Impact of mail-based continuous positive airway pressure initiation on treatment usage and effectiveness.

PURPOSE: In-person visits with a trained therapist have been standard care for patients initiating continuous positive airway pressure (CPAP). These visits provide an opportunity for hands-on training and an in-person assessment of mask fit. However, to improve access, many health systems are shifting to remote CPAP initiation with equipment mailed to patients. While there are potential benefits of a mailed approach, relative patient outcomes are unclear. Specifically, many have concerns that a lack of in-person training may contribute to reduced CPAP adherence. To inform this knowledge gap, we aimed to compare treatment usage after in-person or mailed CPAP initiation. METHODS: Our medical center shifted from in-person to mailed CPAP dispensation in March 2020 during the COVID-19 pandemic. We assembled a cohort of patients with newly diagnosed obstructive sleep apnea (OSA) who initiated CPAP in the months before (n = 433) and after (n = 186) this shift. We compared 90-day adherence between groups. RESULTS: Mean nightly PAP usage was modest in both groups (in-person 145.2, mailed 140.6 min/night). We did not detect between-group differences in either unadjusted or adjusted analyses (adjusted difference - 0.2 min/night, 95% - 27.0 to + 26.5). CONCLUSIONS: Mail-based systems of CPAP initiation may be able to improve access without reducing CPAP usage. Future work should consider the impact of mailed CPAP on patient-reported outcomes and the impact of different remote setup strategies.

Effect of a Remotely Delivered Self-directed Behavioral Intervention on Body Weight and Physical Health Status Among Adults With Obesity: The D-ELITE Randomized Clinical Trial.

Importance: The effectiveness of remotely delivered, self-directed, weight loss programs in routine clinical practice is largely unknown. Objective: To test whether a self-directed, remotely administered behavioral lifestyle intervention improves weight and self-reported general health status compared with usual care. Design, Setting, and Participants: In this randomized clinical trial, 511 adults with a body mass index (BMI) of 30 or more and less than 45 (based on electronic health record [EHR] weight and height), were enrolled from 30 Veterans Health Administration (VHA) sites between February 15, 2018, and December 18, 2018 (final follow-up February 18, 2021). Interventions: Participants were randomly assigned to the intervention group (n = 254) or the control group (n = 257). Both received usual care. Participants randomized to the intervention received Diabetes Prevention Program-based self-directed videos, handouts, and coaching messages via an online platform or US mail for 12 months. Main Outcomes and Measures: Coprimary outcomes were weight measured in primary care and recorded in the EHR and self-reported general health status using the Medical Outcomes Study 12-Item Short Form Health Survey (SF-12) physical component score (PCS; higher scores are better [range, 0-100]) at the 12-month follow-up. The between-group minimal clinically important differences are 3 kg for weight and 5 points for the SF-12 PCS. Linear mixed models used weights and SF-12 PCS measured at either time point, with participants analyzed according to randomization assignment. Statistical significance for each coprimary outcome was based on a 2-sided α level of .025. Results: Among 511 participants randomized (mean age, 57.4 [SD, 13.9] years; 231 female [45%]), 429 (84.0%) had EHR-based weights and 410 (80.2%) had SF-12 PCS data at 12 months. The unadjusted mean weight at 12 months declined from 102.7 kg to 99.8 kg in the intervention group compared with 101.9 kg to 101.0 kg in the control group (adjusted between-group mean difference, -1.93 [97.5% CI, -3.24 to -0.61]; P = .001). At 12 months, the unadjusted mean SF-12 PCS scores declined from 44.8 to 44.3 among intervention participants compared with 44.5 to 43.2 among control participants (adjusted between-group mean difference, intervention minus control, 0.69 [97.5% CI, -1.11 to 2.49]; P = .39). Cardiovascular events represented the highest percentage of serious adverse events, accounting for 25% of events in the intervention group and 35% in the control group. Conclusions and Relevance: Among adults with obesity, a remotely delivered self-directed, behavioral lifestyle intervention, compared with usual care, resulted in statistically significantly greater weight loss at 12 months, although the difference was not clinically important. There was no significant difference in self-reported general physical health status at 12 months. Trial Registration: ClinicalTrials.gov Identifier: NCT03260140.

