Smoking, all-cause, and cause-specific mortality in individuals with diabetes in Mexico: an analysis of the Mexico city prospective study.

OBJECTIVE: Evidence from low- and middle-income countries regarding the effect of smoking in people with diabetes is lacking. Here, we report the association of smoking with mortality in a large cohort of Mexican adults with diabetes. METHODS: Participants with diabetes mellitus (self-reported diagnosis, use of antidiabetic medications or HbA1c ≥ 6.5%) aged 35-74 years when recruited into the Mexico City Prospective Study were included. Cox regression confounder-adjusted mortality rate ratios (RRs) associated with baseline smoking status were estimated. RESULTS: Among 15,975 women and 8225 men aged 35-74 years with diabetes but no other comorbidities at recruitment, 2498 (16%) women and 2875 (35%) men reported former smoking and 2753 (17%) women, and 3796 (46%) men reported current smoking. During a median of 17 years of follow-up there were 5087 deaths at ages 35-74 years. Compared with never smoking, all-cause mortality RR was 1.08 (95%CI 1.01-1.17) for former smoking, 1.11 (95%CI 1.03-1.20) for current smoking, 1.09 (95%CI 0.99-1.20) for non-daily smoking, 1.06 (95%CI 0.96-1.16) for smoking < 10 cigarettes/day (median during follow-up 4 cigarettes/day), and 1.28 (95% CI 1.14-1.43) for smoking ≥ 10 cigarettes/day (median during follow-up 15 cigarettes/day). Mortality risk among daily smokers was greatest for COPD, lung cancer, cardiovascular diseases, and acute diabetic complications. CONCLUSION: In this cohort of Mexican adults with diabetes, low-intensity daily smoking was associated with increased mortality, despite observing smoking patterns which are different from other populations, and over 5% of total deaths were associated with smoking.

Prediabetes as a risk factor for all-cause and cause-specific mortality: a prospective analysis of 115,919 adults without diabetes in Mexico City.

BACKGROUND: Prediabetes has been associated with increased all-cause and cardiovascular mortality. However, no large-scale studies have been conducted in Mexico or Latin America examining these associations. METHODS: We analyzed data from 115,919 adults without diabetes (diagnosed or undiagnosed) aged 35-84 years who participated in the Mexico City Prospective Study between 1998 and 2004. Participants were followed until January 1st, 2021 for cause-specific mortality. We defined prediabetes according to the American Diabetes Association (ADA, HbA1c 5.7% to 6.4%) and the International Expert Committee (IEC, HbA1c 6.0-6.4%) definitions. Cox regression adjusted for confounders was used to estimate all-cause and cause-specific mortality rate ratios (RR) at ages 35-74 years associated with prediabetes. FINDINGS: During 2,085,392 person-years of follow-up (median in survivors 19 years), there were 6,810 deaths at ages 35-74, including 1,742 from cardiovascular disease, 892 from renal disease and 108 from acute diabetic crises. Of 110,405 participants aged 35-74 years at recruitment, 28,852 (26%) had ADA-defined prediabetes and 7,203 (7%) had IEC-defined prediabetes. Compared with those without prediabetes, individuals with prediabetes had higher risk of all-cause mortality at ages 35-74 years (RR 1.13, 95% CI 1.07-1.19 for ADA-defined prediabetes and RR 1.28, 1.18-1.39 for IEC-defined prediabetes), as well as increased risk of cardiovascular mortality (RR 1.22 [1.10-1.35] and 1.42 [1.22-1.65], respectively), renal mortality (RR 1.35 [1.08-1.68] and 1.69 [1.24-2.31], respectively), and death from an acute diabetic crisis (RR 2.63 [1.76-3.94] and 3.43 [2.09-5.62], respectively). RRs were larger at younger than at older ages, and similar for men compared to women. The absolute excess risk associated with ADA and IEC-defined prediabetes at ages 35-74 accounted for6% and 3% of cardiovascular deaths respectively, 10% and 5% of renal deaths respectively, and 31% and 14% of acute diabetic deaths respectively. INTERPRETATION: Prediabetes is a significant risk factor for all-cause, cardiovascular, renal, and acute diabetic deaths in Mexican adults. Identification and timely management of individuals with prediabetes for targeted risk reduction could contribute to reducing premature mortality from cardiometabolic causes in this population. FUNDING: Wellcome Trust, the Mexican Health Ministry, the National Council of Science and Technology for Mexico, Cancer Research UK, British Heart Foundation, UK Medical Research Council. Instituto Nacional de Geriatría (Mexico City).

