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.

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.

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.

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.

Disparities in diabetes mellitus among Caribbean populations: a scoping review.

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 review aims to analyze and synthesize published literature on the disparities in diabetes mellitus (DM) and its complications among Afro-Caribbean populations. METHODS: A detailed protocol, including a comprehensive search strategy, was developed and used to identify potentially relevant studies. Identified studies were then screened for eligibility using pre-specified inclusion and 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, age, socioeconomic status, disability and geographic location. Gaps in the literature were identified and extrapolated into a gap map. RESULTS: A total of 1009 diabetes related articles/manuscripts, published between 1972 and 2013, were identified and screened. Forty-three studies met inclusion criteria for detailed analysis. Most studies were conducted in the United Kingdom, Trinidad and Tobago and Jamaica, and used a cross-sectional study design. Overall, studies reported a higher prevalence of DM among Caribbean Blacks compared to West African Blacks and Caucasians but lower when compared to South Asian origin groups. Morbidity from diabetes-related complications was highest in persons with low socioeconomic status. Gap analysis showed limited research data reporting diabetes incidence by sex and socioeconomic status. No published literature was found on disability status or sexual orientation as it relates to diabetes burden or complications. Prevalence and morbidity were the most frequently reported outcomes. CONCLUSION: Literature on diabetes health disparities in Caribbean origin populations is limited. Future research should address these knowledge gaps and develop approaches to reduce them.

Disparities in cardiovascular disease among Caribbean populations: a systematic literature review.

BACKGROUND: Cardiovascular diseases (CVD) are the predominant cause of death globally. The large health disparities in the distribution of the burden of disease seen in developed and developing countries are of growing concern. Central to this concern is the poor outcome which is seen disproportionately in socially disadvantaged groups and racial/ethnic minorities. The aim of the study was to conduct a systematic literature review to investigate the nature of cardiovascular disease health disparities among Afro-Caribbean origin populations and identify current knowledge gaps. METHODS: A systematic literature review including a detailed search strategy was developed to search MEDLINE and other research databases. Using an a priori protocol peer-reviewed publications and grey literature articles were retrieved and screened and relevant data extracted by two independent review authors. Thematic analysis was done according to CVD outcomes and measures of disparity including age, sex, ethnicity and socioeconomic status. RESULTS: The search retrieved 665 articles of which 22 met the inclusion criteria. Most studies were conducted in the United Kingdom and centered on the prevalence of CVD by ethnicity, age and sex. An important sub-theme identified was the disparities in health service utilization/hospital admission. Coronary Heart Disease (CHD) and Peripheral Arterial Disease (PAD) were less prevalent among Afro-Caribbeans compared to Caucasian and South East Asian ethnic groups. The prevalence of CHD ranged from 0-7% in Afro-Caribbean to 2-22% in Caucasians. Strokes were more common among Afro-Caribbeans. There are inadequate data on morbidity and mortality from CVD, particularly across the socio-economic gradient, in Afro-Caribbean populations. CONCLUSIONS: There are important differences in morbidity and mortality from CVD across ethnic groups. Important knowledge gaps remain in understanding the social determinants of these disparities in CVD. More research exploring these gaps by varying disparity indicators needs to be undertaken.

8q24 risk alleles and prostate cancer in African-Barbadian men.

BACKGROUND: African American men (AA) exhibit a disproportionate share of prostate cancer (PRCA) incidence, morbidity, and mortality. Several genetic association studies have implicated select 8q24 loci in PRCA risk in AA. The objective of this investigation is to evaluate the association between previously reported 8q24 risk alleles and PRCA in African-Barbadian (AB) men known to have high rates of PRCA. METHODS: Ten previously reported candidate tag SNPs were genotyped and/or imputed in the 8q24 region in 532 AB men with PRCA and 513 AB controls from the Prostate Cancer in a Black Population (PCBP) study. RESULTS: Rs2124036 was significant in AB men, (OR = 2.7, 95% CI (1.3-5.3), P = 0.005, Empirical (max (T), corrected for multiple testing) P = 0.03) for the homozygous C/C genotype. Only a single SNP from this region remained statistically significant in our analysis of our AB population. These results may indicate the presence of a founder effect or due to the chosen SNPs not tagging an ancestral haplotype bearing the 8q24 risk allele(s) in this population or could reflect inadequate power to detect an association. We conducted a meta-analysis including our AB population along with two additional African Caribbean populations from Tobago and Jamaica for SNPs rs16901979 and rs1447295. Meta-analysis results were most significant for rs16901979 A allele (Z score 2.73; P = 0.006) with a summary OR = 1.31 (95% CI: 1.09-1.58). CONCLUSIONS: Additional studies are needed to provide deeper genotype coverage to further interrogate the 8q24 region to understand its contribution to PRCA in this population.

