Virtual reality-assisted cognitive behavioural therapy for outpatients with alcohol use disorder (CRAVR):A protocol for a randomised controlled trial

Introduction Alcohol use disorder (AUD) is a brain disorder linked to over 200 health conditions. Cognitive behavioural therapy (CBT) is considered the best practice in the treatment of AUD, but more than 60% of patients relapse within the first year after treatment. Psychotherapy combined with virtual reality (VR) has received increasing interest in the treatment of AUD. However, existing studies have primarily investigated the use of VR for cue reactivity. We therefore aimed to investigate the effect of VR-assisted CBT (VR-CBT). Methods and analysis This study is an assessor-blinded, randomised clinical trial being conducted at three outpatient clinics in Denmark. We will randomise 102 patients to 14 individual sessions of either manualised VR-CBT or CBT. The VR-CBT group will receive exposure to immersive high-risk VR situations from a pub, bar/party, restaurant, supermarket and at-home (30 videos) to activate high-risk-related beliefs and cravings for subsequent modification using CBT techniques. The treatment period is 6 months, and follow-up visits will be performed 3, 6, 9 and 12 months after inclusion. The primary outcome measure is the change in total alcohol consumption from baseline to 6 months after inclusion, measured with the Timeline Followback Method. Key secondary outcome measures include changes in the number of heavy drinking days, alcohol cravings, cognition, and symptoms of depression and anxiety. Ethics and dissemination Approval has been obtained by the research ethics committee in the Capital Region of Denmark (H-20082136) and the Danish Data Protection Agency (P-2021-217). All patients will receive both oral and written information about the trial and written informed consent will be obtained from each patient before inclusion. The study results will be disseminated in peer-reviewed publications and conference presentations. Trial registration number ClinicalTrial.gov, NCT05042180.</p

第994回千葉医学会例会・千葉大学医学部第二外科例会

BACKGROUND AND AIM:Ingenol mebutate (IngMeb) is an effective treatment for actinic keratosis. In this study, we hypothesized that repeated treatments with IngMeb may prevent progression of UV-induced photodamage, and that concurrent application of a corticosteroid may reduce IngMeb-induced local skin responses (LSR). METHODS:Hairless mice (n = 60; 3 groups of 20 mice) were irradiated with solar simulated ultraviolet radiation (UVR) throughout the study. Five single treatments with IngMeb were given at 4-week intervals (Days 21, 49, 77, 105, and 133). Clobetasol propionate (CP) was applied once daily for 5 days prior to each IngMeb application, as well as 6 h and 1 day post treatment. One week after IngMeb treatment No. 1, 3, and 5 (Days 28, 84, and 140), biopsies from four mice in each group were collected for histological evaluation of UV-damage on a standardized UV-damage scale (0-12). LSR (0-24) were assessed once daily (Days 1-7) after each IngMeb treatment. RESULTS:IngMeb prevented progression of photodamage in terms of keratosis grade, epidermal hypertrophy, dysplasia, and dermal actinic damage with a lower composite UV-damage score on day 140 (UVR 10.25 vs. UVR+IngMeb 6.00, p = 0.002) compared to UVR alone. IngMeb induced LSR, including erythema, flaking, crusting, bleeding, vesiculation, and ulceration. Concurrent CP increased LSR (max LSR Tx 1-5: UVR+IngMeb+CP 3.6-5.5 vs. UVR+IngMeb 2.6-4.3) and provided better prevention of photodamage compared to IngMeb alone (Day 140: UVR+IngMeb 6.00 vs. UVR+IngMeb+CP 3.00 p < 0.001). CONCLUSION:Repeated field-directed treatments with IngMeb prevent progression of cutaneous photodamage in hairless mice, while CP cannot be used to alleviate IngMeb-induced LSR. The findings suggest that IngMeb may potentially serve as a prophylactic treatment for UV-induced tumors

Virtual reality-assisted cognitive behavioral therapy for patients with alcohol use disorder: a randomized feasibility study

