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Background We aimed to develop a chemoimmunotherapy regimen consisting of a novel Wilms’ tumor 1 (WT1) peptide-pulsed dendritic cell (WT1-DC) vaccine and multiagent chemotherapy and to investigate the safety, clinical outcomes, and WT1-specific immune responses of patients with unresectable advanced pancreatic ductal adenocarcinoma (UR-PDAC) who received this treatment.Methods Patients with UR-PDAC with stage III disease (locally advanced (LA-PDAC; n=6)), stage IV disease (metastatic (M-PDAC; n=3)), or recurrent disease after surgery (n=1) were enrolled in this phase I study. The patients received one cycle of nab-paclitaxel plus gemcitabine alone followed by 15 doses of the WT1-DC vaccine independent of chemotherapy. The novel WT1 peptide cocktail was composed of a multifunctional helper peptide specific for major histocompatibility complex class II, human leukocyte antigen (HLA)-A*02:01, or HLA-A*02:06 and a killer peptide specific for HLA-A*24:02.Results The chemoimmunotherapy regimen was well tolerated. In the nine patients for whom a prognostic analysis was feasible, the clinical outcomes of long-term WT1 peptide-specific delayed-type hypersensitivity (WT1-DTH)-positive patients (n=4) were significantly superior to those of short-term WT1-DTH-positive patients (n=5). During chemoimmunotherapy, eight patients were deemed eligible for conversion surgery and underwent R0 resection (four patients with LA-PDAC, one patient with M-PDAC, and one recurrence) or R1 resection (one patient with M-PDAC), and one patient with LA-PDAC was determined to be unresectable. Long-term WT1-DTH positivity was observed in three of the four patients with R0-resected LA-PDAC. These three patients exhibited notable infiltration of T cells and programmed cell death protein-1+ cells within the pancreatic tumor microenvironment (TME). All patients with long-term WT1-DTH positivity were alive for at least 4.5 years after starting therapy. In patients with long-term WT1-DTH positivity, the percentage of WT1-specific circulating CD4+ or CD8+ T cells that produced IFN-γ or TNF-α was significantly greater than that in patients with short-term WT1-DTH positivity after two vaccinations. Moreover, after 12 vaccinations, the percentages of both circulating regulatory T cells and myeloid-derived suppressor cells were significantly lower in patients with long-term WT1-DTH-positive PDAC than in short-term WT1-DTH-positive patients.Conclusions Potent activation of WT1-specific immune responses through a combination chemoimmunotherapy regimen including the WT1-DC vaccine in patients with UR-PDAC may modulate the TME and enable conversion surgery, resulting in clinical benefits (Online supplemental file 1).Trial registration number jRCTc030190195.

Abstract Background Public health professionals have prepared and distributed many messages and materials to convince the public to adopt healthy behaviors or reduce risky behaviors. However, health promotion materials do not always have the desired effect due to a lack of ability to engage target audience. This study examined the effectiveness of humor appeal (i.e. using humor as an advertising technique to attract attention and increase acceptance of the message) in health promotion materials and how to use it effectively. Methods Total 17 printable posters with different frames (loss- vs. gain-framed) × tones (humorous vs. non-humorous) × topics (advance care planning, cancer screening, donor registry, smoking cessation, and physical activity) were created and evaluated for comprehensibility, persuasiveness, and resistance through two web-based surveys. Participants who were Japanese adults aged 25–64 years were randomly assigned one of the posters (200 people each) and asked to rate it. The overall score was calculated as the persuasiveness score (EHPM 2017;22:69) minus the resistance score (EHPM 2022;27:20). Results In the advance care planning case, the highest overall score was found in the gain-framed humorous poster, followed by the loss-framed humorous poster, and the non-humorous poster (p = 0.007). In the other 4 cases, the posters using humorous illustrations received a significantly lower scores than the non-humorous poster(s). Conclusion The use of humor appeal can help improve the acceptability and persuasiveness of the message when dealing with a little-known resistance-prone health topic. Humor appeal will provide an effective hook to direct public attention to what they do not know or care about in public health communication.

Abstract Background Texture and color enhancement imaging (TXI) enhances the changes in endoscopic features caused by gastric neoplasms, such as redness/whiteness and elevation/depression. This study aimed to demonstrate the effectiveness of TXI in improving the visibility of gastric neoplasms compared with white light imaging (WLI) using conventional (CE) and newly developed endoscopes (NE). Methods We recruited patients who were histologically diagnosed with gastric neoplasms; endoscopy was performed, and gastric neoplasms photographed using three imaging modalities, including WLI, TXI mode 1 (TXI-1) and TXI mode 2 (TXI-2). Two different endoscopes (CE and NE) were used for the same patients. Six endoscopists provided the visibility scale scores ranging from 1 (poor) to 4 (excellent) for gastric neoplasms. The primary outcome was the visibility scale scores based on each modality and endoscope. The secondary outcome was the identification of factors including H. pylori infection, atrophy, location, size, morphology, histological diagnosis and intestinal metaplasia that affect the differences in visibility scale scores between TXI-1/TXI-2 and WLI. Results Fifty-two gastric neoplasms were analyzed. The mean visibility scale scores with the NE were 2.79 ± 1.07, 3.23 ± 0.96 and 3.14 ± 0.92 for WLI, TXI-1 and TXI-2, respectively. The mean visibility scales with the CE were 2.53 ± 1.10, 3.04 ± 1.05 and 2.96 ± 1.92 for WLI, TXI-1 and TXI-2, respectively. For both endoscopes, significant differences were observed in visibility scale scores between WLI and TXI-1 (p

