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University of Oxford
Protocol for a Group-Sequential Two-Stratum Multicenter Open-Label Randomized Clinical Trial of Respiratory Support in Infants with Acute Bronchiolitis: Breathing Assistance in Children with Bronchiolitis (BACHb)
Objectives: The Breathing Assistance in Children with bronchiolitis (BACHb) trial aims to evaluate the clinical and cost-effectiveness of high-flow nasal cannula (HFNC) therapy compared with humidified standard oxygen (HSO) in infants with moderate bronchiolitis, and HFNC with continuous positive airway pressure (CPAP) in severe bronchiolitis. Design: Pragmatic, group-sequential, two-stratum, multicenter, open-label randomized clinical trial. Setting: Fifty hospitals across England, Scotland, and Wales. Patients: Hospitalized infants younger than 12 months old with a clinical diagnosis of bronchiolitis, assessed at least twice 15 minutes apart to fulfill criteria for either severe bronchiolitis (one or more of: respiratory rate > 70 breaths/min, grunting, marked chest recession, recurrent short apneas) or moderate bronchiolitis (lack of response to low-flow oxygen, indicated by persistent hypoxemia and/or moderate respiratory distress). Interventions: "Moderate bronchiolitis stratum": HFNC at a flow rate of 2 L/kg/min vs. HSO through a facemask or headbox at a flow rate up to 15 L/min. "Severe bronchiolitis stratum": HFNC at a flow rate of 2 L/kg/min vs. CPAP pressure set at 6-8 cm H2O. Measurements and Main Results: In each stratum, eligible infants will be randomly allocated on a 1:1 basis to the trial treatments using a web-based system by permuted block randomization, stratified by site of recruitment and age (< 6 wk and ≥ 6 wk). Due to the emergency nature of the treatments, written informed consent will be deferred. The primary outcome is time from randomization to hospital discharge within 30 days. Baseline clinical characteristics and hospital course, including details of respiratory support, and discharge and cost-effectiveness outcomes will be collected. The trial received Health Research Authority and Research Ethics Committee approval from the Yorkshire and The Humber-South Yorkshire Research Ethics Committee on August 3, 2023 (reference: 23/YH/0166). The trial registration is ISRCTN52937119. Conclusions: Trial findings will be disseminated in national and international conferences, in peer-reviewed journals and through social media.
Health economic aspects of childhood excess weight
Background: Over the past four decades, the prevalence of childhood excess weight has risen significantly globally and remains high in many countries. In England, the prevalence of excess weight among Year 6 children (10–11-year-olds) increased from 31.6% in 2006/07 to 36.6% in 2022/23. Despite the increasing public health burden, substantial uncertainty persists regarding key economic parameters and outcomes necessary to guide research and inform policy for the efficient allocation of resources that target childhood excess weight. Methods: This thesis presents a structured review of economic aspects of childhood excess weight as a foundation for further analyses. A systematic review of economic evaluations of interventions targeting childhood excess weight was conducted, followed by an analysis of data from the UK Millennium Cohort Study to estimate transitions in childhood weight status. Additionally, electronic health records extracted from the Clinical Practice Research Datalink (CPRD), linked with Hospital Episode Statistics (HES), were analysed to estimate direct healthcare costs attributable to childhood excess weight. Results: The systematic review found that early prevention strategies for childhood excess weight are generally cost-effective. Analysis of data from the Millennium Cohort Study indicated that children aged 3 to 7 years had a significantly higher probability of transitioning from overweight or obesity to a healthy weight compared to older children, with more than twice the annual likelihood of such transitions. These movements between weight status categories were also influenced by child, maternal, and sociodemographic factors. My analyses of CPRD-HES data revealed that children living with overweight and obesity incurred significantly higher direct healthcare costs than their peers with a healthy weight. In comparison to children with healthy weight, those living with overweight generated additional costs of £133.93 and £66.32, on average, in the year preceding and following a BMI measurement, respectively, while children with obesity incurred additional costs of £115.47 and £154.51, on average, during the same periods. The total annual healthcare cost attributable to childhood excess weight in England was estimated at £0.3 billion. Conclusions: This thesis identifies critical areas for future economic research, offering insights for researchers and policymakers. It underscores the significance of investing early in cost-effective interventions to address childhood excess weight. The evidence presented in this thesis can serve as data inputs for future economic evaluations in this field.
