A randomized phase III study evaluating dexamethasone-based mouthwash to prevent chemotherapy-induced stomatitis in patients with breast cancer.

Stomatitis, which is a common side effect of chemotherapy, currently lacks a standardized approach for its prevention. Therefore, this multicenter, randomized, open-label, controlled phase III trial aims to assess the efficacy and safety of a dexamethasone-based mouthwash for preventing chemotherapy-induced stomatitis in patients with early breast cancer. We will randomly assign 230 patients with early breast cancer scheduled to receive chemotherapy in a 1:1 ratio to either the dexamethasone-based mouthwash group (10 ml, 0.1 mg/ml; swish for 2 min and spit 4 times daily for 8 weeks) or the mouthwash-with-tap-water group. The incidence of stomatitis, measured using electronic patient-reported outcomes, is the primary endpoint.

The Sri Lanka Mother and Newborn Growth (S-MaNGro) Cohort: Protocol of a Nationwide Prospective Study.

Perinatal cohort studies with a prospective longitudinal design are critical for determining the effects of early-life exposures on offspring's health outcomes. The Sri Lanka Mother and Newborn Growth cohort study aims to investigate the impact of maternal nutritional and psychosocial factors on newborns' birth weight in the Sri Lankan context. This paper presents the methodology of participant recruitment, follow-ups, an overview of measurements, and planned data analyses. This study included a nationally representative sample of Sri Lankan pregnant women recruited in their first trimester of pregnancy. Follow-up assessments were conducted once during the second and third trimesters of pregnancy and after the baby's birth, prospectively tracking the women's dietary intake, mental health, hemoglobin concentrations, and gestational weight gain data. Once the participants delivered their babies, the data on gestational age, sex of the newborn, birth weight, length and occipitofrontal circumference at birth, and mode of delivery were collected. Between August 2022 and August 2023, we recruited 2000 first-trimester pregnant women to the cohort and continued to follow up with them until the baby's birth. The response rates were 90.4%, 81.4%, and 75.2% in the first, second, and third follow-ups. We plan to analyze the data in July 2024. We expect this study to provide valuable insights into various early-life exposures affecting neonatal birth weight. The study's findings will serve as a valuable information resource for a broader scientific community, enabling the development of effective policies to prevent low-birth-weight deliveries in low-resource settings.

A Dementia-Friendly Educational Program Using Virtual Reality for the General Public in Japan: A Randomized Controlled Trial for DRIVE.

BACKGROUND AND OBJECTIVES: Raising dementia awareness is essential for building a dementia-friendly community. However, existing studies have underexplored the effects of virtual reality (VR) dementia educational programs for the general public on enhancing positive attitude toward dementia. This study aimed to examine the effectiveness of a VR dementia-friendly educational program called the Drive for Dementia Readiness Inside Virtual Reality (DRIVE) program to improve attitude toward dementia of the general public. RESEARCH DESIGN AND METHODS: A two-arm randomized controlled trial was conducted. Eligibility criteria for participants included being 16 years and older in Japan and having no professional license in healthcare and social care. We randomized individuals to attend a multielement VR dementia-friendly educational program (intervention), including simulation, VR films, short films, lectures, and discussions or a lecture-based program (control). Data were collected 3 times, including at baseline, postintervention, and 3-month follow-up. The primary outcome was attitude toward dementia. The secondary outcomes were intention of helping behavior for people living with dementia and knowledge of dementia. RESULTS: We recruited 157 community residents, among whom 130 were included in the analysis. Although the mean changes in attitude score were not significantly different between the groups (Hedge's g = 0.26), the intention of helping behavior score was significantly higher in the intervention group (g = 0.49). DISCUSSION AND IMPLICATION: The DRIVE, a VR-based multielement dementia-friendly educational intervention, was shown as a promising tool for significantly affecting the intention of helping behavior for people living with dementia to establish dementia-friendly communities. CLINICAL TRIALS REGISTRATION NUMBER: UMIN000044901.

