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.

Optimizing Upper-Tract Imaging for Non-Visible Haematuria.

INTRODUCTION: Non-visible haematuria (NVH) is associated with a small risk of upper-tract urothelial carcinoma (UTUC), though there is little consensus on its investigation, particularly with regard to upper-tract imaging. This study aimed to determine whether the presentation of UTUC can guide investigation of NVH in patients under 60 years old. METHODS: All patients investigated at our one-stop haematuria clinics under a cancer pathway were reviewed during a 5-year period, with all patients undergoing cystoscopy and upper-tract imaging. Retrospective analysis of all UTUC cases from our urological cancer multidisciplinary team meeting database over a 10-year period was also undertaken. RESULTS: 2,129 patients with a median age of 67 years underwent urgent investigation for haematuria between March 2015 and February 2020. 449 cases presented with NVH, of whom 124 (27.6%) were under 60. Out of 21 cases of UTUC, only 2 presented with NVH; both were over the age of 60 years. Factors that independently predicted diagnosis with urinary-tract malignancy were age ≥60 (OR 3.70, p < 0.001), visible haematuria (OR 2.50, p = 0.006), and suspicious cystoscopic findings (OR 58.06, p < 0.001). Review of all 119 UTUC cases over 10 years found 6 cases (5.0%) presenting with NVH, with one (0.8%) also presenting under 60 years. CONCLUSION: Diagnosis with UTUC is rare in patients presenting with NVH under the age of 60 years. Routine use of CTU in this low-risk group is best avoided, with ultrasonography constituting a safer first-line upper-tract imaging modality. Guidelines that risk-stratify NVH patients may be effective in reducing unnecessary investigations.

Bridging public and private health services to best meet the cardiometabolic needs of people with severe mental illness: a retrospective cohort study.

OBJECTIVE: Cardiovascular disease is the leading cause of premature mortality in people with severe mental illness (SMI). Despite this, there lacks consensus regarding the most appropriate platform to monitor and treat cardiometabolic risk factors in this cohort. The current study aims to evaluate the effectiveness of tailored cardiometabolic healthcare in a private, GP-led clinic for people with SMI. METHOD: A total of 63 adults with SMI were referred to a private GP-led cardiometabolic clinic from a neighbouring inner-city mental health service, where they received individualised cardiometabolic healthcare free-of-charge between 2014 and 2020. Paired t test was used to measure change in cardiometabolic data over the course of treatment. Chi-squared and Fisher's Exact tests were used to examine differences in demographic data and client engagement. RESULTS: Over a mean period of 9 months, there was a significant mean reduction of weight (2.1 kg), BMI (0.72 kg/m2) and waist circumference (6 cm). Engagement over a longer period was associated with stable accommodation and improved cardiometabolic outcomes. CONCLUSIONS: Targeted referral for individualised cardiometabolic interventions can lead to clinically significant improvement in cardiometabolic outcomes, providing a cause for therapeutic optimism when approaching physical health in people with SMI.

Sexual satisfaction and sexual distress after cancer: The role of body image disruption, self-compassion, sexual pain and relationship satisfaction.

OBJECTIVE: To identify variables that correlate with sexual satisfaction and sexual distress among adult cancer survivors, and how these differ, providing a basis from which approaches to intervention may be identified. This study examined four key variables: body image disruption, self-compassion, relationship satisfaction and sexual pain, previously all linked to sexual quality of life. METHODS: A cross-sectional survey was conducted online, with participants (n = 113) recruited via cancer charities, support groups and sexual counsellors' networks. A multivariate multiple regression analysis was conducted to analyse relationships among variables. RESULTS: In a regression adjusted for age, sex and time since diagnosis, higher sexual distress was significantly associated with higher body image disruption (ß = 0.23; p = 0.024), lower self-compassion (ß = -0.29; p = 0.009) and higher sexual pain (ß = 0.39; p < 0.001); but not relationship satisfaction (ß = -0.08; p = 0.434). Higher sexual satisfaction was significantly associated with higher relationship satisfaction (ß = 0.35; p = 0.002) and lower sexual pain (ß = -0.29; p = 0.005), but not body image disruption (ß = -0.19; p = 0.089), or self-compassion (ß = 0.06; p = 0.614). Sexual pain had a significantly stronger association with sexual distress than sexual satisfaction; F (1, 84) = 18.29, p < 0.001. CONCLUSIONS: Sexual distress and sexual satisfaction are associated with different psycho-social correlates even though both are used as indicators of sexual health. Research should seek to further understand the differences in these two critical markers of sexual health, with these differences likely to highlight the need to match interventions to the nature of the sexual difficulties experienced following cancer treatment.

