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  1. Russell V, Loo CE, Walsh A, Bharathy A, Vasudevan U, Looi I, et al.
    BMJ Open, 2021 06 30;11(6):e043923.
    PMID: 34193478 DOI: 10.1136/bmjopen-2020-043923
    OBJECTIVES: To explore primary care clinician perceptions of barriers and facilitators in delivering care for common mental disorders (CMD) before and after implementation of a consultation-liaison psychiatry service (Psychiatry in Primary Care (PIPC)) in government-operated primary care clinics and to explore the clinicians' experience of the PIPC service itself.

    DESIGN: This longitudinal qualitative study was informed by the Normalisation Process Model and involved audiotaped semi-structured individual interviews with front-line clinicians before (Time 1) and after (Time 2) the PIPC intervention. The Framework Method was used in the thematic analysis of pre/post interview transcripts.

    SETTING: Two government-operated primary care clinics in Penang, Malaysia.

    PARTICIPANTS: 17 primary care medical, nursing and allied health staff recruited purposely to achieve a range of disciplines and a balanced representation from both clinics.

    INTERVENTION: Psychiatrists, accompanied by medical students in small numbers, provided one half-day consultation visit per week, to front-line clinicians in each clinic over an 8-month period. The service involved psychiatric assessment of patients with suspected CMDs, with face-to-face discussion with the referring clinician before and after the patient assessment.

    RESULTS: At Time 1 interviewees tended to equate CMDs with stress and embraced a holistic model of care while also reporting considerable autonomy in mental healthcare and positively appraising their current practices. At Time 2, post-intervention, participants demonstrated a shift towards greater understanding of CMDs as treatable conditions. They reported time pressures and the demands of key performance indicators in other areas as barriers to participation in PIPC. Yet they showed increased awareness of current service deficits and of their potential in delivering improved mental healthcare.

    CONCLUSIONS: Despite resource-related and structural barriers to implementation of national mental health policy in Malaysian primary care settings, our findings suggest that front-line clinicians are receptive to future interventions designed to improve the mental healthcare capacity.

  2. Ganasegeran K, Jamil MFA, Ch'ng ASH, Looi I, Peariasamy KM
    Int J Environ Res Public Health, 2021 Sep 18;18(18).
    PMID: 34574790 DOI: 10.3390/ijerph18189866
    The rapid transmission of highly contagious infectious diseases within communities can yield potential hotspots or clusters across geographies. For COVID-19, the impact of population density on transmission models demonstrates mixed findings. This study aims to determine the correlations between population density, clusters, and COVID-19 incidence across districts and regions in Malaysia. This countrywide ecological study was conducted between 22 January 2021 and 4 February 2021 involving 51,476 active COVID-19 cases during Malaysia's third wave of the pandemic, prior to the reimplementation of lockdowns. Population data from multiple sources was aggregated and spatial analytics were performed to visualize distributional choropleths of COVID-19 cases in relation to population density. Hierarchical cluster analysis was used to synthesize dendrograms to demarcate potential clusters against population density. Region-wise correlations and simple linear regression models were deduced to observe the strength of the correlations and the propagation effects of COVID-19 infections relative to population density. Distributional heats in choropleths and cluster analysis showed that districts with a high number of inhabitants and a high population density had a greater number of cases in proportion to the population in that area. The Central region had the strongest correlation between COVID-19 cases and population density (r = 0.912; 95% CI 0.911, 0.913; p < 0.001). The propagation effect and the spread of disease was greater in urbanized districts or cities. Population density is an important factor for the spread of COVID-19 in Malaysia.
  3. Kandiah N, Pai MC, Senanarong V, Looi I, Ampil E, Park KW, et al.
    Clin Interv Aging, 2017;12:697-707.
    PMID: 28458525 DOI: 10.2147/CIA.S129145
    Several studies have demonstrated clinical benefits of sustained cholinesterase inhibition with rivastigmine in Alzheimer's disease (AD) and Parkinson's disease dementia (PDD). Unlike donepezil and galantamine that selectively inhibit acetylcholinesterase (AChE; EC 3.1.1.7), rivastigmine is a unique cholinesterase inhibitor with both AChE and butyrylcholinesterase (BuChE; EC 3.1.1.8) inhibitory activity. Rivastigmine is also available as transdermal patch that has been approved by the US Food and Drug Administration for the treatment of mild, moderate, and severe AD as well as mild-to-moderate PDD. In this review, we explore the role of BuChE inhibition in addition to AChE inhibition with rivastigmine in the outcomes of cognition, global function, behavioral symptoms, and activities of daily living. Additionally, we review the evidence supporting the use of dual AChE-BuChE inhibitory activity of rivastigmine as a therapeutic strategy in the treatment of neurological disorders, with a focus on the role of rivastigmine in subcortical dementias such as vascular dementia (VaD) and PDD. Toward this objective, we performed a literature search in PubMed and Ovid with limits to articles published in the English language before June 2016. The available evidence from the literature suggests that the dual inhibition of AChE and BuChE may afford additional therapeutic potential of rivastigmine in subcortical dementias (subcortical VaD and PDD) with benefits on cognition and behavioral symptoms. Rivastigmine was found to specifically benefit executive dysfunction frequently observed in subcortical dementias; however, large randomized clinical studies are warranted to support these observations.
  4. Mak WY, Ooi QX, Cruz CV, Looi I, Yuen KH, Standing JF
    Br J Clin Pharmacol, 2023 Jan;89(1):330-339.
    PMID: 35976674 DOI: 10.1111/bcp.15496
    AIM: nlmixr offers first-order conditional estimation (FOCE), FOCE with interaction (FOCEi) and stochastic approximation estimation-maximisation (SAEM) to fit nonlinear mixed-effect models (NLMEM). We modelled metformin's pharmacokinetic data using nlmixr and investigated SAEM and FOCEi's performance with respect to bias and precision of parameter estimates, and robustness to initial estimates.