Primary Care and Mental Health Prescribers, Key Clinical Leaders, and Clinical Pharmacist Specialists' Perspectives on Opioids and Benzodiazepines.

OBJECTIVE: Due to increased risks of overdose fatalities and injuries associated with coprescription of opioids and benzodiazepines, healthcare systems have prioritized deprescribing this combination. Although prior work has examined providers' perspectives on deprescribing each medication separately, perspectives on deprescribing patients with combined use is unclear. We examined providers' perspectives on coprescribed opioids and benzodiazepines and identified barriers and facilitators to deprescribing. DESIGN: Qualitative study using semistructured interviews. SETTING: One multisite Veterans Affairs (VA) healthcare system in the United States of America. SUBJECTS: Primary care and mental health prescribers, key clinical leaders, clinical pharmacist specialists (N = 39). METHODS: Interviews were audio-recorded, transcribed, and analyzed using thematic analysis. Themes were identified iteratively, through a multidisciplinary team-based process. RESULTS: Analyses identified four themes related to barriers and facilitators to deprescribing: inertia, prescriber self-efficacy, feasibility of deprescribing/tapering, and promoting deprescribing, as well as a fifth theme, consequences of deprescribing. Results highlighted the complexity of deprescribing when multiple prescribers are involved, a need for additional support and time, and concerns about patients' reluctance to discontinue these medications. Facilitators included agreement with the goal of deprescribing and fear of negative consequences if medications are continued. Providers spoke to how deprescribing efforts impaired patient-provider relationships and informed their decisions not to start patients on these medications. CONCLUSIONS: Although providers agree with the goal, prescribers' belief in a limited deprescribing role, challenges with coordination among prescribers, concerns about insufficient time and patients' resistance to discontinuing these medications need to be addressed for efforts to be successful.

Overuse and Misuse of Inhaled Corticosteroids Among Veterans with COPD: a Cross-sectional Study Evaluating Targets for De-implementation.

BACKGROUND: Inhaled corticosteroid (ICS) use among patients with COPD increases the risk of pneumonia and other complications. Current recommendations limit ICS use to patients with frequent or severe COPD exacerbations. However, use of ICS among patients with COPD is common and may be occurring both among those with mild disease (overuse) and those misdiagnosed with COPD (misuse). OBJECTIVE: To identify patients without identifiable indication for ICS and assess patient and provider characteristics associated with potentially inappropriate to targeted in de-implementation efforts DESIGN: We performed a cross-sectional study of patients with COPD in the Veterans Affairs (VA) system with recent spirometry. PARTICIPANTS: After setting an index date, we identified individuals with a clinical diagnosis of COPD who had spirometry completed in the prior 5 years. We excluded individuals with an appropriate indication for ICS based on the 2017 GOLD statement, including asthma and a recent history of frequent or severe exacerbations. MAIN MEASURES: ICS use without identifiable indication KEY RESULTS: We identified 26,536 patients with COPD without an identifiable indication for ICS. Nearly » of patients (n = 6330) filled ≥2 prescriptions for ICS in the year prior to the index date. We found that older age (adjusted prevalence ratio [APR] 1.06 per decade, 95% confidence interval [CI] 1.04-1.08), white race (APR 1.11, 95% CI 1.05-1.19), and more primary care visits (APR 1.05 per visit, 95% CI 1.03-1.07) were associated with increased likelihood of potentially inappropriate use. Primary care clinic complexity and provider training were not associated with ICS use. Among patients misdiagnosed with COPD, we found that 14% used ICS. CONCLUSIONS: Potentially inappropriate ICS use is common among patients with and without airflow obstruction who are diagnosed with COPD. We identified patient comorbidities and patterns of healthcare utilization that increase the likelihood of ICS use that could be targeted for system-level de-implementation interventions.

Practical implementation of noninvasive ventilation in Amyotrophic Lateral Sclerosis: lessons learned from a clinical case series.

