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Abstract Background In Japan, local governments have rural clinics designated for areas without physicians (RCDA) to secure physicians for rural medical care. Moreover, a medical policy of dispatching physicians between the RCDA and core hospitals for rural areas (CHRA) exists. This study aimed to assess the actual situation of physician migration from RCDAs and those who migrated, and examine the factors associated with their migration. Methods This retrospective cohort study used biennial national physicians’ survey data from 2012 to 2018. It targeted physicians who worked at RCDAs in 2012 and participated in all four surveys (n = 510). The physicians were divided into two groups. One group consisted of physicians who worked continuously at the RCDA over the four study periods (retained physicians, n = 278), and the other included physicians who migrated to other institutions midway through the study period (migrated physicians, n = 232). We tracked the types of facilities where RCDA physicians worked from 2012 to 2018, also examined the factors associated with their migration. Results Among physicians from RCDAs who migrated to other institutions (n = 151) between 2012 and 2014, many migrated to hospitals (n = 87/151, 57.6%), and some migrated to CHRA (n = 35/87, 40.2%). Physicians in their 40s (Hazard ratio 0.32 [95% CI 0.19–0.55]), 50s (0.20 [0.11–0.35]), and over 60 years (0.33 [0.20–0.56]) were more likely to remain at RCDAs. Changes in their area of practice (1.82 [1.34–2.45]) and an increase in the number of board certifications held by physicians between 2012 and 2018 (1.50 [1.09–2.06]) were associated with migration. Conclusions Many migrating physicians choose to work at hospitals after migrating from RCDAs. It was seemed that the physician dispatch system between RCDA and CHRA has been a measure to secure physicians in rural areas. Young age, obtaining board certification, and changes in areas of practice were associated with physician migration from RCDAs.

Background: A decrease in populations could affect healthcare access and systems, particularly in medically underserved areas (MUAs) where depopulation is becoming more prevalent. This study aimed to simulate the future population and land areas of MUAs in Japan. Methods: This study covered 380,948 1 km meshes, 87,942 clinics, and 8354 hospitals throughout Japan as of 2020. The areas outside a 4 km radius of medical institutions were considered as MUAs, based on the measure of areas in the current Japanese Medical Care Act. Based on the population estimate for a 1 km mesh, the population of mesh numbers of MUAs was predicted for every 10 years from 2020 to 2050 using geographic information system analysis. If the population within a 4 km radius from a medical institution fell below 1000, the institution was operationally assumed to be closed. Results: The number of MUAs was predicted to decrease from 964,310 (0.77% of the total Japanese population) in 2020 to 763,410 (0.75%) by 2050. By 2050, 48,105 meshes (13% of the total meshes in Japan) were predicted to be new MUAs, indicating a 31% increase in MUAs from 2020 to 2050. By 2050, 1601 medical institutions were tentatively estimated to be in close proximity. Conclusions: In Japan, the population of MUAs will decrease, while the land area of MUAs will increase. Such changes may reform rural healthcare policy and systems.

Background: The number of clinics offering telemedicine in Japan has been increasing. Regional characteristics such as population density and the number of physicians may be associated with the provision of telemedicine. This study investigated the relationship between clinics offering telemedicine and such regional characteristics for each prefecture in Japan. Methods: Data were collected from publicly available information that included the percentage of clinics offering telemedicine (real-time synchronous type) among all clinics (in 2022), population density, and the number of physicians for each of Japan's 47 prefectures. An ecological study was carried out to determine the correlation between the percentage of clinics offering telemedicine and regional characteristics for each prefecture, and Pearson correlation analysis and multiple regression analysis adjusted for regional characteristics were performed. Results: The min?max and mean levels were, respectively, 3.4?39.2% and 15.6% of clinics offering telemedicine, 66.6?6402.6 and 657.1 people per square kilometer of population density, and 185.2?356.7 and 274.0 physicians per 100,000 people. Geographically, the northeastern regions appeared to show a high percentage of clinics offering telemedicine relative to the southwestern regions. There was a significant negative correlation between the percentage of clinics offering telemedicine and population density (r?=??0.31, p?0.05; ??=??0.31, p?

ObjectiveThis study aimed to identify the amount of weight loss needed in patients with obesity to improve metabolic syndrome (MetS), a risk factor for cardiovascular disease (CVD), over a long period of time.MethodsA total of 576 patients with obesity were enrolled in this study. Effects of continuous physician-supervised weight loss on the cumulative MetS components excluding abdominal circumference (defined as obesity-related CVD risk score) were investigated during a 5-year follow-up period. The extent of weight loss required to reduce the obesity-related CVD risk components was assessed using receiver operating characteristic (ROC) curve analyses.ResultsOf the 576 participants, 266 completed 5-year follow-up, with 39.1% and 24.1% of them achieving ≥5.0% and ≥7.5% weight loss at the 5-year follow-up, respectively. The area under the ROC curve for reducing the obesity-related CVD risk components was 0.719 [0.662–0.777] at 1 year and 0.694 [0.613–0.775] at 5 years. The optimal cut-off value for weight loss was 5.0% (0.66 sensitivity and 0.69 specificity) and the value with 0.80 specificity was 7.5% (0.45 sensitivity) at 5 years. Greater reductions in weight were associated with greater improvements in the obesity-related CVD risk score at all follow-up periods (P-trend

Metabolically Healthy Obesity (MHO) is generally recognized as the absence of any metabolic disorders and cardiovascular diseases, including type 2 diabetes, dyslipidemia, and hypertension, in obese individuals; however, it is not clearly defined. Therefore, the present study investigated differences in metabolic characteristics between individuals with MHO and Metabolically Unhealthy Obesity (MUO) during weight reduction therapy. The key factors defining MHO and the importance of weight reduction therapy for MHO were also examined. Cohort data from the Japan Obesity and Metabolic Syndrome (JOMS) study were analyzed. Subjects were divided into the MHO (n = 25) and MUO (n = 120) groups. Prior to weight reduction therapy, serum adiponectin levels were significantly higher in the MHO group than in the MUO group. Serum adiponectin levels also negatively correlated with the area of subcutaneous adipose tissue (SAT) and Homeostasis model assessment (HOMA)-R in the MHO group, but not in the MUO group. Collectively, the present results suggest the importance of adiponectin for maintaining metabolic homeostasis in the MHO group. On the other hand, no significant differences were observed in inflammatory markers between the MHO and MUO groups, suggesting the presence of chronic inflammation in both groups. Furthermore, a positive correlation was noted between changes in serum cystatin C levels and waist circumference in the MHO group, which indicated that despite the absence of metabolic disorders, the MHO group exhibited anti-inflammatory responses during weight reduction therapy. These results underscore the significance of weight reduction even for individuals with MHO.

Abstract Background Physician shortage and maldistribution is an urgent health policy issue requiring resolution. Determination of factors associated with regional retention and development of effective policy interventions will help to solve this issue. The purpose of the present study was to identify factors associated with regional retention and discuss their policy implications. Methods We conducted a cross-sectional online survey from February to March of 2022 for graduates from regional quotas (special quotas for medical schools to select students engaged in community medicine) and Jichi Medical University (JMU) and students at 10 medical schools including JMU. Completed surveys were obtained from 375 graduates and 1153 students. Questions included intention to continue to work in their home prefecture in the future, as well as background information and potential factors associated with regional retention. In the analyses, regional quotas and JMU were referred to as community medicine-oriented programs and schools (CMPS). We performed logistic regression analyses to identify factors associated with regional retention. Results Among the students, scholarship-bonded obligatory service, satisfaction with current life, intention to belong to ikyoku (a traditional physician allocation/training system in Japanese medical schools), and interest in general practice/family medicine were significantly positively associated with regional retention. Among the graduates, satisfaction with training environment, intention to belong to ikyoku, and recommending their program to high school students were significantly positively associated with regional retention. For students of CMPS, satisfaction with the career development program was positively associated with future regional retention. For graduates, this association was observed only in the crude analysis. Conclusions In addition to known factors such as interest in general practice/family medicine, intention to belong to ikyoku had a substantial impact on regional retention. The present results suggest that the career support system represented by ikyoku as well as a career development program are of potential importance for increasing regional retention through the mechanisms of a sense of belonging and a life-long education system. These findings provide useful information for the development of further policy interventions that interweave traditional and new systems to maximize their effectiveness.

