OBJECTIVE: To determine levels and trends in the fatal and nonfatal burden of diseases and injuries among younger children (aged <5 years), older children (aged 5-9 years), and adolescents (aged 10-19 years) between 1990 and 2013 in 188 countries from the Global Burden of Disease (GBD) 2013 study.
EVIDENCE REVIEW: Data from vital registration, verbal autopsy studies, maternal and child death surveillance, and other sources covering 14,244 site-years (ie, years of cause of death data by geography) from 1980 through 2013 were used to estimate cause-specific mortality. Data from 35,620 epidemiological sources were used to estimate the prevalence of the diseases and sequelae in the GBD 2013 study. Cause-specific mortality for most causes was estimated using the Cause of Death Ensemble Model strategy. For some infectious diseases (eg, HIV infection/AIDS, measles, hepatitis B) where the disease process is complex or the cause of death data were insufficient or unavailable, we used natural history models. For most nonfatal health outcomes, DisMod-MR 2.0, a Bayesian metaregression tool, was used to meta-analyze the epidemiological data to generate prevalence estimates.
FINDINGS: Of the 7.7 (95% uncertainty interval [UI], 7.4-8.1) million deaths among children and adolescents globally in 2013, 6.28 million occurred among younger children, 0.48 million among older children, and 0.97 million among adolescents. In 2013, the leading causes of death were lower respiratory tract infections among younger children (905.059 deaths; 95% UI, 810,304-998,125), diarrheal diseases among older children (38,325 deaths; 95% UI, 30,365-47,678), and road injuries among adolescents (115,186 deaths; 95% UI, 105,185-124,870). Iron deficiency anemia was the leading cause of years lived with disability among children and adolescents, affecting 619 (95% UI, 618-621) million in 2013. Large between-country variations exist in mortality from leading causes among children and adolescents. Countries with rapid declines in all-cause mortality between 1990 and 2013 also experienced large declines in most leading causes of death, whereas countries with the slowest declines had stagnant or increasing trends in the leading causes of death. In 2013, Nigeria had a 12% global share of deaths from lower respiratory tract infections and a 38% global share of deaths from malaria. India had 33% of the world's deaths from neonatal encephalopathy. Half of the world's diarrheal deaths among children and adolescents occurred in just 5 countries: India, Democratic Republic of the Congo, Pakistan, Nigeria, and Ethiopia.
CONCLUSIONS AND RELEVANCE: Understanding the levels and trends of the leading causes of death and disability among children and adolescents is critical to guide investment and inform policies. Monitoring these trends over time is also key to understanding where interventions are having an impact. Proven interventions exist to prevent or treat the leading causes of unnecessary death and disability among children and adolescents. The findings presented here show that these are underused and give guidance to policy makers in countries where more attention is needed.
METHODS: Using HPV serology as a marker of HPV-related cancer, we examined the interaction between smoking and HPV16 in 459 oropharyngeal (and 1445 oral cavity and laryngeal) cancer patients and 3024 control participants from two large European multi-centre studies. Odds ratios and credible intervals [CrI], adjusted for potential confounders, were estimated using Bayesian logistic regression.
RESULTS: Both smoking [odds ratio (OR [CrI]: 6.82 [4.52, 10.29]) and HPV seropositivity (OR [CrI]: 235.69 [99.95, 555.74]) were independently associated with oropharyngeal cancer. The joint association of smoking and HPV seropositivity was consistent with that expected on the additive scale (synergy index [CrI]: 1.32 [0.51, 3.45]), suggesting they act as independent risk factors for oropharyngeal cancer.
CONCLUSIONS: Smoking was consistently associated with increase in oropharyngeal cancer risk in models stratified by HPV16 seropositivity. In addition, we report that the prevalence of oropharyngeal cancer increases with smoking for both HPV16-positive and HPV16-negative persons. The impact of smoking on HPV16-positive oropharyngeal cancer highlights the continued need for smoking cessation programmes for primary prevention of head and neck cancer.
METHODS: The warfarin maintenance doses for 140 patients were predicted using the dosing tool and compared with the observed maintenance dose. The impact of genotype was assessed by predicting maintenance doses with prior parameter values known to be altered by genetic variability (eg, EC50 for VKORC1 genotype). The prior population was evaluated by fitting the published kinetic-pharmacodynamic model, which underpins the Bayesian tool, to the observed data using NONMEM and comparing the model parameter estimates with published values.
RESULTS: The Bayesian tool produced positively biased dose predictions in the new cohort of patients (mean prediction error [95% confidence interval]; 0.32 mg/d [0.14-0.5]). The bias was only observed in patients requiring ≥7 mg/d. The direction and magnitude of the observed bias was not influenced by genotype. The prior model provided a good fit to our data, which suggests that the bias was not caused by different prior and posterior populations.
CONCLUSIONS: Maintenance doses for patients requiring ≥7 mg/d were overpredicted. The bias was not due to the influence of genotype nor was it related to differences between the prior and posterior populations. There is a need for a more mechanistic model that captures warfarin dose-response relationship at higher warfarin doses.