Factors Associated with Refraining from Health Checkups during the COVID-19 Pandemic in Japan.

This study aimed to determine the characteristics of people who refrained from having regular checkups due to the spread of the novel coronavirus 2019 (COVID-19) infection and the factors associated with this behavior. We conducted a nationwide internet survey of 4593 males and females aged 20-69 in Japan regarding their health checkups from April 2020 to March 2021, when COVID-19 was widespread. Individuals who received checkups during this time were "the receiving group"; those who did not were "the refraining group". Personal attributes, responses to a health questionnaire and other items were used to compare the groups. The analysis showed that males over 53 refrained from having health checkups compared to those younger. On the other hand, males with higher personal incomes who never skipped breakfast received health checkups. Females with children under 18 years were less likely than those without to receive health checkups. For males, the characteristic factors were economic and health awareness and literacy. Females were less aware of medical checkups. Moreover, they demonstrated an inability to maintain an everyday rhythm. No factors were common to males and females, indicating the need to consider separate strategies for encouraging males and females to obtain annual health checkups.

Five cluster classifications of long COVID and their background factors: A cross-sectional study in Japan.

PURPOSE: The long-term symptoms of coronavirus disease 2019 (COVID-19), i.e., long COVID, have drawn research attention. Evaluating its subjective symptoms is difficult, and no established pathophysiology or treatment exists. Although there are several reports of long COVID classifications, there are no reports comparing classifications that include patient characteristics, such as autonomic dysfunction and work status. We aimed to classify patients into clusters based on their subjective symptoms during their first outpatient visit and evaluate their background for these clusters. METHODS: Included patients visited our outpatient clinic between January 18, 2021, and May 30, 2022. They were aged ≥ 15 years and confirmed to have SARS-CoV-2 infection and residual symptoms lasting at least 2 months post-infection. Patients were evaluated using a 3-point scale for 23 symptoms and classified into five clusters (1. fatigue only; 2. fatigue, dyspnea, chest pain, palpitations, and forgetfulness; 3. fatigue, headache, insomnia, anxiety, motivation loss, low mood, and forgetfulness; 4. hair loss; and 5. taste and smell disorders) using CLUSTER. For continuous variables, each cluster was compared using the Kruskal-Wallis test. Multiple comparison tests were performed using the Dunn's test for significant results. For nominal variables, a Chi-square test was performed; for significant results, a residual analysis was conducted with the adjusted residuals. RESULTS: Compared to patients in other cluster categories, those in cluster categories 2 and 3 had higher proportions of autonomic nervous system disorders and leaves of absence, respectively. CONCLUSIONS: Long COVID cluster classification provided an overall assessment of COVID-19. Different treatment strategies must be used based on physical and psychiatric symptoms and employment factors.

The levels of serum soluble CD86 are correlated with the expression of CD86 variant 3 gene and are prognostic indicators in patients with myeloma.

We previously showed that cell-surface CD86 expressed on multiple myeloma (MM) cells contributed to not only tumor growth but also antitumor cytotoxic T-lymphocyte responses mediated by induction of IL-10-producing CD4+ T cells. The soluble form of CD86 (sCD86) was also detected in serum from patients with MM. Thus, to determine whether sCD86 levels are a useful prognostic factor, we investigated the association of serum sCD86 levels with disease progression and prognosis in 103 newly diagnosed patients with MM. Serum sCD86 was detected in 71% of the patients with MM but was only rarely detected in patients with monoclonal gammopathy of undetermined significance and healthy controls, and the level was significantly increased in patients with advanced-stage MM. When we examined differences in clinical characteristics according to the level of serum sCD86, those in the high (≥2.18 ng/mL, n = 38) group exhibited more aggressive clinical characteristics, with shorter overall survival times compared with those in the low (<2.18 ng/mL, n = 65) group. On the other hand, it was difficult to stratify the patients with MM into different risk groups based on the expression levels of cell-surface CD86. The levels of serum sCD86 were significantly correlated with the expression levels of the messenger RNA (mRNA) transcripts of CD86 variant 3, which lack exon 6, resulting in a truncated transmembrane region, and its variant transcripts were upregulated in the high group. Thus, our findings suggest that sCD86 can be easily measured in peripheral blood samples and is a useful prognostic marker in patients with MM.

