Validation of a drug-based score in advanced urothelial carcinoma treated with pembrolizumab.

Aim: To validate a 'drug score' that stratifies patients receiving immunotherapy based on concomitant medications (antibiotics/proton pump inhibitors/corticosteroids) in urothelial carcinoma (UC). Materials & methods: We assessed oncological outcomes according to the drug score in 242 patients with advanced UC treated with pembrolizumab. Results: The drug score classified patients into three risk groups with significantly different survivals. Heterogeneous treatment effect analyses showed that the primary cancer site (bladder UC [BUC] or upper-tract UC [UTUC]) significantly affected the prognostic capability of the drug score; it significantly correlated with survivals in BUC, while there were no such correlations in UTUC. Conclusion: A drug score was examined in advanced UC treated with pembrolizumab and was validated in BUC but not in UTUC.

Drug treatment for cancer may be weakened by other drugs. We checked whether some kinds of drugs really weakened the effect of drug treatment for cancer. We found that it was true for some kinds of cancer but not for other kinds.

Recent advances in the molecular understanding of medulloblastoma.

Medulloblastoma is the most common pediatric malignant brain tumor composed of four molecular subgroups. Recent intensive genomics has greatly contributed to our understanding of medulloblastoma pathogenesis. Sequencing studies identified novel mutations involved in the cyclic AMP-dependent pathway or RNA processing in the Sonic Hedgehog (SHH) subgroup, and core-binding factor subunit alpha (CBFA) complex in the group 4 subgroup. Likewise, single-cell sequencing provided detailed insights into the cell of origin associated with brain development. In this review, we will summarize recent findings by sequencing analyses for medulloblastoma.

Improved survival in real-world patients with advanced urothelial carcinoma: A multicenter propensity score-matched cohort study comparing a period before the introduction of pembrolizumab (2003-2011) and a more recent period (2016-2020).

OBJECTIVES: Although the treatment strategy for advanced urothelial carcinoma (aUC) has drastically changed since pembrolizumab was introduced in 2017, studies revealing current survival rates in aUC are lacking. This study aimed to assess (1) the improvement in survival among real-world patients with aUC after the introduction of pembrolizumab and (2) the direct survival-prolonging effect of pembrolizumab. METHODS: This multicenter retrospective study included 531 patients with aUC undergoing salvage chemotherapy, including 200 patients treated in the pre-pembrolizumab era (2003-2011; earlier era) and 331 patients treated in a recent 5-year period (2016-2020; recent era). Using propensity score matching (PSM), cancer-specific survival (CSS) and overall survival (OS) were compared between the earlier and recent eras, in addition to between the recent era, both with and without pembrolizumab use, and the earlier era. RESULTS: After PSM, the recent era cohort had significantly longer CSS (21 months) and OS (19 months) than the earlier era cohort (CSS and OS: 12 months). In secondary analyses using PSM, patients treated with pembrolizumab had significantly longer CSS (25 months) and OS (24 months) than those in the earlier era cohort (CSS and OS: 11 months), whereas patients who did not receive pembrolizumab in the recent era had similar outcomes (CSS and OS: 14 months) as the earlier era cohort (CSS and OS: 12 months). CONCLUSIONS: Patients with aUC treated in the recent era exhibited significantly longer survival than those treated before the introduction of pembrolizumab. The improved survival was primarily attributable to the use of pembrolizumab.

[Changes in homebound status and related factors in community-dwelling older adults participating in physical checkups over two years].

Objective　This study aims to identify changes in homebound status and related factors in community-dwelling older adults participating in physical checkups over two years in order to help with prevention and recovery from being homebound.Methods　A survey on needs in the sphere of daily life was conducted in July 2011 among 6,696 independent older adults in 10 regions of Kameoka City (baseline survey). Of the 6,696 adults, 1,379 responded to the survey and participated in a physical checkup held between March and April 2012. These individuals were then invited to a similar checkup again in September 2013. Of these, 638 consenting individuals were administered a questionnaire survey (follow-up survey). In all, 522 subjects responded to both surveys (baseline and follow-up) regarding being homebound. The responses involved basic attributes, state of daily living, state of health, items of the Kihon Checklist, items concerning daily living activities in the baseline survey, and items concerning being homebound in the follow-up survey. The responses were analyzed, and an evaluation of homebound status was conducted based on whether or not one (or both) of the two items of the Kihon Checklist were applicable. The subjects were classified according to the following: 1) whether non-homebound individuals remained non-homebound (non-homebound group) or whether they became homebound (homebound transition group) and 2) whether individuals who became homebound recovered (recovery group) or remained the same (persisting group). After comparing the characteristics of each group, a logistic regression analysis was employed to analyze the factors related to changes in homebound status after two years.Results　Of the 375 non-homebound individuals in the baseline survey, 326 (86.9%) and 49 (13.1%) were classified into non-homebound and homebound transition groups, respectively. Of the 147 subjects who became homebound, 85 (57.8%) and 62 (42.2%) were classified into the recovery and persisting groups, respectively.　Among the factors related to change in homebound status after two years, a low score of social role (OR=0.675, CI=0.458-0.997) was an independent factor for being at risk of becoming homebound (P<0.05). Having no diseases under treatment (OR=14.340, CI=1.345-152.944) and a high intellectual activity score (OR=2.643, CI=1.378-5.069) were independent factors of recovery from being homebound (P<0.05).Conclusion　The results of the two year longitudinal study suggest the need for support for non-homebound older individuals devoid of social roles to prevent homebound status. Additionally, there is a need for support surrounding the reduction in obtaining a disease and maintaining intellectual activity in order to recover from being homebound.

