Mohamed B. Elamin

Adverse Effects of Testosterone Therapy in Adult Men: A Systematic Review and Meta-Analysis

CONTEXT The risks of testosterone therapy in men remain poorly understood. OBJECTIVE The aim of this study was to conduct a systematic review and meta-analyses of testosterone trials to evaluate the adverse effects of testosterone treatment in men. DATA SOURCES We searched MEDLINE, EMBASE, and Cochrane CENTRAL from 2003 through August 2008. Review of reference lists and contact with experts further identified candidate studies. STUDY SELECTION Eligible studies were comparative, randomized, and nonrandomized and reported the effects of testosterone on outcomes of interest (death, cardiovascular events and risk factors, prostate outcomes, and erythrocytosis). Reviewers, working independently and in duplicate, determined study eligibility. DATA EXTRACTION Reviewers working independently and in duplicate determined the methodological quality of studies and collected descriptive, quality, and outcome data. DATA SYNTHESIS The methodological quality of the 51 included studies varied from low to medium, and follow-up duration ranged from 3 months to 3 yr. Testosterone treatment was associated with a significant increase in hemoglobin [weighted mean difference (WMD), 0.80 g/dl; 95% confidence interval (CI), 0.45 to 1.14] and hematocrit (WMD, 3.18%; 95% CI, 1.35 to 5.01), and a decrease in high-density lipoprotein cholesterol (WMD, -0.49 mg/dl; 95% CI, -0.85 to -0.13). There was no significant effect on mortality, prostate, or cardiovascular outcomes. CONCLUSIONS The adverse effects of testosterone therapy include an increase in hemoglobin and hematocrit and a small decrease in high-density lipoprotein cholesterol. These findings are of unknown clinical significance. Current evidence about the safety of testosterone treatment in men in terms of patient-important outcomes is of low quality and is hampered by the brief study follow-up.

Sexual Abuse and Lifetime Diagnosis of Psychiatric Disorders: Systematic Review and Meta-analysis

OBJECTIVE To systematically assess the evidence for an association between sexual abuse and a lifetime diagnosis of psychiatric disorders. PATIENTS AND METHODS We performed a comprehensive search (from January 1980-December 2008, all age groups, any language, any population) of 9 databases: MEDLINE, EMBASE, CINAHL, Current Contents, PsycINFO, ACP Journal Club, CCTR, CDSR, and DARE. Controlled vocabulary supplemented with keywords was used to define the concept areas of sexual abuse and psychiatric disorders and was limited to epidemiological studies. Six independent reviewers extracted descriptive, quality, and outcome data from eligible longitudinal studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled across studies by using the random-effects model. The I(2) statistic was used to assess heterogeneity. RESULTS The search yielded 37 eligible studies, 17 case-control and 20 cohort, with 3,162,318 participants. There was a statistically significant association between sexual abuse and a lifetime diagnosis of anxiety disorder (OR, 3.09; 95% CI, 2.43-3.94), depression (OR, 2.66; 95% CI, 2.14-3.30), eating disorders (OR, 2.72; 95% CI, 2.04-3.63), posttraumatic stress disorder (OR, 2.34; 95% CI, 1.59-3.43), sleep disorders (OR, 16.17; 95% CI, 2.06-126.76), and suicide attempts (OR, 4.14; 95% CI, 2.98-5.76). Associations persisted regardless of the victims sex or the age at which abuse occurred. There was no statistically significant association between sexual abuse and a diagnosis of schizophrenia or somatoform disorders. No longitudinal studies that assessed bipolar disorder or obsessive-compulsive disorder were found. Associations between sexual abuse and depression, eating disorders, and posttraumatic stress disorder were strengthened by a history of rape. CONCLUSION A history of sexual abuse is associated with an increased risk of a lifetime diagnosis of multiple psychiatric disorders.

