Displaying publications 1 - 20 of 41 in total

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  1. Lee YL, Ting TH, Lim CT, Thilakavathy K, Musa NH, Ling KH
    PMID: 38647408 DOI: 10.4274/jcrpe.galenos.2024.2023-12-1
    IGSF1 mutation is the commonest cause of mild to moderate isolated central congenital hypothyroidism and has an X-linked recessive inheritance, primarily affecting males. Other notable clinical features are macroorchidism with delayed pubertal testosterone rise, large birth weight, increased body mass index, low prolactin, transient growth hormone deficiency and low prolactin. Two male siblings with central hypothyroidism were found to have a novel IGSF1 c.3467T>A variant that was likely pathogenic based on the family segregation study. The proband, aged 3 years presented at 18 days old with prolonged jaundice while his 16-year-old brother was only detected to have central hypothyroidism after the proband's genetic analysis result was known. Both siblings were obese, had large birth weights, macroorchidism and low prolactin. The proband's brother had intellectual disability while the proband had normal development. This case study highlights the importance of evaluation for the IGSF1 variant in patients with unexplained central hypothyroidism, especially when accompanied by X-linked inheritance and macroorchidism. Family segregation analysis allows detection of other affected family members or carriers who may also benefit from thyroxine treatment.
  2. Lee YL, Jaafar NR, Ling JG, Huyop F, Abu Bakar FD, Rahman RA, et al.
    Int J Biol Macromol, 2024 Apr;263(Pt 1):130284.
    PMID: 38382786 DOI: 10.1016/j.ijbiomac.2024.130284
    Polyethylene terephthalate (PET) is one of the most produced plastics globally and its accumulation in the environment causes harm to the ecosystem. Polyethylene terephthalate hydrolyse (PETase) is an enzyme that can degrade PET into its monomers. However, free PETase lacks operational stabilities and is not reusable. In this study, development of cross-linked enzyme aggregate (CLEA) of PETase using amylopectin (Amy) as cross-linker was introduced to solve the limitations of free PETase. PETase-Amy-CLEA exhibited activity recovery of 81.9 % at its best immobilization condition. Furthermore, PETase-Amy-CLEA exhibited 1.37-, 2.75-, 2.28- and 1.36-fold higher half-lives than free PETase at 50 °C, 45 °C, 40 °C and 35 °C respectively. Moreover, PETase-Amy-CLEA showed broader pH stability from pH 5 to 10 and could be reused up to 5 cycles. PETase-Amy-CLEA retained >70 % of initial activity after 40 days of storage at 4 °C. In addition, lower Km of PETase-Amy-CLEA indicated better substrate affinity than free enzyme. PETase-Amy-CLEA corroded PET better and products yielded was 66.7 % higher than free PETase after 32 h of treatment. Hence, the enhanced operational stabilities, storage stability, reusability and plastic degradation ability are believed to make PETase-Amy-CLEA a promising biocatalyst in plastic degradation.
  3. Liew JES, Chong Cheng Y, Tai NL, Pereira A, Manivannan V, Khoo SL, et al.
    Int J Pharm Pract, 2024 Feb 15;32(1):83-90.
    PMID: 38289996 DOI: 10.1093/ijpp/riad083
    OBJECTIVES: This study aimed to evaluate the effectiveness of workflow redesign (eaST system) on pharmacy waiting time and near-missed events. We also investigated other factors that may potentially affect these study outcomes.

    METHODS: A quasi-experimental (before-after) study design was adopted. Pre-intervention data were collected over 7 months (January-July 2017). Subsequently, the workflow redesign (eaST system) was implemented and the effect of the intervention (August 2017-February 2018) was evaluated. Univariate analysis was used to compare the differences between pre-intervention and post-intervention of pharmacy waiting time and near-missed events. Significant factors affecting study outcomes were analysed using linear regression analysis.

