Background: Recurrent gynecological clear cell carcinoma (rGCCC) has a low objective response rate (ORR) to chemotherapy. Previous preclinical and clinical data suggest a potential synergy between immune checkpoint inhibitors and bevacizumab in rGCCC.Dostarlimab, a humanized monoclonal antibody targeting programmed cell death protein 1 (PD-1), combined with the anti-angiogenic bevacizumab, presents a novel therapeutic approach. This study will investigate the efficacy of dostarlimab +/− bevacizumab in rGCCC. Methods DOVE is a global, multicenter, international, open-label, randomized phase 2 study of dostarlimab +/− bevacizumab with standard chemotherapy in rGCCC. We will enroll 198 patients with rGCCC and assign them to one of three groups in a 1:1:1 ratio: arm A (dostarlimab monotherapy), B (dostarlimab + bevacizumab), and C (investigator’s choice of chemotherapy [weekly paclitaxel, pegylated liposomal doxorubicin, doxorubicin, or gemcitabine]). Patients with disease progression in arm A or C will be allowed to cross over to arm B. Stratification factors include prior bevacizumab use, prior lines of therapy (1 vs. >1), and primary site (ovarian vs. non-ovarian). Key inclusion criteria are histologically proven recurrent or persistent clear cell carcinoma of the ovary, endometrium, cervix, vagina, or vulva; up to five prior lines of therapy; disease progression within 12 months after platinumbased chemotherapy; and measurable disease. Key exclusion criteria are prior treatment with an anti–PD-1, anti–programmed death-ligand 1, or anti–programmed death-ligand 2 agent.The primary endpoint is progression-free survival determined by investigators. Secondary endpoints are ORR, disease control rate, clinical benefit rate, progression-free survival 2, overall survival, and toxicity. Exploratory objectives include immune biomarkers.

Background: Recurrent gynecological clear cell carcinoma (rGCCC) has a low objective response rate (ORR) to chemotherapy. Previous preclinical and clinical data suggest a potential synergy between immune checkpoint inhibitors and bevacizumab in rGCCC.Dostarlimab, a humanized monoclonal antibody targeting programmed cell death protein 1 (PD-1), combined with the anti-angiogenic bevacizumab, presents a novel therapeutic approach. This study will investigate the efficacy of dostarlimab +/− bevacizumab in rGCCC. Methods DOVE is a global, multicenter, international, open-label, randomized phase 2 study of dostarlimab +/− bevacizumab with standard chemotherapy in rGCCC. We will enroll 198 patients with rGCCC and assign them to one of three groups in a 1:1:1 ratio: arm A (dostarlimab monotherapy), B (dostarlimab + bevacizumab), and C (investigator’s choice of chemotherapy [weekly paclitaxel, pegylated liposomal doxorubicin, doxorubicin, or gemcitabine]). Patients with disease progression in arm A or C will be allowed to cross over to arm B. Stratification factors include prior bevacizumab use, prior lines of therapy (1 vs. >1), and primary site (ovarian vs. non-ovarian). Key inclusion criteria are histologically proven recurrent or persistent clear cell carcinoma of the ovary, endometrium, cervix, vagina, or vulva; up to five prior lines of therapy; disease progression within 12 months after platinumbased chemotherapy; and measurable disease. Key exclusion criteria are prior treatment with an anti–PD-1, anti–programmed death-ligand 1, or anti–programmed death-ligand 2 agent.The primary endpoint is progression-free survival determined by investigators. Secondary endpoints are ORR, disease control rate, clinical benefit rate, progression-free survival 2, overall survival, and toxicity. Exploratory objectives include immune biomarkers.

