Risk Ratio For All-cause Mortality Research Articles

Effect of Dapagliflozin in Patients with Heart Failure: A Systematic Review and Meta-Analysis.

Heart failure (HF) is a major cause of recurrent hospitalization and death worldwide. Sodium-glucose cotransporter-2 inhibitors including dapagliflozin are anti-diabetic drugs with promising cardiovascular (CV) effects. We performed systematic review and meta-analysis of randomized controlled trials investigating the effects of dapagliflozin in heart failure patients. We searched PubMed, Scopus and ScienceDirect databases. A total of 1,567 studies from January 2017 to September 10, 2022, were screened. After applying exclusion criteria, 22 studies were retrieved for full-text screening, and nine of them were eligible for this meta-analysis. Effect estimates for dichotomous variables were expressed as risk ratio (RR) and 95% CI. The primary outcomes were the incidence of all-cause mortality, hospitalization due to HF, and CV death. This review was registered on PROSPERO with ID CRD42022347793. A total of 14,032 patients were included. The overall risk ratio of all-cause mortality favored the dapagliflozin group over the placebo/standard therapy group (RR = 0.89, 95% CI: 0.82-0.97, P = 0.006) and the pooled studies were not heterogenous (I2 = 0%). Additionally, dapagliflozin significantly reduced the hospitalization due to heart failure (RR = 0.76, 95% CI: 0.70-0.84, P > 0.00001, I2 = 0%), cardiovascular death (RR = 0.87, 95% CI: 0.78-0.97, P = 0.01, I2 = 0%) and their composite outcomes. Dapagliflozin reduces the risk of all-cause mortality, heart failure hospitalizations and cardiovascular death in a wide range of heart failure patients.

Association between the beta-blockers, calcium channel blockers, all-cause mortality and length of hospitalization in patients with heart failure with preserved ejection fraction: A meta-analysis of randomized controlled trials.

To establish an association between beta-blockers (BBs), calcium channel blockers (CCBs), all-cause mortality, and hospitalization in patients with Heart failure with preserved Ejection Fraction (HFpEF). The present meta-analysis has been performed as per the guidelines of (PRISMA). An inclusive literature search was made without any limitations on language using the electronic databases Cochrane Library, EMBASE, and PubMed up to November 2022. The outcomes evaluated in this meta-analysis involved all-cause mortality and hospitalization due to heart failure. The number of patients with HFpEF and their positive outcomes was extracted and analyzed using RevMan software. In total, 10 articles were included in the present meta-analysis, with a pooled sample size of 12 940 HFpEF patients. In comparison with placebo, both BB and CCB substantially reduced the risk of all-cause mortality and hospitalization. However, BB are more effective because they provide a significant reduction in all-cause mortality (risk ratio (RR) = 0.60; 95% confidence interval [CI] = 0.43-0.83; p = .002] and hospitalization (RR = 0.54; 95% CI = 0.37-0.80; p = .002) as compared with CCB with a risk ratio of all-cause mortality (RR = 0.77; 95% CI = 0.60-0.98; p = .03) and hospitalization (RR = 0.63; 95% CI = 0.44-0.90; p < .00001). A random-effects model was used because of high heterogeneity between the studies (I2 > 70%). The current meta-analysis suggests that BBs were more beneficial than CCB in reducing all-cause mortality and hospitalization duration in patients with HFpEF.

Diabetes Mellitus and Tuberculosis Treatment Outcomes: Interaction Assessment Between Hyperglycemia and Human Immunodeficiency Virus in the State of Georgia, 2015-2020.

Diabetes mellitus and human immunodeficiency virus (HIV) are independent risk factors for poor outcomes among people with tuberculosis (TB). To date, information on the joint impact of diabetes and HIV on TB outcomes is limited. We aimed to estimate (1) the association between hyperglycemia and mortality and (2) the effect of joint exposure to diabetes and HIV on mortality. We conducted a retrospective cohort study among people with TB in the state of Georgia between 2015 and 2020. Eligible participants were 16 or older, did not have a previous TB diagnosis, and were microbiologically confirmed or clinical cases. Participants were followed during TB treatment. Robust Poisson regression was used to estimate risk ratios for all-cause mortality. Interaction between diabetes and HIV was assessed on the additive scale using the attributable proportion and on the multiplicative scale with product terms in regression models. Of 1109 participants, 318 (28.7%) had diabetes, 92 (8.3%) were HIV positive, and 15 (1.4%) had diabetes and HIV. Overall, 9.8% died during TB treatment. Diabetes was associated with an increased risk of death among people with TB (adjusted risk ratio [aRR] = 2.59; 95% confidence interval [CI], 1.62-4.13). We estimated that 26% (95% CI, -43.4% to 95.0%) of deaths among participants with diabetes mellitus and HIV were due to biologic interaction. Diabetes alone and co-occurring diabetes and HIV were associated with an increased risk of all-cause mortality during TB treatment. These data suggest a potential synergistic effect between diabetes and HIV.

