Evaluating and identifying changes in the rate of unplanned discharge among Department of Veterans Affairs (VA) facilities providing substance use disorder residential care.

INTRODUCTION: Quality improvement (QI) methods play a critical role in ensuring that patients receive high-quality and timely care. Healthcare systems should use valid and reliable measures to inform QI efforts. Mental health settings including substance use disorder (SUD) residential programs have been slow to develop and incorporate quality measurement into routine practice. Unplanned discharge is of particular concern because this event is associated with harm including suicide. Healthcare systems require criteria that they can use to operationalize unplanned discharge as a quality measure in SUD residential programs. METHODS: The study included all discharges from the Department of Veterans Affairs (VA) residential SUD programs between 2018 and 2022. The study calculated crude and adjusted rates of irregular discharge. The study used the first two years of observation (2018-2019) in a logistic regression model to determine the parameter estimates for three important covariates, age, risk for homelessness, and principal diagnosis. The study tested permutations of bin size (N) and days (D) per bin to identify a single set of parameters to enable small and large facilities to have sufficient power to detect out-of-control processes (i.e., significant worsening or improvement in rates). Aligned with standard nomenclature, the study calculated the control limits based on three standard deviations (SD). Values that fell above or below three SD were statistically significant. RESULTS: The cohort included 56 facilities (26,361 discharges). Irregular discharge was associated with younger age (18-40 years) and a principal diagnosis of a drug use disorder. Testing parameter values of 100 discharges (N) over 120 days (D) would yield enough power to detect modest relative changes to the irregular discharge rate for small and large facilities while testing frequently enough to make the evaluations temporally relevant. Because secular trends such as staff changes over time will impact results, the quality control method should allow for real-time feedback to those most proximal to the event. CONCLUSIONS: The study created a set of parameters and a methodology that residential SUD programs can use to operationalize unplanned discharge locally. These data could assist programs in conducting QI work to address unplanned discharge and related harms.

The role of maximal inspiratory pressure on functional performance in adults with heart failure.

BACKGROUND: Exercise intolerance is common among adults with heart failure (HF) and is a strong prognostic indicator. We examined maximal inspiratory pressure (MIP) as an indicator of maximal and submaximal exercise capacity in older HF patients. METHODS: Fifty-one patients age ≥ 50 years with HF underwent MIP testing via the PrO2 device. Peak oxygen uptake (VO2), 6 min walk distance (6MWD), 30 s sit-to-stand test (STS), gait speed (GS), grip strength and lower extremity muscle strength [one-repetition maximum (1RM)] were measured. Correlation and exploratory multiple regression analyses investigated relationships between MIP, left ventricular ejection fraction (LVEF), age, body mass index (BMI) and physical function. MIP was then stratified by median (64 cm H2O), and endpoints were compared between median groups. RESULTS: The median age was 69 years [interquartile range (IQR): 66-73], and the median LVEF was 36.5% (IQR: 30%-45%). Regression identified MIP as an independent predictor for grip strength, 6MWD, 1RM weight and 30 s STS after adjustment for age, BMI and LVEF. MIP greater than the median (n = 25) independently predicted and reflected greater peak VO2 [14.2 (12.8-18.1) vs. 11.5 (9.7-13.0) mL/kg/min; P = 0.0007] as well as 6MWD, 1RM, 30 s STS and GS (all P < 0.05). CONCLUSION: The analysis demonstrates that MIP is a novel biometric for exercise tolerance in adults with HF. Assessments of MIP are safe and convenient, with the potential to enhance routine HF surveillance and provide novel biometrics to guide HF therapeutics.

Treatment of Sleep Apnea and Reduction in Blood Pressure: The Role of Heart Rate Response and Hypoxic Burden.

