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Objective: Suicide rates and frequency of pediatric emergency department (ED) visits for suicidal thoughts and behaviors have increased among Black preadolescents in the United States in recent years. This study examined whether characteristics of ED visits and treatment management of preadolescents with suicidal thoughts and behaviors differed by race., Methods: An electronic medical record query identified patients ages 8-12 (N=504) who visited a pediatric ED with a psychiatric-related chief complaint in 2019. The authors examined suicidal thoughts and behaviors that were reported with the Ask Suicide-Screening Questions tool, ED clinical impression, and ED disposition overall and by race., Results: Compared with other racial groups, Black preadolescents were less likely to report suicidal thoughts, despite equivalent lifetime histories of suicide attempts, and were more likely to be brought to the ED by police and discharged (instead of being admitted to inpatient psychiatric care)., Conclusions: Research to better understand racial disparities in suicide risk among preadolescents can inform prevention efforts.

In psychiatric and social epidemiology studies, it is common to measure multiple different outcomes using a comprehensive battery of tests thought to be related to an underlying construct of interest. In the research that motivates our work, researchers wanted to assess the impact of in utero alcohol exposure on child cognition and neuropsychological development, which are evaluated using a range of different psychometric tests. Statistical analysis of the resulting multiple outcomes data can be challenging, because the outcomes measured on the same individual are not independent. Moreover, it is unclear, a priori, which outcomes are impacted by the exposure under study. While researchers will typically have some hypotheses about which outcomes are important, a framework is needed to help identify outcomes that are sensitive to the exposure and to quantify the associated treatment or exposure effects of interest. We propose such a framework using a modification of stochastic search variable selection, a popular Bayesian variable selection model and use it to quantify an overall effect of the exposure on the affected outcomes. The performance of the method is investigated empirically and an illustration is given through application using data from our motivating study.

Background: In LMICs, including Indonesia, there is a rising burden of non-communicable diseases (NCDs) with a prevailing burden of infectious diseases, including among pregnant women. The Indonesian health system faces significant challenges to provide effective care for infectious diseases, and even more so, NCDs. This is concerning due to the greater vulnerability of pregnant women to complications caused by concomitant illnesses (NCDs and infectious diseases), and the need for complex, integrated healthcare between maternal care and other health services., Methods: The objective of this study was to understand supporting factors and challenges of the health system to providing care for concomitant illnesses in pregnancy and how it may be improved. Semi-structured interviews were conducted with sixteen key stakeholders, including health providers and health service managers, involved in maternal healthcare for concomitant illnesses at a District level in Indonesia. The study was conducted in Kutai Kartanegara District of East Kalimantan. Analysis was conducted using framework analysis to identify themes from transcripts., Results: Supporting factors of the health system to provide care for concomitant illness in pregnancy included collaboration between health providers and health services, availability of screening and diagnostic tools, and access to universal healthcare coverage and financial subsidies. Common challenges included knowledge and awareness of concomitant illnesses among health providers, competency to diagnose and/or manage concomitant illnesses, and inappropriate referrals. Suggested improvements identified to address these gaps included increasing education and refresher training for healthcare providers and strengthening referrals between primary and hospital care., Conclusions: The findings identified gaps in the health system to provide care for concomitant illnesses in pregnancy in Indonesia that need to be strengthened. More evidence-based research is needed to guide the implementation of policy and practice interventions for the health system to deal with a broader range of concomitant illnesses in pregnancy, particularly NCDs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Ryan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Evidence from animal models and epidemiological studies has linked prenatal alcohol exposure (PAE) to a broad range of long-term cognitive and behavioural deficits. However, there is a paucity of evidence regarding the nature and levels of PAE associated with increased risk of clinically significant cognitive deficits. To derive robust and efficient estimates of the effects of PAE on cognitive function, we have developed a hierarchical meta-analysis approach to synthesize information regarding the effects of PAE on cognition, integrating data on multiple outcomes from six U.S. Iongitudinal cohort studies. A key assumption of standard methods of meta-analysis, effect sizes are independent, is violated when multiple intercorrelated outcomes are synthesized across studies. Our approach involves estimating the dose-response coefficients for each outcome and then pooling these correlated dose-response coefficients to obtain an estimated "global" effect of exposure on cognition. In the first stage, we use individual participant data to derive estimates of the effects of PAE by fitting regression models that adjust for potential confounding variables using propensity scores. The correlation matrix characterizing the dependence between the outcome-specific dose-response coefficients estimated within each cohort is then run, while accommodating incomplete information on some outcome. We also compare inferences based on the proposed approach to inferences based on a full multivariate analysis.

Objective: Gaps remain in our understanding on how COVID19 affects trends in pediatric trauma, the leading cause of mortality and morbidity during childhood and adolescence., Methods: We compared high acuity trauma visits (requiring admission, surgery, or fatality) presenting between March through February 2021 to corresponding months in 2017-2019. We evaluated the differences in mechanisms of injury, age, and Area Deprivation Index (ADI), a measure of socioeconomic disadvantage, during this time period. Data were analyzed using longitudinal time series analyses and t-tests., Results: Of 687 traumas presenting from March 2020 through February 2021, 322 were high acuity traumas. High acuity traumas declined significantly to a nadir of 16 in April 2020. High acuity traumas increased and surpassed previous years to a peak of 40 visits in August 2020 and from October through December 2020. There were more visits for high acuity assaults and confirmed or suspected physical child abuse but fewer for falls, drownings, and motor vehicle accidents from March to August 2020 and from October through December 2020 compared to prior years. High acuity assaults and physical child abuse cases on average were from the most disadvantaged areas, and physical child abuse patients were younger during the peak of the Pandemic compared to Pre-Pandemic months., Conclusion: This analysis provides insight into how the COVID19 pandemic has affected high acuity trauma in an inner-city pediatric population. Findings may be used to guide public health measures on safety and injury prevention as the pandemic continues., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Head injuries are a leading cause of death and disability in children, accounting for numerous emergency department (ED) visits. It is unclear how the COVID-19 pandemic has influenced healthcare utilization for pediatric head injuries. We hypothesize that the proportion of ED visits attributable to head injury and severity will increase during the COVID-19 era. Retrospective study using electronic health record data to compare proportion and severity of head injury for children 0-21 years of age from three urban mid-Atlantic EDs in the pre-COVID-19 era (March-June 2019) and COVID-19 era (March-June 2020). Controlling for confounders, logistic regression analyses assessed ORs of head injury outcomes. The χ 2 analyses identified differences in patient characteristics. The proportion of head injury visits within the ED population significantly increased during the COVID-19 era (adjusted OR (aOR)=1.2, 95% CI 1.1 to 1.4). Proportion of visits requiring hospitalization for head injury increased by more than twofold in the COVID-19 era (aOR=2.3, 95% CI 1.3 to 4.3). Use of head CT imaging did not significantly change in the COVID-19 era (aOR=1.0, 95% CI 0.7 to 1.6). The proportion of ED visits and hospitalizations for head injury increased during the COVID-19 era. This could be due to changes in the level of supervision and risk exposures in the home that occurred during the pandemic, as well as differences in postinjury care, level of awareness regarding injury severity, and threshold for seeking care, all of which may have influenced pediatric healthcare utilization for head injuries., Competing Interests: Competing interests: LMR is a Journal of Investigative Medicine editorial board member., (© American Federation for Medical Research 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: Paediatric emergency departments (ED) nationwide experience a shared burden of boarding mental health patients. Whilst boarding, some patients have a change in disposition from hospitalization to discharge home. This phenomenon raises concern because EDs often have scarce resources for mental health patients. We sought to understand which patient and clinical factors are associated with a change in disposition outcome., Methods: A nested age-sex-race frequency-matched case-control study was conducted including paediatric patients who presented to an urban PED for mental healthcare over a 36-month period. Control patients included patients admitted to an inpatient psychiatric facility, whilst case patients were those discharged home. Descriptive statistics and multivariable logistic regression analyses were performed to compare groups., Results: Case patients were more likely to receive intramuscular Haloperidol (OR 2.2 [CI 1.1-4.4]) for agitation and a psychiatric consult (OR 2.3 [1.4-3.9]) whilst boarding. Case patients were also more likely to present with behavioural concerns (OR 1.8 [CI 1.1-3.1]) and have additional complexities such as medical comorbidities (OR 1.8 [CI 1.1-2.9]) or suicidal ideation/attempt (OR 2.6 [CI 1.1-6.1]). Amongst the most common themes for disposition change was improved patient status (58.8%)., Conclusion: These findings suggest that boarding mental health patients have different disposition outcomes and thus may benefit from patient-specific treatment interventions. Given that patients' statuses may change during the boarding period prompting discharge to home, more focus should be directed to developing brief evidence-based practises that may be implemented in the ED and effectively bridge the gap to outpatient mental health services., (© 2021 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

