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.

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.

Cardiovascular Benefit of Continuous Positive Airway Pressure in Adults with Coronary Artery Disease and Obstructive Sleep Apnea without Excessive Sleepiness.

Rationale: Randomized controlled trials of continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA) have not demonstrated protection against adverse cardiovascular outcomes. Recently, observational studies revealed that OSA-related cardiovascular risk is concentrated in patients with an elevated pulse rate response to respiratory events (ΔHR). Objectives: Here, in this post hoc analysis of a prospective clinical trial, we test the hypothesis that a greater pretreatment ΔHR is associated with greater CPAP-related protection against adverse cardiovascular outcomes. Methods: ΔHR was measured from baseline polysomnography of the RICCADSA (Randomized Intervention with CPAP in CAD and OSA) randomized controlled trial (patients with coronary artery disease [CAD] and OSA [apnea-hypopnea index ⩾ 15 events/h] with Epworth Sleepiness Scale score < 10; nCPAP:ncontrol = 113:113; male, 85%; age, 66 ± 8 [mean ± SD] yr). The primary outcome was a composite of repeat revascularization, myocardial infarction, stroke, and cardiovascular mortality. Multivariable Cox regression assessed whether the effect of CPAP was moderated by ΔHR (treatment-by-ΔHR interaction). Measurements and Main Results: The CPAP-related reduction in risk increased progressively with increasing pretreatment ΔHR (interaction hazard ratio [95% confidence interval], 0.49 [0.27 to 0.90] per SD increase in ΔHR; P < 0.05). This means that in patients with a ΔHR of 1 SD above the mean (i.e., 10 beats/min), CPAP was estimated to reduce cardiovascular risk by 59% (6% to 82%) (P < 0.05), but no significant risk reduction was estimated in patients with a mean ΔHR (6 beats/min; CPAP risk reduction, 16% [-53% to 54%]; P = 0.6). Conclusions: The protective effect of CPAP in patients with CAD and OSA without excessive sleepiness was modified by the ΔHR. Specifically, patients with higher ΔHR exhibit greater cardiovascular benefit from CPAP therapy.

Targeted Genome Sequencing Identifies Multiple Rare Variants in Caveolin-1 Associated with Obstructive Sleep Apnea.

Rationale: Obstructive sleep apnea (OSA) is a common disorder associated with increased risk for cardiovascular disease, diabetes, and premature mortality. There is strong clinical and epidemiologic evidence supporting the importance of genetic factors influencing OSA but limited data implicating specific genes. Objectives: To search for rare variants contributing to OSA severity. Methods: Leveraging high-depth genomic sequencing data from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program and imputed genotype data from multiple population-based studies, we performed linkage analysis in the CFS (Cleveland Family Study), followed by multistage gene-based association analyses in independent cohorts for apnea-hypopnea index (AHI) in a total of 7,708 individuals of European ancestry. Measurements and Main Results: Linkage analysis in the CFS identified a suggestive linkage peak on chromosome 7q31 (LOD = 2.31). Gene-based analysis identified 21 noncoding rare variants in CAV1 (Caveolin-1) associated with lower AHI after accounting for multiple comparisons (P = 7.4 × 10-8). These noncoding variants together significantly contributed to the linkage evidence (P < 10-3). Follow-up analysis revealed significant associations between these variants and increased CAV1 expression, and increased CAV1 expression in peripheral monocytes was associated with lower AHI (P = 0.024) and higher minimum overnight oxygen saturation (P = 0.007). Conclusions: Rare variants in CAV1, a membrane-scaffolding protein essential in multiple cellular and metabolic functions, are associated with higher CAV1 gene expression and lower OSA severity, suggesting a novel target for modulating OSA severity.

Sequencing Analysis at 8p23 Identifies Multiple Rare Variants in DLC1 Associated with Sleep-Related Oxyhemoglobin Saturation Level.