BACKGROUND: Obstructive sleep apnea is associated with increased blood pressure (BP). Obstructive sleep apnea treatment reduces BP with substantial variability, not explained by the apnea-hypopnea index, partly due to inadequate characterization of obstructive sleep apnea's physiological consequences, such as oxygen desaturation, cardiac autonomic response, and suboptimal treatment efficacy. We sought to examine whether a high baseline heart rate response (ΔHR), a marker of high cardiovascular risk in obstructive sleep apnea, predicts a larger reduction in post-treatment systolic BP (SBP). Furthermore, we aimed to assess the extent to which a reduction in SBP is explained by a treatment-related reduction in hypoxic burden (HB). METHODS: ΔHR and HB were measured from pretreatment and posttreatment polygraphy, followed by a 24-hour BP assessment in 168 participants treated with continuous positive airway pressure or nocturnal supplemental oxygen from the HeartBEAT study (Heart Biomarker Evaluation in Apnea Treatment). Multiple linear regression models assessed whether high versus mid (reference) ΔHR predicted a larger reduction in SBP (primary outcome) and whether there was an association between treatment-related reductions in SBP and HB. RESULTS: A high versus mid ΔHR predicted improvement in SBP (adjusted estimate, 5.8 [95% CI, 1.0-10.5] mm Hg). Independently, a greater treatment-related reduction in HB was significantly associated with larger reductions in SBP (4.2 [95% CI, 0.9-7.5] mm Hg per 2 SD treatment-related reduction in HB). Participants with substantial versus minimal treatment-related reductions in HB had a 6.5 (95% CI, 2.5-10.4) mm Hg drop in SBP. CONCLUSIONS: A high ΔHR predicted a more favorable BP response to therapy. Furthermore, the magnitude of the reduction in BP was partly explained by a greater reduction in HB.

CPAP may promote an endothelial inflammatory milieu in sleep apnoea after coronary revascularization.

BACKGROUND: Continuous positive airway pressure (CPAP) has failed to reduce cardiovascular risk in obstructive sleep apnoea (OSA) in randomized trials. CPAP increases angiopoietin-2, a lung distension-responsive endothelial proinflammatory marker associated with increased cardiovascular risk. We investigated whether CPAP has unanticipated proinflammatory effects in patients with OSA and cardiovascular disease. METHODS: Patients with OSA (apnoea-hypopnea index [AHI] ≥15 events/h without excessive sleepiness) in the Randomized Intervention with CPAP in Coronary Artery Disease and OSA study were randomized to CPAP or usual care following coronary revascularization. Changes in plasma levels of biomarkers of endothelial (angiopoietin-2, Tie-2, E-selectin, vascular endothelial growth factor [VEGF-A]) and lung epithelial (soluble receptor of advanced glycation end-products [sRAGE]) function from baseline to 12-month follow-up were compared across groups and associations with cardiovascular morbidity and mortality assessed. FINDINGS: Patients with OSA (n = 189; 84% men; age 66 ± 8 years, BMI 28 ± 3.5 kg/m2, AHI 41 ± 23 events/h) and 91 patients without OSA participated. Angiopoietin-2 remained elevated whereas VEGF-A declined significantly over 12 months in the CPAP group (n = 91). In contrast, angiopoietin-2 significantly declined whereas VEGF-A remained elevated in the usual care (n = 98) and OSA-free groups. The changes in angiopoietin-2 and VEGF-A were significantly different between CPAP and usual care, whereas Tie-2, sRAGE and E-selectin were similar. Greater 12-month levels of angiopoietin-2 were associated with greater mortality. Greater CPAP levels were associated with worse cardiovascular outcomes. INTERPRETATION: Greater CPAP levels increase proinflammatory, lung distension-responsive angiopoietin-2 and reduce cardioprotective angiogenic factor VEGF-A compared to usual care, which may counteract the expected cardiovascular benefits of treating OSA. FUNDING: National Institutes of Health/National Heart, Lung, and Blood Institute; Swedish Research Council; Swedish Heart-Lung Foundation; ResMed Foundation.

Genetic Analysis of Obstructive Sleep Apnea and Its Relationship with Severe COVID-19.

Rationale: Although patients with obstructive sleep apnea (OSA) have a higher risk for coronavirus disease (COVID-19) hospitalization, the causal relationship has remained unexplored. Objectives: To understand the causal relationship between OSA and COVID-19 by leveraging data from vaccination and electronic health records, genetic risk factors from genome-wide association studies, and Mendelian randomization. Methods: We elucidated genetic risk factors for OSA using FinnGen (total N = 377,277), performing genome-wide association. We used the associated variants as instruments for univariate and multivariate Mendelian randomization (MR) analyses and computed absolute risk reduction against COVID-19 hospitalization with or without vaccination. Results: We identified nine novel loci for OSA and replicated our findings in the Million Veteran Program. Furthermore, MR analysis showed that OSA was a causal risk factor for severe COVID-19 (P = 9.41 × 10-4). Probabilistic modeling showed that the strongest genetic risk factor for OSA at the FTO locus reflected a signal of higher body mass index (BMI), whereas BMI-independent association was seen with the earlier reported SLC9A4 locus and a MECOM locus, which is a transcriptional regulator with 210-fold enrichment in the Finnish population. Similarly, multivariate MR analysis showed that the causality for severe COVID-19 was driven by BMI (multivariate MR P = 5.97 × 10-6, ß = 0.47). Finally, vaccination reduced the risk for COVID-19 hospitalization more in the patients with OSA than in the non-OSA controls, with respective absolute risk reductions of 13.3% versus 6.3%. Conclusions: Our analysis identified novel genetic risk factors for OSA and showed that OSA is a causal risk factor for severe COVID-19. The effect is predominantly explained by higher BMI and suggests BMI-dependent effects at the level of individual variants and at the level of comorbid causality.

