Cross Disciplinary Consultancy to Bridge Public Health Technical Needs and Analytic Developers: Negation Detection Use Case.

This paper describes a continuing initiative of the International Society for Disease Surveillance designed to bring together public health practitioners and analytics solution developers from both academia and industry. Funded by the Defense Threat Reduction Agency, a series of consultancies have been conducted on a range of topics of pressing concern to public health (e.g. developing methods to enhance prediction of asthma exacerbation, developing tools for asyndromic surveillance from chief complaints). The topic of this final consultancy, conducted at the University of Utah in January 2017, is focused on defining a roadmap for the development of algorithms, tools, and datasets for improving the capabilities of text processing algorithms to identify negated terms (i.e. negation detection) in free-text chief complaints and triage reports.

Comparison of crowd-sourced, electronic health records based, and traditional health-care based influenza-tracking systems at multiple spatial resolutions in the United States of America.

BACKGROUND: Influenza causes an estimated 3000 to 50,000 deaths per year in the United States of America (US). Timely and representative data can help local, state, and national public health officials monitor and respond to outbreaks of seasonal influenza. Data from cloud-based electronic health records (EHR) and crowd-sourced influenza surveillance systems have the potential to provide complementary, near real-time estimates of influenza activity. The objectives of this paper are to compare two novel influenza-tracking systems with three traditional healthcare-based influenza surveillance systems at four spatial resolutions: national, regional, state, and city, and to determine the minimum number of participants in these systems required to produce influenza activity estimates that resemble the historical trends recorded by traditional surveillance systems. METHODS: We compared influenza activity estimates from five influenza surveillance systems: 1) patient visits for influenza-like illness (ILI) from the US Outpatient ILI Surveillance Network (ILINet), 2) virologic data from World Health Organization (WHO) Collaborating and National Respiratory and Enteric Virus Surveillance System (NREVSS) Laboratories, 3) Emergency Department (ED) syndromic surveillance from Boston, Massachusetts, 4) patient visits for ILI from EHR, and 5) reports of ILI from the crowd-sourced system, Flu Near You (FNY), by calculating correlations between these systems across four influenza seasons, 2012-16, at four different spatial resolutions in the US. For the crowd-sourced system, we also used a bootstrapping statistical approach to estimate the minimum number of reports necessary to produce a meaningful signal at a given spatial resolution. RESULTS: In general, as the spatial resolution increased, correlation values between all influenza surveillance systems decreased. Influenza-like Illness rates in geographic areas with more than 250 crowd-sourced participants or with more than 20,000 visit counts for EHR tracked government-lead estimates of influenza activity. CONCLUSIONS: With a sufficient number of reports, data from novel influenza surveillance systems can complement traditional healthcare-based systems at multiple spatial resolutions.

Accurate Influenza Monitoring and Forecasting Using Novel Internet Data Streams: A Case Study in the Boston Metropolis.

BACKGROUND: Influenza outbreaks pose major challenges to public health around the world, leading to thousands of deaths a year in the United States alone. Accurate systems that track influenza activity at the city level are necessary to provide actionable information that can be used for clinical, hospital, and community outbreak preparation. OBJECTIVE: Although Internet-based real-time data sources such as Google searches and tweets have been successfully used to produce influenza activity estimates ahead of traditional health care-based systems at national and state levels, influenza tracking and forecasting at finer spatial resolutions, such as the city level, remain an open question. Our study aimed to present a precise, near real-time methodology capable of producing influenza estimates ahead of those collected and published by the Boston Public Health Commission (BPHC) for the Boston metropolitan area. This approach has great potential to be extended to other cities with access to similar data sources. METHODS: We first tested the ability of Google searches, Twitter posts, electronic health records, and a crowd-sourced influenza reporting system to detect influenza activity in the Boston metropolis separately. We then adapted a multivariate dynamic regression method named ARGO (autoregression with general online information), designed for tracking influenza at the national level, and showed that it effectively uses the above data sources to monitor and forecast influenza at the city level 1 week ahead of the current date. Finally, we presented an ensemble-based approach capable of combining information from models based on multiple data sources to more robustly nowcast as well as forecast influenza activity in the Boston metropolitan area. The performances of our models were evaluated in an out-of-sample fashion over 4 influenza seasons within 2012-2016, as well as a holdout validation period from 2016 to 2017. RESULTS: Our ensemble-based methods incorporating information from diverse models based on multiple data sources, including ARGO, produced the most robust and accurate results. The observed Pearson correlations between our out-of-sample flu activity estimates and those historically reported by the BPHC were 0.98 in nowcasting influenza and 0.94 in forecasting influenza 1 week ahead of the current date. CONCLUSIONS: We show that information from Internet-based data sources, when combined using an informed, robust methodology, can be effectively used as early indicators of influenza activity at fine geographic resolutions.

