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Objective: To estimate resource use and costs associated with peripartum hysterectomy for the English National Health Service.Design/setting: Analysis of linked Clinical Practice Research Datalink and Hospital Episodes Statistics (CPRD-HES) data.Population: Women undergoing peripartum hysterectomy between 1997 and 2013 and matched controls.Methods: Inverse probability weighted generalised estimating equations were used to model the non-linear trend in healthcare service use and costs over time, accounting for missing data, adjusting for maternal age, body mass index, delivery year, smoking and socio-economic indicators.Main Outcome Measures: Primary care, hospital outpatient and inpatient attendances and costs (UK 2015 prices).Results: The study sample included 1362 women (192 cases and 1170 controls) who gave birth between 1997 and 2013; 1088 (153 cases and 935 controls) of these were deliveries between 2003 and 2013 when all categories of hospital resource use were available. Based on the 2003-2013 delivery cohort, peripartum hysterectomy was associated with a mean adjusted additional total cost of £5380 (95% CI £4436-6687) and a cost ratio of 1.76 (95% CI 1.61-1.98) over 5 years of follow up compared with controls. Inpatient costs, mostly incurred during the first year following surgery, accounted for 78% excluding or 92% including delivery-related costs.Conclusion: Peripartum hysterectomy is associated with increased healthcare costs driven largely by increased post-surgery hospitalisation rates. To reduce healthcare costs and improve outcomes for women who undergo hysterectomy, interventions that reduce avoidable repeat hospitalisations following surgery such as providing active follow up, treatment and support in the community should be considered.Tweetable Abstract: A large amount of NHS data on peripartum hysterectomy suggests active community follow up could reduce costs, #HealthEconomics. [ABSTRACT FROM AUTHOR]

Background Overweight or obese individuals with type 2 diabetes are encouraged to lose weight for optimal glucose management, yet many find this difficult. Determining whether alterations in dietary patterns irrespective of weight loss can aid glucose control has not been fully investigated. Methods We conducted a systematic review and meta-analysis aiming to determine the effects of a Mediterranean diet compared to other dietary interventions on glycaemic control irrespective of weight loss. Electronic databases were searched for controlled trials that included a Mediterranean diet intervention. The interventions included all major components of the Mediterranean diet and were carried out in free-living individuals at high risk or diagnosed with type 2 diabetes. Network meta-analysis compared all interventions with one another at the same time as maintaining randomisation. Analyses were conducted within a Bayesian framework. Results Eight studies met the inclusion criteria, seven examined fasting blood glucose ( n = 972), six examined fasting insulin ( n = 1330) and three examined Hb A1c ( n = 487). None of the interventions were significantly better than the others in lowering glucose parameters. The Mediterranean diet reduced Hb A1c significantly compared to usual care but not compared to the Palaeolithic diet. Conclusions The effect of alterations in dietary practice irrespective of weight loss on glycaemic control cannot be concluded from the present review. The need for further research in this area is apparent because no firm conclusions about relative effectiveness of interventions could be drawn as a result of the paucity of the evidence. [ABSTRACT FROM AUTHOR]

