Search

Network approaches to psychopathology have become increasingly common in mental health research, with many theoretical and methodological developments quickly gaining traction. This article illustrates contemporary practices in applying network analytical tools, bridging the gap between network concepts and their empirical applications. We explain how we can use graphs to construct networks representing complex associations among observable psychological variables. We then discuss key network models, including dynamic networks, time-varying networks, network models derived from panel data, network intervention analysis, latent networks, and moderated models. In addition, we discuss Bayesian networks and their role in causal inference with a focus on cross-sectional data. After presenting the different methods, we discuss how network models and psychopathology theories can meaningfully inform each other. We conclude with a discussion that summarizes the insights each technique can provide in mental health research., (© 2024 The Author(s). International Journal of Methods in Psychiatric Research published by John Wiley & Sons Ltd.)

Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose.

Network psychometrics uses graphical models to assess the network structure of psychological variables. An important task in their analysis is determining which variables are unrelated in the network, i.e., are independent given the rest of the network variables. This conditional independence structure is a gateway to understanding the causal structure underlying psychological processes. Thus, it is crucial to have an appropriate method for evaluating conditional independence and dependence hypotheses. Bayesian approaches to testing such hypotheses allow researchers to differentiate between absence of evidence and evidence of absence of connections (edges) between pairs of variables in a network. Three Bayesian approaches to assessing conditional independence have been proposed in the network psychometrics literature. We believe that their theoretical foundations are not widely known, and therefore we provide a conceptual review of the proposed methods and highlight their strengths and limitations through a simulation study. We also illustrate the methods using an empirical example with data on Dark Triad Personality. Finally, we provide recommendations on how to choose the optimal method and discuss the current gaps in the literature on this important topic.

Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose.

As the majority of the global population resides in cities, it is imperative to understand urban well-being. While cities offer concentrated social and economic opportunities, the question arises whether these benefits translate to equitable levels of satisfaction in these domains. Using a robust and objective measure of urbanicity on a sample of 156,000 U.K. residents aged 40 and up, we find that urban living is associated with lower scores across seven dimensions of well-being, social satisfaction, and economic satisfaction. In addition, these scores exhibit greater variability within urban areas, revealing increased inequality. Last, we identify optimal distances in the hinterlands of cities with the highest satisfaction and the least variation. Our findings raise concern for the psychological well-being of urban residents and show the importance of nonlinear methods in urban research.

A standard curriculum for pediatric colonoscopy training has neither been required nor universally implemented in North American fellowship programs. This qualitative study assessed the needs of colonoscopy training in pediatric gastroenterology to determine the standardized components of procedural teaching. Focus groups with pediatric gastroenterology attendings, fellows, procedural nurses, and interviews with advanced endoscopists, all practicing at a single institution, were conducted between March and June 2018. Data were analyzed using thematic analysis principles. Four themes emerged: (1) lack of standardization of colonoscopy performance, (2) lack of professional development of procedure teaching skills, (3) need for teaching behaviors that promote learner's performance, and (4) barriers to effective teaching and learning. A conceptual framework was created for developing a standardized "train-the-trainer" curriculum. Our needs assessment supports expansion of efforts to make this comprehensive training available to all pediatric gastroenterologists involved in procedure teaching., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Competing Interests: Declaration of Competing Interest None.

Objectives: While most hospital-based, healthcare professionals are expected to teach and supervise, few receive training in education. We designed, implemented, and evaluated an interprofessional, hospital-based teaching certificate program based on experiential learning and reflective practice for healthcare professionals with little or no formal training in education., Methods: Participants attended educational seminars; incorporated new concepts, skills, and behaviors in their teaching; and submitted written reflections. Participants also met with an education coach, received feedback from a trained observer, and observed a "master teacher." We used descriptive statistics to analyze a survey distributed to the 2017-2019 cohort. We also analyzed written reflections to determine whether participants described a new teaching skill, concept, or behavior, and how they applied these to their teaching., Results: Survey completion rate was 15/20 (75%). Participants described feeling connected to an educator community, establishing educational alliances with senior educators, and learning teaching strategies from other certificate members outside their own profession. Participants indicated they are more likely to pursue educational innovation, leadership, and scholarship. In the reflections, 88% described incorporating a new concept in their teaching., Conclusion: Participants in an interprofessional teaching certificate program engaged in a curriculum of professional development in education. Graduates of the program reported knowledge gain, behavior change, and establishment of educational alliances and a community of practice., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Objectives: Prior research suggests that errors occur frequently for patients with medical complexity during the hospital-to-home transition. Less is known about effective postdischarge communication strategies for this population. We aimed to assess rates of 30-day (1) postdischarge incidents and (2) readmissions and emergency department (ED) visits before and after implementing a hospital-to-home intervention., Methods: We conducted a prospective intervention study of children with medical complexity discharged at a children's hospital from April 2018 to March 2020. A multistakeholder team developed a bundled intervention incorporating the I-PASS handoff framework including a postdischarge telephone call, restructured discharge summary, and handoff communication to outpatient providers. The primary outcome measure was rate of postdischarge incidents collected via electronic medical record review and family surveys. Secondary outcomes were 30-day readmissions and ED visits., Results: There were 199 total incidents and the most common were medication related (60%), equipment issues (15%), and delays in scheduling/provision of services (11%). The I-PASS intervention was associated with a 36.4% decrease in the rate of incidents per discharge (1.51 versus 0.95, P = 0.003). There were fewer nonharmful errors and quality issues after intervention (1.27 versus 0.85 per discharge, P = 0.02). The 30-day ED visit rate was significantly lower after intervention (12.6% versus 3.4%, per 100 discharges, P = 0.05). Thirty-day readmissions were 15.8% versus 10.2% postintervention (P = 0.32)., Conclusions: A postdischarge communication intervention for patients with medical complexity was associated with fewer postdischarge incidents and reduced 30-day ED visits. Standardized postdischarge communication may play an important role in improving quality and safety in the transition from hospital-to-home for vulnerable populations., Competing Interests: A.J.S. holds equity in and has consulted with the I-PASS Patient Safety Institute. The I-PASS Patient Safety Institute is a company that seeks to train institutions in best handoff practices and aid in their implementation. The I-PASS Patient Safety Institute was in no way involved in this study. Moreover, to ensure objectivity, all data were analyzed via a statistical team who do not have any involvement with the I-PASS Patient Safety Institute. All analyses were conducted by this statistical team. A.J.S. has received monetary awards, honoraria, and travel reimbursement from multiple academic and professional organizations for teaching and consulting on physician performance and handoffs. The other authors disclose no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The Ising model is a graphical model that has played an essential role in network psychometrics. It has been used as a theoretical model to conceptualize psychological concepts and as a statistical model to analyze psychological data. Using graphical models such as the Ising model to analyze psychological data has been heavily critiqued since these data often come from cross-sectional applications. An often voiced concern is the inability of the Ising model to express heterogeneity in the population. The idiographic approach has been posed as an alternative and aims to infer individual network structures. While idiographic networks overcome population heterogeneity, it is unclear how they aggregate into established cross-sectional phenomena. This paper establishes a formal bridge between idiographic and cross-sectional network approaches of the Ising model. We ascertain unique topological structures that characterize individuals and aggregate into an Ising model cross-sectionally. This new formulation supports population heterogeneity while being consistent with cross-sectional phenomena. The proposed theory also establishes a new statistical framework for analyzing populations of idiographic networks for binary variables. The Ising model and the divide and color model are special cases of this new framework. We introduce a Gibbs sampling algorithm to estimate models from this new framework.

