Efficacy and Safety of Cilostazol in Mild Cognitive Impairment: A Randomized Clinical Trial.

Importance: Recent evidence indicates the efficacy of ß-amyloid immunotherapy for the treatment of Alzheimer disease, highlighting the need to promote ß-amyloid removal from the brain. Cilostazol, a selective type 3 phosphodiesterase inhibitor, promotes such clearance by facilitating intramural periarterial drainage. Objective: To determine the safety and efficacy of cilostazol in mild cognitive impairment. Design, Setting, and Participants: The COMCID trial (A Trial of Cilostazol for Prevention of Conversion from Mild Cognitive Impairment to Dementia) was an investigator-initiated, double-blind, phase 2 randomized clinical trial. Adult participants were registered between May 25, 2015, and March 31, 2018, and received placebo or cilostazol for up to 96 weeks. Participants were treated in the National Cerebral and Cardiovascular Center and 14 other regional core hospitals in Japan. Patients with mild cognitive impairment with Mini-Mental State Examination (MMSE) scores of 22 to 28 points (on a scale of 0 to 30, with lower scores indicating greater cognitive impairment) and Clinical Dementia Rating scores of 0.5 points (on a scale of 0, 0.5, 1, 2, and 3, with higher scores indicating more severe dementia) were enrolled. The data were analyzed from May 1, 2020, to December 1, 2020. Interventions: The participants were treated with placebo, 1 tablet twice daily, or cilostazol, 50 mg twice daily, for up to 96 weeks. Main Outcomes and Measures: The primary end point was the change in the total MMSE score from baseline to the final observation. Safety analyses included all adverse events. Results: The full analysis set included 159 patients (66 [41.5%] male; mean [SD] age, 75.6 [5.2] years) who received placebo or cilostazol at least once. There was no statistically significant difference between the placebo and cilostazol groups for the primary outcome. The least-squares mean (SE) changes in the MMSE scores among patients receiving placebo were -0.1 (0.3) at the 24-week visit, -0.8 (0.3) at 48 weeks, -1.2 (0.4) at 72 weeks, and -1.3 (0.4) at 96 weeks. Among those receiving cilostazol, the least-squares mean (SE) changes in MMSE scores were -0.6 (0.3) at 24 weeks, -1.0 (0.3) at 48 weeks, -1.1 (0.4) at 72 weeks, and -1.8 (0.4) at 96 weeks. Two patients (2.5%) in the placebo group and 3 patients (3.8%) in the cilostazol group withdrew owing to adverse effects. There was 1 case of subdural hematoma in the cilostazol group, which may have been related to the cilostazol treatment; the patient was successfully treated surgically. Conclusions and Relevance: In this randomized clinical trial, cilostazol was well tolerated, although it did not prevent cognitive decline. The efficacy of cilostazol should be tested in future trials. Trial Registration: ClinicalTrials.gov Identifier: NCT02491268.

Tooth Loss as a Predictor of Long-Term Care Requirements in the Elderly: A Study in Kobe City, Japan.

INTRODUCTION: The Kobe project, which utilizes prospective data from the national health insurance system, focuses on early detection and preventive strategies through the Frail Kenshin health check-up program. Previous research has underscored the correlation between tooth loss and the decline in physical and cognitive functions. In this study, using Kobe project data, we examined the link between remaining teeth and long-term care needs in individuals aged 64-65 years, with primary and secondary objectives involving various health parameters and quality of life. METHODS: We analyzed baseline data from a prospective study conducted alongside the Frail Check program for generally healthy individuals aged 64-65 years to examine the relationship between the number of remaining teeth and various health indicators. This study focused on citizens aged 64-65 years to identify those at risk of needing long-term care by the age of 65 years. RESULTS: Data from 1,530 participants were obtained, excluding eight individuals for specific reasons. At the end of the follow-up period, 41 (2.7%) individuals required support and 15 (1.0%) needed long-term care alone. The data revealed a significant association between the number of remaining teeth and the need for long-term care or support, as demonstrated by the Cochran-Armitage trend test (p<0.001). Although trends were noted for nutrition and total Cognitive Functional Instrument Self scores, they did not reach statistical significance. Additionally, a decrease in the number of remaining teeth was significantly associated with worse European Quality of Life Five Dimensions (EQ-5D-5L) visual analog scale scores, mobility, and regular activities (p<0.001). CONCLUSION: Tooth loss indicates the potential long-term care needs of older adults. Monitoring oral health is crucial for addressing care requirements.

