Effectiveness of Single Versus Multiple Inhaler Triple Therapy on Mortality and Cardiopulmonary Risk Reduction in COPD: The SKOPOS-MAZI Study.

Background: Patients with chronic obstructive pulmonary disease (COPD) have elevated cardiopulmonary and mortality risk, particularly following exacerbations. While single inhaler triple therapies (SITTs), such as budesonide/glycopyrrolate/formoterol fumarate (BGF), reduce cardiopulmonary risk versus dual bronchodilator therapy, there is limited evidence comparing outcomes with SITTs versus multiple inhaler triple therapies (MITTs).

Methods: SKOPOS-MAZI was a retrospective comparative effectiveness study in patients with COPD aged ≥40 years using US administrative claims data from Optum's deidentified Clinformatics® Data Mart Database.

Increased Risk of Severe Cardiovascular Events Following Exacerbations of Chronic Obstructive Pulmonary Disease: Results of the EXACOS-CV Study in Japan.

Introduction: Severe exacerbations of chronic obstructive pulmonary disease (COPD) are known to increase the risk of cardiovascular events. However, this association has not been investigated specifically in patients with COPD in Japan, whose characteristics may differ from those of Western patients (i.e.

Risk of severe cardiovascular events following COPD exacerbations: results from the EXACOS-CV study in Spain.

Introduction And Objectives: This real-world study-the first of its kind in a Spanish population-aimed to explore severe risk for cardiovascular events and all-cause death following exacerbations in a large cohort of patients with chronic obstructive pulmonary disease (COPD).

Methods: We included individuals with a COPD diagnosis code between 2014 and 2018 from the BIG-PAC health care claims database. The primary outcome was a composite of a first severe cardiovascular event (acute coronary syndrome, heart failure decompensation, cerebral ischemia, arrhythmia) or all-cause death following inclusion in the cohort.

Cardiovascular events after exacerbations of chronic obstructive pulmonary disease: Results from the EXAcerbations of COPD and their OutcomeS in CardioVascular diseases study in Italy.

Introduction: Exacerbations of chronic obstructive pulmonary disease (COPD) can increase the risk of severe cardiovascular events.

Objective: Assess the crude incidence rates (IR) of cardiovascular events and the impact of exacerbations on the risk of cardiovascular events within different time periods following an exacerbation.

Methods: COPD patients aged ≥45 years between 01/01/2015 and 12/31/2018 were identified from the Fondazione Ricerca e Salute administrative database.

Andexanet alfa versus PCC products for factor Xa inhibitor bleeding: A systematic review with meta-analysis.

Previous meta-analyses assessed andexanet alfa (AA) or prothrombin complex concentrate (PCC) products for the treatment of Factor Xa inhibitor (FXaI)-associated major bleeding. However, they did not include recent studies or assess the impact of the risk of bias. We conducted a systematic review with meta-analysis on the effectiveness of AA versus PCC products for FXaI-associated major bleeding, inclusive of the studies' risk of bias.

Factors associated with non-fatal heart failure and atrial fibrillation or flutter within the first 30 days post COPD exacerbation: a nested case-control study.

Background: An immediate, temporal risk of heart failure and arrhythmias after a Chronic Obstructive Pulmonary Disease (COPD) exacerbation has been demonstrated, particularly in the first month post-exacerbation. However, the clinical profile of patients who develop heart failure (HF) or atrial fibrillation/flutter (AF) following exacerbation is unclear. Therefore we examined factors associated with people being hospitalized for HF or AF, respectively, following a COPD exacerbation.

Elucidating the risk of cardiopulmonary consequences of an exacerbation of COPD: results of the EXACOS-CV study in Germany.

Background: Exacerbations of chronic obstructive pulmonary disease (COPD) represent a period of vulnerability. This study explored the association between time periods following an exacerbation and the risk of severe cardiovascular (CV) events or death in Germany.

Methods: A longitudinal cohort study was conducted using routinely collected healthcare data.

Risk of Death and Cardiovascular Events Following an Exacerbation of COPD: The EXACOS-CV US Study.

Purpose: This study estimated the magnitude and duration of risk of cardiovascular events and mortality following acute exacerbations of chronic obstructive pulmonary disease (AECOPD), and whether risks varied by number and severity of exacerbation in a commercially insured population in the United States.

Methods: This was a retrospective cohort study of newly diagnosed COPD patients ≥40 years old in the Healthcare Integrated Research Database from 2012 to 2019. Patients experiencing exacerbations comprised the "exacerbation cohort".

