Background: Reducing health inequity is essential. The FAIRSTEPS (Framework to Address Inequities in pRimary care using STakEholder PerspectiveS) study developed and prioritised 28 vignettes describing complex primary care interventions targeted to disadvantaged groups, through Delphi consensus ranking by primary care practitioners for feasibility and perceived usefulness. Aim: To build on FAIRSTEPS by quantifying potential impacts of prioritised vignettes on costeffectiveness and health equity. Design & setting: Simplified distributional costeffectiveness analysis (DCEA) in England. Method: Pragmatic literature searches were carried out around each vignette to identify the following: (1) available economic evidence; and (2) information about size and distribution of populations targeted. Economic evidence was quality assessed using adapted National Institute for Health and Care Excellence (NICE) appraisal checklists. Extracted cost and quality-adjusted life-year (QALY) data and population data, were combined with published distributions of health opportunity costs and baseline lifetime health, to estimate net health benefits and equity measures for each vignette. Results: Suitable costeffectiveness evidence was identified for 17 of 28 vignettes, with variable study quality and applicability. Fourteen vignettes were both costeffective and equity-generating, with the most beneficial on both dimensions relating to community champions for health promotion; integrated care for people sleeping rough, engaged in sex work, or using drugs; and weight-loss programmes targeted at people on low incomes. Conclusion: Simplified DCEA using published data can be used to provide additional evidence to help prioritise complex primary care interventions aimed at disadvantaged populations, although the analysis is hindered by low quality economic data and limited study comparability. Further research estimating baseline health and health opportunity cost distributions across disadvantaged groups would improve accuracy of health equity assessments.

Background:Access to healthcare may be driving unplanned and potentially avoidable hospital admissions for people diagnosed with inflammatory bowel disease (IBD). Interventions to reduce unplanned and potentially avoidable admissions need to be developed based on a clear conceptual framework that identifies the system-level access barriers contributing to these admissions. This scoping review aimed to synthesize the health system components for reducing unplanned IBD admissions to develop a conceptual framework to guide future interventions for reducing unplanned admissions. Methods:A scoping review was conducted to identify literature exploring factors associated with unplanned IBD admissions and interventions to reduce IBD admissions. Literature published between January 2000 and October 2024 was identified from 4 electronic databases (Medline, Embase, CINAHL, and PubMed). A narrative synthesis presented the findings, guided by Candidacy Framework, to understand issues in healthcare access. Results and Conclusions:Of 1980 records identified, 17 were included. Avoidable IBD admissions result from inequity across the patient journey through healthcare, specifically in access to: (1) earlier intervention during a flare, (2) specialist clinical advice about symptoms and psychosocial issues, (3) rapid access to outpatient care, (4) patient education, (5) systems that support self-management, (6) proactive care strategies, and (7) collaborative health professional working and referrals. Addressing service permeability (ease of using services) and local production of candidacy (patient-provider relationships and macro-structural conditions) are understood as most important for addressing avoidable unplanned IBD admissions. The Health System Access Framework is useful for understanding how services need to address patient care.

PURPOSE:Mobility-assistive technology (MAT) faces significant global implementation barriers. This study applied a Consolidated Framework for Implementation Research (CFIR) and Expert Recommendations for Implementing Change (ERIC) matching tools to identify barriers to MAT provision in Saudi Arabia and generate evidence-based implementation strategies. MATERIALS AND METHODS:We triangulated findings from two published studies: a scoping review of barriers to MAT and a mixed-methods study of Saudi Arabian hospitals, including survey data, semi-structured interviews, and policy document analysis. Barriers were identified, mapped to the CFIR constructs, and translated into strategies using the CFIR-ERIC Matching Tool. RESULTS:Triangulation identified 14 distinct barriers across six categories mapped to 14 CFIR constructs within five domains. The CFIR-ERIC tool generated 49 implementation strategies. Planning (n = 17, 35%) and education (n = 13, 26%) were the predominant strategies. Top-ranked strategies included "identify and prepare champions" "conduct educational meetings", and "assess for readiness", demonstrating applicability across multiple barriers. CONCLUSION:The application of implementation science frameworks is a useful way to identify evidence-based strategies to address barriers to MAT provision. The predominance of planning and education strategies, reflecting endorsements from implementation science experts, suggests that systematic preparation and knowledge dissemination are fundamental to improving MAT accessibility. The findings provide actionable guidance for stakeholders in Saudi Arabia and similar settings. Future research should empirically evaluate strategy effectiveness.

