Displaying publications 1 - 20 of 25 in total

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  1. Chao WQ, Azman MZ, Rosdi SA, Tuan-Mustafa T, Tan YJ, Abdullah S, et al.
    Malays Orthop J, 2021 Nov;15(3):84-90.
    PMID: 34966500 DOI: 10.5704/MOJ.2111.013
    Introduction: Distal radial fracture is a commonly encountered fracture. This study aims to study the epidemiology of distal radial fracture and factors affecting the patients' functional outcome one to two years after the injury.

    Materials and methods: This is a retrospective cohort study. The records of patients, fulfilling the radiographical diagnosis of distal radial fracture, and aged 18 and above, who presented to our Emergency Department from 1st January 2018 to 31st December 2018 were retrieved. According to AO classification, we grouped our patients into A (extra-articular), B (partial articular) and C (complete articular). Patients with congenital abnormalities were excluded. Epidemiological data and relevant medical history were obtained and tabulated. A Malaysian language translation of Disability of the Arm, Shoulder and Hand (DASH) questionnaire was used to assess the functional outcome.

    Results: Out of 168 patients' data retrieved, only 110 patients' data were found complete for purposes of this study. The mean DASH score was 13.7 ± 7.87 approximately one to two years post-injury regardless of treatment method. Increasing age was associated with higher DASH score with r=0.407(p<0.001). Several variables had significantly better functional outcome: male gender (p=0.01), Type A fracture configuration (p=0.007) and non-operational treatment (p=0.03). There was no significant difference between treatment modalities in Type A fracture (p=0.094), but Type B (p=0.043) and Type C (p=0.007) had better outcome without surgery. There was no significant difference between different ethnic groups, open or closed fracture and mechanism of injury.

    Conclusion: Better functional outcome after sustaining distal radial fracture was associated with young age, male gender, type A fracture and treated non-operatively. Interestingly, more complex fracture pattern had better functionality were observed without surgery.

  2. Tan YJ, Wendy T, Chieng JY
    Med J Malaysia, 2019 02;74(1):20-24.
    PMID: 30846657
    OBJECTIVE: The aim of this study was to evaluate the demography, and to determine the detection rate of polyps, and detection rate of adenoma at a Malaysian tertiary hospital.

    METHODS: This is a retrospective study of all the patients who had undergone colonoscopy at Gastroenterology endoscopy unit, Serdang Hospital from 1st January 2010 to 31st December 2016. Patients who had a history of colorectal cancer, polyp or inflammatory bowel disease were excluded. Data collected which included patients' demography, indication for colonoscopy, colonoscopy finding, and histopathology results. Data was analysed with SPSS version 16.

    RESULTS: Among the 559 patients who had fulfilled the inclusion criteria (68 males, 44 females), 112 patients were found to have at least one polyp giving the polyp detection rate (PDR) of 20% and 168 polypectomies were performed. The PDR among male patients was higher than that of females (22.5% vs 17.1%, p<0.05). The detection rate of polyp was nearly equal in Malays, Chinese, Indians, and Others. The polyps were more common in those of age 40 years old and above (p<0.05), with the mean age of 63.0±1.5 years. The commonest morphology of polyp in our patients was sessile (58%) and majority was medium size (5-9mm). Otherwise, the polyps were commonly found in the distal colon those that in proximal colon (55.3% vs 38.7%, p<0.05). The adenoma detection rate (ADR) was 19.1% (107/559).

    CONCLUSION: The detection rate of colonic polyp from colonoscopy is 20% in our centre.

