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Chronic insomnia is common and associated with reduced quality of life. Benzodiazepine hypnotics are commonly prescribed for insomnia, but have potential side effects including concentration impairment, somnolence, and dependence. Lemborexant is an orexin receptor antagonist considered to have fewer side effects. The objectives of this study were to evaluate in detail the effects of lemborexant and examine whether the addition of lemborexant could gradually taper off benzodiazepine hypnotics. We retrospectively examined the effectiveness of lemborexant in 28 outpatients with insomnia. Insomnia symptoms were assessed using the Athens Insomnia Scale before and after lemborexant administration. We also attempted to taper and assessed doses of benzodiazepine hypnotics using diazepam equivalents for some patients taking benzodiazepine hypnotics. The mean Athens Insomnia Scale score was significantly improved after lemborexant treatment (8.7 ± 5.2 vs. 3.8 ± 3.3; p

Objective This study examined the pharmacokinetics, safety and anti-tumor activity of docetaxel at a dose of 100 mg/m2 in Japanese patients with advanced or recurrent breast cancer. Methods Japanese patients with advanced or recurrent breast cancer received docetaxel at a dose of 100 mg/m2 intravenously every three weeks. The pharmacokinetics were assessed during the first cycle. The patients were allowed to receive supportive care drugs based on the indications and dosages in Japan. Results Six eligible patients aged 39-65 years old and 27 treatment cycles were analyzed. All patients experienced one or more adverse events (AEs). The common AEs were neutropenia, thrombocytopenia, alopecia, rash, diarrhea, neuropathy (sensory), fatigue, nausea, fever, hypoalbuminemia, alanine transaminase (ALT) increased, constipation, and taste alteration. Grade 3 or 4 AEs included neutropenia, leukopenia, anemia, lymphopenia, decreased appetite, γ-glutamyl transpeptidase (GTP) increased, aspartate transaminase (AST) increased, ALT increased, hypertension and cellulitis which were all reversible. There were no cases of febrile neutropenia, serious AEs or deaths. The median number of cycles was six. Dose reductions were not observed and most cycles were administered at their intended doses. No complete response and three partial responses were observed in four assessable patients with evaluable lesions. The maximum concentration and area under the blood concentration-time curve were 3,417.5 ng/mL and 4.35 μg・hr/mL (mean), respectively. Conclusion Docetaxel at a dose of 100 mg/m2 was tolerable with acceptable safety profiles and effective for Japanese patients with advanced or recurrent breast cancer with appropriate supportive therapies, and pharmacokinetic (PK) profiles which corresponded approximately with the findings of previous clinical studies.

Background Patient-reported outcome (PRO) measures can provide valuable information in evaluating patients’ health-related quality of life (HRQoL). Post hoc analysis of the AFTERCAB study was conducted to evaluate the HRQoL benefit of enzalutamide plus androgen deprivation therapy (ADT) compared to flutamide plus ADT for the treatment of patients with castration-resistant prostate cancer (CRPC) in Japan. Methods The open-label AFTERCAB study was conducted from November 2016 to March 2020 in Japanese men aged ≥ 20 years with asymptomatic or mildly symptomatic CRPC. Patients received enzalutamide plus ADT or flutamide plus ADT, respectively, as first-line alternative androgen therapy (AAT). HRQoL was analyzed through the Functional Assessment of Cancer Therapy–Prostate, EuroQoL 5-Dimension 5-Level instruments, Brief Pain Inventory–Short Form, and Brief Fatigue Inventory. The longitudinal changes in HRQoL, HRQoL deterioration based on minimally important difference (MID), and time to HRQoL deterioration were evaluated for first-line AAT. Results Overall, HRQoL between the enzalutamide and flutamide groups was similar during first-line treatment. No statistically significant HRQoL difference in change from baseline to week 61 (least square mean difference; p value) was observed. Furthermore, proportions of pain progression, symptom worsening, and HRQoL deterioration based on MID, were not significantly different between groups. Conclusions The results were similar in all subscales of each PRO, demonstrating similar HRQoL deterioration based on MID criteria between the enzalutamide and flutamide groups.

The J‐CAPRA score is an assessment tool which stratifies risk and predicts outcome of primary androgen deprivation therapy (ADT) using prostate‐specific antigen, Gleason score, and clinical TNM staging. Here, we aimed to assess the generalisability of this tool in multi‐ethnic Asians. Performance of J‐CAPRA was evaluated in 782 Malaysian and 16,946 Japanese patients undergoing ADT from the Malaysian Study Group of Prostate Cancer (M‐CaP) and Japan Study Group of Prostate Cancer (J‐CaP) databases, respectively. Using the original J‐CAPRA, 69.6% metastatic (M1) cases without T and/or N staging were stratified as intermediate‐risk disease in the M‐CaP database. To address this, we first omitted clinical T and N stage variables, and calculated the score on a 0–8 scale in the modified J‐CAPRA scoring system for M1 patients. Notably, treatment decisions of M1 cases were not directly affected by both T and N staging. The J‐CAPRA score threshold was adjusted for intermediate (modified J‐CAPRA score 3–5) and high‐risk (modified J‐CAPRA score ≥6) groups in M1 patients. Using J‐CaP database, validation analysis showed that overall survival, prostate cancer‐specific survival, and progression‐free survival of modified intermediate and high‐risk groups were comparable to those of original J‐CAPRA (p > 0.05) with Cohen's coefficient of 0.65. Around 88% M1 cases from M‐CaP database were reclassified into high‐risk category. Modified J‐CAPRA scoring system is instrumental in risk assessment and treatment outcome prediction for M1 patients without T and/or N staging., The modified J‐CAPRA scoring system is a risk assessment tool to predict the outcome of primary androgen deprivation therapy (ADT) based on Gleason score, prostate‐specific antigen, and clinical M stage alone. It is beneficial and applicable in stratifying the risk and predicting the treatment outcomes of M1 patients without T and/or N staging.

