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Austin J Allen,1,* Alexander B White,1,* Daniel R Bacon,2 Gary L Beck Dallaghan,3 Sheryl G Jordan4 1University of North Carolina School of Medicine, Chapel Hill, NC, USA; 2Department of Surgery, The Ohio State University College of Medicine, Columbus, OH, USA; 3Department of Medical Education, University of Texas at Tyler School of Medicine, Tyler, TX, USA; 4Department of Radiology, University of North Carolina School of Medicine, Chapel Hill, NC, USA*These authors contributed equally to this workCorrespondence: Sheryl G Jordan, University of North Carolina School of Medicine, 321 South Columbia Street, Chapel Hill, NC, 27514, USA, Tel +1 964 974 8123, Fax +1 919-966-9930, Email sheryl_jordan@med.unc.eduBackground: Ultrasound integration in undergraduate medical education (UME) has been a focused endeavor in recent years. According to the American Institute of Ultrasound in Medicine, more than a third of all US medical schools have adopted a focused ultrasound training program for medical students. Medical student perspectives on best practices in ultrasound education are lacking in the literature.Curricula Experiences: Two students’ reflections are presented regarding two different didactic approaches, flipped classroom and self-study learning models, to teaching ultrasound in the pre-clinical medical education curriculum. Students present reflections on these didactic approaches to facilitate further improvement in ultrasound education curricula.Discussion: The self-directed learning model enabled students to learn foundational ultrasound exam techniques efficiently in a low-stress environment and subsequently optimized the efficiency of later faculty-led learning events. However, we noted that in both the flipped classroom and self-study learning models of education, the training on basic physical properties of ultrasound, tissue characteristics, and probe manipulation was limited.Conclusion: A self-study learning model ultrasound curricula improves perceived learning efficiency and student confidence, especially when followed by faculty-guided didactics and scanning opportunities. We suggest a framework for ultrasound education curricula that includes components of both formats of ultrasound education alongside faculty-led sessions as an ideal model of ultrasound education. Further, we propose the added benefit of inanimate object scanning to optimize students’ knowledge of waveform physics (image acquisition and physical properties of materials) early in the ultrasound education process.Keywords: ultrasound, ultrasonography, ultrasonography education, education, medical, undergraduate

Daniel R Bacon,1 Keri Cowles,1 Diwash Thapa,1 Alexander White,1 Austin J Allen,1 John Doughton,2 Gary Beck Dallaghan,3 Sheryl G Jordan4 1University of North Carolina School of Medicine, Chapel Hill, NC, USA; 2Department of Family Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA; 3Office of Medical Education, University of North Carolina School of Medicine, Chapel Hill, NC, USA; 4Department of Radiology, University of North Carolina School of Medicine, Chapel Hill, NC, USACorrespondence: Sheryl G JordanUniversity of North Carolina School of Medicine, 321 South Columbia Street, Chapel Hill, NC, 27514, USAEmail sheryl_jordan@med.unc.eduIntroduction: Point of care ultrasound (POCUS) is increasingly prevalent and standardized in undergraduate medical education (UME); however, roughly 25% of United States medical schools lack an ultrasound curriculum. One of the commonly cited barriers to ultrasound training in UME is faculty time resources. Here, we describe an ultrasound scholarly concentration program (SCP) designed to provide medical students with ultrasound opportunities in clinical and scholarly domains, while reducing the need for extensive faculty resources.Methods: SCPs at the University of North Carolina School of Medicine have 3 requirements: an elective course, a longitudinal portfolio, and a final scholarly project. Thus, the ultrasound SCP was designed to comprise an introductory clinical elective to ultrasound, development of a longitudinal scan portfolio, and a final scholarly project in ultrasound related research or educational innovation. A review of the literature and search of the top 50 US medical schools by US News & World Report was performed to assess the novelty of the ultrasound SCP.Results: To the best of our knowledge, the ultrasound SCP is the first scholarly concentration, track or pathway offered to medical students in the United States. It is the first description of a student designed and student led curriculum focused on providing meaningful ultrasound opportunities to students without necessitating unavailable faculty resources and educational infrastructure.Conclusion: A novel ultrasound SCP is described which has clinical aims to expose students to clinical ultrasound as well as scholarly aims to facilitate ultrasound related research and educational innovation. It is designed to enable students to make ultrasound a defining characteristic of their medical school experience. The SCP relies on motivated student involvement and near-peer teaching in a way that is self-sustaining and self-improving.Keywords: ultrasound, ultrasound curriculum, undergraduate medical education, scholarly concentration

