Search

Background Retaining participants over time is a frequent challenge in research studies evaluating long-term health outcomes. This study’s objective was to compare the impact of prepaid and postpaid incentives on response to a six-month follow-up survey. Methods We conducted an experiment to compare response between participants randomized to receive either prepaid or postpaid cash card incentives within a multisite study of children under 15 years in age who were hospitalized for a serious, severe, or critical injury. Participants were parents or guardians of enrolled children. The primary outcome was survey response. We also examined whether demographic characteristics were associated with response and if incentive timing influenced the relationship between demographic characteristics and response. We evaluated whether incentive timing was associated with the number of calls needed for contact. Results The study enrolled 427 children, and parents of 420 children were included in this analysis. Follow-up survey response did not differ according to the assigned treatment arm, with the percentage of parents responding to the survey being 68.1% for the prepaid incentive and 66.7% with the postpaid incentive. Likelihood of response varied by demographics. Spanish-speaking parents and parents with lower income and lower educational attainment were less likely to respond. Parents of Hispanic/Latino children and children with Medicaid insurance were also less likely to respond. We found no relationship between the assigned incentive treatment and the demographics of respondents compared to non-respondents. Conclusions Prepaid and postpaid incentives can obtain similar participation in longitudinal pediatric critical care outcomes research. Incentives alone do not ensure retention of all demographic subgroups. Strategies for improving representation of hard-to-reach populations are needed to address health disparities and ensure the generalizability of studies using these results.

OBJECTIVE: We evaluated the acceptability of the Pediatric Quality of Life Inventory (PedsQL) and other outcomes as the primary outcomes for a pediatric hemorrhagic trauma trial (TIC-TOC) among clinicians. METHODS: We conducted a mixed-methods study that included an electronic questionnaire followed by teleconference discussions. Participants confirmed or rejected the PedsQL as the primary outcome for the TIC-TOC trial and evaluated and proposed alternative primary outcomes. Responses were compiled and a list of themes and representative quotes was generated. RESULTS: 73 of 91 (80%) participants completed the questionnaire. 61 (84%) participants agreed that the PedsQL is an appropriate primary outcome for children with hemorrhagic brain injuries. 32 (44%) participants agreed that the PedsQL is an acceptable primary outcome for children with hemorrhagic torso injuries, 27 (38%) participants were neutral, and 13 (18%) participants disagreed. Several themes were identified from responses, including that the PedsQL is an important and patient-centered outcome but may be affected by other factors, and that intracranial hemorrhage progression assessed by brain imaging (among patients with brain injuries) or blood product transfusion requirements (among patients with torso injuries) may be more objective outcomes than the PedsQL. CONCLUSIONS: The PedsQL was a well-accepted proposed primary outcome for children with hemorrhagic brain injuries. Traumatic intracranial hemorrhage progression was favored by a subset of clinicians. A plurality of participants also considered the PedsQL an acceptable outcome for selection for pediatric trauma clinical trial children with hemorrhagic torso injuries. Blood product transfusion requirement was favored by fewer participants.

PurposeFunctional outcomes have been proposed for assessing quality of pediatric trauma care. Outcomes assessments often rely on Abbreviated Injury Scale (AIS) severity scores to adjust for injury characteristics, but the relationship between AIS severity and functional impairment is unknown. This study's primary aim was to quantify functional impairment associated with increasing AIS severity scores within body regions. The secondary aim was to assess differences in impairment between body regions based on AIS severity.MethodsChildren with serious (AIS≥3) isolated body region injuries enrolled in a multicenter prospective study were analyzed. The primary outcome was functional status at discharge measured using the Functional Status Scale (FSS). Discharge FSS was compared (1) within each body region across increasing AIS severity scores, and (2) between body regions for injuries with matching AIS scores.ResultsThe study included 266 children, with 16% having abnormal FSS at discharge. Worse FSS was associated with increasing AIS severity only for spine injuries. Abnormal FSS was observed in a greater proportion of head injury patients with a severely impaired initial Glasgow Coma Scale (GCS) (GCS

The objective of this analysis is to examine whether the severity of systemic sclerosis (SSc)-hand involvement influences patient-reported outcome measure (PROM) completion rate in a US cohort of early disease. Participants included SSc patients with less than 5 years disease duration consented and enrolled in the Collaborative, National, Quality, and Efficacy Registry (CONQUER) between June 2018 and December 2019. Participants' socio-demographics, hand clinical features (severe modified Rodnan skin score, presence of small joint contractures, acro-osteolysis, calcinosis, and digital ulcers), and completion rates of seven PROMs including a Resource Use Questionnaire were analyzed. Cohort characteristics and baseline PROM completion were evaluated. Multivariable logistic regression assessed the relationship between hand limitations and PROM incompletion at several time points using generalized estimating equations. At the time of data lock, 339 CONQUER subjects had a total of 600 visits available for analysis. Calcinosis (odds ratio [OR] 6.35, confidence interval [CI] 2.41-16.73 and acro-osteolysis OR 3.88 (1.57-9.55) were significantly associated with incomplete PROM. The Resource Use Questionnaire was the PROM most commonly not completed. Increasing age was correlated with resource use questionnaire incompletion rate. Acro-osteolysis and calcinosis were associated with lower PROM completion rates in a US SSc cohort, independent of the length of the questionnaires or the modality of administration (electronic or paper). Resource Use Questionnaires are important for understanding the economic impact and burden of chronic disease; however, in this study, it had lower completion rates than PROMs devoted to clinical variables. Key points •Multiple strategies are needed to ensure optimal completion of PROM in longitudinal cohort studies. Even if patients request electronic surveys, we have found it is important to follow up incomplete surveys with paper forms provided at the time of a clinical visit. •The Resource Utilization Questionnaire was lengthy and prone to non-completion in the younger population. •Acro-osteolysis and calcinosis were associated with reduced PROM completion rates.

