MRI-informed muscle biopsies correlate MRI with pathology and DUX4 target gene expression in FSHD.

Facioscapulohumeral muscular dystrophy (FSHD) is a common, dominantly inherited disease caused by the epigenetic de-repression of the DUX4 gene, a transcription factor normally repressed in skeletal muscle. As targeted therapies are now possible in FSHD, a better understanding of the relationship between DUX4 activity, muscle pathology and muscle magnetic resonance imaging (MRI) changes is crucial both to understand disease mechanisms and for the design of future clinical trials. Here, we performed MRIs of the lower extremities in 36 individuals with FSHD, followed by needle muscle biopsies in safely accessible muscles. We examined the correlation between MRI characteristics, muscle pathology and expression of DUX4 target genes. Results show that the presence of elevated MRI short tau inversion recovery signal has substantial predictive value in identifying muscles with active disease as determined by histopathology and DUX4 target gene expression. In addition, DUX4 target gene expression was detected only in FSHD-affected muscles and not in control muscles. These results support the use of MRI to identify FSHD muscles most likely to have active disease and higher levels of DUX4 target gene expression and might be useful in early phase therapeutic trials to demonstrate target engagement in therapies aiming to suppress DUX4 expression.

Ambulatory Blood Pressure and Endothelial Dysfunction in Hematopoietic Cell Transplantation Recipients.

Hematopoietic cell transplantation (HCT) is a common treatment for many disorders. Albuminuria post-HCT, which may represent endothelial injury or inflammation from graft- versus-host disease, increases the risk of chronic kidney disease and nonrelapse mortality at 1 year. HCT recipients also have abnormal blood pressure (BP) and increased rates of cardiovascular complications. We sought to determine the relationships among albuminuria, endothelial dysfunction, and BP in HCT recipients. Patients age ≥12 years who underwent their first allogeneic HCT between 2012 and 2015 and survived through day 80 post-HCT were eligible. Peripheral endothelial function was assessed using the EndoPAT2000 device at day 80 along with 24-hour ambulatory BP monitoring (ABPM). Clinical and laboratory data were collected along with a urine sample for calculation of the albumin-to-creatinine ratio. Both logistic and linear regression analyses were used to identify associations between EndoPAT score and clinical variables. Sixty patients (median age, 48 years; range, 14 to 69 years) completed the study. The median EndoPAT score was 2.05 (range, 1.02 to 4.45), and 17 patients (28%) had abnormal endothelial function. Forty-two patients (72%) had ambulatory hypertension (HTN), and 38 (63%) had blunted nocturnal dipping. HTN on ABPM (P = .045) and blunted nocturnal dipping (P = .04) were associated with a lower EndoPAT score. Albuminuria was not associated with EndoPAT score. There was a lack of agreement between our clinical definition of HTN (office BP and/or use of medications) and ABPM results (P = .04). We did not find an association between lower EndoPAT scores and albuminuria, but did find an association between an abnormal nocturnal dip and HTN diagnosed by ABPM. This suggests that albuminuria may reflect local endothelial injury and inflammation rather than a systemic process. Office BP readings do not accurately reflect true BP, suggesting that 24-hour ABPM studies are needed to diagnose and treat HTN appropriately.

MRI change metrics of facioscapulohumeral muscular dystrophy: Stir and T1.

INTRODUCTION: MRI evaluation in facioscapulohumeral muscular dystrophy (FSHD) demonstrates fatty replacement and inflammation/edema in muscle. Our previous work demonstrated short T1 inversion recovery (STIR)-hyperintense (STIR+) signal in muscle 2 years before fatty replacement. We evaluated leg muscle STIR changes and fatty replacement within 14 months. METHODS: FSHD subjects received 2 MRI scans of thigh and calf over a 6.9- to 13.8-month interval. Quality of life measures were collected. One Radiologist rated muscle changes on a semi-quantitative scale. RESULTS: Fifteen subjects completed longitudinal imaging. Four STIR + muscles and 3 STIR-normal (STIR-) muscles were rated as progressing to fatty tissue over the study period. DISCUSSION: STIR + muscles with confluent regions of fat at baseline increased more in fat, while STIR- muscles had increases in septal-fat over the study period. These changes may reflect two phases of FSHD, demonstrating MRI sensitivity is weighted toward gross pathological phases of the disease. Muscle Nerve 57: 905-912, 2018.

Variability in Management of First Cerebrospinal Fluid Shunt Infection: A Prospective Multi-Institutional Observational Cohort Study.

