Large language models for preventing medication direction errors in online pharmacies.

Errors in pharmacy medication directions, such as incorrect instructions for dosage or frequency, can increase patient safety risk substantially by raising the chances of adverse drug events. This study explores how integrating domain knowledge with large language models (LLMs)-capable of sophisticated text interpretation and generation-can reduce these errors. We introduce MEDIC (medication direction copilot), a system that emulates the reasoning of pharmacists by prioritizing precise communication of core clinical components of a prescription, such as dosage and frequency. It fine-tunes a first-generation LLM using 1,000 expert-annotated and augmented directions from Amazon Pharmacy to extract the core components and assembles them into complete directions using pharmacy logic and safety guardrails. We compared MEDIC against two LLM-based benchmarks: one leveraging 1.5 million medication directions and the other using state-of-the-art LLMs. On 1,200 expert-reviewed prescriptions, the two benchmarks respectively recorded 1.51 (confidence interval (CI) 1.03, 2.31) and 4.38 (CI 3.13, 6.64) times more near-miss events-errors caught and corrected before reaching the patient-than MEDIC. Additionally, we tested MEDIC by deploying within the production system of an online pharmacy, and during this experimental period, it reduced near-miss events by 33% (CI 26%, 40%). This study shows that LLMs, with domain expertise and safeguards, improve the accuracy and efficiency of pharmacy operations.

Child Health Needs and the Developmental-Behavioral Pediatrics Workforce Supply: 2020-2040.

Developmental-behavioral pediatrics (DBP) subspecialists care for children with complex neurodevelopmental and behavioral health conditions; additional roles include education and training, advocacy, and research. In 2023, there were 1.0 DBP subspecialists per 100 000 US children aged 0 to 17 years (range 0.0-3.8), with wide variability in DBP subspecialist distribution. Given the prevalence of DB conditions, the current workforce is markedly inadequate to meet the needs of patients and families. The American Board of Pediatrics Foundation led a modeling project to forecast the US pediatric subspecialty workforce from 2020 to 2040 using current trends in each subspecialty. The model predicts workforce supply at baseline and across alternative scenarios and reports results in headcount (HC) and HC adjusted for percent time spent in clinical care, termed "clinical workforce equivalent." For DBP, the baseline model predicts HC growth nationally (+45%, from 669 to 958), but these extremely low numbers translate to minimal patient care impact. Adjusting for population growth over time, projected HC increases from 0.8 to 1.0 and clinical workforce equivalent from 0.5 to 0.6 DBP subspecialists per 100 000 children aged 0 to 18 years by 2040. Even in the best-case scenario (+12.5% in fellows by 2030 and +7% in time in clinical care), the overall numbers would be minimally affected. These current and forecasted trends should be used to shape much-needed solutions in education, training, practice, policy, and workforce research to increase the DBP workforce and improve overall child health.

Risk of Autoimmune Disease in Research-Identified Cases of Autism Spectrum Disorder: A Longitudinal, Population-Based Birth Cohort Study.

OBJECTIVE: Determine the risk of autoimmune disease in research-identified cases of autism spectrum disorder (ASD) compared with referents using a longitudinal, population-based birth cohort. METHODS: ASD incident cases were identified from a population-based birth cohort of 31,220 individuals. Inclusive ASD definition based on DSM-IV-TR autistic disorder, Asperger syndrome, and pervasive developmental disorder, not otherwise specified, was used to determine ASD cases. For each ASD case, 2 age- and sex-matched referents without ASD were identified. Diagnosis codes assigned between birth and December 2017 were electronically obtained. Individuals were classified as having an autoimmune disorder if they had at least 2 diagnosis codes more than 30 days apart. Cox proportional hazards models were fit to estimate the hazard ratio (HR) between ASD status and autoimmune disorder. RESULTS: Of 1014 ASD cases, 747 (73.7%) were male. Fifty ASD cases and 59 of the 1:2 matched referents were diagnosed with first autoimmune disorder at the median age of 14 and 17.1 years, respectively. ASD cases had increased risk of autoimmune disease compared with matched referents (HR 1.74; 95% confidence interval [CI], 1.21-2.52). The increased risk was statistically significant among male patients (HR 2.01; 95% CI, 1.26-3.21) but not among the smaller number of female subjects (HR 1.38; 95% CI, 0.76-2.50). CONCLUSION: This study provides evidence from a longitudinal, population-based birth cohort for co-occurrence of ASD and autoimmune disorders. Thus, children with ASD should be monitored for symptoms of autoimmune disease and appropriate workup initiated.

