Twelve tips for improving the quality of assessor judgements in senior medical student clinical assessments.

Assessment of senior medical students is usually calibrated at the level of achieving expected learning outcomes for graduation. Recent research reveals that clinical assessors often balance two slightly different perspectives on this benchmark. The first is the formal learning outcomes at graduation, ideally as part of a systematic, program-wide assessment approach that measures learning achievement, while the second is consideration of the candidate's contribution to safe care and readiness for practice as a junior doctor. The second is more intuitive to the workplace, based on experience working with junior doctors. This perspective may enhance authenticity in assessment decisions made in OSCEs and work-based assessments to better align judgements and feedback with professional expectations that will guide senior medical students and junior doctors' future career development. Modern assessment practices should include consideration of qualitative as well as quantitative information, overtly including perspectives of patients, employers, and regulators. This article presents 12 tips for how medical education faculty might support clinical assessors by capturing workplace expectations of first year medical graduates and develop graduate assessments based on a shared heuristic of 'work-readiness'. Peer-to-peer assessor interaction should be facilitated to achieve correct calibration that 'merges' the differing perspectives to produce a shared construct of an acceptable candidate.

Examiners' decision-making processes in observation-based clinical examinations.

BACKGROUND: Objective structured clinical examinations (OSCEs) are commonly used to assess the clinical skills of health professional students. Examiner judgement is one acknowledged source of variation in candidate marks. This paper reports an exploration of examiner decision making to better characterise the cognitive processes and workload associated with making judgements of clinical performance in exit-level OSCEs. METHODS: Fifty-five examiners for exit-level OSCEs at five Australian medical schools completed a NASA Task Load Index (TLX) measure of cognitive load and participated in focus group interviews immediately after the OSCE session. Discussions focused on how decisions were made for borderline and clear pass candidates. Interviews were transcribed, coded and thematically analysed. NASA TLX results were quantitatively analysed. RESULTS: Examiners self-reported higher cognitive workload levels when assessing a borderline candidate in comparison with a clear pass candidate. Further analysis revealed five major themes considered by examiners when marking candidate performance in an OSCE: (a) use of marking criteria as a source of reassurance; (b) difficulty adhering to the marking sheet under certain conditions; (c) demeanour of candidates; (d) patient safety, and (e) calibration using a mental construct of the 'mythical [prototypical] intern'. Examiners demonstrated particularly higher mental demand when assessing borderline compared to clear pass candidates. CONCLUSIONS: Examiners demonstrate that judging candidate performance is a complex, cognitively difficult task, particularly when performance is of borderline or lower standard. At programme exit level, examiners intuitively want to rate candidates against a construct of a prototypical graduate when marking criteria appear not to describe both what and how a passing candidate should demonstrate when completing clinical tasks. This construct should be shared, agreed upon and aligned with marking criteria to best guide examiner training and calibration. Achieving this integration may improve the accuracy and consistency of examiner judgements and reduce cognitive workload.

Activator protein-1 and caspase 8 mediate p38α MAPK-dependent cardiomyocyte apoptosis induced by palmitic acid.

Lipoapoptosis of cardiomyocytes may underlie diabetic cardiomyopathy. Numerous forms of cardiomyopathies share a common end-pathway in which apoptotic loss of cardiomyocytes is mediated by p38α mitogen activated protein kinase (MAPK). Although we have previously shown that palmitic acid (PA), a saturated fatty acid (SFA) elevated in plasma of type 2 diabetes mellitus and morbid obesity, induces apoptosis in cardiomyocytes via p38α MAPK-dependent signaling, the downstream cascade events that cause cell death remain unknown. The objective of this study was to investigate mechanisms involved in palmitic acid-induced cardiomyocyte apoptosis. Human adult ventricular cardiomyocyte line (AC16 cells) exposed to high physiological levels of PA for 16 h showed enhanced transcription and phosphorylation of c-fos and c-jun subunits of AP-1 and transcription of caspase 8. When AC16 cells were transfected with small interfering RNA specific against p38α MAPK (si-p38α) for 24 or 48 h, the amplified phosphorylation of c-fos was dose-dependently attenuated, and procaspase 8 was dose-dependently reduced. With translational knockdown of c-fos, PA-induced apoptosis was diminished. Inhibition of caspase 8 for 24 h reduced apoptosis in PA-treated cardiomyocytes. These findings provide evidence for induction of apoptosis in cardiomyocytes exposed to high SFA by a novel pathway requiring activation of c-fos/AP-1 and caspase 8. These results demonstrate how elevated plasma SFA may lead to continual and cumulative loss of cardiomyocytes and potentially contribute to the development of diabetic cardiomyopathy.

