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  1. Fulltext Genetic researches among malaysian familial hypercholesterolaemic population
    Al-Khateeb, A, Al-Talib, H
    JUMMEC, 2016;19(2):1-11.
    MyJurnal
    Background:
    Familial hypercholesterolaemia (FH) is one of the most frequent inherited metabolic disorders that can lead
    to a risk of premature cardiovascular disease. Publications on FH are mainly from western patients as there is
    little research on Asians, including Malaysians. The aim of this review is to provide an up-to- date information
    on Malaysian studies on FH genotyping and its relation to the phenotype of the affected patients.
    Method:
    A search was conducted for data from online databases on FH in Malaysia.
    Results:
    The mutation spectrum for FH among Malaysian patients was extremely broad. The gene variants were located
    mainly in the low-density lipoprotein receptor (LDLR) and apolipoprotein B-100 (APOB-100) genes rather than
    in the proprotein convertase subtilisin kexin type 9 (PCSK9) gene. The exon 9 and 14 were the hotspots in the
    LDLR gene. The most frequent mutation was p.Cys255Ser, at 12.5%, followed by p.Arg471Gly, at 11%, and the
    most common single nucleotide polymorphism (SNP) was c.1060+7 T>C at 11.7%. The LDLR gene variants were
    more common compared to the APOB-100 gene variants, while variants in the PCSK9 gene were very few.
    Phenotype-genotype associations were identified. Subjects with LDLR and APOB-100 genes mutations had a
    higher frequency of cardiovascular disease, a family history of hyperlipidaemia and tendon xanthoma and a
    higher low-density lipoprotein cholesterol (LDL-C) level than non-carriers.
    Conclusion:
    Research on Malaysian familial hypercholesterolaemic patients by individual groups is encouraging. However,
    more extensive molecular studies on FH on a national scale, with a screening of the disease-causing mutations
    together with a comprehensive genotype-phenotype association study, can lead to a better outcome for
    patients with the disease.
  2. Fulltext Intestinal parasitic diarrhea among children in Baghdad--Iraq
    AL-Kubaisy W, AL-Talib H, Al-khateeb A, Shanshal MM
    Trop Biomed, 2014 Sep;31(3):499-506.
    PMID: 25382477
    Parasitic diarrhea among children is a significant health problem worldwide. This cross sectional study described the burden of parasitic diarrhea among children. The objectives of this study were to evaluate the impact of risk factors on the parasitic diarrhea, and to determine the parasitic profile among children in Baghdad-Iraq, during the period extending from September 2003 to June 2004. A total number of 2033 cases were included in the study. The estimated prevalence rate of parasitic diarrhea was 22%. We identified the following major diarrhea determinants were large households size, residential location, water source, low socioeconomic status, and low parent education. Giardia lamblia was found to be the most prevalent parasite with an infection rate of 45.54% followed by Entamoeba histolytica 23.44%, Enterobius vermicularis 12.7%, Hymenolepis nana 9.82%, Trichuris trichiura 5.4%, and Ascaris lumbricoides 2.2%. In conclusion, this study demonstrates that poor sanitation, inadequate environmental conditions, and low socioeconomic status are the main determining factors that predispose children to parasitic diarrhea. Mass deworming programs are recommended for school children, as this population is easily accessible.
  3. Fulltext Efficacy and safety of superficial chemical peeling in treatment of active acne vulgaris
    Al-Talib H, Al-Khateeb A, Hameed A, Murugaiah C
    An Bras Dermatol, 2017 5 26;92(2):212-216.
