Positive perspectives of primary care professionals towards patients in complex and challenging social situations in Japan: An educational opportunity.

INTRODUCTION: Although primary care professionals often encounter difficulties when attending to patients in complex and challenging social situations (CCSS), little is known about how professionals cultivate an optimistic approach to caring for patients in CCSS. This study aims to recruit professionals who exhibit a passion for seeing patients in CCSS, to gain insights into their positive attitude. METHODS: We conducted a qualitative study in Japan of 30 primary care professionals: 15 physicians and 15 non-physician professionals (nurses, medical social workers and medical clerks). We performed online in-depth interviews and employed a thematic analysis utilising the framework approach to identify how the participants felt a passion for seeing patients in CCSS. RESULTS: Two themes emerged about the passion: (i) the joy derived from interacting with patients and (ii) the joy derived from professional growth or development. Participants expressed curiosity about their patients, found happiness in the journey with them and established irreplaceable relationships. Concurrently, participants noted professional growth as expert generalists, and their team developed collaboration and competency through accumulating experience and learning. These two domains of joy were intricately interconnected. In addition, several factors related to developing, maintaining and spreading the positive attitude were identified. DISCUSSION: This study described the positive attitude of primary care professionals towards engaging with patients in CCSS. Despite the inherent challenges, these professionals demonstrated vibrancy and pleasure in their interactions with patients and their professional development. Workplace culture including team-based support and continuous learning is important in fostering and maintaining such an attitude.

Machine learning for individualized prediction of hepatocellular carcinoma development after the eradication of hepatitis C virus with antivirals.

BACKGROUND AND AIMS: Accurate risk stratification for hepatocellular carcinoma (HCC) after achieving a sustained viral response (SVR) is necessary for optimal surveillance. We aimed to develop and validate a machine learning (ML) model to predict the risk of HCC after achieving an SVR in individual patients. METHODS: In this multicenter cohort study, 1742 patients with chronic hepatitis C who achieved an SVR were enrolled. Five ML models were developed including DeepSurv, gradient boosting survival analysis, random survival forest (RSF), survival support vector machine, and a conventional Cox proportional hazard model. Model performance was evaluated using Harrel' c-index and was externally validated in an independent cohort (977 patients). RESULTS: During the mean observation period of 5.4 years, 122 patients developed HCC (83 in the derivation cohort and 39 in the external validation cohort). The RSF model showed the best discrimination ability using seven parameters at the achievement of an SVR with a c-index of 0.839 in the external validation cohort and a high discriminative ability when the patients were categorized into three risk groups (P <0.001). Furthermore, this RSF model enabled the generation of an individualized predictive curve for HCC occurrence for each patient with an app available online. CONCLUSIONS: We developed and externally validated an RSF model with good predictive performance for the risk of HCC after an SVR. The application of this novel model is available on the website. This model could provide the data to consider an effective surveillance method. Further studies are needed to make recommendations for surveillance policies tailored to the medical situation in each country. IMPACT AND IMPLICATIONS: A novel prediction model for HCC occurrence in patients after hepatitis C virus eradication was developed using machine learning algorithms. This model, using seven commonly measured parameters, has been shown to have a good predictive ability for HCC development and could provide a personalized surveillance system.

Defining the observable processes of patient care related to social determinants of health.

INTRODUCTION: An understanding of social determinants of health (SDH) and patients' social circumstances is recommended to deliver contextualised care. However, the processes of patient care related to SDH in clinical settings have not been described in detail. Observable practice activities (OPAs) are a collection of learning objectives and activities that must be observed in daily practice and can be used to describe the precise processes for professionals to follow in specific situations (process OPA.) METHODS: We used a modified Delphi technique to generate expert consensus about the process OPA for patient care related to SDH in primary care settings. To reflect the opinions of various stakeholders, the expert panel comprised clinical professionals (physicians, nurses, public health nurses, social workers, pharmacists and medical clerks), residents, medical students, researchers (medical education, health care, sociology of marginalised people), support members for marginalised people and patients. The Delphi rounds were conducted online. In Round 1, a list of potentially important steps in the processes of care was distributed to panellists. The list was modified, and one new step was added. In Round 2, all steps were acknowledged with few modifications. RESULTS: Of 63 experts recruited, 61 participated, and all participants completed the Delphi rounds. A total of 14 observable steps were identified, which were divided into four components: communication, practice, maintenance and advocacy. The importance of ongoing patient-physician relationships and collaboration with professionals and stakeholders was emphasised for the whole process of care. DISCUSSION: This study presents the consensus of a variety of experts on the process OPA for patient care related to SDHs. Further research is warranted to investigate how this Communication-Practice-Maintenance-Advocacy framework could affect medical education, quality of patient care, and patient outcomes.

