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Objectives: To determine the impact of physical activity on temperature after within-limb calibration (TAWiC) measures and their reproducibility. To determine if thermal imaging from a smartphone attached thermal camera is comparable to thermal imaging using a handheld thermal camera for detection of arthritis in children., Methods: Children without symptoms were enrolled to the "asymptomatic exercise cohort", and received infrared imaging, using a standard handheld camera, after initial resting period, after activity, and after second resting period. Children seen in the rheumatology clinic with knee pain were enrolled into the "symptomatic knee pain cohort" and received imaging with both the smartphone-attached and handheld cameras before a routine clinical exam. TAWiC was defined as the temperature differences between joint and ipsilateral mid-tibia as the main readout for arthritis detection., Results: The asymptomatic exercise cohort demonstrated notable changes in absolute and TAWiC temperatures collected by thermal imaging after physical activity, and temperatures did not consistently return to pre-activity levels after a second period of rest. The 95th TAWiC from anterior view were, resting one -0.1 C (0.5), activity -0.7 C (0.5), resting two -0.2 C (0.6) (resting 1 vs resting 2, p-value = 0.13). In the symptomatic knee pain cohort, the smartphone attached and handheld thermal cameras performed similarly in regards to detection of joint inflammation and evaluation of joint temperature using the TAWiC algorithm, with high sensitivity of 80% (55.2-100.0%) and specificity of 84.2% (76.0-92.4%) in the anterior knee view when compared with the gold standard joint exam performed by a pediatric rheumatologist. The mean 95th TAWiC temperature difference between the two cameras was -0.1 C (-0.1 to 0.0) (p = 0.0004)., Conclusions: This study showed continued validity of the TAWiC algorithm across two distinct thermal camera platforms and demonstrates promise for improved accessibility and utility of this technology for arthritis detection., 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 Elsevier Ltd. All rights reserved.)

Objective: While previous studies have described psychiatric profiles in patients with psychogenic non-epileptic seizures (PNES) and epileptic seizures (ES), a well-matched comparison between males and females has been lacking. To address this shortcoming, the present study sought to explore sex differences between male and female Veterans with ES and PNES in terms of psychiatric diagnoses, trauma histories, and psychiatric treatment., Methods: A male Veteran sample (PNES n = 87, ES n = 28) was identified matching age and seizure diagnosis with our previously-gathered female Veteran sample (PNES n = 90, ES n = 28). Retrospective chart review was used to obtain demographic, psychiatric, and seizure-related variables. Group differences between PNES and ES were first assessed among males followed by differences between males and females., Results: Males with PNES were more likely to receive psychiatric treatment (82.6 % vs. 60.7 %, p = 0.017), be prescribed more psychotropics (1.6 vs. 0.9, p = 0.003), and more likely to have childhood physical abuse (27.9 % vs. 3.6 %, p = 0.007) than those with ES. Compared to PNES, males with ES presented to the epilepsy monitoring unit (EMU) significantly later (12.8 years vs. 6.1 years, p = 0.009), and were prescribed more anti-seizure medications (ASMs) previously (2.1 vs. 0.8, p = 0.009) and currently (1.6 vs. 1.0, p = 0.001). Between males and females with PNES, females evidenced more depression (76.7 % vs. 26.3 %, p < 0.001), borderline personality disorder (18.9 % vs. 4.7 %, p = 0.004), suicidality (65.6 % vs. 33.7 %, p < 0.001), and childhood sexual abuse (37.8 % vs. 11.6 %, p < 0.001), while males had higher rates of substance use disorders (37.2 % vs. 8.9 %, p < 0.001)., Significance: A greater psychiatric burden is seen among females compared to males with PNES, especially diagnoses of borderline personality disorder and depression. Higher rates of suicidality and inpatient psychiatric hospitalization may warrant particular consideration in screening and intervention efforts among female Veterans with PNES., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: Only 4% of brief resolved unexplained events (BRUE) are caused by a serious underlying illness. The American Academy of Pediatrics (AAP) guidelines do not distinguish patients who would benefit from further investigation and hospitalization. We aimed to derive and validate a clinical decision rule for predicting the risk of a serious underlying diagnosis or event recurrence., Methods: We retrospectively identified infants presenting with a BRUE to 15 children's hospitals (2015-2020). We used logistic regression in a split-sample to derive and validate a risk prediction model., Results: Of 3283 eligible patients, 565 (17.2%) had a serious underlying diagnosis (n = 150) or a recurrent event (n = 469). The AAP's higher-risk criteria were met in 91.5% (n = 3005) and predicted a serious diagnosis with 95.3% sensitivity, 8.6% specificity, and an area under the curve of 0.52 (95% confidence interval [CI]: 0.47-0.57). A derived model based on age, previous events, and abnormal medical history demonstrated an area under the curve of 0.64 (95%CI: 0.59-0.70). In contrast to the AAP criteria, patients >60 days were more likely to have a serious underlying diagnosis (odds ratio:1.43, 95%CI: 1.03-1.98, P = .03)., Conclusions: Most infants presenting with a BRUE do not have a serious underlying pathology requiring prompt diagnosis. We derived 2 models to predict the risk of a serious diagnosis and event recurrence. A decision support tool based on this model may aid clinicians and caregivers in the discussion on the benefit of diagnostic testing and hospitalization (https://www.mdcalc.com/calc/10400/brief-resolved-unexplained-events-2.0-brue-2.0-criteria-infants)., (Copyright © 2022 by the American Academy of Pediatrics.)

Advanced systemic mastocytosis (AdvSM) is a rare myeloid neoplasm associated with poor overall survival (OS). This study (NCT04695431) compared clinical outcomes between patients with AdvSM treated with avapritinib in the Phase 1 EXPLORER (NCT0256198) and Phase 2 PATHFINDER (NCT03580655) trials (N = 176) and patients treated with best available therapy (BAT; N = 141). A multi-center, observational, retrospective chart review study was conducted at six study sites (four European, two American) to collect data from patients with AdvSM who received BAT; these data were pooled with data from EXPLORER and PATHFINDER. Comparisons between outcomes of OS, duration of treatment (DOT), and maximum reduction in serum tryptase were conducted between the treatment cohorts, with adjustment for key covariates. The results indicated that the avapritinib cohort had significantly better survival (adjusted hazard ratio (HR) (95% confidence interval (CI)): 0.48 (0.29, 0.79); p = 0.004) and significantly longer DOT (HR: 0.36 (0.26, 0.51); p < 0.001) compared to the BAT cohort. Additionally, the mean difference in percentage maximum reduction in serum tryptase levels was 60.3% greater in the avapritinib cohort (95% CI: -72.8, -47.9; p < 0.001). With no randomized controlled trials comparing avapritinib to BAT, these data offer crucial insights into the improved efficacy of avapritinib for the treatment of AdvSM., (© 2022. The Author(s).)

Introduction: School-based health centers (SBHCs) provide health services to more than six million youth annually. When schools throughout the United States closed in spring 2020, many SBHCs were also forced to close physical operations.., Method: This study uses qualitative data collected from SBHC representatives nationwide to examine supports and challenges affecting mental health services provision during the COVID-19 pandemic, changes in the provision of these services, and priorities for assessing and supporting student mental health needs in the 2021-2022 school year., Results: Partnerships, community and stakeholder buy-in, and student access were key supports to continuous care throughout the pandemic, whereas lack of available staff and lack of in-person access to students were key challenges. Patients demonstrated increased acuity of presenting mental health problems, more immediate and complex mental health challenges, and greater co-morbidities., Discussion: SBHCs pivoted, even with limited resources, to meet students' increasing needs for mental health care., (Copyright © 2022. Published by Elsevier Inc.)

Introduction: While women now represent a majority of neuropsychology trainees, men remain prominent in senior positions. As such, female mentees are often paired with senior male mentors, a practice referred to as "cross-gender mentorship." Although cross-gender mentoring dynamics have inherent potential for missteps due to implicit power differentials, when approached through a gender-informed lens, they can be optimized and lead to personal and professional growth for women neuropsychologists. The present article provides a framework for promoting gender-informed mentorship by cataloging first-hand accounts of early career women and discussing resultant lessons and concrete suggestions for mentorship., Method: The authors provide first-hand accounts of experiences related to cross-gender mentorship across a variety of settings and professional contexts. From these accounts, the following steps offer a framework to encourage effective mentorship: 1) Set appropriate expectations and boundaries, 2) Address challenging clinical interactions through a gender-informed lens, 3) Foster personal and professional development, 4) Understand the intersection between gender and multicultural traits, 5) Advocate for advancement of women in the field, and 6) Maintain knowledge of women's issues., Conclusions: Providing effective mentorship for women in neuropsychology is crucial to promote ascension of women to leadership positions and close long-established disparities in the field. The authors hope that our shared experiences can serve as useful tools for both women trainees and their mentors as they embark on mentoring relationships. Practically, we envision that mentoring dyads may discuss this article at the outset of their relationship to understand potential challenges and collaboratively establish a groundwork for optimal mentoring.