IntroductionCognitive behavioral therapy (CBT) is an evidence-based treatment for alcohol use disorder (AUD). Exposure to high-risk situations in virtual reality (VR) has been suggested to have a potential therapeutical benefit, but no previous study has combined VR and CBT for AUD. We aimed to investigate the feasibility of using VR-simulated high-risk environments in CBT-based treatment of AUD.MethodsWe randomized ten treatment-seeking AUD-diagnosed individuals to three sessions of conventional CBT or VR-assisted CBT performed at two outpatient clinics in Denmark. In each session, patients randomized to VR-CBT were exposed to VR-simulations from a restaurant to induce authentic thoughts, emotions, physiological reactions, and craving for CBT purposes. The primary outcome measure was feasibility: Drop-out rate, psychological reactions, and simulator sickness. Secondary outcomes were assessment of preliminary short-term changes in alcohol consumption and craving from baseline to one-week and one-month follow-up. In addition, the study was conducted for training in operationalization of VR equipment, treatment manuals, and research questionnaires.ResultsThe majority of patients completed all study visits (90%). VR induced authentic high-risk related thoughts, emotions, and physiological reactions that were considered relevant for CBT by patients and therapists. Four of five patients randomized to VR-CBT experienced cravings during VR simulations, and most of these patients (3/5) experienced mild simulator sickness during VR exposure. The preliminary data showed that patients receiving VR-CBT had more reduction in alcohol consumption than patients receiving conventional CBT at one week- (median 94% vs. 72%) and one-month follow-up (median 98% vs. 55%). Similar results were found regarding changes in cravings.ConclusionWe demonstrated VR-CBT to be a feasible intervention for patients with AUD which supports continued investigations in a larger randomized clinical trial evaluating the efficacy of VR-CBT.Clinical trial registrationhttps://www.clinicaltrials.gov/study/NCT04990765?cond=addiction%20CRAVR&amp;rank=2, identifier NCT05042180

Fractional laser-assisted drug uptake: impact of time-related topical application to achieve enhanced delivery

Background and Objective: Ablative fractional laser (AFXL) is acknowledged to increase uptake of topically applied agents in skin. AFXL channels gradually close over time, which may impair this capability. The time frame for applying a drug after AFXL exposure remains to be established. The aim of this study, was to investigate the importance of time-related topical application after AFXL exposure and to relate resultant uptake in skin with AFXL channel morphology and skin integrity. Study Design/Materials and Methods: Buttock skin of healthy volunteers (n = 11) was exposed to 10,600 nm fractional CO laser using 5% density, 120 μm beam diameter, 15 mJ pulse energy. Sodium fluorescein (NaF) a small, hydrophilic molecule (370 MW, log P = −1.52) was applied under standardized conditions at specific time points after laser exposure (0, 2, 5, 10, 30, 60, 90 minute, 6, 24, and 48 hours). Fluorescence photography collected fluorescence images up to 180 minute after NaF application. Optical coherence tomography (OCT) assessed AFXL channel dimensions and transepidermal water loss (TEWL) estimated loss of skin integrity. Results: Fluorescence intensities (FI) were significantly elevated when NaF was applied up to 6 hours after laser exposure compared to non-laser-processed skin (median FI 1947 arbitrary units [interquartile range 1,246–3,560] versus 1,004 [350–1,538], P 0.1). NaF application later than 30 minute after AFXL exposure resulted in gradually decreasing FI, becoming similar to intact skin when applied at 24–48 hours after AFXL exposure (P > 0.2). OCT images demonstrated that AFXL channels closed over time (100% [100–100%] open up to 30 minute, 75% [4–86%] at 6 hours and 3% [0–15%] at 24–48 hours after AFXL exposure). TEWL measurements proved loss of skin integrity up to 6 hours after AFXL exposure, while integrity was similar in laser-exposed and non-laser-exposed skin at 24–48 hours. Conclusions: The time frame to maintain enhanced drug delivery sustained for several hours after AFXL exposure, corresponding to channel morphology and loss of skin integrity. Lasers Surg. Med. 49:348–354, 2017