Comparative cost-effectiveness of termination of resuscitation rules for patients transported in cardiac arrest.

AIM: To compare the cost-effectiveness of termination-of-resuscitation (TOR) rules for patients transported in cardiac arrest. METHODS: The economic analyses evaluated cost-effectiveness of alternative TOR rules for OHCA from a National Health Service (NHS) and personal social services (PSS) perspective over a lifetime horizon. A systematic review was used to identify the different TOR rules included in the analyses. Data from the OHCAO outcomes registry, trial data and published literature were used to compare outcomes for the different rules identified. The economic analyses estimated discounted NHS and PSS costs and quality-adjusted life-years (QALYs) for each TOR rule, based on which incremental cost-effectiveness ratios (ICERs) were calculated. RESULTS: The systematic review identified 33 TOR rules and the economic analyses assessed the performance of 29 of these TOR rules plus current practice. The most cost-effective strategies were the European Resuscitation Council (ERC) termination of resuscitation rule (ICER of £8,111), the Korean Cardiac Arrest Research Consortium 2 (KOC 2) termination of resuscitation rule (ICER of £17,548), and the universal Basic Life Support (BLS) termination of resuscitation rule (ICER of £19,498,216). The KOC 2 TOR rule was cost-effective at the established cost-effectiveness threshold of £20,000-£30,000 per QALY. CONCLUSION: The KOC 2 rule is the most cost-effective at established cost-effectiveness thresholds used to inform health care decision-making in the UK. Further research on economic implications of TOR rules is warranted to support constructive discussion on implementing TOR rules.

Functional outcomes and quality of life at 1-year follow-up after an open tibia fracture in Malawi: a multicentre, prospective cohort study.

BACKGROUND: Injuries are a major cause of disability globally and injury incidence is rapidly increasing, largely due to road traffic injuries in low-income and middle-income countries. Current estimates of the scale and consequences of disability from injury are largely based on modelling studies, with a scarcity of empirical evidence from severe injuries in low-income countries. We aimed to better understand the outcomes for individuals with open tibia fractures in Malawi. METHODS: In this multicentre, prospective cohort study, adults (aged ≥18 years) with open tibia fractures were systematically recruited at six hospitals in Malawi (two tertiary hospitals and four district hospitals). Follow-up lasted at least 1 year, during which in-person follow-up reviews were done at 6 weeks, 3 months, 6 months, and 1 year post-injury. The primary outcome was function at 1 year post-injury, measured by the Short Musculoskeletal Functional Assessment (SMFA) score. Secondary outcomes included quality-adjusted life-years (QALYs; as determined via the European Quality of Life 5-Dimensions 3-Levels [EQ-5D-3L] survey) and fracture-related infection at 1 year post-injury. Multilevel regression models investigated associations between SMFA score, EQ-5D-3L, baseline factors, and orthopaedic management. FINDINGS: Between Feb 12, 2021, and March 14, 2022, 287 participants were enrolled (median age 34 years [IQR 25-44]; 84% male). The most common mode of injury was road traffic injuries (194 [68%] of 287). Overall, 268 (93%) participants had debridement; of the 63 participants who were debrided in district hospitals, 47 (75%) had the procedure under local or no anaesthesia. Following substantial declines by 6 weeks after injury, function and quality of life had not recovered by 1 year post-injury for participants with Gustilo grade I-II fractures (posterior mean SMFA at 1 year: 10·5, 95% highest density interval [HDI]: 9·5-11·6; QALYs: 0·73, 95% HDI: 0·66-0·80) nor Gustilo grade III fractures (posterior mean SMFA at 1 year: 14·9, 95% HDI: 13·4-16·6; QALYs: 0·67, 95% HDI: 0·59-0·75). For all fracture grades, intramedullary nailing substantially improved function and quality of life at 1 year post-injury. Delayed definitive fixation after 5 days had 5-times greater odds of infection compared with early management within 2 days (adjusted odds ratio: 5·1, 95% CI 1·8-16·1; p=0·02). INTERPRETATION: Adults with open tibia fractures in Malawi have poor function and quality of life in the 1 year following injury. Centralised orthopaedic surgical management, including early definitive fixation and intramedullary nailing for more severe injuries, might improve outcomes. FUNDING: Wellcome Trust. TRANSLATION: For the Chichewa translation of the abstract see Supplementary Materials section.