Current perception of social accountability of medical schools in Japan: A qualitative content analysis.

INTRODUCTION: The concept of social accountability in medical schools is globally accepted, but data regarding Japanese medical schools are lacking and unclear. This study aimed to elucidate the perception of social accountability of medical schools in Japan and compare this to global frameworks. METHODS: A document on Japanese medical accreditation standards (Basic Medical Education: Japanese Specifications WFME Global Standards for Quality Improvement) was used for this study. We included 45 medical schools in a qualitative content analysis done via inductive category formation. The documents were also assessed using the social obligation scale. RESULTS: Three main categories and 15 categories were identified. The three main categories were as follows: Issues in society, Quality assurance of medical school, and Improvement of individual quality. Most categories were common to those in global frameworks, but some were characteristic of the Japanese context. The distribution of schools on the social obligation scale in six elements varied mainly 'from responsibility to responsiveness' or equal unless the elements were promoted by national policy. CONCLUSIONS: The social accountability of Japanese medical schools is mostly common with the global frameworks. Our findings will help the social accountability of medical schools to become better understood and developed beyond contextual borders.

Impact of value similarity on social trust in medical students: a cross-sectional web survey.

BACKGROUND: Social trust in medical students is trust in the cluster of medical students and not individual medical students. Social trust in medical students seems critical in clinical practice since citizens often face unknown medical students for the first time. However, most previous research has focused on interpersonal trust in particular medical professions, and social trust in medical students has not been addressed sufficiently. In social science, the Salient Value Similarity model has demonstrated that the value similarity between professionals and citizens is associated with social trust. This research aimed to explore the relationship between social trust in medical students and the perception of value similarity. This study also aimed to determine whether the information of medical students strengthens social trust in them. METHODS: We conducted a cross-sectional study to investigate how the perception of value similarity affects social trust. The participants answered the social trust questionnaires before and after reading a brief summary of the medical education curriculum and certification via the internet in Japan. The model structure of social trust in medical students, including the perception of value similarity, was investigated using SEM. A paired t-test was used to examine the effect of informing citizens about the knowledge, skills, and professionalism requirements of students attending medical school on social trust by reading the brief summary. RESULTS: The study included 658 participants, who all answered a web questionnaire. Social trust in medical students was associated with the perception of ability and value similarity. Social trust in medical students, the perception of ability, and value similarity were improved by information about medical students. CONCLUSIONS: The perception of ability and value similarity seem to affect social trust in medical students. Information on medical education regarding the knowledge, skills, and professionalism of medical students may improve social trust in these students. Further research is required to sophisticate the model of social trust in medical students by exploring social trust in the medical students' supervisors in clinical settings.

Development and assessment of a vaccine administration training course for medical students.

BACKGROUND: Vaccine administration skills are very important for physicians, especially in the era of global pandemics. However, medical students have reported that practical sessions to develop these skills are insufficient. Therefore, the aim of our study was to develop a vaccination training course for medical students. We also examined its educational effectiveness. METHODS: 5th- and 6th-year medical students at the University of Tokyo were recruited to attend the vaccine administration training course in 2021. These students were our study participants. Our course consisted of an orientation part, which included a lecture on the indications, adverse events, and vaccination techniques of flu vaccines and practice on a simulator, and a main part in which the staff of the University of Tokyo Hospital were actually vaccinated. Before and after the main part of the course, study participants completed an online questionnaire that assessed their confidence in vaccine administration technique through a five-point Likert scale. We also surveyed their feedback about the course content and process. At the beginning and end of the main part, their technical competence in vaccination was assessed by two independent doctors. These doctors used a validated checklist scale (ranging from 16 to 80) and a global rating scale (ranging from 0 to 10). We used their mean scores for analysis. The quantitative data were analyzed through the Wilcoxon signed-rank test. For the qualitative data of the questionnaire, thematic analysis was conducted. RESULTS: All 48 course participants participated in our study. Participants' confidence in vaccination technique (Z = -5.244, p < 0.05) and vaccination skill significantly improved (checklist rating: Z = -5.852, p < 0.05; global rating: Z = -5.868, p < 0.05). All participants rated the course as, "overall educational." Our thematic analysis identified four emerging themes: interest in medical procedures, efficacy of supervision and feedback, efficacy of "near-peer" learning, and very instructive course. CONCLUSIONS: In our study, we developed a vaccine administration course for medical students, assessed their vaccination techniques and confidence in those techniques, and investigated their perceptions of the course. Students' vaccination skills and confidence improved significantly after the course, and they positively evaluated the course based on a variety of factors. Our course will be effective in educating medical students about vaccination techniques.

Organoid-based ex vivo reconstitution of Kras-driven pancreatic ductal carcinogenesis.

