HEARTS in the Americas: Targeting Health System Change to Improve Population Hypertension Control.

PURPOSE OF REVIEW: HEARTS in the Americas is the regional adaptation of Global Hearts, the World Health Organization initiative for cardiovascular disease (CVD) prevention and control. Its overarching goal is to drive health services to change managerial and clinical practice in primary care settings to improve hypertension control and CVD risk management. This review describes the HEARTS in the Americas initiative. First, the regional epidemiological situation of CVD mortality and population hypertension control trends are summarized; then the rationale for its main intervention components: the primary care-oriented management system and the HEARTS Clinical Pathway are described. Finally, the key factors for accelerating the expansion of HEARTS are examined: medicines, team-based care, and a system for monitoring and evaluation. RECENT FINDINGS: Thus far, 33 countries in Latin America and the Caribbean have committed to integrating this program across their primary healthcare network by 2025. The increase in hypertension coverage and control in primary health care settings compared with the traditional model is promising and confirms that the interventions under the HEARTS umbrella are feasible and acceptable to communities, patients, providers, decision-makers, and funders. This review highlights some cases of successful implementation. Scaling up effective treatment for hypertension and optimization of CVD risk management is a pragmatic way to accelerate the reduction of CVD mortality while strengthening primary healthcare systems to respond effectively, with quality, and equitably, to the challenge of non-communicable diseases, not only in low-middle income countries but in all communities globally.

[HEARTS in the Americas: targeting health system change to improve population hypertension controlHEARTS nas Américas: impulsionar mudanças no sistema de saúde para melhorar o controle da hipertensão arterial na população]. / HEARTS en las Américas: impulsar el cambio en el sistema de salud para mejorar el control de la hipertensión en la población.

Purpose of review: HEARTS in the Americas is the regional adaptation of Global Hearts, the World Health Organization initiative for cardiovascular disease (CVD) prevention and control. Its overarching goal is to drive health services to change managerial and clinical practice in primary care settings to improve hypertension control and CVD risk management. This review describes the HEARTS in the Americas initiative. First, the regional epidemiological situation of CVD mortality and population hypertension control trends are summarized; then the rationale for its main intervention components: the primary care-oriented management system and the HEARTS Clinical Pathway are described. Finally, the key factors for accelerating the expansion of HEARTS are examined: medicines, team-based care, and a system for monitoring and evaluation. Recent findings: Thus far, 33 countries in Latin America and the Caribbean have committed to integrating this program across their primary healthcare network by 2025. The increase in hypertension coverage and control in primary health care settings compared with the traditional model is promising and confirms that the interventions under the HEARTS umbrella are feasible and acceptable to communities, patients, providers, decision-makers, and funders. This review highlights some cases of successful implementation. Summary: Scaling up effective treatment for hypertension and optimization of CVD risk management is a pragmatic way to accelerate the reduction of CVD mortality while strengthening primary healthcare systems to respond effectively, with quality, and equitably, to the challenge of non-communicable diseases, not only in low-middle income countries but in all communities globally.

Propósito da revisão: HEARTS nas Américas é uma adaptação regional da iniciativa mundial HEARTS, da Organização Mundial da Saúde, voltada para prevenção e controle das doenças cardiovasculares (DCV) na Região das Américas. Seu objetivo geral é promover mudanças na prática clínica e na gestão da atenção primária pelos serviços de saúde a fim de melhorar o controle da hipertensão arterial e reduzir o risco de DCV. Esta revisão descreve a iniciativa HEARTS nas Américas. Primeiro, é apresentado um resumo da situação epidemiológica regional relativa à mortalidade por DCV e das tendências no controle da hipertensão arterial em nível populacional. Em seguida, são explicados os motivos por trás dos principais componentes da intervenção: o sistema de manejo focado na atenção primária e o componente clínico da HEARTS. Por fim, são examinados os principais fatores para acelerar a ampliação da HEARTS: medicamentos, atenção baseada no trabalho em equipe e um sistema de monitoramento e avaliação. Resultados recentes: Até o momento, 33 países e territórios da América Latina e do Caribe se comprometeram a integrar esse programa em toda sua rede de atenção primária à saúde até 2025. Comparado com o modelo tradicional, o aumento da cobertura e do controle da hipertensão arterial nos ambientes de atenção primária à saúde é promissor e confirma que as intervenções promovidas pela HEARTS são exequíveis e aceitas por comunidades, pacientes, prestadores de serviços de saúde, tomadores de decisão e financiadores. Nesta revisão, destacamos alguns casos nos quais a implementação foi satisfatória. Conclusões: Ampliar a aplicação de um tratamento eficaz contra a hipertensão arterial e otimizar o controle do risco de DCV são medidas pragmáticas para acelerar a redução da mortalidade por DCV e, ao mesmo tempo, fortalecer os sistemas de atenção primária à saúde para responder com qualidade, eficácia e equidade ao desafio apresentado pelas doenças não transmissíveis, não apenas nos países de baixa ou média renda, mas no mundo todo.

Deconstructing virus condensation.

Viruses have evolved precise mechanisms for using the cellular physiological pathways for their perpetuation. These virus-driven biochemical events must be separated in space and time from those of the host cell. In recent years, granular structures, known for over a century for rabies virus, were shown to host viral gene function and were named using terms such as viroplasms, replication sites, inclusion bodies, or viral factories (VFs). More recently, these VFs were shown to be liquid-like, sharing properties with membrane-less organelles driven by liquid-liquid phase separation (LLPS) in a process widely referred to as biomolecular condensation. Some of the best described examples of these structures come from negative stranded RNA viruses, where micrometer size VFs are formed toward the end of the infectious cycle. We here discuss some basic principles of LLPS in connection with several examples of VFs and propose a view, which integrates viral replication mechanisms with the biochemistry underlying liquid-like organelles. In this view, viral protein and RNA components gradually accumulate up to a critical point during infection where phase separation is triggered. This yields an increase in transcription that leads in turn to increased translation and a consequent growth of initially formed condensates. According to chemical principles behind phase separation, an increase in the concentration of components increases the size of the condensate. A positive feedback cycle would thus generate in which crucial components, in particular nucleoproteins and viral polymerases, reach their highest levels required for genome replication. Progress in understanding viral biomolecular condensation leads to exploration of novel therapeutics. Furthermore, it provides insights into the fundamentals of phase separation in the regulation of cellular gene function given that virus replication and transcription, in particular those requiring host polymerases, are governed by the same biochemical principles.