Association of longitudinal pet ownership with wheezing in 3-year-old children using the distributed lag model: the Japan Environment and Children's Study.

BACKGROUND: Time-varying exposures like pet ownership pose challenges for identifying critical windows due to multicollinearity when modeled simultaneously. The Distributed Lag Model (DLM) estimates critical windows for time-varying exposures, which are mainly continuous variables. However, applying complex functions such as high-order splines and nonlinear functions within DLMs may not be suitable for situations with limited time points or binary exposure, such as in questionnaire surveys. OBJECTIVES: (1) We examined the estimation performance of a simple DLM with fractional polynomial function for time-varying binary exposures through simulation experiments. (2) We evaluated the impact of pet ownership on childhood wheezing onset and estimate critical windows. METHODS: (1) We compared logistic regression including time-varying exposure in separate models, in one model simultaneously, and using DLM. For evaluation, we employed bias, empirical standard error (EmpSE), and mean squared error (MSE). (2) The Japan Environment and Children's Study (JECS) is a prospective birth cohort study of approximately 100,000 parent-child pairs, registered across Japan from 2011 to 2014. We applied DLM to the JECS data up to age 3. The estimated odds ratios (OR) were considered to be within critical windows when they were significant at the 5% level. RESULTS: (1) DLM and the separate model exhibited lower bias compared to the simultaneously model. Additionally, both DLM and the simultaneously model demonstrated lower EmpSEs than the separate model. In all scenarios, DLM had lower MSEs than the other methods. Specifically, where critical windows is clearly present and exposure correlation is high, DLM showed MSEs about 1/2 to 1/200 of those of other models. (2) Application of DLM to the JECS data showed that, unlike other models, a significant exposure effect was observed only between the ages of 0 and 6 months. During that periods, the highest ORs were 1.07 (95% confidence interval, 1.01 to 1.14) , observed between the ages of 2 and 5 months. CONCLUSIONS: (1) A simple DLM improves the accuracy of exposure effect and critical windows estimation. (2) 0-6 months may be the critical windows for the effect of pet ownership on the wheezing onset at 3 years.

Goodness-of-fit tests for modified Poisson regression possibly producing fitted values exceeding one in binary outcome analysis.

Modified Poisson regression, which estimates the regression parameters in the log-binomial regression model using the Poisson quasi-likelihood estimating equation and robust variance, is a useful tool for estimating the adjusted risk and prevalence ratio in binary outcome analysis. Although several goodness-of-fit tests have been developed for other binary regressions, few goodness-of-fit tests are available for modified Poisson regression. In this study, we proposed several goodness-of-fit tests for modified Poisson regression, including the modified Hosmer-Lemeshow test with empirical variance, Tsiatis test, normalized Pearson chi-square tests with binomial variance and Poisson variance, and normalized residual sum of squares test. The original Hosmer-Lemeshow test and normalized Pearson chi-square test with binomial variance are inappropriate for the modified Poisson regression, which can produce a fitted value exceeding 1 owing to the unconstrained parameter space. A simulation study revealed that the normalized residual sum of squares test performed well regarding the type I error probability and the power for a wrong link function. We applied the proposed goodness-of-fit tests to the analysis of cross-sectional data of patients with cancer. We recommend the normalized residual sum of squares test as a goodness-of-fit test in the modified Poisson regression.

Pilot trial of an electronic patient-reported outcome monitoring system in patients with metastatic breast cancer undergoing chemotherapy.

