Vosoritide treatment for children with hypochondroplasia: a phase 2 trial.

Background: Hypochondroplasia is a rare autosomal dominant skeletal dysplasia due to activating variants in FGFR3. It presents with disproportionate short stature with a wide range of clinical severity. There are currently no approved medications to treat short stature in children with hypochondroplasia. Vosoritide is a C-type natriuretic peptide analog that was recently approved for improving growth in children with achondroplasia. We aimed to evaluate the safety and efficacy of vosoritide in children with hypochondroplasia. Methods: We conducted a single-arm, phase 2, open-label trial at a single centre in the USA and enrolled 26 children with hypochondroplasia. The trial consists of a 6-month observation period to establish a baseline annualized growth velocity followed by a 12-month intervention period during which vosoritide is administered daily via subcutaneous injection at a dose of 15 µg/kg/day. The trial's co-primary endpoints included the incidence of adverse events and the change from baseline in age-sex standardized annualized growth velocity and height standardized deviation score (SDS) after 12 months of treatment. This trial is registered with ClinicalTrials.gov (NCT04219007). Findings: Twenty-four participants with a mean age of 5.86 years received vosoritide therapy. The first participant was enrolled on August 4, 2020, and the final participant completed the 18-month trial on September 8, 2023. Vosoritide was well tolerated with no treatment-related serious adverse events. Injection site reactions occurred in 83.3% of participants. No participants discontinued therapy due to an adverse event. Annualized growth velocity increased by 2.26 standard deviations (SD) and height SDS increased by 0.36 SD during the treatment period versus the observation period. Hypochondroplasia specific height SDS increased by 0.38 SD. There was a 1.81 cm/year increase in absolute annualized growth velocity. Interpretation: Vosoritide was safe and effective in increasing growth velocity in children with hypochondroplasia. Efficacy was similar to what has been reported in children with achondroplasia. Funding: This study was supported by an investigator-initiated grant from BioMarin Pharmaceutical.

Test Accuracy of the Screening Tool for Early Predictors of Post-traumatic Stress Disorder for Post-injury Mental Health in a Managed-Medicaid Population.

OBJECTIVE: To determine the Screening Tool for Early Predictors of Post-Traumatic Stress Disorder (STEPP) test accuracy in identifying children with new mental health diagnoses and psychotropic medications prescribed within 12 months after unintentional injuries in a managed-Medicaid population. STUDY DESIGN: We conducted a secondary analysis of a retrospective cohort that investigated mental health diagnoses and psychotropic medications pre- and post-injury in children ≤18 years of age treated at a pediatric trauma center from 2005 to 2015 (n = 2208). For this study, we analyzed children with STEPP scores from their injury admission (n = 85). For children without previous mental health diagnoses or psychotropic prescriptions, we calculated the sensitivity, specificity, and positive and negative predictive values for the child and parent STEPP. RESULTS: Of 78 children without previous diagnoses, 12 had post-injury mental health diagnoses. Of 68 children without previous psychotropic medication use, 10 had psychotropic medications prescribed. The child STEPP sensitivity was 8.3% for mental health diagnoses (95% CI 0.2, 38.5) and 10% for psychotropic medications (95% CI 0.3, 44.5). The child STEPP specificity was 77.3% for mental health diagnoses (95% CI 65.3, 86.7) and 75.9% for psychotropic medication (95% CI 62.8, 86.1). CONCLUSIONS: We found that the STEPP performed poorly in identifying children who received new mental health diagnoses and new psychotropic medications following injury.

Nutritional Considerations of the Gluten-Free Diet.

Celiac disease (CD) is an autoimmune-related disease causing inflammation in the small intestine triggered by the ingestion of gluten in the diet. The gluten-free diet (GFD) is the only treatment. Nutritional deficiencies of macronutrients and micronutrients are frequently found in untreated or newly diagnosed CD. A registered dietitian nutritionist is uniquely qualified to educate on the GFD and assess and support nutritional status at diagnosis and long term as well as helping patients with nonresponsive CD. Quality of life is important to address in individuals with CD because the GFD affects all aspects of life.

Characteristics of Neighborhoods Where Emergency Medical Services Encounter Children at Risk for Maltreatment.

