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  1. Phan CL, Tan SN, Tan SM, Kadir SSSA, Ramli NLM, Lim TO, et al.
    Cancer Genet, 2021 01;250-251:20-24.
    PMID: 33220656 DOI: 10.1016/j.cancergen.2020.11.003
    Acute lymphoblastic leukemia (ALL) cases with e13a3 fusion transcripts are extremely rare. We report a 24-year-old male with Ph-positive (Ph+) ALL with an aberrant e13a3 fusion transcript treated with CD19-specific chimeric antigen receptor T-cell (CAR-T) therapy. He developed refractory disease post-chemotherapy induction, andreceived allogeneic hematopoietic stem cell transplantation (allo-HSCT) after salvage with imatinib in combination with chemotherapy regimen. Unfortunately, the patient relapsed after +90 days post-transplant. He was consented to CAR-T therapy trial and achieved complete remission, highlighting the efficacy of CAR-T treatment in relapsed-refractory B-ALL irrespective of the underlying genetic drivers in leukemia cells .
  2. Noordin A, Sapri HF, Mohamad Sani NA, Leong SK, Tan XE, Tan TL, et al.
    J Med Microbiol, 2016 Dec;65(12):1476-1481.
    PMID: 27902380 DOI: 10.1099/jmm.0.000387
    The annual prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in Malaysia has been estimated to be 30 % to 40 % of all S. aureus infections. Nevertheless, data on the antimicrobial resistance and genetic diversity of Malaysian MRSAs remain few. In 2009, we collected 318 MRSA strains from various wards of our teaching hospital located in Kuala Lumpur, the capital city of Malaysia, and performed antimicrobial susceptibility testing on these strains. The strains were then molecularly characterized via staphylococcal cassette chromosome (SCC) mec and virulence gene (cna, sea, seb, sec, sed, see, seg, seh, sei, eta, etb, Panton-Valentine leukocidin and toxic shock syndrome toxin-1) typing; a subset of 49 strains isolated from the intensive care unit was also typed using PFGE. Most strains were found to be resistant to ciprofloxacin (92.5 %), erythromycin (93.4 %) and gentamicin (86.8 %). The majority (72.0 %) of strains were found to harbour SCCmec type III-SCCmercury with the presence of ccrC, and carried the sea+cna gene combination (49.3 %), with cna as the most prevalent virulence gene (94.0 %) detected. We identified four PFGE clusters, with pulsotype C (n=19) as the dominant example in the intensive care unit, where this pulsotype was found to be associated with carriage of SCCmec type III and the sea gene (P=0.05 and P=0.02, respectively). In summary, the dominant MRSA circulating in our hospital in 2009 was a clone that was ciprofloxacin, erythromycin and gentamicin resistant, carried SCCmec type III-SCCmercury with ccrC and also harboured the sea+cna virulence genes. This clone also appears to be the dominant MRSA circulating in major hospitals in Kuala Lumpur.
  3. Kua CH, Yeo CYY, Tan PC, Char CWT, Tan CWY, Mak V, et al.
    J Am Med Dir Assoc, 2021 01;22(1):82-89.e3.
    PMID: 32423694 DOI: 10.1016/j.jamda.2020.03.012
    OBJECTIVES: Deprescribing has gained awareness recently, but the clinical benefits observed from randomized trials are limited. The aim of this study was to examine the effectiveness of a pharmacist-led 5-step team-care deprescribing intervention in nursing homes to reduce falls (fall risks and fall rates). Secondary aims include reducing mortality, number of hospitalized residents, pill burden, medication cost, and assessing the deprescribing acceptance rate.

    DESIGN: Pragmatic multicenter stepped-wedge cluster randomized controlled trial.

    SETTING AND PARTICIPANTS: Residents across 4 nursing homes in Singapore were included if they were aged 65 years and above, and taking 5 or more medications.

    METHODS: The intervention involved a 5-step deprescribing intervention, which involved a multidisciplinary team-care medication review with pharmacists, physicians, and nurses (in which pharmacists discussed with other team members the feasibility of deprescribing and implementation using the Beers and STOPP criteria) or to an active waitlist control for the first 3 months.