Surgery and magnetic resonance imaging increase the risk of hypothermia in infants.

AIM: Maintaining normothermia is a tenet of neonatal care. However, neonatal thermal care guidelines applicable to intra-hospital transport beyond the neonatal intensive care unit (NICU) and during surgery or magnetic resonance imaging (MRI) are lacking. The aim of this study is to determine the proportion of infants normothermic (36.5-37.5°C) on return to NICU after management during surgery and MRI, and during standard clinical care in both environments. METHODS: Sixty-two newborns requiring either surgery in the operating theatre (OT) (n = 41) or an MRI scan (n = 21) at the Royal Children's Hospital (Melbourne) NICU were prospectively studied. Core temperature, along with cardiorespiratory parameters, was continuously measured from 15 min prior to leaving the NICU until 60 min after returning. Passive and active warming (intra-operatively) was at clinician discretion. RESULTS: The study reported 90% of infants were normothermic before leaving NICU: 86% (MRI) and 93% (OT). Only 52% of infants were normothermic on return to NICU (relative risk (RR) 1.75; 95% confidence interval (CI) 1.39-2.31; number needed to harm (NNH) 2.6). Between departure from the NICU and commencement of surgery, core temperature decreased by mean 0.81°C (95% CI 0.30-1.33; P = 0.0001, analysis of variance), with only 24% of infants normothermic when surgery began (P < 0.0001; RR 3.80 (95% CI 2.33-6.74); NNH 1.5). After an MRI, infants were a mean 0.41°C (95% CI 0.16-0.67) colder than immediately before entering the scanner (P = 0.001, analysis of variance), with only 43% being normothermic (P = 0.003; RR 2.11 (95% CI 1.35-3.74); NNH 2.1). CONCLUSION: Unintentional hypothermia is a common occurrence during surgery in the OT and MRI in neonates, indicating that evidence-based warming strategies to prevent hypothermia should be developed.

Cognition and behaviour in children with congenital abdominal wall defects.

AIM: To characterise neurodevelopment at age two years and cognition and behaviour at age five years in children born with abdominal wall defects (gastroschisis or exomphalos). STUDY DESIGN: Participants were treated as neonates for gastroschisis or exomphalos and invited for routine clinical follow-up at ages two and five years. Thirty-nine two year-olds and 20 five year-olds with gastroschisis and 20 two year-olds and 10 five year-olds with exomphalos returned for age-appropriate assessments of development (two years) and intellectual functioning (IQ), executive function, and behavioural problems. Results were compared with normative data from the tests and published data from local term-born children. RESULTS: For both gastroschisis and exomphalos two year-olds, neurodevelopment was in line with the test normative data, but below the level of local normative data for all domains (effect sizes from -0.4 to -1.4 standard deviations). At five years, children with gastroschisis performed similarly to the normative mean for IQ but had high rates of various executive functioning problems on parent report (18-41% compared with 7% expected from norms). There was also a tendency for increased frequency of internalising problems (33% compared with normative expectation of 16%). Five year-olds with exomphalos also performed similarly to the normative mean for IQ and had low rates of executive and behavioural problems. CONCLUSIONS: Survivors of gastroschisis and exomphalos may be at risk of poor neurodevelopment in toddlerhood, depending on the reference group, and children with gastroschisis may be particularly at risk for executive functioning difficulties despite an IQ within normal limits.

Perioperative risk factors for impaired neurodevelopment after cardiac surgery in early infancy.