[Association between population hypertension control and ischemic heart disease and stroke mortality in 36 countries of the Americas, 1990-2019: an ecological studyAssociação entre controle populacional da hipertensão e mortalidade por doença cardíaca isquêmica e acidente vascular cerebral em 36 países das Américas, 1990-2019: um estudo ecológico]. / Asociación entre el control de la hipertensión arterial en la población y la mortalidad por cardiopatía isquémica y accidente cerebrovascular en 36 países y territorios de la Región de las Américas, 1990-2019: un estudio ecológico.

Objective: To quantify the association between the prevalence of population hypertension control and ischemic heart disease (IHD) and stroke mortality in 36 countries of the Americas from 1990 to 2019. Methods: This ecologic study uses the prevalence of hypertension, awareness, treatment, and control from the NCD-RisC and IHD and stroke mortality from the Global Burden of Disease Study 2019. Regression analysis was used to assess time trends and the association between population hypertension control and mortality. Results: Between 1990 and 2019, age-standardized death rates due to IHD and stroke declined annually by 2.2% (95% confidence intervals: -2.4 to -2.1) and 1.8% (-1.9 to -1.6), respectively. The annual reduction rate in IHD and stroke mortality deaccelerated to -1% (-1.2 to -0.8) during 2000-2019. From 1990 to 2019, the prevalence of hypertension controlled to a systolic/diastolic blood pressure ≤140/90 mmHg increased by 3.2% (3.1 to 3.2) annually. Population hypertension control showed an inverse association with IHD and stroke mortality, respectively, regionwide and in all but 3 out of 36 countries. Regionwide, for every 1% increase in population hypertension control, our data predicted a reduction of 2.9% (-2.94 to -2.85) in IHD deaths per 100 000 population, equivalent to an averted 25 639 deaths (2.5 deaths per 100 000 population) and 2.37% (-2.41 to -2.33) in stroke deaths per 100 000 population, equivalent to an averted 9 650 deaths (1 death per 100 000 population). Conclusion: There is a strong ecological negative association between IHD and stroke mortality and population hypertension control. Countries with the best performance in hypertension control showed better progress in reducing CVD mortality. Prediction models have implications for hypertension management in most populations in the Region of the Americas and other parts of the world.

Objetivo: Quantificar a associação entre a prevalência de controle populacional da hipertensão e mortalidade por doença cardíaca isquêmica (DCI) e acidente vascular cerebral (AVC) em 36 países das Américas, de 1990 a 2019. Métodos: Este estudo ecológico utilizou os dados de prevalência da hipertensão e prevalência da detecção, tratamento e controle populacional da hipertensão do estudo NCD-RisC, e de mortalidade por DCI e AVC do Estudo de Carga Global de Doença de 2019. Análise de regressão foi utilizada para avaliar as tendências no tempo e a associação entre controle populacional da hipertensão e mortalidade. Resultados: Entre 1990 e 2019, as taxas de mortalidade padronizadas por idade devidas a DCI e AVC diminuíram anualmente 2,2% (intervalos de confiança de 95%: −2,4 a −2,1) e 1,8% (−1,9 a −1,6), respectivamente. A taxa anual de redução na mortalidade por DCI e AVC desacelerou para −1% (−1,2 a −0,8) durante o período de 2000-2019. De 1990 a 2019, a prevalência de hipertensão controlada com pressão arterial sistólica/diastólica ≤140/90 mmHg apresentou aumento anual de 3,2% (3,1 a 3,2). O controle populacional da hipertensão apresentou associação inversa com mortalidade por DCI e AVC, respectivamente, em toda a região, e em todos os 36 países, com a exceção de três. Em toda a região, para cada 1% de aumento no controle populacional da hipertensão, nossos dados previram uma redução de 2,9% (−2,94 a −2,85) nos óbitos por DCI por 100 000 habitantes, equivalente à prevenção de 25 639 óbitos (2,5 óbitos por 100 000 habitantes), e de 2,37% (−2,41 a −2,33) nos óbitos por AVC por 100 000 habitantes, equivalente à prevenção de 9 650 óbitos (1 óbito por 100 000 habitantes). Conclusão: Existe forte associação ecológica negativa entre mortalidade por DCI e AVC e controle populacional da hipertensão. Os países com o melhor desempenho no controle da hipertensão mostraram melhor progresso na redução da mortalidade por doenças cardiovasculares. Os modelos de previsão têm implicações no controle da hipertensão na maioria das populações da Região das Américas e em outras partes do mundo.

Noncommunicable diseases in the Americas: a review of the Pan American Health Organization's 25-year program of work.

This article describes progress in tackling noncommunicable diseases (NCDs) in the Americas since the Pan American Health Organization (PAHO) started its NCD program 25 years ago. Changes in the epidemiology of NCDs, NCD policies, health service capacity, and surveillance are discussed. PAHO's NCD program is guided by regional plans of action on specific NCDs and risk factors, as well as a comprehensive NCD plan. Its work involves implementing evidence-based World Health Organization technical packages on NCDs and their risk factors with the aim of achieving the Sustainable Development Goal target of a one third reduction in premature mortality caused by NCDs by 2030. Important advances have been made in the past 25 years in implementation of: policies on NCD risk factors; interventions to improve NCD diagnosis and treatment; and NCD surveillance. Premature mortality from NCDs decreased by 1.7% a year between 2000 and 2011 and 0.77% a year between 2011 and 2019. However, policies on risk factor prevention and health promotion need to be strengthened to ensure more countries are on track to achieving the NCD-related health goals of the Sustainable Development Goals by 2030. Actions are recommended for governments to raise the priority of NCDs by: making NCDs a core pillar of primary care services, using revenues from health taxes to invest more in NCD prevention and control; and implementing policies, laws, and regulations to reduce the demand for and availability of tobacco, alcohol, and ultra-processed food products.

