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.

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.

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.

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.

Management of an aneurysmal arteriovenous fistula in kidney transplant recipients.

Aneurysms remain the most common complication of an arteriovenous fistula created for dialysis access. The management of an aneurysmal arteriovenous fistula (AAVF) in kidney transplant recipients remains contentious with a lack of clear clinical guidelines. Recipients of a functioning graft do not require the fistula for dialysis access, however risk of graft failure and needing the access at a future date must be considered. In this review we outline the current evidence in the assessment and management of a transplant recipient with an AAVF. We will describe our recommended five-step approach to assessing an AAVF in transplant patients; 1.) Define AAVF 2.) Risk assess AAVF 3.) Assess transplant graft function and future graft failure risk 4.) Consider future renal replacement therapy options 5.) Vascular mapping to assess future vascular access options. Then we will describe the current therapeutic options and when they would most appropriately be employed.

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

Maximising organ utilisation from donation after circulatory death (DCD) donors could help meet some of the shortfall in organ supply, but it represents a major challenge, particularly as organ donors and transplant recipients become older and more medically complex over time. Success is dependent upon establishing common practices and accepted protocols that allow the safe sharing of DCD organs and maximise the use of the DCD donor pool. The British Transplantation Society 'Guideline on transplantation from deceased donors after circulatory death' has recently been updated. This manuscript summarises the relevant recommendations from chapters specifically related to transplantation of cardiothoracic organs.

The British transplantation society guidelines on organ donation from deceased donors after circulatory death.

Recipient outcomes after transplantation with organs from donation after circulatory death (DCD) donors can compare favourably and even match recipient outcomes after transplantation with organs from donation after brain death donors. Success is dependent upon establishing common practices and accepted protocols that allow the safe sharing of DCD organs and maximise the use of the DCD donor pool. The British Transplantation Society 'Guideline on transplantation from deceased donors after circulatory death' has recently been updated. This manuscript summarises the relevant recommendations from chapters specifically related to organ donation.

The Long-Term Impacts of an Integrated Care Programme on Hospital Utilisation among Older Adults in the South of England: A Synthetic Control Study.

Introduction: Reducing hospital use is often viewed as a possible positive consequence of introducing integrated care (IC). We investigated the impact of an IC programme in North East Hampshire and Farnham (NEHF), in southern England, on hospital utilisation among older adults over a 55 months period. Method: We used a Generalised Synthetic Control design to investigate the effect of implementing IC in NEHF between 2015 and 2020. For a range of hospital use outcomes, we estimated the trajectory that each would have followed in the absence of IC and compared it with the actual trajectory to estimate the potential impact of IC. Results: Three years into the programme, emergency admission rates started reducing in NEHF relative to its synthetic control, particularly those resulting in overnight hospital stays. By year 5 of the study overall emergency admission rates were 9.8% lower (95% confidence interval: -17.2% to -0.6%). We found no sustained difference in rates of emergency department (ED) visits, and average length of hospital stay was significantly higher from year 2. Conclusion: An IC programme in NEHF led to lower than estimated emergency admission rates; however, the interpretation of the impact of IC on admissions is complicated as lower rates did not appear until three years into the programme and the reliability of the synthetic control weakens over a long time horizon. There was no sustained change in ED visit rates.

Early evaluation of the Children and Young People's Mental Health Trailblazer programme: a rapid mixed-methods study.