    METHOD: Compartmental models were fitted. The final model was determined based on the objective function value and inspection of goodness-of-fit plots. The bias and precision of parameter estimates were compared between SAEM and FOCEi using stochastic simulations and estimations. For robustness, parameters were re-estimated as the initial estimates were perturbed 100 times and resultant changes evaluated.

    RESULTS: The absorption kinetics of metformin depend significantly on food status. Under the fasted state, the first-order absorption into the central compartment was preceded by zero-order infusion into the depot compartment, whereas for the fed state, the absorption into the depot was instantaneous followed by first-order absorption from depot into the central compartment. The means of relative mean estimation error (rMEE) ( ME E SAEM ME E FOCEi ) and rRMSE ( RMS E SAEM RMS E FOCEi ) were 0.48 and 0.35, respectively. All parameter estimates given by SAEM appeared to be narrowly distributed and were close to the true value used for simulation. In contrast, the distribution of estimates from FOCEi were skewed and more biased. When initial estimates were perturbed, FOCEi estimates were more biased and imprecise.

    DISCUSSION: nlmixr is reliable for NLMEM. SAEM was superior to FOCEi in terms of bias and precision, and more robust against initial estimate perturbations.

  5. Ho YH, Lim CT, Albart SA, Schee JP, Yong MC, Looi I
    Med J Malaysia, 2023 Jan;78(1):1-6.
    PMID: 36715183
    INTRODUCTION: Tuberculosis (TB) in Malaysia has estimated incidence and mortality rates of 81 cases per 100,000 people-year and 4.9 per 100,000 populations, respectively. This study aimed to study the characteristics of rural TB patients and their mortality outcomes.

    MATERIALS AND METHODS: This is a retrospective observational study involving real-world data analysis, looking into TB patients in Lubok Antu Health Clinic by obtaining data through clinic cards, from 1 January 2019 till 31 December 2020. Statistical significance was p < 0.05.

    RESULTS: Eighty-four patients were included. Fifty-two (61.9%) were male. Median age was 58.5 (39-67). Forty-six (54.8%) had smear-positive TB. Seventy-eight (92.9%) were alive at treatment completion. Fifteen (17.9%) experienced adverse drug reactions. Estimated prevalence and mortality rate were 7.1% and 10.7 per 100,000 populations, respectively. Regression analyses revealed that drug reaction was significantly associated with compliance [OR = 8.38 (95% CI: 1.26, 55.53), p = 0.029]. Patients compliant with treatment were more likely to survive [OR = 12.5 (95% CI: 1.61, 97.34), p = 0.028].

    CONCLUSION: Compliance with TB treatment should be emphasised to reduce TB-related mortality.