En este artículo se describe el progreso en la lucha contra las enfermedades no transmisibles (ENT) en la Región de las Américas desde que la Organización Panamericana de la Salud (OPS) iniciara su programa contra las ENT hace 25 años. Se abordan los cambios en las características epidemiológicas, las políticas, la capacidad de los servicios de salud y la vigilancia de estas enfermedades. Este programa de la OPS se rige por planes regionales de acción sobre enfermedades y factores de riesgo específicos, así como por un plan integral de ENT. Su labor consiste en poner en práctica paquetes técnicos de la Organización Mundial de la Salud basados en la evidencia sobre las ENT y sus factores de riesgo con el objetivo de alcanzar la meta de los Objetivos de Desarrollo Sostenible (ODS) de reducir en un tercio la mortalidad prematura causada por las ENT para el 2030. En los últimos 25 años se han logrado importantes avances en la ejecución de políticas sobre los factores de riesgo de estas enfermedades, en las intervenciones para mejorar su diagnóstico y tratamiento, y en la vigilancia. La mortalidad prematura por ENT disminuyó 1,7% anual entre el 2000 y el 2011 y 0,77% anual entre los años 2011 y 2019. Sin embargo, es necesario fortalecer las políticas de prevención de factores de riesgo y promoción de la salud para garantizar que más países estén bien encaminados para lograr las metas de salud de los ODS relacionadas con las ENT para el 2030. Se recomiendan medidas para que los gobiernos prioricen más las ENT y las conviertan en un pilar central de los servicios de atención primaria, al usar los ingresos generados por los impuestos en el sector de la salud para incrementar las inversiones en la prevención y control de las ENT, y ejecutar políticas, leyes y regulaciones para reducir la demanda y la disponibilidad de tabaco, alcohol y alimentos ultraprocesados.

Este artigo descreve o progresso no combate às doenças não transmissíveis (DNTs) nas Américas desde que a Organização Pan-Americana da Saúde (OPAS) iniciou seu programa para essas doenças há 25 anos. Discute-se como evoluíram a epidemiologia das DNTs, as políticas contra essas doenças, a capacidade dos serviços de saúde e a vigilância. O programa da OPAS para as DNTs é orientado por planos de ação regionais sobre DNTs específicas e fatores de risco, bem como por um plano integral contra essas doenças. O trabalho envolve a implementação de pacotes técnicos da Organização Mundial da Saúde baseados em evidências sobre as DNTs e seus fatores de risco, no intuito de alcançar a meta do Objetivo de Desenvolvimento Sustentável de reduzir em um terço a mortalidade prematura causada pelas DNTs até 2030. Avanços importantes foram obtidos nos últimos 25 anos na implementação de políticas sobre fatores de risco das DNTs, intervenções para melhorar o diagnóstico e o tratamento das DNTs, e vigilância das DNTs. A mortalidade prematura causada pelas DNTs diminuiu 1,7% ao ano entre 2000 e 2011 e 0,77% ao ano entre 2011 e 2019. Contudo, as políticas sobre a prevenção dos fatores de risco e a promoção da saúde precisam ser fortalecidas para que mais países estejam no rumo certo para alcançar as metas de saúde relacionadas a essas doenças, no âmbito dos Objetivos de Desenvolvimento Sustentável até 2030. São recomendadas medidas para que os governos elevem a prioridade das DNTs ao torná-las um pilar central dos serviços de atenção primária, usando a receita dos tributos saudáveis para investir mais na prevenção e no controle das DNTs, e ao implementar políticas, leis e regulamentos para reduzir a demanda e a disponibilidade de álcool, tabaco e produtos alimentícios ultraprocessados.

[Monitoring and evaluation platform for HEARTS in the Americas: improving population-based hypertension control programs in primary health carePlataforma de monitoramento e avaliação do programa HEARTS nas Américas: melhoria dos programas de controle da hipertensão de base populacional na atenção primária à saúde]. / Plataforma de monitoreo y evaluación para HEARTS en las Américas: hacia la mejora de los programas de control de la hipertensión a nivel poblacional en la atención primaria de salud.

HEARTS in the Americas is the Pan American Health Organization flagship program to accelerate the reduction of the cardiovascular disease (CVD) burden by improving hypertension control and CVD secondary prevention in primary health care. A monitoring and evaluation (M&E) platform is needed for program implementation, benchmarking, and informing policy-makers. This paper describes the conceptual bases of the HEARTS M&E platform including software design principles, contextualization of data collection modules, data structure, reporting, and visualization. The District Health Information Software 2 (DHIS2) web-based platform was chosen to implement aggregate data entry of CVD outcome, process, and structural risk factor indicators. In addition, PowerBI was chosen for data visualization and dashboarding for the analysis of performance and trends above the health care facility level. The development of this new information platform was focused on primary health care facility data entry, timely data reporting, visualizations, and ultimately active use of data to drive decision-making for equitable program implementation and improved quality of care. Additionally, lessons learnt and programmatic considerations were assessed through the experience of the M&E software development. Building political will and support is essential to developing and deploying a flexible platform in multiple countries which is contextually specific to the needs of various stakeholders and levels of the health care system. The HEARTS M&E platform supports program implementation and reveals structural and managerial limitations and care gaps. The HEARTS M&E platform will be central to monitoring and driving further population-level improvements in CVD and other noncommunicable disease-related health.

A iniciativa HEARTS nas Américas é o principal programa da Organização Pan-Americana da Saúde para acelerar a redução da carga de doenças cardiovasculares (DCV) por meio do melhoramento do controle da hipertensão e da prevenção secundária de DCV na atenção primária à saúde. Uma plataforma de monitoramento e avaliação (M&E, na sigla em inglês) é necessária para a implementação do programa, para fazer a avaliação comparativa e para informar os formuladores de políticas. Este documento descreve as bases conceituais da plataforma de M&E do HEARTS, incluindo princípios de design de software, contextualização dos módulos de coleta de dados, estrutura de dados, relatórios e visualização. A plataforma baseada na web do District Health Information Software 2 (DHIS2) foi escolhida para implementar a inserção de dados agregados de indicadores de fatores de risco estruturais, processos e desfechos de DCV. Além disso, o PowerBI foi escolhido para a visualização de dados e para fazer o dashboard da análise de desempenho e tendências para além do nível da unidade de saúde. O desenvolvimento desta nova plataforma de informações teve como foco a inserção de dados da unidade de atenção primária à saúde, a notificação oportuna de dados, visualizações e o uso ativo dos dados para orientar a tomada de decisões para a implementação equitativa do programa e a melhoria da qualidade do atendimento. Além disso, as lições aprendidas e as considerações programáticas foram avaliadas por meio da experiência do desenvolvimento do software de M&E. Fomentar vontade política e apoio é essencial para desenvolver e implantar uma plataforma flexível em vários países, que seja contextualmente específica para as necessidades das diferentes partes interessadas e níveis do sistema de saúde. A plataforma de M&E do HEARTS ampara a implementação do programa e revela limitações estruturais e gerenciais, bem como lacunas na atenção à saúde. A plataforma de M&E do HEARTS será central para monitorar e impulsionar mais melhorias no nível populacional em DCV e outras doenças não transmissíveis.