PURPOSE:Mobility-related disabilities are the most prevalent disabilities in Saudi Arabia, significantly affecting quality of life. While mobility-assistive technologies (MATs) help mitigate impairments, unmet needs persist with a critical knowledge gap regarding barriers to their provision. This study investigated the barriers to the provision of MAT in the healthcare system of Saudi Arabia. MATERIALS AND METHODS:This mixed methods study combined a cross-sectional survey with a qualitative embedded multiple case study across three public hospitals in two Saudi regions. The survey assessed MAT availability among 67 stakeholders and facilitated recruitment for the qualitative investigation. Semi-structured interviews were conducted with 33 participants (healthcare professionals [HCPs], managers and leaders), and six policy documents were analysed. The Consolidated Framework for Implementation Research (CFIR) guided data collection and analysis. RESULTS:The survey demonstrated that, while basic MATs were generally accessible, advanced devices were not and there were substantial regional disparities. The qualitative analysis identified 52 barriers across all CFIR domains, including dependence on imported devices, high costs and procurement delays, restrictive policies and regulatory ambiguities, insufficient professional healthcare training, inadequate strategic planning and clinical leadership, infrastructural constraints and sociocultural factors that influence patient acceptance. CONCLUSIONS:This study is the first comprehensive investigation of barriers to MAT provision in Saudi Arabia. These findings provide policymakers and practitioners with an evidence-based foundation for designing contextually relevant implementation strategies to enhance equitable MAT provision.

Background In the UK, epilepsy care involves both specialists (for example, neurologists) and generalists (for example, GPs). Policymakers typically consider that epilepsy care should be integrated and involve both specialists and generalists. However, few understand exactly how patients view and compare specialist and generalist care. Aim To explore patient perspectives of specialist care and generalist care for epilepsy in a qualitative evidence synthesis. Design & setting A systematic review of patient perspectives of epilepsy care. A qualitative evidence synthesis was conducted using an identified framework. Method Systematic searches in five databases retrieved 17 eligible studies. Data were extracted and synthesised using framework analysis informed by the ‘United Model of Generalism’. Results The following three themes were developed: ‘Epilepsy care can be burdensome’ (for example, through care fragmentation); ‘Patients' experiences of care is that care is not always accessible’ (for example, lack of a continuum between standardised and interpretive care); and ‘How care could change for people with epilepsy’ (for example, clinicians currently have insufficient time to deviate from protocol-driven care to address psychosocial needs). People with epilepsy frequently observe that generalists lack expertise in epilepsy management. Conclusion This synthesis of patient experiences indicates recommendations should focus on improving communication and integration between specialists and generalists for epilepsy care. Patient experiences indicate specialist care risks being burdensome and generalist knowledge insufficient, requiring enhanced primary care clinician skills and improved awareness of patient psychosocial needs. The findings argue in favour of healthcare policies, materials, and tools to continually support patient perspectives in developing epilepsy services.

Background During the COVID-19 pandemic, 40 mental health and well-being hubs were funded in England to support health and social care staff affected by the pandemic.Aims To describe the characteristics of staff accessing four hubs for support and identify characteristics associated with clinically significant mental health difficulties and work and social functioning.Method Routinely collected screening data were analysed from 1973 individuals across 4 hubs, including mental health, demographic and occupational data and pandemic-related stressors. Factors associated with clinically significant mental health difficulties were identified via logistic regression.Results Most hub clients identified as white women who worked for the UK National Health Service; other groups were less well represented. Hub clients reported high levels of clinically significant mental health difficulties: 60% had severe and often co-occurring difficulties (ie, depression, anxiety, post-traumatic stress disorder or alcohol use) and 80% reported significantly impaired functioning. Younger age, disability status, identifying as from a minority ethnic group, and sexual orientations excluding heterosexual were associated with higher likelihood of having clinically significant mental health difficulties. Suffering financial loss during the pandemic, and prepandemic emotional well-being concerns were the most consistent factors associated with higher difficulties.Conclusions The hubs supported health and social care staff with significant mental health difficulties. Outreach and engagement with under-represented groups should be undertaken to address potential barriers to service access. The findings add to the knowledge base on the support needs of the health and social care workforce and the planning of support in response to future crises.

