Discovery and informing research participants of incidental findings detected in brain magnetic resonance imaging studies : Review and multi‐institutional study

Background: Brain imaging studies using magnetic resonance imaging (MRI ) sometimes reveal incidental findings (IFs) that might be relevant to some of the health issues in research participants. Although professional communities have discussed how to manage these IFs, there is no global consensus on the concrete handling procedures including how to inform participants of IFs. Methods: First, this study reviewed previous studies for the number of IFs discovered in brain imaging studies using MEDLINE. Second, a multi‐institutional study determined the number of IF discoveries and evaluated the method of informing participants at multiple institutions, which participated in a national brain science project in Japan. Results: Both the review and multi‐institutional study showed that IFs with a high urgency level were discovered in 0–2.0% of participants, including healthy volunteers, and that the rate of IF discovery in general was higher in studies conducted in elderly population. Moreover, multi‐institutional study suggested the criteria used to judge whether or not to inform participants of IFs may differ by institution. Conclusions: Our results suggest that in order to ensure informing the participants of high urgency IFs, physicians who are capable of interpreting brain images clinically should review all brain images, and the establishment of a support system is required for brain imaging studies at nonmedical institutions. Since the method of informing participants of IFs might affect their understanding and acceptance of IFs, which are related to managing risks of false “clean bill of health” or psychological impacts of informing IFs, further research focusing on communication of IFs is needed

Multiple Physical Symptoms Are Useful to Identify High Risk Individuals for Burnout: A Study on Faculties and Hospital Workers in Japan

Healthcare workers have a high risk of burnout. This study aimed to investigate if the numbers of physical symptoms are associated with burnout among healthcare workers. We conducted a cross-sectional survey at a large university in Tokyo, Japan, in 2016. Participants were 1080: 525 faculties and 555 hospital workers. We investigated 16 physical symptoms perceived more than once per week and examined the association between the number of physical symptoms and Copenhagen Burnout Inventory (CBI); work-related (WBO), personal (PBO), and client-related (CBO) burnout. All CBI scores were higher among hospital workers than among faculties: WBO (43 vs. 29), PBO (50 vs. 33), CBO (33 vs. 29). Moreover, the higher the number of physical symptoms perceived, the higher the degree of burnout scores became (trend p-values < 0.001), except for CBO among faculties. Job strain (all except for CBO among hospital workers) and work-family conflict were associated with an increased risk of burnout. Being married (WBO and CBO among faculties), having a child (except for PBO and CBO among faculties), and job support (faculty and hospital workers with WBO and faculties with PBO) were associated with a decreased risk of burnout. Multiple physical symptoms might be useful for identifying high risk individuals for burnout

Continuous Work Support Checklist for Female Healthcare Workers: Scale Development and Validation

Healthcare jobs are very popular among women, however in Japan, women readily quit working because of gender-role responsibilities. This study aimed to develop a workplace support checklist for women to continue to work. In 2017, we investigated 780 (female 74.8%) faculty members and healthcare professionals of one medical university in Japan. We asked them to score the extent to which they considered 35 items identified by a task team, to be related to continuous work support for female workers in healthcare. We carried out an exploratory factor analysis and extracted four domains with 16 items in all: Support for child rearing and home care (five items), Information dissemination (five items), Active promotion of women workers to higher positions (three items), and Consulting and counseling service (three items), with Cronbach\u27s alpha values ranging from 0.88 to 0.92. We found that the first three factors were generally associated with reasonably relevant characteristics of being female, in their 30s, married, and members of faculty. We also found that women with Intention to leave the workplace underscored the importance of Support for child rearing and home care and Consulting and counseling service. These results suggest that the checklist is reliable and valid

Gender Division of Labor, Burnout, and Intention to Leave Work Among Young Female Nurses in Japan: A Cross-Sectional Study

Women in Japan face difficulties balancing work and personal life due to the gender division of labor, and medical professions are no exception. The purpose of this study was to investigate if the gender division of labor affects the intention to leave the workplace among the nursing profession. Among 328 female nurses working for three university-affiliated hospitals in Tokyo, Japan, above 70% were in their 20s and 30s and single, and agreed with the gender division of labor that men should be the breadwinner and women should assume family responsibilities. Adjusting for three types of Copenhagen burnout inventory, stepwise multivariable logistic regression models identified that being younger (all p-values < 0.05), each domain of burnout score (each p < 0.001 for work-, personal-, and client-related burnout) increased a risk of intention to leave, and high support decreased the risk (all p < 0.001). Women who agreed with the gender division of labor were more likely to have intentions to leave (p = 0.003 but this association disappeared when adjusted. The findings of study demonstrate that perceptions toward gender division of labor are not a determinant of intention to leave the workplace but the young nurses and those who scored high on burnout were the most vulnerable population

The Ras Target AF-6 is a Substrate of the Fam Deubiquitinating Enzyme

The Ras target AF-6 has been shown to serve as one of the peripheral components of cell–cell adhesions, and is thought to participate in cell–cell adhesion regulation downstream of Ras. We here purified an AF-6-interacting protein with a molecular mass of ∼220 kD (p220) to investigate the function of AF-6 at cell–cell adhesions. The peptide sequences of p220 were identical to the amino acid sequences of mouse Fam. Fam is homologous to a deubiquitinating enzyme in Drosophila, the product of the fat facets gene. Recent genetic analyses indicate that the deubiquitinating activity of the fat facets product plays a critical role in controlling the cell fate. We found that Fam accumulated at the cell–cell contact sites of MDCKII cells, but not at free ends of plasma membranes. Fam was partially colocalized with AF-6 and interacted with AF-6 in vivo and in vitro. We also showed that AF-6 was ubiquitinated in intact cells, and that Fam prevented the ubiquitination of AF-6

