Meta-analysis of optimal timing of coronary intervention in non-ST-elevation acute coronary syndrome.

OBJECTIVES: We conducted a meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of early versus delayed invasive management of non-ST-elevation acute coronary syndrome (NSTE-ACS). BACKGROUND: Coronary angiography is recommended for patients with NSTE-ACS, however, the optimal timing for this remains controversial. METHODS: Literature search of Pubmed/MEDLINE, Cochrane Library, and Embase for all RCTs that compared early with delayed invasive approaches in treating NSTE-ACS was conducted by two independent authors. Primary outcome was major adverse cardiovascular events (MACE), while the secondary outcomes included cardiovascular mortality, all-cause mortality, myocardial infarction (MI), and bleeding events. The Mantel-Haenszel random-effects model was used to calculate risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: We included 14 RCTs (9,637 patients, mean age 65.4, 67% males). The early invasive strategy was associated with a lower incidence of MACE compared with the delayed invasive strategy (RR 0.65, 95%CI 0.49-0.87; p = .003). Subgroup analysis according to GRACE score showed a lower incidence of MACE with early invasive strategies in GRACE >140 patients (p for interaction = .002). Furthermore, recurrent ischemia was lower in patients with an early invasive strategy (RR 0.42, 95%CI 0.26-0.69; p < .0005). In contrast, there were no significant differences in all-cause mortality, cardiovascular mortality, MI, or bleeding events between groups (all p > .05). CONCLUSIONS: Among patients with NSTE-ACS, an early invasive strategy was associated with lower incidence of MACE and recurrent ischemia compared with delayed invasive strategy. There were no significant differences in all-cause mortality, cardiovascular mortality, MI, or bleeding events between groups.

Noninvasive Oxygenation Strategies in Immunocompromised Patients With Acute Hypoxemic Respiratory Failure: A Pairwise and Network Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Acute hypoxemic respiratory failure (AHRF) is a leading cause of intensive care unit (ICU) admission among immunocompromised patients. Invasive mechanical ventilation is associated with increased morbidity and mortality. OBJECTIVE: To evaluate the efficacy of various oxygenation strategies including noninvasive ventilation (NIV), high-flow nasal cannula (HFNC), and conventional oxygen therapy in immunocompromised patients with AHRF. METHODS: Electronic databases including PubMed, Embase, and the Cochrane Library were reviewed from inception to December 2018. We included all randomized controlled trials (RCTs) comparing different modalities of initial oxygenation strategies in immunocompromised patients with AHRF. Our primary outcome was the need for intubation and invasive mechanical ventilation while secondary outcomes were ICU acquired infections and short- and long-term mortality. Data were extracted separately and independently by 2 reviewers. We performed a Bayesian network meta-analysis to calculate odds ratio (OR) and Bayesian 95% credible intervals (CrIs). RESULTS: Nine RCTs were included (1570 patients, mean age 61.1 ± 13.8 years with 64% male). Noninvasive ventilation was associated with a significantly reduced intubation rate compared with standard oxygen therapy (OR: 0.53; 95% CrI: 0.26-0.91). There were no significant reductions of intubation between NIV versus HFNC (OR: 0.83; 95% CrI: 0.35-2.11) or HFNC versus standard oxygen therapy (OR: 0.65; 95% CrI: 0.26-1.24). There were no significant differences between all groups regarding short-term (28-day or ICU) mortality or long-term (90-day or hospital) mortality or ICU-acquired infections (P > 0.05). CONCLUSION: Among immunocompromised patients with AHRF, NIV was associated with a significant reduction of intubation compared with standard oxygen therapy. There were no significant differences among all oxygenation strategies regarding mortality and ICU-acquired infections.

Comparison of racial distribution of photodermatoses in USA academic dermatology clinics: A multicenter retrospective analysis of 1080 patients over a 10-year period.

