Transcranial Magnetic Stimulation of the Default Mode Network to Improve Sleep in Individuals With Insomnia Symptoms: Protocol for a Double-Blind Randomized Controlled Trial.

BACKGROUND: Cortical hyperarousal and ruminative thinking are common aspects of insomnia that have been linked with greater connectivity in the default mode network (DMN). Therefore, disrupting network activity within the DMN may reduce cortical and cognitive hyperarousal and facilitate better sleep. OBJECTIVE: This trial aims to establish a novel, noninvasive method for treating insomnia through disruption of the DMN with repetitive transcranial magnetic stimulation, specifically with continuous theta burst stimulation (cTBS). This double-blind, pilot randomized controlled trial will assess the efficacy of repetitive transcranial magnetic stimulation as a novel, nonpharmacological approach to improve sleep through disruption of the DMN prior to sleep onset for individuals with insomnia. Primary outcome measures will include assessing changes in DMN functional connectivity before and after stimulation. METHODS: A total of 20 participants between the ages of 18 to 50 years with reported sleep disturbances will be recruited as a part of the study. Participants will then conduct an in-person screening and follow-on enrollment visit. Eligible participants then conduct at-home actigraphic collection until their first in-residence overnight study visit. In a double-blind, counterbalanced, crossover study design, participants will receive a 40-second stimulation to the left inferior parietal lobule of the DMN during 2 separate overnight in-residence visits. Participants are randomized to the order in which they receive the active stimulation and sham stimulation. Study participants will undergo a prestimulation functional magnetic resonance imaging scan and a poststimulation functional magnetic resonance imaging scan prior to sleep for each overnight study visit. Sleep outcomes will be measured using clinical polysomnography. After their first in-residence study visit, participants conduct another at-home actigraphic collection before returning for their second in-residence overnight study visit. RESULTS: Our study was funded in September 2020 by the Department of Defense (W81XWH2010173). We completed the enrollment of our target study population in the October 2022 and are currently working on neuroimaging processing and analysis. We aim to publish the results of our study by 2024. Primary neuroimaging outcome measures will be tested using independent components analysis, seed-to-voxel analyses, and region of interest to region of interest analyses. A repeated measures analysis of covariance (ANCOVA) will be used to assess the effects of active and sham stimulation on sleep variables. Additionally, we will correlate changes in functional connectivity to polysomnography-graded sleep. CONCLUSIONS: The presently proposed cTBS protocol is aimed at establishing the initial research outcomes of the effects of a single burst of cTBS on disrupting the network connectivity of the DMN to improve sleep. If effective, future work could determine the most effective stimulation sites and administration schedules to optimize this potential intervention for sleep problems. TRIAL REGISTRATION: ClinicalTrials.gov NCT04953559; https://clinicaltrials.gov/ct2/show/NCT04953559. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51212.

Genetic QT Score and Sleep Apnea as Predictors of Sudden Cardiac Death in the UK Biobank.

Introduction: The goal of this study was to evaluate the association between a polygenic risk score (PRS) for QT prolongation (QTc-PRS), QTc intervals and mortality in patients enrolled in the UK Biobank with and without sleep apnea. Methods: The QTc-PRS was calculated using allele copy number and previously reported effect estimates for each single nuclear polymorphism SNP. Competing-risk regression models adjusting for age, sex, BMI, QT prolonging medication, race, and comorbid cardiovascular conditions were used for sudden cardiac death (SCD) analyses. Results: 500,584 participants were evaluated (56.5 ±8 years, 54% women, 1.4% diagnosed with sleep apnea). A higher QTc-PRS was independently associated with the increased QTc interval duration (p<0.0001). The mean QTc for the top QTc-PRS quintile was 15 msec longer than the bottom quintile (p<0.001). Sleep apnea was found to be an effect modifier in the relationship between QTc-PRS and SCD. The adjusted HR per 5-unit change in QTc-PRS for SCD was 1.64 (95% CI 1.16 - 2.31, p=0.005) among those with sleep apnea and 1.04 (95% CI 0.95 - 1.14, p=0.44) among those without sleep apnea (p for interaction =0.01). Black participants with sleep apnea had significantly elevated adjusted risk of SCD compared to White participants (HR=9.6, 95% CI 1.24 - 74, p=0.03). Conclusion: In the UK Biobank population, the QTc-PRS was associated with SCD among participants with sleep apnea but not among those without sleep apnea, indicating that sleep apnea is a significant modifier of the genetic risk. Black participants with sleep apnea had a particularly high risk of SCD.

