Search

Background: Because practice-based learning and improvement (PBLI) is a core competency for residents, the fundamentals of PBLI should be developed in medical school. Purpose: Evaluate the effects of a PBLI module for 1st-year students at Dartmouth Medical School in 2004-05. Methods: Design. Randomized two-group trial (early and late intervention). Intervention. One half of students received the standard curriculum-reviewing student-patient-preceptor reports with their small-group facilitator and student colleagues. The other half received the PBLI-DMEDS module-reviewing student-patient-preceptor reports and applying PBLI methods to history and physical exam skills. Analysis. The module was assessed on (a) core learning of PBLI (pre- and postmodule); (b) student self-assessed proficiency in PBLI (pre- and postmodule); (c) student, faculty, and course leaders' satisfaction; and (d) time costs. Results: Pretest PBLI knowledge scores were similar in both groups; intervention students scored significantly higher after the PBLI-DMEDS module. Satisfaction of students, faculty, and course leaders was mixed. The time cost required to implement the module was excessive. Conclusions: The intervention effectively taught the basics of PBLI but did not integrate well into the core curriculum. Our multifaceted evaluation approach allowed us to amplify aspects of the intervention that worked well and discard those that did not. [ABSTRACT FROM AUTHOR]

Objective: Decision aids (DAs) have been shown to facilitate shared decision making about cancer screening. However, little data exist on optimal strategies for dissemination. Our objective was to compare different decision aid distribution models.Methods: Eligible patients received video decision aids for prostate cancer (PSA) or colon cancer screening (CRC) through 4 distribution methods. Outcome measures included DA loans (N), % of eligible patients receiving DA, and patient and provider satisfaction.Results: Automatically mailing DAs to all age/gender appropriate patients led to near universal receipt by screening-eligible patients, but also led to ineligible patients receiving DAs. Three different elective (non-automatic) strategies led to low rates of receipt. Clinician satisfaction was higher when patients viewed the DA before the visit, and this model facilitated implementation of the screening choice. Regardless of timing or distribution method, patient satisfaction was high.Conclusions: An automatic DA distribution method is more effective than relying on individual initiative. Enabling patients to view the DA before the visit is preferred.Practice Implications: Systematically offering DAs to all eligible patients before their appointments is the ideal strategy, but may be challenging to implement. [ABSTRACT FROM AUTHOR]

Background: Opioid overdose deaths are of great concern to public health, with over one million lives lost since 1999. While many efforts have been made to mitigate these, Black communities continue to experience a greater burden of fatalities than their white counterparts. This study aims to explore why by working with Black community members in Indianapolis through semi-structured interviews., Methods: Semi-structured one-on-one in-depth interviews were conducted in spring and summer of 2023 with Black residents (N = 23) of zip codes 46202, 46205, 46208, and 46218 in Indianapolis. Ten interview questions were used to facilitate conversations about opioid overdoses, recovery, fatality prevention tools such as calling 911 and naloxone, law enforcement, and racism. Data were analyzed using grounded theory and thematic analysis., Results: Interviews revealed access barriers and intervention opportunities. Racism was present in both. Mental access barriers such as stigma, fear, and mistrust contributed to practical barriers such as knowledge of how to administer naloxone. Racism exacerbated mental barriers by adding the risk of race-based mistreatment to consequences related to association with substance use. Participants discussed the double stigma of substance use and being Black, fear of being searched in law enforcement encounters and what would happen if law enforcement found naloxone on them, and mistrust of law enforcement and institutions that provide medical intervention. Participants had favorable views of interventions that incorporated mutual aid and discussed ideas for future interventions that included this framework., Conclusions: Racism exacerbates Blacks' mental access barriers (i.e., help-seeking barriers), which, in turn, contribute to practical barriers, such as calling 911 and administering naloxone. Information and resources coming from people within marginalized communities tend to be trusted. Leveraging inter-community relationships may increase engagement in opioid overdose fatality prevention. Interventions and resources directed toward addressing opioid overdose fatalities in Black communities should use mutual aid frameworks to increase the utilization of the tools they provide., (© 2023. The Author(s).)

