Cost-effectiveness of single, high-dose, liposomal amphotericin regimen for HIV-associated cryptococcal meningitis in five countries in sub-Saharan Africa: an economic analysis of the AMBITION-cm trial.

BACKGROUND: HIV-associated cryptococcal meningitis is a leading cause of AIDS-related mortality. The AMBITION-cm trial showed that a regimen based on a single high dose of liposomal amphotericin B deoxycholate (AmBisome group) was non-inferior to the WHO-recommended treatment of seven daily doses of amphotericin B deoxycholate (control group) and was associated with fewer adverse events. We present a five-country cost-effectiveness analysis. METHODS: The AMBITION-cm trial enrolled patients with HIV-associated cryptococcal meningitis from eight hospitals in Botswana, Malawi, South Africa, Uganda, and Zimbabwe. Taking a health service perspective, we collected country-specific unit costs and individual resource-use data per participant over the 10-week trial period, calculating mean cost per participant by group, mean cost-difference between groups, and incremental cost-effectiveness ratio per life-year saved. Non-parametric bootstrapping and scenarios analyses were performed including hypothetical real-world resource use. The trial registration number is ISRCTN72509687, and the trial has been completed. FINDINGS: The AMBITION-cm trial enrolled 844 participants, and 814 were included in the intention-to-treat analysis (327 from Uganda, 225 from Malawi, 107 from South Africa, 84 from Botswana, and 71 from Zimbabwe) with 407 in each group, between Jan 31, 2018, and Feb 17, 2021. Using Malawi as a representative example, mean total costs per participant were US$1369 (95% CI 1314-1424) in the AmBisome group and $1237 (1181-1293) in the control group. The incremental cost-effectiveness ratio was $128 (59-257) per life-year saved. Excluding study protocol-driven cost, using a real-world toxicity monitoring schedule, the cost per life-year saved reduced to $80 (15-275). Changes in the duration of the hospital stay and antifungal medication cost showed the greatest effect in sensitivity analyses. Results were similar across countries, with the cost per life-year saved in the real-world scenario ranging from $71 in Botswana to $121 in Uganda. INTERPRETATION: The AmBisome regimen was cost-effective at a low incremental cost-effectiveness ratio. The regimen might be even less costly and potentially cost-saving in real-world implementation given the lower drug-related toxicity and the potential for shorter hospital stays. FUNDING: European Developing Countries Clinical Trials Partnership, Swedish International Development Cooperation Agency, Wellcome Trust and Medical Research Council, UKAID Joint Global Health Trials, and the National Institute for Health Research. TRANSLATIONS: For the Chichewa, Isixhosa, Luganda, Setswana and Shona translations of the abstract see Supplementary Materials section.

Factors Influencing the Efficiency of Public Hospitals in Saudi Arabia: A Qualitative Study Exploring Stakeholders' Perspectives and Suggestions for Improvement.

Objective: Despite an extensive literature on efficiency, qualitative evidence on the drivers of hospital efficiency is scant. This study examined the factors that influence the efficiencies of health service provision in public hospitals in the Kingdom of Saudi Arabia (KSA) and their potential remedies. Design: We employed a qualitative design involving semi-structured interviews conducted between July and September 2019. Participants were purposively selected and included policymakers and hospital managers drawn from districts, regional and national levels. Data were analyzed in Nvivo 12 based on a thematic approach. Setting: Key informants of Ministry of health in the KSA. Results: Respondents identified a range of different factors across the community, facility and the wider health system that influence inefficiencies in public hospitals in KSA. Ineffective hospital management, lack of strategic planning and goals, weak administrative leadership, and absence of monitoring hospital performance was noted to have a profound impact on hospital efficiency. The conditions of healthcare staff in respect to both skills, authority and psychological factors were considered to influence the efficiency level. Further, lack of appropriate data for decision making due to the absence of an appropriate health informatics system was regarded as a factor of inefficiency. At the community level, respondents described inadequate information on the healthcare needs and expectations of patients and the wider community as significant barriers to the provision of efficient services. To improve hospital efficiencies, respondents recommended that service delivery decisions are informed by data on community health needs; capacity strengthening and effective supervision of hospital staff; and judicious resource allocation. Conclusion: The study demonstrates that inefficiencies in health services remain a critical challenge in public hospitals in KSA. Extensive awareness-raising and training on efficient resource utilization among key health systems stakeholders are imperative to improving hospital performance. More research is needed to strengthen knowledge on hospital efficiency in light of the limited data on the topic in KSA and the wider Gulf region.

