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  1. van der Velde N, Seppala L, Petrovic M, Ryg J, Tan MP, Montero-Odasso M, et al.
    Aging Clin Exp Res, 2022 Oct;34(10):2553-2556.
    PMID: 35829992 DOI: 10.1007/s40520-022-02178-w
  2. Zia A, Kamaruzzaman SB, Tan MP
    Postgrad Med, 2015 Mar;127(2):186-93.
    PMID: 25622817 DOI: 10.1080/00325481.2015.996505
    Hypertension is a highly prevalent condition among older people, but many physicians avoid aggressive treatment in this age group due to concerns about adverse effects such as orthostatic hypotension and falls. Orthostatic hypotension, which also increases in prevalence with increasing age, has been considered to be associated with antihypertensive therapy. Both orthostatic hypotension and antihypertensive medications are considered independent yet closely related predictors for falls among older people. The prescription of antihypertensive therapy among the elderly remains a long-standing controversy in geriatric medicine due to ongoing concerns about potential complications such as falls, despite conclusive evidence supporting the treatment of hypertension even among the very elderly. However, recent evidence suggests a dose-dependent relationship between blood pressure lowering therapy and falls among older individuals with preexisting risk factors for falls. In response to the spate of revisions in hypertension treatment targets for older patients in international guidelines and the recent evidence on antihypertensive therapy and falls, this review article examines the complex relationship between hypertension, antihypertensives, orthostatic hypotension, and falls among older patients.
  3. Zia A, Kamaruzzaman SB, Tan MP
    Postgrad Med, 2015 Apr;127(3):330-7.
    PMID: 25539567 DOI: 10.1080/00325481.2014.996112
    The term polypharmacy has negative connotations due to its association with adverse drug reactions and falls. This spectrum of adverse events widens when polypharmacy occurs among the already vulnerable geriatric population. To date, there is no consensus definition of polypharmacy, and diverse definitions have been used by various researchers, the most common being the consumption of multiple number of medications. Taking multiple medications is considered a risk factor for falls through the adverse effects of drug-drug or drug-disease interactions. Falls studies have determined that taking ≥ 4 drugs is associated with an increased incidence of falls, recurrent falls, and injurious falls. In light of existing evidence, careful and regular medication reviews are advised to reduce the effect of polypharmacy on falls. However, intervention studies on medication reviews and their effectiveness on falls reduction have been scarce. This article reviews and discusses the evidence behind polypharmacy and its association with falls among older individuals, and highlights important areas for future research.
  4. Zia A, Kamaruzzaman S, Myint PK, Tan MP
    Maturitas, 2016 Feb;84:32-7.
    PMID: 26531071 DOI: 10.1016/j.maturitas.2015.10.009
    OBJECTIVE: While the anticholinergic activity of medications has been linked to cognitive decline, few studies have linked anticholinergic burden with falls in older people. We evaluated the relationship between anticholinergic burden and recurrent and injurious falls among community-dwelling older adults.
    STUDY DESIGN: This case-control study was performed on 428 participants aged ≥65 years, 263 cases with two or more falls or one injurious fall in the preceding 12 months, and 165 controls with no falls in the preceding 12 months. Anticholinergic burden was determined using the anticholinergic cognitive burden (ACB) scale. Upper and lower limb functional abilities were assessed with timed up and go (TUG), functional reach (FR) and grip strength (GS). Logistic regression analysis was employed to calculate the mediation effect of TUG, FR and GS on ACB associated falls.
    RESULTS: Univariate analysis revealed a significant association between an ACB score of ≥1 with falls (OR, 1.8; 95% CI; 1.1-3.0; p=0.01) and significantly poorer TUG and FR. The association between ACB≥1 and falls was no longer significant after adjustment for either TUG (OR for ACB associated falls, 1.4; 95% CI, 0.88-2.4; p=0.14) or FR (OR for ACB associated falls, 1.4; 95% CI, 0.89-2.4, p=0.12) but remained significant with GS.
    CONCLUSION: The association between recurrent and injurious falls and the use of any medications listed in the ACB scale was mediated through gait and balance impairment but not by muscular weakness, providing a novel insight into the potential mechanistic link between ACB and falls. Future studies should determine whether TUG and FR measurements could help inform risk to benefit decisions where ACB medications are being considered.
    KEYWORDS: Aged; Anticholinergic Cognitive Burden; Falls; Functional Reach; Scale; Timed up and go
  5. Zia A, Kamaruzzaman SB, Tan MP
    Geriatr Gerontol Int, 2017 Mar;17(3):463-470.
    PMID: 26822931 DOI: 10.1111/ggi.12741
    AIM: The presemt study aimed to determine the association between the risk of recurrent and injurious falls with polypharmacy, fall risk-increasing drugs (FRID) and FRID count among community-dwelling older adults.