Functional connectivity of the default mode network predicts subsequent polysomnographically measured sleep in people with symptoms of insomnia.

Insomnia is often accompanied by excessive pre-sleep rumination. Such ruminative thinking is also associated with increased connectivity of the default mode network (DMN). It is likely that DMN connectivity and associated rumination contribute to the pathogenesis of insomnia. We hypothesized that resting state functional connectivity (rsFC) between the DMN and other brain regions prior to bedtime would predict objectively measured sleep among individuals with insomnia. Twenty participants (12 female; M age = 26.9, SD = 6.6 years) with symptoms of insomnia underwent an rsFC scan in the early evening followed by a night of polysomographically (PSG) measured sleep. Connectivity of the DMN with other brain regions was regressed against several PSG sleep metrics, including time in wake, N1, N2, N3, REM, total sleep time (TST), and sleep efficiency (SE) at a cluster corrected false discovery rate (FDR) correction P < 0.05. The connectivity between DMN and cortical regions was negatively correlated with PSG indices of poorer sleep including time in wake (right angular gyrus) and N1 (precuneus) but positively correlated with time in REM (orbitofrontal cortex), TST (insula, orbitofrontal cortex, superior frontal gyrus, paracingulate gyrus), SE (orbitofrontal cortex). Connectivity between DMN and the pons was negatively correlated with SE. Among individuals with symptoms of insomnia, better sleep was predicted by rsFC between the DMN and cortical regions involved in executive functioning, consciousness, and complex cognition. Findings raise the possibility that future interventions aimed at suppressing pre-sleep DMN activation may weaken synergy between pre-sleep ruminative worry and complex cognitions, potentially ameliorating problems falling asleep.

Comparisons of Sleep, Demographics, and Health-Related Variables in Older Long and Average Duration Sleepers.

Introduction Long sleep duration is associated with many health risks, particularly in older adults, but little is known about other characteristics associated with long sleep duration. Methods Across 5 sites, adults aged 60-80 years who reported sleeping 8-9 h ("long sleepers", n = 95) or 6-7.25 h ("average sleepers", n = 103) were assessed for two weeks using actigraphy and sleep diary. Demographic and clinical characteristics, objective sleep apnea screening, self-reported sleep outcomes, and markers of inflammation and glucose regulation were measured. Results Compared to average sleepers, long sleepers had a greater likelihood of being White and unemployed and/or retired. Long sleepers also reported longer time in bed, total sleep time and wake after sleep onset by sleep diary and by actigraphy. Other measures including medical co-morbidity, apnea/hypopnea index, sleep related outcomes such as sleepiness, fatigue, depressed mood, or markers of inflammation and glucose metabolism did not differ between long and average sleepers. Conclusion Older adults with long sleep duration were more likely to be White, report unemployment and retirement suggesting the social factors or related sleep opportunity contributed to long sleep duration in the sample. Despite known health risks of long sleep duration, neither co-morbidity nor markers of inflammation or metabolism differed in older adults with long sleep duration compared with those with average sleep duration.

A QTc risk score in patients with obstructive sleep apnea.

