1.Asia-Pacific consensus statement on medication-related osteonecrosis of the jaw in patients with osteoporosis
Akira TAGUCHI ; Daisuke INOUE ; Jin-Woo KIM ; Keskanya KESKANYA ; Wai Sin CHAN ; Hee Dong CHAE ; Chung-Hwan CHEN ; Ching-Lung CHEUNG ; Eddie Siu Lun CHOW ; Yoon-Sok CHUNG ; Linsey GANI ; Muhammad Kamil BIN HASSAN ; Unnop JAISAMRARN ; Chakorn VORAKULPIPAT ; Nutchada SRIYARANYA ; Aasis UNNANUNTANA ; Tanawat AMPHANSAP ; Seng Bin ANG ; Fen Lee HEW ; Julie LI-YU ; Terence Ong Ing WEI ; Jeyakantha JEYAKANTHA ; Mark Anthony SANDOVAL ; Thawee SONGPATANASILP ; Monica Therese CATING-CABRAL ; Thanut VALLEENUKUL ; Lalita WATTANACHANYA ; Chih-Hsing CHIH-HSING ; Weibo XIA ; Jawl-Shan HWANG ; Hiroshi HAGINO ; Natthinee CHARATCHAROENWITTHAYA
Osteoporosis and Sarcopenia 2026;12(1):1-17
A unified consensus statement on medication-related osteonecrosis of the jaw (MRONJ) has not yet been established among the Asian member countries or regions of the Asian Federation of Osteoporosis Societies (AFOS). This study aimed to develop a consensus on MRONJ in patients with osteoporosis across these countries and regions. In this study, the term “Asia-Pacific” refers specifically to the Asian member countries and regions of AFOS. A structured survey consisting of nine MRONJ-related questions was distributed across 10 countries and regions to assess the level of agreement and summarize regional perspectives. In addition, a manual literature review and voting were conducted to evaluate the current evidence on MRONJ. The key aspects of MRONJ, including definition, staging, diagnosis, pathogenesis, risk factors, management, and prevention, were generally consistent among the AFOS countries and regions. The annual incidence and incidence rate of MRONJ associated with low-dose antiresorptive therapy in patients with osteoporosis ranged from 0.025% to 0.136% and 21 to 283 cases per 100,000 person-years, respectively. However, evidence regarding the benefits of drug discontinuation before dental surgery, such as tooth extraction, remains insufficient. Large-scale, multinational studies across AFOS countries and regions are warranted to determine the incidence of MRONJ better and evaluate the impact of antiresorptive drug discontinuation before dental procedures. These findings may contribute to the devel opment of effective evidence-based strategies for preventing MRONJ in patients with osteoporosis.
2.Utility of Self-Rated vs. Informant-Rated Ascertain Dementia-8 for Detection of Early Cognitive Impairment: Experience of a “Real-World” Memory Clinic
Khin Khin WIN ; Justin CHEW ; Jun Pei LIM ; Esther HO ; Noorhazlina ALI ; Mark CHAN ; Wee Shiong LIM
Annals of Geriatric Medicine and Research 2026;30(1):109-119
Background:
The Ascertain Dementia 8-item Questionnaire (AD8) is a validated informant-based interview for early dementia detection. Research suggests the utility of self-rated AD8 to identify milder dementia forms in research settings. This study compares the factor structure, reliability, and diagnostic performance between AD8-Self and AD8-Informant for early cognitive impairment (ECI) in a clinical setting.
Methods:
Five hundreds fifteen patient-informant dyads (43 cognitively intact and 472 ECI) from a tertiary memory clinic completed both self-reported and informant AD8. We conducted exploratory factor analysis to determine the factor structure, Cronbach’s alpha for internal consistency, and receiver operating characteristic (ROC) curve analysis for ECI, including a subgroup analysis for mild cognitive impairment (MCI).
