Assuring the Groundwork for Success: Mentorship, Sponsorship, and Allyship for Practicing Anesthesiologists.

The challenges facing the health care industry in the post-coronavirus disease 2019 (COVID-19) pandemic world are numerous, jeopardizing wellness, and performance. Maintaining engagement and fulfillment of anesthesiologists in their work is now a critical issue in various practice settings: academic, private practice, and corporate medicine. In this article, we offer insights on how mentorship, sponsorship, and allyship are important in the advancement of the anesthesiology workforce including women and underrepresented minorities inclusive of race, gender, and disability. Mentorship, sponsorship, and allyship require a framework that intentionally addresses the programmatic structures needed to optimize the environment for increasing women, underrepresented minorities, and other diverse groups. These 3 distinct yet interrelated concepts are defined with a discussion on the value of implementation. In addition, the concept of "belonging" and its importance in enhancing the culture in anesthesiology is explored. We believe that part of the solution to wellness, recruitment and retention and improved job satisfaction of clinicians is having an environment where mentorship, sponsorship, and allyship are foundational.

The sequential natalizumab - alemtuzumab therapy in patients with relapsing forms of multiple sclerosis (SUPPRESS) trial - Part I: Rationale and objectives.

Background: Natalizumab is a recombinant humanized monoclonal antibody (mAb) against α4-integrin that is approved for relapsing forms of multiple sclerosis (MS). Natalizumab is associated with an increased risk of developing progressive multifocal leukoencephalopathy (PML), and with disease reactivation after cessation of treatment that is likely mediated by an accumulation of pro-inflammatory lymphocytes in the blood during therapy. Alemtuzumab is a mAb against CD52 that reduces the number of peripheral lymphocytes. Rationale: To determine if treatment with alemtuzumab after natalizumab reduces disease activity in patients with relapsing forms of MS. This review article will outline the rationale and objectives of the sequential natalizumab - alemtuzumab therapy in patients with relapsing forms of multiple sclerosis (SUPPRESS; ClinicalTrials.gov ID: NCT03135249) trial in greater detail than would be feasible in a manuscript that summarizes the study results. Methods: The SUPPRESS trial is single arm, open-label, multicenter, efficacy pilot study that aims to establish a disease-free state over a 24-months period in patients who received the natalizumab- alemtuzumab sequential therapy. Participants will be recruited from four different sites. The primary endpoint is the annualized relapse rate (ARR) from the time of cessation of natalizumab treatment. Key secondary endpoint is freedom of relapse at 12-months, the number of new/enlarging T2 lesions on magnetic resonance imaging (MRI), and the number of gadolinium (Gd)-enhancing lesions on MRI. An exploratory endpoint is the Expanded Disability Status Scale (EDSS), retinal nerve fiber layer (RNFL) thickness assessment by optic coherence tomography (OCT) and assessment of quality of life (QoL) measures by a pre-defined, self-administered testing battery. To evaluate immunological effects, blood leukocytes will be collected and immunophenotyped by multi-parameter flow cytometry. Conclusion: The SUPPRESS trial will provide clinical, imaging, and biological data to determine whether sequential natalizumab to alemtuzumab combination therapy establish a disease-free state in patients with relapsing forms of MS.

Regional anesthesia and the acute pain service: compliance and controversies.

PURPOSE OF REVIEW: The aims of this article are three-fold: first, to describe the necessary elements that result in accurate and compliant billing practice; second, to discuss billing in the context of new blocks and liposomal bupivacaine; and third, to gain a better understanding of compliance law. RECENT FINDINGS: Regional anesthesia techniques provide an appealing alternative to opioid medication for pain management. However, these techniques also increase the cost of care. As new peripheral and fascial plane blocks emerge, proper coding has become more complex. SUMMARY: Familiarity with documentation, billing, and compliance requirements can help maintain proper reimbursement rates, as well as limit potential downstream consequences. Most importantly this can help increase the viability and success of an acute pain service.

The disruptive physician and impact on the culture of safety.

PURPOSE OF REVIEW: The disruptive physician is a growing problem in medicine. All too often, physician behavior negatively impacts the delivery of quality patient care. The hostile environment that certain behaviors create makes it difficult for team members advocate for their patients. It is imperative that physician practices develop and an understanding of how to identify the disruptive physician to maintain patient safety. RECENT FINDINGS: Disruptive physicians can damage team morale by creating a psychologically unsafe working environment. Healthcare organizations must be committed to ensuring that all team members can function effectively in their work environments. The leaders of healthcare organizations must be acutely aware of what constitutes disruptive behavior and act proactively to eliminate such behaviors. Disruptive physicians should be made acutely aware that their behavior is deemed unacceptable and efforts at correcting such behavior are imperative. SUMMARY: The practice of medicine is multifaceted. It is imperative that the assurance of psychological safety is met to meet the standards of high quality and safe care for patients.