INTRODUCTION: Patients with obstructive sleep apnea (OSA) are at risk for QTc prolongation, a known risk factor for increased mortality. The pro-QTc score can help identify individuals at increased risk for mortality associated with increased QTc however, it has not been evaluated in patients with OSA. The goal of this study was to evaluate the pro-QTc score in patients with OSA. METHODS: Medical records of patients undergoing a sleep study at our sleep center from February 2012 to August 2020 were analyzed. Presence or absence of OSA was determined by polysomnography. The pro-QTc score was calculated with 1 point assigned for each of the following: female sex, QT-prolonging diagnoses and conditions, QT-prolonging electrolyte abnormalities, and medications with known risk for QT-prolongation. Mortality was determined from the electronic medical record of an integrated healthcare system. RESULTS: There were 2246 patients (age 58 ± 15 years, 54% male, 82 dead) with OSA and 421 patients (age 54 ± 18 years, 43% male, 18 dead) without OSA. Of those with OSA, 1628 (72.5%) had at least one risk factor for QTc prolongation. A higher pro-QTc score was associated with greater mortality in patients with OSA (HR 1.48 per pro-QTc score, p < 0.001, 95% CI 1.3-1.7) but not in patients without OSA (HR 1.25 per pro-QTc score, p = 0.30, 95% CI 0.82-1.9), after adjusting for age, body mass index (BMI), and smoking status. CONCLUSION: In patients with OSA, a higher pro-QTc score was associated with greater mortality.

Circadian acclimatization of performance, sleep, and 6-sulfatoxymelatonin using multiple phase shifting stimuli.

Misalignment between the environment and one's circadian system is a common phenomenon (e.g., jet lag) which can have myriad negative effects on physical and mental health, mental and physiological performance, and sleep. Absent any intervention, the circadian system adjusts only 0.5-1.0 h per day to a shifted light-dark and sleep-wake schedule. Bright light facilitates circadian adjustment, but in field studies, bright light is only modestly better than no stimulus. Evidence indicates that exercise and melatonin can be combined with bright light to elicit larger shifts but no study has combined all of these stimuli or administered them at the times that are known to elicit the largest effects on the circadian system. The aims of this study are to compare the effects of different treatments on circadian adjustment to simulated jet lag in a laboratory. Following 2 weeks of home recording, 36 adults will spend 6.5 consecutive days in the laboratory. Following an 8 h period of baseline sleep recording on the participant's usual sleep schedule on Night 1 (e.g., 0000-0800 h), participants will undergo a 26 h circadian assessment protocol involving 2 h wake intervals in dim light and 1 h of sleep in darkness, repeated throughout the 26 h. During this protocol, all urine voidings will be collected; mood, sleepiness, psychomotor vigilance, and pain sensitivity will be assessed every 3 h, forehead temperature will be assessed every 90 min, and anaerobic performance (Wingate test) will be tested every 6 h. Following, the circadian assessment protocol, the participant's sleep-wake and light dark schedule will be delayed by 8 h compared with baseline (e.g., 0800-1400 h), analogous to travelling 8 times zones westward. This shifted schedule will be maintained for 3 days. During the 3 days on the delayed schedule, participants will be randomized to one of 3 treatments: (1) Dim Red Light + Placebo Capsules, (2) Bright Light Alone, (3) Bright Light + Exercise + Melatonin. During the final 26 h, all conditions and measures of the baseline circadian protocol will be repeated. Acclimatization will be defined by shifts in circadian rhythms of aMT6s, psychomotor vigilance, Wingate Anaerobic performance, mood, and sleepiness, and less impairments in these measures during the shifted schedule compared with baseline. We posit that Bright Light Alone and Bright Light + Exercise + Melatonin will elicit greater shifts in circadian rhythms and less impairments in sleep, mood, performance, and sleepiness compared with Dim Red Light + Placebo Capsules. We also posit that Bright Light + Exercise + Melatonin will elicit greater shifts and less impairments than Bright Light Alone.

Obstructive Sleep Apnea as a Risk Factor for COVID-19 Severity-The Gut Microbiome as a Common Player Mediating Systemic Inflammation via Gut Barrier Dysfunction.

