Kolla, Bhanuprakash

Abstract Introduction Studies that have resulted in recent approval of hypnotics for chronic insomnia disorder (CID) have extremely restrictive inclusion criteria. We sought to determine how many patients seen in a sleep medicine clinic would be eligible to participate in these trials in order to assess the generalizability of these findings to clinical populations. Methods Six-hundred and twenty-eight patients were screened to identify 100 patients who were ≥18 years old, had a diagnosis of CID, and were prescribed a hypnotic medication at a sleep medicine clinic in a quaternary level healthcare center. Information regarding age, sex, body mass index, comorbid diagnoses, sleep schedule, medications, alcohol/tobacco/illicit drug use, caffeine intake, as well as Epworth Sleepiness Scale, Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, and Insomnia Severity Index scores were abstracted. These data were compared against the inclusion and exclusion criteria for recent regulatory Phase III trials of orexin receptor antagonists (suvorexant, lemborexant, daridorexant). Results Of the 100 patients with CID (mean age=56.2 years; 57% female), only 3 patients met eligibility criteria for inclusion. A majority of patients (80%) would have been excluded due to a prior/concurrent trial of cognitive behavioral therapy for insomnia. If this criterion was set aside, only 11 patients would have been eligible to participate. The remaining top reasons for potential exclusion from the regulatory trials were: presence of medical comorbidities (36%), daytime napping (33%), and sleep apnea (30%). Conclusion A very small number of patients with CID seen in a clinical setting met eligibility criteria for clinical trials of hypnotic medications resulting in regulatory approval. This substantially limits the generalizability of findings from these trials and restricts our ability to determine the efficacy of these drugs in clinical populations. Future trials should enroll patients with less restrictive criteria to help determine the effectiveness of these medications in real world settings. Support (if any)

AbstractAimsBrain-derived neurotrophic factor (BDNF) levels may be associated with alcohol use disorders (AUD) and alcohol consumption, correlate with sleep disturbance and be influenced by sex differences and sex hormones. These associations have not been examined in a single sample accounting for all these factors.MethodsData from 190 participants (29.4% female) with AUD were utilized. Sleep quality, craving intensity, depression, anxiety and alcohol consumption were assessed using the Pittsburgh Sleep Quality Index (PSQI), Penn Alcohol Craving Scale (PACS), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7) and Timeline Follow Back for 90 days(TLFB 90). Inventory of Drug Taking Situations (IDTS) assessed the tendency to drink in positive/negative emotional states. Serum BDNF (sBDNF) and plasma sex hormones (estrogen, progesterone, testosterone, FSH and SHBG) were measured. Pearson correlation analyses were used to examine the association between sBDNF and these measures in the entire sample and in men and women separately. Higher order interaction effects between these factors were evaluated for their association with sBDNF using a backward selection model.ResultsNo significant correlations between sBDNF levels and sex hormones, PSQI, PHQ-9, PACS, IDTS scores and alcohol consumption were found (all P-values > 0.05). sBDNF levels were negatively correlated with GAD-7 scores in men (r = −0.1841; P = 0.03). When considering all quadratic and two-way interactions among PSQI, PHQ-9, GAD-7, mean and max drinks/day, number of drinking days, heavy drinking days, and sex no higher order moderating effects of sBDNF levels were found.ConclusionOur study revealed no significant associations between sBDNF and alcohol measures, sleep, depression and sex hormones suggesting limited utility as a biomarker.