  3. Sharma A, Ong JW, Loke MF, Chua EG, Lee JJ, Choi HW, et al.
    Microorganisms, 2021 May 31;9(6).
    PMID: 34073047 DOI: 10.3390/microorganisms9061193
    The ongoing COVID-19 pandemic is a clear and present threat to global public health. Research into how the causative SARS-CoV-2 virus together with its individual constituent genes and proteins interact with target host cells can facilitate the development of improved strategies to manage the acute and long-term complications of COVID-19. In this study, to better understand the biological roles of critical SARS-CoV-2 proteins, we determined and compared the host transcriptomic responses of the HL-CZ human pro-monocytic cell line upon transfection with key viral genes encoding the spike S1 subunit, S2 subunit, nucleocapsid protein (NP), NSP15 (endoribonuclease), and NSP16 (2'-O-ribose-methyltransferase). RNA sequencing followed by gene set enrichment analysis and other bioinformatics tools revealed that host genes associated with topologically incorrect protein, virus receptor activity, heat shock protein binding, endoplasmic reticulum stress, antigen processing and presentation were up-regulated in the presence of viral spike S1 expression. With spike S2 expression, pro-monocytic genes associated with the interferon-gamma-mediated signaling pathway, regulation of phosphatidylinositol 3-kinase activity, adipocytokine signaling pathway, and insulin signaling pathway were down-regulated, whereas those associated with cytokine-mediated signaling were up-regulated. The expression of NSP15 induced the up-regulation of genes associated with neutrophil degranulation, neutrophil-mediated immunity, oxidative phosphorylation, prion disease, and pathways of neurodegeneration. The expression of NSP16 resulted in the down-regulation of genes associated with S-adenosylmethionine-dependent methyltransferase activity. The expression of NP down-regulated genes associated with positive regulation of neurogenesis, nervous system development, and heart development. Taken together, the complex transcriptomic alterations arising from these viral-host gene interactions offer useful insights into host genes and their pathways that potentially contribute to SARS-CoV-2 pathogenesis.
  4. Xu Y, Victorio CBL, Meng T, Jia Q, Tan YJ, Chua KB
    Virol Sin, 2019 Jun;34(3):262-269.
    PMID: 31016480 DOI: 10.1007/s12250-019-00116-1
    Our previous work has shown that Saffold virus (SAFV) induced several rodent and primate cell lines to undergo apoptosis (Xu et al. in Emerg Microb Infect 3:1-8, 2014), but the essential viral proteins of SAFV involved in apoptotic activity lack study. In this study, we individually transfected the viral proteins of SAFV into HEp-2 and Vero cells to assess their ability to induce apoptosis, and found that the 2B and 3C proteins are proapoptotic. Further investigation indicated the transmembrane domain of the 2B protein is essential for the apoptotic activity and tetramer formation of the 2B protein. Our research provides clues for the possible mechanisms of apoptosis induced by SAFV in different cell lines. It also opens up new directions to study viral proteins (the 2B, 3C protein), and sets the stage for future exploration of any possible link between SAFV, inclusive of its related uncultivable genotypes, and multiple sclerosis.
  5. Zhang YZ, Xiong CL, Lin XD, Zhou DJ, Jiang RJ, Xiao QY, et al.
    Infect Genet Evol, 2009 Jan;9(1):87-96.
    PMID: 19041424 DOI: 10.1016/j.meegid.2008.10.014
    There have been three major rabies epidemics in China since the 1950s. To gain more insights into the molecular epidemiology of rabies viruses (RVs) for the third (the current) epidemic, we isolated RV from dogs and humans in major endemic areas, and characterized these isolates genetically by sequencing the entire glycoprotein (G) gene and the G-L non-coding region. These sequences were also compared phylogenetically with RVs isolated in China during previous epidemics and those around the world. Comparison of the entire G genes among the Chinese isolates revealed up to 21.8% divergence at the nucleotide level and 17.8% at the amino acid level. The available Chinese isolates could be divided into two distinct clades, each of which could be further divided into six lineages. Viruses in clade I include most of the Chinese viruses as well as viruses from southeast Asian countries including Indonesia, Malaysia, the Philippines, Thailand, and Vietnam. The viruses in the other clade were found infrequently in China, but are closely related to viruses distributed worldwide among terrestrial animals. Interestingly, most of the viruses isolated during the past 10 years belong to lineage A viruses within clade I whereas most of the viruses isolated before 1996 belong to other lineages within clades I and II. Our results indicated that lineages A viruses have been predominant during the past 10 years and thus are largely responsible for the third and the current epidemic in China. Our results also suggested that the Chinese RV isolates in clade I share a common recent ancestor with those circulating in southeast Asia.
  6. Tan YJ, Ong SC, Kan YM
    Appl Health Econ Health Policy, 2023 Nov;21(6):857-875.
    PMID: 37646915 DOI: 10.1007/s40258-023-00825-5
    OBJECTIVE: This systematic review aimed to summarise the outcomes of economic evaluations that evaluated sodium-glucose cotransporter-2 inhibitors (SGLT2i) in combination with standard of care compared to standard of care alone for patients with chronic heart failure.