Vitamin D and Cardiovascular Outcomes: A Systematic Review and Meta-Analysis

CONTEXT Several studies found association between vitamin D levels and hypertension, coronary artery calcification, and heart disease. OBJECTIVE The aim of this study was to summarize the evidence on the effect of vitamin D on cardiovascular outcomes. DESIGN AND METHODS We searched electronic databases from inception through August 2010 for randomized trials. Reviewers working in duplicate and independently extracted study characteristics, quality, and the outcomes of interest. Random-effects meta-analysis was used to pool the relative risks (RR) and the weighted mean differences across trials. RESULTS We found 51 eligible trials with moderate quality. Vitamin D was associated with nonsignificant effects on the patient-important outcomes of death [RR, 0.96; 95% confidence interval (CI), 0.93, 1.00; P = 0.08], myocardial infarction (RR, 1.02; 95% CI, 0.93, 1.13; P = 0.64), and stroke (RR, 1.05; 95% CI, 0.88, 1.25; P = 0.59). These analyses were associated with minimal heterogeneity. There were no significant changes in the surrogate outcomes of lipid fractions, glucose, or diastolic or systolic blood pressure. The latter analyses were associated with significant heterogeneity, and the pooled estimates were trivial in absolute terms. CONCLUSIONS Trial data available to date are unable to demonstrate a statistically significant reduction in mortality and cardiovascular risk associated with vitamin D. The quality of the available evidence is low to moderate at best.

Sexual Abuse and Lifetime Diagnosis of Somatic Disorders: A Systematic Review and Meta-analysis

CONTEXT Many patients presenting for general medical care have a history of sexual abuse. The literature suggests an association between a history of sexual abuse and somatic sequelae. OBJECTIVE To systematically assess the association between sexual abuse and a lifetime diagnosis of somatic disorders. Data Sources and Extraction A systematic literature search of electronic databases from January 1980 to December 2008. Pairs of reviewers extracted descriptive, quality, and outcome data from included studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled across studies by using the random-effects model. The I(2) statistic was used to assess heterogeneity. STUDY SELECTION Eligible studies were longitudinal (case-control and cohort) and reported somatic outcomes in persons with and without history of sexual abuse. RESULTS The search identified 23 eligible studies describing 4640 subjects. There was a significant association between a history of sexual abuse and lifetime diagnosis of functional gastrointestinal disorders (OR, 2.43; 95% CI, 1.36-4.31; I(2) = 82%; 5 studies), nonspecific chronic pain (OR, 2.20; 95% CI, 1.54-3.15; 1 study), psychogenic seizures (OR, 2.96; 95% CI, 1.12-4.69, I(2) = 0%; 3 studies), and chronic pelvic pain (OR, 2.73; 95% CI, 1.73-4.30, I(2) = 40%; 10 studies). There was no statistically significant association between sexual abuse and a lifetime diagnosis of fibromyalgia (OR, 1.61; 95% CI, 0.85-3.07, I(2) = 0%; 4 studies), obesity (OR, 1.47; 95% CI, 0.88-2.46; I(2) = 71%; 2 studies), or headache (OR, 1.49; 95% CI, 0.96-2.31; 1 study). We found no studies that assessed syncope. When analysis was restricted to studies in which sexual abuse was defined as rape, significant associations were observed between rape and a lifetime diagnosis of fibromyalgia (OR, 3.35; 95% CI, 1.51-7.46), chronic pelvic pain (OR, 3.27; 95% CI, 1.02-10.53), and functional gastrointestinal disorders (OR, 4.01; 95% CI, 1.88-8.57). CONCLUSION Evidence suggests a history of sexual abuse is associated with lifetime diagnosis of multiple somatic disorders.

The Effect of Vitamin D on Falls: A Systematic Review and Meta-Analysis

CONTEXT Vitamin D affects bone and muscle health and likely reduces the risk of falls in the elderly. OBJECTIVE The aim of this systematic review is to summarize the existing evidence on vitamin D use and the risk of falls. DATA SOURCES We searched electronic databases from inception through August 2010. STUDY SELECTION Eligible studies were randomized controlled trials in which the intervention was vitamin D and the incidence of falls was reported. DATA EXTRACTION Reviewers working in duplicate and independently extracted study characteristics, quality, and outcomes data. DATA SYNTHESIS Odds ratio and associated 95% confidence interval were estimated from each study and pooled using the random effects model. RESULTS We found 26 eligible trials of moderate quality that enrolled 45,782 participants, the majority of which were elderly and female. Vitamin D use was associated with statistically significant reduction in the risk of falls (odds ratio for suffering at least one fall, 0.86; 95% confidence interval, 0.77-0.96). This effect was more prominent in patients who were vitamin D deficient at baseline and in studies in which calcium was coadministered with vitamin D. The quality of evidence was low to moderate because of heterogeneity and publication bias. CONCLUSIONS Vitamin D combined with calcium reduces the risk of falls. The reduction in studies without calcium coadministration did not reach statistical significance. The majority of the evidence is derived from trials enrolling elderly women.