BACKGROUND. Oxidized apolipoprotein B (oxLDL) and oxidized ApoA-I (oxHDL) are proatherogenic. Their prognostic value for assessing high-risk plaques by coronary computed tomography angiography (CCTA) is missing.METHODS. In a prospective, observational study, 306 participants with cardiovascular disease (CVD) had extensive lipoprotein profiling. Proteomics analysis was performed on isolated oxHDL, and atherosclerotic plaque assessment was accomplished by quantitative CCTA.RESULTS. Patients were predominantly White, overweight men (58.5%) on statin therapy (43.5%). Increase in LDL-C, ApoB, small dense LDL-C (P < 0.001 for all), triglycerides (P = 0.03), and lower HDL function were observed in the high oxLDL group. High oxLDL associated with necrotic burden (NB; β = 0.20; P < 0.0001) and fibrofatty burden (FFB; β = 0.15; P = 0.001) after multivariate adjustment. Low oxHDL had a significant reverse association with these plaque characteristics. Plasma oxHDL levels better predicted NB and FFB after adjustment (OR, 2.22; 95% CI, 1.27–3.88, and OR, 2.80; 95% CI, 1.71–4.58) compared with oxLDL and HDL-C. Interestingly, oxHDL associated with fibrous burden (FB) change over 3.3 years (β = 0.535; P = 0.033) when compared with oxLDL. Combined Met136 mono-oxidation and Trp132 dioxidation of HDL showed evident association with coronary artery calcium score (r = 0.786; P < 0.001) and FB (r = 0.539; P = 0.012) in high oxHDL, whereas Met136 mono-oxidation significantly associated with vulnerable plaque in low oxHDL.CONCLUSION. Our findings suggest that the investigated oxidized lipids are associated with high-risk coronary plaque features and progression over time in patients with CVD.TRIAL REGISTRATION. ClinicalTrials.gov NCT01621594.FUNDING. National Heart, Lung, and Blood Institute at the NIH Intramural Research Program.

BACKGROUND Cellular cholesterol efflux capacity (CEC) is a better predictor of cardiovascular disease (CVD) events than HDL-cholesterol (HDL-C) but is not suitable as a routine clinical assay.METHODS We developed an HDL-specific phospholipid efflux (HDL-SPE) assay to assess HDL functionality based on whole plasma HDL apolipoprotein–mediated solubilization of fluorescent phosphatidylethanolamine from artificial lipid donor particles. We first assessed the association of HDL-SPE with prevalent coronary artery disease (CAD): study I included NIH severe-CAD (n = 50) and non-CAD (n = 50) participants, who were frequency matched for sex, BMI, type 2 diabetes mellitus, and smoking; study II included Japanese CAD (n = 70) and non-CAD (n = 154) participants. We also examined the association of HDL-SPE with incident CVD events in the Prevention of Renal and Vascular End-stage Disease (PREVEND) study comparing 340 patients with 340 controls individually matched for age, sex, smoking, and HDL-C levels.RESULTS Receiver operating characteristic curves revealed stronger associations of HDL-SPE with prevalent CAD. The AUCs in study I were as follows: HDL-SPE, 0.68; apolipoprotein A-I (apoA-I), 0.62; HDL-C, 0.63; and CEC, 0.52. The AUCs in study II were as follows: HDL-SPE, 0.83; apoA-I, 0.64; and HDL-C, 0.53. Also longitudinally, HDL-SPE was significantly associated with incident CVD events independent of traditional risk factors with ORs below 0.2 per SD increment in the PREVEND study (P < 0.001).CONCLUSION HDL-SPE could serve as a routine clinical assay for improving CVD risk assessment and drug discovery.TRIAL REGISTRATION ClinicalTrials.gov NCT01621594.FUNDING NHLBI Intramural Research Program, NIH (HL006095-06).

Abstract Background Although many clinical parameters have been identified as predictors for cardiovascular disease (CVD) development in the general population, the accurate predictor for CVD in patients with obesity is still unknown. Objective The study aimed to explore an additional risk factor and predictor for CVD in patients with overweight/obesity considering the interaction of obesity‐related pathophysiology. Methods The Japan Obesity and Metabolic Syndrome study, a multicenter prospective study, enrolled 787 outpatients, of which 318 eligible patients were analyzed. Patients with fasting plasma glucose (FPG) levels ≥6.11 and

Abstract Calciprotein particles (CPPs) are colloids composed of solid-phase calcium-phosphate and serum protein fetuin-A. CPPs form a polydispersed system with different particle size and density. CPPs with specific physical properties can induce calcification and innate immune responses in cultured cells. In hemodialysis patients, blood CPP levels were reported to correlate with vascular calcification and inflammation. However, little is known about relation between these disorders and physical properties of CPPs. Here, we show that the association between physical properties of plasma CPPs and serum levels of inflammatory cytokines/chemokines in 78 hemodialysis out-patients by cross-sectional study. Patients with cardiovascular disease (CVD) had significantly higher high density CPP (H-CPP) levels than patients without CVD but not low density CPP (L-CPP). Seven cytokines/chemokines (EGF, eotaxin, IL-8, IP-10, MCP-1, MIP-1, MIP-1β and TNFα) were detectable in the serum samples from > 95% of the patients. In multivariate regression analysis, H-CPP was positively associated with eotaxin after adjusting for age, gender, smoking, serum phosphate and FGF23. L-CPP was negatively associated with IL-8 after adjusting for age, gender, serum albumin, phosphate and FGF23. High H-CPP levels were associated with pro-inflammatory response, whereas L-CPPs were associated with anti-inflammatory response. CPPs with different physical properties may impact differently on pathophysiology in HD patients.

Background: Difficulties experienced by mothers in raising their children can be resolved using social networking services (SNSs). Being aware of issues associated with SNSs in such situations may be useful for supporting mothers. We herein review the issues associated with using SNSs to support mothers. Methods: This review was conducted using an electronic search engine to search for articles that described issues associated with using SNSs to support mothers, and which were published up to August 2022. Results: After screening, a total of 19 articles were included. We thematically categorized the contents into three major issues associated with using SNSs for support of mothers: (1) issues on the management side, (2) issues on the user side, and (3) social and environmental issues. The mainly discussed issues were the safety of using SNSs and/or securing and training human resources on the management side, busyness of mothers on the user side, as well as sociocultural and communication environment-related limitations as social and environmental issues. Conclusions: The issues we detected would aid in developing the use of SNSs as a tool to support mothers. Further research on these issues is needed.