The novel corona virus that is now known as (SARS-CoV-2) has killed more than six million people worldwide. The disease presentation varies from mild respiratory symptoms to acute respiratory distress syndrome and ultimately death. Several risk factors have been shown to worsen the severity of COVID-19 outcomes (such as age, hypertension, diabetes mellitus, and obesity). Since many of these risk factors are known to be influenced by obstructive sleep apnea, this raises the possibility that OSA might be an independent risk factor for COVID-19 severity. A shift in the gut microbiota has been proposed to contribute to outcomes in both COVID-19 and OSA. To further evaluate the potential triangular interrelationships between these three elements, we conducted a thorough literature review attempting to elucidate these interactions. From this review, it is concluded that OSA may be a risk factor for worse COVID-19 clinical outcomes, and the shifts in gut microbiota associated with both COVID-19 and OSA may mediate processes leading to bacterial translocation via a defective gut barrier which can then foster systemic inflammation. Thus, targeting biomarkers of intestinal tight junction dysfunction in conjunction with restoring gut dysbiosis may provide novel avenues for both risk detection and adjuvant therapy.

Markers of ventricular repolarization and overall mortality in sleep disordered breathing.

INTRODUCTION: Variability and prolongation of ventricular repolarization - measured by changes in QT interval and QT variability are independently associated with ventricular arrhythmias, sudden death, and mortality but such studies did not examine the role of sleep-disordered breathing. We aimed to determine whether sleep-disordered breathing moderated the association between measures of ventricular repolarization and overall mortality. METHODS: Eight hundred participants were randomly selected from each of the following four groups in the Sleep Heart Health Study: mild, moderate, severe or no sleep disordered breathing (n = 200 each). Overnight electrocardiograms were analyzed for QTc duration and QT variability (standard deviation of QT intervals, normalized QT interval variance and the short-term interval beat-to-beat QT variability). Cox proportional hazards penalized regression modeling was used to identify predictors of mortality. RESULTS: Eight hundred of 5600 participants were randomly selected. The participants (68 ± 10 years; 56.8% male) were followed for an average of 8.2 years during which time 222 (28.4%) died. QTc, SDQT, and QTVN were associated with the presence of SDB (p = 0.002, p = 0.014, and p = 0.024, respectively). After adjusting for covariates, the presence of sleep-disordered breathing did not moderate the association between QTc length, QT variability and mortality (p > 0.05). CONCLUSION: Sleep-disordered breathing was associated with some measures of ventricular repolarization. However, sleep-disordered breathing was not an effect modifier for the relationship between QTc and QT variability and mortality.

The Hypoglossal Nerve Stimulation as a Novel Therapy for Treating Obstructive Sleep Apnea-A Literature Review.

Obstructive sleep apnea (OSA) is a common sleep disorder that affects all age groups and is associated with many co-morbid diseases (especially cardiovascular diseases). Continuous positive airway pressure (CPAP) is the gold standard for treating OSA. However, adherence to PAP therapy has been a major challenge with an estimated adherence between 20% and 80%. Mandibular advancement devices (MAD) are a good alternative option if used in the appropriate patient. MAD are most effective in mild and moderate OSA but not severe OSA. Surgical options are invasive, not appropriate for severe OSA, and associated with pain and long healing time. Hypoglossal nerve stimulation (HGNS), or upper airway stimulation (UAS), is a novel therapy in treating moderate and severe degrees of OSA in patients who cannot tolerate CPAP therapy. We reviewed the MEDLINE (PubMed) database. The search process yielded 303 articles; 31 met the inclusion and exclusion criteria and were included. We concluded that hypoglossal nerve stimulation is a very effective and novel alternative therapy for moderate and severe OSA in patients who cannot tolerate CPAP therapy. Adherence to HGNS is superior to CPAP. However, more developments are needed to ensure the highest safety profile.

Prescription medications for insomnia are associated with suicidal thoughts and behaviors in two nationally representative samples.

