Cost-effectiveness of age-related macular degeneration study supplements in the UK: combined trial and real-world outcomes data.

AIMS: To evaluate the cost-effectiveness of Age-Related Eye Disease Study (AREDS) 1 & 2 supplements in patients with either bilateral intermediate age-related macular degeneration, AREDS category 3, or unilateral neovascular age-related macular degeneration AMD (nAMD), AREDS category 4. METHODS: A patient-level health state transition model based on levels of visual acuity in the better-seeing eye was constructed to simulate the costs and consequences of patients taking AREDS vitamin supplements. SETTING: UK National Health Service (NHS). The model was populated with data from AREDS and real-world outcomes and resource use from a prospective multicentre national nAMD database study containing 92 976 ranibizumab treatment episodes. INTERVENTIONS: Two treatment approaches were compared: immediate intervention with AREDS supplements or no supplements. MAIN OUTCOME MEASURES: quality-adjusted life years (QALYs) and healthcare costs were accrued for each strategy, and incremental costs and QALYs were calculated for the lifetime of the patient. One-way and probabilistic sensitivity analyses were employed to test the uncertainty of the model. RESULTS: For AREDS category 3, the incremental cost-effectiveness ratio was £30 197. For AREDS category 4 compared with no intervention, AREDS supplements are more effective (10.59 vs 10.43 QALYs) and less costly (£52 074 vs 54 900) over the lifetime of the patient. CONCLUSIONS: The recommendation to publicly fund AREDS supplements to category 3 patients would depend on the healthcare system willingness to pay. In contrast, initiating AREDS supplements in AREDS category 4 patients is both cost saving and more effective than no supplement use and should therefore be considered in public health policy.

Cost-effectiveness of a disease-specific oral nutritional support for pressure ulcer healing.

BACKGROUND & AIMS: The Oligo Element Sore Trial has shown that supplementation with a disease-specific nutritional formula enriched with arginine, zinc, and antioxidants improves pressure ulcer (PU) healing in malnourished patients compared to an isocaloric-isonitrogenous support. However, the use of such a nutritional formula needs to be supported also by a cost-effectiveness evaluation. METHODS: This economic evaluation - from a local healthcare system perspective - was conducted alongside a multicenter, randomized, controlled trial following a piggy-back approach. The primary efficacy endpoint was the percentage of change in PU area at 8 weeks. The cost analysis focused on: the difference in direct medical costs of local PU care between groups and incremental cost-effectiveness ratio (ICER) of nutritional therapy related to significant study endpoints (percentage of change in PU area and ≥40% reduction in PU area at 8 weeks). RESULTS: Although the experimental formula was more expensive (mean difference: 39.4 Euros; P < 0.001), its use resulted in money saving with respect to both non-nutritional PU care activities (difference, -113.7 Euros; P = 0.001) and costs of local PU care (difference, -74.3 Euros; P = 0.013). Therefore, given its efficacy it proved to be a cost-effective intervention. The robustness of these results was confirmed by the sensitivity analyses. CONCLUSION: The use of a disease-specific oral nutritional formula not only results in better healing of PUs, but also reduces the costs of local PU care from a local healthcare system perspective.

Economic costs to caregivers of diarrhoea treatment among children below 5 in rural Gujarat India: findings from an external evaluation of the DAZT programme.

INTRODUCTION: Diarrhoea is a leading cause of mortality among young children in India although few receive the recommended treatment. The diarrhoea alleviation through zinc and oral rehydration salts (ORS) therapy (DAZT) team initiated a programme in Gujarat from 2011 to 2013 to increase coverage of these interventions through public and private providers at scale. This study evaluates the economic impact of diarrhoea to caregivers before and after the introduction of zinc and ORS at scale through the DAZT programme. METHODS: The DAZT programme evaluation took a before-and-after study design using a two-stage clustered cross-sectional survey. Factors associated with the odds of caregivers incurring economic costs and their amounts were evaluated in a two-part modelling approach. RESULTS: The DAZT programme lowered unadjusted economic costs to caregivers of treating a diarrhoeal episode from $4.04 to $2.49 in 2 years. Controlling for covariates, analysis showed no association between the programme and a change in odds of incurring an economic cost but did show an association with a reduction in economic cost of $2.15 (95% confidence interval (CI) $1.20-$3.11) per diarrhoea episode. A more than 4-fold increase in care-seeking from public community health workers, reduction in care-seeking from higher levels of the health system and reduced spending on drugs besides ORS and zinc may explain these results. DISCUSSION: This study found an association between zinc introduction and a reduction in economic burden of diarrhoea treatment to caregivers in underserved rural areas of Gujarat through more efficient patterns of care-seeking and content of care.