Pesticides are chemicals used to enhance crop production. However, their residues can persist and accumulate in various environmental settings. This study assessed the occurrence of pesticide residues and ecological risks in surface water and sediment from the Libga and Builpela dams in northern Ghana. A total of 42 pesticides were analysed. Toxic units were used to assess the acute risk to sediment-dwelling organisms and aquatic biota. Risk quotients were employed to assess the chronic risk to aquatic organisms. Chlorpyrifos, atrazine, profenofos, and chlorfenvinphos were the main chemicals found in surface water. The concentrations were highest near the Builpela dam (0.413μg/L, 2.927μg/L, 0.304μg/L, 0.692μg/L, 0.073μg/L, 0.290μg/L, 0.06μg/L, and absent in the Libga dam). In the sediment, the organophosphates pyrimiphos-methyl and chlorpyrifos were found at high concentrations. They were found in higher quantities in the Libga dam (0.554mg/kg and 0.052mg/kg, respectively) and Builpela dam (0.051mg/kg and 0.043mg/kg, respectively). For organochlorines, p,p'-DDE and p,p'-DDD were the main residues detected at high concentrations. However, concentrations were higher for p,p'-DDD at Builpela than for p,p'-DDE. Additionally, high concentrations of atrazine were detected in this study. The toxic units showed a high acute risk for organisms that live in sediment as a result of chlorpyrifosfos and chlorfenvinphos residues. Similarly, pirimiphos-methyl and chlorfenvinphos, followed by chlorpyrifos, contributed to high acute risk in aquatic invertebrates. Risk quotients showed that both dams had a high long-term risk for aquatic life; however, the risk was higher at the Builpela dam due to Pirimiphos-methyl and Chlorfenvinphos. Ghana's pesticide regulations are less comprehensive and enforcement is often weaker in protecting aquatic organisms. It is recommended to enforce strict limits on pesticide residues. Additionally, there is a need to regularly review and update these regulations based on new scientific data to protect aquatic ecosystems., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Orou-Seko et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Adequate preparedness of health systems, particularly healthcare workers (HCWs), to respond to COVID-19 is critical for the effective control of the virus, especially in low- and middle-income countries where health systems are overburdened. We examined Ghanaian HCWs' perceived preparedness to respond to the pandemic and the factors that shaped their preparedness and that of the health system. Semi-structured in-depth interviews were conducted with n = 26 HCWs responsible for the clinical management of COVID-19 patients and three administrators responsible for developing and implementing COVID-19 policies at the facility level. Interviews were conducted over the phone in English, transcribed, and analyzed using a thematic analysis approach. Generally, HCWs felt inadequately prepared to contain the spread of COVID-19 due to resource shortages and inadequate training. HCWs, similarly, perceived the health system to be unprepared due to insufficient clinical infrastructure and logistical challenges. The few who felt prepared identified readiness in managing high consequence infectious disease cases and pre-existing protocols as enablers of HCW preparedness. The health system and HCWs were unprepared to manage the COVID-19 pandemic due to inadequate training, logistical challenges, and weak clinical infrastructure. Interventions are urgently needed to improve the health system's preparedness for future pandemics., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Odiase et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: After surgery for a broken ankle, patients are usually instructed to avoid walking for 6 weeks (delayed weight-bearing). Walking 2 weeks after surgery (early weight-bearing) might be a safe and preferable rehabilitation strategy. This study aimed to determine the clinical and cost effectiveness of an early weight-bearing strategy compared with a delayed weight-bearing strategy., Methods: This was a pragmatic, multicentre, randomised, non-inferiority trial including 561 participants (aged ≥18 years) who received acute surgery for an unstable ankle fracture in 23 UK National Health Service (NHS) hospitals who were assigned to either a delayed weight-bearing (n=280) or an early weight-bearing rehabilitation strategy (n=281). Patients treated with a hindfoot nail, those who did not have protective ankle sensation (eg, peripheral neuropathy), did not have the capacity to consent, or did not have the ability to adhere to trial procedures were excluded. Neither participants nor clinicians were masked to the treatment. The primary outcome was ankle function measured using the Olerud and Molander Ankle Score (OMAS) at 4 months after randomisation, in the per-protocol population. The pre-specified non-inferiority OMAS margin was -6 points and superiority testing was included in the intention-to-treat population in the event of non-inferiority. The trial was prospectively registered with ISRCTN Registry, ISRCTN12883981, and the trial is closed to new participants., Findings: Primary outcome data were collected from 480 (86%) of 561 participants. Recruitment was conducted between Jan 13, 2020, and Oct 29, 2021. At 4 months after randomisation, the mean OMAS score was 65·9 in the early weight-bearing and 61·2 in the delayed weight-bearing group and adjusted mean difference was 4·47 (95% CI 0·58 to 8·37, p=0·024; superiority testing adjusted difference 4·42, 95% CI 0·53 to 8·32, p=0·026) in favour of early weight-bearing. 46 (16%) participants in the early weight-bearing group and 39 (14%) in the delayed weight-bearing group had one or more complications (adjusted odds ratio 1·18, 95% CI 0·80 to 1·75, p=0·40). The mean costs from the perspective of the NHS and personal social services in the early and delayed weight-bearing groups were £725 and £785, respectively (mean difference -£60 [95% CI -342 to 232]). The probability that early weight-bearing is cost-effective exceeded 80%., Interpretation: An early weight-bearing strategy was found to be clinically non-inferior and highly likely to be cost-effective compared with the current standard of care (delayed weight-bearing)., Funding: National Institute for Health and Care Research (NIHR), NIHR Barts Biomedical Research Centre, and NIHR Applied Research Collaboration Oxford and Thames Valley., Competing Interests: Declaration of interests CPB, JA, SP, DA, RK, HC, and XLG report receiving grants from the National Institute for Health and Care Research, paid to their host institution. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

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., (© 2024. Crown.)

Objective: To investigate the impact of pre-existing painful musculoskeletal conditions on healthcare utilization and costs among patients with five common conditions: acute coronary syndrome (ACS), stroke, cancer, dementia and pneumonia., Methods: Using primary and secondary care services data from electronic health records, a negative binomial regression model was used to compare resource use while a two-part model was used to compare costs across the five conditions, between those with and without a pre-existing musculoskeletal pain., Results: The study included 760,792 patients (144,870 with ACS, 121,208 with stroke, 231,702 with cancer, 134,638 with dementia, and 128,374 with pneumonia) in the complete case analysis. Pre-existing musculoskeletal pain had an incident rate ratio of above one for most healthcare resources over the follow-up period and an adjusted additional mean cumulative total healthcare costs per patient of £674.59 (95%CI 570.30 to 778.87) for ACS; £613.34 (95%CI 496.87 to 729.82) for stroke; £459.26 (95%CI 376.60 to 541.91) for cancer; and £766.23 (95%CI 655.06 to 877.39) for dementia over five years after diagnosis; and £200.85 (95%CI 104.16 to 297.55) for pneumonia over one year after diagnosis compared to those without musculoskeletal pain., Conclusion: This study highlights that individuals with painful musculoskeletal conditions have higher healthcare utiliszation and costs than those without painful musculoskeletal conditions. Given the high occurrence of musculoskeletal pain in patients with other conditions, effective management strategies are needed to reduce the burden on healthcare resources.