  6. Elhefnawy M, Nazifah Sidek N, Maisharah Sheikh Ghadzi S, Ibrahim B, Looi I, Abdul Aziz Z, et al.
    Cureus, 2024 Jan;16(1):e52574.
    PMID: 38371076 DOI: 10.7759/cureus.52574
    BACKGROUND: Hyperglycaemia (HG) during an acute ischemic stroke (AIS) is not only associated with unfavourable functional outcomes but also associated with stroke-associated pneumonia (SAP). This study aimed to determine the prevalence of SAP among Malaysian patients with AIS and the predictors of SAP among patients with HG during AIS.

    METHODS: This is a retrospective cross-sectional study that included patients with AIS admitted to Hospital Sultanah Nur Zahirah, Malaysia from 2017 to 2020. SAP was defined as infection with pneumonia during the first seven days after IS. HG was defined as a blood glucose level > 7.8 mmol/L within 72 h after admission. Patients with SAP were divided into two groups according to HG status. Multivariate logistic regression analysis was performed using SPSS software, version 22 (IBM Corp., Armonk, NY) to identify SAP predictors among patients with HG. Kaplan-Meier log-rank test was used to compare the survival rate from unfavourable functional outcomes between hyperglycaemic patients with and without SAP.

    RESULTS: Among 412 patients with AIS, 69 (16.74%) had SAP. The prevalence of SAP among patients with HG and normoglycemia during AIS was 20.98%, and 10.65%, respectively. Age above 60 years, leucocytosis, and National Institute of Health Stroke Scale (NIHSS) > 14 on admission were independent predictors of SAP with aOR of 2.08 (95% CI;1.01-4.30), 2.83 (95% CI; 1.41-5.67), and 3.67 (95% CI; 1.53-8.80), respectively. No significant difference in unfavourable functional outcomes survival was found among patients with and without SAP (p = 0.653).

    CONCLUSION: This study demonstrated the prevalence of SAP was higher among patients with HG compared to normoglycemia during AIS. The patient being old, leucocytosis and severe stroke upon admission predict the occurrence of SAP among patients with HG during AIS.

  7. Loh HC, Looi I, Ch'ng ASH, Goh KW, Ming LC, Ang KH
    GeoJournal, 2022;87(5):4425-4437.
    PMID: 34316088 DOI: 10.1007/s10708-021-10475-6
    Global environmental change is mainly due to human behaviours and is a major threat to sustainability. Despite all the health and economic consequences, the impact of the COVID-19 pandemic lockdown on environmental health warrants the scientific community's attention. Thus, this article examined and narratively reviewed the impact of several drastic measures taken on the macro environment and holistic planetary health. We note that the amount of pollution in the air, water, soil, and noise showed a significant decline during the pandemic. Global air quality improved due to lower anthropogenic emissions of air pollutants and atmospheric particles. Water ecosystems also demonstrated signs of recuperation in many countries. Less commercial fishing internationally resulted in the restoration of some aquatic life. Additionally, significant reduction of solid and water waste led to less soil pollution. Some places experienced cleaner beaches and ocean water while wildlife sightings in urban areas across the world occurred more often. Lastly, the COVID-19 pandemic lockdown also led to a worldwide decline in noise pollution. However, the beneficial environmental effects will not be permanent as the world gradually returns to its pre-pandemic status quo. Therefore, behavioural changes such as adopting a lifestyle that reduces carbon footprint are needed to make a positive impact on the environment. In addition, world leaders should consider the national policy changes necessary to ensure continuity of as many of the positive environmental impacts from the COVID-19 pandemic lockdown as possible. Those changes would also serve to lessen the likelihood of another zoonotic calamity.
  8. Albart SA, Yusof Khan AHK, Abdul Rashid A, Wan Zaidi WA, Looi I, Hoo FK
    Malays J Med Sci, 2024 Aug;31(4):195-212.
    PMID: 39247119 DOI: 10.21315/mjms2024.31.4.16
    BACKGROUND: The Stroke e-Learning Module (SEM) is a nationwide initiative to improve stroke care in Malaysia. This study aimed to assess the module's effectiveness in improving knowledge on acute ischaemic stroke (AIS) management among Malaysian doctors.

    METHODS: This was a pre-post study design. Medical officers, specialists and general practitioners from various disciplines who work in healthcare facilities in Malaysia were recruited virtually from those who registered for the SEM on the Docquity platform between 1 February 2021 and 31 January 2022. The Acute Stroke Management Questionnaire (ASMaQ), an existing validated questionnaire, was used to measure the doctors' knowledge of AIS management before and after the SEM. The ASMaQ had three domains: i) general stroke knowledge (GSK), ii) hyperacute stroke management (HSM) and iii) advanced stroke management (ASM). The paired t- and the McNemar-tests were used to evaluate the effectiveness of the module.

