Chronic Anticoagulation in Patients with Atrial Fibrillation and COVID-19: A Systematic Review and Meta-Analysis. / Anticoagulação Crônica em Pacientes com Fibrilação Atrial e COVID-19: Uma Revisão Sistemática e Metanálise.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with hypercoagulability. It remains uncertain whether ongoing anticoagulation for atrial fibrillation (AF) in patients who later contract COVID-19 improves clinical outcomes. OBJECTIVES: To compare chronic oral anticoagulation with no previous anticoagulation in patients with AF who contracted a COVID-19 infection concerning the outcomes of all-cause mortality, COVID-19 mortality, intensive care unit (ICU) admission, and hospitalization. METHODS: We systematically searched PubMed, Embase, and Cochrane Library for eligible studies from inception to December 2022. We included studies comparing COVID-19 outcomes in patients with versus without prior chronic anticoagulation for AF. Risk ratios (RR) with 95% confidence intervals (CI) were pooled with a random-effects model. The level of significance was set at p < 0.05. Quality assessment and risk of bias were performed according to Cochrane recommendations. RESULTS: Ten studies comprising 1,177,858 patients with COVID-19 and AF were identified, of whom 893,772 (75.9%) were on prior chronic anticoagulation for AF. In patients with COVID-19, being on chronic anticoagulation for AF significantly reduced all-cause mortality (RR 0.75; 95% CI 0.57 to 0.99; p = 0.048; I2 = 89%) and COVID-19-related mortality (RR 0.76; 95% CI 0.72 to 0.79; p < 0.001; I2 = 0%) when compared with no prior anticoagulation. In contrast, there was no difference between groups regarding hospitalization (RR 1.08; 95% CI 0.82 to 1.41; p = 0.587; I2 = 95%) or ICU admission (RR 0.86; 95% CI 0.68 to 1.09; p = 0.216; I2 = 69%). CONCLUSIONS: In this meta-analysis, chronic anticoagulation for patients with AF who contracted COVID-19 was associated with significantly lower rates of all-cause mortality and COVID-19-related mortality as compared with no previous anticoagulation.

FUNDAMENTO: A doença por coronavírus 2019 (COVID-19) está associada à hipercoagulabilidade. Permanece incerto se a anticoagulação contínua para fibrilação atrial (FA) em pacientes que posteriormente contraem COVID-19 melhora os desfechos clínicos. OBJETIVOS: Comparar a anticoagulação oral crônica com ausência de anticoagulação prévia em pacientes com FA que contraíram uma infecção por COVID-19 em relação aos desfechos de mortalidade por todas as causas, mortalidade por COVID-19, admissão em unidade de terapia intensiva (UTI) e hospitalização. MÉTODOS: Buscamos sistematicamente no PubMed, Embase e Cochrane Library estudos elegíveis desde o início até dezembro de 2022. Incluímos estudos que compararam desfechos de COVID-19 em pacientes com e sem anticoagulação crônica prévia para FA. Foram agrupadas razões de risco (RR) com intervalos de confiança (IC) de 95% por meio de um modelo de efeitos aleatórios. O nível de significância foi estabelecido em p < 0,05. As avaliações da qualidade e do risco de viés foram realizadas de acordo com as recomendações da Cochrane. RESULTADOS: Foram identificados 10 estudos abrangendo 1.177.858 pacientes com COVID-19 e FA, dos quais 893.772 (75,9%) estavam em anticoagulação crônica prévia para FA. Em pacientes com COVID-19, a anticoagulação crônica para FA reduziu significativamente a mortalidade por todas as causas (RR 0,75; IC 95% 0,57 a 0,99; p = 0,048; I2 = 89%) e a mortalidade relacionada à COVID-19 (RR 0,76; IC 95% 0,72 a 0,79; p < 0,001; I2 = 0%) quando comparada com a ausência de anticoagulação prévia. Em contrapartida, não houve diferença entre os grupos em relação à hospitalização (RR 1,08; IC 95% 0,82 a 1,41; p = 0,587; I2 = 95%) ou internação em UTI (RR 0,86; IC 95% 0,68 a 1,09; p = 0,216; I2 = 69%). CONCLUSÕES: Nesta metanálise, a anticoagulação crônica para pacientes com FA que contraíram COVID-19 foi associada a taxas significativamente mais baixas de mortalidade por todas as causas e mortalidade relacionada à COVID-19 em comparação com a ausência de anticoagulação anterior.