    METHODS: Participants (n = 202) were aged ≥65 years with two or more falls or one injurious fall in the past year, whereas controls (n = 156) included volunteers aged ≥65 years with no falls in the past year. A detailed medication history was obtained alongside demographic data. Polypharmacy was defined as "regular use of five or more prescription drugs." FRID were identified as cardiovascular agents, central nervous system drugs, analgesics and endocrine drugs; multiple FRID were defined as two or more FRID. Multiple logistic regression analyses were used to adjust for confounders.

    RESULTS: The use of non-steroidal anti-inflammatory drugs was independently associated with an increased risk of falls. Univariate analyses showed both polypharmacy (OR 2.23, 95% CI 1.39-3.56; P = 0.001) and the use of two or more FRID (OR 2.9, 95% CI 1.9-4.5; P = 0.0001) were significantly more likely amongst fallers. After adjustment for age, sex and comorbidities, blood pressure, and physical performance scores, polypharmacy was no longer associated with falls (OR 1.6, 95% CI 0.9-2.9; P = 0.102), whereas the consumption of two or more FRID remained a significant predictor for falls (OR 2.8, 95% CI 1.4-5.3; P = 0.001).

    CONCLUSIONS: Among high risk fallers, the use of two or more FRID was an independent risk factor for falls instead of polypharmacy. Our findings will inform clinical practice in terms of medication reviews among older adults at higher risk of falls. Future intervention studies will seek to confirm whether avoidance or withdrawal of multiple FRID reduces the risk of future falls. Geriatr Gerontol Int 2017; 17: 463-470.

  6. Zia A, Kamaruzzaman SB, Myint PK, Tan MP
    Eur J Clin Invest, 2015 Oct;45(10):1069-76.
    PMID: 26214159 DOI: 10.1111/eci.12508
    A drop in postural blood pressure (BP) may contribute to falls, while antihypertensives have been considered to induce postural drop or orthostatic hypotension (OH) and falls among older people. However, this relationship between antihypertensives, postural BP and the risk of falls has never been evaluated in a single study.
  7. Zhang HY, Chong MC, Tan MP, Chua YP, Zhang JH
    J Geriatr Phys Ther, 2023 Jul 13.
    PMID: 37439875 DOI: 10.1519/JPT.0000000000000388
    BACKGROUND AND PURPOSE: Sarcopenia is a common muscle disease among the older population, posing an increased risk for functional decline and intervention for loss of independence in daily living. Early detection of sarcopenia among older people before functional decline would be beneficial in enhancing their quality of life. The Asian Working Group for Sarcopenia (AWGS) 2019 recommends the use of 3 screening methods for community-based sarcopenia detection: calf circumference (CC), or the Strength, Assistance in walking, Rise from a chair, Climb stairs, and Falls (SARC-F) questionnaire, or the SARC-F in combination with CC (SARC-CalF) questionnaire. This study aims to compare the relative performance of these 3 methods as screening tools for sarcopenia within a community-dwelling older population.

