ( 49 ) . There was no difference in the total dose of rFSH required per cycle ( median dose : MET = 1200 U , PLA = 1300 U ; P = 0.937 ) . The median number of oocytes retrieved per cycle ( MET = 17.2 , PLA = 16.2 ; P = 0.459 ) and the overall fertilization rates ( MET = 52.9 % , PLA = 54.9 % ; P = 0.641 ) did not differ . However , both the clinical pregnancy rates beyond 12 weeks gestation per cycle ( MET = 38.5 % , PLA = 16.3 % ; P = 0.023 ) and per embryo transfer ( MET = 44.4 % , PLA = 19.1 % ; P = 0.022 ) were significantly higher in those treated with metformin . Furthermore , Output:

This review found no conclusive evidence that metformin treatment before or during ART cycles improved live birth rates in women with PCOS . However , the use of this insulin-sensitising agent increased clinical pregnancy rates and decreased the risk of OHSS

MS214186

***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 This study evaluated whether intervening with child care providers would increase physical activity ( PA ) and reduce adiposity in preschoolers . METHODS This was a two-arm , parallel group , cluster RCT whereby six child care centers were r and omly assigned in equal numbers to intervention ( n=40 children ) or control ( n=43 children ) . Participants were aged 3 - 5 years and attended licensed child care centers . Child care providers received two 3-hour train-the-trainer workshops and a training manual at program initiation aim ed at increasing structured and unstructured PA through active play . Control child care centers implemented their st and ard curriculum . PA and sedentary behavior were measured by accelerometry , and body composition was measured using bioelectrical impedance at baseline and 6 months . Data were collected in 2011 - 2012 and analyzed in April 2015 . RESULTS Linear mixed-effects modeling showed that at 6 months , children in the intervention group demonstrated greater increases in minutes per preschool day spent in overall PA ( 22.5 minutes , 95 % CI=8.9 , 36.1 , p=0.002 ) , and light-intensity PA ( 16.1 minutes , 95 % CI=5.2 , 26.7 , p=0.004 ) , but changes between groups in moderate to vigorous PA did not differ . The intervention group showed greater reductions in body fat percentage ( -1.9 % , 95 % CI=-3.5 , -0.3 , p=0.023 ) and fat mass ( -0.3 kg , 95 % CI=-0.7 , -0.1 , p=0.018 ) , but groups did not differ on fat-free mass , BMI , or z- BMI . CONCLUSIONS Provider-led intervention in child care centers increased preschoolers ' PA and reduced adiposity , therefore may represent a viable approach to promoting PA and related health benefits in preschool-aged children . TRIAL REGISTRATION This study is registered at www . clinical trials.gov NCT02293278 BACKGROUND Sugar-sweetened beverages and maternal weight are strong drivers of child obesity , but few studies have targeted these risk factors as an obesity prevention strategy in children . OBJECTIVE The objective of this study was to test the efficacy of a smartphone-delivered intervention to reduce parent-provided sugar-sweetened beverage and juice ( SSB/juice ) consumption among children ages 3 - 5 and maternal weight . METHODS Mothers with overweight or obesity , who had a child ages 3 - 5 that consumed at least 12 fl . oz./day of SSB/juice ( N = 51 dyads ) were r and omized to the Smart Moms group that received one group session , lessons on a mobile website , and text messages , or to a waitlist control group . Mothers self-monitored their children 's beverages in addition to their own beverages , high-calorie foods , and weight . Assessment s at baseline , 3 , and 6 months included dietary recalls to measure SSB/juice intake and objective ly measured maternal weight . RESULTS Using linear mixed models controlling for baseline values , child age and race , there was a greater reduction in child SSB/juice in Smart Moms compared with control at 6 months ( -9.7 oz./day vs. 1.7 oz./day , p < .01 ) . Mothers in Smart Moms lost 2.4 kg at 6 months compared with a 0.9-kg gain in the control group ( p < .01 ) . CONCLUSIONS An intervention delivered using mHealth technologies can target mothers to change child dietary behaviours and improve maternal weight , which suggests a novel approach to family-based obesity prevention Background The primary aim of this study was to evaluate the effectiveness of an intervention to increase the implementation of healthy eating and physical activity policies and practice s by centre-based childcare services . The study also sought to determine if the intervention was effective in improving child dietary intake and increasing child physical activity levels while attending childcare . Methods A parallel group , r and omised controlled trial was conducted in a sample of 128 childcare services . Intervention strategies included provision of implementation support staff , securing executive support , staff training , consensus processes , academic detailing visits , tools and re sources , performance monitoring and feedback and a communications strategy . The primary outcome of the trial was the proportion of services implementing all seven healthy eating and physical activity policies and practice s targeted by the intervention . Outcome data were collected via telephone surveys with nominated supervisors and room leaders at baseline and immediately post-intervention . Secondary trial outcomes included the differences between groups in the number of serves