Average arterial oxyhemoglobin saturation during sleep (AvSpO2S) is a clinically relevant measure of physiological stress associated with sleep-disordered breathing, and this measure predicts incident cardiovascular disease and mortality. Using high-depth whole-genome sequencing data from the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) project and focusing on genes with linkage evidence on chromosome 8p23,1,2 we observed that six coding and 51 noncoding variants in a gene that encodes the GTPase-activating protein (DLC1) are significantly associated with AvSpO2S and replicated in independent subjects. The combined DLC1 association evidence of discovery and replication cohorts reaches genome-wide significance in European Americans (p = 7.9 × 10-7). A risk score for these variants, built on an independent dataset, explains 0.97% of the AvSpO2S variation and contributes to the linkage evidence. The 51 noncoding variants are enriched in regulatory features in a human lung fibroblast cell line and contribute to DLC1 expression variation. Mendelian randomization analysis using these variants indicates a significant causal effect of DLC1 expression in fibroblasts on AvSpO2S. Multiple sources of information, including genetic variants, gene expression, and methylation, consistently suggest that DLC1 is a gene associated with AvSpO2S.

Using a mixed-effect model with a parameter-space of heterogenous dimension to evaluate whether accountable care organizations are associated with greater uniformity across constituent practices.

Accountable care organization (ACO) legislation was designed to improve patient outcomes by inducing greater coordination of care and adoption of best practices. Therefore, it is of interest to assess whether greater uniformity occurs among practices comprising an ACO post ACO formation. We develop a mixed-effect model with a difference-in-difference design to evaluate the effect of a patient receiving care from an ACO on patient outcomes and adapt this model to examine whether an ACO is associated with increased uniformity across its constituent practices. The task is complicated by the organizations within an ACO forming an additional layer in the multilevel model, due to medical practices and hospitals that form an ACOs being nested within the ACO, making the number of levels of the model variable and the dimension of the parameter space time-varying. We develop the model and a procedure for testing the hypothesis that ACO formation was associated with increased uniformity among its constituent practices. We apply our procedure to a cohort of medicare beneficiaries followed over 2009-2014. Although there is extensive heterogeneity of becoming an ACOs across practices, we find that the formation of an ACO appears to be associated with greater uniformity of patient outcomes among its constituent practices.

The Sleep Apnea-Specific Pulse-Rate Response Predicts Cardiovascular Morbidity and Mortality.

Rationale: Randomized controlled trials have been unable to detect a cardiovascular benefit of continuous positive airway pressure in unselected patients with obstructive sleep apnea (OSA). We hypothesize that deleterious cardiovascular outcomes are concentrated in a subgroup of patients with a heightened pulse-rate response to apneas and hypopneas (ΔHR). Methods: We measured the ΔHR in the MESA (Multi-Ethnic Study of Atherosclerosis) (N = 1,395) and the SHHS (Sleep Heart Health Study) (N = 4,575). MESA data were used to determine the functional form of the association between the ΔHR and subclinical cardiovascular biomarkers, whereas primary analyses tested the association of the ΔHR with nonfatal or fatal cardiovascular disease (CVD) and all-cause mortality in longitudinal data from the SHHS. Measurements and Main Results: In the MESA, U-shaped relationships were observed between subclinical CVD biomarkers (coronary artery calcium, NT-proBNP [N-terminal prohormone BNP], and Framingham risk score) and the ΔHR; notably, a high ΔHR (upper quartile) was associated with elevated biomarker scores compared with a midrange ΔHR (25th-75th centiles). In the SHHS, individuals with a high ΔHR compared with a midrange ΔHR were at increased risk of nonfatal or fatal CVD and all-cause mortality (nonfatal adjusted hazard ratio [95% confidence interval (CI)], 1.60 [1.28-2.00]; fatal adjusted hazard ratio [95% CI], 1.68 [1.22-2.30]; all-cause adjusted hazard ratio [95% CI], 1.29 [1.07-1.55]). The risk associated with a high ΔHR was particularly high in those with a substantial hypoxic burden (nonfatal, 1.93 [1.36-2.73]; fatal, 3.50 [2.15-5.71]; all-cause, 1.84 [1.40-2.40]) and was exclusively observed in nonsleepy individuals. Conclusions: Individuals with OSA who demonstrate an elevated ΔHR are at increased risk of cardiovascular morbidity and mortality. This study identifies a prognostic biomarker for OSA that appears useful for risk stratification and patient selection for future clinical trials.