Background: This study examined the association between neurological symptoms and quality of life (QoL) in patients with neurofibromatosis type 2 (NF2) using a national database of all patients who newly claimed for medical expense subsidies in Japan from 2015 to 2019. Methods: The Japanese Ministry of Health, Labour and Welfare provided access to the “National Database of Designated Intractable Diseases of Japan” containing the “Medical Certificates of Designated Intractable Diseases” of all patients with NF2. The database included information on five items of QoL: “mobility,” “self-care,” “usual activities,” “pain/discomfort,” and “anxiety/depression.” To examine the association between the presence/absence of neurological symptoms and QoL, multivariable logistic regression analyses were performed, adjusted for potential confounders. Results: Data from 187 patients (97 females and 90 males; mean (standard deviation) age, 43.1 (17.9) years) were analyzed. Overall, 31% to 55% of patients were recorded as having moderate/severe impairment of QoL. Spinal dysfunction was significantly associated with deterioration of all components of QoL, whereas speech dysfunction and hemiparesis were specifically associated with physical health-related components of QoL. Spinal dysfunction, facial nerve palsy, and age 25–64 years were significantly associated with “anxiety/depression.” Conclusions: In the present epidemiological study using a national database of NF2 in Japan, spinal dysfunction was significantly associated with deterioration of all components of QoL, including subjective and mental health-related components of QoL, whereas speech dysfunction and hemiparesis were specifically associated with physical health-related components of QoL.

Background: This study examined the association between dermatological, neurological, and bone manifestations of neurofibromatosis type 1 (NF1) and quality of life (QoL) in patients with NF1 using a nationwide database of all patients who newly claimed for medical expense subsidies in Japan from 2015 to 2019. Methods: The Japanese Ministry of Health, Labour and Welfare provided the “National Database of Designated Intractable Diseases of Japan” containing clinical and personal records (“Medical Certificates of Designated Intractable Diseases”) of all patients with NF1 following approval of the study protocol. To examine the association between the severity of symptoms and QoL, multinominal logistic regression analyses were performed, adjusted for potential confounders. Results: The final study population consisted of 1,487 patients (775 females and 712 males; mean (standard deviation) age, 45.4 (17.9) years). More than 50% and nearly 45% of participants were recorded as having moderate or severe “pain/discomfort” and “anxiety/depression,” respectively. The severity of neurological symptoms was significantly associated with all components of QoL, whereas the severity of dermatological symptoms was significantly associated with only moderate or severe subjective and mental health-related components of QoL, and the severity of bone lesions was associated with only moderate or severe physical health-related components of QoL. Subjective and mental health-related components of QoL tended to be deteriorated more than physical health-related components of QoL in younger and female patients. Conclusions: Severities of neurological and dermatological symptoms were significantly associated with subjective and mental health-related components of QoL, while the severity of bone symptoms was associated with only moderate and severe deterioration of physical health-related components of QoL.

Background: This study aimed to examine population-based characteristics of non-fatal self-harm in an urban area during pre- and peri-pandemic periods of COVID-19 by sex, age, and severity of self-harm, using pre-hospital medical emergency records. Methods: We used a registry of all pre-hospital medical records of self-harm cases that occurred in Kawasaki City, Japan, between January 2018 and December 2021. Adjusted incidence rate ratios (IRRs) with 95% confidence intervals (CIs) were calculated using Poisson regression models with the log-transformed population by year, sex, age group, and ward as an offset term. Results: During the 4-year study period, 1,534 patients were transported by ambulance due to non-fatal self-harm and were alive on arrival at the hospital. Among women, the number of non-fatal self-harm cases increased by 1.2-fold in 2021 compared with that in 2018. The incidence rate of “severe” non-fatal self-harm among men aged 19 years or younger in 2021 (IRR 4.82, 95% CI 1.25–18.65) and that among women aged 50–59 years in 2020 (IRR 2.51, 95% CI 1.06–5.95) significantly increased compared with that 2018 and 2019. The incidence rate of “mild” self-harm among women aged 20–29 years tended to be higher in 2021 than in 2018 and 2019 (IRR 1.42, 95% CI 0.95–2.12, P = 0.085). Conclusions: During the peri-pandemic period of COVID-19, the incidence rate of “severe” non-fatal self-harm among men aged 19 years or younger and women aged 50–59 years, as well as that of “mild” self-harm among women aged 20–29 years, sharply increased compared with that during the pre-pandemic period. Our findings suggest that in urban areas during public health crises such as a pandemic, it is important to take measures to reduce the risk of non-fatal self-harm in young women, in addition to strengthening counseling and support for young women at risk for completed suicide.

