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  1. Zaharan NL, Williams D, Bennett K
    Ir J Med Sci, 2014 Jun;183(2):311-8.
    PMID: 24013870 DOI: 10.1007/s11845-013-1011-1
    BACKGROUND: Over the last decade there have been significant changes in the prescribing of antidiabetic therapies. It is of interest to know about these trends and variations in the Irish population so that future prescribing patterns can be estimated.

    AIMS: To examine the trends in prescribed antidiabetic treatments, including variations across age, gender, socioeconomic status and regions in the Irish population over the last 10 years.

    METHODS: The Irish national pharmacy claims database was used to identify patients ≥ 16 years dispensed antidiabetic agents (oral or insulin) from January 2003 to December 2012 through the two main community drug schemes for diabetes. The rate of prescribing per 1,000 population was calculated. Logistic regression was used to examine variations in prescribing in patients with diabetes.

    RESULTS: There was a significant increase in the prescribing of fast and long-acting insulin analogues with a rapid decline in the prescribing of human insulin (p < 0.0001). Increased prescribing of metformin, incretin modulators and fixed oral combination agents was observed (p < 0.0001). Females and older aged patients were more likely to be prescribed human insulin than other insulins. Metformin was less likely while sulphonylureas were more likely to be prescribed in older than younger aged patients. Socioeconomic differences were observed in increased prescribing of the newer and more expensive antidiabetic agents in the non-means tested scheme. Regional variations were observed in the prescribing of both insulin and oral antidiabetic agents.

    CONCLUSION: There has been an increase over time in the prescribing of both insulin and oral antidiabetic agents in the Irish population with increasing uptake of newer antidiabetic agents. This has implications for projecting future uptake and expenditure of these agents given the rising level of diabetes in the population.

  2. Zaharan NL, Williams D, Bennett K
    Br J Clin Pharmacol, 2013 Apr;75(4):1118-24.
    PMID: 22845189 DOI: 10.1111/j.1365-2125.2012.04403.x
    (i) To examine the incidence of new onset treated diabetes in patients treated with different types of statins and (ii) the relationship between the duration and dose of statins and the subsequent development of new onset treated diabetes.
  3. Loh DA, Moy FM, Zaharan NL, Mohamed Z
    PLoS One, 2013;8(12):e82885.
    PMID: 24349385 DOI: 10.1371/journal.pone.0082885
    Escalating weight gain among the Malaysian paediatric population necessitates identifying modifiable behaviours in the obesity pathway.
  4. Loh DA, Moy FM, Zaharan NL, Jalaludin MY, Mohamed Z
    Pediatr Obes, 2017 02;12(1):e1-e5.
    PMID: 26843446 DOI: 10.1111/ijpo.12108
    BACKGROUND: Investigations on sugar-sweetened beverage (SSB) intake and cardiometabolic risks among Asians are scant.

    OBJECTIVES: This study aimed to examine associations between SSB intake and cardiometabolic risks among Malaysian adolescents.

    METHODS: Anthropometric data, blood pressure (BP), fasting blood glucose (FBG), lipid profiles and insulin levels measured involved 873 adolescents (aged 13 years). SSB intake, dietary patterns and physical activity level (PAL) were self-reported.

    RESULTS: Mean SSB consumption was 177.5 mL day-1 with significant differences among ethnicities (Malay, Chinese, Indians and Others) (p 

  5. Loh DA, Moy FM, Zaharan NL, Mohamed Z
    Child Care Health Dev, 2015 Nov;41(6):1216-26.
    PMID: 25873448 DOI: 10.1111/cch.12252
    Physical functioning and psychological resilience in adulthood is shaped during adolescence. Self-reported health-related quality of life (HRQoL) assessments during this life phase are important first-hand accounts of their well-being. This study aimed, firstly, to identify differences in HRQoL according to gender, ethnicity, socio-economic status and weight status; and secondly, to examine associations between weight status and HRQoL among an urban sample of multi-ethnic adolescents in Kuala Lumpur, Malaysia.
  6. Suki SZ, Zuhdi ASM, Yahya 'AA, Zaharan NL
    BMC Geriatr, 2022 01 04;22(1):23.
    PMID: 34983393 DOI: 10.1186/s12877-021-02724-7
    BACKGROUND: Octogenarians and beyond have often been neglected in the populational study of disease despite being at the highest point of non-modifiable disease risk burden and the fastest-growing age group for the past decade. This study examined the characteristics and in-hospital management of octogenarian patients with acute coronary syndrome (ACS) in a multi-ethnic, middle-income country in South East Asia.

