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A doctor's duty is to heal the unhealthy: the story of Tun Dr Mahathir Mohamad

Ong HT

Ann Acad Med Singap, 2005 Jul;34(6):45C-51C.
PMID: 16010379

Mahathir Mohamad was born in 1925 in Alor Star, Kedah. He entered the King Edward VII College of Medicine in Singapore in 1947 and graduated in 1953. His years in the medical school equipped young Mahathir with the training necessary to assess and diagnose a problem, before dispensing the appropriate treatment. Throughout his later years in the political limelight, Dr Mahathir recognised the very important role the medical college had in laying the strong foundation for his successful career. He joined UMNO in 1945, already interested in politics at the tender age of 20; he was first elected into Parliament in 1964. The vigorous expression of his candid views did not go down well during the troubled days following the 13 May 1969 racial riots and he was expelled from UMNO, his writings were banned, and he was considered a racial extremist. Nevertheless, his intellectual and political influence could not be ignored for long; he returned to Parliament in 1974, and became the fourth, and longest serving, Prime Minister of Malaysia in 1981. Dr Mahathir has found fame as a Malay statesman, and an important Asian leader of the twentieth century with much written, locally and internationally, debating his policies. This article, using Dr Mahathir's own writings, starts with his description of his early life, proceeds to look at his medical career, then touches on his diagnosis of the problems plaguing the Malays, before concluding with his views on the need to stand up to the prejudices and pressures of the Western world. Throughout his life, Dr Mahathir behaved as the ever-diligent medical doctor, constantly studying the symptoms to diagnose the cause of the ills in his community and country, before proceeding to prescribe the correct treatment to restore good health. It is a measure of his integrity and intellectual capability that he did not seek to hide his failures, or cite unfinished work in an attempt to cling to political power.
Fulltext Impact of various continuing medical education activities on clinical practice - a survey of Malaysian doctors on its perceived importance

Loh LC, Ong HT, Quah SH

Ann Acad Med Singap, 2007 Apr;36(4):281-4.
PMID: 17483859

INTRODUCTION: Medical talks, newsletter circulars, scientific meetings and conferences, and interaction with members of the pharmaceutical industry, have become convenient means of carrying out continuing medical education (CME) for many busy doctors.

MATERIALS AND METHODS: To study the perceived importance of these various CME activities, a self-completed posted questionnaire survey was conducted among registered practitioners of a densely populated urban state in Malaysia.

RESULTS: Of the 172 respondents [male, 77%; hospital-based, 37%; general practitioner (GP), 55%; private practice, 70%; respondent rate of 19.5%], most preferred local conferences and endorsements by local experts to their foreign counterparts. Meetings or conferences sponsored by the pharmaceutical industry were ranked similarly with those without such links, while the reputation of the pharmaceutical firms was of foremost importance. Among GPs (n = 95) and non-GPs (n = 77), medical society newsletters were rated significantly higher by GPs while overseas conferences were rated higher by non-GPs.

CONCLUSION: Our findings provide an important first look at this under-explored area among Malaysian doctors and described a high degree of acceptance for the involvement of the pharmaceutical industry in CME activities.
Circular RNA ZNF800 (hsa_circ_0082096) regulates cancer stem cell properties and tumor growth in colorectal cancer

Rengganaten V, Huang CJ, Wang ML, Chien Y, Tsai PH, Lan YT, et al.

BMC Cancer, 2023 Nov 10;23(1):1088.
PMID: 37950151 DOI: 10.1186/s12885-023-11571-1

