症例登録速度が緩やかな検証的ランダム化試験における効率的な適応的症例数設計法の提案

学位の種別: 論文博士審査委員会委員 : （主査）東京大学教授 赤林 朗, 東京大学特任教授 森 武俊, 東京大学准教授 馬淵 昭彦, 東京大学准教授 島津 明人, 東京大学准教授 今井 健University of Tokyo(東京大学

無歯顎患者における概形印象の精度に関する3次元評価 : 研究用模型と作業用模型の3次元形状の比較

Purpose: The aim of this study was to compare 3-dimensional surfaces of study and working casts for edentulous jaws and to evaluate the accuracy of preliminary impressions with a view to the future application of digital dentistry for edentulous jaws. Methods: Forty edentulous volunteers were serially recruited. Nine dentists took preliminary and final impressions in a routine clinical work-up. The study and working casts were digitized using a dental 3-dimensional scanner. The two surface images were superimposed through a least-square algorithm using imaging software and compared qualitatively. Furthermore, the surface of each jaw was divided into 6 sections, and the difference between the 2 images was quantitatively evaluated. Results: Overall inspection showed that the difference around residual ridges was small and that around borders were large. The mean differences in the upper and lower jaws were 0.26 mm and 0.45 mm, respectively. The maximum values of the differences showed that the upward change mainly occurred in the anterior residual ridge, and the downward change mainly in the posterior border seal, and the labial and buccal vestibules, whereas every border of final impression was shortened in the lower jaw. The accuracy in all areas except the border, which forms the foundation, was estimated to be less than 0.25 mm. Conclusion: Using digital technology, we here showed the overall and sectional accuracy of the preliminary impression for edentulous jaws. In our clinic, preliminary impressions have been made using an alginate material while ensuring that the requisite impression area was covered

Randomized phase II study to determine the optimal dose of 3-week cycle nab-paclitaxel in patients with metastatic breast cancer

Background Chemotherapy-induced peripheral neuropathy is commonly observed in patients treated with nanoparticle albumin–bound paclitaxel (nab-PTX). We conducted a multicenter randomized controlled study to evaluate the optimal dose of nab-PTX. Methods We compared three different doses of q3w nab-PTX (Standard: 260 mg/m2 [SD260] vs Medium: 220 mg/m2 [MD220] vs Low: 180 mg/m2 [LD180]) in patients with HER2-negative metastatic breast cancer (MBC). Primary endpoint was progression-free survival (PFS). Grade 3/4 neuropathy rates in the three doses were estimated using the logistic regression model. The optimal dose was selected in two steps. Initially, if the hazard ratio (HR) for PFS was 1.33, the inferior dose was excluded, and we proceeded with the non-inferior dose. Then, if the estimated incidence rate of grade 3/4 neurotoxicity exceeded 10%, that dose was also excluded. Results One hundred forty-one patients were randomly assigned to SD260 (n = 47), MD220 (n = 46), and LD180 (n = 48) groups, and their median PFS was 6.66, 7.34, and 6.82 months, respectively. The HRs were 0.73 (95% confidence interval [CI]: 0.42–1.28) in MD220 vs SD260, 0.77 (95% CI 0.47–1.28) in LD180 vs SD260, and 0.96 (95% CI 0.56–1.66) in LD180 vs MD220. SD260 was inferior to MD220 and was excluded. The estimated incidence rate of grade 3/4 neurotoxicity was 29.5% in SD260, 14.0% in MD220, and 5.9% in LD180. The final selected dose was LD180. Conclusions Intravenous administration of low-dose nab-PTX at 180 mg/m2 q3w may be the optimal therapy with meaningful efficacy and favorable toxicity in patients with MBC

Association of Genetic Polymorphism with Taxane-induced Peripheral Neuropathy: Sub-analysis of a Randomized Phase II Study to Determine the Optimal Dose of 3-week Cycle Nab-Paclitaxel in Metastatic Breast Cancer Patients