Abstract Aims/Introduction We aimed to study the relationships among the copper (Cu)/zinc (Zn) ratio, inflammatory biomarkers, and the prevalence of diabetic kidney disease (DKD) in patients with type 2 diabetes. Materials and Methods A cross‐sectional study was performed on 651 patients with type 2 diabetes. DKD was defined as a urinary albumin‐to‐creatinine ratio of ≥30 mg/g creatinine and/or an estimated glomerular filtration rate using cystatin C of

Abstract Background Taking advantage of the current advances in diagnostic imaging modalities, including endoscopic ultrasonography (EUS), and due to the increased attention to ectopic fat accumulation in the pancreas following the rising trend of metabolic syndrome, we qualitatively assessed the clinical implication of pancreatic steatosis by EUS in this study. Methods The study included 243 patients that were divided into four groups. The correlation between the average echogenicity of the pancreas and that of the control organs and the key clinical data of all study patients were collectively analyzed. The cut‐off point of the pancreas‐control (PC) ratio in EUS and liver‐control (LC) ratio on abdominal ultrasound were determined from the population distribution and the obtained median values. Results With the cut‐off point of 1.30 for the PC ratio and 1.20 for the LC ratio, sex, the Brinkman index, habitual alcohol drinkers, and fatty pancreas were significant factors. The associations between each relevant factor in fatty pancreas, metabolic syndrome in the fatty liver group, and age in the pancreatic cancer group were all significant in the analysis. In addition, we investigated whether the PC ratio differed according to age and staging in pancreatic cancer patients. Interestingly, the PC ratio was lower in the advanced stage group than in the early‐stage group. Conclusion Our results suggest that, irrespective of the degree, ectopic fat infiltration in the pancreas could be a specific clinical phenotype of serious pancreatic diseases, including pancreatic cancer, especially in high‐risk patients.

Abstract Background Both activated tumor-infiltrating lymphocytes (TILs) and immune-suppressive cells, such as regulatory T cells (Tregs), in the tumor microenvironment (TME) play an important role in the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC). Methods The densities of TILs, programmed death receptor 1 (PD-1) + T cells, and forkhead box P3 (Foxp3) + T cells were analyzed by immunohistochemical staining. The associations of the immunological status of the PDAC microenvironment with overall survival (OS) time and disease-free survival (DFS) time were evaluated. Results PDAC patients with a high density of TILs in the TME or PD-1-positive T cells in tertiary lymphoid aggregates (TLAs) demonstrated a significantly better prognosis than those with a low density of TILs or PD-1-negativity, respectively. Moreover, PDAC patients with high levels of Foxp3-expressing T cells showed a worse prognosis than those with low levels of Foxp3-expressing T cells. Importantly, even with a high density of the TILs in TME or PD-1-positive T cells in TLAs, PDAC patients with high levels of Foxp3-expressing T cells showed a worse prognosis than patients with low levels of Foxp3-expressing T cells. A PDAC TME with a high density of TILs/high PD-1 positivity/low Foxp3 expression was an independent predictive marker associated with superior prognosis. Conclusion Combined assessment of TILs, PD-1+ cells, and Foxp3+ T cells in the TME may predict the prognosis of PDAC patients following surgical resection.

Background: Students and workers have been subjected to increased levels of psychological distress due to the quarantine policy and containment measures during the COVID-19 pandemic. This scoping review aimed to present an overview of published evidence regarding formal and informal help-seeking intentions/behaviors for non-mental health-related issues as well as mental health-related issues among students and workers during the pandemic. Methods: In June 2022, we searched MEDLINE, APA PsycNet, and CINAHL for articles reporting the state of help-seeking intentions/behaviors among students and workers during the pandemic. Peer-reviewed original articles published in English were selected. Results: In total, 150 articles were identified, and 12 articles were selected for final analysis after removing articles that met the exclusion criteria. Three studies targeted university students, and nine targeted healthcare workers. Study settings were restricted to Western countries and China. Of the 12 studies, 11 were observational and predominantly cross-sectional studies. Two longitudinal studies using student samples suggested that university students became more reluctant to seek help from both formal and informal sources during the COVID-19 pandemic compared to before, despite the increased need for support during the pandemic. Among healthcare workers, the proportions of those who sought help from formal sources in person were low (7–26%), even among those with mental health issues, despite the increase in the need for mental health services. One randomized controlled study reported that a brief video-based intervention increased treatment-seeking intentions among healthcare workers in the intervention group compared with the non-intervention group. Conclusions: The present review revealed that, although most studies included in the final analysis were cross-sectional, intentions/behaviors to seek help from both formal and informal sources decreased among university students, even those with mental health issues. Among healthcare workers, while the frequency of help-seeking from formal sources in person was low, a brief online intervention was suggested to be useful for promoting help-seeking from formal sources. During public health crises such as the COVID-19 pandemic, system and infrastructure development of online help-seeking services could potentially promote formal and informal help-seeking intentions/behaviors for diverse issues, including non-mental health-related issues, among university students and healthcare workers/providers.