Socioeconomic deprivation and prognostic outcomes in acute coronary syndrome: A meta-analysis using multidimensional socioeconomic status indices

BackgroundLow socioeconomic status (SES) is an important prognosticator amongst patients with acute coronary syndrome (ACS). This paper analysed the effects of SES on ACS outcomes. MethodsMedline and Embase were searched for articles reporting outcomes of ACS patients stratified by SES using a multidimensional index, comprising at least 2 of the following components: Income, Education and Employment. A comparative meta-analysis was conducted using random-effects models to estimate the risk ratio of all-cause mortality in low SES vs high SES populations, stratified according to geographical region, study year, follow-up duration and SES index. ResultsA total of 29 studies comprising of 301,340 individuals were included, of whom 43.7% were classified as low SES. While patients of both SES groups had similar cardiovascular risk profiles, ACS patients of low SES had significantly higher risk of all-cause mortality (adjusted HR:1.19, 95%CI: 1.10–1.1.29, p < 0.001) compared to patients of high SES, with higher 1-year mortality (RR:1.08, 95%CI:1.03–1.13, p = 0.0057) but not 30-day mortality (RR:1.07, 95%CI:0.98–1.16, p = 0.1003). Despite having similar rates of ST-elevation myocardial infarction and non-ST-elevation ACS, individuals with low SES had lower rates of coronary revascularisation (RR:0.95, 95%CI:0.91–0.99, p = 0.0115) and had higher cerebrovascular accident risk (RR:1.25, 95%CI:1.01–1.55, p = 0.0469). Excess mortality risk was independent of region (p = 0.2636), study year (p = 0.7271) and duration of follow-up (p = 0.0604) but was dependent on the SES index used (p < 0.0001). ConclusionLow SES is associated with increased mortality post-ACS, with suboptimal coronary revascularisation rates compared to those of high SES. Concerted efforts are needed to address the global ACS-related socioeconomic inequity. Registration and protocolThe current study was registered with PROSPERO, ID: CRD42022347987.

Long-Term Outcomes of Perioperative Versus Nonoperative Myocardial Infarction: A Danish Population-Based Cohort Study (2000-2016).

Perioperative myocardial infarction is a serious cardiovascular complication of noncardiac surgery. The clinical course of perioperative myocardial infarction, other than all-cause mortality, is largely unknown. We examined long-term fatal and nonfatal outcomes of perioperative myocardial infarction compared with nonoperative myocardial infarction. We conducted a population-based cohort study of first-time myocardial infarction in Denmark from 2000 to 2016. We calculated cumulative incidence of all-cause mortality, cardiac mortality, recurrent myocardial infarction, heart failure, stroke, venous thromboembolism, acute kidney injury, and kidney failure with replacement therapy. We computed 5-year risk ratios adjusted for age, sex, year of diagnosis, educational level, and comorbidities. We identified 5068 patients with perioperative myocardial infarction and 137 862 patients with nonoperative myocardial infarction. The 5-year risk of all-cause mortality was 67.5% (95% CI, 66.1%-69.0%) for perioperative myocardial infarction patients and 38.0% (95% CI, 37.7%-38.3%) for nonoperative myocardial infarction patients. The adjusted risk ratio of all-cause mortality was 1.13 (95% CI, 1.11-1.16) at 5 years. After adjustment, we found no association between patients with perioperative myocardial infarction and 5-year cardiac mortality, recurrent myocardial infarction, heart failure, stroke, or kidney failure with replacement therapy when compared with nonoperative myocardial infarction patients. Perioperative myocardial infarction patients had a higher relative risk of venous thromboembolism (5-year risk ratio, 1.21 [95% CI, 1.01-1.46]) and acute kidney injury (5-year risk ratio, 1.37 [95% CI, 1.22-1.53]). Compared with nonoperative myocardial infarction patients, perioperative myocardial infarction patients had elevated risk of all-cause mortality, venous thromboembolism, and acute kidney failure. In addition to the myocardial infarction component of perioperative myocardial infarction, this poor prognosis seemed associated with the surgery or underlying comorbidities. These findings warrant further research on strategies to reduce the risk of perioperative myocardial infarction and on strategies to manage perioperative myocardial infarction.

