Development and application of a dynamic transmission model of health systems' preparedness and response to COVID-19 in twenty-six Latin American and Caribbean countries

The global impact of COVID-19 has challenged health systems across the world. This situation highlighted the need to develop policies based on scientific evidence to prepare the health systems and mitigate the pandemic. In this scenario, governments were urged to predict the impact of the measures they were implementing, how they related to the population's behavior, and the capacity of health systems to respond to the pandemic. The overarching aim of this research was to develop a customizable and open-source tool to predict the impact of the expansion of COVID-19 on the level of preparedness of the health systems of different Latin American and the Caribbean countries, with two main objectives. Firstly, to estimate the transmission dynamics of COVID-19 and the preparedness and response capacity of health systems in those countries, based on different scenarios and public policies implemented to control, mitigate, or suppress the spread of the epidemic. Secondly, to facilitate policy makers' decisions by allowing the model to adjust its parameters according to the specific pandemic trajectory and policy context. How many infections and deaths are estimated per day?;When are the peaks of cases and deaths expected, according to the different scenarios?;Which occupancy rate will ICU services have along the epidemiological curve?;When is the optimal time increase restrictions in order to prevent saturation of ICU beds?, are some of the key questions that the model can respond, and is publicly accessible through the following link: http://shinyapps.iecs.org.ar/modelo-covid19/. This open-access and open code tool is based on a SEIR model (Susceptible, Exposed, Infected and Recovered). Using a deterministic epidemiological model, it allows to frame potential scenarios for long periods, providing valuable information on the dynamics of transmission and how it could impact on health systems through multiple customized configurations adapted to specific characteristics of each country.

Safety of COVID-19 vaccines during pregnancy: A systematic review and meta-analysis.

BACKGROUND: Assessment of COVID-19 vaccines safety during pregnancy is urgently needed. METHODS: We conducted a systematic review and meta-analysis to evaluate the safety of COVID-19 vaccines, including their components and technological platforms used in other vaccines during pregnancy and animal studies to complement direct evidence. We searched literature databases from its inception to September 2021 without language restriction, COVID-19 vaccine websites, and reference lists of other systematic reviews and the included studies. Pairs of reviewers independently selected, data extracted, and assessed the risk of bias of the studies. Discrepancies were resolved by consensus. (PROSPERO CRD42021234185). RESULTS: We retrieved 8,837 records from the literature search; 71 studies were included, involving 17,719,495 pregnant persons and 389 pregnant animals. Most studies (94%) were conducted in high-income countries, were cohort studies (51%), and 15% were classified as high risk of bias. We identified nine COVID-19 vaccine studies, seven involving 309,164 pregnant persons, mostly exposed to mRNA vaccines. Among non-COVID-19 vaccines, the most frequent exposures were AS03 and aluminum-based adjuvants. A meta-analysis of studies that adjusted for potential confounders showed no association with adverse outcomes, regardless of the vaccine or the trimester of vaccination. Neither the reported rates of adverse pregnancy outcomes nor reactogenicity exceeded expected background rates, which was the case for ASO3- or aluminum-adjuvanted non-COVID-19 vaccines in the proportion meta-analyses of uncontrolled studies/arms. The only exception was postpartum hemorrhage after COVID-19 vaccination (10.40%; 95% CI: 6.49-15.10%), reported by two studies; however, the comparison with non-exposed pregnant persons, available for one study, found non-statistically significant differences (adjusted OR 1.09; 95% CI 0.56-2.12). Animal studies showed consistent results with studies in pregnant persons. CONCLUSION: We found no safety concerns for currently administered COVID-19 vaccines during pregnancy. Additional experimental and real-world evidence could enhance vaccination coverage. Robust safety data for non-mRNA-based COVID-19 vaccines are still needed.

Safety, immunogenicity, and effectiveness of COVID-19 vaccines for pregnant persons: A protocol for systematic review and meta analysis.