BACKGROUND: Electronic patient-reported outcomes monitoring (ePROM) is a useful communication tool for patients and healthcare providers in cancer chemotherapy. In this study, we examined the feasibility of our newly developed ePROM system, which we refer to as "Hibilog". METHODS: An ePROM app was developed by extracting 18 items from the Patient-Reported Outcome-Common Terminology Criteria for Adverse Events (PRO-CTCAE). Symptom monitoring was conducted every two weeks for patients with metastatic breast cancer undergoing chemotherapy. The primary outcome was the response rate to the ePROM system. The secondary outcomes were response time, item missing rate, and distribution of responses for each symptom. RESULTS: A total of 71 cases (mean age 52.6 years) were analyzed. Performance status was 0 in 76% of the cases and 1 or higher in 24%. First-line treatment was being administered in 30% of cases, second-line treatment in 17%, and third-line or higher treatment in 53%. The response rate to the ePROM system from registration to week 40 remained high at around 80%, indicating good compliance. The average response time was 5.5 min and the missing rate for each item was below 0.4%. Among 1,093 responses, the top 3 symptoms causing interference with daily life were Fatigue (63%), Numbness and tingling (48%), and General pain (46%). CONCLUSION: Our developed ePROM system was able to capture symptoms accurately in patients with metastatic breast cancer undergoing chemotherapy while maintaining a high response compliance.

A risk-based subgroup analysis of the effect of adjuvant S-1 in estrogen receptor-positive, HER2-negative early breast cancer.

PURPOSE: The Phase III POTENT trial demonstrated the efficacy of adding S-1 to adjuvant endocrine therapy for estrogen receptor-positive, HER2-negative early breast cancer. We investigated the efficacy of S-1 across different recurrence risk subgroups. METHODS: This was a post-hoc exploratory analysis of the POTENT trial. Patients in the endocrine-therapy-only arm were divided into three groups based on composite risk values calculated from multiple prognostic factors. The effects of S-1 were estimated using the Cox model in each risk group. The treatment effects of S-1 in patients meeting the eligibility criteria of the monarchE trial were also estimated. RESULTS: A total of 1,897 patients were divided into three groups: group 1 (≤ lower quartile of the composite values) (N = 677), group 2 (interquartile range) (N = 767), and group 3 (> upper quartile) (N = 453). The addition of S-1 to endocrine therapy resulted in 49% (HR: 0.51, 95% CI: 0.33-0.78) and 29% (HR: 0.71, 95% CI 0.49-1.02) reductions in invasive disease-free survival (iDFS) events in groups 2 and 3, respectively. We could not identify any benefit from the addition of S-1 in group 1. The addition of S-1 showed an improvement in iDFS in patients with one to three positive nodes meeting the monarchE cohort 1 criteria (N = 290) (HR: 0.47, 95% CI: 0.29-0.74). CONCLUSIONS: The benefit of adding adjuvant S-1 was particularly marked in group 2. Further investigations are warranted to explore the optimal usage of adjuvant S-1.

Real-world experience with 5-aminolevulinic acid for photodynamic diagnosis of bladder cancer (3rd report): Cost impact of transurethral resection of bladder tumor in Japan.

BACKGROUND: Photodynamic diagnosis-assisted transurethral resection of bladder tumor (PDD-TURBT) showed improvement of diagnostic accuracy and treatment efficacy compared to white light TURBT (WL-TURBT). While PDD-TURBT is highly effective, PDD-TURBT requires the use of PDD device and light-sensitive substance precursor, which increases the medical cost compared to WL-TURBT. In this study, the impact on health care economic costs were examined between PDD-TURBT and WL-TURBT. METHODS: Of the total 265 patients, 88 patients for WL-TURBT and 105 patients for PDD-TURBT were available for analysis. Costs were also examined between 34 patients without false-positives and 36 patients with false-positives with a follow-up period of at least 200 days. To compare costs between the two treatments, we calculated the cost/person/year of TURBT using Japanese Diagnosis Procedure Combination and Per-Diem Payment System (DPC/PDPS). RESULTS: The total number of surgeries including the first TURBT was 135 (47 recurrences) in the WL-TURBT group and 133 (28 recurrences) in the PDD-TURBT group. The cost per person for hospitalization and surgery was 366,310 Japanese yen (JPY) for the WL-TURBT and 501,930 JPY for the PDD-TURBT. The cost per person per year was 491,622 JPY in the WL-TURBT group and 506,405 JPY in the PDD-TURBT group. Regarding false-positives, the cost per person per year was 494,544 JPY in the group without false-positives and 328,086 JPY in the group with false-positives. CONCLUSIONS: Although PDD-TURBT is cost more than WL-TURBT for one surgical hospitalization, the cost per person per year for PDD-TURBT and WL-TURBT is cost-neutral.

