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: Outcomes after SARS-CoV-2 Omicron infection in patients with heart failure (HF) and ischaemic heart disease (IHD) remain poorly defined. METHOD: In a highly vaccinated cohort of adult Singapore citizens and permanent residents, we used Cox proportional hazards models (adjusted for sociodemographic variables and comorbidities) to compare the risks of Omicron infection, COVID-19- related hospitalisation, and severe COVID-19 between indivi-duals with HF or IHD and matched controls without these conditions. RESULTS: From national databases, we identified 15,426 HF patients matched 1:∼3 to 41,221 controls, and 110,442 IHD patients matched 1:∼2 to 223,843 controls. Over 80% of HF and IHD patients had received at least 3 vaccine doses. During the Omicron-predominant period, both HF and IHD cohorts demonstrated higher adjusted risks of COVID-19 hospitalisation compared with matched controls (HF: adjusted hazard ratio [aHR] 1.77, 95% confidence interval [CI] 1.65-1.90; IHD: aHR 1.21, 95% CI 1.17-1.26). Among those with at least 1 HF-or IHD-related admission in the prior year, hospitalisation risk was further elevated (HF: aHR 1.27, 95% CI 1.13-1.42; IHD: aHR 1.11, 95% CI 1.01-1.23). Receipt of ≥3 vaccine doses was associated with substantially lower risk of severe COVID-19 versus only 2 doses (HF: aHR 0.35, 95% CI 0.28-0.43; IHD: aHR 0.27, 95% CI 0.23-0.32). A fourth dose conferred additional reductions in infection and adverse outcomes, though CIs for infection overlapped with those for 3 doses. CONCLUSION During Omicron predominance, HF and IHD patients experienced greater risk of COVID-19 hospitalisation and severe COVID-19 versus matched controls. Booster vaccinations attenuated these risks. Individuals with recent HF/IHD admissions should be prioritised for receipt of booster vaccine doses.
Humans ; COVID-19/complications* ; Male ; Heart Failure/complications* ; Myocardial Ischemia/complications* ; Female ; Middle Aged ; Hospitalization/statistics & numerical data* ; Aged ; COVID-19 Vaccines/administration & dosage* ; Singapore/epidemiology* ; SARS-CoV-2 ; Proportional Hazards Models ; Adult ; Case-Control Studies ; Vaccination/statistics & numerical data*

INTRODUCTION: Obstructive sleep apnoea (OSA) is common in Singapore, with moderate to severe OSA affecting around 30% of residents. These consensus statements aim to provide scientifically grounded recommendations for the management of OSA, standar-dise the management of OSA in Singapore and promote multidisciplinary collaboration. METHOD: An expert panel, which was convened in 2024, identified several areas of OSA management that require guidance. The expert panel reviewed the current literature and developed consensus statements, which were later independently voted on using a 3-point Likert scale (agree, neutral or disagree). Consensus (total ratings of agree and neutral) was set a priori at ≥80% agreement. Any statement not reaching consensus was excluded. RESULTS: The final consensus included 49 statements that provide guidance on the screening, diagnosis and management of adults with OSA. Additionally, 23 statements on the screening, diagnosis and management of paediatric OSA achieved consensus. These 72 consensus statements considered not only the latest clinical evidence but also the benefits and harms, resource implications, feasibility, acceptability and equity impact of the recommendations. CONCLUSION The statements presented in this paper aim to guide clinicians based on the most updated evidence and collective expert opinion from sleep specialists in Singapore. These recommendations should augment clinical judgement rather than replace it. Management decisions should be individualised, taking into account the patient's clinical characteristics, as well as patient and caregiver concerns and preferences.
Humans ; Sleep Apnea, Obstructive/diagnosis* ; Singapore ; Consensus ; Adult

Problem: Emergency medical teams (EMTs) responding to mass casualty incidents attend to casualties in a chaotic, high-pressure and resource-limited environment that is vastly different from their day-to-day work. The nature of mass casualty incidents and the work environment can impact psychological resilience, but the psychological resilience of members of EMTs has not been evaluated. Context: In Singapore, EMTs are deployed from public hospitals, polyclinics and the Singapore Red Cross to disaster sites, where they triage, stabilize and treat casualties before evacuating them to public hospitals for further management. Action: Twenty-four members of EMTs responded to a cross-sectional survey based on a psychological resilience tool developed for health-care rescuers involved in mass casualty incidents to evaluate their psychological resilience after a full-scale exercise involving an aviation accident. Respondents completed a psychological resilience tool that was developed by experts in disaster work and research using a modified Delphi approach. There were 27 items across eight domains: optimism, altruism, preparations for disaster rescue, social support, perceived control, self-efficacy, coping strategies and positive growth. Outcome: The key observations from the survey were that (i) staff demonstrated a strong sense of altruism and had good social support; (ii) staff were not confident about their preparedness, and this led to a lack of optimism, perceived control and ability to deal with emotions; and (iii) it was necessary for respondents to reflect on their experience to find meaning to support growth after the deployment. Discussion: Optimizing casualty survival and outcomes during mass casualty incidents requires not only excellent procedural training and robust standard operating procedures and work processes but also dedicated efforts to enhance the psychological resilience of members of EMTs.

