Survivability of patients admitted for stroke in a primary stroke center, Penang, Malaysia: a retrospective 5-year study.

BACKGROUND: Stroke is one of the most common noncommunicable diseases, with significant public health implications both globally and in Malaysia. The aim of this study was to evaluate post-stroke survivability as well as the major drug classes prescribed for hospitalized stroke patients. METHODS: A 5-year retrospective study was carried out on the survival of stroke patients admitted to Hospital Seberang Jaya, a main stroke center in the state of Penang, Malaysia. Patients admitted for stroke were first identified using the local stroke registry database, and their medical records were then accessed for data collection, which included demographic information, comorbid conditions, and medications prescribed during admission. RESULTS: The Kaplan-Meier overall survivability analysis performed indicated 50.5% survival for the duration of 10 days (p < 0.001) post-stroke. Ten-day survivability differences (p < 0.05) were observed for the categories of type of stroke (ischemic stroke (60.9%) and hemorrhagic stroke (14.1%)); stroke episodes (first (61.1%) and recurrent (39.6%)); anti-platelets (prescribed (46.2%) and not prescribed (41.5%)); statins (prescribed (68.7%) and not prescribed (28.1%)); anti-hypertensive (prescribed (65.4%) and not prescribed (45.9%)); and anti-infectives (prescribed (42.5%) and not prescribed (59.6%)) respectively. Higher risks of mortality were observed among patients with hemorrhagic stroke (HR: 10.61, p = 0.004); with 3 or more comorbidities (HR:6.60, p = 0.020); and not prescribed with statins and anti-diabetic. Patients prescribed anti-infectives, on the other hand, had a higher risk of mortality when compared to patients who did not receive anti-infectives (HR: 13.10, p = 0.019). The major drug classes prescribed for stroke patients were antiplatelet drugs (86.7%), statins (84.4%), and protein pump inhibitors (75.6%). CONCLUSION: The findings of the study are intended to encourage more non-stroke hospitals in Malaysia to increase their efforts in treating stroke patients, as early treatment can help reduce the severity of the stroke. With the incorporation of evidence-based data, this study also contributes to local data for comparison and improves the implementation of regularly prescribed stroke medication.

Clinical outcomes of acute stroke thrombolysis in neurologist and non-neurologist centres – A comparative study in Malaysia

@#Acute ischaemic stroke (AIS) is a devastating disease and one of the leading causes of disabilities worldwide. From 2010 to 2014, the incidence of stroke in Malaysia had increased from 65 to 187 per 100,000 population.1 Thrombolytic therapy with intravenous recombinant tissue plasminogen activator (rtPA) within 4.5 hours of symptom onset has been shown to be an effective treatment for AIS. Patients who receive thrombolysis are 30 percent more likely to achieve excellent functional outcome (modified Rankin scale of 0 to 1) at 3 months compared to placebo.2 Unfortunately, the delivery of stroke thrombolysis service in Malaysia is often limited by the availability of neurologists. To date, the ratio of neurologists capable of performing thrombolysis serving in public hospitals to the Malaysian population is 1:1.4 million.3 To counteract this disparity and to cope with the increasing stroke burden in Malaysia, there has been an advocacy for greater involvement of non-neurologists, i.e., general and emergency physicians in performing of stroke thrombolysis.4 Emerging data based on short term outcomes appear to support this notion. Based on a 2015 single center study on 49 AIS patients in Australia, A. Lee et al., reported that there was no significant difference in door to needle time, rates of symptomatic intracranial bleeding (SICH), and mortality between patients thrombolysed by neurologists versus stroke physicians.5 In 2016, a larger multicentre study in Thailand reported that patients thrombolysed in hospitals without neurologists had lower National Institute of Health Stroke Scale (NIHSS) scores at discharge and lower inpatient mortality rate compared to patients treated in neurologist hospitals.6 Based on these short term outcomes, both studies suggest that nonneurologists are able to thrombolyse AIS patients safely and effectively. Data comparing long term functional outcomes in thrombolysis prescribed by neurologists and nonneurologists are still very limited. The primary objective of this study was to evaluate and compare the 3-month functional outcomes of thrombolytic therapy between hospitals with and without on-site neurologists. The secondary objective was to assess the doorto-needle time and complication rates of thrombolysis service in both hospitals

