Fixed-effects Meta-analysis Research Articles

Abstract 4145889: Association between Pulmonary Artery Elastance and all cause mortality in patients with Heart Failure: A Meta-Analysis

Background: Pulmonary Artery Elastance (PAE) is an echocardiographic value commonly calculated in Heart Failure (HF) patients. It is presumed to be associated with mortality and adverse outcomes. We aim to evaluate pulmonary artery elastance (PAE) as a predictor of all-cause mortality in heart failure (HF) patients Methods: A comprehensive literature review was conducted on PubMed and Google Scholar from inception till May 2024 for articles relevant to the mortality outcomes in HF patients with respect to pulmonary arterial elastance as one of their predictors. Data were extracted independently by four different reviewers. We used a fixed-effects model meta-analysis model to evaluate and pool the outcomes in association with PAE and all-cause mortality. Further assessment of the outcomes was performed by sensitivity analysis with a one-study removal method and meta-regression analysis. Results: Out of 63 studies, 4 studies with 759 patients were included in our meta-analysis. Mean age ranged from 54 to 65 years. We found there was a statistically significant association between pulmonary artery elastance and all-cause mortality (OR: 1.12, 1.06 - 1.19, p < 0.0001] (Figure 1a). Sensitivity analysis with one-study removal showed overall effects in the meta-analysis still lean towards supporting PAE as the predictor for ACM (Figure 1b). Meta-regression analysis with age (Figure 1c), sex and other supportive variables did not show statistically significant associated confounders. Conclusion: This meta-analysis establishes a significant association between elevated PAE and increased risk for all-cause mortality in HF patients. These results suggest PAE could be a strong predictor for all-cause mortality in HF patients. Further research is needed to provide a more comprehensive understanding of the predictive value of PAE for HF patients. The association between PAE and mortality could provide significant insights that could influence clinical practice and improve patient outcomes in HF.

Invasive Versus Conservative Strategy in Older Adults ≥75 Years of Age With Non-ST-segment-Elevation Acute Coronary Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Older adults with non-ST-segment-elevation acute coronary syndrome are less likely to undergo an invasive strategy compared with younger patients. Randomized controlled trials traditionally exclude older adults because of their high burden of geriatric conditions. We searched for randomized controlled trials comparing invasive versus medical management or a selective invasive (conservative) strategy for older patients (age≥75 years) with non-ST-segment-elevation acute coronary syndrome. Fixed effects meta-analysis was conducted to estimate the odds ratio (OR) with 95% CI for the composite of death or myocardial infarction (MI) and individual secondary end points of all-cause death, cardiovascular death, MI, revascularization, stroke, and major bleeding. Nine studies with 2429 patients (invasive: 1228 versus control: 1201) with a mean follow-up of 21 months were included. An invasive strategy was associated with a significantly decreased risk of a composite of death and MI (OR, 0.67 [95% CI, 0.54-0.83], P<0.001), MI (OR, 0.56 [95% CI, 0.45-0.70], P<0.001) and subsequent revascularization (OR, 0.27 [95% CI, 0.16-0.48], P<0.001). There was no difference in all-cause death (OR, 0.84 [95% CI, 0.65-1.10], P=0.21), cardiovascular death (OR, 0.85 [95% CI, 0.63-1.15], P=0.30), stroke (OR, 0.74 [95% CI, 0.38-1.47], P=0.39), or major bleeding (OR, 1.24 [95% CI, 0.42-3.66], P=0.70). In older patients ≥75 years old with non-ST-segment-elevation acute coronary syndrome, an invasive strategy reduced the risk of a composite of death and MI, MI, and subsequent revascularization compared with a conservative strategy alone. Older adults with higher burden of geriatric conditions should be included in future trials to improve generalizability to this growing population.

Coffee and Risk of Pancreatic Cancer: Insights from Two-Sample and Multivariable Mendelian Randomization Analyses.

The association between coffee and pancreatic cancer risk has reported inconsistent results. Therefore, a Mendelian randomization (MR) study was undertaken to investigate the association between coffee and pancreatic cancer from a genetic perspective. In East Asian and European populations, independent genetic variants strongly associated with coffee were chosen as instrumental variables (IVs) from relevant genome-wide association studies (GWASs). GWAS data for pancreatic cancer were obtained from the JENGER (Japanese Encyclopedia of Genetic Associations by Riken) project and GWAS catalog database. Two-sample (TSMR) and multivariable Mendelian randomization (MVMR) analyses were conducted to investigate the genetically predicted causal relationship between coffee consumption and pancreatic cancer. A fixed-effect meta-analysis was employed to aggregate estimates from the two populations to reveal the overall association. Both in East Asian and European populations, an increase in coffee intake of a cup per day was not associated with pancreatic cancer risk, regardless of coffee type (including caffeine drinks, instant coffee, decaffeinated coffee, ground coffee, etc.). The results aligned with the findings of the meta-analysis (OR = 1.100, 95%CI = 0.862-1.403, p = 0.450). Also, for coffee intake with positive results in the TSMR analysis (OR = 1.739, 95%CI 1.104-2.739, p = 0.017), consistent negative results were observed after adjusting for potential confounders (smoking traits, drinking, type 2 diabetes, body mass index) in the MVMR analyses. This study found no genetically predicted causal relationship between coffee consumption and pancreatic cancer risk.