Economic evaluation of shortened, bedaquiline-containing treatment regimens for rifampicin-resistant tuberculosis (STREAM stage 2): a within-trial analysis of a randomised controlled trial.

BACKGROUND: The STREAM stage 2 trial assessed two bedaquiline-containing regimens for rifampicin-resistant tuberculosis: a 9-month all-oral regimen and a 6-month regimen containing an injectable drug for the first 2 months. We did a within-trial economic evaluation of these regimens. METHODS: STREAM stage 2 was an international, phase 3, non-inferiority randomised trial in which participants with rifampicin-resistant tuberculosis were randomly assigned (1:2:2:2) to the 2011 WHO regimen (terminated early), a 9-month injectable-containing regimen (control regimen), a 9-month all-oral regimen with bedaquiline (oral regimen), or a 6-month regimen with bedaquiline and an injectable for the first 2 months (6-month regimen). We prospectively collected direct and indirect costs and health-related quality of life data from trial participants until week 76 of follow-up. Cost-effectiveness of the oral and 6-month regimens versus control was estimated in four countries (oral regimen) and two countries (6-month regimen), using health-related quality of life for cost-utility analysis and trial efficacy for cost-effectiveness analysis. This trial is registered with ISRCTN, ISRCTN18148631. FINDINGS: 300 participants were included in the economic analyses (Ethiopia, 61; India, 142; Moldova, 51; Uganda, 46). In the cost-utility analysis, the oral regimen was not cost-effective in Ethiopia, India, Moldova, and Uganda from either a provider or societal perspective. In Moldova, the oral regimen was dominant from a societal perspective. In the cost-effectiveness analysis, the oral regimen was likely to be cost-effective from a provider perspective at willingness-to-pay thresholds per additional favourable outcome of more than US$4500 in Ethiopia, $1900 in India, $3950 in Moldova, and $7900 in Uganda, and from a societal perspective at thresholds of more than $15 900 in Ethiopia, $3150 in India, and $4350 in Uganda, while in Moldova the oral regimen was dominant. In Ethiopia and India, the 6-month regimen would cost tuberculosis programmes and participants less than the control regimen and was highly likely to be cost-effective in both cost-utility analysis and cost-effectiveness analysis. Reducing the bedaquiline price from $1·81 to $1·00 per tablet made the oral regimen cost-effective in the provider-perspective cost-utility analysis in India and Moldova and dominate over the control regimen in the provider-perspective cost-effectiveness analysis in India. INTERPRETATION: At current costs, the oral bedaquiline-containing regimen for rifampicin-resistant tuberculosis is unlikely to be cost-effective in many low-income and middle-income countries. The 6-month regimen represents a cost-effective alternative if injectable use for 2 months is acceptable. FUNDING: USAID and Janssen Research & Development.

TB morbidity estimates overlook the contribution of post-TB disability: evidence from urban Malawi.

INTRODUCTION: Despite growing evidence of the long-term impact of tuberculosis (TB) on quality of life, Global Burden of Disease (GBD) estimates of TB-related disability-adjusted life years (DALYs) do not include post-TB morbidity, and evaluations of TB interventions typically assume treated patients return to pre-TB health. Using primary data, we estimate years of life lost due to disability (YLDs), years of life lost due to premature mortality (YLL) and DALYs associated with post-TB cardiorespiratory morbidity in a low-income country. METHODS: Adults aged ≥15 years who had successfully completed treatment for drug-sensitive pulmonary TB in Blantyre, Malawi (February 2016-April 2017) were followed-up for 3 years with 6-monthly and 12-monthly study visits. In this secondary analysis, St George's Respiratory Questionnaire data were used to match patients to GBD cardiorespiratory health states and corresponding disability weights (DWs) at each visit. YLDs were calculated for the study period and estimated for remaining lifespan using Malawian life table life expectancies. YLL were estimated using study mortality data and aspirational life expectancies, and post-TB DALYs derived. Data were disaggregated by HIV status and gender. RESULTS: At treatment completion, 222/403 (55.1%) participants met criteria for a cardiorespiratory DW, decreasing to 15.6% after 3 years, at which point two-thirds of the disability burden was experienced by women. Over 90% of projected lifetime-YLD were concentrated within the most severely affected 20% of survivors. Mean DWs in the 3 years post-treatment were 0.041 (HIV-) and 0.025 (HIV+), and beyond 3 years estimated as 0.025 (HIV-) and 0.010 (HIV+), compared with GBD DWs of 0.408 (HIV+) and 0.333 (HIV-) during active disease. Our results imply that the majority of TB-related morbidity occurs post-treatment. CONCLUSION: TB-related DALYs are greatly underestimated by overlooking post-TB disability. The total disability burden of TB is likely undervalued by both GBD estimates and economic evaluations of interventions, particularly those aimed at early diagnosis and prevention.

