Mapping structural and dynamic divergence across the MBOAT family.

Membrane-bound O-acyltransferases (MBOATs) are membrane-embedded enzymes that catalyze acyl chain transfer to a diverse group of substrates, including lipids, small molecules, and proteins. MBOATs share a conserved structural core, despite wide-ranging functional specificity across both prokaryotes and eukaryotes. The structural basis of catalytic specificity, regulation and interactions with the surrounding environment remain uncertain. Here, we combine comparative molecular dynamics (MD) simulations with bioinformatics to assess molecular and interactional divergence across the family. In simulations, MBOATs differentially distort the bilayer depending on their substrate type. Additionally, we identify lipid binding sites surrounding reactant gates in the surrounding membrane. Complementary bioinformatic analyses reveal a conserved role for re-entrant loop-2 in MBOAT fold stabilization and a key hydrogen bond bridging DGAT1 dimerization. Finally, we predict differences in MBOAT solvation and water gating properties. These data are pertinent to the design of MBOAT-specific inhibitors that encompass dynamic information within cellular mimetic environments.

Identifying Early-Phase Clinical Trial Participants at Risk for Experiencing Worse Clinical Outcomes.

PURPOSE: To identify early-phase clinical trial (EP-CT) participants at risk for experiencing worse clinical outcomes and describe receipt of supportive care services. METHODS: A retrospective review of the electronic health records of consecutive patients enrolled in EP-CTs from 2017 to 2019 examined baseline characteristics, clinical outcomes, and receipt of supportive care services. The validated Royal Marsden Hospital (RMH) prognosis score was calculated using data at the time of EP-CT enrollment (scores range from 0 to 3; scores ≥ 2 indicate poor prognosis). Differences in patient characteristics, clinical outcomes, and receipt of supportive care services were compared on the basis of RMH scores. RESULTS: Among 350 patients (median age = 63.2 years [range, 23.0-84.3 years], 57.1% female, 98.0% metastatic cancer), 31.7% had an RMH score indicating a poor prognosis. Those with poor prognosis RMH scores had worse overall survival (hazard ratio [HR], 2.00; P < .001), shorter time on trial (HR, 1.53; P < .001), and lower likelihood of completing the dose-limiting toxicity period (odds ratio, 0.42; P = .006) versus those with good prognosis scores. Patients with poor prognosis scores had greater risk of emergency room visits (HR, 1.66; P = .037) and hospitalizations (HR, 1.69; P = .016) while on trial, and earlier hospice enrollment (HR, 2.22; P = .006). Patients with poor prognosis scores were significantly more likely to receive palliative care consultation (46.8% v 27.6%; P < .001), but not other supportive care services. CONCLUSION: This study found that RMH prognosis score could identify patients at risk for decreased survival, shorter time on trial, and greater use of health care services. The findings underscore the need to develop supportive care interventions targeting EP-CT participants' distinct needs.

How to Reduce Stigma and Bias in Clinical Communication: a Narrative Review.

A growing body of literature demonstrates that healthcare providers use stigmatizing language when speaking and writing about patients. In April 2021, the 21st Century Cures Act compelled clinicians to make medical records open to patients. We believe that this is a unique moment to provide clinicians with guidance on how to avoid stigma and bias in our language as part of larger efforts to promote health equity. We performed an exhaustive scoping review of the gray and academic literature on stigmatizing medical language. We used thematic analysis and concept mapping to organize the findings into core principles for use in clinical practice. We compiled a list of terms to avoid and seven strategies to promote non-judgmental health record keeping: (1) use person-first language, (2) eliminate pejorative terms, (3) make communication inclusive, (4) avoid labels, (5) stop weaponizing quotes, (6) avoid blaming patients, and (7) abandon the practice of leading with social identifiers. While we offer guidance clinicians can use to promote equity through language on an individual level, health inequities are structural and demand simultaneous systems and policy change. By improving our language, we can disrupt the harmful narratives that allow health disparities to persist.

