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This paper reports on gas sensing based on near-infrared (NIR) reconstructive spectroscopy using a surface plasmon resonance (SPR) photodetector. The reconstructive spectrometer consists of an Au g...

Background: The relationship between advance care planning and religious beliefs, which are important for palliative care, is controversial in Western countries and has not been verified in Asian countries. Aim: To investigate the association between advance care planning discussions and religious beliefs in Japan. Design: A nationwide survey conducted in 2016 using a quota sampling method to obtain a representative sample of Japan’s general population. Setting/participants: We analyzed responses from 3167 adults aged 20–84 years (mean age ± standard deviation, 50.9 ± 16.8 years). The outcome was measured by asking whether the respondents had ever discussed advance care planning, and the main exposure by whether they had any religious beliefs or affiliations, and if so, their degree of devoutness. We analyzed religious beliefs, affiliations, and devoutness in relation to the occurrence of discussions using multivariable logistic regression models adjusted for possible sociodemographic covariates. Results: Compared with respondents without, those with religious beliefs had significantly higher odds of having had discussions (adjusted odds ratio: 1.45, 95% confidence interval: 1.22–1.73). The devoutness of religious belief was proportional to the propensity of the occurrence of discussions ( p for trend < 0.001). In addition, Buddhists and Christians had higher odds of having had discussions than did nonbelievers. Conclusion: The results suggest that holding religious beliefs, especially in Japanese Buddhism and Christianity, facilitates advance care planning discussions among Japanese adults, and thus, may help health-care providers identify those prioritized for facilitating engagement in advance care planning, especially in palliative and spiritual care settings.

New 4,8,12-trioxotriangulene (TOT) neutral radical derivatives having three methoxy and hydroxy groups at the α-positions were synthesized, and the substituent effects on the electronic spin and redox properties were elucidated in the theoretical and experimental methods. Due to the small SOMO coefficients at the α-positions of TOT, the methoxy groups in the TOT neutral radical had negligible effects on the electronic spin structure and redox ability. On the other hand, methoxy groups greatly increased the LUMO energy having large coefficients at α-positions and, thus, caused a remarkable negative-potential shift of the redox wave of anion species involving the dianion and trianion species. Converting the methoxy groups to hydroxy groups caused a dramatic change in the electronic structure of TOT, where the intramolecular hydrogen bonds between hydroxy groups and oxo groups strongly attracted a minus charge on the TOT skeleton. The HOMO energy of the monoanion species was significantly reduced, causing a blue shift of the HOMO-LUMO transition and an anodic shift of the redox potential. In addition, due to the steric repulsion smaller than that of the methoxy group, the hydroxy derivative showed a more planar molecular structure and a strong π-stacking ability.

Primary tumor resection (PTR) before commencing systemic chemotherapy in patients with stage IV colorectal cancer and unresectable metastases (mCRC) remains controversial. This study aimed to assess whether PTR before systemic chemotherapy is associated with mortality in mCRC patients, after adjusting for confounding factors, such as the severity of the primary tumor and metastatic lesions. We analyzed hospital-based cancer registries from nine designated cancer hospitals in Fukushima Prefecture, Japan. Patients were divided into two groups (PTR and non-PTR), based on whether PTR was performed as initial therapy for mCRC or not. The primary outcome was all-cause mortality. Kaplan–Meier survival analysis was performed, and survival estimates were compared using the log-rank test. Adjusted hazard ratios were calculated using Cox regression to adjust for confounding factors. All tests were two-sided; P-values

Introduction Helicobacter pylori eradication therapy requires a complex prescribing schedule combining clarithromycin, amoxicillin, and a proton-pump inhibitor (PPI) or potassium-competitive acid blocker (P-CAB, vonoprazan). To reduce the burden of complex prescribing and increase adherence, a vonoprazan triple-drug blister pack comprising all three medications was launched in June 2016. This study aimed to assess the impact of the combination blister pack on eradication success rate in Japan immediately after launch. Methods We performed an interrupted time series analysis using a large administrative claims database of 7,300,000 insured individuals. We identified 36,570 patients who received first-line clarithromycin triple therapy from June 2015 to May 2016 (prelaunch) and 35,721 who received the same therapy from July 2016 to June 2017 (post-launch). The primary outcome was the success rate of clarithromycin triple therapy and the secondary outcomes were proportion of vonoprazan use and proportion of combination blister pack use. Results The success rate of clarithromycin triple therapy increased by 2.44% (95% confidence interval [CI] 1.36–3.52; P

Skeletal muscle atrophy often complicates idiopathic pulmonary fibrosis (IPF). IPF patients frequently experience acute exacerbation (AE), but the association between skeletal muscle atrophy and mortality remains unknown in AE-IPF patients. Herein, cross-sectional areas of the erector spinae muscle (ESMCSA) and the pectoralis muscle (PMCSA) of AE-IPF patients were analysed via computed tomography. Primary outcome was 90-day mortality. Survival probability was estimated using the Kaplan–Meier method, and the log-rank test was used between the low and high groups of ESMCSA and PMCSA. We used multivariable Cox proportional-hazards models to evaluate the association between ESMCSA and PMCSA and prognosis. Among the 212 patients, 94 (44%) died during the observation period. The low ESMCSA group (2) had a significantly worse prognosis than the high group (≥ 25.6 cm2) (hazard ratio (HR) [95% confidence interval (CI)]: 1.52 [1.00–2.33], p = 0.049). Multivariable analyses showed that all-cause mortality was associated with low ESMCSA (model 1, adjusted HR [95% CI]: 1.59 [0.98–2.60]; model 2, 1.55 [0.95–2.56] and model 3, 1.67 [1.00–2.78]). A similar trend was observed between low PMCSA and poor prognosis (HR [95% CI]: 1.39 [0.88–2.20]). In conclusion, low ESMCSA is associated with high 90-day mortality in AE-IPF patients.

