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Abstract Background A recent database study and meta-analysis reported that adjunctive glucocorticoid therapy reduces mortality in patients with non-human immunodeficiency virus-associated (non-HIV) Pneumocystis jirovecii pneumonia (PCP), having hypoxemia. However, the optimal glucocorticoid dose remains unclear. Our study aimed to evaluate the effectiveness of pulse methylprednisolone compared with mild-to-moderate steroid doses in patients with non-HIV PCP. Methods This multicentre retrospective cohort study included adults with non-HIV PCP receiving adjunctive steroids at three Japanese tertiary care hospitals from June 2006 to March 2021. Patients were categorised into pulse methylprednisolone and mild-to-moderate dose groups. Pulse methylprednisolone involved an initial intravenous infusion of 500–1000 mg methylprednisolone daily, while the mild-to-moderate dose was lower. Primary and secondary outcomes were 30-day and 180-day mortality from treatment initiation. Patient characteristics were adjusted using propensity score analysis with overlap weighting. Subgroup analysis focused on patients with respiratory failure. Results The study included 139 patients with non-HIV PCP: 55 in the pulse methylprednisolone group and 84 in the mild-to-moderate dose group. After adjusting for patient background, 30-day mortality (14.2% vs. 15.5%, P = 0.850) and 180-day mortality (33.5% vs. 27.3%, P = 0.516) did not differ significantly between groups. Subgroup analysis revealed no significant associations among patients with respiratory failure. Conclusions After adjusting for patient characteristics, no difference in prognosis was observed between pulse methylprednisolone and mild-to-moderate dose groups in patients with non-HIV PCP. A mild-to-moderate dose of adjunctive corticosteroid may suffice for treating non-HIV PCP.

Introduction Janus kinase (JAK) inhibitors are an important therapeutic option in the treatment of rheumatoid arthritis, but increase the risk of developing herpes zoster. Although a dry recombinant zoster vaccine (RZV) that can be used under immunosuppressive conditions has recently been developed, its optimal use and appropriate timing in patients scheduled to start JAK inhibitors is still unclear. The present study is designed to clarify the appropriate timing of JAK inhibitor initiation to measure varicella zoster virus (VZV)-specific IgG titers and VZV-specific T cell response in patients with rheumatoid arthritis who start tofacitinib at the first RZV vaccination or at the second one.Methods and analysis STOP HZ (Effectiveness and SafeTy Of Prophylactic Recombinant Herpes Zoster Virus Vaccination for Rheumatoid Arthritis Patients with Tofacitinib Treatment) study is a multicentre, open-label, randomised, comparative study in patients with rheumatoid arthritis who are scheduled to start tofacitinib. This study enrols 60 study subjects in 12 sites. Enrolled subjects receive RZV two times on day 1 and week 8 and initiate tofacitinib 5 mg two times a day at the time of their first RZV (day 1, group A) or second RZV (week 8, group B) based on randomisation. The random assignment is performed centrally in a 1:1 ratio. Patients in Group B continue the same treatment until the start of tofacitinib treatment. Primary endpoint is VZV-specific IgG antibody titers at week 12 compared with those at baseline in each group. Secondary endpoints include comparison of VZV-specific IgG antibody between the groups, changes in disease activity of rheumatoid arthritis, VZV-specific T cell response and adverse events.Ethics and dissemination The study has been approved by the Certified Review Board of Keio (No. 2022008), and conforms to the Declaration of Helsinki and good clinical practice guidelines. Written informed consent is obtained from participants prior to enrolment. The results of this study are planned to be submitted for publishment in relevant peer-review journals.Trial registration number jRCTs031230329.