Early identification of autism spectrum disorder in children with CHD attending a Cardiac Developmental Outcomes Program.

OBJECTIVE: To determine the prevalence and timing of autism spectrum disorder diagnosis in a cohort of congenital heart disease (CHD) patients receiving neurodevelopmental follow-up and identify associated risk factors. METHOD: Retrospective single-centre observational study of 361 children undergoing surgery for CHD during the first 6 months of life. Data abstracted included age at autism spectrum disorder diagnosis, child and maternal demographics, and medical history. RESULTS: Autism spectrum disorder was present in 9.1% of children with CHD, with a median age at diagnosis of 34 months and 87.9% male. Prematurity, history of post-operative extracorporeal membrane oxygenation, and seizures were higher among those with autism (p = 0.013, p = 0.023, p = 0.001, respectively). Infants with autism spectrum disorder were older at the time of surgery (54 days vs 13.5 days, p = 0.002), and infants with surgery at ≥ 30 days of age had an increased risk of autism spectrum disorder (OR 2.31; 95% CI =1.12, 4.77, p = 0.023). On multivariate logistic regression analysis, being male (OR 4.85, p = 0.005), surgery ≥ 30 days (OR 2.46, p = 0.025), extracorporeal membrane oxygenation (OR 4.91, p = 0.024), and seizures (OR 4.32, p = 0.003) remained associated with increased odds for autism spectrum disorder. Maternal age, race, ethnicity, and surgical complexity were not associated. CONCLUSIONS: Children with CHD in our cohort had more than three times the risk of autism spectrum disorder and were diagnosed at a much earlier age compared to the general population. Several factors (male, surgery at ≥ 30 days, post-operative extracorporeal membrane oxygenation, and seizures) were associated with increased odds of autism. These findings support the importance of offering neurodevelopmental follow-up after cardiac surgery in infancy.

Stepped-Care Cognitive Behavioral Therapy in Children on the Autism Spectrum with Co-occurring Anxiety.

This trial examined stepped-care cognitive-behavioral treatment (CBT) among 96 autistic youth with co-occurring anxiety. Step 1 included an open trial of parent-led, therapist-guided bibliotherapy. Step 2 was family-based CBT for those who did not respond to Step 1 or maintenance for those who did. Eighteen participants (28%) who completed Step 1 responded. Responders reported significantly lower pre-treatment anxiety, internalizing symptoms, and functional impairment than non-responders. After Steps 1 and 2, 80% of completers (55% intent-to-treat) were responders. Anxiety, impairment, and ASD-related impairments significantly improved. Youth in maintenance experienced faster improvement through post-treatment, though there were no group differences at 3-month-follow-up. A stepped approach may help some individuals in Step 1, particularly those who are less anxious.

A Road Map for Academic Developmental-Behavioral Pediatric Practices to Increase Access.

ABSTRACT: There are currently at least 19 million children and adolescents in the United States with disorders of development (learning disorders, attention-deficit/hyperactivity disorder, intellectual disabilities, autism, motor incoordination/cerebral palsy, etc.) and only approximately 800 board-certified developmental-behavioral pediatricians (DBPs) practicing nationally. Given the astronomical mismatch between the number of children and adolescents with developmental disorders and the number of board-certified DBPs, developmental-behavioral pediatric consultations are likely the most inaccessible in all of medicine. With the goal of increasing access to these consultations, an academic developmental-behavioral practice in a large urban hospital system developed a longitudinal "Road Map," led by our team of social workers, which is designed to provide such services while continuing to focus DBP efforts on initial consultative evaluation and diagnosis of as many children as possible. The programs that this new Road Map has provided have allowed the DBP practice not only to increase access to developmental evaluations but also to provide more holistic and targeted care from the point of being added to the waiting list and then throughout the life span at vital transition periods. Especially given the extreme mismatch between the scarce number of practicing DBPs and the prodigious number of pediatric patients with disorders of development, our hope is that other centers will consider replicating this innovative care model to address the ever-growing need for specialized DBP consultation and longitudinal wraparound care for our patients and families.