Timing of adjuvant chemotherapy initiation and mortality among colon cancer patients at a safety-net health system

BackgroundPrior studies reported survival benefits from early initiation of adjuvant chemotherapy for stage III colon cancer, but this evidence was derived from studies that may be sensitive to time-related biases. Therefore, we aimed to estimate the effect of initiating adjuvant chemotherapy ≤8 or ≤ 12 weeks on overall and disease-free survival among stage III colon cancer patients using a study design that helps address time-related biases.MethodsWe used institutional registry data from JPS Oncology and Infusion Center, a Comprehensive Community Cancer Program. Eligible patients were adults aged < 80 years, diagnosed with first primary stage III colon cancer between 2011 and 2017, and received surgical resection with curative intent. We emulated a target trial with sequential eligibility. We subsequently pooled the trials and estimated risk ratios (RRs) along with 95% confidence limits (CL) for all-cause mortality and recurrence or death at 5-years between initiators and non-initiators of adjuvant chemotherapy ≤8 or ≤ 12 weeks using pseudo-observations and a marginal structural model with stabilized inverse probability of treatment weights.ResultsOur study population comprised 222 (for assessing initiation ≤8 weeks) and 310 (for assessing initiation ≤12 weeks) observations, of whom the majority were racial/ethnic minorities (64–65%), or uninsured with or without enrollment in our hospital-based medical assistance program (68–71%). Initiation of adjuvant chemotherapy ≤8 weeks of surgical resection did not improve overall survival (RR for all-cause mortality = 1.04, 95% CL: 0.57, 1.92) or disease-free survival (RR for recurrence or death = 1.07, 95% CL: 0.61, 1.88). The results were similar for initiation of adjuvant chemotherapy ≤12 weeks of surgical resection.ConclusionsOur results suggest that the overall and disease-free survival benefits of initiating adjuvant chemotherapy ≤8 or ≤ 12 weeks of surgical resection may be overestimated in prior studies, which may be attributable to time-related biases. Nevertheless, our estimates were imprecise and differences in population characteristics are an alternate explanation. Additional studies that address time-related biases are needed to clarify our findings.

Mortality in people with schizophrenia: a systematic review and meta-analysis of relative risk and aggravating or attenuating factors.

People with schizophrenia die 15-20 years prematurely. Understanding mortality risk and aggravating/attenuating factors is essential to reduce this gap. We conducted a systematic review and random-effects meta-analysis of prospective and retrospective, nationwide and targeted cohort studies assessing mortality risk in people with schizophrenia versus the general population or groups matched for physical comorbidities or groups with different psychiatric disorders, also assessing moderators. Primary outcome was all-cause mortality risk ratio (RR); key secondary outcomes were mortality due to suicide and natural causes. Other secondary outcomes included any other specific-cause mortality. Publication bias, subgroup and meta-regression analyses, and quality assessment (Newcastle-Ottawa Scale) were conducted. Across 135 studies spanning from 1957 to 2021 (schizophrenia: N=4,536,447; general population controls: N=1,115,600,059; other psychiatric illness controls: N=3,827,955), all-cause mortality was increased in people with schizophrenia versus any non-schizophrenia control group (RR=2.52, 95% CI: 2.38-2.68, n=79), with the largest risk in first-episode (RR=7.43, 95% CI: 4.02-13.75, n=2) and incident (i.e., earlier-phase) schizophrenia (RR=3.52, 95% CI: 3.09-4.00, n=7) versus the general population. Specific-cause mortality was highest for suicide or injury-poisoning or undetermined non-natural cause (RR=9.76-8.42), followed by pneumonia among natural causes (RR=7.00, 95% CI: 6.79-7.23), decreasing through infectious or endocrine or respiratory or urogenital or diabetes causes (RR=3 to 4), to alcohol or gastrointestinal or renal or nervous system or cardio-cerebrovascular or all natural causes (RR=2 to 3), and liver or cerebrovascular, or breast or colon or pancreas or any cancer causes (RR=1.33 to 1.96). All-cause mortality increased slightly but significantly with median study year (beta=0.0009, 95% CI: 0.001-0.02, p=0.02). Individuals with schizophrenia <40 years of age had increased all-cause and suicide-related mortality compared to those ≥40 years old, and a higher percentage of females increased suicide-related mortality risk in incident schizophrenia samples. All-cause mortality was higher in incident than prevalent schizophrenia (RR=3.52 vs. 2.86, p=0.009). Comorbid substance use disorder increased all-cause mortality (RR=1.62, 95% CI: 1.47-1.80, n=3). Antipsychotics were protective against all-cause mortality versus no antipsychotic use (RR=0.71, 95% CI: 0.59-0.84, n=11), with largest effects for second-generation long-acting injectable anti-psychotics (SGA-LAIs) (RR=0.39, 95% CI: 0.27-0.56, n=3), clozapine (RR=0.43, 95% CI: 0.34-0.55, n=3), any LAI (RR=0.47, 95% CI: 0.39-0.58, n=2), and any SGA (RR=0.53, 95% CI: 0.44-0.63, n=4). Antipsychotics were also protective against natural cause-related mortality, yet first-generation antipsychotics (FGAs) were associated with increased mortality due to suicide and natural cause in incident schizophrenia. Higher study quality and number of variables used to adjust the analyses moderated larger natural-cause mortality risk, and more recent study year moderated larger protective effects of antipsychotics. These results indicate that the excess mortality in schizophrenia is associated with several modifiable factors. Targeting comorbid substance abuse, long-term maintenance antipsychotic treatment and appropriate/earlier use of SGA-LAIs and clozapine could reduce this mortality gap.