Nonadherence in clinical trials affects safety and efficacy determinations. Predictors of nonadherence in pediatric acute illness trials are unknown. We sought to examine predictors of nonadherence in a multicenter randomized trial of 971 children with acute gastroenteritis receiving a 5-day oral course of Lactobacillus rhamnosus GG or placebo. Adherence, defined as consuming all doses of the product, was reported by the parents and recorded during daily follow-up contacts. Of 943 patients with follow-up data, 766 (81.2%) were adherent. On multivariate analysis, older age (OR 1.19; 95% CI: 1.00-1.43), increased vomiting duration (OR 1.23; 95% CI: 1.05-1.45), higher dehydration score (OR 1.23, 95% CI: 1.07-1.42), and hospitalization following ED discharge (OR 4.16, 95% CI: 1.21--14.30) were factors associated with nonadherence; however, those with highest severity scores were more likely to adhere (OR 0.87, 95% CI: 0.80-0.95). These data may inform strategies and specific targets to maximize adherence in future pediatric trials.

AIM Interstitial lung disease (ILD) is the leading cause of disease-related death in systemic sclerosis (SSc). Here, we assess baseline characteristics of SSc subjects with and without restrictive lung disease (RLD) in a multi-center, US-based registry. METHODS SSc patients within 5 years of disease onset were enrolled in the Collaborative National Quality and Efficacy Registry (CONQUER), a multi-center US-based registry of SSc study participants (age ≥ 18 years) enrolled at 13 expert centers. All subjects met 2013 American College of Rheumatology / European League Against Rheumatism criteria. Subjects with a pulmonary function test (PFT) at baseline before April 1, 2020 were included. High-resolution computed tomography scan of the chest was not available to characterize ILD for all subjects. RLD was defined as forced vital capacity (FVC)

Background It is unknown if probiotics exert pathogen-specific effects in children with diarrhea secondary to acute gastroenteritis. Methods Analysis of patient-level data from 2 multicenter randomized, placebo controlled trials conducted in pediatric emergency departments in Canada and the United States. Participants were 3–48 months with >3 diarrheal episodes in the preceding 24 hours and were symptomatic for Results Pathogens were identified in specimens from 59.3% of children (928/1565). No pathogen groups were less likely to experience an MVS score ≥9 based on treatment allocation (test for interaction = 0.35). No differences between groups were identified for adenovirus (adjusted relative risk [aRR]: 1.42; 95% confidence interval [CI]: .62, 3.23), norovirus (aRR: 0.98; 95% CI: .56, 1.74), rotavirus (aRR: 0.86; 95% CI: .43, 1.71) or bacteria (aRR: 1.19; 95% CI: .41, 3.43). At pathogen-group and among individual pathogens there were no differences in diarrhea duration or the total number of diarrheal stools between treatment groups, regardless of intervention allocation or among probiotic sub-groups. Among adenovirus-infected children, those administered the L. rhamnosus R0011/L. helveticus R0052 product experienced fewer diarrheal episodes (aRR: 0.65; 95% CI: .47, .90). Conclusions Neither probiotic product resulted in less severe disease compared to placebo across a range of the most common etiologic pathogens. The preponderance of evidence does not support the notion that there are pathogen specific benefits associated with probiotic use in children with acute gastroenteritis. Clinical Trials Registration NCT01773967 and NCT01853124.

Objective The study aimed to determine if a program of mid-trimester serum proteomics screening of women at low risk for spontaneous preterm birth (sPTB) and the use of a PTB risk-reduction protocol in those whose results indicated an increased risk of sPTB would reduce the likelihood of sPTB and its sequelae. Study Design Prospective comparison of birth outcomes in singleton pregnancies with mid-trimester cervical length ≥2.5 cm and at otherwise low risk for sPTB randomized to undergo or not undergo mid-trimester serum proteomics screening for increased risk of sPTB (NCT 03530332). Screen-positive women were offered a group of interventions aimed at reducing the risk of spontaneous PTB. The primary outcome was the rate of sPTB Results A total of 1,191 women were randomized. Screened and unscreened women were demographically similar. sPTB Conclusion Mid-trimester serum proteomics screening of women at low risk for sPTB and the use of a sPTB risk-reduction protocol in screen-positive patients did not significantly reduce the rate of sPTB compared with women not screened, though the trial was underpowered thus limiting the interpretation of negative findings. Infants in the screened group had a significantly shorter NICU LOS, a difference likely due to a reduced number of infants in the screened group that delivered Key Points

The Collaborative National Quality and Efficacy Registry (CONQUER) for Scleroderma is a multicenter US-based longitudinal study of patients with systemic sclerosis (SSc) within 5 years of first non-Raynaud’s symptom. The data collection methodology incorporates successful models from other SSc registries. The cohort is designed to provide linked bio-specimen and clinical outcomes data on a longitudinal cohort of SSc patients for validation of hypothesis-driven research and to provide a platform for studying patient-reported outcomes in scleroderma. The CONQUER registry was developed using the guidelines of the International Society for Biological Repositories, and was an iterative process between physicians with an expertise in SSc, patient stakeholders, and information technology experts. Enrollment commenced in June 2018. During the first 6 months of the CONQUER Scleroderma study, 151 SSc patients with less than 5 years of disease duration (from first non-Raynaud’s symptom) have been recruited. The mean age is 51 ± 14 years, 83% are female, and 60% of patients have diffuse disease. Survey completion rates are above 88% for all patient-reported outcome surveys. Bio-specimen collection rates are over 97%, and disease severity score completion rates are over 98%. Pulmonary function test data is available on 91% of patients, and echocardiography is available 80%. The CONQUER scleroderma study provides a unique and growing resource for studying scleroderma in a longitudinal, US-based population. • The Collaborative National Quality and Efficacy Registry (CONQUER) for Scleroderma is a multicenter US-based longitudinal study of patients with systemic sclerosis (SSc) within 5 years of first non-Raynaud’s symptom. • The CONQUER scleroderma study provides a unique and growing resource for studying scleroderma in a longitudinal, US-based population. • CONQUER is innovative in its design in that it is focused on prospective collection of paired clinical and patient outcome data with bio-specimens.

