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Under current bioequivalence guidelines in Japan, it is mandatory to establish bioequivalence using a single pivotal study. Clinical trials with limited resources usually have a pre-defined maximum permissible number of participants. In this manuscript, we considered a trial design that would allow for bioequivalence evaluation at an interim analysis in which the total number of participants takes into account the resource constraints. Then, available options at the interim analysis are group sequential designs and adaptive designs, A comparison of the performance of the two methods under same maximum participant number has not been conducted thus far. So we examined which method should be used by conducting a simulation study. Since bioequivalence is expected to be achieved at the interim analysis, a study design using a Pocock-type alpha spending function is preferrable. Simulation results using a Pocock-type alpha spending function showed similar performance between group sequential and adaptive designs. Consequently, due to statistical and operational complexity, it is preferable to choose group sequential designs for bioequivalence study in Japan. [ABSTRACT FROM AUTHOR]

Introduction: Intrahepatic cholangiocarcinoma (ICC) can be treated with chemotherapy in unresectable cases, but outcomes are poor. Proton beam therapy (PBT) may provide an alternative treatment and has good dose concentration that may improve local control. Methods: Fifty-nine patients who received initial PBT for ICC from May 2016 to June 2018 at nine centers were included in the study. The treatment protocol was based on the policy of the Japanese Society for Radiation Oncology. Forty patients received 72.6–76 Gy (RBE) in 20–22 fr, 13 received 74.0–76.0 Gy (RBE) in 37–38 fr, and 6 received 60–70.2 Gy (RBE) in 20–30 fr. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier analysis. Results: The 59 patients (35 men, 24 women; median age: 71 years; range: 41–91 years) had PS of 0 (n = 47), 1 (n = 10), and 2 (n = 2). Nine patients had hepatitis and all 59 cases were considered inoperable. The Child-Pugh class was A (n = 46), B (n = 7), and unknown (n = 6); the median maximum tumor diameter was 5.0 cm (range 2.0–15.2 cm); and the clinical stage was I (n = 12), II (n = 19), III (n = 10), and IV (n = 18). At the last follow-up, 17 patients were alive (median follow-up: 36.7 months; range: 24.1–49.9 months) and 42 had died. The median OS was 21.7 months (95% CI: 14.8–34.4 months). At the last follow-up, 37 cases had recurrence, including 10 with local recurrence. The median PFS was 7.5 months (95% CI: 6.1–11.3 months). In multivariable analyses, Child-Pugh class was significantly associated with OS and PFS, and Child-Pugh class and hepatitis were significantly associated with local recurrence. Four patients (6.8%) had late adverse events of grade 3 or higher. Conclusion: PBT gives favorable treatment outcomes for unresectable ICC without distant metastasis and may be particularly effective in cases with large tumors. [ABSTRACT FROM AUTHOR]

Aim: This study examined the relationship between continuity of social participation and progression of frailty among community‐dwelling older adults, by baseline frailty level. Methods: This study was part of a 3‐year community‐based cohort study among adults aged ≥65 years, living independently in a rural municipality in Japan. Mail surveys were carried out in 2016, 2018 and 2019. This study involved 2799 participants who responded to the question about social participation in every survey. Frailty was evaluated by Kihon Checklist total scores. Social participation was categorized into consistent non‐participation, interrupted recent non‐participation, interrupted recent participation and consistent participation. We assessed the relationship between social participation and change in frailty scores using general linear regression analysis, stratifying the participants into groups by their frailty level at baseline. Results: There was a smaller frailty score increase in the robust (β −0.61, 95% CI −0.99 to −0.22) and prefrail groups (β −0.73, 95% CI −1.18 to −0.27) for consistent participation than consistent non‐participation. Interrupted recent participation showed significant suppression in the prefrail group (β −0.96, 95% CI −1.60 to −0.32). Social participation had no clear effect on progression in the frail group. Conclusions: Consistent social participation might reduce the progression of frailty in robust and prefrail people. Inconsistent participation might also help to reduce progression in prefrail older adults. It is important for prefrail older adults to return to their social activities and continue to engage as long as possible, even if their participation was intermittent in the past. Geriatr Gerontol Int 2023; 23: 25–31. [ABSTRACT FROM AUTHOR]

Aim: Radio‐Taiso, a traditional exercise program in Japan, may serve as a coping strategy for older adults with frailty during the COVID‐19 pandemic. This phase II trial tested program adherence and safety and explored the potential effectiveness of a home‐based Radio‐Taiso. Methods: This assessor‐blind parallel randomized controlled trial included community‐dwelling Jolder Japanese adults with frailty and pre‐frailty. Fifty‐eight eligible participants were randomly allocated to intervention and control groups. Intervention participants performed 3–5‐min sessions of Radio‐Taiso one to four times per day for 12 weeks. Feasibility criteria were set at practice and retention rates of ≥75%. Safety was monitored by assessing all adverse events reported by participants during the intervention period, irrespective of causality. Potential effectiveness was exploratorily assessed using items that allow clinical interpretation of changes: mobility and health‐related quality of life (HR‐QoL), assessed using the modified short physical performance battery (SPPB) and the SF‐36, respectively. Results: Both practice (83%) and retention rates (100%) met the predetermined feasibility criteria. Eleven adverse events were reported but were supposedly unrelated to the intervention. In the intention‐to‐treat analysis, there was no clinically significant difference in the change in SPPB score between groups (−0.4 points, 95% confidence interval [CI], −1.2, 0.3); however, the intervention group scored higher in the mental component of HR‐QoL than did the control group (3.4 points, 95% CI: −1.1, 7.8). Conclusions: The preliminary data indicate that a phase III trial is feasible, focusing on the mental aspect of HR‐QoL as the primary outcome. Geriatr Gerontol Int 2023; 23: 32–37. [ABSTRACT FROM AUTHOR]

Purpose: In Japan, the incarceration of patients with eating disorders (EDs) owing to repeated shoplifting has become a social issue. This study examined the shoplifting behavior of inmates with EDs at our medical correctional center, with the objective of delineating their characteristics, identifying an adequate treatment plan, and preventing recidivism. Methods: The participants consisted of 32 incarcerated patients with EDs (22 females, 10 males) charged with shoplifting, from a medical correctional center in East Japan. A cross-sectional study was employed. Data were collected by retrieving the patients' medical records and through individual interviews conducted by psychiatrists. Results: The food-specific shoplifting ED group (those who had never shoplifted anything other than food) had a core pathology of the binge-purge type of anorexia nervosa with juvenile onset (p = 0.044). Furthermore, they demonstrated an average gap of 8 years between the onset of ED and their first shoplifting episode. The non-specific shoplifting ED group (those who shoplifted food and other items) typically shoplifted before the onset of ED (p = 0.001). They experienced the onset of ED after incarceration (p = 0.004) and had comorbid disorders (p = 0.024). The food-specific group required a psychosocial approach focusing on maintaining healthy body weight and mental stability, whereas the non-specific group required multiple forms of support for substance abuse and behavioral addiction, as well as interventions to reduce impulsive behavior. Conclusion: Early intervention is necessary to improve the prognosis of patients with EDs and shoplifting behavior. [ABSTRACT FROM AUTHOR]