Prophylactic antibiotics for manual removal of retained placenta in vaginal birth.

Retained placenta is a potentially life-threatening condition because of its association with postpartum haemorrhage. Manual removal of the placenta increases the likelihood of infectious complications of the uterine cavity. So, prophylactic antibiotics are recommended by some experts, and commonly administered to reduce these risks. However, the evidence supporting this decision is limited. This review aims to assess the effectiveness of prophylactic antibiotics for manual removal of retained placenta after vaginal birth. To compare the effectiveness and adverse effects of routine prophylactic antibiotics for the manual removal of placenta after vaginal birth. To identify appropriate prophylactic antibiotic regimens. For this update, we searched CENTRAL, MEDLINE, Embase, CINAHL, and two trials registries, in addition to screening the reference lists of retrieved studies and systematic reviews. The last search was 14 May 2024. All randomised controlled trials and non-randomised studies comparing prophylactic antibiotics to no treatment or to another prophylactic antibiotic to prevent postpartum endometritis after manual removal of placenta after vaginal birth. The critical outcome in our review was postpartum endometritis. Other important outcomes were puerperal morbidity, perineal infection, duration of hospital stay, sepsis, any infection, blood loss, postpartum haemorrhage, secondary postpartum haemorrhage, readmission to hospital, adverse effects of the drugs, women's satisfaction, and neonatal outcomes, such as jaundice, sepsis, neonatal intensive care unit admission, et cetera. The risk of bias was assessed at the outcome level. We used the Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I) tool to assess the risk of bias in non-randomised studies. We carried out statistical analysis using Review Manager. We used a fixed-effect meta-analysis to synthesise the results, and GRADE to assess the certainty of the evidence. We included four retrospective cohort studies with a total of 974 participants. Studies were conducted in Germany, Bulgaria, Norway, and Israel, between 1983 and 2017. Prophylactic antibiotics versus no antibiotics was the only comparison in our analysis. Postpartum endometritis We do not know whether prophylactic antibiotics have an impact on postpartum endometritis (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.48 to 1.85; 4 studies, 974 participants; very low-certainty evidence). Postpartum haemorrhage The evidence suggests that prophylactic antibiotics may result in little to no difference in postpartum haemorrhage (RR 1.00, 95% CI 0.78 to 1.29; 1 study, 325 participants; low-certainty evidence). Neonatal intensive care unit admission (NICU) The evidence suggests that prophylactic antibiotics may result in little to no difference in NICU admission of the neonate (RR 0.86, 95% CI 0.29 to 2.61; 1 study, 353 participants; low-certainty evidence). There were no data available for other important outcomes, including puerperal morbidity, perineal infection, duration of hospital stay, sepsis, any infection, blood loss, secondary postpartum haemorrhage, readmission to hospital, adverse effects of drugs, women's satisfaction, or neonatal outcomes of jaundice or sepsis. There is very uncertain evidence supporting the use of prophylactic antibiotics for manual removal of placenta for preventing postpartum endometritis. The evidence suggests that prophylactic antibiotics result in little to no difference in postpartum haemorrhage or admission to a neonatal intensive care unit. There were no available data on other important outcomes. Multicentre, randomised controlled trials comparing antibiotic prophylaxis and placebo or no antibiotic, or one antibiotic and another, for manual removal of placenta in vaginal birth are needed to provide more robust evidence. This systematic review received support from the UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP). Protocol and previous versions are available at https://10.1002/14651858.CD004904.pub3.

A systematic review and meta-analysis of the efficacy and safety of combined mechanical circulatory support in cardiogenic shock complicating acute myocardial infarction

