Toward the Implementation of a Value Framework for Diagnostic Technologies: Operationalization, Piloting, and Validation in Latin America.

OBJECTIVES: In 2020, a group of 30 stakeholders from Latin America established 15 criteria for a diagnostic technologies value framework (D-VF) to help assess and inform decisions on diagnostic technologies. This article aims to present the operationalization, piloting, and initial validation of the framework for its implementation. METHODS: This work was carried out collaboratively with a variety of stakeholders. Three sequential phases were undertaken: (1) operationalization of the D-VF through a literature search for conceptual definitions and assessment tools, (2) piloting of the D-VF through a rapid health technology assessment document applying the methodology of the framework, and (3) a face validation process conducted through a virtual workshop, where usefulness and implementation aspects of the framework were assessed. RESULTS: The operationalization of the framework was conducted, and a methodological user guide was published. The D-VF criteria were applied in a health technology assessment document on human papilloma virus testing in cervical cancer screening. Also, an open-access training program was developed. Stakeholders agreed on the usefulness of the D-VF for assessment and decision-making stages of diagnostic technologies. However, they highlighted the need to improve technical capacities and the potential for added complexity when applying a D-VF with many criteria. The absence of an established value framework for diagnostic technologies in Latin America and the potential for strengthening technical capacities made the project valuable to those involved. CONCLUSIONS: The diagnostic technologies value framework was shown to be fit for implementation in real-life decision-making settings after the operationalization, piloting, and initial validation phases. Further experiences are important to support its implementation.

A Systematic Review of Value Criteria for Next-Generation Sequencing/Comprehensive Genomic Profiling to Inform Value Framework Development.

OBJECTIVES: To comprehensively identify and map an exhaustive list of value criteria for the assessment of next-generation sequencing/comprehensive genomic profiling (NGS/CGP), to be used as an aid in decision making. METHODS: We conducted a systematic review to identify existing value frameworks (VFs) applicable to any type of healthcare technology. VFs and criteria were mapped to a previously published Latin American (LA) VF to harmonize definitions and identify additional criteria and or subcriteria. Based on this analysis, we extracted a comprehensive, evidence-based list of criteria and subcriteria to be considered in the design of a NGS/CGP VF. RESULTS: A total of 42 additional VFs were compared with the LA VF, 88% were developed in high-income countries, 30% targeted genomic testing, and 16% specifically targeted oncology. A total of 242 criteria and subcriteria were extracted; 227 (94%) were fully/partially included in the LA VF; and 15 (6%) were new. Clinical benefit and economic aspects were the most common criteria. VFs oriented to genomic testing showed significant overlap with other VFs. Considering all criteria and subcriteria, a total of 18 criteria and 36 individual subcriteria were identified. CONCLUSIONS: Our study provides an evidence-based set of criteria and subcriteria for healthcare decision making useful for NGS/CGP as well as other health technologies. The resulting list can be beneficial to inform decision making and will serve as a foundation to co-create a multistakeholder NGS/CGP VF that is aligned with the needs and values of health systems and could help to improve patient access to high-value technologies.

Estimating the Effectiveness of Health Warnings on Cigarette Packaging in Nigeria: A Modeling Study.

INTRODUCTION: Tobacco consumption is associated with nearly 30 000 deaths annually in Nigeria alongside other adverse health and economic effects. Our objective was to estimate the health and economic implications of the current cigarette labeling policies (text-only HWs); new health warnings policies in the country (adding graphic health warnings with up to 60% coverage), and plain packaging policy as recommended by the World Health Organization. AIMS AND METHODS: We used a probabilistic state-transition individual microsimulation model, considering natural history, healthcare costs, and quality-of-life losses associated with main tobacco-attributable diseases; and the potential effects of packaging and labeling policies. We used three scenarios: (1) text-only health warnings (HWs) covering 50% of the pack, (2) introduction of graphic HWs of 50% (and later increasing to 80%) of the pack, and (3) plain packaging with HWs covering 80% of the pack. RESULTS: A total of 748 deaths are averted in the current situation; 7478 and 14 208 deaths can be averted with the new policy and with plain packaging, respectively. The number of cardiac, cerebrovascular, and cancer events that could be averted by adopting text and graphic HWs are 3093, 5093, and 1346, respectively; increasing to 5876, 9676, and 2557, respectively, with plain packaging. Up to 251 794 years were lost because of early deaths and disability, and ₦144.6 billion (USD 469 million) in health costs could be saved with HWs covering 50% to 80% of the pack over 10 years. With plain packaging and graphic HWs covering 80% of the package 478,408 years and ₦274.7 billion (USD 895 million) would be saved. CONCLUSIONS: The new cigarette labeling policy in Nigeria may yield significant health and economic benefits over 10 years. Moving the current policy to plain packaging can significantly improve these benefits. IMPLICATIONS: The new cigarette labeling policy that Nigeria is implementing should aim to achieve 100% compliance with its current regulation and the logical next step: Plain packaging with large warnings. The present study adds evidence of the potential health effects and cost savings of these levels of implementation, which is valuable for local policymakers.

