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ImportanceIn asthma and other diseases, vitamin D insufficiency is associated with adverse outcomes. It is not known if supplementing inhaled corticosteroids with oral vitamin D3 improves outcomes in patients with asthma and vitamin D insufficiency.ObjectiveTo evaluate if vitamin D supplementation would improve the clinical efficacy of inhaled corticosteroids in patients with symptomatic asthma and lower vitamin D levels.Design, setting, and participantsThe VIDA (Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness in Asthma) randomized, double-blind, parallel, placebo-controlled trial studying adult patients with symptomatic asthma and a serum 25-hydroxyvitamin D level of less than 30 ng/mL was conducted across 9 academic US medical centers in the National Heart, Lung, and Blood Institute's AsthmaNet network, with enrollment starting in April 2011 and follow-up complete by January 2014. After a run-in period that included treatment with an inhaled corticosteroid, 408 patients were randomized.InterventionsOral vitamin D3 (100,000 IU once, then 4000 IU/d for 28 weeks; n = 201) or placebo (n = 207) was added to inhaled ciclesonide (320 µg/d). If asthma control was achieved after 12 weeks, ciclesonide was tapered to 160 µg/d for 8 weeks, then to 80 µg/d for 8 weeks if asthma control was maintained.Main outcomes and measuresThe primary outcome was time to first asthma treatment failure (a composite outcome of decline in lung function and increases in use of β-agonists, systemic corticosteroids, and health care).ResultsTreatment with vitamin D3 did not alter the rate of first treatment failure during 28 weeks (28% [95% CI, 21%-34%] with vitamin D3 vs 29% [95% CI, 23%-35%] with placebo; adjusted hazard ratio, 0.9 [95% CI, 0.6-1.3]). Of 14 prespecified secondary outcomes, 9 were analyzed, including asthma exacerbation; of those 9, the only statistically significant outcome was a small difference in the overall dose of ciclesonide required to maintain asthma control (111.3 µg/d [95% CI, 102.2-120.4 µg/d] in the vitamin D3 group vs 126.2 µg/d [95% CI, 117.2-135.3 µg/d] in the placebo group; difference of 14.9 µg/d [95% CI, 2.1-27.7 µg/d]).Conclusions and relevanceVitamin D3 did not reduce the rate of first treatment failure or exacerbation in adults with persistent asthma and vitamin D insufficiency. These findings do not support a strategy of therapeutic vitamin D3 supplementation in patients with symptomatic asthma.Trial registrationclinicaltrials.gov Identifier: NCT01248065.

BackgroundChronic obstructive lung disease frequently leads to disability. Older patients may experience transitions between states of disability and independence over time.ObjectiveTo identify factors associated with transition between states of disability and independent function in obstructive lung disease.MethodsWe analyzed data on 4,394 participants in the Cardiovascular Health Study who completed prebronchodilator spirometry. We calculated the 1-year probability of developing and resolving impairment in ≥1 instrumental activity of daily living (IADL) or ≥1 activity of daily living (ADL) using transition probability analysis. We identified factors associated with resolving disability using relative risk (RR) regression.ResultsThe prevalence of IADL impairment was higher with moderate (23.9%) and severe (36.9%) airflow obstruction compared to normal spirometry (22.5%; p < 0.001). Among participants with severe airflow obstruction, 23.5% recovered independence in IADLs and 40.5% recovered independence in ADLs. In the adjusted analyses, airflow obstruction predicted the development of IADL, but not ADL impairment. Participants with severe airflow obstruction were less likely to resolve IADL impairment [RR 0.67 and 95% confidence interval (CI) 0.49-0.94]. Compared to the most active individuals (i.e. who walked ≥28 blocks per week), walking less was associated with a decreased likelihood of resolving IADL impairment (7-27 blocks: RR 0.81 and 95% CI 0.69-0.86 and