Negative E-cadherin expression on bone marrow myeloma cell membranes is associated with extramedullary disease.

Background: The loss of E-cadherin expression and the induction of N-cadherin are known as hallmarks of the epithelial-to-mesenchymal transition, an essential initial step in the process of metastasis in solid tumors. Although several studies have reported expressions of these cadherins in patients with multiple myeloma (MM), their clinical significance is unknown as MM cells are non-epithelial. Methods: In this study, we examined the expression of E- and N-cadherins by immunohistochemistry using bone marrow (BM) biopsy specimens from 31 newly diagnosed MM patients and in subsequent biopsy specimens from six of these. Results: Negative E-cadherin expression on BM myeloma cell membranes was significantly associated with the presence of soft-tissue masses arising from bone lesions and breaking through the cortical bone, referred to as extramedullary disease (EMD). Conclusions: Given the aggressive nature of EMD, our study suggests that screening for E-cadherin using BM immunohistochemistry is one measure that could predict the development of EMD in patients with MM.

Health state utilities of patients with hepatitis B and C and hepatitis-related conditions in Japan.

Health state utilities are global measurements of quality of life and have been used to evaluate health outcomes for the cost-utility analysis. This study aimed to estimate the health state utilities of patients with hepatitis B (HB), hepatitis C (HC), and hepatitis-related diseases in Japan. We distributed a self-administered questionnaire, including the EuroQol 5-Dimension 5-Level (EQ-5D-5L), to 9,952 outpatients with several clinical conditions caused by HB or HC virus infection (such as asymptomatic chronic hepatitis, chronic hepatitis, compensated cirrhosis, and decompensated cirrhosis) and estimated the condition-specific utilities of patients with HB or HC. In patients with more severe conditions (patients with acute hepatitis, fulminant hepatitis, and hepatocellular carcinoma and patients undergoing post-liver transplantation), the utilities of these severe conditions were estimated by three hepatitis experts using the EQ-5D-5L. The means of the utilities for acute hepatitis, fulminant hepatitis, asymptomatic chronic hepatitis, chronic hepatitis, compensated cirrhosis, compensated cirrhosis, hepatocellular carcinoma stage I/II, hepatocellular carcinoma stage III/IV, and post-liver transplantation were 0.529, - 0.111, 0.904, 0.868, 0.845, 0.722, 0,675, 0,428, and 0.651 and 0.876, 0.821, 0.737, 0.671, 0.675, 0.428, and 0.651 in HB and HC, respectively. To the best of our knowledge, this is the first study that comprehensively assessed the health state utilities of patients with HB, HC and hepatitis-related conditions from a nationwide survey in Japan using the EQ-5D-5L.

Working conditions contribute to fertility-related quality of life: a cross-sectional study in Japan.

RESEARCH QUESTION: Is there an association between employment conditions and fertility-related quality of life among women undergoing fertility care? DESIGN: The study was a cross-sectional survey of 721 women in Japan recruited via an online social research panel. Participants included women aged 25-44 years with paid employment who were undergoing fertility diagnosis or treatment. They completed online questionnaires to assess fertility quality of life (FertiQoL) and job stress based on the demand-control-support model (Brief Job Stress Questionnaire). Information was also collected on individual and partner employment conditions (e.g. working hours per week, access to time off) and partner support of fertility treatment. RESULTS: The mean FertiQoL scores were low, ranging from 42 (emotional) to 65 (relational). A multivariable linear regression model showed that the total FertiQoL score was significantly associated with several work-related variables, including the participants' self-employment status (ß = 0.11), job demand (ß = -0.18), co-worker support (ß = 0.14) and access to time off (ß = 0.22), as well as their partner's access to time off (ß = 0.11), number of working hours (ß = -0.11) and level of cooperation (ß = 0.18), after adjusting for clinical and socioeconomic factors, including age (ß = 0.10), diagnosis of male infertility (ß = -0.07), long duration of treatment (ß = -0.12) and frequent clinic visits (ß = -0.10) (all Ps < 0.05, adjusted R2 = 0.27). CONCLUSIONS: Fertility-related quality of life is significantly associated with certain employment conditions among both women and their partners. Easy access to time off, lighter workloads and supportive co-workers could contribute to higher fertility-related quality of life by helping employees effectively manage their work and fertility treatments.