BACKGROUND: Cancer stem cells form a rare cell population in tumors that contributes to metastasis, recurrence and chemoresistance in cancer patients. Circular RNAs (circRNAs) are post-transcriptional regulators of gene expression that sponge targeted microRNA (miRNAs) to affect a multitude of downstream cellular processes. We previously showed in an expression profiling study that circZNF800 (hsa_circ_0082096) was up-regulated in cancer stem cell-enriched spheroids derived from colorectal cancer (CRC) cell lines.
METHODS: Spheroids were generated in suspension spheroidal culture. The ZNF800 mRNA, pluripotency stem cell markers and circZNF800 levels were determined by quantitative RT-PCR. CircZNF800-miRNA interactions were shown in RNA pulldown assays and the miRNA levels determined by stem-loop qRT-PCR. The effects of circZNF800 on cell proliferation were tested by EdU staining followed by flowcytometry. Expression of stem cell markers CD44/CD133, Lgr5 and SOX9 was demonstrated in immunofluorescence microscopy. To manipulate the cellular levels of circZNF800, circZNF800 over-expression was achieved via transfection of in vitro synthesized and circularized circZNF800, and knockdown attained using a CRISPR-Cas13d-circZNF800 vector system. Xenografted nude mice were used to demonstrate effects of circZNF800 over-expression and knockdown on tumor growth in vivo.
RESULTS: CircZNF800 was shown to be over-expressed in late-stage tumor tissues of CRC patients. Data showed that circZNF800 impeded expression of miR-140-3p, miR-382-5p and miR-579-3p while promoted the mRNA levels of ALK/ACVR1C, FZD3 and WNT5A targeted by the miRNAs, as supported by alignments of seed sequences between the circZNF800-miRNA, and miRNA-mRNA paired interactions. Analysis in CRC cells and biopsied tissues showed that circZNF800 positively regulated the expression of intestinal stem cell, pluripotency and cancer stem cell markers, and promoted CRC cell proliferation, spheroid and colony formation in vitro, all of which are cancer stem cell properties. In xenografted mice, circZNF800 over-expression promoted tumor growth, while circZNF800 knockdown via administration of CRISPR Cas13d-circZNF800 viral particles at the CRC tumor sites impeded tumor growth.
CONCLUSIONS: CircZNF800 is an oncogenic factor that regulate cancer stem cell properties to lead colorectal tumorigenesis, and may be used as a predictive marker for tumor progression and the CRISPR Cas13d-circZNF800 knockdown strategy for therapeutic intervention of colorectal cancer.
Fulltext Beta blockers in hypertension and cardiovascular disease

Ong HT

BMJ, 2007 May 5;334(7600):946-9.
PMID: 17478848
Epidemiology of West syndrome in Singapore

Lee WL, Ong HT

Brain Dev, 2001 Nov;23(7):584-5.
PMID: 11701260

The incidence of West syndrome (WS) was determined by a search of reports of electroencephalograms (EEG) recorded in 1998 and 1999 in all public hospitals in Singapore. Amongst records of patients born in 1998, nine were found with EEG features of hypsarrhythmia or modified hypsarrhythmia with onset of seizures between January 1,1998 and December 31, 1999. The medical records of these patients were reviewed. The population of children born in 1998 was 43,664. In 1998 and 1999, 67% of all hospital admissions for patients 2 years or younger in Singapore were in public hospitals. The cumulative incidence of WS in Singapore corrected for the percentage of hospital admissions to public hospitals was 3.1/10,000 live births. The corrected cumulative incidences in Chinese, Malays and Indians were 2.7, 3.1 and 3.3 per 10,000, respectively. Three cases were idiopathic; three were due to congenital structural lesions of the brain; one each had periventricular leucomalacia, intracranial hemorrhage and severe intrauterine growth retardation. None of the patients were normal at follow up. The three patients with idiopathic WS had mild global developmental delay and the other six cases had cerebral palsy and severe mental retardation. With the best modern medical treatment, possibly only two of the nine cases of WS may have been prevented.
Statin alternatives or just placebo: an objective review of omega-3, red yeast rice and garlic in cardiovascular therapeutics

Ong HT, Cheah JS

Chin Med J (Engl), 2008 Aug 20;121(16):1588-94.
PMID: 18982874

The aim of this review is to objectively access the trial evidence on the role of omega-3, red yeast rice and garlic in preventing clinical cardiovascular events. Given the large number of clinical trials favoring statin use in cardiovascular disease, it is important to see if evidence is available for these supplements and whether they could replace statin therapy.
Migration of endocrine-disrupting chemicals into food from plastic packaging materials: an overview of chemical risk assessment, techniques to monitor migration, and international regulations

