Adherence-enhancing interventions for pharmacological and oxygen therapy in patients with COPD: a systematic review and component network meta-analyses.

INTRODUCTION: Adherence to COPD management strategies is complex, and it is unclear which intervention may enhance it. OBJECTIVES: We aim to evaluate the effectiveness of adherence-enhancing interventions, alone or compared to interventions, for patients with COPD. METHODS: This review comprises a component network meta-analysis with a structured narrative synthesis. We searched MEDLINE, Embase, CENTRAL, CINAHL and trial registries on 9 September 2023. We included controlled studies that explored adherence in patients with COPD. Two review authors independently performed the study selection, data extraction and the risk of bias assessment. We involved patients with COPD in developing this systematic review through focus group interviews and displayed the findings in pre-designed logic models. RESULTS: We included 33 studies with 5775 participants. We included 13 studies in the component network meta-analysis that explored adherence. It was mainly assessed through questionnaires. As a continuous outcome, there was a tendency mainly for education (standardised mean difference 1.26, 95% CI 1.13-1.38, very low certainty of evidence) and motivation (mean difference 1.85, 95% CI 1.19-2.50, very low certainty of evidence) to improve adherence. As a dichotomous outcome (e.g. adherent/non-adherent), we found a possible benefit with education (odds ratio 4.77, 95% CI 2.25-10.14, low certainty of evidence) but not with the other components. We included six studies that reported quality of life in the component network meta-analysis. Again, we found a benefit of education (mean difference -9.70, 95% CI -10.82- -8.57, low certainty of evidence) but not with the other components. CONCLUSIONS: Education may improve adherence and quality of life in COPD patients. Patient focus group interviews indicated that interventions that strengthen patients' self-efficacy and help them to achieve individual goals are the most helpful.

Safety outcomes of direct oral anticoagulants in older adults with atrial fibrillation: a systematic review and meta-analysis of (subgroup analyses from) randomized controlled trials.

Balancing stroke prevention and risk of bleeding in patients with atrial fibrillation (AF) is challenging. Direct oral anticoagulants (DOACs) are by now considered standard of care for treating patients with AF in international guidelines. Our objective was to assess the safety of long-term intake of DOACs in older adults with AF. We included RCTs in elderly (≥ 65 years) patients with AF. A systematic search in MEDLINE and EMBASE was performed on 19 April 2022. For determination of risk of bias, the RoB 2 tool was applied. We pooled outcomes using random-effects meta-analyses. The quality of evidence was assessed using GRADE. Eleven RCTs with a total of 63,374 patients were identified. Two RCTs compared apixaban with either warfarin or aspirin, four edoxaban with either placebo, aspirin, or vitamin K antagonists (VKAs), two dabigatran with warfarin and three rivaroxaban with warfarin. DOACs probably reduce mortality in elderly patients with AF (HR 0.89 95%CI 0.77 to 1.02). Low-dose DOACs likely reduce bleeding compared to VKAs (HR ranged from 0.47 to 1.01). For high-dose DOACS the risk of bleeding varied widely (HR ranged from 0.80 to 1.40). We found that low-dose DOACs probably decrease mortality in AF patients. Moreover, apixaban and probably edoxaban are associated with fewer major or clinically relevant bleeding (MCRB) events compared to VKAs. For dabigatran and rivaroxaban, the risk of MCRB varies depending on dose. Moreover, subgroup analyses indicate that in the very old (≥ 85) the risk for MCRB events might be increased when using DOACs.Registration: PROSPERO: CRD42020187876.

Adherence enhancing interventions for pharmacological and oxygen therapy in patients with COPD: protocol for a systematic review and component network meta-analyses.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by hyperinflation and expiratory airflow limitation due to long-term exposure to irritants. The variety and complexity of COPD treatment and the possible added comorbidities may make the patients find it difficult to cope with the required medications. That is why supporting patients' adherence is critical because not taking medications correctly increases the risk of complications and creates an additional financial burden. A range of interventions aiming to improve patient adherence were used, and most of them are complex since they involve a mix of elements. Furthermore, despite the variety of available tools, assessing adherence is challenging because clinicians usually do not get a concrete judgement if their patients followed their treatment plan reliably. We aim to evaluate the effectiveness of adherence-enhancing interventions for COPD patients, explore which intervention (component) works for which patients and check the factors influencing the implementation and participant responses. METHODS: We will perform a comprehensive literature search (Medline, Embase, Cochrane Library, trial registries) without restrictions on language and publication status, and we will include all controlled studies investigating the effect of adherence-enhancing intervention on patients with COPD. We plan to involve COPD patients in the systematic review development through two patient interviews (one before and one after the systematic review). Two reviewers will perform the screening, data extraction and risk of bias (ROB) assessment. For ROB, we will use ROB 2.0 to assess randomised controlled trials, and ROBINS-I to assess non-randomised studies. We will perform pair-wise random-effects meta-analyses and component network meta-analyses to identify the most effective components and combinations of components. We will use the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to assess the quality of evidence. To determine the degree of complexity, we will use the iCAT_SR checklist, and then, following a logical model, we will group the interventions according to prespecified criteria. DISCUSSION: This systematic review aims to point out the most effective and implementable adherence-enhancing interventions by using methods for synthesising evidence on complex interventions and involving COPD patients all along with the review process. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022353977.

Blinded continuous information monitoring of recurrent event endpoints with time trends in clinical trials.

Blinded sample size re-estimation and information monitoring based on blinded data has been suggested to mitigate risks due to planning uncertainties regarding nuisance parameters. Motivated by a randomized controlled trial in pediatric multiple sclerosis (MS), a continuous monitoring procedure for overdispersed count data was proposed recently. However, this procedure assumed constant event rates, an assumption often not met in practice. Here we extend the procedure to accommodate time trends in the event rates considering two blinded approaches: (a) the mixture approach modeling the number of events by a mixture of two negative binomial distributions and (b) the lumping approach approximating the marginal distribution of the event counts by a negative binomial distribution. Through simulations the operating characteristics of the proposed procedures are investigated under decreasing event rates. We find that the type I error rate is not inflated relevantly by either of the monitoring procedures, with the exception of strong time dependencies where the procedure assuming constant rates exhibits some inflation. Furthermore, the procedure accommodating time trends has generally favorable power properties compared with the procedure based on constant rates which stops often too late. The proposed method is illustrated by the clinical trial in pediatric MS.