Ending malnutrition in all its forms requires scaling up proven nutrition interventions and much more: a 129-country analysis

Abstract Background Sustainable Development Goal (SDG) 2.2 calls for an end to all forms of malnutrition, with 2025 targets of a 40% reduction in stunting (relative to 2012), for wasting to occur in less than 5% of children, and for a 50% reduction in anaemia in women (15–49 years). We assessed the likelihood of countries reaching these targets by scaling up proven interventions and identified priority interventions, based on cost-effectiveness. Methods For 129 countries, the Optima Nutrition model was used to compare 2019–2030 nutrition outcomes between a status quo (maintained intervention coverage) scenario and a scenario where outcome-specific interventions were scaled up to 95% coverage over 5 years. The average cost-effectiveness of each intervention was calculated as it was added to an expanding package of interventions. Results Of the 129 countries modelled, 46 (36%), 66 (51%) and 0 (0%) were on track to achieve the stunting, wasting and anaemia targets respectively. Scaling up 18 nutrition interventions increased the number of countries reaching the SDG 2.2 targets to 50 (39%), 83 (64%) and 7 (5%) respectively. Intermittent preventative treatment of malaria during pregnancy (IPTp), infant and young child feeding education, vitamin A supplementation and lipid-based nutrition supplements for children produced 88% of the total impact on stunting, with average costs per case averted of US$103, US$267, US$556 and US$1795 when interventions were consecutively scaled up, respectively. Vitamin A supplementation and cash transfers produced 100% of the total global impact on prevention of wasting, with average costs per case averted of US$1989 and US$19,427, respectively. IPTp, iron and folic acid supplementation for non-pregnant women, and multiple micronutrient supplementation for pregnant women produced 85% of the total impact on anaemia prevalence, with average costs per case averted of US$9, US$35 and US$47, respectively. Conclusions Prioritising nutrition investment to the most cost-effective interventions within the country context can maximise the impact of funding. A greater focus on complementing nutrition-specific interventions with nutrition-sensitive ones that address the social determinants of health is critical to reach the SDG targets.

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Impact of vitamin A supplementation in anaemia during pregnancy: a randomized double blind controlled clinical trial

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20182332 ◽

2018 ◽

Vol 7 (6) ◽

pp. 2262

Author(s):

Shakun Singh ◽

Rachna Chaudhary ◽

Vandana Dhama ◽

Anu Singh ◽

Urmila Karya

Keyword(s):

Clinical Trial ◽

Vitamin A ◽

Pregnant Women ◽

Controlled Clinical Trial ◽

Double Blind ◽

Vitamin A Supplementation ◽

Elemental Iron ◽

Group A ◽

Group B ◽

The Impact

Background: To study the impact of Vitamin A supplementation in anaemia during Pregnancy and thus improving maternal and fetal outcome a Randomized double blind controlled clinical trial was conducted in Department of Obstetrics and Gynaecology, L.L.R.M. Medical college Meerut involving 250 pregnant women in late pregnancy 18-28 weeks with haemoglobin levels <11 g% (7-11 g%)..Methods: The study subjects were divided into two groups: Group A (n=125): Received daily supplement containing Iron (60 mg elemental iron) + Folate (500 mcg) + Vitamin A 20,000 IU weekly for a minimum of 12 weeks. Group B (n=125): Received daily supplement containing iron (60 mg elemental iron) + Folate (500 mcg) for a minimum of 12 weeks.Results: Maximum patients were uneducated belonging to low socioeconomic status. The mean haemoglobin values in Group A and Group B increased from 9.674±1.05 and 9.53±1.04 to 12.2±0.89 and 10.82±1.06 respectively after supplementation. Similarily Serum Ferritin levels increased from 15.96±2.94 and 15.70±2.83 to 78.40±17.82 and 58.64±11.93. Mean corpuscular volume, packed cell volume and red blood cell counts also increased significantly. Maximum haemoglobin levels were achieved with both vitamin A and iron supplementation. The proportion of women who became non anaemic was 97.17% in Group A vs 68.69% in Group B.Conclusions: Vitamin A supplementation improves anaemia and also dramatically improves iron stores in anaemic pregnant women.