Socio-demographics and clinical characteristics affecting pre-hospital delays in acute stroke patients: A 6-year registry study from a Malaysian stroke hospital

@#Background and objectives: The cumulative time spent without medical intervention in acute stroke patients may affect clinical outcomes. As the onset-to-arrival time to the hospital is crucial for effective treatment interventions, this study aimed to explore the factors associated with pre-hospital delays amongst acute stroke patients. Methods: We explored 932 patients data retrieved from the National Neurology Registry of Seberang Jaya Hospital between January 2013 and December 2018. Data on patient demographics and stroke manifestations were analysed using descriptive, univariate and multivariate logistic regressions. Results: Most patients were men (62.9%) with an average age of 62 years old. In the final multivariate regression model, pre-hospital delay was significantly lower among Chinese patients (aOR=0.6, 95% CI 0.4–0.9, p=0.016) and those using hospital ambulance (aOR=0.4, 95% CI 0.3–0.7, p<0.001), but higher among patients with lacunar infarcts (aOR=2.5, 95% CI 1.4–3.3; p<0.001). Conclusions: Demographic characteristic (ethnicity) and stroke manifestations, particularly stroke subtypes, and mode of transport were mainly associated with pre-hospital delays among acute stroke patients.

Association of NOTCH3 Gene Polymorphisms with Ischemic Stroke and its Subtypes: A Meta-Analysis.

Background and objectives: NOTCH3 gene variations play a significant role in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, the role of NOTCH3 gene polymorphisms in the risk of ischemic stroke, and its subtypes such as atherothrombotic or lacunar strokes, remains unclear. Aims: Hence, we carried out a meta-analysis to examine whether the NOTCH3 rs1043994, rs1044009 and rs3815188 polymorphisms are associated with ischemic stroke and its major subtypes. Materials and Methods: All relevant studies were systematically screened and meta-analyzed using Review Manager (Revman) version 5.3. The strength of the association between NOTCH3 polymorphisms and ischemic stroke risk and its subtypes were measured as odds ratios and 95% confidence intervals, under different genetic models. Results: A total of ten studies were identified, five of which considered NOTCH3 rs1043994 (2077 cases/2147 controls), five of which considered NOTCH3 rs1044009 (2315 cases/3053 controls), and nine of which considered NOTCH3 rs3815188 (2819 cases/2769 controls). These studies were meta-analyzed for their association with ischemic stroke risk. Four studies (874 cases/2002 controls) of the NOTCH3 rs3815188 polymorphism and three studies of the NOTCH3 rs1043994 (643 cases/1552 controls) polymorphism were meta-analyzed for lacunar stroke risk. Three studies (1013 cases/1972 controls) of the NOTCH3 rs3815188 polymorphism were meta-analyzed for atherothrombotic stroke risk. The meta-analysis results showed a lack of association between all of the studied polymorphisms and the risk of ischemic stroke and its major subtypes (i.e., atherothrombotic and lacunar). Conclusions: NOTCH3 polymorphisms are not significantly associated with the risk of ischemic stroke and its subtypes (p < 0.05).

Meta-Analysis of Factor V, Factor VII, Factor XII, and Factor XIII-A Gene Polymorphisms and Ischemic Stroke.

