Hormonal predictors of prostate cancer: a meta-analysis.

PURPOSE: Although there is strong circumstantial evidence that androgens are implicated in the etiology of prostate cancer, epidemiologic investigations have failed to demonstrate consistently that one or more steroid hormones are implicated. In contrast, recent epidemiologic studies unequivocally link serum insulin-like growth factor 1 (IGF-1) levels with risk for prostate cancer. METHODS: We have performed the first meta-analysis of all previously published studies on hormonal predictors of risk for prostate cancer. RESULTS: A meta-analysis restricted to studies that performed mutual adjustment for all measured serum hormones, age, and body mass index indicated that men whose total testosterone is in the highest quartile are 2.34 times more likely to develop prostate cancer (95% confidence interval, 1.30 to 4.20). In contrast, levels of dihydrotestosterone and estradiol do not seem to play a role of equal importance. The only study that provides multivariably adjusted sex hormone-binding globulin data indicates that this binding protein is inversely related to prostate cancer risk (odds ratio, 0.46; 95% confidence interval, 0.24 to 0.89). Finally, all three studies that examined the role of serum IGF-1 have consistently demonstrated a positive and significant association with prostate cancer risk that is similar in magnitude to that of testosterone. CONCLUSION: Men with either serum testosterone or IGF-1 levels in upper quartile of the population distribution have an approximately two-fold higher risk for developing prostate cancer.

Faculty training in general internal medicine: a survey of graduates from a research-intensive fellowship program.

PURPOSE: To determine the fellowship experiences and career activities of the graduates of a research-intensive general internal medicine fellowship program. METHOD: In 1997, the authors surveyed all graduates of the Harvard General Internal Medicine Fellowship Program, a research-intensive fellowship begun in 1979. RESULTS: Of 105 surveys delivered to graduates, 103 (98%) were returned. During the fellowship, 82 graduates (80%) presented research findings at regional or national meetings, 89 (86%) published peer-reviewed articles based on their fellowship work, 75 (73%) precepted residents or medical students in the ambulatory setting, and 67 (65%) taught medical students in the preclinical years. At the time of the survey, 100 graduates (97%) held academic appointments: 48 as clinician-investigators, 23 as clinician-administrators, 15 as clinician-educators, and 15 as clinicians. CONCLUSION: Graduates of this research-intensive fellowship pursued academic careers with research, teaching, administration, and clinical activities. Directors of similar fellowship programs should prepare their graduates for all these activities.

Are guidelines following guidelines? The methodological quality of clinical practice guidelines in the peer-reviewed medical literature.

CONTEXT: Practice guidelines play an important role in medicine. Methodological principles have been formulated to guide their development. OBJECTIVE: To determine whether practice guidelines in peer-reviewed medical literature adhered to established methodological standards for practice guidelines. DESIGN: Structured review of guidelines published from 1985 through June 1997 identified by a MEDLINE search. MAIN OUTCOME MEASURES: Mean number of standards met based on a 25-item instrument and frequency of adherence. RESULTS: We evaluated 279 guidelines, published from 1985 through June 1997, produced by 69 different developers. Mean overall adherence to standards by each guideline was 43.1% (10.77/25). Mean (SD) adherence to methodological standards on guideline development and format was 51.1% (25.3%); on identification and summary of evidence, 33.6% (29.9%); and on the formulation of recommendations, 46% (45%). Mean adherence to standards by each guideline improved from 36.9% (9.2/25) in 1985 to 50.4% (12.6/25) in 1997 (P<.001). However, there was little improvement over time in adherence to standards on identification and summary of evidence from 34.6% prior to 1990 to 36.1 % after 1995 (P = .11). There was no difference in the mean number of standards satisfied by guidelines produced by subspecialty medical societies, general medical societies, or government agencies (P = .55). Guideline length was positively correlated with adherence to methodological standards (P = .001). CONCLUSION: Guidelines published in the peer-reviewed medical literature during the past decade do not adhere well to established methodological standards. While all areas of guideline development need improvement, greatest improvement is needed in the identification, evaluation, and synthesis of the scientific evidence.

The efficacy of ticarcillin-clavulanate and gentamicin as empiric treatment for febrile neutropenic pediatric patients with cancer.

The therapeutic efficacy of ticarcillin-clavulanate and gentamicin was assessed in 56 pediatric cancer patients with 95 febrile neutropenic episodes. The mean temperature of these children on admission was 102 degrees F (range 101 degrees to 106 degrees F), with a median absolute neutrophil count of 60. The median hospital stay was 7 days. All of the patients had one of two types of permanent central lines (Port-A-Cath, N = 75; Hickman, N = 20). Of 20 episodes of bacteremia, 17 had microbial isolates that were gram-positive bacteria and 8 of these episodes required the addition of vancomycin. Clinical cure was achieved in 84 of the 95 febrile episodes (88%) with the use of ticarcillin-clavulanate and gentamicin. There were no fatalities, nor were there any major toxicities. We conclude that the combination of ticarcillin-clavulanate and gentamicin is an effective initial empirical therapy for febrile neutropenic children with cancer. Gram-positive pathogens are the usual cause of breakthrough bacteremia in this clinical setting of central line usage, and associated morbidity and mortality from these organisms are low.