Plasma exchange for acute and acute-on-chronic liver failure: A systematic review and meta-analysis.

Plasma exchange (PE) is a promising therapeutic option in patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). However, the impact of PE on patient survival in these syndromes is unclear. We aimed to systematically investigate the use of PE in patients with ALF and ACLF compared with standard medical therapy (SMT). We searched PubMed/Embase/Cochrane databases to include all studies comparing PE versus SMT for patients ≥ 18 years of age with ALF and ACLF. Pooled risk ratios (RR) with corresponding 95% CIs were calculated by the Mantel-Haenszel method within a random-effect model. The primary outcome was 30-day survival for ACLF and ALF. Secondary outcomes were overall and 90-day survival for ALF and ACLF, respectively. Five studies, including 343 ALF patients (n = 174 PE vs. n = 169 SMT), and 20 studies, including 5,705 ACLF patients (n = 2,856 PE vs. n = 2,849 SMT), were analyzed. Compared with SMT, PE was significantly associated with higher 30-day (RR 1.41, 95% CI 1.06-1.87, p = 0.02) and overall (RR 1.35, 95% CI 1.12-1.63, p = 0.002) survival in ALF patients. In ACLF, PE was also significantly associated with higher 30-day (RR 1.36, 95% CI 1.22-1.52, p < 0.001) and 90-day (RR 1.21, 95% CI 1.10-1.34, p < 0.001) survival. On subgroup analysis of randomized controlled trials, results remained unchanged in ALF, but no differences in survival were found between PE and SMT in ACLF. In conclusion, PE is associated with improved survival in ALF and could improve survival in ACLF. PE may be considered in managing ALF and ACLF patients who are not liver transplant (LT) candidates or as a bridge to LT in otherwise eligible patients. Further randomized controlled trials are needed to confirm the survival benefit of PE in ACLF.

Cognitive behavioral therapy for depression in patients with heart failure: a systematic review and metanalysis of randomized control trials.

Major depression (MD) is prevalent in patients with heart failure (HF) and contributes to increased risk of hospitalization and mortality. The implementation of cognitive behavioral therapy (CBT) has become a key strategy for treating HF patients' depression. We performed a comprehensive literature search for studies that evaluated the efficacy of adjunctive CBT compared to the standard of care (SOC) in HF patients with MD. The primary outcome was the depression scale (post-intervention and by the end of follow-up). The secondary outcomes were the quality of life (QoL), self-care scores, and 6-min walk test distance(6-MW). The standardized mean difference (SMD) and corresponding 95% confidence intervals (CIs) were calculated using the random-effects model. A total of 6 RCTs with 489 patients (244 in the CBT group and 245 in the SOC group) were included. As compared to the SOC, CBT was associated with a statistically significant improvement in the post-interventional depression scale (SMD: -0.45, 95%CI: -0.69, -0.21; P < 0.01) and by the end of follow-up (SMD: -0.68, 95%CI: -0.87, -0.49; P < 0.01). Furthermore, CBT significantly improved the QoL (SMD: -0.45, 95%CI: -0.65, -0.24; P < 0.01). However, there were no differences in the self-care scores (SMD: 0.17, 95%CI: -0.08, 0.42; P = 0.18) or in 6-MW (SMD: 0.45, 95%CI: -0.39, 1.28; P = 0.29) between the two groups. According to our meta-analysis of published clinical studies, CBT may be more effective than standard therapy at enhancing depression scores and quality of life. To assess the long-term clinical effects of CBT in heart failure patients, larger and more powerful RCTs are required.

Endoscopic Versus Conservative Therapy for Bleeding Peptic Ulcer with Adherent Clot: A Comprehensive Systematic Review and Meta-Analysis.