    METHODS: A total number of 700 community-dwelling older adults participated in the current study. Muscle mass, muscle strength, and physical performance were measured with bioelectrical impedance analysis, handgrip strength, and gait speed, respectively. The AWGS 2019 criteria were considered the criterion standard The sensitivity/specificity, receiver operating characteristic (ROC) curve, and area under the receiver operating characteristic curve (AUROC) analyses were determined for CC, SARC-F, and SARC-CalF to determine their relative diagnostic performance.

    RESULTS: Sarcopenia was identified in 21.4% of participants according to the AWGS2019 criteria. The overall prevalence of sarcopenia was 56.6%, 14.7%, and 22.9% according to CC, SARC-F, and SARC-CalF, respectively. Calf circumference showed the highest sensitivity but lowest specificity based on AWGS 2019 as the criterion standard regardless of age, gender, and body mass index. The SARC-CalF showed better sensitivity but similar specificity than the SARC-F. The AUROC of CC was significantly better than that of SARC-F and SARC-CalF. The AUROCs of CC, SARC-F, and SARC-CalF were statistically significant in all populations, as well as in the categories of age, gender, and body mass index ( P < .05).

    CONCLUSIONS: Calf circumference is useful in ruling out the presence of sarcopenia while the SARC-F is more effective in ruling in sarcopenia, especially in the context of population-based screening. Future studies should be carried out to investigate the value of population-based sarcopenia detection using these screening tools.

  8. Yusof M, Awaluddin SM, Omar M, Ahmad NA, Abdul Aziz FA, Jamaluddin R, et al.
    J Environ Public Health, 2018;2018:1803025.
    PMID: 29853924 DOI: 10.1155/2018/1803025
    Introduction: Anaemia is common among the elderly, yet it remains an underresearched clinical condition. This study investigates ethnic differences in prevalence of anaemia and identifies potential factors associated with anaemia in the elderly.
    Methods: Data from the National Health & Morbidity Survey (NHMS) 2015 conducted by Ministry of Health was analyzed. Haemoglobin levels were measured using point-of-care testing, HemoCue® Hb 201+ System©, from consenting individuals. Demographic information and other clinical information were obtained through a structured questionnaire. Descriptive and multivariate analyses were conducted and significant results were presented as adjusted odds ratio.
    Results: A total of 3794 participants aged 60 years and older responded to the anaemia module with a response rate of 93.7%. 64.0% of respondents were of Malay ethnicity, 21.6% were Chinese, 6.1% were Indians, and 8.3% were of other ethnicities. The overall prevalence of anaemia among older people was 35.3%. The highest prevalence of anaemia was found among respondents of Indian ethnicity (45.5%). The Indian (aOR: 1.72; 95% CI 1.26-2.34) and Malay (aOR: 1.25; 95% CI 1.04-1.49) ethnic groups were more likely to be anaemic in comparison to those of Chinese ethnicity. Anaemia in older people was also associated with increasing age, history of hospital admission, and the presence of diabetes mellitus.
    Conclusion: Anaemia in the elderly is associated with Indian and Malay ethnicities, increasing age, hospitalization, and diabetes. Our study has identified important information on a common condition which will guide and assist future studies in reducing the burden of anaemia.
    Study name: National Health and Morbidity Survey (NHMS-2015)
  9. Yunus RM, Hairi NN, Choo WY, Tan MP, Hairi F, Sooryanarayana R, et al.
    J Am Geriatr Soc, 2018 07;66(6):1165-1171.
    PMID: 29601084 DOI: 10.1111/jgs.15370
    OBJECTIVES: To examine the cross-sectional and longitudinal relationships between elder abuse and neglect (EAN) and chronic pain in rural older Malaysians.

    DESIGN: Two-year prospective cohort study.

    SETTING: Kuala Pilah, a district in Negeri Sembilan approximately 100 km from the capital city, Kuala Lumpur.

    PARTICIPANTS: Community-dwelling older adults aged 60 and older. Using a multistage cluster sampling strategy, 1,927 respondents were recruited and assessed at baseline, of whom 1,189 were re-assessed 2 years later.

