Attributions and perpetrators of incivility in academic surgery.

Purpose: Although incivility has been described in other specialties, little is known about the attributes and perpetrators of it in academic surgery. The goal of this study was to identify attributes and commonly associated perpetrators of incivility experienced by trainees and faculty at academic surgery programs in the U.S. Methods: A web-based survey including the Workplace Incivility Scale (WIS) and questions regarding attributions and perpetrators of incivility was sent to trainees and faculty at academic institutions across the U.S. In addition to descriptive statistics, multivariable regression models were built to determine the impact of perpetrator type and number on overall incivility scores. Results: We received 367 of 2,661 (13.8%) responses. Top three reasons for incivility were surgery hierarchy (50.1%), respondent's gender (33.8%) and intergenerational differences (28.1%). Faculty (58.6%), patients (36.8%), and nursing staff (31.9%) were the most reported parties responsible for incivility. Female surgeons reported experiencing incivility more frequently from all three top responsible parties (i.e., faculty, patients, and nurses) when compared to other gender identities. Additionally, those who reported faculty (ß = 0.61, 95%CI 0.39-0.82) or nurses (ß = 0.23, 95%CI 0.009-0.45) as perpetrators of incivility reported an increase in overall incivility scores. Conclusions: Incivility in surgery is frequently attributed to surgery hierarchy, gender, and intergenerational differences. Surgical trainees and faculty reported that faculty, patients, and nurses were the most commonly identified as responsible for uncivil events in the surgical workforce. Exposure to a greater variety of perpetrators of incivility increases overall levels of incivility, emphasizing the importance of eliminating incivility from all sources. Supplementary Information: The online version contains supplementary material available at 10.1007/s44186-023-00129-1.

Structure-Reactivity Studies of 2-Sulfonylpyrimidines Allow Selective Protein Arylation.

Protein arylation has attracted much attention for developing new classes of bioconjugates with improved properties. Here, we have evaluated 2-sulfonylpyrimidines as covalent warheads for the mild, chemoselective, and metal free cysteine S-arylation. 2-Sulfonylpyrimidines react rapidly with cysteine, resulting in stable S-heteroarylated adducts at neutral pH. Fine tuning the heterocyclic core and exocyclic leaving group allowed predictable SNAr reactivity in vitro, covering >9 orders of magnitude. Finally, we achieved fast chemo- and regiospecific arylation of a mutant p53 protein and confirmed arylation sites by protein X-ray crystallography. Hence, we report the first example of a protein site specifically S-arylated with iodo-aromatic motifs. Overall, this study provides the most comprehensive structure-reactivity relationship to date on heteroaryl sulfones and highlights 2-sulfonylpyrimidine as a synthetically tractable and protein compatible covalent motif for targeting reactive cysteines, expanding the arsenal of tunable warheads for modern covalent ligand discovery.

International genetic counseling: What do genetic counselors actually do?

We conducted an exploratory survey of genetic counselors internationally to assess similarities and differences in reported practice activities. Between November 2018 and January 2020 we conducted a mass emailing to an estimated 5600 genetic counselors in different countries and regions. We obtained 189 useable responses representing 22 countries, which are included in an aggregate manner. Data from countries with 10 or more responses, comprising 82% of the total (N = 156), are the primary focus of this report: Australia (13), Canada (26), USA (59), UK (17), France (12), Japan (19) and India (10). Twenty activities were identified as common (≥74%) across these countries, encompassing most subcategories of genetic counseling activity. Activities with most frequent endorsement include: reviewing referrals and medical records and identifying genetic testing options as part of case preparation; taking family and medical histories; performing and sharing risk assessment; and educating clients about basic genetic information, test options, outcomes and implications, including management recommendations on the basis of the test results. Genetic counselors also consistently establish rapport, tailor the educational process, facilitate informed decision making and recognize factors that may impact the counseling interaction. The least endorsed activities were in the Medical History category. Notable differences between countries were observed in the endorsement of 33 activities, primarily in the Contracting and Establishing Rapport, Family History, Medical History, Assessing Patients Psychosocially and Providing Psychosocial Support categories. Generalizations about international practice patterns are limited by the low response rate. However, this study is, to our knowledge, the first to systematically compare the clinical practice and specific activities of genetic counselors working in different countries.

