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Spectrum concept of neuroleptic malignant syndrome

Adityanjee, Singh S, Singh G, Ong S

Br J Psychiatry, 1988 Jul;153:107-11.
PMID: 3224231

Although neuroleptic malignant syndrome (NMS) was initially thought to be a rare, idiosyncratic complication, the incidence estimates have been rising over the years. A part of this increase can be explained on the basis of an over-inclusive definition of NMS. The unitary concept of NMS has been challenged recently and a spectrum concept has been enunciated on the basis of findings of retrospective chart-reviews which have used too broad a definition of NMS. The authors describe three cases of neuroleptic-related toxicity with different clinical presentations which appeared in a manner apparently supporting the spectrum concept. They discuss this controversial concept critically, however, and caution against its overzealous use in routine clinical practice owing to its far-reaching clinical implications.
Fulltext Complete Heart Block as a Clinical Feature in Critically Ill Coronavirus Disease 2019 (COVID-19) Patients: A Case Series of Three Cases

Ahmad F, Gandre P, Nguekam J, Wall A, Ong S, Karuppamakkantakath AN, et al.

Case Rep Crit Care, 2021;2021:9955466.
PMID: 34422417 DOI: 10.1155/2021/9955466

Background. Novel coronavirus-19 disease (COVID-19) is associated with significant cardiovascular morbidity and mortality. However, there have been very few reports on complete heart block (CHB) associated with COVID-19. This case series describes clinical characteristics, potential mechanisms, and short-term outcomes of critically ill COVID-19 patients complicated by CHB. Case Summary. We present three cases of new-onset CHB in critically ill COVID-19 patients. Patient 1 is a 41-year-old male with well-documented history of Familial Mediterranean Fever (FMF) who required mechanical ventilator support for acute hypoxic respiratory failure from severe COVID-19 pneumonia. He developed new-onset CHB without a hemodynamic derangement but subsequently had acute coronary syndrome complicated by cardiogenic shock. Patient 2 is a 77-year-old male with no past medical history who required intubation for severe COVID-19 pneumonia acute hypoxic respiratory failure. He developed CHB with sinus pause requiring temporary pacing but subsequently developed multiorgan failure. Patient 3 is 36-year-old lady 38 + 2 weeks pregnant, gravida 2 para 1 with no other medical history, who had an emergency Lower Section Caesarean Section (LSCS) as she required intubation for acute hypoxic respiratory failure. She exhibited new-onset CHB without hemodynamic compromise. The CHB resolved spontaneously after 24 hours. Discussion. COVID-19-associated CHB is a very rare clinical manifestation. The potential mechanisms for CHB in patients with COVID-19 include myocardial inflammation or direct viral infiltration as well as other causes such as metabolic derangements or use of sedatives. Patients diagnosed with COVID-19 should be monitored closely for the development of bradyarrhythmia and hemodynamic instability.
Fulltext Clinicopathological Features of Telbivudine-Associated Myopathy

Ambang T, Tan JS, Ong S, Wong KT, Goh KJ

PLoS One, 2016;11(9):e0162760.
PMID: 27611456 DOI: 10.1371/journal.pone.0162760

Telbivudine, a thymidine nucleoside analog, is a common therapeutic option for chronic hepatitis B infection. While raised serum creatine kinase is common, myopathy associated with telbivudine is rare. Reports on its myopathological features are few and immunohistochemical analyses of inflammatory cell infiltrates have not been previously described. We describe the clinical, myopathological and immunohistochemical features of four patients who developed myopathy after telbivudine therapy for chronic hepatitis B infection. All four patients presented with progressive proximal muscle weakness, elevation of serum creatine kinase and myopathic changes on electromyography. Muscle biopsies showed myofiber degeneration/necrosis, regeneration, and fibers with cytoplasmic bodies and cytochrome c oxidase deficiency. There was minimal inflammation associated with strong sarcolemmal overexpression of class I major histocompatibility complex (MHC class I). Upon withdrawal of telbivudine, muscle weakness improved in all patients and eventually completely resolved in three. In our series, telbivudine-associated myopathy is characterized by necrotizing myopathy which improved on drug withdrawal. Although the occasional loss of cytochrome c oxidase is consistent with mitochondrial toxicity, the overexpression of MHC class I in all patients could suggest an underlying immune-mediated mechanism which may warrant further investigation.
Clinical applications of renal arteriography