INTRODUCTION: Numerous vaccines have been evaluated and approved for coronavirus disease 2019 (COVID-19). Since pregnant persons have been excluded from most clinical trials of COVID-19 vaccines, sufficient data regarding the safety of these vaccines for the pregnant person and their fetus have rarely been available at the time of product licensure. However, as COVID-19 vaccines have been deployed, data on the safety, reactogenicity, immunogenicity, and efficacy of COVID-19 vaccines for pregnant persons and neonates are becoming increasingly available. A living systematic review and meta-analysis of the safety and effectiveness of COVID-19 vaccines for pregnant persons and newborns could provide the information necessary to help guide vaccine policy decisions. METHODS AND ANALYSIS: We aim to conduct a living systematic review and meta-analysis based on biweekly searches of medical databases (e.g., MEDLINE, EMBASE, CENTRAL) and clinical trial registries to systematically identify relevant studies of COVID-19 vaccines for pregnant persons. Pairs of reviewers will independently select, extract data, and conduct risk of bias assessments. We will include randomized clinical trials, quasi-experimental studies, cohort, case-control, cross-sectional studies, and case reports. Primary outcomes will be the safety, efficacy, and effectiveness of COVID-19 vaccines in pregnant persons, including neonatal outcomes. Secondary outcomes will be immunogenicity and reactogenicity. We will conduct paired meta-analyses, including prespecified subgroup and sensitivity analyses. We will use the grading of recommendations assessment, development, and evaluation approach to evaluate the certainty of evidence.

Cost-effectiveness of COVID-19 vaccination in Latin America and the Caribbean: an analysis in Argentina, Brazil, Chile, Colombia, Costa Rica, Mexico, and Peru. (preprint)

Objective. Our study analyzes the cost-effectiveness of the COVID-19 vaccination campaign in Argentina, Brazil, Chile, Colombia, Costa Rica, Mexico, and Peru.  Methods. Using a previously published SVEIR model, we analyzed the impact of a vaccination campaign (2021) from a national healthcare perspective. The primary outcomes were quality adjusted life years (QALYs) lost and total costs. Other outcomes included COVID-19 cases, hospitalizations, deaths, and life years. We applied a discount rate of 3% for health outcomes. We modeled a realistic vaccination campaign in each country (the country-specific campaign implemented). Additionally, we assessed a standard campaign (similar, “typical“ for all countries), and an optimized campaign (similar in all countries with higher but plausible population coverage). One-way deterministic sensitivity analyses were performed.  Findings. Vaccination was health improving as well as cost-saving in almost all countries and scenarios. Our analysis shows that vaccination in this group of countries prevented 573,141 deaths (508,826 standard; 685,442 optimized) and gained 5.07 million QALYs (4.53 standard; 6.03 optimized). Despite the incremental costs of vaccination campaigns, they had a total net cost saving to the health system of US$16.29 billion (US$16.47 standard; US$18.58 optimized). The realistic vaccination campaign in Chile was the only scenario, which was not cost saving, but it was still highly cost-effective with an ICER of US$22 per QALY gained. Main findings were robust in the sensitivity analyses.  Interpretation. The COVID-19 vaccination campaign in seven Latin American and Caribbean countries -that comprise nearly 80% of the region- was beneficial for population health and was also cost-saving or highly cost-effective.

Multisystem Inflammatory Syndrome Temporally Related to COVID-19 in Children From Latin America and the Caribbean Region: A Systematic Review With a Meta-Analysis of Data From Regional Surveillance Systems.

Background: With the emergence of the COVID-19 pandemic, increasing numbers of cases of the multisystem inflammatory syndrome in children (MIS-C) have been reported worldwide; however, it is unclear whether this syndrome has a differential pattern in children from Latin America and the Caribbean (LAC). We conducted a systematic review and meta-analysis to analyze the epidemiological, clinical, and outcome characteristics of patients with MIS-C in LAC countries. Methods: A systematic literature search was conducted in the main electronic databases and scientific meetings from March 1, 2020, to June 30, 2021. Available reports on epidemiological surveillance of countries in the region during the same period were analyzed. Results: Of the 464 relevant studies identified, 23 were included with 592 patients with MIS-C from LAC. Mean age was 6.6 years (IQR, 6-7.4 years); 60% were male. The most common clinical manifestations were fever, rash, and conjunctival injection; 59% showed Kawasaki disease. Pool proportion of shock was 52%. A total of 47% of patients were admitted to the pediatric intensive care unit (PICU), 23% required mechanical ventilation, and 74% required vasoactive drugs. Intravenous gamma globulin alone was administered in 87% of patients, and in combination with steroids in 60% of cases. Length of hospital stay was 10 days (IQR, 9-10) and PICU stay 5.75 (IQR, 5-6). Overall case fatality ratio was 4% and for those hospitalized in the PICU it was 7%. Conclusion: Limited information was available on the clinical outcomes. Improvements in the surveillance system are required to obtain a better epidemiologic overview in the region.

