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  1. Zahari Sham SY, C Thambiah S, Samsudin IN, Lim SM
    Malays J Pathol, 2017 Dec;39(3):311-315.
    PMID: 29279596 MyJurnal
    Multiple myeloma is a type of plasma cell dyscrasia, characterised by presence of paraprotein or monoclonal (M)-protein in serum or urine. The M-protein may consist of an intact immunoglobulin, the heavy chain only or the light chain only. The latter, designated as light chain multiple myeloma (LCMM) makes up almost 20% of myelomas. Clinical manifestation is often heralded by hypercalcaemia, renal impairment, normocytic normochromic anaemia and bone lesions, reflecting end-organ damage, collectively known as the acronym CRAB. In particular, free light chain nephrotoxicity accounts for the high prevalence of renal impairment seen in LCMM. This case illustrates a typical presentation of LCMM with focal discussion on its initial and diagnostic, as well as prognostic biochemical investigations.
  2. Cardosa MJ, Noor Sham S, Tio PH, Lim SS
    PMID: 3238470
    A dot enzyme immunoassay (DEIA) was used to determine the levels of antibody to dengue 3 virus in the acute and convalescent sera of febrile patients with a clinical diagnosis of dengue fever or dengue haemorrhagic fever. The antibody titres were compared with titres determined by the haemagglutination inhibition (HI) test. The results of the study showed that, besides being more simple to perform, the DEIA is in order of magnitude more sensitive than the HI test. Furthermore, the data suggest that it is possible to use a single dilution as a cutoff point to predict with reasonable accuracy, if a patient has had a recent dengue infection. The DEIA test for antibodies to dengue virus is an appropriate technology highly suitable for rapid diagnosis and surveillance in developing countries.
  3. Lim SM, Thambiah SC, Zahari Sham SY, Omar R, Hambali Z, Samsudin IN
    Malays J Pathol, 2017 Aug;39(2):135-140.
    PMID: 28866694
    Introduction of high-sensitivity cardiac troponin I (hscTn I) assays for routine clinical use in Malaysia requires determination of the 99(th) percentile upper reference limit (URL) for each assay to suit local context. Hence, this study aimed to determine the 99(th) percentile URL for hscTn I in the Malaysian population. A total of 250 (120 males and 130 females) healthy Malaysian blood donors aged 18 to 60 years old were recruited. Blood samples for hscTn I were measured using Abbott Diagnostics hscTn I assay on Architect i2000sr analyser. The 99(th) percentile was calculated using a non-parametric method and gender specific results were compared. The 99(th) percentile URL for hscTn I for the overall population was 23.7 ng/L, with gender specific values being 29.9 ng/L and 18.6 ng/L for male and female, respectively. Females had significantly lower hscTn I compared to males. This study confirms the use of gender specific 99(th) percentile URL for hscTn I for clinical use in a multi-ethnic Malaysian population.
  4. Sham SF, Ramli AS, Isa MR, Han YW, Whitford DL
    Med J Malaysia, 2018 02;73(1):16-24.
    PMID: 29531198 MyJurnal
    BACKGROUND: The Diabetes Mellitus in the Offspring Questionnaire (DMOQ) assesses the perceptions of Type 2 diabetes mellitus (T2DM) patients on the risk of their offspring developing T2DM and the possibility of intervention to reduce this risk. It has 34 items framed within seven domains. This study aimed to adapt, translate and validate the DMOQ from English into the Malay language.

    METHODS: This was a cross-sectional validation study among 159 T2DM patients attending a public primary care clinic in Selangor. The DMOQ English version underwent adaptation, translation, face validation and field testing to produce the Malay version. Psychometric analysis was performed using Exploratory Factor Analysis, internal consistency and testretest reliability.

    RESULTS: The DMOQ domains were conceptually equivalent between English and Malay language. A total of 13 items and two domains were removed during the validation process (three items during the content validation, three items due to poor factor loadings, five items as they loaded onto two domains which were not interpretable, one item as it did not fit conceptually into the factor it loaded onto and one openended question as it did not fit into the retained domains). Therefore, the final DMOQ Malay version consisted of 21- items within five domains. The Cronbach alpha was 0.714 and the intraclass-correlation coefficient was 0.868.

    CONCLUSION: The DMOQ Malay version is a valid and reliable tool which is consistent over time. It can be used to examine the perception of T2DM patients towards the risk of their offspring developing diabetes and possibility of intervention in Malay-speaking patients.