Patient Satisfaction in Neurodevelopmental Pediatrics: In-Person vs Telemedicine.

BACKGROUND: As a result of the COVID-19 pandemic, medical practices for children with neurodevelopmental disorders urgently adopted telehealth, despite limited data regarding patient satisfaction. OBJECTIVE: To compare patient satisfaction survey scores for neurodevelopmental pediatric appointments completed in-person to appointments completed via telemedicine. METHODS: Using routinely collected Press Ganey survey results, the proportion of Top Box scores (the percentage of responses in the highest possible category [ie, the percentage of "very good" or "always" responses]) for an in-person only group was compared to the proportion in a telemedicine-only group using Fisher's exact test. RESULTS: Most respondents gave Top-Box scores in response to all of the questions for both in-person and telemedicine visits. There were no statistically significant differences in any domain of the Press Ganey surveys in Top Box percentages for in-person vs telemedicine visits. CONCLUSION: This study provides preliminary evidence that telehealth may be an acceptable modality for families seeking care for their children with neurodevelopmental concerns.

Defining Developmental-Behavioral Pediatrics.

There is an insufficient number of specialty developmental-behavioral pediatrics (DBP) physicians, despite nearly 25% of children and adolescents having a developmental, learning, behavioral, or emotional problem. In the nearly 20 years since becoming a board-certified subspecialty, the definition of DBP clinical practice remains somewhat unclear. This lack of clarity likely contributes to recruitment challenges and workforce issues, and limited visibility of DBP among parents, other professionals, payors, and administrators. Defining DBP is therefore an important step in the survival and growth of the field. In this paper, we describe the methodology used to develop this definition along with the origins of DBP, the persistent challenges to defining its scope, what training in DBP involves, and what distinguishes DBP from other overlapping fields of medicine. We propose the following definition of DBP: developmental-behavioral pediatrics (DBP) is a board-certified, medical subspecialty that cares for children with complex and severe DBP problems by recognizing the multifaceted influences on the development and behavior of children and addressing them through systems-based practice and a neurodevelopmental, strength-based approach that optimizes functioning. Developmental behavioral pediatricians care for children from birth through young adulthood along a continuum including those suspected of, at risk for, or known to have developmental and behavioral disorders.

Recalled Experiences of Bullying and Victimization in a Longitudinal, Population-Based Birth Cohort: The Influence of ADHD and Co-Occurring Psychiatric Disorder.

OBJECTIVE: To describe bullying experiences throughout childhood of people with and without childhood ADHD and co-occurring learning and psychiatric disorders from a population-based birth cohort. METHODS: In a secondary data analysis of 199 childhood ADHD cases and 287 non-ADHD referents (N = 486), reported experiences of peer interactions during elementary, middle, or high school were classified as "bully," "victim," "neither," or "both." Associations were assessed with multinomial logistic regression. RESULTS: Adjusted for male sex, the odds of classification as victim-only, victim/bully, or bully- only (vs. neither) were 3.70 (2.36-5.81), 17.71, and 8.17 times higher for childhood ADHD cases compared to non-ADHD referents. Victim-bullies (62.5%) and bullies (64.3%) had both childhood ADHD and other psychiatric disorders versus 38.4% of victims-only and 17.3% of those classified as "neither." CONCLUSION: The list of serious lifetime consequences of having ADHD also includes bullying. We offer future research directions for determining potential causal pathways.

Children With ADHD Are at Risk for a Broad Array of Adverse Adult Outcomes That Cross Functional Domains: Results From a Population-Based Birth Cohort Study.

OBJECTIVE: To identify patterns ("classes") of outcomes for adults with and without childhood ADHD. METHOD: Subjects were 232 childhood ADHD cases and 335 non-ADHD referents from a 1976 to 1982 birth cohort. We used latent class analyses to identify classes based on a broad array of adult psychosocial outcomes and determined the proportion of subjects with childhood ADHD within each class. RESULTS: A three class solution provided optimal model fit; classes were termed "good," "intermediate," and "poor" functioning. Subjects with childhood ADHD comprised 62.8% of the "poor," 53.5% of the "intermediate," and 24.9% of the "good" functioning class. The "poor" functioning class was distinguished by increased likelihood of legal trouble and substance use disorders and included more individuals with childhood ADHD and psychiatric disorder than the "intermediate" class (45.5% vs. 30.6%). CONCLUSION: Children with ADHD are at risk for adverse adult outcomes in multiple domains and co-morbid childhood psychiatric disorders increase risk.

