Genome-wide association analyses of breast cancer in women of African ancestry identify new susceptibility loci and improve risk prediction.

We performed genome-wide association studies of breast cancer including 18,034 cases and 22,104 controls of African ancestry. Genetic variants at 12 loci were associated with breast cancer risk (P < 5 × 10-8), including associations of a low-frequency missense variant rs61751053 in ARHGEF38 with overall breast cancer (odds ratio (OR) = 1.48) and a common variant rs76664032 at chromosome 2q14.2 with triple-negative breast cancer (TNBC) (OR = 1.30). Approximately 15.4% of cases with TNBC carried six risk alleles in three genome-wide association study-identified TNBC risk variants, with an OR of 4.21 (95% confidence interval = 2.66-7.03) compared with those carrying fewer than two risk alleles. A polygenic risk score (PRS) showed an area under the receiver operating characteristic curve of 0.60 for the prediction of breast cancer risk, which outperformed PRS derived using data from females of European ancestry. Our study markedly increases the population diversity in genetic studies for breast cancer and demonstrates the utility of PRS for risk prediction in females of African ancestry.

Using genome and transcriptome data from African-ancestry female participants to identify putative breast cancer susceptibility genes.

African-ancestry (AA) participants are underrepresented in genetics research. Here, we conducted a transcriptome-wide association study (TWAS) in AA female participants to identify putative breast cancer susceptibility genes. We built genetic models to predict levels of gene expression, exon junction, and 3' UTR alternative polyadenylation using genomic and transcriptomic data generated in normal breast tissues from 150 AA participants and then used these models to perform association analyses using genomic data from 18,034 cases and 22,104 controls. At Bonferroni-corrected P < 0.05, we identified six genes associated with breast cancer risk, including four genes not previously reported (CTD-3080P12.3, EN1, LINC01956 and NUP210L). Most of these genes showed a stronger association with risk of estrogen-receptor (ER) negative or triple-negative than ER-positive breast cancer. We also replicated the associations with 29 genes reported in previous TWAS at P < 0.05 (one-sided), providing further support for an association of these genes with breast cancer risk. Our study sheds new light on the genetic basis of breast cancer and highlights the value of conducting research in AA populations.

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.

What is the NCD service capacity and disruptions due to COVID-19? Results from the WHO non-communicable disease country capacity survey in the Americas region.

OBJECTIVE: This article presents the Americas regional results of the WHO non-communicable diseases (NCDs) Country Capacity Survey from 2019 to 2021, on NCD service capacity and disruptions from the COVID-19 pandemic. SETTING: Information on public sector primary care services for NCDs, and related technical inputs from 35 countries in the Americas region are provided. PARTICIPANTS: All Ministry of Health officials managing a national NCD programme, from a WHO Member State in the Americas region, were included throughout this study. Government health officials from countries that are not WHO Member States were excluded. OUTCOME MEASURES: The availability of evidence-based NCD guidelines, essential NCD medicines and basic technologies in primary care, cardiovascular disease risk stratification, cancer screening and palliative care services were measured in 2019, 2020 and 2021. NCD service interruptions, reassignments of NCD staff during the COVID-19 pandemic and mitigation strategies to reduce disruptions for NCD services were measured in 2020 and 2021. RESULTS: More than 50% of countries reported a lack of comprehensive package of NCD guidelines, essential medicines and related service inputs. Extensive disruptions in NCD services resulted from the pandemic, with only 12/35 countries (34%), reporting that outpatient NCD services were functioning normally. Ministry of Health staff were largely redirected to work on the COVID-19 response, either full time or partially, reducing the human resources available for NCD services. Six of 24 countries (25%) reported stock out of essential NCD medicines and/or diagnostics at health facilities which affected service continuity. Mitigation strategies to ensure continuity of care for people with NCDs were deployed in many countries and included triaging patients, telemedicine and teleconsultations, and electronic prescriptions and other novel prescribing practices. CONCLUSIONS: The findings from this regional survey suggest significant and sustained disruptions, affecting all countries regardless of the country's level of investments in healthcare or NCD burden.