OBJECTIVE: Historical cohort studies have reported adverse neurodevelopment following cardiac surgery during early infancy. Advances in surgical techniques and perioperative care have coincided with updating of neurodevelopmental assessment tools. We aimed to determine perioperative risk factors for impaired neurodevelopment at 2 years following surgery for congenital heart disease (CHD) in early infancy. DESIGN AND PATIENTS: We undertook a prospective longitudinal study of 153 full-term infants undergoing surgery for CHD before 2 months of age. Infants were excluded if they had a genetic syndrome associated with neurodevelopmental impairment. OUTCOME MEASURES: Predefined perioperative parameters were recorded and infants were classified according to cardiac anatomy. At 2 years, survivors were assessed using the Bayley Scales of Infant Development-III. RESULTS: At 2 years, 130 children (98% of survivors) were assessed. Mean cognitive, language and motor scores were 93.4±13.6, 93.6±16.1 and 96.8±12.5 respectively (100±15 norm). Twenty (13%) died and 12 (9%) survivors had severe impairment (score <70), mostly language (8%). The lowest scores were in infants born with single ventricle physiology with obstruction to the pulmonary circulation who required a neonatal systemic-to-pulmonary artery shunt. Additional risk factors for impairment included reduced gestational age, postoperative elevation of lactate or S100B and repeat cardiac surgery. CONCLUSIONS: In the modern era of infant cardiac surgery and perioperative care, children continue to demonstrate neurodevelopmental delays. The use of updated assessment tools has revealed early language dysfunction and relative sparing of motor function. Ongoing follow-up is critical in this high-risk population.

Relationship between Social-Emotional and Neurodevelopment of 2-Year-Old Children with Congenital Heart Disease.

OBJECTIVE: The purpose of this study was to describe social-emotional outcomes and the relationship with neurodevelopmental outcomes in a cohort of 2-year-old children who underwent surgery for congenital heart disease (CHD) in infancy, and explore the relationship between the outcomes and parental and surgical factors. DESIGN: A two-center prospective cross-sectional cohort study. PATIENTS: A cohort of 105 2-year-olds who underwent surgery in infancy for severe CHD MEASURES: Social-emotional and neurodevelopment was evaluated with the Infant and Toddler Social and Emotional Assessment tool (ITSEA), and the Bayley Scales of Infant Toddler Development, Third Edition. RESULTS: Neurodevelopment was delayed in the CHD cohort with significantly worse results compared to published Australian-based norms in all domains (P < .001) and in the Cognitive (P < .001) and Language (P < .001) domains with respect to the reported American norms. Social-emotional outcome was similar to Australian norms in all domains but better than the American based norms in the Internalizing domain (P < .05). Higher maternal education was associated to better neurodevelopmental outcome in all domains and better scores in the internalizing and externalizing domains of the ITSEA. There was a moderate correlation (r = 0.43, P < .001) between Language and social-emotional competence. Motor development was influenced by the need for a significant cardiac reoperation. CONCLUSIONS: The influences of social factors may be underestimated in the outcome of children with CHD. Language development in those with CHD may be improved with intervention targeting social-emotional competence; further research is needed in this area.

Cross-Disciplinary Consultancy to Enhance Predictions of Asthma Exacerbation Risk in Boston.

This paper continues an initiative conducted by the International Society for Disease Surveillance with funding from the Defense Threat Reduction Agency to connect near-term analytical needs of public health practice with technical expertise from the global research community. The goal is to enhance investigation capabilities of day-to-day population health monitors. A prior paper described the formation of consultancies for requirements analysis and dialogue regarding costs and benefits of sustainable analytic tools. Each funded consultancy targets a use case of near-term concern to practitioners. The consultancy featured here focused on improving predictions of asthma exacerbation risk in demographic and geographic subdivisions of the city of Boston, Massachusetts, USA based on the combination of known risk factors for which evidence is routinely available. A cross-disciplinary group of 28 stakeholders attended the consultancy on March 30-31, 2016 at the Boston Public Health Commission. Known asthma exacerbation risk factors are upper respiratory virus transmission, particularly in school-age children, harsh or extreme weather conditions, and poor air quality. Meteorological subject matter experts described availability and usage of data sources representing these risk factors. Modelers presented multiple analytic approaches including mechanistic models, machine learning approaches, simulation techniques, and hybrids. Health department staff and local partners discussed surveillance operations, constraints, and operational system requirements. Attendees valued the direct exchange of information among public health practitioners, system designers, and modelers. Discussion finalized design of an 8-year de-identified dataset of Boston ED patient records for modeling partners who sign a standard data use agreement.