Lewy body‐related α‐synucleinopathy (Lewy pathology) has been reported in patients with myotonic dystrophy (DM) type 1 (DM1), but no detailed report has described the prevalence and extent of its occurrence. We studied consecutive full autopsy cases of DM1 at the National Center of Neurology and Psychiatry (NCNP) Brain Bank for intractable psychiatric and neurological disorders. Thirty‐two cases, genetically determined to be DM1 (59.0 ± 8.7 years), obtained from the NCNP Brain Bank, were compared with control cases obtained from the Brain Bank for Aging Research (BBAR) in Japan. The investigated anatomical sites followed the Dementia with Lewy Bodies Consensus Guideline, expanding to the peripheral autonomic nervous system, temporal pole, and occipital cortex, in addition to the olfactory epithelium and spinal cord. Of the 32 patients, 11 (34.4%) had Lewy pathology, with a significantly higher prevalence than that in the control cases from the BBAR (20.1%). Lewy pathology detected in DM1 was widespread, but no macroscopic depigmentation of the substantia nigra was observed in any DM1 case; this was commensurate with the microscopic paucity of Lewy pathology in the substantia nigra and amygdala. Lewy pathology in DM1 does not appear to follow either Braak's ascending paradigm or the olfactory–amygdala extension. Lewy neurites and dots in DM1 were very sparse in the cerebral cortex and distinct from those observed in BBAR control cases. This study was the first demonstration of unique Lewy pathology in DM1 and may contribute to the understanding of the protein propagation hypothesis of Lewy pathology. [ABSTRACT FROM AUTHOR]

Aim: Identification of modifiable intrinsic factors for occupational falls is required for initiating effective fall prevention strategies for older workers. This study aimed to identify modifiable intrinsic factors related to falls during occupational activities among older workers. Methods: This retrospective study involved 1164 older workers (aged ≥60 years, workdays ≥4/month) sampled from 18 public employment agencies for seniors in Saitama, Japan. Participants were assessed regarding the following 10 modifiable intrinsic factors: multimorbidity, polypharmacy, fall‐risk‐increasing medication use, self‐rated vision and hearing, functional strength, bilateral stepping, standing balance, executive function and visuospatial ability. The number of falls during occupational activities in the past year was also recorded. Results: In total, 111 falls occurred in 73 of the 1164 participants during occupational activities in the past year. A negative binomial regression model showed that use of fall‐risk‐increasing medications (incidence rate ratio [IRR]: 2.23, 95% confidence interval [CI]: 1.08, 4.60, P = 0.031), reduced functional strength (IRR: 1.81, 95% CI: 1.02, 3.21, P = 0.042), poor standing balance (IRR: 1.83, 95% CI: 1.09, 3.09, P = 0.023) and poor visuospatial ability (IRR: 1.56, 95% CI: 1.03, 2.36, P = 0.034) were independently associated with occupational falls. Conclusions: Our findings suggest that the assessment of medication use, functional strength, standing balance and visuospatial ability in regular health checks in the workplace may be useful for screening older workers at risk of occupational falls. Geriatr Gerontol Int 2022; 22: 338–343. [ABSTRACT FROM AUTHOR]

Background: Taking care of patients with dementia is often stressful and exhausting. The burden placed on caregivers (CGs) for care recipients with dementia (CRDs) has been reported to cause psychological distress.Objective: The aim of this study was to evaluate the psychological distress experienced by CGs for CRDs and identify the sociodemographic factors affecting that distress.Methods: We utilized the 2013 Comprehensive Survey of the Living Conditions for CRDs and CGs. Linked data from 643 pairs of CRDs and CGs were extracted. Serious psychological distress experienced by CGs was measured by Kessler's Psychological Distress scale (K6) with a cutoff point of 13. Factors predictive of psychological distress were evaluated using multivariable logistic regression analysis with the forward selection method.Results: Overall, the mean age of the CGs was 63.5±11.6 years, and 5.3%(34/643) experienced serious psychological distress. Male sex of CRDs, knowing how to access consulting services, spending almost all day for nursing care, and having subjective symptoms within a few days of completing the survey were associated with having serious psychological distress, while older age, participating in shopping as part of the nursing activities, and having their own house were related to freedom from serious psychological distress.Conclusion: Clinicians should be aware of the risk factors for psychological distress in CGs and consider providing support to reduce the distress imposed by modifiable factors. Further studies are warranted to examine whether such efforts would improve the mental health of CGs for CRDs. [ABSTRACT FROM AUTHOR]

Background: Perinatal depression is one of the important mental illnesses among women. However, not enough reviews have been done, and a certain consensus has not been obtained about the prevalence of perinatal depression among Japanese women. The purpose of our study is to reveal the reliable estimates about the prevalence of perinatal depression among Japanese women. Method: We searched two databases, PubMed and ICHUSHI, to identify studies published from January 1994 to December 2017 with data on the prevalence of antenatal or postnatal depression. Data were extracted from published reports. Results: We reviewed 1317 abstracts, retrieved 301 articles and included 123 studies. The point prevalence of postpartum depression at 1 month was 14.3% incorporating 108,431 Japanese women. The period prevalence of depression at pregnancy was 14.0% in the second trimester and 16.3% in the third trimester. The period prevalence of postpartum depression was 15.1% within the first month, 11.6% in 1–3 months, 11.5% in 3–6 months and 11.5% in 6–12 months after birth. We also identified that compared with multiparas, primiparas was significantly associated with a higher prevalence of postpartum depression; the adjusted relative risk was 1.76. Conclusions: The prevalence of postpartum depression at 1 month after childbirth was found to be 14.3% among Japanese women. During pregnancy, the prevalence of depression increases as childbirth approaches, and the prevalence of depression was found to decrease in the postpartum period over time. In addition, we found that the prevalence of postpartum depression in primiparas was higher than that in multiparas. Hence, we suggest that healthcare professionals need to pay more attention to primiparas than multiparas regarding postpartum depression. [ABSTRACT FROM AUTHOR]

Overall early improvement in depression after commencement of antidepressant treatment could be associated with subsequent response or remission, but its predictive ability is not adequate. We aimed to investigate whether early improvement of individual depressive symptoms and important baseline characteristics of patients including the number of previous depressive episodes and the duration of index episode, better predicts response or remission. We requested pharmaceutical companies in Japan for individual patient data from randomized placebo-controlled trials focusing on the efficacy of second-generation antidepressants. Primary and secondary outcomes were response and remission at week 6, respectively. We compared models that only included improvement in the overall depression severity at week 2 with models that also included improvement in individual symptoms and baseline characteristics, by conducting an individual patient data meta-analysis. We obtained data from three trials comprising 997 participants. For the response outcome, the model incorporating individual symptoms and baseline characteristics demonstrated better predictive values than those in the model including early improvement in overall depression only. However, the area under the receiver operating characteristic curve, and positive and negative predictive values were 0.65, 0.70, and 0.64, respectively, suggesting that 30% and 36% of the participants still had false-negative and false-positive predictions, respectively. For the remission outcome, the corresponding values in the latter model were 0.72, 0.62, and 0.68, respectively. We suggest that clinical judgement on early discontinuation of antidepressant from non-early improvement at week 2 should be carefully made. [ABSTRACT FROM AUTHOR]