Cost-effectiveness of anti-oxidant vitamins plus zinc treatment to prevent the progression of intermediate age-related macular degeneration. A Singapore perspective.

PURPOSE: To determine if providing high dose anti-oxidant vitamins and zinc treatment age-related eye disease study (AREDS formulation) to patients with intermediate age-related macular degeneration (AMD) aged 40-79 years from Singapore is cost-effective in preventing progression to wet AMD. METHODS: A hypothetical cohort of category 3 and 4 AMD patients from Singapore was followed for 5 calendar years to determine the number of patients who would progress to wet AMD given the following treatment scenarios: (a) AREDS formulation or placebo followed by ranibizumab (as needed) for wet AMD. (b) AREDS formulation or placebo followed by bevacizumab (monthly) for wet AMD. (c) AREDS formulation or placebo followed by aflibercept (VIEW I and II trial treatment regimen). Costs were estimated for the above scenarios from the providers' perspective, and cost-effectiveness was measured by cost per disability-adjusted life year (DALY) averted with a disability weight of 0.22 for wet AMD. The costs were discounted at an annual rate of 3%. RESULTS: Over 5400 patients could be prevented from progressing to wet AMD cumulatively if AREDS formulation were prescribed. AREDS formulation followed by ranibizumab was cost-effective compared to placebo-ranibizumab or placebo-aflibercept combinations (cost per DALY averted: SGD$23,662.3 and SGD$21,138.8, respectively). However, bevacizumab (monthly injections) alone was more cost-effective compared to AREDS formulation followed by bevacizumab. CONCLUSION: Prophylactic treatment with AREDS formulation for intermediate AMD patients followed by ranibizumab or for patients who progressed to wet AMD was found to be cost-effective. These findings have implications for intermediate AMD screening, treatment and healthcare planning in Singapore.

Cost-effectiveness analysis of zinc supplementation for treatment of acute diarrhea in children younger than 5 years in Colombia.

OBJECTIVE: The objective of this study was to determine the cost-effectiveness of zinc supplementation for the treatment of acute diarrhea (AD) in children younger than 5 years in Colombia. METHODS: The cost-effectiveness analysis was performed from the perspective of the Colombian health system. The standard treatment with the addition of zinc was compared with the standard treatment without zinc in children younger than 5 years. The time horizon was 1 month. Effectiveness was extracted from a systematic review of literature. The specific data for Colombia were taken from local databases and observational studies. To determine the costs, a typical case was constructed by reviewing guidelines and medical records and validated by experts. To evaluate the resources consumed, Colombian tariff manuals were used. Costs were stated in Colombian pesos (COP) and US dollar (USD) for 2010. Deterministic sensitivity analysis was performed to evaluate the impact of changes in cost and effectiveness of the strategies on the results from the model. RESULTS: The results from the model indicate that zinc supplementation is a dominant strategy; it is less costly and more effective than standard treatment without zinc (reduction of $15,210 COP [8.14 USD] per child). The results are sensitive to changes in the probability of hospitalization and of persistent diarrhea. CONCLUSIONS: Zinc for the treatment of AD is a highly cost-effective strategy and is recommended for inclusion in the benefit plan of the Colombian health system. This intervention is more cost-effective in children with a higher risk of persistent diarrhea and hospitalization.

Cost of childhood diarrhoea in rural South Africa: exploring cost-effectiveness of universal zinc supplementation.