Objective: We aimed to investigate the relationship between tumour necrosis factor inhibitors (TNFi) therapy and the onset of new psoriasis in children with juvenile idiopathic arthritis (JIA) using Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry data., Methods: De-identified data were obtained from the CARRA Registry. Patients with inflammatory bowel disease or psoriasis documented on or prior to JIA diagnosis date or with incomplete data were excluded. Exposure to TNFi was categorised as: (1) ever use; (2) current use or (3) first use only. Adjusted HRs (aHRs) were calculated between exposed and unexposed groups adjusted for methotrexate exposure, sex, race, family history of psoriasis and initial JIA category., Results: A total of 8225 patients were included with a median follow-up of 3.9 years. Over half of the patients were prescribed TNFi (n=4437, 54%). The aHR of new onset of psoriasis after ever exposure to TNFi was 2.93 (2.15 to 3.98). The incidence rate of psoriasis was the highest in children ever receiving and actively receiving adalimumab. Ever concurrent methotrexate use (HR 0.45, 0.29 to 0.69) was associated with lower risk., Conclusion: In a large prospective JIA patient registry, we observed a nearly threefold increased risk of psoriasis after TNFi exposureCite Now., Competing Interests: Competing interests: YZ receives research funding from Childhood Arthritis and Rheumatology Research Alliance (CARRA), ACR/EULAR, Bristol-Myers Squibb and Washington Research Foundation and consultant fees from Novartis. MBS receives funding from CARRA, the Centers for Disease Control and Disease Prevention, PCORI and the Samara Jan Turkel Clinical Center for Autoimmune Disease. TB receives funding from CARRA and consultant fees from UCB and Novartis., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Over the past several decades, there have been advances in diagnosis and treatment of neonatal herpes simplex virus (HSV) disease. There has been no recent comprehensive evaluation of the impact of these advances on the management and outcomes for neonates with HSV., Methods: Clinical data for initial presentation, treatment, and outcomes were abstracted from medical records of neonates with HSV treated at Seattle Children's Hospital between 1980 and 2016., Results: One hundred thirty infants with a diagnosis of neonatal HSV were identified. Between 1980 and 2016, high-dose acyclovir treatment for neonatal HSV infection increased from 0% to close to 95%, with subsequent decrease in overall HSV-related mortality from 20.9% to 5.6%. However, even among infants treated with high-dose acyclovir, mortality was 40.9% for infants with disseminated (DIS) disease, and only 55% of infants with central nervous system (CNS) disease were without obvious neurologic abnormalities at 24 months. Over the study period, the time between initial symptoms and diagnosis decreased. Skin recurrences were more common with HSV-2 than HSV-1 (80% vs 55%; P = .02) and in infants with lesions at initial diagnosis (76% vs 47%; P = .02)., Conclusion: Changes in the standard of care for management of neonatal HSV disease have led to improvements in timeliness of diagnosis and outcome but mortality in infants with DIS disease and neurologic morbidity in infants with CNS disease remain high. Future research should focus on prevention of perinatal infection and subsequent recurrences., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Bacillus cereus group isolates ( n  = 85) were screened for phenotypic resistance to 18 antibiotics using broth microdilution and CLSI M45 Bacillus spp. breakpoints. The susceptibility to 9 out of 18 antibiotics was also tested using disk diffusion method and M100 Staphylococcus spp. breakpoints when available. Overall, a high prevalence of susceptibility to clinically relevant antibiotics was identified using broth microdilution. For most tested antibiotics, a poor correlation was found between zones of inhibition and MICs. Using the broth microdilution results as a reference for comparison, we identified high error rates and low categorical agreement between results produced using disk diffusion and broth microdilution for the seven tested antibiotics with defined breakpoints. This suggests that disk diffusion should be avoided for AST of B. cereus group isolates. Further, we detected antimicrobial resistance genes with ARIBA and ABRIcate to calculate the sensitivity and specificity for predicting phenotypic resistance determined using broth microdilution based on the presence of detected antimicrobial resistance genes (ARGs). ARGs with poor sensitivity and high specificity included rph (rifampicin, 0%, 93%), mph (erythromycin, 0%, 99%), bla1 (penicillin, 29%, 100%), and blaZ (penicillin, 56%, 100%). Compared to penicillin, bla1 and blaZ had lower specificity for the prediction of ampicillin resistance. Overall, none of the ARGs had both high sensitivity and specificity, suggesting the need for further study of the mechanisms underlying phenotypic antimicrobial resistance in the B. cereus group. IMPORTANCE Bacillus cereus group includes human pathogens that can cause severe infections requiring antibiotic treatment. Screening of environmental and food isolates for antimicrobial resistance can provide insight into what antibiotics may be more effective therapeutic options based on the lower prevalence of resistance. Currently, the comparison of antimicrobial susceptibility testing results using the disk diffusion method is complicated by the fact that many previous studies have used Staphylococcus spp. breakpoints to interpret their results. In this study, we compared the results of disk diffusion interpreted using the Staphylococcus spp. breakpoints against the results of broth microdilution interpreted using Bacillus spp. breakpoints. We demonstrated that the disk diffusion method does not produce reliable results for B. cereus group isolates and should therefore be avoided. This study also provides new insight into poor associations between the presence of antimicrobial resistance genes and resistance phenotypes for the B. cereus group.

Objective: Health literacy is a strong psychosocial determinant of health disparities and has been found to relate to various aspects of health-related technology use. With the increased implementation of neuropsychological services performed via telehealth during the coronavirus disease 2019 pandemic, the relationship between health literacy and comfort with teleneuropsychology warrants further investigation., Method: The present study examined 77 Veterans participating in neuropsychological evaluations as a part of standard clinical care. The sample was diverse in terms of age ethnicity, and psychiatric and neurocognitive diagnoses. In addition to a fixed-flexible neuropsychological battery, the Brief Health Literacy Screening Tool (BRIEF) was administered to evaluate health literacy. Self-reported comfort with the teleneuropsychological evaluation was assessed using an informal 10-point scale, and qualitative comfort responses were also recorded., Results: Independent samples t-tests revealed older adults were more likely to participate in the evaluation via telephone than with VA Video Connect. Although health literacy was not related to telehealth modality, it was correlated with comfort with the teleneuropsychological evaluation (r = .34, p < .01), although it is notable that average comfort levels were high across modalities (M = 8.16, SD = 2.50)., Conclusions: Findings support the notion that teleneuropsychological services may feasibly be implemented with a diverse group of patients, although flexibility with modality may be necessary. Those performing these services should also be aware that patients with lower health literacy may feel less comfortable with teleneuropsychology as they seek to build rapport and optimize evaluation engagement., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

There is a growing appreciation for differences in epidemiology, treatment, and outcomes of cardiovascular conditions by sex. Historically, cardiovascular clinical trials have under-represented females, but findings have nonetheless been applied to clinical care in a sex-agnostic manner. Thus, much of the collective knowledge about sex-specific cardiovascular outcomes result from post hoc and secondary analyses. In some cases, these investigations have revealed important sex-based differences with implications for optimizing care for female patients with arrhythmias. This review explores the available evidence related to cardiac arrhythmia care among females, with emphasis on areas in which important sex differences are known or suggested. Considerations related to improving female enrollment in clinical trials as a way to establish more robust clinical evidence for the treatment of females are discussed. Areas of remaining evidence gaps are provided, and recommendations for areas of future research and specific action items are suggested. The overarching goal is to improve appreciation for sex-based differences in cardiac arrhythmia care as 1 component of a comprehensive plan to optimize arrhythmia care for all patients.