Results:
The mean age and education of ECI participants were 75.61 years (range, 51–95) and 5.6 years (range, 0–20), respectively, and 72.6 years (range, 51–89) and 6.8 years (range, 0–16) in the MCI subgroup. Unlike AD8-Informant’s one-factor structure, AD8-Self had a two-factor structure corresponding to memory and non-memory domains. AD8-Self demonstrated lower reliability (Cronbach’s alpha: ECI 0.666 vs. 0.764; MCI 0.663 vs. 0.709). In ECI, AD8-Informant (cutoff score ≥3) showed better diagnostic performance (sensitivity 89%, specificity 79%) than AD8-Self (cutoff score ≥4; sensitivity 27.1%, specificity 95.3%) (AUC 0.915 vs. 0.593; p<0.001). Similar results were found in MCI (sensitivity 64.7% vs. 26.5%; specificity 79.1% vs. 95.3%; AUC 0.745 vs. 0.600; p=0.002).
Conclusion
AD8-Self has a distinct factor structure, lower reliability, and inferior diagnostic performance compared to AD8-Informant for ECI/MCI detection. Our result do not support AD8-Self as a standalone tool for detecting ECI or MCI.
3.Omicron SARS-CoV-2 outcomes in vaccinated individuals with heart failure and ischaemic heart disease.
Liang En WEE ; Enoch Xueheng LOY ; Jue Tao LIM ; Yew Woon CHIA ; Shir Lynn LIM ; Jonathan YAP ; Khung Keong YEO ; Derek J HAUSENLOY ; Mark Yan Yee CHAN ; David Chien Boon LYE ; Kelvin Bryan TAN
Annals of the Academy of Medicine, Singapore 2025;54(5):270-282
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*
4.Global incidence and prevalence of nonalcoholic fatty liver disease
Margaret LP TENG ; Cheng Han NG ; Daniel Q. HUANG ; Kai En CHAN ; Darren JH TAN ; Wen Hui LIM ; Ju Dong YANG ; Eunice TAN ; Mark D. MUTHIAH
Clinical and Molecular Hepatology 2023;29(Suppl):S32-S42
Nonalcoholic fatty liver disease (NAFLD) is a leading cause of liver disease worldwide. The estimated global incidence of NAFLD is 47 cases per 1,000 population and is higher among males than females. The estimated global prevalence of NAFLD among adults is 32% and is higher among males (40%) compared to females (26%). The global prevalence of NAFLD has increased over time, from 26% in studies from 2005 or earlier to 38% in studies from 2016 or beyond. The prevalence of NAFLD varies substantially by world region, contributed by differing rates of obesity, and genetic and socioeconomic factors. The prevalence of NAFLD exceeds 40% in the Americas and South-East Asia. The prevalence of NAFLD is projected to increase significantly in multiple world regions by 2030 if current trends are left unchecked. In this review, we discuss trends in the global incidence and prevalence of NAFLD and discuss future projections.
5.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
6.The effect of diabetes and prediabetes on the prevalence, complications and mortality in nonalcoholic fatty liver disease
Cheng Han NG ; Kai En CHAN ; Yip Han CHIN ; Rebecca Wenling ZENG ; Pei Chen TSAI ; Wen Hui LIM ; Darren Jun Hao TAN ; Chin Meng KHOO ; Lay Hoon GOH ; Zheng Jye LING ; Anand KULKARNI ; Lung-Yi Loey MAK ; Daniel Q HUANG ; Mark CHAN ; Nicholas WS CHEW ; Mohammad Shadab SIDDIQUI ; Arun J. SANYAL ; Mark MUTHIAH
Clinical and Molecular Hepatology 2022;28(3):565-574
Background/Aims:
Nonalcoholic fatty liver disease (NAFLD) is closely associated with diabetes. The cumulative impact of both diseases synergistically increases risk of adverse events. However, present population analysis is predominantly conducted with reference to non-NAFLD individuals and has not yet examined the impact of prediabetes. Hence, we sought to conduct a retrospective analysis on the impact of diabetic status in NAFLD patients, referencing non-diabetic NAFLD individuals.
Methods:
Data from the National Health and Nutrition Examination Survey 1999–2018 was used. Hepatic steatosis was defined with United States Fatty Liver Index (US-FLI) and FLI at a cut-off of 30 and 60 respectively, in absence of substantial alcohol use. A multivariate generalized linear model was used for risk ratios of binary outcomes while survival analysis was conducted with Cox regression and Fine Gray model for competing risk.
Results:
Of 32,234 patients, 28.92% were identified to have NAFLD. 36.04%, 38.32% and 25.63% were non-diabetic, prediabetic and diabetic respectively. Diabetic NAFLD significantly increased risk of cardiovascular disease (CVD), stroke, chronic kidney disease, all-cause and CVD mortality compared to non-diabetic NAFLD. However, prediabetic NAFLD only significantly increased the risk of CVD and did not result in a higher risk of mortality.