OBJECTIVE: To describe the cost of diarrhoeal illness in children aged 6-24 months in a rural South African community and to determine the threshold prevalence of stunting at which universal Zn plus vitamin A supplementation (VAZ) would be more cost-effective than vitamin A alone (VA) in preventing diarrhoea. DESIGN: We conducted a cost analysis using primary and secondary data sources. Using simulations we examined incremental costs of VAZ relative to VA while varying stunting prevalence. SETTING: Data on efficacy and societal costs were largely from a South African trial. Secondary data were from local and international published sources. SUBJECTS: The trial included children aged 6-24 months. The secondary data sources were a South African health economics survey and the WHO-CHOICE (CHOosing Interventions that are Cost Effective) database. RESULTS: In the trial, stunted children supplemented with VAZ had 2·04 episodes (95 % CI 1·37, 3·05) of diarrhoea per child-year compared with 3·92 episodes (95 % CI 3·02, 5·09) in the VA arm. Average cost of illness was $Int 7·80 per episode (10th, 90th centile: $Int 0·28, $Int 15·63), assuming a minimum standard of care (oral rehydration and 14 d of therapeutic Zn). In simulation scenarios universal VAZ had low incremental costs or became cost-saving relative to VA when the prevalence of stunting was close to 20 %. Incremental cost-effectiveness ratios were sensitive to the cost of intervention and coverage levels. CONCLUSIONS: This simulation suggests that universal VAZ would be cost-effective at current levels of stunting in parts of South Africa. This requires further validation under actual programmatic conditions.

Caretakers' perception towards using zinc to treat childhood diarrhoea in rural western Kenya.

Zinc treatment for diarrhoea can shorten the course and prevent future episodes among children worldwide. However, knowledge and acceptability of zinc among African mothers is unknown. We identified children aged 3 to 59 months, who had diarrhoea within the last three months and participated in a home-based zinc treatment study in rural Kenya. Caretakers of these children were enrolled in two groups; zinc-users and non-users. A structured questionnaire was administered to all caretakers, inquiring about knowledge and appropriate use of zinc. Questions on how much the caretakers were willing to pay for zinc were asked. Proportions were compared using Mantel-Haenszel test, and medians were compared using Wilcoxon Rank Sum test. Among 109 enrolled caretakers, 73 (67%) used zinc, and 36 (33%) did not. Sixty-four (88%) caretakers in zinc-user group reported satisfaction with zinc treatment. Caretakers in the zinc-user group more often correctly identified appropriate zinc treatment (98%-100%) than did those in the non-user group (64-72%, p<0.001). Caretakers in the zinc-user group answered more questions about zinc correctly or favourably (median 10 of 11) compared to those in the non-user group (median 6.3 of 11, p<0.001). Caretakers in the zinc-user group were willing to pay more for a course of zinc in the future than those in the non-user group (median US$ 0.26, p<0.001). Caretakers of children given zinc recently had favourable impressions on the therapy and were willing to pay for it in the future. Active promotion of zinc treatment in clinics and communities in Africa could lead to greater knowledge, acceptance, and demand for zinc.

Using nanostructured conductive carbon tape modified with bismuth as the disposable working electrode for stripping analysis in paper-based analytical devices.

Low cost disposable working electrodes are specifically desired for practical applications of electrochemical detection considering maturity of electrochemical stations and data collection protocols. In this paper double-sided conductive adhesive carbon tape with nanostructure was applied to fabricate disposable working electrodes. Being supported by indium tin oxide glass, the prepared carbon tape electrodes were coated with bismuth film for stripping analysis of heavy metal ions. By integrating the bismuth modified electrodes with paper-based analytical devices, we were able to differentiate Zn, Cd and Pb ions with the sample volume of around 15 µL. After the optimization of parameters, including modification of bismuth film and the area of the electrodes, etc., Pb ions could be measured in the linear range from 10 to 500 µg/L with the detection limit of 2 µg/L. Our experimental results revealed that the disposable modified electrodes could be used to quantify migrated lead from toys with the results agreed well with that using atomic absorption spectrometry. Although bismuth modification and stripping analysis could be influenced by the low conductivity of the carbon tape, the low cost disposable carbon tape electrodes take the advantages of large-scaled produced double-sided carbon tape, including its reproducible nanostructure and scaled-up fabrication process. In addition, the preparation of disposable electrodes avoids time-consuming pretreatment and experienced operation. This study implied that the carbon tape might be an alternative candidate for practical applications of electrochemical detection.

Zinc-pheophorbide a-highly efficient low-cost photosensitizer against human adenocarcinoma in cellular and animal models.