ObjectiveAlthough mindfulness and self-compassion programs have been applied in clinical settings, no studies have reported their benefits for atopic dermatitis (AD). The aim of the study was to evaluate the feasibility and acceptability of an online group format of 8 weekly 90-minute sessions of a mindfulness and self-compassion program for adults with AD.ResultsIn this single-arm, open label pre-post comparison study design, 15 adults (10 women; mean age, 38.3 ± 8.98 years) completed the intervention and assessment. The primary outcome was disease-specific quality of life (QOL) (Dermatology Life Quality Index and Skindex-16) at the 20-week follow-up. The secondary outcomes were other self-reported questionnaires, and descriptive feedback of the program. Assessments were conducted at baseline, mid-treatment, post-intervention, and at follow-up. Overall, there were no significant improvements. However, of the four participants whose QOL was largely impacted due to AD, the scores improved significantly, with minimal clinically important difference or greater change. All participants were satisfied with the program. This program could benefit adults with AD by improving QOL. Randomized controlled trials are warranted to elucidate the efficacy of the program. This study has been registered at the UMIN Clinical Trials Registry (ID: UMIN000030484).

To investigate whether lower limb arterial calcification (LLAC) quantified using computed tomography (CT) was a risk factor for bilateral severe knee osteoarthritis (OA).This cross-sectional study included patients who were scheduled for surgical treatment of primary varus knee OA. Knee OA was evaluated using the Kellgren-Lawrence (KL) classification, KL grades 3 and 4 were defined as severe OA. The LLAC score in the bilateral whole leg CT was quantitatively measured and categorized into low or high groups based on the median value. A modified Poisson regression model was used to examine the relationship between the categorized LLAC score and the presence of bilateral severe knee OA with adjustment for possible confounders.Of a total of 252 patients examined, multivariable modified Poisson regression analysis showed a significant association between higher LLAC score and the presence of bilateral severe knee OA (adjusted risk ratio = 1.28; 95% confidence interval [CI], 1.12-1.48;LLAC was associated with bilateral severe knee OA, and the LLAC score may be a useful measurement to identify patients at risk of bilateral severe knee OA.

Context Advance care planning (ACP) is vital for end-of-life care management. Experiences as informal family caregivers might act as a catalyst to promote ACP. Objectives We investigated the association between ACP discussions and caregiving experiences. Methods A nationwide survey in Japan was conducted in December 2016 using a quota sampling method to select a sample representative of the general Japanese population. The responses of 3167 individuals aged 20–84 years (mean age: 50.9 ± 16.8) were analyzed. The outcome was measured by asking if respondents had ever engaged in ACP discussions. The exposure was measured by asking whether and for how long respondents had experience as informal caregivers for family members. We analyzed informal caregiving experience related to the occurrence of ACP discussions using multivariable logistic regression models that adjusted for possible covariates. Results Respondents with informal caregiving experience had significantly higher odds of having ACP discussions than those without caregiving experience (adjusted odds ratio: 1.93, 95% CI = 1.63, 2.29). Stronger effects were identified in younger adults (aged 20–65 years) and those with a higher education level (education duration > 12 years) than in older adults (aged ≥65 years) and those with a lower education level, respectively. Conclusion Experiences as informal caregivers for family members may facilitate ACP discussions among Japanese adults, especially younger adults with higher educational attainment. Our findings may help health-care providers screen those at risk for inadequate ACP discussions, and informal caregiving experience should be considered when health-care providers initiate discussions of end-of-life care.

A conceptual framework for advance care planning is lacking in societies like Japan's valuing family-centered decision-making.A consensus definition of advance care planning with action guideline adapted to Japanese society.We conducted a multidisciplinary modified Delphi study 2020-2022. Thirty physicians, 10 healthcare and bioethics researchers, six nurses, three patient care managers, three medical social workers, three law experts, and a chaplain evaluated, in 7 rounds (including two web-based surveys where the consensus level was defined as ratings by ≥70% of panelists of 7-9 on a nine-point Likert scale), brief sentences delineating the definition, scope, subjects, and action guideline for advance care planning in Japan.The resulting 29-item set attained the target consensus level, with 72%-96% of item ratings 7-9. Advance care planning was defined as "an individual's thinking about and discussing with their family and other people close to them, with the support as necessary of healthcare providers who have established a trusting relationship with them, preparations for the future, including the way of life and medical treatment and care that they wish to have in the future." This definition/action guideline specifically included support for individuals hesitant to express opinions to develop and express preparations for the future.Adaptation of advance care planning to Japanese culture by consciously enhancing and supporting individuals' autonomous decision-making may facilitate its spread and establishment in Japan and other societies with family-centered decision-making cultures.

Fat accumulation in the liver, pancreas, skeletal muscle, and visceral bed relates to type-2 diabetes (T2D). However, the distribution of fat among these compartments is heterogenous and it is unclear whether specific distribution patterns indicate high T2D risk. We therefore investigated fat-distribution patterns and their link to future T2D. From 2168 individuals without diabetes who underwent computed tomography in Japan, this case-cohort study included 658 randomly selected individuals and 146 incident cases of T2D over 6 years of follow-up. Using data-driven analysis (k-means) based on fat content in the liver, pancreas, muscle, and visceral bed, we identified four fat-distribution clusters: Hepatic steatosis, Pancreatic steatosis, Trunk myosteatosis, and Steatopenia. Compared with the Steatopenia cluster, the adjusted hazard ratios (95% CIs) for incident T2D were 4.02 (2.27-7.12) for the Hepatic steatosis cluster, 3.38 (1.65-6.91) for the Pancreatic steatosis cluster, and 1.95 (1.07-3.54) for the Trunk myosteatosis cluster. The clusters were replicated in 319 German individuals without diabetes who underwent magnetic resonance imaging and metabolic phenotyping. The distribution of AUC-glucose across the four clusters found in Germany was similar to the distribution of T2D risk across the four clusters in Japan. Insulin sensitivity and insulin secretion differed across the four clusters. Thus, we identified patterns of fat distribution with different T2D risks presumably due to differences in insulin sensitivity and insulin secretion.