Tranexamic acid improves survival in severely injured adults. However, its effectiveness on overall functional outcome is unknown. We hypothesized that tranexamic acid improves overall functional outcome compared with placebo in severely injured adults and conduct an exploratory analysis of the Clinical Randomization of an Antifibrinolytic in Significant Haemorrhage (CRASH-2) data to investigate this hypothesis.We included injured adults from the CRASH-2 trial who were randomized 3 hours or less from injury. The primary outcome measure was functional status at hospital discharge or on day 28 if the subject was still in the hospital. Functional status was measured with the modified Oxford Handicap Scale, a 6-category ordinal functional outcome scale. We conducted 3 separate analyses using 3 different outcome measures to evaluate the effectiveness of tranexamic acid versus placebo on functional outcomes, including the mean utility-weighted modified Oxford Handicap Scale score (overall functional outcome), the area under the curve (based on functional outcome and rate of recovery), and a sliding dichotomy analysis (favorable versus unfavorable functional outcome) stratified by baseline mortality risk (stratified analysis).There were 13,432 patients (6,679 randomized to placebo and 6,753 to tranexamic acid) included in the study cohort. The mean utility-weighted modified Oxford Handicap Scale score was 0.66 (SD 0.33) for patients randomized to tranexamic acid compared with a mean of 0.64 (SD 0.34) for those randomized to placebo (mean difference 0.02; 95% confidence interval [CI] 0.01 to 0.03). The area under the curve analysis demonstrated that patients randomized to tranexamic acid had a higher 28-day mean utility-weighted modified Oxford Handicap Scale score compared with those randomized to placebo (mean score 0.55 [SD 0.30] versus 0.53 [SD 0.31]; mean difference 0.02 [95% CI 0.01 to 0.03]). The sliding dichotomy analysis demonstrated heterogeneity of treatment effects across risk groups. The overall proportion of patients with favorable functional outcomes was higher in the tranexamic acid group (5,360/6,753 [79.4%]; 95% CI 78.4% to 80.3%) compared with the placebo group (5,174/6,679 [77.5%]; 95% CI 76.5% to 78.5%; difference 1.9% [95% CI 0.5% to 3.3%]; number needed to treat=52). When each risk group was tested separately, only the lowest-risk group (6% baseline mortality risk) demonstrated a statistically significant effect of tranexamic acid toward favorable functional outcomes (tranexamic acid versus placebo adjusted odds ratio 0.78; 95% CI 0.67 to 0.90). There were no differences between tranexamic acid and placebo in the other risk groups.Across 3 exploratory analyses, severely injured adult patients randomized within 3 hours from injury demonstrated better functional outcomes with tranexamic acid compared with placebo. When heterogeneity of treatment effects across risk groups was evaluated, only the lowest-risk group demonstrated a significant effect of tranexamic acid toward favorable outcomes. Given the overall safety and cost-effectiveness of tranexamic acid use in injured adults, our results further support the use of tranexamic acid for this population. Future trauma trials that evaluate tranexamic acid use should also consider functional status as an important outcome.

Background Federal exception from informed consent (EFIC) procedures allow studies to enroll patients with time-sensitive, life-threatening conditions when written consent is not feasible. Our objective was to compare enrollment rates with and without EFIC in a trial of tranexamic acid (TXA) for children with hemorrhagic injuries. Methods We conducted a four-center randomized controlled pilot and feasibility trial evaluating TXA in children with severe hemorrhagic brain and/or torso injuries. We initiated the trial enrolling patients without EFIC. After 3 months of enrollment, we met our a priori futility threshold and paused the trial to incorporate EFIC procedures and obtain regulatory approval. We then restarted the trial allowing EFIC if the guardian was unable to provide timely written consent. We used descriptive statistics to compare characteristics of eligible patients approached with and without EFIC procedures. We also calculated the time delay to restart the trial using EFIC. Results We enrolled 1 of 15 (6.7%) eligible patients (0.17 per site per month) prior to using EFIC procedures. Of the 14 missed eligible patients, 7 (50%) were not enrolled because guardians were not present or were injured and unable to provide written consent. After obtaining approval for EFIC, we enrolled 30 of 48 (62.5%) eligible patients (1.34 per site per month). Of these 30 patients, 22 (73.3%) were enrolled with EFIC. Of the 22, no guardians refused written consent after randomization. There were no significant differences in the eligibility rate and patient characteristics enrolled with and without EFIC procedures. Across all sites, the mean delay to restart the trial using EFIC procedures was 12 months. Conclusions In a multicenter trial of severely injured children, the use of EFIC procedures greatly increased the enrollment rate and was well accepted by guardians. Initiating the trial without EFIC procedures led to a significant delay in enrollment.