Background: For patients with neurofibromatosis type 2 (NF2), maintaining an independent state of living is important. The present study aimed to examine the loss of social independence (i.e., a status that patients can work and go to school) and its contributing factors in patients with NF2 using data from a national registry in Japan. Methods: This longitudinal study used a registry database containing information on patients with NF2 who had submitted initial claims to receive medical expense subsidies between 2004 and 2010. Patients with “employed,” “studying,” and “housekeeping” categories were classified as “socially independent.” Patients who were socially independent at baseline were followed-up for up to nine years. The primary outcome of the present study was the loss of social independence during the follow-up period, which was defined as the change in status from being socially independent to socially dependent. First, we examined longitudinal associations between demographic variables and neurological symptoms at baseline and the loss of social independence. Second, we examined whether the occurrence of neurological symptoms is associated with a loss of social independence in patients. Results: A total of 156 patients were included in the present study. During the follow-up period, 37 (23.7%) patients experienced a loss of social independence. In the first analysis, the multivariate logistic regression model showed that the loss of social independence was significantly more frequent among patients with spinal dysfunction than among patients without. In the second analysis, logistic regression analyses showed that neurological symptoms, including bilateral hearing loss, facial nerve palsy, cerebellar dysfunction, decreased facial sensation, speech dysfunction (dysphagia/dysarthria and aphasia), double vision, blindness, hemiparesis, and seizures, were significantly associated with loss of social independence. Conclusions: The occurrence of various neurological symptoms of NF2 can hinder social independence in the long term. Medical service providers need to observe patients while considering the risks, and provide appropriate support to address neurological symptoms that can restrict social independence, as this will lead to maintaining social engagement.

Abstract Aims/Introduction To identify thresholds for postprandial hyperglycemia and hypertriglyceridemia predictive of all‐cause mortality in patients with type 2 diabetes. Materials and Methods A total of 1,928 patients with type 2 diabetes visited our clinic for the first time from 1995 to 1999 and were followed up for ≥1 year. During the first year, 2‐h post‐breakfast blood glucose (2h‐BG) levels were measured in 1,122 patients (BG cohort) and postprandial serum triglyceride (ppTG) levels were measured in 1,826 patients (TG cohort). Patients were retrospectively followed until 2017 and administered questionnaires. Associations between 2h‐BG and ppTG levels and mortality risk were assessed by the multivariate Cox regression analysis. Results Over of 17,429 person‐years, 162 deaths occurred in the BG cohort, and over 28,026 person‐years, 253 deaths occurred in the TG cohort. Hazard ratios (HRs) with 95% confidence intervals for all‐cause mortality per 1‐standard deviation increases in 2h‐BG and ppTG were 1.34 (1.08–1.67) and 1.24 (1.06–1.45), respectively. HRs showed increasing trends across quintiles of 2h‐BG (P = 0.034) and ppTG (P = 0.007). The HR was significantly elevated (2.37, 1.26–4.47) in the fifth quintile of 2h‐BG (≥13.8 mmol/L) compared with the first quintile (

Abstract Background This study aimed to examine the change in health status of the general public after starting the COVID-19 pandemic and its association with changes in workload and lifestyle. Methods A web-based survey was conducted in November 2020, about 9 months after starting the COVID-19 pandemic in Japan, among 8000 Japanese men and women aged 25–64 years. Participants asked for the changes after starting the COVID-19 pandemic in health status, workload, daily life, and health behavior. Ordinal logistic regression was performed to elucidate factors associated with deterioration in general health status. Results A deterioration in general health status was reported by 17.0% of male and 19.4% of female. There has been a clear shift to sedentary life with decreasing moderate activity and increasing screen time. The multivariate analysis revealed that deteriorated work style, increased burden of housework, decreased moderate activity, increased digital media exposure, and increased body weight were significantly associated with deteriorating health status. Conclusion Both men and women have experienced significant changes in workload and lifestyle since the COVID-19 pandemic started. People should be aware of the risks associated with their recent life changes and take self-care measures to prevent serious health consequences.

Abstract Aims/Introduction We assessed the relationship between diabetic retinopathy (DR) and/or diabetic kidney disease (DKD) according to their severity and all‐cause, cancer, vascular and non‐cancer non‐vascular mortality in real‐world patients with type 2 diabetes. Materials and Methods A total of 1,902 patients with type 2 diabetes were enrolled from 1995 to 1999 and followed to 2017. At baseline, DR was diagnosed in 374 patients, DKD in 529, vision‐threatening DR in 123 and advanced DKD in 287. Patients were classified by the status of DR and DKD. Multivariate Cox regression analysis was carried out. Results There were 266 deaths during a median follow‐up period of 18.6 years. Among these, 92 were from cancer, 78 were from vascular causes and 82 were from non‐cancer non‐vascular causes. DR and/or DKD predicted all‐cause, vascular and non‐cancer non‐vascular mortality, but not cancer mortality. Similarly, vision‐threatening DR and/or advanced DKD predicted all‐cause, vascular and non‐cancer non‐vascular mortality, but not cancer mortality. Hazard ratios for all‐cause, vascular and non‐cancer non‐vascular mortality were highest in the DR(+)DKD(+) group, and higher in the DR(−)DKD(+) and the DR(+)DKD(−) groups than in the DR(−)DKD(−) group. The results for vision‐threatening DR and advanced DKD were similar. The interaction for non‐cancer non‐vascular mortality, but not all‐cause and vascular mortality, between DR and DKD and between vision‐threatening DR and advanced DKD might be significant. Conclusions DR and DKD may be jointly and independently associated with all‐cause, vascular and non‐cancer non‐vascular mortality, but not cancer mortality, according to their severity in real‐world patients with type 2 diabetes.