A snapshot of current Objective Structured Clinical Examination (OSCE) practice at Australian medical schools.

Objective: The objective of this collaborative study was to compare current practices of conducting high-stake, exit-level Objective Structured Clinical Examinations (OSCEs) at all Australian medical schools. We aimed to document similarities and differences between schools, and compare existing practice against available gold standard, evidence-based practice. We also aimed to identify areas where gold standards do not currently exist, and could be developed in the future. Methods: A 72-item semi-structured questionnaire was sent to all 19 Australian medical schools with graduating students. Results: A total of 18/19 schools responded. Of these, 16/18 schools had summative exit-level OSCEs representing content from multiple medical specialties. The total number of OSCE stations varied from 8 to 16, with total OSCE testing time ranging from 70 to 160 min. All schools blueprinted their OSCE to their curriculum, and trained simulated patients and examiners. There was variation in the format of marking rubric used. Conclusions: This study has provided insight into the current OSCE practices of the majority of medical schools in Australia. Whilst the comparative data reveal a wide variation in OSCE practices between schools, many recommended "gold standard" OSCE practices are implemented. The collective awareness of our similarities and differences provides us with a baseline platform, as well as an impetus for iterative quality improvement. Such discourse also serves to develop new gold standards in practice where none have previously existed.

Effect of liraglutide on dietary lipid-induced insulin resistance in humans.

AIMS: To test whether liraglutide suppresses postprandial elevations in lipids and thus protects against high saturated fatty acid (SFA) diet-induced insulin resistance. METHODS: In a randomized placebo-controlled crossover study, 32 participants with normal or mildly impaired glucose tolerance received liraglutide and placebo for 3 weeks each. Insulin suppression tests (IST) were conducted at baseline and after a 24-hour SFA-enriched diet after each treatment. Plasma glucose, insulin, triglycerides and non-esterified fatty acids (NEFA) were measured over the initial 8 hours (breakfast and lunch) on the SFA diet. A subset of participants underwent ex vivo measurements of insulin-mediated vasodilation of adipose tissue arterioles and glucose metabolism regulatory proteins in skeletal muscle. RESULTS: Liraglutide reduced plasma glucose, triglycerides and NEFA concentrations during the SFA diet (by 50%, 25% and 9%, respectively), and the SFA diet increased plasma glucose during the IST (by 36%; all P < .01 vs placebo). The SFA diet-induced impairment of vasodilation on placebo (-9.4% vs baseline; P < .01) was ameliorated by liraglutide (-4.8%; P = .1 vs baseline). In skeletal muscle, liraglutide abolished the SFA-induced increase in thioredoxin-interacting protein (TxNIP) expression (75% decrease; P < .01 vs placebo) and increased 5'AMP-activated protein kinase (AMPK) phosphorylation (50% vs -3%; P = .04 vs placebo). CONCLUSIONS: Liraglutide blunted the SFA-enriched diet-induced peripheral insulin resistance. This effect may be related to improved microvascular function and modulation of TxNIP and AMPK pathways in skeletal muscle.

A collaborative comparison of objective structured clinical examination (OSCE) standard setting methods at Australian medical schools.