BACKGROUND: Our previous study has shown a prolonged retention and accumulation of Zn-pheophorbide a, a water-soluble derivative of chlorophyll a, in tumor tissue (Szczygiel et al. [19]). This prompted us to further evaluate the phototherapeutic potential of this photosensitizer of excellent physicochemical properties. METHODS: Cellular uptake of Zn-pheophorbide, its localization in cells, cytotoxicity, phototoxicity and cell death mechanisms were studied in human adenocarcinoma cell lines: A549, MCF-7 and LoVo. The PDT efficacy was tested against A549 tumors growing in nude mice. RESULTS: Zn-pheophorbide a even at very low concentrations (∼1×10(-6)M) and at low light doses (5J/cm(2)) causes a strong photodynamic effect, leading to 100% cell mortality. Confocal microscopy showed that in contrast to most derivatives of chlorophyll, Zn-pheophorbide a does not localize to mitochondria. The photodynamic effects and the cell death mechanisms of Zn-pheophorbide a, its Mg analog (chlorophyllide a) and Photofrin were compared on the A549 cells. Zn-pheophorbide a showed the strongest photodynamic effect, at low dose killing all A549 cells via apoptosis and necrosis. The very high anti-cancer potential of Zn-pheophorbide was confirmed in a photodynamic treatment of the A549 tumors. They either regressed or were markedly inhibited for up to 4 months after the treatment, resulting, on average, in a 5-fold decrease in tumor volume. CONCLUSION: These results show that Zn-pheophorbide a is a very promising low-cost, synthetically easily accessible, second generation photosensitizer against human cancer.

Indian social safety net programs as platforms for introducing wheat flour fortification: a case study of Gujarat, India.

BACKGROUND: Micronutrient deficiencies exact an enormous health burden on India. The release of the National Family Health Survey results--showing the relatively wealthy state of Gujarat having deficiency levels exceeding national averages--prompted Gujarat officials to introduce fortified wheat flour in their social safety net programs (SSNPs). OBJECTIVE: To provide a case study of the introduction of fortified wheat flour in Gujarat's Public Distribution System (PDS), Integrated Child Development Scheme (ICDS), and Mid-Day Meal (MDM) Programme to assess the coverage, costs, impact, and cost-effectiveness of the initiative. METHODS: India's 2004/05 National Sample Survey data were used to identify beneficiaries of each of Gujarat's three SSNPs and to estimate usual intake levels of vitamin A, iron, and zinc. Comparing age- and sex-specific usual intakes to Estimated Average Requirements, the proportion of the population with inadequate intakes was estimated. Postfortification intake levels and reductions in inadequate intake were estimated. The incremental cost of fortifying wheat flour and the cost-effectiveness of each program were estimated. RESULTS: When each program was assessed independently, the proportion of the population with inadequate vitamin A intakes was reduced by 34% and 74% among MDM and ICDS beneficiaries, respectively. Both programs effectively eliminated inadequate intakes of both iron and zinc. Among PDS beneficiaries, the proportion with inadequate iron intakes was reduced by 94%. CONCLUSIONS. Gujarat's substitution of fortified wheat flour for wheat grain is dramatically increasing the intake of micronutrients among its SSNP beneficiaries. The incremental cost of introducing fortification in each of the programs is low, and, according to World Health Organization criteria, each program is "highly cost-effective." The introduction of similar reforms throughout India would largely eliminate the inadequate iron intake among persons participating in any of the three SSNPs and would have a significant impact on the global prevalence rate of inadequate iron intake.

Willingness to pay for zinc treatment of childhood diarrhoea in a rural population of Bangladesh.

