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  1. Hwong WY, Bots ML, Selvarajah S, Kappelle LJ, Abdul Aziz Z, Sidek NN, et al.
    PLoS One, 2016;11(10):e0165330.
    PMID: 27768752 DOI: 10.1371/journal.pone.0165330
    A shortage of computed tomographic (CT) machines in low and middle income countries often results in delayed CT imaging for patients suspected of a stroke. Yet, time constraint is one of the most important aspects for patients with an ischemic stroke to benefit from thrombolytic therapy. We set out to assess whether application of the Siriraj Stroke Score is able to assist physicians in prioritizing patients with a high probability of having an ischemic stroke for urgent CT imaging.
  2. Ang SH, Hwong WY, Bots ML, Sivasampu S, Abdul Aziz AF, Hoo FK, et al.
    PLoS One, 2021;16(1):e0245448.
    PMID: 33465103 DOI: 10.1371/journal.pone.0245448
    BACKGROUND AND OBJECTIVES: Risk of readmissions is an important quality indicator for stroke care. Such information is limited among low- and middle-income countries. We assessed the trends for 28-day readmissions after a stroke in Malaysia from 2008 to 2015 and evaluated the causes and factors associated with readmissions in 2015.

    METHODS: Using the national hospital admission records database, we included all stroke patients who were discharged alive between 2008 and 2015 for this secondary data analysis. The risk of readmissions was described in proportion and trends. Reasons were coded according to the International Classification of Diseases, 10th Edition. Multivariable logistic regression was performed to identify factors associated with readmissions.

    RESULTS: Among 151729 patients, 11 to 13% were readmitted within 28 days post-discharge from their stroke events each year. The trend was constant for ischemic stroke but decreasing for hemorrhagic stroke. The leading causes for readmissions were recurrent stroke (32.1%), pneumonia (13.0%) and sepsis (4.8%). The risk of 28-day readmission was higher among those with stroke of hemorrhagic (adjusted odds ratio (AOR): 1.52) and subarachnoid hemorrhage (AOR: 2.56) subtypes, and length of index admission >3 days (AOR: 1.48), but lower among younger age groups of 35-64 (AORs: 0.61-0.75), p values <0.001.

    CONCLUSION: The risk of 28-day readmission remained constant from 2008 to 2015, where one in eight stroke patients required readmission, mainly attributable to preventable causes. Age, ethnicity, stroke subtypes and duration of the index admission influenced the risk of readmission. Efforts should focus on minimizing potentially preventable admissions, especially among those at higher risk.

  3. Hwong WY, Bots ML, Selvarajah S, Abdul Aziz Z, Sidek NN, Spiering W, et al.
    PLoS One, 2016;11(11):e0166524.
    PMID: 27846309 DOI: 10.1371/journal.pone.0166524
    BACKGROUND: The increase in angiotensin II (Ang II) formation by selected antihypertensive drugs is said to exhibit neuroprotective properties, but this translation into improvement in clinical outcomes has been inconclusive. We undertook a study to investigate the relationship between types of antihypertensive drugs used prior to a stroke event and ischemic stroke severity. We hypothesized that use of antihypertensive drugs that increase Ang II formation (Ang II increasers) would reduce ischemic stroke severity when compared to antihypertensive drugs that suppress Ang II formation (Ang II suppressors).

    METHODS: From the Malaysian National Neurology Registry, we included hypertensive patients with first ischemic stroke who presented within 48 hours from ictus. Antihypertensive drugs were divided into Ang II increasers (angiotensin-I receptor blockers (ARBs), calcium channel blockers (CCBs) and diuretics) and Ang II suppressors (angiotensin-converting-enzyme inhibitors (ACEIs) and beta blockers). We evaluated stroke severity during admission with the National Institute of Health Stroke Scale (NIHSS). We performed a multivariable logistic regression with the score being dichotomized at 15. Scores of less than 15 were categorized as less severe stroke.

    RESULTS: A total of 710 patients were included. ACEIs was the most commonly prescribed antihypertensive drug in patients using Ang II suppressors (74%) and CCBs, in patients prescribed with Ang II increasers at 77%. There was no significant difference in the severity of ischemic stroke between patients who were using Ang II increasers in comparison to patients with Ang II suppressors (OR: 1.32, 95%CI: 0.83-2.10, p = 0.24).

    CONCLUSION: In our study, we found that use of antihypertensive drugs that increase Ang II formation was not associated with less severe ischemic stroke as compared to use of antihypertensive drugs that suppress Ang II formation.

  4. Hwong WY, Bots ML, Selvarajah S, Sivasampu S, Reidpath DD, Law WC, et al.
    Int J Stroke, 2019 10;14(8):826-834.
    PMID: 30843480 DOI: 10.1177/1747493019832995
    BACKGROUND: Sex differences in cardiovascular diseases generally disadvantage women, particularly within developing regions.