Allergic inflammation of the airways such as allergic asthma is a major health problem with growing incidence world-wide. One cardinal feature in severe type 2-dominated airway inflammation is the release of lipid mediators of the eicosanoid family that can either promote or dampen allergic inflammation. Macrophages are key producers of prostaglandins and leukotrienes which play diverse roles in allergic airway inflammation and thus require tight control. Using RNA- and ATAC-sequencing, liquid chromatography coupled to mass spectrometry (LC-MS/MS), enzyme immunoassays (EIA), gene expression analysis and in vivo models, we show that the aryl hydrocarbon receptor (AhR) contributes to this control via transcriptional regulation of lipid mediator synthesis enzymes in bone marrow-derived as well as in primary alveolar macrophages. In the absence or inhibition of AhR activity, multiple genes of both the prostaglandin and the leukotriene pathway were downregulated, resulting in lower synthesis of prostanoids, such as prostaglandin E2 (PGE 2 ), and cysteinyl leukotrienes, e.g., Leukotriene C4 (LTC 4 ). These AhR-dependent genes include PTGS1 encoding for the enzyme cyclooxygenase 1 (COX1) and ALOX5 encoding for the arachidonate 5-lipoxygenase (5-LO) both of which major upstream regulators of the prostanoid and leukotriene pathway, respectively. This regulation is independent of the activation stimulus and partially also detectable in unstimulated macrophages suggesting an important role of basal AhR activity for eicosanoid production in steady state macrophages. Lastly, we demonstrate that AhR deficiency in hematopoietic but not epithelial cells aggravates house dust mite induced allergic airway inflammation. These results suggest an essential role for AhR-dependent eicosanoid regulation in macrophages during homeostasis and inflammation., 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., (Copyright © 2023 Maier, Huth, Alessandrini, Schnautz, Arifovic, Riols, Haid, Koegler, Sameith, Schmidt-Weber, Esser-von-Bieren and Ohnmacht.)

Problem: Incorporating patient and family voices in the development of entrustable professional activities (EPAs) is not standard practice. Care of children with medical complexity (CMC) is an area of pediatrics that relies on family partnership, and families of CMC are ideal partners in EPA development given their expertise in their child's care and experience interacting with the health care system. The authors describe their model for partnering with families to develop EPAs and reflect on the unique contributions of family leaders to the process., Approach: After recruitment of family leaders from a national organization of families and friends of children with special health care needs, the authors used a multistage process for EPA development from June 2019 to February 2021. Family leaders were integrated throughout the process, including creating EPA descriptions, revising content across all EPAs, appraising EPAs through virtual focus groups with other key stakeholders, and finalizing and publishing EPAs. The authors used content analysis to identify recommendations for patient- and family-integrated EPA development., Outcomes: Family leaders and educators partnered in every phase of developing EPAs for the care of CMC, including as content experts, editors, focus group facilitators, and coauthors. Family leaders recommended substantive changes to all EPAs, including revising language, augmenting content, and modifying scope of practice. In addition, content analysis of family leaders' revisions yielded 10 recommendations to ensure that written EPA descriptions are patient- and family-centered., Next Steps: The described process of EPA development for the care of CMC models how families can be integrated into competency framework development and highlights their contributions. Family leader recommendations for embedding patient and family voices in EPA descriptions can serve as a guide for EPA development in other specialties., (Copyright © 2022 by the Association of American Medical Colleges.)

