BACKGROUND AND OBJECTIVES: Nontherapeutic medication ingestions continue to be a major pediatric health problem, with recent increases in ingestions despite a number of public health interventions. It is unknown how changes in adult prescription drug use relate to pediatric medication poisonings. The objective of the study was to measure the association between changing adult prescription drug patterns and pediatric medication exposures and poisonings and identify high-risk classes of medications and pediatric age groups. METHODS: We measured monthly pediatric exposures and poisonings using the National Poison Data System and prescriptions written for adults using the National Ambulatory Medical Care Surveys for 2000 through 2009. Associations between adult prescriptions for oral hypoglycemics, antihyperlipidemics, beta-blockers, and opioids and exposures and poisonings among children 0 to 5, 6 to 12, and 13 to 19 years were analyzed by using multiple time-series analysis. Emergency department visits, serious injuries, and hospitalizations stemming from these associations were described. RESULTS: Adult medication prescriptions were statistically significantly associated with exposures and poisonings in children of all ages, with the strongest association observed for opioids. Across medications, the greatest risk was among children 0 to 5 years old, followed by 13- to 19-year-olds. Rates of emergency department visits were highest for events related to hypoglycemics (60.1%) and beta-blockers (59.7%), whereas serious injuries and hospitalizations occurred most frequently with opioids (26.8% and 35.2%, respectively) and hypoglycemics (19.5% and 49.4%, respectively). CONCLUSIONS: Increasing adult drug prescriptions are strongly associated with rising pediatric exposures and poisonings, particularly for opioids and among children 0 to 5 years old. These associations have sizable impacts, including high rates of serious injury and health care use.

Although it is well established that funding source influences the publication of clinical trials, relatively little is known about how funding influences trial design. We examined a public trial registry to determine how funding source shapes trial design among trials involving antihyperlipidemics. We used an automated process to identify and analyze 809 trials from a set of 72,564. Three networks representing industry-, collaboratively, and non-industry-funded trials were constructed. Each network comprised 18 drugs as nodes connected according to the number of comparisons made between them. The results indicated that industry-funded trials were more likely to compare across drugs and examine dyslipidemia as a condition, and less likely to register safety outcomes. The source of funding for clinical trials had a measurable effect on trial design, which helps quantify differences in research agendas. Improved monitoring of current clinical trials may be used to more closely align research agendas to clinical needs.

BACKGROUND: The $1.1 billion investment in comparative effectiveness research will reshape the evidence-base supporting decisions about treatment effectiveness, safety, and cost. Defining the current prevalence and characteristics of comparative effectiveness (CE) research will enable future assessments of the impact of this program. METHODS: We conducted an observational study of clinical trials addressing priority research topics defined by the Institute of Medicine and conducted in the US between 2007 and 2010. Trials were identified in ClinicalTrials.gov. Main outcome measures were the prevalence of comparative effectiveness research, nature of comparators selected, funding sources, and impact of these factors on results. RESULTS: 231 (22.3%; 95% CI 19.8%-24.9%) studies were CE studies and 804 (77.7%; 95% CI, 75.1%-80.2%) were non-CE studies, with 379 (36.6%; 95% CI, 33.7%-39.6%) employing a placebo control and 425 (41.1%; 95% CI, 38.1%-44.1%) no control. The most common treatments examined in CE studies were drug interventions (37.2%), behavioral interventions (28.6%), and procedures (15.6%). Study findings were favorable for the experimental treatment in 34.8% of CE studies and greater than twice as many (78.6%) non-CE studies (P0.001). CE studies were more likely to receive government funding (P = 0.003) and less likely to receive industry funding (P = 0.01), with 71.8% of CE studies primarily funded by a noncommercial source. The types of interventions studied differed based on funding source, with 95.4% of industry trials studying a drug or device. In addition, industry-funded CE studies were associated with the fewest pediatric subjects (P0.001), the largest anticipated sample size (P0.001), and the shortest study duration (P0.001). CONCLUSIONS: In this sample of studies examining high priority areas for CE research, less than a quarter are CE studies and the majority is supported by government and nonprofits. The low prevalence of CE research exists across CE studies with a broad array of interventions and characteristics.