The health, economic and social burden of smoking in Argentina, and the impact of increasing tobacco taxes in a context of illicit trade.

Tobacco tax increases, the most cost-effective measure in reducing consumption, remain underutilized in low and middle-income countries. This study estimates the health and economic burden of smoking in Argentina and forecasts the benefits of tobacco tax hikes, accounting for the potential effects of illicit trade. Using a probabilistic Markov microsimulation model, this study quantifies smoking-related deaths, health events, and societal costs. The model also estimates the health and economic benefits of different increases in the price of cigarettes through taxes. Annually, smoking causes 45,000 deaths and 221,000 health events in Argentina, costing USD 2782 million in direct medical expenses, USD 1470 million in labor productivity loss costs, and USD 1069 million in informal care costs-totaling 1.2% of the national gross domestic product. Even in a scenario that considers illicit trade of tobacco products, a 50% cigarette price increase through taxes could yield USD 8292 million in total economic benefits accumulated over a decade. Consequently, raising tobacco taxes could significantly reduce the health and economic burdens of smoking in Argentina while increasing fiscal revenue.

Health, economic and social burden of tobacco in Latin America and the expected gains of fully implementing taxes, plain packaging, advertising bans and smoke-free environments control measures: a modelling study.

OBJECTIVE: To investigate the tobacco-attributable burden on disease, medical costs, productivity losses and informal caregiving; and to estimate the health and economic gains that can be achieved if the main tobacco control measures (raising taxes on tobacco, plain packaging, advertising bans and smoke-free environments) are fully implemented in eight countries that encompass 80% of the Latin American population. DESIGN: Markov probabilistic microsimulation economic model of the natural history, costs and quality of life associated with the main tobacco-related diseases. Model inputs and data on labour productivity, informal caregivers' burden and interventions' effectiveness were obtained through literature review, surveys, civil registrations, vital statistics and hospital databases. Epidemiological and economic data from January to October 2020 were used to populate the model. FINDINGS: In these eight countries, smoking is responsible each year for 351 000 deaths, 2.25 million disease events, 12.2 million healthy years of life lost, US$22.8 billion in direct medical costs, US$16.2 billion in lost productivity and US$10.8 billion in caregiver costs. These economic losses represent 1.4% of countries' aggregated gross domestic products. The full implementation and enforcement of the four strategies: taxes, plain packaging, advertising bans and smoke-free environments would avert 271 000, 78 000, 71 000 and 39 000 deaths, respectively, in the next 10 years, and result in US$63.8, US$12.3, US$11.4 and US$5.7 billions in economic gains, respectively, on top of the benefits being achieved today by the current level of implementation of these measures. CONCLUSIONS: Smoking represents a substantial burden in Latin America. The full implementation of tobacco control measures could successfully avert deaths and disability, reduce healthcare spending and caregiver and productivity losses, likely resulting in large net economic benefits.

Making visible the cost of informal caregivers' time in Latin America: a case study for major cardiovascular, cancer and respiratory diseases in eight countries.

