Managing common ambulatory conditions: Exploring clinical decision making performance between pharmacists and family physicians.

Background: Prescribing is part of the expanded scope of practice for pharmacists in Alberta, Canada. Given these responsibilities, clinical decision making (the outcome from the diagnostic and therapeutic decision making process) is an essential skill for pharmacists. The current study compared diagnostic and therapeutic decision-making between Additional Prescribing Authority (APA) pharmacists and family physicians using a set of common ambulatory clinical cases that both practitioners could encounter in the community as part of their daily practice. Objectives: To explore clinical decision making performance and behaviors between APA pharmacists and family physicians during the assessment and prescribing of common ambulatory conditions. Methods: Eight written ambulatory clinical cases were developed by a panel of experts in both family medicine and pharmacy that were commonly encountered in both professions' daily practice. Participating APA pharmacists and family physicians reviewed the cases and responded with likely diagnoses, recommended treatments, and reported confidence in therapeutic choices. The responses of 18 APA pharmacists and 9 family physicians in community practices were analyzed. Results: There were no significant differences in diagnostic accuracy, therapeutic accuracy, confidence in diagnostic choices, and confidence in therapeutic choices between APA pharmacists and family physicians to these common ambulatory presentations. Conclusions: This study provides preliminary insights regarding the capabilities of pharmacists in the assessment of common ambulatory community conditions and suggests that APA pharmacists are making similar diagnostic and therapeutic decisions to family physicians. Future research could focus on examining the performance of pharmacists trained in different pharmacy education models, as well as their ability to provide clinical assessment in other specialties, or in more uncommon clinical scenarios.

Using Machine Learning in Veterinary Medical Education: An Introduction for Veterinary Medicine Educators.

Machine learning (ML) offers potential opportunities to enhance the learning, teaching, and assessments within veterinary medical education including but not limited to assisting with admissions processes as well as student progress evaluations. The purpose of this primer is to assist veterinary educators in appraising and potentially adopting these rapid upcoming advances in data science and technology. In the first section, we introduce ML concepts and highlight similarities/differences between ML and classical statistics. In the second section, we provide a step-by-step worked example using simulated veterinary student data to answer a hypothesis-driven question. Python syntax with explanations is provided within the text to create a random forest ML prediction model, a model composed of decision trees with each decision tree being composed of nodes and leaves. Within each step of the model creation, specific considerations such as how to manage incomplete student records are highlighted when applying ML algorithms within the veterinary education field. The results from the simulated data demonstrate how decisions by the veterinary educator during ML model creation may impact the most important features contributing to the model. These results highlight the need for the veterinary educator to be fully transparent during the creation of ML models and future research is needed to establish guidelines for handling data not missing at random in medical education, and preferred methods for model evaluation.

Proregenerative extracellular matrix hydrogel mitigates pathological alterations of pelvic skeletal muscles after birth injury.

Pelvic floor disorders, including pelvic organ prolapse and urinary and fecal incontinence, affect millions of women globally and represent a major public health concern. Pelvic floor muscle (PFM) dysfunction has been identified as one of the leading risk factors for the development of these morbid conditions. Childbirth, specifically vaginal delivery, has been recognized as the most important potentially modifiable risk factor for PFM injury; however, the precise mechanisms of PFM dysfunction after parturition remain elusive. In this study, we demonstrated that PFMs exhibit atrophy and fibrosis in parous women with symptomatic pelvic organ prolapse. These pathological alterations were recapitulated in a preclinical rat model of simulated birth injury (SBI). The transcriptional signature of PFMs after injury demonstrated an impairment in muscle anabolism, persistent expression of genes that promote extracellular matrix (ECM) deposition, and a sustained inflammatory response. We also evaluated the administration of acellular injectable skeletal muscle ECM hydrogel for the prevention of these pathological alterations. Treatment of PFMs with the ECM hydrogel either at the time of birth injury or 4 weeks after injury mitigated PFM atrophy and fibrosis. By evaluating gene expression, we demonstrated that these changes are mainly driven by the hydrogel-induced enhancement of endogenous myogenesis, ECM remodeling, and modulation of the immune response. This work furthers our understanding of PFM birth injury and demonstrates proof of concept for future investigations of proregenerative biomaterial approaches for the treatment of injured pelvic soft tissues.

