Association between lifestyle risk factors and mortality in the Mexico City prospective study.

Unhealthy lifestyles risk factors, such as smoking, alcohol consumption, physical inactivity, poor diet, and obesity, have been associated with a higher risk of all-cause and cause-specific mortality. However, composite score of these unhealthy behaviours has not been considered, particularly in Latin American populations. Herein, we examined the association of lifestyle risk factors score with all-cause and cause-specific mortality in Mexican adults. A total of 159,517 adults from the Mexico City Prospective Study (MCPS) were included. Data on sociodemographic, lifestyle risk factors and medical histories was collected through a self-reported baseline questionnaire in a census-style door-to-door interviews. Lifestyle risk factors assessment was based on five modifiable lifestyle risk factors and their respective cut-off points according to current health recommendations, including obesity, physical inactivity, tobacco, alcohol consumption and fruits and vegetables intake. Multivariable Cox regression models were used to estimate the associations of lifestyle risk factor score (ranging from 0 to 5) with all-cause and cause-specific mortality (cardiovascular disease, renal or hepatobiliary diseases, diabetes, respiratory diseases, cancer and all-cause mortality). We excluded the first 2, 5, 10, and 15 years of follow-up to account for reverse causation bias. We found a high prevalence (77%) of Mexican adults, with two or more lifestyle risk factors. Hazard ratio for respiratory diseases and renal or hepatobiliary diseases were 1.86 (95%CI: 1.45-2.39) and 2.00 (95%CI: 1.60-2.52) comparing participants with 4-5 lifestyle risk factors vs. those with none. For all-cause mortality, participants with 4-5 lifestyle risk factors had a 49% (HR: 1.49; 95%CI: 1.03-2.16) higher risk as compared to participants with none. The magnitude of the associations increased as the exclusion of follow-up time increased after 2, 5, 10 and 15 years. There was a positive association between the number of lifestyle risk factors and all-cause and cause-specific mortality, showing the highest rate of respiratory, renal or hepatobiliary and all-cause mortality among participants with 4-5 lifestyle risk factors. After accounting for reverse causation, associations were stronger.

Causes and investigation of stillbirths in Brazil: A multicentre cross-sectional study in 10 referral maternity hospitals.

OBJECTIVE: Understanding the local characteristics and statistics related to stillbirths may be the first step in a series of strategies associated with a reduction in stillbirth ratio. The aim of this study was to estimate the fetal mortality ratio and evaluate the investigation processes related to the causes of death, comparing the investigation according to the specific cause of death. METHODS: A cross-sectional study was retrospectively conducted in 10 tertiary obstetric care centers. Medical records of women with stillbirth managed between January 1, 2009 and December 31, 2018 were analyzed and classified, according to sociodemographic characteristics, and gestational and childbirth data, culminating in stillbirth. The stillbirth ratio and its causes were presented in proportions for the study period and individually for each health facility. RESULTS: Cases of 3390 stillbirths were analyzed. The stillbirth ratio varied from 10.74/1000 live births (LBs) in 2009 to 9.31/1000 in 2018. "Intrauterine hypoxia and asphyxia" (ICD-10 P20) and "unspecific causes of death" (ICD-10 P95) represented 40.8% of the causes of death. Investigation for TORCHS and diabetes occurred in 90.8% and 61.4% of deaths, respectively. Placental and necroscopic tests were performed in 36.6% of the cases. CONCLUSION: The adoption of a rational and standardized investigation of stillbirth remains an unmet need; the use of additional tests and examinations are lacking, especially when unspecific causes are attributed.

Overall survival and cause-specific mortality in a hospital-based cohort of retinoblastoma patients in São Paulo, Brazil.

Studies are lacking on long-term effects among retinoblastoma patients in low- and middle-income countries. Therefore, we examined cause-specific mortality in a retrospective cohort of retinoblastoma patients treated at Antonio Candido de Camargo Cancer Center (ACCCC), São Paulo, Brazil from 1986 to 2003 and followed up through December 31, 2018. Vital status and cause of death were ascertained from medical records and multiple national databases. We estimated overall and cause-specific survival using the Kaplan-Meier survival method, and estimated standardized mortality ratios (SMRs) and absolute excess risk (AER) of death. This cohort study included 465 retinoblastoma patients (42% hereditary, 58% nonhereditary), with most (77%) patients diagnosed at advanced stages (IV or V). Over an 11-year average follow-up, 80 deaths occurred: 70% due to retinoblastoma, 22% due to subsequent malignant neoplasms (SMNs) and 5% to non-cancer causes. The overall 5-year survival rate was 88% consistent across hereditary and nonhereditary patients (p = .67). Hereditary retinoblastoma patients faced an 86-fold higher risk of SMN-related death compared to the general population (N = 16, SMR = 86.1, 95% CI 52.7-140.5), corresponding to 42.4 excess deaths per 10,000 person-years. This risk remained consistent for those treated with radiotherapy and chemotherapy (N = 10, SMR = 90.3, 95% CI 48.6-167.8) and chemotherapy alone (N = 6, SMR = 80.0, 95% CI 35.9-177.9). Nonhereditary patients had only two SMN-related deaths (SMR = 7.2, 95% CI 1.8-28.7). There was no excess risk of non-cancer-related deaths in either retinoblastoma form. Findings from this cohort with a high proportion of advanced-stage patients and extensive chemotherapy use may help guide policy and healthcare planning, emphasizing the need to enhance early diagnosis and treatment access in less developed countries.

The effect of economic crisis and austerity measures on deaths of despair in Brazil: An interrupted time series analysis.

Some recent analyses have described that, in the context of the instability of social protection institutions and economic crisis, there is an increase in mortality rates selectively from drug overdoses, suicides and alcohol-related liver diseases. This group of causes was named "Deaths of Despair. In the last decade, Brazil experienced economic stagnation and fiscal austerity, influencing the profile of illnesses and deaths. Therefore, our study aimed to evaluate the effect of the economic crisis and fiscal austerity measures on deaths of despair in Brazil and to describe the trend of deaths of despair in Brazil between 2003 and 2018, according to the phases of the economic cycle. We analyzed the time series of rates by covariates and fitted an interrupted time series model to assess the effect of the crisis on the trend through the Prais-Winsten method. The temporal analysis showed a significant difference in the mean values ​ before and after economic stagnation (Mean 8.68 ± 0.71) and after (Mean 11.62 ± 0.62). We found a positive association between the economic crisis and deaths of despair, with a significant change in level (p-value = 0.003) and a non-significant trend effect (p-value = 0.300). There are differences in sex, age, and especially race: men, middle-aged and black/brown people are more at risk. The present study presents the effect of the economic crisis and mortality in the population, with demographic differences.