consumed by children for each food group within the Australian Guide to Healthy Eating and in the proportion of children engaged in sedentary , walking or very active physical activity assessed via observation in a r and om sub sample of 36 services at follow-up . Results There was no significant difference between groups for the primary trial outcome ( p = 0.44 ) . Relative to the control group , a significantly larger proportion of intervention group services reported having a written nutrition and physical activity policy ( p = 0.05 ) and providing adult-guided activities to develop fundamental movement skills ( p = 0.01 ) . There were no significant differences between groups at follow-up on measures of child dietary intake or physical activity . Conclusions The findings of the trial were equivocal . While there was no significant difference between groups for the primary trial outcome , the intervention did significantly increase the proportion of intervention group services implementing two of the seven healthy eating and physical activity policies and practice s. High levels of implementation of a number of policies and practice s at baseline , significant obesity prevention activity in the study region and higher than previously reported intra-class correlation of child behaviours may , in part , explain the trial findings .Trial registration Australian Clinical Trials Registry ( reference ACTRN12612000927820 ) BACKGROUND The prevalence of obesity in the United States is a significant public health problem . Many obesity-related risk factors are more prevalent in minority population s. Given the recalcitrant nature of weight loss interventions for adults , prevention of overweight and obesity has become a high priority . The present study reports baseline data from an obesity prevention intervention developed for minority preschool children . METHODS Hip-Hop to Health Jr. is a 5-year r and omized controlled intervention that targets 3- to 5-year-old minority children enrolled in 24 Head Start programs . Our primary aim is to test the effect of the intervention on change in body mass index . Data were collected on sociodemographic , anthropometric , behavioral , and cognitive variables for the children and parents at baseline . RESULTS Participants included 416 black children , 337 black parents , 362 Latino children , and 309 Latino parents . Using body mass index for age and sex > or = the 95th percentile as the definition of overweight , 15 % of the black children and 28 % of the Latino children were overweight . More than 75 % of the parents were either overweight or obese . DISCUSSION The development of interventions to effectively prevent or control obesity early in life is crucial . These data highlight the escalating problem of weight control in minority population Background Little is known about preschool-aged children ’s levels of physical activity ( PA ) over the course of the day . Using time-stamped data , we describe the levels and patterns of PA in a population -based sample of four-year-old British children . Methods Within the Southampton Women ’s Survey the PA levels of 593 4-year-old children ( 51 % female ) were measured using ( Actiheart ) accelerometry for up to 7 days . Three outcome measures : minutes spent sedentary ( < 20 cpm ) ; in light ( LPA : ≥20 – 399 cpm ) and in moderate-to-vigorous activity ( MVPA : ≥400 cpm ) were derived . Average daily activity levels were calculated and then segmented across the day ( morning , afternoon and evening ) . MVPA was log-transformed . Two-level r and om intercept models were used to analyse associations between activity level and temporal and demographic factors . Results Children were active for 67 % ( mean 568.5 SD 79.5 minutes ) of their daily registered time on average , with 88 % of active time spent in LPA . All children met current UK guidelines of 180 minutes of daily activity . There were no differences in children ’s average daily levels of sedentary activity and LPA by temporal and demographic factors : differences did emerge when activity was segmented across the day . Sex differences were largest in the morning , with girls being more sedentary , spending fewer minutes in LPA and 18 % less time in MVPA than boys . Children were more sedentary and less active ( LPA and MVPA ) in the morning if they attended childcare full-time compared to part-time , and on weekend mornings compared to weekdays . The reverse was true for weekend afternoons and evenings . Children with more educated mothers were less active in the evenings . Children were less sedentary and did more MVPA on summer evenings compared to winter evenings . Conclusions Preschool-aged children meet current physical activity guidelines , but with the majority of their active time spent in LPA , investigation of the importance of activity intensity in younger children is needed . Activity levels over the day differed by demographic and temporal factors , highlighting the need to consider temporality in future interventions . Increasing girls ’ morning activity and providing opportunities for daytime activity in winter months may be worthwhile Background There is considerable scope to improve the delivery of practice s that increase the physical activity of children in centre based childcare services . Few studies have reported the effectiveness of interventions to address this , particularly at a population level . The primary aim