Abstract Aims/Introduction There is little evidence on the role of postprandial glycemia in the incidence of diabetic retinopathy (DR) in a real‐world setting. We aimed to assess the effect of postprandial hyperglycemia at clinic visits on the incidence of DR in patients with type 2 diabetes, and whether its effect differs depending on glycated hemoglobin (HbA1c) values and age. Materials and Methods Intrapersonal mean blood glucose levels at 1–2 h post‐breakfast (1–2h‐PBBG), post‐lunch (1–2 h‐PLBG) and both (1–2h‐PBLBG) during 2 years from the first visit were used as baseline data. This retrospective cohort study enrolled 487, 323 and 406 patients who had 1–2h‐PBLBG, 1–2h‐PBBG and 1–2h‐PLBG measurements, respectively. These three groups were followed from 1999 up through 2017. Results DR occurred in 145, 92 and 126 patients in the 1–2h‐PBLBG, 1–2h‐PBBG and 1–2h‐PLBG groups, respectively. Multivariate Cox regression analysis showed that the mean 1–2h‐PBLBG, 1–2h‐PBBG and 1–2h‐PLBG levels were significant predictors of DR, independent of mean HbA1c. In patients with mean HbA1c

Background: The present study aimed to examine the association between the presence/absence of help-seeking behavior (ie, behavior aimed at obtaining assistance from others to improve a situation or problem) and psychological distress among private and public employees by age group using a nationally representative sample of the Japanese population. Methods: The present study analyzed data obtained from the 2016 Comprehensive Survey of Living Conditions, a nationwide cross-sectional survey. Of 568,426 participants, 78,284 private and public employees aged 20 to 59 years, who were receiving no mental health services at the time of the survey and reported at least one stressor in daily life, were eligible. The primary outcome measure was self-rated psychological distress as measured by the Kessler Psychological Distress Scale. Multiple logistic regression analyses were carried out separately by age group, adjusting for sociodemographic and job/life-related factors. Results: The proportion of participants not showing help-seeking behavior was significantly higher among those aged 40–59 years compared to those aged 20–39 (30.5% and 22.7%, respectively; P < 0.001). Participants without help-seeking behavior had significantly higher odds ratios (ORs) for psychological distress, regardless of age group (OR = 1.9 [95% confidence interval (CI), 1.6–2.0] and OR = 1.6 [95% CI, 1.4–1.7] for the age 20–39 years and 40–59 years groups, respectively), compared to those showing help-seeking behavior. Conclusions: Participants not showing help-seeking behavior were more likely to have severe psychological distress, and this trend appeared to be slightly stronger among those aged 20–39 years. These findings suggest that promoting help-seeking behavior is important for improving mental health among workers.

Abstract Background No study to date has followed disease progression in patients with neurofibromatosis type 1 (NF1), including the incidence of various manifestations, using a national registry. Here we examined the state of NF1 progression using a nationwide registry of patients who submitted claims to receive medical expense subsidies for NF1 in Japan over a five-year period. A total of 342 eligible patients (194 females and 148 males) with NF1 who newly submitted claims for medical expense subsidies in Japan in 2008 were followed until 2012. Results More than half of the patients were classified as Stage 5 in 2008. Of the eligible patients, 205 (60%) submitted claims to renew the subsidies between 2009 and 2012. During the study period, NF1 stage progressed in 30 patients, yielding an overall stage progression rate of 19% and progression incidence rate per 100 person-years of 12.2. Both stage progression rate and progression incidence rate were the highest in the 0–19 year age group at the time of registration and, as compared to other age groups, progression of neurological and bone manifestations was more prevalent in this age group. Conclusions The progression of neurological and bone manifestations was more prevalent in the 0–19 year age group compared to other age groups. The registry we used in the present study is useful for understanding the characteristics of patients with uncommon conditions, such as NF1. Our findings also highlight the feasibility of conducting quality research using registries of patients with rare diseases, such as NF1, that were not designed specifically for scientific research.