A cost-effectiveness and value of information analysis to inform future research of tranexamic acid for older adults experiencing mild traumatic brain injury

BackgroundTranexamic acid reduces head injury deaths in patients with CT scan evidence of intracranial bleeding after mild traumatic brain injury (TBI). However, the cost-effectiveness of tranexamic acid for people with mild TBI in the pre-hospital setting, prior to CT scanning, is uncertain. A large randomised controlled trial (CRASH-4) is planned to address this issue, but the economic justification for it has not been established. The aim of the analysis was to estimate the likelihood of tranexamic acid being cost-effective given current evidence, the treatment effects required for cost-effectiveness, and the expected value of performing further research.MethodsAn early economic decision model compared usual care for mild TBI with and without tranexamic acid, for adults aged 70 and above. The evaluation was performed from a UK healthcare perspective over a lifetime time horizon, with costs reported in 2020 pounds (GBP) and outcomes reported as quality-adjusted life years (QALYs). All analyses used a £20,000 per QALY cost-effectiveness threshold.ResultsIn the base case analysis, tranexamic acid was associated with an incremental cost-effectiveness ratio of £4885 per QALY gained, but the likelihood of it being cost-effective was highly dependent on the all-cause mortality treatment effect. The value of perfect information was £22.4 million, and the value of perfect information for parameters that could be collected in a trial was £21.9 million. The all-cause mortality risk ratio for tranexamic acid and the functional outcomes following TBI had the most impact on cost-effectiveness.ConclusionsThere is a high degree of uncertainty in the cost-effectiveness of tranexamic acid for older adults experiencing mild TBI, meaning there is a high value of performing future research in the UK. The value in a global context is likely to be far higher.

Effects of Influenza Vaccination in Patients with Interstitial Lung Diseases: An Epidemiological Claims Data Analysis

RationaleVaccination is the most effective protection against influenza. Patients with interstitial lung diseases (ILDs) represent a high-risk group for influenza complications. Thus, yearly influenza vaccination is recommended, but evidence on its effects is sparse.ObjectivesThis study aimed to compare all-cause mortality and all-cause and respiratory-related hospitalization between vaccinated and unvaccinated patients with ILD.MethodsUsing data from the largest German statutory health insurance fund (about 27 million insurees in 2020), we analyzed four influenza seasons from 2014–2015 to 2017–2018 and compared vaccinated with unvaccinated patients with ILD. Starting from September 1 of each year, we matched vaccinated and unvaccinated patients in a 1:1 ratio using a rolling cohort design. Mortality and hospitalization were compared with Kaplan-Meier plots, and effects were calculated during the influenza season (in season) with risk ratios.ResultsBoth the vaccinated and the unvaccinated cohorts included 7,503 patients in 2014–2015, 10,318 in 2015–2016, 12,723 in 2016–2017, and 13,927 in 2017–2018. Vaccination rates were low at 43.2% in season 2014–2015 and decreased over time to 39.9% in season 2017–2018. The risk ratios for all-cause mortality were 0.79 (95% confidence interval [CI], 0.65–0.97; P = 0.02) in season 2014–2015, 0.66 (95% CI, 0.54–0.80; P < 0.001) in 2015–2016, 0.89 (95% CI, 0.76–1.04; P = 0.15) in 2016–2017, and 0.95 (95% CI, 0.81–1.12; P = 0.57) in 2017–2018. The effects on all-cause hospitalization and respiratory-related hospitalization were similar in all seasons.ConclusionsAlthough an unequivocally beneficial impact of influenza vaccination in patients with ILD could not be demonstrated, we observed promising results regarding avoidance of all-cause mortality in half of the seasons observed. Given the low vaccination rates, further efforts are necessary to improve vaccination rates in patients with ILD.