Objective: The number and proportion of women served by the Veterans Health Administration (VHA) is rapidly expanding, necessitating better characterization of factors unique to this population. While nascent literature has begun to better characterize women within the broader seizure population, women Veterans remain an understudied sample. To expand our clinical understanding of women with seizures, we assessed demographic and clinical characteristics, as well as psychiatric/military histories in women receiving care from an Epilepsy Center of Excellence within the VA Healthcare System., Methods: The sample included 90 women with psychogenic nonepileptic seizures (PNES) and 28 women with epileptic seizures (ES) as the final diagnosis after epilepsy monitoring at a large VA medical center between 2010 and 2020. Retrospective chart review gathered demographics, including age, marital status, and work status; clinical characteristics, including history of traumatic brain injury (TBI) or migraines, gynecological history, and use of anti-seizure medications (ASM); psychiatric information, including trauma history, psychiatric diagnoses, and treatment; and military history related to service or service connection. Group differences were assessed between women with PNES and ES., Results: The ES group was significantly older than the PNES group (47.8 v. 41.9 years, p = 0.02) and had a non-significantly longer diagnosis duration (12.3 vs. 8.6 years, p = 0.17). Clinically, the PNES group had a significantly higher rate of migraines (76.7% v. 57.1%, p = 0.04) and hysterectomy (40% v. 17.9%, p = 0.03). Many psychiatric factors differentiated the two groups, with significantly higher rates of psychotropic medication use (86.7% v. 60.7%, p = 0.002), psychiatric hospitalization (42.2% v. 21.4%, p = 0.047), and suicide attempts (42.2% v. 14.3%, p = 0.005), alongside trends toward higher rates of military sexual trauma (47.8% vs. 28.6%, p = 0.07) and childhood sexual trauma (37.8% vs. 17.9%, p = 0.05) among those with PNES., Significance: This is the largest study to date characterizing women veterans with seizures seeking comprehensive seizure care and provides an update to previously published information on Veteran samples with seizures. Several characteristics differ between women Veterans with PNES and ES, spanning demographic, clinical, and psychiatric factors. Understanding the unique profile of women Veterans with epilepsy seeking care through the VA system is a crucial step in providing optimal care, including making informed diagnosis and providing appropriate treatment., (Copyright © 2022 Elsevier B.V. All rights reserved.)

BACKGROUND: Lung cancer is the leading cause of cancer death in the United States. Non-small cell lung cancer (NSCLC) accounts for 80% to 85% of all lung cancers. Thyroid cancer, while generally not as lethal as lung cancer, has a large prevalent population and a rapidly increasing incidence in the United States. Pralsetinib is a highly potent, selective rearranged during transfection ( RET ) inhibitor indicated for the treatment of RET -positive NSCLC and thyroid cancer tumors. OBJECTIVE: To estimate the budget impact of adding pralsetinib to a 1 million-member US health plan formulary for the treatment of patients with metastatic RET fusion-positive NSCLC, advanced or metastatic RET -mutant medullary thyroid cancer (MTC), or advanced or metastatic RET fusion-positive thyroid cancer (non-MTC). METHODS: A budget impact model with a 3-year time horizon was developed in Microsoft Excel to estimate the number of eligible RET -positive NSCLC and thyroid cancer patients in a plan and quantify associated treatment costs (2020 USD). Comparators in the analyses included pralsetinib, selpercatinib, and cabozantinib, as well as indication-specific use of pembrolizumab, pemetrexed/carboplatin combination, vandetanib, lenvatinib, and sorafenib. Drug acquisition, molecular testing, treatment monitoring, and adverse event management costs were included to estimate total annual costs and per-member per-month (PMPM) costs in current (without pralsetinib) and potential future market scenarios, where pralsetinib is assumed to split the projected RET inhibitor market share with selpercatinib. The number of treated patients was based on age- and sex-adjusted incidence of disease, the proportion of patients diagnosed with advanced or metastatic disease, and projected RET testing rates. Treatment duration was based on progression-free survival or duration of response data from clinical trials. Medical resources were monetized using standardized sources such as Medicare reimbursement and wholesale acquisition cost (WAC). RESULTS: The model estimated that there would be approximately 6 new treatment-eligible patients in a 1 million-member plan annually. Monthly WAC is $19,243 for pralsetinib and $20,600 for selpercatinib at the recommended starting dose. Adoption of pralsetinib, with corresponding increases in pralsetinib market share, would be slightly cost saving to a payer, decreasing the overall budget impact to the health plan by $49,985 in year 3 (-$0.0042 PMPM; -$0.0030, -$0.0006, and -$0.0005 for NSCLC, MTC, and thyroid cancer [non-MTC], respectively). In year 3, drug costs were the key driver of total costs (~80%-98%) and cost savings. All other medical resource categories were cost-neutral or nominally cost saving or additive in the budget impact analysis. CONCLUSIONS: Quantifying the budget impact associated with the adoption of new targeted precision therapies is an important consideration for payers. For eligible NSCLC and thyroid cancer patients, our analysis suggests that adoption of pralsetinib is expected to result in modest cost savings for US payers. DISCLOSURES: Support for this study was provided by Blueprint Medicines Corporation. This study was conducted by Veritas Health Economics Consulting, Inc., in collaboration with Blueprint Medicines, which was involved in the design of the study; collection, analysis, and interpretation of the data; writing of the report; and the decision to submit the report for publication. Duff is an employee of Veritas Health Economics Consulting, which received research funding from Blueprint Medicines to develop the budget impact model. Norregaard and Sullivan are employees of Blueprint Medicines. Bargiacchi and Brener were employees of Blueprint Medicines at the time of the research study. This study was presented as a poster at the AMCP Virtual Learning Event, April 2021.

Performance validity tests (PVTs) and symptom validity tests (SVTs) detect inaccuracies in examinee-completed measures, though methods for assessing the accuracy of informant reports-which may be inaccurate due to examinee deception, motivation for external incentives (e.g., disability payments), or attempts to validate examinee experiences-remain underexplored. We used a sample of 72 veteran-informant dyads undergoing evaluation of possible epilepsy-related neurocognitive disorder to assess the association between examinee response invalidity (i.e., performance and/or symptom invalidity) and informant report measures. Examinees completed PVTs, SVTs, cognitive, and self-report measures. Informants completed measures on examinee functioning and their own caregiver burden. Performance invalidity was defined as failure on two or more PVTs. Symptom invalidity for psychopathology symptom reports (SVT-P) and cognitive/somatic symptom reports (SVT-CS) were separately defined via above-threshold scores on two or more SVT criterion. Independent samples t tests demonstrated the associations of the PVT, SVT-CS, and SVT-P groups with informant-report measures. Informants for examinees with performance invalidity reported worse functioning in the examinee than informants for examinees in the valid performance group (medium-large effect sizes). Symptom validity status (for both SVT-CS and SVT-P) was meaningfully but less strongly related to informant-reported examinee functioning (small-medium effect sizes). Neither performance nor symptom invalidity was meaningfully related to informant-reported caregiver burden (negligible effect sizes). Informant reports for examinees with response invalidity should be interpreted with caution. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Objective: The aim of this study was to assess the impact race and language have on emergency department (ED) triage scores while accounting for illness severity. We hypothesized that non-White and non-English-speaking patients were assigned lower-acuity triage scores compared with White and English-speaking patients, respectively., Methods: We used a chart review-based retrospective cohort study design, examining patients aged 0 to 17 years at our pediatric ED from July 2015 through June 2016. Illness severity was measured using a truncated Modified Pediatric Early Warning Score calculated from patient vital signs. We used univariate and multivariate multinomial logistic regression to assess the association between race and language with Emergency Severity Index scores., Results: Our final data set consisted of 10,815 visits from 8928 patients. Non-Hispanic (NH) White patients accounted for 34.6% of patients. In the adjusted analyses, non-White patients had significantly reduced odds of receiving a score of 2 (emergency) (odds ratio [OR], 0.4; 95% confidence interval [CI], 0.33-0.49) or 3 (urgent) (OR, 0.5; 95% CI, 0.45-0.56) and significantly higher odds of receiving a score of 5 (minor) (OR, 1.34; 95% CI, 1.07-1.69) versus a score of 4 (nonurgent). We did not find a consistent disparity in Emergency Severity Index scores when comparing English- and non-English-speaking patients., Conclusions: We confirm that non-White patients receive lower triage scores than White patients. A more robust tool is required to account for illness severity and will be critical to understanding whether the relationship we describe reflects bias within the triage system or differences in ED utilization by racial groups., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

We describe a nurse-led project that aimed to assist a permanent supportive housing facility for chronically homeless individuals to improve medication adherence by refining a medication management program. Client and staff engagement through needs assessment, feedback, and evaluation formed the foundation for a sustainable medication management program.

