Going beyond randomised controlled trials to assess treatment effect heterogeneity across target populations.

Methods have been developed for transporting evidence from randomised controlled trials (RCTs) to target populations. However, these approaches allow only for differences in characteristics observed in the RCT and real-world data (overt heterogeneity). These approaches do not recognise heterogeneity of treatment effects (HTE) according to unmeasured characteristics (essential heterogeneity). We use a target trial design and apply a local instrumental variable (LIV) approach to electronic health records from the Clinical Practice Research Datalink, and examine both forms of heterogeneity in assessing the comparative effectiveness of two second-line treatments for type 2 diabetes mellitus. We first estimate individualised estimates of HTE across the entire target population defined by applying eligibility criteria from national guidelines (n = 13,240) within an overall target trial framework. We define a subpopulation who meet a published RCT's eligibility criteria ('RCT-eligible', n = 6497), and a subpopulation who do not ('RCT-ineligible', n = 6743). We compare average treatment effects for pre-specified subgroups within the RCT-eligible subpopulation, the RCT-ineligible subpopulation, and within the overall target population. We find differences across these subpopulations in the magnitude of subgroup-level treatment effects, but that the direction of estimated effects is stable. Our results highlight that LIV methods can provide useful evidence about treatment effect heterogeneity including for those subpopulations excluded from RCTs.

Exploring cost-effectiveness heterogeneity of high flow nasal cannula (HFNC) therapy in acutely ill children - Insights from step-up FIRST-ABC trial using a machine learning method.

OBJECTIVES: To investigate heterogeneity in the cost-effectiveness of high flow nasal cannula (HFNC) therapy compared to continuous positive airway pressure (CPAP) for acutely ill children requiring noninvasive respiratory support. METHODS: Using data from the FIRST-line support for Assistance in Breathing in Children (FIRST-ABC) trial, we explore heterogeneity at the patient and subgroup levels using two causal forest approaches and a seemingly unrelated regression (SUR) approach for comparison. FIRST-ABC is a non-inferiority randomized controlled trial (ISRCTN60048867) involving 24 UK paediatric intensive care units. The 'step-up' trial focuses on acutely ill children aged 0 to 15 years, requiring non-invasive respiratory support. A total of 600 children were randomly assigned to HFNC and CPAP groups in a 1:1 allocation ratio, with 94 patients excluded due to data unavailability. RESULTS: The primary outcome is the incremental net monetary benefit (INB) of HFNC compared to CPAP, using a willingness-to-pay threshold of £20,000 per QALY gain. INB is derived from total costs and Quality Adjusted Life Years (QALYs) at six months. Subgroup analysis showed that some subgroups such as male children, those aged less than 12 months, and those without severe respiratory distress at randomization had more favorable INB results. Patient-level analysis revealed heterogeneity in INB estimates, particularly driven by the cost component, with greater uncertainty for those with higher INBs. CONCLUSIONS: The estimated overall INB of HFNC is significantly larger for specific patient subgroups, suggesting that the cost-effectiveness of HFNC can be heterogeneous which highlight the importance of considering patient characteristics in evaluating the cost-effectiveness of HFNC.

How I Do It: Process Control in Medical Student Experiences of Surgery.

OBJECTIVE: Extreme variation exists in teaching and clinical exposure for medical students, both from specialty-to-specialty but also between universities. There is mounting literature highlighting the need to reform and standardize surgical education to allow for unified graduate competency. In line with the recommendations from the GMC and the Royal College of Surgeons England (RCSEng), Queens University Belfast (QUB) significantly revised their undergraduate medical programme. Within this new curriculum is the introduction of Specialty Focus week in Surgery. This report reviews the processes used in the introduction of this week. DESIGN: The initial week was formulated with a weekly timetable consisting of tutorials, bedside teaching and students following a peri-operative case. Run charts were populated with an alert when feedback dropped below a certain standard, which then triggered an intervention. PARTICIPANTS: Feedback was collected via a QR code from the first 200 surgical student. SETTINGS: Belfast City Hospital in association with QUB undergraduate curriculum. RESULTS: Run charts resulted in an alert when feedback dropped below 8/10. Following this we implemented smaller group bedside teaching. There was a significant improvement in feedback post intervention (p = 0.04) with no further alerts. Overall feedback had a nonsignificant feedback improvement post intervention (p = 0.07) with once again, no further alerts. CONCLUSION: This review has shown how we have provided some standardization of local surgical teaching, as well as having a process centered model of monitoring. This approach is easy to implement and could be reproduced elsewhere.