Cardiovascular safety of celecoxib in rheumatoid arthritis and osteoarthritis patients: A systematic review and meta-analysis.

To assess the cardiovascular safety of celecoxib compared to non-selective non-steroid anti-inflammatory drugs or placebo. We included randomized controlled trials of oral celecoxib compared with a non-selective NSAID or placebo in rheumatoid arthritis and osteoarthritis patients. We conducted searches in EMBASE, Cochrane CENTRAL, MEDLINE, China National Knowledge Infrastructure, VIP, Wanfang, and Chinese Biomedical Literature Database. Study selection and data extraction were done by two authors independently. The risk of bias was assessed using Cochrane's risk-of-bias Tool for Randomized Trials. The effect size was presented as a risk ratio with their 95% confidence interval. Until July 22nd, 2021, our search identified 6279 records from which, after exclusions, 21 trials were included in the meta-analysis. The overall pooled risk ratio for Antiplatelet Trialists Collaboration cardiovascular events for celecoxib compared with any non-selective non-steroid anti-inflammatory drugs was 0.89 (95% confidence interval: 0.80-1.00). The pooled risk ratio for all-cause mortality for celecoxib compared with non-selective non-steroid anti-inflammatory drugs was 0.81 (95% confidence interval: 0.66-0.98). The cardiovascular mortality rate of celecoxib was lower than non-selective non-steroid anti-inflammatory drugs (risk ratio: 0.75, 95% confidence interval: 0.57-0.99). There was no significant difference between celecoxib and non-selective non-steroid anti-inflammatory drugs or placebo in the risk of other cardiovascular events. Celecoxib is relatively safe in rheumatoid arthritis and osteoarthritis patients, independent of dose or duration. But it remains uncertain whether this would remain the same in patients treated with aspirin and patients with established cardiovascular diseases.

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials

BackgroundConvalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX).MethodsIn this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung–Knapp–Sidik–Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence.ResultsA total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis.ConclusionsConvalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.

The impact of non-pharmacological therapies on cardiovascular outcomes in patients with refractory angina: a systematic review and meta-analysis of randomized controlled trials

Abstract Despite advances in revascularization techniques and optimal medical management, refractory angina (RFA) represents an essential group of patients where progress has stalled, and in which therapeutic approaches remain uncertain. Numerous randomized control trials have reported clinical outcomes on a variety of treatments but to date no direct outcome comparison has been made. Our aim is to investigate and compare the outcomes of these different non-pharmacological technologies in RFA, centring on major adverse cardiac events and all-cause mortality. We performed a systematic review and meta-analysis of randomized controlled trials using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A comprehensive search was performed of PubMed, EMBASE (Excerpta Medica database),Cochrane, ClinicalTrials.gov, Google Scholar databases of randomized controlled trials, and scientific session abstracts. Studies were deemed eligible if they met the following criteria: (1) full-length publications in peer-reviewed journals; (2) evaluated non-pharmacological therapies use in patients with no further revascularization options while on optimal medical treatment; (3) patients had ongoing angina, Canadian Cardiovascular Society class II–IV; and (4) included a placebo/control arm. We calculated risk ratios for all-cause mortality, combined MACE events. We assessed heterogeneity using χ2 and I2 tests. We analysed 3292 citations with 51 randomized control trials testing 9 therapies including angiogenic proteins, stem-cell therapy, lipoprotein apheresis, coronary sinus reducer, spinal cord stimulator, percutaneous laser revascularization, shock-wave therapy, transmyocardial laser revascularization and enhanced external counter pulsation all meeting the inclusion criteria (table 1). Our analysis identified stem cell therapy as the only therapy with a reduction in all-cause mortality (Odds ratio, 0.45; CI, 0.21–1.00) (figure 1). A corresponding reduction in major adverse cardiac events (MACE) was also seen with stem cell therapy (OR 0.48: CI 0.30–0.75) alongside patients who received angiogenic proteins (OR 0.72: CI 0.55–0.93) and cardiac shockwave therapy (OR, 0.21: CI 0.10–0.46) Improvements in secondary measures of angina symptoms or frequency were seen with stem cell therapy, angiogenic proteins, coronary sinus reducer, spinal cord stimulator, shock-wave therapy, transmyocardial laser revascularization and enhanced external counterpulsation. This is the largest meta-analysis comparing outcomes of novel technologies used in refractory angina. This suggests that stem cell therapy is the only non-pharmacological therapy for RFA associated with a reduction in mortality, MACE and anginal symptoms. We propose further larger randomized control trials, to support these findings. Funding Acknowledgement Type of funding sources: None. Table 1. Randomized control trials and outcomesFigure 1. All-cause mortality forest plot

