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  1. Ng JSC, Tan YX, Alwi NAA, Yee KM, Rashid AHA, Tan KL, et al.
    J Curr Glaucoma Pract, 2022 2 18;15(3):139-143.
    PMID: 35173396 DOI: 10.5005/jp-journals-10078-1319
    Aim and objective: To evaluate the safety of two new generic ophthalmic formulations, Latanost® (latanoprost) and Latacom® (latanoprost and timolol) by utilizing the three-dimensional reconstructed human cornea-like epithelium (RhCE) tissue constructs as an in vitro model in the assessment of ocular irritation.

    Materials and methods: In vitro irritation test was conducted on Latanost® (LTN) and Latacom® (LTC) and their corresponding innovators, Xalatan® (XLT) and Xalacom® (XLC), respectively, by using RhCE. According to the OECD guidelines No. 492 on the testing of chemicals, the ophthalmic formulations were assessed via topical exposure of the formulations on in vitro RhCE tissue. Cell viability was measured by MTT assay.

    Results: The mean cell viability percentage of LTN and XLT was 70.5 and 75.7%, respectively, whereas, for LTC and XLC, the percentage viability was 95.3 and 85.7%, respectively. The two new generic formulations (LTN and LTC) did not reduce the cell viability of the RhCE tissue to ≤60%. Thus, both can be considered as nonirritant.

    Conclusion: Both newly developed generics are nonocular irritants.

    Clinical significance: This study informs the safety assessment of new generic antiglaucoma ophthalmic solutions applicable for long-term glaucoma treatment. The formulations aim to keep eye irritation to a minimum level.

    How to cite this article: Ng JSC, Tan YX, Alwi NAA, et al. In Vitro Toxicity Evaluation of New Generic Latanost® and Latacom® as an Ophthalmic Formulation. J Curr Glaucoma Pract 2021;15(3):139-143.

  2. Tay KT, Tan XH, Tan LHE, Vythilingam D, Chin AMC, Loh V, et al.
    J Interprof Care, 2020 12 08;35(6):927-939.
    PMID: 33290115 DOI: 10.1080/13561820.2020.1818700
    Interprofessional mentoring in palliative care sees different members of the interprofessional team providing holistic, personalised andlongitudinal mentoring support, skills training and knowledge transfer as they mentor trainees at different points along their mentoring journeys. However, gaps in practice and their risk of potential mentoring malpractice even as interprofessional mentoring use continues to grow in palliative medicine underlines the need for careful scrutiny of its characteristics and constituents in order to enhance the design, evaluation and oversight of interprofessional mentoring programmes. Hence, a systematic scoping review on prevailing accounts of interprofessional mentoring in medicine is conducted to address this gap. Using Arksey and O'Malley's (2005) methodological framework for conducting scoping reviews and identical search strategies, 6 reviewers performed independent literature reviews of accounts of interprofessional mentoring published in 10 databases. Braun and Clarke's (2006) thematic analysis approach was adopted to evaluate across different mentoring settings. A total of 11111 abstracts were identified from 10 databases, 103 full-text articles reviewed and 14 full-text articles were thematically analysed to reveal 4 themes: characterizing, implementing, evaluating and obstacles to interprofessional mentoring. Interprofessional mentoring is founded upon a respectful and collaborative mentoring relationship that thrives despite inevitable differences in individual values, ethical perspectives at different career stages within diverse working environments. This warrants effective mentor-mentee trainings, alignment of expectations, roles and responsibilities, goals and timelines, and effective oversight of the programmes. Drawing upon the data provided, an interprofessional mentoring framework is forwarded to guide the design, evaluation and oversight of the programmes.
  3. 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 