This retrospective cohort study at an urban academic pediatric emergency department (ED) in the United States identified all visits for youth 10-15 years of age for injury due to intentional interpersonal violence between January 2019 and December 2020. Demographic and clinical data were abstracted, including circumstances of the event. Data analysis included a comparison of pre-pandemic visits to pandemic visits after a statewide stay-at-home order was issued (March 30, 2020). Of 2780 10-15 year old youth evaluated for any injury, 819 (29.5%) had intentional/violence-related injuries. Most patients were male (53.1%), Black/African-American (84.1%), and were enrolled in a public insurance plan (75.0%). Although peer-violence related injuries comprised a substantial proportion (19.2%), the majority resulted from family violence (54.7%), which may include child maltreatment or physical fighting. Most injuries occurred at home (53.9%). Alcohol, drugs and weapons were significantly more likely to be involved in violent events during the pandemic in comparison to pre-pandemic (12.5 vs 5.0%, 11.4% vs 3.0%, 30.4% vs 8.5%; p < 0.001). Our findings support the need for ED-based efforts to screen and intervene for family and peer violence and other contributory factors (including personal, family and peer alcohol, drug and weapons access) when youth present with intentional injuries, which can be critical to preventing future violence.

Objective: To describe demographic, injury, and clinical characteristics of pediatric patients treated in the ED for mild traumatic brain injury (mTBI), and to evaluate characteristics associated with mTBI-related return emergency department (ED) visit within 1 month of initial presentation., Methods: Retrospective cohort study from April 1, 2012, to September 30, 2017, of children 19 years or younger presenting to any Maryland ED for mTBI identified in the Maryland Health Services Cost Review Commission database using ICD-9/10 codes. Demographic, injury, and clinical characteristics of individuals were collected. The primary outcome was mTBI-related return ED visit within 4 weeks. Multiple logistic regression tested the associated of individual demographic, injury, and clinical characteristics with mTBI-related return ED visit., Results: There were 25,582 individuals who had an ED visit for mTBI, of which 717 (2.8%) returned to the ED within 4 weeks and 468 (1.8%) within 1 week with a mTBI-related diagnosis. In multivariable logistic regression analyses, public insurance (adjusted odds ratio [aOR], 1.44; 95% confidence interval [CI], 1.21-1.72) and female sex (aOR, 1.34; 95% CI, 1.15-1.56) were associated with increased odds of return to the ED within 4 weeks. Age younger than 2 years (aOR, 0.39; 95% CI, 0.21-0.72) was associated with decreased odds of return visit. There was a trend toward decreased odds of return patients receiving computed tomography head imaging (aOR, 0.86; 95% CI, 0.74-1.01)., Conclusions: Although return to the ED for mTBI-related complaints is uncommon, girls, older children, and publicly insured individuals may be at increased risk. Future targeted study may identify areas to improve access to appropriate longitudinal care and justify ED programs to better coordinate follow-up for mTBI., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Cognitive and behavioral sequelae of prenatal alcohol exposure (PAE) continue to be prevalent in the United States and worldwide. Because these sequelae are also common in other neurodevelopmental disorders, researchers have attempted to identify a distinct neurobehavioral profile to facilitate the differential diagnosis of fetal alcohol spectrum disorders (FASD). We used an innovative, individual participant meta-analytic technique to combine data from six large U.S. longitudinal cohorts to provide a more comprehensive and reliable characterization of the neurobehavioral deficits seen in FASD than can be obtained from smaller samples., Methods: Meta-analyses were performed on data from 2236 participants to examine effects of PAE (measured as oz absolute alcohol/day (AA/day)) on IQ, four domains of cognition function (learning and memory, executive function, reading achievement, and math achievement), sustained attention, and behavior problems, after adjusting for potential confounders using propensity scores., Results: The effect sizes for IQ and the four domains of cognitive function were strikingly similar to one another and did not differ at school age, adolescence, or young adulthood. Effect sizes were smaller in the more middle-class Seattle cohort and larger in the three cohorts that obtained more detailed and comprehensive assessments of AA/day. PAE effect sizes were somewhat weaker for parent- and teacher-reported behavior problems and not significant for sustained attention. In a meta-analysis of five aspects of executive function, the strongest effect was on set-shifting., Conclusions: The similarity in the effect sizes for the four domains of cognitive function suggests that PAE affects an underlying component or components of cognition involving learning and memory and executive function that are reflected in IQ and academic achievement scores. The weaker effects in the more middle-class cohort may reflect a more cognitively stimulating environment, a different maternal drinking pattern (lower alcohol dose/occasion), and/or better maternal prenatal nutrition. These findings identify two domains of cognition-learning/memory and set-shifting-that are particularly affected by PAE, and one, sustained attention, which is apparently spared., (© 2021 by the Research Society on Alcoholism.)

Propensity score methodology has become increasingly popular in recent years as a tool for estimating causal effects in observational studies. Much of the related research has been directed at settings with binary or discrete exposure variables with more recent work involving continuous exposure variables. In environmental epidemiology, a substantial proportion of individuals is often completely unexposed while others may experience heavy exposure leading to an exposure distribution with a point mass at zero and a heavy right tail. We suggest a new approach to handle this type of exposure data by constructing a propensity score based on a two-part model and show how this model can be used to more reliably adjust for covariates of a semi-continuous exposure variable. We also consider the case when a misspecified propensity score is used in a regression adjustment and derive an explicit form of the bias. We show that the potential bias gets smaller as the estimated propensity score gets closer to the true expectation of the exposure variable given a set of observed covariates. While this result pertains to a more general setting, we use it to evaluate the potential bias in settings in which the true exposure has a semi-continuous structure. We also evaluate and compare the performance of our proposed method through simulation studies relative to a simpler linear regression-based propensity score for a continuous exposure variable as well as through direct covariate adjustment. Overall, we find that using a propensity score constructed via a two-part model significantly improves the regression estimate when the exposure variable is semi-continuous in nature. Specifically when the proportion of non-exposed subjects is high and the effects of covariates on exposure and outcome are strong, the proposed two-part propensity score method outperforms the more standard competing methods. We illustrate our method using data from the Detroit Longitudinal Cohort Study in which the exposure variable reflects gestational alcohol exposure featuring zero values and a long tail.