Ong HT, Samsudin H, Soto-Valdez H

Crit Rev Food Sci Nutr, 2022;62(4):957-979.
PMID: 33081493 DOI: 10.1080/10408398.2020.1830747

Plastic packaging materials (PPMs) protect food from contamination, maintain quality, and ease transportation and distribution. Additives included during the manufacturing and processing of PPMs improve flexibility, durability, barrier properties, and sometimes aid the processing itself. During processing, these additives, even the monomers used to produce the plastics, can produce side products or breakdown products as a result of degradation and various chemical reactions. These starting substances and reaction products include 2,2-bis(4-hydroxyphenyl)propane (bisphenol A), phthalates/phthalic acid esters, alkylphenols, and bis(2-ethylhexyl) adipate, which are considered endocrine-disrupting chemicals (EDCs) that may interfere with the human endocrine system and produce adverse reproductive, neurological, developmental, and immune effects. When in contact with food, EDCs can migrate into food if conditions are appropriate, thereby possibly jeopardizing food safety. Chemical risk assessment and regulatory control were developed to reduce human exposure to harmful migrated EDCs. This article gives an overview of the migration of EDCs from PPMs and control measures to reduce the risk of adverse impacts on human health.
Fulltext Anxiety and coping strategies during the COVID-19 pandemic: A cross-sectional study of staff and students from a tertiary education center in Malaysia

Lee KW, Yap SF, Ong HT, Pheh KS, Lye MS

Front Public Health, 2022;10:936486.
PMID: 36276401 DOI: 10.3389/fpubh.2022.936486

AIM: We examined the anxiety levels and coping strategies among staff and students of a tertiary educational institution during the COVID-19 pandemic and determined the association between anxiety level and coping strategies.
METHOD: Through an online survey, we used Coronavirus Anxiety Scale (CAS) to measure the level of anxiety associated with the COVID-19 crisis and Brief Coping Orientation to Problems Experienced (COPE) to assess the coping responses adopted to handle stressful life events. Coping strategies were classified as adaptive and maladaptive, for which the aggregate sores were calculated. Multiple linear regression was used to determine the predictors of anxiety adjusted for potentially confounding variables. Results from 434 participants were available for analysis.
RESULTS: The mean score (SD) of the CAS was 1.1 (1.8). The mean scores of adaptive and maladaptive coping strategies were 35.69 and 19.28, respectively. Multiple linear regression revealed that maladaptive coping [Adjusted B coefficient = 4.106, p-value < 0.001] and presence of comorbidities [Adjusted B coefficient = 1.376, p-value = 0.025] significantly predicted anxiety.
CONCLUSION: Maladaptive coping and presence of comorbidities were the predictors of coronavirus anxiety. The apparent lack of anxiety in relation to COVID-19 and movement restriction is reflective of the reported high level of satisfaction with the support and services provided during the COVID-19 outbreak in Malaysia. Adaptive coping strategies were adopted more frequently than maladaptive. Nevertheless, public education on positive coping strategies and anxiety management may be still be relevant to provide mental health support to address the needs of the general population.
Fulltext Knowledge, Perceptions and Behaviors Related to COVID-19 in a University Setting in Malaysia

Lee KW, Yap SF, Ong HT, Leong PP, Mohamad Hatta N, Lye MS

Front Public Health, 2022;10:873022.
PMID: 35480574 DOI: 10.3389/fpubh.2022.873022

