Aims The aim of this study was to determine whether gonadotropin-releasing hormone (GnRH) antagonists (an emerging class of drugs to suppress testosterone synthesis in the treatment of prostate cancer) cause less adverse cardiovascular events than the more commonly use GnRH agonists. Methods and Results We conducted a systematic review to identify all randomised, controlled trials in which a GnRH antagonist was compared with a GnRH agonist in men with prostate cancer. We identified ten eligible studies including two different GnRH antagonists, degarelix (n = 1681) and relugolix (n = 734), which were compared with the GnRH agonists, leuprolide (n = 714) and goserelin (n = 600). The pooled risk ratios (95% confidence intervals) among GnRH antagonist recipients for adverse cardiovascular events, cardiovascular death and all-cause mortality were 0.57 (0.39-0.81); 0.49 (0.25-0.96); and 0.48 (0.28-0.83) respectively. Important limitations of the included trials were their short duration of follow-up, unblinded study design and (in most of the studies) the identification of adverse cardiovascular events through safety reporting mechanisms rather than as a pre-specified outcome. There was no evidence of heterogeneity of findings among the studies. Conclusions There is consistent but methodologically limited data to suggest that GnRH antagonists – a relatively new class of androgen deprivation therapy for prostate cancer – cause significantly less cardiovascular adverse effects than the more frequently used GnRH agonists.

Delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage is a cause of considerable morbidity and mortality. Magnesium sulfate has been proposed as a prophylactic intervention for angiographic vasospasm and to improve clinical outcomes. A systematic review was conducted to determine the evidence for the prophylactic use of magnesium sulfate in aneurysmal subarachnoid hemorrhage. Medline, Embase, Cochrane library, clinicaltrials.gov, and controlled-trials.com were searched with a comprehensive search strategy. 2,035 records were identified in the initial search and 1,574 remained after removal of duplicates. Randomized, parallel group, controlled trials of magnesium sulfate in patients with aneurysmal subarachnoid hemorrhage were included. A total of ten studies were included. Review Manager and GRADE software were used to synthesize the results. The summary effect for Glasgow outcome scale and the modified Rankin scale is a risk ratio (RR) of 0.93 [95 % confidence interval (CI) 0.82-1.06]. The RR for mortality is 0.95 [95 % CI 0.76-1.17]. Delayed cerebral ischemia has a RR of 0.54 [95 % CI 0.38-0.75], which is the only outcome with a statistically significant summary effect measure favoring magnesium treatment. Delayed ischemic neurological deficit has a RR of 0.93 [95 % CI 0.62-1.39]. Transcranial doppler vasospasm has a RR of 0.72 [95 % CI 0.51-1.03]. Current evidence does not support the prophylactic use of magnesium sulfate in aneurysmal subarachnoid hemorrhage.

Among children, neonates have the highest incidence of thrombosis due to risk factors such as catheter instrumentation, an evolving coagulation system and congenital heart disease. Low-molecular-weight heparins (LMWHs) are the most commonly used anticoagulants in neonates. Published guidelines delineate dosing and monitoring protocols for LMWH therapy in newborns. However, challenging clinical situations frequently present that warrant healthcare providers to think critically beyond the range of guidelines, and judiciously resolve specific problems. This review describes the use of LMWH in the neonatal population, including practical aspects such as route and site of administration, preparation from concentrated formulations and methods to minimize pain of subcutaneous injection. It is followed by a discussion on dosing, monitoring and outcomes of LMWH therapy in neonates. The risk of recurrence of thrombosis in neonates after LMWH therapy is approximately 3% based on a pooled analysis of studies reporting this outcome over the last 24 years. The article concludes with an overview of the side-effects of LMWH, including the risk of bleeding which is around 4% based on pooled analyses of more than 30 studies.

This systematic review summarizes the outcome reporting standards in Dupuytren’s disease treatment research. A search of Ovid Medline, Ovid Embase, and CINAHL was conducted. Randomized controlled trials, cohort studies, and case series published between 1997 and 2017, investigating treatment of Dupuytren’s disease with fasciectomy, fasciotomy, or collagenase, were eligible for inclusion. Range of motion was the most commonly reported outcome, appearing in 77% of included studies. Outcomes, such as range of motion, recurrence, and clinical success, were frequently defined, however many different definitions were used. We identified 37 unique measurement methods for range of motion, 28 for recurrence, and 25 for clinical success. Most outcomes were assessed at multiple time points, and only a few studies reported results according to established clinical significance thresholds. Development of a core outcome set will help standardize outcome reporting, and ensure future research in this field is relevant, interpretable, and amenable to systematic review and/or meta-analysis.

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