Background: The metabolic demands associated with critical illness place patients at risk for nutrition deficits. Carnitine is a small molecule essential for fatty acid oxidation and gluconeogenesis. Secondary carnitine deficiency can have clinically significant complications and has been observed anecdotally in patients receiving extracorporeal membrane oxygenation (ECMO) therapy at our institution. Guidelines for monitoring and supplementing carnitine are lacking. This retrospective study determined whether critically ill pediatric patients receiving ECMO have an increased risk of carnitine deficiency., Methods: Acylcarnitine analysis was performed on residual specimens from patients who received ECMO therapy. The control data were a convenience sample gathered by chart review of patients who had been tested for carnitine during a hospitalization., Results: Acylcarnitines were measured in 217 non-ECMO patients and 81 ECMO patients. Carnitine deficiency, based on age-specific reference ranges, was observed in 41% of ECMO cases compared with 21% of non-ECMO cases. Multivariable analysis of age-matched patients identified that the odds of carnitine deficiency were significantly lower among patients on the floor compared with ECMO patients (odds ratio, 0.21; 95% CI, 0.10-0.44). Age-specific frequency of qualitative carnitine deficiency ranged from 15% (patients >5 years old) to 56% (patients 1 week to 1 month old) in ECMO patients and 15% (patients >5 years old) to 34% (patients 1-5 years old) in non-ECMO patients., Conclusion: In this study, ECMO patients were carnitine deficient more frequently compared with other inpatients, with the highest rates of deficiency among ECMO patients between 1 week and 1 month old., (© 2021 The Authors. Journal of Parenteral and Enteral Nutrition published by Wiley Periodicals LLC on behalf of American Society for Parenteral and Enteral Nutrition.)

Background and Objectives: Most young infants presenting to the emergency department (ED) with a brief resolved unexplained event (BRUE) are hospitalized. We sought to determine the rate of explanatory diagnosis after hospitalization for a BRUE., Methods: This was a multicenter retrospective cohort study of infants hospitalized with a BRUE after an ED visit between October 1, 2015, and September 30, 2018. We included infants without an explanatory diagnosis at admission. We determined the proportion of patients with an explanatory diagnosis at the time of hospital discharge and whether diagnostic testing, consultation, or observed events occurring during hospitalization were associated with identification of an explanatory diagnosis., Results: Among 980 infants hospitalized after an ED visit for a BRUE without an explanatory diagnosis at admission, 363 (37.0%) had an explanatory diagnosis identified during hospitalization. In 805 (82.1%) infants, diagnostic testing, specialty consultations, and observed events did not contribute to an explanatory diagnosis, and, in 175 (17.9%) infants, they contributed to the explanatory diagnosis (7.0%, 10.0%, and 7.0%, respectively). A total of 15 infants had a serious diagnosis (4.1% of explanatory diagnoses; 1.5% of all infants hospitalized with a BRUE), the most common being seizure and infantile spasms, occurring in 4 patients., Conclusions: Most infants hospitalized with a BRUE did not receive an explanation during the hospitalization, and a majority of diagnoses were benign or self-limited conditions. More research is needed to identify which infants with a BRUE are most likely to benefit from hospitalization for determining the etiology of the event., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

The coronavirus disease 2019 (COVID-19) pandemic forced schools to close in spring 2020, affecting the ability of school-based health centers (SBHCs) to serve youth and families who relied on their services. This preliminary study aimed to understand the implications of school closures on SBHC operations. Survey data were collected from a convenience sample of representatives from 427 SBHCs, representing approximately one sixth of SBHCs nationwide. When schools closed in spring 2020, 77% of SBHCs closed temporarily, 5% closed permanently, and 12% remained physically open. Telehealth was a crucial strategy used to continue delivering essential services. The percentage reporting any telehealth service offering before and after school closures increased by over 200%. Yet they also reported challenges, including financial and policy restraints. Many SBHCs that closed temporarily did so because their host schools closed, suggesting that making arrangements to remain open if a similar situation to the COVID-19 pandemic should arise might be beneficial. SBHCs are a proven cost-effective model to deliver health care in resource-limited communities. These preliminary study results indicate that SBHCs maintained service delivery following school closures, though many faced challenges. Further research is needed to fully understand the pandemic's impacts on SBHC service provision and health access and outcomes.

Background: The accuracy of the risk criteria for brief resolved unexplained events (BRUEs) from the American Academy of Pediatrics (AAP) is unknown. We sought to evaluate if AAP risk criteria and event characteristics predict BRUE outcomes., Methods: This retrospective cohort included infants <1 year of age evaluated in the emergency departments (EDs) of 15 pediatric and community hospitals for a BRUE between October 1, 2015, and September 30, 2018. A multivariable regression model was used to evaluate the association of AAP risk factors and event characteristics with risk for event recurrence, revisits, and serious diagnoses explaining the BRUE., Results: Of 2036 patients presenting with a BRUE, 87% had at least 1 AAP higher-risk factor. Revisits occurred in 6.9% of ED and 10.7% of hospital discharges. A serious diagnosis was made in 4.0% (82) of cases; 45% (37) of these diagnoses were identified after the index visit. The most common serious diagnoses included seizures (1.1% [23]) and airway abnormalities (0.64% [13]). Risk is increased for a serious underlying diagnosis for patients discharged from the ED with a history of a similar event, an event duration >1 minute, an abnormal medical history, and an altered responsiveness ( P < .05). AAP risk criteria for all outcomes had a negative predictive value of 90% and a positive predictive value of 23%., Conclusions: AAP BRUE risk criteria are used to accurately identify patients at low risk for event recurrence, readmission, and a serious underlying diagnosis; however, their use results in the inaccurate identification of many patients as higher risk. This is likely because many AAP risk factors, such as age, are not associated with these outcomes., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Increasing regionalization of pediatric care has led to interfacility transfer of children with general pediatric conditions at rates similar to those of high-risk adults, which may delay appropriate treatment. We sought to identify common medical diagnoses that did not require significant advanced intervention and that had high rates of discharge within 1 day of interfacility transfer. Using the Pediatric Health Information System (PHIS) database, we identified all transfers into PHIS-participating children's hospitals in 2019. We excluded encounters for mental health, labor/maternity, primary newborn diagnoses, and direct admissions to an intensive care unit. Eligible encounters were categorized by duration of hospitalization and basic vs advanced intervention after transfer. Of 286,905 transfers, 197,386 (68.6%) met inclusion criteria. Cough, febrile seizures, croup, and allergic reactions required advanced interventions <10% of the time, and patients with these diagnoses were most commonly discharged within 1 day after transfer. These conditions are potential targets for building pediatric capacity in non-pediatric hospitals.

Objectives: To evaluate International Classification of Diseases, 10th Revision (ICD-10) coding strategies for the identification of patients with a brief resolved unexplained event (BRUE)., Methods: Multicenter retrospective cohort study, including patients aged <1 year with an emergency department (ED) visit between October 1, 2015, and September 30, 2018, and an ICD-10 code for the following: (1) BRUE; (2) characteristics of BRUE; (3) serious underlying diagnoses presenting as a BRUE; and (4) nonserious diagnoses presenting as a BRUE. Sixteen algorithms were developed by using various combinations of these 4 groups of ICD-10 codes. Manual chart review was used to assess the performance of these ICD-10 algorithms for the identification of (1) patients presenting to an ED who met the American Academy of Pediatrics clinical definition for a BRUE and (2) the subset of these patients discharged from the ED or hospital without an explanation for the BRUE., Results: Of 4512 records reviewed, 1646 (36.5%) of these patients met the American Academy of Pediatrics criteria for BRUE on ED presentation, 1016 (61.7%) were hospitalized, and 959 (58.3%) had no explanation on discharge. Among ED discharges, the BRUE ICD-10 code alone was optimal for case ascertainment (sensitivity: 89.8% to 92.8%; positive predictive value: 51.7% to 72.0%). For hospitalized patients, ICD-10 codes related to the clinical characteristics of BRUE are preferred (specificity 93.2%, positive predictive value 32.7% to 46.3%)., Conclusions: The BRUE ICD-10 code and/or the diagnostic codes for the characteristics of BRUE are recommended, but the choice between approaches depends on the investigative purpose and the specific BRUE population and setting of interest., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Introduction: In response to COVID-19, schools rapidly transitioned to virtual learning. School-based health centers (SBHCs) required immediate shifts from in-person to telehealth services to continue supporting students., Method: A qualitative analysis of nationally-led "Listening and Learning" sessions by the School-Based Health Alliance revealed substantial innovation and expansion of telehealth services., Results: Providers and sponsoring organizations shared challenges and mechanisms for troubleshooting barriers during online webinars to provide support, education, and resources to SBHCs., Discussion: Lessons learned during the COVID-19 pandemic demonstrate the value of SBHCs, which continue to target barriers to health care access, protect the most vulnerable, and decrease the spread of disease. Telehealth implementation by SBHCs can support schools and communities, mitigate future strain on the health care system by continuing to keep youth from over-burdened emergency departments and provide needed mental health care. State and federal policy changes can ensure the continued provision of telehealth by SBHCs for disadvantaged youth., (Copyright © 2020 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the effect of a standardized feeding approach using a clinical nutrition pathway on weight-for-age Z score (WAZ) over hospital length of stay (HLOS) for infants with congenital heart disease (CHD)., Study Design: A 10-year retrospective cohort study examined eligible infants who underwent neonatal cardiac surgery between July 2009 and December 2018 (n = 987). Eligibility criteria included infants born at least 37 weeks of gestation and a minimum birth weight of 2 kg who underwent cardiac surgery for CHD within the first 30 days of life. Using the best linear unbiased predictions from a linear mixed effects model, WAZ change over HLOS was estimated before and after January 2013, when the standardized feeding approach was initiated. The best linear unbiased predictions model included adjustment for patient characteristics including sex, race, HLOS, and class of cardiac defect., Results: The change in WAZ over HLOS was significantly higher from 2013 to 2018 than from 2009 to 2012 (β = 0.16; SE = 0.02; P < .001), after controlling for sex, race, HLOS, and CHD category, indicating that infants experienced a decreased WAZ loss over HLOS after the standardized feeding approach was initiated. Additionally, differences were found in WAZ loss over HLOS between infants with single ventricle CHD (β = 0.26; SE = 0.04; P < .001) and 2 ventricle CHD (β = 0.04; SE = 0.02; P = .04)., Conclusions: These data suggest that an organized, focused approach for nutrition therapy using a standardized pathway improves weight change outcomes before hospital discharge for infants with single and 2 ventricle CHD who require neonatal cardiac surgery., (Copyright © 2020 Elsevier Inc. All rights reserved.)