BACKGROUND: In Malaysia the COVID-19 disease (COVID-19) has continued to escalate since its first detection in late January 2020, despite widespread implementation of control measures. This study aims to determine the knowledge, perception and behaviors with respect to COVID-19 in the midst of the third wave of the infection.
METHODS: A cross-sectional study was carried out among staffs and students of Universiti Tunku Abdul Rahman (UTAR). The survey consists of basic sociodemographic information, 22 items on knowledge on COVID-19, 3 items on perceived self-risk, 2 items on preparedness & perceived self-efficacy, 10 items on preventive (own) measures, 9 items assessing unwanted and desirable behaviors during the pandemic. Simple and multiple linear regression were performed to determine the factors associated with knowledge, preventive measures adopted, self-risk perception, preparedness & perceived self-efficacy, and behaviors.
RESULTS: A total of 434 responded to the survey of whom the majority (85.1%) had high scores for knowledge (mean score of 18.72 out of 22). A significant positive association was found between knowledge and older age (adjusted B coefficient (SE) = 0.046 (0.022), p = 0.039), those from medical faculty (adjusted B coefficient (SE) = 0.870 (0.420), p = 0.039) and residence in high-risk areas (adjusted B coefficient (SE) = 0.831 (0.295), p = 0.005). Predictors for higher perception of COVID-19 risk included presence of COVID-19 cases among social contacts (adjusted B coefficient (SE) = 0.751 (0.308), p = 0.015) and living with elderly (adjusted B coefficient (SE) = 1.137 (0.296), p < 0.001), while that for perception of preparedness and self-efficacy were living with children (adjusted Beta coefficient (SE) = 0.440 (0.173), p = 0.011) and absence of positive cases among social contacts (adjusted B coefficient (SE) = 0.418 (0.183), p = 0.023). Good preventive measures among the respondents were positively associated with knowledge (adjusted B coefficient (SE) = 0.116 (0.025), p < 0.001), as well as with female gender (adjusted B coefficient (SE) = 0.348 (0.142), p = 0.014). Unwanted behavior was significantly associated with male gender (adjusted B coefficient (SE) = 0.664 (0.321), p = 0.039) and COVID-19 positive status (adjusted B coefficient (SE) = 9.736 (3.297), p = 0.003). Knowledge of COVID-19 (adjusted B coefficient (SE) = 0.069 (0.035), p = 0.048) and being married (adjusted B coefficient (SE) = 0.917 (0.462), p = 0.048) were the predictors of desirable behavior.
CONCLUSION: Overall, the UTAR community had demonstrated a good level of knowledge and preventive behaviors, albeit with some areas for improvement.
Mental stress, atheroma, myocardial ischaemia and injury: the link is inflammation

Ong HT, Chen J

Gen Psychiatr, 2023;36(6):e101282.
PMID: 38155845 DOI: 10.1136/gpsych-2023-101282

Increasing observational and experimental trial data have shown that mental stress can lead to an increase in adverse clinical cardiovascular events. Mental stress affects the heart by inducing ischaemia and precipitating myocardial infarction (MI) or direct myocardial injury. Mental stress leads to systemic inflammation. Inflammation is known to cause rapid atheromatous plaque progression, instability and thrombosis-the classic type 1 MI. Inflammation can also lead to type 2 MI or myocarditis and injury. The published data linking systemic inflammation, mental stress and cardiovascular disease will be reviewed to establish the linkage between mind and heart, thereby highlighting the importance of holistically managing the patient, not only addressing separate organ systems. Finally, recent trial evidence showing the value of anti-inflammatory drugs in cardiovascular and mental conditions will be briefly considered.
Fulltext Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) in patients at high risk of cardiovascular events: a meta-analysis of 10 randomised placebo-controlled trials

Ong HT, Ong LM, Ho JJ

ISRN Cardiol, 2013;2013:478597.
PMID: 24307952 DOI: 10.1155/2013/478597

Context. Whether angiotensin converting-enzyme inhibitors (ACEI) and angiotensin-receptor blockers (ARB) are useful in high risk patients without heart failure is unclear. We perform a meta-analysis of prospective randomized placebo-controlled ACEI or ARB trials studying patients with a combination of risk factors to assess treatment impact on all cause mortality, cardiovascular mortality, nonfatal myocardial infarction (MI) and stroke. Method. A PubMed search was made for placebo-controlled trials recruiting at least 1,200 high risk patients randomized to either ACEI or ARB, with follow-up of at least 2 years. Meta-analysis was performed using the RevMan 5 program and Mantel-Haenszel analysis was done with a fixed effects model. Results. Ten trials recruiting 77,633 patients were reviewed. All cause mortality was significantly reduced by ACEI (RR 0.89; P = 0.0008), but not by ARB treatment (RR 1.00; P = 0.89). Cardiovascular mortality and nonfatal MI were also reduced in the ACEI trials but not with ARB therapy. Stroke was significantly reduced in the ACEI trials (RR 0.75; P < 0.00001) and more modestly reduced in the ARB trials (RR 0.90; P = 0.01). Conclusion. ACEI treatment reduced stroke, nonfatal MI, cardiovascular and total mortality in high risk patients, while ARB modestly reduced stroke with no effect on nonfatal MI, cardiovascular and total mortality.
Fulltext MicroRNA-362 negatively and positively regulates SMAD4 expression in TGF-β/SMAD signaling to suppress cell migration and invasion