OBJECTIVES: To describe the variation in approaches to surgical and antibiotic treatment for first cerebrospinal fluid (CSF) shunt infection and adherence to Infectious Diseases Society of America (IDSA) guidelines. STUDY DESIGN: We conducted a prospective cohort study of children undergoing treatment for first CSF infection at 7 Hydrocephalus Clinical Research Network hospitals from April 2008 through December 2012. Univariate analyses were performed to describe the study population. RESULTS: A total of 151 children underwent treatment for first CSF shunt-related infection. Most children had undergone initial CSF shunt placement before the age of 6 months (n = 98, 65%). Median time to infection after shunt surgery was 28 days (IQR 15-52 days). Surgical management was most often shunt removal with interim external ventricular drain placement, followed by new shunt insertion (n = 122, 81%). Median time from first negative CSF culture to final surgical procedure was 14 days (IQR 10-21 days). Median duration of intravenous (IV) antibiotic use duration was 19 days (IQR 12-28 days). For 84 infections addressed by IDSA guidelines, 7 (8%) met guidelines and 61 (73%) had longer duration of IV antibiotic use than recommended. CONCLUSIONS: Surgical treatment for infection frequently adheres to IDSA guidelines of shunt removal with external ventricular drain placement followed by new shunt insertion. However, duration of IV antibiotic use in CSF shunt infection treatment was consistently longer than recommended by the 2004 IDSA guidelines.

Pediatric Nurse Performance on a Medication Dosage Calculation Assessment Tool.

UNLABELLED: Nurses who care for children must be competent to perform medication dosage calculations because most pediatric doses are weight based and obtained from adult formulations. PURPOSE: The purpose of the study was to describe and compare nurse performance on a medication dosage calculation assessment tool, considering work unit, years experience, and certification status. DESIGN: A secondary analysis of data from 851 Registered Nurses (RN) was completed. Multiple regression was used to model the effect of work unit, certification, and experience on score. FINDINGS: The mean assessment tool score was 92.4 (47-100). The work unit and the interaction between certification status and experience were significant in relation to score on the calculation assessment.

Development of a Scoring Tool for Chronic Nonbacterial Osteomyelitis Magnetic Resonance Imaging and Evaluation of its Interrater Reliability.

OBJECTIVE: Serial magnetic resonance imaging (MRI) examinations are often needed in chronic nonbacterial osteomyelitis (CNO) to determine the objective response to treatment. Our objectives in this study were (1) to develop a consensus-based MRI scoring tool for clinical and research use in CNO; and (2) to evaluate interrater reliability and agreement using whole-body (WB)-MRI from children with CNO. METHODS: Eleven pediatric radiologists discussed definitions and grading of signal intensity, size of signal abnormality within bone marrow, and associated features on MRI through monthly conference calls and a consensus meeting, using a nominal group technique in July 2017. WB-MRI scans from children with CNO were deidentified for training reading and an interrater reliability study. The reading by each radiologist was conducted in a randomized order. Interrater reliability for abnormal signal and severity were assessed using free-marginal κ statistics. RESULTS: Radiologists reached a consensus on grading CNO-specific MRI findings and on describing bone units based on anatomy. A total of 45 sets of WB-MRI scans, including 4 sets of non-CNO MRI examinations, were selected for the final reading. The mean κ of each category of bones was > 0.7 with majority > 0.9 demonstrating substantial/almost perfect interrater reliability of readings among radiologists. The agreement on signal intensity and the size of signal abnormality within the most commonly affected bones (femur and tibia) were lower than those of other bones. CONCLUSION: The chronic nonbacterial osteomyelitis magnetic resonance imaging scoring (CROMRIS) tool is a comprehensive standardized scoring tool for MRI in children with CNO. Our interrater study demonstrated good interrater reliability and agreement of readings.

Linkage of the CF foundation patient registry with the pediatric health information system database.

INTRODUCTION: The Cystic Fibrosis Foundation Patient Registry (CFFPR) contains clinical and demographic data from ∼85% of US cystic fibrosis (CF) patients across 120 care centers, but lacks robust inpatient hospitalization data. In contrast, the Pediatric Health Information System (PHIS) database includes inpatient clinical and resource utilization data from 49 US children's hospitals. The creation of a linked CFFPR-PHIS dataset can uniquely address questions related to in-hospital pediatric CF treatment and management. We assessed the feasibility of linking the CFFPR and PHIS databases and determined if successfully linked CF patients were generalizable to unlinked patients. METHODS: CF patients ≤21 years were eligible for linkage. The CFFPR and PHIS databases were linked at the patient level using indirect identifiers in a stepwise, deterministic, linkage approach. A validation cohort was created using a subset of patients to determine linkage accuracy. Clinical and demographic characteristics between linked and unlinked patients were compared to determine generalizability of the linked cohort. RESULTS: Of the 11 735 CF patients eligible for linkage from January 1st, 2005 through December 31st, 2016, 10 660 (91%) were successfully linked. Results of our single center validation cohort illustrated 100% accuracy. When compared to unlinked CF patients, fewer linked patients were born before 1990, more were Hispanic, and more were from West-affiliated PHIS hospitals. Otherwise, no clinically meaningful differences were seen between linked and unlinked CF patients. CONCLUSIONS: We demonstrated successful linkage of the CFFPR and PHIS databases, and created a large generalizable pediatric CF cohort for use in CF-related research.

