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  1. Lee ML, Hassali MA, Shafie AA
    Res Social Adm Pharm, 2013 Jul-Aug;9(4):405-18.
    PMID: 22835711 DOI: 10.1016/j.sapharm.2012.05.010
    BACKGROUND: Treatment default among the smokers hinders the effectiveness of the delivery of cessation services. While many studies have predicted the defaulters' characteristics, the reasons why these smokers dropped out and continued smoking are seldom explored.
    OBJECTIVES: This study examined the barriers encountered by such smokers and their respective health care providers (HCPs) in relation to the discontinuation of cessation treatment.
    METHODS: From May 2010 to March 2011, 15 current adult smokers and 9 HCPs from 2 Quit Smoking Clinics (QSCs) in the Melaka Tengah District, Malacca, Malaysia were interviewed on smoking, cessation, and the QSC. Interviews were audio recorded and transcribed verbatim. The transcripts were subsequently translated into English and analyzed using thematic analysis.
    RESULTS: The barriers encountered were categorized as Individual- and Clinic-level. Both smokers and HCPs acknowledged that the smokers' low intrinsic motivation was the individual-level barrier. The clinic-level barriers were the mismatched perceptions of smokers and HCPs regarding the HCPs' roles, skills, and attitudes, as well as the availability and efficacy of smoking cessation aids (SCAs). While the smokers viewed the program as not helpful, the HCPs cited the lack of organizational support as their main barrier.
    CONCLUSIONS: The reasons for treatment default centered on the overall dissatisfaction with the treatment (due to the program, HCP, and SCA factors) combined with the smokers' low intrinsic motivation. Optimizing the interplay of the extrinsic motivational cues, such as the HCP and SCA factors, would complement the smoker's low intrinsic motivation and thus encourage treatment retention. However, it is necessary to strike a balance between the individual smoker's needs and the availability of organizational support.
    KEYWORDS: Qualitative; Smoking cessation; Treatment discontinuation
    Study site: Quite smoking clinics, Klinik Kesihatan Ayer Keroh, Hospital Melaka, Melaka, Malaysia
  2. Lai NM, Teng CL, Lee ML
    BMC Med, 2011;9:30.
    PMID: 21450083 DOI: 10.1186/1741-7015-9-30
    BACKGROUND: Independent evaluation of clinical evidence is advocated in evidence-based medicine (EBM). However, authors' conclusions are often appealing for readers who look for quick messages. We assessed how well a group of Malaysian hospital practitioners and medical students derived their own conclusions from systematic reviews (SRs) and to what extent these were influenced by their prior beliefs and the direction of the study results.
    METHODS: We conducted two cross-sectional studies: one with hospital practitioners (n = 150) attending an EBM course in June 2008 in a tertiary hospital and one with final-year medical students (n = 35) in November 2008. We showed our participants four Cochrane SR abstracts without the authors' conclusions. For each article, the participants chose a conclusion from among six options comprising different combinations of the direction of effect and the strength of the evidence. We predetermined the single option that best reflected the actual authors' conclusions and labelled this as our best conclusion. We compared the participants' choices with our predetermined best conclusions. Two chosen reviews demonstrated that the intervention was beneficial ("positive"), and two others did not ("negative"). We also asked the participants their prior beliefs about the intervention.
    RESULTS: Overall, 60.3% correctly identified the direction of effect, and 30.1% chose the best conclusions, having identified both the direction of effect and the strength of evidence. More students (48.2%) than practitioners (22.2%) chose the best conclusions (P < 0.001). Fewer than one-half (47%) correctly identified the direction of effect against their prior beliefs. "Positive" SRs were more likely than "negative" SRs to change the participants' beliefs about the effect of the intervention (relative risk (RR) 1.8, 95% confidence interval 1.3 to 2.6) and "convert" those who were previously unsure by making them choose the appropriate direction of effect (RR 1.9, 95% confidence interval 1.3 to 2.8).