BACKGROUND: Informal care is a key element of health care and well-being for society, yet it is scarcely visible and rarely studied in health economic evaluations. This study aims to estimate the time use and cost associated with informal care for cardiovascular diseases, pneumonia and ten different cancers in eight Latin American countries (Argentina, Brazil, Chile, Colombia, Costa Rica, Ecuador, Mexico and Peru). METHODS: We carried out an exhaustive literature review on informal caregivers' time use, focusing on the selected diseases. We developed a survey for professional caregivers and conducted expert interviews to validate this data in the local context. We used an indirect estimate through the interpolation of the available data, for those cases in which we do not found reliable information. We used the proxy good method to estimate the monetary value of the use of time of informal care. National household surveys databases were processed to obtain the average wage per hour of a proxy of informal caregiver. Estimates were expressed in 2020 US dollars. RESULTS: The study estimated approximately 1,900 million hours of informal care annually and $ 4,300 million per year in average informal care time cost for these fifteen diseases and eight countries analyzed. Cardiovascular diseases accounted for an informal care burden that ranged from 374 to 555 h per year, while cancers varied from 512 to 1,825 h per year. The informal care time cost share on GDP varied from 0.26% (Mexico) to 1.38% (Brazil), with an average of 0.82% in the studied American countries. Informal care time cost represents between 16 and 44% of the total economic cost (direct medical and informal care cost) associated with health conditions. CONCLUSIONS: The study shows that there is a significant informal care economic burden -frequently overlooked- in different chronic and acute diseases in Latin American countries; and highlights the relevance of including the economic value of informal care in economic evaluations of healthcare.

[Burden of disease and economic burden attributable to the consumption of sugar-sweetened beverages in El SalvadorCarga de morbidade e econômica atribuível ao consumo de bebidas açucaradas em El Salvador]. / Carga de enfermedad y económica atribuible al consumo de bebidas azucaradas en El Salvador.

Objective: To estimate the burden of disease and economic burden attributable to the consumption of sugar-sweetened beverages in El Salvador. Methods: A comparative risk model was used to estimate the effects on deaths, health events, disability-adjusted life years (DALYs), and direct medical costs attributable to the consumption of sugar-sweetened beverages. Results: A total of 520 deaths (8 per 100 000 individuals), 214 082 health events (3 220 per 100 000 individuals) and 16 643 DALYs could be attributable to the consumption of sugar-sweetened beverages in El Salvador, representing US$69.35 million in direct medical costs for the year 2020. In particular, type 2 diabetes (T2DM) events attributable to the consumption of sugar-sweetened beverages could represent more than 20% of total T2DM cases in the country. Conclusion: A high number of deaths, events, and costs could be attributed to the consumption of sugar-sweetened beverages in El Salvador.

Objetivo: Estimar a carga de morbidade e econômica atribuível ao consumo de bebidas açucaradas em El Salvador. Métodos: Foi utilizado um modelo de risco comparativo para estimar os efeitos sobre óbitos, eventos de saúde, anos perdidos devido a morte prematura ou vividos com incapacidade (AVAI) e custos médicos diretos atribuíveis ao consumo de bebidas açucaradas. Resultados: Um total de 520 mortes (8 por 100 00 indivíduos), 214 082 eventos de saúde (3 220 por 100 000 indivíduos) e 16 643 AVAI podem ser atribuídos ao consumo de bebidas açucaradas em El Salvador, o que representa US$ 69,35 milhões em custos médicos diretos para o ano de 2020. Os eventos de diabetes mellitus tipo 2 (DM2) atribuíveis ao consumo de bebidas açucaradas, em especial, podem representar mais de 20% do total de casos de DM2 no país. Conclusões: Um número elevado de mortes, eventos de saúde e custos pode ser atribuído ao consumo de bebidas açucaradas em El Salvador.

The health and economic burden associated with sugar-sweetened beverage consumption in Trinidad and Tobago.

BACKGROUND: In Trinidad and Tobago, non-communicable diseases (NCDs) are the leading cause of death. Unhealthy diet is one modifiable NCD risk factor, which contributes to the NCD burden. The consumption of sugar-sweetened beverages (SSBs) has been associated with an increased risk of NCDs. AIM: The aim of this paper is to estimate the burden of disease and economic costs associated with the consumption of SSBs in Trinidad and Tobago as evidence to support the implementation of health and fiscal policies on SSB consumption. METHODS: The results of this study were obtained through the use of a mathematical model which used a comparative risk assessment approach to estimate the health and economic burden associated with SSB intake, by sex and age. RESULTS: Estimates for one year showed that SSB consumption was associated with approximately 15,000 cases of overweight and obesity in adults and 11,700 cases in children, 28% of all the cases of diabetes and overall, an estimated 387 deaths and 9000 years of healthy life were lost due to premature death and disability. Approximately US$23.1 million was spent in the public healthcare system to treat diseases associated with consumption of sugary beverages. CONCLUSIONS: The consumption of SSBs is associated with increases in diseases, deaths and rising healthcare costs in Trinidad and Tobago. It is hoped that the results of this study will provide an added rationale and impetus for the implementation of policies to reduce the consumption of SSBs.

