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.

Multimorbidity and social determinants of health in the US prior to the COVID-19 pandemic and implications for health outcomes: a cross-sectional analysis based on NHANES 2017-2018.

Multimorbidity increases the risk of all-cause mortality, and along with age, is an independent risk factor for severe disease and mortality from COVID-19. Inequities in the social determinants of health contributed to increased mortality from COVID-19 among disadvantaged populations. This study aimed to evaluate the prevalence of multimorbid conditions and associations with the social determinants of health in the US prior to the pandemic.Methods Data from the 2017-18 cycle of NHANES were used to determine the prevalence of 13 chronic conditions, and the prevalence of having 0, 1, or 2 or more of those conditions, among the US adult population aged ≥ 20 years. Multimorbidity was defined as having 2 or more of these conditions. Data were stratified according to demographic, socioeconomic and indicators of health access, and analyses including logistic regression, performed to determine the factors associated with multimorbidity.Results The prevalence of multimorbidity was 58.4% (95% CI 55.2 to 61.7). Multimorbidity was strongly associated with age and was highly prevalent among those aged 20-29 years at 22.2% (95% CI 16.9 to 27.6) and continued to increase with older age. The prevalence of multimorbidity was highest in those defined as Other or multiple races (66.9%), followed in decreasing frequency by rates among non-Hispanic Whites (61.2%), non-Hispanic Blacks (57.4%), Hispanic (52.0%) and Asian (41.3%) groups.Logistic regression showed a statistically significant relationship between multimorbidity and age, as expected. Asian race was associated with a reduced likelihood of 2 or more chronic conditions (OR 0.4; 95% CI 0.35 to 0.57; P < 0.0001). Socioeconomic factors were related to multimorbidity. Being above the poverty level (OR 0.64; 95% CI 0.46 to 0.91, p = 0.013); and a lack of regular access to health care (OR 0.61 (95% CI 0.42 to 0.88, p = 0.008) were both associated with a reduced likelihood of multimorbidity. Furthermore, there was a borderline association between not having health insurance and reduced likelihood of multimorbidity (OR 0.63; 95% CI 0.40 to 1.0; p = 0.053).Conclusions There are high levels of multimorbidity in the US adult population, evident from young adulthood and increasing with age. Cardiometabolic causes of multimorbidity were highly prevalent, especially obesity, hyperlipidemia, hypertension, and diabetes; conditions subsequently found to be associated with severe disease and death from COVID-19. A lack of access to care was paradoxically associated with reduced likelihood of comorbidity, likely linked to underdiagnosis of chronic conditions. Obesity, poverty, and lack of access to healthcare are factors related to multimorbidity and were also relevant to the health impact of the COVID-19 pandemic, that must be addressed through comprehensive social and public policy measures. More research is needed on the etiology and determinants of multimorbidity, on those affected, patterns of co-morbidity, and implications for individual health and impact on health systems and society to promote optimal outcomes. Comprehensive public health policies are needed to tackle multimorbidity and reduce disparities in the social determinants of health, as well as to provide universal access to healthcare.

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.

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.

Integrated approach for noncommunicable disease management in the Americas.

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.

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.

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.

COVID-19 and inequities in the Americas: lessons learned and implications for essential health services.

The COVID-19 pandemic has exacerbated social, economic, and health-related disparities, which disproportionately affect persons living in conditions of vulnerability. Such populations include ethnic groups who face discrimination and experience barriers to accessing comprehensive health care. The COVID-19 pandemic has exposed these health disparities, and disruptions of essential health services have further widened the gaps in access to health care. Noncommunicable diseases are more prevalent among groups most impacted by poor social determinants of health and have been associated with an increased likelihood of severe COVID-19 disease and higher mortality. Disruptions in the provision of essential health services for noncommunicable diseases, mental health, communicable diseases such as HIV, tuberculosis, and malaria, and maternal and child health services (including sexual and reproductive health), are projected to also increase poor health outcomes. Other challenges have been an increased frequency of interpersonal violence and food insecurity. Countries in the Americas have responded to the disruptions caused by the pandemic by means of health service delivery through telemedicine and other digital solutions and stepping up social service support interventions. As vaccinations for COVID-19 create the opportunity to overcome the pandemic, countries must strengthen primary health care and essential health services with a view to ensuring equity, if the region is to achieve universal health coverage in fulfillment of the Sustainable Development Goals.