Prevalence of COVID-19 and the Continued Citizen-Based Control in Japan.

Since an outbreak of COVID-19 was detected among the crew and passengers of the Diamond Princess cruise ship in early 2020, the total number of cases of SARS-CoV-2 has surpassed 440,000 in Japan. However, that number remains small compared with other countries, such as the United States, a few European countries, and China. Despite the Japanese government not imposing a lockdown or implementing large-scale testing at the municipal level, the country has managed to contain the smaller outbreaks. To avoid infection, it is important to wear a face mask, wash one's hands, and observe social distancing. In addition, we focus on the clinical laboratory testing performed using the latest technology to detect SARS-CoV-2 RNA in a hospital in Yokohama, Japan. Large-scale testing of viral RNA would be useful for detecting asymptomatic virus carriers as is done in other countries, and could be carried out as a future measure for controlling COVID-19.

SLAMF3-Mediated Signaling via ERK Pathway Activation Promotes Aggressive Phenotypic Behaviors in Multiple Myeloma.

The signaling lymphocytic activation molecule family 3 (SLAMF3) is a member of the immunoglobulin superfamily expressed on T, B, and natural killer cells and modulates the activation and cytotoxicity of these cells. SLAMF3 is also expressed on plasma cells from patients with multiple myeloma (MM), although its role in MM pathogenesis remains unclear. This study found that SLAMF3 is highly and constitutively expressed on MM cells regardless of disease stage and that SLAMF3 knockdown/knockout suppresses proliferative potential and increases drug-induced apoptosis with decreased levels of phosphorylated ERK protein in MM cells. SLAMF3-overexpressing MM cells promote aggressive myeloma behavior in comparison with cytoplasmic domain-truncated SLAMF3 (ΔSLAMF3) cells. SLAMF3 interacts directly with adaptor proteins SH2 domain-containing phosphatase 2 (SHP2) and growth factor receptor bound 2 (GRB2), which also interact with each other. SLAMF3 knockdown, knockout, ΔSLAMF3, and SHP2 inhibitor-treated MM cells decreased phosphorylated ERK protein levels. Finally, serum soluble SLAMF3 (sSLAMF3) levels were markedly increased in advanced MM. Patients with high levels of sSLAMF3 progressed to the advanced stage significantly more often and had shorter progression-free survival times than those with low levels. This study revealed that SLAMF3 molecules consistently expressed on MM cells transmit MAPK/ERK signals mediated via the complex of SHP2 and GRB2 by self-ligand interaction between MM cells and induce a high malignant potential in MM. Furthermore, high levels of serum sSLAMF3 may reflect MM disease progression and be a useful prognostic factor. IMPLICATIONS: SLAMF3 may be a new therapeutic target for immunotherapy and novel agents such as small-molecule inhibitors.

Domestic work stress and self-rated psychological health among women: a cross-sectional study in Japan.

BACKGROUND: Despite the huge burden of domestic work on women in Japan, its effects on their health have been poorly investigated. We aimed to assess the association between domestic work stress and self-rated psychological health among women. METHODS: We conducted a cross-sectional survey using an online social research panel in February 2018. Participants were 2,000 women with paid work (the "workers" group) and 1,000 women without paid work (the "homemakers" group), aged between 25 and 59 years old and living with a partner. Self-rated psychological health (Mental Health and Vitality scales of the Japanese SF-36), occupational and domestic work stress (the Brief Job Stress Questionnaire), the 10-item Work-Family Conflict Scale, and sociodemographic factors were assessed. RESULTS: The workers had lower domestic job control and higher support from a partner and their parents than the homemakers (p < 0.001), whereas domestic job demand and psychological health were similar between the groups. After adjustment for the covariates using multiple linear regression models, better psychological health was significantly associated with lower domestic job demand, higher domestic job control, and having a young child in both groups. In addition, work-family conflicts and occupational job stress among the workers and caregiving among the homemakers showed negative associations with psychological health. CONCLUSION: Self-rated psychological health in women was associated with domestic work stress regardless of employment status. To promote women's health, we need to take into account the effects of domestic work, work-family conflicts, and social support from families, as well as occupational factors.

Clinical impact of serum soluble SLAMF7 in multiple myeloma.