Ang AH, Lambeth JT, Soo YS, Ong SC

Med J Malaya, 1970 Sep;25(1):8-16.
PMID: 4249503
Familial neuromyelitis optica spectrum disorder in a pair of sisters

Cheo SW, Ong SAM, Low QJ, Tan YA, Chia YK

QJM, 2020 Oct 01;113(10):743-746.
PMID: 32240316 DOI: 10.1093/qjmed/hcaa107
Effectiveness of nirmatrelvir/ritonavir (Paxlovid®) in preventing hospitalisation and death among COVID-19 patients: a prospective cohort study

Chew LS, Lim XJ, Chang CT, Kamaludin RS, Leow HL, Ong SY, et al.

Med J Malaysia, 2023 Sep;78(5):602-608.
PMID: 37775486

INTRODUCTION: Previous trials and real-world studies have shown that nirmatrelvir/ritonavir (Paxlovid®) reduces hospitalisation and deaths in symptomatic, high-risk, nonsevere COVID-19 patients. However, there was a scarcity of data on its effectiveness in the local setting. This study aimed to determine the effectiveness of Paxlovid® in reducing hospitalisation and mortality among COVID-19 patients and to identify the types of adverse events that occur after taking Paxlovid®.
MATERIALS AND METHODS: A two-arm prospective cohort study was conducted among adult patients with COVID-19 categories 2 and 3 treated with Paxlovid® and a matched control group. A standard risk-stratified scoring system was used to establish Paxlovid® eligibility. All patients who were prescribed Paxlovid® and took at least one dose of Paxlovid® were included in the study. The control patients were selected from a centralised COVID-19 patient registry and matched based on age, gender and COVID-19 stage severity.
RESULTS: A total of 552 subjects were included in the study and evenly allocated to the treatment and control groups. There was no statistically significant difference in 28-day hospitalisation after diagnosis [Paxlovid®: 26 (9.4%), Control: 34 (12.3%), OR: 0.74; 95%CI, 0.43-1.27; p=0.274] or all-cause death [Paxlovid®: 2 (0.7%), Control: 3 (1.1%), OR 1.51; 95%CI, 0.25-9.09; p=0.999]. There was no significant reduction in hospitalisation duration, intensive care unit admission events or supplementary oxygen requirement in the treatment arm. Ethnicity, COVID-19 severity at diagnosis, comorbidities and vaccination status were predictors of hospitalisation events.
CONCLUSION: In this two-arm study, Paxlovid® did not significantly lower the incidence of hospitalisation, all-cause death and the need for supplemental oxygen. Adverse effects were frequent but not severe. Paxlovid® efficacy varied across settings and populations, warranting further real-world investigations.
Yeasts in sputum

Chin CS, Ong SC

Med J Malaysia, 1979 Jun;33(4):326-30.
PMID: 522744
Science stars of East Asia

Cyranoski D, Law YH, Ong S, Phillips N, Zastrow M

Nature, 2018 06;558(7711):502-510.
PMID: 29950631 DOI: 10.1038/d41586-018-05506-1
Fulltext DJ-1 protects against cell death following acute cardiac ischemia-reperfusion injury

Dongworth RK, Mukherjee UA, Hall AR, Astin R, Ong SB, Yao Z, et al.

