Annals of the American Thoracic Society最新文献

Rationale: Although recent evidence suggested that glucagon-like peptide 1 receptor agonists (GLP1RAs) might reduce the risk of asthma exacerbations, it remains unclear which subpopulations might derive the most benefit from GLP1RA treatment. Objectives: To identify characteristics of patients with asthma that predict who might benefit the most from GLP1RA treatment using real-world data. Methods: We implemented an active-comparator, new-user design analysis using commercially ensured patients 18-65 years of age from MarketScan data for 2007-2019 and identified two cohorts: GLP1RAs versus thiazolidinediones and GLP1RAs versus sulfonylureas. The outcome was acute exacerbation of asthma (hospital admission or emergency department visit for asthma) within 180 days after initiation. We applied iterative causal forest, a novel causal machine learning subgrouping algorithm, to assess heterogeneous treatment effects. In identified subgroups, we predicted propensity score, conducted propensity score trimming, and then estimated adjusted risk differences for the effect of GLP1RAs relative to comparators on asthma exacerbation using inverse probability treatment weighting in the propensity score-trimmed subpopulation. Results: Among 10,989 patients initiating GLP1RAs or thiazolidinediones and 17,088 patients initiating GLP1RAs versus sulfonylurea, GLP1RA initiators had fewer exacerbations, with adjusted risk differences of -0.5% (95% confidence interval [CI], -1.1% to 0.1%) and -1.6% (95% CI, -2.2% to -1.1%), respectively. In the GLP1RA versus sulfonylurea cohort, in which we observed a beneficial effect, our iterative causal forest analysis identified five subgroups with different treatment effects, defined by the number of emergency department visits, the number of prescriptions for short-acting β₂-agonists, the number of prescriptions for inhaled steroids and long-acting β-agonists (either combination therapy or concurrent use), and age ≥ 50 years. Among these, patients with two or more emergency department visits during the 12-month baseline period had the largest absolute exacerbation risk reduction, with a decrease of 2.8% for GLP1RAs (95% CI, -4.8% to -0.9%). Conclusions: GLP1RAs demonstrated a beneficial effect on reducing asthma exacerbation relative to sulfonylureas. Patients with asthma with two or more emergency department visits (a proxy for disease severity) benefit most from GLP1RAs. Emergency department visit frequency, the number of maintenance and reliever inhalers, and age might help individualize prediction of the short-term benefit of GLP1RAs on asthma exacerbation.

Rationale: Sepsis care delivery-including the initiation of prompt, appropriate antimicrobials-remains suboptimal. Objectives: This study was conducted to determine direct and off-target effects of emergency department (ED) sepsis care reorganization. Methods: This pragmatic pilot trial enrolled adult patients who presented from November 2019 to February 2021 to an ED in Utah before and after implementation of a multimodal, team-based "Code Sepsis" protocol. Patients who presented to two other EDs where usual care was continued served as contemporaneous control subjects. The primary outcome was door-to-antimicrobial time among patients meeting Sepsis-3 criteria before ED departure. Secondary and safety outcomes included all-cause 30-day mortality, antimicrobial utilization and overtreatment, and antimicrobial-associated adverse events. Multivariable regression analyses used difference-in-differences methods to account for trends in outcomes unrelated to the studied intervention. Results: Code Sepsis protocol activation (N = 307) exhibited 8.5% sensitivity and 66% positive predictive value for patients meeting sepsis criteria before ED departure. Among 10,151 patients who met sepsis criteria during the study, adjusted difference-in-differences analysis demonstrated a 13-minute (95% confidence interval = 7-19) decrease in door-to-antimicrobial time associated with Code Sepsis implementation (P < 0.001). Mortality and clinical safety outcomes were unchanged, but Code Sepsis implementation was associated with increased false-positive presumptive infection diagnoses among patients who met sepsis criteria in the ED and increased antimicrobial utilization. Conclusions: Implementation of a team-based protocol for rapid sepsis evaluation and treatment during the coronavirus disease (COVID-19) pandemic's first year was associated with decreased ED door-to-antimicrobial time but also increased antimicrobial utilization. Measurement of both patient-centered and off-target effects of sepsis care improvement interventions is essential to comprehensive assessment of their value. Clinical trial registered with www.clinicaltrials.gov (NCT04148989).