    RESULTS: Two hundred ninety-five residents from 4 nursing homes participated in the study from February 2017 to March 2018. At 6 months, the deprescribing intervention did not reduce falls. Subgroup analysis showed that intervention reduced fall risk scores within the deprescribing-naïve group by 0.18 (P = .04). Intervention was associated with a reduction in mortality [hazard ratio (HR) 0.16, 95% confidence interval 0.07, 0.41; P 

  4. Tan ZN, Wong WK, Nik Zairi Z, Abdullah B, Rahmah N, Zeehaida M, et al.
    Trop Biomed, 2010 Apr;27(1):79-88.
    PMID: 20562817 MyJurnal
    Entamoeba histolytica causes about 50 million infections worldwide with a death rate of over 100,000 annually. In endemic developing countries where resources are limited, microscopic examinations based on Wheatley trichrome staining is commonly used for diagnosis of intestinal amoebiasis. Other than being a time-consuming method, it must be performed promptly after stool collection as trophozoites disintegrate rapidly in faeces. The aim of this study was to compare the efficacies of Eosin-Y, Wheatley trichrome and Iodine stains in delineating the diagnostic features of the parasite, and subsequently to determine the suitable microscopy observation period for detection of erythrophagocytic and non-erythrophagocytic trophozoites spiked in semi-solid stool sample. Wheatley trichrome staining technique was performed using the standard method while the other two techniques were performed on the slides by mixing the respective staining solution with the spiked stool sample. One million of axenically cultured non-erythrophagocytic E. histolytica and erythrophagocytic E. histolytica were separately spiked into 2 g of fresh semisolid faeces. Percentage viability of the trophozoites in the spiked stool sample was determined at 30 minute intervals for eight hours using the 0.4% Trypan blue exclusion method. The results showed that Eosin-Y and Wheatley trichrome stained the karyosome and chromatin granules better as compared to Iodine stain. The percentage viability of non-erythrophagocytic trophozoites decreased faster than the erythrophagocytic form in the first 5 hours and both dropped to ~10% in the 6th hour spiked sample. In conclusion, Eosin-Y staining technique was found to be the easiest to perform, most rapid and as accurate as the commonly used Wheatley trichrome technique; Eosin-Y stained slide sealed with DPX could also be kept as a permanent record. A period not exceeding 6 hours after stool collection was found to be the most suitable in order to obtain good microscopy results of viable trophozoites.
  5. Lee HB, Ginting RT, Tan ST, Tan CH, Alshanableh A, Oleiwi HF, et al.
    Sci Rep, 2016 09 02;6:32645.
    PMID: 27587295 DOI: 10.1038/srep32645
    Anion passivation effect on metal-oxide nano-architecture offers a highly controllable platform for improving charge selectivity and extraction, with direct relevance to their implementation in hybrid solar cells. In current work, we demonstrated the incorporation of fluorine (F) as an anion dopant to address the defect-rich nature of ZnO nanorods (ZNR) and improve the feasibility of its role as electron acceptor. The detailed morphology evolution and defect engineering on ZNR were studied as a function of F-doping concentration (x). Specifically, the rod-shaped arrays of ZnO were transformed into taper-shaped arrays at high x. A hypsochromic shift was observed in optical energy band gap due to the Burstein-Moss effect. A substantial suppression on intrinsic defects in ZnO lattice directly epitomized the novel role of fluorine as an oxygen defect quencher. The results show that 10-FZNR/P3HT device exhibited two-fold higher power conversion efficiency than the pristine ZNR/P3HT device, primarily due to the reduced Schottky defects and charge transfer barrier. Essentially, the reported findings yielded insights on the functions of fluorine on (i) surface -OH passivation, (ii) oxygen vacancies (Vo) occupation and (iii) lattice oxygen substitution, thereby enhancing the photo-physical processes, carrier mobility and concentration of FZNR based device.
  6. Sudarshan VK, Acharya UR, Oh SL, Adam M, Tan JH, Chua CK, et al.
    Comput Biol Med, 2017 04 01;83:48-58.
    PMID: 28231511 DOI: 10.1016/j.compbiomed.2017.01.019