Diabetes mortality: trends and multi-country analysis of the Americas from 2000 to 2019.

BACKGROUND: Diabetes has been increasing worldwide and is now among the 10 leading causes of death globally. Diabetic kidney disease (DKD), a complication of poorly managed diabetes, is related to high mortality risk. To better understand the situation in the Americas region, we evaluated diabetes and DKD mortality trends over the past 20 years. METHODS: We analysed diabetes and DKD mortality for 33 countries in the Americas from 2000 to 2019. Data were extracted from the World Health Organization (WHO) Global Health Estimates and the World Population Prospects, 2019 Revision, estimating annual age-standardized mortality rates (ASMR) and gaps in the distribution of diabetes and DKD mortality by sex and country. Trend analyses were based on the annual average percentage of change (AAPC). RESULTS: From 2000 to 2019, the overall mortality trend from diabetes in the Americas remained stable [AAPC: -0.2% (95% CI: -0.4%-0.0%]; however, it showed important differences by sex and by country over time. By contrast, DKD mortality increased 1.5% (1.3%-1.6%) per year, rising faster in men than women, with differences between countries. Central America, Mexico and the Latin Caribbean showed significant increases in mortality for both diseases, especially DKD. In contrast in North America, diabetes mortality decreased whereas DKD mortality increased. CONCLUSIONS: The increase in DKD mortality is evidence of poorly controlled diabetes in the region. The lack of programmes on prevention of complications, self-care management and gaps in quality health care may explain this trend and highlight the urgent need to build more robust health systems based on primary care, prioritizing diabetes prevention and control.

Forecasting the impact of means restriction on the suicide mortality rate in the Region of the Americas: an ecological modeling study.

Background: The suicide mortality rate has been increasing in Region of the Americas, despite decreasing in all other World Health Organization (WHO) regions. Means restriction is an effective evidence-based intervention for suicide prevention. The objective of the current study was to estimate the impact of implementing national-level means restriction policies (i.e., firearm and pesticide restrictions) on the suicide mortality rate in the Region of the Americas. Methods: In this ecological modeling study, two counterfactual scenarios were investigated using sex-specific suicide mortality data from the WHO Global Health Estimates database for 2000 to 2019. Forecasted sex-specific age-standardized suicide mortality rates were then estimated for each country for 2020 to 2030. Counterfactual scenario 1 involved modeling the impact of a firearm or pesticide restriction implemented in 2020 for those countries where the respective means accounted for 40% or more of all suicides for at least one sex in 2019, while in counterfactual scenario 2 this threshold was reduced to 20% or more. Findings: It was estimated that if a firearm or pesticide restriction had been implemented in 2020 in those countries where the respective means accounted for 40% or more of all suicides for at least one sex in 2019, by 2030 the male and female suicide mortality rate in the Region of the Americas would be 20.5% (from 14.5 [95% Confidence Interval [CI]: 14.1, 15.0] per 100,000 males to 11.5 [95% CI: 11.1, 12.0] per 100,000 males) and 11.1% (from 4.5 [95% CI: 4.4, 4.7] per 100,000 females to 4.0 [95% CI: 3.9, 4.2] per 100,000 females) lower than the rate if no such restrictions were implemented, respectively. When the threshold was reduced to 20% or more, minimal additional gains in terms of number of suicides avoided and suicide mortality rate reduction would be achieved. Interpretation: The implementation of a firearm or pesticide restriction policy in countries where the respective means account for a large proportion of suicides (e.g., at least 40%) could aid the Region of the Americas in achieving the WHO target of a one third reduction in the suicide mortality rate by 2030. Funding: This work received no funding.

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.

Fine mapping of breast cancer genome-wide association studies loci in women of African ancestry identifies novel susceptibility markers.

