Opportunities, barriers, and recommendations in down syndrome research.

BACKGROUND: Recent advances in medical care have increased life expectancy and improved the quality of life for people with Down syndrome (DS). These advances are the result of both pre-clinical and clinical research but much about DS is still poorly understood. In 2020, the NIH announced their plan to update their DS research plan and requested input from the scientific and advocacy community. OBJECTIVE: The National Down Syndrome Society (NDSS) and the LuMind IDSC Foundation worked together with scientific and medical experts to develop recommendations for the NIH research plan. METHODS: NDSS and LuMind IDSC assembled over 50 experts across multiple disciplines and organized them in eleven working groups focused on specific issues for people with DS. RESULTS: This review article summarizes the research gaps and recommendations that have the potential to improve the health and quality of life for people with DS within the next decade. CONCLUSIONS: This review highlights many of the scientific gaps that exist in DS research. Based on these gaps, a multidisciplinary group of DS experts has made recommendations to advance DS research. This paper may also aid policymakers and the DS community to build a comprehensive national DS research strategy.

SPIRIT-PRO Extension explanation and elaboration: guidelines for inclusion of patient-reported outcomes in protocols of clinical trials.

Patient-reported outcomes (PROs) are used in clinical trials to provide valuable evidence on the impact of disease and treatment on patients' symptoms, function and quality of life. High-quality PRO data from trials can inform shared decision-making, regulatory and economic analyses and health policy. Recent evidence suggests the PRO content of past trial protocols was often incomplete or unclear, leading to research waste. To address this issue, international, consensus-based, PRO-specific guidelines were developed: the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT)-PRO Extension. The SPIRIT-PRO Extension is a 16-item checklist which aims to improve the content and quality of aspects of clinical trial protocols relating to PRO data collection to minimise research waste, and ultimately better inform patient-centred care. This SPIRIT-PRO explanation and elaboration (E&E) paper provides information to promote understanding and facilitate uptake of the recommended checklist items, including a comprehensive protocol template. For each SPIRIT-PRO item, we provide a detailed description, one or more examples from existing trial protocols and supporting empirical evidence of the item's importance. We recommend this paper and protocol template be used alongside the SPIRIT 2013 and SPIRIT-PRO Extension paper to optimise the transparent development and review of trial protocols with PROs.

Pregnancy latency after preterm premature rupture of membranes: oral versus intravenous antibiotics.

BACKGROUND: Following the destruction of pharmaceutical production facilities in Puerto Rico by Hurricane Maria in September 2017, a shortage of small-volume bags of sterile intravenous fluid for infusion led to a decreased ability to administer intravenous azithromycin and ampicillin efficiently for use in the treatment of patients with preterm premature rupture of membranes. OBJECTIVE: This study aimed to assess pregnancy latency after preterm premature rupture of membranes following treatment with oral-only antibiotics compared with treatment with intravenous antibiotics followed by oral antibiotics. STUDY DESIGN: This is a retrospective historic control study comparing women with preterm premature rupture of membranes who were initiated on a 7-day oral-only regimen of azithromycin and amoxicillin (modified regimen) during a 12-month period beginning December 2017 (during which time there was a shortage of small-volume bags of intravenous fluid) to women with preterm premature rupture of membranes who were initiated on a 2-day regimen of intravenous ampicillin and azithromycin followed by 5 days of oral amoxicillin and azithromycin (standard regimen) from December 2016 to December 2018. Women were included in the study if they were diagnosed with preterm premature rupture of membranes at <34 weeks' gestation and were started on latency antibiotics, and women were excluded from the study if they had a contraindication to expectant management, a cerclage, or suspected fetal anomalies. The primary outcome was pregnancy latency, defined as time from the first dose of antibiotics to delivery. RESULTS: The 37 women who received the modified regimen and the 79 women who received the standard regimen had similar baseline characteristics. Mean (standard deviation) gestational age at time of preterm premature rupture of membranes was similar between the modified (30.5 weeks' gestation [±3.1]) and standard regimen groups (30.2 weeks' gestation [±3.2]), and the rate of group B streptococcus rectovaginal colonization was similar for both groups (27% vs 24%; P=.95). Pregnancy latency did not differ in the modified vs standard regimen (mean difference, -0.15 days; 95% confidence interval, -4.87 to 4.58) There was no statistically significant difference in the relative risk of composite maternal infection (relative risk, 0.43; 95% confidence interval, 0.05-3.53) or composite neonatal infection (relative risk, 0.43; 95% confidence interval, 0.05-3.52). CONCLUSION: Although limited by small sample size, our study suggested that adoption of an oral-only antibiotic regimen for pregnancy latency following preterm premature rupture of membranes is worthy of further study.