    Identification of alarming features in the electrocardiogram (ECG) signal is extremely significant for the prediction of congestive heart failure (CHF). ECG signal analysis carried out using computer-aided techniques can speed up the diagnosis process and aid in the proper management of CHF patients. Therefore, in this work, dual tree complex wavelets transform (DTCWT)-based methodology is proposed for an automated identification of ECG signals exhibiting CHF from normal. In the experiment, we have performed a DTCWT on ECG segments of 2s duration up to six levels to obtain the coefficients. From these DTCWT coefficients, statistical features are extracted and ranked using Bhattacharyya, entropy, minimum redundancy maximum relevance (mRMR), receiver-operating characteristics (ROC), Wilcoxon, t-test and reliefF methods. Ranked features are subjected to k-nearest neighbor (KNN) and decision tree (DT) classifiers for automated differentiation of CHF and normal ECG signals. We have achieved 99.86% accuracy, 99.78% sensitivity and 99.94% specificity in the identification of CHF affected ECG signals using 45 features. The proposed method is able to detect CHF patients accurately using only 2s of ECG signal length and hence providing sufficient time for the clinicians to further investigate on the severity of CHF and treatments.
  7. Adam M, Oh SL, Sudarshan VK, Koh JE, Hagiwara Y, Tan JH, et al.
    Comput Methods Programs Biomed, 2018 Jul;161:133-143.
    PMID: 29852956 DOI: 10.1016/j.cmpb.2018.04.018
    Cardiovascular diseases (CVDs) are the leading cause of deaths worldwide. The rising mortality rate can be reduced by early detection and treatment interventions. Clinically, electrocardiogram (ECG) signal provides useful information about the cardiac abnormalities and hence employed as a diagnostic modality for the detection of various CVDs. However, subtle changes in these time series indicate a particular disease. Therefore, it may be monotonous, time-consuming and stressful to inspect these ECG beats manually. In order to overcome this limitation of manual ECG signal analysis, this paper uses a novel discrete wavelet transform (DWT) method combined with nonlinear features for automated characterization of CVDs. ECG signals of normal, and dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM) and myocardial infarction (MI) are subjected to five levels of DWT. Relative wavelet of four nonlinear features such as fuzzy entropy, sample entropy, fractal dimension and signal energy are extracted from the DWT coefficients. These features are fed to sequential forward selection (SFS) technique and then ranked using ReliefF method. Our proposed methodology achieved maximum classification accuracy (acc) of 99.27%, sensitivity (sen) of 99.74%, and specificity (spec) of 98.08% with K-nearest neighbor (kNN) classifier using 15 features ranked by the ReliefF method. Our proposed methodology can be used by clinical staff to make faster and accurate diagnosis of CVDs. Thus, the chances of survival can be significantly increased by early detection and treatment of CVDs.
  8. Kwan Z, Bong YB, Tan LL, Lim SX, Yong ASW, Ch'ng CC, et al.
    Arch. Dermatol. Res., 2018 Jul;310(5):443-451.
    PMID: 29687328 DOI: 10.1007/s00403-018-1832-x
    We investigated whether disease severity and clinical manifestations were associated with depression, anxiety, stress and quality of life in adults with psoriasis. Participants were recruited from a dermatology outpatient clinic at a teaching hospital. Information on sociodemographic characteristics, disease severity, presence of arthropathy and head involvement was specifically recorded. Disease severity was assessed using the Psoriasis Area and Severity Index (PASI). Quality of life and psychological symptoms were measured using the Dermatology Life Quality Index (DLQI) and the Depression Anxiety Stress Scale (DASS), respectively. One hundred individuals were recruited. Unadjusted analysis revealed that head involvement was associated with depression [odds ratio (OR) 8.509; 95% confidence interval (CI) 1.077-67.231] and anxiety (OR 6.46; 95% CI 1.401-29.858). Severe disease was associated with a poorer quality of life compared to mild disease (OR 3.750; 95% CI 1.330-10.577). Younger age was associated with an increased risk of depression [mean difference (MD) - 8.640; 95% CI - 16.390 to - 0.890], anxiety (MD - 11.553; 95% CI - 18.478 to- 4.628), stress (MD - 11.440; 95% CI - 19.252 to - 3.628) and severely impaired quality of life (MD - 12.338; 95% CI - 19.548 to - 5.127). Following adjustments for age and disease severity, anxiety, stress and depression remained associated with severely impaired quality of life.
    Study site: Dermatology clinic, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
  9. Tan BK, Tan SB, Chen LC, Chang KM, Chua SS, Balashanker S, et al.
    Patient Prefer Adherence, 2017;11:1027-1034.
    PMID: 28652712 DOI: 10.2147/PPA.S132894
    PURPOSE: Poor adherence to tyrosine kinase inhibitors (TKIs) could compromise the control of chronic myeloid leukemia (CML) and contributes to poorer survival. Little is known about how medication-related issues affect CML patients' adherence to TKI therapy in Malaysia. This qualitative study aimed to explore these issues.