    KEY FINDINGS: A total of 210,530 prescriptions were analysed. The eaST system significantly increases the percentage of prescriptions dispensed within 30 min per day (median = 68 (interquartile range (IQR) = 41) vs. median = 93 (IQR = 33), P < 0.001) and reduced the mean percentage of near-missed events (mean = 50.71 (standard deviation (SD) = 23.95) vs. mean = 27.87 (SD = 12.23), P < 0.001). However, the eaST system's effects on related outcomes were conditional on a three-way interaction effect. The eaST system's effects on pharmacy waiting time were influenced by the number of prescriptions received and the number of PhIS server disruptions. Conversely, the eaST system's effects on near-missed events were influenced by the number of pharmacy personnel and number of controlled medications.

    CONCLUSIONS: Overall, the eaST system improved the pharmacy waiting time and reduced near-missed events.

  4. Lee YL, Nasir FFWA, Selveindran NM, Zaini AA, Lim PG, Jalaludin MY
    Diabetes Res Clin Pract, 2023 Nov;205:110981.
    PMID: 37890700 DOI: 10.1016/j.diabres.2023.110981
    AIMS: Despite emerging evidence of increased paediatric diabetes mellitus (DM) and diabetic ketoacidosis (DKA) worldwide following the COVID-19 pandemic, studies in Asia are lacking. We aimed to determine the frequency, demographics, and clinical characteristics of new onset type 1 DM (T1DM) during the pandemic in Malaysia.

    METHODS: This is a retrospective multicenter study involving new onset T1DM paediatric patients in Klang Valley, Malaysia during two time periods ie 18th September 2017-17th March 2020 (pre-pandemic) and 18th March 2020-17th September 2022 (pandemic).

    RESULTS: There was a total of 180 patients with new onset T1DM during the 5-year study period (71 pre-pandemic, 109 pandemic). An increase in frequency of T1DM was observed during the pandemic (52 in 2021, 38 in 2020, 27 in 2019 and 30 in 2018). A significantly greater proportion of patients presented with DKA (79.8 % vs 64.8 %), especially severe DKA (46.8 % vs 28.2 %) during the pandemic. Serum glucose was significantly higher (28.2 mmol vs 25.9 mmol/L) with lower venous pH (7.10 vs 7.16), but HbA1c was unchanged.

    CONCLUSIONS: New onset T1DM increased during the pandemic, with a greater proportion having severe DKA. Further studies are required to evaluate the mechanism leading to this rise to guide intervention measures.

  5. Lee YL, Ting TH, Lim CT, Arrumugam-Arthini C, Karuppiah T, Ling KH
    J Pediatr Endocrinol Metab, 2023 Oct 26;36(10):988-992.
    PMID: 37621150 DOI: 10.1515/jpem-2023-0171
    OBJECTIVES: PAX4 (Paired box 4), a transcription factor crucial in pancreatic beta cell development and function, is a rare cause of maturity-onset diabetes of the young (MODY). What is new? A novel PAX4 variant is verified by family segregation study to be likely pathogenic. A child below 10 years of age diagnosed to have PAX4-MODY, differing from previously reported paediatric cases diagnosed in adolescence.

    CASE PRESENTATION: A child with diabetes diagnosed at age 8 years, harbored a PAX4 variant, c.890G>A (p.Gly297Asp), initially classified as variant of uncertain significance. Eleven family members (7 adults and 4 children) with and without diabetes across 3 generations were genotyped. The variant co-segregated with diabetes or prediabetes across 3 generations of the family. The variant is reclassified as likely pathogenic according to standard guidelines.

    CONCLUSIONS: Genetic testing is essential to confirm PAX4-MODY as the presentation is variable even within the same family. PAX4 mutation needs to be considered in MODY genetic testing in Asian patients.

  6. Lee YL, Zaini AA, Idris AN, Abdullah RA, Wong JS, Hong JS, et al.
    J Paediatr Child Health, 2023 Jul;59(7):879-884.
    PMID: 37066819 DOI: 10.1111/jpc.16405
    AIMS: Knowledge on the spectrum of thyroid disorders amongst Turner syndrome (TS) patients in Southeast Asia is limited. This study aimed to evaluate the prevalence of thyroid autoimmunity, the spectrum of autoimmune thyroid disease and association with age and karyotype amongst Malaysian TS girls.