Background: The triggering receptor expressed on myeloid cell 2 (TREM2) is a major regulator of neuroinflammatory processes in neurodegeneration. To date, the p.H157Y variant of TREM2 has been reported only in patients with Alzheimer's disease. Here, we report three patients with frontotemporal dementia (FTD) from three unrelated families with heterozygous p.H157Y variant of TREM2 : two patients from Colombian families (study 1) and a third Mexican origin case from the USA (study 2)., Methods: To determine if the p.H157Y variant might be associated with a specific FTD presentation, we compared in each study the cases with age-matched, sex-matched and education-matched groups-a healthy control group (HC) and a group with FTD with neither TREM2 mutations nor family antecedents (Ng-FTD and Ng-FTD-MND)., Results: The two Colombian cases presented with early behavioural changes, greater impairments in general cognition and executive function compared with both HC and Ng-FTD groups. These patients also exhibited brain atrophy in areas characteristic of FTD. Furthermore, TREM2 cases showed increased atrophy compared with Ng-FTD in frontal, temporal, parietal, precuneus, basal ganglia, parahippocampal/hippocampal and cerebellar regions. The Mexican case presented with FTD and motor neuron disease (MND), showing grey matter reduction in basal ganglia and thalamus, and extensive TDP-43 type B pathology., Conclusion: In all TREM2 cases, multiple atrophy peaks overlapped with the maximum peaks of TREM2 gene expression in crucial brain regions including frontal, temporal, thalamic and basal ganglia areas. These results provide the first report of an FTD presentation potentially associated with the p.H157Y variant with exacerbated neurocognitive impairments., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

A hallmark of chronic hepatitis B (CHB) virus infection is the presence of high circulating levels of non-infectious small lipid HBV surface antigen (HBsAg) vesicles. Although rare, sustained HBsAg loss is the idealized endpoint of any CHB therapy. A small molecule, RG7834, has been previously reported to inhibit HBsAg expression by targeting terminal nucleotidyltransferase proteins 4A and 4B (TENT4A and TENT4B). In this study, we describe a genome-wide CRISPR screen to identify other potential host factors required for HBsAg expression and to gain further insights into the mechanism of RG7834. We report more than 60 genes involved in regulating HBsAg and identify additional factors involved in RG7834 activity, including a zinc finger CCHC-type containing 14 (ZCCHC14) protein. We show that ZCCHC14, together with TENT4A/B, stabilizes HBsAg expression through HBV RNA tailing, providing a potential new therapeutic target to achieve functional cure in CHB patients., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction. We aimed to conduct a multinational cross-sectional online survey of medical students' attitudes toward, knowledge of, and experience with shared decision making (SDM). Methods. We conducted the survey from September 2016 until May 2017 using the following: 1) a convenience sample of students from four medical schools each in Canada, the United States, and the Netherlands ( n = 12), and 2) all medical schools in the United Kingdom through the British Medical School Council ( n = 32). We also distributed the survey through social media. Results. A total of 765 students read the information sheet and 619 completed the survey. Average age was 24, 69% were female. Mean SDM knowledge score was 83.6% (range = 18.8% to 100%; 95% confidence interval [CI] = 82.8% to 84.5%). US students had the highest knowledge scores (86.2%, 95% CI = 84.8% to 87.6%). The mean risk communication score was 57.4% (range = 0% to 100%; 95% CI = 57.4% to 60.1%). Knowledge did not vary with age, race, gender, school, or school year. Attitudes were positive, except 46% believed SDM could only be done with higher educated patients, and 80.9% disagreed that physician payment should be linked to SDM performance (increased with years in training, P < 0.05). Attitudes did not vary due to any tested variable. Students indicated they were more likely than experienced clinicians to practice SDM (72.1% v. 48.8%). A total of 74.7% reported prior SDM training and 82.8% were interested in learning more about SDM. Discussion. SDM knowledge is high among medical students in all four countries. Risk communication is less well understood. Attitudes indicate that further research is needed to understand how medical schools deliver and integrate SDM training into existing curricula., (© The Author(s) 2019.)

Bile acids are critical metabolites in the gastrointestinal tract and contribute to maintaining intestinal immune homeostasis through cross-talk with the gut microbiota. The conversion of bile acids by the gut microbiome is now recognized as a factor affecting both host metabolism and immune responses, but its physiological roles remain unclear. We conducted a screen for microbiome metabolites that would function as inflammasome activators and herein report the identification of 12-oxo-lithocholic acid (BAA485), a potential microbiome-derived bile acid metabolite. We demonstrate that the more potent analogue 11-oxo-12 S -hydroxylithocholic acid methyl ester (BAA473) can induce secretion of interleukin-18 (IL-18) through activation of the inflammasome in both myeloid and intestinal epithelial cells. Using a genome-wide CRISPR screen with compound induced pyroptosis in THP-1 cells, we identified that inflammasome activation by BAA473 is pyrin-dependent ( MEFV ). To our knowledge, the bile acid analogues BAA485 and BAA473 are the first small molecule activators of the pyrin inflammasome. We surmise that pyrin inflammasome activation through microbiota-modified bile acid metabolites such as BAA473 and BAA485 plays a role in gut microbiota regulated intestinal immune response. The discovery of these two bioactive compounds may help to further unveil the importance of pyrin in gut homeostasis and autoimmune diseases., (© 2019 Alimov et al.)