    CONCLUSIONS: The majority of our participants could not generate appropriate conclusions from SRs independently. Judicious direction from the authors' conclusions still appears crucial to guiding our health care practitioners in identifying appropriate messages from research. Authors, editors and reviewers should ensure that the conclusions of a paper accurately reflect the results. Similar studies should be conducted in other settings where awareness and application of EBM are different.
  3. Lai NM, Teng CL, Lee ML
    BMC Res Notes, 2010;3:279.
    PMID: 21050429 DOI: 10.1186/1756-0500-3-279
    Despite a recent increase in activities to promote evidence-based practice (EBP), it was unclear how Malaysian hospital practitioners received this new approach in medicine. This study examines their confidence and perceptions on EBP.
  4. Lee ML, Prepageran N, Subha ST
    Med J Malaysia, 2004 Oct;59(4):550-1.
    PMID: 15779594 MyJurnal
    Dentigerous cyst in maxillary sinus, especially in children, is uncommon in Malaysia. Few cases of dentigerous cyst in maxillary sinus in children have been reported in the medical literature. According to Tay AB et al, dentigerous cyst was accounted for 2.3% of the 20 most common diagnosed oral tumors in Singapore form year 1993--1997. This report illustrates a case of the dentigerous cyst in the maxillary sinus, resulting in significant facial swelling, which was managed by endoscopic marsupialization of the cyst.
  5. Fung SY, Lee ML, Tan NH
    Toxicon, 2015 Mar;96:38-45.
    PMID: 25615711 DOI: 10.1016/j.toxicon.2015.01.012
    Snake venom LAAOs have been reported to exhibit a wide range of pharmacological activities, including cytotoxic, edema-inducing, platelet aggregation-inducing/platelet aggregation-inhibiting, bactericidal and antiviral activities. A heat-stable form of l-amino acid oxidase isolated from king cobra (Ophiophagus hannah) venom (OH-LAAO) has been shown to exhibit very potent cytotoxicity against human tumorigenic cells but not in their non-tumorigenic counterparts, and the cytotoxicity was due to the apoptosis-inducing effect of the enzyme. In this work, the molecular mechanism of cell death induced by OH-LAAO was investigated. The enzyme exerts its apoptosis-inducing effect presumably via both intrinsic and extrinsic pathways as suggested by the increase in caspase-8 and -9 activities. Oligonucleotide microarray analysis showed that the expression of a total of 178 genes was significantly altered as a result of oxidative stress induced by the hydrogen peroxide generated by the enzyme. Of the 178 genes, at least 27 genes are involved in apoptosis and cell death. These alterations of gene expression was presumably caused by the direct cytotoxic effect of H2O2 generated during the enzymatic reaction, as well as the non-specific oxidative modifications of signaling molecules that eventually lead to apoptosis and cell death. The very substantial up-regulation of cytochrome P450 genes may also contribute to the potent cytotoxic action of OH-LAAO by producing excessive reactive oxygen species (ROS). In conclusion, the potent apoptosis inducing activity of OH-LAAO was likely due to the direct cytotoxic effect of H2O2 generated during the enzymatic reaction, as well as the non-specific oxidation of signalling molecules.
  6. Lee ML, Tan NH, Fung SY, Sekaran SD
    PMID: 21059402 DOI: 10.1016/j.cbpc.2010.11.001
    The major l-amino acid oxidase (LAAO, EC 1.4.3.2) of king cobra (Ophiophagus hannah) venom is known to be an unusual form of snake venom LAAO as it possesses unique structural features and unusual thermal stability. The antibacterial effects of king cobra venom LAAO were tested against several strains of clinical isolates including Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli using broth microdilution assay. For comparison, the antibacterial effects of several antibiotics (cefotaxime, kanamycin, tetracycline, vancomycin and penicillin) were also examined using the same conditions. King cobra venom LAAO was very effective in inhibiting the two Gram-positive