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Rituximab-combined anthracycline-free chemotherapy in newly diagnosed paediatric and adolescent patients with non-high-risk aggressive mature B cell lymphoma: protocol for a single-arm, open-label, multicentre, phase II study (the Japan Childrens Cancer G

Por: Sekimizu · M. · Fukano · R. · Koga · Y. · Mitsui · T. · Fujita · N. · Mori · T. · Hori · D. · Tanaka · M. · Ohki · K. · Iwafuchi · H. · Nakazawa · A. · Mori · T. · Kobayashi · R. · Hashimoto · H. · M. Saito · A. · Kamei · M. · on behalf of Lymphoma Committee of Japan Childrens Cancer G
Introduction

Children and adolescents with mature B cell non-Hodgkin lymphoma (B-NHL) are treated with short-intensive chemotherapy. The burden of short-term and long-term toxicity is highly relative to its high cure rate in good-risk patients. Although the addition of rituximab to standard lymphome Malin B (LMB) chemotherapy markedly prolongs event-free survival and overall survival in high-risk patients, the benefit of rituximab in good-risk patients remains to be elucidated. This clinical trial will examine whether the addition of rituximab eliminates anthracyclines in good-risk patients without compromising treatment outcomes.

Methods and analysis

We will perform a single-arm, open-label, multicentre phase II study. Low-risk (stage I – completely resected, stage II abdominal) and intermediate-risk (stages I and II – incompletely resected; stage II – resected, other than abdominal; stage III with LDH x upper limit of normal) patients with newly diagnosed B-NHL are eligible. Low-risk patients receive two courses of R-COM1P (rituximab, cyclophosphamide, vincristine, methotrexate, prednisolone and intrathecal methotrexate with hydrocortisone), and intermediate-risk patients receive COP (cyclophosphamide, vincristine, prednisolone and intrathecal methotrexate with hydrocortisone) followed by two courses each of R-COM3P and R-CYM (rituximab, cytarabine, methotrexate and intrathecal methotrexate with hydrocortisone). The primary endpoint is a 3-year event-free survival rate in paediatric patients (

Ethics and dissemination

This research was approved by the Certified Review Board at NHO Nagoya Medical Center (Nagoya, Japan) on 21 September 2021. Written informed consent is obtained from all patients and/or their guardians. The results of this study will be disseminated through peer-reviewed publications and conference presentations.

Study registration

Japan Registry of Clinical Trials, jRCTs041210104.

Identification of the reporter gene combination that shows high contrast for cellular level MRI

by Naoya Hayashi, Junichi Hata, Tetsu Yoshida, Daisuke Yoshimaru, Yawara Haga, Hinako Oshiro, Ayano Oku, Noriyuki Kishi, Takako Shirakawa, Hideyuki Okano

Currently, we can label the certain cells by transducing specific genes, called reporter genes, and distinguish them from other cells. For example, fluorescent protein such as green fluorescence protein (GFP) is commonly used for cell labeling. However, fluorescent protein is difficult to observe in living animals. We can observe the reporter signals of the luciferin-luciferase system from the outside of living animals using in vivo imaging systems, although the resolution of this system is low. Therefore, in this study, we examined the reporter genes, which allowed the MRI-mediated observation of labeled cells in living animals. As a preliminary stage of animal study, we transduced some groups of plasmids that coded the protein that could take and store metal ions to the cell culture, added metal ions solutions, and measured their T1 or T2 relaxation values. Finally, we specified the best reporter gene combination for MRI, which was the combination of transferrin receptor, DMT1, and Ferritin-M6A for T1WI, and Ferritin-M6A for T2WI.

Consumption of ultra-processed foods and low dietary diversity are associated with sedentary and unhealthy eating behaviors: A nationwide study with Brazilian Schoolchildren

by Giovanna Angela Leonel Oliveira, Vivian Siqueira Santos Gonçalves, Eduardo Yoshio Nakano, Natacha Toral

Background

Consumption of ultra-processed foods and low dietary diversity are risk factors for chronic diseases.

Aim

To evaluate the association between food consumption and sedentary and unhealthy eating behaviors of Brazilian schoolchildren between 6 and 11 years old.

