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Context: Children and adolescents with cancer experiencing complex symptoms can benefit from subspeciality palliative care. However, standardized methods of symptom documentation by pediatric palliative care teams are lacking. Understanding current approaches to symptom documentation will inform next steps to optimize symptom support., Objective: To explore the documentation of symptom prevalence and characteristics in unstructured clinical notes by pediatric palliative care clinicians caring for children and adolescents with cancer., Methods: We reviewed unstructured clinical notes documented by the pediatric palliative care team for 115 children and adolescents with cancer. Symptom-related data were abstracted and evaluated using content analysis based on the Memorial Symptom Assessment Scale 10-18 instrument items. We also evaluated documentation of severity and distress for six commonly experienced symptoms in pediatric cancer: difficulty sleeping; feelings of sadness; lack of energy; nausea/vomiting; pain; and worry., Results: We identified 1420 symptoms in 662 clinical notes for 106 patients. We identified a median of 5 individual symptoms (IQR = 3-8.5) per patient. Pain was the most frequently documented symptom (n = 79 patients, 74.5%). We identified at least one of the six commonly experienced symptoms in 88 patients (83%). Documentation of the associated severity and distress of these symptoms was inconsistent., Conclusion: Palliative care clinicians routinely documented the co-occurrence of multiple complex symptoms experienced by children and adolescents with cancer. Unstructured progress notes captured evidence of symptom impact on daily life. Clinicians may benefit from a systematic approach to document symptoms in the clinical record which supports symptom identification and communication across clinical teams., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Depression and concussion are highly prevalent neuropsychological disorders that often occur simultaneously. However, due to the high degree of symptom overlap between the two events, including but not limited to headache, sleep disturbances, appetite changes, fatigue, and difficulty concentrating, they may be treated in isolation. Thus, clinical awareness of additive symptom load may be missed. This study measures neuropsychological and electroencephalography (EEG) alpha band coherence differences in collegiate student-athletes with history of comorbid depression and concussion, in comparison to those with a single morbidity and healthy controls (HC). 35 collegiate athletes completed neuropsychological screenings and EEG measures. Participants were grouped by concussion and depression history. Differences in alpha band coherence were calculated using two-way ANOVA with post hoc correction for multiple comparisons. Comorbid participants scored significantly worse on neuropsychological screening, BDI-FS, and PCSS than those with a single morbidity and HC. Two-way ANOVA by group revealed significant main effects of alpha band coherence for concussion, depression, and their interaction term. Post-hoc analysis showed that comorbid participants had more abnormal alpha band coherence than single morbidity, when compared to HC. Comorbidity of concussion and depression increased symptom reporting and revealed more altered alpha band coherence than single morbidity, compared to HC. The abnormalities of the comorbid group exclusively showed decreased alpha band coherence in comparison to healthy controls. The comorbidity of depression and SRC has a compounding effect on depression symptoms, post-concussion symptoms, and brain functional connectivity. This research demonstrates a promising objective measure in comorbid individuals, previously only measured via subjective symptom reporting., 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 © 2024 Elsevier B.V. All rights reserved.)

Introduction: Women with obesity are less likely to participate in mammographic screening and more likely to develop post-menopausal breast cancer. We describe the co-production of a novel training intervention for breast screening staff, targeting obesity-related barriers to participating in a population-based mammographic screening., Methods: A Stakeholder Consultant Group (SCG) was established to guide the co-production process. A narrative review of the literature was conducted, as well as first person interviews of women with lived experience of obesity, to identify/inform themes for service delivery staff training., Results: Three themes from the narrative review emerged: (i) enhanced staff-client communication, (ii) promoting compassionate connections during client interactions (iii) tailored mammography positioning for women with obesity. Iterative co-design and consultation with the SCG resulted in six key sessions delivered within an in-service training day: determinants of obesity, weight stigma and healthcare, screening challenges for women living with obesity, empathy 'mapping', front-line training for reception staff, and screening challenges for radiographers when screening women with obesity. Subsequent practical workshops for radiographers provided hands-on positioning training using a real-life model and a 'mammo vest'. Feedback showed that 74 % of staff rated the training as "very good" or "excellent"., Conclusion: Training to improve staff interactions with women with obesity appears to be acceptable., Implications for Practice: The intervention has been successfully implemented in a population-based breast screening program to improve the mammography experience for both clients and staff. Improving the mammogram experience will improve the likelihood of clients returning to screening when next due. Given the prevalence of obesity and body image issues, targeted interventions that optimize client interactions could significantly reduce breast cancer mortality through early detection., Competing Interests: Conflict of interest statement None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: While clinical practice guidelines (CPGs) for pediatric oncology infection prophylaxis and management exist, few data describe actual management occurring at pediatric oncology centers., Methods: An electronic survey querying infection management practices in nontransplant pediatric oncology patients was iteratively created by the Children's Oncology Group (COG) Cancer Control and Supportive Care Infectious Diseases Subcommittee and sent to leaders at all COG institutions, limiting each site to one response to represent their institution., Results: The response rate was 57% (129/227 institutions). Many sites reported utilizing COG-endorsed CPGs for antibacterial (76%) and antifungal prophylaxis (74%), and fever and neutropenia (FN, 64%). Most institutions reported using antimicrobial prophylaxis for patients with acute myeloid leukemia (88% antibacterial, 100% antifungal) and relapsed acute lymphoblastic leukemia (82% antibacterial, 95% antifungal). Definitions of fever, phagocyte recovery, and antibiotic duration in febrile patients varied. Most institutions administer empiric broad-spectrum antibiotics for nonneutropenic fever, although 14% reported withholding antibiotics based on initial clinical status or risk stratification tools. Most respondents reported (70%) admitting FN patients for at least 48 h, however 15% have low-risk FN protocols allowing outpatient management. FN patients remain admitted on antibiotics through count recovery in 50% of institutions, whereas the others employed various early discharge/early antibiotic discontinuation strategies., Conclusions: There is often consistency but also substantial variability in reported antimicrobial prophylaxis strategies and management of patients with fever and represents an opportunity for implementation studies to standardize application of CPG recommendations and randomized trials to advance evidence where knowledge gaps exist., (© 2025 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Most epidemiological studies in pediatric heart failure (HF) use administrative database sources, defining patient cohorts by presence of a single HF ICD code. However, the ability of ICD codes to identify true HF patients is unknown in pediatrics. Here we describe the accuracy of HF ICD-10-CM code search algorithms, in identifying pediatric patients with HF from electronic data sources. Based on the adult HF literature, search algorithms were designed to incorporate HF ICD codes, imaging, and medications. Sensitivity, specificity, positive and negative predictive value and accuracy of the algorithms were tested among children in an advanced HF clinic ("Clinic cohort"). Top-performing algorithms were then tested in a large-scale regional electronic data warehouse (EDW), 01/2017 to 01/2020, generating the "EDW Cohort". False positive cases were identified and characterized by chart review. Within the Clinic Cohort, 78/378 patients (21%) had gold standard HF diagnoses. A search algorithm with one HF ICD coded visit was more sensitive but less specific than > 1 HF ICD coded visit, (sensitivity 94% and specificity 89% versus 69% and 97%, respectively). Correspondingly, > 1 ICD coded visit had a higher PPV than one ICD coded visit; 84% vs. 69%. Accuracy was similar (90% vs 91%). Presence of 1 HF ICD code combined with HF medication had high sensitivity, specificity, PPV, NPV and accuracy, all higher than the single ICD code algorithm. The "1 HF coded visit + any medication" algorithm resulted in highest accuracy (93%). Top-performing algorithms were tested in the EDW: the algorithm with > 1 HF ICD coded visit, and the algorithm with one HF ICD coded visit combined with HF medication. In the EDW Cohort, 133/248 (53.6%) patients had gold standard HF diagnoses though 115/248 (46.3%) were false positive cases; 41% of those had pulmonary over-circulation from congenital heart disease. Excluding children < 30 days old and those with a history of an isolated VSD repair, complete AVSD repair, or PDA closure further reduced the proportion of false positives to 50/248 (20%). A search algorithm using a single HF ICD code can have acceptable sensitivity, specificity, PPV, NPV and accuracy in identifying children with HF from within electronic medical records. Similar to adult HF literature, specificity improves by including HF medication. When applied to large data sources, however, the search algorithms result in a high proportion of patients with pulmonary overcirculation related to congenital heart disease. To narrow the population to those with myocardial dysfunction, case identification may require use of ICD codes with linked of administrative, surgical, and/or imaging databases., Competing Interests: Declarations Competing Interest The authors declare no competing interests.Ethical ApprovalEthical approval was waived by the local Ethics Committee of University of Utah in view of the retrospective nature of the study., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To better delineate multiplexed gastrointestinal polymerase chain reaction (PCR) panel (MGPP) diagnostic and therapeutic stewardship for patients undergoing treatment for acute leukemia including indications and benefits of testing, optimal timing, and interpretation of results., Study Design: We retrieved all MGPP ordered on 662 consecutive patients admitted with newly diagnosed acute leukemia between June 2015 and May 2024., Setting: Regional referral center for acute leukemia., Results: Fifty-one (17%) of 305 MGPP obtained on the 198 patients who underwent testing identified at least one and 4 (1%) more than one diarrheagenic pathogen. The probability of a positive result was greater if obtained as an outpatient [20/52(38%)], but was not related to type of leukemia, sex, or age. Among the positive results, the pathogens identified included Clostridioides difficile (78% of tests), norovirus (16%), diarrheagenic Escherichia coli (6%), adenovirus 40/41 (4%), and Giardia lamblia (4%). The results of 30 of the 305 tests resulted in a change in treatment (28 C. difficile , 2 G. lamblia ). For the MGPP C. difficile results with an accompanying toxin determination, this included treatment following 16/19 tests with a positive toxin result and 11/19 with a negative. Actionable results other than C. difficile were rarely seen in the inpatient population., Conclusions: MGPP testing is most useful when administered as an outpatient and of little benefit for inpatients with hospital-onset diarrhea. Since MGPP is sensitive and does not distinguish between colonization and causes of diarrhea, caution is needed in interpretation of results, especially for toxin-negative C. difficile .

