Digitizing clinical trials.

Clinical trials are a fundamental tool used to evaluate the efficacy and safety of new drugs and medical devices and other health system interventions. The traditional clinical trials system acts as a quality funnel for the development and implementation of new drugs, devices and health system interventions. The concept of a "digital clinical trial" involves leveraging digital technology to improve participant access, engagement, trial-related measurements, and/or interventions, enable concealed randomized intervention allocation, and has the potential to transform clinical trials and to lower their cost. In April 2019, the US National Institutes of Health (NIH) and the National Science Foundation (NSF) held a workshop bringing together experts in clinical trials, digital technology, and digital analytics to discuss strategies to implement the use of digital technologies in clinical trials while considering potential challenges. This position paper builds on this workshop to describe the current state of the art for digital clinical trials including (1) defining and outlining the composition and elements of digital trials; (2) describing recruitment and retention using digital technology; (3) outlining data collection elements including mobile health, wearable technologies, application programming interfaces (APIs), digital transmission of data, and consideration of regulatory oversight and guidance for data security, privacy, and remotely provided informed consent; (4) elucidating digital analytics and data science approaches leveraging artificial intelligence and machine learning algorithms; and (5) setting future priorities and strategies that should be addressed to successfully harness digital methods and the myriad benefits of such technologies for clinical research.

The phenotypical implications of immune dysregulation in fragile X syndrome.

BACKGROUND AND PURPOSE: Immune system dysfunction and inflammatory dysregulation have been shown in several animal models of fragile X syndrome (FXS). However, the phenotypical implications of this dysregulation have not been systematically evaluated in a large patient cohort. METHODS: Five thousand seven hundred thirty-six FXS patients from a nationwide health insurance database were identified and compared to 573 600 age- and sex-matched controls. The phenome-wide association studies codes of FXS patients and those without FXS were compared and the false discovery rate was controlled at 0.05 using the Benjamini-Hochberg procedure. RESULTS: In addition to the commonly reported comorbidities of FXS, an over-representation of infectious diseases, including otitis media, cellulitis and abscess of fingers or toes, viral enteritis, candidiasis and pneumonia, was discovered. In addition, there was an under-representation of autoimmune disorders in FXS patients. CONCLUSIONS: Our systematic comorbidity analyses identified immunologically-based phenotypes associated with FXS. Our findings align with previous observations of compromised immunity and phagocytic defects in animal models of FXS. These results suggest the importance of immune-related pathways in FXS patients and their relevance to the FMR1 gene.

Grappling with the Future Use of Big Data for Translational Medicine and Clinical Care.

Objectives: Although patients may have a wealth of imaging, genomic, monitoring, and personal device data, it has yet to be fully integrated into clinical care. Methods: We identify three reasons for the lack of integration. The first is that "Big Data" is poorly managed by most Electronic Medical Record Systems (EMRS). The data is mostly available on "cloud-native" platforms that are outside the scope of most EMRs, and even checking if such data is available on a patient often must be done outside the EMRS. The second reason is that extracting features from the Big Data that are relevant to healthcare often requires complex machine learning algorithms, such as determining if a genomic variant is protein-altering. The third reason is that applications that present Big Data need to be modified constantly to reflect the current state of knowledge, such as instructing when to order a new set of genomic tests. In some cases, applications need to be updated nightly. Results: A new architecture for EMRS is evolving which could unite Big Data, machine learning, and clinical care through a microservice-based architecture which can host applications focused on quite specific aspects of clinical care, such as managing cancer immunotherapy. Conclusion: Informatics innovation, medical research, and clinical care go hand in hand as we look to infuse science-based practice into healthcare. Innovative methods will lead to a new ecosystem of applications (Apps) interacting with healthcare providers to fulfill a promise that is still to be determined.

The role and impact of research agendas on the comparative-effectiveness research among antihyperlipidemics.

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.

Effect of environmental factors on the spatio-temporal patterns of influenza spread.