Background: The prevalence of dementia has increased rapidly in Japan, while the proportion of the population accounted for by working-age individuals is facing a sharp decline. Optimizing the balance between work and caregiving for persons with dementia is a major public health issue. Aims: Using a nationally representative sample, this study investigated the working status of caregivers (CGs) for elderly people (care recipients) with dementia (CRDs) and assessed the effects of sociodemographic factors on this status. Methods: Data were obtained from the 2013 Comprehensive Survey of the Living Conditions for CRDs and CGs (the latter aged 65 years or less). Individual data of CRDs and CGs were linked, and 452 pairs were extracted. The Japanese version of the Kessler 6 (K6) with a cut-off point of 13 was used to assess general psychological distress among CGs. Multivariable logistic regression analysis with the forward selection method was used to identify the predictors of their working status. Results: Overall, the mean age of CGs was 57.1 ± 6.8 years, with 57.5% (260/452) performing paid work. Male sex, higher educational attainment, and having their own house were associated with having paid work for CGs, while higher age, spending almost all day performing nursing care, and participation in helping with toilet activities and laundry were associated with not performing paid work. Conclusions: Several sociodemographic factors, including nursing care-related factors, are associated with the employment status of CGs. Further research should examine detailed information on CRDs' activities of daily living, behavioral and psychological symptoms, medical service use, and social support to strengthen the system of supportive services for both CRDs and their CGs. [ABSTRACT FROM AUTHOR]

Background: The effectiveness of psychotherapeutic interventions for eating disorders (EDs) is widely studied in Europe, North America, and Australia/New Zealand. However, few controlled studies and no randomized controlled trials (RCTs) have been conducted in Japan despite the relatively high prevalence of EDs in the Japanese population. The aim of this study is to evaluate the effect of enhanced cognitive behavior therapy (CBT-E), an evidence-supported ED-focused form of cognitive behavior therapy (CBT), for the treatment of bulimia nervosa (BN) in Japan. Methods/design: This multicenter RCT will compare CBT-E with treatment as usual (TAU), which is widely used in Japan. A group of 140 adult outpatients with a Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) diagnosis of BN, ≥18 years of age, a body mass index (BMI) > 17.5 and < 40 kg/m2 will be randomly assigned to CBT-E or TAU. Participants will be stratified by intervention site and BN severity. CBT-E participants will receive 20 sessions of focused form CBT-E for 20 weeks. Those in the TAU group will receive routine treatment provided by specialists. Assessment will be performed in a blinded manner prior to the start of treatment, after 6 weeks of treatment, at the end of treatment (20 weeks), and at follow-up at 40 and 80 weeks after the start of treatment. The primary outcome is the remission of BN, defined by the absence, in the previous 4 weeks, of symptoms required to meet the DSM-5 criteria for a diagnosis of BN. Secondary outcomes include the levels of ED psychopathology and impairment due to the ED, anxiety, depression, family function, and satisfaction with treatment. Discussion: This will be the first RCT conducted in Japan to compare CBT-E and TAU for the treatment of BN. If CBT-E is found to be more effective than TAU, then the evidence would support its wider use for patients with BN in Japan. Because it is possible to train therapists who do not possess extensive specialist experience, wider use is also likely to be practically feasible. In addition, demonstrating the effectiveness of CBT-E in Japan would demonstrate that it could be successfully extended to additional world cultures and regions. Trial registration: UMIN, UMIN000031625. Registered 7 Mar 2018. [ABSTRACT FROM AUTHOR]

Background: Neuropsychiatric symptoms (NPS) have been recognized as risk factors for conversion to dementia in patients with mild cognitive impairment (MCI). Early detection of NPS may allow for possible interventions in such patients. The present study used mild behavioural impairment to explore the role of NPS in a wide range of patients, from those who are cognitively intact to those with dementia. Methods: A total of 234 patients with mild cognitive impairment were followed up for up to 3 years in a Japanese cohort study. Longitudinal data from patients who developed dementia during the study and those who did not were statistically analyzed. Results: Cox regression analysis revealed that only abnormal perception and thought was significant in terms of dementia conversion. Moreover, mixed‐effects models indicated that baseline mild behavioural impairment symptoms did not affect cognitive trajectories such as changes in Mini‐Mental State Examination or Alzheimer's Disease Assessment Scale‐cognitive subscale scores. Conclusion: We conclude that only abnormal perception and thought content were risk factors for dementia and that NPS may not lead to deterioration of cognitive function in patients with mild cognitive impairment. [ABSTRACT FROM AUTHOR]

Objectives: To examine factors that may affect the use and duration of seclusion and restraint (SR) in psychiatric inpatient settings. Methods: First, multivariable logistic regression analysis was used to examine factors associated with the use of SR in an unmatched case-control study, comparing SR cases and controls. Second, for patients that underwent SR, multivariable linear regression analysis was used to determine factors contributing to the duration of SR. Results: Out of 213 patients, 58 underwent SR. An F00 diagnosis, a history of epilepsy, antipsychotics usage and antidepressants usage were significantly associated with the use of SR (odds ratio = 7.98; 95% CI = 1.11–57.50, odds ratio = 4.89; 95% CI = 1.12–21.36, odds ratio = 4.59; 95% CI = 1.54–13.68 and odds ratio = 0.29; 95% CI = 0.10–0.86, respectively). An F00 and F32 diagnosis significantly extended the duration of SR (coefficient = 13.10; 95% CI = 2.11–24.11 and coefficient = 20.52; 95% CI = 9.68–31.37, respectively). Conclusions: A variety of factors are associated with the use and longer duration of SR. Given the potentially harmful effects of these practices, further studies with larger samples and a wider range of quantitative outcome measures are warranted. An F00 diagnosis, a history of epilepsy and antipsychotics usage may increase the use of SR. Antidepressants may decrease the use of SR. An F00 and F32 diagnosis may extend the duration of SR. [ABSTRACT FROM AUTHOR]

Aims: Pharmacotherapy for methamphetamine dependence has not yet been developed in Japan or elsewhere in the world. Ifenprodil is a blocker of G protein‐activated inwardly rectifying potassium channels that play a key role in the mechanism of action of addictive substances. Our aim is to examine the safety, efficacy, and outcomes of ifenprodil for the treatment of methamphetamine dependence in a randomized, double‐blind, placebo‐controlled trial. Methods: The recruitment of outpatients with methamphetamine dependence began in January 2018. The patients will be randomized into three arms: placebo, 60 mg/d ifenprodil, or 120 mg/d ifenprodil. Placebo or ifenprodil will be taken for 84 days. We will use Cerocral fine granule 4%® (ifenprodil tartrate). Follow‐up assessments will be conducted for 84 d after the drug administration period. All of the patients will be assessed by self‐administered questionnaires and urine tests. The primary outcome will be the presence or absence of methamphetamine use during the 84‐day administration period in the 120 mg/d ifenprodil and placebo groups. Secondary outcomes will include the number of days and percentage of days of abstinence from methamphetamine use, positive urine for methamphetamine, relapse risk, and drug craving. Discussion: This study is the first clinical trial of ifenprodil treatment for methamphetamine dependence and is designed as an intervention test with off‐label drug use. The present study is expected to provide evidence of the effects of ifenprodil treatment on methamphetamine dependence. Trial registry: This trial was registered in the UMIN clinical trial registry (UMIN000030849; date of registration: January 17, 2018). [ABSTRACT FROM AUTHOR]