of this study was to describe the impact of an intervention to increase the adoption of multiple policies and practice s to promote physical activity in centre based childcare services . Methods A quasi experimental study was conducted in centre based childcare services ( n = 228 ) in New South Wales ( NSW ) , Australia and involved a three month intervention to increase the adoption of eight practice s within childcare services that have been suggested to promote child physical activity . Intervention strategies to support the adoption of practice s included staff training , re sources , incentives , follow-up support and performance monitoring and feedback . R and omly selected childcare services in the remainder of NSW acted as a comparison group ( n = 164 ) and did not receive the intervention but may have been exposed to a concurrent NSW government healthy eating and physical activity initiative . Self reported information on physical activity policies , fundamental movement skills sessions , structured physical activity opportunities , staff involvement in active play and provision of verbal prompts to encourage physical activity , small screen recreation opportunities , sedentary time , and staff trained in physical activity were collected by telephone survey with childcare service managers at baseline and 18 months later . Results Compared with the comparison area , the study found significantly greater increases in the prevalence of intervention services with a written physical activity policy , with policy referring to placing limits on small screen recreation , and with staff trained in physical activity . In addition , non-significant trends towards a greater increase in the proportion of intervention services conducting daily fundamental movement skill sessions , and such services having a physical activity policy supporting physical activity training for staff were also evident . Conclusion The intervention was effective in improving a number of centre based childcare service policies and practice s associated with promoting child physical activity . Adoption of a broader range of practice s may require more intensive and prolonged intervention support OBJECTIVE Determine whether Color Me Healthy ( CMH ) , an interactive nutrition and physical activity program for preschool children , increases fruit and vegetable consumption . DESIGN Intervention study . Data were collected at baseline , 1 week post-intervention , and 3 months post-intervention . SETTING Child care centers . PARTICIPANTS Preschool children ( n = 263 ) in 17 child care centers . INTERVENTION Child care centers were r and omly assigned to 1 of 2 conditions ; children ( n = 165 ) in 10 centers received the CMH curriculum , and children ( n = 98 ) in 7 centers acted as comparisons and did not receive the curriculum . MAIN OUTCOME MEASURES Process and outcome evaluation . Consumption of fruit and vegetable snacks . ANALYSIS Data were analyzed using repeated- measures analysis of variance and hierarchical linear modeling . RESULTS Children who received CMH significantly increased their consumption of fruit snacks by approximately 20.8 % and vegetable snacks by approximately 33.1 % between baseline assessment and the assessment conducted 3 months after the completion of the CMH program . Hierarchical linear modeling determined that group assignment ( ie , CMH or control ) was the only significant predictor of fruit and vegetable consumption . CONCLUSIONS AND IMPLICATION S Findings suggest that CMH may be used in child care setting s for developing healthful eating habits BACKGROUND The Child Health Initiative for Lifelong Eating and Exercise is a multicomponent obesity-prevention intervention , which was evaluated among Head Start ( HS ) centers in American Indian and predominantly Hispanic communities in rural New Mexico . This study examines the intervention 's foodservice outcomes : fruits , vegetables , whole grains , discretionary fats , added sugars , and fat from milk served in meals and snacks . METHODS Sixteen HS centers were r and omized to intervention/comparison groups , following stratification by ethnicity and preintervention median body mass index of enrolled children . The foodservice component included quarterly trainings for foodservice staff about food purchasing and preparation . Foods served were evaluated before and after the 2-year intervention , in the fall 2008 and spring 2010 . RESULTS The intervention significantly decreased fat provided through milk and had no significant effect on fruit , vegetables and whole-grain servings , discretionary fats , and added sugar served in HS meals and snacks . When effect modification by site ethnicity was examined , the effect on fat provided through milk was only found in American Indian sites . CONCLUSIONS Foodservice interventions Output:

It is uncertain whether the strategies tested improved the implementation of policies , practice s or programmes that promote child healthy eating , physical activity and /or obesity prevention . No intervention improved the implementation of all policies and practice s targeted by the implementation strategies relative to a comparison group . Current research provides weak and inconsistent evidence of the effectiveness of such strategies in improving the implementation of policies and practice s , childcare service staff knowledge or attitudes , or child diet , physical activity or weight status .