    PMID: 28538881 DOI: 10.1590/abd1806-4841.20175273
    Acne vulgaris is an extremely common condition affecting the pilosebaceous unit of the skin and characterized by presence of comedones, papules, pustules, nodules, cysts, which might result in permanent scars. Acne vulgaris commonly involve adolescents and young age groups. Active acne vulgaris is usually associated with several complications like hyper or hypopigmentation, scar formation and skin disfigurement. Previous studies have targeted the efficiency and safety of local and systemic agents in the treatment of active acne vulgaris. Superficial chemical peeling is a skin-wounding procedure which might cause some potentially undesirable adverse events. This study was conducted to review the efficacy and safety of superficial chemical peeling in the treatment of active acne vulgaris. It is a structured review of an earlier seven articles meeting the inclusion and exclusion criteria. The clinical assessments were based on pretreatment and post-treatment comparisons and the role of superficial chemical peeling in reduction of papules, pustules and comedones in active acne vulgaris. This study showed that almost all patients tolerated well the chemical peeling procedures despite a mild discomfort, burning, irritation and erythema have been reported; also the incidence of major adverse events was very low and easily manageable. In conclusion, chemical peeling with glycolic acid is a well-tolerated and safe treatment modality in active acne vulgaris while salicylic acid peels is a more convenient for treatment of darker skin patients and it showed significant and earlier improvement than glycolic acid.
  4. Fulltext Rapid detection of methicillin-resistant Staphylococcus aureus by a newly developed dry reagent-based polymerase chain reaction assay
    Al-Talib H, Yean CY, Al-Khateeb A, Hasan H, Ravichandran M
    J Microbiol Immunol Infect, 2014 Dec;47(6):484-90.
    PMID: 23927820 DOI: 10.1016/j.jmii.2013.06.004
    Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen responsible for significant numbers of nosocomial and community-acquired infections worldwide. Molecular diagnosis for MRSA nasal carriers is increasingly important for rapid detection and screening of MRSA colonization because the conventional methods are time consuming and labor intensive. However, conventional polymerase chain reaction (PCR) tests still require cold-chain storage as well as trained personnel, which makes them unsuitable for rapid high-throughput analysis. The aim of this study was to develop a thermostabilized PCR assay for MRSA in a ready-to-use form that requires no cold chain.
  5. Lipid profile parameters in Malaysian dyslipidemic patients
    Al-Khateeb A, Mohamed MS, Imran K, Ibrahim S, Zilfalil BA, Yusof Z
    Kobe J Med Sci, 2011;57(2):E38-48.
    PMID: 22926072
    The importance of serum lipids as cardiovascular risk factors is well recognized. However, most published studies have focused on western countries. The present study aimed to describe and analyze the lipid profile parameters in Malaysian dyslipidemic patients, and to identify concomitant clinical problems and risk factors associated with cardiovascular disease (CVD) among such patients.
  6. Comparative evaluation of five culture media with triplex PCR assay for detection of methicillin-resistant Staphylococcus aureus
    Al-Talib H, Yean CY, Al-khateeb A, Singh KK, Hasan H, Al-Jashamy K, et al.
    Curr Microbiol, 2010 Jul;61(1):1-6.
    PMID: 20033170 DOI: 10.1007/s00284-009-9567-8
    The emergence of methicillin-resistant Staphylococcus aureus (MRSA) is responsible for nosocomial and community-acquired infections. Hence, rapid and accurate laboratory diagnosis of MRSA is a vital constituent of control measures. The present study evaluated five different methods for the identification of MRSA. A total of 207 S. aureus clinical isolates that consisted of 89 MRSA and 118 methicillin-susceptible S. aureus (MSSA) strains confirmed by PCR were tested. MRSA strains were evaluated by five different methods: chromogenic MRSA agar (CMRSA), oxacillin resistance screening agar base (ORSAB), mannitol salt oxacillin agar (MSO), mannitol salt cefoxitin agar with two different concentrations of cefoxitin [4 microg/ml (MSC-4) and 6 microg/ml (MSC-6)]. The results of the different methods were compared to mecA PCR as the gold standard. MSC-6 showed only six false-positive MRSA in comparison with PCR. The sensitivities and specificities of MSC-6, MSC-4, MSO-4, ORSAB, and CMRSA were as follows: 98.9/94.9%, 100/83.1%, 89.9/87.3%, 97.8/96.6%, and 95.5/94.9%, respectively. In comparison with PCR, it was found that both MSC-6 and ORSAB were relatively the least expensive screening tests ($0.70 and $1.00, respectively). In conclusion, all methods were comparable, but MSC-6 was the least expensive medium for MRSA screening.