BACKGROUND: Previous studies at single academic institutions have identified variations in the prevalence of photodermatoses among racial groups. The purpose of the study was to compare the distribution of photodermatoses between Whites and Blacks at four academic medical centers in the USA. METHODS: A retrospective chart review was performed at four institutions' general dermatology clinics using diagnoses consistent with the International Classification of Disease (ICD), Ninth and Tenth Revisions, codes related to photodermatoses between August 2006 and August 2016. A total of 9736 charts were manually reviewed and classified. Analyses were performed analyzing the frequency of photodermatoses between Whites and Blacks in the pooled data. RESULTS: There were 1,080 patients with photodermatoses identified. Statistically significant differences in the frequency of photodermatoses between Whites and Blacks were identified for polymorphous light eruption (more common in Blacks), photoallergic contact dermatitis, phototoxic drug eruption, phytophotodermatitis, porphyria, and solar urticaria (more common in Whites). The most commonly diagnosed photodermatoses were polymorphous light eruption (total 672), and photodermatitis not otherwise specified (total 189). CONCLUSION: Our study demonstrated significantly higher proportions of polymorphous light eruption in Blacks, and higher proportions of photoallergic contact dermatitis, phototoxic drug eruptions, phytophotodermatitis, porphyrias, and solar urticaria in Whites.

Extended duration of thromboprophylaxis for medically ill patients: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: The benefit of extended-duration thromboprophylaxis in patients hospitalised for acute medical illness beyond hospital stay remains controversial. AIMS: To perform a meta-analysis of randomised controlled trials (RCT) in order to examine the efficacy and safety of extended-duration anticoagulation for venous-thromboembolism (VTE) prophylaxis in this high-risk population. METHODS: An electronic database search was conducted to include all RCT comparing between extended-duration versus short-duration prophylactic anticoagulation in medically ill patients. The primary efficacy outcome was the composite events of asymptomatic deep vein thrombosis (DVT), symptomatic VTE and death from VTE-related causes. RESULTS: Five RCT were included totalling 40 124 patients, with a mean age of 71 years and 51% were male. In comparison to standard-duration therapy, extended-duration thromboprophylaxis was associated with a significant reduction in the primary efficacy outcome (risk ratio (RR) 0.75; 95% confidence interval (CI) 0.67-0.85; P < 0.01), symptomatic VTE (RR 0.53; 95% CI 0.33-0.84; P < 0.01) and asymptomatic DVT (RR 0.81; 95% CI 0.71-0.94; P < 0.01). However, there were no significant differences between both groups with regard to VTE-related death (RR 0.81; 95% CI 0.60-1.10; P = 0.18) or all-cause death (RR 0.97; 95% CI 0.88-1.08; P = 0.64). In contrast, extended-duration thromboprophylaxis was associated with an increased risk of major bleeding (RR 2.04; 95% CI 1.42-2.91; P < 0.01) and non-major clinically relevant bleeding (RR 1.81; 95% CI 1.29-2.53; P < 0.01). CONCLUSIONS: Among hospitalised medically ill patients, prolonging venous thromboprophylaxis was associated with a decreased risk of composite events of the primary efficacy outcome and increased risk of bleeding with no significant difference in VTE-related death.

Personalized antiplatelet therapy in patients with coronary artery disease undergoing percutaneous coronary intervention: A network meta-analysis of randomized clinical trials.

