Testosterone replacement therapy in older male subjective memory complainers: double-blind randomized crossover placebo-controlled clinical trial of physiological assessment and safety. 12-Month Observation of Testosterone Replacement Effectiveness in a General Population of Men Effect of testosterone replacement therapy on prostate tissue in men with late-onset hypogonadism: a randomized controlled trial. Testosterone deficiency is associated with increased risk of mortality and testosterone replacement improves survival in men with type 2 diabetes. The effect of hormone replacement therapy and route of administration on selected cardiovascular risk factors in post-menopausal women. Effects of individual risk factors on the incidence of cardiovascular events in the treated hypertensive patients of the Hypertension Optimal Treatment Study. HOT Study Group. Microalbuminuria as an early marker for cardiovascular disease. Cardiovascular risk in relation to body mass index and use of evidence-based preventive medications in patients with or at risk of atherothrombosis. Is Reducing Ovarian Volume in Polycystic Ovarian Syndrome Patients after Administration of Metformin Associated with Improving Cardiovascular Risk Factors? Infectious risk of replacing venous catheters by the guide-wire technique. Rationale, design, and baseline characteristics of a randomized, placebo-controlled cardiovascular outcome trial of empagliflozin (EMPA-REG OUTCOME™) Task-related training combined with transcutaneous electrical nerve stimulation promotes upper limb functions in patients with chronic stroke. Randomised evaluation of a specific training of general practitioners in cardiovascular prevention The effect of resistance training set configuration on strength, power, and hormonal adaptation in female volleyball players. Multimodal therapy for the management of nonpelvic, localized Ewing's sarcoma of bone: intergroup study IESS-II. Psychosocial stress and major cardiovascular events in patients with stable coronary heart disease Advanced chronic kidney disease populations have elevated trimethylamine N-oxide levels associated with increased cardiovascular events. Use of Oseltamivir After Influenza Infection Is Associated With Reduced Incidence of Recurrent Adverse Cardiovascular Outcomes Among Military Health System Beneficiaries With Prior Cardiovascular Diseases Long-Term Clinical Trial of Tinnitus Retraining Therapy Relation of vitamin D deficiency to cardiovascular risk factors, disease status, and incident events in a general healthcare population. Association of baseline risk factors with cardiovascular (CV) events during long-term degarelix therapy in men with prostate cancer. Cardiovascular outcomes in the African American Study of Kidney Disease and Hypertension (AASK) Trial. Preventing cardiovascular disease in women: an intervention-control randomized study. Incidence and risk factors of atherosclerotic cardiovascular accidents in predialysis chronic renal failure patients: a prospective study. Is a targeted and planned GP intervention effective in cardiovascular disease prevention? A randomized controlled trial The design and rationale for the Dapagliflozin Effect on Cardiovascular Events (DECLARE)–TIMI 58 Trial The CHADS2 and CHA2DS2-VASc scores predict adverse vascular function, ischemic stroke and cardiovascular death in high-risk patients without atrial fibrillation: role of incorporating PR prolongation. A Systematic Assessment of Cardiovascular Outcomes in the Saxagliptin Drug Development Program for Type 2 Diabetes Serum testosterone levels and clinical outcomes in male hemodialysis patients. Cardiovascular complications in patients with advanced prostatic cancer treated by means of orchiectomy or polyestradiol phosphate Year-by-year analysis of cardiovascular events in the Multiple Outcomes of Raloxifene Evaluation (MORE) trial* Increasing hematocrit reduces early posttransplant cardiovascular risk in diabetic transplant recipients1 Effect of ketoprofen on muscle function and sEMG activity after eccentric exercise. Short term testosterone replacement therapy improves libido and body composition. Efficacy of High Intensity Exercise on Disease Activity and Cardiovascular Risk in Active Axial Spondyloarthritis: A Randomized Controlled Pilot Study Effects of therapeutic lifestyle changes on peripheral artery tonometry in patients with abdominal obesity. The prognostic impact of in-hospital worsening of renal function in patients with acute coronary syndrome. Transcutaneous Electrical Nerve Stimulation Combined With Task-Related Training Improves Lower Limb Functions in Subjects With Chronic Stroke Explaining the cardiovascular risk associated with rheumatoid arthritis: traditional risk factors versus markers of rheumatoid arthritis severity The effect of pharmacological therapy on the cardiovascular system of patients with systemic rheumatic diseases. Rehabilitation of reaching after stroke: task-related training versus progressive resistive exercise. Allopurinol and progression of CKD and cardiovascular events: long-term follow-up of a randomized clinical trial. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410.
Testosterone replacement therapy ( TRT ) has been investigated in older men as a preventative treatment against Alzheimer 's disease and dementia . However , previous studies have been contradictory . We assessed TRT physiological effects in 44 older men ( aged 61 ± 7.7 years ) with subjective memory complaints using a double blind , r and omized , crossover , placebo-controlled study . Participants were r and omized into 2 groups , one group received transdermal testosterone ( 50 mg ) daily for 24 weeks , followed by a 4 week wash-out period , then 24 weeks of placebo ; the other group received the reverse treatment . Blood evaluation revealed significant increases in total testosterone , free ( calculated ) testosterone , dihydrotestosterone , and a decrease in luteinizing hormone levels ( p<0.001 ) following TRT . Although there were significant increases in red blood cell counts , hemoglobin and prostate specific antigen levels  following TRT , they remained within normal ranges . No significant differences in plasma amyloid beta , estradiol , sex hormone binding globulin , insulin levels , body fat percentage , or body mass index were detected . This is the first carefully controlled study that has investigated the influence of TRT in Indonesian men  on blood biomarkers linked to dementia risk . Our study suggests TRT is safe and well-tolerated in this Indonesian cohort , yet longitudinal studies with larger cohorts are needed to assess TRT further , and to establish whether TRT  reduces dementia risk Abstract Background : Testosterone decline becomes more prevalent as men age and symptomatic testosterone deficiency is associated with potentially serious comorbidities . Despite limitations , registries can provide an opportunity to accumulate data regarding disease management in a typical patient population , including diagnosis , treatment , and outcomes . Material s and Methods : The Testim Registry in the United States ( TRiUS ) was a prospect i ve , 12-month , observational cohort registry of men prescribed Testim ® ( 1 % testosterone gel ; Auxilium Pharmaceuticals , Inc. ) for the first time ; patients previously on other forms of testosterone replacement therapy ( TRT )  were eligible to participate in the study as well . The registry recorded total testosterone ( TT ) and free testosterone ( FT ) levels , prostate-specific antigen ( PSA ) , sexual function , mood/depression , and cardiometabolic and anthropometric criteria before and after TRT . Changes over time were analyzed by analysis of variance , and linear regression and Pearson product-moment correlation coefficients were used to examine relationships between variables . Results : At baseline , 849 patients from 72 sites were enrolled , with 743 of 849 started on 5 g gel/day ( 50 mg testosterone/day ) and 106 of 849 started on 10 g gel/day ( 100 mg testosterone/day ) . Mean TT and FT levels increased significantly after 3 months of TRT ( TT level , 16.8 ± 9.87 nmol/L [ 485 ± 284 ng/dL ] , P < 0.001 ; FT level , 286.3 ± 224.9 pmol/L [ 82.5 ± 64.8 pg/mL ] , P < 0.001 ) and were maintained at eugonadal levels . Mean PSA levels increased significantly ( P = 0.004 ) from 1.12 ± 1.11 μg/L ( 1.12 + 1.11 ng/mL ) at baseline to 1.26 ± 1.22 μg/L ( 1.26 ± 1.22 ng/mL ) after 12 months of TRT , although changes were well within guidelines ( < 1.4 μg/L/year increase ) . Significant improvements were seen in sexual function and mood/depression at 3 months and in metabolic parameters at 12 months . Conclusion : Testosterone deficiency symptoms improved with TRT use in men ; sexual function and mood/depression improvements were seen before metabolic improvements . Prostate-specific antigen levels increased , although increases were within guideline -determined safety limits CONTEXT Prostate safety is a primary concern when aging men receive testosterone replacement therapy ( TRT ) , but little information is available regarding the effects of TRT on prostate tissue in men . OBJECTIVE To determine the effects of TRT on prostate tissue of aging men with low serum testosterone levels . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled trial of 44 men , aged 44 to 78 years , with screening serum testosterone levels lower than 300 ng/dL ( < 10.4 nmol/L ) and related symptoms , conducted at a US community-based research center between February 2003 and November 2004 . INTERVENTION Participants were r and omly assigned to receive 150 mg of testosterone enanthate or matching placebo intramuscularly every 2 weeks for 6 months . MAIN OUTCOME MEASURES The primary outcome measure was the 6-month change in prostate tissue and rogen levels ( testosterone and dihydrotestosterone ) . Secondary outcome measures included 6-month changes in prostate-related clinical features , histology , biomarkers , and epithelial cell gene expression . RESULTS Of the 44 men r and omized , 40 had prostate biopsies performed both at baseline and at 6 months and qualified for per- protocol analysis ( TRT , n = 21 ; placebo , n = 19 ) . Testosterone replacement therapy increased serum testosterone levels to the mid-normal range ( median at baseline , 282 ng/dL [ 9.8 nmol/L ] ; median at 6 months , 640 ng/dL [ 22.2 nmol/L ] ) with no significant change in serum testosterone levels in matched , placebo-treated men . However , median prostate tissue levels of testosterone ( 0.91 ng/g ) and dihydrotestosterone ( 6.79 ng/g ) did not change significantly in the TRT group . No treatment-related change was observed in prostate histology , tissue biomarkers ( and rogen receptor , Ki-67 , CD34 ) , gene expression ( including AR , PSA , PAP2A , VEGF , NXK3 , CLU [ Clusterin ] ) , or cancer incidence or severity . Treatment-related changes in prostate volume , serum prostate-specific antigen , voiding symptoms , and