Implementation of a pilot novel objective peer comparison evaluation system in an emergency medicine residency program.

Objectives: Emergency medicine (EM) residents are currently evaluated via The Milestones, which have been shown to be imperfect and subjective. There is also a need for residents to achieve competency in patient safety and quality improvement processes, which can be accomplished through provision of peer comparison metrics. This pilot study aimed to evaluate the implementation of an objective peer comparison system for metrics that quantified aspects of quality and safety, efficiency and throughput, and utilization. Methods: This pilot study took place at an academic, tertiary care center with a 3-year residency and 14 residents per postgraduate year (PGY) class. Metrics were compared within each PGY class using Wilcoxon signed-rank and rank-order analyses. Results: Significant changes were seen in the majority of the metrics for all PGY classes. PGY3s accounted for the significant change in EKG and X-ray reads, while PGY1s and PGY2s accounted for the significant change in disposition to final note share. Physician evaluation to disposition decision was the only metric that did not reach significance in any class. Conclusions: These preliminary data suggest that providing objective metrics is possible. Peer comparison metrics could provide an effective objective addition to the milestone evaluation system currently in use.

Emergency Department-based Hepatitis A Vaccination Program in Response to an Outbreak.

INTRODUCTION: The Philadelphia Department of Public Health (PDPH) declared a public health emergency due to hepatitis A in August 2019. Our emergency department (ED) serves a population with many of the identified risk factors for hepatitis A transmission. This study examines the impact of an ED-based hepatitis A vaccination program, developed in partnership with the PDPH, on incidence of hepatitis A infection and hospital admission. METHODS: We conducted a retrospective review of all ED visits in the 12-week period centered around the implementation of the ED-based hepatitis A vaccination program. All adult patients presenting to the ED were offered vaccination, with vaccines supplied free of charge by the PDPH. We compared the incidence of diagnosis and of hospital admission for treatment of hepatitis A before and after implementation of the program. RESULTS: There were 10,033 total ED visits during the study period, with 5009 of them prior to the implementation of the vaccination program and 5024 after implementation. During the study period, 669 vaccines were administered. Before the vaccination program began, 73 patients were diagnosed with hepatitis A, of whom 67 were admitted. After implementation of the program, 38 patients were diagnosed with hepatitis A, of whom 31 were admitted. CONCLUSION: A partnership between an ED and the local public health department resulted in the vaccination of 669 patients in six weeks in the midst of an outbreak of a vaccine-preventable illness, with a corresponding drop in ED visits and hospital admission for acute hepatitis A.

The Impact of Due Process and Disruptions on Emergency Medicine Education in the United States.

INTRODUCTION: Academic Emergency Medicine (EM) departments are not immune to natural disasters, economic or political forces that disrupt a training program's operations and educational mission. Due process concerns are closely intertwined with the challenges that program disruption brings. Due process is a protection whereby an individual will not lose rights without access to a fair procedural process. Effects of natural disasters similarly create disruptions in the physical structure of training programs that at times have led to the displacement of faculty and trainees. Variation exists in the implementation of transitions amongst training sites across the country, and its impact on residency programs, faculty, residents and medical students. METHODS: We reviewed the available literature regarding due process in emergency medicine. We also reviewed recent examples of training programs that underwent disruptions. We used this data to create a set of best practices regarding the handling of disruptions and due process in academic EM. RESULTS: Despite recommendations from organized medicine, there is currently no standard to protect due process rights for faculty in emergency medicine training programs. Especially at times of disruption, the due process rights of the faculty become relevant, as the multiple parties involved in a transition work together to protect the best interests of the faculty, program, residents and students. Amongst training sites across the country, there exist variations in the scope and impact of due process on residency programs, faculty, residents and medical students. CONCLUSION: We report on the current climate of due process for training programs, individual faculty, residents and medical students that may be affected by disruptions in management. We outline recommendations that hospitals, training programs, institutions and academic societies can implement to enhance due process and ensure the educational mission of a residency program is given due consideration during times of transition.