Early Detection of Dementia using Risk Classification in MCI: Outcomes of Shanghai Mild Cognitive Impairment Cohort Study.

INTRODUCTION: The purpose of this study is to identify the risk factors and risk classification associated with the conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD) dementia to facilitate early intervention and the design of clinical trials for AD. METHODS: The study comprised a prospective cohort study of 400 subjects with MCI who had annual follow-ups for 3 years. RESULTS: During an average follow-up period of 3.5 years, 109 subjects were diagnosed with all cause of dementia, of whom 104 subjects converted to Alzheimer's dementia and 5 subjects converted to other types of dementia. The cumulative conversion rate was 5.5% (95% CI: 3.4, 8.6), 16.3% (95% CI: 12.9, 21.1), and 31.0% (95% CI: 25.4, 36.5) in each of the first 3 follow-up years, respectively. The factors associated with a greater risk of conversion from MCI to AD included smoking status, ApoE4 carrier status, right hippocampal volume (rt. HV), left temporal lobe volume, and scores on the Revised Chinese version of the Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog-C). The risk classification of the ADAS-Cog-C or Preclinical Alzheimer Cognitive Composite (PACC) score combined with the rt. HV showed a conversion difference among the groups at every annual follow-up. CONCLUSION: A simple risk classification using the rt. HV and neuropsychological test scores, including those from the ADAS-Cog-C and PACC, could be a practicable and efficient approach to indentify individuals at risk of all-cause dementia.

The prognosis of patients with prostate cancer receiving permanent seed implantation stratified by prostate volume: Should we be reluctant to treat with brachytherapy because of a very small prostate (<15 cc)?

PURPOSE: We evaluated the treatment outcomes of different prostate volumes (PVs), <15 cc, 15-20 cc, and > 20 cc, in patients with prostate cancer who underwent permanent seed implantation (PI) ± external beam radiation therapy ± hormone therapy in a national Japanese prospective cohort study (J-POPS). METHODS AND MATERIALS: Of the 6721 patients in J-POPS from 2005 to 2011, 6652 were included in the analysis population. We categorized the patients into the following three PV groups: <15 cc, 15-20 cc, and > 20 cc. We evaluated the effect of PV on biochemical freedom from failure (bFFF), prostate cancer-specific mortality (PCSM), and all-cause mortality (ACM) using the Phoenix definition and Cox proportional hazard models. RESULTS: The median follow-up period was 60.0 months. Patients in each PV group was 491 (7.4%), 1118 (16.8%), and 5043 (75.8%), respectively. No difference was observed in bFFF (94.7%, 96.2%, and 95.7%, p = 0.407), PCSM (99.8%, 99.7%, and 99.8%, p = 0.682), and ACM (98.2%, 96.7%, and 97.2%, p = 0.119) at 5 years for each PV group. In univariate and multivariate analyses, PV was not associated with bFFF, PCSM, ACM, or grade 2 toxicity. The percentage of positive biopsies was the single most significant predictor for all treatment outcomes. CONCLUSIONS: Our results obtained by analyzing a very large Japanese prospective database showed no difference in treatment outcomes according to PV (<15 cc, 15-20 cc, and ˃20 cc). Our study confirmed that PI in small prostates (even < 15 cc) remains an effective treatment option.

Effect of Functional Electrical Stimulation in Convalescent Stroke Patients: A Multicenter, Randomized Controlled Trial.

BACKGROUND: We evaluated whether the Walkaide® device could effectively improve walking ability and lower extremity function in post-stroke patients with foot drop. Patients aged 20-85 years with an initial stroke within ≤6 months and a functional ambulation classification score of 3 or 4 were eligible. MATERIALS AND METHODS: Patients were randomly allocated to the functional electrical stimulation (FES) or control group at a 1:1 ratio. A 40 min training program using Walkaide was additionally performed by the FES group five times per week for 8 weeks. The control group received the 40 min training program without FES. RESULTS: A total of 203 patients were allocated to the FES (n = 102) or control (n = 101) groups. Patients who did not receive the intervention or whose data were unavailable were excluded. Finally, the primary outcome data of 184 patients (n = 92 in each group) were analyzed. The mean change in the maximum distance during the 6-MWT (primary outcome) was 68.37 ± 62.42 m and 57.50 ± 68.17 m in the FES and control groups (difference: 10.86 m; 95% confidence interval: -8.26 to 29.98, p = 0.26), respectively. CONCLUSIONS: In Japanese post-stroke patients with foot drop, FES did not significantly improve the 6 min walk distance during the convalescent phase. The trial was registered at UMIN000020604.

