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  1. Diong SC, Syed Zakaria SZ, Rasat R, Wan Ismail WJ
    Med J Malaysia, 2019 08;74(4):288-295.
    PMID: 31424035
    INTRODUCTION: Parental knowledge on nephrotic syndrome and disease relapse is important for early recognition and treatment of relapse to prevent the complications. Parental knowledge on nephrotic syndrome was reported to be inadequate from published studies. To date, there is no study on parental knowledge on childhood nephrotic syndrome in Malaysia. This study is thus aimed at to determine the level of knowledge on NS and disease relapse among parents of children with nephrotic syndrome and determine factors that influence knowledge on nephrotic syndrome and disease relapse.

    STUDY DESIGN AND METHODS: This was a cross-sectional study conducted in Paediatric Nephrology Clinic, Hospital Selayang from November 2016 to November 2017. Seventy-eight parents were recruited based on universal sampling. Selfadministered questionnaire in Bahasa Malaysia and English was designed through focus group discussion with five subject matter experts and validated through content validity. Data was analysed using IBM SPSS Statistics 23.0.

    RESULTS: Majority of parents or guardians (91%) were able to answer more than 50% of the questions correctly. Of these, 56% were able to answer more than 75% of the questions correctly. A 'cut-off' of 75% was defined as good knowledge. Parents of children with frequent relapses had higher parental knowledge and this was statistically significant (p=0.025).

    CONCLUSION: Parental knowledge on nephrotic syndrome and disease relapse was still inadequate as only 56% parents had good knowledge. The main areas of deficit in parental knowledge were related to medications, infections, home urine dipstick monitoring, and recognition of warning signs during relapse.

  2. Koo HW, Ismail J, Yang WW, Syed Zakaria SZ
    Front Pediatr, 2020;8:608242.
    PMID: 33537265 DOI: 10.3389/fped.2020.608242
    Introduction: Children with autism spectrum disorder (ASD) have a variety of co-morbid medical problems, including sleep disturbances. Prevalence of sleep disorders has been reported to be higher in this group as compared to the general population. Identifying sleep problems in children with ASD may help increase awareness and improve the overall quality of care for them. The aim of this study was to determine the prevalence of sleep problems and associated factors in a group of Malaysian children aged 6-16 years, with ASD. Method: This is a cross-sectional study at the Child Development Centre of UKM Medical Centre (UKM MC) on ASD children aged 6-16 years. Demographic data was obtained and the Sleep Disturbances Scale for Children (SDSC) questionnaire was completed by the main caregiver. Logistic regression analysis was used to determine factors related to higher total SDSC scores. Results: A total of 128 patients were recruited (111 boys) with a median age of 8 years 3 months (IQR: 2 years 10 months). Forty-seven (36.7%) of them obtained total SDSC scores in the pathological range with 19 (14.8%) scoring high for overall disturbances and 28 (21.9%) for at least one subtype of sleep disorders: 25 (19.5%) DIMS, 18 (14.1%) SBD, 10 (7.8%) DOES, 5 (3.9%) DOA, 6 (4.7%) SWTD, and 3 (2.3%) SHY. More than half of the children (57.8%) were reported to have sufficient sleep duration of 8-11 h, but longer sleep latency of at least 15 min (82.8%). Half of the ASD children also had co-morbidities in which one-third (34.4%) had attention-deficit hyperactivity disorder (ADHD). Using logistic regression analysis, four factors were significantly associated with higher total SDSC scores; female gender (p = 0.016), older age group (11-16 years old) (p = 0.039), shorter sleep length (p = 0.043), and longer sleep latency (p < 0.001). Conclusion: The prevalence of sleep disturbances is high among Malaysian children with ASD, especially DIMS. Female gender, older age group, shorter sleep length, and longer sleep latency were found to be associated with the sleep disturbances. Evaluation of sleep problems should form part of the comprehensive care of children with ASD.
  3. Mohamed Fuad Z, Mahadzir H, Syed Zakaria SZ, Mohamed Ibrahim N
    Front Public Health, 2020;8:577940.
    PMID: 33282811 DOI: 10.3389/fpubh.2020.577940
    Background: Stroke is highly prevalent globally and is an important cause of cognitive impairment and dementia. Aims: We determined the frequency of post-stroke cognitive impairment (PSCI) at 1, 3, and 6 months among patients with first clinical ischemic stroke compared to risk and age-matched controls. Methods: This study involved 32 cases and 32 controls, and was conducted over 6 months. Cases were inpatients aged >60 with first clinical ischemic stroke. Controls were age-matched subjects without prior stroke. Montreal Cognitive Assessment (MoCA) was performed in all patients at 1, 3, and 6 month post stroke. A MoCA score of <26 was used for mild PSCI and <22 for moderate PSCI (post stroke dementia). Results: Post-stroke dementia was detected in 12 patients (37.5%) at 1st month, in 13 (40.6%) at 3rd month and 15 (48.4%) at 6th months. Mild PSCI was present in 7 patients (21.6%) at 1 month, 16 patients (50%) at 3 months, and 15 patients (48%) at 6 months. The odds ratio (OR) for post-stroke dementia was 3.2 (95%CI 0.98-10.68; p = 0.05) at 1 month; 3.69(95% CI 1.13-12.11; p = 0.031) at 3 months, and 4.88 (95% CI 1.49-15.99; p = 0.009) at 6 months. Years of education was an independent predictor for dementia (OR 0.60; p = 0.046). The OR for post-stroke dementia at 6th month was 7.23 with education level adjusted (95%CI 1.46-35.86, p = 0.015). Conclusion: The frequency of PSCI was high as early as 1 month after stroke. Stroke alone conferred a 7.2 times risk for post-stroke dementia compared to controls.
  4. Othman H, Abu Yamin AH, Md Isa N, Bahadzor B, Syed Zakaria SZ
    Malays J Pathol, 2020 Aug;42(2):209-214.
    PMID: 32860373
    INTRODUCTION: Prostate health index (PHI) has been shown to have better diagnostic accuracy in predicting prostate cancer (PCa) in men with total prostate-specific antigen (PSA) levels between 4-10ng/ml. However, little is known of its value in men with elevated PSA beyond this range. This study aimed to evaluate the diagnostic performance of PHI in Malaysian men with elevated PSA values ≤ 20ng/ml.

