The Tokyo Oldest Old Survey on Total Health (TOOTH): A longitudinal cohort study of multidimensional components of health and well-being

<p>Abstract</p> <p>Background</p> <p>With the rapid worldwide increase in the oldest old population, considerable concern has arisen about the social and economic burden of diseases and disability in this age group. Understanding of multidimensional structure of health and its life-course trajectory is an essential prerequisite for effective health care delivery. Therefore, we organized an interdisciplinary research team consisting of geriatricians, dentists, psychologists, sociologists, and epidemiologists to conduct a longitudinal observational study.</p> <p>Methods/Design</p> <p>For the Tokyo Oldest Old Survey on Total Health (TOOTH) study, a random sample of inhabitants of the city of Tokyo, aged 85 years or older, was drawn from the basic city registry. The baseline comprehensive assessment consists of an in-home interview, a self-administered questionnaire, and a medical/dental examination. To perform a wide variety of biomedical measurements, including carotid ultrasonography and a detailed dental examination, participants were invited to our study center at Keio University Hospital. For those who were not able to visit the study center, we provided the option of a home-based examination, in which participants were simultaneously visited by a geriatrician and a dentist. Of 2875 eligible individuals, a total of 1152 people were recruited, of which 542 completed both the in-home interview and the medical/dental examination, with 442 completed the in-home interview only, and another 168 completed self or proxy-administered data collection only. Carotid ultrasonography was completed in 458 subjects, which was 99.6% of the clinic visitors (n = 460). Masticatory assessment using a colour-changeable chewing gum was completed in 421 subjects, a 91.5% of the clinic visitors.</p> <p>Discussion</p> <p>Our results demonstrated the feasibility of a new comprehensive study that incorporated non-invasive measurements of subclinical diseases and a detailed dental examination aiming at community-dwelling individuals aged 85 years or older. The bimodal recruitment strategy is critically important to capture a broad range of health profiles among the oldest old. Results form the TOOTH study will help develop new models of health promotion, which are expected to contribute to an improvement in lifelong health and well-being.</p> <p>Trial Registration</p> <p>This study has been registered in the UMIN-Clinical Trial Registry (CTR), ID: UMIN000001842.</p

Empathic / not empathic experience of mothers and nurses in early child care support scene after childbirth

育児支援場面において、母親と看護者の受け止め方から、双方の共感的、非共感的体験を明らかにする。対象は母親 7 名と看護者２名で、育児支援場面の参加観察及び、母親、看護者に半構成的面接を行った。分析は、逐語録から帰納的に内容の分析を行った。共感的体験では母親は 2 カテゴリー、［はりつめていた心がとける］［育児をしきりなおしたい］と 6 つのサブカテゴリーに大別された。看護者は 3 カテゴリー、［母親の気持ちを察し汲み取る受け止めと関わり］［母親を支え、気持ちに応える関わり］［母親の育児の状況、母親との関わりに満足する］と 7 つのサブカテゴリーに大別された。非共感的体験では母親は２カテゴリー、［看護者と理解しあえていないが、育児への肯定感情を抱く］［支援する看護者ではない育児のよりどころ］と 6 つのサブカテゴリーに大別された。看護者は 5 カテゴリー［母親の反応を理解したい］［母親の思いを察し、夫婦の選択に委ねる］［母親自身の育児の思いが反映されない関わり］［結果、状況を優先し、判断した関わり］［助言に対する母親の反応を解釈して、満足する］と 7 つのサブカテゴリーに大別された。共感的体験の中では、母親と看護者双方の受け止め方、思いが相互理解を感じ取り、その結果母親は、前向きな解決姿勢を持たせる満足感を得ていた。そしてそのことが看護者の満足感や安堵感につながっていた。This study was performed to examine the empathic and non-empathic experiences of mothers and nurses during early childcare support.Semi-structured interviews were conducted with seven mothers and two nurses engaged in childcare support.With regard to the empathic experiences, two categories ([loosening of tense feelings] and [childcare begins again on a new level]) and six sub-categories were derived from the mothers. For nurses, three categories ([relationship taking mothersʼ feelings into consideration], [relationship to support and empathize with mothers], and [accept the childcare of mothers and being satisfied with support given to mothers]) containing seven sub-categories were derived.With regard to the non-empathic experiences, we again derived two categories ([wants to take care of her baby but does not understand the nursesʼ advice] and [does not rely on nursesʼ support in childcare]) and six sub-categories for mothers. For nurses, we derived five categories ([want to understand mothersʼ responses], [infer mothersʼ feelings and respect couplesʼ choices], [relationships do not reflect mothersʼ parenting feelings], [relationships that prioritize results and situations], and [pleased to be able to interpret the mothersʼ reactions]) containing seven sub-categories.Mothersʼ and nursesʼ empathic experiences indicated that they had feelings of mutual understanding. As a result, mothers experienced satisfaction, which gave them a more positive attitude toward solving problems themselves. This led to greater satisfaction and relief among nursing staff

