Chander, Subhash

Background/Objectives: Fixed-dose triple therapy is recommended for patients with chronic obstructive pulmonary disease (COPD) at high risk of exacerbations; however, direct comparative effectiveness data between available triple therapy regimens remain limited. We compared real-world clinical outcomes among adults with COPD receiving fluticasone furoate/vilanterol/umeclidinium (FF/VI/UMEC) or budesonide/glycopyrrolate/formoterol (BUD/GLY/FOR). Methods: We conducted a retrospective propensity score-matched cohort study using the TriNetX Research Network. Adults with a spirometrically confirmed diagnosis of COPD who received fluticasone furoate/vilanterol/umeclidinium (FF/VI/UMEC) or budesonide/glycopyrrolate/formoterol (BUD/GLY/FOR) between July 2020 and August 2024 were included in the analysis. A 365-day landmark period was applied to establish maintenance therapy, with outcome follow-up beginning 1 year after treatment initiation. Patients were followed for outcomes through August 2025, the date of database analysis. After 1:1 propensity score matching, treatment groups were compared for COPD exacerbations, acute respiratory failure (ARF), hospitalization, and all-cause mortality using RR and Cox proportional hazards analyses. Results: In matched cohorts, FF/VI/UMEC was associated with a significantly higher risk of COPD exacerbations (5.6% vs. 3.9%; RR 1.44; 95% CI 1.30–1.59; p < 0.001) and ARF (2.5% vs. 1.9%; RR 1.28; 95% CI 1.11–1.46; p < 0.001) compared with BUD/GLY/FOR. Time-to-event analyses demonstrated lower event-free probability for exacerbations (HR 1.35; (95% CI 1.21–1.50) and ARF (HR 1.15; (95% CI 1.00–1.32))). All-cause mortality was numerically higher in the FF/VI/UMEC cohort (5.2% vs. 4.7%; RR 1.09; 95% CI 1.00–1.19; p = 0.050); however, time-to-event analysis did not demonstrate a statistically significant difference. Hospitalization rates were similar between groups. Conclusions: In this large propensity score-matched real-world cohort study, patients receiving BUD/GLY/FOR experienced lower rates of COPD exacerbations and acute respiratory failure than those receiving FF/VI/UMEC. Because of the retrospective observational nature of the analysis, these findings should be considered hypothesis-generating and require confirmation in prospective comparative effectiveness studies.

Abstract Introduction: Chronic Obstructive Pulmonary Disease (COPD) exacerbations increase inflammation, immobilization, and thrombotic risk, leading to a higher incidence of pulmonary embolism (PE). This study evaluates the incidence and risk of PE in patients with acute exacerbations of COPD (AECOPD) compared to those without exacerbations. Methodology: This retrospective cohort study utilized data from 94 healthcare organizations, identifying two cohorts: patients with AECOPD and those without exacerbations. Inclusion was based on ICD-10-CM codes, and individuals with malignancies, coagulation disorders, or prior PE were excluded. Propensity score matching was performed to balance the cohorts on demographics, clinical characteristics, and medications. The primary outcome was PE incidence, analyzed using risk differences, risk ratios, odds ratios, and Kaplan-Meier survival analysis to evaluate mortality outcomes associated with PE. Results: After matching, both cohorts comprised 174,345 patients each. The mean age was approximately 73 years, with a slight female predominance (49.0% in AECOPD vs. 49.3% in non-AECOPD). The incidence of PE was significantly higher in the AECOPD cohort (15%) compared to the non-AECOPD cohort (8%) (p &lt; 0.001). Specifically, 2,162 patients (1.3%) in the AECOPD cohort developed PE, compared to 1,467 patients (0.9%) in the non-AECOPD cohort. The risk difference was 0.004 (95% CI: 0.003, 0.005; p &lt; 0.001). The risk ratio for PE in the AECOPD cohort was 1.477 (95% CI: 1.382, 1.577), and the odds ratio was 1.483 (95% CI: 1.387, 1.585). Survival analysis revealed a probability of 95.23% in the AECOPD cohort and 97.15% in the non-AECOPD cohort, with significant differences (χ² = 153.746, df = 1, p &lt; 0.001). The hazard ratio for mortality associated with PE was 1.517 (95% CI: 1.419, 1.621). Conclusion: Patients with AECOPD have a significantly higher incidence of pulmonary embolism compared to those without exacerbations. PE is often overlooked in AECOPD patients due to the overlap in clinical symptoms, making timely diagnosis and treatment challenging. This can result in delayed management and poor outcomes. Therefore, it is crucial to enhance understanding of the clinical manifestations, diagnosis, and treatment of COPD complicated by PE to improve diagnostic accuracy, ensure timely intervention, and optimize patient prognosis.