With a rapid shift to telehealth during the coronavirus disease 2019 (COVID-19) pandemic, clinicians, health care organizations, and policy makers must consider and address patients' evolving needs, concerns, and expectations.

Background: Hyperglycaemia may contribute to failure to recover from pulmonary exacerbations in cystic fibrosis (CF). We aimed to evaluate the prevalence and mechanism of hyperglycaemia during and post-exacerbations., Methods: Nine paediatric CF patients, not on insulin, hospitalized for intravenous antibiotics, underwent an oral glucose tolerance test (OGTT) and continuous glucose monitoring (CGM) upon admission (visit 1) and an OGTT 2 weeks (visit 2) and 6 weeks to 12 months later when at stable baseline (visit 3). Insulin and glucose levels were measured before, 30, 60 and 120 min after glucose ingestion during OGTT. Hyperglycaemia on OGTT was defined according to the American Diabetes Association criteria as abnormal OGTT or consistent with diabetes. Hyperglycaemia on CGM was defined as CGM time above 140 mg/dL > 4.5%., Results: At visit 1, 8/9 patients had hyperglycaemia on both CGM and OGTT (2 diabetes and 6 abnormal OGTT). At visit 2, 5/8 had hyperglycaemia (all abnormal OGTT). At visit 3, (median (IQR) time since visit 1, 4.9 (3.8-6.3) months), 5/7 had hyperglycaemia (2 diabetes and 3 abnormal OGTT). At visits 1, 2 and 3, respectively, mean (SD) 2-hour OGTT glucose was 175.8 (42.3), 146.3 (31.9) and 176.9 (51.7) mg/dL. CGM time above 140 mg/dL at visit 1 was 25.3% (16.9). Insulin AUC decreased from visit 2 (median (IQR) 5449 (3321-8123) mcIU-min/mL) to visit 3 (3234 (2913-3680) mcIU-min/mL)., Conclusion: Hyperglycaemia is prevalent during paediatric CF exacerbations; it appears to improve with exacerbation treatment but to worsen later in association with decreased insulin secretion., Competing Interests: None., (© 2020 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Importance: With the approval of avapritinib for adults with unresectable or metastatic gastrointestinal stromal tumors (GISTs) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 variant, including PDGFRA D842V variants, and National Comprehensive Cancer Network guideline recommendations as an option for patients with GIST after third-line treatment, it is important to estimate the potential financial implications of avapritinib on a payer's budget., Objective: To estimate the budget impact associated with the introduction of avapritinib to a formulary for metastatic or unresectable GISTs in patients with a PDGFRA exon 18 variant or after 3 or more previous treatments from the perspective of a US health plan., Design, Setting, and Participants: For this economic evaluation, a 3-year budget impact model was developed in March 2020, incorporating costs for drug acquisition, testing, monitoring, adverse events, and postprogression treatment. The model assumed that avapritinib introduction would be associated with increased PDGFRA testing rates from the current 49% to 69%. The health plan population was assumed to be mixed 69% commercial, 22% Medicare, and 9% Medicaid. Base case assumptions included a GIST incidence rate of 9.6 diagnoses per million people, a metastatic PDGFRA exon 18 mutation rate of 1.9%, and progression rate from first-line to fourth-line treatment of 17%., Exposures: The model compared scenarios with and without avapritinib in a formulary., Main Outcomes and Measures: Annual, total, and per member per month (PMPM) budget impact., Results: In a hypothetical 1-million member plan, fewer than 0.1 new patients with a PDGFRA exon 18 variant per year and 1.2 patients receiving fourth-line therapy per year were eligible for treatment. With avapritinib available, the total increase in costs in year 3 for all eligible adult patients with a PDGFRA exon 18 variant was $46 875, or $0.004 PMPM. For patients undergoing fourth-line treatment, the total increase in costs in year 3 was $69 182, or $0.006 PMPM. The combined total budget impact in year 3 was $115 604, or $0.010 PMPM, including an offset of $3607 in postprogression costs avoided or delayed. The higher rates of molecular testing resulted in a minimal incremental testing cost of $453 in year 3., Conclusions and Relevance: These results suggest that adoption of avapritinib as a treatment option would have a minimal budget impact to a hypothetical US health plan. This would be primarily attributable to the small eligible patient population and cost offsets from reduced or delayed postprogression costs.

Rationale: In cystic fibrosis (CF), the lung clearance index (LCI), derived from multiple breath washout (MBW), is more sensitive in detecting early lung disease than FEV 1 ; MBW has been less thoroughly evaluated in young patients with primary ciliary dyskinesia (PCD). Objectives: Our objectives were 1 ) to evaluate the sensitivity of MBW and spirometry for the detection of mild lung disease in young children with PCD and CF compared with healthy control (HC) subjects and 2 ) to compare patterns of airway obstruction between disease populations. Methods: We used a multicenter, single-visit, observational study in children with PCD and CF with a forced expiratory volume in 1 second (FEV 1 ) greater than 60% predicted and HC subjects, ages 3-12 years. Nitrogen MBW and spirometry were performed and overread for acceptability. χ 2 and Kruskall-Wallis tests compared demographics and lung function measures between groups, linear regression evaluated the effect of disease state, and Spearman's rank correlation coefficient compared the LCI and spirometric measurements. Results: Twenty-five children with PCD, 49 children with CF, and 80 HC children were enrolled, among whom 17 children with PCD (68%), 36 children with CF (73%), and 53 (66%) HC children performed both acceptable spirometry and MBW; these children made up the analytic cohort. The median age was 9.0 years (interquartile range [IQR], 6.8-11.1). The LCI was abnormal (more than 7.8) in 10 of 17 (59%) patients with PCD and 21 of 36 (58%) patients with CF, whereas FEV 1 was abnormal in three of 17 (18%) patients with PCD and six of 36 (17%) patients with CF. The LCI was significantly elevated in patients with PCD and CF compared with HC subjects (ratio of geometric mean vs. HC: PCD 1.27; 95% confidence interval [CI], 1.15-1.39; and CF 1.24; 95% CI, 1.15-1.33]). Children with PCD had lower midexpiratory-phase forced expiratory flow % predicted compared with children with CF (62% [IQR, 50-78%] vs. 85% [IQR, 68-99%]; P  = 0.05). LCI did not correlate with FEV 1 . Conclusions: The LCI is more sensitive than FEV 1 in detecting lung disease in young patients with PCD, similar to CF. LCI holds promise as a sensitive endpoint for the assessment of early PCD lung disease.