The association of household composition with violence-related injury risk has not been explored in the at-risk urban adolescent population. We hypothesize that, similar to the unintentional risk association, higher adult:child ratio, lower household size, and the presence of a grandparent are protective and thus associated with lower risk for repeat fight injury in this population. This is a cross-sectional study of 10- to 15-year-old adolescents who were evaluated in two urban, pediatric emergency departments (EDs; Baltimore, MD, Philadelphia, PA) for a peer fight-related injury between June 2014 and June 2016. Logistic regression was used to test for associations between each household composition measure of interest and youth self-report of a medically attended fight-related injury within the prior 12 months. Of 187 eligible youth, 62 (33%) reported at least one such repeat fight-related injury. With control for potential confounders, youth with past fight injuries did not differ in adult:child ratio (adjusted odds ratio [adj OR] = 1.3, 95% confidence interval [CI]: [0.9, 1.9] ) or household size (adj OR = 0.9, 95% CI: [0.8, 1.1]) but were more likely to have a grandparent residing in the household (adj OR = 3.3, 95% CI: [1.4, 7.9]). Our data demonstrate a positive association between presence of a grandparent in the household and risk for repeat fight injury in urban adolescents without a corresponding association with adult:child ratio or total household size. Further study should explore differences among the households of urban adolescents with and without grandparent presence to further understand this association and define the mechanisms that may contribute to these findings.

Background and Objectives: The Covid-19 pandemic has forced mass closures of childcare facilities and schools. While these measures are necessary to slow virus transmission, little is known regarding the secondary health consequences of social distancing. The purpose of this study is to assess the proportion of injuries secondary to physical child abuse (PCA) at a level I pediatric trauma center during the Covid-19 pandemic., Methods: A retrospective review of patients at our center was conducted to identify injuries caused by PCA in the month following the statewide closure of childcare facilities in Maryland. The proportion of PCA patients treated during the Covid-19 era were compared to the corresponding period in the preceding two years by Fisher's exact test. Demographics, injury profiles, and outcomes were described for each period., Results: Eight patients with PCA injuries were treated during the Covid-19 period (13 % of total trauma patients), compared to four in 2019 (4 %, p < 0.05) and three in 2018 (3 %, p < 0.05). The median age of patients in the Covid-19 period was 11.5 months (IQR 6.8-24.5). Most patients were black (75 %) with public health insurance (75 %). All injuries were caused by blunt trauma, resulting in scalp/face contusions (63 %), skull fractures (50 %), intracranial hemorrhage (38 %), and long bone fractures (25 %)., Conclusions: There was an increase in the proportion of traumatic injuries caused by physical child abuse at our center during the Covid-19 pandemic. Strategies to mitigate this secondary effect of social distancing should be thoughtfully implemented., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To compare radiation doses used for pediatric computed tomography (CT) scans at community-based referring facilities (RF) to those at a designated pediatric trauma center (PTC) to assess the consistency of radiation exposure., Methods: In this retrospective study, patients 0 to 18 years of age with CT imaging performed either at a RF or at a PTC from January 1, 2015, to January 5, 2016, were identified. Data about patients, CT radiation dose, and characteristics of the RFs were compared., Results: We identified 502 patients (156 RF, 346 PTC) with 281 head CTs (79 RF, 202 PTC) and 86 abdominal/pelvis CTs (28 RF, 58 PTC). The radiation dose (measured in mean dose-length product [DLP] ± 1 standard deviation) was significantly higher for RF scans compared with PTC scans (head, RF DLP = 545 ± 334 vs PTC DLP = 438 ± 186 (P < 0.001); abdomen/pelvis, RF DLP = 279 ± 160 vs PTC DLP = 181 ± 201 [P = 0.027]). There was a nonsignificant trend toward lower head CT radiation dosages at RFs with a dedicated pediatric emergency department compared with RFs without a pediatric emergency department., Conclusions: Our data suggest that CT scans performed at RFs expose pediatric patients to significantly higher doses of radiation when compared with a PTC. These data support further study to identify factors associated with increased radiation and educational outreach to RFs., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: 'Indirect' causes of maternal death including concomitant illnesses such as infectious and non-communicable diseases (NCDs), accounted for 23% of maternal deaths in Indonesia in 2010. Reproductive-age women in Indonesia face a "double burden" of disease with increasing rates of NCDs and persisting rates of infectious disease. However, there is a lack of data on the burden of these diseases in pregnancy. The aim of this study was to estimate incidence of concomitant illnesses among pregnant women in Indonesia from 1990-2030., Methods: Publicly available data was accessed including incidence of concomitant illnesses in Indonesian reproductive-age women, population data and crude birth rate data from 1990-2019, and formed basis for projections to 2030. A dataset of estimates for all variables was generated for each year and sampled from a binomial distribution. Using these estimates, pregnancy estimates and incidence in pregnant women were calculated. A cubic splines model was fitted to generate estimates of incidence of concomitant illnesses in pregnancy., Findings: Past trends to 2019 show a decline in incident cases of infectious diseases except for HIV/AIDs, and an increase in most NCDs. In 2019, the most common disease was sexually transmitted infections. From 2020-2030, incidences of diabetes and lower respiratory infections are estimated to continue to increase., Interpretation: With an increasing incidence of NCDs and high-incidence of infectious diseases in pregnancy, Indonesian policymakers and stakeholders should consider what evidence-based strategies and interventions are best to reduce potential impacts of concomitant illnesses on pregnancy outcomes., Funding: Australian Government Research Training Program Scholarship., Competing Interests: We declare no competing interests., (© 2021 The Author(s). Published by Elsevier Ltd.)

Invasive species have emerged as a significant problem in the age of anthropogenic change. Behavior can be key to invasive species success and is strongly affected by temperature. Therefore, knowledge of the temperature dependence of behavior is likely critical to understand invasive species dynamics and their interactions with native species. In this study, we tested for differences in thermal preference plasticity and temperature-dependent activity levels in a pair of congeneric lizards found in the United States: the invasive Anolis sagrei and the native A. carolinensis. We predicted that A. sagrei would demonstrate greater thermal preference plasticity and would utilize a higher and/or wider range of activity temperatures than A. carolinensis. Both would point to plasticity allowing A. sagrei to behaviorally exploiting thermal conditions that A. carolinensis cannot. We found that both species exhibited plasticity in thermal preference, but in opposite directions: preferred temperatures of A. carolinensis increased with acclimation temperature, while those of A. sagrei decreased. As a result, which species had a higher thermal preference changed with acclimation conditions. We saw no difference in overall field activity rates between the species, but that A. sagrei did tend to be active over a broader range of body temperatures. In sum, we found little evidence that differences in thermal preference plasticity between the species allow A. sagrei to remain active at a higher or broader temperature range than A. carolinensis. Nonetheless, the thermal preference data suggest complementary thermal preferences between the species that could promote microclimatic partitioning, though more work is required to test this idea., (© 2020 Wiley Periodicals LLC.)