Survey of student mistreatment experienced during the core clinical clerkships.

BACKGROUND: The goal of this study was to learn more about the potential impact of medical student mistreatment on patient safety and care. METHODS: A web-based survey was sent to members of the class of 2021 and 2022 who have completed their core clerkships at a single academic institution. Descriptive statistics were performed to understand how prior and future mistreatment impacted communication among students and team members. RESULTS: We received 290 of 376 responses (77.1%). 26% of respondents indicated that past mistreatment negatively impacted their communication with other team members. 30% of respondents reported that fear of future mistreatment negatively impacted their communication with other team members. CONCLUSION: Mistreatment of medical students has many sources and occurs throughout the clinical curriculum. Past and fear of future student mistreatment can negatively impact intrateam communication and therefore negatively impact patient care, with the potential of causing poor patient outcomes.

Barriers to Colorectal Cancer Screening in US Immigrants: A Scoping Review.

INTRODUCTION: Timely colorectal cancer (CRC) screening has been shown to improve CRC-related morbidity and mortality rates. However, even with this preventative care tool, CRC screening rates remain below 70% among eligible United States (US) adults, with even lower rates among US immigrants. The aim of this scoping review is to describe the barriers to CRC screening faced by this unique and growing immigrant population and discuss possible interventions to improve screening. METHODS: Four electronic databases were systematically searched for all original research articles related to CRC screening in US immigrants published after 2010. Following a full-text review of articles for inclusion in the final analysis, data extraction was conducted while coding descriptive themes. Thematic analysis led to the organization of this data into five themes. RESULTS: Of the 4637 articles initially identified, 55 met inclusion criteria. Thematic analysis of the barriers to CRC screening identified five unique themes: access, knowledge, culture, trust, health perception, and beliefs. The most cited barriers were in access (financial burden and limited primary care access) and knowledge (CRC/screening knowledge). CONCLUSIONS: US immigrants face several barriers to the receipt of CRC screening. When designing interventions to increase screening uptake among immigrants, gaps in physician and screening education, access to care, and trust need to be addressed through culturally sensitive supports. These interventions should be tailored to the specific immigrant group, since a one-size-fits approach fails to consider the heterogeneity within this population.

Polygenic adaptation after a sudden change in environment.

Polygenic adaptation is thought to be ubiquitous, yet remains poorly understood. Here, we model this process analytically, in the plausible setting of a highly polygenic, quantitative trait that experiences a sudden shift in the fitness optimum. We show how the mean phenotype changes over time, depending on the effect sizes of loci that contribute to variance in the trait, and characterize the allele dynamics at these loci. Notably, we describe the two phases of the allele dynamics: The first is a rapid phase, in which directional selection introduces small frequency differences between alleles whose effects are aligned with or opposed to the shift, ultimately leading to small differences in their probability of fixation during a second, longer phase, governed by stabilizing selection. As we discuss, key results should hold in more general settings and have important implications for efforts to identify the genetic basis of adaptation in humans and other species.

Hereditary Cancer Risk Using a Genetic Chatbot Before Routine Care Visits.

