Effect of testosterone supplementation with and without a dual 5α-reductase inhibitor on fat-free mass in men with suppressed testosterone production: a randomized controlled trial.

CONTEXT: Steroid 5α-reductase inhibitors are used to treat benign prostatic hyperplasia and androgenic alopecia, but the role of 5α-dihydrotestosterone (DHT) in mediating testosterone's effects on muscle, sexual function, erythropoiesis, and other androgen-dependent processes remains poorly understood. OBJECTIVE: To determine whether testosterone's effects on muscle mass, strength, sexual function, hematocrit level, prostate volume, sebum production, and lipid levels are attenuated when its conversion to DHT is blocked by dutasteride (an inhibitor of 5α-reductase type 1 and 2). DESIGN, SETTING, AND PATIENTS: The 5α-Reductase Trial was a randomized controlled trial of healthy men aged 18 to 50 years comparing placebo plus testosterone enthanate with dutasteride plus testosterone enanthate from May 2005 through June 2010. INTERVENTIONS: Eight treatment groups received 50, 125, 300, or 600 mg/wk of testosterone enanthate for 20 weeks plus placebo (4 groups) or 2.5 mg/d of dutasteride (4 groups). MAIN OUTCOME MEASURES: The primary outcome was change in fat-free mass; secondary outcomes: changes in fat mass, muscle strength, sexual function, prostate volume, sebum production, and hematocrit and lipid levels. RESULTS: A total of 139 men were randomized; 102 completed the 20-week intervention. Men assigned to dutasteride were similar at baseline to those assigned to placebo. The mean fat-free mass gained by the dutasteride groups was 0.6 kg (95% CI, -0.1 to 1.2 kg) when receiving 50 mg/wk of testosterone enanthate, 2.6 kg (95% CI, 0.9 to 4.3 kg) for 125 mg/wk, 5.8 kg (95% CI, 4.8 to 6.9 kg) for 300 mg/wk, and 7.1 kg (95% CI, 6.0 to 8.2 kg) for 600 mg/wk. The mean fat-free mass gained by the placebo groups was 0.8 kg (95% CI, -0.1 to 1.7 kg) when receiving 50 mg/wk of testosterone enanthate, 3.5 kg (95% CI, 2.1 to 4.8 kg) for 125 mg/wk, 5.7 kg (95% CI, 4.8 to 6.5 kg) for 300 mg/wk, and 8.1 kg (95% CI, 6.7 to 9.5 kg) for 600 mg/wk. The dose-adjusted differences between the dutasteride and placebo groups for fat-free mass were not significant (P = .18). Changes in fat mass, muscle strength, sexual function, prostate volume, sebum production, and hematocrit and lipid levels did not differ between groups. CONCLUSION: Changes in fat-free mass in response to graded testosterone doses did not differ in men in whom DHT was suppressed by dutasteride from those treated with placebo, indicating that conversion of testosterone to DHT is not essential for mediating its anabolic effects on muscle. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00493987.

Long-chain omega-3 fatty acids, fish intake, and the risk of type 2 diabetes mellitus.

BACKGROUND: Diet is a key component of a healthy lifestyle in the prevention of type 2 diabetes mellitus (T2DM). The role of long-chain omega-3 (n-3) fatty acids (LCFAs) in the development of T2DM remains unresolved. OBJECTIVE: We examined the association between dietary LCFAs and incidence of T2DM in 3 prospective cohorts of women and men. DESIGN: We followed 195,204 US adults (152,700 women and 42,504 men) without preexisting chronic disease at baseline for 14 to 18 y. Fish and LCFA intakes were assessed at baseline and updated at 4-y intervals by using a validated food-frequency questionnaire. RESULTS: During nearly 3 million person-years of follow-up, 9380 new cases of T2DM were documented. After adjustment for other dietary and lifestyle risk factors, LCFA intake was positively related to incidence of T2DM. The pooled multivariate relative risks in 3 cohorts across increasing quintiles of LCFAs were as follows: 1 (reference), 1.00 (95% CI: 0.91, 1.09), 1.05 (95% CI: 0.97, 1.13), 1.17 (95% CI: 1.07, 1.28), and 1.24 (95% CI: 1.09, 1.40) (P for trend < 0.001). Compared with those who consumed fish less than once per month, the relative risk of T2DM was 1.22 (95% CI: 1.08, 1.39) for women who consumed > or =5 servings fish/wk (P for trend <0.001). CONCLUSIONS: We found no evidence that higher consumption of LCFAs and fish reduces the risk of T2DM. Instead, higher intakes may modestly increase the incidence of this disease. Given the beneficial effects of LCFA intake on many cardiovascular disease risk factors, the clinical relevance of this relation and its possible mechanisms require further investigation.