BACKGROUND AND OBJECTIVE: Optimal treatment decisions in children require sufficient evidence on the safety and efficacy of pharmaceuticals in pediatric patients. However, there is concern that not enough trials are conducted in children and that pediatric trials differ from those performed in adults. Our objective was to measure the prevalence of pediatric studies among clinical drug trials and compare trial characteristics and quality indicators between pediatric and adult drug trials. METHODS: For conditions representing a high burden of pediatric disease, we identified all drug trials registered in ClinicalTrials.gov with start dates between 2006 and 2011 and tracked the resulting publications. We measured the proportion of pediatric trials and subjects for each condition and compared pediatric and adult trial characteristics and quality indicators. RESULTS: For the conditions selected, 59.9% of the disease burden was attributable to children, but only 12.0% (292/2440) of trials were pediatric (P .001). Among pediatric trials, 58.6% were conducted without industry funding compared with 35.0% of adult trials (P .001). Fewer pediatric compared with adult randomized trials examined safety outcomes (10.1% vs 16.9%, P = .008). Pediatric randomized trials were slightly more likely to be appropriately registered before study start (46.9% vs 39.3%, P = .04) and had a modestly higher probability of publication in the examined time frame (32.8% vs 23.2%, P = .04). CONCLUSIONS: There is substantial discrepancy between pediatric burden of disease and the amount of clinical trial research devoted to pediatric populations. This may be related in part to trial funding, with pediatric trials relying primarily on government and nonprofit organizations.

OBJECTIVES: The objectives were to identify patient and hospital characteristics associated with the use of computed tomography (CT) imaging of the cervical spine (c-spine) in the evaluation of injured children and, in particular, to examine the influence of hospital setting. METHODS: This was a retrospective cohort of children younger than 19 years of age from the Massachusetts Hospital Emergency Department (ED) database who were discharged from the ED with an injury diagnosis from 2005 through 2009. Multivariable logistic regression was used to analyze characteristics associated with CT imaging of the c-spine. RESULTS: Of the 929,626 pediatric patients diagnosed with an injury in Massachusetts EDs and then discharged home, 1.3% underwent CT imaging of the c-spine. Rates of CT imaging nearly doubled over the 5 years. In the multivariable model, patient age (adjusted odds ratio [AOR] = 2.3, 95% confidence interval [CI] = 2.0 to 2.7 for children age 12 to 18 years vs. under 1 year of age) and evaluation outside of a pediatric Level I trauma center (AOR = 2.2, 95% CI = 1.1 to 4.3 for children evaluated at non Level I trauma centers vs. pediatric Level I trauma centers; AOR = 2.1, 95% CI = 0.93 to 4.7 for children evaluated at adult Level I trauma centers vs. pediatric Level I trauma centers) were associated with higher rates of CT imaging of the c-spine. CONCLUSIONS: Cervical spine CT imaging for children discharged from the ED with trauma diagnoses increased from 2005 through 2009. Older age and evaluation outside a Level I pediatric trauma center were associated with a higher c-spine CT rate. Educational interventions focused outside pediatric trauma centers may be an effective approach to decreasing CT imaging of the c-spine of pediatric trauma patients.

OBJECTIVES: The objective was to identify patient, provider, and hospital characteristics associated with the use of neuroimaging in the evaluation of head trauma in children. METHODS: This was a cross-sectional study of children ( or =19 years of age) with head injuries from the National Hospital Ambulatory Medical Care Survey (NHAMCS) collected by the National Center for Health Statistics. NHAMCS collects data on approximately 25,000 visits annually to 600 randomly selected hospital emergency and outpatient departments. This study examined visits to U.S. emergency departments (EDs) between 2002 and 2006. Multivariable logistic regression was used to analyze characteristics associated with neuroimaging in children with head injuries. RESULTS: There were 50,835 pediatric visits in the 5-year sample, of which 1,256 (2.5%, 95% confidence interval [CI] = 2.2% to 2.7%) were for head injury. Among these, 39% (95% CI = 34% to 43%) underwent evaluation with neuroimaging. In multivariable analyses, factors associated with neuroimaging included white race (odds ratio [OR] = 1.5, 95% CI = 1.02 to 2.1), older age (OR = 1.3, 95% CI = 1.1 to 1.5), presentation to a general hospital (vs. a pediatric hospital, OR = 2.4, 95% CI = 1.1 to 5.3), more emergent triage status (OR = 1.4, 95% CI = 1.1 to 1.8), admission or transfer (OR = 2.7, 95% CI = 1.4 to 5.3), and treatment by an attending physician (OR = 2.0, 95% CI = 1.1 to 3.7). The effect of race was mitigated at the pediatric hospitals compared to at the general hospitals (p 0.001). CONCLUSIONS: In this study, patient race, age, and hospital-specific characteristics were associated with the frequency of neuroimaging in the evaluation of children with closed head injuries. Based on these results, focusing quality improvement initiatives on physicians at general hospitals may be an effective approach to decreasing rates of neuroimaging after pediatric head trauma.