Evidence-Informed Update of Argentina's Health Benefit Package: Application of a Rapid Review Methodology.

OBJECTIVES: Argentina has a fragmented healthcare system with social security covering almost two thirds of the population. Its benefit package-called compulsory medical program (PMO; by its Spanish acronym Programa Médico Obligatorio)-has not been formally and widely updated since 2005. However, laws, clinical practice guidelines (CPGs), and a high-cost technology reimbursement fund complement it. Our objective was to comprehensively review such a PMO and propose an update considering the corresponding complementary sources. METHODS: We followed four steps: (i) identification of health technologies from the current PMO and complementary sources, (ii) prioritization, (iii) assessment through rapid health technology assessment (HTA), and (iv) appraisal and recommendations. We evaluated three value domains: quality of evidence, net benefit, and economics, which were summarized in a five-category recommendation traffic-light scale ranging from a strong recommendation in favor of inclusion to a strong recommendation for exclusion. RESULTS: Eight hundred fifty technologies were identified; 164 of those, considered as high priority, were assessed through rapid HTAs. Those technologies mentioned in laws and CPGs were mostly outpatient essential medicines, whereas those from the reimbursement system were mostly high-cost drugs; of these 101 technologies, 50 percent were recommended to be kept in the PMO. The other 63 (identified by the Superintendence of Health Services, technology producers, and patients) were mostly medical procedures and high-cost drugs; only 25 percent of those resulted in a favorable recommendation. CONCLUSIONS: A methodology based on four clearly identified steps was used to carry out a comprehensive review of an outdated and fragmented benefit package. The use of rapid HTAs and a traffic-light recommendation framework facilitated the deliberative evidence-based update.

Deliberative processes in decision making informed by health technology assessment in Latin America.

OBJECTIVE: The objective of Health Technology Assessment International's 6th Latin America Policy Form, held in 2021, was to explore the implementation of deliberative processes in the framework of health technology assessment (HTA) and how agencies in the region could involve stakeholders in this process. METHODS: This paper is based on a preparatory survey, a background document, and the deliberative work of participants at the virtual Forum conducted in 2021. There were ninety-one participants in the open session and fifty-two in the closed sessions, representing twelve countries and diverse areas of the health sector. RESULTS: While there are mechanisms in most countries in Latin America to consider stakeholder involvement to some degree, it remains reduced or limited to a consultative role, making true participative involvement rare. There are significant barriers and structural and contextual limitations that have impeded or slowed progress toward deliberative processes. Relatively low levels of institutionalization and knowledge about HTA, as well as the lack of trust among stakeholders are important challenges. This situation has impacted health systems by diminishing the legitimacy of decisions and the very structures and processes of HTA. CONCLUSION: The Forum's broad group of participants identified barriers, facilitators, and recommendations to improve the use of deliberative processes in Latin America to foster improved fairness and reasonableness in HTA and decision making.

A Value Framework for the Assessment of Diagnostic Technologies: A Proposal Based on a Targeted Systematic Review and a Multistakeholder Deliberative Process in Latin America.

OBJECTIVES: there are very few value frameworks (VFs) to assess health technologies that are focused on diagnostic tests; they usually do not reflect a multistakeholder process; and they are all developed in high-income countries. Our project performed a targeted systematic review, with the objective of proposing an evidence-based, up-to-date VF informed by a multinational multistakeholder group working in the health technology assessment (HTA) space. METHODS: (1) A targeted systematic review, with the aim to identify existing VFs and their dimensions; and (2) generation a VF proposal through a mixed-methods, qualitative-quantitative approach. RESULTS: From 73 citations identified, 20 met our inclusion criteria and served to provide the initial list of dimensions for our VF. An initial list of criteria and subcriteria for a preliminary VF was proposed. After a full-day deliberative face-to-face meeting with 30 relevant stakeholders from seven Latin American countries and the United Kingdom, the final VF was defined, consisting of 15 criteria: five "essential or core," six highly relevant, three moderately relevant, and one of low relevance. Barriers and facilitators of value assessment of diagnostic technologies were also discussed. CONCLUSIONS: We propose a VF oriented to diagnostic technologies based on a targeted systematic review and a participatory process with key HTA stakeholders. It is the first to be produced in a lower and middle income setting but can also be potentially useful in other contexts aimed to assist decision-making processes with these particularly complex health technologies.