Nuclear Factor (Erythroid-Derived)-Related Factor 2-Associated Retinal Pigment Epithelial Cell Protection under Blue Light-Induced Oxidative Stress

Purpose. It is a matter of increasing concern that exposure to light-emitting diodes (LED), particularly blue light (BL), damages retinal cells. This study aimed to investigate the retinal pigment epithelium (RPE) damage caused by BL and to elucidate the role of nuclear factor (erythroid-derived)-related factor 2 (Nrf2) in the pathogenesis of BL-induced RPE damage. Methods. ARPE-19, a human RPE cell line, and mouse primary RPE cells from wild-type and Nrf2 knockout (Nrf2−/−) mice were cultured under blue LED exposure (intermediate wavelength, 450 nm). Cell death rate and reactive oxygen species (ROS) generation were measured. TUNEL staining was performed to detect apoptosis. Real-time polymerase chain reaction was performed on NRF2 mRNA, and western blotting was performed to detect Nrf2 proteins in the nucleus or cytoplasm of RPE cells. Results. BL exposure increased cell death rate and ROS generation in ARPE-19 cells in a time-dependent manner; cell death was caused by apoptosis. Moreover, BL exposure induced NRF2 mRNA upregulation and Nrf2 nuclear translocation in RPE. Cell death rate was significantly higher in RPE cells from Nrf2−/− mice than from wild-type mice. Conclusions. The Nrf2 pathway plays an important role in protecting RPE cells against BL-induced oxidative stress

AXL confers intrinsic resistance to osimertinib and advances the emergence of tolerant cells

A novel EGFR-tyrosine kinase inhibitor (TKI), osimertinib, has marked efficacy in patients with EGFR-mutated lung cancer. However, some patients show intrinsic resistance and an insufficient response to osimertinib. This study showed that osimertinib stimulated AXL by inhibiting a negative feedback loop. Activated AXL was associated with EGFR and HER3 in maintaining cell survival and inducing the emergence of cells tolerant to osimertinib. AXL inhibition reduced the viability of EGFR-mutated lung cancer cells overexpressing AXL that were exposed to osimertinib. The addition of an AXL inhibitor during either the initial or tolerant phases reduced tumor size and delayed tumor re-growth compared to osimertinib alone. AXL was highly expressed in clinical specimens of EGFR-mutated lung cancers and its high expression was associated with a low response rate to EGFR-TKI. These results indicated pivotal roles for AXL and its inhibition in the intrinsic resistance to osimertinib and the emergence of osimertinib-tolerant cells

Development of a novel automatic ascites filtration and concentration equipment with multi‐ring‐type roller pump units for cell‐free and concentrated ascites reinfusion therapy