The organoid culture technique has been recently applied to modeling carcinogenesis in several organs. To further explore its potential and gain novel insights into tumorigenesis, we here investigated whether pancreatic ductal adenocarcinoma (PDA) could be generated as subcutaneous tumors in immunocompromised nude mice, by genetic engineering of normal organoids. As expected, acute induction of KrasG12Din vitro occasionally led to development of tiny nodules compatible with early lesions known as pancreatic intraepithelial neoplasia (PanIN). KrasG12D-expressing cells were enriched after inoculation in the subcutis, yet proved rather declined during culture, suggesting that its advantage might depend on surrounding environments. Depletion of growth factors or concurrent Trp53 deletion resulted in its robust enrichment, invariably leading to development of PanIN or large high-grade adenocarcinoma, respectively, consistent with in vivo mouse studies for the same genotype. Progression from PanIN was also recapitulated by subsequent knockdown of common tumor suppressors, whereas the impact of Tgfbr2 deletion was only partially recapitulated, illustrating genotype-dependent requirement of the pancreatic niche for tumorigenesis. Intriguingly, analysis of tumor-derived organoids revealed that KrasG12D-expressing cells with spontaneous deletion of wild-type Kras were positively selected and exhibited an aging-related mutation signature in nude mice, mirroring the pathogenesis of human PDA, and that the sphere-forming potential and orthotopic tumorigenicity in syngenic mice were significantly augmented. These observations highlighted the relevance of the subcutis of nude mice in promoting PDA development despite its ectopic nature. Taken together, pancreatic carcinogenesis could be considerably recapitulated with organoids, which would probably serve as a novel disease model.

Kras-driven heterotopic tumor development from hepatobiliary organoids.

Cancers arising from the biliary tract are refractory to conventional therapies, requiring the development of novel therapeutics. However, only a limited number of genetically engineered mouse models have been created, partly because of time-consuming work required. Besides, liver-specific gene manipulation mostly resulted in concurrent development of hepatocellular carcinoma, another type of liver cancer, and gallbladder-restricted gene targeting is still not feasible. Consequently, establishment of cancer type-specific disease modeling remains a technical challenge. To address this issue, we took an alternative cell-based approach to quickly induce tumorigenesis ex vivo. Specifically, murine primary organoids from liver and gallbladder were transduced with lentiviral vectors to reconstitute genetic alterations common in biliary tract cancers, followed by inoculation in immunodeficient mice. Although any single genetic alteration did not induce tumors, mutant Kras and repression of major tumor suppressors cooperated for tumor development within 2 months. Induced lesions varied among normal, dysplastic and papillary lesions to adenocarcinoma, recapitulating multistep tumorigenesis even in a heterotopic situation. We further demonstrated that two putative oncogenes in intrahepatic cholangiocellular carcinoma, mutant Pik3ca and FGFR2-AHCYL1 fusion, were rather modest drivers for liver-derived organoids, probably requiring additional mutations or hepatic niche to robustly induce full-blown tumors. Thus, we showed that cancer cells could be readily generated from primary cells in the biliary tract, at least in cases where genetic factors play dominant roles. Collectively, this study will likely contribute to gaining mechanistic insights into biliary carcinogenesis and providing valuable resources for drug discovery.

Genomic profiles of colorectal carcinoma with liver metastases and newly identified fusion genes.

Every year, approximately 1.2 million cases of colorectal carcinoma (CRC) are newly diagnosed worldwide. Although metastases to distant organs are often fatal complications of CRC, little information is known as to how such metastatic lesions are formed. To reveal the genetic profiles for CRC metastasis, we conducted whole-exome RNA sequencing on CRC tumors with liver metastasis (LM) (group A, n = 12) and clinical stage-matched larger tumors without LM (group B, n = 16). While the somatic mutation profiles were similar among the primary tumors and LM lesions in group A and the tumors in group B, the A-to-C nucleotide change in the context of "AAG" was only enriched in the LM regions in group A, suggesting the presence of a DNA damage process specific to metastasis. Genes already known to be associated with CRC were mutated in all groups at a similar frequency, but we detected somatic nonsynonymous mutations in a total of 707 genes in the LM regions, but not in the tumors without LM. Signaling pathways linked to such "LM-associated" genes were overrepresented for extracellular matrix-receptor interaction or focal adhesion. Further, fusions of the ADAP1 (ArfGAP with dual PH domain 1) were newly identified in our cohort (3 out of 28 patients), which activated ARF6, an ADAP1-substrate. Infrequently, mutated genes may play an important role in metastasis formation of CRC. Additionally, recurrent ADAP1 fusion genes were unexpectedly discovered. As these fusions activate small GTPase, further experiments are warranted to examine their contribution to CRC carcinogenesis.