PURPOSE: Noninvasive ventilation (NIV) may improve survival and quality of life in Amyotrophic Lateral Sclerosis (ALS) patients. There is a surprising paucity of practical guidelines for office-based implementation and management of NIV outside of tertiary ALS centers. We saw the need for a clinical protocol to allow feasible and consistent NIV management in this patient population. METHODS: We created a clinical protocol for office-based initiation of NIV implemented on consecutive ALS patients referred from our regional ALS multidisciplinary clinic. The protocol provided initial empiric settings using a bilevel device in volume-assured pressure support mode. A respiratory therapist (RT) initiated NIV in an office setting and made adjustments according to patient tolerance and therapy targets outlined in the protocol. Later setting changes were performed at patient or provider request. We evaluated patient adherence and efficacy via device download at 30 days and 1 year. RESULTS: We present data from a case series of the first 14 consecutive patients initiated on NIV over a 20-month period. Our protocol underwent iterative modification based on clinical experience and patient feedback. Early challenges included the significant time and resource burden required to coordinate device downloads and patient follow-up. Early 30-day NIV adherence was variable (median 20 out of 30 days), while 1-year NIV adherence was excellent (median 27.5 out of 30 days). CONCLUSIONS: Our RT-driven clinical NIV protocol was feasible but labor intensive. Achieving real-world adherence of NIV in our ALS patients required iterative protocol adjustment, significant RT provider time, and tele-based follow-up.

Atypical presentations associated with non-polyalanine repeat PHOX2B mutations.

Congenital central hypoventilation syndrome (CCHS) is a disorder of ventilatory control and autonomic dysregulation that can be caused by mutations in the paired-like homeobox 2B (PHOX2B) gene. The majority of CCHS cases are caused by polyalanine repeat mutations (PARMs) in PHOX2B; however, in rare cases, non-polyalanine repeat mutations (NPARMs) have been identified. Here, we report two patients with NPARMs in PHOX2B. Patient 1 has a mild CCHS phenotype seen only on polysomnogram, which was performed for desaturations and stridor following a bronchiolitis episode, and characterized by night-time hypoventilation and a history of ganglioneuroblastoma. She carried a novel de novo missense variant, p.R102S (c.304C > A), in exon 2. Patient 2 has an atypical CCHS phenotype including micrognathia, gastroesophageal reflux, stridor, hypopnea, and intermittent desaturations. Sleep study demonstrated that Patient 2 had daytime and night-time hypercarbia with obstructive sleep apnea, requiring tracheostomy. On PHOX2B sequencing, she carried a recently identified nonsense variant, p.Y78* (c.234C > G), in exon 1. In summary, we present two patients with CCHS and identified NPARMs in PHOX2B who have distinct differences in phenotype severity, further elucidating the range of clinical outcomes in CCHS and illustrating the necessity of considering PHOX2B mutations when encountering atypical CCHS presentations.

Quality of Care Delivered to Veterans with COPD Exacerbation and the Association with 30-Day Readmission and Death.

Quality of chronic obstructive pulmonary disease (COPD) care is thought to be an important intermediate process to improve the well-being of patients admitted to hospital for exacerbation. We sought to examine the quality of inpatient COPD care and the associations with readmission and mortality. We performed a cohort study of 2,364 veterans aged over 40 and hospitalized for COPD between 2005 and 2011 at five Department of Veterans Affairs hospitals. We examined whether patients received six guideline recommended care items including short-acting bronchodilators, corticosteroids, antibiotics, positive-pressure ventilation (in cases of acute hypercarbic respiratory failure), chest imaging, and arterial blood gas measurement. Our primary outcome was all-cause hospital readmission or death within 30 days. Overall quality of care was not significantly associated with readmission or death (acute care aOR 0.98; 95% CI 0.87-1.11; ICU aOR 0.89; 95% CI 0.71-1.13). Delivery of corticosteroids and antibiotics was associated with reduced odds of readmission and death (aOR 0.77; 95% CI 0.61-0.92). Few patients received all of the recommended care items (18% of acute care, 38% of ICU patients). Quality of care did not vary by race or sex but did vary significantly across sites and did not improve over time. Our composite measure of COPD care quality was not associated with readmission or death. Further efforts are needed to improve care delivery to patients hospitalized with COPD.

Low likelihood of intracranial hemorrhage in patients with cirrhosis and altered mental status.