Heightened long-term cardiovascular risks after exacerbation of chronic obstructive pulmonary disease.

Objective: To examine the risk of adverse cardiovascular (CV) events following an exacerbation of chronic obstructive pulmonary disease (COPD).

Methods: This retrospective cohort study identified patients with COPD using administrative data from Alberta, Canada from 2014 to 2019. Exposure periods were 12 months following moderate or severe exacerbations; the reference period was time preceding a first exacerbation.

Temporal Risk of Nonfatal Cardiovascular Events After Chronic Obstructive Pulmonary Disease Exacerbation: A Population-based Study.

Cardiovascular events after chronic obstructive pulmonary disease (COPD) exacerbations are recognized. Studies to date have been analyses of trials, did not differentiate exacerbation severity, included death in the cardiovascular outcome, or had insufficient power to explore individual outcomes temporally. We explore temporal relationships between moderate and severe exacerbations and incident, nonfatal hospitalized cardiovascular events in a primary care-derived COPD cohort.

Risk of cardiovascular events after an exacerbation of chronic obstructive pulmonary disease: results from the EXACOS-CV cohort study using the PHARMO Data Network in the Netherlands.

Background: People living with chronic obstructive pulmonary disease (COPD) have an increased risk of experiencing cardiovascular (CV) events, particularly after an exacerbation. Such CV burden is not yet known for incident COPD patients. We examined the risk of severe CV events in incident COPD patients in periods following either moderate and/or severe exacerbations.

EXAcerbations of COPD and their OutcomeS on CardioVascular diseases (EXACOS-CV) Programme: protocol of multicountry observational cohort studies.

Introduction: In patients with chronic obstructive pulmonary disease (COPD), the risk of certain cardiovascular (CV) events is increased by threefold to fivefold in the year following acute exacerbation of COPD (AECOPD), compared with a non-exacerbation period. While the effect of severe AECOPD is well established, the relationship of moderate exacerbation or prior exacerbation to elevated risk of CV events is less clear. We will conduct cohort studies in multiple countries to further characterise the association between AECOPD and CV events.

The effects of benralizumab on airway geometry and dynamics in severe eosinophilic asthma: a single-arm study design exploring a functional respiratory imaging approach.

Background: Severe eosinophilic asthma (SEA) is characterised by elevated blood/sputum eosinophil counts and airway inflammation, which can lead to mucus plug-mediated airway obstruction, increased exacerbation frequency, declines in lung function, and death. Benralizumab targets the alpha-subunit of the interleukin-5 receptor found on eosinophils, leading to rapid and near complete eosinophil depletion. This is expected to result in reduced eosinophilic inflammation, reduced mucus plugging and improved airway patency and airflow distribution.

Relationship between risk, cumulative burden of exacerbations and mortality in patients with COPD: modelling analysis using data from the ETHOS study.

Background: The major drivers of cost-effectiveness for chronic obstructive pulmonary disease (COPD) therapies are the occurrence of exacerbations and deaths. Exacerbations, including acute and long-term events, can cause worsening of COPD and lead to an increased risk of further exacerbations, and ultimately may elevate the risk of death. In contrast to this, health economic models are based on COPD severity progression.

Population-adjusted indirect treatment comparison of the SOLO1 and PAOLA-1/ENGOT-ov25 trials evaluating maintenance olaparib or bevacizumab or the combination of both in newly diagnosed, advanced BRCA-mutated ovarian cancer.

Background: In the absence of randomised head-to-head trials, we conducted a population-adjusted indirect treatment comparison (PA-ITC) of phase III trial data to evaluate the relative efficacy and safety of maintenance olaparib and bevacizumab alone and in combination in patients with newly diagnosed, advanced ovarian cancer and a BRCA mutation (BRCAm).

Methods: An unanchored PA-ITC was performed on investigator-assessed progression-free survival (PFS) data. Individual patient data from SOLO1 (olaparib versus placebo) and from BRCA-mutated patients in PAOLA-1/ENGOT-ov25 (olaparib plus bevacizumab versus placebo plus bevacizumab) were pooled.

Correlation Between Early Endpoints and Overall Survival in Non-Small-Cell Lung Cancer: A Trial-Level Meta-Analysis.

Early endpoints, such as progression-free survival (PFS), are increasingly used as surrogates for overall survival (OS) to accelerate approval of novel oncology agents. Compiling trial-level data from randomized controlled trials (RCTs) could help to develop a predictive framework to ascertain correlation trends between treatment effects for early and late endpoints. Through trial-level correlation and random-effects meta-regression analysis, we assessed the relationship between hazard ratio (HR) OS and (1) HR PFS and (2) odds ratio (OR) PFS at 4 and 6 months, stratified according to the mechanism of action of the investigational product.