Tubal Ectopic Pregnancy with Undetectable Initial Serum ß-Human Chorionic Gonadotropin Level.

We present a case of a tubal ectopic pregnancy (EP) in a patient with an initially undetectable serum ß-human chorionic gonadotropin (ß-hCG) level. A 33-year-old woman in a same-sex relationship underwent timed donor intrauterine insemination. Her serum ß-hCG level was <5 mIU/mL 14 days after the intrauterine insemination. She reported menstrual bleeding 3 days after her negative pregnancy test and returned to the office 10 days later to begin a new treatment cycle. Her serum levels of estradiol, progesterone, and ß-hCG were 119 pg/mL, 6.1 ng/mL and 1157 mIU/mL, respectively. Transvaginal ultrasonography did not show an intrauterine pregnancy. Her ß-hCG level increased to 1420 mIU/mL the next day. She was diagnosed with a pregnancy of unknown location and treated with methotrexate. Her ß-hCG levels continued to increase despite 3 methotrexate doses, necessitating laparoscopy. The diagnostic laparoscopy demonstrated approximately 100 mL of hemoperitoneum in the posterior cul-de-sac with an intact right fallopian tube that was dilated at its distal end by the EP. A total right salpingectomy was performed. Her ß-hCG level was <5 mIU/mL 3 weeks later. The current case supports that although rare, an undetectable serum ß-hCG level does not completely rule out the diagnosis of an EP.

Asymptomatic progressive multifocal leukoencephalopathy: a case report and review of the literature.

BACKGROUND: We report the development of asymptomatic progressive multifocal leukoencephalopathy in a patient with multiple sclerosis on natalizumab therapy. Progressive multifocal leukoencephalopathy often presents with debilitating neurologic symptoms. Very few cases have documented a completely asymptomatic course of the disease. CASE PRESENTATION: A 26-year-old white woman with multiple sclerosis was treated with natalizumab. She was diagnosed as having progressive multifocal leukoencephalopathy based on characteristic magnetic resonance imaging lesions after 27 infusions of natalizumab. She had no neurologic deficits at the time of diagnosis and John Cunningham virus in cerebrospinal fluid was detected at 15 copies/ml. She was initially treated with mefloquine and mirtazapine and remained asymptomatic for 3 months. She later developed worsening magnetic resonance imaging lesions related to immune reconstitution inflammatory syndrome. At that time, she received intravenously administered immunoglobulin and high-dose intravenously administered methylprednisolone with radiologic improvement of the lesions. CONCLUSIONS: Our case report illustrates that early detection of asymptomatic progressive multifocal leukoencephalopathy and its subsequent treatment resulted in a benign clinical course. In consideration of the additional small number of cases of asymptomatic progressive multifocal leukoencephalopathy that have been reported, we conclude that routine magnetic resonance imaging surveillance is important for patients with multiple sclerosis who are at high risk for developing natalizumab-associated progressive multifocal leukoencephalopathy.

Meaningful Learning Moments on a Family Medicine Clerkship: When Students Are Patient Centered.

BACKGROUND AND OBJECTIVES: Reflection after patient encounters is an important aspect of clinical learning. After our medical school instituted a reflection paper assignment for all clerkships, we wanted to learn about the types of encounters that students found meaningful on a family medicine clerkship and how they impacted students' learning. METHODS: Family and Community Medicine Clerkship students completed a reflection paper after the clerkship, based on guidelines that were used for all clerkship reflection papers at our medical school. Two reviewers independently organized student responses into themes and then jointly prioritized common themes and negotiated any initial differences into other themes. RESULTS: A total of 272 reflection papers describing an actual learning moment in patient care were submitted during the study period of January 2011--December 2012. In describing actions performed, students most frequently wrote about aspects of patient-centered care such as listening to the patient, carefully assessing the patient's condition, or giving a detailed explanation to the patient. In describing effects of those actions, students wrote about what they learned about the patient-physician interaction, the trust that patients demonstrated in them, the approval they gained from their preceptors, and the benefits they saw from their actions. CONCLUSIONS: An important contribution of a family medicine clerkship is the opportunity for students to further their skills in patient-centered care and realize the outcomes of providing that type of care.