OBJECTIVES: This study aimed to evaluate the efficacy and safety of genotype- and phenotype-guided intensified antiplatelet therapy compared with conventional therapy in patients undergoing stent implantation. BACKGROUND: Although potent P2Y12 receptor inhibitors are recommended for percutaneous coronary intervention (PCI)-treated acute coronary syndrome, their usage is limited by a high bleeding risk. Therefore, personalized antiplatelet therapy could provide a valuable foundation for selection of antiplatelet therapy in this population. METHODS: We conducted a Bayesian network meta-analysis for all randomized clinical trials (RCTs) that evaluated genotype- and/or phenotype-guided therapy in PCI-treated coronary artery disease. RESULTS: Thirteen RCTs were included with a total of 6,845 patients. The results showed no significant differences in major adverse cardiovascular events (MACE) between the treatment options ((genotype guided vs. standard of care; OR 0.64; 95% CI: 0.38-1.05) and (phenotype vs. standard of care; OR 0.93; 95% CI: 0.54-1.37)). In addition, no significant differences were demonstrated in bleeding events ((genotype guided vs. standard of care; OR 0.73; 95% CI: 0.45-1.25) and (phenotype vs. standard of care; OR 0.90; 95% CI: 0.62-1.39)). CONCLUSIONS: In this mixed treatment meta-analysis of RCTs, neither genotype- nor phenotype-guided antiplatelet therapy in patients with PCI-treated coronary artery disease was superior to conventional therapy.

CYP2C19 pharmacogenetics versus standard of care dosing for selecting antiplatelet therapy in patients with coronary artery disease: A meta-analysis of randomized clinical trials.

OBJECTIVES: This study aimed to evaluate the efficacy and safety of personalized genotype-guided selection of antiplatelet therapy versus standard of care in patients undergoing percutaneous coronary intervention (PCI). BACKGROUND: Clopidogrel is the most frequently used P2Y12 receptor antagonist in patients with coronary artery disease. However, genetic variations of clopidogrel are associated with inter-individual response variability which could limit its efficacy. METHODS: Electronic databases were searched for all randomized clinical trials (RCTs) evaluating genotype-guided therapy versus standard of care in patients undergoing stent implantation. Aggregated risk ratios (RRs) and 95% CIs were calculated using a random-effects model. RESULTS: We included 6 RCTs with a total of 2,371 patients. When compared with standard of care, the use of genotype-guided therapy did not significantly reduce major adverse cardiovascular events (MACE) (RR 0.67; 95% CI: 0.35-1.27; P = 0.22). However, MACE was significantly reduced in the subset of trials which enrolled only acute coronary syndromes (ACS) (P < 0.01). In addition, there was a significant reduction in myocardial infarction in the genotype-guided group (RR 0.44; 95% CI: 0.28-0.70; P < 0.01; I2 = 0%). Other clinical outcomes were not significantly different: cardiovascular mortality (RR 0.68; 95% CI: 0.27-1.74; P = 0.42), stroke (RR 0.62; 95% CI: 0.23-1.65; P = 0.34), stent thrombosis (RR 0.37; 95% CI: 0.13-1.06; P = 0.06), and bleeding (RR 0.68; 95% CI: 0.43-1.06; P = 0.09). CONCLUSION: In patients undergoing stent implantation, MACE with genotype-guided therapy was not significantly reduced; however, there was a signal towards reduction of MACE in ACS patients, as well as a lower rate of MI, though this will require further confirmation in adequately powered trials.

Clopidogrel and aspirin after ischemic stroke or transient ischemic attack: an updated systematic review and meta-analysis of randomized clinical trials.