Noncommunicable diseases in the Americas: a review of the Pan American Health Organization's 25-year program of work / Enfermedades no transmisibles en la Región de las Américas: revisión del programa de trabajo de la Organización Panamericana de la Salud tras 25 años de actividades / Doenças não transmissíveis nas Américas: uma revisão do programa de trabalho de 25 anos da Organização Pan-Americana da Saúde

ABSTRACT 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.

RESUMEN 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.

RESUMO 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.

Prioritizing noncommunicable diseases in the Americas region in the era of COVID-19.

This article describes the situation of noncommunicable diseases (NCDs) in the Americas, implementation of NCD interventions according to key progress indicators, the impact of COVID-19 on NCD services, and ways to reprioritize NCDs following COVID-19. Information was retrieved from institutional data and through a supplementary scoping review of published articles related to NCDs and COVID-19 in the Americas published April 2020-November 2021. While NCDs account for 80.7% of all deaths in the Americas, implementation of a key set of NCD interventions has been limited, with only three countries reporting implementation of 12 or more of the 19 NCD indicators. By mid-May 2022, the Americas had reported about 29.9% of all COVID-19 cases in the world (154 million of 515 million) and 43.5% all COVID-19 deaths (2.7 million of 6.2 million). This pandemic has hampered progress on NCDs and significantly disrupted services for people who require ongoing care. Adaptive strategies, such as telehealth and mobile pharmacies, have been used to mitigate service disruptions. However, NCD prevention and management must be an integral part of recovering from the COVID-19 pandemic. This will require scaled up efforts to establish/re-establish and enforce policies on NCD risk factors, especially for tobacco control and obesity prevention, as well as greater investment in primary care and expansion of telemedicine and digital health solutions for continuous care for people with NCDs. Lastly, limited data are available on the impact of COVID-19 on NCDs, and hence NCD data and surveillance need to be strengthened.

En este artículo se describe la situación de las enfermedades no transmisibles (ENT) en la Región de las Américas, la ejecución de intervenciones contra las ENT según los indicadores clave de progreso, el efecto de la COVID-19 en los servicios contra las ENT y las formas de priorizar nuevamente las ENT tras la COVID-19. Se obtuvo información de datos institucionales y mediante una revisión exploratoria complementaria de artículos relacionados con las ENT y la COVID-19 en la Región publicados entre abril del 2020 y noviembre del 2021. Si bien las ENT representan 80,7 % de todas las muertes en la Región, la ejecución de un conjunto clave de intervenciones contra las ENT ha sido limitada, y solo tres países han notificado la ejecución de 12 o más indicadores de los 19 indicadores relativos a las ENT. A mediados de mayo del 2022, la Región había notificado alrededor de 29,9 % de todos los casos de COVID-19 en el mundo (154 millones de 515 millones) y 43,5 % del total de muertes por COVID-19 (2,7 millones de 6,2 millones). Esta pandemia ha obstaculizado el progreso contra las ENT y ha causado interrupciones significativas en los servicios para las personas que requieren atención continua. Para mitigar las interrupciones en los servicios se han empleado estrategias de adaptación, como la telemedicina y las farmacias móviles. Sin embargo, la prevención y el manejo de las ENT deben constituir una parte integral de la recuperación de la pandemia de COVID-19. Esto requerirá mayores esfuerzos de establecimiento, restablecimiento y cumplimiento de políticas sobre los factores de riesgo de las ENT, especialmente el control del tabaco y la prevención de la obesidad; así como una mayor inversión en atención primaria y la expansión de la telemedicina y las iniciativas de salud digital para la atención continua de las personas con ENT. Por último, se dispone de datos limitados sobre el impacto de la COVID-19 en las ENT y, por lo tanto, es necesario reforzar la recopilación de datos y la vigilancia de las ENT.