Background: Recurrent gynecological clear cell carcinoma (rGCCC) has a low objective response rate (ORR) to chemotherapy. Previous preclinical and clinical data suggest a potential synergy between immune checkpoint inhibitors and bevacizumab in rGCCC.Dostarlimab, a humanized monoclonal antibody targeting programmed cell death protein 1 (PD-1), combined with the anti-angiogenic bevacizumab, presents a novel therapeutic approach. This study will investigate the efficacy of dostarlimab +/− bevacizumab in rGCCC. Methods DOVE is a global, multicenter, international, open-label, randomized phase 2 study of dostarlimab +/− bevacizumab with standard chemotherapy in rGCCC. We will enroll 198 patients with rGCCC and assign them to one of three groups in a 1:1:1 ratio: arm A (dostarlimab monotherapy), B (dostarlimab + bevacizumab), and C (investigator’s choice of chemotherapy [weekly paclitaxel, pegylated liposomal doxorubicin, doxorubicin, or gemcitabine]). Patients with disease progression in arm A or C will be allowed to cross over to arm B. Stratification factors include prior bevacizumab use, prior lines of therapy (1 vs. >1), and primary site (ovarian vs. non-ovarian). Key inclusion criteria are histologically proven recurrent or persistent clear cell carcinoma of the ovary, endometrium, cervix, vagina, or vulva; up to five prior lines of therapy; disease progression within 12 months after platinumbased chemotherapy; and measurable disease. Key exclusion criteria are prior treatment with an anti–PD-1, anti–programmed death-ligand 1, or anti–programmed death-ligand 2 agent.The primary endpoint is progression-free survival determined by investigators. Secondary endpoints are ORR, disease control rate, clinical benefit rate, progression-free survival 2, overall survival, and toxicity. Exploratory objectives include immune biomarkers.

INTRODUCTION: We aimed to compare the real-world data and our clinical experience with metallic stents (MSs) and conventional polymeric stents (PSs) in the management of both malignant and benign chronic ureteric obstruction (CUO), in terms of clinical outcomes and costs. METHODS: Clinical data from our institution, including outcomes for all ureteric stents inserted for long-term management of CUO from all causes from 2014 to 2017, were retrospectively reviewed and compared between the MS and PS episodes. RESULTS: A total of 247 stents were placed in 63 patients with CUO over the 4-year study period. Of these, 45 stents were MSs. There was no significant difference in all baseline characteristics between the MS and PS groups, except for the aetiology of obstructive cause. Mean indwelling stent duration was significantly greater for MS than for PS (228.6 ± 147.0 vs. 146.1 ± 66.0 days, P < 0.001), thereby leading to lower average number of stent changes per year in the MS group compared to the PS group (1.4 vs. 6.3 times, respectively). Despite the higher unit cost of MS compared to PS, there was no significant mean cost difference overall (cost per dwelling day SGD 7.82 ± SGD 10.44 vs. SGD 8.23 ± SGD 20.50, P = 0.888). CONCLUSION Resonance MS is a better option than PS to manage CUO from malignant and benign causes because its significantly longer indwelling time mitigates the higher unit cost of the stent. It potentially reduces the number of procedures and operations in patients. Thus, it should be considered for all patients with CUO requiring long-term ureteric drainage.
Humans ; Ureteral Obstruction/economics* ; Female ; Male ; Retrospective Studies ; Stents/economics* ; Middle Aged ; Aged ; Treatment Outcome ; Chronic Disease ; Ureter/surgery* ; Metals ; Adult ; Aged, 80 and over

BACKGROUND: The FAVOR (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease) III China trial demonstrated that percutaneous coronary intervention (PCI) lesion selection using quantitative flow ratio (QFR) measurement, a novel angiography-based approach for estimating fractional flow reserve, improved two-year clinical outcomes compared with standard angiography guidance. This study aimed to assess the cost-effectiveness of QFR-guided PCI from the perspective of the current Chinese healthcare system. METHODS: This study is a pre-specified analysis of the FAVOR III China trial, which included 3825 patients randomized between December 25, 2018, and January 19, 2020, from 26 centers in China. Patients with stable or unstable angina pectoris or those ≥72 hours post-myocardial infarction who had at least one lesion with a diameter stenosis between 50% and 90% in a coronary artery with a ≥2.5 mm reference vessel diameter by visual assessment were randomized to a QFR-guided strategy or an angiography-guided strategy with 1:1 ratio. During the two-year follow-up, data were collected on clinical outcomes, quality-adjusted life-years (QALYs), estimated costs of index procedure hospitalization, outpatient cardiovascular medication use, and rehospitalization due to major adverse cardiac and cerebrovascular events (MACCE). The primary analysis calculated the incremental cost-effectiveness ratio (ICER) as the cost per MACCE avoided. An ICER of ¥10,000/MACCE event avoided was considered economically attractive in China. RESULTS: At two years, the QFR-guided group demonstrated a reduced rate of MACCE compared to the angiography-guided group (10.8% vs . 14.7%, P <0.01). Total two-year costs were similar between the groups (¥50,803 ± 21,121 vs . ¥50,685 ± 23,495, P = 0.87). The ICER for the QFR-guided strategy was ¥3055 per MACCE avoided, and the probability of QFR being economically attractive was 64% at a willingness-to-pay threshold of ¥10,000/MACCE avoided. Sensitivity analysis showed that QFR-guided PCI would become cost-saving if the cost of QFR were below ¥3682 (current cost: ¥3800). Cost-utility analysis yielded an ICER of ¥56,163 per QALY gained, with a 53% probability of being cost-effective at a willingness-to-pay threshold of ¥85,000 per QALY gained. CONCLUSION: In patients undergoing PCI, a QFR-guided strategy appears economically attractive compared to angiographic guidance from the perspective of the Chinese healthcare system. TRIAL REGISTRATION ClinicalTrials.gov , NCT03656848.
Humans ; Cost-Benefit Analysis ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Angiography/methods* ; Middle Aged ; Aged ; Coronary Artery Disease/surgery* ; Quality-Adjusted Life Years ; Fractional Flow Reserve, Myocardial/physiology*

