Obese patients with atrial fibrillation are more efficiently protected from thrombosis under warfarin or xabans compared to non-obese patients; a systematic review and Meta-analysis of six randomized controlled trials.

INTRODUCTION: Recommendations about proper anticoagulation in obese patients, body mass index (BMI) > 30 kg/m2, are not yet clearly defined. Obese patients were included in randomized controlled trials comparing new anticoagulants (NOACs) with warfarin in patients with atrial fibrillation or thromboembolism. METHODS: We performed a medline search entering proper criteria and finally 6 post-hoc analysis of RCTs, reporting outcome according to BMI, were included in this meta-analysis. Two major outcomes were considered end points in our meta-analysis; thrombosis, including ischemic cerebral events (transient or not) and venous thrombosis (DVD) /pulmonary embolism (PE) and bleeding, including major bleeding and clinically relevant non-major bleeding. RESULTS: In the NOACs treated group, thrombosis occurred less frequently in obese vs non-obese patients; RR and 95 % CI 0,75 (0,58-0,97), p = 0,03, while low heterogeneity was observed (I2= 40 %). In the warfarin treated subgroup there was statistically significant difference with less thrombotic events occurring in the obese vs non-obese patients; RR and (95 % CI) 0,80 (0,66-0,98), p = 0,03, and heterogeneity was low (I2 = 24 %). This protective effect called the obesity paradox is limited to obese patients anticoagulated for non-valvular atrial fibrillation (NVAF); RR (95 % CI) was 0,70 (0,58-0,85) p = 0,03 and I2 = 24 %. Bleeding events were similar under both NOACs and warfarin in obese vs non-obese analysis. CONCLUSIONS: Obese patients anticoagulated for NVAF with either standard dose of xabans or INR guided warfarin are more efficiently protected against thrombosis compared to non-obese patients.

How to improve RCHOP as frontline therapy for diffuse large B-cell lymphoma: a systematic review and meta-analysis of 21 randomized controlled trials.

RCHOP is the standard of care for patients with diffuse large b-cell lymphoma (DLBCL) but failures occur in approximately 40% of them. We performed a meta-analysis of 21 randomized controlled trials (RCTs) comparing experimental regimens with RCHOP. We searched the database of PubMed with proper criteria, and data of efficacy (Progression Free Survival-PFS) in the ITT population were extracted and analyzed. Cross comparisons of RCTs were performed by using the CINEMA software. Odds ratio (OR) and 95% confidence intervals (95%, CI) are reported. The literature search yielded 21 RCTs including 5785 patients in the RCHOP arm and 5648 patients in the experimental arm. Odds ratio (OR) for PFS in the total cohort was OR (95%, CI): 0.87 (0.76-0.99), p=0.02. Among different strategies to improve RCHOP, addition of a novel agent on RCHOP improved PFS. In total 1740 patients in the RCHOP arm were compared with 1755 in the RCHOP plus a novel agent arm, and the OR (95% CI) for PFS was 0.84 (0.71-0.97), p=0.02. Indirect comparisons of nine studies adding a novel agent on RCHOP does not give prominence to any agent. Subgroup analysis according to cell of origin was performed for non-GC DLBCL patients. In this subgroup, 1546 patients treated with RCHOP were compared with 1538 patients treated with experimental regimens. The OR (95% CI) for PFS was 0.86 (0.73-1.02), p=0.34. Overall survival data extracted from 18 studies showed no superiority of experimental regimens over RCHOP. Efficacy of RCHOP backbone is marginally improved when adding a novel anti-lymphoma agent.

Apixaban reduces the risk of major and clinically relevant non-major bleeding compared to warfarin in patients with end stage renal disease; a systematic review and meta-analysis of ten studies.