Bicycle-related falls are a significant cause of mortality and morbidity. Use of bicycle helmets substantially reduces risk of severe traumatic brain injury but compliance with this safety practice is particularly low in urban children. Given the lack of educational interventions for urban youth, our research team created a youth-informed, culturally relevant educational video on bike helmet safety, which was informed by focus groups with Baltimore City youth. This video, You Make the Call, linked the concept of use of cases to protect phones to use of helmets to protect heads and can be viewed at http://bit.ly/2Kr7UCN. The impact of the video as part of an intervention (coupled with a free helmet, fit instructions, and a parent guidance document) was tested with 20 parent-child dyads. The majority (80%) of youth (mean age 9.9 ± 1.8 years) reported not owning or wearing a helmet. At 1-month follow-up (n = 12, 60% response rate), helmet use was higher in the five youth reporting bike-riding after the intervention; 100% "always" used helmets compared to 0% preintervention. There were increases in youth reporting that parents required helmet use (35% pre vs. 67% post) and that is was possible to fall when bike-riding (60% pre vs. 92% post). These pilot results support the use of this video and educational intervention along with further evaluation in a larger sample size. This youth-informed and culturally tailored approach could be explored as a strategy to address other pediatric injury topics.

Introduction: Assessments of executive functions (EFs) with varying levels of perceptual information or action fidelity are common talent-diagnostic tools in soccer, yet their validity still has to be established. Therefore, a longitudinal development of EFs in high-level players to understand their relationship with increased exposure to training is required., Methods: A total of 304 high-performing male youth soccer players (10-21 years old) in Germany were assessed across three seasons on various sport-specific and non-sport-specific cognitive functioning assessments., Results: The posterior means (90% highest posterior density) of random slopes indicated that both abilities predominantly developed between 10 and 15 years of age. A plateau was apparent for domain-specific abilities during adolescence, whereas domain-generic abilities improved into young adulthood., Conclusion: The developmental trajectories of soccer players' EFs follow the general populations' despite long-term exposure to soccer-specific training and game play. This brings into question the relationship between high-level experience and EFs and renders including EFs in talent identification questionable.

Background: Postresuscitation debriefing (PRD) is recommended by the American Heart Association guidelines but is infrequently performed. Prior studies have identified barriers for pediatric emergency medicine (PEM) fellows including lack of a standardized curriculum., Objective: Our objective was to create and assess the feasibility of a time-limited, structured PRD framework entitled REFLECT: Review the event, Encourage team participation, Focused feedback, Listen to each other, Emphasize key points, Communicate clearly, and Transform the future., Methods: Each PEM fellow (n = 9) at a single center was a team leader of a pre-intervention and post-intervention videotaped, simulated resuscitation followed by a facilitated team PRD. Our intervention was a 2-hour interactive, educational workshop on debriefing and the use of the REFLECT debriefing aid. Videos of the pre-intervention and post-intervention debriefings were blindly analyzed by video reviewers to assess for the presence of debriefing characteristics contained in the REFLECT debriefing aid. PEM fellow and team member assessments of the debriefings were completed after each pre-intervention and post-intervention simulation, and written evaluations by PEM fellows and team members were analyzed., Results: All 9 PEM fellows completed the study. There was an improvement in the pre-intervention and post-intervention assessment of the REFLECT debriefing characteristics as determined by fellow perception (63% to 83%, P < 0.01) and team member perception (63% to 82%, P < 0.001). All debriefings lasted less than 5 minutes. There was no statistical difference between pre-intervention and post-intervention debriefing time (P = 1.00)., Conclusions: REFLECT is a feasible debriefing aid designed to incorporate evidence-based characteristics into a PRD.

Background: Injured children who arrive by self-transport to the emergency department (ED) may receive delayed or inadequate care. We studied differences in demographics, clinical characteristics, and trauma activation status for admitted pediatric trauma patients based on arrival by self-transport or Emergency Medical Services (EMS)., Materials and Methods: We performed a retrospective cohort study at two level I pediatric trauma centers., Inclusion Criteria: <15 y old with blunt or penetrating injury. We used univariate and multivariate logistic regression analyses to determine associations between trauma activation, ED length of stay (LOS), and hospital LOS with demographic and clinical characteristics., Results: We identified 1161 patients: 40.1% arrived by self-transport and 59.9% by EMS. Self-transport patients were less likely to have an abnormal Glasgow Coma Scale score < 15 (2.1% versus 22.0%, P < 0.001) and Injury Severity Score > 15 (2.4% versus 11.7%, P < 0.001). Trauma activation was initiated in 52.5% of patients, occurring less often in self-transport than EMS patients (2.4% versus 86.2%, P < 0.001). Trauma activation rate was negatively associated with arrival by self-transport (odds ratio [OR] 0.001, 95% CI 0.00-0.003), positively associated with Glasgow Coma Scale <15 (OR 25.9, 95% CI 6.6-101.2) and site (OR 15.4, 95% CI 6.3-37.5) but not with Injury Severity Score >15 (OR 2.8, 95% CI 0.8-9.2). Self-transport arrival was associated with longer ED LOS (estimated regression slope 0.47, 95% CI 0.13-0.82)., Conclusions: Almost half of admitted pediatric trauma patients arrived by self-transport; however, trauma team activation rarely occurs for these patients. Trauma team activation may be underutilized in self-transport patients with injuries resulting in hospital admission., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Bicycle-related falls are a significant cause of mortality and morbidity. Use of bicycle helmets substantially reduces risk of severe traumatic brain injury but compliance with this safety practice is particularly low in urban children. We recruited eleven 8- to 15-year-old youth to participate in focus groups to inform the creation of a video promoting helmet use. Key emerging themes included that youth were responsible for keeping themselves safe and that most youth had cell phones with cases to protect them. A video was created that linked the concept of use of cases to protect phones to use of helmets to protect heads. Soliciting information from urban youth was helpful for developing this educational video.