OBJECTIVES

While the chronically overburdened state of public school teachers in the Philippines is well-established, little is known about how they specifically provide ‘care’ and attend to their students’ health in the workplace. This article addresses that knowledge gap by illustrating the many forms of ‘health work’ undertaken by public school teachers on a daily basis, and analyzing the concrete challenges they face in doing such work. In so doing, this article provides a qualitative construction of school teachers as ‘health workers’ in the country.

This article draws from two focus group discussions conducted in Southern Luzon and Eastern Visayas between November 2018 to May 2019, as part of a multi-sited study on the health-related challenges faced by lowand middle-income Filipinos. A total of 19 teachers participated in those two discussions. We used the principles of thematic analysis to code and analyze the discussion transcripts.

Teachers regularly fulfill various tasks that can be considered health work, including measuring students’ anthropometrics; supervising and administering government programs like deworming, feeding programs, and vaccinations; providing first-aid and various forms of immediate medical attention; addressing students’ mental and psychological health concerns; and working with students’ families in ways that resemble social work. However, the study participants largely considered themselves unqualified to do health work, often sacrificed their own personal health and interpersonal relationships to take on the additional burden of health work, and felt they received insufficient institutional support.

Doing health work not only takes away from actual teaching time, but also comes at the expense of teachers’ own health. Hiring the appropriate personnel to conduct health work and improving legal safeguards are possible solutions to ameliorating the present working conditions of teachers. Yet, the larger and more long-term conversation demands the prioritiziation of teachers’ well-being and overall quality of life, and recognizing the cruciality of a healthy work-life balance for them. Future studies should involve more diverse geographic sites and teacher populations, and utilize more focused forms of analysis (e.g., comparative, policy-driven).

Background: We evaluated changes in glycemic status, over 1 year, of coronavirus disease 2019 (COVID-19) survivors with dysglycemia in acute COVID-19. Methods: COVID-19 survivors who had dysglycemia (defined by glycosylated hemoglobin [HbA1c] 5.7% to 6.4% or random glucose ≥10.0 mmol/L) in acute COVID-19 were recruited from a major COVID-19 treatment center from September to October 2020. Matched non-COVID controls were recruited from community. The 75-g oral glucose tolerance test (OGTT) were performed at baseline (6 weeks after acute COVID-19) and 1 year after acute COVID-19, with HbA1c, insulin and C-peptide measurements. Progression in glycemic status was defined by progression from normoglycemia to prediabetes/diabetes, or prediabetes to diabetes. Results: Fifty-two COVID-19 survivors were recruited. Compared with non-COVID controls, they had higher C-peptide (P< 0.001) and trend towards higher homeostasis model assessment of insulin resistance (P=0.065). Forty-three COVID-19 survivors attended 1-year reassessment. HbA1c increased from 5.5%±0.3% to 5.7%±0.2% (P<0.001), with increases in glucose on OGTT at fasting (P=0.089), 30-minute (P=0.126), 1-hour (P=0.014), and 2-hour (P=0.165). At baseline, 19 subjects had normoglycemia, 23 had prediabetes, and one had diabetes. Over 1 year, 10 subjects (23.8%; of 42 non-diabetes subjects at baseline) had progression in glycemic status. C-peptide levels remained unchanged (P=0.835). Matsuda index decreased (P=0.007) and there was a trend of body mass index increase from 24.4±2.7 kg/m2 to 25.6±5.2 (P=0.083). Subjects with progression in glycemic status had more severe COVID-19 illness than non-progressors (P=0.030). Reassessment was not performed in the control group. Conclusion Subjects who had dysglycemia in acute COVID-19 were characterized by insulin resistance. Over 1 year, a quarter had progression in glycemic status, especially those with more severe COVID-19. Importantly, there was no significant deterioration in insulin secretory capacity.