Background: SOT is the treatment of choice for end-stage organ disease. Improved long-term survival after NKSOT has uncovered chronic morbidity including CKD. AKI is common after NKSOT and may be associated with long-term CKD., Methods: We performed a retrospective cohort study looking at AKI and CKD after pediatric heart (n = 109) or liver (n = 112) transplant. AKI was defined using KDIGO creatinine-based criteria. pAKI was AKI ≤ 7 days post-transplant; CKD 3-5 was eGFR < 60 mL/min/1.73 m 2 by modified Schwartz formula for > 3 months. We looked at the incidence of CKD 3-5 and the effect of perioperative pAKI on the slope of eGFR post-transplant., Results: pAKI was seen in 63% (n = 69) after heart and 38% (n = 43) after liver transplant. pAKI was associated with longer ICU and hospital stays. Cumulative incidence (95% CI) of CKD 3-5 at 60 months post-heart transplant was 40.9% (27.9%-57.1%) in patients with AKI vs 35.8% (17.1%-64.8%) in those without (P = NS). Post-liver transplant, the cumulative incidence of CKD 3-5 at 60 months was 0% in those without pAKI vs 10% (3.2%-29.3%) in those with (P = .01). Patients with pAKI had lower eGFR at last follow-up., Conclusion: pAKI and CKD are common after NKSOT. Incidence of CKD is higher in those with pAKI. AKI episodes are associated with a drop in eGFR during follow-up. Identifying patients who have had AKI is an important first step in identifying those at risk of repeated AKI episodes. These patients would benefit from closer monitoring for CKD, lower nephrotoxic drug use, and follow-up with nephrology., (© 2020 Wiley Periodicals LLC.)

Objective: The number of women veterans seeking Veterans Health Administration services has substantially increased over the past decade. Neuropsychology remains an understudied area in the examination of gender differences. The present study sought to delineate similarities and differences in men and women veterans presenting for neuropsychological evaluation in terms of demographics, referral, medical conditions, effort, and outcome diagnosis., Method: A database collected from an outpatient VA neuropsychology clinic from 2013 to 2019 was analyzed (n = 232 women, 2642 men). Additional analyses examined younger (n = 836 men, 155 women) and older (n = 1805 men, 77 women) age cohorts., Results: Women veterans were younger and more educated than men, whereas men had higher prevalence of vascular risk factors. Both groups were most often referred from mental health clinics and memory was the most common referral question. Although men performed worse on performance validity measures, clinicians rated women as evidencing poorer effort on a cumulative rating based on formal and embedded performance validity measures, behavioral observations, and inconsistent test patterns. Older women reported more depressive symptoms than older men and were more commonly diagnosed with depression., Conclusions: This exploratory study fills a gap in the understanding of gender differences in veterans presenting for neuropsychological evaluations. Findings emphasize consideration for the intersection of gender with demographics, medical factors, effort, and psychological symptoms by VA neuropsychologists. A better understanding of relationships between gender and these factors may inform neuropsychologists' test selection, interpretation of behavioral observations, and diagnostic considerations to best treat women veterans., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Pakistan ranks third globally in the number of unvaccinated and under-vaccinated children, and Sindh province has one of the lowest vaccination rates in the country. Electronic census-based immunization information systems have the potential to bolster traditional immunization service delivery mechanisms, but literature has largely not focused on implementation at scale in Pakistan. This is a case report of technical support provided to the Sindh Department of Health/Expanded Program on Immunization (DOH/EPI) from 2015 to 2017 to strengthen routine immunization (RI). The program developed an immunization information system used by district health officers to register and track individual immunization status, improve vaccine logistics, and generate more accurate population estimates and vaccination targets. District immunization officers (DIOs) assisted their district health management teams and supervisors to use registration and service data stored in the immunization information system database to prepare microplans, monitor catchment area performance, and solve problems. Civil society partners registered 830,610 children (aged 0 to 23 months) and 348,315 pregnant women in 28,565 villages over an 18-month intensive intervention period. By the end of this period, 65% of all registered women had been vaccinated with two or more doses of the tetanus toxoid vaccine (compared to 26% at baseline); Penta 3 vaccination coverage had increased from 27% to 64%; and 52% of the registered children (aged 0 to 23 months) were fully immunized (compared to 18% at baseline). The immunization information system helped district managers identify and focus limited resources on high-risk populations; reminded families and health providers when vaccinations were due or missed; assisted managers in monitoring vaccination coverage, vaccinator performance, and vaccine stocks; and encouraged local problem solving to improve RI performance. The Government of Sindh demonstrated a commitment to RI based on the program's results, which bode well to future enhancements and scale up., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/mhealth.2020.01.07). ES reports grants from USAID, during the conduct of the study. TM reports grants from USAID, during the conduct of the study. WJ reports grants from USAID, during the conduct of the study. KB reports grants from United States Agency for International Development, during the conduct of the study.SO reports grants from USAID, during the conduct of the study. PR reports other from USAID, during the conduct of the study. SMAG reports other from USAID, during the conduct of the study., (2020 mHealth. All rights reserved.)

Importance: Obtaining informed consent is an important ethical obligation for clinical research participation that is imperfectly implemented. Research on improving consent processes often focuses on consent forms, but little is known about consent forms' influence on decision-making compared with other types of engagement., Objective: To evaluate whether parents decide whether to enroll their children in research before or after they receive the consent form., Design, Setting, and Participants: An online survey of 88 parents who enrolled or declined to enroll their child in a weight management intervention study between January 2, 2018, and June 24, 2019, was conducted; surveys were completed between February 2, 2018, and July 9, 2019. A 31-item survey asked about impressions of the study throughout the enrollment process, timing of enrollment decisions, and decision-making factors. Responses were summarized descriptively and subgroups were compared using the Fisher exact test or χ2 test., Main Outcomes and Measures: Self-reported timing of enrollment decision., Results: A total of 106 parents were approached and gave permission for their contact information to be shared with the study team; 22 additional parents declined to allow their information to be shared, and 24 lost contact with the partner study before they could be asked for permission. A total of 88 parents (67 enrollees, 21 decliners) completed the survey (83% participation rate); 79 of 88 reporting gender (instead of sex, as biological sex was not relevant to survey) information were women (91%), 66 participants (75%) were non-Hispanic White, and 63 participants (72%) had annual household incomes greater than or equal to $70 000. No significant differences in respondent characteristics between enrollees and decliners were identified. Fifty-nine parents (67%) responded that they decided whether to enroll in the weight management study before receiving the consent form. Only 17 of 69 parents (25%) who remembered receiving the consent form responded that it taught them new information., Conclusions and Relevance: The findings of this study suggest that interventions to improve informed consent forms may have limited influence on decision-making because many research decisions occur before review of the consent form. It appears that regulatory review and interventions to improve decision-making should focus more on early engagement (eg, recruitment materials). Future studies should test timing of decisions in other types of research with different populations and clinical settings.

Background: Morphea is an inflammatory and fibrosing condition that affects the skin and subcutaneous structures. Morphea is managed by dermatologists, rheumatologists, or both. Prior studies have suggested there is significant variability in approach to treatment. In 2012, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) published consensus treatment plans (CTPs) for pediatric morphea to develop more standardized treatment plans for patients requiring systemic therapy. We aimed to assess whether the publication of CTPs has impacted care of patients with morphea at our institution., Methods: Data were collected via a retrospective review of medical records of 61 pediatric patients diagnosed with morphea at Seattle Children's Hospital (SCH) from January 1, 2005, to December 12,2017., Results: Prior to the publication of CTPs, 2 out of 24 patients (8.3%) were treated with a regimen that matched a subsequent CTP. After publication of CTPs, 29 out of 37 patients (78.4%) were treated with a regimen that matched a CTP (P < 0.001). A subanalysis was performed to assess the number of patients who needed second- or third-line therapies. Of those who followed a CTP therapy plan (n = 26), 3 patients (11.5%) needed a second-line therapy compared with 11 patients (44%) in the no-CTP followed group (n = 25), (P = 0.012)., Conclusions: The publication of CTPs led to a significant change in treatment approach for patients with morphea requiring systemic therapy at SCH. Patients treated with one of the treatment plans recommended by the CTPs were less likely to need second-line systemic therapy., (© 2020 Wiley Periodicals, Inc.)

Objectives: Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection, is a leading cause of death and disability among children worldwide. Identifying sepsis in pediatric patients is difficult and can lead to treatment delay. Our objective was to assess the host proteomic response to infection utilizing an aptamer-based multiplexed proteomics approach to identify novel serum protein changes that might help distinguish between pediatric sepsis and infection-negative systemic inflammation and hence can potentially improve sensitivity and specificity of the diagnosis of sepsis over current clinical criteria approaches., Design: Retrospective, observational cohort study., Setting: PICU and cardiac ICU, Seattle Children's Hospital, Seattle, WA., Patients: A cohort of 40 children with clinically overt sepsis and 30 children immediately postcardiopulmonary bypass surgery (infection-negative systemic inflammation control subjects) was recruited. Children with sepsis had a confirmed or suspected infection, two or more systemic inflammatory response syndrome criteria, and at least cardiovascular and/or pulmonary organ dysfunction., Interventions: None., Measurements and Main Results: Serum samples from 35 of the sepsis and 28 of the bypass surgery subjects were available for screening with an aptamer-based proteomic platform that measures 1,305 proteins to search for large-scale serum protein expression pattern changes in sepsis. A total of 111 proteins were significantly differentially expressed between the sepsis and control groups, using the linear models for microarray data (linear modeling) and Boruta (decision trees) R packages, with 55 being previously identified in sepsis patients. Weighted gene correlation network analysis helped identify 76 proteins that correlated highly with clinical sepsis traits, 27 of which had not been previously reported in sepsis., Conclusions: The serum protein changes identified with the aptamer-based multiplexed proteomics approach used in this study can be useful to distinguish between sepsis and noninfectious systemic inflammation.