Conclusions
Given the increased risk of adverse outcomes, this study highlights the importance of regular diabetes screening in NAFLD and adoption of prompt lifestyle modifications to reduce disease progression. Facing high cardiovascular burden, prediabetic and diabetic NAFLD individuals can benefit from early cardiovascular referrals to reduce risk of CVD events and mortality.
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.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
9.Meeting Report: Translational Advances in Cancer Prevention Agent Development Meeting
Mark Steven MILLER ; Peter J. ALLEN ; Powel H. BROWN ; Andrew T. CHAN ; Margie L. CLAPPER ; Roderick H. DASHWOOD ; Shadmehr DEMEHRI ; Mary L. DISIS ; Raymond N. DUBOIS ; Robert J. GLYNN ; Thomas W. KENSLER ; Seema A. KHAN ; Bryon D. JOHNSON ; Karen T. LIBY ; Steven M. LIPKIN ; Susan R. MALLERY ; Emmanuelle J. MEUILLET ; Richard B.S. RODEN ; Robert E. SCHOEN ; Zelton D. SHARP ; Haval SHIRWAN ; Jill M. SIEGFRIED ; Chinthalapally V. RAO ; Ming YOU ; Eduardo VILAR ; Eva SZABO ; Altaf MOHAMMED
Journal of Cancer Prevention 2021;26(1):71-82
The Division of Cancer Prevention of the National Cancer Institute (NCI) and the Office of Disease Prevention of the National Institutes of Health co-sponsored the Translational Advances in Cancer Prevention Agent Development Meeting on August 27 to 28, 2020. The goals of this meeting were to foster the exchange of ideas and stimulate new collaborative interactions among leading cancer prevention researchers from basic and clinical research; highlight new and emerging trends in immunoprevention and chemoprevention as well as new information from clinical trials; and provide information to the extramural research community on the significant resources available from the NCI to promote prevention agent development and rapid translation to clinical trials. The meeting included two plenary talks and five sessions covering the range from pre-clinical studies with chemo/immunopreventive agents to ongoing cancer prevention clinical trials. In addition, two NCI informational sessions describing contract resources for the preclinical agent development and cooperative grants for the Cancer Prevention Clinical Trials Network were also presented.
10.Meeting Report: Translational Advances in Cancer Prevention Agent Development Meeting
Mark Steven MILLER ; Peter J. ALLEN ; Powel H. BROWN ; Andrew T. CHAN ; Margie L. CLAPPER ; Roderick H. DASHWOOD ; Shadmehr DEMEHRI ; Mary L. DISIS ; Raymond N. DUBOIS ; Robert J. GLYNN ; Thomas W. KENSLER ; Seema A. KHAN ; Bryon D. JOHNSON ; Karen T. LIBY ; Steven M. LIPKIN ; Susan R. MALLERY ; Emmanuelle J. MEUILLET ; Richard B.S. RODEN ; Robert E. SCHOEN ; Zelton D. SHARP ; Haval SHIRWAN ; Jill M. SIEGFRIED ; Chinthalapally V. RAO ; Ming YOU ; Eduardo VILAR ; Eva SZABO ; Altaf MOHAMMED
Journal of Cancer Prevention 2021;26(1):71-82
The Division of Cancer Prevention of the National Cancer Institute (NCI) and the Office of Disease Prevention of the National Institutes of Health co-sponsored the Translational Advances in Cancer Prevention Agent Development Meeting on August 27 to 28, 2020. The goals of this meeting were to foster the exchange of ideas and stimulate new collaborative interactions among leading cancer prevention researchers from basic and clinical research; highlight new and emerging trends in immunoprevention and chemoprevention as well as new information from clinical trials; and provide information to the extramural research community on the significant resources available from the NCI to promote prevention agent development and rapid translation to clinical trials. The meeting included two plenary talks and five sessions covering the range from pre-clinical studies with chemo/immunopreventive agents to ongoing cancer prevention clinical trials. In addition, two NCI informational sessions describing contract resources for the preclinical agent development and cooperative grants for the Cancer Prevention Clinical Trials Network were also presented.

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