The signaling lymphocytic activation molecule family (SLAMF7; also known as CS1 or CD319) is highly expressed on plasma cells from multiple myeloma (MM) as well as natural killer (NK) cells and is a well-known therapeutic target of elotuzumab. The objective of this study was to evaluate the clinical significance of serum soluble SLAMF7 (sSLAMF7) levels in patients with MM (n=103) and furthermore the impact of sSLMF7 on the antitumor activity of anti-SLAMF7 antibody. Thirty-one percent of MM patients, but not patients with monoclonal gammopathy of undetermined significance and healthy controls, had detectable levels of serum sSLAMF7, which were significantly increased in advanced MM patients. Further, MM in sSLAMF7-postive patients exhibited aggressive clinical characteristics with shorter progression-free survival times in comparison with sSLAMF7-negative patients. In responders to MM therapy, the levels of sSLAMF7 were undetectable or decreased compared with those before treatment. In addition, the anti-SLAMF7 antibody-mediated antibody-dependent cellular cytotoxicity of NK cells against MM cell lines was inhibited by recombinant SLAMF7 protein. Thus, our findings suggest that high concentrations of sSLAMF7, which could transiently suppress the therapeutic effects of elotuzumab, may be a useful indicator of disease progression in MM patients.

Adaptation of the European Commission-recommended user testing method to patient medication information leaflets in Japan.

BACKGROUND: The safe use of drugs relies on providing accurate drug information to patients. In Japan, patient leaflets called Drug Guide for Patients are officially available; however, their utility has never been verified. This is the first attempt to improve Drug Guide for Patients via user testing in Japan. PURPOSE: To test and improve communication of drug information to minimize risk for patients via user testing of the current and revised versions of Drug Guide for Patients, and to demonstrate that this method is effective for improving Drug Guide for Patients in Japan. METHOD: We prepared current and revised versions of the Drug Guide for Patients and performed user testing via semi-structured interviews with consumers to compare these versions for two guides for Mercazole and Strattera. We evenly divided 54 participants into two groups with similar distributions of sex, age, and literacy level to test the differing versions of the Mercazole guide. Another group of 30 participants were divided evenly to test the versions of the Strattera guide. After completing user testing, the participants evaluated both guides in terms of amount of information, readability, usefulness of information, and layout and appearance. Participants were also asked for their opinions on the leaflets. RESULTS: Response rates were 100% for both Mercazole and Strattera. The revised versions of both Guides were superior or equal to the current versions in terms of accessibility and understandability. The revised version of the Mercazole guide showed better ratings for readability, usefulness of information, and layout (p<0.01) than did the current version, while that for Strattera showed superior readability and layout (p<0.01). CONCLUSION: User testing was effective for evaluating the utility of Drug Guide for Patients. Additionally, the revised version had superior accessibility and understandability.

Cost-Effectiveness Analysis of Percutaneous Vertebroplasty for Osteoporotic Compression Fractures.

STUDY DESIGN: Single-center, single-arm, prospective time-series study. OBJECTIVE: To assess the cost-effectiveness and improvement in quality of life (QOL) of percutaneous vertebroplasty (PVP). SUMMARY OF BACKGROUND DATA: PVP is known to relieve back pain and increase QOL for osteoporotic compression fractures. However, the economic value of PVP has never been evaluated in Japan where universal health care system is adopted. METHODS: We prospectively followed up 163 patients with acute vertebral osteoporotic compression fractures, 44 males aged 76.4±6.0 years and 119 females aged 76.8±7.1 years, who underwent PVP. To measure health-related QOL and pain during 52 weeks observation, we used the European Quality of Life-5 Dimensions (EQ-5D), the Rolland-Morris Disability Questionnaire (RMD), the 8-item Short-Form health survey (SF-8), and visual analogue scale (VAS). Quality-adjusted life years (QALY) were calculated using the change of health utility of EQ-5D. The direct medical cost was calculated by accounting system of the hospital and Japanese health insurance system. Cost-effectiveness was analyzed using incremental cost-effectiveness ratio (ICER): Δ medical cost/Δ QALY. RESULTS: After PVP, improvement in EQ-5D, RMD, SF-8, and VAS scores were observed. The gain of QALY until 52 weeks was 0.162. The estimated lifetime gain of QALY reached 1.421. The direct medical cost for PVP was ¥286,740 (about 3061 US dollars). Cost-effectiveness analysis using ICER showed that lifetime medical cost for a gain of 1 QALY was ¥201,748 (about 2154 US dollars). Correlations between changes in EQ-5D scores and other parameters such as RMD, SF-8, and VAS were observed during most of the study period, which might support the reliability and applicability to measure health utilities by EQ-5D for osteoporotic compression fractures in Japan as well. CONCLUSIONS: PVP may improve QOL and ameliorate pain for acute osteoporotic compression fractures and be cost-effective in Japan.