Laparoscopic Versus Open Gastrectomy for Advanced Gastric Cancer: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Laparoscopy-assisted gastrectomy (LAG) is a well-established surgical technique in treating patients with early gastric cancer. However, the efficacy and safety of LAG versus open gastrectomy (OG) in patients with advanced gastric cancer (AGC) remains unclear. METHODS: We systematically searched PubMed, Embase, and Cochrane Library in June 2023 for RCTs comparing LAG versus OG in patients with AGC. We pooled risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) for binary and continuous endpoints, respectively. We performed all statistical analyses using R software version 4.3.1 and a random-effects model. RESULTS: Nine RCTs comprising 3827 patients were included. There were no differences in terms of intraoperative complications (RR 1.14; 95% CI 0.72 to 1.82), number of retrieved lymph nodes (MD -0.54 lymph nodes; 95% CI -1.18 to 0.09), or mortality (RR 0.91; 95% CI 0.30 to 2.83). LAG was associated with a longer operative time (MD 49.28 minutes; 95% CI 30.88 to 67.69), lower intraoperative blood loss (MD -51.24 milliliters; 95% CI -81.41 to -21.06), shorter length of stay (MD -0.83 days; 95% CI -1.60 to -0.06), and higher incidence of pancreatic fistula (RR 2.44; 95% CI 1.08 to 5.50). Postoperatively, LAG was also superior to OG in reducing bleeding rates (RR 0.44; 95% CI 0.22 to 0.86) and time to first flatus (MD -0.27 days; 95% CI -0.47 to -0.07), with comparable results in anastomotic leakage, wound healing issues, major complications, time to ambulation, or time to first liquid intake. In the long-term analyses at 3 and 5 years, there were no significant differences between LAG and OG in terms of overall survival (RR 0.99; 95% CI 0.96 to 1.03) or relapse-free survival (RR 0.99; 95% CI 0.94 to 1.04). CONCLUSION: This meta-analysis of RCTs suggests that LAG may be an effective and safe alternative to OG for treating AGC; albeit, it may be associated with an increased risk for pancreatic fistula.

Comparative efficacy of carfilzomib, lenalidomide, and dexamethasone (KRd) versus bortezomib, lenalidomide, and dexamethasone (VRd) in newly-diagnosed multiple myeloma: A systematic review and meta-analysis.

In view of the increasing data evaluating carfilzomib-based induction for newly-diagnosed multiple myeloma (NDMM), we conducted a systematic review and meta-analysis comparing the efficacy of carfilzomib/lenalidomide/dexamethasone (KRd) versus bortezomib/lenalidomide/dexamethasone (VRd). Three studies totaling 1597 patients (50% KRd-treated, 50% VRd-treated) were included. Despite similar survival outcomes and overall response rate compared with the VRd arm, KRd-treated subjects showed higher odds of achieving complete responses and measurable residual disease negativity. Among patients with high-risk cytogenetics (n = 348), KRd was associated with significant improvement in progression-free survival (HR = 0.70; 95% CI = 0.50-0.97; p = .03; I2 = 0%), suggesting carfilzomib-based induction may be preferable in this NDMM subpopulation.

Cardio-protective effects of statins in patients undergoing anthracycline-based chemotherapy: An updated meta-analysis of randomized controlled trials.