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Cost-effectiveness and feasibility of conditional economic incentives and motivational interviewing to improve HIV health outcomes of adolescents living with HIV in Anambra State, Nigeria

BMC Health Services Research ◽

10.1186/s12913-021-06718-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Obinna Ikechukwu Ekwunife ◽

Chinelo Janefrances Ofomata ◽

Charles Ebuka Okafor ◽

Maureen Ugonwa Anetoh ◽

Stephen Okorafor Kalu ◽

...

Keyword(s):

Viral Load ◽

Cost Effectiveness ◽

Service Delivery ◽

Motivational Interviewing ◽

Cost Effective ◽

Economic Incentives ◽

Additional Patient ◽

Incentive Scheme ◽

The Cost ◽

The Impact

Abstract Background In sub-Saharan Africa, there is increasing mortality and morbidity of adolescents due to poor linkage, retention in HIV care and adherence to antiretroviral therapy (ART). This is a result of limited adolescent-centred service delivery interventions. This cost-effectiveness and feasibility study were piggybacked on a cluster-randomized trial that assessed the impact of an adolescent-centred service delivery intervention. The service delivery intervention examined the impact of an incentive scheme consisting of conditional economic incentives and motivational interviewing on the health outcomes of adolescents living with HIV in Nigeria. Method A cost-effectiveness analysis from the healthcare provider’s perspective was performed to assess the cost per additional patient achieving undetected viral load through the proposed intervention. The cost-effectiveness of the incentive scheme over routine care was estimated using the incremental cost-effectiveness ratio (ICER), expressed as cost/patient who achieved an undetectable viral load. We performed a univariate sensitivity analysis to examine the effect of key parameters on the ICER. An in-depth interview was conducted on the healthcare personnel in the intervention arm to explore the feasibility of implementing the service delivery intervention in HIV treatment hospitals in Nigeria. Result The ICER of the Incentive Scheme intervention compared to routine care was US$1419 per additional patient with undetectable viral load. Going by the cost-effectiveness threshold of US$1137 per quality-adjusted life-years suggested by Woods et al., 2016, the intervention was not cost-effective. The sensitivity test showed that the intervention will be cost-effective if the frequency of CD4 count and viral load tests are reduced from quarterly to triannually. Healthcare professionals reported that patients’ acceptance of the intervention was very high. Conclusion The conditional economic incentives and motivational interviewing was not cost-effective, but can become cost-effective if the frequency of HIV quality of life indicator tests are performed 1–3 times per annum. Patients’ acceptance of the intervention was very high. However, healthcare professionals believed that sustaining the intervention may be difficult unless factors such as government commitment and healthcare provider diligence are duly addressed. Trial registration This trial is registered in the WHO International Clinical Trials Registry through the WHO International Registry Network (PACTR201806003040425).

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

Clinical Infectious Diseases ◽

10.1093/cid/ciz163 ◽

2019 ◽

Vol 70 (1) ◽

pp. 26-29 ◽

Cited By ~ 3

Author(s):

Tinevimbo Shiri ◽

Angela Loyse ◽

Lawrence Mwenge ◽

Tao Chen ◽

Shabir Lakhi ◽

...

Keyword(s):

Sensitivity Analysis ◽

Cost Effectiveness ◽

Cryptococcal Meningitis ◽

Cost Effective ◽

Immunodeficiency Virus ◽

The Mean ◽

The Cost ◽

The Impact ◽

Costing Analysis ◽

Very High

Abstract 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.

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The impact of different doses of vitamin A supplementation on male and female mortality. A randomised trial from Guinea-Bissau

BMC Pediatrics ◽

10.1186/1471-2431-11-77 ◽

2011 ◽

Vol 11 (1) ◽

Cited By ~ 8

Author(s):

Dorthe Yakymenko ◽

Christine S Benn ◽

Cesario Martins ◽

Birgitte R Diness ◽

Ane B Fisker ◽

...