BACKGROUND: A key issue underpinning the usefulness of the OSCE assessment to medical education is standard setting, but the majority of standard-setting methods remain challenging for performance assessment because they produce varying passing marks. Several studies have compared standard-setting methods; however, most of these studies are limited by their experimental scope, or use data on examinee performance at a single OSCE station or from a single medical school. This collaborative study between 10 Australian medical schools investigated the effect of standard-setting methods on OSCE cut scores and failure rates. METHODS: This research used 5256 examinee scores from seven shared OSCE stations to calculate cut scores and failure rates using two different compromise standard-setting methods, namely the Borderline Regression and Cohen's methods. RESULTS: The results of this study indicate that Cohen's method yields similar outcomes to the Borderline Regression method, particularly for large examinee cohort sizes. However, with lower examinee numbers on a station, the Borderline Regression method resulted in higher cut scores and larger difference margins in the failure rates. CONCLUSION: Cohen's method yields similar outcomes as the Borderline Regression method and its application for benchmarking purposes and in resource-limited settings is justifiable, particularly with large examinee numbers.

Improving assessment practice through cross-institutional collaboration: An exercise on the use of OSCEs.

BACKGROUND: This study was undertaken to improve assessment practice on OSCEs through collaboration across geographically dispersed medical schools in Australia. METHODS: A total of eleven OSCE stations were co-developed by four medical schools and used in summative 2011 and 2012 examinations for the assessment of clinical performance in the early clinical and exit OSCEs in each school's medical course. Partial Credit Rasch Model was used to evaluate the psychometric properties of the shared OSCE data. Evaluation of the quality assurance reports was used to determine the beneficial impact of the collaborative benchmarking exercise on learning and teaching outcomes. RESULTS: The data for each examination demonstrated sufficient fit to the Rasch model with infit mean square values ranging from 0.88 to 0.99. Person separation (1.25-1.63) indices indicated good reliability. Evaluation of perceived benefits showed that the benchmarking process was successful as it highlighted common curriculum areas requiring specific focus and provided comparable data on the quality of teaching at the participating medical schools. CONCLUSION: This research demonstrates the validity of the psychometric data and benefits of evaluating clinical competence across medical schools without the enforcement of a prescriptive national curriculum or assessment.

Sex Disparities in Operating Room use Among Cataract Surgeons: A 10-Year Retrospective Population-Based Analysis.

PURPOSE: To evaluate sex differences in operating room (OR) time and case volumes among comprehensive cataract surgeons in Ontario, Canada's most populated province. DESIGN: Retrospective, population-based cohort study. METHODS: Physician billing data of active comprehensive cataract surgeons between 2010 and 2019 were analyzed to identify all cataract surgeries in this timeframe. The number of OR days and case volume were the primary outcomes. Data were stratified by surgeon sex and career stage. RESULTS: Between 2010 and 2019, approximately 1.05 million cataract surgeries were performed in Ontario. There were an average of 195 ± 3 comprehensive cataract surgeons per year, of which 39 ± 5 were female. The proportion of female surgeons increased from 16.8% of all surgeons in 2010 to 24.4% in 2019. The greatest proportion of male surgeons were in the late phase of their career, whereas the greatest proportion of female surgeons were in the early stage of their career. On average, male surgeons had 44.9 ± 1.90 OR days per year and females had 32 ± 1.90 OR days per year, resulting in female surgeons averaging 12.45 ± 1.90 fewer OR days per year. This OR distribution remained consistent across career stages. Average case volumes per OR day were similar across sexes, but male surgeons performed on average 172.7 ± 30.6 more surgeries per year. CONCLUSIONS: Despite performing similar average case volumes per OR day, female surgeons had less OR time compared to their male counterparts per year, and this remained consistent across career stages and over the 10-year period. Metrics for OR allocation and use should be well defined and transparent.

GRK2-mediated inhibition of adrenergic and dopaminergic signaling in right ventricular hypertrophy: therapeutic implications in pulmonary hypertension.