Development and validation of a symptom illustration scale from the patient-reported outcome common terminology criteria for adverse events for patients with breast cancer.

PURPOSE: Emojis are commonly used for daily communication and may be useful in assessing patient-reported outcomes (PROs) in breast cancer. The purpose of this study is to develop and validate a Symptom Illustration Scale (SIS) as a new PRO measurement. METHODS: Eighteen original SIS items were developed from the PRO-CTCAE. In cohort one, the SIS validity and reliability were examined in patients with breast cancer, using a semi-structured five-question survey to investigate content validity. PROs with PRO-CTCAE and SIS were examined twice to determine criteria validity and test-retest reliability. In cohort two, the responsiveness of the scales were examined in patients treated with anthracycline, docetaxel, paclitaxel, and endocrine therapy. PROs with PRO-CTCAE and SIS were investigated two or three times, depending on the therapy. RESULTS: Patients were enrolled from August 2019 to October 2020. In cohort one (n = 70), most patients had no difficulties with the SIS, but 16 patients indicated that it was difficult to understand severities in the SIS. For criterion validity, Spearman rank correlation coefficients (rs) between PRO-CTCAE and SIS items were ≥ 0.41, except for "Decreased appetite." For test-retest reliability, κ coefficients of the SIS were ≥ 0.41 for 16/18 items (88.9%). Response time was significantly shorter for the SIS than for PRO-CTCAE (p < 0.001). In cohort two (n = 106), score changes between PRO-CTCAE and SIS for relevant symptoms all had correlations with rs ≥ 0.41. CONCLUSION: An original SIS from the PRO-CTCAE for patients with breast cancer were verified the validity, reliability, and responsiveness. Further studies to improve and validate the SIS are needed.

Using a Sample Size Calculation Framework for Clinical Prediction Models When Developing and Selecting Mapping Algorithms Based on Linear Regression.

PURPOSE: To propose using a framework for calculating the sample size for clinical prediction models when developing and selecting mapping algorithms from a health-related quality-of-life (HRQOL) measure onto the score of a preference-based measure (PBM) using linear regression. METHODS: The framework was summarized for health economics researchers. Mapping studies that mapped the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 onto the EQ-5D-3L index using linear regression were evaluated in terms of sample size. The required sample size for each study was calculated using 4 criteria: global shrinkage factor ≥ 0.9, difference between the apparent and adjusted R2 ≤ 0.05, multiplicative margin of error in the estimated residual standard deviation ≤ 1.1, and absolute margin of error in the estimated model intercept ≤ 0.025. RESULTS: Ten mapping studies were identified. The information required to calculate the sample size was successfully extracted from previous mapping studies. Four of 10 mapping studies did not have sufficient sample sizes. LIMITATIONS: Further extension of this framework to other regression approaches used in mapping studies is necessary. CONCLUSIONS: The sample size should be considered when developing and selecting a mapping algorithm based on linear regression. HIGHLIGHTS: No recommendation or guidance is available for the sample size to develop and select a mapping algorithm from a health-related quality-of-life measure onto the score of a preference-based measure.This research proposes using a framework for calculating the sample size for clinical prediction models in sample size consideration for mapping algorithms using linear regression.A survey showed that the information required to calculate the sample size could be successfully extracted from previous mapping studies and that 4 of 10 mapping studies did not have sufficient sample sizes.

Impacts of the preceding cancer-specific health-related quality of life instruments on the responses to the subsequent EQ-5D-5L.