Association Between Exposure of Children to General Anesthesia and Autism Spectrum Disorder.

This study tested the hypothesis that exposure of children prior to their third birthday to procedures requiring general anesthesia is associated with an increased incidence of autism spectrum disorder (ASD) in later life. This study employed a nested, 1:2 matched-case control study design using ASD cases identified in a population-based birth cohort of children born in Olmsted County, MN from 1976 to 2000. Matching variables included sex, date of birth, and mother's age in conditional logistic regression including 499 ASD cases and 998 controls. After adjusting for birth weight and health status, there was no significant association between exposure and ASD (OR 1.27 [95% CI 0.92-1.76]), indicating that general anesthesia is not associated with an increased risk of ASD.

IQ in Autism Spectrum Disorder: A Population-Based Birth Cohort Study.

OBJECTIVES: We aimed to describe the intellectual ability and ratio of boys to girls with average or higher IQ within autism spectrum disorder (ASD) cases identified in a population-based birth cohort. We hypothesized that research-identified individuals with ASD would be more likely to have average or higher IQ, compared to clinically diagnosed ASD. We also hypothesized the male to female ratio would decrease as the definition of ASD broadened. METHODS: ASD incident cases were identified from 31 220 subjects in a population-based birth cohort. Research-defined autism spectrum disorder, inclusive criteria (ASD-RI) was based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, autistic disorder (AD), Asperger Disorder, and pervasive developmental disorder not otherwise specified criteria. Research-defined autism spectrum disorder, narrow criteria (ASD-RN) was a narrower definition based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision AD criteria. Clinical diagnoses of ASD were abstracted from medical and school records. Intellectual ability was based on the last IQ score or on documented diagnoses of intellectual disability if no scores available. Average or higher IQ was defined as IQ ≥86. RESULTS: A total of 59.1% of those with ASD-RI (n = 890), 51.2% of those with ASD-RN (n = 453), and 42.8% of those with clinically diagnosed autism spectrum disorder (n = 187) had average or higher IQ. Within the ASD-RI and ASD-RN groups, boys were more likely than girls to have an average or higher IQ (62.0% vs 51.3% [P = .004] and 54.1% vs. 42.5% [P = .03], respectively). CONCLUSION: Our data suggest that nearly half of individuals with ASD have average or higher IQ. Boys with ASD are more likely to have average or higher IQ than girls. Patients with ASD and higher IQ remain at risk for not being identified.

Understanding Vaccine Hesitancy Among Parents of Children With Autism Spectrum Disorder and Parents of Children With Non-Autism Developmental Delays.

Parents of children with autism spectrum disorder (ASD) may be at greater risk for developing antivaccine beliefs that lead to vaccine delays and/or refusals for their children. We investigated current parental vaccine hesitancy, parents' beliefs about causes of children's developmental delays, and children's vaccination histories among parents of children with ASD or non-ASD developmental delays. Data were analyzed from 89/511 parents (17.4%) who completed the Parent Attitudes About Childhood Vaccines questionnaire and the Revised Illness Perception Questionnaire; 46.1% had childhood vaccination records available. Overall, 21/89 (23.6%, 95% confidence interval [CI]: 15.0-34.0) of parents were vaccine hesitant (ASD n = 19/21 [90.5%], non-ASD n = 2/21 [9.5%]). Parents of children with ASD were significantly more likely to agree with "toxins in vaccines" as a cause of their child's developmental delays (28.4% vs 5.0%, P = .034). The odds of being vaccine hesitant were 11.9 times (95% CI 2.9-48.0) greater among parents who agreed versus disagreed that toxins in vaccines caused their children's developmental delays. Rates of prior vaccine receipt did not differ between hesitant and nonhesitant groups.

The Impact of Asymptomatic Congenital Cytomegalovirus on Adult Quality of Life.