Risk Factors of Dementia in Patients with Cerebral Vascular Diseases Based on Taiwan National Health Insurance Data.

INTRODUCTION: Vascular factors have been shown to be associated with increased risk of dementia. However, clinical trials have so far been unsuccessful, suggesting new approaches are needed. The aim of this study was to use population-based real-world data to investigate risk factors and preventive factors for dementia, including the effects of traditional Chinese medicine (TCM). METHODS: This is a retrospective cohort study using LHID2000, a dataset randomly selected from Taiwan's National Health Insurance Research Database. Subjects with occlusion and stenosis of precerebral and cerebral arteries, cerebral atherosclerosis without mention of cerebral infarction, and transient cerebral ischemia were included. Subjects with dementia at baseline were excluded. The primary endpoint was dementia. Data for demographic and clinical comorbid status and treatments administered at baseline in 2000 and at the end of follow-up in 2013 were included. RESULTS: A total of 4,207 subjects with cerebral vascular disease and no cognitive impairment were included, of whom 392 converted to dementia during an average 5.15-year (SD: 3.79) follow-up. Depression (adjusted HR: 1.54, 95% confidence interval [CI]: 1.13-2.09), osteoporosis (adjusted HR: 1.34, 95% CI: 1.04-1.74), and the use of enalapril (adjusted HR: 1.37, 95% CI: 1.09-1.73) were risk factors for dementia, while nitroglycerin (adjusted HR: 0.67, 95% CI: 0.53-0.85) was a protecting factor, in subjects with cerebrovascular diseases without mention of cerebral infarction. In total, statins were shown to be associated with decreased risk of dementia (HR: 0.73, 95% CI: 0.59-0.91); however, no one statin subtype or TCM had such an effect. CONCLUSION: Depression, osteoporosis, and the use of enalapril were associated with a higher risk of dementia, while nitroglycerin might be a protecting factor for dementia, in subjects with cerebrovascular diseases without mention of cerebral infarction.

Biochemical outcomes and toxicities in young men with prostate cancer after permanent iodine-125 seed implantation: Prospective cohort study in 6662 patients.

PURPOSE: We evaluated the effect of age, <60 and ≥60 years, on biochemical outcomes and toxicities in patients with prostate cancer who underwent permanent seed implantation (PI) ± external beam radiation therapy ± hormone therapy in a national Japanese prospective cohort study (J-POPS). METHODS AND MATERIALS: The safety and efficacy analyses included 6721 and 6662 patients, respectively. We categorized patients into two age groups: <60 (n = 716) and ≥60 (n = 6,005) years. We used propensity score matching (PSM) to estimate the marginal effect of age on biochemical freedom from failure (bFFF) using a Phoenix definition and Cox proportional hazard models. RESULTS: The median followup period was 60.0 months. Without PSM, men <60 years demonstrated similar 5-year bFFF (96.3%) compared with men ≥60 years (95.6%; p = 0.576); percent positive biopsies, biologically effective dose, Gleason score, risk classification, and supplemental external beam radiation therapy (p <0.001, <0.001, <0.001, 0.008, and <0.001) were significantly associated with bFFF while age was not (p = 0.576). With PSM, bFFF was not significantly different between age groups (p = 0.664); however, men <60 years showed a significantly lower incidence of declining erectile function, grade ≥2 all urinary toxicities, urinary frequency/urgency, and rectal bleeding (p <0.001, 0.024, 0.031, and 0.010) than men ≥60 years. CONCLUSIONS: After PI, men <60 years achieved a comparable 5-year biochemical control rate and showed a lower incidence of several toxicities compared to men ≥60 years. This suggests that PI should be an excellent treatment option for men <60 years with prostate cancer.

Combination bezafibrate and nivolumab treatment of patients with advanced non-small cell lung cancer.