Care of the Critically Ill Pregnant Patient and Perimortem Cesarean Delivery in the Emergency Department.

BACKGROUND: Maternal resuscitation in the emergency department requires planning and special consideration of the physiologic changes of pregnancy. Perimortem cesarean delivery (PMCD) is a rare but potentially life-saving procedure for both mother and fetus. Emergency physicians should be aware of the procedure's indications and steps because it needs to be performed rapidly for the best possible outcomes. OBJECTIVE: We sought to review the approach to the critically ill pregnant patient in light of new expert guidelines, including indications for PMCD and procedural techniques. DISCUSSION: The prevalence of maternal cardiac arrest and survival outcomes of PMCD in the emergency department setting are difficult to estimate. Advanced cardiovascular life support protocols should be followed in maternal arrest with special considerations made based on the physiologic changes of pregnancy. The latest recommendations for maternal resuscitation are reviewed, including advance planning, rapid determination of gestational age, emergent delivery, and postprocedure considerations for PMCD. CONCLUSIONS: Maternal resuscitation requires knowledge of physiologic changes and evidence-based recommendations. PMCD outcomes are best for both mother and fetus when the procedure is performed rapidly and efficiently in the appropriate setting. Emergency physicians should be familiar with this unique clinical scenario so they are adequately prepared to intervene in order to improve maternal and fetal morbidity and mortality.

The role of serial physical examinations in the management of angioedema involving the head and neck: A prospective observational study.

OBJECTIVE: To elucidate the progression of angioedema of the head and neck with routine management and to assess the utility of serial physical exams and fiberoptic laryngoscopy in its management. METHODS: This study was a prospective observational research. From 2013 to 2014, a prospective observational study was conducted at a tertiary referral center. Forty patient were approached, 7 refused, 33 (18-90 years old) were enrolled. Patients presented with angioedema involving the head and neck over a 12 month period were asked to participate in the study. Physical examination and fiberoptic laryngoscopy were performed at presentation and then repeated at least 1 h later. RESULTS: Thirty-three patients with head and neck angioedema from any cause were enrolled (mean age 58, range 23-89 years). The upper lip was the most commonly involved site (58%). On reevaluation, 82% of patients reported subjective improvement in symptoms. The association between subjective improvement and the physical exam, including fiberoptic laryngoscopy findings, was statistically significant (P < 0.001). CONCLUSION: In stable patients with angioedema of any head and neck subsite, self-reported symptoms are associated with clinical stability or improvement as assessed by physical signs and fiberoptic laryngoscopy. Patients' symptoms may be an appropriate surrogate to monitor clinical status without the need for routine serial physical examinations or fiberoptic laryngoscopy, though further study is needed.

Impact of an Opioid Prescribing Guideline in the Acute Care Setting.

BACKGROUND: Death from opioid abuse is a major public health issue. The death rate associated with opioid overdose nearly quadrupled from 1999 to 2008. Acute care settings are a major source of opioid prescriptions, often for minor conditions and chronic noncancer pain. OBJECTIVE: Our aim was to determine whether a voluntary opioid prescribing guideline reduces the proportion of patients prescribed opioids for minor and chronic conditions. METHODS: A retrospective chart review was performed on records of adult emergency department visits from January 2012 to July 2014 for dental, neck, back, or unspecified chronic pain, and the proportion of patients receiving opioid prescriptions at discharge was compared before and after the guideline. Attending emergency physicians were surveyed on their perceptions regarding the impact of the guideline on prescribing patterns, patient satisfaction, and physician-patient interactions. RESULTS: In our sample of 13,187 patient visits, there was a significant (p < 0.001) and sustained decrease in rates of opioid prescriptions for dental, neck, back, or unspecified chronic pain. The rate of opioid prescribing decreased from 52.7% before the guideline to 29.8% immediately after its introduction, and to 33.8% at an interval of 12 to 18 months later. The decrease in opioid prescriptions was observed in all of these diagnosis groups and in all age groups. All 31 eligible prescribing physicians completed a survey. The opioid prescribing guideline was supported by 100% of survey respondents. CONCLUSIONS: An opioid prescribing guideline significantly decreased the rates at which opioids were prescribed for minor and chronic complaints in an acute care setting.