Long-term health outcomes for patients with obstructive sleep apnea: placing the Agency for Healthcare Research and Quality report in context-a multisociety commentary.

This multisociety commentary critically examines the Agency for Healthcare Research and Quality (AHRQ) final report and systematic review on long-term health outcomes in obstructive sleep apnea. The AHRQ report was commissioned by the Centers for Medicare & Medicaid Services and particularly focused on the long-term patient-centered outcomes of continuous positive airway pressure, the variability of sleep-disordered breathing metrics, and the validity of these metrics as surrogate outcomes. This commentary raises concerns regarding the AHRQ report conclusions and their potential implications for policy decisions. A major concern expressed in this commentary is that the AHRQ report inadequately acknowledges the benefits of continuous positive airway pressure for several established, long-term clinically important outcomes including excessive sleepiness, motor vehicle accidents, and blood pressure. While acknowledging the limited evidence for the long-term benefits of continuous positive airway pressure treatment, especially cardiovascular outcomes, as summarized by the AHRQ report, this commentary reviews the limitations of recent randomized controlled trials and nonrandomized controlled studies and the challenges of conducting future randomized controlled trials. A research agenda to address these challenges is proposed including study designs that may include both high quality randomized controlled trials and nonrandomized controlled studies. This commentary concludes by highlighting implications for the safety and quality of life for the millions of people living with obstructive sleep apnea if the AHRQ report alone was used by payers to limit coverage for the treatment of obstructive sleep apnea while not considering the totality of available evidence. CITATION: Patil SP, Billings ME, Bourjeily G, et al. Long-term health outcomes for patients with obstructive sleep apnea: placing the Agency for Healthcare Research and Quality report in context-a multisociety commentary. J Clin Sleep Med. 2024;20(1):135-149.

Loop Gain as a Predictor of Blood Pressure Response in Patients Treated for Obstructive Sleep Apnea: Secondary Analysis of a Clinical Trial.

Rationale: Randomized trials have shown inconsistent cardiovascular benefits from obstructive sleep apnea (OSA) therapy. Intermittent hypoxemia can increase both sympathetic nerve activity and loop gain ("ventilatory instability"), which may thus herald cardiovascular treatment benefit. Objectives: To test the hypothesis that loop gain predicts changes in 24-hour mean blood pressure (MBP) in response to OSA therapy and compare its predictive value against that of other novel biomarkers. Methods: The HeartBEAT (Heart Biomarker Evaluation in Apnea Treatment) trial assessed the effect of 12 weeks of continuous positive airway pressure (CPAP) versus oxygen versus control on 24-hour MBP. We measured loop gain and hypoxic burden from sleep tests and identified subjects with a sleepy phenotype using cluster analysis. Associations between biomarkers and 24-h MBP were assessed in the CPAP/oxygen arms using linear regression models adjusting for various covariates. Secondary outcomes and predictors were analyzed similarly. Results: We included 93 and 94 participants in the CPAP and oxygen arms, respectively. Overall, changes in 24-hour MBP were small, but interindividual variability was substantial (mean [standard deviation], -2 [8] and 1 [8] mm Hg in the CPAP and oxygen arms, respectively). Higher loop gain was significantly associated with greater reductions in 24-hour MBP independent of covariates in the CPAP arm (-1.5 to -1.9 mm Hg per 1-standard-deviation increase in loop gain; P ⩽ 0.03) but not in the oxygen arm. Other biomarkers were not associated with improved cardiovascular outcomes. Conclusions: To our knowledge, this is the first study suggesting that loop gain predicts blood pressure response to CPAP therapy. Eventually, loop gain estimates may facilitate patient selection for research and clinical practice. Clinical trial registered with www.clinicaltrials.gov (NCT01086800).

Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration.

Sleep duration has been linked to a wide range of negative health outcomes and to reduced life expectancy. We present genome-wide association studies of short ( ≤ 5 h) and long ( ≥ 10 h) sleep duration in adults of European (N = 445,966), African (N = 27,785), East Asian (N = 3141), and admixed-American (N = 16,250) ancestry from UK Biobank and the Million Veteran Programme. In a cross-population meta-analysis, we identify 84 independent loci for short sleep and 1 for long sleep. We estimate SNP-based heritability for both sleep traits in each ancestry based on population derived linkage disequilibrium (LD) scores using cov-LDSC. We identify positive genetic correlation between short and long sleep traits (rg = 0.16 ± 0.04; p = 0.0002), as well as similar patterns of genetic correlation with other psychiatric and cardiometabolic phenotypes. Mendelian randomisation reveals a directional causal relationship between short sleep and depression, and a bidirectional causal relationship between long sleep and depression.

An Analysis of Irregular Discharges From Residential Treatment Programs in the Department of Veterans Affairs Health Care System.

INTRODUCTION: Veteran populations are frequently diagnosed with mental health conditions such as substance use disorder and PTSD. These conditions are associated with adverse outcomes including a higher risk of suicide. The Veterans Health Administration (VHA) has designed a robust mental health system to address these concerns. Veterans can access mental health treatment in acute inpatient, residential, and outpatient settings. Residential programs play an important role in meeting the needs of veterans who need more structure and support. Residential specialty types in the VHA include general mental health, substance use disorder, PTSD, and homeless/work programs. These programs are affiliated with a DVA facility (i.e., medical center). Although residential care can improve outcomes, there is evidence that some patients are discharged from these settings before achieving the program endpoint. These unplanned discharges are referred to using language such as against medical advice, self-discharge, or irregular discharge. Concerningly, unplanned discharges are associated with patient harm including death by suicide. Although there is some initial evidence to locate factors that predict irregular discharge in VHA residential programs, no work has been done to examine features associated with irregular discharge in each residential specialty. METHODS: We conducted a retrospective cohort study of patients who were discharged from VHA residential treatment programs between January 2018 and September 2022. We included the following covariates: Principal diagnosis, gender, age, race/ethnicity, number of physical health conditions, number of mental health diagnostic categories, marital status, risk of homelessness, urbanicity, and service connection. We considered two discharge types: Regular and irregular. We used logistic regression to determine the odds of irregular discharge using models stratified by bed specialty as well as combined odds ratios and 95% CIs across program specialties. The primary purposes are to identify factors that predict irregular discharge and to determine if the factors are consistent across bed specialties. In a secondary analysis, we calculated facility-level adjusted rates of irregular discharge, limiting to facilities with at least 50 discharges. We identified the amount of residual variation that exists between facilities after adjusting for patient factors. RESULTS: A total of 279 residential programs (78,588 patients representing 124,632 discharges) were included in the analysis. Substance use disorder and homeless/work programs were the most common specialty types. Both in the overall and stratified analyses, the number of mental health diagnostic categories and younger age were predictors of irregular discharge. In the facility analysis, there was substantial variation in irregular discharge rates across residential specialties even after adjusting for all patient factors. For example, PTSD programs had a mean adjusted irregular discharge rate of 15.3% (SD: 7.4; range: 2.1-31.2; coefficient of variation: 48.4%). CONCLUSIONS: Irregular discharge is a key concern in VHA residential care. Patient characteristics do not account for all of the observed variation in rates across residential specialty types. There is a need to develop specialty-specific measures of irregular discharge to learn about system-level factors that contribute to irregular discharge. These data can inform strategies to avoid harms associated with irregular discharge.

Relevance of cortical arousals for risk stratification in sleep apnea: a 3 cohort analysis.