Abstract Background Cardiogenic shock complicating acute myocardial infarction (CSAMI) is a severe complication associated with unacceptably high mortality rates. Since early revascularisation was introduced more than 20 years ago, no subsequent innovation has demonstrated conclusive efficacy in reducing mortality in CSAMI. While mechanical circulatory support (MCS) has emerged as a potential intervention, randomised controlled trials evaluating independent use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO), and intra-aortic balloon pump (IABP) have not shown benefit in CSAMI. In contrast, systematic reviews of observational studies have revealed significant mortality reduction when CSAMI was treated with combined use of MCS, specifically VA-ECMO in conjunction with a left ventricular (LV) unloading device (Impella or IABP). Combination MCS (VA-ECMO + LV unloading) may therefore present a promising approach to CSAMI, but an unresolved dilemma concerning the optimal selection between two LV unloading devices (VA-ECMO + Impella vs VA-ECMO + IABP) warrants further investigation and clarification. Purpose We perform the first systematic review and meta-analysis assessing the short-term efficacy and safety of VA-ECMO + Impella versus VA-ECMO + IABP in treatment of CSAMI. Methods A systematic search was performed on the EMBASE and MEDLINE databases. Studies reporting the short-term (30-day/inpatient) mortality and complications of adult patients with CSAMI treated with VA-ECMO + Impella and VA-ECMO + IABP were included. Fixed effect meta-analyses using Mantel-Haenszel model was used to analyse the pooled odds ratio for short-term mortality and major complications. Subgroup analysis was performed including studies with ACS predominant CS (Cause of CS 100% by AMI). Results Four observational studies with 14,247 patients were included. These studies showed high heterogeneity for the total CSAMI cohort and low heterogeneity for the ACS predominant cohort. There was no significant difference in mortality between VA-ECMO + Impella and VA-ECMO + IABP 56.5% vs 66.5%; OR, 0.90; 95% CI, 0.79–1.02; P=0.09. However, VA-ECMO + Impella was associated with significantly lower mortality in patients with ACS predominant CS 53.2% vs 67.7%; OR, 0.72; 95% CI, 0.62–0.85; P&amp;lt;0.0001. VA-ECMO + Impella was associated with significantly higher risk of major bleeding 15.1% vs 8.6%; OR, 1.87; 95% CI, 1.50–2.32; P&amp;lt;0.00001 and vascular complications 15.0% vs 6.7%; OR, 1.75; 95% CI, 1.41–2.18; P&amp;lt;0.00001. Conclusions When comparing LV unloading devices in patients with CSAMI requiring combination MCS, VA-ECMO + Impella was superior in mortality reduction only in the cohort where 100% of CS was caused by AMI. Concomitantly, VA-ECMO + Impella was associated with greater risk of major bleeding and vascular complications. Additional randomised studies are needed to validate and strengthen the findings presented in these observational data.Forrest plot on short-term mortalityForrest plot on major complications

Blood pressure lowering efficacy of antihypertensive drugs and their combinations: a systematic review and meta-analysis of 500 randomised, double-blind placebo-controlled trials

Abstract Background Each 1 mmHg reduction in systolic blood pressure (SBP) reduces the risk of major cardiovascular disease events by about 2%. However, there are currently no tools to provide randomised trial-derived estimates of blood pressure (BP)-lowering efficacy of different antihypertensive regimens despite the vast number of possible drug-dose permutations. There has also been no attempt to classify efficacy of treatment regimens into low, moderate, and high intensity. Purpose We aimed to quantify the BP-lowering efficacy of the five major classes of antihypertensive drugs and their combinations. Methods We conducted a systematic review and meta-analysis of randomised double-blind placebo-controlled trials. CENTRAL, MEDLINE and Epistimonikos were searched from inception until December 2022 to identify trials, that compared angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers, beta-blockers, calcium channel blockers, and diuretics versus placebo, for 4-26 weeks. Primary outcomes were reduction in SBP and diastolic blood pressure (DBP). Doses were classified into standard dose based on the World Health Organisation Defined Daily Dose. BP-lowering efficacy was estimated for each drug and dose using fixed-effects meta-analyses and meta-regressions, standardised to baseline SBP 154 mmHg. Treatment regimens were categorised into low, moderate, and high intensity according to estimated SBP-lowering efficacy of &amp;lt;10, 10-19 and ≥20 mmHg, respectively. Results A total of 500 trials (106,358 participants, 44% female) were included, which included 66 single antihypertensive drugs (monotherapy) and 89 two drug (dual) combinations. The mean baseline BP was 154/100 mmHg and mean follow-up was 8.6 weeks. Monotherapy at one standard dose reduced SBP by 8.5 (95% CI, 8.2-8.9) mmHg, with an additional 1.2 (1.0-1.5) mmHg reduction for each 10 mmHg higher pre-treatment SBP, and an additional 1.5 (1.2-1.8) mmHg reduction with each doubling in dose. There was significant heterogeneity between monotherapies, and 72% were classified as low intensity efficacy. Dual combinations at one standard doses of both the drugs reduced SBP by 15.2 (13.4-17.1) mmHg, and an additional 2.6 (1.4-3.8) mmHg reduction with doubling the doses of both the drugs. There was considerable heterogeneity between dual combinations and 59% were classified as moderate, and 11% as high intensity efficacy. The BP lowering efficacy of adding additional drug classes was confirmed to be additive after accounting for pre-treatment SBP. Triple combinations were classified as high intensity efficacy based on meta-regression analyses. Conclusions There is significant variability in the efficacy of different BP-lowering regimens. The present analyses, available in an online tool, can estimate the BP lowering efficacy for any combination of drug(s) and dose(s), and can classify treatment regimens into low, moderate or high intensity.