OBJECTIVE: To examine user uptake and experience with a clinical chatbot that automates hereditary cancer risk triage by collecting personal and family cancer history in routine women's health care settings. METHODS: We conducted a multicenter, retrospective observational study of patients who used a web-based chatbot before routine care appointments to assess their risk for hereditary breast and ovarian cancer, Lynch syndrome, and adenomatous polyposis syndromes. Outcome measures included uptake and completion of the risk-assessment and educational section of the chatbot interaction and identification of hereditary cancer risk as evaluated against National Comprehensive Cancer Network criteria. RESULTS: Of the 95,166 patients invited, 61,070 (64.2%) engaged with the clinical chatbot. The vast majority completed the cancer risk assessment (89.4%), and most completed the genetic testing education section (71.4%), indicating high acceptability among those who opted to engage. The mean duration of use was 15.4 minutes (SD 2 hours, 56.2 minutes) when gaps of inactivity longer than 5 minutes were excluded. A personal history of cancer was reported by 19.1% (10,849/56,656) and a family history of cancer was reported by 66.7% (36,469/54,652) of patients who provided the relevant information. One in four patients (14,850/54,547) screened with the chatbot before routine care appointments met National Comprehensive Cancer Network criteria for genetic testing. Among those who were tested, 5.6% (73/1,313) had a disease-causing pathogenic variant. CONCLUSION: A chatbot digital health tool can help identify patients at high risk for hereditary cancer syndromes before routine care appointments. This scalable intervention can effectively provide cancer risk assessment, engage patients with educational information, and facilitate a path toward preventive genetic testing. FUNDING SOURCE: Implementation of the chatbot in clinics was funded by industry support from commercial genetic testing laboratories Ambry, Invitae, and Progenity.

Natural Language Processing and Assessment of Resident Feedback Quality.

OBJECTIVE: To validate the performance of a natural language processing (NLP) model in characterizing the quality of feedback provided to surgical trainees. DESIGN: Narrative surgical resident feedback transcripts were collected from a large academic institution and classified for quality by trained coders. 75% of classified transcripts were used to train a logistic regression NLP model and 25% were used for testing the model. The NLP model was trained by uploading classified transcripts and tested using unclassified transcripts. The model then classified those transcripts into dichotomized high- and low- quality ratings. Model performance was primarily assessed in terms of accuracy and secondary performance measures including sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC). SETTING: A surgical residency program based in a large academic medical center. PARTICIPANTS: All surgical residents who received feedback via the Society for Improving Medical Professional Learning smartphone application (SIMPL, Boston, MA) in August 2019. RESULTS: The model classified the quality (high vs. low) of 2,416 narrative feedback transcripts with an accuracy of 0.83 (95% confidence interval: 0.80, 0.86), sensitivity of 0.37 (0.33, 0.45), specificity of 0.97 (0.96, 0.98), and an area under the receiver operating characteristic curve of 0.86 (0.83, 0.87). CONCLUSIONS: The NLP model classified the quality of operative performance feedback with high accuracy and specificity. NLP offers residency programs the opportunity to efficiently measure feedback quality. This information can be used for feedback improvement efforts and ultimately, the education of surgical trainees.

Democratizing genomics: Leveraging software to make genetics an integral part of routine care.

Genetic testing can provide definitive molecular diagnoses and guide clinical management decisions from preconception through adulthood. Innovative solutions for scaling clinical genomics services are necessary if they are to transition from a niche specialty to a routine part of patient care. The expertise of specialists, like genetic counselors and medical geneticists, has traditionally been relied upon to facilitate testing and follow-up, and while ideal, this approach is limited in its ability to integrate genetics into primary care. As individuals, payors, and providers increasingly realize the value of genetics in mainstream medicine, several implementation challenges need to be overcome. These include electronic health record integration, patient and provider education, tools to stay abreast of guidelines, and simplification of the test ordering process. Currently, no single platform offers a holistic view of genetic testing that streamlines the entire process across specialties that begins with identifying at-risk patients in mainstream care settings, providing pretest education, facilitating consent and test ordering, and following up as a "genetic companion" for ongoing management. We describe our vision for using software that includes clinical-grade chatbots and decision support tools, with direct access to genetic counselors and pharmacists within a modular, integrated, end-to-end testing journey.

AVADA: toward automated pathogenic variant evidence retrieval directly from the full-text literature.