BACKGROUND: The cause and consequences of impaired adrenergic signaling in right ventricular failure/hypertrophy (RVH) are poorly understood. We hypothesized that G protein-coupled receptor kinase-2 (GRK2)-mediated uncoupling of ß-adrenergic receptor signaling impairs inotropic reserve. The implications of right ventricular (RV) adrenergic remodeling for inotrope selection and the therapeutic benefit of interrupting Gßγ-GRK2 interaction, using gallein, were tested. METHODS AND RESULTS: Chamber-specificity and cellular localization of adrenergic remodeling were compared in rodent RVH associated with pulmonary arterial hypertension (PAH-RVH; SU5416+chronic-hypoxia or Monocrotaline) versus pulmonary artery banding-induced RVH (PAB-RVH). Results were corroborated in RV arrays from 10 PAH patients versus controls. Inotropic reserve was assessed in RV- and left ventricular-Langendorff models and in vivo. Gallein therapy (1.8 mg/kg/day ×2-weeks) was assessed. Despite similar RVH, cardiac output (58.3±4.9 versus 82.9±4.8 mL/min; P<0.001) and treadmill distance (41.5±11.6 versus 244.1±12.4 m; P<0.001) were lower in PAH-RVH versus PAB-RVH. In PAH-RVH versus PAB-RVH there was greater downregulation of ß1-, α1- and dopamine-1 receptors, more left ventricular involvement, and greater impairment of RV contractile reserve. RV GRK2 activity increased in parallel with a reduction in both adrenergic receptor expression and inotrope-stimulated cAMP levels (P<0.01). ß1-receptor downregulation also occurred in human PAH-RVH. Dobutamine was superior to dopamine as an RV inotrope, both ex vivo and in vivo. CONCLUSIONS: GRK2-mediated desensitization-downregulation of adrenergic and dopaminergic receptors impairs inotropic reserve in PAH-RVH. Acute inotropic support in RVH is best accomplished by dobutamine, reflecting its better coupling to adenylyl cyclase and the reliance of dopamine on dopamine-1-receptor signaling, which is impaired in RVH. Inhibiting Gßγ-GRK2 interactions has therapeutic benefit in RVH.

G protein-coupled receptor kinase-2 is a novel regulator of collagen synthesis in adult human cardiac fibroblasts.

Cardiac fibroblasts (CF) make up 60-70% of the total cell number in the heart and play a critical role in regulating normal myocardial function and in adverse remodeling following myocardial infarction and the transition to heart failure. Recent studies have shown that increased intracellular cAMP can inhibit CF transformation and collagen synthesis in adult rat CF; however, mechanisms by which cAMP production is regulated in CF have not been elucidated. We investigated the potential role of G protein-coupled receptor kinase-2 (GRK2) in modulating collagen synthesis by adult human CF isolated from normal and failing left ventricles. Baseline collagen synthesis was elevated in failing CF and was not inhibited by ß-agonist stimulation in contrast to normal controls. ß-adrenergic receptor (ß-AR) signaling was markedly uncoupled in the failing CF, and expression and activity of GRK2 were increased 3-fold. Overexpression of GRK2 in normal CF recapitulated a heart failure phenotype with minimal inhibition of collagen synthesis following ß-agonist stimulation. In contrast, knockdown of GRK2 expression in normal CF enhanced cAMP production and led to greater ß-agonist-mediated inhibition of basal and TGFß-stimulated collagen synthesis versus control. Inhibition of GRK2 activity in failing CF by expression of the GRK2 inhibitor, GRK2ct, or siRNA-mediated knockdown restored ß-agonist-stimulated inhibition of collagen synthesis and decreased collagen synthesis in response to TGFß stimulation. GRK2 appears to play a significant role in regulating collagen synthesis in adult human CF, and increased activity of this kinase may be an important mechanism of maladaptive ventricular remodeling as mediated by cardiac fibroblasts.

Supply and demographic characteristics of Ontario's ophthalmologists from 2010 to 2019: a population-based analysis.