Abstract Background Inequalities exist in inflammatory bowel disease (IBD) healthcare access, experience and outcomes including in unplanned IBD admissions1. Differing terms are used for unplanned admissions including avoidable, preventable, unnecessary and unwarranted - used interchangeably and without clear definition 2. This study explored the causes, consequences and barriers to mitigating IBD admissions from clinicians’ perspective. Methods A mixed methods study recruited IBD clinicians (gastroenterologists, specialist IBD nurses, surgeons and other allied health professionals) in two inter-related work packages. 1) an international survey developed with IBD clinicians implemented following initial pilot 2) semi-structured qualitative interviews. Clinicians ranked the frequency of types of unplanned admission and contributing factors allocating weighting to a total of 100. Survey results were analysed using descriptive statistics and Friedman and Wilcoxon signed ranked tests. Qualitative interviews were analysed by inductive thematic analysis. Results 145 clinicians started the survey. 66 (45.5%) completed all questions. 80 (55.2%) distinguished between terms, 69 (47.6%) also ranked all admissions. 13 clinicians took part in interviews (11 UK). Preventable admissions were ranked as occurring most often (57.5% ranked first, mean rank 1.62/4) (p <0.001) (Table 1). However, 57 (70%) felt that avoidable and preventable IBD admissions were the same concept. For all unplanned IBD admissions, ranking of reasons were significantly different for all factors (p <0.001) (Table 2). Clinicians ranked unpreventable progression of the disease as most important (mean rank 32.20/100) (p <0.05) followed by missed opportunities for earlier intervention in outpatient care (mean rank 22.39/100) and patient access issues (mean rank 19.52/100). Qualitative findings echoed patient access issues which included lack of timely access to advanced therapies and outpatient care. Health literacy barriers including lack knowledge of how to access services was also identified. Clinicians highlighted under-resourced services and sub-optimal service organisation as prominent issues Conclusion Despite the lack of clarity in existing literature, clinicians mostly feel that avoidable and preventable IBD admissions are the same concept, and consistent terminology should be defined. Whilst clinicians emphasised that unplanned admissions may be necessary, avoidable admissions were also viewed as an important issue. Reasons for unplanned admissions are diverse. IBD services need to consider all of these in order to tackle IBD admissions. References 1-Hawkins RL, Zia M, Hind D, Lobo AJ. Inequalities in Healthcare Access, Experience and Outcomes in Adults With Inflammatory Bowel Disease: A Scoping Review. Inflamm Bowel Dis. Published online April 11, 2024:izae077. doi:10.1093/ibd/izae077 2-Booker M, Purdy S. Towards new definitions of avoidable hospital admissions. Br J Gen Pract. 2022;72(723):464. doi:10.3399/bjgp22X720725

AIM:Controversy exists over whether surgical technique can reduce recurrence following Crohn's resection. This study compares the rate of endoscopic recurrence after different approaches to mesenteric excision (extended/close) and anastomosis (Kono-S/standard of care) in adult patients undergoing ileocolic resection for primary or recurrent Crohn's disease. METHOD:MEErKAT is a UK multicentre, 2 × 2 factorial, randomised, controlled, open-label superiority trial where participants (target sample size = 308) are blinded and centrally randomised (1:1:1:1) to one of four groups: (1) Kono-S + extended mesenteric resection. (2) Kono-S + close mesenteric resection. (3) Standard anastomosis + extended mesenteric resection. (4) Standard anastomosis + close mesenteric resection. The primary outcome is time to endoscopic recurrence of disease (up to 3 years follow-up). Secondary outcomes include rates of severe and symptomatic recurrence, complications, and quality of life scores. The locality of recurrence will be investigated using endoscopic assessment of the mucosa relative to mucosal tattoos placed at the time of operation. The degree and anastomotic locality of different immune cells will be compared before and after each intervention to better understand the mechanistic processes driving disease recurrence. CONCLUSION:This study will robustly evaluate the efficacy of the Kono-S anastomosis technique and extended mesenteric excision in reducing endoscopic recurrence rates. The additive effect of these techniques and local tissue immune response will be investigated. This will provide important evidence to guide the optimal surgical technique and improve our understanding of the processes leading to recurrent disease.