Background To best employ radium‐223 dichloride (Ra‐223) for patients with castration‐resistant prostate cancer (CRPC) and bone metastasis, we investigated the bone‐predominant status in patients treated with Ra‐223. Methods We retrospectively evaluated 127 CRPC patients who underwent treatment with Ra‐223. The patients were divided into three groups based on the types of dynamic changes of bone metastasis between diagnosis and just before Ra‐223: (a) only known lesions; (b) de novo lesions; (c) new progressive lesions. We developed the risk assessment using predictive factors based on progression‐free survival (PFS). Results During the median follow‐up period of 10.4 months, the median PFS in the only known lesions group was 11.3 months compared to 8.1 months in the de novo lesions group and 5.1 months in the new progressive lesions group (P 1 (HR 1.74, 95% CI 1.04‐2.89, P = .034), PSA value of >100 ng/mL (HR 1.59, 95% CI 1.02‐2.50, P = .043), and PSA doubling time (PSADT) of, We developed the risk assessment based on the types of dynamic changes of bone metastasis before the use of radium‐223 dichloride (Ra‐223). This risk assessment can be used to maximize the clinical benefits of Ra‐223 treatment for bone‐predominant metastasis.

Background Although neoadjuvant chemotherapy provides survival benefits in muscle-invasive bladder cancer, the impact of neoadjuvant chemotherapy on health-related quality of life has not been investigated by a randomized trial. The purpose of this study is to compare health-related quality of life in patients with muscle-invasive bladder cancer who received neoadjuvant chemotherapy followed by radical cystectomy or radical cystectomy alone based on patient-reported outcome data. Methods Patients were randomized to receive two cycles of neoadjuvant methotrexate, doxorubicin, vinblastine, and cisplatin followed by radical cystectomy or radical cystectomy alone. Health-related quality of life was measured using the Functional Assessment of Cancer Therapy-Bladder (version 4) questionnaire before the protocol treatments, after neoadjuvant chemotherapy, after radical cystectomy and 1 year after registration. Results A total of 99 patients were analysed. No statistically significant differences in postoperative health-related quality of life were found between the arms. In the neoadjuvant chemotherapy arm, the scores after neoadjuvant chemotherapy were significantly lower than the baseline scores in physical well-being, functional well-being, Functional Assessment of Cancer Therapy-General total, weight loss, diarrhoea, appetite, body appearance, embarrassment by ostomy appliance and total Functional Assessment of Cancer Therapy-Bladder. However, there was no difference in scores for these domains, except for embarrassment by ostomy appliance, between the two arms after radical cystectomy and 1 year after registration. Conclusions Although health-related quality of life declined during neoadjuvant chemotherapy, no negative effect of neoadjuvant chemotherapy on health-related quality of life was apparent after radical cystectomy. These data support the view that neoadjuvant chemotherapy can be considered as a standard of care for patients with muscle-invasive bladder cancer regarding health-related quality of life.

Objectives Despite just a 4-year interval from the last version (2015) of the Clinical Practice Guidelines for Bladder Cancer, several dramatic paradigm shifts have occurred in the latest clinical practice regarding both the diagnosis and treatment of bladder cancer. Herein, we updated the 2019 version of the Clinical Practice Guidelines for Bladder Cancer under the instruction of the Japanese Urological Association. Methods We previously reported in a revision working position paper for Clinical Practice Guidelines for Bladder Cancer 2019 edition and described the methods of revision detail. Results The major points of change in the 2019 version are presented and explanations are given as follows: (i) introduction of the new reference assessment system; (ii) modification of the risk classification for non-muscle-invasive bladder cancer; (iii) addition of clinical questions for the new tumor-visible techniques in non-muscle-invasive bladder cancer; (iv) inclusion of minimally invasive surgeries for muscle-invasive bladder cancer and immune checkpoint inhibitors for locally advanced/metastatic muscle-invasive bladder cancer; (v) overview chapter of the histological variant of urothelial cancer and rare cancers of the bladder; and (vi) recommendation of follow up in non-muscle-invasive bladder cancer and muscle-invasive bladder cancer. Conclusions Guidelines should be updated based on the current evidence and updates carried out without delay. The hope is that this guidelines will be assessed by many urologists and will be the cornerstone for the next revision.

Background A previous comparative study in Japan has demonstrated that the two consecutive UroVysion tests are useful tools to detect the presence of bladder cancer during follow-up after transurethral resection, but they also presented their high rates of false-positive results. Here, we aimed to evaluate the relationship between the UroVysion tests and subsequent intravesical recurrence. Methods In the previous study, patients without bladder cancer during the first analysis showed the same examination set repeated 3 months later as the second analysis. In this follow-up study, 326 patients showed negative findings confirmed on cystoscopy during the second UroVysion test. Recurrence-free survival was assessed using a median follow-up of 27 months. Results In the two consecutive UroVysion tests, 214 patients (65.6%) showed negative UroVysion results in both tests, whereas 91 presented a positive result on either tests and 21 patients presented positive results in both tests. During the follow-up, 40 patients (12.3%) had an intravesical recurrence with non-muscle-invasive bladder cancer. The recurrence rates in patients with negative results in both tests, those with one positive result in either tests, and those with positive results in both tests were 8.4%, 16.5%, and 33.3%, respectively. The multivariate analysis indicated that the history of bladder cancer and the consecutive UroVysion test pattern were independent risk factors for recurrence. Conclusions Our data confirmed the effectiveness of two consecutive UroVysion tests in predicting intravesical recurrence after TURBT. Further prospective studies would help determine an appropriate interval for cystoscopy follow-up.