Airway Complications in Pregnant Patients Undergoing Electroconvulsive Therapy: A Retrospective Case-Control Study.

OBJECTIVES: Electroconvulsive therapy (ECT) is an evidence-based treatment for severe depression and bipolar disorder in pregnant women. Electroconvulsive therapy involves induction of general anesthesia, muscle relaxation, and positive-pressure ventilation. Airway manipulation may lead to complications such as vocal cord injury, aspiration, inability to ventilate, and death. The purpose of this study was to determine whether there were differences in the incidence of airway complications in pregnant patients who underwent mask ventilation (MV) versus endotracheal intubation (ETI) compared with nonpregnant control subjects. METHODS: We conducted a single-center retrospective chart review of all adult pregnant patients who underwent anesthesia for ECT from June 1, 2011, to June 30, 2020. Each ECT treatment delivered to a pregnant patient was matched with 2 ECT treatments delivered to a nonpregnant female control subject. Charts were queried for airway management (MV vs ETI), gestational age, and airway complications. Each ECT treatment was considered an independent event. RESULTS: Seventy-six ECT treatments from 11 pregnant patients were matched with 154 ECT treatments from 13 nonpregnant patients. In pregnant patients, airway management consisted of MV in 57 of the 76 treatments: 12 of 12 in the first trimester, 33 of 44 in the second trimester, and 12 of 20 in the third trimester. All 154 ECT treatments in the control group used MV. No airway complications were experienced in pregnant or nonpregnant patients with MV or ETI. CONCLUSIONS: No airway complications were observed in pregnant patients undergoing MV or ETI regardless of gestational age.

Stroke-derived neutrophils demonstrate higher formation potential and impaired resolution of CD66b + driven neutrophil extracellular traps.

BACKGROUND: Recent evidence suggests a merging role of immunothrombosis in the formation of arterial thrombosis. Our study aims to investigate its relevance in stroke patients. METHODS: We compared the peripheral immunological profile of stroke patients vs. healthy controls. Serum samples were functionally analyzed for their formation and clearance of Neutrophil-Extracellular-Traps. The composition of retrieved thrombi has been immunologically analyzed. RESULTS: Peripheral blood of stroke patients showed significantly elevated levels of DNAse-I (p < 0.001), LDG (p = 0.003), CD4 (p = 0.005) as well as the pro-inflammatory cytokines IL-17 (p < 0.001), INF-γ (p < 0.001) and IL-22 (p < 0.001) compared to controls, reflecting a TH1/TH17 response. Increased counts of DNAse-I in sera (p = 0.045) and Neutrophil-Extracellular-Traps in thrombi (p = 0.032) have been observed in patients with onset time of symptoms longer than 4,5 h. Lower values of CD66b in thrombi were independently associated with greater improvement of NIHSS after mechanical thrombectomy (p = 0.045). Stroke-derived neutrophils show higher potential for Neutrophil-Extracellular-Traps formation after stimulation and worse resolution under DNAse-I treatment compared to neutrophils derived from healthy individuals. CONCLUSIONS: Our data provide new insight in the role of activated neutrophils and Neutrophil-Extracellular-Traps in ischemic stroke. Future larger studies are warranted to further investigate the role of immunothrombosis in the cascades of stroke. TRIAL REGISTRATION: DRKS, DRKS00013278, Registered 15 November 2017, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00013278.

Intermittent rolling is a defect of the extravasation cascade caused by Myosin1e-deficiency in neutrophils.

Neutrophil extravasation is a migratory event in response to inflammation that depends on cytoskeletal dynamics regulated by myosins. Myosin-1e (Myo1e) is a long-tailed class-I myosin that has not yet been studied in the context of neutrophil-endothelial interactions and neutrophil extravasation. Intravital microscopy of TNFα-inflamed cremaster muscles in Myo1e-deficient mice revealed that Myo1e is required for efficient neutrophil extravasation. Specifically, Myo1e deficiency caused increased rolling velocity, decreased firm adhesion, aberrant crawling, and strongly reduced transmigration. Interestingly, we observed a striking discontinuous rolling behavior termed "intermittent rolling," during which Myo1e-deficient neutrophils showed alternating rolling and jumping movements. Surprisingly, chimeric mice revealed that these effects were due to Myo1e deficiency in leukocytes. Vascular permeability was not significantly altered in Myo1e KO mice. Myo1e-deficient neutrophils showed diminished arrest, spreading, uropod formation, and chemotaxis due to defective actin polymerization and integrin activation. In conclusion, Myo1e critically regulates adhesive interactions of neutrophils with the vascular endothelium and neutrophil extravasation. Myo1e may therefore be an interesting target in chronic inflammatory diseases characterized by excessive neutrophil recruitment.

Four reasons for adopting a life course approach to health in the COVID-19 era and beyond.

The life course approach effectively responds to pressing health needs and fills critical gaps to improve health outcomes in the era of COVID-19 and beyond. This article outlines four main reasons to adopt and implement the life course approach in public health at national and local levels: (i) the approach effectively responds to new health trends and evidence, (ii) it fills longstanding gaps in care, (iii) it best addresses health inequities, and (iv) it can help achieve more with less.

El enfoque del curso de vida da respuestas eficaces a las urgentes necesidades de salud y salva brechas críticas para mejorar los resultados de salud en la era de la COVID-19 y los años posteriores. En este artículo se describen las cuatro razones principales para adoptar y poner en práctica el enfoque del curso de vida en la salud pública a nivel local y nacional: este enfoque (i) da respuestas eficaces a las tendencias y la evidencia nuevas en el ámbito de la salud, (ii) salva brechas de larga data en la atención, (iii) aborda de la mejor manera posible las inequidades de salud, y (iv) puede contribuir a lograr más con menos recursos.