STUDY OBJECTIVES: There is uncertainty on best approaches for defining apnea-hypopnea events. To clarify the contributions of desaturation vs arousal to defining hypopneas, we examined the associations of events with desaturation (≥ 3%) but not arousal (apnea-hypopnea index [AHI]≥3%Only) vs events with arousals but no desaturation (AHIArOnly) with obstructive sleep apnea-related comorbidities and incident cardiovascular disease across multiple cohorts. METHODS: In the Sleep Heart Health Study (n = 5,473), the Multi-Ethnic Study of Atherosclerosis (n = 1,904), and the Osteoporotic Fractures in Men Study (n = 2,685), we examined the independent associations of AHI≥3%Only and AHIArOnly with hypertension, diabetes, and daytime sleepiness, and incident cardiovascular disease. RESULTS: After adjusting for covariates and AHI based on events with electroencephalogram arousal (regardless of desaturation), AHI≥3%Only was associated with hypertension in Sleep Heart Health Study (odds ratio: 1.12; 95% confidence interval: 1.04,1.21), per 1 standard deviation increase). Similar associations were observed in the Multi-Ethnic Study of Atherosclerosis and Osteoporotic Fractures in Men Study, as well as for associations with diabetes (odds ratio: 1.30; 1.09,1.54, and 1.25; 1.07,1.47, respectively), sleepiness (odds ratio: 1.19; 1.00,1.41; and 1.17; 1.01-1.35), and incident cardiovascular disease (hazard ratio: 1.37; 1.05,1.77 and 1.14; 1.00,1.29). In contrast, after adjusting for events with desaturation (regardless of arousal), AHIArOnly was unassociated with these outcomes. In Sleep Heart Health Study, greater baseline obstructive sleep apnea severity was associated with a reduction in arousal frequency over 5 years (P < .0001). CONCLUSIONS: In middle-aged and older individuals, addition of events with arousals does not improve the strength of associations with comorbidities or incident cardiovascular disease. Research is needed to understand generalizability to younger individuals and the mechanistic role of arousals in obstructive sleep apnea. CITATION: Azarbarzin A, Sands SA, Han S, et al. Relevance of cortical arousals for risk stratification in sleep apnea: a 3 cohort analysis. J Clin Sleep Med. 2023;19(8):1475-1484.

Genome-wide association study of obstructive sleep apnoea in the Million Veteran Program uncovers genetic heterogeneity by sex.

BACKGROUND: Genome-wide association studies (GWAS) for obstructive sleep apnoea (OSA) are limited due to the underdiagnosis of OSA, leading to misclassification of OSA, which consequently reduces statistical power. We performed a GWAS of OSA in the Million Veteran Program (MVP) of the U.S. Department of Veterans Affairs (VA) healthcare system, where OSA prevalence is close to its true population prevalence. METHODS: We performed GWAS of 568,576 MVP participants, stratified by biological sex and by harmonized race/ethnicity and genetic ancestry (HARE) groups of White, Black, Hispanic, and Asian individuals. We considered both BMI adjusted (BMI-adj) and unadjusted (BMI-unadj) models. We replicated associations in independent datasets, and analysed the heterogeneity of OSA genetic associations across HARE and sex groups. We finally performed a larger meta-analysis GWAS of MVP, FinnGen, and the MGB Biobank, totalling 916,696 individuals. FINDINGS: MVP participants are 91% male. OSA prevalence is 21%. In MVP there were 18 and 6 genome-wide significant loci in BMI-unadj and BMI-adj analyses, respectively, corresponding to 21 association regions. Of these, 17 were not previously reported in association with OSA, and 13 replicated in FinnGen (False Discovery Rate p-value < 0.05). There were widespread significant differences in genetic effects between men and women, but less so across HARE groups. Meta-analysis of MVP, FinnGen, and MGB biobank revealed 17 additional, previously unreported, genome-wide significant regions. INTERPRETATION: Sex differences in genetic associations with OSA are widespread, likely associated with multiple OSA risk factors. OSA shares genetic underpinnings with several sleep phenotypes, suggesting shared aetiology and causal pathways. FUNDING: Described in acknowledgements.

Intense solar activity reduces urinary 6-sulfatoxymelatonin in patients with COPD.