Objective: To determine the prevalence of vitamin D deficiency among individuals with traumatic brain injury (TBI) undergoing acute inpatient rehabilitation., Setting: Inpatient rehabilitation., Participants: Participants were admitted from November 1st, 2010 through June 30th, 2015 with diagnosis of mild-severe TBI and had serum 25 OH vitamin D levels checked upon admission. 369 out of 845 met inclusion., Design: Retrospective cohort., Main Measures: 25 OH vitamin D, vitamin D treatment., Results: The majority of patients were male (67%), Caucasian (89%) with private insurance (61%) and a mean age of 43.5±21.0 years. 25 OH vitamin D levels were categorized: deficient (<20 ng/mL), insufficient (20-29.9 ng/mL), and sufficient (≥30 ng/mL). There were 95 (26%) patients that were deficient, 131 (36%) that were insufficient, and 143 (39%) that were sufficient. Race/ethnicity was found to be significant (p = 0.0145) with the largest percentage of Hispanics found in the insufficient and deficient categories, and the largest percentage of Blacks in the deficient category. Most patients with deficient or insufficient vitamin D levels were prescribed vitamin D replacement during their rehab stay (p < 0.0001)., Conclusion: The majority of patients undergoing acute inpatient rehabilitation were found to have insufficient or deficient vitamin D levels, therefore it should be routinely screened and treated as indicated.

The outermost surface of insect cuticle is a high-performance interface that provides wear protection, hydration, camouflage and sensing. The complex and inhomogeneous structure of insect cuticle imposes stringent requirements on approaches to elucidate its molecular structure and surface chemistry. Therefore, a molecular understanding and possible mimicry of the surface of insect cuticle has been a challenge. Conventional optical and electron microscopies as well as biochemical techniques provide information about morphology and chemistry but lack surface specificity. We here show that a near edge X-ray absorption fine structure microscope at the National Synchrotron Light Source can probe the surface chemistry of the curved and inhomogeneous cuticle of the African flower scarab. The analysis shows the distribution of organic and inorganic surface species while also hinting at the presence of aragonite at the dorsal protrusion region of the Eudicella gralli head, in line with its biological function.

Aim: To compare the differences of glucose metabolism outcomes between treatment-naïve, patients with first episode psychosis (FEP) and mood disorders., Methods: We conducted a systematic review and meta-analysis of glucose intolerance in treatment-naïve, first episode patients with severe mental illnesses (SMIs)., Results: We identified 31 eligible studies. Compared to healthy controls, FEP group have higher insulin and insulin resistance levels, and both groups have higher glucose tolerance test results. No significant differences were found in glucose metabolism outcomes between FEP and mood disorder groups., Conclusions: Our results highlight impaired glucose metabolism at the onset of SMIs, suggesting both patients with psychosis and mood disorders are high-risk groups for diabetes development., (© 2018 John Wiley & Sons Australia, Ltd.)

With increasing recognition of the important relationship between oral and systemic health, non-dental health professions schools and programs are now teaching their students about oral health in various ways. This study built on surveys of medical schools, primary care residency and fellowship programs, and other health professions programs conducted by the authors in 2017, which found some had made significant progress in integrating oral health into primary care training, while others lagged behind. The aim of the current study was to better understand the characteristics and climate of oral health education in non-dental health professions schools by conducting interviews with leaders of programs who had self-identified in the surveys as having a robust oral health curriculum. Hour-long interviews were conducted between October 2017 and March 2018 with 31 program directors or deans of medical specialty and allied health professions programs using a semi-structured interview guide. These interviewees were from 13 health disciplines. The coding of interview transcripts identified seven major themes: motivations to develop an oral health curriculum; rationale for curriculum topics covered; best aspects of the curriculum; evaluation and assessment strategies; relationships with dental providers and residents and dental hygienists; barriers and challenges; and advice and lessons learned. The interviewees reported a strong belief that oral health is an important health topic. Key elements that interviewees identified as helping them build robust oral health programs in their primary care curricula were the following: having an oral health champion; having some funding; building relationships with dental professionals; using local, state, and national resources; using curricular materials from existing sources; incorporating skills-based sessions; taking an IPE approach; and making oral health part of what the program already does. These findings should be useful for primary care schools and programs that are beginning to add oral health to their curricula and those seeking to improve their existing oral health education for their students.

Potentially traumatizing events (PTE) are highly prevalent, and are associated with detrimental effects on psychological health, including increased risk of posttraumatic stress disorder (PTSD). Multiple endorsed PTEs (polytraumatization) may have even greater effects on a person's health than the impact of a single index event. To better understand patterns of polytraumatization, person-centered analytic techniques such as Latent class analysis (LCA) are recommended. The current study used LCA to explore latent subgroupings of people based on their endorsement of PTEs, thus defining patterns in PTE exposure. The sample included 850 participants who endorsed at least one PTE on a web-administered Trauma History Questionnaire (THQ). Results indicated a best-fitting 3-class solution: (1) a class with a greater probability of experiencing interpersonal PTEs and other PTEs, (2) a class with moderate PTE exposure and higher probability of mugging and accidents, and (3) a class with low PTE exposure. Differences in age, gender, and PTSD symptom severity accounted for class membership. Results suggest the experience of interpersonal PTEs may be a risk factor for additional lifetime PTE exposure, and is associated with increased PTSD severity. Additional findings underscore the heterogenity of trauma experiences, highlighting the importance of examining such patterns in future research., (Copyright © 2017. Published by Elsevier B.V.)

Objective: The present study examined the relationship between posttraumatic stress symptoms (PTSS) and depression symptoms with hospital outcome measures to explore how psychiatric factors relate to hospital length of stay (LOS)., Method: Participants were adults admitted to a large Level I Trauma Center for longer than 24h. Depression was assessed at hospitalization using the Patient Health Questionnaire (PHQ-8), and PTSS was measured by the Primary Care PTSD Screen (PC-PTSD). Hospital outcome information was collected from the hospital's trauma registry. Pearson correlations were performed., Results: 460 participants (mean age=44years, SD=16.8; 65.4% male) completed the study. Baseline PTSS and depression were significantly correlated with longer hospital LOS while controlling for demographics and injury severity (p=0.026; p=0.023). Both PTSS-positive and depression-positive groups had an average increased hospital LOS of two days., Conclusions: A significant proportion of individuals who are admitted to the hospital following trauma may be at risk for depression and PTSS, which may then increase hospital LOS. As national attention turns to reducing healthcare costs, early screenings and interventions may aid in minimizing psychiatric symptoms in trauma patients, in turn reducing the cost and outcomes associated with total hospital LOS., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: SeptiCyte Lab (Immunexpress, Seattle, WA), a molecular signature measuring the relative expression levels of four host messenger RNAs, was developed to discriminate critically ill adults with infection-positive versus infection-negative systemic inflammation. The objective was to assess the performance of Septicyte Lab in critically ill pediatric patients., Design: Prospective observational study., Setting: Pediatric and Cardiac ICUs, Seattle Children's Hospital, Seattle, WA., Patients: A cohort of 40 children with clinically overt severe sepsis syndrome and 30 children immediately postcardiopulmonary bypass surgery was recruited. The clinically overt severe sepsis syndrome children had confirmed or highly suspected infection (microbial culture orders, antimicrobial prescription), two or more systemic inflammatory response syndrome criteria (including temperature and leukocyte criteria), and at least cardiovascular ± pulmonary organ dysfunction., Interventions: None (observational study only)., Measurements and Main Results: Next-generation RNA sequencing was conducted on PAXgene blood RNA samples, successfully for 35 of 40 (87.5%) of the clinically overt severe sepsis syndrome patients and 29 of 30 (96.7%) of the postcardiopulmonary bypass patients. Forty patient samples (~ 60% of cohort) were reanalyzed by reverse transcription-quantitative polymerase chain reaction, to check for concordance with next-generation sequencing results. Postcardiopulmonary bypass versus clinically overt severe sepsis syndrome descriptors included the following: age, 7.3 ± 5.5 versus 9.0 ± 6.6 years; gender, 41% versus 49% male; Pediatric Risk of Mortality, version III, 7.0 ± 4.6 versus 8.7 ± 6.4; Pediatric Logistic Organ Dysfunction, version II, 5.1 ± 2.2 versus 4.8 ± 2.8. SeptiCyte Lab strongly differentiated postcardiopulmonary bypass and clinically overt severe sepsis syndrome patients by receiver operating characteristic curve analysis, with an area-under-curve value of 0.99 (95% CI, 0.96-1.00). Equivalent performance was found using reverse transcription-quantitative polymerase chain reaction. There was no significant correlation between the score produced by the SeptiCyte Lab test and measures of illness severity, immune compromise, or microbial culture status., Conclusions: SeptiCyte Lab is able to discriminate clearly between clinically well-defined and homogeneous postcardiopulmonary bypass and clinically overt severe sepsis syndrome groups in children. A broader investigation among children with more heterogeneous inflammation-associated diagnoses and care settings is warranted.

