Academic clinician frontline-worker wellbeing and resilience during the COVID-19 pandemic experience: Were there gender differences?

Prior research suggests COVID-19 has amplified stress on Academic Clinician Frontline-Workers (ACFW). The aim of this paper is: (1) to better understand the experiences of ACFW during the COVID-19 pandemic including their mental-emotional wellbeing, academic productivity, clinical experiences, and (2) to examine any gender differences. A cross-sectional survey was administered to University of Minnesota/M Health Fairview systems' faculty February-June 2021. Of the 291 respondents, 156 were clinicians, with 91 (58 %) identifying as Frontline-Workers (ACFW). Faculty wellbeing was assessed using validated measures in addition to measures of productivity and sociodemographics. For example, ACFW reported a higher Work-Family Conflict (WFC) scores compared to non-ACFW (26.5 vs. 24.1, p = 0.057) but did not report higher Family-Work Conflict (FWC) scores (17.7 vs. 16.3, p = 0.302). Gender sub-analyses, revealed that women ACFW compared to men ACFW reported higher WFC scores (27.7 vs. 24.1, p = 0.021) and FWC (19.3 vs. 14.3, p = 0.004). Academically, ACFW reported submitting fewer grants and anticipated delays in promotion and tenure due to the COVID-19 (p = 0.035). Results suggest COVID-19 has exacerbated ACFW stress and gender inequities. Reports of anticipated delay in promotion for ACFW may pose a challenge for the long-term academic success of ACFW, especially women ACFW. In addition, women may experience higher FWC and WFC as compared to men. Schools of academic medicine should consider re-evaluating promotion/tenure processes and creating resources to support women ACFW as well as ACFW caregivers.

Early work patterns for gynaecological cancer survivors in the USA.

BACKGROUND: Little is known about the balance between work demands and treatment plans for >4.3 million working-age cancer survivors in the USA. AIMS: To describe changes in work status for gynaecological cancer survivors during the first 6 months following diagnosis and their experience with their employers' programmes and policies. METHODS: One hundred and ten gynaecological cancer survivors who were working at the time of their cancer diagnosis completed a survey. Case record reviews documented their clinical characteristics and treatment details. RESULTS: Ninety-five women (86%) had surgery; 81 (74%) received chemotherapy, radiotherapy or both in addition to surgery. Nine per cent of women said that they changed their treatment plan because of their jobs; in contrast, 62% of women said that they changed their work situation to accommodate their treatment plan. Overall, the most common month for women to stop working was Month 1 (41%), to decrease hours was Month 2 (32%) and to increase hours was Month 6 (8%). Twenty-eight per cent of women were aware of employer policies that assisted the return to work process; 70% of women were familiar with the Family and Medical Leave Act (FMLA) and 56% with the Americans with Disabilities Act (ADA). Only 26% completed a formal request for work accommodations. After 6 months, 56 of 83 women (67%) remained working or had returned to work. CONCLUSIONS: Work patterns varied for these gynaecological cancer survivors over the first 6 months following diagnosis. Opportunities exist to improve communication about work and treatment expectations between cancer survivors, occupational health professionals, employers and treating clinicians.

AAV-P125A-endostatin and paclitaxel treatment increases endoreduplication in endothelial cells and inhibits metastasis of breast cancer.

Endostatin potentiates the antimitotic effects of paclitaxel (taxol) on endothelial cells (ECs). P125A-endostatin and taxol-treated ECs showed multipolar spindles and nuclear lobulation, leading to mitotic catastrophe and cell death. Induction of nuclear abnormalities was found to be dependent on ß-catenin levels as wnt-mediated overexpression of ß-catenin reversed the changes in nuclear morphology. These results prompted us to investigate whether antiangiogenic gene therapy and paclitaxel chemotherapy can synergistically inhibit angiogenesis and tumor growth. We first determined the effect of combination treatment in a transgenic mouse model of breast cancer. Intramuscular injection of recombinant adeno-associated virus type-2 virus induced sustained expression of P125A-endostatin. In vivo studies showed that combination therapy inhibited mammary cancer growth, delayed the onset of multifocal mammary adenocarcinomas, decreased tumor angiogenesis and increased survival in treated mice. In a second model, female athymic mice were orthotopically transplanted with a metastatic human breast cancer cell line. Antiangiogenic gene therapy in combination with paclitaxel inhibited tumor angiogenesis and lung/lymph-node metastasis in this model. These studies demonstrate cooperation between endostatin gene therapy and chemotherapy to inhibit tumor initiation, growth and metastasis.