Pathologists aren't pigeons: exploring the neural basis of visual recognition and perceptual expertise in pathology.

Visual (perceptual) reasoning is a critical skill in many medical specialties, including pathology, diagnostic imaging, and dermatology. However, in an ever-compressed medical curriculum, learning and practicing this skill can be challenging. Previous studies (including work with pigeons) have suggested that using reward-feedback-based activities, novices can gain expert levels of visual diagnostic accuracy in shortened training times. But is this level of diagnostic accuracy a result of image recognition (categorization) or is it the acquisition of diagnostic expertise? To answer this, the authors measured electroencephalographic data (EEG) and two components of the human event-related brain potential (reward positivity and N170) to explore the nature of visual expertise in a novice-expert study in pathology visual diagnosis. It was found that the amplitude of the reward positivity decreased with learning in novices (suggesting a decrease in reliance on feedback, as in other studies). However, this signal remained significantly different from the experts whose reward positivity signal did not change over the course of the experiment. There were no changes in the amplitude of the N170 (a reported neural marker of visual expertise) in novices over time. Novice N170 signals remained statistically and significantly lower in amplitude compared to experts throughout task performance. These data suggest that, while novices gained the ability to recognize (categorize) pathologies through reinforcement learning as quantified by the change in reward positivity, increased accuracy, and decreased time for responses, there was little change in the neural marker associated with visual expertise (N170). This is consistent with the multi-dimensional and complex nature of visual expertise and provides insight into future training programs for novices to bridge the expertise gap.

Dicentric chromosome breakage in Drosophila melanogaster is influenced by pericentric heterochromatin and occurs in nonconserved hotspots.

Chromosome breakage plays an important role in the evolution of karyotypes and can produce deleterious effects within a single individual, such as aneuploidy or cancer. Forces that influence how and where chromosomes break are not fully understood. In humans, breakage tends to occur in conserved hotspots called common fragile sites (CFS), especially during replication stress. By following the fate of dicentric chromosomes in Drosophila melanogaster, we find that breakage under tension also tends to occur in specific hotspots. Our experimental approach was to induce sister chromatid exchange in a ring chromosome to generate a dicentric chromosome with a double chromatid bridge. In the following cell division, the dicentric bridges may break. We analyzed the breakage patterns of 3 different ring-X chromosomes. These chromosomes differ by the amount and quality of heterochromatin they carry as well as their genealogical history. For all 3 chromosomes, breakage occurs preferentially in several hotspots. Surprisingly, we found that the hotspot locations are not conserved between the 3 chromosomes: each displays a unique array of breakage hotspots. The lack of hotspot conservation, along with a lack of response to aphidicolin, suggests that these breakage sites are not entirely analogous to CFS and may reveal new mechanisms of chromosome fragility. Additionally, the frequency of dicentric breakage and the durability of each chromosome's spindle attachment vary significantly between the 3 chromosomes and are correlated with the origin of the centromere and the amount of pericentric heterochromatin. We suggest that different centromere strengths could account for this.

Comparative Pharmacokinetics and Injection Site Histopathology in Nude Mice Treated with Long-acting Buprenorphine Formulations.