Although spatio-temporal patterns of influenza spread often suggest that environmental factors play a role, their effect on the geographical variation in the timing of annual epidemics has not been assessed. We examined the effect of solar radiation, dew point, temperature and geographical position on the city-specific timing of epidemics in the USA. Using paediatric in-patient data from hospitals in 35 cities for each influenza season in the study period 2000-2005, we determined 'epidemic timing' by identifying the week of peak influenza activity. For each city we calculated averages of daily climate measurements for 1 October to 31 December. Bayesian hierarchical models were used to assess the strength of association between each variable and epidemic timing. Of the climate variables only solar radiation was significantly related to epidemic timing (95% CI -0.027 to -0.0032). Future studies may elucidate biological mechanisms intrinsically linked to solar radiation that contribute to epidemic timing in temperate regions.

Implementation of laboratory order data in BioSense Early Event Detection and Situation Awareness System.

INTRODUCTION: Laboratory test orders constitute an early outbreak data source. CDC receives laboratory order data in HL7 format from the Laboratory Corporation of America (LabCorp) and plans to use the data in the BioSense Early Event Detection and Situation Awareness System. METHODS: These LabCorp data contain information on tests ordered and include the type of test ordered and the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)-coded reasons for the order. A consensus panel was formed to group test orders on the basis of expert opinion into eight standard syndrome categories to provide an additional data source for early outbreak detection. A laboratory order taxonomy was developed and used in the mapping consolidation phase. The five main classes of this taxonomy are miscellaneous functional tests, fluid screening tests, system-specific tests, tests for specific infections (by primary manifestation), and tests for specific noninfectious diseases. RESULTS: Summary of numbers of laboratory order codes in each syndrome category are fever (53), respiratory (53), gastrointestinal (27), neurological (35), rash (37), lymphadenitis (20), localized cutaneous lesion (11), and specific infection (63). CONCLUSION: With the daily use of laboratory order data in BioSense, the actual distribution of laboratory order codes in syndrome groups can be evaluated, allowing modification of the mapping.

Simulation for assessing statistical methods of biologic terrorism surveillance.

INTRODUCTION: Multiple systems have been developed that use surveillance of health-care encounters to provide early warning of a terrorist attack. Limited practical experience and the absence of adequate theoretical assessments have precluded determining which alarm-generating algorithms should be preferred. In the absence of practical and theoretical results, choosing a particular statistical algorithm can be difficult. One way to evaluate algorithms is through simulation. OBJECTIVES: This report describes conceptual features of an example simulation based on the dispersal of anthrax spores and presents results based on the example simulation. METHODS: A simulation was implemented based on the dispersal of anthrax spores from a crop-dusting plane. Simulated cases were then included into an observed data stream. Detection approaches included SaTScan trade mark and small area regression and testing (SMART) scores. An evaluation metric was developed for comparison of results. In addition, a simulation of a separate data stream was added; and then separate and combined surveillance data were compared. RESULTS: In the simulation in which a single data stream was used, the two statistical approaches were substantially similar in performance. The combined surveillance based on two data streams is superior to surveillance based on either stream separately. CONCLUSION: The other potential uses of such a system are considered. These uses include the comparison of different data sources (e.g., outpatient versus emergency department and evaluating the impact of potential changes to the surveillance system, and increasing the population under surveillance). Simulation is a valuable technique for evaluating and planning for syndromic surveillance.

Connecting health departments and providers: syndromic surveillance's last mile.

INTRODUCTION: A critical need exists for mechanisms to identify and report acute illness clusters to health departments. The Massachusetts Department of Public Health (MDPH) works with partner organizations to conduct syndromic surveillance. This effort is based on CDC's Health Alert Network program and includes automated generation and notification of signals and a mechanism to obtain detailed clinical information when needed. METHODS: Syndromic surveillance partners collect emergency department and ambulatory care data. The principal communications platform between syndromic surveillance partners and MDPH is the Massachusetts Homeland and Health Alert Network (HHAN). This Internet-based application serves as a portal for communication and collaboration and alerts predefined groups of users involved in emergency response. Syndromic surveillance partners' systems report to HHAN by using Public Health Information Network Messaging System events that meet thresholds selected by MDPH. Cluster summaries are automatically posted into a document library. HHAN notifies users by electronic mail, alphanumeric pager, facsimile, or voice communications; users decide how they want to be notified for each level of alert. Discussion threads permit real-time communication among all parties. RESULTS: This automated alert system became operational in July 2004. During July-December 2004, HHAN facilitated communication and streamlined investigation of 15 alerts. CONCLUSION: The system allows rapid, efficient alerting and bidirectional communication among public health and private-sector partners and might be applicable to other public health agencies.