Este artigo descreve a situação das doenças não transmissíveis (DNTs) nas Américas, a implementação de intervenções para DNTs de acordo com indicadores de progresso importantes, o impacto da COVID-19 nos serviços de DNT e formas de priorizar novamente as DNTs após a COVID-19. As informações foram obtidas a partir de dados institucionais e uma revisão de escopo complementar de artigos relacionados a DNTs e COVID-19 nas Américas, publicados entre abril de 2020 e novembro de 2021. Embora as DNTs representem 80,7% de todas as mortes nas Américas, a implementação de um conjunto essencial de intervenções para DNTs tem sido limitada. Apenas três países relataram a implementação de 12 ou mais dos 19 indicadores de DNT. Até meados de maio de 2022, as Américas haviam registrado 29,9% de todos os casos de COVID-19 no mundo (154 milhões de 515 milhões) e 43,5% de todas as mortes por COVID-19 (2,7 milhões de 6,2 milhões). Essa pandemia atrapalhou o avanço com relação às DNTs e prejudicou significativamente a prestação de serviços para pessoas que necessitam de cuidados contínuos. Estratégias adaptativas, como telessaúde e farmácias móveis, foram utilizadas para mitigar as interrupções dos serviços. Porém, a prevenção e o manejo das DNTs devem ser parte integrante da recuperação da pandemia de COVID-19. Isso vai exigir mais esforços para estabelecer/restabelecer e fiscalizar políticas voltadas para fatores de risco para DNTs, principalmente controle do tabagismo e prevenção da obesidade, além de maior investimento na atenção primária e na expansão da telemedicina e de soluções digitais em saúde para cuidados continuados de pessoas com DNTs. Por fim, os dados disponíveis sobre o impacto da COVID-19 nas DNTs são limitados; portanto, é preciso fortalecer os dados e a vigilância de DNTs.

Polygenic risk scores for prediction of breast cancer risk in women of African ancestry: a cross-ancestry approach.

Polygenic risk scores (PRSs) are useful for predicting breast cancer risk, but the prediction accuracy of existing PRSs in women of African ancestry (AA) remains relatively low. We aim to develop optimal PRSs for the prediction of overall and estrogen receptor (ER) subtype-specific breast cancer risk in AA women. The AA dataset comprised 9235 cases and 10 184 controls from four genome-wide association study (GWAS) consortia and a GWAS study in Ghana. We randomly divided samples into training and validation sets. We built PRSs using individual-level AA data by a forward stepwise logistic regression and then developed joint PRSs that combined (1) the PRSs built in the AA training dataset and (2) a 313-variant PRS previously developed in women of European ancestry. PRSs were evaluated in the AA validation set. For overall breast cancer, the odds ratio per standard deviation of the joint PRS in the validation set was 1.34 [95% confidence interval (CI): 1.27-1.42] with the area under receiver operating characteristic curve (AUC) of 0.581. Compared with women with average risk (40th-60th PRS percentile), women in the top decile of the PRS had a 1.98-fold increased risk (95% CI: 1.63-2.39). For PRSs of ER-positive and ER-negative breast cancer, the AUCs were 0.608 and 0.576, respectively. Compared with existing methods, the proposed joint PRSs can improve prediction of breast cancer risk in AA women.

Prioritizing noncommunicable diseases in the Americas region in the era of COVID-19 / Priorizar las enfermedades no transmisibles en la Región de las Américas en la era de la COVID-19 / Priorização de doenças não transmissíveis na Região das Américas na era da COVID-19

ABSTRACT This article describes the situation of noncommunicable diseases (NCDs) in the Americas, implementation of NCD interventions according to key progress indicators, the impact of COVID-19 on NCD services, and ways to reprioritize NCDs following COVID-19. Information was retrieved from institutional data and through a supplementary scoping review of published articles related to NCDs and COVID-19 in the Americas published April 2020-November 2021. While NCDs account for 80.7% of all deaths in the Americas, implementation of a key set of NCD interventions has been limited, with only three countries reporting implementation of 12 or more of the 19 NCD indicators. By mid-May 2022, the Americas had reported about 29.9% of all COVID-19 cases in the world (154 million of 515 million) and 43.5% all COVID-19 deaths (2.7 million of 6.2 million). This pandemic has hampered progress on NCDs and significantly disrupted services for people who require ongoing care. Adaptive strategies, such as telehealth and mobile pharmacies, have been used to mitigate service disruptions. However, NCD prevention and management must be an integral part of recovering from the COVID-19 pandemic. This will require scaled up efforts to establish/re-establish and enforce policies on NCD risk factors, especially for tobacco control and obesity prevention, as well as greater investment in primary care and expansion of telemedicine and digital health solutions for continuous care for people with NCDs. Lastly, limited data are available on the impact of COVID-19 on NCDs, and hence NCD data and surveillance need to be strengthened.

