Efficacy and Concurrent Validity of Computerized Brain Training Based on Everyday Living (BTEL) Based on Instrumental Activities of Living for Cognitively Healthy Old Individuals: A Preliminary Study.

Background: Interventions to prevent or attenuate cognitive decline and dementia in older adults are becoming increasingly important. Recently, cognitive training exercise can be via computer or mobile technology for independent or home use. Recent meta-analysis has reported that Computerized Cognitive Training (CCT) is effective at enhancing cognitive function in healthy older and Alzheimer's disease adults, although little is known about individual characteristics of each computerized program. Objective: We developed a new CCT named Brain Training Based on Everyday Living (BTEL) to enhance cognitive capacity for Instrumental Activities of Daily Living (IADL). We aim to evaluate the efficacy of the BTEL among cognitively healthy old individuals and to explore its concurrent validity and construct concept. Methods: We conducted a double-blind study where 106 individuals aged 65 years and older (intervened = 53, control = 53) worked on the active and placebo tasks three times a week over three months (clinical trial: UMIN000048730). The main results were examined using ANCOVA and calculating correlation coefficients. Results: We found no effect on total score of the three tests; however, there was significant effect for the BTEL on: recognition in MMSE, and immediate recall in HDSR. The tasks are associated with prefrontal cortex. In addition, correlations indicated that each BTEL domain had some validity as a cognitive assessment tool. Different from previous CCT, we determined the neuropsychological characteristics of specific cognitive tasks of the BTEL to a certain degree. Conclusions: We found modest efficacy of the BTEL in cognitively healthy old individuals and confirmed its concurrent validity and the conceptual construct.

Changing trends in Japanese spotted fever epidemiology in Shimane, Japan: A two-decade retrospective study with emphasis on the COVID-19 pandemic era.

INTRODUCTION: The objective of this study is to evaluate the epidemiological characteristics of Japanese Spotted Fever (JSF) cases reported through the National Epidemiological Surveillance of Infectious Disease (NESID) system in Shimane Prefecture, Japan, from 2000 to 2022, encompassing the periods before and during the COVID-19 pandemic period. METHODS: A retrospective analysis was conducted on JSF cases reported to the NESID system in Shimane Prefecture between 2000 and 2022. Population data were obtained from the Statistical Information of Shimane. Poisson regression analysis was employed to examine the relationship between the annual prevalence rate of JSF and the COVID-19 pandemic. RESULTS: A total of 301 JSF cases were analyzed during the study period. Even the pre-COVID-19 pandemic period, a gradual and significant increase in the prevalence rate was observed (prevalence rate = 1.03, 95% CI: 1.01-1.05; p = 0.01), and a rapid increase was noted since 2020 (prevalence rate = 1.57, 95% CI: 1.39-1.78; p < 0.01). The slope during the pre-COVID-19 pandemic period was estimated to have significantly increased (p < 0.01). CONCLUSIONS: Our findings suggest that while the prevalence rate of JSF had exhibited a slight increase in the years preceding the COVID-19 pandemic, it demonstrated a more significant increase following the pandemic in Shimane Prefecture. JSF has increased since 2020 and may be linked to COVID-19 pandemic. The COVID-19 pandemic has had a substantial impact on global health, underscoring the importance of investigating the prevalence of specific infectious diseases and other health-related indicators to accurately assess the pandemic's impact.

Synergistic effect of independent risk factors for post-endoscopic retrograde cholangiopancreatography pancreatitis: a multicenter retrospective study in Japan.

Background/Aims: This study aimed to examine the synergistic effect of independent risk factors on post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). Methods: This multicenter retrospective study included 1,273 patients with native papillae who underwent ERCP for bile dust stones in Japan. Independent PEP risk factors were identified using univariate and multivariate analyses. Significant risk factors for PEP in the multivariate analysis were included in the final analysis to examine the synergistic effect of independent risk factors for PEP. Results: PEP occurred in 45 of 1,273 patients (3.5%). Three factors including difficult cannulation ≥10 minutes, pancreatic injection, and normal serum bilirubin level were included in the final analysis. The incidences of PEP in patients with zero, one, two, and three factors were 0.5% (2/388), 1.9% (9/465), 6.0% (17/285), and 12.6% (17/135), respectively. With increasing risk factors for PEP, the incidence of PEP significantly increased (1 factor vs. 2 factors, p=0.006; 2 factors vs. 3 factors, p=0.033). Conclusions: As the number of risk factors for PEP increases, the risk of PEP may not be additive; however, it may multiply. Thus, aggressive prophylaxis for PEP is strongly recommended in patients with multiple risk factors.