This study aimed to analyze the survival rate and to examine the risk of death from prostate cancer when accounting for competing risk of death, in men aged ≥80 y treated with primary androgen deprivation therapy (ADT). Data of patients with prostate cancer who had received ADT were extracted from a nationwide community‐based database established by the Japan Study Group for Prostate Cancer. Prognostic variables, including progression‐free survival, cancer‐specific survival, overall survival, and death rates were compared between men stratified by prostate cancer risk. Overall, 4760 patients older than 80 y were included. The proportion of low‐, intermediate‐, high‐, or very high‐risk, regional, and metastatic prostate cancer among super‐elderly men was 9.5%, 14.6%, 48.8%, 9.0%, 3.2%, and 24.9%, respectively. Survival rates decreased with increasing risk stratification. The cumulative 5‐y death rate by prostate cancer for low‐, intermediate‐, high‐, or very high‐risk, regional, and metastatic prostate cancer, was 0.92% (95% confidence interval [CI]: 0.2%‐3.6%), 1.6% (95% CI: 0.8%‐3.4%), 5.75% (95% CI: 4.25%‐7.75%), 15.6% (95% CI: 11.6%‐23.3%), 20.7% (95% CI: 13.1%‐31.7%), and 36.9% (95% CI: 32.8%‐41.4%), respectively. Our findings support that there is no need for immediate ADT for low‐ and intermediate‐risk groups. Conversely, in high‐ or very high‐risk, regional, and metastatic prostate cancer, more efforts for curative therapy and intensive therapy are needed in selected patients., This manuscript investigated the survival rate and examined the risk of death from prostate cancer when accounting for competing risk of death, in men aged ≥80 y to clarify which subset benefitted from androgen deprivation therapy (ADT). The cumulative 5‐y death rates by prostate cancer for low‐risk, and intermediate‐risk were very low, supporting no need for immediate ADT. In addition, the cumulative 5‐y death rate by prostate cancer for high‐risk or very high‐risk, regional, and metastatic prostate cancer was high, more effort for curative therapy and intensive therapy are needed in selected patients.

Background Oral anticoagulants use has increased rapidly, internationally. Here we look at risks and benefits, based on Japanese data, of therapy with low risk non-valvular atrial fibrillation patients. Objectives Using a health insurance claims data set we assessed: (i) oral anticoagulants usage in Japan, and (ii) efficacy and safety of dabigatran compared with warfarin, in Japanese patients with non-valvular atrial fibrillation, aged 18–74 years. Methods We identified 4380 non-valvular atrial fibrillation patients treated with anticoagulants between 1 January 2005, and 28 February 2014, and estimated the adjusted hazard ratio for stroke or systemic embolism, and any hemorrhagic event (Cox proportional hazards regression model with stabilized inverse probability treatment weighting). Results The data included 101 989 anticoagulant prescriptions for 4380 patients, of which direct oral anticoagulants increased to 40.0% of the total by the end of the study. After applying exclusion criteria, 1536 new non-valvular atrial fibrillation patients were identified, including 1071 treated with warfarin and 465 with dabigatran. Mean ages were 56.11 ± 9.70 years for warfarin, and 55.80 ± 9.65 years for dabigatran. The adjusted hazard ratio (95% confidence interval), comparing dabigatran with warfarin, was 0.48 (0.25–0.91) for stroke or systemic embolism, and 0.91 (0.60–1.39) for any hemorrhage including intracranial and gastrointestinal. Conclusions Number of patients prescribed direct oral anticoagulants steadily increased, and incidence of all-cause bleeding related to dabigatran was similar to warfarin, in our study population of younger non-valvular atrial fibrillation patients. Dabigatran, compared with warfarin, generally reduced risk of all-cause stroke and systemic embolism.

ObjectivesWe examined the efficacy of case management (CM) interventions to encourage participation in colorectal cancer screening for patients with schizophrenia. This study aimed to clarify patients’ acceptability of the intervention and the helpful components of the intervention. Simultaneously, the study aimed to determine the acceptability, appropriateness and feasibility of the intervention from the perspective of psychiatric care providers.Study design and settingThis study was a secondary qualitative analysis of a mixed-method randomised controlled trial that evaluated the efficacy of the CM approach to encourage participation in cancer screening for people with schizophrenia. The intervention comprised education and patient navigation for colorectal cancer screening. Interviews were conducted with patients who received the intervention and staff from two psychiatric hospitals in Japan who delivered the intervention.ParticipantsOf the 172 patients with schizophrenia who participated in the trial, 153 were included. In addition, three out of six providers were included.Data collection and analysisUsing a structured interview, the case manager asked participants about patient acceptability and the helpful components of the intervention. Content analysis was conducted for the responses obtained, and the number of responses was tabulated by two researchers. For the interviews with the providers, opinions obtained from verbatim transcripts were extracted and summarised.ResultsForty-three of the 56 patients perceived that the intervention was acceptable. For the intervention component, inperson counselling with an explanation of the screening process by psychiatric care providers was most frequently reported by the patients as helpful (48 of the 68 respondents). Psychiatric care providers evaluated the intervention as acceptable, appropriate and easy to understand and administer. However, providing the intervention to all patients simultaneously was considered difficult with the current human resources.ConclusionsThis study showed that the CM intervention was perceived as acceptable by patients and acceptable and appropriate by psychiatric care providers.Trial registration numberUMIN000036017.