    PATIENTS AND METHODS: Individual face-to-face, semistructured interviews were conducted at the hematology outpatient clinics of two medical centers in Malaysia from August 2015 to January 2016. CML patients aged ≥18 years who were prescribed a TKI were invited to participate in the study. Interviews were audio-recorded, transcribed verbatim, and thematically analyzed.

    RESULTS: Four themes were identified from 18 interviews: 1) concerns about adverse reactions to TKIs, 2) personal beliefs regarding the use of TKIs, 3) mismanagement of TKIs in daily lives, and 4) financial burden in accessing treatment. Participants skipped their TKIs due to ineffective emesis control measures and perceived wastage of medication from vomiting. Participants also modified their TKI therapy due to fear of potential harm from long-term use, and stopped taking their TKIs based on belief in curative claims of traditional medicines and misconception about therapeutic effects of TKIs. Difficulty in integrating the dosing requirements of TKIs into daily lives led to unintentional skipping of doses, as well as the risk of toxicities from inappropriate dosing intervals or food interactions. Furthermore, financial constraints also resulted in delayed initiation of TKIs, missed clinic appointments, and treatment interruptions.

    CONCLUSION: Malaysian CML patients encountered a range of medication-related issues leading to a complex pattern of nonadherence to TKI therapy. Further studies should investigate whether regular contact with patients to improve understanding of treatment rationale, to elicit and address patients' concerns about adverse reactions, and to empower patients with skills to self-manage their medications might promote better adherence to TKIs and improve CML patients' outcome.

    Study site: hematology outpatient clinics of Ampang Hospital (AH) and University Malaya Medical Centre (UMMC) in Malaysia
  10. Kua CH, Yeo CYY, Char CWT, Tan CWY, Tan PC, Mak VS, et al.
    BMJ Open, 2017 05 09;7(5):e015293.
    PMID: 28490560 DOI: 10.1136/bmjopen-2016-015293
    INTRODUCTION: An ageing population has become an urgent concern for Asia in recent times. In nursing homes, polypharmacy has also become a compounding issue. Deprescribing practice is an evidence-based strategy to provide a better outcome in this group of patients; however, its implementation in nursing homes is often challenging, and prospective outcome data on deprescribing practice in the elderly is lacking. Our study assesses the implementation of team-care deprescribing to understand the benefits of this practice in geriatric setting and to explore the factors affecting deprescribing practice.

    METHODS AND ANALYSIS: This multicentre prospective study consists of a prestudy interview questionnaire, and a preintervention and postintervention study to be conducted in the nursing home setting on residents at least 65 years old and on five or more medications. We will employ a cluster randomised stepped-wedge interventional design, based on a five-step (reviewing, checking, discussion, communication and documentation) team-care deprescribing practice coupled with the use of a deprescribing guide (consisting of Beers and STOPP criteria, as well as drug interaction checking), to assess the health and pharmacoeconomic outcome in nursing homes' practice. Primary outcome measures of the intervention will consist of fall risks using a fall risk assessment tool. Other outcomes assessed include fall rates, pill burden including number of pills per day, number of doses per day and number of medications prescribed. Cost-related measures will include the use of cost-benefit analysis, which is calculated from the medication cost savings from deprescribing. For the prestudy interview questionnaire, findings will be analysed qualitatively using thematic analysis.