An outbreak of oriental theileriosis in dairy cattle imported to Vietnam from Australia.

This study reports an outbreak of oriental theileriosis in dairy cattle imported to Vietnam from Australia. Following clinical and pathological diagnoses, a total of 112 cattle blood samples were divided into three groups and tested using multiplexed tandem PCR. Group 1 were from aborted heifers in Vietnam; group 2 were from cattle before shipment from group 1 cattle and group 3 were from the same batch of cattle but transported to Taiwan. Theileria orientalis DNA was detected in 72·3% cattle. The prevalences of T. orientalis in groups 1, 2 and 3 were 77·6, 86·9 and 57·5%, respectively, and the difference in prevalence was significant between groups 1 and 3 (P < 0·0001). The infection intensities of genotypes chitose and ikeda of T. orientalis were higher in groups 1 (57 721 and 33 709, respectively) and 3 (5897 and 61 766, respectively) than those in group 2 (2071 and 6331, respectively). Phylogenetic analyses of the major piroplasm surface protein sequences revealed that genotypes chitose and ikeda determined herein were closely related to those previously reported from Australia. This first report of an outbreak of oriental theileriosis in imported cattle emphasizes improved measures for the export and import of cattle infected with T. orientalis.

Automated movement correction for dynamic PET/CT images: evaluation with phantom and patient data.

Head movement during a dynamic brain PET/CT imaging results in mismatch between CT and dynamic PET images. It can cause artifacts in CT-based attenuation corrected PET images, thus affecting both the qualitative and quantitative aspects of the dynamic PET images and the derived parametric images. In this study, we developed an automated retrospective image-based movement correction (MC) procedure. The MC method first registered the CT image to each dynamic PET frames, then re-reconstructed the PET frames with CT-based attenuation correction, and finally re-aligned all the PET frames to the same position. We evaluated the MC method's performance on the Hoffman phantom and dynamic FDDNP and FDG PET/CT images of patients with neurodegenerative disease or with poor compliance. Dynamic FDDNP PET/CT images (65 min) were obtained from 12 patients and dynamic FDG PET/CT images (60 min) were obtained from 6 patients. Logan analysis with cerebellum as the reference region was used to generate regional distribution volume ratio (DVR) for FDDNP scan before and after MC. For FDG studies, the image derived input function was used to generate parametric image of FDG uptake constant (Ki) before and after MC. Phantom study showed high accuracy of registration between PET and CT and improved PET images after MC. In patient study, head movement was observed in all subjects, especially in late PET frames with an average displacement of 6.92 mm. The z-direction translation (average maximum = 5.32 mm) and x-axis rotation (average maximum = 5.19 degrees) occurred most frequently. Image artifacts were significantly diminished after MC. There were significant differences (P<0.05) in the FDDNP DVR and FDG Ki values in the parietal and temporal regions after MC. In conclusion, MC applied to dynamic brain FDDNP and FDG PET/CT scans could improve the qualitative and quantitative aspects of images of both tracers.

Hb Manukau [ß67(E11)Val → Gly; HBB: c.203T>G]: the role of genetic testing in the diagnosis of idiopathic hemolytic anemia.

The increasing availability of DNA sequencing of globin genes has improved our ability to detect conditions that were presumed to be extremely rare. These conditions may remain undiagnosed due to unfamiliarity with clinical presentation, relative unavailability of advanced diagnostic alternatives, or may defy detection by being electrophoretically silent or extreme instability rendering their presence to be below detection level. Genetic studies were pursued in a mother and daughter with severe hemolytic anemia as initial testing failed to be diagnostic. DNA sequence analysis of the ß-globin gene identified Hb Manukau [ß67(E11)Val → Gly; HBB: c.203T > G], an extremely unstable hemoglobin (Hb) variant. This is the second family described with this condition (first in the western hemisphere). An astute clinician may benefit from being persistent and pursuing additional testing including molecular genetic characterization where clinical suspicion remains high.