BACKGROUND & AIMS: Given the myriad causes of altered mental status (AMS), patients with cirrhosis and hepatic encephalopathy often present a diagnostic dilemma. In light of the perceived bleeding tendency of patients with cirrhosis, intracranial hemorrhage (ICH) is often feared, so these patients frequently undergo non-contrast computed tomography (CT) of the head. However, little is known about the diagnostic yield of CT for patients with cirrhosis presenting with AMS. METHODS: We analyzed all unique admissions of patients with cirrhosis who underwent head CT from 2003 through 2013 (N = 462) at the Beth Israel Deaconess Medical Center in Boston. By using blinded reviewers, we coded the indications and results of the CT scans separately and evaluated patient characteristics associated with acute findings. RESULTS: A higher proportion of patients who presented with falls or trauma, focal neurologic signs, or history of ICH were found to have ICH (13 of 146, 8.9%) than of patients who presented with AMS, headache, or fever (1 of 316, 0.3%; P < .0001). The odds ratio of ICH in patients with low-risk indications was 0.02 (95% confidence interval, 0.001-0.14). The number needed to scan (NNS) for each positive result from CT varied by indication: focal neurologic deficits (NNS = 9), fall/trauma (NNS = 20), and AMS (NNS = 293). There was no association between presence of new, acute ICH and platelet count, international normalized ratio, level of creatinine, or Model for End-Stage Liver Disease score. CONCLUSIONS: Despite abnormal hemostatic indices, patients with cirrhosis presenting with AMS in the absence of focal neurologic deficits or trauma have a low likelihood of ICH.

Inhaler Formulary Change in COPD and the Association with Exacerbations, Health Care Utilization, and Costs.

Rationale: Prescription formularies specify which medications are available to patients. Formularies change frequently, potentially forcing patients to switch medications for nonclinical indications (nonmedical switching). Nonmedical switching is known to impact disease control and adherence. The consequences of nonmedical switching have not been rigorously studied in COPD. Methods: We conducted a cohort study of Veterans with COPD on inhaler therapy in January 2016 when formoterol was removed from the Department of Veterans Affairs (VA) national formulary. A 2-point difference-in-differences analysis using multivariable negative binomial and generalized linear models was performed to estimate the association of the formulary change with patient outcomes in the 6 months before and after the change. Our primary outcome was the number of COPD exacerbations in 6 months, with secondary outcomes of total health care encounters and encounter-related costs in 6 months. Results: We identified 10,606 Veterans who met our inclusion criteria, of which 409 (3.9%) experienced nonmedical switching off formoterol. We did not identify a change in COPD exacerbations (-0.04 exacerbations; 95% confidence interval [CI] -0.12, 0.03) associated with the formulary change. In secondary outcome analysis, we did not observe a change in the number of health care encounters (-0.12 visits; 95% CI -1.00, 0.77) or encounter-related costs ($369; 95% CI -$1141, $1878). Conclusions: Among COPD patients on single inhaler therapy, nonmedical inhaler switches due to formulary discontinuation of formoterol were not associated with changes in COPD exacerbations, encounters, or encounter-related costs. Additional research is needed to confirm our findings in more severe disease and other settings.

Assessment of Obstructive Sleep Apnea Among Patients With Chronic Obstructive Pulmonary Disease in Primary Care.

Study Objectives: Observational studies link untreated obstructive sleep apnea (OSA) with adverse outcomes in chronic obstructive pulmonary disease (COPD). The first step in addressing OSA is a clinical assessment. However, given competing demands and a lack of high-quality evidence, it is unclear how often such assessments occur. We explored the documentation of OSA assessment among patients with COPD in primary care, and the patient and provider characteristics associated with these assessments. Methods: We conducted a cross-sectional study of patients with clinically diagnosed COPD at 2 primary care practices. We abstracted charts to determine whether providers assessed OSA, defined as documentation of symptoms, treatment, or a referral to sleep medicine. We performed multivariable mixed-effects logistic regression to assess the associations of patient and provider characteristics with OSA assessment. Results: Among 641 patients with clinically diagnosed COPD, 146 (23%) had OSA assessed over a 1-year period. Positive associations with OSA assessment included body mass index ≥ 30 (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.8-7.0), pulmonary subspecialist visits (OR 3.9, 95%CI 2.4-6.3), and a prior sleep study demonstrating OSA documented within the electronic medical record (OR 18.0, 95%CI 9.0-35.8). Notably, patients identifying as Black were less likely to have OSA assessed than those identifying as White (OR 0.5, 95%CI 0.2-0.9). Conclusions: Providers document an assessment of OSA among a quarter of patients with COPD. Our findings highlight the importance of future work to rigorously test the impact of assessment on important health outcomes. Our findings also reinforce that additional strategies are needed to improve the equitable delivery of care.

