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OBJECTIVES Unintended pregnancy in adolescents and young adults (AYAs) is linked with negative outcomes. We sought to evaluate the feasibility, acceptability, and preliminary efficacy of a contraception intervention in the pediatric hospital. METHODS We conducted a pilot study of hospitalized AYA females aged 14 to 21 years who reported past or anticipated sexual activity. A health educator offered a tablet-based intervention to provide contraception education and medications, if desired. We assessed feasibility (ie, intervention completion, duration, disruption to care), acceptability (ie, proportion rating as acceptable or satisfactory) among AYAs, parents or guardians, and healthcare providers, as well as preliminary efficacy (eg, contraception uptake) at enrollment and 3-month follow up. RESULTS We enrolled 25 AYA participants; mean age was 16.4 ± 1.5 years. The intervention demonstrated high feasibility as all enrolled participants (n = 25, 100%) completed the intervention and median intervention duration was 32 (interquartile range 25–45) minutes. Among 11 nurses, 82% (n = 9) reported the intervention was not at all or minimally disruptive to their workflow. All AYAs were very or somewhat satisfied with the intervention and 88% (n = 7) of 8 parents and guardians surveyed felt it was acceptable for the educator to meet privately with their child. Eleven participants (44%) started hormonal contraception, most commonly the subdermal implant (n = 7, 64%), and 23 (92%) received condoms. CONCLUSIONS Our findings support the feasibility and acceptability of our contraception intervention in the pediatric hospital resulting in contraception uptake among AYAs. Efforts to expand access to contraception are important to reduce unintended pregnancy, especially as restrictions to abortion are increasing in some states.

Background: Obesity in adolescents with intellectual and developmental disabilities) occurs at twice the frequency as their typically developing peers. Typically developing adolescents with obesity have abnormal cardiac function (as measured by strain echocardiography) and cardiac mass, but the effects of obesity on cardiac health in adolescents with Down syndrome or autism spectrum disorder are unknown. The purpose of this study was to evaluate the impact of body mass index on cardiac function in adolescents with Down syndrome or autism. Methods: Adolescents (age 12–21 years) with Down syndrome (n = 28), autism (n = 33), and age-/sex-matched typically developing controls (n = 15) received an echocardiogram optimised for strain analysis at a single timepoint. Measures of ventricular function, mass, and size were collected. Regression modelling evaluated the impact of body mass index and intellectual and developmental disabilities diagnosis on these cardiac measures. Results: In regression modelling, an elevated body mass index z-score was associated with diminished systolic biventricular function by global strain (left ventricular longitudinal strain β 0.87, P < 0.001; left ventricular circumferential strain β 0.57, p 0.003; right ventricular longitudinal strain β 0.63, P < 0.001). Diminished left ventricular diastolic function by early diastolic strain rate was also associated with elevated body mass index (global longitudinal end-diastolic strain rate β −0.7, P < 0.001). No association was found between traditional (non-strain) measures of systolic and diastolic ventricular function and body mass index z-score. Conclusions: Obesity in adolescents with Down syndrome or autism negatively impacts cardiac function as measured by echocardiographic strain analysis that was not detected by traditional parameters.

Background A better understanding of the extent to which psychosocial and environmental correlates of physical activity are specific to locations would inform intervention optimization. Purpose To investigate cross-sectional associations of location-general and location-specific variables with physical activity and sedentary time in three common locations adolescents spend time. Methods Adolescents (N = 472,Mage = 14.1,SD = 1.5) wore an accelerometer and global positioning systems (GPS) tracker and self-reported on psychosocial (e.g., self-efficacy) and environmental (e.g., equipment) factors relevant to physical activity and sedentary time. We categorized each survey item based on whether it was specific to a location to generate psychosocial and environmental indices that were location-general or specific to either school, non-school, or home location. Physical activity (MVPA) and sedentary time were based on time/location match to home, school, or all “other” locations. Mixed-effects models investigated the relation of each index with location-specific activity. Results The location-general and non-school physical activity psychosocial indices were related to greater MVPA at school and “other” locations. The school physical activity environment index was related to greater MVPA and less sedentary time at school. The home activity environment index was related to greater MVPA at home. The non-school sedentary psychosocial index was related to less sedentary time at home. Interactions among indices revealed adolescents with low support on one index benefited (i.e., exhibited more optimal behavior) from high support on another index (e.g., higher scores on the location-general PA psychosocial index moderated lower scores on the home PA environment index). Concurrent high support on two indices did not provide additional benefit. Conclusions No psychosocial or environment indices, including location-general indices, were related to activity in all locations. Most of the location-specific indices were associated with activity in the matching location(s). These findings provide preliminary evidence that psychosocial and environmental correlates of activity are location specific. Future studies should further develop location-specific measures and evaluate these constructs and whether interventions may be optimized by targeting location-specific psychosocial and environmental variables across multiple locations.