Context: Social determinants of health including insurance type, income, race, and ethnicity have been shown to influence the utilization of physical therapy and recovery after an orthopedic injury. The influence of social determinants of health on the utilization of physical therapy and recovery from concussion is not well understood., Design: Prospective observational registry study in a specialty concussion program., Methods: Patients diagnosed with a concussion using the Postconcussion Symptom Inventory and the visio-vestibular examination (VVE) who were also referred to physical therapy were included. The main outcomes of interest were the number of days from referral to initial physical therapy evaluation and the number of physical therapy visits completed. Information related to patients' age, race, ethnicity, sex, insurance type, and Child Opportunity Index was extracted from the registry. Multivariate and univariate regressions were used to assess the associations of each sociodemographic characteristic with the outcomes., Results: A total of 341 patients diagnosed with concussion between January 2017 and December 2023 met inclusion criteria. The average age was 14.77, and 64% were female. Patients' age, race, ethnicity, insurance type, and Child Opportunity Index were not associated with days to evaluation or length of care in physical therapy. Higher PCSI scores in children under 12 years (coefficient: 0.17, 95% CI, 0.06-0.29) and female sex (coefficient: 1.2, 95% CI, 0.26-2.1) were associated with a longer course of care in physical therapy. Patients with an abnormal VVE score had on average 2.1 more physical therapy visits than those with a normal VVE score (coefficient: 2.1, 95% CI, 0.73-3.5)., Conclusions: Higher PCSI scores in children, female sex, and higher VVE scores in general predicted a longer course of care in physical therapy. Implementation of a clinical care pathway for concussion care using the PCSI and the VVE may be one strategy to help mitigate systemic factors that might otherwise negatively influence access to physical therapy.

Background: Most epidemiological studies in pediatric heart failure (HF) use administrative database sources, defining patient cohorts by presence of a single HF ICD code. However, the ability of ICD codes to identify true HF patients is unknown in pediatrics. Here we describe the accuracy of HF ICD-10-CM code search algorithms, in identifying pediatric patients with HF from electronic data sources., Methods: Based on the adult HF literature, search algorithms were designed to incorporate HF ICD codes, imaging, and medications. Sensitivity, specificity, positive and negative predictive value and accuracy of the algorithms were tested among children in an advanced HF clinic ("Clinic cohort"). Top-performing algorithms were then tested in a large-scale regional electronic data warehouse (EDW), 01/2017 to 01/2020, generating the "EDW Cohort". False positive cases were identified and characterized by chart review., Results: Within the Clinic Cohort, 78/378 patients (21%) had gold standard HF diagnoses. A search algorithm with one HF ICD coded visit was more sensitive but less specific than >1 HF ICD coded visit, (sensitivity 94% and specificity 89% versus 69% and 97%, respectively). Correspondingly, >1 ICD coded visit had a higher PPV than one ICD coded visit; 84% vs. 69%. Accuracy was similar (90% vs 91%). Presence of 1 HF ICD code combined with HF medication had high sensitivity, specificity, PPV, NPV and accuracy, all higher than the single ICD code algorithm. The "1 HF coded visit + any medication" algorithm resulted in highest accuracy (93%). Top-performing algorithms were tested in the EDW: the algorithm with > 1 HF ICD coded visit, and the algorithm with one HF ICD coded visit combined with HF medication. In the EDW Cohort, 133/248 (53.6%) patients had gold standard HF diagnoses though 115/248 (46.3%) were false positive cases; 41% of those had pulmonary over-circulation from congenital heart disease. Excluding children < 30 days old and those with a history of an isolated VSD repair, complete AVSD repair, or PDA closure further reduced the proportion of false positives to 50/248 (20%)., Conclusions: A search algorithm using a single HF ICD code can have acceptable sensitivity, specificity, PPV, NPV and accuracy in identifying children with HF from within electronic medical records. Similar to adult HF literature, specificity improves by including HF medication. When applied to large data sources, however, the search algorithms result in a high proportion of patients with pulmonary overcirculation related to congenital heart disease. To narrow the population to those with myocardial dysfunction, case identification may require use of ICD codes with linked of administrative, surgical, and/or imaging databases., Competing Interests: Declarations The authors have no relevant financial or non-financial interests to disclose. Ethical approval was waived by the local Ethics Committee of University of Utah in view of the retrospective nature of the study.

Objective: We aimed to validate the Japanese version of the Patient Health Questionnaire-4 (PHQ-4-J). People in Japan, especially healthcare workers (HCWs) suffer from high rates of mental health symptoms. The PHQ-4 is an established ultra-brief mental health measure used in various settings, populations and languages. The Japanese version of the PHQ-4 has not been validated., Methods: Two hundred eighty people in Japan (142 HCWs and 138 from the general public) responded to the PHQ-4-J. Internal consistency, and factorial validity were assessed using confirmatory factor analysis (CFA) and Multiple Indicators Multiple Causes (MIMIC) models., Results: Internal consistency was high (α = 0.70-0.86). CFA yielded very good fit indices for a two-factor solution (RMSEA = 0.04, 95% CI 0.00-0.17) and MIMIC models indicated the performance differed between HCWs and the general population., Conclusions: The PHQ-4-J is a reliable ultra-brief scale for depression and anxiety in Japanese, which can be used to meet current needs in mental health research and practice in Japan. Disaster research and gerontology research can benefit from this scale, enabling mental health assessment with little participant burden. In practice, early detection and personalised care can be facilitated by using the scale. Future research should target specific populations in Japan during a non-emergency time., (© 2024. The Author(s).)

Background: Immune thrombocytopenia (ITP) and Evans syndrome (ES) are manifestations of immune dysregulation. Genetic variants in immune-related genes have been identified in patients with ITP and especially ES. We aimed to explore familial autoimmunity in patients with ITP and ES to understand possible contributions to chronicity., Procedure: We assessed family history in two ways: via patient report for ITP and ES and by population-based analysis using the Utah Population Database (UPDB) for ITP. A total of 266 patients with ITP and 21 patients with ES were identified via chart review, and 252 of the 266 patients with ITP were also identified in the UPDB., Results: Chart review showed familial autoimmunity in 29/182 (15.9%) and 25/84 (29.8%) of patients with newly diagnosed+persistent (nd+p) ITP and chronic ITP (cITP), respectively, (p = .009). The UPDB analysis revealed that autoimmunity in relatives of patients with nd+pITP was higher than in relatives of controls (odds ratio [OR]: 1.69 [1.19-2.41], p = .004), but was not significantly increased in relatives of patients with cITP (OR 1.10 [0.63-1.92], p = .734). Incomplete family history in medical records likely contributed to the observed discrepancy., Conclusions: The findings suggest that familial autoimmunity may have a stronger association with the development of ITP rather than its duration. Twelve (57.1%) patients with ES reported autoimmunity in their relatives. UPDB analysis was omitted due to the small number of patients with ES. The use of population databases offers a unique opportunity to assess familial health and may provide clues about contributors to immune dysregulation features within families., (© 2024 Wiley Periodicals LLC.)

