1.Extrapulmonary manifestations and complications of severe acute respiratory syndrome coronavirus-2 infection: a systematic review.
Jiacai CHO ; Joanne LEE ; Ching-Hui SIA ; Chieh Sian KOO ; Benjamin Y Q TAN ; Weizhen HONG ; Ellie CHOI ; Xueying GOH ; Louis CHAI ; Nisha Suyien CHANDRAN ; Horng Ruey CHUA ; Bernard P L CHAN ; Mark MUTHIAH ; Ting Ting LOW ; Eng Soo YAP ; Manjari LAHIRI
Singapore medical journal 2023;64(6):349-365
		                        		
		                        			INTRODUCTION:
		                        			We aimed to describe the extrapulmonary manifestations of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, including their frequency, onset with respect to respiratory symptoms, pathogenesis and association with disease severity.
		                        		
		                        			METHODS:
		                        			We searched the MEDLINE and Embase databases for SARS-CoV-2-related studies. Meta-analysis, observational studies, case series and case reports published in English or Chinese between 1 January 2020 and 1 May 2020 were included. Reports with only paediatric or obstetric cases were excluded.
		                        		
		                        			RESULTS:
		                        			169 articles were included. Early manifestations (preceding respiratory symptoms until Day 6 of onset) included olfactory and gustatory disturbance (self-reported in up to 68% and 85% of cases, respectively), gastrointestinal symptoms (up to 65.9%) and rash (up to 20.4%). From Day 7 onwards, hypercytokinaemia, paralleled multi-organ complications including acute cardiac injury (pooled incidence of 17.7% in 1,412 patients, mostly with severe disease and 17.4% mortality), kidney and liver injury (up to 17% and 33%, respectively) and thrombocytopenia (up to 30%). Hypercoagulability resulted in venous thromboembolic events in up to 31% of all patients. Uncommon disease presentation and complications comprised Guillain-Barré syndrome, rhabdomyolysis, otitis media, meningoencephalitis and spontaneous pneumomediastinum.
		                        		
		                        			CONCLUSION
		                        			Although the systemic manifestations of SARS-CoV-2 infection are variegated, they are deeply interwoven by shared mechanisms. Two phases of extrapulmonary disease were identified: (a) an early phase with possible gastrointestinal, ocular and cutaneous involvement; and (b) a late phase characterised by multiorgan dysfunction and clinical deterioration. A clear, multidisciplinary consensus to define and approach thromboinflammation and cytokine release syndrome in SARS-CoV-2 is needed.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Asian People
		                        			;
		                        		
		                        			COVID-19/complications*
		                        			;
		                        		
		                        			Inflammation/complications*
		                        			;
		                        		
		                        			SARS-CoV-2
		                        			;
		                        		
		                        			Thrombosis
		                        			
		                        		
		                        	
2.The impact of obesity: a narrative review.
Benjamin Chih Chiang LAM ; Amanda Yuan Ling LIM ; Soo Ling CHAN ; Mabel Po Shan YUM ; Natalie Si Ya KOH ; Eric Andrew FINKELSTEIN
Singapore medical journal 2023;64(3):163-171
		                        		
		                        			
		                        			Obesity is a disease with a major negative impact on human health. However, people with obesity may not perceive their weight to be a significant problem and less than half of patients with obesity are advised by their physicians to lose weight. The purpose of this review is to highlight the importance of managing overweight and obesity by discussing the adverse consequences and impact of obesity. In summary, obesity is strongly related to >50 medical conditions, with many of them having evidence from Mendelian randomisation studies to support causality. The clinical, social and economic burdens of obesity are considerable, with these burdens potentially impacting future generations as well. This review highlights the adverse health and economic consequences of obesity and the importance of an urgent and concerted effort towards the prevention and management of obesity to reduce the burden of obesity.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Obesity
		                        			;
		                        		
		                        			Overweight
		                        			;
		                        		
		                        			Physicians
		                        			
		                        		
		                        	
3.Clinical efficacy and long-term immunogenicity of an early triple dose regimen of SARS-CoV-2 mRNA vaccination in cancer patients.
Matilda Xinwei LEE ; Siyu PENG ; Ainsley Ryan Yan Bin LEE ; Shi Yin WONG ; Ryan Yong Kiat TAY ; Jiaqi LI ; Areeba TARIQ ; Claire Xin Yi GOH ; Ying Kiat TAN ; Benjamin Kye Jyn TAN ; Chong Boon TEO ; Esther CHAN ; Melissa OOI ; Wee Joo CHNG ; Cheng Ean CHEE ; Carol L F HO ; Robert John WALSH ; Maggie WONG ; Yan SU ; Lezhava ALEXANDER ; Sunil Kumar SETHI ; Shaun Shi Yan TAN ; Yiong Huak CHAN ; Kelvin Bryan TAN ; Soo Chin LEE ; Louis Yi Ann CHAI ; Raghav SUNDAR
Annals of the Academy of Medicine, Singapore 2023;52(1):8-16
		                        		
		                        			INTRODUCTION:
		                        			Three doses of SARS-CoV-2 mRNA vaccines have been recommended for cancer patients to reduce the risk of severe disease. Anti-neoplastic treatment, such as chemotherapy, may affect long-term vaccine immunogenicity.
		                        		