Objectives The aim of this study was to describe use of seclusion and restraint after injurious assaults by psychiatric inpatients in U.S. hospitals, including examination of hospital, unit, assaultive patient, and assault characteristics as predictors of seclusion/restraint use. Methods Data from 2004 to 2017 on 23,630 injurious assaults reported by 747 psychiatric units in 482 general hospitals were analyzed. Odds of seclusion, odds of three restraint types (device, hold, pharmacological), and duration of seclusion and device restraint were modeled as functions of hospital, unit, assaultive patient, and assault characteristics. Results Compared with teaching hospitals, nonteaching hospitals had lower rates of seclusion but higher rates of all three types of restraint. Seclusion and restraint rates were lower in government hospitals and hospitals in metropolitan settings. Pharmacological restraint was most common in for-profit hospitals; seclusion was most common in nonprofit hospitals. Episodes of seclusion and device restraint were approximately 20% shorter in teaching hospitals than in nonteaching hospitals and lasted markedly longer in federal government hospitals. Hospitals in metropolitan settings reported 30% longer time spent in seclusion, on average. Involuntary admission was associated with higher odds of seclusion, device restraint, and hold. Female patients were less likely than males to be restrained with a device, and their seclusion and device restraint episodes tended to be shorter. The number of persons injured in an assault predicted odds of seclusion and all three types of restraint. The maximum level of injury sustained predicted odds of seclusion, device restraint, and hold, as well as duration of both seclusion and device restraint. Odds of seclusion/restraint were lower when the most severely injured person was a patient rather than a clinical health care worker. Conclusions Inconsistencies were observed in seclusion and restraint use, which varied by hospital type, patient sex and admission status, maximum level of injury sustained, and type of person most severely injured. Thus, there may be room for improvement in hospital and unit policies and practices. More comprehensive data are needed for further research on use of seclusion and restraint in response to incidents other than injurious assault.

rs5758550 has been associated with enhanced transcription and suggested to be a useful marker of CYP2D6 activity. As there are limited and inconsistent data regarding the utility of this distant "enhancer" single nucleotide polymorphism (SNP), our goal was to further assess the impact of rs5758550 on CYP2D6 activity toward two probe substrates, atomoxetine (ATX) and dextromethorphan (DM), using in vivo urinary metabolite (DM; n = 188) and pharmacokinetic (ATX; n = 70) and in vitro metabolite formation (ATX and DM; n = 166) data. All subjects and tissues were extensively genotyped, the "enhancer" SNP phased with established CYP2D6 haplotypes either computationally or experimentally, and the impact on CYP2D6 activity investigated using several linear models of varying complexity to determine the proportion of variability in CYP2D6 activity captured by each model. For all datasets and models, the "enhancer" SNP had no or only a modest impact on CYP2D6 activity prediction. An increased effect, when present, was more pronounced for ATX than DM suggesting potential substate-dependency. In addition, CYP2D6*2 alleles with the "enhancer" SNP were associated with modestly higher metabolite formation rates in vitro, but not in vivo; no effect was detected for CYP2D6*1 alleles with "enhancer" SNP. In summary, it remains inconclusive whether the small effects detected in this investigation are indeed caused by the "enhancer" SNP or are rather due to its incomplete linkage with other variants within the gene. Taken together, there does not appear to be sufficient evidence to warrant the "enhancer" SNP be included in clinical CYP2D6 pharmacogenetic testing.

Introduction: Interventions targeting multiple levels of influence and settings may have a greater impact on children’s total daily physical activity than those targeting a single setting. This study evaluated the addition of family supports to a classroom-based physical activity intervention. Methods: 6 schools were randomized to a remotely delivered classroom-based physical activity only (CBPA) or classroom-based physical activity plus family (CBPA+) arm. The latter added behavior change tools (e.g., self-regulation) delivered via text messages and newsletters to caregiver/child dyads. The intervention lasted for 7 weeks with a 1-week baseline and 1-week post-intervention assessment (9 weeks total). Children who enrolled in the evaluation study received a Garmin activity monitor, which was used to tailor the text messages and evaluate changes in moderate to vigorous physical activity (MVPA). Caregivers completed surveys evaluating intervention acceptability. Results: The 53 child participants (CBPA n=35; CBPA+ n=18) were 9.7±0.7 years old, 64% were female, 59% were Black, and 23% were Hispanic/Latinx. Almost 90% of caregivers reported high satisfaction with the added family-based intervention content. Adherence to wearing the Garmin was higher in the CBPA+ arm. MVPA was low at baseline and during the first 3 weeks of the intervention (CBPA 7.5±3.1 minutes/day; CBPA+ 7.9±2.7 minutes/day) and increased by ~45 min/day by weeks 6-8 (CBPA 56.8±34.2 minutes/day; CBPA+ 49.2±18.7minutes/day). Changes in MVPA were similar between arms. Conclusion: The high acceptability and intervention engagement in the CBPA+ arm show promise for integrating mHealth tools to provide additional family support in multilevel multiapproach interventions targeting children’s physical activity.

Naltrexone, an opioid antagonist primarily metabolized by aldo-keto reductase 1C4 (AKR1C4), treats pediatric conditions involving compulsiveness (e.g., autism spectrum, Prader-Willi, eating disorders, non-suicidal self-injury). Pharmacokinetic variability is apparent in adults, yet no data are available for children. This study aimed to examine the impact of age and genetic variation on naltrexone biotransformation. Human liver cytosol (HLC) samples (n = 158) isolated from children and adult organ donors were incubated with therapeutically relevant concentrations of naltrexone (0.1, 1 µM). Naltrexone biotransformation was determined by ultraperformance mass spectrometry quantification of the primary metabolite, 6-beta-naltrexol (6βN), and 6βN formation rates (pmol/mg protein/min) were calculated. HLCs from organ donors, age range 0–79 y (mean 16.0 ± 18.2 y), 37% (n = 60) female, 20% (n = 33) heterozygous and 1.2% (n = 2) homozygous for co-occurring AKR1C4 variants (S145C/L311V) showed >200-fold range in 6βN formation (0.37–76.5 pmol/mg protein/min). Source of donor samples was found to be a substantial contributor to variability. Model estimates for a trimmed data set of source-adjusted pediatric samples (aged 0–18 y) suggested that AKR1C4 genetic variation, age, and sex explained 36% of the variability in 6βN formation. Although activity increased steadily from birth and peaked in middle childhood (2–5 years), genetic variation (S145C/L311V) demonstrated a greater effect on activity than did age. Naltrexone biotransformation is highly variable in pediatric and adult livers and can be partly accounted for by individual factors feasible to obtain (e.g., genetic variability, age, sex). These data may inform a precision therapeutics approach (e.g., exposure optimization) to further study Naltrexone responsiveness in children and adults. SIGNIFICANCE STATEMENT: Biotransformation of the commonly used opioid antagonist naltrexone is highly variable and may contribute to reduced therapeutic response. Age, sex, and genetic variation in the drug-metabolizing enzyme, AKR1C4, are potential factors contributing to this variability. In pediatric samples, genetic variation (S145C/L311V) demonstrates a greater impact on activity than age. Additionally, the source of donor samples was identified as an important contributor and must be accounted for to confidently elucidate the biological variables most impactful to drug biotransformation.