Background While using an inhaled corticosteroid (ICS) in the weeks after an ED visit reduces repeat visits, few children receive a needed prescription. Because a prescription may not be filled or used, dispensing ICS at discharge and supervising its use at school could overcome both barriers until follow-up care is established. To assess the feasibility of such an intervention, we conducted a pilot study among elementary-age school children with persistent asthma who were discharged from the ED following an asthma exacerbation. Methods Eligible children were randomly assigned to ED-dispensing of ICS with home supervision or ED-dispensing of ICS with home and school supervision. The primary outcomes were ability to recruit and retain participants, ability to initiate school-supervised medication administration within 5 days of discharge, and participant satisfaction. Results Despite identifying 437 potentially eligible children, only 13 (3%) were enrolled with 6 being randomized to the intervention group and 7 to the control group. Eleven (85%) randomized participants completed the 90-day interview (primary outcome) and 8 (62%) completed the 120-day interview (safety endpoint). Four (67%) intervention participants started their school regimen within 5 business days and 2 started within 6 business days. Conclusion While our pilot study did not meet its recruitment goal, it did achieve its primary purpose of assessing feasibility before undertaking a larger, more intensive study. Several major recruitment barriers need to be mitigated before EDs can successfully partner with schools to establish supervised ICS treatment. Trial registration ClinicalTrials.gov, NCT03952286. Registered 16 May 2019

BACKGROUND Children with abusive injuries have worse mortality, length-of-stay, complications, and healthcare costs compared to those sustaining an accidental injury. Long-term functional impairment is common in children with abusive head trauma but has not been examined in a cohort with heterogeneous body region injuries. OBJECTIVE To assess for an independent association between child physical abuse and functional impairment at discharge and six-month follow-up. PARTICIPANTS AND SETTING Seriously injured children (

Background Disability and impaired health-related quality of life can persist for months among injured children. Previous studies of long-term outcomes have focused mainly on children with specific injury types rather than those with multiple injured body regions. This study's objective was to determine the long-term functional status and health-related quality of life after serious pediatric injury, and to evaluate the associations of these outcomes with features available at hospital discharge. Study Design We conducted a prospective observational study at 7 Level I pediatric trauma centers of children treated for at least 1 serious (Abbreviated Injury Scale severity 3 or higher) injury. Patients were sampled to increase the representation of less frequently injured body regions and multiple injured body regions. Six-month functional status was measured using the Functional Status Scale (FSS) and health-related quality of life using the Pediatric Quality of Life Inventory. Results Among 323 injured children with complete discharge and follow-up assessments, 6-month FSS score was abnormal in 33 patients (10.2%)—16 with persistent impairments and 17 previously normal at discharge. Increasing levels of impaired discharge FSS score were associated with impaired FSS and lower Pediatric Quality of Life Inventory scores at 6-month follow-up. Additional factors on multivariable analysis associated with 6-month FSS impairment included older age, penetrating injury type, severe head injuries, and spine injuries, and included older age for lower 6-month Pediatric Quality of Life Inventory scores. Conclusions Older age and discharge functional status are associated with long-term impairment of functional status and health-related quality of life. Although most seriously injured children return to normal, ongoing disability and reduced health-related quality of life remained 6 months after injury. Our findings support long-term assessments as standard practice for evaluating the health impacts of serious pediatric injury.

BACKGROUND: Between-country variation in health care resource use and its impact on outcomes in acute care settings have been challenging to disentangle from illness severity by using administrative data. METHODS: We conducted a preplanned analysis employing patient-level emergency department (ED) data from children enrolled in 2 previously conducted clinical trials. Participants aged 3 to RESULTS: In adjusted analysis, unscheduled revisits within 7 days did not differ (adjusted odds ratio [aOR]: 0.72; 95% confidence interval (CI): 0.50 to 1.02). At the index ED visit, although participants in Canada were assessed as being more dehydrated, intravenous fluids were administered more frequently in the United States (aOR: 4.6; 95% CI: 2.9 to 7.1). Intravenous fluid administration rates did not differ after enrollment (aOR: 1.4; 95% CI: 0.7 to 2.8; US cohort with Canadian as referent). Overall, intravenous rehydration was higher in the United States (aOR: 3.8; 95% CI: 2.5 to 5.7). Although hospitalization rates during the 7 days after enrollment (aOR: 1.1; 95% CI: 0.4 to 2.6) did not differ, hospitalization at the index visit was more common in the United States (3.9% vs 2.3%; aOR: 3.2; 95% CI: 1.6 to 6.8). CONCLUSIONS: Among children with gastroenteritis and similar disease severity, revisit rates were similar in our 2 study cohorts, despite lower rates of intravenous rehydration and hospitalization in Canadian-based EDs.

Background: Urinary tract infections (UTIs) are the most common serious bacterial infection in young febrile infants, and the urinalysis (UA) is an accurate screening test for emergency department (ED) evaluation. Precise estimates of risk of concomitant bacteremia and/or bacterial meningitis (invasive bacterial infections; IBI) in febrile infants ≤ 60 days have been based on presence of UTIs rather than positive UAs, and lack large prospective study. Objective: We sought to determine the prevalence of IBIs in febrile infants 0-28 …