Laboratory-acquired vaccinia virus infection in a recently immunized person--Massachusetts, 2013.

On November 26, 2013, the CDC poxvirus laboratory was notified by the Boston Public Health Commission (BPHC) of an inadvertent inoculation of a recently vaccinated (ACAM2000 smallpox vaccine) laboratory worker with wild type vaccinia virus (VACV) Western Reserve. A joint investigation by CDC and BPHC confirmed orthopoxvirus infection in the worker, who had reported a needle stick in his thumb while inoculating a mouse with VACV. He experienced a non-tender, red rash on his arm, diagnosed at a local emergency department as cellulitis. He subsequently developed a necrotic lesion on his thumb, diagnosed as VACV infection. Three weeks after the injury, the thumb lesion was surgically debrided and at 2 months post-injury, the skin lesion had resolved. The investigation confirmed that the infection was the first reported VACV infection in the United States in a laboratory worker vaccinated according to the Advisory Committee on Immunization Practices (ACIP) recommendations. The incident prompted the academic institution to outline biosafety measures for working with biologic agents, such as biosafety training of laboratory personnel, vaccination (if appropriate), and steps in incident reporting. Though vaccination has been shown to be an effective measure in protecting personnel in the laboratory setting, this case report underscores the importance of proper safety measures and incident reporting.

Cross-Disciplinary Consultancy to Bridge Public Health Technical Needs and Analytic Developers: Asyndromic Surveillance Use Case.

INTRODUCTION: We document a funded effort to bridge the gap between constrained scientific challenges of public health surveillance and methodologies from academia and industry. Component tasks are the collection of epidemiologists' use case problems, multidisciplinary consultancies to refine them, and dissemination of problem requirements and shareable datasets. We describe an initial use case and consultancy as a concrete example and challenge to developers. MATERIALS AND METHODS: Supported by the Defense Threat Reduction Agency Biosurveillance Ecosystem project, the International Society for Disease Surveillance formed an advisory group to select tractable use case problems and convene inter-disciplinary consultancies to translate analytic needs into well-defined problems and to promote development of applicable solution methods. The initial consultancy's focus was a problem originated by the North Carolina Department of Health and its NC DETECT surveillance system: Derive a method for detection of patient record clusters worthy of follow-up based on free-text chief complaints and without syndromic classification. RESULTS: Direct communication between public health problem owners and analytic developers was informative to both groups and constructive for the solution development process. The consultancy achieved refinement of the asyndromic detection challenge and of solution requirements. Participants summarized and evaluated solution approaches and discussed dissemination and collaboration strategies. PRACTICE IMPLICATIONS: A solution meeting the specification of the use case described above could improve human monitoring efficiency with expedited warning of events requiring follow-up, including otherwise overlooked events with no syndromic indicators. This approach can remove obstacles to collaboration with efficient, minimal data-sharing and without costly overhead.

Subdural hemorrhage and hypoxia in infants with congenital heart disease.

BACKGROUND AND OBJECTIVES: It has been suggested that there is a causal relationship between hypoxia and subdural hemorrhage (SDH) in infancy. The purpose of this study was to review the incidence of SDH in infants with congenital heart disease and explore the relationship between SDH and hypoxia. METHODS: Review of data collected for a prospective longitudinal cohort study of infants undergoing surgery for congenital heart disease in New Zealand and Australia. Infants underwent serial MRI scans of the brain in the first 3 months of life. All oxygen saturation recordings and MRI results were extracted and infants assigned to categories by degree of hypoxia. The data were then examined for any statistically significant relationship between hypoxia and SDH. RESULTS: One hundred fifty-two infants underwent MRI scans, and 66 (43%) had 145 loci of SDH. New SDH was seen in 12 infants after cardiac surgery. Of the loci of SDH, 63 (43%) were supratentorial, and most of these were interhemispheric, parietal, or temporal. SDH present on the first MRI persisted beyond 28 days of life in 8 infants. There was no demonstrable relationship between SDH and hypoxia. CONCLUSIONS: Asymptomatic SDH is common in young infants with congenital heart disease, at a frequency similar to that of those without congenital heart disease. These SDHs may occur in locations where they occur in abusive head trauma, but they are typically small and resolve within 3 months of birth. We were unable to demonstrate any association between hypoxia and SDH in this cohort.