  5. Ramachandran M, Loi B, Mat Ariff N, Ng OC, Zahari Sham SY, Thambiah SC, et al.
    Malays J Pathol, 2020 Apr;42(1):71-76.
    PMID: 32342933
    INTRODUCTION: Metformin is the first-line pharmacological therapy for type 2 diabetes mellitus (T2DM). Guidelines recommend metformin to be given at reduced dosages for those with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 and omitted in those with eGFR<30 mL/min/1.73m2. Lactic acidosis is a known complication of those on metformin. This study aimed to determine the appropriateness of metformin prescription in T2DM patients with chronic kidney disease (CKD) stages 3-5 in a tertiary centre in Malaysia.

    MATERIALS AND METHODS: A cross-sectional design using retrospective secondary data of T2DM patients on metformin attending nephrology and diabetic clinics in the year 2017. eGFR calculated using the CKD-EPI formula identified those in CKD stage 3-5 defined using the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative criteria. Metformin prescription was considered appropriate when the metformin maximum daily dosage does not exceed 1500 mg in CKD stage 3a and 1000 mg in CKD stage 3b and metformin stopped in CKD stages 4 and 5.

    RESULTS: A total of 143 patients were included. Majority were in the elderly age group (62.9%), male (60.8%) and had concurrent hypertension (85.3%). Median HbA1c was 8.3% (67 mmol/mol) with most patients (88.8%) having HbA1c above 6.5% (48 mmol/ mol). Majority (92.3%) were categorised as stage 3 CKD. Eleven (7.7%) subjects had inappropriate metformin prescription. Seven of nine (78%) subjects in CKD stage 4 were on metformin with a maximum daily dose of 500 mg to1000 mg. Three patients had serum lactate measured.

    CONCLUSION: The majority of CKD patients had appropriate metformin prescription. However, a considerable number of CKD stage 4 patients continued to be on metformin. The many benefits of metformin may be a reason why it is still continued against recommendations. Only three patients had lactate measured which, although may suggest that lactic acidosis is not a common occurrence, the potential for metformin-associated lactic acidosis especially in those at risk should be considered.

  6. Thambiah CS, Mohamed Pesri NA, Mazalan N, Samsudin IN, Mohamad Ismuddin S, Appannah G, et al.
    Malays J Pathol, 2020 Aug;42(2):215-225.
    PMID: 32860374
    INTRODUCTION: Dyslipidaemia is a recognised conventional risk factor for cardiovascular disease (CVD). However, even when traditional lipid parameters are normal, CVD risk can exist. Small dense lowdensity lipoprotein cholesterol (sdLDL) has appeared as a significant risk marker for CVD. This study aimed to determine the prevalence and associated factors of atherogenic lipoprotein Pattern B in the Malaysian population.

    MATERIALS AND METHODS: This cross-sectional study included 150 subjects aged 30 years and above who attended a health screening in a Malaysian tertiary institution. Sociodemographics, clinical characteristics and laboratory parameters (lipids, glucose, and sdLDL) were obtained. Lipoprotein subfraction was analysed using the polyacrylamide gel electrophoresis method.

    RESULTS: Malays and females made up the majority of subjects and the median age was 37 years. Normolipidaemic Pattern B was significantly higher in women (p=0.008). Significant independent predictors of Pattern B were gender (p=0.02), race (p=0.01), body mass index (BMI) [p=0.02] and lipid status (p=0.01). Triglyceride was the only independent predictor of sdLDL (p=0.001).

    CONCLUSION: The prevalence of Pattern B of 33% in this study was comparatively high, of which 6.7% were normolipidaemic. Chinese males with dyslipidaemia and increased BMI independently predicted Pattern B. Differences in triglyceride levels alone among these ethnic groups do not fully explain the differences in the prevalence of Pattern B although it was the only lipid parameter to independently predict sdLDL. Individuals with atherogenic normolipidaemia are at greater risk for a CVD event as they are not included in the protective measures of primary CVD prevention.

  7. Choo JE, Samsudin IN, Mat Salleh MJ, Zahari Sham SY, Thambiah SC
    Malays J Pathol, 2020 Dec;42(3):433-437.
    PMID: 33361725
    INTRODUCTION: Salivary cortisol is used as an indicator of stress level and a recommended screening test for Cushing syndrome. The normal reference interval for salivary cortisol is dependent on the analytical methodology and the population studied and hence, establishment of a local population-based reference interval is recommended.

