The 2023 Guidelines for the management and treatment of glucocorticoid-induced osteoporosis.

INTRODUCTION: Although synthetic glucocorticoids (GCs) are commonly used to treat autoimmune and other diseases, GC induced osteoporosis (GIOP) which accounts for 25% of the adverse reactions, causes fractures in 30-50% of patients, and markedly decreases their quality of life. In 2014, the Japanese Society for Bone and Mineral Research (JSBMR) published the revised guidelines for the management and treatment of steroid-induced osteoporosis, providing the treatment criteria based on scores of risk factors, including previous fractures, age, GC doses, and bone mineral density, for patients aged ≥18 years who are receiving GC therapy or scheduled to receive GC therapy for ≥3 months. MATERIALS AND METHODS: The Committee on the revision of the guidelines for the management and treatment of GIOP of the JSBMR prepared 17 clinical questions (CQs) according to the GRADE approach and revised the guidelines for the management and treatment of GIOP through systematic reviews and consensus conferences using the Delphi method. RESULTS: Bisphosphonates (oral and injectable formulations), anti-RANKL antibody teriparatide, eldecalcitol, or selective estrogen receptor modulators are recommended for patients who has received or scheduled for GC therapy with risk factor scores of ≥3. It is recommended that osteoporosis medication is started concomitantly with the GC therapy for the prevention of fragility fractures in elderly patients. CONCLUSION: The 2023 guidelines for the management and treatment of GIOP was developed through systematic reviews and consensus conferences using the Delphi method.

The effects of dienogest and combined oral contraceptives on protein S-specific activity in endometriosis patients.

OBJECTIVE: One serious side effect of combined oral contraceptives (COCs) is venous thromboembolism. Reduced activity in activated protein C-related coagulation pathways is attributable to low protein S activity in one-third of Japanese patients with deep vein thrombosis. Herer, we quantified the behavior of protein S-specific activity in response to dienogest (DNG) and COCs using the protein S-specific activity assay system to explore its potential utility as a thrombosis marker. STUDY DESIGN: This was a prospective cohort study. Female patients aged 20 - 49 years who were starting drug treatment for endometriosis using DNG or COCs were enrolled. Blood samples were taken before treatment and at the first, third, and sixth months of treatment. To analyze the primary endpoints, changes in total protein S antigen levels, total protein S activity, and protein S-specific activity from baseline to each time point were estimated using a linear mixed-effects model. All statistical analyses were performed in the SAS software version 9.4 (SAS Institute, Cary, NC). A two-sided P < 0.05 was considered statistically significant. RESULTS: 64 patients took DNG and 34 patients took COCs. Protein S-specific activity did not change significantly from baseline in the six months after treatment started in either group. In the DNG group, total protein S activity and total protein S antigen levels increased slightly from baseline levels after the treatment. The means for total protein S activity and total protein S antigen levels in the COC group remained within reference limits, but they both decreased markedly in the first month and stayed low. Protein S-specific activity in four women remaind below the reference limit throughout the whole study period, suggesting they may have potential protein S deficiencies. CONCLUSION: The effects of DNG on protein S were negligible, though both total protein S activity and antigen levels decreased soon after COC treatment began and remained low. As there was no VTE event during the study, further studies with larger numbers of patients will be needed to confirm that protein S-specific activity can be a surrogate maker of VTE risk.

Corrigendum: What kind of intervention is effective for improving subjective well-being among workers? A systematic review and meta-analysis of randomized controlled trials.

[This corrects the article DOI: 10.3389/fpsyg.2020.528656.].

Chronic kidney disease prevalence and awareness in middle age and young old: Regional comparative study in Japan.

