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Wesley Elon Fleming,1 Jon-Erik C Holty,2 Richard K Bogan,3 Dennis Hwang,4 Aliya S Ferouz-Colborn,4 Rohit Budhiraja,5 Susan Redline,5 Edith Mensah-Osman,6 Nadir Ishag Osman,6 Qing Li,7 Armaghan Azad,1 Susann Podolak,1 Michael K Samoszuk,8 Amabelle B Cruz,8 Yang Bai,8 Jiuliu Lu,8 John S Riley,8 Paula C Southwick8 1Sleep Center Orange County, Irvine, CA, USA; 2Stanford Medical School, VA Palo Alto Health Care System, Pulmonary, Critical Care and Sleep Medicine Section, Palo Alto, CA, USA; 3SleepMed Inc., Bogan Sleep Consultants, LLC, Columbia, SC, USA; 4Sleep Medicine Department, Southern California Permanente Medical Group, Kaiser Permanente, Fontana Medical Center, Fontana, CA, USA; 5Division of Sleep Medicine, Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, USA; 6EENA Comprehensive Neurology and Sleep Center, Boynton Beach, FL, USA; 7South Bend Medical Foundation, New Technology and Test Development, South Bend, IN, USA; 8Clinical Research Department, Beckman Coulter, Inc., Brea, CA, USAPurpose: Obstructive sleep apnea (OSA) is a highly prevalent disorder associated with increased risk for cardiovascular disease, diabetes, and other chronic conditions. Unfortunately, up to 90% of individuals with OSA remain without a diagnosis or therapy. We assess the relationship between OSA and blood biomarkers, and test the hypothesis that combinations of markers provide a characteristic OSA signature with diagnostic screening value. This validation study was conducted in an independent cohort in order to replicate findings from a prior feasibility study.Patients and methods: This multicenter prospective study consecutively enrolled adult male subjects with clinically suspected OSA. All subjects underwent overnight sleep studies. An asymptomatic control group was also obtained. Five biomarkers were tested: glycated hemoglobin (HbA1c), C-reactive protein (CRP), uric acid, erythropoietin (EPO), and interleukin-6 (IL-6).Results: The study enrolled 264 subjects. The combination of HbA1c+CRP+EPO (area under the curve 0.78) was superior to the Epworth Sleepiness Scale (ESS; 0.53) and STOP-Bang (0.70) questionnaires. In non-obese subjects, the combination of biomarkers (0.75) was superior to body mass index (BMI; 0.61). Sensitivity and specificity results, respectively, were: HbA1c+CRP+EPO (81% and 60%), ESS (78% and 19%), STOP-Bang (75% and 52%), BMI (81% and 56%), and BMI in non-obese patients (81% and 38%).Conclusion: We verify our hypothesis and replicate our prior feasibility findings that OSA is associated with a characteristic signature cluster of biomarker changes in men. Concurrent elevations of HbA1c, CRP, and EPO levels should generate a high suspicion of OSA and may have utility as an OSA screening tool. Biomarker combinations correlate with OSA severity and, therefore, may assist sleep centers in identifying and triaging higher risk patients for sleep study diagnosis and treatment.Keywords: obstructive sleep apnea, OSA, screening, diagnosis, biomarkers, CRP, HbA1c, erythropoietin, EPO, uric acid, IL-6

Amoxicillin-loaded microcapsules were prepared by ionotropic gelation of sodium alginate (ALG) with chitosan (CS) in presence of calcium chloride as gastroretentive delivery system. The effect of pH, concentration of ALG, CS and calcium chloride, and drug : ALG ratio were optimized in this study for minimizing the degradation of drug in acidic environment and increasing the loading efficacy and mucoadhesive efficiency of microcapsules. The optimum condition for prepared CS-ALG microcapsules was 2%w/v ALG, 0.75%w/v CS (pH5.0), and 1.0% w/v calcium chloride. The resulting microcapsules had drug entrapment efficiency of 84% and average size of 840 μm. CS concentration significantly influenced particle size and encapsulation efficiency of CS-ALG microcapsules (P<0.05). Decrease in the drug: ALG ratio resulted in an increased release of amoxicillin in acidic media. The relative decomposition of drug after encapsulation in CS-ALG microcapsules was decreased to 20.7%, 41.9%, and 83.3% in 2, 4, and 8 hours, respectively. [ABSTRACT FROM AUTHOR]