Cheng HP, Huang CJ, Tsai ML, Ong HT, Cheong SK, Choo KB, et al.

Int J Med Sci, 2021;18(8):1798-1809.
PMID: 33746597 DOI: 10.7150/ijms.50871

Cell migration and invasion are modulated by epithelial-to-mesenchymal transition (EMT) and the reverse MET process. Despite the detection of microRNA-362 (miR-362, both the miR-362-5p and -3p species) in cancers, none of the identified miR-362 targets is a mesenchymal or epithelial factor to link miR-362 with EMT/MET and metastasis. Focusing on the TGF-β/SMAD signaling pathway in this work, luciferase assays and western blot data showed that miR-362 targeted and negatively regulated expression of SMAD4 and E-cadherin, but not SNAI1, which is regulated by SMAD4. However, miR-362 knockdown also down-regulated SMAD4 and SNAI1, but up-regulated E-cadherin expression. Wound-healing and transwell assays further showed that miR-362 knockdown suppressed cell migration and invasion, effects which were reversed by over-expressing SMAD4 or SNAI1, or by knocking down E-cadherin in the miR-362 knockdown cells. In orthotopic mice, miR-362 knockdown inhibited metastasis, and displayed the same SMAD4 and E-cadherin expression profiles in the tumors as in the in vitro studies. A scheme is proposed to integrate miR-362 negative regulation via SMAD4, and to explain miR-362 positive regulation of SMAD4 via miR-362 targeting of known SMAD4 suppressors, BRK and DACH1, which would have resulted in SMAD4 depletion and annulment of subsequent involvement in TGF-β signaling actions. Hence, miR-362 both negatively and positively regulates SMAD4 expression in TGF-β/SMAD signaling pathway to suppress cell motility and invasiveness and metastasis, and may explain the reported clinical association of anti-miR-362 with suppressed metastasis in various cancers. MiR-362 knockdown in miR-362-positive cancer cells may be used as a therapeutic strategy to suppress metastasis.
Fulltext Mapping a Circular RNA-microRNA-mRNA-Signaling Regulatory Axis That Modulates Stemness Properties of Cancer Stem Cell Populations in Colorectal Cancer Spheroid Cells

Rengganaten V, Huang CJ, Tsai PH, Wang ML, Yang YP, Lan YT, et al.

Int J Mol Sci, 2020 Oct 23;21(21).
PMID: 33114016 DOI: 10.3390/ijms21217864

Spheroidal cancer cell cultures have been used to enrich cancer stem cells (CSC), which are thought to contribute to important clinical features of tumors. This study aimed to map the regulatory networks driven by circular RNAs (circRNAs) in CSC-enriched colorectal cancer (CRC) spheroid cells. The spheroid cells established from two CRC cell lines acquired stemness properties in pluripotency gene expression and multi-lineage differentiation capacity. Genome-wide sequencing identified 1503 and 636 circRNAs specific to the CRC parental and spheroid cells, respectively. In the CRC spheroids, algorithmic analyses unveiled a core network of mRNAs involved in modulating stemness-associated signaling pathways, driven by a circRNA-microRNA (miRNA)-mRNA axis. The two major circRNAs, hsa_circ_0066631 and hsa_circ_0082096, in this network were significantly up-regulated in expression levels in the spheroid cells. The two circRNAs were predicted to target and were experimentally shown to down-regulate miR-140-3p, miR-224, miR-382, miR-548c-3p and miR-579, confirming circRNA sponging of the targeted miRNAs. Furthermore, the affected miRNAs were demonstrated to inhibit degradation of six mRNA targets, viz. ACVR1C/ALK7, FZD3, IL6ST/GP130, SKIL/SNON, SMAD2 and WNT5, in the CRC spheroid cells. These mRNAs encode proteins that are reported to variously regulate the GP130/Stat, Activin/Nodal, TGF-β/SMAD or Wnt/β-catenin signaling pathways in controlling various aspects of CSC stemness. Using the CRC spheroid cell model, the novel circRNA-miRNA-mRNA axis mapped in this work forms the foundation for the elucidation of the molecular mechanisms of the complex cellular and biochemical processes that determine CSC stemness properties of cancer cells, and possibly for designing therapeutic strategies for CRC treatment by targeting CSC.
Fulltext Are angiotensin-converting enzyme inhibitors and angiotensin receptor blockers especially useful for cardiovascular protection?

