Cost-effectiveness of a canine visceral leishmaniasis control program in Brazil based on insecticide-impregnated collars.

INTRODUCTION: The use of insecticide-impregnated dog collars is a potentially useful tool for the control of visceral leishmaniasis. The objective of the present study was to perform a cost-effectiveness analysis of a program based on insecticide-impregnated collars compared to traditional visceral leishmaniasis control strategies used in Brazil. METHODS: A cost-effectiveness analysis was performed from the perspective of the Unified Health System, using data from the Visceral Leishmaniasis Control Program implemented in the municipality of Montes Claros, Minas Gerais. The direct costs of the three control strategies, which were 1) canine infection screening + sacrifice, 2) residual chemical control of the vector, and 3) insecticide-impregnated dog collars (Scalibor®), were evaluated over the two-year study period. RESULTS: The total cost of the program in the area subjected to the traditional control strategies (strategies 1 and 2; control area) was R$ 1,551,699.80, and in the area subjected to all three control strategies (intervention area), it was R$ 1,898,190.16. The collar program was considered highly cost-effective at preventing canine visceral leishmaniasis (incremental cost-effectiveness ratio of approximately R$ 578 per avoided dog sacrifice). CONCLUSIONS: These results provide support for the decision by the Brazilian Ministry of Health in 2019 to provide insecticide-impregnated collars for the control of canine visceral leishmaniasis in a pilot project.

Cost-effectiveness of a canine visceral leishmaniasis control program in Brazil based on insecticide-impregnated collars

Abstract INTRODUCTION: The use of insecticide-impregnated dog collars is a potentially useful tool for the control of visceral leishmaniasis. The objective of the present study was to perform a cost-effectiveness analysis of a program based on insecticide-impregnated collars compared to traditional visceral leishmaniasis control strategies used in Brazil. METHODS: A cost-effectiveness analysis was performed from the perspective of the Unified Health System, using data from the Visceral Leishmaniasis Control Program implemented in the municipality of Montes Claros, Minas Gerais. The direct costs of the three control strategies, which were 1) canine infection screening + sacrifice, 2) residual chemical control of the vector, and 3) insecticide-impregnated dog collars (Scalibor®), were evaluated over the two-year study period. RESULTS: The total cost of the program in the area subjected to the traditional control strategies (strategies 1 and 2; control area) was R$ 1,551,699.80, and in the area subjected to all three control strategies (intervention area), it was R$ 1,898,190.16. The collar program was considered highly cost-effective at preventing canine visceral leishmaniasis (incremental cost-effectiveness ratio of approximately R$ 578 per avoided dog sacrifice). CONCLUSIONS: These results provide support for the decision by the Brazilian Ministry of Health in 2019 to provide insecticide-impregnated collars for the control of canine visceral leishmaniasis in a pilot project.

Efficacy of endoscopic treatments for acute esophageal variceal bleeding in cirrhotic patients: systematic review and meta-analysis.

Background and aim Guidelines recommend use of ligation and vasoactive drugs as first-line therapy and as grade A evidence for acute variceal bleeding (AVB), although Western studies about this issue are lacking. Methods We performed a systematic review and meta-analysis of randomized controlled trials (RCT) to evaluate the efficacy of endoscopic treatments for AVB in patients with cirrhosis. Trials that included patients with hepatocellular carcinoma, use of portocaval shunts or esophageal resection, balloon tamponade as first bleeding control measure, or that received placebo or elective treatment in one study arm were excluded. Results A total of 8382 publications were searched, of which 36 RCTs with 3593 patients were included. Ligation was associated with a significant improvement in bleeding control (relative risk [RR] 1.08; 95 % confidence interval [CI] 1.02 - 1.15) when compared to sclerotherapy. Sclerotherapy combined with vasoactive drugs showed higher efficacy in active bleeding control compared to sclerotherapy alone (RR 1.17; 95 % CI 1.10 - 1.25). The combination of ligation and vasoactive drugs was not superior to ligation alone in terms of overall rebleeding (RR 2.21; 95 %CI 0.55 - 8.92) and in-hospital mortality (RR 1.97; 95 %CI 0.78 - 4.97). Other treatments did not generate meta-analysis. Conclusions This study showed that ligation is superior to sclerotherapy, although with moderate heterogeneity. The combination of sclerotherapy and vasoactive drugs was more effective than sclerotherapy alone. Although current guidelines recommend combined use of ligation with vasoactive drugs in treatment of esophageal variceal bleeding, this study failed to demonstrate the superiority of this combined treatment.