Keyword(s):

Vitamin A ◽

Randomised Trial ◽

Female Mortality ◽

Vitamin A Supplementation ◽

Male And Female ◽

Guinea Bissau ◽

The Impact ◽

Different Doses

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Early neonatal vitamin A supplementation and infant mortality: an individual participant data meta-analysis of randomised controlled trials

Archives of Disease in Childhood ◽

10.1136/archdischild-2018-315242 ◽

2018 ◽

Vol 104 (3) ◽

pp. 217-226 ◽

Cited By ~ 8

Author(s):

Keyword(s):

Infant Mortality ◽

Vitamin A ◽

Maternal Education ◽

Vitamin A Deficiency ◽

Population Characteristics ◽

Infant Survival ◽

Vitamin A Supplementation ◽

Maternal Vitamin ◽

Early Infant ◽

The Impact

BackgroundBiannual vitamin A supplementation is a well-established survival tool for preschool children 6 months and older in vitamin A deficient populations but this schedule misses the opportunity to intervene on most young infant deaths. Randomised trials of neonatal vitamin A supplementation (NVAS) in the first few days of life to assess its impact on under 6-month mortality in low/middle-income countries have had varying results.MethodsInvestigators of 11 published randomised placebo-controlled NVAS trials (n=163 567 children) reanalysed their data according to an agreed plan and pooled the primary outcomes of mortality from supplementation through 6 and 12 months of age using random effects models and meta-regression. One investigator withdrew but allowed use of the data.FindingsOverall there was no effect of NVAS on infant survival through 6 (risk ratio (RR) 0.97; 95% CI 0.89 to 1.06) or 12 months of age (RR 1.00; 95% CI 0.93 to 1.08) but results varied by study population characteristics.NVAS significantly reduced 6-month mortality among the trials conducted in Southern Asia (RR 0.87; 95% CI 0.77 to 0.98), in contexts with moderate or severe vitamin A deficiency (defined as 10% or higher proportion of women with serum retinol <0.7 µmol/L or 5% or more women with night blindness) (RR 0.87; 95% CI 0.80 to 0.94), early infant mortality was 30 or more per 1000 live births (RR 0.91; 95% CI 0.85 to 0.98), 75% or more of infant mortality occurred in the first 6 months of life (RR 0.92; 95% CI 0.84 to 1.01), or where >32% mothers had no schooling (RR 0.88; 95% CI 0.80 to 0.96). NVAS did not reduce mortality in the first 6 months of life in trials conducted in Africa, in contexts characterised by a low prevalence of vitamin A deficiency, lower rates of infant mortality and where maternal education was more prevalent. There was a suggestion of increased infant mortality in trials conducted in Africa (RR 1.07; 95% CI 1.00 to 1.15).Individual-level characteristics such as sex, birth weight, gestational age and size, age at dosing, parity, time of breast feeding initiation, maternal education and maternal vitamin A supplementation did not modify the impact of NVAS.ConclusionNVAS reduced infant mortality in South Asia, in contexts where the prevalence of maternal vitamin A deficiency is moderate to severe and early infant mortality is high; but it had no beneficial effect on infant survival in Africa, in contexts where the prevalence of maternal vitamin A deficiency is lower, early infant mortality is low.

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Projecting the impact of nutrition policy to improve child stunting: A case study in Guatemala using the Lives Saved Tool

10.1101/2021.05.24.21256641 ◽

2021 ◽

Author(s):

Scott Tschida ◽

Ana Cordon ◽

Gabriela Asturias ◽

Mónica Mazariegos ◽

María F Kroker-Lobos ◽

...