Childhood Transitions Between Weight Status Categories: Evidence from the UK Millennium Cohort Study
Background: Assessing the cost-effectiveness of interventions targeting childhood excess weight requires estimates of the hazards of transitioning between weight status categories. Current estimates are based on studies characterized by insufficient sample sizes, a lack of national representativeness, and untested assumptions. Objectives: We sought to (1) estimate transition probabilities and hazard ratios for transitioning between childhood weight status categories, (2) test the validity of the underlying assumption in the literature that transitions between childhood bodyweight categories are time-homogeneous, (3) account for complex sampling procedures when deriving nationally representative transition estimates, and (4) explore the impact of child, maternal, and sociodemographic characteristics. Methods: We applied a multistate transition modeling approach accounting for complex survey design to UK Millennium Cohort Study (MCS) data to predict transition probabilities and hazard ratios for weight status movements for children aged 3–17. Surveys were conducted at ages 3 (wave 2 in 2004), 5 (wave 3 in 2006), 7 (wave 4 in 2008), 11 (wave 5 in 2012), 14 (wave 6 in 2015), and 17 (wave 7 in 2018) years. We derived datasets that included repeated body mass index measurements across waves after excluding multiple births and children with missing or implausible bodyweight records. To account for the stratified cluster sample design of the MCS, we incorporated survey weights and jackknife replicates of survey weights. Using a validation dataset from the MCS, we tested the validity of our models. Finally, we estimated the relationships between state transitions and child, maternal, and sociodemographic factors. Results: The datasets for our primary analysis consisted of 10,399 children for waves 2–3, 10,729 for waves 3–4, 9685 for waves 4–5, 8593 for waves 5–6, and 7085 for waves 6–7. All datasets consisted of roughly equal splits of boys and girls. Under the assumption of time-heterogeneous transition rates (our base-case model), younger children (ages 3–5 and 5–7 years) had significantly higher annual transition probabilities of moving from healthy weight to overweight (0.033, 95% confidence interval [CI] 0.026–0.041, and 0.027, 95% CI 0.021–0.033, respectively) compared to older children (0.015, 95% CI 0.012–0.018, at ages 7–11; 0.018, 95% CI 0.013–0.023, at ages 11–14; and 0.018, 95% CI 0.013–0.025 at ages 14–17 years). However, the resolution of unhealthy weight was more strongly age-dependent than transitions from healthy weight to non-healthy weight states. Transition hazards differed by child, maternal, and sociodemographic factors. Conclusions: Our models generated estimates of bodyweight status transitions in a representative UK childhood population. Compared to our scenario models (i.e., time-homogeneous transition rates), our base-case model fits the observed data best, indicating a non-time-homogeneous pattern in transitions between bodyweight categories during childhood. Transition hazards varied significantly by age and across subpopulations, suggesting that conducting subgroup-specific cost-effectiveness analyses of childhood weight management interventions will optimize decision-making.
Health Economic Aspects of Childhood Excess Weight: A Structured Review
An economic perspective is crucial to understand the broad consequences of childhood excess weight (CEW). These can manifest in the form of elevated health care and societal costs, impaired health status, or inefficiencies in the allocation of resources targeted at its prevention, management, or treatment. Although existing systematic reviews provide summaries of distinct economic research strands covering CEW, they have a restricted focus that overlooks relevant evidence. The overarching aim of this structured review was to update and enhance recent key reviews of four strands of economic evidence in this area, namely, (1) economic costs associated with CEW, (2) health utilities associated with CEW, (3) economic evaluations of interventions targeting CEW, and (4) economic determinants and broader consequences of CEW. Our de novo searches identified six additional studies for the first research strand, five studies for the second, thirty‐one for the third, and two for the fourth. Most studies were conducted in a small number of high‐income countries. Our review highlights knowledge gaps across all the research strands. Evidence from this structured review can act as data input into future economic evaluations in this area and highlights areas where future economic research should be targeted.