Purpose: Clinical fellows, those training to become subspecialists in a program certified by the Accreditation Council for Graduate Medical Education, supervise residents on inpatient subspecialty rotations. Unlike for supervising residents or for faculty, there is a paucity of literature describing fellows' supervision of residents. The aim of this study was to understand residents' and fellows' perception of successful supervision of residents by fellows on inpatient subspecialty rotations to inform the development of curricula to support fellows as supervisors., Method: Using grounded theory methodology, the authors held focus groups in May 2020 of pediatric residents and pediatric subspecialty fellows at Boston Children's Hospital, Boston, Massachusetts. Focus groups were conducted until thematic saturation was achieved. Deidentified transcripts were independently coded by 2 authors. The author team consolidated the codes into themes and developed an interpretive model for fellows' successful supervision of residents. Key results were confirmed via member checking., Results: The authors conducted 4 resident focus groups, composed of 16 pediatric residents, and 4 fellow focus groups, composed of 13 pediatric subspecialty fellows. Participants perceived that fellows who provided successful resident supervision advanced residents' professional growth and supported residents' development along 5 "bridges": (1) generalist to subspecialist, (2) trainee to autonomous practitioner, (3) individual to member of the interprofessional team, (4) emerging physician to patient-facing care provider, and (5) newcomer to engaged clinical learner. Fellows can further residents' growth in these areas by demonstrating approachability, empathy, appreciation, and kindness., Conclusions: As newcomers on inpatient subspecialty rotations, residents engage in legitimate peripheral participation. Fellows who are successful supervisors move residents toward full participation in their profession via the bridge model. The fellow-resident dynamic carries advantages of near-peer learning. Fellows can harness their role, subspecialty knowledge, and familiarity with the training environment to enhance resident supervision., (Copyright © 2022 by the Association of American Medical Colleges.)

Objective: To identify gaps and opportunities in complex care training for pediatric residents., Methods: Residents in an academic pediatric residency program were surveyed about: training experiences in complex care; self-entrustment in key clinical activities in complex care; educational strategies that would increase preparedness; and recommendations for curriculum development. We used descriptive statistics for quantitative data and content analysis for free-text responses., Results: Of the 160 residents surveyed, 110 (69%) participated. Most participants reported prior clinical exposure to children with medical complexity (CMC; 106, 96%) during both inpatient (82, 75%) and outpatient (88, 80%) clinical rotations. Mean self-entrustment was at or below "somewhat confident" for all clinical activities in complex care, for residents in all postgraduate years. Clinical activities with highest reported self-entrustment included evaluating aspiration into the airway, nutritional issues, care coordination, and evaluating pain. Lowest self-entrustment was reported for facilitating transition to adult care, managing medical technologies, and safety/emergency planning. In terms of educational strategies, participants recommended inpatient encounters with an expert preceptor teaching about evaluating aspiration, pain/irritability and dysmotility (>50%); discussions with patients/families for advocacy, difficult discussions, and transition to adult care (>40%); and hands-on practice for medical technology care (>40%)., Conclusions: Pediatric residents report limited self-entrustment in performing key clinical activities in complex care, including for residents at the end of their last postgraduate year. Future curriculum development should prioritize direct observation of clinical encounters with CMC by expert preceptors, partnership with patients and families of CMC, and hands-on simulation., (Copyright © 2022 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Testing the equality of two proportions is a common procedure in science, especially in medicine and public health. In these domains, it is crucial to be able to quantify evidence for the absence of a treatment effect. Bayesian hypothesis testing by means of the Bayes factor provides one avenue to do so, requiring the specification of prior distributions for parameters. The most popular analysis approach views the comparison of proportions from a contingency table perspective, assigning prior distributions directly to the two proportions. Another, less popular approach views the problem from a logistic regression perspective, assigning prior distributions to logit-transformed parameters. Reanalyzing 39 null results from the New England Journal of Medicine with both approaches, we find that they can lead to markedly different conclusions, especially when the observed proportions are at the extremes (ie, very low or very high). We explain these stark differences and provide recommendations for researchers interested in testing the equality of two proportions and users of Bayes factors more generally. The test that assigns prior distributions to logit-transformed parameters creates prior dependence between the two proportions and yields weaker evidence when the observations are at the extremes. When comparing two proportions, we argue that this test should become the new default., (© 2021 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.)

Background: Care of children with medical complexity (CMC) involves unique knowledge, skills, and attitudes. Previous work has identified curricular priorities in complex care for pediatricians yet there are no established competency frameworks to guide curriculum development. We aimed to develop and appraise Entrustable Professional Activities (EPAs) for the care of CMC with multistakeholder involvement., Methods: We recruited complex care practitioners to develop EPAs using a template for elaborating descriptive elements. A team of clinicians, educators, trainees, and family leaders refined EPAs and mapped content to the Accreditation Council for Graduate Medical Education Milestones. We conducted virtual focus groups to assess whether EPAs represented the essential skills of pediatricians caring for CMC. Focus group data were analyzed using content analysis., Results: Content experts developed 11 EPAs for the care of CMC describing knowledge, skills, and attitudes required for attaining competency. EPAs were mapped to 21 of the 21 (100%) reporting pediatric milestones. Focus group participants endorsed and refined EPA content. Categories of feedback included clarifying medical knowledge, expanding on interpersonal communication skills, emphasizing systems-based practice, and affirming family partnership., Conclusions: A systematic approach to developing EPAs for the care of CMC provides a guide for curriculum development and assessment in complex care., (Copyright © 2021 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

The Ising model is one of the most widely analyzed graphical models in network psychometrics. However, popular approaches to parameter estimation and structure selection for the Ising model cannot naturally express uncertainty about the estimated parameters or selected structures. To address this issue, this paper offers an objective Bayesian approach to parameter estimation and structure selection for the Ising model. Our methods build on a continuous spike-and-slab approach. We show that our methods consistently select the correct structure and provide a new objective method to set the spike-and-slab hyperparameters. To circumvent the exploration of the complete structure space, which is too large in practical situations, we propose a novel approach that first screens for promising edges and then only explore the space instantiated by these edges. We apply our proposed methods to estimate the network of depression and alcohol use disorder symptoms from symptom scores of over 26,000 subjects., (© 2022. The Author(s).)