Addressing dental fear in children with autism spectrum disorders: a randomized controlled pilot study using electronic screen media.

BACKGROUND: Dental care is a significant unmet health care need for children with autism spectrum disorders (ASD). Many children with ASD do not receive dental care because of fear associated with dental procedures; oftentimes they require general anesthesia for regular dental procedures, placing them at risk of associated complications. Many children with ASD have a strong preference for visual stimuli, particularly electronic screen media. The use of visual teaching materials is a fundamental principle in designing educational programs for children with ASD. PURPOSE: To determine if an innovative strategy using 2 types of electronic screen media was feasible and beneficial in reducing fear and uncooperative behaviors in children with ASD undergoing dental visits. METHODS: We conducted a randomized controlled trial at Boston Children's Hospital dental clinic. Eighty (80) children aged 7 to 17 years with a known diagnosis of ASD and history of dental fear were enrolled in the study. Each child completed 2 preventive dental visits that were scheduled 6 months apart (visit 1 and visit 2). After visit 1, subjects were randomly assigned to 1 of 4 groups: (1) group A, control (usual care); (2) group B, treatment (video peer modeling that involved watching a DVD recording of a typically developing child undergoing a dental visit); (3) group C, treatment (video goggles that involved watching a favorite movie during the dental visit using sunglass-style video eyewear); and (4) group D, treatment (video peer modeling plus video goggles). Subjects who refused or were unable to wear the goggles watched the movie using a handheld portable DVD player. During both visits, the subject's level of anxiety and behavior were measured using the Venham Anxiety and Behavior Scales. Analyses of variance and Fisher's exact tests compared baseline characteristics across groups. Using intention to treat approach, repeated measures analyses were employed to test whether the outcomes differed significantly: (1) between visits 1 and 2 within each group and (2) between each intervention group and the control group over time (an interaction). RESULTS: Between visits 1 and 2, mean anxiety and behavior scores decreased significantly by 0.8 points (P = .03) for subjects within groups C and D. Significant changes were not observed within groups A and B. Mean anxiety and behavior scores did not differ significantly between groups over time, although group A versus C pairwise comparisons showed a trend toward significance (P = .06). CONCLUSION: These findings suggest that certain electronic screen media technologies may be useful tools for reducing fear and uncooperative behaviors among children with ASD undergoing dental visits. Further studies are needed to assess the efficacy of these strategies using larger sample sizes. Findings from future studies could be relevant for nondental providers who care for children with ASD in other medical settings.

Early performance in a humanistic medicine course as a predictor of dental students' later clinical performance.

The purpose of this study was to test the hypothesis that dental students' early ability to demonstrate a humanistic approach with patients is associated with later clinical performance. A first-year humanistic medicine course, Patient Doctor I (PDI), at Harvard School of Dental Medicine combines training in conducting the medical interview with human values, placing a high value on strengthening relationships with patients and emphasizing empowerment, respect, and strong communication skills. Retrospective data were collected in the following domains: PDI course evaluations, admissions information, National Board Dental Examination Parts I and II scores, and Promotions Committee and faculty evaluation scores for hand skills and humanistic and interactive patient-student skills. Planned linear contrasts comparisons were performed for each clinical outcome variable. Tests to support the a priori hypothesis of linear relationships between PDI evaluation ratings and clinical performance, defined as hand skills and humanistic and interactive patient-student skills scores, were significant, both at p=0.03. This study demonstrated the feasibility of measuring dental students' humanistic qualities during the first year. Humanistic qualities (PDI performance) during the first year were found to be associated with clinical performance in the third year of dental school.

A performance measurement plan for pediatric dentists: using accuracy of caries diagnosis from intraoral radiographs.

PURPOSE: The purpose of this study was to develop a metric for measuring (1) an individual pediatric dentist's performance against peer performance and (2) aggregate group performance, using accuracy of caries diagnosis. METHODS: A total of 3,985 tooth surfaces (from 174 patients) on intraoral bitewing radiographs were assessed by 9 precalibrated attending pediatric dentists at Children's Hospital Boston over a 3-year period. Each surface was reviewed by 3 pediatric dentists (the operating dentist and 2 peer reviewers) using a score card. An accurate diagnosis was defined as agreement between the operating dentist and at least 1 peer reviewer as to the presence or absence of caries. RESULTS: Average percentage diagnostic accuracy within the group over the course of the project was approximately 95% (95% confidence interval=94.0-95.4). Individual dentist scores ranged from approximately 89% to 96%. Group average rose steadily over time, from approximately 93% in 2008 to 97% by 2010. Unacceptable diagnosis (∼5% of surfaces assessed) did not directly translate into unfavorable treatment (∼4% of surfaces with unacceptable diagnosis). CONCLUSIONS: Interexaminer reliability as a proxy for accuracy of caries diagnoses from bitewing radiographs is a viable metric for improving and assessing the quality of care provided by pediatric dentists.