Microsomal protein per gram of liver (MPPGL) is an important scaling factor for bottom-up physiology-based pharmacokinetic modeling and simulation, but data in pediatrics are limited. Therefore, MPPGL was determined in 160 liver samples from pediatric (n = 129) and adult (n = 31) donors obtained from four sources: the University of Maryland Brain and Tissue Bank (UMBTB), tissue retrieval services at the University of Minnesota and University of Pittsburgh, and Sekisui-Xenotech. Tissues were homogenized and subjected to differential centrifugation to prepare microsomes, and cytochrome c reductase activities in tissue homogenates and microsomes were used to estimate cytochrome P450 reductase (POR) activity as a marker of microsomal recovery; microsomal POR content was also assessed by quantitative proteomics. MPPGL values varied 5- to 10-fold within various age groups/developmental stages, and tissue source was identified as a contributing factor. Using a “trimmed” dataset comprised of samples ranging from 3 to 18 years of age common to the four sources, POR protein abundance and activity in microsomes and POR activity in homogenates was lower in UMBTB samples (autopsy) compared with other sources (perfused/flash-frozen). Regression analyses revealed that the UMBTB samples were driving an apparent age effect as no effect of age on log-transformed MPPGL values was observed when the UMBTB samples were excluded. We conclude that a mean±SD MPPGL value of 30.4±1.7 mg/g is representative between one month postnatal age and early adulthood. Potential source effects should be considered for studies involving tissue samples from multiple sources with different procurement and processing procedures. SIGNIFICANCE STATEMENT: Microsomal protein per gram of liver (MPPGL) is an important scaling factor for bottom up PBPK modeling and simulation, but data in pediatrics are limited. Although MPPGL varies 5- to 10-fold at a given developmental stage, a value of 30.4 ± 1.7 mg/g (mean ± SD) is representative between one month postnatal age and early adulthood. However, when tissue samples are obtained from multiple sources, different procurement and processing procedures may influence the results and should be taken into consideration.

Clustered count data, common in health-related research, are routinely analyzed using generalized linear mixed models. There are two well-known challenges in small-sample inference in mixed modelin...

Objective Children with attention-deficit/hyperactivity disorder (ADHD) are at risk for accidental injuries, but little is known about age-related changes in early childhood. We predicted that ADHD would be associated with greater frequency and volume of accidental injuries. We explored associations between ADHD and injury types and examined age-related changes within the preschool period. Methods Retrospective chart review data of 21,520 preschool children with accidental injury visits within a large pediatric hospital network were examined. We compared children with ADHD (n = 524) and without ADHD (n = 20,996) on number of injury visits by age, total number of injury visits, injury volume, and injury type. Results Children with ADHD averaged fewer injury visits at age 3 and 90% more visits at age 6. Children with ADHD had injury visits in more years during the 3–6 age. There were no differences in injury volumes. Among patients with an injury visit at age 3, children with ADHD had 6 times the probability of a subsequent visit at age 6. At age 3, children with ADHD were estimated to have 50% fewer injury visits than children without ADHD, but by age 6, children with ADHD had an estimated 74% more injury visits than children without ADHD. Risk for several injury types for children with ADHD exceeded that for patients without ADHD by at least 50%. Conclusions Early identification and treatment of preschool ADHD following accidental injury may prevent subsequent injuries. Clinical implications and future directions are discussed with emphasis on the maintenance of parental monitoring into the older preschool years.

The goal of this study was to estimate the incidence of falls (total, injurious, and assisted) in U.S. psychiatric care across 6 years (April 2013-March 2019).Data on falls among patients of adult and geriatric psychiatric units of general, acute care, and psychiatric hospital inpatient units from the National Database of Nursing Quality Indicators were used for this 6-year study. Total falls, assisted falls (i.e., falls broken or slowed by staff), and injurious falls were calculated, along with trends in total and injurious fall rates.The sample included 1,159 units in 720 hospitals. Of the 119,246 falls reported, 25,807 (21.6%) resulted in injury. Only 7.0% of the total falls in psychiatric units were assisted by a staff member. Falling unassisted was associated with a higher likelihood of fall-related injury (adjusted odds ratio=1.69, 95% confidence interval=1.59 to 1.80). The total fall rate (8.55 per 1,000 patient-days) and injurious fall rate (1.97 per 1,000 patient-days) were highest for geriatric psychiatric units in general hospitals. Total and injurious fall rates in psychiatric units in general hospitals declined during the study (total fall rate declined by 10% for adult psychiatric units in general hospitals). There was no clear trend in total or injurious fall rates for units in psychiatric hospitals.Falls are a persistent problem in psychiatric care settings. Few fall-prevention programs have been tested in these settings, which have unique risk factors for falls. Additional research is needed to develop fall-prevention interventions in psychiatric care.

Objective:This study examined variability among U.S. hospitals in rates of seclusion and physical restraint, including the effects of hospital type and ownership, as reported on Hospital Compare. B...