Abstract Weight reduction therapy represents a fundamental strategy to prevent nonalcoholic fatty liver disease (NAFLD) in patients with obesity, which may result in liver fibrosis. Histological findings previously demonstrated that weight reduction therapy attenuated NAFLD. The FIB4 index is widely used to assess the status of NAFLD. The present study investigated whether the FIB4 index improved during weight reduction therapy. We used cohort data of the Japan Obesity and Metabolic syndrome Study and examined the correlation between body weight (BW) loss (BW loss) and changes in the FIB4 index (ΔFIB4 index) in patients who successfully reduced their BW by more than 5% from baseline BW after 3, 6, and 12 months (M) of weight reduction therapy. A negative correlation (r = −0.342, p = 0.029) was observed between BW loss and FIB4 index after 3 M, but not after 6 M, whereas a positive correlation (r = 0.298, p = 0.03) was noted after 12 M. These results revealed changes in the correlation between ΔBW loss and ΔFIB4 index during the therapy, mainly due to time-dependent changes in components of the FIB4 index formula. Thus, we concluded that the FIB4 index is useful and reliable to assess liver fibrosis until 3 M during weight reduction therapy. However, after 3 M, we should recognize that the FIB4 index may not reflect liver status. Therefore, it is important to consider this characteristic of the FIB4 index as a limitation when assessing liver fibrosis in obese patients receiving weight reduction therapy.

Objective Predictors of prognosis are necessary for use in routine clinical practice for older patients with pneumonia, given the ageing of the population. Recently, the National Early Warning Score (NEWS), a comprehensive predictor of severity that consists solely of physiological indicators, has been proposed to predict the prognosis of pneumonia. The neutrophil/lymphocyte ratio (NLR) is a simple index of inflammation that may also be predictive of pneumonia. In the present study, we aimed to determine whether NEWS or a combination of NEWS and NLR predicts mortality in older patients with pneumonia.Design A retrospective cohort study.Setting A general hospital in Japan.Participants We collected data from patients aged ≥65 years with pneumonia who were admitted between 2018 and 2020 (n=282; age=85.3 (7.9)). Data regarding vital signs, demographics and the length of hospital stay, in addition to the NEWS and NLR, were extracted from the participants’ electronic medical records.Intervention The utility of the combination of NEWS and NLR was assessed using NEWS×NLR and NEWS+NLR.Main outcome measures Their predictive ability for 30-day mortality as the primary outcome was assessed using receiver operating characteristic (ROC) curve analysis.Results According to the NEWS classification, 80 (28.3%), 64 (22.7%) and 138 (48.9%) of the participants were at low, medium and high risk of mortality, respectively. The 30-day mortality for the entire cohort was 9.2% (n=26), and the mortality rate increased with the NEWS classification: low, 1.3%; medium, 7.8%; and high, 14.5%. The NLRs were 6.0 (4.2–9.8), 6.8 (4.8–10.4) and 14.6 (9.4–22.2), respectively (p

Nephrotic syndrome and hypothyroidism are respectively reported to influence renal hemodynamics and hypercholesterolemia. However, the relationship of proteinuria-associated thyroid function with renal hemodynamics and cholesterol metabolism has yet to be determined in a simultaneous analysis of thyroid, renal, and cholesterol variables. We investigated the hypothesis that the changes in thyroid hormones by proteinuria may contribute to changes in cholesterol metabolism and renal hemodynamics by proteinuria. Twenty-nine patients (17 men and 12 women) with proteinuric kidney disease (mean age 46 years) were enrolled in a pilot study. Data for serum free triiodothyronine (FT3), free thyroxine (FT4), total cholesterol, and filtration fraction (FF; assessed by para-aminohippuric acid clearance) were used in variable-adjusted correlation analyses. The patients had the following data (mean ± standard deviation): urinary protein 5.18 ± 3.28 g/day, FT3 2.18 ± 0.44 pg/mL, FT4 1.03 ± 0.26 ng/dL, FF 0.27 ± 0.07, and total cholesterol 327 ± 127 mg/dL. There was a significant positive correlation of FT3 with FF (β = 0.58, p = 0.01) and a significant inverse correlation of FT4 with total cholesterol (β = −0.40, p = 0.01). A positive correlation of FT3 with FF and an inverse correlation of FT4 with total cholesterol were demonstrated in patients with proteinuric kidney disease. The proteinuria-associated reduction in serum thyroid hormone levels was correlated with hypercholesterolemia and the reduced glomerular FF. Further studies of these relationships are required.

Introduction: Previous studies indicate that professional identity formation (PIF), the formation of a self-identity with the internalised values and norms of professionalism, may influence self-regulated learning (SRL). However, it remains unclear whether a PIF-oriented intervention can improve SRL in clinical education. The aim of this study was to explore whether a PIF-oriented mentoring platform improves SRL in a clinical clerkship. Methods: A mixed-methods study was conducted. Forty-one students in a community-based clinical clerkship (CBCC) used a PIF-oriented mentoring platform. They articulated the values and norms of professionalism in a professional identity essay, elaborated on future professional self-image, and reflected on their current compared to future selves. They made a study plan while referring to PIF-based self-reflection and completed it. The control group of 41 students completed CBCC without the PIF-oriented mentoring platform. Changes in SRL between the two groups were quantitatively compared using the Motivated Strategies for Learning Questionnaire. We explore how PIF elements in the platform affected SRL by qualitative analysis of questionnaire and interview data. Results: A moderate improvement in intrinsic goal orientation (p = 0.005, ε2 = 0.096) and a mild improvement in critical thinking (p = 0.041, ε2 = 0.051) were observed in the PIF-oriented platform group. Qualitative analysis revealed that the PIF-oriented platform fostered professional responsibility as a key to expanding learning goals. Gaining authentic knowledge professionally fostered critical thinking, and students began to elaborate knowledge in line with professional task processes. Conclusion: A PIF-oriented mentoring platform helped students improve SRL during a clinical clerkship.

Abstract Aims Endothelial cell vascular endothelial growth factor receptor 2 (VEGFR‐2) plays a pivotal role in angiogenesis, which induces physiological cardiomyocyte hypertrophy via paracrine signalling between endothelial cells and cardiomyocytes. We investigated whether a decrease in circulating soluble VEGFR‐2 (sVEGFR‐2) levels is associated with poor prognosis in patients with chronic heart failure (HF). Methods and results We performed a multicentre prospective cohort study of 1024 consecutive patients with HF, who were admitted to hospitals due to acute decompensated HF and were stabilized after initial management. Serum levels of sVEGFR‐2 were measured at discharge. Patients were followed up over 2 years. The outcomes were cardiovascular death, all‐cause death, major adverse cardiovascular events (MACE) defined as a composite of cardiovascular death and HF hospitalization, and HF hospitalization. The mean age of the patients was 75.5 (standard deviation, 12.6) years, and 57% were male. Patients with lower sVEGFR‐2 levels were older and more likely to be female, and had greater proportions of atrial fibrillation and anaemia, and lower proportions of diabetes, dyslipidaemia, and HF with reduced ejection fraction (

Abstract Background Recently, presepsin has been reported to be a useful biomarker for early diagnosis of sepsis and evaluation of prognosis in septic patients. However, few reports have evaluated its usefulness in patients with urinary tract infections (UTI). This study aimed to evaluate whether presepsin could be a valuable marker for detecting severe sepsis, and whether it could predict the therapeutic course in patients with UTI compared with markers already used: procalcitonin (PCT) and C-reactive protein (CRP). Methods From April 2014 to December 2016, a total of 50 patients with urinary tract infections admitted to Gunma university hospital were enrolled in this study. Vital signs, presepsin, PCT, CRP, white blood cell (WBC) count, causative agents of urinary-tract infections, and other data were evaluated on the enrollment, third, and fifth days. The patients were divided into two groups: with (n = 11) or without (n = 39) septic shock on the enrollment day, and with (n = 7) or without (n = 43) sepsis on the fifth day, respectively. Presepsin was evaluated as a biomarker for systemic inflammatory response syndrome (SIRS) or septic shock. Results Regarding the enrollment day, there was no significant difference of presepsin between the SIRS and non-SIRS groups (p = 0.276). The median value of presepsin (pg/mL) was significantly higher in the septic shock group (p