Characterising the contribution of rare protein-coding germline variants to prostate cancer risk and severity in 37,184 cases.

The etiology of prostate cancer, the second most common cancer in men globally, has a strong heritable component. While rare coding germline variants in several genes have been identified as risk factors from candidate gene and linkage studies, the exome-wide spectrum of causal rare variants remains to be fully explored. To more comprehensively address their contribution, we analysed data from 37,184 prostate cancer cases and 331,329 male controls from five cohorts with germline exome/genome sequencing and one cohort with imputed array data from a population enriched in low-frequency deleterious variants. Our gene-level collapsing analysis revealed that rare damaging variants in SAMHD1 as well as genes in the DNA damage response pathway (BRCA2, ATM and CHEK2) are associated with the risk of overall prostate cancer. We also found that rare damaging variants in AOX1 and BRCA2 were associated with increased severity of prostate cancer in a case-only analysis of aggressive versus non-aggressive prostate cancer. At the single-variant level, we found rare non-synonymous variants in three genes (HOXB13, CHEK2, BIK) significantly associated with increased risk of overall prostate cancer and in four genes (ANO7, SPDL1, AR, TERT) with decreased risk. Altogether, this study provides deeper insights into the genetic architecture and biological basis of prostate cancer risk and severity.

Epidemia de diabetes tipo 2 en México. Análisis de la carga de la enfermedad 1990-2021 e implicaciones en la política pública / Type 2 diabetes epidemic in Mexico. Burden of disease 1990-2021 analysis and implications for public policies

Resumen Antecedentes: México enfrenta un desafío por la carga que representa la diabetes tipo 2 (DT2). Objetivo: Analizar la epidemiología y la carga de DT2 en México de 1990 a 2021 en los ámbitos nacional y estatal. Material y métodos: Se empleó el Global Burden of Disease 2021 para evaluar prevalencia, incidencia, mortalidad, carga letal y no letal. Se consideraron factores metabólicos, ambientales y de comportamiento. Se realizó análisis comparativo por sexo, edad y entidad federativa. Resultados: Se incrementó la prevalencia de DT2 en 25 % y la incidencia en menores de 45 años; la mortalidad en mujeres disminuyó. La tasa de años de vida saludable (AVISA) perdidos se incrementó en todos los estados, entre 45.2 % en Nuevo León y 237.6 % en Tabasco. En 2021, la DT2 ocasionó 3.1 millones de AVISA perdidos, que representaron 6.6 % de la carga total en México, de la cual 64 % se atribuyó a muertes prematuras. La neuropatía diabética afectó a 47 % y las afecciones visuales a 270 000 personas; 66.3 % de la carga se atribuyó a obesidad. Conclusiones: Urgen políticas integrales para reducir la carga de DT2 en México, mediante pautas estandarizadas, estrategias basadas en evidencia y recursos tecnológicos que mejoren la accesibilidad y eficiencia de la atención médica.

Abstract Background: Mexico faces a challenge due to the burden imposed by type 2 diabetes (T2D). Objective: To analyze T2D epidemiology and burden in Mexico from 1990 to 2021, at the national and state levels. Material and methods: Estimates from the Global Burden of Disease 2021 study were used to evaluate the prevalence, incidence, mortality, fatal and non-fatal burden. Metabolic, environmental and behavioral factors were considered. Comparative analyses were carried out by gender, age and state of the country. Results: The prevalence of T2D increased by 25%. The incidence increased in those younger than 45 years, with a mortality decrease being found among women. The rate of disability-adjusted life years (DALY) showed an increase in all states, from 45.2% in Nuevo León to 237.6% in Tabasco. In 2021, T2D caused the loss of 3.1 million DALYs, which accounted for 6.6% of total burden in Mexico, out of which 64% was due to premature deaths. Diabetic neuropathy affected 47%, and there were 270,000 cases of visual impairment; 66.3% of the burden was attributed to obesity. Conclusions: Comprehensive policies are urgently needed in order to reduce the burden of T2D in Mexico, through standardized guidelines, evidence-based strategies and technological resources that improve medical care accessibility and efficiency.

Educational and social inequalities and cause-specific mortality in Mexico City: a prospective study.