Conditional cash transfers and mortality in people hospitalised with psychiatric disorders: A cohort study of the Brazilian Bolsa Família Programme.

BACKGROUND: Psychiatric patients experience lower life expectancy compared to the general population. Conditional cash transfer programmes (CCTPs) have shown promise in reducing mortality rates, but their impact on psychiatric patients has been unclear. This study tests the association between being a Brazilian Bolsa Família Programme (BFP) recipient and the risk of mortality among people previously hospitalised with any psychiatric disorders. METHODS AND FINDINGS: This cohort study utilised Brazilian administrative datasets, linking social and health system data from the 100 Million Brazilian Cohort, a population-representative study. We followed individuals who applied for BFP following a single hospitalisation with a psychiatric disorder between 2008 and 2015. The outcome was mortality and specific causes, defined according to International Classification of Diseases 10th Revision (ICD-10). Cox proportional hazards models estimated the hazard ratio (HR) for overall mortality and competing risks models estimated the HR for specific causes of death, both associated with being a BFP recipient, adjusted for confounders, and weighted with a propensity score. We included 69,901 psychiatric patients aged between 10 and 120, with the majority being male (60.5%), and 26,556 (37.99%) received BFP following hospitalisation. BFP was associated with reduced overall mortality (HR 0.93, 95% CI 0.87,0.98, p 0.018) and mortality due to natural causes (HR 0.89, 95% CI 0.83, 0.96, p < 0.001). Reduction in suicide (HR 0.90, 95% CI 0.68, 1.21, p = 0.514) was observed, although it was not statistically significant. The BFP's effects on overall mortality were more pronounced in females and younger individuals. In addition, 4% of deaths could have been prevented if BFP had been present (population attributable risk (PAF) = 4%, 95% CI 0.06, 7.10). CONCLUSIONS: BFP appears to reduce mortality rates among psychiatric patients. While not designed to address elevated mortality risk in this population, this study highlights the potential for poverty alleviation programmes to mitigate mortality rates in one of the highest-risk population subgroups.

Association of potassium disorders with the mode of death and etiology in patients with chronic heart failure: the INCOR-HF study.

Observational studies suggest a U-shaped association between serum potassium (K⁺) levels and mortality in patients with chronic heart failure (CHF). However, the mode of death in patients with HF and K⁺ disorders remains speculative. To investigate the association between potassium disorders and the mode of death in patients with CHF. A retrospective cohort of 10,378 CHF outpatients was analyzed over an average of 3.28 ± 2.5 years. Kaplan-Meier method, Cox proportional hazards regression models, Poisson regression models adjusting for confounders, and e-value determination (e' > 1.6) were used to observe associations between potassium disorders and outcomes. Chagas etiology (p < 0.01) and triple HF therapy (p < 0.01) were associated with hyperkalemia. Atrial fibrillation was associated with hypokalemia (p < 0.01). Chronic kidney disease (CKD) (p < 0.01) and diabetes (p = 0.03) were associated with both. Hypertension was inversely related to hyperkalemia (p < 0.01); age was inversely related to hypokalemia. Associations with mortality were significant for Chagas (p < 0.01, e-value 2.16), stroke (p < 0.01, e-value 1.85), hypokalemia (p = 0.02, e-value 1.94), severe hyperkalemia (p = 0.08, e-value 1.93), and CKD (p < 0.01, e-value > 1.63). Decompensated HF or cardiogenic shock was the cause of death in 54% of patients with normokalemia, 67.8% with hypokalemia, 44.9% with mild hyperkalemia, 57.8% with moderate hyperkalemia, and 69% with severe hyperkalemia. Most patients with hypokalemia and severe hyperkalemia died from decompensated HF (p = 0.007). Data suggest hypokalemia and severe hyperkalemia, along with Chagas and CKD, are associated with death. Unexpectedly, progressive HF was the most frequent mode of death rather than arrhythmias. Further studies are needed to confirm these findings and explore the underlying mechanisms.

[Estimates of mortality from external causes in Brazil, 2010-2019: methodology for redistribution of garbage causes]. / Estimativas de mortalidade por causas externas no Brasil, 2010-2019: metodologia de redistribuição de causas garbage.

Insufficient quality of the underlying cause of death in the Brazilian Mortality Information System (SIM), acronym in Portuguese underlists violence and it is necessary to redistribute garbage causes (GC) into valid causes in public health prevention. This study estimated mortality from external causes using the GC redistribution method (GBD-Brazil) and compared it with SIM and estimated data from the GBD-IHME study from 2010 to 2019 in Brazil and its states. The GBD-Brazil GC redistribution algorithm applies previous steps of the GBD-IHME with modifications, using two criteria: proportion of target causes (valid) or reclassification of investigated causes. The SIM data were not adjusted. Standardized rates by direct method, local regression in the time series, and the ratio of the GBD-Brazil and SIM rates are used as correction factors for traffic injuries, falls, suicides, and homicides. Brazil recorded 1.34 million deaths with valid external causes and 171,700 CG in ten years. The redistribution of GC from GBD-Brazil increased valid causes by 12.2%, and the trend curve of the rates was similar to that found with SIM data, but diverged from each other and from the GBD-IHME in states in the North and Northeast regions. The GBD-Brazil estimates changed the pattern of external causes in the states, applying greater corrections to falls in the states of the North and Northeast and homicides in the other states. The GBD-Brazil method can be used in the analysis of violent deaths because it seeks greater methodological simplicity, which guarantees both replication by public managers and consistency of the estimated data, considering the local composition of the data in the redistribution process.

A qualidade insuficiente da causa básica de óbito no Sistema de Informações sobre Mortalidade (SIM) subenumera as violências, e se faz necessária a redistribuição das causas garbage (CG) em causas válidas na prevenção em saúde pública. Este estudo estimou a mortalidade de causas externas usando método de redistribuição de CG (GBD-Brasil), e comparou com dados do SIM e estimados do estudo GBD-IHME de 2010 a 2019 no Brasil e Unidades Federativas (UF). O algoritmo de redistribuição das CG do GBD-Brasil aplica etapas prévias do GBD-IHME com modificações, usando dois critérios: proporção das causas-alvo (válidas) ou reclassificação de causas investigadas. Os dados do SIM estão sem correção. Utiliza-se taxas padronizadas por método direto, regressão local na série temporal e razão das taxas GBD-Brasil e SIM como fator de correção para lesões de trânsito, quedas, suicídios e homicídios. O Brasil registrou 1,34 milhão de óbitos com causas externas válidas e 171.700 CG em 10 anos. A redistribuição de CG do GBD-Brasil aumentou em 12,2% as causas válidas, e a curva de tendência das taxas foi semelhante à encontrada com dados do SIM, mas divergem entre si e com o GBD-IHME em UFs do Norte e do Nordeste. As estimativas do GBD-Brasil mudaram o padrão das causas externas nas UFs, aplicando maiores correções em quedas nas UFs do Norte e do Nordeste e homicídios nas demais UFs. O método GBD-Brasil pode ser utilizado na análise de mortes violentas por buscar maior simplicidade metodológica, que garante tanto replicação por gestores públicos como consistência do dado estimado, considerando a composição local do dado no processo de redistribuição.