OBJECTIVES: To determine the time to positivity for bacterial pathogens and contaminants in blood and cerebrospinal fluid (CSF) cultures in a cohort of febrile infants ≤60 days of age. METHODS: This was a secondary analysis of prospective observational multicenter study of noncritically ill infants ≤60 days of age with temperatures ≥38°C and blood cultures (December 2008 to May 2013). The main outcome was time to positivity for bacterial pathogens and contaminants. RESULTS: A total of 256 of 303 (84.49%) patients with positive blood cultures, and 73 of 88 (82.95%) with positive CSF cultures met inclusion criteria. Median time (interquartile range [IQR]) to positivity for blood cultures was 16.6 hours (IQR 12.6–21.9) for bacterial pathogens (n = 74) and 25.1 hours (IQR 19.8–33.0) for contaminants (n = 182); P < .001. Time to bacterial pathogen positivity was similar in infants 0 to 28 days of age (15.8 hours [IQR 12.6–21.0]) and 29 to 60 days of age (17.2 [IQR 12.9–24.3]; P = .328). Median time to positivity for CSF was 14.0 hours (IQR 1.5–21.0) for bacterial pathogens (n = 22) and 40.5 hours (IQR 21.2–62.6) for contaminants (n = 51); P < .001. A total of 82.4% (95% confidence interval, 71.8–90.3) and 81.8% (95% confidence interval, 59.7%–94.8%) of blood and CSF cultures showed bacterial pathogen positivity within 24 hours. CONCLUSIONS: Among febrile infants ≤60 days of age, time to blood and CSF positivity was significantly shorter for bacterial pathogens than contaminants. Most blood and CSF cultures for bacterial pathogens were positive within 24 hours. With our findings, there is potential to reduce duration of hospitalization and avoid unnecessary antibiotics.

Objective Few prospective studies have assessed the occurrence of radiographic pneumonia in young febrile infants. We analyzed factors associated with radiographic pneumonias in febrile infants 60 days or younger evaluated in pediatric emergency departments. Study design We conducted a planned secondary analysis of a prospective cohort study within 26 emergency departments in a pediatric research network from 2008 to 2013. Febrile (≥38°C) infants 60 days or younger who received chest radiographs were included. Chest radiograph reports were categorized as "no," "possible," or "definite" pneumonia. We compared demographics, Yale Observation Scale scores (>10 implying ill appearance), laboratory markers, blood cultures, and viral testing among groups. Results Of 4778 infants, 1724 (36.1%) had chest radiographs performed; 2.7% (n = 46) had definite pneumonias, and 3.9% (n = 67) had possible pneumonias. Patients with definite (13/46 [28.3%]) or possible (15/67 [22.7%]) pneumonias more frequently had Yale Observation Scale score >10 compared with those without pneumonias (210/1611 [13.2%], P = 0.002) in univariable and multivariable analyses. Median white blood cell count (WBC), absolute neutrophil count (ANC), and procalcitonin (PCT) were higher in the definite (WBC, 11.5 [interquartile range, 9.8-15.5]; ANC, 5.0 [3.2-7.6]; PCT, 0.4 [0.2-2.1]) versus no pneumonia (WBC, 10.0 [7.6-13.3]; ANC, 3.4 [2.1-5.4]; PCT, 0.2 [0.2-0.3]; WBC, P = 0.006; ANC, P = 0.002; PCT, P = 0.046) groups, but of unclear clinical significance. There were no cases of bacteremia in the definite pneumonia group. Viral infections were more frequent in groups with definite (25/38 [65.8%]) and possible (28/55 [50.9%]) pneumonias than no pneumonias (534/1185 [45.1%], P = 0.02). Conclusions Radiographic pneumonias were uncommon, often had viruses detected, and were associated with ill appearance, but few other predictors, in febrile infants 60 days or younger.

Background: Despite the popular belief that probiotics are most efficacious when treating acute childhood diarrhea if started early and when symptoms are more severe, the data supporting these assumptions are unclear. We sought to evaluate whether the efficacy of probiotics depends on the duration and severity of diarrhea prior to treatment. Methods: This was a pre-planned secondary analysis of two randomized placebo-controlled trials in children 3-48 months of age with acute gastroenteritis, conducted in sixteen emergency departments in North America evaluating the efficacy of two probiotic products. Participants were categorized in severity groups according to the duration (< 24h, 24 – < 72h, and ≥ 72h) and the frequency of diarrhea episodes in the 24 hours (≤ 3, 4 – 5 and ≥ 6) prior to presentation. We used regression models to assess the interaction between pre-treatment diarrhea severity groups and treatment arm (probiotic or placebo) on the presence of moderate-to-severe gastroenteritis defined by a Modified Vesikari Scale score ≥9. Secondary outcomes included diarrhea frequency and duration, unscheduled healthcare provider visits and hospitalization. Findings: 1,770 children were included, 882 (50%) received a probiotic. The development of moderate-to-severe gastroenteritis symptoms following the initiation of treatment did not differ between groups [probiotic - 18.4% (162/882) vs. placebo - 18.3% (162/888); RR 1.00; 95%CI: 0.87, 1.16; P=0.95]. There was no evidence of interaction between baseline severity and treatment (P=0.61) for the primary or any of the secondary outcomes: diarrhea duration (P=0.88), maximum diarrheal episodes in a 24 hour period (P=0.87), unscheduled health care visits (P=0.21) and hospitalization (P=0.87). Interpretation: In children 3 to 48 months with acute gastroenteritis the lack of effect of probiotics is not explained by the duration of symptoms or frequency of diarrheal episodes prior to presentation. Trial Registration: Clinicaltrials.gov # NCT01773967 and # NCT01853124. Funding Statement: This work is supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD071915) and by the Canadian Institutes of Health Research (grants 286384 and 325412). Declaration of Interests: Dr. David Schnadower received in-kind study drug and placebo from iHeath Inc., however the company did not contribute financially to the study or to the investigators, and their employees do not have access study data. I-Health personnel had no role in study design, collection management, analysis and interpretation of data; nor did they have any role or authority in writing the report nor the decision to submit the trial for publication. Dr. Stephen Freedman has received in-kind (study drug and placebo) from Lallemand Health Solutions. He provides consulting services to Takeda Pharmaceutical Company, RedHill Biopharma Ltd and Eligo Bioscience S.A.S. on childhood intestinal disorders and is supported by the Alberta Children’s Hospital Foundation Professorship in Child Health and Wellness. All other authors report no relevant conflicts. Ethics Approval Statement: The studies were approved by all local Institutional Review Boards. Written informed consent was obtained from the legal guardians of all participants.