Ong HT

J Am Board Fam Med, 2009 Nov-Dec;22(6):686-97.
PMID: 19897698 DOI: 10.3122/jabfm.2009.06.090094

PURPOSE: This article seeks to objectively review the clinical trial evidence to determine whether angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) have special cardiovascular protective effects.
METHODS: An objective review of the clinical trial evidence.
RESULTS: Clinical trials in hypertensive patients comparing ACEI and ARB with other drugs generally showed no difference in the primary cardiovascular outcome (United Kingdom Prospective Diabetes Study Group, Captopril Prevention Project, Swedish Trial in Old Patients with Hypertension 2, Japan Multicenter Investigation for Cardiovascular Diseases-B Randomized Trial, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, Second Australian National Blood Pressure Study Group, Valsartan Antihypertensive Long-Term Use Evaluation). Where the primary, or major secondary, cardiovascular end-point favors one of the treatment arms, it was always the arm with the lower achieved blood pressure that saw the better clinical result as in Losartan Intervention For Endpoint Reduction in Hypertension Study, Captopril Prevention Project, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, and Valsartan Antihypertensive Long-Term Use Evaluation. Trials comparing ACEI or ARB against placebo in patients at high risk of cardiovascular events have not showed a consistent result; cardiovascular outcomes were reduced in Heart Outcomes Prevention Evaluation, European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease, and the Jikei Heart Study, but were not significantly reduced in Perindopril Protection Against Recurrent Stroke Study, Comparison of Arnlodipine vs Enalapril to Limit Occurrences of Thrombosis Trial, Prevention of Events with ACEIs Trial, Telmisartan Randomized Assessment Study in ACE-Intolerant Subjects with Cardiovascular Disease Trial, and Prevention Regimen for Effectively Avoiding Second Strokes Trial. In the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial, combining ACEIs with ARBs in high-risk patients did not reduce cardiovascular or renal outcomes compared with ACEI monotherapy alone. This absence of a reduction in cardiovascular outcome from the ACEI and ARB combination arm is further evidence suggesting that these drugs do not have any special cardiovascular protective effect. This objective review thus shows that the rennin-angiotensin antagonists do not have special cardiovascular protective properties.
CONCLUSION: The key to reducing cardiovascular outcome is to appropriately control blood pressure as well as to treat all other coronary risk factors.
Fulltext Fish oil to prevent heart disease: the evidence and the controversy

Ong HT

Malays Fam Physician, 2006;1(2):65-66.
PMID: 27570590 MyJurnal

Evidence thus far still supports the contention that fish derived omega-3 fatty acids, EPA and DHA, are good for heart patients. But this controversy tells us something about the medical research, and the acquisition and application of medical knowledge. Being scientists, doctors try to perform studies as rigorously as possible with randomised, placebo-controlled trials and using tests of statistical significance. But since the studies are on humans, with all their individual differing habits and inconsistencies, different results are produced by different researchers. And so while medicine is a science, in that the trials are scientifically conducted, the interpretation of the results, and in particular its application for the individual patient, is very much an art. A good doctor, like the good artist, must spend much time, energy and effort sieving through the good from the not so good data before coming out with the correct picture. Only by keeping an unbiased, inquisitive mind can the evidence be reviewed to solve the problem at hand. Almost always, the balance of data will favour a particular stand. In this day when newspapers are full of medical articles, a family physician has to be educated, interested and inquisitive to be a source of accurate and relevant information for the patients.
Fulltext Choice of antihypertensive drug in the diabetic patient