Thoracoscopic surgical ablation versus catheter ablation as first-line treatment for long-standing persistent atrial fibrillation: the CASA-AF RCT
BackgroundStandalone thoracoscopic surgical ablation may be more effective than catheter ablation in patients with long-standing persistent atrial fibrillation.ObjectivesTo determine whether or not surgical ablation is clinically superior to catheter ablation as the first-line treatment strategy in long-standing persistent atrial fibrillation.DesignThis was a prospective, multicentre, randomised control trial.SettingFour NHS tertiary centres in England.ParticipantsAdults with long-standing persistent atrial fibrillation, who had European Heart Rhythm Association symptom scores > 2 and who were naive to previous catheter ablation or thoracic/cardiac surgery.InterventionsMinimally invasive thoracoscopic surgical ablation and conventional catheter ablation (control intervention).Main outcome measuresThe primary outcome was freedom from atrial fibrillation/tachycardia ≥ 30 seconds after a single procedure without antiarrhythmic drugs (class 1C/3) at 1 year, excluding a 3-month blanking period. The secondary outcomes include the intervention-related major complication rate; clinical success (≥ 75% reduction in arrhythmia burden); and changes in symptoms, quality of life and cost-effectiveness.MethodsPatients (n = 120) were randomised to surgical ablation (n = 60) or catheter ablation (n = 60). An implanted loop recorder provided continuous cardiac monitoring following ablation. Follow-up visits were at 3, 6, 9 and 12 months. Loop recorder data were reviewed monthly by a physiologist who was blinded to the randomisation outcome.ResultsThe study treatment was received by 55 patients in the surgical ablation arm and 60 patients in the catheter ablation arm; five patients withdrew from surgical ablation before treatment. Data from randomised and treated patients were analysed as per intention to treat. Patients had a mean age of 62.3 (standard deviation 9.6) years, were predominantly male (74%), had a mean left atrial diameter of 44.6 mm (standard deviation 6 mm) and were in continuous atrial fibrillation for 22 months (range 16–31 months). At 12 months, 26% of patients in the surgical ablation arm (14/54) and 28% of patients in the catheter ablation arm (17/60) were free from atrial arrhythmias after a single procedure without antiarrhythmic drugs (odds ratio 1.13, 95% confidence interval 0.46 to 2.83; p = 0.84). An arrhythmia burden reduction of ≥ 75% was seen in 36 out of 54 (67%) patients in the surgical ablation arm, compared with 46 out of 60 (77%) patients in the catheter ablation arm (odds ratio 1.64, 95% confidence interval 0.67 to 4.08; p = 0.3). Procedure-related serious complications within 30 days of the intervention occurred in 15% (8/55) of patients in the surgical ablation arm (including one death) compared with 10% (6/60) of patients in the catheter ablation arm (p = 0.46). Surgical ablation was associated with significantly higher costs (£23,221 vs. £18,186; p = 0.02) and fewer quality-adjusted life-years than catheter ablation (0.76 vs. 0.83; p = 0.02).LimitationsThis study was conducted in four highly specialised cardiology centres that have substantial experience in both treatment modalities; therefore, the results may not be widely generalisable. The study was not powered to detect small differences in efficacy.ConclusionsWe found no evidence to suggest that standalone thoracoscopic surgical ablation outcomes were superior to catheter ablation outcomes in achieving freedom from atrial arrhythmia after a single procedure without antiarrhythmic drugs. Moreover, surgical ablation is associated with a longer hospital stay, smaller improvements in quality of life and higher health-care costs than catheter ablation (standard care therapy).Future workEvaluation of the impact of ablation treatments on sinus rhythm maintenance and quality of life with extended follow-up to 3 years. Model-based economic analysis to estimate long-term benefits, harms and costs of surgical and catheter ablation compared with antiarrhythmic drug therapy in long-standing persistent atrial fibrillation patients.Trial registrationCurrent Controlled Trials ISRCTN18250790 and ClinicalTrials.gov NCT02755688.FundingThis project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership. This study was supported by the UK Clinical Research Collaboration-registered King’s Clinical Trials Unit at King’s Health Partners, which is part funded by the NIHR Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and King’s College London and the NIHR Evaluation, Trials and Studies Coordinating Centre. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 8, No. 18. See the NIHR Journals Library website for further project information.
A duodenal sleeve bypass device added to intensive medical therapy for obesity with type 2 diabetes: a RCT