Objectives The objective of the study is to compare the efficacy and safety of alternative androgen therapy (AAT) with enzalutamide + androgen deprivation therapy (ADT) and flutamide + ADT in the treatment of Japanese men with metastatic or nonmetastatic castration‐resistant prostate cancer (CRPC) who progressed despite combined androgen blockade (CAB) with bicalutamide + ADT. AAT treatment sequence was also investigated. Materials and methods The open‐label, Phase 4 AFTERCAB study (NCT02918968) was conducted from November 2016 to March 2020 in Japanese men aged ≥20 years with asymptomatic or mildly symptomatic CRPC. Patients were initially randomized to enzalutamide (160 mg/day) + ADT (enzalutamide first) or flutamide (375mg/day [125mg three times daily]) + ADT (flutamide first) as first‐line therapy. Following prostate‐specific antigen (PSA) progression, other disease progression, or discontinuation of first‐line therapy due to an adverse event (AE), patients switched to the other treatment as second‐line therapy. The primary endpoint was time to PSA progression with first‐line therapy (TTPP1). Secondary endpoints included TTPP2 (TTPP1 + time to PSA progression with second‐line therapy). AEs were monitored to assess safety. Results Overall, 206 men were randomized (enzalutamide first, n = 102; flutamide first, n = 104) and stratified by study site and disease stage; 133 patients transitioned to second‐line therapy (enzalutamide first, n = 48; flutamide first, n = 85). TTPP1 was significantly improved with enzalutamide first versus flutamide first (median 21.4 months vs. 5.8 months; hazard ratio [HR] 0.42; 95% confidence interval [CI] [0.29, 0.61]). TTPP2 was numerically improved with enzalutamide first versus flutamide first (median not reached vs. 21.2 months; HR 0.76; 95% CI [0.48, 1.19]). Both treatments were generally well tolerated, with AEs consistent with their known safety profiles. Conclusion First‐line AAT with enzalutamide + ADT provided a significant improvement in time to PSA progression versus flutamide + ADT. Enzalutamide + ADT may therefore be the preferred first‐line AAT option in Japanese men with metastatic or nonmetastatic CRPC who progress despite CAB with bicalutamide + ADT.

First‑line chemotherapy for men with metastatic castration‑resistant prostate cancer (mCRPC) has been employed to improve overall survival (OS) and progression‑free survival (PFS). However, several new agents for CRPC after first‑line chemotherapy prolonged survival by only a few months. To develop a new treatment modality, we conducted a phase III randomized trial of personalized peptide vaccination (PPV) for human leukocyte antigen (HLA)‑A24‑positive patients with castration‑resistant prostate cancer (CRPC) for whom docetaxel chemotherapy failed. This randomized, double‑blind, placebo‑controlled, phase III trial was carried out at 68 medical centers in Japan. Patients were randomly assigned at a 2:1 ratio to receive PPV or placebo. Four of 12 warehouse peptides selected based on pre‑existing peptide‑specific immunoglobulin G levels or the corresponding placebo were subcutaneously injected in 6 doses weekly and then bi‑weekly following the maximum of 30 doses until disease progression. The primary end‑point was overall survival (OS). Efficacy analyses were performed by the full analysis set. Between August 2013 and April 2016, 310 patients were randomly assigned, and 306 patients were analyzed. Baseline characteristics were balanced between groups. The estimated median OS was 16.1 months [95% confidence interval (CI), 13‑18.2] with PPV and 16.9 months (95% CI, 13.1‑20.4) with placebo [hazard ratio (HR), 1.04, 95% CI, 0.80‑1.37; P=0.77]. Grade ≥3 adverse events were observed in 41% of both groups. The analysis of treatment arm effects among subgroups revealed lower HRs for OS in favor of the PPV arm in patients with

Background To develop a new treatment modality, we conducted a phase 3 randomized trial of personalized peptide vaccination (PPV) for human leukocyte antigen (HLA)-A24-positive patients with castration-resistant prostate cancer (CRPC) for whom docetaxel chemotherapy failed. Methods This randomized, double-blind, placebo-controlled, phase 3 trial was done at 68 medical centers in Japan. Eligible patients were aged 20 years or older, positive immunoglobulin G (IgG) responses to at least 2 of 12 warehouse peptides, an Eastern Cooperative Oncology Group performance status of 0 or 1, life expectancy of at least 12 weeks, serum testosterone level of ≤ 50 ng/dl, and satisfactory bone marrow function, hepatic function, and renal function. Patients were randomly assigned in a 2:1 ratio to receive PPV or placebo. Four of 12 warehouse peptides selected based on pre-existing peptide-specific IgG levels or the corresponding placebo were subcutaneously injected in 6 doses weekly and then bi-weekly following the maximum of 30 doses until disease progression. The primary end point was overall survival (OS). Efficacy analyses were by the full analysis set. Results Between August 2013 and April 2016, 310 patients were randomly assigned, and 306 patients were analyzed. Baseline characteristics were balanced between groups. The estimated median OS was 16.1 months (95% confidence interval [CI], 13–18.2) with PPV and 16.9 months (95% CI, 13.1–20.4) with placebo (hazard ratio [HR], 1.04, 95% CI, 0.80–1.37; p = 0.77). Grade ≥ 3 adverse events were observed in 41% in both groups. The analysis of treatment arm effects among subgroups revealed lower HRs for OS in favor of the PPV arm in patients with < 64% neutrophils (HR, 0.55, 95% CI, 0.33–0.93; p = 0.03) or ≥ 26% lymphocytes (HR, 0.70, 95% CI, 0.52–0.92; p = 0.02) at base line. Conclusions PPV did not prolong OS in HLA-A24-positive patients with CRPC progressing after docetaxel chemotherapy. Subgroup analysis suggested that the patients with a lower proportion of neutrophils or a higher proportion of lymphocytes at base line can receive survival benefits from PPV treatment.

