Crowdsourcing with Enhanced Data Quality Assurance: An Efficient Approach to Mitigate Resource Scarcity Challenges in Training Large Language Models for Healthcare.

Large Language Models (LLMs) have demonstrated immense potential in artificial intelligence across various domains, including healthcare. However, their efficacy is hindered by the need for high-quality labeled data, which is often expensive and time-consuming to create, particularly in low-resource domains like healthcare. To address these challenges, we propose a crowdsourcing (CS) framework enriched with quality control measures at the pre-, real-time-, and post-data gathering stages. Our study evaluated the effectiveness of enhancing data quality through its impact on LLMs (Bio-BERT) for predicting autism-related symptoms. The results show that real-time quality control improves data quality by 19% compared to pre-quality control. Fine-tuning Bio-BERT using crowdsourced data generally increased recall compared to the Bio-BERT baseline but lowered precision. Our findings highlighted the potential of crowdsourcing and quality control in resource-constrained environments and offered insights into optimizing healthcare LLMs for informed decision-making and improved patient care.

Transparent deep learning to identify autism spectrum disorders (ASD) in EHR using clinical notes.

OBJECTIVE: Machine learning (ML) is increasingly employed to diagnose medical conditions, with algorithms trained to assign a single label using a black-box approach. We created an ML approach using deep learning that generates outcomes that are transparent and in line with clinical, diagnostic rules. We demonstrate our approach for autism spectrum disorders (ASD), a neurodevelopmental condition with increasing prevalence. METHODS: We use unstructured data from the Centers for Disease Control and Prevention (CDC) surveillance records labeled by a CDC-trained clinician with ASD A1-3 and B1-4 criterion labels per sentence and with ASD cases labels per record using Diagnostic and Statistical Manual of Mental Disorders (DSM5) rules. One rule-based and three deep ML algorithms and six ensembles were compared and evaluated using a test set with 6773 sentences (N = 35 cases) set aside in advance. Criterion and case labeling were evaluated for each ML algorithm and ensemble. Case labeling outcomes were compared also with seven traditional tests. RESULTS: Performance for criterion labeling was highest for the hybrid BiLSTM ML model. The best case labeling was achieved by an ensemble of two BiLSTM ML models using a majority vote. It achieved 100% precision (or PPV), 83% recall (or sensitivity), 100% specificity, 91% accuracy, and 0.91 F-measure. A comparison with existing diagnostic tests shows that our best ensemble was more accurate overall. CONCLUSIONS: Transparent ML is achievable even with small datasets. By focusing on intermediate steps, deep ML can provide transparent decisions. By leveraging data redundancies, ML errors at the intermediate level have a low impact on final outcomes.

Intravenous immunoglobulin treatment improves multiple neuropsychiatric outcomes in patients with pediatric acute-onset neuropsychiatric syndrome.

Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) is defined by acute onset of diverse neuropsychiatric manifestations, presumably in the setting of underlying immune dysfunction. We used standardized neuropsychological testing to assess how intravenous immunoglobulins (IVIG) impact neurological and cognitive functions in PANS patients by comparing pretreatment with post-treatment scores. A 5-year retrospective study was undertaken in Children's Postinfectious Autoimmune Encephalopathy Center at University of Arizona. We identified 12 children diagnosed with PANS and treated with immunomodulatory IVIG doses, who also completed neuropsychological testing before and after treatment. We tracked multiple patient characteristics, type/timeline of testing, and number of IVIG courses. Score change of 1 standard deviation in any tested domain/subdomain was considered improvement. We further reviewed records for laboratory signs of triggering infection and immune dysfunction. Improvement occurred in 11/12 patients, in one or multiple domains/subdomains, independently of time between disease onset and IVIG initiation (0-7 years). Participants received 1-7 IVIG courses. Improvement was primarily seen in memory (58%), sensory-motor (37%) and visual-motor integration (30%). In 5/12 patients we detected hypogammaglobulinemia requiring ongoing IVIG replacement, one patient had isolated low IgA. Only one patient had to discontinue IVIG therapy due to severe adverse effects. Standardized neuropsychological testing represents an important tool to objectively measure improvement in PANS patients. IVIG was tolerated well and showed efficacy in the vast majority of participants, independently from timelapse since disease onset, emphasizing impact of immunomodulation in PANS. Significant presence of baseline hypogammaglobulinemia in children with PANS emphasizes the presumed role of immune dysfunction in disease pathogenesis.

Parents' report on the health care management of spina bifida in early childhood.