Methods

Cross-sectional study. A prevalence sample was calculated considering the number of children enrolled in elementary school. This sample was distributed proportionally to Brazil’s macro-regions and the type of school (public or private). The questionnaire was developed in Google Forms and disseminated through the snowball technique. The questionnaire was filled in by the children’s parents, with information about the child’s identification and health. Afterward, the child completed a questionnaire by her/himself. We used the previously validated Illustrated Questionnaire on Food Consumption for Brazilian Schoolchildren and the Illustrated Questionnaire on Eating and Sedentary Behaviors. Food consumption was analyzed using the NOVA score and the dietary diversity score. Poisson’s regression with robust variance was performed (p Results

The study included 2,021 dyads. Of these, 27.6% of children reported eating five or more ultra-processed foods and 39.0% four or fewer natural or staple foods the previous day. Using screens, proxy of sedentary behavior (Prevalence Ratio–PR = 1.8, Confidence Interval–CI95%1.2–2.8) and eating at irregular hours (PR = 1.6, CI95%1.2–2.2) were risk factors for high consumption of ultra-processed foods and low dietary diversity in schoolchildren. In addition, eating the three main meals on the previous day (PR = 0.6, CI95%0.4–0.8) was identified as protective factors against the consumption of ultra-processed foods and in favor of dietary diversity among schoolchildren.

Conclusion

Sedentary and unhealthy eating behaviors were associated with the consumption of ultra-processed foods and low dietary diversity in Brazilian schoolchildren.

Non-infectious diseases in infectious disease consultation: A descriptive study in a tertiary care teaching hospital

by Yoshiro Hadano, Takanori Matsumoto

In this retrospective study, we aimed to investigate the frequency, trend, and nature of non-infectious diseases (non-IDs) as the final diagnosis for patients during an infectious disease (ID) consultation in an acute care hospital in Japan. This study included adult inpatients who underwent ID consultations between October 2016 and March 2018. The demographic data, clinical manifestations, and final non-ID diagnoses of cases were explored. Among the 502 patients who underwent ID consultations, 45 (9.0%) were diagnosed with non-IDs. The most common diagnoses were tumors (22.2%, n = 10), connective tissue and collagen vascular diseases (13.3%, n = 6), other inflammatory diseases (8.9%, n = 4), and drug-induced fever (8.9%, n = 4). Multiple logistic regression analysis showed that the presence of consultations for diagnosis (odds ratio [OR], 22.0; 95% confidence interval [CI], 10.1–48.2; p

Measuring patients' experiences of continuity of care in a primary care context—Development and evaluation of a patient‐reported experience measure

Abstract

Background

Continuity of care is viewed as a hallmark of high-quality care in the primary care context. Measures to evaluate the quality of provider performance are scarce, and it is unclear how the assessments correlate with patients' experiences of care as coherent and interconnected over time, consistent with their preferences and care needs.

Aim

To develop and evaluate a patient-reported experience measure of continuity of care in primary care for patients with complex care needs.

Method

The study was conducted in two stages: (1) development of the instrument based on theory and empirical studies and reviewed for content validity (16 patients with complex care needs and 8 experts) and (2) psychometric evaluation regarding factor structure, test–retest reliability, internal consistency reliability, and convergent validity. In all, 324 patients participated in the psychometric evaluation.

Results

The Patient Experienced Continuity of care Questionnaire (PECQ) contains 20 items clustered in four dimensions of continuity of care measuring Information (four items), Relation (six items), Management (five items), and Knowledge (five items). Overall, the hypothesized factor structure was indicated. The PECQ also showed satisfactory convergent validity, internal consistency, and stability.

Conclusion/Implications

The PECQ is a multidimensional patient experience instrument that can provide information on various dimensions useful for driving quality improvement strategies in the primary care context for patients with complex care needs.

Patient or Public Contribution

Patients have participated in the content validation of the items.

Clarithromycin overcomes stromal cell-mediated drug resistance against proteasome inhibitors in myeloma cells via autophagy flux blockage leading to high NOXA expression

by Shota Moriya, Hiromi Kazama, Hirotsugu Hino, Naoharu Takano, Masaki Hiramoto, Shin Aizawa, Keisuke Miyazawa