INTRODUCTION: Several interventions have been tested for cardio-protection against anthracycline-induced cancer therapy-related cardiovascular dysfunction (CTRCD). The role of statins in this setting remains unclear. METHODS: We systematically searched PubMed, Embase, Cochrane Library, Clinicaltrials.gov, and Web of Science for randomized controlled trials (RCTs) comparing statins versus control (placebo or no intervention) for preventing anthracycline-induced CTRCD. We applied a random-effects model to pool risk ratios (RR) and mean differences (MD) with 95 % confidence intervals (CI). RESULTS: We included seven RCTs comprising 887 patients with planned chemotherapy with anthracycline-based regimens, of whom 49.8 % were randomized to statins. Relative to placebo, statins significantly reduced the incidence of cardiotoxicity/CTRCD (RR 0.46; 95 % CI 0.29 to 0.72; p < 0.001). The left ventricular end-systolic volume was also lower in patients treated with statin (MD -3.12 mL; 95 % CI -6.13 to -0.12 mL; p = 0.042). There was no significant difference between groups in post-anthracycline left ventricular ejection fraction (LVEF) overall. CONCLUSION: In this meta-analysis of RCTs, statins were significantly associated with a lower incidence of anthracycline-induced CTRCD and attenuated changes in the left ventricular end-systolic volume. Thus, our findings suggest that statins should be considered as a cardio-protection strategy for patients with planned anthracycline-based chemotherapy.

Thromboembolic risk of carfilzomib or bortezomib in combination with lenalidomide and dexamethasone for newly diagnosed multiple myeloma: A comparative systematic review and meta-analysis.

Thrombosis represents a frequent and potentially severe complication in individuals diagnosed with multiple myeloma (MM). These events can be driven by both the disease as well as the therapies themselves. Overall, available evidence is inconclusive about the differential thrombogenicity of carfilzomib/lenalidomide/dexamethasone (KRd) and bortezomib/lenalidomide/dexamethasone (VRd). This meta-analysis compares the risk for venous thromboembolism (VTE; including deep venous thrombosis and pulmonary embolism) and arterial thromboembolism (ATE; including myocardial infarction and ischemic stroke) with KRd versus VRd as primary therapy for newly diagnosed MM (NDMM). Out of 510 studies identified after deduplication, one randomized controlled trial and five retrospective cohort studies were included. We analyzed 2304 patients (VRd: 1380; KRd: 924) for VTE events and 2179 patients (VRd: 1316; KRd: 863) for ATE events. Lower rates of VTE were observed in the VRd group when compared with the KRd group (6.16% vs. 8.87%; odds ratio [OR], 0.53; 95% confidence interval [CI], 0.32-0.88; p = .01). Both treatment groups exhibited minimal ATE incidence, with no significant difference between them (0.91% vs. 1.16%; OR, 1.01; 95% CI, 0.24-4.20; p = .99). In view of potential biases from retrospective studies, heterogeneity of baseline population characteristics, and limited access to patient-level data (e.g., VTE risk stratification and type of thromboprophylaxis regimen used) inherent to this meta-analysis, additional research is warranted to further validate our findings and refine strategies for thrombosis prevention in MM.

Incidence of mental health conditions following pediatric hospital admissions: analysis of a national database.

Introduction: Despite increasing survival of children following hospitalization, hospitalization may increase iatrogenic risk for mental health (MH) disorders, including acute stress, post-traumatic stress, anxiety, or depression. Using a population-based retrospective cohort study, we assessed the rates of new MH diagnoses during the 12 months after hospitalization, including the moderating effects of ICU exposure. Study design/methods: This was a retrospective case control study using the Truven Health Analytics insurance database. Inclusion criteria included children aged 3-21 years, insurance enrollment for >12 months before and after hospital admission. We excluded children with hospitalization 2 years prior to index hospitalization and those with prior MH diagnoses. We extracted admission type, ICD-10 codes, demographic, clinical, and service coordination variables from the database. We established age- and sex-matched cohorts of non-hospitalized children. The primary outcome was a new MH diagnosis. Multivariable regression methods examined the risk of incident MH disorder(s) between hospitalized and non-hospitalized children. Among hospitalized children, we further assessed effect modification from ICU (vs. non-ICU) stay, admission year, length of stay, medical complexity, and geographic region. Results: New MH diagnoses occurred among 19,418 (7%) hospitalized children, 3,336 (8%) ICU-hospitalized children and 28,209 (5%) matched healthy controls. The most common MH diagnoses were anxiety (2.5%), depression (1.9%), and stress/trauma (2.2%) disorders. Hospitalization increased the odds of new MH diagnoses by 12.3% (OR: 1.123, 95% CI: 1.079-1.17) and ICU-hospitalization increased these odds by 63% (OR: 1.63, 95% CI: 1.483-1.79) as compared to matched, non-hospitalized children. Children with non-complex chronic diseases (OR: 2.91, 95% CI: 2.84-2.977) and complex chronic diseases (OR: 5.16, 95% CI: 5.032-5.289) had a substantially higher risk for new MH diagnoses after hospitalization compared to patients with acute illnesses. Conclusion: Pediatric hospitalization is associated with higher, long-term risk of new mental health diagnoses, and ICU hospitalization further increases that risk within 12 months of the acute episode. Acute care hospitalization confers iatrogenic risks that warrant long-term mental and behavioral health follow-up.