Despite the success of cancer immunotherapies such as programmed cell death-1 (PD-1) and PD-1 ligand 1 (PD-L1) inhibitors, patients often develop resistance. New combination therapies with PD-1/PD-L1 inhibitors are needed to overcome this issue. Bezafibrate, a ligand of peroxisome proliferator-activated receptor-γ coactivator 1α/peroxisome proliferator-activated receptor complexes, has shown a synergistic antitumor effect with PD-1 blockade in mice that is mediated by activation of mitochondria in T cells. We have therefore now performed a phase 1 trial (UMIN000017854) of bezafibrate with nivolumab in previously treated patients with advanced non-small cell lung cancer. The primary end point was the percentage of patients who experience dose-limiting toxicity, and this combination regimen was found to be well tolerated. Preplanned comprehensive analysis of plasma metabolites and gene expression in peripheral cytotoxic T cells indicated that bezafibrate promoted T cell function through up-regulation of mitochondrial metabolism including fatty acid oxidation and may thereby have prolonged the duration of response. This combination strategy targeting T cell metabolism thus has the potential to maintain antitumor activity of immune checkpoint inhibitors and warrants further validation.

Implication of using cognitive function-related simple questions to stratify the risk of long-term care need: population-based prospective study in Kobe, Japan.

BACKGROUND: This study investigated how cognitive function-related simple questions can be used to identify older individuals who are at risk of needing long-term care. METHODS: This cohort study was conducted in Kobe city, Japan. In 2015, the municipal office distributed the Kihon Checklist by post, a 25-item questionnaire including three cognitive function-related questions (questions 18, 19, 20) to citizens aged ≥ 70 years. Need certification is routinely done by Kobe city as part of the national Long-Term Care Insurance Act. The answers to the 2015 questionnaire were merged with need certification data between the questionnaire delivery and the end of December 2019. RESULTS: Of the 77,877 citizens (age: 72.9 ± 2.7 years) who received the questionnaire, 50,154 responded (response rate: 64.4%). During the study period, the cumulative incidence of the need for long-term care was higher in those who did not respond than in those who did (12.5% vs 8.4%; P < 0.001). Among those who responded, the incidence of the need for long-term care was progressively greater as the number of negative answers to cognitive function-related questions increased (5.0%, 8.4%, 15.7% and 30.2% at 4 years' follow-up, for respondents with, respectively, 0, 1, 2 and 3 negative answers). Similarly, when the need certification for long-term care was confined to that accompanied by dementia, the incidence also rose as the number of negative responses to the cognitive function-related questions increased (3.4%, 6.5%, 13.7% and 27.9% for respondents with, respectively, 0, 1, 2 and 3 negative answers). Using multivariate Cox regression analysis, all three cognitive function-related questions were predictive of the need for long-term care, and question 18 (about memory loss) had the highest hazard ratio for predicting the need for long-term care accompanied by dementia. CONCLUSIONS: Use of cognitive function-related simple questions may help identify older adults at risk for needing long-term care, suggesting their potential value for use in administrative and policy approaches aimed at reducing the societal burden of dementia.

Enzalutamide in patients with non-metastatic castration-resistant prostate cancer after combined androgen blockade for recurrence following radical treatment in Japan (Japanese research for patients with non-metastatic castration-resistant prostate cancer-enzalutamide: JCASTRE-zero)-a prospective single-arm interventional study.

BACKGROUND: The effect of enzalutamide in patients with non-metastatic castration-resistant prostate cancer after combined androgen blockade, which represents a patient profile similar to real-world clinical practice in Japan, remains unknown. Therefore, we investigate the efficacy and safety of enzalutamide after combined androgen blockade for recurrence following radical treatment in Japanese patients with non-metastatic castration-resistant prostate cancer. METHODS: We analyzed 66 patients with non-metastatic castration-resistant prostate cancer after combined androgen blockade for recurrence following radical prostatectomy or radiation therapy who were prospectively enrolled from October 2015 to March 2018. They received enzalutamide 160 mg orally once daily until the protocol treatment discontinuation criteria were met. The primary endpoint was prostate-specific antigen-progression-free survival, defined as the time from enrollment to prostate-specific antigen-based progression or death from any cause. The secondary endpoints included overall survival, progression-free survival, metastasis-free survival, time to prostate-specific antigen progression, prostate-specific antigen response rate, chemotherapy-free survival, and safety assessment. RESULTS: The median observation period was 27.3 months. The median prostate-specific antigen-progression-free survival was 35.0 months (95% confidence interval, 17.5 to not reached). The median overall survival, median progression-free survival, median metastasis-free survival, and chemotherapy-free survival were not reached, with the corresponding 2-year rates being 91.6%, 67.1%, 72.4%, and 85.8%, respectively. The 50% prostate-specific antigen response rate was 88.9%, with the median time being 2.8 months. In total, 42.2% of the patients experienced adverse events, with malaise being the most common. CONCLUSIONS: Enzalutamide effectively manages non-metastatic castration-resistant prostate cancer after combined androgen blockade for recurrence following radical treatment. TRIAL REGISTRATION:  UMIN000018964, CRB6180007.

