BACKGROUND: Low plasma levels of eicosapentaenoic acid (EPA) are associated with cardiovascular events. This trial aimed to assess the clinical benefits of icosapent ethyl in patients with coronary artery disease, a low EPA/arachidonic acid (AA) ratio, and statin treatment. METHODS: In this prospective, multicenter, randomized, open-label, blinded end-point study, patients with stable coronary artery disease and a low EPA/AA ratio (<0.4) were randomized to EPA (1800 of icosapent ethyl administered daily) or control group. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, unstable angina pectoris, and coronary revascularization. The secondary composite end points of coronary events included sudden cardiac death, fatal and nonfatal myocardial infarction, unstable angina requiring emergency hospitalization and coronary revascularization, or coronary revascularization. RESULTS: Overall, 3884 patients were enrolled at 95 sites in Japan. Among them, 2506 patients had a low EPA/AA ratio, and 1249 and 1257 patients were randomized to the EPA and control group, respectively. The median EPA/AA ratio was 0.243 (interquartile range, 0.180–0.314) and 0.235 (interquartile range, 0.163–0.310) in the EPA and control group, respectively. Over a median period of 5 years, the primary end point occurred in 112 of 1225 patients (9.1%) and 155 of 1235 patients (12.6%) in the EPA and control group, respectively (hazard ratio, 0.79 [95% CI, 0.62–1.00]; P =0.055). Meanwhile, the secondary composite end point of coronary events in the EPA group was significantly lower (81/1225 [6.6%] versus 120/1235 [9.7%] patients; hazard ratio, 0.73 [95% CI, 0.55–0.97]). Adverse events did not differ between the groups, but the rate of new-onset atrial fibrillation was significantly higher in the EPA group (3.1% versus 1.6%; P =0.017). CONCLUSIONS: Icosapent ethyl treatment resulted in a numerically lower risk of cardiovascular events that did not reach statistical significance in patients with chronic coronary artery disease, a low EPA/AA ratio, and statin treatment. REGISTRATION: URL: https://www.umin.ac.jp/ctr/ ; Unique identifier: UMIN000012069.

INTRODUCTION: Few reports exist regarding the therapeutic effects of probiotics on chronic constipation in elderly individuals. This study evaluated the effects of Bifidobacterium longum BB536 in elderly individuals with chronic constipation. METHODS: This was a randomized, double-blind placebo-controlled, parallel-group superiority trial in Japan (UMIN 000033031). Eighty older adults diagnosed with chronic constipation were randomly assigned (1:1) to receive either probiotics (B. longum BB536, 5 × 10¹⁰ colony-forming unit, n = 39) or placebo (n = 41) once daily for up to 4 weeks. The severity of constipation was evaluated using the Constipation Scoring System. The primary end point was the difference in the changes from baseline in the constipation scoring system total score between the 2 groups at week 4. RESULTS: A total of 79 patients (mean age of 77.9 years), including 38 patients in the BB536 group and 41 in the placebo group, completed the study. The primary end point was not significant (P = 0.074), although there was significant improvement (P < 0.01) in the BB536 group from baseline to week 4, but there were no significant changes in the placebo group. There was a significant difference and a tendency toward a difference in the changes from baseline on the stool frequency (P = 0.008) and failure of evacuation (P = 0.051) subscales, respectively, at week 4 between the 2 groups. Few adverse events related to the probiotics were observed. DISCUSSION: The primary end points were not significant. However, probiotic supplementation significantly improved bowel movements. These results suggest that B. longum BB536 supplementation is safe and partially effective for improving chronic constipation in elderly individuals.

Background: The reliability of GPT-4, a state-of-the-art expansive language model specializing in clinical reasoning and medical knowledge, remains largely unverified across non-English languages. Objective: This study aims to compare fundamental clinical competencies between Japanese residents and GPT-4 by using the General Medicine In-Training Examination (GM-ITE). Methods: We used the GPT-4 model provided by OpenAI and the GM-ITE examination questions for the years 2020, 2021, and 2022 to conduct a comparative analysis. This analysis focused on evaluating the performance of individuals who were concluding their second year of residency in comparison to that of GPT-4. Given the current abilities of GPT-4, our study included only single-choice exam questions, excluding those involving audio, video, or image data. The assessment included 4 categories: general theory (professionalism and medical interviewing), symptomatology and clinical reasoning, physical examinations and clinical procedures, and specific diseases. Additionally, we categorized the questions into 7 specialty fields and 3 levels of difficulty, which were determined based on residents’ correct response rates. Results: Upon examination of 137 GM-ITE questions in Japanese, GPT-4 scores were significantly higher than the mean scores of residents (residents: 55.8%, GPT-4: 70.1%; P<.001). In terms of specific disciplines, GPT-4 scored 23.5 points higher in the “specific diseases,” 30.9 points higher in “obstetrics and gynecology,” and 26.1 points higher in “internal medicine.” In contrast, GPT-4 scores in “medical interviewing and professionalism,” “general practice,” and “psychiatry” were lower than those of the residents, although this discrepancy was not statistically significant. Upon analyzing scores based on question difficulty, GPT-4 scores were 17.2 points lower for easy problems (P=.007) but were 25.4 and 24.4 points higher for normal and difficult problems, respectively (P<.001). In year-on-year comparisons, GPT-4 scores were 21.7 and 21.5 points higher in the 2020 (P=.01) and 2022 (P=.003) examinations, respectively, but only 3.5 points higher in the 2021 examinations (no significant difference). Conclusions: In the Japanese language, GPT-4 also outperformed the average medical residents in the GM-ITE test, originally designed for them. Specifically, GPT-4 demonstrated a tendency to score higher on difficult questions with low resident correct response rates and those demanding a more comprehensive understanding of diseases. However, GPT-4 scored comparatively lower on questions that residents could readily answer, such as those testing attitudes toward patients and professionalism, as well as those necessitating an understanding of context and communication. These findings highlight the strengths and limitations of artificial intelligence applications in medical education and practice.