Prevalence of and Preparedness to Address Inappropriate Sexual Behavior from Patients During Psychiatry Training: a Pilot Study.

OBJECTIVE: Mental health providers experience inappropriate sexual behavior from patients. It is unclear if training programs adequately prepare trainees to respond to such behaviors. Additionally, trainees may not seek support and guidance from supervisors after an incident. This is an exploratory study to document the prevalence of and assess the preparedness of trainees to deal with inappropriate sexual behavior. METHODS: A survey was administered to 58 psychiatry residents and 14 psychology interns at the NYU School of Medicine. A total of 22 questions were asked regarding participants' experiences with inappropriate sexual behavior, including prevalence of, and preparedness during, and support received after the behavior. RESULTS: Of those who completed the survey, 89% of respondents had experienced inappropriate sexual behavior. Seventy percent said they had no training in responding to inappropriate sexual behavior, and 95% wanted more training. A minority of respondents consistently sought support after these events, and of those who did, only 60% of trainees did so with a supervisor. CONCLUSION: Experiences involving inappropriate sexual behavior are prevalent among the mental health trainees surveyed, but most trainees did not feel that they received adequate training in preparation for or supervision after their experiences. Creating training or establishing protocols to respond to inappropriate sexual behavior may help trainees feel more capable and safer. Further studies are needed to understand inappropriate sexual behavior's impact on trainees and patient care, as well as to assess the efficacy of training and protocols developed to manage inappropriate sexual behavior.

A Content Analysis of the ACGME Specialty Milestones to Identify Performance Indicators Pertaining to the Development of Residents as Educators.

Construct: For curriculum development purposes, this study examined how the development of residents as educators is reflected in the Accreditation Council for Graduate Medical Education (ACGME) Milestones. Background: Residents teach patients, families, medical students, physicians, and other health professionals during and beyond their training. Despite this expectation, it is unclear how the development of residents as educators is reflected in the specialty-specific Milestones. Approach: We performed a textual content analysis of 25 specialty Milestone documents available as downloads from the ACGME website in December 2015. Syntactical units of interest included developmental progressions that describe the development of educators over the course of residency training and 16 key terms identified during the analysis. We then categorized the terms by associated Milestone level, ACGME core competency, and targeted learner(s). Results: We identified 10 developmental progressions and 546 instances of the 16 key terms that describe the development of physician educators. The frequency of terms among specialties was quite variable (5-46 terms per specialty, Mdn = 21). The majority of education-related terms appeared at advanced Milestone levels; there were 139 (26%) such instances in Level 4 and 296 (54%) in Level 5. Education-related terms were identified in all six ACGME core competencies, with greatest frequency in Patient Care (157, 29%). Other residents were the learners most frequently targeted by education-related Milestones (211, 40%). Conclusions: The current ACGME Milestones largely imply that resident teaching is a high-level or aspirational goal, achieved without a clear or consistently assessed developmental progression. These findings run counter to the theoretical basis that underlies the development of the Milestones. Wide variation among specialties indicates lack of consensus around the ideal skill set of the resident educator and limits the utility of these documents for curriculum development in this domain.

Brucellosis in Endangered Hector's Dolphins (Cephalorhynchus hectori).

Brucella spp infections of marine mammals are often asymptomatic but have been associated with reproductive losses and deaths. Zoonotic infections originating from marine isolates have also been described. Hector's dolphins (Cephalorhynchus hectori) are an endangered species with a declining population, and the role of infectious disease in population dynamics is not fully understood. In this study, 27 Hector's dolphins found dead around the New Zealand coastline between November 2006 and October 2010 were evaluated for lesions previously associated with cetacean brucellosis. Tissues were examined using histological, immunohistochemical, and molecular (polymerase chain reaction [PCR]) techniques. Seven of 27 dolphins (26%) had at least 1 tissue that was positive on PCR for Brucella spp. Lesions consistent with brucellosis were present in 10 of 27 (37%) dolphins, but in 8 of these dolphins Brucella infection could not be demonstrated in lesional tissues. Two dolphins (7%) were diagnosed with active brucellosis: 1 female with placentitis and metritis, and 1 stillborn male fetus. Brucella identified in these 2 dolphins had genetic similarity (99%) to Brucella pinnipedialis. The omp2a gene amplicon from the uterus of the female had 100% homology with ST27 genotype isolates from a human in New Zealand and a bottlenose dolphin of Pacific origin. The remaining 5 PCR-positive dolphins were assessed as having asymptomatic or latent infection. While most Brucella infections identified in this study appeared to be subclinical, the finding of 2 dolphins with reproductive disease due to Brucella infection suggests that this disease has the potential to affect reproductive success in this species.