bacteria (S. aureus and S. epidermidis) tested, with minimum inhibitory concentration (MIC) of 0.78μg/mL (0.006μM) and 1.56μg/mL (0.012μM) against S. aureus and S. epidermidis, respectively. The MICs are comparable to the MICs of the antibiotics tested, on a weight basis. However, the LAAO was only moderately effective against three Gram-negative bacteria tested (P. aeruginosa, K. pneumoniae and E. coli), with MIC ranges from 25 to 50μg/mL (0.2-0.4μM). Catalase at the concentration of 1mg/mL abolished the antibacterial effect of LAAO, indicating that the antibacterial effect of the enzyme involves generation of hydrogen peroxide. Binding studies indicated that king cobra venom LAAO binds strongly to the Gram-positive S. aureus and S. epidermidis, but less strongly to the Gram-negative E. coli and P. aeruginosa, indicating that specific binding to bacteria is important for the potent antibacterial activity of the enzyme.
  7. Zhao J, Xiao J, Lee ML, Ma Y
    Springerplus, 2016;5(1):1633.
    PMID: 27722051
    Slopes are subjected to stress redistributions during underground mining activities, and this may eventually cause deformation or landslide. This paper takes Madaling landslide in Guizhou Province, China as a case study to investigate the failure mechanism and its run-out behaviours by using discrete element method. Previous qualitative analysis indicated that the slope experienced four stages of failure mechanisms: (1) development of tension cracks, (2) development of stepped-like creep cracks, (3) development of potential rupture surfaces, and (4) occurrence of the landslide. PFC2D program was employed to model the pre-failure deformation characteristics in order to verify the failure mechanisms quantitatively. Subsequently, the run-out behaviours of the landslide were analyzed by PFC3D program. The results indicated that the movement could be summarized into four stages: acceleration stage, constant movement stage, rapid movement stage, and deceleration and deposition stage.
  8. Lee ML, Fung SY, Chung I, Pailoor J, Cheah SH, Tan NH
    Int J Med Sci, 2014;11(6):593-601.
    PMID: 24782648 DOI: 10.7150/ijms.8096
    King cobra (Ophiophagus hannah) venom L-amino acid oxidase (OH-LAAO), a heat stable enzyme, has been shown to exhibit very potent anti-proliferative activity against human breast and lung tumorigenic cells but not in their non-tumorigenic counterparts. We further examine its in vitro and in vivo anti-tumor activity in a human prostate adenocarcinoma (PC-3) model. OH-LAAO demonstrated potent cytotoxicity against PC-3 cells with IC50 of 0.05 µg/mL after 72 h incubation in vitro. It induced apoptosis as evidenced with an increase in caspase-3/7 cleavages and an increase in annexin V-stained cells. To examine its in vivo anti-tumor activity, we treated PC-3 tumor xenograft implanted subcutaneously in immunodeficient NU/NU (nude) mice with 1 µg/g OH-LAAO given intraperitoneally (i.p.). After 8 weeks of treatment, OH-LAAO treated PC-3 tumors were markedly inhibited, when compared to the control group (P <0.05). TUNEL staining analysis on the tumor sections showed a significantly increase of apoptotic cells in the LAAO-treated animals. Histological examinations of the vital organs in these two groups showed no significant differences with normal tissues, indicating no obvious tissue damage. The treatment also did not cause any significant changes on the body weight of the mice during the duration of the study. These observations suggest that OH-LAAO cytotoxic effects may be specific to tumor xenografts and less to normal organs. Given its potent anti-tumor activities shown in vitro as well as in vivo, the king cobra venom LAAO can potentially be developed to treat prostate cancer and other solid tumors.
  9. Thong PL, Wong SW, Abdul Manaf MR, Lee ML, Kanaheswari Y
    Med J Malaysia, 2019 08;74(4):281-287.
    PMID: 31424034
    INTRODUCTION: The average incidence of spina bifida (SB) in Malaysia is 0.43 among 1,000 live births. The burden of the disease and its impact on the overall development and health though tremendously improved, remains significant. Therefore, current patient management strategies must include quality of life (QOL) measures.