    METHODS: A cross-sectional study was conducted at 11 paediatric endocrine units in Malaysia. Blood samples for antithyroglobulin antibodies, antithyroid peroxidase antibodies and thyroid function test were obtained. In patients with pre-existing thyroid disease, information on clinical and biochemical thyroid status was obtained from medical records.

    RESULTS: Ninety-seven TS patients with a mean age of 13.4 ± 4.8 years were recruited. Thyroid autoimmunity was found in 43.8% of TS patients. Nineteen per cent of those with thyroid autoimmunity had autoimmune thyroid disease (Hashimoto thyroiditis in 7.3% and hyperthyroidism in 1% of total population). Patients with isochromosome X and patients with 45,X mosaicism or other X chromosomal abnormalities were more prone to have thyroid autoimmunity compared to those with 45,X karyotype (OR 5.09, 95% CI 1.54-16.88, P = 0.008 and OR 3.41, 95% CI 1.32-8.82, P = 0.01 respectively). The prevalence of thyroid autoimmunity increased with age (33.3% for age 0-9.9 years; 46.8% for age 10-19.9 years and 57.1% age for 20-29.9 years) with autoimmune thyroid disease detected in 14.3% during adulthood.

    CONCLUSION: Thyroid autoimmunity was significantly associated with the non 45,X karyotype group, particularly isochromosome X. Annual screening of thyroid function should be carried out upon diagnosis of TS until adulthood with more frequent monitoring recommended in the presence of thyroid autoimmunity.

  7. Liam CCK, Tiao JY, Yap YY, Lee YL, Sathar J, McRae S, et al.
    Blood Res, 2023 Mar 31;58(1):36-41.
    PMID: 36632683 DOI: 10.5045/br.2023.2022133
    BACKGROUND: The PLASMIC score is a convenient tool for predicting ADAMTS13 activity of <10%. Lactate dehydrogenase (LDH) is widely used as a marker of haemolysis in thrombotic thrombocytopenic purpura (TTP) monitoring, and could be used as a replacement marker for lysis. We aimed to validate the PLASMIC score in a multi-centre Asia Pacific region, and to explore whether LDH could be used as a replacement marker for lysis.

    METHODS: Records of patients with thrombotic microangiopathy (TMA) were reviewed. Patients' ADAMTS13 activity levels were obtained, along with clinical/laboratory findings relevant to the PLASMIC score. Both PLASMIC scores and PLASMIC-LDH scores, in which LDH replaced traditional lysis markers, were calculated. We generated a receiver operator characteristics (ROC) curve and compared the area under the curve values (AUC) to determine the predictive ability of each score.

    RESULTS: 46 patients fulfilled the inclusion criteria, of which 34 had ADAMTS13 activity levels of <10%. When the patients were divided into intermediate-to-high risk (scores 5‒7) and low risk (scores 0‒4), the PLASMIC score showed a sensitivity of 97.1% and specificity of 58.3%, with a positive predictive value (PPV) of 86.8% and negative predictive value (NPV) of 87.5%. The PLASMIC-LDH score had a sensitivity of 97.1% and specificity of 33.3%, with a PPV of 80.5% and NPV of 80.0%.

    CONCLUSION: Our study validated the utility of the PLASMIC score, and demonstrated PLASMIC-LDH as a reasonable alternative in the absence of traditional lysis markers, to help identify high-risk patients for treatment via plasma exchange.