    MATERIALS AND METHODS: A total of 129 healthy blood donors and staffs of Penang General Hospital were recruited from June 2018-May 2019. Paired (morning and late-night) saliva samples were collected from individuals aged between 18 and 60 years old with no history of chronic medical illness. Salivary cortisol was assayed using electrochemiluminescence immunoassay technique. Non-parametric statistics were used for calculation of reference interval and 90% confidence intervals (90% CIs).

    RESULTS: The reference interval for morning and latenight salivary cortisol was 2.09 - 22.63 nmol/L and <12.00 nmol/L, respectively.

    CONCLUSION: The locally-derived adult reference intervals for morning and late-night salivary cortisol concentration was determined and varied with previous studies emphasising the need in establishing individual laboratory reference interval.

  8. Bahrom NH, Ramli AS, Isa MR, Baharudin N, Badlishah-Sham SF, Mohamed-Yassin MS, et al.
    Malays Fam Physician, 2020;15(3):22-34.
    PMID: 33329860
    Introduction: The Patient Activation Measure (PAM) is one of the most extensively used, widely translated, and tested instruments worldwide in measuring patient activation levels in self-management. This study aimed to determine the validity and reliability of the PAM-13 Malay version among patients with Metabolic Syndrome (MetS) attending a primary care clinic.
    Methods: This work is a cross-sectional validation study among patients with MetS attending a university primary care clinic in Selangor. The PAM-13 Malay version underwent a validation process and field testing. Psychometric properties were examined using principal component analysis (PCA) with varimax rotation, scree plot, Monte Carlo simulation, internal consistency, and test-retest reliability analyses.
    Results: The content of the PAM-13 Malay version and the original version were conceptually equivalent. The questionnaire was refined after face validation by 10 patients with MetS. The refined version was then field-tested among 130 participants (response rate 89.7%). The Kaiser-Meyer-Olkin test was 0.767, and Bartlett's test of sphericity was ≤0.001, indicating sampling adequacy. Two factors were identified and labeled as (1) Passive and Building Knowledge, and (2) Taking Action and Maintaining Behavior. These labels were chosen as they were conceptually consistent with the items representing the levels of activation in PAM-13. The validated PAM-13 Malay version consisted of 13 items, framed into two domains. The overall Cronbach's α was 0.79, and the intraclass correlation coefficient was 0.45.
    Conclusions: The PAM-13 Malay version is valid, reliable, and fairly stable over time. This questionnaire can be used to evaluate the levels of activation among patients with MetS in primary care in Malaysia.
    Study site: Universiti Teknologi MARA (UiTM) primary care clinic, Sungai Buloh, Selangor, Malaysia
  9. Zahari Sham SY, Hanif E, Thambiah SC, Samsudin IN, Mohd Noor S, Osman M, et al.
    Malays J Pathol, 2021 04;43(1):33-40.
    PMID: 33903303
    INTRODUCTION: Cardiovascular disease (CVD) remains the leading cause of death in Malaysia. Identification of asymptomatic at-risk individuals is often achieved by means of a risk prediction algorithm. Traditional CVD risk factors and their associated algorithms are, however, limited by residual CVD risk. High sensitivity C-reactive protein (hsCRP) has emerged as a novel CVD risk factor. This study aimed to evaluate hsCRP as an adjunct CVD risk marker among the adult Malaysian population by determining its correlation with the Framingham Risk Score (FRS). Comparison analyses were done according to sociodemographic, clinical and laboratory factors and between subjects with and without Metabolic Syndrome (MetS).

    METHOD: This cross-sectional study involved eighty-three (n=83) adults attending a health screening program at Universiti Putra Malaysia (UPM). Demographic data, anthropometric measurements and blood samples for fasting blood glucose (FBG), fasting lipid profile (FSL), glycated haemoglobin (HbA1c) and hsCRP were taken. Respondents were grouped according to FRS and the Joint Interim Statement into 10-year CVD risk categories (low, intermediate and high) and MetS, respectively.

    RESULTS: hsCRP was significantly increased in patients with high body mass index (BMI) (p=0.001), at-risk waist circumference (WC) (p=0.001) and MetS (p=0.009). Spearman's correlation coefficient showed a significant positive correlation between hsCRP level and total FRS score (r=0.26, p<0.05) and HDL-C score (r=0.22, p<0.05).