Two long-acting formulations of buprenorphine are commercially available as analgesics for rodents. However, these drugs have not yet been studied in nude mice. We sought to investigate whether the manufacturer-recommended or labeled mouse doses of either drug would provide and sustain the purported therapeutic plasma concentration of buprenorphine (1 ng/mL) over 72 h in nude mice and to characterize the injection site histopathology. NU/NU nude and NU/+ heterozygous mice were subcutaneously injected with extended-release buprenorphine polymeric formulation (ER; 1 mg/kg), extendedrelease buprenorphine suspension (XR; 3.25 mg/kg), or saline (2.5 mL/kg). Plasma concentrations of buprenorphine were measured 6, 24, 48, and 72 h after injection. The injection site was examined histologically at 96 h after administration. XR dosing yielded significantly higher plasma buprenorphine concentrations than did ER dosing at every time point in both nude and heterozygous mice. No significant difference in plasma buprenorphine concentrations were detected between nude and heterozygous mice. Both formulations yielded plasma levels of buprenorphine of over 1 ng/mL at 6 h; XR sustained buprenorphine plasma levels above 1 ng/mL for over 48 h, whereas ER sustained this level for over 6 h. Injections sites of both formulations were characterized by a cystic lesion with a fibrous/fibroblastic capsule. ER induced more inflammatory infiltrates than did XR. This study indicates that while both XR and ER are suitable for use in nude mice, XR has a longer duration of likely therapeutic plasma levels and induces less subcutaneous inflammation at the injection site.

A highly predictive cardiac positron emission tomography (PET) risk score for 90-day and one-year major adverse cardiac events and revascularization.

BACKGROUND: With the increase in cardiac PET/CT availability and utilization, the development of a PET/CT-based major adverse cardiovascular events, including death, myocardial infarction (MI), and revascularization (MACE-Revasc) risk assessment score is needed. Here we develop a highly predictive PET/CT-based risk score for 90-day and one-year MACE-Revasc. METHODS AND RESULTS: 11,552 patients had a PET/CT from 2015 to 2017 and were studied for the training and development set. PET/CT from 2018 was used to validate the derived scores (n = 5049). Patients were on average 65 years old, half were male, and a quarter had a prior MI or revascularization. Baseline characteristics and PET/CT results were used to derive the MACE-Revasc risk models, resulting in models with 5 and 8 weighted factors. The PET/CT 90-day MACE-Revasc risk score trended toward outperforming ischemic burden alone [P = .07 with an area under the curve (AUC) 0.85 vs 0.83]. The PET/CT one-year MACE-Revasc score was better than the use of ischemic burden alone (P < .0001, AUC 0.80 vs 0.76). Both PET/CT MACE-Revasc risk scores outperformed risk prediction by cardiologists. CONCLUSION: The derived PET/CT 90-day and one-year MACE-Revasc risk scores were highly predictive and outperformed ischemic burden and cardiologist assessment. These scores are easy to calculate, lending to straightforward clinical implementation and should be further tested for clinical usefulness.

Exploring the development of interprofessional competence and professional identity: A Situated Learning Theory study.

Workplace-based learning provides medical students exposure to interprofessional competencies through repeated exposures and active participation in interprofessional learning activities. Using Situated Learning Theory as our theoretical lens, we explored with medical students how interacting with existing interprofessional teams contributes to development of an expanded health care professional identity. An embedded mixed methods study using semi-structured interviews and questionnaires to assess readiness for interprofessional learning was conducted with 14 medical students completing an elective at an interprofessional pain medicine clinic. Within this workplace-based context, a model identifying key themes and supporting factors contributing to the development of an extended professional identity was developed. These findings help describe the processes by which students gain interprofessional collaboration competence.

Intravascularly infused extracellular matrix as a biomaterial for targeting and treating inflamed tissues.

Decellularized extracellular matrix in the form of patches and locally injected hydrogels has long been used as therapies in animal models of disease. Here we report the safety and feasibility of an intravascularly infused extracellular matrix as a biomaterial for the repair of tissue in animal models of acute myocardial infarction, traumatic brain injury and pulmonary arterial hypertension. The biomaterial consists of decellularized, enzymatically digested and fractionated ventricular myocardium, localizes to injured tissues by binding to leaky microvasculature, and is largely degraded in about 3 d. In rats and pigs with induced acute myocardial infarction followed by intracoronary infusion of the biomaterial, we observed substantially reduced left ventricular volumes and improved wall-motion scores, as well as differential expression of genes associated with tissue repair and inflammation. Delivering pro-healing extracellular matrix by intravascular infusion post injury may provide translational advantages for the healing of inflamed tissues 'from the inside out'.