Long-term impact of home-based monitoring after an admission for acute decompensated heart failure: a systematic review and meta-analysis of randomised controlled trials.

Background: Patients with heart failure have high rehospitalisation rates and poor cardiovascular outcomes. Home-based monitoring (HBM) has emerged with promising results in different settings. However, its long-term effects on patients recently admitted for acute decompensated heart failure (ADHF) remain uncertain. Methods: We systematically searched PubMed, Embase, and Cochrane Library for randomised controlled trials (RCTs) comparing HBM with usual care (UC) that were published between database inception and June 24, 2023. We included studies with patients admitted for ADHF in the previous 6 months and with a minimum follow-up of 6 months. We excluded studies with patients hospitalised for reasons other than ADHF and studies with disproportional education interventions between arms. Statistical analyses were performed using R software version 4.3.2. We pooled risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) for categorical and continuous outcomes, respectively. Cochrane Collaboration's tool for assessing risk of bias in RCTs (RoB 2) was used to assess study quality. Publication bias was assessed via funnel plots and Egger's test, and heterogeneity was assessed through I2 statistics and sensitivity analysis. The protocol for this systematic review and meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO, CRD42023465359). Findings: We included 16 RCTs comprising 4629 patients, of whom 2393 (51.7%) were randomised to HBM and 3150 (68%) were men. Follow-up ranged from six to fifteen months. As compared with UC, HBM significantly reduced all-cause mortality (RR 0.75; 95% CI 0.61, 0.91; p = 0.005), all-cause hospitalisations (RR 0.82; 95% CI 0.70, 0.97; p = 0.018), cardiovascular (CV) mortality (RR 0.53; 95% CI 0.36, 0.79; p = 0.002), hospitalisations for heart failure (RR 0.75; 95% CI 0.62, 0.91; p = 0.004), and CV hospitalisations (RR 0.72; 95% CI 0.55, 0.95; p = 0.018). There were no significant differences in length of hospital stay (MD 0.97 days; 95% CI -0.90, 2.84; p = 0.308). Interpretation: In patients recently admitted with ADHF, HBM significantly reduces long-term all-cause mortality and hospitalisations, CV mortality and hospitalisations, and hospitalisations for heart failure, as compared with UC. This supports the implementation of HBM as a standard practice to optimise patient outcomes following admissions for ADHF. However, future studies are warranted to evaluate the efficacy and safety of implementing HBM in the real-world setting. Funding: None.

Safety and efficacy of catheter ablation for atrial fibrillation in cancer survivors: a systematic review and meta-analysis

BACKGROUND: Cancer survivors are at increased risk for atrial fibrillation (AF). However, data on the efficacy and safety of catheter ablation (CA) in this population remain limited. Therefore, we aimed to perform a systematic review and meta-analysis comparing outcomes after CA for AF in patients with versus without prior or active cancer. METHODS: We systematically searched PubMed, Cochrane Library, and Embase from inception to April 2023 for studies comparing the safety and efficacy of CA for AF in cancer survivors. Outcomes of interest were bleeding events, late AF recurrence, and need for repeat ablation. Statistical analyses were performed using Review Manager 5.4.1. We pooled odds ratios (OR) with 95% confidence intervals (CI) for binary endpoints. RESULTS: We included 5 retrospective cohort studies comprising 998 patients, of whom 41.4% had a history of cancer. Cancer survivors were at significantly higher risk of clinically relevant bleeding (OR 2.17; 95% CI 1.17-4.0; p=0.01) as compared with those without cancer. The efficacy of CA for AF was similar between groups. Late AF recurrence at 12 months was not significantly different between patients with vs. without a history of cancer (OR 1.29; 95% CI 0.78-2.13; p=0.32). Similar findings were observed in the outcome of repeat ablations (OR 0.71; 95% CI 0.37-1.37; p=0.31). CONCLUSIONS: These findings suggest that cancer survivors have an increased risk of bleeding after CA for AF relative to patients without cancer, with no significant difference in the efficacy of CA for maintenance of sinus rhythm between groups. STUDY REGISTRATION: This systematic review is registered in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42023394538.

