Infliximab and ciclosporin are of similar efficacy in treating acute severe ulcerative colitis, but there has been no comparative evaluation of their relative clinical effectiveness and cost-effectiveness. In this mixed methods, open-label, pragmatic randomised trial, we recruited consenting patients aged 18 years or older at 52 district general and teaching hospitals in England, Scotland, and Wales who had been admitted, unscheduled, with severe ulcerative colitis and failed to respond to intravenous hydrocortisone within about 5 days. Patients were randomly allocated (1:1) to receive either infliximab (5 mg/kg intravenous infusion given over 2 h at baseline, and again at 2 weeks and 6 weeks after the first infusion) or ciclosporin (2 mg/kg per day by continuous infusion for up to 7 days, followed by twice-daily tablets delivering 5·5 mg/kg per day for 12 weeks). Randomisation used a web-based password-protected site, with a dynamic algorithm to generate allocations on request, thus protecting against investigator preference or other subversion, while ensuring that each trial group was balanced by centre, which was the only stratification used. Local investigators and participants were aware of the treatment allocated, but the chief investigator and analysts were masked. Analysis was by treatment allocated. The primary outcome was quality-adjusted survival—ie, the area under the curve (AUC) of scores from the Crohn's and Ulcerative Colitis Questionnaire (CUCQ) completed by participants at baseline, 3 months, and 6 months, then every 6 months from 1 year to 3 years. This trial is registered with the ISRCTN Registry, number ISRCTN22663589. Between June 17, 2010, and Feb 26, 2013, 270 patients were recruited. 135 patients were allocated to the infliximab group and 135 to the ciclosporin group. 121 (90%) patients in each group were included in the analysis of the primary outcome. There was no significant difference between groups in quality-adjusted survival (mean AUC 564·0 [SD 241·9] in the infliximab group vs 587·0 [226·2] in the ciclosporin group; mean adjusted difference 7·9 [95% CI −22·0 to 37·8]; p=0·603). Likewise, there were no significant differences between groups in the secondary outcomes of CUCQ scores, EQ-5D, or SF-6D scores; frequency of colectomy (55 [41%] of 135 patients in the infliximab group vs 65 [48%] of 135 patients in the ciclosporin group; p=0·223); or mean time to colectomy (811 [95% CI 707–912] days in the infliximab group vs 744 [638–850] days in the ciclosporin group; p=0·251). There were no differences in serious adverse reactions (16 reactions in 14 participants receiving infliximab vs ten in nine patients receiving ciclosporin); serious adverse events (21 in 16 patients vs 25 in 17 patients); or deaths (three in the infliximab group vs none in the ciclosporin group). There was no significant difference between ciclosporin and infliximab in clinical effectiveness. NIHR Health Technology Assessment programme.

In response to recent advancements in inflammatory bowel disease (IBD) management, the British Society of Gastroenterology (BSG) Clinical Services and Standards Committee (CSSC) has commissioned the BSG IBD section to update its guidelines, last revised in 2019. These updated guidelines aim to complement the IBD standards and promote the use of the national primary care diagnostic pathway for lower gastrointestinal symptoms to enhance diagnostic accuracy and timeliness. Formulated through a systematic and transparent process, this document reflects a consensus of best practices based on current evidence. The guideline, while developed primarily for the UK, is structured to support IBD management internationally. It is endorsed by the BSG executive board and CSSC without external commercial funding, with involvement primarily supported through professional roles in public institutions and the National Health Service (NHS). Methodological revisions since the prior guidelines have enhanced rigor in technical review and development, with methodology details published independently following peer review. In developing the recommendations, 89 clinical experts and stakeholders participated in an online survey, identifying primary outcomes, such as clinical and endoscopic remission, as well as adverse event metrics, all stratified by clinically relevant effect sizes. These guidelines are intended to support clinical decision-making but are not prescriptive, recognizing that individual clinical scenarios may warrant tailored approaches. Further research may inform future revisions as new evidence emerges.

Background and aim:Several measures have been developed to assess the health-related quality of life [HRQoL] of patients with inflammatory bowel disease [IBD]. Our aim is to systematically review the HRQoL measures specific for patients with IBD and to appraise their measurement properties and methodological quality.Methods:We searched the PubMed, Embase, and PsycINFO databases for original articles describing the development and/or evaluation of one or more of the measurement properties [e.g. internal consistency, reliability, validity, responsiveness] of HRQoL measures specific for IBD. We assessed the measurement properties and examined the methodological quality of the measurement properties of each instrument using a standardized checklist.Results:We examined the full text of 75 articles that we deemed potentially eligible and identified 10 disease-specific HRQoL measures in IBD that covered different aspects of patients’ lives. Internal consistency, construct validity, and content validity were the commonly evaluated measurement properties. Seven HRQoL measures scored positive for at least four of eight measurement properties. The majority of studies were rated as ‘fair’ to ‘poor’ when assessing their methodology quality. The most established HRQoL measure in the literature was the Inflammatory Bowel Disease Questionnaire [IBDQ].Conclusions:Most of the included HRQoL measures did not include all the required measurement properties or had a problem with their methodological quality. The most widely used and validated measure was the IBDQ. Further validation studies are required to support the use of other HRQoL measures.