    MATERIALS AND METHODS: From March 2015 to August 2016, all men consecutively undergoing transrectal ultrasound (TRUS)-guided prostate biopsy with total PSA values ≤ 20ng/ ml were recruited. Blood samples were taken immediately before undergoing prostate biopsy. The performance of total PSA, %fPSA, %p2PSA and PHI in determining the presence of PCa on prostate biopsy were compared.

    RESULTS: PCa was diagnosed in 25 of 84 patients (29.7%). %p2PSA and PHI values were significantly higher (p<0.05) in patients with PCa than those without PCa. The areas under the receiver operating characteristic curves for total PSA, %fPSA, %p2PSA and PHI were 0.558, 0.560, 0.734 and 0.746, respectively. At 90% sensitivity, the specificity of PHI (42.4%) was five times better than total PSA (8.5%) and two times better than %fPSA (20.3%). By utilising PHI cut-off >22.52, 27 of 84 (32.1%) patients could have avoided undergoing biopsy.

    CONCLUSION: Findings of our study support the potential clinical effectiveness of PHI in predicting PCa in a wider concentration range of total PSA up to 20ng/ml.

  5. Shafie H, Syed Zakaria SZ, Adli A, Shareena I, Rohana J
    Pediatr Int, 2017 Jul;59(7):776-780.
    PMID: 28370991 DOI: 10.1111/ped.13285
    BACKGROUND: Occlusive body wrap using polyethylene plastic applied immediately after birth had been shown to reduce hypothermia among preterm infants. Various adjunct methods have been studied in an attempt to further reduce the incidence of hypothermia. This study was conducted to determine whether polyethylene cap is more effective than cotton cap as an adjunct to polyethylene occlusive body wrap in reducing hypothermia in preterm infants.

    METHODS: The subjects consisted of preterm infants 24-34 weeks' gestation born at Universiti Kebangsaan Malaysia Medical Centre. Infants were randomly assigned to NeoCap or control groups. Infants in both groups were wrapped in polyethylene sheets from the neck downwards immediately after birth without prior drying. Infants in the control group had their heads dried and subsequently covered with cotton caps while infants in the NeoCap group had polyethylene caps put on without drying. Axillary temperature was measured on admission to the neonatal intensive care unit (NICU), and after having been stabilized in the incubator.