Background: Although general medicine (GM) faculty in Japanese medical schools have an important role in educating medical students, the importance of residents’ rotation training in GM in postgraduate education has not been sufficiently recognized in Japan. To evaluate the relationship between the rotation of resident physicians in the GM department and their In-Training Examination score.Methods: This study is a nationwide multi-center cross-sectional study in Japan. Participants of this study are Japanese junior resident physicians [postgraduate year (PGY)-1 and PGY-2] who took the General Medicine In-Training Examination (GM-ITE) in fiscal years 2016 to 2018 at least once (n = 11,244). The numbers of participating hospitals in the GM-ITE were 381, 459, and 503 in 2016, 2017, and 2018.The GM-ITE score consisted of four categories (medical interview/professionalism, symptomatology/clinical reasoning, physical examination/procedure, and disease knowledge). We evaluated relationship between educational environment (including hospital information) and the GM-ITE score.Results: A total of 4464 (39.7%) residents experienced GM department rotation training. Residents who rotated had higher total scores than residents who did not rotate (38.1 ± 12.1, 36.8 ± 11.7, and 36.5 ± 11.5 for residents who experienced GM rotation training, those who did not experience this training in hospitals with a GM department, and those who did not experience GM rotation training in hospitals without a GM department,p = 0.0038). The association between GM rotation and competency remained after multivariable adjustment in the multilevel model: the score difference between GM rotation training residents and non-GM rotation residents in hospitals without a GM department was estimated as 1.18 (standard error, 0.30,p = 0.0001), which was approximately half of the standard deviation of random effects due to hospital variation (estimated as 2.00).Conclusions: GM rotation training improved the GM-ITE score of residents and should be considered mandatory for junior residents in Japan.

Purpose: In Japan, the General Medicine In-training Examination (GM-ITE) was developed by a non-profit organization in 2012. The GM-ITE aimed to assess the general clinical knowledge among residents and to improve the training programs; however, it has not been sufficiently validated and is not used for high-stake decision-making. This study examined the association between GM-ITE and another test measure, the Professional and Linguistic Assessments Board (PLAB) 1 examination. Methods: Ninety-seven residents who completed the GM-ITE in fiscal year 2019 were recruited and took the PLAB 1 examination in Japanese. The association between two tests was assessed using the Pearson product-moment statistics. The discrimination indexes were also assessed for each question. Results: A total of 91 residents at 17 teaching hospitals were finally included in the analysis, of whom 69 (75.8%) were women and 59 (64.8%) were postgraduate second year residents. All the participants were affiliated with community hospitals. Positive correlations were demonstrated between the GM-ITE and the PLAB scores (r = 0.58, p < 0.001). The correlations between the PLAB score and the scores in GM-ITE categories were as follows: symptomatology/clinical reasoning (r = 0.54, p < 0.001), physical examination/procedure (r = 0.38, p < 0.001), medical interview/professionalism (r = 0.25, p < 0.001), and disease knowledge (r = 0.36, p < 0.001). The mean discrimination index of each question of the GM-ITE (mean ± SD; 0.23 ± 0.15) was higher than that of the PLAB (0.16 ± 0.16; p = 0.004). Conclusion: This study demonstrates incremental validity evidence of the GM-ITE to assess the clinical knowledge acquisition. The results indicate that GM-ITE can be widely used to improve resident education in Japan.

In prior myocardial infarction (PMI) patients, diabetes mellitus (DM), dyslipidemia, and hypertension increase the risk of secondary cardiovascular events. Although a decreased ratio of serum eicosapentaenoic acid (EPA) to arachidonic acid (AA; EPA/AA) has been shown to significantly correlate with the onset of acute coronary syndrome, the associations between polyunsaturated fatty acid (PUFA) levels and coronary risk factors in PMI patients have not been evaluated thoroughly. This study aimed to assess the associations between PUFAs levels and the risk factors in PMI patients. We enrolled 1733 patients with known PUFA levels who were treated in five divisions of cardiology in a metropolitan area of Japan, including 303 patients with PMI. EPA/AA and docosahexaenoic acid (DHA) to AA level ratio (DHA/AA) in patients with and without PMI were analyzed according to presence of coronary risk factors. Diabetes patients with PMI had significantly lower EPA/AA and DHA/AA than diabetes patients without PMI (EPA/AA: P 0.1 mg/dL), EPA/AA was low in individuals who also had PMI, whereas DHA/AA was not (EPA/AA, with PMI: 0.43 ± 0.24; without PMI: 0.53 ± 0.30, P < 0.05). Moreover, patients on statins had significantly lower DHA/AA ratios, whereas the EPA/AA ratio did not depend on statin use. Multiple regression analysis revealed that statin use in DM patients was associated with low DHA/AA but not EPA/AA. PMI patients with DM have low EPA/AA and DHA/AA. EPA/AA and DHA/AA are differently related to hs-CRP level in DM patients with PMI. Statin use can potentially affect DHA/AA but not EPA/AA, and therefore EPA/AA ratio is a better marker of assessment for cardiovascular events.