Aim: Excess weight increases the risk of morbidity following colorectal cancer surgery. Weight loss may improve morbidity, but it is uncertain whether patients can follow an intensive weight loss intervention while waiting for surgery and there are concerns about muscle mass loss. The aim of this trial is to assess the feasibility of intentional weight loss in this setting and determine progression to a definitive trial., Methods: CARE is a prospectively registered, multicentre, feasibility, parallel, randomised controlled trial with embedded evaluation and optimisation of the recruitment process. Participants with excess weight awaiting curative colorectal resection for cancer are randomised 1:1 to care as usual or a low-energy nutritionally-replete total diet replacement programme with weekly remote behavioural support by a dietitian. Progression criteria will be based on the recruitment, engagement, adherence, and retention rates. Data will be collected on the 30-day postoperative morbidity, the typical primary outcome of prehabilitation trials. Secondary outcomes will include, among others, length of hospital stay, health-related quality of life, and body composition. Qualitative interviews will be used to understand patients' experiences of and attitudes towards trial participation and intervention engagement and adherence., Conclusion: CARE will evaluate the feasibility of intensive intentional weight loss as prehabilitation before colorectal cancer surgery. The results will determine the planning of a definitive trial., (© 2023 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

Despite successes in malaria control interventions over the past two decades, malaria remains a major public health concern. Over 125 million women live in endemic areas and experience adverse pregnancy outcomes due to malaria. Understanding health workers' perspectives on malaria identification and management is important to informing policy changes on the control and eradication of the disease. This study explored the perspectives of health workers on malaria case identification and management among pregnant women in Savelugu Municipality, Ghana. A qualitative study with a phenomenology design was conducted among participants. Participants were purposively selected and interviewed using a semi-structured interview guide. Thematic analysis was performed and the results were presented as themes and sub-themes. Four themes and eight sub-themes regarding case identification and management of malaria in pregnancy were identified including malaria case identification training (trained and untrained), identification approach (signs/symptoms and routine laboratory test), diagnostic tools (rapid diagnostic test and microscopy) and management options. It revealed that attending malaria training programs was generally optional. Some of the participants had not undergone any refresher training for malaria identification after their formal training at health institutions. Participants identified malaria by its signs and symptoms. However, they often referred clients for routine laboratory tests for confirmation. When malaria is confirmed in pregnancy, quinine is used for first trimester treatment, while Artemisinin-based Combination Therapies are prescribed after the first trimester. Clindamycin was not used in the first trimester treatment. This study found that training programs were optional for health workers. Some participants have not received refresher training after graduating from health institutions. Treatment of confirmed cases did not include clindamycin for first trimester malaria infections. Malaria refresher training programs should be made mandatory for health workers. Every suspected case should be confirmed using Rapid Diagnostic Test or microscopy before treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background and Objectives: Chronic headache disorders are a major cause of pain and disability. Education and supportive self-management approaches could reduce the burden of headache disability. We tested the effectiveness of a group educational and supportive self-management program for people living with chronic headaches., Methods: This was a pragmatic randomized controlled trial. Participants were aged 18 years or older with chronic migraine or chronic tension-type headache, with or without medication overuse headache. We primarily recruited from general practices. Participants were assigned to either a 2-day group education and self-management program, a one-to-one nurse interview, and telephone support or to usual care plus relaxation material. The primary outcome was headache related-quality of life using the Headache Impact Test (HIT)-6 at 12 months. The primary analysis used intention-to-treat principles for participants with migraine and both baseline and 12-month HIT-6 data., Results: Between April 2017 and March 2019, we randomized 736 participants. Because only 9 participants just had tension-type headache, our main analyses were on the 727 participants with migraine. Of them, 376 were allocated to the self-management intervention and 351 to usual care. Data from 586 (81%) participants were analyzed for primary outcome. There was no between-group difference in HIT-6 (adjusted mean difference = -0.3, 95% CI -1.23 to 0.67) or headache days (0.9, 95% CI -0.29 to 2.05) at 12 months. The Chronic Headache Education and Self-management Study intervention generated incremental adjusted costs of £268 (95% CI, £176-£377) (USD383 [95% CI USD252-USD539]) and incremental adjusted quality-adjusted life years (QALYs) of 0.031 (95% CI -0.005 to 0.063). The incremental cost-effectiveness ratio was £8,617 (USD12,322) per QALY gained., Discussion: These findings conclusively show a lack of benefit for quality of life or monthly headache days from a brief group education and supportive self-management program for people living with chronic migraine or chronic tension-type headache with episodic migraine., Trial Registration Information: Registered on the International Standard Randomized Controlled Trial Number registry, ISRCTN79708100 16th December 2015 doi.org/10.1186/ISRCTN79708100. The first enrollment was April 24, 2017., Classification of Evidence: This study provides Class III evidence that a brief group education and self-management program does not increase the probability of improvement in headache-related quality of life in people with chronic migraine., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: The Headache Impact Test (HIT-6) and the Chronic Headache Questionnaire (CH-QLQ) measure headache-related quality of life but are not preference-based and therefore cannot be used to generate health utilities for cost-effectiveness analyses. There are currently no established algorithms for mapping between the HIT-6 or CH-QLQ and preference-based health-related quality-of-life measures for chronic headache population., Methods: We developed algorithms for generating EQ-5D-5L and SF-6D utilities from the HIT-6 and the CHQLQ using both direct and response mapping approaches. A multi-stage model selection process was used to assess the predictive accuracy of the models. The estimated mapping algorithms were derived to generate UK tariffs and was validated using the Chronic Headache Education and Self-management Study (CHESS) trial dataset., Results: Several models were developed that reasonably accurately predict health utilities in this context. The best performing model for predicting EQ-5D-5L utility scores from the HIT-6 scores was a Censored Least Absolute Deviations (CLAD) (1) model that only included the HIT-6 score as the covariate (mean squared error (MSE) 0.0550). The selected model for CH-QLQ to EQ-5D-5L was the CLAD (3) model that included CH-QLQ summary scores, age, and gender, squared terms and interaction terms as covariates (MSE 0.0583). The best performing model for predicting SF-6D utility scores from the HIT-6 scores was the CLAD (2) model that included the HIT-6 score and age and gender as covariates (MSE 0.0102). The selected model for CH-QLQ to SF-6D was the OLS (2) model that included CH-QLQ summary scores, age, and gender as covariates (MSE 0.0086)., Conclusion: The developed algorithms enable the estimation of EQ-5D-5L and SF-6D utilities from two headache-specific questionnaires where preference-based health-related quality of life data are missing. However, further work is needed to help define the best approach to measuring health utilities in headache studies., (© 2022. The Author(s).)