Background: Studies examining sleep in the hemodialysis (HD) population have largely lacked an adequate comparison group. It therefore is uncertain whether poor sleep quality in the HD population reflects age, chronic health conditions, or effects of conventional HD therapy.Study Design: Cross-sectional matched-group study.Setting& Participants: Forty-six in-center HD patients were compared with 137 community participants participating in the Sleep Heart Health Study matched for age, sex, body mass index, and race.Predictor: HD patients compared with community-dwelling non-HD participants.Outcomes& Measurements: Home unattended polysomnography was performed and scored by using similar protocols. Sleep habits and sleepiness were assessed by using the Sleep Habits Questionnaire and Epworth Sleepiness Scale.Results: Average age of study samples was 63 years, 72% were white, and average body mass index was 28 +/- 5 kg/m(2). HD patients were significantly more likely than community participants to have short sleep (odds ratio, 3.27; 95% confidence interval, 1.16 to 9.25) and decreased sleep efficiency (odds ratio, 5.5; 95% confidence interval, 1.5 to 19.6). HD patients reported more difficulty getting back to sleep (odds ratio, 2.25; 95% confidence interval, 1.11 to 4.60) and waking up too early (odds ratio, 2.39; 95% confidence interval, 1.01 to 5.66). There was no association between polysomnography sleep time and self-reported sleep time (r = 0.09; P = 0.6) or between the Epworth Sleepiness Scale and severity of sleep apnea (r = 0.10; P = 0.5) in the HD population.Limitations: The study was limited to participants older than 45 years.Conclusions: Kidney failure treated with thrice-weekly HD is significantly associated with poor subjective and objective sleep quality. [ABSTRACT FROM AUTHOR]

Objective: To characterize the association between sleep-disordered breathing (SDB) and impaired fasting glucose (IFG), impaired glucose tolerance (IGT), combined IFG and IGT, and occult diabetes in individuals of different body habitus.Research Design and Methods: Cross-sectional analysis of 2,588 participants (aged 52-96 years; 46% men) without known diabetes. SDB was defined as respiratory disturbance index >or=10 events/h. IFG, IGT, occult diabetes, and body weight were classified according to recent accepted guidelines. Participants with and without SDB were compared on prevalence and odds ratios for measures of impaired glucose metabolism (IGM), adjusting for age, sex, race, BMI, and waist circumference.Results: SDB was observed in 209 nonoverweight and 1,036 overweight/obese participants. SDB groups had significantly higher adjusted prevalence and adjusted odds of IFG, IFG plus IGT, and occult diabetes. The adjusted odds ratio for all subjects was 1.3 (95% CI 1.1-1.6) for IFG, 1.2 (1.0-1.4) for IGT, 1.4 (1.1-2.7) for IFG plus IGT, and 1.7 (1.1-2.7) for occult diabetes.Conclusions: SDB was associated with occult diabetes, IFG, and IFG plus IGT, after adjusting for age, sex, race, BMI, and waist circumference. The magnitude of these associations was similar in nonoverweight and overweight participants. The consistency of associations across all measures of IGM and body habitus groups and the significant association between SDB and IFG plus IGT, a risk factor for rapid progression to diabetes, cardiovascular disease, and mortality, suggests the importance of SDB as a risk factor for clinically important levels of metabolic dysfunction. [ABSTRACT FROM AUTHOR]

Pulmonary involvement is common in patients with portal hypertension and can manifest in diverse manners. Changes in pulmonary arterial resistance, manifesting either as the hepatopulmonary syndrome or portopulmonary hypertension (PPHTN), have been increasingly recognized in these patients in recent years. This review summarizes the clinicopathologic features, diagnostic criteria, as well as the latest concepts in the pathogenesis and management of PPHTN, which is defined as an elevated pulmonary artery pressure in the setting of an increased pulmonary vascular resistance and a normal wedge pressure in a patient with portal hypertension. [ABSTRACT FROM AUTHOR]