Restrictive vs liberal blood transfusion strategy in patients with symptomatic coronary artery disease: meta-analysis from randomized controlled trials

Abstract Background Anemia is common in patients with symptomatic coronary artery disease. Observational studies investigated blood transfusion threshold in symptomatic coronary artery disease but results were conflicting. Meta-analyses evaluating transfusion threshold utilized data mainly from observational trials but no meta-analysis, to our knowledge, used data solely from randomized clinical trials. Objective The goal of our study is to evaluate efficacy and safety outcomes in anemic patients presenting with symptomatic coronary artery disease using pooled data from randomized clinical trials. Methods We queried Medline, Embase and Cochrane data bases for randomized clinical trials comparing restrictive blood transfusion (defined as transfusion when hemoglobin is less than 8 gm/dl) vs liberal blood transfusion (transfusion when hemoglobin is less than 10 gm/dl) in patients presenting with symptomatic artery disease or acute coronary syndrome. We identified 3 randomized controlled trials; MINT, CRIT and REALITY trials. Data were pooled from 3 trials. Efficacy outcomes evaluated were all-cause mortality and New or recurrent myocardial infarction. Safety outcomes were congestive heart failure at 30-day follow up. Results A total of 820 patients were included in our meta-analysis; 420 patients in restrictive blood transfusion protocol and 400 in liberal blood transfusion protocol There was no difference between two groups at 30-day follow up in all identified outcomes (all-cause mortality, new or recurrent myocardial infarction, and Congestive heart failure). 55 patients died (22/420 in restrictive group and 33/400 in liberal group). Risk ratio of all-cause mortality in restrictive group was 0.63 [95% CI (0.38–1.07), P=0.09, I2=30%]. 15/420 in restrictive group and 16/400 in liberal group had new or recurrent myocardial infarction. Risk ratio of myocardial infarction in restrictive group was 0.91 [95% CI (0.46–1.80), P=0.78, I2=0%]. 20/420 patients in restrictive group and 24/400 in liberal group had congestive heart failure with risk ratio of 0.80 [95% CI (0.19–3.37), P=0.30, I2=76%] in restrictive group. Conclusion Our meta-analysis showed similar outcomes between restrictive and liberal transfusion policies in patients presenting with symptomatic coronary artery disease of acute myocardial infarction. Our findings are consistent with available data about restricting transfusion in general population. Restricting blood transfusion might be cost-effective. Further studies are warranted to evaluate long term safety and efficacy of such approach. Funding Acknowledgement Type of funding sources: None.

Rhythm control in patients with atrial fibrillation and heart failure: a meta-analysis of randomized controlled trials

Abstract Background Atrial fibrillation (AF) is a common arrhythmia that can promote or worsen heart failure (HF). Limited data exist to guide treatment for patients with AF with HF regarding rate versus rhythm control. Purpose To perform a meta-analysis of randomized controlled trials (RCT) in the determination of the efficacy of rhythm control as compared to rate control among patients with AF and HF. Methods Extensive search of PubMed, Cochrane Library, Ovid, EMBASE, Google scholar, and Medline was done up to October 2020. Studies were limited to RCTs comparing rhythm control in patients with atrial fibrillation and heart failure with rate control. Outcome measures include all-cause mortality and cardiovascular mortality. Statistical analysis was done using Review manager V5.3. Results A total of 9800 patients were included in the pooled analysis of the comparison of rhythm control versus rate control strategy in patients with AF and HF. All pooled analyses were done using random effects model. The pooled risk ratio for all-cause mortality of rate control vs rhythm control did not achieve significance at 1.15, with 95% CI 0.91 to 1.45, and p=0.24. There was statistically significant heterogeneity across the two studies with I2 of 54% and p=0.02 (Figure 1A). The pooled risk ratio for cardiovascular mortality in rate control strategy vs rhythm control is 1.19, with 95% CI 0.94 to 1.50, and p=0.15 (Figure 1B). Eight trials with 9987 participants reported stroke. The pooled risk ratio of stroke in rate control vs rhythm control is 1.11, with 95% CI 0.84 to 1.46, and p=0.47 (Figure 1C). The 95% CI for the pooled risk ratio cross 1.00, indicating an equivocal result. Our results do not indicate statistical heterogeneity across the studies with I2 of 28% and p=0.27. Seven trials with 8311 participants reported bleeding. The pooled risk ratio of hospitalization for bleeding in rate control vs rhythm control is 1.18, with 95% CI 0.81 to 1.73, and p=0.39 (Figure 1D). Thus, we have insufficient evidence to demonstrate whether rate or rhythm control have significantly higher or lower risk for bleeding. Four trials with 8468 participants reported hospitalization rate. The pooled risk ratio of hospitalization in rate control compared to rhythm control is 0.96, with 95% CI 0.86 to 1.07, and p=0.42 (Figure 1E). None of the studies individually showed statistically significant differences but AF–CHF showed benefit of rate control in the first year after enrolment (p=0.001) and a tendency favouring rate control (p=0.06) when the study was analysed in full length except for AF-CHF. Conclusion Among patients with AF and concomitant HF, there is no sufficient evidence between rate and rhythm control strategies in their effects to rates of mortality and major clinical outcomes; therefore, choosing an appropriate therapeutic strategy should consider individual variations such as patient preferences, comorbidities, and treatment cost. Funding Acknowledgement Type of funding sources: None. Forest Plot A–CForest Plot D–E