INTRODUCTION: Peptic ulcers with adherent clots are associated with a high-risk of rebleeding and mortality. However, the optimal management of bleeding ulcers with adherent clots remains unclear. We conducted this systematic review and meta-analysis to compare endoscopic therapy and conservative therapy to manage bleeding ulcers with adherent clots. METHODS: We systematically searched PubMed, Embase, and Web of Science databases through October 2022 to include all studies comparing the endoscopic and conservative therapeutic approaches for bleeding ulcers with adherent clots. Our primary outcome was rebleeding (overall and 30-day). The secondary outcomes were mortality (overall and 30-day), need for surgery, and length of hospital stay (LOS). The random-effects model was used to calculate the pooled odds ratios (OR) and mean differences (MD) with the corresponding confidence intervals (CI) for proportional and continuous variables, respectively. RESULTS: Eleven studies (9 RCTs) with 833 patients (431 received endoscopic therapy vs. 402 received conservative therapy) were included. Overall, endoscopic therapy was associated with lower overall rebleeding (OR 0.41, 95% CI 0.22-0.79, P = 0.007), 30-day rebleeding (OR 0.43, 95% CI 0.21-0.89, P = 0.002), overall mortality (OR 0.47, 95% CI 0.23-0.95, P = 0.04), 30-day mortality (OR 0.43, 95% CI 0.21-0.89, P = 0.002), need for surgery (OR 0.44, 95% CI 0.21-0.95, P = 0.04), and LOS (MD - 3.17 days, 95% CI - 4.14, - 2.19, P < 0.00001). However, subgroup analysis of randomized controlled trials (RCTs) showed no significant difference in overall mortality (OR 0.78, 95% CI 0.24-2.52, P = 0.68) between the two strategies, with numerically lower but statistically non-significant rates of overall rebleeding (7.2% vs. 18.5%, respectively; OR 0.42, 95% CI 0.17-1.05, P = 0.06), statistically lower rate of need for surgery (OR 0.28, 95% CI 0.08-0.96, P = 0.04) with endoscopic therapy compared to conservative therapy. CONCLUSIONS: Our meta-analysis demonstrates that endoscopic therapy was overall associated with lower rates of rebleeding (overall and 30-day), mortality (overall and 30-day), need for surgery, and LOS, compared to conservative therapy for the management of bleeding ulcers with adherent clots. However, subgroup analysis of RCTs showed that endoscopic therapy was associated with numerically lower but statistically non-significant rates of overall rebleeding and a statistically lower rate of need for surgery compared to conservative therapy with similar overall mortality rates. Combined treatment with thermal therapy and injection therapy was the most effective treatment modality in reducing rebleeding risk. Further large-scale RCTs are needed to validate our findings.

Pulse versus nonpulse steroid regimens in patients with coronavirus disease 2019: A systematic review and meta-analysis.

Systemic steroids are associated with reduced mortality in hypoxic patients with coronavirus disease 2019 (COVID-19). However, there is no consensus on the doses of steroid therapy in these patients. Several studies showed that pulse dose steroids (PDS) could reduce the progression of COVID-19 pneumonia. However, data regarding the role of PDS in COVID-19 is still unclear. Therefore, we performed this meta-analysis to evaluate the role of PDS in COVID-19 patients compared to nonpulse steroids (NPDS). Comprehensive literature search of PubMed, Embase, Cochrane Library, and Web of Science databases from inception through February 10, 2022 was performed for all published studies comparing PDS to NPDS therapy to manage hypoxic patients with COVID-19. Primary outcome was mortality. Secondary outcomes were the need for endotracheal intubation, hospital length of stay (LOS), and adverse events in the form of superimposed infections. A total of 10 observational studies involving 3065 patients (1289 patients received PDS and 1776 received NPDS) were included. The mortality rate was similar between PDS and NPDS groups (risk ratio [RR]: 1.23, 95% confidence interval [CI]: 0.92-1.65, p = 0.16). There were no differences in the need for endotracheal intubation (RR: 0.71, 95%: CI 0.37-1.137, p = 0.31), LOS (mean difference: 1.93 days; 95% CI: -1.46-5.33; p = 0.26), or adverse events (RR: 0.93, 95% CI: 0.56-1.57, p = 0.80) between the two groups. Compared to NPDS, PDS was associated with similar mortality rates, need for endotracheal intubation, LOS, and adverse events. Given the observational nature of the included studies, randomized controlled trials are warranted to validate our findings.

Lung ultrasound-guided management to reduce hospitalization in chronic heart failure: a systematic review and meta-analysis.