AIM: Patients with chronic kidney disease are not aware of the illness because of its asymptomatic nature, but the association of disease progression and awareness in general population has not been sufficiently analysed on a large scale. METHODS: We analysed the nationwide annual specific health checkup covering more than a half of the overall population at aged 40-74 in Japan, approximately 29.4 million people as of 2018, in combination with parameters to represent regional characteristics. RESULTS: The rate of the examinees with kidney dysfunction, an estimated glomerular filtration rate of <45 mL/min/1.73 m2 , was 1.0%, while that of examinees with of dipstick proteinuria ≥ (+) was 3.7%. Next, we conducted a regional comparative study on 335 medical administrative areas divided in the country. The regional rate of examinees aged 65-74 over the total examinees was positively correlated with the prevalence of kidney dysfunction (r = 0.72, p < .0001). Additionally, the mean rate of examinees aware of their 'chronic kidney failure' was 0.6%, and the awareness rate was correlated with the prevalence of both kidney dysfunction (r = 0.36, p < .001) and positive dipstick proteinuria (r = 0.31, p < .001) in those aged 65-74 at the regional level. Association of nephrology care resources with the prevalence or awareness was unclear at the regional level. CONCLUSION: We found a regional association of chronic kidney disease prevalence and awareness in a recent young old population in Japan. Further studies are needed to evaluate the patient screen and referral at the individual level.

Work-related psychosocial factors and inflammatory markers: A systematic review and meta-analysis.

OBJECTIVE: We conducted a systematic review and meta-analysis to evaluate the prospective effect of adverse work-related psychosocial factors on increases in inflammatory markers. METHODS: A systematic literature search was conducted in PubMed, Embase, PsycINFO, PsycARTICLES, and the Japan Medical Abstracts Society database. Studies were eligible for inclusion if they examined associations between work-related psychosocial factors and inflammatory markers (interleukin-6, tumor necrosis factor-alpha, and C-reactive protein), used longitudinal or prospective cohort designs, were conducted among workers, were original articles written in English or Japanese, and were published up to 2017 for the first search, October 2020 for the second, and November 2022 for the third. A meta-analysis was conducted using a random-effects model to assess the pooled effect size for the associations. A meta-regression analysis was used to estimate the association between length of follow-up and effect size. The ROBINS-I tool was used to assess risk of bias. RESULTS: Of the 11,121 studies identified in the first search, 29,135 studies from the second, and 9448 studies from the third, eleven were eligible for this review and meta-analysis. The pooled coefficient between adverse work-related psychosocial factors and inflammatory markers was significant and positive (ß = 0.014, 95% confidence interval: 0.005-0.023). However, a clear association was only observed for interleukin-6, and all the studies included had serious risks of bias. Meta-regression showed the effect size decreased depending on the follow-up period. CONCLUSION: This study revealed a weak positive association between adverse work-related psychosocial factors and increases in inflammatory markers. TRIAL REGISTRATION: PROSPERO CRD42018081553 (https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=81553).

A proposed definition of participatory organizational interventions.

Participatory organizational interventions offer an effective way to promote occupational safety and health. Despite an increasing number of studies, a common definition of participatory organizational interventions has yet to be established. Therefore, we aimed to form a definition using the following process. First, we developed a tentative draft definition of organizational interventions and participatory elements, based on the relevant literature. The tentative definition was revised in several rounds of an extensive discussion by the authors. This resulted in the draft definition. We asked 15 selected international experts in occupational safety and health to review and comment on the draft definition. We carefully reviewed their comments, and formulated our final proposed definition. To summarize the key points of the final version of the definition, organizational interventions are planned actions that primarily directly target working conditions with the aim of promoting and maintaining of the highest degree of physical, mental, and social well-being of workers in all occupations. In addition, as participatory elements of organizational interventions in the final definition, ideally, all workers participate in every step of the intervention, while participating in part of the steps of the intervention in some cases. Furthermore, in principle, all workers participate in each step of intervention, while it is also acceptable that only elected representatives among workers participate in the intervention.

Usage of the Brief Job Stress Questionnaire: A Systematic Review of a Comprehensive Job Stress Questionnaire in Japan from 2003 to 2021.

The Brief Job Stress Questionnaire (BJSQ) is used widely in occupational health studies and practice. Summarizing scientific production based on measurement is crucial. This study aimed to systematically review observational studies that used the BJSQ and the New BJSQ to show their usability. A systematic search was conducted for studies investigating relationships between the BJSQ or the New BJSQ subscales and other validated measurements on 13 September 2021, in various literature databases. The BJSQ subscales, scoring methods, and other validated measurements in the studies were qualitatively summarized. In total, 145 published reports between 2003 and 2021 were included. Among the BJSQ subscales, job stressors (n = 95) such as quantitative job overload (n = 65) and job control (n = 64) were most often used. The subscales were utilized to investigate the relationships with several other measurements. Five reports used subscales from the New BJSQ. In the last two decades, the BJSQ and the New BJSQ help measure psychosocial factors (PF) at work and contribute to the publication of scientific papers in the occupational health field. This study would encourage the utilization of the questionnaires for future research and practice.