    RESULTS: Among the 80 infants recruited, admission hypothermia (axillary temperature <36.5°C) was present in 37 (92.5%) and in 40 (100%) in the NeoCap and control groups, respectively. There was no significant difference in mean temperature on NICU admission between the two groups (35.3 vs 35.1°C, P = 0.36). Mean post-stabilization temperature, however, was significantly higher in the NeoCap group (36.0 vs 35.5°C, P = 0.01).

    CONCLUSION: Combined use of polyethylene body wrap and polyethylene cap was associated with a significantly higher mean post-stabilization temperature compared with polyethylene body wrap and cotton cap.

  6. M Selveindran N, Syed Zakaria SZ, Jalaludin MY, Rasat R
    Horm Res Paediatr, 2017;88(5):324-330.
    PMID: 28965114 DOI: 10.1159/000478780
    BACKGROUND/AIMS: Disorders of sex development (DSD) are a heterogeneous group of rare conditions. Evidence-based treatment is challenged by a lack of clinical longitudinal outcome studies. We sought to investigate the quality of life of children with DSD other than congenital adrenal hyperplasia.

    METHODS: The participants (aged 6-18 years) were 23 patients raised as males and 7 patients raised as females. Control data were obtained from representatives of the patients' siblings matched for age and gender. The Pediatric Quality of Life InventoryTM Version 4.0 (PedsQL) Generic Core Scales were used as the study tool.

    RESULTS: In comparison with the reference data, the patient group had significantly lower overall PedsQL (p < 0.01) and school functioning (p < 0.01) scores. Also, the total PedsQL score was significantly lower in patients with DSD who were of female social sex as compared to the controls who were females. Family income, surgical procedures, degree of virilization, and mode of puberty did not influence the PedsQL scores.

    CONCLUSION: This study revealed a poorer quality of life for patients with DSD as compared to the age-matched control group. This highlights the need for a skilled multidisciplinary team to manage this group of patients.

  7. Idris AN, Chandran V, Syed Zakaria SZ, Rasat R
    Int J Endocrinol, 2014;2014:483718.
    PMID: 24799898 DOI: 10.1155/2014/483718
    The aim of this study was to determine the behavioral outcome in children with CAH and to identify the risk factors that may influence it. Participants (aged 6-18 years) included 29 girls and 20 boys with CAH and unaffected siblings (25 girls and 17 boys). Psychological adjustment was assessed with parent reports on the Child Behavior Checklist (CBCL). Information about disease characteristics was obtained from medical records. Our study reveals that there was higher incidence of parent-reported problem of anxious/depressed and withdrawn/depressed behaviours, somatic complaints, social, thought, and attention problems, and rule-breaking, aggressive, internalizing, and externalizing behaviour among children with CAH compared to controls. The prevalence of internalizing behaviour problems was higher in CAH boys compared with that of controls. Psychosocial adjustment of girls with CAH was found to be similar to unaffected female controls and was within the normal population range. Family income may be associated with behavioral outcome. Glucocorticoid dose may reflect disease severity which may be associated with behavioral outcome. We conclude that internalizing behavioral problem was prevalent among boys with CAH reflecting maladaptive adjustment in coping with chronic illness. This highlighted the importance of psychological and social support for the patients and their families.
  8. M Selveindran N, Syed Zakaria SZ, Jalaludin MY, Rasat R
    Int J Endocrinol, 2017;2017:5987490.
    PMID: 28717365 DOI: 10.1155/2017/5987490
    The aim of this study is to determine the behavioural problems of children with 46XY disorders of sex development (DSD) with genital ambiguity and to identify the risk factors that may influence behaviour. The 27 participants (aged 6-18 years) consisted of 21 patients raised as boys and 6 patients raised as girls. Control data were obtained from a representative sibling of each patient who was matched for age and gender. The study tool used was the Child Behaviour Checklist (CBCL), which is a parent-administered questionnaire. The analysis of the behavioural scores revealed that the patient group had poorer scores in the total, externalizing, and internalizing realms. This group also had poorer scores in the anxious-depressed, social, and rule-breaking realms as compared to the control group. In addition, the XY-F group had higher scores (more pathological) than the XY-M group, although the difference in the scores was not statistically significant. A comparison of the prevalence of patients with scores in the clinical range with that of the control group was not statistically significant. These findings support the current recommendations that psychological counselling should be an integral part of the professional support offered to patients with DSD.
  9. Muhammad Azami NA, Salleh SA, Neoh HM, Syed Zakaria SZ, Jamal R
    BMC Res Notes, 2011;4:216.
    PMID: 21714858 DOI: 10.1186/1756-0500-4-216
    BACKGROUND:
    Dengue infection has been an important and serious public health concern in Malaysia ever since its first reported case here in 1902. Nevertheless, to our knowledge, no nationwide investigation has been carried out to determine the actual magnitude of dengue endemicity in the Malaysian population. In this study, we describe a cross sectional seroepidemiology study of dengue IgG seroprevalence in the Malaysian adult population.