Safety and efficacy of catheter ablation for atrial fibrillation in cancer survivors: a systematic review and meta-analysis.

BACKGROUND: Cancer survivors are at increased risk for atrial fibrillation (AF). However, data on the efficacy and safety of catheter ablation (CA) in this population remain limited. Therefore, we aimed to perform a systematic review and meta-analysis comparing outcomes after CA for AF in patients with versus without prior or active cancer. METHODS: We systematically searched PubMed, Cochrane Library, and Embase from inception to April 2023 for studies comparing the safety and efficacy of CA for AF in cancer survivors. Outcomes of interest were bleeding events, late AF recurrence, and need for repeat ablation. Statistical analyses were performed using Review Manager 5.4.1. We pooled odds ratios (OR) with 95% confidence intervals (CI) for binary endpoints. RESULTS: We included 5 retrospective cohort studies comprising 998 patients, of whom 41.4% had a history of cancer. Cancer survivors were at significantly higher risk of clinically relevant bleeding (OR 2.17; 95% CI 1.17-4.0; p=0.01) as compared with those without cancer. The efficacy of CA for AF was similar between groups. Late AF recurrence at 12 months was not significantly different between patients with vs. without a history of cancer (OR 1.29; 95% CI 0.78-2.13; p=0.32). Similar findings were observed in the outcome of repeat ablations (OR 0.71; 95% CI 0.37-1.37; p=0.31). CONCLUSIONS: These findings suggest that cancer survivors have an increased risk of bleeding after CA for AF relative to patients without cancer, with no significant difference in the efficacy of CA for maintenance of sinus rhythm between groups. STUDY REGISTRATION: This systematic review is registered in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42023394538.

Direct oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation on chronic hemodialysis: a meta-analysis of randomized controlled trials.

PURPOSE: Patients with atrial fibrillation (AF) and end-stage renal disease on chronic hemodialysis are at risk for thromboembolic and bleeding events. We aimed to perform a meta-analysis to evaluate the safety and efficacy of direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) in this population. METHODS: We systematically searched PubMed, Excerpta Medica Database (EMBASE) and Cochrane Library for randomized controlled trials (RCTs) comparing DOACs with VKAs in patients with AF on chronic hemodialysis from inception to February 2023 in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Outcomes were reported using risk ratios (RRs) with 95% confidence intervals (CIs). Statistical analyses were performed using R version 4.2.2. RESULTS: We selected three RCTs including 341 patients, of whom 176 (51.6%) were randomized to DOACs. Follow-up ranged from 174 days to 3.38 years. There was no significant difference between groups in terms of cardiovascular mortality (RR 1.34; 95% CI 0.69-2.60; p = 0.39), all-cause mortality (RR 0.96; 95% CI 0.72-1.27; p = 0.77), ischemic/uncertain type of stroke or transient ischemic attack (RR 0.50; 95% CI 0.19-1.35; p = 0.17), or major or life-threatening bleeding (RR 0.70; 95% CI 0.39-1.25; p = 0.22). CONCLUSION: In this meta-analysis of three RCTs, no significant difference was observed between DOACs and VKAs in cardiovascular mortality, all-cause mortality, ischemic/uncertain type of stroke or transient ischemic attack, or major or life-threatening bleeding in patients with AF on chronic hemodialysis.

