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BACKGROUND: Chronic pain is a leading cause of disability. Radiofrequency denervation (RFD) is effective when performed according to guidelines for patients with correctly diagnosed zygapophyseal joint pain (ZJP). However, the cost-effectiveness of this method has not been fully explored. OBJECTIVE: The aim of this study was to analyze whether RFD is cost-effective for ZJP from a societal perspective. STUDY DESIGN: Cost effectiveness study based on an observational study. SETTING: An interventional pain management clinic in central Sweden. METHODS: Patients - This cost-effectiveness study was performed for all patients (n = 873) assessed between 2010 and 2016 at a specialized interventional pain clinic in Sweden. Those diagnosed with ZJP (n = 331, 37.9%) were treated with RFD and followed up for 1 year after the RFD. Using data collected from national registers, we determined the health care costs, medication costs, the patients' time and travel costs, and the patients' ability to work. The effects of RFD on quality-adjusted life years (QALY) and cost/QALY gained were calculated. RESULTS: On average, patients reported very low health-related quality of life (HRQoL; EQ-5D index: 0.212). After RFD, HRQoL increased significantly to 0.530 (P < 0.0001). Drug consumption and specialized health care consumption were reduced by 54% and 81%, respectively, and the cost/QALY gained from a societal perspective was 221,324 Swedish krona (USD ~26,008). The sensitivity analysis showed that the treatment was cost-effective in all scenarios evaluated, using the patients as their own controls. The cost/QALY gained from a health care perspective was 72,749 Swedish krona (USD ~8,548). LIMITATIONS: The results are based on data collected at one center. The results need to be compared with those from pain rehabilitation programs and should be confirmed using data from other centers. CONCLUSIONS: Patients referred for RFD in Sweden report extremely low HRQoL. HRQoL significantly increased following RFD in patients with ZJP. Medications and health care consumption decreased after RFD. RFD was cost-effective, and the sensitivity analysis yielded stable results in different scenarios. Therefore, RFD is a cost-effective treatment that meets the Swedish National Board of Health and Welfare criteria for a high priority treatment. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (NCT01835704) with Protocol ID SE-Dnr-2012-446-31M-1. https://clinicaltrials.gov/ct2/show/NCT01835704.

Background Harm reduction strategies commonly include needle and syringe programmes (NSP), opioid substitution therapy (OST) and interventions combining these two strategies. Despite the proven effectiveness of harm-reduction strategies in reducing human immunodeficiency virus (HIV) infection among injecting drug users (IDUs), no study has compared the cost-effectiveness of these interventions, nor the incremental cost effectiveness of combined therapy. Using data from the Global Fund, this study compares the cost-effectiveness of harm reduction strategies in Eastern Europe and Central Asia, using the Ukraine as a case study. Methods A Markov Monte Carlo simulation is carried out using parameters from the literature and cost data from the Global Fund. Effectiveness is presented as both QALYs and infections averted. Costs are measured in 2011 US dollars. Results The Markov Monte Carlo simulation estimates the cost-effectiveness ratio per infection averted as $487.4 [95% CI: 488.47-486.35] in NSP and $1145.9 [95% CI: 1143.39-1148.43] in OST. Combined intervention is more costly but more effective than the alternative strategies with a cost effectiveness ratio of $851.6[95% CI: 849.82-853.55]. The ICER of the combined strategy is $1086.9/QALY [95% CI: 1077.76:1096.24] compared with NSP, and $461.0/infection averted [95% CI: 452.98:469.04] compared with OST. These results are consistent with previous studies. Conclusions Despite the inherent limitations of retrospective data, this study provides evidence that harm-reduction interventions are a cost-effective way to reduce HIV prevalence. More research on into cost effectiveness in different settings, and the availability of fiscal space for government uptake of programmes, is required.

INTRODUCTION: Cutaneous leishmaniasis (CL), endemic in Bolivia, mostly affects poor people in rainforest areas. The current first-line treatment consists of systemic pentavalent antimonials (SPA) for 20 days and is paid for by the Ministry of Health (MoH). Long periods of drug shortages and a lack of safe conditions to deliver treatment are challenges to implementation. Intralesional pentavalent antimonials (ILPA) are an alternative to SPA. This study aims to compare the cost of ILPA and SPA, and to estimate the health and economic impacts of changing the first-line treatment for CL in a Bolivian endemic area. METHODS: The cost-per-patient treated was estimated for SPA and ILPA from the perspectives of the MoH and society. The quantity and unit costs of medications, staff time, transportation and loss of production were obtained through a health facility survey (N = 12), official documents and key informants. A one-way sensitivity analysis was conducted on key parameters to evaluate the robustness of the results. The annual number of patients treated and the budget impact of switching to ILPA as the first-line treatment were estimated under different scenarios of increasing treatment utilization. Costs were reported in 2017 international dollars (1 INT$ = 3.10 BOB). RESULTS: Treating CL using ILPA was associated with a cost-saving of $248 per-patient-treated from the MoH perspective, and $688 per-patient-treated from the societal perspective. Switching first-line treatment to ILPA while maintaining the current budget would allow two-and-a-half times the current number of patients to be treated. ILPA remained cost-saving compared to SPA in the sensitivity analysis. CONCLUSIONS: The results of this study support a shift to ILPA as the first-line treatment for CL in Bolivia and possibly in other South American countries.