Background: Preterm birth is associated with adverse health and developmental sequelae that impose a burden on finite resources and significant challenges for individuals, families and societies., Objectives: To estimate economic outcomes at age 11 associated with extremely preterm birth using evidence from a whole population study (EPICure2 study)., Methods: The study population comprised a sample of children born at ≤26 completed weeks of gestation during 2006 in England (n = 200) and a comparison group of classmates born at term (n = 143). Societal costs were estimated using parent and teacher reports of service utilisation, and valuations of work losses and additional care costs to families. Utility scores for the Health Utilities Index Mark 2 (HUI2) and Mark 3 (HUI3) were generated using UK and Canadian value sets. Generalised linear regression was used to estimate the impact of extremely preterm birth on societal costs and utility scores., Results: Unadjusted mean societal costs that excluded provision of special educational support in mainstream schools during the 11th year after birth were £6536 for the extremely preterm group and £3275 for their classmates, generating a difference of £3262 (95% confidence interval [CI] £1912, £5543). The mean adjusted cost difference was £2916 (95% CI £1609, £4224), including special educational needs provision in mainstream schools increased the adjusted cost difference to £4772 (95% CI £3166, £6378). Compared with birth at term, extremely preterm birth generated mean-adjusted utility decrements ranging from 0.13 (95% CI 0.09, 0.18) based on the UK HUI2 statistical inference tariff to 0.28 (95% CI 0.18, 0.37) based on the Canadian HUI3 tariff., Conclusions: The adverse economic impact of extremely preterm birth persists into late childhood. Further longitudinal studies conducted from multiple perspectives are needed to understand the magnitude, trajectory and underpinning mechanisms of economic outcomes following extremely preterm birth., (© 2022 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.)

Introduction: This study sought to identify the availability of automated external defibrillators (AEDs) in schools in the region served by West Midlands Ambulance Service University NHS Trust (WMAS), United Kingdom, and the number of out-of-hospital cardiac arrests (OHCA) that occurred at or near to schools. A secondary aim was to explore the cost effectiveness of school-based defibrillators., Methods: This observational study used data from the national registry for OHCA (University of Warwick) to identify cases occurring at or near schools between January 2014 and December 2016 in WMAS region (n = 11,399). A school survey (n = 2,453) was carried out in September 2017 to determine the presence of AEDs and their registration status with WMAS. Geographical Information System mapping software identified OHCAs occurring within a 300-metre radius of a school. An economic analysis calculated the cost effectiveness of school-based AEDs., Results: A total of 39 (0.34%) of all OHCAs occurred in schools, although 4,250 (37.3%) of OHCAs in the region were estimated to have occurred within 300 metres of a school. Of 323 school survey responses, 184 (57%) had an AED present, of which 24 (13.0%) were available 24 h/day. Economic modelling of a school-based AED programme showed additional quality-adjusted life years (QALY) of 0.26 over the lifetime of cardiac arrest survivors compared with no AED programme. The incremental cost-effectiveness ratio (ICER) was £8,916 per QALY gained., Conclusion: Cardiac arrests in schools are rare. Registering AEDs with local Emergency Medical Services and improving their accessibility within their local community would increase their utility., (© 2022 The Author(s).)

Background: Femoroacetabular impingement syndrome is an important cause of hip pain in young adults. It can be treated by arthroscopic hip surgery or with physiotherapist-led conservative care., Objective: To compare the clinical effectiveness and cost-effectiveness of hip arthroscopy with best conservative care., Design: The UK FASHIoN (full trial of arthroscopic surgery for hip impingement compared with non-operative care) trial was a pragmatic, multicentre, randomised controlled trial that was carried out at 23 NHS hospitals., Participants: Participants were included if they had femoroacetabular impingement, were aged ≥ 16 years old, had hip pain with radiographic features of cam or pincer morphology (but no osteoarthritis) and were believed to be likely to benefit from hip arthroscopy., Intervention: Participants were randomly allocated (1 : 1) to receive hip arthroscopy followed by postoperative physiotherapy, or personalised hip therapy (i.e. an individualised physiotherapist-led programme of conservative care). Randomisation was stratified by impingement type and recruiting centre using a central telephone randomisation service. Outcome assessment and analysis were masked., Main Outcome Measure: The primary outcome was hip-related quality of life, measured by the patient-reported International Hip Outcome Tool (iHOT-33) 12 months after randomisation, and analysed by intention to treat., Results: Between July 2012 and July 2016, 648 eligible patients were identified and 348 participants were recruited. In total, 171 participants were allocated to receive hip arthroscopy and 177 participants were allocated to receive personalised hip therapy. Three further patients were excluded from the trial after randomisation because they did not meet the eligibility criteria. Follow-up at the primary outcome assessment was 92% ( N  = 319; hip arthroscopy, n  = 157; personalised hip therapy, n  = 162). At 12 months, mean International Hip Outcome Tool (iHOT-33) score had improved from 39.2 (standard deviation 20.9) points to 58.8 (standard deviation 27.2) points for participants in the hip arthroscopy group, and from 35.6 (standard deviation 18.2) points to 49.7 (standard deviation 25.5) points for participants in personalised hip therapy group. In the primary analysis, the mean difference in International Hip Outcome Tool scores, adjusted for impingement type, sex, baseline International Hip Outcome Tool score and centre, was 6.8 (95% confidence interval 1.7 to 12.0) points in favour of hip arthroscopy ( p  = 0.0093). This estimate of treatment effect exceeded the minimum clinically important difference (6.1 points). Five (83%) of six serious adverse events in the hip arthroscopy group were related to treatment and one serious adverse event in the personalised hip therapy group was not. Thirty-eight (24%) personalised hip therapy patients chose to have hip arthroscopy between 1 and 3 years after randomisation. Nineteen (12%) hip arthroscopy patients had a revision arthroscopy. Eleven (7%) personalised hip therapy patients and three (2%) hip arthroscopy patients had a hip replacement within 3 years., Limitations: Study participants and treating clinicians were not blinded to the intervention arm. Delays were encountered in participants accessing treatment, particularly surgery. Follow-up lasted for 3 years., Conclusion: Hip arthroscopy and personalised hip therapy both improved hip-related quality of life for patients with femoroacetabular impingement syndrome. Hip arthroscopy led to a greater improvement in quality of life than personalised hip therapy, and this difference was clinically significant at 12 months. This study does not demonstrate cost-effectiveness of hip arthroscopy compared with personalised hip therapy within the first 12 months. Further follow-up will reveal whether or not the clinical benefits of hip arthroscopy are maintained and whether or not it is cost-effective in the long term., Trial Registration: Current Controlled Trials ISRCTN64081839., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 26, No. 16. See the NIHR Journals Library website for further project information.