    ETHICS AND DISSEMINATION: This study is approved by the Domain Specific Review Board of National Healthcare Group, Singapore (2016/00422) and Monash University Human Research Ethics Committee (2016-1430-7791). The study findings shall be disseminated in international conferences and peer-reviewed publications. The study is registered with ClinicalTrials.gov (NCT02863341), Pre-results.

  11. Kwan Z, Bong YB, Tan LL, Lim SX, Yong AS, Ch'ng CC, et al.
    Psychol Health Med, 2017 02;22(2):184-195.
    PMID: 27541601 DOI: 10.1080/13548506.2016.1220603
    Patients with psoriasis may have increased risk of psychological comorbidities. This cross-sectional study aimed at determining associations between sociocultural and socioeconomic factors with the Depression Anxiety Stress Scale (DASS) scores and the Dermatology Life Quality Index (DLQI) scores. Adult patients with psoriasis were recruited from a Dermatology outpatient clinic via convenience sampling. Interviews were conducted regarding socio-demographic factors and willing subjects were requested to complete the DASS and DLQI questionnaires. The Pearson χ2 test, Fisher's exact test and multivariate logistic regression were used for statistical analysis to determine independent predictors of depression, anxiety, stress and severe impairment of quality of life. Unadjusted analysis revealed that depression was associated with Indian ethnicity (p = .041) and severe impairment of quality of life was associated with Indian ethnicity (p = .032), higher education (p = .013), higher income (p = .042), and employment status (p = .014). Multivariate analysis revealed that Indian ethnicity was a predictor of depression (p = .024). For stress, tertiary level of education (p = .020) was an independent risk factor while a higher monthly income was a protective factor (p = .042). The ethnic Indians and Malays were significantly more likely than the ethnic Chinese to suffer reduced quality of life (p = .001 and p = .006 respectively) and subjects with tertiary education were more likely to have severe impairment of quality of life (p = .002). Our study was unique in determining sociocultural influences on psychological complications of psoriasis in a South East Asian population. This has provided invaluable insight into factors predictive of adverse effects of psoriasis on psychological distress and quality of life in our patient population. Future studies should devise interventions to specifically target at risk groups in the development of strategies to reduce morbidity associated with psoriasis.
    Study site: Dermatology clinic, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
  12. Yeo KS, Tan MC, Wong WY, Loh SW, Lam YL, Tan CL, et al.
    Sci Rep, 2016 Sep 27;6:34125.
    PMID: 27671354 DOI: 10.1038/srep34125
    TNF-induced signaling mediates pleiotropic biological consequences including inflammation, immunity, cell proliferation and apoptosis. Misregulation of TNF signaling has been attributed as a major cause of chronic inflammatory diseases and cancer. Jumonji domain-containing protein 8 (JMJD8) belongs to the JmjC family. However, only part of the family members has been described as hydroxylase enzymes that function as histone demethylases. Here, we report that JMJD8 positively regulates TNF-induced NF-κB signaling. Silencing the expression of JMJD8 using RNA interference (RNAi) greatly suppresses TNF-induced expression of several NF-κB-dependent genes. Furthermore, knockdown of JMJD8 expression reduces RIP ubiquitination, IKK kinase activity, delays IκBα degradation and subsequently blocks nuclear translocation of p65. In addition, JMJD8 deficiency enhances TNF-induced apoptosis. Taken together, these findings indicate that JMJD8 functions as a positive regulator of TNF-induced NF-κB signaling.
  13. Wong CH, Tan TR, Heng HY, Ramesh T, Ting PW, Lee WS, et al.
    Med J Malaysia, 2016 Aug;71(4):186-192.
    PMID: 27770117
    Open disclosure is poorly understood in Malaysia but is an ethical and professional responsibility. The objectives of this study were to determine: (1) the perception of parents regarding the severity of medical error in relation to medication use or diagnosis; (2) the preference of parents for information following the medical error and its relation to severity; and (3) the preference of parents with regards to disciplinary action, reporting, and legal action.
  14. Jaafar MH, Mahadeva S, Tan KM, Chin AV, Kamaruzzaman SB, Khor HM, et al.
    Nutr Clin Pract, 2019 Apr;34(2):280-289.
    PMID: 30251336 DOI: 10.1002/ncp.10195
    BACKGROUND: A barrier to gastrostomy feeding exists among Asian clinicians and caregivers due to negative perceptions regarding complications. We compared clinical and nutrition outcomes in older dysphagic Asian patients with nasogastric (NG) or gastrostomy tube feeding using a pragmatic study design.

