Describing diversity of real world data sources in pharmacoepidemiologic studies: The DIVERSE scoping review.

PURPOSE: Real-world evidence (RWE) is increasingly used for medical regulatory decisions, yet concerns persist regarding its reproducibility and hence validity. This study addresses reproducibility challenges associated with diversity across real-world data sources (RWDS) repurposed for secondary use in pharmacoepidemiologic studies. Our aims were to identify, describe and characterize practices, recommendations and tools for collecting and reporting diversity across RWDSs, and explore how leveraging diversity could improve the quality of evidence. METHODS: In a preliminary phase, keywords for a literature search and selection tool were designed using a set of documents considered to be key by the coauthors. Next, a systematic search was conducted up to December 2021. The resulting documents were screened based on titles and abstracts, then based on full texts using the selection tool. Selected documents were reviewed to extract information on topics related to collecting and reporting RWDS diversity. A content analysis of the topics identified explicit and latent themes. RESULTS: Across the 91 selected documents, 12 topics were identified: 9 dimensions used to describe RWDS (organization accessing the data source, data originator, prompt, inclusion of population, content, data dictionary, time span, healthcare system and culture, and data quality), tools to summarize such dimensions, challenges, and opportunities arising from diversity. Thirty-six themes were identified within the dimensions. Opportunities arising from data diversity included multiple imputation and standardization. CONCLUSIONS: The dimensions identified across a large number of publications lay the foundation for formal guidance on reporting diversity of data sources to facilitate interpretation and enhance replicability and validity of RWE.

Impact of COPD and asthma on in-hospital mortality and management of patients with heart failure in England and Wales: an observational analysis.

OBJECTIVE: To evaluate the association between having concomitant chronic obstructive pulmonary disease (COPD) or asthma, and in-patient mortality and post-discharge management among patients hospitalised for acute heart failure (HF). SETTING: Data were obtained from patients enrolled in the National Heart Failure Audit. PARTICIPANTS: 217 329 patients hospitalised for HF in England-Wales between March 2012 and 2018. OUTCOMES: In-hospital mortality, referrals to cardiology follow-up and prescriptions for HF medications were compared between patients with comorbid COPD (COPD-HF) or asthma (asthma-HF) versus HF-alone using mixed-effects logistic regression. RESULTS: Patients with COPD-HF were more likely to die during hospitalisation, and those with asthma-HF had a reduced likelihood of death, compared with patients who had HF-alone ((adjusted)ORadj, 95% CI: 1.10, 1.06 to 1.14 and ORadj, 95% CI: 0.84, 0.79 to 0.88). In patients who survived to discharge, referral to HF follow-up services differed between groups: patients with COPD-HF had reduced odds of cardiology follow-up (ORadj, 95% CI 0.79, 0.77 to 0.81), while cardiology referral odds for asthma-HF were similar to HF-alone. Overall, proportions of HF medication prescriptions at discharge were low for both COPD-HF and asthma-HF groups, particularly prescriptions for beta-blockers. CONCLUSIONS: In this nationwide analysis, we showed that COPD and asthma significantly impact the clinical course in patients hospitalised for HF. COPD is associated with higher in-patient mortality and lower cardiology referral odds, while COPD and asthma are both associated with lower use of prognostic HF therapies on discharge. These data highlight therapeutic gaps and a need for better integration of cardiopulmonary services to improve healthcare provision for patients with HF and coexisting respiratory disease.

Differences in Outcomes between Heart Failure Phenotypes in Patients with Coexistent Chronic Obstructive Pulmonary Disease: A Cohort Study.

Rationale: Differences in clinical presentation and outcomes between heart failure (HF) phenotypes in patients with chronic obstructive pulmonary disease (COPD) have not been assessed. Objectives: The aim of this study was to compare clinical outcomes and healthcare resource use between patients with COPD and HF with preserved ejection fraction (HFpEF), mildly reduced ejection fraction (HFmEF), and reduced ejection fraction (HFrEF). Methods: Patients with COPD and HF were identified in the U.S. administrative claims database OptumLabs DataWarehouse between 2008 and 2018. All-cause and cause-specific (HF) hospitalization, acute exacerbation of COPD (AECOPD, severe and moderate combined), mortality, and healthcare resource use were compared between HF phenotypes. Results: From 5,419 patients with COPD, 70% had HFpEF, 20% had HFrEF, and 10% had HFmEF. All-cause hospitalization did not differ across groups; however, patients with COPD and HFrEF had a greater risk of HF-specific hospitalization (hazard ratio [HR], 1.54; 95% confidence interval [CI], 1.29-1.84) and mortality (HR, 1.17; 95% CI, 1.03-1.33) than patients with COPD and HFpEF. Conversely, patients with COPD and HFrEF had a lower risk of AECOPD than those with COPD and HFpEF (HR, 0.75; 95% CI, 0.66-0.87). Rates of long-term stays (in skilled-nursing facilities) and emergency room visits were lower for those with COPD and HFrEF than for those with COPD and HFpEF. Conclusions: Outcomes in patients with comorbid COPD and HFpEF are largely driven by COPD. Given the paucity in treatments for HFpEF, better differentiation between cardiac and respiratory symptoms may provide an opportunity to reduce the risk of AECOPD. Risk of death and HF hospitalization were highest among patients with COPD and HFrEF, emphasizing the importance of optimizing guideline-recommended HFrEF therapies in this group.