Objective: The objective of this study was to determine if neighborhood rates of pediatric Emergency Medical Services (EMS) encounters correlate with rates of child maltreatment reporting and if there are neighborhood-level risk factors for EMS encountering children with maltreatment reports. Methods: We conducted a retrospective cohort study using the electronic medical records of children ages <18 years who had Columbus Division of Fire EMS encounters between 2011 and 2015. We used Nationwide Children's Hospital electronic medical records to identify child maltreatment reports. The EMS scene addresses and home addresses associated with maltreatment reports were geocoded independently and rates for each Census tract were calculated. The maltreatment reports were matched to the EMS encounters using name, gender, and date of birth. Rates of EMS encounters with children that had a maltreatment report were calculated for each Census tract. Census tract demographic information was obtained from the American Community Survey. Bayesian conditional autoregressive Poisson models were used to calculate rate ratios for census tract variables to determine their relationship to EMS encountering children with maltreatment reports. Results: A total of 44,002 EMS encounters and 4,298 maltreatment reports were included in the study. The Spearman correlation coefficient relating rates of EMS encounters to rates of maltreatment reports within census tracts was 0.72 (95% confidence interval, 0.65-0.77). Within the study period, a total of 1,134 EMS encounters were linked to 578 children with maltreatment reports. Poverty was the only independent risk factor for EMS encountering children with maltreatment reports. The multivariate analysis also identified protective factors, which included neighborhoods with higher proportions of residents who had bachelor's degrees, spoke a language other than English, and had the same residence the previous year. Conclusion: This study showed that in Franklin County, Ohio, neighborhoods with high EMS utilization had a strong positive correlation with areas that had high rates of child maltreatment reports. We also identified four neighborhood characteristics that were independently associated with EMS encountering children at risk for maltreatment (risk factor: poverty; protective factors: residents with college educations, non-English speaking households, and residents maintaining the same residence as the previous year).

Trends in US Emergency Department Visits for Pediatric Acute Ocular Injury.

Importance: There is a lack of literature describing the incidence of pediatric acute ocular injury and associated likelihood of vision loss in the United States. Understanding national pediatric eye injury trends may inform future efforts to prevent ocular trauma. Objective: To characterize pediatric acute ocular injury in the United States using data from a stratified, national sample of emergency department (ED) visits. Design, Setting, and Participants: A retrospective cohort study was conducted. Study participants received care at EDs included in the 2006 to 2014 Nationwide Emergency Department Sample, comprising 376 040 children aged 0 to 17 years with acute traumatic ocular injuries. Data were analyzed from June 2016 to March 2018. Exposures: International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes and external-cause-of-injury codes identified children with acute ocular injuries. Main Outcomes and Measures: Demographic and clinical characteristics of children with acute traumatic ocular injuries were collected and temporal trends in the incidence of ocular injuries by age, risk of vision loss, and mechanism of injury were explored. Results: In 2014, there were an estimated 163 431 (95% CI, 151 235-175 627) ED visits for pediatric acute ocular injury. Injured children were more often male (63.0%; 95% CI, 62.5-63.5) and in the youngest age category (birth to 4 years, 35.3%; 95% CI, 34.4-36.2; vs 10-14 years, 20.6%; 95% CI, 20.1-21.1). Injuries commonly resulted from a strike to the eye (22.5%; 95% CI, 21.3-23.8) and affected the adnexa (43.7%; 95% CI, 42.7-44.8). Most injuries had a low risk for vision loss (84.2%; 95% CI, 83.5-85.0), with only 1.3% (95% CI, 1.1-1.5) of injuries being high risk. Between 2006 and 2014, pediatric acute ocular injuries decreased by 26.1% (95% CI, -27.0 to -25.0). This decline existed across all patient demographic characteristics, injury patterns, and vision loss categories and for most mechanisms of injury. There were increases during the study in injuries related to sports (12.8%; 95% CI, 5.4-20.2) and household/domestic activities (20.7%; 95% CI, 16.2-25.2). The greatest decrease in high-risk injuries occurred with motor vehicle crashes (-79.8%; 95% CI, -85.8 to -74.9) and guns (-68.5%; 95% CI, -73.5 to -63.6). Conclusions and Relevance: This study demonstrated a decline in pediatric acute ocular injuries in the United States between 2006 and 2014. However, pediatric acute ocular injuries continue to be prevalent, and understanding these trends can help establish future prevention strategies.

Mental Health after Unintentional Injury in a Pediatric Managed-Medicaid Population.