The impact of cold stress on feedlot cattle has received limited investigation in temperate climates. However, cold stress has been found to impact cattle welfare and production in temperate climatic conditions, where ambient temperature (T A ), precipitation, relative humidity (RH), wind speed (WS) and solar radiation (SR) all influencing apparent temperature. While there are many indices to quantify cold stress in cattle, there are limited indices that directly relate to cattle and account for all the interactions between climatic variables. This makes cold stress difficult to quantify, with on-cattle measures such as core body temperature and shivering difficult metrics to obtain in feedlot cattle. Moreover, individual cattle will react differently to cold conditions based on their production, age, sex, coat characteristics (colour and type), breed and nutrition. While cold stress can be difficult to measure, the production status, behavioural and physiological effects of cold stress have been identified, but generally under what could be considered as extreme cold stress events. Similarly, while mitigation strategies such as shelter, bedding and windbreaks have been investigated, limited information is available surrounding their usefulness in temperate climates. Further research is needed to fully investigate the effects of cold stress and how to mitigate those effects in feedlot cattle under conditions, such as those found in Australia., 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 © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To determine whether there is a correlation of genetic diagnosis/result with long-term seizure freedom in pediatric epilepsy patients. Methods: This was a prospective and retrospective cohort study of children with epilepsy referred for genetic testing at a single center. The primary outcomes were presence and type of genetic diagnosis (pathogenic, benign, or variant of uncertain significance) and patient epilepsy status (seizure free, treatment failure, uncertain). Epilepsy gene panels were the primary method of genetic testing. Results: The prospective cohort had 22 patients followed for >11 years and for whom genetic testing was then performed; the retrospective cohort had 78 patients with previous genetic testing followed for >8 years. In the prospective cohort, one patient each of the seizure free or treatment failure groups had a pathogenic genetic variant; mean Combined Annotation Dependent Depletion (CADD) scores 22 and 24, respectively ( P  = .62). In the retrospective cohort, there was no difference in the number of variants ( P  = .97), the variant interpretations ( P  = .29 ClinVar, P  = .39 lab interpretation) or mean CADD scores ( P  = .29) between the seizure-free, treatment failure, and uncertain epilepsy patients. Whole exome and genome sequencing identified pathogenic variants in 70% of patients with treatment failure but were not performed in seizure-free patients. Significance: Our findings show no correlation of the presence or type of epilepsy gene panel result with long-term seizure freedom in pediatric patients. The yield and specificity of pathogenic variants may be higher using whole exome and whole genome sequencing in patients with treatment-resistant epilepsy. Whole exome and whole genome sequencing, or more targeted understanding of specific variants, may be needed to improve the utility of pediatric epilepsy genetic testing., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JLB reports serving on an Advisory Board to Bluebird Bio on an area unrelated to this work. The remaining authors have no conflicts of interest to disclose. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

We present an enhancer AAV toolbox for accessing and perturbing striatal cell types and circuits. Best-in-class vectors were curated for accessing major striatal neuron populations including medium spiny neurons (MSNs), direct and indirect pathway MSNs, as well as Sst-Chodl, Pvalb-Pthlh, and cholinergic interneurons. Specificity was evaluated by multiple modes of molecular validation, three different routes of virus delivery, and with diverse transgene cargos. Importantly, we provide detailed information necessary to achieve reliable cell type specific labeling under different experimental contexts. We demonstrate direct pathway circuit-selective optogenetic perturbation of behavior and multiplex labeling of striatal interneuron types for targeted analysis of cellular features. Lastly, we show conserved in vivo activity for exemplary MSN enhancers in rat and macaque. This collection of striatal enhancer AAVs offers greater versatility compared to available transgenic lines and can readily be applied for cell type and circuit studies in diverse mammalian species beyond the mouse model., Competing Interests: Declaration of interests Authors JTT, BPL, EL, TLD, BTa, HZ, JKM are co-inventors on patent application PCT/US2021/45995 Artificial expression constructs for selectively modulating gene expression in striatal neurons. Authors JTT, BPL, TLD, BTa, TEB are co-inventors on provisional patent application US 63/582,759 Artificial expression constructs for modulating gene expression in the basal ganglia. HZ – is on the Scientific Advisory Board of MapLight Therapeutics, Palo Alto, CA

To understand the neural basis of behavior, it is essential to measure spiking dynamics across many interacting brain regions. Although new technologies, such as Neuropixels probes, facilitate multi-regional recordings, significant surgical and procedural hurdles remain for these experiments to achieve their full potential. Here, we describe skull-shaped hemispheric implants enabling large-scale electrophysiology datasets (SHIELD). These 3D-printed skull-replacement implants feature customizable insertion holes, allowing dozens of cortical and subcortical structures to be recorded in a single mouse using repeated multi-probe insertions over many days. We demonstrate the procedure's high success rate, biocompatibility, lack of adverse effects on behavior, and compatibility with imaging and optogenetics. To showcase SHIELD's scientific utility, we use multi-probe recordings to reveal novel insights into how alpha rhythms organize spiking activity across visual and sensorimotor networks. Overall, this method enables powerful, large-scale electrophysiological experiments for the study of distributed neural computation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Children, adolescents, and young adults (CAYAs) with Down syndrome (DS) and hematologic malignancies are particularly vulnerable to infections and related complications. There are limited data regarding COVID-19 infections in this group. We aimed to understand the clinical course of COVID-19 in this population., Methods: This observational study leverages the de-identified clinical and sociodemographic data captured by the Pediatric Oncology COVID-19 Case Report Registry (POCC) regarding CAYAs with cancer and COVID-19. We evaluated CAYAs (≤21 years at COVID-19 infection) with hematologic malignancies and COVID-19 reported from April 1, 2020 to May 2, 2023, comparing those with and without DS. Using multivariable logistic regression, we examined rates of hospitalization, intensive care unit (ICU) admission, respiratory support, and changes in cancer-directed therapy., Results: Among 1408 CAYAs with hematologic malignancies, 55 had DS (CAYA-DS). CAYA-DS had higher rates of hospitalization, ICU admission, and respiratory support (p < .001) than CAYAs without DS. Similarly, multivariable analyses found higher odds of hospitalization (odds ratio [OR] = 2.8, 95% confidence interval [CI]: 1.5-5.1), ICU admission (OR = 4.2, 95% CI: 1.9-9.1), and need for respiratory support (OR = 4.2, 95% CI: 2.0-8.8) among CAYA-DS. Modifications to cancer-directed therapy were more common among CAYA-DS when related to neutropenia (p = .001), but not when unrelated to neutropenia (p = .88); CAYA-DS did not have higher odds of changes to cancer-directed therapy (OR = 1.20, 95% CI: 0.7-2.1)., Conclusions: We identify CAYA-DS with hematologic malignancies as a vulnerable subpopulation at greater risk for severe COVID-19 infection. This can inform conversations with patients and families regarding therapeutic and preventive measures, as well as the risks and benefits of modifying chemotherapy in the setting of COVID-19., (© 2024 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Background: Mammographic breast screening/rescreening rates are suboptimal for women with obesity and/or physical disabilities. This study describes development of an intervention framework targeting obesity- and disability-related barriers to improve participation., Methods: Mixed methods combined a systematic review with first-person perspectives to optimise screening engagement among women with obesity and/or physical disabilities. Phase 1 (systematic review) was conducted following the PRISMA framework. Phase 2 involved in-depth interviews with n = 8 women with lived experience of obesity and/or physical disabilities. An inductive coding approach was applied to the data which was then combined with Phase 1 results to develop the intervention framework., Results: Six studies were included in the systematic review. Tailored education based on individual risk increased willingness to undergo mammographic screening. Recommendations to improve the screening experience included partnerships with consumers, targeted messaging, and enhanced professional development for breast screening staff. Participants also identified strategies to improve the uptake of screening and the experience itself., Conclusion: Development and evaluation of interventions informed by frameworks like the one developed in this study are needed to improve engagement in screening to promote regular participation among women with physical disabilities and/or obesity., Implications for Practice: Successful implementation of practice interventions co-designed by women with obesity and/or physical disabilities are likely to improve their breast screening participation. Enhanced training of radiographers aimed at upskilling in empathetic communication around required manoeuvring and potentially longer screening times for clients with obesity and/or physical disabilities may encourage more positive client practitioner interactions. Client information aimed at women with obesity should include information on how to prepare for the appointment and explain there may be equipment limitations compromising imaging which may not be completed at an initial appointment., (Copyright © 2024. Published by Elsevier Ltd.)