Chromosome Tug of War: Dicentric Chromosomes and the Centromere Strength Hypothesis.

It has been 70 years since the concept of varied centromere strengths was introduced based on the behavior of dicentric chromosomes. One of the key conclusions from those early experiments was that some centromeres could pull with sufficient force to break a dicentric chromosome bridge, while others could not. In the ensuing decades there have been numerous studies to characterize strengths of the various components involved, such as the spindle, the kinetochore, and the chromosome itself. We review these various measurements to determine if the conclusions about centromere strength are supported by current evidence, with special attention to characterization of Drosophila melanogaster kinetochores upon which the original conclusions were based.

Longitudinal assessment of competency development at The Ohio State University using the competency-based veterinary education (CBVE) model.

With the development of the American Association of Veterinary Medical Colleges' Competency-Based Veterinary Education (CBVE) model, veterinary schools are reorganizing curricula and assessment guidelines, especially within the clinical rotation training elements. Specifically, programs are utilizing both competencies and entrustable professional activities (EPAs) as opportunities for gathering information about student development within and across clinical rotations. However, what evidence exists that use of the central tenets of the CBVE model (competency framework, milestones and EPAs) improves our assessment practices and captures reliable and valid data to track competency development of students as they progress through their clinical year? Here, we report on validity evidence to support the use of scores from in-training evaluation report forms (ITERs) and workplace-based assessments of EPAs to evaluate competency progression within and across domains described in the CBVE, during the final year clinical training period of The Ohio State University's College of Veterinary Medicine (OSU-CVM) program. The ITER, used at the conclusion of each rotation, was modified to include the CBVE competencies that were assessed by identifying the stage of student development on a series of descriptive milestones (from pre-novice to competent). Workplace based assessments containing entrustment scales were used to assess EPAs from the CBVE model within each clinical rotation. Competency progression and entrustment scores were evaluated on each of the 31 rotations offered and high-stakes decisions regarding student performance were determined by a collective review of all the ITERs and EPAs recorded for each learner across each semester and the entire year. Results from the class of 2021, collected on approximately 190 students from 31 rotations, are reported with more than 55 299 total competency assessments combined with milestone placement and 2799 complete EPAs. Approximately 10% of the class was identified for remediation and received additional coaching support. Data collected longitudinally through the ITER on milestones provides initial validity evidence to support using the scores in higher stakes contexts such as identifying students for remediation and for determining whether students have met the necessary requirements to successfully complete the program. Data collected on entrustment scores did not, however, support such decision making. Implications are discussed.

Rational engineering of a synthetic insect-bacterial mutualism.

Many insects maintain mutualistic associations with bacterial endosymbionts, but little is known about how they originate in nature. In this study, we describe the establishment and manipulation of a synthetic insect-bacterial symbiosis in a weevil host. Following egg injection, the nascent symbiont colonized many tissues, including prototypical somatic and germinal bacteriomes, yielding maternal transmission over many generations. We then engineered the nascent symbiont to overproduce the aromatic amino acids tyrosine and phenylalanine, which facilitate weevil cuticle strengthening and accelerated larval development, replicating the function of mutualistic symbionts that are widely distributed among weevils and other beetles in nature. Our work provides empirical support for the notion that mutualistic symbioses can be initiated in insects by the acquisition of environmental bacteria. It also shows that certain bacterial genera, including the Sodalis spp. used in our study, are predisposed to develop these associations due to their ability to maintain benign infections and undergo vertical transmission in diverse insect hosts, facilitating the partner-fidelity feedback that is critical for the evolution of obligate mutualism. These experimental advances provide a new platform for laboratory studies focusing on the molecular mechanisms and evolutionary processes underlying insect-bacterial symbiosis.