Development and application of a dynamic transmission model of health systems' preparedness and response to COVID-19 in twenty-six Latin American and Caribbean countries.

The global impact of COVID-19 has challenged health systems across the world. This situation highlighted the need to develop policies based on scientific evidence to prepare the health systems and mitigate the pandemic. In this scenario, governments were urged to predict the impact of the measures they were implementing, how they related to the population's behavior, and the capacity of health systems to respond to the pandemic. The overarching aim of this research was to develop a customizable and open-source tool to predict the impact of the expansion of COVID-19 on the level of preparedness of the health systems of different Latin American and the Caribbean countries, with two main objectives. Firstly, to estimate the transmission dynamics of COVID-19 and the preparedness and response capacity of health systems in those countries, based on different scenarios and public policies implemented to control, mitigate, or suppress the spread of the epidemic. Secondly, to facilitate policy makers' decisions by allowing the model to adjust its parameters according to the specific pandemic trajectory and policy context. How many infections and deaths are estimated per day?; When are the peaks of cases and deaths expected, according to the different scenarios?; Which occupancy rate will ICU services have along the epidemiological curve?; When is the optimal time increase restrictions in order to prevent saturation of ICU beds?, are some of the key questions that the model can respond, and is publicly accessible through the following link: http://shinyapps.iecs.org.ar/modelo-covid19/. This open-access and open code tool is based on a SEIR model (Susceptible, Exposed, Infected and Recovered). Using a deterministic epidemiological model, it allows to frame potential scenarios for long periods, providing valuable information on the dynamics of transmission and how it could impact on health systems through multiple customized configurations adapted to specific characteristics of each country.

Multisystem Inflammatory Syndrome Temporally Related to COVID-19 in Children From Latin America and the Caribbean Region: A Systematic Review With a Meta-Analysis of Data From Regional Surveillance Systems

Background With the emergence of the COVID-19 pandemic, increasing numbers of cases of the multisystem inflammatory syndrome in children (MIS-C) have been reported worldwide;however, it is unclear whether this syndrome has a differential pattern in children from Latin America and the Caribbean (LAC). We conducted a systematic review and meta-analysis to analyze the epidemiological, clinical, and outcome characteristics of patients with MIS-C in LAC countries. Methods A systematic literature search was conducted in the main electronic databases and scientific meetings from March 1, 2020, to June 30, 2021. Available reports on epidemiological surveillance of countries in the region during the same period were analyzed. Results Of the 464 relevant studies identified, 23 were included with 592 patients with MIS-C from LAC. Mean age was 6.6 years (IQR, 6–7.4 years);60% were male. The most common clinical manifestations were fever, rash, and conjunctival injection;59% showed Kawasaki disease. Pool proportion of shock was 52%. A total of 47% of patients were admitted to the pediatric intensive care unit (PICU), 23% required mechanical ventilation, and 74% required vasoactive drugs. Intravenous gamma globulin alone was administered in 87% of patients, and in combination with steroids in 60% of cases. Length of hospital stay was 10 days (IQR, 9–10) and PICU stay 5.75 (IQR, 5–6). Overall case fatality ratio was 4% and for those hospitalized in the PICU it was 7%. Conclusion Limited information was available on the clinical outcomes. Improvements in the surveillance system are required to obtain a better epidemiologic overview in the region.

Vaccines to prevent COVID-19: A living systematic review with Trial Sequential Analysis and network meta-analysis of randomized clinical trials.