  4. Mat S, Ng CT, Tan PJ, Ramli N, Fadzli F, Rozalli FI, et al.
    PM R, 2018 03;10(3):254-262.
    PMID: 28827207 DOI: 10.1016/j.pmrj.2017.08.405
    BACKGROUND: Osteoarthritis (OA) is considered an established risk factor for falls. Published studies evaluating secondary falls prevention strategies among individuals with OA are limited.
    OBJECTIVE: To evaluate the effect of a personalized home-based exercise program to improve postural balance, fear of falling, and falls risk in older fallers with knee OA and gait and balance problems.
    DESIGN: Randomized controlled trial.
    SETTING: University of Malaya Medical Centre.
    PARTICIPANTS: Fallers who had both radiological OA and a Timed Up and Go (TUG) score of over 13.5 seconds.
    MAIN OUTCOME MEASURE: Postural sway (composite sway) was quantified with the Modified Clinical Test of Sensory Interaction on Balance (mCTSIB) under 4 different sensory conditions: eyes open on firm surface, eyes closed on firm surface, eyes open on unstable foam surface, and eyes closed on unstable foam surface. Participants were asked to stand upright and to attempt to hold their position for 10 seconds for each test condition. The average reading for all conditions were calculated.
    METHODS: Participants randomized to the intervention arm received a home-based modified Otago Exercise Program (OEP) as part of a multifactorial intervention, whereas control participants received general health advice and conventional treatment. This was a secondary subgroup analysis from an original randomized controlled trial, the Malaysian Falls Assessment and Intervention Trial (MyFAIT) (trial registration number: ISRCTN11674947). Posturography using a long force plate balance platform (Balancemaster, NeuroCom, USA), the Knee injury and Osteoarthritis Outcome Score (KOOS) and the short-form Falls Efficacy Scale-International (short FES-I) were assessed at baseline and 6 months.
    RESULTS: Results of 41 fallers with radiological evidence of OA and impaired TUG (intervention, 17; control, 24) were available for the final analysis. Between-group analysis revealed significant improvements in the Modified Clinical Test of Sensory Interaction on Balance (mCTSIB), Limits of Stability (LOS), and short FES-I scores by the intervention group compared to the control group at 6 months. No significant difference in time to first fall or in fall-free survival between the intervention and control groups was found.

    CONCLUSION: Home-based balance and strength exercises benefited older fallers with OA and gait and balance disorders by improving postural control, with no observable trend in reduction of fall recurrence. Our findings will now inform a future, adequately powered, randomized controlled study using fall events as definitive outcomes.

    LEVEL OF EVIDENCE: I.
  5. Maherally Z, Fillmore HL, Tan SL, Tan SF, Jassam SA, Quack FI, et al.
    FASEB J, 2018 01;32(1):168-182.
    PMID: 28883042 DOI: 10.1096/fj.201700162R
    The blood-brain barrier (BBB) consists of endothelial cells, astrocytes, and pericytes embedded in basal lamina (BL). Most in vitro models use nonhuman, monolayer cultures for therapeutic-delivery studies, relying on transendothelial electrical resistance (TEER) measurements without other tight-junction (TJ) formation parameters. We aimed to develop reliable, reproducible, in vitro 3-dimensional (3D) models incorporating relevant human, in vivo cell types and BL proteins. The 3D BBB models were constructed with human brain endothelial cells, human astrocytes, and human brain pericytes in mono-, co-, and tricultures. TEER was measured in 3D models using a volt/ohmmeter and cellZscope. Influence of BL proteins-laminin, fibronectin, collagen type IV, agrin, and perlecan-on adhesion and TEER was assessed using an electric cell-substrate impedance-sensing system. TJ protein expression was assessed by Western blotting (WB) and immunocytochemistry (ICC). Perlecan (10 µg/ml) evoked unreportedly high, in vitro TEER values (1200 Ω) and the strongest adhesion. Coculturing endothelial cells with astrocytes yielded the greatest resistance over time. ICC and WB results correlated with resistance levels, with evidence of prominent occludin expression in cocultures. BL proteins exerted differential effects on TEER, whereas astrocytes in contact yielded higher TEER values and TJ expression.-Maherally, Z., Fillmore, H. L., Tan, S. L., Tan, S. F., Jassam, S. A., Quack, F. I., Hatherell, K. E., Pilkington, G. J. Real-time acquisition of transendothelial electrical resistance in an all-human, in vitro, 3-dimensional, blood-brain barrier model exemplifies tight-junction integrity.
  6. Fong JYM, Tan VJH, Lee JR, Tong ZGM, Foong YK, Tan JME, et al.
    Eur J Dent Educ, 2018 Aug;22(3):160-166.
    PMID: 29266663 DOI: 10.1111/eje.12297
    AIM: To evaluate the effectiveness of clinical audit-feedback cycle as an educational tool in improving the technical quality of root canal therapy (RCT) and compliance with record keeping performed by dental undergraduates.