BACKGROUND: In clinical studies, the EQ-5D-5L is often employed with disease-specific health-related quality of life instruments. The questions in the former are more general than the latter; however, it is known that responses to general questions can be influenced by preceding specific questions. Thus, the responses to the EQ-5D-5L have the possibility of being influenced by the preceding disease-specific health-related quality of life instruments. This may lead to bias in the cost-effectiveness analysis results. Therefore, this study aimed to evaluate the impact of the preceding cancer-specific health-related quality of life instruments on the EQ-5D-5L responses. METHODS: We prepared questionnaire booklets containing the EQ-5D-5L, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, and the Functional Assessment of Cancer Therapy General with different orders. Using a quasi-randomized design, they were distributed to the patients undergoing drug therapy for advanced cancer, who were classified into three groups: Groups 1, 2, and 3 (the EQ-5D-5L placed first, second, and last, respectively). We compared the EQ-5D-5L index and the missingness of EQ-5D-5L among the groups. RESULTS: The mean EQ-5D-5L index was 0.796, 0.760, and 0.789 for groups 1 (n = 300), 2 (n = 306), and 3 (n = 331), respectively. The difference between Groups 2 and 1 was - 0.036 (95% CI - 0.065 to - 0.007; p = 0.015). The proportion of patients with an incomplete EQ-5D-5L was 0.11, 0.11, and 0.05 for Groups 1, 2, and 3, respectively. The difference of the proportions between group 3 and 1 and between 3 and 2 was - 0.06 (95% CI - 0.10 to - 0.02; p = 0.003) and - 0.06 (95% CI - 0.10 to - 0.02; p = 0.003), respectively. CONCLUSIONS: Although the EQ-5D-5L index differed according to the instrument orders, the difference size would not be considerably larger than the minimally important difference. The patients tended to complete the EQ-5D-5L when they were placed at the end of the questionnaire.

Pet ownership-related differences in medical and long-term care costs among community-dwelling older Japanese.

This study examined the differences in medical and long-term care costs over 18 months between pet owners and non-owners among community-dwelling older Japanese. Pet ownership data were collected from 460 community-dwelling adults age 65 years and older. These data were matched with data from the National Health Insurance, health insurance for older people, and Long-Term Care Insurance beneficiaries for 17 months back from the survey on pet ownership. Pet-ownership group-specific trajectories in monthly medical and long-term care costs were modeled by a generalized estimating equation. Among pet owners (n = 96, 20.9%) and non-pet owners (n = 364, 79.1%) there were no significant differences in baseline demographic or health characteristics including chronic disease and self-reported long-term care level. At baseline, pet owners had estimated monthly medical costs of ¥48,054 (SE = 0.11; $418), compared to ¥42,260 (SE = 0.06; $367) for non-pet owners. The monthly medical costs did not differ significantly between the two groups during the 18-month follow-up period. At baseline, estimated monthly long-term care costs of pet owners and non-pet owners were ¥676 (SE = 0.75; $6) and ¥1,420 (SE = 0.52; $12), respectively. During the follow-up period, the non-pet owner to owner ratio of monthly long-term care costs was 1.2 at minimum and 2.3 at maximum. This study showed that monthly long-term care costs for pet owners were approximately half those of non-pet owners. Pet owners might use long-term care services less frequently, or use lighter care services.

Diagnostic ability using fatty liver and metabolic markers for metabolic-associated fatty liver disease stratified by metabolic/glycemic abnormalities.