Objectives: Cerebral palsy (CP) is the most common childhood motor disability, yet its link to single-gene disorders is under-characterized. To explore the genetic landscape of CP, we conducted whole exome sequencing (WES) in a cohort of patients with CP., Methods: We performed comprehensive phenotyping and WES on a prospective cohort of individuals with cryptogenic CP (who meet criteria for CP; have no risk factors), non-cryptogenic CP (who meet criteria for CP; have at least one risk factor), and CP masqueraders (who could be diagnosed with CP, but have regression/progressive symptoms). We characterized motor phenotypes, ascertained medical comorbidities, and classified brain MRIs. We analyzed WES data using an institutional pipeline., Results: We included 50 probands in this analysis (20 females, 30 males). Twenty-four had cryptogenic CP, 20 had non-cryptogenic CP, five had CP masquerader classification, and one had unknown classification. Hypotonic-ataxic subtype showed a difference in prevalence across the classification groups (p = 0.01). Twenty-six percent of participants (13/50) had a pathogenic/likely pathogenic variant in 13 unique genes (ECHS1, SATB2, ZMYM2, ADAT3, COL4A1, THOC2, SLC16A2, SPAST, POLR2A, GNAO1, PDHX, ACADM, ATL1), including one patient with two genetic disorders (ACADM, PDHX) and two patients with a SPAST-related disorder. The CP masquerader category had the highest diagnostic yield (n = 3/5, 60%), followed by the cryptogenic CP category (n = 7/24, 29%). Fifteen percent of patients with non-cryptogenic CP (n = 3/20) had a Mendelian disorder on WES., Interpretation: WES demonstrated a significant prevalence of Mendelian disorders in individuals clinically diagnosed with CP, including in individuals with known CP risk factors., (© 2022 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Macroautophagy/autophagy plays an important role in cellular copper clearance. The means by which the copper metabolism and autophagy pathways interact mechanistically is vastly unexplored. Dysfunctional ATP7B, a copper-transporting ATPase, is involved in the development of monogenic Wilson disease, a disorder characterized by disturbed copper transport. Using in silico prediction, we found that ATP7B contains a number of potential binding sites for LC3, a central protein in the autophagy pathway, the so-called LC3 interaction regions (LIRs). The conserved LIR3, located at the C-terminal end of ATP7B, was found to directly interact with LC3B in vitro. Replacing the two conserved hydrophobic residues W1452 and L1455 of LIR3 significantly reduced interaction. Furthermore, autophagy was induced in normal human hepatocellular carcinoma cells (HepG2) leading to enhanced colocalization of ATP7B and LC3B on the autophagosome membranes. By contrast, HepG2 cells deficient of ATP7B (HepG2 ATP7B -/- ) showed autophagy deficiency at elevated copper condition. This phenotype was complemented by heterologous ATP7B expression. These findings suggest a cooperative role of ATP7B and LC3B in autophagy-mediated copper clearance.

Ponazuril, a novel coccidiocidal triazinetrione, has shown promise in addressing apicomplexan diseases in mammals and birds. This study describes the pharmacokinetics of ponazuril in healthy adult Indian peafowl ( Pavo cristatus ) following a single oral dose administered at two different dosages. Peafowl (four males and four females) were administered compounded ponazuril at 20 or 40 mg/kg orally in a double crossover design, with a 2-wk washout period. Blood was collected from each bird at 2, 4, 8, 24, 48, 72, 96, and 120 h after administration for plasma concentration of ponazuril using high-pressure liquid chromatography. Fecals were evaluated for coccidial shedding for 3 consecutive d prior to the ponazuril trial, 1 wk after the first dose of ponazuril, and 1 wk after the second dose of the trial. After the first trial, one peafowl administered 20 mg/kg ponazuril was shedding coccidia, but no coccidia were detected by the end of the second trial. Ponazuril reached peak concentrations ( T max ) at 21.38 h + 5.25 and 22.04 h + 7.39, and peak concentration ( C max ) were 11.82 µg/ml + 3.01 and 18.42 µg/ml + 4.13, for 20 and 40 mg/kg doses, respectively. Ponazuril was detected at 120 h with a concentration of 9.48 µg/ml + 2.59 and 12.25 µg/ml + 2.89 and a half-life of 219.4 + 58.7 h and 186.7 + 58.7 h, for and 40 mg/kg doses, respectively. Ponazuril in peafowl was well absorbed orally, plasma concentrations increased with dose, and elimination was slower than current dosages for birds would suggest. No obvious adverse effects were observed at either dosage.

Time to reporting antimicrobial susceptibility testing (AST) results to physicians plays an essential role in antibiotic stewardship programs. Expert software has been developed for facilitating the microbiologists' AST review process. The reliability of the VITEK®2 Advanced Expert™ software to effectively alert the microbiologist in detection of atypical and inconsistent AST results was assessed at the Labor Berlin-Charité Vivantes services. The results demonstrated a confidence rate of 99.3% in reporting fully consistent AST results to physicians.

Background: Miscommunications during care transfers are a leading cause of medical errors. Recent consensus-based recommendations to standardise information transfer from outpatient clinics to the emergency department (ED) have not been formally evaluated. We sought to determine whether a receiver-driven structured handoff intervention is associated with 1) increased inclusion of standardised elements; 2) reduced miscommunications and 3) increased perceived quality, safety and efficiency., Methods: We conducted a prospective intervention study in a paediatric ED and affiliated clinics in 2016-2018. We developed a bundled handoff intervention included a standard template, receiver training, awareness campaign and iterative feedback. We assessed a random sample of audio-recorded handoffs and associated medical records to measure rates of inclusion of standardised elements and rate of miscommunications. We surveyed key stakeholders pre-intervention and post-intervention to assess perceptions of quality, safety and efficiency of the handoff process., Results: Across 162 handoffs, implementation of a receiver-driven intervention was associated with significantly increased inclusion of important elements, including illness severity (46% vs 77%), tasks completed (64% vs 83%), expectations (61% vs 76%), pending tests (0% vs 64%), contingency plans (0% vs 54%), detailed callback request (7% vs 81%) and synthesis (2% vs 73%). Miscommunications decreased from 48% to 26%, a relative reduction of 23% (95% CI -39% to -7%). Perceptions of quality (35% vs 59%), safety (43% vs 73%) and efficiency (17% vs 72%) improved significantly post-intervention., Conclusions: Implementation of a receiver-driven intervention to standardise clinic-to-ED handoffs was associated with improved communication quality. These findings suggest that expanded implementation of similar programmes may significantly improve the care of patients transferred to the paediatric ED., Competing Interests: Competing interests: NS, AJS and DCW have consulted with and hold equity in the I-PASS Patient Safety Institute, which seeks to train institutions in best handoff practices and aid in their implementation. NS, AJS and DCW also reported receiving honoraria and travel reimbursement from multiple academic and professional organisations for delivering lectures on handoffs and patient safety., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