BackgroundThe EndoBarrier® (GI Dynamics Inc., Boston, MA, USA) is an endoluminal duodenal–jejunal bypass liner developed for the treatment of patients with obesity and type 2 diabetes mellitus. Meta-analyses of its effects on glycaemia and weight have called for larger randomised controlled trials with longer follow-up.ObjectivesThe primary objective was to compare intensive medical therapy with a duodenal–jejunal bypass liner with intensive medical therapy without a duodenal–jejunal bypass liner, comparing effectiveness on the metabolic state as defined by the International Diabetes Federation as a glycated haemoglobin level reduction of ≥ 20%. The secondary objectives were to compare intensive medical therapy with a duodenal–jejunal bypass liner with intensive medical therapy without a duodenal–jejunal bypass liner, comparing effectiveness on the metabolic state as defined by the International Diabetes Federation as a glycated haemoglobin level of DesignA multicentre, open-label, randomised controlled trial.SettingImperial College Healthcare NHS Trust and University Hospital Southampton NHS Foundation Trust.ParticipantsPatients aged 18–65 years with a body mass index of 30–50 kg/m2 and with inadequately controlled type 2 diabetes mellitus who were on oral glucose-lowering medications.InterventionsParticipants were randomised equally to receive intensive medical therapy alongside a duodenal–jejunal bypass liner device (n = 85) or intensive medical therapy alone for 12 months (n = 85), and were followed up for a further 12 months.ResultsThere was no significant difference between groups in the percentage of patients achieving the glycaemic primary or secondary outcomes [primary outcome at 12 months: duodenal–jejunal bypass liner group 54.5% vs. control group 55.2% (odds ratio 0.93, 95% confidence interval 0.44 to 1.98; p = 0.85); primary outcome at 24 months: duodenal–jejunal bypass liner group 39.7% vs. control group 36.5% (odds ratio 1.13, 95% confidence interval 0.52 to 2.47; p = 0.75)]. Significantly more patients in the duodenal–jejunal bypass liner group than in the control group lost > 15% of their total body weight (duodenal–jejunal bypass liner group 24.2% vs. control group 3.7%; odds ratio 8.33, 95% confidence interval 1.78 to 39.0; p = 0.007) and achieved blood pressure targets (duodenal–jejunal bypass liner group 68.2% vs. control group 44.4%; odds ratio 2.57, 95% confidence interval 1.21 to 5.48; p = 0.014). These differences were observed at 12 months but not at 24 months. There were more adverse events in the duodenal–jejunal bypass liner group, including one liver abscess. The increase in peripheral insulin sensitivity was superior in the duodenal–jejunal bypass liner group. Spectroscopic analyses of plasma, urine and faeces revealed several distinct metabolic perturbations in the duodenal–jejunal bypass liner group but not in the control group. Brain reward responses to food cues were not different between groups. The number of mean quality-adjusted life-years gained was similar in both groups and the additional costs of the duodenal–jejunal bypass liner may outweigh the value of the health benefits by £2560 per patient treated.ConclusionsThe results show that the endoluminal duodenal–jejunal bypass liner was not superior to intensive medical therapy for glycaemic control and was associated with more adverse events. The duodenal–jejunal bypass liner was associated with significant weight loss and improvement in cardiometabolic parameters at 12 months but not at 24 months. Economic evaluation showed that the bypass liner was not cost-effective for glycaemic control or for weight loss.Trial registrationCurrent Controlled Trials ISRCTN30845205.FundingThis project was funded by the Efficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 7, No. 6. See the NIHR Journals Library website for further project information. This study was executed with the support of GI Dynamics Inc. and with the kind support of Nutricia Advanced Medical Nutrition for providing oral nutritional supplements.
Catheter ablation vs. thoracoscopic surgical ablation in long-standing persistent atrial fibrillation: CASA-AF randomized controlled trial
Aims : Long-standing persistent atrial fibrillation (LSPAF) is challenging to treat with suboptimal catheter ablation (CA) outcomes. Thoracoscopic surgical ablation (SA) has shown promising efficacy in atrial fibrillation (AF). This multicentre randomized controlled trial tested whether SA was superior to CA as the first interventional strategy in de novo LSPAF. Methods and results : We randomized 120 LSPAF patients to SA or CA. All patients underwent predetermined lesion sets and implantable loop recorder insertion. Primary outcome was single procedure freedom from AF/atrial tachycardia (AT) ≥30 s without anti-arrhythmic drugs at 12 months. Secondary outcomes included clinical success (≥75% reduction in AF/AT burden); procedure-related serious adverse events; changes in patients' symptoms and quality-of-life scores; and cost-effectiveness. At 12 months, freedom from AF/AT was recorded in 26% (14/54) of patients in SA vs. 28% (17/60) in the CA group [OR 1.128, 95% CI (0.46-2.83), P = 0.83]. Reduction in AF/AT burden ≥75% was recorded in 67% (36/54) vs. 77% (46/60) [OR 1.13, 95% CI (0.67-4.08), P = 0.3] in SA and CA groups, respectively. Procedure-related serious adverse events within 30 days of intervention were reported in 15% (8/55) of patients in SA vs. 10% (6/60) in CA, P = 0.46. One death was reported after SA. Improvements in AF symptoms were greater following CA. Over 12 months, SA was more expensive and provided fewer quality-adjusted life-years (QALYs) compared with CA (0.78 vs. 0.85, P = 0.02). Conclusion : Single procedure thoracoscopic SA is not superior to CA in treating LSPAF. Catheter ablation provided greater improvements in symptoms and accrued significantly more QALYs during follow-up than SA. Clinical Trial Registration: ISRCTN18250790 and ClinicalTrials.gov: NCT02755688
Engaging adolescents in changing behaviour (EACH-B): a study protocol for a cluster randomised controlled trial to improve dietary quality and physical activity