RationaleRelationships between chronic health conditions and acute infections remain poorly understood. Preclinical studies suggest crosstalk between nervous and immune systems.ObjectivesTo determine bidirectional relationships between cognition and pneumonia.MethodsWe conducted longitudinal analyses of a population-based cohort over 10 years. We determined whether changes in cognition increase risk of pneumonia hospitalization by trajectory analyses and joint modeling. We then determined whether pneumonia hospitalization increased risk of subsequent dementia using a Cox model with pneumonia as a time-varying covariate.Measurements and main resultsOf the 5,888 participants, 639 (10.9%) were hospitalized with pneumonia at least once. Most participants had normal cognition before pneumonia. Three cognition trajectories were identified: no, minimal, and severe rapid decline. A greater proportion of participants hospitalized with pneumonia were on trajectories of minimal or severe decline before occurrence of pneumonia compared with those never hospitalized with pneumonia (proportion with no, minimal, and severe decline were 67.1%, 22.8%, and 10.0% vs. 76.0%, 19.3%, and 4.6% for participants with and without pneumonia, respectively; P < 0.001). Small subclinical changes in cognition increased risk of pneumonia, even in those with normal cognition and physical function before pneumonia (β = -0.02; P < 0.001). Participants with pneumonia were subsequently at an increased risk of dementia (hazard ratio, 2.24 [95% confidence interval, 1.62-3.11]; P = 0.01). Associations were independent of demographics, health behaviors, other chronic conditions, and physical function. Bidirectional relationship did not vary based on severity of disease, and similar associations were noted for those with severe sepsis and other infections.ConclusionsA bidirectional relationship exists between pneumonia and cognition and may explain how a single episode of infection in well-appearing older individuals accelerates decline in chronic health conditions and loss of functional independence.

Little evidence on the validity of simple and widely applicable tools to predict mortality in patients with chronic obstructive pulmonary disease (COPD) exists. To conduct a large international study to validate the ADO index that uses age, dyspnoea and FEV(1) to predict 3-year mortality and to update it in order to make prediction of mortality in COPD patients as generalisable as possible. Individual subject data analysis of 10 European and American cohorts (n=13 914). Population-based, primary, secondary and tertiary care. COPD GOLD stages I-IV. We validated the original ADO index. We then obtained an updated ADO index in half of our cohorts to improve its predictive accuracy, which in turn was validated comprehensively in the remaining cohorts using discrimination, calibration and decision curve analysis and a number of sensitivity analyses. 1350 (9.7%) of all subjects with COPD (60% male, mean age 61 years, mean FEV(1) 66% predicted) had died at 3 years. The original ADO index showed high discrimination but poor calibration (p

Asthma is the most common chronic disease in children, disproportionately affects families with lower incomes, and is a leading reason for acute care visits and hospitalizations. This retrospective cohort study used the Massachusetts All Payer Claims Database (2014–2018) to examine differences in acute care utilization and quality of care for asthma between Medicaid- and privately insured children in Massachusetts. Outcomes included acute care use (emergency department [ED] or hospitalization), ED visits with asthma, routine asthma visits, and filled prescriptions for asthma medications. Multivariable logistic regression was used to account for differences in demographics, ZIP codes, health status, and asthma severity. Overall, 10.0% of Medicaid-insured children and 5.6% of privately insured were classified as having asthma. Among 317,596 child-year observations for children with asthma, 64.4% were insured by Medicaid. Medicaid-insured children had higher rates of any acute care use (50.4% vs. 30.0%) and ED visits with an asthma diagnosis (27.2% vs. 13.3%) compared to privately insured children. Only 65.4% of Medicaid enrollees had at least one routine asthma visit compared to 74.3% of privately insured children. Most children received at least one asthma medication (88.6% Medicaid vs. 83.3% privately insured), but a higher percentage of Medicaid-insured children received at least one rescue medication (84.0% vs. 73.7%), and a lower percentage of Medicaid-insured (46.1% vs. 49.2%) received a controller medication. These results suggest that opportunities for improvement in childhood asthma persist, particularly for children insured by Medicaid. [ABSTRACT FROM AUTHOR]