We previously reported that macrolide antibiotics, such as clarithromycin (CAM), blocked autophagy flux, and simultaneous proteasome and autophagy inhibition by bortezomib (BTZ) plus CAM resulted in enhanced apoptosis induction in multiple myeloma (MM) cells via increased endoplasmic reticulum (ER) stress loading. However, in actual therapeutic settings, cell adhesion-mediated drug resistance between bone marrow stromal cells (BMSC) and MM cells has been known to be a barrier to treatment. To investigate whether CAM could enhance BTZ-induced cytotoxicity in MM cells under direct cell adhesion with BMSC, we established a co-culture system of EGFP-labeled MM cells with BMSC. The cytotoxic effect of BTZ on MM cells was diminished by its interaction with BMSC; however, the attenuated cytotoxicity was recovered by the co-administration of CAM, which upregulates ER stress loading and NOXA expression. Knockout of NOXA in MM cells canceled the enhanced cell death by CAM, indicating that NOXA is a key molecule for cell death induction by the co-administration of CAM. Since NOXA is degraded by autophagy as well as proteasomes, blocking autophagy with CAM resulted in the sustained upregulation of NOXA in MM cells co-cultured with BMSC in the presence of BTZ. Our data suggest that BMSC-associated BTZ resistance is mediated by the attenuation of ER stress loading. However, the addition of CAM overcomes BMSC-associated resistance via upregulation of NOXA by concomitantly blocking autophagy-mediated NOXA degradation and transcriptional activation of NOXA by ER stress loading.

Impact of home‐visit nursing service use on costs in the last 3 months of life among older adults: A retrospective cohort study

Abstract

Introduction

Considering Japan's aging society, the number of older individuals who die at home is expected to increase. In Japan, there are challenges in utilizing and promoting home-visit nursing services at the end of life for community-dwelling older adults. We examined the use of home-visit nursing services at the end of patients' lives and the recommended use patterns of this service (utilization, timing of initiation, and continuity) that contribute to reducing the medical care and long-term care costs (total costs) in the last 3 months of life.

Design

This was a retrospective cohort study.

Methods

We examined 33 municipalities in Japan, including depopulated areas. The analysis included 22,927 people aged 75 or older who died between September 2016 and September 2018. We used monthly medical care and long-term care insurance claims data. Participants were classified into five groups based on their history of home-visit nursing service use: (1) early initiation/continuous use, (2) early initiation/discontinued or fragment use, (3) not-early initiation/continuous use, (4) not-early initiation/fragment use, and (5) no use. Univariate and multivariate linear regression analyses were performed to examine the association between total costs in the last 3 months of life and patterns of home-visit nursing service use.

Results

Overall, the median age was 85, and 12,217 participants were men (53.3%). In the last half year before death, 5424 (23.7%) older adults used home-visit nursing services. Multivariable linear regression analysis of the log10-transformed value of total costs revealed that compared with the no use group, the early initiation/continuous use group was estimated to have 0.88 times (95% confidence interval: 0.84, 0.93) the total costs in the last 3 months of life (p < 0.001).

Conclusion

Early initiation use of home-visit nursing services may contribute to reducing total costs in the last 3 months of life for Japanese people aged 75 years or older living at home as they approach the end of life.

Clinical relevance

When approaching the end of life, many older adults require daily life care and palliative care. Policymakers are strengthening end-of-life care for community-dwelling older adults in Japan. Although the current results do not demonstrate the effectiveness of home-visit nursing services, they provide a perspective from which to assess the use of home-visit nursing services and its impact on older adults. The findings can be helpful in considering how to provide nursing care in home-care settings for older adults who prefer to spend their final days at home.

The impact of organizational compassion in health care on clinicians: A scoping review

Abstract

Background

The unprecedented exodus of workers from the healthcare system is a patient safety crisis. Organizational compassion in health care is the proactive, systematic, and continuous identification, alleviation, and prevention of all sources of suffering.

Aims

This scoping review aimed to describe the evidence regarding the impact of organizational compassion on clinicians, identify gaps, and provide recommendations for future research.

Methods

A comprehensive librarian-assisted database search was conducted. Databases searched were PubMed, SCOPUS, EMBASE, Web of Science, PsychInfo, and Business Source Complete. Combinations of search terms regarding health care, compassion, organizational compassion, and workplace suffering were used. The search strategy was limited to English language articles and those published between 2000 and 2021.

Results

Database search yielded 781 articles. After removing duplicates, 468 were screened by title and abstract, and 313 were excluded. One-hundred and fifty-five underwent full-text screening, and 137 were removed, leaving 18 eligible articles, two of which were set in the United States. Ten articles evaluated barriers or facilitators to organizational compassion, four evaluated elements of compassionate leadership, and four evaluated the Schwartz Center Rounds intervention. Several described the need to create systems that are compassionate to clinicians. Lack of time, support staff, and resources impeded the delivery of such interventions.

Linking evidence to action

Little research has been done to understand and evaluate the impact of compassion on US clinicians. Given the workforce crisis in American health care and the potential positive impact of increasing compassion for clinicians, there is an urgent need for researchers and healthcare administrators to fill this gap.

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