Household Microenvironment and Under-Fives Health Outcomes in Uganda: Focusing on Multidimensional Energy Poverty and Women Empowerment Indices.

Young children in low- and middle-income countries (LMICs) are vulnerable to adverse effects of household microenvironments. The UN Sustainable Development Goals (SDGs)-specifically SDG 3 through 7-urge for a comprehensive multi-sector approach to achieve the 2030 goals. This study addresses gaps in understanding the health effects of household microenvironments in resource-poor settings. It studies associations of household microenvironment variables with episodes of acute respiratory infection (ARI) and diarrhoea as well as with stunting among under-fives using logistic regression. Comprehensive data from a nationally representative, cross-sectional demographic and health survey (DHS) in Uganda were analysed. We constructed and applied the multidimensional energy poverty index (MEPI) and the three-dimensional women empowerment index in multi-variate regressions. The multidimensional energy poverty was associated with higher risk of ARI (OR = 1.32, 95% CI 1.10 to 1.58). Social independence of women was associated with lower risk of ARI (OR= 0.91, 95% CI 0.84 to 0.98), diarrhoea (OR = 0.93, 95% CI 0.88 to 0.99), and stunting (OR = 0.83, 95% CI 0.75 to 0.92). Women's attitude against domestic violence was also significantly associated with episodes of ARI (OR = 0.88, 95% CI 0.82 to 0.93) and diarrhoea (OR = 0.89, 95% CI 0.84 to 0.93) in children. Access to sanitation facilities was associated with lower risk of ARI (OR = 0.55, 95% CI 0.45 to 0.68), diarrhoea (OR = 0.83, 95% CI 0.71 to 0.96), and stunting (OR = 0.64, 95% CI 0.49 to 0.86). Investments targeting synergies in integrated energy and water, sanitation and hygiene, and women empowerment programmes are likely to contribute to the reduction of the burden from early childhood illnesses. Research and development actions in LMICs should address and include multi-sector synergies.

Assessing the incidence of catastrophic health expenditure and impoverishment from out-of-pocket payments and their determinants in Bangladesh: evidence from the nationwide Household Income and Expenditure Survey 2016.

BACKGROUND: Out-of-pocket (OOP) payments for healthcare have been increasing steadily in Bangladesh, which deteriorates the financial risk protection of many households. METHODS: We aimed to investigate the incidence of catastrophic health expenditure (CHE) and impoverishment from OOP payments and their determinants. We employed nationally representative Household Income and Expenditure Survey 2016 data with a sample of 46 076 households. A household that made OOP payments of >10% of its total or 40% of its non-food expenditure was considered to be facing CHE. We estimated the impoverishment using both national and international poverty lines. Multiple logistic models were employed to identify the determinants of CHE and impoverishment. RESULTS: The incidence of CHE was estimated as 24.6% and 10.9% using 10% of the total and 40% of non-food expenditure as thresholds, respectively, and these were concentrated among the poor. About 4.5% of the population (8.61 million) fell into poverty during 2016. Utilization of private facilities, the presence of older people, chronic illness and geographical location were the main determinants of both CHE and impoverishment. CONCLUSION: The financial hardship due to OOP payments was high and it should be reduced by regulating the private health sector and covering the care of older people and chronic illness by prepayment-financing mechanisms.

Palliative care and catastrophic costs in Malawi after a diagnosis of advanced cancer: a prospective cohort study.

BACKGROUND: Inclusive universal health coverage requires access to quality health care without financial barriers. Receipt of palliative care after advanced cancer diagnosis might reduce household poverty, but evidence from low-income and middle-income settings is sparse. METHODS: In this prospective study, the primary objective was to investigate total household costs of cancer-related health care after a diagnosis of advanced cancer, with and without the receipt of palliative care. Households comprising patients and their unpaid family caregiver were recruited into a cohort study at Queen Elizabeth Central Hospital in Malawi, between Jan 16 and July 31, 2019. Costs of cancer-related health-care use (including palliative care) and health-related quality-of-life were recorded over 6 months. Regression analysis explored associations between receipt of palliative care and total household costs on health care as a proportion of household income. Catastrophic costs, defined as 20% or more of total household income, sale of assets and loans taken out (dissaving), and their association with palliative care were computed. FINDINGS: We recruited 150 households. At 6 months, data from 89 (59%) of 150 households were available, comprising 89 patients (median age 50 years, 79% female) and 64 caregivers (median age 40 years, 73% female). Patients in 55 (37%) of the 150 households died and six (4%) were lost to follow-up. 19 (21%) of 89 households received palliative care. Catastrophic costs were experienced by nine (47%) of 19 households who received palliative care versus 48 (69%) of 70 households who did not (relative risk 0·69, 95% CI 0·42 to 1·14, p=0·109). Palliative care was associated with substantially reduced dissaving (median US$11, IQR 0 to 30 vs $34, 14 to 75; p=0·005). The mean difference in total household costs on cancer-related health care with receipt of palliative care was -36% (95% CI -94 to 594; p=0·707). INTERPRETATION: Vulnerable households in low-income countries are subject to catastrophic health-related costs following a diagnosis of advanced cancer. Palliative care might result in reduced dissaving in these households. Further consideration of the economic benefits of palliative care is justified. FUNDING: Wellcome Trust; National Institute for Health Research; and EMMS International.