Risks of Zolpidem among Patients with Chronic Obstructive Pulmonary Disease.

Rationale: Nonbenzodiazepine benzodiazepine receptor agonists (NBZRA, e.g., zolpidem) are frequently used to treat insomnia among patients with chronic obstructive pulmonary disease (COPD). However, multiple observational studies find that patients with COPD who are prescribed NBZRAs have greater risks for mortality and respiratory complications than patients without such prescriptions. Without an active comparator, these studies are susceptible to confounding by indication. Objectives: Compare the risk of death or inpatient COPD exacerbation among patients receiving zolpidem relative to patients receiving other hypnotics. Methods: Using nationwide Veterans Health Administration (VA) data, we identified patients with clinically diagnosed COPD and new receipt of zolpidem or another hypnotic available on VA formulary without prior authorization (melatonin, trazodone, doxepin). We excluded those receiving traditional benzodiazepines or multiple concurrent hypnotics. We propensity-matched patients receiving zolpidem to other hypnotics on 32 variables, including demographics, comorbidities, and markers of COPD severity. We compared risk of the primary composite outcome of death or inpatient COPD exacerbation over 1 year. In secondary analyses, we propensity-matched patients receiving zolpidem to those without hypnotic receipt. Results: Among 283,740 patients meeting inclusion criteria, 1,126 (0.4%) received zolpidem and 3,057 (1.1%) received other hypnotics. We propensity-matched patients receiving zolpidem 1:1 to peers receiving other hypnotics. We did not find a difference in the primary composite outcome of death or inpatient exacerbation (hazard ratio, 0.97; 95% confidence interval [CI], 0.77-1.23). In secondary analyses comparing patients receiving zolpidem to matched peers without hypnotic receipt, we observed greater risk of death or inpatient exacerbation with zolpidem (hazard ratio, 1.40; 95% CI, 1.09-1.81). Conclusions: Among patients with COPD, we did not observe greater risks after new receipt of zolpidem relative to other hypnotics. However, we did observe greater risks relative to those without hypnotic receipt. This latter finding may reflect: 1) residual, unmeasured confounding related to insomnia; or 2) true adverse effects of hypnotics across classes. Future work is needed to better understand the risks of hypnotics in COPD.

The Impact of Changing Race-Specific Equations for Lung Function Tests among Veterans with COPD.

RATIONALE: The American Thoracic Society recommended a single reference equation for spirometry but the impact to patients is not known. OBJECTIVE: To estimate the effect of changing to a single reference equation among Veterans with chronic obstructive pulmonary disease (COPD). METHODS: Cross-sectional study including Veterans aged ≥40 to ≤89 years with COPD and spirometry results from 21 facilities between 2010 - 2019. We collected race/ethnicity data from the electronic health record. We estimated the percentage change in the number of Veterans with lung function meeting clinical thresholds used to determine eligibility for lung resection for cancer, lung volume reduction surgery (LVRS), and lung transplant referral. We estimated the change for each level of VA service connection and financial impact. RESULTS: We identified 44,892 Veterans; Asian (0.5%), Black (11.8%), White (80.8%), and Hispanic (1.8%). When changing to a single reference equation, Asian and Black Veterans had reduced predicted lung function that could result in less surgical lung resection (4.4% and 11.1% respectively), while increasing LVRS (1.7% and 3.8%), and lung transplant evaluation for Black Veterans (1.2%). White Veterans had increased predicted lung function and could experience increased lung resection (8.1%), with less LVRS (3.3%), and lung transplant evaluation (0.9%). Some Asian and Black Veterans could experience an increase in monthly disability payments (+$540.38 and $398.38), while Hispanic White and White Veterans could see a decrease (-$588.79). When aggregated, Hispanic Veterans experienced changes attributable to their racial identity, and because this sample was predominantly Hispanic White, had similar results to White Veterans. CONCLUSIONS: Changing the reference equation could affect access to treatment and disability benefits, depending on race. If adopted, the use of discrete clinical thresholds needs to be reassessed, considering patient-centered outcomes.

Trends and Rural-Urban Differences in the Initial Prescription of Low-Value Inhaled Corticosteroids among U.S. Veterans with Chronic Obstructive Pulmonary Disease.