Recurrent stroke is common immediately following a transient ischemic attack (TIA) or ischemic stroke. Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin may provide greater protection against subsequent stroke than monotherapy. Electronic databases were searched for randomized clinical trials (RCTs) comparing DAPT with monotherapy in ischemic stroke/TIA. Sixteen RCTs with a total of 29,032 patients were included. Compared with monotherapy, DAPT was associated with significantly lower rates of any stroke (risk ratio [RR] 0.80; 95% confidence interval [CI] 0.72-0.89) and ischemic stroke (RR 0.75; 95% CI 0.66-0.85) during any follow-up period. Although significant increases in intracranial bleeding (RR 1.55; 95% CI 1.20-2.01) and major bleeding (RR 1.90; 95% CI 1.33-2.72) were associated with DAPT, especially with long-term follow-up, the number needed to harm was 258 and 113, respectively. Nevertheless, short-duration DAPT (≤ 1 month) started during the early acute ischemic phase was associated with less bleeding than longer DAPT and greater reduction of recurrent strokes compared with monotherapy. In contrast, long DAPT and DAPT started later after the index event (≥ 1 month) were associated with similar rates of any stroke and increased risks of bleeding compared with monotherapy. Other clinical outcomes were essentially similar between the two groups and included recurrent TIA (RR 0.88; 95% CI 0.72-1.07), myocardial infarction (RR 1.04; 95% CI 0.84-1.29), vascular death (RR 0.99; 95% CI 0.82-1.19), and any death (RR 1.12; 95% CI 0.88-1.42). Similar findings were observed in patients who presented with minor stroke/TIA. Conclusions: Among patients who presented with ischemic stroke/TIA, short-course clopidogrel plus aspirin immediately following the index event appears to be more effective than and as safe as monotherapy for secondary stroke prevention.

Epac1 agonist decreased inflammatory proteins in retinal endothelial cells, and loss of Epac1 increased inflammatory proteins in the retinal vasculature of mice.

PURPOSE: Increased inflammatory mediator levels are reported in diabetic retinopathy. We previously reported that ß-adrenergic receptor agonists reduced inflammatory mediators in the diabetic retina; however, these agents cannot be given systemically. Here, we investigated whether Epac1 is key to the protective effects of ß-adrenergic receptor agonists. METHODS: We cultured primary human retinal endothelial cells (RECs) in normal (5 mM) or high (25 mM) glucose and treated them with an Epac1-specific agonist. Additionally, we generated Epac1 conditional vascular endothelial cell knockout mice by breeding Epac1 floxed mice with Cdh5 Cre mice to investigate the role of Epac1 in the retinal levels of tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß), nuclear factor kappa beta (NFκB), and inhibitor of kappa beta (IκB). Confocal microscopy was performed to localize Epac1 in the mouse retina. RESULTS: Data showed that high glucose increased the TNF-α and IL-1ß levels in the RECs, which were reduced cells treated with the Epac1 agonist. The loss of Epac1 in the retinas of the conditional knockout mice resulted in statistically significantly increased levels of TNF-α and IL-1ß, as well as NFκB. CONCLUSIONS: These data indicate that Epac1 may be protective to the retina through inhibition of key inflammatory mediators.

ß-Adrenergic receptor agonist, compound 49b, inhibits TLR4 signaling pathway in diabetic retina.

Diabetic retinopathy has recently become associated with complications similar to chronic inflammatory diseases. Although it is clear that tumor necrosis factor-α is increased in diabetes, the role of innate immunity is only recently being investigated. As such, we hypothesized that diabetes would increase Toll-like receptor 4 (TLR4) signaling, which could be inhibited by a ß-adrenergic receptor agonist (Compound 49b) previously shown to have anti-inflammatory actions. In order to investigate ß-adrenergic receptor signaling and TLR4 in the diabetic retina, streptozotocin-injected diabetic mice, as well as human primary retinal endothelial cells (RECs) and rat retinal Müller cells (rMC-1) exposed to high glucose (25 mM), were treated with a novel ß-adrenergic receptor agonist, Compound 49b (50 nM), or phosphate-buffered saline (control). TLR4 and its downstream signaling partners (MyD88, IL-1 receptor-associated kinase 1, TNF receptor-associated factor 6 and total and phosphorylated nuclear factor-κB) were examined. In addition, we assessed high-mobility group box 1 (HMGB1) protein levels. Our data showed that diabetes or high-glucose culture conditions significantly increased TLR4 and downstream signaling partners. Compound 49b was able to significantly reduce TLR4 and related molecules in the diabetic animal and retinal cells. HMGB1 was significantly increased in RECs and Müller cells grown in high-glucose culture conditions, which was subsequently reduced with Compound 49b treatment. Our findings suggest that high glucose may increase HMGB1 levels that lead to increased TLR4 signaling. Compound 49b significantly inhibited this pathway, providing a potential mechanism for its protective actions.