BACKGROUND: COVID-19 is rapidly spreading causing extensive burdens across the world. Effective vaccines to prevent COVID-19 are urgently needed. METHODS AND FINDINGS: Our objective was to assess the effectiveness and safety of COVID-19 vaccines through analyses of all currently available randomized clinical trials. We searched the databases CENTRAL, MEDLINE, Embase, and other sources from inception to June 17, 2021 for randomized clinical trials assessing vaccines for COVID-19. At least two independent reviewers screened studies, extracted data, and assessed risks of bias. We conducted meta-analyses, network meta-analyses, and Trial Sequential Analyses (TSA). Our primary outcomes included all-cause mortality, vaccine efficacy, and serious adverse events. We assessed the certainty of evidence with GRADE. We identified 46 trials; 35 trials randomizing 219 864 participants could be included in our analyses. Our meta-analyses showed that mRNA vaccines (efficacy, 95% [95% confidence interval (CI), 92% to 97%]; 71 514 participants; 3 trials; moderate certainty); inactivated vaccines (efficacy, 61% [95% CI, 52% to 68%]; 48 029 participants; 3 trials; moderate certainty); protein subunit vaccines (efficacy, 77% [95% CI, -5% to 95%]; 17 737 participants; 2 trials; low certainty); and viral vector vaccines (efficacy 68% [95% CI, 61% to 74%]; 71 401 participants; 5 trials; low certainty) prevented COVID-19. Viral vector vaccines decreased mortality (risk ratio, 0.25 [95% CI 0.09 to 0.67]; 67 563 participants; 3 trials, low certainty), but comparable data on inactivated, mRNA, and protein subunit vaccines were imprecise. None of the vaccines showed evidence of a difference on serious adverse events, but observational evidence suggested rare serious adverse events. All the vaccines increased the risk of non-serious adverse events. CONCLUSIONS: The evidence suggests that all the included vaccines are effective in preventing COVID-19. The mRNA vaccines seem most effective in preventing COVID-19, but viral vector vaccines seem most effective in reducing mortality. Further trials and longer follow-up are necessary to provide better insight into the safety profile of these vaccines.

Implementing Strategies at the Workplace Level to Increase Colorectal Cancer Screening Uptake in Argentina: A Controlled Interrupted Time-series Study.

Colorectal cancer is the third most common neoplasm. The immunochemical fecal occult blood test (iFOBT) is recommended for screening. The worksite setting has great potential to deliver preventive interventions. We aimed to design and evaluate the feasibility and potential impact of a multicomponent strategy in a workplace [Internal Revenue Agency of the Province of Buenos Aires (ARBA from its acronym in Spanish "Agencia de Recaudación de Buenos Aires") in Argentina].We used a quasi-experimental research design, a controlled interrupted time-series (ITS). The study involved: (i) a preintervention period (July 2015-September 2018); and (ii) an intervention period (October 2018-February 2019). We used semi-structured interviews and focus groups to design the intervention and to ensure feasibility and implementability. We fitted segmented linear regression models to evaluate changes in the monthly rates per 10,000 tests done in ARBA employees and controlling for the proportion of tests done in non-ARBA workers. A total of 1,552 ARBA employees aged 50 or more participated. Overall, iFOBT mean uptake rates were 16 times higher in the intervened during the five-month intervention period, remaining statistically significant after adjusting by the proportion of tests done in the control group (P < 0.001). The effect was higher in women aged 50 to 59 years. Activities were suspended due to the COVID-19 pandemic. A multifaceted workplace-based intervention proved to be feasible and acceptable to increase the uptake of colorectal cancer screening in employees of Argentina. Achieving high implementation rates requires building a healthy relationship with the partner organization, adding their values and views, and establishing agreed-upon mechanisms. PREVENTION RELEVANCE: Employee-facing multifaceted worksite cancer screening interventions are a valuable means to increase knowledge and utilization of workers. The controlled ITS showed that colorectal cancer screening mean uptake rates were 16 times higher in the intervened versus the control population during the intervention period, particularly among women aged 50 to 75.

Effect of Calcium Fortified Foods on Health Outcomes: A Systematic Review and Meta-Analysis.