    CONCLUSION: The significant difference of hsCRP levels across obesity levels and MetS with its modest correlation with FRS scores supported the adjunctive role of hsCRP in CVD risk prediction, most likely capturing the inflammatory pathological aspect and thus partly accounting for the residual CVD risk.

  10. Zainal-Abidin ANI, Miptah HN, Ariffin F, Razali S, Badlishah-Sham SF
    Heliyon, 2024 Feb 29;10(4):e25740.
    PMID: 38380003 DOI: 10.1016/j.heliyon.2024.e25740
    BACKGROUND: As young People Living with HIV (PLHIV) will need to take antiretroviral therapy (ART) for life, there is a need to understand their coping mechanisms in living with the disease. Lack of coping mechanisms leads to poor medication adherence and hospital follow-up, poor health outcomes and shortened life expectancy.

    OBJECTIVES: This study aimed to determine the pattern of coping mechanisms in young PLHIV and its association with medication adherence.

    METHODS: This study was a cross-sectional study amongst young PLHIV patients (aged 20-39 years old) attending two HIV clinics in Klang Valley. Data was collected between February to August 2022. The pattern of coping strategies was assessed using the 28-item Brief Coping Orientation to Problems Experienced (COPE) questionnaire in English and Malay language, which was validated and found to have good internal consistency. Self-reported medication adherence was measured using the one-item Medical Outcomes Study (MOS) Specific Adherence Scale. Statistical analysis included descriptive statistics, single and multiple logistic regression.

    RESULTS: A total of 395 respondents were recruited for the study. The mean scores for each coping mechanism were: 1) problem-focused coping 2.98 (SD 0.62), 2) emotion-focused coping 2.40 (SD 0.48), 3) dysfunctional coping 1.84 (SD 0.44) and 4) religion/spirituality coping 3.07 (SD 0.97). The majority of the respondents (66.8%) were adherent to their ART. Respondents who had a longer duration of medication [OR:1.014 (95% CI: 1.002,1.026)] and those who adopted less religion/spirituality coping mechanisms [OR: 0.495 (95% CI:0.246, 0.997)] were found to be significantly associated with medication adherence.

    CONCLUSION: This study revealed an overall medication adherence rate of 66.8%. Patients with longer ART duration and who adopted less religion or spirituality coping had better medication adherence. These study findings provide input into the design of intervention by clinicians and healthcare policy makers for young PLHIV in clinical practice.

  11. Thambiah SC, Samsudin IN, George E, Zahari Sham SY, Lee HM, Muhamad MA, et al.
    Malays J Pathol, 2016 Aug;38(2):123-30.
    PMID: 27568669 MyJurnal
    The risk of coronary heart disease (CHD) is dramatically increased in diabetic patients due to their atherogenic lipid profile. The severity of CHD in diabetic patients has been found to be directly associated with glycated haemoglobin (HbA1c). According to the Malaysian Clinical Practice Guidelines on diabetes mellitus (DM), HbA1c level less than 6.5% reduces the risk of microvascular and macrovascular complications. Hence, this study aimed to determine the relationship between dyslipidaemia and glycaemic status in patients with type 2 DM (T2DM) patients in Hospital Putrajaya, a tertiary endocrine centre in Malaysia. This was a cross sectional, retrospective study of 214 T2DM patients with dyslipidaemia who had visited the endocrine clinic between January 2009 and December 2012. Significant correlations were found between fasting blood glucose (FBG) and HbA1c with total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL), non-high density lipoprotein cholesterol (non-HDL), LDL/HDL ratio and TC/HDL ratio; greater correlation being with HbA1c than FBG. In patients with HbA1c ≥ 6.5%, TC, TG, non-HDL and TC/HDL ratio were significantly higher than in patients with HbA1c < 6.5%. Non-HDL, LDL/HDL ratio, TC/HDL ratio and HbA1c were significantly lower in patients on statin treatment than nontreated patients (p<0.05). This significant association between glycaemic status and dyslipidaemia emphasises the additional possible use of HbA1c as a biomarker for dyslipidaemia as well as a potential indirect predictor of cardiovascular disease (CVD) risk in T2DM patients.
  12. Mohamad Ismuddin S, Thambiah SC, Appannah G, Samsudin IN, Md Said S, Yeap SS, et al.
    Malays J Pathol, 2022 Dec;44(3):477-490.
    PMID: 36591715
    INTRODUCTION: Cardiovascular disease and osteoporosis (OP) have been shown to have similar risk factors but studies have demonstrated contradictory results with regards to their associations. This study evaluated relationships between bone characteristics and cardiovascular risk factors among adults in selected urban areas in Malaysia.

