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.
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
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 .