La calidad insuficiente de la causa de muerte en el Sistema de Información de Mortalidad brasileño (SIM) subestima la violencia, por lo cual es necesario redistribuir las causas garbage (CG) en causas válidas en la prevención de la salud pública. Este estudio estimó la mortalidad por causas externas por el método de redistribución de CG (GBD-Brasil) y la comparó con los datos de SIM y con los datos estimados del estudio GBD-IHME de 2010 a 2019 por el país (Brasil) y sus estados. El algoritmo de redistribución de CG del GBD-Brasil aplica los pasos anteriores de GBD-IHME con modificaciones, utilizando dos criterios: proporción de causas objetivo (válidas) o reclasificación de las causas investigadas. Los datos del SIM no están corregidos. Las tasas estandarizadas se utilizan método directo, regresión local en las series de tiempo y relación de tasas GBD-Brasil y SIM como factor de corrección para lesiones de tráfico, caídas, suicidios y homicidios. Brasil registró 1,34 millones de muertes por causas externas válidas y 171.700 CG en diez años. La redistribución de CG de GBD-Brasil aumentó las causas válidas en un 12,2%, y la curva de tendencia de las tasas fue similar a la encontrada con los datos SIM, pero divergieron entre sí y con el GBD-IHME en los estados del Norte y Nordeste. Las estimaciones del GBD-Brasil cambiaron el patrón de causas externas en los estados mediante la aplicación de mayores correcciones a las caídas en los estados del Norte y Nordeste y a los homicidios en los otros estados. El método GBD-Brasil se puede utilizar en el análisis de muertes violentas porque es una metodología más simple, lo que garantiza tanto la replicación por parte de los gestores públicos como la consistencia de los datos estimados, teniendo en cuenta la composición local de los datos en el proceso de redistribución.

Maternal mortality in Panama from 1998 to 2022 / Mortalidad materna en Panamá entre 1998 y el 2022 / Mortalidade materna no Panamá de 1998 a 2022

[ABSTRACT]. Objective. To examine maternal mortality in Panama, analyzing its direct obstetric deaths, indirect obstetric deaths, and contributory conditions. Methods. This cohort study used publicly available data from the National Institute of Statistics and Census to present a 25-year retrospective analysis of maternal deaths in the Republic of Panama from 1998 to 2022. Public data were sourced from the National Institute of Statistics and Census website of Panama. Relevant codes from the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD) were used. The maternal mortality ratio (MMR) was defined as the number of maternal deaths per 100 000 live births. Trendline reliability with R2 was performed to analyze the data. Results. A total of 1 026 maternal deaths occurred in Panama from 1998 through 2022, of which 61.2% were attributed to direct obstetric causes; 23.9%, indirect obstetric causes; 13.6%, contributory conditions; and 1.4% were unknown or undetermined. The average MMR was 60.1. The trendline reliability resulted in R2 = 0.1 (y = –0.5147x + 1094.7), which is not statistically significant but meets the 2030 Sustainable Development Goals. The specific primary causes of direct obstetric deaths were: 12.9% due to postpartum hemorrhage (ICD O72); 9.2%, eclampsia (ICD O15); 6.7%, puerperal sepsis (ICD O85); and 6.3%, pre-eclampsia (ICD O14). For indirect obstetric deaths, the primary causes were: 14.9% due to other maternal diseases classifiable elsewhere but complicating pregnancy, childbirth, and the puerperium (ICD O99); and 7.3%, maternal infectious and parasitic diseases classifiable elsewhere but complicating pregnancy, childbirth, and the puerperium (ICD O98). Conclusions. The findings of this study confirmed that there were substantially more direct obstetric causes (61.2%) than indirect obstetric causes (23.9%), contributory causes (13.6%), or unknown/undetermined causes (1.4%) of maternal mortality, despite being highly preventable. Although Panama is right on track to fulfill the target of 70 MMR by 2030, these results highlight the lack of health care access due to the absence of obstetrician-gynecologists per 100 000 population in indigenous comarcas, where 30.8% of the maternal mortalities occur. Furthermore, the health system in Panama is not immune to pandemics and crises. From 1998 to 2022, there were 5 years when the MMR in Panama exceeded 70: 2001, 2002, 2006, 2011, and 2020. These findings also underscore the dichotomy between statistics and health policy. While the trendline reliability was insignificant (R2 = 0.1), the MMR satisfies requirements for the 2030 Sustainable Development Goals. Future studies should consider factors related to indirect obstetrics and contributory causes of deaths, health care access, COVID-19, cesarean section and natural birth, age, economic income, prenatal and postpartum care, as well as the quality of private and public health facilities in the Americas.