    AIMS: This study aims to examine sex-related differences in stroke metrics across Southeast Asia in 2015. Furthermore, relative changes between sexes are compared from 1990 to 2015.

    METHODS: Data were sourced from the Global Burden of Disease Study. Incidence and mortality from ischemic and hemorrhagic strokes were explored with the following statistics derived: (1) women-to-men incidence/mortality ratio and (2) relative percentage change in rate.

    RESULTS: Women had lower incidence and mortality from stroke compared to men. Notable findings include higher ischemic stroke incidence for women at 30-34 years in high-income countries (women-to-men ratio: 1.3, 95% CI: 0.1, 16.2 in Brunei and 1.3, 95% CI: 0.5, 3.2 in Singapore) and the largest difference between sexes for ischemic stroke mortality in Vietnam and Myanmar across most ages. Within the last 25 years, greater reductions for ischemic stroke metrics were observed among women compared to men. Nevertheless, women below 40 years in some countries showed an increase in ischemic stroke incidence between 0.5% and 11.4%, whereas in men, a decline from -4.2% to -44.2%. Indonesia reported the largest difference between sexes for ischemic stroke mortality; a reduction for women whereas an increase in men. For hemorrhagic stroke, findings were similar: higher incidence among young women in high-income countries and greater reductions for stroke metrics in women than men over the last 25 years.

    CONCLUSIONS: Distinct sex-specific differences observed across Southeast Asia should be accounted in future stroke preventive guidelines.

  5. Hwong WY, Ang SH, Bots ML, Sivasampu S, Selvarajah S, Law WC, et al.
    Glob Heart, 2021 05 26;16(1):39.
    PMID: 34211825 DOI: 10.5334/gh.791
    Background: Data on nationwide trends for stroke metrics are crucial to understand the extent of the disease burden to a country's health system. Yet, this information remains scarce in low- and middle-income countries.

    Objectives: This study investigated trends of stroke incidence and 28-day all-cause mortality after a stroke from 2008 to 2016 in Malaysia, through linkage across national data sources.

    Methods: Hospital admissions with a principal diagnosis of stroke or transient ischemic attack were included. Cases with first stroke were identified through linkage of hospital admission registers where age and sex-standardized trends of stroke incidence and its subtypes were calculated. By linking hospital registers to the National Death Register, the 28-day all-cause mortality rates after a stroke were estimated. Mann-Kendall's test was used for trend evaluation.

    Results: From 243,765 records, the trend of stroke incidence showed an increase of 4.9% in men and a drop of 3.8% among women. Incidences were higher in men, at 99.1 per 100,000 population in 2008 and 103.9 per 100,000 in 2016 than women (80.3 per 100,000 in 2008 and 77.2 per 100,000 in 2016). There was a substantial increase in stroke incidence among those below 65 years old, with the largest increase of 53.3% in men aged between 35-39 years and 50.4% in women of similar age group. The trend for 28-day all-cause mortality showed a decline for men at -13.1% and women, -10.6%. Women had higher mortality from stroke (22.0% in 2008 and 19.7% in 2016) than men (19.4% in 2008 to 17.2% in 2016).

    Conclusion: This first empirical study on stroke trends in Malaysia revealed a worrying increase in stroke incidence among the younger population. Despite a declining trend, mortality rates remained moderately high especially in women. Comprehensive strategies to strengthen the prevention and management of stroke care are warranted.

  6. Hwong WY, Abdul Aziz Z, Sidek NN, Bots ML, Selvarajah S, Kappelle LJ, et al.
    BMC Neurol, 2017 Nov 23;17(1):203.
    PMID: 29169331 DOI: 10.1186/s12883-017-0984-1
    BACKGROUND: Evaluation of secondary stroke prevention in low and middle-income countries remains limited. This study assessed the prescription of secondary preventive drugs among ischemic stroke patients upon hospital discharge in Malaysia and identified factors related to the prescribing decisions.

    METHODS: From Malaysian National Stroke Registry, we included patients with non-fatal ischemic stroke. Prescriptions of antiplatelet, anticoagulants, antihypertensive drugs and lipid-lowering drugs were assessed. Multi-level logistic regressions were performed to determine the relation between potential factors and drug prescriptions.