MS214187

***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: Pilot studies for phase III trials - which are comparative r and omized trials design ed to provide preliminary evidence on the clinical efficacy of a drug or intervention - are routinely performed in many clinical areas . Also commonly know as " feasibility " or " vanguard " studies , they are design ed to assess the safety of treatment or interventions ; to assess recruitment potential ; to assess the feasibility of international collaboration or coordination for multicentre trials ; to increase clinical experience with the study medication or intervention for the phase III trials . They are the best way to assess feasibility of a large , expensive full-scale study , and in fact are an almost essential pre-requisite . Conducting a pilot prior to the main study can enhance the likelihood of success of the main study and potentially help to avoid doomed main studies . The objective of this paper is to provide a detailed examination of the key aspects of pilot studies for phase III trials including : 1 ) the general reasons for conducting a pilot study ; 2 ) the relationships between pilot studies , proof-of-concept studies , and adaptive design s ; 3 ) the challenges of and misconceptions about pilot studies ; 4 ) the criteria for evaluating the success of a pilot study ; 5 ) frequently asked questions about pilot studies ; 7 ) some ethical aspects related to pilot studies ; and 8) some suggestions on how to report the results of pilot investigations using the CONSORT format Background Falls among hospitalised patients impose a considerable burden on health systems globally and prevention is a priority . Some patient-level interventions have been effective in reducing falls , but others have not . An alternative and promising approach to reducing inpatient falls is through the modification of the hospital physical environment and the night lighting of hospital wards is a leading c and i date for investigation . In this pilot trial , we will determine the feasibility of conducting a main trial to evaluate the effects of modified night lighting on inpatient ward level fall rates . We will test also the feasibility of collecting novel forms of patient level data through a concurrent observational sub- study . Methods / design A stepped wedge , cluster r and omised controlled trial will be conducted in six inpatient wards over 14 months in a metropolitan teaching hospital in Brisbane ( Australia ) . The intervention will consist of supplementary night lighting installed across all patient rooms within study wards . The planned placement of luminaires , configurations and spectral characteristics are based on prior published research and pre-trial testing and modification . We will collect data on rates of falls on study wards ( falls per 1000 patient days ) , the proportion of patients who fall once or more , and average length of stay . We will recruit two patients per ward per month to a concurrent observational sub- study aim ed at underst and ing potential impacts on a range of patient sleep and mobility behaviour . The effect on the environment will be monitored with sensors to detect variation in light levels and night-time room activity . We will also collect data on possible patient-level confounders including demographics , pre-admission sleep quality , reported vision , hearing impairment and functional status . Discussion This pragmatic pilot trial will assess the feasibility of conducting a main trial to investigate the effects of modified night lighting on inpatient fall rates using several new methods previously untested in the context of environmental modifications and patient safety . Pilot data collected through both parts of the trial will be utilised to inform sample size calculations , trial design and final data collection methods for a subsequent main trial . Trial registration Australian New Zeal and Clinical Trials Register ( ANZCTR ) : ACTRN12614000615684 ( cluster RCT ) and ACTRN12614000616673 ( observational sub- study ) . Date Registered : 10 June 2014 ( both studies ) . Protocol version : 1.2 ( Date d : 01 June 2014)Anticipated completion : September 2015Role of Trial Sponsor : The named sponsor for this investigator-initiated trial was the Director of the Royal Brisbane and Women ’s Hospital ( RBWH ) Safety and Quality Unit ( Therese Lee , Phone : + 61 7 3646 8111 ) . The principal investigators , SC and MA , are employed by the RBWH Safety and Quality Unit . The trial sponsor has no involvement in any aspects of study design , conduct or decision to su bmi t the report for publication . AM and MD are employed by other departments in the same organisation BACKGROUND A crucial part in the development of any intervention is the preliminary work carried out prior to a large-scale definitive trial . However , the definitions of these terms are not clear cut and many authors redefine them . Because of this , the terms feasibility and pilot are often misused . AIM To provide an introduction to the topic area of pilot and feasibility trials and draw together the work of others in the area on defining what is a pilot or feasibility study . METHODS This study used a review of definitions and advice from the published literature and from funders ' websites . Examples are used to show evidence of good practice and poor practice . RESULTS We found that research ers use different terms to describe the various stages of the research process . Some define the terms feasibility and pilot as being different whereas