Introduction Although conventional cigarette smoking has been linked to an increased risk of hearing loss, the association between heated tobacco products (HTPs) and hearing loss is unknown. The objective of this study was to investigate the association between cigarette and HTP use and hearing loss. Methods This cross-sectional study examined the data of 7769 employees from five companies (Study I) and 34404 employees from a large company (Study II), all participants in the Japan Epidemiology Collaboration on Occupational Health Study. The participants were categorized into five groups based on their selfreported tobacco use: never smokers, former smokers, exclusive cigarette smokers, exclusive users of HTPs, and those who used both cigarettes and HTPs. Hearing levels were measured using pure-tone audiometry at 1 and 4 kHz frequencies. Separate analyses were carried out for each study, and the results were then combined using fixed-effect models to pool the estimates. Results The analysis included 42173 participants, with a prevalence of 12.9% for exclusive cigarette smoking, 9.8% for exclusive HTP use, and 5.5% for dual use. The pooled adjusted odds ratios with 95% confidence intervals for unilateral hearing loss at 4 kHz were 1.21 (95% CI: 1.10–1.33) for former smokers, 1.83 (95% CI: 1.64–2.05) for exclusive cigarette smokers,1.46 (95% CI: 1.28–1.67) for exclusive HTP users, and 1.66 (95% CI: 1.41–1.96) for dual users, compared to never smokers. Additionally, the adjusted odds ratios for hearing loss at 4 kHz among exclusive cigarette smokers, exclusive HTP users, and dual users increased with the intensity of cigarette/HTP consumption (all p for trend

Background: Diabetes and prediabetes have been linked with morbidity or mortality from cardiovascular disease, cancer, or other physical disorders among working-age populations, but less is known about outcomes directly related to labor loss (eg, Tlong-term sickness absence [LTSA] or pre-retirement death due to physical disorders). This prospective study aimed to examine the association of diabetes and prediabetes with the risk of a composite outcome of LTSA and pre-retirement death due to physical disorders. The present study also examined the associations of severe outcomes (LTSA or death) due to specific physical disorders or injuries/external causes in relation to diabetes and prediabetes. Methods: Data were derived from the Japan Epidemiology Collaboration on Occupational Health study. A total of 60,519 workers from 12 companies were followed for 8 years. Diabetes and prediabetes were defined based on the American Diabetes Association criteria. A Cox proportional hazards regression model was used to examine the association between diabetes/prediabetes and severe outcomes due to physical disorders or injuries/external causes. Results: The adjusted hazard ratios of severe outcomes due to all physical disorders were 1.22 (95% confidence interval [CI], 1.02–1.45) and 2.32 (95% CI, 2.04–2.64) for prediabetes and diabetes, respectively. In cause-specific analyses, an increased risk was observed for severe outcomes due to cancers, cardiovascular diseases, diseases of the musculoskeletal system, and injuries/external causes in relation to either or both diabetes and prediabetes. Conclusion: Diabetes and prediabetes were associated with an increased risk of severe outcomes due to physical disorders or injuries/external causes among Japanese workers.

Abstract Background Living alone has been positively associated with the prevalence of depressive symptoms. We examined how a combination of living alone and pet ownership relates to depressive symptoms. Methods As part of the Japan Epidemiology Collaboration on Occupational Health Study, we conducted a survey on health-related lifestyles, including living arrangements and pet ownership, among 12,763 employees of five companies in 2018–2021. Depressive symptoms were assessed using the 11-item Center for Epidemiological Studies-Depression Scale (cutoff score ≥ 9). A Poisson regression model with a robust variance estimator was used to calculate prevalence ratio and 95% confidence interval (CI) while adjusting for covariates. Results Among the participants, 30.9% were depressed, 17.7% had pets, and 29.1% lived alone. Compared to individuals living with others but not with a pet, those living alone and not with a pet had a 1.17 times higher prevalence ratio of depressive symptoms (95% CI: 1.08-1.26). The corresponding figures were 1.03 (95% CI: 0.95-1.11) for those living with others and pet(s) and 1.42 (95% CI: 1.18-1.69) for those living alone but with pet(s). Conclusion Living alone was significantly associated with a higher prevalence of depressive symptoms. The association was rather stronger among individuals with vs. without pets. Pet ownership may not be associated with decreased depressive symptoms.

