Effect of Adherence to Inhaled Pharmacologic Therapy on Chronic Obstructive Pulmonary Disease (COPD) Exacerbations and Death Among U.S. Veterans
Bibliographic record
Abstract
Abstract Rationale: Substantial evidence from rigorously controlled clinical trials demonstrates the benefit of combination long-acting inhaled therapies to reduce future exacerbations and improve symptoms among patients with a recent COPD exacerbation. However, the effect of adherence to these therapies on patient outcomes in clinical practice is poorly understood. We hypothesized that increased adherence would be associated with lower occurrence of COPD exacerbation and death. Methods: We conducted a national cohort study of patients discharged after hospitalization for a COPD exacerbation at Veterans Affairs (VA) medical centers from 2010-2019. We restricted the cohort to patients receiving current guideline-recommended therapy with dual long-acting bronchodilators (long-acting beta agonists (LABA) and long-acting muscarinic antagonists (LAMA)) or triple therapy (LABA/LAMA and inhaled corticosteroid (ICS)). We assessed adherence to LAMA/LABA or LAMA/LABA/ICS therapy 3 months after discharge and excluded patients who died or experienced a repeat exacerbation during this time. We measured adherence using the ReComp score, a standardized metric representing the proportion of days a medication is available based on pharmacy fills. Our primary exposure was a dichotomous measure with adherence defined as ReComp ≥0.8 across all inhaled therapies. In secondary analyses, we examined ReComp as a categorical and continuous measure averaged across therapies. The primary composite outcome was any COPD exacerbation or death 3-6 months after hospital discharge. We used mixed effects logistic regression to test the association of the outcome with medication adherence using VA facility as a random effect and adjusting for demographics, smoking status, comorbidities, health care utilization, and indicators of disease severity. Results: Of 20,259 patients included in the cohort, 20% (n=4,022) experienced the primary composite outcome. Patients tended to be older, White males (average age 69 years, 78.7% White, and 96.3% male). Approximately 31% (n=6,318) met adherence criteria for all prescribed therapies. Overall, adherence to inhaled therapies was not associated with the composite outcome of COPD exacerbation or death (Table 1). Adherence also wasn't associated with the individual components of the composite outcome, except for a decrease in mortality associated with increasing adherence using continuous ReComp scores. Conclusion: Overall, adherence was poor. We did not observe a difference in COPD exacerbation or death among patients who were adherent to inhaled therapies. These findings suggest that adherence to inhaled therapies, as measured using claims data, is insufficient to improve COPD outcomes and other factors such as actual inhaler usage or inhaler technique may contribute to similar outcomes regardless of measured adherence.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.011 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".