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To assess the relationship between polydoctoring and patient outcomes, we conducted a retrospective cohort study using a Japanese population-based dataset from April 2014 to December 2022. Overall, 2,338,965 patients aged 75–89 years with at least two chronic conditions were included. Polydoctoring was assessed by the number of regularly visited facilities (RVFs). The primary outcome was all-cause mortality, with secondary outcomes being all-cause hospitalizations, hospitalizations for ambulatory care-sensitive conditions (ACSCs), and outpatient costs. During the study period, 14.5% of participants died, 52.2% were hospitalized, and 12.5% experienced ACSC-related hospitalizations. Patients without RVFs had the highest mortality risk (HR: 3.23, 95% CI: 3.14–3.33), while those with ≥ 5 RVFs had the lowest (HR: 0.67, 95% CI: 0.62–0.73). ACSC-related hospitalizations were U-shaped, with increased risk at ≥ 5 RVFs (HR: 1.13, 95% CI: 1.06–1.22). Outpatient costs increased 3.21 times for ≥ 5 RVFs compared to 1 RVF. Polydoctoring was associated with reduced mortality but higher hospitalization rates and costs, with an optimal RVF range of 2–3 which minimized ACSC-related admissions. These findings emphasize the need for strategies that balance the benefits and costs of polydoctoring to support sustainable healthcare through improved care coordination and resource management for aging populations.

Purpose Ambiguity tolerance specific to the clinical context – in contrast to ambiguity tolerance as a personality trait – may vary with experience and has received considerable attention. Although this tolerance appears to be related to burnout and work engagement, few studies have examined this association among physicians. Thus, we aimed to examine the relationships between clinical context-specific ambiguity tolerance, burnout, and work engagement among physicians in Japan. Methods We conducted a nationwide cross-sectional study in Japan. We invited family physicians from 14 family medicine residency programs and physicians with specialties other than family medicine from monitors of an Internet survey company to participate in the study. We measured ambiguity tolerance in the clinical context using the Japanese version of the Tolerance of Ambiguity in Medical Students and Doctors (J-TAMSAD) scale, burnout using the Japanese version of the Burnout Assessment Scale (BAT-J), and work engagement using the Utrecht Work Engagement Scale (UWES). We performed a multivariable linear regression analysis to determine whether the J-TAMSAD scale score was associated with the BAT-J and UWES scores. Results 383 respondents were included in the analysis. After adjustment for possible confounders, clinical context-specific ambiguity tolerance showed a dose-dependent negative association with burnout (adjusted mean difference  -0.39, 95% confidence interval (CI) -0.56 to -0.22 for the highest J-TAMSAD score quartile compared with the lowest). Ambiguity tolerance in the clinical context also showed a dose-dependent positive association with work engagement (adjusted mean difference 0.83, 95% CI 0.49 to 1.16 for the highest J-TAMSAD score quartile compared with the lowest). Conclusions Our study showed that tolerance for ambiguity in the clinical context was negatively associated with burnout, and positively associated with work engagement. These findings will be useful in developing interventions aimed at preventing burnout and promoting work engagement among physicians.

Background Understanding social determinants of health is essential for medical education, particularly in complex urban settings. This study evaluated a fieldwork-based community diagnosis program designed to help medical students identify community health issues, appreciate diverse social contexts, and integrate theoretical frameworks into practical learning. Methods The program was integrated into a two-week general medicine clerkship at X Medical School in Tokyo in 2022–2023. It included an orientation on ecological systems theory and phenomenological reduction, followed by urban fieldwork, student presentations, peer and faculty feedback, and a final report. A realist approach using Context-Mechanism-Outcome (CMO) framework guided the evaluation, focusing on how contextual factors influenced learning mechanisms to produce specific outcomes. Data sources included students’ reports, reflective writings, and feedback session transcripts. Qualitative analysis was conducted to identify patterns of learning and interaction. Students’ understanding of community health and ability to apply theoretical models were assessed using structured rubrics. Results The program significantly improved students’ ability to observe, analyze, and interpret complex urban community dynamics. Orientation sessions helped students overcome theory-laden biases and expand their observational skills. Fieldwork, coupled with iterative feedback, facilitated double-loop learning, enabling students to reassess assumptions and refine their perspectives. Positionality theory encouraged reflection on power dynamics, leading students to critically examine implicit biases and understand the perspectives of marginalized populations. Through phenomenological reduction, students recognized biases in their biomedical training and shifted toward a holistic understanding of community health, encompassing ecological and social determinants. Peer and faculty feedback promoted intersubjectivity, allowing students to develop a layered appreciation of urban diversity and social complexity. Students reported an increased ability to connect theoretical knowledge with real-world health disparities, proposing actionable, sustainable interventions for urban communities. Conclusions This realist approach demonstrated that integrating fieldwork with reflective learning and theory-based frameworks can foster transformative educational experiences. The findings highlight the importance of incorporating community-based programs into medical curricula to prepare future physicians to address health disparities and complex social determinants effectively.