		                        			METHOD:
		                        			Patients with solid or haematological cancer were recruited from 2 hospitals between July 2021 and March 2022. Humoral response was evaluated using GenScript cPASS surrogate virus neutralisation assays. Clinical outcomes were obtained from medical records and national mandatory-reporting databases.
		                        		
		                        			RESULTS:
		                        			A total of 273 patients were recruited, with 40 having haematological malignancies and the rest solid tumours. Among the participants, 204 (74.7%) were receiving active cancer therapy, including 98 (35.9%) undergoing systemic chemotherapy and the rest targeted therapy or immunotherapy. All patients were seronegative at baseline. Seroconversion rates after receiving 1, 2 and 3 doses of SARS-CoV-2 mRNA vaccination were 35.2%, 79.4% and 92.4%, respectively. After 3 doses, patients on active treatment for haematological malignancies had lower antibodies (57.3%±46.2) when compared to patients on immunotherapy (94.1%±9.56, P<0.05) and chemotherapy (92.8%±18.1, P<0.05). SARS-CoV-2 infection was reported in 77 (28.2%) patients, of which 18 were severe. No patient receiving a third dose within 90 days of the second dose experienced severe infection.
		                        		
		                        			CONCLUSION
		                        			This study demonstrates the benefit of early administration of the third dose among cancer patients.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			SARS-CoV-2
		                        			;
		                        		
		                        			COVID-19/prevention & control*
		                        			;
		                        		
		                        			Treatment Outcome
		                        			;
		                        		
		                        			Neoplasms/drug therapy*
		                        			;
		                        		
		                        			Hematologic Neoplasms
		                        			;
		                        		
		                        			Vaccination
		                        			;
		                        		
		                        			RNA, Messenger
		                        			;
		                        		
		                        			Antibodies, Viral
		                        			;
		                        		
		                        			Immunogenicity, Vaccine
		                        			
		                        		
		                        	
4.Safety attitudes, burnout and well-being among healthcare workers during the COVID-19 pandemic: an Indo-Pacific regional cross-sectional study.
Abhiram KANNEGANTI ; Benjamin Yong Qiang TAN ; Nik Hisamuddin NIK AB RAHMAN ; Aloysius Sheng-Ting LEOW ; Max DENNING ; Ee Teng GOH ; Lucas Jun HAO LIM ; Ching-Hui SIA ; Ying Xian CHUA ; James KINROSS ; Melanie TAN ; Li Feng TAN ; Yi Min WAN ; Arvind SHARMA ; Rivan DANUAJI ; R N KOMAL KUMAR ; Chew Keng SHENG ; Cheah Phee KHENG ; Sarah Shaikh ABDUL KARIM ; Mohd Najib ABDUL GHANI ; Suhaimi MAHMUD ; Yiong Huak CHAN ; Vijay Kumar SHARMA ; Kang SIM ; Shirley Beng SUAT OOI
Singapore medical journal 2023;64(11):667-676
		                        		
		                        			INTRODUCTION:
		                        			The coronavirus disease 2019 (COVID-19) pandemic has had an unprecedented impact in Asia and has placed significant burden on already stretched healthcare systems. We examined the impact of COVID-19 on the safety attitudes among healthcare workers (HCWs), as well as their associated demographic and occupational factors, and measures of burnout, depression and anxiety.
		                        		
		                        			METHODS:
		                        			A cross-sectional survey study utilising snowball sampling was performed involving doctors, nurses and allied health professions from 23 hospitals in Singapore, Malaysia, India and Indonesia between 29 May 2020 and 13 July 2020. This survey collated demographic data and workplace conditions and included three validated questionnaires: the Safety Attitudes Questionnaire (SAQ), Oldenburg Burnout Inventory and Hospital Anxiety and Depression Scale. We performed multivariate mixed-model regression to assess independent associations with the SAQ total percentage agree rate (PAR).
		                        		
		                        			RESULTS:
		                        			We obtained 3,163 responses. The SAQ total PARs were found to be 35.7%, 15.0%, 51.0% and 3.3% among the respondents from Singapore, Malaysia, India and Indonesia, respectively. Burnout scores were highest among respondents from Indonesia and lowest among respondents from India (70.9%-85.4% vs. 56.3%-63.6%, respectively). Multivariate analyses revealed that meeting burnout and depression thresholds and shifts lasting ≥12 h were significantly associated with lower SAQ total PAR.
		                        		