The synthesis of a sulfate-modified dendritic peptide amphiphile and its self-assembly into one-dimensional rod-like architectures in aqueous medium is reported. The influence of the ionic strength on the supramolecular polymerization was probed via circular dichroism spectroscopy and cryogenic transmission electron microscopy. Physiological salt concentrations efficiently screen the charges of the dendritic building block equipped with eight sulfate groups and trigger the formation of rigid supramolecular polymers. Since multivalent sulfated supramolecular structures mimic naturally occurring L-selectin ligands, the corresponding affinity was evaluated using a competitive SPR binding assay and benchmarked to an ethylene glycol-decorated supramolecular polymer., (Copyright © 2021, Straßburger et al.; licensee Beilstein-Institut.)

Interprofessional trust is essential for effective team-based care. Medical students are transient members of clinical teams during clerkship rotations and there may be limited focus on developing competency in interprofessional collaboration. Within a pediatric clerkship rotation, we developed a novel simulation activity involving an interprofessional conflict, aiming to foster trusting interprofessional relationships. Active participants included a nurse educator and a medical student participant, with additional students using a checklist to actively observe. The debrief focused on teaching points related to interprofessional competencies and conflict resolution. Students completed a written evaluation immediately following the simulation. Descriptive statistics were used to analyze Likert-type scale questions. Conventional content analysis was used to analyze open-ended responses. Two hundred and fourteen students participated in the simulation between June 2018-June 2019. Most students indicated that the simulation was effective (86%) and improved their confidence to constructively manage disagreements about patient care (88%). Students described anticipated changes in practice including developing their role on the interprofessional team as a medical student, developing a shared mental model, and establishing a shared goal. Our findings suggest that simulation-based learning may present an opportunity for developing interprofessional trust in academic health centers.

Niemann-Pick disease type C1 (NPC1) is a rare inherited lipid storage disorder caused by mutations in the NPC1 gene. Mutations lead to impaired lipid trafficking and subsequently to accumulation of cholesterol and sphingolipids. NPC1-patients present variable multisystemic symptoms, including neurological deficits. Here, we describe the generation of human iPSC lines obtained from fibroblasts of a male individual, carrying the homozygous mutation p.I1061T, and an unrelated and healthy male individual. A non-integrating Sendai virus system, containing KLF4, OCT3/4, SOX2 and C-MYC, was used for reprogramming. These cell lines provide a valuable resource for studying the pathophysiology of multisystemic NPC1-disease., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Due to advances in medical care and innovations in health technology, many children with life-limiting conditions are now living longer. These children are often referred to as 'children with medical complexity (CMC)', and they are characterized by chronic conditions, increased health care utilization, and technology dependence. Their complexity of care and inherent fragility lead to higher risk for medication errors, both in-community and in-hospital. High rates of care fragmentation, miscommunication, and polypharmacy in CMC increase opportunities for error, particularly as children transition between health care settings and practitioners. Data on the factors contributing to higher risk of medication errors in this population and how they can be effectively addressed are lacking. This practice point provides clinical guidance for health care professionals to ensure medication safety when caring for CMC, with focus on practical strategies for outpatient and inpatient care., (© Canadian Paediatric Society 2020. Published by Oxford University Press on behalf of the Canadian Paediatric Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Grâce aux progrès de la médecine et aux innovations en technologies de la santé, de nombreux enfants atteints d'affections au pronostic réservé vivent désormais plus longtemps. Ces enfants sont souvent qualifiés d'« enfants ayant des problèmes médicaux complexes », parce qu'ils ont des affections chroniques, utilisent davantage les soins de santé et sont dépendants de la technologie. La complexité de leurs soins et leur fragilité intrinsèque entraînent des risques plus élevés d'erreurs de médication, autant dans un contexte ambulatoire qu'hospitalier. Le taux élevé de fragmentation des soins, de mauvaise communication et de polypharmacie chez les enfants ayant des problèmes médicaux complexes accroissent les possibilités d'erreurs, particulièrement au moment de changer de milieu de soins et de praticiens. Il n'existe pas de données sur les facteurs qui contribuent à un risque plus élevé d'erreurs de médication dans cette population et sur les meilleures mesures pour les éviter. Le présent point de pratique fournit des directives cliniques aux professionnels de la santé afin de s'assurer d'une utilisation sécuritaire des médicaments auprès des enfants ayant des problèmes médicaux complexes et s'attarde sur des stratégies pratiques applicables à la fois en soins ambulatoires et hospitaliers., (© Société canadienne de pédiatrie 2020. Publié par Oxford University Press pour le compte de la Société canadienne de pédiatrie. Tous droits réservés. Pour obtenir une autorisation, écrivez à journals.permissions@oup.com.)