Cell Death Dis, 2014 Feb 27;5:e1082.
PMID: 24577080 DOI: 10.1038/cddis.2014.41

Novel therapeutic targets are required to protect the heart against cell death from acute ischemia-reperfusion injury (IRI). Mutations in the DJ-1 (PARK7) gene in dopaminergic neurons induce mitochondrial dysfunction and a genetic form of Parkinson's disease. Genetic ablation of DJ-1 renders the brain more susceptible to cell death following ischemia-reperfusion in a model of stroke. Although DJ-1 is present in the heart, its role there is currently unclear. We sought to investigate whether mitochondrial DJ-1 may protect the heart against cell death from acute IRI by preventing mitochondrial dysfunction. Overexpression of DJ-1 in HL-1 cardiac cells conferred the following beneficial effects: reduced cell death following simulated IRI (30.4±4.7% with DJ-1 versus 52.9±4.7% in control; n=5, P<0.05); delayed mitochondrial permeability transition pore (MPTP) opening (a critical mediator of cell death) (260±33 s with DJ-1 versus 121±12 s in control; n=6, P<0.05); and induction of mitochondrial elongation (81.3±2.5% with DJ-1 versus 62.0±2.8% in control; n=6 cells, P<0.05). These beneficial effects of DJ-1 were absent in cells expressing the non-functional DJ-1(L166P) and DJ-1(Cys106A) mutants. Adult mice devoid of DJ-1 (KO) were found to be more susceptible to cell death from in vivo IRI with larger myocardial infarct sizes (50.9±3.5% DJ-1 KO versus 41.1±2.5% in DJ-1 WT; n≥7, P<0.05) and resistant to cardioprotection by ischemic preconditioning. DJ-1 KO hearts showed increased mitochondrial fragmentation on electron microscopy, although there were no differences in calcium-induced MPTP opening, mitochondrial respiratory function or myocardial ATP levels. We demonstrate that loss of DJ-1 protects the heart from acute IRI cell death by preventing mitochondrial dysfunction. We propose that DJ-1 may represent a novel therapeutic target for cardioprotection.
Type 2 diabetes in youth from the Western Pacific region: glycaemic control, diabetes care and complications

Eppens MC, Craig ME, Jones TW, Silink M, Ong S, Ping YJ, et al.

Curr Med Res Opin, 2006 May;22(5):1013-20.
PMID: 16709323 DOI: 10.1185/030079906X104795

OBJECTIVE: To describe the glycaemic control, diabetes care and prevalence of complications in youth with type 2 diabetes from the Western Pacific Region.
RESEARCH DESIGN AND METHODS: Cross-sectional, clinic-based audit of 331 patients aged < 18 years from 56 centres in Australia, China-Beijing, China-Shanghai, China-Hong Kong, Indonesia, Japan, South Korea, Malaysia, Philippines, Singapore, Taiwan and Thailand. Clinical and management data were recorded along with glycated haemoglobin (HbA(1c)), lipids and complication rates.
MAIN OUTCOME MEASURES: Glycaemic control, complications, diabetes management.
RESULTS: Median age was 14.9 years (interquartile range 13.2-16.4 years) and median diabetes duration 2.3 years (1.4-3.6 years). Median HbA(1c) was 7% (5.9-9.9%) and HbA(1c) was > 7.5% in 40% of patients. In multiple regression analysis, glycaemic control varied significantly between countries (p = 0.02); higher HbA(1c) was associated with fewer home blood glucose measurements (p = 0.005) and higher insulin dose/kg (p < 0.0001). Blood glucose monitoring was performed by 65% of patients (range 33-96% by country). In 25% of patients, management consisted of diet alone or no treatment (range 0-53% by country); oral anti-diabetic drugs alone were used in 49%, insulin alone in 11% and both in 15%. Microalbuminuria was found in 8% and hypertension in 24%. The risk of hypertension increased with higher BMI (OR 1.16, 95% CI 1.09-1.24, p < 0.0001); antihypertensive agents were used in 4% of patients.
CONCLUSIONS: The management of type 2 diabetes in youth from the Western Pacific Region varies widely. Hypertension and microalbuminuria were frequent, but not commonly treated. Further investigation into the natural history and risk factors for complications in youth with type 2 diabetes is required to assist in developing evidence based management guidelines.
Fulltext Fructans in the first 1000 days of life and beyond, and for pregnancy

Firmansyah A, Chongviriyaphan N, Dillon DH, Khan NC, Morita T, Tontisirin K, et al.

Asia Pac J Clin Nutr, 2016 Dec;25(4):652-675.
PMID: 27702710 DOI: 10.6133/apjcn.092016.02

Inulin-based prebiotics are non-digestible polysaccharides that influence the composition of the gut microbiota in infants and children, notably eliciting a bifidogenic effect with high short chain fatty acid levels. Inulin, a generic term that comprises β-(2,1)-linked linear fructans, is typically isolated from the chicory plant root, and derivatives such as oligofructose and long chain inulin appear to have different physiological properties. The first 1000 days of a child's life are increasingly recognized as a critical timeframe for health also into adulthood, whereby nutrition plays a key role. There is an ever increasing association between nutrition and gut microbiota composition and development, with life health status of an individual. This review summarizes the latest knowledge in the infant gut microbiota from preterms to healthy newborns, as well as in malnourished children in developing countries. The impact of inulin or mixtures thereof on infants, toddlers and young children with respect to intestinal function and immunity in general, is reviewed. Possible benefits of prebiotics to support the gut microbiome of malnourished infants and children, especially those with infections in the developing world, are considered, as well as for the pregnant mothers health. Importantly, novel insights in metabolic programming are covered, which are being increasing recognized for remarkable impact on long term offspring health, and eventual potential beneficial role of prebiotic inulins. Overall increasing findings prompt the potential for gut microbiota-based therapy to support health or prevent the development of certain diseases from conception to adulthood where inulin prebiotics may play a role.
Antithrombotic effects of hydroxychloroquine in a pregnant patient with Antiphospholipid syndrome and recurrent venous thromboembolism