Background In this age of antimicrobial resistance, unnecessary use of antibiotics to treat non-bacterial acute respiratory tract infections (ARTIs) and inappropriate use of antibiotics in treating bacterial ARTIs are public health concerns. Purpose Our aim is to identify the pattern of oral antibiotic prescriptions for outpatients with ARTIs in Japan. Methods We analysed health insurance claims data of patients (aged ≤74 years) from 2013 to 2015, to determine the pattern of antibiotic prescriptions for outpatient ARTIs and calculated the proportion of each antibiotic. Results Data on 4.6 million antibiotic prescriptions among 1559394 outpatients with ARTIs were analysed. The most commonly prescribed classes of antibiotics included cephalosporins (41.9%), macrolides (32.8%) and fluoroquinolones (14.7%). The proportion of first-, second- and third-generation cephalosporins was 1.0%, 1.7% and 97.3%, respectively. Fluoroquinolones accounted for a quarter of the prescriptions for ARTIs in patients aged >20 years. In contrast, penicillins accounted for just 8.0% of the total number of antibiotic prescriptions for ARTIs. Conclusions According to clinical guidelines, penicillins are first-line antibiotics against ARTIs. However, third-generation cephalosporins, macrolides and fluoroquinolones are more frequently prescribed in Japan. Although we could not assess the extent to which appropriate antibiotics are selected, our results support the necessity of improving antibiotic choices in the treatment of ARTIs.

Dementia is a major public health concern in ageing societies. Although the population of Japan is among the most aged worldwide, long-term trends in the place of death (PoD) among patients with dementia is unknown. In this Japanese nationwide observational study, we analysed trends in PoD using the data of patients with dementia who were aged ≥65 years and died during 1999–2016. Trends in the crude death rates and PoD frequencies were analysed using the Joinpoint regression model. Changes in these trends were assessed using the Joinpoint regression analysis in which significant change points, the annual percentage change (APC) and average APCs (AAPC) in hospitals, homes, or nursing homes were estimated. During 1999–2016, the number of deaths among patients with dementia increased from 3,235 to 23,757 (total: 182,000). A trend analysis revealed increased mortality rates, with an AAPC of 8.2% among men and 9.3% among women. Most patients with dementia died in the hospital, although the prevalence of hospital deaths decreased (AAPC: -1.0%). Moreover, the prevalence of nursing home deaths increased (AAPC: 5.6%), whereas the prevalence of home deaths decreased (AAPC: -5.8%). These findings support a reconsideration of the end-of-life care provided to patients with dementia.

ObjectivesFall-related mortality among older adults is a major public health issue, especially for ageing societies. This study aimed to investigate current trends in fall-related mortality in Japan using nationwide population-based data covering 1997–2016.DesignWe analysed fall-related deaths among older persons aged ≥65 years using the data provided by the Japanese Ministry of Health, Labour and Welfare.ResultsThe crude and age-standardised mortality rates were calculated per 100 000 persons by stratifying by age (65–74, 75–84 and ≥85 years) and sex. To identify trend changes, a joinpoint regression model was applied by estimating change points and annual percentage change (APC). The total number of fall-related deaths in Japan increased from 5872 in 1997 to 8030 in 2016, of which 78.8% involved persons aged ≥65 years. The younger population (65–74 years) showed continuous and faster-decreasing trends for both men and women. Average APC among men aged ≥75 years did not decrease. Among middle-aged and older women (75–84 and ≥85 years) decreasing trends were observed. Furthermore, the age-adjusted mortality rate of men was approximately twice that of women, and it showed a faster decrease for women.ConclusionsAlthough Japanese healthcare has shown improvement in preventing fall-related deaths over the last two decades, the crude mortality for those aged over 85 years remains high, indicating difficulty in reducing fall-related deaths in the super-aged population. Further investigations to uncover causal factors for falls in older populations are required.

Background This study investigated how differences in the method of the first‐line androgen deprivation therapy (ADT) affected the time to castration‐resistant prostate cancer. Methods The Japan Study Group of Prostate Cancer compiled a nationwide community‐based database on prostate cancer patients who underwent ADT. That database included 13 774 patients who were started on ADT by surgical or medical castration alone (monotherapy group, 5395 cases) or ADT in combination with a nonsteroidal anti‐androgen (combined androgen blockade (CAB) group, 8379 cases). We used logistic regression analysis with background factors as independent factors to calculate propensity scores in regard to selection of CAB. Next, for 8826 cases of propensity score‐matched patients, we compared the survival rates in the two groups. Results The CAB group showed a significantly better progression‐free survival (PFS) rate (65.6% vs 59.6% at 5 years; median time to progression, 11.6 vs 7.1 years; hazard ratio in the CAB group: 0.78, with a 95% confidence interval of 0.72 to 0.84; P

IntroductionOne of the reasons for the high mortality rate from cancer in people with schizophrenia is delay in diagnosis. Many studies have shown lower cancer screening rates in people with schizophrenia; however, there are no interventions for people with schizophrenia to increase cancer screening. Therefore, we developed a case management (CM) intervention to encourage participation in cancer screening. The purpose of this study was to examine the efficacy of CM to encourage participation in cancer screening for people with schizophrenia, with particular focus on colorectal cancer screening by faecal occult blood testing, compared with usual intervention (UI), namely, municipal public education.Methods and analysisThis is an individually randomised, parallel group trial with blinded outcome assessments. The participants will be randomly allocated to either the CM plus UI group or UI alone group in a 1:1 ratio using a web-based program at a data management centre. The primary end point of the study is participation in colorectal cancer screening in the year of intervention, which will be assessed based on municipal records.Ethics and disseminationThis study is performed in accordance with Ethical Guidelines for Medical and Health Research Involving Human Subjects published by Japan’s Ministry of Education, Science, and Technology and the Ministry of Health, Labour, and Welfare and the modified Act on the Protection of Personal Information as well as the Declaration of Helsinki. This study was approved by the institutional ethics committee at the Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital on 23 April 2019 (approval number: RIN1904-003). The findings of this trial will be submitted to an international peer-reviewed journal.Trial registration numberUMIN000036017.