PURPOSE: Both monogenic pathogenic variant cataloging and clinical patient diagnosis start with variant-level evidence retrieval followed by expert evidence integration in search of diagnostic variants and genes. Here, we try to accelerate pathogenic variant evidence retrieval by an automatic approach. METHODS: Automatic VAriant evidence DAtabase (AVADA) is a novel machine learning tool that uses natural language processing to automatically identify pathogenic genetic variant evidence in full-text primary literature about monogenic disease and convert it to genomic coordinates. RESULTS: AVADA automatically retrieved almost 60% of likely disease-causing variants deposited in the Human Gene Mutation Database (HGMD), a 4.4-fold improvement over the current best open source automated variant extractor. AVADA contains over 60,000 likely disease-causing variants that are in HGMD but not in ClinVar. AVADA also highlights the challenges of automated variant mapping and pathogenicity curation. However, when combined with manual validation, on 245 diagnosed patients, AVADA provides valuable evidence for an additional 18 diagnostic variants, on top of ClinVar's 21, versus only 2 using the best current automated approach. CONCLUSION: AVADA advances automated retrieval of pathogenic monogenic variant evidence from full-text literature. Far from perfect, but much faster than PubMed/Google Scholar search, careful curation of AVADA-retrieved evidence can aid both database curation and patient diagnosis.

Victimization and traumatic stress: Pathways to depressive symptoms among low-income, African-American girls.

Socioeconomic disadvantage is associated with increased exposure to victimization and traumatic stress. The present study evaluates longitudinal pathways linking victimization and trauma to depressive symptoms in a socioeconomically disadvantaged sample of African-American adolescent girls seeking mental health services (N = 177, 12-16 years old at baseline). Girls completed four assessments over the course of three years (T1-T4). Depressive symptoms were assessed at T1-T3 using clinical interviews and questionnaires. At T4, lifetime history of victimization and traumatic stressors was evaluated with in-person interviews. Separate structural equation models tested longitudinal pathways from stressor frequency, severity, and duration to depressive symptoms. In all three models, higher levels of victimization and traumatic stressors were associated with significantly higher levels of depressive symptoms. More frequent stressors prior to T1 directly predicted depressive symptoms at T1 and indirectly predicted depressive symptoms at T2, which, in turn, predicted depressive symptoms at T3. A similar pattern emerged in the stressor severity and duration models. Findings support the idea that victimization and traumatic stressors are associated with higher levels of depressive symptoms and that, among treatment-seeking low-income adolescent girls, these effects occur through both direct and indirect paths. Implications of these findings are discussed in the context of the stress-generation and stress proliferation models of psychopathology.

Corrigendum: Minocycline as a re-purposed anti-Wolbachia macrofilaricide: superiority compared with doxycycline regimens in a murine infection model of human lymphatic filariasis.

This corrects the article DOI: 10.1038/srep23458.

Author Correction: Short-Course, High-Dose Rifampicin Achieves Wolbachia Depletion Predictive of Curative Outcomes in Preclinical Models of Lymphatic Filariasis and Onchocerciasis.

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.

Albendazole and antibiotics synergize to deliver short-course anti-Wolbachia curative treatments in preclinical models of filariasis.

Elimination of filariasis requires a macrofilaricide treatment that can be delivered within a 7-day period. Here we have identified a synergy between the anthelmintic albendazole (ABZ) and drugs depleting the filarial endosymbiont Wolbachia, a proven macrofilaricide target, which reduces treatment from several weeks to 7 days in preclinical models. ABZ had negligible effects on Wolbachia but synergized with minocycline or rifampicin (RIF) to deplete symbionts, block embryogenesis, and stop microfilariae production. Greater than 99% Wolbachia depletion following 7-day combination of RIF+ABZ also led to accelerated macrofilaricidal activity. Thus, we provide preclinical proof-of-concept of treatment shortening using antibiotic+ABZ combinations to deliver anti-Wolbachia sterilizing and macrofilaricidal effects. Our data are of immediate public health importance as RIF+ABZ are registered drugs and thus immediately implementable to deliver a 1-wk macrofilaricide. They also suggest that novel, more potent anti-Wolbachia drugs under development may be capable of delivering further treatment shortening, to days rather than weeks, if combined with benzimidazoles.