Race/ethnicity and asthma management among adults presenting to the emergency department.

We investigated whether racial/ethnic disparities exist in asthma management among 1785 adults requiring emergency department (ED) treatment. In this multicentre study, non-Hispanic blacks with increased chronic asthma severity were only as likely (P > 0.05) as non-Hispanic whites or Hispanics to utilize controller medications or see asthma specialists before ED presentation and to be prescribed recommended inhaled corticosteroids at ED discharge. Improved ED education on evidence-based chronic disease management is needed to address continuing race/ethnicity-based asthma disparities.

Development of a process to disclose amyloid imaging results to cognitively normal older adult research participants.

INTRODUCTION: The objective of this study was to develop a process to maximize the safety and effectiveness of disclosing Positron Emission Tomography (PET) amyloid imaging results to cognitively normal older adults participating in Alzheimer's disease secondary prevention studies such as the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) Study. METHODS: Using a modified Delphi Method to develop consensus on best practices, we gathered and analyzed data over three rounds from experts in two relevant fields: informed consent for genetic testing or human amyloid imaging. RESULTS: Experts reached consensus on (1) text for a brochure that describes amyloid imaging to a person who is considering whether to undergo such imaging in the context of a clinical trial, and (2) a process for amyloid PET result disclosure within such trials. Recommendations included: During consent, potential participants should complete an educational session, where they receive verbal and written information covering what is known and unknown about amyloid imaging, including possible results and their meaning, implications of results for risk of future cognitive decline, and information about Alzheimer's and risk factors. Participants should be screened for anxiety and depression to determine suitability to receive amyloid imaging information. The person conducting the sessions should check comprehension and be skilled in communication and recognizing distress. Imaging should occur on a separate day from consent, and disclosure on a separate day from imaging. Disclosure should occur in person, with time for questions. At disclosure, investigators should assess mood and willingness to receive results, and provide a written results report. Telephone follow-up within a few days should assess the impact of disclosure, and periodic scheduled assessments of depression and anxiety, with additional monitoring and follow-up for participants showing distress, should be performed. CONCLUSIONS: We developed a document for use with potential study participants to describe the process of amyloid imaging and the implications of amyloid imaging results; and a disclosure process with attention to ongoing monitoring of both mood and safety to receive this information. This document and process will be used in the A4 Study and can be adapted for other research settings.

Gender differences in neurologic emergencies part I: a consensus summary and research agenda on cerebrovascular disease.

Cerebrovascular neurologic emergencies including ischemic and hemorrhagic stroke, subarachnoid hemorrhage (SAH), and migraine are leading causes of death and disability that are frequently diagnosed and treated in the emergency department (ED). Although sex and gender differences in neurologic emergencies are beginning to become clearer, there are many unanswered questions about how emergency physicians should incorporate sex and gender into their research initiatives, patient evaluations, and overall management plans for these conditions. After evaluating the existing gaps in the literature, a core group of ED researchers developed a draft of future research priorities. Participants in the 2014 Academic Emergency Medicine consensus conference neurologic emergencies working group then discussed and approved the recommended research agenda using a standardized nominal group technique. Recommendations for future research on the role of sex and gender in the diagnosis, treatment, and outcomes pertinent to ED providers are described for each of three diagnoses: stroke, SAH, and migraine. Recommended future research also includes investigation of the biologic and pathophysiologic differences between men and women with neurologic emergencies as they pertain to ED diagnoses and treatments.