    RESULTS: One hundred and seventy-one participants voluntarily responded to the pre- and post-module questionnaires. The paired t-test revealed statistically significant improvement for the ASM knowledge scores (mean difference = 2.5; 95% CI: 1.8, 3.2; P < 0.001). The baseline proportion of participants with good knowledge of GSK, HSM and ASM were 92.4%, 64.9%, and 76%, respectively. The McNemar test showed that approximately 14% of the participants had significant improvement in ASM knowledge (P < 0.001). However, no significant changes were noted for GSK (-0.6%) and HSM (4.1%).

    CONCLUSION: The SEM has been shown to increase Malaysian doctors' knowledge on ASM. However, greater effort should be made to improve GSK and HSM knowledge, particularly in areas related to stroke thrombolysis.

  9. Hassan Y, Aziz NA, Al-Jabi SW, Looi I, Zyoud SH
    J Cardiovasc Pharmacol Ther, 2010 Sep;15(3):274-81.
    PMID: 20624923 DOI: 10.1177/1074248410373751
    Angiotensin-converting enzyme inhibitors (ACEIs) have shown promising results in decreasing the incidence and the severity of ischemic stroke in populations at risk and in improving ischemic stroke outcomes.
  10. Hassan Y, Aziz NA, Al-Jabi SW, Looi I, Zyoud SH
    J Cardiovasc Pharmacol Ther, 2010 Sep;15(3):282-8.
    PMID: 20472813 DOI: 10.1177/1074248410368049
    BACKGROUND: Hypertension and ischemic heart disease (IHD) are among the most prevalent modifiable risk factors for stroke. Clinical trial evidence suggests that antihypertensive medications are recommended for prevention of recurrent ischemic stroke in hypertensive and normotensive patients.
    OBJECTIVES: The objectives of this study were to analyze and evaluate the utilization of antihypertensive medication for acute ischemic stroke (AIS) or transient ischemic attack (TIA) survivors in relation to recent recommendations and guidelines and to compare their use among patients with or without IHD.
    METHODS: This was a retrospective cohort study of all patients with AIS/TIA attending the hospital from July 1, 2008 to December 31, 2008. Demographic data, clinical characteristics, different classes of antihypertensive medications, and different antihypertensive combinations prescribed to AIS/TIA survivors were analyzed among patients with and without IHD. Statistical Package for Social Sciences (SPSS) program version 15 was used for data analysis.
    RESULTS: In all, 383 AIS/TIA survivors were studied, of which 66 (19.5%) had a documented history of IHD. Three quarters (n = 260; 76.9%) of AIS or TIA survivors received antihypertensive medication, mostly as monotherapy, at discharge. The majority of patients (n = 201, 59.5%) were prescribed angiotensin-converting enzyme inhibitors (ACEIs). Patients with IHD were significantly prescribed more β-blockers than patients without IHD (P = .003). A history of hypertension, a history of diabetes mellitus, and age were significantly associated with prescription of antihypertensive medications at discharge (P < .001, P < .001, and P < .001, respectively).
    CONCLUSION: Patterns of antihypertensive therapy were commonly but not adequately consistent with international guidelines. Screening stroke survivors for blood pressure control, initiating appropriate antihypertensive medications, and decreasing the number of untreated patients might help reduce the risk of recurrent strokes and increase survival.
  11. Low DW, Looi I, Manocha AB, Ang HA, Nagalingam M, Ayop NA, et al.
    Med J Malaysia, 2012 Oct;67(5):538-9.
    PMID: 23770879 MyJurnal
    A report of a patient with Lazarus phenomenon (the return of spontaneous circulation after cardiopulmonary resuscitation) following cardiac arrest (myocardium ischemia) is presented. A 65 year patient was found unconscious at home. He taken to the emergency department On arrival he was unconscious, his pupils fixed and dilated bilaterally. Resuscitation proceeded for 55 minutes. He was then pronounced dead. Forty minutes later spontaneous breathing was noted and his blood pressure was 110/48 and heart rate 90bpm. He survived a further 13 days in the coronary care unit. The implications for management of cardiac arrest in the emergency and medical department are discussed.
  12. Loh HC, Lim R, Lee KW, Ooi CY, Chuan DR, Looi I, et al.
    Stroke Vasc Neurol, 2021 Mar;6(1):109-120.
    PMID: 33109618 DOI: 10.1136/svn-2020-000519