BACKGROUND: With an aging population in Ontario, ophthalmologists provide most of their care to older adults, which has prominent human resource implications. In this study, we sought to investigate the supply and demographic characteristics of Ontario's ophthalmologists. METHODS: In this retrospective, population-based analysis, we evaluated cohort demographics, including sex and career stage, of Ontario's ophthalmologists from 2010 to 2019, which we reported using descriptive statistics. Similarly, we detailed ophthalmologist supply within different areas of care using descriptive statistics. RESULTS: Over the study period, a median of 464 ophthalmologists were practising in Ontario each year. The proportion of female ophthalmologists increased from 18.7% in 2010 to 24.1% in 2019. The proportion of late-career ophthalmologists (aged > 55 yr) significantly increased by 6.4% over the study period and constituted 45.3% of the workforce in 2019. Comprehensive cataract surgery was the most common area of care. Although the number of ophthalmologists per 100 000 people remained stable over the study period (3.27 ophthalmologists/100 000 people in 2019), the number of ophthalmologists per 100 000 people aged 65 years and older fell by 18.4% from 2010 to 2019. The greatest supply reduction was among moderate-volume comprehensive cataract surgeons (-20.2% overall and -35.4% relative to the population aged ≥ 65 yr). INTERPRETATION: Between 2010 and 2019, the overall number of ophthalmologists in Ontario remained stable; however, we observed declines in the number of ophthalmologists per 100 000 people aged 65 years and older for most areas of care. Nearly half of the ophthalmology workforce is now older than 55 years and female representation is increasing.

"Could You Work in My Team?": Exploring How Professional Clinical Role Expectations Influence Decision-Making of Assessors During Exit-Level Medical School OSCEs.

Decision-making in clinical assessment, such as exit-level medical school Objective Structured Clinical Examinations (OSCEs), is complex. This study utilized an empirical phenomenological qualitative approach with thematic analysis to explore OSCE assessors' perceptions of the concept of a "prototypical intern" expressed during focus group discussions. Topics discussed included the concept of a prototypical intern, qualities to be assessed, and approaches to clinical assessment decision-making. The thematic analysis was then applied to a theoretical framework (Cultural Historical Activity Theory-CHAT) that explored the complexity of making assessment decisions amidst potentially contradicting pressures from academic and clinical perspectives. Ten Australasian medical schools were involved with 15 experienced and five less experienced assessors participating. Thematic analysis of the data revealed four major themes in relation to how the prototypical intern concept influences clinical assessors' judgements: (a) Suitability of marking rubric based on assessor characteristics and expectations; (b) Competence as final year student vs. performance as a prototypical intern; (c) Safety, trustworthiness and reliability as constructs requiring assessment and (d) Contradictions in decision making process due to assessor differences. These themes mapped well within the interaction between two proposed activity systems in the CHAT model: academic and clinical. More clinically engaged and more experienced assessors tend to fall back on a heuristic, mental construct of a "prototypical intern," to calibrate judgements, particularly, in difficult situations. Further research is needed to explore whether consensus on desirable intern qualities and their inclusion into OSCE marksheets decreases the cognitive load and increases the validity of assessor decision making.

G alpha(q)-mediated activation of GRK2 by mechanical stretch in cardiac myocytes: the role of protein kinase C.

G protein-coupled receptor kinase-2 (GRK2) is a critical regulator of beta-adrenergic receptor (beta-AR) signaling and cardiac function. We studied the effects of mechanical stretch, a potent stimulus for cardiac myocyte hypertrophy, on GRK2 activity and beta-AR signaling. To eliminate neurohormonal influences, neonatal rat ventricular myocytes were subjected to cyclical equi-biaxial stretch. A hypertrophic response was confirmed by "fetal" gene up-regulation. GRK2 activity in cardiac myocytes was increased 4.2-fold at 48 h of stretch versus unstretched controls. Adenylyl cyclase activity was blunted in sarcolemmal membranes after stretch, demonstrating beta-AR desensitization. The hypertrophic response to mechanical stretch is mediated primarily through the G alpha(q)-coupled angiotensin II AT(1) receptor leading to activation of protein kinase C (PKC). PKC is known to phosphorylate GRK2 at the N-terminal serine 29 residue, leading to kinase activation. Overexpression of a mini-gene that inhibits receptor-G alpha(q) coupling blunted stretch-induced hypertrophy and GRK2 activation. Short hairpin RNA-mediated knockdown of PKC alpha also significantly attenuated stretch-induced GRK2 activation. Overexpression of a GRK2 mutant (S29A) in cardiac myocytes inhibited phosphorylation of GRK2 by PKC, abolished stretch-induced GRK2 activation, and restored adenylyl cyclase activity. Cardiac-specific activation of PKC alpha in transgenic mice led to impaired beta-agonist-stimulated ventricular function, blunted cyclase activity, and increased GRK2 phosphorylation and activity. Phosphorylation of GRK2 by PKC appears to be the primary mechanism of increased GRK2 activity and impaired beta-AR signaling after mechanical stretch. Cross-talk between hypertrophic signaling at the level of PKC and beta-AR signaling regulated by GRK2 may be an important mechanism in the transition from compensatory ventricular hypertrophy to heart failure.