Online Faculty Development for Implementation and Use of Student Portfolios.

INTRODUCTION: Over the past decade, portfolios have gained popularity in medical education as tools to evaluate and provide feedback about learning and completion of professionally authentic tasks. Though faculty development has been noted to be key for successful portfolios, there are few available resources. As part of an interinstitutional collaborative project, we have developed online faculty development modules that provide pedagogical information about portfolios, practical advice, and resources from the available literature. METHODS: The materials associated with this publication include downloadable modules, which take approximately 45 minutes to complete and can be paused at any time, and sample questions to facilitate small-group discussion with faculty either in the planning stage of portfolios or as part of program evaluation of an institution's portfolios. RESULTS: A survey taken by faculty from four medical schools after completion of the modules showed that they were well received, with 41% of participants stating that they were very knowledgeable after undertaking the modules compared to 11% before undertaking the modules. Faculty reported increased interest in the topic and increased confidence in their ability to undertake planning for development of portfolios at their institution and considered using the modules as a mandatory curriculum for portfolio coaches at their institutions. DISCUSSION: We suggest that these modules be used for individual self-development, as part of faculty development sessions for portfolio coaches and mentors, or to provide faculty with background information about portfolios during the planning phase of portfolios at an institution.

Tissue-specific SMARCA4 binding at active and repressed regulatory elements during embryogenesis.

The SMARCA4 (also known as BRG1 in humans) chromatin remodeling factor is critical for establishing lineage-specific chromatin states during early mammalian development. However, the role of SMARCA4 in tissue-specific gene regulation during embryogenesis remains poorly defined. To investigate the genome-wide binding landscape of SMARCA4 in differentiating tissues, we engineered a Smarca4(FLAG) knock-in mouse line. Using ChIP-seq, we identified ∼51,000 SMARCA4-associated regions across six embryonic mouse tissues (forebrain, hindbrain, neural tube, heart, limb, and face) at mid-gestation (E11.5). The majority of these regions was distal from promoters and showed dynamic occupancy, with most distal SMARCA4 sites (73%) confined to a single or limited subset of tissues. To further characterize these regions, we profiled active and repressive histone marks in the same tissues and examined the intersection of informative chromatin states and SMARCA4 binding. This revealed distinct classes of distal SMARCA4-associated elements characterized by activating and repressive chromatin signatures that were associated with tissue-specific up- or down-regulation of gene expression and relevant active/repressed biological pathways. We further demonstrate the predicted active regulatory properties of SMARCA4-associated elements by retrospective analysis of tissue-specific enhancers and direct testing of SMARCA4-bound regions in transgenic mouse assays. Our results indicate a dual active/repressive function of SMARCA4 at distal regulatory sequences in vivo and support its role in tissue-specific gene regulation during embryonic development.

A genetic signature of spina bifida risk from pathway-informed comprehensive gene-variant analysis.

Despite compelling epidemiological evidence that folic acid supplements reduce the frequency of neural tube defects (NTDs) in newborns, common variant association studies with folate metabolism genes have failed to explain the majority of NTD risk. The contribution of rare alleles as well as genetic interactions within the folate pathway have not been extensively studied in the context of NTDs. Thus, we sequenced the exons in 31 folate-related genes in a 480-member NTD case-control population to identify the full spectrum of allelic variation and determine whether rare alleles or obvious genetic interactions within this pathway affect NTD risk. We constructed a pathway model, predetermined independent of the data, which grouped genes into coherent sets reflecting the distinct metabolic compartments in the folate/one-carbon pathway (purine synthesis, pyrimidine synthesis, and homocysteine recycling to methionine). By integrating multiple variants based on these groupings, we uncovered two provocative, complex genetic risk signatures. Interestingly, these signatures differed by race/ethnicity: a Hispanic risk profile pointed to alterations in purine biosynthesis, whereas that in non-Hispanic whites implicated homocysteine metabolism. In contrast, parallel analyses that focused on individual alleles, or individual genes, as the units by which to assign risk revealed no compelling associations. These results suggest that the ability to layer pathway relationships onto clinical variant data can be uniquely informative for identifying genetic risk as well as for generating mechanistic hypotheses. Furthermore, the identification of ethnic-specific risk signatures for spina bifida resonated with epidemiological data suggesting that the underlying pathogenesis may differ between Hispanic and non-Hispanic groups.