Abstract Background Japan has established comprehensive education-scholarship programs to supply physicians in rural areas. Their entrants now comprise 16% of all medical students, and graduates must work in rural areas for a designated number of years. These programs are now being adopted outside Japan, but their medium-term outcomes and inter-program differences are unknown. Methods A nationwide prospective cohort study of newly licensed physicians 2014–2018 (n = 2454) of the four major types of the programs—Jichi Medical University (Jichi); regional quota with scholarship; non-quota with scholarship (scholarship alone); and quota without scholarship (quota alone)—and all Japanese physicians in the same postgraduate year (n = 40,293) was conducted with follow-up workplace information from the Physician Census 2018, Ministry of Health, Labour and Welfare. In addition, annual cross-sectional survey for prefectural governments and medical schools 2014–2019 was conducted to obtain information on the results of National Physician License Examination and retention status for contractual workforce. Results Passing rate of the National Physician License Examination was highest in Jichi, followed in descending order by quota with scholarship, the other two programs, and all medical graduates. The retention rate for contractual rural service of Jichi graduates 5 years after graduation (n = 683; 98%) was higher than that of quota with scholarship (2868; 90%; P

Abstract Background High-dose intravenous immunoglobulin (IVIG) is the mainstay of treatment for Kawasaki disease (KD). Usually, 2 g/kg of IVIG is administered over 10–24 h, depending on the institution or physician, but the association between infusion speed and effectiveness has not been reported. In this study, we evaluated the differences in efficacy and safety between two different IVIG administration speeds. Methods This was a multicenter, unblinded, randomized controlled study. Patients newly diagnosed with KD were randomized into two groups: one who received IVIG over 12 h (12H group, double speed), and one that received IVIG over 24 h (24H group, reference speed). The endpoints included the duration of fever, incidence of coronary artery abnormalities (CAAs) and of adverse events. Laboratory data were evaluated before and after IVIG administration. Results A total of 39 patients were enrolled. There was no difference between groups in fever duration after the initiation of IVIG (21 h vs. 21.5 h, p = 0.325), and no patient experienced CAAs. Two adverse events were observed in the 12H group (elevation of aspartate aminotransferase and vomiting), however no severe adverse events requiring treatments or extension of hospital stay were observed in either group. After initial IVIG administration, the change ratio of inflammatory markers, such as white blood cell counts, neutrophils, C-reactive protein, and albumin, did not show significant differences between the two groups. On the other hand, a greater increase of serum immunoglobulin G from its baseline level was observed in the 24H group compared to the 12H group (3037 ± 648 mg/dl vs. 2414 ± 248 mg/dl, p

Abstract Background Primary care physicians have diverse responsibilities. To collaborate with cancer specialists efficiently, they should prioritise roles desired by other collaborators rather than roles based on their own beliefs. No previous studies have reported the priority of roles such clinic-based general practitioners are expected to fulfil across the cancer care continuum. This study clarified the desired roles of clinic-based general practitioners to maximise person-centred cancer care. Methods A web-based multicentre questionnaire in Japan was distributed to physicians in 2019. Physician roles within the cancer care continuum were divided into 12 categories, including prevention, diagnosis, surgery, follow-up with cancer survivors, chemotherapy, and palliative care. Responses were evaluated by the proportion of three high-priority items to determine the expected roles of clinic-based general practitioners according to responding physicians in similarly designated roles. Results Seventy-eight departments (25% of those recruited) from 49 institutions returned questionnaires. Results revealed that some physicians had lower expectations for clinic-based general practitioners to diagnose cancer, and instead expected them to provide palliative care. However, some physicians expected clinic-based general practitioners to be involved in some treatment and survivorship care, though the clinic-based general practitioners did not report the same priority. Conclusion Clinic-based general practitioners prioritised involvement in prevention, diagnoses, and palliative care across the cancer continuum, although lower expectations were placed on them than they thought. Some additional expectations of their involvement in cancer treatment and survivorship care were unanticipated by them. These gaps represent issues that should be addressed.

Abstract Background Cervical lymphadenopathy is commonly seen in general practice, and its etiology is diverse. Establishing the diagnostic strategy for lymphadenopathy would be desirable to avoid overlooking neoplasms or other critical conditions. This study aims to identify the useful laboratory parameters for cervical lymphadenopathy that require clinical observation or intervention. Methods The participants were outpatients presenting cervical swelling or cervical lymph node (LN) pain who consulted the General Internal Medicine department from 2010 to 2016. We evaluated the characteristics, physical findings, and laboratory parameters with final diagnoses by multivariate logistic regression analysis. We categorized the final diagnoses as “Clinical Intervention Required Group (CIRG)” including necrotizing lymphadenitis, hematologic neoplasms, metastatic lymphadenopathy, tuberculous lymphadenitis, bacterial infectious diseases, infectious mononucleosis, autoimmune diseases, and other abnormal conditions or “No‐CIRG” not requiring further clinical observation or intervention. Results We evaluated 409 participants, with 130 (31.8%) diagnosed as belonging to the CIRG. There was an association between CIRG and various parameters: age ≥60 years old (adjusted odds ratio [AOR], 2.70; 95% confidence interval [CI], 1.48‐4.90), having a referral (AOR, 1.83; 95% CI, 1.12‐3.00), diameter of LN ≥ 2 cm (AOR, 1.91; 95% CI, 1.05‐3.48), fixed LNs (AOR, 2.74; 95% CI, 1.02‐7.37), and lactate dehydrogenase (LD) ≥400 U/L (AOR, 3.78; 95% CI, 1.46‐9.77). Eighty‐two percent of LD ≥ 400 cases in the CIRG were infectious mononucleosis or necrotizing lymphadenitis. Conclusions Besides the clinical indicators reported previously, we may apply an elevated LD level as a useful indicator of cervical lymphadenopathy that requires further clinical observation or intervention.

Introduction Helicobacter pylori (H. pylori) is a bacterium that causes chronic gastroduodenal infection and affects various systemic diseases. An increase in the blood level of C-reactive protein (CRP; a systemic inflammatory marker), at a low-grade chronic inflammation level, is observed in cases of infection. However, the effect of H. pylori eradication on CRP remains undetermined. Therefore, we aimed to see the circulating CRP levels in eradicated patients through a meta-analysis. Material and methods The PubMed database was searched from its inception to June 2020. Studies that described the CRP levels following H. pylori eradication were collected. A random-effects meta-analysis was then performed using an inverse variance with standardized mean difference. Results A total of 10 eligible studies (642 subjects in total) were available. The median age in the studies was 49.9 years old. The CRP level was 6.0 (median) mg/L before H. pylori eradication and 5.8 (median) mg/L after eradication. From the results of overall meta-analysis, there was found to be a significant reduction in the CRP levels with H. pylori eradication (standardized mean difference: -0.64; 95% confidence interval: -1.02 to -0.27). The result was not similarly confirmed in a subanalysis of the available randomized controlled trials. Conclusions Weak evidence exists in terms of the effects of H. pylori eradication on the reduced CRP levels. Further research is called for.