Molecular and functional characterization of a novel cardiac-specific human tropomyosin isoform.

BACKGROUND: Tropomyosin (TM), an essential actin-binding protein, is central to the control of calcium-regulated striated muscle contraction. Although TPM1alpha (also called alpha-TM) is the predominant TM isoform in human hearts, the precise TM isoform composition remains unclear. METHODS AND RESULTS: In this study, we quantified for the first time the levels of striated muscle TM isoforms in human heart, including a novel isoform called TPM1kappa. By developing a TPM1kappa-specific antibody, we found that the TPM1kappa protein is expressed and incorporated into organized myofibrils in hearts and that its level is increased in human dilated cardiomyopathy and heart failure. To investigate the role of TPM1kappa in sarcomeric function, we generated transgenic mice overexpressing cardiac-specific TPM1kappa. Incorporation of increased levels of TPM1kappa protein in myofilaments leads to dilated cardiomyopathy. Physiological alterations include decreased fractional shortening, systolic and diastolic dysfunction, and decreased myofilament calcium sensitivity with no change in maximum developed tension. Additional biophysical studies demonstrate less structural stability and weaker actin-binding affinity of TPM1kappa compared with TPM1alpha. CONCLUSIONS: This functional analysis of TPM1kappa provides a possible mechanism for the consequences of the TM isoform switch observed in dilated cardiomyopathy and heart failure patients.

High-molecular-weight polyethylene glycol protects cardiac myocytes from hypoxia- and reoxygenation-induced cell death and preserves ventricular function.

Apoptosis plays a significant role in maladaptive remodeling and ventricular dysfunction following ischemia-reperfusion injury. There is a critical need for novel approaches to inhibit apoptotic cell death following reperfusion, as this loss of cardiac myocytes can progressively lead to heart failure. We investigated the ability and signaling mechanisms of a high-molecular-weight polyethylene glycol-based copolymer, PEG 15-20, to protect cardiac myocytes from hypoxia-reoxygenation (H-R)-induced cell death and its efficacy in preserving ventricular function following extended hypothermic ischemia and warm reperfusion as relevant to cardiac transplantation. Pretreatment of neonatal rat ventricular myocytes with a 5% PEG solution led to a threefold decline in apoptosis after H-R relative to untreated controls. There was a similar decline in caspase-3 activity in conjunction with inhibition of cytochrome c release from the inner mitochondrial membrane. Treatment with PEG also reduced reactive oxygen species production after H-R, and sarcolemmal lipid-raft architecture was preserved, consistent with membrane stabilization. Cell survival signaling was upregulated after H-R with PEG, as demonstrated by increased phosphorylation of Akt, GSK-3ß, and ERK1/2. There was also maintenance of cardiac myocyte ß-adrenergic signaling, which is critical for myocardial function. PEG 15-20 was very effective in preserving left ventricular function following prolonged hypothermic ischemia and warm reperfusion. PEG 15-20 has a potent protective antiapoptotic effect in cardiac myocytes exposed to H-R injury and may represent a novel therapeutic strategy to decrease myocardial cell death and ventricular dysfunction at the time of reperfusion during acute coronary syndrome or following prolonged donor heart preservation.

Deep-learning-based direct synthesis of low-energy virtual monoenergetic images with multi-energy CT.