Alternative weighting schemes when performing matching-adjusted indirect comparisons.

Methods for indirect comparisons and network meta-analysis use aggregate level data from multiple studies. A very common, and closely related, scenario is where a company has individual patient data (IPD) from its own trial, but only has published aggregate data from a competitor's trial, and an indirect comparison of the treatments evaluated in these two trials is required. Matching-Adjusted Indirect Comparison (MAIC) has been developed for this situation, where we use the available IPD to adjust for between-trial imbalances in the distributions of observed baseline covariates between the two trials.

Agreement was moderate between data-based and opinion-based assessments of biases affecting randomized trials within meta-analyses.

Background And Objective: Randomized trials included in meta-analyses are often affected by bias caused by methodological flaws or limitations, but the degree of bias is unknown. Two proposed methods adjust the trial results for bias using empirical evidence from published meta-epidemiological studies or expert opinion.

Methods: We investigated agreement between data-based and opinion-based approaches to assessing bias in each of four domains: sequence generation, allocation concealment, blinding, and incomplete outcome data.

Incorporating external evidence on between-trial heterogeneity in network meta-analysis.

In a network meta-analysis, between-study heterogeneity variances are often very imprecisely estimated because data are sparse, so standard errors of treatment differences can be highly unstable. External evidence can provide informative prior distributions for heterogeneity and, hence, improve inferences. We explore approaches for specifying informative priors for multiple heterogeneity variances in a network meta-analysis.

The epidemiology of multimorbidity in primary care: a retrospective cohort study.

Background: Multimorbidity places a substantial burden on patients and the healthcare system, but few contemporary epidemiological data are available.

Aim: To describe the epidemiology of multimorbidity in adults in England, and quantify associations between multimorbidity and health service utilisation.

Design And Setting: Retrospective cohort study, undertaken in England.

Between-trial heterogeneity in meta-analyses may be partially explained by reported design characteristics.

Objective: We investigated the associations between risk of bias judgments from Cochrane reviews for sequence generation, allocation concealment and blinding, and between-trial heterogeneity.

Study Design And Setting: Bayesian hierarchical models were fitted to binary data from 117 meta-analyses, to estimate the ratio λ by which heterogeneity changes for trials at high/unclear risk of bias compared with trials at low risk of bias. We estimated the proportion of between-trial heterogeneity in each meta-analysis that could be explained by the bias associated with specific design characteristics.

Financial incentives improve recognition but not treatment of cardiovascular risk factors in severe mental illness.

Objectives: Severe mental illness (SMI) is associated with premature cardiovascular disease, prompting the UK primary care payment-for-performance system (Quality and Outcomes Framework, QOF) to incentivise annual physical health reviews. This study aimed to assess the QOF's impact on detection and treatment of cardiovascular risk factors in people with SMI.

Methods: A retrospective open cohort study of UK general practice was conducted between 1996 and 2014, using segmented logistic regression with 2004 and 2011 as break points, reflecting the introduction of relevant QOF incentives in these years.

Association of comorbidity and health service usage among patients with dementia in the UK: a population-based study.

Background: The majority of people with dementia have other long-term diseases, the presence of which may affect the progression and management of dementia. This study aimed to identify subgroups with higher healthcare needs, by analysing how primary care consultations, number of prescriptions and hospital admissions by people with dementia varies with having additional long-term diseases (comorbidity).

Methods: A retrospective cohort study based on health data from the Clinical Practice Research Datalink (CPRD) was conducted.

Implementing informative priors for heterogeneity in meta-analysis using meta-regression and pseudo data.

Many meta-analyses combine results from only a small number of studies, a situation in which the between-study variance is imprecisely estimated when standard methods are applied. Bayesian meta-analysis allows incorporation of external evidence on heterogeneity, providing the potential for more robust inference on the effect size of interest. We present a method for performing Bayesian meta-analysis using data augmentation, in which we represent an informative conjugate prior for between-study variance by pseudo data and use meta-regression for estimation.

Two new methods to fit models for network meta-analysis with random inconsistency effects.

Background: Meta-analysis is a valuable tool for combining evidence from multiple studies. Network meta-analysis is becoming more widely used as a means to compare multiple treatments in the same analysis. However, a network meta-analysis may exhibit inconsistency, whereby the treatment effect estimates do not agree across all trial designs, even after taking between-study heterogeneity into account.