[RESUMEN]. Objetivo. Examinar la mortalidad materna en Panamá mediante el análisis de las muertes obstétricas directas e indirectas y las debidas a afecciones que contribuyen a producirlas. Métodos. Para este estudio de cohorte se utilizaron datos de acceso público del Instituto Nacional de Estadística y Censo, con el fin de presentar un análisis retrospectivo de 25 años de la mortalidad materna en República de Panamá entre 1998 y el 2022. Los datos públicos se obtuvieron del sitio web del Instituto Nacional de Estadística y Censo de Panamá. Se utilizaron los códigos pertinentes de la Clasificación Estadística Internacional de Enfermedades y Problemas Relacionados con la Salud, décima revisión (CIE-10). Se definió la razón de mortalidad materna (RMM) como el número de muertes maternas por cada 100 000 nacidos vivos. Los datos se analizaron mediante la fiabilidad de la línea de tendencia con el cálculo de R2. Resultados. Entre 1998 y el 2022 se registraron en Panamá 1026 muertes maternas, de las cuales el 61,2% se atribuyó a causas obstétricas directas; el 23,9% a causas obstétricas indirectas; el 13,6% a afecciones que contribuyen a producirlas; y el 1,4% a causas desconocidas o indeterminadas. La RMM media fue de 60,1. La fiabilidad de la línea de tendencia mostró un valor de R2 = 0,1 (y = –0,5147x + 1094,7), que no alcanza significación estadística, pero cumple con los Objetivos de Desarrollo Sostenible para el 2030. Las principales causas específicas de las muertes obstétricas directas fueron: un 12,9% por hemorragia posparto (CIE O72); un 9,2%, por eclampsia (CIE O15); un 6,7%, por sepsis puerperal (CIE O85); y un 6,3%, por preeclampsia (CIE O14). En el caso de las muertes obstétricas indirectas, las causas principales fueron: un 14,9% por enfermedades maternas clasificadas bajo otro concepto pero que complican el embarazo, parto y puerperio (CIE O99); y un 7,3%, por enfermedades infecciosas y parasitarias maternas clasificadas bajo otro concepto pero que complican el embarazo, parto y puerperio (CIE O98). Conclusiones. Los resultados de este estudio confirmaron que, a pesar de ser en gran parte prevenible, la mortalidad materna se debió en mayor medida a las causas obstétricas directas (61,2%) que a las indirectas (23,9%), las afecciones que contribuyen a producirla (13,6%) o a las causas desconocidas o indeterminadas (1,4%). Aunque Panamá está en camino de cumplir con el objetivo de una RMM de 70 para el 2030, estos resultados ponen de manifiesto la falta de acceso a la atención de salud en las comarcas indígenas, donde se produce el 30,8% de la mortalidad materna, debido al reducido número de obstetras y ginecólogos por cada 100 000 habitantes. Además, el sistema de salud de Panamá no es inmune a las pandemias y las crisis. Entre 1998 y el 2022, hubo cinco años en los que la RMM fue superior a 70: 2001, 2002, 2006, 2011 y 2020. Estos resultados también subrayan la dicotomía existente entre las estadísticas y las políticas de salud. Si bien la fiabilidad de la línea de tendencia no fue significativa (R2 = 0,1), su valor cumple con los requisitos de los Objetivos de Desarrollo Sostenible para el 2030. En estudios futuros se deberán tener en cuenta los factores relacionados con la mortalidad debida a causas obstétricas indirectas y afecciones que contribuyen a producirla, el acceso a la atención de salud, la COVID-19, las cesáreas y los partos naturales, la edad, los ingresos económicos, la atención prenatal y puerperal, así como la calidad de los establecimientos de salud privados y públicos de la Región de las Américas.

[RESUMO]. Objetivo. Examinar a mortalidade materna no Panamá por meio de uma análise das mortes obstétricas diretas, mortes obstétricas indiretas e fatores contribuintes. Métodos. Este estudo de coorte usa dados publicamente disponíveis do Instituto Nacional de Estatística e Censo do Panamá para apresentar uma análise retrospectiva de um período de 25 anos de mortes maternas na República do Panamá, de 1998 a 2022. Os dados públicos foram obtidos no site do Instituto Nacional de Estatística e Censo. Foram usados códigos relevantes da Classificação Estatística Internacional de Doenças e Problemas Relacionados à Saúde, Décima Revisão (CID). A razão de mortalidade materna (RMM) foi definida como o número de mortes maternas por 100 mil nascidos vivos. Para analisar os dados, determinou-se a confiabilidade da linha de tendência usando R2. Resultados. Houve 1 026 mortes maternas no Panamá de 1998 a 2022. Dessas, 61,2% foram atribuídas a causas obstétricas diretas; 23,9%, a causas obstétricas indiretas; 13,6%, a fatores contribuintes; e 1,4% tinham causa desconhecida ou indeterminada. A RMM média foi de 60,1. Na análise da confiabilidade da linha de tendência, obteve-se R2 = 0,1 (y = -0,5147x + 1094,7), o que não é estatisticamente significante, mas atende aos Objetivos de Desenvolvimento Sustentável para 2030. As causas primárias específicas de mortes obstétricas diretas foram: 12,9% devido a hemorragia pós-parto (CID O72); 9,2%, eclâmpsia (CID O15); 6,7%, infecção puerperal (CID O85); e 6,3%, pré-eclâmpsia (CID O14). No caso das mortes obstétricas indiretas, as principais causas foram: 14,9% devido a outras doenças da mãe, classificadas em outra parte mas que complicam a gravidez, o parto e o puerpério (CID O99); e 7,3%, doenças infecciosas e parasitárias maternas classificáveis em outra parte, mas que compliquem a gravidez, o parto e o puerpério (CID O98). Conclusões. Os achados deste estudo confirmaram que houve um número substancialmente maior de causas obstétricas diretas (61,2%) que de causas obstétricas indiretas (23,9%), fatores contribuintes (13,6%) ou causas desconhecidas ou indeterminadas (1,4%) de mortalidade materna, apesar de essas causas serem altamente preveníveis. Embora o Panamá esteja no rumo certo para cumprir a meta de RMM de 70 até 2030, esses resultados destacam a falta de acesso à atenção à saúde devido ao déficit de ginecologistas-obstetras por 100 mil habitantes nas comarcas indígenas, onde se concentram 30,8% das mortes maternas. Além disso, o sistema de saúde do Panamá não é imune a pandemias e crises. Entre 1998 e 2022, houve cinco anos em que a RMM no Panamá passou de 70: 2001, 2002, 2006, 2011 e 2020. Estes achados também realçam a dicotomia entre as estatísticas e as políticas de saúde. Embora a confiabilidade da linha de tendência não tenha sido significante (R2 = 0,1), a RMM cumpre os requisitos dos Objetivos de Desenvolvimento Sustentável para 2030. Futuros estudos devem considerar fatores relacionados às causas obstétricas indiretas e contribuintes das mortes, acesso à atenção à saúde, COVID-19, cesariana e parto natural, idade, renda econômica e assistência pré-natal e pós-parto, bem como a qualidade dos estabelecimentos de saúde públicos e privados na Região das Américas.

Sexual minorities cardiovascular health disparities compared to heterosexual adults in the US: a systematic review and meta-analysis of nearly 2 million cohort patients

BACKGROUND: Cardiovascular disease (CVD) remains a leading cause of death globally, yet disparities in CVD outcomes among sexual minorities compared to heterosexual adults are under-researched. Sexual minorities face unique stressors, discrimination, and barriers to healthcare, which may contribute to higher CVD risk. This meta-analysis synthesizes evidence on health disparities between sexual minorities and heterosexual adults. METHODS: We searched MEDLINE, Cochrane, and Embase databases for studies published between 2002 to 2024 that compared cardiovascular health disparities between sexual minorities and their heterosexual counterparts. Outcomes were CVD, Diabetes, Hypertension, and Obesity. We pooled odds ratios (OR) for binary endpoints with 95% confidence intervals (CI) using a random-effects model. Statistical analyses were performed using R software version 4.3.2. RESULTS: We included 9 Cross-sectional studies after minimizing population overlap, comprising 1,938,814 patients with a mean age of 47 years. There were no significant differences in the odds of CVD (OR 1.10; 95% CI 0.87 to 1.39; Figure 1 A), Diabetes (OR 0.88; 95% CI 0.74 to 1.04; Figure 1 B), hypertension (OR 1.07; 95% CI 0.97 to 1.19; Figure 2 A) and Obesity (OR 1.01; 95% CI 0.76 to 1.35; Figure 2 B) between groups. In subgroup analysis, there were higher odds of obesity in the sexual minority population when compared to their heterosexual counterparts (OR 1.29; 95 % CI 1.15 to 1.45) and higher hypertension odds in sexual minority men (OR 1.35; 95% CI 1.12 to 1.63). CONCLUSION: In this meta-analysis, we found no statistically significant difference in the prevalence of CVD, diabetes, and obesity between sexual minorities and heterosexuals, meaning that more studies are necessary to assess this difference. Subgroup analyses revealed sexual minority men had higher odds of hypertension and sexual minority women for obesity.