Keyword(s):

Scaling Up ◽

Nutrition Policy ◽

Nutrition Interventions ◽

Historical Trends ◽

Intervention Coverage ◽

Child Stunting ◽

Lives Saved Tool ◽

Global Health Issue ◽

The Impact

Background: Child stunting is a critical global health issue. Guatemala has one of the world′s highest levels of stunting despite sustained commitment to international nutrition policy best-practices endorsed by the Scaling Up Nutrition movement (SUN). Our objective was to use Guatemala as a case study by projecting the impact of a recently published national nutrition policy, the Great Crusade, that is consistent with SUN principles. Methods: We used the Lives Saved Tool (LiST) to project the scaling-up of nutrition interventions proposed in the Great Crusade and recommended by SUN. Our outcomes were changes in stunting prevalence, number of stunting cases averted, and number of cases averted by intervention in children under five years of age from 2020–2030. We considered four scenarios: (1) intervention coverage continues based on historical trends, (2) coverage targets in the Great Crusade are achieved, (3) coverage targets in the Great Crusade are achieved with reduced fertility risk, and (4) coverage reaches an aspirational level. Results: All scenarios led to modest reductions in stunting prevalence. In 2024, stunting prevalence was estimated to change by -0.1‰ (95‰ CI 0.0‰ to -0.2‰) if historical trends continue, -1.1‰ (95‰ CI -0.8‰ to -1.5‰) in the Great Crusade scenario, and -2.2‰ (95‰ CI -1.6‰ to -3.0‰) in the aspirational scenario. In 2030, we projected a stunting prevalence of -0.4‰ (95‰ CI -0.2‰ to -0.8‰) and -3.7‰ (95‰ CI -2.8‰ to -5.1‰) in the historical trends and aspirational scenario, respectively. Complementary feeding, sanitation, and breastfeeding were the most impactful interventions across models. Conclusions: Targeted reductions in child stunting prevalence in Guatemala are unlikely to be achieved solely based on increases in intervention coverage. Our results show the limitations of current paradigms recommended by the international nutrition community. Policies and strategies are needed that address the broader structural drivers of stunting.

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A Cost-Effectiveness Analysis of Newborn Screening for Severe Combined Immunodeficiency in the UK

International Journal of Neonatal Screening ◽

10.3390/ijns5030028 ◽

2019 ◽

Vol 5 (3) ◽

pp. 28 ◽

Cited By ~ 2

Author(s):

Alice Bessey ◽

James Chilcott ◽

Joanna Leaviss ◽

Carmen de la Cruz ◽

Ruth Wong

Keyword(s):

Cost Effectiveness ◽

Severe Combined Immunodeficiency ◽

Cost Effective ◽

Sensitivity Analyses ◽

Combined Immunodeficiency ◽

Tree Model ◽

Life Years ◽

The Uk ◽

The Cost ◽

The Impact

Severe combined immunodeficiency (SCID) can be detected through newborn bloodspot screening. In the UK, the National Screening Committee (NSC) requires screening programmes to be cost-effective at standard UK thresholds. To assess the cost-effectiveness of SCID screening for the NSC, a decision-tree model with lifetable estimates of outcomes was built. Model structure and parameterisation were informed by systematic review and expert clinical judgment. A public service perspective was used and lifetime costs and quality-adjusted life years (QALYs) were discounted at 3.5%. Probabilistic, one-way sensitivity analyses and an exploratory disbenefit analysis for the identification of non-SCID patients were conducted. Screening for SCID was estimated to result in an incremental cost-effectiveness ratio (ICER) of £18,222 with a reduction in SCID mortality from 8.1 (5–12) to 1.7 (0.6–4.0) cases per year of screening. Results were sensitive to a number of parameters, including the cost of the screening test, the incidence of SCID and the disbenefit to the healthy at birth and false-positive cases. Screening for SCID is likely to be cost-effective at £20,000 per QALY, key uncertainties relate to the impact on false positives and the impact on the identification of children with non-SCID T Cell lymphopenia.