GP consultation rates for sequelae after acute covid-19 in patients managed in the community or hospital in the UK: population based study.

OBJECTIVES: To describe the rates for consulting a general practitioner (GP) for sequelae after acute covid-19 in patients admitted to hospital with covid-19 and those managed in the community, and to determine how the rates change over time for patients in the community and after vaccination for covid-19. DESIGN: Population based study. SETTING: 1392 general practices in England contributing to the Clinical Practice Research Datalink Aurum database. PARTICIPANTS: 456 002 patients with a diagnosis of covid-19 between 1 August 2020 and 14 February 2021 (44.7% men; median age 61 years), admitted to hospital within two weeks of diagnosis or managed in the community, and followed-up for a maximum of 9.2 months. A negative control group included individuals without covid-19 (n=38 511) and patients with influenza before the pandemic (n=21 803). MAIN OUTCOME MEASURES: Comparison of rates for consulting a GP for new symptoms, diseases, prescriptions, and healthcare use in individuals admitted to hospital and those managed in the community, separately, before and after covid-19 infection, using Cox regression and negative binomial regression for healthcare use. The analysis was repeated for the negative control and influenza cohorts. In individuals in the community, outcomes were also described over time after a diagnosis of covid-19, and compared before and after vaccination for individuals who were symptomatic after covid-19 infection, using negative binomial regression. RESULTS: Relative to the negative control and influenza cohorts, patients in the community (n=437 943) had significantly higher GP consultation rates for multiple sequelae, and the most common were loss of smell or taste, or both (adjusted hazard ratio 5.28, 95% confidence interval 3.89 to 7.17, P<0.001); venous thromboembolism (3.35, 2.87 to 3.91, P<0.001); lung fibrosis (2.41, 1.37 to 4.25, P=0.002), and muscle pain (1.89, 1.63 to 2.20, P<0.001); and also for healthcare use after a diagnosis of covid-19 compared with 12 months before infection. For absolute proportions, the most common outcomes ≥4 weeks after a covid-19 diagnosis in patients in the community were joint pain (2.5%), anxiety (1.2%), and prescriptions for non-steroidal anti-inflammatory drugs (1.2%). Patients admitted to hospital (n=18 059) also had significantly higher GP consultation rates for multiple sequelae, most commonly for venous thromboembolism (16.21, 11.28 to 23.31, P<0.001), nausea (4.64, 2.24 to 9.21, P<0.001), prescriptions for paracetamol (3.68, 2.86 to 4.74, P<0.001), renal failure (3.42, 2.67 to 4.38, P<0.001), and healthcare use after a covid-19 diagnosis compared with 12 months before infection. For absolute proportions, the most common outcomes ≥4 weeks after a covid-19 diagnosis in patients admitted to hospital were venous thromboembolism (3.5%), joint pain (2.7%), and breathlessness (2.8%). In patients in the community, anxiety and depression, abdominal pain, diarrhoea, general pain, nausea, chest tightness, and tinnitus persisted throughout follow-up. GP consultation rates were reduced for all symptoms, prescriptions, and healthcare use, except for neuropathic pain, cognitive impairment, strong opiates, and paracetamol use in patients in the community after the first vaccination dose for covid-19 relative to before vaccination. GP consultation rates were also reduced for ischaemic heart disease, asthma, and gastro-oesophageal disease. CONCLUSIONS: GP consultation rates for sequelae after acute covid-19 infection differed between patients with covid-19 who were admitted to hospital and those managed in the community. For individuals in the community, rates of some sequelae decreased over time but those for others, such as anxiety and depression, persisted. Rates of some outcomes decreased after vaccination in this group.

Beta-blocker therapy in patients with COPD: a systematic literature review and meta-analysis with multiple treatment comparison.