Objective To determine whether patients with obstructive sleep apnea (OSA) are at increased risk of occupational injury (OI) Methods Working patients (aged 18 to 65 who reported more than 10 h of work per week) who were referred to the University of British Columbia Sleep Laboratory for suspected OSA for polysomnogram (PSG) were recruited from 2003 to 2011. Patients completed an extensive survey the night of their PSG. Validated OI was obtained by linking patient data to Workers Compensation Board Claims Data. Results 1109 workers were studied; mean age was 47.1 years, median AHI was 15.0/h, median BMI was 30 kg/m.sup.2, 70.2% were male and 29% of patients worked in physical or manual related occupations. 78 patients (7.03%) suffered 140 OI in the 5 years after PSG. In a multivariate logistic regression model, OSA severity [defined as a log(AHI + 1)] was a significant predictor of OI (p = 0.04) after controlling for age, sex, BMI, and physical or manual related occupations. Patients with moderate and severe OSA had approximately two times the odds of an OI compared to patients without OSA (OR 1.99, 95% CI 0.96-4.44 and 2.00, 95% CI 0.96-4.49 for moderate and severe OSA groups, respectively). Conclusions In this prospective study, OSA severity was independently associated with an increased risk of OI., Author(s): AJ. Hirsch Allen [sup.1] , Bernardo Peres [sup.1] , Najib T. Ayas [sup.1] [sup.2] [sup.3] [sup.4] Author Affiliations: (1) grid.17091.3e, 0000 0001 2288 9830, Department of Medicine, University of [...]

OSA (obstructive sleep apnoea), the most common respiratory disorder of sleep, is caused by the loss of upper airway dilating muscle activity during sleep superimposed on a narrow upper airway. This results in recurrent nocturnal asphyxia. Termination of these events usually requires arousal from sleep and results in sleep fragmentation and hypoxaemia, which leads to poor quality sleep, excessive daytime sleepiness, reduced quality of life and numerous other serious health consequences. Furthermore, patients with untreated sleep apnoea are at an increased risk of hypertension, stroke, heart failure and atrial fibrillation. Although there are many predisposing risk factors for OSA, including male gender, endocrine disorders, use of muscle relaxants, smoking, fluid retention and increased age, the strongest risk factor is obesity. The aim of the present review is to focus on three cutting-edge topics with respect to OSA. The section on animal models covers various strategies used to simulate the physiology or the effects of OSA in animals, and how these have helped to understand some of the underlying mechanisms of OSA. The section on diabetes discusses current evidence in both humans and animal models demonstrating that intermittent hypoxia and sleep fragmentation has a negative impact on glucose tolerance. Finally, the section on cardiovascular biomarkers reviews the evidence supporting the use of these biomarkers to both measure some of the negative consequences of OSA, as well as the potential benefits of OSA therapies.

Objective: This study describes and assesses potential hepatobiliary events related to atomoxetine therapy, as reported in clinical trials and as spontaneous adverse event reports post-launch in 2002.Methods: Case reports that contained potential hepatobiliary events were identified by a computerized search of the Eli Lilly and Company atomoxetine spontaneous adverse events and clinical trials databases. All cases were reviewed by at least two company physicians, one with expertise in hepatology, to determine the relevance of the information in respect of potential liver toxicity.Results: Of 7961 paediatric and adult patients treated with atomoxetine in clinical trials, 41 were identified as having hepatobiliary events requiring additional analysis. Most of these events were mild increases in ALT and AST levels. None of these cases met Hy's rule criteria or progressed to liver failure. During the 4 years after market launch, 351 spontaneous reports of adverse events were related to the liver, of which 69 had other explanations unrelated to atomoxetine. Of the remaining 282 cases, 133 contained possible confounding factors (and were deemed to be possibly related), 146 presented too little information to assess, and three suggested atomoxetine as a probable cause of liver injuries. One of the three had a positive rechallenge. All three patients recovered after discontinuation of the drug.Conclusions: Since the launch of atomoxetine therapy, three spontaneously reported cases of reversible drug-induced liver injury were deemed probably related to it. Atomoxetine should be discontinued in patients with jaundice or laboratory evidence of liver injury and should not be restarted. [ABSTRACT FROM AUTHOR]