Optimal anticoagulation in patients with end-stage renal disease ESRD is a matter of debate since these patients are not included in randomized controlled trials (RCTs). Evolving data are in favor of apixaban compared to warfarin. METHODS: We extracted data from 2 RCTs, 5 retrospective cohort studies and 3 large data-based studies. Both dosing regimens of apixaban, standard or reduced, were accepted. In most studies characteristics of patients were balanced between arms. Patients with either atrial fibrillation (AF) or venous thromboembolism (VTE) were included. Quality of studies was graded as high and the funnel plot did not detect any publication bias. In total we analyzed the outcome of 6693 ESRD patients treated with apixaban and 19,836 treated with warfarin. Our analysis was performed by using the random effects model. We report our data as Risk Ratio (RR) and associated 95 % confidence interval values (95 %, CI). RESULTS: The RR (95 % CI) of major bleeding was 0.69 (0.57-0.84) p = 0.0002 in favor of apixaban vs warfarin with heterogeneity to be statistically significant I2 63% p = 0.004. Meta-regression analysis with year of publication as moderator shows in bubble plotting that studies published earlier than 2018 were plotted as outliers. The RR (95 % CI) of clinically relevant non-major bleeding (CRNMB) was 0.74 (0.64-0.87) p = 0.0002 favoring again apixaban. Standard apixaban dose over reduced dose is less hemorrhagic compared to warfarin. Overall, in our study the risk of thrombosis in both arms was statistically non-different. CONCLUSIONS: In our study we observed less hemorrhagic events with apixaban in ESRD patients compared to warfarin.

P-wave duration and interatrial block as predictors of new-onset atrial fibrillation: A systematic review and meta-analysis.

BACKGROUND: Early detection of atrial fibrillation (AF) could improve patient outcomes. P-wave duration (PWD) and interatrial block (IAB) are known predictors of new-onset AF and could improve selection for AF screening. This meta-analysis reviews the published evidence and offers practical implications. METHODS: Publication databases were systematically searched, and studies reporting PWD and/or morphology at baseline and new-onset AF during follow-up were included. IAB was defined as partial (pIAB) if PWD≥120 ms or advanced (aIAB) if the P-wave was biphasic in the inferior leads. After quality assessment and data extraction, random-effects analysis calculated odds ratio (OR) and confidence intervals (CI). Subgroup analysis was performed for those with implantable devices (continuous monitoring). RESULTS: Among 16,830 patients (13 studies, mean 66 years old), 2,521 (15%) had new-onset AF over a median of 44 months. New-onset AF was associated with a longer PWD (mean pooled difference: 11.5 ms, 13 studies, p < 0.001). The OR for new-onset AF was 2.05 (95% CI: 1.3-3.2) for pIAB (5 studies, p = 0.002) and 3.9 (95% CI: 2.6-5.8) for aIAB (7 studies, p < 0.001). Patients with pIAB and devices had higher AF-detection risk (OR: 2.33, p < 0.001) than those without devices (OR: 1.36, p = 0.56). Patients with aIAB had similarly high risk regardless of device presence. There was significant heterogeneity but no publication bias. CONCLUSION: Interatrial block is an independent predictor of new-onset AF. The association is stronger for patients with implantable devices (close monitoring). Thus, PWD and IAB could be used as selection criteria for intensive screening, follow-up or interventions.

P-wave duration and atrial fibrillation recurrence after catheter ablation: a systematic review and meta-analysis.

AIMS: Atrial fibrillation (AF) is a global health problem with high morbidity and mortality. Catheter ablation (CA) can reduce AF burden and symptoms, but AF recurrence (AFr) remains an issue. Simple AFr predictors like P-wave duration (PWD) could help improve AF therapy. This updated meta-analysis reviews the increasing evidence for the association of AFr with PWD and offers practical implications. METHODS AND RESULTS: Publication databases were systematically searched and cohort studies reporting PWD and/or morphology at baseline and AFr after CA were included. Advanced interatrial block (aIAB) was defined as PWD ≥ 120 ms and biphasic morphology in inferior leads. Random-effects analysis was performed using the Review Manager 5.3 and R programs after study selection, quality assessment, and data extraction, to report odds ratio (OR) and confidence intervals. : Among 4175 patients in 22 studies, 1138 (27%) experienced AFr. Patients with AFr had longer PWD with a mean pooled difference of 7.8 ms (19 studies, P < 0.001). Pooled OR was 2.04 (1.16-3.58) for PWD > 120 ms (13 studies, P = 0.01), 2.42 (1.12-5.21) for PWD > 140 ms (2 studies, P = 0.02), 3.97 (1.79-8.85) for aIAB (5 studies, P < 0.001), and 10.89 (4.53-26.15) for PWD > 150 ms (4 studies, P < 0.001). There was significant heterogeneity but no publication bias detected. CONCLUSION: P-wave duration is an independent predictor for AF recurrence after left atrium ablation. The AFr risk is increasing exponentially with PWD prolongation. This could facilitate risk stratification by identifying high-risk patients (aIAB, PWD > 150 ms) and adjusting follow up or interventions.

