Current efforts to detect covert bioterrorist attacks from increases in hospital visit rates are plagued by the unpredictable nature of these rates. Although many current systems evaluate hospital visit data 1 day at a time, we investigate evaluating multiple days at once to lessen the effects of this unpredictability and to improve both the timeliness and sensitivity of detection. To test this approach, we introduce simulated disease outbreaks of varying shapes, magnitudes, and durations into 10 years of historical daily visit data from a major tertiary-care metropolitan teaching hospital. We then investigate the effectiveness of using multiday temporal filters for detecting these simulated outbreaks within the noisy environment of the historical visit data. Our results show that compared with the standard 1-day approach, the multiday detection approach significantly increases detection sensitivity and decreases latency while maintaining a high specificity. We conclude that current biosurveillance systems should incorporate a wider temporal context to improve their effectiveness. Furthermore, for increased robustness and performance, hybrid systems should be developed to capitalize on the complementary strengths of different types of temporal filters.

OBJECTIVE: To improve identification of pertussis cases by developing a decision model that incorporates recent, local, population-level disease incidence. DESIGN: Retrospective cohort analysis of 443 infants tested for pertussis (2003-7). MEASUREMENTS: Three models (based on clinical data only, local disease incidence only, and a combination of clinical data and local disease incidence) to predict pertussis positivity were created with demographic, historical, physical exam, and state-wide pertussis data. Models were compared using sensitivity, specificity, area under the receiver-operating characteristics (ROC) curve (AUC), and related metrics. RESULTS: The model using only clinical data included cyanosis, cough for 1 week, and absence of fever, and was 89% sensitive (95% CI 79 to 99), 27% specific (95% CI 22 to 32) with an area under the ROC curve of 0.80. The model using only local incidence data performed best when the proportion positive of pertussis cultures in the region exceeded 10% in the 8-14 days prior to the infant's associated visit, achieving 13% sensitivity, 53% specificity, and AUC 0.65. The combined model, built with patient-derived variables and local incidence data, included cyanosis, cough for 1 week, and the variable indicating that the proportion positive of pertussis cultures in the region exceeded 10% 8-14 days prior to the infant's associated visit. This model was 100% sensitive (p0.04, 95% CI 92 to 100), 38% specific (p0.001, 95% CI 33 to 43), with AUC 0.82. CONCLUSIONS: Incorporating recent, local population-level disease incidence improved the ability of a decision model to correctly identify infants with pertussis. Our findings support fostering bidirectional exchange between public health and clinical practice, and validate a method for integrating large-scale public health datasets with rich clinical data to improve decision-making and public health.

OBJECTIVES: (1) To determine the value of emergency department chief complaint (CC) and International Classification of Disease diagnostic codes for identifying respiratory illness in a pediatric population and (2) to modify standard respiratory CC and diagnostic code sets to better identify respiratory illness in children. RESULTS: We determined the sensitivity and specificity of CC and diagnostic codes by comparing code groups with a criterion standard. CC and diagnostic codes for 500 pediatric emergency department patients were retrospectively classified as respiratory or nonrespiratory. Respiratory diagnostic codes were further classified as upper or lower respiratory. The criterion standard was a blinded, reviewer-assigned illness category based on history, physical examination, test results, and treatment. We also modified our respiratory code sets to better identify respiratory illness in this population. METHODS: Four hundred ninety-six charts met inclusion criteria. By the criterion standard, 87 (18%) patients had upper and 47 (10%) had lower respiratory illness. The specificity of CC and diagnostic codes groups was >0.97 [95% confidence interval (CI) 0.95-0.98]. The code group sensitivities were as follows: CC was 0.47 (95% CI 0.38-0.55), upper respiratory diagnostic was 0.56 (95% CI 0.45-0.67), lower respiratory diagnostic was 0.87 (95% CI 0.74-0.95), and combined CC and/or diagnostic was 0.72 (95% CI 0.63-0.79). Modifying the respiratory code sets to better identify respiratory illness increased sensitivity but decreased specificity. CONCLUSIONS: Diagnostic and CC codes have substantial value for emergency department syndromic surveillance. Adapting our respiratory code sets to a pediatric population forced a tradeoff between sensitivity and specificity.

BACKGROUND: Emergency department (ED) based syndromic surveillance systems identify abnormally high visit rates that may be an early signal of a bioterrorist attack. For example, an anthrax outbreak might first be detectable as an unusual increase in the number of patients reporting to the ED with respiratory symptoms. Reliably identifying these abnormal visit patterns requires a good understanding of the normal patterns of healthcare usage. Unfortunately, systematic methods for determining the expected number of (ED) visits on a particular day have not yet been well established. We present here a generalized methodology for developing models of expected ED visit rates. METHODS: Using time-series methods, we developed robust models of ED utilization for the purpose of defining expected visit rates. The models were based on nearly a decade of historical data at a major metropolitan academic, tertiary care pediatric emergency department. The historical data were fit using trimmed-mean seasonal models, and additional models were fit with autoregressive integrated moving average (ARIMA) residuals to account for recent trends in the data. The detection capabilities of the model were tested with simulated outbreaks. RESULTS: Models were built both for overall visits and for respiratory-related visits, classified according to the chief complaint recorded at the beginning of each visit. The mean absolute percentage error of the ARIMA models was 9.37% for overall visits and 27.54% for respiratory visits. A simple detection system based on the ARIMA model of overall visits was able to detect 7-day-long simulated outbreaks of 30 visits per day with 100% sensitivity and 97% specificity. Sensitivity decreased with outbreak size, dropping to 94% for outbreaks of 20 visits per day, and 57% for 10 visits per day, all while maintaining a 97% benchmark specificity. CONCLUSIONS: Time series methods applied to historical ED utilization data are an important tool for syndromic surveillance. Accurate forecasting of emergency department total utilization as well as the rates of particular syndromes is possible. The multiple models in the system account for both long-term and recent trends, and an integrated alarms strategy combining these two perspectives may provide a more complete picture to public health authorities. The systematic methodology described here can be generalized to other healthcare settings to develop automated surveillance systems capable of detecting anomalies in disease patterns and healthcare utilization.