Objective: The present work examined suicide-related events in acute, double-blind, and placebo- or active comparator-controlled trials with atomoxetine.Method: Fourteen trials in pediatric patients were included. Potential events were identified in the adverse events database using a text-string search. Potential suicide-related events were categorized according to U.S. Food and Drug Administration-defined codes using blinded patient summaries. The meta-analyses used the Mantel-Haenszel incidence difference and Mantel-Haenszel risk ratio methods.Results: No patient in atomoxetine attention-deficit/hyperactivity disorder (ADHD) trials committed suicide. The frequency of suicidal ideation was 0.37% (5/1357) in pediatric patients taking atomoxetine versus 0% (0/851) for the placebo group; Mantel-Haenszel incidence difference of 0.46 (95% confidence interval 0.09-0.83; p =.016) and Mantel-Haenszel risk ratio of 2.92 (95% confidence interval 0.63-13.57; p =.172). Frequencies of suicide-related events in pediatric patients with ADHD did not differ between methylphenidate and atomoxetine treatments (Mantel-Haenszel incidence difference of -0.12 (95% confidence interval -0.62 to 0.38; p =.649). The number needed to harm in pediatric patients for an additional suicide-related event is 227 compared to the number needed to treat of five to achieve remission of ADHD symptoms.Conclusions: Although uncommon, suicidal ideation was significantly more frequent in pediatric ADHD patients treated with atomoxetine compared to those treated with placebo. Retrospective analysis has limitations in ascertaining intent. [ABSTRACT FROM AUTHOR]

BACKGROUND: The primary treatment for attention-deficit/hyperactivity disorder (ADHD) has been psychostimulants. Recently developed nonpsychostimulant treatments have allowed certain patients to switch from a psychostimulant to a nonpsychostimulant. However, the outcomes of such switches have not been systematically studied. OBJECTIVE: The purpose of this pilot study was to assess treatment tolerance and efficacy during a cross-taper transition from methylphenidate or amphetamine to atomoxetine among children and adolescents with ADHD. METHODS: This pilot study was conducted in patients (aged 6-17 years) with incomplete responses (failure to obtain full reduction/elimination of symptoms) or intolerance of adverse events (AEs) during psychostimulant treatment. Patients continued ongoing psychostimulant treatment during the first week of the study. Transition to atomoxetine began by administering atomoxetine 0.5 mg/kg . d plus full-dose psychostimulant for 1 week, followed in the second week by 1.2 mg/kg . d atomoxetine plus half-dose psychostimulant. Patients remained on 1.2 mg/kg . d atomoxetine monotherapy for the remaining 5 weeks. This stepwise transition was enacted due to the difference in pharmacodynamics between the psychostimulants and atomoxetine. Applying a stepwise cross-titration allowed for better control of ADHD symptoms during the intervening period. Change in ADHD symptoms, as measured by the mean change in the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-administered and -scored (ADHDRS-IV-Parent:Inv), was assessed from baseline to end point. RESULTS: Of the 62 subjects enrolled in the study, 39 (62.9%) were diagnosed as ADHD-combined type. Similar proportions were receiving methylphenidate (51.6%) and amphetamine (48.4%). Slightly more wished to switch due to inadequate response (53.2%) than intolerability (46.8%). Nine subjects discontinued at various times during the course of the study (patient or parent/caregiver decision [4], AE [2], protocol violation [2], and lack of efficacy [1]). Mean (SD) ADHDRS-IV-Parent:Inv total scores (n = 59, last-observation-carried-forward) improved significantly from baseline (visit 2) to an end point (32.1 [10.5] vs 22.6 [14.0]; P < 0.001). Of the 58 subjects answering in the atomoxetine monotherapy phase, 38 (65.5%) reported a preference for atomoxetine treatment over their previous psychostimulant. Tolerability results were as follows: 26 (44.1%) of 59 patients reported >or=1 AE, the most common being somnolence (4 [6.8%]), fatigue (3 [5.1%]), decreased appetite (3 [5.1%]), cough (3 [5.1%]), headache (3 [5.1%]), and contact dermatitis (2 [3.4%]). No clinically severe AEs were reported. Both mean (SD) diastolic (2.4 [7.8] mm Hg; P = 0.031) and systolic (2.4 [7.9] mm Hg; P = 0.029) blood pressures increased significantly from baseline to end point. Electrocardiography revealed a significant increase in mean (SD) heart rate (9.2 [11.6] bpm; P < 0.001) and a corresponding decrease in mean (SD) RR interval (-77.8 [98.2] ms; P < 0.001). Statistically significant, but mild, increases in diastolic pressure and heart rate were observed. CONCLUSION: These children and adolescent patients were successfully switched from methylphenidate or amphetamine to atomoxetine treatment, with resulting improvement in ADHD symptom severity from baseline in this pilot study. [ABSTRACT FROM AUTHOR]