BACKGROUND: Little is known about the link between solar activity and variations in melatonin. In this study, we investigated if melatonin's major urinary metabolite, urinary 6-sulfatoxymelatonin (aMT6s), is lowest under periods of intense solar activity. METHODS: We investigated associations between high-energy solar particle events [Coronal Mass Ejection (CME) mass, speed and energy] on creatinine-adjusted aMT6s (aMT6sr) concentrations in 140 patients with chronic obstructive pulmonary disease (COPD) using up to four seasonal urine samples (n = 440). Mixed effect models with a random intercept for each subject were used to estimate associations, including effect modification attributable to diabetes, obesity, and reduced pulmonary function. RESULTS: Higher values of CME were associated with reduced aMT6sr concentrations, with stronger associations in patients with diabetes. An interquartile range (IQR) increase in natural log CMEspeed averaged through two days before urine collection was associated with a reduction of 9.3% aMT6sr (95%CI: - 17.1%, - 0.8%) in aMT6sr. There was a greater reduction in aMT6sr in patients with diabetes (- 24.5%; 95%CI: - 35.9%, - 11.6%). In patients without diabetes there was no meaningful association (- 2.2%; 95%CI: - 12%, 8.4%). There were similar associations with CMEenergy and CMEmass. There was no effect modification attributable to reduced pulmonary function or obesity. CONCLUSIONS: This is the first study in patients with COPD to demonstrate strong detrimental impact of high-energy solar particle events on aMT6sr, with greater associations in patients with diabetes. Since melatonin is an anti-oxidant, it is possible that adverse effects of intense solar activity may be attributable to a reduction in circulating melatonin and that patients with both COPD and diabetes may be more susceptible.

Obstructive Sleep Apnea and Longitudinal Changes in Interstitial Lung Imaging and Lung Function: The MESA Study.

Rationale: Obstructive sleep apnea (OSA) has been hypothesized to be a risk factor in interstitial lung disease (ILD) and is associated with radiological markers that may represent the earlier stages of ILD. Prior studies have been limited by their cross-sectional design and potential confounding by body habitus. Objectives: To test the hypothesis that OSA severity is associated with more high-attenuation areas (HAAs) on computed tomography and worse lung function over time among older community-dwelling adults. Methods: We used data from participants in the MESA (Multi-Ethnic Study of Atherosclerosis) who had apnea-hypopnea index (AHI) measured from polysomnography (2010-2013), high attenuation areas (HAAs, -600 to -250 Hounsfield units, n = 784), assessments from exams 5 (2010-2012) and 6 (2016-2018) full-lung computed tomography scans, and spirometry assessments (n = 677). Linear mixed-effects models with random intercept were used to examine associations of OSA severity (i.e., AHI and hypoxic burden) with changes in HAAs, total lung volumes, and forced vital capacity (FVC) between exams 5 and 6. Potential confounders were adjusted for in the model, including age, sex, smoking history, height, and weight. Results: Among those with a higher AHI there were more men and a higher body mass index. Participants with AHI ⩾ 15 events/h and in the highest hypoxic burden quartile each had increases in HAAs of 11.30% (95% confidence interval [CI], 3.74-19.35%) and 9.85% (95% CI, 1.40-19.01%) per 10 years, respectively. There was a more rapid decline in total lung volumes imaged and FVC among those with AHI ⩾ 15 events/h of 220.2 ml (95% CI, 47.8-392.5 ml) and 3.63% (95% CI, 0.43-6.83%) per 10 years, respectively. Conclusions: A greater burden of hypoxia related to obstructive events during sleep was associated with increased lung densities over time and a more rapid decline in lung volumes regardless of body habitus. Our findings suggest OSA may be a contributing factor in the early stages of ILD.

A comparison of mortality rates for buprenorphine versus methadone treatments for opioid use disorder.

OBJECTIVE: Mortality from opioid use disorder (OUD) can be reduced for patients who receive opioid agonist treatment (OAT). In the United States (US), OATs have different requirements including nearly daily visits to a dispensing facility for methadone but weekly to monthly prescriptions for buprenorphine. Our objective was to compare mortality rates for buprenorphine and methadone treatments among a large sample of US patients with OUD. METHODS: We measured all-cause mortality, overdose mortality, and suicide mortality among US Department of Veterans Affairs patients with a diagnosis of OUD who received OAT from 2010 through 2019. We leveraged substantial and sustained regional variation in prescribing buprenorphine versus methadone as an instrumental variable (IV) and used inverse propensity of treatment weighting to balance relevant covariates across treatment groups. We compared mortality with true two-stage IV using both probit and linear probability models, as well as a reduced form IV model, adjusting for demographics and health status. RESULTS: Our cohort consisted of 61,997 patients with OUD who received OAT, of whom 92.7% were male with a mean age of 47.9 (SD = 14.1) years. Patients were followed for a median of 2 (IQR = 1,4) calendar years. Across regional terciles, mean methadone prescribing was 4.8%, 19.5%, and 75.1% of OAT patients. All models identified significant reductions in all-cause and suicide mortality for buprenorphine relative to methadone. For example, predicted all-cause mortality from the probit model was 169.7 per 10,000 person years (95% CI, 157.8, 179.6) in the lowest tercile of methadone prescribing compared with 206.1 (95% CI, 196.0, 216.3) in the highest tercile. No difference was identified for overdose mortality. CONCLUSION: We found significantly lower all-cause mortality and suicide mortality rates for buprenorphine compared with methadone. Our results support the less restrictive prescribing practices for buprenorphine as OAT in the US.