Why did England change its law on deceased organ donation in 2019? The dynamic interplay between evidence and values.

In the three years since the law on adult deceased organ donation consent in England changed to include an opt-out system, there has been no discernible change to donation rates. The lack of a positive impact on donation rates was predicted by many of those who took part in debates before and during the passage of the Bill through Parliament. This invites the question as to why England moved to an opt-out system for organ donation despite equivocal evidence of likely benefit and opposition from expert health professional organisations. To address this question qualitative analyses of Parliamentary debates on organ donation was undertaken. This revealed a shift from a dominant position, which gave primacy to the evidence of likely effects, towards a more normative position where a deemed consent option was viewed as the 'correct thing to do' and the limited and conflicting evidence viewed in a positive light. By 2017, following Wales's move to an opt-out system, together with continued lobbying for similar changes for England by professional and patient groups, alongside sustained public popularity for organ donation, the balance of opinion had shifted towards a system where deemed consent would become the default position for most English adults.

Validation of arteriovenous access stage (AVAS) classification: a prospective, international multicentre study.

Background: The arteriovenous access stage (AVAS) classification provides evaluation of upper extremity vessels for vascular access (VA) suitability. It divides patients into classes within three main groups: suitable for native fistula (AVAS1) or prosthetic graft (AVAS2), and patients not suitable for conventional native or prosthetic VA (AVAS3). We validated this system on a prospective dataset. Methods: A prospective, international observational study (NCT04796558) involved 11 centres from 8 countries. Patient recruitment was from March 2021 to January 2024. Demographic data, risk factors, vessels parameters, VA types, AVAS class and early VA failure were collected. Percentage agreement was used to assess predictive ability of AVAS (comparison of AVAS and created VA) and consistency of AVAS assessment between evaluators. Pearson's Chi-squared test was used for comparison of early failure rate of conventional (predicted by AVAS) and unconventional (not predicted by AVAS) VA. Results: From 1034 enrolled patients, 935 had arteriovenous fistula or graft, 99 patients did not undergo VA creation due opting for alternative renal replacement therapies, experiencing health complications, death or non-compliance. AVAS1 had 91.2%, AVAS2 7.2% and AVAS3 1.6% of patients. Agreement between evaluators was 89%. The most frequently created VAs were radial-cephalic (46%) and brachial-cephalic (27%) fistulae. The accuracy of AVAS versus created access was 79%. In comparison, VA predicted by clinicians versus created access was 62.1%. Inaccuracy of AVAS prediction was more common with higher AVAS classes, and the most common reason for inaccuracy was creation of distal VA despite less favourable anatomy (17%). Patients with unconventional VA had higher early failure rate than patients with conventional VA (20% vs 9.3%, respectively, P = .002). Conclusion: AVAS is effective in predicting VA creation, but overall accuracy is reduced at higher AVAS classes when the complexity of decision-making increases and proximal vessels require preservation. When AVAS was followed by clinicians, early failure was significantly decreased.

Highly stretchable dynamic hydrogels for soft multilayer electronics.

Recent progress in the development of synthetic polymer networks has enabled the next generation of hydrogel-based machines and devices. The ability to mimic the mechanical and electrical properties of human tissue gives great potential toward the fields of bioelectronics and soft robotics. However, fabricating hydrogel devices that display high ionic conductivity while maintaining high stretchability and softness remains unmet. Here, we synthesize supramolecular poly(ionic) networks, which display high stretchability (>1500%), compressibility (>90%), and rapid self-recovery (<30 s), while achieving ionic conductivities of up to 0.1 S cm -1. Dynamic cross-links give rise to inter-layer adhesion and a stable interface is formed on account of ultrahigh binding affinities (>1013 M-2). Superior adherence between layers enabled the fabrication of an intrinsically stretchable hydrogel power source, paving the way for the next generation of multi-layer tissue mimetic devices.

Trends in organ donation in England, Scotland and Wales in the context of the COVID-19 pandemic and 'opt-out' legislation.