    METHODS: Clinical audit learning was introduced in Year 3 of a 5-year curriculum for dental undergraduates. During classroom activities, students were briefed on clinical audit, selected their audit topics in groups of 5 or 6 students, and prepared and presented their audit protocols. One chosen topic was RCT, in which 3 different cohorts of Year 3 students conducted retrospective audits of patients' records in 2012, 2014 and 2015 for their compliance with recommended record keeping criteria and their performance in RCT. Students were trained by and calibrated against an endodontist (κ ≥ 0.8). After each audit, the findings were reported in class, and recommendations were made for improvement in performance of RCT and record keeping. Students' compliance with published guidelines was presented and their RCT performances in each year were compared using the chi-square test.

    RESULTS: Overall compliance with of record keeping guidelines was 44.1% in 2012, 79.6% in 2014 and 94.6% in 2015 (P = .001). In the 2012 audit, acceptable extension, condensation and the absence of mishap were observed in 72.4, 75.7% and 91.5%; in the 2014 audit, 95.1%, 64.8% and 51.4%; and in 2015 audit, 96.4%, 82.1% and 92.8% of cases, respectively. In 2015, 76.8% of root canal fillings met all 3 technical quality criteria when compared to 48.6% in 2014 and 44.7% in 2012 (P = .001).

    CONCLUSION: Clinical audit-feedback cycle is an effective educational tool for improving dental undergraduates' compliance with record keeping and performance in the technical quality of RCT.

  7. Tan JH, Hagiwara Y, Pang W, Lim I, Oh SL, Adam M, et al.
    Comput Biol Med, 2018 03 01;94:19-26.
    PMID: 29358103 DOI: 10.1016/j.compbiomed.2017.12.023
    Coronary artery disease (CAD) is the most common cause of heart disease globally. This is because there is no symptom exhibited in its initial phase until the disease progresses to an advanced stage. The electrocardiogram (ECG) is a widely accessible diagnostic tool to diagnose CAD that captures abnormal activity of the heart. However, it lacks diagnostic sensitivity. One reason is that, it is very challenging to visually interpret the ECG signal due to its very low amplitude. Hence, identification of abnormal ECG morphology by clinicians may be prone to error. Thus, it is essential to develop a software which can provide an automated and objective interpretation of the ECG signal. This paper proposes the implementation of long short-term memory (LSTM) network with convolutional neural network (CNN) to automatically diagnose CAD ECG signals accurately. Our proposed deep learning model is able to detect CAD ECG signals with a diagnostic accuracy of 99.85% with blindfold strategy. The developed prototype model is ready to be tested with an appropriate huge database before the clinical usage.
  8. Tan CE, Lau SCD, Tan KA, Latiff ZA, Teh KH, Lee CC, et al.
    Cureus, 2022 Oct;14(10):e30903.
    PMID: 36465778 DOI: 10.7759/cureus.30903
    Introduction Validated tools to measure caregiving knowledge among parents of children with hematological cancers are needed to measure the clinical outcome of caregiver interventions. This study reports the development and validation of the Hematological Oncology Parents Education Caregiving Knowledge Questionnaire (HOPE-CKQ) among Malaysian parents of pediatric leukemia and lymphoma patients. Methods Initially, 60 items on caregiving knowledge were developed based on a qualitative needs assessment study. Content validity was evaluated using item content validity index (I-CVI) and scale content validity index (S-CVI/Ave). Parents of pediatric leukemia and lymphoma patients were invited to complete the 60-item version of the HOPE-CKQ. Exploratory factor analysis (EFA) using polychoric correlation resulted in an 18-item version of HOPE-CKQ. Confirmatory factor analysis (CFA) was used to verify the factor structure. Known-group validity was tested by comparing the scores among different levels of parent education. Results The I-CVI ranged from 0.83 to 1.00 whereas the S-CVI/Ave was 0.99, indicating good content validity. A total of 167 complete responses were analyzed for factor analysis. EFA using polychoric correlations resulted in a single-factor structure consisting of 18 items. CFA confirmed that the 18-item single-factor HOPE-CKQ model had a good fit for the data. The internal consistency reliability was good (α=0.80). Parents with tertiary education level had higher caregiving knowledge (M=12.61, SD=3.37) compared to parents with secondary education and below (M=10.33, SD=3.80) (t=3.58, p<0.001). Conclusions The 18-item HOPE-CKQ is valid and reliable for use to measure caregiving knowledge among pediatric leukemia and lymphoma parents. This tool may be considered to measure caregiving knowledge in future preventive and intervention programs.
  9. Tan PPS, Sandhu RS, Zain SM, Hall D, Tan NC, Lim HM, et al.
    PLoS One, 2022;17(12):e0278761.
    PMID: 36477162 DOI: 10.1371/journal.pone.0278761
    INTRODUCTION: Self-care behaviour is fundamental in preventing hypertension in the general population. According to the Health Belief Model, health beliefs and perceptions influence the success in adopting disease prevention strategies. While factors influencing hypertension self-care behaviour have been examined previously in patient populations, they have not been assessed in the general community.

