Universal nucleic acid donor screening revealed epidemiological features of hepatitis E and prevented transfusion-transmitted infection in Japan.

BACKGROUND: More than 45 cases of transfusion-transmitted hepatitis E virus infection (TT-HEV) have been reported in Japan. Therefore, in 2020, universal individual donation nucleic acid amplification testing (ID-NAT) was implemented for HEV. STUDY DESIGN AND METHODS: We characterized HEV NAT-positive blood donors. The number of new HEV infections and the asymptomatic infection rate were estimated using the HEV NAT-positive rate. HEV RNA quantitation, phylogenetic analysis, and antibody tests were performed, and the residual risk of TT-HEV was assessed based on the lookback study results. RESULTS: A total of 5,075,100 blood donations were screened with ID-NAT during the first year of implementation, among which 2804 (0.055%; males: 0.060%, females: 0.043%) were NAT-positive with regional differences. Approximately 270,000 new HEV infection cases were estimated to occur annually in Japan, with an asymptomatic infection rate of 99.9%. The median HEV RNA concentration, excluding cases below the limit of quantification, was 205 IU/mL. Among the 1113 cases where the genotype could be determined, HEV-3 and HEV-4 accounted for 98.8% (1100) and 1.2% (13), respectively. The maximum duration of HEV viremia, including the pre- and post-ID-NAT window periods, was estimated to be 88.2 days. Within the 3 years since ID-NAT implementation, no confirmed cases of breakthrough TT-HEV were observed. DISCUSSION: Multiple indigenous HEV strains are prevalent in Japan, infecting a significant number of individuals. However, since the implementation of ID-NAT, TT-HEV has been prevented due to the test's high sensitivity.

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.

Insights into the diversity of blood donation practice across Asia: How blood collection agencies adapt donor criteria and processes to their population.

BACKGROUND AND OBJECTIVES: Securing an adequate blood supply relies on accurate knowledge of blood donors and donation practices. As published evidence on Asian populations is sparse, this study aims to gather up-to-date information on blood donors and donation practices in Asia to assist planning and strategy development. MATERIALS AND METHODS: Ten blood collection agencies (BCAs) provided 12 months' data on donors who met eligibility criteria or were deferred, as well as details of their donation practices. Body mass index and blood volumes were calculated and analysed. RESULTS: Data on 9,599,613 donations and 154,834 deferrals from six national and four regional BCAs revealed varied donation eligibility and collection practices. Seven used haemoglobin (Hb) criteria below the World Health Organization anaemia threshold. Seven accepted donors weighing <50 kg. Data collection on the weight and height of donors and on deferrals was inconsistent, often not routine. Deferred donors appear to weigh less, with corresponding lower estimated blood volume. CONCLUSION: The diversity in eligibility criteria and donation practices reflects each BCA's strategy for balancing donor health with securing an adequate blood supply. Use of lower Hb criteria substantiate their appropriateness in Asia and indicate the need to define Hb reference intervals relevant to each population. We encourage routine gathering of donor weight and height data to enable blood volume estimation and local optimization of donation volumes. Blood volume estimation formulae specific for the Asian phenotype is needed. Information from this study would be useful for tailoring donation criteria of Asian donors around the world.

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.

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.

Combined impact of HLA-allele matching and the CD34-positive cell dose on optimal unit selection for single-unit cord blood transplantation in adults.

The combined effects of HLA-allele matching at six-loci (HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1) and CD34+ cell dose on clinical outcomes were analyzed in 1,226 adult cases with single-unit unrelated cord blood transplantation. In the six-loci analysis, low HLA-allele matches did not significantly increase the overall mortality compared to higher matches, whereas in the five-loci analysis excluding HLA-DPB1, they caused a higher overall mortality (HR 1.42, p = .002), possibly due to the graft-versus-leukemia effect of HLA-DPB1 mismatches. A lower CD34+ cell dose (<.50 × 105/kg) resulted in higher mortality and lower engraftment; these inferior outcomes were offset by high HLA-allele matches (7-10/10 match), while the inferior outcomes of low HLA-allele matches were improved by increasing the CD34+ cell dose. Consideration of the combined effects of the CD34+ cell dose and HLA matching may expand the options for transplantable units when HLA matching or the CD34+ cell dose is inadequate.

