Aksamit, Timothy R.

Abstract Rationale Nontuberculous mycobacteria (NTM) are prevalent among patients with bronchiectasis. However, the long-term natural history of patients with NTM and bronchiectasis is not well described. Objectives To assess the impact of NTM on 5-year clinical outcomes and mortality in patients with bronchiectasis. Methods Patients in the Bronchiectasis and NTM Research Registry with ⩾5 years of follow-up were eligible. Data were collected for all-cause mortality, lung function, exacerbations, hospitalizations, and disease severity. Outcomes were compared between patients with and without NTM at baseline. Mortality was assessed using Cox proportional hazards models and the log-rank test. Measurements and Main Results In total, 2,634 patients were included: 1,549 (58.8%) with and 1,085 (41.2%) without NTM at baseline. All-cause mortality (95% confidence interval) at Year 5 was 12.1% (10.5%, 13.7%) overall, 12.6% (10.5%, 14.8%) in patients with NTM, and 11.5% (9.0%, 13.9%) in patients without NTM. Independent predictors of 5-year mortality were baseline FEV1 percent predicted, age, hospitalization within 2 years before baseline, body mass index, and sex (all P < 0.01). The probabilities of acquiring NTM or Pseudomonas aeruginosa were approximately 4% and 3% per year, respectively. Spirometry, exacerbations, and hospitalizations were similar, regardless of NTM status, except that annual exacerbations were lower in patients with NTM (P < 0.05). Conclusions Outcomes, including exacerbations, hospitalizations, rate of loss of lung function, and mortality rate, were similar across 5 years in patients with bronchiectasis with or without NTM.

Abstract Introduction Bronchiectasis (BE) is characterized by recurrent infections and dilated airways and has been associated with recurrent exacerbations and hospitalizations affecting quality of life. Approximately 40-60% of patients with BE have concomitant OSA, with an increased AHI (apnea-hypopnea index) in BE patients with Pseudomonas infections. We hypothesize that patients with BE are less tolerant of PAP therapies, contributing to worsening quality of life related to either condition. We aim to determine differences in PAP adherence and treatment response in patients with BE and OSA compared with a matched OSA-control group. Methods A retrospective cohort analysis was conducted on adult patients evaluated at Mayo Clinic Center for Sleep Medicine between January 2000 to December 2020. Inclusion criteria were patients greater than 18 years old diagnosed with BE and OSA per current guidelines and were prescribed PAP therapy. Control OSA patients were matched to BE/OSA patients by gender, BMI, and AHI severity. Exclusion criteria included cystic fibrosis, hospice enrollment, active lung transplant evaluation, and lack of sleep clinic follow-up. Follow-up visits determined PAP compliance and change in quality-of-life metrics over 3 years. Results We compared 50 patients with BE/OSA with 74 OSA matched controls. The etiology of BE in these cases included COPD (32%) or other etiologies (34%). Baseline characteristics were not statistically different in gender, BMI, and AHI severity across groups. Median treatment follow-up for the BE/OSA group was 3 years [IQR 2 to 4]. Importantly, there was no statistically significant difference in PAP adherence in patients with BE/OSA compared to OSA controls regardless of etiology of BE, but these patients more often required supplemental oxygen therapy. Interestingly, there was a statistically significant increase in MRC and decrease in FEV1 over time in BE patients compliant to therapy. Conclusion There was no significant difference in baseline OSA characteristics, treatment response, and PAP adherence, except for need of oxygen supplementation in BE patients with OSA compared with matched non-BE OSA controls. FEV1 values decreased, and dyspnea score increased in BE patients compliant to PAP therapy; however, future larger studies should include longer-term follow-up to further assess the impact of PAP therapy on BE progression and outcomes. Support (if any)