The personal internetworked notary and guardian.

In this paper, we propose a secure, distributed and scaleable infrastructure for a lifelong personal medical record system. We leverage on existing and widely available technologies, like the Web and public-key cryptography, to define an architecture that allows patients to exercise full control over their medical data. This is done without compromising patients' privacy and the ability of other interested parties (e.g. physicians, health-care institutions, public-health researchers) to access the data when appropriately authorized. The system organizes the information as a tree of encrypted plain-text XML files, in order to ensure platform independence and durability, and uses a role-based authorization scheme to assign access privileges. In addition to the basic architecture, we describe tools to populate the patient's record with data from hospital databases and the first testbed applications we are deploying.

Sensitivity of a clinical examination to predict need for radiography in children with ankle injuries: a prospective study.

BACKGROUND: Radiographs are ordered routinely for children with ankle trauma. We assessed the predictive value of a clinical examination to identify a predefined group of low-risk injuries, management of which would not be affected by absence of a radiograph. We aimed to show that no more than 1% of children with low-risk examinations (signs restricted to the distal fibula) would have high-risk fractures (all fractures except avulsion, buckle, and non-displaced Salter-Harris I and II fractures of the distal fibula), and to compare the potential reduction in radiography in children with low-risk examinations with that obtained by application of the Ottawa ankle rules (OAR). METHODS: Standard clinical examinations and subsequent radiographs were prospectively and independently evaluated in two tertiary-care paediatric emergency departments in North America. Eligible participants were healthy children aged 3-16 years with acute ankle injuries. Sample size, negative and positive predictive values, sensitivity, and specificity were calculated. McNemar's test was used to compare differences in the potential reduction in radiographs between the low-risk examination and the OAR. FINDINGS: 607 children were enrolled; 581 (95.7%) received follow-up. None of the 381 children with low-risk examinations had a high-risk fracture (negative predictive value 100% [95% CI 99.2-100]; sensitivity 100% [93.3-100]). Radiographs could be omitted in 62.8% of children with low-risk examinations, compared with only 12.0% reduction obtained by application of the OAR (p<0.0001). INTERPRETATION: A low-risk clinical examination in children with ankle injuries identifies 100% of high-risk diagnoses and may result in greater reduction of radiographic referrals than the OAR.

Costs and effectiveness of ultrasonography and limited computed tomography for diagnosing appendicitis in children.

BACKGROUND: A protocol of ultrasonography (US) followed by computed tomography with rectal contrast (CTRC) has been shown to be 94% accurate in the diagnosis of acute appendicitis in children. OBJECTIVE: To evaluate the changes in patient management and costs of a protocol using US and CTRC in the evaluation of appendicitis in children. DESIGN, SETTING, AND SUBJECTS: Prospective cohort study of 139 children between 3 and 21 years of age who had equivocal clinical findings for acute appendicitis seen in the emergency department of a large, urban pediatric teaching hospital between July 1998 and December 1998. PROTOCOL: Children with equivocal clinical presentations for acute appendicitis were prospectively evaluated with US. Patients with positive findings for acute appendicitis went directly to the operating room. Patients with negative or equivocal findings on US underwent CTRC. Surgical management plans were recorded before imaging, after US, and after CTRC. MAIN OUTCOME MEASURES: Surgical management plans before and after the imaging protocol as well as total hospital direct and indirect costs incurred or saved by each change in management were determined. Costs were obtained through the hospital's cost database and by ratios of costs to charges. RESULTS: Of the 139 children, the protocol resulted in a beneficial change in management in 86 children (61.9%), no change in management in 50 children (36.0%) and an incorrect change in management in 3 children (2.1%). US alone resulted in a beneficial change in management decision in 12/31 children (38.7%), while US followed by CTRC resulted in a beneficial change in management in 74/108 children (68.5%). The protocol resulted in a total cost savings of $78 503.99 or $565/patient. CONCLUSION: A protocol of US followed by CTRC in children with negative or equivocal US examinations results in a high rate of beneficial change in management as well as in total cost savings in children with equivocal clinical presentations for suspected appendicitis.