urinary flow were minor . CONCLUSIONS These preliminary data suggest that in aging men with late-onset hypogonadism , 6 months of TRT normalizes serum and rogen levels but appears to have little effect on prostate tissue and rogen levels and cellular functions . Establishment of prostate safety for large population s of older men undergoing longer duration of TRT requires further study . Trial Registration clinical trials.gov Identifier : NCT00161304 OBJECTIVE Men with type 2 diabetes are known to have a high prevalence of testosterone deficiency . No long-term data are available regarding testosterone and mortality in men with type 2 diabetes or any effect of testosterone replacement therapy ( TRT ) . We report a 6-year follow-up study to examine the effect of baseline testosterone and TRT on all-cause mortality in men with type 2 diabetes and low testosterone . RESEARCH DESIGN AND METHODS A total of 581 men with type 2 diabetes who had testosterone levels performed between 2002 and 2005 were followed up for a mean period of 5.81.3 S.D. years . mortality rates were compared between total testosterone 10.4nmol/l ( 300ng/dl ; n=343 ) and testosterone 10.4nmol/l ( n=238 ) . the effect of TRT ( as per normal clinical practise : 85.9 % testosterone gel and 14.1 % intramuscular testosterone undecanoate ) was assessed retrospectively within the low testosterone group . RESULTS Mortality was increased in the low testosterone group ( 17.2 % ) compared with the normal testosterone group ( 9 % ; P=0.003 ) when controlled for covariates . In the Cox regression model , multivariate-adjusted hazard ratio ( HR ) for decreased survival was 2.02 ( P=0.009 , 95 % CI 1.2 - 3.4 ) . TRT ( mean duration 41.6±20.7 months ; n=64 ) was associated with a reduced mortality of 8.4 % compared with 19.2 % ( P=0.002 ) in the untreated group ( n=174 ) . The multivariate-adjusted HR for decreased survival in the untreated group was 2.3 ( 95 % CI 1.3 - 3.9 , P=0.004 ) . CONCLUSIONS Low testosterone levels predict an increase in all-cause mortality during long-term follow-up . Testosterone replacement may improve survival in hypogonadal men with type 2 diabetes BACKGROUND There is increasing use of hormone replacement therapy ( HRT ) by post-menopausal women . Observational epidemiological studies have shown reductions in cardiovascular risk factors in  HRT users in the USA , but no r and omized controlled trials of HRT have been carried out in the primary practice setting . Previous studies of cardiovascular risk factors have shown a variety of responses according to type of progestagen and oral or topical administration . None has examined the effect of route using an identical progestagen . OBJECTIVES Our aim was to establish differences , if any , in alteration in cardiovascular risk factors with HRT in post-menopausal women according to route of administration of HRT , oral , transdermal and implant , using first oestrogen alone then oestrogen plus norethisterone , or testosterone for implant . METHODS Subjects were recruited by letter of invitation to women aged 50 - 65 years from lists in general practice s local to the Charing Cross Hospital Lipid Clinic in West London . Their menopausal status was confirmed and they were r and omized to one of three treatment groups or acted as controls . They attended for three visits ; at baseline , HRT was initiated as oestrogen alone , oral or transdermal . At the 3-month visit , HRT with the progestagen , norethisterone , was given cyclically , continuously or transdermally until the final visit at 6 months . A separate group of women from the menopause clinic at Chelsea and Westminster Hospital were studied on oestrogen implant then on implanted oestrogen and testosterone . The outcome measures studied were the separate effects of the four regimes as compared with controls on lipoproteins , glucose , insulin , fibrinogen , factor VII and E-selectin , together with weight , waist : hip ratio and blood pressure . RESULTS The continuous combined oestrogen-progestagen therapy had similar effects on cardiovascular risk factors as oestrogen with cyclical progestagen . All regimes lowered low-density lipoprotein cholesterol , the oral route being more potent than the parenteral ; the effect of transdermal HRT was similar to the implant . Lp(a ) was reduced only with the oral route . Reductions in factor VII and E-selectin were observed in both the oral and transdermal routes . There was no increase in body mass index , waist : hip ratio , blood pressure or glucose and insulin levels with any of the HRT regimes used . Systolic blood pressure was reduced with the transdermal route . CONCLUSIONS This study supports the evidence that oestrogen-progestagen HRT , both oral and transdermal , although attenuating some of the benefit of oestrogen alone on fibrinogen and high-density lipoprotein , significantly reduces cardiovascular risk factors , which should diminish post-menopausal risk of coronary disease BACKGROUND The Hypertension Optimal Treatment ( HOT ) Study has provided information about cardiovascular events in 18790 hypertensives , subjected to pronounced blood pressure ( BP ) lowering for a mean of 3.8 years . The HOT study data have subsequently been analysed after stratification of the patients according to global cardiovascular risk , and it has been found that , despite intensive blood pressure lowering in all risk strata , morbid event rates increased with increasing risk stratum . OBJECTIVES Previously analysed global risk strata were based on combinations of risk factors . The analyses presented here were intended to provide information on the relative role that the presence of each individual factor may have in increasing cardiovascular risk , despite good BP control . METHODS Risk ratios ( RR ) for patients with and those without a risk factor were calculated with 95 % confidence intervals ( CI ) using a Cox proportional hazard model , and adjusted for all variables except the one under examination . RESULTS For all risk factors considered and for all types of event , RR were always greater than 1 , indicating a greater risk in the presence , compared with that in the absence of each factor . The male gender was a statistically significant risk for cardiovascular ( CV ) events , CV and total mortality and particularly for myocardial infa rct ion ( MI ) ; age > or = 65 years for CV events , stroke , CV and particularly total mortality ; smoking for all events analysed , but particularly for total mortality ( twice higher in smokers than in non-smokers ) ; high serum cholesterol ( > 6.8 mmol/l ) for CV events , MI and CV mortality ; high serum creatinine ( > 155 micromol/l ) for CV events , stroke , CV and total mortality ; diabetes for CV events , stroke , total mortality and particularly CV mortality ; and ischaemic heart disease for all events analysed . Adjusted RR were often close to or greater than 2 . CONCLUSIONS Each of the risk factors considered was found to be an important cause of residual risk , despite good BP control . These findings emphasize the importance of addressing other correctable risk factors , e.g. smoking , hypercholesterolaemia and diabetes , as well as rigorous control of blood pressure , and of initiating antihypertensive therapy before cardiovascular and renal damage becomes manifest Excretion of albumin in the urine is highly variable , ranging from nondetectable quantities to milligrams of albumin and even grams of albumin . Microalbuminuria is defined as low levels of urinary albumin excretion of 30 to 300 mg/d . Microalbuminuria is highly prevalent ; in hypertensive and diabetic population s , its prevalence varies from 10 to 40 % . It is interesting that microalbuminuria also is found frequently in seemingly healthy individuals ( 5 to 7 % ) . The variable excretion of albumin in the urine is related to the risk for the individual to develop cardiovascular ( CV ) disease : Absence or very low levels of albuminuria is associated with low CV risk , whereas the CV risk increases markedly with increasing amount of albumin in the urine ( even within the now considered normal range ) . The predictive power of urinary albumin levels for CV risk is independent of other CV risk factors and not only is present in individual with diabetes and /or hypertension but also in healthy individuals . Treatments that lower albuminuria are associated with CV protection , as demonstrated in r and omized , controlled trials of patients with diabetes as well as in patients with hypertension . There is preliminary evidence that albuminuria lowering is CV protective in healthy individuals with an elevated albumin excretion rate . Differences between individuals in their level of albumin excretion are already observed at a very early age ( just after birth ) . In fact , the interindividual variability seems to be relatively constant in the first 5 decades of life , indicating that microalbuminuria is not necessarily a consequence of vascular damage at later age . Higher levels of urinary albumin seem to reflect the ordinary interindividual variability in ( renal and systemic ) endothelial function . Experimental data show that between strains and even within strains , rats at young age show a remarkable difference in individual endothelial function , and this is strongly related to the susceptibility of that rat to organ damage . In conclusion , albuminuria seems to be a sensitive marker very early in life for the susceptibility of an individual to CV disease . It therefore may be an ideal target for early primary prevention using CV-protective therapy regimens AIM Explore the relation between body mass index ( BMI ) and cardiovascular disease , and the influence of optimal medical therapy ( OMT ) on this relationship . METHODS AND RESULTS Patients from the REACH cohort , an international , prospect i ve cohort of patients with or at high risk of atherosclerosis with documentation of potential confounders , including treatments and risk factors , were followed up to 4 years ( n = 54 285 ) . Patients were categorized according to baseline BMI ( ranging from underweight to Grade III obesity ) . Optimal medical therapy was defined as the use of the four cardioprotective medication classes ( statins , ACE inhibitors/angiotensin II receptor blockers , β-blockers , and antiplatelet agents ) . The main outcomes were all-cause mortality , cardiovascular ( CV ) mortality , and CV events . In primary and secondary prevention , a reverse J-shaped curve best described the relationship between BMI categories and the incidence of the various outcomes . In secondary prevention , the highest adjusted risks were observed for underweight patients ( 1.97 , P < 0.01 , and 1.29 , P = 0.03 , for CV mortality and CV events ) and the lowest HRs were observed , respectively , in Grade II and Grade III obese patients ( 0.73 , P < 0.01 and 0.80 , P < 0.01 ) . The proportion of patients on OMT increased with BMI from 10.1 to 36 % ( P < 0.001 ) . The apparent CV protection conferred by obesity persisted in patients receiving OMT . CONCLUSION An obesity paradox was observed in both primary and secondary CV prevention patients . The intensity of use of evidence -based preventive medications does not account for the paradoxical CV protection associated with obesity . At extremes of BMI , further interventions beyond OMT may be needed to reduce CV risk Background Women with polycystic ovary syndrome ( PCOS ) are at increased risk for cardiovascular ( CV ) and metabolic disorders . There is a close relationship between elevated and rogen plasma levels and the ultrasound findings of stromal hypertrophy . In r and omized trials , the administration of metformin has been shown to be followed by an improvement in insulin sensitivity and decrease in and rogen levels in most women . In the present study , we investigate the association between reduced ovarian volume in PCOS patients after administration of metformin with improvement in CV risk factors . Material s and Methods This was a r and omized clinical trial study . A total of 28 women diagnosed with PCOS who referred to the infertility clinic were selected .  