Background Gastric cancer risk can be accurately predicted by measuring the methylation level of a single marker gene in gastric mucosa. However, the mechanism is still uncertain. We hypothesized that the methylation level measured reflects methylation alterations in the entire genome (methylation burden), induced by Helicobacter pylori ( H. pylori ) infection, and thus cancer risk. Methods Gastric mucosa of 15 healthy volunteers without H. pylori infection (G1), 98 people with atrophic gastritis (G2), and 133 patients with gastric cancer (G3) after H. pylori eradication were collected. Methylation burden of an individual was obtained by microarray analysis as an inverse of the correlation coefficient between the methylation levels of 265,552 genomic regions in the person’s gastric mucosa and those in an entirely healthy mucosa. Results The methylation burden significantly increased in the order of G1 (n = 4), G2 (n = 18), and G3 (n = 19) and was well correlated with the methylation level of a single marker gene (r = 0.91 for miR124a-3 ). The average methylation levels of nine driver genes tended to increase according to the risk levels ( P  = 0.08 between G2 vs G3) and was also correlated with the methylation level of a single marker gene (r = 0.94). Analysis of more samples (14 G1, 97 G2, and 131 G3 samples) yielded significant increases of the average methylation levels between risk groups. Conclusions The methylation level of a single marker gene reflects the methylation burden, which includes driver gene methylation, and thus accurately predicts cancer risk.

Background Ambiguity tolerance in the clinical context is increasingly recognized as essential for physicians to work as professionals. However, the relationship between specialty and ambiguity tolerance in the clinical context has been understudied. Here, we investigated the association between specialty and ambiguity tolerance in the clinical context, focusing on differences between family physicians (FPs) and non‐FPs. Methods We performed a nationwide cross‐sectional study in Japan. We asked FPs from 14 family medicine residency programs across Japan and non‐FPs from monitors of an internet survey company in Japan to participate in the study. We assessed their tolerance for ambiguity using the Japanese version of the Tolerance for Ambiguity in Medical Students and Doctors (J‐TAMSAD) scale. Results In total, 388 physicians (178 FPs and 210 non‐FPs) completed our anonymous online survey and were included in the analysis. After adjustment for possible confounders (gender and postgraduate years), FPs had higher J‐TAMSAD scale scores than internists/pediatricians, surgeons, and physicians with other specialties, meaning that FPs had greater ambiguity tolerance. Conclusions This study reveals that FPs had greater tolerance for ambiguity in the clinical context than non‐FPs. Our findings suggest that there may be a need to increase non‐FP's tolerance for ambiguity specific to the clinical context through educational interventions, since ambiguity is inherent and growing in medicine today. FPs and non‐FPs should work together to complement each other's strengths, rather than simply improving the training of non‐FPs.

Focal seizures, characterized by excessive electrical excitation in a brain region, present diagnostic challenges due to diverse manifestations, particularly with non-motor symptoms. Here, we present a 69-year-old Japanese woman experiencing unexplained recurrent episodes of sweating, chills, and shivering. Despite exhaustive investigations that identified no abnormalities, her symptoms remained unalleviated by symptomatic treatments. The episodic nature of her presentations subsequently prompted a clinical suspicion of seizures, leading to further neurological evaluations. Magnetic resonance imaging (MRI) of the brain and electroencephalography (EEG) revealed chronic ischemic changes in the cerebral white matter and intermittent sharp and slow wave bursts in the frontal regions. These findings led to a diagnosis of focal seizures manifesting as autonomic symptoms. The patient's symptoms were successfully treated with carbamazepine. This case illustrates the importance of considering non-motor focal seizures in patients with episodic symptoms, even when routine tests show no abnormalities.

Background The need to engage medical students in understanding the social and environmental determinants of health in disparate communities is increasing. However, previous reviews have noted the limited community diagnosis programs and program evaluation. Given the feasibility of the programs, it is expected to be widely available online. Therefore, this study used a realist approach to identify learning patterns through an online community diagnosis program, namely context (C), mechanism (M), and outcomes (O) patterns. Methods A 2-week general medicine clinical practice program was conducted for 4 th - and 5 th -year medical students at a medical university in Japan. The program included a one-hour zoom-based lecture, feedback for students on their presentations on community diagnosis, and a structural report on community diagnosis. We developed the program based on variation theory, which views discernment and variation in situations having time, space, and social dimensions as core learning. The students' reflections on their learning through the program were thematically analyzed through CMO perspectives. The realist approach used in the online diagnosis program evaluation allows us to explore, test, and refine what mechanisms work under what conditions (context) and with what interventions (including opportunities and resources), from which we can describe iteratively explainable results. Results First, the medical students, who spent most of their time in the limited residential areas they lived in, discovered the characteristics of their own community by discovery learning and comparison among peers. Second, they increased their intrinsic interest in the community by discerning specific issues in their familiar community through community diagnosis. Third, they valued community diagnosis by identifying relationships between local data on health issues under their learning responsibility. Fourth, they become more flexible in their thinking and created new knowledge that would fit the local community, and their reflection on themselves was encouraged. Conclusion In this online community diagnosis program, medical students learned about the community through four types of learning patterns. Medical students may develop an understanding of community with interest using variation theory as a program development perspective and cognitive flexibility theory surrounding the essential ambiguity and abstraction of community.