Bone marrow stromal cell antigen-1 (CD157) regulated by sphingosine kinase 2 mediates kidney fibrosis.

Chronic kidney disease is a progressive disease that may lead to end-stage renal disease. Interstitial fibrosis develops as the disease progresses. Therapies that focus on fibrosis to delay or reverse progressive renal failure are limited. We and others showed that sphingosine kinase 2-deficient mice (Sphk2 -/-) develop less fibrosis in mouse models of kidney fibrosis. Sphingosine kinase2 (SphK2), one of two sphingosine kinases that produce sphingosine 1-phosphate (S1P), is primarily located in the nucleus. S1P produced by SphK2 inhibits histone deacetylase (HDAC) and changes histone acetylation status, which can lead to altered target gene expression. We hypothesized that Sphk2 epigenetically regulates downstream genes to induce fibrosis, and we performed a comprehensive analysis using the combination of RNA-seq and ChIP-seq. Bst1/CD157 was identified as a gene that is regulated by SphK2 through a change in histone acetylation level, and Bst1 -/- mice were found to develop less renal fibrosis after unilateral ischemia-reperfusion injury, a mouse model of kidney fibrosis. Although Bst1 is a cell-surface molecule that has a wide variety of functions through its varied enzymatic activities and downstream intracellular signaling pathways, no studies on the role of Bst1 in kidney diseases have been reported previously. In the current study, we demonstrated that Bst1 is a gene that is regulated by SphK2 through epigenetic change and is critical in kidney fibrosis.

The impact of workplace psychosocial factors on menstrual disorders and infertility: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Workplace environment, especially psychosocial factors at work such as job strain, workplace social support, and shift work, may affect the menstrual abnormalities and fertility of female workers. However, the association between psychosocial factors at work and menstrual abnormalities or fertility is not well understood. To address this relationship, we will conduct a systematic review and a meta-analysis of the literature that has utilized a longitudinal or prospective cohort design. METHODS AND ANALYSIS: The inclusion criteria for this systematic review and meta-analysis are defined as follows: (P) adult female workers (over 18 years old), (E) the presence of adverse psychosocial factors at work, (C) the absence of adverse psychosocial factors at work, and (O) any menstrual cycle disorders, menstrual-related symptoms, or fertility. The MEDLINE, Embase, PsycINFO, PsycArticles, and Japan Medical Abstracts Society electronic databases will be used to search for published studies. The statistical synthesis of the studies included in the meta-analysis will be conducted to estimate pooled coefficients and 95% CIs. For the main analysis, we will synthesize measures of association between psychosocial factors at work and menstrual-related disorders/symptoms. At least three eligible studies will have to be gathered to conduct a meta-analysis; otherwise (i.e., if only one or two studies will be eligible and included), the results will be presented in a narrative table. We will use the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) to determine the quality of selected studies. To assess meta-bias, Egger's test, along with a funnel plot, will be used to check for publication bias. Lastly, we will examine heterogeneity using the χ2 test with Cochran's Q statistic and I2. ETHICS AND DISSEMINATION: The results and findings will be submitted and published in a scientific peer-reviewed journal and will be disseminated broadly to researchers and policymakers interested in the translatability of scientific evidence into good practices. SYSTEMATIC REVIEW REGISTRATION: The study protocol was registered at the UMIN registry (registration number: UMIN000039488). The registration date is on 14 Feb 2020. URL: https://upload.umin.ac.jp/cgi-bin/ctr/ctr_view_reg.cgi?recptno=R000044704.

STRENGTH AND LIMITATIONS OF THIS STUDY: • This systematic review and a meta-analysis will investigate the associations between psychosocial factors at work and menstrual abnormalities or fertility. • This review will include only the literature that has utilized a longitudinal design. • Various outcomes related to reproductive health in female workers will be examined (e.g., fertility, premenstrual symptoms, cycle disorders, menopausal symptoms).

Workplace Social Support and Reduced Psychological Distress: A 1-Year Occupational Cohort Study.