BACKGROUND: Social inequalities in adult mortality have been reported across diverse populations, but there is no large-scale prospective evidence from Mexico. We aimed to quantify social, including educational, inequalities in mortality among adults in Mexico City. METHODS: The Mexico City Prospective Study recruited 150 000 adults aged 35 years and older from two districts of Mexico City between 1998 and 2004. Participants were followed up until Jan 1, 2021 for cause-specific mortality. Cox regression analysis yielded rate ratios (RRs) for death at ages 35-74 years associated with education and examined, in exploratory analyses, the mediating effects of lifestyle and related risk factors. FINDINGS: Among 143 478 participants aged 35-74 years, there was a strong inverse association of education with premature death. Compared with participants with tertiary education, after adjustment for age and sex, those with no education had about twice the mortality rate (RR 1·84; 95% CI 1·71-1·98), equivalent to approximately 6 years lower life expectancy, with an RR of 1·78 (1·67-1·90) among participants with incomplete primary, 1·62 (1·53-1·72) with complete primary, and 1·34 (1·25-1·42) with secondary education. Education was most strongly associated with death from renal disease and acute diabetic crises (RR 3·65; 95% CI 3·05-4·38 for no education vs tertiary education) and from infectious diseases (2·67; 2·00-3·56), but there was an apparent higher rate of death from all specific causes studied with lower education, with the exception of cancer for which there was little association. Lifestyle factors (ie, smoking, alcohol drinking, and leisure time physical activity) and related physiological correlates (ie, adiposity, diabetes, and blood pressure) accounted for about four-fifths of the association of education with premature mortality. INTERPRETATION: In this Mexican population there were marked educational inequalities in premature adult mortality, which appeared to largely be accounted for by lifestyle and related risk factors. Effective interventions to reduce these risk factors could reduce inequalities and have a major impact on premature 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 Population Health Research Unit.

Rare coding variants in CHRNB2 reduce the likelihood of smoking.

Human genetic studies of smoking behavior have been thus far largely limited to common variants. Studying rare coding variants has the potential to identify drug targets. We performed an exome-wide association study of smoking phenotypes in up to 749,459 individuals and discovered a protective association in CHRNB2, encoding the ß2 subunit of the α4ß2 nicotine acetylcholine receptor. Rare predicted loss-of-function and likely deleterious missense variants in CHRNB2 in aggregate were associated with a 35% decreased odds for smoking heavily (odds ratio (OR) = 0.65, confidence interval (CI) = 0.56-0.76, P = 1.9 × 10-8). An independent common variant association in the protective direction ( rs2072659 ; OR = 0.96; CI = 0.94-0.98; P = 5.3 × 10-6) was also evident, suggesting an allelic series. Our findings in humans align with decades-old experimental observations in mice that ß2 loss abolishes nicotine-mediated neuronal responses and attenuates nicotine self-administration. Our genetic discovery will inspire future drug designs targeting CHRNB2 in the brain for the treatment of nicotine addiction.

Influenza and morbidity and mortality risk in patients in Mexico with systemic arterial hypertension alone or with comorbidities: a retrospective, observational, cross-sectional study from 2014 to 2020.

OBJECTIVES: In Mexico, patients with systemic arterial hypertension (SAH) are excluded from the influenza vaccination programme despite their risk of cardiovascular events as influenza-related complications. We investigated the impact of influenza on morbidity and mortality in patients with SAH. DESIGN: This was a retrospective cross-sectional study that analysed data from early 2014 to mid-2020. SETTING: Data were obtained from the Influenza Epidemiological Surveillance System in Mexico database. PARTICIPANTS: 32 663 cases of influenza in people aged ≥20 years with a confirmed case of influenza-like illness, severe respiratory infection and/or influenza death were investigated. PRIMARY AND SECONDARY OUTCOME MEASURES: Influenza deaths, hospitalisation frequency and the impact on hospitalisation and/or death due to influenza by the SAH variate alone and in combination with diabetes, obesity, chronic obstructive pulmonary disease, cardiovascular disease and/or smoking, and by vaccination status were assessed. RESULTS: The hospitalisation frequency increased with age. Notably, 46.0% (15 033/32 663) of confirmed influenza cases had at least one comorbidity, with SAH (19.2%; 6260/32 663) and obesity (18.7%; 6106/32 663) being the most prevalent. Most confirmed SAH cases (80.8%; 5057/6260) were in those who had not been vaccinated against influenza. There were 3496 deaths due to influenza (mortality rate, 0.69×1 00 000 inhabitants), with the highest rates seen in those aged ≥80 years (80-89 years, 2.0%; ≥90 years, 3.6%). The case fatality rate due to influenza and SAH was significantly higher than those due to influenza without SAH in those aged <50 years, but not in the other age groups (20-29 years, 9.8%, p<0.0005; 30-39 years, 8.2%, p<0.035; 40-49 years, 17.8%, p<0.0005; vs 15.1%-20.0%, p=0.31-0.99 for those aged ≥50 years). CONCLUSIONS: Our findings support the need to include SAH in public policies of influenza vaccination as a secondary prevention measure to avoid fatal outcomes.