    FINDINGS:
    From 1000 subjects (35-74 years old), 91.6% subjects were found to be dengue seropositive. Age is found to be a significant risk factor associated with dengue seroposivity, where the seroprevalence increased with every 10 year increase in age. Nevertheless, gender and ethnicity did not have an effect. Interestingly, there were similar seroprevalence rates between urban and rural samples, showing that dengue is presently not confined to urban areas in Malaysia.

    CONCLUSIONS:
    High dengue IgG seropositivity found in the population is an indication that dengue might be endemic in Malaysia for a long time into the future. Public awareness, proper vector control and vigilant surveillance are critical to keep the infection rates low and to prevent outbreaks.
  10. Latiff ZA, Kamal NA, Jahendran J, Alias H, Goh BS, Syed Zakaria SZ, et al.
    J Pediatr Hematol Oncol, 2010 Jul;32(5):407-10.
    PMID: 20505534 DOI: 10.1097/MPH.0b013e3181e01584
    Vincristine-induced vocal cord paralysis is a rare but serious complication. We report 2 patients with acute lymphoblastic leukemia who developed progressive stridor during induction chemotherapy. There were no clinical features of peripheral or autonomic neuropathy. Flexible laryngoscopy confirmed the diagnosis of bilateral vocal cord palsy; interestingly, the nerve conduction test revealed axonal motor neuropathy involving the median and common peroneal nerves in both patients. The first patient required prolonged ventilatory support necessitating unilateral cordectomy before extubation, whereas the second only required supplemental oxygen therapy. There was resolution of stridor in the first patient after cordectomy and gradual clinical improvement in the second. These cases illustrate that a high index of suspicion of vincristine-induced vocal cord palsy with prompt otolaryngology consultation for laryngoscopy is required in the diagnostic evaluation of a patient who has received vincristine.
  11. Shamsuddin N, Poh BK, Syed Zakaria SZ, Noor MI, Jamal R
    Int J Public Health Res, 2015;5(2):643-653.
    MyJurnal
    Introduction: Validation of instruments is essential when assessing physical activity (PA). The aim of this study was to validate a Malay language version of the International Physical Activity Questionnaire (IPAQ-M) against Actical accelerometer and to determine its reliability and validity.
    Methods: A total of 90 Malay adults aged 35-65 years old participating in The Malaysian Cohort project were recruited for this study. The IPAQ-M is comprised of 12 items, covering vigorous, moderate, walking, sitting and sleeping activities, and was administered on two occasions (Day 1 and Day 9) by interviewing the participants. Participants wore the Actical accelerometer for seven consecutive days between the two interview sessions. Results Validity tests showed that time spent in moderate-vigorous physical activity (MVPA) (min/wk) from IPAQ-M was significantly correlated with MVPA from accelerometer (rho=0.32, p<0.01). Time spent in vigorous activity (rho=0.44) and total activity (rho=0.36) from IPAQ-M were significantly correlated (p<0.01) with that measured by accelerometer, but no correlation was observed for sedentary behaviour. Reliability tests revealed significant correlations between the two interview sessions for all intensities of PA (rho=0.55 to 0.71, p<0.01). Bland-Altman plots showed that time spent in MVPA for IPAQ-M was significantly different from that measured by accelerometer (mean difference: 98.02 min/wk; 95% limits of agreement: -785.33 to 1317.83 min/wk; p<0.01). When classifying people into meeting PA recommendation, the agreement between the two instruments was fair (κ=0.22).
    Conclusions The IPAQ-M has acceptable validity for MVPA, vigorous and total physical activity, and was reliable for assessing the physical activity of Malay adults.
    Keywords Health care workers - Knowledge - Practice - Universal precaution - Health center.
    Study name: The Malaysian Cohort (TMC) Project
  12. Subramaniam SR, Khoo CS, Raymond AA, Che Din N, Syed Zakaria SZ, Tan HJ
    J Clin Neurosci, 2020 Mar;73:31-36.
    PMID: 32094071 DOI: 10.1016/j.jocn.2020.02.003
