BACKGROUND:Gabapentin is an anticonvulsant medication with approval for use in neuropathic pain and epileptic disorders. It is frequently added to multimodal analgesic regimens during and after surgery to reduce opioid use while controlling pain effectively. There is little evidence to show its effectiveness in major surgery. METHODS:In this multicenter, double-blinded randomized controlled trial, adults undergoing major cardiac, thoracic, or abdominal surgery were randomized to receive either gabapentin (600 mg before surgery, 300 mg twice daily for 2 days after surgery) or placebo. The primary outcome was length of hospital stay. Secondary outcomes included acute and chronic pain, total opioid use, adverse health events, and health-related quality of life. Patients were followed up daily in-hospital until discharge and then at 4 weeks and 4 months after surgery. RESULTS:A total of 1,196 participants were randomized (500 underwent cardiac, 346 thoracic, and 350 abdominal surgery); 596 were allocated to placebo, and 600 were allocated to gabapentin. Median length of hospital stay was similar in the two groups (gabapentin, 5.94 [interquartile range (IQR), 4.08 to 8.04] days; placebo, 6.15 [IQR, 4.22 to 8.97] days; hazard ratio, 1.07; 95% CI, 0.95 to 1.20; P = 0.26). Overall, 384 participants experienced one or more serious adverse events (gabapentin, 189 of 596 [31.7%]; placebo, 195 of 599 [32.6%]), with some variation across surgical specialties. CONCLUSIONS:Among patients undergoing major cardiac, thoracic, and abdominal surgery, adding gabapentin to multimodal analgesic regimes did not alter the length of hospital stay or the number of serious adverse events.

IntroductionDepression is three to four times more prevalent in autistic people and is related to reduced quality of life. There is a need for empirically supported psychological interventions for depression specifically adapted to meet the needs of autistic adults. ADEPT-2 aims to establish the clinical and cost-effectiveness of an adapted low-intensity psychological intervention (guided self-help) for depression in autistic adults.Methods and analysisA two parallel-group multicentre pragmatic randomised controlled trial investigating the effectiveness of GSH for depression in autistic adults. Participants (n=248) aged ≥18 years with a clinical diagnosis of autism currently experiencing depression will be randomised to GSH or treatment as usual (TAU). GSH is a low-intensity psychological intervention based on the principles of behavioural activation adapted for autism. GSH comprises informational materials for nine individual sessions facilitated online by a GSH coach who has received training and supervision in delivering the intervention. The primary outcome will be Beck Depression Inventory-II depression scores at 16 weeks post randomisation with follow-up measures at 32 and 52 weeks. Additional measures of anxiety, patient-rated global improvement, quality of life, work and social adjustment, positive and negative affect will be measured 16 and 52 weeks post randomisation. The primary health economic analysis will assess the cost-effectiveness of GSH compared with TAU over 52 weeks, from a societal perspective including the National Health Service, personal social services, personal expenses, voluntary services and productivity. An embedded qualitative study will explore the acceptability, experiences and adherence of participants and therapists to treatment principles.Ethics and disseminationThis trial has been approved by the East of England - Essex Research Ethics Committee on 10 June 2022 (REC Reference number: 22/EE/0091). The findings of the research will be submitted for publication in peer-reviewed journals and disseminated in an appropriate format to trial participants and the wider public.Trial registration numberISRCTN17547011.