STUDY OBJECTIVES: Z-drugs (eszopiclone, zolpidem, and zaleplon) are commonly used for insomnia but are also associated with suicide risk. However, it is unclear if this association is unique to Z-drugs. Therefore, the present study estimated the associations between multiple prescription insomnia medications and suicidal thoughts and behaviors. METHODS: Data were acquired from the National Survey on Drug Use and Health for 2015-2018 and the National Health and Nutrition Examination Survey for 2005-2018. Samples were balanced on sociodemographic and mental health covariates using inverse probability of treatment weighting. Associations of Z-drugs, trazodone, and sedative benzodiazepines (temazepam, triazolam, flurazepam) with suicidal ideation, planning, and attempts were estimated using binomial logistic regression. RESULTS: In the National Survey on Drug Use and Health, Z-drugs were associated with suicidal ideation (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.14-1.54]), suicide planning (OR, 1.44; 95% CI, 1.19-1.75), and suicide attempts (OR, 1.45; 95% CI, 1.13-1.86) after adjusting for age, sex, race/ethnicity, income, depression, illicit substance use, and the 6-item Kessler Psychological Distress Scale and World Health Organization Disability Assessment Schedule II scores. When analyses accounted for the same factors, sedative benzodiazepines were associated with suicide attempts (OR, 1.76; 95% CI, 1.06-2.87) but not suicidal ideation (OR, 1.37; 95% CI, 0.99-1.88) or suicide planning (OR, 1.39; 95% CI, 0.97-2.00). In the National Health and Nutrition Examination Survey, Z-drugs were associated with suicidal ideation (OR, 2.44; 95% CI, 1.41-4.22), as was trazodone (OR, 2.33; 95% CI, 1.45-3.75), after analyses adjusted for age, sex, race/ethnicity, and exposure to various psychotropic medications. CONCLUSIONS: Multiple classes of prescription insomnia medications are associated with suicidal thinking and behaviors, even after analyses adjusted for measures of mental health.

Differences in sleep timing and related effects between African Americans and non-Hispanic Whites.

STUDY OBJECTIVES: Prior studies have shown a morning chronotype for African Americans compared with non-Hispanic Whites, yet self-reported sleep timing is delayed in African Americans compared with Whites. METHODS: We analyzed data from the Multi-Ethnicity Study of Atherosclerosis, a multisite community-based cohort. Self-reported and actigraphic sleep timing, chronotype measured by the modified Horne-Östberg Morningness-Eveningness Questionnaire, and risk of depression measured by the Center for Epidemiologic Studies Depression scale were examined using nonparametric approaches and linear or logistic regression while comparing between African Americans and Whites and evaluating the effects of delayed sleep phase. RESULTS: In 1,401 participants, there was no difference in chronotype between African Americans and Whites. African Americans were 80% more likely to report a delayed sleep phase (defined as bedtime after midnight) on weekdays and 50% more likely on weekends than were Whites. Actigraphic data showed similar results. Actigraphic midsleep time was delayed 38 minutes on weekdays and 24 minutes on weekends in African Americans compared with Whites. Stratified analysis by chronotype showed that African Americans with a morning or intermediate chronotype had a significantly delayed sleep phase compared with Whites, but there was no difference between African Americans and Whites with an evening chronotype. Delayed sleep phase was associated with depression, but this relationship was only significant in White participants. CONCLUSIONS: African Americans had a delayed sleep phase compared with Whites that was more pronounced in individuals with a morning or intermediate chronotype. Consequences of delayed sleep phase may vary by race and ethnicity.

Matrix metalloproteinase-9 as a messenger in the cross talk between obstructive sleep apnea and comorbid systemic hypertension, cardiac remodeling, and ischemic stroke: a literature review.

STUDY OBJECTIVES: OSA is a common sleep disorder. There is a strong link between sleep-related breathing disorders and cardiovascular and cerebrovascular diseases. Matrix metalloproteinase-9 (MMP-9) is a biological marker for extracellular matrix degradation, which plays a significant role in systemic hypertension, myocardial infarction and postmyocardial infarction heart failure, and ischemic stroke. This article reviews MMP-9 as an inflammatory mediator and a potential messenger between OSA and OSA-induced comorbidities. METHODS: We reviewed the MEDLINE database (PubMed) for publications on MMP-9, OSA, and cardiovascular disease, identifying 1,592 studies and including and reviewing 50 articles for this work. RESULTS: There is strong evidence that MMP-9 and tissue inhibitor of metalloproteinase-1 levels are elevated in patients with OSA (mainly MMP-9), systemic hypertension, myocardial infarction, and postmyocardial infarction heart failure. Our study showed variable results that could be related to the sample size or to laboratory methodology. CONCLUSIONS: MMP-9 and its endogenous inhibitor, tissue inhibitor of metalloproteinase-1, are a common denominator in OSA, systemic hypertension, myocardial infarction, and heart failure. This characterization makes MMP-9 a target for developing novel selective inhibitors that can serve as adjuvant therapy in patients with OSA, which may ameliorate the cardiovascular and cerebrovascular mortality associated with OSA.