Numerous studies examined the association between factors FV, FVII, FXII, and FXIII-A gene polymorphisms and ischemic stroke, but conclusive evidence is yet to be obtained. Thus, this meta-analysis aimed to investigate the novel association of FV rs1800595, FVII rs5742910, FXII rs1801020, and FXIII-A rs5982 and rs3024477 polymorphisms with ischemic stroke risk. A systematic review was performed on articles retrieved before June 2018. Relevant data were extracted from eligible studies and meta-analyzed using RevMan version 5.3. The strength of association between studied polymorphisms and ischemic stroke risk was calculated as odds ratios and 95% confidence intervals, by applying both fixed- and random-effect models. A total of 25 studies involving 6100 ischemic stroke patients and 9249 healthy controls were incorporated in the final meta-analysis model. Specifically, rs1800595, rs5742910, rs1801020, rs5982, and rs3024477 consisted of 673, 3668, 922, 433, and 404 cases, as well as 995, 4331, 1285, 1321, and 1317 controls, respectively. The pooled analysis indicated that there was no significant association of FV rs1800595, FVII rs5742910, FXII rs1801020, FXIII-A rs5982, and FXIII-A rs3024477 polymorphisms with ischemic stroke risk, under any genetic models (dominant, recessive, over-dominant, and allelic). The present meta-analysis concluded that FV rs1800595, FVII rs5742910, FXII rs1801020, and FXIII-A rs5982 and rs3024477 polymorphisms are not associated with ischemic stroke risk.

Phenytoin toxicity presenting with acute visual loss and acute delirium, a case report

@#Phenytoin is a widely prescribed antiepileptic agent for both focal and generalized seizure. We report a case of a 20-year-old man with focal epilepsy presented with acute bilateral visual loss, and delirium. His random phenytoin serum concentration on admission was 43.6 mg/L, well above the recommended therapeutic range of 10-20 mg/L. Extensive investigations have ruled out other vascular or demyelinating causes. His visual symptoms completely resolved after discontinuing phenytoin for 84 hours. This case shows that acute phenytoin toxicity can result in reversible visual failure.

The impact of APOA5, APOB, APOC3 and ABCA1 gene polymorphisms on ischemic stroke: Evidence from a meta-analysis.

BACKGROUND AND AIMS: Genetic studies have been reported on the association between APOA5, APOB, APOC3 and ABCA1 gene polymorphisms and ischemic stroke, but results remain controversial. Hence, this meta-analysis aimed to infer the causal relationships of APOA5 (rs662799, rs3135506), APOB (rs693, rs1042031, rs1801701), APOC3 (rs4520, rs5128, rs2854116, rs2854117) and ABCA1 rs2230806 with ischemic stroke risk. METHODS: A systematic review was performed for all the articles retrieved from multiple databases, up until March 2017. Data were extracted from all eligible studies, and meta-analysis was carried out using RevMan 5.3 and R package 3.2.1. The strength of association between each studied polymorphism and ischemic stroke risk was measured as odds ratios (ORs) and 95% confidence intervals (CIs), under fixed- and random-effect models. RESULTS: A total of 79 studies reporting on the association between the studied polymorphisms and ischemic stroke risk were identified. The pooled data indicated that all genetic models of APOA5 rs662799 (ORs = 1.23-1.43), allelic and over-dominant models of APOA5 rs3135506 (ORs = 1.77-1.97), APOB rs1801701 (ORs = 1.72-2.13) and APOB rs1042031 (ORs = 1.66-1.88) as well as dominant model of ABCA1 rs2230806 (OR = 1.31) were significantly associated with higher risk of ischemic stroke. However, no significant associations were observed between ischemic stroke and the other five polymorphisms, namely ApoB (rs693) and APOC3 (rs4520, rs5128, rs2854116 and rs2854117), under any genetic model. CONCLUSIONS: The present meta-analysis confirmed a significant association of APOA5 rs662799 CC, APOA5 rs3135506 CG, APOB rs1801701 GA, APOB rs1042031 GA and ABCA1 rs2230806 GG with increased risk of ischemic stroke.

Polymorphisms of MTHFR, eNOS, ACE, AGT, ApoE, PON1, PDE4D, and Ischemic Stroke: Meta-Analysis.