Cost-effectiveness analysis of diagnostic-therapeutic strategies for visceral leishmaniasis in Brazil.

INTRODUCTION: Visceral leishmaniasis (VL) is fatal if not diagnosed and treated. This study aimed to estimate the cost-effectiveness of diagnostic-therapeutic alternatives for VL in Brazil. METHODS: A decision model estimated the life expectancy and costs of six diagnostic-therapeutic strategies. RESULTS: IT LEISH + liposomal amphotericin B emerged the best option, presenting lower costs and higher effectiveness. DAT-LPC + liposomal amphotericin B showed an incremental cost-effectiveness ratio of US$ 326.31 per life year. CONCLUSIONS: These findings indicate the feasibility of incorporating DAT and designating liposomal amphotericin B as the first-line drug for VL in Brazil.

Efficacy of low-level laser for treatment of cancer oral mucositis: a systematic review and meta-analysis.

Review effectiveness of low-level laser therapy (LLLT) in the curative treatment of oral mucositis (OM) in patients receiving cancer therapy. A systematic review with meta-analysis was performed using Medline, Embase, and Cochrane Library databases according to PRISMA guidelines, to identify randomized controlled trials (RCT) on OM in patients during and/or after cancer therapy and in which the therapeutic approach was LLLT, with wavelengths between 632 and 970 nm. We considered grade of OM as a dichotomous variable (such as an improvement or not in severe OM on the seventh day of therapy), with the analysis of subgroups of adult patients or children and adolescents and as a continuous variable with determination of the time for the complete resolution and the subgroup analysis occurred with the strata of the samples by treatment only with chemotherapy or chemotherapy and radiotherapy. This paper's protocol was registered a priori at https://www.crd.york.ac.uk/PROSPERO . We found five RCT (total of 315 patients) with adequate methodology. LLLT was effective, presenting a 62% risk reduction of severe mucositis on the seventh day of evaluation (RR = 0.38 [95% CI, 0.19-0.75]). When we analyzed subgroups, RR was 0.28 (95% CI 0.17-0.46) in the adult studies and 0.90 (95% CI, 0.46-1.78) in the studies with children and adolescents. We demonstrated a mean reduction of 4.21 days in the time of complete resolution of OM (CI - 5.65 to - 2.76) in favor of LLLT. There is moderate evidence that LLLT is effective in resolving OM lesions in adult patients undergoing cancer therapy. LLLT demonstrates potential for decreasing the resolution time of OM lesions by approximately 4.21 days.

Performance of Cystatin C-Based Equations for Estimation of Glomerular Filtration Rate in Diabetes Patients: A Prisma-Compliant Systematic Review and Meta-Analysis.

The accuracy of estimated glomerular filtration rate (eGFR) equations in diabetes mellitus (DM) patients has been extensively questioned. We evaluated the performance of cystatin C-based equations alone or in combination with creatinine to estimate GFR in DM patients. A PRISMA-compliant systematic review was performed in the MEDLINE and Embase databases, with "diabetes mellitus" and "cystatin C" as search terms. Studies comparing cystatin C-based eGFR equations with measured GFR (mGFR) in DM patients were eligible. Accuracies P10, P15, P20, and P30 indicated the proportion of eGFR results within 10, 15, 20, and 30% of mGFR. Single-arm meta-analyses were conducted, and the Quality of Diagnostic Accuracy Studies-II tool (QUADAS-2) was applied. Twenty-three studies comprising 7065 participants were included, and 24 equations were analyzed in a broad range of GFRs. Meta-analyses were completed for 10 equations. The mean P30 accuracies of the equations ranged from 41% to 87%, with the highest values found with both CKD-EPI equations. Mean P10-P15 achieved 35% in the best scenario. A sensitivity analysis to evaluate different mGFR methods did not change results. In conclusion, cystatin C-based eGFR equations represent measured GFR fairly at best in DM patients, with high variability among the several proposed equations.