Aß induces astrocytic glutamate release, extrasynaptic NMDA receptor activation, and synaptic loss.

Synaptic loss is the cardinal feature linking neuropathology to cognitive decline in Alzheimer's disease (AD). However, the mechanism of synaptic damage remains incompletely understood. Here, using FRET-based glutamate sensor imaging, we show that amyloid-ß peptide (Aß) engages α7 nicotinic acetylcholine receptors to induce release of astrocytic glutamate, which in turn activates extrasynaptic NMDA receptors (eNMDARs) on neurons. In hippocampal autapses, this eNMDAR activity is followed by reduction in evoked and miniature excitatory postsynaptic currents (mEPSCs). Decreased mEPSC frequency may reflect early synaptic injury because of concurrent eNMDAR-mediated NO production, tau phosphorylation, and caspase-3 activation, each of which is implicated in spine loss. In hippocampal slices, oligomeric Aß induces eNMDAR-mediated synaptic depression. In AD-transgenic mice compared with wild type, whole-cell recordings revealed excessive tonic eNMDAR activity accompanied by eNMDAR-sensitive loss of mEPSCs. Importantly, the improved NMDAR antagonist NitroMemantine, which selectively inhibits extrasynaptic over physiological synaptic NMDAR activity, protects synapses from Aß-induced damage both in vitro and in vivo.

ESCRT-mediated uptake and degradation of brain-targeted α-synuclein single chain antibody attenuates neuronal degeneration in vivo.

Parkinson's disease and dementia with Lewy bodies are neurodegenerative disorders characterized by accumulation of α-synuclein (α-syn). Recently, single-chain fragment variables (scFVs) have been developed against individual conformational species of α-syn. Unlike more traditional monoclonal antibodies, these scFVs will not activate or be endocytosed by Fc receptors. For this study, we investigated an scFV directed against oligomeric α-syn fused to the LDL receptor-binding domain from apolipoprotein B (apoB). The modified scFV showed enhanced brain penetration and was imported into neuronal cells through the endosomal sorting complex required for transport (ESCRT) pathway, leading to lysosomal degradation of α-syn aggregates. Further analysis showed that the scFV was effective at ameliorating neurodegenerative pathology and behavioral deficits observed in the mouse model of dementia with Lewy bodies/Parkinson's disease. Thus, the apoB modification had the effect of both increasing accumulation of the scFV in the brain and directing scFV/α-syn complexes for degradation through the ESCRT pathway, leading to improved therapeutic potential of immunotherapy.

Widespread microRNA dysregulation in multiple system atrophy - disease-related alteration in miR-96.

MicroRNA (miRNA) are short sequences of RNA that function as post-transcriptional regulators by binding to target mRNA transcripts resulting in translational repression. A number of recent studies have identified miRNA as being involved in neurodegenerative disorders including Alzheimer's disease, Parkinson's disease and Huntington's disease. However, the role of miRNA in multiple system atrophy (MSA), a progressive neurodegenerative disorder characterized by oligodendroglial accumulation of alpha-synuclein remains unexamined. In this context, this study examined miRNA profiles in MSA cases compared with controls and in transgenic (tg) models of MSA compared with non-tg mice. The results demonstrate a widespread dysregulation of miRNA in MSA cases, which is recapitulated in the murine models. The study employed a cross-disease, cross-species approach to identify miRNA that were either specifically dysregulated in MSA or were commonly dysregulated in neurodegenerative conditions such as Alzheimer's disease, dementia with Lewy bodies, progressive supranuclear palsy and corticobasal degeneration or the tg mouse model equivalents of these disorders. Using this approach we identified a number of miRNA that were commonly dysregulated between disorders and those that were disease-specific. Moreover, we identified miR-96 as being up-regulated in MSA. Consistent with the up-regulation of miR-96, mRNA and protein levels of members of the solute carrier protein family SLC1A1 and SLC6A6, miR-96 target genes, were down-regulated in MSA cases and a tg model of MSA. These results suggest that miR-96 dysregulation may play a role in MSA and its target genes may be involved in the pathogenesis of MSA.