  7. Fulltext Phenotype-genotype analyses of clinically diagnosed Malaysian familial hypercholestrolemic patients
    Al-Khateeb A, Al-Talib H, Mohamed MS, Yusof Z, Zilfalil BA
    Adv Clin Exp Med, 2013 Jan-Feb;22(1):57-67.
    PMID: 23468263
    BACKGROUND: Familial hypercholesterolemia and familial defective apo lipoprotein B are genetic disorders caused by defects in the low-density lipoprotein receptor gene and apo lipoprotein B 100 genes, respectively. The clinical phenotype of both diseases is characterized by increased plasma levels of total cholesterol and low density lipoprotein cholesterol, tendinous xanthomata, and premature coronary heart disease.
    OBJECTIVES: The aim of this study is to perform an association study between different gene sequence variants in low-density lipoprotein and apo lipoprotein B 100 genes to the clinical finding and lipid profile parameters of the study subjects.
    MATERIAL AND METHODS: A group of 164 familial hypercholesterolemic patients were recruited. The promoter region, exon 2-15 of the low density lipoprotein gene and parts of exon 26 and 29 of apo lipoprotein B 100 gene were screened by Denaturating Gradient High Performance Liquid Chromatography.
    RESULTS: For the apo lipoprotein B 100 gene, those with apo lipoprotein B 100 gene mutation have a significantly higher frequency of cardiovascular disease (P = 0.045), higher low density lipoprotein cholesterol and total cholesterol: high density lipoprotein cholesterol ratio than those without mutation (P = 0.03 and 0.02, respectively). For the low density lipoprotein gene defect those with frame shift mutation group showed the worst clinical presentation in terms of low density lipoprotein cholesterol level and cardiovascular frequency.
    CONCLUSIONS: There was a statistically significant association between mutations of low density lipoprotein gene and apo lipoprotein B 100 genes and history of cardiovascular disease, younger age of presentation, family history of hyperlipidemia, tendon xanthoma and low density lipoprotein cholesterol level.
    Study site: Cardiology Clinic, Hospital Universiti Sains Malaysia (HUSM), Kelantan, Malaysia
  8. A successful pregnancy outcome of homozygous familial hypercholesterolaemia patient on statin therapy
    Mohd Kasim NA, Al-Khateeb A, Chua YA, Sanusi AR, Mohd Nawawi H
    Malays J Pathol, 2021 Apr;43(1):87-93.
    PMID: 33903311
    Homozygous familial hypercholesterolaemia (HoFH) is a rare genetic disorder of lipoprotein metabolism mainly due to mutation of the low-density lipoprotein (LDL)-receptor gene (LDLR). It is a life-threatening disease that causes accelerated, multi-vessel atherosclerosis presented in early childhood. Pregnancy in HoFH may pose early coronary morbidity and mortality to both the foetus and mother. The combination of HoFH and pregnancy can be a fatal condition. While statins are very effective in lowering low-density lipoprotein cholesterol (LDL-C) levels, they are generally contraindicated during pregnancy, thus their use during pregnancy is uncommon. On the other hand, lipid apheresis (LA) has turned into an effective treatment to control cholesterol level amid pregnancy. However, the procedure is not widely available in our region. To date, there are scarcely documented case reports of HoFH in pregnancy in which the majority of them underwent LA to keep LDL-C at a low level. We report a rare case of successful pregnancy outcome of HoFH patient treated with lipid-lowering drugs including statin without LA therapy. Apart from that, we also discussed the genetic findings of the proband and all screened family members in which to the best of our knowledge, the first study using the whole-exome sequencing technique to identify the causative gene mutations for familial hypercholesterolaemia among the Malaysian population.
  9. Fulltext A pentaplex PCR assay for the rapid detection of methicillin-resistant Staphylococcus aureus and Panton-Valentine Leucocidin
    Al-Talib H, Yean CY, Al-Khateeb A, Hassan H, Singh KK, Al-Jashamy K, et al.
    BMC Microbiol, 2009;9:113.
    PMID: 19476638 DOI: 10.1186/1471-2180-9-113
    Staphylococcus aureus is a major human pathogen, especially methicillin-resistant S. aureus (MRSA), which causes a wide range of hospital and community-acquired infections worldwide. Conventional testing for detection of MRSA takes 2-5 days to yield complete information of the organism and its antibiotic sensitivity pattern.