Integrated Measurement for Early Detection (MIDO) as a digital strategy for timely assessment of non-communicable disease profiles and factors associated with unawareness and control: a retrospective observational study in primary healthcare facilities in Mexico.

OBJECTIVES: The Carlos Slim Foundation implemented the Integrated Measurement for Early Detection (MIDO), a screening strategy for non-communicable diseases (NCDs) in Mexico as part of CASALUD, a portfolio of digital health services focusing on healthcare delivery and prevention/management of NCDs. We investigated the disease profile of the screened population and evaluated MIDO's contribution to the continuum of care of the main NCDs. DESIGN: Using data from MIDO and the chronic diseases information system, we quantified the proportion of the population screened and diagnosed with NCDs, and measured care linkage/retention and level of control achieved. We analysed comorbidity patterns and estimated prevalence of predisease stages. Finally, we estimated characteristics associated with unawareness and control of NCDs, and examined efficacy of the CASALUD model in improving NCD control. SETTING: Public primary health centres in 27/32 Mexican states. PARTICIPANTS: Individuals aged ≥20 years lacking healthcare access. RESULTS: From 2014 to 2018, 743 000 individuals were screened using MIDO. A predisease or disease condition was detected in ≥70% of the population who were unaware of their NCD status. The screening identified 38 417 new cases of type 2 diabetes, 53 133 new cases of hypertension and 208 627 individuals with obesity. Dyslipidaemia was found in 77.3% of individuals with available blood samples. Comorbidities were highly prevalent, especially in people with obesity. Only 5.47% (n=17 774) of individuals were linked with their corresponding primary health centre. Factors associated with unawareness of and uncontrolled NCDs were sex, age, and social determinants, for example, rural/urban environment, access to healthcare service, and education level. Patients with type 2 diabetes treated at clinics under the CASALUD model were more likely to achieve disease control (OR: 1.32, 95% CI: 1.09 to 1.61). CONCLUSION: Patient-centred screening strategies such as MIDO are urgently needed to improve screening, access, retention and control for patients with NCDs.

Low-intensity daily smoking and cause-specific mortality in Mexico: prospective study of 150 000 adults.

BACKGROUND: Research is needed to determine the relevance of low-intensity daily smoking to mortality in countries such as Mexico, where such smoking habits are common. METHODS: Prospective study of 159 755 Mexican adults recruited from 1998-2004 and followed for cause-specific mortality to 1 January 2018. Participants were categorized according to baseline self-reported smoking status. Confounder-adjusted mortality rate ratios (RRs) at ages 35-89 were estimated using Cox regression, after excluding those with previous chronic disease (to avoid reverse causality). RESULTS: Among 42 416 men and 86 735 women aged 35-89 and without previous disease, 18 985 men (45%) and 18 072 women (21%) reported current smoking and 8866 men (21%) and 53 912 women (62%) reported never smoking. Smoking less than daily was common: 33% of male current smokers and 39% of female current smokers. During follow-up, the all-cause mortality RRs associated with the baseline smoking categories of <10 cigarettes per day (average during follow-up 4 per day) or ≥10 cigarettes per day (average during follow-up 10 per day), compared with never smoking, were 1.17 (95% confidence interval 1.10-1.25) and 1.54 (1.42-1.67), respectively. RRs were similar irrespective of age or sex. The diseases most strongly associated with daily smoking were respiratory cancers, chronic obstructive pulmonary disease and gastrointestinal and vascular diseases. Ex-daily smokers had substantially lower mortality rates than those who were current daily smokers at recruitment. CONCLUSIONS: In this Mexican population, low-intensity daily smoking was associated with increased mortality. Of those smoking 10 cigarettes per day on average, about one-third were killed by their habit. Quitting substantially reduced these risks.

Association of Blood Pressure With Cause-Specific Mortality in Mexican Adults.