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Milk Powder Fortified with Potassium and Phytosterols to Decrease the Risk of Cardiovascular Events among the Adult Population in Malaysia: A Cost-Effectiveness Analysis

Nutrients ◽

10.3390/nu11061235 ◽

2019 ◽

Vol 11 (6) ◽

pp. 1235

Author(s):

Anita E. Gandola ◽

Livia Dainelli ◽

Diane Zimmermann ◽

Maznah Dahlui ◽

Patrick Detzel

Keyword(s):

Cost Effectiveness ◽

Adult Population ◽

Grey Literature ◽

Milk Powder ◽

Cost Effective ◽

Sensitivity Analyses ◽

Base Case ◽

Discounted Cost ◽

Life Years ◽

The Impact

This study evaluated the cost-effectiveness of the consumption of a milk powder product fortified with potassium (+1050.28 mg/day) and phytosterols (+1200 mg/day) to lower systolic blood pressure and low-density lipoprotein cholesterol, respectively, and, therefore, the risk of myocardial infarction (MI) and stroke among the 35–75-year-old population in Malaysia. A Markov model was created against a do-nothing option, from a governmental perspective, and with a time horizon of 40 years. Different data sources, encompassing clinical studies, practice guidelines, grey literature, and statistical yearbooks, were used. Sensitivity analyses were performed to evaluate the impact of uncertainty on the base case estimates. With an incremental cost-effectiveness ratio equal to international dollars (int$) 22,518.03 per quality-adjusted life-years gained, the intervention can be classified as very cost-effective. If adopted nationwide, it would help prevent at least 13,400 MIs, 30,500 strokes, and more than 10,600 and 17,100 MI- and stroke-related deaths. The discounted cost savings generated for the health care system by those who consume the fortified milk powder would amount to int$8.1 per person, corresponding to 0.7% of the total yearly health expenditure per capita. Sensitivity analyses confirmed the robustness of the results. Together with other preventive interventions, the consumption of milk powder fortified with potassium and phytosterols represents a cost-effective strategy to attenuate the rapid increase in cardiovascular burden in Malaysia.

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Prenatal Zinc and Vitamin A Reduce the Benefit of Iron on Maternal Hematologic and Micronutrient Status at Delivery in Tanzania

Journal of Nutrition ◽

10.1093/jn/nxz242 ◽

2019 ◽

Vol 150 (2) ◽

pp. 240-248 ◽

Cited By ~ 1

Author(s):

Ramadhani A Noor ◽

Ajibola I Abioye ◽

Anne Marie Darling ◽

Ellen Hertzmark ◽

Said Aboud ◽

...

Keyword(s):

Vitamin A ◽

Pregnant Women ◽

Iron Supplementation ◽

Iron Status ◽

Zinc Protoporphyrin ◽

Plasma Zinc ◽

Vitamin A Supplementation ◽

Iron Supplements ◽

Micronutrient Status ◽

Increased Risk

ABSTRACT Background Zinc and vitamin A supplementation have both been shown to affect iron status, hemoglobin (Hb) concentration, and anemia in animal and human studies. However, evidence on their combined use in pregnancy, in the context of iron–folic acid (IFA) supplementation, remains limited. Objective This study determined the effects of prenatal zinc, vitamin A, and iron supplementation on maternal hematologic and micronutrient status at delivery in Tanzania. Methods We analyzed 2 large randomized controlled trials, using generalized estimating equations, and examined the effect of daily zinc (25 mg) and vitamin A (2500 IU) supplementation starting in the first trimester of pregnancy compared with placebo (n = 2500), and separately evaluated the safety and efficacy of daily iron (60 mg) supplementation among iron-replete pregnant women (n = 1500). Blood samples from baseline and delivery were tested for Hb, serum ferritin, soluble transferrin receptor, plasma zinc, and zinc protoporphyrin. Results Zinc and vitamin A supplementation were associated with lower Hb concentrations at delivery of −0.26 g/dL (95% CI: −0.50, −0.02 g/dL) and −0.25 g/dL (95% CI: −0.49, −0.01 g/dL), respectively. Vitamin A increased mean ferritin concentrations at delivery (14.3 μg/L, 95% CI: 1.84, 29.11 μg/L), but was associated with increased risk of severe anemia (RR: 1.41; 95% CI: 1.06, 1.88). Among women who were iron replete at baseline, iron supplementation reduced the risk of iron depletion at delivery by 47% (RR: 0.53; 95% CI: 0.43, 0.65). There was no effect of zinc or iron supplements on plasma zinc concentrations. Conclusions Our findings support existing WHO guidelines on prenatal iron, vitamin A, and zinc supplementation among pregnant women. In this setting, scaling uptake of prenatal iron supplements is warranted, but prenatal zinc and vitamin A supplementation did not benefit maternal hematologic status at delivery. In settings where vitamin A deficiency is endemic, the efficacy and safety of the WHO recommended prenatal vitamin A supplementation require further evaluation.