    METHODS: This systematic review searched MEDLINE, CINAHL+, Econlit, Scopus, the Cochrane Library, the National Health Service Economic Evaluation Database and the Cost-Effectiveness Analysis Registry from inception to 31 December, 2022, for relevant economic evaluations, which were critically appraised using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) and Bias in Economic Evaluation (ECOBIAS) criteria. The costs, quality-adjusted life-years, incremental cost-effectiveness ratios and cost-effectiveness thresholds were qualitatively analysed. Net monetary benefits at different decision thresholds were also computed. Subgroup analyses addressing the heterogeneity of economic outcomes were conducted. All costs were adjusted to 2023 international dollar (US$) values using the CCEMG-EPPI-Centre cost converter.

    RESULTS: Thirty-nine economic evaluations that evaluated dapagliflozin and empagliflozin in patients with heart failure were found: 32 for the left ventricular ejection fraction (LVEF) ≤ 40% and seven for LVEF > 40%. Sodium-glucose cotransporter-2 inhibitors were cost-effective in all but two economic evaluations for LVEF > 40%. Economic outcomes varied widely, but favoured SGLT2i use in LVEF ≤ 40% over LVEF > 40% and upper-middle income over high-income countries. At a threshold of US$30,000/quality-adjusted life-year, ~ 90% of high to upper-middle income countries would consider SGLT2i cost-effective for heart failure treatment. The generalisability of study findings to low- and low-middle income countries is limited because of insufficient evidence.

    CONCLUSIONS: Using SGLT2i to treat heart failure is cost-effective, with more certainty in LVEF ≤ 40% compared to LVEF > 40%. Policymakers in jurisdictions where economic evaluations are not available could potentially use this study's findings to make informed decisions about treatment adoption.

    SYSTEMATIC REVIEW PROTOCOL REGISTRATION: This study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42023388701).