This study sought to determine the proportion of children with long bone fractures who undergo duplicate radiographic imaging after transfer to a pediatric trauma center (PTC) for further management. The secondary objective was to explore provider rationale and diagnostic yield of repeat X-rays. This was a single-site, retrospective cohort study conducted at a PTC. All patients, aged 0-21 years, who were transferred to the PTC for management of a long bone fracture were included. Electronic medical records were reviewed to determine the proportion of children who had repeat radiographic imaging and the provider rationale for obtaining this. T-test and Χ 2 analyses were used to compare patients who had repeat X-rays with those who did not. During the study period, 309 patients (63% male, mean age 7.2±4.3 years) were transferred from 30 referring hospitals. Of these, 43% (n=133) underwent repeat radiographs. Patient age (p=0.9), gender (p=0.7), fracture location (p=0.19), and type of referring emergency department (pediatric vs general, p=0.3) were not significantly associated with repeat imaging. Rationale for repeat imaging could be ascertained in 31% of cases (n=41); the most common reasons were request by orthopedist (17%, n=23) and suboptimal original imaging (10%, n=13). Repeat imaging at the PTC did not reveal new or additional diagnoses in any case. Nearly half of the children in our study population undergo repeat and likely unnecessary imaging. Strategies to reduce repeat radiographs should be developed, as redundant imaging exposes patients to additional radiation and increases medical expense., Competing Interests: Competing interests: None declared., (© American Federation for Medical Research 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Calcium pyrophosphate deposition disease (CPDD) is arthritis caused by calcium pyrophosphate (CPP) crystal deposition in joints. It is commonly associated with aging as well as a handful of metabolic syndromes. Recent epidemiologic studies suggest a positive association of CPDD and rheumatoid arthritis (RA). Yet how these diseases are related remains unclear. We set out to describe 21 well-characterized patients with both diagnoses., Methods: Medical records of patients with both RA and CPDD identified at a single academic practice site were reviewed for age, gender, age of CPDD and RA onset, disease duration, joint involvement, and lab values including rheumatoid factor (RF), cyclic citrullinated peptide antibody (CCP), iron studies, and parathyroid hormone and calcium levels., Results: The mean age of CPDD onset was 69.5 ± 11.4 years, with a mean RA age onset of 53.9 ± 16 years, demonstrating a mean lag of 13.4 ± 10.9 years between diagnoses. The majority of RA patients were diagnosed with CPDD based on the presence of radiographic chondrocalcinosis (15/21). The most commonly involved joint was the knee, followed by the wrist, hip, and shoulder., Conclusions: These data show that the diagnosis of RA often precedes the diagnosis of CPDD. This asynchronous presentation taken together with the classic age of onset for CPDD and typical pattern of joint involvement supports the hypothesis that CPDD develops in RA patients through similar processes as those that cause the idiopathic forms of this disease., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Hypophosphatasia (HPP) is the inborn-error-of-metabolism due to loss-of-function mutation(s) of the ALPL (TNSALP) gene that encodes the tissue non-specific isoenzyme of alkaline phosphatase (TNSALP). TNSALP represents a family of cell-surface phosphohydrolases differing by post-translational modification that is expressed especially in the skeleton, liver, kidney, and developing teeth. Thus, the natural substrates of TNSALP accumulate extracellularly in HPP including inorganic pyrophosphate (PPi), a potent inhibitor of mineralization, and pyridoxal 5'-phosphate (PLP), the principal circulating form of vitamin B 6 . The superabundance of extracellular PPi regularly causes tooth loss, and when sufficiently great can lead to rickets or osteomalacia. Sometimes diminished hydrolysis of PLP engenders vitamin B 6 -dependent seizures in profoundly affected babies. Autosomal dominant and autosomal recessive inheritance from among >340 ALPL mutations identified to date, typically missense and located throughout the gene, largely explains the remarkably wide-ranging severity of HPP, greatest of all skeletal diseases. In 2015, our demographic, clinical, and DXA findings acquired over 25 years from 173 children and adolescents with HPP validated and expanded the clinical nosology for pediatric patients to include according to increasing severity "odonto" HPP, "mild childhood" HPP, "severe childhood" HPP, "infantile" HPP, and "perinatal" HPP. Herein, we assessed this expanded nosology using biochemical hallmarks of HPP. We evaluated exclusively data from the 165 preteenage HPP patients in this cohort to exclude potential effects from physiological changes in TNSALP levels across puberty. All patients had subnormal serum total and bone-specific ALP and elevated plasma PLP, and nearly all had excessive urinary PPi excretion. Only the PLP levels were unchanged across puberty. Mean levels of all four biomarkers correlated with HPP severity ranked according to the HPP nosology, but the data overlapped among all four patient groups. Hence, these four biochemical hallmarks represent both a sensitive and reliable tool for diagnosing children with HPP. Furthermore, the hallmarks validate our expanded clinical nosology for pediatric HPP that, with limitations, is an improved framework for conceptualizing and working with this disorder's remarkably broad-ranging severity., (Copyright © 2018 Elsevier Inc. All rights reserved.)

In many settings, an analysis goal is the identification of a factor, or set of factors associated with an event or outcome. Often, these associations are then used for inference and prediction. Unfortunately, in the big data era, the model building and exploration phases of analysis can be time-consuming, especially if constrained by computing power (ie, a typical corporate workstation). To speed up this model development, we propose a novel subsampling scheme to enable rapid model exploration of clustered binary data using flexible yet complex model set-ups (GLMMs with additive smoothing splines). By reframing the binary response prospective cohort study into a case-control-type design, and using our knowledge of sampling fractions, we show one can approximate the model estimates as would be calculated from a full cohort analysis. This idea is extended to derive cluster-specific sampling fractions and thereby incorporate cluster variation into an analysis. Importantly, we demonstrate that previously computationally prohibitive analyses can be conducted in a timely manner on a typical workstation. The approach is applied to analysing risk factors associated with adverse reactions relating to blood donation., (Copyright © 2017 John Wiley & Sons, Ltd.)

Cell wall-modifying enzymes have been previously investigated in charophyte green algae (CGA) in cultures of uniform age, giving limited insight into their roles. Therefore, we investigated the in situ localisation and specificity of enzymes acting on hemicelluloses in CGA genera of different morphologies and developmental stages. In vivo transglycosylation between xyloglucan and an endogenous donor in filamentous Klebsormidium and Zygnema was observed in longitudinal cell walls of young (1 month) but not old cells (1 year), suggesting that it has a role in cell growth. By contrast, in parenchymatous Chara , transglycanase action occurred in all cell planes. In Klebsormidium and Zygnema , the location of enzyme action mainly occurred in regions where xyloglucans and mannans, and to a lesser extent mixed-linkage β-glucan (MLG), were present, indicating predominantly xyloglucan:xyloglucan endotransglucosylase (XET) activity. Novel transglycosylation activities between xyloglucan and xylan, and xyloglucan and galactomannan were identified in vitro in both genera. Our results show that several cell wall-modifying enzymes are present in CGA, and that differences in morphology and cell age are related to enzyme localisation and specificity. This indicates an evolutionary significance of cell wall modifications, as similar changes are known in their immediate descendants, the land plants. This article has an associated First Person interview with the first author of the paper., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

Endocrine disrupting compounds (EDCs) are now widely established to be present in the environment at concentrations capable of affecting wild organisms. Although many studies have been conducted in fish, less is known about effects in invertebrates such as decapod crustaceans. Decapods are exposed to low concentrations of EDCs that may cause infertility, decreased growth, and developmental abnormalities. The objective herein was to evaluate effects of fipronil and its photodegradation product fipronil desulfinyl. Fipronil desulfinyl was detected in the eggs of the decapod Callinectes sapidus sampled off the coast of South Carolina. As such, to examine specific effects on C. sapidus exposed in early life, we exposed laboratory-reared juveniles to fipronil and fipronil desulfinyl for 96h at three nominal concentrations (0.01, 0.1, 0.5μg/l) and two different salinities (10, 30ppt). The size of individual crabs (weight, carapace width) and the expression of several genes critical to growth and reproduction were evaluated. Exposure to fipronil and fipronil desulfinyl resulted in significant size increases in all treatments compared to controls. Levels of expression for vitellogenin (Vtg), an egg yolk precursor, and the ecdysone receptor (EcR), which binds to ecdysteroids that control molting, were inversely correlated with increasing fipronil and fipronil desulfinyl concentrations. Effects on overall growth and on the expression of EcR and Vtg differ depending on the exposure salinity. The solubility of fipronil is demonstrated to decrease considerably at higher salinities. This suggests that fipronil and its photodegradation products may be more bioavailable to benthic organisms as salinity increases, as more chemical would partition to tissues. Our findings suggest that endocrine disruption is occurring through alterations to gene expression in C. sapidus populations exposed to environmental levels of fipronil, and that effects may be dependent upon the salinity at which exposure occurs., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The field of spatio-temporal modelling has witnessed a recent surge as a result of developments in computational power and increased data collection. These developments allow analysts to model the evolution of health outcomes in both space and time simultaneously. This paper models the trends in ischaemic heart disease (IHD) in New South Wales, Australia over an eight-year period between 2006 and 2013. A number of spatio-temporal models are considered, and we propose a novel method for determining the goodness-of-fit for these models by outlining a spatio-temporal extension of the Moran's I statistic. We identify an overall decrease in the rates of IHD, but note that the extent of this health improvement varies across the state. In particular, we identified a number of remote areas in the north and west of the state where the risk stayed constant or even increased slightly.

