Use of glucocorticoids in patients with acute respiratory distress syndrome: a meta-analysis and trial sequential analysis.

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.

Effect of oxygenation modalities among patients with postoperative respiratory failure: a pairwise and network meta-analysis of randomized controlled trials.

BACKGROUND: Postoperative respiratory failure is associated with increased perioperative complications. Our aim is to compare outcomes between non-invasive ventilation (NIV), high-flow nasal cannula (HFNC), and standard oxygen in patients at high-risk for or with established postoperative respiratory failure. METHODS: Electronic databases including PubMed, Embase, and the Cochrane Library were reviewed from inception to September 2019. We included only randomized controlled trials (RCTs) that compared NIV, HFNC, and standard oxygen in patients at high risk for or with established postoperative respiratory failure. We performed a Bayesian network meta-analysis to calculate the odds ratio (OR) and Bayesian 95% credible intervals (CrIs). RESULTS: Nine RCTs representing 1865 patients were included (the mean age was 61.6 ± 10.2 and 64.4% were males). In comparison with standard oxygen, NIV was associated with a significant reduction in intubation rate (OR 0.23; 95% Cr.I. 0.10-0.46), mortality (OR 0.45; 95% Cr.I. 0.27-0.71), and intensive care unit (ICU)-acquired infections (OR 0.43, 95% Cr.I. 0.25-0.70). Compared to standard oxygen, HFNC was associated with a significant reduction in intubation rate (OR 0.28, 95% Cr.I. 0.08-0.76) and ICU-acquired infections (OR 0.41; 95% Cr.I. 0.20-0.80), but not mortality (OR 0.58; 95% Cr.I. 0.26-1.22). There were no significant differences between HFNC and NIV regarding different outcomes. In a subgroup analysis, we observed a mortality benefit with NIV over standard oxygen in patients undergoing cardiothoracic surgeries but not in abdominal surgeries. Furthermore, in comparison with standard oxygen, NIV and HFNC were associated with lower intubation rates following cardiothoracic surgeries while only NIV reduced the intubation rates following abdominal surgeries. CONCLUSIONS: Among patients with post-operative respiratory failure, HFNC and NIV were associated with significantly reduced rates of intubation and ICU-acquired infections compared with standard oxygen. Moreover, NIV was associated with reduced mortality in comparison with standard oxygen.

Effect of Vitamin D Supplementation on the Incidence of Diabetes Mellitus.

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.

Targeted Temperature Management in Cardiac Arrest Patients With an Initial Non-Shockable Rhythm: A Systematic Review and Meta-Analysis.

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.

Optimal timing of coronary intervention in patients resuscitated from cardiac arrest without ST-segment elevation myocardial infarction (NSTEMI): A systematic review and meta-analysis.

OBJECTIVE: Performing immediate coronary angiography (CAG) in patients with a cardiac arrest and a non-ST-elevation myocardial infarction (NSTEMI) remains a highly debated topic. We performed a meta-analysis aiming to evaluate the influence of immediate, delayed, and no CAG in patients with cardiac arrest and NSTEMI. METHODS: A comprehensive literature review of Pubmed/MEDLINE, Cochrane Library, and Embase was performed for all studies that compared immediate CAG to delayed or no CAG in the setting of cardiac arrest and NSTEMI. The primary outcome was long-term mortality and secondary outcomes included short-term mortality and a Cerebral Performance Category (CPC) score of 1-2 at the longest follow-up period. A random-effects model was used to report odds ratios (ORs) with Bayesian 95% credible intervals (CrIs), and ORs with 95% confidence intervals (CIs) for both network and direct meta-analyses, respectively. RESULTS: 11 studies were included in the final analysis: 8 observational, 1 post-hoc analysis and 2 randomized trials, totaling 3702 patients. The mean age was 63.8±12.8 years with 78% males. We found that immediate and delayed CAG were associated with lower long-term mortality when compared to no CAG (OR 0.21; 95% CrI 0.05-0.82) and (OR 0.11; 95% CrI 0.03-0.43), as well as lower short-term mortality (OR 0.17; 95% CrI 0.04-0.64) and (OR 0.07; 95% CrI 0.01-0.29), respectively. In addition, immediate and delayed CAG were associated with a significantly higher number of patients with a CPC score of 1-2 (OR 4.15; 95% CrI 1.10-16.10) and (OR 4.67; 95% CrI 1.53-15.12), respectively. There were no significant differences between immediate or delayed CAG regarding long-term mortality, short-term mortality, or favorable CPC score. CONCLUSIONS: Among patients who survived cardiac arrest with an NSTEMI, CAG is associated with a higher rate of survival and favorable neurological outcomes compared with no CAG. There were no differences between immediate and delayed strategies.

