Faculty Bibliography

Background By 2050 the worldwide incidence of hip fractures in men is projected to increase by 310%. It has been proposed that this increase will be due, in part, to the number of undiagnosed and untreated cases of osteoporosis in this population. Existing literature suggest that men may be under-screened, and screening recommendations for men lag behind those for women. The aim of this study was to identify the need for screening and appropriate follow up in this population by identifying the number of fractures that preceded screening, and assess whether these patients had appropriate treatment and follow up. Methods A retrospective chart review using the Computerized Patient Record System was performed on 1848 males aged 20-80, who had undergone DEXA scanning at the VA NY Harbor Healthcare System between 2011 and 2016. The primary endpoint for assessment was whether the DEXA scan was ordered in response to a fracture event. Among patients who suffered a fracture, a further assessment was performed to evaluate whether these patients were treated for osteoporosis and whether they suffered subsequent fractures. Time to follow up DEXA was also measured. Data was collected by three investigators using a standardized extraction algorithm. Results 1848 DEXA scans were performed on males from 2011 and 2016, including 485 individuals with a history of fracture. Average age at time of first fracture was 75. The 485 patients were assessed in two groups-those who had DEXA scans ordered in response to a fragility fracture (Group A: N=170) and those who had fractures following their first DEXA (Group B: N=315). In Group A, 30% received treatment for osteoporosis following their fracture and 40% of patients sustained another fracture (46% of the untreated patients and 23% of the treated patients). In Group B, 63% received treatment following the fracture. A further 25% sustained another fracture (13% of the treated patients, and 24% of the untreated patients). 47% of all patients had a follow up DEXA. Conclusion Given the high prevalence of fractures among males without a known history of osteoporosis, there is need for routine screening of this demographic of patients in order to prevent fractures. Fewer than half the patients had a follow up DEXA. Further, our data suggest that appropriate treatment can reduce the risk of subsequent fractures by 50%. We conclude that physicians should be educated on appropriate management of osteoporosis following fractures

Purpose: Evaluate the dose-ranging safety, tolerability, and pharmacokinetics (PK) of CBD in children with Dravet syndrome (DS). Method: Patients aged 4-10 years completed a 4-week baseline period and were randomised 4:1 to 1 of 3 CBD doses (5, 10, 20 mg/kg/day) or placebo as add-on therapy for 3 weeks. CBD (25 or 100 mg/mL oral solution) was administered BID starting at 2.5 mg/kg/day and increasing by 2.5 mg/kg QOD to randomised dose. On Days 1 and 22, PK exposures were expressed as AUC0-t. Dose proportionality was assessed on Day 22 by regression analysis. Adverse events (AEs) were recorded daily. Results: 34 patients were randomised to CBD 5 mg/kg/day (n = 10), 10 mg/kg/day (n = 8), 20 mg/kg/day (n = 9), or placebo (n = 7). Patients took a median 3 antiepileptic drugs (AEDs). On Day 22, exposures to CBD and major metabolites increased dose-proportionally; there was minimal change in clobazam levels, but concentrations of clobazam's metabolite, N-clobazam, increased independent of CBD dose, except in patients on stiripentol. There was no demonstrable effect on other AEDs (valproic acid, topiramate, stiripentol, levetiracetam). Most common AEs (CBD vs. placebo) were pyrexia (22% vs. 0%), somnolence (19% vs. 14%), decreased appetite (19% vs. 0%), and sedation (15% vs. 0%). Treatment-related serious AEs occurred in 2 patients on CBD and discontinuations due to AEs occurred in 2 patients on CBD. Increases in ALT or AST (levels >3 9 ULN) occurred in 6 patients on CBD, all on valproic acid; none had elevated bilirubin and all recovered. Conclusion: CBD was well tolerated and 20 mg/kg/day was chosen for further development. Exposure to CBD and its metabolites increased dose-proportionally. A PK interaction of CBD on N-clobazam was observed, likely mediated through CYP2C19 inhibition, except with stiripentol, presumably from prior saturated inhibition of CYP2C19 by stiripentol