Cryoballoon ablation of pulmonary veins for paroxysmal atrial fibrillation: first results of the North American Arctic Front (STOP AF) pivotal trial.

OBJECTIVES: This study sought to assess the safety and effectiveness of a novel cryoballoon ablation technology designed to achieve single-delivery pulmonary vein (PV) isolation. BACKGROUND: Standard radiofrequency ablation is effective in eliminating atrial fibrillation (AF) but requires multiple lesion delivery at the risk of significant complications. METHODS: Patients with documented symptomatic paroxysmal AF and previously failed therapy with ≥ 1 membrane active antiarrhythmic drug underwent 2:1 randomization to either cryoballoon ablation (n = 163) or drug therapy (n = 82). A 90-day blanking period allowed for optimization of antiarrhythmic drug therapy and reablation if necessary. Effectiveness of the cryoablation procedure versus drug therapy was determined at 12 months. RESULTS: Patients had highly symptomatic AF (78% paroxysmal, 22% early persistent) and experienced failure of at least one antiarrhythmic drug. Cryoablation produced acute isolation of three or more PVs in 98.2% and all four PVs in 97.6% of patients. PVs isolation was achieved with the balloon catheter alone in 83%. At 12 months, treatment success was 69.9% (114 of 163) of cryoblation patients compared with 7.3% of antiarrhythmic drug patients (absolute difference, 62.6% [p < 0.001]). Sixty-five (79%) drug-treated patients crossed over to cryoablation during 12 months of study follow-up due to recurrent, symptomatic AF, constituting drug treatment failure. There were 7 of the resulting 228 cryoablated patients (3.1%) with a >75% reduction in PV area during 12 months of follow-up. Twenty-nine of 259 procedures (11.2%) were associated with phrenic nerve palsy as determined by radiographic screening; 25 of these had resolved by 12 months. Cryoablation patients had significantly improved symptoms at 12 months. CONCLUSIONS: The STOP AF trial demonstrated that cryoballoon ablation is a safe and effective alternative to antiarrhythmic medication for the treatment of patients with symptomatic paroxysmal AF, for whom at least one antiarrhythmic drug has failed, with risks within accepted standards for ablation therapy. (A Clinical Study of the Arctic Front Cryoablation Balloon for the Treatment of Paroxysmal Atrial Fibrillation [Stop AF]; NCT00523978).

Assessing early performance in the patient-doctor relationship in dental education.

In addition to current admissions criteria, the assessment of qualities related to humanistic medicine may help predict clinical and academic performance in dental education. The objective of this feasibility study was to develop and assess the reliability of a coding scheme to quantify and rate qualitative formative narratives describing individual student performance in a medical interview course that utilizes principles of humanistic medicine. A mixed method, using focus groups and individual interviews, was used to develop a coding strategy. Three coders retrospectively rated 209 formative narratives evaluating first-year students at the Harvard School of Dental Medicine to determine high and low performance in this course. Interrater reliability was tested. The focus groups yielded the use of superlatives to identify high performance, with their absence indicating low performance. This study found a high level of calibration among independent coders (Cronbach's alpha 0.75). Twenty-four (11.5 percent) of the narrative evaluations were coded as "high performers" and seven (3.3 percent) as "low performers." The results demonstrate the feasibility of quantifying narrative evaluations to determine high and low performance in a patient-centered course for dental students. It may be that humanistic qualities taught in a patient-centered medical interview course are more significant competencies than previously thought.

Prevalence of 2009 pandemic influenza A (H1N1) virus antibodies, Tampa Bay Florida--November-December, 2009.