    MEASURES: EAN was determined using the modified Conflict Tactic Scale, and chronic pain was assessed through self-report using validated questions.

    RESULTS: The prevalence of chronic pain was 20.4%. Cross-sectional results revealed 8 variables significantly associated with chronic pain-age, education, income, comorbidities, self-rated health, depression, gait speed, and EAN. Abused elderly adults were 1.52 times as likely to have chronic pain (odds ratio=1.52, 95% confidence interval (CI)=1.03-2.27), although longitudinal analyses showed no relationship between EAN and risk of chronic pain (risk ratio=1.14, 95% CI=0.81-1.60). This lack of causal link was consistent when comparing analysis with complete cases with that of imputed data.

    CONCLUSION: Our findings indicate no temporal relationship between EAN and chronic pain but indicated cross-sectional associations between the two. This might indicate that, although EAN does not lead to chronic pain, individuals with greater physical limitations are more vulnerable to abuse. Our study also shows the importance of cohort design in determining causal relationships between EAN and potentially linked health outcomes.

  10. Yong SS, Kwan Z, Ch'ng CC, Yong ASW, Tan LL, Han WH, et al.
    BMC Geriatr, 2020 06 24;20(1):223.
    PMID: 32580764 DOI: 10.1186/s12877-020-01610-y
    BACKGROUND: The ageing skin is more susceptible to pruritic dermatoses, which are associated with adverse psychosocial effects and reduced quality of life among older adults. This cross-sectional study aimed to identify the burden of pruritus and factors associated with its presence and severity among older adults recruited to the Malaysian Elders Longitudinal Research study.

    METHODS: Seven hundred seventy individuals aged 55 years (lower age limit) and above were interviewed as to whether they experienced pruritus during the preceding week and the locations involved if present. The association between generalised pruritus, sleep quality, and major systemic risk factors were explored.

    RESULTS: 5.97% of respondents reported generalised pruritus. Generalised pruritus was associated with poorer sleep quality, with Pittsburgh Sleep Quality Index score above 6. Mean haemoglobin level was lower in subjects with generalised pruritus (13.14 g/dL) but there was no significant difference in the frequency of generalised pruritus and severe generalized pruritus between subjects with clinically defined anaemia. Also, there were no significant associations between other major systemic risk factors and generalised pruritus in this population-based study. There was no association between generalised pruritus with depression, anxiety or stress.

    CONCLUSION: The negative effect of pruritus on sleep quality suggests a possible deleterious effect of pruritus on health and quality of life. Further prospective research on the longer-term effects of pruritus on health status is now warranted. (222 words).

  11. Yeap SS, Tanavalee A, Perez EC, Tan MP, Reyes BHM, Lee JK, et al.
    Aging Clin Exp Res, 2021 May;33(5):1149-1156.
    PMID: 33774784 DOI: 10.1007/s40520-021-01834-x
    BACKGROUND: Since 2014, the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) algorithm for the management of knee osteoarthritis (OA) is available worldwide.

    AIM: Based on this document, a Southeast Asia Working Group (SEAWG) wished to see how the new ESCEO algorithm developed in 2019 was perceived by Southeast Asian experts and how it was integrated into their clinical practice.

    METHODS: A SEAWG was set up between members of the international ESCEO task force and a group of Southeast Asian experts.

    RESULTS: Non-pharmacological management should always be combined with pharmacological management. In step 1, symptomatic slow-acting drugs for osteoarthritis are the main background therapy, for which high-quality evidence is available only for the formulations of patented crystalline glucosamine sulfate and chondroitin sulfate. In step 2, oral NSAIDs are a useful option, considering the cardiovascular/renal/gastrointestinal profiles of the individual patient. Intra-articular hyaluronic acid and corticosteroids are a possible alternative to oral NSAIDs, but limited evidence is available. If steps 1 and 2 do not give adequate relief of symptoms, tramadol can be used, but its safety is debated. In general, the indications of the ESCEO algorithm are important in Southeast Asian countries, but the reimbursement criteria of local health systems are an important aspect for adherence to the ESCEO algorithm.