Background: Limited research is available about the impact of healthcare reforms on healthcare utilization accord‑ing to socioeconomic group. Although most health reforms in Latin America have focused on reducing the gapbetween the most advantaged and disadvantaged groups and improving the quality of health services, the available information has shown limited progress. Therefore, this study assessed whether the recent Ecuadorian healthcare reform (2007–2017) contributed to decreasing the socioeconomic inequalities in healthcare utilization. Methods: We used data from the National Living Standards Measurement surveys conducted in 2006 and 2014. Unmet healthcare needs (UHCN) were used as the dependent variable and proxy for difculties in accessing health services. Place of residence, ethnicity, education and wealth were selected as indicators of socioeconomic status. The slope and relative inequality indexes were calculated for adult men and women for each period and socioeconomic variable. A multiplicative interaction term between midpoint scores and time was applied to estimate changes ininequalities over time. Sample weights were applied to all analyses, and 95% confdence intervals were calculated to assess statistical signifcance in the regression analysis. Results: In 2006, the poor, Indigenous, those living in rural areas and with low education had lower access to health services. In 2014, the overall prevalence of UHCN decreased from 27 to 18% and was higher in women than men. Statistically signifcant reductions of refraining were observed in absolute and relative terms in all social groups, both in men and women. Conclusions: Our results showed remarkable and signifcant decreases in inequalities in all examined socioeconomic groups in absolute and relative terms in this period. Although a new model of healthcare was established to achieve universal health coverage, its performance must be continuously evaluated and monitored with specifc indicators. Further studies are also needed to identify the main barriers that contribute to UHCN among socially disadvantaged groups.

BACKGROUND: Over the last 12 years, Ecuador has implemented comprehensive health sector reform to ensure equitable access to health care services according to need. While there have been important achievements in terms of health care coverage, the effects of these reforms on socioeconomic inequalities in health care have not been analysed. The present study assesses whether the health care reforms implemented in the decade between 2007 and 2017 have contributed to reducing the socioeconomic inequalities in women's health care access. METHODS: The present study was based on two waves (2006 and 2014) of the Living Standards Measurement Survey conducted in Ecuador. Data from women of reproductive age (15 to 49 years) were analysed to evaluate health care coverage across three indicators: skilled birth attendance, cervical cancer screening, and the use of modern contraceptives. Absolute risk differences were calculated between the heath care indicators and the socioeconomic variables using binomial regression analysis for each time period. The Slope Index of Inequality (SII) was also calculated for each socioeconomic variable and period. A multiplicative interaction term between the socioeconomic variables and period was included to assess the changes in socioeconomic inequalities in health care over time. RESULTS: Access to health care increased in the three studied outcomes during the health sector reform. Significant reductions in inequality in skilled birth attendance were observed in all socioeconomic variables except in the occupational class. Cervical cancer screening inequalities increased according to education and occupation, but decreased by wealth. Only a poorer education was observed for modern contraceptive use. CONCLUSIONS: While most socioeconomic inequalities in skilled birth attendance decreased during the reform period, this was not the case for inequalities in cervical cancer screening or the use of modern contraceptives. Further studies are needed to address the social determinants of these health inequalities.