Effect of wearables on sleep in healthy individuals: a randomized crossover trial and validation study.

STUDY OBJECTIVES: The purpose of this study was to determine whether a wearable sleep-tracker improves perceived sleep quality in healthy participants and to test whether wearables reliably measure sleep quantity and quality compared with polysomnography. METHODS: This study included a single-center randomized crossover trial of community-based participants without medical conditions or sleep disorders. A wearable device (WHOOP, Inc.) was used that provided feedback regarding sleep information to the participant for 1 week and maintained sleep logs versus 1 week of maintained sleep logs alone. Self-reported daily sleep behaviors were documented in sleep logs. Polysomnography was performed on 1 night when wearing the wearable. The Patient-Reported Outcomes Measurement Information System sleep disturbance sleep scale was measured at baseline, day 7 and day 14 of study participation. RESULTS: In 32 participants (21 women; 23.8 ± 5 years), wearables improved nighttime sleep quality (Patient-Reported Outcomes Measurement Information System sleep disturbance: B = -1.69; 95% confidence interval, -3.11 to -0.27; P = .021) after adjusting for age, sex, baseline, and order effect. There was a small increase in self-reported daytime naps when wearing the device (B = 3.2; SE, 1.4; P = .023), but total daily sleep remained unchanged (P = .43). The wearable had low bias (13.8 minutes) and precision (17.8 minutes) errors for measuring sleep duration and measured dream sleep and slow wave sleep accurately (intraclass coefficient, 0.74 ± 0.28 and 0.85 ± 0.15, respectively). Bias and precision error for heart rate (bias, -0.17%; precision, 1.5%) and respiratory rate (bias, 1.8%; precision, 6.7%) were very low compared with that measured by electrocardiogram and inductance plethysmography during polysomnography. CONCLUSIONS: In healthy people, wearables can improve sleep quality and accurately measure sleep and cardiorespiratory variables. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Assessment of Sleep by WHOOP in Ambulatory Subjects; Identifier: NCT03692195.

Socioeconomic Inequities in Adherence to Positive Airway Pressure Therapy in Population-Level Analysis.

(a) Background: In patients with sleep apnea, poor adherence to positive airway pressure (PAP) therapy has been associated with mortality. Regional studies have suggested that lower socioeconomic status is associated with worse PAP adherence but population-level data is lacking. (b) Methods: De-identified data from a nationally representative database of PAP devices was geo-linked to sociodemographic information. (c) Results: In 170,641 patients, those in the lowest quartile of median household income had lower PAP adherence (4.1 + 2.6 hrs/night; 39.6% adherent by Medicare criteria) than those in neighborhoods with highest quartile median household income (4.5 + 2.5 hrs/night; 47% adherent by Medicare criteria; p < 0.0001). In multivariate regression, individuals in neighborhoods with the highest income quartile were more adherent to PAP therapy than those in the lowest income quartile after adjusting for various confounders (adjusted Odds Ratio (adjOR) 1.18; 95% confidence interval (CI) 1.14, 1.21; p < 0.0001). Over the past decade, PAP adherence improved over time (adjOR 1.96; 95%CI 1.94, 2.01), but health inequities in PAP adherence remained even after the Affordable Care Act was passed. (d) Conclusion: In a nationally representative population, disparities in PAP adherence persist despite Medicaid expansion. Interventions aimed at promoting health equity in sleep apnea need to be undertaken.