    METHODS: This was a prospective, cross-sectional study on spina bifida children aged 5-20 years, attending the paediatric spina bifida clinics of Universiti Kebangsaan Malaysia Medical Centre Kuala Lumpur and Hospital Tuanku Jaanku Seremban. Scores were obtained using the validated disease specific Parkin QOL questionnaire. Univariate and multivariate analysis were used to investigate factors that were determinants for these outcomes. Results were expressed as beta coefficient and 95% confidence intervals (95%CI).

    RESULTS: A total of 54 children and adolescents aged between 5-20 years completed the questionnaires. Presence of neurogenic bowel (p=0.003), neurogenic bladder (p=0.041), shunt (p=0.044), non-ambulators (p=0.007) and being the only child in the family (p=0.037) were associated with lower QOL scores. Multivariate analysis showed presence of neurogenic bowel (β=0.375, 95%CI: 0.00, 0.15) and being the only child in the family (β=0.250, 95%CI: 0.04, 0.17) explained 22.1% of the variance in the QOL mean percentage scores.

    CONCLUSION: Being a single child in the family was the only socio-demographic variable associated with lower QOL scores. Although several clinical factors appeared to contribute significantly to QOL in spina bifida children, the presence of neurogenic bowel had the greatest impact.

  10. Fong CY, Ong FN, Ong LC, Khoo TB, Lee ML
    Spinal Cord, 2020 Sep;58(9):1030-1036.
    PMID: 32060410 DOI: 10.1038/s41393-020-0441-7
    STUDY DESIGN: Cross-sectional study.

    OBJECTIVE: To determine the prevalence and potential risk factors of vitamin D deficiency and insufficiency among Malaysian children with spina bifida.

    SETTING: Four Malaysian tertiary hospitals.

    METHODS: Children with spina bifida were assessed for potential demographic, disease severity and lifestyle risk factors for vitamin D deficiency and insufficiency. Blood for 25-hydroxy vitamin D (25(OH)D) was taken. Vitamin D deficiency was defined as 25(OH)D levels ≤ 37.5 nmol/L and insufficiency as 37.6-50 nmol/L.

    RESULTS: Eighty children aged 2-18 years (42 males) participated in the study. Vitamin D levels ranged from 14 to 105 nmol/L (mean 52.8, SD 19.1). Vitamin D deficiency was identified in 18 (22.5%) and insufficiency in 26 (32.5%) children. Logistic regression analysis showed that skin exposure to sunlight ≤ 21% body surface area (OR: 6.2, CI 1.7-22.9) and duration of sun exposure ≤ 35 min/day (OR: 4.0, CI 1.2-14.1) were significant risk factors for vitamin D deficiency and insufficiency, respectively.

    CONCLUSIONS: Over half (55%) of Malaysian children with spina bifida seen in urban tertiary hospitals have vitamin D insufficiency and deficiency. Lifestyle sun exposure behaviours were risk factors for vitamin D deficiency and insufficiency.

  11. Lee ML, Tan NH, Fung SY, Tan CS, Ng ST
    PMID: 22454675 DOI: 10.1155/2012/697603
    Lignosus rhinocerus, the tiger milk mushroom, is one of the most important medicinal mushrooms used by the indigenous people of Southeast Asia and China. It has been used to treat breast cancer. A cold water extract (LR-CW) prepared from the sclerotia of L. rhinocerus cultivar was found to exhibit antiproliferative activity against human breast carcinoma (MCF-7) and human lung carcinoma (A549), with IC(50) of 96.7 μg/mL and 466.7 μg/mL, respectively. In comparison, LR-CW did not show significant cytotoxicity against the two corresponding human normal cells, 184B5 (human breast cell) and NL 20 (human lung cell). DNA fragmentation studies suggested that the cytotoxic action of LR-CW against cancer cells is mediated by apoptosis. Sephadex G-50 gel filtration fractionation of LR-CW yielded a high-molecular-weight and a low-molecular-weight fraction. The high-molecular-weight fraction contains mainly carbohydrate (68.7%) and small amount of protein (3.6%), whereas the low-molecular-weight fraction contains 31% carbohydrate and was devoid of protein. Only the high-molecular-weight fraction exhibited antiproliferative activity against cancer cells, with IC(50) of 70.0 μg/mL and 76.7 μg/mL, respectively. Thus, the cytotoxic action of the LR-CW is due to the high-molecular-weight fraction, either the proteins or protein-carbohydrate complex.
  12. Ng DC, Tan KK, Chin L, Ali MM, Lee ML, Mahmood FM, et al.
    Int J Infect Dis, 2021 Jul;108:347-352.
    PMID: 34087485 DOI: 10.1016/j.ijid.2021.05.073
    OBJECTIVES: To describe the clinical and epidemiological characteristics of children with coronavirus disease 2019 (COVID-19) in the state of Negeri Sembilan, Malaysia in the setting of mandatory hospital isolation and quarantine for all confirmed cases.