    CONCLUSION: This guidance provides evidence-based and easy-to-follow advice on how to establish a treatment algorithm in knee OA, for practical implementation in clinical practice in Southeast Asian countries.

  12. Yeap SS, Abu Amin SR, Baharuddin H, Koh KC, Lee JK, Lee VKM, et al.
    BMC Musculoskelet Disord, 2021 Jun 04;22(1):514.
    PMID: 34088302 DOI: 10.1186/s12891-021-04381-8
    BACKGROUND: The 2013 Malaysian Clinical Practice Guidelines on the Management of Osteoarthritis (OA) recommend a linear step-up approach to manage knee OA. However, patients with knee OA often require a multimodal approach to address OA-related pain symptoms and functional limitations. This consensus aimed to provide doctors with an updated set of evidence-based, clinical experience-guided recommendations to manage knee OA.

    METHODS: A multi-speciality expert panel consisting of nine Malaysian physicians from different healthcare settings who manage a diverse OA patient population was convened. Using a combination of the ADAPTE process and modified Delphi method, the panel reviewed current evidence on the management of knee OA and synthesised a set of nine recommendations on the management of knee OA, supported by an algorithm that summarises the consensus' core messages.

    RESULTS: A multimodal intervention strategy is the mainstay of OA management and the choice of any single or multimodal intervention may vary over the course of the disease. Overall, a non-pharmacological core treatment set of patient education, weight loss and exercise is recommended for all patients. When pharmacotherapy is indicated, symptomatic slow-acting drugs for osteoarthritis are recommended at the early stage of disease, and they can be paired with physical therapy as background treatment. Concurrent advanced pharmacotherapy that includes non-steroidal anti-inflammatory drugs, intraarticular injections and short-term weak opioids can be considered if patients do not respond sufficiently to background treatment. Patients with severe symptomatic knee OA should be considered for knee replacement surgery. Management should begin with specific treatments with the least systemic exposure or toxicity, and the choice of treatment should be determined as a shared decision between patients and their team of healthcare providers.

    CONCLUSIONS: This consensus presents nine recommendations that advocate an algorithmic approach in the management of patients living with knee OA. They are applicable to patients receiving treatment from primary to tertiary care providers in Malaysia as well as other countries.

  13. Yasin RM, Tan MP, Said MA, Rasul MS, Thangiah N, Rizal H, et al.
    Front Public Health, 2024;12:1164056.
    PMID: 38504686 DOI: 10.3389/fpubh.2024.1164056
    INTRODUCTION: Education improves the economy and quality of life. The availability of skilled education in Malaysia is not restricted to the younger generation but is available to people of all ages, including those with low incomes.

    METHODS: This study used the EuroQol 5-Dimension 5-Level (EQ- 5D-5L) tool during the COVID-19 pandemic to examine relationships between socio-demographics, knowledge, and attitudes towards education and outcomes of health-related quality of life (HRQOL). Between September and October 2020 and January and February 2021, a cross-sectional study using a multi-stage sampling technique was carried out.

    RESULTS: A total of 1,997 adults participated, with a mean age of 45.17 (SD 14.113). In total, 74.9% had good knowledge, while 59.8% had a positive attitude towards skill education. In univariate analyses, the EQ-5D-5L score was related to age, income, education level, marital status, employment status, financial strain level, and knowledge and attitude towards skilled education. Generalised linear model analyses demonstrated that lower EQ-5D-5L scores were associated with older age, financial constraints, and a negative attitude towards skills education. However, additional adjustments for knowledge and attitude towards skills education show only an increase in age and financial strain was significant.

    CONCLUSION: The findings suggest that appropriate strategies be implemented to increase low-income populations' knowledge and attitude towards skill education. Improving education may improve the quality of life for this vulnerable group. Additionally, a qualitative study can be conducted to determine the barriers to low-income households participating in skilled education to fill in the knowledge gap.