Purpose: The optimal management of fever without severe neutropenia (absolute neutrophil count [ANC] ≥500/µL) in pediatric patients with cancer is undefined. The previously proposed Esbenshade Vanderbilt (EsVan) models accurately predict bacterial bloodstream infections (BSIs) in this population and provide risk stratification to aid management, but have lacked prospective external validation., Materials and Methods: Episodes of fever with a central venous catheter and ANC ≥500/µL occurring in pediatric patients with cancer were prospectively collected from 18 academic medical centers. Variables included in the EsVan models and 7-day clinical outcomes were collected. Five versions of the EsVan models were applied to the data with calculation of C-statistics for both overall BSI rate and high-risk organism BSI (gram-negative and Staphylococcus aureus BSI), as well as model calibration., Results: In 2,565 evaluable episodes, the BSI rate was 4.7% (N = 120). Complications for the whole cohort were rare, with 1.1% (N = 27) needing intensive care unit (ICU) care by 7 days, and the all-cause mortality rate was 0.2% (N = 5), with only one potential infection-related death. C-statistics ranged from 0.775 to 0.789 for predicting overall BSI, with improved accuracy in predicting high-risk organism BSI (C-statistic 0.800-0.819). Initial empiric antibiotics were withheld in 14.9% of episodes, with no deaths or ICU admissions attributable to not receiving empiric antibiotics., Conclusion: The EsVan models, especially EsVan2b, perform very well prospectively across multiple academic medical centers and accurately stratify risk of BSI in episodes of non-neutropenic fever in pediatric patients with cancer. Implementation of routine screening with risk-stratified management for non-neutropenic fever in pediatric patients with cancer could safely reduce unnecessary antibiotic use.

Mg-S batteries hold great promise as a potential alternative to Li-based technologies. Their further development hinges on solving a few key challenges, including the lower capacity and poorer cycling performance when compared to Li counterparts. At the heart of the issues is the lack of knowledge on polysulfide chemical behaviors in the Mg-S battery environment. In this Review, a comprehensive overview of the current understanding of polysulfide behaviors in Mg-S batteries is provided. First, a systematic summary of experimental and computational techniques for polysulfide characterization is provided. Next, conversion pathways for Mg polysulfide species within the battery environment are discussed, highlighting the important role of polysulfide solubility in determining reaction kinetics and overall battery performance. The focus then shifts to the negative effects of polysulfide shuttling on Mg-S batteries. The authors outline various strategies for achieving an optimal balance between polysulfide solubility and shuttling, including the use of electrolyte additives, polysulfide-trapping materials, and dual-functional catalysts. Based on the current understanding, the directions for further advancing knowledge of Mg polysulfide chemistry are identified, emphasizing the integration of experiment with computation as a powerful approach to accelerate the development of Mg-S battery technology., (© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

Competing Interests: Declaration of competing interest J.L.B. has provided services a consultant for Neurogene, Passage Bio, and Ionis; is in a clinical trial with SwanBio and Calico; receives grant funding from NIH; writes content for UpToDate; has stock in Orchard; and receives royalties from Manson Publishing and BioFire. The other authors report no competing interests.

Purpose: Function and cosmesis may be improved by replantation following digital amputation in pediatric patients. However, accurate failure and complication rate estimates may be limited as most pertinent studies reflect single center/surgeon experience and therefore are limited by small sample sizes. The primary aim of this study was to assess the rate of failure (amputation) following pediatric digital replantation. Secondary aims include evaluating the rate of complications and associated resource utilization (intensive care unit stays, readmission rate, and hospital length of stay)., Methods: Digital replantation patients were identified from 47 pediatric hospitals using the 2004 to 2020 Pediatric Health Information System nationwide database. Using applicable International Classification of Disease 9/10 and Current Procedural Terminology codes, we identified complications after replantation, including revision amputation, infection, surgical complications, medical complications, admission to intensive care unit (ICU), and length of stay., Results: Of the 348 patients who underwent replantation the mean age was 8.3 ± 5.1 years, and 27% were female. Mean hospital length of stay was 5.8 ± 4.7 (range, 1-28) days. Of the 53% of patients who required ICU admission, the mean ICU length of stay was 2.4 ± 3.3 days. Failure/amputation after replantation occurred in 71 (20.4%) patients, at a mean of 9.7 ± 27.2 days postoperatively. Surgical complications occurred in 58 (17%) patients, 30-day hospital readmissions occurred in 5.7% of patients, and 90-day readmissions occurred in 6.3% patients., Conclusion: The estimated rate of failure following pediatric digit replantation was 20%. Our data on failure and complication rates and associated resource utilization may be useful in counseling pediatric replantation patients and their families and provide an update on prior literature., Level of Evidence: IV, Prognosis.

Unfractionated heparin (UFH) is a commonly used anticoagulant for pediatric patients undergoing extracorporeal membrane oxygenation (ECMO), but evidence is lacking on the ideal dosing. We aimed to (1) develop a population pharmacokinetic (PK) model for UFH, measured through anti-factor Xa assay; (2) optimize UFH starting infusions and dose titrations through simulations; and (3) explore UFH exposure-clinical outcomes relationship. Data from 218 patients admitted to Utah's Primary Children's Hospital were retrospectively collected. A 1-compartment PK model with time-varying clearance (CL) adequately described UFH PK. Weight on CL and volume of distribution and ECMO circuit change on CL were significant covariates. The typical estimates for initial CL and first-order rate constant to reach steady-state CL were 0.57 L/(h·10 kg) and 0.02/h. Comparable to non-ECMO patients, the typical steady-state CL was 0.81 L/(h·10 kg). Simulations showed that a 75 IU/kg UFH bolus dose followed by starting infusions of 25 and 20 IU/h/kg for patients aged younger than 6 years and 6 years or older, respectively, achieved the therapeutic target in 56.6% of all patients, whereas only 3.1% exceeded the target. The proposed UFH titration schemes achieved the target in more than 90% of patients while less than 0.63% were above the target after 24 and 48 hours of treatment. The median intensive care unit survival time in patients within and below the target at 24 hours was 136 and 66 hours, respectively. In conclusion, PK model of UFH was developed for pediatric patients on ECMO. The proposed UFH dosing scheme attained the anti-factor Xa target rapidly and safely., (© 2023, The American College of Clinical Pharmacology.)

Mid-systolic notching (MSN) of the pulmonary valve Doppler signal represents a reflected systolic pressure wave from the pulmonary vasculature and is often seen in pulmonary hypertension (PH). We hypothesize that MSN is associated with a higher pulmonary vascular resistance (PVR) and mean pulmonary artery pressure (mPAP), and a diagnosis of PH in pediatric patients. This was a retrospective study of patients ≤ 18 years who had an echocardiogram obtained ≤ 30 days before catheterization for suspected PH. MSN was defined as an indentation in the initial two thirds of the systolic Doppler signal. PH was defined as mPAP > 20 mmHg and PVR ≥ 3.0 Wu  m 2 . Subgroups (MSN vs. normal) were compared. Receiver operator characteristic determined a continuous variable's discriminatory ability for a diagnosis of PH. Reproducibility of MSN was assessed. In total, 90 patients (73 with congenital heart disease) were included, of which 36 had MSN and 54 were normal. MSN patients were more likely to have PH, and had significantly higher mPAP, PVR, and lower pulmonary stroke volume. The presence of MSN had good discriminatory ability for PH diagnosis. The presence of MSN had high specificity (96%) for PH, whereas sensitivity was lower (54%). Reproducibility was 100% for MSN. MSN is a simple, highly reproducible echocardiographic metric associated with higher mPAP and PVR. When present, there is a high likelihood a diagnosis of PH confirmed by catheterization. Incorporation of MSN into imaging protocols may be useful. MSN appears worthy of further investigation in pediatric patients with suspected PH., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Problems associated with muddy pens have been identified as some of the most serious animal welfare issues related to outdoor feedlot beef production, but there is relatively little work examining the use of woodchip bedding for lot-fed beef cattle under conditions of cold, wet, but non-freezing winters on soil under-bases. This study examined the effects of graded levels of woodchip on the performance and behaviour of feedlot cattle housed in wet pen conditions. Bos taurus steers (n = 300; 379.1 ± 24.1 kg) were blocked by weight and breed and randomly assigned to 30 10-steer feedlot pens provided with either no woodchip bedding (Control, n = 10) manure interface only, or 15 cm depth of woodchip bedding (W15, n = 10) or 30 cm depth of woodchip bedding (W30, n = 10). The steers were housed in these treatment pens for 109 days on a feedlot ration, and the pens were irrigated so that approximately 74 mm of total precipitation (irrigation + natural rainfall) fell onto the pen surface every 30 days. Temperatures were mostly <20 °C maximum and -1 to 5 °C minimum. Steers were weighed on five occasions. Animal position and posture in pen were recorded once a week over an 8-hour day-time period. Carcase characteristics were measured, and adrenal gland weights were recorded. Providing woodchip bedding increased liveweight gain (P < 0.001) and gain:feed (G:F, P = 0.012) after day 28, increased DM intake (DMI) after day 92 (P = 0.049), and increased carcase weight (P = 0.001) and dressing percentage (P = 0.023). There was no additional benefit of W30 over W15 for liveweight gain or DMI, but the benefit of W15 for G:F was lower than that of W30 by the end of the feeding period (P = 0.012). There were no effects of bedding on other carcase quality traits. Steers in Control pens utilised the front of the pen for lying and standing more than the W15 and W30 steers (P < 0.001) suggesting the steers in the Control pens perceived the front of the pen as less aversive, potentially due to increased drainage compared to rest of the pen and proximity to feed bunk. Adrenal gland weight/kg and carcase weight tended to be higher in the Control treatment group than the W30 steers (P = 0.077). This research has demonstrated that for a 109-day feeding period in cold, wet conditions, steer performance and welfare can be improved by providing a minimum of 15 cm woodchip bedding., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Neurovascular decoupling is a common consequence after brain injuries like sports-related concussion. Failure to appropriately match cerebral blood flow (CBF) with increases in metabolic demands of the brain can lead to alterations in neurological function and symptom presentation. Therapeutic hypothermia has been used in medicine for neuroprotection and has been shown to improve outcome. This study aimed to examine the real time effect of selective head cooling on healthy controls and concussed athletes via magnetic resonance spectroscopy (MRS) and arterial spin labeling (ASL) measures., Methods: 24 participants (12 controls; 12 concussed) underwent study procedures including the Post-Concussion Symptom Severity (PCSS) Rating Form and an MRI cooling protocol (pre-cooling (T1 MPRAGE, ASL, single volume spectroscopy (SVS)); during cooling (ASL, SVS))., Results: Results showed general decreases in brain temperature as a function of time for both groups. Repeated measures ANOVA showed a significant main effect of time ( F  = 7.94, p  < 0.001) and group ( F  = 22.21, p  < 0.001) on temperature, but no significant interaction of group and time ( F  = 1.36, p  = 0.237). CBF assessed via ASL was non-significantly lower in concussed individuals at pre-cooling and generalized linear mixed model analyses demonstrated a significant main effect of time for the occipital left ROI ( F  = 11.29, p  = 0.002) and occipital right ROI ( F  = 13.39, p  = 0.001). There was no relationship between any MRI metric and PCSS symptom burden., Discussion: These findings suggest the feasibility of MRS thermometry to monitor alterations of brain temperature in concussed athletes and that metabolic responses in response to cooling after concussion may differ from controls., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Walter, Bai, Wilkes, Neuberger, Sebastianelli and Slobounov.)