Risk factors for placenta accreta spectrum in pregnancies conceived after frozen-thawed embryo transfer in a hormone replacement cycle.

OBJECTIVE: Assisted reproductive technology (ART), especially frozen-thawed embryo transfer (FET) in a hormone replacement cycle (HRC), is a risk factor for placenta accreta spectrum (PAS). This study aimed to clarify the risk factors for PAS related to the maternal background and ART techniques in pregnancies achieved after FET in an HRC. STUDY DESIGN: We performed a case-control study in two tertiary perinatal centres in Japan. Among 14,028 patients who delivered at ≥24 weeks of gestation or were transferred after delivery to two tertiary perinatal centres between 2010 and 2021, 972 conceived with ART and 13,056 conceived without ART. PAS was diagnosed on the basis of the FIGO classification for the clinical diagnosis of PAS or retained products of conception after delivery at ≥24 weeks of gestation. We excluded women with fresh embryo transfer, FET with a spontaneous ovulatory cycle, a donor oocyte cycle, and missing details of the ART treatment. Finally, among women who conceived after FET in an HRC, 62 with PAS and 340 without PAS were included in this study. Multivariate logistic regression models were used for case-control comparisons, with adjustment for maternal age at delivery, parity, endometriosis or adenomyosis, the number of previous uterine surgeries of caesarean section, myomectomy, endometrial polypectomy or endometrial curettage, placenta previa, the stage of transferred embryos, and endometrial thickness at the initiation of progestin administration. RESULTS: PAS was associated with ≥2 previous uterine surgeries (adjusted odds ratio, 3.57; 95 % confidence interval, 1.60-7.97) and the stage of embryo transfer (blastocysts: adjusted odds ratio, 2.89; 95 % confidence interval, 1.15-7.26). In patients with <2 previous uterine surgeries, PAS was associated with an endometrial thickness of <7.0 mm (adjusted odds ratio, 5.18; 95 % confidence interval, 1.10-24.44). CONCLUSION: Multiple uterine surgeries and the transfer of blastocysts are risk factors for PAS in pregnancies conceived after FET in an HRC. In women with <2 previous uterine surgeries, a thin endometrium before FET is also a risk factor for PAS in these pregnancies.

Roles of Visiting Nurses in Supporting Medically Dependent Children Living at Home.

The purpose of this study was to identify the fundamental roles of visiting nurses as a foundation for creating effective educational programs for nurses of medically dependent (MD) children being treated at home. The relationship among the statements representing 3 types of roles was analyzed using structural equation modeling. There were 296 participants involved in performing home-visit nursing for MD children. Their structural roles related to home-visit nursing systems and skills were strongly correlated with the interpersonal roles related to support for MD children and their families, arrangements for whole families, and interprofessional collaborations. The correlations between these roles and the role determination process demonstrated that their future vision and selfgrowth were weak. This study makes the following recommendations: the development of specialized approaches to nursing practices; training in interprofessional collaboration; the realization of professional self-growth; and the creation of educational programs to assist visiting nurses in improving the home-visit nursing systems.

Development of a Prediction Model for Subjective Physical Symptoms Induced During Systematic Anatomy Practice Among Medical Students.

To prevent unpleasant symptoms in medical students during systematic anatomy practice, we aimed to develop and validate a model that predicts the likelihood of these symptoms occurring during practice based on risk factors prior to the start of practice. A total of 452 medical students enrolled from 2014 to 2018 were surveyed before and during practice, with questions regarding their sex, psychological status, subjective symptoms, and allergies. The sum of the scores concerning three subjective symptoms related to the eyes and three subjective symptoms related to the nose and fatigue were defined as the "eye-score" and "mask-score," respectively, and a total score of 7 or more was considered symptomatic. A prediction model was developed based on a generalized linear mixed model; the outcome variable in the model was symptoms during practice, and the explanatory variables were indoor formaldehyde concentration during practice, sex, and pre-practice status, such as the students' psychological state, eye-score, mask-score, and the presence of allergies. Five-fold cross-validation was used to assess internal validity and the prediction model was applied to 110 medical students enrolled in 2021 to assess external validity. The sensitivity and specificity by five-fold cross-validation were 0.843 and 0.314 for eye symptoms and 0.847 and 0.432 for mask symptoms. In the external validity assessment, the sensitivity and specificity were 0.889 and 0.207 for eye symptoms and 0.879 and 0.532 for mask symptoms. The prediction model developed in this study can be used in future measures aimed at preventing symptoms in students.

