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  1. Tan, XC, M Makmor-Bakry, Lau, CL, Tajarudin, FW, Raymond, AA
    Neurology Asia, 2015;20(3):235-241.
    MyJurnal
    Poor adherence to antiepileptic drug (AED) therapy can lead to various undesirable complications. Identifying the contributing factors of poor adherence is beneficial in assisting health care professionals to provide optimal interventions to control the seizures. This study aimed to identify the prevalence and factors affecting the adherence level to AED therapy in a multiracial population with epilepsy. This cross-sectional study was conducted at the neurology clinic of a tertiary care setting. Researcher-assisted questionnaire was utilised. Adherence level was assessed using validated Modified Morisky Adherence Scale-8. A total of 145 patients with epilepsy were included in this study. The prevalence of poor adherence to AED therapy was 64.1%. Poor adherence level was significantly associated with younger age (χ2 = 7.609, p = 0.022), medication adverse effects (χ2 = 5.075, p = 0.020), shorter duration of epilepsy (r = 0.180, p = 0.030) and uncertainty about the necessity for AEDs (χ2 = 11.803, p = 0.001).
    Conclusion, prevalence of poor adherence to antiepileptic drugs was high and factors associated with poor adherence to AEDs were identified for a multiracial population with epilepsy.
    Study site: Neurology clinic, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
  2. Cheong JY, Makmor-Bakry M, Lau CL, Abdul Rahman R
    S. Afr. Med. J., 2012 Jul;102(7):616-9.
    PMID: 22748440
    The incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections in intensive care units in Malaysia is significant. Invasive MRSA infections are commonly treated with vancomycin. In clinical practice, the serum vancomycin trough concentration is used as a surrogate marker of vancomycin efficacy. A low concentration of vancomycin may result in less effective therapy and increase the risk of bacterial resistance. We evaluated the relationship between the resolution of MRSA infections and trough concentrations of vancomycin.
  3. Makmor-Bakry M, Ahmat A, Shamsuddin A, Lau CL, Ramli R
    Anaesthesiol Intensive Ther, 2019;51(3):218-223.
    PMID: 31434472 DOI: 10.5114/ait.2019.87362
    BACKGROUND: Failure of antibiotic treatment increases mortality of critically ill patients. This study investigated the association between the treatment resolution of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and vancomycin pharmacokinetic variables.

    METHODS: A total of 28 critically ill patients were included in this study. All data were collected from medical, microbiology and pharmacokinetic records. The clinical response was evaluated on the basis of clinical and microbiological parameters. The 24-h area under the curve (AUC0-24) was estimated from a single trough level using established equations.

    RESULTS: Out of the 28 patients, 46% were classified as responders to vancomycin treatment. The trough vancomycin concentration did not differ between the responders and non-responders (15.02 ± 6.16 and 14.83 ± 4.80 μg mL-1; P = 0.929). High vancomycin minimum inhibitory concentration (MIC) was observed among the non-responders (P = 0.007). The ratio between vancomycin trough concentration and vancomycin MIC was significantly lower in the non-responder group (8.76 ± 3.43 vs. 12.29 ± 4.85 μg mL-1; P = 0.034). The mean ratio of estimated AUC0-24 and vancomycin MIC was 313.78 ± 117.17 μg h mL-1 in the non-responder group and 464.44 ± 139.06 μg h mL-1 in the responder group (P = 0.004). AUC0-24/MIC of ≥ 400 μg h mL-1 was documented for 77% of the responders and 27% of the non-responders (c2 = 7.03; P = 0.008).

    CONCLUSIONS: Ratio of trough concentration/MIC and AUC0-24/MIC of vancomycin are better predictors for MRSA treatment outcomes than trough vancomycin concentration or AUC0-24 alone. The single trough-based estimated AUC may be sufficient for the monitoring of treatment response with vancomycin.

  4. Chan KY, Lau CL, Adeeb SM, Somasundaram S, Nasir-Zahari M
    Plast Reconstr Surg, 2005 Sep 15;116(4):1013-20; discussion 1021-2.
    PMID: 16163087
    BACKGROUND: Hypertrophic scarring caused by sternotomy is prevalent among Asians. The effectiveness of silicone gel in scar prevention may influence the decision of surgeons and patients regarding its routine use during the postoperative period.