Anthropometric characteristics of the patients , mean ovarian volume and plasma levels of fasting blood sugar ( FBS ) , lipid profile , luteinizing hormone ( LH ) , follicle stimulating hormone ( FSH ) , estradiol , testosterone , 17-α-OH progesterone ( 17OHP ) , dehydroepi and rosterone sulfate ( DHEAS ) , C-reactive protein ( CRP ) and homocysteine ( Hcy ) were evaluated before and after treatment with 500 mg metformin , three times daily for three months . Statistics were calculated with the aid of SPSS 16.0 with student ’s paired t- and Pearson ’s correlation coefficient tests . Significance was set at p<0.05 . Results There were significant reductions in mean ovarian volume and body mass index ( BMI ) , in addition to CRP , Hcy , testosterone , FBS , HDL and LDL levels . There was a positive correlation between mean ovarian volume and waist-to-hip ratio (WHR).After treatment , there correlation noted with reduction in mean ovarian volume and decreased BMI , in addition to reductions in CRP , LDL , Hcy and testosterone levels . Conclusion A positive correlation may exist between reduced mean ovarian volume and improvement in CV risk factors  after administration of metformin ( Registeration Number : I RCT 138903244176N1 ) During the perioperative period cardiac surgical patients are often monitored by pulmonary artery ( PA ) catheters . This catheter , which is floated through the right heart into the pulmonary artery , enables the intensivist to measure and calculate indices of myocardial performance . After a variable period of time this invasive monitoring can often be ab and oned following cardiovascular stabilization in these patients , but patients usually still require a central venous ( CV ) access for diagnostic and therapeutic purpose s. To place this CV catheter either a de novo puncture at a new site or a guide-wire change at the existing exit site through the PA catheter in place can be performed . Each de novo puncture is associated with a risk of traumatising internal vessels or organs . In contrast , guide-wire change avoids this risk but inherits a potential risk of transferring bacteria by manipulation of contaminated lines . Our study included 159 consecutive cardiac surgical patients in whom PA monitoring was established preoperatively and terminated within a period of up to 72 hours postoperatively . At r and om the PA catheter was replaced by a CV line either by de novo puncture or by guide-wire change . All CV lines were left in place for 7 days according to st and ard practice in our intensive care unit ( ICU ) . After removal of CV catheters all catheter tips were cultured semiquantitatively by rollplate technique according to Maki ( 26 ) and subsequent immersion broth culture . A positive culture was defined as growth of one up to 15 colonies on the agar-plate or any microbial growth in the broth . A significant colonization was assumed in catheters yielding more than 15 colony forming units ( cfu ) on the blood agar plate ( 26 ) . Our results show a significant risk of colonization and catheter-related infection associated with the guide-wire technique as opposed to the de novo puncture . The figures for relevant colonization were 33.3 % in the guide-wire group as opposed to 10.5 % in the de novo group . However , this difference was noted only in the subgroup in which replacement of PA catheters by CV catheters was performed beyond 48 h after initial insertion of PA catheters . Within the time intervals of 24 and 25 to 48 h , respectively , we could not detect any significant difference between groups Background Evidence concerning the importance of glucose lowering in the prevention of cardiovascular ( CV ) outcomes remains controversial . Given the multi-faceted pathogenesis of atherosclerosis in diabetes , it is likely that any intervention to mitigate this risk must address CV risk factors beyond glycemia alone . The SGLT-2 inhibitor empagliflozin improves glucose control , body weight and blood pressure when used as monotherapy or add-on to other antihyperglycemic agents in patients with type 2 diabetes . The aim of the ongoing EMPA-REG OUTCOME ™ trial is to determine the long-term CV safety of empagliflozin , as well as investigating potential benefits on macro-/microvascular outcomes . Methods Patients who were drug-naïve ( HbA1c ≥7.0 % and ≤9.0 % ) , or on background glucose-lowering therapy ( HbA1c ≥7.0 % and ≤10.0 % ) , and were at high risk of CV events , were r and omized ( 1:1:1 ) and treated with empagliflozin 10 mg , empagliflozin 25 mg , or placebo ( double blind , double dummy ) superimposed upon the st and ard of care . The primary outcome is time to first occurrence of CV death , non-fatal myocardial infa rct ion , or non-fatal stroke . CV events will be prospect ively adjudicated by an independent Clinical Events Committee . The trial will continue until ≥691 confirmed primary outcome events have occurred , providing a power of 90 % to yield an upper limit of the adjusted 95 % CI for a hazard ratio of < 1.3 with a one-sided α of 0.025 , assuming equal risks between placebo and empagliflozin ( both doses pooled ) . Hierarchical testing for superiority will follow for the primary outcome and key secondary outcomes ( time to first occurrence of CV death , non-fatal myocardial infa rct ion , non-fatal stroke or hospitalization for unstable angina pectoris ) where non-inferiority is achieved . Results Between Sept 2010 and April 2013 , 592 clinical sites r and omized and treated 7034 patients ( 41 % from Europe , 20 % from North America , and 19 % from Asia ) . At baseline , the mean age was 63 ± 9 years , BMI 30.6 ± 5.3 kg/m2 , HbA1c 8.1 ± 0.8 % , and eGFR 74 ± 21 ml/min/1.73 m2 . The study is expected to report in 2015 . Discussion EMPA-REG OUTCOME ™ will determine the CV safety of empagliflozin in a cohort of patients with type 2 diabetes and high CV risk , with the potential to show cardioprotection . Trial registration Clinical trials.gov Severe upper limb paresis is a major contributor to disability after stroke . This study investigated the efficacy of task-related training ( TRT ) with transcutaneous electrical nerve stimulation ( TENS ) on recovery of upper limb motor function in chronic-stroke survivors . Thirty patients with chronic stroke were r and omly allocated two groups : the TRT+TENS group ( n = 15 ) and the TRT+placebo ( TRT+PLBO ) group ( n = 15 ) . Patients in the TRT+TENS group received TENS stimulation ( two to three times the sensory threshold ) , while subjects in the TRT+PLBO group received TENS without real electrical stimulation . TENS was applied to muscle belly of triceps and wrist extensors , while placebo ( PLBO ) stimulation was administrated without real electrical stimulation . Both interventions were given for 30 minutes per day , 5 days per week , for a period of 4 weeks . The primary outcomes were assessed with Fugl-Meyer assessment scores ( FMA ) , Manual function test ( MFT ) , Box and block test ( BBT ) , and Modified Ashworth scale ( MAS ) , each of which was performed one day before and one day after intervention . Both groups showed significant improvements in FMA , MFT , and BBT after intervention . When compared with the TRT+PLBO group , the TRT+TENS group showed significantly greater improvements in FMA ( p = 0.034 ) , MFT ( p = 0.037 ) , and BBT ( p = 0.042 ) . In MAS score , significant improvement was observed only in the TRT+TENS group ( p = 0.011 ) . Our findings indicate that TRT with TENS can reduce motor impairment and improve motor activity in stroke survivors with chronic upper limb paresis , highlighting the benefits of somatosensory stimulation from TENS Objective - A lack of global cardiovascular ( CV ) risk approach is often observed in the clinical practice . Having conceived a clinical strategy aim ed at helping general practitioners ( GPs ) to assess and manage global CV risk in the daily practice , we wanted to evaluate the impact of a training promoting this strategy . Methods - R and omised controlled trial involving GPs registered in a continual medical education ( CME ) group . The intervention and control arms included 7 ( 123 GPs ) and 13 ( 220 GPs ) groups , respectively . The intervention was a training in CV prevention provided during a CME meeting . GPs answered a question naire four months after the training . The main outcome was the use of a global CV risk assessment tool . Secondary outcomes were the GPs ’ awareness of the CV diseases burden , knowledge of the CV risk factors , and CV therapeutic attitudes . Results - More trained GPs ( 76 % vs. 52 % ) used a global CV risk assessment tool ( p??=??0.003 ) . Significant differences were also observed for secondary outcomes : ( a ) awareness of CV diseases burden : more trained GPs were aware of the lethality from myocardial infa rct ion ( 37 % vs. 21 % , p??=??0.047 ) and considered it as the main cause of sudden death in adults ( 78 % vs. 59 % , p??=??0.018 ) ; ( b ) knowledge of risk factors : more trained GPs considered familial CV history ( 89 % vs. 73 % , p??=??0.021 ) and HDL-cholesterol ( 82 % vs.62 % , p??=??0.013 ) as important CV risk factors ; ( c ) therapeutic attitudes : fewer trained GPs used to prescribe a lipid-lowering drug based on a total cholesterol value without considering the other risk factors ( 44 % vs.65 % , p??