What role does basic research have in an applied field?

Research in health professions education has often been portrayed as an applied field, one that draws on more basic forms of research in pursuing what are primarily practical ends. While there is an undeniable practical side to much of the work published in our field, and in this Journal in particular, this can be problematic when the necessary basic research is not extant. In this editorial, two of this Journal's editors consider some of the challenges in bridging these basic research gaps in an erstwhile applied field, and the implications for the kinds of research we undertake and for the identity of the field as a whole.

Building Clinical Skills Teaching Materials: A Study of Cognitive Task Analysis Versus Free Recall Instruction to Teach Canine Indirect Ophthalmoscopy.

Ophthalmoscopy is a core component of a complete ophthalmic examination. Due to its complex technical aspects and patients becoming uncooperative if the procedure is prolonged, it can be a difficult skill for a novice to learn and develop proficiency in. Skills instruction is typically provided by subject matter experts (SMEs) through free recall without an agreed-upon instructional framework. This can lead to unintentional omission of essential steps and knowledge required to perform skills correctly. Cognitive task analysis (CTA) allows for construction of standardized instructional protocols that encompass the knowledge and skills experts apply when performing tasks. The objectives of this study were to (a) develop a CTA-based teaching protocol for canine indirect ophthalmoscopy and (b) compare the steps verbalized or demonstrated by SMEs during free recall instruction versus those ultimately identified by CTA. Four SMEs participated in free recall instructional sessions and interviews used for the development of a CTA-based teaching protocol for novice learners. The CTA-based protocol identified 66 steps and sub-steps considered essential for successfully performing canine indirect ophthalmoscopy. During instructional sessions, SMEs on average failed to verbalize 57.1% of clinical knowledge steps, did not verbalize or demonstrate 68.3% and 9.5% of action steps, and did not verbalize or demonstrate 73.2% and 40.4% of decision steps, respectively. This study demonstrates that SMEs teaching indirect ophthalmoscopy by free recall may unintentionally omit important steps, suggesting that compared with free recall, CTA may generate more comprehensive and thus potentially more effective instructional materials for teaching technical skills in veterinary medicine.

Preventing post-surgical cardiac adhesions with a catechol-functionalized oxime hydrogel.

Post-surgical cardiac adhesions represent a significant problem during routine cardiothoracic procedures. This fibrous tissue can impair heart function and inhibit surgical access in reoperation procedures. Here, we propose a hydrogel barrier composed of oxime crosslinked poly(ethylene glycol) (PEG) with the inclusion of a catechol (Cat) group to improve retention on the heart for pericardial adhesion prevention. This three component system is comprised of aldehyde (Ald), aminooxy (AO), and Cat functionalized PEG mixed to form the final gel (Ald-AO-Cat). Ald-AO-Cat has favorable mechanical properties, degradation kinetics, and minimal swelling, as well as superior tissue retention compared to an initial Ald-AO gel formulation. We show that the material is cytocompatible, resists cell adhesion, and led to a reduction in the severity of adhesions in an in vivo rat model. We further show feasibility in a pilot porcine study. The Ald-AO-Cat hydrogel barrier may therefore serve as a promising solution for preventing post-surgical cardiac adhesions.

What Matters Most to Residency and Intern Selection Committees in Veterinary Medicine?

A recent survey of members of residency selection committees for the American College of Veterinary Internal Medicine and American College of Veterinary Surgeons boards found letters of recommendation to be the most important factor when reviewing a resident's application followed by class rank as the second most important factor. These statistics indicate an interesting, but possibly troubling trend. This Letter to The Editor discusses the major problems concerning these findings and what residency program committees might consider as an alternative.