This single-centre observational study demonstrated that lower cycle threshold (Ct) values (indicating higher viral loads) on admission to hospital were associated with poorer outcomes in unvaccinated, hospitalized patients with coronavirus disease 2019 (COVID-19). Demographic and outcome data were collected prospectively for all adult patients who tested positive for severe acute respiratory syndrome coronavirus-2 on admission to the University Hospitals North Midlands NHS Trust between 1 February and 1 July 2020. Nasopharyngeal swab samples were obtained, and a valid Ct value was determined for all patients using the Viasure reverse transcription polymerase chain reaction assay, validated by Public Health England, on admission to hospital. Multi-variable logistic regression results based on data from 618 individuals demonstrated a significant inverse relationship between the odds of death and Ct values (adjusted odds ratio 0.95, 95% confidence interval 0.92-0.98, P=0.001). The association remained highly significant after adjusting for known clinical risk factors for COVID-19., Competing Interests: Conflict of interest statement None declared., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To compare the quality and acceptability of a new headache-specific patient-reported measure, the Chronic Headache Quality of Life Questionnaire (CHQLQ) with the six-item Headache Impact Test (HIT-6), in people meeting an epidemiological definition of chronic headaches., Methods: Participants in the feasibility stage of the Chronic Headache Education and Self-management Study (CHESS) (n = 130) completed measures three times during a 12-week prospective cohort study. Data quality, measurement acceptability, reliability, validity, responsiveness to change, and score interpretation were determined. Semi-structured cognitive interviews explored measurement relevance, acceptability, clarity, and comprehensiveness., Results: Both measures were well completed with few missing items. The CHQLQ's inclusion of emotional wellbeing items increased its relevance to participant's experience of chronic headache. End effects were present at item level only for both measures. Structural assessment supported the three and one-factor solutions of the CHQLQ and HIT-6, respectively. Both the CHQLQ (range 0.87 to 0.94) and HIT-6 (0.90) were internally consistent, with acceptable temporal stability over 2 weeks (CHQLQ range 0.74 to 0.80; HIT-6 0.86). Both measures responded to change in headache-specific health at 12 weeks (CHQLQ smallest detectable change (improvement) range 3 to 5; HIT-6 2.1)., Conclusions: While both measures are structurally valid, internally consistent, temporally stable, and responsive to change, the CHQLQ has greater relevance to the patient experience of chronic headache. Trial registration number: ISRCTN79708100. Registered 16th December 2015, http://www.isrctn.com/ISRCTN79708100.

Economic evaluations conducted alongside randomized controlled trials are a popular vehicle for generating high-quality evidence on the incremental cost-effectiveness of competing health care interventions. Typically, in these studies, resource use (and by extension, economic costs) and clinical (or preference-based health) outcomes data are collected prospectively for trial participants to estimate the joint distribution of incremental costs and incremental benefits associated with the intervention. In this article, we extend the generalized linear mixed-model framework to enable simultaneous modeling of multiple outcomes of mixed data types, such as those typically encountered in trial-based economic evaluations, taking into account correlation of outcomes due to repeated measurements on the same individual and other clustering effects. We provide new wrapper functions to estimate the models in Stata and R by maximum and restricted maximum quasi-likelihood and compare the performance of the new routines with alternative implementations across a range of statistical programming packages. Empirical applications using observed and simulated data from clinical trials suggest that the new methods produce broadly similar results as compared with Stata's merlin and gsem commands and a Bayesian implementation in WinBUGS. We highlight that, although these empirical applications primarily focus on trial-based economic evaluations, the new methods presented can be generalized to other health economic investigations characterized by multivariate hierarchical data structures.