Effect of a reduced postpartum length of stay program on primary care services use by mothers and infants.

OBJECTIVE: To determine the impact of reduced postpartum length of stay (LOS) on primary care services use. METHODS. DESIGN: Retrospective quasiexperimental study, comparing 3 periods before and 1 period after introducing an intervention and adjusting for time trends. SETTING: A managed care plan. INTERVENTION: A reduced obstetrical LOS program (ROLOS), offering enhanced education and services. PARTICIPANTS: mother-infant dyads, delivered during 4 time periods: February through May 1992, 1993, and 1994, before ROLOS, and 1995, while ROLOS was in effect. INDEPENDENT MEASURES: Pre-ROLOS or the post-ROLOS year. OUTCOME MEASURES: Telephone calls, visits, and urgent care events during the first 3 weeks postpartum summed as total utilization events. RESULTS: Before ROLOS, LOS decreased gradually (from 51.6 to 44.3 hours) and after, sharply to 36.5 hours. Although primary care use did not increase before ROLOS, utilization for dyads increased during ROLOS. Before ROLOS, there were between 2.37 and 2.72 utilization events per day; after, there were 4.60. Well-child visits increased slightly to.98 visits per dyad, but urgent visits did not. CONCLUSION: This program resulted in shortened stays and more primary care use. There was no increase in infant urgent primary care utilization. Early discharge programs that incorporate and reimburse for enhanced ambulatory services may be safe for infants; these findings should not be extrapolated to mandatory reduced LOS initiatives without enhancement of care.

Growth and determinants of access in patient e-mail and Internet use.

OBJECTIVES: To measure the rate of access to and use of the Internet and e-mail, to determine sociodemographic predictors of access, and to measure the change in Internet and e-mail access over a 1-year interval. DESIGN: Survey study. Comparison of data with those from a similar survey from 1998. SETTING: Emergency department of a large urban pediatric teaching hospital. PARTICIPANTS: Primary caretakers of pediatric patients or the patients themselves if aged 16 years or older. MAIN OUTCOME MEASURES: Use of and access to the Internet or e-mail. RESULTS: We surveyed 214 individuals: 72.8% use or have access to the Internet, e-mail, or both, an increase from 52.2% in the 1998 survey (P<.001), and 48.5% regularly use the Internet or e-mail, compared with 43.1% in 1998 (P = .32). Outside the home, access is primarily at work (52.2%), schools (8.9%), public libraries (11.5%), and friends' and relatives' houses (16.7%). Internet use and access are linearly correlated with income (r = 0.43; P<.001). White patients are more likely to have access (odds ratio, 2.6; 95% confidence interval, 1.3-5.4; P<.001) than black or Asian patients, whereas those of Hispanic ethnicity are less likely to have access (odds ratio, 0.20; 95% confidence interval, 0.09-0.43; P<.001). However, after adjustment for race and Hispanic ethnicity, only income was a significant predictor of family access to the Internet and e-mail. CONCLUSIONS: During the past year, many patients have gained access to the Internet and e-mail, although rates of regular use have remained steady. This access is often from outside the home. Furthermore, access is directly related to income and is unevenly distributed across racial and ethnic groups.

Parents as direct contributors to the medical record: validation of their electronic input.

STUDY OBJECTIVES: We assessed the validity and completeness of data in the past medical history (PMH) obtained electronically from parents and examined effects of the human-computer interface and sociodemographic variables on electronic parental report. METHODS: We compared parents' electronic report of PMH data with a criterion standard, structured face-to-face interview by a pediatrician blinded to the electronic data. The electronic medical record interface enabled parents to provide 5 elements of the PMH: birth status, allergies, current medications, immunization status, and previous hospitalizations. The setting was the emergency department waiting room in an academic, urban children's hospital; parents of infants up to 12 months old participated. Outcome measures were validity of the PMH data obtained using the electronic medical record interface and odds of having an invalid or incomplete response using the electronic medical record interface. RESULTS: One hundred parents were enrolled (69.4% of eligible subjects). Study subjects did not differ from nonenrollees on demographic variables and visit characteristics. The validity of the electronic medical record interface data was high across the PMH elements (94% to 99%). Two demographic features predicted invalid response: parental primary language other than English or Spanish (odds ratio [OR] 11.4, 95% confidence interval CI 1.7 to 76.3), and Asian ethnicity (OR 14. 6, 95% CI 1.2 to 182.4). Incomplete responses were predicted by limited previous experience with computers; computer-naive subjects had an eightfold increased odds of skipping a question (OR 7.9, 95% CI 1.8 to 34.6). CONCLUSION: Parents are accurate independent reporters of their infants' general PMH using the electronic medical record interface. Their participation in care may be enhanced by allowing them to contribute medical information directly to the electronic medical record.

