Long-term mortality in ischemic stroke patients with concomitant chronic obstructive pulmonary disease.

BACKGROUND: Long-term mortality in ischemic stroke patients with concomitant COPD has been largely unexplored. This study aimed to compare long-term all-cause mortality in ischemic stroke patients with and without COPD. METHODS: This was a retrospective cohort study of ischemic stroke patients with and without COPD in the Geisinger Neuroscience Ischemic Stroke database to examine all-cause mortality up to 3 years using Kaplan-Meier estimator and Cox proportional hazards model. RESULTS: Of the 6,589 ischemic stroke patients included in this study, 5,525 (83.9%) did not have COPD (group A). Group B (n=1,006) consisted of patients with COPD diagnosis by ICD-9/10-CM codes. COPD patients in Group C (n=233) were diagnosed by spirometry, and in Group D (n=175) by both ICD-9/10-CM codes and spirometry confirmation. The survival probabilities at three years in Group B, C, and D were significantly lower than in Group A. Group B (HR=1.262, 95% CI 1.122-1.42, p<0.001) and group C (HR=1.251, 95% CI 1.01-1.55, p=0.041) had significantly lower hazard of mortality compared to group A. There was no significant difference in survival between COPD subtypes of chronic bronchitis and emphysema. Patients in Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2 stage had an increased mortality hazard compared to the GOLD 1 stage. CONCLUSIONS: While ischemic stroke patients with preexisting COPD have worse long-term survival than those without COPD, the results largely depended on the definition of COPD used. These results suggest that ischemic stroke patients with COPD need more personalized medical care to decrease long-term mortality.

Neutrophil-to-lymphocyte ratio decreases in obstructive sleep apnea treated with mandibular advancement devices.

PURPOSE: Obstructive sleep apnea has been associated with chronic inflammation triggered by nocturnal hypoxemia. The neutrophil-to-lymphocyte ratio (NLR) is a measure of subclinical systemic inflammation. We hypothesize that NLR levels would improve as chronic inflammation diminishes in obstructive sleep apnea (OSA) patients treated with mandibular advancement devices (MADs). METHODS: We studied patients with OSA who were treated with MAD as a first-line treatment or because they could not tolerate CPAP. We obtained pre-treatment and post-treatment complete blood counts. NLR was calculated by dividing the number of neutrophils by the number of lymphocytes obtained from the CBCs. Patients with other conditions known to affect NLR were excluded from the study. RESULTS: We compared the values of NLR and oxygen desaturation index (ODI) before and after treatment with MAD in 22 patients who met inclusion criteria and completed the study protocol. There was a significant difference in NLR before and after treatment (p = 0.01). There was also a significant difference in the 3% ODI and 4% ODI before and after treatment with MAD (p = 0.014, 0.007), respectively. A subgroup analysis compared NLR in two groups of patients, the optimally treated and suboptimally treated. There was a significant decrease in the NLR in the optimally treated group (n = 10) (p < 0.01), whereas it did not change in the suboptimally treated group (n = 12) (p = 0.349). CONCLUSION: The neutrophil-to-lymphocyte ratio may be useful in documenting improvement in inflammation for OSA patients treated with mandibular advancement devices. Our results specifically suggest that the NLR values are associated with the decrease in the ODI.

Idiopathic Hypersomnia: Neurobiology, Diagnosis, and Management.

Idiopathic hypersomnia is a chronic neurologic sleep disorder that manifests as excessive daytime sleepiness despite normal or prolonged sleep times for age. Frequently, idiopathic hypersomnia is clinically characterized by marked sleep inertia, long and unrefreshing naps, and a high sleep efficiency. Since the initial description, there has been an ongoing evolution of its nomenclature, approach to diagnosis, characterization of symptoms, and determination of the burden of disease. In addition, an increased attention to and study of its epidemiology, neurobiology, and potential therapeutic strategies has begun to contribute to a better approach to identifying and treating it. At present, idiopathic hypersomnia is considered an orphan disease with unknown frequency and the cause is unknown; however, there is evidence to suggest circadian and sleep structure differences, structural brain changes, and neurochemical changes may contribute to the development and expression of this disease. The approach to treatment can be challenging owing to a limited number of approved treatments (calcium, magnesium, potassium, and sodium oxybates) in idiopathic hypersomnia. However, consideration of therapies shown to improve excessive daytime sleepiness in other disorders is frequently employed. Future directions require a clear consensus on the defining characteristics of idiopathic hypersomnia to enhance the opportunity for improved recognition, diagnosis, and treatment strategies to be established. This article provides a historical review of the evolving diagnostic classification of idiopathic hypersomnia, potential insights to the underlying pathophysiology, and a summary of proposed approaches for diagnosis and therapeutic intervention.

An overview of noninvasive ventilation in cystic fibrosis.

Noninvasive ventilation (NIV) use was initially reported in cystic fibrosis (CF) in 1991 as a bridge to lung transplantation, and over the decades, the use of NIV has increased in the CF population. Individuals with CF are prone to various physiologic changes as lung function worsens, and they benefit from NIV for advanced lung disease. As life expectancy in CF has been increasing due to advances such as highly effective modulator therapy, people with CF may also benefit from NIV for other diagnosis beyond advanced lung disease. NIV can improve gas exchange, quality of sleep, exercise tolerance, and augment airway clearance in CF. CF providers can readily become comfortable with this therapeutic modality. In this review, we will summarize the physiologic basis for NIV use in CF, describe indications for initiation, and discuss how to order and monitor patients on NIV. We will discuss aspects unique to people with CF and the use of NIV, as well as suggestions on how to reduce risks such as infection. We hope that this serves as a resource for CF providers, in particular those who do not have dedicated training in sleep medicine as we all continue to care for the CF patient population.