    The objective of this study is to determine prevalence and factors leading to verbal learning and memory dysfunction among patients with epilepsy. A total of 211 subjects were recruited. Their verbal memory was assessed by Rey's Auditory Verbal Learning Test (RAVLT). This test was further subdivided into four major spheres for analysis, namely the verbal learning, interference list, immediate memory and delayed memory. All data collected were analyzed using Statistical Package for Social Sciences. Among the 211 patients, 55% (n = 116) had focal seizures and the remaining 45% (n = 95) had generalized seizures. Prevalence of verbal learning and memory impairment was high at 39.97% overall, and found most commonly in patients with focal impaired awareness seizures. Verbal learning and immediate memory dysfunction were significantly lower in focal impaired awareness group compared to others. Age more than 50 years, exposure to three or more antiepileptic drugs and use of carbamazepine more than 1000 mg a day were the predictors in poor verbal memory outcome. No statistical difference was observed in the mean RAVLT scores among the gender and hand dominance groups. Between patients with and without electroencephalogram changes as well as brain magnetic resonance imaging changes, the mean RAVLT scores showed no statistically significant difference. Verbal learning and memory impairment is prevalent among the epilepsy patients. The consequences of the memory impairment can be as debilitating as the seizure control. RAVLT is a reliable and practical test in the clinical setting.
  13. Yong SL, Ng BK, Mohd Yassin MAJ, Syed Zakaria SZ, Mohamed Ismail NA
    J Obstet Gynaecol, 2018 May;38(4):461-465.
    PMID: 29390907 DOI: 10.1080/01443615.2017.1372397
    This study was to assess the relationship between late pregnancy haemoglobin A1C (HbA1C) at 29-30 weeks of gestation and adverse pregnancy outcomes (APOs) in 272 pregnant women with pre-existing diabetes. HbA1C ≥6.1% was associated with significantly increased risk of preterm delivery, Caesarean section, large for gestational age (LGA), neonatal respiratory distress, neonatal hypoglycaemia, and composite adverse neonatal outcome (p  5.6% (p = .039). Reduction of HbA1C cut-off from 6.1% to 5.6% improved the sensitivity but reduced the specificity for prediction of APOs. Overall, the receiver operating characteristic (ROC) curves demonstrated the moderate predictive value of late pregnancy HbA1C for APOs. In conclusion, elevated late pregnancy HbA1C levels at 29-30 gestational weeks had a negative impact on APOs in pregnant women with pre-existing diabetes. However, HbA1C cut-off levels of neither ≥6.1% nor >5.6% were ideal for predicting APOs. Impact statement What is already known on this subject: Poorly controlled diabetes is associated with adverse pregnancy outcomes (APOs). Periconceptual haemoglobin A1C (HbA1C) correlates well with the risk of foetal anomaly but is not predictive of APOs at time of delivery. New evidence suggested that late pregnancy HbA1C is predictive of APOs but the definitions of a late pregnancy gestational week and target HbA1C cutpoint remain in doubt. What the results of this study add: This study investigated the relationship between late pregnancy HbA1C levels at 29-30 weeks of gestation and the APOs among pregnant women with pre-existing diabetes. Late pregnancy HbA1C ≥ 6.1% correlated with the risk of APOs but the increased risk of pre-eclampsia only became significant at the lower cut-off of >5.6%. Reducing HbA1C cut-off from 6.1% to 5.6% improved the sensitivity but reduced the specificity for prediction of APOs. Overall, late pregnancy HbA1C had a moderate predictive value for APOs. What the implications are of these findings for clinical practice and/or further research: HbA1C cut-off levels of neither ≥6.1% nor >5.6% were ideal in predicting APOs among pregnant women with pre-existing diabetes. As HbA1C levels tend to drop in pregnancy, caution should be taken when interpreting HbA1C in pregnancy. More multi-centred studies are required to explore the respective glycaemic target for each APO and to determine the ideal timing for late pregnancy HbA1C measurement.
  14. Mohamed M, Lau DSC, Loh CK, Syed Zakaria SZ, Alias H, A Jamal AR, et al.
    MyJurnal
    Introduction: Parents of children with chronic illness such as thalassaemia, experience parental anxiety as a result of multiple stressors; these parents will consequently undergo the process of coping and adjustment in order to overcome the situation. Identifying families who may require psychosocial intervention is an important step towards providing holistic management for these children.