  10. Development of an Optimized Tetra-Amplification Refractory Mutation System PCR for Detection of 12 Pathogenic Familial Hypercholesterolemia Variants in the Asian Population
    Rosman N, Nawawi HM, Al-Khateeb A, Chua YA, Chua AL
    J Mol Diagn, 2022 02;24(2):120-130.
    PMID: 35074074 DOI: 10.1016/j.jmoldx.2021.10.006
    Early detection of genetic diseases such as familial hypercholesterolemia (FH), and the confirmation of related pathogenic variants, are crucial in reducing the risk for premature coronary artery disease. Currently, next-generation sequencing is used for detecting FH-related candidate genes but is expensive and time-consuming. There is a lack of kits suitable for the detection of the common FH-related variants in the Asia-Pacific region. Thus, this study addressed that need with the development of an optimized tetra-amplification mutation system (T-ARMS) PCR-based assay for the detection of 12 pathogenic variants of FH in the Asian population. The two important parameters for T-ARMS PCR assay performance-annealing temperature and the ratio of outer/inner primer concentrations-were optimized in this study. The optimal annealing temperature of all 12 T-ARMS PCR reactions was 64.6°C. The ideal ratios of outer/inner primer concentrations with each pathogenic variant were: A1, 1:2; A2, 1:4; L1, 1:10; L2, 1:1; L3, 1:2; L4, 1:8; L5, 1:1; L6, 1:2; L7, 1:8; L8, 1:8; L9, 1:2; and L10, 1:8. The lowest limit of detection using DNA extracted from patients was 0.1 ng. The present article highlights the beneficial findings on T-ARMS PCR as part of the development of a PCR-based detection kit for use in detecting FH in economically developing countries in Asia with a greater prevalence of FH.
  11. Fulltext Analysis of sequence variations in low-density lipoprotein receptor gene among Malaysian patients with familial hypercholesterolemia
    Al-Khateeb A, Zahri MK, Mohamed MS, Sasongko TH, Ibrahim S, Yusof Z, et al.
    BMC Med Genet, 2011;12:40.
    PMID: 21418584 DOI: 10.1186/1471-2350-12-40
    Familial hypercholesterolemia is a genetic disorder mainly caused by defects in the low-density lipoprotein receptor gene. Few and limited analyses of familial hypercholesterolemia have been performed in Malaysia, and the underlying mutations therefore remain largely unknown.We studied a group of 154 unrelated FH patients from a northern area of Malaysia (Kelantan). The promoter region and exons 2-15 of the LDLR gene were screened by denaturing high-performance liquid chromatography to detect short deletions and nucleotide substitutions, and by multiplex ligation-dependent probe amplification to detect large rearrangements.
  12. Fulltext Undertreatment and Underachievement of LDL-C Target among Individuals with High and Very High Cardiovascular Risk in the Malaysian Community
    Razman AZ, Baharudin N, Mohd Kasim NA, Al-Khateeb A, Ismail Z, Nawawi H, et al.
    Healthcare (Basel), 2022 Dec 05;10(12).
    PMID: 36553972 DOI: 10.3390/healthcare10122448
    Dyslipidaemia is a major cause of morbidity and mortality. The aims of this study are to determine the prevalence of dyslipidaemia subtypes, the proportions of lipid-lowering therapy (LLT) use, and the achievement of low-density lipoprotein cholesterol (LDL-C) treatment targets for high-risk (HR) and very high-risk (VHR) Malaysians. This cross-sectional study involves 5279 participants across 11 states in Malaysia. The data were obtained through a standardised questionnaire, anthropometric measurements, venous glucose and lipid profile. The participants with existing cardiovascular disease (CVD) or diabetes with at least one of the other major risk factors (smoking, hypertension or dyslipidaemia) were grouped into the VHR category. Other participants were risk-categorised using the Framingham General CVD Risk Score (FRS-CVD). The prevalence of elevated LDL-C, LLT use and LDL-C target were set according to respective risk categories. Pearson's chi-squared test was used to test the difference in the proportions. The mean ± standard deviation (SD) age was 41.1 ± 14.8 years, and 62.2% (3283/5279) of the group were females. Within the participant group, 51.5% were found to have elevated total cholesterol, 28.8% had low HDL-C, and 33.8% had high triglyceride. As for elevated LDL-C, 9.8% were in VHR, 8.6% in HR, 5.8% in MR and 34.9% in LR categories. Among the VHR group, 75.8% were not on LLT, and only 15.9% achieved the LDL-C target. As for the HR category, 87.7% were not on LLT, and only 16.1% achieved the LDL-C target. Dyslipidaemia is highly prevalent among Malaysians. The majority of VHR and HR participants were not on LLT and did not achieve LDL-C treatment targets. Proactive programs are warranted to combat dyslipidaemia-associated CVD events in these groups.