Background: Adrenaline has been used as a treatment for cardiac arrest for many years, despite uncertainty about its effects on long-term outcomes and concerns that it may cause worse neurological outcomes., Objectives: The objectives were to evaluate the effects of adrenaline on survival and neurological outcomes, and to assess the cost-effectiveness of adrenaline use., Design: This was a pragmatic, randomised, allocation-concealed, placebo-controlled, parallel-group superiority trial and economic evaluation. Costs are expressed in Great British pounds and reported in 2016/17 prices., Setting: This trial was set in five NHS ambulance services in England and Wales., Participants: Adults treated for an out-of-hospital cardiac arrest were included. Patients were ineligible if they were pregnant, if they were aged < 16 years, if the cardiac arrest had been caused by anaphylaxis or life-threatening asthma, or if adrenaline had already been given., Interventions: Participants were randomised to either adrenaline (1 mg) or placebo in a 1 : 1 allocation ratio by the opening of allocation-concealed treatment packs., Main Outcome Measures: The primary outcome was survival to 30 days. The secondary outcomes were survival to hospital admission, survival to hospital discharge, survival at 3, 6 and 12 months, neurological outcomes and health-related quality of life through to 6 months. The economic evaluation assessed the incremental cost per quality-adjusted life-year gained from the perspective of the NHS and Personal Social Services. Participants, clinical teams and those assessing patient outcomes were masked to the treatment allocation., Results: From December 2014 to October 2017, 8014 participants were assigned to the adrenaline ( n  = 4015) or to the placebo ( n  = 3999) arm. At 30 days, 130 out of 4012 participants (3.2%) in the adrenaline arm and 94 out of 3995 (2.4%) in the placebo arm were alive (adjusted odds ratio for survival 1.47, 95% confidence interval 1.09 to 1.97). For secondary outcomes, survival to hospital admission was higher for those receiving adrenaline than for those receiving placebo (23.6% vs. 8.0%; adjusted odds ratio 3.83, 95% confidence interval 3.30 to 4.43). The rate of favourable neurological outcome at hospital discharge was not significantly different between the arms (2.2% vs. 1.9%; adjusted odds ratio 1.19, 95% confidence interval 0.85 to 1.68). The pattern of improved survival but no significant improvement in neurological outcomes continued through to 6 months. By 12 months, survival in the adrenaline arm was 2.7%, compared with 2.0% in the placebo arm (adjusted odds ratio 1.38, 95% confidence interval 1.00 to 1.92). An adjusted subgroup analysis did not identify significant interactions. The incremental cost-effectiveness ratio for adrenaline was estimated at £1,693,003 per quality-adjusted life-year gained over the first 6 months after the cardiac arrest event and £81,070 per quality-adjusted life-year gained over the lifetime of survivors. Additional economic analyses estimated incremental cost-effectiveness ratios for adrenaline at £982,880 per percentage point increase in overall survival and £377,232 per percentage point increase in neurological outcomes over the first 6 months after the cardiac arrest., Limitations: The estimate for survival with a favourable neurological outcome is imprecise because of the small numbers of patients surviving with a good outcome., Conclusions: Adrenaline improved long-term survival, but there was no evidence that it significantly improved neurological outcomes. The incremental cost-effectiveness ratio per quality-adjusted life-year exceeds the threshold of £20,000-30,000 per quality-adjusted life-year usually supported by the NHS., Future Work: Further research is required to better understand patients' preferences in relation to survival and neurological outcomes after out-of-hospital cardiac arrest and to aid interpretation of the trial findings from a patient and public perspective., Trial Registration: Current Controlled Trials ISRCTN73485024 and EudraCT 2014-000792-11., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 25, No. 25. See the NIHR Journals Library website for further project information.

Background: The 'Prehospital Assessment of the Role of Adrenaline: Measuring the Effectiveness of Drug Administration In Cardiac Arrest' (PARAMEDIC2) trial showed that adrenaline improves overall survival, but not neurological outcomes. We sought to determine the within-trial and lifetime health and social care costs and benefits associated with adrenaline, including secondary benefits from organ donation., Methods: We estimated the costs, benefits (quality-adjusted life years (QALYs)) and incremental cost-effectiveness ratios (ICERs) associated with adrenaline during the 6-month trial follow-up. Model-based analyses explored how results altered when the time horizon was extended beyond 6 months and the scope extended to include recipients of donated organs., Results: The within-trial (6 months) and lifetime horizon economic evaluations focussed on the trial population produced ICERs of £1,693,003 (€1,946,953) and £81,070 (€93,231) per QALY gained in 2017 prices, respectively, reflecting significantly higher mean costs and only marginally higher mean QALYs in the adrenaline group. The probability that adrenaline is cost-effective was less than 1% across a range of cost-effectiveness thresholds. Combined direct economic effects over the lifetimes of survivors and indirect economic effects in organ recipients produced an ICER of £16,086 (€18,499) per QALY gained for adrenaline with the probability that adrenaline is cost-effective increasing to 90% at a £30,000 (€34,500) per QALY cost-effectiveness threshold., Conclusions: Adrenaline was not cost-effective when only directly related costs and consequences are considered. However, incorporating the indirect economic effects associated with transplanted organs substantially alters cost-effectiveness, suggesting decision-makers should consider the complexity of direct and indirect economic impacts of adrenaline., Trial Registration: ISRCTN73485024 . Registered on 13 March 2014.

An amendment to this paper has been published and can be accessed via the original article.