Abstract Key workers are vulnerable to adverse mental health. To ensure service sustainability during COVID-19, Resilience Hubs were established across England offering outreach, screening, and mental health support. This evaluation aimed to describe wider service use, associated costs, and satisfaction among Hub clients (key workers) accessing Hub support. Clients accessing support across four Hubs were invited to complete a service use questionnaire, between 5 and 8 months post referral, collecting satisfaction, wider service use and cost data. Exploratory linear regression assessed the relationship between demographic variables and service use. Most Hub clients reported Hub contact post referral (219/299, 73.2%), with many accessing mental health support (171/299, 57.2%) or on waitlists (34/299, 11.4%). Satisfaction was high, with median helpfulness rated 92 (out of 100), and many stating that Hubs either fully (148/299, 49.5%) or partially (54/299, 18.1%) met their needs. Mental health support accounted for most service use, with higher total service use and costs when including Hub services (£514 versus £213). Key workers have complex needs. Hub services helped clients to access support, with high reported satisfaction indicating that Hubs met clients needs. Further research is required to assess how service use varies according to occupation or demographic characteristics, and whether Hubs are clinically and cost-effective.

BACKGROUND:Protection motivation theory (PMT) shows promise as a basis for motivating healthy behaviours in healthcare settings. There has been no systematic overview of how PMT has been translated into clinical practice and which translation strategies effectively improve outcomes. OBJECTIVES:This scoping review aimed to systematically map and synthesise existing literature on PMT-based interventions targeting health behaviours in healthcare contexts. METHODS:Medline, PsycINFO, and EMBASE were searched for studies applying PMT within healthcare contexts. Eligible populations had a clinical condition. To be eligible, studies had to report a healthcare-delivered PMT intervention with adherence outcomes directly benefiting participants. Two reviewers extracted data on study features, intervention characteristics including behaviour change techniques employed, PMT constructs addressed, results, and research recommendations. Findings were summarised narratively and tabulated. RESULTS:Thirteen studies published between 1998 and 2023 met the eligibility criteria, including 12 randomised trials. Studies addressed acute and chronic conditions across primary, secondary, and non-clinical settings. Half significantly improved behaviour outcomes in intervention groups. All targeted coping-self-efficacy and perceived threat-severity PMT constructs to some degree. Combinations of behaviour change techniques did not clearly differentiate successful outcomes. Studies recommended longer follow-up, clarifying effective PMT component combinations, and drawing on multiple behaviour theories. DISCUSSION:Despite heterogeneity in how PMT interventions were operationalised, they show potential benefits for motivating adherence to healthy behaviours. To enable optimisation and dissemination, consistent nonadherence detection and reporting methods are critical. Further research should include translation of PMT to other healthcare settings, refining methodology and implementing well-powered effectiveness trials in routine care.

BACKGROUND:Good quality primary care is essential for the assessment and treatment of headache but there is evidence that primary care for headache is suboptimal. AIM:To identify the international evidence on the assessment and treatment of headache in adults in primary care. DESIGN & SETTING:A scoping review of the published literature following Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-SCR) guidelines, and a narrative review of the evidence. METHOD:An electronic search of MEDLINE and Embase (1974-2024) was undertaken. Studies meeting the eligibility criteria were included. Results were grouped by study type and were reported narratively. RESULTS:In total, 1125 articles were screened, 43 articles underwent full-text review, and 28 articles were included in the final review. Six studies used comparative methods, of which n = 3/6 investigated educational interventions. The educational interventions found positive effects on learning, and on outcomes such as diagnosis rates, but the only randomised controlled trial (RCT) did not show any benefits of the intervention. Other comparative studies showed satisfaction with GP with an extended role (GPwER) headache services, benefits from direct access to magnetic resonance imaging (MRI), and benefits from a nurse-led headache service. Twenty-two studies used non-comparative methods, such as surveys and interviews, and investigated approaches to assessment, diagnosis, referral rationale, decision making for prescribing prophylactic medications, educational initiatives, direct access to neuroimaging, GPwER, and nurse-led interventions. CONCLUSION:Despite the availability of high quality clinical guidelines on the assessment and management of headache, the evidence shows that its implementation in primary care is problematic and educational interventions are a common focus of published studies. Further research is required to assess the quality of the current evidence and to develop, refine, and deploy interventions that have a signal of efficacy.