Most of the few published models used to obtain small-area estimates of relative survival are based on a generalized linear model with piecewise constant hazards under a Bayesian formulation. Limitations of these models include the need to artificially split the time scale, restricted ability to include continuous covariates, and limited predictive capacity. Here, an alternative Bayesian approach is proposed: a spatial flexible parametric relative survival model. This overcomes previous limitations by combining the benefits of flexible parametric models: the smooth, well-fitting baseline hazard functions and predictive ability, with the Bayesian benefits of robust and reliable small-area estimates. Both spatially structured and unstructured frailty components are included. Spatial smoothing is conducted using the intrinsic conditional autoregressive prior. The model was applied to breast, colorectal, and lung cancer data from the Queensland Cancer Registry across 478 geographical areas. Advantages of this approach include the ease of including more realistic complexity, the feasibility of using individual-level input data, and the capacity to conduct overall, cause-specific, and relative survival analysis within the same framework. Spatial flexible parametric survival models have great potential for exploring small-area survival inequalities, and we hope to stimulate further use of these models within wider contexts. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Objectives: Risk factors for residential fire death (young age, minority race/ethnicity, and low socioeconomic status) are common among urban pediatric emergency department (ED) patients. Community-based resources are available in our region to provide free smoke detector installation. The objective of our study was to describe awareness of these resources and home fire safety practices in this vulnerable population., Methods: In this cross-sectional study, a brief survey was administered to a convenience sample of caregivers accompanying patients 19 years of age or younger in an urban pediatric ED in Washington, DC. Survey contents focused on participant knowledge of available community-based resources and risk factors for residential fire injury., Results: Five hundred eleven eligible caregivers were approached, and 401 (78.5%) agreed to participate. Patients accompanying the caregivers were 48% male, 77% African American, and had a mean (SD) age of 6.5 (5.9) years. Of study participants, 256 (63.8%) lived with children younger than 5 years. When asked about available community-based resources for smoke detectors, 240 (59.9%) were unaware of these programs, 319 (79.6%) were interested in participating, and 221 (55.1%) enrolled. Presence of a home smoke detector was reported by 396 respondents (98.7%); however, 346 (86.3%) reported testing these less often than monthly. Two hundred fifty-six 256 (63.8%) lacked a carbon monoxide detector, and 202 (50.4%) had no fire escape plan. Sixty-five (16%) reported indoor smoking, and 92 (22.9%) reported space heater use., Conclusions: In this urban pediatric ED population, there is limited awareness of community-based resources but high rates of interest in participating once informed. Whereas the self-reported prevalence of home smoke detectors is high in our study population, other fire safety practices are suboptimal.

Genetic susceptibility and environmental exposure both play an important role in the aetiology of many diseases. Case-control studies are often the first choice to explore the joint influence of genetic and environmental factors on the risk of developing a rare disease. In practice, however, such studies may have limited power, especially when susceptibility genes are rare and exposure distributions are highly skewed. We propose a variant of the classical case-control study, the exposure enriched case-control (EECC) design, where not only cases, but also high (or low) exposed individuals are oversampled, depending on the skewness of the exposure distribution. Of course, a traditional logistic regression model is no longer valid and results in biased parameter estimation. We show that addition of a simple covariate to the regression model removes this bias and yields reliable estimates of main and interaction effects of interest. We also discuss optimal design, showing that judicious oversampling of high/low exposed individuals can boost study power considerably. We illustrate our results using data from a study involving arsenic exposure and detoxification genes in Bangladesh., Competing Interests: None, (© 2016 WILEY PERIODICALS, INC.)

Spatial data have become increasingly common in epidemiology and public health research thanks to advances in GIS (Geographic Information Systems) technology. In health research, for example, it is common for epidemiologists to incorporate geographically indexed data into their studies. In practice, however, the spatially defined covariates are often measured with error. Naive estimators of regression coefficients are attenuated if measurement error is ignored. Moreover, the classical measurement error theory is inapplicable in the context of spatial modeling because of the presence of spatial correlation among the observations. We propose a semiparametric regression approach to obtain bias-corrected estimates of regression parameters and derive their large sample properties. We evaluate the performance of the proposed method through simulation studies and illustrate using data on Ischemic Heart Disease (IHD). Both simulation and practical application demonstrate that the proposed method can be effective in practice., (© 2016, The International Biometric Society.)

Objectives: Children with public insurance are less likely than children with private insurance to obtain follow-up care after emergency department (ED) care. This study aimed to determine if specific demographic and clinical factors are associated with aftercare compliance in a population of publicly insured pediatric ED patients with orthopedic injuries., Methods: This was a retrospective case-control study of Washington, DC, children aged 0 to 17 years with public insurance discharged with isolated forearm fractures from the Children's National Medical Center ED from 2003 to 2006. Bivariable analyses and multivariable logistic regression were performed to measure the association between sociodemographic variables and failure to follow up., Results: Six hundred children met the inclusion criteria. The overall cohort was 63.7% male and 81.7% African American, with a mean age of 8.8 (SE, 0.2) years. Overall, 85.7% of patients went to a follow-up orthopedic appointment, and 68.2% of patients had timely orthopedic follow-up, defined as 14 days or less after discharge from the ED. Treatment with orthopedic reduction (adjusted odds ratio [OR], 2.0 [1.33-2.93]) was positively associated with timely orthopedic follow-up, whereas older age (adjusted OR, 0.9 [0.88-0.97]) was significantly associated with failure to follow up. In the subset of patients who required orthopedic reduction in the ED, older age was significantly associated with failure to follow up (adjusted OR, 0.80 [0.74-0.94])., Conclusions: Mild fracture severity is associated with lack of orthopedic follow-up for patients with public insurance. Older age was associated with lack of follow-up, even in the subgroup with severe fractures. Targeted interventions to improve orthopedic aftercare compliance should focus on older patients with severe forearm fractures.