The mind and the body are clearly intertwined in ways that are only now being discovered. In the orthopaedic world, injuries and diseases are often classified and described in a very organized, discrete fashion-The radius is fractured, the ACL or meniscus or rotator cuff is torn, the ankle is sprained, and/or the lumbar spine has a disc herniation. Although it is, in many ways, almost comforting to think about injuries or orthopaedic issues in this manner, what about the many patients who fail to fall into this classification? What about the thousands of patients with severe unexplained chronic pain or patients who just are not improving with the typical treatment algorithm. What about patients who present with multiple overlapping symptoms that do not fall into any of the classic diagnosis patterns? The mismatch between the actual health needs of typical patients and the standard acute medical response produces an immense waste of medical resources and incredible frustration for both the patient and the provider and creates a real risk that acute conditions will go untreated and become chronic. After more than a decade of traditional orthopaedic and musculoskeletal practice, its tremendous benefits as well as its limitations have become apparent. These limitations have sparked a search for integration of mind-body considerations to fill some of these gaps. Although this can prove to be quite challenging in today's healthcare world of maximizing volume and decreasing costs, it has proven to be an invaluable resource for both personal growth and patient and family satisfaction. The goals of this 2-part article are to dissect the relatively new concept of the mind-body connection in orthopaedics. The article aims to provide a framework that illustrates how the mind will predictably create objective observable phenomena in the body. The central focus of this framework is the role of the sympathetic nervous system and its effect on the chemistry, biomechanics, and appearance of various tissues in the body. Further identified are factors contributing to the aberrant emotional response as a means to empower practitioners and patients in recognizing the link between negative perception and observable symptoms. Our hope is to ultimately introduce a model of empowerment that when presented to a patient/family can produce a proactive response and, in turn, enhance current orthopaedic and pain management practices.

Background: Virtual reality (VR) technology has demonstrated usefulness in diagnosis, education, and training. Studies supporting use of VR as a therapeutic treatment in medical rehabilitation settings remain limited. This study examines the use of VR in a treatment capacity, and whether it can be effectively integrated into neurorehabilitation., Objective: To determine whether immersive VR treatment interventions improve executive dysfunction in patients with brain injury and whether performance is stronger on a VR version of the Stroop than traditional Stroop formats., Methods: 15 patients with brain injury admitted to day neurorehabilitation., Outcome Measures: reaction time, inhibition, and accuracy indices on VR Stroop; Automated Neuropsychological Assessment Metrics (ANAM) Stroop, Delis-Kaplan Executive Function System Stroop, Golden Stroop, and Woodcock-Johnson, 3rd Edition (WJ-III): Pair Cancellation., Results: Participants demonstrated significantly reduced response time on the word-reading condition of VR Stroop and non-significantly reduced response time on the interference condition. Non-significant improvements in accuracy and inhibition were demonstrated on the color-naming condition of VR Stroop. Significantly improved accuracy under time pressure was found for the ANAM, after VR intervention., Conclusion: Implementation of immersive VR interventions during neurorehabilitation is effective in improving specific executive functions and information processing speed in brain-injured patients during the subacute period.

Objective: For patients' preferences to be honored, emergency department (ED) physicians must be able to find and use advance care planning (ACP) information in the electronic medical record (EMR). ED physicians' experiences with ACP EMR documentation and their documentation needs are unknown., Methods: We surveyed 70 ED physicians (81% response rate) from a tertiary and county ED. Our primary outcome was confidence finding and using ACP EMR documentation (percentage reporting very/extremely on a five-point Likert scale). Secondary outcomes included frequency of use and perceived usefulness of types of ACP documentation. Suggestions for improvement were analyzed using thematic content analysis., Results: Participants' mean age was 36 years (± 9) and 54% were women. Thirty-one percent reported being very/extremely confident they could find ACP EMR documentation, and 55% felt very/extremely confident they could use it to care for patients. Yet 74% needed it ≥1 time/week and 43% ≥5 times/week. Participants reported code status orders (90%), Physician Orders for Life Sustaining Treatment (POLST) (86%), and durable power of attorney for health care (78%) as very/extremely useful, followed by values statements (31%), oral directives (34%), and living wills (37%). ED physicians wanted highly visible ACP information, "on the main screen.", Conclusions: EMR systems are not optimized to provide critical ACP information to ED physicians who lack confidence finding or using ACP EMR documentation to care for patients. Dedicated ACP information on the EMR home screen and tailored training may be needed to help ED providers find, use, and discuss ACP documentation to provide care aligned with patients' goals.

Many malignant cells release the NKG2D ligand ULBP2 from their cell surface to evade immunosurveillance by NK cells and CD8 T cells. Although the shedding mechanism remains unclear, various inhibitors of matrix metalloproteinases have been shown to efficiently block the release of soluble ULBP2. The clinical use of these inhibitors, however, is limited because of adverse side effects. Using high-throughput screening technique, we identified a specific inhibitor of phosphatase of regenerating liver 3 (PRL-3) that could reduce the level of soluble ULBP2 in the culture supernatant of various cancer cell lines. Inhibition or gene knockdown of PRL-3 did not reduce ULBP2 shedding, but rather suppressed posttranslational maturation of ULBP2, resulting in intracellular retention of immature ULBP2. We then found that ULBP2 was constitutively associated with heat shock protein HSP60. Complete maturation of ULBP2 required tyrosine phosphorylation of HSP60 which was mediated by PRL-3., (Copyright © 2015 by The American Association of Immunologists, Inc.)

Purpose: Killer-cell immunoglobulin-like receptors (KIRs) that regulate natural-killer cells are highly polymorphic. Some KIR2DL1 alleles encode receptors that have stronger signaling function than others. We tested the hypothesis that the clinical outcomes of allogeneic hematopoietic stem-cell transplantation (HSCT) could be affected by donor KIR2DL1 polymorphism., Patients and Methods: All 313 pediatric patients received allogeneic HSCT at a single institution. Donor KIR2DL1 functional allele typing was retrospectively performed using single nucleotide polymorphism assay., Results: Patients who received a donor graft containing the functionally stronger KIR2DL1 allele with arginine at amino acid position 245 (KIR2DL1-R(245)) had better survival (P = .0004) and lower cumulative incidence of disease progression (P = .001) than those patients who received a donor graft that contained only the functionally weaker KIR2DL1 allele with cysteine at the same position (KIR2DL1-C(245)). The effect of KIR2DL1 allelic polymorphism was similar in patients with acute myeloid leukemia or acute lymphoblastic leukemia among all allele groups (P ≥ .71). Patients who received a KIR2DL1-R(245)-positive graft with HLA-C receptor-ligand mismatch had the best survival (P = .00003) and lowest risk of leukemia progression (P = .0005) compared with those who received a KIR2DL1-C(245) homozygous graft., Conclusion: Donor KIR2DL1 allelic polymorphism affects recipient outcomes after allogeneic HSCT. These findings have substantial implications for prognostication and donor selection.

Background: Genetic variation in monoamine oxidase A (MAOA) and serotonin transporter (5-HTT)-linked polymorphic regions (LPR) is associated with neuropsychiatric behavior., Methods: We genotyped 37 macaques using conventional PCR product gel fractionation and by capillary electrophoresis of multiplexed amplicons and compared the data., Results: Genotype concordance was 97% and 95% for MAOA-LPR and 5-HTT-LPR, respectively. Capillary electrophoresis was more sensitive and cost-effective., Conclusions: Multiplexing MAOA-LPR and 5-HTT-LPR will enhance the genotyping of large sample sets., (© 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.)