Evaluation of a Modified Objective Structured Assessment of Technical Skills Tool for the Assessment of Pediatric Laceration Repair Performance.

Introduction The Accreditation Council for Graduate Medical Education (ACGME) has developed milestones including procedural skills under the core competency of patient care. Progress in training is expected to be monitored by residency programs. To our knowledge, there exists no tool to evaluate pediatric resident laceration repair performance. Methods The Objective Structured Assessment of Technical Skills was adapted to evaluate resident laceration repair performance using two components: a global rating scale (GRS) and a checklist. Pediatric and family medicine residents at a tertiary care children's hospital were filmed performing a simulated laceration repair. Videos were evaluated by at least five physicians trained in laceration repair. Concordance correlation coefficients (CCC) were calculated for the GRS and checklist scores. Scores for each resident were compared across levels of training and procedural experience. Spearman's rank order correlations were calculated to compare the checklist and GRS. Results Thirty residents were filmed performing laceration repair procedures. The CCC showed fair concordance across reviewers for the checklist (0.55, 95% CI: 0.38-0.69) and the GRS (0.53, 95% CI: 0.36-0.67). There was no significant difference in scores by self-reported experience or training level. There was correlation between the median GRS and checklist scores (Spearman ρ = 0.730, p < .001). Conclusions A novel tool to evaluate resident laceration repair performance in a pediatric emergency department showed fair agreement across reviewers. The study tool is not precise enough for summative evaluation; however, it can be used to distinguish between trainees who have and have not attained competence in laceration repair for formative feedback.

A Pilot Study of Infrared Thermal Imaging to Detect Active Bone Lesions in Children With Chronic Nonbacterial Osteomyelitis.

OBJECTIVE: Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease. An inexpensive and rapid imaging tool, infrared thermal imaging, was evaluated for its utility to detect active bone lesions in extremities of children with CNO. METHODS: Children with suspected active CNO and healthy controls were enrolled. All subjects underwent infrared thermal imaging of the lower extremities. Patients in the CNO group also received a magnetic resonance imaging (MRI) examination. Hyperintensity within bone marrow on a fluid-sensitive T2-weighted MRI sequence was considered confirmatory for inflammation. Infrared thermal data were analyzed using custom software by dividing the leg below the knee into 3 equal segments longitudinally and adding the distal femur segment as an equal length above the knee. Median and 95th percentile temperatures were recorded for each leg segment. Temperature differences between inflamed and uninflamed segments in all subjects (both intersubject and intrasubject) were evaluated using a linear mixed-effects model. RESULTS: Thirty children in the suspected/known CNO group and 31 healthy children were enrolled. In the healthy control group, males had significantly higher temperature in their lower extremities than females (P < 0.05). There was no difference in temperature detected between inflamed leg segments of patients with CNO versus uninflamed leg segments of the healthy control group. However, within the CNO group, significantly higher temperatures were detected for inflamed versus uninflamed distal tibia/fibula segments (P < 0.01). CONCLUSION: Children with active CNO lesions in the distal tibia/fibula exhibited higher regional temperatures on average than healthy extremities. Larger studies are warranted to further evaluate the clinical utility of infrared thermal imaging for CNO detection.

Performance of the Silverman Andersen Respiratory Severity Score in predicting PCO2 and respiratory support in newborns: a prospective cohort study.

OBJECTIVE: To determine if the Silverman Andersen respiratory severity score, which is assessed by physical exam, within 1 h of birth is associated with elevated carbon dioxide level and/or the need for increased respiratory support. STUDY DESIGN: Prospective cohort study including 140 neonates scored within 1 h of birth. We report respiratory scores and their association with carbon dioxide and respiratory support within 24 h. RESULTS: Carbon dioxide level correlated with respiratory score (n = 33, r = 0.35, p = 0.045). However, mean carbon dioxide for patients with score <5 vs. ≥5 did not differ significantly (56 vs. 67, p = 0.095). Patients with respiratory scores ≥5 had respiratory support increased within 24 h more often than those with scores <5 (79% vs. 28%, p < 0.001). CONCLUSION: The Silverman Andersen respiratory severity score may be valuable for predicting need for escalation of respiratory support and facilitate decision making for transfer in low-resource settings.

Reinfection after treatment of first cerebrospinal fluid shunt infection: a prospective observational cohort study.