Treating idiopathic Early Onset Scoliosis (idiopathic EOS) is challenging due to ongoing growth and extensive follow-ups. While bracing is effective for Adolescent Idiopathic Scoliosis (AIS), its value for children under 10 remains debated. This systematic review and meta-analysis evaluates the effectiveness of spinal bracing in idiopathic EOS, followed to skeletal maturity. We searched Ovid Medline and Web of Science until November 1st, 2023. Studies included idiopathic EOS patients between the ages of 3 and 10 (corresponding to Juvenile Idiopathic Scoliosis), followed to skeletal maturity, with no more than 25

Unplanned hospital admissions are common for people with inflammatory bowel disease (IBD). While clinical predictors of admission are well-documented, research is limited exploring the healthcare delivery factors and system inequalities that contribute to these events. An online survey, distributed via United Kingdom (UK) and European professional networks, and semi-structured interviews explored clinicians’ views of admission types, causes and barriers to preventing admissions. Clinicians ranked causes and barriers to preventing admissions, analysed by descriptive statistics and Friedman and Wilcoxon rank tests. We used framework analysis, guided by Candidacy Theory, to analyse qualitative data across data types to explore issues of healthcare access. 80 clinicians completed the survey, 13 were interviewed. For all unplanned IBD admissions, an unpreventable disease progression was ranked the highest cause (mean rank [MR] 32.20/100) ( p <0.05), followed by missed opportunities for earlier intervention (MR 22.39/100) and patient access issues (MR 19.52/100). Qualitative interviews elaborated on avoidable unplanned admissions through: (1) Missed opportunities in outpatient or primary care, (2) critical delays in specialised care, and (3) system constraints blocking timely action. Key challenges in preventing admissions across the study related to patient navigation of services, organisational barriers, provider decision-making and structural issues that impede access to care. Most avoidable admissions were perceived not as a failure of individuals, but a reflection of broader service inefficiencies and inequities. Reducing IBD admissions requires systemic investment and improvements in care navigation, rapid-access pathways, professional decision-making, patient education and service integration. ⍰ Unplanned hospital admissions are a common and costly outcome for people living with inflammatory bowel disease (IBD). ⍰ While clinical predictors of admission are well-documented, there is limited research exploring the healthcare delivery factors and system inequalities that contribute to these events. ⍰ This study presents a clinician-led definition of avoidable IBD admissions as those resulting from missed outpatient opportunities, specialist delays, and system constraints. ⍰ While disease progression was the perceived primary cause, IBD admissions are also perceived to be driven by modifiable systemic failures, specifically waiting times, resource gaps, and navigation hurdles influenced by social determinants. ⍰ The findings advocate for and inform prospective service development interventions for improved rapid-access flare pathways and the strengthening of patient education to improve service navigation. ⍰ There is a clear need for significant investment in workforce and infrastructure, specifically regarding infusion capacity and specialist staffing, to prevent missed care escalation.

BACKGROUND:Relational continuity of care (patients seeing the same GP) is associated with better outcomes for patients, but it has been declining in general practice in the UK. AIM:To understand what interventions have been tried to improve relational continuity of care in general practice in the UK. DESIGN & SETTING:Scoping review of articles on UK General Practice and written in English. METHOD:An electronic search of MEDLINE, Embase, and Scopus from 2002 to the present day was undertaken. Sources of grey literature were also searched. Studies that detailed service-level methods of achieving relational continuity of care with a GP in the UK were eligible for inclusion. Interventions were described narratively in relation to the elements listed in the Template for Intervention Description and Replication (TIDieR). A logic model describing the rationale behind interventions was constructed. RESULTS:Seventeen unique interventions were identified. The interventions used a wide variety of strategies to try to improve relational continuity. This included personal lists, amended booking processes, regular reviews, digital technology, facilitated follow-ups, altered appointment times, and use of acute hubs. Twelve of the interventions targeted specific patient groups for increased continuity while others focused on increasing continuity for all patients. Changes in continuity levels were measured inconsistently using several different methods. CONCLUSION:Several different strategies have been used in UK general practices in an attempt to improve relational continuity of care. While there is a similar underlying logic to these interventions, their scope, aims, and methods vary considerably. Furthermore, owing to a weak evidence base, comparing their efficacy remains challenging.