Phase II study of the efficacy and safety of lenvatinib for anaplastic thyroid cancer (HOPE).

PURPOSE: Anaplastic thyroid cancer (ATC) is a rare and highly aggressive cancer for which effective systemic therapy has long been sought. Here, we assessed the efficacy and safety of lenvatinib in patients with unresectable ATC. PATIENTS AND METHODS: The study was investigator-initiated and conducted under a multicenter, open-label, nonrandomized, phase II design. Eligibility criteria included pathologically proven ATC; unresectable measurable lesion as defined by RECIST 1.1; age 20 years or older; ECOG PS 0-2; and adequate organ function. The primary end-point was overall survival. Secondary end-points were progression-free survival, objective response rate, disease control rate, clinical benefit rate, and safety. RESULTS: Of 52 patients enrolled from 17 institutions, 42 patients who were confirmed to have ATC were included for efficacy analysis, and 50 patients were included for safety analysis. The estimated 1-year overall survival rate was 11.9% (95% CI, 4.4%-23.6%). One patient (2.4%) achieved complete response, four patients (9.5%) partial response, and 26 patients (61.9%) stable disease, including nine patients (21.4%) who demonstrated durable stable disease, giving an objective response rate of 11.9%, disease control rate of 73.8%, and clinical benefit rate of 33.3%. Adverse events of any grade were observed in 45 patients (90.0%), the most common of which of any grade included loss of appetite (48.0%), fatigue (48.0%), hypertension (44.0%), and palmar-plantar erythrodysesthesia syndrome (26.0%). CONCLUSION: Lenvatinib treatment resulted in disappointing survival for unresectable ATC patients. Although the number of responders was small, responses were durable, indicating that lenvatinib may be beneficial for selected patients. Further investigation to identify suitable candidates for lenvatinib monotherapy is needed.

Nationwide registry for patients with neuroendocrine neoplasm of pancreas, gastrointestinal tract, lungs, bronchi, or thymus in Japan.

BACKGROUND: Neuroendocrine neoplasm (NEN) is a comparatively rare tumor that has been considered indolent. Due to these characteristics, detailed epidemiological data have not been analyzed in Japan. To elucidate the present status of NEN diagnosis and treatment in Japan, we started a registry cohort study in January 2015. METHODS: Patients pathologically diagnosed with NENs of the pancreas, gastrointestinal tract, lungs, bronchi, or thymus after January 2012 were enrolled in this registry after the date of ethics review committee approval in each hospital or institute. Follow-up was continued for enrolled patients. RESULTS: During 5 years of enrollment between January 2015 and December 2019, a total of 1526 participants from 63 departments were enrolled in this registry (mean, 305.2 participants/year), covering approximately 5.8% of the annual incidence of NENs in Japan. For pancreatic NEN, 41.9% of patients had metastasis and the dominant metastatic site was the liver, at twice the rate of lymph node metastasis in the current registry. In contrast, the frequency of lymph node metastasis from gastrointestinal (GI)-NEN was similar to that of the liver. The distribution of WHO 2019-based grades varied according to the primary site. Low-to-intermediate grade (G1-G2) was dominant for duodenal, jejunal/ileal, rectal, and pancreatic NENs, whereas high grade (G3 or NEC) was dominant for esophageal, stomach, and colon NENs. For PanNENs, G3 and NEC accounted only for 1.6% and 2.9%, respectively. CONCLUSIONS: These cohort data provide crucial information for clinical research to clarify the characteristics of NENs in Japan.