    METHOD: This retrospective study utilised the Malaysian National Cardiovascular Disease- ACS (NCVD-ACS) registry. Consecutive patient data of those ≥80 years old admitted with ACS at 24 participating hospitals from 2008 to 2017 (n = 3162) were identified. Demographics, in-hospital intervention, and evidence-based pharmacotherapies over the 10-years were examined and compared across groups of interests using the Chi-square test. Multivariate logistic regression was used to calculate the adjusted odds ratio of receiving individual therapies according to patients' characteristics.

    RESULTS: Octogenarians made up 3.8% of patients with ACS in the NCVD-ACS registry (mean age = 84, SD ± 3.6) from 2008 until 2017. The largest ethnic group was Chinese (44%). Most octogenarians (95%) have multiple cardiovascular risk factors, with hypertension (82%) being the main. Non-ST-elevation myocardial infarction (NSTEMI) predominated (38%, p 

  7. Suki SZ, Zuhdi ASM, Yahya A, Zaharan NL
    J Geriatr Cardiol, 2025 Feb 28;22(2):237-245.
    PMID: 40104834 DOI: 10.26599/1671-5411.2025.02.004
    OBJECTIVES: To examine 5-year trends and variations in dual antiplatelet therapy (DAPT) prescription among multiethnic Malaysian patients aged 60 years and older.

    METHODS: Using the Malaysian National Cardiovascular Disease-Acute Coronary Syndrome (NCVD-ACS) registry, DAPT 5-year temporal trends prescribing patterns at discharge were examined. Multivariate logistic regression was used to calculate the adjusted odds ratio (aOR) of DAPT prescription. The 1-year all-cause mortality by Cox proportional hazard regression model (adjusted hazard ratio, aHR) using inverse proportional weighting covariates adjustment was performed to assess DAPT prognostic impacts.

    RESULTS: Data of patients aged 60 years and older were extracted from 2013 to 2017 (n = 3718, mean age: 68 ± 6.74 years, men: 72%, and Malay ethnicity: 43%). The majority of patients were diagnosed with non-ST-segment elevation acute coronary syndrome (63%), predisposed hypertension (76%) and were overweight (74%), while only 35% of patients underwent percutaneous coronary intervention. Over the five years, there was a significant increasing trend in DAPT prescriptions (P < 0.001), with the aspirin-clopidogrel combination being the most common. Aspirin-ticagrelor prescriptions have also increased over the years. Variations in DAPT prescriptions were observed based on patient characteristics. Patients who underwent percutaneous coronary intervention were more likely to be prescribed DAPT in general (aOR = 2.53, 95% CI: 1.95-3.28, P < 0.001) and aspirin-ticagrelor specifically (aOR = 7.76, 95% CI: 5.65-10.68, P < 0.001). Patients with chronic lung disease (aOR = 0.62, 95% CI: 0.42-0.92, P = 0.02) and a history of angina within two weeks (aOR = 0.69, 95% CI: 0.56-0.85, P < 0.001) were approximately 30% less likely to be prescribed DAPT. Approximately 15% of 1-year all-cause mortality were reported. Older patients prescribed DAPT showed significantly higher survival rates than those who were not (aHR < 1.0, P < 0.001). Aspirin-ticagrelor was associated with higher survival rates than aspirin-clopidogrel (aHR = 0.21, 95% CI: 0.11-0.40, P < 0.001).