Cost-effectiveness of community health systems strengthening: quality improvement interventions at community level to realise maternal and child health gains in Kenya.

INTRODUCTION: Improvements in maternal and infant health outcomes are policy priorities in Kenya. Achieving these outcomes depends on early identification of pregnancy and quality of primary healthcare. Quality improvement interventions have been shown to contribute to increases in identification, referral and follow-up of pregnant women by community health workers. In this study, we evaluate the cost-effectiveness of using quality improvement at community level to reduce maternal and infant mortality in Kenya. METHODS: We estimated the cost-effectiveness of quality improvement compared with standard of care treatment for antenatal and delivering mothers using a decision tree model and taking a health system perspective. We used both process (antenatal initiation in first trimester and skilled delivery) and health outcomes (maternal and infant deaths averted, as well as disability-adjusted life years (DALYs)) as our effectiveness measures and actual implementation costs, discounting costs only. We conducted deterministic and probabilistic sensitivity analyses. RESULTS: We found that the community quality improvement intervention was more cost-effective compared with standard community healthcare, with incremental cost per DALY averted of $249 under the deterministic analysis and 76% likelihood of cost-effectiveness under the probabilistic sensitivity analysis using a standard threshold. The deterministic estimate of incremental cost per additional skilled delivery was US$10, per additional early antenatal care presentation US$155, per maternal death averted US$5654 and per infant death averted US$37 536 (2017 dollars). CONCLUSIONS: This analysis shows that the community quality improvement intervention was cost-effective compared with the standard community healthcare in Kenya due to improvements in antenatal care uptake and skilled delivery. It is likely that quality improvement interventions are a good investment and may also yield benefits in other health areas.

Protocol for a prospective cohort study of open tibia fractures in Malawi with a nested implementation of open fracture guidelines.

Background: Road traffic injury (RTI) is the largest cause of death amongst 15-39-year-old people worldwide, and the burden of injuries such as open tibia fractures are rapidly increasing in Malawi. This study aims to investigate disability and economic outcomes of people with open tibia fractures in Malawi and improve these with locally delivered implementation of open fracture guidelines. Methods: This is a prospective cohort study describing function, quality of life and economic burden of open tibia fractures in Malawi. In total, 160 participants will be recruited across six centres and will be followed-up with face-to-face interviews at six weeks, three months, six months and one year following injury. The primary outcome will be function at one year measured by the short musculoskeletal functional assessment (SMFA) score. Secondary outcomes will include quality of life measured by EuroQol EQ-5D-3L, catastrophic loss of income and implementation outcomes (acceptability, adoption, appropriateness, costs, feasibility, fidelity, penetration, and sustainability) at one year. A nested pilot pre-post implementation study of an interventional bundle for all open fractures will be developed based on other implementation studies from low- and middle-income countries (LMICs). Regression analysis will be used to model and investigate associations between SMFA score and fracture severity, infection and the pre- and post-training course period. Outcome: This prospective cohort study will report patient reported outcomes from open tibia fractures in low-resource settings. Subsequent detailed evaluation of both the clinical and implementation components of the study will promote sustainability of improved open fractures management in the study sites and further scale-up of open fracture management guidelines. Ethics: Ethics approval has been obtained from the Liverpool School of Tropical Medicine and College of Medicine Research and Ethics committee.

Impact of the societal response to COVID-19 on access to healthcare for non-COVID-19 health issues in slum communities of Bangladesh, Kenya, Nigeria and Pakistan: results of pre-COVID and COVID-19 lockdown stakeholder engagements.