BACKGROUND Hypertension is the most common risk factor for cardiovascular disease in the Philippines. Despite the availability of antihypertensive medications that are effective, safe, and tolerated by Filipino patients, the numbers of uncontrolled hypertensives are still increasing. Several factors play in the poor control of blood pressure, particularly resistant hypertension and hyperactive sympathetic nervous system. Renal denervation therapy is a novel device that has been shown to lower blood pressure in patients with resistant and difficult-to-treat hypertension and is deemed safe in clinical trials. A Philippine Working Group composed of specialists in cardiology, hypertension, vascular surgery, and clinical epidemiology has come up with consensus statements in identifying patients who will benefit from the procedure. Locally, there is a need to have hypertension centers treating uncontrolled and resistant hypertension and offer renal denervation therapy to appropriate Filipino patients.
Blood Pressure

Introduction: Social media has become a ubiquitous part of daily life. However, little is known about the influence of food-related social media content (FRSMC) on the eating habits of Malaysian undergraduates. This study explored FRSMC usage of undergraduates enrolled in a non-health program, its influence on eating habits, and how such social media content influences dietary behaviours. Method: This qualitative semi-structured interview study involved chemical engineering (CE) undergraduates at a university in Penang, Malaysia. The study was carried out from April 2021 to March 2022 during which ten participants were purposively selected. Based on precedent qualitative research sampling rule of thumb, this sample size of ten participants provided sufficient data saturation for an initial exploratory study. The interview sessions were recorded, transcribed, and thematically analyzed. Results: According to study findings, in terms of usage, food advertising and promotions; cooking tutorials and food and nutrition information are the most appealing types of FRSMC. With regards to eating habits, FRSMC can lead to healthy and unhealthy food choices. The study identified several perceived challenges, namely unrealistic and untrustworthy content, difficult and repetitive content, and algorithm-driven deviations from healthy diets. The effectiveness of FRSMC can be enhanced by creating trustworthy and engaging content. Conclusion: The study highlights that social media engagement can have both positive and negative impact on food choices among undergraduates. Some FRSMC are perceived to encourage and motivate undergraduates to adopt healthier dietary habits. Future research could involve a larger sample, representative of diverse socio-demographic groups in Malaysia.

BACKGROUND

Coronavirus disease 2019 (COVID-19) has been associated with acute liver injury presenting as increased liver enzymes, specifically alanine aminotransferase (ALT) and aspartate aminotransferase (AST). There is limited data in the prevalence of liver injury in COVID 19. We aim to determine the prevalence of acute liver injury among COVID-19 patients admitted in a tertiary hospital in the Philippines.

The study is a single center, retrospective cohort of all COVID-19 patients with baseline AST and ALT admitted at St. Luke’s Medical Center - Quezon City from January 2020 to December 2021. The population was divided into those with normal liver enzymes, mild (AST and/or ALT 1-3 times ULN), and severe (AST and/or ALT >3x ULN) acute liver injury. Association of liver injury to clinical outcome, COVID 19 disease severity, and length of hospital stay were determined. Among those with elevated AST/ALT, comparison of the levels before and after treatment with hepatoprotective agents were evaluated.

Among the 669 patients included in the analysis, 448 (67%) developed liver injury of which 50 (7.5%) had severe liver injury and 398 (59.5%) developed mild liver injury. Chi squared analysis showed that acute liver injury (OR:2.64,CI:1.90-3.69, p < 0.01) was associated with COVID-19 severity. However, acute liver injury was not associated with clinical outcome (p = 0.347) and length of hospital stay (p = 0.317). There was no association between the use of hepatoprotective agents and changes in level of transaminases (p=0.087).

This study revealed that mild liver injury is commonly found in patients with COVID-19 infection. Severity of liver injury is significantly associated with COVID-19 severity, but not with clinical outcome and length of hospital stay. In this study, treatment with hepatoprotective agents did not lead to a decrease in liver enzymes. Further evaluation is needed to recognize those patients at higher risk of complications and identify effective therapies in providing better clinical outcomes.