  7. Lock C, Kwok J, Kumar S, Ahmad-Annuar A, Narayanan V, Ng ASL, et al.
    PMID: 30687707 DOI: 10.3389/fmed.2018.00357
    Normal pressure hydrocephalus (NPH) is a syndrome comprising gait disturbance, cognitive decline and urinary incontinence that is an unique model of reversible brain injury, but it presents as a challenging spectrum of disease cohorts. Diffusion Tensor Imaging (DTI), with its ability to interrogate structural white matter patterns at a microarchitectural level, is a potentially useful tool for the confirmation and characterization of disease cohorts at the clinical-research interface. However, obstacles to its widespread use involve the need for consistent DTI analysis and interpretation tools across collaborator sites. We present the use of DTI profiles, a simplistic methodology to interpret white matter injury patterns based on the morphology of diffusivity parameters. We examined 13 patients with complex NPH, i.e., patients with NPH and overlay from multiple comorbidities, including vascular risk burden and neurodegenerative disease, undergoing extended CSF drainage, clinical assessments, and multi-modal MR imaging. Following appropriate exclusions, we compared the morphology of DTI profiles in such complex NPH patients (n = 12, comprising 4 responders and 8 non-responders) to exemplar DTI profiles from a cohort of classic NPH patients (n = 16) demonstrating responsiveness of white matter injury to ventriculo-peritoneal shunting. In the cohort of complex NPH patients, mean age was 71.3 ± 7.6 years (10 males, 2 females) with a mean MMSE score of 21.1. There were 5 age-matched healthy controls, mean age was 73.4 ± 7.2 years (1 male, 4 females) and mean MMSE score was 26.8. In the exemplar cohort of classic NPH patients, mean age was 74.7 ± 5.9 years (10 males, 6 females) and mean MMSE score was 24.1. There were 9 age-matched healthy controls, mean age was 69.4 ± 9.7 years (4 males, 5 females) and mean MMSE score was 28.6. We found that, despite the challenges of acquiring DTI metrics from differing scanners across collaborator sites and NPH patients presenting as differing cohorts along the spectrum of disease, DTI profiles for responsiveness to interventions were comparable. Distinct DTI characteristics were demonstrated for complex NPH responders vs. non-responders. The morphology of DTI profiles for complex NPH responders mimicked DTI patterns found in predominantly shunt-responsive patients undergoing intervention for classic NPH. However, DTI profiles for complex NPH non-responders was suggestive of atrophy. Our findings suggest that it is possible to use DTI profiles to provide a methodology for rapid description of differing cohorts of disease at the clinical-research interface. By describing DTI measures morphologically, it was possible to consistently compare white matter injury patterns across international collaborator datasets.
  8. Er JL, Goh PN, Lee CY, Tan YJ, Hii LW, Mai CW, et al.
    Apoptosis, 2018 Jun;23(5-6):343-355.
    PMID: 29740790 DOI: 10.1007/s10495-018-1459-6
    Pancreatic adenocarcinoma (PDAC) is a highly aggressive cancer with a high chance of recurrence, limited treatment options, and poor prognosis. A recent study has classified pancreatic cancers into four molecular subtypes: (1) squamous, (2) immunogenic, (3) pancreatic progenitor and (4) aberrantly differentiated endocrine exocrine. Among all the subtypes, the squamous subtype has the worst prognosis. This study aims to utilize large scale genomic datasets and computational systems biology to identify potential drugs targeting the squamous subtype of PDAC through combination therapy. Using the transcriptomic data available from the International Cancer Genome Consortium, Cancer Cell Line Encyclopedia and Connectivity Map, we identified 26 small molecules that could target the squamous subtype of PDAC. Among them include inhibitors targeting the SRC proto-oncogene (SRC) and the mitogen-activated protein kinase kinase 1/2 (MEK1/2). Further analyses demonstrated that the SRC inhibitors (dasatinib and PP2) and MEK1/2 inhibitor (pimasertib) synergized gemcitabine sensitivity specifically in the squamous subtype of PDAC cells (SW1990 and BxPC3), but not in the PDAC progenitor cells (AsPC1). Further analysis revealed that the synergistic effects are dependent on SRC or MEK1/2 activities, as overexpression of SRC or MEK1/2 completely abrogated the synergistic effects SRC inhibitors (dasatinib and PP2) and MEK1/2 inhibitor (pimasertib). In contrast, no significant toxicity was observed in the MRC5 human lung fibroblast and ARPE-19 human retinal pigment epithelial cells. Together, our findings suggest that combinations of SRC or MEK inhibitors with gemcitabine possess synergistic effects on the squamous subtype of PDAC cells and warrant further investigation.
  9. Lim SY, Tan AH, Foo JN, Tan YJ, Chew EG, Annuar AA, et al.
    J Mov Disord, 2024 Jan 31.
    PMID: 38291878 DOI: 10.14802/jmd.24009
    Lysosomal dysfunction plays an important role in neurodegenerative diseases, including Parkinson's disease (PD) and possibly also Parkinson-plus syndromes such as progressive supranuclear palsy (PSP). This is exemplified by the involvement of the GBA1 gene, which results in a deficiency of the lysosomal enzyme glucocerebrosidase, and is currently the most frequently identified genetic factor underlying PD worldwide. Pathogenic variants in the SMPD1 gene are a recessive cause of Niemann-Pick disease type A and B. Here, we provide the first report on an association between a loss-of-function SMPD1 gene variant present in heterozygous state (p.Pro332Arg/p.P332R, which is known to result in reduced lysosomal acid sphingomyelinase activity), with PSP-Richardson syndrome in three unrelated patients of Chinese ancestry.
  10. Lee YT, Tan YJ, Oon CE
    Eur J Pharmacol, 2018 Sep 05;834:188-196.
    PMID: 30031797 DOI: 10.1016/j.ejphar.2018.07.034
    Molecular targeted therapies are revolutionized therapeutics which interfere with specific molecules to block cancer growth, progression, and metastasis. Many molecular targeted therapies approved by the Food and Drug Administration (FDA), have demonstrated remarkable clinical success in the treatment of a myriad of cancer types including breast, leukemia, colorectal, lung, and ovarian cancers. This review provides an update on the different types of molecular targeted therapies used in the treatment of cancer, focusing on the fundamentals of molecular targeted therapy, its mode of action in cancer treatment, as well as its advantages and limitations.
  11. Tan YJ, Lee YT, Yeong KY, Petersen SH, Kono K, Tan SC, et al.
    Future Med Chem, 2018 Sep 01;10(17):2039-2057.
    PMID: 30066578 DOI: 10.4155/fmc-2018-0052
    AIM: This study aims to investigate the mode of action of a novel sirtuin inhibitor (BZD9L1) and its associated molecular pathways in colorectal cancer (CRC) cells.

    MATERIALS & METHODS: BZD9L1 was tested against metastatic CRC cell lines to evaluate cytotoxicity, cell cycle and apoptosis, senescence, apoptosis related genes and protein expressions, as well as effect against major cancer signaling pathways.