Background: Soft tissue sarcomas are rare and often go undetected until a later stage, particularly when they present as intra-articular or tenosynovial lesions mimicking benign synovial pathologies. The failure to distinguish between malignant and benign synovial disease can have a significant impact on patient outcomes and limit alternatives for local control surgery and limb salvage., Case Description: In this case series, we present two cases of soft tissue sarcomas, one being an intraarticular synovial chondrosarcoma, and the other a pleomorphic spindle cell sarcoma centred along tendon sheaths. Radiologically, the initial clinical presentation of these cases resembled benign synovial pathologies, leading to a delay in diagnosis and treatment., Conclusion: Our study underscores the importance of maintaining a low threshold of suspicion for surveillance, a multidisciplinary approach, and early histological diagnosis to ensure appropriate timely treatment and a favourable prognosis for patients with soft tissue sarcomas., Competing Interests: The authors declare no conflict of interest., (© 2023 The Mediterranean Journal of Rheumatology (MJR).)

When sensory information is incomplete or ambiguous, the brain relies on prior expectations to infer perceptual objects. Despite the centrality of this process to perception, the neural mechanism of sensory inference is not known. Illusory contours (ICs) are key tools to study sensory inference because they contain edges or objects that are implied only by their spatial context. Using cellular resolution, mesoscale two-photon calcium imaging and multi-Neuropixels recordings in the mouse visual cortex, we identified a sparse subset of neurons in the primary visual cortex (V1) and higher visual areas that respond emergently to ICs. We found that these highly selective 'IC-encoders' mediate the neural representation of IC inference. Strikingly, selective activation of these neurons using two-photon holographic optogenetics was sufficient to recreate IC representation in the rest of the V1 network, in the absence of any visual stimulus. This outlines a model in which primary sensory cortex facilitates sensory inference by selectively strengthening input patterns that match prior expectations through local, recurrent circuitry. Our data thus suggest a clear computational purpose for recurrence in the generation of holistic percepts under sensory ambiguity. More generally, selective reinforcement of top-down predictions by pattern-completing recurrent circuits in lower sensory cortices may constitute a key step in sensory inference.

Objectives: Approximately 40% of boys with X-linked adrenoleukodystrophy (ALD) develop inflammatory demyelinating brain lesions (cerebral ALD, cALD) and are at risk for death or severe disability. Risk factors for cALD are poorly understood. Our objective was to evaluate whether vitamin D status, which influences immune function, is associated with risk for cALD., Methods: We used two independent cohorts to assess whether low vitamin D status is correlated with cALD. We used complementary proxies for vitamin D status: plasma 25-hydroxyvitamin D levels and latitude. In our first cohort, we measured 25-hydroxyvitamin D in biobanked plasma samples from ALD boys with initially normal brain MRIs followed at two expert centers. In a second cohort, we measured latitude (using home ZIP code) among ALD boys identified in a national administrative database (PHIS) covering 51 US pediatric hospitals. We used logistic regression models to estimate the odds of developing cALD in each cohort., Results: In the first cohort, we identified 20 ALD boys with a total of 53 plasma sample timepoints who met inclusion criteria; 50% ( n = 10) subsequently developed cALD. Average 25-hydroxyvitamin D levels were lower among boys who developed cALD than those who did not (median 28.9 vs 36.6 ng/ml); p = 0.019. For each 10 ng/mL decrease in 25-hydroxyvitamin D, the odds ratio for developing cALD was 6.94; p = 0.044. In the second cohort, we identified 230 ALD boys across 28 states; 57% of boys ( n = 132) developed cALD. Each 2° increase in latitude conferred an odds ratio of 1.17 (95% confidence interval, 1.01, 1.35); p = 0.036 for developing cALD., Conclusions: Using independent cohorts, we found that ALD boys with lower pre-morbid plasma levels of 25-hydroxyvitamin D, or more northerly latitude of residence, were more likely to develop cALD. These findings offer complementary lines of evidence that vitamin D and/or ultraviolet light exposure influence cALD risk., Competing Interests: All authors have completed the ICMJE uniform disclosure form and declare that the study described in the submitted work was supported, in part, by the Child Neurology Foundation Scientific Award and NIH/NINDS K23NS087151; KV has received research grants from Bluebird bio and Minoryx for clinical trials in ALD participants, separate from the submitted work; consulting fees from bluebird bio, Minoryx, Viking Therapeutics, Poxel, and Orpheris for ALD therapy development separate from the submitted work. He participates in advisory boards for Poxel (paid), Viking (paid), ALD Connect (unpaid), and the United Leukodystrophy Foundation (unpaid). GVR has received consulting fees from bluebird bio, from Viking Therapeutics, and for therapy development outside the submitted work. JLB has received research support from Sanofi and Autobahn as well as consulting fees from Neurogene, Passage Bio, Takeda, and Autobahn all for work outside the submitted work. He is an unpaid board member at ALD Connect and wFluidx. No other relationships or activities that could appear to have influenced the submitted work., (© 2023 The Authors. Annals of the Child Neurology Society published by Wiley Periodicals LLC on behalf of the Child Neurology Society.)

Background: Anomalous aortic origin of the left coronary artery (AAOLCA) confers a rare, but significant, risk of sudden cardiac death in children. Surgery is recommended for interarterial AAOLCA, and other subtypes considered benign. We aimed to determine the clinical characteristics and outcomes of 3 AAOLCA subtypes., Methods: All patients with AAOLCA <21 years old were prospectively enrolled (December 2012-November 2020), including group 1: AAOLCA from the right aortic sinus with interarterial course, group 2: AAOLCA from the right aortic sinus with intraseptal course, and group 3: AAOLCA with a juxtacommissural origin between the left and noncoronary aortic sinus. Anatomic details were assessed using computed tomography angiography. Provocative stress testing (exercise stress testing and stress perfusion imaging) was performed in patients >8 years old or younger if concerning symptoms. Surgery was recommended for group 1 and in select cases in group 2 and group 3., Results: We enrolled 56 patients (64% males) with AAOLCA (group 1, 27; group 2, 20; group 3, 9) at median age of 12 years (interquartile range, 6-15). Intramural course was common in group 1 (93%) compared with group 3 (56%) and group 2 (10%). Seven (13%) presented with aborted sudden cardiac death (group 1, 6/27; group 3, 1/9); 1 (group 3) with cardiogenic shock. Fourteen/42 (33%) had inducible ischemia on provocative testing (group 1, 32%; group 2, 38%; group 3, 29%). Surgery was recommended in 31/56 (56%) patients (group 1, 93%; group 2, 10%; and group 3, 44%). Surgery was performed in 25 patients at a median age 12 (interquartile range, 7-15) years; all have been asymptomatic and free from exercise restrictions at median follow-up of 4 (interquartile range, 1.4-6.3) years., Conclusions: Inducible ischemia was noted in all 3 AAOLCA subtypes while most aborted sudden cardiac deaths occurred in interarterial AAOLCA (group 1). Aborted sudden cardiac death and cardiogenic shock may occur in AAOLCA with left/nonjuxtacommissural origin and intramural course, thus also deemed high-risk. A systematic approach is essential to adequately risk stratify this population., Competing Interests: Disclosures None.