BackgroundThere is limited randomized evidence on the comparative outcomes of early-stage lung cancer resection by video-assisted thoracoscopic surgery (VATS) versus open resection.MethodsWe conducted a parallel-group multicenter randomized trial that recruited participants with known or suspected early-stage lung cancer and randomly assigned them to open or VATS resection of their lesions. The primary outcome was physical function at 5 weeks as a measure of recovery using the European Organisation for Research and Treatment of Cancer core health-related quality of life questionnaire (QLQ-C30) (scores range from 0 to 100, with higher scores indicating better function; the clinical minimally important difference for improvement is 5 points). We followed the patients for an additional 47 weeks for other outcomes.ResultsA total of 503 participants were randomly assigned (247 to VATS and 256 to open lobectomy). At 5 weeks, median physical function was 73 in the VATS group and 67 in the open surgery group, with a mean difference of 4.65 points (95% confidence interval, 1.69 to 7.61). Of the participants allocated to VATS, 30.7% had serious adverse events after discharge compared with 37.8% of those allocated to open surgery (risk ratio, 0.81 [95% confidence interval, 0.66 to 1.00]). At 52 weeks, there were no differences in cancer progression-free survival (hazard ratio, 0.74 [0.43 to 1.27]) or overall survival (hazard ratio, 0.67 [0.32 to 1.40]).ConclusionsVATS lobectomy for lung cancer is associated with a better recovery of physical function in the 5 weeks after random assignment compared with open surgery. Long-term oncologic outcomes will require continued follow-up to assess. (Funded by the National Institute for Health Research Health Technology Assessment programme [reference number 13/04/03]; ISRCTN number, ISRCTN13472721.) In a patient with early-stage lung cancer, is resection by video-assisted thoracoscopic surgery (VATS) versus open resection superior with respect to the postoperative recovery? This question was addressed in a multicenter randomized trial in more than 500 patients. At 5 weeks after surgery, the physical function mean score was 73 in the VATS group and 67 in the open surgery group (function scores range from 0 to 100, with higher scores indicating better function). Of the participants allocated to VATS, 30.7% had serious adverse events after discharge compared with 37.8% of those allocated to open surgery. At 52 weeks, there were no differences in cancer progression-free survival.

Objectives Lung cancer is the leading cause of cancer death, and has the highest economic burden across Europe of all cancers. Early-stage disease is predominantly treated with surgery, and lung cancer resection using a video-assisted thoracoscopic surgery (VATS) approach has increased, despite limited randomised evidence of its effectiveness and cost-effectiveness compared to open lobectomy. The VIOLET randomised controlled trial compared VATS lobectomy with open surgery in participants with known or suspected (cT1-3, N0-1, M0) lung cancer recruited from nine UK centres. We report the trial cost-effectiveness analysis. Methods A within-trial cost-effectiveness analysis of VATS versus open lobectomy was conducted, with a one year time horizon, from a UK National Health Service and personal social services perspective. The primary outcome measure was quality-adjusted life years (QALYs), estimated using the EQ-5D-5L questionnaire. Results Mean QALYs to one year were 0.841 and 0.780 in the VATS and open groups respectively, (a statistically significant mean difference (MD) of +0.060, 95% CI +0.029, +0.092). Total costs of care were £10,879 and £13,581 in the VATS and open groups, (MD= -£2,702, 95% CI –£5,632, +£228). Differences in costs and QALYs favoured VATS, and when combined, resulted in VATS being clearly cost-effective. The probability that VATS is cost-effective at a willingness-to-pay threshold of £20,000 per QALY is >0.99, indeed VATS is considered cost-effective at any threshold, with negligible uncertainty around this finding. Conclusions VATS lobectomy provides good value for money. When considered alongside the published clinical findings from VIOLET that multiple outcomes were significantly improved with VATS, the policy implications are clear: VATS should be the first choice for suitable patients with early-stage lung cancer. ISRCTN13472721

