Abstract Context The effect of vitamin D supplementation on the risk of type 2 diabetes mellitus (T2DM) remains controversial because most randomized controlled trials (RCTs) have been small or have reported low doses of vitamin D. Objective To conduct a meta-analysis of RCTs testing vitamin D supplementation in the prevention of T2DM. Data Sources Database search of PubMed/MEDLINE, EMBASE, and the Cochrane Library was performed by 2 reviewers from inception through September 15, 2019. Study Selection We included RCTs that reported the effect of vitamin D supplementation for at least 1 year on T2DM prevention. Data Extraction Two independent reviewers extracted the data. The risk ratios (RRs) and 95% confidence intervals (CIs) were reported. Primary outcome of the meta-analysis was the incidence of T2DM. Data Synthesis Nine RCTs were included (43 559 participants). The mean age (standard deviation) was 63.5 (6.7) years. The RR for vitamin D compared with placebo was 0.96 (95% CI, 0.90-1.03); P = 0.30. In trials testing moderate to high doses of supplementation (≥1000 IU/day), all conducted among participants with prediabetes, the RR for vitamin D compared with placebo was 0.88 (95% CI, 0.79-0.99). In contrast, the trials testing lower doses, which were conducted in general population samples, showed no risk reduction (RR, 1.02; 95% CI, 0.94-1.10; P, interaction by dose = 0.04). Conclusion In patients with prediabetes, vitamin D supplementation at moderate to high doses (≥1000 IU/day), significantly reduced the incidence risk of T2DM, compared with placebo.

Background: Acute respiratory distress syndrome (ARDS) is a common and disabling disease with high rates of mortality and morbidity. The role of steroids in treating ARDS remains controversial. We aim to examine the evidence behind using glucocorticoids in the management of ARDS from the available studies. Methods: We performed a literature review of major electronic databases for randomized controlled trials (RCTs) comparing glucocorticoids versus placebo in treating patients with ARDS. Our primary outcome was hospital mortality. Other outcomes included ICU mortality, number of ventilator-free days at day 28, incidence of nosocomial infections, and hyperglycemia. We performed a meta-analysis using a random effects model to calculate risk ratios (RR) and mean difference (MD) with their corresponding 95% confidence intervals (CI). A subsequent trial sequential analysis was performed to examine the strength of evidence and to guard against statistical type I and type II errors for our results. Results: Eight RCTs were included in the final analysis totaling of 1091 patients, with a mean age of 57 ± 16, and 56.2% were male. In our pooled analysis, use of glucocorticoids was associated with a significant reduction in hospital mortality (RR 0.79; 95% CI 0.64-0.98; P = 0.03) and ICU mortality (RR 0.64; 95% CI 0.42-0.97; P = 0.04). Furthermore, glucocorticoid use was associated with an increased number of ventilator-free days at day 28 (MD 4.06 days; 95% CI 2.66-5.45; P < 0.01). Regarding adverse events, glucocorticoids use was not associated with an increased risk for nosocomial infections (RR 0.82; 95% CI 0.68-1.00; P = 0.05); however, it was associated with an increased risk of hyperglycemia (RR 1.11; 95% CI 1.01-1.24; P = 0.04). In our trial sequential analysis, the required diversity-adjusted information size (sample size = 2692 patients) was not reached, and the evidence was insufficient from the available RCTs. Conclusion: Among patients with ARDS, use of glucocorticoids is associated with a significant reduction in mortality and duration of mechanical ventilation, without increased risk of hospital-acquired infections. However, based on a trial sequential analysis, these findings may be secondary to a false-positive (type I) error. Further studies are needed for a firm conclusion with guarding against possible statistical errors.

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Background: Targeted temperature management (TTM) is now recommended for patients presenting with an out-of-hospital cardiac arrest. However, there are limited data that support its use in patients with an initial non-shockable rhythm (NSR). Methods: A literature search of PubMed/MEDLINE, Cochrane Library, and Embase was conducted by two independent authors for studies that compared TTM along with standard care versus standard care alone in treating cardiac arrest with initial NSR. Outcomes were short-term and long-term survival, and a Cerebral Performance Category (CPC) score of 1 to 2 at the longest follow-up period. The Mantel-Haenszel random-effects model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Trial sequential analysis (TSA) was performed on the randomized controlled trials (RCTs). Results: Thirty studies were included in the final analysis: 25 observational and five RCTs, totalling 10,703 patients, 4,023 of whom received TTM and 6,680 received standard care alone. Compared with standard care, patients who presented with an initial NSR cardiac arrest and received TTM (target of 32°C –34°C) had a significantly higher short-term survival (OR 1.44 95% CI 1.15–1.81; P = 0.002), long-term survival (OR 1.52 95% CI 1.03–2.26; P = 0.04), and CPC score of 1 to 2 (OR 1.63 95% CI 1.22–2.17; P = 0.0010). Sensitivity analyses by including only RCTs showed a trend, although not significant, toward better short-term survival (OR 1.25 95% CI 0.82–1.89; P = 0.30), long-term survival (OR 1.15 95% CI 0.80–1.66; P = 0.46), and neurologic outcomes (OR 1.51 95% CI 0.81–2.80; P = 0.19). However, TSA performed on the RCTs revealed that the results were inconclusive. Conclusion: Among patients who survived cardiac arrest with an initial NSR, TTM is associated with a higher rate of survival and favorable neurological outcomes compared with no TTM. However, analyses from the included RCTs did not support this conclusion.