ObjectiveType 2 diabetes is a risk factor for dementia. We investigated whether serum levels of soluble triggering receptor expressed on myeloid cell 2 (sTREM2), a soluble form of the cell surface receptor TREM2, were predictive of cognitive impairment in type 2 diabetes without obesity.MethodsA total of 166 Japanese patients with type 2 diabetes without obesity were followed-up for 2 years. We measured clinical parameters, assessed cognitive function using the mini-mental state examination (MMSE), quantified and divided serum sTREM2 levels into quartiles, and examined the longitudinal associations.ResultsDuring the follow-up, HbA1c levels were elevated in 98 patients and decreased in 68 patients. In the HbA1c-elevated group, higher sTREM2 levels at baseline showed a significant association with a greater tendency for reduction in MMSE scores (P for trend = 0.015), whereas they were not significantly associated with other examined parameters. In the HbA1c-decreased group, there was no significant association between sTREM2 levels at baseline and changes in MMSE scores, but higher sTREM2 levels at baseline were significantly associated with a greater tendency for reduction in waist circumference (P for trend = 0.027), homeostasis model assessment of insulin resistance (P for trend = 0.039), and sTREM2 levels (P for trend = 0.023).ConclusionsGlycemic control is suggested to be important in preventing cognitive impairment in patients with type 2 diabetes without obesity. Higher serum sTREM2 levels would be a predictive marker for cognitive impairment in inadequately controlled type 2 diabetes without obesity.

Abstract Objectives Frequent self-weighing is associated with weight loss and maintenance, but the relationship between frequent self-weighing and the incidence of type 2 diabetes (T2D) remains unclear. The study aim was to examine the association between self-weighing frequency and the incidence of T2D in people with impaired fasting glucose (IFG). Results We tested the hypothesis that self-weighing frequency and the incidence of T2D are associated in 2607 people with IFG (1240 in the intervention arm; 1367 in the self-directed control arm). Both arms received a weighing scale with storage function. Healthcare providers offered a one-year goal-focused lifestyle intervention via phone. Participants were divided into 4 categories based on self-weighing frequency (No data sent [reference group], low:

Abstract Background Following community clinical placements, medical students use reflective writing to discover the story of their journey to becoming medical professionals. However, because of assessor bias analyzing these writings qualitatively to generalize learner experiences may be problematic. This study uses a process-oriented text mining approach to better understand meanings of learner experiences by connecting key concepts in extended student reflective essays. Methods Text mining quantitative analysis is used on self-evaluative essays (n = 47, unique word count range 43–575) by fifth-year students at a regional quota-system university in Japan that specializes in training general practitioners for underserved communities. First, six highly-occurring key words were identified: patient, systemic treatment, locale, hospital, care, and training. Then, standardized keyword frequency analysis robust to overall essay length and keyword volume used individual keywords as “nodes” to calculate per-keyword values for each essay. Finally, Principle Components Analysis and regression were used to analyze key word relationships. Results Component loadings were strongest for the keyword area, indicating most shared variance. Multiply regressing three of the remaining keywords hospital, systemic treatment, and training yielded R2 = 0.45, considered high for this exploratory study. In contrast, direct patient experience for students was difficult to generalize. Conclusions Impressions of the practicing area environment were strongest in students, and these impressions were influenced by hospital workplace, treatment provision, and training. Text mining can extract information from larger samples of student essays in an efficient and objective manner, as well as identify patterns between learning situations to create models of the learning experience. Possible implications for community-based clinical learning may be greater understanding of student experiences for on-site precepts benefitting their roles as mentors.

Background The impact of chronic kidney disease (CKD) on the prognostic utility of cardiovascular biomarkers in high‐risk patients remains unclear. Methods and Results We performed a multicenter, prospective cohort study of 3255 patients with suspected or known coronary artery disease (CAD) to investigate whether CKD modifies the prognostic utility of cardiovascular biomarkers. Serum levels of cardiovascular and renal biomarkers, including soluble fms‐like tyrosine kinase‐1 (sFlt‐1), N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), high‐sensitivity cardiac troponin‐I (hs‐cTnI), cystatin C, and placental growth factor, were measured in 1301 CKD and 1954 patients without CKD. The urine albumin to creatinine ratio (UACR) was measured in patients with CKD. The primary outcome was 3‐point MACE (3P‐MACE) defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. The secondary outcomes were all‐cause death, cardiovascular death, and 5P‐MACE defined as a composite of 3P‐MACE, heart failure hospitalization, and coronary/peripheral artery revascularization. After adjustment for clinical confounders, sFlt‐1, NT‐proBNP, and hs‐cTnI, but not other biomarkers, were significantly associated with 3P‐MACE, all‐cause death, and cardiovascular death in the entire cohort and in patients without CKD. These associations were still significant in CKD only for NT‐proBNP and hs‐cTnI. NT‐proBNP and hs‐cTnI were also significantly associated with 5P‐MACE in CKD. The UACR was not significantly associated with any outcomes in CKD. NT‐proBNP and hs‐cTnI added incremental prognostic information for all outcomes to the model with potential clinical confounders in CKD. Conclusions NT‐proBNP and hs‐cTnI were the most powerful prognostic biomarkers in patients with suspected or known CAD and concomitant CKD.

BackgroundThe oxidized high-density lipoprotein (oxHDL) is a possible marker for cardiovascular diseases. This study investigated the effects of smoking cessation with varenicline (a partial agonist of nicotinic acetylcholine receptors) on the levels of oxHDL in the serum of subjects compared with those of high-density lipoprotein cholesterol (HDL-C).MethodsData of 99 nicotine-dependent adult subjects who visited the smoking cessation outpatient services at International University of Health and Welfare Shioya Hospital were reviewed. Each subject was treated with varenicline titrated up to 1.0 mg twice daily for 12 weeks. Serum levels of oxHDL and HDL-C were repeatedly measured by enzyme-linked immunosorbent assay and enzymatic method, respectively.ResultsThe serum levels of oxHDL were significantly decreased from 163.2 ± 96.6 to 148.3 ± 80.7 U/mL (p = 0.034, n = 99). This effect was more prominent when the data of subjects in whom the treatment was objectively unsuccessful (exhaled carbon monoxide at 3 months ≥ 10 ppm) were omitted (from 166.6 ± 98.4 to 147.4 ± 80.6 U/mL; p = 0.0063, n = 93). In contrast, the serum levels of HDL-C were significantly increased (p = 0.0044, n = 99). There was a close relationship between the baseline levels of oxHDL and HDL-C (R = 0.45, p < 0.0001, n = 99). Changes in the levels of oxHDL were closely associated with changes in the levels of exhaled carbon monoxide in subjects in whom smoking cessation with varenicline was very effective (decrease in exhaled carbon monoxide by ≥ 15 ppm after treatment with varenicline; R = 0.42, p = 0.0052, n = 43).ConclusionsAlthough there was a close relationship between the baseline serum concentrations of oxHDL and HDL-C, smoking cessation decreased oxHDL and increased HDL-C. This effect on oxHDL may be associated with the effectiveness of smoking cessation.

Abstract An 81‐year‐old woman with a history of hypertension and Alzheimer's disease presented to the emergency department because of impaired consciousness. Physical examination revealed acute progressive generalized flaccid paralysis, hypertension, respiratory failure, and pupillary dilation. Although the patient did not complain of headache, head magnetic resonance angiography and magnetic resonance imaging showed multifocal segmental cerebral vasospasm and cerebral infarction in the left occipital lobe. Her family reported that although she did not have a license to cook pufferfish, she was in the habit of eating pufferfish. We subsequently detected tetrodotoxin in the patient's urine, and she was diagnosed with tetrodotoxin poisoning. As the symptoms of tetrodotoxin intoxication improved, head magnetic resonance angiography showed the disappearance of the multifocal segmental cerebral vasospasm. The patient's clinical course and imaging findings were consistent with reversible cerebral vasoconstriction syndrome (RCVS). Sympathetic overactivity after tetrodotoxin intoxication possibly caused the development of RCVS, and RCVS could not be ruled out even in the absence of the typical thunderclap headache. Magnetic resonance angiography is a useful modality when performing repeated examinations.