Changing lung function and associated health-related quality-of-life: A five-year cohort study of Malawian adults.

BACKGROUND: In Sub-Saharan Africa cross-sectional studies report a high prevalence of abnormal lung function indicative of chronic respiratory disease. The natural history and health impact of this abnormal lung function in low-and middle-income countries is largely unknown. METHODS: A cohort of 1481 adults representative of rural Chikwawa in Malawi were recruited in 2014 and followed-up in 2019. Respiratory symptoms and health-related quality of life (HRQoL) were quantified. Lung function was measured by spirometry. FINDINGS: 1232 (83%) adults participated; spirometry was available for 1082 (73%). Mean (SD) age 49.5 (17.0) years, 278(23%) had ever smoked, and 724 (59%) were women. Forced expiratory volume in one second (FEV1) declined by 53.4 ml/year (95% CI: 49.0, 57.8) and forced vital capacity (FVC) by 45.2 ml/year (95% CI: 39.2, 50.5) . Chronic airflow obstruction increased from 9.5% (7.6, 11.6%) in 2014 to 17.5% (15.3, 19.9%) in 2019. There was no change in diagnosed asthma or in spirometry consistent with asthma or restriction. Rate of FEV1 decline was not associated with diagnosed Chronic obstructive pulmonary disease (COPD), asthma, or spirometry consistent with asthma, COPD, or restriction. HRQoL was adversely associated with respiratory symptoms (dyspnoea, wheeze, cough), previous tuberculosis, declining FEV1 and spirometry consistent with asthma or restriction. These differences exceeded the minimally important difference. INTERPRETATION: In this cohort, the increasing prevalence of COPD is associated with the high rate of FEV1 decline and lung function deficits present before recruitment. Respiratory symptoms and sub-optimal lung function are independently associated with reduced HRQoL.

Patient and health provider costs of integrated HIV, diabetes and hypertension ambulatory health services in low-income settings - an empirical socio-economic cohort study in Tanzania and Uganda.

BACKGROUND: Integration of health services might be an efficient strategy for managing multiple chronic conditions in sub-Saharan Africa, considering the scope of treatments and synergies in service delivery. Proven to promote compliance, integration may lead to increased economies-of-scale. However, evidence on the socio-economic consequences of integration for providers and patients is lacking. We assessed the clinical resource use, staff time, relative service efficiency and overall societal costs associated with integrating HIV, diabetes and hypertension services in single one-stop clinics where persons with one or more of these conditions were managed. METHODS: 2273 participants living with HIV infection, diabetes, or hypertension or combinations of these conditions were enrolled in 10 primary health facilities in Tanzania and Uganda and followed-up for up to 12 months. We collected data on resources used from all participants and on out-of-pocket costs in a sub-sample of 1531 participants, while a facility-level costing study was conducted at each facility. Health worker time per participant was assessed in a time-motion morbidity-stratified study among 228 participants. The mean health service cost per month and out-of-pocket costs per participant visit were calculated in 2020 US$ prices. Nested bootstrapping from these samples accounted for uncertainties. A data envelopment approach was used to benchmark the efficiency of the integrated services. Last, we estimated the budgetary consequences of integration, based on prevalence-based projections until 2025, for both country populations. RESULTS: Their average retention after 1 year service follow-up was 1911/2273 (84.1%). Five hundred and eighty-two of 2273 (25.6%) participants had two or all three chronic conditions and 1691/2273 (74.4%) had a single condition. During the study, 84/2239 (3.8%) participants acquired a second or third condition. The mean service costs per month of managing two conditions in a single participant were $39.11 (95% CI 33.99, 44.33), $32.18 (95% CI 30.35, 34.07) and $22.65 (95% CI 21.86, 23.43) for the combinations of HIV and diabetes and of HIV and hypertension, diabetes and hypertension, respectively. These costs were 34.4% (95% CI 17.9%, 41.9%) lower as compared to managing any two conditions separately in two different participants. The cost of managing an individual with all three conditions was 48.8% (95% CI 42.1%, 55.3%) lower as compared to managing these conditions separately. Out-of-pocket healthcare expenditure per participant per visit was $7.33 (95% CI 3.70, 15.86). This constituted 23.4% (95% CI 9.9, 54.3) of the total monthly service expenditure per patient and 11.7% (95% CI 7.3, 22.1) of their individual total household income. The integrated clinics' mean efficiency benchmark score was 0.86 (range 0.30-1.00) suggesting undercapacity that could serve more participants without compromising quality of care. The estimated budgetary consequences of managing multi-morbidity in these types of integrated clinics is likely to increase by 21.5% (range 19.2-23.4%) in the next 5 years, including substantial savings of 21.6% on the provision of integrated care for vulnerable patients with multi-morbidities. CONCLUSION: Integration of HIV services with diabetes and hypertension control reduces both health service and household costs, substantially. It is likely an efficient and equitable way to address the increasing burden of financially vulnerable households among Africa's ageing populations. Additional economic evidence is needed from longer-term larger-scale implementation studies to compare extended integrated care packages directly simultaneously with evidence on sustained clinical outcomes.