The present study evaluated the daily risk of healthcare-associated infections and sepsis (HAIS) events in pediatric intensive care unit patients with invasive devices. This was a retrospective cohort study. Invasive devices were associated with significant daily risk of HAIS (p

Objectives To assess longitudinal associations between permanent tooth caries increment and both modifiable and non-modifiable risk factors, using best subsets model selection. Methods The Iowa Fluoride Study has followed a birth cohort with standardized caries exams without radiographs of the permanent dentition conducted at about ages 9, 13, and 17 years. Questionnaires were sent semi-annually to assess fluoride exposures and intakes, select food and beverage intakes, and tooth brushing frequency. Exposure variables were averaged over ages 7-9, 11-13, and 15-17, reflecting exposure 2 years prior to the caries exam. Longitudinal models were used to relate period-specific averaged exposures and demographic variables to adjusted decayed and filled surface increments (ADJCI) (n = 392). The Akaike Information Criterion (AIC) was used to assess optimal explanatory variable combinations. Results From birth to age 9, 9-13, and 13-17 years, 24, 30, and 55 percent of subjects had positive permanent ADJCI, respectively. Ten models had AIC values within two units of the lowest AIC model and were deemed optimal based on AIC. Younger age, being male, higher mother's education, and higher brushing frequency were associated with lower caries increment in all 10 models, while milk intake was included in 3 of 10 models. Higher milk intakes were slightly associated with lower ADJCI. Conclusions With the exception of brushing frequency, modifiable risk factors under study were not significantly associated with ADJCI. When possible, researchers should consider presenting multiple models if fit criteria cannot discern among a group of optimal models.

Importance Short- and long-term functional impairment after pediatric injury may be more sensitive for measuring quality of care compared with mortality alone. The characteristics of injured children and adolescents who are at the highest risk for functional impairment are unknown. Objective To evaluate categories of injuries associated with higher prevalence of impaired functional status at hospital discharge among children and adolescents and to estimate the number of those with injuries in these categories who received treatment at pediatric trauma centers. Design, Setting, and Participants This prospective cohort study (Assessment of Functional Outcomes and Health-Related Quality of Life After Pediatric Trauma) included children and adolescents younger than 15 years who were hospitalized with at least 1 serious injury at 1 of 7 level 1 pediatric trauma centers from March 2018 to February 2020. Exposure At least 1 serious injury (Abbreviated Injury Scale score, ≥3 [scores range from 1 to 6, with higher scores indicating more severe injury]) classified into 9 categories based on the body region injured and the presence of a severe traumatic brain injury (Glasgow Coma Scale score

OBJECTIVES: This analysis examines the etiology of caries development in adolescents by using structural equation modeling to identify behavioral mediators of the relationship between socioeconomic status (SES) and caries incidence, and to investigate the role of sex on caries preventive behavior and caries. METHODS: This analysis was based on data from the Iowa Fluoride Study, a longitudinal study of a birth cohort. We hypothesized that socioeconomic status earlier in life has a direct effect on caries development and an indirect effect from improved behavioral variables – dental visit attendance, tooth brushing frequency, and percentage of beverage intake consisting of sugar-sweetened beverages – and that sex also plays a role in behavioral variables, as well as caries. A structural equation model was developed based on these hypotheses and direct and indirect standardized path coefficients were calculated, as well as their standard errors. RESULTS: Based on our proposed model, SES at birth significantly influences SES during adolescence, but not adolescent behaviors. The effect of SES during adolescence on caries in the permanent dentition is mediated by adolescent behaviors. Female participants have worse caries than male participants, despite lower self-reported percentages of sugar-sweetened beverage intake and more frequent brushing and dental attendance. CONCLUSIONS: This analysis models the relationships among known causal factors for caries and suggests that the role of SES in caries may not be as important as previously thought and different behaviors that affect oral health between males and females as well as differences in caries between the sexes could begin during adolescence. These findings could help improve caries prevention programs for adolescents.

Instructional technologists and faculty in post-secondary institutions have increasingly adopted learning analytics interventions such as dashboards that provide real-time feedback to students to support student’ ability to regulate their learning. But analyses of the effectiveness of such interventions can be confounded by measures of students’ prior learning as well as their baseline level of self-regulated learning. For this research study, we sought to examine whether the frequency of accessing a dashboard was associated with learning outcomes after matching subjects on confounding variables. And because prior research has suggested that measures of prior learning are associated with students’ likelihood to use learning analytics interventions, we sought to adequately control for learners’ likelihood to access the feedback by using a propensity score matching with a non-binary treatment variable. We administered the Motivated Strategies for Learning Questionnaire and also collected demographic information for a propensity score matching process. Users’ frequency of accessing the intervention was categorized as High, Moderate, or Low/No usage. After matching users on characteristics associated with dashboard usage (gender, high school GPA, and the “Test Anxiety” and “Self Efficacy” factors) we found that both the “High” and “Moderate” users achieved significantly higher course grades than the “Low/No” users. The results suggest learners benefited from regularly accessing the feedback, but extreme amounts of usage were not necessary to achieve a positive effect. We discuss the implications for recommending how students use learning analytics interventions without excessively accessing feedback.