OBJECTIVE: There is little evidence that workplace social support can relieve workers' mental health problems. Therefore, we examined whether social support from coworkers and supervisors was associated with reduced serious psychological distress among employees. METHODS: We used two-wave panel data from 13 Japanese companies. The baseline survey was conducted in 2011, and the follow-up survey 1 year later. From 9889 respondents, we selected 759 who had psychological distress at baseline, defined as ≥13 on the Kessler Psychological Distress Scale (K6). RESULTS: Increased coworker support was significantly associated with employees' reduced psychological distress (odds ratio, 3.51; 95% confidence interval, 2.17 to 5.68). The association between increased supervisor support and reduced psychological distress was nonsignificant (odds ratio, 1.32, 95% confidence interval, 0.85 to 2.04). CONCLUSION: Encouraging coworker support may contribute to the secondary prevention of mental health problems among employees.

Neutrophil Protein Kinase R Mediates Endothelial Adhesion and Migration by the Promotion of Neutrophil Actin Polymerization.

Neutrophils protect against bacterial and fungal infections, but tight regulation of cell activation is essential for avoiding tissue damage in autoimmune disorders. Protein kinase R (PKR) is a serine/threonine kinase originally characterized by its role in the defense mechanisms against viral infection. Although PKR is involved in the signaling pathways of neurodegenerative diseases and metabolic disorders, its function in neutrophils is not well delineated. In this study, we demonstrate that human neutrophil PKR mediates adhesion to endothelial cells under physiological flow conditions but does not mediate rolling on those cells. Also, neutrophil PKR activation contributes to migration toward chemoattractants. Mechanistically, neutrophil PKR mediates the cell spreading and binding to ICAM-1 in static condition. Moreover, Ab microarray reveals that calcium/calmodulin-dependent protein kinase II is phosphorylated downstream of PKR and affects actin polymerization that is a cytoskeleton rearrangement indispensable for neutrophil migration induced by fMLF. In vivo, neutrophil recruitment into the dorsal air pouch of mice is reduced by PKR inhibitor treatment. Also, in mice with nephrotoxic serum nephritis, the compound treatment suppresses neutrophil accumulation in kidney glomerulus and subsequent development of albuminuria. Thus, in vascular inflammation, neutrophil PKR plays a critical role in the recruitment process, including endothelial adhesion and migration via leukocyte actin polymerization.

Regional Distribution of Cardiologists and Prescription Patterns of Sodium-Glucose Transporter-2 Inhibitors in Japan.

The clinical evidence is accumulating since 2015 that anti-diabetic sodium-glucose cotransporter 2 (SGLT2) inhibitors have the beneficial effect of cardiovascular and, recently, renal protection. Although it is not well analyzed how the transfer of this new evidence into daily practice has expedited, we hypothesize that the recent usage of the drugs is positively associated with several certified cardiologists in each region.The 2016 annual and 2016-2017 increased number of SGLT2 inhibitor tablets, based on the National Database of Health Insurance Claims and Specific Health Checkups of Japan, were divided by the estimated number of patients with type 2 diabetes mellitus for each of the 47 prefectures. Then, regression analyses were performed to investigate the potential association of the number of certified cardiologists with the drug prescription.The 2016 prescription of ipragliflozin, dapagliflozin, luseogliflozin, canagliflozin, and empagliflozin was 2.7- to 4.4-fold different between prefectures. The 2016-2017 increased prescription volume also varied among prefectures by as large as 7.3-fold for ipragliflozin. Regression analysis revealed that the annual and increased prescription volume of all the SGLT2 inhibitors except luseogliflozin were higher in regions with more certified cardiologists (P < 0.05), even after adjusting for regional parameters.In conclusion, the regional number of certified cardiologists was positively associated with a 2016 annual of and 2016-2017 increase in SGLT2 inhibitor prescription amount, implying an early adopter role of clinical experts in healthcare delivery.

[Expected research in the workplace among Japanese female workers: A cross-sectional online survey based on the framework of patient and public involvement].