Fertility knowledge and the timing of first childbearing: a cross-sectional study in Japan.

Although fertility educational initiatives have increased in developed countries to prevent infertility and to broaden fertility choices, the relationship between knowledge and behaviour is still poorly understood. In order to investigate the association between fertility knowledge and timing of childbearing, we investigated male and female participants between 35 and 44 years of age who had children (n = 640) from an online survey conducted in Japan in 2013. The age at which participants actually gave birth to or fathered their first child was compared between those who were aware for at least a decade of age-related decline in female fertility (hereinafter, those with past fertility knowledge) and those without. Age at first birth was significantly younger and more narrowly distributed among women with past fertility knowledge than among those without: 28.2 ± 3.4 vs. 29.8 ± 4.6 (mean ± SD). A multivariate linear regression analysis showed that women with past fertility knowledge gave birth to their first child 2.34 [95% confidence interval (CI): 1.09-3.59] years earlier compared to those without such knowledge. No significant relation existed among men. Being informed in young adulthood about the facts of fertility might be related to starting a family at an earlier age, although further longitudinal evaluation will be necessary.

Incidence and clinical background of hepatitis B virus reactivation in multiple myeloma in novel agents' era.

There are some reports regarding hepatitis B virus (HBV) reactivation in patients with myeloma who are HBV carriers or who have had a resolved HBV infection, and there is no standard prophylaxis strategy for these patients. We performed a retrospective multicenter study to determine the incidence and characteristics of HBV reactivation in patients with multiple myeloma. We identified 641 patients with multiple myeloma who had been treated using novel agents and/or autologous stem cell transplantation with high-dose chemotherapy between January 2006 and June 2014 at nine Japanese hospitals. The patients' characteristics, laboratory data, and clinical courses were retrieved and statistically analyzed. During a median follow-up of 101 weeks, one of eight (12.5 %) HBV carriers developed hepatitis and 9 of 99 (9.1 %) patients with resolved HBV infection experienced HBV reactivation; the cumulative incidences of HBV reactivation at 2 years (104 weeks) and 5 years (260 weeks) were 8 and 14 %, respectively. The nine cases of reactivation after resolved HBV infection had received entecavir as preemptive therapy or were carefully observed by monitoring their HBV DNA levels, and none of these cases developed hepatitis. Among patients with multiple myeloma, HBV reactivation was not rare. Therefore, long-term monitoring of HBV DNA levels is needed to prevent hepatitis that is related to HBV reactivation in these patients.

Help-seeking intentions for early signs of mental illness and their associated factors: comparison across four kinds of health problems.

BACKGROUND: Failure and delay in initial treatment contact for mental disorders has been recognized as an important public health problem. According to the concept of mental health literacy, recognition of symptoms is crucial to making decisions to seek or not seek professional help. The aims of this study were to investigate the types of health problems for which Japanese adults intend to seek help, their preferred sources of help, and the factors associated with help-seeking intentions. METHODS: A cross-sectional web-based survey was conducted in June 2014 among Japanese adults aged 20-59 years. A total of 3308 eligible respondents were included in this study. Help-seeking intentions were measured by listing potential sources of help (including 'would not receive help') and asking which ones would be chosen in four health conditions indicated by irritability, dizziness, insomnia, and depressed mood, respectively. RESULTS: In the case of dizziness, 85.9% of the participants reported a positive help-seeking intention and 42.7% gave first priority to seeking help from formal sources. These percentages were smaller in the cases of insomnia (75.4 and 25.0%), depressed mood (74.9 and 18.7%), and irritability (72.9 and 0.9%). Multiple logistic regression analysis revealed that the factors significantly associated with help-seeking intentions were almost identical across the four health problems. In particular, perception of family and friends regarding help-seeking, psychiatric history, contact with people with mental illness, better health literacy, and neighborhood communicativeness were significantly associated with the overall help-seeking intention and also the help-seeking intention from formal sources for all the problems of dizziness, insomnia, and depressed mood. CONCLUSIONS: The majority of participants indicated their intentions to seek help, but psychological problems (insomnia and depressed mood) were less likely to induce help-seeking intentions than a physical problem (dizziness). Besides developing health literacy skills, community-based interventions for creating a friendly approachable atmosphere and facilitating daily interactions with family, friends, and neighbors may be worth considering as a possible public health strategy for encouraging help-seeking whether for psychological or physical problems.