Purpose Ewing Sarcoma Family of Tumors (ESFT), the second most common pediatric osseous malignancy, are characterized by the pathognomonic chromosomal EWS-ETS translocation. Outside of tumor biopsy, no clinically relevant ESFT biomarkers exist. Additionally, tumor burden assessment at diagnosis, monitoring of disease responsiveness to therapy, and detection of disease recurrence are limited to radiographic imaging. To identify new, clinically relevant biomarkers we evaluated the proteome of a subset of ESFT-derived small extracellular vesicles (sEVs). Materials and methods We performed the first high quality proteomic study of ESFT-derived sEVs from 5 ESFT cell lines representing the most common EWS-ETS fusion types and identified 619 proteins composing the core ESFT sEV proteome. We compared these core proteins to databases of common plasma-based proteins and sEV-associated proteins found within healthy plasma to identify proteins unique or enriched within ESFT. Results From these analyses, two membrane bound proteins with biomarker potential were selected, CD99/MIC2 and NGFR, to develop a liquid-based assay enriching of ESFT-associated sEVs and detection of sEV mRNA cargo (i.e., EWS-ETS transcripts). We employed this immuno-enrichment approach to diagnosis of ESFT utilizing plasma (250 μl) from both localized and metastatic ESFT pediatric patients and cancer-free controls, and showed significant diagnostic power [AUC = 0.92, p = 0.001 for sEV numeration, with a PPV = 1.00, 95% CI = (0.63, 1.00) and a NPV = 0.67, 95% CI = (0.30, 0.93)]. Conclusions In this study, we demonstrate utilization of circulating ESFT-associated sEVs in pediatric patients as a source of minimally invasive diagnostic and potentially prognostic biomarkers.

The ultrafiltrate flow over the major processes and cell body generates fluid flow shear stress (FFSS) on podocytes. Hyperfiltration-associated increase in FFSS can lead to podocyte injury and detachment. Previously, we showed that FFSS-induced upregulation of the cyclooxygenase 2 (COX2)-PGE2-prostaglandin E receptor 2 (EP2) axis in podocytes activates Akt-glycogen synthase kinase-3β-β-catenin and MAPK/ERK signaling in response to FFSS. Integrative MultiOmics Pathway Resolution (IMPRes) is a new bioinformatic tool that enables simultaneous time-series analysis of more than two groups to identify pathways and molecular connections. In the present study, we used previously characterized COX2 [prostaglandin-endoperoxide synthase 2 ( Ptgs2)], EP2 ( Ptger2), and β1-catenin ( Ctnnb1) as “seed genes” from an array data set of four groups analyzed over a time course. The 3 seed genes shared 7 pathways and 50 genes of 14 pathways and 89 genes identified by IMPRes. A composite of signaling pathways highlighted the temporal molecular connections during mechanotransduction signaling in FFSS-treated podocytes. We investigated the “proteoglycans in cancer” and “galactose metabolism” pathways predicted by IMPRes. A custom-designed PCR array validated 60.7% of the genes predicted by IMPRes analysis, including genes for the above-named pathways. Further validation using Western blot analysis showed increased expression of phosho-Erbb2, phospho-mammalian target of rapamycin (mTOR), CD44, and hexokinase II (Hk2); decreased total Erbb2, galactose mutarotase (Galm), and β-1,4-galactosyltransferase 1 (B4galt1); and unchanged total mTOR and AKT3. These findings corroborate our previously reported results. This study demonstrates the potential of the IMPRes method to identify novel pathways. Identifying the “proteoglycans in cancer” and “galactose metabolism” pathways has generated a lead to study the significance of FFSS-induced glycocalyx remodeling and possible detachment of podocytes from the glomerular matrix.

Objective Our study examines how consistently fall prevention practices and implementation strategies are used by U.S. hospitals. Methods We conducted a cross-sectional, descriptive study of 60 general adult hospital units.We administered a survey measuring 5 domains of fall prevention practices: visibility and identification, bed modification, patient monitoring, patient safety, and education. We measured 4 domains of implementation strategies including quality management (e.g., providing data and support for quality improvement), planning (e.g., designating leadership), education (e.g., providing consultation and training), and restructuring (e.g., revising staff roles and modifying equipment). Results Of 60 units, 43% were medical units and 57% were medical-surgical units. The hospital units varied in fall prevention practices, with practices such as keeping a patient's bed in a locked position (73% strongly agree) being used more consistently than other practices, such as scheduled toileting (15% strongly agree). Our study observed variation in fall prevention implementation strategies. For example, publicly posting fall rates (60% strongly agree) was more consistently used than having a multidisciplinary huddle after a fall event (12% strongly agree). Conclusions There is substantial variation in the implementation of fall prevention practices and implementation strategies across inpatient units. Our study found that resource-intensive practices (e.g., scheduled toileting) are less consistently used than less resource-intensive practices and that interdisciplinary approaches to fall prevention are limited. Future studies should examine how units tailor fall prevention practices based on patient risk factors and how units decide, based on their available resources, which implementation strategies should be used.

This study investigated the impact of SLCO1B1 genotype on rosuvastatin systemic exposure in hypercholesterolemic children and adolescents. Participants (8-21 years) with at least one allelic variant of SLCO1B1 c.521T>C (521TC, n = 13; 521CC, n = 2) and wild type controls (521TT, n = 13) completed a single oral dose pharmacokinetic study. The variability contributed by SLCO1B1 c.521 sequence variation to rosuvastatin (RVA) systemic exposure among our pediatric cohort was comparable to previous studies in adults. RVA concentration-time curve from 0-24 hours (AUC0-24 ) was 1.4-fold and 2.2-fold higher in participants with c.521TC and c.521CC genotype compared 521TT participants, respectively. Interindividual variability of RVA exposure within SLCO1B1 genotype groups exceeded the ~ 1.5-fold to 2-fold difference in mean RVA exposure observed among SLCO1B1 genotype groups, suggesting that other factors also contribute to interindividual variability in the rosuvastatin dose-exposure relationship. A multivariate model performed confirmed SLCO1B1 c.521T>C genotype as the primary factor contributing to RVA systemic exposure in this pediatric cohort, accounting for ~ 30% of the variability RVA AUC0-24 . However, of the statins investigated to date in the pediatric population, RVA has the lowest magnitude of variability in systemic exposure.