PURPOSE: Adverse drug events (ADEs) are a common complication of medical care resulting in high morbidity and medical expenditure. Population level estimates of outpatient ADEs are limited. Our objective was to provide national estimates and characterizations of outpatient ADEs and determine risk factors associated with these events. METHODS: Data are from the National Center for Health Statistics which collects information on patient visits to outpatient clinics and emergency departments throughout the United States. We examined visits between 1995 and 2005 and measured the national annual estimates of and risk factors for outpatient ADEs requiring medical treatment. RESULTS: The national annual number of ADE-related visits was 4 335,990 (95%CI: 4 326 872-4 345 108). Visits for ADEs to outpatient clinics increased over the study period from 9.0 to 17.0 per 1000 persons (p-value for trend 0.001). In multivariate analyses, factors associated with ADE visits included patient age (OR: 2.13; 95%CI: 1.63-2.79 for 65 years and older), number of medications taken by patient (OR: 1.88; 95%CI: 1.58-2.25 for five medications or more), and female gender (OR: 1.51; 95%CI: 1.34-1.71). Overall, outpatient ADEs resulted in 107,468 (95%CI: 89 011-125 925) hospital admissions annually, with older patients at highest risk for hospitalization (p-value for trend 0.001). CONCLUSIONS: Both patient age and polypharmacy use are risk factors for ADE-related healthcare visits, which have substantially increased in outpatient clinics between 1995 and 2005. The incidence of ADEs has particularly increased among patients 65 years and older with as many as 1 in 20 persons seeking medical care for an ADE.

BACKGROUND: Clinical trial registries are in widespread use to promote transparency around trials and their results. OBJECTIVE: To describe characteristics of drug trials listed in ClinicalTrials.gov and examine whether the funding source of these trials is associated with favorable published outcomes. DESIGN: An observational study of safety and efficacy trials for anticholesteremics, antidepressants, antipsychotics, proton-pump inhibitors, and vasodilators conducted between 2000 and 2006. SETTING: ClinicalTrials.gov, a Web-based registry of clinical trials launched in 1999. MEASUREMENTS: Publications resulting from the trials for the 5 drug categories of interest were identified, and data were abstracted on the trial record and publication, including timing of registration, elements of the study design, funding source, publication date, and study outcomes. Assessments were based on the primary funding categories of industry, government agencies, and nonprofit or nonfederal organizations. RESULTS: Among 546 drug trials, 346 (63%) were primarily funded by industry, 74 (14%) by government sources, and 126 (23%) by nonprofit or nonfederal organizations. Trials funded by industry were more likely to be phase 3 or 4 trials (88.7%; P 0.001 across groups), to use an active comparator in controlled trials (36.8%; P = 0.010 across groups), to be multicenter (89.0%; P 0.001 across groups), and to enroll more participants (median sample size, 306 participants; P 0.001 across groups). Overall, 362 (66.3%) trials had published results. Industry-funded trials reported positive outcomes in 85.4% of publications, compared with 50.0% for government-funded trials and 71.9% for nonprofit or nonfederal organization-funded trials (P 0.001). Trials funded by nonprofit or nonfederal sources with industry contributions were also more likely to report positive outcomes than those without industry funding (85.0% vs. 61.2%; P = 0.013). Rates of trial publication within 24 months of study completion ranged from 32.4% among industry-funded trials to 56.2% among nonprofit or nonfederal organization-funded trials without industry contributions (P = 0.005 across groups). LIMITATIONS: The publication status of a trial could not always be confirmed, which could result in misclassification. Additional information on study protocols and comprehensive trial results were not available to further explore underlying factors for the association between funding source and outcome reporting. CONCLUSION: In this sample of registered drug trials, those funded by industry were less likely to be published within 2 years of study completion and were more likely to report positive outcomes than were trials funded by other sources. PRIMARY FUNDING SOURCE: National Library of Medicine and National Institute of Child Health and Human Development, National Institutes of Health.

OBJECTIVE: We measured the relative impact of influenza and respiratory syncytial virus (RSV) infections in young children in terms of emergency department (ED) visits, clinical care requirements, and overall resource use. METHODS: Patients who were aged