Background: Poor diet and lack of physical activity are strongly linked to non-communicable disease risk, but modifying them is challenging. There is increasing recognition that adolescence is an important time to intervene; habits formed during this period tend to last, and physical and psychological changes during adolescence make it an important time to help individuals form healthier habits. Improving adolescents’ health behaviours is important not only for their own health now and in adulthood, but also for the health of any future children. Building on LifeLab—an existing, purpose-built educational facility at the University of Southampton—we have developed a multi-component intervention for secondary school students called Engaging Adolescents in Changing Behaviour (EACH-B) that aims to motivate and support adolescents to eat better and be more physically active. Methods: A cluster randomised controlled trial is being conducted to evaluate the effectiveness of the EACH-B intervention. The primary outcomes of the intervention are self-reported dietary quality and objectively measured physical activity (PA) levels, both assessed at baseline and at 12-month follow-up. The EACH-B intervention consists of three linked elements: professional development for teachers including training in communication skills to support health behaviour change; the LifeLab educational module comprising in-school teaching of nine science lessons linked to the English National Curriculum and a practical day visit to the LifeLab facility; and a personalised digital intervention that involves social support and game features that promote eating better and being more active. Both the taught module and the LifeLab day are designed with a focus on the science behind the messages about positive health behaviours, such as diet and PA, for the adolescents now, in adulthood and their future offspring, with the aim of promoting personal plans for change. The EACH-B research trial aims to recruit approximately 2300 secondary school students aged 12–13 years from 50 schools (the clusters) from Hampshire and neighbouring counties. Participating schools will be randomised to either the control or intervention arm. The intervention will be run during two academic years, with continual recruitment of schools throughout the school year until the sample size is reached. The schools allocated to the control arm will receive normal schooling but will be offered the intervention after data collection for the trial is complete. An economic model will be developed to assess the cost-effectiveness of the EACH-B intervention compared with usual schooling. Discussion: Adolescents’ health needs are often ignored and they can be difficult to engage in behaviour change. Building a cheap, sustainable way of engaging them in making healthier choices will benefit their long-term health and that of their future children. Trial registration: ISRCTN 74109264. Registered on 30 August 2019. EACH-B is a cluster randomised controlled trial, funded by the National Institute for Health Research (RP-PG-0216-20004).
Fulvestrant for Untreated Hormone-Receptor Positive Locally Advanced or Metastatic Breast Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal
Clinical and cost-effectiveness evidence on fulvestrant for untreated hormone-receptor positive locally advanced or metastatic breast cancer was submitted to the single technology appraisal process of the National Institute for Health and Care Excellence by the manufacturer of fulvestrant. The Southampton Health Technology Assessments Centre was commissioned by the National Institute for Health and Care Excellence as an independent Evidence Review Group to critique the company’s submitted evidence. Fulvestrant was compared directly with anastrozole in two randomised controlled trials and was compared indirectly by means of a network meta-analysis with anastrozole, letrozole and tamoxifen. This article summarises the Evidence Review Group’s review of the company’s submission and summarises the guidance the National Institute for Health and Care Excellence Appraisal Committee issued in January 2018. The Evidence Review Group had several concerns, the most important of which related to the degree to which fulvestrant might confer a benefit in overall survival. This was because mature data were not available from the key phase III trial FALCON. The economic model was sensitive to changes in overall survival and the Evidence Review Group considered the incremental cost-effectiveness ratio was uncertain and likely to increase once mature results from FALCON become available. The National Institute for Health and Care Excellence Appraisal Committee concluded that fulvestrant could not be recommended for treating locally advanced or metastatic estrogen-receptor-positive breast cancer in postmenopausal women who have not received previous endocrine therapy.
Two interferon gamma release assays for predicting active tuberculosis: The UK PREDICT TB prognostic test study
Background: Despite a recent decline in the annual incidence of tuberculosis (TB) in the UK, rates remain higher than in most Western European countries. The detection and treatment of latent TB infection (LTBI) is an essential component of the UK TB control programme. Objectives: To assess the prognostic value and cost-effectiveness of the current two interferon gamma release assays (IGRAs) compared with the standard tuberculin skin test (TST) for predicting active TB among untreated individuals at increased risk of TB: (1) contacts of active TB cases and (2) new entrants to the UK from high-TB-burden countries. Design: A prospective cohort study and economic analysis. Participants and setting: Participants were recruited in TB clinics, general practices and community settings. Contacts of active TB cases and migrants who were born in high-TB-burden countries arriving in the UK were eligible to take part if they were aged ≥ 16 years. Main outcome measures: Outcomes include incidence rate ratios comparing the incidence of active TB in those participants with a positive test result and those with a negative test result for each assay, and combination of tests and the cost per quality-adjusted life-year (QALY) for