Abstract Background Metabolic syndrome (MetS) is associated with cancer risk; however, little is known regarding its relationship with the risk of cancer-related premature death and long-term sick leave (LTSL), which can lead to a substantial loss in working years. The present study aimed to quantify the all-site and site-specific associations between MetS and the risk of severe cancer events (a composite outcome of LTSL and mortality due to cancer) in a large working population in Japan. Methods We recruited 70,875 workers (59,950 men and 10,925 women), aged 20–59 years, who attended health check-ups in 2011 (10 companies) and 2014 (2 companies). All workers underwent follow up for severe cancer events until March 31, 2020. MetS was defined in accordance with the Joint Interim Statement. Cox regression models were used to quantify the association between baseline MetS and severe cancer events. Results During 427,379 person-years of follow-up, 523 participants experienced the outcome consisting of 493 LTSLs of which 124 eventually resulted in death, and 30 deaths without taking LTSL. The adjusted hazard ratios (HR) (95% confidence intervals [CI]) for composite severe events due to all-site, obesity-related, and non-obesity-related cancer among those with vs. without MetS were 1.26 (1.03, 1.55), 1.37 (1.04, 1.82), and 1.15 (0.84, 1.56), respectively. In cancer site-specific analyses, MetS was associated with an increased risk of severe events due to pancreatic cancer (HR, 2.06; 95% CI, 0.99–4.26). When mortality was treated solely as the endpoint, the association was significant for all-site (HR, 1.58; 95% CI, 1.10–2.26), and obesity-related (HR, 1.59; 95% CI, 1.00–2.54) cancer. Additionally, a greater number of MetS components was associated with a greater risk of both severe cancer events and cancer-related mortality (P trend

Background: Metabolic syndrome (MetS) has been associated with various chronic diseases that may lead to long-term sickness absence (LTSA), but there is lacking information on the direct association between MetS and LTSA. The present study aimed to investigate the all-cause and cause-specific associations between MetS and the risk of medically certified LTSA among Japanese workers. Methods: We recruited 67,403 workers (57,276 men and 10,127 women), aged 20–59 years from 13 companies in Japan during their health check-ups in 2011 (11 companies) and 2014 (2 companies), and we followed them for LTSA events (≥30 consecutive days) until March 31, 2020. MetS was defined according to the Joint Interim Statement. A Cox proportional hazards regression model was used to estimate hazard ratios (HRs) and its 95% confidence intervals (CIs) for LTSA associated with MetS and its components. Results: During 408,324 person-years of follow-up, 2,915 workers experienced LTSA. The adjusted HR for all-cause LTSA was 1.54 (95% CI, 1.41–1.68) among those with MetS compared to those without MetS. In cause-specific analysis, HRs associated with MetS significantly increased for LTSA due to overall physical disorders (1.76); cardiovascular diseases (3.16); diseases of the musculoskeletal system and connective tissue (2.01); cancers (1.24); obesity-related cancers (1.35); mental, behavioral, and neurodevelopmental disorders (1.28); reaction to severe stress and adjustment disorders (1.46); and external causes (1.46). The number of MetS components were also significantly associated with increased LTSA risk. Conclusion: MetS was associated with an increase in the risk of LTSA due to various diseases among Japanese workers.

Abstract Introduction To evaluate patient–physician communication and patients’ understanding of treatment goals in rheumatoid arthritis (RA). Methods A cross-sectional online survey of patients with RA and physicians treating RA was conducted between 16 and 30 June 2021. Participants were asked to rate the importance of 17 goals on a 6-point Likert scale, and mean scores were compared between patients and physicians by the Wilcoxon rank sum test. Patients’ satisfaction with physician communication and their understanding of treatment goals were also assessed. Results The responses of 502 patients and 216 physicians were analyzed. The most common patient age group was 50–59 years (28.5%), and the mean disease duration was 10.3 years. Physicians had a mean of 19.2 years of treatment experience and were treating a mean of 44.3 patients. Among the 17 goals assessed, patients placed significantly more importance on drug tapering or discontinuation as short-term goals (3–6 months) and on performing basic activities of daily living, being able to engage in daily tasks, achieving and maintaining remission, maintaining better laboratory values, and drug tapering or discontinuation as long-term goals (5–10 years; all adjusted p