  14. Yamada M, Lee WJ, Akishita M, Yang M, Kang L, Kim S, et al.
    Arch Gerontol Geriatr, 2023 Dec;115:105132.
    PMID: 37490804 DOI: 10.1016/j.archger.2023.105132
    OBJECTIVE: This study aimed to (1) investigate the clinical practice for the management of sarcopenia among healthcare professionals in Asia, (2) determine the characteristics of clinical care provided by geriatricians versus by other healthcare professionals, and (3) clarify the awareness of sarcopenia.

    METHODS: From December 1 to 31, 2022, an online survey was completed by 1990 healthcare professionals in Asia. The survey comprises demographics and institutional characteristics, basic sarcopenia-related details, and sarcopenia-related assessment and treatment details.

    RESULTS: The mean respondent age was 44.2 ± 10.7 years, 36.4% of the respondents were women, and the mean years of experience in clinical practice were 19.0 ± 10.6 years. The percentages of respondents who were aware of the term "sarcopenia", its definition and the importance of its management were high, at 99.3%, 91.9%, and 97.2%, respectively. The percentages of respondents who had screened patients for, diagnosed patients with, and treated patients for sarcopenia were 42.4%, 42.9%, and 58.8%, respectively. Medical doctors had higher performance rates compared to allied health professionals (45.5% vs. 40.5% for screening, 56.8% vs. 34.5% for diagnosis, and 65.0% vs. 55.0% for treatment) (P 

  15. Xu XJ, Myint PK, Kioh SH, Mat S, Rajasuriar R, Kamaruzzaman SB, et al.
    Arch Gerontol Geriatr, 2021 09 30;98:104535.
    PMID: 34601313 DOI: 10.1016/j.archger.2021.104535
    BACKGROUND: While anticholinergic use is associated with stroke, dementia and mortality, few have evaluated its potential link with falls. To determine the relationship between anticholinergic cognitive burden (ACB) and falls over five years using the Malaysian Elders Longitudinal Research (MELoR).

    METHODS: Community-dwelling adults aged 55 years and over were recruited through electoral roll sampling. Data obtained at baseline and follow-up (FU) at two and five years were included. Falls in the preceding 12 months were recorded.

    RESULTS: Of the 1499 individuals (mean (SD) age= 68.9(7.5) yrs and 53.3% female) with information on baseline ACB exposure, 575(38.4%) had ACB scores of 1-2 and 117(7.8%) had ACB scores ≥3. Differences in age, ethnicity, smoking status, diabetes, hypertension, cardiovascular disease, arthritis and education existed between ACB groups. Fall occurrence differed between ACB groups at recruitment (p = 0.004) and 2-year FU (p = 0.001) but not at 5-year FU (p = 0.053). Logistic regression revealed an independent association between ACB 1-2 and falls at baseline (odds ratio, OR (95% confidence interval, CI) =1.412(1.035-1.926)) and ACB≥3 and falls at 2-yr FU (OR (95%CI) =2.098(1.032-4.263)) following adjustment for confounders.

    CONCLUSION: Low level exposure to drugs with anticholinergic properties was associated cross-sectionally with falls, while exposure to higher levels were prospectively associated with falls at 2-year but not at 5-year FU. Future studies should determine whether avoidance of drugs with anticholinergic effects will lead to reduction in falls.

  16. Wong YQ, Tan LK, Seow P, Tan MP, Abd Kadir KA, Vijayananthan A, et al.
    PLoS One, 2017;12(6):e0179895.
    PMID: 28658309 DOI: 10.1371/journal.pone.0179895
    OBJECTIVES: This study assesses the whole brain microstructural integrity of white matter tracts (WMT) among older individuals with a history of falls compared to non-fallers.