Interventions for Secondary Mitral Regurgitation in Patients With Heart Failure: A Network Meta-Analysis of Randomized Controlled Comparisons of Surgery, Medical Therapy and Transcatheter Intervention.

BACKGROUND: Mitral regurgitation (MR) in heart failure (HF) notoriously carries a poor prognosis. While there are multiple interventional options for treatment, the optimal intervention remains controversial. Therefore, we aimed to evaluate the efficacy and safety of surgery, medical therapy, and transcatheter intervention in secondary MR. METHODS: A systematic database search was performed to identify all randomized controlled trials (RCTs) that evaluate various interventions for secondary MR. We performed a Bayesian network meta-analysis to calculate odd ratios (ORs) and 95% credible intervals (CIs). The primary endpoint was all-cause mortality. Secondary endpoints were moderate-severe MR, HF-hospitalizations, and freedom from severe HF symptoms. RESULTS: We identified 12 RCTs (2316 total patients; age 67.6 ±â€¯11; 63% males, and 74% with ischemic cardiomyopathy). There was a significant reduction of mortality at 24-months with transcatheter leaflet repair compared with medical therapy (OR = 0.57; 95% CI = 0.34-0.96). However, there were no significant differences among the competing treatments in all-cause mortality at the earlier time points of 30-days or 12-months (P > 0.05). Recurrent moderate-severe MR was significantly less with valvular interventions compared with medical therapy (P < 0.05), but there were no differences in the rates of HF-hospitalizations or persistent severe HF symptoms between the competing interventions (P > 0.05). CONCLUSIONS: Among patients with HF and secondary MR, transcatheter leaflet repair was associated with significantly reduced 24-month mortality compared with medical therapy. Valvular interventions were associated with lower rates of recurrent moderate-severe MR, but non-significant improvements in clinical outcomes. Further long-term studies are needed to identify the best route of intervention for secondary MR.

Initial Noninvasive Oxygenation Strategies in Subjects With De Novo Acute Hypoxemic Respiratory Failure.

BACKGROUND: De novo hypoxemic respiratory failure is defined as significant hypoxemia in the absence of chronic lung disease such as COPD, and excluding respiratory failure occurring in the immediate postoperative or postextubation period. We aimed to evaluate the efficacy of various oxygenation strategies including noninvasive ventilation (NIV), high-flow nasal cannula (HFNC), and conventional oxygen therapy in patients with de novo hypoxemic respiratory failure. METHODS: We performed electronic database searches of PubMed, Cochrane Library, and Embase from inception to December 2018 to include randomized controlled trials that compared various oxygenation strategies in cases of de novo hypoxemic respiratory failure occurring in adult subjects without a preexisting chronic lung disease and excluding respiratory failure in the immediate postoperative or postextubation periods. We performed a Bayesian network meta-analysis to calculate odds ratio (OR) and Bayesian 95% credible intervals (CrI). RESULTS: 16 studies were included, involving 2,180 subjects with a mean age of 61 ± 17 y (66% were male; 46% of the included subjects were treated with conventional oxygen, 27.8% were treated with NIV, and 25.8% were treated with HFNC). Compared to conventional oxygen, NIV was associated with reduced intubation rates (OR 0.42, 95% CrI 0.26-0.62) but no significant reduction in short-term (OR 0.73, 95% CrI 0.47-1.02) or long-term mortality (OR 0.60, 95% CrI 0.29-1.06). There was no significant difference between NIV and HFNC or between HFNC and conventional oxygen regarding all outcomes. In a sensitivity analysis, the results remained consistent after exclusion of studies that included subjects with respiratory failure secondary to cardiogenic pulmonary edema. CONCLUSION: Among subjects with hypoxemic respiratory failure, NIV was associated with a significant reduction in intubation rates but not short- or long-term mortality when compared to conventional oxygen therapy. There was no significant difference between NIV and HFNC or between HFNC and conventional oxygen regarding all outcomes.