    There are several previous studies on the association of vitamin E with prevention of stroke but the findings remain controversial. We have conducted a systematic review, meta-analysis together with trial sequential analysis of randomised controlled trials to evaluate the effect of vitamin E supplementation versus placebo/no vitamin E on the risk reduction of total, fatal, non-fatal, haemorrhagic and ischaemic stroke. Relevant studies were identified by searching online databases through Medline, PubMed and Cochrane Central Register of Controlled Trials. A total of 18 studies with 148 016 participants were included in the analysis. There was no significant difference in the prevention of total stroke (RR (relative risk)=0.98, 95% CI 0.92-1.04, p=0.57), fatal stroke (RR=0.96, 95% CI 0.77-1.20, p=0.73) and non-fatal stroke (RR=0.96, 95% CI 0.88-1.05, p=0.35). Subgroup analyses were performed under each category (total stroke, fatal stroke and non-fatal stroke) and included the following subgroups (types of prevention, source and dosage of vitamin E and vitamin E alone vs control). The findings in all subgroup analyses were statistically insignificant. In stroke subtypes analysis, vitamin E showed significant risk reduction in ischaemic stroke (RR=0.92, 95% CI 0.85-0.99, p=0.04) but not in haemorrhagic stroke (RR=1.17, 95% CI 0.98-1.39, p=0.08). However, the trial sequential analysis demonstrated that more studies were needed to control random errors. Limitations of this study include the following: trials design may not have provided sufficient power to detect a change in stroke outcomes, participants may have had different lifestyles or health issues, there were a limited number of studies available for subgroup analysis, studies were mostly done in developed countries, and the total sample size for all included studies was insufficient to obtain a meaningful result from meta-analysis. In conclusion, there is still a lack of statistically significant evidence of the effects of vitamin E on the risk reduction of stroke. Nevertheless, vitamin E may offer some benefits in the prevention of ischaemic stroke and additional well-designed randomised controlled trials are needed to arrive at a definitive finding. PROSPERO registration number: CRD42020167827.
  13. Loh HC, Neoh KK, Tang ASN, Chin CJ, Suppiah PD, Looi I, et al.
    Medicina (Kaunas), 2021 May 19;57(5).
    PMID: 34069433 DOI: 10.3390/medicina57050507
    Background and Objectives: The Coronavirus disease 2019 (COVID-19) pandemic caused significant disruption to established medical care systems globally. Thus, this study was aimed to compare the admission and outcome variables such as number of patient and its severity, acute recanalisation therapy given pre-post COVID-19 at a primary stroke centre located in Malaysia. Methods: This cross-sectional hospital-based study included adult ischaemic stroke patients. Variables of the study included the number of ischaemic stroke patients, the proportions of recanalisation therapies, stroke severity during admission based on the National Institutes of Health Stroke Scale, functional outcome at discharge based on the modified Rankin Scale, and relevant workflow metrics. We compared the outcome between two six-month periods, namely the pre-COVID-19 period (March 2019 to September 2019) and the COVID-19 period (March 2020 to September 2020). Results: There were 131 and 156 patients, respectively, from the pre-COVID-19 period and the COVID-19 period. The median door-to-scan time and the median door-to-reperfusion time were both significantly shorter in the COVID-19 period (24.5 min versus 12.0 min, p = 0.047) and (93.5 min versus 60.0 min, p = 0.015), respectively. There were also significantly more patients who received intravenous thrombolysis (7.6% versus 17.3%, p = 0.015) and mechanical thrombectomy (0.8% versus 6.4%, p = 0.013) in the COVID-19 period, respectively. Conclusions: The COVID-19 pandemic may not have caused disruptions of acute stroke care in our primary stroke centre. Our data indicated that the number of ischaemic stroke events remained stable, with a significant increase of recanalisation therapies and better in-hospital workflow metrics during the COVID-19 pandemic period. However, we would like to highlight that the burden of COVID-19 cases in the study area was very low. Therefore, the study may not have captured the true burden (and relevant delays in stroke patient management) during the COVID-19 pandemic. The effect of the pandemic crisis is ongoing and both pre-hospital and in-hospital care systems must continue to provide optimal, highly time-dependent stroke care services.
  14. Albart SA, Yusof Khan AHK, Abdul Rashid A, Wan Zaidi WA, Bidin MZ, Looi I, et al.
    PeerJ, 2022;10:e13310.
    PMID: 35469195 DOI: 10.7717/peerj.13310
    BACKGROUND: Despite rapid advances in acute ischaemic stroke (AIS) management, many healthcare professionals (HCPs) might not be aware of the latest recommended management of AIS patients. Therefore, we aimed to determine the level and factors associated with AIS management knowledge among Malaysian HCPs.