INTRODUCTION/BACKGROUND:Epicardial catheter ablation is increasingly used to treat arrhythmias with an epicardial component. Nevertheless, percutaneous epicardial access remains associated with a significant risk of major complications. Developing a technology capable of confirming proper placement within the pericardial space could decrease complication rates. The purpose of this study was to examine differences in bioimpedance among the pericardial space, anterior mediastinum, and right ventricle. METHODS:An ovine model (n = 3) was used in this proof-of-concept study. A decapolar catheter was used to collect bipolar impedance readings; data were collected between each of five electrode pairs of varying distances. Data were collected from three test regions: the pericardial space, anterior mediastinum, and right ventricle. A control region in the inferior vena cava was used to normalize the data from the test regions. Analysis of variance was used to test for differences among regions. RESULTS:A total of 10 impedance values were collected in each animal between each of the five electrode pairs in the three test regions (n = 340) and the control region (n = 145). The average normalized impedance values were significantly different among the pericardial space (1.760 ± 0.370), anterior mediastinum (3.209 ± 0.227), and right ventricle (1.024 ± 0.207; P < 0.0001). In post hoc testing, the differences between each pair of regions were significant, as well (P < 0.001 for all). CONCLUSION/CONCLUSIONS:Impedance values are significantly different among these three anatomical compartments. Therefore, impedance can be potentially used as a means to guide percutaneous epicardial access.

Ceftolozane-tazobactam is a cephalosporin-β-lactamase inhibitor combination that exhibits potent in vitro activity against Pseudomonas aeruginosa, including strains that are resistant to other β-lactams. The emergence of ceftolozane-tazobactam resistance among clinical isolates of P. aeruginosa has rarely been described. Here we characterized ceftolozane-tazobactam-resistant P. aeruginosa strains recovered from a patient who was treated with this agent for 6 weeks for a recurrent wound infection. The results showed that the resistance was mediated by a single AmpC structural mutation.

INTRODUCTION: Remediating failing medical learners has traditionally been a craft activity responding to individual learner and remediator circumstances. Although there have been moves towards more systematic approaches to remediation (at least at the institutional level), these changes have tended to focus on due process and defensibility rather than on educational principles. As remediation practice evolves, there is a growing need for common theoretical and systems-based perspectives to guide this work. METHODS: This paper steps back from the practicalities of remediation practice to take a critical systems perspective on remediation in contemporary medical education. In doing so, the authors acknowledge the complex interactions between institutional, professional, and societal forces that are both facilitators of and barriers to effective remediation practices. RESULTS: The authors propose a model that situates remediation within the contexts of society as a whole, the medical profession, and medical education institutions. They also outline a number of recommendations to constructively align remediation principles and practices, support a continuum of remediation practices, destigmatize remediation, and develop institutional communities of practice in remediation. DISCUSSION: Medical educators must embrace a responsible and accountable systems-level approach to remediation if they are to meet their obligations to provide a safe and effective physician workforce.

CONTEXT: Ventricular assist devices (VADs) improve quality of life in advanced heart failure (HF) patients, but there are little data exploring psychological symptoms in this population. OBJECTIVE: This study examined the prevalence of psychiatric symptoms and disease over time in VAD patients. METHODS: This prospective multicenter cohort study enrolled patients immediately before or after VAD implant and followed them up to forty-eight weeks. Depression and anxiety were assessed with PROMIS SF8a questionnaires. The panic disorder, acute stress disorder (ASD) and post-traumatic stress disorder (PTSD) modules of the Structured Clinical Interview for the DSM were used. RESULTS: Eighty-seven patients were enrolled. Post-implant, depression and anxiety scores decreased significantly over time (p=0.03 and p<0.001 respectively). Two patients met criteria for panic disorder early after implantation but symptoms resolved over time. None met criteria for ASD or PTSD. CONCLUSIONS: Our study suggests VADs do not cause serious psychological harms and may have a positive impact on depression and anxiety. Furthermore, VADs did not induce PTSD, panic disorder or ASD in this cohort.

