Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990-2013: quantifying the epidemiological transition.

BACKGROUND: The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age-sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. METHODS: We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. FINDINGS: Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6-6·6), from 65·3 years (65·0-65·6) in 1990 to 71·5 years (71·0-71·9) in 2013, HALE at birth rose by 5·4 years (4·9-5·8), from 56·9 years (54·5-59·1) to 62·3 years (59·7-64·8), total DALYs fell by 3·6% (0·3-7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6-29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non-communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. INTERPRETATION: Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition--in which increasing sociodemographic status brings structured change in disease burden--is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions. FUNDING: Bill & Melinda Gates Foundation.

Effective Treatment of Patients Experiencing Primary, Acute HIV Infection Decreases Exhausted/Activated CD4+ T Cells and CD8+ T Memory Stem Cells.

Several studies have identified main changes in T- and B-lymphocyte subsets during chronic HIV infection, but few data exist on how these subsets behave during the initial phase of HIV infection. We enrolled 22 HIV-infected patients during the acute stage of infection before the initiation of antiretroviral therapy (ART). Patients had blood samples drawn previous to ART initiation (T0), and at 2 (T1) and 12 (T2) months after ART initiation. We quantified cellular HIV-DNA content in sorted naïve and effector memory CD4 T cells and identified the main subsets of T- and B-lymphocytes using an 18-parameter flow cytometry panel. We identified correlations between the patients' clinical and immunological data using PCA. Effective HIV treatment reduces integrated HIV DNA in effector memory T cells after 12 months (T2) of ART. The main changes in CD4+ T cells occurred at T2, with a reduction of activated memory, cytolytic and activated/exhausted stem cell memory T (TSCM) cells. Changes were present among CD8+ T cells since T1, with a reduction of several activated subsets, including activated/exhausted TSCM. At T2 a reduction of plasmablasts and exhausted B cells was also observed. A negative correlation was found between the total CD4+ T-cell count and IgM-negative plasmablasts. In patients initiating ART immediately following acute/early HIV infection, the fine analysis of T- and B-cell subsets has allowed us to identify and follow main modifications due to effective treatment, and to identify significant changes in CD4+ and CD8+ T memory stem cells.

Cardiovascular risk factors in young Mexican adults / Factores de riesgo cardiovascular en adultos jóvenes mexicanos

BACKGROUND: Cardiovascular diseases (CVDs) are the main cause of morbidity and mortality in the adult population worldwide. Most studies on risk factors have focused on children and adults of mature age. Quite the opposite, there are few which specifically analyze young individuals. OBJECTIVES: The objectives of the study were to determine cardiovascular risk factors in young Mexican adults. MATERIALS AND METHODS: A cross-sectional, descriptive, and observational study was carried out on a healthy sample of 198 young Mexican university-level adults, aged from 18 to 25 years who, after completing a questionnaire, were evaluated on anthropometric and blood pressure parameters. A comparative analysis of the results was made according to sex and with findings from other studies. RESULTS: In 46% of the subjects, an atherogenic diet was identified (predominant among males). About 59.1% of the individuals were classified as sedentary (mostly women). About 91.4% of the sample had two or more associated antecedents of CVD (and other associated conditions) in their family background, the most frequent being diabetes mellitus (71.2%), systemic hypertension (64.6%), and overweight or obesity (56.6%). In 25.8% of the individuals, overweight was observed (more frequent among women). In males, a higher proportion of alterations in blood pressure levels was described. CONCLUSIONS: The most frequently identified findings correspond to the group of modifiable minor risk factors, which could allow the development of preventive measures, inasmuch as these are subjects in which the modification of harmful behaviors and habits is achievable and timely.

Cardiovascular risk factors in young Mexican adults / Factores de riesgo cardiovascular en adultos jóvenes mexicanos

Abstract Background: Cardiovascular diseases (CVDs) are the main cause of morbidity and mortality in the adult population worldwide. Most studies on risk factors have focused on children and adults of mature age. Quite the opposite, there are few which specifically analyze young individuals. Objectives: The objectives of the study were to determine cardiovascular risk factors in young Mexican adults. Materials and methods: A cross-sectional, descriptive, and observational study was carried out on a healthy sample of 198 young Mexican university-level adults, aged from 18 to 25 years who, after completing a questionnaire, were evaluated on anthropometric and blood pressure parameters. A comparative analysis of the results was made according to sex and with findings from other studies. Results: In 46% of the subjects, an atherogenic diet was identified (predominant among males). About 59.1% of the individuals were classified as sedentary (mostly women). About 91.4% of the sample had two or more associated antecedents of CVD (and other associated conditions) in their family background, the most frequent being diabetes mellitus (71.2%), systemic hypertension (64.6%), and overweight or obesity (56.6%). In 25.8% of the individuals, overweight was observed (more frequent among women). In males, a higher proportion of alterations in blood pressure levels was described. Conclusions: The most frequently identified findings correspond to the group of modifiable minor risk factors, which could allow the development of preventive measures, inasmuch as these are subjects in which the modification of harmful behaviors and habits is achievable and timely.