Importance: Elevated blood pressure is a major cause of premature death, but there is little direct evidence demonstrating this association in studies of Hispanic populations. Objective: To assess the association between blood pressure and cause-specific mortality in a large cohort of Mexican adults with a high prevalence of uncontrolled diabetes. Design, Setting, and Participants: A total of 159 755 adults aged 35 years or older from 2 districts in Mexico City were recruited to this cohort study between April 1998 and September 2004 and followed up until January 2018. The present analyses focused on 133 613 participants who were aged 35 to 74 years and had no history of chronic disease besides diabetes. Exposure: Blood pressure. Main Outcomes and Measures: Cox regression, adjusted for confounders, yielded mortality rate ratios (RRs) for deaths of participants occurring between ages 35 and 74 years. Results: Of the 133 613 participants (43 263 [32.4%] men; mean [SD] age, 50 [11] years), 16 911 (12.7%) had self-reported previously diagnosed diabetes (including 8435 [6.3%] with uncontrolled diabetes, defined as hemoglobin A1c ≥9%) and 6548 (4.9%) had undiagnosed diabetes. Systolic blood pressure (SBP) was associated with vascular mortality between ages 35 to 74 years, with each 20 mm Hg lower usual SBP associated with 35% lower vascular mortality (RR, 0.65; 95% CI, 0.61-0.68), including 48% lower stroke mortality (RR, 0.52; 95% CI, 0.47-0.59) and 32% lower ischemic heart disease mortality (RR, 0.68; 95% CI, 0.63-0.74). These RRs were broadly similar in those with and without diabetes. Compared with those without diabetes and SBP less than 135 mm Hg at recruitment, the vascular mortality RR was 2.8 (95% CI, 2.4-3.3) for those without diabetes and SBP of 155 mm Hg or greater, 4.7 (95% CI, 4.1-5.4) for those with uncontrolled diabetes and SBP less than 135 mm Hg, and 8.9 (95% CI, 7.2-11.1) for those with uncontrolled diabetes and SBP of 155 mm Hg or greater. Lower SBP was also associated with decreased kidney-related mortality (RR per 20 mm Hg lower usual SBP, 0.69; 95% CI, 0.64-0.74), decreased mortality from infection (RR, 0.81; 95% CI, 0.71-0.91), and decreased mortality from hepatobiliary disease (RR, 0.87; 95% CI, 0.78-0.98), but not decreased neoplastic or respiratory mortality. SBP was more informative for vascular mortality than other blood pressure measures (eg, compared with SBP, diastolic blood pressure was only two-thirds as informative). Conclusions and Relevance: Blood pressure was most strongly associated with vascular and kidney-related mortality in this Mexican population, with particularly high absolute excess mortality rates among individuals with diabetes. The findings reinforce the need for more widespread use of blood pressure-lowering medication in Mexico, particularly among those with diabetes.

General and Abdominal Adiposity and Mortality in Mexico City: A Prospective Study of 150 000 Adults.

Background: Some reports suggest that body mass index (BMI) is not strongly associated with mortality in Hispanic populations. Objective: To assess the causal relevance of adiposity to mortality in Mexican adults, avoiding reverse causality biases. Design: Prospective study. Setting: 2 Mexico City districts. Participants: 159 755 adults aged 35 years and older at recruitment, followed for up to 14 years. Participants with a hemoglobin A1c level of 7% or greater, diabetes, or other chronic diseases were excluded. Measurements: BMI, waist-to-hip ratio, waist circumference, and cause-specific mortality. Cox regression, adjusted for confounders, yielded mortality hazard ratios (HRs) after at least 5 years of follow-up and before age 75 years. Results: Among 115 400 participants aged 35 to <75 years at recruitment, mean BMI was 28.0 kg/m2 (SD, 4.1 kg/m2) in men and 29.6 kg/m2 (SD, 5.1 kg/m2) in women. The association of BMI at recruitment with all-cause mortality was J-shaped, with the minimum at 25 to <27.5 kg/m2. Above 25 kg/m2, each 5-kg/m2 increase in BMI was associated with a 30% increase in all-cause mortality (HR, 1.30 [95% CI, 1.24 to 1.36]). This association was stronger at ages 40 to <60 years (HR, 1.40 [CI, 1.30 to 1.49]) than at ages 60 to <75 years (HR, 1.24 [CI, 1.17 to 1.31]) but was not materially affected by sex, smoking, or other confounders. The associations of mortality with BMI and waist-to-hip ratio were similarly strong, and each was weakened only slightly by adjustment for the other. Waist circumference was strongly related to mortality and remained so even after adjustment for BMI and hip circumference. Limitation: Analyses were limited to mortality. Conclusion: General, and particularly abdominal, adiposity were strongly associated with mortality in this Mexican population. Primary Funding Source: Mexican Health Ministry, Mexican National Council of Science and Technology, Wellcome Trust, Medical Research Council, and Kidney Research UK.

Effect of diabetes duration and glycaemic control on 14-year cause-specific mortality in Mexican adults: a blood-based prospective cohort study.