  8. Azmi JA, C Thambiah S, Lee YL, Zahari Sham SY, Abdul Hamid H, Samsudin IN
    J Paediatr Child Health, 2023 Jan;59(1):185-187.
    PMID: 36222293 DOI: 10.1111/jpc.16243
  9. Loh GOK, Wong EYL, Goh CZ, Tan YTF, Lee YL, Pang LH, et al.
    Ann Med, 2023;55(2):2270502.
    PMID: 37857359 DOI: 10.1080/07853890.2023.2270502
    The study aimed to develop a sensitive and high-throughput liquid chromatography coupled with tandem mass spectrometry method to quantify concentrations of tramadol and paracetamol simultaneously in human plasma. Sample preparation involved single-step protein precipitation using methanol and two deuterated internal standards, tramadol D6 and paracetamol D4. Agilent Poroshell 120 EC-C18 (100 × 2.1 mm, 2.1 µm) analytical column was employed to achieve chromatographic separation. Detection was in positive ion multiple reaction monitoring mode. A tailing factor (Tf) of <1.2, separation factor (K prime) of >1.5 from the column dead time and signal-to-noise (S/N) ratio >10, were obtained for analytes and internal standards. The standard curve was linear over the concentration range of 2.5-500.00 ng/mL for tramadol and 0.025-20.00 μg/mL for paracetamol. A small injection volume of 1 µL, low flow rate of 440 µL/min and short analysis time of 3.5 min reduced the solvent consumption, analysis cost and system contamination. The results of method validation parameters fulfilled the acceptance criteria of bioanalytical guidelines. The method was successfully applied to a bioequivalence study of fixed-dose combination products of tramadol and paracetamol in Malaysian healthy subjects.
  10. Lai MY, Bukhari FDM, Zulkefli NZ, Ismail I, Mustapa NI, Soh TST, et al.
    Int J Infect Dis, 2022 Jul;120:132-134.
    PMID: 35472524 DOI: 10.1016/j.ijid.2022.04.036
    OBJECTIVES: Preventing reverse transcription loop-mediated isothermal amplification (RT-LAMP) carryover contamination could be solved by adding deoxyuridine triphosphate (dUTP) and uracil-DNA glycosylase (UDG) into the reaction master mix.

    METHODS: RNA was extracted from nasopharyngeal swab samples by a simple RNA extraction method.

    RESULTS: Testing of 77 samples demonstrated 91.2% sensitivity (95% confidence interval [CI]: 78-98.2%) and 100% specificity (95% confidence interval: 92-100%) using UDG RT-LAMP.

    CONCLUSION: This colorimetric UDG RT-LAMP is a simple-to-use, fast, and easy-to-interpret method, which could serve as an alternative for diagnosis of SARS-CoV-2 infection, especially in remote hospitals and laboratories with under-equipped medical facilities.

  11. Lai MY, Suppiah J, Thayan R, Ismail I, Mustapa NI, Soh TST, et al.
    Trop Med Health, 2022 Jan 04;50(1):2.
    PMID: 34980275 DOI: 10.1186/s41182-021-00396-y
    BACKGROUND: Current diagnosis of SARS-CoV-2 infection relies on RNA purification prior to amplification. Typical extraction methods limit the processing speed and turnaround time for SARS-CoV-2 diagnostic testing.

    METHODS: Here, we applied reverse transcription loop-mediated isothermal amplification directly onto human clinical swabs samples to amplify the RNA from SARS-CoV-2 swab samples after processing with chelating resin.

    RESULTS: By testing our method on 64 samples, we managed to develop an RT-LAMP assay with 95.9% sensitivity (95% CI 86 to 99.5%) and 100% specificity (95% CI 78.2-100%).

    CONCLUSION: The entire process including sample processing can be completed in approximately 50 min. This method has promising potential to be applied as a fast, simple and inexpensive diagnostic tool for the detection of SARS-CoV-2.