  13. Fulltext Low-density lipoprotein cholesterol goal attainment among Malaysian dyslipidemic patients
    Al-Khateeb A, Mohamed MS, Imran K, Ibrahim S, Zilfalill BA, Yusof Z
    Southeast Asian J Trop Med Public Health, 2011 Mar;42(2):388-94.
    PMID: 21710862
    The aim of the present study was to evaluate Malaysian dyslipidemic patient treatment practices and outcomes. Factors contributing to success in reaching treatment goal were determined. A retrospective review of the records of dyslipidemic patients who attended the Universiti Sains Malaysia Hospital in 2007 was conducted. All the patients were receiving standard recommended doses of statins. Records were analysed for 890 patients. Patients were divided into three categories: 384 patients (43.1%) had coronary heart disease or coronary heart disease risk equivalents, 216 patients (24.3%) had moderate risk for coronary heart disease and 290 patients (32.6%) had low risk. Statins were the most commonly prescribed drug group (92%), of which atorvastatin was the most commonly prescribed drug (50.6%). The overall success rate for reaching goal was 64.2%. The percentages of patients achieving low-density lipoprotein cholesterol targets in the coronary heart disease and coronary heart disease risk equivalents, moderate, and low-risk groups were 50.5, 66.7, and 80.3%, respectively (p < 0.001). Multiple logistic regression showed achievement of therapeutic goal declined with increasing risk group. The baseline low-density lipoprotein cholesterol value was inversely related to therapeutic goal attainment. An inadequate proportion of dyslipidemic patients achieved the National Cholesterol Education Program therapeutic goals for low-density lipoprotein cholesterol, especially those in the coronary heart disease and coronary heart disease risk equivalent group. The achievement of this goal was dependent on baseline low-density lipoprotein cholesterol levels.
  14. Fulltext Genetic Spectrum of Familial Hypercholesterolaemia in the Malaysian Community: Identification of Pathogenic Gene Variants Using Targeted Next-Generation Sequencing
    Razman AZ, Chua YA, Mohd Kasim NA, Al-Khateeb A, Sheikh Abdul Kadir SH, Jusoh SA, et al.
    Int J Mol Sci, 2022 Nov 29;23(23).
    PMID: 36499307 DOI: 10.3390/ijms232314971
    Familial hypercholesterolaemia (FH) is caused by mutations in lipid metabolism genes, predominantly in low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), proprotein convertase subtilisin/kexin-type 9 (PCSK9) and LDL receptor adaptor protein 1 (LDLRAP1). The prevalence of genetically confirmed FH and the detection rate of pathogenic variants (PV) amongst clinically diagnosed patients is not well established. Targeted next-generation sequencing of LDLR, APOB, PCSK9 and LDLRAP1 was performed on 372 clinically diagnosed Malaysian FH subjects. Out of 361 variants identified, 40 of them were PV (18 = LDLR, 15 = APOB, 5 = PCSK9 and 2 = LDLRAP1). The majority of the PV were LDLR and APOB, where the frequency of both PV were almost similar. About 39% of clinically diagnosed FH have PV in PCSK9 alone and two novel variants of PCSK9 were identified in this study, which have not been described in Malaysia and globally. The prevalence of genetically confirmed potential FH in the community was 1:427, with a detection rate of PV at 0.2% (12/5130). About one-fourth of clinically diagnosed FH in the Malaysian community can be genetically confirmed. The detection rate of genetic confirmation is similar between potential and possible FH groups, suggesting a need for genetic confirmation in index cases from both groups. Clinical and genetic confirmation of FH index cases in the community may enhance the early detection of affected family members through family cascade screening.