BACKGROUND: Diabetes is a cause of at least a third of all deaths in Mexican adults aged 35-74 years, with the excess mortality due mainly to vascular disease, renal disease, infection, and acute diabetic crises. We aimed to analyse the effect of diabetes duration and glycaemic control on death rate ratios (RRs) for these causes and to assess the relevance to cause-specific mortality of undiagnosed diabetes. METHODS: About 100 000 women and 50 000 men aged 35 years or older from Mexico City were recruited into a blood-based prospective study between April 14, 1998, and Sept 28, 2004, and followed up until Jan 1, 2016, for cause-specific mortality. Participants who, at recruitment, reported any chronic disease other than diabetes and those who had missing data for HbA1c or diabetes duration were excluded. We used Cox models to estimate the associations of undiagnosed or previously diagnosed diabetes (almost all type 2) with risk of mortality from vascular disease, renal disease, and infection, exploring among those with previously diagnosed diabetes the independent relevance of diabetes duration (<5 years, ≥5 to <10 years, or ≥10 years) and HbA1c (<9%, ≥9% to <11%, or ≥11%). We also estimated the association of HbA1c with mortality in participants without diabetes at recruitment. FINDINGS: 133 662 participants were aged 35-74 years and had complete data and no other chronic disease. 16 940 (13%) had previously diagnosed diabetes, 6541 (5%) had undiagnosed diabetes, and 110 181 (82%) had no diabetes. Among participants with previously diagnosed diabetes, glycaemic control was poor (median HbA1c 8·9% [IQR 7·0-10·9]), and was worse in those with longer duration of disease at recruitment. Compared with participants without diabetes, the death RRs at ages 35-74 years for the combination of vascular, renal, or infectious causes were 3·0 (95% CI 2·7-3·4) in those with undiagnosed diabetes, 4·5 (4·0-5·0) for the 5042 participants with a diabetes duration of less than 5 years, 6·6 (6·1-7·1) for the 7713 participants with a duration of 5 years to less than 10 years, and 11·7 (10·7-12·7) for the 4185 participants with a duration of at least 10 years. Similarly, the death RRs were 5·2 (4·8-5·7) for those with HbA1c less than 9%, 6·8 (6·2-7·4) for those with HbA1c of 9% to less than 11%, and 10·5 (9·7-11·5) for those with HbA1c of at least 11%. Diabetes was not strongly associated with the combination of deaths from other causes apart from acute glycaemic crises. Among participants without diabetes, higher HbA1c was not positively related to mortality. INTERPRETATION: In Mexico, the rates of death from causes strongly associated with diabetes increased steeply with duration of diabetes and were higher still among people with poor glycaemic control. Delaying the onset of type 2 diabetes, as well as improving its treatment, is essential to reduce premature adult mortality in Mexico. FUNDING: Wellcome Trust, the Mexican Health Ministry, the Mexican National Council of Science and Technology, Cancer Research UK, British Heart Foundation, and the UK Medical Research Council Population Health Research Unit.

A Policy Analysis on the Proactive Prevention of Chronic Disease: Learnings from the Initial Implementation of Integrated Measurement for Early Detection (MIDO).

Mexico, like many low- and middle-income countries (LMICs), faces an epidemic of chronic non-communicable diseases (NCDs), specifically diabetes, hypertension, obesity, and lipid disorders. Many people with these NCDs may not be aware that they have a disease, pointing to the need for broader screening programs. The traditional prevention policy in Mexico was based on screening with a paper-based risk factor questionnaire. However, this was used to screen patients already seeking healthcare services at facilities, and screening goals were set as a function of the number of questionnaires applied, not number of individuals screened. Due to this, Fundación Carlos Slim developed Medición Integrada para la Detección Oportuna (MIDOTM), or Integrated Measurement for Early Detection, an NCD screening and proactive prevention policy. This document is a policy analysis based on early learnings from the initial implementation of MIDO in eight primary healthcare centers in two central Mexican states. MIDO was found to expand screening programs beyond clinic walls, systematize community screening strategies, emphasize the detection of pre-disease phases, incorporate lifestyle counseling, and propose screening goals based on population targets. In collaboration with the Mexican Ministry of Health, MIDO has successfully screened over 500 000 individuals-about 40% of whom would not have been screened under previous policies. Of these more than 500 000 screened individuals, 13.4% had pre-diabetes (fasting glucose between 100 and 125 mg/dL), and 5.8% had undiagnosed diabetes (defined as fasting glucose above 126 mg/dL or random glucose above 200 mg/dL). However, there is still room for improvement in linking positive results from screening with disease confirmation and with patient incorporation into disease management. The experience of implementing MIDO in Mexico suggests that primary and secondary prevention programs in other parts of the world should consider the need for population-based screening targets, a greater focus on pre-disease stages, and the streamlining of the transition between screening, confirmation of diagnosis, and incorporation of patients into the healthcare system.