    METHODS: The authors conducted a randomized, placebo-controlled, double-blind, prospective clinical trial. The susceptibility to scar development varied among patients; therefore, sternal wounds were divided into the upper half and the lower half. Two types of coded gel prepared by an independent pharmacist were used on either half. Thus, selection and assessment biases and confounders were eliminated.

    RESULTS: One hundred wounds in 50 patients were randomized into two arms, 50 control and 50 silicone gels. The median age was 61 years and there were 34 men and 16 women. Ethnic distribution was 28 Malays, 18 Chinese, and four Indians. No side effect caused by the silicone gel was noted. Ninety-eight percent of patients had moderate to good compliance. The incidence of sternotomy scar was 94 percent. At the third month postoperatively, the silicone gel wounds were scored lower when compared with the control wounds. The differences were statistically significant in all parameters, including pigmentation (p = 0.02), vascularity (p = 0.001), pliability (p = 0.001), height (p = 0.001), pain (p = 0.001), and itchiness (p = 0.02).

    CONCLUSIONS: The effect of silicone gel in prevention of hypertrophic scar development in sternotomy wounds is promising. There are no side effects and patients' compliance is satisfactory. This study may popularize the use of silicone gel in all types of surgery to minimize the formation of hypertrophic scars in the early postoperative period.

  5. Teoh CY, Mhd Ali A, Mohamed Shah N, Hassan R, Lau CL
    JAC Antimicrob Resist, 2020 Sep;2(3):dlaa035.
    PMID: 34223001 DOI: 10.1093/jacamr/dlaa035
    Background: There is a paucity of data on pharmacists' competency and learning needs in antimicrobial stewardship (AMS).

    Objectives: To identify and prioritize learning needs based on self-perceived competence of ward pharmacists in AMS, to identify predictors of self-perceived competence, learning methods in AMS and perceived barriers to learning.

    Methods: A cross-sectional survey involving ward pharmacists from Hospital Canselor Tuanku Muhriz (HCTM) and hospitals under the Ministry of Health was conducted from May to July 2018.

    Results: A total of 553 ward pharmacists from 67 hospitals responded to this survey (71.3% response rate). Knowledge of infections, antimicrobials and AMS systems, confidence to advise on various issues relating to antimicrobial therapy and participation in clinical audit and evaluation were among the learning needs identified (median score 3.00). Meanwhile, knowledge on the epidemiology of infections, off-label use of antimicrobials and pharmacoeconomics relating to antimicrobials had lower median scores (2.00) and were thus prioritized as high learning needs. Significant predictors of self-perceived competence in AMS were: gender (P 