  12. Lee YL, Islam T, Danaee M, Taib NA, MyBCC study group
    PLoS One, 2022;17(11):e0277982.
    PMID: 36409745 DOI: 10.1371/journal.pone.0277982
    Regular physical activity (PA) after a breast cancer diagnosis is associated with reduced mortality and better quality of life. In this prospective cohort study, we aimed to explore the trends of PA among breast cancer survivors over three years and identify factors associated with low PA. Interviews on 133 breast cancer patients were conducted at baseline, one and three years after the diagnosis of breast cancer at University Malaya Medical Centre in Kuala Lumpur. Physical activity was measured by using the Global Physical Activity Questionnaire. PA was categorised as active (≥ 600 MET-min/week) and inactive (<600 MET-min/week). We used the generalised estimating equation method to examine PA levels and factors affecting PA longitudinally. The survivors' mean age was 56.89 (±10.56) years; half were Chinese (50.4%), and 70.7% were married. At baseline, 48.1% of the patients were active, but the proportion of active patients declined to 39.8% at one year and 35.3% in the third year. The mean total PA decreased significantly from 3503±6838.3 MET-min/week to 1494.0±2679.8 MET-min/week (one year) and 792.5±1364 MET-min/week (three years) (p<0.001). Three years after diagnosis (adjusted odds ratio [AOR]: 1.74, p = 0.021); Malay ethnicity (AOR: 1.86, p = 0.042) and being underweight (AOR: 3.43, p = 0.004) were significantly associated with inactivity. We demonstrated that breast cancer survivors in Malaysia had inadequate PA levels at diagnosis, which decreased over time. Thus, it is vital to communicate about the benefits of PA on cancer outcomes and continue to encourage breast cancer survivors to be physically active throughout the extended survivorship period, especially in the Malay ethnic group and underweight patients.
  13. Lai MY, Bukhari FDM, Zulkefli NZ, Ismail I, Mustapa NI, Soh TST, et al.
    BMC Infect Dis, 2021 Nov 17;21(1):1162.
    PMID: 34789179 DOI: 10.1186/s12879-021-06876-0
    BACKGROUND: Current assays for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rely on time consuming, costly and laboratory based methods for virus isolation, purification and removing inhibitors. To address this limitation, we propose a simple method for testing RNA from nasopharyngeal swab samples that bypasses the RNA purification step.

    METHODS: In the current project, we have described two extraction-free reverse transcription loop-mediated isothermal amplification (RT-LAMP) assays for the detection of SARS-CoV-2 by using E gene and RdRp gene as the targets.

    RESULTS: Here, results showed that reverse transcription loop-mediated isothermal amplification assays with 88.4% sensitive (95% CI: 74.9-96.1%) and 67.4% sensitive (95% CI: 51.5-80.9%) for E gene and RdRp gene, respectively.

    CONCLUSION: Without the need of RNA purification, our developed RT-LAMP assays for direct detection of SARS-CoV-2 from nasopharyngeal swab samples could be turned into alternatives to qRT-PCR for rapid screening.

  14. Kit Loh GO, Ling Wong EY, Fung Tan YT, Lee YL, Chew CK, Mohd Sali ND, et al.
    Bioanalysis, 2021 Nov 08.
    PMID: 34743613 DOI: 10.4155/bio-2021-0185
    Aim: To develop an LC-MS/MS method for simultaneous determination of duloxetine and its metabolite, 4-hydroxy duloxetine glucuronide (4HDG) in human plasma and to investigate the potential back-conversion of 4HDG to duloxetine using stability study. Materials & methods: The LC-MS/MS method was validated according to the EMA and USFDA Bioanalytical Method Validation Guidelines and applied to pilot bioequivalence study. Results & conclusion: The method validation results were within the acceptance limits. The stability study and incurred sample reanalysis results ruled out the occurrence of back-conversion. The study highlighted the conduct of back-conversion test and the advantages of LC-MS/MS method in terms of sensitivity, specificity and low consumption of organic solvents.
  15. Woon YL, Lee YL, Chong YM, Ayub NA, Krishnabahawan SL, Lau JFW, et al.
    Lancet Reg Health West Pac, 2021 Apr;9:100123.
    PMID: 33778796 DOI: 10.1016/j.lanwpc.2021.100123
    Background: Asymptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections are well documented. Healthcare workers (HCW) are at increased risk of infection due to occupational exposure to infected patients. We aim to determine the prevalence of SARS-CoV-2 antibodies among HCW who did not come to medical attention.