La pandemia de COVID-19 ha acentuado las desigualdades sociales, económicas y relacionadas con la salud, que afectan desproporcionadamente a las personas en situación de vulnerabilidad. Esta población incluye grupos étnicos que se enfrentan a la discriminación y obstáculos para el acceso a la atención integral de salud. La pandemia de COVID-19 ha expuesto estas desigualdades de salud, y las interrupciones de los servicios esenciales de salud han ampliado aún más las brechas en el acceso a la atención de salud. Las enfermedades no transmisibles son más prevalentes en los grupos que han sufrido un mayor impacto de los determinantes sociales de la salud deficientes y se han asociado con una mayor probabilidad de presentar un cuadro grave de COVID-19 y una mayor mortalidad. Asimismo, se proyecta que las interrupciones en la prestación de servicios esenciales de salud para las enfermedades no transmisibles, la salud mental, las enfermedades transmisibles como la infección por el VIH, la tuberculosis y la malaria, y los servicios de salud maternoinfantil (como la salud sexual y reproductiva) incrementen los resultados deficientes en materia de salud. Otros retos son una mayor frecuencia de la violencia interpersonal y la inseguridad alimentaria. Los países de la Región de las Américas han respondido a las interrupciones causadas por la pandemia con la prestación de servicios de salud mediante la telemedicina y otras soluciones digitales, y la aceleración de las intervenciones de apoyo de los servicios sociales. A medida que la vacunación contra la COVID-19 crea la oportunidad de superar la pandemia, los países deben fortalecer su atención primaria de salud y sus servicios de salud esenciales a fin de garantizar la equidad, para que la Región logre la cobertura universal de salud en cumplimiento de los Objetivos de Desarrollo Sostenible.

A pandemia de COVID-19 exacerbou as disparidades sociais, econômicas e as relacionadas à saúde, que afetam de maneira desproporcional as pessoas que vivem em situação de vulnerabilidade. Essas populações incluem grupos étnicos que enfrentam discriminação e barreiras para o acesso à atenção integral à saúde. A pandemia de COVID-19 expôs essas disparidades, e as interrupções nos serviços essenciais de saúde ampliaram ainda mais as lacunas no acesso aos cuidados de saúde. As doenças não transmissíveis são mais prevalentes entre os grupos mais afetados por determinantes sociais da saúde deficientes e estão associadas a um aumento na probabilidade de doença grave pela COVID-19 e mortalidade mais elevada. Prevê-se que as interrupções na prestação de serviços essenciais de saúde para doenças não transmissíveis, saúde mental, doenças transmissíveis como HIV, tuberculose e malária, bem como dos serviços de saúde materno-infantil (incluindo saúde sexual e reprodutiva) também aumentem os desfechos adversos de saúde. Outros desafios são o aumento da frequência da violência interpessoal e insegurança alimentar. Os países das Américas responderam às interrupções causadas pela pandemia com a prestação de serviços de saúde por meio da telemedicina e outras soluções digitais, e a aceleração de intervenções de apoio dos serviços sociais. À medida em que a vacinação contra a COVID-19 oferece a oportunidade de superar a pandemia, os países devem fortalecer a atenção primária à saúde e os serviços essenciais de saúde com o objetivo de garantir a equidade, para que a região atinja a cobertura universal de saúde em cumprimento aos Objetivos de Desenvolvimento Sustentável.

Genome-wide association studies in women of African ancestry identified 3q26.21 as a novel susceptibility locus for oestrogen receptor negative breast cancer.