Chemotherapy-induced peripheral neuropathy (CIPN) is an important clinical challenge that threatens patients’ quality of life. This sub-study of the ABROAD trial investigated the influence of single nucleotide polymorphisms (SNPs) on CIPN, using genotype data from a randomized study to determine the optimal dose of a 3-week-cycle regimen of nab-paclitaxel (q3w nab-PTX) in patients with metastatic breast cancer (MBC). Patients with HER2-negative MBC were randomly assigned to three doses of q3w nab-PTX (SD: 260 mg/m2 vs. MD: 220 mg/m2 vs. LD: 180 mg/m2). Five SNPs (EPHA4-rs17348202, EPHA5-rs7349683, EPHA6-rs301927, LIMK2-rs5749248, and XKR4-rs4737264) were analyzed based on the results of a previous genome-wide association study. Per-allele SNP associations were assessed by a Cox regression to model the cumulative dose of nab-PTX up to the onset of severe or worsening sensory neuropathy. A total of 141 patients were enrolled in the parent study; 91(65%) were included in this sub-study. Worsening of CIPN was significantly greater in the cases with XKR4 AC compared to those with a homozygote AA (HR 1.86, 95%CI: 1.00001−3.46, p=0.049). There was no significant correlation of CIPN with any other SNP. A multivariate analysis showed that the cumulative dose of nab-PTX was most strongly correlated with CIPN (p<0.01)

Long‐term care facilities' response to the COVID ‐19 pandemic: An international, cross‐sectional survey

Aims To (i) assess the adherence of long‐term care (LTC) facilities to the COVID‐19 prevention and control recommendations, (ii) identify predictors of this adherence and (iii) examine the association between the adherence level and the impact of the pandemic on selected unfavourable conditions. Design Cross‐sectional survey. Methods Managers (n = 212) and staff (n = 2143) of LTC facilities (n = 223) in 13 countries/regions (Brazil, Egypt, England, Hong Kong, Indonesia, Japan, Norway, Portugal, Saudi Arabia, South Korea, Spain, Thailand and Turkey) evaluated the adherence of LTC facilities to COVID‐19 prevention and control recommendations and the impact of the pandemic on unfavourable conditions related to staff, residents and residents' families. The characteristics of participants and LTC facilities were also gathered. Data were collected from April to October 2021. The study was reported following the STROBE guidelines. Results The adherence was significantly higher among facilities with more pre‐pandemic in‐service education on infection control and easier access to information early in the pandemic. Residents' feelings of loneliness and feeling down were the most affected conditions by the pandemic. More psychological support to residents was associated with fewer residents' aggressive behaviours, and more psychological support to staff was associated with less work–life imbalance. Conclusions Pre‐pandemic preparedness significantly shaped LTC facilities' response to the pandemic. Adequate psychological support to residents and staff might help mitigate the negative impacts of infection outbreaks. Impact This is the first study to comprehensively examine the adherence of LTC facilities to COVID‐19 prevention and control recommendations. The results demonstrated that the adherence level was significantly related to pre‐pandemic preparedness and that adequate psychological support to staff and residents was significantly associated with less negative impacts of the pandemic on LTC facilities' staff and residents. The results would help LTC facilities prepare for and respond to future infection outbreaks. Patient or public contribution No Patient or Public Contribution

Increased Red Blood Cell Distribution Width in the First Year after Diagnosis Predicts Worsening of Systemic Sclerosis-Associated Interstitial Lung Disease at 5 Years: A Pilot Study

The course of systemic sclerosis-associated interstitial lung disease (SSc-ILD) varies among individuals. Red blood cell distribution width (RDW) has been reported to be a predictor of idiopathic pulmonary fibrosis. However, there are no studies on the relationship between RDW and SSc-ILD. We conducted a retrospective study of 28 patients who were diagnosed with SSc-ILD on their first visit to our hospital and were followed-up for 5 years. The correlation between the changes in RDW, KL-6, and SP-D (&Delta;RDW, &Delta;KL-6, &Delta;SP-D) and the changes in percent-predicted forced lung volume and % carbon monoxide diffusion (&Delta;%FVC, &Delta;%DLco) was investigated. &Delta;RDW at 1 year after diagnosis was significantly inversely correlated with &Delta;%FVC at 5 years after diagnosis (r = &minus;0.51, p &lt; 0.001) and &Delta;%DLco at 5 years after diagnosis (r = &minus;0.47, p &lt; 0.001), whereas &Delta;KL-6 and &Delta;SP-D at 1 year were not correlated with &Delta;%FVC or &Delta;%DLco at 5 years. In the group of SSc-ILD patients with RDW increase in the first year after diagnosis, %FVC and %DLco were significantly lower than baseline at 3-, 4-, and 5-year assessments. In the group of patients without RDW increase in the first year, %FVC and %DLco did not decrease during the follow-up period. In conclusion, the changes in RDW in the first year after diagnosis may be useful surrogate markers to predict the long-term course of SSc-ILD