A abordagem de curso de vida responde de forma efetiva a necessidades urgentes de saúde e preenche lacunas críticas para melhorar os resultados de saúde na era da COVID-19 e mais além. Este artigo descreve quatro motivos principais para adotar e implementar a abordagem de curso de vida na saúde pública em nível nacional e local: (i) a abordagem responde de forma efetiva a novas evidências e tendências em saúde, (ii) preenche lacunas antigas nos cuidados de saúde, (iii) lida melhor com iniquidades em saúde e (iv) pode ajudar a conquistar mais com menos recursos.

Association between population hypertension control and ischemic heart disease and stroke mortality in 36 countries of the Americas, 1990-2019: an ecological study.

Objective: To quantify the association between the prevalence of population hypertension control and ischemic heart disease (IHD) and stroke mortality in 36 countries of the Americas from 1990 to 2019. Methods: This ecologic study uses the prevalence of hypertension, awareness, treatment, and control from the NCD-RisC and IHD and stroke mortality from the Global Burden of Disease Study 2019. Regression analysis was used to assess time trends and the association between population hypertension control and mortality. Results: Between 1990 and 2019, age-standardized death rates due to IHD and stroke declined annually by 2.2% (95% confidence intervals: -2.4 to -2.1) and 1.8% (-1.9 to -1.6), respectively. The annual reduction rate in IHD and stroke mortality deaccelerated to -1% (-1.2 to -0.8) during 2000-2019. From 1990 to 2019, the prevalence of hypertension controlled to a systolic/diastolic blood pressure ≤140/90 mmHg increased by 3.2% (3.1 to 3.2) annually. Population hypertension control showed an inverse association with IHD and stroke mortality, respectively, regionwide and in all but 3 out of 36 countries. Regionwide, for every 1% increase in population hypertension control, our data predicted a reduction of 2.9% (-2.94 to -2.85) in IHD deaths per 100 000 population, equivalent to an averted 25 639 deaths (2.5 deaths per 100 000 population) and 2.37% (-2.41 to -2.33) in stroke deaths per 100 000 population, equivalent to an averted 9 650 deaths (1 death per 100 000 population). Conclusion: There is a strong ecological negative association between IHD and stroke mortality and population hypertension control. Countries with the best performance in hypertension control showed better progress in reducing CVD mortality. Prediction models have implications for hypertension management in most populations in the Region of the Americas and other parts of the world.

Monitoring and evaluation platform for HEARTS in the Americas: improving population-based hypertension control programs in primary health care.

HEARTS in the Americas is the Pan American Health Organization flagship program to accelerate the reduction of the cardiovascular disease (CVD) burden by improving hypertension control and CVD secondary prevention in primary health care. A monitoring and evaluation (M&E) platform is needed for program implementation, benchmarking, and informing policy-makers. This paper describes the conceptual bases of the HEARTS M&E platform including software design principles, contextualization of data collection modules, data structure, reporting, and visualization. The District Health Information Software 2 (DHIS2) web-based platform was chosen to implement aggregate data entry of CVD outcome, process, and structural risk factor indicators. In addition, PowerBI was chosen for data visualization and dashboarding for the analysis of performance and trends above the health care facility level. The development of this new information platform was focused on primary health care facility data entry, timely data reporting, visualizations, and ultimately active use of data to drive decision-making for equitable program implementation and improved quality of care. Additionally, lessons learnt and programmatic considerations were assessed through the experience of the M&E software development. Building political will and support is essential to developing and deploying a flexible platform in multiple countries which is contextually specific to the needs of various stakeholders and levels of the health care system. The HEARTS M&E platform supports program implementation and reveals structural and managerial limitations and care gaps. The HEARTS M&E platform will be central to monitoring and driving further population-level improvements in CVD and other noncommunicable disease-related health.

HEARTS en las Américas es el programa insignia de la Organización Panamericana de la Salud para acelerar la reducción de la carga de enfermedades cardiovasculares (ECV) mediante la mejora del control de la hipertensión y la prevención secundaria de las ECV en la atención primaria de salud. Es necesaria una plataforma de monitoreo y evaluación (M&E) para ejecutar el programa, establecer puntos de referencia y notificar a los responsables de las políticas. En este artículo se describen las bases conceptuales de la plataforma HEARTS M&E, como los principios de diseño del software, la contextualización de los módulos de recopilación de datos, la estructura de los datos, la presentación de información y la visualización. Se escogió la plataforma web District Health Information Software 2 (DHIS2) para ejecutar el ingreso de los datos agregados de los indicadores de resultados, procesos y factores de riesgo estructurales de las ECV. Además, se eligió PowerBI para la visualización de datos y la elaboración del panel de control para el análisis del desempeño y las tendencias más allá del nivel de los centros de atención médica. El desarrollo de esta nueva plataforma de información se centró en el ingreso de datos de los centros de atención primaria de salud, la presentación oportuna de datos, las visualizaciones y, en última instancia, el uso activo de los datos para impulsar la toma de decisiones en la ejecución equitativa del programa y la mejora de calidad de la atención. Además, se evaluaron las enseñanzas extraídas y las consideraciones programáticas con la experiencia del desarrollo de software de M&E. Lograr el apoyo y la voluntad política es esencial para desarrollar y poner en marcha una plataforma flexible en múltiples países que sea contextualmente específica según las necesidades de las diversas partes interesadas y los niveles del sistema de atención de la salud. La plataforma HEARTS M&E brinda apoyo para la ejecución del programa y muestra las limitaciones estructurales y gerenciales, así como las brechas en la atención. Esta plataforma será fundamental para monitorear e impulsar nuevas mejoras a nivel de la población en lo que respecta a las ECV y otras enfermedades no transmisibles relacionadas.

