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Venous thromboembolism (VTE) is a serious complication of orthopedic surgery. Low molecular weight heparin (LMWH) has been the standard of care for thromboprophylaxis in this population. However, direct oral anticoagulants (DOACs) are increasingly being used as alternatives.To assess the efficacy and safety of DOACs versus LMWH for thromboprophylaxis in orthopedic surgery.We searched MEDLINE, Embase, and the Cochrane Collaboration Central Register of Controlled Trials from inception until April 2020, for randomized controlled trials (RCTs) comparing DOACs with LMWH for thromboprophylaxis in orthopedic surgery.Twenty-five RCTs met inclusion criteria, including 40,438 patients, with a mean age of 68 years and 50% were males. Compared to LMWH, DOACs were associated with a significant reduction of major VTE; defined as the composite events of proximal deep vein thrombosis (DVT), pulmonary embolism (PE), and VTE-related mortality (RR 0.33; 95% CI: 0.20-0.53; P0.01), and total DVT (RR: 0.59; 95% CI: 0.48-0.73; P0.01), but not PE (RR 0.81; 95% CI: 0.49-1.34; P=0.42). There was no statistically significant difference between both groups on the incidence of major bleeding (RR 0.99; 95% CI: 0.77-1.27; P=0.92), clinically relevant non-major bleeding (RR 1.04; 95% CI: 0.92-1.17; P=0.52), all-cause mortality (RR 1.06; 95% CI: 0.64-1.76; P=0.83), VTE-related mortality (RR 0.84; 95% CI: 0.40-1.74; P=0.64) and bleeding-related mortality (RR 1.24; 95% CI: 0.30-5.18; P=0.77).For patients undergoing orthopedic surgery, thromboprophylaxis with DOACs is associated with a significant reduction of major VTE and DVT, compared to LMWH. Safety outcomes were not significantly different between both treatment groups.

Background Cancer associated venous thromboembolism (VTE) results in significant morbidity and mortality. Low molecular weight heparin (LMWH) has been standard of care for treatment of cancer-associated VTE, however direct oral anticoagulants (DOACs) are emerging as alternative treatment options. Objective To compare the benefits and harms of DOACs versus LMWH for treatment of VTE in cancer. Data sources MEDLINE, Embase, and the Cochrane Collaboration Central Register of Controlled Trials from inception to April 2020. Study selection Randomized controlled trials (RCT) comparing DOACs with LMWH for treatment of VTE in cancer patients. Data synthesis Four good-quality RCTs, met inclusion criteria. Compared with LMWH, DOACs were associated with lower rates of VTE recurrence (RR 0.62; 95% CI: 0.44–0.87; P = 0.006), and DVT recurrence (RR 0.61; 95% CI: 0.4–0.94; P = 0.02) but not PE recurrence (RR 0.73; 95% CI: 0.51–1.04; P = 0.08), in cancer patients. However, the risk of clinically relevant non-major bleeding (CRNMB) (RR 1.58; 95% CI: 1.11–2.24; P = 0.01), and major bleeding in gastrointestinal cancer (RR 2.55; 95% CI 1.24–5.27, P = 0.01), were higher with DOACs. The risk of overall major bleeding (RR 1.33; 95% CI: 0.84–2.1; P = 0.22), all-cause mortality (RR 0.99; 95% CI: 0.84–1.17; P = 0.92), VTE-related mortality (RR: 1; 95% CI: 0.29–3.44; P = 1) and bleeding-related mortality (RR: 0.71; 95% CI: 0.17–2.91; P = 0.63), were similar in both treatment groups. Conclusion Among cancer patients with VTE, treatment with DOACs is associated with a significant reduction of VTE and DVT recurrence, compared to LMWH. These benefits were offset by an increased risk of CRNMB, and major bleeding in gastrointestinal cancer.