Impact of Bevacizumab Being Skipped due to Adverse Events of Special Interest for Bevacizumab in Patients with Unresectable Hepatocellular Carcinoma Treated with Atezolizumab plus Bevacizumab: An Exploratory Analysis of the Phase III IMbrave150 Study

Introduction: The phase III IMbrave150 study established atezolizumab + bevacizumab as the global standard of care in patients with unresectable hepatocellular carcinoma (HCC). This exploratory analysis examined the impact of bevacizumab interruption due to bevacizumab adverse events of special interest (AESIs). Methods: Patients in IMbrave150 who were randomized to atezolizumab + bevacizumab and received treatment for ≥6 months (to reduce immortal time bias) were included in group A-1 if bevacizumab had ever been skipped due to bevacizumab AESIs or to group A-2 otherwise. Efficacy analyses included overall survival (OS) and progression-free survival (PFS) by whether bevacizumab was skipped (group A-1 vs. A-2). PFS was evaluated per independent review facility (IRF)-assessed Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 and HCC-modified RECIST (IRF-HCC mRECIST). Safety was also evaluated. Results: Of the 210 patients who received ≥6 months of atezolizumab + bevacizumab, 69 were assigned to group A-1 and 141 to A-2. At data cutoff (August 20, 2020), hazard ratio (HR) for OS was 1.04 (95% CI: 0.64, 1.69) for group A-1 versus A-2. HR for PFS was 1.07 (95% CI: 0.74, 1.55) per IRF-assessed RECIST 1.1 and 1.10 (95% CI: 0.76, 1.59; 15.5 vs. 9.7 months) per IRF-HCC mRECIST for group A-1 versus A-2. Safety profiles for atezolizumab and bevacizumab were largely similar between groups. More group A-1 patients had grade 3/4 adverse events. A separate analysis investigating the impact of immortal time bias in patients who received ≥3 months of atezolizumab + bevacizumab supported the appropriateness of the ≥6-month landmark analysis. Discussion/Conclusion: Efficacy was similar between patients who skipped bevacizumab due to bevacizumab AESIs and those who did not. Although this comparison was nonrandomized and exploratory, results suggest that skipping bevacizumab due to bevacizumab AESIs did not considerably impact the efficacy and safety of atezolizumab + bevacizumab

Changes in conditional net survival and dynamic prognostic factors in patients with newly diagnosed metastatic prostate cancer initially treated with androgen deprivation therapy

Background The purpose of this study was to identify predictive factors associated with conditional net survival in patients with metastatic hormone-naive prostate cancer (mHNPC) initially treated with androgen deprivation therapy (ADT). Methods At nine hospitals in Tohoku, Japan, the medical records of 605 consecutive patients with mHNPC who initially received ADT were retrospectively reviewed. The Pohar Perme estimator was used to calculate conditional net cancer-specific survival (CSS) and overall survival (OS) for up to 5 years subsequent to the diagnosis. Using multiple imputation, proportional hazard ratios for conditional CSS and OS were calculated with adjusted Cox regression models. Results During a median follow up of 2.95 years, 208 patients died, of which 169 died due to progressive prostate cancer. At baseline, the 5-year CSS and OS rates were 65.5% and 58.2%, respectively. Conditional 5-year net CSS and OS survival gradually increased for all the patients. In patients given a 5-year survivorship, the conditional 5-year net CSS and OS rates improved to 0.906 and 0.811, respectively. Only the extent of disease score (EOD) >= 2 remained a prognostic factor for CSS and OS up to 5 years; as survival time increased, other variables were no longer independent prognostic factors. Conclusions The conditional 5-year net CSS and OS in patients with mHNPC gradually increased; thus, the risk of mortality decreased with increasing survival. The patient\u27s risk profile changed over time. EOD remained an independent prognostic factor for CSS and OS after 5-year follow-up. Conditional net survival can play a role in clinical decision-making, providing intriguing information for cancer survivors

Prognostic significance of early changes in serum biomarker levels in patients with newly diagnosed metastatic prostate cancer

We evaluated the impact of early changes in serum biomarker levels on the survival of patients with metastatic hormone-sensitive prostate cancer (mHSPC) who were initially treated with androgen deprivation therapy (ADT). We retrospectively investigated 330 patients with mHSPC whose serum maker levels were at baseline and at 2-4 months. An optimal Cox regression model was established with the highest optimism-corrected concordance index based on 10-fold cross-validation. The median cancer-specific survival (CSS) and overall survival (OS) were 7.08 and 6.47 years (median follow-up, 2.53 years), respectively. In the final optimal Cox model with serum biomarker levels treated as time-varying covariates, prostate-specific antigen (PSA), hemoglobin (Hb), and alkaline phosphatase (ALP) significantly increased the risk of poor survival in the context of both CSS and OS. Kaplan-Meier curves stratified by the three risk factors of high PSA, low Hb and high ALP desmondtated that median OS were not reached with none of these factors, 6.47 years with one or two factors, and 1.76 years with all three factors. Early changes in serum biomarker levels after ADT may be good prognostic markers for the survival of patients with mHSPC