    METHODS: This cross-sectional online questionnaire study was conducted nationwide among 627 HCPs in Malaysia using the Acute Stroke Management Questionnaire (ASMaQ). Multiple logistic regression was used to predict the relationship between the independent variables (age, gender, years of service, profession, work setting, work sector, seeing stroke patients in daily practice, and working with specialists) and the outcome variable (good vs poor knowledge).

    RESULTS: Approximately 76% (95% CI [73-79%]) of HCPs had good overall knowledge of stroke. The highest proportion of HCPs with good knowledge was noted for General Stroke Knowledge (GSK) [88.5% (95% CI [86-91%])], followed by Advanced Stroke Management (ASM) [61.2% (95% CI [57-65%])] and Hyperacute Stroke Management (HSM) [58.1% (95% CI [54-62%])]. The odds of having poor knowledge of stroke were significantly higher among non-doctor HCPs [adjusted OR = 3.46 (95% CI [1.49-8.03]), P = 0.004]; among those not seeing stroke patients in daily practice [adjusted OR = 2.67 (95% CI [1.73-4.10]), P < 0.001]; and among those working without specialists [adjusted OR = 2.41 (95% CI [1.38-4.18]), P = 0.002].

    CONCLUSIONS: Stroke education should be prioritised for HCPs with limited experience and guidance. All HCPs need to be up-to-date on the latest AIS management and be able to make a prompt referral to an appropriate facility. Therefore, more stroke patients will benefit from advanced stroke care.

  15. Hameed S, Fuh JL, Senanarong V, Ebenezer EGM, Looi I, Dominguez JC, et al.
    J Alzheimers Dis Rep, 2020 Feb 12;4(1):21-37.
    PMID: 32206755 DOI: 10.3233/ADR-190143
    Clinical diagnosis of Alzheimer's disease (AD) is based on symptoms; however, the challenge is to diagnose AD at the preclinical stage with the application of biomarkers and initiate early treatment (still not widely available). Currently, cerebrospinal fluid (CSF) amyloid-β 42 (Aβ42) and tau are used in the clinical diagnosis of AD; nevertheless, blood biomarkers (Aβ42 and tau) are less predictive. Amyloid-positron emission tomography (PET) imaging is an advancement in technology that uses approved radioactive diagnostic agents (florbetapir, flutemetamol, or florbetaben) to estimate Aβ neuritic plaque density in adults with cognitive impairment evaluated for AD and other causes of cognitive decline. There is no cure for AD to date-the disease progression cannot be stopped or reversed; approved pharmacological agents (donepezil, galantamine, and rivastigmine; memantine) provide symptomatic treatment. However, the disease-modifying therapies are promising; aducanumab and CAD106 are in phase III trials for the early stages of AD. In conclusion, core CSF biomarkers reflect pathophysiology of AD in the early and late stages; the application of approved radiotracers have potential in amyloid-PET brain imaging to detect early AD.
  16. Elhefnawy ME, Sheikh Ghadzi SM, Albitar O, Tangiisuran B, Zainal H, Looi I, et al.
    Front Neurol, 2023;14:1118711.
    PMID: 37188311 DOI: 10.3389/fneur.2023.1118711
    BACKGROUND: There are established correlations between risk factors and ischemic stroke (IS) recurrence; however, does the hazard of recurrent IS change over time? What is the predicted baseline hazard of recurrent IS if there is no influence of variable predictors? This study aimed to quantify the hazard of recurrent IS when the variable predictors were set to zero and quantify the secondary prevention influence on the hazard of recurrent ischemic stroke.

    METHODS: In the population cohort involved in this study, data were extracted from 7,697 patients with a history of first IS attack registered with the National Neurology Registry of Malaysia from 2009 to 2016. A time-to-recurrent IS model was developed using NONMEM version 7.5. Three baseline hazard models were fitted into the data. The best model was selected using maximum likelihood estimation, clinical plausibility, and visual predictive checks.