OBJECTIVES: This study aimed to investigate the work-related health and social problems among Japanese female workers and the expected research in the workplace. METHOD: A cross-sectional study using an Internet survey was conducted on female workers in Japan. Using an original questionnaire, we obtained data on "a system that can be used by female workers," "female workers' problems (physical symptoms, mental symptoms, menstrual problems, pregnancy/childbirth problems, work-life balance, etc.)," and "expected research in the workplace." The last two were compared using the chi-square test and considering demographic characteristics (age, marital status, having children, having preschool children, employment status, occupation). We conducted the chi-square test to examine the relationship between the presence of symptoms and four expected studies. The survey was carried out in July 2019 by using a patient and public involvement (PPI) framework in medical research. RESULTS: We obtained 416 responses that highlighted that those who have work-related problems also have physical symptoms (89%), menstrual problems (65%), psychiatric symptoms (49%), and work-life balance problems (39%), followed by career as well as pregnancy and childbirth concerns (38%). Regarding the system, the respondents' usage rate was an infertility treatment communication card (0%), flextime and telework (1 to 3%), menstrual leave (4%), and short-time work system (8%). Expected workplace studies included "Research to ease stiff shoulders and back pain" (45%), "Research to improve women's mental health" (41%), "Research on menstruation and work performance" (35%), and "Research to improve work-life balance" (34%). Expectations for research on "mental health" and "menstruation" were high among subjects in their 20s and 30s, with no spouse or children, and working full-time. Among those who lived with preschoolers, expectations for research on "mental support after childbirth," "physical support after childbirth," and "prevention of postpartum depression" were significantly higher, but research related to work-life balance was not remarkably different. There was a significant association between having menstrual problems, work-life balance challenges, and study expectations. However, the percentage of those experiencing certain symptoms who expected workplace studies was about 48%. CONCLUSIONS: Menstruation-related symptoms are frequently observed to make work difficult and it is expected that health issues, such as mental and physical conditions related to gynecology, will be the subject of future research regarding female workers. However, discrepancies between having difficulties and whether or not they wish to accept research in the workplace should be carefully considered in each context.

What Kind of Intervention Is Effective for Improving Subjective Well-Being Among Workers? A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objectives: This study aimed to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to improve subjective well-being (SWB), including evaluative, hedonic, and eudemonic well-being, and the mental component of quality of life (QOL) of working population. Methods: A literature search was conducted, using PubMed, Embase, PsycINFO, and PsycARTICLES. Eligible studies included those that were RCTs of any intervention, conducted among healthy workers, measured SWB as a primary outcome, and original articles in English. Study characteristics, intervention, outcomes, and results on SWB outcomes were extracted by the investigators independently. After a brief narrative summarizing and classifying the contents of the interventions, the included outcomes were categorized into each aspect of SWB (evaluative, hedonic, and eudemonic well-being, and the mental component of QOL). Finally, the characteristics of the effective interventions for increasing each aspect were summarized, and the pooled effect of interventions on SWB was investigated by a meta-analysis. Publication bias was investigated by drawing a funnel plot and conducting Egger's test. Results: From the 5,450 articles found, 39 met the inclusion criteria for the systematic review. The interventions included in this review were classified into six categories (physical activity, ergonomics, psychological, environmental, multicomponent intervention, and others). The meta-analysis from 31 studies showed that the pooled effect of included interventions on SWB was significantly positive (standardized mean difference (SMD) = 0.51; standard error (SE) = 0.10). A funnel plot showed there were extremely large or small SMDs, and Egger's test was significant. Thus, we conducted sensitivity analysis, excluding these extreme SMDs, and confirmed that the estimated pooled effect was also significantly positive. Subgroup analyses for separate types of interventions showed the effects of psychological interventions (e.g., mindfulness, cognitive behavioral based approach, and other psychological interventions) were also significantly positive. Conclusion: The current study revealed the effectiveness of interventions for increasing SWB. Specifically, psychological interventions (e.g., mindfulness, cognitive behavioral based approach, and other psychological interventions) may be useful for improving SWB.

Regional variance in the use of urine dipstick test for outpatients in Japan.