BackgroundTo guide fall prevention efforts, United States organisations, such as the Joint Commission and the Agency for Healthcare Research and Quality, have recommended organisational-level implementation strategies: leadership support, interdisciplinary falls committees, electronic health record tools, and staff, family and patient education. It is unclear whether hospitals adhere to such strategies or how these strategies are operationalised.ObjectiveTo identify and describe the prevalence of specific hospital fall prevention implementation strategies.MethodsIn 2017, we surveyed 80 US hospitals participating in the National Database of Nursing Quality Indicators who volunteered for the study. We conducted descriptive statistics by calculating percentages for categorical variables and the median and IQR for count variables.ResultsA total of 60/80 (75%) of hospitals completed the survey. The majority of hospitals were not-for-profit (98%) and urban (90%); more than half were Magnet (53%), small (53%) and teaching (52%). Hospitals were more likely to use leadership strategies, such as updating fall policies in the past 3 years (98%) but less likely to reward staff (40%). Hospitals commonly used interdisciplinary falls committees (83%) but membership rarely included physicians. Hospitals lacked access to electronic health record tools, such as high-risk medication warnings (27%). Education strategies were commonly used; 100% of hospitals provided fall education at staff orientation, but only 22% educated all employees (not just nursing staff).ConclusionsOur study is the first to our knowledge to examine which expert-recommended implementation strategies are being used and how they are being operationalised in US hospitals. Future studies are needed to document fall prevention implementation strategies in detail and to test which implementation strategies are most effective at reducing falls. Additionally, research is needed to evaluate the quality of implementation (eg, fidelity) of fall prevention interventions.

Purpose To test the validity of the Ecological Video Identification of Physical Activity (EVIP) computer vision algorithms for automated video-based ecological assessment of physical activity in settings such as parks and schoolyards. Methods Twenty-seven hours of video were collected from stationary overhead video cameras across 22 visits in nine sites capturing organized activities. Each person in the setting wore an accelerometer, and each second was classified as moderate-to-vigorous physical activity or sedentary/light activity. Data with 57,987 s were used to train and test computer vision algorithms for estimating the total number of people in the video and number of people active (in moderate-to-vigorous physical activity) each second. In the testing data set (38,658 s), video-based System for Observing Play and Recreation in Communities (SOPARC) observations were conducted every 5 min (130 observations). Concordance correlation coefficients (CCC) and mean absolute errors (MAE) assessed agreement between (1) EVIP and ground truth (people counts+accelerometry) and (2) SOPARC observation and ground truth. Site and scene-level correlates of error were investigated. Results Agreement between EVIP and ground truth was high for number of people in the scene (CCC = 0.88; MAE = 2.70) and moderate for number of people active (CCC = 0.55; MAE = 2.57). The EVIP error was uncorrelated with camera placement, presence of obstructions or shadows, and setting type. For both number in scene and number active, EVIP outperformed SOPARC observations in estimating ground truth values (CCC were larger by 0.11–0.12 and MAE smaller by 41%–48%). Conclusions Computer vision algorithms are promising for automated assessment of setting-based physical activity. Such tools would require less manpower than human observation, produce more and potentially more accurate data, and allow for ongoing monitoring and feedback to inform interventions.

Purpose:Dismissal of families who refuse mandated childhood vaccines from pediatric practices has become more common among US pediatricians over the past 2 decades. While nurses (registered nurses [RNs] and advanced practice registered nurses [APRNs]) often are the first health-care professional to encounter parents’ vaccine hesitancy and serve as a primary source of information, there are no published data on nurses’ perspectives on dismissal as a response to vaccine refusal. This study examined nurses’ perspectives on dismissal of vaccine-refusing families from primary care practices.Design:Cross-sectional survey administered electronically from February to September 2018. Data analysis was conducted from November 2018 to March 2019.Setting:Data were collected electronically from a national sample of nurses.Subjects:A convenience sample of 488 primary care nurses (74% APRNs) was recruited and enrolled in the study through collaboration with 4 professional nursing associations.Measure and Analysis:A cross-sectional survey was conducted from February to September 2018. We explored correlates of nurses’ (n = 488) attitudes toward dismissal by modeling attitude scores as a function of practice and respondent characteristics. We also modeled odds of encountering vaccine refusal and odds of reporting dismissal of a vaccine-refusing family in the last 12 months, each as a function of respondents’ practice characteristics.Results:Eighty-four percent of respondents encountered vaccine refusal in the previous 12 months, and 22% reported that their practice had dismissed a vaccine-refusing family within the previous 12 months. Twenty-eight percent agreed/strongly agreed that they would dismiss or support a decision to dismiss families who refuse all vaccines, and 12% supported dismissal of families for refusal of some but not all vaccines. Thirty-nine percent of respondents disagreed/strongly disagreed with dismissing families who refuse all vaccines, and 50% disagreed/strongly disagreed with dismissal for refusal of some but not all.Conclusion:Almost all nurses working in primary care encounter vaccine refusal, and most consider all Centers for Disease Control and Prevention–recommended childhood vaccines to be important to public health. There is significant polarization of nurses’ attitudes toward the appropriateness of dismissal as a response to vaccine refusal. We recommend the development of professional nursing guidelines for responding to vaccine refusal. However, because there are no data on the community health impact of dismissal policies, we recommend further research on outcomes of dismissal policies to inform such guidelines.