Many biomarkers for sepsis are used in clinical practice; however, few have become the standard. We measured plasma histidine-rich glycoprotein levels in patients with systemic inflammatory response syndrome. We compared histidine-rich glycoprotein, procalcitonin, and presepsin levels to assess their significance as biomarkers.Single-center, prospective, observational cohort study.ICU at an university-affiliated hospital.Seventy-nine ICU patients (70 with systemic inflammatory response syndrome and 9 without systemic inflammatory response syndrome) and 16 healthy volunteers.None.We collected blood samples from patients within 24 hours of ICU admission. Histidine-rich glycoprotein levels were determined using enzyme-linked immunosorbent assay. The median histidine-rich glycoprotein level in healthy volunteers (n = 16) was 63.00 µg/mL (interquartile range, 51.53-66.21 µg/mL). Histidine-rich glycoprotein levels in systemic inflammatory response syndrome patients (n = 70; 28.72 µg/mL [15.74-41.46 µg/mL]) were lower than those in nonsystemic inflammatory response syndrome patients (n = 9; 38.64 µg/mL [30.26-51.81 µg/mL]; p = 0.049). Of 70 patients with systemic inflammatory response syndrome, 20 had sepsis. Histidine-rich glycoprotein levels were lower in septic patients than in noninfective systemic inflammatory response syndrome patients (8.71 µg/mL [6.72-15.74 µg/mL] vs 33.27 µg/mL [26.57-44.99 µg/mL]; p0.001) and were lower in nonsurvivors (n = 8) than in survivors (n = 62) of systemic inflammatory response syndrome (9.06 µg/mL [4.49-15.70 µg/mL] vs 31.78 µg/mL [18.57-42.11 µg/mL]; p0.001). Histidine-rich glycoprotein showed a high sensitivity and specificity for diagnosing sepsis. Receiver operating characteristic curve analysis for detecting sepsis within systemic inflammatory response syndrome patients showed that the area under the curve for histidine-rich glycoprotein, procalcitonin, and presepsin was 0.97, 0.82, and 0.77, respectively. In addition, survival analysis in systemic inflammatory response syndrome patients revealed that the Harrell C-index for histidine-rich glycoprotein, procalcitonin, and presepsin was 0.85, 0.65, and 0.87, respectively.Histidine-rich glycoprotein levels were low in patients with sepsis and were significantly related to mortality in systemic inflammatory response syndrome population. Furthermore, as a biomarker, histidine-rich glycoprotein may be superior to procalcitonin and presepsin.

Background: This prospective observational study elucidated the usefulness of hormonal therapy for localized prostate cancer. Background factors and the health-related quality of life in patients who initially underwent radical prostatectomy (RP) or primary androgen deprivation therapy (PADT) for localized prostate cancer are summarized. Materials and methods: Patients aged 67–76 years with clinical stage T1c or T2 localized prostate cancer treated with PADT or RP, a prostate-specific antigen concentration of

Trastuzumab emtansine (T-DM1), an anti-erb-b2 receptor tyrosine kinase 2 (HER2) antibody-drug conjugate, has been shown to significantly improve survival in HER2-positive breast cancer. We report a phase II trial of T-DM1 monotherapy in relapsed NSCLC with documented HER2 positivity (an immunohistochemistry [IHC] score of 3+, both an IHC score of 2+ and fluorescence in situ hybridization positivity, or exon 20 mutation). This study was terminated early because of limited efficacy. The demographic characteristics in the 15 assessable patients were as follows: median age, 67 years; male sex, 47%; performance status of 0 to 1, 80%; HER2 status IHC 3+, 33%; HER status IHC 2+/fluorescence in situ hybridization-positive, 20%; and exon 20 mutation, 47%. The median number of delivered cycles was 3 (range 1-11). One patient achieved a partial response with an objective response rate of 6.7% (90% confidence interval: 0.2-32.0). With a median follow-up time of 9.2 months, the median progression-free survival time and median survival time were 2.0 and 10.9 months, respectively. Grade 3 or 4 adverse events included thrombocytopenia (40%) and hepatotoxicity (20%) without any treatment-related deaths. T-DM1 had a limited efficacy for HER2-positive NSCLC in our cohort. Applying the concept of precision medicine to tumors appears challenging; thus, additional molecular approaches are warranted.