Comparison of Outcomes between a Basket Catheter and a Balloon Catheter for Endoscopic Common Bile Duct Stone Removal.

INTRODUCTION: Evidence for the outcomes of endoscopic retrograde cholangiopancreatography (ERCP) between a basket catheter and a balloon catheter for endoscopic common bile duct stone (CBDS) removal is lacking. This study aimed to compare ERCP outcomes using a basket catheter and a balloon catheter for endoscopic CBDS removal. METHODS: This multicenter retrospective study included 904 consecutive patients with native papilla who underwent endoscopic stone removal for CBDS ≤10 mm using a basket catheter and/or a balloon catheter at three institutions in Japan. ERCP outcomes between the basket and balloon groups were compared using inverse probability of treatment weighting (IPTW) method. RESULTS: ERCP-related adverse events occurred in 6.5% (29/449) and 7.7% (35/455) of patients in the basket and balloon groups, respectively (IPTW-adjusted p = 0.52). The incidences of post-ERCP pancreatitis, cholangitis, and perforation were similar in the basket and balloon groups (3.8% vs. 2.9%, 1.3% vs. 0.9%, and 0.7% vs. 0.7%, respectively). However, bleeding incidences were significantly higher in the balloon group than in the basket group (3.3% vs. 0.7%, IPTW-adjusted p = 0.012). Successful complete stone removal at one ERCP session using a single catheter was achieved in 17.8% (80/449) in the basket group and in 81.3% (370/455) in the balloon group (IPTW-adjusted p < 0.001). DISCUSSION: A balloon catheter is more likely to complete stone extraction for CBDS ≤10 mm with a single catheter at one endoscopic stone removal session. However, the risk for post-ERCP bleeding is higher in the balloon group than in the basket group.

Association between Non-Lipid Residual Risk Factors and Cardiovascular Events in Patients with Stable Coronary Artery Disease Treated with Pitavastatin: An Observation from the REAL-CAD Study.

AIMS: We aimed to investigate the association between non-lipid residual risk factors and cardiovascular events in patients with stable coronary artery disease (CAD) who achieved low-density lipoprotein cholesterol (LDL-C) ＜100 mg/dL from the Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) study. METHODS: The REAL-CAD study was a prospective, multicenter, open-label trial. As a sub-study, we examined the prognostic impact of non-lipid residual risk factors, including blood pressure, glucose level, and renal function, in patients who achieved LDL-C ＜100 mg/dL at 6 months after pitavastatin therapy. Each risk factor was classified according to severity. The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, and unstable angina requiring emergency hospitalization. RESULTS: Among 8,743 patients, the mean age was 68±8.2 years, and the mean LDL-C level was 84.4±18 mg/dL. After adjusting for the effects of confounders, an estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73 m2 showed the highest risk of the primary outcome (hazard ratio [HR] 1.92; 95% confidence interval [CI] 1.45-2.53). The combination of eGFR ≤ 60 and hemoglobin A1c (HbA1c) ≥ 6.0% also showed the highest risk of all-cause death (HR, 2.42; 95% CI, 1.72-3.41). CONCLUSIONS: In patients with stable CAD treated with pitavastatin and who achieved guidelines-directed levels of LDL-C, eGFR and HbA1c were independently associated with adverse events, suggesting that renal function and glycemic control could be residual non-lipid therapeutic targets after statin therapy.

Objective sleep was longitudinally associated with brain amyloid burden in mild cognitive impairment.