Effectiveness of combined physical exercise and cognitive training in older adults with cognitive impairment: A systematic review and meta-analysis

Falls among cognitively impaired older adults are a global concern. The aim of this study was to assess the efficacy of combining physical exercise and cognitive training to improve balance among older adults. A systematic search of databases, including Embase, Medline-OVID, CINAHL-EBSCOhost, and Central-Cochrane Library, was conducted from March 9 to April 6, 2023. The search used keywords based on the PICO question, where the population was older adults with cognitive impairment. Compared to a single therapy, the intervention involved a combination of muscle strengthening and cognitive therapy, with the outcome of falls or balance. Inclusion criteria were randomized controlled trials (RCTs) in any setting. Studies with participants under 60 years old and lacking baseline clinical assessments were excluded. EndNote 20 was used as a reference manager tool, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 flow diagram was used to map out the number of identified records. Two investigators worked independently, and the Jadad scale was used for critical appraisal. The PROSPERO registration number is CRD42023454876. A fixed-effects meta-analysis was performed using an inverse-variance method. Four articles met the inclusion criteria, three of which were included in the meta-analysis. Studies were from Europe, New Zealand, and the Philippines, with a total sample of 255 participants and mean ages of 65.9–87.5 years. The studies used combined physical and cognitive training in one group. Results showed a significant moderate effect size (effect size (ES): 2.29; standardized mean difference (SMD): 0.41; p&lt;0.05; heterogeneity (I2): 0%) indicating no heterogeneity. In conclusion, the combined intervention displayed the potential to improve balance for cognitively impaired older adults.

A tutorial on aggregating evidence from conceptual replication studies using the product Bayes factor.

The product Bayes factor (PBF) synthesizes evidence for an informative hypothesis across heterogeneous replication studies. It can be used when fixed- or random effects meta-analysis fall short. For example, when effect sizes are incomparable and cannot be pooled, or when studies diverge significantly in the populations, study designs, and measures used. PBF shines as a solution for small sample meta-analyses, where the number of between-study differences is often large relative to the number of studies, precluding the use of meta-regression to account for these differences. Users should be mindful of the fact that the PBF answers a qualitatively different research question than other evidence synthesis methods. For example, whereas fixed-effect meta-analysis estimates the size of a population effect, the PBF quantifies to what extent an informative hypothesis is supported in all included studies. This tutorial paper showcases the user-friendly PBF functionality within the bain R-package. This new implementation of an existing method was validated using a simulation study, available in an Online Supplement. Results showed that PBF had a high overall accuracy, due to greater sensitivity and lower specificity, compared to random-effects meta-analysis, individual participant data meta-analysis, and vote counting. Tutorials demonstrate applications of the method on meta-analytic and individual participant data. The example datasets, based on published research, are included in bain so readers can reproduce the examples and apply the code to their own data. The PBF is a promising method for synthesizing evidence for informative hypotheses across conceptual replications that are not suitable for conventional meta-analysis.

Hematopoietic stem cell transplantation therapy for refractory' Crohn disease: A systematic review and meta-analysis.

Despite the availability of numerous treatments for Crohn disease, there are patients who do not respond to any therapy, thereby diminishing their quality of life. The aim of this review is to analyze the efficacy and safety of autologous hematopoietic stem cell transplantation therapy for refractory Crohn disease. This work is a systematic review with meta-analysis conducted in accordance with the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analyses. Electronic databases such as PubMed, Scopus, Web of Science, and ClinicalTrials were consulted. The searches were carried out in August 2024. To evaluate the efficacy of autologous hematopoietic stem cell transplantation in inducing remission, the mean and standard deviation of the Crohn's Disease Activity Index pre- and post- treatment were used, and a fixed-effects meta-analysis was conducted. Additionally, to assess the efficacy in perianal fistulas, a random-effects meta-analysis was performed, collecting data on the number of subjects with fistulas at the beginning and end of the intervention. All 95% confidence intervals were calculated, and the I2 statistic was used to assess the heterogeneity of the outcome variables. A total of 609 records were identified from databases, with 12 studies selected for inclusion in the review. Immediate intervention proved effective in inducing a decrease in the Crohn Disease Activity Index compared to late intervention with conventional therapies. Moreover, the meta-analysis demonstrated efficacy for Crohn disease and associated fistulas with a mean decrease in the CDAI of -217.53 ± 14.3. When evaluating the efficacy of the procedure in perianal fistulas, a risk ratio of 0.47 with a 95% CI of [0.26, 0.86] was obtained. However, the procedure showed adverse effects, such as infections, acute renal failure or deaths. Systemic autologous hematopoietic stem cell transplantation has shown efficacy in patients who fail to achieve remission of their Crohn disease with conventional therapies. This procedure has also demonstrated efficacy in treating perianal fistulas. However, it is essential to carefully evaluate de implementation of this procedure due to the associated risks.