  6. Lau CL, Chan ST, Selvaratanam M, Khoo HW, Lim AY, Modamio P, et al.
    Fundam Clin Pharmacol, 2015 Aug;29(4):404-16.
    PMID: 26011058 DOI: 10.1111/fcp.12126
    Tyrosine kinase inhibitor sunitinib (used in GIST, advanced RCC, and pancreatic neuroendocrine tumors) undergoes CYP3A4 metabolism and is an ABCB1B and ABCG2 efflux transporters substrate. We assessed the pharmacokinetic interaction with ibuprofen (an NSAID used by patients with cancer) in Balb/c male and female mice. Mice (study group) were coadministered (30 min apart) 30 mg/kg of ibuprofen and 60 mg/kg of sunitinib PO and compared with the control groups, which received sunitinib alone (60 mg/kg, PO). Sunitinib concentration in plasma, brain, kidney, and liver was measured by HPLC as scheduled and noncompartmental pharmacokinetic parameters estimated. In female control mice, sunitinib AUC0→∞ decreased in plasma (P < 0.05), was higher in liver and brain (P < 0.001), and lower in kidney (P < 0.001) vs. male control mice. After ibuprofen coadministration, female mice showed lower AUC0→∞ in plasma (P < 0.01), brain, liver, and kidney (all P < 0.001). However, in male mice, AUC0→∞ remained unchanged in plasma, increased in liver and kidney, and decreased in brain (all P < 0.001). The tissue-to-plasma AUC0→∞ ratio was similar between male and female control mice, but changed after ibuprofen coadministration: Male mice showed 1.6-fold higher liver-to-plasma ratio (P < 0.001) while remained unchanged in female mice and in kidney (male and female mice) but decreased 55% in brain (P < 0.05). The tissue-to-plasma partial AUC ratio, the drug tissue targeting index, and the tissue-plasma hysteresis-like plots also showed sex-based ibuprofen-sunitinib drug interaction differences. The results illustrate the relevance of this DDI on sunitinib pharmacokinetics and tissue uptake. These may be due to gender-based P450 and efflux/transporters differences.
  7. Chong PS, Khairuddin S, Tse ACK, Hiew LF, Lau CL, Tipoe GL, et al.
    Sci Rep, 2020 09 10;10(1):14945.
    PMID: 32913245 DOI: 10.1038/s41598-020-71966-z
    Cerebellar ataxia is a neurodegenerative disorder with no definitive treatment. Although several studies have demonstrated the neuroprotective effects of Hericium erinaceus (H.E.), its mechanisms in cerebellar ataxia remain largely unknown. Here, we investigated the neuroprotective effects of H.E. treatment in an animal model of 3-acetylpyridine (3-AP)-induced cerebellar ataxia. Animals administered 3-AP injection exhibited remarkable impairments in motor coordination and balance. There were no significant effects of 25 mg/kg H.E. on the 3-AP treatment group compared to the 3-AP saline group. Interestingly, there was also no significant difference in the 3-AP treatment group compared to the non-3-AP control, indicating a potential rescue of motor deficits. Our results revealed that 25 mg/kg H.E. normalised the neuroplasticity-related gene expression to the level of non-3-AP control. These findings were further supported by increased protein expressions of pERK1/2-pCREB-PSD95 as well as neuroprotective effects on cerebellar Purkinje cells in the 3-AP treatment group compared to the 3-AP saline group. In conclusion, our findings suggest that H.E. potentially rescued behavioural motor deficits through the neuroprotective mechanisms of ERK-CREB-PSD95 in an animal model of 3-AP-induced cerebellar ataxia.
  8. Loong LS, Siew Mei Lai P, Jamaluddin NAH, Naina-Mohamed I, Periyasamy P, Lau CL, et al.
    J Infect Dev Ctries, 2022 Dec 31;16(12):1877-1886.
    PMID: 36753656 DOI: 10.3855/jidc.15925
    INTRODUCTION: Malaysia is an upper-middle-income country with national antimicrobial stewardship programs in place. However, hospitals in this country are faced with a high incidence of multidrug-resistant organisms and high usage of broad-spectrum antibiotics. Therefore, this study aimed to use a standardized audit tool to assess clinical appropriateness, guideline compliance, and prescribing patterns of antimicrobial use among medical patients in two tertiary hospitals in Malaysia to benchmark practice.

    METHODOLOGY: A prospective hospital-wide point prevalence survey was carried out by a multidisciplinary team in April 2019 at the University Malaya Medical Centre (UMMC) and the Hospital Canselor Tuanku Muhriz (HCTM), Kuala Lumpur, Malaysia. Data was collected from the patient's electronic medical records and recorded using the Hospital National Antimicrobial Prescribing Survey toolkit developed by the National Centre for Antimicrobial Stewardship, Australia.

    RESULTS: The appropriateness of prescriptions was 60.1% (UMMC) and 67% (HCTM), with no significant difference between the two hospitals. Compliance with guidelines was 60.0% (UMMC) and 61.5% (HCTM). Amoxicillin-clavulanic acid was the most commonly prescribed antimicrobial (UMMC = 16.9%; HCTM = 11.9%).

    CONCLUSIONS: The appropriateness of antimicrobial prescribing in medical wards, compliance with guidelines, and prescribing patterns were similar between the two hospitals in Malaysia. The survey identified several areas of prescribing that would need targeted AMS interventions.

  9. Zhu Y, Restrepo AC, Wang HB, Mills DJ, Liang RR, Liu ZB, et al.
    J Travel Med, 2024 Apr 09.
    PMID: 38591791 DOI: 10.1093/jtm/taae056
    BACKGROUND: Despite the World Health Organisation certifying China malaria-free in 2021, the risk of local transmission caused by imported malaria cases remains a significant clinical and public health issue. It is necessary to present the changing trends of malaria in China and discuss the role of travel medicine services in consolidating malaria elimination.

    METHODS: This study systematically reviewed articles and reports related to human malaria from 2013 to 2022 published in international and Chinese databases. Data on malaria (i.e. number of cases, Plasmodium spp., diagnostic method, country of acquisition, provinces with high risk of re-introduction and transmission) were collected and synthesised, then summarised using descriptive statistics.