Background The profiles of genetic and epigenetic alterations in cancer-related pathways are considered to be useful for selection of patients likely to respond to specific drugs, including molecular-targeted and epigenetic drugs. In this study, we aimed to characterize such profiles in gastric cancers (GCs). Methods Genetic alterations of 55 cancer-related genes were analyzed by a benchtop next-generation sequencer. DNA methylation statuses were analyzed by a bead array with 485,512 probes. Results The WNT pathway was activated by mutations of CTNNB1 in 2 GCs and potentially by aberrant methylation of its negative regulators, such as DKK3 , NKD1 , and SFRP1 , in 49 GCs. The AKT/mTOR pathway was activated by mutations of PIK3CA and PTPN11 in 4 GCs. The MAPK pathway was activated by mutations and gene amplifications of ERBB2 , FLT3 , and KRAS in 11 GCs. Cell-cycle regulation was affected by aberrant methylation of CDKN2A and CHFR in 13 GCs. Mismatch repair was affected by a mutation of MLH1 in 1 GC and by aberrant methylation of MLH1 in 2 GCs. The p53 pathway was inactivated by mutations of TP53 in 19 GCs and potentially by aberrant methylation of its downstream genes in 38 GCs. Cell adhesion was affected by mutations of CDH1 in 2 GCs. Conclusions Genes involved in cancer-related pathways were more frequently affected by epigenetic alterations than by genetic alterations. The profiles of genetic and epigenetic alterations are expected to be useful for selection of the patients who are likely to benefit from specific drugs.

Background Nodular gastritis (NG) is characterized by marked antral lymphoid follicle formation, and is a strong risk factor for diffuse-type gastric cancer in adults. However, it is unknown whether aberrant DNA methylation, which is induced by atrophic gastritis (AG) and is a risk for gastric cancer, is induced by NG. Here, we analyzed methylation induction by NG. Methods Gastric mucosal samples were obtained from non-cancerous antral tissues of 16 NG and 20 AG patients with gastric cancer and 5 NG and 6 AG patients without, all age- and gender-matched. Genome-wide methylation analysis and expression analysis were conducted by a BeadChip array and RNA-sequencing, respectively. Results Clustering analysis of non-cancerous antral tissues of NG and AG patients with gastric cancer was conducted using methylation levels of 585 promoter CpG islands (CGIs) of methylation-resistant genes, and a large fraction of NG samples formed a cluster with strong methylation induction. Promoter CGIs of CDH1 and DAPK1 tumor-suppressor genes were more methylated in NG than in AG. Notably, methylation levels of these genes were also higher in the antrum of NG patients without cancer. Genes related to lymphoid follicle formation, such as CXCL13 / CXCR5 and CXCL12 / CXCR4 , had higher expression in NG, and genes involved in DNA demethylation TET2 and IDH1 , had only half the expression in NG. Conclusions Severe aberrant methylation, involving multiple tumor-suppressor genes, was induced in the gastric antrum and body of patients with NG, in accordance with their high gastric cancer risk.

BackgroundPrecision cancer risk stratification for gastric cancer is urgently needed for the growing number of healthy people after Helicobacter pylori eradication. The epimutation burden in non-malignant tissues has been associated with cancer risk in multiple cross-sectional studies.ObjectiveTo confirm the clinical usefulness of a DNA methylation marker for epimutation burden, and to identify a cut-off methylation level for a super-high-risk population.DesignHealthy people after H. pylori eradication with open-type atrophy were prospectively recruited. DNA methylation levels of a marker gene, RIMS1, were measured in biopsy specimens from gastric antrum and body. The primary endpoint was the incidence rate of gastric cancer in quartiles of the methylation levels.Results1624 participants had at least one endoscopic follow-up with a median follow-up of 4.05 years, and a primary gastric cancer developed in 27 participants. The highest quartile of RIMS1 methylation levels had a higher incidence rate (972.8 per 100 000 person-years) than the lowest quartile (127.1). Cox regression analysis revealed a univariate HR of 7.7 (95% CI 1.8–33.7) and an age- and sex-adjusted HR of 5.7 (95% CI 1.3–25.5). As a secondary objective, a cut-off methylation level of 25.7% (95% CI 1.7–7.7) was obtained to identify a population with a super-high risk based on the number needed to screen of 1000.ConclusionA DNA methylation marker can risk-stratify healthy people after H. pylori eradication even though all of them have clinically high risk. Individuals with super-high risk will need more frequent gastric cancer screening than currently recommended.Trial registration numberUMIN-CTR000016894.