Hypomagnesemia Is a Risk Factor for Cardiovascular Disease- and Noncardiovascular Disease-Related Mortality in Peritoneal Dialysis Patients

Purpose: Recent research has shown that hypomagnesemia is associated with increased all-cause mortality in hemodialysis patients. However, the relationship between the long-term prognosis of peritoneal dialysis (PD) and the study is not yet clear. This study will analyze the effects of hypomagnesemia on all-cause, cardiovascular diseases (CVD), and non-CVD mortality in PD patients. Method: In a retrospective cohort study, 1,004 samples were selected from 7 PD centers in China. Based on the baseline blood magnesium level at the beginning of stable dialysis, all patients were classified into blood magnesium <0.7 mmol/L group, 0.7–1.2 mmol/L group, and >1.2 mmol/L group (the end event was death). The Kaplan-Meier method was used to calculate the difference in cumulative survival rate; the Cox proportional hazard model was used to analyze the risk factors of all-cause, CVD, and non-CVD death causes. Results: Cox multiple regression analysis results (reference comparison of 0.7–1.2 mmol/L group): patients with serum magnesium <0.7 mmol/L have a higher risk ratio of all-cause mortality (HR = 1.580, 95% CI: 1.222–2.042, p = 0.001), and it is also obvious after correction by multiple models (HR = 1.578, 95% CI: 1.196–2.083, p = 0.001). Subgroup analysis of the causes of death was as follows: CVD risk (HR = 1.628, 95% CI: 1.114–2.379, p = 0.012) and non-CVD risk (HR = 1.521, 95% CI: 1.011–2.288, p = 0.044). Further analysis of the causes of infection-related death in non-CVD is also significant (HR = 1.919, 95% CI: 1.131–3.1257, p = 0.016). On the other hand, the serum magnesium>1.2 mmol/L group had lower all-cause mortality after correction (HR = 0.687, 95% CI: 0.480–0.985, p = 0.041), and subgroup analysis of the cause of death had no statistical significance (p > 0.05). Conclusions: Hypomagnesemia (serum magnesium <0.7 mmol/L) during stable dialysis in PD patients is a risk factor for CVD- and non-CVD-related mortality, especially infection-related death causes.

Changes over 15\u2009years in the contribution of adiposity and smoking to deaths in England and Scotland

BackgroundFor many years smoking has been the major threat to public health in developed countries. However, smoking prevalence has declined over a period when adiposity has increased. The aim of this study was to determine whether adiposity now accounts for more deaths than smoking in the general population as a whole or sub-groups of it.MethodsThis is a comparative risk assessment study using Health Surveys for England and Scottish Health Surveys from 2003 to 2017. Annual prevalence of overweight, obesity, current and former smoking were obtained and combined using population-based weights. Sex-specific risk ratios for all-cause mortality were obtained from the most recently published meta-analyses. Population attributable fractions across yeas were then estimated.FindingsOverall, deaths attributable to current/former smoking declined from 23.1% (95% CI 20.6–25.8%) in 2003 to 19.4% (95% CI 17.3–21.6%) in 2017, whilst those attributable to adiposity (overweight or obesity) increased from 17.9% (95% CI 17.3–18.4%) in 2003 to 23.1% (95% CI 22.3–23.8%) in 2017 with cross-over occurring in 2013. Cross-over occurred earlier in men (2011) than women (2014). It occurred in 2006 for those aged over 65 years of age and in 2012 for those aged 45–64 years. Below 45 years, smoking remained the larger contributor to mortality.InterpretationAdiposity now accounts for more deaths in England and Scotland than smoking among people in middle- and old-age. National strategies to address adiposity should be a public health priority.

Health insurance status and outcomes in children, adolescents, and young adults: a systematic review and meta-analysis.