each screening strategy. Results: A total of 10,045 participants were recruited between May 2010 and July 2015. Among 9610 evaluable participants, 97 (1.0%) developed active TB. For the primary analysis, all test data were available for 6380 participants, with 77 participants developing active TB. A positive result for TSTa (positive if induration is ≥ 5 mm) was a significantly poorer predictor of progression to active TB than a positive result for any of the other tests. Compared with TSTb [positive if induration is ≥ 6 mm without prior bacillus Calmette–Guérin (BCG) alone, T-SPOT®.TB (Oxford Immunotec Ltd, Oxford, UK), TSTa + T-SPOT.TB, TSTa + IGRA and the three combination strategies including TSTb were significantly superior predictors of progression. Compared with the T-SPOT.TB test alone, TSTa + T-SPOT.TB, TSTb + QuantiFERON® TB Gold In-Tube (QFT-GIT; QIAGEN GmbH, Hilden, Germany) and TSTb + IGRA were significantly superior predictors of progression and, compared with QFT-GIT alone, T-SPOT.TB, TSTa + T-SPOT.TB, TSTa + QFT-GIT, TSTa + IGRA, TSTb + T-SPOT.TB, TSTb + QFT-GIT and TSTb + IGRA were significantly superior predictors of progression. When evaluating the negative predictive performance of tests and strategies, negative results for TSTa + QFT-GIT were significantly poorer predictors of non-progression than negative results for TSTa, T-SPOT.TB and TSTa + IGRA. The most cost-effective LTBI testing strategies are the dual-testing strategies. The cost and QALY differences between the LTBI testing strategies were small; in particular, QFT-GIT, TSTb + T-SPOT.TB and TSTb + QFT-GIT had very similar incremental net benefit estimates. Conclusion: This study found modest differences between tests, or combinations of tests, in identifying individuals who would go on to develop active TB. However, a two-step approach that combined TSTb with an IGRA was the most cost-effective testing option. Implications for practice and future research: The two-step TSTb strategy, which stratified the TST by prior BCG vaccination followed by an IGRA, was the most cost-effective approach. The limited ability of current tests to predict who will progress limits the clinical utility of tests. The implications of these results for the NHS England/Public Health England national TB screening programme for migrants should be investigated.
Psychometric Performance of Generic Childhood Multi-Attribute Utility Instruments in Preterm and Low Birthweight Populations: A Systematic Review
Background: Individuals born preterm (gestational age < 37 weeks) and/or at low birthweight (<2500 g) are at increased risk of health impairments from birth to adulthood. This review aimed to evaluate the psychometric performance of generic childhood-specific or childhood-compatible multi-attribute utility instruments (MAUIs) in preterm and/or low birthweight (PLB) populations. Methods: Searches covered seven databases, including studies that targeted childhood (aged < 18 years) and/or adult (≥18 years) PLB populations; provided psychometric evidence for generic childhood-specific or compatible MAUI(s) (any language version); and published in English. Eighteen psychometric properties were evaluated using a four-part criteria rating system. Data syntheses identified psychometric evidence gaps and summarised the psychometric assessment methods/results. Results: A total of 42 studies were included, generating 178 criteria rating outputs across four MAUIs: 17D, CHSCS-PS, HUI2, and HUI3. Moreover, 64.0% of outputs concerned the HUI3 MAUI, and 38.2% related to known-group validity. There was no evidence for five psychometric properties. Only 6.7% of outputs concerned reliability and proxy–child agreement. No MAUI outperformed others across all properties. The frequently applied HUI2 and HUI3 lacked content validity evidence. Conclusions: This psychometric evidence catalogue should inform the selection of MAUI(s) suited to the specific aims of applications targeting PLB populations. Further psychometric research is warranted to address the gaps in psychometric evidence.
A systematic review of economic evaluations of interventions targeting childhood overweight and obesity
This systematic review critically appraised and synthesized evidence from economic evaluations of interventions targeting childhood excess weight. We conducted systematic searches in 11 databases from inception to April 19, 2023. Studies were eligible if they evaluated interventions targeting children up to 18 years and the study intervention(s) targeted childhood excess weight or sought to improve diet or physical activity, regardless of the type of economic evaluation or the underpinning study design. We synthesized evidence using narrative synthesis methods. One-hundred fifty-one studies met the eligibility criteria and were classified into three groups based on the intervention approach: prevention-only (13 studies), prevention and treatment (100 studies), and treatment-only (38 studies). The predominant setting and study design differed considerably between the three groups of studies. However, compared with usual care, most interventions were deemed cost-effective. The study participants' ages, sex, and socioeconomic status were crucial to intervention cost-effectiveness. Interventions whose effects were projected beyond childhood, such as bariatric surgery, lower protein infant formula, and home-based general practitioner consultations, tended to be cost-effective. However, cost-effectiveness was sensitive to the assumptions underlying the persistence and intensity of such effects. Our findings can inform future recommendations on the conduct of economic evaluations of interventions targeting childhood overweight and obesity, as well as practice and policy recommendations.