Comparing Entrustment and Competence: An Exploratory Look at Performance-Relevant Information in the Final Year of a Veterinary Program.

Workplace-based assessments and entrustment scales have two primary goals: providing formative information to assist students with future learning; and, determining if and when learners are ready for safe, independent practice. To date, there has not been an evaluation of the relationship between these performance-relevant information pieces in veterinary medicine. This study collected quantitative and qualitative data from a single cohort of final-year students (n = 27) across in-training evaluation reports (ITERs) and entrustment scales in a distributed veterinary hospital environment. Here we compare progression in scoring and performance within and across student, within and across method of assessment, over time. Narrative comments were quantified using the Completed Clinical Evaluation Report Rating (CCERR) instrument to assess quality of written comments. Preliminary evidence suggests that we may be capturing different aspects of performance using these two different methods. Specifically, entrustment scale scores significantly increased over time, while ITER scores did not. Typically, comments on entrustment scale scores were more learner specific, longer, and used more of a coaching voice. Longitudinal evaluation of learner performance is important for learning and demonstration of competence; however, the method of data collection could influence how feedback is structured and how performance is ultimately judged.

Using Muse: Rapid Mobile Assessment of Brain Performance.

The advent of mobile electroencephalography (mEEG) has created a means for large scale collection of neural data thus affording a deeper insight into cognitive phenomena such as cognitive fatigue. Cognitive fatigue - a neural state that is associated with an increased incidence of errorful performance - is responsible for accidents on a daily basis which at times can cost human lives. To gain better insight into the neural signature of cognitive fatigue in the present study we used mEEG to examine the relationship between perceived cognitive fatigue and human-event related brain potentials (ERPs) and electroencephalographic (EEG) oscillations in a sample of 1,000 people. As a secondary goal, we wanted to further demonstrate the capability of mEEG to accurately measure ERP and EEG data. To accomplish these goals, participants performed a standard visual oddball task on an Apple iPad while EEG data were recorded from a Muse EEG headband. Counter to traditional EEG studies, experimental setup and data collection was completed in less than seven minutes on average. An analysis of our EEG data revealed robust N200 and P300 ERP components and neural oscillations in the delta, theta, alpha, and beta bands. In line with previous findings we observed correlations between ERP components and EEG power and perceived cognitive fatigue. Further, we demonstrate here that a linear combination of ERP and EEG features is a significantly better predictor of perceived cognitive fatigue than any ERP or EEG feature on its own. In sum, our results provide validation of mEEG as a viable tool for research and provide further insight into the impact of cognitive fatigue on the human brain.

Development of and Validity Evidence for a Canine Ocular Model for Training Novice Veterinary Students to Perform a Fundic Examination.

Indirect fundoscopy is challenging for novice learners, as patients are often intolerant of the procedure, impeding development of proficiency. To address this, we developed a canine ocular simulator that we hypothesized would improve student learning compared to live dogs. Six board-certified veterinary ophthalmologists and 19 second-year veterinary students (novices) performed an indirect fundic examination on the model and live dog. Prior to assessment, novices were introduced to the skill with a standardized teaching protocol and practiced (without feedback) with either the model (n = 10) or live dog (n = 9) for 30 minutes. All participants evaluated realism and usefulness of the model using a Likert-type scale. Performance on the live dog and model was evaluated in all participants using time to completion of task, performance of fundic examination using a checklist and global score, identification of objects in the fundus of the model, and evaluation of time spent looking at the fundus of the model using eye tracking. Novices (trained on simulator or live dogs) were compared in fundic examination performance on the live dog and identification of shapes in the model. In general, experts performed the fundic examination faster (p ≤ .0003) and more proficiently than the novices, although there were no differences in eye tracking behavior between groups (p ≥ .06). No differences were detected between training on simulator versus live dog in development of fundoscopy skills in novices (p ≥ .20). These findings suggest that this canine model may be an effective tool to train students to perform fundoscopy.