Abstract Background The persuasive effect of health messages can depend on message features, audience characteristics, and target behaviors. The objective of this study was to compare the responses to persuasive messages encouraging professional help seeking for depression between individuals with and without psychological distress. Methods A cross-sectional web-based survey was conducted on Japanese adults aged 35–45 years, who randomly received one of three persuasive messages that aimed to promote help-seeking intentions for depression. The primary message statements were as follows: (1) depression can happen to anyone, (2) depression needs treatment, and (3) depression improves with treatment. Participants rated the messages in terms of comprehensibility, persuasiveness, emotional response, and intended future use. Help-seeking intention for depression was measured using vignette methodology before and after exposure to the messages. Eligible participants who had not received medical treatment for their mental disorders were classified as either distressed (K6 score ≥ 5, N = 824) or non-distressed (K6 score

Background: In Japan and elsewhere, there is major concern over individuals who are uninterested in health and reluctant to change their health behaviors. While previous studies have investigated cognitive and behavioral characteristics in this population, there is limited evidence on whether they recognize the significance of health, nor is it clear how to motivate necessary behavior changes. This study identified specific characteristics of positive psychological and behavioral change in individuals who were uninterested in health, then constructed a model for their behavior change process, as advised via professional health expertise in the Japanese context. Methods: This qualitative survey study was conducted among 86 health professionals (public health nurses, registered dieticians, and city/prefectural employees). These participants reported their demographic characteristics (gender, age, job, and length of service) and entered free descriptions concerning perceived cognitive and behavior changes in individuals who were uninterested in health. Finally, we thematically analyzed the contents on psychological/behavioral change and constructed a thematic map. Results: We obtained 409 relative descriptive codes and four main themes, including (1) Health awareness: Recognize the significance of health via personal experience and/or illness among family/friends; (2) Psychological readiness: Preparative psychological state toward health behavior; (3) Gateway behavior: Precursory behavior leading to health behavior; and (4) Health behavior: Traditional healthy lifestyle behavior, with 45 subthemes. We constructed the abovementioned thematic map according to the Transtheoretical Model. Herein, health awareness may catalyze changes in health behavior, while changes in both psychological readiness (e.g., new interest in health behaviors and attitude toward appearance) and gateway behaviors (e.g., new points of discussion and information gathering) may arise before changes in health behavior. Conclusions: This study clarified positive cognitive and behavior changes in individuals who were uninterested in health and elucidated their behavior change process. As behavior changes in such individuals tend to be rigid, they are often left behind by health care systems and programs. In this regard, we identified pertinent cognitive and behavioral characteristics during the behavior change process and constructed a relevant model. These findings should be useful in developing interventions that can motivate the desire for behavior change.

AimTo evaluate the cost-effectiveness of therapeutic strategies initiated at different stages of liver fibrosis using three direct-acting antivirals (DAAs), sofosbuvir-ledipasvir (SL), glecaprevir-pibrentasvir (GP), and elbasvir plus grazoprevir (E/G), for Japanese patients with chronic hepatitis C (CHC) genotype 1.MethodsWe created an analytical decision model reflecting the progression of liver fibrosis stages to evaluate the cost-effectiveness of alternative therapeutic strategies applied at different fibrosis stages. We compared six treatment strategies: treating all patients regardless of fibrosis stage (TA), treating individual patients with one of four treatments starting at four respective stages of liver fibrosis progression (F1S: withholding treatment at stage F0 and starting treatment from stage F1 or higher, and three successive options, F2S, F3S, and F4S), and administering no antiviral treatment (NoRx). We adopted a lifetime horizon and Japanese health insurance payers' perspective.ResultsThe base case analysis showed that the incremental quality-adjusted life years (QALY) gain of TA by SL, GP, and E/G compared with the strategies of starting treatments for patients with the advanced fibrosis stage, F2S, varied from 0.32 to 0.33, and the incremental cost-effectiveness ratios (ICERs) were US$24,320, US$18,160 and US$17,410 per QALY, respectively. On the cost-effectiveness acceptability curve, TA was most likely to be cost-effective, with the three DAAs at the willingness to pay thresholds of US$50,000.ConclusionsOur results suggested that administration of DAA treatment for all Japanese patients with genotype 1 CHC regardless of their liver fibrosis stage would be cost-effective under ordinary conditions.

Background: Pretesting is the key to understanding how the intended audience will react to the message. Resistant reactions affect message processing or can lead to undesirable boomerang effects. The objective of this study was to develop a rating scale for measuring active (reactance) and passive (disengagement) resistance to persuasive health messages. Methods: Six candidate items (3 items for disengagement and 3 items for reactance) were generated based on literature review. A web-based survey was conducted among Japanese adults aged 25–64 years to verify the reliability and validity of the 6-item resistance scale. Participants were asked to rate one of the advance care planning (ACP) promotion messages. All scale items were scored on a 1-to-5 point Likert scale and they were averaged to produce the resistance score. Results: Explanatory factor analysis revealed a two-factor solution that agreed with the disengagement and reactance domains, respectively. Correlation coefficients between each set of items ranged between 0.30–0.69. Cronbach alpha (0.86) indicated satisfactory internal consistency of the set of items. Confirmatory factor analysis showed a good fit of the two-factor model with CFI = 0.998, SRMR = 0.011, and RMSEA = 0.041. The resistance score showed a moderate positive correlation with negative emotional responses (displeasure γ = 0.55, anger γ = 0.53) and was significantly inversely related to the persuasiveness score (γ = −0.50). Multivariable logistic regression analysis showed that the odds ratio for ACP intention per 1-point increase in the resistance score was 0.47 (95% confidence interval 0.40–0.56) with adjustment for the persuasiveness score. Conclusion: The 6-item resistance scale exhibited adequate reliability and validity for measuring audience resistance when applied to the ACP promotion messages in Japanese people. The scale will be useful for pretesting health messages to make them more acceptable to the intended audience. Trial registration: Not applicable; this is not a report of intervention trial.