    METHODS: The choice of enteral tube access was determined by managing clinicians and patients/caregivers. Comparisons of tube feeding methods were made during a 4-month period, adjusting statistically for inherent confounders.

    RESULTS: A total of 102 participants (NG: n = 52, gastrostomy: n = 50) were recruited over 2 years from 2013 to 2015. Subjects on long-term NG tube feeding were older (82.67 ± 7.15 years vs 76.88 ± 7.37 years; P < .001) but both groups had similar clinical indications (stroke: 63.5% NG vs 54% gastrostomy; P = .33). After adjustment for confounders, gastrostomy feeding was associated with fewer tube-related complications (adjusted odds ratio [aOR] = 0.19; 95% confidence interval [CI] = 0.06-0.60) and better complication-free survival rate (aOR = 0.32; 95% CI = 0.12-0.89) at 4-month follow-up. Anthropometric and biochemical nutrition parameters improved significantly in both groups at 4 months, but no significant differences were observed at the end of the study.

    CONCLUSION: Gastrostomy feeding is associated with a greater 4-month complication-free survival and lower tube-related complications compared with long-term NG feeding in older Asians with dysphagia. However, no differences in nutrition outcomes were observed between NG and gastrostomy feeding at 4 months.

  15. Tan YJ, Lee YT, Petersen SH, Kaur G, Kono K, Tan SC, et al.
    Ther Adv Med Oncol, 2019;11:1758835919878977.
    PMID: 31632470 DOI: 10.1177/1758835919878977
    Background: This study aims to investigate the combination effect of a novel sirtuin inhibitor (BZD9L1) with 5-fluorouracil (5-FU) and to determine its molecular mechanism of action in colorectal cancer (CRC).

    Methods: BZD9L1 and 5-FU either as single treatment or in combination were tested against CRC cells to evaluate synergism in cytotoxicity, senescence and formation of micronucleus, cell cycle and apoptosis, as well as the regulation of related molecular players. The effects of combined treatments at different doses on stress and apoptosis, migration, invasion and cell death mechanism were evaluated through two-dimensional and three-dimensional cultures. In vivo studies include investigation on the combination effects of BZD9L1 and 5-FU on colorectal tumour xenograft growth and an evaluation of tumour proliferation and apoptosis using immunohistochemistry.

    Results: Combination treatments exerted synergistic reduction on cell viability on HCT 116 cells but not on HT-29 cells. Combined treatments reduced survival, induced cell cycle arrest, apoptosis, senescence and micronucleation in HCT 116 cells through modulation of multiple responsible molecular players and apoptosis pathways, with no effect in epithelial mesenchymal transition (EMT). Combination treatments regulated SIRT1 and SIRT2 protein expression levels differently and changed SIRT2 protein localization. Combined treatment reduced growth, migration, invasion and viability of HCT 116 spheroids through apoptosis, when compared with the single treatment. In addition, combined treatment was found to reduce tumour growth in vivo through reduction of tumour proliferation and necrosis compared with the vehicle control group. This highlights the potential therapeutic effects of BZD9L1 and 5-FU towards CRC.

    Conclusion: This study may pave the way for use of BZD9L1 as an adjuvant to 5-FU in improving the therapeutic efficacy for the treatment of colorectal cancer.