Purpose: Patients with cancer are particularly vulnerable to coronavirus disease (COVID). Transportation barriers made travel to obtain medical care more difficult during the pandemic. Whether these factors led to changes in the distance traveled for radiotherapy and the coordinated location of radiation treatment is unknown. Materials and Methods: We analyzed patients across 60 cancer sites in the National Cancer Database from 2018 to 2020. Demographic and clinical variables were analyzed for changes in distance traveled for radiotherapy. We designated the facilities in the 99th percentile or above in terms of the proportion of patients who traveled more than 200 miles as “destination facilities.” We defined “coordinated care” as undergoing radiotherapy at the same facility where the cancer was diagnosed. Results: We evaluated 1,151,954 patients. There was a greater than 1% decrease in the proportion of patients treated in the Mid-Atlantic States. Mean distance traveled from place of residence to radiation treatment decreased from 28.6 to 25.9 miles, and the proportion traveling greater than 50 miles decreased from 7.7% to 7.1%. At “destination facilities,” the proportion traveling more than 200 miles decreased from 29.3% in 2018 to 24% in 2020. In comparison, at the other hospitals, the proportion traveling more than 200 miles decreased from 1.07% to 0.97%. In 2020, residing in a rural area resulted in a lower odds of having coordinated care (multivariable odds ratio = 0.89; 95% confidence interval, 0.83–0.95). Conclusion The first year of the COVID pandemic measurably impacted the location of U.S. radiation therapy treatment.

Problem: Emergency medical teams (EMTs) deployed to mass casualty incidents (MCIs) are required to work outside their usual settings and according to different principles, which may affect their performance and the survival of casualties. Prior to 2013, training offered to domestic EMTs was limited to ad hoc and infrequent simulation exercises. Context: Domestic EMTs are activated from public tertiary hospitals to provide pre-hospital medical support to the Singapore Civil Defence Force and establish a first-aid post (FAP) for triaging, stabilizing and treating casualties. These casualties are then evacuated to public hospitals for further management. Action: Recognizing the need for a more systematic approach to the training of domestic EMTs, the Disaster Medical Responder’s Course (the Course) was developed as a multi-institutional collaboration to equip EMT members attending a MCI with the necessary skills to perform effectively at the FAP. Outcome: The Course was first run in 2013 and is usually offered six to eight times a year. Since June 2019, a total of 414 health-care staff and allied health professionals have participated. There have been numerous revisions of the course content and delivery to reflect the latest concepts in operations and global best practice, as well as developments in educational methodologies. Discussion: Preparedness is crucial to optimize the survival and outcomes of casualties. The Course provides standardized training of domestic EMTs and plays a pivotal role in ensuring operational readiness for MCIs in Singapore.

Alzheimer's disease （AD） is a deleterious neurodegenerative disorder， which has become a significant public health concern and economic burden. The pathogenesis of AD is complex and involves several hypotheses such as amyloid β-protein （Aβ） deposition， Tau protein hyperphosphorylation， oxidative stress， and inflammation. There is an urgent need for a holism-based comprehensive intervention with multi-pathway， multi-level， and multi-target characteristics， which demonstrates the unique advantage of traditional Chinese medicine （TCM）. Therefore， it is of great significance to conduct and promote research on TCM treatment of AD. Danggui Shaoyaosan （DSS） from the Synopsis of Golden Chamber （《金匮要略》） by ZHANG Zhongjing （150 AD-219 AD） was originally designed for reliving gynecological ailments. It is a classic TCM formula that modulates liver and spleen and dispels blood stasis and water retention. Since the late 1980s when Japanese researchers reported its therapeutic effect on AD， it has been widely used in the clinic with clear effects. The elucidation of the mechanism of this formula helps exert its effects. Hereby， this paper reviewed relative research progress and made an analysis in terms of attenuating aberrant accumulation of Aβ and hyperphosphorylated Tau protein， anti-inflammatory and antioxidant activities， mediating neurotransmitters， ameliorating lipid metabolism， modulating gut microbiota， reduced neuron apoptosis， decreasing intracellular Ca²⁺ overloading， and increasing the expression of estradiol. This paper is expected to provide references for understanding the scientific connotation of DDS in the treatment of AD and lay a solid foundation for further investigation.