    METHODS: 85 participants (43 fallers, 42 non-fallers) were evaluated with conventional MRI and diffusion tensor imaging (DTI) sequences of the brain. DTI metrics were obtained from selected WMT using tract-based spatial statistics (TBSS) method. This was followed by binary logistic regression to investigate the clinical variables that could act as confounding elements on the outcomes. The TBSS analysis was then repeated, but this time including all significant predictor variables from the regression analysis as TBSS covariates.

    RESULTS: The mean diffusivity (MD) and axial diffusivity (AD) and to a lesser extent radial diffusivity (RD) values of the projection fibers and commissural bundles were significantly different in fallers (p < 0.05) compared to non-fallers. However, the final logistic regression model obtained showed that only functional reach, white matter lesion volume, hypertension and orthostatic hypotension demonstrated statistical significant differences between fallers and non-fallers. No significant differences were found in the DTI metrics when taking into account age and the four variables as covariates in the repeated analysis.

    CONCLUSION: This DTI study of 85 subjects, do not support DTI metrics as a singular factor that contributes independently to the fall outcomes. Other clinical and imaging factors have to be taken into account.

  17. Wong PL, Sii HL, P'ng CK, Ee SS, Yong Oong X, Ng KT, et al.
    Influenza Other Respir Viruses, 2020 05;14(3):286-293.
    PMID: 32022411 DOI: 10.1111/irv.12691
    BACKGROUND: Age is an established risk factor for poor outcomes in individuals with influenza-related illness, and data on its influence on clinical presentations and outcomes in the South-East Asian settings are scarce. The aim of this study was to determine the above among adults with influenza-related upper respiratory tract infection at a teaching hospital in Malaysia.

    METHODS: A retrospective case-note analysis was conducted on a cohort of 3935 patients attending primary care at the University Malaya Medical Centre, Malaysia from February 2012 till May 2014 with URTI symptoms. Demographics, clinical characteristics, medical and vaccination history were obtained from electronic medical records, and mortality data from the National Registration Department. Comparisons were made between those aged <25, ≥25 to <65 and ≥65 years.

    RESULTS: 470 (11.9%) had PCR-confirmed influenza virus infection. Six (1.3%) received prior influenza vaccination. Those aged ≥65 years were more likely to have ≥2 comorbidities (P 