AbstractBackground and ObjectivesPatients increasingly rely on the Internet for healthcare information. This study aimed to evaluate the quality of videos on 3,4‐methylenedioxymethamphetamine (MDMA)‐assisted psychotherapy for posttraumatic stress disorder (PTSD) on YouTube™.MethodsYouTube™ was searched for the terms “MDMA” and “PTSD.” The 100 most viewed videos were analyzed using three standard quality measures: Global Quality Scores (GQS), JAMA benchmark, and DISCERN. Viewer engagement features and source of upload, video duration, inclusion of patient narrative and/or MD/DO/PhD, the mention of lack of Food and Drug Administration (FDA) approval, side effects, potential for abuse, and use in conjunction with psychotherapy were recorded.ResultsThe videos were of poor quality (mean GQS: 2.26 ± 0.94/5, JAMA: 1.96 ± 0.45/4, and DISCERN: 29.5 ± 8.2/80). A significant positive association was found between video quality and duration (GQS: r = .5857, p < .0001, JAMA: r = .279, p = .0409, DISCERN: r = .5783, p < .0001). Videos including an MD/DO/PhD had the highest scores (GQS: 2.87/5 [1.22], p = .006, DISCERN: 38.35/80 [13.32], p < .0003). A minority of videos were uploaded by academic institutions (1%); most were from professional organizations (29%). No correlation was found between quality and viewer engagement features‐number of views, subscribers, likes/dislikes, or comments. A majority mentioned that MDMA must be used in conjunction with psychotherapy (85%) and is not FDA‐approved (82%) for PTSD. Only 32% of videos mentioned risks or potential for abuse.ConclusionsThese findings highlight the need for better quality of online health material and an opportunity for involvement of healthcare professionals in the dissemination of accurate health information via content creation.Scientific SignificanceThis is the first study to examine publicly available information on the use of MDMA for PTSD.

Introduction Cognitive behavioural therapy for insomnia (CBT-I) is effective at treating chronic insomnia, yet in-person CBT-I can often be challenging to access. Prior studies have used technology to bridge barriers but have been unable to extensively assess the impact of the digital therapeutic on real-world patient experience and multidimensional outcomes. Among patients with insomnia, our aim is to determine the impact of a prescription digital therapeutic (PDT) (PEAR-003b, FDA-authorised as Somryst; herein called PDT) that provides mobile-delivered CBT-I on patient-reported outcomes (PROs) and healthcare utilisation. Methods and analysis We are conducting a pragmatically designed, prospective, multicentre randomised controlled trial that leverages Hugo, a unique patient-centred health data-aggregating platform for data collection and patient follow-up from Hugo Health. A total of 100 participants with insomnia from two health centres will be enrolled onto the Hugo Health platform, provided with a linked Fitbit (Inspire 2) to track activity and then randomised 1:1 to receive (or not) the PDT for mobile-delivered CBT-I (Somryst). The primary outcome is a change in the insomnia severity index score from baseline to 9-week postrandomisation. Secondary outcomes include healthcare utilisation, health utility scores and clinical outcomes; change in sleep outcomes as measured with sleep diaries and a change in individual PROs including depressive symptoms, daytime sleepiness, health status, stress and anxiety. For those allocated to the PDT, we will also assess engagement with the PDT. Ethics and dissemination The Institutional Review Boards at Yale University and the Mayo Clinic have approved the trial protocol. This trial will provide important data to patients, clinicians and policymakers about the impact of the PDT device delivering CBT-I on PROs, clinical outcomes and healthcare utilisation. Findings will be disseminated to participants, presented at professional meetings and published in peer-reviewed journals. Trial registration number NCT04909229 .