In hospital outcomes after pancreatectomies: an analysis of a national database from 1996 to 2004.

INTRODUCTION: National complication rates following pancreatectomies have not been systematically reported. METHODS: We queried the national hospital discharge survey (NHDS) database to analyze risk factors associated with mortality and length of stay after pancreatectomies. RESULTS: An estimated 49,346 pancreatectomies were performed from 1996 to 2004. The national mortality rate is 9% with an average length of stay 15 days (Interquartile range 10-23) while the morbidity is 35%. Size of the hospital (<300 beds) (OR 2.76 (95% CI 1.14-6.70, P = 0.02)), post-operative pulmonary edema (OR 2.80 (95% CI 1.28-6.12, P = 0.01)) and sepsis (OR 5.22 (95% CI 1.94-14.11, P = 0.001)) are associated with higher mortality. Patients in larger hospitals (>500 beds) (Rate ratio 0.87 (95% CI 0.83-0.91, P < 0.001)) had a shorter hospital stay. Temporal trends reveal a shorter hospital length of stay in 2004 (Rate ratio 0.86 (95% CI 0.78-0.94, P = 0.001)) as compared to 1996. The percentage of pancreatectomies performed at larger hospitals in 1996 (40%) and 2004 (41%) has remained constant. CONCLUSION: The national mortality and morbidity rates after pancreaticoduodenectomy are 9% and 35%, respectively. Larger hospital size and absence of pulmonary edema and sepsis improves mortality. Larger hospitals have better outcomes although the trend for regionalization is not apparent.

High-end physician migration from India.

OBJECTIVE: To examine the relation between the quality of physicians and migration among alumni of All India Institute of Medical Sciences (AIIMS), New Delhi, India over the period 1989-2000. METHODS: In a retrospective cohort study, data on graduates of AIIMS were collected from entrance exam qualifier lists, the AIIMS alumni directory, convocation records, the American Medical Association and informal alumni networks. The data were analysed by use of 2x2 contingency tables and logistic regression models. FINDINGS: Nearly 54% of AIIMS graduates during 1989-2000 now reside outside India. Students admitted under the general category are twice as likely to reside abroad (95% confidence interval: 1.53-2.99) as students admitted under the affirmative-action category. Recipients of multiple academic awards were 35% more likely to emigrate than non-recipients of awards (95% confidence interval: 1.04-1.76). Multivariate analyses do not change these basic conclusions. CONCLUSION: Graduates from higher quality institutions account for a disproportionately large share of emigrating physicians. Even within high-end institutions, such as AIIMS, better physicians are more likely to emigrate. Interventions should focus on the highly trained individuals in the top institutions that contribute disproportionately to the loss of human resources for health. Our findings suggest that affirmative-action programmes may have an unintended benefit in that they may help retain a subset of such personnel.

Quality of medical training and emigration of physicians from India.

BACKGROUND: Physician 'brain drain' negatively impacts health care delivery. Interventions to address physician emigration have been constrained by lack of research on systematic factors that influence physician migration. We examined the relationship between the quality of medical training and rate of migration to the United States and the United Kingdom among Indian medical graduates (1955-2002). METHODS: We calculated the fraction of medical graduates who emigrated to the United States and the United Kingdom, based on rankings of medical colleges and universities according to three indicators of the quality of medical education (a) student choice, (b) academic publications, and (c) the availability of specialty medical training. RESULTS: Physicians from the top quintile medical colleges and of universities were 2 to 4 times more likely to emigrate to the United States and the United Kingdom than graduates from the bottom quintile colleges and universities. CONCLUSION: Graduates of institutions with better quality medical training have a greater likelihood of emigrating. Interventions designed to counter loss of physicians should focus on graduates from top quality institutions.