Rationale: Limited data exist about the international burden of severe sepsis in critically ill children.Objectives: To characterize the global prevalence, therapies, and outcomes of severe sepsis in pediatric intensive care units to better inform interventional trials.Methods: A point prevalence study was conducted on 5 days throughout 2013-2014 at 128 sites in 26 countries. Patients younger than 18 years of age with severe sepsis as defined by consensus criteria were included. Outcomes were severe sepsis point prevalence, therapies used, new or progressive multiorgan dysfunction, ventilator-and vasoactive-free days at Day 28, functional status, and mortality.Measurements and Main Results: Of 6,925 patients screened, 569 had severe sepsis (prevalence, 8.2%; 95% confidence interval, 7.6-8.9%). The patients' median age was 3.0 (interquartile range [IQR], 0.7-11.0) years. The most frequent sites of infection were respiratory (40%) and bloodstream (19%). Common therapies included mechanical ventilation (74% of patients), vasoactive infusions (55%), and corticosteroids (45%). Hospital mortality was 25% and did not differ by age or between developed and resourcelimited countries. Median ventilator-free days were 16 (IQR, 0-25), and vasoactive-free days were 23 (IQR,(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28). Sixty-seven percent of patients had multiorgan dysfunction at sepsis recognition, with 30% subsequently developing new or progressive multiorgan dysfunction. Among survivors, 17% developed at least moderate disability. Sample sizes needed to detect a 5-10% absolute risk reduction in outcomes within interventional trials are estimated between 165 and 1,437 patients per group.Conclusions: Pediatric severe sepsis remains a burdensome public health problem, with prevalence, morbidity, and mortality rates similar to those reported in critically ill adult populations. International clinical trials targeting children with severe sepsis are warranted.
C&RT is a promising research tool for the identification of at-risk populations in public health research and outreach.
Drop-out is a prevalent complication in the analysis of data from longitudinal studies, and remains an active area of research for statisticians and other quantitative methodologists. This tutorial is designed to synthesize and illustrate the broad array of techniques that are used to address outcome-related drop-out, with emphasis on regression-based methods. We begin with a review of important assumptions underlying likelihood-based and semi-parametric models, followed by an overview of models and methods used to draw inferences from incomplete longitudinal data. The majority of the tutorial is devoted to detailed analysis of two studies with substantial rates of drop-out, designed to illustrate the use of effective methods that are relatively easy to apply: in the first example, we use both semi-parametric and fully parametric models to analyse repeated binary responses from a clinical trial of smoking cessation interventions; in the second, pattern mixture models are used to analyse longitudinal CD4 counts from an observational cohort study of HIV-infected women. In each example, we describe exploratory analyses, model formulation, estimation methodology and interpretation of results. Analyses of incomplete data requires making unverifiable assumptions, and these are discussed in detail within the context of each application. Relevant SAS code is provided.
The aim was to estimate lifetime sex and age-specific incidence of migraine. Data are from the American Migraine Prevalence and Prevention study, a mailed survey sent to 120,000 US households. Age-specific incidence was estimated using self-reported data relevant to identification of migraine cases, age of onset of migraine and age at interview. Migraine incidence peaked between the ages of 20 and 24 years in women (18.2/1000 person-years) and the ages of 15 and 19 years in men (6.2/1000 person-years). Cumulative incidence was 43% in women and 18% in men. Median age of onset was 25 years among women and 24 years among men. Onset in 50% of cases occurred before age 25 and in 75% before age 35 years. Four of every 10 women and two of every 10 men will contract migraine in their lifetime, most before age 35 years. The incidence estimates from this analysis are consistent with those reported in previous longitudinal studies.
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