    METHODS: This was a cross-sectional study conducted between 12 June 2020 to 26 July 2021. An online survey was administered via email and social media to Malaysians in the Selangor and Kuala Lumpur communities. Respondents were over 18 years old, without a formal diagnosis of hypertension. The survey evaluated hypertension knowledge, Health Belief Model constructs, self-care behaviour frequency, and motivators and barriers to self-care behaviour. Multiple linear regression was performed to determine the main predictors of self-care behaviour, and descriptive statistics were used to characterise motivators and barriers of each self-care behaviour.

    RESULTS: Only health motivations (β = 0.217, p < 0.001) and perceived barriers (β = 0.571, p < 0.001) significantly influenced self-care behaviour. Maintaining a healthy diet, regular physical activity and blood pressure checks need to be improved in the community, particularly in reducing salt and calorie intake. Lack of time, limited choices and laziness are the biggest challenges that need to be tackled in adopting a healthy diet and an active lifestyle in the community. Many are ignorant towards their health status, therefore, do not prioritize blood pressure screenings, suggesting a need to enhance community blood pressure checks for early diagnosis of hypertension.

    CONCLUSION AND IMPLICATIONS: Motivations and barriers were the main determinants of self-care behaviour in the Selangor and Kuala Lumpur community. Targeting these aspects of self-care behaviour should be considered when developing interventions and education programmes tailored to local cultural, environmental and personal factors, to more effectively reduce the hypertension prevalence and burden.