BACKGROUND: In May 2020, England implemented soft 'opt-out' or 'deemed consent' for deceased donation with the intention of raising consent rates. However, this coincided with the COVID-19 pandemic, making it difficult to assess the early impact of the law change. Wales and Scotland changed their organ donation legislation to implement soft opt-out systems in 2015 and 2021 respectively. This study provides a descriptive analysis of changes in consent and transplant rates for deceased organ donation in England, Scotland and Wales. METHODS: Logistic regression and descriptive trend analysis were employed to assess the probability of a patient who died in critical care becoming a donor, and to report consent rates using data, respectively, from the Intensive Care National Audit and Research Centre (ICNARC) in England from 1 April 2014 to 30 September 2021, and from the Potential Donor Audit for England, Scotland and Wales from April 2010 to June 2023. RESULTS: The number of eligible donors in April-June 2020 were 56.5%, 59.3% and 57.6% lower in England, Scotland and Wales relative to April-June 2019 (pre-pandemic). By April-June 2023, the number of eligible donors had recovered to 87.4%, 64.2% and 110.3%, respectively, of their levels in 2019. The consent rate in England, Scotland and Wales reduced from 68.3%, 63.0% and 63.6% in April-June 2019 to 63.2%, 60.5% and 56.3% in April-June 2023. CONCLUSIONS: While the UK organ donation system shows signs of recovery from the COVID-19 pandemic, the number of eligible potential donors and consent rates remain below their pre-pandemic levels.

Are there patients with an intracapsular fracture of the hip who may benefit from an uncemented hemiarthroplasty?

Aims: Cemented hemiarthroplasty is an effective form of treatment for most patients with an intracapsular fracture of the hip. However, it remains unclear whether there are subgroups of patients who may benefit from the alternative operation of a modern uncemented hemiarthroplasty - the aim of this study was to investigate this issue. Knowledge about the heterogeneity of treatment effects is important for surgeons in order to target operations towards specific subgroups who would benefit the most. Methods: We used causal forest analysis to compare subgroup- and individual-level treatment effects between cemented and modern uncemented hemiarthroplasty in patients aged > 60 years with an intracapsular fracture of the hip, using data from the World Hip Trauma Evaluation 5 (WHiTE 5) multicentre randomized clinical trial. EuroQol five-dimension index scores were used to measure health-related quality of life at one, four, and 12 months postoperatively. Results: Our analysis revealed a complex landscape of responses to the use of a cemented hemiarthroplasty in the 12 months after surgery. There was heterogeneity of effects with regard to baseline characteristics, including age, pre-injury health status, and lifestyle factors such as alcohol consumption. This heterogeneity was greater at the one-month mark than at subsequent follow-up timepoints, with particular regard to subgroups based on age. However, for all subgroups, the effect estimates for quality of life lay within the confidence intervals derived from the analysis of all patients. Conclusion: The use of a cemented hemiarthroplasty is expected to increase health-related quality of life compared with modern uncemented hemiarthroplasty for all subgroups of patients aged > 60 years with a displaced intracapsular fracture of the hip.

Exploring Heterogeneity in Cost-Effectiveness Using Machine Learning Methods: A Case Study Using the FIRST-ABC Trial.

OBJECTIVE: The aim of this study was to explore heterogeneity in the cost-effectiveness of high-flow nasal cannula (HFNC) therapy compared with continuous positive airway pressure (CPAP) in children following extubation. DESIGN: Using data from the FIRST-line support for Assistance in Breathing in Children (FIRST-ABC) trial, we explore heterogeneity at the individual and subgroup levels using a causal forest approach, alongside a seemingly unrelated regression (SUR) approach for comparison. SETTINGS: FIRST-ABC is a noninferiority randomized controlled trial (ISRCTN60048867) including children in UK paediatric intensive care units, which compared HFNC with CPAP as the first-line mode of noninvasive respiratory support. PATIENTS: In the step-down FIRST-ABC, 600 children clinically assessed to require noninvasive respiratory support were randomly assigned to HFNC and CPAP groups with 1:1 treatment allocation ratio. In this analysis, 118 patients were excluded because they did not consent to accessing their medical records, did not consent to follow-up questionnaire or did not receive respiratory support. MEASUREMENTS AND MAIN RESULTS: The primary outcome of this study is the incremental net monetary benefit (INB) of HFNC compared with CPAP using a willingness-to-pay threshold of £20,000 per QALY gain. INB is calculated based on total costs and quality adjusted life years (QALYs) at 6 months. The findings suggest modest heterogeneity in cost-effectiveness of HFNC compared with CPAP at the subgroup level, while greater heterogeneity is detected at the individual level. CONCLUSIONS: The estimated overall INB of HFNC is smaller than the INB for patients with better baseline status suggesting that HFNC can be more cost-effective among less severely ill patients.