Background: The Children and Young People's Mental Health Trailblazer programme is funding the creation of new mental health support teams to work in schools and further education colleges. Mental health support teams directly support children and young people with 'mild to moderate' mental health problems and work with school and college staff to promote well-being for all. A new workforce of education mental health practitioners is being trained for the teams. Objective(s): The National Institute for Health and Care Research Birmingham, RAND and Cambridge Evaluation Rapid Evaluation Centre and Policy Innovation and Evaluation Research Unit undertook an early evaluation of the Trailblazer programme to examine the development, implementation and early progress of mental health support teams in the programme's first 25 'Trailblazer' sites. Design: A mixed-methods evaluation, comprising three work packages: 1. Establishing the baseline and understanding the development and early impacts of the Trailblazer sites, including two rounds of surveys with key informants and participating education settings in all 25 sites. 2. More detailed research in five purposively selected Trailblazer sites, including interviews with a range of stakeholders and focus groups with children and young people. 3. Scoping and developing options for a longer-term assessment of the programme's outcomes and impacts. Fieldwork was undertaken between November 2020 and February 2022. The University of Birmingham Institute for Mental Health Youth Advisory Group was involved throughout the study, including co-producing the focus groups with children and young people. Results: Substantial progress had been made implementing the programme, in challenging circumstances, and there was optimism about what it had the potential to achieve. The education mental health practitioner role had proven popular, but sites reported challenges in retaining education mental health practitioners, and turnover left mental health support teams short-staffed and needing to re-recruit. Education settings welcomed additional mental health support and reported positive early outcomes, including staff feeling more confident and having faster access to advice about mental health issues. At the same time, there were concerns about children who had mental health problems that were more serious than 'mild to moderate' but not serious enough to be accepted for specialist help, and that the interventions offered were not working well for some young people. Mental health support teams were generally spending more time supporting children with mental health problems than working with education settings to develop 'whole school' approaches to mental health and well-being, and service models in some sites appeared to be more clinically oriented, with a strong focus on mental health support teams' therapeutic functions. Limitations: Despite efforts to maximise participation, survey response rates were relatively low and some groups were less well represented than others. We were not able to gather sufficiently detailed data to develop a typology of Trailblazer sites, as was planned. Conclusions: Key lessons for future programme implementation include: - Whether mental health support teams should expand support to children and young people with more complex and serious mental health problems. - How to keep the twin aims of prevention and early intervention in balance. - How to retain education mental health practitioners once trained. Future work: The findings have important implications for the design of a longer-term impact evaluation of the programme, which is due to commence in summer 2023. Study registration: Ethical approval from the University of Birmingham (ERN_19-1400 - RG_19-190) and London School of Hygiene and Tropical Medicine (Ref: 18040) and Health Research Authority approval (IRAS 270760). Funding: The Birmingham, RAND and Cambridge Evaluation Rapid Evaluation Centre is funded by the National Institute for Health and Care Research Health Services and Delivery Research programme (HSDR 16/138/31). The Policy Innovation and Evaluation Research Unit is funded by the NIHR Policy Research Programme (PR-PRU-1217-20602).

How does a local instrumental variable method perform across settings with instruments of differing strengths? A simulation study and an evaluation of emergency surgery.

Local instrumental variable (LIV) approaches use continuous/multi-valued instrumental variables (IV) to generate consistent estimates of average treatment effects (ATEs) and Conditional Average Treatment Effects (CATEs). There is little evidence on how LIV approaches perform according to the strength of the IV or with different sample sizes. Our simulation study examined the performance of an LIV method, and a two-stage least squares (2SLS) approach across different sample sizes and IV strengths. We considered four 'heterogeneity' scenarios: homogeneity, overt heterogeneity (over measured covariates), essential heterogeneity (unmeasured), and overt and essential heterogeneity combined. In all scenarios, LIV reported estimates with low bias even with the smallest sample size, provided that the instrument was strong. Compared to 2SLS, LIV provided estimates for ATE and CATE with lower levels of bias and Root Mean Squared Error. With smaller sample sizes, both approaches required stronger IVs to ensure low bias. We considered both methods in evaluating emergency surgery (ES) for three acute gastrointestinal conditions. Whereas 2SLS found no differences in the effectiveness of ES according to subgroup, LIV reported that frailer patients had worse outcomes following ES. In settings with continuous IVs of moderate strength, LIV approaches are better suited than 2SLS to estimate policy-relevant treatment effect parameters.