Cost-effectiveness analysis of diagnostic-therapeutic strategies for visceral leishmaniasis in Brazil

Abstract INTRODUCTION: Visceral leishmaniasis (VL) is fatal if not diagnosed and treated. This study aimed to estimate the cost-effectiveness of diagnostic-therapeutic alternatives for VL in Brazil. METHODS: A decision model estimated the life expectancy and costs of six diagnostic-therapeutic strategies. RESULTS: IT LEISH + liposomal amphotericin B emerged the best option, presenting lower costs and higher effectiveness. DAT-LPC + liposomal amphotericin B showed an incremental cost-effectiveness ratio of US$ 326.31 per life year. CONCLUSIONS: These findings indicate the feasibility of incorporating DAT and designating liposomal amphotericin B as the first-line drug for VL in Brazil.

Budgetary impact of diagnostic tests for visceral leishmaniasis in Brazil.

The aim of the present study was to estimate the financial costs of the incorporation and/or replacement of diagnostic tests for human visceral leishmaniasis (VL) in Brazil. The analysis was conducted from the perspective of the Brazilian Unified National Health System (SUS) over a period of three years. Six diagnostic tests were evaluated: the indirect immunofluorescence antibody test (IFAT), the IT LEISH rapid test, the parasitological examination of bone marrow aspirate, the direct agglutination test (DAT-LPC) standardized in the Clinical Research Laboratory, René Rachou Institute of the Oswaldo Cruz Foundation, the Kalazar Detect rapid test, and polymerase chain reaction (PCR). The assumptions used were the number of suspected cases of VL reported to the Brazilian Ministry of Health in 2014 and the direct cost of diagnostic tests. The costs to diagnose suspected cases of VL over three years using the IFAT and the DAT-LPC were estimated at USD 280,979.91 and USD 121,371.48, respectively. The analysis indicated that compared with the use of the IFAT, the incorporation of the DAT-LPC into the SUS would result in savings of USD 159,608.43. With regard to the budgetary impact of rapid tests, the use of IT LEISH resulted in savings of USD 21.708,72 over three years. Compared with a parasitological examination, diagnosis using PCR resulted in savings of USD 3,125,068.92 over three years. In this study, the replacement of the IFAT with the DAT-LPC proved financially advantageous. In addition, the replacement of the Kalazar Detect rapid test with the IT LEISH in 2015 was economically valuable, and the replacement of parasitological examination with PCR was indicated.

The direct costs of treating human visceral leishmaniasis in Brazil.

INTRODUCTION:: The drugs available for visceral leishmaniasis (VL) treatment in Brazil have specific characteristics in terms of operability, effectiveness, toxicity, and cost. The aim of this study was to estimate the direct costs of therapies recommended by the Ministry of Health (MH) for VL treatment in Brazil. METHODS:: The analytical perspective used was that adopted by the Brazilian Public Health System. Three drugs and four regimens were included: 1) N-methyl glucamine antimoniate intramuscularly at 20mg per kg per day for 30 days; 2) N-methyl glucamine antimoniate intravenously at 20mg per kg per day for 30 days; 3) amphotericin B deoxycholate at 1mg per kg per day for 21 days; and 4) liposomal amphotericin B at 3mg per kg per day for a 7 days treatment. RESULTS:: The estimated direct costs of treatment for an adult patient using N-methylglucamine antimoniate administered via the intramuscular and intravenous routes were USD 418.52 and USD 669.40, respectively. The estimated cost of treatment with amphotericin B deoxycholate was USD 1,522.70. Finally, the estimated costs of treatment with liposomal amphotericin B were USD 659.79, and USD 11,559.15 using the price adopted by the WHO and the Drug Regulation Board, respectively. CONCLUSIONS:: This analysis indicates the economic feasibility of replacing N-methyl glucamine antimoniate with liposomal amphotericin B, which allows a shorter treatment period with less toxicity compared with other treatments, provided that the purchase value used by the WHO and transferred to the MH is maintained.