Objective Lumbar mobilization is a standard intervention for the management of low back pain, yet ways to quantify lumbar mobilization are limited. An inertial measurement unit (IMU) is a small and inexpensive device that can be used to quantify lumbar mobilization. The objective of this study was to determine the validity and reliability of an IMU in measuring the amplitude of displacement of a clinician's hand movement during oscillatory lumbar mobilization. Methods An IMU was secured on a clinician's hand during application of mobilization forces at the L4 segment of 16 healthy participants. The validity of the IMU was tested against common laboratory methods of measurements (force plate and motion capture system). The reliability of the IMU measurements was determined between 2 clinicians (inter-rater reliability) and between 2 sessions (intra-rater reliability) by calculating percent error of measurement (%e) and limits of agreement (LOA). The reliability was considered high when |%e| ≤ 10% and |LOA| ≤ 20%; moderate when |%e| 10% to 20% and |LOA| 21% to 40%; and non-acceptable when |%e| > 20% and |LOA| > 40%. Results The IMU measurements had high correlation with the force plate measurements (rs = 0.94) and high agreement with the motion capture system measurements (%e = 4%, LOA = -11% and 20%). Both the inter-rater reliability (%e = 6%, LOA = -25% and 37%) and the intrarater reliability (%e = -1%, LOA = -29% and 27%) of IMU measurements were moderate. Conclusion The IMU seems to be a valid device to measure the amplitude of a clinician's hand movement. The moderate reliability found in this study may not reflect poor reliability of the IMU as much as inconsistency in reapplication of lumbar mobilization.

Frailty is a multi-dimensional clinical syndrome that is associated with increased morbidity and mortality and decreased quality of life. Children/adolescents with heart disease (HD) perform significantly worse for each frailty domain compared to non-HD peers. Our study aimed to create a composite frailty score (CFS) that can be applied to children/adolescents with HD and evaluate associations between the CFS and outcomes. Children and adolescents (n = 30) with HD (73% single ventricle, 20% heart failure, 7% pulmonary hypertension) were recruited from 2016 to 2017 (baseline). Five frailty domains were assessed at baseline using measures validated for pediatrics: 1) Slowness: 6-minute walk test; 2) Weakness: handgrip strength; 3) Fatigue: PedsQL Multi-dimensional Fatigue Scale; 4) Body composition: triceps skinfold thickness; 5) Physical activity questionnaire. Frailty points per domain (range = 0–5) were assigned based on z-scores or raw questionnaire scores and summed to produce a CFS (0 = least frail; 25 = most frail). Nonparametric bootstrapping was used to identify correlations between CFS and cross-sectional change in outcomes over 2.2 ± 0.2 years. The mean CFS was 12.5 ± 3.5. In cross-sectional analyses of baseline data, correlations (|r|≥0.25) were observed between CFS and NYHA class, the number of ancillary specialists, total prescribed medications, heart failure medications/day, exercise test derived chronotropic index and percent predicted VO2peak, and between child and parent-proxy PEDsQL. At follow-up, CFS was correlated with an increase in the number of heart failure medications (r = 0.31). CFS was associated with cross-sectional outcomes in youth with heart disease. Longitudinal analyses were limited by small sample sizes due to loss to follow-up.

The

We examined diabetes status (no diabetes; type 1 diabetes [T1D]; type 2 diabetes [T2D]) and other demographic and clinical factors as correlates of coronavirus disease 2019 (COVID-19)-related hospitalization. Further, we evaluated predictors of COVID-19-related hospitalization in T1D and T2D.We analyzed electronic health record data from the de-identified COVID-19 database (December 2019 through mid-September 2020; 87 US health systems). Logistic mixed models were used to examine predictors of hospitalization at index encounters associated with confirmed SARS-CoV-2 infection.In 116,370 adults (=18 years old) with COVID-19 (93,098 no diabetes; 802 T1D; 22,470 T2D), factors that independently increased risk for hospitalization included diabetes, male sex, public health insurance, decreased body mass index (BMI;25.0-29.9 kg/mThe higher hospitalization risk in T1D versus T2D warrants further investigation. Modifiable risk factors such as vitamin D deficiency/insufficiency, BMI, and elevated HbA1c may serve as prognostic indicators for COVID-19-related hospitalization in adults with diabetes.

Patient reported outcomes are gaining more attention in patient-centered health outcomes research and quality of life studies as important indicators of clinical outcomes, especially for patients with chronic diseases. Factor analysis is ideal for measuring patient reported outcomes. If there is heterogeneity in the patient population and when sample size is small, differential item functioning and convergence issues are challenges for applying factor models. Bayesian hierarchical factor analysis can assess health disparity by assessing for di˙erential item functioning, while avoiding convergence problems. We conducted a simulation study and used an empirical example with American Indian minorities to show thatffitting a Bayesian hierarchical factor model is an optimal solution regardless of heterogeneity of population and sample size.