Gan SP, Ong SG

Med J Malaysia, 2017 04;72(2):124-125.
PMID: 28473677 MyJurnal

A pregnant woman with antiphospholipid syndrome presented with repeated venous thromboembolism (VTE) in the first and second trimesters of pregnancy despite receiving combination therapy with low-molecular-weight heparin and aspirin. The addition of hydroxychloroquine prevented further VTE recurrence, thus demonstrating its potential antithrombotic effects.
Fulltext Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life Years for 29 Cancer Groups From 2010 to 2019: A Systematic Analysis for the Global Burden of Disease Study 2019

Global Burden of Disease 2019 Cancer Collaboration, Kocarnik JM, Compton K, Dean FE, Fu W, Gaw BL, et al.

JAMA Oncol, 2022 Mar 01;8(3):420-444.
PMID: 34967848 DOI: 10.1001/jamaoncol.2021.6987

IMPORTANCE: The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden.
OBJECTIVE: To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019.
EVIDENCE REVIEW: The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs).
FINDINGS: In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles.
CONCLUSIONS AND RELEVANCE: The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world.
Recurrent spontaneous subdural hematoma secondary to immune thrombocytopenia in a patient with overlap syndrome

Goh KG, Ong SG

Lupus, 2015 Jan;24(1):90-3.
PMID: 25305213 DOI: 10.1177/0961203314554248

Patients with autoimmune connective tissue disease may manifest as overlap syndrome with features of systemic lupus erythematosus (SLE), systemic sclerosis, rheumatoid arthritis and myositis. Those presenting with active SLE can present with immune thrombocytopenia (IT) and may be complicated with subdural hematoma which, though rare, is potentially life-threatening. We report here a patient with overlap syndrome who had recurrent spontaneous subdural hematoma due to severe thrombocytopenia which did not respond to corticosteroids and azathioprine. Her platelet count became normal with three doses of low-dose intravenous cyclophosphamide (IV CYC) given at 3-weekly intervals. She remained in remission with maintenance therapy with azathioprine.
Eating disorders in Hong Kong

Goh SE, Ong SB, Subramaniam M

Br J Psychiatry, 1993 Feb;162:276-7.
PMID: 8435714
Fulltext Massive pericardial effusion in primary hypothyroidism

Hanip MR, Ong SB, Tan TT, Khalid BA

Med J Malaysia, 1989 Dec;44(4):341-3.
PMID: 2520045

A 44 year old lady with primary hypothyroidism presented with massive pericardial effusion without cardiac tamponade. Pericardial tap was done twice and the effusion resolved as the hypothyroid state improved. She remained hypertensive despite the euthyroid state. She was discharged well with L-thyroxine and anti-hypertensive therapy.
Mindfulness-based therapy for smoking cessation and mental health: a randomised controlled trial

Hemanath S, Robinson F, Pang NTP, Lim EK, Ong SJ, Alyssa S, et al.