Improving the monitoring of chronic heart failure in Argentina: is the implantable pulmonary artery pressure with CardioMEMS Heart Failure System cost-effective?

BACKGROUND: The CardioMEMS® sensor is a wireless pulmonary artery pressure device used for monitoring symptomatic heart failure (HF). The use of CardioMEMS was associated with a reduction of hospitalizations of HF patients, but the acquisition cost could be high in low-and-middle income countries. Evidence of cost-effectiveness is needed to help decision-makers to allocate resources according to "value for money". This study is aimed at estimating the cost-effectiveness of CardioMEMS used in HF patients from the third-party payer perspective -Social Security (SS) and Private Sector (PS)- in Argentina. METHODS: A Markov model was developed to estimate the cost-effectiveness of CardioMEMS versus usual medical care over a lifetime horizon. The model was applied to a hypothetical population of patients with HF functional class III with at least one hospitalization in the previous 12 months. The main outcome was the incremental cost-effectiveness ratio (ICER). To populate the model we retrieved clinical, epidemiological and utility parameters from the literature, whilst direct medical costs were estimated through a micro-costing approach (exchange rate USD 1 = ARS 76.95). Uncertainties in all parameters were assessed by deterministic, probabilistic and scenario sensitivity analysis. RESULTS: Compared with the usual medical care, CardioMEMS increased quality-adjusted life years (QALY) by 0.37 and increased costs per patient by ARS 1,081,703 for SS and ARS 919,051 for PS. The resultant ICER was ARS 2,937,756 per QALY and ARS 2,496,015 per QALY for SS and PS, respectively. ICER was most sensitive to the hazard ratio of HF hospital admission and the acquisition price of CardioMEMS. The probability that CardioMEMS is cost-effective at one (ARS 700,473), three (ARS 2,101,419,) and five (ARS 3,502,363) Gross Domestic Product per capita is 0.6, 17.9 and 64.1% for SS and 5.4, 33.3 and 73.2% for PS. CONCLUSIONS: CardioMEMS was more effective and more costly than usual care in class III HF patients. Since in Argentina there is no current explicit threshold, the final decision to determine its cost-effectiveness will depend on the willingness-to-pay for QALYs in each health subsector.

Sugar sweetened beverages attributable disease burden and the potential impact of policy interventions: a systematic review of epidemiological and decision models.

BACKGROUND: Around 184,000 deaths per year could be attributable to sugar-sweetened beverages (SSBs) consumption worldwide. Epidemiological and decision models are important tools to estimate disease burden. The purpose of this study was to identify models to assess the burden of diseases attributable to SSBs consumption or the potential impact of health interventions. METHODS: We carried out a systematic review and literature search up to August 2018. Pairs of reviewers independently selected, extracted, and assessed the quality of the included studies through an exhaustive description of each model's features. Discrepancies were solved by consensus. The inclusion criteria were epidemiological or decision models evaluating SSBs health interventions or policies, and descriptive SSBs studies of decision models. Studies published before 2003, cost of illness studies and economic evaluations based on individual patient data were excluded. RESULTS: We identified a total of 2766 references. Out of the 40 included studies, 45% were models specifically developed to address SSBs, 82.5% were conducted in high-income countries and 57.5% considered a health system perspective. The most common model's outcomes were obesity/overweight (82.5%), diabetes (72.5%), cardiovascular disease (60%), mortality (52.5%), direct medical costs (57.35%), and healthy years -DALYs/QALYs- (40%) attributable to SSBs. 67.5% of the studies modelled the effect of SSBs on the outcomes either entirely through BMI or through BMI plus diabetes independently. Models were usually populated with inputs from national surveys -such us obesity prevalence, SSBs consumption-; and vital statistics (67.5%). Only 55% reported results by gender and 40% included children; 30% presented results by income level, and 25% by selected vulnerable groups. Most of the models evaluated at least one policy intervention to reduce SSBs consumption (92.5%), taxes being the most frequent strategy (75%). CONCLUSIONS: There is a wide range of modelling approaches of different complexity and information requirements to evaluate the burden of disease attributable to SSBs. Most of them take into account the impact on obesity, diabetes and cardiovascular disease, mortality, and economic impact. Incorporating these tools to different countries could result in useful information for decision makers and the general population to promote a deeper implementation of policies to reduce SSBs consumption. PROSPERO PROTOCOL NUMBER: CRD42020121025 .