Background Without surgical repair, flexor tendon injuries do not heal and patients’ ability to bend fingers and grip objects is impaired. However, flexor tendon repair surgery also requires optimal rehabilitation. There are currently three custom-made splints used in the rehabilitation of zone I/II flexor tendon repairs, each with different assumed harm/benefit profiles: the dorsal forearm and hand-based splint (long), the Manchester short splint (short), and the relative motion flexion splint (mini). There is, however, no robust evidence as to which splint, if any, is most clinical or cost effective. The Flexor Injury Rehabilitation Splint Trial (FIRST) was designed to address this evidence gap. Methods FIRST is a parallel group, superiority, analyst-blind, multi-centre, individual participant-randomised controlled trial. Participants will be assigned 1:1:1 to receive either the long, short, or mini splint. We aim to recruit 429 participants undergoing rehabilitation following zone I/II flexor tendon repair surgery. Potential participants will initially be identified prior to surgery, in NHS hand clinics across the UK, and consented and randomised at their splint fitting appointment post-surgery. The primary outcome will be the mean post-randomisation score on the patient-reported wrist and hand evaluation measure (PRWHE), assessed at 6, 12, 26, and 52 weeks post randomisation. Secondary outcome measures include blinded grip strength and active range of movement (AROM) assessments, adverse events, adherence to the splinting protocol (measured via temperature sensors inserted into the splints), quality of life assessment, and further patient-reported outcomes. An economic evaluation will assess the cost-effectiveness of each splint, and a qualitative sub-study will evaluate participants’ preferences for, and experiences of wearing, the splints. Furthermore, a mediation analysis will determine the relationship between patient preferences, splint adherence, and splint effectiveness. Discussion FIRST will compare the three splints with respect to clinical efficacy, complications, quality of life and cost-effectiveness. FIRST is a pragmatic trial which will recruit from 26 NHS sites to allow findings to be generalisable to current clinical practice in the UK. It will also provide significant insights into patient experiences of splint wear and how adherence to splinting may impact outcomes. Trial registration ISRCTN: 10236011

AIM:Faecal immunochemical testing (FIT) is used to triage people with signs or symptoms of a colorectal cancer (CRC). Recent guidelines have recommended further research to improve access, uptake and return of FIT. This systematic scoping review aims to understand the barriers and facilitators to FIT testing in symptomatic patients. METHOD:Qualitative, quantitative and mixed-methods studies published after September 2013 were included. MEDLINE, EMBASE and PsycINFO databases were searched to identify publications examining barriers and facilitators to FIT. Initially, the data underwent thematic analysis, and subsequently, factors were aligned to components of the Capability, Opportunity, Motivation, Behaviour model. All outcomes are presented in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS:One thousand two hundred thirty-two papers were identified; 11 met the inclusion criteria. Barriers and facilitators were identified at the patient (e.g., knowledge), provider (e.g., general practitioner awareness) and service level (e.g., method of providing FIT kits). Factors were categorised into the subcomponents of the model: psychological capability (e.g., lack of FIT knowledge), reflective motivation (e.g., beliefs regarding FIT sampling and faeces being unhygienic) and automatic motivation (e.g., embarrassment, scary, anxiety provoking). Gaps in knowledge emerged in three domains: (1) patient experience, (2) FIT pathway and (3) healthcare professionals experience of FIT. CONCLUSION:This systematic scoping review provides a summary of the literature on FIT uptake, and identified factors across multiple levels and components. To increase adherence to FIT completion within primary care, a multifaceted theory and evidence-based approach is needed to underpin future behavioural science interventions.