Early infant diagnosis (EID) involves age-specific tracking and testing of HIV-exposed infants during the first 18 months of life and rapid initiation of life-saving treatment for those infected. In Kenya, pre-2013 data estimate EID lost to follow-up (LTFU) at 39–65%, yet no study has documented LTFU rates and predictors throughout the EID cascade since Option B+ fundamentally changed services by placing all HIV-positive expectant mothers on lifelong treatment. Using an explanatory mixed-method design, we assessed LTFU rates and predictors among 870 mother–infant dyads enrolled in EID in six urban/peri-urban Kenyan government hospitals. Mothers completed baseline surveys, and dyads were tracked through EID. We selected 12 baseline variables and modeled odds of LTFU at 9 and 18 months using mixed logistic regression. Qualitative interviews were conducted with 61 mothers to assess barriers and facilitators to completing EID. Thematically coded transcripts were used to interpret quantitative predictors of LTFU. By the 18-month test, 145 dyads (22%) were LTFU, with three-quarters of LTFU occurring between 9- and 18-month tests. Odds of LTFU at 18 months decreased by 10% for each additional year of maternal age and by 66% with HIV status disclosure. Qualitative data revealed how disclosure facilitated essential social support for EID completion and how older mothers attributed maturity and life experience to successful engagement in care. Findings suggest LTFU rates in Kenya have declined, but gaps remain in ensuring universal coverage. Efforts to improve retention should focus on increasing support for younger mothers and those who have not disclosed their HIV status.

BACKGROUND Pediatric functional gastrointestinal disorders (FGIDs) are common and well-accepted to be etiologically complex in terms of the contribution of biological, psychological, and social factors to symptom presentations. Nonetheless, despite its documented benefits, interdisciplinary treatment, designed to address all of these factors, for pediatric FGIDs remains rare. The current study hypothesized that the majority of pediatric patients seen in an interdisciplinary abdominal pain clinic (APC) would demonstrate clinical resolution of symptoms during the study period and that specific psychosocial variables would be significantly predictive of GI symptom improvement. AIM To evaluate outcomes with interdisciplinary treatment in pediatric patients with pain-related FGIDs and identify patient characteristics that predicted clinical outcomes. METHODS Participants were 392 children, ages 8-18 [M = 13.8; standard deviation (SD) = 2.7], seen between August 1, 2013 and June 15, 2016 in an interdisciplinary APC housed within the Division of Gastroenterology in a medium-sized Midwestern children’s hospital. To be eligible, patients had to be 8 years of age or older and have had abdominal pain for ≥ 8 wk at the time of initial evaluation. Medical and psychosocial data collected as part of standard of care were retrospectively reviewed and analyzed in the context of the observational study. Logistic regression was used to model odds of reporting vs never reporting improvement, as well as to differentiate rapid from slower improvers. RESULTS Nearly 70% of patients followed during the study period achieved resolution on at least one of the employed outcome indices. Among those who achieved resolution during follow up, 43% to 49% did so by the first follow up (i.e., within roughly 2 mo after initial evaluation and initiation of interdisciplinary treatment). Patient age, sleep, ease of relaxation, and depression all significantly predicted the likelihood of resolution. More specifically, the odds of clinical resolution were 14% to 16% lower per additional year of patient age (P < 0.001 to P = 0.016). The odds of resolution were 28% to 42% lower per 1-standard deviation (SD) increase on a pediatric sleep measure (P = 0.006 to P < 0.040). Additionally, odds of clinical resolution were 58% lower per 1-SD increase on parent-reported measure of depression (P = 0.006), and doubled in cases where parents agreed that their children found it easy to relax (P = 0.045). Furthermore, sleep predicted the rapidity of clinical resolution; that is, the odds of achieving resolution by the first follow up visit were 47% to 60% lower per 1-SD increase on the pediatric sleep measure (P = 0.002). CONCLUSION Outcomes for youth with FGIDs may be significantly improved by paying specific attention to sleep, ensuring adequate skills for relaxation, and screening of and referral for treatment of comorbid depression.

Ewing sarcoma (ES) are aggressive pediatric bone and soft tissue tumors driven by EWS-ETS fusion oncogenes, most commonly EWS-FLI1. Treatment of ES patients consists of up to 9 months of alternating courses of 2 chemotherapeutic regimens. Furthermore, EWS-ETS-targeted therapies have yet to demonstrate clinical benefit, thereby emphasizing a clinical responsibility to search for new therapeutic approaches. Our previous in silico drug screening identified entinostat as a drug hit that was predicted to reverse the ES disease signatures and EWS-FLI1-mediated gene signatures. Here, we establish preclinical proof of principle by investigating the in vitro and in vivo efficacy of entinostat in preclinical ES models, as well as characterizing the mechanisms of action and in vivo pharmacokinetics of entinostat. ES cells are preferentially sensitive to entinostat in an EWS-FLI1 or EWS-ERG-dependent manner. Entinostat induces apoptosis of ES cells through G0/G1 cell cycle arrest, intracellular reactive oxygen species (ROS) elevation, DNA damage, homologous recombination (HR) repair impairment, and caspase activation. Mechanistically, we demonstrate for the first time that HDAC3 is a transcriptional target of EWS-FLI1 and that entinostat inhibits growth of ES cells through suppressing a previously unexplored EWS-FLI1/HDAC3/HSP90 signaling axis. Importantly, entinostat significantly reduces tumor burden by 97.4% (89.5 vs. 3397.3 mm3 of vehicle, p

BACKGROUND Hepatic sinusoidal obstruction syndrome (SOS) is a potentially fatal complication after hematopoietic stem cell transplantation (HSCT). Current clinical guidelines state that spectral Doppler changes occur late in the disease, and imaging is only useful for confirming SOS diagnosis. OBJECTIVE Our primary objective was to examine abdominal ultrasound variables as predictors of development of SOS in pediatric HSCT patients. MATERIALS AND METHODS A single-center cohort retrospective study was conducted on patients aged 0 to 21 years who underwent HSCT between September 2001 and May 2017 at our institution. Patients were excluded if they did not have abdominal ultrasounds after HSCT. Clinical, demographic, grayscale, and spectral Doppler liver ultrasound findings were evaluated. We modeled the odds of SOS diagnosis within 100 days after HSCT as a function of each of the 15 ultrasound variables. RESULTS A total of 333 patients received an HSCT. One hundred forty subjects had ultrasound data available. Thirty-two patients developed SOS, and 9 of these patients died. Sinusoidal obstruction syndrome odds more than double per 1-SD increase in peak systolic velocity in common hepatic artery or left hepatic artery and more than triple per 1-SD decrease in main portal vein velocity or change in ascites severity. Several ultrasound variables were statistically significant predictors in the Cox models for time to SOS diagnosis. CONCLUSION Several ultrasound variables can be used as predictors for a patient's risk of developing SOS. The strongest predictors are ascites severity, main portal vein velocity, common hepatic artery peak systolic velocity, and left hepatic artery peak systolic velocity.