Management of non-urgent paediatric emergency department attendances by GPs: a retrospective observational study.

BACKGROUND: Non-urgent emergency department (ED) attendances are common among children. Primary care management may not only be more clinically appropriate, but may also improve patient experience and be more cost-effective. AIM: To determine the impact on admissions, waiting times, antibiotic prescribing, and treatment costs of integrating a GP into a paediatric ED. DESIGN AND SETTING: Retrospective cohort study explored non-urgent ED presentations in a paediatric ED in north-west England. METHOD: From 1 October 2015 to 30 September 2017, a GP was situated in the ED from 2.00 pm until 10.00 pm, 7 days a week. All children triaged as 'green' using the Manchester Triage System (non-urgent) were considered to be 'GP appropriate'. In cases of GP non-availability, children considered non-urgent were managed by ED staff. Clinical and operational outcomes, as well as the healthcare costs of children managed by GPs and ED staff across the same timeframe over a 2-year period were compared. RESULTS: Of 115 000 children attending the ED over the study period, a complete set of data were available for 13 099 categorised as 'GP appropriate'; of these, 8404 (64.2%) were managed by GPs and 4695 (35.8%) by ED staff. Median duration of ED stay was 39 min (interquartile range [IQR] 16-108 min) in the GP group and 165 min (IQR 104-222 min) in the ED group (P<0.001). Children in the GP group were less likely to be admitted as inpatients (odds ratio [OR] 0.16; 95% confidence interval [CI] = 0.13 to 0.20) and less likely to wait >4 hours before being admitted or discharged (OR 0.11; 95% CI = 0.08 to 0.13), but were more likely to receive antibiotics (OR 1.42; 95% CI = 1.27 to 1.58). Treatment costs were 18.4% lower in the group managed by the GP (P<0.0001). CONCLUSION: Given the rising demand for children's emergency services, GP in ED care models may improve the management of non-urgent ED presentations. However, further research that incorporates causative study designs is required.

Coverage outcomes (effects), costs, cost-effectiveness, and equity of two combinations of long-lasting insecticidal net (LLIN) distribution channels in Kenya: a two-arm study under operational conditions.

BACKGROUND: Malaria-endemic countries distribute long-lasting insecticidal nets (LLINs) through combined channels with ambitious, universal coverage (UC) targets. Kenya has used eight channels with variable results. To inform national decision-makers, this two-arm study compares coverage (effects), costs, cost-effectiveness, and equity of two combinations of LLIN distribution channels in Kenya. METHODS: Two combinations of five delivery channels were compared as 'intervention' and 'control' arms. The intervention arm comprised four channels: community health volunteer (CHV), antenatal and child health clinics (ANCC), social marketing (SM) and commercial outlets (CO). The control arm consisted of the intervention arm channels except mass campaign (MC) replaced CHV. Primary analysis used random sample household survey data, service-provider costs, and voucher or LLIN distribution data to compare between-arm effects, costs, cost-effectiveness, and equity. Secondary analyses compared costs and equity by channel. RESULTS: The multiple distribution channels used in both arms of the study achieved high LLIN ownership and use. The intervention arm had significantly lower reported LLIN use the night before the survey (84·8% [95% CI 83·0-86·4%] versus 89·2% [95% CI 87·8-90·5%], p < 0·0001), higher unit costs ($10·56 versus $7·17), was less cost-effective ($86·44, 95% range $75·77-$102·77 versus $69·20, 95% range $63·66-$77·23) and more inequitable (Concentration index [C.Ind] = 0·076 [95% CI 0·057 to 0·095 versus C.Ind = 0.049 [95% CI 0·030 to 0·067]) than the control arm. Unit cost per LLIN distributed was lowest for MC ($3·10) followed by CHV ($10·81) with both channels being moderately inequitable in favour of least-poor households. CONCLUSION: In line with best practices, the multiple distribution channel model achieved high LLIN ownership and use in this Kenyan study setting. The control-arm combination, which included MC, was the most cost-effective way to increase UC at household level. Mass campaigns, combined with continuous distribution channels, are an effective and cost-effective way to achieve UC in Kenya. The findings are relevant to other countries and donors seeking to optimise LLIN distribution. TRIAL REGISTRATION: The assignment of the intervention was not at the discretion of the investigators; therefore, this study did not require registration.