Rationale: Fibrosing mediastinitis (FM) is an uncommon fibroinflammatory condition without established or effective medical therapies. Infiltrating B lymphocytes are commonly present, and progressive fibrosis compromises mediastinal structures, including blood vessels and airways, resulting in significant morbidity and mortality. Objective: To evaluate the benefits and side effects of rituximab in patients with progressive and symptomatic FM. Methods: We treated 22 patients (median age, 35 yr; range, 15-68 yr; 45% female) with metabolically active, progressive FM with rituximab on an off-label basis. Additionally, patients were administered pneumocystis and antifungal prophylaxis when immunosuppressed with rituximab. Modeling of longitudinal treatment response based on changes in relative lesion volume from baseline was performed retrospectively using functional data analysis, and time-to-event modeling was performed to estimate treatment response rates based on a >30% reduction in pretreatment volume. The primary endpoints were lack of disease progression and change in mediastinal lesion volume on computed tomography (evaluated retrospectively). Results: No patient experienced disease progression after rituximab therapy. Median clinical follow-up was 42 months (range, 7-94 mo) and imaging follow-up 21 months (range, 7-62 mo). A total of 82% of patients had confirmed histoplasmosis-associated FM. After rituximab treatment, a 49.6% (95% confidence interval, 17.5-64.4%) mean estimated decrease in pretreatment lesion volume was observed at 24 months. The estimated objective treatment response rate was 47.9% (95% confidence interval, 26.7-70.3%). Conclusions: This observational study suggests that rituximab is a well tolerated and potentially effective therapy in a cohort of patients with symptomatic and progressive FM.

Rationale: High costs of controller therapies may be a barrier to guideline-recommended asthma treatment. Objectives: We determined whether eliminating out-of-pocket (OOP) payments among low-income patients with asthma impacted controller medication use. Methods: We applied a controlled interrupted time series design to administrative claims data in British Columbia, Canada from 2017 to 2020. Cases were individuals with an annual household income <$13,750 in whom copays were eliminated in January 2019; there was no change in public coverage for the control group with annual income >$45,000. We evaluated trends in asthma medication costs, use, the ratio of inhaled corticosteroid-containing medications to all asthma medications, excessive use of short-acting β-agonists (more than one canister per month), and the proportion of days covered by controller therapies. Results: There were 12,940 cases (62% female; mean age, 30.3 yr; standard deviation [SD], 14.9) and 71,331 controls (55% female; mean age, 31.3 yr; SD, 16.3). Removal of OOP payments increased monthly mean medication costs by $3.32 (95% confidence interval [CI], $0.08 to $6.56, 2020 Canadian dollars), days' supply of controller medications by 1.50 days (95% CI, 0.61 to 2.40 d), and the ratio of inhaled corticosteroid-containing medications to total medications by 4.20% (95% CI, 0.73% to 7.66%) compared with the control group. The policy had no effect on the proportion of days covered by controller therapies (0.01; 95% CI, -0.01 to 0.04), but nonsignificantly decreased the percentage of patients with excessive short-acting β-agonist use (-6.37%; 95% CI, -12.90% to 0.16%). Conclusions: Removal of OOP payments increased the dispensation of controller therapies, suggesting cost-related nonadherence could impair optimal asthma management.

Rationale: Current critical care practice does not integrate social determinants of health (SDOH) in systematic or standardized ways. Routine assessment of SDOH in the intensive care unit (ICU) may improve clinical decision making, patient- and family-centered outcomes, and clinician well-being. Objective: Given that the appropriateness and feasibility of SDOH assessment in the ICU is unknown, we aimed to understand how ICU clinicians think about and use SDOH. Methods: We conducted semistructured interviews with clinicians focused on barriers to and facilitators of assessing SDOH during critical illness and perceptions of screening for SDOH in the ICU. We used chart-stimulated recall to assist clinicians in reflecting on how SDOH applied to and was used in patients' care. After deidentifying interviews, we analyzed transcripts guided by a thematic analysis approach using a combination of inductive and deductive coding, the latter framed within the Centers for Disease Control and Prevention SDOH Healthy People framework. Results: We completed interviews with 30 clinicians in a variety of professional roles. The majority of clinicians self-identified as men (n = 17; 56.7%) of White race (n = 25; 83.3%). Clinicians contextualize their use of SDOH within three frames of reference: 1) their own identity and experiences; 2) their relationships and communication with patients and caregivers; and 3) immediate structures of care around ICU patients, including clinician advocacy, care transitions, and readmission. Clinicians identified that discussing SDOH could allow them to recognize bias faced by their patients, elucidate drivers of critical illness, and navigate communication with patients' caregivers. Clinicians worried about ICU-specific factors impeding the discussion of SDOH, including time constraints and acuity, high stakes and emotions, and negative anticipatory emotions. Conclusions: Clinicians gather SDOH during critical illness both to understand their patients' stories and to provide individualized care, which may lead to better clinician satisfaction and patient- and family-centered care outcomes. Educational and operational efforts to increase SDOH assessment and use in critical care should also gather and integrate the perspectives of patients and caregivers regarding the collection and use of SDOH in the ICU.