A Dementia Café as a Bridgehead for Community-Inclusive Care: Qualitative Analysis of Observations by On-the-Job Training Participants in a Dementia Café.

BACKGROUND/AIMS: Dementia cafés are becoming widespread as a new approach to dementia care, but their operational procedures and significance have not been adequately studied. METHODS: On-the-job training (OJT) for professionals planning to operate a dementia café in the future was conducted in a pioneering dementia café in Japan. The reports of OJT trainees' observations and learning were analyzed qualitatively. RESULTS: Reports could be summarized in up to 9 themes: 2 related to the atmosphere and significance of the café, 3 related to the guests, such as people with dementia and their families, and 4 related to the café staff. DISCUSSION: The results of the present study identified the elements that make up dementia cafés and their significance and suggest that dementia cafés could be a new type of community resource for dementia care in the future.

[Physical fitness and depression symptoms in community-dwelling elderly women].

OBJECTIVES: The aim of this study was to examine the relationship between geriatric depression scale (GDS) score and elements of physical fitness in community-dwelling, healthy, elderly women in Japan. METHODS: This cross-sectional study involved a total of 886 healthy elderly women (aged 265 years) living in Kyoto prefecture. Women voluntarily participated in physical performance tests. One-leg standing time, leg power, knee extension strength, grip strength, endurance capacity, trunk flexion, usual and maximal gait speed, chair stand, chair stepping, and functional reach were examined as fitness tests. A 15-item GDS and a battery of health status questionnaires were used to assess mental and physical health status. RESULTS: Of the participants, 21.1% had a GDS score of > or = 5 and were categorized as the depression group (D group). Leg power, knee extension strength, endurance capacity, gait speed, and chair stepping ability were significantly lower in the D group than in the non-depression group (GDS score < 5; ND group). After adjustment for physical characteristics, eating habits, and physical activity levels as co-variances, leg power, knee extension strength, and endurance capacity remained significantly lower in the D group than in the ND group (P < 0.05). CONCLUSION: A considerable number of active, healthy, elderly women who voluntarily participated in this study reported depressive symptoms. Reduced leg power, knee extension strength, and endurance capacity were associated with depressive symptoms independently of physical activity levels. These results suggest that exercise intervention to increase leg strength and endurance capacity may improve depressive symptoms in elderly women.

Both conventional indices of cognitive function and frailty predict levels of care required in a long-term care insurance program for memory clinic patients in Japan.

AIM: To delineate relationships among cognitive function, frailty and level of care required in the Japanese long-term care insurance program (LTCIP) in outpatient memory clinic patients. METHODS: This was a cross-sectional study carried out at an outpatient memory clinic. Participants were 201 cognitively impaired patients. Cognitive function was measured by the Mini-Mental State Examination (MMSE). Frailty was measured by Timed Up & Go (TUG) and grip strength. Waist circumference, body mass index, living arrangement and level of care required in the LTCIP (rank 1 minor disability to rank 7 severe disability) were also assessed. RESULTS: Mean age, MMSE score, TUG score and grip strength were 78.8 ± 6.9 years, 19.6 ± 6.1, 14.6 ± 6.7 s and 16.9 ± 7.5 kg, respectively. A total of 70 patients (34.8%) had not applied for the certification, at least in part because of their younger age and existence of family caregivers. LTCIP rank was correlated both with MMSE score (ß: -0.49, P = 0.001), grip strength (ß: -0.27, P = 0.005) and living alone (ß: -0.18, P = 0.03), but not with TUG score (ß: 0.14, P = 0.105). CONCLUSION: In outpatients of a memory clinic, care ranks, which define the upper limit of monthly benefit in the Japanese LTCIP, were influenced by age, cognitive function, frailty and living arrangements. Understanding the relationship among these parameters would be useful in predicting the needs of cognitively impaired patients and important when comparing the possible services provided by long-term care systems for them worldwide.

[Behavioral and psychological symptoms, cognitive impairment and caregiver burden related to Alzheimer's disease patients treated in an outpatient memory clinic].

AIM: The relationships among behavioral and psychological symptoms of dementia (BPSD), cognitive impairment of Alzheimer's disease (AD) patients and the caregiver burden of their caregivers were investigated in an outpatient memory clinic. METHODS: Forty-six pairs of AD patients and their family caregivers were involved in this study. Neuropsychiatry Inventory (NPI) was used to estimate BPSD, to which memory symptoms were added as a subcategory of BPSD. MMSE, word fluency, clock drawing test and category-cued memory test were used for cognitive measurement. Zarit burden interview (ZBI) and CES-D were used to assess caregiver burden. RESULTS: Among 11 BPSD subcategories, memory symptoms, apathy, depression, delusion, aggression and anxiety were prevalent BPSD was a strong determinant of caregiver burden. Among BPSD symptoms, anxiety, aggression and aberrant motor behavior were significantly related to ZBL In terms of the relationship between BPSD and cognitive impairment, the scores for delusion and apathy were significantly related to the cognitive decline. On the other hand, patients who showed symptoms related to memory and depression had higher cognitive function than those who did not. CONCLUSION: These analyses will contribute to better assessment of AD patients and their caregivers, hopefully resulting in better support for them.