AIM: The urine dipstick is a simple diagnostic module for detecting proteinuria, haematuria and glycosuria and is favourably accepted in East Asia despite debates regarding its accuracy and target population, claiming that quantitative tests for a high-risk cohort should be more cost-effective. However, the current status of utilizing this test in these countries is not widely known due to lack of extensive data. We aimed to clarify the current nationwide and regional status of utilization of the urine dipstick test in an outpatient care setting and to determine the regional factors associated with adoption of this method. METHODS: This cross-sectional study used openly accessible data from the national claim database that included the health insurance claims data of the Japanese population in 2017. RESULTS: In total, 67 125 386 urine dipstick tests were performed compared with 1 862 700 quantitative urine protein tests and 17 544 949 urine sediment microscopy tests. Dipstick tests were employed principally for those who are >65 years old (60.3%) and, although the male population (52.5%) is generally larger, the female population is larger in age of 15 to 39 years and >85 years. Multivariate analysis with several regional parameters revealed that the test was performed more commonly in the areas that accommodate greater elderly population (P < .01). CONCLUSION: Despite a heated dispute, the urine dipstick test is performed even more frequently than the quantitative biochemical or microscopic sediment tests, especially in regions holding the larger elderly population, which suggests that the test forms a part of geriatric medical care.

Regional Variance of the Early Use of Tolvaptan for Autosomal Dominant Polycystic Kidney Disease.

Background: The development and prompt dissemination of the first drug against a particular disease can contribute to improvements in national health status and medical economy end points and are assumedly affected by socioeconomic factors that have yet to be analyzed. Tolvaptan, a vasopressin receptor 2 antagonist, was developed to treat hyponatremia, congestive heart failure, and cirrhosis ascites, although the approved indications may differ among countries. In Japan, high-dose tolvaptan tablets were approved as the first drug for autosomal dominant polycystic kidney disease (ADPKD) in 2014. This study aimed to better understand the factors that influence the total number of regional prescriptions of tolvaptan for ADPKD since its launch. Methods: The National Database of Health Insurance Claims and Specific Health Checkups of Japan Open Data was used as a national claim-based database. In each of the 47 prefectures in Japan, the total prescribed number of 30 mg tolvaptan tablets between 2015 and 2017 was examined. The parameters explaining the prescription variation among regions were then examined by correlation analysis. Results: Prescriptions for high-dose tolvaptan increased substantially 2 years after the drug's approval; however, the increase differed by approximately 21-fold between regions. Population density was positively associated with prescribed 30 mg tolvaptan tablets per 1000 population in 2015 (r=0.47, P<0.001). In addition, the increase in prescribed number of tablets per 1000 population was correlated with population density in 2016-2017 (r=0.30, P=0.04). Conclusions: This macro perspective analysis revealed an urban-rural inequity in prescriptions for the newly approved drug for ADPKD. Further studies are needed to elucidate the factors affecting the geographic variation.

Mitochondrial Damage Causes Inflammation via cGAS-STING Signaling in Acute Kidney Injury.

Acute kidney injury (AKI) is characterized by mitochondrial dysfunction and activation of the innate immune system. The cyclic GMP-AMP synthase (cGAS) stimulator of interferon genes (STING) pathway detects cytosolic DNA and induces innate immunity. Here, we investigate the role of mitochondrial damage and subsequent activation of the cGAS-STING pathway using a genetically engineered animal model of cisplatin-induced AKI and cultured tubular cells. Cisplatin induced mtDNA leakage into the cytosol-probably through BCL-2-like protein 4 (BAX) pores in the mitochondrial outer membrane-in tubules, with subsequent activation of the cGAS-STING pathway, thereby triggering inflammation and AKI progression, which is improved in STING-deficient mice. STING knockdown in cultured tubular cells ameliorates inflammatory responses induced by cisplatin. mtDNA depletion and repletion studies support tubular inflammatory responses via the cGAS-STING signal activation by cytosolic mtDNA. Therefore, we conclude that mitochondrial dysfunction and subsequent activation of the mtDNA-cGAS-STING pathway is a critical regulator of kidney injury.

Association between psychosocial factors at work and health outcomes after retirement: a protocol for a systematic review and meta-analysis.