INTRODUCTION: With COVID-19, there is urgency for policymakers to understand and respond to the health needs of slum communities. Lockdowns for pandemic control have health, social and economic consequences. We consider access to healthcare before and during COVID-19 with those working and living in slum communities. METHODS: In seven slums in Bangladesh, Kenya, Nigeria and Pakistan, we explored stakeholder perspectives and experiences of healthcare access for non-COVID-19 conditions in two periods: pre-COVID-19 and during COVID-19 lockdowns. RESULTS: Between March 2018 and May 2020, we engaged with 860 community leaders, residents, health workers and local authority representatives. Perceived common illnesses in all sites included respiratory, gastric, waterborne and mosquitoborne illnesses and hypertension. Pre-COVID, stakeholders described various preventive, diagnostic and treatment services, including well-used antenatal and immunisation programmes and some screening for hypertension, tuberculosis, HIV and vectorborne disease. In all sites, pharmacists and patent medicine vendors were key providers of treatment and advice for minor illnesses. Mental health services and those addressing gender-based violence were perceived to be limited or unavailable. With COVID-19, a reduction in access to healthcare services was reported in all sites, including preventive services. Cost of healthcare increased while household income reduced. Residents had difficulty reaching healthcare facilities. Fear of being diagnosed with COVID-19 discouraged healthcare seeking. Alleviators included provision of healthcare by phone, pharmacists/drug vendors extending credit and residents receiving philanthropic or government support; these were inconsistent and inadequate. CONCLUSION: Slum residents' ability to seek healthcare for non-COVID-19 conditions has been reduced during lockdowns. To encourage healthcare seeking, clear communication is needed about what is available and whether infection control is in place. Policymakers need to ensure that costs do not escalate and unfairly disadvantage slum communities. Remote consulting to reduce face-to-face contact and provision of mental health and gender-based violence services should be considered.

Cost-utility analysis of standard dressing compared with incisional negative-pressure wound therapy among patients with closed surgical wounds following major trauma to the lower limb.

AIMS: To compare the cost-utility of standard dressing with incisional negative-pressure wound therapy (iNPWT) in adults with closed surgical wounds associated with major trauma to the lower limbs. METHODS: A within-trial economic evaluation was conducted from the UK NHS and personal social services (PSS) perspective based on data collected from the Wound Healing in Surgery for Trauma (WHiST) multicentre randomized clinical trial. Health resource utilization was collected over a six-month post-randomization period using trial case report forms and participant-completed questionnaires. Cost-utility was reported in terms of incremental cost per quality-adjusted life year (QALY) gained. Sensitivity analysis was conducted to test the robustness of cost-effectiveness estimates while uncertainty was handled using confidence ellipses and cost-effectiveness acceptability curves. RESULTS: The incremental cost of standard dressing versus iNPWT over six months was £2,037 (95% confidence interval (CI) £349 to £3,724). There was an insignificant increment in QALYs gained in the iNPWT group (0.005, 95% CI -0.018 to 0.028). The probability of iNPWT being cost-effective at £20,000 per QALY was 1.9%. The results remained robust in the sensitivity analysis. CONCLUSION: The within-trial economic evaluation suggests that iNPWT is unlikely to be a cost-effective alternative to standard dressing in adults with closed surgical wounds to their lower limbs. Cite this article: Bone Joint J 2020;102-B(8):1072-1081.

Economic evaluation of short treatment for multidrug-resistant tuberculosis, Ethiopia and South Africa: the STREAM trial.