Determinants of Technical Efficiency in Public Hospitals: The Case of Saudi Arabia.

OBJECTIVE: In this study, we investigate the effect of the external environmental and institutional factors on the efficiency and the performance of the public hospitals affiliated to the Ministry of Health (MOH) in the Kingdom of Saudi Arabia (KSA). We estimate the demographic and socioeconomic characteristics of catchment populations that explain the demand for health services. METHODS: We apply descriptive analysis to explore what external factors (demographic and socioeconomic factors) can explain the observed differences in technical efficiency scores. We use Spearman's rank correlation, multivariate Tobit regression and Two-part model to measure the impact of the explanatory variables (i.e. population density, nationality, gender, age groups, economic status, health status, medical interventions and geographic location) on the efficiency scores. RESULTS: The analysis shows that the external factors had a significant influence on efficiency scores. We find significant associations between hospitals efficiency scores and number of populations in the catchment area, percentage of children (0-5 years old), the prevalence of infectious diseases, and the number of prescriptions dispensed from hospital's departments. Also, the scores significantly associate with the number of populations who faced financial hardships during medical treatments, and those received financial support from social administration. That indicates the hospitals that serve more patients in previous characteristics are relatively more technically efficient. CONCLUSIONS: The environmental and institutional factors have a crucial effect on efficiency and performance in public hospitals. In these regards, we suggested improvement of health policies and planning in respect to hospital efficiency and resource allocation, which consider the different demographic, socioeconomic and health status of the catchment populations (e.g., population density, poverty, health indicators and services utilization). The MOH should pay more attention to ensure appropriate allocation mechanisms of health resources and improve utilization of health services among the target populations, for securing efficient and equitable health services.

Do employer-sponsored health insurance schemes affect the utilisation of medically trained providers and out-of-pocket payments among ready-made garment workers? A case-control study in Bangladesh.

OBJECTIVE: We estimated the effect of an employer-sponsored health insurance (ESHI) scheme on healthcare utilisation of medically trained providers and reduction of out-of-pocket (OOP) expenditure among ready-made garment (RMG) workers. DESIGN: We used a case-control study design with cross-sectional preintervention and postintervention surveys. SETTINGS: The study was conducted among workers of seven purposively selected RMG factories in Shafipur, Gazipur in Bangladesh. PARTICIPANTS: In total, 1924 RMG workers (480 from the insured and 482 from the uninsured, in each period) were surveyed from insured and uninsured RMG factories, respectively, in the preintervention (October 2013) and postintervention (April 2015) period. INTERVENTIONS: We tested the effect of a pilot ESHI scheme which was implemented for 1 year. OUTCOME MEASURES: The outcome measures were utilisation of medically trained providers and reduction of OOP expenditure among RMG workers. We estimated difference-in-difference (DiD) and applied two-part regression model to measure the association between healthcare utilisation, OOP payments and ESHI scheme membership while controlling for the socioeconomic characteristics of workers. RESULTS: The ESHI scheme increased healthcare utilisation of medically trained providers by 26.1% (DiD=26.1; p<0.01) among insured workers compared with uninsured workers. While accounting for covariates, the effect on utilisation significantly reduced to 18.4% (p<0.05). The DiD estimate showed that OOP expenditure among insured workers decreased by -3700 Bangladeshi taka and -1100 Bangladeshi taka compared with uninsured workers when using healthcare services from medically trained providers or all provider respectively, although not significant. The multiple two-part models also reported similar results. CONCLUSION: The ESHI scheme significantly increased utilisation of medically trained providers among RMG workers. However, it has no significant effect on OOP expenditure. It can be recommended that an educational intervention be provided to RMG workers to improve their healthcare-seeking behaviours and increase their utilisation of ESHI-designated healthcare providers while keeping OOP payments low.