Is It Time for the Mental Health Field to Consider Unplanned Discharge a Key Metric of Patient Safety?

ABSTRACT: Mental health lacks robust measures to assess patient safety. Unplanned discharge is common in mental health populations and associated with poor outcomes. Clarifying whether unplanned discharge varies across settings may highlight the need to develop measures to reduce harms associated with this event. Unplanned discharge rates were compared across the Department of Veterans Affairs' acute inpatient and residential mental health treatment settings from 2009 to 2019. Logistic regression was used to create facility-level, adjusted unplanned discharge rates stratified by setting. Results were described using central tendency. Among 847,661 acute inpatient discharges, the mean unplanned discharge rate was 3.3% (range, 0%-18%). Among 358,117 residential discharges, the mean unplanned discharge rate was 17.9% (range, 1%-48.3%). Unplanned discharge is a marked problem in mental health, with large variation across treatment settings. Unplanned discharge should be measured as part of patient safety efforts.

Associations of variants In the hexokinase 1 and interleukin 18 receptor regions with oxyhemoglobin saturation during sleep.

Sleep disordered breathing (SDB)-related overnight hypoxemia is associated with cardiometabolic disease and other comorbidities. Understanding the genetic bases for variations in nocturnal hypoxemia may help understand mechanisms influencing oxygenation and SDB-related mortality. We conducted genome-wide association tests across 10 cohorts and 4 populations to identify genetic variants associated with three correlated measures of overnight oxyhemoglobin saturation: average and minimum oxyhemoglobin saturation during sleep and the percent of sleep with oxyhemoglobin saturation under 90%. The discovery sample consisted of 8,326 individuals. Variants with p < 1 × 10(-6) were analyzed in a replication group of 14,410 individuals. We identified 3 significantly associated regions, including 2 regions in multi-ethnic analyses (2q12, 10q22). SNPs in the 2q12 region associated with minimum SpO2 (rs78136548 p = 2.70 × 10(-10)). SNPs at 10q22 were associated with all three traits including average SpO2 (rs72805692 p = 4.58 × 10(-8)). SNPs in both regions were associated in over 20,000 individuals and are supported by prior associations or functional evidence. Four additional significant regions were detected in secondary sex-stratified and combined discovery and replication analyses, including a region overlapping Reelin, a known marker of respiratory complex neurons.These are the first genome-wide significant findings reported for oxyhemoglobin saturation during sleep, a phenotype of high clinical interest. Our replicated associations with HK1 and IL18R1 suggest that variants in inflammatory pathways, such as the biologically-plausible NLRP3 inflammasome, may contribute to nocturnal hypoxemia.

Insomnia symptom severity and cognitive performance: Moderating role of APOE genotype.

INTRODUCTION: We evaluated whether insomnia symptom severity was associated with cognitive function, and whether this relationship was modified by biomarkers associated with Alzheimer's disease risk. METHODS: We examined insomnia symptoms and neuropsychological performance 3.4 years later in 511 dementia-free Framingham Heart Study participants (62.65 ± 8.7 years, 50.9% male). Additionally, we explored insomnia symptoms combined with self-reported short habitual sleep duration and effect modification by apolipoprotein E (APOE) ε4 allele status. RESULTS: More severe insomnia symptoms were associated with lower performance on global cognition, and immediate and delayed Logical Memory recall, especially when insomnia symptoms were combined with short sleep duration. The association between insomnia symptoms and poorer memory recall was more pronounced in APOE ε4 allele carriers. DISCUSSION: Insomnia symptom severity was associated with worse subsequent global cognitive and memory performance, which was especially apparent in APOE ε4 allele carriers, suggesting that poor sleep might be particularly detrimental when the brain is already vulnerable to neurodegeneration.

Admixture mapping identifies novel loci for obstructive sleep apnea in Hispanic/Latino Americans.