INTRODUCTION: Young children in the developing world continue to experience a median of between two and four episodes of diarrhoea each year. To better understand adherence to the WHO/UNICEF-recommended diarrhoea management guidelines, which now include zinc, this study aimed to determine how much caregivers were willing to pay for zinc treatment and to explore the characteristics of actual users of zinc in a rural community of Bangladesh. METHODS: Initially we conducted a contingent valuation survey among primary caregivers of children aged 6-36 months. We assessed their willingness-to-pay (WTP) for 10 days of zinc treatment per diarrhoea episode at Tk.15 (US$0.26) and at Tk.20 (US$0.34), followed by an open question on the highest WTP amount. Next we conducted a cross-sectional survey in the same area to identify households with children who had received zinc during their most recent diarrhoea episode within the previous 3 months. RESULTS: Field workers interviewed 111 primary caregivers to explore WTP for zinc in childhood diarrhoea. Of these, 92% were willing to pay US$0.26 and 85% of these positive respondents were also willing to pay US$0.34. The mean WTP was US$0.50. We found that higher socio-economic status, better educated fathers and lower mother's age positively influenced the expressed WTP. Actual users, the 51 households whose child received zinc in their most recent diarrhoea episode, were more likely to have educated parents, higher socio-economic status and to have sought care from qualified providers for diarrhoeal illness. CONCLUSION: The expressed WTP results indicate a high demand for zinc in childhood diarrhoea management in this rural community of Bangladesh. Safety net measures and targeted communication activities specifically aimed at the poor and less educated population could be beneficial to achieve more equitable use of zinc as part of the standard treatment with oral rehydration solution in childhood diarrhoea management.

The impact of rapid economic growth and globalization on zinc nutrition in South Korea.

OBJECTIVE: Zn deficiency may be widespread in Asian countries such as South Korea. However, dietary habits have changed in response to rapid economic growth and globalization. Zn nutrition in South Koreans has therefore been assessed during a period (1969-1998) of unprecedented economic growth. DESIGN AND METHODS: Cross-sectional food consumption data from the Korean National Nutrition Survey Reports (KNNSR) of South Korea at four separate time points (1969, 1978, 1988 and 1998) were used to calculate Zn, Ca and phytate intakes using various food composition tables, databases and literature values. Nutrient values in local foods were cited from their analysed values. RESULTS: Average Zn intake was 5.8, 4.8 and 5.3 mg/d for 1969, 1978 and 1988 respectively, increasing to 7.3 mg/d in 1998 (73 % of the Korean Dietary Reference Intake). The phytate:Zn molar ratio decreased from 21 to 8 during the study period. Dietary Zn depletion due to marked decreases in cereal consumption, particularly barley which has a low Zn bioavailability, was counterbalanced by marked increases in the consumption of meat and fish, which are also Zn-rich foods. Reduced phytate consumption coincident with increased Zn intake suggests that Zn bioavailability also improved, particularly by 1998. CONCLUSIONS: Although total Zn intake was not greatly affected over the initial period of economic growth in South Korea (1969-1988), Zn contributions from different food sources changed markedly and both Zn intake and potential bioavailability were improved by 1998. The study may have implications for Zn nutrition in other Asian countries currently experiencing rapid economic growth.

Cost-effectiveness of vitamin therapy for age-related macular degeneration.

OBJECTIVE: To determine the cost-effectiveness of vitamin therapy (antioxidants plus zinc) for all indicated patients diagnosed with age-related macular degeneration (AMD). DESIGN: We compared the impacts of vitamin therapy with those of no vitamin therapy using a computerized, stochastic, agent-based model. The model simulated the natural history of AMD and patterns of ophthalmic service use in the United States in a cohort from age 50 years until 100 or death. PARTICIPANTS AND/OR CONTROLS: The model created 20 million simulated individuals. These individuals each received both the intervention (vitamin therapy after diagnosis) and the control (no vitamin therapy). Expected outcomes generated when vitamins were taken after diagnosis were compared with the expected outcomes generated when they were not. METHODS: The model created individuals representative of patients in the U.S. Incidence of early AMD was based on published studies, as was vision loss and response to choroidal neovascularization therapies. Post-incident disease progression was governed by previously unpublished data drawn from the Age-Related Eye Disease Study. MAIN OUTCOME MEASURES: Extent of disease progression, years and severity of visual impairment, cost of ophthalmic care and nursing home services, and quality-adjusted life years (QALYs). Costs and benefits were considered from the health care perspective and discounted using a 3% rate. The analysis was run for 50 years starting in 2003. RESULTS: Compared with no therapy, vitamin therapy yielded a cost-effectiveness ratio of $21,387 per QALY gained and lowered the percentage of patients with AMD who ever developed visual impairment in the better-seeing eye from 7.0% to 5.6%. CONCLUSIONS: Our model demonstrates that vitamin therapy for AMD improves quality of life at a reasonable cost.