Objectives The Akaike Information Criterion (AIC) is a well-known tool for variable selection in multivariable modeling as well as a tool to help identify the optimal representation of explanatory variables. However, it has been discussed infrequently in the dental literature. The purpose of this paper is to demonstrate the use of AIC in determining the optimal representation of dietary variables in a longitudinal dental study. Methods The Iowa Fluoride Study enrolled children at birth and dental examinations were conducted at ages 5, 9, 13, and 17. Decayed or filled surfaces (DFS) trend clusters were created based on age 13 DFS counts and age 13-17 DFS increments. Dietary intake data (water, milk, 100 percent-juice, and sugar sweetened beverages) were collected semiannually using a food frequency questionnaire. Multinomial logistic regression models were fit to predict DFS cluster membership (n=344). Multiple approaches could be used to represent the dietary data including averaging across all collected surveys or over different shorter time periods to capture age-specific trends or using the individual time points of dietary data. Results AIC helped identify the optimal representation. Averaging data for all four dietary variables for the whole period from age 9.0 to 17.0 provided a better representation in the multivariable full model (AIC=745.0) compared to other methods assessed in full models (AICs=750.6 for age 9 and 9-13 increment dietary measurements and AIC=762.3 for age 9, 13, and 17 individual measurements). The results illustrate that AIC can help researchers identify the optimal way to summarize information for inclusion in a statistical model. Conclusions The method presented here can be used by researchers performing statistical modeling in dental research. This method provides an alternative approach for assessing the propriety of variable representation to significance-based procedures, which could potentially lead to improved research in the dental community.

Published Lyme meningitis treatment studies are limited by outcome measures that cannot capture day-to-day differences in clinical improvement. Our goal was to use expert consensus to develop a daily measurement instrument for assessing clinical improvement in children with Lyme meningitis. We assembled a panel of 24 nationally recognized Lyme disease experts to develop a pediatric daily symptom measurement instrument. Experts responded to four rounds of surveys, receiving feedback about the previous round prior to each subsequent round with anonymity for participants and responses. Using modified Delphi methods, we established a novel Lyme meningitis outcome instrument. The final Pediatric Lyme Meningitis Symptom Measurement instrument includes five items: headache (Likert scale), neck pain/stiffness (Likert scale), fever (yes/no), light sensitivity (yes/no) and vision problems (yes/no). We defined three consecutive days with a symptom score of zero as the minimum to define clinical improvement. Using expert consensus, we developed a novel Pediatric Lyme Meningitis Symptom Measurement instrument to measure treatment response daily for children with Lyme meningitis enrolled in clinical studies.

Glaucoma is the second leading cause of blindness in the USA. A visual field test (perimetry) is used to sample and quantitate visual field function in preselected regions in the eye. These regions can be considered a spatial field with replications across independently measured individuals. At return visits, a new set of visual field measurements is obtained producing a subject specific spatio-temporal dataset. We develop a Bayesian hierarchical modeling framework to analyze these spatio-temporal datasets both for individual level spread and as aggregate population level trends. Our model extends previous research utilizing a dimension reduction matrix and individual specific latent variables. Human characteristics are incorporated into the model to help explain glaucoma progression. One beneficial product of our model is smoothed estimates for individuals. We also specify how progression rates are computed for monitoring purposes so that clinicians can track changes and predict forward in time. Copyright © 2016 John Wiley & Sons, Ltd.

Our objective is to retrospectively describe longitudinal beverage intakes and anthropometric measures according to adolescent beverage patterns. Data were collected from Iowa Fluoride Study participants (n = 369) using beverage questionnaires at ages 2&ndash, 17 years. Weight and height were measured at ages 5, 9, 13 and 17 years. Cluster analyses were used to identify age 13- to 17-year beverage patterns. Treating age and beverage cluster as explanatory factors, sex-specific generalized linear mixed models were used to identify when differences in beverage intakes and anthropometric measures began. Predominant beverage intakes were higher in each of the corresponding clusters by 9&ndash, 12.5 years, females with high milk intakes during adolescence and males with high 100% juice or sugar-sweetened beverage intakes during adolescence reported higher intakes of that beverage beginning at 2&ndash, 4.7 years. Females and males in the 100% juice cluster had lower weights than other clusters beginning at 13 years, while females and males in the neutral cluster were shorter beginning at 13 years. Females in the water/sugar-free beverage cluster had higher body mass indices (BMIs) beginning at 9 years. Females and males in the 100% juice cluster had lower BMIs beginning at 5 and 9 years, respectively. Childhood beverage intakes and growth patterns differ according to adolescent beverage patterns.

Heart failure (HF) is a costly and growing health problem that is routinely complicated by chronic pain and depression. The purpose of this paper is to describe the characteristics of pain and pain management in depressed HF patients. In this descriptive cross-sectional study, we analyzed data from 62 participants with depression and class II-IV HF. Study variables of interest were collected from the Brief Pain Inventory, Beck Depression Inventory, and Rand-36. Almost all participants (98%) had some pain in the past month and most had pain in the last 24 hours (66%). The median pain score was 4 (0-10 scale) with the majority reporting moderate to severe pain. The median pain interference score was 4.42 (0-10 scale) with the majority reporting moderate to extreme interference. Medication to treat pain was used by all participants who reported pain, with only 5% also using nonpharmacologic treatment. The majority of participants reported moderate or severe pain while also having moderate to extreme pain interference. Nonpharmacologic pain treatments were severely underused. Women were more likely to have higher levels of pain intensity and more pain interference than men, suggesting that additional screening for the impact of pain is especially important in women. The wide variety of body areas affected, along with moderate to high intensity pain and considerable interference scores reported, indicate that pain was ineffectively treated. Nonpharmacologic treatments should be considered to decrease the impact of pain.

Haiti, a country marked by extreme poverty and poor health, is also an active site for thousands of non-governmental organizations. The community needs assessment is an important tool that allows aid organizations to understand better community perspectives regarding health. In this study, 84 community members were interviewed across three geographically proximate communities in the Arcahaie region of Haiti to identify similarities and differences in community needs. Overall, the most important public health-related problems included access to clean water, sanitation, health care, and education. In discussing these topics, similarities were observed in drinking water source and relative lack of water treatment. Significant differences were noted between the communities in health care source. There were no significant differences in school enrollment patterns across communities, but there were differences in gendered enrollment. This broad survey affirms the importance of understanding the needs of individual communities in order to implement effective public health interventions.