Erratum to "Aspirin for venous thromboembolism prophylaxis after hip or knee arthroplasty: An updated meta-analysis of randomized controlled trials": [J. Orthop. 16 (2019) 312-319].

[This corrects the article DOI: 10.1016/j.jor.2019.02.032.].

Aspirin for venous thromboembolism prophylaxis after hip or knee arthroplasty: An updated meta-analysis of randomized controlled trials.

BACKGROUND: Patients who undergo knee or hip arthroplasty are at a significant risk of venous thromboembolism (VTE) development (pulmonary embolism and/or deep-vein thrombosis). Many different thromboprophylactic strategies have been used for the prevention of VTE in these patients with different outcomes. Therefore, our aim was to evaluate the efficacy and safety of aspirin prophylaxis when compared with placebo or anticoagulants in this population of patients. METHODS: A comprehensive electronic database search was conducted for all randomized controlled trials (RCTs) comparing the clinical outcomes of aspirin versus placebo or anticoagulants for the prevention of VTE after knee or hip arthroplasty. The primary outcome was VTE incidence. Secondary outcomes included any bleeding, major bleeding and mortality. We calculated risk ratios (RRs) and 95% confidence intervals (CIs) using a random-effects model at the longest possible follow-up period. RESULTS: We included 13 RCTs with a total of 20,115 patients with a mean age of 67.15 ±â€¯9.54 and 24.39% males. Aspirin was found to be associated with a non-significantly reduced VTE events compared with other thromboprophylactic methods (RR 0.87; 95% CI: 0.61-1.23; P = 0.43). Compared with placebo, aspirin was associated with significant reduction of VTE (RR 0.65; 95% CI: 0.47-0.89; P = 0.008). There were no significant differences in the clinical outcomes between all groups with regard to mortality (RR 0.98; 95% CI: 0.86-1.11; P = 0.72), major bleeding events (RR 0.96; 95% CI: 0.50-1.84; P = 0.91), and any bleeding events (RR: 1.09; 95% CI: 0.82-1.44; P = 0.56). CONCLUSION: Among patients who underwent knee or hip arthroplasty, aspirin prophylaxis was found to be associated with similar efficacy and safety outcomes when compared with anticoagulants. When compared with placebo, aspirin prophylaxis was associated with significantly reduced VTE and a comparable safety profile.

Aspirin for venous thromboembolism prophylaxis after hip or knee arthroplasty: An updated meta-analysis of randomized controlled trials.

BACKGROUND: Patients who undergo knee or hip arthroplasty are at a significant risk of venous thromboembolism (VTE) development (pulmonary embolism and/or deep-vein thrombosis). Many different thromboprophylactic strategies have been used for the prevention of VTE in these patients with different outcomes. Therefore, our aim was to evaluate the efficacy and safety of aspirin prophylaxis when compared with placebo or anticoagulants in this population of patients. METHODS: A comprehensive electronic database search was conducted for all randomized controlled trials (RCTs) comparing the clinical outcomes of aspirin versus placebo or anticoagulants for the prevention of VTE after knee or hip arthroplasty. The primary outcome was VTE incidence. Secondary outcomes included any bleeding, major bleeding and mortality. We calculated risk ratios (RRs) and 95% confidence intervals (CIs) using a random-effects model at the longest possible follow-up period. RESULTS: We included 13 RCTs with a total of 20,115 patients with a mean age of 67.15 ±â€¯9.54 and 24.39% males. Aspirin was found to be associated with a non-significantly reduced VTE events compared with other thromboprophylactic methods (RR 0.87; 95% CI: 0.61-1.23; P = 0.43). Compared with placebo, aspirin was associated with significant reduction of VTE (RR 0.65; 95% CI: 0.47-0.89; P = 0.008). There were no significant differences in the clinical outcomes between all groups with regard to mortality (RR 0.98; 95% CI: 0.86-1.11; P = 0.72), major bleeding events (RR 0.96; 95% CI: 0.50-1.84; P = 0.91), and any bleeding events (RR: 1.09; 95% CI: 0.82-1.44; P = 0.56). CONCLUSION: Among patients who underwent knee or hip arthroplasty, aspirin prophylaxis was found to be associated with similar efficacy and safety outcomes when compared with anticoagulants. When compared with placebo, aspirin prophylaxis was associated with significantly reduced VTE and a comparable safety profile.