INTRODUCTION: The world's population is rapidly ageing, and health among older people is thus an important issue. Several previous studies have reported an association between adverse psychosocial factors at work before retirement and postretirement health. The objective of this systematic review and meta-analysis is to examine the association between psychosocial factors at work and health outcomes after retirement, based on a synthesis of well-designed prospective studies. METHODS AND ANALYSIS: The participants, exposures, comparisons and outcomes of the studies in this systematic review and meta-analysis are defined as follows: (P) people who have retired from their job, (E) presence of adverse psychosocial factors at work before retirement, (C) absence of adverse psychosocial factors at work before retirement and (O) any physical and mental health outcomes after retirement. Published studies were searched using the following electronic databases: MEDLINE, EMBASE, PsycINFO, PsycARTICLES and Japan Medical Abstracts Society. The included studies will be statistically synthesised in a meta-analysis to estimate pooled coefficients and 95% CIs. The quality of each included study will be assessed using the Risk Of Bias In Non-randomised Studies-of Interventions. For the assessment of meta-bias, publication bias will be assessed by using Egger's test, as well as visually on a funnel plot. Heterogeneity will be assessed using the χ² test with Cochran's Q statistic and I2. ETHICS AND DISSEMINATION: Results and findings will be submitted and published in a scientific peer-reviewed journal and will be disseminated broadly to researchers and policy-makers interested in the translatability of scientific evidence into good practices. PROSPERO REGISTRATION NUMBER: CRD42018099043.

Regional variance in patterns of prescriptions for chronic kidney disease in Japan.

BACKGROUND: This study aims to describe the regional variance in prescriptions for chronic kidney disease (CKD) medications and to analyze regional characteristics to identify the sources of these differences by utilizing the National Database of Health Insurance Claims, which provides more than 95% of nationwide claim information for Japan. METHODS: Data regarding the total claimed amount for phosphate binders (PBs), erythropoiesis-stimulating agents (ESAs), carbonaceous adsorbents, and potassium-lowering agents in fiscal year 2015 were obtained. Correlation coefficients were calculated for the claimed amount of these drugs per CKD patient and social and medical variables, including the percentage of the population aged ≥ 65 years and the numbers of hospital beds and certified nephrologists. Subsequent multiple regression analysis was performed using explanatory factors affecting the amount of PB or ESA prescriptions per CKD patient. RESULTS: The total claimed amounts were 585,485,115 for PBs and 2,373,777 for ESAs. Variations in the claimed amount per CKD patient among 47 prefectures were 4.9-, 6.1-, 6.6-, and 6.0-fold for PBs, ESAs, carbonaceous adsorbents and potassium-lowering agents, respectively. The number of nephrologists per CKD patient was positively correlated with the prescribed amount for PBs and ESAs per CKD patient, and independently associated with the prescribed amount also in regression analysis. CONCLUSION: Substantial regional variation in CKD-related drug prescriptions exists even within a uniform health care system. The number of certified nephrologists was associated with the prescribed amount for PBs and ESAs. Further studies are needed to clarify whether geographic distribution of certified nephrologist may affect clinical practice pattern.

Psychosocial factors at work and inflammatory markers: protocol for a systematic review and meta-analysis.

INTRODUCTION: Chronic inflammation may be a mediator for the development of cardiovascular disease (CVD), metabolic diseases and psychotic and neurodegenerative disorders. Meta-analytic associations between work-related psychosocial factors and inflammatory markers have shown that work-related psychosocial factors could affect the flexibility and balance of the immune system. However, few systematic reviews or meta-analyses have investigated the association between work-related psychosocial factors and inflammatory markers. Based on prospective studies, the present investigation will conduct a comprehensive systematic review and meta-analysis of the association between work-related psychosocial factors and inflammatory markers. METHODS AND ANALYSIS: The systematic review and meta-analysis will include published studies identified from electronic databases (PubMed, EMBASE, PsycINFO, PsycARTICLES, Web of Science and Japan Medical Abstracts Society) according to recommendations of the Meta-analysis of Observational Studies in Epidemiology guideline. Inclusion criteria are studies that: examined associations between work-related psychosocial factors and increased inflammatory markers; used longitudinal or prospective cohort designs; were conducted among workers; provided sufficient data for calculating ORs or relative risk with 95% CIs; were published as original articles in English or Japanese; and were published up to the end of 2017. Study selection, data extraction, quality assessment and statistical syntheses will be conducted by 14 investigators. Any inconsistencies or disagreements will be resolved through discussion. The quality of studies will be evaluated using the Risk of Bias Assessment Tool for Non-randomized Studies. ETHICS AND DISSEMINATION: The investigation study will be based on published studies, so ethics approval is not required. The results of this study will be submitted for publication in a scientific peer-reviewed journal. The findings may be useful for assessing risk factors for increased inflammatory markers in the workplace and determining future approaches for preventing CVD, metabolic diseases and psychotic and neurodegenerative disorders. PROSPERO REGISTRATION NUMBER: CRD42018081553.