OBJECTIVE: Children born with asymptomatic congenital cytomegalovirus infection (AcCMV) have increased risk for hearing loss, which may affect their quality of life into adulthood. We aim to determine quality of life outcomes among adults who were identified at birth with AcCMV compared with controls, using the cohort of the Houston Congenital CMV Longitudinal Study. METHODS: Quality of life was determined using the self-reported Quality of Life Inventory (QOLI). Sixty-one of 109 AcCMV subjects and 23 of 51 controls completed QOLI. Percentile scores of subjects were compared with percentile scores of controls using Student t tests. QOLI percentile scores were compared among AcCMV subjects with (N = 14) and without hearing loss (N = 47). RESULTS: There was no difference in mean percentile scores on QOLI between AcCMV subjects (59.8 [SD = 27.6]) and controls (57.3 [SD = 35.3]; p = 0.754). Percentile scores indicate an average overall quality of life classification for AcCMV subjects and controls. There was no difference in mean percentile scores on the QOLI between AcCMV subjects with and without hearing loss (54.8 [SD = 25.2]) and 61.3 [SD = 28.3]; p = 0.440, respectively). CONCLUSION: Adults born with AcCMV do not seem to have lower ratings of quality of life compared with uninfected controls. Although our study had small sample size, hearing loss does not seem to be a significant predictor of QOLI percentile scores among AcCMV subjects. Quality of life in adulthood does not seem to be affected by an individual's awareness of screening positive for CMV, which supports the notion of "no harm" occurring from universal newborn screening for congenital CMV infection.

Parent-led, stepped-care cognitive-behavioral therapy for youth with autism and co-occurring anxiety: study rationale and method

Anxiety disorders affect up to 50% of individuals with autism spectrum disorder (ASD) and are significantly impairing to the person affected, as well as to their loved ones. Cognitive-behavioral therapy (CBT) has been established as the gold-standard treatment for anxiety disorders among typically developing youth and adults, and demonstrates similar efficacy among youth with high-functioning autism (HFA). Many CBT interventions utilize a "full-package" treatment approach to treat co-occurring anxiety in youth with ASD. However, these service delivery systems are often therapist-intensive, costly, and impractical, thereby compromising full engagement and treatment adherence. This paper describes the design, rationale, and methodology of a study examining stepped-care CBT for youth with HFA and co-occurring anxiety - a clinical trial examining the efficacy of low-intensity, parent-led CBT as the first line of treatment and utilizing a more intensive, therapist-led intervention for nonresponders. The study will evaluate the potential benefits of stepped-care and parent-led therapist-assisted interventions, predictors of treatment response, and the economic value of using a stepped-care model. Implications for practice will be discussed.

Metasurface Enhanced Sensitized Photon Upconversion: Toward Highly Efficient Low Power Upconversion Applications and Nanoscale E-Field Sensors.

Large-scale nanoimprinted metasurfaces based on silicon photonic crystal slabs were produced and coated with a NaYF4:Yb3+/Er3+ upconversion nanoparticle (UCNP) layer. UCNPs on these metasurfaces yield a more than 500-fold enhanced upconversion emission compared to UCNPs on planar surfaces. It is also demonstrated how the optical response of the UCNPs can be used to estimate the local field energy in the coating layer. Optical simulations using the finite element method validate the experimental results and the calculated spatial three-dimensional field energy distribution helps us to understand the emission enhancement mechanism of the UCNPs closely attached to the metasurface. In addition, we analyzed the spectral shifts of the resonances for uncoated and coated metasurfaces and metasurfaces submerged in water to enable a prediction of the optimum layer thicknesses for different excitation wavelengths, paving the way to applications such as electromagnetic field sensors or bioassays.

Incidence of Celiac Disease in Down Syndrome: A Longitudinal, Population-Based Birth Cohort Study.

American Academy of Pediatrics (AAP) guidelines for children with Down syndrome (DS) include assessment for celiac disease (CD), although data to support this recommendation have been inconsistent. We determined the incidence of CD among children with DS in a population-based birth cohort of children born from 1976 to 2000 in Olmsted County, Minnesota. Individuals with karyotype-confirmed DS and CD (using diagnosis codes, positive serology, and duodenal biopsies) were identified. The incidence of CD in DS was compared with the published incidence of CD for Olmsted County residents (17.4 [95% confidence interval = 15.2-19.6] per 100 000 person-years). Among 45 individuals with DS from the birth cohort, 3 (6.7%) were identified with positive celiac serology and confirmatory biopsies at ages 9, 12, and 23 years, for an incidence of 325 per 100 000 person-years. Thus, individuals with DS have more than 18 times the incidence rate of CD compared with the general population, supporting the AAP guidelines.