BACKGROUND: Beta-blockers are associated with reduced mortality in patients with cardiovascular disease but are often under prescribed in those with concomitant COPD, due to concerns regarding respiratory side-effects. We investigated the effects of beta-blockers on outcomes in patients with COPD and explored within-class differences between different agents. METHODS: We searched the Cochrane Central Register of Controlled Trials, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Medline for observational studies and randomized controlled trials (RCTs) investigating the effects of beta-blocker exposure versus no exposure or placebo, in patients with COPD, with and without cardiovascular indications. A meta-analysis was performed to assess the association of beta-blocker therapy with acute exacerbations of COPD (AECOPD), and a network meta-analysis was conducted to investigate the effects of individual beta-blockers on FEV1. Mortality, all-cause hospitalization, and quality of life outcomes were narratively synthesized. RESULTS: We included 23 observational studies and 14 RCTs. In pooled observational data, beta-blocker therapy was associated with an overall reduced risk of AECOPD versus no therapy (HR 0.77, 95%CI 0.70 to 0.85). Among individual beta-blockers, only propranolol was associated with a relative reduction in FEV1 versus placebo, among 199 patients evaluated in RCTs. Narrative syntheses on mortality, all-cause hospitalization and quality of life outcomes indicated a high degree of heterogeneity in study design and patient characteristics but suggested no detrimental effects of beta-blocker therapy on these outcomes. CONCLUSION: The class effect of beta-blockers remains generally positive in patients with COPD. Reduced rates of AECOPD, mortality, and improved quality of life were identified in observational studies, while propranolol was the only agent associated with a deterioration of lung function in RCTs.

Model-based comorbidity clusters in patients with heart failure: association with clinical outcomes and healthcare utilization.

BACKGROUND: Comorbidities affect outcomes in heart failure (HF), but are not reflected in current HF classification. The aim of this study is to characterize HF groups that account for higher-order interactions between comorbidities and to investigate the association between comorbidity groups and outcomes. METHODS: Latent class analysis (LCA) was performed on 12 comorbidities from patients with HF identified from administrative claims data in the USA (OptumLabs Data Warehouse®) between 2008 and 2018. Associations with admission to hospital and mortality were assessed with Cox regression. Negative binomial regression was used to examine rates of healthcare use. RESULTS: In a population of 318,384 individuals, we identified five comorbidity clusters, named according to their dominant features: low-burden, metabolic-vascular, anemic, ischemic, and metabolic. Compared to the low-burden group (minimal comorbidities), patients in the metabolic-vascular group (exhibiting a pattern of diabetes, obesity, and vascular disease) had the worst prognosis for admission (HR 2.21, 95% CI 2.17-2.25) and death (HR 1.87, 95% CI 1.74-2.01), followed by the ischemic, anemic, and metabolic groups. The anemic group experienced an intermediate risk of admission (HR 1.49, 95% CI 1.44-1.54) and death (HR 1.46, 95% CI 1.30-1.64). Healthcare use also varied: the anemic group had the highest rate of outpatient visits, compared to the low-burden group (IRR 2.11, 95% CI 2.06-2.16); the metabolic-vascular and ischemic groups had the highest rate of admissions (IRR 2.11, 95% CI 2.08-2.15, and 2.11, 95% CI 2.07-2.15) and healthcare costs. CONCLUSIONS: These data demonstrate the feasibility of using LCA to classify HF based on comorbidities alone and should encourage investigation of multidimensional approaches in comorbidity management to reduce admission and mortality risk among patients with HF.

Utility value estimates in cardiovascular disease and the effect of changing elicitation methods: a systematic literature review.

OBJECTIVE: Identify the most recent utility value estimates for cardiovascular disease (CVD) via systematic literature review (SLR) and explore trends in utility elicitation methods in the last 6 years. METHODS: This SLR was updated on January 25, 2018, and identified studies reporting utilities for myocardial infarction (MI), stroke, angina, peripheral artery disease (PAD), and any-cause revascularization by searching Embase, PubMed, Health Technology Assessment Database, and grey literature. RESULTS: A total of 375 studies reported CVD utilities (pre-2013 vs post-2013: MI, 38 vs 32; stroke, 86 vs 113; stable angina, 8 vs 9; undefined/unstable angina, 23 vs 8; PAD, 29 vs 13; revascularization, 54 vs 40). Median average utilities for MI, stroke, and revascularization increased over time (pre-2013 vs post-2013: MI, 0.71 vs 0.79; stroke, 0.63 vs 0.64; revascularization, 0.76 vs 0.81); angina and PAD showed a decrease in median values over time (stable angina, 0.83 vs 0.72; undefined/unstable angina, 0.70 vs 0.69; PAD, 0.76 vs 0.71). The proportion of utility estimates from trials increased across health states (pre-2013 vs post-2013: 22.5% vs 37.2%), as did the proportion of trials using the EuroQol Five Dimensions Questionnaire (EQ-5D; pre-2013 vs post-2013: 73.8% vs 91.4%). Use of methods such as the standard gamble, time trade-off, and Health Utilities Index has declined. CONCLUSIONS: Health state utilities for cardiovascular health states have changed in the last 6 years, likely due to changes in the types of studies conducted, the patient populations evaluated, and possibly changing utility elicitation methods. The EQ-5D has been used more frequently.