Kobe project for the exploration of newer strategies to reduce the social burden of dementia: a study protocol of cohort and intervention studies.

INTRODUCTION: This research project addresses the lack of screening tools for the early detection of high-risk individuals for long-term care, through four individual studies.Study 1 investigates the predictive ability of the 'Kihon Check List', study 2 the 'Cognitive Function instrument' and EuroQol-5 Dimension (EQ-5D) and study 3 the 'Cognitive Function instrument' and EQ-5D as well as the 'Frail Kenshin' health check-up, for incident long-term care certification over a follow-up period of up to 4 years. This is the first large prospective study to evaluate the predictive ability of these tools for the outcome measure long-term care certification. The last subsection of this project study four aims to explore a mixed methods intervention for delaying the need for long-term care. This section is purely exploratory, looking for clues for further studies. METHODS AND ANALYSIS: Baseline data have been collected through local government programs, as well as through postal self-reported questionnaires. The primary outcome variable for all studies is long-term care certification data. Statistical analysis will be carried out using Kaplan-Meier, Multiple Cox regression as well as logistic regression. CONCLUSION: This project hopes to identify tools effective in predicting long-term care need. This will enable identification of citizens that are of higher risk for long-term care in the near future. This subset of high-risk individuals can in the future be addressed for extra support/intervention. ETHICS AND DISSEMINATION: All studies have been approved by respective institutional ethical committees and the WHO ethical committee ERC.0002899. In addition, all studies conform to the provisions of the Declaration of Helsinki and are conducted in accordance with Japan's 'Ethical Guidelines for Medical and Health Research Involving Human Subjects'. All findings will be disseminated at conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: UMIN000023283.

COVID-19 pathogenesis, prognostic factors, and treatment strategy: Urgent recommendations.

The pandemic of novel coronavirus disease (COVID-19) is not yet close to being over, more than 8 months after the first cases, but researchers are making great progress in fighting the disease. We have conducted a brief review of the geographic differences in the prevalence of COVID-19, the updated pathological findings, prognostic factors, and treatments for disease prevention and improvement of prognosis. Although hydroxychloroquine and tocilizumab have been recommended by some researchers, many clinical trials have failed to confirm any beneficial effect of these and other drugs on COVID-19, in terms of improved clinical status or reduced patient mortality. Currently, glucocorticoid is the only drug that reduces the mortality of COVID-19 in a randomized controlled trial; however, it is still necessary to establish the optimal timing of administration. It is also urgent to set up an international or national cohort to address the risk factors associated with infection, the natural history of COVID-19, including the disease type, surrogate markers for critically ill, long-term sequelae, and reinfection after exposure, identify responders to glucocorticoid, and establish optimal treatment strategies for disease control.

Protective Factors Modulate the Risk of Beta Amyloid in Alzheimer's Disease.

AIM: To identify the factors protecting Abeta-positive subjects with normal cognition (NC) or mild cognitive impairment (MCI) from conversion to Alzheimer's disease (AD). METHODS: Subjects with MCI in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, with baseline data for neuropsychological tests, brain beta amyloid (Abeta), magnetic resonance imaging (MRI), APOE genotyping, and 18F-FDG-PET (FDG), were included for analysis. RESULTS: Elevated brain amyloid was associated with a higher risk of conversion from MCI to AD (41.5%) relative to Abeta levels of <1.231 (5.5%) but was not associated with conversion from NC to AD (0.0 vs. 1.4%). In the multivariate Cox regression analyses, elevated Abeta increased the risk of AD, while higher whole-brain cerebral glucose metabolism (CGM) assessed by FDG decreased the risk of AD in subjects with the same amount of Abeta. Even in the patients with heavily elevated brain amyloid, those with FDG > 5.946 had a lower risk of AD. ApoE4 carrier status did not influence the protective effect. CONCLUSION: Higher average CGM based on FDG modified the progression to AD, indicating a protective function. The results suggest that the inclusion of this CGM measured by FDG would enrich clinical trial design and that increasing CGM along with the use of anti-Abeta agents might be a potential prevention strategy for AD.

Ten-year prospective evaluation of whole-body cancer screening with multiple modalities including [18F]fluorodeoxyglucose positron emission tomography in a healthy population.