Decolonization strategies for ESBL-producing or carbapenem-resistant Enterobacterales carriage: a systematic review and meta-analysis

The prevalence of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) and carbapenem-resistant Enterobacterales (CRE) has become a global public health problem. ESBL-E/CRE colonization can increase the risk of infection in patients and lead to poor disease prognosis. We conducted a systematic review and meta-analysis to evaluate current decolonization strategies regarding ESBL-E/CRE and their efficacy. A literature search was conducted until August 2023 on the five databases to review decolonization strategies associated with ESBL-E/CRE. A meta-analysis was conducted using RevMan 5.4 to compare differences in the decolonization strategy with placebo controls. The primary outcome was decolonization rates, with secondary outcomes of attributable death and adverse events. Quality of identified studies was determined using the Newcastle–Ottawa scale and cochrane risk assessment tool. Random and fixed effects meta-analyses were performed to calculate pooled value. A total of 25 studies were included. In five randomized controlled trial (RCT) studies, the decolonization effect of selective digestive decontamination(SDD) on ESBL-E/CRE at the end of treatment was significantly better in the experimental group than the controls [risk radio (RR): 3.30; 95% CI 1.78–6.14]. In three n-RCT studies, the decolonization effect in the experimental group was still better than the controls one month after SDD therapy [odds ratio (OR): 4.01; 95% CI 1.88–8.56]. The combined decolonization rates reported by six single-arm trial studies of SDD therapy ranged from 53.8 to 68.0%. Additionally, TSA analysis confirmed the effectiveness of SDD therapy. In studies on Faecal microbiota transplantation (FMT) therapy, the decolonization effect of the experimental group was significantly better than the controls 1 month after treatment (OR: 2.57; 95% CI 1.07–6.16). In studies without a control group and with varying follow-up times, the decolonization rates varied widely but indicated the effectiveness trend of FMT therapy (61.3–81.2%). Currently, research on the decolonization effect of probiotic therapy on ESBL-E/CRE is insufficient, and only a systematic review was conducted. SDD and FMT strategies have short-term benefits for ESBL-E/CRE decolonization, but long-term effects are unclear. The effect of probiotic therapy on ESBL-E/CRE decolonization is an interesting topic that still requires further investigation.

The Role of Different Feedback Devices in the Survival of Patients in Cardiac Arrest: Systematic Review with Meta-Analysis

Background: Cardiac arrest is a critical condition affecting approximately 1 in every 1000 people in Europe. Feedback devices have been developed to enhance the quality of chest compressions during CPR, but their clinical impact remains uncertain. This study aims to evaluate the effect of feedback devices on key clinical outcomes in adult patients experiencing both out-of-hospital (OHCA) and in-hospital cardiac arrest (IHCA). The primary objective is to assess their impact on the return of spontaneous circulation (ROSC); secondary objectives include the evaluation of neurological status and survival to discharge. Methods: A systematic review was conducted following PRISMA guidelines, utilizing databases including PubMed, Scopus, Web of Science, and Embase. Studies published between 2000 and 2023 comparing CPR with and without the use of feedback devices were included. A fixed-effects network meta-analysis was performed for ROSC and survival, while a frequentist meta-analysis was conducted for neurological outcomes. Results: Twelve relevant studies met the inclusion criteria. The meta-analysis results showed that the use of audiovisual feedback devices significantly increases the likelihood of ROSC (OR 1.26, 95% CI 1.13–1.41, p &lt; 0.0001) and survival (OR 1.52, 95% CI 1.27–1.81, p &lt; 0.0001) compared to CPR without feedback. However, the effect of metronomes did not reach statistical significance. Conclusions: Feedback devices, particularly audiovisual ones, are associated with improved clinical outcomes in cardiac arrest patients. Their use should be encouraged in both training settings and real-life emergency scenarios to enhance survival rates and ROSC. However, further studies are needed to confirm long-term impacts and to explore the potential benefits of metronomes.

Cardiorespiratory Fitness in Childhood Cancer Survivors: A Systematic Review and Meta-Analysis.