BACKGROUND:Lung cancer is the leading cause of cancer death. Surgery remains the main method of managing early-stage disease. Minimal-access video-assisted thoracoscopic surgery results in less tissue trauma than open surgery; however, it is not known if it improves patient outcomes. OBJECTIVE:To compare the clinical effectiveness and cost-effectiveness of video-assisted thoracoscopic surgery lobectomy with open surgery for the treatment of lung cancer. DESIGN, SETTING AND PARTICIPANTS:A multicentre, superiority, parallel-group, randomised controlled trial with blinding of participants (until hospital discharge) and outcome assessors conducted in nine NHS hospitals. Adults referred for lung resection for known or suspected lung cancer, with disease suitable for both surgeries, were eligible. Participants were followed up for 1 year. INTERVENTIONS:Participants were randomised 1 : 1 to video-assisted thoracoscopic surgery lobectomy or open surgery. Video-assisted thoracoscopic surgery used one to four keyhole incisions without rib spreading. Open surgery used a single incision with rib spreading, with or without rib resection. MAIN OUTCOME MEASURES:The primary outcome was self-reported physical function (using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30) at 5 weeks. Secondary outcomes included upstaging to pathologic node stage 2 disease, time from surgery to hospital discharge, pain in the first 2 days, prolonged pain requiring analgesia at > 5 weeks, adverse health events, uptake of adjuvant treatment, overall and disease-free survival, quality of life (Quality of Life Questionnaire Core 30, Quality of Life Questionnaire Lung Cancer 13 and EQ-5D) at 2 and 5 weeks and 3, 6 and 12 months, and cost-effectiveness. RESULTS:A total of 503 patients were randomised between July 2015 and February 2019 (video-assisted thoracoscopic surgery, n = 247; open surgery, n = 256). One participant withdrew before surgery. The mean age of patients was 69 years; 249 (49.5%) patients were men and 242 (48.1%) did not have a confirmed diagnosis. Lobectomy was performed in 453 of 502 (90.2%) participants and complete resection was achieved in 429 of 439 (97.7%) participants. Quality of Life Questionnaire Core 30 physical function was better in the video-assisted thoracoscopic surgery group than in the open-surgery group at 5 weeks (video-assisted thoracoscopic surgery, n = 247; open surgery, n = 255; mean difference 4.65, 95% confidence interval 1.69 to 7.61; p = 0.0089). Upstaging from clinical node stage 0 to pathologic node stage 1 and from clinical node stage 0 or 1 to pathologic node stage 2 was similar (p ≥ 0.50). Pain scores were similar on day 1, but lower in the video-assisted thoracoscopic surgery group on day 2 (mean difference -0.54, 95% confidence interval -0.99 to -0.09; p = 0.018). Analgesic consumption was 10% lower (95% CI -20% to 1%) and the median hospital stay was less (4 vs. 5 days, hazard ratio 1.34, 95% confidence interval 1.09, 1.65; p = 0.006) in the video-assisted thoracoscopic surgery group than in the open-surgery group. Prolonged pain was also less (relative risk 0.82, 95% confidence interval 0.72 to 0.94; p = 0.003). Time to uptake of adjuvant treatment, overall survival and progression-free survival were similar (p ≥ 0.28). Fewer participants in the video-assisted thoracoscopic surgery group than in the open-surgery group experienced complications before and after discharge from hospital (relative risk 0.74, 95% confidence interval 0.66 to 0.84; p < 0.001 and relative risk 0.81, 95% confidence interval 0.66 to 1.00; p = 0.053, respectively). Quality of life to 1 year was better across several domains in the video-assisted thoracoscopic surgery group than in the open-surgery group. The probability that video-assisted thoracoscopic surgery is cost-effective at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year is 1. LIMITATIONS:Ethnic minorities were under-represented compared with the UK population (< 5%), but the cohort reflected the lung cancer population. CONCLUSIONS:Video-assisted thoracoscopic surgery lobectomy was associated with less pain, fewer complications and better quality of life without any compromise to oncologic outcome. Use of video-assisted thoracoscopic surgery is highly likely to be cost-effective for the NHS. FUTURE WORK:Evaluation of the efficacy of video-assisted thoracoscopic surgery with robotic assistance, which is being offered in many hospitals. TRIAL REGISTRATION:This trial is registered as ISRCTN13472721. FUNDING:This project was funded by the National Institute for Health and Care Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 48. See the NIHR Journals Library website for further project information.