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.

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.

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.

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 health literacy, health information access, health behavior, and health status in Japanese people.

OBJECTIVE: To examine the relationship between health literacy (HL), health information access, health behavior, and health status in Japanese people. METHODS: A questionnaire survey was conducted at six healthcare facilities in Japan. Eligible respondents aged 20-64 years (n=1218) were included. Path analysis with structural equation modeling was performed to test the hypothesis model linking HL to health information access, health behavior, and health status. RESULTS: The acceptable fitting model indicated that the pathways linking HL to health status consisted of two indirect paths; one intermediated by health information access and another intermediated by health behavior. Those with higher HL as measured by the 14-item Health Literacy Scale (HLS-14) were significantly more likely to get sufficient health information from multiple sources, less likely to have risky habits of smoking, regular drinking, and lack of exercise, and in turn, more likely to report good self-rated health. CONCLUSION: HL was significantly associated with health information access and health behavior in Japanese people. HL may play a key role in health promotion, even in highly educated countries like Japan. PRACTICE IMPLICATIONS: In order to enhance the effects of health promotion interventions, health professionals should aim at raising HL levels of their target population groups.

Reading comprehension of health checkup reports and health literacy in Japanese people.

OBJECTIVES: To determine the reading comprehension of health checkup reports in the context of health literacy (HL) in Japanese people. METHODS: A web-based survey was conducted among 424 Japanese adults aged 35-59 years. Participants were asked to read specifically designed health checkup reports and then answer a series of questions to examine whether they accomplished the fundamental purposes of health checkup reports (recognition of the problems, recognition of the risk of illness, recognition of the need for preventive action, and motivation for preventive action). HL was simultaneously measured using the 14-item health literacy scale (HLS-14), the 11-item Lipkus scale (Lipkus-J), and the Newest Vital Sign (NVS-J). RESULTS: About 70 % of the study subjects misread the normal/abnormal classification for at least one items. Those with lower HLS-14 scores were significantly less likely to recognize the problems, the risk of illness, and the need for preventive action for the examinee, and also less likely to express their willingness to take preventive action in compliance with the doctor's advice after having received the health checkup report. Compared with the HLS-14 scores, the Lipkus-J and NVS-J scores showed hardly any association with the reading comprehension of health checkup reports. CONCLUSION: All examinees do not always have an adequate level of HL. HL may be the major determinant of reading comprehension of health checkup reports. For more effective health checkups, health promotion service providers should become aware of the existence of examinees with inadequate HL and address the problem of misreading health checkup results.

Validity and reliability of the Japanese version of the Newest Vital Sign: a preliminary study.

Health literacy (HL) refers to the ability to obtain, process, and understand basic health information and services, and is thus needed to make appropriate health decisions. The Newest Vital Sign (NVS) is comprised of 6 questions about an ice cream nutrition label and assesses HL numeracy skills. We developed a Japanese version of the NVS (NVS-J) and evaluated the validity and reliability of the NVS-J in patients with chronic pain. The translation of the original NVS into Japanese was achieved as per the published guidelines. An observational study was subsequently performed to evaluate the validity and reliability of the NVS-J in 43 Japanese patients suffering from chronic pain. Factor analysis with promax rotation, using the Kaiser criterion (eigenvalues ≥1.0), and a scree plot revealed that the main component of the NVS-J consists of three determinative factors, and each factor consists of two NVS-J items. The criterion-related validity of the total NVS-J score was significantly correlated with the total score of Ishikawa et al.'s self-rated HL Questionnaire, the clinical global assessment of comprehensive HL level, cognitive function, and the Brinkman index. In addition, Cronbach's coefficient for the total score of the NVS-J was adequate (alpha = 0.72). This study demonstrated that the NVS-J has good validity and reliability. Further, the NVS-J consists of three determinative factors: "basic numeracy ability," "complex numeracy ability," and "serious-minded ability." These three HL abilities comprise a 3-step hierarchical structure. Adequate HL should be promoted in chronic pain patients to enable coping, improve functioning, and increase activities of daily living (ADLs) and quality of life (QOL).

