Health System Approach to Improve Chronic Obstructive Pulmonary Disease Care after Hospital Discharge: Stepped-Wedge Clinical Trial.

Rationale: Patients discharged from the hospital for chronic obstructive pulmonary disease (COPD) exacerbation have impaired quality of life and frequent readmission and death. Clinical trials to reduce readmission demonstrate inconsistent results, including some demonstrating potential harms. Objectives: We tested whether a pragmatic proactive interdisciplinary and virtual review of patients discharged after hospitalization for COPD exacerbation would improve quality of life, using the Clinical COPD Questionnaire, and reduce all-cause 180-day readmission and/or mortality. Methods: We performed a stepped-wedge clinical trial. We enrolled primary care providers and their patients after hospital discharge for COPD at two Department of Veterans Affairs medical centers and 10 outpatient clinics. A multidisciplinary team reviewed health records and developed treatment recommendations delivered to primary care providers via E-consult. We facilitated uptake by entering recommendations as unsigned orders that could be accepted, modified, or canceled. Providers and patients made all final treatment decisions. Measurements and Main Results: We enrolled 365 primary care providers. Over a 30-month period, 352 patients met eligibility criteria, with 191 (54.3%) patients participating in the control and 161 (45.7%) in the intervention. The intervention led to clinically significant better Clinical COPD Questionnaire scores (-0.47; 95% confidence interval [CI], -0.85 to -0.09; 52.6% missing) but did not reduce 180-day readmission and/or mortality (adjusted odds ratio, 0.83; 95% CI, 0.49 to 1.38), in part because of wide CIs. Among the 161 patients in the intervention group, we entered 519 recommendations as unsigned orders, of which 401 (77.3%) were endorsed. Conclusions: A pragmatic health system-level intervention that delivered proactive specialty supported care improved quality of life but did not reduce 180-day readmission or death. Clinical trial registered with www.clinicaltrials.gov (NCT02021955).

STAT6 deficiency ameliorates severity of oxazolone colitis by decreasing expression of claudin-2 and Th2-inducing cytokines.

Patients suffering from ulcerative colitis (UC) exhibit chronic colonic inflammation caused by a dysregulated mucosal immune response and epithelial barrier disruption. Th2 cytokines, including IL-13, have been implicated in the pathogenesis of UC. IL-13 induces phosphorylation of STAT6, and we previously demonstrated increased epithelial p-STAT6 in children with UC. In this study, we investigated the role of STAT6 in oxazolone colitis, a murine model of UC, by inducing colitis in STAT6-deficient (STAT6(-/-)) and wild type (WT) mice. We observed increased epithelial cell, T cell, macrophage, and NKT cell STAT6 phosphorylation, as well as increased p-STAT6(+) IL-13-producing NKT cells, in colitic WT mice. Colitis was attenuated in STAT6(-/-) mice, with improvements in weight, colon length, and histopathology. There was decreased induction of the pore-forming tight junction protein claudin-2 in STAT6(-/-) mice. Similarly, short hairpin RNA STAT6 knockdown reduced claudin-2 induction and transepithelial resistance decrease in IL-13-treated human T84 cells. Tissue expression of IL-13, IFN-γ, IL-17, and IL-10 mRNA was similarly induced in WT and STAT6(-/-) colitic mice; however, we observed increased mRNA expression for the Th2-inducing cytokines IL-33 and thymic stromal lymphopoietin in WT mice with colitis, which was abrogated in STAT6(-/-) mice. Mesenteric lymph node cells from STAT6(-/-) mice with colitis exhibited reduced secretion of IL-4, IL-5, IL-13, and IFN-γ. IL-33 augmented mesenteric lymph node cell secretion of IL-5, IL-13, IL-6, and IFN-γ. These data implicate STAT6 in the pathogenesis of colitis in vivo with important roles in altering epithelial barrier function and regulating Th2-inducing cytokine production.

Measuring Patient-Reported Use and Outcomes From Complementary and Integrative Health Therapies: Development of the Complementary and Integrative Health Therapy Patient Experience Survey.

Background: Assessing the use and effectiveness of complementary and integrative health (CIH) therapies via survey can be complicated given CIH therapies are used in various locations and formats, the dosing required to have an effect is unclear, the potential health and well-being outcomes are many, and describing CIH therapies can be challenging. Few surveys assessing CIH therapy use and effectiveness exist, and none sufficiently reflect these complexities. Objective: In a large-scale Veterans Health Administration (VA) quality improvement effort, we developed the "Complementary and Integrative Health Therapy Patient Experience Survey", a longitudinal, electronic patient self-administered survey to comprehensively assess CIH therapy use and outcomes. Methods: We obtained guidance from the literature, subject matter experts, and Veteran patients who used CIH therapies in designing the survey. As a validity check, we completed cognitive testing and interviews with those patients. We conducted the survey (March 2021-April 2023), inviting 15,608 Veterans with chronic musculoskeletal pain with a recent CIH appointment or referral identified in VA electronic medical records (EMR) to participate. As a second validity check, we compared VA EMR data and patient self-reports of CIH therapy utilization a month after survey initiation and again at survey conclusion. Results: The 64-item, electronic survey assesses CIH dosing (amount and timing), delivery format and location, provider location, and payor. It also assesses 7 patient-reported outcomes (pain, global mental health, global physical health, depression, quality of life, stress, and meaning/purpose in life), and 3 potential mediators (perceived health competency, healthcare engagement, and self-efficacy for managing diseases). The survey took 17 minutes on average to complete and had a baseline response rate of 45.3%. We found high degrees of concordance between self-reported and EMR data for all therapies except meditation. Conclusions: Validly assessing patient-reported CIH therapy use and outcomes is complex, but possible.