Study Objectives: To determine whether obstructive sleep apnea (OSA) severity and/or biomarkers of inflammation/angiogenesis are associated with incident cancer in this clinical cohort., Methods: Consenting adult patients at the University of British Columbia Hospital between 2003 and 2014 completed a questionnaire about their medical history and sleep habits prior to undergoing a polysomnogram. Blood samples were collected the morning after polysomnography and processed for biomarkers of inflammation and angiogenesis. The clinical, polysomnography, and biomarker data were linked to the British Columbia Cancer Registry to ascertain incident cancer diagnoses. Cox proportional hazard regression was used to assess the association between OSA severity and biomarker concentrations with cancer risk., Results: A total of 1,990 patients were included in the analysis with a mean follow-up time of 12.8 years; 181 of them (9.1%) developed cancer after polysomnography. OSA severity was significantly associated with cancer risk after controlling for relevant covariates (hazard ratio = 1.08 per 10 events/h apnea-hypopnea index increase, confidence interval = 1.02-1.15, P = .015). In an exploratory analysis, 2 biomarkers were significantly associated with an increased cancer risk after controlling for relevant covariates (hazard ratio per interquartile range pg/mL increase of endostatin = 1.45, confidence interval = 1.12-1.87, P = .01 and hazard ratio for interquartile range pg/mL increase of vascular cell adhesion molecule-1 = 1.48, confidence interval = 1.04-2.11, P = .03, respectively)., Conclusions: OSA severity was an independent risk factor for cancer. Furthermore, 2 circulating markers were significantly associated with cancer risk. If these preliminary findings can be reproduced in other cohorts, biomarkers could potentially be used to prognosticate patients with OSA with respect to cancer risk., Citation: Hirsch Allen AJ, Kendzerska T, Bhatti P, et al. Obstructive sleep apnea severity, circulating biomarkers, and cancer risk. J Clin Sleep Med . 2024;20(9):1415-1422., (© 2024 American Academy of Sleep Medicine.)

Introducing a new Main Editor of JSR., (open access.)

Objectives: This research aimed to develop best-practice recommendations for identifying the "standard of care" (SoC) and integrate it when it is the comparator in diagnostic economic models (SoC comparator)., Methods: A multi-methods approach comprising 2 pragmatic literature reviews and 9 expert interviews was used. Experts rated their agreement with draft recommendations based on the authors' analysis of the reviews. These were refined iteratively to produce final recommendations., Results: Fourteen best-practice recommendations are provided. Care pathway mapping (using quantitative, qualitative, or mixed-methods approaches) should be used for identifying the SoC comparator. Guidelines analysis can be integrated with expert opinion to identify pathway variability and discrepancies from clinical practice. For integrating the SoC comparator into the model, recommendations around structure, input sourcing, data aggregation and reporting, input uncertainty, and model variability are presented. For example, modelers should consider that the reference standard is not synonymous with the SoC, and the SoC may not be the only comparator. The comparator limitations should be discussed with clinical experts, but elicitation of its diagnostic accuracy is not recommended. Probabilistic sensitivity analysis is recommended when evaluating the overall input uncertainty, and deterministic sensitivity analysis is useful when there is high model uncertainty or SoC variability. Consensus could not be reached for some topics (eg, the role of real-world data, model averaging, and alternative model structures), but the reported discussions provide points for consideration., Conclusions: To our knowledge, this is the first guidance to support modelers when identifying and operationalizing the SoC comparator in diagnostic cost-effectiveness models., Competing Interests: Author Disclosures Author disclosure forms can be accessed in the Supplemental Material section., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: Vaccination reduces the risk of acute coronavirus disease 2019 (COVID-19) in children, but it is less clear whether it protects against long COVID. We estimated vaccine effectiveness (VE) against long COVID in children aged 5 to 17 years., Methods: This retrospective cohort study used data from 17 health systems in the RECOVER PCORnet electronic health record program for visits after vaccine availability. We examined both probable (symptom-based) and diagnosed long COVID after vaccination., Results: The vaccination rate was 67% in the cohort of 1 037 936 children. The incidence of probable long COVID was 4.5% among patients with COVID-19, whereas diagnosed long COVID was 0.8%. Adjusted vaccine effectiveness within 12 months was 35.4% (95 CI 24.5-44.7) against probable long COVID and 41.7% (15.0-60.0) against diagnosed long COVID. VE was higher for adolescents (50.3% [36.6-61.0]) than children aged 5 to 11 (23.8% [4.9-39.0]). VE was higher at 6 months (61.4% [51.0-69.6]) but decreased to 10.6% (-26.8% to 37.0%) at 18-months., Conclusions: This large retrospective study shows moderate protective effect of severe acute respiratory coronavirus 2 vaccination against long COVID. The effect is stronger in adolescents, who have higher risk of long COVID, and wanes over time. Understanding VE mechanism against long COVID requires more study, including electronic health record sources and prospective data., (Copyright © 2024 by the American Academy of Pediatrics.)