Objective: Fat accumulation in liver, pancreas, skeletal muscle, and visceral bed relates to type 2 diabetes (T2D) . However, distribution of fat in these compartments is heterogenous and it is unclear if specific distribution patterns indicate high T2D risk. We therefore investigated fat distribution patterns and their link to future T2D. Methods: From 2168 individuals without diabetes undergoing computed tomography in Japan, this case-cohort study included 658 randomly selected individuals and 146 incident cases of T2D with a 6-year follow-up. Data-driven analysis (k-means) was applied to develop clusters based on fat content in liver, pancreas, muscle, and visceral bed. Hazard ratios (HRs) for association of clusters and incident T2D were estimated using weighted Cox regression. In 3 individuals without diabetes with magnetic resonance imaging and metabolic phenotyping in Germany, cluster validation with additional assessment of glycemic traits from OGTTs was conducted. Results: We identified four clusters of fat distribution: cluster 1 (Hepatic steatosis cluster) , cluster 2 (Pancreatic steatosis cluster) , cluster 3 (Myosteatosis dominant cluster) , cluster 4 (Steatopenic cluster) . Compared with Steatopenic cluster, the adjusted-HRs (95%CIs) for incident T2D were 4.02 (2.27-7.12) in Hepatic steatosis cluster, 3.38 (1.65-6.91) in Pancreatic steatosis cluster, and 1.95 (1.07-3.54) in Myosteatosis dominant cluster. The clusters were replicated in the German cohort with similar distribution of AUC-glucose to the diabetes hazard in the Japanese cohort. Insulin sensitivity and insulin secretion were different across clusters with the lowest insulin sensitivity and highest insulin secretion in Hepatic steatosis cluster. Conclusions: Extending evidence about fat accumulation in single compartments, we identified specific patterns of fat distribution with different T2D risk presumably due to differences in insulin sensitivity and insulin secretion. Disclosure H.Yamazaki: None. N.Stefan: Advisory Panel; Gilead Sciences, Inc., GlaxoSmithKline plc., Sanofi, Consultant; AstraZeneca, Intercept Pharmaceuticals, Inc., Novo Nordisk, Pfizer Inc., Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Merck Sharp & Dohme Corp. A.Fritsche: Advisory Panel; Boehringer Ingelheim International GmbH, Novo Nordisk, Sanofi-Aventis Deutschland GmbH. A.L.Birkenfeld: None. R.Wagner: Advisory Panel; Akcea Therapeutics, Daiichi Sankyo, Sanofi-Aventis Deutschland GmbH, Speaker's Bureau; Lilly, Novo Nordisk, Sanofi-Aventis Deutschland GmbH. M.Heni: Advisory Panel; Boehringer Ingelheim International GmbH, Research Support; Boehringer Ingelheim International GmbH, Sanofi, Speaker's Bureau; Amryt Pharma Plc, Boehringer Ingelheim International GmbH, Novo Nordisk. S.Tauchi: None. J.Machann: None. T.Haueise: None. Y.Yamamoto: None. M.Dohke: None. N.Hanawa: None. Y.Kodama: Other Relationship; Eisai Co., Ltd. A.Katanuma: None. Funding the German Center for Diabetes Research (DZD, 01GI0925) , the state of Baden-Württemberg (32-5400/58/2, Forum Gesundheitsstandort Baden-Württemberg) , and JSPS KAKENHI Grant Number 19K16978

BackgroundData on the effects of intraoperative end-tidal carbon dioxide (EtCO2) levels on postoperative organ dysfunction are limited. Thus, this study was designed to investigate the relationship between the intraoperative EtCO2 level and postoperative organ dysfunction in patients who underwent major abdominal surgery under general anesthesia.MethodsWe conducted a retrospective cohort study involving patients who underwent major abdominal surgery under general anesthesia at Kyoto University Hospital. We classified those with a mean EtCO2 of less than 35 mmHg as low EtCO2. The time effect was determined as the minutes when the EtCO2 value was below 35 mmHg, whereas the cumulative effect was evaluated by measuring the area below the 35-mmHg threshold. The outcome was postoperative organ dysfunction, defined as a composite of at least one organ dysfunction among acute renal injury, circulatory dysfunction, respiratory dysfunction, coagulation dysfunction, and liver dysfunction within 7 days after surgery.ResultsOf the 4,171 patients, 1,195 (28%) had low EtCO2, and 1,428 (34%) had postoperative organ dysfunction. An association was found between low EtCO2 and increased postoperative organ dysfunction (adjusted risk ratio, 1.11; 95% confidence interval [CI], 1.03–1.20; p = 0.006). Additionally, long-term exposure to EtCO2 values of less than 35 mmHg (≥224 min) was associated with postoperative organ dysfunction (adjusted risk ratio, 1.18; 95% CI, 1.06–1.32; p = 0.003) and low EtCO2 severity (area under the threshold) (adjusted risk ratio, 1.13; 95% CI, 1.02–1.26; p = 0.018).ConclusionsIntraoperative low EtCO2 of below 35 mmHg was associated with increased postoperative organ dysfunction.