The NIDA funded Substance Abuse Education, Research and Training (SARET) Program addresses the compelling need for health professionals prepared to engage in substance use disorders (SUD) research. The goal of this interprofessional project, structured by an Executive Committee of co-investigators from the disciplines of medicine, nursing, social work and dentistry, is to increase the skills of students from each discipline for interprofessional research collaboration and early career-development opportunities in SUD research. The development of web-based modules, interprofessional seminars and a model mentorship program were designed as well, for dissemination and evaluation by other health professional schools. The educational format is 6 interactive web-based learning modules, providing an overview of core content on Substance Use Disorders (SUD), summer or year-long mentored research experiences with NIH-funded researchers and small interprofessional seminars and site visits. Assessment consists of self-reported annual student learning outcomes and external editorial and advisory board project and curricular materials review. These reviews encourages the updating of materials and provide flexibility for participating "champions" at other schools who use the modules. Quantitative and qualitative outcomes of student research activities and data on dissemination of modules support the fit between project content and interprofessional teaching modalities. The learning modules are available without charge to individuals, students, faculty or health professional programs from the project's website.

INTRODUCTION: Transitions to residency programs are designed to maximize quality and safety of patient care, as medical students become residents. However, best instructional or readiness assessment practices are not yet established. We sought to study the impact of a screen-based interactive curriculum designed to prepare interns to address common clinical coverage issues (WISE OnCall) on the clinical skills demonstrated in simulation and hypothesize that performance would improve after completing the module. METHODS: Senior medical students were recruited to participate in this single group prestudy/poststudy. Students responded to a call from a standardized nurse (SN) and assessed a standardized patient (SP) with low urine output, interacted with a 45-minute WISE OnCall module on the assessment and management of oliguria, and then evaluated a different SP with low urine output of a different underlying cause. Standardized patients assessed clinical skills with a 37-item, behaviorally anchored checklist measuring clinical skills (intraclass correlation coefficient [ICC], 0.55-0.81). Standardized nurses rated care quality and safety and collaboration and interprofessional communication using a 33-item literature-based, anchored checklist (ICC, 0.47-0.52). Standardized patient and SN ratings of the same student performance were correlated (r, 0.37-0.62; P < 0.01). Physicians assessed clinical reasoning quality based on the students' patient encounter note (ICC, 0.55-0.68), ratings that did not correlate with SP and SN ratings. We compared pre-post clinical skills performance and clinical reasoning. Fifty-two medical students (31%) completed this institutional review board approved study. RESULTS: Performance as measured by the SPs, SNs, and the postencounter note all showed improvement with mostly moderate to large effect sizes (range of Cohen's d, 0.30-1.88; P < 0.05) after completion of the online module. Unexpectedly, professionalism as rated by the SP was poorer after the module (Cohen's d, -0.93; P = 0.000). DISCUSSION: A brief computer-based educational intervention significantly improved graduating medical students' clinical skills needed to be ready for residency.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Malignancy is the most common cause of hypercalcaemia in the inpatient setting. Most cases are caused by tumour production of parathyroid hormone-related protein and osseous metastases. In less than 1% of cases, hypercalcaemia is driven by increased production of 1,25-dihydroxyvitamin D (1,25(OH)₂D), a mechanism most commonly seen in haematological malignancies. Here, we describe a woman with metastatic small cell cervical carcinoma who developed hypercalcaemia secondary to paraneoplastic overproduction of 1,25(OH)₂D, a finding that, to our knowledge, has not been previously associated with this cancer. We also review the current cases of solid tumours reported to have this mechanism of hypercalcaemia and the evidence behind multiple therapeutic approaches.