The direct costs of treating human visceral leishmaniasis in Brazil

Abstract INTRODUCTION: The drugs available for visceral leishmaniasis (VL) treatment in Brazil have specific characteristics in terms of operability, effectiveness, toxicity, and cost. The aim of this study was to estimate the direct costs of therapies recommended by the Ministry of Health (MH) for VL treatment in Brazil. METHODS: The analytical perspective used was that adopted by the Brazilian Public Health System. Three drugs and four regimens were included: 1) N-methyl glucamine antimoniate intramuscularly at 20mg per kg per day for 30 days; 2) N-methyl glucamine antimoniate intravenously at 20mg per kg per day for 30 days; 3) amphotericin B deoxycholate at 1mg per kg per day for 21 days; and 4) liposomal amphotericin B at 3mg per kg per day for a 7 days treatment. RESULTS: The estimated direct costs of treatment for an adult patient using N-methylglucamine antimoniate administered via the intramuscular and intravenous routes were USD 418.52 and USD 669.40, respectively. The estimated cost of treatment with amphotericin B deoxycholate was USD 1,522.70. Finally, the estimated costs of treatment with liposomal amphotericin B were USD 659.79, and USD 11,559.15 using the price adopted by the WHO and the Drug Regulation Board, respectively. CONCLUSIONS: This analysis indicates the economic feasibility of replacing N-methyl glucamine antimoniate with liposomal amphotericin B, which allows a shorter treatment period with less toxicity compared with other treatments, provided that the purchase value used by the WHO and transferred to the MH is maintained.

Diretriz metodológica para estudos de avaliação econômica de tecnologias em saúde no Brasil / Methodological guidelines for economic evaluation studies of health technologies in Brazil

Objetivos: Resumir os principais pontos da Diretriz de Avaliação Econômica em Saúde (AES) do Ministério da Saúde. Métodos: As diretrizes para AES no Brasil foram desenvolvidas por intermédio de múltiplas rodadas de trabalho iterativas por grupo multidisciplinar de especialistas em economia da saúde e foram submetidas à consulta pública. Resultados: O problema deve ser definido por meio de uma questão de pesquisa estruturada. O estudo pode ser baseado em dados primários ou em modelagem, em que o primeiro aumenta a validade interna dos resultados e o segundo, a capacidade de generalização do estudo. Quando o trabalho for baseado em modelagem e focado em doença crônica, o modelo de Markov pode ser usualmente empregado, quando não houver necessidades que apontem para simulação de eventos discretos (como competição dos indivíduos por recursos escassos) ou modelos de transmissão dinâmica (em vacinação e/ou doenças infecciosas com alta transmissão entre indivíduos). O horizonte temporal preferencial é o de tempo de vida, e a taxa de desconto padrão é de 5% para custo e efetividade. Os custos devem representar a perspectiva do Sistema Único de Saúde (SUS), podendo ser estimados por macrocusteio ou microcusteio. Sempre que possível, os resultados devem ser apresentados no formato de custo por ano de vida salvo ajustado para qualidade, para facilitar comparações com outros estudos. Análises de sensibilidade devem ser extensamente empregadas, de forma a avaliar o impacto da incerteza nos resultados produzidos. Conclusões: Espera-se que, com a padronização da metodologia proposta na Diretriz, a produção de AES no país tenha incremento na sua qualidade e reprodutibilidade.

Objectives: To summarize the main points from the Brazilian's Ministry of Health Economic Evaluations (HEE) guideline. Methods: The guideline was developed through multiple rounds of iterative work, conducted by a multidisciplinary team of specialists in health economics, and where submitted to public consultation. Results: The decision problem should be defined through a structured research question. The study can be either primary data or model-based; in the first case, there is greater internal validity, while the second generates a superior generalizability. When the study is model-based and focused on a chronic disease, a Markov model can be usually employed, except for situations that points towards the need of a discrete event simulation (such as competition of individuals for scarce resources) or a dynamic transition model (for example, vaccination models and infectious diseases with high transmission rates between individuals). The preferred time horizon is the lifetime one, and the default discount rate is 5% for both costs and effectiveness. Costs should represent the Unified Health System (SUS) perspective and can be estimated through either gross-costing or micro-costing. Results should be presented as costs per quality adjusted life years (QALYs) whenever possible, to facilitate comparison with other studies. Sensitivity analyses should be widely employed, in order to evaluate the impact of uncertainty in the results produced by the model. Conclusions: It is expected that, with the standardization proposed in this guideline, the HEE production in Brazil has gains in quality and reproducibility.