Background: Several previous studies reported social participation may reduce the incident of dementia; therefore, the type of positions held in the organization may relate to dementia onset. However, this hypothesis remains largely unknown. The purpose of the present study was to examine the additive effect of a leadership position in the organization on dementia onset and social participation among elderly people in a local community, according to data from a Japanese older adults cohort study.Methods: Of 29,374 community-dwelling elderly, a total of 15,313 subjects responded to the baseline survey and were followed-up from November 2003 to March 2013. To evaluate the association between dementia onset and social participation as well as the role in the organization, we conducted Cox proportional hazard regression analysis with multiple imputation by age group (aged 75 years older or younger). The dependent variable was dementia onset, which was obtained from long-term care insurance data in Japan; independent variables were social participation and the role in the organization to which they belonged (head, manager, or treasurer). Covariates were sex, age, educational level, marriage status, job status, residence status, alcohol consumption, smoking status, and walking time, instrumental activities of daily living, depression, and medical history.Results: During the follow-up period, 708 young-old elderly people (7.7%) and 1289 old-old elderly people (27.9%) developed dementia. In young-old elderly, relative to social non-participants, adjusted Hazard Ratio (HR) for dementia onset for participants (regular members + leadership positions) was 0.75 (95% confidence interval (CI), 0.64-0.88). Relative to regular members, adjusted HR for dementia onset for non-participants was 1.22 (95% CI, 1.02-1.46), for leadership positions 0.81 (95% CI, 0.65-0.99). The results for old-old elderly participants did not show that any significantly adjusted HR between dementia onset and social participation, the role in the organization.Conclusions: In young-old elderly people, social participation might have a positive effect on dementia onset, and holding leadership positions in organization could lead to a decrease in risk of dementia onset by almost 20% than regular members. [ABSTRACT FROM AUTHOR]

Introduction: Perinatal depression is a widely discussed mental illness that occurs not only in women, but also in men. A previous international meta-analysis of the prevalence of paternal perinatal depression suggested that cross-cultural variables or socioeconomic environment may influence paternal depression. However, it is not clear that these data are general enough to apply to Japanese men, and there are few review articles about perinatal depression among this demographic. The purpose of our study is to provide a reliable estimate of the prevalence of perinatal depression among Japanese men. Method: We searched two databases, PubMed and ICHUSHI, to identify studies with data on the prevalence of prenatal or postpartum depression among Japanese men. Data were extracted from reports published from January 1994 to June 2018. The period prevalence of paternal perinatal depression among Japanese men was investigated. A subgroup analysis of gender differences in perinatal depression was also performed. Results: We reviewed 1,379 abstracts, retrieved 33 articles and ultimately included 15 studies. The period prevalence of paternal prenatal depression in men was 8.5% (95% CI 3.3–20.3%). Moreover, the period prevalence of postpartum depression in men was 9.7% (95% CI 7.4–12.8%) within the first month, 8.6% (95% CI 5.5–13.3%) in postpartum months 1–3, 13.2% (95% CI 11.6–15.0%) in postpartum months 3–6 and 8.2% (95% CI 1.3–38.0%) in postpartum months 6–12. We also found that the prevalence of prenatal depression was significantly lower in men than in women. However, the prevalence of postpartum depression was not significantly different between men and women. Conclusions: The prevalence of perinatal depression among Japanese men peaked at 3–6 months after birth, and its overall prevalence was approximately 10%. These results were similar to those of an international meta-analysis on perinatal depression. Notably, we found that the prevalence of postpartum depression was as high in men as it was in women. Therefore, it is suggested that healthcare workers should be more watchful for paternal perinatal depression in the postpartum period than in the prenatal period. [ABSTRACT FROM AUTHOR]

Background: There is growing evidence of the treatment efficacy of cognitive behavioral therapy (CBT) for irritable bowel syndrome (IBS). CBT is recommended by several practice guidelines for patients with IBS if lifestyle advice or pharmacotherapy has been ineffective. Manual-based CBT using interoceptive exposure (IE), which focuses on the anxiety response to abdominal symptoms, has been reported to be more effective than other types of CBT. One flaw of CBT use in general practice is that it is time and effort consuming for therapists. Therefore, we developed a set of complementary video materials that include psycho-education and homework instructions for CBT patients, reducing time spent in face-to-face sessions while maintaining treatment effects. The purpose of this study is to examine the effects of CBT-IE with complementary video materials (CBT-IE-w/vid) in a multicenter randomized controlled trial (RCT). Methods: This study will be a multicenter, parallel-design RCT. Participants diagnosed with IBS according to the Rome IV diagnostic criteria will be randomized to either the treatment as usual (TAU) group or the CBT-IE-w/vid + TAU group. CBT-IE-w/vid consists of 10 sessions (approximately 30 min face-to-face therapy + viewing a video prior to each session). Patients in the CBT-IE-w/vid group will be instructed to pre- view 3- to 13-min videos at home prior to each face-to-face therapy visit at a hospital. The primary outcome is the severity of IBS symptoms. All participants will be assessed at baseline, mid-treatment, post-treatment, and follow-up (3 months after post assessment). The sample will include 60 participants in each group. Discussion: To our knowledge, this study will be the first RCT of manual-based CBT for IBS in Japan. By using psycho-educational video materials, the time and cost of therapy will be reduced. Manual based CBTs for IBS have not been widely adopted in Japan to date. If our CBT-IE-w/vid program is confirmed to be more effective than TAU, it will facilitate dissemination of cost-effective manual-based CBT in clinical settings. Trial registration: The trial was registered to the University Hospital Medical Information Network Clinical Trial Registry: UMIN, No. UMIN000030620 (Date of registration: December 28, 2017). [ABSTRACT FROM AUTHOR]