  10. Rashidah NH, Lim SM, Neoh CF, Majeed ABA, Tan MP, Khor HM, et al.
    Ageing Res Rev, 2022 Dec;82:101744.
    PMID: 36202312 DOI: 10.1016/j.arr.2022.101744
    This systematic review appraised previous findings on differential gut microbiota composition and intestinal permeability markers between frail and healthy older adults. A literature search was performed using PubMed, Scopus, ScienceDirect and the Cochrane Library. Relevant studies were shortlisted based on inclusion and exclusion criteria as well as assessed for risk of bias. The primary outcome was the differential composition of gut microbiota and/ or intestinal permeability markers between frail and healthy older adults. A total of 10 case-control studies and one cohort study were shortlisted. Based on consistent findings reported by more than one shortlisted study, the microbiota of frail older adults was characterised by decreased phylum Firmicutes, with Dialister, Lactobacillus and Ruminococcus being the prominent genera. Healthy controls, on the other hand, exhibited higher Eubacterium at the genera level. In terms of intestinal permeability, frail older adults were presented with increased serum zonulin, pro-inflammatory cytokines (TNF-α, HMGB-1, IL-6, IL1-ra, MIP-1β) and amino acids (aspartic acid and phosphoethanolamine) when compared to healthy controls. Altogether, frail elderlies had lower gut microbiota diversity and lower abundance of SCFA producers, which may have led to leaky guts, upregulated pro-inflammatory cytokines, frailty and sarcopenia.
  11. Hor CJ, Tan YH, Mubarak NM, Tan IS, Ibrahim ML, Yek PNY, et al.
    Environ Res, 2023 Mar 01;220:115169.
    PMID: 36587722 DOI: 10.1016/j.envres.2022.115169
    To date, the development of renewable fuels has become a normal phenomenon to solve the problem of diesel fuel emissions and the scarcity of fossil fuels. Biodiesel production has some limitations, such as two-step processes requiring high free fatty acids (FFAs), oil feedstocks and gum formation. Hydrotreated vegetable oil (HVO) is a newly developed international renewable diesel that uses renewable feedstocks via the hydrotreatment process. Unlike FAME, FFAs percentage doesn't affect the HVO production and sustains a higher yield. The improved characteristics of HVO, such as a higher cetane value, better cold flow properties, lower emissions and excellent oxidation stability for storage, stand out from FAME biodiesel. Moreover, HVO is a hydrocarbon without oxygen content, but FAME is an ester with 11% oxygen content which makes it differ in oxidation stability. Waste sludge palm oil (SPO), an abundant non-edible industrial waste, was reused and selected as the feedstock for HVO production. Techno-economical and energy analyses were conducted for HVO production using Aspen HYSYS with a plant capacity of 25,000 kg/h. Alternatively, hydrogen has been recycled to reduce the hydrogen feed. With a capital investment of RM 65.86 million and an annual production cost of RM 332.56 million, the base case of the SPO-HVO production process was more desirable after consideration of all economic indicators and HVO purity. The base case of SPO-HVO production could achieve a return on investment (ROI) of 89.03% with a payback period (PBP) of 1.68 years. The SPO-HVO production in this study has observed a reduction in the primary greenhouse gas, carbon dioxide (CO2) emission by up to 90% and the total annual production cost by nearly RM 450 million. Therefore, SPO-HVO production is a potential and alternative process to produce biobased diesel fuels with waste oil.
  12. Blessmann J, Hanlodsomphou S, Santisouk B, Krumkamp R, Kreuels B, Ismail AK, et al.
    Trop Med Int Health, 2023 Jan;28(1):64-70.
    PMID: 36416013 DOI: 10.1111/tmi.13833
    OBJECTIVES: To evaluate the safety and efficacy of expired lyophilized snake antivenom of Thai origin during a medical emergency in 2020/2021 in Lao People's Democratic Republic.

    METHODS: Observational case series of patients with potentially life-threatening envenoming who consented to the administration of expired antivenom between August 2020 and May 2022.

    RESULTS: A total of 31 patients received the expired antivenom. Malayan pit vipers (Calloselasma rhodostoma) were responsible for 26 (84%) cases and green pit vipers (Trimeresurus species) for two cases (6%). In three patients (10%) the responsible snake could not be identified. Of these, two presented with signs of neurotoxicity and one with coagulopathy. A total of 124 vials of expired antivenom were administered. Fifty-nine vials had expired 2-18 months earlier, 56 vials 19-36 months and nine vials 37-60 months before. Adverse effects of variable severity were observed in seven (23%) patients. All 31 patients fully recovered from systemic envenoming.

    CONCLUSIONS: Under closely controlled conditions and monitoring the use of expired snake antivenom proved to be effective and safe. Discarding this precious medication is an unnecessary waste, and it could be a valuable resource in ameliorating the current shortage of antivenom. Emergency use authorization granted by health authorities and preclinical testing of expired antivenoms could provide the support and legal basis for such an approach.

  13. Tan MC, Tan JL, Lee WJ, Srivathsan K, Sorajja D, El Masry H, et al.
    J Arrhythm, 2023 Oct;39(5):784-789.
    PMID: 37799789 DOI: 10.1002/joa3.12898
    BACKGROUND: Real-world clinical data on the adverse events related to the use of cryoballoon catheter for pulmonary vein isolation remains limited.