Persistence and heterogeneity of the effects of educating mothers to improve child immunisation uptake: Experimental evidence from Uttar Pradesh in India.

Childhood vaccinations are among the most cost-effective health interventions. Yet, in India, where immunisation services are widely available free of charge, a substantial proportion of children remain unvaccinated. We revisit households 30 months after a randomised experiment of a health information intervention designed to educate mothers on the benefits of child vaccination in Uttar Pradesh, India. We find that the large short-term effects on the uptake of diphtheria-pertussis-tetanus and measles vaccination were sustained at 30 months, suggesting the intervention did not simply bring forward vaccinations. We apply causal forests and find that the intervention increased vaccination uptake, but that there was substantial variation in the magnitude of the estimated effects. We conclude that characterising those who benefited most and conversely those who benefited least provides policy-makers with insights on how the intervention worked, and how the targeting of households could be improved.

Comparative effectiveness of second line oral antidiabetic treatments among people with type 2 diabetes mellitus: emulation of a target trial using routinely collected health data.

OBJECTIVE: To compare the effectiveness of three commonly prescribed oral antidiabetic drugs added to metformin for people with type 2 diabetes mellitus requiring second line treatment in routine clinical practice. DESIGN: Cohort study emulating a comparative effectiveness trial (target trial). SETTING: Linked primary care, hospital, and death data in England, 2015-21. PARTICIPANTS: 75 739 adults with type 2 diabetes mellitus who initiated second line oral antidiabetic treatment with a sulfonylurea, DPP-4 inhibitor, or SGLT-2 inhibitor added to metformin. MAIN OUTCOME MEASURES: Primary outcome was absolute change in glycated haemoglobin A1c (HbA1c) between baseline and one year follow-up. Secondary outcomes were change in body mass index (BMI), systolic blood pressure, and estimated glomerular filtration rate (eGFR) at one year and two years, change in HbA1c at two years, and time to ≥40% decline in eGFR, major adverse kidney event, hospital admission for heart failure, major adverse cardiovascular event (MACE), and all cause mortality. Instrumental variable analysis was used to reduce the risk of confounding due to unobserved baseline measures. RESULTS: 75 739 people initiated second line oral antidiabetic treatment with sulfonylureas (n=25 693, 33.9%), DPP-4 inhibitors (n=34 464 ,45.5%), or SGLT-2 inhibitors (n=15 582, 20.6%). SGLT-2 inhibitors were more effective than DPP-4 inhibitors or sulfonylureas in reducing mean HbA1c values between baseline and one year. After the instrumental variable analysis, the mean differences in HbA1c change between baseline and one year were -2.5 mmol/mol (95% confidence interval (CI) -3.7 to -1.3) for SGLT-2 inhibitors versus sulfonylureas and -3.2 mmol/mol (-4.6 to -1.8) for SGLT-2 inhibitors versus DPP-4 inhibitors. SGLT-2 inhibitors were more effective than sulfonylureas or DPP-4 inhibitors in reducing BMI and systolic blood pressure. For some secondary endpoints, evidence for SGLT-2 inhibitors being more effective was lacking-the hazard ratio for MACE, for example, was 0.99 (95% CI 0.61 to 1.62) versus sulfonylureas and 0.91 (0.51 to 1.63) versus DPP-4 inhibitors. SGLT-2 inhibitors had reduced hazards of hospital admission for heart failure compared with DPP-4 inhibitors (0.32, 0.12 to 0.90) and sulfonylureas (0.46, 0.20 to 1.05). The hazard ratio for a ≥40% decline in eGFR indicated a protective effect versus sulfonylureas (0.42, 0.22 to 0.82), with high uncertainty in the estimated hazard ratio versus DPP-4 inhibitors (0.64, 0.29 to 1.43). CONCLUSIONS: This emulation study of a target trial found that SGLT-2 inhibitors were more effective than sulfonylureas or DPP-4 inhibitors in lowering mean HbA1c, BMI, and systolic blood pressure and in reducing the hazards of hospital admission for heart failure (v DPP-4 inhibitors) and kidney disease progression (v sulfonylureas), with no evidence of differences in other clinical endpoints.

The association of comorbid dementia with length of stay, cost and mortality among older adults in US acute hospitals: An observational study.