A prospective multicenter registry study was started May 2016 in Japan to evaluate the efficacy and safety of proton beam therapy (PBT) for hepatocellular carcinoma (HCC). Patients who received PBT for HCC from May 2016 to June 2018 were registered in the database of the Particle Beam Therapy Committee and Subcommittee of the Japanese Society for Radiation Oncology. Overall survival (OS), progression-free survival (PFS), and local recurrence were evaluated. Of the 755 registered patients, 576 with initial PBT and no duplicate cancer were evaluated. At final follow-up, 322 patients were alive and 254 had died. The median follow-up period for survivors was 39 months (0-58 months). The median OS time of the 576 patients was 48.8 months (95% CI, 42.0-55.6 months) and the 1-, 2-, 3-, and 4-year OS rates were 83.8% (95% CI, 80.5%-86.6%), 68.5% (64.5%-72.2%), 58.2% (53.9%-62.2%), and 50.1% (44.9%-55.0%), respectively. Recurrence was observed in 332 patients, including local recurrence in 45 patients. The median PFS time was 14.7 months (95% CI, 12.4-17.0 months) and the 1-, 2-, 3-, and 4-year PFS rates were 55.2% (95% CI, 51.0%-59.2%), 37.5% (33.5%-41.5%), 30.2% (26.3%-34.2%), and 22.8% (18.5%-27.4%), respectively. The 1-, 2-, 3-, and 4-year OS rates were significantly higher for tumor size <5 versus 5 to 10 cm (P <.001) and <5 versus ≥10 cm (P <.001); Child-Pugh score A/B versus C (P <.001); and distance of the tumor from the gastrointestinal tract <1 versus 1 to 2 cm (P <.008) and <1 versus >2 cm (P <.001). At final follow-up, 27 patients (4.7%) had late adverse events of grade 3 or higher, with liver failure (n = 7), and dermatitis (n = 7) being most common. This multicenter prospective data registry indicated that PBT for HCC gives good therapeutic effects (3-year local control rate of 90%) with a low risk of severe late adverse events. [ABSTRACT FROM AUTHOR]

Background: It is clinically important to know who are likely to respond more or less to antidepressants. However, meaningful effect modifiers (variables associated with differential response depending on the treatment) are yet to be identified.Methods: We conducted individual participant data (IPD) meta-analysis and meta-regression to explore effect modifiers in placebo-controlled antidepressant trials conducted so far in Japan.Results: We obtained access to IPD from seven placebo-controlled trials comparing bupropion, duloxetine, escitalopram, mirtazapine, paroxetine or venlafaxine with placebo in the acute phase treatment of major depression (total n = 2803). The higher the guilt subscale score of the baseline Hamilton Rating Scale for Depression (HRSD), the greater the difference in reduction in depression severity between the antidepressants and placebo at week 6, while the older the current age or the age at onset, the smaller the difference. At week 8, the guilt subscale score of HRSD and presence of suicidal ideation at baseline predicted greater, and the anhedonia subscale and insomnia subscale scores of HRSD and early response at week 2 predicted smaller, difference in reduction.Limitations: Different studies measured different sets of baseline variables and we were able to analyze only a limited set of candidate variables for effect modification.Conclusion: Age, age at onset, several HRSD subscales including guilt, anhedonia and insomnia, presence of suicidal ideation at baseline and early response are potential effect modifiers for response to antidepressants in the acute phase antidepressant treatment of major depression. Future trials need to measure these and additional variables in concerted efforts to enable matching of treatments with individual characteristics in depression. [ABSTRACT FROM AUTHOR]

Objective: The diagnosis of childhood‐onset cerebellar ataxia (CA) is often challenging due to variations in symptoms and etiologies. Despite the known regional differences in the prevalence of etiologies underlying CA, the frequency and characteristics of CA in Japan remain unclear. We conducted a questionnaire‐based survey to identify the clinical characteristics of childhood‐onset CA in the Japanese population. Materials and Methods: Questionnaires were sent to 1,103 board‐certified pediatric neurologists in Japan from 2016 to 2017. The primary survey requested the number of patients with CA under care, and the follow‐up secondary questionnaire requested additional clinical characteristics of the patients. Results: The primary survey obtained 578 responses (response rate, 52.4%) on 385 patients with CA, including 171 diagnosed and 214 undiagnosed cases (diagnostic rate, 44.4%). The most frequent etiology was dentatorubropallidoluysian atrophy (DRPLA), followed by mitochondrial disorders and encephalitis. The secondary survey obtained the clinical characteristics of 252 cases (119 diagnosed and 133 undiagnosed cases). Multiple logistic regression analysis revealed that a younger age at onset, hearing issues, and short stature were associated with a higher risk of remaining undiagnosed with CA in Japan. Conclusions: The diagnostic rate of childhood‐onset CA in the current study was comparable to those reported in other countries. The high prevalence of autosomal dominant ataxia, especially DRPLA, was a signature of CA in Japan. These data offer insights into the characteristics of childhood‐onset CA in the Japanese population. [ABSTRACT FROM AUTHOR]

• Frailty is a risk factor for insomnia, insomnia is also a risk factor for frailty. • Insomnia and frailty were equally associated with each other in all participants. • The primary potential cause of the association varied by sex. • Effect of frailty on insomnia was stronger than that of insomnia on frailty in men. • Impact of insomnia on frailty was greater than that of frailty on insomnia in women. Most previous studies that examined the association of insomnia with frailty used cross-sectional designs. The temporal relationship between these factors is therefore largely unknown. This study aimed to examine the bidirectional relationship between insomnia and frailty by sex. A 2-year longitudinal study involving all community-dwelling older adults living in a rural area in Japan (n = 3844). Validated measures of insomnia and frailty were employed. Insomnia was assessed using the Athens insomnia scale, and frailty using the Kihon checklist. We performed a cross-lagged panel model, adjusted for age, sex, years of education, employment status, self-rated health, complications (hypertension, diabetes, stroke, or osteoarthritis), BMI, physical activity, alcohol consumption, and smoking status, and assessed differences by sex. Poor sleep predicted the onset and worsening of frailty during follow up (standardized coefficient [95% confidence interval]: 0.076 [0.045, 0.107]). Frailty also predicted severe insomnia symptoms (0.074 [0.044, 0.104]). However, the temporal association between these conditions varied by sex. In older men, the effect of frailty on insomnia was stronger than that of insomnia on frailty. However, in women, the impact of insomnia on frailty was stronger than that of frailty on insomnia. The primary potential cause of the association between insomnia and frailty may vary by sex, being frailty in men and insomnia in women. Sex-specific interventions to improve sleep quality and duration, and maintain functional abilities in daily life may contribute to the prevention and management of both frailty and insomnia in older adults. [ABSTRACT FROM AUTHOR]

• Declines in physical activity (PA) were observed during the follow-up. • Social group engagement (SGE) helps to suppress age-related decline in PA. • Consistent and new engagement contribute to maintaining total and moderate PA. • No difference in PA change between consistent engagement and dropping out. • No type of SGE mitigated the decrease in vigorous PA in older age. Although social group engagement (SGE) has been suggested to affect physical activity (PA) in older age, the longitudinal relationship between these variables is unclear. This study used 2-year panel data to investigate the link between changes in SGE and changes in PA among community-dwelling older adults. This study was a 2-year community-based longitudinal study enrolling older adults living in a rural municipality in Japan. The subjects were all residents in the study area aged ≥ 65 at the baseline. Mail surveys were administered in 2016 and 2018. The 3688 subjects responding to both surveys were included in the analyses. PA was evaluated with the International Physical Activity Questionnaire, and weekly time and metabolic equivalent were computed. SGE was assessed in each wave and classified as consistent engagement (engagement reported in both surveys), new engagement (non-engagement at baseline and engagement at follow-up), leaving the group (engagement at baseline and non-engagement at follow-up), and consistent non-engagement (non-engagement in both surveys). Analysis of covariance was performed to examine the associations of changes in SGE with changes in PA. Compared with those with consistent non-engagement, who showed declines in every PA category, subjects with consistent engagement or new engagement showed significantly smaller changes in total PA, moderate-intensity PA, and brisk walking. Leaving the group (vs. consistent non-engagement) was associated with maintaining moderate-intensity PA. SGE helps to suppress the age-associated decline in PA in older age, with new engagement and continuous engagement, especially, mitigating decreasing PA. [ABSTRACT FROM AUTHOR]