    OBJECTIVE: To report and describe the adverse events related to the use of Artic Front cryoballoon catheters (Arctic Front, Arctic Front Advance, and Arctic Front Advance Pro) reported in the Food and Drug Administration's (FDA) Manufacturers and User Defined Experience (MAUDE) database.

    METHODS: We reviewed all the adverse events reported to the FDA MAUDE database over a 10.7-year study period from January 01, 2011 to September 31, 2021. All events were independently reviewed by two physicians.

    RESULTS: During the study period, a total of 320 procedural-related adverse events reported in the MAUDE database were identified. The most common adverse event was transient or persistent phrenic nerve palsy (PNP), accounting for 48% of all events. This was followed by cardiac perforation (15%), pulmonary vein stenosis (8%), transient ischemic attack or stroke (6%), vascular injury (4%), transient or persistent ST-elevation myocardial infarction (3%), hemoptysis (2%), pericarditis (2%), and esophageal ulcer or fistula (1%). There were six reported intra-procedural death events as a result of cardiac perforation.

    CONCLUSION: The two most common procedural adverse events associated with cryoballoon ablation were PNP and cardiac perforation. All cases of procedural mortality were due to cardiac perforation.

  14. Tan GW, Sivanesan VM, Abdul Rahman FI, Hassan F, Hasbullah HH, Ng CC, et al.
    Int J Cancer, 2019 Oct 15;145(8):2260-2266.
    PMID: 30698824 DOI: 10.1002/ijc.32173
    Nasopharyngeal carcinoma (NPC) is an epithelial cancer of the nasopharynx which is highly associated with Epstein-Barr virus (EBV). Worldwide, most of the top 20 countries with the highest incidence and mortality rates of NPC are low- and middle-income countries. Many studies had demonstrated that EBV could be detected in the tissue, serum and plasma of NPC patients. In this study, we explored the potential of assays based on non-invasive nasal washings (NW) as a diagnostic and prognostic tool for NPC. A total of 128 patients were evaluated for NW EBV DNA loads and a subset of these samples were also tested for 27 EBV and human miRNAs shortlisted from literature. EBV DNA and seven miRNAs showed area under the receiver operating characteristic curve (AUC) values of more than 0.7, suggestive of their potential utility to detect NPC. Logistic regression analyses suggested that combination of two NW assays that test for EBNA-1 and hsa-miR-21 had the best performance in detecting NPC. The trend of NW EBV DNA load matched with clinical outcome of 71.4% (10 out of 14) NPC patients being followed-up. In summary, the non-invasive NW testing panel may be particularly useful for NPC screening in remote areas where healthcare facilities and otolaryngologists are lacking, and may encourage frequent testing of individuals in the high risk groups who are reluctant to have their blood tested. However, further validation in an independent cohort is required to strengthen the utility of this testing panel as a non-invasive detection tool for NPC.
  15. Tajunisah I, Tan SS, Effendi-Tenang I, Samsudin A, Ling KP, Tan WY, et al.
    Front Cell Infect Microbiol, 2023;13:1243055.
    PMID: 37790912 DOI: 10.3389/fcimb.2023.1243055
    PURPOSE: We report the ocular findings that patients experienced after receiving the coronavirus disease 2019 (COVID-19) vaccination in three different eye centers in Malaysia.

    OBSERVATIONS: A total of four cases were reported. Three patients received the Pfizer-BioNTech vaccine, while the other received the Oxford AstraZeneca type. Ocular symptoms occurred after the first vaccine dose in two patients and after the second vaccine dose in the other two. Three out of four patients required active treatment for their vision complications postvaccination. The first patient had acute-onset retinal pigment epitheliitis within 3 h of vaccination and was treated conservatively. The second patient developed unilateral choroidal neovascularization 3 days after vaccination and required intravitreal antivascular endothelial growth factor injection. The third patient presented with bilateral acute multifocal placoid pigment epitheliopathy a week after vaccination and responded to intravenous methylprednisolone. The fourth patient presented with herpes zoster infection and unilateral anterior nongranulomatous uveitis 2 weeks after vaccination and was treated with oral acyclovir and topical corticosteroids. All patients reported some amount of visual recovery.