    RESULTS: Overall, 24 758 cases of malaria (>99.5% laboratory confirmed, > 99.2% imported, 0.5% fatal) were reported in China from 2013 to 2022, with a downward trend over the years (4128 cases in 2013 compared to 843 cases in 2022; χ2 trend p-value = 0.005). The last locally acquired case was reported in 2017. P. falciparum (65.5%) was the most common species identified, followed by P. vivax (20.9%) and P. ovale (10.0%). Two Pheidole knowlesi cases were also identified in 2014 and 2017 in returned travellers from Malaysia and Indonesia, respectively. The most common countries of malaria acquisition were Ghana, Angola, and Myanmar. P. vivax was mainly detected in returned travellers from Myanmar, while P. falciparum and P. ovale were detected in travellers from Sub-Saharan Africa. Imported cases were mainly reported in Yunnan, Jiangsu, Sichuan, Guangxi, Shandong, Zhejiang, and Henan provinces, where large numbers of Chinese people travel overseas for work.

    CONCLUSION: Returned travellers from malaria-endemic countries pose a significant risk of malaria re-introduction to China. Travel medicine should be strengthened to improve the capacity and accessibility of both pre- and post-travel services, including malaria prophylaxis and prompt diagnosis of illness in returned travellers.

  10. Lau CL, Neoh HM, Periyasamy P, Tg Abu Bakar Sidik TMI, Tan TL, Ramli R, et al.
    Front Cell Infect Microbiol, 2024;14:1429830.
    PMID: 39512590 DOI: 10.3389/fcimb.2024.1429830
    BACKGROUND: Antimicrobial resistance (AMR) can lead to fatal consequences. AMR genes carriage by phenotypically susceptible bacteria, such as Extended-Spectrum β-Lactamases (ESBL)s in Enterobacteriaceae, have potential implications for AMR spread and therapeutic outcomes. This phenomenon should be investigated.

    METHODS: Positive blood cultures from hospitalized patients in a Malaysian tertiary center between April 2022 and March 2023 were reviewed. A total of 137 clinical isolates of Escherichia coli (E.coli), Klebsiella pneumoniae (K.pneumoniae), and Klebsiella oxytoca were included. The antibiotic susceptibility and ESBL phenotypes were determined by disk diffusion method and the identification of genotypes by multiplex polymerase chain reaction. The clinical characteristics and outcome information were extracted by reviewing patients' medical records to evaluate the clinical significance of the ESBL genotype-positive but phenotype-negative isolates in bacteremia.

    RESULTS: All 137 isolates were positive for at least one genotype (bla CTX-M, n = 71, 51.8%; bla SHV, n = 87, 63.5%; bla TEM, n = 95, 69.3%; bla OXA-1, n = 38, 27.7%). While bla CTX-M was proportionately higher in the ESBL phenotype-positive isolates than ESBL phenotype-negative isolates (33/37, 89.2% vs 38/100, 38%; p < 0.001), more than half of those harboring bla CTX-M remained susceptible to third-generation cephalosporins (3GC). The sensitivity (Sen) of bla CTX-M for ESBL phenotypes prediction was 89.19% (95% confidence interval [CI], 74.58 - 96.97%); however, specificity (Sp) was low (46.47%; 95% CI 39.75 - 53.32). The patient characteristics were similar among 98 ESBL phenotype-negative cases, except that the non-bla CTX-M carrier group had significantly more renal impairment (0/37 vs 7/61, p = 0.043) and gastrointestinal sources of bacteremia (9/37 vs 27/61, p = 0.047). No differences were observed in infection severity, in-hospital mortality, and length of stay (LOS) between the bla CTX-M and non-bla CTX-M carrier groups.

    CONCLUSION: The current study provides insight into the gene carriage in E.coli and Klebsiella species clinical isolates, including bla CTX-M genotypes in antibiotic-susceptible strains from a Malaysian hospital. The ESBL encoding genotypes such as bla CTX-M presented substantially beyond one-third of the ESBL phenotype-negative or 3GC susceptible E.coli and K.pneumoniae isolated from bloodstream infection. Although clinical outcomes were not worsened with bla CTX-M genotype-positive but ESBL phenotype-negative isolates in bacteremia, the potential implications for AMR spread deserve further investigation.