Radiation therapy with concomitant and adjuvant cisplatin and paclitaxel in high-risk cervical cancer: long-term follow-up.

INTRODUCTION: Chemo-potentiation of radiation improves survival in women with cervical cancer. Our group has previously demonstrated the tolerability of weekly paclitaxel combined with cisplatin during radiation therapy. We sought to determine the efficacy of this regimen in patients with "high risk" cervical cancer, and to determine the short- and long-term toxicity of this approach. METHODS: We prospectively enrolled surgically staged patients with positive peritoneal cytology, resectable nodal metastases, or primary tumor > 6 cm. Patients were treated using external beam radiation with concomitant cisplatin (50 mg/m2) during weeks 1, 4, and 7, and weekly paclitaxel (50 mg/m2), followed by four courses of adjuvant cisplatin (50 mg/m2) and paclitaxel (135 mg/m2). Toxicity, overall, and disease-free survival were evaluated. RESULTS: Twenty-three patients were enrolled, and 21 were evaluable. Patient allotment by FIGO stage was: IB1 - seven, IB2 - five, IIA - two, IIB - four, IIIB - two, IV - three. Twenty patients (95%) completed radiation treatment (median dose to point A was 8278 cGy). Seventeen patients (81%) completed all chemotherapy. At a median follow-up of 58 months the overall survival was 68%. Overall survival for patients with clinical Stage I and II disease was 82% at a median of 64 months. Hematologic toxicity was common but rarely resulted in treatment delays. Late complications requiring intervention (obstruction, fistula, significant lymphocyst) occurred in 11 patients (52%). CONCLUSION: The combination of paclitaxel and cisplatin appears efficacious in "high-risk" cervical cancer patients. Hematologic toxicity was common but tolerable. Long-term survival was common in these patients, however late toxicity was significant. This regimen should be investigated in collaborative phase III trials.

Adeno-associated virus-mediated delivery of a mutant endostatin suppresses ovarian carcinoma growth in mice.

Earlier studies have shown that a point mutation in human endostatin at position 125 (human endostatin wherein proline 125 was substituted with alanine, P125A-endostatin) improves endothelial cell binding and antiangiogenic activity. In the present study, we investigated the effect of recombinant adeno-associated virus (rAAV)-mediated gene delivery of P125A-endostatin (rAAV-P125Aendo) in a mouse model of ovarian carcinoma. Intramuscular (i.m.) injection of rAAV-P125Aendo resulted in a dose-dependent increase in serum endostatin levels. Consequently, vascular endothelial growth factor- and basic fibroblast growth factor-mediated angiogenesis was significantly inhibited in mice injected with rAAV-P125Aendo as compared to control mice injected with rAAV-LacZ. Furthermore, gene therapy using rAAV-P125Aendo construct showed sustained secretion of P125A-endostatin for up to 9 weeks after a single i.m. administration. Recombinant AAV-P125Aendo injection significantly inhibited the growth of human ovarian cancer cells in athymic nude mice. Immunofluorescence studies of residual tumors surgically removed from the rAAV-P125Aendo-treated animals showed decreased number of vessel ends and vessel length, indicating inhibition of angiogenesis. These studies suggest that recombinant AAV-mediated antiangiogenic gene therapy methods can be used to inhibit ovarian cancer growth.