Impact of chronic obstructive pulmonary disease on readmission after hospitalization for acute heart failure: A nationally representative US cohort study.

BACKGROUND: Patients hospitalized for heart failure (HF) are at high risk of readmission. Chronic obstructive pulmonary disease (COPD) is one of the most prevalent comorbidities in this population. However, few data and only small studies describe the impact of COPD on the risk of readmission. METHODS AND RESULTS: Hospitalizations for HF were identified in the 2012 National Readmissions Database. We compared clinical characteristics and the risk of all-cause, cardiovascular (CV) and respiratory-related readmission for patients with and without COPD. We included 225,160 patients hospitalized for HF among whom 54,953 had comorbid COPD. Patients with COPD were younger (median age 76 years COPD versus 77 years without COPD; p < 0.001), had a higher burden of comorbidity and were more frequently male (53% versus 49%, p < 0.001). Thirty-day all-cause readmission risk was two-fold greater in patients with COPD compared to those without COPD (adjusted HR 2.02, 95%CI 1.97-2.08). Most readmissions were attributed to a CV cause, though fewer patients with COPD had a CV admission (49% versus 51% without COPD). COPD was independently associated with significantly more frequent unplanned respiratory-related readmission (adjusted HR 2.90, 95%CI 2.68-3.15) as well as CV readmission risk (adjusted HR 1.92, 95%CI 1.85-1.99). CONCLUSIONS: In patients hospitalized for HF, most readmissions are due to a CV cause. However, patients with comorbid COPD are at a significantly elevated risk of respiratory in addition to CV-related readmission. These data stress the importance of a multidisciplinary management approach, including optimization of non-CV conditions, in order to reduce readmissions post index HF hospitalization.

Effect of beta-blocker therapy on clinical outcomes, safety, health-related quality of life and functional capacity in patients with chronic obstructive pulmonary disease (COPD): a protocol for a systematic literature review and meta-analysis with multiple treatment comparison.

INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD) who have a clinical indication for beta-blocker therapy, are often not prescribed such medication, despite evidence suggesting that beta-blockers are not associated with adverse respiratory outcomes. The primary objective of this systematic review and meta-analysis is to examine the class effect of beta-blocker use in patients with COPD. We will focus on a broad range of endpoints including, clinical, safety, and patient-centric outcomes such as health related quality of life (HRQoL) and functional capacity. A secondary objective is to explore potential within-class variation in the effects of beta-blockers among patients with COPD, and rank individual agents according to their relative benefit(s). METHODS AND ANALYSIS: MEDLINE, Embase, The Cochrane Library and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases will be systematically searched, from inception to present, to identify randomised controlled trials (RCTs) and other prospective and interventional studies of beta-blocker use in patients with COPD which report on the outcomes of interest. Relative treatment effects with respect to mortality, COPD exacerbations, all-cause hospitalisation, lung function, HRQoL and exercise capacity will be summarised by meta-analysis. Individual treatments (agents) will be compared in a Bayesian network meta-analysis including RCT and observational data, if feasible. ETHICS AND DISSEMINATION: The results of the study will be submitted for publication in a peer-reviewed journal. Only previously published aggregate data will be used for the purpose of this review. PROSPERO REGISTRATION NUMBER: CRD42018098983.

Assessing Social Networks in Patients with Psychotic Disorders: A Systematic Review of Instruments.

BACKGROUND: Evidence suggests that social networks of patients with psychotic disorders influence symptoms, quality of life and treatment outcomes. It is therefore important to assess social networks for which appropriate and preferably established instruments should be used. AIMS: To identify instruments assessing social networks in studies of patients with psychotic disorders and explore their properties. METHOD: A systematic search of electronic databases was conducted to identify studies that used a measure of social networks in patients with psychotic disorders. RESULTS: Eight instruments were identified, all of which had been developed before 1991. They have been used in 65 studies (total N of patients = 8,522). They assess one or more aspects of social networks such as their size, structure, dimensionality and quality. Most instruments have various shortcomings, including questionable inter-rater and test-retest reliability. CONCLUSIONS: The assessment of social networks in patients with psychotic disorders is characterized by a variety of approaches which may reflect the complexity of the construct. Further research on social networks in patients with psychotic disorders would benefit from advanced and more precise instruments using comparable definitions of and timescales for social networks across studies.