    CONCLUSIONS AND IMPORTANCE: Visual symptoms and various ocular adverse events can occur following COVID-19 vaccination, which warrants further investigation and urgent intervention if necessary. We would suggest patients receiving the COVID-19 vaccination be aware of possible ocular complications and report any symptoms, regardless of severity.

  16. Tan KY, Deng S, Tan TK, Hari R, Sitam FT, Othman RY, et al.
    PeerJ, 2023;11:e16002.
    PMID: 37810781 DOI: 10.7717/peerj.16002
    BACKGROUND: The Malayan pangolin (Manis javanica) is a placental mammal and is listed as Critically Endangered on the IUCN Red List of Threatened Species. Most previous attempts to breed pangolins in captivity have met with little success because of dietary issues, infections, and other complications, although a previous study reported breeding pangolins in captivity to the third generation. In our previous pangolin genome sequencing data analysis, we obtained a considerable amount of bacterial DNA from a pregnant female Malayan pangolin (named "UM3"), which was likely infected by Paraburkholderia fungorum-an agent of biodegradation and bioremediation in agriculture.

    METHODOLOGY: Here, we further confirmed and characterized this bacterial species using PCR, histological staining, whole-genome sequencing, and bioinformatics approaches. PCR assays with in-house designed primer sets and 16S universal primers showed clear positive bands in the cerebrum, cerebellum, lung, and blood of UM3 suggesting that UM3 might have developed septicaemia. Histological staining showed the presence of Gram-negative rod-shaped bacteria in the pangolin brain and lungs, indicating the colonization of the bacteria in these two organs. In addition, PCR screening of UM3's fetal tissues revealed the presence of P. fungorum in the gastrocnemius muscle, but not in other tissues that we examined. We also sequenced and reconstructed the genome of pangolin P. fungorum, which has a genome size of 7.7 Mbps.

    CONCLUSION: Our study is the first to present detailed evidence of the presence of P. fungorum in a pangolin and her fetus (although preliminary results were presented in our previous article). Here, we raise the concern that P. fungorum may potentially infect humans, especially YOPI (young, old, pregnant, and immunocompromised) people. Therefore, caution should be exercised when using this bacterial species as biodegradation or bioremediation agents in agriculture.

  17. Cheah KY, Mah KY, Pang LH, Ng SM, Wong JW, Tan SS, et al.
    BMC Pharmacol Toxicol, 2020 06 23;21(1):45.
    PMID: 32576287 DOI: 10.1186/s40360-020-00416-3
    BACKGROUND: Paracetamol/Orphenadrine is a fixed dose combination containing 35 mg orphenadrine and 450 mg paracetamol. It has analgesic and muscle relaxant properties and is widely available as generics. This study is conducted to investigate the relative bioavailability and bioequivalence between one fixed dose paracetamol/orphenadrine combination test preparation and one fixed dose paracetamol/orphenadrine combination reference preparation in healthy volunteers under fasted condition for marketing authorization in Malaysia.

    METHOD: This is a single-center, single-dose, open-label, randomized, 2-treatment, 2-sequence and 2-period crossover study with a washout period of 7 days. Paracetamol/Orphenadrine tablets were administered after a 10-h fast. Blood samples for pharmacokinetic analysis were collected at scheduled time intervals prior to and up to 72 h after dosing. Blood samples were centrifuged, and separated plasma were kept frozen (- 15 °C to - 25 °C) until analysis. Plasma concentrations of orphenadrine and paracetamol were quantified using liquid-chromatography-tandem mass spectrometer using diphenhydramine as internal standard. The pharmacokinetic parameters AUC0-∞, AUC0-t and Cmax were determined using plasma concentration time profile for both preparations. Bioequivalence was assessed according to the ASEAN guideline acceptance criteria for bioequivalence which is the 90% confidence intervals of AUC0-∞, AUC0-t and Cmax ratio must be within the range of 80.00-125.00%.