Association between low-density lipoprotein cholesterol levels and all-cause mortality in patients with coronary artery disease: a real-world analysis using data from an international network.

The current cholesterol guidelines recommend maintaining low levels of low-density lipoprotein cholesterol (LDL-C) in patients with coronary artery disease (CAD). However, recent studies have suggested that both very low and very high LDL-C levels may be associated with increased mortality in the general population. We utilized data from TriNetX, a global health research network, to investigate the association between LDL-C levels and all-cause mortality in patients with CAD. CAD patients were identified using the International Classification of Diseases, Tenth Revision (ICD-10) diagnosis code and stratified into six LDL-C categories: <50 mg/dL (cohort 1), 50-69.9 mg/dL (cohort 2), 70-99.9 mg/dL (cohort 3), 100-129.9 mg/dL (cohort 4), 130-159.9 mg/dL (cohort 5), and ≥ 160 mg/dL (cohort 6). Mortality data were obtained by linking patient records to death registries spanning the 15 years prior to the analysis. Weighted Cox proportional hazards regression models were employed to estimate hazard ratios (HRs) for mortality outcomes along with their 95% confidence intervals (CIs). A total of 2,145,732 individuals with CAD (mean age 72 years, SD 13; mean LDL-C 87.7 mg/dL, SD 37.7) were included in the analysis. Over a 15-year follow-up period, 191,779 deaths (8.9%) were recorded. After propensity score matching, patients with LDL-C < 50 mg/dL (37.05% vs. 33.11%, HR 1.144, 95% CI 1.125-1.164, p < 0.0001), LDL-C 130-159.9 mg/dL (26.47% vs. 25.71%, HR 1.032, 95% CI 1.007-1.059, p = 0.0136), and LDL-C ≥ 160 mg/dL (26.29% vs. 24.38%, HR 1.121, 95% CI 1.082-1.163, p < 0.0001) demonstrated a higher risk of all-cause mortality compared to those with LDL-C 100-129.9 mg/dL. Conversely, patients with LDL-C 50-69.9 mg/dL (27.88% vs. 29.68%, HR 0.898, 95% CI 0.883-0.913, p = 0.0002) and LDL-C 70-99.9 mg/dL (26.21% vs. 27.84%, HR 0.908, 95% CI 0.893-0.923, p = 0.0057) exhibited a lower risk of all-cause mortality compared to the reference group (LDL-C 100-129.9 mg/dL). In conclusion, our findings suggest a U-shaped relationship between LDL-C levels and all-cause mortality in patients with CAD, where both very low (< 50 mg/dL) and high (≥ 130 mg/dL) LDL-C levels are associated with increased mortality risk. These results highlight the need for individualized LDL-C targets in managing patients with CAD.

Alcohol and mortality in Mexico: prospective study of 150 000 adults.

BACKGROUND: Alcohol consumption is a leading cause of premature death globally, but there is no large-scale prospective evidence from Mexico. METHODS: The Mexico City Prospective Study recruited 150 000 adults aged 35 years or older between 1998 and 2004. Participants were followed up until Oct 1, 2022 for cause-specific mortality. Cox regression in those with no self-reported chronic disease at entry (adjusted for age, sex, district, education, physical activity, smoking, and diabetes) was used to relate baseline-reported alcohol consumption (never, former, occasional [less than monthly], and regular [at least monthly, split into <70, ≥70 to <140, ≥140 to <210, and ≥210 g/week]) to mortality at ages 35-74 from all causes, and from a pre-specified alcohol-related set of underlying causes. Heavy episodic drinking (normally consuming >5 [men] or >4 [women] drinks on a single occasion) and type of preferred drink were also examined. FINDINGS: Among 138 413 participants aged 35-74 years at recruitment, 21 136 (15%) were regular alcohol drinkers (14 863 [33%] men, 6273 [7%] women), of whom 13 383 (63%) favoured spirits and 6580 (31%) favoured beer. During follow-up, there were 13 889 deaths at ages 35-74 years, including 3067 deaths from the pre-specified alcohol-related causes. Overall, J-shaped associations with mortality were observed. Compared with occasional drinkers, those with baseline-reported consumption ≥210 g/week had 43% higher all-cause mortality (rate ratio [RR] 1·43 [95% CI 1·30-1·56]) and nearly three times the mortality from the pre-specified alcohol-related causes (2·77 [2·39-3·20]). Death from liver disease was strongly related to alcohol consumption; the RR comparing regular drinkers of ≥140 g/week with occasional drinkers was 4·03 (3·36-4·83). Compared with occasional light drinking, occasional heavy episodic drinking was associated with 20% higher alcohol-related mortality (1·20 [1·06-1·35]), and regular heavy episodic drinking was associated with 89% higher alcohol-related mortality (1·89 [1·67-2·15]). Drinks with alcohol percentages higher than spirits were associated with the greatest increased mortality risk, even after accounting for the total alcohol consumed. INTERPRETATION: In this Mexican population, higher alcohol consumption, episodic drinking, and very high percentage alcoholic products were all associated with increased mortality. FUNDING: Wellcome Trust, the Mexican Health Ministry, the National Council of Science and Technology for Mexico, Cancer Research UK, British Heart Foundation, and the UK Medical Research Council. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Seasonality as a risk factor for deaths in Parkinson's disease.