=??0.013 ) . Conclusions - The global CV risk approach in the general practice was favourably influenced by this training provided during a CME meeting . The impact of the training on patients ’ outcomes should be addressed in a prospect i ve trial The primary purpose of this investigation was to determine the impact of altering the set structure during an 8-week resistance training program on anthropometric , hormonal , and strength power characteristics . Thirty female volleyball players were recruited for participation and then r and omly assigned to 1 of 3 resistance training groups : ( i ) cluster sets ( CRT ; n = 10 ) , ( ii ) traditional sets ( TRT ; n = 10 ) , or ( iii ) control ( CON ; n = 10 ) . All athletes were evaluated for thigh and arm circumference , vertical jump , 20-m sprint , 4 × 9-m shuttle-run , 1-repetition maximum ( 1RM ) back squat , bench press , military press , and deadlift prior to and after an 8-week periodized training intervention . Blood sample s were taken before and after the 8-week training period to evaluate resting testosterone , cortisol , and insulin-like growth factor 1 responses to the training period . After 8 weeks of training the CRT group displayed a small but significant improvement in vertical jump ( CRT : effect size ( ES ) = 038 , 7.1 % ) performance when compared with the TRT group ( ES = 0.34 , 5.6 % ) . Both the CRT and TRT training interventions result ed in very large increases in the 1RM squat ( CRT : 8.4 % ± 1.2 % ; TRT : 7.3 % ± 0.6 % ) , bench press ( CRT : 8.3 % ± 2.0 % ; TRT : 8.7 % ± 1.9 % ) , military press ( CRT : 5.7 % ± 1.2 % ; TRT : 5.5 % ± 1.6 % ) , and deadlift ( CRT : 8.2 % ± 1.6 % ; TRT : 8.3 % ± 2.2 % ) . There were no significant differences in 20-m sprint or 4 × 9-m shuttle run times between the CRT , TRT , and CON groups . These results suggest that cluster sets allow for greater improvements in vertical jump performance and equal improvements in strength gains to those seen with traditional sets Two hundred fourteen eligible patients with previously untreated , localized Ewing 's sarcoma of bone were r and omized on IESS-II to receive Adriamycin ( ADR ; doxorubicin ; Adria Laboratories , Columbus , OH ) , cyclophosphamide , vincristine , and dactinomycin by either a high-dose intermittent method ( treatment [ trt ] 1 ) or a moderate-dose continuous method ( trt 2 ) similar to the four-drug arm of IESS-I. Patient characteristics ( sex , primary site , type of surgery ) were stratified at the time of registration ; these and other patient characteristics ( age , time from symptoms to diagnosis , race ) were distributed similarly between treatments . Surgical resection was encouraged , but not m and atory . Local radiation therapy was the same as for IESS-I. The median follow-up time is 5.6 years . The overall outcome was significantly better on trt 1 than on trt 2 . At 5 years , the estimated percentages of patients who were disease-free , relapse-free , and surviving were 68 % , 73 % , and 77 % for trt 1 and 48 % , 56 % , and 63 % for trt 2 ( P = .02 , .03 , and .05 , respectively ) . The major reason for treatment failure for both treatment groups was the development of metastatic disease . The lung was the most common site of metastases followed by bone sites . The combined incidence of severe or worse toxicity ( 67 % ) was comparable between the treatments ; however , severe or worse cardiovascular toxicity was significantly greater on trt 1 . Tne only treatment-associated deaths ( N = 3 ) were on trt 1 and were cardiac-related OBJECTIVES Assess the risk of ischaemic events associated with psychosocial stress in patients with stable coronary heart disease ( CHD ) . METHODS Psychosocial stress was assessed by a question naire  in 14 577 patients ( median age 65.0 , IQR 59 , 71 ; 81.6 % males ) with stable CHD on optimal secondary preventive therapy in the prospect i ve r and omized STABILITY clinical trial . Adjusted Cox regression models were used to assess associations between individual stressors , baseline cardiovascular risk factors and outcomes . RESULTS After 3.7 years of follow-up , depressive symptoms , loss of interest and financial stress were associated with increased risk ( hazard ratio , 95 % confidence interval ) of CV death ( 1.21 , 1.09 - 1.34 ; 1.15 , 1.05 - 1.27 ; and 1.19 , 1.08 - 1.30 , respectively ) and the primary composite end-point of CV death , nonfatal MI or nonfatal stroke ( 1.21 , 1.13 - 1.30 ; 1.19 , 1.11 - 1.27 ; and 1.17 , 1.10 - 1.24 , respectively ) . Living alone was related to higher risk of CV death ( 1.68 , 1.38 - 2.05 ) and the primary composite end-point ( 1.28 , 1.11 - 1.48 ) , whereas being married as compared with being widowed , was associated with lower risk of CV death ( 0.64 , 0.49 - 0.82 ) and the primary composite end-point ( 0.81 , 0.67 - 0.97 ) . CONCLUSIONS Psychosocial stress , such as depressive symptoms , loss of interest , living alone and financial stress , were associated with increased CV mortality in patients with stable CHD despite optimal medical secondary prevention treatment . Secondary prevention of CHD should therefore focus also on psychosocial issues both in clinical management and in future clinical trials Cardiovascular disease is more common in patients with chronic kidney disease ( CKD ) , and traditional risk factors do not adequately predict those at risk for cardiovascular ( CV ) events . Recent evidence suggests elevated  trimethylamine N-oxide ( TMAO )  , created by gut microflora from dietary L-carnitine and choline , is associated with CV events . We investigated the relationship of TMAO levels in patients with stages 3b and 4 CKD to ischemic CV events using the CanPREDDICT cohort , a Canada-wide observational study with prospect i ve 3-year follow-up of adjudicated CV events . Baseline sample s were obtained for 2529 CKD patients .  TMAO , choline , and L-carnitine levels  were measured using t and em mass spectrometry . Baseline median TMAO level was high for the whole cohort ( 20.41 μM ; interquartile range [ IQR ] : 12.82 - 32.70 μM ) . TMAO was independently associated with CV events ( hazard ratio 1.23 ; 95 % confidence interval : 1.06 - 1.42 / 1 SD lnTMAO ) after adjusting for all potential CV risk factors . Those in the highest TMAO quartile had significantly higher risk of CV events ( adjusted hazard ratio 1.59 ; 95 % confidence interval : 1.04 - 2.43 ; P = 0.0351 ) in the analysis of recurring ischemic events . Among those with stage 3b CKD ( hazard ratio 1.45 ; 95 % confidence interval : 1.12 - 1.87 / 1 SD lnTMAO ) , independent of kidney function , TMAO levels identified those at highest risk for events . Our results suggest that TMAO may represent a new potentially modifiable CV risk factor for CKD patients . Further studies are needed to determine sources of variability and if lowering of TMAO reduces CV risk in CKD Background —Influenza infection has been associated with increased risk of adverse cardiac and cerebral vascular outcomes .  Oseltamivir , a treatment for influenza , has been shown to decrease the severity of an influenza episode , but few data exist regarding its potentially protective effect against recurrent vascular outcomes among influenza patients with a history of vascular disease . Methods and Results —Electronic healthcare service and pharmacy records for 37 482 TRICARE beneficiaries , aged 18 and older , with a coded history of cardiovascular ( CV ) disease and a subsequent diagnosis of influenza from October 1 , 2003 , through September 30 , 2007 , were examined . Subjects were grouped according to whether they had filled a prescription for oseltamivir within 2 days of their influenza diagnosis . The incidence of recurrent CV events within 30 days after the influenza diagnosis among oseltavmivir-treated and untreated subjects was 8.5 % and 21.2 % , respectively ( P<0.005 ) . Subject age was a persistent and significant contributor to the likelihood of recurrent CV outcomes . After controlling for the differences in demographics among treated and untreated cohorts using a propensity-scored logistic regression model , a statistically significant protective effect was associated with oseltamivir treatment ( odds ratio , 0.417 ; 95 % CI , 0.349 to 0.498 ) . Conclusions —Our findings suggests that oseltamivir treatment for influenza is associated with significant decrease in the risk of recurrent CV events in subjects with a history of CV disease . These findings merit confirmation in further prospect i ve and controlled studies . Meanwhile , in patients with CV disease , strict adherence with current practice guidelines for prevention and treatment of influenza is recommended OBJECTIVE : To demonstrate the efficacy of tinnitus retraining therapy ( TRT ) for tinnitus relief compared to a waiting list group and a partially treated group ( patients that refused prosthesis adaptation )  . STUDY DESIGN : Prospect i ve non-r and omised clinical assay ( n = 158 ) .  Visual analogue scale ( VAS ) for intensity and the Tinnitus H and icap Inventory ( THI ) were evaluated at 12-month period . RESULTS : Eighty two percent of the patients that followed TRT  improved their tinnitus according to their self-evaluation . THI score was reduced from 48 % to 32 % and VAS decreased from 6.6 to 5.3 after one year ( p < 0.05 ) . TRT patients showed a higher improvement on their tinnitus , THI and VAS scores when compared with the waiting list patients and with patients that refused prosthesis adaptation when recommended ( p < 0.05 ) . CONCLUSIONS : TRT improved tinnitus in 82 % of the subjects and statistically reduced THI and VAS scores after 12 months . TRT has shown to be more effective than a waiting list group and partially treated patients Vitamin D recently has been proposed to play an important role in a broad range of organ functions , including cardiovascular ( CV ) health ; however , the CV evidence -base is limited . We prospect ively analyzed a large electronic medical records data base to determine the prevalence of vitamin D deficiency and the relation of vitamin D levels to prevalent and incident CV risk factors and diseases , including mortality . The data base contained 41,504 patient records with at least one measured vitamin D level . The prevalence of vitamin D deficiency ( ≤30 ng/ml ) was 63.6 % , with only minor differences by gender or age . Vitamin D deficiency was associated with highly significant ( p < 0.0001 ) increases in the prevalence of diabetes , hypertension , hyperlipidemia , and peripheral vascular disease . Also , those without risk factors but with severe deficiency had an increased likelihood of developing diabetes , hypertension , and hyperlipidemia . The vitamin D levels were also highly associated with coronary artery disease , myocardial infa rct ion , heart failure , and stroke ( all p < 0.0001 ) , as well as with incident death , heart failure , coronary artery disease/myocardial infa rct ion ( all p < 0.0001 ) , stroke ( p = 0.003 ) , and their composite ( p < 0.0001 ) . In conclusion , we have confirmed a high prevalence of  vitamin D deficiency in the general healthcare population and an association between vitamin D levels and prevalent and incident CV risk factors and outcomes . These observations lend strong support to the hypothesis that vitamin D might play a primary role in CV risk factors and disease . Given the ease of vitamin D measurement and replacement , prospect