Physical and biophysical markers of assessment in medical training: A scoping review of the literature.

PURPOSE: Assessment in medical education has changed over time to measure the evolving skills required of current medical practice. Physical and biophysical markers of assessment attempt to use technology to gain insight into medical trainees' knowledge, skills, and attitudes. The authors conducted a scoping review to map the literature on the use of physical and biophysical markers of assessment in medical training. MATERIALS AND METHODS: The authors searched seven databases on 1 August 2022, for publications that utilized physical or biophysical markers in the assessment of medical trainees (medical students, residents, fellows, and synonymous terms used in other countries). Physical or biophysical markers included: heart rate and heart rate variability, visual tracking and attention, pupillometry, hand motion analysis, skin conductivity, salivary cortisol, functional magnetic resonance imaging (fMRI), and functional near-infrared spectroscopy (fNIRS). The authors mapped the relevant literature using Bloom's taxonomy of knowledge, skills, and attitudes and extracted additional data including study design, study environment, and novice vs. expert differentiation from February to June 2023. RESULTS: Of 6,069 unique articles, 443 met inclusion criteria. The majority of studies assessed trainees using heart rate variability (n = 160, 36%) followed by visual attention (n = 143, 32%), hand motion analysis (n = 67, 15%), salivary cortisol (n = 67, 15%), fMRI (n = 29, 7%), skin conductivity (n = 26, 6%), fNIRs (n = 19, 4%), and pupillometry (n = 16, 4%). The majority of studies (n = 167, 38%) analyzed non-technical skills, followed by studies that analyzed technical skills (n = 155, 35%), knowledge (n = 114, 26%), and attitudinal skills (n = 61, 14%). 169 studies (38%) attempted to use physical or biophysical markers to differentiate between novice and expert. CONCLUSION: This review provides a comprehensive description of the current use of physical and biophysical markers in medical education training, including the current technology and skills assessed. Additionally, while physical and biophysical markers have the potential to augment current assessment in medical education, there remains significant gaps in research surrounding reliability, validity, cost, practicality, and educational impact of implementing these markers of assessment.

Using big sequencing data to identify chronic SARS-Coronavirus-2 infections.

The evolution of SARS-Coronavirus-2 (SARS-CoV-2) has been characterized by the periodic emergence of highly divergent variants. One leading hypothesis suggests these variants may have emerged during chronic infections of immunocompromised individuals, but limited data from these cases hinders comprehensive analyses. Here, we harnessed millions of SARS-CoV-2 genomes to identify potential chronic infections and used language models (LM) to infer chronic-associated mutations. First, we mined the SARS-CoV-2 phylogeny and identified chronic-like clades with identical metadata (location, age, and sex) spanning over 21 days, suggesting a prolonged infection. We inferred 271 chronic-like clades, which exhibited characteristics similar to confirmed chronic infections. Chronic-associated mutations were often high-fitness immune-evasive mutations located in the spike receptor-binding domain (RBD), yet a minority were unique to chronic infections and absent in global settings. The probability of observing high-fitness RBD mutations was 10-20 times higher in chronic infections than in global transmission chains. The majority of RBD mutations in BA.1/BA.2 chronic-like clades bore predictive value, i.e., went on to display global success. Finally, we used our LM to infer hundreds of additional chronic-like clades in the absence of metadata. Our approach allows mining extensive sequencing data and providing insights into future evolutionary patterns of SARS-CoV-2.

GeNLP: a web tool for NLP-based exploration and prediction of microbial gene function.

SUMMARY: GeNLP is a web application that enables exploring microbial gene "semantics" and predictions of uncharacterized gene families based on their genomic context. It utilizes a pre-trained language model to uncover gene relationships and allows users to access and utilize the data as well as make their own predictions through an interactive interface. AVAILABILITY AND IMPLEMENTATION: The web application is accessible from all browsers at: http://gnlp.bursteinlab.org/. All source codes are freely available from GitHub under the MIT license here: https://github.com/burstein-lab/genomic-nlp-server.

Toward Efficient, Sustainable, and Scalable Methods of Treatment Characterization: An Investigation of Coding Clinical Practice from Chart Notes.