Purpose: To explore resident and attending physician perceptions of resident behaviors and skills that demonstrate trustworthiness and promote entrustment by supervisors., Method: Using grounded theory methodology, the authors conducted 3 focus groups with pediatric residents from the Boston Combined Residency Program and 3 focus groups with attending physicians who were either general pediatric hospitalists or other pediatric subspecialists at Boston Children's Hospital and Boston Medical Center in Boston, Massachusetts, from May to December 2018. Data were collected and analyzed iteratively until theoretical saturation was achieved. Three independent reviewers coded each transcript. Codes were grouped into dominant themes to develop a conceptual model., Results: Twelve residents and 18 attending physicians participated in the focus groups. Participants described actions that they felt actively demonstrated residents' trustworthiness within previously described domains of trustworthiness. Four modifiers emerged that affect a resident's progression from trustworthiness to entrustment: (1) self-management, (2) relationships, (3) self-advocacy, and (4) patient-centeredness. Findings were synthesized into a conceptual model depicting how trainees can promote their own entrustment by supervisors., Conclusions: Trainees must actively demonstrate their trustworthiness to be entrusted. This study proposes that trainees can further gain entrustment through self-management, relationships, self-advocacy, and patient-centeredness. When they understand the actions and behaviors that promote entrustment, trainees may be better able to foster autonomy and progress toward more independent clinical practice. These findings add to existing evidence regarding entrustment and provide a novel, actionable framework for trainees to increase their own entrustment.

Oxidative stress (OS) represents a state of an imbalanced amount of reactive oxygen species (ROS) and/or a hampered efficacy of the antioxidative defense system. Cells of the central nervous system are particularly sensitive to OS, as they have a massive need of oxygen to maintain proper function. Consequently, OS represents a common pathophysiological hallmark of neurodegenerative diseases and is discussed to contribute to the neurodegeneration observed amongst others in Alzheimer's disease and Parkinson's disease. In this context, accumulating evidence suggests that OS is involved in the pathophysiology of Niemann-Pick type C1 disease (NPC1). NPC1, a rare hereditary neurodegenerative disease, belongs to the family of lysosomal storage disorders. A major hallmark of the disease is the accumulation of cholesterol and other glycosphingolipids in lysosomes. Several studies describe OS both in murine in vivo and in vitro NPC1 models. However, studies based on human cells are limited to NPC1 patient-derived fibroblasts. Thus, we analyzed OS in a human neuronal model based on NPC1 patient-specific induced pluripotent stem cells (iPSCs). Higher ROS levels, as determined by DCF (dichlorodihydrofluorescein) fluorescence, indicated oxidative stress in all NPC1-deficient cell lines. This finding was further supported by reduced superoxide dismutase (SOD) activity. The analysis of mRNA and protein levels of SOD1 and SOD2 did not reveal any difference between control cells and NPC1-deficient cells. Interestingly, we observed a striking decrease in catalase mRNA and protein levels in all NPC1-deficient cell lines. As catalase is a key enzyme of the cellular antioxidative defense system, we concluded that the lack of catalase contributes to the elevated ROS levels observed in NPC1-deficient cells. Thus, a restitution of a physiological catalase level may pose an intervention strategy to rescue NPC1-deficient cells from the repercussions of oxidative stress contributing to the neurodegeneration observed in NPC1.

Background: There are limited training opportunities for pediatricians in caring for children with medical complexity (CMC) in the home and community. Prior studies have described a lack of comfort caring for CMC among pediatric residents., Objective: 1) To evaluate the impact of participation in a virtual home visit curriculum on pediatric residents' confidence, knowledge, and application of knowledge in complex care; 2) to explore changes in perspectives relating to the care of CMC after participation in the curriculum., Methods: This was a prospective pre-post intervention study in 2019 with first-year pediatric residents, using quantitative and qualitative methods. The intervention, co-created with a family partner, was an online video-based curriculum followed by an in-person seminar. Pre- and postassessments were compared using paired t tests. Follow-up interviews and focus groups were performed 5 to 8 weeks after training. Transcripts were analyzed using inductive thematic analysis., Results: Twenty-four residents (100%) participated. Residents reported increased confidence in all aspects of complex care presented in the curriculum, with significant increase in knowledge and application of knowledge (all P < .001). Twelve residents (50%) participated in a follow-up interview or focus group. Four themes were identified: 1) recognizing prior attitudes toward complexity, 2) new mental framework for complex care at home, 3) drivers of behavior change, and 4) commitment to change practice., Conclusions: Participation in this curriculum was associated with increased confidence, knowledge, and application of knowledge in complex care outside of the hospital. Qualitative findings align with transformative learning theory, lending insight into effective approaches to complex care training., (Copyright © 2020 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Background: Previous studies of pediatric residents have identified educational gaps in caring for children with medical complexity. Training opportunities in complex care vary across residency programs. Defining core curricular topics in complex care is a priority in medical education., Objective: To identify core topics to include in a standard complex care curriculum for pediatric residents., Methods: An initial topic list was generated through literature review and proceedings of national meetings. Expert panelists were identified based on experience in complex care and residency education. A modified Delphi method was used to determine group consensus by asking participants to rate the importance of complex care curricular topics for pediatric residents. Consensus was defined as >70% of experts identifying a topic as essential. There was a predetermined maximum of 3 iterative, electronic survey rounds, with feedback provided to participants between each round., Results: Sixteen experts participated. Response rate was 100% for all rounds. Experts were from the United States (44%) and Canada (56%); most were affiliated with an academic medical center (96%) involved in both inpatient and outpatient care (69%). Eleven topics were identified as essential across 3 rounds: feeding difficulties, pain/irritability, transition, feeding tube management, difficult discussions, team management/care coordination, dysmotility, aspiration, safety/emergency planning, neuromuscular/skeletal issues, and advocacy. Essential topics were organized according to the International Classification of Functioning, Disability and Health., Conclusions: Eleven curricular priorities in complex care were identified across multiple domains of the International Classification of Functioning, Disability and Health framework, serving as a guide for standardized curriculum development for future pediatricians., (Copyright © 2020 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Objective: Children with medical complexity (CMC) are a growing population, yet training in complex care varies across pediatric residency programs. The purpose of this study was 1) to evaluate the effectiveness of a curriculum for pediatric residents in improving performance in a simulated clinical scenario, and 2) to explore residents' perceived self-efficacy in caring for CMC., Methods: A randomized controlled trial was conducted supplemented by qualitative inquiry. Pediatric residents from 2 residency programs were randomly assigned to participate in interactive modules on: 1) clinical assessment, care planning, and technological dependency or 2) noncomplex care topics. The primary outcome was mean score on an Observed Structured Clinical Examination (OSCE) of tracheostomy care. Semistructured interviews were conducted postintervention and analyzed using qualitative content analysis., Results: Ninety-four eligible residents were randomized. Residents who attended all modules and the OSCE and consented to participate (intervention [n = 20] and control [n=24]) were included in the final analysis. At baseline, few (9%) reported being comfortable caring for CMC. There was no significant difference in mean OSCE score between intervention and control groups (39.0 ± 1.1 vs 38.0 ± 1.0, P = .48). Qualitative analysis revealed 3 emerging themes related to resident self-efficacy: building a system of care, navigating uncertainty, and professional identity formation., Conclusions: A standardized complex care curriculum delivered in a classroom setting did not lead to improved performance in an OSCE station despite increased resident-reported self-efficacy in approaching care for CMC. These findings highlight the need for multidimensional educational interventions and assessments in complex care., (Copyright © 2019 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: The majority of patient care occurs in the ambulatory setting, and pediatric patients are at high risk of medical error and harm. Prior studies have described various safety threats in ambulatory pediatrics, and little is known about effective strategies to minimize error. The purpose of this review is to identify best practices for optimizing safety in ambulatory pediatrics., Recent Findings: The majority of the patient safety literature in ambulatory pediatrics describes frequencies and types of medical errors. Study of effective interventions to reduce error, and particularly to reduce harm, have been limited. There is evidence that medical complexity and social context are important modifiers of risk. Telemedicine has emerged as a care delivery model with potential to ameliorate and exacerbate safety threats. Though there is variation across studies, developing a safety culture, partnerships with patients and families, and use of structured communication are strategies that support patient safety., Summary: There is no standardized taxonomy for errors in ambulatory pediatrics, but errors related to medications, vaccines, diagnosis, and care coordination and care transitions are commonly described. Evidence-based approaches to optimize safety include standardized prescribing and medication reconciliation practices, appropriate use of decision support tools in the electronic health record, and communication strategies like teach-back. Further high-quality intervention studies in pediatric ambulatory care that assess impact on patient harm and clinical outcomes should be prioritized., (© Springer Nature Switzerland AG 2020.)