Background: Radio-Taiso, a long-standing exercise program in Japan, could be a sustainable public health strategy for maintaining quality of life (QoL) in older adults with frailty. This study aimed to investigate whether Radio-Taiso provided greater benefits for health-related quality of life (HRQoL) and to identify the mechanisms underlying the effectiveness in this population., Methods: A 12-week randomized controlled trial enrolled 226 older Japanese adults with pre-frailty or frailty, assessed using the modified frailty phenotype. Participants were randomly allocated to the intervention (Radio-Taiso + nutrition program) or control (nutrition program) groups. The Radio-Taiso program comprised five 60-min group sessions and daily practice at the participants' homes. The primary outcome was the change in the mental domain of HRQoL, assessed using the SF-36 ® . The secondary outcomes included six physical fitness items and exercise self-efficacy., Results: Overall, 104 and 105 participants in the intervention and control groups, respectively, were analyzed based on the intention-to-treat principle. The median daily practice rate of Radio-Taiso was 94.1% (interquartile range, 73.2-98.8%). Although general linear models adjusted for baseline values and allocation stratification factors showed that the intervention group obtained greater benefits (adjusted mean differences) in the up-and-go (0.3; 95% confidence interval [CI], 0.1 to 0.6 s), 2-min step-in-place (-3.2; 95% CI, -6.2 to -0.2 steps) tests, and exercise self-efficacy scale (-1.4; 95% CI, -2.6 to -0.1 points) than the control group, there were no group differences in changes in the mental domain score of HRQoL., Conclusion: Radio-Taiso provided greater benefits for agility/dynamic balance, aerobic endurance, and exercise self-efficacy in older adults with frailty; however, these changes do not improve HRQoL.

Background: Proton-based, definitive chemoradiotherapy (P-CRT) for esophageal squamous cell carcinoma (ESCC) previously showed comparable survival outcomes with the surgery-based therapy, i.e., neoadjuvant chemotherapy followed by esophagectomy (NAC-S), in a single-institutional study. This study aimed to validate this message in a Japanese multicenter study., Methods: Eleven Japanese esophageal cancer specialty hospitals have participated. A total of 518 cases with clinical Stage I-IVA ESCC between 2010 and 2019, including 168 P-CRT and 350 NAC-S patients, were enrolled and long-term outcomes were evaluated. Propensity-score weighting analyses with overlap weighting for confounding adjustment were used., Results: The 3-year overall survival (OS) of the P-CRT group was equivalent to the NAC-S group (74.8% vs. 72.7%, hazard ratio [HR]: 0.87, 95% confidence interval [CI]: 0.61-1.25). Although, the 3-year P-CRT group progression-free survival (PFS) was inferior to the NAC-S group (51.4% vs. 59.6%, HR 1.39, 95% CI 1.04-1.85), the progression P-CRT group cases showed better survival than the NAC-S group (HR 0.58, 95% CI 0.38-0.88), largely because of salvage surgery or endoscopic submucosal dissection for local progression. The survival advantage of P-CRT over NAC-S was more pronounced in the cT1-2 (HR 0.61, 95% CI 0.29-1.26) and cStage I-II (HR 0.50, 95% CI 0.24-1.07) subgroups, although this trend was not evident in other populations, such as cT3-4 and cStage III-IVA., Conclusions: Proton-based CRT for ESCC showed equivalent OS to surgery-based therapy. Especially for patients with cT1-2 and cStage I-II disease, proton-based CRT has the potential to serve as a first-line treatment., (© 2024. The Author(s), under exclusive licence to The Author(s) under exclusive licence to The Japan Esophageal Society.)

Background: To evaluate the seasonal variability of urinary albumin to creatinine ratio (UACR) and eGFR and these effects on three-year eGFR slope in persons with type 2 diabetes (T2D)., Methods: A total of 1135 persons with T2D were analyzed in this single-center, retrospective cohort study in Japan. The standard deviation (SD) of UACR (SD [UACR]) and SD of eGFR (SD [eGFR]) were calculated for each person's 10-point data during the three years, and a multiple linear regression analysis was performed to evaluate associations with eGFR slope. A sensitivity analysis was performed in a group with no medication changes (n = 801)., Results: UACR exhibited seasonal variability, being higher in winter and lower in spring, early summer, and autumn especially in the UACR ≥ 30 mg/g subgroup, while eGFR showed no seasonal variability. The eGFR slope was significantly associated with SD (eGFR) (regression coefficient -0.170 [95% CI -0.189--0.151]) and SD (UACR) (0.000 [-0.001-0.000]). SGLT-2 inhibitors, baseline eGFR, and baseline systolic blood pressure (SBP) were also significantly associated. These associated factors, except baseline SBP, were still significant in the sensitivity analysis., Conclusions: The UACR showed clear seasonal variability. Moreover, SD (UACR) and SD (eGFR) were independently associated with a three-year eGFR slope in persons with T2D., Trial Registration: This study was not registered for clinical trial registration because it was a retrospective observational study., (© 2024. The Author(s).)

Objectives: Poor cardiorespiratory fitness (CRF) and high body mass index (BMI) increased the risk of developing metabolic Syndrome (MetS) mostly in Caucasians. However, the sex-specific combined association of CRF and BMI on MetS considering health-related behaviors has yet to be thoroughly examined in Japanese. This study aims to investigate the sex-specific independent and combined associations of CRF and BMI with MetS in middle-aged Japanese adults., Methods: 421 participants were included in this cross-sectional study. CRF was estimated using a submaximal cycle ergometer. CRF and BMI were respectively divided into three categories according to tertile distribution. MetS was diagnosed based on five risk factors: waist circumference, triglycerides, high-density lipoprotein cholesterol, blood pressure, and fasting glucose. Multivariable logistic regression models were used to estimate independent and combined association of CRF and BMI with MetS., Results: Results showed that 154 (57.5%) and 70 (45.8%) of men and women had MetS, respectively. Compared to men with lower CRF or higher BMI, men with middle and higher CRF or middle and lower BMI were less likely to have MetS. Compared with 'unfit and higher BMI' group, 'unfit and lower BMI', 'fit and higher BMI', and 'fit and lower BMI' groups in men showed statistically significant decreased prevalences of MetS. However, no significant associations were found in women., Conclusions: This study found significant independent and combined associations of CRF and BMI with MetS only in men, but not in women. However, prospective studies are warranted to confirm sex-specific associations of CRF and BMI with MetS., (© 2024. The Author(s).)