Identification and selection of health technologies for assessment by agencies in support of reimbursement decisions in Latin America.

OBJECTIVE: There is no health system that has the resources to evaluate all technologies. The presence of a clear process to prioritize health technologies for assessment by health technology assessment (HTA) agencies is a good practice principle recognized at the international level. The objective of Health Technology Assessment International's 2020 Latin American Policy Forum (LatamPF) was to explore how to improve the way HTA agencies in Latin America identify and prioritize technologies for assessment. METHODS: This paper is based on a background document, a survey, and the deliberations of the members of the LatamPF (forty-six participants from eleven countries) using a design thinking methodology. RESULTS: Participants agreed that a lack of clear prioritization mechanisms results in HTA processes and decisions that are perceived to be of low transparency and overly exposed to political or interest group pressures. The LatamPF identified barriers and recommended actions to improve HTA prioritization mechanisms in Latin America. The criteria identified as the most important to be taken into consideration by HTA agencies in the region when prioritizing a technology for assessment were: the burden of illness, the potential clinical benefit, the alignment with national health priorities, the potential impact on equity, a lack of treatment alternatives for patients, and the potential economic impact. CONCLUSIONS: Forum participants agreed that the establishment of transparent prioritization processes is a key element for all health systems. Improvements in these processes will strengthen HTA and provide greater legitimacy to decision making.

[Mecanismos de identificación y priorización de las tecnologías sanitarias a ser evaluadas por las Agencias de ETESA para decisiones de cobertura en Latino America].

OBJETIVO: Ningún sistema de salud cuenta con los recursos necesarios para evaluar todas las tecnologías. Contar con un proceso claro para priorizar qué tecnologías serán evaluadas por las agencias de evaluación de tecnologías sanitarias (ETESA) constituye un principio de buena práctica reconocido a nivel internacional. El objetivo del Foro de Políticas en Latino América (LatamPF) 2020 de Health Technology Assessment International fue explorar cómo puede mejorarse la forma en que las agencias de ETESA de Latino América identifican y priorizan las tecnologías a ser evaluadas. MÉTODOS: Este manuscrito está basado en un documento base, una encuesta, y en el trabajo deliberativo realizado por los miembros (cuarenta y seis participantes, once países) que participaron del LatamPF, a través de la metodología design-thinking. RESULTADOS: Los participantes coincidieron en que la falta de mecanismos claros de priorización trae como consecuencia una falta de legitimidad de las decisiones y procesos de ETESA, que son percibidos como poco transparentes y demasiado expuestos a presiones políticas o de grupos de interés. También se identificaron barreras y acciones para mejorar los mecanismos de priorización de ETESA en América Latina. Los criterios identificados como más importantes para ser tenidos en cuenta por las agencias de ETESA de la región al momento de priorizar una tecnología para ser evaluada fueron la carga de enfermedad, el potencial beneficio clínico, la alineación con prioridades de salud nacionales, el potencial impacto en la equidad, ausencia de otras alternativas para los pacientes, y el potencial impacto económico. CONCLUSIONES: Los participantes del Foro coincidieron en que el establecimiento de procesos transparentes de priorización es un elemento clave para todos los sistemas de salud. Las mejoras en este proceso fortalecerán la ETESA en Latino América y darán mayor legitimidad a sus decisiones.

The Influence of Hydrolytic Enzymes on Tannin Adsorption-Desorption onto Grape Cell Walls in a Wine-Like Matrix.

This study evaluates the capacity of four hydrolytic enzymes to limit the interactions between grape cell-walls and tannins and/or to favor tannin desorption. Adsorption and desorption tests were conducted by mixing a commercial seed tannin with purified skin cell-walls from Syrah grapes, in the presence or absence of hydrolytic enzymes, in a model-wine solution. The effects of the enzymes were evaluated by measuring the tannins in solution by High Performance Liquid Chromatography (HPLC) and the changes in the cell wall polysaccharide network by Comprehensive Microarray Polymer Profiling (COMPP) while the polysaccharides liberated from cell walls were analyzed by Size Exclusion Chromatography (SEC). The results showed that the enzymes limited the interaction between tannins and cell walls, especially cellulase, pectinase and xylanase, an effect associated with the cell wall structural modifications caused by the enzymes, which reduced their capacity to bind tannins. With regards to the tannin desorption process, enzymes did not play a significant role in liberating bound tannins. Those enzymes that showed the highest effect in limiting the adsorption of tannins and in disorganizing the cell wall structure, cellulase and pectinase, did not lead to a desorption of bound tannins, although they still showed a capacity of affecting cell wall structure. The results indicate that enzymes are not able to access those polysaccharides where tannins are bound, thus, they are not a useful tool for desorbing tannins from cell walls. The practical importance implications of these findings are discussed in the manuscript.