The Red Queen and King in finite populations.

In antagonistic symbioses, such as host-parasite interactions, one population's success is the other's loss. In mutualistic symbioses, such as division of labor, both parties can gain, but they might have different preferences over the possible mutualistic arrangements. The rates of evolution of the two populations in a symbiosis are important determinants of which population will be more successful: Faster evolution is thought to be favored in antagonistic symbioses (the "Red Queen effect"), but disfavored in certain mutualistic symbioses (the "Red King effect"). However, it remains unclear which biological parameters drive these effects. Here, we analyze the effects of the various determinants of evolutionary rate: generation time, mutation rate, population size, and the intensity of natural selection. Our main results hold for the case where mutation is infrequent. Slower evolution causes a long-term advantage in an important class of mutualistic interactions. Surprisingly, less intense selection is the strongest driver of this Red King effect, whereas relative mutation rates and generation times have little effect. In antagonistic interactions, faster evolution by any means is beneficial. Our results provide insight into the demographic evolution of symbionts.

Short-Course, High-Dose Rifampicin Achieves Wolbachia Depletion Predictive of Curative Outcomes in Preclinical Models of Lymphatic Filariasis and Onchocerciasis.

Lymphatic filariasis (LF) and onchocerciasis are priority neglected tropical diseases targeted for elimination. The only safe drug treatment with substantial curative activity against the filarial nematodes responsible for LF (Brugia malayi, Wuchereria bancrofti) or onchocerciasis (Onchocerca volvulus) is doxycycline. The target of doxycycline is the essential endosymbiont, Wolbachia. Four to six weeks doxycycline therapy achieves >90% depletion of Wolbachia in worm tissues leading to blockade of embryogenesis, adult sterility and premature death 18-24 months post-treatment. Long treatment length and contraindications in children and pregnancy are obstacles to implementing doxycycline as a public health strategy. Here we determine, via preclinical infection models of Brugia malayi or Onchocerca ochengi that elevated exposures of orally-administered rifampicin can lead to Wolbachia depletions from filariae more rapidly than those achieved by doxycycline. Dose escalation of rifampicin achieves >90% Wolbachia depletion in time periods of 7 days in B. malayi and 14 days in O. ochengi. Using pharmacokinetic-pharmacodynamic modelling and mouse-human bridging analysis, we conclude that clinically relevant dose elevations of rifampicin, which have recently been determined as safe in humans, could be administered as short courses to filariasis target populations with potential to reduce anti-Wolbachia curative therapy times to between one and two weeks.

Minocycline as a re-purposed anti-Wolbachia macrofilaricide: superiority compared with doxycycline regimens in a murine infection model of human lymphatic filariasis.

Lymphatic filariasis and onchocerciasis are parasitic helminth diseases, which cause severe morbidities such as elephantiasis, skin disease and blindness, presenting a major public health burden in endemic communities. The anti-Wolbachia consortium (A·WOL: http://www.a-wol.com/) has identified a number of registered antibiotics that target the endosymbiotic bacterium, Wolbachia, delivering macrofilaricidal activity. Here we use pharmacokinetics/pharmacodynamics (PK/PD) analysis to rationally develop an anti-Wolbachia chemotherapy by linking drug exposure to pharmacological effect. We compare the pharmacokinetics and anti-Wolbachia efficacy in a murine Brugia malayi model of minocycline versus doxycycline. Doxycycline exhibits superior PK in comparison to minocycline resulting in a 3-fold greater exposure in SCID mice. Monte-Carlo simulations confirmed that a bi-daily 25-40 mg/Kg regimen is bioequivalent to a clinically effective 100-200 mg/day dose for these tetracyclines. Pharmacodynamic studies showed that minocycline depletes Wolbachia more effectively than doxycycline (99.51% vs. 90.35%) after 28 day 25 mg/Kg bid regimens with a more potent block in microfilarial production. PK/PD analysis predicts that minocycline would be expected to be 1.7 fold more effective than doxycycline in man despite lower exposure in our infection models. Our findings warrant onward clinical investigations to examine the clinical efficacy of minocycline treatment regimens against lymphatic filariasis and onchocerciasis.