PURPOSE: Chart notes provide a low-cost data source that could help characterize what occurs in treatment with sufficient precision to improve management of care. This study assessed the interrater reliability of treatment content coded from chart notes and evaluated its concordance with content coded from transcribed treatment sessions. METHOD: Fifty randomly selected and digitally recorded treatment events were transcribed and coded for practice content. Independent coders then applied the same code system to chart notes for these same treatment events. ANALYSIS: We measured reliability and concordance of practice occurrence and extensiveness at two levels of specificity: practices (full procedures) and steps (subcomponents of those procedures). RESULTS: For chart notes, practices had moderate interrater reliability (M k = 0.50, M ICC = 0.56) and steps had moderate (M ICC = 0.74) to substantial interrater reliability (M k = 0.78). On average, 2.54 practices and 5.64 steps were coded per chart note and 4.53 practices and 13.10 steps per transcript. Across sources, ratings for 64% of practices and 41% of steps correlated significantly, with those with significant correlations generally demonstrating moderate concordance (practice M r = 0.48; step M r = 0.47). Forty one percent of practices and 34% of steps from transcripts were also identified in the corresponding chart notes. CONCLUSION: Chart notes provide an accessible data source for evaluating treatment content, with different levels of specificity posing tradeoffs for validity and reliability, which in turn may have implications for chart note interfaces, training, and new metrics to support accurate, reliable, and efficient measurement of clinical practice.

Protocol for randomized personalized trial for stress management compared to standard of care.

Stress is a significant public health burden in the United States, with most Americans reporting unhealthy levels of stress. Stress management techniques include various evidence-based treatments shown to be effective but with heterogeneous treatment responses, indicating a lack of uniform benefits for all individuals. Designed to assess a participant's response to a specific intervention, personalized (N-of-1) trials provide guidance for which treatment (s) work (s) best for the individual. Prior studies examining the effects of mindfulness meditation, yoga, and walking for stress reduction found all three interventions to be associated with significant reductions in self-reported measures of stress. Delivering these treatments using a personalized trial approach has the potential to assist clinicians in identifying the best stress management techniques for individuals with persistently high stress while fostering treatment decisions that consider their personal condition/barriers. This trial will evaluate a personalized approach compared to standard of care for three interventions (guided mindfulness meditation; guided yoga; and guided brisk walking) to manage perceived stress. Participants will respond to daily surveys and wear a Fitbit device for 18 weeks. After a 2-week baseline period, participants in the personalized trial groups will receive 12 weeks of interventions in randomized order, while participants in the standard-of-care group will have access to all interventions for self-directed stress management. After intervention, all participants will undergo 2 weeks of observation, followed by two additional weeks of the stress management intervention of their choosing while continuing outcome measurement. At study completion, all participants will be sent a satisfaction survey. The primary analysis will compare perceived stress levels between the personalized and standard of care arms. The results of this trial will provide further support for the use of personalized designs for managing stress. Clinical Trial Registration: clinicaltrials.gov, NCT05408832. Protocol version: 9/14/2022, 21-0968-MRB.

A Series of Personalized Virtual Light Therapy Interventions for Fatigue: Feasibility Randomized Crossover Trial for N-of-1 Treatment.