Pulmonary edema is a leading cause of hospital admissions, morbidity, and mortality in heart failure (HF) patients. A point-of-care lung ultrasound (LUS) is a useful tool to detect subclinical pulmonary edema. We performed a comprehensive literature search of multiple databases for studies that evaluated the clinical utility of LUS-guided management versus standard care for HF patients in the outpatient setting. The primary outcome of interest was HF hospitalization. The secondary outcomes were all-cause mortality, urgent visits for HF worsening, acute kidney injury (AKI), and hypokalemia rates. Pooled risk ratio (RR) and corresponding 95% confidence intervals (CIs) were calculated and combined using random-effect model meta-analysis. A total of 3 randomized controlled trials including 493 HF patients managed in the outpatient setting (251 managed with LUS plus physical examination (PE)-guided therapy vs. 242 managed with PE-guided therapy alone) were included in the final analysis. The mean follow-up period was 5 months. There was no significant difference in HF hospitalization rate between the two groups (RR 0.65; 95% CI 0.34-1.22; P = 0.18). Similarly, there was no significant difference in all-cause mortality (RR 1.39; 95% CI 0.68-2.82; P = 0.37), AKI (RR 1.27; 95% CI 0.60-2.69; P = 0.52), and hypokalemia (RR 0.72; 95% CI 0.21-2.44; P = 0.59). However, LUS-guided therapy was associated with a lower rate for urgent care visits (RR 0.32; 95% CI 0.18-0.59; P = 0.0002). Our study demonstrated that outpatient LUS-guided diuretic therapy of pulmonary congestion reduces urgent visits for worsening symptoms of HF. Further studies are needed to evaluate LUS utility in the outpatient treatment of HF.

Efficacy of remote physiological monitoring-guided care for chronic heart failure: an updated meta-analysis.

Previous studies have reported contradictory findings on the utility of remote physiological monitoring (RPM)-guided management of patients with chronic heart failure (HF). Multiple databases were searched for studies that evaluated the clinical efficacy of RPM-guided management versus standard of care (SOC) for HF patients. The primary outcome was HF-related hospitalization (HFH). The secondary outcomes were all-cause mortality, cardiovascular-related (CV) mortality, and emergency department (ED) visits. Pooled relative risk (RR) and corresponding 95% confidence intervals (CIs) were calculated and combined using a random-effects model. A total of 16 randomized controlled trials, including 8679 HF patients (4574 managed with RPM-guided therapy vs. 4105 managed with SOC), were included in the final analysis. The average follow-up period was 15.2 months. There was no significant difference in HFH rate between the two groups (RR: 0.94; 95% CI: 0.84-1.07; P = 0.36). Similarly, there were no significant differences in CV mortality (RR 0.86, 95% CI 0.73-1.02, P = 0.08) or in ED visits (RR 0.80, 95% CI 0.59-1.08, P = 0.14). However, RPM-guided therapy was associated with a borderline statistically significant reduction in all-cause mortality (RR: 0.88; 95% CI: 0.78-1.00; P = 0.05). Subgroup analysis based on the strategy of RPM showed that both hemodynamic and arrhythmia telemonitoring-guided management can reduce the risk of HFH (RR: 0.79; 95% CI: 0.64-0.97; P = 0.02) and (RR: 0.79; 95% CI: 0.67-0.94; P = 0.008) respectively. Our study demonstrated that RPM-guided diuretic therapy of HF patients did not reduce the risk of HFH but can improve survival. Hemodynamic and arrhythmia telemonitoring-guided management could reduce the risk of HF-related hospitalizations.

Fluvoxamine in Nonhospitalized Patients With Acute COVID-19 Infection and the Lack of Efficacy in Reducing Rates of Hospitalization, Mechanical Ventilation, and Mortality in Placebo-Controlled Trials: A Systematic Review and Meta-Analysis.