Resumen Antecedentes: Las enfermedades cardiovasculares (ECV) son la principal causa de morbimortalidad en la población adulta a nivel mundial. La mayor parte de los estudios sobre factores de riesgo han focalizado su atención en niños y adultos de edad madura. Por el contrario, resultan escasos aquellos que analicen específicamente individuos jóvenes. Objetivo: Determinar los factores de riesgo cardiovascular en adultos jóvenes mexicanos. Material y métodos: Estudio observacional, descriptivo y transversal, realizado en una muestra sana de 198 adultos jóvenes mexicanos de nivel universitario de 18 a 25 años a quienes, tras completar un cuestionario, se les evaluaron parámetros antropométricos y de tensión arterial. Se hizo un análisis comparativo de los resultados de acuerdo con el sexo y con hallazgos de otros estudios. Resultados: En el 46% de los sujetos se identificó una dieta aterogénica (predominante entre varones). El 59.1% de los individuos se clasificaron como sedentarios (en su mayoría mujeres). El 91.4% de la muestra cuenta con dos o más antecedentes heredofamiliares de ECV (y otras condiciones asociadas), siendo los más frecuentes la diabetes mellitus (71.2%), la hipertensión arterial sistémica (64.6%) y el sobrepeso u obesidad (56.6%). El 25.8% de los individuos cursó con sobrepeso (más frecuente entre mujeres). En los varones se presentó una mayor proporción de alteraciones en los niveles de tensión arterial. Conclusiones: Los hallazgos identificados con mayor frecuencia corresponden al grupo de factores de riesgo menores modificables, lo cual podría permitir el desarrollo de medidas preventivas, al tratarse de sujetos en quienes es asequible la modificación de conductas y hábitos nocivos.

El pirofosfato de tiamina reduce el daño celular inducido por hipoxia en el cerebro de ratas neonatas / Thiamine pyrophosphate reduces hypoxia-induced cellular damage in neonatal rat brain

La encefalopatía por hipoxia es causa de discapacidad y requiere de nuevas estrategias terapéuticas. El pirofosfato de tiamina (PPT) es un cofactor esencial de enzimas fundamentales en el metabolismo de la glucosa, cuya disminución puede conducir a la falla en la síntesis de ATP y a la muerte celular. El objetivo de este estudio fue determinar si la administración de PPT, puede reducir el daño celular en un modelo de hipoxia neonatal en ratas. Animales de 11 días de edad fueron tratados con PPT (130 mg/kg) en dosis única o solución salina, una hora antes del protocolo de hipoxia o al término de ésta. Los cerebros fueron colectados para la evaluación del daño celular. Además, se tomaron muestras sanguíneas para evaluar los indicadores gasométricos de presión de dióxido de carbono (PaCO2) y de oxígeno (PaO2) en sangre arterial y pH. Los resultados muestran que la administración de PPT previa a la inducción de hipoxia, reduce el daño celular y restablece los indicadores gasométricos. Estos datos indican que el uso de PPT reduce el daño inducido por la hipoxia en animales neonatos.

Hypoxic encephalopathy is a leading cause of disability and requires new therapeutic strategies. Thiamine pyrophosphate (TPP) is an essential cofactor of fundamental enzymes involved in glucose metabolism. TPP reduction may lead to ATP synthesis failure and cell death. The objective of this study was to determine if TPP administration can reduce cellular damage in a model of neonatal hypoxia in rats. Eleven day old animals were treated with TPP (130 mg/kg) as a single dose or with saline solution one hour before the hypoxia protocol or after ending the protocol. The brains were collected to evaluate cellular damage. Blood samples were also collected to evaluate arterial oxygen tension (PaO2), carbon dioxide tension (PaCO2) and acidity (pH). The results showed that TPP administration previous to hypoxia induction reduces cellular damage and reestablishes arterial blood gases. These data indicate that TPP use reduces the damage induced by hypoxia in neonatal animals.