RESUMEN En este artículo se describe la situación de las enfermedades no transmisibles (ENT) en la Región de las Américas, la ejecución de intervenciones contra las ENT según los indicadores clave de progreso, el efecto de la COVID-19 en los servicios contra las ENT y las formas de priorizar nuevamente las ENT tras la COVID-19. Se obtuvo información de datos institucionales y mediante una revisión exploratoria complementaria de artículos relacionados con las ENT y la COVID-19 en la Región publicados entre abril del 2020 y noviembre del 2021. Si bien las ENT representan 80,7 % de todas las muertes en la Región, la ejecución de un conjunto clave de intervenciones contra las ENT ha sido limitada, y solo tres países han notificado la ejecución de 12 o más indicadores de los 19 indicadores relativos a las ENT. A mediados de mayo del 2022, la Región había notificado alrededor de 29,9 % de todos los casos de COVID-19 en el mundo (154 millones de 515 millones) y 43,5 % del total de muertes por COVID-19 (2,7 millones de 6,2 millones). Esta pandemia ha obstaculizado el progreso contra las ENT y ha causado interrupciones significativas en los servicios para las personas que requieren atención continua. Para mitigar las interrupciones en los servicios se han empleado estrategias de adaptación, como la telemedicina y las farmacias móviles. Sin embargo, la prevención y el manejo de las ENT deben constituir una parte integral de la recuperación de la pandemia de COVID-19. Esto requerirá mayores esfuerzos de establecimiento, restablecimiento y cumplimiento de políticas sobre los factores de riesgo de las ENT, especialmente el control del tabaco y la prevención de la obesidad; así como una mayor inversión en atención primaria y la expansión de la telemedicina y las iniciativas de salud digital para la atención continua de las personas con ENT. Por último, se dispone de datos limitados sobre el impacto de la COVID-19 en las ENT y, por lo tanto, es necesario reforzar la recopilación de datos y la vigilancia de las ENT.

RESUMO Este artigo descreve a situação das doenças não transmissíveis (DNTs) nas Américas, a implementação de intervenções para DNTs de acordo com indicadores de progresso importantes, o impacto da COVID-19 nos serviços de DNT e formas de priorizar novamente as DNTs após a COVID-19. As informações foram obtidas a partir de dados institucionais e uma revisão de escopo complementar de artigos relacionados a DNTs e COVID-19 nas Américas, publicados entre abril de 2020 e novembro de 2021. Embora as DNTs representem 80,7% de todas as mortes nas Américas, a implementação de um conjunto essencial de intervenções para DNTs tem sido limitada. Apenas três países relataram a implementação de 12 ou mais dos 19 indicadores de DNT. Até meados de maio de 2022, as Américas haviam registrado 29,9% de todos os casos de COVID-19 no mundo (154 milhões de 515 milhões) e 43,5% de todas as mortes por COVID-19 (2,7 milhões de 6,2 milhões). Essa pandemia atrapalhou o avanço com relação às DNTs e prejudicou significativamente a prestação de serviços para pessoas que necessitam de cuidados contínuos. Estratégias adaptativas, como telessaúde e farmácias móveis, foram utilizadas para mitigar as interrupções dos serviços. Porém, a prevenção e o manejo das DNTs devem ser parte integrante da recuperação da pandemia de COVID-19. Isso vai exigir mais esforços para estabelecer/restabelecer e fiscalizar políticas voltadas para fatores de risco para DNTs, principalmente controle do tabagismo e prevenção da obesidade, além de maior investimento na atenção primária e na expansão da telemedicina e de soluções digitais em saúde para cuidados continuados de pessoas com DNTs. Por fim, os dados disponíveis sobre o impacto da COVID-19 nas DNTs são limitados; portanto, é preciso fortalecer os dados e a vigilância de DNTs.

