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.

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.

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.

Medical management of the suspected victim of bioterrorism: an algorithmic approach to the undifferentiated patient.

We have purposely expanded on the well-known ATLS paradigm to aid EHCPs in their approach to a potential bioterrorism event. By building on a process that is already familiar, we hope this will aid the EHCP to remember a systematic approach to such an incident. By following this ten-step process, we believe that all EHCPs, and especially those practicing at the first echelons of care in urgent care clinics and EDs, can approach the daunting problem of biological defense with a good deal more confidence. This same model advocated for bioterrorism also may apply to natural infectious disease epidemics, particularly of emerging or re-emerging diseases, that might not be optimally managed by reliance on the conventional public health strategy that requires physician-dependent definitive diagnosis and active reporting mechanisms. The authors hope the acquired knowledge and skills one might gain will rarely be needed, but if the events surrounding the dispersal of anthrax-contaminated mail in the fall of 2001 are any indication of the future, such competencies will be invaluable.

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.

Pigtail catheters versus large-bore chest tubes for pneumothoraces in children treated in the emergency department.

OBJECTIVE: We sought to compare the efficacy (pneumothorax resolution and hospitalization days), pain (narcotic usage), and safety (need for repositioning or replacement) associated with placement of large-bore chest tubes versus pigtail catheters in children with pneumothoraces. METHODS: We conducted a retrospective chart review of all patients with pneumothoraces seen in the emergency department (ED) over a 6.5-year period who received treatment by a pediatric emergency physician with either a large-bore chest tube or a pigtail catheter. We excluded patients who had catheters placed by other specialists and patients who were endotracheally intubated. We collected the following data: complications, hospital days to discharge, and narcotic pain medications taken. RESULTS: Eleven pigtail catheters and 16 large-bore chest tubes were placed. All pneumothoraces were effectively evacuated. Three of the 11 pigtail catheters required repositioning, and one was replaced. Two of the 16 large-bore chest tubes were repositioned, and one was replaced; additionally, a pigtail catheter was added to one patient with a large-bore chest tube to facilitate evacuation of the air. Average hospital stay was similar between groups (6.2 d for pigtail catheters vs 6.8 d for large-bore chest tubes, = 0.74). Children with pigtail catheters required less narcotic pain medications than those who had large-bore chest tubes, but the differences were not significant. CONCLUSION: Pigtail catheters offer a safe and effective alternative to large-bore chest tubes for patients receiving treatment for pneumothoraces in the ED.

Ondansetron decreases vomiting associated with acute gastroenteritis: a randomized, controlled trial.

OBJECTIVE: Relatively little research has examined the role of antiemetic agents in the treatment of acute gastroenteritis. The use of the selective 5-HT3 receptor antagonists (eg, ondansetron) offers a potentially valuable treatment option. The objective of this study was to evaluate the efficacy of ondansetron for the treatment of vomiting associated with acute gastroenteritis in children. METHODS: A randomized, double blind, placebo-controlled trial was conducted in the emergency department of a tertiary-care children's hospital. Eligible patients were 1 month to 22 years old and required intravenous fluids for gastroenteritis. Of 172 patients approached, 107 were enrolled (54 to intravenous ondansetron, 53 to placebo). The mean age was 5.3 years, and 53% of the patients were male. The frequency of vomiting, admission rate, and occurrence of complications were measured. RESULTS: After drug administration, 38 (70%) of the 54 patients in the ondansetron group had complete cessation of vomiting compared with 27 (51%) of the 53 patients in the placebo group. Sixteen (30%) of the 53 patients in the placebo group required admission compared with 14 (26%) of the 54 in the ondansetron group. An analysis of previously untreated patients with a measured serum carbon dioxide > or =15 mEq/L showed that 11 (23%) of the 47 who received placebo were admitted compared with 3 (7%) of the 43 who received ondansetron. No significant complications were detected. CONCLUSIONS: Intravenous ondansetron decreases vomiting in children with gastroenteritis. In addition, ondansetron reduces the need for admission in those who are treated at an initial visit to the emergency department and have a measured serum carbon dioxide > or =15 mEq/L. The safety and low cost of this therapy suggests that ondansetron can be valuable in treating gastroenteritis in children.

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.

Computerized reminders to physicians in the emergency department: a web-based system to report late-arriving abnormal laboratory results.

Inadequate follow-up for abnormal laboratory results is a frequent cause of medical errors, especially for those that arrive after the patient is discharged in an Emergency Department (ED) setting. We have developed and implemented a computerized reminder system called the Automated Late-Arriving Results Monitoring System (ALARMS) for the Emergency Department at Children's Hospital, Boston. ALARMS scans the hospital's laboratory and ED registration databases to generate an electronic daily log of all late-arriving abnormal results for ED patients, which can be obtained by authorized physicians through a web-based user interface inside the hospital's intranet. We believe, by using this automated data-driven rule-based reminder system, we can minimize the risk of errors resulting from late-arriving laboratory data without requiring substantial additional efforts from clinicians.