AIMS/INTRODUCTION: Although several noninvasive predictive markers for fatty liver and metabolic markers have been used for fatty liver prediction, whether such markers can also predict metabolic-associated fatty liver disease (MAFLD) remains unclear. We aimed to examine the ability of existing fatty liver or metabolic markers to predict MAFLD. MATERIALS AND METHODS: Participants in a high-volume center in Tokyo were classified into groups with and without MAFLD, based on the presence of metabolic abnormalities and fatty liver diagnosed through abdominal ultrasonography, between 2008 and 2018. The diagnostic abilities of three fatty liver markers: fatty liver index (FLI), hepatic steatosis index (HSI), and lipid accumulation product (LAP), and three common metabolic markers: waist-to-height ratio (WHR), body mass index (BMI), and waist circumference (WC), for predicting MAFLD, were evaluated. Analyses stratified by MAFLD subtypes were performed. RESULTS: Of 92,374 individuals, 19,392 (36.1%) had MAFLD. The diagnostic performances for MAFLD prediction, measured as c-statistics, for FLI, HSI, LAP, WHR, BMI, and WC were 0.906, 0.892, 0.878, 0.844, 0.877, and 0.878, respectively. Optimal cutoff values for diagnosing MAFLD for FLI, HSI, LAP, WHR, BMI, and WC were 20.3, 32.7, 20.0, 0.49, 22.9, and 82.1, respectively. Analyses stratified by MAFLD subtypes, based on BMI and metabolic/glycemic abnormalities, suggested that FLI and HSI had acceptable (c-statistics >0.700) diagnostic abilities throughout all the analyses. CONCLUSIONS: All six markers were excellent predictors of MAFLD in diagnosing among the general population, with FLI and HSI particularly useful among all sub-populations.

A Randomized Control Trial for ReDeSign: A Dementia-Friendly Mobile Microlearning Training for Store Workers in Japan.

BACKGROUND AND OBJECTIVES: Dementia-friendly training should be incorporated in neighborhood stores for people living with dementia to maintain engagement in social activities. However, there is a lack of evidence of dementia-friendly training in these workplaces, and existing trainings have time constraints. We developed a mobile microlearning program based on stigma theory and the bystander intervention model. This study aimed to evaluate the microlearning program's effectiveness. RESEARCH DESIGN AND METHODS: Convenience store workers in Tokyo were recruited for a randomized, waiting-list, and controlled trial. The intervention group completed a 50-min online course. The primary outcome was an attitude toward people living with dementia. The secondary outcomes were knowledge of dementia and helping behavior toward customers suspected of having dementia. Data were collected at baseline, after 1 month, and 4 months following the randomization. RESULTS: Process evaluations confirmed satisfaction and high completion rates of the program. In total, 150 participants were included in the analysis. The intervention group showed significantly greater improvements in attitude (Hedge's g = 0.70) and knowledge (g = 0.59) after 1 month, compared to the control group. Helping behavior increased in the intervention group, although it did not differ significantly between the groups. All outcomes remained significantly improved after 4 months. DISCUSSION AND IMPLICATIONS: The findings provide evidence that dementia-friendly training reduces the general public's stigma and increases helping behavior in stores. Mitigation of time constraints through mobile microlearning is expected to contribute to the dissemination and help people living with dementia maintain their social participation in the communities. Clinical Trials Registration Number: UMIN000043623.

Gradient Boosted Tree Approaches for Mapping European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 Onto 5-Level Version of EQ-5D Index for Patients With Cancer.

OBJECTIVES: This study aimed to develop direct and response mapping algorithms from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 onto the 5-level version of EQ-5D index based on the gradient boosted tree (GBT), a promising modern machine learning method. METHODS: We used the Quality of Life Mapping Algorithm for Cancer study data (903 observations from 903 patients) for training GBTs and testing their predictive performance. In the Quality of Life Mapping Algorithm for Cancer study, patients with advanced solid tumor were enrolled, and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and 5-level version of EQ-5D were simultaneously evaluated. The Japanese value set was used for direct mapping, whereas the Japanese and US value sets were used for response mapping. We trained the GBTs in the training data set (80%) with cross-validation and tested the predictive performance measured by the root mean squared error (RMSE), mean absolute error (MAE), and mean error in the test data set (20%). RESULTS: The RMSE and MAE in the test data set were larger in the GBT approaches than in the previously developed regression-based approaches. The mean error in the test data set tended to be smaller in the GBT approaches than in the previously developed regression-based approaches. CONCLUSIONS: The predictive performances in the RMSE and MAE did not improve by the GBT approaches compared with regression approaches. The flexibility of the GBT approaches had the potential to reduce overprediction and underprediction in poor and good health, respectively. Further research is needed to establish the role of machine learning methods in mapping a nonpreference-based measure onto health utility.