What matters when managing childhood fever in the emergency department? A discrete-choice experiment comparing the preferences of parents and healthcare professionals in the UK.

BACKGROUND: Fever among children is a leading cause of emergency department (ED) attendance and a diagnostic conundrum; yet robust quantitative evidence regarding the preferences of parents and healthcare providers (HCPs) for managing fever is scarce. OBJECTIVE: To determine parental and HCP preferences for the management of paediatric febrile illness in the ED. SETTING: Ten children's centres and a children's ED in England from June 2018 to January 2019. PARTICIPANTS: 98 parents of children aged 0-11 years, and 99 HCPs took part. METHODS: Nine focus-groups and coin-ranking exercises were conducted with parents, and a discrete-choice experiment (DCE) was conducted with both parents and HCPs, which asked respondents to choose their preferred option of several hypothetical management scenarios for paediatric febrile illness, with differing levels of visit time, out-of-pocket costs, antibiotic prescribing, HCP grade and pain/discomfort from investigations. RESULTS: The mean focus-group size was 4.4 participants (range 3-7), with a mean duration of 27.4 min (range 18-46 min). Response rates to the DCE among parents and HCPs were 94.2% and 98.2%, respectively. Avoiding pain from diagnostics, receiving a faster diagnosis and minimising wait times were major concerns for both parents and HCPs, with parents willing-to-pay £16.89 for every 1 hour reduction in waiting times. Both groups preferred treatment by consultants and nurse practitioners to treatment by doctors in postgraduate training. Parents were willing to trade-off considerable increases in waiting times (24.1 min) to be seen by consultants and to avoid additional pain from diagnostics (45.6 min). Reducing antibiotic prescribing was important to HCPs but not parents. CONCLUSIONS: Both parents and HCPs care strongly about reducing visit time, avoiding pain from invasive investigations and receiving diagnostic insights faster when managing paediatric febrile illness. As such, overdue advances in diagnostic capabilities should improve child and carer experience and HCP satisfaction considerably in managing paediatric febrile illness.

Addition of Flucytosine to Fluconazole for the Treatment of Cryptococcal Meningitis in Africa: A Multicountry Cost-effectiveness Analysis.

BACKGROUND: Mortality from cryptococcal meningitis remains very high in Africa. In the Advancing Cryptococcal Meningitis Treatment for Africa (ACTA) trial, 2 weeks of fluconazole (FLU) plus flucytosine (5FC) was as effective and less costly than 2 weeks of amphotericin-based regimens. However, many African settings treat with FLU monotherapy, and the cost-effectiveness of adding 5FC to FLU is uncertain. METHODS: The effectiveness and costs of FLU+5FC were taken from ACTA, which included a costing analysis at the Zambian site. The effectiveness of FLU was derived from cohorts of consecutively enrolled patients, managed in respects other than drug therapy, as were participants in ACTA. FLU costs were derived from costs of FLU+5FC in ACTA, by subtracting 5FC drug and monitoring costs. The cost-effectiveness of FLU+5FC vs FLU alone was measured as the incremental cost-effectiveness ratio (ICER). A probabilistic sensitivity analysis assessed uncertainties and a bivariate deterministic sensitivity analysis examined the impact of varying mortality and 5FC drug costs on the ICER. RESULTS: The mean costs per patient were US $847 (95% confidence interval [CI] $776-927) for FLU+5FC, and US $628 (95% CI $557-709) for FLU. The 10-week mortality rate was 35.1% (95% CI 28.9-41.7%) with FLU+5FC and 53.8% (95% CI 43.1-64.1%) with FLU. At the current 5FC price of US $1.30 per 500 mg tablet, the ICER of 5FC+FLU versus FLU alone was US $65 (95% CI $28-208) per life-year saved. Reducing the 5FC cost to between US $0.80 and US $0.40 per 500 mg resulted in an ICER between US $44 and US $28 per life-year saved. CONCLUSIONS: The addition of 5FC to FLU is cost-effective for cryptococcal meningitis treatment in Africa and, if made available widely, could substantially reduce mortality rates among human immunodeficiency virus-infected persons in Africa.

Cryptococcal Meningitis Screening and Community-based Early Adherence Support in People With Advanced Human Immunodeficiency Virus Infection Starting Antiretroviral Therapy in Tanzania and Zambia: A Cost-effectiveness Analysis.