Purpose Healthy lifestyle is related to quality of life (QOL) after cancer diagnosis and prognosis. However, there are few reports on patients conscious of healthy lifestyle and patients requiring medical providers’ attention regarding healthy lifestyle. We aimed to develop a healthy lifestyle consciousness index (HLCI) for cancer patients and evaluated its validity in gynecological cancer patients. Methods The HLCI was designed to assess degree of healthy lifestyle consciousness, including items regarding “diet,” “exercise,” “body weight,” and “sleep.” Exploratory factor analysis was performed for dimensionality of the scale; Cronbach’s alpha was calculated to assess internal-consistency reliability. For criterion-based validity, we calculated proportions of stage III/IV gynecological malignancies in those with categorized HLCI scores based on tertiles. Concurrent validity was evaluated between HLCI and other quality of life (QOL) scales including European Organization for Research and Treatment of Cancer QLQ-C30 in limited patients. Results HLCI comprised five 10-point items (0–45); higher values implied improved healthy lifestyle consciousness. Data from 108 gynecological malignancy patients at Kyoto University Hospital were analyzed. The mean age of subjects was 55.8 years; 36.1% of them had uterine corpus cancer; 34.3% were at stage III/IV of gynecological malignancy. The factor analysis revealed HLCI was unidimensional; the reliability based on Cronbach’s alpha was satisfactory (0.88). The proportions of stage III/IV gynecological malignancies were 25.7%, 33.3%, and 44.4% in those with first (7–24 points), second (25–30 points), and third (31–46 points) tertiles of HLCI score, respectively. For patients with other QOL scales (n = 25), the mean scores of global health status of QLQ-C30 were 33.3, 50.0, and 83.3 for first, second, and third tertiles of HLCI score, respectively. Conclusion HLCI was successfully validated; thus, patients with advanced stages or higher QOL might have strong consciousness regarding healthy lifestyle. HLCI may be useful in precision care for improved lifestyles and QOL.

Objectives:To assess the impact of nationwide outpatient antimicrobial stewardship interventions in the form of financial incentives for providers and provider education when antimicrobials are deemed unnecessary for uncomplicated respiratory infections and acute diarrhea.Methods:We collected data from a large claims database from April 2013 through March 2020 and performed a quasi-experimental, interrupted time-series analysis. The outcome of interest was oral antimicrobial prescription rate defined as the number of monthly antimicrobial prescriptions divided by the number of outpatient visits each month. We examined the effects of financial incentive to providers (ie, targeted prescriptions for those aged ≤2 years) and provider education (ie, targeted prescriptions for those aged ≥6 years) on the overall antimicrobial prescription rates and how these interventions affected different age groups before and after their implementation.Results:In total, 21,647,080 oral antimicrobials were prescribed to 2,920,381 unique outpatients during the study period. At baseline, prescription rates for all age groups followed a downward trend throughout the study period. Immediately after the financial incentive implementation, substantial reductions in prescription rates were observed among only those aged 0–2 years (−47.5 prescriptions per 1,000 clinic visits each month; 95% confidence interval, −77.3 to −17.6; P = .003), whereas provider education immediately reduced prescription rates in all age groups uniformly. These interventions did not affect the long-term trend for any age group.Conclusion:These results suggest that the nationwide implementation of financial incentives and provider education had an immediate effect on the antimicrobial prescription but no long-term effect.

Aim There is growing recognition of the need to hold advance care planning discussions. Older adults who have direct interpersonal involvement with dying family members might begin to consider their own end-of-life care. This study examined the associations between experiences of being with a dying family member and advance care planning discussions among Japanese older adults. Methods This study examined data from a previous self-administered questionnaire survey carried out among outpatients aged ≥65 years. All participants were visitors of a community hospital in Japan, with data being collected over a 1-week period in July 2016. The main exposure was experiences of being with dying family members, while the outcome was advance care planning discussions with the family members and/or their physician. We analyzed the associations between experiences of being with dying family members and advance care planning discussions through log-binomial regression models adjusted for possible sociodemographic confounders. Results Of the 302 respondents included for analysis, 96 (32%) had experiences of being with dying family members, while 179 (59%) held advance care planning discussions. Respondents with said experiences were more likely to have discussions than those without experiences (fully adjusted prevalence ratio 1.31, 95% confidence interval 1.04-1.65). Subgroup analyses showed no significant interaction effects between experiences of being with dying family members and the covariates. Conclusions Direct interpersonal involvement with dying family members might facilitate advance care planning discussions among Japanese older adults. Our results should help healthcare providers recognize individuals who are unlikely to have discussions. Geriatr Gerontol Int 2021; 21: 197-202.

Background Although hospitalized patients with acute decompensated heart failure (ADHF) have severe physical dysfunction, little data are available on the comparative effectiveness of early versus late rehabilitation. This study examined the relationship between early compared to late rehabilitation and physical function among older patients hospitalized for ADHF. Methods In a retrospective cohort study, independent patients aged ≥65 years at baseline who were hospitalized for ADHF from 2012 to 2014 and underwent inpatient rehabilitation were identified using Emergency Department visit data and electronic medical records at two hospitals. Patients were classified into those who underwent early rehabilitation (initiated within 72 hours of admission) and late rehabilitation (after 72 hours). Primary outcome was length of time from admission until the patient was able to walk independently. Multivariable competing-risk regression with death as the competing event was used to adjust for potential confounding factors, and multiple imputation (MI) analysis was performed. Results Of 259 individuals, 30 (11.6%) commenced rehabilitation within 72 hours after admission while 229 (88.4%) did so 72 hours after admission. Patients who received early rehabilitation had a higher rate of unassisted walking for at least 40 m by 30 days after admission (hazard ratio: 8.03; 95% confidence interval: 2.15 to 29.98; P = .002 in the multivariable adjusted model) than those who received late rehabilitation. Similar findings were observed on MI analysis. Conclusion Early rehabilitation therapy commenced within 72 hours of admission was associated with a higher rate of recovery of an activity of daily living (independent walking on a level surface).