Background: It has not been determined whether mentally active sedentary behavior (MASB) and passive sedentary behavior (PSB) differentially affect cognitive function and whether these associations differ according to physical activity (PA) level. We examined the comparative impacts of MASB and PSB on dementia onset and aimed to understand whether the associations differed by PA level., Methods: We conducted a 5-year longitudinal study involving all community-dwelling older adults in a rural area in Japan (n = 5,323). Dementia onset was examined using long-term care insurance data. PA was evaluated using the International Physical Activity Questionnaire and categorized as low (<2.5 metabolic equivalent of task [MET]-h/week), moderate (2.5-16.0 MET-h/week), or high (≥16.0 MET-h/week). We also assessed PSB (TV-watching time; <1 h/day, 1-3 h/day, ≥3 h/day) and MASB (Book-reading time; <10 min/day, 10-30 min/day, ≥30 min/day). To examine the associations of MASB and PSB with dementia onset, we performed the Fine-Gray models accounting for competing risk of death., Results: During the follow-up period, 606 (11.4%) participants developed dementia. MASB was independently associated with a lower risk of dementia; the magnitude of the impact was significant at higher PA levels. There was no association between PSB and developing dementia across all PA levels. Furthermore, dementia risk for individuals with high PA levels and moderate or high MASB levels was approximately 60% lower than those with low PA levels and low MASB., Conclusion: Providing interventions to promote MASB, which reduces dementia risk, and PA, which increases MASB's effect on dementia incidence, can be beneficial in delaying or preventing dementia onset.

Background: Logistic regression models are widely used to evaluate the association between a binary outcome and a set of covariates. However, when there are few study participants at the outcome and covariate levels, the models lead to bias of the odds ratio (OR) estimated using the maximum likelihood (ML) method. This bias is known as sparse data bias, and the estimated OR can yield impossibly large values because of data sparsity. However, this bias has been ignored in most epidemiological studies., Methods: We review several methods for reducing sparse data bias in logistic regression. The primary aim is to evaluate the Bayesian methods in comparison with the classical methods, such as the ML, Firth's, and exact methods using a simulation study. We also apply these methods to a real data set., Results: Our simulation results indicate that the bias of the OR from the ML, Firth's, and exact methods is considerable. Furthermore, the Bayesian methods with hyper-ɡ prior modeling of the prior covariance matrix for regression coefficients reduced the bias under the null hypothesis, whereas the Bayesian methods with log F-type priors reduced the bias under the alternative hypothesis., Conclusion: The Bayesian methods using log F-type priors and hyper-ɡ prior are superior to the ML, Firth's, and exact methods when fitting logistic models to sparse data sets. The choice of a preferable method depends on the null and alternative hypothesis. Sensitivity analysis is important to understand the robustness of the results in sparse data analysis.

Objectives: To clarify the association between moderate-to-vigorous physical activity (MVPA) and/or sedentary behaviour (SB) and the incidence of functional disability (FD) in older adults., Design: Prospective cohort study., Setting: Local municipality of Tsuru, Yamanashi, Japan. We conducted a baseline survey in January 2016. Follow-up was commenced on 1 February 2016 and completed on 31 October 2018., Participants: All individuals (6661 people) aged >65 years who were independently living in the community were eligible., Methods and Outcome Measures: MVPA (min/week) and SB (min/day) were measured using self-administered questionnaires in 5311 independently living older adults who participated in this study. The follow-up period was 33 months, and the incidence of FD was objectively determined by experts. The participants were divided into three groups based on MVPA distribution (non-MVPA, 0 min; short-MVPA, 1-299 min and long-MVPA, ≥300 min/week) and into two groups based on the median value of SB (short-SB,<190 min; and long-SB, ≥190 min/day). The participants were also classified into six categories based on different combinations of MVPA and SB. Cox proportional hazards model was used to calculate the HR and 95% CI for FD development with MVPA, SB and a combination of these behaviours., Results: Among the included participants, 2415 were male and 2896 were female. The mean ages (SD) of the male and female participants were 74.5 (6.8) and 74.9 (6.9) years, respectively. The total number of participants with chronic conditions was 3489 (65.7%). Using the non-MVPA group as the reference, the multivariable-adjusted HR (95% CI) was 0.68 (0.54 to 0.84) in the short-MVPA group and 0.53 (0.41 to 0.69) in the long-MVPA group. Regarding SB, the short-SB group had an HR of 0.86 (0.71 to 1.03) compared with the long-SB group. The combined behaviour showed the lowest HR in the long-MVPA and short-SB group 0.49 (0.34 to 0.72) and the long-MVPA and long-SB group 0.49 (0.34 to 0.68), respectively., Conclusions: Long-MVPA had a robust association with FD development, whereas short-SB had a modest association. Moreover, a combination of these behaviours had a stronger association than individual behaviours. If the identified associations are assumed to be causal in nature, these findings suggest that encouraging older adults to engage in MVPA and reduce SB in their daily lives could be effective to prevent or delay FD development., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Status epilepticus (SE) is an emergency condition for which rapid and secured cessation is important. Phenytoin and fosphenytoin, the prodrug of phenytoin with less severe adverse effects, have been recommended as second-line treatments. However, fosphenytoin causes severe adverse events, such as hypotension and arrhythmia. Levetiracetam reportedly has similar efficacy and higher safety for SE; however, evidence to support its use for adult SE is lacking. In the present study, a non-inferiority designed multicenter randomized controlled trial (RCT) is being conducted to compare levetiracetam with fosphenytoin after diazepam as a second-line treatment for SE., Methods: This multicenter, prospective, and open-label RCT is conducted in emergency departments. Between December 23, 2019, and March 31, 2023, 176 patients with convulsive SE transported to an emergency room will be randomized into a fosphenytoin group and levetiracetam group at a ratio of 1:1. The definition of SE is "continuous seizures longer than 5 min or discrete seizures longer than 2 min with intervening consciousness disturbance." In both groups, diazepam is initially administered at 1-20 mg, followed by intravenous fosphenytoin at 22.5 mg/kg or intravenous levetiracetam at 1000-3000 mg. The primary outcome is the seizure cessation rate within 30 min. Seizure recurrence within 24 h, severe adverse events, and intubation rate within 24 h are secondary outcomes., Discussion: The present study was approved and conducted as an initiative study of the Japanese Association for Acute Medicine. If non-inferiority is identified, the society will pursue an application for the national health insurance coverage of levetiracetam for SE via a public knowledge-based application., Trial Registration: Japan Registry of Clinical Trials jRCTs031190160 . Registered on December 13, 2019.

