The Genomics Research and Innovation Network: creating an interoperable, federated, genomics learning system.

PURPOSE: Clinicians and researchers must contextualize a patient's genetic variants against population-based references with detailed phenotyping. We sought to establish globally scalable technology, policy, and procedures for sharing biosamples and associated genomic and phenotypic data on broadly consented cohorts, across sites of care. METHODS: Three of the nation's leading children's hospitals launched the Genomic Research and Innovation Network (GRIN), with federated information technology infrastructure, harmonized biobanking protocols, and material transfer agreements. Pilot studies in epilepsy and short stature were completed to design and test the collaboration model. RESULTS: Harmonized, broadly consented institutional review board (IRB) protocols were approved and used for biobank enrollment, creating ever-expanding, compatible biobanks. An open source federated query infrastructure was established over genotype-phenotype databases at the three hospitals. Investigators securely access the GRIN platform for prep to research queries, receiving aggregate counts of patients with particular phenotypes or genotypes in each biobank. With proper approvals, de-identified data is exported to a shared analytic workspace. Investigators at all sites enthusiastically collaborated on the pilot studies, resulting in multiple publications. Investigators have also begun to successfully utilize the infrastructure for grant applications. CONCLUSIONS: The GRIN collaboration establishes the technology, policy, and procedures for a scalable genomic research network.

Correction: The Genomics Research and Innovation Network: creating an interoperable, federated, genomics learning system.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Factors associated with the use of cervical spine computed tomography imaging in pediatric trauma patients.

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.

A randomized clinical trial of the management of esophageal coins in children.

CONTEXT: Children frequently ingest coins. When lodged in the esophagus, the coin may cause complications and must either be removed or observed to pass spontaneously. OBJECTIVES: (1) To compare relatively immediate endoscopic removal to a period of observation followed by removal when necessary and (2) to evaluate the relationship between select clinical features and spontaneous passage. DESIGN/SETTING: Randomized, prospective study of children <21 years old who presented to an emergency department with esophageal coins in the esophagus. Exclusion criteria were (1) history of tracheal or esophageal surgery, (2) showing symptoms, or (3) swallowing the coin >24 hours earlier. Children were randomized to either endoscopic removal (surgery) or admission for observation, with repeat radiographs approximately 16 hours after the initial image. OUTCOME MEASURES: Proportion of patients requiring endoscopic removal, length of hospital stay, and the number of complications observed. RESULTS: Among 168 children who presented with esophageal coins lodged in the esophagus, 81 were eligible. Of those eligible, 60 enrolled, 20 refused consent, and 1 was not approached. In the observation group, 23 of 30 (77%) children required endoscopy compared with 21 of 30 (70%) in the surgical group. Total hospital length of stay was longer in the randomized-to-observation group compared with the randomized-to-surgery group (mean: 19.4 [SD: +/-8.0] hours vs 10.7 [SD: +/-7.1] hours, respectively). There were no complications in either group. Spontaneous passage occurred at similar rates in both groups (23% vs 30%). Spontaneous passage was more likely in older patients (66 vs 46 months) and male patients (odds ratio: 3.7; 95% confidence interval: 0.98-13.99) and more likely to occur when the coin was in the distal one third of the esophagus (56% vs 27% [95% confidence interval: 1.07-5.57]). CONCLUSIONS: Because 25% to 30% of esophageal coins in children will pass spontaneously without complications, treatment of these patients may reasonably include a period of observation, in the range of 8 to 16 hours, particularly among older children and those with distally located coins.

When body temperature changes, does rectal temperature lag?

By using temporal artery and rectal thermometers, we followed temperatures in 45 febrile (>38.5 degrees C) infants given an antipyretic drug. Sixty and 90 minutes after drug administration, temporal artery temperatures had decreased significantly more than rectal temperatures. When body arterial temperature changes rapidly, changes in rectal temperature may lag.