i ve studies of vitamin D supplementation to prevent and treat CV disease are urgently needed 190 Background : GnRH agonists have been associated with a greater incidence of  CV events  in men with prostate cancer . Less is known about GnRH antagonists and CVD . We used prospect i ve data to evaluate the relationships of baseline CV risk , dosing regimen and duration of degarelix therapy , and CV events . METHODS Data from 16 phase II/III and one extended phase III trial was pooled ( n=1,704 ) . Maintenance doses and exposure time varied between 20 - 480 mg and 1 - 66 months , respectively . Baseline CV risk was assessed based on established CVD , BMI ( > 30 kg/m2 ) , smoking , hypertension , type 2 diabetes , and hyperlipidemia . Patients were stratified into 3 groups : 1 ) no CV risk factors ( n=337 ) , 2 ) ≥1 CV risk factors without CVD ( n=803 ) , 3 ) established CVD ( n=564 ) . Acute CV events were collected prospect ively . RESULTS The incidence of CV events in patients with established CVD , ≥1 CV risk factors , and no CV risk factors was 20 % ( n=112 ) , 8 % ( n=57 ) and 7 % ( n=28 ) , respectively . Established CVD was associated with a 3.1-fold increased risk for CV events ( p<0.0001 ) , whereas presence of ≥1 CV risk factors with 1.3-fold ( p=0.28 ) . The cumulative hazard curve indicated no increases in hazards with increasing duration of treatment . Hazards of primary CV events  during degarelix treatment ( 0.049 ) were not statistically different from that during the 2 years prior treatment ( 0.48 , p=0.85 ) . In multivariate models , age , established CV disease , high BMI and no alcohol consumption were independently associated with greater risk for CV events ( Table ) ; type 2 diabetes ( p=0.13 ) and smoking ( p=0.08 ) were of borderline significance . Degarelix dose and schedule were not associated with CV risk ( p=0.78 ) in the model . CONCLUSIONS CV events during degarelix treatment were largely confined to those with established CVD and further modulated by aging and modifiable risk factors . Rates of CV events were similar before and after degarelix treatment . [ Table : see text ] [ Table : see text ] BACKGROUND Patients with chronic kidney disease are at increased risk for cardiovascular ( CV ) events . METHODS We r and omly assigned 1,094 African Americans with hypertensive nephrosclerosis ( glomerular filtration rate [ GFR ] , 20 to 65 mL/min/1.73 m(2 ) [ 0.33 to 1.08 mL/s ] ) to initial antihypertensive treatment with either : ( 1 ) a beta-blocker , metoprolol ; ( 2 ) an angiotensin-converting enzyme inhibitor , ramipril ; or ( 3 ) a dihydropyridine calcium channel blocker , amlodipine , and either a usual-blood pressure ( BP ) or low-BP treatment goal . Using a design powered to detect renal outcome differences , we compared the effect of treatment on the CV event rate ( cardiac death , myocardial infa rct ion , stroke , and heart failure ) during a mean follow-up period of 4.1 years and determined baseline factors that predict CV outcomes . RESULTS Thirty-one patients died of CV disease ( 0.7%/patient-year ) , and 149 patients experienced at least 1 CV outcome ( 3.3%/patient-year ) . Overall , 202 CV events ( 4.5%/patient-year ) occurred . The CV outcome rate was not related significantly to r and omized interventions . In multivariable analyses , 7 baseline risk factors remained independently associated with increased risk for the CV composite outcome after controlling for age , sex , baseline GFR , and baseline proteinuria group : pulse pressure , duration of hypertension , abnormal electrocardiogram result , non-high-density lipoprotein cholesterol level , serum urea nitrogen level , urine protein-creatinine ratio , urine sodium-potassium ratio , and annual income less than 15,000 dollars . CONCLUSION Neither r and omized class of antihypertensive therapy nor BP level had a significant effect on the occurrence of CV events , possibly because of limited power . However , this analysis identifies unique and potentially modifiable CV risk factors in this high-risk cohort This 1-year , group-r and omized , intervention-control study looked at the effectiveness of a primary prevention , community-based program for reducing  cardiovascular ( CV ) risk factors in women . Women between the ages of 20 and 50 were recruited through community contacts , including religious and academic institutions , health clinics , and large local employers in the Duluth , Minnesota , and Superior , Wisconsin , area . All study activities took place in neighborhood places of worship . Screenings at baseline and 12 months included physical and laboratory measurements  addressing  CV risk factors  and assessment of the women 's knowledge about CV disease in women . All participants received an individualized review of their CV risk factors and recommendations for modifying them , along with educational literature about CV disease in women . The control group had limited follow-up compared with the intervention group , who participated in general CV health classes and received a follow-up phone call and information about health re sources . The study showed that education and one-on-one follow-up significantly change behavior . Comprehensive community-based screening and individualized review decrease women 's risk for CV disease BACKGROUND Accelerated atherosclerosis result ing in an abnormally high incidence of coronary and cerebrovascular occlusive accidents has been repeatedly reported in dialysis patients , but incidence and risk factors of such complications in chronic renal failure ( CRF ) predialysis patients are debated . METHODS We prospect ively assessed the incidence of first myocardial and cerebral infa rct ion episodes in a cohort of 147 CRF patients ( 99 male ) followed from January 1985 to December 1994 . Relevant clinical and laboratory risk factors for atherogenesis were determined at yearly intervals . They included blood pressure , smoking , blood lipids , fibrinogen , and homocysteine  which were compared in patients with ( CVA+ ) or without ( CVA- ) occurrence of cardiovascular ( CV ) atherosclerotic accidents . RESULTS Incidence of CV accidents was nearly three times higher in CRF patients than in the French general population in both genders . In particular , incidence of myocardial infa rct ion in male patients aged 45 - 55 , 55 - 65 and > 65 years was 7.6 , 18.2 , and 27.8/1000 patient-years , respectively , compared to 3.4 , 8.9 , and 10.4/1000 subject-years in the general population . Although age and degree of renal failure at onset of CV events or at end of follow-up did not differ between CVA+ and CVA- groups , cigarette smoking ( 24.5 [ SD 24.3 ] vs 8.2 [ 14.7 ] pack-years , P < 0.0001 ) and systolic blood pressure ( 159 [ 19 ] vs 148 [ 19 ] mmHg , P < 0.001 ) were markedly higher in CVA+ patients . Similarly , mean plasma HDL-cholesterol was lower , whereas LDL-cholesterol , triglycerides , apoB , Lp(a ) , fibrinogen , and homocysteine levels all were significantly higher in CVA+ than in CVA- patients . Multivariate Cox analysis identified cigarette smoking , systolic pressure , HDL cholesterol , and fibrinogen as independent risk factors for developing CV accidents . CONCLUSIONS Incidence of atherosclerotic CV complications is abnormally high in predialysis CRF patients , suggesting that the uraemic state per se is associated with atherogenesis . As several of the identified clinical and metabolic risk factors for such accidents are potentially remediable by specific therapeutic interventions , prophylactic measures should be initiated long before start of renal replacement therapy Background The optimal intensity and duration of the intervention to achieve sustained risk reduction in patients at high and very high cardiovascular ( CV ) risk still need to be established . The aim of this study was to evaluate the impact of general practitioner ’s ( GP ’s ) systematic and planned intervention on total CV risk reduction and a change in individual CV risk factors . Material / Methods This was a cluster-r and omized trial ( IS RCT N31857696 ) including 64 practice s and 3245 patients aged ≥40 . The participating GPs and their examinees were r and omized into an intervention or to a control group ( st and ard care ) . Intervention group practitioners followed up their examinees during 1 , 3 , 6 , 12 , and 18 months . The main outcome measures were change in proportion of patients with low , moderate , high , and very high CV risk , and change in individual CV risk factors from the first to the second registration . Results The proportion of patients with very high CV risk was lower in the intervention group , the same as of patients with high blood pressure , total and LDL cholesterol , and increased intake of alcohol . The mean systolic ( −1.49 mmHg ) and diastolic ( −1.57 mmHg ) blood pressure , triglycerides ( −0.18 mmol/L ) , body mass index ( −0.22 ) , and waist ( −0.4 cm ) and hip circumference ( −1.08 cm ) was reduced significantly in the intervention group . There was no additional impact in the intervention group of other tested CV risk factors . Conclusions Systematic and planned GP ’s intervention in CVD prevention reduces the number of patients with very high total CV risk and influences a change in lifestyle habits Background : Dapagliflozin is a sodium‐glucose co‐transporter‐2 ( SGLT‐2 ) inhibitor that reduces blood glucose in patients with type 2 diabetes mellitus ( T2DM ) by promoting glycosuria via inhibiting urinary glucose reabsorption . In addition to improving blood glucose control , treatment with dapagliflozin results in glucose‐induced osmotic diuresis , weight loss , and blood pressure lowering . Previous trials of SGLT‐2 inhibitors showed reductions in cardiovascular ( CV ) events , including CV death and hospitalization for heart failure , and ischemic events in patients with atherosclerotic cardiovascular disease ( ASCVD ) . Research design and methods : DECLARE – TIMI 58 ( NCT01730534 ) is a phase 3b r and omized , double‐blind , placebo‐controlled trial design ed to evaluate the CV safety and efficacy of dapagliflozin that has completed r and omization of 17,160 patients with T2DM and a history of either established ASCVD ( n = 6,971 ) or multiple risk factors for ASCVD ( n = 10,189 ) . Patients were r and omized in a 1:1 fashion to dapagliflozin 10 mg or matching placebo . The primary safety outcome is the time to the first event of the composite of CV death , myocardial infa rct ion , or ischemic stroke ( major adverse cardiovascular events ; MACEs ) . The co‐ primary efficacy outcomes are the composite of CV death , myocardial infa rct ion , or ischemic stroke and the composite of CV death or hospitalization for heart failure . This event‐driven trial will continue until at least 1,390 subjects have a MACE outcome , thereby providing > 99 % power to test for the primary outcome of safety  of dapagliflozin measured by rejecting the hypothesis that the upper bound of the CI > 1.3 for the primary outcome of MACE , as well as 85 % power to detect a 15 % relative risk reduction in MACE and an estimated 87 % power to detect a 20 % reduction in the composite of CV death or hospitalization for heart failure at a 1‐sided & agr ; level of .0231 . Conclusion : The DECLARE – TIMI 58 trial is testing the hypotheses that dapagliflozin is safe ( does not increase ) and may reduce the occurrence of major CV events . DECLARE – TIMI 58 is the largest study to address this question with an SGLT‐2 inhibitor in patients with T2DM and with established CV disease and without CV disease but with multiple risk factors OBJECTIVES To investigate whether the CHADS2 and CHA2DS2-VASc scores have clinical utility for prediction of adverse vascular function and vascular dysfunction-mediated incident cardiovascular ( CV ) events among high-risk patients without atrial fibrillation ( AF ) , and the additional value of incorporating PR prolongation to the scores . METHODS We analyzed 579 high-risk CV out patients without clinical AF in a prospect i ve cohort for new-onset ischemic stroke , myocardial infa rct ion ( MI ) , congestive heart failure ( CHF ) , and CV death .  