Background Arterial stiffness is an important predictor of cardiovascular events; however, indexes for measuring arterial stiffness have not been widely incorporated into routine clinical practice. This study aimed to determine whether the cardio‐ankle vascular index (CAVI), based on the blood pressure–independent stiffness parameter β and reflecting arterial stiffness from the origin of the ascending aorta, is a good predictor of cardiovascular events in patients with cardiovascular disease risk factors in a large prospective cohort. Methods and Results This multicenter prospective cohort study, commencing in May 2013, with a 5‐year follow‐up period, included patients (aged 40‒74 years) with cardiovascular disease risks. The primary outcome was the composite of cardiovascular death, nonfatal stroke, or nonfatal myocardial infarction. Among 2932 included patients, 2001 (68.3%) were men; the mean (SD) age at diagnosis was 63 (8) years. During the median follow‐up of 4.9 years, 82 participants experienced primary outcomes. The CAVI predicted the primary outcome (hazard ratio, 1.38; 95% CI, 1.16‒1.65; P

Abstract Background Adult height can serve as a disease marker. While taller stature has been reported to be linked to a decreased risk of cardiovascular disease (CVD), an influence of the height on CVD is not fully understood in specific populations of Asia, which has a lower incidence of CVD and lower stature than Western populations. Methods We conducted a systematic review using original articles of prospective cohort studies published in English, via the PubMed database, on the relationship between the height and mortality of CVD, including cerebrovascular disease, in Asian people. Results We selected four studies on heart/coronary disease and five studies on cerebrovascular disease. Regarding heart/coronary disease, two studies showed that taller stature was associated with a decreased mortality of heart disease in men or cardiovascular disease in women. The hazard ratios of other studies had not shown a clear significance but a decreased direction of taller stature to the mortality. Regarding cerebrovascular disease, most studies showed that taller stature was associated with a decreased mortality of total cerebrovascular diseases or stroke. In two studies, taller stature showed a decreased mortality of ischemic or hemorrhagic stroke. Conclusions Overall, adult height may be inversely predictive to the mortality of CVD, in particular cerebrovascular disease, in Asian people. While this seems to be a similar trend to that of Westerns, further studies are warranted.

Abstract Background Metabolic syndrome (MetS) and cancer are major public health problems worldwide. The relationship between MetS and cancer death is of great interest. We examined the predictive value of MetS for cancer mortality in Japan. Methods Study participants included 4495 men and 7028 women aged 18–90 years who were registered between 1992 and 1995 as part of the Jichi Medical School Cohort Study. We used a definition of MetS modified for the Japanese population. The primary outcome was cancer mortality. Additionally, the relationship between MetS and cancer-type specific mortality was examined. Analyses were conducted with Cox’s regression models adjusted for age, smoking status, alcohol drinking status, marital status, educational attainment, physical activity, occupational category, and menopausal status (only in women). Results During a mean follow-up of 18.5 years, 473 men and 297 women died from cancer. MetS was positively associated with cancer mortality in women (hazard ratio [HR], 1.69; 95% confidence interval [CI] 1.21–2.36), but not in men (HR, 1.21; 95% CI 0.90–1.62). Additionally, MetS was associated with a high risk of colorectal (HR, 3.48; 95% CI 1.68–7.22) and breast (HR, 11.90; 95% CI 2.25–62.84) cancer deaths in women. Conclusion MetS was a significant predictor of cancer mortality in women.

Background: Hepcidin-25 is a 25 amino acid hepatokine and a key regulator of iron metabolism related to iron deficiency anemia. Recent studies have suggested that an elevated hepcidin level is correlated with low energy availability. Leptin is an appetite-suppressing adipokine and has been reported to stimulate hepcidin production in animals and cultured cells. While leptin is modulated by exercise, it is known that endurance runners and sprinters practice different types of exercise. This study investigated and compared the relationships between hepcidin and leptin levels, iron status, and body fat to understand better the risk of iron deficiency anemia in endurance runners and sprinters.Methods: Thirty-six male college track and field athletes (15 endurance runners and 21 sprinters) were recruited for this study. Dietary intake, body composition, and blood levels of ferritin, hepcidin-25, leptin, and adiponectin were measured. Correlations between hepcidin levels and ferritin, body fat, leptin, and adiponectin were evaluated using Pearson's correlation coefficient for each group.Results: The endurance runners had lower hepcidin levels and higher leptin and adiponectin levels compared with sprinters. Ferritin was positively correlated with hepcidin-25 levels in both the endurance and sprinter groups. A positive correlation was observed between hepcidin-25 and body fat or leptin levels only in sprinters.Conclusion: This is the first study investigating the relationship between blood levels of hepcidin and leptin in athletes. The positive correlation between hepcidin-25 and leptin was observed in sprinters but not endurance runners.

Diabetic polyneuropathy (DPN) and endothelial dysfunction are prevalent complications of diabetes mellitus. Currently, there are two non-invasive markers for endothelial dysfunction: flow-mediated dilation and reactive hyperaemia peripheral arterial tonometry (RH-PAT). However, the relationship between diabetic small fibre neuropathy and macroangiopathy remains obscure thus far. Corneal confocal microscopy (CCM) has emerged as a new diagnostic modality to assess DPN, especially of small fibre. To clarify the relationship between diabetic small fibre neuropathy and vascular dysfunction, we aimed to determine the functions of peripheral nerves and blood vessels through clinical tests such as nerve conduction study, coefficient of variation in the R-R interval, CCM, and RH-PAT in 82 patients with type 2 diabetes. Forty healthy control subjects were also included to study corneal nerve parameters. Correlational and multiple linear regression analyses were performed to determine the associations between neuropathy indices and markers for vascular functions. The results revealed that patients with type 2 diabetes had significantly lower values for most variables of CCM than healthy control subjects. RH-PAT solely remained as an explanatory variable significant in multiple regression analysis for several CCM parameters and vice versa. Other vascular markers had no significant multiple regression with any CCM parameters. In conclusion, endothelial dysfunction as revealed by impaired RH-PAT was significantly associated with CCM parameters in patients with type 2 diabetes. This association may indicate that small fibre neuropathy results from impaired endothelial dysfunction in type 2 diabetes. CCM parameters may be considered surrogate markers of autonomic nerve damage, which is related to diabetic endothelial dysfunction. This study is the first to report the relationship between corneal nerve parameter as small fibre neuropathy in patients with type 2 diabetes and RH-PAT as a marker of endothelial dysfunction.

Guillain–Barré syndrome (GBS) usually has a good prognosis; however, patients may develop sequelae without prompt treatment. We herein describe an 81-year-old woman who developed acute-onset excruciating thigh pain and weakness in her lower extremities after spinal surgery. We diagnosed acute inflammatory demyelinating polyradiculoneuropathy by a nerve conduction study, which showed findings of demyelination without cerebrospinal fluid analysis because of a spinal prosthesis. Although anti-GM1 and anti-GalNAc-GD1a antibodies were positive, the patient was clinically diagnosed with acute inflammatory demyelinating polyradiculoneuropathy (a subtype of GBS), not acute motor axonal neuropathy. She recovered well with immunoglobulin therapy. A literature review of 18 cases revealed that unexplained weakness, areflexia, and numbness of the extremities after spinal surgery, a shorter time from spinal surgery to symptom onset to general GBS, abnormal nerve conduction study results, normal spinal imaging findings, and the development of atypical symptoms such as cranial and autonomic nerve syndrome and respiratory failure are useful for diagnosing GBS when cerebrospinal fluid examination cannot be performed after spinal surgery.