BACKGROUND: Although overall health and social care expenditures among persons with dementia are larger than for other diseases, the resource and cost implications of a comorbid diagnosis of dementia in acute hospitals in the U.S. are largely unknown. We estimate the difference in inpatient outcomes between similar hospital admissions for patients with and without comorbid dementia (CD). METHODS: Inpatient admissions, from the U.S. National Inpatient Sample (2016-2019), were stratified according to hospital characteristics and primary diagnosis (using ICD-10-CM codes), and entropy balanced within strata according to patient and hospital characteristics to create two comparable groups of admissions for patients (aged 65 years or older) with and without CD (a non-primary diagnosis of dementia). Generalized linear regression modeling was then used to estimate differences in length of stay (LOS), cost, absolute mortality risk and number of procedures between these two groups. RESULTS: The final sample consisted of 8,776,417 admissions, comprised of 1,013,879 admissions with and 7,762,538 without CD. CD was associated with on average 0.25 (95 % CI: 0.24-0.25) days longer LOS, 0.4 percentage points (CI: 0.37-0.42) higher absolute mortality risk, $1187 (CI: -1202 to -1171) lower inpatient costs and 0.21 (CI: -0.214 to -0.210) fewer procedures compared to similar patients without CD. CONCLUSION: Comorbid dementia is associated with longer LOS and higher mortality in acute hospitals but lower inpatient costs and fewer procedures. This highlights potential communication issues between dementia patients and hospital staff, with patients struggling to express their needs and staff lacking sufficient dementia training to address communication challenges.

A systematic review of national interventions and policies to optimize antibiotic use in healthcare settings in England.

OBJECTIVES: To identify and assess the effectiveness of national antibiotic optimization interventions in primary and secondary care in England (2013-2022). METHODS: A systematic scoping review was conducted. Literature databases (Embase and Medline) were used to identify interventions and evaluations. Reports included the UK AMR Strategy (2013-2018), National Action Plan (2019-2024) and English Surveillance Programme for Antimicrobial Utilisation and Resistance (ESPAUR) reports (2014-2022). The design, focus and quality of evaluations and the interventions' effectiveness were extracted. FINDINGS: Four hundred and seventy-seven peer-reviewed studies and 13 reports were screened. One hundred and three studies were included for review, identifying 109 interventions in eight categories: policy and commissioning (n = 9); classifications (n = 1); guidance and toolkits (n = 22); monitoring and feedback (n = 17); professional engagement and training (n = 19); prescriber tools (n = 12); public awareness (n = 17); workforce and governance (n = 12).Most interventions lack high-quality effectiveness evidence. Evaluations mainly focused on clinical, microbiological or antibiotic use outcomes, or intervention implementation, often assessing how interventions were perceived to affect behaviour. Only 16 interventions had studies that quantified effects on prescribing, of which six reported reductions. The largest reduction was reported with structural-level interventions and attributed to a policy and commissioning intervention (primary care financial incentives). Behavioural interventions (guidance and toolkits) reported the greatest impact in hospitals. CONCLUSIONS: Many interventions have targeted antibiotic use, each pulling different levers across the health system simultaneously. On the basis of these studies, structural-level interventions may have the greatest impact. Collectively, the combination of interventions may explain England's decline in prescribing but direct evidence of causality is unavailable.

Rate and reasons for peritoneal dialysis dropout following haemodialysis to peritoneal dialysis switch: a systematic review and meta-analysis.

BACKGROUND: Patient experiences and survival outcomes can be influenced by the circumstances related to dialysis initiation and subsequent modality choices. This systematic review and meta-analysis aimed to explore the rate and reasons for peritoneal dialysis (PD) dropout following haemodialysis (HD) to PD switch. METHOD: This systematic review conducted searches in four databases, including Medline, PubMed, Embase, and Cochrane. The protocol was registered on PROSPERO (study ID: CRD42023405718). Outcomes included factors leading to the switch from HD to PD, the rate and reasons for PD dropout and mortality difference in two groups (PD first group versus HD to PD group). The Critical Appraisal Skills Programme (CASP) checklist and the GRADE tool were used to assess quality. RESULTS: 4971 papers were detected, and 13 studies were included. On meta-analysis, there was no statistically significant difference in PD dropout in the PD first group (OR: 0.81; 95%CI: 0.61, 1.09; I2 = 83%; P = 0.16), however, there was a statistically significant reduction in the rate of mortality (OR: 0.48; 95%CI: 0.25, 0.92; I2 = 73%; P = 0.03) compared to the HD to PD group. The primary reasons for HD to PD switch, included vascular access failure, patient preference, social issues, and cardiovascular disease. Causes for PD dropout differed between the two groups, but inadequate dialysis and peritonitis were the main reasons for PD dropout in both groups. CONCLUSION: Compared to the PD first group, a previous HD history may not impact PD dropout rates for patients, but it could impact mortality in the HD to PD group. The reasons for PD dropout differed between the two groups, with no statistical differences. Psychosocial reasons for PD dropout are valuable to further research. Additionally, establishing a consensus on the definition of PD dropout is crucial for future studies.