BACKGROUND: A randomized trial demonstrated that among people living with late-stage human immunodeficiency virus (HIV) infection initiating antiretroviral therapy, screening serum for cryptococcal antigen (CrAg) combined with adherence support reduced all-cause mortality by 28%, compared with standard clinic-based care. Here, we present the cost-effectiveness. METHODS: HIV-infected adults with CD4 count <200 cells/µL were randomized to either CrAg screening plus 4 weekly home visits to provide adherence support or to standard clinic-based care in Dar es Salaam and Lusaka. The primary economic outcome was health service care cost per life-year saved as the incremental cost-effectiveness ratio (ICER), based on 2017 US dollars. We used nonparametric bootstrapping to assess uncertainties and univariate deterministic sensitivity analysis to examine the impact of individual parameters on the ICER. RESULTS: Among the intervention and standard arms, 1001 and 998 participants, respectively, were enrolled. The annual mean cost per participant in the intervention arm was US$339 (95% confidence interval [CI], $331-$347), resulting in an incremental cost of the intervention of US$77 (95% CI, $66-$88). The incremental cost was similar when analysis was restricted to persons with CD4 count <100 cells/µL. The ICER for the intervention vs standard care, per life-year saved, was US$70 (95% CI, $43-$211) for all participants with CD4 count up to 200 cells/µL and US$91 (95% CI, $49-$443) among those with CD4 counts <100 cells /µL. Cost-effectveness was most sensitive to mortality estimates. CONCLUSIONS: Screening for cryptococcal antigen combined with a short period of adherence support, is cost-effective in resource-limited settings.

The effect of a community-based health insurance on the out-of-pocket payments for utilizing medically trained providers in Bangladesh.

BACKGROUND: We aimed to estimate the effect of the community-based health insurance (CBHI) scheme on the magnitude of out-of-pocket (OOP) payments for the healthcare of the informal workers and their dependents. The CBHI scheme was piloted through a cooperative of informal workers, which covered seven unions in Chandpur Sadar Upazila, Bangladesh. METHODS: A quasi-experimental study was conducted using a case-comparison design. In total 1292 (646 insured and 646 uninsured) households were surveyed. Propensity score matching was done to minimize the observed baseline differences in the characteristics between the insured and uninsured groups. A two-part regression model was applied using both the probability of OOP spending and magnitude of such spending for healthcare in assessing the association with enrolment status in the CBHI scheme while controlling for other covariates. RESULTS: The OOP payment was 6.4% (p < 0.001) lower for medically trained provider (MTP) utilization among the insured compared with the uninsured. However, no significant difference was found in the OOP payments for healthcare utilization from all kind of providers, including the non-trained ones. CONCLUSIONS: The CBHI scheme could reduce OOP payments while providing better quality healthcare through the increased use of MTPs, which consequently could push the country towards universal health coverage.

Healthcare Costs and Life-years Gained From Treatments Within the Advancing Cryptococcal Meningitis Treatment for Africa (ACTA) Trial on Cryptococcal Meningitis: A Comparison of Antifungal Induction Strategies in Sub-Saharan Africa.

BACKGROUND: Mortality from cryptoccocal meningitis remains high. The ACTA trial demonstrated that, compared with 2 weeks of amphotericin B (AmB) plus flucystosine (5FC), 1 week of AmB and 5FC was associated with lower mortality and 2 weeks of oral flucanozole (FLU) plus 5FC was non-inferior. Here, we assess the cost-effectiveness of these different treatment courses. METHODS: Participants were randomized in a ratio of 2:1:1:1:1 to 2 weeks of oral 5FC and FLU, 1 week of AmB and FLU, 1 week of AmB and 5FC, 2 weeks of AmB and FLU, or 2 weeks of AmB and 5FC in Malawi, Zambia, Cameroon, and Tanzania. Data on individual resource use and health outcomes were collected. Cost-effectiveness was measured as incremental costs per life-year saved, and non-parametric bootstrapping was done. RESULTS: Total costs per patient were US $1442 for 2 weeks of oral FLU and 5FC, $1763 for 1 week of AmB and FLU, $1861 for 1 week of AmB and 5FC, $2125 for 2 weeks of AmB and FLU, and $2285 for 2 weeks of AmB and 5FC. Compared to 2 weeks of AmB and 5FC, 1 week of AmB and 5FC was less costly and more effective and 2 weeks of oral FLU and 5FC was less costly and as effective. The incremental cost-effectiveness ratio for 1 week of AmB and 5FC versus oral FLU and 5FC was US $208 (95% confidence interval $91-1210) per life-year saved. CLINICAL TRIALS REGISTRATION: ISRCTN45035509. CONCLUSIONS: Both 1 week of AmB and 5FC and 2 weeks of Oral FLU and 5FC are cost-effective treatments.