Brachial flow-mediated dilation ( FMD ) and nitroglycerin-mediated dilatation ( NMD ) , carotid intima-media thickness ( IMT ) and pulse wave velocity ( PWV ) were determined . RESULTS Baseline CHADS2 score was associated with lower FMD ( Pearson r = -0.16 , P < 0.001 ) and NMD ( r = -0.17 , P < 0.001 ) , higher carotid IMT ( r = 0.30 , P < 0.001 ) and PWV ( r = 0.35 , P < 0.001 ; similar for CHA2DS2-VASc score : All P < 0.05 ) . After follow-up of 63 ± 11 months , 82 patients ( 14.2 % ) developed combined CV endpoint . ROC curve analysis showed that both CHADS2 and CHA2DS2-VASc scores were predictors for ischemic stroke ( C-Statistic : CHADS2 0.70 , P = 0.004 ; CHA2DS2-VASc 0.68 , P = 0.010 ) , MI ( CHADS2 0.63 , P = 0.030 ; CHA2DS2-VASc 0.70 , P = 0.001 ) , and CV death ( CHADS2 0.63 , P = 0.022 ; CHA2DS2-VASc 0.65 , P = 0.011 ) . Higher CHADS2 score was associated with reduced event-free survival from combined CV endpoints ( log-rank = 16.7 , P < 0.001 ) with differences potentiated if stratified by CHA2DS2-VASc score ( log-rank = 29.2 , P < 0.001 ) . Incorporating PR prolongation , the CHA2DS2-VASc-PR score achieved the highest C-Statistic for CV death prediction ( 0.70 , P < 0.001 ) superior to the CHADS2 score ( chi-square : 12.1 , P = 0.0005 ) . CONCLUSIONS The CHADS2 and CHA2DS2-VASc predict vascular dysfunction and cardiovascular events in high-risk CV patients without clinical AF , with further improved performance incorporating PR prolongation Abstract Objective : The objective was to assess the relative risk ( RR ) for cardiovascular ( CV ) events across all 8 r and omized phase 2/3 trials evaluating saxagliptin in patients with type 2 diabetes mellitus . Methods : Cardiovascular events ( death , myocardial infa rct ion [ MI ] , stroke , revascularization procedures , and cardiac ischemia ) were reported by investigators through st and ard adverse event reporting procedures and were systematic ally identified . Post hoc blinded adjudication of all deaths , MIs , and strokes was performed using prespecified endpoint definitions by an independent clinical events committee ( CEC ) . Results : A total of 4607 r and omized and treated patients ( n = 3356 treated with saxagliptin [ 2.5–100 mg/d ] ; n = 1251 , comparator [ n = 656 , placebo ; n = 328 , metformin ; n = 267 , uptitrated glyburide ] ) were included . The median ages were 54 years ( saxagliptin ) and 55 years ( comparator ) ( interquartile range , 47–61 each ) ; 51 % were female , 73 % were white , 52 % were hypertensive , 44 % had hypercholesterolemia , 39 % had a smoking history , 20 % had a first-degree family member with premature coronary heart disease , and 12 % had prior CV disease . Cardiovascular events were experienced by 61 patients ( 38 [ 1.1 % ] , saxagliptin ; 23 [ 1.8 % ] , comparator ) , and CV death/MI/stroke events were reported by investigators in 41 patients : 23 ( 0.7 % ) , saxagliptin ; 18 ( 1.4 % ) , comparator ( relative risk , 95 % confidence interval [ CI ] , 0.44 [ 0.24–0.82 ] ) . The CEC review ed 147 patients with potential CV events and identified a total of 40 patients with CV death/MI/stroke : 22 ( 0.7 % ) , saxagliptin ; 18 ( 1.4 % ) , comparator ( RR , 0.43 [ 0.23–0.80 ] ) . Component proportions for CV death , MI , and stroke were ( saxagliptin vs comparator ) : 7 ( 0.2 % ) vs 10 ( 0.8 % ) , 8 ( 0.2 % ) vs 8 ( 0.6 % ) , and 11 ( 0.3 % ) vs 5 ( 0.4 % ) , respectively . Conclusion : No increased risk of CV death/MI/stroke was observed in patients r and omly assigned saxagliptin across a broad drug development program . Although this systematic overview has inherent and important limitations , the data support a potential reduction in CV events with saxagliptin . The hypothesis of CV protection with saxagliptin will be tested prospect ively in a large r and omized clinical outcome trial evaluating saxagliptin compared with st and ard of care in patients with type 2 diabetes at increased risk for CV events BACKGROUND Studies linking low serum testosterone concentration to adverse clinical outcomes in hemodialysis patients have been relatively small . We investigated the role of testosterone in adverse outcomes and quality of life in an incident cohort of male Canadian hemodialysis patients . STUDY DESIGN A prospect ively design ed multicenter observational study using data from the Canadian Kidney Disease Cohort Study ( CKDCS ) . SETTING & PARTICIPANTS Male patients initiating hemodialysis therapy since February 14 , 2005 , in 3 Canadian centers serving ethnically diverse population s were studied ( N = 623 ) . PREDICTOR Serum  testosterone levels using the International Society of And rology , International Society for the Study of the Aging Male , and European Association of Urology cutoffs ( low , < 231 ng/dL ; borderline , 231 - 346 ng/dL ; normal , > 346 ng/dL ) . OUTCOMES All-cause mortality , fatal and nonfatal cardiovascular ( CV ) events , and Health Utility Index (HUI)-assessed health-related quality of life . MEASUREMENTS Participants completed a structured interview on demographics and medical history and an HUI question naire ( version 3 ) . Routine laboratory test results captured into the study data base , and serum testosterone measured within 3 months after initiation of the baseline hemodialysis session . RESULTS During a median follow-up of 20 ( range , 1 - 81 ) months , 166 ( 27 % ) died and 98 ( 20 % ) had a CV event . Mean serum testosterone level was 234.1 ± 146.1 ( SD ) ng/dL. Higher serum testosterone levels were associated with significantly decreased unadjusted risk of death ( HR per 10-ng/dL increase , 0.58 ; 95 % CI , 0.37 - 0.90 ) . There was a statistically significant trend for higher all-cause mortality with low serum testosterone levels in adjusted analyses ( P < 0.001 ) . Higher levels of log-transformed testosterone were associated with significantly higher HUI scores ( P for trend < 0.001 ) , and low levels of serum testosterone were associated significantly with lower HUI scores ( P for trend < 0.001 ) . Although there was a significant trend in the unadjusted risk of CV events among participants with low serum testosterone levels ( P < 0.001 ) , the risk was no longer significant after adjustment for age . There was no significant interaction with age and serum testosterone level tested as continuous variables ( P = 0.07 ) . LIMITATIONS A short follow-up period and serum testosterone measured on a single occasion . CONCLUSIONS Low serum testosterone concentration may be a modifiable risk factor for adverse outcomes and poor quality of life in male hemodialysis patients . This hypothesis should be tested in r and omized controlled trials Objective To evaluate the cardiovascular ( CV ) complications associated with  orchiectomy ( OE )  and parenteral polyestradiol phosphate ( PEP ) therapy ( 240 mg/month ) , taking into account the effect of pretreatment diseases and pretreatment medication . Material and methods A total of 244 T3–4 M0 patients and 200 T1–4 M1 patients were r and omized to either OE or PEP therapy .  The two groups of patients were analyzed separately . The follow-up period was 36 months . The effect of pretreatment vascular and other diseases and pretreatment medication which may be associated with a risk of CV complications was evaluated . Results In the T3–4 M0 patients , the treatment ( PEP versus OE ) and the presence of pretreatment vascular diseases were statistically significantly associated with a risk of CV complications ( p=0.01 and 0.003 , respectively ) . In the T1–4 M1 patients , such an association was not found . No association was observed between pretreatment medication and CV complications . There was no difference in progression-free time between the therapy groups in either the T3–4 M0 or T1–4 M1 patients . Conclusion In patients with locally advanced prostatic cancer  , PEP therapy is associated with a statistically significantly higher risk of CV complications compared to OE ABSTRACT Objective : To assess the effect of raloxifene 60 mg/day ( RLX ) on year-by-year cardiovascular ( CV ) events in postmenopausal women participating in the Multiple Outcomes of Raloxifene Evaluation ( MORE ) trial , a double-blind , placebo-controlled osteoporosis treatment trial . Research design and methods : Post hoc analysis , using data from participants receiving placebo ( N = 2576 ) or RLX 60 mg/day ( N = 2557 ) in MORE , was performed to determine the relative risk ( RR , 95 % CI ) of CV events in each individual trial year . Analyses were performed for the overall cohort and for women in high and low risk subsets . Women were retrospectively assessed as high CV risk using established criteria and the remaining women were considered low CV risk . Results : The incidence of CV events did not differ between the RLX and placebo groups in the overall cohort ( RR 0.86 , 95 % CI 0.64–1.15 ) , or the low CV risk subset ( RR 1.01 , 95 % CI 0.70–1.46 ) . In the high-risk subset , the incidence of CV events was less in the RLX group ( RR 0.60 , 95 % CI 0.38–0.95 ) . There was no significant increase in CV risk during any single year in the RLX group for either the overall cohort or the low or high CV risk subsets . Conclusion : In this post hoc analysis , the risk of CV events was not increased in any single year of MORE in women taking RLX , either in the overall cohort or in the low and high CV risk subsets Background . Cardiovascular disease remains epidemic in transplant recipients , despite aggressive treatment of cardiovascular risk factors . Thus , novel risk factors could play a role in the genesis of cardiovascular events in this population . Methods . We evaluated the impact of early posttransplant anemia on cardiovascular events . We examined rolling average hematocrit values at 30-day intervals and determined the effect of increasing hematocrit on the risk for cardiovascular ( CV ) events in a single-center population of 404 type 1 diabetic end-stage renal disease patients who underwent either cadaveric kidney transplantation alone or simultaneous pancreas-kidney transplantation .  