Ong HT, Cheah JS

MedGenMed, 2005;7(2):74.
PMID: 16369452

The hypertensive patient with type 2 diabetes is especially at risk of adverse cardiovascular events. The United Kingdom Prospective Diabetes Study (UKPDS) and Hypertension Optimal Treatment (HOT) studies suggested that treatment to a lower target blood pressure resulted in better prevention of clinical disease in these patients. Most trials comparing antihypertensive drugs have shown only minimal differences between the various agents. The evidence from the trials suggests that diuretics, beta-blockers, calcium channel blockers (CCBs), angiotensin-converting enzyme (ACE) inhibitors, and the angiotensin-receptor antagonists (ARBs) will all successfully reduce adverse clinical events. The largest of the comparative hypertensive drug trials, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), demonstrated that a diuretic has a better hypotensive effect, and was more successful in preventing many aspects of cardiovascular disease compared with CCBs and ACE inhibitors. The importance of good blood pressure control and the general equivalence of antihypertensive drugs were again shown in the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial, which compared an ARB with a CCB. Choice of antihypertensive agent should be individualized and guided by the presence of concomitant clinical disease and the need to protect any specific target organ system in the diabetic hypertensive. Diuretics, being potent hypotensive drugs with clearly demonstrated clinical benefit, should form part of the antihypertensive regimen of most diabetic hypertensives. ACE inhibitors and ARBs are especially useful in preventing nephropathy. Most patients will require a combination of antihypertensive drugs to achieve tight blood pressure control of under 130/80 mm Hg in the diabetic hypertensive. The clinician should concentrate on seeking this lower target blood pressure rather than be excessively concerned about which is the best antihypertensive agent.
Genotyping of hepatitis B virus in Malaysia based on the nucleotide sequence of preS and S genes

Ong HT, Duraisamy G, Kee Peng N, Wen Siang T, Seow HF

Microbes Infect., 2005 Mar;7(3):494-500.
PMID: 15792534

Hepatitis B virus (HBV) has been classified into eight genotypes, designated A-H. These genotypes are known to have distinct geographic distributions. The clinical importance of genotype-related differences in the pathogenicity of HBV has been revealed recently. In Malaysia, the current distribution of HBV remains unclear. The aim of this study was to determine the genotypes and subtypes of HBV by using PCR, followed by DNA sequencing, as well as to analyse the mutations in the immunodominant region of preS and S proteins. The S gene sequence was determined from HBV DNA of four apparently healthy blood donors' sera and three sera from asymptomatic chronic hepatitis B carriers. Of this batch of sera, the preS gene sequence was obtained from HBV DNA from three out of the four blood donors and two out of the three chronic carriers. Due to insufficient sera, we had to resort to using sera from another blood donor to make up for the sixth DNA sequence of the preS gene. Based on the comparative analysis of the preS sequences with the reported sequences in the GenBank database, HBV DNA from two normal carriers was classified as genotype C. Genotype B was assigned to HBV from one blood donor and two hepatitis B chronic carriers, whereas HBV of one chronic carrier was of genotype D. Based on the S gene sequences, HBV from three blood donors was of genotype C, that of one blood donor and one chronic carrier was of genotype B, and the remaining, of genotype D. In the five cases where both preS and S gene sequences were determined, the genotypes assigned based on either the preS or S gene sequences were in concordance. The nature of the deduced amino acid (aa) sequences at positions 125, 127, 134, 143, 159, 161 and 168 of the S gene enabled the classification of these sequences into subtypes, namely, adrq+, adw2 and ayw2. The clustering of our DNA sequences into genotype groups corresponded to their respective subtype, that is, adw2 in genotype B, adrq in genotype C and ayw in genotype D. Analysis of the point mutations revealed that five of the sequences contained aa substitutions at immunodominant epitopes involved in B or/and T cell recognition. In conclusion, despite the low numbers of samples studied, due to budget constraints, these data are still worthwhile reporting, as it is important for the control of HBV infections. In addition, the genotype and mutational data obtained in this study may be useful for designing new treatment regimes for HBV patients.
Fulltext Evidence-based prescribing of statins: a developing world perspective