Integrated approach for noncommunicable disease management in the Americas / Un enfoque integrado para el manejo de las enfermedades no transmisibles en la Región de las Américas / Uma abordagem integrada para o manejo das doenças não transmissíveis nas Américas

ABSTRACT An overview of an integrated approach to improve noncommunicable disease (NCD) management is presented, along with tools on integrating NCD management as part of health system strengthening in the Americas. The study is based on an analysis of Pan American Health Organization/World Health Organization (PAHO/WHO) data and publicly available information on NCD care and capacity, disruptions in NCD services, and guidance on NCD management. Gaps in NCD care are highlighted, in which an estimated 43.0% of men and 28.0% of women with hypertension in Latin America remain undiagnosed; and for those with diabetes, 32.8% in Central and South America are undiagnosed. Yet, only 17/35 countries (49%) in the Americas report having evidence-based national guidelines for NCD management through a primary care approach and only 7/35 countries (20%) report provision of drug therapy, including glycaemic control for eligible persons. To improve NCD management, an integrated approach is needed to coordinate and deliver care across the levels of the health system. This includes increasing primary care capacity and competencies to address multiple chronic conditions, and integration with other complementary programs to avoid missing opportunities for NCD diagnosis and management. An integrated approach to NCD management, and implementation of available tools, should be part of rebuilding health systems after the COVID-19 pandemic.

RESUMEN En este artículo se presenta una visión general de un enfoque integrado para mejorar el manejo de las enfermedades no transmisibles (ENT), así como herramientas para integrar el manejo de las ENT como parte del fortalecimiento de los sistemas de salud en la Región de las Américas. El estudio se basa en un análisis de datos de la Organización Panamericana de la Salud/Organización Mundial de la Salud (OPS/OMS) y en información disponible para el público sobre la atención de las ENT y la capacidad, las interrupciones en los servicios y la orientación sobre el manejo de las ENT. Se destacan las brechas en la atención de estas enfermedades; se estima que 43,0% de los hombres y 28,0% de las mujeres con hipertensión en América Latina siguen sin recibir un diagnóstico, mientras que entre las personas con diabetes, 32,8% en América Central y del Sur no están diagnosticadas. Sin embargo, únicamente 17 de 35 países de la Región (49%) afirman disponer de pautas nacionales basadas en la evidencia para el manejo de las ENT mediante un enfoque de atención primaria, y solo 7 de 35 países (20%) refieren la provisión de farmacoterapia —por ejemplo, para el control glucémico— para las personas que reúnen los requisitos. Para mejorar el manejo de las ENT, es necesario un enfoque integrado para coordinar y brindar atención en todos los niveles del sistema de salud. Esto supone el aumento de la capacidad y las competencias de la atención primaria para abordar diversas enfermedades crónicas y su integración con otros programas complementarios y así no perder oportunidades de diagnosticar y gestionar las ENT. Un enfoque integrado para el manejo de las ENT y la aplicación de las herramientas disponibles deben formar parte de la reconstrucción de los sistemas de salud después de la pandemia de COVID-19.