QT prolongation and sudden cardiac death risk in hypertrophic cardiomyopathy.

INTRODUCTION: Risk assessment for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) remains complex. The goal of this study was to assess electrocardiogram (ECG)-derived risk factors on SCD in a large HCM population Methods: Retrospective review of adults with HCM evaluated at Mayo Clinic, Rochester, MN from 1 December 2002 to 31 December 2012 was performed. Data inclusive of ECG and 24-hour ambulatory Holter monitor were assessed. SCD events were documented by ventricular fibrillation (VF) noted on implantable cardioverter defibrillator (ICD), or appropriate VT or VF-terminating ICD shock. RESULTS: Overall, 1615 patients (mean age 53.7 ± 15.2 years; 943 males, 58.4%) were assessed, with mean follow-up 2.46 years and 110 SCD events. Via logistic regression (n = 820), the odds of SCD increased with increasing number of conventional risk factors. With one risk factor the OR was 4.88 (p < .0001; CI 2.22-10.74), two risk factors the OR was 6.922 (p < .0001; CI 2.94-16.28) and three or more risk factors, the OR was 13.997 (p < .0001; CI 5.649-34.68). Adding QTc > 450 to this logistic regression model had OR 1.722 (p = .04, CI 1.01-2.937) to predict SCD. QTc ≥ 450 was a significant predictor for death (HR 1.88, p = .021, CI 1.10-3.20). There was no correlation between sinus bradycardia, sinus tachycardia, first degree AV block, atrial fibrillation, left bundle branch block, right bundle branch block, premature atrial complexes, premature ventricular complexes, supraventricular tachycardia, PR interval, QRS interval and SCD. CONCLUSIONS: Prolonged QTc was a risk factor for SCD and death even when controlling for typical risk factors.

Practical Implementation of a Single-Night Split-Titration Protocol With BPAP-ST and AVAPS in Patients With Neuromuscular Disease.

STUDY OBJECTIVES: At the sleep laboratory, noninvasive positive pressure ventilation titration protocols in patients with neuromuscular disease (NMD) are based on standard pressure cycle devices in a spontaneous/timed mode (BPAP-ST). Experience integrating protocols on average volume-assured pressure support (AVAPS) mode is limited, prompting us to develop a practical single-night titration protocol that provides information to assist clinicians and patients as they decide between BPAP-ST and AVAPS modes. METHODS: We implemented a sequential titration protocol of BPAP-ST followed by AVAPS during a single-night polysomnography study in patients with NMD and reported polysomnographic and clinical metrics. RESULTS: There were 27 patients who completed the protocol: 14 (52%) were male with median and interquartile range (IQR) 64 (59 to 70) years of age and body mass index of 29.6 (25.6-32) kg/m2. They had median (IQR) maximal percent predicted inspiratory and expiratory pressures, and percent vital capacity of 33 (24 to 54), 34 (22 to 47) and 60 (47 to 74), respectively. At final titration of each device, average tidal volume and nadir non-rapid eye movement sleep oxyhemoglobin saturation (SpO2) were higher and respiratory rate/tidal volume, transcutaneous CO2, and arousal index were lower on AVAPS (P < .05) in comparison with BPAP-ST. Full face mask was used in 23 patients (85%). None of the other ventilatory or sleep parameters differed significantly between BPAP-ST and AVAPS (P > .05) sessions. CONCLUSIONS: A practical single-night split-titration protocol with BPAP-ST and AVAPS can successfully be implemented in patients with NMD, assisting clinicians and patients with the decision on initial treatment modalities and settings.

Cardiac Troponin T Risk Stratification Model Predicts All-Cause Mortality Following Kidney Transplant.