Introduction Increasing patients' physical activity levels holds many opportunities to facilitate health and well-being among those with heart failure (HF) by improving HF symptoms and decreasing depression and pain. Given low exercise participation rates, an essential first step to increase exercise rates is to evaluate how pain and depression may further influence engagement in exercise programs. Aims The aims of this study were to describe the level of physical activity and exercise that patients with HF with depression achieve and to investigate the relationships among pain, depression, total activity time, and sitting time. Methods In this correlational cross-sectional study, we analyzed data from 61 participants with depression and New York Heart Association class II to IV HF. Results and conclusions The total time spent being active was less than 1 hour per day. Depressed patients with HF have much lower physical activity levels than the general public. Decreasing sitting time and increasing light activity levels hold promise to improve pain and depression symptoms.

IMPORTANCE: Clinicians often risk stratify young febrile infants for invasive bacterial infections (IBIs), defined as bacteremia and/or bacterial meningitis, using complete blood cell count parameters. OBJECTIVE: To estimate the accuracy of individual complete blood cell count parameters to identify febrile infants with IBIs. DESIGN, SETTING, AND PARTICIPANTS: Planned secondary analysis of a prospective observational cohort study comprising 26 emergency departments in the Pediatric Emergency Care Applied Research Network from 2008 to 2013. We included febrile (≥38°C), previously healthy, full-term infants younger than 60 days for whom blood cultures were obtained. All infants had either cerebrospinal fluid cultures or 7-day follow-up. MAIN OUTCOMES AND MEASURES: We tested the accuracy of the white blood cell count, absolute neutrophil count, and platelet count at commonly used thresholds for IBIs. We determined optimal thresholds using receiver operating characteristic curves. RESULTS: Of 4313 enrolled infants, 1340 (31%; 95% CI, 30% to 32%) were aged 0 to 28 days, 2412 were boys (56%), and 2471 were white (57%). Ninety-seven (2.2%; 95% CI, 1.8% to 2.7%) had IBIs. Sensitivities were low for common complete blood cell count parameter thresholds: white blood cell count less than 5000/µL, 10% (95% CI, 4% to 16%) (to convert to 10(9) per liter, multiply by 0.001); white blood cell count ≥15 000/µL, 27% (95% CI, 18% to 36%); absolute neutrophil count ≥10 000/µL, 18% (95% CI, 10% to 25%) (to convert to × 10(9) per liter, multiply by 0.001); and platelets

Dosimetry for 10-MV x rays has been extended to radiation fields smaller than 4 X 4 cm which may be suitable for radiation therapy of small lesions, e.g., intracranial tumors, benign or malignant. Special consideration in this study was given to (i) the variation of dose with field size (collimator and phantom scatter), (ii) the central axis percentage depth doses, and (iii) the moving-beam therapy dose distribution. We conclude that simple dosimetric techniques can provide adequate physics background for stereotaxic radiosurgery with small radiation fields and high-energy x rays.

The death rate of brain abscesses in a recently reported series is high, ranging from 36% to 50% of all cases. This paper reports experiences with ten cases of intracranial abscesses secondary to ear and sinus infections. Six of these abscesses are secondary to otitic infections with three of them located in the cerebellum. Two of the cerebellar abscesses are surgically drained through the temporal bone by the otologic surgeon, with close neurosurgical cooperation. Computerized axial tomography has revolutionized the treatment of intracranial abscesses optimizing the timing for medical and surgical management.

Background It is uncertain whether switching to frequent nocturnal hemodialysis improves cognitive function in well-dialyzed patients and how this compares to patients who receive a kidney transplant. Methods We conducted a multicenter observational study with longitudinal follow-up of the effect on cognitive performance of switching dialysis treatment modality from conventional thrice-weekly hemodialysis to frequent nocturnal hemodialysis, a functioning renal transplant or remaining on thrice-weekly conventional hemodialysis. Neuropsychological tests of memory, attention, psychomotor processing speed, executive function and fluency as well as measures of solute clearance were performed at baseline and again after switching modality. The change in cognitive performance measured by neuropsychological tests assessing multiple cognitive domains at baseline, 4 and 12 months after switching dialysis modality were analyzed using a linear mixed model. Results Seventy-seven patients were enrolled; 21 of these 77 patients were recruited from the randomized Frequent Hemodialysis Network (FHN) Nocturnal Trial. Of these, 18 patients started frequent nocturnal hemodialysis, 28 patients received a kidney transplant and 31 patients remained on conventional thrice-weekly hemodialysis. Forty-eight patients (62 %) returned for the 12-month follow-up. Despite a significant improvement in solute clearance, 12 months treatment with frequent nocturnal hemodialysis was not associated with substantial improvement in cognitive performance. By contrast, renal transplantation, which led to near normalization of solute clearance was associated with clinically relevant and significant improvements in verbal learning and memory with a trend towards improvements in psychomotor processing speed. Cognitive performance in patients on conventional hemodialysis remained stable with the exception of an improvement in psychomotor processing speed and a decline in verbal fluency. Conclusions In patients on conventional thrice-weekly hemodialysis, receiving a functioning renal transplant was associated with improvement in auditory-verbal memory and psychomotor processing speed, which was not observed after 12 months of frequent nocturnal hemodialysis. Electronic supplementary material The online version of this article (doi:10.1186/s12882-016-0223-9) contains supplementary material, which is available to authorized users.