PURPOSE: This study aimed to describe health care use by type of health providers and care settings visited by children with spina bifida (SB) and to compare this use between children with and without a shunt. METHODS: Health care use data were extracted from a larger study on the health and functioning of children with SB aged 3-6 years. The present study focused on the medical information subsection of a parent-reported survey related to SB care, general care, specialty care (e.g., neurosurgery), emergency care, and complications related to SB and shunts. RESULTS: Parents of 101 children with SB participated. Most of the children were male with myelomeningocele and had a shunt. They visited a health care provider for SB care an average of 7.4 times and a specialist an average of 11.9 times in the previous 12 months. Most visited a multidisciplinary clinic for SB-related care and a private physician's office for general care. Children with a shunt had more SB-related medical visits, more visits to a specialist, and a greater number of different types of specialists than those without it. Frequency of emergency room visits did not differ between the two groups. Health providers informed parents about headaches, vomiting, and fever as signs of complications, and some parents did report shunt-related complications. CONCLUSION: SB is a complex medical condition requiring that children receive medical care from various medical specialists, especially for children with a shunt. Findings on health care use suggest high levels of monitoring and care coordination that parents navigate to care for their child.

Changes in Spina Bifida Lesion Level after Folic Acid Fortification in the US.

OBJECTIVE: To assess whether the severity of cases of spina bifida changed after the institution of mandatory folic acid fortification in the US. STUDY DESIGN: Six active population-based birth defects programs provided data on cases of spina bifida for 1992-1996 (prefortification period) and 1999-2016 (postfortification period). The programs contributed varying years of data. Case information included both a medical record verbatim text description of the spina bifida diagnosis and spina bifida codes (International Classification of Diseases, Clinical Modification, or a modified birth defects surveillance coding system). Comparing the prefortification and postfortification periods, aORs for case severity (upper-level lesions [cervical, thoracic] vs lower-level lesions [lumbar, sacral]) and prevalence ratios (PRs) were estimated. RESULTS: A total of 2593 cases of spina bifida (out of 7 816 062 live births) met the inclusion criteria, including 573 cases from the prefortification period and 2020 cases from the postfortification period. Case severity decreased by 70% (aOR, 0.30; 95% CI, 0.26-0.35) between the fortification periods. The decrease was most pronounced for non-Hispanic White mothers. Overall spina bifida prevalence declined by 23% (PR, 0.77; 95% CI, 0.71-0.85), with similar reductions seen across the early, mid, and recent postfortification periods. A statistically significant decrease in upper-level lesions occurred in the postfortification period compared with the prefortification period (PR, 0.28; 95% CI, 0.22-0.34), whereas the prevalence of lower-level lesions remained relatively similar (PR, 0.94; 95% CI, 0.84-1.05). CONCLUSIONS: The severity of spina bifida cases decreased after mandatory folic acid fortification in the US. Further examination is warranted to better understand the potential effect of folic acid on spina bifida severity.

Intentional interprofessional leadership in maternal and child health.

PURPOSE: This paper aims to describe an interprofessional leadership training program curriculum implemented by a new maternal and child health leadership training program, its collaboration with a well-established leadership consortium, the measures taken to evaluate this training and implications for other leadership programs. DESIGN/METHODOLOGY/APPROACH: The intentional leadership program weaves together the complementary core threads to create strong sets of skills in the areas of personal leadership, leading and influencing others and creating effective interprofessional partnerships with others around women and children's health. FINDINGS: The strong emphasis on the incorporation of leadership competencies coupled with evidence-based leadership training strengthens students' clinical skills, enhances workforce development and increases interdisciplinary health care practices. RESEARCH LIMITATIONS/IMPLICATIONS: The findings presented in this paper are limited to self-reported changes in understanding components of leadership skills for self, others and the wider community and attitudes and beliefs related to interdisciplinary training and interprofessional team decision-making. SOCIAL IMPLICATIONS: The in-depth focus on one's self, teams and on the wider community enhances each individual's grasp of how people and organizations approach women and children's health challenges and strengthens their ability to negotiate among the diverse disciplines and cultures. ORIGINALITY/VALUE: This paper details the intentional incorporation of leadership skill development throughout an academic program and brings to focus the importance of thoughtful leadership development to prepare participants to anticipate, manage and take advantage of changes in knowledge and health care delivery systems.

Postfolate spina bifida lesion level change.