Background: Rwanda has made tremendous progress in reduction of maternal mortality in the last twenty years. Antenatal care is believed to have played a role in that progress. In late 2016, the World Health Organization published new antenatal care guidelines recommending an increase from four visits during pregnancy to eight contacts with skilled personnel, among other changes. There is ongoing debate regarding the cost implications and potential outcomes countries can expect, if they make that shift. For Rwanda, a necessary starting point is to understand the cost of current antenatal care practice, which, according to our knowledge, has not been documented so far. Methods: Cost information was collected from Kigali City and Northern province of Rwanda through two cross-sectional surveys: a household-based survey among women who had delivered a year before the interview (N = 922) and a health facility survey in three public, two faith-based, and one private health facility. A micro costing approach was used to collect health facility data. Household costs included time and transport. Results are reported in 2015 USD. Results: The societal cost (household + health facility) of antenatal care for the four visits according to current Rwandan guidelines was estimated at $160 in the private health facility and $44 in public and faith-based health facilities. The first visit had the highest cost ($75 in private and $21 in public and faith-based health facilities) compared to the three other visits. Drugs and consumables were the main input category accounting for 54% of the total cost in the private health facility and for 73% in the public and faith-based health facilities. Conclusions: The unit cost of providing antenatal care services is considerably lower in public than in private health facilities. The household cost represents a small proportion of the total, ranging between 3% and 7%; however, it is meaningful for low-income families. There is a need to do profound equity analysis regarding the accessibility and use of antenatal care services, and to consider ways to reduce households' time cost as a possible barrier to the use of antenatal care.

OBJECTIVES: High-quality evidence of effectiveness and cost-effectiveness is rarely available and relevant for health policy decisions in low-resource settings. In such situations, innovative approaches are needed to generate locally relevant evidence. This study aims to inform decision-making on antenatal care (ANC) recommendations in Rwanda by estimating the incremental cost-effectiveness of the recent (2016) WHO antenatal care recommendations compared to current practice in Rwanda. METHODS: Two health outcome scenarios (optimistic, pessimistic) in terms of expected maternal and perinatal mortality reduction were constructed using expert elicitation with gynaecologists/obstetricians currently practicing in Rwanda. Three costing scenarios were constructed from the societal perspective over a 1-year period. The two main inputs to the cost analyses were a Monte Carlo simulation of the distribution of ANC attendance for a hypothetical cohort of 373,679 women and unit cost estimation of the new recommendations using data from a recent primary costing study of current ANC practice in Rwanda. Results were reported in 2015 USD and compared with the 2015 Rwandan per-capita gross domestic product (US$ 697). RESULTS: Incremental health gains were estimated as 162,509 life-years saved (LYS) in the optimistic scenario and 65,366 LYS in the pessimistic scenario. Incremental cost ranged between $5.8 and $11 million (an increase of 42% and 79%, respectively, compared to current practice) across the costing scenarios. In the optimistic outcome scenario, incremental cost per LYS ranged between $36 (for low ANC attendance) and $67 (high ANC attendance), while in the pessimistic outcome scenario, it ranged between $90 (low ANC attendance) and $168 (high ANC attendance) per LYS. Incremental cost effectiveness was below the GDP-based thresholds in all six scenarios. DISCUSSION: Implementing the new WHO ANC recommendations in Rwanda would likely be very cost-effective; however, the additional resource requirements are substantial. This study demonstrates how expert elicitation combined with other data can provide an affordable source of locally relevant evidence for health policy decisions in low-resource settings. ; Originally included in thesis in manuscript form

WHO recommends participatory learning and action cycles with women's groups as a cost-effective strategy to reduce neonatal deaths. Coverage is a determinant of intervention effectiveness, but little is known about why cost-effectiveness estimates vary significantly. This article reanalyses primary cost data from six trials in India, Nepal, Bangladesh and Malawi to describe resource use, explore reasons for differences in costs and cost-effectiveness ratios, and model the cost of scale-up. Primary cost data were collated, and costing methods harmonized. Effectiveness was extracted from a meta-analysis and converted to neonatal life-years saved. Cost-effectiveness ratios were calculated from the provider perspective compared with current practice. Associations between unit costs and cost-effectiveness ratios with coverage, scale and intensity were explored. Scale-up costs and outcomes were modelled using local unit costs and the meta-analysis effect estimate for neonatal mortality. Results were expressed in 2016 international dollars. The average cost was $203 (range: $61-$537) per live birth. Start-up costs were large, and spending on staff was the main cost component. The cost per neonatal life-year saved ranged from $135 to $1627. The intervention was highly cost-effective when using income-based thresholds. Variation in cost-effectiveness across trials was strongly correlated with costs. Removing discounting of costs and life-years substantially reduced all cost-effectiveness ratios. The cost of rolling out the intervention to rural populations ranges from 1.2% to 6.3% of government health expenditure in the four countries. Our analyses demonstrate the challenges faced by economic evaluations of community-based interventions evaluated using a cluster randomized controlled trial design. Our results confirm that women's groups are a cost-effective and potentially affordable strategy for improving birth outcomes among rural populations.