  16. Kan FK, Tan CC, Von Bahr Greenwood T, Khalid KE, Supramaniam P, Hed Myrberg I, et al.
    Clin Infect Dis, 2020 05 23;70(11):2247-2255.
    PMID: 31188423 DOI: 10.1093/cid/ciz499
    BACKGROUND: Globally, ~500 000 people with severe dengue (SD) require hospitalization yearly; ~12 500 (2.5%) die. Secondary hemophagocytic lymphohistiocytosis (sHLH) is a potentially fatal hyperinflammatory condition for which HLH-directed therapy (as etoposide and dexamethasone) can be life-saving. Prompted by the high mortality in SD and the increasing awareness that patients with SD may develop sHLH, our objectives were to (1) determine the frequency of dengue-HLH in SD, (2) describe clinical features of dengue-HLH, (3) assess mortality rate in SD and dengue-HLH, and (4) identify mortality-associated risk factors in SD.

    METHODS: A 5-year retrospective single-center study in all adult patients with SD admitted to a tertiary intensive care unit in Malaysia.

    RESULTS: Thirty-nine of 180 (22%) patients with SD died. Twenty-one of 180 (12%) had HLH defined as an HLH probability ≥70% according to histo score (HScore); 9 (43%) died. Similarly, 12 of 31 (39%) fulfilling ≥4 and 7 of 9 (78%) fulfilling ≥5 HLH-2004 diagnostic criteria died. Peak values of aspartate aminotransferase (AST), alanine aminotransferase, lactate dehydrogenase, and creatinine correlated to fatality (odds ratios [ORs], 2.9, 3.4, 5.8, and 31.9; all P < .0001), as did peak ferritin (OR, 2.5; P = .0028), nadir platelets (OR, 1.9; P = .00068), hepatomegaly (OR, 2.9; P = .012), and increasing age (OR, 1.2; P = .0043). Multivariable logistic regression revealed peak AST (OR, 2.8; P = .0019), peak creatinine (OR, 7.3; P = .0065), and SOFA (Sequential Organ Failure Assessment) score (OR, 1.4; P = .0051) as independent risk factors of death.

    CONCLUSIONS: Be observant of dengue-HLH due to its high mortality. A prospective study is suggested on prompt HLH-directed therapy in SD patients with hyperinflammation and evolving multiorgan failure at risk of developing dengue-HLH.

  17. Cheong PCH, Yong YS, Fatima A, Ng ST, Tan CS, Kong BH, et al.
    IUBMB Life, 2019 10;71(10):1579-1594.
    PMID: 31190445 DOI: 10.1002/iub.2101
    A lectin gene from the Tiger Milk Mushroom Lignosus rhinocerus TM02® was successfully cloned and expressed via vector pET28a in Escherichia coli BL21(DE3). The recombinant lectin, Rhinocelectin, with a predicted molecular mass of 22.8 kDa, was overexpressed in water-soluble form without signal peptide and purified via native affinity chromatography Ni-NTA agarose. Blast protein analysis indicated the lectin to be homologous to jacalin-related plant lectin. In its native form, Rhinocelectin exists as a homo-tetramer predicted with four chains of identical proteins consisting of 11 beta-sheet structures with only one alpha-helix structure. The antiproliferative activity of the Rhinocelectin against human cancer cell lines was concentration dependent and selective. The IC50 values against triple negative breast cancer cell lines MDA-MB-231 and breast cancer MCF-7 are 36.52 ± 13.55 μg mL-1 and 53.11 ± 22.30 μg mL-1 , respectively. Rhinocelectin is only mildly cytotoxic against the corresponding human nontumorigenic breast cell line 184B5 with IC50 value at 142.19 ± 36.34 μg mL-1 . The IC50 against human lung cancer cell line A549 cells is 46.14 ± 7.42 μg mL-1 while against nontumorigenic lung cell line NL20 is 41.33 ± 7.43 μg mL-1 . The standard anticancer drug, Doxorubicin exhibited IC50 values mostly below 1 μg mL-1 for the cell lines tested. Flow cytometry analysis showed the treated breast cancer cells were arrested at G0/G1 phase and apoptosis induced. Rhinocelectin agglutinated rat and rabbit erythrocytes at a minimal concentration of 3.125 μg mL-1 and 6.250 μg mL-1 , respectively.
  18. Chong SL, Asnawi AWA, Leong TS, Tan JT, Law KB, Hon SL, et al.
    Blood Res, 2021 Sep 30;56(3):175-183.
    PMID: 34462403 DOI: 10.5045/br.2021.2021045
    Background: With the emergence of tyrosine kinase inhibitors and the incorporation of stringent measurable residual disease (MRD) monitoring, risk stratification for BCR-ABL1-positive acute lymphoblastic leukemia (ALL) patients has changed significantly. However, whether this monitoring can replace conventional risk factors in determining whether patients need allogeneic stem cell transplantation is still unclear. This study aimed to determine the impact of BCR-ABL1 monitoring on the outcome of patients with BCR-ABL1-positive ALL after allogeneic stem cell transplantation.

