小谷 和彦

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.

Chronic renal failure (CRF) is associated with the development of cardiovascular disease (CVD). Paraoxonase 1 (PON1), an antioxidant enzyme, shows cardioprotective properties and has been proposed as a therapeutic marker for CRF. A systematic analysis of the literature assessing the association between PON1 activity and renal replacement therapy (RRT) of CRF is currently lacking. Therefore, we set out to perform a meta-analysis of the available data on PON1 in RRT of CRF. We searched three electronic databases for studies on PON1 activity in CRF patients with RRT such as hemodialysis (HD), peritoneal dialysis (PD), or renal transplantation (RTx), published before June 2023. A random-effects and network meta-analysis were performed. A total of 53 studies were eligibly identified. Compared to CRF patients without RRT, RTx patients had higher paraoxonase activity (standard mean difference (SMD), 1.76, 95% confidence interval (CI), 0.76–2.75), followed by HD (SMD, 0.73; 95% CI, 0.02–1.45) and PD patients. Likewise, RTx patients had higher arylesterase activity (SMD, 1.84, 95% CI, 0.18–3.50), followed by HD and PD patients. Also, paraoxonase activity was increased after HD (SMD, 0.59, 95% CI, 0.16–1.03). In conclusion, the overall data demonstrated that PON1 activity is higher in CRF patients with RRT, particularly RTx, followed by that of HD and PD. Measuring PON1 activity can also be included to the paraclinical toolbox for the management of RRT, in addition to the understanding of CRF-related pathophysiology. Regarding the selection of RRT types and their potential to prevent CVD, more research is required.

BACKGROUND: Preoperative stoma site marking reduces the incidence of complications from elective surgery. However, the impact of stoma site marking in emergency patients with colorectal perforation remains unclear. This study aimed to assess the impact of stoma site marking on morbidity and mortality in patients with colorectal perforation who underwent emergency surgery. METHODS: This retrospective cohort study used the Japanese Diagnosis Procedure Combination inpatient database from April 1, 2012, to March 31, 2020. We identified patients who underwent emergency surgery for colorectal perforation. We compared outcomes between those with and without stoma site marking using propensity score matching to adjust for confounding factors. The primary outcome was the overall complication rate, and the secondary outcomes were stoma-related, surgical, and medical complications and 30-day mortality. RESULTS: We identified 21,153 patients (682 with stoma site marking and 20,471 without stoma site marking) and grouped them into 682 pairs using propensity score matching. The overall complication rates were 23.5% and 21.4% in the groups with and without stoma site marking, respectively (p = 0.40). Stoma site marking was not associated with a decrease in stoma-related, surgical, or medical complications. The 30-day mortality did not differ significantly between the groups with and without stoma site marking (7.9% vs. 8.4%, p = 0.843). CONCLUSIONS: Preoperative stoma site marking was not associated with a reduction in morbidity and mortality in patients with colorectal perforation who underwent emergency surgery.

Aim: Serum levels of cholesterol absorption and synthesis markers have been associated with cardiovascular risk in the United States and European countries. In this study, we examined the relevance of these biomarkers and the presence of cardiovascular disease (CVD) in Japanese individuals. Methods: The CACHE consortium, comprising of 13 research groups in Japan possessing data on campesterol, an absorption marker, and lathosterol, a synthesis marker measured by gas chromatography, compiled the clinical data using the REDCap system. Results: Among the 2,944 individuals in the CACHE population, those with missing campesterol or lathosterol data were excluded. This cross-sectional study was able to analyze data from 2,895 individuals, including 339 coronary artery disease (CAD) patients, 108 cerebrovascular disease (CeVD) patients, and 88 peripheral artery disease (PAD) patients. The median age was 57 years, 43% were female, and the median low-density lipoprotein cholesterol and triglyceride levels were 118 mg/dL and 98 mg/dL, respectively. We assessed the associations of campesterol, lathosterol, and the ratio of campesterol to lathosterol (Campe/Latho ratio) with the odds of CVD using multivariable-adjusted nonlinear regression models. The prevalence of CVD, especially CAD, showed positive, inverse, and positive associations with campesterol, lathosterol, and the Campe/Latho ratio, respectively. These associations remained significant even after excluding individuals using statins and/or ezetimibe. The associations of the cholesterol biomarkers with PAD were determined weaker than those with CAD. Contrarily, no significant association was noted between cholesterol metabolism biomarkers and CeVD. Conclusion: This study showed that both high cholesterol absorption and low cholesterol synthesis biomarker levels were associated with high odds of CVD, especially CAD.

Oxidative stress is known to be associated with the pathophysiology of chronic kidney disease (CKD). Paraoxonase 1 (PON1) is an antioxidant enzyme that has been proposed as a biomarker for CKD. While several studies have reported an association between serum PON1 activity and CKD, consensus based on systematically analyzed data remains necessary. We set out to conduct a meta-analysis of literature on PON1 in CKD. Electronic databases, such as MEDLINE, Embase and CENTRAL, were searched for available studies on PON1 activity in patients with CKD (without dialysis) as published before December 2022. A random-effects meta-analysis was performed. In total, 24 studies (22 studies on paraoxonase and 11 on arylesterase activity) were eligibly identified. Patients with CKD showed a lower activity of paraoxonase (standard mean difference [SMD], −1.72; 95% confidence interval [CI], −2.15 to −1.29) and arylesterase (SMD, −2.60; 95%CI, −3.96 to −1.24) than healthy controls. In the subgroup analyses, paraoxonase activity was lower in chronic kidney failure (CKF), an advanced stage of CKD, than in non-CKF. In summary, PON1 activity is low in patients with CKD, suggesting that the antioxidant defense by PON1 is impaired in CKD. The decrease in enzyme activity is pronounced in advanced CKD showing some variability depending on the substrate employed to measure PON1 activity. Further studies are warranted.

AIM: Risk of cardiovascular disease is increased in patients with diabetes mellitus (DM). Cholesterol metabolism (hepatic synthesis and intestinal absorption) is known to be associated with cardiovascular risk. Next, we examined the association of DM with cholesterol absorption/synthesis. METHODS: The CACHE Consortium, which is comprised of 13 research groups in Japan possessing data of lathosterol (Latho, synthesis marker) and campesterol (Campe, absorption marker) measured by gas chromatography, compiled the clinical data using the REDCap system. Among the 3597 records, data from 2944 individuals were used for several analyses including this study. RESULTS: This study analyzed data from eligible 2182 individuals including 830 patients with DM; 42.2% were female, median age was 59 years, and median HbA1c of patients with DM was 7.0%. There was no difference in Latho between DM and non-DM individuals. Campe and Campe/Latho ratio were significantly lower in DM individuals than in non-DM individuals. When the associations of glycemic control markers with these markers were analyzed with multivariable-adjusted regression model using restricted cubic splines, Campe and Campe/Latho ratio showed inverse associations with glucose levels and HbA1c. However, Latho showed an inverted U-shaped association with plasma glucose, whereas Latho showed a U-shaped association with HbA1c. These associations remained even after excluding statin and/or ezetimibe users. CONCLUSION: We demonstrated that DM and hyperglycemia were independent factors for lower cholesterol absorption marker levels regardless of statin/ezetimibe use.

BACKGROUND: The 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). METHODS: Data 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. RESULTS: The 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). CONCLUSIONS: Although 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.

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.