Purpose: We developed a deep learning method to reduce noise and beam-hardening artifact in virtual monoenergetic image (VMI) at low x-ray energy levels. Approach: An encoder-decoder type convolutional neural network was implemented with customized inception modules and in-house-designed training loss (denoted as Incept-net), to directly estimate VMI from multi-energy CT images. Images of an abdomen-sized water phantom with varying insert materials were acquired from a research photon-counting-detector CT. The Incept-net was trained with image patches ( 64 × 64 pixels ) extracted from the phantom data, as well as synthesized, random-shaped numerical insert materials. The whole CT images ( 512 × 512 pixels ) with the remaining real insert materials that were unseen in network training were used for testing. Seven contrast-enhanced abdominal CT exams were used for preliminary evaluation of Incept-net generalizability over anatomical background. Mean absolute percentage error (MAPE) was used to evaluate CT number accuracy. Results: Compared to commercial VMI software, Incept-net largely suppressed beam-hardening artifact and reduced noise (53%) in phantom study. Incept-net presented comparable CT number accuracy at higher-density ( P -value [0.0625, 0.999]) and improved it at lower-density inserts ( P - value = 0.0313 ) with overall MAPE: Incept-net [2.9%, 4.6%]; commercial-VMI [6.7%, 10.9%]. In patient images, Incept-net suppressed beam-hardening artifact and reduced noise (up to 50%, P - value = 0.0156 ). Conclusion: In this preliminary study, Incept-net presented the potential to improve low-energy VMI quality.

Operational Recommendations for Scarce Resource Allocation in a Public Health Crisis.

The coronavirus disease 2019 pandemic may require rationing of various medical resources if demand exceeds supply. Theoretical frameworks for resource allocation have provided much needed ethical guidance, but hospitals still need to address objective practicalities and legal vetting to operationalize scarce resource allocation schemata. To develop operational scarce resource allocation processes for public health catastrophes, including the coronavirus disease 2019 pandemic, five health systems in Maryland formed a consortium-with diverse expertise and representation-representing more than half of all hospitals in the state. Our efforts built on a prior statewide community engagement process that determined the values and moral reference points of citizens and health-care professionals regarding the allocation of ventilators during a public health catastrophe. Through a partnership of health systems, we developed a scarce resource allocation framework informed by citizens' values and by general expert consensus. Allocation schema for mechanical ventilators, ICU resources, blood components, novel therapeutics, extracorporeal membrane oxygenation, and renal replacement therapies were developed. Creating operational algorithms for each resource posed unique challenges; each resource's varying nature and underlying data on benefit prevented any single algorithm from being universally applicable. The development of scarce resource allocation processes must be iterative, legally vetted, and tested. We offer our processes to assist other regions that may be faced with the challenge of rationing health-care resources during public health catastrophes.

Micro-anatomic alterations of the placenta in a non-human primate model of gestational protein-restriction.

OBJECTIVES: Maternal protein malnutrition is associated with impaired fetal growth, and lifetime consequences for the offspring. Our group has previously developed a model of protein-restriction in the non-human primate, which was associated with fetal growth restriction, stillbirth, decreased placental perfusion, and evidence of fetal hypoxia, suggesting perturbed vascular development. Our objective was to histologically characterize the micro-anatomic alterations associated with adverse pregnancy outcomes taking an approach that permits investigation of the 3D vascular structure and surrounding histology without the requirement for 3D vascular casting or relying on 2D stereology which both have methodological limitations. METHODS: Rhesus macaques were assigned in the pre-gestational period to a control diet that contained 26% protein, or study diet containing 13% protein (50% PR diet). Placental tissue was collected at delivery and processed using a clarification, immunohistochemistry, and confocal microscopy protocol published previously by our group. Three dimensional reconstructions and quantitative assessment of the vascular micro-anatomy was performed using analysis software (Imaris®) and statistical analysis accounted for maternal and fetal confounders. RESULTS: In unadjusted analysis, when comparing those pregnancies on a 50% PR diet (n = 4) with those on a control diet (n = 4), protein-restriction diet was associated with decreased maternal pre-pregnancy weight (difference of -1.975kg, 95% CI -3.267 to -0.6826). When controlling for maternal pre-pregnancy weight, fetal sex, and latency from tissue collection to imaging, a gestational protein-restriction diet was associated with decreases in total vascular length, total vascular surface area, total vascular volume, and vascular density. CONCLUSION: In this pilot study, a gestational protein-restriction diet altered the placental micro-vasculature with decreased vascular caliber and density, which may be related to the observed adverse pregnancy outcomes and perturbed placental perfusion previously demonstrated in this model.