Obstructive sleep apnea (OSA) is a common disorder associated with increased risk of cardiovascular disease and mortality. Its prevalence and severity vary across ancestral background. Although OSA traits are heritable, few genetic associations have been identified. To identify genetic regions associated with OSA and improve statistical power, we applied admixture mapping on three primary OSA traits [the apnea hypopnea index (AHI), overnight average oxyhemoglobin saturation (SaO2) and percentage time SaO2 < 90%] and a secondary trait (respiratory event duration) in a Hispanic/Latino American population study of 11 575 individuals with significant variation in ancestral background. Linear mixed models were performed using previously inferred African, European and Amerindian local genetic ancestry markers. Global African ancestry was associated with a lower AHI, higher SaO2 and shorter event duration. Admixture mapping analysis of the primary OSA traits identified local African ancestry at the chromosomal region 2q37 as genome-wide significantly associated with AHI (P < 5.7 × 10-5), and European and Amerindian ancestries at 18q21 suggestively associated with both AHI and percentage time SaO2 < 90% (P < 10-3). Follow-up joint ancestry-SNP association analyses identified novel variants in ferrochelatase (FECH), significantly associated with AHI and percentage time SaO2 < 90% after adjusting for multiple tests (P < 8 × 10-6). These signals contributed to the admixture mapping associations and were replicated in independent cohorts. In this first admixture mapping study of OSA, novel associations with variants in the iron/heme metabolism pathway suggest a role for iron in influencing respiratory traits underlying OSA.

Sleep Apnea and Cardiovascular Disease.

PURPOSE OF REVIEW: Obstructive sleep apnea (OSA) is associated with incident coronary and cerebral vascular disease. The mechanisms underlying this association are thought to include increased sympathetic nervous system activity, oxidative stress, and systemic inflammation, with these effects mediated in part by elevated blood pressure and impaired glucose metabolism. In observational studies, OSA treatment with positive airway pressure (PAP) is associated with a reduction in cardiovascular disease risk. The aim of this review is to evaluate evidence from recent clinical trials that tested the impact of OSA treatment on major cardiovascular disease outcomes. RECENT FINDINGS: Multicenter randomized trials have demonstrated a significant, albeit modest, reduction in blood pressure with OSA treatment. Treatment of OSA has generally not demonstrated improvement in type 2 diabetes mellitus, although limited evidence suggests that treatment may be effective in the prediabetic period. However, recent randomized trials of PAP treatment for OSA failed to demonstrate a reduction in incident or recurrent cardiovascular disease events. This may reflect the enrollment of a mostly non-sleepy study sample, as recent evidence suggests that sleepiness is a predictor of adverse cardiovascular outcomes from OSA. PAP treatment of OSA lowers blood pressure and may improve glucose metabolism; however, randomized clinical trials do not indicate a reduction in cardiovascular risk with treatment of minimally symptomatic OSA patients.

Interhemispheric sleep depth coherence predicts driving safety in sleep apnea.

Obstructive sleep apnea is associated with increased risk of car crashes; however, conventional measures of sleep apnea severity do not clearly identify those individuals who are at greatest risk. Here we tested whether, among individuals with sleep apnea, those with reduced interhemispheric sleep depth coherence, measured by correlation between right and left hemisphere odds ratio product, are at greater risk. The sample was derived from the Sleep Heart Health Study, a prospective observational cohort study, and included 1,378 adults with sleep apnea. The occurrence of a car crash was ascertained by a questionnaire administered 2 years after the sleep study, which asked about the occurrence of crashes during the year prior to questionnaire administration. We computed the sleep depth coherence from electroencephalograms recorded during baseline sleep studies and after 5 years. The weighted kappa coefficient and Bangdiwala's B were 0.34 and 0.59, respectively, indicating a fair to moderate stability over a 5-year interval. Multivariate logistic regression, adjusted for age, sex, race, body mass index and miles driven per year, was used to assess the risk of a car crash. Compared to the lowest quartile of sleep depth coherence (<0.86), individuals in the highest quartile (>0.93) had a 62% (95% confidence interval, 22%-81%) lower risk of an accident. Further adjustments for usual sleep duration and sleepiness did not meaningfully alter these findings. Higher interhemispheric sleep depth coherence is associated with significantly lower risk of motor vehicle crashes in individuals with sleep apnea. This suggests that high interhemispheric sleep depth coherence may be a marker of resistance to sleep apnea-related adverse neurocognitive outcomes.