Results . Greater than 60 % of the individuals in the study cohort had hematocrit less than or equal to 30 % at least once during the first 30 days posttransplant . Forty-two individuals ( 10.4 % of the study population ) had at least one 30-day rolling hematocrit less than or equal to 30 % and a CV event ( myocardial infa rct ion , CV death , angina , congestive heart failure ) during the first 26 weeks of the posttransplant course . Increasing hematocrit ( > 30 % ) led to a reduction in the risk ratio ( RR ) for a CV event compared with hematocrit less than or equal to 30 % ( RR , 0.237 ; P = 0.015 ) . The association between anemia and CV events remained statistically significant in a multivariate analysis ( RR , 0.65 ; P = 0.022 ) that also included age and a history of pretransplant ischemic heart disease . Conclusions . These data suggest that anemia is an important risk factor for early posttransplant CV events in a high-risk population . Prospect i ve studies of anemia management therapy in this setting are warranted to determine whether this will reduce early posttransplant CV risk PURPOSE This study examined whether ketoprofen , a nonsteroidal anti-inflammatory drug , attenuated muscle soreness ( SOR ) , improved maximal isometric force ( MIF ) recovery , and /or altered myoelectric activity after high-force eccentric exercise . METHODS 48 subjects were r and omly assigned to one of four groups : CON : no exercise/no drug ( N = 12 ) ; PLA : exercise + placebo ( N = 12 ) ; TRT-100 : exercise + 100 mg oral ketoprofen ( N = 12 ) ; and TRT-25 : exercise + 25 mg oral ketoprofen ( N = 12 ) . PLA , TRT-100 , and TRT-25 were administered in a double-blind fashion . Baseline measurements of SOR , MIF , and surface electromyographic ( EMG ) amplitude were taken , and PLA , TRT-100 , and TRT-25 performed 50 maximal eccentric contractions of the elbow flexors ; 36 h later , subjects reporting moderate soreness were given ketoprofen or placebo and SOR measures were taken hourly for 8 h. EMG amplitude was assessed during MIF before dosing and again 8 h later and during submaximal contractions of 5 % , 10 % , and 20 % of MIF before dosing and hourly for 8 h. RESULTS Eccentric exercise increased myoelectric activity during submaximal force measurements in PLA , TRT-100 , and TRT-25 in all conditions . Ketoprofen had no effect on reducing this increase in EMG activity . Ketoprofen attenuated perceived SOR ( P < 0.05 ) and enhanced MIF recovery ( P < 0.05 ) compared with placebo . TRT-100 and TRT-25 demonstrated 10 % and 19 % reductions in SOR , respectively , and 16 % and 9 % increases in MIF , respectively , whereas PLA demonstrated a 1 % increase in SOR and 9 % decrease in MIF over 8 h. CONCLUSION Ketoprofen treatment after muscle damaging exercise reduces muscle soreness and improves force recovery OBJECTIVE To assess the efficacy and safety of testosterone replacement in males with late-onset hypogonadism compared to hypogonadal men without replacement , and controls , during six months . METHODS We assessed , through ADAM , AMS , IIEF-5 and SF-36 question naires , and through clinical and laboratory examinations , 62 patients divided into three groups : 17 hypogonadal males ( HR ) used intramuscular testosterone every three weeks ; 14 hypogonadal males ( HV ) and 31 non-hypogonadal males ( CV ) used  oral vitamins daily . RESULTS When compared to others , HR group obtained libido improvement assessed by ADAM 1 ( p = 0.004 ) , and borderline sexual potency improvement assessed by IIEF-5 ( p = 0.053 ) , besides a decrease in waist circumference after eight weeks ( p = 0.018 ) . The remaining parameters did not differ between the groups . PSA and hematocrit remained stable in those using testosterone . CONCLUSION Six months of testosterone replacement improved sexuality and body composition , with prostatic and hematological safety Background Physical therapy is recommended for the management of axial spondyloarthritis ( axSpA ) and flexibility exercises have traditionally been the main focus . Cardiovascular ( CV ) diseases are considered as a major health concern in axSpA and there is strong evidence that endurance and strength exercise protects against CV diseases . Therefore , the aim of this study was to investigate the efficacy of high intensity endurance and strength exercise on disease activity and CV health in patients with active axSpA. Methods In a single blinded r and omized controlled pilot study the exercise group ( EG ) performed 12 weeks of endurance and strength exercise while the control group ( CG ) received treatment as usual . The primary outcome was the Ankylosing Spondylitis ( AS ) Disease Activity Score ( ASDAS ) . Secondary outcomes included patient reported disease activity ( Bath AS Disease Activity Index [ BASDAI ] ) , physical function ( Bath AS Functional Index [ BASFI ] ) , and CV risk factors measured by arterial stiffness ( Augmentation Index [ Alx ] ) and Pulse Wave Velocity [ PWV ] ) , cardiorespiratory fitness ( VO2 peak ) and body composition . ANCOVA on the post intervention values with baseline values as covariates was used to assess group differences , and Mann Whitney U-test was used for outcomes with skewed residuals . Results Twenty-eight patients were included and 24 ( EG , n = 10 , CG , n = 14 ) completed the study . A mean treatment effect of −0.7 ( 95%CI : −1.4 , 0.1 ) was seen in ASDAS score . Treatment effects were also observed in secondary outcomes ( mean group difference [ 95%CI ] ) : BASDAI : −2.0 ( −3.6 , −0.4 ) , BASFI : −1.4 ( −2.6 , −0.3 ) , arterial stiffness ( estimated median group differences [ 95 % CI ] ) : AIx ( % ) : −5.3 ( −11.0 , −0.5 ) , and for PVW ( m/s ) : −0.3 ( −0.7 , 0.0 ) , VO2 peak ( ml/kg/min ) ( mean group difference [ 95%CI ] : 3.7 ( 2.1 , 5.2 ) and trunk fat ( % ) : −1.8 ( −3.0 , −0.6 ) . No adverse events occurred . Conclusion High intensity exercise  improved disease activity and reduced CV risk factors in patients with active axSpA. These effects will be further explored in a larger trial . Trial Registration Clinical Trials.gov BACKGROUND AND AIMS Abdominal obesity ( AO ) is associated with endothelial function ( EF ) alteration and increased global cardiovascular ( CV ) risk .  Therapeutic lifestyle changes ( TLSC ) reduce CV risk , but the impact on EF assessed by peripheral artery tonometry ( PAT ) is unknown . In this study , we aim ed to prospect ively assess the effects of TLSC on EF measured by PAT in increased CV risk patients with AO . METHODS AND RESULTS 150 patients with AO and moderate CV risk were r and omized to groups receiving a one-year intervention of either conventional medical care ( control group , CG ) or an intensive TLSC program ( intervention group , IG ) . Vascular studies ( EF by PAT , intima-media thickness ( IMT ) ) and lifestyle ( LS ) assessment were performed before and after intervention . The PAT ratio improved in the IG and worsened in the CG . The global CV risk was reduced ( P = 0.017 ) in the IG due to a significant decrease in systolic blood pressure ( P < 0.001 ) , increase in HDL cholesterol and ApolipoproteinA1 ( P = 0.013 ) . More individuals in the IG than in the CG quit smoking ( P = 0.001 ) and increased their physical activity ( P = 0.014 ) . The improvement in at least two LS components was associated with a PAT ratio increase ( 2.44 IC : 95 % 0.99 - 6.00 , P = 0.051 ) . The PAT ratio increase determined less IMT progression ( -1.1 IC : 95 % 0.91 - 1.00 , P = 0.053 ) . CONCLUSIONS Good adherence to a TLSC program reduces global CV risk and determines PAT ratio improvement . The PAT ratio increase is the main determinant of lower IMT progression BACKGROUND Renal impairment is strongly linked to adverse cardiovascular ( CV ) events . Baseline renal dysfunction is a strong predictor of CV mortality and morbidity in patients admitted with acute coronary syndrome ( ACS ) . However , the prognostic importance of worsening renal function ( WRF ) in these patients is not well characterized . METHODS ACS patients enrolled in the SPACE ( Saudi Project for Assessment of Coronary Events ) registry who had baseline and pre-discharge serum creatinine data available were eligible for this study . WRF was defined as a 25 % reduction from admission estimated glomerular filtration rate ( eGFR ) within 7 days of hospitalization . Baseline demographics , clinical presentation , therapies , and in-hospital outcomes were compared . RESULTS Of the 3583 ACS patients , WRF occurred in 225 patients ( 6.3 % ) , who were older , had more cardiovascular risk factors , were more likely to be female , have past vascular disease , and presented with more non-ST-segment elevation myocardial infa rct ion than patients without WRF ( 39.5 % vs. 32.8 % ; p=0.042 ) . WRF was associated with an increased risk of in-hospital death , heart failure , cardiogenic shock , and stroke . After adjusting for potential confounders , WRF was an independent predictor of in-hospital death ( adjusted odd ratio 28.02 , 95 % CI 13.2 - 60.28 , p<0.0001 ) . WRF was more predictive of mortality than baseline eGFR . CONCLUSION These results indicate that WRF is a powerful predictor for in-hospital mortality and CV complications in ACS patients Background and Purpose — Previous studies have shown that repeated sensory inputs could enhance brain plasticity and cortical motor output . The purpose of this study was to investigate whether combining electrically induced sensory inputs through transcutaneous electrical nerve stimulation ( TENS ) with task-related training ( TRT ) in a home-based program would augment voluntary motor output in chronic stroke survivors better than either treatment alone or no treatment . Methods — Eighty-eight patients with stroke were assigned r and omly to receive a home-based program of ( 1 ) TENS , ( 2 ) TENS+TRT , ( 3 ) placebo TENS+TRT , or ( 4 ) no treatment ( control ) 5 days a week for 4 weeks . Outcome measurements included Composite Spasticity Scale , peak torques generated during maximum isometric voluntary contraction of ankle dorsiflexors and plantarflexors , and gait velocity recorded at baseline , after 2 and 4 weeks of treatment , and 4 weeks after treatment ended . Results — When compared with TENS , the combined TENS+TRT group showed significantly greater improvement in ankle dorsiflexion torque at follow-up and in ankle plantarflexion torque at week 2 and follow-up ( P<0.01 ) . When compared with placebo+TRT , the TENS+TRT group produced earlier and greater reduction of plantarflexor spasticity and improvement in ankle dorsiflexion torque at week 2 ( P<0.01 ) . When compared with all 3 groups , the TENS+TRT group showed significantly greater improvement