Lentivirus mediated delivery of neurosin promotes clearance of wild-type α-synuclein and reduces the pathology in an α-synuclein model of LBD.

Neurosin is a predominant serine protease in the central nervous system (CNS) and has been shown to play a role in the clearance of α-synuclein (α-syn) which is centrally involved in the pathogenesis of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Although it has been previously shown that neurosin and α-syn colocalize and that neurosin degrades α-syn aggregates in vitro, it is not clear if neurosin is dysregulated in the brains of patients with PD/DLB and to what extent delivery of neurosin into the CNS might ameliorate the deficits associated with α-syn accumulation in vivo. We analyzed the levels of neurosin in the brains of patients with PD/DLB and in α-syn transgenic (tg) models. With increased accumulation of α-syn, we observed decreased neurosin expression. Lentiviral vector (LV) driven expression of neurosin in neuronal cell cultures reduced the accumulation of wild type but not A53T α-syn and prevented α-syn associated toxicity. Neuropathological analysis following delivery of LV-Neurosin to α-syn tg mice resulted in reduced accumulation of α-syn and reversal of neurodegenerative alterations in wild type but not A53T α-syn tg mice. Therefore, viral vector driven expression of neurosin may warrant further investigation as a potential therapeutic tool for DLB.

Utilization of marketing automation tools for delivery of a faculty development curriculum.

Background: Physician clinical educators play important roles in teaching, providing feedback, and evaluating trainees, but they often have variable preparation and competing demands on their time that make universal participation in workshops, seminars, or short courses designed to foster these skillsets inefficient or impossible. Methods: We designed and implemented a 52-week synchronous curriculum designed to address faculty opportunities to improve teaching skills, feedback for residents and medical students, and evaluation skills, which were delivered using marketing automation tools, including text messaging and email. We evaluated the programmatic impact and feasibility of using the implementation science framework. Results: Over a 104-week evaluation period, there were at least 10,499 total content impressions and 4558 unique recipients, indicating the significant reach of this program to approximately 120 faculty members. Faculty engagement with continuing education materials remained stable or increased over the 2-year evaluation period, indicating that programs like ours can have sustainable impacts. Resident evaluations of faculty across the six key domains also improved after the implementation of the program. Conclusions: Our experience with digital marketing tools reflects that they can be used to deliver impactful curricular content to faculty for continuing educational purposes and that faculty can use these resources in a sustainable way. However, because of the incomplete reach with any single communication, this type of content delivery is not appropriate for isolation as a material of critical importance. More research is needed to identify the best practices and additional education-related uses of this technology.

Pre-Operative Measures of Systemic Inflammation Predict Survival After Surgery for Primary Lung Cancer.

BACKGROUND: Measures of systemic inflammation (MSIs) have been developed and shown to help predict prognosis in patients with lung cancer. However, studies investigating the impact of MSIs on outcomes solely in cohorts of patients undergoing curative-intent resection of NSCLC are lacking. In the era of individualized therapies, targeting inflammatory pathways could represent a novel addition to the armamentarium of lung cancer treatment. METHODS: A multicentre retrospective review of patients who underwent primary lung cancer resection between 2012 and 2018 was undertaken. MSIs assessed were neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), systemic immune inflammation index (SII), advanced lung cancer inflammation index (ALI), prognostic nutritional index (PNI) and haemoglobin albumin lymphocyte platelet (HALP) score. Cox regression analysis was performed to assess the impact of MSIs on overall survival. RESULTS: A total of 5029 patients were included in the study. Overall 90-day mortality was 3.7% (n = 185). All MSIs were significantly associated with overall survival on univariable analysis. After multivariable Cox regression analyses, lower ALI (expressed as a continuous variable) (HR 1.000, 95% CI 1.000-1.000, P = .049) and ALI <366.43 (expressed as a dichotomous variable) (HR 1.362, 95% CI 1.137-1.631, P < .001) remained independently associated with reduced overall survival. CONCLUSIONS: MSIs have emerged in this study as potentially important factors associated with survival following lung resection for NSCLC with curative intent. In particular, ALI has emerged as independently associated with long-term outcomes. The role of MSIs in the clinical management of patients with primary lung cancer requires further investigation.

α-Synuclein in central nervous system and from erythrocytes, mammalian cells, and Escherichia coli exists predominantly as disordered monomer.