Effects of continuous positive airway pressure on blood pressure in obstructive sleep apnea patients: The Apnea Positive Pressure Long-term Efficacy Study (APPLES).

Obstructive sleep apnea is associated with hypertension, and short-term studies have demonstrated a modest reduction in blood pressure with continuous positive airway pressure therapy. We evaluated the effects of continuous positive airway pressure versus sham continuous positive airway pressure on blood pressure in 1,101 participants with obstructive sleep apnea from the Apnea Positive Pressure Long-term Efficacy Study, a randomized, sham-controlled double-blinded study designed to assess the impact of continuous positive airway pressure on neurocognition. Participants with apnea-hypopnea index ≥ 10 were randomly assigned to continuous positive airway pressure or sham continuous positive airway pressure. Blood pressures measured in the morning and evening at baseline, 2 months and 6 months were analysed post hoc using a mixed-model repeated-measures analysis of variance. The largest magnitude reduction was approximately 2.4 mmHg in morning systolic pressure that occurred at 2 months in the continuous positive airway pressure arm as compared with an approximate 0.5 mmHg reduction in the sham group (continuous positive airway pressure effect -1.9 mmHg, p = .008). At 6 months, the difference between groups was diminished and no longer statistically significant (continuous positive airway pressure effect -0.9 mmHg, p = .12). Sensitivity analysis with use of multiple imputation approaches to account for missing data did not change the results. Treatment with continuous positive airway pressure for obstructive sleep apnea reduces morning but not evening blood pressure in a population with well-controlled blood pressure. The effect was greater after 2 than after 6 months of treatment.

Symptom Subtypes of Obstructive Sleep Apnea Predict Incidence of Cardiovascular Outcomes.

Rationale: Symptom subtypes have been described in clinical and population samples of patients with obstructive sleep apnea (OSA). It is unclear whether these subtypes have different cardiovascular consequences.Objectives: To characterize OSA symptom subtypes and assess their association with prevalent and incident cardiovascular disease in the Sleep Heart Health Study.Methods: Data from 1,207 patients with OSA (apnea-hypopnea index ≥ 15 events/h) were used to evaluate the existence of symptom subtypes using latent class analysis. Associations between subtypes and prevalence of overall cardiovascular disease and its components (coronary heart disease, heart failure, and stroke) were assessed using logistic regression. Kaplan-Meier survival analysis and Cox proportional hazards models were used to evaluate whether subtypes were associated with incident events, including cardiovascular mortality.Measurements and Main Results: Four symptom subtypes were identified (disturbed sleep [12.2%], minimally symptomatic [32.6%], excessively sleepy [16.7%], and moderately sleepy [38.5%]), similar to prior studies. In adjusted models, although no significant associations with prevalent cardiovascular disease were found, the excessively sleepy subtype was associated with more than threefold increased risk of prevalent heart failure compared with each of the other subtypes. Symptom subtype was also associated with incident cardiovascular disease (P < 0.001), coronary heart disease (P = 0.015), and heart failure (P = 0.018), with the excessively sleepy again demonstrating increased risk (hazard ratios, 1.7-2.4) compared with other subtypes. When compared with individuals without OSA (apnea-hypopnea index < 5), significantly increased risk for prevalent and incident cardiovascular events was observed mostly for patients in the excessively sleepy subtype.Conclusions: OSA symptom subtypes are reproducible and associated with cardiovascular risk, providing important evidence of their clinical relevance.

Electroconvulsive Therapy in Veterans Health Administration Hospitals: Prevalence, Patterns of Use, and Patient Characteristics.