BACKGROUND: Recent clinical trials have investigated the use of fluvoxamine in preventing clinical deterioration in nonhospitalized patients with acute COVID-19 infection via stimulation of sigma-1 receptors, which regulates cytokine production and functional inhibition of acid sphingomyelinase activity, which may prevent infection of epithelial cells with SARS-CoV-2. However, the role of fluvoxamine is currently unclear because of a paucity of studies, particularly because the drug is being repurposed as an immunomodulatory and antiviral agent. STUDY QUESTION: Aim of our meta-analysis was to investigate the efficacy of fluvoxamine in nonhospitalized patients with acute COVID-19 infection. DATA SOURCE: Comprehensive literature search of PubMed, Embase, Cochrane Library databases, and Web of Science was performed from inception to February 10, 2022, for studies comparing fluvoxamine versus placebo for outpatient management of COVID-19. STUDY DESIGN: The primary outcome of interest was rate of hospitalization. The secondary outcomes were rates of patients requiring mechanical ventilation and mortality. The random-effects model was used to calculate the risk ratios (RR) and confidence intervals (CI). A P value <0.05 was considered statistically significant. Heterogeneity was assessed using the Higgins I2 index. RESULTS: Three studies (2 randomized controlled trials and one prospective cohort trial) involving 1762 patients were included in the meta-analysis. In patients who received fluvoxamine compared with placebo, there was no significant difference in rates of hospitalization (RR 0.26, 95% CI, 0.04-1.73, P = 0.16, I2 = 62%), mechanical ventilation (RR 0.73, 95% CI, 0.45-1.19, P = 0.21, I2 = 0%), and mortality (RR 0.67, 95% CI, 0.37-1.22, P = 0.19, I2 = 0%). CONCLUSION: Current evidence does not indicate a significant effect of fluvoxamine on the rates of hospitalization, mechanical ventilation, and mortality of patients with COVID-19 infection.

Inhaled Pulmonary Vasodilators in COVID-19 Infection: A Systematic Review and Meta-Analysis.

Introduction: Inhaled pulmonary vasodilators (IPVD) have been previously studied in patients with non-coronavirus disease-19 (COVID-19) related acute respiratory distress syndrome (ARDS). The use of IPVD has been shown to improve the partial pressure of oxygen in arterial blood (PaO2), reduce fraction of inspired oxygen (FiO2) requirements, and ultimately increase PaO2/FiO2 (P/F) ratios in ARDS patients. However, the role of IPVD in COVID-19 ARDS is still unclear. Therefore, we performed this meta-analysis to evaluate the role of IPVD in COVID-19 patients. Methods: Comprehensive literature search of PubMed, Embase, Web of Science and Cochrane Library databases from inception through April 22, 2022 was performed for all published studies that utilized IPVD in COVID-19 ARDS patients. The single arm studies and case series were combined for a 1-arm meta-analysis, and the 2-arm studies were combined for a 2-arm meta-analysis. Primary outcomes for the 1-arm and 2-arm meta-analyzes were change in pre- and post-IPVD P/F ratios and mortality, respectively. Secondary outcomes for the 1-arm meta-analysis were change in pre- and post-IPVD positive end-expiratory pressure (PEEP) and lung compliance, and for the 2-arm meta-analysis the secondary outcomes were need for endotracheal intubation and hospital length of stay (LOS). Results: 13 single arm retrospective studies and 5 case series involving 613 patients were included in the 1-arm meta-analysis. 3 studies involving 640 patients were included in the 2-arm meta-analysis. The pre-IPVD P/F ratios were significantly lower compared to post-IPVD, but there was no significant difference between pre- and post-IPVD PEEP and lung compliance. The mortality rates, need for endotracheal intubation, and hospital LOS were similar between the IPVD and standard therapy groups. Conclusion: Although IPVD may improve oxygenation, our investigation showed no benefits in terms of mortality compared to standard therapy alone. However, randomized controlled trials are warranted to validate our findings.

Efficacy of ICD/CRT-D Remote Monitoring in Patients With HFrEF: a Bayesian Meta-analysis of Randomized Controlled Trials.

PURPOSE OF REVIEW: To evaluate remote monitoring using implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy defibrillator (CRT-D) devices as an adjunctive tool to the traditional care of patients with heart failure (HF). RECENT FINDINGS: We included 11 trials encompassing 5965 patients. Absolute risk difference (ARD) with 95% credible interval (CrI) was estimated. Pooled (posterior) risk difference was computed using Bayesian hierarchical methods. The ARD for mortality was centered at - 0.01 (95% CrI: - 0.03; 0.01, Tau: 0.02), with an 82% probability of ARD of ICD/CRT-D remote monitoring with respect to control being less than 0. The ARD for cardiovascular mortality was centered at - 0.03 (95% CrI: - 0.11; 0.05, Tau: 0.10), with an 84% probability of ARD of ICD/CRT-D remote monitoring with respect to control being less than 0. ICD/CRT-D remote monitoring in patients with HF is associated with a higher probability of reduced all-cause and cardiovascular mortality compared with standard care alone.