Since the discovery and isolation of α-synuclein (α-syn) from human brains, it has been widely accepted that it exists as an intrinsically disordered monomeric protein. Two recent studies suggested that α-syn produced in Escherichia coli or isolated from mammalian cells and red blood cells exists predominantly as a tetramer that is rich in α-helical structure (Bartels, T., Choi, J. G., and Selkoe, D. J. (2011) Nature 477, 107-110; Wang, W., Perovic, I., Chittuluru, J., Kaganovich, A., Nguyen, L. T. T., Liao, J., Auclair, J. R., Johnson, D., Landeru, A., Simorellis, A. K., Ju, S., Cookson, M. R., Asturias, F. J., Agar, J. N., Webb, B. N., Kang, C., Ringe, D., Petsko, G. A., Pochapsky, T. C., and Hoang, Q. Q. (2011) Proc. Natl. Acad. Sci. 108, 17797-17802). However, it remains unknown whether or not this putative tetramer is the main physiological form of α-syn in the brain. In this study, we investigated the oligomeric state of α-syn in mouse, rat, and human brains. To assess the conformational and oligomeric state of native α-syn in complex mixtures, we generated α-syn standards of known quaternary structure and conformational properties and compared the behavior of endogenously expressed α-syn to these standards using native and denaturing gel electrophoresis techniques, size-exclusion chromatography, and an oligomer-specific ELISA. Our findings demonstrate that both human and rodent α-syn expressed in the central nervous system exist predominantly as an unfolded monomer. Similar results were observed when human α-syn was expressed in mouse and rat brains as well as mammalian cell lines (HEK293, HeLa, and SH-SY5Y). Furthermore, we show that α-syn expressed in E. coli and purified under denaturing or nondenaturing conditions, whether as a free protein or as a fusion construct with GST, is monomeric and adopts a disordered conformation after GST removal. These results do not rule out the possibility that α-syn becomes structured upon interaction with other proteins and/or biological membranes.

Alpha-synuclein sequesters Dnmt1 from the nucleus: a novel mechanism for epigenetic alterations in Lewy body diseases.

DNA methylation is a major epigenetic modification that regulates gene expression. Dnmt1, the maintenance DNA methylation enzyme, is abundantly expressed in the adult brain and is mainly located in the nuclear compartment, where it has access to chromatin. Hypomethylation of CpG islands at intron 1 of the SNCA gene has recently been reported to result in overexpression of α-synuclein in Parkinson disease (PD) and related disorders. We therefore investigated the mechanisms underlying altered DNA methylation in PD and dementia with Lewy bodies (DLB). We present evidence of reduction of nuclear Dnmt1 levels in human postmortem brain samples from PD and DLB patients as well as in the brains of α-synuclein transgenic mice models. Furthermore, sequestration of Dnmt1 in the cytoplasm results in global DNA hypomethylation in human and mouse brains, involving CpG islands upstream of SNCA, SEPW1, and PRKAR2A genes. We report that association of Dnmt1 and α-synuclein might mediate aberrant subcellular localization of Dnmt1. Nuclear Dnmt1 levels were partially rescued by overexpression of Dnmt1 in neuronal cell cultures and in α-synuclein transgenic mice brains. Our results underscore a novel mechanism for epigenetic dysregulation in Lewy body diseases, which might underlie the decrease in DNA methylation reported for PD and DLB.

Ethanol alters opioid regulation of Ca(2+) influx through L-type Ca(2+) channels in PC12 cells.

BACKGROUND: Studies at the behavioral and synaptic level show that effects of ethanol on the central nervous system can involve the opioid signaling system. These interactions may alter the function of a common downstream target. In this study, we examined Ca(2+) channel function as a potential downstream target of interactions between ethanol and µ or κ opioid receptor signaling. METHODS: The studies were carried out in a model system, undifferentiated PC12 cells transfected with µ or κ opioid receptors. The PC12 cells express L-type Ca(2+) channels, which were activated by K(+) depolarization. Ca(2+) imaging was used to measure relative Ca(2+) flux during K(+) depolarization and the modulation of Ca(2+) flux by opioids and ethanol. RESULTS: Ethanol, µ receptor activation, and κ receptor activation all reduced the amplitude of the Ca(2+) signal produced by K(+) depolarization. Pretreatment with ethanol or combined treatment with ethanol and µ or κ receptor agonists caused a reduction in the amplitude of the Ca(2+) signal that was comparable to or smaller than that observed for the individual drugs alone, indicating an interaction by the drugs at a downstream target (or targets) that limited the modulation of Ca(2+) flux through L-type Ca(2+) channels. CONCLUSIONS: These studies provide evidence for a cellular mechanism that could play an important role in ethanol regulation of synaptic transmission and behavior through interactions with the opioid signaling.

