Leveraging a Large Language Model to Assess Quality-of-Care: Monitoring ADHD Medication Side Effects.

Objective: To assess the accuracy of a large language model (LLM) in measuring clinician adherence to practice guidelines for monitoring side effects after prescribing medications for children with attention-deficit/hyperactivity disorder (ADHD). Methods: Retrospective population-based cohort study of electronic health records. Cohort included children aged 6-11 years with ADHD diagnosis and ≥2 ADHD medication encounters (stimulants or non-stimulants prescribed) between 2015-2022 in a community-based primary healthcare network (n=1247). To identify documentation of side effects inquiry, we trained, tested, and deployed an open-source LLM (LLaMA) on all clinical notes from ADHD-related encounters (ADHD diagnosis or ADHD medication prescription), including in-clinic/telehealth and telephone encounters (n=15,593 notes). Model performance was assessed using holdout and deployment test sets, compared to manual chart review. Results: The LLaMA model achieved excellent performance in classifying notes that contain side effects inquiry (sensitivity= 87.2%, specificity=86.3/90.3%, area under curve (AUC)=0.93/0.92 on holdout/deployment test sets). Analyses revealed no model bias in relation to patient age, sex, or insurance. Mean age (SD) at first prescription was 8.8 (1.6) years; patient characteristics were similar across patients with and without documented side effects inquiry. Rates of documented side effects inquiry were lower in telephone encounters than in-clinic/telehealth encounters (51.9% vs. 73.0%, p<0.01). Side effects inquiry was documented in 61% of encounters following stimulant prescriptions and 48% of encounters following non-stimulant prescriptions (p<0.01). Conclusions: Deploying an LLM on a variable set of clinical notes, including telephone notes, offered scalable measurement of quality-of-care and uncovered opportunities to improve psychopharmacological medication management in primary care.

Rapid model-guided design of organ-scale synthetic vasculature for biomanufacturing.

Our ability to produce human-scale bio-manufactured organs is critically limited by the need for vascularization and perfusion. For tissues of variable size and shape, including arbitrarily complex geometries, designing and printing vasculature capable of adequate perfusion has posed a major hurdle. Here, we introduce a model-driven design pipeline combining accelerated optimization methods for fast synthetic vascular tree generation and computational hemodynamics models. We demonstrate rapid generation, simulation, and 3D printing of synthetic vasculature in complex geometries, from small tissue constructs to organ scale networks. We introduce key algorithmic advances that all together accelerate synthetic vascular generation by more than 230 -fold compared to standard methods and enable their use in arbitrarily complex shapes through localized implicit functions. Furthermore, we provide techniques for joining vascular trees into watertight networks suitable for hemodynamic CFD and 3D fabrication. We demonstrate that organ-scale vascular network models can be generated in silico within minutes and can be used to perfuse engineered and anatomic models including a bioreactor, annulus, bi-ventricular heart, and gyrus. We further show that this flexible pipeline can be applied to two common modes of bioprinting with free-form reversible embedding of suspended hydrogels and writing into soft matter. Our synthetic vascular tree generation pipeline enables rapid, scalable vascular model generation and fluid analysis for bio-manufactured tissues necessary for future scale up and production.

Lessons from Developing Multimedia Learning Materials for the Digital Generation.

Recognizing that traditional textbooks on need-driven health technology innovation were increasingly misaligned with the needs of today's undergraduate biomedical engineering students and the faculty who teach them, we initiated an effort to develop new learning materials for this audience. To guide our efforts, we conducted literature searches on best practices in the development of online content and engaging digital learners (primarily Gen-Z). We further held a series of discussions with biomedical engineering students and instructors at universities across the United States. This input led us to the development of a set of modular, online, multimedia learning materials specifically designed for the new generation of undergraduate learners. In this article, we present the key decisions that helped shape the project. We also share the results of feedback surveys and focus groups that shed light on how the materials have been preliminarily received. Finally, we reflect on challenges, opportunities, and lessons from this project that may be helpful to other initiatives focused on the creation of multimedia content for the digital generation.

Anxiety and Depression Treatment in Primary Care Pediatrics.

BACKGROUND AND OBJECTIVES: Primary care pediatricians (PCP) are often called on to manage child and adolescent anxiety and depression. The objective of this study was to describe PCP care practices around prescription of selective serotonin reuptake inhibitors (SSRI) for patients with anxiety and/or depression by using medical record review. METHODS: We identified 1685 patients who had at least 1 visit with a diagnosis of anxiety and/or depression in a large primary care network and were prescribed an SSRI by a network PCP. We randomly selected 110 for chart review. We reviewed the visit when the SSRI was first prescribed (medication visit), immediately previous visit, and immediately subsequent visit. We abstracted rationale for prescribing medication, subspecialist involvement, referral for psychotherapy, and medication monitoring practices. RESULTS: At the medication visit, in 82% (n = 90) of cases, PCPs documented reasons for starting an SSRI, most commonly clinical change (57%, n = 63). Thirty percent (n = 33) of patients had documented involvement of developmental-behavioral pediatrics or psychiatry subspecialists at 1 of the 3 visits reviewed. Thirty-three percent (n = 37) were referred to unspecified psychotherapy; 4% (n = 4) were referred specifically for cognitive behavioral therapy. Of 69 patients with a subsequent visit, 48% (n = 33) had documentation of monitoring for side effects. CONCLUSIONS: When prescribing SSRIs for children with anxiety and/or depression, PCPs in this network documented appropriate indications for starting medication and prescribed without subspecialist involvement. Continuing medical education for PCPs who care for children with these conditions should include information about evidence-based psychotherapy and strategies for monitoring potential side effects.