Background: Medical resuscitations of critically ill children in the emergency department are stressful events requiring a coordinated team effort. Current guidelines recommend debriefing after such events to improve future performance. Debriefing practices within pediatric emergency departments by pediatric emergency medicine (PEM) fellows in the United States has not been studied., Objective: The aim of this study was to describe the current debriefing experience of PEM fellows in the United States., Methods: A 10-item, anonymous questionnaire regarding debriefing characteristics was distributed to fellows in US Accreditation Council for Graduate Medical Education-accredited PEM programs via e-mail and paper format from December 2011 to March 2012. Results were summarized using descriptive statistics., Results: Of 393 eligible PEM fellows, 201 (51.1%) completed the survey. The 201 respondents included 82 first-year fellows (40.8%), 71 second-year fellows (35.3%), and 48 third-year fellows (23.9%). Ninety-nine percent had participated in medical resuscitations during their fellowship training, yet 88.0% reported no formal teaching on how to debrief. There was wide variability in the format and timing of debriefings. The majority of debriefings were led by PEM attending physicians (65.5%) and PEM fellows (19.6%). Most (91.5%) of the fellows indicated they would like further education about debriefing., Conclusions: The majority of PEM fellows do not receive formal training on how to debrief after a critical event and may have limited experience in leading debriefings. Debriefing training should be considered part of the educational curriculum during PEM fellowship.

Background: Preventing risk factor exposure is vital to reduce the high burden from lung cancer. The leading risk factor for developing lung cancer is tobacco smoking. In Australia, despite apparent success in reducing smoking prevalence, there is limited information on small area patterns and small area temporal trends. We sought to estimate spatio-temporal patterns for lung cancer risk factors using routinely collected population-based cancer data., Methods: The analysis used a Bayesian shared component spatio-temporal model, with male and female lung cancer included separately. The shared component reflected lung cancer risk factors, and was modelled over 477 statistical local areas (SLAs) and 15 years in Queensland, Australia. Analyses were also run adjusting for area-level socioeconomic disadvantage, Indigenous population composition, or remoteness., Results: Strong spatial patterns were observed in the underlying risk factor estimates for both males (median Relative Risk (RR) across SLAs compared to the Queensland average ranged from 0.48 to 2.00) and females (median RR range across SLAs 0.53-1.80), with high risks observed in many remote areas. Strong temporal trends were also observed. Males showed a decrease in the underlying risk across time, while females showed an increase followed by a decrease in the final 2 years. These patterns were largely consistent across each SLA. The high underlying risk estimates observed among disadvantaged, remote and indigenous areas decreased after adjustment, particularly among females., Conclusion: The modelled underlying risks appeared to reflect previous smoking prevalence, with a lag period of around 30 years, consistent with the time taken to develop lung cancer. The consistent temporal trends in lung cancer risk factors across small areas support the hypothesis that past interventions have been equally effective across the state. However, this also means that spatial inequalities have remained unaddressed, highlighting the potential for future interventions, particularly among remote areas., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: High weight status is associated with increased forearm fracture risk but its relationship to severity of fracture has not been evaluated. We compared the epidemiology of children's forearm fractures treated with fracture reduction to those not treated with reduction, hypothesizing that high weight status would be significantly associated with need for reduction., Methods: This is a case-control study including Washington, DC children, ages 2 to 17 years, treated for isolated forearm fractures in an urban, tertiary care pediatric emergency department from 2003 to 2006. Descriptive statistics and logistic regression were conducted to compare patients with forearm fracture reductions to nonintervention controls., Results: Of 888 forearm fractures, 330 (37.2%) required reduction (cases) whereas 558 (64.8%) did not (controls). Cases were more likely than controls to be male [adjusted odds ratio, 1.67 (95% confidence interval, 1.11-2.50)] and to have experienced a more severe mechanism of trauma [adjusted odds ratio, 2.11 (95% confidence interval, 1.14-3.90)]. The groups did not differ in weight status, age, or race/ethnicity., Conclusions: The need for reduction among children with forearm fractures is significantly associated with male sex and major mechanisms of trauma but not with high weight status. Strategies to reduce severe forearm fractures should focus on preventing major mechanisms of trauma.

Calcium crystal arthritis is often unrecognized, poorly managed, and few effective therapies are available. The most common types of calcium crystals causing musculoskeletal syndromes are calcium pyrophosphate (CPP) and basic calcium phosphate (BCP). Associated syndromes have different clinical presentations and divergent management strategies. Acute CPP arthritis is treated similarly to acute gouty arthritis, whereas chronic CPP and BCP arthropathy may respond to strategies used for osteoarthritis. Calcific tendonitis is treated with a variety of interventions designed to dissolve BCP crystals. A better understanding of the causes and larger well-planned trials of current therapies will lead to improved care., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: Accumulation of excess extracellular inorganic pyrophosphate leads to calcium pyrophosphate dihydrate (CPPD) crystal formation in articular cartilage. CPPD crystal formation occurs near morphologically abnormal chondrocytes resembling hypertrophic chondrocytes. The ANK protein was recently implicated as an important factor in the transport of intracellular inorganic pyrophosphate across the cell membrane. We characterized ANK in joint tissues from patients with and without CPPD deposition and correlated the presence of ANK with markers of chondrocyte hypertrophy., Methods: Articular tissues were obtained from 24 patients with CPPD crystal deposition disease, 11 patients with osteoarthritis (OA) without crystals, and 6 controls. We determined the number of ANK-positive cells in joint tissues using immunohistochemistry and in situ hybridization, and correlated ANK positivity with markers of chondrocyte hypertrophy including Runx2, type X collagen, osteopontin (OPN), and osteocalcin (OCN)., Results: ANK was detected in synoviocytes, chondrocytes, osteoblasts, and osteocytes. ANK was seen extracellularly only in the matrix of cartilage and meniscus. The number of ANK-positive cells was significantly higher in CPPD than in OA or normal joint tissues. The amount and intensity of ANK immunoreactivity reached maximum levels in the large chondrocytes around crystal deposits. ANK was similarly distributed to and significantly correlated with Runx2, type X collagen, OPN, and OCN., Conclusion: ANK levels were higher in articular tissues from patients with CPPD deposition. ANK was concentrated around crystal deposits and correlated with markers of chondrocyte hypertrophy. These findings support a role for ANK in CPPD crystal formation in cartilage.

Introduction: Extracellular ATP (eATP) is released by articular chondrocytes under physiological and pathological conditions. High eATP levels cause pathologic calcification, damage cartilage, and mediate pain. We recently showed that stable over-expression of the progressive ankylosis gene product, ANK, increased chondrocyte eATP levels, but the mechanisms of this effect remained unexplored. The purpose of this work was to further investigate mechanisms of eATP efflux in primary articular chondrocytes and to better define the role of ANK in this process., Methods: We measured eATP levels using a bioluminescence-based assay in adult porcine articular chondrocyte media with or without a 10 minute exposure to hypotonic stress. siRNAs for known ATP membrane transporters and pharmacologic inhibitors of ATP egress pathways were used to identify participants involved in chondrocyte eATP release., Results: eATP levels increased after exposure to hypotonic media in a calcium-dependent manner in monolayer and 3-dimensional agarose gel cultures (p < 0.001). A potent transient receptor potential vanilloid 4 (TRPV4) agonist mimicked the effects of hypotonic media. ANK siRNA suppressed basal (p < 0.01) and hypotonically-stressed (p < 0.001) ATP levels. This effect was not mediated by altered extracellular pyrophosphate (ePPi) levels, and was mimicked by the ANK inhibitor, probenecid (p < 0.001). The P2X7/4 receptor inhibitor Brilliant Blue G also suppressed eATP efflux induced by hypotonic media (p < 0.001), while ivermectin, a P2X4 receptor stimulant, increased eATP levels (p < 0.001). Pharmacologic inhibitors of hemichannels, maxianion channels and other volume-sensitive eATP efflux pathways did not suppress eATP levels., Conclusions: These findings implicate ANK and P2X7/4 receptors in chondrocyte eATP efflux. Understanding the mechanisms of eATP efflux may result in novel therapies for calcium crystal arthritis and osteoarthritis.