Critically ill patients (patients treated in a medical or surgical intensive care unit) are at high risk of venous thromboembolism (VTE) development (deep vein thrombosis [DVT] and/or pulmonary embolism). Multiple thromboprophylaxis strategies have been used for the prevention of VTE in this population with various outcomes. Therefore, we aimed to evaluate the efficacy of intermittent pneumatic compression (IPC) prophylaxis in the lower limb compared with no treatment, anticoagulant use, or their combinations in reducing risk. A comprehensive electronic database search was conducted for all randomized clinical trials (RCTs) comparing the clinical outcomes of IPC versus anticoagulants or no treatment or their combinations for the prevention of VTE for critically ill patients. The primary outcome was VTE. The secondary outcome was DVT. We performed a Bayesian network meta-analysis to calculate odds ratios (ORs) and 95% credible intervals (CrIs). We included 5 RCTs with 3133 total patients, represented by a mean age of 49.61 ± 18 years, while 60.28% were male. There was a significant reduction of the primary outcome (incidence of VTE events) when no treatment was compared with IPC (OR = 0.36; 95% CrI = 0.18-0.71), anticoagulation alone (OR = 0.30; 95% CrI = 0.12-0.68), or anticoagulation with IPC (OR = 0.34; 95% CrI = 0.13-0.81). In addition, there was a significant reduction in DVT when no treatment was compared with IPC (OR = 0.45; 95% CrI = 0.21-0.9), anticoagulation alone (OR = 0.16; 95% CrI = 0.03-0.66), or anticoagulation with IPC (OR = 0.18; 95% CrI = 0.03-0.84). However, there were no significant differences between other comparisons (IPC vs anticoagulation alone, anticoagulation alone vs anticoagulation with IPC, or anticoagulation with IPC vs IPC alone) regarding VTE or DVT incidence. Among critically ill patients, IPC alone, anticoagulation alone, and IPC with anticoagulation were associated with a significant reduction of VTE and DVT incidence compared with no treatment. However, there was no significant difference between these modalities when compared together. Therefore, further larger studies comparing those different thromboprophylaxis modalities and their combinations are needed to provide more robust results for future clinical recommendations.

In the United States, cancer is the second leading cause of mortality, and millions more battle cancer worldwide. As such, primary prevention of cancer is a major interest globally. Aspirin has been studied as a primary prevention method for multiple diseases, mainly cardiovascular disease and various forms of cancer. The role of aspirin as a primary prevention of cancer is still controversial and may be more beneficial in certain cancers over others. With rapidly surfacing large randomized controlled trials (RCTs) studying this subject, we aimed to evaluate the efficacy and safety of aspirin as a primary prophylaxis for cancer. A comprehensive electronic database search was conducted for all RCTs that compared aspirin versus placebo for the prevention of any type of disease, and where cancer incidence or mortality was reported. The primary outcome was cancerrelated mortality. Secondary outcomes were cancer incidence, all-cause mortality, major bleeding, any bleeding and gastrointestinal (GI) bleeding. We calculated risk ratios (RRs) and 95% confidence intervals (CIs) using a random-effects model at the longest follow-up period. We included 16 RCTs with 104,018 total patients, mean age of 60.51 years, mean follow-up of 5.48 years, and a male percentage of 38.72%. We found that aspirin was not associated with a significant reduction of cancer-related mortality compared with placebo (RR 0.99; 95% CI: 0.87–1.12; P = 0.85: I2 = 41%). Compared with placebo, aspirin was not associated with significant reduction of all-cause mortality (RR 0.97; 95% CI: 0.92–1.02; P = 0.19; I2 = 13%) or cancer incidence (RR: 0.98; 95% CI: 0.92–1.04; P = 0.43; I2 = 16%). However, aspirin treatment was associated with significantly increased risks of any bleeding (RR 1.63; 95% CI: 1.31–2.03; P < 0.01), major bleeding (RR 1.41; 95% CI: 1.26–1.57; P < 0.01), and GI bleeding (RR 1.85; 95% CI: 1.38–2.48; P < 0.01) compared with placebo. Our study did not find any significant reductions in cancer-related mortality or cancer incidence when compared aspirin use with placebo or no aspirin. Our study also highlights that the use of aspirin for primary prevention of cancer was found to cause higher rates of bleeding (any bleeding, major bleeding, and GI bleeding) compared to placebo or no aspirin at the longest follow-up period with no significant benefit in cancer primary prevention.

BackgroundPostoperative 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.MethodsElectronic 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).ResultsNine 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.ConclusionsAmong 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.

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.