    Methodology: A cross-sectional study was conducted to determine the level of parenting stress amongst parents of children with thalassaemia. Risk factors associated with high parenting stress score were identified. Research instruments used were the Parenting Stress Index/Short Form and Coping Inventory for Stressful Situations.

    Results: A total of 54 subjects were recruited. High total parenting stress score (TPSS, defined at 75th centile) for this cohort was 99.5 whereas the mean TPSS was 86.18. Overall, 24% of these parents have high TPSS. Chinese ethnicity, number of children, monthly income, task-oriented and emotion-oriented coping mechanisms were significantly associated with a high TPSS. Logistic regression analysis revealed that low task-oriented but high emotion-oriented scores were risk factors with the greatest predictive power.

    Conclusion: Early recognition of parenting stress is important to identify at risk parents so that interventions such as counseling and social support may be given.
  15. Mohammad Razali A, Tang SF, Syed Zakaria SZ, Che-Hamzah J, Aung T, Othman O, et al.
    Ophthalmic Res, 2023;66(1):854-861.
    PMID: 36917970 DOI: 10.1159/000530072
    INTRODUCTION: The aim of this study was to assess the effect of phacoemulsification and endo-cyclophotocoagulation (phaco-ECP) on intraocular pressure (IOP) fluctuation as assessed by the water drinking test (WDT) in primary open angle glaucoma (POAG).

    METHODS: This was a prospective observational study carried out at a tertiary referral centre. POAG patients on topical antiglaucoma medications and planned for phaco-ECP were recruited. WDT was performed before surgery and 6 weeks postoperatively by drinking 10 mL/kg of water in 5 min followed by serial IOP by Goldmann applanation tonometry measurements at 15, 30, 45, and 60 min. Mean IOP, IOP fluctuation (difference between highest and lowest IOP), IOP reduction, and factors affecting IOP fluctuation were analysed.

    RESULTS: Twenty eyes from 17 patients were included. Baseline IOP was similar before (14.7 ± 2.7 mm Hg) and after (14.8 ± 3.4 mm Hg, p = 0.90) surgery. There was no difference in mean IOP (17.6 ± 3.4 mm Hg vs. 19.3 ± 4.7 mm Hg pre- and postoperative, respectively, p = 0.26) or peak IOP (19.37 ± 3.74 mm Hg vs. 21.23 ± 5.29 mm Hg, p = 0.25), albeit a significant reduction in IOP-lowering medications (2.2 ± 1.15 vs. 0.35 ± 0.93, p < 0.001) postoperatively. IOP fluctuation was significantly greater (6.4 ± 3.2 mm Hg vs. 4.6 ± 2.1 mm Hg, p = 0.015) with more eyes having significant IOP fluctuation of ≥6 mm Hg (11 eyes [55%] vs. 4 eyes [20%], p < 0.001) postoperatively. Factors that were significantly associated with increased postoperative IOP fluctuations were higher preoperative IOP fluctuation (β = 0.69, 95% CI 0.379-1.582, p = 0.004) and more number of postoperative antiglaucoma medications (β = 0.627, 95% CI 0.614-3.322, p = 0.008).

    CONCLUSION: Reducing aqueous production with phaco-ECP does not eliminate IOP fluctuation in POAG patients. The increase in postoperative IOP fluctuation suggests increased outflow resistance after phaco-ECP.