    METHODS: A multi-centre, retrospective observational study was performed among children aged ≤12 years with laboratory-proven COVID-19 between 1 February and 31 December 2020.

    RESULTS: In total, 261 children (48.7% males, 51.3% females) were included in this study. The median age was 6 years [interquartile range (IQR) 3-10 years]. One hundred and fifty-one children (57.9%) were asymptomatic on presentation. Among the symptomatic cases, fever was the most common presenting symptom. Two hundred and forty-one (92.3%) cases were close contacts of infected household or extended family members. Twenty-one (8.4%) cases had abnormal radiological findings. All cases were discharged alive without requiring supplemental oxygen therapy or any specific treatment during hospitalization. The median duration of hospitalization was 7 days (IQR 6-10 days). One (2.1%) of the uninfected guardians accompanying a child in quarantine tested positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) upon discharge.

    CONCLUSIONS: COVID-19 in children was associated with mild symptoms and a good prognosis. Familial clustering was an important epidemiologic feature in the outbreak in Negeri Sembilan. The risk of transmission of SARS-CoV-2 from children to guardians in hospital isolation was minimal despite close proximity.

  13. Cheung CY, Tay WT, Mitchell P, Wang JJ, Hsu W, Lee ML, et al.
    J Hypertens, 2011 Jul;29(7):1380-91.
    PMID: 21558958 DOI: 10.1097/HJH.0b013e328347266c
    The present study examined the effects of blood pressure on a spectrum of quantitative and qualitative retinal microvascular signs.
  14. Ch'ng CC, Ong LM, Beh KKM, Md Yusuf WS, Chew TF, Lee ML, et al.
    Nephrology (Carlton), 2020 Aug;25(8):644-651.
    PMID: 31900988 DOI: 10.1111/nep.13689
    AIM: Many patients, especially the elderly, who require renal replacement therapies (RRT) have delayed or rejected dialysis for various reasons. Current dialysis guidelines may not be relevant for the elderly or frail patients. We aim to determine survival advantage of initiating dialysis in patients deemed to require RRT.

    METHODS: This was an observational cohort on incident end-stage kidney disease (ESKD) patients from January 1, 2007 to December 31, 2008. The primary outcome was all-cause mortality. Patients contributed person-time from the date of ESKD diagnosis until death, transplant or end of study on December 31, 2014, whichever occurred first. An extended Cox regression model with time-varying exposure to dialysis was used to account for immortal time bias.

    RESULTS: Of 3990 incident ESKD patients included, 70.2% patients initiated dialysis; 78.8% with haemodialysis (HD) while the remaining 21.2% with peritoneal dialysis (PD). Dialysis reduced hazard of death in both elderly and non-elderly patients even after controlling for comorbidities (hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.50, 0.68 and HR 0.76, 95% CI 0.69, 0.85, respectively). HD was protective in both the elderly and non-elderly (HR 0.53, 95% CI 0.45, 0.63 and HR 0.71, 95% CI 0.64, 0.80, respectively). PD significantly reduced risk of death compared to no dialysis in the elderly but not in the non-elderly.

    CONCLUSION: Dialysis improved survival in all incident ESKD patients. The findings suggested a larger protection offered by HD. Although improvement in survival from initiating dialysis was large, its true benefit should take overall quality of life into account. SUMMARY AT A GLANCE This observational study showed that initiation of dialysis improves the survival of end-stage kidney disease (ESKD) patients of all age groups, but the quality of life is an important aspect that has not been explored.

  15. Ng DC, Tan KK, Chin L, Cheng XL, Vijayakulasingam T, Liew DWX, et al.
    PMID: 34723402 DOI: 10.1111/jpc.15821
    AIM: Households are a significant venue for the transmission of SARS-CoV-2. We conducted a study to characterise the transmission dynamics and identify risk factors for household transmission of SARS-CoV-2 in Negeri Sembilan, Malaysia.

    METHODS: This retrospective observational study included 185 families of paediatric COVID-19 cases from 1 February 2020 to 31 December 2020. We identified the index case for each household and gathered the socio-demographic, epidemiological investigation results and risk factors for household transmission from medical case records. The secondary attack rate was calculated, and logistic regression analyses were used to identify risk factors associated with secondary household transmission of SARS-CoV-2.