A iniciativa HEARTS nas Américas é o principal programa da Organização Pan-Americana da Saúde para acelerar a redução da carga de doenças cardiovasculares (DCV) por meio do melhoramento do controle da hipertensão e da prevenção secundária de DCV na atenção primária à saúde. Uma plataforma de monitoramento e avaliação (M&E, na sigla em inglês) é necessária para a implementação do programa, para fazer a avaliação comparativa e para informar os formuladores de políticas. Este documento descreve as bases conceituais da plataforma de M&E do HEARTS, incluindo princípios de design de software, contextualização dos módulos de coleta de dados, estrutura de dados, relatórios e visualização. A plataforma baseada na web do District Health Information Software 2 (DHIS2) foi escolhida para implementar a inserção de dados agregados de indicadores de fatores de risco estruturais, processos e desfechos de DCV. Além disso, o PowerBI foi escolhido para a visualização de dados e para fazer o dashboard da análise de desempenho e tendências para além do nível da unidade de saúde. O desenvolvimento desta nova plataforma de informações teve como foco a inserção de dados da unidade de atenção primária à saúde, a notificação oportuna de dados, visualizações e o uso ativo dos dados para orientar a tomada de decisões para a implementação equitativa do programa e a melhoria da qualidade do atendimento. Além disso, as lições aprendidas e as considerações programáticas foram avaliadas por meio da experiência do desenvolvimento do software de M&E. Fomentar vontade política e apoio é essencial para desenvolver e implantar uma plataforma flexível em vários países, que seja contextualmente específica para as necessidades das diferentes partes interessadas e níveis do sistema de saúde. A plataforma de M&E do HEARTS ampara a implementação do programa e revela limitações estruturais e gerenciais, bem como lacunas na atenção à saúde. A plataforma de M&E do HEARTS será central para monitorar e impulsionar mais melhorias no nível populacional em DCV e outras doenças não transmissíveis.

HEARTS in the Americas: innovations for improving hypertension and cardiovascular disease risk management in primary care.

Global Hearts is the flagship initiative of the World Health Organization to reduce the burden of cardiovascular diseases, the leading cause of death and disability worldwide. HEARTS in the Americas Initiative is the regional adaptation that envisions HEARTS as the model for cardiovascular disease risk management, including hypertension and diabetes, in primary health care in the Americas by 2025. This initiative is entering its sixth year of implementation and now includes 22 countries and 1 380 primary health care centers. The objectives of this report are three-fold. First, it describes the emergence and the main elements of HEARTS in the Americas. Secondly, it summarizes the main innovations developed to catalyze and sustain implementation of the initiative. These innovations include: a) introduction of hypertension control drivers; b) development of a comprehensive and practical clinical pathway; c) development of a strategy to improve the accuracy of blood pressure measurement; d) creation of a monitoring and evaluation platform; and e) development of a standardized set of training and education resources. Thirdly, this report discusses future priorities of the initiative. The goal of implementing these innovative and pragmatic solutions is to create a more effective health system and shift the focus of cardiovascular and hypertension programs from the highly specialized care level to primary health care. In addition, HEARTS in the Americas can serve as a model for more comprehensive, effective, and sustainable noncommunicable disease prevention and treatment practices.

Global Hearts es la iniciativa emblemática de la Organización Mundial de la Salud para reducir la carga de las enfermedades cardiovasculares, la principal causa de muerte y discapacidad en todo el mundo. La iniciativa HEARTS en las Américas es la adaptación regional que propone HEARTS como modelo para el manejo del riesgo de enfermedades cardiovasculares, incluida la hipertensión, y la diabetes en la atención primaria de salud en la Región de las Américas para el año 2025. Esta iniciativa está iniciando su sexto año de aplicación y ya incluye a 22 países y 1 380 centros de atención primaria de salud. Son tres los objetivos de este informe. En primer lugar, describir cómo surgió la iniciativa HEARTS en las Américas y cuáles son sus principales elementos. En segundo lugar, resumir las principales innovaciones logradas para catalizar la iniciativa y mantener su aplicación. Entre estas innovaciones se encuentran: a) la introducción de factores impulsores del control de la hipertensión; b) el desarrollo de una vía clínica integral y práctica; c) la elaboración de una estrategia para mejorar la precisión de la medición de la presión arterial; d) la creación de un marco de seguimiento y evaluación; y e) la elaboración de un conjunto estandarizado de recursos de capacitación y formación. En tercer lugar, en este informe se examinan las futuras prioridades de la iniciativa. El objetivo de poner en marcha estas soluciones innovadoras y pragmáticas es crear un sistema de salud más efectivo y trasladar el enfoque de los programas cardiovasculares y de hipertensión del nivel de atención altamente especializada a la atención primaria de salud. Además, HEARTS en las Américas puede servir como modelo para unas prácticas más integrales, efectivas y sostenibles en la prevención y el tratamiento de las enfermedades no transmisibles.

Global Hearts é a iniciativa mais importante da Organização Mundial da Saúde para reduzir a carga de doenças cardiovasculares, que são a principal causa de morte e incapacidade em todo o mundo. A iniciativa HEARTS nas Américas é a adaptação regional que pressupõe a HEARTS como o modelo para a gestão do risco de doenças cardiovasculares, incluindo hipertensão e diabetes, na atenção primária à saúde nas Américas até 2025. Essa iniciativa está entrando em seu sexto ano de implementação e agora inclui 22 países e 1 380 centros de atenção primária à saúde. Os objetivos deste relatório são três. Primeiramente, ele descreve o surgimento e os principais elementos da iniciativa HEARTS nas Américas. Em segundo lugar, resume as principais inovações desenvolvidas para catalisar e sustentar a implementação da iniciativa. Essas inovações incluem: a) introdução de fatores impulsionadores de controle da hipertensão; b) desenvolvimento de um caminho clínico abrangente e prático; c) desenvolvimento de uma estratégia para melhorar a exatidão da aferição da pressão arterial; d) criação de uma plataforma de monitoramento e avaliação; e e) desenvolvimento de um conjunto padronizado de recursos para treinamento e educação. Em terceiro lugar, este relatório discute as futuras prioridades da iniciativa. O objetivo de implementar essas soluções inovadoras e pragmáticas é criar um sistema de saúde mais eficaz e mudar o foco dos programas cardiovasculares e de hipertensão do nível de atendimento altamente especializado para a atenção primária à saúde. Além disso, a iniciativa HEARTS nas Américas pode servir de modelo para práticas mais abrangentes, efetivas e sustentáveis de prevenção e tratamento de doenças não transmissíveis.

[HEARTS in the Americas: innovations for improving hypertension and cardiovascular disease risk management in primary careHEARTS nas Américas: inovações para melhorar a gestão do risco de hipertensão e de doenças cardiovasculares na atenção primária]. / HEARTS en las Américas: innovaciones para mejorar el manejo de la hipertensión y del riesgo cardiovascular en la atención primaria.