BACKGROUND: According to growing evidence, sleep disruption harms biological processes and circadian homeostasis. Diurnal motor symptom volatility in Parkinson's Disease (PD) has been extensively studied. Few studies examined seasonal variability in PD symptoms, some showing it and others not. OBJECTIVE: To investigate whether PD patients' deaths follow a rhythmic pattern due to circadian rhythm alterations. METHODS: This study used only unidentified patient databases. People with PD, ICD10 code G20, in at least one death certificate field were selected. The Continuous Wavelet Transform and Fourier Transform were checked for oscillation and its duration. RESULTS: The 18-year analysis found 43,072 PD deaths. The Continuous Wavelet transform revealed a 351.87-day annual component (p < 0.05). Winter in the southern hemisphere saw more deaths, mainly in July. The Continuous Wavelet transform identified a significant daily component (p < 0.05) of 22.81 hours. Fatalities peaked around 9 a.m. Pneumonia is the leading cause of death in PD, and women and men have the same rhythm pattern. CONCLUSION: Parkinson's disease mortality in Brazil follows a pattern. Using over 40.000 death certificates from 18 years, the authors found that Parkinson's patient fatalities rise in winter and peak in July at about 9 a.m. Sunlight reduction increases mortality risk in the long term. Low sunshine lowers temperatures, increasing short-term death risk. This is crucial because it prioritizes the sun, seasons, and circadian rhythm over low temperatures.

Excess potential years of working life lost in six countries from Latin America and Europe in 2020 and 2021.

OBJECTIVE: This descriptive study aimed to measure the excess all-cause mortality potential years of working life lost (PYWLL) in the working-age population of six Ibero-American countries in 2020 and 2021. METHODS: This study was based on all-cause deaths for the age group 15-69 years for men and women in six countries: Colombia, Costa Rica, México, Peru, Portugal and Spain. The expected PYWLL was the average value determined from the previous 5 years (2015-2019). To estimate the excess of PYWLL, the expected PYWLL was subtracted from the observed PYWLL values for 2020 and 2021, separately. RESULTS: In the four Latin American countries, the excess PYWLL per death was approximately double (between 12 and 16 years) that of the two European countries (between 3 and 9 years). CONCLUSIONS: The loss of working-age individuals will probably have a profound social and economic recovery impact, affecting families and communities. The informal employment and labour market structures may be contributing to the adverse effects of the pandemic in the region. Investing in universal, comprehensive and sustainable health and social protection systems in the Latin American countries is crucial to build resilience against current and future crises.

The leading causes of death in the US and Mexico's pediatric population are related to violence: a note on secondary analyses of registered deaths from 2000 to 2022.

Introduction: our objective was to analyze the trends in the leading causes of death among the pediatric population aged 1-19 years in Mexico and the United States (US) from 2000 to 2022. Methods. Data for Mexico were sourced from the National Institute of Statistics and Geography (INEGI), while the US data were extracted from the Centers for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research (CDC-WONDER) databases. Results: Homicide has been the leading cause of death since 2017 in Mexico and since 2019 in US youths aged 1-19. In Mexico, it reached 6.5 deaths per 100,000 people in 2022. Despite the overall pediatric mortality decline from 2000 to 2022 in both countries, the pediatric homicide rate has increased by 93.3 and 35.8% In Mexico and the US, respectively, and suicide by 86.6 and 36.9%. In both countries, death by firearm-related injuries had risen in a parallel sense. In the US, deaths by drug overdose and poisoning have increased by 314.8%. Conclusion: Despite advancements in infant healthcare over the past two decades in Mexico, there remains a significant gap in the provision of healthcare services to the adolescent population. Addressing issues related to violence, mental health, and substance abuse through targeted public policies is imperative for both Mexico and the US, especially given their shared border region.

The Impact of Severe Heart Disease on Causes of Death and Survival after Disability Retirement. / O Impacto da Cardiopatia Grave nas Causas de Óbito e Sobrevida após Aposentadoria por Invalidez.

BACKGROUND: Noncommunicable diseases contribute to premature deaths and limitations. Disability retirement is linked to chronic conditions, particularly cardiovascular diseases. The II Brazilian Guideline for Severe Heart Disease established criteria for cardiovascular disease classification. However, there is a lack of research in this topic within federal institutions. OBJECTIVES: Evaluate the survival and causes of death among disabled retirees at UFRJ, focusing on the impact of severe heart disease. METHODS: A retrospective cohort study based on retirement and death records over 15 years. Retirements were categorized into three groups: full retirement due to severe heart disease, full retirement due to other diseases and proportional. Causes of death were obtained from death certificates. Mortality rates, survival and the presence of matching diagnoses between retirement and death were evaluated. Chi-square, log-rank, Cox models, Kaplan-Meier curves were utilized. Statistical significance with a 95% confidence interval, considering p<0.05. RESULTS: There were 630 retirements, 368 (51.4%) in females, with an average age of 52.9 (SD=7.8) years, and 169 (26.8%) deaths. Mortality was higher in professors (37.0%; p=0.113), in the age group between 65 and 70 years (48.4%; p=0.004), in males (34.0%; p=0.001), and in full retirements due to severe heart disease (41.5%; p<0.001). Matching diagnoses between retirement and death were more frequent in professors (74.1%; p=0.026) and in full retirements due to severe heart disease (72.7%; p<0.001). CONCLUSIONS: Severe heart disease diagnosis is associated with higher mortality and shorter survival in disabled retirees. Its frequent occurrence in retirement and death diagnoses underscores its significance in this context.

FUNDAMENTO: As doenças não comunicáveis são responsáveis por mortes prematuras e limitações. A aposentadoria por invalidez está associada a condições crônicas, especialmente a doenças cardiovasculares. A II Diretriz Brasileira de Cardiopatia Grave definiu critérios para enquadramento das doenças cardiovasculares. Poucos estudos abordam esse tema em instituições federais. OBJETIVOS: Avaliar sobrevida e causas de óbito de servidores aposentados por invalidez na UFRJ, com ênfase no impacto da cardiopatia grave. MÉTODOS: Estudo de coorte retrospectivo baseado nos registros de aposentadorias e óbitos ao longo de 15 anos. As aposentadorias foram divididas em três grupos: integral por cardiopatia grave, integral por outras doenças e proporcional. As causas de óbito foram obtidas a partir das certidões de óbito. Foram avaliadas taxa de mortalidade, sobrevida e a presença de diagnósticos concordantes entre a aposentadoria e o óbito. Foram utilizados testes qui-quadrado, log-rank, modelos de Cox e curvas de Kaplan-Meier. Significância estatística com intervalo de confiança de 95%, considerando p < 0,05. RESULTADOS: Foram 630 aposentadorias, 368 (51,4%) no sexo feminino, com idade média de idade de 52,9 (DP=7,8) anos, e 169 (26,8%) óbitos. A mortalidade foi maior nos professores (37,0%; p=0,113), na faixa etária entre 65 e 70 anos (48,4%; p=0,004), no sexo masculino (34,0%; p=0,001), e nas aposentadorias integrais por cardiopatia grave (41,5%; p < 0,001). Diagnósticos concordantes entre aposentadoria e óbito foram mais frequentes em professores (74,1%; p=0,026) e nas aposentadorias integrais por cardiopatia grave (72,7%; p < 0,001). CONCLUSÕES: O diagnóstico de cardiopatia grave confere maior taxa de mortalidade e menor sobrevida aos aposentados por invalidez, e sua presença em maior frequência nos diagnósticos de aposentadoria e óbito ressalta sua importância neste contexto.