Background A previous controlled trial of autologous haematopoietic stem -cell transplantation (HSCT) in patients with refractory Crohn's disease did not meet its primary endpoint and reported high toxicity. We aimed to assess the safety and efficacy of HSCT with an immune -ablative regimen of reduced intensity versus standard of care in this patient population. Methods This open -label, multicentre, randomised controlled trial was conducted in nine National Health Service hospital trusts across the UK. Adults (aged 18-60 years) with active Crohn's disease on endoscopy (Simplified Endoscopic Score for Crohn's Disease [SES-CD] ulcer sub -score of >= 2) refractory to two or more classes of biological therapy, with no perianal or intra-abdominal sepsis or clinically significant comorbidity, were recruited. Participants were centrally randomly assigned (2:1) to either HSCT with a reduced dose of cyclophosphamide (intervention group) or standard care (control group). Randomisation was stratified by trial site by use of random permuted blocks of size 3 and 6. Patients in the intervention group underwent stem -cell mobilisation (cyclophosphamide 1 g/m2 with granulocyte colony -stimulating factor (G-CSF) 5 mu g/kg) and stem -cell harvest (minimum 2 center dot 0 x 106 CD34+ cells per kg), before conditioning (fludarabine 125 mg/m2, cyclophosphamide 120 mg/kg, and rabbit anti-thymocyte globulin [thymoglobulin] 7 center dot 5 mg/kg in total) and subsequent stem -cell reinfusion supported by G-CSF. Patients in the control group continued any available conventional, biological, or nutritional therapy. The primary outcome was absence of endoscopic ulceration (SES-CD ulcer sub -score of 0) without surgery or death at week 48, analysed in the intention -totreat population by central reading. This trial is registered with the ISRCTN registry, 17160440. Findings Between Oct 18, 2018, and Nov 8, 2019, 49 patients were screened for eligibility, of whom 23 (47%) were randomly assigned: 13 (57%) to the intervention group and ten (43%) to the control group. In the intervention group, ten (77%) participants underwent HSCT and nine (69%) reached 48 -week follow-up; in the control group, nine (90%) reached 48 -week follow-up. The trial was halted in response to nine reported suspected unexpected serious adverse reactions in six (46%) patients in the intervention group, including renal failure due to proven thrombotic microangiopathy in three participants and one death due to pulmonary veno-occlusive disease. At week 48, absence of endoscopic ulceration without surgery or death was reported in three (43%) of seven participants in the intervention group and in none of six participants in the control group with available data. Serious adverse events were more frequent in the intervention group (38 in 13 [100%] patients) than in the control group (16 in four [40%] patients). A second patient in the intervention group died after week 48 of respiratory and renal failure. Interpretation Although HSCT with an immune -ablative regimen of reduced intensity decreased endoscopic disease activity, significant adverse events deem this regimen unsuitable for future clinical use in patients with refractory Crohn's disease.

Background Over 55,000 spinal operations are performed annually in the NHS. Effective postoperative analgesia facilitates early mobilisation and assists rehabilitation and hospital discharge, but is difficult to achieve with conventional, opioid-based, oral analgesia. The clinical and cost-effectiveness of two alternative techniques, namely intrathecal opioid and the more novel erector-spinae plane blockade, is unknown. The Pain Relief After Instrumented Spinal Surgery (PRAISE) trial aims to evaluate these techniques. Methods PRAISE is a multicentre, prospective, parallel group, patient-blinded, randomised trial, seeking to recruit 456 adult participants undergoing elective, posterior lumbar-instrumented spinal surgery from up to 25 NHS hospitals. Participants will be randomised 1:1:1 to receive (1) Usual Care with local wound infiltration, (2) Intrathecal Opioid plus Usual Care with local wound infiltration or (3) Erector Spinae Plane blockade plus Usual Care with no local wound infiltration. The primary outcome is pain on movement on a 100mm visual analogue scale at 24 hours post-surgery. Secondary outcomes include pain at rest, leg pain, quality of recovery (QoR-15), postoperative opioid consumption, time to mobilisation, length of hospital stay, health utility (EQ-5D-5L), adverse events and resource use. Parallel economic evaluation will estimate incremental cost-effectiveness ratios. Results Differences in the primary outcome at 24 hours will be estimated by mixed-effects linear regression modelling, with fixed effects for randomisation factors and other important prognostic variables, and random effects for centre, using the as-randomised population. Treatment effects with 95% confidence intervals will be presented. Conclusion The study is due to open in May 2024 and complete in 2026. Conflicts of Interest No conflicts of interest declared Sources of Funding NIHR Health Technology Award – grant number NIHR153170 Trial presentations so far APOMP 2023 and 2024; RCOA conference, York, November 2023; Faculty of Pain Management training day, London, February 2024.