    CONCLUSIONS: Despite the optimal prescription rate and variation of DAPT in the older Malaysian population, there is room for investigation and improvement in the prescription of newer DAPT combinations that have been suggested to improve patient survival.

  8. Wan Md Adnan WA, Zaharan NL, Wong MH, Lim SK
    PLoS One, 2014;9(12):e114262.
    PMID: 25546434 DOI: 10.1371/journal.pone.0114262
    Chronic kidney disease is an emerging problem in the majority Muslim countries. Despite the uncertainties of the risks involved, some Muslim patients undergoing chronic haemodialysis choose to observe intermittent fasting during the month of Ramadan. This study aims to investigate the effect of Ramadan fasting in haemodialysis patients residing in a tropical climate country.
  9. Mac Guad R, Zaharan NL, Chik Z, Mohamed Z, Peng NK, Adnan WA
    Transplant Proc, 2016 Jan-Feb;48(1):81-7.
    PMID: 26915847 DOI: 10.1016/j.transproceed.2016.01.001
    BACKGROUND: The aim of this study was to compare the within-patient variability trough levels (Co), dose-adjusted Co, and dose requirements of Prograf and Advograf with CYP3A5 polymorphisms in Malaysia renal transplant recipients.
    METHODS: Stable post-renal transplantation patients switched from Prograf to Advograf were retrospectively identified from University Malaya Medical Centre (n = 28). Co and concomitant tacrolimus dose 6 months preconversion and postconversion were examined. CYP3A5 was genotyped using reverse transcriptase polymerase chain reaction. Wilcoxon signed rank test and Mann-Whitney U test were used to compare Co and dose between formulations and according to genotypes.
    RESULTS: There was a significant difference in the whole-blood tacrolimus Co between the 2 groups (6.16 ± 1.74 ng/mL vs 4.90 ± 1.06 ng/mL; P = .0001). The mean daily maintenance dose of Prograf was 3.9 ± 2.0 mg/kg (0.06 mg/kg/d), which was reduced to 3.3 ± 1.7 mg/d (0.04 mg/kg/d) with Advograf (P = .01). The mean maintenance dose of tacrolimus required for those with CYP3A5*1/*1 (high-expressive) was significantly higher than those with CYP3A5*1/*3 (intermediate-expressive) and CYP3A5*3/*3 (low-expressive) (P < .01) for both formulations. Comparing those with CYP3A5*1/*1, the average dose-adjusted Co was significantly higher in patients with CYP3A5*3/*3 with Advograf (P < .05).
    CONCLUSIONS: The requirement for daily maintenance dose was higher in those with CYP3A5*1/*1 variants in both tacrolimus formulations in the Malaysian patients. Furthermore, those with CYP3A5*3/*3 demonstrated significantly higher dose-adjusted Co with Advograf.
  10. Zain SM, Mohamed Z, Jalaludin MY, Fauzi F, Hamidi A, Zaharan NL
    Pharmacogenet Genomics, 2015 Oct;25(10):501-10.
    PMID: 26240981 DOI: 10.1097/FPC.0000000000000164
    Orexigenic actions mediated by neuropeptide-Y (NPY) promote body weight regulation. Genetic variations in the NPY gene could therefore influence susceptibility to obesity, but results have been conflicting. We have carried out, for the first time, a case-control study to examine the effect of NPY rs16147 and rs5574 variants with the risk of obesity in Asians and also a meta-analysis to summarize the effect of these variants including that of the widely studied rs16139.
  11. Zaharan NL, Muhamad NH, Jalaludin MY, Su TT, Mohamed Z, Mohamed MNA, et al.
    PMID: 29755414 DOI: 10.3389/fendo.2018.00209
    Background: Several non-synonymous single-nucleotide polymorphisms (nsSNPs) have been shown to be associated with obesity. Little is known about their associations and interactions with physical activity (PA) in relation to adiposity parameters among adolescents in Malaysia.