    Methods: We prospectively recruited 400 HCW from the National Public Health Laboratory and two COVID-19 designated public hospitals in Klang Valley, Malaysia between 13/4/2020 and 12/5/2020. Quota sampling was used to ensure representativeness of HCW involved in direct and indirect patient care. All participants answered a self-administered questionnaire and blood samples were taken to test for SARS-CoV-2 antibodies by surrogate virus neutralization test.

    Findings: The study population comprised 154 (38.5%) nurses, 103 (25.8%) medical doctors, 47 (11.8%) laboratory technologists and others (23.9%). A majority (68.9%) reported exposure to SARS-CoV-2 in the past month within their respective workplaces. Adherence to personal protection equipment (PPE) guidelines and hand hygiene were good, ranging from 91-100% compliance. None (95% CI: 0, 0.0095) of the participants had SARS-CoV-2 antibodies detected, despite 182 (45.5%) reporting some symptoms one month prior to study recruitment. One hundred and fifteen (29%) of participants claimed to have had contact with known COVID-19 persons outside of their workplace.

    Interpretation: Zero seroprevalence among HCW suggests a low incidence of undiagnosed COVID-19 infection in our healthcare setting during the first local wave of SARS-CoV-2 infection. The occupational risk of SARS-CoV-2 transmission within healthcare facilities can be prevented by adherence to infection control measures and appropriate use of PPE.

  16. Liam CCK, Boo YL, Lee YL, Law KB, Ho KW, Shahnaz SAKS, et al.
    Blood Cell Ther, 2021 Feb 25;4(1):1-8.
    PMID: 36712843 DOI: 10.31547/bct-2020-009
    BACKGROUND: Multiple Myeloma (MM) is characterized by the presence of clonal plasma cells. These often result in complications including bone destruction, hypercalcemia, renal insufficiency, and anaemia. Induction with a triplet or quadruplet regimen followed by autologous stem cell transplantation (ASCT) has been the standard of care for transplant eligible patients to achieve durable remission.

    PURPOSE: This is a retrospective analytical study to determine the outcome of Multiple Myeloma patients who underwent ASCT in Ampang Hospital.

    MATERIALS AND METHODS: We included a 5-year cohort of patients transplanted from 1st July 2014 to 30th June 2019. Data were obtained through electronic medical records. Prognostic factors for progression-free survival (PFS) and overall survival (OS) were analyzed using simple and multiple Cox proportional hazard regression analysis. All analyses were done using software R version 3.6.2 with validated statistical packages.

    RESULTS: 139 patients were analyzed. The median age at transplant was 56 years old and 56.1% are males (n=78). The most common subtype is IgG Kappa (n=67, 48.2%). Only 93 patients in which the International Staging System (ISS) could be determined, and among them, 33.3% of patients (n=31) have advanced stage Ⅲ disease. The most common induction received before ASCT was a bortezomib based regimen and/or an immunomodulatory (IMiD) based regimen. 63.3% of patients achieved at least a very good partial response (VGPR) before ASCT. Most patients received myeloablative conditioning (MAC) (n=119, 85.6%). The mean cell dose is 3.68×106/kg. The median time to engraftment was 11 days for both platelet and absolute neutrophil count (ANC). With the median follow-up of 17.3 (range, 6.2-33.4) months, the median OS and PFS were not reached. The 1-year and 2-year PFS were 75% (95% CI 66-82%) and 52% (95% CI 42-62%), respectively. The 1-year and 2-year OS were 82% (95% CI 74-88%) and 70% (95% CI 60-78%), respectively. 6 patients (4.3%) had transplant-related mortality (TRM). IgA subtype was found to adversely affect PFS. Maintenance therapy and the absence of renal impairment was associated with better PFS and OS.

    DISCUSSION AND CONCLUSIONS: Our study found that ASCT following induction treatment is safe and beneficial to achieve a deeper remission status. In our study, the addition of maintenance therapy is associated with an improved outcome in PFS and OS.

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