  15. Fulltext Coronary risk factor profiles according to different age categories in premature coronary artery disease patients who have undergone percutaneous coronary intervention
    Nazli SA, Rosman A, Mohd Kasim NA, Al-Khateeb A, Ul-Saufie AZ, Md Radzi AB, et al.
    Sci Rep, 2024 Jul 03;14(1):15326.
    PMID: 38961082 DOI: 10.1038/s41598-024-53539-6
    Many studies have investigated the coronary risk factors (CRFs) among premature coronary artery disease (PCAD) patients. However, reports on the proportion and CRFs of PCAD according to different age cut-offs for PCAD is globally under-reported. This study aimed to determine the proportion of PCAD patients and analyse the significant CRFs according to different age cut-offs among percutaneous coronary intervention (PCI)-treated patients. Patients who underwent PCI between 2007 and 2018 in two cardiology centres were included (n = 29,241) and were grouped into four age cut-off groups that defines PCAD: (A) Males/females: 
  16. Fulltext The Malaysia DREEM: perceptions of medical students about the learning environment in a medical school in Malaysia
    Al-Naggar RA, Abdulghani M, Osman MT, Al-Kubaisy W, Daher AM, Nor Aripin KN, et al.
    Adv Med Educ Pract, 2014;5:177-84.
    PMID: 24959093 DOI: 10.2147/AMEP.S61805
    BACKGROUND:
    Students' perceptions of their learning environment, by defining its strengths and weaknesses, are important for continuous improvement of the educational environments and curriculum. Therefore, the aim of this study was to explore students' perceptions of their learning environment, among medical students in Malaysia. Various aspects of the education environment were compared between year levels and sex.

    METHODS:
    This cross-sectional study was conducted at the Management and Science University, Shah Alam, Malaysia in 2012. A total number of 438 medical students participated in this study, and the response rate was 87.6%. Data were analyzed using SPSS. Comparisons of the mean scores of Dundee Ready Education Environment Measure (DREEM) subscales were calculated. The t-test was used to determine statistically significant differences.

    RESULTS:
    The majority of the study participants were female, Malay, and from year 3 (68.7%, 65.3%, and 55.7%; respectively). Analysis of each of the 50 items of the DREEM inventory showed that 47 items scored ranged between 2.00 and 3.00, and three items scored below 2.00. These were identified as problem areas in this medical school that are required to be critically addressed. The overall score showed that the medical students' perceptions were positive. The students' perception toward educational environment was positive for all five DREEM subscales.

    CONCLUSION:
    The study found that, in general, the perceptions of the participants about the learning environment were positive. Nevertheless, the study also found there is a need for curriculum improvement in this school and identified priority areas for such improvement.

    KEYWORDS:
    DREEM; Malaysia; learning environment; medical education; students’ perceptions
  17. Fulltext Case Series of Genetically Confirmed Index Cases of Familial Hypercholesterolemia in Primary Care
    Kamal A, Kanchau JD, Shahuri NS, Mohamed-Yassin MS, Baharudin N, Abdul Razak S, et al.
    Am J Case Rep, 2023 Apr 27;24:e939489.
    PMID: 37185657 DOI: 10.12659/AJCR.939489
    BACKGROUND In Malaysia, the prevalence of genetically confirmed heterozygous familial hypercholesterolemia (FH) was reported as 1 in 427. Despite this, FH remains largely underdiagnosed and undertreated in primary care. CASE REPORT In this case series, we report 3 FH cases detected in primary care due to mutations in the low-density lipoprotein receptor (LDLR), apolipoprotein-B (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. The mutations in case 1 (frameshift c.660del pathogenic variant in LDLR gene) and case 2 (missense c.10579C>T pathogenic variant in APOB gene) were confirmed as pathogenic, while the mutation in case 3 (missense c.277C>T mutation in PCSK9 gene) may have been benign. In case 1, the patient had the highest LDL-c level, 8.6 mmol/L, and prominent tendon xanthomas. In case 2, the patient had an LDL-c level of 5.7 mmol/L and premature corneal arcus. In case 3, the patient had an LDL-c level of 5.4 mmol/L but had neither of the classical physical findings. Genetic counseling and diagnosis were delivered by primary care physicians. These index cases were initially managed in primary care with statins and therapeutic lifestyle modifications. They were referred to the lipid specialists for up-titration of lipid lowering medications. First-degree relatives were identified and referred for cascade testing. CONCLUSIONS This case series highlights different phenotypical expressions in patients with 3 different FH genetic mutations. Primary care physicians should play a pivotal role in the detection of FH index cases, genetic testing, management, and cascade screening of family members, in partnership with lipid specialists.