Efficacy of an educational Web site for educating physicians about bioterrorism.

OBJECTIVES: To determine whether a Web-based educational intervention improves emergency physicians' knowledge about bioterrorism and to survey physicians' knowledge and sources of information on bioterrorism. METHODS: Prospective randomized controlled trial using pre- and postintervention testing in hospitals. Participants were general and pediatric emergency medicine attending physicians, fellows, and fourth-year emergency medicine residents. All participants completed a pretest and attended a lecture on bioterrorism. Participants were then randomized to the Web intervention group that received continuous access to a bioterrorism educational Web site with weekly exposure to case scenarios of diseases due to biological agents, or the control group. Participants were retested after one and six months and surveyed to identify their sources of information and assess their knowledge. RESULTS: Sixty-three physicians completed the pretest. There was no difference in mean +/- standard deviation (SD) pretest scores between Web intervention (45% +/- 10%) and control (44% +/- 10%) groups (mean difference: 1.9%; 95% confidence interval [CI] = -6.7% to 2.9%). There was no significant difference between pre- and posttest scores among groups at one month (Web intervention 48% +/- 10% vs. control 45% +/- 10%; mean difference: 3.3%; 95% CI = -8.5% to 2.0%) and six months (Web intervention 51% +/- 8% vs. control 47% +/- 9%; mean difference: 3.8%; 95% CI = -8.8% to 1.2%). More than 60% of physicians cited media reports as their primary source of information on bioterrorism and believed that their knowledge of bioterrorism was limited after one month. CONCLUSIONS: Providing physicians information on bioterrorism through simulated cases and continuous access to an educational Web site does not increase knowledge of bioterrorism. Physicians are more likely to use media reports for their primary source of information.

Is it influenza or anthrax? A decision analytic approach to the treatment of patients with influenza-like illnesses.

STUDY OBJECTIVE: We analyze the risks and benefits of alternative treatment strategies for non-septic-appearing febrile patients with influenza-like illnesses and possible exposure to anthrax. METHODS: We used a decision analytic model to evaluate 6 testing and treatment strategies in an emergency department. Patients were non-septic-appearing and had influenza-like illnesses but low likelihood of exposure to anthrax. The following interventions were used: (1) no empiric antibiotics; (2) blood culture and treatment only if the result was positive; (3) rapid testing for influenza and, for those who tested negative, treatment with 60 days of ciprofloxacin; (4) a two-test strategy in which all patients were first tested for influenza; those who tested negative had a blood culture test and were treated empirically with ciprofloxacin for 3 days while waiting for blood culture results; (5) culture test for all patients and treatment with ciprofloxacin for up to 3 days while waiting for blood culture results; and (6) treatment of all patients with ciprofloxacin empirically for 60 days. Main outcome measures were deaths, complications from anthrax, adverse events from ciprofloxacin, and ciprofloxacin patient-days. RESULTS: For nonzero probabilities of anthrax, patient mortality was always lowest in the strategies in which all patients were treated empirically for anthrax either for 60 days or for 3 days pending blood culture results. These strategies, however, were associated with more morbidity (more ciprofloxacin patient-days and more antibiotic adverse events) than were strategies without empiric treatment. The numbers of adverse events and antibiotic patient-days were reduced substantially with the two-test strategy, in which patients with influenza were identified early and not treated. In general, for probabilities of anthrax equaling or exceeding 2%, treating all patients empirically for 60 days was best, but for probabilities between 0.1% and 2%, the sensitivity of blood culture for anthrax determined the optimal strategy: when the sensitivity exceeded 95%, a short course of empiric ciprofloxacin until blood culture results became available was best, but for sensitivities below 95%, more aggressive empiric antibiotics use was warranted. The proportion of patients with influenza in the community affected the choice of strategy, so that seasonal variation exists. CONCLUSION: During influenza season, our findings support rapid testing for influenza, followed by empiric treatment for anthrax pending blood culture results for those who test negative for influenza. Our results help to highlight the importance of developing rapid and sensitive tests for anthrax and of developing improved surveillance and methods to calculate the previous probability of attacks.