Association of Guideline-Recommended COPD Inhaler Regimens With Mortality, Respiratory Exacerbations, and Quality of Life: A Secondary Analysis of the Long-Term Oxygen Treatment Trial.

BACKGROUND: Although inhaled therapy reduces exacerbations among patients with COPD, the effectiveness of providing inhaled treatment per risk stratification models remains unclear. RESEARCH QUESTION: Are inhaled regimens that align with the 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy associated with clinically important outcomes? STUDY DESIGN AND METHODS: We conducted secondary analyses of Long-term Oxygen Treatment Trial (LOTT) data. The trial enrolled patients with COPD with moderate resting or exertional hypoxemia between 2009 and 2015. Our exposure was the patient-reported inhaled regimen at enrollment, categorized as either aligning with, undertreating, or potentially overtreating per the 2017 GOLD strategy. Our primary composite outcome was time to death or first hospitalization for COPD. Additional outcomes included individual components of the composite outcome and time to first exacerbation. We generated multivariable Cox proportional hazard models across strata of GOLD-predicted exacerbation risk (high vs low) to estimate between-group hazard ratios for time to event outcomes. We adjusted models a priori for potential confounders, clustered by site. RESULTS: The trial enrolled 738 patients (73.4% men; mean age, 68.8 years). Of the patients, 571 (77.4%) were low risk for future exacerbations. Of the patients, 233 (31.6%) reported regimens aligning with GOLD recommendations; most regimens (54.1%) potentially overtreated. During a 2.3-year median follow-up, 332 patients (44.9%) experienced the composite outcome. We found no difference in time to composite outcome or death among patients reporting regimens aligning with recommendations compared with undertreated patients. Among patients at low risk, potential overtreatment was associated with higher exacerbation risk (hazard ratio, 1.42; 95% CI, 1.09-1.87), whereas inhaled corticosteroid treatment was associated with 64% higher risk of pneumonia (incidence rate ratio, 1.64; 95% CI, 1.01-2.66). INTERPRETATION: Among patients with COPD with moderate hypoxemia, we found no difference in clinical outcomes between inhaled regimens aligning with the 2017 GOLD strategy compared with those that were undertreated. These findings suggest the need to reevaluate the effectiveness of risk stratification model-based inhaled treatment strategies.

Progression of Unilateral Hearing Loss in Children With and Without Ipsilateral Cochlear Nerve Canal Stenosis: A Hazard Analysis.

OBJECTIVE: To investigate the risk of hearing loss progression in each ear among children with unilateral hearing loss associated with ipsilateral bony cochlear nerve canal (BCNC) stenosis. SETTING: Tertiary pediatric referral center. PATIENTS: Children diagnosed with unilateral hearing loss who had undergone temporal bone computed tomography imaging and had at least 6 months of follow-up audiometric testing were identified from a prospective audiological database. INTERVENTIONS: Two pediatric radiologists blinded to affected ear evaluated imaging for temporal bone anomalies and measured bony cochlear canal width independently. All available audiograms were reviewed, and air conduction thresholds were documented. MAIN OUTCOME MEASURE: Progression of hearing loss was defined by a 10 dB increase in air conduction pure-tone average. RESULTS: One hundred twenty eight children met inclusion criteria. Of these, 54 (42%) had a temporal bone anomaly, and 22 (17%) had ipsilateral BCNC stenosis. At 12 months, rates of progression in the ipsilateral ear were as follows: 12% among those without a temporal bone anomaly, 13% among those with a temporal bone anomaly, and 17% among those with BCNC stenosis. Children with BCNC stenosis had a significantly greater risk of progression in their ipsilateral ear compared with children with no stenosis: hazard ratio (HR) 2.17, 95% confidence interval (CI) (1.01, 4.66), p value 0.046. When we compared children with BCNC stenosis to those with normal temporal bone imaging, we found that the children with stenosis had nearly two times greater risk estimate for progression, but this difference did not reach significance, HR 1.9, CI (0.8, 4.3), p = 0.1. No children with BCNC stenosis developed hearing loss in their contralateral year by 12 months of follow-up. CONCLUSION: Children with bony cochlear nerve canal stenosis may be at increased risk for progression in their ipsilateral ear. Audiometric and medical follow-up for these children should be considered.