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

Introduction: Cognitive 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. Methods: We 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. Results: The 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. Conclusion: We 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 registration: https://www.clinicaltrials.gov/study/NCT04990765?cond=addiction%20CRAVR&rank=2, identifier NCT05042180.

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.

Topical brimonidine reduces IPL-induced erythema without affecting efficacy: A randomized controlled trial in patients with facial telangiectasias.

BACKGROUND: Laser and intense pulsed light (IPL) are standard symptomatic treatments for superficial telangiectasias, but postoperative erythema, oedema, and pain may prolong downtime. OBJECTIVES: To investigate whether topical brimonidine reduces IPL-induced inflammation in patients with moderate to severe facial telangiectasias. METHODS: A randomized, two-centre, single-blinded, split-face trial on adjuvant brimonidine and air-cooling versus air-cooling alone (control) in 19 patients treated in Denmark (n = 10 patients) and Belgium (n = 9). Brimonidine was applied to the allocated side after each of three facial IPL-treatments, given at 3-week intervals. Patients were assessed up to 1 month after the final treatment. Outcome measures included blinded clinical on-site evaluation of erythema and oedema (5-point-scales), objective erythema-scores (red-filter analysis), patient-evaluated pain (Visual Analogue Scale), IPL-efficacy (blinded photo-evaluation of telangiectasia clearance), and patient preference. RESULTS: In total, 19 patients were enrolled and completed the study. IPL induced moderate to severe erythema after each treatment. Application of brimonidine, reduced erythema to baseline values compared to air-cooling alone and sustained efficacy 24 hours after treatment (median difference reduction: score 1 at each assessment, P ≤ 0.022). Objective erythema-scores supported clinical findings, demonstrating a median erythema reduction of 50-95% after application of brimonidine and air-cooling compared to 9-28% reduction after air-cooling alone (P ≥ 0.002). No difference in reduction of IPL-induced oedema was observed between facial sides (P ≥ 0.227). Brimonidine and air-cooling slightly and consistently reduced postoperative pain compared to air-cooling alone (VAS 1.0 after brimonidine versus VAS 1.5-2.0 after air-cooling alone at treatment 1-3, P ≤ 0.032). At 1-month follow-up, patients experienced excellent clearance of telangiectasias (75-100% clearance) on both facial sides (P = 1.000). Patient preference supported clinical data and 79% of patients preferred brimonidine to control (P = 0.019). CONCLUSION: Compared to air-cooling alone, adjuvant brimonidine reduces IPL-induced erythema and associated pain while maintaining a high IPL-efficacy. Lasers Surg. Med. 50:1002-1009, 2018. © 2018 Wiley Periodicals, Inc.

Skin reactions after photodynamic therapy are unaffected by 839 nm photobiomodulation therapy: A randomized, double-blind, placebo-controlled, clinical trial.

BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) is associated with erythema and edema. Photobiomodulation (PBM) therapy may stimulate the skin recovery process. We investigated the potential of PBM to reduce PDT-induced skin reactions. STUDY DESIGN AND METHODS: Healthy volunteers (n = 20) were randomized to receive left- or right side PBM (near-infrared 839/595 nm) or placebo-PBM (595 nm) on their buttocks. Corresponding test areas were exposed to standardized PDT reactions, using ablative fractional laser-assisted PDT (AFXL-PDT) with methyl-aminolevulinate (MAL) incubated for 30, 90, and 180 minutes before red-light illumination. Each buttock received PBM and placebo-PBM for five consecutive days, starting one day before PDT interventions. Follow-up visits were performed 4 and 11 days after PDT. Outcome measure included blinded, observer-assessed skin reactions, substantiated by objectively measured erythema and pigment percentages and skin temperatures. RESULTS: PDT interventions induced a standardized range of erythema and edema in all subjects. Skin reactions were clinically unaffected by PBM throughout the active treatment period and at all subsequent follow-up visits (PBM vs. placebo-PBM, P = 1.000). Clinical results were supported by similar erythema intensities and skin temperatures in PBM and placebo-PBM treated skin: median erythema 28.1% versus 30.3% (AFXL-PDT with 30 minutes MAL-incubation), 36.1% versus 35.2% (90 minutes MAL-incubation) and 39.4% versus 40.9% (180 minutes MAL-incubation) (Day 4, P > 0.05). No differences in clinical hyperpigmentation or pigment percentages were observed between corresponding test areas in any subject on the final 11-day follow-up. CONCLUSION: Under the current study conditions, PDT-induced skin reactions were unaffected by PBM. Lasers Surg. Med. 49:810-818, 2017. © 2017 Wiley Periodicals, Inc.

Topically applied methotrexate is rapidly delivered into skin by fractional laser ablation.

OBJECTIVES: Methotrexate (MTX) is a chemotherapeutic and anti-inflammatory drug that may cause systemic adverse effects. This study investigated kinetics and biodistribution of MTX delivered topically by ablative fractional laser (AFXL). METHODS: In vitro passive diffusion of 10 mg/ml MTX (1 w/v%) was measured from 0.25 to 24 h through AFXL-processed and intact porcine skin in Franz Cells (n = 46). A 2,940 nm fractional Erbium Yttrium Aluminium Garnet laser generated mid-dermal microchannels at 2.4% density, and 256 mJ/microchannel. HPLC quantified MTX-concentrations in extracts from mid-dermal skin sections, donor and receiver compartments. Fluorescence microscopy of UVC-activated MTX-fluorescence and desorption electro-spray ionization mass spectrometry imaging (DESI-MSI) evaluated MTX biodistribution. RESULTS: AFXL-processed skin facilitated rapid MTX delivery through cone-shaped microchannels of 690 µm ablation depth, lined by the 47 µm thermal coagulation zone (CZ). Quantitatively, MTX was detectable by HPLC in mid-dermis after 15 min, significantly exceeded deposition in intact skin after 1.5 h, and saturated skin after 7 h at a 10-fold increased MTX-deposition versus intact skin (3.08 vs 0.30 mg/cm(3), p = 0.002). Transdermal permeation was < 1.5% of applied MTX before skin saturation, and increased up to 8.0% after 24 h. Qualitatively, MTX distributed into CZ within 15 min (p = 0.015) and further into surrounding dermal tissue after 1.5 h (p = 0.004). After skin saturation at 7 h, MTX fluorescence intensities in CZ and tissue were similar and DESI-MSI confirmed MTX biodistribution throughout the mid-dermal skin section. CONCLUSIONS: MTX absorbs rapidly into mid-dermis of AFXL-processed skin with minimal transdermal permeation until skin saturation, suggesting a possible alternative to systemic MTX for some skin disorders.