Coronary Computed Tomography Angiography Versus Invasive Coronary Angiography in Stable Chest Pain: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The efficacy of coronary computed tomography angiography (CCTA) versus invasive coronary angiography (ICA) among patients with stable chest pain has been studied in several trials with conflicting results. METHODS: We performed a systematic review and meta-analysis comparing CCTA first versus direct ICA among patients with stable chest pain, who were initially referred to ICA. PubMed, EMBASE, and Cochrane Central were searched for randomized controlled trials comparing the 2 strategies. Risk ratios (RRs) and mean differences with 95% CIs were computed for binary and continuous outcomes, respectively. RESULTS: Five randomized controlled trials with a total of 5727 patients were included, of whom 51.1% were referred to CCTA and 22.5% of patients had evidence of ischemia on a prior functional test. In the follow-up ranging from 1 to 3.5 years, 660 of the 2928 patients randomized to CCTA first underwent ICA (23%). Patients who underwent CCTA had lower rates of coronary revascularization (RR, 0.74 [95% CI, 0.66-0.84]; P<0.001) and stroke (RR, 0.50 [95% CI, 0.26-0.98]; P=0.043). Cardiovascular mortality (RR, 0.55 [95% CI, 0.24-1.23]; P=0.146), major adverse cardiovascular events (RR, 0.84 [95% CI, 0.64-1.10]; P=0.198), nonfatal myocardial infarction (RR, 1.09 [95% CI, 0.63-1.88]; P=0.768), and cardiovascular hospitalizations (RR, 0.91 [95% CI, 0.59-1.39]; P=0.669) did not differ significantly between groups. CONCLUSIONS: In patients with stable chest pain referred for ICA, CCTA avoided the need for ICA in 77% of patients otherwise referred for ICA. CCTA was associated with a reduction in the rates of coronary revascularization and stroke compared with direct ICA. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42023383143.

Efficacy of anti-amyloid-ß monoclonal antibody therapy in early Alzheimer's disease: a systematic review and meta-analysis.

BACKGROUND: Studies targeting amyloid-ß in patients with Alzheimer's disease (AD) have conflicting results and early initiation of therapy may yield better outcomes. METHODS: We systematically searched PubMed, Embase, Cochrane Library, and Clinicaltrials.gov for randomized trials comparing monoclonal antibodies (mAbs) with placebo in MCI or mild dementia due to AD. RESULTS: Nineteen studies comprising 15,275 patients were included. In patients with early AD, mAbs reduced the rate of decline, in both the Clinical Dementia Rating Scale, the sum of boxes (CDR-SB; MD -0.30; 95% CI -0.42,-0.19; p < 0.01), and the Alzheimer's Disease Assessment Scale, cognitive subscore (ADAS-cog; SMD -0.80; 95% CI -10.25,-0.35; p < 0.01). The results were similar between clinical stages for CDR-SB (MCI, MD -0.19; 95% CI -0.35,-0.03; p = 0.02; mild dementia, MD -0.45; 95% CI -0.65,-0.25; p < 0.01; subgroup differences, p = 0.13), as well as for ADAS-Cog (MCI, SMD -0.83; 95% CI -1.49,-0.17; p = 0.01; mild dementia, SMD -0.69; 95% CI -1.32 to -0.05; p = 0.03; subgroup differences, p = 0.47). The risk of amyloid-related imaging abnormalities (ARIA) was significantly higher in patients taking mAbs, including ARIA-edema (RR 7.7; 95% CI 4.60 to 13.00; p < 0.01), ARIA-hemorrhage (RR 1.8; 95% CI 1.22 to 2.59; p < 0.01), and symptomatic or serious ARIA (RR 14.1; 95% CI 7.30 to 27.14; p < 0.01). CONCLUSION: Anti-amyloid-ß mAbs attenuate cognitive and functional decline compared with placebo in early AD; whether the magnitude of this effect is clinically important remains uncertain, especially relative to the safety profile of these medications. Starting immunotherapy in patients with MCI was not significantly different than starting in the mild dementia stage. PROSPERO REGISTRY: CRD42023430698.