Background: Pharmacologic prophylaxis such as enoxaparin for venous thromboembolism (VTE) is rarely used in Japan, even following abdominal cancer surgery, for which it is recommended in relevant guidelines (at least 7 days of use) along with mechanical prophylaxis with intermittent pneumatic compression. Reasons for enoxaparin’s unpopularity include concerns over postoperative bleeding and its inconvenience in clinical practice. Here, we conducted a prospective clinical study of short-term (3 days) use of enoxaparin, which is considered to minimally impact postoperative management without increasing bleeding risk. Methods: Gastric cancer patients who underwent gastrectomy received enoxaparin for 3 days from postoperative day (POD) 1 to 4. The primary endpoint was the incidence of deep vein thrombosis (DVT), which was examined primarily via Doppler ultrasonography of the lower limbs between POD 8 and 14. The planned sample size was 70, which was calculated based on an estimated incidence rate of 9% and an upper limit of incidence rate of 20%, with alpha of 0.05 and beta of 0.2. Results: A total of 70 gastric cancer patients were enrolled, and ultimately, 68 patients received the protocol intervention and DVT evaluation. Sixty-seven patients completed 6 enoxaparin injections, but 1 patient did not complete the course due to abdominal bleeding after initiation. The incidence of DVT was 4.4% (3/68), and the 95% upper confidence interval was 12.2%, lower than the 20% threshold we set as the upper limit of DVT incidence. DVT was detected only in the peripheral veins of the lower extremities in all 3 affected patients. The incidence of bleeding-related complications, which were not severe, was 1.5% (1/68). Conclusions: Short-term (3 days) use of enoxaparin was shown to be effective and safe for VTE prophylaxis, comparable to regular use (at least 7 days), in postoperative management of gastric cancer surgery.

The progression-free survival in Japanese was similar to that recorded in the RECORD-1 study, whereas prolongation of overall survival was observed in this study compared with the RECORD-1 study., Objective Many studies have shown the efficacy of everolimus after pretreatment with vascular endothelial growth factor receptor-tyrosine kinase inhibitors. We investigated the efficacy and safety of everolimus as a second-line treatment after the failure of vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy in Japanese patients with advanced renal cell carcinoma. Methods This was an open-label, multicenter, phase II trial conducted in Japan through the central registration system. A total of 57 patients were enrolled. Patients were administered 10 mg of everolimus q.d. orally. The primary efficacy endpoint was progression-free survival achieved by administration of everolimus. Results The median progression-free survival of patients administered everolimus was 5.03 months (95% confidence interval: 3.70–6.20). The median overall survival was not reached. The objective response rate was 9.4% (95% confidence interval: 3.1–20.7). The progression-free survival in the group of

The Asian Prostate Cancer (A-CaP) Study is an Asia-wide initiative that has been developed over the course of 2 years. The study was launched in December 2015 in Tokyo, Japan, and the participating countries and regions engaged in preparations for the study during the course of 2016, including patient registration and creation of databases for the purpose of the study. The Second A-CaP Meeting was held on September 8, 2016 in Seoul, Korea, with the participation of members and collaborators from 12 countries and regions. Under the study, each participating country or region will begin registration of newly diagnosed prostate cancer patients and conduct prognostic investigations. From the data gathered, common research themes will be identified, such as comparisons among Asian countries of background factors in newly diagnosed prostate cancer patients. This is the first Asia-wide study of prostate cancer and has developed from single country research efforts in this field, including in Japan and Korea. At the Second Meeting, participating countries and regions discussed the status of preparations and discussed various issues that are being faced. These issues include technical challenges in creating databases, promoting participation in each country or region, clarifying issues relating to data input, addressing institutional issues such as institutional review board requirements, and the need for dedicated data managers. The meeting was positioned as an opportunity to share information and address outstanding issues prior to the initiation of the study. In addition to A-CaP-specific discussions, a series of special lectures was also delivered as a means of providing international perspectives on the latest developments in prostate cancer and the use of databases and registration studies around the world. (C) 2017 Asian Pacific Prostate Society, Published by Elsevier Korea LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

The Clinical Practice Guidelines for Bladder Cancer edited by the Japanese Urological Association were first published in 2009 and a revised edition was released in 2015. Four years has passed since the 2015 edition, and the clinical practice environment surrounding bladder cancer has drastically changed during that time. The main changes include: (i) insurance coverage of a new diagnostic method for non-muscle-invasive bladder cancer; (ii) insurance coverage of an immune checkpoint inhibitor in advanced and metastatic bladder cancer; and (iii) advances in robot-assisted radical cystectomy as a minimally invasive treatment for muscle-invasive bladder cancer. A paradigm shift in bladder cancer diagnosis and treatment is occurring day by day. Therefore, in this 2019 edition, while dealing with the above changes, we carefully selected clinical questions with clear evidence and included other clinically important points in the general statement. We also added a new chapter on rare cancers of the urinary tract. As a new method for the evaluation of study evidence level, we introduce "The Grading of Recommendations Assessment, Development and Evaluation" system modified to Japanese by the Medical Information Network Distribution Service.

The survival rate of cardiac arrest patients is less than 10%; therefore, development of a therapeutic strategy that improves their prognosis is necessary. Herein, we searched data collected from medical facilities throughout Japan for drugs that improve the survival rate of cardiac arrest patients. Candidate drugs, which could improve the prognosis of cardiac arrest patients, were extracted using “TargetMine,” a drug discovery tool. We investigated whether the candidate drugs were among the drugs administered within 1 month after cardiac arrest in data of cardiac arrest cases obtained from the Japan Medical Data Center. Logistic regression analysis was performed, with the explanatory variables being the presence or absence of the administration of those candidate drugs that were administered to ≥10 patients and the objective variable being the “survival discharge.” Adjusted odds ratios for survival discharge were calculated using propensity scores for drugs that significantly improved the proportion of survival discharge; the influence of covariates, such as patient background, medical history, and treatment factors, was excluded by the inverse probability-of-treatment weighted method. Using the search strategy, we extracted 165 drugs with vasodilator activity as candidate drugs. Drugs not approved in Japan, oral medicines, and external medicines were excluded. Then, we investigated whether the candidate drugs were administered to the 2,227 cardiac arrest patients included in this study. The results of the logistic regression analysis showed that three (isosorbide dinitrate, nitroglycerin, and nicardipine) of seven drugs that were administered to ≥10 patients showed significant association with improvement in the proportion of survival discharge. Further analyses using propensity scores revealed that the adjusted odds ratios for survival discharge for patients administered isosorbide dinitrate, nitroglycerin, and nicardipine were 3.35, 5.44, and 4.58, respectively. Thus, it can be suggested that isosorbide dinitrate, nitroglycerin, and nicardipine could be novel therapeutic agents for improving the prognosis of cardiac arrest patients.