    Methods: We examined whether (a) PA and (b) selected nsSNPs are associated with adiposity parameters and whether PA interacts with these nsSNPs on these outcomes in adolescents from the Malaysian Health and Adolescents Longitudinal Research Team study (n = 1,151). Body mass indices, waist-hip ratio, and percentage body fat (% BF) were obtained. PA was assessed using Physical Activity Questionnaire for Older Children (PAQ-C). Five nsSNPs were included: beta-3 adrenergic receptor (ADRB3) rs4994, FABP2 rs1799883, GHRL rs696217, MC3R rs3827103, and vitamin D receptor rs2228570, individually and as combined genetic risk score (GRS). Associations and interactions between nsSNPs and PAQ-C scores were examined using generalized linear model.

    Results: PAQ-C scores were associated with % BF (β = -0.44 [95% confidence interval -0.72, -0.16], p = 0.002). The CC genotype of ADRB3 rs4994 (β = -0.16 [-0.28, -0.05], corrected p = 0.01) and AA genotype of MC3R rs3827103 (β = -0.06 [-0.12, -0.00], p = 0.02) were significantly associated with % BF compared to TT and GG genotypes, respectively. Significant interactions with PA were found between ADRB3 rs4994 (β = -0.05 [-0.10, -0.01], p = 0.02) and combined GRS (β = -0.03 [-0.04, -0.01], p = 0.01) for % BF.

    Conclusion: Higher PA score was associated with reduced % BF in Malaysian adolescents. Of the nsSNPs, ADRB3 rs4994 and MC3R rs3827103 were associated with % BF. Significant interactions with PA were found for ADRB3 rs4994 and combined GRS on % BF but not on measurements of weight or circumferences. Targeting body fat represent prospects for molecular studies and lifestyle intervention in this population.

  12. Ling JC, Mohamed MN, Jalaludin MY, Rampal S, Zaharan NL, Mohamed Z
    Sci Rep, 2016 11 08;6:36270.
    PMID: 27824069 DOI: 10.1038/srep36270
    Hyperinsulinaemia is the earliest subclinical metabolic abnormality, which precedes insulin resistance in obese children. An investigation was conducted on the potential predictors of fasting insulin and insulin resistance among overweight/obese adolescents in a developing Asian country. A total of 173 overweight/obese (BMI > 85th percentile) multi-ethnic Malaysian adolescents aged 13 were recruited from 23 randomly selected schools in this cross-sectional study. Waist circumference (WC), body fat percentage (BF%), physical fitness score (PFS), fasting glucose and fasting insulin were measured. Insulin resistance was calculated using homeostasis model assessment of insulin resistance (HOMA-IR). Adjusted stepwise multiple regression analysis was performed to predict fasting insulin and HOMA-IR. Covariates included pubertal stage, socioeconomic status, nutritional and physical activity scores. One-third of our adolescents were insulin resistant, with girls having significantly higher fasting insulin and HOMA-IR than boys. Gender, pubertal stage, BMI, WC and BF% had significant, positive moderate correlations with fasting insulin and HOMA-IR while PFS was inversely correlated (p 
  13. Rahmadhani R, Zaharan NL, Mohamed Z, Moy FM, Jalaludin MY
    PLoS One, 2017;12(6):e0178695.
    PMID: 28617856 DOI: 10.1371/journal.pone.0178695
    BACKGROUND: The vitamin D receptor (VDR) gene is expressed abundantly in different tissues; including adipocytes and pancreatic beta cells. The rs1544410 or BsmI single nucleotide polymorphism (SNP) in the intronic region of the VDR gene has been previously associated with vitamin D levels, obesity and insulin resistance.

    AIMS: This study was aimed to examine the association between BsmI polymorphism and risk of vitamin D deficiency, obesity and insulin resistance in adolescents living in a tropical country.

    METHODS: Thirteen-year-old adolescents were recruited via multistage sampling from twenty-three randomly selected schools across the city of Kuala Lumpur, Malaysia (n = 941). Anthropometric measurements were obtained. Obesity was defined as body mass index higher than the 95th percentile of the WHO chart. Levels of fasting serum vitamin D (25-hydroxyvitamin D (25(OH)D)), glucose and insulin were measured. HOMA-IR was calculated as an indicator for insulin resistance. Genotyping was performed using the Sequenom MassARRAY platform (n = 807). The associations between BsmI and vitamin D, anthropometric parameters and HOMA-IR were examined using analysis of covariance and logistic regression.