Modified Atkins diet for drug-resistant epilepsy: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the effectiveness and side-effect profile of the modified Atkins diet (MAD) compared to the usual diet (UD) in reducing seizure frequency among patients with drug-resistant epilepsy (DRE). METHODS: In February 2023, we conducted an extensive search in PubMed, EMBASE, and Cochrane databases to find randomized controlled trials (RCTs) comparing MAD to UD in patients with drug-resistant epilepsy (DRE) on standard anti-seizure medication (ASM). We used random-effects meta-analyses and the Risk of Bias 2 tool to evaluate treatment effects and assess the quality of the included RCTs, respectively. RESULTS: Six studies were evaluated in the meta-analysis, including 575 patients, of whom 288 (50.1 %) were randomized to the MAD. Average follow-up period was 12 weeks. MAD plus standard drug therapy was associated with a higher rate of 50 % or greater reduction in seizure frequency compared to UD plus drug therapy (RR 6.28; 95 % CI 3.52-10.50; p<0.001), both in children (RR 6.28; 95 % CI 3.43-11.49; p<0.001) and adults with DRE (RR 6.14; 95 % CI 1.15-32.66; p = 0.033). MAD was also associated with a higher seizure freedom rate compared to UD (RR 5.94; 95 % CI 1.93-18.31; p = 0.002). Five studies reported adverse events with MAD; constipation was reported in 17 % of patients (95 % CI 5-44 %), lethargy in 11 % (95 % CI 4-25 %), and anorexia in 12 % (95 % CI 8-19 %). Due to limited information about the ASM regimens, we were unable to further analyze the interaction between MAD and ASM. SIGNIFICANCE: This meta-analysis, comprising 575 patients from 6 RCTs, revealed that MAD led to higher rates of seizure freedom and underscored its role in seizure frequency reduction by 50 % or more in both adults and children, with no significant adverse events concerns.

Network Meta-Analysis of Initial Antithrombotic Regimens After Left Atrial Appendage Occlusion.

BACKGROUND: The optimal antithrombotic therapy following left atrial appendage occlusion (LAAO) in patients with nonvalvular atrial fibrillation (AF) remains uncertain. OBJECTIVES: In this study, the authors sought to compare the efficacy and safety of various antithrombotic strategies after LAAO. METHODS: We searched the Medline, Cochrane, EMBASE, LILACS, and ClinicalTrials.gov databases for studies reporting outcomes after LAAO, stratified by antithrombotic therapy prescribed at postprocedural discharge. Direct oral anticoagulants (DOACs), vitamin K antagonists (VKAs), single antiplatelet therapy (SAPT), dual antiplatelet therapy (DAPT), DOAC plus SAPT, VKA plus SAPT, and no antithrombotic therapy were analyzed. We performed a frequentist random effects model network meta-analysis to estimate the OR and 95% CI for each comparison. P-scores provided a ranking of treatments. RESULTS: Forty-one studies comprising 12,451 patients with nonvalvular AF were included. DAPT, DOAC, DOAC plus SAPT, and VKA were significantly superior to no therapy to prevent device-related thrombosis. DOAC was associated with lower all-cause mortality than VKA (OR: 0.39; 95% CI: 0.17-0.89; P = 0.03). Compared with SAPT, DAPT was associated with fewer thromboembolic events (OR: 0.50; 95% CI: 0.29-0.88; P = 0.02), without a difference in major bleeding. In the analysis of P-scores, DOAC monotherapy was the strategy most likely to have lower thromboembolic events and major bleeding. CONCLUSIONS: In this network meta-analysis comparing initial antithrombotic therapies after LAAO, monotherapy with DOAC had the highest likelihood of lower thromboembolic events and major bleeding. DAPT was associated with a lower incidence of thromboembolic events compared with SAPT and may be a preferred option in patients unable to tolerate anticoagulation.

Direct oral anticoagulants versus aspirin for primary thromboprophylaxis in patients with multiple myeloma undergoing outpatient therapy: A systematic review and updated meta-analysis.