Introduction: Chondrosarcoma of the synovium is a rare and malignant form of cartilaginous tumor that originates in synovial tissue. There have only been a limited number of reported cases of malignant transformation of synovial chondromatosis (SC) into secondary chondrosarcoma (SCH), primarily in the hip and knee, in patients with resistant illness. The occurrence of chondrosarcoma in SC of the wrist is highly uncommon, as evidenced by only a single previous case study that has been documented in the literature., Case Report: This study presents a case series of two patients with primary SC who developed SCH at the wrist joint., Conclusion: Clinicians treating localized swellings of the hand and wrist should be alert to the likelihood of a sarcoma diagnosis to minimize delays to definitive therapy., (Copyright: © Indian Orthopaedic Research Group.)

Thyroid mucoepidermoid carcinoma (MEC) is a rare thyroid malignancy first documented in 1977. The majority of thyroid MECs are indolent, low-grade tumours with excellent prognosis. A woman in her 60s presented with an ongoing sensation of a lump in the left neck. There were no swallowing, voice or airway concerns. Ultrasound of the neck showed an enlarged thyroid with U5 and U3 features on the right and left lobes, respectively. Right fine needle aspiration cytology (FNAC) demonstrated certain features of Hurthle cell or anaplastic carcinoma (Thy5). Left FNAC showed Hurthle cell changes with atypical cells and prominent nucleoli (Thy3a). Following total thyroidectomy, histopathology revealed synchronous right low-grade MEC and left papillary thyroid microcarcinomas (pT2(m) N0 M0) on a background of Hashimoto's thyroiditis. This case adds to the literature and details the key histopathological features for a rare but important differential in patients with thyroid carcinoma due to synchronous histological types., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: Previous work has shown that children of Hispanic ethnicity have reduced likelihood to achieve seizure remission, but it was unknown why. The purpose of this study was to evaluate antiseizure medicine (ASM) refill characteristics, comparing Hispanic and non-Hispanic White pediatric patients., Methods: This was a retrospective population-based study in children between ages 6 months and 15 years. Epilepsy outcome was categorized as seizure free, treatment failure, or undetermined. ASM refill characteristics were determined from an insurance provider., Results: 247 patients were identified: 52 (21 %) were treatment failure; 181 (73 %) were seizure free; and 14 (5.7 %) were undetermined. ASM refill rates were similar in Hispanic and White patients (38.2, 32.1, respectively). Hispanic and White patients had similar numbers of different ASMs prescribed (2.1 and 2.4). There was not a significant difference in proportion of days covered between Hispanic and White patients (0.99 and 0.95)., Interpretation: We found no differences between pediatric Hispanic and White epilepsy patients, for number of ASM refills, the number of ASMs prescribed, the choice of ASMs, the proportion of days covered, or the lateness of refills. Our findings suggest that the observation of reduced likelihood to achieve seizure remission in pediatric Hispanic patients is not associated with ASM refill patterns., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The number of Indonesian students in higher education has been increasing rapidly. However, many Indonesian university students report experiencing mental distress. Research on student wellbeing found that self-compassion (i.e., being kind towards oneself in challenging times) and academic engagement (i.e., a commitment and purposeful effort toward study) are essential to students' mental wellbeing. With the present study, we aimed to assess the mental wellbeing of Indonesian students. A convenience sample of 156 Indonesian students completed self-report measures on mental wellbeing, self-compassion and academic engagement (consisting of vigour, dedication and absorption). To contextualise their mental wellbeing, data from Indonesian students were compared with those from 145 UK students using Welch t -tests. Correlation, regression and mediation analyses were then performed to examine the relationships among these variables. Indonesian students had higher levels of self-compassion and absorption and a lower level of dedication than UK students. Self-compassion and academic engagement explained 36% of variance in mental wellbeing. Self-compassion and vigour were identified as significant predictors of mental wellbeing, whereas self-compassion was the strongest predictor. Lastly, vigour did not mediate the pathway from self-compassion to mental wellbeing. Interventions to support self-compassion and academic engagement, especially vigour, in Indonesian students are recommended to support their mental wellbeing.

Objective: To determine differences in long-term health and neurological outcomes following infantile spasms (IS) in patients treated with adrenocorticotropic hormone (ACTH) vs. prednisolone/prednisone (PRED)., Methods: A retrospective, case-control study of patients with an International Classification of Diseases, Ninth Revision, Clinical Modifications (ICD-9) diagnosis of IS, identified over a 10-year period from a national administrative database, was conducted. IS patients treated with ACTH or PRED were determined and cohorts established by propensity score matching. Outcomes, defined by hospital discharge ICD codes, were followed for each patient for 5 years. Related ICD codes were analyzed jointly as phenotype codes (phecodes). Analysis of phecodes between cohorts was performed including phenome-wide association analysis., Results: A total of 5,955 IS patients were identified, and analyses were subsequently performed for 493 propensity score matched patients, each in the ACTH and PRED cohorts. Following Bonferroni correction, no phecode was more common in either cohort ( p < 0.001). However, assuming an a priori difference, one phecode, abnormal findings on study of brain or nervous system (a category of abnormal neurodiagnostic tests), was more common in the PRED cohort ( p <0.05), and was robust to sensitivity analysis. Variability in outcomes was noted between hospitals., Significance: We found that long-term outcomes for IS patients following ACTH or PRED treatment were very similar, including for both neurological and non-neurological outcomes. In the PRED-treated cohort there was a higher incidence of abnormal neurodiagnostic tests, assuming an a priori statistical model. Future studies can evaluate whether variability in outcomes between hospitals may be affected by post-treatment differences in care models., Competing Interests: JW was employed by Intermountain Healthcare. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Baker, Mason, Wilkes, Sant, Sweney and Bonkowsky.)

Objectives: Cerebral X-linked adrenoleukodystrophy (cALD) is an inflammatory demyelination of the brain that can lead to death unless treated by hematopoietic stem cell transplantation. Survival and improved outcomes for cerebral adrenoleukodystrophy are associated with hematopoietic stem cell transplantation at earliest evidence of disease on magnetic resonance imaging (MRI). Our goal was to determine average duration between diagnosis of cALD and hematopoietic stem cell transplantation., Methods: This was a retrospective review of data of patients aged 18 years or younger, using a nationwide administrative health care database (Pediatric Health Information System), with an International Classification of Diseases, Tenth Revision ( ICD-10 ) diagnosis of adrenoleukodystrophy. Time range was October 1, 2015, through June 30, 2021. We determined time to hematopoietic stem cell transplantation by duration between index brain MRI and a code for hematopoietic stem cell transplantation., Results: We identified 27 patients with cerebral adrenoleukodystrophy. Total charges for the cohort was $53 million. Time to transplant averaged 97 days. For Hispanic patients, time to transplant was 117 days, compared with 80 days for White, non-Hispanic patients. Comparison of different hospitals showed significant variability in time to hematopoietic stem cell transplantation., Discussion: We found that time to hematopoietic stem cell transplantation was >3 months for patients with cerebral adrenoleukodystrophy in the hospitals we evaluated. We noted differences in average time by race/ethnicity and by hospital. Our findings suggest opportunity to reduce time to transplant in cerebral adrenoleukodystrophy.

The term 'culture of care' in the context of using animals for scientific purpose describes the culture in organisations that provides support to staff to strive for continuous improvement in:• animal care and welfare;• support and recognition of staff involved in the animal care and use programme;• scientific quality;• openness and transparency.We developed a systematic process for reporting observations and events that have the potential to help with continuous learning, improving animal welfare and supporting staff. The process took learning from the safety, health and environment arena on accident prevention. The two key aspects were (a) the systematic logging of observations and events; and (b) the learning approach to following up on observations. Underpinning our systematic process is the 'Learning from Observations and Events Log'. Reported observations and events can relate to positive practices, general observations as well as near misses.We created an environment to promote continuous improvement for both animals and staff by recognising, rewarding and sharing good practice, as well as where near misses are openly reported and learnt from. Supporting animal welfare, staff welfare, improving scientific quality and transparency are the four key pillars of a positive culture of care.We recognised early on that using a system and learning approach to follow up on observations and events rather than a people and blame approach was key to developing open reporting and a positive culture. In the systems approach, errors are consequences rather than causes, having their origins in systemic factors.