BACKGROUND: Undernutrition during pregnancy leads to low birthweight, poor growth and inter-generational undernutrition. We did a non-blinded cluster-randomised controlled trial in the plains districts of Dhanusha and Mahottari, Nepal to assess the impact on birthweight and weight-for-age z-scores among children aged 0-16 months of community-based participatory learning and action (PLA) women's groups, with and without food or cash transfers to pregnant women. METHODS: We randomly allocated 20 clusters per arm to four arms (average population/cluster = 6150). All consenting married women aged 10-49 years, who had not had tubal ligation and whose husbands had not had vasectomy, were monitored for missed menses. Between 29 Dec 2013 and 28 Feb 2015 we recruited 25,092 pregnant women to surveillance and interventions: PLA alone (n = 5626); PLA plus food (10 kg/month of fortified wheat-soya 'Super Cereal', n = 6884); PLA plus cash (NPR750≈US$7.5/month, n = 7272); control (existing government programmes, n = 5310). 539 PLA groups discussed and implemented strategies to improve low birthweight, nutrition in pregnancy and hand washing. Primary outcomes were birthweight within 72 hours of delivery and weight-for-age z-scores at endline (age 0-16 months). Only children born to permanent residents between 4 June 2014 and 20 June 2015 were eligible for intention to treat analyses (n = 10936), while in-migrating women and children born before interventions had been running for 16 weeks were excluded. Trial status: completed. RESULTS: In PLA plus food/cash arms, 94-97% of pregnant women attended groups and received a mean of four transfers over their pregnancies. In the PLA only arm, 49% of pregnant women attended groups. Due to unrest, the response rate for birthweight was low at 22% (n = 2087), but response rate for endline nutritional and dietary measures exceeded 83% (n = 9242). Compared to the control arm (n = 464), mean birthweight was significantly higher in the PLA plus food arm by 78·0 g (95% CI 13·9, 142·0; n = 626) and not significantly higher in PLA only and PLA plus cash arms by 28·9 g (95% CI -37·7, 95·4; n = 488) and 50·5 g (95% CI -15·0, 116·1; n = 509) respectively. Mean weight-for-age z-scores of children aged 0-16 months (average age 9 months) sampled cross-sectionally at endpoint, were not significantly different from those in the control arm (n = 2091). Differences in weight for-age z-score were as follows: PLA only -0·026 (95% CI -0·117, 0·065; n = 2095); PLA plus cash -0·045 (95% CI -0·133, 0·044; n = 2545); PLA plus food -0·033 (95% CI -0·121, 0·056; n = 2507). Amongst many secondary outcomes tested, compared with control, more institutional deliveries (OR: 1.46 95% CI 1.03, 2.06; n = 2651) and less colostrum discarding (OR:0.71 95% CI 0.54, 0.93; n = 2548) were found in the PLA plus food arm but not in PLA alone or in PLA plus cash arms. INTERPRETATION: Food supplements in pregnancy with PLA women's groups increased birthweight more than PLA plus cash or PLA alone but differences were not sustained. Nutrition interventions throughout the thousand-day period are recommended. TRIAL REGISTRATION: ISRCTN75964374.

Background: Undernutrition during pregnancy leads to low birthweight, poor growth and inter-generational undernutrition. We did a non-blinded cluster-randomised controlled trial in the plains districts of Dhanusha and Mahottari, Nepal to assess the impact on birthweight and weight-for-age z-scores among children aged 0–16 months of community-based participatory learning and action (PLA) women's groups, with and without food or cash transfers to pregnant women. Methods: We randomly allocated 20 clusters per arm to four arms (average population/cluster = 6150). All consenting married women aged 10–49 years, who had not had tubal ligation and whose husbands had not had vasectomy, were monitored for missed menses. Between 29 Dec 2013 and 28 Feb 2015 we recruited 25,092 pregnant women to surveillance and interventions: PLA alone (n = 5626); PLA plus food (10 kg/month of fortified wheat-soya 'Super Cereal', n = 6884); PLA plus cash (NPR750≈US$7.5/month, n = 7272); control (existing government programmes, n = 5310). 539 PLA groups discussed and implemented strategies to improve low birthweight, nutrition in pregnancy and hand washing. Primary outcomes were birthweight within 72 hours of delivery and weight-for-age z-scores at endline (age 0–16 months). Only children born to permanent residents between 4 June 2014 and 20 June 2015 were eligible for intention to treat analyses (n = 10936), while in-migrating women and children born before interventions had been running for 16 weeks were excluded. Trial status: completed. Results: In PLA plus food/cash arms, 94–97% of pregnant women attended groups and received a mean of four transfers over their pregnancies. In the PLA only arm, 49% of pregnant women attended groups. Due to unrest, the response rate for birthweight was low at 22% (n = 2087), but response rate for endline nutritional and dietary measures exceeded 83% (n = 9242). Compared to the control arm (n = 464), mean birthweight was significantly higher in the PLA plus food arm by 78·0 g (95% CI 13·9, 142·0; n = 626) and not significantly higher in PLA only and PLA plus cash arms by 28·9 g (95% CI -37·7, 95·4; n = 488) and 50·5 g (95% CI -15·0, 116·1; n = 509) respectively. Mean weight-for-age z-scores of children aged 0–16 months (average age 9 months) sampled cross-sectionally at endpoint, were not significantly different from those in the control arm (n = 2091). Differences in weight for-age z-score were as follows: PLA only -0·026 (95% CI -0·117, 0·065; n = 2095); PLA plus cash -0·045 (95% CI -0·133, 0·044; n = 2545); PLA plus food -0·033 (95% CI -0·121, 0·056; n = 2507). Amongst many secondary outcomes tested, compared with control, more institutional deliveries (OR: 1.46 95% CI 1.03, 2.06; n = 2651) and less colostrum discarding (OR:0.71 95% CI 0.54, 0.93; n = 2548) were found in the PLA plus food arm but not in PLA alone or in PLA plus cash arms. Interpretation: Food supplements in pregnancy with PLA women's groups increased birthweight more than PLA plus cash or PLA alone but differences were not sustained. Nutrition interventions throughout the thousand-day period are recommended.