Gastrointestinal illnesses cause physical, emotional and social impact on patients. Patient reported outcome measures (PROMs) are increasingly used in clinical decision‐making, clinical research and approval of new therapies. In the last decade, there has been a rapid increase in the number of PROMs in gastroenterology and, therefore, the choice between which of these PROMs to use can be difficult. Not all PROM instruments currently used in research and clinical practice in gastroenterology have gone through a rigorous development methodology. New drugs and therapies will not have access to the market if the PROMs used in their clinical trials are not validated according to the guidelines of the international agencies. Therefore, it is important to know the required properties of PROMs when choosing or evaluating a drug or a clinical intervention. This paper reviews the current literature on how to assess the validity and reliability of PROMs. It summarises the required properties into a practical guide for gastroenterologists to use in assessing an instrument for use in clinical practice or research.

Replacing skin defects has witnessed several developments over the centuries. It started with the introduction of skin grafting by Reverdin in 1871. Since then, varieties of skin grafting techniques have been used successfully. Despite being clinically useful, skin grafts have many limitations including the availability of the donor site especially in circumstances of extensive skin loss, immune rejection in allogenic skin grafts, pain, scarring, slow healing and infection.(1,2) For these reasons, scientist have worked hard to find skin substitutes to replace skin defects without the need for a "natural" skin graft. These materials which are used to cover skin defects are called "Skin substitutes". This article briefly discusses the common types of skin substitutes and their clinical uses.

Background: The efficacy of infliximab and ciclosporin in treating severe ulcerative colitis (UC) is proven, but there has been no comparative evaluation of effectiveness.Objective: To compare the clinical effectiveness and cost-effectiveness of infliximab and ciclosporin in treating steroid-resistant acute severe UC.Method: Between May 2010 and February 2013 we recruited 270 participants from 52 hospitals in England, Scotland and Wales to an open-label parallel-group, pragmatic randomised trial. Consented patients admitted with severe colitis completed baseline quality-of-life questionnaires before receiving intravenous hydrocortisone. If they failed to respond within about 5 days, and met other inclusion criteria, we invited them to participate and used a web-based adaptive randomisation algorithm to allocate them in equal proportions between 5 mg/kg of intravenous infliximab at 0, 2 and 6 weeks or 2 mg/kg/day of intravenous ciclosporin for 7 days followed by 5.5 mg/kg/day of oral ciclosporin until 12 weeks from randomisation. Further treatment was at the discretion of physicians responsible for clinical management. The primary outcome was quality-adjusted survival (QAS): the area under the curve (AUC) of scores derived from Crohn’s and Ulcerative Colitis Questionnaires completed by participants at 3 and 6 months, and then 6-monthly over 1–3 years, more frequently after surgery. Secondary outcomes collected simultaneously included European Quality of Life-5 Dimensions (EQ-5D) scores and NHS resource use to estimate cost-effectiveness. Blinding was possible only for data analysts. We interviewed 20 trial participants and 23 participating professionals. Funded data collection finished in March 2014. Most participants consented to complete annual questionnaires and for us to analyse their routinely collected health data over 10 years.Results: The 135 participants in each group were well matched at baseline. In 121 participants analysed in each group, we found no significant difference between infliximab and ciclosporin in QAS [mean difference in AUC/day 0.0297 favouring ciclosporin, 95% confidence interval (CI) –0.0088 to 0.0682;p = 0.129]; EQ-5D scores (quality-adjusted life-year mean difference 0.021 favouring ciclosporin, 95% CI –0.032 to 0.096;p = 0.350); Short Form questionnaire-6 Dimensions scores (mean difference 0.0051 favouring ciclosporin, 95% CI –0.0250 to 0.0353;p = 0.737). There was no statistically significant difference in colectomy rates [odds ratio (OR) 1.350 favouring infliximab, 95% CI 0.832 to 2.188;p = 0.223]; numbers of serious adverse reactions (event ratio = 0.938 favouring ciclosporin, 95% CI 0.590 to 1.493;p = 0.788); participants with serious adverse reactions (OR 0.660 favouring ciclosporin, 95% CI 0.282 to 1.546;p = 0.338); numbers of serious adverse events (event ratio 1.075 favouring infliximab, 95% CI 0.603 to 1.917;p = 0.807); participants with serious adverse events (OR 0.999 favouring infliximab, 95% CI 0.473 to 2.114;p = 0.998); deaths (all three who died received infliximab;p = 0.247) or concomitant use of immunosuppressants. The lower cost of ciclosporin led to lower total NHS costs (mean difference –£5632, 95% CI –£8305 to –£2773;p < 0.001). Interviews highlighted the debilitating effect of UC; participants were more positive about infliximab than ciclosporin. Professionals reported advantages and disadvantages with both drugs, but nurses disliked the intravenous ciclosporin.Conclusions: Total cost to the NHS was considerably higher for infliximab than ciclosporin. Nevertheless, there was no significant difference between the two drugs in clinical effectiveness, colectomy rates, incidence of SAEs or reactions, or mortality, when measured 1–3 years post treatment. To assess long-term outcome participants will be followed up for 10 years post randomisation, using questionnaires and routinely collected data. Further studies will be needed to evaluate the efficacy and effectiveness of new anti-tumour necrosis factor drugs and formulations of ciclosporin.Trial registration: Current Controlled Trials ISRCTN22663589.Funding: This project was funded by the NIHR Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 20, No. 44. See the NIHR Journals Library website for further project information.