others argue that these terms are synonymous . All reflective papers agree that feasibility/pilot studies should not test treatment comparisons nor estimate feasible effect sizes . However , this is not universally observed in practice . SUMMARY We believe that the term ' feasibility ' should be used as an overarching term for preliminary studies and the term ' pilot ' refers to a specific type of study which resembles the intended trial in aspects such as , having a control group and r and omisation . However , studies labelled ' pilot ' should have different aims and objectives to main trials and also should include an intention for future work . Research ers should not use the title ' pilot ' for a trial which evaluates a treatment effect OBJECTIVES To determine the advantages and disadvantages of a stepped wedge design for a specific clinical application . STUDY DESIGN AND SETTING The clinical application was a pragmatic cluster r and omized surgical trial intending to find an increased percentage of curable recurrences in patients in follow-up after colorectal cancer . Advantages and disadvantages of the stepped wedge design were evaluated , and for this application , new advantages and disadvantages were presented . RESULTS A main advantage of the stepped wedge design was that the intervention rolls out to all participants , motivating patients and doctors , and a large number of patients who were included in this study . The stepped wedge design increased the complexity of the data analysis , and there were concerns regarding the informed consent procedure . The repeated measurements may bring burden to patients in terms of quality of life , satisfaction , and costs . CONCLUSION The stepped wedge design is a strong alternative for pragmatic cluster r and omized trials . The known advantages hold , whereas most of the disadvantages were not applicable to this application . The main advantage was that we were able to include a large number of patients . Main disadvantages were that the informed consent procedure can be problematic and that the analysis of the data can be complex Background A pragmatic , stepped wedge trial design can be an appealing design to evaluate complex interventions in real-life setting s. However , there are certain pitfalls that need to be considered . This paper reports on the experiences and lessons learned from the conduct of a cluster r and omized , stepped wedge trial evaluating the effect of the Hospital Elder Life Program ( HELP ) in a Dutch hospital setting to prevent older patients from developing delirium . Methods We evaluated our trial which was conducted in eight departments in two hospitals in hospitalized patients aged 70 years or older who were at risk for delirium by reflecting on the assumptions that we had and on what we intended to accomplish when we started , as compared to what we actually realized in the different phases of our study . Lessons learned on the design , the timeline , the enrollment of eligible patients and the use of routinely collected data are provided accompanied by recommendations to address challenges . Results The start of the trial was delayed which caused subsequent time schedule problems . The requirement for individual informed consent for a quality improvement project made the inclusion more prone to selection bias . Most units experienced major difficulties in including patients , leading to excluding two of the eight units from participation . This result ed in failing to include a similar number of patients in the control condition versus the intervention condition . Data on outcomes routinely collected in the electronic patient records were not accessible during the study , and appeared to be often missing during analyses . Conclusions The stepped wedge , cluster r and omized trial poses specific risks in the design and execution of research in real-life setting s of which research ers should be aware to prevent negative consequences impacting the validity of their results . Valid conclusions on the effectiveness of the HELP in the Dutch hospital setting are hampered by the limited quantity and quality of routine clinical data in our pragmatic trial . Executing a stepped wedge design in a daily practice setting using routinely collected data requires specific attention to ethical review , flexibility , a spacious time schedule , the availability of substantial capacity in the research team and early checks on the data availability and quality .Trial registration Netherl and s Trial Register , identifier : NTR3842 . Registered on 24 January 2013 Research ers should consider five questions before starting a stepped wedge trial . Why are you planning one ? Research ers sometimes think that stepped wedge trials are useful when there is little doubt about the benefit of the intervention being tested . However , if the primary reason for an intervention is to measure its effect , without equipoise there is no ethical justification for delaying implementation in some clusters . By contrast , if you are undertaking pragmatic research , where the primary reason for rolling out the intervention is for it to exert its benefits , and if phased implementation is inevitable , a stepped wedge trial is a valid option and provides better evidence than most non-r and omized evaluations . What design will you use ? Two common stepped wedge design s are based on the recruitment of a closed or open cohort . In both , individuals may experience both control and intervention conditions and you should be concerned about carry-over