Background: Neuroblastoma is the most common extracranial solid tumor in children. Those with high-risk disease are treated with multimodal therapy, including high-dose chemotherapy, stem cell transplant, radiation, and immunotherapy that have led to multiple long-term complications in survivors. In the late 1990s, consolidation therapy involved myeloablative conditioning including total body irradiation (TBI) with autologous stem cell rescue. Recognizing the significant long-term toxicities of exposure to TBI, more contemporary treatment protocols have removed this from conditioning regimens. This study examines an expanded cohort of 48 high-risk neuroblastoma patients to identify differences in the late effect profiles for those treated with TBI and those treated without TBI., Procedure: Data on the study cohort were collected from clinic charts, provider documentation in the electronic medical record of visits to survivorship clinic, including all subspecialists, and ancillary reports of laboratory and diagnostic tests done as part of risk-based screening at each visit., Results: All 48 survivors of BMT for high-risk neuroblastoma had numerous late effects of therapy, with 73% having between five and 10 late effects. TBI impacted some late effects significantly, including growth hormone deficiency (GHD), bone outcomes, and cataracts., Conclusion: Although high-risk neuroblastoma survivors treated with TBI have significant late effects, those treated without TBI also continue to have significant morbidity related to high-dose chemotherapy and local radiation. A multidisciplinary care team assists in providing comprehensive care to those survivors who are at highest risk for significant late effects., (© 2021 Wiley Periodicals LLC.)

The Japanese construct of ikigai reflects a sense of having 'purpose in life' or a 'reason for living and has been associated with a variety of positive health outcomes. However, to date little research into ikigai exists within Western populations. This study explored the predictive power of ikigai for measures of well-being, depression, and anxiety in an adult Western population. Ninety-four participants (70% female) responded to an online survey. After accounting for the covariates of sex, age, employment status, and student status, multiple hierarchical regression indicated that ikigai positively predicted well-being and negatively predicted depression. While on its own, ikigai negatively predicted anxiety; this was not the case after accounting for the aforementioned covariates. The findings support the importance for investigating ikigai in the West and the need for further exploration of ikigai as a potential means of bringing about benefit in mental well-being., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s) 2022.)

The presence of a genetic condition is a risk factor for increased mortality in hypoplastic left heart syndrome (HLHS). Speckle tracking strain analysis in interstage echocardiograms have shown promise in identifying patients with HLHS at increased risk of mortality. We hypothesized that fetuses with a genetic condition and HLHS have impaired right ventricular global longitudinal strain compared with fetuses with HLHS and no evident genetic condition. We performed a retrospective analysis of 60 patients diagnosed in fetal life with HLHS from 11/2015 to 11/2019. We evaluated presenting echocardiograms and calculated right ventricular global longitudinal strain (RV GLS) and fractional area of change (FAC) using post-processing software. We first compared RV GLS and FAC between those with genetic conditions to those without. We examined the secondary outcome of mortality among those with and without genetic conditions and among HLHS subgroups. Of the 60 patients with available genetic testing, 11 (18%) had an identified genetic condition. Neither RV GLS nor FAC was significantly different between patients with and without genetic conditions. There was no difference in RV GLS or FAC among HLHS phenotype or those who died or survived as infants. However, patients with a genetic syndrome had increased neonatal and overall mortality. In this cohort, RV GLS did not differ between those with and without a genetic diagnosis, among HLHS phenotypes, or between those surviving and dying as infants. Further analysis of strain throughout gestation and after birth could provide insight into the developing heart in fetuses with HLHS., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Reaction time is a common deficit following concussion, making its evaluation critical during return-to-play protocol. Without proper evaluation, an athlete may return-to-play prematurely, putting them at risk of further injury. Although often assessed, we propose that current clinical testing may not be challenging enough to detect lingering deficits. Thus, the aim of this study was to examine reaction time in concussed individuals three times over a 30-day period through the use of a novel reaction time device consisting of simple, complex, and go/no-go reaction time tasks., Methods: Twenty-three concussed subjects completed simple, complex, and go/no-go reaction time tests at three different timepoints: within 7-, 14-, and 30-days of injury, and 21 healthy controls completed the three reaction time tasks during a single session., Results: Independent t-tests revealed that for the simple reaction time task, concussed participants were only significantly slower at session 1 (p = .002) when compared to controls. Complex reaction time task results showed concussed participants to be significantly slower at session 1 (p = .0002), session 2 (p = .001), and session 3 (p = .002). Go/no-go results showed concussed participants to be significantly slower than controls at session 1 (p = .003), session 2 (p = .001), and session 3 (p = .001)., Conclusions: Concussed individuals display prolonged reaction time deficits beyond the acute phase of injury, illustrated using increasingly complex tasks., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Plant parasitic nematodes are a major yield-limiting factor of soybean in the United States and Canada. It has been indicated that soybean cyst nematode (SCN; Heterodera glycines Ichinohe) and reniform nematode (RN; Rotylenchulus reniformis Linford and Oliveira) resistance could be genetically related. For many years, fragmentary data have shown this relationship. This report evaluates RN reproduction on 418 plant introductions (PIs) selected from the U.S. Department of Agriculture Soybean Germplasm Collection with reported SCN resistance. The germplasm was divided into two tests of 214 PIs reported as resistant and 204 PIs reported as moderately resistant to SCN. The defining and reporting of RN resistance changed several times in the last 30 years, causing inconsistencies in RN resistance classification among multiple experiments. Comparison of four RN resistance classification methods was performed: (i) ≤10% as compared with the susceptible check, (ii) using normalized reproduction index (RI) values, and using (iii) transformed data log 10 (x), and (iv) transformed data log 10 (x + 1) in an optimal univariate k-means clustering analysis. The method of transformed data log 10 (x) was selected as the most accurate for classification of RN resistance. Among 418 PIs with reported SCN resistance, the log 10 (x) method grouped 59 PIs (15%) as resistant and 130 PIs (31%) as moderately resistant to RN. Genotyping of a subset of the most resistant PIs to both nematode species revealed their strong correlation with rhg1-a allele. This research identified genotypes with resistance to two nematode species and potential new sources of RN resistance that could be valuable to breeders in developing resistant cultivars.

Mitral valve perforation is an uncommon aetiology of mitral regurgitation in the paediatric population. We present a case where 3-dimensional echocardiography assisted in the diagnosis of the source of mitral regurgitation and the surgical correlation.

Objective: The purpose of our study was to understand the healthcare burden and incidence of Krabbe disease (Krabbe)., Methods: Retrospective analysis of Krabbe patients identified October 1, 2015 through December 31, 2020, ages birth through age 3, evaluated in two national databases. We estimated point prevalence and incidence from year 2016 data., Results: We identified 98 unique Krabbe patients with 736 visits including 260 were inpatient admissions. Total healthcare charges were $51.5 million dollars. We determined a point prevalence of 34 68 Krabbe patients in 2016 ages 0 3 years. This estimates a birth incidence of ~1 in 310,000 live births. Significance: Krabbe disease patients had over $51 million in health care charges and hundreds of hospitalizations. Estimated prevalence and birth incidence is similar to rates observed from newborn screening. Our findings show the tremendous health impacts of Krabbe disease, and provide guidance for efforts in screening and treatment planning.

