Background Venezuela is one of the most violent countries in the world. According to the United Nations, homicide rates in the country increased from 32.9 to 61.9 per 100 000 people between 2000 and 2014. This upsurge coincided with a slowdown in life expectancy improvements. We estimate mortality trends and quantify the impact of violence-related deaths and other causes of death on life expectancy and lifespan inequality in Venezuela. Methods Life tables were computed with corrected age-specific mortality rates from 1996 to 2013. From these, changes in life expectancy and lifespan inequality were decomposed by age and cause of death using a continuous-change model. Lifespan inequality, or variation in age at death, is measured by the standard deviation of the age-at-death distribution. Results From 1996 to 2013 in Venezuela, female life expectancy rose 3.57 [95% confidence interval (CI): 3.08–4.09] years [from 75.79 (75.98–76.10) to 79.36 (78.97–79.68)], and lifespan inequality fell 1.03 (–2.96 to 1.26) years [from 18.44 (18.01–19.00) to 17.41 (17.30–18.27)]. Male life expectancy increased 1.64 (1.09–2.25) years [from 69.36 (68.89–59.70) to 71.00 (70.53–71.39)], but lifespan inequality increased 0.95 (–0.80 to 2.89) years [from 20.70 (20.24–21.08) to 21.65 (21.34–22.12)]. If violence-related death rates had not risen over this period, male life expectancy would have increased an additional 1.55 years, and lifespan inequality would have declined slightly (–0.31 years). Conclusions As increases in violence-related deaths among young men (ages 15–39) have slowed gains in male life expectancy and increased lifespan inequality, Venezuelan males face more uncertainty about their age at death. There is an urgent need for more accurate mortality estimates in Venezuela.
Abstractobjectives The World Health Organization (WHO) recently issued revised first-line antituberculosis (anti-TB) drug dose recommendations for children, with dose increases proposed for each drug. No pharmacokinetic data are available from South American children. We examined the need for implementation of these revised guidelines in Venezuela.methods Plasma isoniazid, rifampicin, pyrazinamide and ethambutol concentrations were assessed prior to and at 2, 4 and 8 h after intake of TB drugs by 30 TB patients aged 1-15 years. The effects of dose in mg ⁄ kg, age, sex, body weight, malnutrition and acetylator phenotype on maximum plasma drug concentrations (C max ) and exposure (AUC 0-24 ) were determined.results 25 patients (83%) had an isoniazid C max below 3 mg ⁄ l and 23 patients (77%) had a rifampicin C max below 8 mg ⁄ l. One patient (3%) had a pyrazinamide C max below 20 mg ⁄ l. The low number of patients on ethambutol (n = 5) precluded firm conclusions. C max and AUC 0-24 of all four drugs were significantly and positively correlated with age and body weight. Patients aged 1-4 years had significantly lower C max and AUC 0-24 values for isoniazid and rifampicin and a trend to lower values for pyrazinamide compared to those aged 5-15 years. The geometric mean AUC 0-24 for isoniazid was much lower in fast acetylators than in slow acetylators (5.2 vs. 12.0, P < 0.01).conclusion We provide supportive evidence for the implementation of the revised WHO pediatric TB drug dose recommendations in Venezuela. Follow-up studies are needed to describe the corresponding plasma levels that are achieved by the recommended increased doses of TB drugs.
Background Between the 1950s and 2000, Venezuela showed one of the most substantial improvements in infant mortality rates in Latin America. However, the recent economic crisis alongside an increase in infectious and parasitic diseases might be reversing previous patterns. Because no official updated mortality statistics have been published since 2013, the effect of these recent events has been difficult to assess accurately. We therefore aimed to estimate infant mortality rate trends and report the effect of the crisis. MethodsWe estimated infant mortality rates using direct methods (ie, death counts from Venezuelan Ministry of Health via yearbooks and notifiable diseases bulletins, and birth records published by the UN Economic Commission for Latin America and the Caribbean and the Venezuelan National Institute of Statistics) and indirect methods (using census data and a Living Conditions Survey ENCOVI 2016). We shaped yearly estimations using a semiparametric regression model, specifically a P-Spline model with a cubic thin plate base. The primary objective was to estimate infant mortality rate trends from 1985 to 2016. FindingsAround 2009, the long-term decline in infant mortality rate stopped, and a new pattern of increase was observed. The infant mortality rate reached 21•1 deaths per 1000 livebirths (90% CI −17•8 to 24•3) in 2016, almost 1•4 times the rate of 2008 (15•0, −14•0 to 16•1). This increase represents a huge setback on previous achievements in reducing infant mortality. Interpretation Our conservative estimation indicates that Venezuela is in the throes of a humanitarian crisis. The increase in infant mortality rate in 2016 compared with 2008 takes the country back to the level observed at the end of the 1990s, wiping out 18 years of expected progress, and leaves the Venezuelan Government far from achieving the target of nine deaths per 1000 livebirths stated in the UN Millennium Development Goals.
In Venezuelan children a clear difference in isoniazid pharmacokinetics and acetylator phenotype between genotypically slow and genotypically intermediate or rapid acetylating children was observed. Original submitted 31 July 2013; Revision submitted 11 November 2013.
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