BACKGROUND: In 2009, a novel influenza virus (2009 pandemic influenza A (H1N1) virus (pH1N1)) caused significant disease in the United States. Most states, including Florida, experienced a large fall wave of disease from September through November, after which disease activity decreased substantially. We determined the prevalence of antibodies due to the pH1N1 virus in Florida after influenza activity had peaked and estimated the proportion of the population infected with pH1N1 virus during the pandemic. METHODS: During November-December 2009, we collected leftover serum from a blood bank, a pediatric children's hospital and a pediatric outpatient clinic in Tampa Bay Florida. Serum was tested for pH1N1 virus antibodies using the hemagglutination-inhibition (HI) assay. HI titers ≥40 were considered seropositive. We adjusted seroprevalence results to account for previously established HI assay specificity and sensitivity and employed a simple statistical model to estimate the proportion of seropositivity due to pH1N1 virus infection and vaccination. RESULTS: During the study time period, the overall seroprevalence in Tampa Bay, Florida was 25%, increasing to 30% after adjusting for HI assay sensitivity and specificity. We estimated that 5.9% of the population had vaccine-induced seropositivity while 25% had seropositivity secondary to pH1N1 virus infection. The highest cumulative incidence of pH1N1 virus infection was among children aged 5-17 years (53%) and young adults aged 18-24 years (47%), while adults aged ≥50 years had the lowest cumulative incidence (11-13%) of pH1N1 virus infection. CONCLUSIONS: After the peak of the fall wave of the pandemic, an estimated one quarter of the Tampa Bay population had been infected with the pH1N1 virus. Consistent with epidemiologic trends observed during the pandemic, the highest burdens of disease were among school-aged children and young adults.

Positron emission tomography of brain ß-amyloid and τ levels in adults with Down syndrome.

OBJECTIVES: To determine the neuropathological load in the living brain of nondemented adults with Down syndrome using positron emission tomography with 2-(1-{6-[(2-fluorine 18-labeled fluoroethyl)methylamino]-2-napthyl}ethylidene) malononitrile ([(18)F]FDDNP) and to assess the influence of age and cognitive and behavioral functioning. For reference, [(18)F]FDDNP binding values and patterns were compared with those from patients with Alzheimer disease and cognitively intact control participants. DESIGN: Cross-sectional clinical study. PARTICIPANTS: Volunteer sample of 19 persons with Down syndrome without dementia (mean age, 36.7 years), 10 patients with Alzheimer disease (mean age, 66.5 years), and 10 controls (mean age, 43.8 years). MAIN OUTCOME MEASURES: Binding of [(18)F]FDDNP in brain regions of interest, including the parietal, medial temporal, lateral temporal, and frontal lobes and posterior cingulate gyrus, and the average of all regions (global binding). RESULTS: The [(18)F]FDDNP binding values were higher in all brain regions in the Down syndrome group than in controls. Compared with the Alzheimer disease group, the Down syndrome group had higher [(18)F]FDDNP binding values in the parietal and frontal regions, whereas binding levels in other regions were comparable. Within the Down syndrome group, age correlated with [(18)F]FDDNP binding values in all regions except the posterior cingulate, and several measures of behavioral dysfunction showed positive correlations with global, frontal, parietal, and posterior cingulate [(18)F]FDDNP binding. CONCLUSIONS: Consistent with neuropathological findings from postmortem studies, [(18)F]FDDNP positron emission tomography shows high binding levels in Down syndrome comparable to Alzheimer disease and greater levels than in members of a control group. The positive associations between [(18)F]FDDNP binding levels and age as well as behavioral dysfunction in Down syndrome are consistent with the age-related progression of Alzheimer-type neuropathological findings in this population.

Unmet dental needs and barriers to care for children with significant special health care needs.

PURPOSE: The purpose of this study was to conduct the first known large scale survey of parents of children with special health care needs (CSHCN) to determine their child's: oral health status; access to dental care; perceived barriers (environmental/system and nonenvironmental/family); and oral health quality of life, accounting for each child's medical diagnosis and severity of diagnosis. METHODS: A 72-item survey was sent to 3760 families of CSHCN throughout urban and rural Massachusetts. RESULTS: The study yielded 1,128 completed surveys. More than 90% of the children had seen a dentist within the past year; 66% saw a pediatric dentist, and 21% needed intense behavioral interventions. Although most families had high education levels, private dental insurance, and above average incomes, 20% of CSHCN had an unmet dental need. Children with craniofacial anomalies had twice as many unmet needs and children with cystic fibrosis had fewer unmet needs. Children with cerebral palsy, autism, developmental delay, and Down syndrome had more aversions to dental treatment, more treatment complications posed by their medical conditions, and more difficulty finding a dentist willing to provide care. Children with cystic fibrosis, metabolic disorders, or hemophilia encountered fewer barriers to care. CONCLUSIONS: The data paint a picture of high unmet dental needs with subpopulations of children with special health care needs who are more at risk for system barriers and internal family barriers to care based on their medical diagnoses.