Ong HT

PLoS Med, 2006 Mar;3(3):e50.
PMID: 16478294
Fulltext Factorial structure, reliability, and construct validity of the Generalized Anxiety Disorder 7-item (GAD-7): Evidence from Malaysia

Pheh KS, Tan CS, Lee KW, Tay KW, Ong HT, Yap SF

PLoS One, 2023;18(5):e0285435.
PMID: 37167230 DOI: 10.1371/journal.pone.0285435

Generalized anxiety disorder (GAD) is one of the most common mental disorders in Malaysia. Psychometrically sound measurements are urgently needed to assess anxiety symptoms. The extensively used Generalized Anxiety Disorder 7-item (GAD-7) is a promising candidate. However, studies on its factorial validity show mixed findings. While the one-factor solution has been replicated in different cultural contexts, some studies found different factorial structures instead. This study aimed to clarify the factorial validity of the English version of the GAD-7 in the Malaysian context. The responses collected from 1272 emerging to older adults in Malaysia were randomly divided into two halves and submitted to exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) respectively. Four acceptable models were explored in EFA ranging from unidimensional factor with 7 items to 3-factor models with 6 items. The four models revealed in EFA and the other competing models found in past studies were then examined and compared using CFA. The 6-item second-order model with a general factor of anxiety and three first-order factors with two items respectively (i.e., GAD-6) showed a more harmonic result and hence, is preferable. Moreover, the GAD-6 and its three subscales also showed satisfactory internal consistency and construct validity. This study uncovers a new and unique factorial structure of the GAD screening tool that fits in the Malaysian context. The scale may reveal GAD symptomatic dimensions that guide clinical interventions.
Fulltext The statin studies: from targeting hypercholesterolaemia to targeting the high-risk patient

Ong HT

QJM, 2005 Aug;98(8):599-614.
PMID: 16006501

The landmark HMG-CoA reductase inhibitor (statin) studies have practical lessons for clinicans. The 4S trial established the importance of treating the hypercholesterolaemic patient with cardiovascular heart disease. Next, WOSCOPS showed the benefit of treating healthy, high-risk hypercholesterolaemic men. CARE, a secondary prevention trial, showed the benefit of treating patients with cholesterol levels within normal limits. This was confirmed by the LIPID trial, another secondary prevention study, which enrolled patients with cholesterol levels 155-271 mg/dl (4-7 mmol/l). The importance of treating patients with established ischaemic heart disease, and those at high risk of developing heart disease, regardless of cholesterol level, was being realized. In the MIRACL trial, hypocholesterolaemic therapy was useful in the setting of an acute coronary syndrome, while the AVERT study showed that aggressive statin therapy is as good as angioplasty in reducing ischaemic events in patients with stable angina. By showing the value of fluvastatin after percutaneous intervention, LIPS confirmed that benefit is a class action of the statins. The HPS randomized over 20 000 patients, and showed beyond doubt the value of statins in reducing cardiovascular events in the high-risk patient. Although PROSPER showed benefit in treating the elderly patients above 70 years, statin therapy in this trial was associated with an increase in cancer incidence. The comparative statin trials, PROVE-IT, REVERSAL, Phase Z of the A to Z, ALLIANCE and TNT, all showed that high-dose statins will better reduce cardiovascular events in the high-risk patient, although the adverse effects of therapy will also be increased. ALLHAT-LLT, ASCOT-LLA and CARDS showed that for statin therapy to demonstrate a significant benefit, hypertensive or diabetic patients must be at sufficiently high risk of cardiovascular events. The emphasis is now on the risk level for developing cardiovascular events, and treatment should target the high-risk group and not the lipid level of the patient. No therapy is free of adverse effect. Treatment of those most at risk will bring the most benefit; treatment of those not at high risk of cardiovascular disease may expose patients who would not benefit much from therapy to its adverse effects.

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