STUDY OBJECTIVE: Data used by syndromic surveillance systems must be grouped into syndromes or prodromes. Previous studies have examined the accuracy of different methods of syndromic grouping. We seek to study the effects of different syndrome grouping methods on model accuracy, a key factor in the outbreak-detection performance of syndromic surveillance systems. METHODS: Daily emergency department visit rates were analyzed from 2 urban academic tertiary care hospitals for 1,680 consecutive days. During this period, each hospital census totaled approximately 230,000 patient visits. Three methods were used to group the visits into a respiratory-related syndrome category: 1 relying on chief complaint, 1 on diagnostic codes, and 1 on a combination of the two. The different groupings of the syndromic data resulting from these methods were used to build different historical models that were then tested for forecasting accuracy and for sensitivity to detecting simulated outbreaks. RESULTS: For both hospitals, the data grouped according to chief complaints alone yielded the lowest model accuracy and the lowest detection sensitivity. Using diagnostic codes to group the data yielded better results in accuracy and sensitivity. Combining the 2 grouping methods yielded the best results in accuracy and sensitivity. Temporal smoothing of the data was shown to improve sensitivity in all cases, although to various degrees in the different models. CONCLUSION: The methods used to group input data into syndromic categories can have substantial effects on the overall performance of syndromic surveillance systems. The results suggest that incorporating diagnostic data into these systems can improve the modeling accuracy and its detection sensitivity. Furthermore, the best results may be achieved by using a combination of methods to group visits into syndromic categories.

Studies of the neural correlates of short-term memory in a wide variety of brain areas have found that transient inputs can cause persistent changes in rates of action potential firing, through a mechanism that remains unknown. In a premotor area that is responsible for holding the eyes still during fixation, persistent neural firing encodes the angular position of the eyes in a characteristic manner: below a threshold position the neuron is silent, and above it the firing rate is linearly related to position. Both the threshold and linear slope vary from neuron to neuron. We have reproduced this behavior in a biophysically plausible network model. Persistence depends on precise tuning of the strength of synaptic feedback, and a relatively long synaptic time constant improves the robustness to mistuning.

OBJECTIVE: This study sought to define a scalable architecture to support the National Health Information Network (NHIN). This architecture must concurrently support a wide range of public health, research, and clinical care activities. STUDY DESIGN: The architecture fulfils five desiderata: (1) adopt a distributed approach to data storage to protect privacy, (2) enable strong institutional autonomy to engender participation, (3) provide oversight and transparency to ensure patient trust, (4) allow variable levels of access according to investigator needs and institutional policies, (5) define a self-scaling architecture that encourages voluntary regional collaborations that coalesce to form a nationwide network. RESULTS: Our model has been validated by a large-scale, multi-institution study involving seven medical centers for cancer research. It is the basis of one of four open architectures developed under funding from the Office of the National Coordinator of Health Information Technology, fulfilling the biosurveillance use case defined by the American Health Information Community. The model supports broad applicability for regional and national clinical information exchanges. CONCLUSIONS: This model shows the feasibility of an architecture wherein the requirements of care providers, investigators, and public health authorities are served by a distributed model that grants autonomy, protects privacy, and promotes participation.

Drug-drug interactions (DDIs) can lead to serious and potentially lethal adverse events. In recent years, several drugs have been withdrawn from the market due to interaction-related adverse events (AEs). Current methods for detecting DDIs rely on the accumulation of sufficient clinical evidence in the post-market stage - a lengthy process that often takes years, during which time numerous patients may suffer from the adverse effects of the DDI. Detection methods are further hindered by the extremely large combinatoric space of possible drug-drug-AE combinations. There is therefore a practical need for predictive tools that can identify potential DDIs years in advance, enabling drug safety professionals to better prioritize their limited investigative resources and take appropriate regulatory action. To meet this need, we describe Predictive Pharmacointeraction Networks (PPINs) - a novel approach that predicts unknown DDIs by exploiting the network structure of all known DDIs, together with other intrinsic and taxonomic properties of drugs and AEs. We constructed an 856-drug DDI network from a 2009 snapshot of a widely-used drug safety database, and used it to develop PPIN models for predicting future DDIs. We compared the DDIs predicted based solely on these 2009 data, with newly reported DDIs that appeared in a 2012 snapshot of the same database. Using a standard multivariate approach to combine predictors, the PPIN model achieved an AUROC (area under the receiver operating characteristic curve) of 0.81 with a sensitivity of 48% given a specificity of 90%. An analysis of DDIs by severity level revealed that the model was most effective for predicting "contraindicated" DDIs (AUROC = 0.92) and less effective for "minor" DDIs (AUROC = 0.63). These results indicate that network based methods can be useful for predicting unknown drug-drug interactions.