  16. Azize NA, Ngah WZ, Othman Z, Md Desa N, Chin CB, Md Yunus Z, et al.
    J Hum Genet, 2014 Nov;59(11):593-7.
    PMID: 25231368 DOI: 10.1038/jhg.2014.69
    Glycine encephalopathy (GCE) or nonketotic hyperglycinemia is an inborn error of glycine metabolism, inherited in an autosomal recessive manner due to a defect in any one of the four enzymes aminomethyltransferase (AMT), glycine decarboxylase (GLDC), glycine cleavage system protein-H (GCSH) and dehydrolipoamide dehydrogenase in the glycine cleavage system. This defect leads to glycine accumulation in body tissues, including the brain, and causes various neurological symptoms such as encephalopathy, hypotonia, apnea, intractable seizures and possible death. We screened 14 patients from 13 families with clinical and biochemical features suggestive of GCE for mutation in AMT, GLDC and GCSH genes by direct sequencing and genomic rearrangement of GLDC gene using a multiplex ligation-dependant probe amplification. We identified mutations in all 14 patients. Seven patients (50%) have biallelic mutations in GLDC gene, six patients (43%) have biallelic mutations in AMT gene and one patient (7%) has mutation identified in only one allele in GLDC gene. Majority of the mutations in GLDC and AMT were missense mutations and family specific. Interestingly, two mutations p.Arg265His in AMT gene and p.His651Arg in GLDC gene occurred in the Penan sub-population. No mutation was found in GCSH gene. We concluded that mutations in both GLDC and AMT genes are the main cause of GCE in Malaysian population.
  17. Lau SC, Azim E, Abdul Latiff Z, Syed Zakaria SZ, Wong SW, Wu LL, et al.
    Med J Malaysia, 2018 12;73(6):382-387.
    PMID: 30647208
    INTRODUCTION: A smooth transition of healthcare for young people with chronic illnesses from paediatric to adult healthcare services is important to ensure optimal outcome. At the moment, there are no standard guidelines to assess a patient's readiness to transfer care.

    METHODS: A cross-sectional study using a self-administered questionnaire, adapted from UNC (University of North Carolina) TRxANSITION self-assessment tool was conducted to evaluate patients' transition care readiness in paediatric haematology and paediatric diabetes clinic.

    RESULTS: A total of 80 patients (37 thalassaemia and 43 diabetes) with the mean age of 21.2 (SD±4.3) years, were recruited during the 3-month study period. Majority of the patients have basic knowledge regarding their medications, and were able to comply with their follow-up. The mean total score obtained by the respondents on this questionnaire was 15.3 (SD±3.59). Self-management skills and knowledge on disease were the two poorly scored section; with mean score of 3.78 (SD±1.38) and 4.28 (SD±1.20) respectively. Overall, only 21 (26.2%) respondents obtained high score (score above 75th percentile). Seventy-five percent of the respondents admitted that they were not ready for transfer to an adult healthcare service yet at the time of the study.

