Insights from Application of a Hierarchical Spatio-Temporal Model to an Intensive Urban Black Carbon Monitoring Dataset.

Existing regulatory pollutant monitoring networks rely on a small number of centrally located measurement sites that are purposefully sited away from major emission sources. While informative of general air quality trends regionally, these networks often do not fully capture the local variability of air pollution exposure within a community. Recent technological advancements have reduced the cost of sensors, allowing air quality monitoring campaigns with high spatial resolution. The 100×100 black carbon (BC) monitoring network deployed 100 low-cost BC sensors across the 15 km2 West Oakland, CA community for 100 days in the summer of 2017, producing a nearly continuous site-specific time series of BC concentrations which we aggregated to one-hour averages. Leveraging this dataset, we employed a hierarchical spatio-temporal model to accurately predict local spatio-temporal concentration patterns throughout West Oakland, at locations without monitors (average cross-validated hourly temporal R 2=0.60). Using our model, we identified spatially varying temporal pollution patterns associated with small-scale geographic features and proximity to local sources. In a sub-sampling analysis, we demonstrated that fine scale predictions of nearly comparable accuracy can be obtained with our modeling approach by using ~30% of the 100×100 BC network supplemented by a shorter-term high-density campaign.

Protocol for a pragmatic trial testing a self-directed lifestyle program targeting weight loss among patients with obstructive sleep apnea (POWER Trial).

BACKGROUND: Obesity comprises the single greatest reversible risk factor for obstructive sleep apnea (OSA). Despite the potential of lifestyle-based weight loss services to improve OSA severity and symptoms, these programs have limited reach. POWER is a pragmatic trial of a remote self-directed weight loss care among patients with OSA. METHODS: POWER randomizes 696 patients with obesity (BMI 30-45 kg/m2) and recent diagnosis or re-confirmation of OSA 1:1 to either a self-directed weight loss intervention or usual care. POWER tests whether such an intervention improves co-primary outcomes of weight and sleep-related quality of life at 12 months. Secondary outcomes include sleep symptoms, global ratings of change, and cardiovascular risk scores. Finally, consistent with a hybrid type 1 approach, the trial embeds an implementation process evaluation. We will use quantitative and qualitative methods including budget impact analyses and qualitative interviews to assess barriers to implementation. CONCLUSIONS: The results of POWER will inform population health approaches to the delivery of weight loss care. A remote self-directed program has the potential to be disseminated widely with limited health system resources and likely low-cost.

Lifestyle Intervention and Excess Weight in Chronic Obstructive Pulmonary Disease (COPD): INSIGHT COPD Randomized Clinical Trial.

Rationale: Being overweight or obese is common among patients with chronic obstructive pulmonary disease (COPD), but whether interventions targeted at weight loss improve functional impairments is unknown. Objectives: INSIGHT (Intervention Study in Overweight Patients with COPD) tested whether a pragmatic low-intensity lifestyle intervention would lead to better physical functional status among overweight or obese participants with COPD. Methods: The trial was a 12-month, multicenter, patient-level pragmatic clinical trial. Participants were recruited from April 2017 to August 2019 from 38 sites across the United States and randomized to receive usual care or usual care plus lifestyle intervention. The intervention was a self-directed video program delivering the Diabetes Prevention Program's Group Lifestyle Balance curriculum. Results: The primary outcome was 6-minute-walk test distance at 12 months. Priority secondary outcomes were postwalk modified Borg dyspnea at 12 months and weight at 12 months. Participants (N = 684; mean age, 67.0 ± 8.0 yr [standard deviation]; 41.2% female) on average were obese (body mass index, 33.0 ± 4.6 kg/m2) with moderate COPD (forced expiratory volume in 1 second % predicted, 58.1 ± 15.7%). At 12 months, participants randomized to the intervention arm walked farther (adjusted difference, 42.3 ft [95% confidence interval (CI), 7.9-76.7 ft]; P = 0.02), had less dyspnea at the end of the 6-minute-walk test (adjusted difference, -0.36 [95% CI, -0.63 to -0.09]; P = 0.008), and had greater weight loss (adjusted difference, -1.34 kg [95% CI, -2.33 to -0.34 kg]; P = 0.008) than control participants. The intervention did not improve the odds of achieving clinically meaningful thresholds of walk distance (98.4 ft) or dyspnea (1 unit) but did achieve meaningful thresholds of weight loss (3% and 5%). Conclusions: Among participants with COPD who were overweight or obese, a self-guided low-intensity video-based lifestyle intervention led to modest weight loss but did not lead to clinically important improvements in physical functional status and dyspnea. Clinical trial registered with www.clinicaltrials.gov (NCT02634268).

Use of elexacaftor/tezacaftor/ivacaftor among cystic fibrosis lung transplant recipients.