Heterogeneity within the Oregon Health Insurance Experiment: An application of causal forests.

Existing evidence regarding the effects of Medicaid expansion, largely focused on aggregate effects, suggests health insurance impacts some health, healthcare utilization, and financial hardship outcomes. In this study we apply causal forest and instrumental forest methods to data from the Oregon Health Insurance Experiment (OHIE), to explore heterogeneity in the uptake of health insurance, and in the effects of (a) lottery selection and (b) health insurance on a range of health-related outcomes. The findings of this study suggest that the impact of winning the lottery on the health insurance uptake varies among different subgroups based on age and race. In addition, the results generally coincide with findings in the literature regarding the overall effects: lottery selection (and insurance) reduces out-of-pocket spending, increases physician visits and drug prescriptions, with little (short-term) impact on the number of emergency department visits and hospital admissions. Despite this, we detect quite weak evidence of heterogeneity in the effects of the lottery and of health insurance across the outcomes considered.

The British Transplantation Society guidelines on ethics, law and consent in relation to deceased donors after circulatory death.

The British Transplantation Society (BTS) 'Guideline on transplantation from deceased donors after circulatory death' has recently been updated and this manuscript summarises the relevant recommendations from chapters specifically related to law, ethics, donor consent and informing the recipient.

British Transplantation Society guidelines on abdominal organ transplantation from deceased donors after circulatory death.

The British Transplantation Society (BTS) 'Guideline on transplantation from deceased donors after circulatory death' has recently been updated and this manuscript summarises the relevant recommendations in abdominal organ transplantation from Donation after Circulatory Death (DCD) donors, encompassing the chapters on liver, kidney, pancreas and islet cell transplantation.

Implementing mental health support teams in schools and colleges: the perspectives of programme implementers and service providers.

Background: Between 2018 and 2025, a national implementation programme is funding more than 500 new mental health support teams (MHSTs) in England, to work in education settings to deliver evidence-based interventions to children with mild to moderate mental health problems and support emotional wellbeing for all pupils. A new role, education mental health practitioner (EMHP), has been created for the programme.Aims: A national evaluation explored the development, implementation and early progress of 58 MHSTs in the programme's first 25 'Trailblazer' sites. This paper reports the views and experiences of people involved in MHST design, implementation and service delivery at a local, regional and national level.Methods: Data are reported from in-depth interviews with staff in five Trailblazer sites (n = 71), and the programme's regional (n = 52) and national leads (n = 21).Results: Interviewees universally welcomed the creation of MHSTs, but there was a lack of clarity about their purpose, concerns that the standardised CBT interventions being offered were not working well for some children, and challenges retaining EMHPs.Conclusions: This study raises questions about MHSTs' service scope, what role they should play in addressing remaining gaps in mental health provision, and how EMHPs can develop the skills to work effectively with diverse groups.

When There is No Guidance From the Guidelines: Renal Transplantation in Recipients With Class III Obesity.

Whilst renal transplantation is the optimal treatment for many patients with end-stage kidney disease, the latest international guidelines are unable to make recommendations for the management of patients with end-stage kidney stage kidney disease and Class III Obesity (BMI ≥40 kg/m2). Data on all adult patients receiving a kidney-only-transplant in the UK between 2015-2021 were analysed from a prospectively collected database and interrogated across a range of parameters. We then analysed in detail the outcomes of patients transplanted at the highest-volume unit. There were 22,845 renal transplants in the study time-period; just 44 (0.2%) were performed in recipients with a BMI ≥40 kg/m2. Most transplant centres did not transplant any patients in this category. In the centre with the highest volume, there were 21 transplants (9 living donor) performed in 20 individuals (13 male, median age 46 years). One-year patient and death-censored graft survival was 95% and 85%. Successful transplantation is possible in patients with BMI ≥40 kg/m2 but carries additional risk. Obesity should not be the sole factor considered when deciding on transplant suitability. Restricting transplantation to a small number of high-volume centres in each country should be considered to optimize outcomes.