Cardiovascular disease (CVD) is a leading cause of mortality in childhood cancer survivors (CCS) that may be related to the cardiotoxic effects of radiation or chemotherapy and concomitant reductions in cardiorespiratory fitness. Therefore, we sought to compare cardiorespiratory fitness (peak oxygen uptake, V̇O2peak) between CCS and age-matched non-cancer controls (CON). Secondary outcomes included hemodynamics and resting cardiac function. Embase, Scopus, MEDLINE, CINAHL and SPORTDiscus databases were searched from inception to June 2023 for eligible studies. Cross-sectional studies with V̇O2peak measured in CCS and CON were included. Differences in outcomes and pooled estimates for each outcome were estimated from a fixed effects meta-analysis and between group differences were reported as a weighted mean difference (WMD). Of 2026 studies identified, 18 reported V̇O2peak (CCS: n=786, 44% female, mean age: 16-years, time post-therapy: 5.8 years; CON: n=1379, 50% female, mean age: 16-years). V̇O2peak was lower in CCS (WMD: -7.08mL/kg/min, 95% CI: -7.75 to -6.42, I2: 79%, n=2,165) with no difference for peak exercise heart rate (WMD: -1.4bpm, 95% CI: -3.0 to 0.2, I2: 63%, n=741). Resting left-ventricular ejection fraction (WMD: -1.61%, 95% CI: -2.60 to -0.62, I2.: 49%, n=222) and systolic blood pressure were lower (WMD: -3.8mmHg, 95% CI: -5.7 to -1.9, I2: 25%, n=184) while resting heart rate was higher in CCS (WMD: 4.9bpm; 95% CI: 1.8 to 7.9, I2: 55%, n=262). CCS have a marked reduction in cardiorespiratory fitness (7.1ml/kg/min lower than CON) that may have important prognostic implications for their future risk of CVD and mortality.

Mediation-adjusted multivariable Mendelian randomisation study identified novel metabolites related to mental health

BackgroundFrom the pathway perspective, metabolites have the potential to improve knowledge about the aetiology of psychiatric diseases. Previous studies suggested a link between specific blood metabolites and mental disorders, but...

Higher levels of neighborhood deprivation and risk for incident colorectal cancer and mortality outcomes: A systematic review and meta-analysis.

131 Background: Significant geographic and racial disparities exist for colorectal cancer (CRC) incidence and mortality in the United States (US), which may be caused by neighborhood-level deprivation and limited access to preventative cancer screening. We completed the first systematic review and meta-analysis of neighborhood-level deprivation in relation to CRC incidence, mortality, and screening among individuals from the US. Methods: A systematic literature review was completed to identify original research articles from PubMed, Scopus, and Web of Science. Eligible studies reported associations between deprivation at the census block or tract level using a validated deprivation index (e.g. the Area Deprivation Index or Yost Index) and CRC incidence, mortality, or screening outcomes in a US-based sample. A fixed-effects meta-analysis was completed using inverse-variance weighting to estimated hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) for CRC incidence, mortality, and screening outcomes, comparing the highest vs. lowest quantiles of neighborhood-level deprivation. All analyses were completed using the meta package in R. Results: In total, 19 studies were included in the meta-analysis. Living in a neighborhood in the highest quantile of deprivation was associated with significantly higher risk for incident CRC (HR 1.37, 95% CI 1.34-1.41, seven studies). In stratified analysis, positive associations with incident CRC were observed for White (HR 1.43, 95% CI 1.39-1.47, three studies), Black (HR 1.18, 95% CI 0.96-1.44, three studies), and Asian/Pacific Islander individuals (HR 1.18, 95% CI 1.08-1.28, two studies). For individuals diagnosed with CRC, higher deprivation was associated with elevated risk for overall mortality (HR 1.11, 95% CI 1.10-1.13, four studies) and CRC-specific mortality (HR 1.17, 95% CI 1.15-1.19, seven studies). Higher deprivation was associated with lower completion of recommended screening for CRC, including colonoscopy, sigmoidoscopy, or fecal occult blood testing (OR 0.76, 95% CI 0.74-0.79, four studies). Conclusions: Individuals who reside in neighborhoods with high levels of deprivation have significantly elevated risk for CRC incidence and mortality compared to individuals from low deprivation neighborhoods. Targeting healthcare resources to highly deprived neighborhoods to increase uptake of preventative screening may help to address racial and geographic disparities for CRC.