Escalating Health Crisis: Dissecting Mortality Causes and Trends Among Indigenous Populations in Northeast Brazil.

OBJECTIVES: In Northeast Brazil, the poorest region of the country, indigenous communities face critical health care challenges. Despite legal entitlements to the Unified Health System (SUS), systemic barriers persist, exacerbating health disparities and mortality. This ecological study analyzed mortality trends and causes of death within the Special Indigenous Sanitary District (DSEI) Alagoas-Sergipe over a decade. METHODS: Data on deaths from 2012 to 2022 were obtained from the Indigenous Health Secretariat. Causes of death were classified into 13 categories. Mortality rates per 1,000 indigenous inhabitants were calculated, and trends were analyzed using the Mann-Kendall test. The study also compared causes of death by age group. RESULTS: Mortality rates ranged from 3.3 to 5.2 per 1,000, showing a moderate upward trend over time (τ = 0.5, p = 0.042). Predominant causes included heart and vascular disorders (24.3%), external causes (12.4%), respiratory issues (11.1%), and infections (10.9%). About one-third of pediatric deaths were associated with general neonatal complications. CONCLUSIONS: This study highlights increasing mortality in indigenous communities in Northeast Brazil. The predominant causes of death reflect broader public health concerns. These trends emphasize the urgency for more effective, culturally sensitive public health policies and improved health care access.

Spatio-temporal trends in mortality due to Chagas disease in the State of Bahia, Brazil, from 2008 to 2018.

BACKGROUND: Chagas disease is a silent illness with high mortality burden in many Latin American countries, such as Brazil. Bahia has the fourth highest mortality rate in Brazil. This study analyzed the temporal trends and regional differences in the mortality rate of Chagas disease in Bahia State from 2008 to 2018. METHODS: A time-series analysis of Chagas disease-related deaths was conducted using data from the Mortality Information System of Brazil. We compared the mortality rate due to Chagas disease as the primary cause and mention of the disease in the death certificate, standardized by age and health macroregion/residence municipality, and mapped hot and coldspots. RESULTS: The Chagas Disease Mortality Rate in Bahia during the study period revealed a stationary trend, ranging from 5.34 (2008) to 5.33 (2018) deaths per 100,000 inhabitants. However, the four health macroregions showed an upward trend in mortality rates. The mortality rate (age-adjusted) ranged from 4.3 to 5.1 deaths per 100,000 inhabitants between 2008 and 2018. We observed a upward trend in the mortality rate among individuals aged ≥70 years and a higher incidence of death among men than among women. Of the total number of deaths (8,834), 79.3% had Chagas disease as the primary cause and the death certificates of 20.7% mentioned the disease. Cardiac complications were reported in 85.1% of the deaths due to Chagas disease. CONCLUSIONS: The regional and individual differences in the mortality rate of Chagas disease highlighted in this study may support health planning that considers the peculiarities of the territory.

Survival and predictors of mortality in patients with heart failure in the cardiology department of the Center Hospitalier Basse Terre in Guadeloupe: historical cohort study.

BACKGROUND: Despite the progress made in recent years in the treatment of Acute Heart Failure (AHF), its prognosis remains poor in the developing country. The objective of this study is to analyze the survival and predictors of mortality of patients with acute heart failure in the cardiology department of the Basse Terre Hospital Center in Guadeloupe. METHODS: this was a historical cohort study carried out over a period from June 2021 to June 2022, targeting all acute heart failure patients undergoing cardiac monitoring in the cardiology department of the Basse Terre Hospital Center in Guadeloupe. Sociodemographic, clinical, biological characteristics and outcome (recovery or death) were studied. Survival was described using the Kaplan Meier method α = 5%. RESULTS: this study involved 242 acute heart failure patients whose median age was 75 years and the majority were male (sex ratio 2 M/1F). Among these patients, 14.9% died, the most common cause of death was cardiogenic shock (52.8%). After adjustment, tobacco consumption (aHR: 2.90; 95% CI: 1.36-8.09), Chronic Kidney Disease (aHR: 2.52; 95% CI: 1.22-5.20), infection (aHR: 2.14; 95CI %: 1.99-4.58), hyponatremia (aHR: 1.90; 95% CI: 1.10-2.86), mitral regurgitation (aHR: 3.04; 95% CI: 1.98-9.47) and N-terminal pro Brain Natriuretic Peptide > 10000ng/ml (aHR: 2.57; 95% CI: 1.21-5.49) were independently associated with the risk of death in heart failure patients. CONCLUSION: Acute heart failure leads to high mortality, mainly due to cardiogenic shock and factors of multiple organ failure.

Underreporting of diabetes mellitus as the cause of death in Bauru, State of São Paulo, Brazil over 40 years: a documental study.

Objective: To evaluate, characterize and search for trends in the underreporting of diabetes mellitus (DM) as the cause of death in Bauru, São Paulo, Brazil, over 40 years. Subjects and methods: This was a documental study. Clinical and mortality data were collected from individuals known to have type 1 (DM1) and type 2 diabetes mellitus (DM2), residing in Bauru, State of São Paulo, followed at a local endocrinology clinic from 1982 to 2021, who deceased during this period. Results: A significant underreporting of DM as the cause of death (64.41%) was found, mostly associated with male gender (OR = 1.59 [95% CI: 1.18; 2.15]; p < 0.01), DM2 (OR = 2.64 [95% CI: 1.32; 5.26]; p < 0.01), dying in the first decade of the study (OR = 4.07 [95% CI: 1.54; 10.71]; p < 0.001) and shorter DM duration (OR = 1.02 [95% CI: 1.01; 1.04]; p < 0.01). Age, type of treatment, body mass index, marital status and ethnicity, did not show a significant association with DM underreporting. There was a decreasing trend in DM1 underreporting (Decade Percentual Change = -7.10 [95% CI: -11.35; -3.40]), but a stationary trend for DM and DM2. The main primary cause of death was cardiovascular-related complications. Conclusion: The underreporting of DM as the cause of death was very frequently found, and was associated with male gender, decade of death, shorter DM duration and DM2. If our data could be applied to the whole country, DM would possibly emerge as a more prominent cause of death in Brazil. Future studies in other cities and geographic regions are warranted to confirm our findings.

Interleukin-receptor antagonist and tumour necrosis factor inhibitors for the primary and secondary prevention of atherosclerotic cardiovascular diseases.