Background: To evaluate the diagnostic accuracy and clinical utility of the acute aortic dissection detection risk score (ADD-RS) alone or with D-dimer as a screening test to exclude acute aortic syndrome. Methods: We conducted a systematic review and meta-analysis of studies examining the diagnostic accuracy of ADD-RS. We searched MEDLINE, Embase and Cochrane Controlled Register of Trials up to 12 December 2018. Results: We identified nine studies involving 26,598 patients for ADD-RS alone and 3421 patients with D-dimer. Overall, the methodological quality based on the Quality Assessment of Diagnostic Accuracy Studies 2 was moderate to high. Bivariate meta-analyses showed that the pooled sensitivities were 0.94 (95% confidence interval (CI) 0.90, 0.96) at the threshold of ADD-RS ≥1, 0.46 (95% CI, 0.34, 0.59) at ADD-RS ≥2, 1.00 (95% CI 0.99, 1.00) at ADD-RS ≥1 with D-dimer and 0.99 (95% CI 0.97, 1.00) at ADD-RS ≥2 with D-dimer. For the low prevalence population, failure rate and efficiency were 0.8% and 38.3% at ADD-RS ≥1, 0.03% and 14.5% at ADD-RS ≥1 with D-dimer, and 0.1% and 33.6% at ADD-RS ≥2 with D-dimer, respectively. For the high prevalence population, failure rate and efficiency were 3.8% and 33.3% at ADD-RS ≥1, 0.2% and 12.3% at ADD-RS ≥1 with D-dimer and 0.6% and 28.4% at ADD-RS ≥2 with D-dimer, respectively. Conclusions: ADD-RS alone or with D-dimer was a useful screening test with high sensitivity to exclude acute aortic syndrome. However, the optimal threshold of ADD-RS alone or with D-dimer may depend on the clinical setting.

Introduction Although predialysis hemoglobin concentration is affected by interdialytic weight gain (IDWG), the interaction between these parameters is not well understood. Methods Using data from the Dialysis Outcomes and Practice Pattern Study in Japan (J-DOPPS) phases 1, 2, 3, 4, and 5, we analyzed patients who underwent maintenance hemodialysis. The exposure variable was hemoglobin concentration, and the effect modifier was IDWG at baseline. These 2 categorical variables were then combined and analyzed. The primary outcome was major adverse cardiovascular events (MACEs). Hazard ratios (HRs) were estimated using a Cox model for the association between exposure and MACEs after adjusting for potential confounders. We examined additive interactions between hemoglobin concentration and IDWG by calculating the relative excess risk due to interaction (RERI), which is defined as a departure from the additivity of effects. Results A total of 8234 patients were enrolled. During a median follow-up of 2.1 years, 1062 (12.9%) patients developed MACEs. As the IDWG increased, the lowest point estimation in each IDWG category tended to shift to the lower hemoglobin concentration categories. In IDWG categories of ≥6%, point estimation of MACEs with hemoglobin concentration of ≥10.0 g/dl to, Graphical abstract

We used 2‐D shear wave elastography to quantify lymph node hardness, from the shear wave velocity, to determine the presence or absence of metastatic lymphadenopathy in the inguinal lymph nodes of five patients with malignant melanoma and squamous cell carcinoma. The shear wave velocity accurately identified all cases of metastasis confirmed by histology, compared with two false‐positive and one false‐negative finding with positron emission tomography/computed tomography. 2‐D shear wave elastography would be useful to evaluate inguinal lymph node metastasis.

BACKGROUND Taxanes are the current first-line treatment for advanced cutaneous angiosarcoma (CAS) for patients who are considered difficult to treat with doxorubicin owing to advanced age or comorbidity. However, no effective second-line therapy for such patients has been established. METHODS We designed a single-arm prospective observational study of eribulin mesylate (ERB) administered at a dose of 1·4 mg m-2 on days 1 and 8 in a 21-day cycle. Patients with advanced CAS who were previously treated with a taxane and were scheduled to begin ERB treatment were enrolled. The primary endpoint was overall survival (OS) and the secondary endpoints were response rate (RR), progression-free survival (PFS) and toxicity assessment. RESULTS We enrolled a total of 25 patients. The median OS and PFS were 8·6 months and 3·0 months, respectively. The best overall RR was 20% (five of 25). In total, 16 grade 3/4 severe adverse events (SAEs) occurred; however, all patients recovered. Patients who achieved partial response or stable disease as best response had longer OS than those with progressive disease (median OS not reached and 3·3 months, respectively; P < 0·001). Patients who did not experience SAEs showed longer OS than those who did (median OS 18·8 months and 7·5 months, respectively; P < 0·05). Patients with distant metastasis had shorter median OS than those with locoregional disease, but without statistically significant difference. CONCLUSIONS ERB showed a promising RR and is a potential candidate for second-line treatment for patients with CAS, after treatment with taxanes. However, owing to the occurrence of SAEs in over half of the participants, caution should be exercised regarding ERB use in elderly patients. What is already known about this topic? Taxanes are the current first-line treatment for patients with advanced cutaneous angiosarcoma (CAS) who are considered difficult to treat with doxorubicin owing to advanced age or comorbidity. No effective therapy for taxane-resistant CAS has been established thus far. Eribulin suppresses microtubule polymerization and elicits an antitumour effect similar to that of taxanes. What does this study add? In our single-arm prospective observational study to evaluate the efficacy of eribulin for treating patients with advanced CAS who previously received taxanes, the median overall survival and progression-free survival were 8·6 and 3·0 months, respectively. Response rates at weeks 7, 13 and 25 were 20%, 17% and 14%, respectively. Although 16 grade 3/4 severe adverse events occurred, all patients recovered. Eribulin showed a promising response rate and is a potential candidate for second-line treatment in CAS after taxane treatment. Linked Comment: Smrke and Benson. Br J Dermatol 2020; 183:797-798.

Background: Although advance care planning discussions are increasingly accepted worldwide, their ideal timing is uncertain and cultural factors may pertain. Aim: To evaluate timing and factors affecting initiation of advance care planning discussions for adult patients in Japan and Taiwan. Design: Mixed-methods questionnaire survey to quantitatively determine percentages of patients willing to initiate advance care planning discussions at four stages of illness trajectory ranging from healthy to undeniably ill, and to identify qualitative perceptions underlying preferred timing. Setting/participants: Patients aged 40–75 years visiting outpatient departments at four Japanese and two Taiwanese hospitals were randomly recruited. Results: Overall (of 700 respondents), 72% (of 365) in Japan and 84% (of 335) in Taiwan ( p Conclusion: The majority of patients are willing to begin discussion before their health is severely compromised; about one out of five patients are unwilling to begin until clearly facing death. To promote advance care planning, healthcare providers must be mindful of patients’ preferences and factors associated with acceptance and reluctance to initiate advance care planning.