		                        			CONCLUSION
		                        			Addressing the factors contributing to high burnout and depression and placing strict limits on work hours per shift may contribute significantly towards improving safety culture among HCWs and should remain priorities during the pandemic.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Cross-Sectional Studies
		                        			;
		                        		
		                        			Pandemics
		                        			;
		                        		
		                        			COVID-19/epidemiology*
		                        			;
		                        		
		                        			Burnout, Psychological
		                        			;
		                        		
		                        			Health Personnel
		                        			
		                        		
		                        	
5.Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratios Are Associated with Recurrent Ischemic Stroke in Patients with Embolic Stroke of Undetermined Source
Tony Y.W. LI ; Ching-Hui SIA ; Bernard P.L. CHAN ; Jamie S.Y. HO ; Aloysius S. LEOW ; Mark Y. CHAN ; Pipin KOJODJOJO ; Mary Joyce GALUPO ; Hock-Luen TEOH ; Vijay K. SHARMA ; Raymond C.S. SEET ; Leonard L.L. YEO ; Benjamin Yong-Qiang TAN
Journal of Stroke 2022;24(3):421-424
		                        		
		                        		
		                        		
		                        	
7.Non-alcoholic fatty liver disease increases risk of carotid atherosclerosis and ischemic stroke: An updated meta-analysis with 135,602 individuals
Ansel Shao Pin TANG ; Kai En CHAN ; Jingxuan QUEK ; Jieling XIAO ; Phoebe TAY ; Margaret TENG ; Keng Siang LEE ; Snow Yunni LIN ; May Zin MYINT ; Benjamin TAN ; Vijay K SHARMA ; Darren Jun Hao TAN ; Wen Hui LIM ; Apichat KAEWDECH ; Daniel HUANG ; Nicholas WS CHEW ; Mohammad Shadab SIDDIQUI ; Arun J SANYAL ; Mark MUTHIAH ; Cheng Han NG
Clinical and Molecular Hepatology 2022;28(3):483-496
		                        		
		                        			 Background/Aims:
		                        			Non-alcoholic fatty liver disease (NAFLD) is associated with the development of cardiovascular disease. While existing studies have examined cardiac remodeling in NAFLD, there has been less emphasis on the development of carotid atherosclerosis and stroke. We sought to conduct a meta-analysis to quantify the prevalence, risk factors, and degree of risk increment of carotid atherosclerosis and stroke in NAFLD. 
		                        		
		                        			Methods:
		                        			Embase and Medline were searched for articles relating to NAFLD, carotid atherosclerosis, and stroke. Proportional data was analysed using a generalized linear mixed model. Pairwise meta-analysis was conducted to obtain odds ratio or weighted mean difference for comparison between patients with and without NAFLD. 
		                        		
		                        			Results:
		                        			From pooled analysis of 30 studies involving 7,951 patients with NAFLD, 35.02% (95% confidence interval [CI], 27.36–43.53%) had carotid atherosclerosis with an odds ratio of 3.20 (95% CI, 2.37–4.32; P<0.0001). Pooled analysis of 25,839 patients with NAFLD found the prevalence of stroke to be 5.04% (95% CI, 2.74–9.09%) with an odds ratio of 1.88 (95% CI, 1.23–2.88; P=0.02) compared to non-NAFLD. The degree of steatosis assessed by ultrasonography in NAFLD was closely associated with risk of carotid atherosclerosis and stroke. Older age significantly increased the risk of developing carotid atherosclerosis, but not stroke in NAFLD. 
		                        		
		                        			Conclusions
		                        			This meta-analysis shows that a stepwise increment of steatosis of NAFLD can significantly increase the risk of carotid atherosclerosis and stroke development in NAFLD. Patients more than a third sufferred from carotid atherosclerosis and routine assessment of carotid atherosclerosis is quintessential in NAFLD. 
		                        		
		                        		
		                        		
		                        	
8.Treating acutely ill patients at home: Data from Singapore.
Stephanie Q KO ; Joel GOH ; Yee Kian TAY ; Norshima NASHI ; Benjamin M Y HOOI ; Nan LUO ; Win Sen KUAN ; John T Y SOONG ; Derek CHAN ; Yi Feng LAI ; Yee Wei LIM
Annals of the Academy of Medicine, Singapore 2022;51(7):392-399
		                        		
		                        			INTRODUCTION:
		                        			Hospital-at-home programmes are well described in the literature but not in Asia. We describe a home-based inpatient substitutive care programme in Singapore, with clinical and patient-reported outcomes.
		                        		