Large-scale discovery of enhancers from human heart tissue.

Development and function of the human heart depend on the dynamic control of tissue-specific gene expression by distant-acting transcriptional enhancers. To generate an accurate genome-wide map of human heart enhancers, we used an epigenomic enhancer discovery approach and identified ∼6,200 candidate enhancer sequences directly from fetal and adult human heart tissue. Consistent with their predicted function, these elements were markedly enriched near genes implicated in heart development, function and disease. To further validate their in vivo enhancer activity, we tested 65 of these human sequences in a transgenic mouse enhancer assay and observed that 43 (66%) drove reproducible reporter gene expression in the heart. These results support the discovery of a genome-wide set of noncoding sequences highly enriched in human heart enhancers that is likely to facilitate downstream studies of the role of enhancers in development and pathological conditions of the heart.

ChIP-Seq identification of weakly conserved heart enhancers.

Accurate control of tissue-specific gene expression plays a pivotal role in heart development, but few cardiac transcriptional enhancers have thus far been identified. Extreme noncoding-sequence conservation has successfully predicted enhancers that are active in many tissues but has failed to identify substantial numbers of heart-specific enhancers. Here, we used ChIP-Seq with the enhancer-associated protein p300 from mouse embryonic day 11.5 heart tissue to identify over 3,000 candidate heart enhancers genome wide. Compared to enhancers active in other tissues we studied at this time point, most candidate heart enhancers were less deeply conserved in vertebrate evolution. Nevertheless, transgenic mouse assays of 130 candidate regions revealed that most function reproducibly as enhancers active in the heart, irrespective of their degree of evolutionary constraint. These results provide evidence for a large population of poorly conserved heart enhancers and suggest that the evolutionary conservation of embryonic enhancers can vary depending on tissue type.

ChIP-seq accurately predicts tissue-specific activity of enhancers.

A major yet unresolved quest in decoding the human genome is the identification of the regulatory sequences that control the spatial and temporal expression of genes. Distant-acting transcriptional enhancers are particularly challenging to uncover because they are scattered among the vast non-coding portion of the genome. Evolutionary sequence constraint can facilitate the discovery of enhancers, but fails to predict when and where they are active in vivo. Here we present the results of chromatin immunoprecipitation with the enhancer-associated protein p300 followed by massively parallel sequencing, and map several thousand in vivo binding sites of p300 in mouse embryonic forebrain, midbrain and limb tissue. We tested 86 of these sequences in a transgenic mouse assay, which in nearly all cases demonstrated reproducible enhancer activity in the tissues that were predicted by p300 binding. Our results indicate that in vivo mapping of p300 binding is a highly accurate means for identifying enhancers and their associated activities, and suggest that such data sets will be useful to study the role of tissue-specific enhancers in human biology and disease on a genome-wide scale.

Mental health of college students and their non-college-attending peers: results from the National Epidemiologic Study on Alcohol and Related Conditions.

CONTEXT: Although young adulthood is often characterized by rapid intellectual and social development, college-aged individuals are also commonly exposed to circumstances that place them at risk for psychiatric disorders. OBJECTIVES: To assess the 12-month prevalence of psychiatric disorders, sociodemographic correlates, and rates of treatment among individuals attending college and their non-college-attending peers in the United States. DESIGN, SETTING, AND PARTICIPANTS: Face-to-face interviews were conducted in the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (N = 43,093). Analyses were done for the subsample of college-aged individuals, defined as those aged 19 to 25 years who were both attending (n = 2188) and not attending (n = 2904) college in the previous year. MAIN OUTCOME MEASURES: Sociodemographic correlates and prevalence of 12-month DSM-IV psychiatric disorders, substance use, and treatment seeking among college-attending individuals and their non-college-attending peers. RESULTS: Almost half of college-aged individuals had a psychiatric disorder in the past year. The overall rate of psychiatric disorders was not different between college-attending individuals and their non-college-attending peers. The unadjusted risk of alcohol use disorders was significantly greater for college students than for their non-college-attending peers (odds ratio = 1.25; 95% confidence interval, 1.04-1.50), although not after adjusting for background sociodemographic characteristics (adjusted odds ratio = 1.19; 95% confidence interval, 0.98-1.44). College students were significantly less likely (unadjusted and adjusted) to have a diagnosis of drug use disorder or nicotine dependence or to have used tobacco than their non-college-attending peers. Bipolar disorder was less common in individuals attending college. College students were significantly less likely to receive past-year treatment for alcohol or drug use disorders than their non-college-attending peers. CONCLUSIONS: Psychiatric disorders, particularly alcohol use disorders, are common in the college-aged population. Although treatment rates varied across disorders, overall fewer than 25% of individuals with a mental disorder sought treatment in the year prior to the survey. These findings underscore the importance of treatment and prevention interventions among college-aged individuals.