Large-Scale Production of Wholly Cellular Bioinks via the Optimization of Human Induced Pluripotent Stem Cell Aggregate Culture in Automated Bioreactors.

Combining the sustainable culture of billions of human cells and the bioprinting of wholly cellular bioinks offers a pathway toward organ-scale tissue engineering. Traditional 2D culture methods are not inherently scalable due to cost, space, and handling constraints. Here, the suspension culture of human induced pluripotent stem cell-derived aggregates (hAs) is optimized using an automated 250 mL stirred tank bioreactor system. Cell yield, aggregate morphology, and pluripotency marker expression are maintained over three serial passages in two distinct cell lines. Furthermore, it is demonstrated that the same optimized parameters can be scaled to an automated 1 L stirred tank bioreactor system. This 4-day culture results in a 16.6- to 20.4-fold expansion of cells, generating approximately 4 billion cells per vessel, while maintaining >94% expression of pluripotency markers. The pluripotent aggregates can be subsequently differentiated into derivatives of the three germ layers, including cardiac aggregates, and vascular, cortical and intestinal organoids. Finally, the aggregates are compacted into a wholly cellular bioink for rheological characterization and 3D bioprinting. The printed hAs are subsequently differentiated into neuronal and vascular tissue. This work demonstrates an optimized suspension culture-to-3D bioprinting pipeline that enables a sustainable approach to billion cell-scale organ engineering.

Exercise Capacity and Training Programs in Paediatric Fontan Patients: A Systematic Review.

Background: Exercise training programs can effectively enhance exercise capacity in adults with congenital heart disease, including Fontan patients. However, few studies have explored the impact of exercise training exclusively on paediatric Fontan cohorts. This study systematically reviews exercise capacity in paediatric Fontan patients and the impact of training programs on their cardiovascular health. Methods: Medline and Embase were searched for articles published between January 1990 and November 2021. Studies were included in which data could be analyzed discretely for patients who had undergone the Fontan procedure and were ≤20 years old at the time of study. Cardiopulmonary exercise parameters were extracted from all studies, and training protocols were collected from training programs. Results: The studies demonstrated that Fontan patients exhibit significantly diminished peak exercise capacity relative to healthy peers. We identified 9 training programs that exclusively studied Fontan patients ≤20 years. The programs ranged from 6 weeks to 12 months in duration, with 8 programs incorporating aerobic activity and 1 focused only on inspiratory muscle training. At least 1 measure of maximal or submaximal exercise capacity improved significantly within each program in which statistical analysis was performed, with no reported adverse events. There were 2 additional training programs in which the patients were predominantly (>65%), but not exclusively, Fontan patients. Conclusions: Overall, the results indicate that exercise training programs can safely and effectively improve at least 1 measure of exercise capacity in paediatric Fontan patients.

Contexte: Les programmes d'entraînement peuvent améliorer efficacement la tolérance à l'effort des adultes atteints de cardiopathies congénitales, y compris les patients ayant subi l'intervention de Fontan. Toutefois, peu d'études portant sur l'effet de l'entraînement à l'effort ont été menées exclusivement au sein de cohortes d'enfants ayant subi l'intervention de Fontan. Notre revue systématique porte sur la tolérance à l'effort d'enfants ayant subi l'intervention de Fontan, de même que sur l'effet des programmes d'entraînement sur leur santé cardiovasculaire. Méthodologie: Nous avons effectué des recherches dans MEDLINE et Embase afin de recenser les articles publiés entre janvier 1990 et novembre 2021. Les études retenues comprenaient des données qui pouvaient être l'objet d'une analyse discrète et qui se rapportaient à des patients ayant subi l'intervention de Fontan et étant âgés de 20 ans ou moins lors de leur participation aux études. Nous avons consigné les paramètres d'entraînement cardiopulmonaire de toutes les études, de même que les protocoles des programmes d'entraînement. Résultats: Les études ont démontré que les patients qui ont subi l'intervention de Fontan présentent une tolérance à l'effort maximal significativement réduite par rapport aux pairs en bonne santé. Nous avons dénombré neuf programmes d'entraînement ayant servi exclusivement à des études portant sur des patients âgés de 20 ans ou moins qui avaient subi l'intervention de Fontan. La durée des programmes allait de six semaines à 12 mois. Huit programmes intégraient des activités aérobiques et un était axé uniquement sur l'entraînement musculaire inspiratoire. Les résultats pour au moins un indicateur de la tolérance à l'effort maximal ou sous-maximal se sont améliorés de façon significative dans chaque programme comportant une analyse statistique, sans qu'aucun événement indésirable soit signalé. Nous avons recensé deux autres programmes d'entraînement dont les participants étaient principalement (plus de 65 %), mais pas exclusivement, des patients ayant subi l'intervention de Fontan. Conclusions: Dans l'ensemble, les résultats indiquent que les programmes d'entraînement à l'effort peuvent améliorer efficacement et en toute sécurité au moins un indicateur de la tolérance à l'effort chez les enfants ayant subi l'intervention de Fontan.