OBJECTIVES: The body of large-scale, epidemiological research on electroconvulsive therapy (ECT) in the United States is limited. To address this gap, we assessed demographic, clinical, pharmacological, and mental health treatment history as well as 2-year mortality outcomes associated with ECT use in the largest U.S. health care system. METHODS: Among all patients who sought mental health care at Veterans Health Administration (VHA) hospitals in 2012, we used bivariate analyses to compare patients who did and not receive ECT during 2 years of follow-up. Among the population who received ECT, descriptive statistics were calculated to characterize prior mental health treatment patterns and ECT receipt. RESULTS: 0.11% (N = 1616) of all VHA mental health patients in 2012 (N = 1,457,053) received ECT in 2 years of follow-up. There was significant regional variation in provision of ECT. Those who received ECT were more likely to have diagnoses of major depressive, bipolar, and personality disorders and were significantly more likely to have had a recent mental health inpatient stay (risk ratio, 6.94). Receipt of ECT was not associated with a difference in all-cause mortality (risk ratio, 0.88). Thirty-two percent of those who received ECT had no substantial antidepressant or therapy trial in the year before index mental health encounter. CONCLUSIONS: Use of ECT in the VHA is rare. Patients who receive ECT have a complex and high-risk profile, not necessarily consistent with the most common indications for ECT.

Diagnosis and Management of Obstructive Sleep Apnea: A Review.

Importance: Obstructive sleep apnea (OSA) affects 17% of women and 34% of men in the US and has a similar prevalence in other countries. This review provides an update on the diagnosis and treatment of OSA. Observations: The most common presenting symptom of OSA is excessive sleepiness, although this symptom is reported by as few as 15% to 50% of people with OSA in the general population. OSA is associated with a 2- to 3-fold increased risk of cardiovascular and metabolic disease. In many patients, OSA can be diagnosed with home sleep apnea testing, which has a sensitivity of approximately 80%. Effective treatments include weight loss and exercise, positive airway pressure, oral appliances that hold the jaw forward during sleep, and surgical modification of the pharyngeal soft tissues or facial skeleton to enlarge the upper airway. Hypoglossal nerve stimulation is effective in select patients with a body mass index less than 32. There are currently no effective pharmacological therapies. Treatment with positive airway pressure lowers blood pressure, especially in patients with resistant hypertension; however, randomized clinical trials of OSA treatment have not demonstrated significant benefit on rates of cardiovascular or cerebrovascular events. Conclusions and Relevance: OSA is common and the prevalence is increasing with the increased prevalence of obesity. Daytime sleepiness is among the most common symptoms, but many patients with OSA are asymptomatic. Patients with OSA who are asymptomatic, or whose symptoms are minimally bothersome and pose no apparent risk to driving safety, can be treated with behavioral measures, such as weight loss and exercise. Interventions such as positive airway pressure are recommended for those with excessive sleepiness and resistant hypertension. Managing asymptomatic OSA to reduce cardiovascular and cerebrovascular events is not currently supported by high-quality evidence.

Associations between Medication Assisted Therapy Services Delivery and Mortality in a National Cohort of Veterans with Posttraumatic Stress Disorder and Opioid Use Disorder.

Objective: Opioid use disorder (OUD) is a notable concern in the United States (US) and strongly associated with mortality. There is a high prevalence of OUD in patients with posttraumatic stress disorder (PTSD) and the mortality associated with OUD may be exacerbated in patients with PTSD. Medication-assisted treatment (MAT) for OUD has become standard of care for OUD and has been shown to reduce mortality. However, there has been little study of MAT and mortality in patients with PTSD and OUD. Methods: We conducted a retrospective cohort study in U.S. veterans who had newly engaged in PTSD treatment, were diagnosed with OUD and were provided MAT for at least one day between 2004 and 2013. We assessed mortality for one year following the index diagnosis date. We calculated all-cause mortality as well as death by external cause, overdose plus suicide, overdose, and suicide rates per 100,000. We used hazard ratios (HR) and 95% confidence intervals (CI) to compare death rates between patients with high versus low adherence to MAT. We evaluated the impact of high versus low exposure to general substance abuse care. We considered a confidence interval that did not cross one to be significant. Results: A total of 5,901 patients met inclusion criteria. Most patients were men and the average age was 43.3 years (SD = 13.8). The all-cause mortality rate was 1,370 per 100,000 patients. High adherence to MAT resulted in a non-significant, decreased risk for death due to all-cause (HR = 0.73, 95% CI [0.47, 1.13]), external cause (HR = 0.71, 95% CI [0.38, 1.35]), and overdose or suicide (HR = 0.66, 95% CI [0.33, 1.35]). Patients with high exposure (≥ 60 days) to general substance abuse care were significantly less likely to die due to external cause (HR = 0.39, 95% CI [0.18, 0.85]) and overdose or suicide (HR = 0.31, 95% CI [0.12, 0.77]). Conclusions: In patients with PTSD and OUD, improved adherence to MAT and greater exposure to general substance abuse care may result in lower mortality. Studies with longer follow-up and larger sample sizes to assess the impact of MAT on suicide are needed to confirm our findings.