  18. Fulltext Reducing Premature Coronary Artery Disease in Malaysia by Early Identification of Familial Hypercholesterolemia Using the Familial Hypercholesterolemia Case Ascertainment Tool (FAMCAT): Protocol for a Mixed Methods Evaluation Study
    Ramli AS, Qureshi N, Abdul-Hamid H, Kamal A, Kanchau JD, Shahuri NS, et al.
    JMIR Res Protoc, 2023 Jun 02;12:e47911.
    PMID: 37137823 DOI: 10.2196/47911
    BACKGROUND: Familial hypercholesterolemia (FH) is predominantly caused by mutations in the 4 FH candidate genes (FHCGs), namely, low-density lipoprotein receptor (LDLR), apolipoprotein B-100 (APOB-100), proprotein convertase subtilisin/kexin type 9 (PCSK9), and the LDL receptor adaptor protein 1 (LDLRAP1). It is characterized by elevated low-density lipoprotein cholesterol (LDL-c) levels leading to premature coronary artery disease. FH can be clinically diagnosed using established clinical criteria, namely, Simon Broome (SB) and Dutch Lipid Clinic Criteria (DLCC), and can be identified using the Familial Hypercholesterolemia Case Ascertainment Tool (FAMCAT), a primary care screening tool.

    OBJECTIVE: This study aims to (1) compare the detection rate of genetically confirmed FH and diagnostic accuracy between the FAMCAT, SB, and DLCC in the Malaysian primary care setting; (2) identify the genetic mutation profiles, including novel variants, in individuals with suspected FH in primary care; (3) explore the experience, concern, and expectation of individuals with suspected FH who have undergone genetic testing in primary care; and (4) evaluate the clinical utility of a web-based FH Identification Tool that includes the FAMCAT, SB, and DLCC in the Malaysian primary care setting.

    METHODS: This is a mixed methods evaluation study conducted in 11 Ministry of Health primary care clinics located at the central administrative region of Malaysia. In Work stream 1, the diagnostic accuracy study design is used to compare the detection rate and diagnostic accuracy of the FAMCAT, SB, and DLCC against molecular diagnosis as the gold standard. In Work stream 2, the targeted next-generation sequencing of the 4 FHCGs is used to identify the genetic mutation profiles among individuals with suspected FH. In Work stream 3a, a qualitative semistructured interview methodology is used to explore the experience, concern, and expectation of individuals with suspected FH who have undergone genetic testing. Lastly, in Work stream 3b, a qualitative real-time observation of primary care physicians using the "think-aloud" methodology is applied to evaluate the clinical utility of a web-based FH Identification Tool.

    RESULTS: The recruitment for Work stream 1, and blood sampling and genetic analysis for Work stream 2 were completed in February 2023. Data collection for Work stream 3 was completed in March 2023. Data analysis for Work streams 1, 2, 3a, and 3b is projected to be completed by June 2023, with the results of this study anticipated to be published by December 2023.

    CONCLUSIONS: This study will provide evidence on which clinical diagnostic criterion is the best to detect FH in the Malaysian primary care setting. The full spectrum of genetic mutations in the FHCGs including novel pathogenic variants will be identified. Patients' perspectives while undergoing genetic testing and the primary care physicians experience in utilizing the web-based tool will be established. These findings will have tremendous impact on the management of patients with FH in primary care and subsequently reduce their risk of premature coronary artery disease.

    INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/47911.

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