OBJECTIVE: Understanding the longitudinal association of objective sleep and physical activity with brain amyloid burden and cortical glucose metabolism has critical clinical and public health implications for dementia prevention in later life. METHODS: We enrolled 118 individuals aged ≥65 years with mild cognitive impairment, who were followed up on from August 2015 to September 2019. All participants continuously wore an accelerometer sensor for 7 consecutive days every 3 months and received annual 11 C-Pittsburgh compound-B and 18 F-fluorodeoxyglucose positron emission tomography (PET). Sleep and physical activity parameters were assessed using accelerometer sensor data and PET imaging was quantified using a standardized uptake-value ratio. Fifty-seven participants (48.3%) completed a lifestyle factor assessment and PET imaging over the 3-year period. A linear mixed-effects model was applied to examine the longitudinal association of sleep and physical activity parameters with PET imaging over the 3-year period, controlling for potential confounders. RESULTS: Sleep efficiency was inversely associated with amyloid uptake in the frontal lobe. Although sleep duration was positively associated with global amyloid uptake, particularly in the frontal lobe, their impact was extremely small. However, physical activity parameters were not significantly associated with the 11 C-Pittsburgh compound-B-uptake. Furthermore, sleep and physical activity parameters were not significantly associated with cortical glucose metabolism. INTERPRETATION: Lower sleep efficiency could be an early symptom of greater brain amyloid burden at the mild cognitive impairment stage. Therefore, the assessment of sleep may be useful for identifying individuals at higher risk for brain amyloid burden. Future longer term observational studies are required to confirm these findings.

Lifestyle factors that affect cognitive function-a longitudinal objective analysis.

Background: Identifying lifestyle factors associated with cognitive decline has critical clinical and public health implications for dementia prevention in later life. The longitudinal associations of sleep and physical activity with cognitive function remain unclear. This study examined whether objectively measured sleep and physical activity were longitudinally associated with cognitive function in older adults over a three-year period. Methods: This prospective cohort study enrolled 855 community-dwelling adults aged 65 and older, who were followed from 2015 to 2019. All participants were required to wear a wearable sensor for 7 consecutive days every 3 months and had annual cognitive assessments. Wearable sensor data (August 2015-September 2019) and Mini-Mental State Examination (MMSE) scores (August 2015-April 2019) were collected over 3 years of follow-up. First, principal component analysis was conducted to reduce the dimensions of the sleep and physical activity variables to two principal components for inclusion in a mixed-effects model. The sleep index consisted of sleep efficiency, time awake after sleep onset, and waking frequency. The physical activity index was composed of walking comprised steps per day and time devoted to light or moderate-to-vigorous physical activity. A higher sleep index indicated poor sleep quality, whereas a lower physical activity index indicated less physical activity. Second, a linear mixed effect model was used to examine the longitudinal association of sleep and physical activity indices with cognitive decline over time. Results: In total, 855 adults were recruited for this study at baseline. Of these, 729 adults (85.3%) completed a measurement of lifestyle factors and an annual cognitive testing, whereas 126 were excluded because of death or loss during follow-up. After adjusting for age, sex, education level, and time, the sleep index was inversely associated with MMSE scores (estimate, -0.06229; standard error, 0.02202; p = 0.0047) and the physical activity index was positively associated with MMSE scores (estimate, 0.06699; standard error, 0.03343; p = 0.0453). Conclusion: Poor sleep quality and lower physical activity were significant risk factors for subsequent cognitive decline in older adults. The present study facilitates the development of novel evidence-based interventions for physical activity and sleep quality to delay cognitive decline.

Combination of Prednisolone and Calcineurin Inhibitors Prevents Lung Function Decline in Patients with Anti-aminoacyl-tRNA Synthetase Antibody-Positive Polymyositis/Dermatomyositis.

OBJECTIVE: Anti-aminoacyl-tRNA synthetase antibody-positive polymyositis/dermatomyositis-associ ated interstitial lung disease (ARS-ILD) has a good prognosis, with few cases progressing to respiratory failure. This study aimed to determine factors predictive of lung function changes in patients with ARS-ILD. METHODS: We retrospectively studied 49 patients with ARS-ILD treated at Kurume University Hospital Hospital between 2000 and 2018. We followed 30 patients for more than 2 years after prednisolone (PSL) therapy, with or without calcineurin inhibitors (CNIs), evaluating clinical, physiological, computed tomography, pulmonary func tion, and serological data. RESULTS: After treatment for 24 months, no significant differences were noted between clinical parameters and improvement in forced vital capacity (FVC), %FVC, % carbon monoxide diffusing capacity/alveolar volume (%DLCO), and %DLCO/alveolar volume. Conversely, the annual change of %FVC significantly correlated with the Medical Research Council dyspnea scale grade and %FVC at the first visit and treatment. Furthermore, the annual change of %DLCO/VA significantly correlated with the duration from the first visit to treatment initiation. CONCLUSION: Compared with PSL monotherapy, combining PSL and CNI showed greater mitigation of %FVC decline. The time from onset of ARS-ILD to the first visit is critical for preventing a decline in lung function, and as such, patients should be monitored carefully.