The 14-item health literacy scale for Japanese adults (HLS-14).

OBJECTIVES: Most existing tools for measuring health literacy (HL) focus on reading comprehension and numeracy in English speakers. The aim of this study was to develop a generic HL measure for Japanese adults. METHODS: A questionnaire survey was conducted among participants in multiphasic health examinations at a Japanese healthcare facility. HL was measured using the 14-item health literacy scale (HLS-14) that was adapted from the HL scale specific to diabetic patients developed by Ishikawa and colleagues. The 14 items consist of five items for functional HL, five items for communicative HL, and four items for critical HL. The reliability and validity of the HLS-14 were assessed among 1,507 eligible respondents aged 30-69 years. RESULTS: Explanatory factor analysis produced a three-factor solution that was very similar to the original HL scale. Cronbach's alpha indicated satisfactory internal consistency of the functional, communicative, and critical HL scores (0.83, 0.85, and 0.76, respectively). There were no floor or ceiling effects in each HL score. Confirmatory factor analysis revealed an acceptable fit of the three-factor model (comparative fit index = 0.912, normed fit index = 0.905, root mean square error of approximation = 0.082). When the two groups with a total HL score above and below the median (50), respectively, were compared, those who could obtain medication information satisfactorily and those who wanted to participate in making medication decisions were more frequently observed in the group with the higher score. CONCLUSIONS: The HLS-14 demonstrated adequate reliability and validity as a generic HL measure for Japanese adults. This scale can be utilized for measuring functional, communicative, and critical HL in the clinical and public health contexts.

Risk factor analysis of vasovagal reaction from blood donation.

BACKGROUND: Vasovagal reaction (VVR) is the most frequent side effect at blood collection sites. AIMS: To protect donors, factors contributing to VVR were analysed. MATERIALS AND METHODS: Complications following whole blood and apheresis donations have been recorded and accumulated by the Japanese Red Cross Tokyo Blood Centre. A dataset of 43,948 donors who had no complications was prepared as a control by randomly selecting days in each season in the 2006 and 2007 fiscal years. Factors contributing to 4924 VVR incidents in the 2006 and 2007 fiscal years were analysed by univariate and multivariate logistic regression. RESULTS: The age, weight, body mass index (BMI), predonation systolic and diastolic pressure, and circulating blood volume were lower, and the pulse was higher, for the VVR group compared to the control group (p<0.0001). The VVR group had more female donors, less sleep, and more time since a meal than the control. In multivariate analysis, significant risk factors for 400 ml whole blood donors, which are the majority of donors, were an age <50 years, being female, a BMI <25, pulse ≥90/min, sleep duration <8 h, the time after eating ≥4 h, a first time donation and circulating blood volume of <4.3 l. Sleep duration of <6 h was shown to be a VVR risk as much as a first time donation. CONCLUSION: From our analysis, the amount of sleep obtained the previous night should be considered at the reception of donors.

[Epidemiological study of fractures in Japanese children and adolescents].

We reviewed our previous population-based survey regarding fractures in 55,464 Japanese children, conducted in 2001. (total : 773 fractured cases [prevalence 1.4%] , males : 527 casesc [1.9%] females : 246 cased [0.9%] , respectively) . The peak age-sex-specific incidences occurred at 7(th) - 8(th) grade (ages 12 to 13 years) for males, and at 5(th) - 6(th) grade (ages 10 to 11 years) for females, which was matched by the age of growth spurt. The incidences had a monthly variation, with peaks in spring and autumn (May, June, September, October, and November) . Furthermore, significant differences in fractures' characteristics were found between children in primary school and those in middle school. This data may contribute preventing fractures in Japanese children.