Central Sleep Apnea in Patients With Coronary Heart Disease Taking P2Y12 Inhibitors.

ABSTRACT: Central sleep apnea (CSA) is common in patients with heart failure. Recent studies link ticagrelor use with CSA. We aimed to evaluate CSA prevalence in patients with coronary heart disease (CHD) and whether ticagrelor use is associated with CSA. We reviewed consecutive patients with CHD who underwent a polysomnography (PSG) test over a 5-year period from 3 sleep centers. We sampled patients who were on ticagrelor or clopidogrel during a PSG test at a 1:4 ticagrelor:clopidogrel ratio. Patients with an active opioid prescription during PSG test were excluded. Age, left ventricle (LV) dysfunction, and P2Y12 inhibitor use were included in a multivariate logistic regression. A total of 135 patients were included with 26 on ticagrelor and 109 on clopidogrel (age 64.1 ± 11.4, 32% male). High CSA burden (12%) and strict CSA (4.4%) were more common in patients on ticagrelor than in those on clopidogrel (27% vs. 8.3% and 10.0% vs. 1.8%). Ticagrelor use (vs. clopidogrel) was associated with high CSA burden (OR 3.53, 95% CI 1.04-12.9, P = 0.039) and trended toward significance for strict CSA (OR 6.32, 95% CI 1.03-51.4, P = 0.052) when adjusting for age and LV dysfunction. In an additional analysis also adjusting for history of atrial fibrillation, ticagrelor use and strict CSA became significantly associated (OR 10.0, 95% CI 1.32-117, P = 0.035). CSA was uncommon in patients with CHD undergoing sleep studies. Ticagrelor use (vs. clopidogrel) was associated with high CSA burden and trended toward significance for strict CSA.

Obstructive sleep apnea as an independent predictor of postoperative delirium and pain: protocol for an observational study of a surgical cohort.

Introduction: Postoperative delirium and pain are common complications in adults, and are difficult both to prevent and treat. Obstructive sleep apnea (OSA) is prevalent in surgical patients, and has been suggested to be a risk factor for postoperative delirium and pain. OSA also might impact pain perception, and alter pain medication requirements. This protocol describes an observational study, with the primary aim of testing whether OSA is an independent predictor of postoperative complications, focusing on (i) postoperative incident delirium and (ii) acute postoperative pain severity. We secondarily hypothesize that compliance with prescribed treatment for OSA (typically continuous positive airway pressure or CPAP) might decrease the risk of delirium and the severity of pain. Methods and analysis: We will include data from patients who have been enrolled into three prospective studies: ENGAGES, PODCAST, and SATISFY-SOS. All participants underwent general anesthesia for a non-neurosurgical inpatient operation, and had a postoperative hospital stay of at least one day at Barnes Jewish Hospital in St. Louis, Missouri, from February 2013 to December 2017.  Patients included in this study have been assessed for postoperative delirium and pain severity as part of the parent studies. In the current study, determination of delirium diagnosis will be based on the 3-minute Diagnostic Confusion Assessment Method, and the Visual Analogue Pain Scale will be used for pain severity. Data on OSA diagnosis, OSA risk and compliance with treatment will be obtained from the preoperative assessment record. Other variables that are candidate risk factors for delirium and pain will also be extracted from this record. We will use logistic regression to test whether OSA independently predicts postoperative delirium and linear regression to assess OSAs relationship to acute pain severity. We will conduct secondary analyses with subgroups to explore whether these relationships are modified by compliance with OSA treatment.

Phone-Based Interventions in Adolescent Psychiatry: A Perspective and Proof of Concept Pilot Study With a Focus on Depression and Autism.