Background Undernutrition during pregnancy leads to low birthweight, poor growth and inter-generational undernutrition. We did a non-blinded cluster-randomised controlled trial in the plains districts of Dhanusha and Mahottari, Nepal to assess the impact on birthweight and weight-for-age z-scores among children aged 0–16 months of community-based participatory learning and action (PLA) women's groups, with and without food or cash transfers to pregnant women. Methods We randomly allocated 20 clusters per arm to four arms (average population/cluster = 6150). All consenting married women aged 10–49 years, who had not had tubal ligation and whose husbands had not had vasectomy, were monitored for missed menses. Between 29 Dec 2013 and 28 Feb 2015 we recruited 25,092 pregnant women to surveillance and interventions: PLA alone (n = 5626); PLA plus food (10 kg/month of fortified wheat-soya 'Super Cereal', n = 6884); PLA plus cash (NPR750≈US$7.5/month, n = 7272); control (existing government programmes, n = 5310). 539 PLA groups discussed and implemented strategies to improve low birthweight, nutrition in pregnancy and hand washing. Primary outcomes were birthweight within 72 hours of delivery and weight-for-age z-scores at endline (age 0–16 months). Only children born to permanent residents between 4 June 2014 and 20 June 2015 were eligible for intention to treat analyses (n = 10936), while in-migrating women and children born before interventions had been running for 16 weeks were excluded. Trial status: completed. Results In PLA plus food/cash arms, 94–97% of pregnant women attended groups and received a mean of four transfers over their pregnancies. In the PLA only arm, 49% of pregnant women attended groups. Due to unrest, the response rate for birthweight was low at 22% (n = 2087), but response rate for endline nutritional and dietary measures exceeded 83% (n = 9242). Compared to the control arm (n = 464), mean birthweight was significantly higher in the PLA plus food arm by 78·0 g (95% CI 13·9, 142·0; n = 626) and not significantly higher in PLA only and PLA plus cash arms by 28·9 g (95% CI -37·7, 95·4; n = 488) and 50·5 g (95% CI -15·0, 116·1; n = 509) respectively. Mean weight-for-age z-scores of children aged 0–16 months (average age 9 months) sampled cross-sectionally at endpoint, were not significantly different from those in the control arm (n = 2091). Differences in weight for-age z-score were as follows: PLA only -0·026 (95% CI -0·117, 0·065; n = 2095); PLA plus cash -0·045 (95% CI -0·133, 0·044; n = 2545); PLA plus food -0·033 (95% CI -0·121, 0·056; n = 2507). Amongst many secondary outcomes tested, compared with control, more institutional deliveries (OR: 1.46 95% CI 1.03, 2.06; n = 2651) and less colostrum discarding (OR:0.71 95% CI 0.54, 0.93; n = 2548) were found in the PLA plus food arm but not in PLA alone or in PLA plus cash arms. Interpretation Food supplements in pregnancy with PLA women's groups increased birthweight more than PLA plus cash or PLA alone but differences were not sustained. Nutrition interventions throughout the thousand-day period are recommended. Trial registration ISRCTN75964374.