Abstract Introduction: Chronic obstructive pulmonary disease (COPD) represents a significant global health challenge, particularly in its moderate to severe cases, where effective management is crucial to improving patient outcomes. The integration of inhaled corticosteroids with long-acting β2-adrenoceptor agonists and long-acting muscarinic antagonists in fixed-dose combinations has emerged as a cornerstone of therapy. This study evaluates the efficacy of two triple therapy regimens — Glycopyrrolate, Budesonide, and Formoterol Fumarate (GLY/BUD/FOR) and Fluticasone Furoate, Vilanterol, and Umeclidinium (FF/VI/UMEC) —in adults aged 45 and older with diagnosed COPD with FEV1/FVC &lt; 70% to assess the impact of these regimens on the preventing COPD exacerbations and acute hypoxemic respiratory failure. Methods: A retrospective cohort analysis was conducted using the TriNetX database. Patients with moderate to severe COPD and FEV1/FVC &lt; 70% were identified based on ICD codes, and two cohorts were formed based on the prescribed inhaler therapy: GLY/BUD/FOR and FF/VI/UMEC. Patients with comorbid asthma, heart failure, or pneumonia were excluded. A 1:1 propensity-score matching (PSM) analysis was performed to balance covariates such as age, gender, smoking status, and baseline lung function to minimize confounding and bias. Post-matching, both had 16,052 patients. Ultimately, 23,331 patients (FF/VI/UMEC: 11,234, GLY/BUD/FOR: 12,097) with a mean age of 67.4 ± 10.1 years and 55.3% males were included. Results: Among groups, 10.4% of patients on FF/VI/UMEC experienced COPD exacerbations compared to 6.7% on GLY/BUD/FOR (Risk Ratio: 1.55, 95% CI: 1.42-1.69, p &lt; 0.001). Kaplan-Meier analysis showed a lower survival probability in the FF/VI/UMEC group (77.7% vs. 83.9%, p &lt; 0.001). For acute respiratory failure, 3.5% of patients on FF/VI/UMEC experienced this outcome compared to 2.8% on GLY/BUD/FOR (Risk Ratio: 1.28, 95% CI: 1.12-1.45, p = 0.003). Conclusion: Our study suggests that FF/VI/UMEC demonstrated an increased risk of COPD exacerbations and acute hypoxic respiratory failure compared to the group receiving GLY/BUD/FOR. This indicates that GLY/BUD/FOR may provide enhanced protective benefits in patients with moderate to severe COPD, improving disease management and minimizing healthcare resource utilization. Further studies are warranted to explore the long-term benefits and potential mechanisms underlying the observed differences.

Abstract Background: Pulmonary rehabilitation (PR) is a comprehensive intervention and essential component for integrated care with patients with chronic respiratory diseases, especially Chronic Obstructive Pulmonary Disease (COPD). American Thoracic Society (ATS) strongly recommends PR for patients with COPD after exacerbation. PR has been shown to reduce mortality, improve quality of life, and decrease hospital readmissions in patients with COPD. Despite these benefits, access to PR remains unevenly distributed, particularly among racial and ethnic minorities. This study explores racial and ethnic disparities in PR utilization among COPD patients with a history of exacerbations. Methods: Utilizing data from the TrinetX Research Network, we examined two cohorts of COPD patients. Cohort 1 (N=493) consisted of patients with COPD and prior exacerbations who received PR, while Cohort 2 (N=457,573) included similar patients who did not receive PR. Demographics, specifically, race and ethnicity, were statistically analyzed to assess the presence and significance of disparities, using chi-square tests and standardized mean differences (SMD) to provide a comparative framework.Results:493 patients were in the PR group and 457,573 patients in the non-PR group, comprising 458,066 patients across both cohorts. Among the 493 patients in the PR cohort, the largest group was categorized as Other Race (192 patients, 38.9%, p &lt; 0.001, SMD = 1.040), followed by White patients (154 patients, 31.2%, p &lt; 0.001, SMD = 0.899). Black or African American and Asian patients were both minimally represented, with 10 patients each (2.0%, p &lt; 0.001, SMD = 0.319 and SMD = 0.034, respectively), while 137 patients (27.8%, p &lt; 0.001, SMD = 0.349) were of Unknown Race. In contrast, the non-PR cohort, comprising 470,239 patients, had a substantially higher proportion of White patients (330,409 patients, 72.2%) and a significantly greater representation of Black or African American individuals (42,573 patients, 9.3%, p &lt; 0.001, SMD = 0.319) and Hispanic or Latino individuals (13,709 patients, 3.0%, p &lt; 0.001, SMD = 0.249) compared to the PR cohort. Conclusion: This study highlights significant disparities in the utilization of PR among COPD patients, with underrepresented racial and ethnic groups demonstrating lower access to this intervention. These findings highlight the need for targeted strategies to address potential barriers to PR, promoting equitable access across diverse populations. Further investigation into structural and socioeconomic factors influencing PR access will be crucial to fostering inclusive care and reducing healthcare disparities in COPD management.