Budgetary impact of diagnostic tests for visceral leishmaniasis in Brazil / Impacto orçamentário dos testes diagnósticos para leishmaniose visceral no Brasil / Impacto presupuestario de las pruebas diagnósticas para la leishmaniosis visceral en Brasil

Abstract: The aim of the present study was to estimate the financial costs of the incorporation and/or replacement of diagnostic tests for human visceral leishmaniasis (VL) in Brazil. The analysis was conducted from the perspective of the Brazilian Unified National Health System (SUS) over a period of three years. Six diagnostic tests were evaluated: the indirect immunofluorescence antibody test (IFAT), the IT LEISH rapid test, the parasitological examination of bone marrow aspirate, the direct agglutination test (DAT-LPC) standardized in the Clinical Research Laboratory, René Rachou Institute of the Oswaldo Cruz Foundation, the Kalazar Detect rapid test, and polymerase chain reaction (PCR). The assumptions used were the number of suspected cases of VL reported to the Brazilian Ministry of Health in 2014 and the direct cost of diagnostic tests. The costs to diagnose suspected cases of VL over three years using the IFAT and the DAT-LPC were estimated at USD 280,979.91 and USD 121,371.48, respectively. The analysis indicated that compared with the use of the IFAT, the incorporation of the DAT-LPC into the SUS would result in savings of USD 159,608.43. With regard to the budgetary impact of rapid tests, the use of IT LEISH resulted in savings of USD 21.708,72 over three years. Compared with a parasitological examination, diagnosis using PCR resulted in savings of USD 3,125,068.92 over three years. In this study, the replacement of the IFAT with the DAT-LPC proved financially advantageous. In addition, the replacement of the Kalazar Detect rapid test with the IT LEISH in 2015 was economically valuable, and the replacement of parasitological examination with PCR was indicated.

Resumo: O estudo teve como objetivo estimar os custos financeiros da incorporação e/ou substituição dos testes diagnósticos para a leishmaniose visceral (LV) humana no Brasil. A análise foi realizada na perspectiva do Sistema Único de Saúde (SUS) ao longo de três anos. Foram avaliados seis testes diagnósticos: reação de imunofluorescência indireta (RIFI), teste rápido IT LEISH, exame parasitológico de aspirado de medula óssea, teste de aglutinação direta DAT-LPC padronizado pelo Laboratório de Pesquisas Clínicas do Instituto René Rachou, Fundação Oswaldo Cruz, teste rápido Kalazar Detect e reação em cadeia da polimerase (PCR). Os parâmetros utilizados foram o número de casos suspeitos de LV notificados ao Ministério da Saúde em 2014 e o custo direto dos testes diagnósticos. Os custos do diagnóstico de casos suspeitos de LV ao longo de três anos usando o RIFI e DAT-LPC foram estimados em USD 280.979,91 e USD 121.371,48, respectivamente. De acordo com a análise, comparado ao uso do RIFI, a incorporação do DAT-LPC pelo SUS resultaria numa economia de USD 159.608,43. Com relação ao impacto dos testes rápidos, o uso do IT LEISH resultou em economia de USD 21.708,72 ao longo de três anos. Comparado ao exame parasitológico, o diagnóstico com PCR resultou em economia de USD 3.125.068,92 ao longo de três anos. Neste estudo, a substituição do RIFI pelo DAT-LPC mostrou ser financeiramente vantajosa. Além disso, a substituição do teste rápido Kalazar Detect com o IT LEISH em 2015 foi economicamente apropriada, e a substituição do exame parasitológico pela PCR está economicamente indicada.