In a TDMA standard such as DECT, low bit-rate transmission is feasible either at the cost of efficiency (shorter slots with fixed overhead per slot) or increased latency (longer frames). This paper proposes a new scheme for low bit-rate low-latency channelization in the DECT standard, in which data can be efficiently transmitted at rates as low as 10 kbps. This could be useful for sending acknowledgments for a high-speed data communication link, or for vocoder/VoIP traffic. The proposed scheme enables efficient low bit-rate transmission by dividing a DECT channel into four subbands, and by employing a new slot structure wherein TDMA overhead is kept to a minimum. It is shown that the proposed scheme can coexist with the DECT system and can be implemented using existing IMT-2000 DECT hardware with minor modifications. A comparison is also made of the proposed scheme with existing options for low bit-rate channelization in DECT.

Study Objectives: This analysis determined the association between obstructive sleep apnea (OSA) with hypopneas defined by a 3% O 2 desaturation or arousal (3%A), but not by a hypopnea criterion of ≥ 4% (4%), and subjective sleepiness., Methods: Data were analyzed from Sleep Heart Health Study participants who had polysomnography (N = 6307) regarding OSA and subjective sleepiness scores (Epworth Sleepiness Scale, ESS). The apnea hypopnea index (AHI) was classified based on 3% only, 3%A only, and 4% definitions of hypopneas., Results: Of the 3326 participants without 4% OSA, 67.6% (n = 2247) had 3%A only OSA. The ESS score was higher in 3%A only OSA than in those without OSA (7.44 ± 4.2 vs 7.07 ± 4.3, P = 0.02). Of those without 4% OSA, 40.2% (n = 1336) had 3% only OSA. The ESS score was higher in those with 3% only OSA than those with no OSA (7.72 ± 4.3 vs 7.05 ± 4.2, P < 0.001). A linear regression model demonstrated a trend towards significance for the 3%A only AHI as an independent predictor of ESS when controlled for age, BMI, and sex (P = 0.051). The association of 3% only AHI with the ESS was stronger (P = 0.003). However, 23.3% of the participants with hypersomnia would not qualify as having OSA if arousals were excluded from the definition of OSA., Conclusion: The current study found that the presence and severity of OSA is associated with higher ESS scores in persons with 3%A only OSA. Hence, the use of the 4% hypopnea definition will result in the failure to identify and treat a significant number of individuals with OSA who have subjective sleepiness., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The aim of this retrospective analysis is to determine the most frequently prescribed medications for the treatment of NREM parasomnias and evaluate reported outcomes. We performed a retrospective chart review of all patients with NREM parasomnia diagnosed within Brigham and Women's Hospital (BWH) clinics examining the date of diagnosis, date of starting therapy, comorbidities, type of medication prescribed, and the reported change in symptoms or side effects at follow-up visits. From 2012 to 2019, 110 patients (59 females, 51 male) at BWH clinics received a diagnosis of NREM parasomnia, including sleepwalking and night terrors. The mean age was 44. Comorbidities included obstructive sleep apnea (OSA) (46%), periodic limb movement syndrome (PLMS) (13%), insomnia (19%), Restless leg syndrome (RLS) (9%), epilepsy (4%), and REM behavior disorder (RBD) (9%). Initial treatment strategies include behavioral and safety counseling only (34%), pharmacological treatment (29%), treatment of any comorbidity (28%), and combined treatment of any of the above (9%). Improvement was reported with: treatment of OSA ( n = 23 52% reported improvement), melatonin ( n = 8, improvement reported by 88%.,benzodiazepine ( n = 7, improvement reported by 57%). Treating comorbid conditions is a frequent treatment strategy, often associated with symptom improvement. The pharmacologic treatment most commonly included melatonin and benzodiazepines. Comprehensive management should include behavioral and safety recommendations, assessment of comorbid conditions, and individually tailored pharmaceutical treatment.