effects . In a third , continuous-recruitment , short-exposure design , individuals are recruited as they become eligible and experience either control or intervention condition , but not both . How will you conduct the primary analysis ? In stepped wedge trials , control of confounding factors through secular variation is essential . ‘ Vertical ’ approaches preserve r and omization and compare outcomes between r and omized groups within periods . ‘ Horizontal ’ approaches compare outcomes before and after crossover to the intervention condition . Most analysis models used in practice combine both types of comparison . The appropriate analytic strategy should be considered on a case-by-case basis . How large will your trial be ? St and ard sample size calculations for cluster r and omized trials do not accommo date the specific features of stepped wedge trials . Methods exist for many stepped wedge design s , but simulation-based calculations provide the greatest flexibility . In some scenarios , such as when the intracluster correlation coefficient is moderate or high , or the cluster size is large , a stepped wedge trial may require fewer clusters than a parallel cluster trial . How will you report your trial ? Stepped wedge trials are currently challenging to report using CONSORT principles . Research ers should consider how to demonstrate balance achieved by r and omization and how to describe trends for outcomes in both intervention and control clusters Background : Shared decision making is important to ensure that patients receive therapies aligned with their goals and values . Based upon a detailed needs assessment with diverse stakeholders , pamphlet and video decision aids for destination therapy left ventricular assist devices ( DT LVAD ) were developed to help patients and their caregivers think through , forecast , and deliberate their options . These decision aids are the foundation of the Multicenter Trial of a Shared Decision Support Intervention for Patients and their Caregivers Offered Destination Therapy for End-Stage Heart Failure ( DECIDE-LVAD ) study , a multicenter , r and omized trial aim ed at underst and ing the effectiveness and implementation of a shared decision support intervention for patients considering DT LVAD . Methods / Design : A stepped-wedge r and omized controlled trial was design ed , guided by the RE- AIM framework and modeled after an effectiveness-implementation hybrid type II design . Six DT LVAD programs from across the United States will participate . Primary outcomes include knowledge and values-treatment concordance . Patients with advanced heart failure who are being considered for DT LVAD and their caregivers are eligible with a target enrollment of 168 dyads . From August 2014 to January 2015 , an acceptability and feasibility pilot study was performed , which clarified opportunities and challenges around decision support for DT LVAD and result ed in significant modifications to the DECIDE-LVAD study . Discussion : Study findings will provide a foundation for implementing decision support interventions , including decision aids , with patients who have chronic progressive illness facing end-of-life decisions involving invasive , preference-sensitive therapy options We describe a framework for defining pilot and feasibility studies focusing on studies conducted in preparation for a r and omised controlled trial . To develop the framework , we undertook a Delphi survey ; ran an open meeting at a trial methodology conference ; conducted a review of definitions outside the health research context ; consulted experts at an international consensus meeting ; and review ed 27 empirical pilot or feasibility studies . We initially adopted mutually exclusive definitions of pilot and feasibility studies . However , some Delphi survey respondents and the majority of open meeting attendees disagreed with the idea of mutually exclusive definitions . Their viewpoint was supported by definitions outside the health research context , the use of the terms ‘ pilot ’ and ‘ feasibility ’ in the literature , and participants at the international consensus meeting . In our framework , pilot studies are a subset of feasibility studies , rather than the two being mutually exclusive . A feasibility study asks whether something can be done , should we proceed with it , and if so , how . A pilot study asks the same questions but also has a specific design feature : in a pilot study a future study , or part of a future study , is conducted on a smaller scale . We suggest that to facilitate their identification , these studies should be clearly identified using the terms ‘ feasibility ’ or ‘ pilot ’ as appropriate . This should include feasibility studies that are largely qualitative ; we found these difficult to identify in electronic search es because research ers rarely used the term ‘ feasibility ’ in the title or abstract of such studies . Investigators should also report appropriate objectives and methods related to feasibility ; and give clear confirmation that their study is in preparation for a future r and omised controlled trial design ed to assess the effect of an intervention The Consoli date d St and ards of Reporting Trials ( CONSORT ) statement is a guideline design ed to improve the transparency and quality of the reporting of r and omised controlled trials ( RCTs ) Output:

Conclusion Published feasibility studies for SW-CRTs are scarce and those that are being reported do not investigate issues specific to the complexities of the trial design .