OBJECTIVE: To investigate cost changes for health systems and participants, resulting from switching to short treatment regimens for multidrug-resistant (MDR) tuberculosis. METHODS: We compared the costs to health systems and participants of long (20 to 22 months) and short (9 to 11 months) MDR tuberculosis regimens in Ethiopia and South Africa. Cost data were collected from participants in the STREAM phase-III randomized controlled trial and we estimated health-system costs using bottom-up and top-down approaches. A cost-effectiveness analysis was performed by calculating the incremental cost per unfavourable outcome avoided. FINDINGS: Health-care costs per participant in South Africa were 8340.7 United States dollars (US$) with the long and US$ 6618.0 with the short regimen; in Ethiopia, they were US$ 6096.6 and US$ 4552.3, respectively. The largest component of the saving was medication costs in South Africa (67%; US$ 1157.0 of total US$ 1722.8) and social support costs in Ethiopia (35%, US$ 545.2 of total US$ 1544.3). In Ethiopia, trial participants on the short regimen reported lower expenditure for supplementary food (mean reduction per participant: US$ 225.5) and increased working hours (i.e. 667 additional hours over 132 weeks). The probability that the short regimen was cost-effective was greater than 95% when the value placed on avoiding an unfavourable outcome was less than US$ 19 000 in Ethiopia and less than US$ 14 500 in South Africa. CONCLUSION: The short MDR tuberculosis treatment regimen was associated with a substantial reduction in health-system costs and a lower financial burden for participants.

Is quality affordable for community health systems? Costs of integrating quality improvement into close-to-community health programmes in five low-income and middle-income countries.

INTRODUCTION: Countries aspiring to universal health coverage view close-to-community (CTC) providers as a low-cost means of increasing coverage. However, due to lack of coordination and unreliable funding, the quality of large-scale CTC healthcare provision is highly variable and routine data about service quality are not trustworthy. Quality improvement (QI) approaches are a means of addressing these issues, yet neither the costs nor the budget impact of integrating QI approaches into CTC programme costs have been assessed. METHODS: This paper examines the costs and budget impact of integrating QI into existing CTC health programmes in five countries (Ethiopia, Indonesia, Kenya, Malawi, Mozambique) between 2015 and 2017. The intervention involved: (1) QI team formation; (2) Phased training interspersed with supportive supervision; which resulted in (3) QI teams independently collecting and analysing data to conduct QI interventions. Project costs were collected using an ingredients approach from a health systems perspective. Based on project costs, costs of local adoption of the intervention were modelled under three implementation scenarios. RESULTS: Annualised economic unit costs ranged from $62 in Mozambique to $254 in Ethiopia per CTC provider supervised, driven by the context, type of community health model and the intensity of the intervention. The budget impact of Ministry-led QI for community health is estimated at 0.53% or less of the general government expenditure on health in all countries (and below 0.03% in three of the five countries). CONCLUSION: CTC provision is a key component of healthcare delivery in many settings, so QI has huge potential impact. The impact is difficult to establish conclusively, but as a first step we have provided evidence to assess affordability of QI for community health. Further research is needed to assess whether QI can achieve the level of benefits that would justify the required investment.

Aspirin in venous leg ulcer study (ASPiVLU): study protocol for a randomised controlled trial.

BACKGROUND: Venous leg ulceration is a common and costly problem that is expected to worsen as the population ages. Current treatment is compression therapy; however, up to 50 % of ulcers remain unhealed after 2 years, and ulcer recurrence is common. New treatments are needed to address those wounds that are more challenging to heal. Targeting the inflammatory processes present in venous ulcers is a possible strategy. Limited evidence suggests that a daily dose of aspirin may be an effective adjunct to aid ulcer healing and reduce recurrence. The Aspirin in Venous Leg Ulcer study (ASPiVLU) will investigate whether 300-mg oral doses of aspirin improve time to healing. METHODS/DESIGN: This randomised, double-blinded, multicentre, placebo-controlled, clinical trial will recruit participants with venous leg ulcers from community settings and hospital outpatient wound clinics across Australia. Two hundred sixty-eight participants with venous leg ulcers will be randomised to receive either aspirin or placebo, in addition to compression therapy, for 24 weeks. The primary outcome is time to healing within 12 weeks. Secondary outcomes are ulcer recurrence, wound pain, quality of life and wellbeing, adherence to study medication, adherence to compression therapy, serum inflammatory markers, hospitalisations, and adverse events at 24 weeks. DISCUSSION: The ASPiVLU trial will investigate the efficacy and safety of aspirin as an adjunct to compression therapy to treat venous leg ulcers. Study completion is anticipated to occur in December 2018. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12614000293662.

Improving health outcomes for young people with long term conditions: The role of digital communication in current and future patient-clinician communication for NHS providers of specialist clinical services for young people - LYNC study protocol.