Digital imaging combined with picture archiving and communication system (PACS) access allows detailed image retrieval and magnification. Calcium pyrophosphate dihydrate (CPPD) crystals preferentially deposit in fibrocartilages, the cartilage of the acromioclavicular (AC) joint being one such structure. We sought to determine if examination of the AC joints on magnified PACS imaging of chest films would be useful in identifying chondrocalcinosis (CC). Retrospective radiographic readings and chart reviews involving 1,920 patients aged 50 or more who had routine outpatient chest radiographs over a 4-month period were performed. Knee radiographs were available for comparison in 489 patients. Medical records were reviewed to abstract demographics, chest film reports, and diagnoses. AC joint CC was identified in 1.1 % (21/1,920) of consecutive chest films. Patients with AC joint CC were 75 years of age versus 65.4 in those without CC (p < 0.0002). Four hundred eighty-nine patients had knee films. Six of these patients had AC joint CC, and of these, five also had knee CC (83 %). Of the 483 without AC joint CC, 62 (12 %) had knee CC (p = 0.002). Patients with AC joint CC were more likely to have a recorded history of CPPD crystal deposition disease than those without AC joint CC (14 versus 1 %, p = 0.0017). The prevalence of AC joint CC increases with age and is associated with knee CC. A finding of AC joint CC should heighten suspicion of pseudogout or secondary osteoarthritis in appropriate clinical settings and, in a young patient, should alert the clinician to the possibility of an associated metabolic condition.

Background: Effects of neighborhood contextual features have been found for many diseases, including bone fractures in adults. Our study objective was to evaluate the association between neighborhood characteristics and pediatric bone fracture rates. We hypothesized that neighborhood indices of deprivation would be associated with higher fracture rates., Materials and Methods: Pediatric bone fracture cases treated at a tertiary, academic, urban pediatric emergency department between 2003 and 2006 were mapped to census block groups using geographical information systems software. Fracture rates were calculated as fractures per 1000 children in each census block. Exploratory factor analysis of socioeconomic indicators was performed using 2000 census block data. Factor scores were used to predict odds of bone fracture at the individual level while adjusting for mean age, sex composition, and race/ethnicity composition at census block level using our sample data., Results: We analyzed 3764 fracture visits in 3557 patients representing 349 distinct census blocks groups. Fracture rates among census blocks ranged from 0 to 207 per 1000 children/study period. Logistic regression modeling identified 2 factors (race/education and large families) associated with increased fracture risk. Census variables reflecting African American race, laborer/service industry employment, long-term block group residence, and lower education levels strongly loaded on the race/education factor. The large families factor indicated the children-to-families ratio within the block group. The poverty factor was not independently associated with fracture risk., Conclusions: Thus, neighborhood characteristics are associated with risk for fractures in children. These results can help inform translational efforts to develop targeted strategies for bone fracture prevention in children.

Fully functional T cells are necessary for the maintenance of protective immunity during chronic infections. However, activated T cells often undergo apoptosis or exhaustion upon chronic stimulation mediated by Ag or inflammation. T cell attrition can be compensated for by the production of thymus-derived T cells, although the new naive T cells must undergo T cell priming and differentiation under conditions different from those encountered during acute infection. We used a murine model of Mycobacterium tuberculosis infection to address how the activation and differentiation of new thymic emigrants is affected by chronic inflammation, as well as whether the newly developed effector T cells help to maintain peripheral T cell responses. Although new thymic emigrants contributed to the peripheral T cell response early during acute M. tuberculosis infection, the relative contribution of new effector T cells to the peripheral CD4 and CD8 T cell pools declined during chronic infection. The decline in new T cell recruitment was a consequence of quantitative and/or qualitative changes in Ag presentation, because during chronic infection both the priming and expansion of naive T cells were inefficient. Thus, although thymic tolerance is not a major factor that limits protective T cell responses, the chronic environment does not efficiently support naive T cell priming and accumulation during M. tuberculosis infection. These studies support our previous findings that long-term protective T cell responses can be maintained indefinitely in the periphery, but also suggest that the perturbation of homeostasis during chronic inflammatory responses may elicit immune pathology mediated by new T cells.

Objective: To determine whether African American children with forearm fractures have decreased bone mineral density and an increased prevalence of vitamin D deficiency (serum 25-hydroxyvitamin D level ≤ 20 ng/mL) compared with fracture-free control patients., Methods: This case-control study in African American children, aged 5 to 9 years, included case patients with forearm fracture and control patients without fracture. Evaluation included measurement of bone mineral density and serum 25-hydroxyvitamin D level. Univariable and multivariable analyses were used to test for associations between fracture status and 2 measures of bone health (bone mineral density and 25-hydroxyvitamin D level) while controlling for other potential confounders., Results: The final sample included 76 case and 74 control patients. There were no significant differences between case and control patients in age, gender, parental education level, enrollment season, outdoor play time, height, or mean dietary calcium nutrient density. Cases were more likely than control patients to be overweight (49.3% vs 31.4%, P = .03). Compared with control patients, case patients had lower whole body z scores for bone mineral density (0.62 ± 0.96 vs 0.98 ± 1.09; adjusted odds ratio 0.38 [0.20-0.72]) and were more likely to be vitamin D deficient (47.1% vs 40.8%; adjusted odds ratio 3.46 [1.09-10.94])., Conclusions: These data support an association of lower bone mineral density and vitamin D deficiency with increased odds of forearm fracture among African American children. Because suboptimal childhood bone health also negatively impacts adult bone health, interventions to increase bone mineral density and correct vitamin D deficiency are indicated in this population to provide short-term and long-term benefits.

We sought to investigate the relationship between newly identified genetic variants and vitamin D levels and fracture risk in healthy African American (black) children. This case-control study included children of both sexes, ages 5 to 9 years, with and without forearm fractures. Serum 25-hydroxy vitamin D levels, bone mineral density, body mass index, and calcium/vitamin D intake were measured in 130 individuals (n = 60 cases and n = 70 controls). The 5 variants tested were located in the GC gene (rs2282679), in the NADSYN1 gene (rs12785878 and rs3829251), and in the promoter region of the CYP2R1 gene (rs2060793 and rs104741657). Associations between single nucleotide polymorphisms (SNPs) and vitamin D levels were tested using an analysis of covariance. Associations between SNPs and fracture status were tested using logistic regression. The GC gene variant was associated with vitamin D levels (P = 0.038). None of the SNPs were associated with fracture status in young blacks. These results suggest that the variants tested, which are associated with circulating vitamin D levels in whites, are not associated with fracture status in healthy black children. Additional research is required to discover the genetics of fracture risk in blacks.