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Cost-effectiveness and budget impact of the microprocessor-controlled knee C-Leg in transfemoral amputees with and without diabetes mellitus

The European Journal of Health Economics ◽

10.1007/s10198-019-01138-y ◽

2020 ◽

Vol 21 (3) ◽

pp. 437-449 ◽

Cited By ~ 1

Author(s):

Alexander Kuhlmann ◽

Henning Krüger ◽

Susanne Seidinger ◽

Andreas Hahn

Keyword(s):

Diabetes Mellitus ◽

Cost Effectiveness ◽

Budget Impact ◽

Input Parameter ◽

Cost Effective ◽

Sensitivity Analyses ◽

Decision Analytic Model ◽

Life Years ◽

Transfemoral Amputees ◽

The Impact

Abstract Background The safe use of a prosthesis in activities of daily living is key for transfemoral amputees. However, the number of falls varies significantly between different prosthetic device types. This study aims to compare medical and economic consequences of falls in transfemoral amputees who use the microprocessor-controlled knee joint C-Leg with patients who use non-microprocessor-controlled (mechanical) knee joints (NMPK). The main objectives of the analysis are to investigate the cost-effectiveness and budget impact of C-Legs in transfemoral amputees with diabetes mellitus (DM) and without DM in Germany. Methods A decision-analytic model was developed that took into account the effects of prosthesis type on the risk of falling and fall-related medical events. Cost-effectiveness and budget impact analyses were performed separately for transfemoral amputees with and without DM. The study took the perspective of the statutory health insurance (SHI). Input parameters were derived from the published literature. Univariate and probabilistic sensitivity analyses (PSA) were performed to investigate the impact of changes in individual input parameter values on model outcomes and to explore parameter uncertainty. Results C-Legs reduced the rate of fall-related hospitalizations from 134 to 20 per 1000 person years (PY) in amputees without DM and from 146 to 23 per 1000 PY in amputees with DM. In addition, the C-Leg prevented 15 or 14 fall-related death per 1000 PY. Over a time horizon of 25 years, the incremental cost-effectiveness ratio (ICER) was 16,123 Euro per quality-adjusted life years gained (QALY) for amputees without DM and 20,332 Euro per QALY gained for amputees with DM. For the period of 2020–2024, the model predicted an increase in SHI expenditures of 98 Mio Euro (53 Mio Euro in prosthesis users without DM and 45 Mio Euro in prosthesis users with DM) when all new prosthesis users received C-Legs instead of NMPKs and 50% of NMPK user whose prosthesis wore out switched to C-Legs. Results of the PSA showed moderate uncertainty and a probability of 97–99% that C-Legs are cost-effective at an ICER threshold of 40,000 Euro (≈ German GDP per capita in 2018) per QALY gained. Conclusion Results of the study suggest that the C-Leg provides substantial additional health benefits compared with NMPKs and is likely to be cost-effective in transfemoral amputees with DM as well as in amputees without DM at an ICER threshold of 40,000 Euro per QALY gained.

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