Introduction: Shared decision making (SDM) is a goal of modern medicine; however, it is not currently embedded in routine care. Barriers include clinicians’ attitudes, lack of knowledge and training and time constraints. Our goal is to support the development and delivery of a robust SDM curriculum in medical education. Our objective is to assess undergraduate medical students’ knowledge of and attitudes towards SDM in four countries., Methods and Analysis: The first phase of the study involves a web-based cross-sectional survey of undergraduate medical students from all years in selected schools across the United States (US), Canada and undergraduate and graduate students in the Netherlands. In the United Kingdom (UK), the survey will be circulated to all medical schools through the UK Medical School Council. We will sample students equally in all years of training and assess attitudes towards SDM, knowledge of SDM and participation in related training. Medical students of ages 18 years and older in the four countries will be eligible. The second phase of the study will involve semistructured interviews with a subset of students from phase 1 and a convenience sample of medical school curriculum experts or stakeholders. Data will be analysed using multivariable analysis in phase 1 and thematic content analysis in phase 2. Method, data source and investigator triangulation will be performed. Online survey data will be reported according to the Checklist for Reporting the Results of Internet E-Surveys. We will use the COnsolidated criteria for REporting Qualitative research for all qualitative data., Ethics and Dissemination: The study has been approved for dissemination in the US, the Netherlands, Canada and the UK. The study is voluntary with an informed consent process. The results will be published in a peer-reviewed journal and will help inform the inclusion of SDM-specific curriculum in medical education worldwide., Competing Interests: Competing interests: Financial: M-AD is a consultant to Access Community Health Network, Chicago. GE has been a consultant to: (1) Emmi Solutions LLC who develop patient knowledge tools; (2) National Quality Forum on certification of patient knowledge tools; (3) Washington State Health Department on certification of patient knowledge tools; (4) PatientWisdom LLC, (5) SciMentum, Amsterdam, and (6) Access Community Health Network, Chicago. GE has edited / published books that provide royalties on sales by the publishers: the books have been on Shared Decision Making (Oxford University Press) and Groups (Radcliffe Press). Non-Financial: Many authors are authors of SDM and communication training programs in medical schools. However, they get no financial benefits from it. GE initiated and leads the Option Grid TM patient decision aids Collaborative, which produces and publishes patient knowledge tools in the form of comparison tables (http://optiongrid.org/), and has part ownership of the registered trademark. GE owns copyright in CollaboRATE, IntegRATE, and Observer OPTION measures of shared decision making and care integration. These measures are freely available for use. PJB owns copyright in CollaboRATE., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Macroautophagy is a key stress-response pathway that can suppress or promote tumorigenesis depending on the cellular context. Notably, Kirsten rat sarcoma (KRAS)-driven tumors have been reported to rely on macroautophagy for growth and survival, suggesting a potential therapeutic approach of using autophagy inhibitors based on genetic stratification. In this study, we evaluated whether KRAS mutation status can predict the efficacy to macroautophagy inhibition. By profiling 47 cell lines with pharmacological and genetic loss-of-function tools, we were unable to confirm that KRAS-driven tumor lines require macroautophagy for growth. Deletion of autophagy-related 7 (ATG7) by genome editing completely blocked macroautophagy in several tumor lines with oncogenic mutations in KRAS but did not inhibit cell proliferation in vitro or tumorigenesis in vivo. Furthermore, ATG7 knockout did not sensitize cells to irradiation or to several anticancer agents tested. Interestingly, ATG7-deficient and -proficient cells were equally sensitive to the antiproliferative effect of chloroquine, a lysosomotropic agent often used as a pharmacological tool to evaluate the response to macroautophagy inhibition. Moreover, both cell types manifested synergistic growth inhibition when treated with chloroquine plus the tyrosine kinase inhibitors erlotinib or sunitinib, suggesting that the antiproliferative effects of chloroquine are independent of its suppressive actions on autophagy.