Preoperative Chemotherapy Followed by Hepatectomy for Potentially Resectable UICC7 Stage IIIA, IIIB Hepatocellular Carcinoma; A Phase II Clinical Trial.

BACKGROUND: The Japanese guideline for therapeutic strategy in HCC does not recognize any benefit of preoperative chemotherapy for potentially resectable hepatocellular carcinoma (HCC), and only upfront resec tion is recommended even for an advanced HCC. Data on preoperative chemotherapy for advanced HCC is still limited. Poor prognostic factors of HCC after resection are tumor more than 5 cm in diameter, multiple lesions, and gross tumor thrombosis, which constitute UICC7 Stage IIIA and IIIB HCC. There are no prospective studies about preoperative chemotherapy in these patients. AIM: To evaluate the benefit of preoperative chemotherapy for UICC7 Stage IIIA and IIIB potentially resectable HCC. DISCUSSION: Our recent study demonstrated that the 5-year overall survival rate (OS) of patients diagnosed as UICC7 Stage IIIA and IIIB who had received upfront resection was only 16.5%. In contrast, the 5-year OS of UICC7 Stage IIIA and IIIB initially unresectable patients who had achieved conversion from unresectable to resect able status under successful hepatic infusion chemotherapy prior to resection was as high as 61.3%. Additionally, recent studies reported transarterial chemoembolization achieved outcomes comparable with those of resection. Therefore, we believe that patients with UICC7 Stage IIIA and IIIB should be considered borderline resectable. To evaluate this hypothesis we registered the present phase II clinical trial to assess the benefit of preoperative chemo therapy followed by hepatectomy in potentially resectable UICC7 Stage IIIA and IIIB HCC patients.

Residual Coronary Risk Factors Associated With Long-Term Clinical Outcomes in Patients With Coronary Artery Disease Treated With High- vs. Low-Dose Statin Therapy　- REAL-CAD Substudy.

BACKGROUND: It remains unclear which comorbidities, other than lipid parameters, or combination of comorbidities, best predicts cardiovascular events in patients with known coronary artery disease (CAD) treated with statins. Therefore, we aimed to identify the nonlipid-related prognostic factors and risk stratification of patients with stable CAD enrolled in the REAL-CAD study.Methods and Results: Blood pressure, glucose level, and renal function were considered as risk factors in the 11,141 enrolled patients. The primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, and unstable angina. The secondary composite endpoint was the primary endpoint and/or coronary revascularization. A significantly worse prognosis at the primary endpoint was observed in the estimated glomerular filtration rate (eGFR) ≤60 group, and the combination of eGFR ≤60 and HbA1c ≥6.0 was the worst (hazard ratio (HR) 1.66; P<0.001). However, even in the eGFR >60 group, systolic blood pressure (SBP) ≥140 mmHg met the secondary endpoint (HR 1.33; P=0.006), and the combination of eGFR ≤60 and HbA1c ≥6.0 was also the worst at the secondary endpoint (HR 1.35; P=0.002). CONCLUSIONS: Regarding nonlipid prognostic factors contributing to the incidence of cardiovascular events in statin-treated CAD patients, renal dysfunction was the most significant, followed by poor glucose control and high SBP.

Development of an Algorithm to Predict Recurrences After Resection of Liver Metastases in Patients With Metastatic Colorectal Cancer.