    RESULTS & CONCLUSION: BZD9L1 reduced the viability, cell migration and colony forming ability of both HCT 116 and HT-29 metastatic CRC cell lines through apoptosis. BZD9L1 regulated major cancer pathways differently in CRC with different mutation profiles. BZD9L1 exhibited anticancer activities as a cytotoxic drug in CRC and as a promising therapeutic strategy in CRC treatment.

  12. 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.

  13. Tan YJ, Lee YT, Mancera RL, Oon CE
    Life Sci, 2021 Nov 01;284:119747.
    PMID: 34171380 DOI: 10.1016/j.lfs.2021.119747
    BZD9L1 was previously described as a SIRT1/2 inhibitor with anti-cancer activities in colorectal cancer (CRC), either as a standalone chemotherapy or in combination with 5-fluorouracil. BZD9L1 was reported to induce apoptosis in CRC cells; however, the network of intracellular pathways and crosstalk between molecular players mediated by BZD9L1 is not fully understood. This study aimed to uncover the mechanisms involved in BZD9L1-mediated cytotoxicity based on previous and new findings for the prediction and identification of related pathways and key molecular players. BZD9L1-regulated candidate targets (RCTs) were identified using a range of molecular, cell-based and biochemical techniques on the HCT 116 cell line. BZD9L1 regulated major cancer pathways including Notch, p53, cell cycle, NFκB, Myc/MAX, and MAPK/ERK signalling pathways. BZD9L1 also induced reactive oxygen species (ROS), regulated apoptosis-related proteins, and altered cell polarity and adhesion profiles. In silico analyses revealed that most RCTs were interconnected, and were involved in the modulation of catalytic activity, metabolism and transcription regulation, response to cytokines, and apoptosis signalling pathways. These RCTs were implicated in p53-dependent apoptosis pathway. This study provides the first assessment of possible associations of molecular players underlying the cytotoxic activity of BZD9L1, and establishes the links between RCTs and apoptosis through the p53 pathway.
  14. Lee YT, Tan YJ, Oon CE
    Acta Pharm Sin B, 2023 Feb;13(2):478-497.
    PMID: 36873180 DOI: 10.1016/j.apsb.2022.09.010
    Cancer is the second leading cause of mortality globally which remains a continuing threat to human health today. Drug insensitivity and resistance are critical hurdles in cancer treatment; therefore, the development of new entities targeting malignant cells is considered a high priority. Targeted therapy is the cornerstone of precision medicine. The synthesis of benzimidazole has garnered the attention of medicinal chemists and biologists due to its remarkable medicinal and pharmacological properties. Benzimidazole has a heterocyclic pharmacophore, which is an essential scaffold in drug and pharmaceutical development. Multiple studies have demonstrated the bioactivities of benzimidazole and its derivatives as potential anticancer therapeutics, either through targeting specific molecules or non-gene-specific strategies. This review provides an update on the mechanism of actions of various benzimidazole derivatives and the structure‒activity relationship from conventional anticancer to precision healthcare and from bench to clinics.
  15. Lee YT, Tan YJ, Oon CE
    Biomedicines, 2023 Nov 15;11(11).
    PMID: 38002059 DOI: 10.3390/biomedicines11113059
    Growing evidence has highlighted that mitochondrial dysfunction contributes to drug-induced toxicities and leads to drug attrition and post-market withdrawals. The acetylation or deacetylation of mitochondrial proteins can affect mitochondrial functions as the cells adapt to various cellular stresses and other metabolic challenges. SIRTs act as critical deacetylases in modulating mitochondrial function in response to drug toxicity, oxidative stress, reactive oxygen species (ROS), and energy metabolism. We previously showed that a recently characterised SIRT inhibitor (BZD9L1) is non-toxic in rodents in a short-term toxicity evaluation. However, the impact of BZD9L1 on mitochondrial function is unknown. This work aims to determine the effects of BZD9L1 on mitochondrial function in human normal liver and kidney-derived cell lines using the Agilent Seahorse Cell Mito Stress Test to complement our short-term toxicity evaluations in vivo. The Mito Stress assay revealed that BZD9L1 could potentially trigger oxidative stress by inducing ROS, which promotes proton leak and reduces coupling efficiency in liver-derived THLE cells. However, the same was not observed in human kidney-derived HEK293 cells. Interestingly, BZD9L1 had no impact on SIRT3 protein expression in both cell lines but affected SOD2 and its acetylated form at 72 h in THLE cells, indicating that BZD9L1 exerted its effect through SIRT3 activity rather than protein expression. In contrast, BZD9L1 reduced SIRT1 protein expression and impacted the p53 protein differently in both cell lines. Although BZD9L1 did not affect the spare respiratory capacity in vitro, these findings call for further validation of mitochondrial function through assessment of other mitochondrial parameters to evaluate the safety of BZD9L1.
  16. de Vries M, Cader S, Colleer L, Batteux E, Yasdiman MB, Tan YJ, et al.
    J Autism Dev Disord, 2020 Apr;50(4):1281-1294.
    PMID: 31901119 DOI: 10.1007/s10803-019-04343-z
    Cultural background might influence knowledge and attitudes regarding autism, influencing willingness to interact. We studied whether beliefs, knowledge, contact, and attitude differed between the UK and Malaysia. With mediation analyses, we studied how these factors influenced willingness to interact. Autism was more often linked to food in the UK, and to upbringing in Malaysia. Knowledge, contact, and acceptance were greater in the UK. When excluding psychology students, Malaysian students were less willing to interact with autistic people. Knowledge and contact appeared to improve acceptance, but acceptance did not mediate the relation between country, beliefs, knowledge, and experience; and willingness to interact. Knowledge and contact regarding autism might improve acceptance in different cultures, but how acceptance could improve interaction is unclear.
  17. Choo XY, Lim SY, Chinna K, Tan YJ, Yong VW, Lim JL, et al.
    Neurol Sci, 2020 Oct;41(10):2831-2842.
    PMID: 32314118 DOI: 10.1007/s10072-020-04396-4
    INTRODUCTION: Little is known regarding the educational needs and perspectives of people living with Parkinson's disease (PD), particularly in Asia.