Study Objectives: Attended manual continuous positive airway pressure (CPAP) titration is the standard practice for determining optimal positive airway pressures for obstructive sleep apnea (OSA) treatment. However, an unattended single night auto-titrating positive airway pressure (APAP) titration is an alternative. The goal of this study was to determine whether therapeutic CPAP pressures determined during manual titrations are higher than APAP-generated surrogate pressures., Methods: We conducted a retrospective review of 165 adults with uncomplicated OSA who had full/split-night manual CPAP titrations prior to commencing treatment with APAP. Demographic and clinical data including 30-day APAP compliance data were obtained. We compared the recommended CPAP pressure from manual titrations with the 90th/95th percentile pressure generated from APAP usage over 30 days., Results: The recommended CPAP pressures during the manual titrations were higher than the 90th/95th percentile pressures generated from APAP (11.4 ± 3.4 vs 10.3 ± 2.4 cmH2O; P = .000). Almost half the group (41.9%) had their manually derived titration pressure at least 1.5 cm above the 90th/95th percentile pressure. In multivariate analyses, body mass index was the only variable that predicted higher manual titration pressures. Notably, the average residual apnea-hypopnea index on 30-day APAP data was less than the average residual apnea-hypopnea index observed at the recommended pressure during the manual titration (5.0 ± 4.3 vs 7.2 ± 8.5; P = .006)., Conclusions: Manual CPAP titrations may overestimate pressure requirements, particularly in patients with higher body mass index, and may not be necessary in managing patients with uncomplicated OSA. APAP appears to be at least as effective as single-pressure CPAP, while delivering lower positive airway pressure., Citation: Fashanu OS, Budhiraja R, Batool-Anwar S, Quan SF. Titration studies overestimate continuous positive airway pressure requirements in uncomplicated obstructive sleep apnea. J Clin Sleep Med . 2021;17(9):1859-1863., (© 2021 American Academy of Sleep Medicine.)

Significant research in reservoir computing over the past two decades has revived interest in recurrent neural networks. Owing to its ingrained capability of performing high-speed and low-cost computations this has become a panacea for multi-variate complex systems having non-linearity within their relationships. Modelling economic and financial trends has always been a challenging task owing to their volatile nature and no linear dependence on associated influencers. Prior studies aimed at effectively forecasting such financial systems, but, always left a visible room for optimization in terms of cost, speed and modelling complexities. Our work employs a reservoir computing approach complying to echo-state network principles, along with varying strengths of time-delayed feedback to model a complex financial system. The derived model is demonstrated to act robustly towards influence of trends and other fluctuating parameters by effectively forecasting long-term system behavior. Moreover, it also re-generates the financial system unknowns with a high degree of accuracy when only limited future data is available, thereby, becoming a reliable feeder for any long-term decision making or policy formulations., Competing Interests: The authors have declared that no competing interests exist.

Study Objectives: Some prior studies have demonstrated an increase in mortality associated with obstructive sleep apnea (OSA) utilizing a definition of OSA that requires a minimum 4% oxygen desaturation to identify a hypopnea. No large community-based studies have determined the risk of long-term mortality with OSA with hypopneas defined by a ≥3% O 2 desaturation or arousal (AHI3%A)., Methods: Data from 5591 Sleep Heart Health Study participants without prevalent cardiovascular disease at baseline who underwent polysomnography were analyzed regarding OSA diagnosed using the AHI3%A criteria and all-cause mortality over a mean follow up period of 10.9±3.2 years., Results: There were 1050 deaths in this group during the follow-up period. A Kaplan-Meir plot of survival revealed a reduction in survival with increasing AHI severity. Cox proportional hazards regression models revealed significantly increased all-cause mortality risk with increasing AHI, hazard ratio (HR, 95% CI) 1.13 (1.04-1.23), after adjusting for age, sex, race, BMI, cholesterol, HDL, self-reported hypertension and/or diabetes and smoking status. In categorical models, the mortality risk was significantly higher with severe OSA [adjusted HR 1.38 (1.09-1.76)]. When stratified by gender or age, severe OSA was associated with increased risk of death in men [adjusted HR 1.14 (1.01-1.28)] and in those <70 years of age [adjusted HR 1.51 (1.02-2.26)]. In contrast, AHI severity was not associated with increased mortality in women or those ≥70 years of age in fully adjusted models., Conclusion: Severe AHI3%A OSA is associated with significantly increased mortality risk, especially in men and those <70 years of age.