BACKGROUND: Fatigue is one of the most common symptoms treated in primary care and can lead to deficits in mental health and functioning. Light therapy can be an effective treatment for symptoms of fatigue; however, the feasibility, scalability, and individual-level heterogeneity of light therapy for fatigue are unknown. OBJECTIVE: This study aimed to evaluate the feasibility, acceptability, and effectiveness of a series of personalized (N-of-1) interventions for the virtual delivery of bright light (BL) therapy and dim light (DL) therapy versus usual care (UC) treatment for fatigue in 60 participants. METHODS: Participants completed satisfaction surveys comprising the System Usability Scale (SUS) and items assessing satisfaction with the components of the personalized trial. Symptoms of fatigue were measured using the Patient-Reported Outcomes Measurement Information System (PROMIS) daily, PROMIS weekly, and ecological momentary assessment (EMA) questionnaires delivered 3 times daily. Comparisons of fatigue between the BL, DL, and UC treatment periods were conducted using generalized linear mixed model analyses between participants and generalized least squares analyses within individual participants. RESULTS: Participants rated the usability of the personalized trial as acceptable (average SUS score=78.9, SD 15.6), and 92% (49/53) of those who completed satisfaction surveys stated that they would recommend the trial to others. The levels of fatigue symptoms measured using the PROMIS daily fatigue measure were lower or improved in the BL (B=-1.63, 95% CI -2.63 to -0.63) and DL (B=-1.44, 95% CI -2.50 to -0.38) periods relative to UC. The treatment effects of BL and DL on the PROMIS daily measure varied among participants. Similar findings were demonstrated for the PROMIS weekly and EMA measures of fatigue symptoms. CONCLUSIONS: The participant scores on the SUS and satisfaction surveys suggest that personalized N-of-1 trials of light therapy for fatigue symptoms are both feasible and acceptable. Both interventions produced significant (P<.05) reductions in participant-reported PROMIS and EMA fatigue symptoms relative to UC. However, the heterogeneity of these treatment effects across participants indicated that the effect of light therapy was not uniform. This heterogeneity along with high ratings of usability and satisfaction support the use of personalized N-of-1 research designs in evaluating the effect of light therapy on fatigue for each patient. Furthermore, the results of this trial provide additional support for the use of a series of personalized N-of-1 research trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT04707846; https://clinicaltrials.gov/ct2/show/NCT04707846.

A Series of Remote Melatonin Supplement Interventions for Poor Sleep: Protocol for a Feasibility Pilot Study for a Series of Personalized (N-of-1) Trials.

BACKGROUND: Poor sleep, defined as short-duration or poor-quality sleep, is a frequently reported condition with many deleterious effects including poorer cognitive functioning, increased accidents, and poorer health. Melatonin has been shown to be an efficacious treatment to manage symptoms of poor sleep. However, the treatment effects of melatonin on sleep can vary greatly between participants. Personalized, or N-of-1, trial designs represent a method for identifying the best treatment for individual participants. Although using N-of-1 trials of melatonin to treat poor sleep is possible, the feasibility, acceptability, and effectiveness of N-of-1 trials using melatonin are unknown. Using the National Institutes of Health Stage Model for Behavioral Intervention Development, a stage IB (intervention refinement, modification, and adaptation and pilot testing) design appeared to be needed to address these feasibility questions. OBJECTIVE: This trial series evaluates the feasibility, acceptability, and effectiveness of a series of personalized interventions for remote delivery of melatonin dose (3 and 0.5 mg) versus placebo supplements for self-reported poor sleep among 60 participants. The goal of this study is to provide valuable information about implementing remote N-of-1 randomized controlled trials to improve poor sleep. METHODS: Participants will complete a 2-week baseline followed by six 2-week alternating intervention periods of 3 mg of melatonin, 0.5 mg of melatonin, and placebo. Participants will be randomly assigned to 2 intervention orders. The feasibility and acceptability of the personalized trial approach will be determined with participants' ratings of usability and satisfaction with the remote, personalized intervention delivery system. The effectiveness of the intervention will be measured using participants' self-reported sleep quality and duration and Fitbit tracker-measured sleep duration and efficiency. Additional measures will include ecological momentary assessment measures of fatigue, stress, pain, mood, concentration, and confidence as well as measures of participant adherence to the intervention, use of the Fitbit tracker, and survey data collection. RESULTS: As of the submission of this protocol, recruitment for this National Institutes of Health stage IB personalized trial series is approximately 78.3% complete (47/60). We expect recruitment and data collection to be finalized by June 2023. CONCLUSIONS: Evaluating the feasibility, acceptability, and effectiveness of a series of personalized interventions of melatonin will address the longer term aim of this program of research-is integrating N-of-1 trials useful patient care? The personalized trial series results will be published in a peer-reviewed journal and will follow the CONSORT (Consolidated Standards of Reporting Trials) extension for N-of-1 trials (CENT 2015) reporting guidelines. This trial series was approved by the Northwell Health institutional review board. TRIAL REGISTRATION: ClinicalTrials.gov NCT05349188; https://www.clinicaltrials.gov/study/NCT05349188. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/45313.

Cephalosporins for the treatment of uncomplicated pyelonephritis: A systematic review.