Calcium supplementation and fortification are strategies widely used to prevent adverse outcome in population with low-calcium intake which is highly frequent in low-income settings. We aimed to determine the effectiveness and cost-effectiveness of calcium fortified foods on calcium intake and related health, or economic outcomes. We performed a systematic review and meta-analysis involving participants of any age or gender, drawn from the general population. We searched PubMed, Agricola, EMBASE, CINAHL, Global Health, EconLit, the FAO website and Google until June 2019, without language restrictions. Pair of reviewers independently selected, extracted data and assessed the risk of bias of included studies using Covidence software. Disagreements were resolved by consensus. We performed meta-analyses using RevMan 5.4 and subgroup analyses by study design, age group, and fortification levels. We included 20 studies of which 15 were randomized controlled trials (RCTs), three were non-randomised studies and two were economic evaluations. Most RCTs had high risk of bias on randomization or blinding. Most represented groups were women and children from 1 to 72 months, most common intervention vehicles were milk and bakery products with a fortification levels between 96 and 1200 mg per 100 g of food. Calcium intake increased in the intervention groups between 460 mg (children) and 1200 mg (postmenopausal women). Most marked effects were seen in children. Compared to controls, height increased 0.83 cm (95% CI 0.00; 1.65), plasma parathyroid hormone decreased -1.51 pmol/L, (-2.37; -0.65), urine:calcium creatinine ratio decreased -0.05, (-0.07; -0.03), femoral neck and hip bone mineral density increased 0.02 g/cm2 (0.01; 0.04) and 0.03 g/cm2 (0.00; 0.06), respectively. The largest cost savings (43%) reported from calcium fortification programs came from prevented hip fractures in older women from Germany. Our study highlights that calcium fortification leads to a higher calcium intake, small benefits in children's height and bone health and also important evidence gaps for other outcomes and populations that could be solved with high quality experimental or quasi-experimental studies in relevant groups, especially as some evidence of calcium supplementation show controversial results on the bone health benefit on older adults.

Safety of components and platforms of COVID-19 vaccines considered for use in pregnancy: A rapid review.

BACKGROUND: Rapid assessment of COVID-19 vaccine safety during pregnancy is urgently needed. METHODS: We conducted a rapid systematic review, to evaluate the safety of COVID-19 vaccines selected by the COVID-19 Vaccines Global Access-Maternal Immunization Working Group in August 2020, including their components and their technological platforms used in other vaccines for pregnant persons. We searched literature databases, COVID-19 vaccine pregnancy registries, and explored reference lists from the inception date to February 2021 without language restriction. Pairs of reviewers independently selected studies through COVIDENCE, and performed the data extraction and the risk of bias assessment. Discrepancies were resolved by consensus. Registered on PROSPERO (CRD42021234185). RESULTS: We retrieved 6757 records and 12 COVID-19 pregnancy registries from the search strategy; 38 clinical and non-clinical studies (involving 2,398,855 pregnant persons and 56 pregnant animals) were included. Most studies (89%) were conducted in high-income countries and were cohort studies (57%). Most studies (76%) compared vaccine exposures with no exposure during the three trimesters of pregnancy. The most frequent exposure was to AS03 adjuvant, in the context of A/H1N1 pandemic influenza vaccines, (n = 24) and aluminum-based adjuvants (n = 11). Only one study reported exposure to messenger RNA in lipid nanoparticles COVID-19 vaccines. Except for one preliminary report about A/H1N1 influenza vaccination (adjuvant AS03), corrected by the authors in a more thorough analysis, all studies concluded that there were no safety concerns. CONCLUSION: This rapid review found no evidence of pregnancy-associated safety concerns of COVID-19 vaccines or of their components or platforms when used in other vaccines. However, the need for further data on several vaccine platforms and components is warranted, given their novelty. Our findings support current WHO guidelines recommending that pregnant persons may consider receiving COVID-19 vaccines, particularly if they are at high risk of exposure or have comorbidities that enhance the risk of severe disease.

COVID-19 and pregnancy: An umbrella review of clinical presentation, vertical transmission, and maternal and perinatal outcomes.