Four strategies for the management of esophageal coins in children.

OBJECTIVE: To compare clinical outcomes and costs under 4 strategies for the management of esophageal coins in children. METHODS: We developed a decision analysis model of 4 possible strategies for managing esophageal coins: 1) endoscopic removal under general anesthesia; 2) esophageal bougienage, 3) an outpatient 12- to 24-hour observation period to allow spontaneous coin passage; and 4) an inpatient observation period. Probabilities of success and complication rates for endoscopy and esophageal bougienage were obtained from published data. The probability of spontaneous coin passage was derived from chart review data at our institution. Costs were calculated from charges using a cost-to-charge ratio of.72. Hypothetical patients included in the model were those with a single esophageal coin presenting within 24 hours of ingestion, with no respiratory compromise on presentation and with no previous history of esophageal disease. Strategy-specific outcomes were overall complication rate and total cost in dollars per patient. Sensitivity analyses were performed to account for variations in the data. RESULTS: The esophageal bougienage strategy resulted in no complications and a total cost per patient of $382, which represents a marginal advantage of $2915 per patient compared with the endoscopic removal strategy. On sensitivity analysis over the range of success and complication rates of bougienage, this strategy maintained a considerable decrease in both overall complications and total cost per patient compared with all other strategies. Both outpatient and inpatient observation strategies had overall complication rates of 4.2% compared with the complication rate of 5.8% for the endoscopy strategy. The total cost per patient under these strategies was $2439 for the outpatient and $3141 for the inpatient strategy, representing a marginal advantage of $858 and $156 per patient, respectively, compared with the endoscopy strategy. Both observation strategies maintained a lower overall complication rate compared with endoscopy in the sensitivity analysis. The outpatient observation strategy maintained a marginal advantage of $645 to $1257 per patient compared with endoscopy; however, the inpatient observation strategy total cost per patient surpassed that of endoscopy at a spontaneous passage rate <23%. CONCLUSIONS: Given the high success and low complication rates reported for esophageal bougienage, substantial savings in overall complications and costs would be expected with the use of this procedure. With spontaneous passage rates >23%, either an outpatient or an inpatient observation strategy would reduce costs and complications, compared with endoscopic removal of all esophageal coins.

Time to detection of positive cultures in 28- to 90-day-old febrile infants.

OBJECTIVE: To determine the time to detection of positive blood, urine, and cerebrospinal fluid (CSF) cultures among febrile 28- to 90-day-old infants. STUDY DESIGN: Retrospective cohort of consecutive 28- to 90-day-old infants presenting with a temperature of >/=38 degrees C to an urban pediatric emergency department. Positive cultures and times to detection were noted. Patients were categorized as being at high risk for serious bacterial illness (SBI) based on clinical and laboratory criteria. RESULTS: Of the 3166 febrile infants seen in the emergency department during the study, 2733 had blood (86%), 2517 had urine (80%), and 2361 had CSF (75%) specimens obtained for culture, and 2190 had all 3 cultures (69%) sent. There were 224 positive cultures in 214 patients; of these, 191 had all 3 cultures (89%) sent. Subsequent analyses were confined to those who had all 3 cultures sent. The detected rate of SBI was 8.7% (191/2190). There were 28 positive blood cultures (1. 3%), 165 positive urine cultures (7.5%), and 8 positive CSF cultures (.4%). Median time to detection of positive cultures was 16 hours for blood, 16 hours for urine, and 18 hours for CSF. Four blood cultures (.1%), 20 urine cultures (.9%), and 0 CSF cultures were noted to have growth of a pathogen >24 hours after the specimen was obtained. All 4 blood cultures and 17 of 20 urine cultures with growth noted after 24 hours occurred among high-risk patients. CONCLUSIONS: The risk of identifying SBI after 24 hours is 1.1% among all 28- to 90-day-old febrile infants and.3% in low-risk infants.