Socioeconomic Status is Globally a Prognostic Factor for Overall Survival of Multiple Myeloma Patients: Synthesis of Studies and Review of the Literature.

BACKGROUND: Socioeconomic status (SES) is reflecting differences in sociodemographic factors affecting cancer survivorship. Deprived, low SES populations have a higher prevalence of multiple myeloma and worst survival, a condition which widens over time. METHODS: We performed a meta-analysis of 16 studies (registries and cohorts) reporting myeloma patients' survival data according to SES. Ten studies reported Hazzard Ratio (H.R.) (95 % CI), and 16 studies reported p values. We combined the H.R. from 10 studies, and by using the Mosteller-Bush formula, we performed a synthesis of p values according to the area of the globe. RESULTS: Combination of H.R. from 10 studies including 85198 myeloma patients weighted to sample size of each study and adopting the hypothesis of random effect returned a combined H.R.: 1,26 (1,13-1,31) in favor of high SES patients.USA: Synthesis of p values coming from 6 studies (n=89807 pts) by using the Mosteller and Bush formula extracted a p-value of <0.0001 favoring high SES patients.Oceania: Synthesis of p values in two cohorts from Australia and New Zealand (n= 10196 pts) returned a p-value of 0,022 favoring high SES patients.Europe: The synthesis of p values from the U.K. and Greece studies (n=18533 pts) returned a p-value of <0,0001 favoring high SES patients.Asia: Synthesis of 2 studies from Asia (n=915 pts) returned a p-value of <0,0001 favoring high SES patients. CONCLUSIONS: Across the globe and widening over decades, the socioeconomic status remains a gap for equality in myeloma care.

Hold your needles in women with recurrent pregnancy losses with or without hereditary thrombophilia: Meta-analysis and review of the literature.

OBJECTIVES: The use of antithrombotic prophylaxis in women with recurrent pregnancy losses (RPL) remains controversial. METHODS: We performed meta-analysis of randomized controlled trials (RCTs) comparing low molecular weight heparin (LMWH) versus No LMWH in women with or without hereditary thrombophilia and RPL. Twelve RCTs met our inclusion criteria and 2298 women were included in this meta-analysis. Our primary end point was live birth and odds ratio (OR) for live birth are reported. RESULTS: In women with thrombophilia the benefit of LMWH on live birth is not significant but heterogeneity of the studies is significant (OR, 2.09; 95 % CI, 0.58-7.57; p = 0.26; I2 = 86 %, p = 0.0001). Considering women without thrombophilia there is no benefit of LMWH in OR of live birth and data from studies have low heterogeneity (OR, 1.25; 95 % CI, 0.88-1.78; p = 0 0.21; I2 = 44 %, p = 0.07). CONCLUSIONS: Hold your needles in women with RPL. Probably in some hereditary thrombophilic defects LMWH has a positive effect on OR for live birth.

Socioeconomic Status Is an Independent Prognostic Factor for Overall Survival in Patients With Multiple Myeloma: Real-World Data From a Cohort of 223 Patients.

INTRODUCTION: Socioeconomic status (SES) has been shown to be a prognostic factor for overall survival in a variety of hematologic malignancies, especially for patients who require continuous care such as those with multiple myeloma (MM). PATIENTS AND METHODS: We retrospectively collected data from 223 patients with symptomatic MM diagnosed and treated in our department from January 2005 to December 2019. The modified Kuppuswamy scale, slightly modified, was used for the SES assessment. The Kaplan-Meier estimator of survival and Cox regression analysis were used. RESULTS: In our cohort of 223 patients with MM, low SES was an independent poor prognostic factor for overall survival (OS), in addition to higher International Staging System stage and high-risk cytogenetics (hazard ratio for low SES on Cox regression analysis, 2.092; 95% confidence interval [CI], 1.36-3.2; log-rank P = .000). Patients with low SES had inferior survival compared with the whole patient cohort (median OS: low SES, 28 months; 95% CI, 18-37.9; high SES, 68 months; 95% CI, 55.6-80.4; log-rank P = .000). The low SES effect on OS was more evident for the elderly patients who were not transplant eligible and in those with a diagnosis of MM International Staging System stage I. The effect of low SES on OS was attenuated by time, and ethnic origin had no effect on OS. CONCLUSIONS: The results of the present study have shown that low SES is an independent poor prognostic factor for survival of patients with MM.