Diabetes and Cause-Specific Mortality in Mexico City.

BACKGROUND: Most large, prospective studies of the effects of diabetes on mortality have focused on high-income countries where patients have access to reasonably good medical care and can receive treatments to establish and maintain good glycemic control. In those countries, diabetes less than doubles the rate of death from any cause. Few large, prospective studies have been conducted in middle-income countries where obesity and diabetes have become common and glycemic control may be poor. METHODS: From 1998 through 2004, we recruited approximately 50,000 men and 100,000 women 35 years of age or older into a prospective study in Mexico City, Mexico. We recorded the presence or absence of previously diagnosed diabetes, obtained and stored blood samples, and tracked 12-year disease-specific deaths through January 1, 2014. We accepted diabetes as the underlying cause of death only for deaths that were due to acute diabetic crises. We estimated rate ratios for death among participants who had diabetes at recruitment versus those who did not have diabetes at recruitment; data from participants who had chronic diseases other than diabetes were excluded from the main analysis. RESULTS: At the time of recruitment, obesity was common and the prevalence of diabetes rose steeply with age (3% at 35 to 39 years of age and >20% by 60 years of age). Participants who had diabetes had poor glycemic control (mean [±SD] glycated hemoglobin level, 9.0±2.4%), and the rates of use of other vasoprotective medications were low (e.g., 30% of participants with diabetes were receiving antihypertensive medication at recruitment and 1% were receiving lipid-lowering medication). Previously diagnosed diabetes was associated with rate ratios for death from any cause of 5.4 (95% confidence interval [CI], 5.0 to 6.0) at 35 to 59 years of age, 3.1 (95% CI, 2.9 to 3.3) at 60 to 74 years of age, and 1.9 (95% CI, 1.8 to 2.1) at 75 to 84 years of age. Between 35 and 74 years of age, the excess mortality associated with previously diagnosed diabetes accounted for one third of all deaths; the largest absolute excess risks of death were from renal disease (rate ratio, 20.1; 95% CI, 17.2 to 23.4), cardiac disease (rate ratio, 3.7; 95% CI, 3.2 to 4.2), infection (rate ratio, 4.7; 95% CI, 4.0 to 5.5), acute diabetic crises (8% of all deaths among participants who had previously diagnosed diabetes), and other vascular disease (mainly stroke). Little association was observed between diabetes and mortality from cirrhosis, cancer, or chronic obstructive pulmonary disease. CONCLUSIONS: In this study in Mexico, a middle-income country with high levels of obesity, diabetes was common, glycemic control was poor, and diabetes was associated with a far worse prognosis than that seen in high-income countries; it accounted for at least one third of all deaths between 35 and 74 years of age. (Funded by the Wellcome Trust and others.).

Universalidad de los servicios de salud en México / Universal Coverage of Health Services in Mexico

Las reformas llevadas a cabo en años recientes al sistema de salud en México han reducido las inequidades en la atención a la salud de la población, pero han sido insuficientes para resolver todos los problemas del Sistema Nacional de Salud (SNS). Para que el derecho a la protección de la salud consagrado en la Constitución sea una realidad para todos los ciudadanos, México se encuentra ante la necesidad de garantizar el acceso universal y efectivo a los servicios de salud. En este trabajo se delinea una reforma de largo alcance para la consolidación de un sistema de salud, afín con estándares internacionales, que establezca las condiciones estructurales para reducir las desigualdades en cobertura. Esta reforma se plantea a partir de un "pluralismo estructurado" para evitar tanto el monopolio ejercido desde el sector público como la atomización en el sector privado, y no caer en los extremos de procedimientos autoritarios o ausencia de regulación. Esto implica sustituir la actual integración vertical con segregación de grupos sociales, por una organización horizontal con separación de funciones. Implica, asimismo, reformas de tipo jurídico y fiscal, fortalecimiento del SNS, reorganización de las instituciones de salud y formulación de los instrumentos normativos, técnicos y financieros que hagan operativo el esquema propuesto para hacer plenamente efectivo el derecho humano a la salud de los mexicanos.