Child Body Mass Index and Health Care Costs in England
Importance: In England, 27% of children aged 2 to 15 years live with overweight or obesity. However, national estimates of excess health care costs attributable to unhealthy weight status are lacking. Objective: To estimate health care costs associated with childhood weight status, stratified by sex, age, and ethnicity, in England. Design, Setting, and Participants: This retrospective cross-sectional study used 2014 to 2020 Clinical Practice Research Datalink Aurum data linked with Hospital Episode Statistics at general practices in England. Children aged 2 to 15 years with at least 1 body mass index (BMI) measurement recorded during a general practice visit between January 1, 2015, and March 30, 2019, for whom primary care and linked Hospital Episode Statistics data were available were studied. The analysis was conducted from December 11, 2023, to March 17, 2025. Exposure: BMI-derived weight status categories. Main Outcomes and Measures: Total health care costs were analyzed for the 1-year period before and after BMI measurement. Attributable health care costs were estimated using 2-part generalized linear models, adjusted for sex, age, ethnicity, socioeconomic status, and geographic region. Results: The study included the health care records of 268 231 unique children (mean [SD] age, 6.82 [2.66] years; 148 230 [55%] male; 4554 [2%] Bangladeshi, 16 708 [6%] Black, 7778 [3%] Chinese or other Asian, 7665 [3%] Indian, 10 875 [4%] Pakistani, 169 299 [63%] White, 10 886 [4%] multiracial, and 40 466 [15%] other or unknown). Before BMI measurement, health care costs were higher for children with overweight, obesity, and severe obesity but lower for children with underweight compared with children with healthy weight. After BMI measurement, costs were higher in children with underweight, overweight, obesity, and severe obesity compared with children with healthy weight. Severe obesity had the highest mean annual excess costs at £190 (95% CI, £77-£302) (US $274 [95% CI, US $111-US $435]) followed by underweight at £164 (95% CI, £69-£260) (US $236 [95% CI, US $99-US $374]). Health care costs varied by sex, age group, and ethnicity, although interactions were limited to specific BMI categories and covariate levels. The excess annual national health care cost attributable to overweight and obesity was £0.27 billion (95% CI, £0.12 billion to £0.43 billion) (US $0.39 billion [95% CI, US $0.17 billion to US $0.62 billion]). Conclusions and Relevance: In this cross-sectional study of children, health care costs were higher for nearly all unhealthy weight categories compared with healthy weight BMI measurement. These findings support the economic case for preventive and therapeutic interventions targeting unhealthy childhood weight and offer cost estimates for use in cost-effectiveness analyses.
Optimising strategies to address mental ill-health in doctors and medical students: 'Care under Pressure' realist review and implementation guidance
Background: Mental ill-health in health professionals, including doctors, is a global and growing concern. The existing literature on interventions that offer support, advice and/or treatment to sick doctors has not yet been synthesised in a way that considers the complexity and heterogeneity of the interventions, and the many dimensions of the problem. We (1) reviewed interventions to tackle doctors' and medical students' mental ill-health and its impacts on the clinical workforce and patient care - drawing on diverse literature sources and engaging iteratively with diverse stakeholder perspectives - and (2) produced recommendations that support the tailoring, implementation, monitoring and evaluation of contextually sensitive strategies to tackle mental ill-health and its impacts. Methods: Realist literature review consistent with the RAMESES quality and reporting standards. Sources for inclusion were identified through bibliographic database searches supplemented by purposive searches - resulting also from engagement with stakeholders. Data were extracted from included articles and subjected to realist analysis to identify (i) mechanisms causing mental ill-health in doctors and medical students and relevant contexts or circumstances when these mechanisms were likely to be 'triggered' and (ii) 'guiding principles' and features underpinning the interventions and recommendations discussed mostly in policy document, reviews and commentaries. Results: One hundred seventy-nine records were included. Most were from the USA (45%) and were published since 2009 (74%). The analysis showed that doctors were more likely to experience mental ill-health when they felt isolated or unable to do their job and when they feared repercussions of help-seeking. Healthy staff were necessary for excellent patient care. Interventions emphasising relationships and belonging were more likely to promote wellbeing. Interventions creating a people-focussed working culture, balancing positive/negative performance and acknowledging positive/negative aspects of a medical career helped doctors to thrive. The way that interventions were implemented seemed critically important. Doctors and medical students needed to have confidence in an intervention for the intervention to be effective. Conclusions: Successful interventions to tackle doctors' and students' mental ill-health are likely to be multidimensional and multilevel and involve multiple stakeholders. Evaluating and improving existing interventions is likely to be more effective than developing new ones. Our evidence synthesis provides a basis on which to do this. Study registration: PROSPERO CRD42017069870. Research project webpage http://sites.exeter.ac.uk/cup/
Interventions to improve antimicrobial prescribing of doctors in training (IMPACT): a realist review