  18. Wong LP, Alias H, Md Fuzi AA, Omar IS, Mohamad Nor A, Tan MP, et al.
    PLoS One, 2021;16(3):e0248916.
    PMID: 33765039 DOI: 10.1371/journal.pone.0248916
    Since the first nationwide movement control order was implemented on 18 March 2020 in Malaysia to contain the coronavirus disease 2019 (COVID-19) outbreak, to what extent the uncertainty and continuous containment measures have imposed psychological burdens on the population is unknown. This study aimed to measure the level of mental health of the Malaysian public approximately 2 months after the pandemic's onset. Between 12 May and 5 September 2020, an anonymous online survey was conducted. The target group included all members of the Malaysian population aged 18 years and above. The Depression Anxiety Stress Scale (DASS-21) was used to assess mental health. There were increased depressive, anxiety and stress symptoms throughout the study period, with the depression rates showing the greatest increase. During the end of the data collection period (4 August-5 September 2020), there were high percentages of reported depressive (59.2%) and anxiety (55.1%) symptoms compared with stress (30.6%) symptoms. Perceived health status was the strongest significant predictor for depressive and anxiety symptoms. Individuals with a poorer health perception had higher odds of developing depression (odds ratio [OR] = 5.68; 95% confidence interval [CI] 3.81-8.47) and anxiety (OR = 3.50; 95%CI 2.37-5.17) compared with those with a higher health perception. By demographics, young people-particularly students, females and people with poor financial conditions-were more vulnerable to mental health symptoms. These findings provide an urgent call for increased attention to detect and provide intervention strategies to combat the increasing rate of mental health problems in the ongoing COVID-19 pandemic.
  19. Vijayanathan Y, Hamzah NM, Lim SM, Lim FT, Tan MP, Majeed ABA, et al.
    Brain Res Bull, 2022 Nov;190:218-233.
    PMID: 36228872 DOI: 10.1016/j.brainresbull.2022.10.001
    In order to understand the biological processes underlying dopaminergic neurons (DpN) regeneration in a 6-hydroxydopamine(6-OHDA)-induced adult zebrafish-based Parkinson's disease model, this study investigated the specific phases of neuroregeneration in a time-based manner. Bromodeoxyuridine (BrdU) was administered 24 h before the harvest of brain tissues at day three, five, seven, nine, 12 and 14 postlesion. Potential migration of proliferative cells was tracked over 14 days postlesion through double-pulse tracking [BrdU and 5-ethynyl-2'-deoxyuridine (EdU)] of cells and immunohistostaining of astrocytes [glial fibrillary acidic protein (GFAP)]. Gene expression of foxa2 and nurr1 (nr4a2a) at day three, nine, 14, 18, 22 and 30 postlesion was quantified using qPCR. Protein expression of foxa2 at day three, seven, 14 and 22 postlesion was validated using the western blot technique. Double labelling [EdU and tyrosine hydroxylase (TH)] of proliferative cells was performed to ascertain their fate after the neuroregeneration processes. It was found that whilst cell proliferation remained unchanged in the area of substantial DpN loss, the ventral diencephalon (vDn), there was a transient increase of cell proliferation in the olfactory bulb (OB) and telencephalon (Tel) seven days postlesion. BrdU-immunoreactive (ir)/ EdU-ir cells and activated astrocytes were later found to be significantly increased in the vDn and its nearby area (Tel) 14 days postlesion. There was a significant but transient downregulation of foxa2 at day three and nine postlesion, and nr4a2a at day three, nine and 14 postlesion. The expression of both genes remained unchanged in the OB and Tel. There was a transient downregulation of foxa2 protein expression at day three and seven postlesion. The significant increase of EdU-ir/ TH-ir cells in the vDn 30 days postlesion indicates maturation of proliferative cells (formed between day five-seven postlesion) into DpN. The present findings warrant future investigation of critical factors that govern the distinctive phases of DpN regeneration.
  20. Vijayanathan Y, Lim FT, Lim SM, Long CM, Tan MP, Majeed ABA, et al.
    Neurotox Res, 2017 Oct;32(3):496-508.
    PMID: 28707266 DOI: 10.1007/s12640-017-9778-x
    Conventional mammalian models of neurodegeneration are often limited by futile axonogenesis with minimal functional recuperation of severed neurons. The emergence of zebrafish, a non-mammalian model with excellent neuroregenerative properties, may address these limitations. This study aimed to establish an adult zebrafish-based, neurotoxin-induced Parkinson's disease (PD) model and subsequently validate the regenerative capability of dopaminergic neurons (DpN). The DpN of adult male zebrafish (Danio rerio) were lesioned by microinjecting 6-hydroxydopamine (6-OHDA) neurotoxin (6.25, 12.5, 18.75, 25, 37.5, 50 and 100 mg/kg) into the ventral diencephalon (Dn). This was facilitated by an optimised protocol that utilised 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanineperchlorate (DiI) dye to precisely identify the injection site. Immunostaining was utilised to identify the number of tyrosine hydroxylase immunoreactive (TH-ir) DpN in brain regions of interest (i.e. olfactory bulb, telencephalon, preoptic area, posterior tuberculum and hypothalamus). Open tank video recordings were performed for locomotor studies. The Dn was accessed by setting the injection angle of the microinjection capillary to 60° and injection depth to 1200 μm (from the exposed brain surface). 6-OHDA (25 mg/kg) successfully ablated >85% of the Dn DpN (preoptic area, posterior tuberculum and hypothalamus) whilst maintaining a 100% survival. Locomotor analysis of 5-min recordings revealed that 6-OHDA-lesioned adult zebrafish were significantly (p 
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