Abstract Introduction Cognitive behavior therapy for insomnia (CBT-I), a first-line therapy for patients with chronic insomnia disorder (ChID), is underutilized due to reduced access to trained providers and other barriers. We developed an interactive care plan (ICP) combining individual aspects of CBT-I. This ICP, which integrates with the electronic health record (EHR), is designed to deliver personalized and scalable CBT-I to patients with ChID. We report data from initial implementation and evaluation of a ChID ICP deployed at a tertiary sleep medicine clinic. Methods The ICP was developed following patient and provider interviews and focus groups. Patients diagnosed with ChID were offered enrollment and engaged in the ICP through an app. The ICP has embedded logic that may escalate care or offer an exit from the program, depending upon the patient’s response to questions. Key variables ascertained from the patient included sleep efficiency (SE), sleep timing and the Insomnia Severity Index (ISI), and how satisfied they were with their progress (Likert scale). We also measured In Basket messaging related to use of the ICP. Results A total of 222 patients [57% female, age=56.4±15.9 years (average ±SD), 92.7% white] were enrolled in the initial 120 days of ICP implementation. Most referrals were initiated by physicians or advanced practitioners (77.9%). ISI at initiation was 15±5.18 and SE was 74.55±16.65%. Patients spent 35.9±26.25 days engaging with the ICP. The ISI score at 28 days was 12.89±4.98 and SE was 78.9±13.4% with both showing significant improvement from baseline (p=0.013; p=0.002; respectively). Self-rated satisfaction with progress did not significantly correlate with actual improvement in ISI or SE (p&gt;0.05). The ICP generated 3.89±2.3 In Basket messages per patient. Conclusion Patients who actively engaged with the ICP showed significant improvements in insomnia severity and sleep efficiency. While a majority of the patients were neutral towards the ICP and only a small minority expressed dissatisfaction, these data indicate that the ICP will have clinical utility in busy sleep medicine practices with reduced access to behavioral sleep specialists. Support (If Any)

Abstract Study Objectives Post-traumatic stress disorder (PTSD) and rapid eye movement (REM) sleep behavior disorder (RBD) share some common features including prominent nightmares and sleep disturbances. We aimed to comparatively analyze REM sleep without atonia (RSWA) between patients with chronic PTSD with and without dream enactment behavior (DEB), isolated RBD (iRBD), and controls. Methods In this retrospective study, we comparatively analyzed 18 PTSD with DEB (PTSD+DEB), 18 PTSD without DEB, 15 iRBD, and 51 controls matched for age and sex. We reviewed medical records to determine PTSD clinical features and quantitatively analyzed RSWA. We used nonparametric analyses to compare clinical and polysomnographic features. Results PTSD patients, both with and without DEB, had significantly higher RSWA than controls (all p &lt; .025, excepting submentalis phasic duration in PTSD+DEB). Most RSWA measures were also higher in PTSD+DEB than in PTSD without DEB patients (all p &lt; .025). Conclusions PTSD patients have higher RSWA than controls, whether DEB is present or not, indicating that REM sleep atonia control is abnormal in chronic PTSD. Further prospective studies are needed to determine whether neurodegenerative risk and disease markers similar to RBD might occur in PTSD patients.

IntroductionUnderstanding the course and determinants of sleep disturbances in alcoholic patients may help identify patients at high risk of persistent sleep problems, relapse and guide treatment interventions.MethodsWe prospectively administered the Pittsburgh Sleep Quality Index (PSQI) to all patients (N = 196) admitted to a 1‐month residential treatment program. Our analysis excluded patients with active drug abuse/dependence. Demographic data, psychiatric diagnoses, Patient Health Questionnaire‐9 (PHQ‐9), Alcohol Use Disorders Identification Test (AUDIT) and Inventory of Drug Taking Situations (IDTS) scores were obtained. Univariate and logistic regression analyses were performed using sex, age, hazardous alcohol use, PHQ‐9 scores, hypnotic use, and use of alcohol as a hypnotic as correlates to admission PSQI scores and improvement in PSQI scores.ResultsA total of 119 alcoholic patients met inclusion criteria (mean age 50.6 ± 13.2 years). The rates of sleep disturbances at admission and discharge were 69.3% and 49.1%, respectively. Self report of using alcohol to fall asleep and use of hypnotics were associated with elevated PSQI scores. Total PSQI scores improved over 4 weeks (p < .001). Change in PSQI scores was not effected by gender, use of hypnotics, hazardous alcohol use, use of alcohol as a hypnotic or co‐morbid psychiatric diagnosis. Older age predicted improvement in PSQI scores in patients with sleep disturbances (p = .004).ConclusionWhile a large proportion of alcoholics had sleep disturbances upon admission and at discharge from a residential treatment program, only older age was associated with improvements in sleep disturbances during early alcohol recovery. (Am J Addict 2014;23:21–26)