Cell‐free and concentrated ascites reinfusion therapy (CART) is an effective therapy for refractory ascites. However, CART is difficult to perform as ascites filtration and concentration is a complicated procedure. Moreover, the procedure requires the constant assistance of a clinical engineer or/and the use of an expensive equipment for the multi‐purpose blood processing. Therefore, we developed a CART specialized equipment (mobility CART [M‐CART]) that could be used safely with various safety measures and automatic functions such as automatic washing of clogged filtration filter and self‐regulation of the concentration ratio. Downsizing, lightning of the weight, and automatic processing in M‐CART required the use of newly developed multi‐ring‐type roller pump units. This equipment was approved under Japanese regulations in 2018. In performing 41 sessions of CART (for malignant ascites, 22 sessions; and hepatic ascites, 19 sessions) using this equipment in 17 patients, no serious adverse event occurred. An average of 4494 g of ascites was collected and the total amount of ascites was processed in all the sessions without any trouble. The mean weight of the processed ascites was 560 g and the mean concentration ratio was 8.0. The ascites were processed at a flow rate of 50 mL/min. The mean ascites processing time was 112.5 minutes and a 106.5‐minutes (95.2%) ascites processing was performed automatically. The operator responded to alarms or support information 3.2 times on average (3.1 minutes, 2.1% of ascites processing time). Human errors related to ascites processing were detected by M‐CART at 0.4 times per session on average and were appropriately addressed by the operator. The frequencies of automatic washing of clogged filtration filter and self‐regulation of the concentration ratio were 31.7% and 53.7%, respectively. The mean recovery rates (recovery dose) of protein, albumin, and immunoglobulin G were 72.9%, 72.9%, and 71.2% (65.9 g, 34.9 g, and 13.2 g), respectively. Steroids were administered in 92.7% of the sessions to prevent fever and the mean increase in body temperature was 0.53°C. M‐CART is a compact and lightweight automatic CART specialized equipment that can safely and easily process a large quantity of ascites without the constant assistance of an operator

Prognostic impact of clinical factors for immune checkpoint inhibitor with or without chemotherapy in older patients with non-small cell lung cancer and PD-L1 TPS ≥ 50%

IntroductionThe proportion of older patients diagnosed with advanced-stage non-small cell lung cancer (NSCLC) has been increasing. Immune checkpoint inhibitor (ICI) monotherapy (MONO) and combination therapy of ICI and chemotherapy (COMBO) are standard treatments for patients with NSCLC and programmed cell death ligand-1 (PD-L1) tumor proportion scores (TPS) ≥ 50%. However, evidence from the clinical trials specifically for older patients is limited. Thus, it is unclear which older patients benefit more from COMBO than MONO.MethodsWe retrospectively analyzed 199 older NSCLC patients of Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 and PD-L1 TPS ≥ 50% who were treated with MONO or COMBO. We analyzed the association between treatment outcomes and baseline patient characteristics in each group, using propensity score matching.ResultsOf the 199 patients, 131 received MONO, and 68 received COMBO. The median overall survival (OS; MONO: 25.2 vs. COMBO: 42.2 months, P = 0.116) and median progression-free survival (PFS; 10.9 vs. 11.8 months, P = 0.231) did not significantly differ between MONO and COMBO group. In the MONO group, OS was significantly shorter in patients without smoking history compared to those with smoking history [HR for smoking history against non-smoking history: 0.36 (95% CI: 0.16-0.78), P = 0.010]. In the COMBO group, OS was significantly shorter in patients with PS 1 than those with PS 0 [HR for PS 0 against PS 1: 3.84 (95% CI: 1.44-10.20), P = 0.007] and for patients with squamous cell carcinoma (SQ) compared to non-squamous cell carcinoma (non-SQ) [HR for SQ against non-SQ: 0.17 (95% CI: 0.06-0.44), P &lt; 0.001]. For patients with ECOG PS 0 (OS: 26.1 months vs. not reached, P = 0.0031, PFS: 6.5 vs. 21.7 months, P = 0.0436) or non-SQ (OS: 23.8 months vs. not reached, P = 0.0038, PFS: 10.9 vs. 17.3 months, P = 0.0383), PFS and OS were significantly longer in the COMBO group.ConclusionsECOG PS and histological type should be considered when choosing MONO or COMBO treatment in older patients with NSCLC and PD-L1 TPS ≥ 50%