Prolonged Exposure Therapy With Veterans and Active Duty Personnel Diagnosed With PTSD and Traumatic Brain Injury.

The present study used archival clinical data to analyze the delivery and effectiveness of prolonged exposure (PE) and ancillary services for posttraumatic stress disorder (PTSD) among Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn veterans (N = 69) with histories of mild to severe traumatic brain injury (TBI). Data from standard clinical assessments of veterans and active duty personnel treated in both inpatient and outpatient programs at 2 Department of Veteran Affairs medical centers were examined. Symptoms were assessed with self-report measures of PTSD (PTSD Checklist) and depression (Beck Depression Inventory-II) before and throughout therapy. Mixed linear models were utilized to determine the slope of reported symptoms throughout treatment, and the effects associated with fixed factors such as site, treatment setting (residential vs. outpatient), and TBI severity were examined. Results demonstrated significant decreases in PTSD, B = -3.00, 95% CI [-3.22, -2.78]; t(210) = -13.5; p < .001, and in depressive symptoms, B = -1.46, 95% CI [-1.64, -1.28]; t(192) = -8.32; p < .001. The effects of PE treatment did not differ by clinical setting and participants with moderate to severe injuries reported more rapid gains than those with a history of mild TBI. The results provide evidence that PE may well be effective for veterans with PTSD and TBI.

Examining the factor structure of the Connor-Davidson Resilience Scale (CD-RISC) in a post-9/11 U.S. military veteran sample.

The present study examined the structural validity of the 25-item Connor-Davidson Resilience Scale (CD-RISC) in a large sample of U.S. veterans with military service since September 11, 2001. Participants (N = 1,981) completed the 25-item CD-RISC, a structured clinical interview and a self-report questionnaire assessing psychiatric symptoms. The study sample was randomly divided into two subsamples: an initial sample (Sample 1: n = 990) and a replication sample (Sample 2: n = 991). Findings derived from exploratory factor analysis (EFA) did not support the five-factor analytic structure as initially suggested in Connor and Davidson's instrument validation study. Although parallel analyses indicated a two-factor structural model, we tested one to six factor solutions for best model fit using confirmatory factor analysis. Results supported a two-factor model of resilience, composed of adaptability- (8 items) and self-efficacy-themed (6 items) items; however, only the adaptability-themed factor was found to be consistent with our view of resilience-a factor of protection against the development of psychopathology following trauma exposure. The adaptability-themed factor may be a useful measure of resilience for post-9/11 U.S. military veterans.

Inappropriate sexual behaviour and dementia: an exploration of staff experiences.

Research assessing the impact of inappropriate sexual behaviour (ISB) on staff working in dementia care is circumscribed, yet studies from comparable settings indicate that ISB appears uniquely challenging, particularly to personal and cultural values. This study explored staff experiences of ISB exhibited by older adults with a dementia. Fourteen staff working within an in-patient setting were interviewed. Participants' experiences of ISB appeared underpinned by complex social and psychological processes. Shock, embarrassment and incomprehension were prominent when ISB was initially encountered. Knowledge of dementia, familiarity with patients and social norms were important in contextualising ISB and staff often minimised its impact by construing a lack of capacity. Feelings about ISB appeared equivocal and findings suggest that the effect of ISB should be routinely considered in preparing staff who work within dementia care.