		                        			METHODS:
		                        			We conducted a retrospective cohort study of patients admitted to a hospital-at-home programme from September 2020 to September 2021. Suitable patients, who otherwise required hospitalisation, were admitted to the programme. They were from inpatient wards, emergency department and community nursing teams in the western part of Singapore, where a multidisciplinary team provided hospital-level care at home. Electronic health record data were extracted from all patients admitted to the programme. Patient satisfaction surveys were conducted post-discharge.
		                        		
		                        			RESULTS:
		                        			A total of 108 patients enrolled. Mean age was 67.9 (standard deviation 16.7) years, and 46% were male. The main diagnoses were skin and soft tissue infections (35%), urinary tract infections (29%) and fluid overload (18%). Median length of stay was 4 (interquartile range 3-7) days. Seven patients were escalated back to the hospital, of whom 2 died after escalation. One patient died at home. There was 1 case of adverse drug reaction and 1 fall at home, and no cases of hospital-acquired infections. Patient satisfaction rates were high and 94% of contactable patients would choose to participate again.
		                        		
		                        			CONCLUSION
		                        			Hospital-at-home programmes appear to be safe and feasible alternatives to inpatient care in Singapore. Further studies are warranted to compare clinical outcomes and cost to conventional inpatient care.
		                        		
		                        		
		                        		
		                        			Aftercare
		                        			;
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Hospitalization
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Length of Stay
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Patient Discharge
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Singapore
		                        			
		                        		
		                        	
9.Impact of COVID-19 infections among kidney transplant recipients.
Shimin Jasmine CHUNG ; Quan Yao HO ; Ian Tatt LIEW ; Siew Yee THIEN ; Yvonne Fu Zi CHAN ; Benjamin Pei Zhi CHERNG ; Hei Man WONG ; Ying Ying CHUA ; Terence KEE ; Thuan Tong TAN
Annals of the Academy of Medicine, Singapore 2022;51(2):122-126
10.Bridging Thrombolysis versus Direct Mechanical Thrombectomy in Stroke Due to Basilar Artery Occlusion
Isabel SIOW ; Benjamin Y.Q. TAN ; Keng Siang LEE ; Natalie ONG ; Emma TOH ; Anil GOPINATHAN ; Cunli YANG ; Pervinder BHOGAL ; Erika LAM ; Oliver SPOONER ; Lukas MEYER ; Jens FIEHLER ; Panagiotis PAPANAGIOTOU ; Andreas KASTRUP ; Maria ALEXANDROU ; Seraphine ZUBEL ; Qingyu WU ; Anastasios MPOTSARIS ; Volker MAUS ; Tommy ANDERSON ; Vamsi GONTU ; Fabian ARNBERG ; Tsong Hai LEE ; Bernard P.L. CHAN ; Raymond C.S. SEET ; Hock Luen TEOH ; Vijay K. SHARMA ; Leonard L.L. YEO
Journal of Stroke 2022;24(1):128-137
		                        		
		                        			 Background:
		                        			and Purpose Mechanical thrombectomy (MT) is an effective treatment for patients with basilar artery occlusion (BAO) acute ischemic stroke. It remains unclear whether bridging intravenous thrombolysis (IVT) prior to MT confers any benefit. This study compared the outcomes of acute BAO patients who were treated with direct MT versus combined IVT plus MT. 
		                        		
		                        			Methods:
		                        			This multicenter retrospective cohort study included patients who were treated for acute BAO from eight comprehensive stroke centers between January 2015 and December 2019. Patients received direct MT or combined bridging IVT plus MT. Primary outcome was favorable functional outcome defined as modified Rankin Scale 0–3 measured at 90 days. Secondary outcome measures included mortality and symptomatic intracranial hemorrhage (sICH). 
		                        		
		                        			Results:
		                        			Among 322 patients, 127 (39.4%) patients underwent bridging IVT followed by MT and 195 (60.6%) underwent direct MT. The mean±standard deviation age was 67.5±14.1 years, 64.0% were male and median National Institutes of Health Stroke Scale was 16 (interquartile range, 8 to 25). At 90-day, the rate of favorable functional outcome was similar between the bridging IVT and direct MT groups (39.4% vs. 34.4%, P=0.361). On multivariable analyses, bridging IVT was not asComorbidisociated with favorable functional outcome, mortality or sICH. In subgroup analyses, patients with underlying atherosclerosis treated with bridging IVT compared to direct MT had a higher rate of favorable functional outcome at 90 days (37.2% vs. 15.5%, P=0.013). 
		                        		
		                        			Conclusions
		                        			Functional outcomes were similar in BAO patients treated with bridging IVT versus direct MT. In the subgroup of patients with underlying large-artery atherosclerosis stroke mechanism, bridging IVT may potentially confer benefit and this warrants further investigation. 
		                        		
		                        		
		                        		
		                        	
            
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