The influence of metal source uncertainty on cost-effective allocation of mine water pollution abatement in catchments.

In mine water pollution abatement, it is commonly assumed that known mine waste sites are the major pollution sources, thus neglecting the possibility of significant contribution from other old and diffuse sources within a catchment. We investigate the influence of different types of pollution source uncertainty on cost-effective allocation of abatement measures for mine water pollution. A catchment-scale cost-minimization model is developed and applied to the catchment of the river Dalälven, Sweden, in order to exemplify important effects of such source uncertainty. Results indicate that, if the pollution distribution between point and diffuse sources is partly unknown, downstream abatement measures, such as constructed wetlands, at given compliance boundaries are often cost-effective. If downstream abatement measures are not practically feasible, the pollution source distribution between point and diffuse mine water sources is critical for cost-effective solutions to abatement measure allocation in catchments. In contrast, cost-effective solutions are relatively insensitive to uncertainty in total pollutant discharge from mine water sources.

Cost-effectiveness of zinc as adjunct therapy for acute childhood diarrhoea in developing countries.

OBJECTIVE: To analyse the incremental costs, effects and cost-effectiveness of zinc used as adjunct therapy to standard treatment of acute childhood diarrhoea, including dysentery, and to reassess the cost-effectiveness of standard case management with oral rehydration salt (ORS). METHODS: A decision tree was used to model expected clinical outcomes and expected costs under four alternative treatment strategies. The best available epidemiological, clinical and economic evidence was used in the calculations, and the United Republic of Tanzania was the reference setting. Probabilistic cost-effectiveness analysis was performed using a Monte-Carlo simulation technique and the potential impacts of uncertainty in single parameters were explored in one-way sensitivity analyses. FINDINGS: ORS was found to be less cost-effective than previously thought. The use of zinc as adjunct therapy significantly improved the cost-effectiveness of standard management of diarrhoea for dysenteric as well as non-dysenteric illness. The results were particularly sensitive to mortality rates in non-dysenteric diarrhoea, but the alternative interventions can be defined as highly cost-effective even in pessimistic scenarios. CONCLUSION: There is sufficient evidence to recommend the inclusion of zinc into standard case management of both dysenteric and non-dysenteric acute diarrhoea.A direct transfer of our findings from the United Republic of Tanzania to other settings is not justified, but there are no indications of large geographical differences in the efficacy of zinc. It is therefore plausible that our findings are also applicable to other developing countries.

Cost utility of screening and treatment for early age related macular degeneration with zinc and antioxidants.

AIM: To assess the cost effectiveness of high dose zinc and antioxidants for delaying and reducing the progression of early age related macular degeneration (AMD). BACKGROUND: AMD is the leading cause of severe vision impairment and blindness in older people throughout the developed world. It currently affects around 420 000 people in the United Kingdom. METHODS: A cost utility analysis (CUA) was conducted to estimate the cost per quality adjusted life year (QALY) for screening a cohort of men and women, aged 55 years and over, for early AMD and then treating them with zinc and antioxidants. The incremental CUA was based on a decision analytic model, comparing screening with a no screening comparator (current practice). Extensive one way sensitivity analysis of parameters was conducted to determine the robustness of the model. RESULTS: In this model the cost effectiveness of screening for early AMD was pound 22 722 per quality adjusted life year (QALY) saved. The cost per QALY decreased to pound 18 948 if photodynamic therapy with verteporfin savings were included. CONCLUSIONS: Screening for, and prophylactic treatment of, early AMD is estimated to cost around pound 22 700 per QALY saved. This cost falls within accepted levels to warrant further investigation. These findings have implications for ophthalmic practice and healthcare planning.

Effect of zinc supplementation on clinical course of acute diarrhoea.

This report summarizes the current knowledge on the effects of zinc supplementation on the management of acute diarrhoea. All published and unpublished studies on this topic, conducted in hospitals and in the community, were reviewed. Based on the results of this review, it is concluded that there is now enough evidence demonstrating the efficacy of zinc supplementation on the clinical course of diarrhoea, with regard to the severity and duration of the episode. However, the meeting also concluded that effectiveness studies to assess the feasibility, sustainability, and cost-effectiveness of different strategies for delivering zinc supplementation should be undertaken.