Objectives: To develop preliminary good practice recommendations for synthesising and linking evidence of treatment effectiveness when modelling the cost-effectiveness of diagnostic tests., Methods: We conducted a targeted review of guidance from key Health Technology Assessment (HTA) bodies to summarise current recommendations on synthesis and linkage of treatment effectiveness evidence within economic evaluations of diagnostic tests. We then focused on a specific case study, the cost-effectiveness of troponin for the diagnosis of myocardial infarction, and reviewed the approach taken to synthesise and link treatment effectiveness evidence in different modelling studies., Results: The Australian and UK HTA bodies provided advice for synthesising and linking treatment effectiveness in diagnostic models, acknowledging that linking test results to treatment options and their outcomes is common. Across all reviewed models for the case study, uniform test-directed treatment decision making was assumed, i.e., all those who tested positive were treated. Treatment outcome data from a variety of sources, including expert opinion, were utilised for linked clinical outcomes. Preliminary good practice recommendations for data identification, integration and description are proposed., Conclusion: Modelling the cost-effectiveness of diagnostic tests poses unique challenges in linking evidence on test accuracy to treatment effectiveness data to understand how a test impacts patient outcomes and costs. Upfront consideration of how a test and its results will likely be incorporated into patient diagnostic pathways is key to exploring the optimal design of such models. We propose some preliminary good practice recommendations to improve the quality of cost-effectiveness evaluations of diagnostics tests going forward., (© 2024. The Author(s).)

Studies of dynamics on temporal networks often represent the network as a series of "snapshots," static networks active for short durations of time. We argue that successive snapshots can be aggregated if doing so has little effect on the overlying dynamics. We propose a method to compress network chronologies by progressively combining pairs of snapshots whose matrix commutators have the smallest dynamical effect. We apply this method to epidemic modeling on real contact tracing data and find that it allows for significant compression while remaining faithful to the epidemic dynamics.

Aims: When relying on clinical assessment alone, an estimated 22% of acute heart failure (AHF) patients are missed, so clinical guidelines recommend the use of N-terminal pro-B-type natriuretic peptide (NT-proBNP) for AHF diagnosis. Since publication of these guidelines, there has been poor uptake of NT-proBNP testing in part due to concerns over excessive false positive referrals resulting from the low specificity of a single 'rule-out' threshold of <300 pg/mL. Low specificity can be mitigated by the addition of age-specific 'rule-in' NT-proBNP thresholds., Methods and Results: A theoretical hybrid decision tree/semi-Markov model was developed, combining global trial and audit data to evaluate the cost-effectiveness of NT-proBNP testing using age-specific rule-in/rule-out (RI/RO) thresholds, compared with NT-proBNP RO only and with clinical decision alone (CDA). Cost-effectiveness was measured as the incremental cost per quality-adjusted life year (QALY) gained and incremental net health benefit. In the base case, using UK-specific inputs, NT-proBNP RI/RO was associated with both greater QALYs and lower costs than CDA. At a willingness-to-pay threshold of £20 000/QALY, NT-proBNP RO was also cost-effective compared with CDA [incremental cost-effectiveness ratio (ICER) of £8322/QALY], but not cost-effective vs. RI/RO (ICER of £64 518/QALY). Overall, NT-proBNP RI/RO was the most cost-effective strategy. Sensitivity and scenario analyses were undertaken; the conclusions were not impacted by plausible variations in parameters, and similar conclusions were obtained for the Netherlands and Spain., Conclusions: An NT-proBNP strategy that combines an RO threshold with age-specific RI thresholds provides a cost-effective alternative to the currently recommended NT-proBNP RO only strategy, achieving greater diagnostic specificity with minimal reduction in sensitivity and thus reducing unnecessary echocardiograms and hospital admissions., (© 2023 Roche Diagnostics Ltd and The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)