Efficacy and Safety of Direct Oral Anticoagulants Versus Vitamin K Antagonists in the Treatment of Left Ventricular Thrombus: A Systematic Review and Meta-analysis.

BACKGROUND: Left ventricular thrombus (LVT) may develop in systolic heart failure or after acute myocardial infarction. The current recommendations support the use of vitamin K antagonists (VKAs) for the treatment of LVT. Limited data exist regarding the use of direct oral anticoagulants (DOACs) in patients with LVT. This meta-analysis aims to investigate the efficacy and safety of DOACs versus VKAs for LVT. METHODS: We performed a comprehensive literature search using PubMed, Embase, and Cochrane Library databases through November 2020 for all studies that evaluated the efficacy and safety of DOACs versus VKAs in patients with LVT. The primary outcomes were LVT resolution, overall thromboembolic events, and thromboembolic stroke. The secondary outcomes were major bleeding and all-cause mortality. Pooled risk ratio (RR) and 95% confidence intervals (CIs) were obtained by the Mantel-Haenszel method within a random-effects model. Heterogeneity was assessed by I2 statistic. RESULTS: A total of 11 studies including 2153 patients with LVT on anticoagulation (570 on DOACs vs. 1583 on VKAs) were included. LVT resolution was significantly higher in DOACs compared with VKAs [RR: 1.18 (95% CI: 1.04-1.35); P = 0.01, I2 = 25%]. However, no significant difference existed between DOACs and VKAs regarding overall thromboembolic events [RR: 1.10 (95% CI: 0.75-1.62); P = 0.61, I2 = 0%] and thromboembolic stroke [RR: 0.63 (95% CI: 0.39-1.02); P = 0.06, I2 = 0%]. Major bleeding [RR: 1.00 (95% CI: 0.66-1.51); P = 0.99, I2 = 4%] and all-cause mortality [RR: 0.84 (95% CI: 0.50-1.43); P = 0.53, I2 = 0%] were similar between the 2 groups. CONCLUSIONS: DOACs seem to be more efficacious in achieving LVT resolution compared with VKAs. However, there was no significant difference between the 2 groups in thromboembolic events, major bleeding, and all-cause mortality. Randomized controlled trials are needed to confirm our findings.

Direct Oral Anticoagulants Versus Warfarin in Morbidly Obese Patients With Nonvalvular Atrial Fibrillation: A Systematic Review and Meta-analysis.

BACKGROUND: Direct oral anticoagulants (DOACs) have been increasingly preferred over warfarin; however, The International Society of Thrombosis and Hemostasis recommended avoiding the use of DOACs in morbidly obese patients (body mass index >40 or weight >120 kg) because of limited clinical data. STUDY QUESTION: Are DOACs effective and safe in morbidly obese patients with nonvalvular atrial fibrillation (NVAF). DATA SOURCES: We performed a comprehensive search for published studies indexed in PubMed/MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials that evaluated the efficacy and safety of DOACs in morbidly obese patients with NVAF. STUDY DESIGN: Information on patient characteristics, comorbidities, primary anticoagulation indications, pharmacologic treatment, and outcomes were collected. The primary outcome of interest was stroke or systemic embolism (SSE) rate. The secondary outcome was major bleeding (MB). RESULTS: A total of 10 studies including, 89,494 morbidly obese patients with NVAF on oral anticoagulation therapy (45,427 on DOACs vs. 44,067 on warfarin) were included in the final analysis. The SSE rate was significantly lower in DOACs group compared with warfarin group [odds ratio: 0.71; 95% confidence interval (CI): 0.62-0.81; P < 0.0001; I2 = 0%]. MB rate was also significantly lower in DOACs group compared with the warfarin group (odds ratio: 0.60; 95% CI: 0.46-0.78; P < 0.0001; I2 = 86%). On subgroup analysis, SSE and MB event rates were significantly lower in rivaroxaban and apixaban than warfarin; however, dabigatran showed noninferiority to warfarin in SSE rate but superiority in the safety outcome. CONCLUSIONS: Our meta-analysis demonstrated that DOACs are effective and safe with statistical superiority when compared with warfarin in morbidly obese patients. Large-scale randomized clinical trials are needed to further evaluate the efficacy and safety of DOACs in this cohort of patients.