The Asian Prostate Cancer (A-CaP) study is an Asia-wide initiative that was launched in December 2015 in Tokyo, Japan, with the objective of surveying information about patients who have received a histopathological diagnosis of prostate cancer (PCa) and are undergoing treatment and clarifying distribution of staging, the actual status of treatment choices, and treatment outcomes. The study aims to clarify the clinical situation for PCa in Asia and use the outcomes for the purposes of international comparison. Following the first meeting in Tokyo in December 2015, the second A-CaP meeting was held in Seoul, Korea, in September 2016. This, the third A-CaP meeting, was held on October 14, 2017, in Chiang Mai, Thailand, with the participation of members and collaborators from 12 countries and regions. In the meeting, participating countries and regions presented the current status of data collection, and the A-CaP office presented a preliminary analysis of the registered cases received from each country and region. Participants discussed ongoing challenges relating to data input and collection, institutional, and legislative issues that may present barriers to data sharing, and the outlook for further patient registrations through to the end of the registration period in December 2018. In addition to A-CaP–specific discussions, a series of special lectures were also delivered on the situation for health insurance in the United States, the correlation between insurance coverage and PCa outcomes, and the outlook for robotic surgery in the Asia-Pacific region. Members also confirmed the principles of authorship in collaborative studies, with a view to publishing original articles based on A-CaP data in the future. Keywords: Asia, Cancer, Database, Prospective study, Prostate cancer, Registry

Japan is still a medium-burden tuberculosis (TB) country. We aimed to examine trends in newly notified active TB incidence and TB-related mortality in the last two decades in Japan. This is a population-based study using Japanese Vital Statistics and Japan Tuberculosis Surveillance from 1997 to 2016. We determined active TB incidence and mortality rates (per 100 000 population) by sex, age and disease categories. Joinpoint regression was applied to calculate the annual percentage change (APC) in age-adjusted mortality rates and to identify the years showing significant trend changes. Crude and age-adjusted incidence rates reduced from 33.9 to 13.9 and 37.3 to 11.3 per 100 000 population, respectively. Also, crude and age-adjusted mortality rates reduced from 2.2 to 1.5 and 2.8 to 1.0 per 100 000 population, respectively. Average APC in the incidence and mortality rates showed significant decline both in men (−6.2% and −5.4%, respectively) and women (−5.7% and −4.6%, respectively). Age-specific analysis demonstrated decreases in incidence and mortality rates for every age category, except for the incidence trend in the younger population. Although trends in active TB incidence and mortality rates in Japan have favourably decreased, the rate of decline is far from achieving TB elimination by 2035.

The Asian Prostate Cancer (A-CaP) Study is an Asia-wide initiative that has been developed over the course of 2 years. The A-CaP Study is scheduled to begin in 2016, when each participating country or region will begin registration of newly diagnosed prostate cancer patients and conduct prognosis investigations. From the data gathered, common research themes will be identified, such as comparisons among Asian countries of background factors in newly diagnosed prostate cancer patients. This is the first Asia-wide study of prostate cancer and has developed from single country research efforts in this field, including in Japan and Korea. The inaugural Board Meeting of A-CaP was held on December 11, 2015 at the Research Center for Advanced Science and Technology, The University of Tokyo, attended by representatives of all participating countries and regions, who signed a memorandum of understanding concerning registration for A-CaP. Following the Board Meeting an A-CaP Launch Symposium was held. The symposium was attended by representatives of countries and regions participating in A-CaP, who gave presentations. Presentations and a keynote address were also delivered by representatives of the University of California San Francisco, USA, and the Peter MacCallum Cancer Centre, Australia, who provided insight and experience on similar databases compiled in their respective countries.

Infection is a common cause for an outpatient visit for young children. Pivalate-conjugated antibiotics (PCAs) are often used for these patients in Japan. However, a few case reports have shown that PCAs can provoke hypoglycemia in children, but no larger study has shown that PCAs increase the risk of hypoglycemia. The current study was performed as a retrospective review of children aged 1 month to 5 years old with at least once prescription of PCAs or other beta-lactam antibiotics from January 2011 to December 2013, using a medical and pharmacy claims database. Hypoglycemia was defined based on the International Statistical Classification of Diseases and Related Health Problems 10th Revision code or prescription of 10% or 20% glucose injection, and the incidence of hypoglycemic events was investigated. Logistic regression analysis was performed to examine the risk of hypoglycemia with PCAs compared with control antibiotics. The study cohort contained 179,594 eligible patients (male: 52.2%, mean age: 3.2 years). The numbers of prescriptions were 454,153 and 417,287 for PCAs and control antibiotics, respectively. Multivariate analysis showed that PCAs were associated with hypoglycemia (adjusted OR 1.18, 95% CI 1.12 to 1.24, P < 0.01), and the risk of hypoglycemia was also significantly increased with use of PCAs for ≤7 days (adjusted OR 1.17, 95% CI 1.11 to 1.24, P < 0.01). These results suggest that prescription of PCAs to young children should be avoided, even for a short time period.