Resumen: El objetivo del estudio fue estimar los costes financieros de la incorporación y/o sustitución de las pruebas diagnósticas para la leishmaniasis visceral (LV) humana en Brasil. El análisis se realizó desde la perspectiva del Sistema Único de Salud (SUS) a lo largo de tres años. Se evaluaron seis pruebas diagnósticas: reacción de inmunofluorescencia indirecta (RIFI), test rápido IT LEISH, examen parasitológico de aspirado de medula ósea, test de aglutinación directa DAT-LPC, estandarizado por el Laboratorio de Investigación Clínica del Centro de Investigación René Rachou, Fundación Oswaldo Cruz, test rápido Kalazar Detect y la reacción en cadena de la polimerasa (PCR). Los parámetros utilizados fueron el número de casos sospechosos de LV notificados al Ministerio de Salud en 2014 y el coste directo de los test diagnósticos. Los costes del diagnóstico de casos sospechosos de LV a lo largo de tres años, usando el RIFI y DAT-LPC, se estimaron en USD 280.979,91 y USD 121.371,48, respectivamente. De acuerdo con el análisis, comparado con el uso del RIFI, la incorporación del DAT-LPC por el SUS resultaría en un ahorro de USD 159.608,43. En relación con el impacto de los test rápidos, el uso del IT LEISH aportaba un ahorro de USD 21.708,72 a lo largo de tres años. Comparado con el examen parasitológico, el diagnóstico con PCR suponía un ahorro de USD 3.125.068,92 a lo largo de tres años. De acuerdo con el estudio, la sustitución del RIFI con el DAT-LPC mostró ser financieramente ventajosa. Asimismo, la sustitución del test rápido Kalazar Detect con el IT LEISH en 2015 representó un ahorro económico, y los resultados favorecieron la sustitución del examen parasitológico con PCR.

Cost-effectiveness analysis of diagnostic tests for human visceral leishmaniasis in Brazil.

BACKGROUND: The objective of study was to estimate the incremental cost-effectiveness ratio (ICER) of diagnostic options for visceral leishmaniasis (VL) in Brazil. METHODS: Six diagnostic tests were considered: IT LEISH, Kalazar Detect, DAT-LPC (DAT made in the Laboratório de Pesquisas Clínicas), IFAT, PCR and direct examination of bone marrow aspirate performed in either an ambulatory or a hospital setting. A database was built using the cost and effectiveness. The perspective of this study was the Brazilian public healthcare system and the results were expressed in costs per correctly diagnosed cases. RESULTS: In a favorable hypothetical scenario, DAT-LPC presented the lowest cost (US$4.92) and highest effectiveness (99%). Paired analyses showed that IT LEISH was dominant compared to IFAT, microscopy and Kalazar Detect and that Kalazar Detect was dominant over IFAT and microscopy. PCR was dominant over the bone marrow aspirate in the hospital and showed an ICER of 57.76 compared with aspirate in an ambulatory setting. CONCLUSIONS: These results highlight the need for the revision of algorithm for VL diagnostic in Brazil. Replacements of IFAT with DAT-LPC, Kalazar Detect with IT LEISH and bone marrow aspirate performed in a hospital setting with PCR are cost-effective public health measures.

Systematic Review of Economic Evaluations of Units Dedicated to Acute Coronary Syndromes.

BACKGROUND: Dedicated units for the care of acute coronary syndrome (ACS) have been submitted to economic evaluations; however, the results have not been systematically presented. OBJECTIVE: To identify and summarize economic outcomes of studies on hospital units dedicated to the initial care of patients with suspected or confirmed ACS. METHODS: A systematic review of literature to identify economic evaluations of chest pain unit (CPU), coronary care unit (CCU), or equivalent units was done. Two search strategies were used: the first one to identify economic evaluations irrespective of study design, and the second one to identify randomized clinical trials that reported economic outcomes. The following databases were searched: MEDLINE, EMBASE, CENTRAL, and National Health Service (NHS)Economic Evaluation Database. Data extraction was performed by two independent reviewers. Costs were inflated to 2012 values. RESULTS: Search strategies retrieved five partial economic evaluations based on observational studies, six randomized clinical trials that reported economic outcomes, and five model-based economic evaluations. Overall, cost estimates based on observational studies and randomized clinical trials reported statistically significant cost savings of more than 50% with the adoption of CPU care instead of routine hospitalization or CCU care for suspected low-to-intermediate risk patients with ACS (median per-patient cost US $1,969.89; range US $1,002.12-13,799.15). Model-based economic evaluations reported incremental cost-effectiveness ratios below US $ 50,000/quality-adjusted life-year for all comparisons between intermediate care unit, CPU, or CCU with routine hospital admissions. This finding was sensible to myocardial infarction probability. CONCLUSIONS: Published economic evaluations indicate that more intensive care is likely to be cost-effective in comparison to routine hospital admission for patients with suspected ACS.