Simultaneous relaxometry and morphometry of human brain structures with 3D magnetic resonance fingerprinting: a multicenter, multiplatform, multifield-strength study.

Relaxation times and morphological information are fundamental magnetic resonance imaging-derived metrics of the human brain that reflect the status of the underlying tissue. Magnetic resonance fingerprinting (MRF) enables simultaneous acquisition of T1 and T2 maps inherently aligned to the anatomy, allowing whole-brain relaxometry and morphometry in a single scan. In this study, we revealed the feasibility of 3D MRF for simultaneous brain structure-wise morphometry and relaxometry. Comprehensive test-retest scan analyses using five 1.5-T and three 3.0-T systems from a single vendor including different scanner types across 3 institutions demonstrated that 3D MRF-derived morphological information and relaxation times are highly repeatable at both 1.5 T and 3.0 T. Regional cortical thickness and subcortical volume values showed high agreement and low bias across different field strengths. The ability to acquire a set of regional T1, T2, thickness, and volume measurements of neuroanatomical structures with high repeatability and reproducibility facilitates the ability of longitudinal multicenter imaging studies to quantitatively monitor changes associated with underlying pathologies, disease progression, and treatments.

Health-related quality of life and estimation of the minimally important difference in the Functional Assessment of Cancer Therapy-Endocrine Symptom score in postmenopausal ER+/HER2- metastatic breast cancer with low sensitivity to endocrine therapy.

BACKGROUND: The HORSE-BC study previously demonstrated that second-line endocrine therapy (ET) for patients with acquired endocrine-resistant metastatic breast cancer (MBC) still provided a clinically meaningful benefit. Herein, we investigated the health-related quality of life (HRQOL) in the HORSE-BC study. METHODS: Patients with acquired endocrine-resistant MBC who were scheduled for second-line ET were recruited. The HRQOL was assessed at baseline, and 1 and 3 months after second-line ET initiation. To investigate the minimally important difference (MID) in the Functional Assessment of Cancer Therapy-Endocrine Symptoms (FACT-ES), we evaluated the means and standard deviations for the distribution-based method, and differences in the change in HRQOL for the anchor-based method. We also investigated the association between FACT-ES total scores and clinical benefit. RESULTS: Overall, 56 patients were enrolled. Of these, 47 were analyzed. When defined as 1/3 standard deviation estimates based on the distribution method, the calculated MID was 5.9. The MIDs of the FACT-ES total scores based on the anchor method were 7.7 for decline and 4.1 for improvement. The MID decline proportions were 6.1% and 14.7% lower in patients who experienced clinical benefits than in those who did not at 1 and 3 months, respectively. The ratios of MID improvement in patients who experienced clinical benefits were 18.3% and 3.2% higher, respectively; the mean change in the FACT-ES total score from baseline improved in patients who experienced clinical benefits. CONCLUSIONS: Maintaining the HRQOL as determined by FACT-ES may be associated with clinical benefits in patients with acquired endocrine-resistant MBC treated with ET.

Rigid real-time prospective motion-corrected three-dimensional multiparametric mapping of the human brain.

PURPOSE: To develop a rigid real-time prospective motion-corrected multiparametric mapping technique and to test the performance of quantitative estimates. METHODS: Motion tracking and correction were performed by integrating single-shot spiral navigators into a multiparametric imaging technique, three-dimensional quantification using an interleaved Look-Locker acquisition sequence with a T2 preparation pulse (3D-QALAS). The spiral navigator was optimized, and quantitative measurements were validated using a standard system phantom. The effect of motion correction on whole-brain T1 and T2 mapping under different types of head motion during the scan was evaluated in 10 healthy volunteers. Finally, six patients with Parkinson's disease, which is known to be associated with a high prevalence of motion artifacts, were scanned to evaluate the effectiveness of our method in the real world. RESULTS: The phantom study demonstrated that the proposed motion correction method did not introduce quantitative bias. Improved parametric map quality and repeatability were shown in volunteer experiments with both in-plane and through-plane motions, comparable to the no-motion ground truth. In real-life validation in patients, the approach showed improved parametric map quality compared to images obtained without motion correction. CONCLUSIONS: Real-time prospective motion-corrected multiparametric relaxometry based on 3D-QALAS provided robust and repeatable whole-brain multiparametric mapping.