8504 Background: Video assisted thoracoscopic surgery (VATS) is a popular access for lung cancer resection. However, there is limited information from RCTs from in-hospital to one-year clinical efficacy, safety and oncologic outcomes of a minimal access approach. Methods: VIOLET is a parallel group multi-center RCT conducted in 9 centers in the United Kingdom that recruited participants with known or suspected (cT1-3, N0-1 and M0) lung cancer (ISRCTN13472721). Trial protocol: https://bmjopen.bmj.com/content/9/10/e029507.info. Results: From July 2015 to February 2019, 503 participants were randomized to VATS (n=247) or open (n=256) lobectomy. Patients allocated to VATS had less pain with a mean difference (MD) in visual analogue score of -0.54 (95%CI -0.99 to -0.10) despite less analgesic consumption (mean ratio 0.90, 95%CI 0.80 to 1.01). After discharge pain was consistent on multiple sub-scales including overall pain (MD -7.19, -10.59 to -3.80), chest pain (MD -4.66, -7.96 to -1.36) and an 18% relative risk (RR) reduction in incision pain (RR 0.82; 0.72 to 0.94) up to one-year. Better functional recovery continued in VATS arm after discharge with better physical function (primary outcome) with MD of 4.65 (1.69 to 7.61; P=0.002) at 5 weeks and overall improvement in global health status with a MD of 4.21 (1.62 to 6.79; P=0.001). In hospital, VATS arm had fewer complications (RR 0.74, 0.66 to 0.84; P<0.001) with no difference in serious adverse events (RR 0.98, 0.59 to 1.63; P=0.948). Median hospital stay was one day shorter in the VATS arm (4 vs 5 days) corresponding to hazard ratio (HR) for discharge of 1.34, 95%CI 1.09 to 1.65; P=0.006). After discharge VATS arm had 19% less serious adverse events (RR 0.81, 0.66 to 1.00; p=0.053) and lower readmission rates (29.0% vs. 35.9% respectively) to one-year. Of those with lymph node disease, 50.9% in the VATS and 45.9% in open arms received adjuvant treatment. There was no difference in the time to uptake of adjuvant chemotherapy (HR 1.12, 0.62 to 2.02; p=0.716). Recurrence with clinical follow up and CT at one-year was similar with 7.7% versus 8.1% in the VATS and open groups respectively. Progression-free survival (HR 0.74, 0.43 to 1.27; p=0.27) and overall survival HR 0.67, 0.32 to 1.40; p=0.282) was not significantly different. Conclusions: VATS lobectomy for lung cancer is associated with less pain, fewer in-hospital complications and shorter hospital stay, achieved without any compromise to early oncologic outcomes nor serious adverse events. Superior functional recovery continues in the post-operative period with improved physical function, lower re-admission rates and no difference in disease-free and overall survival up to one-year. Clinical trial information: ISRCTN13472721.

Introduction Gabapentin is an antiepileptic drug currently licensed to treat epilepsy and neuropathic pain but has been used off-label to treat acute postoperative pain. The GAP study will compare the effectiveness, cost-effectiveness and safety of gabapentin as an adjunct to standard multimodal analgesia versus placebo for the management of pain after major surgery. Methods and analysis The GAP study is a multicentre, double-blind, randomised controlled trial in patients aged 18 years and over, undergoing different types of major surgery (cardiac, thoracic or abdominal). Patients will be randomised in a 1:1 ratio to receive either gabapentin (600 mg just before surgery and 600 mg/day for 2 days after surgery) or placebo in addition to usual pain management for each type of surgery. Patients will be followed up daily until hospital discharge and then at 4 weeks and 4 months after surgery. The primary outcome is length of hospital stay following surgery. Secondary outcomes include pain, total opioid use, adverse health events, health related quality of life and costs. Ethics and dissemination This study has been approved by the Research Ethics Committee . Findings will be shared with participating hospitals and disseminated to the academic community through peer-reviewed publications and presentation at national and international meetings. Patients will be informed of the results through patient organisations and participant newsletters. Trial registration number ISRCTN63614165.