    RESULTS: There were 28 healthy subjects enrolled, and 27 subjects completed this trial. There were no significant differences observed between the AUC0-∞, AUC0-t and Cmax of both test and reference preparations in fasted condition. The 90% confidence intervals for the ratio of AUC0-t (100.92-111.27%), AUC0-∞ (96.94-108.08%) and Cmax (100.11-112.50%) for orphenadrine (n = 25); and AUC0-t (94.29-101.83%), AUC0-∞ (94.77-101.68%) and Cmax (87.12-101.20%) for paracetamol (n = 27) for test preparation over reference preparation were all within acceptable bioequivalence range of 80.00-125.00%.

    CONCLUSION: The test preparation is bioequivalent to the reference preparation and can be used interchangeably.

    TRIAL REGISTRATION: NMRR- 17-1266-36,001; registered and approved on 12 September 2017.

  18. Chong CS, Tan JK, Ng BH, Lin ABY, Khoo CS, Rajah R, et al.
    J Clin Neurosci, 2023 Dec;118:132-142.
    PMID: 37935067 DOI: 10.1016/j.jocn.2023.10.012
    BACKGROUND AND OBJECTIVE: People with epilepsy frequently encounter sleep disruptions that can stem from a variety of complex factors. Epilepsy-related sleep disturbance can lead to reduced quality of life and excessive daytime hypersomnolence. Identification of sleep disturbances may help in the overall management of epilepsy patients. This study was conducted to determine the prevalence and predictors of poor sleep quality and daytime sleepiness in epilepsy.

    METHODS: A cross-sectional study on 284 epilepsy patients was performed in a local tertiary centre. The demographic and clinical epilepsy data were collected. The Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) questionnaires were utilised to determine the quality of life and daytime hypersomnolence of epilepsy patients, respectively.

    RESULTS: Poor sleep quality was reported in 78 (27.5%) patients while daytime hypersomnolence was present in 17 (6%) patients. The predictors of poor sleep quality include structural causes (OR = 2.749; 95% CI: 1.436, 5.264, p = 0.002), generalised seizures (OR = 1.959, 95% CI: 1.04, 3.689, p = 0.037), and antiseizure medications such as Carbamazepine (OR = 2.34; 95% CI: 1.095, 5.001, p = 0.028) and Topiramate (OR 2.487; 95% CI: 1.028, 6.014, p = 0.043). Females are 3.797 times more likely score higher in ESS assessment (OR 3.797; 95% CI: 1.064, 13.555 p = 0.04).

    DISCUSSION: Sleep disturbances frequently coexist with epilepsy. Patients should be actively evaluated using the PSQI and ESS questionnaires. It is imperative to identify the key factors that lead to reduced sleep quality and heightened daytime sleepiness in patients with epilepsy, as this is essential to properly manage their condition.

  19. Chin PS, Ang GY, Yu CY, Tan EL, Tee KK, Yin WF, et al.
    J Food Prot, 2018 Feb;81(2):284-289.
    PMID: 29360399 DOI: 10.4315/0362-028X.JFP-17-186
    Listeria spp. are ubiquitous in nature and can be found in various environmental niches such as soil, sewage, river water, plants, and foods, but the most frequently isolated species are Listeria monocytogenes and Listeria innocua. In this study, the presence of Listeria spp. in raw chicken meat and chicken-related products sold in local markets in Klang Valley, Malaysia was investigated. A total of 44 Listeria strains (42 L. innocua and 2 L. welshimeri) were isolated from 106 samples. Antibiotic susceptibility tests of the L. innocua strains revealed a high prevalence of resistance to clindamycin (92.9%), ceftriaxone (76.2%), ampicillin (73.8%), tetracycline (69%), and penicillin G (66.7%). Overall, 31 L. innocua and 1 L. welshimeri strain were multidrug resistant, i.e., nonsusceptible to at least one antimicrobial agent in three or more antibiotic classes. The majority of the L. innocua strains were placed into five AscI pulsogroups, and overall 26 distinct AscI pulsotypes were identified. The detection of multidrug-resistant Listeria strains from different food sources and locations warrants attention because these strains could serve as reservoirs for antimicrobial resistance genes and may facilitate the spread and emergence of other drug-resistant strains.
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