Equal Treatment, Unequal Outcomes? Debunking the Racial Disparity in Renin Angiotensin Aldosterone System Inhibitor Associated Reduction in Heart Failure Hospitalizations

BackgroundRenin angiotensin aldosterone system inhibitors (RAASi) are a mainstay treatment in patients with heart failure with reduced ejection fraction (HFrEF) in part to prevent hospitalizations. However, whether RAAS inhibitors reduce the risk of hospitalization in Black patients is not entirely clear because enrollment of Black patients in previous clinical trials was low, and a previous meta-analysis showed a significant racial disparity: reduction in hospitalizations with an RAAS inhibitor in White patients but not Black patients. Previous studies relied on the use of self-identified race instead of genomic ancestry. Therefore, this study aimed to investigate the role of self-identified race and genomic ancestry in the racial disparity in RAAS inhibitor associated reductions in HFrEF hospitalizations. MethodsThe primary outcome was time to first heart failure hospitalization. A (de-identified) heart failure patient registry and data from the GUIDE-IT multi-center randomized control trial were analyzed with Cox proportional hazards models un/adjusted for clinical risk factors, death as a competing risk, and time-varying RAAS inhibitor exposure. The proportion of Yoruba African ancestry was quantified.. Analysis of self – identified race were performed in both the registry and GUIDE-IT. Analysis of genomic ancestry was only performed in the registry since this information was not available in GUIDE-IT. A fixed effect meta-analysis combined results of both the registry and GUIDE-IT for race. ResultsThe registry had 1010 total HFrEF patients (Black = 509 and White = 501) with 852 having ancestry quantification (>80% Yoruba African Ancestry = 381 and <5% Yoruba African Ancestry = 471). GUIDE-IT had 810 HFrEF patients (Black = 322 and White = 488). There was no significant difference in the association of RAAS inhibitor exposure with heart failure hospitalization by race (meta-analysis p-value for race*RAAS inhibitor exposure interaction = 0.49; Black patients HR [95% CI] for RAAS inhibitor exposure = 0.89 [0.64-1.23)] P = 0.47; White patients = 1.20 (0.83-1.75) P = 0.34). Results were similar when analyzed by ancestry (p-value for ancestry*RAAS inhibitor exposure interaction = 0.57; >80% Yoruba African Ancestry = 0.93 [0.51-1.69] P = 0.80; <5% Yoruba African Ancestry = 1.29 [0.57-2.92] P = 0.54). ConclusionsIn contrast to a previous meta-analysis, this more contemporary analysis of 2 HFrEF patient datasets demonstrates the absence of a racial disparity in RAAS inhibitor associated reductions in heart failure hospitalizations. The difference in this racial disparity over time may be due to improvements in background heart failure therapies, racial differences in healthcare usage, and the use of more advanced statistical approaches.

Searching for a Novel HLA-Cw6-Linked Cardiometabolic Endotype in Psoriatic Disease.

In recent years, a possible connection between HLA-Cw6 and a distinctive cardiometabolic (CM) profile in patients with psoriatic disease (PsD) has been proposed, although there is still little support for this. Our aim was to further investigate this possible association by studying a large population of PsD patients. For this study, three different cohorts of patients with PsD were analyzed: two with a majority of cutaneous psoriasis, pooled n: 600, and a third with only psoriatic arthritis-PsA-cases, n: 340. Potential relationships between HLA-Cw6 and the different CM risk factors (hypertension, diabetes, obesity, dyslipidemia) were analyzed using univariate and multivariate regression models, while the final net effect was assessed using fixed- or random-effects meta-analyses, as appropriate. In the PsA cohort, no association was detected between HLA-Cw6 carriership and any of the CM comorbidity factors. In psoriasis cohorts, after correcting for age, sex, disease duration, and arthritis, HLA-Cw6 carriers had a reduced diabetes risk (OR 0.49, 95%CI: 0.26-0.91, p = 0.026). This latter effect was confirmed by a fixed-effects meta-analysis of the included cohorts (pooled OR: 0.50, 95%CI: 0.27-0.90). This work demonstrates a potential protective effect of the HLA-Cw6 allele on the risk of diabetes in PsD. Our findings together with those of others seem to confirm the existence of a novel HLA-Cw6-linked cardiometabolic endotype in this disease.

Effects of treadmill training combined with transcranial direct current stimulation on mobility, motor performance, balance function, and other brain-related outcomes in stroke survivors: a systematic review and meta-analysis.

Treadmill training (TT) is a gait training technique that has commonly been used in neurorehabilitation, and has positive effects on gait, mobility, and related outcomes in stroke survivors. Transcranial direct current stimulation (tDCS) is a non-invasive approach for modulating brain cortex excitability. To evaluate the available scientific evidence on the effects of TT combined with tDCS on mobility, motor performance, balance function, and brain-related outcomes in stroke survivors. Five databases namely the Cochrane library, PEDro, Web of Science, PubMed, and EMBASE, were searched for relevant studies from inception to March, 2024. Only randomized controlled trials were included, and their methodological quality and risk of bias (ROB) were evaluated using the PEDro scale and Cochrane ROB assessment tool respectively. Qualitative and quantitative syntheses (using fixed effects meta-analysis) were employed to analyze the data. The results revealed that TT combined with active tDCS had significant beneficial effects on some mobility parameters, some gait spatiotemporal parameters, some gait kinematic parameters, gait endurance, gait ability, and corticomotor excitability in stroke survivors, but no significant difference on gait speed (P > 0.05), functional mobility (P > 0.05), motor performance (P > 0.05), or some balance functions (P > 0.05), compared with the control conditions. TT combined with active tDCS significantly improves some gait/mobility outcomes and corticomotor excitability in stroke survivors.