PURPOSE: To prospectively evaluate the value of whole-body cancer screening with multiple modalities including FDG-PET in a healthy population. METHODS: The study was conducted in 1197 healthy individuals aged ≥ 35 years at enrollment between August 2003 and July 2004. All participants were scheduled to receive annual whole-body cancer screening five times (screening period) with subsequent long-term follow-up (follow-up period). The endpoints of the study were definitive cancer diagnosis, cancer-related death, and all-cause death. RESULTS: The follow-up rate was 99.8% for the screening period and 96.2% for the follow-up period. Forty-five cancers were confirmed during the screening period (August 2003 to July 2009), and 37 of the 45 were detected by the screening. Fourteen of the 45 were PET positive. Sixteen, 5, 4, 9 and 11 cancers were confirmed after the first, the second, the third, the fourth, and the fifth (took 2 years) screening, respectively. Eight participants died, of whom five died of cancer. The rate of cancer incidence (per 100,000) of 628.7 (95% confidence interval [CI] 445.0-812.4) was significantly high, and the rates of cancer mortality and all-cause mortality of 69.9 (95% CI 8.6-131.1) and 111.8 (95% CI 34.3-189.2), respectively, were significantly low, compared with the corresponding rates of 379.3, 138.2 and 354.2, respectively, in the age-rank- and sex-matched general population. During the follow-up period (August 2009 to July 2013), 37 cancers were confirmed and 30 of the 37 were detected. Seven participants died, of whom three died of cancer. The rate of cancer incidence was 809.6 (95% CI 548.7-1070.5). The rates of cancer mortality and all-cause mortality of 65.6 (95% CI 0-139.9) and 153.2 (95% CI 39.7-266.6), respectively, were significantly low compared with 190.1 and 462.3, respectively, in the general population. CONCLUSION: Cancer detection by PET alone was limited. While the high cancer incidence was attributed to the extensive screening, the low cancer and all-cause mortality may indicate the potential value of this type of cancer screening. Cancer incidence increases with aging and it has been shown that continuous screening may reduce the risk caused by the cancer progression.

Patient-reported health-related quality of life up to three years after the treatment with permanent brachytherapy: Outcome of the large-scale, prospective longitudinal study in Japanese-Prostate Cancer Outcome Study by Permanent I-125 Seed Implantation (J-POPS).

PURPOSE: To evaluate long-term health-related quality of life (HRQOL) impact of I-125 permanent seed implantation (PI) in Japanese patients with localized prostate cancer. MATERIALS AND METHODS: This is a longitudinal, prospective study of 2353 patients who enrolled in the nationwide Japanese-Prostate Cancer Outcome Study by Permanent I-125 Seed Implantation (J-POPS) from July 2005 to June 2007. HRQOL was measured before and after treatment (3, 12, 24, and 36 months) using the Medical Outcomes Study 8-items Short-Form Health Survey (SF-8) and the Expanded Prostate Cancer Index Composite Japanese version questionnaire. RESULTS: Of the total of 1511 patients who returned anonymized HRQOL questionnaires to Translational Research Center for Medical Innovation, 1079 underwent PI alone (PI group) and 432 underwent combined PI and external beam radiation therapy (EBRT) treatment (EBRT combination therapy group). The mental component summary score of SF-8 was improved at 12, 24, and 36 months compared with the pretreatment level. Although the urinary summary score at 3 months in the PI group was significantly lower than that in the EBRT combination therapy group, which recovered thereafter and was comparable to the score of the EBRT combination therapy group. The bowel summary score in the PI group was significantly higher than that in the EBRT combination therapy group at 12, 24, and 36 months. CONCLUSION: This longitudinal, large-scale prospective study indicated that the general HRQOL for PI was almost maintained 3 years after treatment. These results provide important information for patients with localized prostate cancer, who may select to receive I-125 brachytherapy.

Assessing long-term care risk in older individuals with possible cognitive decline: A large population-based study using the Kihon Checklist.