BACKGROUND: Atherosclerotic cardiovascular disease (ACVD) is worsened by chronic inflammatory diseases. Interleukin receptor antagonists (IL-RAs) and tumour necrosis factor-alpha (TNF) inhibitors have been studied to see if they can prevent cardiovascular events. OBJECTIVES: The purpose of this study was to assess the clinical benefits and harms of IL-RAs and TNF inhibitors in the primary and secondary prevention of ACVD. SEARCH METHODS: The Cochrane Heart Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE (including In-Process & Other Non-Indexed Citations), Ovid Embase, EBSCO CINAHL plus, and clinical trial registries for ongoing and unpublished studies were searched in February 2024. The reference lists of relevant studies, reviews, meta-analyses and health technology reports were searched to identify additional studies. No limitations on language, date of publication or study type were set. SELECTION CRITERIA: RCTs that recruited people with and without pre-existing ACVD, comparing IL-RAs or TNF inhibitors versus placebo or usual care, were selected. The primary outcomes considered were all-cause mortality, myocardial infarction, unstable angina, and adverse events. DATA COLLECTION AND ANALYSIS: Two or more review authors, working independently at each step, selected studies, extracted data, assessed the risk of bias and used GRADE to judge the certainty of evidence. MAIN RESULTS: We included 58 RCTs (22,053 participants; 21,308 analysed), comparing medication efficacy with placebo or usual care. Thirty-four trials focused on primary prevention and 24 on secondary prevention. The interventions included IL-1 RAs (anakinra, canakinumab), IL-6 RA (tocilizumab), TNF-inhibitors (etanercept, infliximab) compared with placebo or usual care. The certainty of evidence was low to very low due to biases and imprecision; all trials had a high risk of bias. Primary prevention: IL-1 RAs The evidence is very uncertain about the effects of the intervention on all-cause mortality(RR 0.33, 95% CI 0.01 to 7.58, 1 trial), myocardial infarction (RR 0.71, 95% CI 0.04 to 12.48, I² = 39%, 2 trials), unstable angina (RR 0.24, 95% CI 0.03 to 2.11, I² = 0%, 2 trials), stroke (RR 2.42, 95% CI 0.12 to 50.15; 1 trial), adverse events (RR 0.85, 95% CI 0.59 to 1.22, I² = 54%, 3 trials), or infection (rate ratio 0.84, 95% 0.55 to 1.29, I² = 0%, 4 trials). Evidence is very uncertain about whether anakinra and cankinumab may reduce heart failure (RR 0.21, 95% CI 0.05 to 0.94, I² = 0%, 3 trials). Peripheral vascular disease (PVD) was not reported as an outcome. IL-6 RAs The evidence is very uncertain about the effects of the intervention on all-cause mortality (RR 0.68, 95% CI 0.12 to 3.74, I² = 30%, 3 trials), myocardial infarction (RR 0.27, 95% CI 0.04 to1.68, I² = 0%, 3 trials), heart failure (RR 1.02, 95% CI 0.11 to 9.63, I² = 0%, 2 trials), PVD (RR 2.94, 95% CI 0.12 to 71.47, 1 trial), stroke (RR 0.34, 95% CI 0.01 to 8.14, 1 trial), or any infection (rate ratio 1.10, 95% CI: 0.88 to 1.37, I2 = 18%, 5 trials). Adverse events may increase (RR 1.13, 95% CI 1.04 to 1.23, I² = 33%, 5 trials). No trial assessed unstable angina. TNF inhibitors The evidence is very uncertain about the effects of the intervention on all-cause mortality (RR 1.78, 95% CI 0.63 to 4.99, I² = 10%, 3 trials), myocardial infarction (RR 2.61, 95% CI 0.11 to 62.26, 1 trial), stroke (RR 0.46, 95% CI 0.08 to 2.80, I² = 0%; 3 trials), heart failure (RR 0.85, 95% CI 0.06 to 12.76, 1 trial). Adverse events may increase (RR 1.13, 95% CI 1.01 to 1.25, I² = 51%, 13 trials). No trial assessed unstable angina or PVD. Secondary prevention: IL-1 RAs The evidence is very uncertain about the effects of the intervention on all-cause mortality (RR 0.94, 95% CI 0.84 to 1.06, I² = 0%, 8 trials), unstable angina (RR 0.88, 95% CI 0.65 to 1.19, I² = 0%, 3 trials), PVD (RR 0.85, 95% CI 0.19 to 3.73, I² = 38%, 3 trials), stroke (RR 0.94, 95% CI 0.74 to 1.2, I² = 0%; 7 trials), heart failure (RR 0.91, 95% 0.5 to 1.65, I² = 0%; 7 trials), or adverse events (RR 0.92, 95% CI 0.78 to 1.09, I² = 3%, 4 trials). There may be little to no difference between the groups in myocardial infarction (RR 0.88, 95% CI 0.0.75 to 1.04, I² = 0%, 6 trials). IL6-RAs The evidence is very uncertain about the effects of the intervention on all-cause mortality (RR 1.09, 95% CI 0.61 to 1.96, I² = 0%, 2 trials), myocardial infarction (RR 0.46, 95% CI 0.07 to 3.04, I² = 45%, 3 trials), unstable angina (RR 0.33, 95% CI 0.01 to 8.02, 1 trial), stroke (RR 1.03, 95% CI 0.07 to 16.25, 1 trial), adverse events (RR 0.89, 95% CI 0.76 to 1.05, I² = 0%, 2 trials), or any infection (rate ratio 0.66, 95% CI 0.32 to 1.36, I² = 0%, 4 trials). No trial assessed PVD or heart failure. TNF inhibitors The evidence is very uncertain about the effect of the intervention on all-cause mortality (RR 1.16, 95% CI 0.69 to 1.95, I² = 47%, 5 trials), heart failure (RR 0.92, 95% 0.75 to 1.14, I² = 0%, 4 trials), or adverse events (RR 1.15, 95% CI 0.84 to 1.56, I² = 32%, 2 trials). No trial assessed myocardial infarction, unstable angina, PVD or stroke. Adverse events may be underestimated and benefits inflated due to inadequate reporting. AUTHORS' CONCLUSIONS: This Cochrane review assessed the benefits and harms of using interleukin-receptor antagonists and tumour necrosis factor inhibitors for primary and secondary prevention of atherosclerotic diseases compared with placebo or usual care. However, the evidence for the predetermined outcomes was deemed low or very low certainty, so there is still a need to determine whether these interventions provide clinical benefits or cause harm from this perspective. In summary, the different biases and imprecision in the included studies limit their external validity and represent a limitation to determining the effectiveness of the intervention for both primary and secondary prevention of ACVD.