Global Hearts is the flagship initiative of the World Health Organization to reduce the burden of cardiovascular diseases, the leading cause of death and disability worldwide. HEARTS in the Americas Initiative is the regional adaptation that envisions HEARTS as the model for cardiovascular disease risk management, including hypertension and diabetes, in primary health care in the Americas by 2025. This initiative is entering its sixth year of implementation and now includes 22 countries and 1 380 primary health care centers. The objectives of this report are three-fold. First, it describes the emergence and the main elements of HEARTS in the Americas. Secondly, it summarizes the main innovations developed to catalyze and sustain implementation of the initiative. These innovations include: a) introduction of hypertension control drivers; b) development of a comprehensive and practical clinical pathway; c) development of a strategy to improve the accuracy of blood pressure measurement; d) creation of a monitoring and evaluation platform; and e) development of a standardized set of training and education resources. Thirdly, this report discusses future priorities of the initiative. The goal of implementing these innovative and pragmatic solutions is to create a more effective health system and shift the focus of cardiovascular and hypertension programs from the highly specialized care level to primary health care. In addition, HEARTS in the Americas can serve as a model for more comprehensive, effective, and sustainable noncommunicable disease prevention and treatment practices.

Global Hearts é a iniciativa mais importante da Organização Mundial da Saúde para reduzir a carga de doenças cardiovasculares, que são a principal causa de morte e incapacidade em todo o mundo. A Iniciativa HEARTS nas Américas é a adaptação regional que pressupõe a HEARTS como o modelo para a gestão do risco de doenças cardiovasculares, incluindo hipertensão e diabetes, na atenção primária à saúde nas Américas até 2025. Essa iniciativa está entrando em seu sexto ano de implementação e agora inclui 22 países e 1 380 centros de atenção primária à saúde. Os objetivos deste relatório são três. Primeiramente, ele descreve o surgimento e os principais elementos da Iniciativa HEARTS nas Américas. Em segundo lugar, resume as principais inovações desenvolvidas para catalisar e sustentar a implementação da iniciativa. Essas inovações incluem: a) introdução de fatores impulsionadores de controle da hipertensão; b) desenvolvimento de um caminho clínico abrangente e prático; c) desenvolvimento de uma estratégia para melhorar a exatidão da aferição da pressão arterial; d) criação de uma plataforma de monitoramento e avaliação; e e) desenvolvimento de um conjunto padronizado de recursos para treinamento e educação. Em terceiro lugar, este relatório discute as futuras prioridades da iniciativa. O objetivo de implementar essas soluções inovadoras e pragmáticas é criar um sistema de saúde mais eficaz e mudar o foco dos programas cardiovasculares e de hipertensão do nível de atendimento altamente especializado para a atenção primária à saúde. Além disso, a Iniciativa HEARTS nas Américas pode servir de modelo para práticas mais abrangentes, efetivas e susten- táveis de prevenção e tratamento de doenças não transmissíveis.

Mechanistic Analysis of an Extracellular Signal-Regulated Kinase 2-Interacting Compound that Inhibits Mutant BRAF-Expressing Melanoma Cells by Inducing Oxidative Stress.

Constitutively active extracellular signal-regulated kinase (ERK) 1/2 signaling promotes cancer cell proliferation and survival. We previously described a class of compounds containing a 1,1-dioxido-2,5-dihydrothiophen-3-yl 4-benzenesulfonate scaffold that targeted ERK2 substrate docking sites and selectively inhibited ERK1/2-dependent functions, including activator protein-1-mediated transcription and growth of cancer cells containing active ERK1/2 due to mutations in Ras G-proteins or BRAF, Proto-oncogene B-RAF (Rapidly Acclerated Fibrosarcoma) kinase. The current study identified chemical features required for biologic activity and global effects on gene and protein levels in A375 melanoma cells containing mutant BRAF (V600E). Saturation transfer difference-NMR and mass spectrometry analyses revealed interactions between a lead compound (SF-3-030) and ERK2, including the formation of a covalent adduct on cysteine 252 that is located near the docking site for ERK/FXF (DEF) motif for substrate recruitment. Cells treated with SF-3-030 showed rapid changes in immediate early gene levels, including DEF motif-containing ERK1/2 substrates in the Fos family. Analysis of transcriptome and proteome changes showed that the SF-3-030 effects overlapped with ATP-competitive or catalytic site inhibitors of MAPK/ERK Kinase 1/2 (MEK1/2) or ERK1/2. Like other ERK1/2 pathway inhibitors, SF-3-030 induced reactive oxygen species (ROS) and genes associated with oxidative stress, including nuclear factor erythroid 2-related factor 2 (NRF2). Whereas the addition of the ROS inhibitor N-acetyl cysteine reversed SF-3-030-induced ROS and inhibition of A375 cell proliferation, the addition of NRF2 inhibitors has little effect on cell proliferation. These studies provide mechanistic information on a novel chemical scaffold that selectively regulates ERK1/2-targeted transcription factors and inhibits the proliferation of A375 melanoma cells through a ROS-dependent mechanism. SIGNIFICANCE STATEMENT: Constitutive activation of the extracellular signal-regulated kinase (ERK1/2) pathway drives the proliferation and survival of many cancer cell types. Given the diversity of cellular functions regulated by ERK1/2, the current studies have examined the mechanism of a novel chemical scaffold that targets ERK2 near a substrate binding site and inhibits select ERK functions. Using transcriptomic and proteomic analyses, we provide a mechanistic basis for how this class of compounds inhibits melanoma cells containing mutated BRAF and active ERK1/2.

Cortactin Expression in Hematopoietic Cells: Implications for Hematological Malignancies.

Cortactin is an actin-binding protein expressed in virtually all cell types. It regulates several cell functions, including adhesion and migration. Cortactin overexpression is associated with increased metastasis formation and worse outcome in different types of solid tumors, thus highlighting a critical role of cortactin in cancer progression. Mechanistically, this is due to increased invadopodia formation and matrix metalloproteinase secretion. Cortactin has been until recently considered absent in hematopoietic cells because these cells express the cortactin homolog hematopoietic cell-specific lyn substrate-1. However, many recent reports describe functional expression of cortactin in different hematopoietic cells, such as macrophages, dendritic cells, and lymphocytes. Of note, cortactin is strongly overexpressed in leukemic cell lines and primary patient-derived leukemic cells. In B-cell chronic lymphocytic leukemia, this is associated with poor prognosis and increased chemotaxis; in B-cell acute lymphoblastic leukemia, high cortactin levels correlate with treatment failure and relapse. Moreover, cortactin has been proposed as a diagnostic marker for non-Hodgkin B-cell lymphomas. This review summarizes current knowledge on cortactin expression in hematopoietic cells and discusses the functional implications for different hematological malignancies.