    MATERIALS AND METHODS: A cross-sectional study was performed involving 331 subjects between 45-90 years recruited at a health screening programme. Sociodemographic and clinical characteristics were recorded. Biochemical analyses on fasting blood samples and dual energy X-ray absorptiometry scan to determine bone mineral density (BMD) were performed.

    RESULTS: Increased waist circumference (WC) was protective for abnormal BMD status (osteopenia and OP). Males with increased high-density lipoprotein cholesterol (HDL) were more likely to be osteoporotic. WC, fasting blood glucose (FBG) and triglyceride (TG) were positively associated with BMD at all sites but was gender specific. In contrast, WC was negatively associated with trabecular bone score (TBS) for females but this association became attenuated when adjusted for fat percentage. HDL and MetS were negatively and positively associated with BMD, respectively in males.

    CONCLUSION: The cardiovascular risk factors of raised WC, FBG, TG and low HDL were significantly associated with increased BMD with skeletal site and gender specific differences after adjusting for confounders. However, a higher WC was associated with a weaker skeletal microstructure reflected by lower TBS in females driven by fat percentage. A higher BMD was demonstrated among MetS individuals. These findings suggest that adiposity may have a protective effect on BMD.

  13. GBD 2023 LDL Cholesterol Collaborators, Razo C, DeCleene NK, Johnson CO, Stark BA, LeGrand K, et al.
    JAMA, 2026 Aug 25;336(8):673-698.
    PMID: 42525403 DOI: 10.1001/jama.2026.8628
    IMPORTANCE: Elevated low-density lipoprotein cholesterol (LDL-C) is a modifiable risk factor for cardiovascular disease, the leading cause of premature death worldwide. Assessing the LDL-C-related burden is critical for guiding prevention and treatment strategies.

    OBJECTIVES: To estimate the global, regional, and national burden of ischemic heart disease and ischemic stroke attributable to elevated LDL-C (relative to 35-54 mg/dL) from 1990 to 2023 and to quantify the contributions of population growth, aging, risk-deleted burden, and exposure changes to burden trends.

    DESIGN, SETTING, AND POPULATION: This comparative risk assessment, part of the Global Burden of Disease Study 2023, estimated population-level LDL-C exposure and associated health loss in 204 countries and territories. Mean LDL-C levels were estimated using spatiotemporal gaussian process regression based on 806 studies across 161 countries. Relative risks were derived from meta-analyses of 38 randomized clinical trials. Population-attributable fractions for deaths and disability-adjusted life-years (DALYs) were estimated by age and sex for adults aged 25 years or older from 1990 to 2023, with 95% uncertainty intervals.

    EXPOSURE: Population-level LDL-C concentrations.

    MAIN OUTCOMES AND MEASURES: Population-attributable fractions, counts, and rates (all ages and age standardized per 100 000) of LDL-C-attributable deaths and DALYs from ischemic heart disease and ischemic stroke, with uncertainty intervals.

    RESULTS: In 2023, elevated LDL-C accounted for 3.6 million deaths (95% uncertainty interval, 2.2-5.4 million; 6.0% of global mortality) and 90.7 million DALYs (95% uncertainty interval, 58.9-123.3 million; 3.2% of DALYs). Although global all-ages rates remained stable, age-standardized death and DALY rates decreased by 45.6% and 39.5%, respectively, since 1990. In 2023, age-standardized LDL-C-attributable DALY rates were highest in Eastern Europe and lowest in high-income Asia-Pacific. One-third of the global LDL-C burden occurred in India and China. Population growth and aging drove the increasing burden, with notable regional disparities in LDL-C exposure and risk-deleted DALY rates shifting toward middle-sociodemographic settings.

    CONCLUSIONS AND RELEVANCE: Despite declining age-standardized rates, the absolute LDL-C burden has increased since 1990 due to demographic changes and has shifted toward middle-sociodemographic countries. Measurement and surveillance gaps persist. Strengthened prevention, diagnosis, and treatment access strategies are essential to mitigate the health burden of LDL-C.

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