Objectives: The role of point-of-care testing (POCT) out of hospital, especially in home care and ambulatory care settings, is an issue meriting further research. We reviewed studies reporting cardiovascular events as a result of the implementation of B-type natriuretic peptide or N-terminal pro B-type natriuretic peptide POCT (BNP/NT-proBNP POCT) for heart disease patients in the settings. Design: Articles were searched via a PubMed engine until May 30, 2020. Results: In total, six studies were selected. Three studies involving ambulatory care used the POCT to refer patients with suspected heart diseases to a specialist. The other three used the tests in home care to monitor patients with heart failure. In ambulatory care, the randomized controlled trials, in which referrals were made to a specialist, showed that the group using POCT had significantly fewer cardiovascular outcomes, such as hospitalizations and deaths, than the non-use group. In home care, adverse outcomes were predicted from changes in BNP levels. Conclusions: In most studies, the use of BNP/NT-proBNP POCT in home care and ambulatory care settings demonstrated favorable results regarding the cardiovascular outcomes. The utility of POCT in the settings is suggested, while more investigations are required.

Background Whether circulating growth differentiation factor 15 (GDF‐15) levels differ according to smoking status and whether smoking modifies the relationship between GDF‐15 and mortality in patients with coronary artery disease are unclear. Methods and Results Using data from a multicenter, prospective cohort of 2418 patients with suspected or known coronary artery disease, we assessed the association between smoking status and GDF‐15 and the impact of smoking status on the association between GDF‐15 and all‐cause death. GDF‐15 was measured in 955 never smokers, 1035 former smokers, and 428 current smokers enrolled in the ANOX Study (Development of Novel Biomarkers Related to Angiogenesis or Oxidative Stress to Predict Cardiovascular Events). Patients were followed up during 3 years. The age of the patients ranged from 19 to 94 years; 67.2% were men. Never smokers exhibited significantly lower levels of GDF‐15 compared with former smokers and current smokers. Stepwise multiple linear regression analysis revealed that the log‐transformed GDF‐15 level was independently associated with both current smoking and former smoking. In the entire patient cohort, the GDF‐15 level was significantly associated with all‐cause death after adjusting for potential clinical confounders. This association was still significant in never smokers, former smokers, and current smokers. However, GDF‐15 provided incremental prognostic information to the model with potential clinical confounders and the established cardiovascular biomarkers in never smokers, but not in current smokers or in former smokers. Conclusions Not only current, but also former smoking was independently associated with higher levels of GDF‐15. The prognostic value of GDF‐15 on mortality was most pronounced in never smokers among patients with suspected or known coronary artery disease.

A 60-year-old man was admitted to our hospital with bilateral post auricular masses, first noticed 1 year earlier. Blood tests showed eosinophilia and high immunoglobulin E (IgE) levels, and cervical computed tomography showed 10-mm soft tissue masses with scattered lymphadenopathy. The tumors showed intermediate and high signal intensity on T1- and T2-weighted cervical magnetic resonance imaging, respectively. After mass resection, the tumors were diagnosed as Kimura’s disease (KD). Generally, KD affects young men; however, even in older patients, KD should be included as a differential diagnosis for head and neck tumors in patients with eosinophilia and high IgE.

Background VEGF‐D (vascular endothelial growth factor D) and VEGF‐C are secreted glycoproteins that can induce lymphangiogenesis and angiogenesis. They exhibit structural homology but have differential receptor binding and regulatory mechanisms. We recently demonstrated that the serum VEGF‐C level is inversely and independently associated with all‐cause mortality in patients with suspected or known coronary artery disease. We investigated whether VEGF‐D had distinct relationships with mortality and cardiovascular events in those patients. Methods and Results We performed a multicenter, prospective cohort study of 2418 patients with suspected or known coronary artery disease undergoing elective coronary angiography. The serum level of VEGF‐D was measured. The primary outcome was all‐cause death. The secondary outcomes were cardiovascular death and major adverse cardiovascular events defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. During the 3‐year follow‐up, 254 patients died from any cause, 88 died from cardiovascular disease, and 165 developed major adverse cardiovascular events. After adjustment for possible clinical confounders, cardiovascular biomarkers (N‐terminal pro‐B‐type natriuretic peptide, cardiac troponin‐I, and high‐sensitivity C‐reactive protein), and VEGF‐C, the VEGF‐D level was significantly associated with all‐cause death and cardiovascular death but not with major adverse cardiovascular events.. Moreover, the addition of VEGF‐D, either alone or in combination with VEGF‐C, to the model with possible clinical confounders and cardiovascular biomarkers significantly improved the prediction of all‐cause death but not that of cardiovascular death or major adverse cardiovascular events. Consistent results were observed within patients over 75 years old. Conclusions In patients with suspected or known coronary artery disease undergoing elective coronary angiography, an elevated VEGF‐D value seems to independently predict all‐cause mortality.

Abstract Background The board certification system serves as a quality assurance system for physicians, and its design and operation are important health policy issues. In Japan, board certification was established and operated independently by academic societies and has not been directly linked to reimbursement systems. The phenomenon of younger physicians seeking specialist careers has raised concerns about acceleration of the tendency of fewer physicians working in rural areas and the maldistribution of physicians. Little is known about the associations between physicians’ geographical migration patterns and board certification status changes or between the continuation of urban/rural practice and the maintenance of board certification. This study aimed to identify these associations and to discuss their policy implications. Methods We analyzed 2012 and 2014 data from the Survey of Physicians, Dentists, and Pharmacists, a national census survey. To analyze geographical migration patterns, transitions in practice location (rural, intermediate, and urban) were analyzed by board certification status change (new, lost, consistently certified, and consistently uncertified). Logistic regression analysis was conducted to assess whether the odds of migrating to more urban/rural municipalities were associated with board certification status changes, adjusting for covariates, and whether practicing in a rural area was associated with maintaining board certification. Results Among 18,726 newly board-certified physicians, 94.9% (13,435/14,150) of those working in urban areas before certification remained in urban areas, whereas 64.6% (393/608) of those working in rural areas stayed in rural areas. Those who were newly certified had higher odds of moving to more urban areas, adjusting for covariates. Those who stayed in rural areas showed lower odds of maintaining board certification, adjusting for covariates. Conclusions Newly board-certified physicians are more likely to migrate to other types of areas, particularly more urban areas, than other physicians. Allocating more training quotas to rural areas could be one option for leveling the distribution of specialists. It also appeared that those practicing in rural areas have difficulty maintaining their certification, so the need to establish a support system for already-certified physicians in rural areas should be emphasized.

Background: Globally, few published studies have tracked the temporal trend of dioxin levels in the human body since 2000. This study describes the annual trend of dioxin levels in human breast milk in Japanese mothers from 1998 through 2015. Methods: An observational study was conducted from 1998 through 2015. Participants were 1,194 healthy mothers following their first delivery who were recruited annually in Japan. Breast milk samples obtained from participants were analyzed using gas chromatography and mass spectrometry for dioxins, including polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (PCBs). Results: Mean age was 29.5 years, and 53% of participants were 20–25 years old. A declining trend in total dioxin levels was found, from a peak of 20.8 pg toxic equivalence (TEQ)/g fat in 1998 to 7.2 pg TEQ/g fat in 2014. Data from the last 5 years of the study indicated a plateau at minimal levels. In contrast, an increasing trend was found in the mean age of participants during the last 5 years. Although significantly higher dioxin levels were observed in samples from older participants, an upward trend in dioxin levels was not observed, indicating that dietary and environmental exposure to dioxins had greatly diminished in recent years. Conclusions: Dioxin levels in human breast milk may be approaching a minimum in recent years in Japan. The findings may contribute to global reference levels for environmental pollution of dioxins, which remains a problem for many developing countries.