in gait velocity ( P<0.01 ) . Conclusions — In patients with chronic stroke , 20 sessions of a combined TENS+TRT home-based program decreased plantarflexor spasticity , improved dorsiflexor and plantarflexor strength , and increased gait velocity significantly more than TENS alone , placebo+TRT , or no treatment . Such improvements can even be maintained 4 weeks after treatment ended Background Cardiovascular ( CV ) disease has a major impact on patients with rheumatoid arthritis ( RA ) , however , the relative contributions of traditional CV risk factors and markers of RA severity are unclear . The authors examined the relative importance of traditional CV risk factors and RA markers in predicting CV events . Methods A prospect i ve longitudinal cohort study was conducted in the setting of the CORRONA registry in the USA . Baseline data from subjects with RA enrolled in the CORRONA registry were examined to determine predictors of CV outcomes , including myocardial infa rct ion , stroke or transient ischemic attack . Possible predictors were of two types : traditional CV risk factors and markers of RA severity . The discriminatory value of these variables was assessed by calculating the area under the receiver operating characteristic curve ( c-statistic ) in logistic regression . The authors then assessed the incidence rate for CV events among subjects with an increasing number of traditional CV risk factors and /or RA severity markers . Results The cohort consisted of 10 156 patients with RA followed for a median of 22 months . The authors observed 76 primary CV events during follow-up for a composite event rate of 3.98 ( 95 % CI 3.08 to 4.88 ) per 1000 patient-years . The c-statistic improved from 0.57 for models with only CV risk factors to 0.67 for models with CV risk factors plus age and gender . The c-statistic improved further to 0.71 when markers of RA severity were also added . The incidence rate for CV events was 0 ( 95 % CI 0 to 5.98 ) for persons without any CV risk factors or markers of RA severity , while in the group with two or more CV risk factors and three or more markers of RA severity the incidence was 7.47 ( 95 % CI 4.21 to 10.73 ) per 1000 person-years . Conclusions Traditional CV risk factors and markers of RA severity both contribute to models predicting CV events . Increasing numbers of both types of factors are associated with greater risk The higher mortality rate among rheumatoid arthritis ( RA ) patients in comparison with the general population is largely attributable to cardiovascular ( CV ) disease , particularly coronary atherosclerosis , but also non-fatal myocardial infa rct ion and heart failure . It may be due to RA-specific risk factors such as hyperhomocysteinemia , disease-related dyslipidemia or vascular inflammation , or morbidity related to high levels of cytokines such as tumour necrosis factor ( TNF ) and RA medications . Non-steroidal anti-inflammatory drugs ( NSAIDs ) are among the most important in rheumatology , but many are associated with CV disease . A number of r and omised control trials have shown that , although exposure to low doses of corticosteroids for 1 - 3years does not significantly increase CV risk , longer exposure can increase CV events . The use of disease-modifying antirheumatic drugs ( DMARDs ) , particularly methotrexate , increases homocysteinemia , reduces inflammation and improves lipid profiles , thus reducing the development of atherosclerosis and clinical ly overt CVD . Although contraindicated in RA patients with severe heart failure , biological agents such as anti-TNF agents delay and even reverse the progression of endothelial dysfunction and atherosclerosis .  Tocilizumab leads to changes in lipid profiles without increasing adverse vascular events . The effects on the CV system depend on the drug itself , the dose and the period of exposure , and so CV risk should be evaluated before starting treatment with any drug OBJECTIVE To evaluate the effectiveness of 2 rehabilitative approaches for improving paretic limb reaching by chronic stroke subjects . DESIGN Pre- and posttest reaching to targets ipsilateral , midline , and contralateral to the impaired side . SETTING Training in subjects ' homes ; testing in a laboratory setting . PARTICIPANTS Twelve poststroke volunteers were matched using the Motor Assessment Scale ( MAS ) and then were r and omly assigned to 1 of 2 training conditions . Subjects were subsequently categorized as at a high or low functional level , using the reaching pretest movement time scores . INTERVENTIONS Training ( trunk unrestrained ) using the paretic limb was 4 weeks ( 12 sessions ) . Task-related training ( TRT ) involved reaching to objects placed across the workspace . Progressive resistive exercise ( PRE ) involved whole-arm pulling against resistive therapeutic tubing in planes and distances similar to that in TRT . Main outcome measures Kinematic analysis of arm trajectory and trunk motion using the Peak Performance System , as well as scores on the MAS and the Rivermead Motor Assessment ( RMA ) . RESULTS For low-level groups , TRT result ed in increased substitutive trunk use at the target ipsilateral to the moving arm , and for midline and contralateral targets after PRE . Only low-level , TRT subjects straightened h and paths , which suggested better coordination of elbow-shoulder motion , and improved on the RMA . High-level subjects decreased trunk use at ipsilateral target after PRE , which was not observed after TRT . No significant differences between training conditions were found for other kinematic variables . CONCLUSIONS Training benefits appear to depend on initial level of functioning . Although compensatory trunk use was evident , low-level subjects seemed to benefit most from TRT . High-level subjects , whose kinematics showed fairly normal movement organization , demonstrated less compensatory movement after PRE BACKGROUND Asymptomatic hyperuricemia increases renal and cardiovascular ( CV ) risk  . We previously conducted a 2-year , single-blind , r and omized , controlled trial of allopurinol treatment that showed improved estimated glomerular filtration rate and reduced CV risk . STUDY DESIGN Post hoc analysis of a long-term follow-up after completion of the 2-year trial . SETTING & PARTICIPANTS 113 participants ( 57 in the allopurinol group and 56 in the control group ) initially followed up for 2 years and 107 participants followed up to 5 additional years . INTERVENTION Continuation of allopurinol treatment , 100mg/d , or st and ard treatment .  OUTCOME Renal event ( defined as starting dialysis therapy and /or doubling serum creatinine and /or ≥50 % decrease in estimated estimated glomerular filtration rate ) and CV events ( defined as myocardial infa rct ion , coronary revascularization or angina pectoris , congestive heart failure , cerebrovascular disease , and peripheral vascular disease ) . RESULTS During initial follow-up , there were 2 renal and 7 CV events in the allopurinol group compared with 6 renal and 15 CV events in the control group . In the long-term follow-up period , 12 of 56 participants taking allopurinol stopped treatment and 10 of 51 control participants received allopurinol . During long-term follow-up , an additional 7 and 9 participants in the allopurinol group experienced a renal or CV event , respectively , and an additional 18 and 8 participants in the control group experienced a renal or CV event , respectively . Thus , during the initial and long-term follow-up ( median , 84 months ) , 9 patients in the allopurinol group had a renal event compared with 24 patients in the control group ( HR , 0.32 ; 95 % CI , 0.15 - 0.69 ; P=0.004 ; adjusted for age , sex , baseline kidney function , uric acid level , and renin-angiotensin-aldosterone system blockers ) . Overall , 16 patients treated with allopurinol experienced CV events compared with 23 in the control group ( HR , 0.43 ; 95 % CI , 0.21 - 0.88 ; P=0.02 ; adjusted for age , sex , and baseline kidney function ) . LIMITATIONS Small sample size , single center , not double blind , post hoc follow-up and analysis . CONCLUSIONS Long-term treatment with allopurinol may slow the rate of progression of kidney disease and reduce CV risk BACKGROUND The combination of chemotherapy with thoracic radiotherapy ( TRT ) compared with TRT alone has been shown to confer a survival advantage for good performance status patients with stage III non-small cell lung cancer . However , it is not known whether sequential or concurrent delivery of these therapies is the optimal combination strategy . METHODS A total of 610 patients were r and omly assigned to two concurrent regimens and one sequential chemotherapy and TRT regimen in a three-arm phase III trial . The sequential arm included cisplatin at 100 mg/m2 on days 1 and 29 and vinblastine at 5 mg/m2 per week for 5 weeks with 63 Gy TRT delivered as once-daily fractions beginning on day 50 . Arm 2 used the same chemotherapy regimen as arm 1 with 63 Gy TRT delivered as once-daily fractions beginning on day 1 [ corrected ] . Arm 3 used cisplatin at 50 mg/m2 on days 1 , 8 , 29 , and 36 with oral etoposide at 50 mg twice daily for 10 weeks on days 1 , 2 , 5 , and 6 with 69.6 Gy delivered as 1.2 Gy twice-daily fractions beginning on day 1 . The primary endpoint was overall survival , and secondary endpoints included tumor response and time to tumor progression . Kaplan-Meier analyses were used to assess survival , and toxic effects were examined using the Wilcoxon rank sum test . All statistical tests were two-sided . RESULTS Median survival times were 14.6 , 17.0 , and 15.6 months for arms 1 - 3 , respectively . Five-year survival was statistically significantly higher for patients treated with the concurrent regimen with once-daily TRT compared with the sequential treatment ( 5-year survival : sequential , arm 1 , 10 % [ 20 patients ] , 95 % confidence interval [ CI ] = 7 % to 15 % ; concurrent , arm 2 , 16 % [ 31 patients ] , 95 % CI = 11 % to 22 % , P = .046 ; concurrent , arm 3 , 13 % [ 22 patients ] , 95 % CI = 9 % to 18 % ) . With a median follow-up time of 11 years , the rates of acute grade 3 - 5 nonhematologic toxic effects were higher with concurrent than sequential therapy , but late toxic effects were similar . CONCLUSION Concurrent delivery of cisplatin-based chemotherapy with TRT confers a long-term survival benefit compared with the sequential delivery of these therapies
Conclusions Oral TRT produces significant CV risk .
Differences in the degree to which serum DHT is elevated may underlie the varying CV risk by TRT administration route , as elevated serum dihydrotestosterone has been shown to be associated with CV risk in observational studies
Background Potential cardiovascular ( CV ) risks of testosterone replacement therapy ( TRT ) are currently a topic of intense interest .
However , no studies have addressed CV risk as a function of the route of administration of TRT .