Impact of Elevated Hemoglobin and Serum Protein on Vasovagal Reaction from Blood Donation.

We conducted a cross-sectional study to elucidate factors contributing to vasovagal reaction (VVR), the most frequent side effect following whole blood and apheresis donations. Complications recorded at the collection sites after voluntary donations by the Japanese Red Cross Tokyo Blood Center (JRC), in the 2006 and 2007 fiscal years, were analyzed by both univariate analysis and the multivariate conditional logistic regression model. Of 1,119,716 blood donations over the full two years, complications were recorded for 13,320 donations (1.18%), among which 67% were VVR. There were 4,303 VVR cases which had sufficient information and could be used for this study. For each VVR case, two sex- and age-matched controls (n = 8,606) were randomly selected from the donors without complications. Age, sex, body mass index (BMI), predonation blood pressure, pulse and blood test results, including total protein, albumin, and hemoglobin, were compared between the VVR group and the control group. In univariate analysis, the VVR group was significantly younger, with a lower BMI, higher blood pressure and higher blood protein and hemoglobin levels than the control group (p<0.001). Furthermore, blood protein and hemoglobin levels showed dose-dependent relationships with VVR incidences by the Cochran-Armitage trend test (p<0.01). For both sexes, after adjusting for confounders with the multivariate conditional logistic regression model, the higher than median groups for total protein (male: OR 1.97; 95%CI 1.76,-2.21; female: OR 2.29; 95%CI 2.05-2.56), albumin (male: 1.75; 1.55-1.96; female: 1.76; 1.57-1.97) and hemoglobin (male: 1.98; 1.76-2.22; female: 1.62; 1.45-1.81) had statistically significant higher risk of VVR compared to the lower than median groups. These elevated serum protein and hemoglobin levels might offer new indicators to help understand VVR occurrence.

Relationship between individual characteristics, neighbourhood contexts and help-seeking intentions for mental illness.

OBJECTIVE: Encouraging help-seeking for mental illness is essential for prevention of suicide. This study examined the relationship between individual characteristics, neighbourhood contexts and help-seeking intentions for mental illness for the purpose of elucidating the role of neighbourhood in the help-seeking process. DESIGN, SETTING AND PARTICIPANTS: A cross-sectional web-based survey was conducted among Japanese adults aged 20-59 years in June 2014. Eligible respondents who did not have a serious health condition were included in this study (n=3308). MAIN OUTCOME MEASURES: Participants were asked how likely they would be to seek help from someone close to them (informal help) and medical professionals (formal help), respectively, if they were suffering from serious mental illness. Path analysis with structural equation modelling was performed to represent plausible connections between individual characteristics, neighbourhood contexts, and informal and formal help-seeking intentions. RESULTS: The acceptable fitting model indicated that those who had a tendency to consult about everyday affairs were significantly more likely to express an informal help-seeking intention that was directly associated with a formal help-seeking intention. Those living in a communicative neighbourhood, where neighbours say hello whenever they pass each other, were significantly more likely to express informal and formal help-seeking intentions. Those living in a supportive neighbourhood, where neighbours work together to solve neighbourhood problems, were significantly more likely to express an informal help-seeking intention. Adequate health literacy was directly associated with informal and formal help-seeking intentions, along with having an indirect effect on the formal help-seeking intention through developed positive perception of professional help. CONCLUSIONS: The results of this study bear out the hypothesis that neighbourhood context contributes to help-seeking intentions for mental illness. Living in a neighbourhood with a communicative atmosphere and having adequate health literacy were acknowledged as possible facilitating factors for informal and formal help-seeking for mental illness.