    RESULTS: Of 5292 patients, 48% received antihypertensive drugs, 88.9% antiplatelet and 88.7% lipid-lowering drugs upon discharge. Thirty-three percent of patients with an indication for anticoagulants (n = 391) received it. Compared to patients <=50 years, patients above 70 years were less likely to receive antiplatelet (OR: 0.72, 95% CI: 0.50-1.03), lipid-lowering drugs (OR: 0.66, 95% CI: 0.45-0.95) and anticoagulants (OR: 0.27, 95% CI: 0.09-0.83). Patients with moderate to severe disability upon discharge had less odds of receiving secondary preventive drugs; an odds ratio of 0.57 (95% CI: 0.45-0.71) for antiplatelet, 0.86 (95% CI: 0.75-0.98) for antihypertensive drugs and 0.78 (95% CI: 0.63-0.97) for lipid-lowering drugs in comparison to those with minor disability. Having prior specific comorbidities and drug prescriptions significantly increased the odds of receiving these drugs. No differences were found between sexes and ethnicities.

    CONCLUSIONS: Prescription of antihypertensive drugs and anticoagulants among ischemic stroke patients in Malaysia were suboptimal. Efforts to initiate regular clinical audits to evaluate the uptake and effectiveness of secondary preventive strategies are timely in low and middle-income settings.

  7. Lim YMF, Molnar M, Vaartjes I, Savarese G, Eijkemans MJC, Uijl A, et al.
    Eur Heart J Qual Care Clin Outcomes, 2022 10 26;8(7):761-769.
    PMID: 34596659 DOI: 10.1093/ehjqcco/qcab070
    BACKGROUND: Heart failure (HF) trials have stringent inclusion and exclusion criteria, but limited data exist regarding generalizability of trials. We compared patient characteristics and outcomes between patients with HF and reduced ejection fraction (HFrEF) in trials and observational registries.

    METHODS AND RESULTS: Individual patient data for 16 922 patients from five randomized clinical trials and 46 914 patients from two HF registries were included. The registry patients were categorized into trial-eligible and non-eligible groups using the most commonly used inclusion and exclusion criteria. A total of 26 104 (56%) registry patients fulfilled the eligibility criteria. Unadjusted all-cause mortality rates at 1 year were lowest in the trial population (7%), followed by trial-eligible patients (12%) and trial-non-eligible registry patients (26%). After adjustment for age and sex, all-cause mortality rates were similar between trial participants and trial-eligible registry patients [standardized mortality ratio (SMR) 0.97; 95% confidence interval (CI) 0.92-1.03] but cardiovascular mortality was higher in trial participants (SMR 1.19; 1.12-1.27). After full case-mix adjustment, the SMR for cardiovascular mortality remained higher in the trials at 1.28 (1.20-1.37) compared to RCT-eligible registry patients.

    CONCLUSION: In contemporary HF registries, over half of HFrEF patients would have been eligible for trial enrolment. Crude clinical event rates were lower in the trials, but, after adjustment for case-mix, trial participants had similar rates of survival as registries. Despite this, they had about 30% higher cardiovascular mortality rates. Age and sex were the main drivers of differences in clinical outcomes between HF trials and observational HF registries.

  8. Schroeder M, Lim YMF, Savarese G, Suzart-Woischnik K, Baudier C, Dyszynski T, et al.
    Eur J Heart Fail, 2023 Jun;25(6):912-921.
    PMID: 37101398 DOI: 10.1002/ejhf.2868
    AIMS: In order to understand how sex differences impact the generalizability of randomized clinical trials (RCTs) in patients with heart failure (HF) and reduced ejection fraction (HFrEF), we sought to compare clinical characteristics and clinical outcomes between RCTs and HF observational registries stratified by sex.

    METHODS AND RESULTS: Data from two HF registries and five HFrEF RCTs were used to create three subpopulations: one RCT population (n = 16 917; 21.7% females), registry patients eligible for RCT inclusion (n = 26 104; 31.8% females), and registry patients ineligible for RCT inclusion (n = 20 810; 30.2% females). Clinical endpoints included all-cause mortality, cardiovascular mortality, and first HF hospitalization at 1 year. Males and females were equally eligible for trial enrolment (56.9% of females and 55.1% of males in the registries). One-year mortality rates were 5.6%, 14.0%, and 28.6% for females and 6.9%, 10.7%, and 24.6% for males in the RCT, RCT-eligible, and RCT-ineligible groups, respectively. After adjusting for 11 HF prognostic variables, RCT females showed higher survival compared to RCT-eligible females (standardized mortality ratio [SMR] 0.72; 95% confidence interval [CI] 0.62-0.83), while RCT males showed higher adjusted mortality rates compared to RCT-eligible males (SMR 1.16; 95% CI 1.09-1.24). Similar results were also found for cardiovascular mortality (SMR 0.89; 95% CI 0.76-1.03 for females, SMR 1.43; 95% CI 1.33-1.53 for males).

    CONCLUSION: Generalizability of HFrEF RCTs differed substantially between the sexes, with females having lower trial participation and female trial participants having lower mortality rates compared to similar females in the registries, while males had higher than expected cardiovascular mortality rates in RCTs compared to similar males in registries.

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