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      Proof of Concept Trial of Dronabinol in Obstructive Sleep Apnea

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          Abstract

          Study Objective: Animal data suggest that Δ 9-TetraHydroCannabinol (Δ 9THC) stabilizes autonomic output during sleep, reduces spontaneous sleep-disordered breathing, and blocks serotonin-induced exacerbation of sleep apnea. On this basis, we examined the safety, tolerability, and efficacy of dronabinol (Δ 9THC), an exogenous Cannabinoid type 1 and type 2 (CB1 and CB2) receptor agonist in patients with Obstructive Sleep Apnea (OSA). Design and Setting: Proof of concept; single-center dose-escalation study of dronabinol. Participants: Seventeen adults with a baseline Apnea Hypopnea Index (AHI) ≥15/h. Baseline polysomnography (PSG) was performed after a 7-day washout of Continuous Positive Airway Pressure treatment. Intervention: Dronabinol was administered after baseline PSG, starting at 2.5 mg once daily. The dose was increased weekly, as tolerated, to 5 mg and finally to 10 mg once daily. Measurements and Results: Repeat PSG assessments were performed on nights 7, 14, and 21 of dronabinol treatment. Change in AHI (ΔAHI, mean ± SD) was significant from baseline to night 21 (−14.1 ± 17.5; p = 0.007). No degradation of sleep architecture or serious adverse events was noted. Conclusion: Dronabinol treatment is safe and well-tolerated in OSA patients at doses of 2.5–10 mg daily and significantly reduces AHI in the short-term. These findings should be confirmed in a larger study in order to identify sub-populations with OSA that may benefit from cannabimimetic pharmacologic therapy.

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          Most cited references15

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          Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force.

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            EEG arousals: scoring rules and examples: a preliminary report from the Sleep Disorders Atlas Task Force of the American Sleep Disorders Association.

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              Interprofessional education: effects on professional practice and healthcare outcomes (update).

              The delivery of effective, high-quality patient care is a complex activity. It demands health and social care professionals collaborate in an effective manner. Research continues to suggest that collaboration between these professionals can be problematic. Interprofessional education (IPE) offers a possible way to improve interprofessional collaboration and patient care. To assess the effectiveness of IPE interventions compared to separate, profession-specific education interventions; and to assess the effectiveness of IPE interventions compared to no education intervention. For this update we searched the Cochrane Effective Practice and Organisation of Care Group specialised register, MEDLINE and CINAHL, for the years 2006 to 2011. We also handsearched the Journal of Interprofessional Care (2006 to 2011), reference lists of all included studies, the proceedings of leading IPE conferences, and websites of IPE organisations. Randomised controlled trials (RCTs), controlled before and after (CBA) studies and interrupted time series (ITS) studies of IPE interventions that reported objectively measured or self reported (validated instrument) patient/client or healthcare process outcomes. At least two review authors independently assessed the eligibility of potentially relevant studies. For included studies, at least two review authors extracted data and assessed study quality. A meta-analysis of study outcomes was not possible due to heterogeneity in study designs and outcome measures. Consequently, the results are presented in a narrative format. This update located nine new studies, which were added to the six studies from our last update in 2008. This review now includes 15 studies (eight RCTs, five CBA and two ITS studies). All of these studies measured the effectiveness of IPE interventions compared to no educational intervention. Seven studies indicated that IPE produced positive outcomes in the following areas: diabetes care, emergency department culture and patient satisfaction; collaborative team behaviour and reduction of clinical error rates for emergency department teams; collaborative team behaviour in operating rooms; management of care delivered in cases of domestic violence; and mental health practitioner competencies related to the delivery of patient care. In addition, four of the studies reported mixed outcomes (positive and neutral) and four studies reported that the IPE interventions had no impact on either professional practice or patient care. This updated review reports on 15 studies that met the inclusion criteria (nine studies from this update and six studies from the 2008 update). Although these studies reported some positive outcomes, due to the small number of studies and the heterogeneity of interventions and outcome measures, it is not possible to draw generalisable inferences about the key elements of IPE and its effectiveness. To improve the quality of evidence relating to IPE and patient outcomes or healthcare process outcomes, the following three gaps will need to be filled: first, studies that assess the effectiveness of IPE interventions compared to separate, profession-specific interventions; second, RCT, CBA or ITS studies with qualitative strands examining processes relating to the IPE and practice changes; third, cost-benefit analyses.
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                Author and article information

                Journal
                Front Psychiatry
                Front Psychiatry
                Front. Psychiatry
                Frontiers in Psychiatry
                Frontiers Media S.A.
                1664-0640
                22 January 2013
                2013
                : 4
                : 1
                Affiliations
                [1] 1Department of Medicine, University of Illinois at Chicago Chicago, IL, USA
                [2] 2Department of Pharmacology, University of Illinois at Chicago Chicago, IL, USA
                [3] 3Department of Biobehavioral Health Science, University of Illinois at Chicago Chicago, IL, USA
                Author notes

                Edited by: David Gozal, University of Chicago, USA

                Reviewed by: Patrick J. Strollo, University of Pittsburgh, USA; Josep M. Montserrat, University Hospital Clínic de Barcelona, Spain; Sina A. Gharib, University of Washington, USA; Malcolm Kohler, University Hospital of Zurich, Switzerland

                *Correspondence: David W. Carley, Department of Biobehavioral Health Science, University of Illinois at Chicago, 215W CON MC 802, 845 S Damen Ave, Chicago, IL, 60612, USA. e-mail: dwcarley@ 123456uic.edu

                Bharati Prasad, Miodrag G. Radulovacki and David W. Carley have contributed equally to this work.

                This article was submitted to Frontiers in Sleep Disorders, a specialty of Frontiers in Psychiatry.

                Article
                10.3389/fpsyt.2013.00001
                3550518
                23346060
                87b5efad-96da-44e5-849a-c733a83c5fae
                Copyright © 2013 Prasad, Radulovacki and Carley.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

                History
                : 09 November 2012
                : 02 January 2013
                Page count
                Figures: 1, Tables: 2, Equations: 0, References: 17, Pages: 5, Words: 3571
                Categories
                Psychiatry
                Original Research

                Clinical Psychology & Psychiatry
                apnea,clinical trial,dronabinol,drug treatment,osa,placebo-controlled,randomized

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