RESUMO O documento apresenta uma visão geral de uma abordagem integrada para melhorar o manejo de doenças não transmissíveis (DNT), bem com ferramentas para posicionar o manejo das DNT como parte integrante do fortalecimento dos sistemas de saúde nas Américas. O estudo tem como base uma análise dos dados da Organização Pan-Americana da Saúde/Organização Mundial da Saúde (OPAS/OMS) e informações disponíveis publicamente sobre cuidados e capacidade de atendimento a DNT, interrupções nos serviços de DNT e orientações sobre o manejo de DNT. São destacadas as lacunas na atenção às DNT. Estima-se que 43,0% dos homens e 28,0% das mulheres com hipertensão na América Latina permanecem sem diagnóstico, e entre aqueles com diabetes, 32,8% na América Central e do Sul permanecem sem diagnóstico. Apenas 17 de 35 países (49%) nas Américas relatam ter diretrizes nacionais baseadas em evidências para o manejo de DNT na atenção primária e apenas 7 de 35 países (20%) relatam o fornecimento de terapia medicamentosa, incluindo medicamentos para o controle glicêmico para pessoas elegíveis. Para melhorar o manejo das DNT, é necessária uma abordagem integrada para coordenar e prestar cuidados em todos os níveis do sistema de saúde. Isso inclui o aumento da capacidade e da competência da atenção primária para atender pessoas com múltiplas doenças crônicas e a integração com outros programas complementares para evitar a perda de oportunidades para o diagnóstico e o manejo das DNT. Uma abordagem integrada ao manejo das DNT e a implementação das ferramentas disponíveis devem fazer parte da reconstrução dos sistemas de saúde após a pandemia de COVID-19.

Cross-ancestry GWAS meta-analysis identifies six breast cancer loci in African and European ancestry women.

Our study describes breast cancer risk loci using a cross-ancestry GWAS approach. We first identify variants that are associated with breast cancer at P < 0.05 from African ancestry GWAS meta-analysis (9241 cases and 10193 controls), then meta-analyze with European ancestry GWAS data (122977 cases and 105974 controls) from the Breast Cancer Association Consortium. The approach identifies four loci for overall breast cancer risk [1p13.3, 5q31.1, 15q24 (two independent signals), and 15q26.3] and two loci for estrogen receptor-negative disease (1q41 and 7q11.23) at genome-wide significance. Four of the index single nucleotide polymorphisms (SNPs) lie within introns of genes (KCNK2, C5orf56, SCAMP2, and SIN3A) and the other index SNPs are located close to GSTM4, AMPD2, CASTOR2, and RP11-168G16.2. Here we present risk loci with consistent direction of associations in African and European descendants. The study suggests that replication across multiple ancestry populations can help improve the understanding of breast cancer genetics and identify causal variants.

Evaluating Polygenic Risk Scores for Breast Cancer in Women of African Ancestry.

BACKGROUND: Polygenic risk scores (PRSs) have been demonstrated to identify women of European, Asian, and Latino ancestry at elevated risk of developing breast cancer (BC). We evaluated the performance of existing PRSs trained in European ancestry populations among women of African ancestry. METHODS: We assembled genotype data for women of African ancestry, including 9241 case subjects and 10 193 control subjects. We evaluated associations of 179- and 313-variant PRSs with overall and subtype-specific BC risk. PRS discriminatory accuracy was assessed using area under the receiver operating characteristic curve. We also evaluated a recalibrated PRS, replacing the index variant with variants in each region that better captured risk in women of African ancestry and estimated lifetime absolute risk of BC in African Americans by PRS category. RESULTS: For overall BC, the odds ratio per SD of the 313-variant PRS (PRS313) was 1.27 (95% confidence interval [CI] = 1.23 to 1.31), with an area under the receiver operating characteristic curve of 0.571 (95% CI = 0.562 to 0.579). Compared with women with average risk (40th-60th PRS percentile), women in the top decile of PRS313 had a 1.54-fold increased risk (95% CI = 1.38-fold to 1.72-fold). By age 85 years, the absolute risk of overall BC was 19.6% for African American women in the top 1% of PRS313 and 6.7% for those in the lowest 1%. The recalibrated PRS did not improve BC risk prediction. CONCLUSION: The PRSs stratify BC risk in women of African ancestry, with attenuated performance compared with that reported in European, Asian, and Latina populations. Future work is needed to improve BC risk stratification for women of African ancestry.

A meta-analysis of genome-wide association studies of multiple myeloma among men and women of African ancestry.