Med J Malaysia, 2023 May;78(3):336-343.
PMID: 37271843

INTRODUCTION: Effective smoking cessation programmes are essential for assisting smokers in quitting, indirectly lowering mortality and morbidity associated with smoking. Numerous studies have indicated positive outcomes when using mindfulness treatment (MT) to treat psychological or behavioural health issues. Although to date, no study has looked at the effectiveness of online MT for quitting smoking while addressing mental health, particularly among the Asian population. Therefore, this study compares the efficiency of online MT to traditional counselling therapy (CT) in aiding smoking cessation programmes while also addressing mental health.
MATERIALS AND METHODS: A randomised control study with a two-group, single-blind design and baseline evaluation was selected. Social media sites were used to advertise for participants, who were then admitted after meeting the requirements. Participants who met the eligibility requirements were randomly split into two groups. Each group received a total of three sessions of online therapy (MT or CT), once every two weeks, as well as one phone call per week as reinforcement. At the beginning and end of the intervention, participants completed questionnaires (1st week and 5th week). Generalized Estimating Equation (GEE) statistical analysis was used to analyse all the variables.
RESULTS: The MT group experienced a statistically significant decrease in cigarette consumption (β: -3.50, 95% Wald CI: - 4.62, -2.39) compared to the CT group over time. Furthermore, the MT group demonstrated significant improvements in their scores for the AAQ-2, anxiety, stress, depression and mindfulness compared to the CT group.
CONCLUSION: Online MT is more successful at assisting smokers in lowering their daily cigarette intake and supporting their mental health during the smoking cessation process. Further longitudinal comparisons of the effectiveness of online MT should be undertaken using online platforms in future studies.
Fulltext TiO2-LiF composite coating for improving NCM622 cathode cycling stability: one-step construction

Huang K, Zhou J, Yang H, Xie T, Lan T, Ong S, et al.

RSC Adv, 2023 Nov 16;13(48):33905-33910.
PMID: 38019995 DOI: 10.1039/d3ra05659g

The Ni-rich NCM622 is a promising cathode material for future high energy lithium ion batteries, but unstable electrochemical performance of NCM622 hinder its large scale commercial application. The cycling peformance of nickel-rich LiNi0.6Co0.2Mn0.2O2 (NCM622) cathode materials can be improved by surface coating. Here, a one-step approach based on TiF4 is used to successfully manufacture modified NCM622 cathode materials with a TiO2-LiF coating. The TiO2-LiF coated NCM622 preserves 79.7% capacity retention which is higher than the pure NCM622 (68.9%) at 1C after 200 cycles within 2.7-4.3 V. This material serves as the cathode for lithium-ion batteries (LIBs). The uniform TiO2-LiF coating layer can alleviate structural degradation brought on by unfavorable side reactions with the electrolyte has been validated. TiO2-LiF coated on NCM622 cathode materials can be modified easily by one-step approach.
Termination of pregnancy in cases of intrauterine fetal death, missed abortion, molar and anencephalic pregnancy with intramuscular administration of 2a 2b dihomo 15(S) 15 methyl PGF2 alpha methyl ester--a multicentre study

Karim SM, Ratnam SS, Hutabarat H, Hanafiah J, Simanjuntak P, Teoh SK, et al.

Ann Acad Med Singap, 1982 Oct;11(4):508-12.
PMID: 7165272

2a 2b dihomo 15(S) 15 methyl PGF2 alpha methyl ester (dihomo 15 me PGF2 alpha) in intramuscular doses of 0.5 mg 8 hourly was used in 631 patients with abnormal intrauterine pregnancy comprising 282 cases of intrauterine fetal death, 233 cases of missed abortion, 34 and 82 cases respectively anencephalic and molar pregnancies. The study was carried out as a collaborative project between the University Departments of Obstetrics and Gynaecology in Singapore (Singapore), Medan (Indonesia) and Kuala Lumpur (Malaysia) during the period June 1974 and November 1979. Six hundred patients (95.1%) aborted or delivered in a mean time of 11.3 hours (S.D. +/- 7.0) with an average of 1.8 injections of the prostaglandin analogue per patient. Side effects included vomiting (23.6%; mean 0.45 episodes per patient), diarrhoea (44.4%; mean 1.00 episode per patient), cold and shivering (11.9%) and pyrexia (12.4%). One patient sustained a cervical laceration which did not require repair. There were no complications.
Paradoxical worsening of chest radiographs secondary to immune reconstitution syndrome (IRIS) in a patient with advanced HIV infection and Rhodococcus pneumonia

Koh KC, Ibrahim NM, Ong SCL

Med J Malaysia, 2020 03;75(2):164-166.
PMID: 32281599

We present a rare case of post-antiretroviral therapy (ART) paradoxically worsening of radiological findings in a patient with advanced HIV-infection on treatment for Rhodococcus pneumonia who was misdiagnosed with pulmonary tuberculosis. Despite clinical improvement, serial chest radiographs showed deteriorations a month after starting ART. This was attributed to Immune Reconstitution Inflammatory Syndrome (IRIS) which spontaneously resolved without any treatment.

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