Health and Economic Impact of Health Warnings and Plain Tobacco Packaging in Seven Latin American Countries: Results of a Simulation Model.

INTRODUCTION: The burden of disease attributable to tobacco use in Latin America is very high. Our objective was to evaluate the 10-year potential impact of current legislation related to cigarette packaging and warnings and expected effects of moving to a higher level of strategies implementing cigarette plain packaging on health and cost outcomes in Argentina, Bolivia, Brazil, Chile, Colombia, Mexico, and Peru, using a microsimulation model. AIMS AND METHODS: We used a probabilistic state-transition microsimulation model, considering natural history, costs, and quality of life losses associated with main tobacco-related diseases. We followed up individuals in hypothetical cohorts and calculated health outcomes annually to obtain aggregated long-term population health outcomes and costs. We performed a literature review to estimate effects and analyzed studies and information from ministries, relevant organizations, and national surveys. We calibrated the model comparing the predicted disease-specific mortality rates with local statistics. RESULTS: Current graphic warnings already in place in each country could avert, during 10 years, 69 369 deaths and 638 295 disease events, adding 1.2 million years of healthy life and saving USD 5.3 billion in the seven countries. If these countries implemented plain packaging strategies, additional 155 857 premature deaths and 4 133 858 events could be averted, adding 4.1 million healthy years of life and saving USD 13.6 billion in direct health care expenses of diseases attributable to smoking. CONCLUSIONS: Latin American countries should not delay the implementation of this strategy that will alleviate part of the enormous health and financial burden that tobacco poses on their economies and health care systems. IMPLICATIONS: Tobacco smoking is the single most preventable and premature mortality cause in the world. The Framework Convention on Tobacco Control, supported by the World Health Organization, introduced a package of evidence-based measures for tobacco control. This study adds evidence on the potential health effects and savings of implementing cigarette plain packaging in countries representing almost 80% of the Latin American population; findings are valuable resources for policy makers in the region.

Interventions for the control of Aedes aegypti in Latin America and the Caribbean: systematic review and meta-analysis.

OBJECTIVE: To determine the effectiveness and degree of implementation of interventions for the control of Aedes aegypti in Latin America and the Caribbean (LAC) as reported in scientific literature. METHODS: We searched MEDLINE, EMBASE, CENTRAL, SOCINDEX, and LILACS, for experimental and observational studies, economic assessments and qualitative experiences carried out in LAC from 2000 to 2016. We assessed incidence and morbimortality of Aedes aegypti-related diseases and entomological indices: Breteau (containers), House, and Pupae per Person. We used GRADE methodology for assessing quality of evidence. RESULTS: Of 1826 records retrieved, 75 were included and 9 cluster randomised clinical trials could be meta-analysed. We did not identify any intervention supported by a high certainty of evidence. In consistency with qualitative evidence, health education and community engagement probably reduces the entomological indices, as do the use of insecticide-treated materials, indoor residual spraying and the management of containers. There is low certainty of evidence supporting the use of ovitraps or larvitraps, and the integrated epidemiological surveillance strategy to improve indices and reduce the incidence of dengue. The reported degree of implementation of these vector control interventions was variable and most did not extend to whole cities and were not sustained beyond 2 years. CONCLUSIONS: We found a general lack of evidence on effectiveness of vector control in the region, despite a few interventions that showed moderate to low certainty of evidence. It is important to engage and educate the community, apart from achieving the implementation of integrated actions between the health and other sectors at national and regional level.