Cost-Effectiveness of Trastuzumab With or Without Chemotherapy as Adjuvant Therapy in HER2-Positive Elderly Breast Cancer Patients: A Randomized, Open-Label Clinical Trial, the RESPECT Trial.

BACKGROUND AND OBJECTIVE: Trastuzumab is a standard care as adjuvant chemotherapy (AdjCT) for patients with human epidermal growth factor receptor 2 (HER2)-positive primary breast cancer (BC) in Japan. However, no reports have evaluated its economics for patients with HER2-positive BC over 70 years of age. The objective of this study was to evaluate the cost-effectiveness of HER2-targeted trastuzumab + chemotherapy in Japan, comparing it with trastuzumab monotherapy. METHODS: A three-state-partitioned survival model was developed to evaluate the cost-effectiveness of trastuzumab + chemotherapy versus trastuzumab monotherapy for AdjCT in elderly patients with HER2-positive BC. We derived the efficacy data, utilities, and costs of both arms from individual patient data in the RESPECT trial (NCT01104935) and published studies. The costs and quality-adjusted life years (QALYs) were discounted at 2% per annum using a payer perspective. The respective cost estimates were reported in 2019 Japanese Yen (JPY) or US dollars (US$). The primary outcome was the incremental cost-effectiveness ratio (ICER). We assured robustness with deterministic and probabilistic sensitivity analyses. RESULTS: The cost per patient for trastuzumab + chemotherapy was JPY 14.6 million (US$137,000), and their QALYs were 9.308, compared with JPY 14.2 million (US$131,000) and 9.101, respectively, for trastuzumab monotherapy. The ICER of trastuzumab + chemotherapy versus trastuzumab monotherapy was JPY 2.7 milllion/QALY (US$17,200/QALY). The ICER for trastuzumab with chemotherapy varied from "Dominant" to "Dominated" in one-way sensitivity analysis. CONCLUSIONS: The base-case analysis suggests that AdjCT with trastuzumab + chemotherapy is likely to be a cost-effective choice for patients with HER2-positive BC aged 70 years or older. However, the sensitivity analysis suggested uncertainty regarding the cost-effectiveness of trastuzumab + chemotherapy.

Relational Design for Dementia and Job Significance (ReDeSign): Study protocol for a randomized controlled trial of an online dementia training for retail workers.

BACKGROUND: The need for dementia training for retail workers has been recognized by dementia-friendly initiatives. However, evidence for dementia training in non-healthcare workplaces is lacking, and dissemination is challenging due to constraints on private companies' time and finances. The online training program ReDeSign (Relational Design for Dementia and Job Significance) applies mobile micro-learning methods and Relational Design Theory against time and financial constraints, respectively, and is designed to improve work-related outcomes. METHODS: This study will evaluate the effectiveness of ReDeSign with a randomized controlled trial. One hundred and twenty-four convenience store workers in Tokyo will be recruited and randomly assigned to the intervention or control groups. ReDeSign consists of four contents relevant to the job: simulation games, lectures and quizzes, virtual contacts, and information about benefits to others. Self-reported surveys will be conducted for individual workers at baseline, one month later, and three months later. ReDeSign will be delivered to workers in the intervention (n = 62) and control (n = 62) groups immediately after the baseline survey and after the one-month survey, respectively. The primary outcome is the change of attitude toward people with dementia, and the secondary outcomes are dementia knowledge, helping behavior, job satisfaction, workers' intention to stay, and persistence. DISCUSSION: ReDeSign provides dementia training to convenience store workers and contributes to developing an inclusive community for people with dementia. The results of this study may provide a new strategy for the dissemination of dementia training in non-healthcare workplaces.