Developing and Validating a Measure to Estimate Poverty in Medicare Administrative Data.

OBJECTIVE: To develop and validate a measure that estimates individual level poverty in Medicare administrative data that can be used in studies of Medicare claims. DATA SOURCES: A 2008 to 2013 Medicare Current Beneficiary Survey linked to 2008 to 2013 Medicare fee-for-service beneficiary summary file and census data. STUDY DESIGN AND METHODS: We used the Medicare Current Beneficiary Survey to define individual level poverty status and linked to Medicare administrative data (N=38,053). We partitioned data into a measure derivation dataset and a validation dataset. In the derivation data, we used a logistic model to regress poverty status on measures of dual eligible status, part D low-income subsidy, and demographic and administrative data, and modeled with and without linked census and nursing home data. Each beneficiary receives a predicted poverty score from the model. Performance was evaluated in derivation and validation data and compared with other measures used in the literature. We present a measure for income-only poverty as well as one for income and asset poverty. PRINCIPAL FINDINGS: A score (predicted probability of income poverty) >0.5 yielded 58% sensitivity, 94% specificity, and 84% positive predictive value in the derivation data; our score yielded very similar results in the validation data. The model's c-statistic was 0.84. Our poverty score performed better than Medicaid enrollment, high zip code poverty, and zip code median income. The income and asset version performed similarly well. CONCLUSIONS: A poverty score can be calculated using Medicare administrative data for use as a continuous or binary measure. This measure can improve researchers' ability to identify poverty in Medicare administrative data.

Changes in Use of Postacute Care Associated With Accountable Care Organizations in Hip Fracture, Stroke, and Pneumonia Hospitalized Cohorts.

OBJECTIVE: To examine changes in more and less discretionary condition-specific postacute care use (skilled nursing, inpatient rehabilitation, home health) associated with Medicare accountable care organization (ACO) implementation. DATA SOURCES: 2009-2014 Medicare fee-for-service claims. STUDY DESIGN: Difference-in-difference methodology comparing postacute outcomes after hospitalization for hip fracture and stroke (where rehabilitation is fundamental to the episode of care) to pneumonia, (where it is more discretionary) for beneficiaries attributed to ACO and non-ACO providers. PRINCIPAL FINDINGS: Across all 3 cohorts, in the baseline period ACO patients were more likely to receive Medicare-paid postacute care and had higher episode spending. In hip fracture patients where rehabilitation is standard of care, ACO implementation was associated with 6%-8% increases in probability of admission to a skilled nursing facility or inpatient rehabilitation (compared with home without care), and a slight reduction in readmissions. In a clinical condition where rehabilitation is more discretionary, pneumonia, ACO implementation was not associated with changes in postacute location, but episodic spending decreased 2%-3%. Spending decreases were concentrated in the least complex patients. Across all cohorts, the length of stay in skilled nursing facilities decreased with ACO implementation. CONCLUSIONS: ACOs decreased spending on postacute care by decreasing use of discretionary services. ACO implementation was associated with reduced length of stay in skilled nursing facilities, while hip fracture patients used institutional postacute settings at higher rates. Among pneumonia patients, we observed decreases in spending, readmission days, and mortality associated with ACO implementation.