Only a few studies have longitudinally evaluated whether fatty pancreas increases the risk of type-2 diabetes (T2D), and their results were inconsistent. Fatty pancreas is closely linked to overweight and obesity, but previous studies did not exclude overweight or obese individuals. Therefore, in this cohort study, we investigated the association between fatty pancreas and T2D incidence in lean individuals. Between 2008 and 2013, 1478 nondiabetic lean individuals (i.e. body-mass index

Objective This study aimed to evaluate the influence of advanced glycation end-product (AGE) accumulation on the prevalence and severity of overactive bladder (OAB) in community-dwelling elderly adults. Methods We conducted a cross-sectional study involving 269 Japanese community dwellers aged ≥75 years in 2015. AGE accumulation was non-invasively measured via skin autofluorescence (SAF) values using AGE Reader. The primary and secondary outcomes were the presence and severity of OAB evaluated using the Overactive Bladder Symptom Score (OABSS). Individuals with an urgency score of ≥2 and sum score of ≥3 were considered to have OAB. The associations of SAF with the prevalence and severity of OAB were assessed using logistic and linear regression models, respectively, adjusted for clinically important confounders. Results The median age of participants was 78 years. Of 269 participants, 110 (40.9%) were men and 75 (27.9%) had OAB. The median SAF was 2.2 AU (arbitrary units). Increasing median SAF was observed with increasing age. Multivariable analysis revealed that SAF was not associated with either the likelihood of having OAB (odds ratio per 1 AU = 0.77, 95% confidence interval: 0.37–1.62) or the natural log-transformed OABSS (β per 1 AU = −0.07, 95% confidence interval: −0.26–0.12). Conclusions In this study, AGE accumulation, as assessed by SAF, was not associated with the prevalence and severity of OAB in Japanese community-dwelling elderly people aged ≥75 years.

Background: Early detection of cognitive decline allows timely intervention to delay progression of dementia. However, current cognitive evaluation tools often include items delivered via verbal forms of instruction, which can cause poor performance in patients with hearing loss. Objective: To develop and validate a cognitive screening battery, the Reading Cognitive Test Kyoto (ReaCT Kyoto), comprising test items given through non-verbal instruction. Methods: A cross-sectional and multi-center study was conducted in the three medical institutes. ReaCT Kyoto was designed to evaluate domains of “registration,” “repetition,” “delayed recall,” “visuospatial recognition,” “orientation in time and place,” and “executive function.” The Japanese version of the Mini-Mental State Examination Test (MMSE-J) and ReaCT Kyoto were applied by experienced psychotherapists. Concurrent validity was evaluated between the ReaCT Kyoto Test and MMSE-J and between the ReaCT Kyoto Test and physician-diagnosed dementia. Results: ReaCT Kyoto was validated in a sample of 115 participants. The mean age of subjects was 81.0±6.4 years, and the sample comprised 53.0% females. The area under the receiver operating curves was 0.95 for detecting physician-diagnosed dementia. When classifying patients in accordance with presence or absence of hearing loss, the AUCs were 0.93 and 0.97 for those with and without hearing loss, respectively. With a cut-off score of

Introduction: Patients undergoing hemodialysis (HD) have higher predialysis plasma osmolality. Several studies have suggested lower osmolality to be associated with worse outcomes in patients not undergoing HD. However, no studies have examined the association between osmolality and mortality among patients undergoing HD. Objective: We aimed to examine the association between predialysis plasma calculated osmolality and all-cause mortality. Methods: This was a prospective cohort study of 1,240 patients undergoing HD participating in the Japanese Dialysis Outcomes and Practice Patterns Study phase 5 (2012–2015). The exposure was predialysis plasma osmolality, calculated as 2 × (serum sodium concentration [mmol/L]) + (serum urea nitrogen [mg/dL])/2.8 + (serum glucose [mg/dL])/18. The primary outcome was all-cause mortality. The secondary outcome was the change in systolic blood pressure (SBP) during HD. We used a marginal structural model with stabilized weights to estimate the association between calculated osmolality and all-cause mortality in the presence of time-varying confounders affected by prior exposure. Results: Mean baseline plasma calculated osmolality was 306.8 ± 8.6 mOsm/kg. Low predialysis calculated osmolality was associated with higher mortality (adjusted hazard ratio 1.52, 95% confidence interval [CI]: 1.30–1.78 by each 10 mOsm/L lower osmolality). The association was consistent across clinically relevant subgroups. Predialysis osmolality was significantly associated with intradialytic SBP change (mean difference 0.96 [95% CI: 0.05–1.88] mm Hg per each 10 mOsm/L lower osmolality). Conclusions: Low predialysis calculated osmolality was an independent risk factor of all-cause mortality.

Malignant melanomas often present with irregular shapes and in multiple shades of brown under white light. Dermoscopy is used to diagnose malignant melanomas; nevertheless, it is often difficult to differentiate malignant melanoma from healthy pigmented skin. The DZ-D100 dermoscope (Casio Computer) is a digital camera equipped with a white light-emitting diode (LED) and a violet LED, which can capture non-polarized/polarized conventional dermoscopy images (CDS) as well as violet-light dermoscopy (VLD) images. Since the absorption wavelength of melanin approaches that of ultraviolet rays, VLD with a wavelength of 405 nm can be used to visualize it. This camera allows three images with the same composition to be captured simultaneously. In this case, we performed dermoscopy with DZ-D100 to determine the surgical resection margins of a melanoma of the heel in a 76-year-old woman. The pale-colored lesions that were difficult to demarcate by CDS were clearly visible by VLD, presenting as dark areas in the grayscale images. Preoperatively determined lesion boundaries with CDS in combination with VLD were histologically more accurate than those with conventional CDS alone. Therefore, the combination of CDS and VLD may reveal the distribution of subtle pigmentation of fine melanin in the skin, making it easier to distinguish between lesions and healthy skin. As one of the limitations, parts of the heel with thick stratum corneum were also observed to be dark gray in the VLD images. Therefore, the evaluation of pigment lesion should be performed by comparing both CDS and VLD.