Persons of African ancestry (AA) have a twofold higher risk for multiple myeloma (MM) compared with persons of European ancestry (EA). Genome-wide association studies (GWASs) support a genetic contribution to MM etiology in individuals of EA. Little is known about genetic risk factors for MM in individuals of AA. We performed a meta-analysis of 2 GWASs of MM in 1813 cases and 8871 controls and conducted an admixture mapping scan to identify risk alleles. We fine-mapped the 23 known susceptibility loci to find markers that could better capture MM risk in individuals of AA and constructed a polygenic risk score (PRS) to assess the aggregated effect of known MM risk alleles. In GWAS meta-analysis, we identified 2 suggestive novel loci located at 9p24.3 and 9p13.1 at P < 1 × 10-6; however, no genome-wide significant association was noted. In admixture mapping, we observed a genome-wide significant inverse association between local AA at 2p24.1-23.1 and MM risk in AA individuals. Of the 23 known EA risk variants, 20 showed directional consistency, and 9 replicated at P < .05 in AA individuals. In 8 regions, we identified markers that better capture MM risk in persons with AA. AA individuals with a PRS in the top 10% had a 1.82-fold (95% confidence interval, 1.56-2.11) increased MM risk compared with those with average risk (25%-75%). The strongest functional association was between the risk allele for variant rs56219066 at 5q15 and lower ELL2 expression (P = 5.1 × 10-12). Our study shows that common genetic variation contributes to MM risk in individuals with AA.

Commentary: setting priorities in NCD prevention and control.

Decision making in health requires the use of sound evidence and context-specific information, guided by a priority setting methodology or framework. For noncommunicable disease (NCD) prevention and control, a decision-making methodology has been applied by the World Health Organization to delineate priorities, and options for cost-effective NCD interventions. A set of 14 interventions considered very cost-effective, affordable and feasible for implementation in various resource level settings were identified. Among them, tobacco control through taxation, bans on tobacco advertising, plain packaging, and smoke free public spaces stands out as perhaps the single most important interventions to tackle NCDs.

Genetic variants demonstrating flip-flop phenomenon and breast cancer risk prediction among women of African ancestry.

BACKGROUND: Few studies have evaluated the performance of existing breast cancer risk prediction models among women of African ancestry. In replication studies of genetic variants, a change in direction of the risk association is a common phenomenon. Termed flip-flop, it means that a variant is risk factor in one population but protective in another, affecting the performance of risk prediction models. METHODS: We used data from the genome-wide association study (GWAS) of breast cancer in the African diaspora (The Root consortium), which included 3686 participants of African ancestry from Nigeria, USA, and Barbados. Polygenic risk scores (PRSs) were constructed from the published odds ratios (ORs) of four sets of susceptibility loci for breast cancer. Discrimination capacity was measured using the area under the receiver operating characteristic curve (AUC). RESULTS: Flip-flop phenomenon was observed among 30~40% of variants across studies. Using the 34 variants with consistent directionality among previous studies, we constructed a PRS with AUC of 0.531 (95% confidence interval [CI]: 0.512-0.550), which is similar to the PRS using 93 variants and ORs from European ancestry populations (AUC = 0.525, 95% CI: 0.506-0.544). Additionally, we found the 34-variant PRS has good discriminative accuracy in women with family history of breast cancer (AUC = 0.586, 95% CI: 0.532-0.640). CONCLUSIONS: We found that PRS based on variants identified from prior GWASs conducted in women of European and Asian ancestries did not provide a comparable degree of risk stratification for women of African ancestry. Further large-scale fine-mapping studies in African ancestry populations are desirable to discover population-specific genetic risk variants.

Prevalence and phenotype of diabetes and prediabetes using fasting glucose vs HbA1c in a Caribbean population.