De-Escalation of Antiplatelet Therapy in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Clinical Trials.

AIMS: Patients with acute coronary syndrome undergoing percutaneous coronary intervention (PCI) are recommended to be placed on potent P2Y12 blockade. However, the long-term bleeding risk is high. Therefore, despite no definitive evidence, switching to clopidogrel beyond the acute phase is common. We aimed to evaluate the clinical outcomes of antiplatelet de-escalation compared with continuation in patients treated with PCI. METHODS: We searched databases for randomized clinical trials (RCTs) that evaluated the safety and efficacy of antiplatelet de-escalation compared with continuation in patients treated with PCI. Pooled summary estimates were calculated. RESULTS: We included 3 RCTs with 3391 patients (median follow-up: 12 months). Compared with the continued group, the net clinical outcome (composite of bleeding or thrombotic events) was significantly reduced in the group switched to clopidogrel (8.7% vs 12.1%; risk ratio [RR]: 0.64; 95% confidence interval [CI]: 0.43-0.97; P = .03). However, there were similar clinical outcomes between groups for major adverse cardiovascular events (MACE; RR: 0.78; 95% CI: 0.55-1.11; P = .17), all Bleeding Academic Research Consortium (BARC) types bleeding (RR: 0.61; 95% CI: 0.33-1.11; P = .10), or BARC types ≥2 bleeding (RR: 0.49; 95% CI: 0.19-1.26; P = .14). CONCLUSIONS: Our results suggest a net clinical benefit of de-escalation therapy shortly after PCI, without increased risk of MACE. Larger randomized trials will be necessary to confirm these findings.

Haloperidol for the management of delirium in adult intensive care unit patients: A systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Delirium commonly presents as a complication in critically ill patients. Our aim is to perform a meta-analysis investigating the role of haloperidol versus placebo in management (treatment and prophylaxis), of delirium in intensive care unit (ICU). MATERIALS AND METHODS: Our study is a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing haloperidol versus placebo for treatment and/or prophylaxis of ICU-related delirium. RESULTS: Six RCTs representing 2552 patients. There was no significant difference between haloperidol and placebo-treated patients in short-term all-cause mortality (risk ratio [RR] 0.96; 95% confidence interval [CI] 0.81-1.14; P = 0.67), incidence of delirium (RR 0.93; 95% CI 0.65-1.34; P = 0.70), ICU length of stay (Mean difference [MD] 0.00 days; 95% CI -0.82-0.83; P = 0.99), or delirium/coma-free days (MD 0.09; 95% CI -0.05-0.24; P = 0.21). Haloperidol was not associated with increased risk for serious adverse events (RR 0.65; 95% CI 0.23-1.88; P = 0.43), QTc prolongation (RR 0.87; 95% CI 0.63-1.19; P = 0.38), or extrapyramidal symptoms (RR 0.84; 95% CI 0.57-1.23; P = 0.37). CONCLUSION: Among critically ill patients, haloperidol administration compared with placebo does not significantly affect short-term mortality, incidence of delirium, ICU length of stay, or delirium or coma-free days. Additionally, there was no increased risk of adverse events.