BACKGROUND: We conducted an overview of systematic reviews (SRs) summarizing the best evidence regarding the effect of COVID-19 on maternal and child health following Cochrane methods and PRISMA statement for reporting (PROSPERO-CRD42020208783). METHODS: We searched literature databases and COVID-19 research websites from January to October 2020. We selected relevant SRs reporting adequate search strategy, data synthesis, risk of bias assessment, and/or individual description of included studies describing COVID-19 and pregnancy outcomes. Pair of reviewers independently selected studies through COVIDENCE web-software, performed the data extraction, and assessed its quality through the AMSTAR-2 tool. Discrepancies were resolved by consensus. Each SR's results were synthesized and for the most recent, relevant, comprehensive, and with the highest quality, by predefined criteria, we presented GRADE evidence tables. RESULTS: We included 66 SRs of observational studies out of 608 references retrieved and most (61/66) had "critically low" overall quality. We found a relatively low degree of primary study overlap across SRs. The most frequent COVID-19 clinical findings during pregnancy were fever (28-100%), mild respiratory symptoms (20-79%), raised C-reactive protein (28-96%), lymphopenia (34-80%), and pneumonia signs in diagnostic imaging (7-99%). The most frequent maternal outcomes were C-section (23-96%) and preterm delivery (14-64%). Most of their babies were asymptomatic (16-93%) or presented fever (0-50%), low birth weight (5-43%) or preterm delivery (2-69%). The odds ratio (OR) of receiving invasive ventilation for COVID-19 versus non-COVID-19 pregnant women was 1.88 (95% Confidence Interval [CI] 1.36-2.60) and the OR that their babies were admitted to neonatal intensive care unit was 3.13 (95%CI 2.05-4.78). The risk of congenital transmission or via breast milk was estimated to be low, but close contacts may carry risks. CONCLUSION: This comprehensive overview supports that pregnant women with COVID-19 may be at increased risk of adverse pregnancy and birth outcomes and low risk of congenital transmission.

Reflexiones sobre la investigación traslacional en salud y el caso COVID-19 en Argentina

CONICET’s Translational Health Research Network is coordinating efforts to advance in translational medicine. Health researchers initiate and focus their research with the aim of improving the health and quality of life of the population. An efficient research system should address health problems relevant to the population resulting in interventions and outcomes important for patients and health professionals. Recommendations to achieve this involve large thematic areas like (a) to set research priorities;(b) to improve research methodology;(c) to make research management and regulation transparent;(d) to increase accessibility to all results;and (e) to improve research dissemination. The recent COVID-19 pandemic has been a clear demonstration of how the country’s research system has united the most diverse disciplines to jointly provide solutions to address it. An active and transparent mechanism to identify priorities in the country and to unite funding and research efforts to provide solutions to those priorities is proposed. Translational health research means the joint work of the most diverse health research disciplines in order to jointly obtain efficient and effective interventions to improve the health and quality of life of the population.

Reflexiones sobre la investigación traslacional en salud y el caso COVID-19 en Argentina

La Red de Investigación Traslacional en Salud del CONICET está coordinando esfuerzos para avanzar en la medicina traslacional. Los investigadores en salud comienzan y dirigen sus investigaciones con el objetivo de mejorar la salud y calidad de vida de la población. Un sistema de investigación eficiente debe abordar los problemas de salud de importancia para las poblaciones y las intervenciones y resultados que los pacientes y los profesionales de la salud consideren importantes. Las recomendaciones tienen que ver con grandes grupos temáticos que son (a) explicitar la relevancia de la investigación y, por tanto, sus prioridades (b) mejorar la metodología de investigación (c) transparentar la gestión y regulación de la investigación (d) aumentar la accesibilidad a todos los resultados relevantes, y (e) mejorar la manera en que se difunde la investigación. La reciente pandemia de COVID-19 ha sido una clara demostración de cómo el sistema de investigación del país ha unido las más diversas disciplinas para, en forma conjunta, brindar soluciones para enfrentarla. La reciente experiencia consolida que haya un mecanismo activo y transparente de identificación de prioridades en el país y la unión de esfuerzos de financiamiento y de investigadores en brindar soluciones a dichas prioridades. La investigación traslacional en salud significa el trabajo mancomunado de las más diversas disciplinas de investigación en salud para, en forma conjunta, obtener intervenciones eficaces y efectivas que impacten en la mejoría de la salud y la calidad de vida de la población. CONICET's Translational Health Research Network is coordinating efforts to advance in translational medicine. Health researchers initiate and focus their research with the aim of improving the health and quality of life of the population. An efficient research system should address health problems relevant to the population resulting in interventions and outcomes important for patients and health professionals. Recommendations to achieve this involve large thematic areas like (a) to set research priorities;(b) to improve research methodology;(c) to make research management and regulation transparent;(d) to increase accessibility to all results;and (e) to improve research dissemination. The recent COVID-19 pandemic has been a clear demonstration of how the country's research system has united the most diverse disciplines to jointly provide solutions to address it. An active and transparent mechanism to identify priorities in the country and to unite funding and research efforts to provide solutions to those priorities is proposed. Translational health research means the joint work of the most diverse health research disciplines in order to jointly obtain efficient and effective interventions to improve the health and quality of life of the population.