BACKGROUND/AIM: Hepatic recurrences after resection of metastatic lesions in advanced colorectal cancer (CRC) have an enormous impact on patient prognosis. Response evaluation criteria in solid tumor (RECIST) or morphologic response on computed tomography (CT) have been reported as surrogate prognostication markers. This study assessed a novel algorithm for the prognostication of liver metastasis treatment. PATIENTS AND METHODS: Forty-seven patients with liver metastases from CRC who underwent liver resection after systemic chemotherapy were included. The CT values examined before and after chemotherapy were collected. The velocity of CT values (CTvΔ) was calculated, and the subjects were divided into CTvΔ_high and _low groups. Clinicopathological variables, recurrence-free survival (RFS), and overall survival (OS) were statistically compared between the two groups. In addition, the effect of the combined evaluation of CTvΔ and carcinoembryonic antigen (CEA) was evaluated. RESULTS: In univariate analyses, the hazard ratio (HR) for a recurrence after liver resection was relatively higher in the RECIST_stable disease (SD) or _progressive disease (PD) and the CTvΔ_low groups. In multivariate analysis, the HR was significantly higher in the CEA_high, the RECIST_SD or PD, and the CTvΔ_low groups. The RFS was significantly longer in the CTvΔ_high group. Furthermore, the combination of CTvΔ and CEA predicted the RFS and OS. CONCLUSION: Our algorithm using CTvΔ could be a useful tool to select patients suitable for liver resection of hepatic CRC metastases.

Usefulness of a 4-Grade Novel Mouthpiece Device for Increased Mouth Pressure Reproducing Artificial Difficulty in Breathing.

OBJECTIVE: The use of a novel 4-grade mouthpiece device to reproduce difficulty in breathing was assessed in healthy individuals. METHODS: A double-blind, randomized, crossover-controlled trial was conducted to investigate the efficacy and safety of the device with increasing mouth pressure. The modified Borg (mBorg) scale values, respiratory system resistance at 5 Hz (R5), and forced expiratory volume in one second (FEV1) were assessed while using the device. MATERIALS: The four grades of breathing difficulty device were tested in 32 healthy participants. RESULTS: The 4-grade device linearly worsened the mBorg scale with increasing mouth pressure. The mean R5 (± standard deviation [SD]) with grade I, II, III, and IV devices were 5.6 ± 0.1, 10.3 ± 0.3, 21.5 ± 0.7, and 54.8 ± 2.0 kPa/L/s, respectively. The mean %FEV1 predicted (± SD) were 83.6 ± 15.9% with grade I, 55.3 ± 11.8% with grade II, 32.0 ± 6.1% with grade III, and 15.3 ± 3.2% with the grade IV device. The mBorg scale was positively correlated with R5 (r = 0.79, p < 0.0001) and negatively with %FEV1 predicted (r = -0.81, p < 0.0001). No severe adverse events were reported during the trial. CONCLUSION: We demonstrated that the novel device could effectively reproduce the semi-quantitative artificial difficulty in breathing safely and easily in healthy individuals. These devices could be helpful to understand the mechanisms of difficulty in breathing.

Weakened Grip Strength Over 40 Years in a Community-Dwelling Cohort in Tanushimaru, Japan.

BACKGROUND: An epidemiological survey has been periodically performed since 1977 among the adult population in Tanushimaru, a typical farming town in Japan. We aimed in this study to retrospectively investigate changes of grip strength (GS) and its correlates over 40 years in the same cohort of community-dwelling adults. We used pooled data from the survey to deduce essential correlates of GS in community-dwelling adults. METHODS: We retrospectively compared serial correlates of GS in the adult population in Tanushimaru between a population tested in 1977 and 1979 (Cohort A, n=2,452) and another population tested in 2016 and 2018 (Cohort B, n=1,505), to identify essential correlates of GS for investigating changes in GS during the past 40 years in community-dwelling adults. RESULTS: Age, height, weight, and the occupation of the subjects remained as correlates of GS in both genders during the past 40 years. In males, abdominal circumference also remained as a correlate of GS. Serum albumin levels in males and systolic blood pressure in females were identified as new correlates. GS after adjustment for the above correlates weakened in both genders, and the serial change in GS was particularly remarkable in subjects whose occupations were Class-1 and Class-2, which were defined as moderately hard work. CONCLUSIONS: From a periodically-performed epidemiological survey of a community-dwelling cohort in a Japanese typical farming town, age, height, weight, and occupation were deduced as essential correlates of GS. GS in the community dwelling cohort weakened in both genders over 40 years, possibly affected by their occupation.

Post-endoscopic Retrograde Cholangiopancreatography Pancreatitis after Conservative Treatment for Symptomatic Bile Duct Stones.