OBJECTIF: Déterminer l'efficacité et le degré d'implémentation des interventions de lutte contre Aedes aegypti en Amérique latine et dans les Caraïbes (ALC), tels que décrits dans la littérature scientifique. MÉTHODES: Nous avons effectué des recherches dans MEDLINE, EMBASE, CENTRAL, SOCINDEX et LILACS pour des études expérimentales et d'observation, des évaluations économiques et des expériences qualitatives réalisées dans la région ALC de 2000 à 2016. Nous avons évalué l'incidence et la morbimortalité des maladies liées à Aedes aegypti et les indices entomologiques: Breteau (conteneurs), Maison et Pupe par Personne. Nous avons utilisé la méthodologie GRADE pour évaluer la qualité des données. RÉSULTATS: Sur 1.826 articles retrouvés, 75 ont été inclus et 9 essais cliniques randomisés en grappes ont pu être méta-analysés. Nous n'avons identifié aucune intervention étayée par une certitude élevée. De manière cohérente avec les preuves qualitatives, l'éducation pour la santé et la participation de la communauté réduisent probablement les indices entomologiques, de même que l'utilisation de matériaux traités à l'insecticide, la pulvérisation de résidus à l'intérieur et la gestion des conteneurs. Il existe peu de certitude quant aux données soutenant l'utilisation des ovitraps ou des larvitraps et de la stratégie de surveillance épidémiologique intégrée visant à améliorer les indices et à réduire l'incidence de la dengue. Le degré d'implémentation rapporté pour ces interventions de lutte antivectorielle était variable et la plupart ne s'étendaient pas à l'entièreté des villes et ne duraient pas plus de deux ans. CONCLUSIONS: Nous avons constaté un manque général de preuves sur l'efficacité de la lutte antivectorielle dans la région, malgré quelques interventions montrant une certitude modérée à faible. Il est important d'impliquer et d'éduquer la communauté, outre la mise en œuvre d'actions intégrées entre le secteur de la santé et d'autres secteurs aux niveaux national et régional.

Alcohol consumption's attributable disease burden and cost-effectiveness of targeted public health interventions: a systematic review of mathematical models.

BACKGROUND: Around 6% of total deaths are related to alcohol consumption worldwide. Mathematical models are important tools to estimate disease burden and to assess the cost-effectiveness of interventions to address this burden. METHODS: We carried out a systematic review on models, searching main health literature databases up to July 2017. Pairs of reviewers independently selected, extracted data and assessed the quality of the included studies. Discrepancies were resolved by consensus. We selected those models exploring: a) disease burden (main metrics being attributable deaths, disability-adjusted life years, quality-adjusted life years) or b) economic evaluations of health interventions or policies, based on models including the aforementioned outcomes. We grouped models into broad families according to their common central methodological approach. RESULTS: Out of 4295 reports identified, 63 met our inclusion criteria and were categorized in three main model families that were described in detail: 1) State transition -i.e Markov- models, 2) Life Table-based models and 3) Attributable fraction-based models. Most studies pertained to the latter one (n = 29, 48.3%). A few miscellaneous models could not be framed into these families. CONCLUSIONS: Our findings can be useful for future researchers and decision makers planning to undertake alcohol-related disease burden or cost-effectiveness studies. We found several different families of models. Countries interested in adopting relevant public health measures may choose or adapt the one deemed most convenient, based on the availability of existing data at the local level, burden of work, and public health and economic outcomes of interest.

Community-based cardiovascular health promotion in Argentina. A systematic review.

In Argentina, cardiovascular disease (CVD) accounts for 30% of deaths and more than 600 000 disability-adjusted life years. However, no reviews describing local studies on interventions to address CVD risk factors have been identified. The purpose of this study is to characterize those population-based interventions and public policies implemented in Argentina to reduce the burden of cardiovascular disease with an adequate evaluation of their impact on population health. We conducted a systematic review of studies that assessed interventions in health promotion and/or primary prevention conducted in adult populations of Argentina, addressing specific CVD factors, from 1999 to 2016. We searched major bibliographic databases, grey literature, ministries and secretariats of health, and academic national libraries. Key informants, non-governmental organizations, universities, hospitals and experts were also contacted. We applied specific inclusion criteria. We assessed the methodological quality of the studies and reported the effectiveness and impact of population interventions and policies, as well as process evaluations' characteristics. After removing duplicates we identified 1686 references from databases. After reviewing title and abstracts 18 studies were selected, five of them corresponded to evaluations of public policies-all addressing tobacco smoking. We presented a structured review of each experience. Most of the studies were deemed to entail moderate or high risk of bias. We summarized the findings and characteristics of these studies, including implementation strategies, process and impact evaluation. This is the first systematic review of interventions focused on primary prevention and health promotion to counter CVD and diabetes in Argentina.