Effects of Global Climate Warming on the Biological Characteristics of Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae).

Spodoptera frugiperda (J.E. Smith) is a significant economic pest that has recently invaded Africa and Asia. However, much of the information regarding its ecological capabilities in these newly invaded environments remains largely unknown. In this study, the life history traits of the fall armyworm under conditions of increased temperature, different photoperiods, and varying humidity levels were systematically evaluated. Among 43 studies, a total of 20 studies were included in the analysis by passing the screening criteria, and random-effects meta-analysis, fixed-effects meta-analysis, and meta-regression were conducted. It has been found that with the increase in temperature above 20 °C, various physiological indicators of the fall armyworm are significantly enhanced. When the temperature reaches 32 °C, the physiological activities of S. frugiperda are at their highest point. As the temperature increases, the duration of each developmental stage of the fall armyworm decreases significantly, accompanied by an increase in oviposition quantity and period in females. Additionally, the pupal development time is shortened, which leads to an increase in the lifespan of the adult moth. Using temperature and relative humidity as environmental variables, the optimal survival conditions for each insect state of the fall armyworm were calculated. These findings can assist in predicting the population dynamics of the fall armyworm and in formulating appropriate and practical management strategies.

The effect of depression and anxiety on survival in patients with glioma: a systematic review and meta-analysis.

Depression and anxiety's impact on glioma patient survival lacks consensus. Understanding these effects can highlight the importance of identifying depression and anxiety in glioma patients, and inform future treatments. This systematic review and meta-analysis aims to clarify the impact of depression and anxiety on glioma patient survival. We conducted a systematic literature search of major databases, including PubMed, Embase, Web of Science Core Collection, Cochrane Library, and PsycINFO, from inception to June 2023, to identify relevant studies. Eligible studies were those that examined the association between depression, anxiety, or both, and survival outcomes in glioma patients. Data were extracted and analyzed using fixed-effects meta-analysis models to calculate pooled hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 15 studies met the inclusion criteria, encompassing a diverse range of glioma patients across different clinical settings and stages. The meta-analysis revealed a statistically significant association between depression and reduced overall survival in glioma patients, with a pooled HR of 1.65 (95% CI: 1.41-1.83, 11 studies). The preliminary univariate meta-regression results indicate no impact of individual study characteristics on the effect size. Likewise, anxiety was associated with worse overall survival, with a pooled HR of 1.65 (95% CI: 1.18-2.31, 5 studies). This meta-analysis underscores the vital need to identify and treat depression and anxiety in glioma patients. Future research should explore the underlying mechanisms, aiding the creation of interventions enhancing both mental health and clinical outcomes for this vulnerable group.

P082 HOW LONG DO BLOOD PRESSURE LOWERING DRUGS TAKE TO WORK? A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIALS

Background: Evidence on the time course of antihypertensive drug (AHTD) efficacy is crucial to guide the frequency of visits recommended in guidelines and when it is appropriate to wait for further effects to accrue. Objective: To assess how quickly AHTD therapy works to lower blood pressure (BP). Methods: We systematically searched multiple electronic databases for relevant randomized, double-blind, placebo-controlled trials of untreated adults. These trials compared fixed doses of AHTDs from the five major classes to a placebo for a minimum of four weeks and reported BP data at baseline, and at least at weeks 2 and 4. Primary outcomes were systolic and diastolic BP reduction at weeks 2, 4, and 8. A fixed-effect meta-analysis was conducted, and a best-fit exponential association model was used to evaluate BP-lowering efficacy over time. Results: A total of 94 trials (25,637 participants) were included. Trial duration ranged from 4-16 (median 8) weeks. The best-fit exponential association model predicted that the reductions in systolic BP (SBP) at weeks 1, 2 and 3 were 64%, 79%, 85% of the reductions seen at week 4. There was no evidence of additional BP reduction after week 4. In absolute terms, after week 2 the additional reduction in BP averaged only 1.8/0.8 mmHg by week 4 and 0.4/0.2 mmHg between week 4 and week 8. This finding was consistent across trials by drug class, with no evidence that renin-angiotensin-aldosterone system inhibitors, diuretics, beta-blockers, calcium channel blockers, diuretics or combinations took longer to work. Baseline BP did appear to modify the effect, but still there was no additional benefit after 4 weeks. Conclusion: BP lowering drugs work quickly, with little additional BP lowering occurring after 2 weeks. These findings have relevance for guidelines and for addressing treatment inertia related to expectation of time needed for drugs to work fully.