    RESULTS: Within the maximum 7.37 years of follow-up, 333 (4.32%) patients had at least one incident of recurrent IS. The data were well described by the Gompertz hazard model. Within the first 6 months after the index IS, the hazard of recurrent IS was predicted to be 0.238, and 6 months after the index attack, it reduced to 0.001. The presence of typical risk factors such as hyperlipidemia [HR, 2.22 (95%CI: 1.81-2.72)], hypertension [HR, 2.03 (95%CI: 1.52-2.71)], and ischemic heart disease [HR, 2.10 (95%CI: 1.64-2.69)] accelerated the hazard of recurrent IS, but receiving antiplatelets (APLTs) upon stroke decreased this hazard [HR, 0.59 (95%CI: 0.79-0.44)].

    CONCLUSION: The hazard of recurrent IS magnitude differs during different time intervals based on the concomitant risk factors and secondary prevention.

  17. Elhefnawy M, Noor Harun S, Leykhim T, Tangiisuran B, Zainal H, Looi I, et al.
    Cureus, 2023 Dec;15(12):e50794.
    PMID: 38239519 DOI: 10.7759/cureus.50794
    Objectives Compared with the first stroke, neurological impairment caused by stroke recurrence is more serious, more difficult to treat, and has a higher mortality rate, especially among ischemic stroke (IS) patients with diabetes mellitus (DM). Although there are established correlations between factors and IS recurrence, there were some issues regarding the naive hazard of IS recurrence with no risk factor influence, and how does the baseline hazard differ among patients with DM and non-DM? To answer all these questions, two time-to-event (TTE) models of recurrent IS after the index IS were developed among IS patients with DM and non-DM. Method A total of 7697 patients with an index IS attack were extracted from the Malaysian Registry of Neurology and stratified according to DM status. Several parametric survival models were evaluated using nonlinear mixed-effect modeling software (NONMEM 7.5). The final model was determined according to the lowest objective function value, graphical evaluation, numerical diagnostics, and clinical plausibility. Additionally, the final model was validated internally and temporally using Kaplan-Meier visual predictive checks (KM-VPCs). Results One hundred ninety-five (5.82%) of 3493 DM patients and 138 (3.28%) of 4204 non-DM patients developed a recurrent IS with a maximum follow-up of 7.37 years. Gompertz's model best fitted the data. With no influence on risk factors, the index IS attack was predicted to contribute to the hazard of recurrent IS by 0.356 and 0.253 within the first six months after the index IS among patients with and without DM, respectively. Even after six months of index IS, the recurrent IS baseline hazard was not equal to zero among both groups (0.0023, 0.0018). Moreover, after incorporating the time and risk factors, the recurrent hazards increased exponentially during the first three years after the index IS followed by an exponential reduction afterward. The recurrent IS predictors among DM patients were ischemic heart disease (IHD) and hyperlipidemia (HPLD). IHD and HPLD increased the hazard of recurrent IS by 2.40 and 1.88 times, respectively, compared to those without IHD and HPLD before index IS (HR, 2.40 (1.79-3.20)), and (HR, 1.88 (1.44-2.45)) respectively. Conclusion The baseline hazard was the highest during the first six months after the index IS. Moreover, receiving medications for secondary prevention failed to demonstrate a significant association with reducing IS recurrence among IS patients with DM, suggesting a need for more intensive patient screening and new strategies for secondary prevention among IS patients with DM.
  18. Albitar O, Harun SN, Abidin NE, Tangiisuran B, Zainal H, Looi I, et al.
    J Stroke Cerebrovasc Dis, 2020 Oct;29(10):105173.
    PMID: 32912507 DOI: 10.1016/j.jstrokecerebrovasdis.2020.105173
    BACKGROUND: Diabetes and obesity are established risk factors for stroke. The current study aimed to assess risk factors of ischemic stroke recurrence in diabetic patients based on their body mass index (BMI).

    METHODS: A total of 4005 diabetic patients who had a history of ischemic stroke were identified in a retrospective cross-sectional dataset from the Malaysian National Neurology Registry. Patients were classified based on BMI, and multivariable regression analysis was used to evaluate the association between risk factors and recurrent ischemic stroke.