BackgroundInterventions to improve the antimicrobial prescribing practices of doctors have been implemented widely to curtail the emergence and spread of antimicrobial resistance, but have been met with varying levels of success.ObjectivesThis study aimed to generate an in-depth understanding of how antimicrobial prescribing interventions ‘work’ (or do not work) for doctors in training by taking into account the wider context in which prescribing decisions are enacted.DesignThe review followed a realist approach to evidence synthesis, which uses an interpretive, theory-driven analysis of qualitative, quantitative and mixed-methods data from relevant studies.SettingPrimary and secondary care.ParticipantsNot applicable.InterventionsStudies related to antimicrobial prescribing for doctors in training.Main outcome measuresNot applicable.Data sourcesEMBASE (via Ovid), MEDLINE (via Ovid), MEDLINE In-Process & Other Non-Indexed Citations (via Ovid), PsycINFO (via Ovid), Web of Science core collection limited to Science Citation Index Expanded (SCIE) and Conference Proceedings Citation Index – Science (CPCI-S) (via Thomson Reuters), Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews, the Health Technology Assessment (HTA) database (all via The Cochrane Library), Applied Social Sciences Index and Abstracts (ASSIA) (via ProQuest), Google Scholar (Google Inc., Mountain View, CA, USA) and expert recommendations.Review methodsClearly bounded searches of electronic databases were supplemented by citation tracking and grey literature. Following quality standards for realist reviews, the retrieved articles were systematically screened and iteratively analysed to develop theoretically driven explanations. A programme theory was produced with input from a stakeholder group consisting of practitioners and patient representatives.ResultsA total of 131 articles were included. The overarching programme theory developed from the analysis of these articles explains how and why doctors in training decide to passively comply with or actively follow (1) seniors’ prescribing habits, (2) the way seniors take into account prescribing aids and seek the views of other health professionals and (3) the way seniors negotiate patient expectations. The programme theory also explains what drives willingness or reluctance to ask questions about antimicrobial prescribing or to challenge the decisions made by seniors. The review outlines how these outcomes result from complex inter-relationships between the contexts of practice doctors in training are embedded in (hierarchical relationships, powerful prescribing norms, unclear roles and responsibilities, implicit expectations about knowledge levels and application in practice) and the mechanisms triggered in these contexts (fear of criticism and individual responsibility, reputation management, position in the clinical team and appearing competent). Drawing on these findings, we set out explicit recommendations for optimal tailoring, design and implementation of antimicrobial prescribing interventions targeted at doctors in training.LimitationsMost articles included in the review discussed hospital-based, rather than primary, care. In cases when few data were available to fully capture all the nuances between context, mechanisms and outcomes, we have been explicit about the strength of our arguments.ConclusionsThis review contributes to our understanding of how antimicrobial prescribing interventions for doctors in training can be better embedded in the hierarchical and interprofessional dynamics of different health-care settings.Future workMore work is required to understand how interprofessional support for doctors in training can contribute to appropriate prescribing in the context of hierarchical dynamics.Study registrationThis study is registered as PROSPERO CRD42015017802.FundingThe National Institute for Health Research Health Services and Delivery Research programme.
BMJ open'care under pressure': A realist review of interventions to tackle doctors' mental ill-health and its impacts on the clinical workforce and patient care
Introduction Mental ill-health is prevalent across all groups of health professionals and this is of great concern in many countries. In the UK, the mental health of the National Health Service (NHS) workforce is a major healthcare issue, leading to presenteeism, absenteeism and loss of staff from the workforce. Most interventions targeting doctors aim to increase their 'productivity' and 'resilience', placing responsibility for good mental health with doctors themselves and neglecting the organisational and structural contexts that may have a detrimental effect on doctors' well-being. There is a need for approaches that are sensitive to the contextual complexities of mental ill-health in doctors, and that do not treat doctors as a uniform body, but allow distinctions to account for particular characteristics, such as specialty, career stage and different working environments. Methods and analysis Our project aims to understand how, why and in what contexts support interventions can be designed to minimise the incidence of doctors' mental ill-health. We will conduct a realist review-A form of theory-driven interpretative systematic review-of interventions, drawing on diverse literature sources. The review will iteratively progress through five steps: (1) locate existing theories; (2) search for evidence; (3) select articles; (4) extract and organise data and (5) synthesise evidence and draw conclusions. The analysis will summarise how, why and in what circumstances doctors' mental ill-health is likely to develop and what can remediate the situation. Throughout the project, we will also engage iteratively with diverse stakeholders in order to produce actionable theory. Ethics and dissemination Ethical approval is not required for our review. Our dissemination strategy will be participatory. Tailored outputs will be targeted to: policy makers; NHS employers and healthcare leaders; team leaders; support organisations; doctors experiencing mental ill-health, their families and colleagues.