BACKGROUND: Spina bifida accounts for a large proportion of birth defects in the United States. Studies have evaluated the decrease in prevalence at birth after folate fortification of food grains, but little is known about neurologic functional changes related to fortification. This study assesses the functional level of lesions in the prefortification and postfortification eras. METHODS: Data were collected through retrospective review of medical records from a regional multispecialty clinic in Arizona. This study included individuals born between 1981-1995 (prefortification) and 1999-2013 (postfortification). Patients were included if they had a primary diagnosis of spina bifida with or without hydrocephalus. RESULTS: There was a significant difference in functional lesion level with an 85% reduction in thoracic level lesions in the postfortification era (p < .005). There were no differences in gender or ethnicity across eras; however, Hispanic ethnicity had a higher number of cases overall (51.7%). The most common lesion level in both eras was mid-lumbar, accounting for 35.7 and 34.4% of cases in the prefolate and postfolate eras, respectively. CONCLUSIONS: This study demonstrates a significant difference in the distribution of lesion level of spina bifida patients born in the postfortification era, based on neurologic function. Further research with a larger sample size is needed to determine if this observation holds true nationally.

A novel variant in TAF1 affects gene expression and is associated with X-linked TAF1 intellectual disability syndrome.

We investigated the genome of a 5-year-old male who presented with global developmental delay (motor, cognitive, and speech), hypotonia, possibly ataxia, and cerebellar hypoplasia of unknown origin. Whole genome sequencing (WGS) and mRNA sequencing (RNA-seq) were performed on a family having an affected proband, his unaffected parents, and maternal grandfather. To explore the molecular and functional consequences of the variant, we performed cell proliferation assays, quantitative real-time PCR (qRT-PCR) array, immunoblotting, calcium imaging, and neurite outgrowth experiments in SH-SY5Y neuroblastoma cells to compare the properties of the wild-type TATA-box-binding protein factor 1 (TAF1), deletion of TAF1, and TAF1 variant p.Ser1600Gly samples. The whole genome data identified several gene variants. However, the genome sequence data failed to implicate a candidate gene as many of the variants were of unknown significance. By combining genome sequence data with transcriptomic data, a probable candidate variant, p.Ser1600Gly, emerged in TAF1. Moreover, the RNA-seq data revealed a 90:10 extremely skewed X-chromosome inactivation (XCI) in the mother. Our results showed that neuronal ion channel genes were differentially expressed between TAF1 deletion and TAF1 variant p.Ser1600Gly cells, when compared with their respective controls, and that the TAF1 variant may impair neuronal differentiation and cell proliferation. Taken together, our data suggest that this novel variant in TAF1 plays a key role in the development of a recently described X-linked syndrome, TAF1 intellectual disability syndrome, and further extends our knowledge of a potential link between TAF1 deficiency and defects in neuronal cell function.

Understanding the Natural Progression of Spina Bifida: Prospective Study.

BACKGROUND: Spina bifida (SB) is monitored through birth defects surveillance across the United States and in most developed countries. Although much is known about the management of SB and its many comorbid conditions in affected individuals, there are few systematic, longitudinal studies on population-based cohorts of children or adults. The natural history of SB across the life course of persons with this condition is not well documented. Earlier identification of comorbidities and secondary conditions could allow for earlier intervention that might enhance the developmental trajectory for children with SB. OBJECTIVE: The purpose of this project was to assess the development, health, and condition progression by prospectively studying children who were born with SB in Arizona and Utah. In addition, the methodology used to collect the data would be evaluated and revised as appropriate. METHODS: Parents of children with SB aged 3-6 years were eligible to participate in the study, in English or Spanish. The actual recruitment process was closely documented. Data on medical history were collected from medical records; family functioning, child behaviors, self-care, mobility and functioning, and health and well-being from parent reports; and neuropsychological data from testing of the child. RESULTS: In total, 152 individuals with SB were identified as eligible and their parents were contacted by site personnel for enrollment in the study. Of those, 45 (29.6%) declined to participate and 6 (3.9%) consented but did not follow through. Among 101 parents willing to participate, 81 (80.2%) completed the full protocol and 20 (19.8%) completed the partial protocol. Utah enrolled 72.3% (73/101) of participants, predominately non-Hispanic (60/73, 82%) and male (47/73, 64%). Arizona enrolled 56% (28/50) of participants they had permission to contact, predominately Hispanic (18/28, 64%) and male (16/28, 57%). CONCLUSIONS: We observed variance by site for recruitment, due to differences in identification and ascertainment of eligible cases and the required institutional review board processes. Restriction in recruitment and the proportion of minorities likely impacted participation rates in Arizona more than Utah.