Centers for Medicare and Medicaid Services Positive Airway Pressure Adherence Criteria May Limit Treatment to Many Medicare Beneficiaries.

STUDY OBJECTIVES: Centers for Medicare and Medicaid Services (CMS) reimbursement for positive airway pressure (PAP) devices for obstructive sleep apnea treatment is dependent on patients meeting adherence expectations within the first 3 months on therapy. Adherence is defined as usage of the device for at least 4 hours per night on 70% of nights during a consecutive 30-day period. We hypothesize that the adherence pattern may be established beyond this initial period, which may limit the opportunity to treat many patients. METHODS: Treatment and adherence data from PAP devices were monitored via wireless modems for 42 consecutive PAP-naïve military veterans who completed 1 year of nightly monitoring. Their baseline characteristics were as follows: age (mean ± standard deviation) 58.5 ± 12.5 years; body mass index 33.7 ± 5.7 kg/m2; diagnostic apnea-hypopnea index (pretreatment) 28.1 ± 18.5 events/h; apnea-hypopnea index on PAP: 4.3 ± 3.3 events/h. We examined daily, monthly, quarterly, semiannual, and annual reports, and the best 30-day adherence report for each quarter. RESULTS: In the first 3 months, 19 of 42 participants were adherent by CMS criteria, and 23 of 42 participants were not. Of the 19 adherent participants, 13 remained adherent and 6 became nonadherent or stopped PAP treatment for the remainder of the year. In the 23 initially nonadherent participants, 16 stopped PAP treatment, and 7 participants (30.4%) became adherent (using CMS criteria) during the rest of the year. Thus, PAP adherence during the first 3 months was predictive for the rest of the year in only 68.4%. PAP nonadherence during the first 3 months was predictive for further nonadherence in only 69.6% of the cases. Overall, this led to a 65% sensitivity and 72% specificity of using adherence at 3 months in predicting adherence at 1 year. CONCLUSIONS: CMS adherence criteria affecting PAP coverage are restrictive and can result in the withholding of therapy in many patients who otherwise might become adherent. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov, Title: Remote Monitoring in Obstructive Sleep Apnea, Identifier: NCT01678560, URL: https:// clinicaltrials.gov/ct2/show/NCT01678560.

Estimation of adaptive ventilation success and failure using polysomnogram and outpatient therapy biomarkers.

Study Objectives: Adaptive servo-ventilation (ASV) devices provide anticyclic pressure support for the treatment of central and/or complex sleep apnea, including heart failure patients. Variability in responses in the clinic and negative clinical trials motivated assessment of standard and novel signal biomarkers for ASV efficacy. Methods: Multiple clinical databases were queried to assess potential signal biomarkers of ASV effectiveness, including the following: (1) attended laboratory adaptive ventilation titrations: 108, of which 66 had mainstream ETCO2 measurements; (2) AirView data in 98 participants, (3) complete data, from diagnostic polysomnogram (PSG) through review and prospective analysis of on-therapy data using SleepyHead freeware in 44 participants; and (4) hemodynamic data in the form of beat-to-beat blood pressure during ASV titration, using a Finometer in five participants. Results: Signal biomarkers of reduced ASV efficacy were noted as follows: (1) an arousal index which markedly exceeded the respiratory event index during positive pressure titration; (2) persistent pressure cycling during long-term ASV therapy, visible in online review systems or reviewing data using freeware; (3) the ASV-associated pressure cycling induced arousals, sleep fragmentation, and blood pressure surges; and (4) elevated ratios of 95th percentile to median tidal volume, minute ventilation, and respiratory rate were associated with pressure cycling. High intraclass coefficients (>0.8) for machine apnea-hypopnea index and other extractable metrics were consistent with stability of patterns over multiple nights of use. Global clinical outcomes correlated negatively with pressure cycling. Conclusions: Potential polysomnographic- and device-related signal biomarkers of ASV efficacy are described and may allow improved estimation of therapeutic effectiveness of adaptive ventilation.

Clinical consequences and economic costs of untreated obstructive sleep apnea syndrome.

OBJECTIVE: To provide an overview of the healthcare and societal consequences and costs of untreated obstructive sleep apnea syndrome. DATA SOURCES: PubMed database for English-language studies with no start date restrictions and with an end date of September 2014. METHODS: A comprehensive literature review was performed to identify all studies that discussed the physiologic, clinical and societal consequences of obstructive sleep apnea syndrome as well as the costs associated with these consequences. There were 106 studies that formed the basis of this analysis. CONCLUSIONS: Undiagnosed and untreated obstructive sleep apnea syndrome can lead to abnormal physiology that can have serious implications including increased cardiovascular disease, stroke, metabolic disease, excessive daytime sleepiness, work-place errors, traffic accidents and death. These consequences result in significant economic burden. Both, the health and societal consequences and their costs can be decreased with identification and treatment of sleep apnea. IMPLICATIONS FOR PRACTICE: Treatment of obstructive sleep apnea syndrome, despite its consequences, is limited by lack of diagnosis, poor patient acceptance, lack of access to effective therapies, and lack of a variety of effective therapies. Newer modes of therapy that are effective, cost efficient and more accepted by patients need to be developed.