    CONCLUSION: We suggest that patients with high score should be prepared for transition to adult facility whereas those with a low score need to be identified to ensure provision of continuous education.
  18. Borhanuddin B, Mohd Nawi A, Shah SA, Abdullah N, Syed Zakaria SZ, Kamaruddin MA, et al.
    ScientificWorldJournal, 2018;2018:2979206.
    PMID: 30111990 DOI: 10.1155/2018/2979206
    Cardiovascular disease (CVD) leads to high morbidity and mortality rate worldwide. Therefore, it is important to determine the risk of CVD across the sociodemographic factors to strategize preventive measures. The current study consisted of 53,122 adults between the ages of 35 and 65 years from The Malaysian Cohort project during recruitment phase from year 2006 to year 2012. Sociodemographic profile and physical activity level were assessed via self-reported questionnaire, whereas relevant CVD-related biomarkers and biophysical variables were measured to determine the Framingham Risk Score (FRS). The main outcome was the 10-year risk of CVD via FRS calculated based on lipid profile and body mass index (BMI) associated formulae. The BMI-based formula yielded a higher estimation of 10-year CVD risk than the lipid profile-based formula in the study for both males (median = 13.2% and 12.7%, respectively) and females (median = 4.3% and 4.2%, respectively). The subgroup with the highest risk for 10-year CVD events (based on both FRS formulae) was the Malay males who have lower education level and low physical activity level. Future strategies for the reduction of CVD risk should focus on screening via BMI-based FRS in this at-risk subpopulation to increase the cost-effectiveness of the prevention initiatives.
    Study name: The Malaysian Cohort (TMC) project
  19. Jamal R, Syed Zakaria SZ, Kamaruddin MA, Abd Jalal N, Ismail N, Mohd Kamil N, et al.
    Int J Epidemiol, 2015 Apr;44(2):423-31.
    PMID: 24729425 DOI: 10.1093/ije/dyu089
    The Malaysian Cohort study was initiated in 2005 by the Malaysian government. The top-down approach to this population-based cohort study ensured the allocation of sufficient funding for the project which aimed to recruit 100,000 individuals aged 35-70 years. Participants were recruited from rural and urban areas as well as from various socioeconomic groups. The main objectives of the study were to identify risk factors, to study gene-environment interaction and to discover biomarkers for the early detection of cancers and other diseases. At recruitment, a questionnaire-based interview was conducted, biophysical measurements were performed and biospecimens were collected, processed and stored. Baseline investigations included fasting blood sugar, fasting lipid profile, renal profile and full blood count. From April 2006 to the end of September 2012 we recruited a total of 106,527 participants. The baseline prevalence data showed 16.6% participants with diabetes, 46.5% with hypertension, 44.9% with hypercholesterolaemia and 17.7% with obesity. The follow-up phase commenced in June 2013. This is the most comprehensive and biggest cohort study in Malaysia, and has become a valuable resource for epidemiological and biological research. For information on collaboration and also data access, investigators can contact the project leader at (rahmanj@ppukm.ukm.edu.my).
    Study name: The Malaysian Cohort (TMC) project
  20. Kamal Rodin NS, Ismail NA, Abdul Wahid SF, Jamil A, Syed Zakaria SZ, Syed Abd Kadir SS, et al.
    Malays J Pathol, 2021 Dec;43(3):361-373.
    PMID: 34958057
    INTRODUCTION: The epidemiology of cutaneous graft versus host disease (GVHD) in allogeneic peripheral blood stem cell transplantation (PBSCT) in Malaysia has not been described.

    MATERIALS AND METHODS: We retrospectively analysed 691 allogeneic PBSCT patients between 2010-2017 in two centers.

    RESULTS: The prevalence of cutaneous GVHD was 31.4% (217/691). No associations were detected with race, age or gender of donor and recipients. Cutaneous GVHD was associated with host cytomegalovirus (CMV) seropositivity (p<0.01), conditioning (p<0.01), GVHD prophylaxis (p=0.046) and survival (p<0.01). Majority developed the acute form (58.1%;126/217). Biopsies in 20.7% (45/217) showed 55.6% positivity for GVHD. Overall, involvement was non-severe. A majority demonstrated complete response (CR) to first-line corticosteroids (70.0%;152/217). Secondline therapies (extracorporeal phototherapy (ECP), psolaren ultraviolet A (PUVA), mycophenolate, tumour necrosis factor (TNF) inhibitors, interleukins inhibitors, or CD20 monoclonal antibodies) were required in 65/217, with 38.5% CR. Second-line therapy was associated with gender (p=0.042), extra-cutaneous GVHD (p=0.021), treatment outcomes (p=0.026) and survival (p=0.048). Mortality in cutaneous GVHD was 24.0% with severe sepsis being the leading cause at Day 100 (7.8%) and 5-years (7.8%), and relapsed disease at 2-years (32.7%). In steroid refractoriness, severe GVHD caused 30.8% mortality. In cutaneous GVHD, survival at Day 100 was 95.4%; 80.2% at 2-years and 73.1% at 5-years. The median survival in cutaneous GVHD was significantly shorter at 55 months, compared to those without GVHD at 69 months (p=0.001).

    CONCLUSION: Cutaneous involvement is the commonest clinical manifestation of GVHD. A larger national study is warranted to further analyse severity and outcome of multiorgan GVHD, and factors associated with steroid refractoriness.

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