Abstract Background In Japan, although many suicidal studies were previously conducted in tertiary emergency department (ED) settings, no published studies have reported on suicidal patients presenting to the secondary EDs. The aim of the study was to describe the characteristics of suicidal patients and the referral rates to a psychiatrist overall and by type of facility. Methods Questionnaires were sent to all secondary and tertiary EDs in Tochigi prefecture, Japan. Data were collected for cases who presented in September 2009. Chi-square, Fisher’s exact, and t-tests compared the results by gender and type of ED. Results All 74 EDs responded to the survey. There were 81 patients who attempted or died by suicide (36 men and 45 women). The most common method of suicide attempt was drug overdose (57%) followed by stabbing (17%). About a half used prescription drugs to attempt or die by suicide. The majority had a history of psychiatric disorders, and 35% had previous suicide attempt. About a half were admitted to medical or surgical unit; 33% were discharged home; and 9% died. After excluding those who died, 53% were referred to a psychiatrist, but 47% were not referred to a psychiatrist. The referral rate was lower for cases seen at secondary EDs (38%) compared to tertiary EDs (67%). Conclusion Although professional organizations suggest that suicidal patients are seen by a psychiatrist, many were not, especially at secondary EDs. Further research is needed to assure that suicidal patients presenting to EDs receive appropriate psychiatric assessment and follow-up after discharge.

Abstract Calciprotein particles (CPP) are solid-phase calcium-phosphate bound to serum protein fetuin-A and dispersed as colloids in the blood. Recent clinical studies indicated that serum CPP levels were increased with decline of renal function and associated with inflammation and vascular calcification. However, CPP assays used in these studies measured only a part of CPP over a certain particle size and density. Here we show that such CPP are mostly artifacts generated during processing of serum samples in vitro. The native CPP in fresh plasma are smaller in size and lower in density than those artifactual CPP, composed of fetuin-A carrying amorphous and/or crystalline calcium-phosphate, and increased primarily with serum phosphate levels. We have identified several physicochemical factors that promote aggregation/dissolution of CPP and transition of the calcium-phosphate from the amorphous phase to the crystalline phase in vitro, including addition of anti-coagulants, composition of buffer for sample dilution, the number of freeze-thaw cycles, the speed for sample freezing, and how many hours the samples were left at what temperature. Therefore, it is of critical importance to standardize these factors during sample preparation in clinical studies on CPP and to investigate the biological activity of the native CPP.

Background: Previous systematic reviews have not clarified the effect of postoperative coffee consumption on the incidence of postoperative ileus (POI) and the length of hospital stay (LOS). We aimed to assess its effect on these postoperative outcomes. Methods: Studies evaluating postoperative coffee consumption were searched using electronic databases until September 2021 to perform random-effect meta-analysis. The quality of evidence was assessed using the Cochrane risk-of-bias tool. Caffeinated and decaffeinated coffee were also compared. Results: Thirteen trials (1246 patients) and nine ongoing trials were included. Of the 13 trials, 6 were on colorectal surgery, 5 on caesarean section, and 2 on gynecological surgery. Coffee reduced the time to first defecation (mean difference (MD) −10.1 min; 95% confidence interval (CI) = −14.5 to −5.6), POI (risk ratio 0.42; 95% CI = 0.26 to 0.69); and LOS (MD −1.5; 95% CI = −2.7 to −0.3). This trend was similar in colorectal and gynecological surgeries. Coffee had no adverse effects. There was no difference in POI or LOS between caffeinated and decaffeinated coffee (p > 0.05). The certainty of evidence was low to moderate. Conclusion: This review showed that postoperative coffee consumption, regardless of caffeine content, likely reduces POI and LOS after colorectal and gynecological surgery.

Abstract Background Carnitine is reported to improve insulin resistance and reduce oxidative stress. Hyperglycemia and increased oxidative stress are well known to promote the production of advanced glycation end products (AGEs) that can lead to arteriosclerosis in patients with maintenance hemodialysis (HD). In the present study, we aimed to determine whether decreased level of serum carnitine accelerated arteriosclerosis and to clarify the relationships between carnitine, AGEs, and arteriosclerosis in HD patients. Methods We recruited 116 patients (65 men and 51 women, 62 ± 13 years) undergoing HD three times a week. We measured pre-HD serum free carnitine prior to the first weekly session. AGE level was quantitatively evaluated by measuring skin autofluorescence (SAF) with AGE reader. Arteriosclerosis was evaluated by measuring carotid intima-media thickness (cIMT). Relationships between free carnitine, SAF, and cIMT were analyzed, and significant limiting factors for arteriosclerosis were identified using univariate and multivariate regression analyses. Results Free carnitine ranged from 14.9 to 53.3 μmol/L (mean, 28.6 ± 8.1 μmol/L). Free carnitine was negatively correlated with SAF (r = − 0.223, P = 0.017) and cIMT (r = − 0.252, P = 0.006). SAF was positively correlated with cIMT (r = 0.263, P = 0.005). Free carnitine was identified as a significant independent limiting factor for cIMT (β = -0.194, P = 0.037). Conclusions Decreased level of serum carnitine might lead to the progression of arteriosclerosis via the AGE accumulation in HD patients.

Oxidative stress is a driving factor in the pathophysiology of chronic obstructive pulmonary disease (COPD). While paraoxonase 1 (PON1) is an antioxidant enzyme and a potential biomarker of this disease, data regarding the status of PON-1 in COPD are inconclusive. In this regard, to shed light on this issue, we performed a meta-analysis of data on PON1 activity in COPD. Electronic databases (MEDLINE, Embase and CENTRAL) were searched for available studies on PON1 activity in patients with stable COPD published before October 2021. A meta-analysis was performed using random-effects models. Twelve studies (12 studies on paraoxonase and three on arylesterase) were identified. Patients with COPD had lower levels of paraoxonase activity (standard mean difference [SMD] −0.77, 95% confidence interval [CI] −1.35 to −0.18) and arylesterase activity (SMD −1.15, 95% CI −1.95 to −0.36) in comparison to healthy controls. In subgroup analyses, paraoxonase activity was lower in patients of studies as consisted of mainly non-severe COPD (SMD −1.42, 95% CI −2.04 to −0.79) and, by contrast, slightly higher in patients of studies including severe COPD (SMD 0.33, 95% CI 0.02 to 0.64) in comparison to healthy controls. Arylesterase activity showed a similar trend. Overall, PON1 activity was lower in patients with COPD, suggesting that PON1-related antioxidant defense is impaired in COPD. Future studies are warranted.

Hepcidin-25 is suggested as a surrogate iron status marker in athletes who show exercise-induced anemia; however, the implications of hepcidin concentration in this population remain poorly understood. This study aimed to investigate the relationship between hepcidin and body fat levels in rugby football players. We included 40 male university rugby football players (RUG) and 40 non-athlete controls. All participants underwent an anthropometric analysis and blood testing that included both hepcidin-25 and ferritin levels. The hepcidin-25 level was slightly (11.6%, p = 0.50) higher, and the ferritin level was significantly (35.9%, p < 0.05) lower, in the RUG group than in controls. The hepcidin-25 to-ferritin ratio was significantly higher (62.5%, p < 0.05) in the RUG group. While significant U-shaped correlations were observed between the body fat and ferritin levels in both groups, the correlations between the hepcidin levels and fat mass index were significantly higher in the RUG group (RUG: r = 0.79, controls: r = 0.45). Notably, the RUG with the lower fat mass index group had a higher hepcidin-25 level, lower ferritin level, and then significantly higher hepcidin-25/ferritin ratio. The hepcidin-25/ferritin ratio may serve as a biomarker for iron status in RUG, especially RUG with lower fat mass.