  11. Jamaluddin NAH, Periyasamy P, Lau CL, Ponnampalavanar S, Lai PSM, Ramli R, et al.
    Antibiotics (Basel), 2021 May 04;10(5).
    PMID: 34064457 DOI: 10.3390/antibiotics10050531
    Antimicrobial resistance remains a significant public health issue, and to a greater extent, caused by the misuse of antimicrobials. Monitoring and benchmarking antimicrobial use is critical for the antimicrobial stewardship team to enhance prudent use of antimicrobial and curb antimicrobial resistance in healthcare settings. Employing a comprehensive and established tool, this study investigated the trends and compliance of antimicrobial prescribing in a tertiary care teaching hospital in Malaysia to identify potential target areas for quality improvement. A point prevalence survey method following the National Antimicrobial Prescribing Survey (NAPS) was used to collect detailed data on antimicrobial prescribing and assessed a set of quality indicators associated with antimicrobial use. The paper-based survey was conducted across 37 adult wards, which included all adult in-patients on the day of the survey to form the study population. Of 478 patients surveyed, 234 (49%) patients received at least one antimicrobial agent, with 357 antimicrobial prescriptions. The highest prevalence of antimicrobial use was within the ICU (80%). Agents used were mainly amoxicillin/β-lactamase inhibitor (14.8%), piperacillin/β-lactamase inhibitor (10.6%) and third-generation cephalosporin (ceftriaxone, 9.5%). Intravenous administration was ordered in 62.7% of prescriptions. Many antimicrobials were prescribed empirically (65.5%) and commonly prescribed for pneumonia (19.6%). The indications for antimicrobials were documented in the patients' notes for 80% of the prescriptions; however, the rate of review/stop date recorded must be improved (33.3%). One-half of surgical antimicrobial prophylaxis was administered for more than 24 h. From 280 assessable prescriptions, 141 (50.4%) were compliant with guidelines. Treating specialties, administration route, class of antimicrobial, and the number of prescriptions per patient were contributing factors associated with compliance. On multivariate analysis, administering non-oral routes of antimicrobial administration, and single antimicrobial prescription prescribed per patient was independently associated with non-compliance. NAPS can produce robust baseline information and identifying targets for improvement in antimicrobial prescribing in reference to current AMS initiatives within the tertiary care teaching hospital. The findings underscore the necessity to expand the AMS efforts towards reinforcing compliance, documentation, improving surgical prophylaxis prescribing practices, and updating local antibiotic guidelines.
  12. Jamaluddin NAH, Periyasamy P, Lau CL, Ponnampalavanar S, Lai PSM, Loong LS, et al.
    Front Pharmacol, 2024;15:1381843.
    PMID: 38720771 DOI: 10.3389/fphar.2024.1381843
    Objectives: This study sought to investigate the quality of antimicrobial prescribing among adult surgical inpatients besides exploring the determinants of non-compliance and inappropriate prescribing to inform stewardship activities. Methods: A cross-sectional point prevalence study employing Hospital National Antimicrobial Prescribing Survey (Hospital NAPS) was conducted in April 2019 at two teaching hospitals in Malaysia. Results: Among 566 surgical inpatients, 44.2% were receiving at least one antimicrobial, for a total of 339 prescriptions. Antimicrobials belonging to the World Health Organization's Watch group were observed in 57.8% of cases. Both hospitals exhibited similar types of antimicrobial treatments prescribed and administration routes. A significant difference in antimicrobial choice was observed between hospitals (p < 0.001). Hospital with electronic prescribing demonstrated better documentation practice (p < 0.001). Guidelines compliance, 32.8% (p = 0.952) and appropriateness, 55.2% (p = 0.561) did not significantly differ. The major contributors of inappropriateness were incorrect duration, (15%) and unnecessary broad-spectrum coverage, (15.6%). Non-compliance and inappropriate prescribing were found to be 2 to 4 times significantly higher with antimicrobial prophylaxis prescription compared to empirical therapy. Conclusion: Antimicrobial stewardship efforts to improve appropriate surgical prescribing are essential. These initiatives should prioritize surgical prophylaxis prescribing, focusing on reducing unnecessarily prolonged use and broad-spectrum antimicrobials, raising awareness among prescribers and promoting proper documentation.
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