To examine the association between neighborhood-level social vulnerability and adherence to scheduled ophthalmology appointments. In this retrospective cohort study, records of all patients ≥18 years scheduled for an ophthalmology appointment between September 12, 2020, and February 8, 2021, were reviewed. Primary exposure is neighborhood-level Social Vulnerability Index (SVI) based on the patient's residential location. SVI is a rank score of 15 social factors into four themes (socioeconomic status, household composition/disability, minority status/language, and housing type/transportation), ranging from 0 to 1.0, with higher ranks indicating greater social vulnerability. The overall SVI score and each theme were analyzed separately as the primary exposure of interest in multivariable logistic regression models that controlled for age, sex, appointment status (new or established), race, and distance from clinic. The primary outcome, non-adherence, was defined as missing more than 25% of scheduled appointments. Of 8,322 patients (41% non-Hispanic Black, 24% Hispanic, 22% non-Hispanic White) with scheduled appointments, 28% were non-adherent. Non-adherence was associated with greater social vulnerability (adjusted odds ratio [aOR] per 0.01 increase in overall SVI = 2.46 [95% confidence interval, 1.99, 3.06]) and each SVI theme (socioeconomic status: aOR = 2.38 [1.94, 2.91]; household composition/disability: aOR = = 1.51 [1.26, 1.81]; minority status/language: aOR = 2.03 [1.55, 2.68]; housing type/transportation: aOR = 1.41 [1.16, 1.73]). Neighborhood-level social vulnerability is associated with greater risk of non-adherence to scheduled ophthalmology appointments, controlling for individual characteristics. Multi-level intervention strategies that incorporate neighborhood-level vulnerabilities are needed to reduce disparities in access to ophthalmology care. [ABSTRACT FROM AUTHOR]

Rationale: Interventions to promote adherence to long-term oxygen therapy (LTOT) in chronic obstructive pulmonary disease (COPD) are needed. Objectives: To examine the real-world effectiveness of phone-based peer coaching on LTOT adherence and other outcomes in a pragmatic trial of patients with COPD. Methods: In a hybrid effectiveness/implementation pragmatic trial, patients were randomized to receive phone-based proactive coaching (educational materials, five phone-based peer coaching sessions over 60 d), reactive coaching (educational materials, peer coaching when requested), or usual care. Study staff members collected baseline and outcome data via phone at 30, 60, and 90 days after randomization. Adherence to LTOT over 60 days, the primary effectiveness outcome, was defined as mean LTOT use ≥17.7h/d. LTOT use was calculated using information about home oxygen equipment use in worksheets completed by study participants. Comparisons of adherence to LTOT between each coaching group and the usual care group using multivariable logistic regression models were prespecified as the primary analyses. Secondary effectiveness outcomes included Patient Reported Outcome Management Information System measures for physical, emotional, and social health. We assessed early implementation domains in the reach, adoption, and implementation framework. Results: In 444 participants, the proportions who were adherent to LTOT at 60 days were 74% in usual care, 84% in reactive coaching, and 70% in proactive coaching groups. Although reach, adoption by stakeholder partners, and intervention fidelity were acceptable, complete LTOT adherence data were available in only 73% of participants. Reactive coaching (adjusted odds ratio, 1.77; 97.5% confidence interval, 0.80-3.90) and proactive coaching (adjusted odds ratio, 0.70; 97.5% confidence interval, 0.34-1.46) did not improve adherence to LTOT compared with usual care. However, proactive coaching significantly reduced depressive symptoms and sleep disturbance compared with usual care and reduced depressive symptoms compared with reactive coaching. Unexpectedly, LTOT adherence was significantly lower in the proactive compared with the reactive coaching group. Conclusions: The results were inconclusive about whether a phone-based peer coaching strategy changed LTOT adherence compared with usual care. Further studies are needed to confirm the potential benefits of proactive peer coaching on secondary effectiveness outcomes and differences in LTOT adherence between proactive and reactive peer coaching. Clinical trial registered with ClinicalTrials.gov (NCT02098369). [ABSTRACT FROM AUTHOR]