OBJECTIVE CSF shunt infection requires both surgical and antibiotic treatment. Surgical treatment includes either total shunt removal with external ventricular drain (EVD) placement followed by new shunt insertion, or distal shunt externalization followed by new shunt insertion once the CSF is sterile. Antibiotic treatment includes the administration of intravenous antibiotics. The Hydrocephalus Clinical Research Network (HCRN) registry provides a unique opportunity to understand reinfection following treatment for CSF shunt infection. This study examines the association of surgical and antibiotic decisions in the treatment of first CSF shunt infection with reinfection. METHODS A prospective cohort study of children undergoing treatment for first CSF infection at 7 HCRN hospitals from April 2008 to December 2012 was performed. The HCRN consensus definition was used to define CSF shunt infection and reinfection. The key surgical predictor variable was surgical approach to treatment for CSF shunt infection, and the key antibiotic treatment predictor variable was intravenous antibiotic selection and duration. Cox proportional hazards models were constructed to address the time-varying nature of the characteristics associated with shunt surgeries. RESULTS Of 233 children in the HCRN registry with an initial CSF shunt infection during the study period, 38 patients (16%) developed reinfection over a median time of 44 days (interquartile range [IQR] 19-437). The majority of initial CSF shunt infections were treated with total shunt removal and EVD placement (175 patients; 75%). The median time between infection surgeries was 15 days (IQR 10-22). For the subset of 172 infections diagnosed by CSF culture, the mean ± SD duration of antibiotic treatment was 18.7 ± 12.8 days. In all Cox proportional hazards models, neither surgical approach to infection treatment nor overall intravenous antibiotic duration was independently associated with reinfection. The only treatment decision independently associated with decreased infection risk was the use of rifampin. While this finding did not achieve statistical significance, in all 5 Cox proportional hazards models both surgical approach (other than total shunt removal at initial CSF shunt infection) and nonventriculoperitoneal shunt location were consistently associated with a higher hazard of reinfection, while the use of ultrasound was consistently associated with a lower hazard of reinfection. CONCLUSIONS Neither surgical approach to treatment nor antibiotic duration was associated with reinfection risk. While these findings did not achieve statistical significance, surgical approach other than total removal at initial CSF shunt infection was consistently associated with a higher hazard of reinfection in this study and suggests the feasibility of controlling and standardizing the surgical approach (shunt removal with EVD placement). Considerably more variation and equipoise exists in the duration and selection of intravenous antibiotic treatment. Further consideration should be given to the use of rifampin in the treatment of CSF shunt infection. High-quality studies of the optimal duration of antibiotic treatment are critical to the creation of evidence-based guidelines for CSF shunt infection treatment.

Assessing a dual-frequency identification sonars' fish-counting accuracy, precision, and turbid river range capability.

Accurately assessing migrating salmon populations in turbid rivers with hydroacoustics is challenging. Using single, dual, or split-beam sonars, difficulties occur fitting acoustic beams between the river's narrow boundaries, distinguishing fish from nonfish echoes, and resolving individual fish at high densities. To address these issues, the fish-counting capability of a dual-frequency identification sonar (DIDSON), which produces high resolution, video-like images, was assessed. In a clear river, fish counts generated from a DIDSON, an echo counter, split-beam sonar, and video were compared to visual counts from a tower, a method frequently used to ground-truth sonars. The DIDSON and tower counts were very similar and showed the strongest agreement and least variability compared to the other methods. In a highly turbid river, the DIDSON's maximum detection range for a 10.16 cm spherical target was 17 m, less than absorption and wave spreading losses predict, and 26 m in clear water. Unlike tower and video methods, the DIDSON was not limited by surface disturbances or turbidity. DIDSON advantages over other sonars include: better target resolution; wider viewing angle; better coverage of the water column; accurate direction of travel; and simpler to aim and operate.

Opioid Analgesics Administered for Pain in the Inpatient Pediatric Setting.

This study aimed to describe utilization of opioid medications among infants, children, and adolescents on the inpatient setting. These data are needed to guide clinical trials and improve research methodologies, as well as to inform more about possible sources of opioid misuse in the United States. A retrospective chart review was conducted covering a span of 1 year, with a special focus on the prescription of opioids for long-term treatment of chronic pain. Opioid medications were prescribed for <5 days in most (75%) patients. Among those who were prescribed opioids for >14 days, the focus was often for reasons other than pain. These data indicate that models of chronic pain that may be utilized in clinical trials of longer-term opioid usage in pediatrics are exceedingly limited. In addition, the patterns of utilization indicate that opioid administration among pediatric inpatients is not a likely contributory factor to concerns about opioid misuse in the United States. PERSPECTIVE: This article presents data on the administration of opioids in a major children's hospital, with a special eye toward usage beyond treatment for short-term acute pain. These data are important to better inform discussions of research strategies for chronic pain, as well as concerns for misuse in the pediatric population.