Rationale: Guidelines recommend inhaled corticosteroids (ICS) for patients with chronic obstructive pulmonary disease (COPD) and select indications, including asthma history, high exacerbation risk, or high serum eosinophils. ICS are commonly prescribed outside of these indications, despite evidence of harm. We defined a "low-value" ICS prescription as the receipt of an ICS without evidence of a guideline-recommended indication. ICS prescription patterns are not well characterized and could inform health system interventions to reduce low-value practices. Objectives: To evaluate the national trends in initial low-value ICS prescriptions in the U.S. Department of Veterans Affairs and to determine whether rural-urban differences in low-value ICS prescribing exist. Methods: We performed a cross-sectional study between January 4, 2010, and December 31, 2018, identifying veterans with COPD who were new users of inhaler therapy. We defined low-value ICS as prescriptions in patients with 1) no asthma, 2) low risk of future exacerbation (Global Initiative for Chronic Obstructive Lung Disease group A or B), and 3) serum eosinophils <300 cells/µl. We performed multivariable logistic regression to evaluate trends in low-value ICS prescription over time, adjusting for potential confounders. We performed fixed effects logistic regression to assess rural-urban prescribing patterns. Results: We identified a total of 131,009 veterans with COPD starting inhaler therapy, 57,472 (44%) of whom were prescribed low-value ICS as initial therapy. From 2010 to 2018, the probability of receiving low-value ICS as initial therapy increased by 0.42 percentage points per year (95% confidence interval, 0.31-0.53). Compared with urban residence, rural residence was associated with a 2.5-percentage-point (95% confidence interval, 1.9-3.1) higher probability of receiving low-value ICS as initial therapy. Conclusions: The prescription of low-value ICS as initial therapy is common and increasing slightly over time for both rural and urban veterans. Given the widespread and persistent nature of low-value ICS prescribing, health system leaders should consider system-wide approaches to address this low-value prescribing practice.

Sleep Testing and Mortality in a Propensity-matched Cohort of Patients with Chronic Obstructive Pulmonary Disease.

Rationale: Many advocate the application of propensity-matching methods to real-world data to answer key questions around obstructive sleep apnea (OSA) management. One such question is whether identifying undiagnosed OSA impacts mortality in high-risk populations, such as those with chronic obstructive pulmonary disease (COPD). Objectives: Assess the association of sleep testing with mortality among patients with COPD and a high likelihood of undiagnosed OSA. Methods: We identified patients with COPD and a high likelihood of undiagnosed OSA. We then distinguished those receiving sleep testing within 90 days of index COPD encounters. We calculated propensity scores for testing based on 37 variables and compared long-term mortality in matched groups. In sensitivity analyses, we compared mortality using inverse propensity weighting and instrumental variable methods. We also compared the incidence of nonfatal events including adverse outcomes (hospitalizations and COPD exacerbations) and routine services that are regularly indicated in COPD (influenza vaccination and pulmonary function testing). We compared the incidence of each nonfatal event as a composite outcome with death and separately compared the marginal probability of each nonfatal event independently, with death as a competing risk. Results: Among 135,958 patients, 1,957 (1.4%) received sleep testing. We propensity matched all patients with sleep testing to an equal number without testing, achieving excellent balance on observed confounders, with standardized differences < 0.10. We observed lower mortality risk among patients with sleep testing (incidence rate ratio, 0.88; 95% confidence interval [CI], 0.79-0.99) and similar results using inverse propensity weighting and instrumental variable methods. Contrary to mortality, we found that sleep testing was associated with a similar or greater risk for nonfatal adverse events, including inpatient COPD exacerbations (subhazard ratio, 1.29; 95% CI, 1.02-1.62) and routine services like influenza vaccination (subhazard ratio, 1.26; 95% CI, 1.17-1.36). Conclusions: Our disparate findings can be interpreted in multiple ways. Sleep testing may indeed cause both reduced mortality and greater incidence of nonfatal adverse outcomes and routine services. However, it is also possible that our findings stem from residual confounding by patients' likelihood of accessing care. Given the limitations of propensity-based analyses, we cannot confidently distinguish these two possibilities. This uncertainty highlights the limitations of using propensity-based analyses to guide patient care and policy decisions.