Introduction: Chronic headaches are poorly diagnosed and managed and can be exacerbated by medication overuse. There is insufficient evidence on the non-pharmacological approaches to helping people living with chronic headaches., Methods and Analysis: Chronic Headache Education and Self-management Study is a pragmatic randomised controlled trial to test the effectiveness and cost-effectiveness of a self-management education support programme on top of usual care for patients with chronic headaches against a control of usual care and relaxation. The intervention is a 2-day group course based on education, personal reflection and a cognitive behavioural approach, plus a nurse-led one-to-one consultation and follow-up over 8 weeks. We aim to recruit 689 participants (356 to the intervention arm and 333 to the control) from primary care and self-referral in London and the Midlands. The trial is powered to show a difference of 2.0 points on the Headache Impact Test, a patient-reported outcome measure at 12 months post randomisation. Secondary outcomes include health related quality of life, self-efficacy, social activation and engagement, anxiety and depression and healthcare utilisation. Outcomes are being measured at 4, 8 and 12 months. Cost-effectiveness will be expressed in terms of incremental cost per quality-adjusted life year gained., Ethics and Dissemination: This trial will provide data on effectiveness and cost-effectiveness of a self-management support programme for chronic headaches. The results will inform commissioning of services and clinical practice. North West - Greater Manchester East Research Ethics Committee have approved the trial. The current protocol version is 3.6 date 7 March 2019., Trial Registration Number: ISRCTN79708100., Competing Interests: Competing interests: MU is a director and shareholder of Clinvivo Ltd. Use of this company was specified in original application for funding to NIHR. MU has recused himself from all discussion regarding the use of the app in this study. All contracting processes have been in accord with University of Warwick financial regulations. MU was chair of the National Institute for Health and Care Excellence accreditation advisory committee until March 2017 for which he received a fee. He is chief investigator or coinvestigator on multiple previous and current research grants from the UK NIHR, Arthritis Research UK and is a coinvestigator on grants funded by Arthritis Australia and Australian NHMRC. He has received travel expenses for speaking at conferences from the professional organisations hosting the conferences. He is part of an academic partnership with Serco Ltd related to return to work initiatives. He is an editor of the NIHR journal series and a member of the NIHR Journal Editors group for which he receives a fee. He has published multiple papers on chronic pain some of which are referenced in this paper. MM serves on the advisory board for Allergan, Medtronic, Novartis and TEVA and has received payment for the development of educational presentations from Allergan, electroCore, Medtronic, Novartis and TEVA. ShP and HKS are directors of Health Psychology Services Ltd, which in part provides psychological treatments for those with chronic pain., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Spatial weight matrices play a key role in econometrics to capture spatial effects. However, these constructs are prone to clustering and can be challenging to analyse in common statistical packages such as STATA. Multiple observations of survey participants in the same location (or cluster) have traditionally not been dealt with appropriately by statistical packages. It is common that participants are assigned Geographic Information System (GIS) data at a regional or district level rather than at a small area level. For example, the Demographic Health Survey (DHS) generates GIS data at a cluster level, such as a regional or district level, rather than providing coordinates for each participant. Moreover, current statistical packages are not suitable for estimating large matrices such as 20,000 × 20,000 (reflective of data within large health surveys) since the statistical package limits the N to a smaller number. In addition, in many cases, GIS information is offered at an aggregated level of geographical areas. To alleviate this problem, this paper proposes a bootstrap approach that generates an inverse distance spatial weight matrix for application in econometric analyses of health survey data. The new approach is illustrated using DHS data on uptake of HIV testing in low and middle income countries.

Background: Cardiopulmonary resuscitation of cardiac arrest has poor outcomes. Extracorporeal life support (ECLS) could represent a salvage option. This study aimed to analyze the outcomes of ECLS used for refractory cardiac arrest., Methods: In this observational analysis, patients were divided into an in-hospital cardiac arrest group (IHCA) and an out-of-hospital (OHCA) cardiac arrest group. The primary end point was survival to hospital discharge with good neurologic outcome. Both groups were compared after propensity score matching. Risk factors were searched with multivariate analyses., Results: From January 2007 to December 2016, study investigators performed 131 ECLS procedures (IHCA, n = 45, 34.4%; OHCA, n = 86, 65.6%). The mean age of patients was 43.2 years, and 71.8% were male. Baseline characteristics were comparable between both groups except mean no-flow duration (0.2 minutes vs 2.5 minutes; p < 0.001) and low-flow duration (46.9 minutes vs 85.3 minutes; p < 0.001), which were significantly shorter in the IHCA group. A total of 103 (82.4%) patients died during ECLS (IHCA, 79.1% vs OHCA, 84.1%; p = 0.479). The complication rate during ECLS was comparable between both groups. Twenty (16%) patients were successfully weaned from ECLS (IHCA, 18.6% vs OHCA, 14.6%; p = 0.565) after a mean support period of 6.7 days. Survival to hospital discharge with good neurologic outcome was not different between the two matched groups (odds ratio OHCA vs IHCA 1.3; 95% confidence interval, 0.023 to 74.902; p = 0.9). Presence of shockable rhythm was associated with a better outcome (odds ratio shockable vs nonshockable 6.674; 95% confidence interval, 1.078 to 41.336; p = 0.044)., Conclusions: Patients in the IHCA and OHCA groups experienced the same survival with good neurologic outcome after ECLS support. A better selection of patients with IHCA is mandatory to avoid futile support., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: Overprescribing of antibiotics by general practitioners (GPs) is seen as a major driver of antibiotic resistance. Training in communication skills and C-reactive protein (CRP) testing both appear effective in reducing such prescribing. This study assesses the cost-effectiveness (compared with usual care) of: (i) training GPs in the use of CRP testing; (ii) training GPs in communication skills; and (iii) training GPs in both CRP testing and communication skills., Methods: Economic analyses [cost-utility analysis (CUA) accounting for the cost of antibiotic resistance and cost-effectiveness analysis (CEA)] were both conducted from a healthcare perspective with a time horizon of 28 days alongside a multinational, cluster, randomized, factorial controlled trial in patients with respiratory tract infections in five European countries. The primary outcome measures were QALYs and percentage reduction in antibiotic prescribing. Hierarchical modelling was used to estimate an incremental cost per QALY gained and an incremental cost per percentage reduction in antibiotic prescribing., Results: Overall, the results of both the CUA and CEA showed that training in communication skills is the most cost-effective option. However, excluding the cost of antibiotic resistance in the CUA resulted in usual care being the most cost-effective option. Country-specific results from the CUA showed that training in communication skills was cost-effective in Belgium, UK and Netherlands whilst training in CRP was cost-effective in Poland., Conclusions: Internet-based training in communication skills is a cost-effective intervention to reduce antibiotic prescribing for respiratory tract infections in primary care if the cost of antibiotic resistance is accounted for.