Data quality and the electronic medical record: a role for direct parental data entry.

INTRODUCTION: The paper and electronic medical record (EMR) have evolved with little scientific inquiry into what effect the informant (clinician or patient) has on the validity of the recorded information. We have previously reported on an electronic interview program that facilitated parents' direct reporting of past medical history data. We sought to define additional data elements that parents could report electronically and to compare parents' electronically entered data to that charted by physicians using the current EMR system. METHODS: A convenience sample of parents was recruited to enter data on history of present illness (HPI) and review of systems (ROS) elements using an electronic interview. Data from the electronic parental interview and information abstracted from the physician EMR were compared to data derived from a face-to-face criterion standard interview. Validity, sensitivity and specificity of each mode of data entry were calculated. RESULTS: 100 of 140 eligible parents (71.4%) participated. Validity of information from the electronic interview was comparable to that charted by emergency physicians for HPI regarding fever and ROS questions. Sensitivity of parents' electronic interview was superior to physicians' charting for ROS elements specific to hydration status. CONCLUSIONS: Improved sensitivity for detection of historical risk factors for illness can be achieved by augmenting the pediatric EMR with a section for direct parental direct data input. Direct parental data input to the EMR should be considered to improve the quality of documentation for medical histories.

Healthconnect: clinical grade patient-physician communication.

A critical mass of Internet users is leading to a wide diffusion of electronic communications within medical practice. Unless implemented with substantial forethought, these new technological linkages could disturb delicate balances in the doctor-patient relationship, threaten the privacy of medical information, widen social disparity in health outcomes, and even function as barriers to access. The American Medical Informatics Association (AMIA) recently published recommendations to guide computer-based communications between clinicians and patients. This paper describes the motivations for and the design of HealthConnect, a web-based patient-doctor communications tool currently in use at Children's Hospital, Boston. Structural and process-oriented features of HealthConnect, as they relate to promotion of adherence with the Guidelines, are discussed.

The spontaneous passage of esophageal coins in children.

OBJECTIVES: To determine the likelihood of spontaneous passage of esophageal coins to the stomach in children and to determine the effect of initial coin location on spontaneous passage. DESIGN: Retrospective review of medical records and radiographs. SUBJECTS: Consecutive patients 18 years or younger presenting during a 24-month period (October 1995 to September 1997) whose evaluation revealed an esophageal coin. SETTING: The emergency department of a large, urban academic children's hospital. MAIN OUTCOME MEASURES: Independent measures were time between ingestion and radiographs, initial location of the coin, and categorization of case as "simple" (patients without a history of esophageal disease or surgery, with a single esophageal coin lodged less than 24 hours, and with no respiratory compromise on presentation) or "complex." Dependent measures were spontaneous passage of the coin to the stomach and the time to passage. RESULTS: A total of 116 cases were included in the analysis, of which 84 were simple and 32 complex. Among the 84 simple cases, the coin was initially located in the proximal third of the esophagus in 54 (64%), the middle third in 7 (8%), and the distal third in 22 (26%). For the 32 complex cases, the initial location of the coin was the proximal third of the esophagus in 27 (84%) and the middle third in 5 (16%). Subsequent radiographs were obtained in the emergency department in 58 (69%) of the simple cases. Among these cases, spontaneous passage of the coin to the stomach occurred in 16 (28% [95% confidence interval, 21%-41%]). By initial coin location, spontaneous passage in this group occurred in 22% (7/32) of proximal, 33% (2/6) of middle, and 37% (7/19) of distal esophageal coins (P >.05). Subsequent radiographs were obtained in 14 (44%) of the complex cases; no coin had passed spontaneously to the stomach in these patients (0% [95% confidence interval, 0%-20%]). CONCLUSIONS: Children with a single esophageal coin seen within 24 hours of ingestion, who have no history of esophageal disease and no respiratory compromise on presentation, have a 28% chance of spontaneous passage of the coin to the stomach. Coins in the upper as well as the lower esophagus pass spontaneously. Observing these children for 12 to 24 hours prior to invasive procedures will reduce complications and costs.