Study Objectives: This analysis determined ∼5-year incident hypertension rates using the 2017 American College of Cardiology/American Heart Association blood pressure (BP) guidelines in individuals with obstructive sleep apnea (OSA) with hypopneas defined by a ≥ 3% oxygen desaturation or arousal but not by a hypopnea criterion of ≥ 4% oxygen desaturation (4% only)., Methods: Data were analyzed from participants in the Sleep Heart Health Study exam 2 (n = 1219) who were normotensive (BP ≤ 120/80 mm Hg) at exam 1. The AHI at exam 1 was classified into 4 categories of OSA severity: < 5, 5 ≤ 15, 15 ≤ 30, and ≥ 30 events/h using both the 3% oxygen desaturation or arousal and the 4% only definitions. Three definitions of hypertension-elevated BP (> 120/80 mm Hg), stage 1 (> 130/80 mm Hg), and stage 2 (> 140/90 mm Hg)-were used to determine incidence rates at exam 2., Results: Five-year follow-up was available for 476 participants classified as having OSA by the 3% oxygen desaturation or arousal criterion but not by the 4% only standard at exam 1. Incident hypertension using American College of Cardiology/American Heart Association-defined BP categories in these discordantly classified individuals were 15% (elevated BP), 15% (stage 1), and 6% (stage 2). Hypertensive medications were used in 4% of participants who were normotensive. The overall incidence rate of at least an elevated BP was 40% (191/476) in those with OSA defined using the 3% oxygen desaturation or arousal criterion but not by the 4% only criterion., Conclusions: Use of the 4% only hypopnea definition resulted in the failure to identify a significant number of individuals with OSA who eventually developed hypertension and could have benefited from earlier diagnosis and treatment., (© 2020 American Academy of Sleep Medicine.)

Objective: We sought to assess the prevalence, correlates, and consequences of periodic limb movements of sleep (PLMS) in persons with obstructive sleep apnea (OSA) and the effect (worsening or improvement) of continuous positive airway pressure (CPAP) therapy on PLMS in a large prospective multicenter randomized controlled trial., Methods: We performed retrospective analyses of data from the Apnea Positive Pressure Long-term Efficacy Study, a prospective multicenter randomized controlled trial. A total of 1,105 persons with OSA enrolled in this study underwent a polysomnographic investigation at baseline, another one for CPAP titration, and another study 6 months after randomization to either active CPAP or sham CPAP., Results: Of all participants, 19.7% had PLM index (PLMI) ≥10/hour, 14.8% had PLMI ≥15/hour, 12.1% had PLMI ≥20/hour, 9.3% had PLMI ≥25/hour, and 7.5% had PLMI ≥30/hour. The odds of having a PLMI ≥10 were higher in older participants (odds ratio [OR] 1.03, p < 0.001), men (OR 1.63. p = 0.007), those using antidepressants (OR 1.48. p = 0.048), and those with higher caffeine use (OR 1.01, p = 0.04). After controlling for OSA and depression, PLMS were associated with increased sleep latency, reduced sleep efficiency, and reduced total sleep time. No significant relationships were noted between PLMS frequency and subjective sleepiness (Epworth Sleepiness Scale score) or objective sleepiness (Maintenance of Wakefulness Test). There was no differential effect of CPAP in comparison to sham CPAP on PLMS after 6 months of therapy., Conclusions: PLMS are common in patients with OSA and are associated with a significant reduction in sleep quality over and above that conferred by OSA. Treatment with CPAP does not affect the severity of PLMS., (© 2019 American Academy of Neurology.)