BACKGROUND: The 2011 Infectious Diseases Society of America and European Society of Clinical Microbiology and Infectious Diseases guidelines recommend ciprofloxacin or sulfamethoxazole-trimethoprim (SMX-TMP) as first-line agents to treat uncomplicated acute pyelonephritis (APN). OBJECTIVE: With increasing antimicrobial resistance rates and recent changes in practice patterns, the objective of this systematic review was to describe the effectiveness of cephalosporins for uncomplicated APN in more recently published literature. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used for reporting. We searched PubMed, Embase, and Scopus for publications between January 2010 and September 2022. Eligible articles detailed patients with uncomplicated APN, treated with first- to fourth-generation cephalosporins, and identified a clinical, microbiological, or health care utilization outcome. Studies with more than 30% of complicated APN patients, non-English-language studies, case reports, case series, pharmacodynamic or pharmacokinetic studies, and in vitro laboratory or animal studies were excluded. Screening, review, and extraction were performed independently by 2 researchers, plus a third for conflict resolution. Critical appraisal of studies was performed using Joanna Briggs Institute checklists. RESULTS: Eight studies met inclusion, including 5 cohort studies (62.5%), 2 randomized controlled trials (25%), and 1 nonrandomized experimental study (12.5%). Cephalosporins most used across the studies included cefazolin, cephalexin, cefuroxime, cefotaxime, cefdinir, cefditoren, and ceftriaxone. Outcomes assessed were diverse, including clinical or microbiological success and time to defervescence or symptom resolution. Cephalosporins displayed effectiveness for the treatment of acute uncomplicated APN regardless of study design or the presence of a comparison group. No trials reported inferiority of clinical treatment outcomes compared with a fluoroquinolone or SMX-TMP. CONCLUSION: Cephalosporins may be viable treatment options for the management of uncomplicated APN.

Beyond diversity and inclusion: Developing a research agenda for anti-racism in emergency medicine education.

Background: Addressing racism in emergency medicine education is vital for providing optimal training and assessment of physicians in the specialty, developing physicians with the skills necessary to advocate for their patients, and recruiting and retaining a diverse group of physicians. To form a prioritized research agenda, the Society of Academic Emergency Medicine (SAEM) conducted a consensus conference at the annual meeting in May 2022 on addressing racism in emergency medicine, which included a subgroup on education. Methods: The education workgroup worked on summarizing the current literature on addressing racism in emergency medicine education, identifying critical knowledge gaps, and creating a consensus-driven research agenda for addressing racism in emergency medicine education. We used a nominal group technique and modified Delphi to develop priority questions for research. We then distributed a pre-conference survey to conference registrants to rate priority areas for research. During the consensus conference, group leaders provided an overview and background describing the rationale for the preliminary research question list. Attendees were then involved in discussions to help modify and develop research questions. Results: Nineteen questions were initially selected by the education workgroup as potential areas for research. The education workgroup's next round of consensus building resulted in a consensus of ten questions to be included in the pre-conference survey. No questions in the pre-conference survey reached consensus. After robust discussion and voting by workgroup members and attendees at the consensus conference, six questions were determined to be priority research areas. Conclusions: We believe recognizing and addressing racism in emergency medicine education is imperative. Critical gaps in curriculum design, assessment, bias training, allyship, and the learning environment negatively impact training programs. These gaps must be prioritized for research as they can have adverse effects on recruitment, the ability to promote a safe learning environment, patient care, and patient outcomes.

Oil-Water Separation using Synthetic Trees.

Existing oil-water filtration techniques require gravity or a pump as the driving force for separation. Here, we demonstrate transpiration-powered oil-water filtration using a synthetic tree, which operates pumplessly and against gravity. From top to bottom, our synthetic tree was composed of: a nanoporous "leaf" to generate suction via evaporation, a vertical array of glass tubes serving as the tree's xylem conduits, and filters attached to the tube inlets to act as the oil-excluding roots. When placing the tree in an oil emulsion bath, filtrate samples were measured to be 97-98% pure water using gravimetry and refractometry. The spontaneous oil-water separation offered by synthetic trees could be useful for applications such as oil spill cleanup, wastewater purification, and oil extraction.

Extensive Characterization of Polysorbate 80 Oxidative Degradation Under Stainless Steel Conditions.