ObjectivesThis study aimed to investigate the association between kyphotic posture and future loss of independence (LOI) and mortality in community-dwelling older adults.DesignProspective cohort study.SettingTwo Japanese municipalities.ParticipantsWe enrolled 2193 independent community-dwelling older adults aged≥65 years at the time of their baseline health check-up in 2008. Kyphotic posture was evaluated using the wall-occiput test (WOT) and classified into three categories: non-kyphotic, mild (>0 and ≤4 cm) and severe (>4 cm).Primary and secondary outcome measuresThe primary outcome was mortality and the secondary outcomes were LOI (new long-term care insurance certification levels 1–5) and a composite of LOI and mortality. A Cox proportional hazards model was used to estimate the adjusted HRs (aHRs).ResultsOf the 2193 subjects enrolled, 1621 were included in the primary analysis. Among these, 272 (17%) and 202 (12%) were diagnosed with mild and severe kyphotic postures, respectively. The median follow-up time was 5.8 years. Compared with the non-kyphotic group, the aHRs for mortality were 1.17 (95% CI 0.70 to 1.96) and 1.99 (95% CI 1.20 to 3.30) in the mild and severe kyphotic posture groups, respectively. In the secondary analysis, a consistent association was observed for LOI (mild: aHR 1.70, 95% CI 1.13 to 2.55; severe: aHR 2.08, 95% CI 1.39 to 3.10) and the LOI-mortality composite (mild: aHR 1.27, 95% CI 0.90 to 1.79; severe: aHR 1.83, 95% CI 1.31 to 2.56).ConclusionKyphotic posture was associated with LOI and mortality in community-dwelling older adults. Identifying the population with kyphotic posture using the WOT might help improve community health.

Diminishing homeostatic proliferation of memory T cells is essential for improving the efficacy of lymphoablation in transplant recipients. Our previous studies in a mouse heart transplantation model established that B lymphocytes secreting proinflammatory cytokines are critical for T cell recovery after lymphoablation. The goal of the current study was to identify mediators of B cell activation following lymphoablation in allograft recipients. Transcriptome analysis revealed that macrophage-inducible C-type lectin (Mincle, Clec4e) expression is up-regulated in B cells from heart allograft recipients treated with murine anti-thymocyte globulin (mATG). Recipient Mincle deficiency diminishes B cell production of pro-inflammatory cytokines and impairs T lymphocyte reconstitution. Mixed bone marrow chimeras lacking Mincle only in B lymphocytes have similar defects in T cell recovery. Conversely, treatment with a synthetic Mincle ligand enhances T cell reconstitution after lymphoablation in non-transplanted mice. Treatment with agonistic CD40 mAb facilitates T cell reconstitution in CD4 T cell-depleted, but not in Mincle-deficient, recipients indicating that CD40 signaling induces T cell proliferation via a Mincle-dependent pathway. These findings are the first to identify an important function of B cell Mincle as a sensor of damage-associated molecular patterns released by the graft and demonstrate its role in clinically relevant settings of organ transplantation.

Aims To develop and internally validate a preoperative clinical prediction model for acute adjacent vertebral fracture (AVF) after vertebral augmentation to support preoperative decision-making, named the after vertebral augmentation (AVA) score. Methods In this prognostic study, a multicentre, retrospective single-level vertebral augmentation cohort of 377 patients from six Japanese hospitals was used to derive an AVF prediction model. Backward stepwise selection (p < 0.05) was used to select preoperative clinical and imaging predictors for acute AVF after vertebral augmentation for up to one month, from 14 predictors. We assigned a score to each selected variable based on the regression coefficient and developed the AVA scoring system. We evaluated sensitivity and specificity for each cut-off, area under the curve (AUC), and calibration as diagnostic performance. Internal validation was conducted using bootstrapping to correct the optimism. Results Of the 377 patients used for model derivation, 58 (15%) had an acute AVF postoperatively. The following preoperative measures on multivariable analysis were summarized in the five-point AVA score: intravertebral instability (≥ 5 mm), focal kyphosis (≥ 10°), duration of symptoms (≥ 30 days), intravertebral cleft, and previous history of vertebral fracture. Internal validation showed a mean optimism of 0.019 with a corrected AUC of 0.77. A cut-off of ≤ one point was chosen to classify a low risk of AVF, for which only four of 137 patients (3%) had AVF with 92.5% sensitivity and 45.6% specificity. A cut-off of ≥ four points was chosen to classify a high risk of AVF, for which 22 of 38 (58%) had AVF with 41.5% sensitivity and 94.5% specificity. Conclusion In this study, the AVA score was found to be a simple preoperative method for the identification of patients at low and high risk of postoperative acute AVF. This model could be applied to individual patients and could aid in the decision-making before vertebral augmentation. Cite this article: Bone Joint J 2022;104-B(1):97–102.

Various studies have revealed that psychological stress enhances pruritus.1,2 The COVID-19 pandemic have increased psychological stress. People may feel additional psychological stress in at-risk circumstances for the spread of COVID-19 infection. However, it is unknown whether at-risk circumstances for COVID-19, such as confirmed infection in acquaintances, are associated with the risk of pruritus. Thus, we investigated the association between at-risk circumstances and pruritus in the general population via cross-sectional and longitudinal analyses.

Understanding the origin of acid mine drainage (AMD) in a closed mine and groundwater flow system around the mine aids in developing strategies for environmental protection and management. AMD has been continuously collected and neutralized at Osarizawa Mine, Akita Prefecture, Japan, since the mine was closed in the 1970s, to protect surrounding river water and groundwater quality. Thus, water samples were taken at the mine and surrounding groundwaters and rivers to characterize the chemical properties and environmental isotopes (δ2H and δ18O). The results showed that the quality and stable isotope ratios of AMD differed from those of groundwater/river water, indicating that the recharge areas of AMD. The recharge area of AMD was evaluated as the mountain slope at an elevation of 400–500 m while that of the surrounding groundwater was evaluated at an elevation of 350–450 m, by considering the stable isotopes ratios. This indicates that the groundwater affected by AMD is limited to the vicinity of the mine and distributed around nearby rivers.