We aimed to investigate intradialytic changes in ventricular and atrial function using speckle tracking echocardiography (STE) in pediatric hemodialysis (HD). Children with HD vintage > 3 months were enrolled, and echocardiography was performed prior to, during, and after HD. STE was analyzed using GE EchoPAC. Left ventricular (LV) global longitudinal strain (GLS), strain rate (Sr), and mechanical dispersion index (MDI) were calculated as the average from 3 apical views; diastolic strain (Ds) and Sr from 4-chamber tracing; left atrial strain (LAS) and Sr from the 4- and 2-chamber views. A total of 15 patients were enrolled at a median age of 12 years (IQR 8, 16) and median HD vintage of 13 months (IQR 9, 25). GLS worsened during HD (- 15.8 ± 2.2% vs - 19.9 ± 1.9%, p < 0.001). Post-HD GLS was associated with BP decrease (coefficient = 0.62, p = 0.01). LV MDI and systolic Sr did not change. LV Ds progressively worsened (- 8.4% (- 9.2, - 8.0) vs - 11.9% (- 13.4, - 10.3), p < 0.001). LAS changes at mid-HD returned to baseline post-HD. Ds, DSr, LAS, LASr were not associated with BV removal or BP decrease (p > 0.1). In conclusions, intradialytic LV strain and LAS changes consistent with subclinical systolic and diastolic dysfunction were observed during HD in children. Changes in Ds, DSr, LAS, and LASr were not associated with BP change or BV removal and may be related to the disease progression. Longitudinal study using these novel indices may unfold the effect of these subclinical changes on long-term cardiovascular health in children requiring chronic HD., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: The aim of the study was to investigate the association between hospitals' nursing excellence accreditation and patient safety performance-measured by the Hospital-Acquired Conditions Reduction Program (HACRP)., Methods: We linked data from the American Nursing Credentialing Center Magnet Recognition Program, Centers for Medicare and Medicaid Services HACRP, and the American Hospital Association annual survey from 2014 to 2016. We constrained the analysis to hospitals participating in Centers for Medicare and Medicaid Services' HACRP and deployed propensity score matching models to calculate the coefficients for our HACRP patient safety measures. These measures consisted of (a) patient safety indicator 90, (b) hospital-associated infection measures, and (c) total HAC scores. In addition, we used propensity score matching to assess HACRP scores between hospitals achieving Magnet recognition in the past 2 versus longer and within the past 5 years versus longer., Results: Our primary findings indicate that Magnet hospitals have an increased likelihood of experiencing lower patient safety indicator 90 scores, higher catheter-associated urinary tract infection and surgical site infection scores, and no different total HAC scores. Finally, when examining the impact of Magnet tenure, our analysis revealed that there were no differences in Magnet tenure., Conclusions: Results indicate that the processes, procedures, and educational aspects associated with Magnet recognition seem to provide important improvements associated with care that is controlled by nursing practice. However, because these improvements do not differ when comparing total HAC scores nor Magnet hospitals with different tenure, there are likely opportunities for Magnet hospitals to continue process improvements focused on HACRP scores., Competing Interests: The authors disclose no conflict of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To create neonatal reference intervals for the MicroR and HYPO-He complete blood count (CBC) parameters and to test whether these parameters are sensitive early markers of disease at early stages of microcytic/hypochromic disorders while the CBC indices are still normal., Study Design: We retrospectively collected the CBC parameters MicroR and HYPO-He, along with the standard CBC parameters, from infants aged 0-90 days at Intermountain Healthcare hospitals using Sysmex hematology analyzers. We created reference intervals for these parameters by excluding values from neonates with proven microcytic disorders (ie, iron deficiency or alpha thalassemia) from the dataset., Result: From >11 000 CBCs analyzed, we created reference intervals for MicroR and HYPO-He in neonates aged 0-90 days. The upper intervals are considerably higher in neonates than in adults, validating increased anisocytosis and polychromasia among neonates. Overall, 52% of neonates with iron deficiency (defined by reticulocyte hemoglobin equivalent <25 pg) had a MicroR >90% upper interval (relative risk, 4.14; 95% CI, 3.80-4.53; P < .001), and 68% had an HYPO-He >90% upper interval (relative risk, 6.64; 95% CI, 6.03-7.32; P < .001). These 2 new parameters were more sensitive than the red blood cell (RBC) indices (P < .001) in identifying 24 neonates with iron deficiency at birth., Conclusions: We created neonatal reference intervals for MicroR and HYPO-He. Although Sysmex currently designates these as research use only in the US, they can be measured as part of a neonate's CBC with no additional phlebotomy volume or run time and can identify microcytic and hypochromic disorders even when the RBC indices are normal., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Krabbe disease (KD) is a leukodystrophy caused by mutations in the galactosylceramidase gene. Presymptomatic hematopoietic stem cell transplantation (HSCT) is associated with improved outcomes, but most data are from single-center studies. Our objective was to characterize national patterns of HSCT for KD including whether there were disparities in HSCT utilization and outcomes. We conducted a retrospective study of KD patients ≤ age 18 years from November 1, 2015, through December 31, 2019, using the U.S. Children's Hospital Association's Pediatric Health Information System database. We evaluated outcomes for HSCT, intensive care unit days, and mortality, comparing age, sex, race/ethnicity, rural/urban location, and median household income. We identified 91 KD patients. HSCT, performed in 32% of patients, was associated with reduced mortality, 31 vs. 68% without HSCT ( p < 0.003). Trends included the fact that more males than females had HSCT (39 vs. 23%); more Asian and White patients had HSCT compared to Black or Hispanic patients (75, 33, 25, and 17%, respectively); and patients from households with the lowest-income quartile (< $25,000) had more HSCT compared to higher-income quartiles (44 vs. 33, 30, and 0%). Overall, receiving HSCT was associated with reduced mortality. We noted trends in patient groups who received HSCT. Our findings suggest that disparities in receiving HSCT could affect outcomes for KD patients., Competing Interests: JB reports serving as consultant to Bluebird Bio, Calico, Enzyvant, Denali Therapeutics, Neurogene, and Passage Bio, and on the Board of Directors of wFluidx; owning stock in Orchard Therapeutics; receiving royalties from Manson Publishing and from BioMerieux (spouse); and receiving research support from NIH and from the United Leukodystrophy Foundation. There was no role of the funders in design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ghabash, Wilkes and Bonkowsky.)

In order to reduce iron deficiency in neonates at-risk for iron deficiency, we implemented a guideline to increase the consistency of early iron supplementation in infants of diabetic mothers, small for gestational age neonates and very low birthweight premature neonates. Three years following implementation we performed a retrospective analysis in order to assess adherence to the guideline and to compare timing of early iron supplementation and reticulocyte-hemoglobin (RET-He) values at one month of life in at-risk infants. Adherence with early iron supplementation guidelines was 73.4% (399/543) with 51% (275/543) having RET-He values obtained at one month. Despite good adherence, 16% (44/275) had RET-He <25 pg (5th percentile for gestational age). No infants receiving red blood cell transfusion (0/20) had RET-He <25 pg vs. 26.1% (40/153) of those treated with darbepoetin (p < 0.001). There was no evidence of increased feeding intolerance (episodes of emesis/day) with early iron supplementation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To assess the impact of geographic access to surgical center on readmission risk and burden in children after congenital heart surgery., Study Design: Children <6 years old at discharge after congenital heart surgery (Risk Adjustment for Congenital Heart Surgery-1 score 2-6) were identified using Pediatric Health Information System data (46 hospitals, 2004-2015). Residential distance from the surgery center, calculated using ZIP code centroids, was categorized as <15, 15-29, 30-59, 60-119, and ≥120 miles. Rurality was defined using rural-urban commuting area codes. Geographic risk factors for unplanned readmissions to the surgical center and associated burden (total hospital length of stay [LOS], costs, and complications) were analyzed using multivariable regression., Results: Among 59 696 eligible children, 19 355 (32%) had ≥1 unplanned readmission. The median LOS was 9 days (IQR 22) across the entire cohort. In those readmitted, median total costs were $31 559 (IQR $90 176). Distance from the center was inversely related but rurality was positively related to readmission risk. Among those readmitted, increased distance was associated with longer LOS, more complications, and greater costs. Compared with urban patients, highly rural patients were more likely to have an unplanned readmission but had fewer average readmission days., Conclusions: Geographic measures of access differentially affect readmission to the surgery center. Increased distance from the center was associated with fewer unplanned readmissions but more complications. Among those readmitted, the most isolated patients had the greatest readmission costs. Understanding the contribution of geographic access will aid in developing strategies to improve care delivery to this population., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Neurological manifestations are commonly reported in patients with celiac disease (CD). We aimed to characterize epilepsy features in a pediatric population with CD and the effect of a gluten-free diet (GFD) on seizure burden., Methods: A retrospective chart review was performed on pediatric patients treated at the University of Utah and Primary Children's Hospital in Salt Lake City, Utah, with both epilepsy and CD and compared with a control group with epilepsy only., Results: We identified 56 patients with epilepsy and biopsy-confirmed CD (n = 36, 64%) or elevated tissue transglutaminase antibodies (tTG-Ab) without biopsy-confirmed CD (n = 20, 36%). Age- and gender-matched controls were selected from patients with epilepsy only (n = 168). Patients with biopsy-proven CD or positive tTG-Ab had high percentage of drug-resistant epilepsy (DRE) compared with the control group (P < 0.05). Age at seizure onset preceded the diagnosis of CD on average by 5.9 years for patients with DRE (P < 0.01) compared with 2.2 years for those with drug-responsive epilepsy. Adhering to a GFD reduced seizure frequency or resulted in weaning dosage or weaning off of one or more antiseizure medications in a majority of patients with DRE., Conclusions: DRE was more prevalent in pediatric patients with biopsy-confirmed CD and positive tTG-Ab compared with the control group (which included childhood epilepsy syndromes), but comparable with the prevalence of DRE in the general population. Adherence to a GFD in combination with antiseizure medications appears to reduce seizure burden for those with CD and DRE., (Copyright © 2021 Elsevier Inc. All rights reserved.)