BACKGROUND: Cystic fibrosis (CF) lung transplant (LT) recipients may warrant treatment with elexacaftor/tezacaftor/ivacaftor (ETI) to improve extrapulmonary manifestations of CF. Our objectives were to identify reasons for prescribing ETI after LT and evaluate changes in body mass index (BMI), hemoglobin A1c, hemoglobin, and liver enzymes. METHODS: This was an electronic health record-based cohort study, October 2019-September 2020, at 14 CF LT Consortium sites in North America. The study included CF LT recipients prescribed ETI after transplant. Differences in BMI, A1c, and hemoglobin were assessed with paired t-tests. RESULTS: There were 94 patients prescribed ETI; indications included sinus disease (68%), GI symptoms (39%), or low BMI (19%). Prescriptions were written by CF physicians (34%), LT physicians (27%), or physicians who practice both CF and LT (39%). Forty patients (42%) stopped ETI at a median of 56 days [IQR 26, 139] after start/prescription date. ETI was not associated with a significant change in BMI (0.2 kg/m2, 95% CI [-0.1, 0.6], p = 0.150), but was associated with decreased A1c (0.4%, 95% CI 0.2, 0.7, p = 0.003), and increased hemoglobin for patients with anemia (0.6 g/dL, 95% CI 0.2, 1.0, p = 0.007). Three people (3%) stopped ETI due to elevated transaminases. CONCLUSIONS: ETI is rarely prescribed for non-pulmonary indications after LT for CF. Further study is needed to determine the risks and benefits of ETI in the CF lung transplant population given the potential for drug interactions, side effects leading to discontinuation of ETI, and the possible mechanisms for ETI to positively impact long-term post-transplant outcomes.

Validation of the French 3-year prognostic score for death or lung transplant in the United States cystic fibrosis population.

In 2017, Nkam et al. published a prognostic score to predict death or lung transplant within 3 years among adult cystic fibrosis (CF) patients. Their model was developed using French CF registry data and was subsequently validated in the Canadian CF registry. We evaluated this prognostic score using data from adult patients with CF in the United States (US) CF Foundation Patient registry, combined with lung transplant records from the United Network for Organ Sharing (UNOS) Registry (2013 to 2016) (n=11,542). We found that the prognostic score had a very good discriminative index predicting death or lung transplant in the US CF population (AUC 0.88, 95% CI 0.88-0.89) with an odds ratio (OR) of 2.83 (95% CI 2.69 - 2.97) for each unit increase in the score. However, it did not provide significant additional utility over an FEV1 ≤30% of predicted as a predictor of death or lung transplant.

Variability in azithromycin practices among lung transplant providers in the International Society for Heart and Lung Transplantation Community.

Chronic lung allograft dysfunction (CLAD) is the most important long-term complication after lung transplant (LTx), and clinical experience suggests significant variability in its management. We sought to capture azithromycin practices among LTx providers internationally. A survey was distributed via the International Society for Heart and Lung Transplantation and completed by 103 respondents (15 countries). Azithromycin indications, timing, and dosing varied significantly, and 37 (36%) reported inconsistency even within their center. Thirty (29%) reported initiating azithromycin prophylactically (during initial transplant hospitalization). Of 73 others, only 10 (14%) reported waiting until CLAD diagnosis (with persistent ≥20% pulmonary function decline). Most initiated azithromycin after a CLAD risk-factor and/or event, including 59 (81%) for a persistent ≥10% decrement in FEV1, 32 (44%) for lymphocytic bronchiolitis, and 27 (37%) for bronchoalveolar lavage neutrophilia. Azithromycin prescribing patterns appear to vary significantly, and further study is needed to elucidate the optimal timing and indications for its initiation after LTx.

A multi-institutional review of outcomes in biopsy-proven acute invasive fungal sinusitis.

BACKGROUND: Acute invasive fungal sinusitis (AIFS) is a rare, aggressive infection occurring in immunocompromised patients. In this study we examined factors that affect survival in AIFS, and whether immune-stimulating therapies (IST) improve survival. METHODS: Pathology records of biopsy-proven AIFS were reviewed from 3 academic institutions from 1995 to 2016. Univariate and multivariate Cox regressions were performed at 1 and 3 months from diagnosis. RESULTS: One hundred fourteen patients were included; 45 received IST. In the univariate analysis, the following factors were associated with worse survival: hematologic malignancy (3-month hazard ratio [HR], 3.7; p = 0.01); recent chemotherapy (within 1 month of AIFS diagnosis) (3-month HR, 2.3; p = 0.02); recent bone marrow transplant (BMT) (3-month HR, 2.5; p = 0.02); and infection with atypical fungi (1-month HR, 3.1; p = 0.04). The following were associated with improved survival in univariate analysis: increasing A1c% (1-month HR, 0.7; p = 0.01) and surgical debridement (1-month HR, 0.1; p = 0.001). One third of patients with a hematologic malignancy had an absolute neutrophil count (ANC) >1000 at the time of diagnosis. ANC was not associated with prognosis in these patients. The following were associated with worse survival in multivariate analyses: hematologic malignancy; recent chemotherapy; atypical organisms; and cavernous sinus extension. In multivariate analyses, IST was associated with a 70% reduction in mortality at 1 month (p = 0.02). CONCLUSION: We presented the largest series of AIFS. Further studies are needed to examine the importance of ANC in diagnosis and prognosis. Patients diagnosed with atypical organisms may be at higher risk of death. IST likely improves short-term survival, but prospective studies are needed.