Patients with multiple myeloma (MM) are at an elevated risk of venous thromboembolism (VTE), which is further increased for those undergoing anti-myeloma therapy. Current guidelines suggest low-dose direct oral anticoagulants (DOACs) as an alternative to aspirin for primary thromboprophylaxis in this population, but data comparing these two therapies are limited. We performed a systematic review and meta-analysis to compare DOACs with aspirin for primary thromboprophylaxis in individuals undergoing outpatient anti-myeloma therapy. Studies were selected when comparing DOACs versus aspirin for thrombotic and haemorrhagic outcomes. We included 10 randomised controlled trials and observational studies comprising 1026 patients with MM who received primary thromboprophylaxis with DOACs (n = 337) or aspirin (n = 689). DOAC thromboprophylaxis was associated with a significantly lower incidence of VTE compared with aspirin (OR 0.33; 95% CI 0.16-0.68; p < 0.001). Major, clinically relevant non-major and minor bleeding event rates did not differ significantly between groups. Overall, our meta-analysis suggests that DOACs may be a preferable option to aspirin for the prevention of MM-related thrombosis. However, these results should be interpreted in the context of heterogeneous baseline population characteristics and potential bias from including observational studies. Further research is needed to evaluate the optimal thromboprophylaxis strategy, particularly in high-risk individuals.

Increased Social Support Reduces the Incidence of Motoric Cognitive Risk Syndrome.

Background and Objectives: The motoric cognitive risk syndrome (MCR) is a predementia syndrome characterized by slow gait and cognitive complaint. The relationship between MCR and social support-a potentially modifiable risk factor of dementia-is currently unknown. The current study aimed to determine whether MCR incidence varies as a function of social support in aging. Research Design and Methods: We examined MCR incidence in 506 community-dwelling older adults (M Age 76.59; 57.3% female) without MCR or dementia at baseline. We quantified perceived levels of social support with the Medical Outcomes Study Social Support Survey, incorporating four different categories of support: (a) emotional/informational support, (b) tangible support, (c) affectionate support, and (d) positive social interactions. We used Cox regression analyses, adjusted for age, sex, race/ethnicity, education, marital status, comorbidities, and global cognition, to estimate hazard ratios (aHR) with 95% confidence intervals (CIs). Results: Over a median follow-up time of 2.5 years (range = 1-7 years), 38 participants (9.8%) developed MCR. Increased tangible support decreased the risk of MCR by 30% (aHR: 0.70, 95% CI: 0.53-0.92, p = .011). Increased overall social support decreased the risk of MCR by 33% (aHR: 0.67, 95% CI: 0.46-0.98, p = .038). Other subcategories of social support were not associated with a decreased risk of MCR (p > .05). Discussion and Implications: Higher levels of tangible social support, as well as overall social support, were associated with reduced risk for MCR in older adults. Increasing social support may be a promising avenue of intervention for reducing the risk of MCR, dementia, and other forms of cognitive decline.

Maternal Outcomes in Women with Peripartum Cardiomyopathy versus Age and Race-Matched Peers in an Urban US Community.

Peripartum cardiomyopathy (PPCM) is idiopathic systolic congestive heart failure around pregnancy. Comparisons with matched controls are lacking. We investigated maternal characteristics and outcomes up to 12 months in a cohort admitted to Montefiore Health System in Bronx, New York 1999−2015 (n = 53 cases and n = 92 age and race-matched controls, >80% Black or Hispanic/Latina). Compared to peers, women with PPCM had more chronic hypertension (24.5% vs. 8.8%, p = 0.001), prior gestational hypertension (20.8% vs. 5.4%, p = 0.001), prior preeclampsia (17.0% vs. 3.3%, p = 0.001), familial dilated cardiomyopathy (5.7% vs. 0.0%, p = 0.04), smoking (15.1% vs. 2.2%, p = 0.001), lower summary socioeconomic scores (−4.12 (IQR −6.81, −2.13) vs. −1.62 (IQR −4.20, −0.74), p < 0.001), public insurance (67.9% vs. 29.3% p = 0.001), and frequent depressive symptoms. Women with PPCM were often admitted antepartum (34.0% vs. 18.5%, p = 0.001) and underwent Cesarean section (65.4% vs. 30.4%, p = 0.001), but had less preterm labor (27.3% vs. 51.1%, p = 0.001). Women were rarely treated with bromocriptine (3.8%), frequently underwent left ventricular assist device placement (9.4% and n = 2 with menorrhagia requiring transfusion and progesterone) or heart transplantation (3.8%), but there were no in-hospital deaths. In sum, women with PPCM had worse socioeconomic disadvantage and baseline health than matched peers. Programs addressing social determinants of health may be important for women at high risk of PPCM.