BACKGROUND: Telemedicine has emerged as an innovative platform to diagnose and treat psychiatric disorders in a cost-effective fashion. Previous studies have laid the functional framework for monitoring and treating child psychiatric disorders electronically using videoconferencing, mobile phones (smartphones), and Web-based apps. However, phone call and text message (short message service, SMS) interventions in adolescent psychiatry are less studied than other electronic platforms. Further investigations on the development of these interventions are needed. OBJECTIVE: The aim of this paper was to explore the utility of text message interventions in adolescent psychiatry and describe a user feedback-driven iterative design process for text message systems. METHODS: We developed automated text message interventions using a platform for both depression (EpxDepression) and autism spectrum disorder (ASD; EpxAutism) and conducted 2 pilot studies for each intervention (N=3 and N=6, respectively). The interventions were prescribed by and accessible to the patients' healthcare providers. EpxDepression and EpxAutism utilized an automated system to triage patients into 1 of 3 risk categories based on their text responses and alerted providers directly via phone and an online interface when patients met provider-specified risk criteria. Rapid text-based feedback from participants and interviews with providers allowed for quick iterative cycles to improve interventions. RESULTS: Patients using EpxDepression had high weekly response rates (100% over 2 to 4 months), but exhibited message fatigue with daily prompts with mean (SD) overall response rates of 66.3% (21.6%) and 64.7% (8.2%) for mood and sleep questionnaires, respectively. In contrast, parents using EpxAutism displayed both high weekly and overall response rates (100% and 85%, respectively, over 1 to 4 months) that did not decay significantly with time. Monthly participant feedback surveys for EpxDepression (7 surveys) and EpxAutism (18 surveys) preliminarily indicated that for both interventions, daily messages constituted the "perfect amount" of contact and that EpxAutism, but not EpxDepression, improved patient communication with providers. Notably, EpxDepression detected thoughts of self-harm in patients before their case managers or caregivers were aware of such ideation. CONCLUSIONS: Text-message interventions in adolescent psychiatry can provide a cost-effective and engaging method to track symptoms, behavior, and ideation over time. Following the collection of pilot data and feedback from providers and patients, larger studies are already underway to validate the clinical utility of EpxDepression and EpxAutism. TRIAL REGISTRATION: Clinicaltrials.gov NCT03002311; https://clinicaltrials.gov/ct2/show/NCT03002311 (Archived by WebCite at http://www.webcitation.org/6qQtlCIS0).

Polyphenols from green tea prevent antineuritogenic action of Nogo-A via 67-kDa laminin receptor and hydrogen peroxide.

Axonal regeneration after injury to the CNS is hampered by myelin-derived inhibitors, such as Nogo-A. Natural products, such as green tea, which are neuroprotective and safe for long-term therapy, would complement ongoing various pharmacological approaches. In this study, using nerve growth factor-differentiated neuronal-like Neuroscreen-1 cells, we show that extremely low concentrations of unfractionated green tea polyphenol mixture (GTPP) and its active ingredient, epigallocatechin-3-gallate (EGCG), prevent both the neurite outgrowth-inhibiting activity and growth cone-collapsing activity of Nogo-66 (C-terminal domain of Nogo-A). Furthermore, a synergistic interaction was observed among GTPP constituents. This preventive effect was dependent on 67-kDa laminin receptor (67LR) to which EGCG binds with high affinity. The antioxidants N-acetylcysteine and cell-permeable catalase abolished this preventive effect of GTPP and EGCG, suggesting the involvement of sublethal levels of H2 O2 in this process. Accordingly, exogenous sublethal concentrations of H2 O2 , added as a bolus dose (5 µM) or more effectively through a steady-state generation (1-2 µM), mimicked GTPP in counteracting the action of Nogo-66. Exogenous H2 O2 mediated this action by bypassing the requirement of 67LR. Taken together, these results show for the first time that GTPP and EGCG, acting through 67LR and elevating intracellular sublethal levels of H2 O2 , inhibit the antineuritogenic action of Nogo-A. Currently, several agents are being evaluated for overcoming axonal growth inhibitors to promote functional recovery after stroke and spinal cord injury. Epigallocatechin-3-gallate (EGCG), present in green tea polyphenol mixture (GTPP), prevents antineuritogenic activity of Nogo-A, a myelin-derived axonal growth inhibitor. The preventive action of EGCG involves the cell-surface-associated 67-kDa laminin receptor and H2 O2 . GTPP may complement ongoing efforts to treat neuronal injuries.>