Background: Pediatric asthma has been identified by regulators, clinicians, clinical trial sponsors, and caregivers as an area in need of novel fit-for-purpose clinical outcome assessments (COAs) developed in accordance with the U.S. Food and Drug Administration's (FDA's) regulatory guidance for evaluating clinical benefit in treatment trials. To address this gap, the Patient-Reported Outcome (PRO) Consortium's Pediatric Asthma Working Group has continued development of 2 COAs to assess asthma signs and symptoms in pediatric asthma clinical trials to support efficacy endpoints: a PRO measure, the Pediatric Asthma Diary—Child (PAD-C) for children 8–11 years old (y.o.) and an observer-reported outcome measure, the Pediatric Asthma Diary-Observer (PAD—O) for caregivers of children 4–11 y.o. This qualitative research aimed to generate evidence regarding the content validity of the PAD-C and PAD-O. Methods: Semi-structured combined concept elicitation and cognitive interviews were conducted with a diverse sample of U.S. participants (15 children 8–11 y.o. and 30 caregivers of children 4–11 y.o.). All children had clinician-diagnosed mild to severe asthma. Interviews explored the experience of pediatric asthma and assessed the understanding and relevance of both measures. Interviews were conducted across 3 iterative rounds to allow for modifications. Results: Concept elicitation findings demonstrated that the core sign/symptom and impact concepts assessed in the PAD-C (cough, hard to breathe, out of breath, wheezing, chest tightness, and nighttime awakenings/symptoms) and PAD-O (cough, difficulty breathing, short of breath, wheezing, and nighttime awakenings/signs) correspond to those most frequently reported by participants; concept saturation was achieved. All PAD-C and PAD-O instructions and core items were well understood and considered relevant by most participants. Feedback from participants, the Pediatric Asthma Working Group, advisory panel, and FDA supported modifications to the measures, including addition of 1 new item to both measures and removal of 1 caregiver item. Conclusions: Findings provide strong support for the content validity of both measures. The cross-sectional measurement properties of both measures and their user experience and feasibility in electronic format will be assessed in a future quantitative pilot study with qualitative exit interviews, intended to support the reliability, construct validity, final content, and, ultimately, FDA qualification of the measures. Plain English summary: Pediatric asthma is one of the most common chronic diseases in children. However, there are problems of underdiagnosis, poor disease management, and undertreatment for many pediatric asthma patients, pressuring healthcare systems worldwide. Evaluating asthma symptoms is an important part of the development of treatments for pediatric asthma. However, there are few clinical outcome assessments (COAs) developed in line with regulatory guidance to directly assess symptom severity and evaluate the benefit of new treatments in children with asthma. In this study, we continued the development of the Pediatric Asthma Diary—Child (PAD-C) and the Pediatric Asthma Diary—Observer (PAD-O), according to regulatory guidance, to assess asthma signs and symptoms in children 4 through 11 years old and address this unmet need. The study aimed to explore the experience of pediatric asthma and assess how well-understood and relevant the measures are. Three rounds of qualitative interviews were conducted with 15 children 8 through 11 years old and 30 caregivers of children 4 through 11 years old with asthma. Results show that both measures are well-understood and assess the relevant and important aspects of pediatric asthma reported by children and caregivers. Findings provide evidence supporting the PAD-C and PAD-O as measures of symptom severity and their future use in pediatric asthma treatment trials. Further research is underway to evaluate their measurement properties and assess the user experience and feasibility of electronic completion, to ultimately support the PAD-C and PAD-O in an ongoing COA qualification process by the United States Food and Drug Administration. [ABSTRACT FROM AUTHOR]