Hormonal therapy and sex reassignment: a systematic review and meta‐analysis of quality of life and psychosocial outcomes

Objective  To assess the prognosis of individuals with gender identity disorder (GID) receiving hormonal therapy as a part of sex reassignment in terms of quality of life and other self‐reported psychosocial outcomes.

The effect of vitamin D on falls

CONTEXT Vitamin D affects bone and muscle health and likely reduces the risk of falls in the elderly. OBJECTIVE The aim of this systematic review is to summarize the existing evidence on vitamin D use and the risk of falls. DATA SOURCES We searched electronic databases from inception through August 2010. STUDY SELECTION Eligible studies were randomized controlled trials in which the intervention was vitamin D and the incidence of falls was reported. DATA EXTRACTION Reviewers working in duplicate and independently extracted study characteristics, quality, and outcomes data. DATA SYNTHESIS Odds ratio and associated 95% confidence interval were estimated from each study and pooled using the random effects model. RESULTS We found 26 eligible trials of moderate quality that enrolled 45,782 participants, the majority of which were elderly and female. Vitamin D use was associated with statistically significant reduction in the risk of falls (odds ratio for suffering at least one fall, 0.86; 95% confidence interval, 0.77-0.96). This effect was more prominent in patients who were vitamin D deficient at baseline and in studies in which calcium was coadministered with vitamin D. The quality of evidence was low to moderate because of heterogeneity and publication bias. CONCLUSIONS Vitamin D combined with calcium reduces the risk of falls. The reduction in studies without calcium coadministration did not reach statistical significance. The majority of the evidence is derived from trials enrolling elderly women.

Hypoglycemia with Intensive Insulin Therapy: A Systematic Review and Meta-Analyses of Randomized Trials of Continuous Subcutaneous Insulin Infusion Versus Multiple Daily Injections

CONTEXT Hypoglycemia limits the efficacy of intensive insulin therapy. The extent to which continuous insulin infusion (CSII) overcomes this limitation is unclear. OBJECTIVE The aim was to summarize evidence on the effect of CSII and multiple daily injections (MDIs) on glycemic control and hypoglycemia. DATA SOURCES We searched electronic databases between 2002 and March 2008. STUDY SELECTION We selected published randomized trials of CSII vs. MDI. DATA EXTRACTION Reviewers working in duplicate and independently extracted study characteristics and quality and differences in glycosylated hemoglobin (HbA1c) and hypoglycemic events. DATA SYNTHESIS We found 15 eligible randomized trials of moderate quality, with elevated baseline and end-of-study HbA1c levels. Patients with type 1 diabetes using CSII had slightly lower HbA1c [random-effects weighted mean difference, -0.2%; 95% confidence interval (CI), -0.3, -0.1, compared with MDI], with no significant difference in severe (pooled odds ratio, 0.48; 95% CI, 0.23, 1.00) or nocturnal hypoglycemia (pooled odds ratio 0.82, 95% CI 0.33, 2.03). Adolescents and adults with type 1 diabetes enrolled in crossover trials had nonsignificantly fewer minor hypoglycemia episodes per patient per week (-0.08; 95% CI, -0.21, 0.06) with CSII than MDI; children enrolled in parallel trials had significantly more episodes (0.68; 95% CI, 0.16, 1.20; P(interaction) = 0.03). Outcomes were not different in patients with type 2 diabetes. CONCLUSIONS Contemporary evidence indicates that compared to MDI, CSII slightly reduced HbA1c in adults with type 1 diabetes, with unclear impact on hypoglycemia. In type 2 diabetes, CSII and MDI had similar outcomes. The effect in patients with hypoglycemia unawareness or recurrent severe hypoglycemia remains unclear because of lack of data.