    OBJECTIVE: To assess knowledge and perceptions regarding PD in a large multiethnic urban Asian cohort of patients and caregivers.

    METHODS: We conducted a survey at a university hospital neurology clinic, using a novel Knowledge and Perception of Parkinson's Disease Questionnaire (KPPDQ).

    RESULTS: The KPPDQ had satisfactory psychometric properties among patients and caregivers. Five hundred subjects were recruited with a 97% response rate (211 patients, 273 caregivers). Non-motor symptoms such as urinary problems, visual hallucinations and pain were relatively poorly recognized. Many (≈ 50-80%) respondents incorrectly believed that all PD patients experience tremor, that PD is usually familial, and that there is a cure for PD. About one-half perceived PD to be caused by something the patient had done in the past, and that PD medications were likely to cause internal organ damage. Issues of stigma/shame were relevant to one-third of patients, and 70% of patients perceived themselves to be a burden to others. Two-thirds of participants felt that PD imposed a heavy financial toll. Participants were about equally divided as to whether they would consider treatment with deep brain stimulation, tube feeding or invasive ventilation. Over three-quarters of patients expressed a preference to die at home.

    CONCLUSIONS: Important knowledge gaps, misperceptions and perspectives on PD were identified, highlighting the need for further efforts to raise awareness and provide accurate information regarding PD, and to address patient's and caregivers' needs and preferences.

  18. Yong VW, Tan YJ, Ng YD, Choo XY, Sugumaran K, Chinna K, et al.
    Parkinsonism Relat Disord, 2020 08;77:28-35.
    PMID: 32615497 DOI: 10.1016/j.parkreldis.2020.06.015
    INTRODUCTION: Although weight loss is common in Parkinson's disease (PD), longitudinal studies assessing weight and body composition changes are limited.

    METHODS: In this three-year longitudinal study, 125 subjects (77 PD patients and 48 spousal/sibling controls) underwent clinical, biochemical and body composition assessments using dual-energy X-ray absorptiometry.

    RESULTS: Patients were older than controls (65.6 ± 8.9 vs. 62.6 ± 7.1, P = 0.049), with no significant differences in gender, comorbidities, dietary intake and physical activity. Clinically significant weight loss (≥5% from baseline weight) was recorded in 41.6% of patients, with a doubling of cases (6.5 to 13.0%) classified as underweight at study end. Over three years, patients demonstrated greater reductions in BMI (mean -1.2 kg/m2, 95%CI-2.0 to -0.4), whole-body fat percentage (-2.5% points, 95%CI-3.9 to -1.0), fat mass index (FMI) (-0.9 kg/m2, 95%CI-1.4 to -0.4), visceral fat mass (-0.1 kg, 95%CI-0.2 to 0.0), and subcutaneous fat mass (-1.9 kg, 95%CI-3.4 to -0.5) than in controls, with significant group-by-time interactions after adjusting for age and gender. Notably, 31.2% and 53.3% of patients had FMI<3rd (severe fat deficit) and <10th centiles, respectively. Muscle mass indices decreased over time in both groups, without significant group-by-time interactions. Multiple linear regression models showed that loss of body weight and fat mass in patients were associated with age, dyskinesia, psychosis and constipation.