Multiple breast cancer loci have been identified in previous genome-wide association studies, but they were mainly conducted in populations of European ancestry. Women of African ancestry are more likely to have young-onset and oestrogen receptor (ER) negative breast cancer for reasons that are unknown and understudied. To identify genetic risk factors for breast cancer in women of African descent, we conducted a meta-analysis of two genome-wide association studies of breast cancer; one study consists of 1,657 cases and 2,029 controls genotyped with Illumina's HumanOmni2.5 BeadChip and the other study included 3,016 cases and 2,745 controls genotyped using Illumina Human1M-Duo BeadChip. The top 18,376 single nucleotide polymorphisms (SNP) from the meta-analysis were replicated in the third study that consists of 1,984 African Americans cases and 2,939 controls. We found that SNP rs13074711, 26.5 Kb upstream of TNFSF10 at 3q26.21, was significantly associated with risk of oestrogen receptor (ER)-negative breast cancer (odds ratio [OR]=1.29, 95% CI: 1.18-1.40; P = 1.8 × 10 − 8). Functional annotations suggest that the TNFSF10 gene may be involved in breast cancer aetiology, but further functional experiments are needed. In addition, we confirmed SNP rs10069690 was the best indicator for ER-negative breast cancer at 5p15.33 (OR = 1.30; P = 2.4 × 10 − 10) and identified rs12998806 as the best indicator for ER-positive breast cancer at 2q35 (OR = 1.34; P = 2.2 × 10 − 8) for women of African ancestry. These findings demonstrated additional susceptibility alleles for breast cancer can be revealed in diverse populations and have important public health implications in building race/ethnicity-specific risk prediction model for breast cancer.

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.

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.

Sodium and potassium excretion in an adult Caribbean population of African descent with a high burden of cardiovascular disease.

BACKGROUND: High sodium diets with inadequate potassium and high sodium-to-potassium ratios are a known determinant of hypertension and cardiovascular disease (CVD). The Caribbean island of Barbados has a high prevalence of hypertension and mortality from CVD. Our objectives were to estimate sodium and potassium excretion, to compare estimated levels with recommended intakes and to identify the main food sources of sodium in Barbadian adults. METHODS: A sub-sample (n = 364; 25-64 years) was randomly selected from the representative population-based Health of the Nation cross-sectional study (n = 1234), in 2012-13. A single 24-h urine sample was collected from each participant, following a strictly applied protocol designed to reject incomplete samples, for the measurement of sodium and potassium excretion (in mg), which were used as proxy estimates of dietary intake. In addition, sensitivity analyses based on estimated completeness of urine collection from urine creatinine values were undertaken. Multiple linear regression was used to examine differences in sodium and potassium excretion, and the sodium-to-potassium ratio, by age, sex and educational level. Two 24-h recalls were used to identify the main dietary sources of sodium. All analyses were weighted for the survey design. RESULTS: Mean sodium excretion was 2656 (2488-2824) mg/day, with 67% (62-73%) exceeding the World Health Organization (WHO) recommended limit of 2000 mg/d. Mean potassium excretion was 1469 (1395-1542) mg/d; < 0.5% met recommended minimum intake levels. Mean sodium-to-potassium ratio was 2.0 (1.9-2.1); not one participant had a ratio that met WHO recommendations. Higher potassium intake and lower sodium-to-potassium ratio were independently associated with age and tertiary education. Sensitivity analyses based on urine creatinine values did not notably alter these findings. CONCLUSIONS: In this first nationally representative study with objective assessment of sodium and potassium excretion in a Caribbean population in over 20 years, levels of sodium intake were high, and potassium intake was low. Younger age and lower educational level were associated with the highest sodium-to-potassium ratios. These findings provide baseline values for planning future policy interventions for non-communicable disease prevention.

Managing acute ischaemic stroke in a small island developing state: meeting the guidelines in Barbados.