Background: Femoroacetabular impingement syndrome is an important cause of hip pain in young adults. It can be treated by arthroscopic hip surgery, including reshaping the hip, or with physiotherapist-led conservative care. We aimed to compare the clinical effectiveness of hip arthroscopy with best conservative care., Methods: UK FASHIoN is a pragmatic, multicentre, assessor-blinded randomised controlled trial, done at 23 National Health Service hospitals in the UK. We enrolled patients with femoroacetabular impingement syndrome who presented at these hospitals. Eligible patients were at least 16 years old, had hip pain with radiographic features of cam or pincer morphology but no osteoarthritis, and were believed to be likely to benefit from hip arthroscopy. Patients with bilateral femoroacetabular impingement syndrome were eligible; only the most symptomatic hip was randomly assigned to treatment and followed-up. Participants were randomly allocated (1:1) to receive hip arthroscopy or personalised hip therapy (an individualised, supervised, and progressive physiotherapist-led programme of conservative care). Randomisation was stratified by impingement type and recruiting centre and was done by research staff at each hospital, using a central telephone randomisation service. Patients and treating clinicians were not masked to treatment allocation, but researchers who collected the outcome assessments and analysed the results were masked. The primary outcome was hip-related quality of life, as measured by the patient-reported International Hip Outcome Tool (iHOT-33) 12 months after randomisation, and analysed in all eligible participants who were allocated to treatment (the intention-to-treat population). This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN64081839, and is closed to recruitment., Findings: Between July 20, 2012, and July 15, 2016, we identified 648 eligible patients and recruited 348 participants: 171 participants were allocated to receive hip arthroscopy and 177 to receive personalised hip therapy. Three further patients were excluded from the trial after randomisation because they did not meet the eligibility criteria. Follow-up at the primary outcome assessment was 92% (319 of 348 participants). At 12 months after randomisation, mean iHOT-33 scores had improved from 39·2 (SD 20·9) to 58·8 (27·2) for participants in the hip arthroscopy group, and from 35·6 (18·2) to 49·7 (25·5) in the personalised hip therapy group. In the primary analysis, the mean difference in iHOT-33 scores, adjusted for impingement type, sex, baseline iHOT-33 score, and centre, was 6·8 (95% CI 1·7-12·0) in favour of hip arthroscopy (p=0·0093). This estimate of treatment effect exceeded the minimum clinically important difference (6·1 points). There were 147 patient-reported adverse events (in 100 [72%] of 138 patients) in the hip arthroscopy group) versus 102 events (in 88 [60%] of 146 patients) in the personalised hip therapy group, with muscle soreness being the most common of these (58 [42%] vs 69 [47%]). There were seven serious adverse events reported by participating hospitals. Five (83%) of six serious adverse events in the hip arthroscopy group were related to treatment, and the one in the personalised hip therapy group was not. There were no treatment-related deaths, but one patient in the hip arthroscopy group developed a hip joint infection after surgery., Interpretation: Hip arthroscopy and personalised hip therapy both improved hip-related quality of life for patients with femoroacetabular impingement syndrome. Hip arthroscopy led to a greater improvement than did personalised hip therapy, and this difference was clinically significant. Further follow-up will reveal whether the clinical benefits of hip arthroscopy are maintained and whether it is cost effective in the long term., Funding: The Health Technology Assessment Programme of the National Institute of Health Research., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Cardiac arrest effectiveness trials have traditionally reported outcomes that focus on survival. A lack of consistency in outcome reporting between trials limits the opportunities to pool results for meta-analysis. The COSCA initiative (Core Outcome Set for Cardiac Arrest), a partnership between patients, their partners, clinicians, research scientists, and the International Liaison Committee on Resuscitation, sought to develop a consensus core outcome set for cardiac arrest for effectiveness trials. Core outcome sets are primarily intended for large, randomised clinical effectiveness trials (sometimes referred to as pragmatic trials or phase III/IV trials) rather than for pilot or efficacy studies. A systematic review of the literature combined with qualitative interviews among cardiac arrest survivors was used to generate a list of potential outcome domains. This list was prioritised through a Delphi process, which involved clinicians, patients, and their relatives/partners. An international advisory panel narrowed these down to 3 core domains by debate that led to consensus. The writing group refined recommendations for when these outcomes should be measured and further characterised relevant measurement tools. Consensus emerged that a core outcome set for reporting on effectiveness studies of cardiac arrest (COSCA) in adults should include survival, neurological function, and health-related quality of life. This should be reported as survival status and modified Rankin scale score at hospital discharge, at 30 days, or both. Health-related quality of life should be measured with ≥1 tools from Health Utilities Index version 3, Short-Form 36-Item Health Survey, and EuroQol 5D-5L at 90 days and at periodic intervals up to 1 year after cardiac arrest, if resources allow. © 2018 European Resuscitation Council and American Heart Association, Inc. Published by Elsevier B.V. All rights reserved., (Copyright © 2018 European Resuscitation Council and American Heart Association, Inc. Published by Elsevier B.V. All rights reserved.)