BACKGROUND: Young people living with long term conditions are vulnerable to health service disengagement. This endangers their long term health. Studies report requests for digital forms of communication - email, text, social media - with their health care team. Digital clinical communication is troublesome for the UK NHS. AIM: In this article we aim to present the research protocol for evaluating the impacts and outcomes of digital clinical communications for young people living with long term conditions and provide critical analysis of their use, monitoring and evaluation by NHS providers (LYNC study: Long term conditions, Young people, Networked Communications). METHODS: The research involves: (a) patient and public involvement activities with 16-24 year olds with and without long term health conditions; (b) six literature reviews; (c) case studies - the main empirical part of the study - and (d) synthesis and a consensus meeting. Case studies use a mixed methods design. Interviews and non-participant observation of practitioners and patients communicating in up to 20 specialist clinical settings will be combined with data, aggregated at the case level (non-identifiable patient data) on a range of clinical outcomes meaningful within the case and across cases. We will describe the use of digital clinical communication from the perspective of patients, clinical staff, support staff and managers, interviewing up to 15 young people and 15 staff per case study. Outcome data includes emergency admissions, A&E attendance and DNA (did not attend) rates. Case studies will be analysed to understand impacts of digital clinical communication on patient health outcomes, health care costs and consumption, ethics and patient safety.

Expected value of sample information for multi-arm cluster randomized trials with binary outcomes.

Expected value of sample information (EVSI) measures the anticipated net benefit gained from conducting new research with a specific design to add to the evidence on which reimbursement decisions are made. Cluster randomized trials raise specific issues for EVSI calculations because 1) a hierarchical model is necessary to account for between-cluster variability when incorporating new evidence and 2) heterogeneity between clusters needs to be carefully characterized in the cost-effectiveness analysis model. Multi-arm trials provide parameter estimates that are correlated, which needs to be accounted for in EVSI calculations. Furthermore, EVSI is computationally intensive when the net benefit function is nonlinear, due to the need for an inner-simulation step. We develop a method for the computation of EVSI that avoids the inner simulation step for cluster randomized multi-arm trials with a binary outcome, where the net benefit function is linear in the probability of an event but nonlinear in the log-odds ratio parameters. We motivate and illustrate the method with an example of a cluster randomized 2 × 2 factorial trial for interventions to increase attendance at breast screening in the UK, using a previously reported cost-effectiveness model. We highlight assumptions made in our approach, extensions to individually randomized trials and inclusion of covariates, and areas for further developments. We discuss computation time, the research-design space, and the ethical implications of an EVSI approach. We suggest that EVSI is a practical and appropriate tool for the design of cluster randomized trials.

Which health-related quality-of-life outcome when planning randomized trials: disease-specific or generic, or both? A common factor model.

The primary outcomes in trials are usually disease-specific measures (DSMs) designed to be responsive to changes in the condition caused by treatment. For purposes of cost-effectiveness analysis, treatment effects on the DSM are often "mapped" into treatment effects on a generic health-related quality-of-life (QOL) scale, such as EuroQol five-dimensional questionnaire. Trialists have the option of including generic QOL measures as trial outcomes. We consider the relative efficiency (estimate divided by its standard error) of treatment effects derived from the DSM, the generic QOL, the generic QOL indirectly estimated from the mapped DSM, and a pooled estimate combining the direct and indirect information on the generic QOL. By using a "common factor" theory of the relationship between the DSM and the generic QOL, we define the circumstances under which indirectly estimated generic QOL is more efficient than the direct one and when a pooled QOL estimate is more efficient than the DSM estimate. As long as the DSM is more responsive, there is always a threshold sample size above which the indirect estimate has better precision than the direct estimate. This threshold, however, increases as the (1) relative responsiveness ratio of the DSM to the generic QOL increases, (2) precision of the estimated mapping coefficient increases, and (3) true effect becomes smaller. The pooled estimate on the generic QOL may be more efficient than the DSM itself unless the reliability of the DSM is particularly high. Trials powered on DSMs are likely to have sufficient power to detect treatment effect on the generic QOL if a pooled estimate is used. We conclude that generic QOL instruments should be routinely included in randomized controlled trials. Information on mapping coefficients and on relative responsiveness should be collected more systematically to facilitate both evidence synthesis and trial design.