Abstract We aimed to assess the association between heated tobacco product (HTP) use and high-density lipoprotein cholesterol (HDL-C) concentration. Our study included 12,268 workers from five companies (Study I) and 36,503 workers from another large company (Study II). Participants were categorized into five groups: never smokers, past smokers, exclusive HTP users, dual users of cigarettes and HTPs, and exclusive cigarette smokers. We analyzed the data of Studies I and II separately and then pooled these estimates using a fixed-effect model. Of the 48,771 participants, 9.3% were exclusive HTP users, and 6.0% were dual users. Exclusive HTP users had modestly but significantly lower concentrations of HDL-C than never smokers, with the pooled mean difference being − 1.1 (95% CI − 1.5 to − 0.6) mg/dL. Dual users showed a further reduction (mean difference − 3.7 (− 4.2 to − 3.2) mg/dL), which was comparable to that of exclusive cigarette smokers versus never smokers (mean difference − 4.3 (− 4.7 to − 3.9) mg/dL). The pooled odds ratios (95% CIs) of having low HDL-C (

Background: While it is essential to understand how long is sufficient for return-to-work when designing paid sick-leave systems, little attempt has been done to collect cause-specific information on when and how many of sickness absentees returned to work, became unemployed, or passed away. Methods: We studied the first sick-leave episode of ≥30 consecutive days in those ≤55 years of age during 2012–2013 among employees of 11 Japanese private companies (n = 1,209), which were followed until 2017. Overall and disease-specific cumulative incidences of return-to-work, resignations, and deaths were estimated using competing risk analysis. Results: During the 3.5-year period (follow-up rate: 99.9%), 1,014 returned to work, 167 became unemployed, and 27 died. Overall, return-to-work occurred within 1 year in 74.9% of all absentees and in 89.3% of those who successfully returned to work. Resignation occurred within 1 year in 8.7% of all absentees and in 62.9% of all subjects who resigned. According to ICD-10 chapters, the cumulative incidence of return-to-work ranged from 82.1% for mental disorders (F00–F99) to 95.3% for circulatory diseases (I00–I99). The cumulative incidence of return-to-work due to mental disorders ranged from 66.7% in schizophrenia (F20) to 95.8% in bipolar affective disorders (F31). Death was rarely observed except for cases of neoplasms (C00–D48), of which the cumulative incidence of death reached 14.2% by 1.5 years. Conclusion: Return-to-work and resignations occurred commonly within 1 year of sick leave among long-term sickness absentees in the Japanese private companies. Our findings may assist occupational physicians and employers in developing effective social protection schemes.

Background: Although previous research has focused on the association between long working hours and several mental health outcomes, little is known about the association in relation to mental health-related sickness absence, which is a measure of productive loss. We aimed to investigate the association between overtime work and the incidence of long-term sickness absence (LTSA) due to mental disorders. Methods: Data came from the Japan Epidemiology Collaboration on Occupational Health Study (J-ECOH). A total of 47,422 subjects were followed-up in the period between April 2012 and March 2017. Information on LTSA was obtained via a study-specific registry. Baseline information was obtained at an annual health checkup in 2011; overtime working hours were categorized into

The coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 has led to rapid progress in vaccine development to prevent the spread of the disease. Although COVID-19 vaccines have excellent effectiveness in reducing morbidity and disease severity with minor adverse reactions, some patients develop late hypersensitivity events as autoimmune reactions such as rheumatoid arthritis, lupus nephritis, and vasculitis following COVID-19 vaccination. Herein, we describe a case of pneumonitis following COVID-19 mRNA vaccination in a patient with rheumatoid arthritis, which resolved spontaneously.