Assessment of Cognitive Scales to Examine Memory, Executive Function and Language in Individuals with Down Syndrome: Implications of a 6-month Observational Study.

Down syndrome (DS) is the most commonly identifiable genetic form of intellectual disability. Individuals with DS have considerable deficits in intellectual functioning (i.e., low intellectual quotient, delayed learning and/or impaired language development) and adaptive behavior. Previous pharmacological studies in this population have been limited by a lack of appropriate endpoints that accurately measured change in cognitive and functional abilities. Therefore, the current longitudinal observational study assessed the suitability and reliability of existing cognitive scales to determine which tools would be the most effective in future interventional clinical studies. Subtests of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Cambridge Neuropsychological Test Automated Battery (CANTAB), and Clinical Evaluation of Language Fundamentals-Preschool-2 (CELF-P-2), and the Observer Memory Questionnaire-Parent Form (OMQ-PF), Behavior Rating Inventory of Executive Function®-Preschool Version (BRIEF-P) and Leiter International Performance Scale-Revised were assessed. The results reported here have contributed to the optimization of trial design and endpoint selection for the Phase 2 study of a new selective negative allosteric modulator of the GABAA receptor α5-subtype (Basmisanil), and can be applied to other studies in the DS population.

Incidence of delirium in children with cancer.

There are limited data on the incidence of delirium in children with cancer. We performed a retrospective chart review of all pediatric oncology admissions over a 1 year period to determine the incidence of delirium in this population. We identified seven patients with delirium (10% incidence). Delirium is associated with significant morbidity and mortality, and is likely under-recognized in this population. Improved diagnosis and treatment of delirium may improve outcomes in children with cancer.

Randomized, placebo-controlled, crossover study of methylphenidate for attention-deficit/hyperactivity disorder symptoms in preschoolers with developmental disorders.

OBJECTIVE: The aim of this study was to investigate the short-term efficacy and safety of methylphenidate (MPH) to treat attention-deficit/hyperactivity disorder (ADHD) symptoms in an understudied population of preschoolers with pervasive developmental disorder (PDD) or intellectual disability (ID). METHODS: Fourteen preschoolers with developmental disorders (DD, n = 14; PDD, n = 12; ID, n = 2) underwent MPH titration in a single-blind manner followed by a 4-week double-blind crossover phase. Each child was administered placebo for 2 weeks and "optimal dose" for 2 weeks. The primary outcome measure was the Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition (DSM-IV) ADHD subscale of the Conners' Parent Rating Scale-Revised (CPRS-R-DSM-IV-ADHD). RESULTS: MPH improved parent-rated ADHD symptoms of the preschoolers; 50% were rated as responders. The CPRS-R-DSM-IV-ADHD subscale was significant for the PDD subgroup (p = 0.005, Cohen d = 0.97) and marginally significant for the entire DD sample (p = 0.08, Cohen d = 0.50). Half of the preschoolers experienced side effects with MPH, including reports of increased stereotypic behavior, upset stomach, sleep-related difficulties, and emotional lability. One child discontinued during titration due to side effects. CONCLUSION: The predominant direction of response in these preschoolers with both ADHD and PDD/ID favored MPH, even though the response was more subtle and variable than in older and typically developing children. Due to high rates of adverse effects, preschoolers should be monitored closely.

Prospective, naturalistic, pilot study of open-label atomoxetine treatment in preschool children with attention-deficit/hyperactivity disorder.

OBJECTIVE: The aim of this study was to report preliminary data regarding effectiveness and tolerability of atomoxetine in 3- to 5-year-old preschool children with attention-deficit/hyperactivity disorder (ADHD). METHODS: Nine boys and 3 girls (mean age = 5.0 +/- 0.72 years) diagnosed with ADHD were treated with atomoxetine in an open-label pilot study. Atomoxetine was gradually titrated to a maximum dose of 1.8 mg/kg per day. RESULTS: There was a significant effect of time from baseline to end point on the parent-rated hyperactivity/impulsivity Swanson Nolan and Pelham (SNAP-IV-HI) subscale ratings (F[9, 11] = 6.32, p < 0.0001). The mean difference between the baseline and end-point parent SNAP-IV-HI scores was 10.2 +/- 7.3 (p = 0.0005). The rate of positive response (defined as at least a 30% reduction in the end-point parent SNAP-IV-HI scores and a Clinical Global Impressions-Improvement [CGI-I] rating of Much Improved or Very Much Improved) was 75%. The Children's Global Assessment Scale scores improved significantly over time [F(9, 11) = 6.24 p < 0.001]. The mean end-point daily dose of atomoxetine was 1.59 +/- 0.3 mg/kg. A high proportion (66.7%) of the preschoolers experienced side effects with atomoxetine. Side effects of defiance, tantrums, aggression, and irritability were most disconcerting to parents, and gastrointestinal complaints were the most commonly reported adverse effects. One child was terminated from the study due to "chest ache." There were no changes in weight, height, or cardiovascular measures. CONCLUSION: This open-label pilot study provides preliminary evidence of effectiveness and tolerability of atomoxetine for treating ADHD in preschool children, although double-blind, randomized, placebo-controlled studies are needed to confirm this.