BACKGROUND: Both fasting plasma glucose (FPG) and HbA1c are recommended for the diagnosis of diabetes and prediabetes by the American Diabetes Association (ADA), and for diabetes by the World Health Organization. The ADA guidance is influential on clinical practice in many developing countries, including in the Caribbean and Latin America. We aimed to compare the prevalence and characteristics of individuals identified as having diabetes and prediabetes by FPG and HbA1c in a predominantly African ancestry Caribbean population. METHODS: A representative population-based sample of 1234 adults (≥25 years of age) resident in Barbados was recruited. Standard methods with appropriate quality control were used to collect data on height, weight, blood pressure, fasting lipids and history of diagnosed diabetes, and to measure fasting glucose and HbA1c. Those with previously diagnosed diabetes (n = 192) were excluded from the analyses. Diabetes was defined as: FPG ≥7.0 mmol/L or HbA1c ≥6.5%; prediabetes as: FPG ≥5.6 to <7mmol/L or HbA1c ≥5.7 to <6.5%. RESULTS: Complete data were available on 939 participants without previously diagnosed diabetes. The prevalence of undiagnosed diabetes was higher, but not significantly so, by HbA1c (4.9%, 95% CI 3.5, 6.8) vs FPG (3.5%, 2.4, 5.1). Overall 79 individuals had diabetes by either measure, but only 21 on both. The prevalence of prediabetes was higher by HbA1c compared to FPG: 41.7% (37.9, 45.6) vs 15.0% (12.8, 17.5). Overall 558 individuals had prediabetes by either measure, but only 107 on both. HbA1c, but not FPG, was significantly higher in women than men; and FPG, but not HbA1c, was significantly associated with raised triglycerides and low HDL cholesterol. CONCLUSION: The agreement between FPG and HbA1c defined hyperglycaemia is poor. In addition, there are some differences in the phenotype of those identified, and HbA1c gives a much higher prevalence of prediabetes. The routine use of HbA1c for screening and diagnosis in this population would have major implications for clinical and public health policies and resources. Given the lack of robust evidence, particularly for prediabetes, on whether intervention in the individuals identified would improve outcomes, this approach to screening and diagnosis cannot be currently recommended for this population.

Monitoring Caribbean tobacco use: baseline adolescent smoking prevalence and regional disparities.

OBJECTIVE:: To provide baseline information on tobacco use among adolescents in the Caribbean for the period before country-level implementation of the Framework Convention on Tobacco Control (WHO-FCTC). MATERIALS AND METHODS:: Using Global Youth Tobacco Surveys (GYTS) between 2000 and 2008, we report baseline prevalence, 5-year change, and disparities in tobacco use (ever smoked, currently smoke) among adolescents. RESULTS:: The Caribbean prevalence of ever-smoked fell from 33.3 to 29.0% with nine of 14 countries reporting a 5-year decrease, and the prevalence of current smokers fell from 12.1 to 11.7% with eight of 14 countries reporting a 5-year decrease. Between-country disparities in the prevalence of ever smoked decreased, while between-country disparities in currently smoked saw little change. CONCLUSIONS:: This regional summary of tobacco use provides baseline estimates of adolescent smoking, and cross-country smoking disparities for the period before MPOWER implementation. Subsequent GYTS survey rounds can be used to monitor program success.

Characterizing Genetic Susceptibility to Breast Cancer in Women of African Ancestry.

Background: Genome-wide association studies have identified approximately 100 common genetic variants associated with breast cancer risk, the majority of which were discovered in women of European ancestry. Because of different patterns of linkage disequilibrium, many of these genetic markers may not represent signals in populations of African ancestry.Methods: We tested 74 breast cancer risk variants and conducted fine-mapping of these susceptibility regions in 6,522 breast cancer cases and 7,643 controls of African ancestry from three genetic consortia (AABC, AMBER, and ROOT).Results: Fifty-four of the 74 variants (73%) were found to have ORs that were directionally consistent with those previously reported, of which 12 were nominally statistically significant (P < 0.05). Through fine-mapping, in six regions (3p24, 12p11, 14q13, 16q12/FTO, 16q23, 19p13), we observed seven markers that better represent the underlying risk variant for overall breast cancer or breast cancer subtypes, whereas in another two regions (11q13, 16q12/TOX3), we identified suggestive evidence of signals that are independent of the reported index variant. Overlapping chromatin features and regulatory elements suggest that many of the risk alleles lie in regions with biological functionality.Conclusions: Through fine-mapping of known susceptibility regions, we have revealed alleles that better characterize breast cancer risk in women of African ancestry.Impact: The risk alleles identified represent genetic markers for modeling and stratifying breast cancer risk in women of African ancestry. Cancer Epidemiol Biomarkers Prev; 26(7); 1016-26. ©2017 AACR.