A Transparent Universal Health Coverage Index with Decomposition by Socioeconomic Groups: Application in Asian and African Settings.

BACKGROUND: Health and wellbeing as one of the Sustainable Development Goals requires all countries to achieve Universal Health Coverage (UHC). That is, all people must have access to healthcare when needed at an affordable price. While several indices were developed recently to assess UHC status, these indices appeared to be difficult for practitioners to apply without statistical knowledge. OBJECTIVE: This paper presents a transparent and step-by-step practical calculation method of such an index using Excel spreadsheets, applied to some Asian and African countries. We also decompose the contribution of socioeconomic groups to UHC index values. METHODS: We utilized the well known UHC illustration (three-dimensional box, showing population coverage, service coverage and financial protection) to calculate the UHC index. We also broke down the index into socioeconomic groups. For validation, correlation coefficients between our index and other UHC indices were calculated and the relationship of our index with out-of-pocket (OOP) payments was estimated. RESULTS: World Bank data from six Asian and 15 African countries on health-service coverage of people in five socioeconomic quintiles with financial protection were used to calculate our UHC index. Among the Asian countries, indices ranged between 26.0% (Nepal) and 58.7% (Kazakhstan), while in African countries indices ranged between 8.9% (Chad) and 55.3% (Namibia). Decomposition of the UHC index showed a higher contribution to the index by richer socioeconomic groups. The correlation coefficients between our estimated UHC index values and those of others ranged between 0.774 and 0.900. Our index reduced by 1.4% in response to a 1% increase in OOP payments. CONCLUSIONS: This spreadsheet approach for calculating the UHC index appeared to be useful, where the interrelation of UHC dimensions was easily observed. Decomposition of the index could be useful for policy-makers to identify the subpopulations and health services with need for further interventions towards UHC achievement.

The cost of diagnostic uncertainty: a prospective economic analysis of febrile children attending an NHS emergency department.

BACKGROUND: Paediatric fever is a common cause of emergency department (ED) attendance. A lack of prompt and definitive diagnostics makes it difficult to distinguish viral from potentially life-threatening bacterial causes, necessitating a cautious approach. This may result in extended periods of observation, additional radiography, and the precautionary use of antibiotics (ABs) prior to evidence of bacterial foci. This study examines resource use, service costs, and health outcomes. METHODS: We studied an all-year prospective, comprehensive, and representative cohort of 6518 febrile children (aged < 16 years), attending Alder Hey Children's Hospital, an NHS-affiliated paediatric care provider in the North West of England, over a 1-year period. Performing a time-driven and activity-based micro-costing, we estimated the economic impact of managing paediatric febrile illness, with focus on nurse/clinician time, investigations, radiography, and inpatient stay. Using bootstrapped generalised linear modelling (GLM, gamma, log), we identified the patient and healthcare provider characteristics associated with increased resource use, applying retrospective case-note identification to determine rates of potentially avoidable AB prescribing. RESULTS: Infants aged less than 3 months incurred significantly higher resource use than any other age group, at £1000.28 [95% CI £82.39-£2993.37] per child, (p < 0.001), while lesser experienced doctors exhibited 3.2-fold [95% CI 2.0-5.1-fold] higher resource use than consultants (p < 0.001). Approximately 32.4% of febrile children received antibiotics, and 7.1% were diagnosed with bacterial infections. Children with viral illnesses for whom antibiotic prescription was potentially avoidable incurred 9.9-fold [95% CI 6.5-13.2-fold] cost increases compared to those not receiving antibiotics, equal to an additional £1352.10 per child, predominantly resulting from a 53.9-h increase in observation and inpatient stay (57.1 vs. 3.2 h). Bootstrapped GLM suggested that infants aged below 3 months and those prompting a respiratory rate 'red flag', treatment by lesser experienced doctors, and Manchester Triage System (MTS) yellow or higher were statistically significant predictors of higher resource use in 100% of bootstrap simulations. CONCLUSION: The economic impact of diagnostic uncertainty when managing paediatric febrile illness is significant, and the precautionary use of antibiotics is strongly associated with increased costs. The use of ED resources is highest among infants (aged less than 3 months) and those infants managed by lesser experienced doctors, independent of clinical severity. Diagnostic advances which could increase confidence to withhold antibiotics may yield considerable efficiency gains in these groups, where the perceived risks of failing to identify potentially life-threatening bacterial infections are greatest.