    CONCLUSIONS: We found progressive loss of weight in PD patients, with greater loss of both visceral and subcutaneous fat, but not muscle, compared to controls. Several associated factors (motor and non-motor disease features) were identified for these changes, providing insights on possible mechanisms and therapeutic targets.

  19. Tan YJ, Lim SY, Yong VW, Choo XY, Ng YD, Sugumaran K, et al.
    J Clin Densitom, 2020 07 30;24(3):351-361.
    PMID: 32888777 DOI: 10.1016/j.jocd.2020.07.001
    Osteoporotic fractures are common in Parkinson's disease (PD). Standard dual-energy X-ray absorptiometry (DXA) measuring bone mineral density (BMD) at the femoral neck and lumbar spine (central sites) has suboptimal sensitivity in predicting fracture risk in the general population. An association between sarcopenia and osteoporosis in PD has not been studied. We compared BMD and osteoporosis prevalence in PD patients vs controls; determined the osteoporosis detection rates using central alone vs central plus distal radius DXA; and analyzed factors (in particular, sarcopenia) associated with osteoporosis. One hundred and fifty-six subjects (102 patients with PD, 54 spousal/sibling controls) underwent femoral neck-lumbar spine-distal radius DXA. Seventy-three patients and 46 controls were assessed for sarcopenia using whole-body DXA and handgrip strength. Patients underwent clinical and serum biochemical evaluations. PD patients had significantly lower body mass index compared to controls. After adjustment for possible confounders, distal radius BMD and T-scores were significantly lower in PD patients compared to controls, but not at the femoral neck/lumbar spine. With distal radius DXA, an additional 11.0% of patients were diagnosed with osteoporosis (32.0% to 43.0%), vs 3.7% in controls (33.3% to 37.0%) additionally diagnosed; this increase was largely driven by the markedly higher detection rate in female PD patients. Female gender (adjusted odds ratio [ORadjusted] = 11.3, 95% confidence interval [CI]: 2.6-48.6) and sarcopenia (ORadjusted = 8.4, 95% CI: 1.1-64.9) were independent predictors for osteoporosis in PD. Distal radius DXA increased osteoporosis detection, especially in female PD patients, suggesting that diagnostic protocols for osteoporosis in PD could be optimized. A close association between osteoporosis and sarcopenia was documented for the first time in PD, which has important implications for clinical management and future research.
  20. Oh AL, Tan YJ, Chong WC, Chieng IYY, Chan JYM, Kho BP, et al.
    J Pharm Policy Pract, 2022 Jan 24;15(1):7.
    PMID: 35073999 DOI: 10.1186/s40545-022-00405-3
    BACKGROUND: Delays in producing discharge prescriptions have hindered the provision of bedside dispensing services (BEDISC) that enable medication reconciliation and pharmaceutical intervention, which is an important element in transitional care medication safety. We aimed to assess the impact of early medication discharge planning on the delivery of BEDISC in terms of the rate of bedside dispensing, medication errors, and cost-saving from medication reconciliation by reusing patient's own medicines (POMs).

    METHODS: A pre-post intervention study was conducted at medical wards in a public tertiary hospital. During the intervention phase, a structured bedside dispensing process was delineated and conveyed to the doctors, nurses, and pharmacists. Regular verbal reminders were given to the doctors to prioritize discharge patients by producing the prescriptions once discharge decisions had been made and nurses to hand the prescriptions to ward pharmacists and not patients. Throughout the study, ward pharmacists were involved in medication reconciliation via screening of discharge prescriptions and reusing POMs, performed pharmaceutical interventions for any medication errors detected, and provided bedside dispensing with discharge counseling. Comparisons were made between bedside versus counter-dispensing at pre-post intervention phases using the chi-square test.

    RESULTS: A total of 1097 and 817 discharge prescriptions were dispensed in the pre-intervention and post-intervention phases, respectively. The bedside dispensing rate increased by 13.5% following remedial actions (p 

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