Context The efficacy and safety of testosterone replacement therapy (TRT) in hypogonadal men remain incompletely understood. Objective To conduct a systematic review and meta-analysis of randomized clinical trials (RCT) to determine the effects of TRT on patient-important outcomes and adverse events in hypogonadal men. Data Sources We searched Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Database of Systematic Reviews, Ovid Cochrane Central Register of Controlled Trials, and Scopus from inception to March 2th, 2017. Study selection RCTs that assessed the efficacy and adverse events of TRT of at least 12 weeks compared with placebo in adult men with hypogonadism, defined by morning testosterone ≤300 ng/dL and at least one symptom or sign of hypogonadism. Data extraction Reviewers working independently and in duplicate assessed the quality of the trials and collected data on patient characteristics, interventions, and outcomes. Data synthesis We found 11 publications, reporting on 4 eligible trials (including 1,779 patients) at low risk of bias. Compared to placebo, TRT was associated with a small but significant increase in sexual desire or libido [standardized mean difference (SMD): 0.17, 95% CI 0.01, 0.34] (n=1383), erectile function [SMD: 0.16, 95% CI 0.06, 0.27] (n=1344), and sexual satisfaction [SMD: 0.16, 95% CI 0.01, 0.31] (n=676), but had no effect on energy or mood. TRT was associated with an increased risk of developing erythrocytosis [relative risk: 8.14, 95% CI: 1.87, 35.40] (n=1579) compared to placebo, but had no significant effect on lower urinary tract symptoms (LUTS). Conclusion In hypogonadal men TRT improves sexual desire, erectile function, and sexual satisfaction, however it increases the risk of erythrocytosis.

Background Clinicians’ satisfaction with encounter decision aids is an important component in facilitating implementation of these tools. We aimed to determine the impact of decision aids supporting shared decision making (SDM) during the clinical encounter on clinician outcomes. Methods We searched nine databases from inception to June 2017. Randomised clinical trials (RCTs) of decision aids used during clinical encounters with an unaided control group were eligible for inclusion. Due to heterogeneity among included studies, we used a narrative evidence synthesis approach. Results Twenty-five papers met inclusion criteria including 22 RCTs and 3 qualitative or mixed-methods studies nested in an RCT, together representing 23 unique trials. These trials evaluated healthcare decisions for cardiovascular prevention and treatment (n=8), treatment of diabetes mellitus (n=3), treatment of osteoporosis (n=2), treatment of depression (n=2), antibiotics to treat acute respiratory infections (n=3), cancer prevention and treatment (n=4) and prenatal diagnosis (n=1). Clinician outcomes were measured in only a minority of studies. Clinicians’ satisfaction with decision making was assessed in only 8 (and only 2 of them showed statistically significantly greater satisfaction with the decision aid); only three trials asked if clinicians would recommend the decision aid to colleagues and only five asked if clinicians would use decision aids in the future. Outpatient consultations were not prolonged when a decision aid was used in 9 out of 13 trials. The overall strength of the evidence was low, with the major risk of bias related to lack of blinding of participants and/or outcome assessors. Conclusion Decision aids can improve clinicians’ satisfaction with medical decision making and provide helpful information without affecting length of consultation time. Most SDM trials, however, omit outcomes related to clinicians’ perspective on the decision making process or the likelihood of using a decision aid in the future.

Background: Reports have concluded that platelet-rich plasma (PRP) is an effective and safe biological approach in the treatment of knee osteoarthritis (OA). However, no consensus has been established regarding the number of injections required to observe a therapeutic effect. Purpose: To compare the clinical effectiveness reported in randomized controlled trials (RCTs) of single versus multiple PRP injections in the treatment of knee OA. Study Design: Systematic review; Level of evidence, 1. Methods: A comprehensive search was conducted for RCTs published between 1970 and 2019 that compared the effect of single versus multiple PRP injections on pain and functionality in patients with knee OA. Searched databases included MEDLINE, Scopus, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials. A data extraction form was designed to obtain bibliographic information of the study as well as patient, intervention, comparison, and outcomes of interest data. A random-effects model was used to pool quantitative data from the primary outcomes. Results: We included 5 clinical trials with a low-moderate risk of bias that reported data for 301 patients. Meta-analysis showed that, at 6 months after the intervention, single and multiple (double or triple) injections had similar pain improvement, with no significant differences (standardized mean difference [SMD], 0.61 [95% CI, −1.09 to 2.31]; I ² = 97%; P = .48). A significant improvement in knee functionality was observed in favor of multiple injections (SMD, 2.29 [95% CI, 0.45-4.12]; I ² = 97%; P = .01). Subanalysis showed that the significant improvement was only evident for the results of single versus triple injections (SMD, 3.12 [95% CI, 0.64-5.60]; I ² = 97%; P = .01). Conclusion: According to our results, a single injection was as effective as multiple PRP injections in pain improvement; however, multiple injections seemed more effective in joint functionality than a single injection at 6 months. We consider that the available evidence is still insufficient, and future research on this specific topic is needed to confirm our results.

In the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial, Marso et al. (July 28 issue)¹ found that persons with type 2 diabetes who were at high risk for cardiovascular events had lower rates of cardiovascular events with liraglutide than with placebo. Although the authors state that liraglutide or placebo was added to “standard care,” a review of baseline cardiovascular medications (Table S4 in the Supplementary Appendix of the article, available at NEJM.org) reveals that patients in the liraglutide group had a significantly higher rate of use of beta-blockers than those in the placebo group (56.8% vs. 54.1%) as well as numerically higher rates of use of angiotensin-converting–enzyme inhibitors (51.8% vs. 50.3%), statins (72.9% vs. 71.4%), and platelet-aggregation inhibitors (68.7% vs. 66.8%). The LEADER trial included patients with established cardiovascular disease and persons with cardiovascular risk factors. Subgroup analysis (Figure 2 of the article) suggests that the cardiovascular benefit of liraglutide was driven by the subgroup of patients with established cardiovascular disease, which is the very population in which cardiovascular medications have shown the most benefit.

Objectives: In the care of patients with type 2 diabetes, self-management is emphasised and studied while theory and observations suggest that patients also benefit from social support. We sought to assess the effect of social network interventions on social support, glycaemic control and quality of life in patients with type 2 diabetes.Research design and methods: We searched Ovid MEDLINE, Ovid EBM Reviews, Cochrane Central Register of Controlled Trials, EMBASE, PsycINFO and CINAHL through April 2017 for randomised clinical trials (RCTs) of social network interventions in patients with type 2 diabetes. Reviewers working independently and in duplicate assessed eligibility and risk of bias, and extracted data from eligible RCTs. We pooled estimates using inverse variance random effects meta-analysis.Results: We found 19 eligible RCTs enrolling 2319 participants. Social network interventions were commonly based on individual behaviour change rather than social or interpersonal theories of self-management, were educational, and sought to engage social network members for their knowledge and experience. Interventions improved social support (0.74 SD (95% CI 0.32 to 1.15), I²=89%, 8 RCTs) and haemoglobin A1c at 3 months (−0.25 percentage points (95% CI −0.40 to -0.11), I²=12%, 9 RCTs), but not quality of life.Conclusions: Despite a compelling theoretical base, researchers have only minimally studied the value of interventions targeting patients’ social networks on diabetes care. Although the body of evidence to date is limited, and based on individual behaviour change theories, the results are promising. This review challenges the scientific community to design and test theory-based interventions that go beyond self-management approaches to focus on the largely untapped potential of social networks to improve diabetes care.PROSPERO registration: CRD42016036117.