Singh, Balwinder

Abstract Objective The aim of this study was to evaluate the efficacy and safety of the dopaminergic‐enhancing agent modafinil/armodafinil (MoArm) as adjunctive treatment for bipolar depression. Methods A comprehensive search of major electronic databases was conducted to identify randomized controlled trials (RCTs) of adjunctive MoArm that included patients with bipolar I (BP‐I) or bipolar II (BP‐II) depression. Data for response/remission and all‐cause discontinuation were analyzed. Effect size was summarized by relative risk (RR) using a random effect model. Results Of 58 studies, five RCTs (N = 795 drug, N = 792 placebo) met inclusion criteria. Four armodafinil studies included only BP‐I patients and one modafinil study included both bipolar subtypes with limited heterogeneity ( I 2 = 34%, P = .19; I 2 = 18%, P = .30). Compared to placebo, augmentation with MoArm was associated with significantly greater rates of treatment response (RR, 1.18; 95% CI, 1.01‐1.37; P = .03) and remission (RR, 1.38; 95% CI, 1.10‐1.73; P = .005). All‐cause discontinuation was not different than placebo (RR, 1.08; 95% CI, 0.89‐1.30; P = .45) with no evidence of increased risk of mood switch or suicide attempts with MoArm (RR, 0.99; 95% CI, 0.39‐2.5; P = .98; RR, 1.02; 95% CI, 0.37‐2.85; P = .97). Conclusion This narrower scope meta‐analysis of one drug for one disease suggests that adjunctive MoArm may represent a novel therapeutic intervention. Further studies delineating the subtypes of bipolar depression responsive to these novel dopaminergic‐enhancing agents are encouraged.

BACKGROUND: The use of β 2 agonist as an intervention for acute lung injury (ALI) and ARDS patients is controversial, so we performed a systematic review and meta-analysis of the published randomized controlled trials of using β 2 agonists to improve outcomes (mortality and ventilator free days) among patients with ALI/ARDS. METHODS: A comprehensive search of 7 major databases (Ovid MEDLINE In-Process and other non-indexed citations, Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials (CENTRAL), Ovid Cochrane Database of Systematic Reviews, Web of Science, and Scopus) for randomized controlled trials using β 2 agonists for ALI from their origin to March 2013 was conducted. The effect size was measured by relative risk for dichotomous outcomes, and mean difference for continuous outcomes, with 95% CI. The statistical heterogeneity between the studies was assessed with the Cochran Q test and I 2 statistic. The heterogeneity of > 50% was considered significant for the analysis. The Cochrane risk of bias tool was used to ascertain the quality of the included studies. RESULTS: Out of 219 studies screened, 3 randomized controlled trials reported mortality and ventilator-free days, in 646 ALI/ARDS subjects. Of the 646 subjects, 334 (51.7%) received β 2 agonist and 312 (48.3%) received placebo. There was no significant decrease in 28-day mortality or hospital mortality in the β 2 -agonist group: relative risk 1.04, 95% CI 0.50–2.16, and relative risk 1.22, 95% CI 0.95–1.56, respectively. The ventilator-free days and organ-failure-free days were significantly lower for the ALI subjects who received β 2 agonists: mean difference −2.19 days (95% CI −3.68 to −1.99 d) and mean difference −2.04 days (95% CI −3.74 to −0.35 d), respectively. CONCLUSIONS: In subjects with ALI/ARDS, β 2 agonists were not only nonbeneficial in improving the survival, but were harmful and increased morbidity (reduced organ-failure-free days and ventilator-free days). The current evidence discourages the use of β 2 agonist in ALI/ARDS patients. (International Prospective Register of Systematic Reviews, http://www.crd.york.ac.uk/prospero , 2012:CRD42012002616.)

Objectives To perform a systematic review and meta-analysis including all the current studies to assess the accuracy of pulmonary embolism rule-out criteria (PERC) in ruling out pulmonary embolism (PE). Methods We conducted a comprehensive search of the major databases (Ovid Medline In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid PsycInfo, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews and Scopus) and references of potentially eligible articles and conference proceedings of major emergency medicine organisations through May 2012. We included all original research studies conducted in emergency departments on diagnostic performance of PERC. Two reviewers independently identified the eligible studies and extracted data. Sensitivity, specificity and likelihood ratios were calculated using contingency tables. Results 12 studies including 13 cohorts (three retrospective, 10 prospective) were included, comprising of 14 844 patients from six countries. 12 cohorts were urban and one was rural. Pooled (95% CI) sensitivity, specificity, positive and negative likelihood ratio were 0.97 (0.96 to 0.98), 0.22 (0.22 to 0.23), 1.22 (1.16 to 1.29) and 0.17 (0.13 to 0.23), respectively. The pooled (95% CI) diagnostic OR was 7.4 (5.5–9.8). On meta-regression analysis, there was no significant difference between PE prevalence and PERC diagnostic performance (coefficient (SE) of −0.032 (0.022), p=0.173) or on relative diagnostic OR (0.97, 95% CI 0.92 to 1.02). Significant heterogeneity was observed in specificity (I2=97.4%) and positive likelihood ratio (I2=89.1%). Conclusions Because of the high sensitivity and low negative likelihood ratio, PERC rule can be used confidently in clinically low probability population settings.