Abstract Background Nontuberculous mycobacterial pulmonary disease (NTMPD) is a chronic lung infection that is challenging to treat, especially refractory NTMPD. Data are limited on the natural history, risk profile, and burden of refractory NTMPD. The objective of this study was to evaluate the burden of illness (BOI) among patients with NTMPD who later develop refractory NTMPD vs those who do not. Methods This was a retrospective analysis using BRR data. Patients treated for NTMPD were included and stratified as refractory (received oral clofazimine/bedaquiline or inhaled amikacin/ALIS, or remained sputum culture positive despite ≥ 6 months of treatment) or nonrefractory. Modified bronchiectasis severity index (mBSI) at baseline visit and BOI including comorbid conditions and surgeries at the treatment visit were compared by cross-sectional analysis between the two groups. Longitudinal analysis of BOI focused on exacerbations and hospitalizations in the refractory group at their pre-refractory visit and refractory visit (first visit meeting the refractory definition). Results A total of 1,064 patients treated for NTMPD were included: 462 (43.4%) refractory and 602 (56.6%) nonrefractory. During the baseline period, the refractory group had more severe bronchiectasis (Table 1, mBSI, mean [SD], 7.3 [3.4] vs 6.7 [3.4]). At the time of treatment, bronchiectasis was more common in the refractory than nonrefractory (96.2% vs 89.7%) group, as were hemoptysis (26.6% vs 16.3%) and GERD (50.5% vs 39.9%). Except BMI, there were no statistically significant differences between the pre-refractory and nonrefractory treatment visits (Table 2). In the refractory group, exacerbations and hospitalizations remained high from the pre-refractory to refractory visit (45.6% vs 39.4% and 13.3% vs 12.8%, respectively). Oxygen and bronchial hygiene use increased from the pre-refractory to the refractory visit (5.2% vs 9.3% and 54.5% vs 61.7%, respectively) consistent with increased management of respiratory conditions when not responding to treatment (Table 2). Conclusion Refractory NTMPD imposes a high disease burden on patients in the BRR. This high burden was present at pre-refractory visits and through the development of refractory status. Disclosures Timothy R. Aksamit, MD, AstraZeneca: Advisor/Consultant|Baxter International, Hill-Rom: Advisor/Consultant|Insmed Incorporated: Advisor/Consultant|Johnson & Johnson: Advisor/Consultant|Redhill Biopharma: Advisor/Consultant|RespirTech: Advisor/Consultant|Spero Therapeutics: Advisor/Consultant|Zambon: Advisor/Consultant David M. Mannino, MD, AstraZeneca: Advisor/Consultant|GlaxoSmithKline: Advisor/Consultant|Up to Date: Advisor/Consultant Ping Wang, PhD, Insmed Incorporated: Salary|Insmed Incorporated: Stocks/Bonds Mariam Hassan, PhD, B. Pharm, Insmed Incorporated: Salary|Insmed Incorporated: Stocks/Bonds

Abstract Among 1038 participants with pulmonary Mycobacterium avium complex and 120 with Mycobacterium abscessus enrolled in the US Bronchiectasis and NTM Research Registry, less than half received antibiotic therapy in the 24 months before registry enrollment, of which less than half were guideline based. Adverse effects occurred in 21% of therapy recipients, of whom 33% discontinued therapy.

Background and objectives: Little is known about outcome improvements and disparities in cardiac arrest and active cancer. We performed the first known AI and propensity score (PS)-augmented clinical, cost-effectiveness, and computational ethical analysis of cardio-oncology cardiac arrests including left heart catheterization (LHC)-related mortality reduction and related disparities. Materials and methods: A nationally representative cohort analysis was performed for mortality and cost by active cancer using the largest United States all-payer inpatient dataset, the National Inpatient Sample, from 2016 to 2018, using deep learning and machine learning augmented propensity score-adjusted (ML-PS) multivariable regression which informed cost-effectiveness and ethical analyses. The Cardiac Arrest Cardio-Oncology Score (CACOS) was then created for the above population and validated. The results informed the computational ethical analysis to determine ethical and related policy recommendations. Results: Of the 101,521,656 hospitalizations, 6,656,883 (6.56%) suffered cardiac arrest of whom 61,300 (0.92%) had active cancer. Patients with versus without active cancer were significantly less likely to receive an inpatient LHC (7.42% versus 20.79%, p < 0.001). In ML-PS regression in active cancer, post-arrest LHC significantly reduced mortality (OR 0.18, 95%CI 0.14–0.24, p < 0.001) which PS matching confirmed by up to 42.87% (95%CI 35.56–50.18, p < 0.001). The CACOS model included the predictors of no inpatient LHC, PEA initial rhythm, metastatic malignancy, and high-risk malignancy (leukemia, pancreas, liver, biliary, and lung). Cost-benefit analysis indicated 292 racial minorities and $2.16 billion could be saved annually by reducing racial disparities in LHC. Ethical analysis indicated the convergent consensus across diverse belief systems that such disparities should be eliminated to optimize just and equitable outcomes. Conclusions: This AI-guided empirical and ethical analysis provides a novel demonstration of LHC mortality reductions in cardio-oncology cardiac arrest and related disparities, along with an innovative predictive model that can be integrated within the digital ecosystem of modern healthcare systems to improve equitable clinical and public health outcomes.