Development of a model of focal pneumococcal pneumonia in young rats.

BACKGROUND: A recently licensed pneumococcal conjugate vaccine has been shown to be highly effective in the prevention of bacteremia in immunized children but the degree of protection against pneumonia has been difficult to determine. METHODS: We sought to develop a model of Streptococcus pneumoniae pneumonia in Sprague-Dawley rats. We challenged three-week old Sprague-Dawley pups via intrapulmonary injection of S. pneumoniae serotypes 3 and 6B. Outcomes included bacteremia, mortality as well histologic sections of the lungs. RESULTS: Pneumonia was reliably produced in animals receiving either 10 or 100 cfu of type 3 pneumococci, with 30% and 50% mortality respectively. Similarly, with type 6B, the likelihood of pneumonia increased with the inoculum, as did the mortality rate. Prophylactic administration of a preparation of high-titered anticapsular antibody prevented the development of type 3 pneumonia and death. CONCLUSION: We propose that this model may be useful for the evaluation of vaccines for the prevention of pneumococcal pneumonia.

Disseminated varicella infection due to the vaccine strain of varicella-zoster virus, in a patient with a novel deficiency in natural killer T cells.

An 11-year-old girl presented with a papulovesicular rash and severe respiratory distress 5 weeks after receiving varicella vaccine. Restriction fragment length-polymorphism analysis of virus isolated from an endotracheal-tube aspirate and from bronchoalveolar lavage revealed that this patient's illness was due to the Oka vaccine strain of varicella. An extensive immunologic analysis failed to identify a known diagnostic entity to explain her susceptibility to this attenuated vaccine strain. Analysis of her lymphocytes on separate occasions, months after recovery from her illness, revealed a profound deficiency of natural killer T (NKT) cells and of NKT-cell activity, suggesting that NKT cells contribute to host defense against varicella virus.

The value of parental report for diagnosis and management of dehydration in the emergency department.

STUDY OBJECTIVES: We define the predictive value of parents' computer-based report for history and physical signs of dehydration for a primary outcome of percentage of dehydration (fluid deficit) and 2 secondary outcomes: clinically important acidosis and hospital admission. We also sought to compare the reports of physical signs related to dehydration made by parents and nurses. METHODS: We performed a prospective observational trial in an urban pediatric emergency department. A convenience sample of parents completed a computer-based interview covering historical details and physical signs (ill appearance, sunken fontanelle, sunken eyes, decreased tears, dry mouth, cool extremities, and weak cry) related to dehydration. Nurses independently completed an assessment of physical signs for enrolled children. The primary outcome was the degree of dehydration (fluid deficit), which was defined as the percentage difference between initial ED weight and stable final weight after the illness. Secondary outcomes included clinically important acidosis (defined as a serum CO(2) value of

Computerized recruiting for clinical trials in real time.

STUDY OBJECTIVE: Success of prospective studies, particularly in the emergency department, often depends on immediate identification of eligible patients to ensure timely sample collection and initiation of study interventions. We report use of a real-time automated notification system to identify potential patients for a clinical trial at the time of ED registration on the basis of information routinely collected. We hypothesize that the automated notification system improves the rate of investigator notification. METHODS: We performed a prospective comparison of the notification rate by the automated notification system compared with that by ED clinicians. RESULTS: In the 11 months before use of the automated notification system, the investigator was notified by ED staff for 56% of 61 potentially eligible patients. During 10 months of using the automated notification system, the investigator was paged by the automated notification system for 84% of 49 potentially eligible patients. CONCLUSION: The automated notification system improves study investigator notification. Use requires online linked registration, a database, and paging systems. The automated notification system is a potentially valuable tool in the recruitment of patients for clinical trials.