Polysorbate-80 (PS-80) is a common surfactant used in biologics formulations. However, the tendency of oxidation to PS-80 when exposed to stainless steel surfaces brings various challenges during manufacturing processes, such as inconsistent shelf-life of PS-80 solutions, which can further impact the biologics and vaccines production. In this work, the root causes of PS-80 oxidation when in contact with stainless steel conditions were thoroughly investigated through the use of various complementary analytical techniques including U/HPLC-CAD, LC-MS, ICP-MS, peroxide assay, and EPR spectroscopy. The analytical tool kit used in this work successfully revealed a PS-80 degradation mechanism from the perspective of PS-80 content, PS-80 profile, iron content, peroxide production, and radical species. The combined datasets reveal that PS-80 oxidative degradation occurs in the presence of histidine and iron in addition to being combined with the hydroperoxides in PS-80 material. The oxidative pathway and potential degradants were identified by LC-MS. The PS-80 profile based on the U/HPLC-CAD assay provided an effective way to identify early-signs of PS-80 degradation. The results from a peroxide assay observed increased hydroperoxide along with PS-80 degradation. EPR spectra confirmed the presence of histidine-related radicals during PS-80 oxidation identifying how histidine is involved in the oxidation. All assays and findings introduced in this work will provide insight into how PS-80 oxidative degradation can be avoided, controlled, or detected. It will also provide valuable evaluations on techniques that can be used to identify PS-80 degradation related events that occur during the manufacturing process.

Filling the Core EPA 10 assessment void: A framework for individual assessment of Core Entrustable professional activity 10 competencies in medical students.

Objectives: The goal of this study was to develop and evaluate a novel curriculum and assessment tool for Core Entrustable Professional Activity (EPA) 10 competencies and entrustment scoring in a cohort of medical students in their emergency medicine (EM) clerkship using a framework of individualized, ad hoc, formative assessment. Core EPA 10 is an observable workplace-based activity for graduating medical students to recognize a patient requiring urgent or emergent care and initiate evaluation and management. Methods: This is a prospective, pretest-posttest study of medical students during their EM clerkship. Using the Thomas and Kern framework, we created a curriculum of simulation cases about chest pain/cardiac arrest and respiratory distress, which included novel assessment checklists, and instructional videos about recognizing and managing emergencies. Students were individually pretested on EPA 10 competencies using the simulation cases. Two raters scored students using standardized checklists. Students then watched instructional videos, underwent a posttest with the simulation cases, and were scored again by the two raters using the checklists. Differences between pretest and posttest scores were analyzed using paired t-tests and Wilcoxon signed-rank tests. Results: Seventy-three out of 85 (86%) students completed the curriculum. Mean scores from pretest to final posttest in the chest pain/cardiac arrest and respiratory distress cases significantly improved from 14.8/19 (SD 1.91), to 17.1/19 (SD = 1.00), t(68) = 10.56, p < 0.001, and 8.5/13 (SD 1.79), to 11.1/13(SD 0.89), t(67) = 11.15, p < 0.001, respectively. The kappa coefficients were 0.909 (n = 2698, p < 0.001) and 0.931 (n = 1872, p < 0.001). Median modified Chen entrustment scores improved from 1b (i.e., "Watch me do this") to 2b (i.e., "I'll watch you") for the chest pain/cardiac arrest case (p < 0.001) and 1b/2a (i.e., "Watch me do this"/ "Let's do this together") to 3a (i.e. "You go ahead, and I'll double-check all of your findings") for the respiratory distress case (p < 0.001). Conclusion: A new directed curriculum of standardized simulation cases and asynchronous instructional videos improved medical student performance in EPA 10 competencies and entrustment scores. This study provides a curricular framework to support formative individualized assessments for EPA 10.

Series of virtual light therapy interventions for fatigue: a feasibility pilot study protocol for a series of personalised (N-of-1) trials.