Numerous single nucleotide polymorphisms (SNPs) associated with breast cancer susceptibility have been identified by genome-wide association studies (GWAS). However, these SNPs were primarily discovered and validated in women of European and Asian ancestry. Because linkage disequilibrium is ancestry-dependent and heterogeneous among racial/ethnic populations, we evaluated common genetic variants at 22 GWAS-identified breast cancer susceptibility loci in a pooled sample of 1502 breast cancer cases and 1378 controls of African ancestry. None of the 22 GWAS index SNPs could be validated, challenging the direct generalizability of breast cancer risk variants identified in Caucasians or Asians to other populations. Novel breast cancer risk variants for women of African ancestry were identified in regions including 5p12 (odds ratio [OR] = 1.40, 95% confidence interval [CI] = 1.11-1.76; P = 0.004), 5q11.2 (OR = 1.22, 95% CI = 1.09-1.36; P = 0.00053) and 10p15.1 (OR = 1.22, 95% CI = 1.08-1.38; P = 0.0015). We also found positive association signals in three regions (6q25.1, 10q26.13 and 16q12.1-q12.2) previously confirmed by fine mapping in women of African ancestry. In addition, polygenic model indicated that eight best markers in this study, compared with 22 GWAS-identified SNPs, could better predict breast cancer risk in women of African ancestry (per-allele OR = 1.21, 95% CI = 1.16-1.27; P = 9.7 × 10(-16)). Our results demonstrate that fine mapping is a powerful approach to better characterize the breast cancer risk alleles in diverse populations. Future studies and new GWAS in women of African ancestry hold promise to discover additional variants for breast cancer susceptibility with clinical implications throughout the African diaspora.

The rising burden of non-communicable diseases in the Americas and the impact of population aging: a secondary analysis of available data.

Background: Public health progress in the Americas has reduced the burden of many infectious diseases, helping more people live longer lives. At the same time, the burden of non-communicable diseases (NCDs) is increasing. NCD prevention rightly focuses on lifestyle risk factors, social, and economic determinants of health. There is less published information on the importance of population growth and aging to the regional NCD burden. Methods: For 33 countries in the Americas, we used United Nations population data to describe rates of population growth and aging over two generations (1980-2060). We used World Health Organization estimates of mortality and disability (disability-adjusted life years, DALYs) to describe changes in the NCD burden between 2000 and 2019. After combining these data resources, we decomposed the change in the number of deaths and DALYs to estimate the percentage change due to population growth, due to population aging, and due to epidemiological advances, measured by changing mortality and DALY rates. In a supplement, we provide a summary briefing for each country. Findings: In 1980, the proportion of the regional population aged 70 and older was 4.6%. It rose to 7.8% by 2020 and is predicted to rise to 17.4% by 2060. Across the Americas, DALY rate reductions would have decreased the number of DALYs by 18% between 2000 and 2019 but was offset by a 28% increase due to population aging and a 22% increase due to population growth. Although the region enjoyed widespread reductions in rates of disability, these improvements have not been sufficiently large to offset the pressures of population growth and population aging. Interpretation: The region of the Americas is aging and the pace of this aging is predicted to increase. The demographic realities of population growth and population aging should be factored into healthcare planning, to understand their implications for the future NCD burden, the health system needs, and the readiness of governments and communities to respond to those needs. Funding: This work was funded in part by the Pan American Health Organization, Department of Noncommunicable Diseases and Mental Health.

Recurrent BRCA1 and BRCA2 mutations in breast cancer patients of African ancestry.

Recurrent mutations constituted nearly three quarters of all BRCA1 mutations and almost half of all BRCA2 mutations identified in the first cohort of the Nigerian Breast Cancer Study. To further characterize breast/ovarian cancer risks associated with BRCA1/BRCA2 mutations in the African diaspora, we genotyped recurrent mutations among Nigerian, African American, and Barbadian breast cancer patients. A replication cohort of 356 Nigerian breast cancer patients was genotyped for 12 recurrent BRCA1/2 mutant alleles (Y101X, 1742insG, 4241delTG, M1775R, 4359insC, C64Y, 1623delTTAAA, Q1090X, and 943ins10 from BRCA1, and 1538delAAGA, 2630del11, and 9045delGAAA from BRCA2) by means of SNaPshot followed by direct sequencing or by direct sequencing alone. In addition, 260 African Americans and 118 Barbadians were genotyped for six of the recurrent BRCA1 mutations by SNaPshot assay. Of all the BRCA1/2 recurrent mutations we identified in the first cohort, six were identified in 11 patients in the replication study. These mutation carriers constitute 3.1 % [95 % Confidence Interval (CI) 1.6-5.5 %] of the replication cohort. By comparison, 6.9 % (95 % CI 4.7-9.7 %) of the discovery cohort carried BRCA1/2 recurrent mutations. For the subset of recurrent mutations we tested in breast cancer cases from Barbados or the United States, only two 943ins10 carriers were identified in African Americans. Nigerian breast cancer patients from Ibadan carry a broad and unique spectrum of BRCA1/2 mutations. Our data suggest that BRCA1/2 mutation testing limited to recurrent mutations is not sufficient to understand the BRCA1/2-associated breast cancer risk in African populations in the diaspora. As the cost of Sanger sequencing is considerably reduced, deploying innovative technologies such as high throughput DNA sequencing of BRCA1/2 and other cancer susceptibility genes will be essential for identifying high-risk individuals and families to reduce the burden of aggressive early onset breast cancer in low-resource settings.