Accuracy of Diagnostic Tests for Cushing’s Syndrome: A Systematic Review and Metaanalyses

CONTEXT The diagnosis of Cushings syndrome (CS) requires the use of tests of unregulated hypercortisolism that have unclear accuracy. OBJECTIVE Our objective was to summarize evidence on the accuracy of common tests for diagnosing CS. DATA SOURCES We searched electronic databases (MEDLINE, EMBASE, Web of Science, Scopus, and citation search for key articles) from 1975 through September 2007 and sought additional references from experts. STUDY SELECTION Eligible studies reported on the accuracy of urinary free cortisol (UFC), dexamethasone suppression test (DST), and midnight cortisol assays vs. reference standard in patients suspected of CS. DATA EXTRACTION Reviewers working in duplicate and independently extracted study characteristics and quality and data to estimate the likelihood ratio (LR) and the 95% confidence interval (CI) for each result. DATA SYNTHESIS We found 27 eligible studies, with a high prevalence [794 (9.2%) of 8631 patients had CS] and severity of CS. The tests had similar accuracy: UFC (n = 14 studies; LR+ 10.6, CI 5.5-20.5; LR- 0.16, CI 0.08-0.33), salivary midnight cortisol (n = 4; LR+ 8.8, CI 3.5-21.8; LR- 0.07, CI 0-1.2), and the 1-mg overnight DST (n = 14; LR+ 16.4, CI 9.3-28.8; LR- 0.06, CI 0.03-0.14). Combined testing strategies (e.g. a positive result in both UFC and 1-mg overnight DST) had similar diagnostic accuracy (n = 3; LR+ 15.4, CI 0.7-358; LR- 0.11, CI 0.007-1.57). CONCLUSIONS Commonly used tests to diagnose CS appear highly accurate in referral practices with samples enriched with patients with CS. Their performance in usual clinical practice remains unclear.

Patient-Important Outcomes in Registered Diabetes Trials

CONTEXT Concerns about the safety and efficacy of diabetes interventions persist, in part because randomized clinical trials (RCTs) have not measured their effect on patient-important outcomes, ie, death and quality of life (morbidity, pain, function). OBJECTIVE To systematically determine the extent to which ongoing and future RCTs in diabetes will ascertain patient-important outcomes. DATA SOURCES On November 10, 2007, we searched primary RCT registries ClinicalTrials.gov (http://www.clinicaltrials.gov), International Standard Randomized Controlled Trial Number Register (http://isrctn.org), and Australian New Zealand Clinical Trials Registry (http://www.anzctr.org.au). STUDY SELECTION We identified phase 2 through 4 RCTs enrolling patients with diabetes. Of 2019 RCTs, 1054 proved eligible. We randomly sampled 50% of the eligible RCTs (527 of 1054) and selected 436 registered since registration became mandatory (2004). DATA EXTRACTION Pairs of reviewers working independently collected study characteristics and determined the outcomes measured and their type (physiological outcomes, surrogate outcomes thought to reflect an increased risk for patient-important outcomes, and patient-important outcomes). RESULTS Of the 436 registered RCTs included in this analysis, 24 (6%) had not started enrollment, 109 (25%) were actively enrolling, and 303 (69%) had completed enrollment. Primary outcomes were patient-important outcomes in only 78 of 436 RCTs (18%; 95% confidence interval [CI], 14%-22%), physiological and laboratory outcomes in 69 of 436 (16%; 95% CI, 13%-20%), and surrogate outcomes in 268 of 436 (61%; 95% CI, 57%-66%). Patient-important outcomes were reported as primary or secondary outcomes in 201 of 436 (46%; 95% CI, 41%-51%). In multivariate analysis, large trials (odds ratio [OR], 1.10; 95% CI, 1.02-1.19 for every additional 100 patients) and trials of longer duration (OR, 1.03; 95% CI, 1.01-1.06 for every additional 30 days) were more likely while parallel design RCTs (OR, 0.15; 95% CI, 0.05-0.44) and type 2 diabetes trials (OR, 0.23; 95% CI, 0.09-0.61) were less likely to assess patient-important outcomes as a primary outcome. CONCLUSION In this sample of registered ongoing RCTs in diabetes, only 18% included patient-important outcomes as primary outcomes.