    RESULT: Those with AA genotype of BsmI had significantly lower levels of 25(OH)D (p = 0.001) compared to other genotypes. No significant differences was found across genotypes for obesity parameters. The AA genotype was associated with higher risk of vitamin D deficiency (p = 0.03) and insulin resistance (p = 0.03) compared to GG. The A allele was significantly associated with increased risk of vitamin D deficiency compared to G allele (adjusted odds ratio (OR) = 1.63 (95% Confidence Interval (CI) 1.03-2.59, p = 0.04). In those with concurrent vitamin D deficiency, having an A allele significantly increased their risk of having insulin resistance compared to G allele (adjusted OR = 2.66 (95% CI 1.36-5.19, p = 0.004).

    CONCLUSION: VDR BsmI polymorphism was significantly associated with vitamin D deficiency and insulin resistance, but not with obesity in this population.

  14. Venkatason P, Zaharan NL, Ismail MD, Wan Ahmad WA, Mahmood Zuhdi AS
    Eur J Clin Pharmacol, 2018 Jul;74(7):953-960.
    PMID: 29582106 DOI: 10.1007/s00228-018-2451-3
    PURPOSE: Information is lacking on prescribing of preventative cardiovascular pharmacotherapies for patients with non-ST elevation myocardial infarction (NSTEMI) in the Asian region. This study examined the prescribing rate of these pharmacotherapies, comparing NSTEMI to STEMI, and variations across demographics and clinical factors within the NSTEMI group in the multi-ethnic Malaysian population.

    METHODS: This is a retrospective analysis of the Malaysian National Cardiovascular Disease Database-Acute Coronary Syndrome registry from year 2006 to 2013 (n = 30,873). On-discharge pharmacotherapies examined were aspirin, ADP-antagonists, statins, ACE-inhibitors, angiotensin-II-receptor blockers, and beta-blockers. Multivariate logistic regression was used to calculate adjusted odds ratio of receiving individual pharmacotherapies according to patients' characteristics in NSTEMI patients (n = 11,390).

    RESULTS: Prescribing rates for cardiovascular pharmacotherapies had significantly increased especially for ADP-antagonists (76%) in NSTEMI patients. More than 85% were prescribed statins and antiplatelets but rates remained significantly lower compared to STEMI. Women and those over 65 years old were less likely to be prescribed these pharmacotherapies compared to men and younger NSTEMI patients. Chinese and Indians were more likely to receive selected pharmacotherapies compared to Malays (main ethnicity). Geographical variations were observed; East Malaysian (Malaysian Borneo) patients were less likely to receive these compared to Western region of Malaysian Peninsular. Underprescribing in patients with risk factors such as diabetes were observed with other co-morbidities influencing prescribing selectively.

    CONCLUSION: This study uncovers demographic and clinical variations in cardiovascular pharmacotherapies prescribing for NSTEMI. Concerted efforts by policy makers, specialty societies, and physicians are required focusing on elderly, women, Malays, East Malaysians, and high-risk patients.

  15. Guad RM, Taylor-Robinson AW, Wu YS, Gan SH, Zaharan NL, Basu RC, et al.
    BMC Nephrol, 2020 09 07;21(1):388.
    PMID: 32894076 DOI: 10.1186/s12882-020-02052-9
    BACKGROUND: New-onset diabetes after transplantation (NODAT) is associated with reduced patient and graft survival. This study examined the clinical and selected genetic factors associated with NODAT among renal-transplanted Malaysian patients.