Background: Avian influenza A/H5N1 has threatened human health for nearly 2 decades. Avian influenza A vaccine without adjuvant is poorly immunogenic. A flexible rapid tactic for mass vaccination will be needed if a pandemic occurs., Methods: A multicenter, randomized, blinded phase 1 clinical trial evaluated safety and antibody responses after point-of-use mixing of influenza A/Indonesia/05/2005 (H5N1) vaccine with MF59 adjuvant. Field-site pharmacies mixed 3.75, 7.5, or 15 mcg of antigen with or without MF59 adjuvant just prior to intramuscular administration on days 0 and 21 of healthy adults aged 18-49 years., Results: Two hundred and seventy subjects were enrolled. After vaccination, titers of hemagglutination inhibition antibody ≥1:40 were achieved in 80% of subjects receiving 3.75 mcg + MF59 vs only 14% receiving 15 mcg without adjuvant (P < .0001). Peak hemagglutination inhibition antibody geometric mean titers for vaccine + MF59 were ∼65 regardless of antigen dose, and neutralizing titers were 2- to 3-fold higher. Vaccine + MF59 produced cross-reactive antibody responses against 4 heterologous H5N1 viruses. Excellent safety and tolerability were demonstrated., Conclusions: Point-of-use mixing of H5N1 antigen and MF59 adjuvant achieved target antibody titers in a high percentage of subjects and was safe. The feasibility of the point-of-use mixing should be studied further.

A novel series of barbituric acid derivatives were identified as selective inhibitors of alpha4beta7 MAdCAM (mucosal addressin cell adhesion molecule-1) interactions via a high throughput screening exercise. These inhibitors were optimized to submicromolar potencies in whole cell adhesion assays, retaining their selectivity over alpha4beta1 VCAM.

Background: Although preclinical preceptorships for medical students during the first 2 years are now common, little is known about how well the curricular objectives can be met in clinical training sites., Purpose: To evaluate whether a clinical encounter system can help align preclinical preceptorship experiences with the core curriculum., Methods: Using a PDA documentation system, 27 students collected student-preceptor-patient encounter information on all patients (N = 2,953) during a 2-year clinical training course. We compared Years 1 and 2 teaching and learning processes, common symptoms seen, and counseling skills performed and examined how well these clinical experiences aligned with the curricular goals., Results: The majority of encounters in Year 1 involved the student observing the preceptor perform a history (47%) or physical exam (40%). In Year 2, there was a shift to student and preceptor both participating in the history (Year 1, 12%; Year 2, 24%; p = .004) and physical exam (Year 1, 34%; Year 2, 47%; p = .002). Cardiovascular; pulmonary; and head, eyes, ears, nose, and throat examinations were most common in Year 1 and increased in Year 2. Genitourinary, gynecologic, and neurological examinations occurred least often, and only the neurological examinations increased significantly in Year 2. Overall, at least 75% of students could find opportunities in Years 1 and 2 to achieve the majority of curricular goals., Conclusions: Knowing what students experience at their preceptor sites is vital for clinical skills course evaluation. Student-preceptor-patient encounter data should be used to complement other course evaluations to aid curriculum planning and decrease variability in student experiences.

Purpose: Many medical schools have revised their curricula to include longitudinal clinical training in the first and second years, placing an extra burden on academic teaching faculty and expanding the use of community-based preceptors for clinical teaching. Little is known about the impact of different learning settings on clinical skills development., Method: In 2002-03 and 2003-04, the authors evaluated the clinical skills of two sequential cohorts of second-year medical students at Dartmouth Medical School (n = 155) at the end of a two-year longitudinal clinical course designed to prepare them for their clerkship year. Students' objective structured clinical examination (OSCE) scores were compared on a cardiopulmonary and an endocrine case according to precepting sites (academic medical center [AMC] clinics, AMC-affiliated office-based clinics, or community-based primary care offices) and core communication, history taking, physical examination, and patient education skills were assessed. Study groups were compared using descriptive statistics and analysis of variance (mixed model)., Results: Ninety-five students (61%) had community-based preceptors, 31 (20%) AMC clinic-based preceptors, and 29 (19%) AMC-affiliated office-based preceptors. Students' performances did not differ among clinical learning sites with overall scores in the cardiopulmonary case of 61.2% in AMC clinics, 63.3% in office-based AMC-affiliated clinics, and 64.9% in community-based offices (p = .20). Scores in the endocrine case similarly did not differ with overall scores of 65.5% in AMC clinics, 68.5% in office-based AMC-affiliated clinics, and 66.4% in community-based offices (p = .59)., Conclusions: Students' early clinical skill development is not influenced by educational setting. Thus, using clinicians for early clinical training in any of these settings is appropriate.