BACKGROUND: We evaluated the role of increased cardiac troponin T (cTnT), vascular, and cardiac diseases in predicting 5 and 10-year all-cause mortality after kidney transplantation. METHODS: We reviewed a cohort of 764 kidney transplant recipients and analyzed pertinent cardiovascular risk factors at the time of transplant evaluation. Proportional hazards regression analysis with bootstrapping method was utilized to provide a risk stratification score for mortality. RESULTS: Mean age was 58.8 years (SD 12.1) and median follow-up was 7.0 years (range 1 day to 18.0 years). Fifty-four percent of patients (n = 415) had cTnT measured (median 0.02 ng/mL, range 0.01-4.91). Fifty-three percent (n = 407) had vascular disease, 59% (n = 448) had diabetes, and 44% (n = 336) had cardiac disease pre-transplant. Sixty percent (n = 460) required dialysis. Older age, increased cTnT, pre-transplant vascular and cardiac diseases predicted mortality in multivariate analysis. We derived 2 scoring systems with and without cTnT - the ACV and ACTV scores (age, cardiac disease, elevated cTnT, and vascular disease) - as predictors of mortality after kidney transplant. Point assignments were: age 60-69 years (1), age ≥70 years (2), cardiac disease (1), cTnT ≥0.04 ng/mL (1), and vascular disease (1). Both scoring systems significantly predicted mortality. The ACTV score better delineated risk stratification across score levels (0-2, 3-4, and 5 points). CONCLUSIONS: We developed a risk schema predictive of all-cause mortality after kidney transplant in a derivation cohort. The ACTV score, including an elevated cTnT, provided superior prediction compared to a scoring system without cTnT. Further studies to validate these findings are needed.

Public Awareness, Usage, and Predictors for the Use of Doctor Rating Websites: Cross-Sectional Study in England.

BACKGROUND: With the advent and popularity of social media and consumer rating websites, as well as the emergence of the digitally engaged patient, there has been an increased interest in doctor rating websites or online patient feedback websites, both inside and outside academia. However, there is very little known about how the public across England views such rating websites as a mode to give patient experience feedback. OBJECTIVE: The aim of the overall study was to measure and understand public awareness, usage, and attitudes towards doctor rating websites as a mode to give experiential feedback about GPs in general practice in England. This paper reports on the findings of one of the aims of the study, which was to measure public awareness, current usage and future consideration of usage of online patient feedback websites, within the context of other feedback methods, This could allow the value of online patient feedback websites to be determined from the patients' perspective. METHODS: A mixed methods population questionnaire was designed, validated and implemented face-to-face using a cross-sectional design with a representative sample of the public (n=844) in England. The results of the questionnaire were analyzed using chi-square tests, binomial logistic regressions, and content analysis. The qualitative results will be reported elsewhere. RESULTS: Public awareness of online patient feedback websites as a channel to leave experiential feedback about GPs was found to be low at 15.2% (128/844). However, usage and future consideration to use online patient feedback websites were found to be extremely low, with current patient usage at just 0.4% (3/844), and patient intention to use online patient feedback in the future at 17.8% (150/844). Furthermore, only 4.0-5.0% of those who would consider leaving feedback about a GP in the future selected doctor rating websites as their most preferred method; more than half of patients said they would consider leaving feedback about GPs using another method, but not using an online patient feedback website. CONCLUSIONS: The findings suggest that online patient feedback websites may not be an effective channel for collecting feedback on patient experience in general practice. Feedback on online patient feedback websites is not likely to be representative of the patient experience in the near future, challenging the use of online patient feedback not just as a mode for collecting patient experience data, but for patient choice and monitoring too. We recommend the National Health Service channels its investment and resources towards providing more direct and private feedback methods in general practice (such as opportunities for face-to-face feedback, email-based feedback, and web-based private feedback forms), as these are currently much more likely to be used by the majority of patients in England.

A Practical Review of the Emerging Direct Anticoagulants, Laboratory Monitoring, and Reversal Agents.

Millions of patients in the United States use anticoagulation for a variety of indications, such as the prevention of stroke in those with atrial fibrillation (AF) and the treatment and prevention of venous thrombosis. For over six decades warfarin was the only available oral anticoagulant, but now several DOACs are available and their use has become more prevalent in recent years. In spite of this increased use, many physicians remain reluctant to prescribe DOACs due to concerns about bleeding and reversibility.