    RESULTS: Among obese patients, those with ischemic heart disease (aOR, 1.873; 95% CI, 1.131-3.103), received formal education (aOR, 2.236; 95% CI, 1.306-3.830), and received anti-diabetic medication (aOR, 1.788; 95% CI, 1.180-2.708) had a higher stroke recurrence risk, while receiving angiotensin receptors blockers (aOR, 0.261; 95% CI, 0.126-0.543) lowered the odds of recurrence. Overweight patients with hypertension (aOR, 1.011; 95% CI, 1.002-1.019) for over 10 years (aOR, 3.385; 95% CI, 1.088-10.532) and diabetes prior to the first stroke (aOR, 1.823; 95% CI, 1.020-3.259) as well as those received formal education (aOR, 2.403; 95% CI, 1.126-5.129) had higher odds of stroke recurrence, while receiving angiotensin-converting enzyme inhibitors (aOR, 0.244; 95% CI, 0.111-0.538) lowered the recurrence risk. Normal weight East Malaysians (aOR, 0.351; 95% CI, 0.164-0.750) receiving beta-blockers (aOR, 0.410; 95% CI, 0.174-0.966) had lower odds of stroke recurrence.

    CONCLUSIONS: Ischemic heart disease, hypertension, receiving anti-hypertensive agents, and educational level were independent predictors of recurrent stroke in obese patients. Managing the modifiable risk factors can decrease the odds of stroke recurrence.

  19. Ganasegeran K, Hor CP, Jamil MFA, Loh HC, Noor JM, Hamid NA, et al.
    PMID: 32784771 DOI: 10.3390/ijerph17165723
    Diabetes causes significant disabilities, reduced quality of life and mortality that imposes huge economic burden on societies and governments worldwide. Malaysia suffers a high diabetes burden in Asia, but the magnitude of healthcare expenditures documented to aid national health policy decision-making is limited. This systematic review aimed to document the economic burden of diabetes in Malaysia, and identify the factors associated with cost burden and the methods used to evaluate costs. Studies conducted between 2000 and 2019 were retrieved using three international databases (PubMed, Scopus, EMBASE) and one local database (MyCite), as well as manual searches. Peer reviewed research articles in English and Malay on economic evaluations of adult type 2 diabetes conducted in Malaysia were included. The review was registered with PROSPERO (CRD42020151857), reported according to PRISMA and used a quality checklist adapted for cost of illness studies. Data were extracted using a data extraction sheet that included study characteristics, total costs, different costing methods and a scoring system to assess the quality of studies reviewed. The review identified twelve eligible studies that conducted cost evaluations of type 2 diabetes in Malaysia. Variation exists in the costs and methods used in these studies. For direct costs, four studies evaluated costs related to complications and drugs, and two studies were related to outpatient and inpatient costs each. Indirect and intangible costs were estimated in one study. Four studies estimated capital and recurrent costs. The estimated total annual cost of diabetes in Malaysia was approximately USD 600 million. Age, type of hospitals or health provider, length of inpatient stay and frequency of outpatient visits were significantly associated with costs. The most frequent epidemiological approach employed was prevalence-based (n = 10), while cost analysis was the most common costing approach used. The current review offers the first documented evidence on cost estimates of diabetes in Malaysia.
  20. Aziz S, Sheikh Ghadzi SM, Abidin NE, Tangiisuran B, Zainal H, Looi I, et al.
    J Diabetes Res, 2019;2019:1794267.
    PMID: 31886276 DOI: 10.1155/2019/1794267
    Background and Purpose: Diabetes mellitus has been reported as a strong independent risk factor for stroke recurrence. Data on the modifiable factors contributing to the recurrence of stroke in type 2 diabetic Malaysian population with a history of stroke stratified by genders are lacking, and this supports the importance of this study.

    Method: The data of 4622 patients with T2DM who had a history of stroke was obtained from the Malaysian National Stroke Registry. Univariate analysis was performed to differentiate between genders with and without stroke recurrence in terms of demographics, first stroke attack presentations, and other clinical characteristics. The significant factors determined from the univariate analysis were further investigated using logistic regression.

    Results: Ischemic heart diseases were found significantly associated with the stroke recurrence in males (OR = 1.738; 95% CI: 1.071-2.818) as well as female (OR = 5.859; 95% CI: 2.469-13.752) diabetic patients. The duration of hypertension, as well as the duration of diabetes, has been associated with the recurrence in both male and female subjects (p value < 0.05). Smoking status has an impact on the stroke recurrence in male subjects, while no significant association was observed among their peers.

    Conclusions: Most of the predictive factors contributing to the recurrence of stroke in type 2 diabetic Malaysian population with a history of stroke are modifiable, in which IHD was the most prominent risk factor in both genders. The impact of optimizing the management of IHD as well as blood glucose control on stroke recurrence may need to be elucidated. No major differences in recurrent stroke predictors were seen between genders among the Malaysian population with type 2 diabetes mellitus who had a previous history of stroke.

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