Life expectancy, healthy life expectancy, and burden of disease in older people in the Americas, 1990-2019: a population-based study.

OBJECTIVE: To describe the life expectancy, healthy life expectancy, disease burden, and leading causes of mortality and disability in adults aged 65 years and older in the Region of the Americas from 1990 to 2019. METHODS: We used estimates from the Global Burden of Disease Study 2019 to examine the level and trends of life expectancy, healthy life expectancy, years of life lost, years lived with disability, and disability-adjusted life years (DALYs). RESULTS: Across the Region, life expectancy at 65 years increased from 17.1 years (95% uncertainty intervals (UI): 17.0-17.1) in 1990 to 19.2 years (95% UI: 18.9-19.4) in 2019 while healthy life expectancy increased from 12.2 years (95% UI: 10.9-12.4) to 13.6 years (95% UI: 12.2-14.9). All-cause DALY rates decreased in each older persons' age group; however, absolute proportional DALYs increased from 22% to 32%. Ischemic heart disease, stroke, and chronic obstructive pulmonary disease were the leading causes of premature mortality. Diabetes mellitus, age-related and other hearing loss, and lower back pain were the leading causes of disability. CONCLUSION: The increase in life expectancy and decrease of DALYs indicate the positive effect of improvements in social conditions and health policies. However, the smaller increase in healthy life expectancy suggests that, despite living longer, people spend a substantial amount of time in their old age with disability and illness. Preventable and controllable diseases account for most of the disease burden in older adults in the Americas. Society-wide and life-course approaches, and adequate health services are needed to respond to the health needs of older people in the Region.

Photoredox Organic Synthesis Employing Heterogeneous Photocatalysts with Emphasis on Halide Perovskite.

Lately, heterogeneous semiconductor materials have been explored as an emerging type of efficient photocatalyst for photoredox organic synthesis. Among these semiconductors, lead halide perovskite materials demonstrate unique properties towards excellent charge separation and charge transfer, extremely long charge carrier migration, high efficiency in visible light absorption, and long excited states lifetimes, etc., as proved in ground-breaking solar cell applications, garnering necessary merits for an efficient catalytic system for photoredox organic reactions. Here, the latest progress in heterogeneous semiconductor materials towards this endeavor is examined, with particular emphasis on lead halide perovskite nanocrystals (NCs) in photocatalytic organic synthesis.

Sound Levels Forecasting in an Acoustic Sensor Network Using a Deep Neural Network.

Wireless acoustic sensor networks are nowadays an essential tool for noise pollution monitoring and managing in cities. The increased computing capacity of the nodes that create the network is allowing the addition of processing algorithms and artificial intelligence that provide more information about the sound sources and environment, e.g., detect sound events or calculate loudness. Several models to predict sound pressure levels in cities are available, mainly road, railway and aerial traffic noise. However, these models are mostly based in auxiliary data, e.g., vehicles flow or street geometry, and predict equivalent levels for a temporal long-term. Therefore, forecasting of temporal short-term sound levels could be a helpful tool for urban planners and managers. In this work, a Long Short-Term Memory (LSTM) deep neural network technique is proposed to model temporal behavior of sound levels at a certain location, both sound pressure level and loudness level, in order to predict near-time future values. The proposed technique can be trained for and integrated in every node of a sensor network to provide novel functionalities, e.g., a method of early warning against noise pollution and of backup in case of node or network malfunction. To validate this approach, one-minute period equivalent sound levels, captured in a two-month measurement campaign by a node of a deployed network of acoustic sensors, have been used to train it and to obtain different forecasting models. Assessments of the developed LSTM models and Auto regressive integrated moving average models were performed to predict sound levels for several time periods, from 1 to 60 min. Comparison of the results show that the LSTM models outperform the statistics-based models. In general, the LSTM models achieve a prediction of values with a mean square error less than 4.3 dB for sound pressure level and less than 2 phons for loudness. Moreover, the goodness of fit of the LSTM models and the behavior pattern of the data in terms of prediction of sound levels are satisfactory.

Novel Noncatalytic Substrate-Selective p38α-Specific MAPK Inhibitors with Endothelial-Stabilizing and Anti-Inflammatory Activity.

The p38 MAPK family is composed of four kinases of which p38α/MAPK14 is the major proinflammatory member. These kinases contribute to many inflammatory diseases, but the currently available p38 catalytic inhibitors (e.g., SB203580) are poorly effective and cause toxicity. We reasoned that the failure of catalytic p38 inhibitors may derive from their activity against noninflammatory p38 isoforms (e.g., p38ß/MAPK11) and loss of all p38α-dependent responses, including anti-inflammatory, counterregulatory responses via mitogen- and stress-activated kinase (MSK) 1/2 and Smad3. We used computer-aided drug design to target small molecules to a pocket near the p38α glutamate-aspartate (ED) substrate-docking site rather than the catalytic site, the sequence of which had only modest homology among p38 isoforms. We identified a lead compound, UM101, that was at least as effective as SB203580 in stabilizing endothelial barrier function, reducing inflammation, and mitigating LPS-induced mouse lung injury. Differential scanning fluorimetry and saturation transfer difference-nuclear magnetic resonance demonstrated specific binding of UM101 to the computer-aided drug design-targeted pockets in p38α but not p38ß. RNA sequencing analysis of TNF-α-stimulated gene expression revealed that UM101 inhibited only 28 of 61 SB203580-inhibited genes and 7 of 15 SB203580-inhibited transcription factors, but spared the anti-inflammatory MSK1/2 pathway. We provide proof of principle that small molecules that target the ED substrate-docking site may exert anti-inflammatory effects similar to the catalytic p38 inhibitors, but their isoform specificity and substrate selectivity may confer inherent advantages over catalytic inhibitors for treating inflammatory diseases.