    RESULTS: Of the 848 household contacts, 466 acquired secondary infections, resulting in a secondary attack rate of 55%. The median age of the secondary cases was 12 years. Female household contacts and household contacts who slept in the same room with the index case were significantly associated with increased risk for COVID-19. Other independent risk factors associated with higher transmission risk in the household included an index case who was symptomatic, a household index case aged greater than 18 years and a male household index case.

    CONCLUSIONS: High rates of household transmission of COVID-19 were found, indicating households were a major setting of transmission of SARS-CoV-2. Our data provide insight into the risk factors for household transmission of SARS-CoV-2 in Malaysia.

  16. David NCE, Juliana H, Chok M, Gan YZ, Tan YC, Nur Adlina MN, et al.
    Med J Malaysia, 2023 Jan;78(1):80-86.
    PMID: 36715196
    INTRODUCTION: The COVID-19 pandemic has reached a phase where many have been infected at least once. Healthcare workers were not spared from being infected. This study aimed to determine the period prevalence of COVID-19 among the paediatric healthcare workers in Negeri Sembilan as the country transitioned into an endemic phase of the pandemic. Additionally, we investigate potential sociodemographic and occupational characteristics associated with SARS-CoV-2 infection among healthcare workers.

    MATERIALS AND METHODS: A cross-sectional study was conducted among the healthcare workers in the paediatric department at three public specialist hospitals in Negeri Sembilan between 15 and 21 April 2022. Data were collected through a self-administered questionnaire.

    RESULTS: Out of the 504 eligible healthcare workers, 493 participated in this study (response rate 97.8%). The overall prevalence of COVID-19 (11 March 2020-15 April 2022) among healthcare workers was 50.9%. The majority (80.1%) were infected during the Omicron wave two months before the survey. Household contacts accounted for 35.9% of infection sources. The proportion of non-doctors in the COVID-19-infected group was significantly higher compared to the non-infected group (74.1% vs 64.0%, p=0.016). The COVID-19-infected group had a higher proportion of schoolgoing children (44.6% vs 30.6%, p=0.001) and children who attended pre-school/sent to the babysitter (49.0% vs 24.4%, p<0.001). There were no significant differences between infection rates among the healthcare workers working in the tertiary hospital and the district hospitals. There were also no significant differences in the proportion of COVID-19- infected doctors and nurses when analysed by seniority.

    CONCLUSION: Our study provided an estimate on the prevalence of COVID-19 among paediatric healthcare workers in Negeri Sembilan and the factors associated with infection, which captures the extent and magnitude of this pandemic on the state's paediatric department. Most infections resulted from household contact, with a higher proportion of infected healthcare workers having young children.

  17. Lu L, Yap YC, Nguyen DQ, Chan YH, Ng JL, Zhang YC, et al.
    Clin Genet, 2022 Jan 22.
    PMID: 35064937 DOI: 10.1111/cge.14116
    Multinational studies have reported monogenic etiologies in 25%-30% of children with steroid-resistant nephrotic syndrome. Such large studies are lacking in Asia. We established Deciphering Diversities: Renal Asian Genetics Network (DRAGoN) and aimed to describe the genetic and clinical spectrums in Asians. We prospectively studied a cohort of 183 probands with suspected genetic glomerulopathies from South and Southeast Asia, of whom 17% had positive family history. Using multi-gene panel sequencing, we detected pathogenic variants in 26 (14%) probands, of whom one-third had COL4A4 or COL4A5 variants (n = 9, 5%). Of those with COL4A5 defects, only 25% had features suggestive of Alport syndrome. Besides traditional predictors for genetic disease (positive family history and extrarenal malformations), we identified novel predictors, namely older age (6.2 vs. 2.4 years; p = 0.001), hematuria (OR 5.6; 95% CI 2.1-14.8; p 60% when a second risk factor (positive family history or extrarenal manifestation) co-existed. The genetic spectrum of glomerulopathies appears different in Asia. Collagen IV genes may be included in sequencing panels even when suggestive clinical features are absent.
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