Background Previous studies have shown that diarrhea is associated with increased mortality of patients in intensive care units (ICUs). However, these studies used dichotomized cutoff values, even if diarrhea was a continuous condition. This study aimed to assess the association between diarrhea quantity and mortality in ICU patients with newly developed diarrhea. Methods We conducted this single-center retrospective cohort study at the Kameda Medical Center ICU. We consecutively included all adult ICU patients with newly developed diarrhea in the ICU between January 2017 and December 2018. Newly developed diarrhea was defined based on a Bristol stool chart scale ≥ 6 and frequency of diarrhea ≥ 3 times per day. We excluded patients who already had diarrhea on the day of ICU admission among other criteria. We collected data on the quantity of diarrhea on the day when patients newly developed diarrhea. The primary outcome was in-hospital mortality. The risk ratio (RR) and 95% confidence interval (CI) for the association between the quantity of diarrhea and mortality were estimated using multivariable-modified Poisson regression models adjusted for the Charlson Comorbidity Index, sequential organ failure assessment score, and serum albumin levels. Results Among 231 participants, 68.4% (158/231) were men; the median age of the patients was 72 years. The median quantity of diarrhea was 401 g (interquartile range [IQR] 230‒645 g), and in-hospital mortality was 22.9% (53/231). More diarrhea at baseline was associated with higher in-hospital mortality; the unadjusted RR (95% CI) per 200-g increase was 1.10 (1.01‒1.19). This association remained in the multivariable-adjusted analysis; the adjusted RR (95% CI) per 200-g increase was 1.10 (1.01‒1.20). Conclusions A greater quantity of diarrhea was an independent risk factor for in-hospital mortality. The quantity of diarrhea may be an indicator of disease severity in ICU patients.

Background To combat the coronavirus disease 2019 pandemic, many countries, including Japan, implemented policies limiting social activities and encouraging preventive behaviors. This study examines the influence of such policies on the trends of 10 infectious pediatric diseases: pharyngoconjunctival fever; group A streptococcal pharyngitis; infectious gastroenteritis; chickenpox; erythema infectiosum; hand, foot, and mouth disease; herpangina; respiratory syncytial virus; exanthem subitum; and mumps. Methods The research adopted a retrospective cohort study design. We collected data from Japan’s National Epidemiological Surveillance Program detailing the incidences of the 10 diseases per pediatric sentinel site for a period beginning at nine weeks before government‐ordered school closures and ending at nine weeks after the end of the state of emergency. We obtained corresponding data for the equivalent weeks in 2015–2019. We estimated the influence of the policies using a difference‐in‐differences regression model. Results For seven diseases (pharyngoconjunctival fever; group A streptococcal pharyngitis; infectious gastroenteritis; chickenpox; erythema infectiosum; hand, foot, and mouth disease; and herpangina), the incidence in 2020 decreased significantly during and after the school closures. Sensitivity analysis, in which the focus area was limited to the policy‐implementation period or existing trend patterns, replicated these significant decreases for one of the above mentioned seven diseases—infectious gastroenteritis. Conclusions Policies such as school closures and encouragement of preventive behaviors were associated with significant decreases in the incidences of most of the 10 diseases, which sensitivity analysis replicated in infectious gastroenteritis. To determine the long‐term effects of these policies, prospective cohort studies are needed.

BackgroundThis study aimed to develop criteria for identifying patients with acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) from Japanese administrative data and validate the pre-existing criteria.MethodsThis retrospective, multi-center validation study was conducted at eight institutes in Japan to verify the diagnostic accuracy of the disease name for AE-IPF. We used the Japanese Diagnosis Procedure Combination data to identify patients with a disease name that could meet the diagnostic criteria for AE-IPF, who were admitted to the eight institutes from January 2016 to February 2019. As a reference standard, two respiratory physicians performed a chart review to determine whether the patients had a disease that met the diagnostic criteria for AE-IPF. Furthermore, two radiologists interpreted the chest computed tomography findings of cases considered AE-IPF and confirmed the diagnosis. We calculated the positive predictive value (PPV) for each disease name and its combination.ResultsWe included 830 patients; among them, 216 were diagnosed with AE-IPF through the chart review. We combined the groups of disease names and yielded two criteria: the criteria with the highest PPV (0.72 [95% confidence interval 0.62 to 0.81]) and that with a slightly less PPV (0.61 [0.53 to 0.68]) but more true positives. Pre-existing criteria showed a PPV of 0.40 (0.31 to 0.49).ConclusionThe criteria derived in this study for identifying AE-IPF from Japanese administrative data show a fair PPV. Although these criteria should be carefully interpreted according to the target population, our findings could be utilized in future database studies on AE-IPF.

Background Although nursery school teachers may experience depressive symptoms, there have been few studies exploring the associated factors. The objective of this study was to determine the prevalence of depression and explore its associated factors in nursery school teachers. Methods This cross-sectional study surveyed nursery school teachers in Sakyo-ku, Kyoto City to determine the prevalence of depressive symptoms as measured by the five-item Mental Health Inventory. We used a logistic regression model to assess the factors. Results Respondents were 148 teachers (36%) out of 410 nursery school teachers in 21 nursery schools, and 65 (44%) indicated that they had depressive symptoms. Using the Work Limitation Questionnaire (WLQ), productivity loss score (adjusted risk ratio [ARR], 1.17; 95% confidence interval [95% CI], 1.02 to 1.34) and psychological demands (ARR, 1.25; 95% CI, 1.02 to 1.53) were found to be associated with depressive symptoms. Conclusions The associated factors with depressive symptoms were high psychological demands and a high degree of presenteeism. Further prospective cohort studies with larger sample sizes should be conducted to confirm these relationships.