The reforms made in recent years to the Mexican Health System have reduced inequities in the health care of the population, but have been insufficient to solve all the problems of the MHS. In order to make the right to health protection established in the Constitution a reality for every citizen, Mexico must warrant effective universal access to health services. This paper outlines a long-term reform for the consolidation of a health system that is akin to international standards and which may establish the structural conditions to reduce coverage inequity. This reform is based on a "structured pluralism" intended to avoid both a monopoly exercised within the public sector and fragmentation in the private sector, and to prevent falling into the extremes of authoritarian procedures or an absence of regulation. This involves the replacement of the present vertical integration and segregation of social groups by a horizontal organization with separation of duties. This also entails legal and fiscal reforms, the reinforcement of the MHS, the reorganization of health institutions, and the formulation of regulatory, technical and financial instruments to operationalize the proposed scheme with the objective of rendering the human right to health fully effective for the Mexican people.

[Main malignant neoplasms in Mexico and their geographic distribution, 1993-2002]. / Principales neoplasias malignas en México y su distribución geográfica (1993-2002).

UNLABELLED: INTRODUCCION: Cancer is one of the main causes of death worldwide. In Mexico it represents the third cause of death. OBJECTIVE. To know the frequency and distribution of the malignancies diagnosed in Mexico during 10 years. MATERIAL AND METHODS: From the data-base of the histopathological register of malignant neoplasms in Mexico, was obtained a descriptive analysis from the period 1993-2002. The variables included were: city and federative entity of residence, age, sex, anatomical region and histopathologic diagnosis. From the 12 more common malignant neoplasms a descriptive demographic analysis was performed adjusted by four regions: Center, North, South and Federal District. RESULTS: A total of 767,464 cases with cancer were reported. In order of frequency were: cervix-uterine cancer, breast cancer, prostate cancer, lymphomas, colorectal cancer, gastric cancer, sarcomas, ovary cancer, lung cancer, leukemias, urinary bladder cancer and uterine body. Seventy-two percent were diagnosed in women and 28% in men, the reason for a ratio W:M of 2.5:1. The states more developed and industrialized, near to United States had the majority of cases from breast, prostate, ovary and lung cancer. CONCLUSION: There is a distinctive distribution type of malignant tumors in Mexico, according to the region of residence. It absolutely is necessary to developed population based cancer registries. These are the best instruments to better understand the magnitude of cancer, and evaluate incidence, survival and mortality.

Bridging the innovation gap for neglected tropical diseases in México: capacity building for the development of a new generation of antipoverty vaccines

The neglected tropical diseases (NTDs) represent a group of chronic parasitic and related infections that promote poverty because of their impact on child development, pregnancy, and worker productivity. The estimated 20 million Mexicans who live below the poverty line suffer disproportionately from a high prevalence of neglected tropical diseases such as amebiasis, Chagas disease, dengue, leishmaniasis, soil-transmitted helminth infections, trachoma, and vivax malaria. However, because the NTDs occur predominantly among the poor, new industrial and financial models are required to establish innovative technologies to address these conditions in Mexico and elsewhere in Latin America. In response, the Slim Initiative for Antipoverty Vaccine Development was established to foster a public/private partnership between key academic, government, and industrial institutions in the U.S. and Mexico. Initial emphasis will be placed on developing new vaccines for Chagas disease and leishmaniasis, two of the highest burden NTDs in Mexico and Mesoamerica.

Impact of CYP1A1 and COMT genotypes on breast cancer risk in Mexican women: a pilot study.

BACKGROUND: Data suggest that estrogen-metabolizing genes may be involved in breast cancer carcinogenesis. OBJECTIVE: The aim of this study was to determine the association of CYP1A1 and COMT polymorphisms with this disease. MATERIAL AND METHODS: A pilot case-control study was conducted with Mexican women. Ninety-one breast cancer patients and 94 healthy controls were selected. Epidemiological and clinical questionnaires were answered by all participants, and genotyping data were obtained. CYP1A1 3801 T>C (rs4646903), CYP1A1 4889 A>G (rs1048943) and COMT 1947 G>A (rs4680) polymorphisms were analyzed by PCR-RFLP. RESULTS: The results showed a high risk of breast cancer in women carrying the CYP1A1 (3801 T>C) m2/m2 genotype (OR=2.52; 95%CI=1.04-6.08). The risk was higher in postmenopausal women (OR=3.38; 95%CI=1.05-10.87). No association between COMT 1947 G>A (rs4680) or CYP1A1 4889 A>G (rs1048943) and breast cancer was found. CONCLUSIONS: This study suggests that the CYP1A1 (3801 T>C) m2/m2 genotype may contribute to breast cancer susceptibility in Mexican women.