Ductal carcinoma in situ (DCIS) is the most common type of pre-invasive breast cancer diagnosed in women. Because the majority of DCIS cases are unlikely to progress to invasive breast cancer, many women are over-treated for DCIS. By understanding the molecular basis of early stage breast cancer progression, we may identify better prognostic factors and design treatments tailored specifically to the predicted outcome of DCIS. Chemokines are small soluble molecules with complex roles in inflammation and cancer progression. Previously, we demonstrated that CCL2/CCR2 chemokine signaling in breast cancer cell lines regulated growth and invasion through p42/44MAPK and SMAD3 dependent mechanisms. Here, we sought to determine the clinical and functional relevance of CCL2/CCR2 signaling proteins to DCIS progression. Through immunostaining analysis of DCIS and IDC tissues, we show that expression of CCL2, CCR2, phospho-SMAD3 and phospho-p42/44MAPK correlate with IDC. Using PDX models and an immortalized hDCIS.01 breast epithelial cell line, we show that breast epithelial cells with high CCR2 and high CCL2 levels form invasive breast lesions that express phospho-SMAD3 and phospho-p42/44MAPK. These studies demonstrate that increased CCL2/CCR2 signaling in breast tissues is associated with DCIS progression, and could be a signature to predict the likelihood of DCIS progression to IDC.

Background Safer conception counseling (SCC) to promote the use of safer conception methods (SCM) is not yet part of routine family planning or HIV care. Guidelines for the use of SCM have been published, but to date there are no published controlled evaluations of SCC. Furthermore, it is unknown whether standard methods commonly used in resource constrained settings to integrate new services would be sufficient, or if enhanced training and supervision would result in a more efficacious approach to implementing SCC. Methods In a hybrid, cluster randomized controlled trial, six HIV clinics were randomly assigned to implement the SCC intervention Our Choice using either a high (SCC1) or low intensity (SCC2) approach (differentiated by amount of training and supervision), or existing family planning services (usual care). Three hundred eighty-nine HIV clients considering childbearing with an HIV-negative partner enrolled. The primary outcome was self-reported use of appropriate reproductive method (SCM if trying to conceive; modern contraceptives if not) over 12 months or until pregnancy. Results The combined intervention groups used appropriate reproductive methods more than usual care [20.8% vs. 6.9%; adjusted OR (95% CI)=10.63 (2.79, 40.49)], and SCC1 reported a higher rate than SCC2 [27.1% vs. 14.6%; OR (95% CI)=4.50 (1.44, 14.01)]. Among those trying to conceive, the intervention arms reported greater accurate use of SCM compared to usual care [24.1% vs. 0%; OR (95% CI)=91.84 (4.94, 1709.0)], and SCC1 performed better than SCC2 [34.6% vs. 11.5%; OR (95% CI)=6.43 (1.90, 21.73)]. The arms did not vary on modern contraception use among those not trying to conceive. A cost of $631 per person was estimated to obtain accurate use of SCM in SCC1, compared to $1014 in SCC2. Conclusions More intensive provider training and more frequent supervision leads to greater adoption of complex SCM behaviors and is more cost-effective than the standard low intensity implementation approach. Trial registration Clinicaltrials.gov, NCT03167879; date registered May 23, 2017.

In the above article the abstract incorrectly states, “International rates of mechanical restraint in 2017 varied from 0.03 (New Zealand) to 98.9 (Japan) restraint events per million population per day”. The rate in Japan has been corrected to 98.8 as is found in the text of the article.

Aims The use of mechanical restraint is a challenging area for psychiatry. Although mechanical restraint remains accepted as standard practice in some regions, there are ethical, legal and medical reasons to minimise or abolish its use. These concerns have intensified following the Convention on the Rights of Persons with Disabilities. Despite national policies to reduce use, the reporting of mechanical restraint has been poor, hampering a reasonable understanding of the epidemiology of restraint. This paper aims to develop a consistent measure of mechanical restraint and compare the measure within and across countries in the Pacific Rim. Methods We used the publicly available data from four Pacific Rim countries (Australia, New Zealand, Japan and the United States) to compare and contrast the reported rates of mechanical restraint. Summary measures were computed so as to enable international comparisons. Variation within each jurisdiction was also analysed. Results International rates of mechanical restraint in 2017 varied from 0.03 (New Zealand) to 98.8 (Japan) restraint events per million population per day, a variation greater than 3000-fold. Restraint in Australia (0.17 events per million) and the United States (0.37 events per million) fell between these two extremes. Variation as measured by restraint events per 1000 bed-days was less extreme but still substantial. Within all four countries there was also significant variation in restraint across districts. Variation across time did not show a steady reduction in restraint in any country during the period for which data were available (starting from 2003 at the earliest). Conclusions Policies to reduce or abolish mechanical restraint do not appear to be effecting change. It is improbable that the variation in restraint within the four examined Pacific Rim countries is accountable for by psychopathology. Greater efforts at reporting, monitoring and carrying out interventions to achieve the stated aim of reducing restraint are urgently needed.