Introduction: Endoscopic retrograde cholangiopancreatography (ERCP) for asymptomatic common bile duct stones (CBDS) has been associated with an increased risk of post-ERCP pancreatitis (PEP). Patients with asymptomatic CBDS at the time of ERCP include those with incidentally discovered CBDS (group A) and previously symptomatic patients with CBDS who became asymptomatic after conservative treatment for symptomatic CBDS, including obstructive jaundice or acute cholangitis (group B). In this study, we aimed to examine PEP risk in group B by comparing PEP risks between groups A, B, and currently symptomatic patients (group C). Methods: In this multicenter retrospective study, we examined 77 patients in group A, 41 patients in group B, and 1225 patients in group C who had native papillae. PEP incidence rates between asymptomatic patients at the time of ERCP (groups A and B) and symptomatic patients (group C) were compared using one-to-one propensity score matching. Bonferroni's correction analysis was also performed to compare PEP incidence rates among the three groups. Results: As per our findings, PEP incidence rate in propensity score-matched groups A and B was significantly higher than that of propensity score-matched group C (13.2% [15/114] versus 4.4% [5/114], respectively, P = 0.033). In groups A and B, PEP incidence rates were 11.7% (9/77) and 14.6% (6/41), respectively. PEP risk in group B was similar to that in group A (P = 1.0). PEP incidence in group B was significantly higher than PEP incidence in group C (14.6% (6/41)) vs. 2.9% (35/1225)) (P = 0.005)). Conclusions: ERCP for previously symptomatic patients with CBDS who became asymptomatic after conservative treatment for symptomatic CBDS may increase the risk of PEP compared with ERCP for currently symptomatic patients. Thus, ERCP should be performed before patients become asymptomatic using conservative treatments if patients can tolerate ERCP procedures.

Correlation Between Work Motivation and Life Events in Female Physicians.

This study interviewed 39 mother-doctors from two university hospitals in Japan to investigate how certain stages in their lives influenced their working motivation. We conceptualized a Motivational Drive Chart to track changes of work motivation from enrollment in medical courses to the present day, recording changes in motivational values, age, and life events. It was found that the average value of motivation increased from the beginning of medical school enrollment until graduation; however, a sudden drop was noted in the age group 25 to 29 due to childcare and work-life conflicts. Motivational values were found to gradually increase in the 30 to 34 age group, owing to professional accomplishments, such as obtaining a specialist license. In Japanese society, social roles have traditionally been divided between men and women. The present study found that Japanese female doctors faced a decrease in work motivation during childrearing stages. The finding suggests that new avenues should be explored to support mother-doctors.

Characteristics of Immune Checkpoint Inhibitor-Induced Colitis: A Systematic Review.

BACKGROUND: Immune checkpoint inhibitors (ICIs) including anti-CTLA-4, anti-PD-1, and anti-PD-L1 antibodies have been increasingly used for various malignancies. These ICIs activate immune functions to treat malignant tumors; however, this causes characteristic complications called immune-related adverse events (irAE). In the gastrointestinal tract, ICIs cause adverse events such as diarrhea and enterocolitis, thus warranting treatment discontinuation. These irAEs require treatment that suppresses immunity; however, no treatment strategies based on approved guidelines have been reported. This review aimed to investigate the current treatment status for refractory cases of ICI-induced colitis in accordance with their diagnosis, therapy, and prognosis. SUMMARY: We systematically reviewed studies in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) checklist. Two investigators searched PubMed and Scopus in January 2019. We extracted data, including the number of ICI-treated patients developing colitis and diarrhea. The number of cases classified as severe per the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) definitions and the progress of corticosteroid-treated and anti-TNF-α- antibody-treated cases (e.g., infliximab) were recorded. Details of further treatment were also recorded for cases that did not improve with antiTNF-α- antibody. Among patients receiving anti-CTLA-4 antibody, corticosteroids were administered to 14.6% of patients, and infliximab was administered to 5.7% of patients. Among patients receiving anti-PD-1/PD-L1 antibody, corticosteroids were administered to 2.37% of patients. For refractory cases unsuccessful with infliximab, the continuation of infliximab every 2 weeks, tacrolimus administration, prolonged corticosteroid treatment, colectomy, or vedolizumab administration were reported. KEY MESSAGES: Treatment of ICI-induced colitis is important to avoid the need to discontinue cancer treatment. Many therapeutic agents for inflammatory bowel disease are reportedly effective in treating refractory ICI-induced colitis.