Rehabilitation of children with traumatic brain injury: descriptive analysis of a nationwide sample using the WeeFIM.

OBJECTIVE: To describe functional capability at admission and discharge of children with traumatic brain injury (TBI) in rehabilitation settings. DESIGN: Descriptive analysis. SETTING: Inpatient pediatric rehabilitation hospitals in the United States. PARTICIPANTS: Children (N=3815) in 56 pediatric inpatient rehabilitation facilities who were discharged during 1999 to 2001. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Admission and discharge WeeFIM scores. RESULTS: Admission and discharge WeeFIM scores correlated positively with age at admission, time from injury to rehabilitation admission, and length of stay (LOS). Higher admission WeeFIM scores correlated with shorter LOS, shorter time from injury to admission to rehabilitation, and higher discharge WeeFIM scores. CONCLUSIONS: Children with TBI demonstrated significant improvement in functional measures during rehabilitation. Discharge function and LOS correlated with admission severity, with children who had higher functional status and shorter time between injury and rehabilitation care having higher discharge function and shorter LOS.

Effect of shortened length of stay on functional and educational outcome after pediatric rehabilitation.

OBJECTIVE: The purpose of this study was to assess changes in the length of stay and its effect on effectiveness and return to school in an inpatient pediatric rehabilitation unit during a 5-yr period from fiscal year 1997 through 2001. DESIGN: We reviewed prospectively collected data for a cohort of 321 children during fiscal years 1997-2001. RESULTS: Length of stay was significantly shortened, with mean lengths of stay of 58.9, 43.5, 30.7, 40.9, and 24.0 days in years 1997 through 2001, respectively. Change in length of stay remained significantly decreased after adjusting for age, sex, admission diagnosis, admission severity, and type of health insurance. There was no difference in mean change in effectiveness measured by change in admission and discharge WeeFIM ratings. There were significant differences across years in the educational placement of children at discharge, with a declining trend in the proportion of children discharged to classroom-based educational services. CONCLUSION: There was a reduction in inpatient length of stay during a 5-yr period for children in this pediatric rehabilitation setting. During this time, there was no change in the effectiveness of rehabilitation as measured by functional outcome. However, using return to a classroom setting as a marker of reintegration into routine activities, fewer children returned to a similar level of community participation.

Brain imaging as a predictor of early functional outcome following traumatic brain injury in children, adolescents, and young adults.

OBJECTIVES: A depth of lesion (DOL) model using brain imaging has been proposed to aid in medical decision-making and planning for rehabilitation resource needs. The purpose of this study was to determine the early prognostic value of a DOL classification system for children and young adults following severe traumatic brain injury. METHODS AND OUTCOME MEASURES: CT/MRI brain imaging studies on 92 patients, aged 3 to 21, admitted to the Kluge Children's Rehabilitation Center, University of Virginia, were evaluated to determine DOL. Images were classified according to 5 DOL levels (cortical to brainstem). Functional outcomes in mobility, self-care, and cognition, as rated on the WeeFIM instrument, were compared by DOL levels. RESULTS: Admission WeeFIM scores were significantly different for the DOL levels with the highest score for frontal and/or temporal lesions and the lowest for lesions including the brainstem or cerebellum (P<.001). However, the deeper the lesion, the greater the functional gains (P=.05), resulting in discharge WeeFIM scores that were not significantly different across DOL levels. Patients with deeper lesions tended to have longer lengths of stay in rehabilitation but were able to "catch up" with patients who had more superficial lesions. CONCLUSIONS: While relatively simple and convenient, the DOL classification system is limited in its usefulness as an early prognostic tool. It may not be possible to predict outcome in the early acute phase in the intensive care unit on the basis of standard brain imaging alone. Patients with deeper lesions may enter rehabilitation at a more impaired level but can make remarkable progress, though it may take longer than for less severely injured individuals.