The impacts of health insurance status on survival outcomes in children, adolescents, and young adults (aged 0-39 years) with malignant tumors have not been addressed in depth. The present study aimed to identify significant relationships of health insurance condition with overall survival or all-cause mortality among children (age 0-14 years) and adolescents and young adults (AYAs, age 15-39 years) with malignant tumors. PubMed, Wiley Cochrane Central Register of Controlled Trials, Econlit, CINAHL, Web of Knowledge, PsychInfo, Business Source Premier, ProQuest Dissertation & Theses Database, and SCOPUS were systematically searched from inception to February 29, 2020 with no language restriction. All related articles comparing the effect of health insurance status on the risk of overall survival and the risk of all-cause mortality in malignant conditions affecting children and AYAs were identified. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were computed using a random- or fixed-effect model as per the heterogeneity evaluated using Cochran`s Q and I < sup > 2 < /sup > statistics. Fourteen studies including 149,680 individuals were selected for this meta-analysis. The pooled RR for all-cause mortality with insurance versus without insurance was 0.78 (95%CI, 0.71-0.86; I2=33.7%). Among the insurance types, patients with private insurance presented with a lower all-cause mortality (RR 0.70, 95% CI 0.60-0.82), with considerable heterogeneity (I2=83.3%). The findings of this review suggest that a lack of or insufficient insurance is related to all-cause mortality of AYAs with malignant cancers. Strategies aimed at identifying causality and reducing disparities are warranted.

Does the Impact of Frailty on All-Cause Mortality in Older Persons Differ Between Women and Men? A Meta-Analysis

ObjectiveSex-specific impact of frailty on all-cause mortality in older age population remains controversial. This meta-analysis aimed to evaluate the association between frailty and all-cause mortality in older age women vs men from the general population. DesignMeta-analysis. Setting and ParticipantsPubMed and Embase databases were searched until March 25, 2020 for studies reporting sex-specific association of frailty phenotype or index with all-cause mortality among the older general population (age ≥60 years) in the same study. MeasurementsAll-cause mortality for the frail vs robust individuals. ResultsEight studies enrolling a total of 87, 000 individuals were identified. Using the frailty phenotype, the pooled risk ratio of all-cause mortality was 2.41 [95% confidence interval (CI) 2.07–2.80] for frail women and 2.94 (95% CI 2.12–4.09) for frail men. Using the frailty index, the pooled risk ratio of all-cause mortality was 3.23 (95% CI 2.16–4.83) for frail women and 2.63 (95% CI 2.33–2.98) for frail men. The pooled female-to-male ratio of relative risks was 0.93 (95% CI 0.76–1.13) for the frailty phenotype and 1.22 (95% CI 0.79–1.88) for the frailty index. Conclusions and ImplicationsOlder men and women with frailty confer a higher risk of all-cause mortality in the general population from the same source. However, there is no significant sex difference in the association between phenotype or index and all-cause mortality.

D-dimer levels on admission and all-cause mortality risk in COVID-19 patients: a meta-analysis.

D-dimer level on admission is a promising biomarker to predict mortality in patients with COVID-19. In this study, we reviewed the association between on-admission D-dimer levels and all-cause mortality risk in COVID-19 patients. Peer-reviewed studies and preprints reporting categorised D-dimer levels on admission and all-cause mortality until 24 May 2020 were searched for using the following keywords: 'COVID-19', 'D-dimer' and 'Mortality'. A meta-analysis was performed to determine the pooled risk ratio (RR) for all-cause mortality. In total, 2911 COVID-19 patients from nine studies were included in this meta-analysis. Regardless of the different D-dimer cut-off values used, the pooled RR for all-cause mortality in patients with elevated vs. normal on-admission D-dimer level was 4.77 (95% confidence interval (CI) 3.02-7.54). Sensitivity analysis did not significantly affect the overall mortality risk. Analysis restricted to studies with 0.5 μg/ml as the cut-off value resulted in a pooled RR for mortality of 4.60 (95% CI 2.72-7.79). Subgroup analysis showed that the pooled all-cause mortality risk was higher in Chinese vs. non-Chinese studies (RR 5.87; 95% CI 2.67-12.89 and RR 3.35; 95% CI 1.66-6.73; P = 0.29). On-admission D-dimer levels showed a promising prognostic role in predicting all-cause mortality in COVID-19 patients, elevated D-dimer levels were associated with increased risk of mortality.

Variation of effect estimates in the analysis of mortality and length of hospital stay in patients with infections caused by bacteria-producing extended-spectrum beta-lactamases: a systematic review and meta-analysis

ObjectiveTo assess the variation of effect estimates in the analysis of mortality and length of stay (LOS) in patients with infections caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae.DesignSystematic review and meta-analysisMethodsLiterature...