Introduction: Transcranial direct current stimulation (tDCS) is a potentially novel strategy for cognitive enhancement in patients with disorders. We present a study protocol for a randomised controlled trial designed to evaluate the safety and efficacy of tDCS combined with cognitive tasks on cognition in such patients., Method and Analysis: This is a two-arm, parallel-design, randomised, sham-controlled trial, in which participants and raters will be blinded at a single centre. Stratified randomisation will be conducted, and a randomisation sequence will be generated through the Electronic Data Capture system. Patients who met the Diagnostic and Statistical Manual of Mental Disorders-5 criteria for neurocognitive disorders will be recruited and randomised to receive either active (2 mA for 20 min) or sham (stimulation ramped up and down for 1 min) stimulation in 10 sessions over five consecutive days. A direct current will be transferred by a 35 cm 2 saline-soaked sponge electrode. An anode will be placed over the left dorsolateral prefrontal cortex, and a cathode will be placed over the right supraorbital cortex. Calculation tasks will be conducted in both arms as a cognitive task for 20 min during the stimulation. This task consists of basic arithmetic questions, such as single-digit addition, subtraction, multiplication and division. The primary outcome will be the mean change in the Alzheimer Disease Assessment Scale-cognition at Day 5 after baseline. Depressive symptoms, as measured by the geriatric depression scale, and quality of life, as measured by the Medical Outcomes Study 36-item Short-Form Health Survey, will also be assessed. Data will be collected at baseline, within 3 days following the final stimulation and 1 month thereafter. The estimated sample size is 46 per group based on the assumptions that an estimated mean difference is -1.61 and SD is 2.7. Mixed models for repeated measures will be used for the statistical analysis., Ethics and Dissemination: The National Center of Neurology and the Psychiatry Clinical Research Review Board (CRB3180006) approved this study. The results of this study will be published in a scientific peer-reviewed journal., Trial Registration Details: Japan Registry of Clinical Trials jRCTs032180016., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Assessment of sensory impairment in diabetic patients by pain threshold test using intraepidermal electrical stimulation (IES) is a recently developed technique. However, there are no normative pain thresholds in healthy people., Methods: We examined pain, vibration, and pressure thresholds in 178 healthy subjects using IES, vibration perception testing (VPT), and Semmes-Weinstein monofilament testing (SWMT)., Results: The mean values for each age group for pain threshold ranged from 0.07 to 0.12 mA. Pain thresholds were unaffected by age. As the age increased, VPT values decreased from 18.0 to 10.6 seconds and SWMT values increased from 21.4 to 45.3 g/mm 2 . There were no significant differences in pain threshold, VPT, and SWMT between men and women., Discussion: The pain threshold test appears to be useful for diabetic neuropathy screening because normative values are not affected by age., (© 2020 Wiley Periodicals, Inc.)

Background: Identifying potential placebo responders among apparent drug responders is critical to dissect drug-specific and nonspecific effects in depression., Objective: This project aimed to develop and test a prediction model for the probability of responding to placebo in antidepressant trials. Such a model will allow us to estimate the probability of placebo response among drug responders in antidepressants trials., Methods: We identified all placebo-controlled, double-blind randomised controlled trials (RCTs) of second generation antidepressants for major depressive disorder conducted in Japan and requested their individual patient data (IPD) to pharmaceutical companies. We obtained IPD (n=1493) from four phase II/III RCTs comparing mirtazapine, escitalopram, duloxetine, paroxetine and placebo. Out of 1493 participants in the four clinical trials, 440 participants allocated to placebo were included in the analyses. Our primary outcome was response, defined as 50% or greater reduction on Hamilton Rating Scale for Depression at study endpoint. We used multivariable logistic regression to develop a prediction model. All available candidate of predictor variables were tested through a backward variable selection and covariates were selected for the prediction model. The performance of the model was assessed by using Hosmer-Lemeshow test for calibration and the area under the ROC curve for discrimination., Findings: Placebo response rates differed between 31% and 59% (grand average: 43%) among four trials. Four variables were selected from all candidate variables and included in the final model: age at onset, age at baseline, bodily symptoms, and study-level difference. The final model performed satisfactorily in terms of calibration (Hosmer-Lemeshow p=0.92) and discrimination (the area under the ROC curve (AUC): 0.70)., Conclusions: Our model is expected to help researchers discriminate individuals who are more likely to respond to placebo from those who are less likely so., Clinical Implications: A larger sample and more precise individual participant information should be collected for better performance. Examination of external validity in independent datasets is warranted., Trial Registration Number: CRD42017055912., Competing Interests: Competing interests: TAF has received lecture fees from Janssen, Meiji, Mitsubishi-Tanabe, MSD and Pfizer and research support from Mitsubishi-Tanabe; HN has received lecture fees from Boehringer Ingelheim and Kyowa Hakko Kirin, and research support from Kyowa Hakko Kirin and GSK. HI reports lecture fees from Mitsubishi-Tanabe, personal fees from Medical Science International publisher. ST has received lecture fees from Astra-Zeneca, Taiho and Ono. He has received consultation fees from DeNA Life Science and CanBus. He has received outsourcing fees from Satt and Asahi Kasei Pharma. His wife has been engaged in a research project of Bayer. AC is the Editor for BMJ Evidence-Based Medicine., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Fukuyama congenital muscular dystrophy (FCMD) is the second most common form of muscular dystrophy in the Japanese population and is caused by mutations in the fukutin (FKTN) gene. In 2011, the Japan Muscular Dystrophy Association (JMDA) developed a nationwide registry of genetically confirmed patients with FCMD. We retrospectively reviewed the registry dataset of patients with FCMD to obtain data, including age, sex, developmental milestones, intellectual level, complications, and primary treatments. In total, 207 patients with FCMD (104 boys and 103 girls) were registered by the end of September 2013. Mean patient age at first registration was 8.1 ± 7.8 years (median, 6 years; range, 0-42 years). A homozygous 3-kb founder insertion mutation in the FKTN gene was present in 80% of registrants, whereas 20% had a compound heterozygous mutation. Sixty-nine patients (33%) had febrile seizures and/or epilepsy. Myopia was the most frequently detected abnormality (8.7%), followed by strabismus (5.9%). Overall, 16% of patients required respiratory support and this percentage increased with age. Cardiac dysfunction was detected in 16%, and dysphagia was observed in 22% of patients with FCMD. The FCMD patient registry is useful for clarifying the natural history of FCMD and recruiting patients for clinical trials., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aim: Identifying factors that influence participation in social group activities in older adults might be helpful in promoting social participation in this population. We examined factors related to new or continuous participation in social group activities according to group type., Methods: We carried out a community-based, longitudinal study with a 2-year follow-up period. Of 7608 older adults aged ≥65 years, 3380 completed the follow-up survey and were included in the analysis. We examined private group (hobbies, sports and volunteering; PrG) and public group (neighborhood associations and senior citizen clubs; PuG) activity., Results: For PrG, 39.6% of the participants were engaged at baseline, 25.5% initiated participation and 9.5% withdrew during the study period. For PuG, 20.8% of the participants were engaged at baseline, 10.8% initiated participation and 31.5% withdrew during the study period. Logistic regression analysis showed mental health, self-rated health, employment, relationships with neighbors, subjective economic status, educational attainment and participation in PuG were related to new participation in PrG. Mental health, employment and relationships with neighbors were significantly related to continuous participation. For PuG, mental health, sex and relationships with neighbors were significantly related to new participation, whereas sex, relationships with neighbors and educational attainment were related to continuous participation., Conclusions: The rate of new and continuous participation in PrG was higher than that in PuG, and different related factors were identified as existing between social group types. Geriatr Gerontol Int 2018; 18: 1259-1266., (© 2018 Japan Geriatrics Society.)