Mortality Patterns Associated with Central Sleep Apnea among Veterans: A Large, Retrospective, Longitudinal Report.

Rationale: Central sleep apnea (CSA) is associated with high mortality. Current knowledge stems from studies with limited sample size (fewer than 100 subjects) and in homogeneous populations such as heart failure (HF). Objectives: To address this knowledge gap, we compared the mortality pattern and time to death between the CSA and obstructive sleep apnea (OSA) patients in the large Veterans Health Administration patient population using the big data analytic approach. Methods: This is a retrospective study using national Veterans Health Administration electronic medical records from October 1, 1999, through September 30, 2020. We grouped the patients with underlying sleep disorders into CSA and OSA, using the International Classification of Diseases, Ninth and Tenth Revision codes. We applied Cox regression analysis to compare the mortality rate and hazard ratio (HR) among the two groups and adjusted HR by gender, race, body mass index (BMI), age, and Charlson Comorbidity Index. In CSA groups, a machine-learning algorithm was used to determine the most important predictor of time to death. Further subgroup analysis was also performed in patients that had comorbid HF. Results: Evaluation of patients resulted in 2,961 grouped as CSA and 1,487,353 grouped as OSA. Patients with CSA were older (61.8 ± 15.6 yr) than those with OSA (56.7 ± 13.9 yr). A higher proportion of patients with CSA (25.1%) died during the study period compared with the OSA cohort (14.9%). The adjusted HR was 1.53 (95% confidence interval [CI], 1.43-4.65). Presence of HF history of cerebrovascular disease, hemiplegia, and having a BMI less than 18.5 were among the highest predictors of mortality in CSA. The subgroup analysis revealed that the presence of HF was associated with increased mortality both in CSA (HR, 7.4; 95% CI, 6.67-8.21) and OSA (HR, 4.3; 95% CI, 4.26-4.34) groups. Conclusions: Clinically diagnosed CSA was associated with a shorter time to death from the index diagnostic date. Almost one-fifth of patients with CSA died within 5 years of diagnosis. The presence of HF, history of cerebrovascular disease and hemiplegia, male sex, and being underweight were among the highest predictors of mortality in CSA. CSA was associated with higher mortality than OSA, independent of associated comorbidity.

International Consensus Statement on Obstructive Sleep Apnea.

BACKGROUND: Evaluation and interpretation of the literature on obstructive sleep apnea (OSA) allows for consolidation and determination of the key factors important for clinical management of the adult OSA patient. Toward this goal, an international collaborative of multidisciplinary experts in sleep apnea evaluation and treatment have produced the International Consensus statement on Obstructive Sleep Apnea (ICS:OSA). METHODS: Using previously defined methodology, focal topics in OSA were assigned as literature review (LR), evidence-based review (EBR), or evidence-based review with recommendations (EBR-R) formats. Each topic incorporated the available and relevant evidence which was summarized and graded on study quality. Each topic and section underwent iterative review and the ICS:OSA was created and reviewed by all authors for consensus. RESULTS: The ICS:OSA addresses OSA syndrome definitions, pathophysiology, epidemiology, risk factors for disease, screening methods, diagnostic testing types, multiple treatment modalities, and effects of OSA treatment on multiple OSA-associated comorbidities. Specific focus on outcomes with positive airway pressure (PAP) and surgical treatments were evaluated. CONCLUSION: This review of the literature consolidates the available knowledge and identifies the limitations of the current evidence on OSA. This effort aims to create a resource for OSA evidence-based practice and identify future research needs. Knowledge gaps and research opportunities include improving the metrics of OSA disease, determining the optimal OSA screening paradigms, developing strategies for PAP adherence and longitudinal care, enhancing selection of PAP alternatives and surgery, understanding health risk outcomes, and translating evidence into individualized approaches to therapy.