Neuropsychological testing in the screening for cochlear implant candidacy.

OBJECTIVE: To demonstrate the utility of neuropsychological assessment in the screening process for pediatric cochlear implant candidacy. STUDY DESIGN: Prospective and ongoing evaluation of children with profound bilateral hearing loss using age-specific neuropsychological test batteries. METHODS: Eighteen children who met audiological criteria for cochlear implantation were evaluated by two age-specific neuropsychological tests. The Vineland Adaptive Behavior Scales survey assesses several domains of behavioral functions (communication, daily living skills, socialization, and gross motor skills). The Mullen Scales of Early Learning assesses the child's visual perception, speech and language, and motor abilities. The Leiter International Performance Scale-Revised assesses intellectual ability. RESULTS: All patients underwent the Vineland Adaptive Behavior Scales survey. Overall scores were lower than normative means with a mean composite score in the 7th percentile. In addition, there was a strong inverse correlation between score and age of testing. Ten children were assessed using the Mullen Scales of Early Learning, and, again, there was a strong inverse correlation between score and age of testing. Intellectual ability was assessed in seven children using the Leiter International Performance Scale-Revised and was found to be lower than normative means with a mean score in the 13th percentile. CONCLUSIONS: Neuropsychological testing of profoundly deaf children provides a detailed and accurate assessment of the child's cognitive, behavioral, and motor functions. The profoundly deaf child does not develop at the same rate as normal children in cognitive and behavioral domains. Neuropsychological testing is a useful tool for screening for cochlear implant candidacy and has the potential to track changes before and after implantation.

An evidence-based review of the treatment of peritonsillar abscess.

OBJECTIVE: Peritonsillar abscess (PTA) is commonly seen but still controversial. We performed an evidence-based review to answer 3 questions: Are steroids beneficial? Which is the best technique for acute surgical management? When is tonsillectomy indicated? STUDY DESIGN: We performed a MEDLINE search of the published literature using appropriate search terms to identify pertinent articles, which were reviewed and graded according to the evidence quality. RESULTS: Forty-two articles were analyzed. There are no published studies on steroids in PTA. There were 5 level I clinical studies on surgical technique, which indicated that needle aspiration, incision and drainage, and quinsy tonsillectomy are all effective for initial management. The overall PTA recurrence rate is 10% to 15%. CONCLUSIONS: Overall, grade C evidence indicates that several methods of initial surgical drainage are equally effective, and the recurrence rate is low. The literature does not specifically address different treatments for children and adults.

Neuropsychological testing in the screening for cochlear implant candidacy.

OBJECTIVE: To demonstrate the utility of neuropsychological assessment in the screening process for pediatric cochlear implant candidacy. STUDY DESIGN: Prospective and ongoing evaluation of children with profound bilateral hearing loss using age-specific neuropsychological test batteries. METHODS: Eighteen children who met audiological criteria for cochlear implantation were evaluated by two age-specific neuropsychological tests. The Vineland Adaptive Behavior Scales survey assesses several domains of behavioral functions (communication, daily living skills, socialization, and gross motor skills). The Mullen Scales of Early Learning assess the child's visual perception, speech and language, and motor abilities. The Leiter International Performance Scale-Revised assesses intellectual ability. RESULTS: All patients underwent the Vineland Adaptive Behavior Scales survey. Overall scores were lower than normative means with a mean composite score in the 7th percentile. In addition, there was a strong inverse correlation between score and age of testing. Ten children were assessed using the Mullen Scales of Early Learning, and, again, there was a strong inverse correlation between score and age of testing. Intellectual ability was assessed in seven children using the Leiter International Performance Scale-Revised and was found to be lower than normative means with a mean score in the 13th percentile. CONCLUSIONS: Neuropsychological testing of profoundly deaf children provides a detailed and accurate assessment of the child's cognitive, behavioral, and motor functions. The profoundly deaf child does not develop at the same rate as normal children in cognitive and behavioral domains. Neuropsychological testing is a useful tool for screening for cochlear implant candidacy and has the potential to track changes before and after implantation.