    Methods: We retrospectively analyzed the survival outcome of patients with BCR-ABL1-positive ALL based on the quantification of BCR-ABL1 at 3 timepoints: the end of induction (timepoint 1), post-consolidation week 16 (timepoint 2), and the end of treatment for patients who were either transplant-eligible or non-transplant eligible (timepoint 3).

    Results: From 2006 to 2018, a total of 96 patients newly diagnosed with BCR-ABL1-positive ALL were treated with chemotherapy and tyrosine kinase inhibitors. Thirty-eight (41.3%) patients achieved complete remission, and 33 patients underwent allogeneic stem cell transplantation. Our data showed that pre-transplant MRD monitoring by real-time quantitative polymerase chain reaction had the highest correlation with survival in patients with BCR-ABL1-positive ALL, especially for those who underwent allogeneic stem cell transplantation.

    Conclusion: Patients without MRD pre-transplantation had superior survival compared with those who had MRD, and they had excellent long-term outcomes after allogeneic stem cell transplantation.

  19. Tan RTH, Abdul Rasid SZ, Wan Ismail WK, Tobechan J, Tan ETY, Yusof AN, et al.
    Appl Health Econ Health Policy, 2022 Mar;20(2):255-267.
    PMID: 34927225 DOI: 10.1007/s40258-021-00691-z
    BACKGROUND: The Malaysian public healthcare system is tax funded, with healthcare costs highly subsidized by the Government. The current health financing is not sustainable to cover all the healthcare resources. Introducing a national health insurance (NHI), a prepayment method, would protect the population from financial hardship by reducing out-of-pocket payment, minimizing the barrier to accessing health and achieving equitable healthcare. Studies on the willingness to pay (WTP) for NHI are available in different contexts; however, little was found in Malaysia. In addition, factors affecting the WTP for NHI have been less researched in the Malaysian context.

    OBJECTIVE: This study investigates the WTP for NHI and factors influencing it in Melaka, Malaysia.

    METHOD: Using the contingent valuation method, the researchers distributed a pre-tested self-administered questionnaire to 489 respondents in three leading public hospitals from 1 to 9 November 2019. Multi-stage sampling forms the selection of respondents. Respondents were presented with a hypothetical scenario on NHI and asked whether they would be willing to pay for NHI. Chi-square was used to examine the association between categorical independent variables and WTP for NHI, and binary logistic regression was applied to determine the variables with the most predictive effect towards WTP for NHI.

    RESULTS: Out of 462 usable responses, 344 respondents (74.5%) were willing to pay for NHI. The majority (51.3%) of the respondents were willing to pay 15 Malaysian Ringgit (3.70 US dollars) or more for the NHI scheme. Chi-square analysis revealed that age, marital status, education level, employment status, chronic diseases, and perception towards NHI were significantly associated with WTP for NHI. Binary regression analysis found that marital status and perception towards NHI have the most predictive effect on respondents' WTP for NHI.

    CONCLUSION: This study revealed that the majority of the respondents are willing to pay for NHI if implemented in Malaysia. The findings lay a foundation for implementing a future NHI framework in Malaysia and reference future health financing research.

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