BACKGROUND: We describe hospital-based management of acute ischaemic stroke patients in 2010-2013 in Barbados, by comparing documented treatment given in the single tertiary public hospital with international guideline recommendations. METHODS: Evidence-based stroke management guidelines were identified through a systematic literature search. Comparisons were made between these guidelines and documented diagnostic practice (all strokes) and prescribed medication (ischaemic stroke only), using a combination of key informant interviews and national stroke registry data for 2010-2013. RESULTS: Several published international guidelines for the acute management of ischaemic stroke recommended patient management in a dedicated stroke unit or nearest hospital specialised in stroke care. Further, patients should receive clinical diagnosis, CT brain scan, specialist evaluation by a multidisciplinary team and, if eligible, thrombolysis with alteplase within 3-3.5 h of symptom onset. Subsequent secondary prophylaxis, with a platelet aggregation inhibitor and a statin was advised. Barbados had no stroke unit or stroke team, and no official protocol for acute stroke management during the study period. Most of the 1735 stroke patients were managed by emergency physicians at presentation; if admitted, they were managed on general medical wards. Most had a CT scan (1646; 94.9%). Of 1406 registered ischaemic stroke patients, only 6 (0.4%) had been thrombolysed, 521 (37.1%) received aspirin within 24 h of admission and 670 (47.7%) were prescribed aspirin on discharge. CONCLUSIONS: Acute ischaemic stroke diagnosis was consistent with international recommendations, although this was less evident for treatment. While acknowledging the difficulty in implementing international guidelines in a low-resource setting, there is scope for improvement in acute ischaemic stroke management and/or its documentation in Barbados. A stroke unit was established in August 2013 and written clinical protocols for acute stroke care were in development at the time of the study; future registry data will evaluate their impact. Our findings have implications for other low-resource settings with high stroke burden.

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.

[Improved Blood Pressure Control to Reduce Cardiovascular Disease Morbidity and Mortality: The Standardized Hypertension Treatment and Prevention Project]. / Mejor control de la presión arterial para reducir la morbilidad y mortalidad por enfermedades cardiovasculares: Proyecto de Prevención y Tratamiento Estandarizado de la Hipertensión Arterial * Traducción oficial al español efectuada por la Organización Panamericana de la Salud a partir del artículo original publicado en el Journal of Clinical Hypertension, con autorización de John Wiley and Sons. En caso de discrepancia prevalecerá la versión original (en inglés).

Hypertension is the leading remediable risk factor for cardiovascular disease, affecting more than 1 billion people worldwide, and is responsible for more than 10 million preventable deaths globally each year. While hypertension can be successfully diagnosed and treated, only one in seven persons with hypertension have controlled blood pressure. To meet the challenge of improving the control of hypertension, particularly in low- and middle-income countries, the authors developed the Standardized Hypertension Treatment and Prevention Project, which involves a health systems-strengthening approach that advocates for standardized hypertension management using evidence-based interventions. These interventions include the use of standardized treatment protocols, a core set of medications along with improved procurement mechanisms to increase the availability and affordability of these medications, registries for cohort monitoring and evaluation, patient empowerment, team-based care (task shifting), and community engagement. With political will and strong partnerships, this approach provides the groundwork to reduce high blood pressure and cardiovascular disease-related morbidity and mortality.

Genetic variants in microRNA and microRNA biogenesis pathway genes and breast cancer risk among women of African ancestry.