    METHODS: This study included 168 non-diabetic patients (58% males, 69% of Chinese ethnicity) who received renal transplantation between 1st January 1994 to 31st December 2014, and were followed up in two major renal transplant centres in Malaysia. Fasting blood glucose levels were used to diagnose NODAT in patients who received renal transplantation within 1 year. Two single nucleotide polymorphisms (SNPs), namely; rs1494558 (interleukin-7 receptor, IL-7R) and rs2232365 (mannose-binding leptin-2, MBL2) were selected and genotyped using Sequenom MassArray platform. Cox proportional hazard regression analyses were used to examine the risk of developing NODAT according to the different demographics and clinical covariates, utilizing four time-points (one-month, three-months, six-months, one-year) post-transplant.

    RESULTS: Seventeen per cent of patients (n = 29, 55% males, 69% Chinese) were found to have developed NODAT within one-year of renal transplantation based on their fasting blood glucose levels. NODAT patients had renal transplantation at an older age compared to non-NODAT (39.3 ± 13.4 vs 33.9 ± 11.8 years, p = 0.03). In multivariate analysis, renal-transplanted patients who received a higher daily dose of cyclosporine (mg) were associated with increased risk of NODAT (Hazard ratio (HR) =1.01 per mg increase in dose, 95% confidence interval (CI) 1.00-1.01, p = 0.002). Other demographic (gender, ethnicities, age at transplant) and clinical factors (primary kidney disease, type of donor, place of transplant, type of calcineurin inhibitors, duration of dialysis pre-transplant, BMI, creatinine levels, and daily doses of tacrolimus and prednisolone) were not found to be significantly associated with risk of NODAT. GA genotype of rs1494558 (HR = 3.15 95% CI 1.26, 7.86) and AG genotype of rs2232365 (HR = 2.57 95% CI 1.07, 6.18) were associated with increased risk of NODAT as compared to AA genotypes.

    CONCLUSION: The daily dose of cyclosporine and SNPs of IL-7R (rs1494558) and MBL2 (rs2232365) genes are significantly associated with the development of NODAT in the Malaysian renal transplant population.

  16. Venkatason P, Zubairi YZ, Zaharan NL, Wan Ahmad WA, Hafidz MI, Ismail MD, et al.
    BMJ Open, 2019 11 19;9(11):e030159.
    PMID: 31748289 DOI: 10.1136/bmjopen-2019-030159
    OBJECTIVE: Young women form a minority but an important group of patients with acute myocardial infarction (MI) as it can potentially cause devastating physical and socioeconomic impact. This study was aimed to investigate the characteristics and outcomes of young women with MI in Malaysia.

    DESIGN: This is a retrospective analysis of women with ST-elevation MI (STEMI) and non-STEMI (NSTEMI) from 18 hospitals across Malaysia using the Malaysian National Cardiovascular Database registry-acute coronary syndrome (NCVD-ACS).

    PARTICIPANTS: Women patients diagnosed with acute MI from year 2006 to 2013 were identified and divided into young (age ≤ 45, n=292) and older women (age >45, n=5580).

    PRIMARY OUTCOME MEASURE: Comparison of demographics, clinical characteristics and in-hospital management was performed between young and older women. In-hospital and 30-day all-cause mortality were examined.

    RESULTS: Young women (mean age 39±4.68) made up 5% of women with MI and were predominantly of Malay ethnicities (53.8%). They have a higher tendency to present as STEMI compared with older women. Young women have significantly higher rates of family history of premature coronary artery disease (CAD) (20.5% vs 7.8% p<0.0001). The prevalence of risk factors, such as hypertension, diabetes and dyslipidaemia was high in both groups. The primary reperfusion strategy was thrombolysis with no significant differences observed in the choice of intervention for both groups. Other than aspirin, rates of prescriptions for evidence-based medications were similar with >80% prescribed statins and aspirin. The all-cause mortality rates of young women were lower for both in-hospital and 30 days, especially in those with STEMI with adjusted mortality ratio to the older group, was 1:9.84.

    CONCLUSION: Young women with MI were over-represented by Malays and those with a family history of premature CAD. Preventive measures are needed to reduce cardiovascular risks in young women. Although in-hospital management was similar, short-term mortality outcomes favoured young compared with older women.

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