INTRODUCTION: Fatigue is one of the most commonly recorded patient symptoms that can result in deficits in aspects of psychomotor functioning, cognition, work performance and mood. Research shows that bright light and dim light therapy may be an efficacious way to reduce symptoms of fatigue. Still, the feasibility, scalability, individual treatment effects and adverse event heterogeneity of these treatments are unknown. METHODS AND ANALYSIS: The current study evaluates the feasibility, acceptability and effectiveness of a series of personalised (N-of-1) interventions for virtual delivery of bright light therapy and dim light therapy versus usual care treatment for fatigue in 60 participants. We hypothesise that this study will provide valuable information about implementing virtual, N-of-1 randomised controlled trials (RCTs) for fatigue. It will also offer results about determining participants' ratings of usability and satisfaction with the virtual, personalised intervention delivery system; evaluating participants' improvement of fatigue symptoms; and, in the long term, identify ways to integrate N-of-1 light therapy trials into patient care. ETHICS AND DISSEMINATION: This trial was approved by the Northwell Health Institutional Review Board. The trial results will be published in a peer-reviewed journal. All publications resulting from this series of personalised trials will follow the Consolidated Standards of Reporting Trials extension for N-of-1 trials CENT 2015 reporting guidelines. REGISTRATION DETAILS: This trial is registered in www. CLINICALTRIALS: gov (number NCT04707846). TRIAL REGISTRATION NUMBER: NCT04707846.

Ethnic and Racial Differences in Ratings in the Medical Student Standardized Letters of Evaluation (SLOE).

Background: The Standardized Letter of Evaluation (SLOE) stratifies the assessment of emergency medicine (EM) bound medical applicants. However, bias in SLOE, particularly regarding race and ethnicity, is an underexplored area. Objective: This study aims to assess whether underrepresented in medicine (UIM) and non-UIM applicants are rated differently in SLOE components. Methods: This was a cross-section study of EM-bound applicants across 3 geographically distinct US training programs during the 2019-2020 application cycle. Using descriptive and regression analyses, we examine the differences between UIM applicants and non-UIM applicants for each of the SLOE components: 7 qualifications of an EM physician (7QEM), global assessment (GA) rating, and projected rank list (RL) position. Results: Out of a combined total of 3759, 2002 (53.3%) unique EM-bound applicants were included. UIM applicants had lower ratings for each of the 7QEM questions, GA, and RL positions. Compared to non-UIM applicants, only some of the 7QEM components: "Work ethic and ability to assume responsibility," "Ability to work in a team, and "Ability to communicate a caring nature," were associated with their SLOE. "Commitment to EM" correlated more with GA for UIM than for non-UIM applicants. Conclusions: This study shows a difference in SLOE rating, with UIM applicants receiving lower ratings than non-UIM applicants.

Deciphering microbial gene function using natural language processing.

Revealing the function of uncharacterized genes is a fundamental challenge in an era of ever-increasing volumes of sequencing data. Here, we present a concept for tackling this challenge using deep learning methodologies adopted from natural language processing (NLP). We repurpose NLP algorithms to model "gene semantics" based on a biological corpus of more than 360 million microbial genes within their genomic context. We use the language models to predict functional categories for 56,617 genes and find that out of 1369 genes associated with recently discovered defense systems, 98% are inferred correctly. We then systematically evaluate the "discovery potential" of different functional categories, pinpointing those with the most genes yet to be characterized. Finally, we demonstrate our method's ability to discover systems associated with microbial interaction and defense. Our results highlight that combining microbial genomics and language models is a promising avenue for revealing gene functions in microbes.

Drivers of adaptive evolution during chronic SARS-CoV-2 infections.

In some immunocompromised patients with chronic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, considerable adaptive evolution occurs. Some substitutions found in chronic infections are lineage-defining mutations in variants of concern (VOCs), which has led to the hypothesis that VOCs emerged from chronic infections. In this study, we searched for drivers of VOC-like emergence by consolidating sequencing results from a set of 27 chronic infections. Most substitutions in this set reflected lineage-defining VOC mutations; however, a subset of mutations associated with successful global transmission was absent from chronic infections. We further tested the ability to associate antibody evasion mutations with patient-specific and virus-specific features and found that viral rebound is strongly correlated with the emergence of antibody evasion. We found evidence for dynamic polymorphic viral populations in most patients, suggesting that a compromised immune system selects for antibody evasion in particular niches in a patient's body. We suggest that a tradeoff exists between antibody evasion and transmissibility and that extensive monitoring of chronic infections is necessary to further understanding of VOC emergence.