The estimated 20-year renal survival rate of immunoglobulin A (IgA) nephropathy is approx. 60%, but it is difficult to determine the 'big picture' for IgA nephropathy because a biopsy is essential for its diagnosis. Here we attempted to determine the longer and more precise renal prognosis of IgA nephropathy. We examined 310 patients with primary IgA nephropathy. Using the patients' clinical records and histological reports from our hospital and other clinics, we surveyed their renal prognoses and treatments within 1 year post-biopsy, and we sent questionnaires to the patients who had stopped visiting any hospital. We set renal death as the primary endpoint and analyzed factors related to renal death. The total patient cohort was 267: 159 males, 108 females; average age at biopsy, 37.7 years; average estimated glomerular filtration rate (eGFR), 69.7 mL/min/1.73m2; urinary protein, 1.3 g/day. The mean follow-up duration was prolonged to 13.8±8.9 years (vs. 9.2±8.5 years using only medical records). The 10- and 20-year follow-up rates were 61.7% and 27.3%. The 10-, 20-year renal survival rates were 83.6% and 72.5%. Lower eGFR, hypertension, and smoking were revealed as factors independently related to renal death. To study survival of relatively benign diseases such as IgA nephropathy, longer survival rate was affected by many censoring cases. The results regarding the long-term renal prognoses of IgA nephropathy patients (including those with a mild phenotype) obtained by our analysis of a questionnaire sent to the patients provided more precise and longer-term prognoses compared to earlier studies.

Texture and color enhancement imaging (TXI) has been developed as an image-enhanced endoscopy technology. TXI mode2 enhances texture and brightness, and TXI mode1 also enhances color. This study aims to assess the color differences in squamous cell carcinoma (SCC) suspicious lesions in the pharynx and esophagus using white light imaging (WLI), TXI mode1, TXI mode2, and narrow-band imaging (NBI). A total of 59 SCC suspicious lesions from 30 patients were analyzed. The color differences (ΔE) between the lesion and the surrounding mucosa were calculated for each modality. The color value was assessed using the Commission Internationale d’Eclairage L*a*b* color space. The visibility of the lesion in each modality was evaluated and compared to that in the WLI by six endoscopists. The mean ΔE values in the WLI, TXI mode1, TXI mode2, and NBI were 11.6; 18.6; 14.3; and 17.2, respectively, and the ΔE values of TXI mode1, TXI mode2, and NBI were significantly higher than those of the WLI (p < 0.001). No lesions had worse visibility, and 62.5% (37/59) had improved visibility, as assessed by more than half of the endoscopists in TXI mode1. TXI mode1 can enhance color changes and improve the visibility of SCC suspicious lesions in the pharynx and esophagus, compared to WLI.

Abstract Background Communicating health messages is an important way to influence people’s behaviors towards health issues. Providers need to incorporate audience’s perspective to design more persuasive messages. This study aimed to develop rating scales for measuring audience’s perception of effectiveness of health messages in Japanese people. Methods The comprehensibility scale including five items and the persuasiveness scale including seven items were designed based on literature review. A cross-sectional web-based survey was conducted among Japanese adults aged 35–45 years to assess the reliability and validity of the scales. Participants were asked to rate a text message that encouraged help-seeking intention for insomnia. All scale items were scored on a 1-to-5 point Likert scale, and they were averaged to produce an overall score for each scale. Results Explanatory factor analysis revealed a two-factor solution that agreed with the comprehensibility and persuasiveness scales, respectively. Correlation coefficients between each set of items ranged between 0.63–0.87 for the comprehensibility scale and 0.37–0.76 for the persuasiveness scale. Cronbach alpha (0.88) indicated satisfactory internal consistency of the set of items. The mean (SD) of the comprehensibility and persuasiveness scores were 3.70 (0.82) and 3.15 (0.61), respectively, without ceiling or floor effects. These scores were significantly associated with intended future use of the message. The proportion of participants who reported a positive help-seeking intention for insomnia was significantly higher in the higher score groups for both scales. Multiple logistic regression analysis showed that the comprehensibility and persuasiveness scores were significantly associated with the help-seeking intention for insomnia. Conclusion The proposed rating scales exhibited adequate reliability and validity for measuring the comprehensibility and persuasiveness of insomnia health-seeking message in middle-aged Japanese people. Further studies are needed to confirm the generalizability of the results, but these scales may be useful for pretesting a health message with audience members to make it more acceptable and persuasive to the intended audience. Trial registration Not applicable; this is not a report of intervention trial.