OBJECTIVES: The purpose of this study was to compare the rates of mental health diagnoses and psychotropic prescriptions pre- and posthospitalization for injury in a managed-Medicaid population. We hypothesized that children have increased rates of mental health diagnoses and psychotropic prescriptions after injury. STUDY DESIGN: We investigated children (n = 2208) ≤18 years of age treated at a pediatric trauma center from 2005 to 2015 who were enrolled in a managed-Medicaid program at hospital admission and for at least 1 healthcare visit in the preceding year. We used Poisson regression models to estimate rates of mental health diagnoses and psychotropic prescriptions that occurred in the 12 months pre- and postinjury. RESULTS: The rate of mental health diagnoses preinjury was 95.9 per 1000 person-years, which increased to 156.7 per 1000 postinjury (rate ratio [RR] 1.63, 95% CI 1.39-1.92). Children ages 0-4 years with burns were more likely to have mental health diagnoses postinjury (race and ethnicity adjusted RR [aRR] 8.56, 95% CI 3.30-22.2). Children with head injuries were also more likely to have mental health diagnoses postinjury: ages 0-4 years (aRR 3.87, 95% CI 1.31-11.5); ages 5-9 (aRR 3.11, 95% CI 1.27-7.59); ages 10-14 (aRR 2.17, 95% CI 1.27-3.73); and ages 15-18 (aRR 5.37, 95% CI 2.12-13.6). The rate of psychotropic prescriptions preinjury was 121.7 per 1000 person-years and increased to 310.9 per 1000 postinjury (RR 2.55, 95% CI 2.26-2.89). CONCLUSIONS: We identified increased mental health diagnoses and psychotropic prescriptions in children following hospitalization for injury.

Impact of emergency preparedness exercise on performance.

The aim of this study was to investigate whether prior participation in preparedness exercises was predictive of better performance on objective measures of response. We conducted a statewide tabletop exercise that focused on a hazardous materials (HAZMAT) scenario and assessed performance using our developed evaluation tool. The evaluative score was analyzed in relation to the number of HAZMAT exercises in the past 3 years, participation in prior CHEMPACK-specific exercise, hospital size, teaching status of the hospital, preparedness training experience, and participants years of experience in preparedness activities. Hospitals that had participated in more exercises in the past 3 years performed significantly better than hospitals that had participated in fewer exercises. No significant differences were found between the performance of hospitals in relation to size, teaching status, preparedness training experience, and participants' years of experience in preparedness activities. Our results suggest that more frequent participation in exercises may result in improved overall response.

Effect of stimulus type on the eye movements of children.

PURPOSE: The authors investigated whether pictures elicit superior response rates and eye movement dynamics on saccade and pursuit tasks than do dots or spots of light and whether the need for more interesting stimuli is age dependent. METHODS: Using video eye tracking, horizontal eye movements were investigated in children and adults using dots and small colored pictures as stimuli. Saccade data were obtained from 61 people and pursuit data from 53 people, ages 3 to 30 years, with no known ocular, ocular motor, neurologic, or systemic disease. Saccadic stimuli were randomly presented in steps ranging in size from 5° to 30°. Pursuits at four velocities (5°/s, 10°/s, 20°/s, and 30°/s) were tested using step ramp stimuli. RESULTS: Picture targets result in age-dependent improvements in ocular motor responses compared with dots. With the exception of saccadic accuracy, the youngest children are most affected by the type of target. Adults are affected very little. For pictures, saccadic response rates (t((60)) = 4.30, P < 0.001), saccadic peak velocities (t((60)) = 2.24, P = 0.03), saccadic accuracy (t((59)) = 2.34, P = 0.02), and closed-loop pursuit gains (F((3,50)) = 2.86, P = 0.046) are higher. Saccadic error rates (t((60)) = 3.91, P < 0.001) and saccadic latencies (t((59)) = 9.5, P < 0.001) are lower with pictures. CONCLUSIONS: Stimulus characteristics can affect response rates and eye movement dynamics, particularly in young children. To avoid underestimation of eye movement performance in young children, it is important to use meaningful targets. Furthermore, when comparing the ocular motor performance of children across studies one must consider the type of stimuli used.

Diagnosing smallpox: would you know it if you saw it?

The intentional release of anthrax in the United States in 2001 and other recent acts of terrorism have highlighted the possibility of intentional release of smallpox by terrorists. Little is known about physicians' ability to diagnose smallpox, especially in the critical first days, when the potential for rapid control of transmission is greatest. During December 2002 and January 2003, primary care and emergency physicians at a large urban academic medical center were surveyed regarding the diagnosis and management of patients who present with vesicular rash illness. In addition to demographic and training-related questions, the questionnaire included items about perceived comfort in diagnosing and evaluating rashes, knowledge of the key differential diagnostic characteristics of chickenpox and smallpox, and the diagnostic interpretation of color photographs of patients with smallpox or chickenpox. Responses were summarized as a perceived comfort score, a differential diagnosis score, and a picture score. Of 266 eligible physicians, 178 (67%) responded. Of these, 95% thought clinicians need more education about bioterrorism; only 17% reported comfort in diagnosing smallpox. Although most physicians recognized pictures of smallpox and chickenpox, only 36% correctly answered 3 of 4 questions regarding differential diagnosis, an important aspect of identifying cases early. Those who were comfortable diagnosing rash illnesses had higher differential diagnosis scores. Strategies for bioterrorism-related training could take advantage of physicians' awareness of their own knowledge deficits.