Dental manifestations associated with Seckel syndrome type II: a case report.

Seckel syndrome is a rare form of primordial dwarfism that is characterized by short stature, skeletal defects, mental retardation, and characteristic facial features such as microcephaly, micrognathia, and a bird-head appearance. Dental findings include hypodontia, enamel hypoplasia, crowding, and Class II malocclusion. The purpose of this paper was to report the case of a female patient with Seckel syndrome type II and describe her orodental manifestations. She presented with interesting dental findings, including gingival hyperplasia, recession and ulceration, significant crowding, and early exfoliation of the primary dentition with accelerated eruption of the permanent dentition. The patient received comprehensive dental care under general anesthesia, and hard and soft tissue samples were collected for histologic analysis. The patient was followed for over 3 years.

Results of the Prospective Minnesota Study of ECHO/TDI in Cardiac Resynchronization Therapy (PROMISE-CRT) study.

BACKGROUND: Retrospective single-center studies have shown that measures of mechanical dyssynchrony before cardiac resynchronization therapy (CRT), or acute changes after CRT, predict response better than QRS duration. The Prospective Minnesota Study of Echocardiographic/TDI in Cardiac Resynchronization Therapy (PROMISE-CRT) study was a prospective multicenter study designed to determine whether acute (1 week) changes in mechanical dyssynchrony were associated with response to CRT. METHODS AND RESULTS: Nine Minnesota Heart Failure Consortium centers enrolled 71 patients with standard indications for CRT. Left ventricular (LV) size, function, and mechanical dyssynchrony (echocardiography [ECHO], tissue Doppler imaging [TDI], speckle-tracking echocardiography [STE]) as well as 6-minute walk distance and Minnesota Living with Heart Failure Questionnaire scores were measured at baseline and 3 and 6 months after CRT. Acute change in mechanical dyssynchrony was not associated with clinical response to CRT. Acute change in STE radial dyssynchrony explained 73% of the individual variation in reverse remodeling. Baseline measures of mechanical dyssynchrony were associated with reverse remodeling (but not clinical) response, with 4 measures each explaining 12% to 30% of individual variation. CONCLUSIONS: Acute changes in radial mechanical dyssynchrony, as measured by STE, and other baseline mechanical dyssynchrony measures were associated with CRT reverse remodeling. These data support the hypothesis that acute improvement in LV mechanical dyssynchrony is an important mechanism contributing to LV reverse remodeling with CRT.

An experimental approach to detecting dementia in Down syndrome: a paradigm for Alzheimer's disease.

Measures developed from animal models of aging may detect dementia of the Alzheimer's type in a population at-risk for Alzheimer's disease (AD). Although, by middle age, individuals with Down syndrome (DS) show an extraordinarily high prevalence of AD-type pathology, their severe idiopathic cognitive deficits tend to confound the clinical diagnosis of AD. The current study was designed to improve detection of AD in DS by using measures of learning and memory derived from animal models of aging. Adults with DS (N=34) were assessed and reassessed (n=19) approximately one year later using stimulus-response (S-R) test methods derived from experimental literature, as well as standardized informant-based tests. Results demonstrated high validity and reliability of select tests. The implication of early symptom detection in a population at-risk for AD-type dementia was discussed in terms of potential brain regions of interest.

Impact of acute rotavirus gastroenteritis on pediatric outpatient practices in the United States.

OBJECTIVES: The objectives of this study were to determine the presenting symptoms, healthcare utilization, and lost time from work and day care associated with acute rotavirus gastroenteritis. METHODS: During the winter to spring seasons of 2002-2003 or 2003-2004, children <36 months of age presenting with acute gastroenteritis to urban and suburban pediatric outpatient practices affiliated with 5 academic centers across the United States were enrolled in similarly designed studies. The case definition required >or=3 watery or looser-than-normal stools and/or forceful vomiting within a 24-hour period beginning