Long working hours and a lack of sleep have been suggested to negatively affect the safety of workers. Here, we examined the association between long working hours/sleep-related problems and near-misses/injuries in industrial settings using a nationally representative sample of workers in Japan. Based on the composition ratio of workers by industry, sex, and age in Japan, data from a web-based cross-sectional survey for 18,682 participant full-time workers (7,098 female and 11,584 male; mean age, 43.7 [standard deviation 11.1] years) were analyzed. Nearly 30% and 5% of participants reported any types of near-misses during the past six months and injuries during the past year, respectively. For all types of near-misses and some types of injuries, a significant difference in frequency distribution was observed by industry. After adjustment for demographic, job-, and life-related variables, participants who worked long hours (i.e., more than 51 hours per week) were more likely to report job-related near-misses/injuries than those who worked 35-40 hours per week. The presence of sleep-related problems was also significantly related to near-misses and injuries. However, while sleep-related problems were significantly associated with near-misses/injuries in all industries, the association between long working hours and near-misses/injuries differed by industry. Odds ratios for near-misses/injuries were strongly significant in the "transport/postal services" industry for those who worked more than 51 hours per week compared to those who worked 35-40 hours per week. Comprehensive protective measures for workers, including (1) reducing total hours of service/job-related fatigue, (2) maintaining sufficient sleep hours/good sleep, and (3) increasing awareness about the impact of overwork/long working hours and sleep-related problems on workers' safety among employers, workers, clients/customers, and the general public might be effective for preventing near-misses and injuries in industrial settings among workers, especially those who work long hours in the "transport/postal services" industry.

Abstract 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.

Objectives: Minimally invasive epiduroscopy has recently been reported as an effective treatment procedure for chronic and intractable low back pain. However, no study has determined safe anesthetics for monitored anesthesia care during epiduroscopy. We aimed to compare and evaluate conventional monitored anesthesia care drugs with dexmedetomidine. Methods: A retrospective study including all patients who underwent epiduroscopy at the JR Tokyo General Hospital from April 2011 to March 2016 was designed. The epiduroscopy procedures were performed under anesthesia with dexmedetomidine plus fentanyl (dexmedetomidine group) or droperidol plus fentanyl (neuroleptanalgesia group). Patients who received analgesics other than fentanyl, another analgesic combined with fentanyl, any sedative other than dexmedetomidine or droperidol, or who had incomplete data were excluded. We compared (1) the type and dose of medication during the epiduroscopy and (2) the incidence of postoperative nausea and vomiting. Results: We identified 45 patients (31 and 14 in the dexmedetomidine and neuroleptanalgesia groups, respectively) with a mean age of 69.0 years. The two groups had comparable characteristics, such as age, sex, body mass index, the American Society of Anesthesiologists Physical Status, analgesics used in the clinic, comorbidities, history of smoking, and the duration of anesthesia. The dexmedetomidine group received a significantly lower fentanyl dose during surgery (126 ± 14 vs 193 ± 21 µg, mean ± standard deviation, p = 0.014) and exhibited a significantly lower incidence of postoperative nausea and vomiting (1 vs 3, p = 0.047) than the neuroleptanalgesia group. Conclusion: This study involved elderly patients, and the use of dexmedetomidine in monitored anesthesia care during epiduroscopy procedures in these patients may reduce the required fentanyl dose during surgery and the incidence of postoperative nausea and vomiting. This strategy may help prevent respiratory depression and aspiration.

Background/Aim: Surgical resection is recommended for nonfunctional pancreatic neuroendocrine neoplasms (NFpNENs). However, metastasis is rare in patients with small lesions with histological grade 1 (G1); thus, observation is an optional treatment approach for small NF-pNENs. Texture analysis (TA) is an imaging analysis mode for quantification of heterogeneity by extracting quantitative parameters from images. We retrospectively evaluated the utility of TA in predicting histological grade of resected NF-pNENs in a multicenter retrospective study. Patients and Methods: The utility of TA in preoperative prediction of grade were evaluated with 29 patients treated by pancreatectomy for NF-pNEN who underwent preoperative dynamic computed tomography scan between January 1, 2013 and December 31, 2020 at three hospitals affiliated with the Jikei University School of Medicine. TA was performed with dedicated software for medical imaging processing for determining histological tumor grade using dynamic computed tomography images. Results: Histological tumor grades based on the 2017 World Health Organization Classification for Pancreatic Neuroendocrine Neoplasms were grade 1, 2 and 3 in 18, 10 and one patient, respectively. Preoperative grades by TA were 1 and 2/3 in 15 and 14 patients, respectively. The sensitivity, specificity and area under the curve for TA-oriented grade 1 lesions were 1.00, 0.889 and 0.965 (95% confidence interval=0.901-1.000), respectively. Conclusion: TA is useful for predicting grade 2/3 NF-pNEN and can provide a safe option for observation for patients with small grade 1 lesions. [ABSTRACT FROM AUTHOR]