MicroRNAs (miRNA) regulate breast biology by binding to specific RNA sequences, leading to RNA degradation and inhibition of translation of their target genes. While germline genetic variations may disrupt some of these interactions between miRNAs and their targets, studies assessing the relationship between genetic variations in the miRNA network and breast cancer risk are still limited, particularly among women of African ancestry. We systematically put together a list of 822 and 10,468 genetic variants among primary miRNA sequences and 38 genes in the miRNA biogenesis pathway, respectively; and examined their association with breast cancer risk in the ROOT consortium which includes women of African ancestry. Findings were replicated in an independent consortium. Logistic regression was used to estimate the odds ratio (OR) and 95 % confidence intervals (CI). For overall breast cancer risk, three single-nucleotide polymorphisms (SNPs) in miRNA biogenesis genes DROSHA rs78393591 (OR = 0.69, 95 % CI: 0.55-0.88, P = 0.003), ESR1 rs523736 (OR = 0.88, 95 % CI: 0.82-0.95, P = 3.99 × 10(-4)), and ZCCHC11 rs114101502 (OR = 1.33, 95 % CI: 1.11-1.59, P = 0.002), and one SNP in primary miRNA sequence (rs116159732 in miR-6826, OR = 0.74, 95 % CI: 0.63-0.89, P = 0.001) were found to have significant associations in both discovery and validation phases. In a subgroup analysis, two SNPs were associated with risk of estrogen receptor (ER)-negative breast cancer, and three SNPs were associated with risk of ER-positive breast cancer. Several variants in miRNA and miRNA biogenesis pathway genes were associated with breast cancer risk. Risk associations varied by ER status, suggesting potential new mechanisms in etiology.

Race and Tobacco Use: A Global Perspective.

These findings suggest that there are no "fixed" racial patterns of tobacco use around the globe. Cross-country differences in tobacco use among races could be modified by cultural influences, domestic tobacco control, or socioeconomic factors. There is need for enhanced efforts to monitor tobacco use by race/ethnicity to identify existing and emerging patterns in tobacco use by race, as well as identify opportunities for interventions. Tailored interventions to reduce tobacco use within different settings and countries may help reduce tobacco use among racial/ethnic minorities. Implementation of comprehensive tobacco control measures could be facilitated by community-based efforts, ensuring that disadvantaged populations are engaged as partners to adapt tobacco control policies and interventions to local contexts and health equity issues.

Establishing national noncommunicable disease surveillance in a developing country: a model for small island nations.

Objective To describe the surveillance model used to develop the first national, population-based, multiple noncommunicable disease (NCD) registry in the Caribbean (one of the first of its kind worldwide); registry implementation; lessons learned; and incidence and mortality rates from the first years of operation. Methods Driven by limited national resources, this initiative of the Barbados Ministry of Health (MoH), in collaboration with The University of the West Indies, was designed to collect prospective data on incident stroke and acute myocardial infarction (MI) (heart attack) cases from all health care facilities in this small island developing state (SIDS) in the Eastern Caribbean. Emphasis is on tertiary and emergency health care data sources. Incident cancer cases are obtained retrospectively, primarily from laboratories. Deaths are collected from the national death register. Results Phased introduction of the Barbados National Registry for Chronic NCDs ("the BNR") began with the stroke component ("BNR-Stroke," 2008), followed by the acute MI component ("BNR-Heart," 2009) and the cancer component ("BNR-Cancer," 2010). Expected case numbers projected from prior studies estimated an average of 378 first-ever stroke, 900 stroke, and 372 acute MI patients annually, and registry data showed an annual average of about 238, 593, and 349 patients respectively. There were 1 204 tumors registered in 2008, versus the expected 1 395. Registry data were used to identify public health training themes. Success required building support from local health care professionals and creating island-wide registry awareness. With spending of approximately US$ 148 per event for 2 200 events per year, the program costs the MoH about US$ 1 per capita annually. Conclusions Given the limited absolute health resources available to SIDS, combined surveillance should be considered for building a national NCD evidence base. With prevalence expected to increase further worldwide, Barbados' experiences are offered as a "road map" for other limited-resource countries considering national NCD surveillance.

Generalizability of established prostate cancer risk variants in men of African ancestry.