Case for mandatory COVID-19 vaccinations for workers in health and aged care settings: a guide for leaders.

BACKGROUND: This brief paper provides an overview of the analysis in support of mandating COVID-19 vaccinations for all workers in health and aged care settings in Australia. Leaders of health and aged care organisations have a duty of care under work health and safety legislation to eliminate and/or control the risk of transmission of vaccine-preventable disease in their facilities, including COVID-19. METHODS: Key issues that should be considered by healthcare leaders when mandating that all health and aged care workers be vaccinated against COVID-19 were analysed by executives from a large Australian national health and aged care provider and discussed in this paper. RESULTS: This paper summarises the medical/scientific, ethical, legal, work health and safety, workers' compensation and industrial relations considerations when mandating COVID-19 vaccination for healthcare workers. CONCLUSION: Leaders of health and aged care organisations must provide a safe environment and workplace for all those who work for them, as well as for those who receive care or treatment at one of their facilities. It is hoped that this paper will assist leaders of healthcare organisations in making their own decisions during this time.

Clinical parameters of hypervirulent Klebsiella pneumoniae disease and ivermectin treatment in New Zealand sea lion (Phocarctos hookeri) pups.

Hypervirulent Klebsiella pneumoniae infection causes significant mortality of endangered New Zealand sea lion pups at Enderby Island, Auckland Islands. Gross necropsy and histopathology findings are well reported, but little is known about the clinical course of disease in affected pups. To determine factors feasible as clinical screening tools for hypervirulent K. pneumoniae in live pups, 150 pups over two field seasons (2016-18) were recruited shortly after birth for a prospective cohort study. A randomised controlled clinical treatment trial with the anthelmintic ivermectin was conducted concurrently and risk factor data and biological samples were collected approximately fortnightly. Treatment with ivermectin has been demonstrated to reduce the risk of hypervirulent K. pneumoniae mortality in pups, so effects on clinical parameters between the treated and control cohorts were also investigated. A broader sample of pups were monitored for clinical signs to investigate the course of disease in affected pups. Clinical signs, haematology and oral and rectal swabs to detect gastrointestinal carriage of hypervirulent K. pneumoniae were not useful for detection of disease prior to death. Of those pups that died due to hypervirulent K. pneumoniae, only 26.1% (18/69) had any clinical signs prior, likely a reflection of the peracute course of disease. On comparison of haematological parameters between ivermectin-treated and control pups, significantly lower total plasma protein and higher eosinophil counts were seen in control versus treated pups, however standard length as a surrogate for age was a more important influence on parameters overall than ivermectin treatment. This study also highlighted a cohort of pups with severe clinical signs suggestive of hypervirulent K. pneumoniae infection were lost to follow up at the end of the monitored season, which could be contributing to cryptic juvenile mortality.

Effect of resident complement on timeliness of stroke team activation in an academic emergency department.

OBJECTIVES: Investigations of the impact of residents on emergency department (ED) timeliness of care typically focus only on global ED flow metrics. We sought to describe the association between resident complement/supervisory ratios and timeliness of ED care of a specific time-sensitive condition, acute stroke. METHODS: We matched ED stroke patient arrivals at 1 academic stroke center against resident and attending staffing and constructed a Cox proportional hazards model of door-to-activation (DTA) time (ie, ED arrival ["door"] to stroke team activation). We considered multiple predictors, including calculated ratios of residents supervised by each attending physician. RESULTS: Among 462 stroke activation patients in 2014-2015, DTA ranged from 1 to 217 minutes, 72% within 15 minutes. The median number of emergency and off-service residents supervised per attending were 1.7 (interquartile range [IQR], 1.3-2.3) and 0.7 (IQR, 0-1), respectively. A 1-resident increase in off-service residents was associated with a 24% decrease (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.64-0.90) in the probability of stroke team activation at any given time. An independent 1-resident increase in the number of emergency residents was associated with a 13% increase (HR, 1.13; 95% CI, 1.01-1.25) in timely activation. CONCLUSION: Timeliness of care for acute stroke may be impacted by how academic EDs configure the complement and supervisory structures of residents. Higher supervisory demands imposed by increasing the proportion of rotating off-service residents may be associated with slower stroke recognition and DTA times, but this effect may be offset when more emergency residents are present.