Usefulness of routine head ultrasound scans before surgery for congenital heart disease.

OBJECTIVE: The purpose of this study was to assess the utility of preoperative head ultrasound scan (HUS) in a cohort of newborns also undergoing preoperative MRI as part of a prospective research study of brain injury in infants having surgery for congenital heart disease (CHD). METHODS: A total of 167 infants diagnosed with CHD were included in this 3-center study. None of the patients had clinical signs or symptoms of preoperative brain injury, and all patients received both HUS and brain MRI before undergoing surgical intervention. HUS and MRI results were reported by experienced neuroradiologists who were blinded to any specific clinical details of the study participants. The findings of the individual imaging modes were compared to evaluate for the presence of brain injury. RESULTS: Preoperative brain injury was present on HUS in 5 infants (3%) and on MRI in 44 infants (26%) (P < .001). Four of the HUS showed intraventricular hemorrhage not seen on MRI, suggesting false-positive results, and the fifth showed periventricular leukomalacia. The predominant MRI abnormality was white matter injury (n = 32). Other findings included infarct (n = 16) and hemorrhage (n = 5). CONCLUSIONS: Preoperative brain injury on MRI was present in 26% of infants with CHD, but only 3% had any evidence of brain injury on HUS. Among positive HUS, 80% were false-positive results. Our findings suggest that routine HUS is not indicated in asymptomatic term or near-term neonates undergoing surgery for CHD, and MRI may be a preferable tool when the assessment of these infants is warranted.

New white matter brain injury after infant heart surgery is associated with diagnostic group and the use of circulatory arrest.

BACKGROUND: Abnormalities on magnetic resonance imaging scans are common both before and after surgery for congenital heart disease in early infancy. The aim of this study was to prospectively investigate the nature, timing, and consequences of brain injury on magnetic resonance imaging in a cohort of young infants undergoing surgery for congenital heart disease both with and without cardiopulmonary bypass. METHODS AND RESULTS: A total of 153 infants undergoing surgery for congenital heart disease at <8 weeks of age underwent serial magnetic resonance imaging scans before and after surgery and at 3 months of age, as well as neurodevelopmental assessment at 2 years of age. White matter injury (WMI) was the commonest type of injury both before and after surgery. It occurred in 20% of infants before surgery and was associated with a less mature brain. New WMI after surgery was present in 44% of infants and at similar rates after surgery with or without cardiopulmonary bypass. The most important association was diagnostic group (P<0.001). In infants having arch reconstruction, the use and duration of circulatory arrest were significantly associated with new WMI. New WMI was also associated with the duration of cardiopulmonary bypass, postoperative lactate level, brain maturity, and WMI before surgery. Brain immaturity but not brain injury was associated with impaired neurodevelopment at 2 years of age. CONCLUSIONS: New WMI is common after surgery for congenital heart disease and occurs at the same rate in infants undergoing surgery with and without cardiopulmonary bypass. New WMI is associated with diagnostic group and, in infants undergoing arch surgery, the use of circulatory arrest.

Perioperative amplitude-integrated EEG and neurodevelopment in infants with congenital heart disease.

PURPOSE: Perioperative brain injury is common in young infants undergoing cardiac surgery. We aimed to determine the relationship between perioperative electrical seizures, the background pattern of amplitude-integrated electroencephalography (aEEG) and 2-year neurodevelopmental outcome in young infants undergoing surgery for congenital heart disease. METHODS: A total of 150 newborn infants undergoing cardiac surgery underwent aEEG monitoring prior to and during surgery, and for 72 h postoperatively. Two blinded assessors reviewed the aEEGs for seizure activity and background pattern. Survivors underwent neurodevelopmental outcome assessment using the Bayley Scales of Infant Development (3rd edn.) at 2 years. RESULTS: The median age at surgery was 7 days (IQR 4-11). Cardiopulmonary bypass was used in 83 %. Perioperative electrical seizures occurred in 30 %, of whom 1/4 had a clinical correlate, but were not associated with 2-year outcome. Recovery to a continuous background occurred at a median 6 (3-13) h and sleep-wake cycling recovered at 21 (14-30) h. Prolonged aEEG recovery was associated with increased mortality and worse neurodevelopmental outcome. Failure of the aEEG to recover to a continuous background by 48 postoperative hours was associated with impairment in all outcome domains (p < 0.05). Continued abnormal aEEG at 7 postoperative days was highly associated with mortality (p < 0.001). CONCLUSIONS: Perioperative seizures were common in this cohort of infants but did not impact on 2-year neurodevelopmental outcome. Delayed recovery in aEEG background was associated with increased risk of early mortality and worse neurodevelopment. Ongoing monitoring of the survivors is essential to determine the longer-term significance of these findings.