Comparison of Coronary Artery Bypass Grafting and Drug-Eluting Stents in Patients with Left Main Coronary Artery Disease and Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Treatment of left main coronary artery disease (LMCAD) in patients with chronic kidney disease (CKD) with either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) remains controversial. Therefore, we performed a meta-analysis to evaluate the optimal choice of therapy when treating LMCAD in patients with CKD. METHOD: We performed an electronic database search of Pubmed, Embase, and Cochrane Library for all studies that compared PCI with CABG when treating LMCAD in the setting of CKD. Major adverse cardiac and cerebrovascular events (MACCE) were the primary outcome. Secondary outcomes included myocardial infarction (MI), cerebrovascular events, all-cause mortality, and repeat revascularization. RESULTS: Our analysis included 5 studies (2 randomized controlled trial and 3 retrospective) representing a total of 1212 patients. Mean follow up was 3.4 ±â€¯1.3 years. Our study demonstrated a significant reduction in MACCE for patients treated with CABG compared with PCI (odd ratio [OR] 0.72; 95% confidence interval [CI] 0.55-0.95, P = 0.02, I2 = 0%). We also found a significant reduction in both MI (OR 0.55; 95% CI 0.34-0.87; P = 0.01; I2 = 0%) and repeat revascularization (OR 0.22; 95% CI 0.10-0.51; P < 0.001, I2 = 63%) in the CABG group. However, CABG was associated with increased risks of cerebrovascular disease events compared with PCI (OR 2.04; 95% CI 1.02-4.08; P = 0.04, I2 = 0%). CONCLUSION: In patients with CKD requiring LMCAD intervention, CABG is associated with a lower risk of MACCE, MI, and repeat revascularization, however it was associated with an increased risk of cerebrovascular accidents when compared to patients who received PCI therapy. Further RCTs with sufficient power are required to confirm these findings.

Triple versus dual inhaler therapy in moderate-to-severe COPD: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Treatment of chronic obstructive pulmonary disease (COPD) is evolving specially with triple inhaler therapy. OBJECTIVES: To perform a meta-analysis to ascertain the safety and efficacy of triple inhaler therapy consisting of an inhaled-glucocorticoid (ICS), long-acting muscarinic antagonist (LAMA) and long-acting beta2-agonist (LABA) when compared with dual therapy (ICS-LABA or LAMA-LABA). METHODS: We performed an electronic database search to include randomized controlled trials (RCTs) comparing between triple and dual inhalers. Pooled rate-ratio (RR) or odds-ratio (OR) for dichotomous data and weighted mean difference (MD) for continuous data were calculated with their corresponding 95% confidence interval (CI). RESULTS: Our study included 12 RCTs totaling 19,322 patients, mean age of 65 ± 8.2 years and 68.2% were male. Pooled analysis demonstrated a significant reduction in moderate-to-severe COPD exacerbations with triple therapy (RR 0.75; 95% CI 0.69-0.83; P < 0.01). Additionally, triple therapy caused significant increase in trough FEV1 (MD 0.09 L; 95% CI 0.07-0.12; P < 0.01), significant reduction in the mean St. George's Respiratory Questionnaire (SGRQ) score (MD -1.67; 95% CI -2.02- -1.31; P < 0.01), and more patients experienced ≥ 4 points reduction of SGRQ score (OR 1.27; 95% CI 1.19-1.35; P < 0.01). Triple therapy was associated with an increased risk of pneumonia when compared to LABA/LAMA (OR 1.25; 95% 1.03-1.97; P = 0.03) but there were no significant differences in other adverse events between triple and dual inhalers. CONCLUSIONS: Among patients with moderate-to-severe COPD, triple inhaler therapy was associated with a reduction of moderate-to-severe COPD exacerbations, improved lung function and improved quality of life when compared to dual inhaler therapy but with an increased pneumonia risk.

Safety and efficacy of aspirin for primary prevention of cancer: a meta-analysis of randomized controlled trials.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.