AIM: The present population-based study investigated the predictive ability of the Kihon Checklist (a self-reported frailty questionnaire) and the cognitive domain therein for incident long-term care need certification. This is the first large population-based study to investigate an association between the Kihon Checklist and the outcome measure, long-term care need certification. METHODS: The study population consisted of community-dwelling citizens aged >65 years who responded to the Kihon Checklist in Kobe City. The Kihon Checklist is a simple 26-item questionnaire to identify frail citizens, including three items (Q18-20) on subjective cognitive function (the cognitive domain). RESULTS: A total of 182 099 citizens were included for statistical analysis. The overall incidence of long-term care need certification was 1.6%, 3.5% and 5.4% at 1, 2 and 3 years. Associations were found between the Kihon Checklist questions and long-term care need certification. Furthermore, each unfavorable answer on the cognitive domain was associated with the risk for long-term care need (HR 1.493 for Q18, 1.285 for Q19, 1.321 for Q20, all P < 0.0001), independent of age, sex and other items on the Kihon Checklist. Also, after 3 years, as the number of unfavorable answers to the cognitive domain increased from 0 to 1, 2 and 3, the incidence of long-term care need certification progressively increased from 3.5% to 6.4%, 12.6% and 29.6%. CONCLUSIONS: The Kihon Checklist, especially the cognitive domain therein, appears to be predictive of long-term care need in community-dwelling citizens, suggesting the potential utility of the questionnaire for early detection of high-risk individuals. Geriatr Gerontol Int 2019; 19: 598-603.

Genitourinary toxicity after permanent iodine-125 seed implantation: The nationwide Japanese prostate cancer outcome study of permanent iodine-125 seed implantation (J-POPS).

PURPOSE: The purpose of this study was to evaluate acute and late genitourinary (GU) toxicity and to elucidate factors associated with GU toxicity in patients with prostate cancer treated with permanent seed implantation (PI) enrolled in a nationwide prospective cohort study in Japan. METHODS AND MATERIALS: Of 2,354 patients enrolled in this study, GU toxicity was evaluated in 2,339 patients at 3, 12, 24, and 36 months after PI. To elucidate independent factors predictive of acute and late Common Terminology Criteria for Adverse Events Grade 2 or higher (Grade ≥2) GU toxicity, multivariate logistic regression analyses were carried out. Regarding acute urinary retention (AUR), the incidence rate and the recovery rate for AUR were estimated using the Kaplan-Meier curve. RESULTS: Approximately 53% of the patients treated with PI alone and 42% of those treated with combination therapy with PI therapy and external beam radiation therapy showed urinary frequency/urgency at 3 months. The multivariate analysis revealed that age, prostate volume, pretreatment international prostate symptom score, drinking status, and PI were independent predictors of acute GU toxicity Grade ≥2. Of all patients, 53 (2.3%) suffered from AUR, and 49 (92.5%) recovered from AUR with a median time of 4.3 months during the followup period. CONCLUSIONS: The results of GU toxicity in Japanese patients who underwent low-dose-rate brachytherapy were acceptable and comparable to those previously reported in U.S. PATIENTS: The patients treated with PI alone showed a significantly higher incidence rate of GU toxicity than did those undergoing combination therapy with PI and external beam radiation therapy in the acute phase.

Development of a novel convenient Alzheimer's disease assessment scale, the ABC Dementia Scale, using item response theory.

AIM: The present study aimed to assess the interrater reliability and construct the validity of a novel, convenient informant-based Alzheimer's disease assessment scale to prepare its final version. METHODS: For the assessment, site investigators, co-medicals and, if available, medical staff other than doctors or co-medicals interviewed study informants to assess individuals using this scale. We then analyzed the interrater reliability and construct validity using factor analysis and item response characteristics. RESULTS: In this study, 427 eligible participants were enrolled. We first examined the interrater reliability, and found that the lower limit of the confidence interval of each item was never <0.4 (except for the item "delusion of theft"). After deleting this item, the 14 items of this scale were organized into three domains (activities of daily living, behavioral and psychological symptoms of dementia, and cognitive function) through factor analysis. After discussion of the similarity of two items and their integration into one item, we confirmed that the final version of the 13-item scale showed almost the same degree of interrater reliability and construct validity as the former version of this scale. CONCLUSIONS: The final version of this novel Alzheimer's disease assessment scale had high interrater reliability and construct validity. We named it the ABC (activities of daily living, behavioral and psychological symptoms of dementia, and cognitive function) Dementia Scale. Further studies on its validation are required. Geriatr Gerontol Int 2019; 19: 18-23.