Background: Changes to assessment efforts following the shift to milestones-based assessment in the ACGME Next Accreditation System have not been fully characterized., Objective: This study describes themes in initial milestones-based assessment practices with the goal of informing continued implementation and optimization of milestones-based assessment., Methods: Semistructured interviews were conducted with 15 residency program leaders in 6 specialties at 8 academic medical centers between August and December 2016. We explored what was retained, what was added, and what was changed from pre-milestones assessment efforts. We also examined the perceived impact of the shift to milestones-based assessment on the programs. Thematic analysis began after the first 5 interviews and ended once thematic sufficiency was reached. Two additional authors reviewed the codes, offered critical input, and informed the formation and naming of the final themes., Results: Three themes were identified: (1) program leaders faced challenges to effective implementation; (2) program leaders focused on adaptability and making milestones work in what felt like a less than ideal situation for them; and (3) despite challenges, program leaders see value and utility in their efforts to move to milestones-based assessment. We describe a number of strategies that worked for programs during the transition, with perceived benefits acknowledged., Conclusions: While adaptation to milestones has occurred and benefits are noted, negative impacts and challenges (eg, perceived lack of implementation guidance and faculty development resources) persist. There are important lessons learned (eg, utilizing implementation experiences formatively to improve curricula and assessment) in the transition to milestones-based assessment., Competing Interests: Conflict of interest: The authors declare they have no competing interests.

Background/objective: Undergraduate medical education still relies on lectures as the core teaching activity. However, e-learning and new media have begun to augment learning and information gathering over the last few years. The aim of this study was to investigate the effect of 2 teaching formats in surgical education, a classic lecture and a video podcast (vodcast), on knowledge gain, in particular with respect to the participants' characteristics and preferences., Design: A prospective study was conducted over 2 consecutive semesters. A traditional lecture on goitre was given to the first of the 2 semesters and replaced by a matching vodcast made available to the second. An untaught subject (cholelithiasis) served as control. Knowledge gain was calculated as the difference in point scores between entry and mid-module examinations. Furthermore, participants completed a postintervention survey, in which they specifically rated their digital affinity and learning preferences. A cluster analysis was conducted pooling both semesters to evaluate differences between individuals affecting their performance., Results: Both teaching formats resulted in a significant knowledge gain. Two clusters could be identified across both semesters: Cluster 2 (Digital natives) proved to be significantly different from Cluster 1 (Traditional) with respect to the 4 variables: "technically interested," the "use of smartphones," "activity in social networks," and "reading in digital formats." The knowledge gain differences between formats for students in the "Traditional" cluster were statistically insignificant. However, students in the cluster "Digital natives" performed significantly worse when exposed to the lecture format., Conclusions: Cluster analysis revealed that the students with an obvious affinity to information communication technology were found to be at a significant disadvantage in the lecture. In future, we recommend offering some form of pretest to determine an individual's profile and empower students to plan their learning activities accordingly., (Copyright © 2018 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Direct observation of clinical skills is central to assessment in a competency-based medical education model, yet little is known about how direct observation is experienced by trainees and observers. The objective of the study is to explore how direct observation was experienced by residents and faculty in the context of the I-PASS Handoff Study. In this multi-center qualitative study, we conducted focus groups and semi-structured interviews of residents and faculty members at eight tertiary pediatric centers in North America that implemented the I-PASS Handoff Bundle. We employed qualitative thematic analysis to interpret the data. Barriers to and strategies for direct observation were described relating to the observer, trainee, and clinical environment. Residents and faculty described a mutual awareness that residents change their performance of handoffs when observed, in contrast to their usual behavior in a clinical setting. Changes in handoff performance may depend on the nature of the observer or 'audience'. Direct observation also highlighted the importance of handoffs to participants, recognized as a clinical activity that warrants feedback and assessment. Dramaturgical theory can be used to understand our finding of 'front-stage' (observed) versus 'backstage' (unobserved) handoffs as distinct performances, tailored to an "audience". Educators must be cognizant of changes in performance of routine clinical activities when using direct observation to assess clinical competence.