The role of anticoagulation in venous thromboembolism primary prophylaxis in patients with malignancy: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Venous thromboembolism (VTE) is a common cause of morbidity and mortality among patients with cancer. As such, we conducted a meta-analysis of randomized controlled trials (RCTs) that evaluated anticoagulants as primary prophylaxis against VTE in cancer patients. METHODS: Pubmed/MEDLINE, Embase, and the Cochrane Library were screened for all RCTs that used anticoagulation therapy in cancer patients for primary prevention of VTE. The primary outcomes were VTE events. Secondary outcomes included all-cause mortality, VTE-related mortality and major bleeding. A random effects model was used to report the risk ratios (RR) with 95% confidence intervals (CIs), and odds ratios (ORs) with Bayesian 95% credible intervals for both direct and network meta-analyses, respectively. RESULTS: Twenty-four RCTs were included totaling 13,338 patients (7197 received anticoagulation and 6141 received placebo). The mean age ranged between 54.6 and 68.1 years, with 50.5% male. Compared with placebo, low-molecular-weight heparin (LMWH) or direct Xa inhibitors were associated with lower VTE events (RR 0.58; 95%CI 0.48-0.69, P < 0.001) and (RR 0.39; 95%CI 0.24-0.63, p < 0.001), respectively. LMWH was associated with decreased VTE and all-cause mortality when compared with placebo (P < 0.05). Regarding safety outcomes, LMWH and direct Xa inhibitors were not associated with increased risks of major bleeding (P > 0.05) when compared with placebo. Results regarding VTE events and major bleeding were consistent in both lung and pancreatic cancers. CONCLUSIONS: Both LMWH and direct Xa inhibitors were associated with a lower VTE events compared with placebo. However, this potentially protective effect must be balanced against the possible increased risk of bleeding for some patients.

Aspirin Efficacy in Primary Prevention: A Meta-analysis of Randomized Controlled Trials.

INTRODUCTION: The role of aspirin as a means of primary prevention remains controversial. AIM: We have conducted a meta-analysis of all randomized controlled trials (RCTs) to evaluate the role of aspirin in primary prevention. METHODS: Literature search was performed via PubMed, Embase, and the Cochrane Library for all related RCTs. All-cause mortality was the primary endpoint. Secondary endpoints included major adverse cardiovascular events (MACE), myocardial infarction (MI), cardiovascular mortality, cerebrovascular events, and bleeding events. We used a random effects model to report the risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: Our analysis included 17 RCTs (164,862 patients; 83,309 received aspirin and 81,744 received placebo). Our study did not demonstrate any significant reduction in all-cause mortality for patients treated with aspirin when compared with placebo (RR 0.97; 95% CI 0.93-1.01; P = 0.13). Sensitivity analysis performed by excluding healthy elderly (≥ 65) showed significant reductions in all-cause mortality in the aspirin-treated patients (RR 0.94; 95% CI 0.90-0.99; P = 0.01). There were no significant differences between both groups regarding cardiovascular mortality and cerebrovascular events (P > 0.05). However, aspirin-treated patients significantly reduced MACE and MI events (RR 0.89; 95% CI 0.85-0.93; P < 0.001 and RR 0.88; 95% CI 0.78-0.98; P = 0.02, respectively), respectively. However, aspirin was associated with a significantly higher incidence of bleeding, including major bleeding and intracranial bleeding (P < 0.001). CONCLUSIONS: Aspirin use in primary prevention has resulted in a lower incidence of MACE and MI without significantly effecting cerebrovascular events. However, aspirin was associated with a higher bleeding risk. Use of aspirin as a means of primary prevention should be thoroughly discussed with patients and pursued based on the risk of cardiovascular disease while also considering bleeding risk.