Abstract Introduction: Obesity's increasing prevalence significantly impacts Intensive Care Unit (ICU) patient outcomes, especially for those requiring prolonged mechanical ventilation. This study investigates the effect of Body Mass Index (BMI) on mortality and complications—such as acute respiratory distress syndrome (ARDS), pulmonary embolism (PE), and deep vein thrombosis (DVT)—in ICU patients intubated for over 96 hours. Methods: We conducted a retrospective cohort study using the TriNetX database to identify patient populations with relevant ICD codes. Patients who had received anticoagulation and had been on mechanical ventilation for more than 96 hours were included. Cohort 1 consisted of patients with a BMI of 30-44.9 kg/m² (n = 70,379), and Cohort 2 included patients with a BMI of 18.5-29.9 kg/m² (n = 111,054). Both cohorts were matched using propensity score matching (PSM), resulting in balanced groups of 47,233 patients. The mean age was 64.3 ± 15.1 years in Cohort 1 and 64.5 ± 16.5 years in Cohort 2, with a male predominance of 57.9% in both cohorts after matching. Outcomes (mortality, PE, DVT, and ARDS) were identified using ICD-10 codes and analyzed on Days 14, 30, and 90. Results: Higher BMI was associated with increased all-cause mortality across all measured time points. By Day 14, mortality was 23.0% in Cohort 1 versus 19.2% in Cohort 2 (RiskRatio [RR]: 1.196; 95% CI: 1.166-1.226). By Day 90, mortality reached 37.6% in Cohort 1 compared to 32.6% in Cohort 2 (RR: 1.151; 95% CI: 1.132-1.171). Additionally, the risk of developing ARDS was higher in Cohort 1, with statistically significant risk ratios observed on Day 14 (RR: 1.117; 95% CI: 1.020-1.222) and Day 30 (RR: 1.094; 95%CI: 1.010-1.186). PE risk in Cohort 1 significantly increased by Day 30 (RR: 1.119; 95% CI: 1.008-1.243), while DVT risk was also elevated in Cohort 1 at both Day 14 (RR:1.140; 95% CI: 1.037-1.253) and Day 30 (RR: 1.129; 95% CI: 1.040-1.224). Conclusion: Higher BMI in mechanically ventilated ICU patients intubated for more than 96 hours is associated with increased mortality and a higher incidence of complications, including ARDS, PE, and DVT. This study contributes to our understanding of BMI's impact on ICU outcomes, highlighting critical areas for improved clinical management in this population and the need for targeted interventions in obese ICU patients, such as optimized respiratory support and monitoring for thromboemboliccomplications.

Abstract Importance: Severe gender gap in academic research output is pervasive across all medical specialties, including hematology and oncology. Objective: This bibliometric study aimed to investigate the representation of females in premier first and last authorship positions of hematology- and oncology-related randomized controlled trials (RCTs) published between 2000–2022. Additionally, we investigated the trend of females in first authorship positions with a male or female senior author. Design: Bibliometric analysis of clinically oriented hematology and oncology RCTs published between 2000 and 2022 across all PubMed-indexed journals. Participants: First and last authors of 5,891 hematology- and oncology-related RCTs. Main Outcomes: Change in the proportion of female first and senior authors and the proportion of RCTs with the same and cross-gender dyads of first and senior authors. Results: 5,891 RCTs were available with identifiable gender of first and senior authors. A total of 49 countries and 62 journals were represented in our study sample. The proportion of females in our study population was 22.9% (n = 1,349) in the first authorship and 17.5% (n = 1,032) in the senior authorship positions and were predominantly affiliated with institutions in high-income countries (94.1%, n = 1,270 and 95.3%, n = 984). We also noted a significant upward trend in the percentage of female authors in the first authorship position (16.3% in 2000 to 32.4% in 2022, p = 0.001) between 2000 and 2022; the trend was stronger with male than female senior authors. However, the odds of the females in the first authorship position with a female senior author were significantly higher only when both authors came from high-income countries [OR = 1.702 (95%CI 1.461–1.984; p < 0.0001]. The proportion of female senior authors remained stable during the study period. Conclusions and Relevance: Despite early trends in closing the gender gap in the authorship of hematology- and oncology-related RCTs, females remain severely underrepresented in premier authorship positions. The increasing proportion of female authors in the first authorship position with a male senior author indicated that a more inclusive effort to train, mentor, and encourage young female physician-scientists with the involvement of senior male and female researchers will likely accelerate the overall increase in female authorship.