Self-reported fever and measured temperature in emergency department records used for syndromic surveillance.

Many public health agencies monitor population health using syndromic surveillance, generally employing information from emergency department (ED) visit records. When combined with other information, objective evidence of fever may enhance the accuracy with which surveillance systems detect syndromes of interest, such as influenza-like illness. This study found that patient chief complaint of self-reported fever was more readily available in ED records than measured temperature and that the majority of patients with an elevated temperature recorded also self-reported fever. Due to its currently limited availability, we conclude that measured temperature is likely to add little value to self-reported fever in syndromic surveillance for febrile illness using ED records.

Amplitude-integrated electroencephalography and brain injury in infants undergoing Norwood-type operations.

BACKGROUND: Perioperative brain injury is common in infants undergoing cardiac surgery. Amplitude-integrated electroencephalography (aEEG) provides real-time neurologic monitoring and can identify seizures and abnormalities of background cerebral activity. We aimed to determine the incidence of perioperative electrical seizures, and to establish the background pattern of aEEG, in neonates undergoing Norwood-type palliations for complex congenital heart disease in relation to outcome at 2 years. METHODS: Thirty-nine full-term neonates undergoing Norwood-type operations underwent aEEG monitoring before and during surgery and for 72 hours postoperatively. The perfusion strategy included full-flow moderately hypothermic cardiopulmonary bypass with antegrade cerebral perfusion. Amplitude-integrated electroencephalography tracings were reviewed for seizure activity and background pattern. Survivors underwent neurodevelopmental outcome assessment using the Bayley Scales of Infant Development (3rd edition) at 2 years of age. RESULTS: Thirteen (33%) infants had electrical seizures, including 9 with intraoperative seizures and 7 with postoperative seizures. Seizures were associated with significantly increased mortality, but not with neurodevelopmental impairment in survivors. Delay in recovery of the aEEG background beyond 48 hours was also associated with increased mortality and worse motor development. CONCLUSIONS: Perioperative seizures were common in this cohort. Intraoperative seizures predominantly affected the left hemisphere during antegrade cerebral perfusion. Delayed recovery in aEEG background was associated with increased risk of early mortality and worse motor development. Ongoing monitoring is essential to determine the longer-term significance of these findings.

Developing syndrome definitions based on consensus and current use.

OBJECTIVE: Standardized surveillance syndromes do not exist but would facilitate sharing data among surveillance systems and comparing the accuracy of existing systems. The objective of this study was to create reference syndrome definitions from a consensus of investigators who currently have or are building syndromic surveillance systems. DESIGN: Clinical condition-syndrome pairs were catalogued for 10 surveillance systems across the United States and the representatives of these systems were brought together for a workshop to discuss consensus syndrome definitions. RESULTS: Consensus syndrome definitions were generated for the four syndromes monitored by the majority of the 10 participating surveillance systems: Respiratory, gastrointestinal, constitutional, and influenza-like illness (ILI). An important element in coming to consensus quickly was the development of a sensitive and specific definition for respiratory and gastrointestinal syndromes. After the workshop, the definitions were refined and supplemented with keywords and regular expressions, the keywords were mapped to standard vocabularies, and a web ontology language (OWL) ontology was created. LIMITATIONS: The consensus definitions have not yet been validated through implementation. CONCLUSION: The consensus definitions provide an explicit description of the current state-of-the-art syndromes used in automated surveillance, which can subsequently be systematically evaluated against real data to improve the definitions. The method for creating consensus definitions could be applied to other domains that have diverse existing definitions.