Genome-wide association studies have identified more than 80 risk variants for prostate cancer, mainly in European or Asian populations. The generalizability of these variants in other racial/ethnic populations needs to be understood before the loci can be used widely in risk modeling. In our study, we examined 82 previously reported risk variants in 4,853 prostate cancer cases and 4,678 controls of African ancestry. We performed association testing for each variant using logistic regression adjusted for age, study and global ancestry. Of the 82 known risk variants, 68 (83%) had effects that were directionally consistent in their association with prostate cancer risk and 30 (37%) were significantly associated with risk at p < 0.05, with the most statistically significant variants being rs116041037 (p = 3.7 × 10(-26) ) and rs6983561 (p = 1.1 × 10(-16) ) at 8q24, as well as rs7210100 (p = 5.4 × 10(-8) ) at 17q21. By exploring each locus in search of better markers, the number of variants that captured risk in men of African ancestry (p < 0.05) increased from 30 (37%) to 44 (54%). An aggregate score comprised of these 44 markers was strongly associated with prostate cancer risk [per-allele odds ratio (OR) = 1.12, p = 7.3 × 10(-98) ]. In summary, the consistent directions of effects for the vast majority of variants in men of African ancestry indicate common functional alleles that are shared across populations. Further exploration of these susceptibility loci is needed to identify the underlying biologically relevant variants to improve prostate cancer risk modeling in populations of African ancestry.

Cause-of-death disparities in the African diaspora: exploring differences among shared-heritage populations.

OBJECTIVES: We investigated changes in life expectancy (LE) and cause-specific mortality over time, directly comparing African-descent populations in the United States and the Caribbean. METHODS: We compared LE at birth and cause-specific mortality in 6 disease groups between Caribbean countries with a majority (> 90%) African-descent population and US African Americans. RESULTS: The LE improvement among African Americans exceeded that of Afro-Caribbeans so that the LE gap, which favored the Caribbean population by 1.5 years in 1990, had been reversed by 2009. This relative improvement among African Americans was mainly the result of the improving mortality experience of African American men. Between 2000 and 2009, Caribbean mortality rates in 5 of the 6 disease groups increased relative to those of African Americans. By 2009, mortality from cerebrovascular diseases, cancers, and diabetes was higher in Afro-Caribbeans relative to African Americans, with a diabetes mortality rate twice that of African Americans and 4 times that of White Americans. CONCLUSIONS: The Caribbean community made important mortality reductions between 2000 and 2009, but this progress fell short of African American health improvements in the same period, especially among men.

Disparities in hypertension among black Caribbean populations: a scoping review by the U.S. Caribbean Alliance for Health Disparities Research Group (USCAHDR).

BACKGROUND: Despite the large body of research on racial/ethnic disparities in health, there are limited data on health disparities in Caribbean-origin populations. This scoping review aimed to analyze and synthesize published and unpublished literature on the disparities in hypertension and its complications among Afro-Caribbean populations. METHODS: A comprehensive protocol, including a thorough search strategy, was developed and used to identify potentially relevant studies. Identified studies were then screened for eligibility using pre-specified inclusion/exclusion criteria. An extraction form was developed to chart data and collate study characteristics including methods and main findings. Charted information was tagged by disparity indicators and thematic analysis performed. Disparity indicators evaluated include ethnicity, sex, socioeconomic status, disability, sexual orientation and geographic location. Gaps in the literature were identified and extrapolated into a gap map. RESULTS: A total of 455 hypertension related records, published between 1972 and 2012, were identified and screened. Twenty-one studies met inclusion criteria for detailed analysis. The majority of studies were conducted in the United Kingdom and utilized a cross-sectional study design. Overall, studies reported a higher prevalence of hypertension among Caribbean blacks compared to West African blacks and Caucasians. Hypertension and its related complications were highest in persons with low socioeconomic status. Gap analysis showed limited research data reporting hypertension incidence by sex and socioeconomic status. No literature was found on disability status or sexual orientation as it relates to hypertension. Prevalence and morbidity were the most frequently reported outcomes. CONCLUSION: The literature on hypertension health disparities in Caribbean origin populations is limited. Future research should address these knowledge gaps and develop approaches to reduce them.