Background: Miscommunication during patient transfers is a leading cause of medical errors. Inpatient standardization of handoff communication has been associated with reduced medical errors, but less is known about best practices for handoffs from referring providers to the emergency department (ED). The study aims were to identify (1) stakeholder perceptions of current handoff processes and (2) key handoff elements and strategies to optimize patient care on transfer., Methods: A mixed-methods needs assessment study was conducted at a tertiary care children's hospital with a communication center that receives verbal handoff via telephone from referring providers and provides written summary to the ED. ED, primary care providers, and communication center staff were surveyed to understand perceptions of handoff processes and ideal handoff elements. Focus groups were conducted to refine concepts. Descriptive statistics, chi-square analysis, and qualitative content analysis were used to analyze responses., Results: The survey response rate was 129/152 providers (85%). Forty-two percent of respondents described the quality of the handoff process as "very good" or "excellent"; 43% reported miscommunication occurring "sometimes" or "frequently." Within the I-PASS framework-Illness severity, Patient summary, Action list, Situation awareness and contingency planning, and Synthesis by receiver-respondents identified 10 key elements to obtain through a receiver-driven process to optimize care on transfer. Free-text responses revealed a perceived need to standardize communication., Conclusion: A minority of providers perceived handoff quality between outpatient practices and the ED as "very good" or "excellent"; almost half perceived regular miscommunication. A receiver-driven process is a novel approach that may help ensure standardized communication of key handoff elements in this context., (Copyright © 2018 The Joint Commission. Published by Elsevier Inc. All rights reserved.)

Introduction: General pediatricians have a major role in the care of children with medical complexity (CMC) in hospital and community settings. CMC are often affected by chronic multisystem diseases and functional limitations and may use a wheelchair or other aids for mobility. Dedicated training opportunities to perform comprehensive clinical assessments for this specialized population are lacking., Methods: We developed a module focused on special considerations for CMC history taking and physical examination that was piloted in a pediatric residency program. The 60-minute session included a video of a clinical assessment of a child in a wheelchair. The module offered suggestions for incorporating patients or standardized patients as optional activities. Target learners answered formative pre- and posttest questions to check understanding and completed a 1-minute paper to convey lessons learned. Qualitative content analysis identified themes in written responses., Results: Fifteen pediatrics residents in a single program participated in the module. Most had not received any formal training in complex care. Themes in learner knowledge of steps in a clinical encounter included defining family goals and providing anticipatory guidance. Themes from responses about anticipated changes in clinical practice included systematic and comprehensive approach to history taking, thorough examination, and importance of safe transfers., Discussion: Developed as part of a national initiative in complex care curriculum development, this module can be adapted for interprofessional learners who provide care for CMC, with the goal of enabling future members of health care teams to provide high-quality clinical assessments for CMC., Competing Interests: None to report.

Fluorescent nanomaterials are expected to revolutionize medical diagnostic, imaging, and therapeutic tools due to their superior optical and structural properties. Their inefficient water solubility, cell permeability, biodistribution, and high toxicity, however, limit the full potential of their application. To overcome these obstacles, a water-soluble, fluorescent, cytocompatible polymer-single-walled carbon nanotube (SWNT) complex is introduced for bioimaging applications. The supramolecular complex consists of an alkylated polymer conjugated with neutral hydroxylated or charged sulfated dendronized perylene bisimides (PBIs) and SWNTs as a general immobilization platform. The polymer backbone solubilizes the SWNTs, decorates them with fluorescent PBIs, and strongly improves their cytocompatibility by wrapping around the SWNT scaffold. In photophysical measurements and biological in vitro studies, sulfated complexes exhibit superior optical properties, cellular uptake, and intracellular staining over their hydroxylated analogs. A toxicity assay confirms the highly improved cytocompatibility of the polymer-wrapped SWNTs toward surfactant-solubilized SWNTs. In microscopy studies the complexes allow for the direct imaging of the SWNTs' cellular uptake via the PBI and SWNT emission using the 1st and 2nd optical window for bioimaging. These findings render the polymer-SWNT complexes with nanometer size, dual fluorescence, multiple charges, and high cytocompatibility as valuable systems for a broad range of fluorescence bioimaging studies., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Introduction: Children with medical complexity (CMC) are characterized by chronic conditions, functional limitations, technology dependence, and high health care utilization. There are limited formal training opportunities in the provision of complex care for pediatric residents., Methods: We developed a module to enable target learners to understand unique needs of CMC and the general pediatrician's role in creating a medical home. The module was piloted in a single pediatric residency program. The 60-minute session incorporated small-group activities and didactic instruction. Learners were given formative pre- and posttest questions to check understanding and completed a 1-minute paper to summarize anticipated changes in practice. Qualitative content analysis was used to identify themes in written responses., Results: Fifteen pediatrics residents participated in the module at a single children's hospital. Most residents had not had a complex care clinical rotation. Themes in learner knowledge of CMC included recognizing functional limitations and recurrent health care utilization. Themes from anticipated changes in practice included having less fear/anxiety when approaching care for CMC and asking about diverse areas of need, including nonmedical., Discussion: This core module was developed as part of a national systematic approach to complex care curriculum development. It has the potential to be adapted to frame a broader complex care curriculum and to be implemented with other learners in the health professions who care for this vulnerable patient population. The pilot study informed implementation in multiple residency programs, with the goal of enabling future pediatricians to provide high-quality care within a medical home for CMC., Competing Interests: None to report.