INTRODUCTION: The association between ischemic stroke and genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR; 677C>T and 1298A>C), endothelial nitric oxide synthase (eNOS; -786T>C, +894G>T, and variable number tandem repeat [VNTR]), phosphodiesterase 4D (PDE4D; SNPs 83 and 87), angiotensin-converting enzyme (ACE) I/D, angiotensinogen (AGT) 235M>T, paraoxonase 1 (PON1) 192Q>R, and apolipoprotein E (ApoE) ε2ε3ε4 remains inconclusive. Therefore, this updated meta-analysis aimed to clarify the presumed influence of genetic polymorphisms on ischemic stroke by meta-analyzing the comprehensive coverage of all individual association studies. METHODS: All case-control studies published in different languages such as English, Japanese, Korean, Spanish, Chinese, Hungarian, Ukrainian, or Russian were identified from databases. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated via fixed- and random-effect models. Sensitivity analysis, heterogeneity test, Hardy Weinberg Equilibrium, and Egger's regression analyses were performed in this study. RESULTS: A total of 490 case-control studies with 138,592 cases and 159,314 controls were included in this meta-analysis. Pooled ORs from all the genetic models indicated that MTHFR 677TT and 1298CC, eNOS +894TT and VNTR, PDE4D SNP 83, ACE DD, AGT 235TT, PON1 192RR, and ApoE ε4 polymorphisms were increasing the risks of ischemic stroke. Nevertheless, PDE4D SNP 87 and eNOS -786T>C polymorphisms are not associated with ischemic stroke risks. CONCLUSIONS: Hence, the evidence from this meta-analysis concluded that MTHFR (677C>T and 1298A>C), eNOS (+894G>T and VNTR), PDE4D SNP 83, ACE I/D, AGT 235M>T, PON1 192Q>R, and ApoE ε2ε3ε4 polymorphisms predispose individuals to ischemic stroke.

A Review of Stroke Research in Malaysia from 2000 – 2014

Over 100 articles related to stroke were found in a search through a database dedicated to indexing all literature with original data involving the Malaysian population between years 2000 and 2014. Stroke is emerging as a major public health problem. The development of the National Stroke Registry in the year 2009 aims to coordinate and improve stroke care, as well as to generate more data on various aspects of stroke in the country. Studies on predictors of survival after strokes have shown potential to improve the overall management of stroke, both during acute event and long term care. Stroke units were shown to be effective locally in stroke outcomes and prevention of stroke-related complications. The limited data looking at direct cost of stroke management suggests that the health economic burden in stroke management may be even higher. Innovative rehabilitation programmes including braincomputer interface technology were studied with encouraging results. Studies in traditional complementary medicine for strokes such as acupuncture, Urut Melayu and herbal medicine were still limited.

The Influence of OLR1 and PCSK9 Gene Polymorphisms on Ischemic Stroke: Evidence from a Meta-Analysis.

Both OLR1 and PCSK9 genes are associated with atherosclerosis, cardiovascular disease and ischemic stroke. The overall prevalence of PCSK9 rs505151 and OLR1 rs11053646 variants in ischemic stroke were 0.005 and 0.116, respectively. However, to date, association between these polymorphisms and ischemic stroke remains inconclusive. Therefore, this first meta-analysis was carried out to clarify the presumed influence of these polymorphisms on ischemic stroke. All eligible case-control and cohort studies that met the search terms were retrieved in multiple databases. Demographic and genotyping data were extracted from each study, and the meta-analysis was performed using RevMan 5.3 and Metafor R 3.2.1. The pooled odd ratios (ORs) and 95% confidence intervals (CIs) were calculated using both fixed- and random-effect models. Seven case-control studies encompassing 1897 cases and 2119 controls were critically evaluated. Pooled results from the genetic models indicated that OLR1 rs11053646 dominant (OR = 1.33, 95% CI:1.11-1.58) and co-dominant models (OR = 1.24, 95% CI:1.02-1.51) were significantly associated with ischemic stroke. For the PCSK9 rs505151 polymorphism, the OR of co-dominant model (OR = 1.36, 95% CI:1.01-1.58) was found to be higher among ischemic stroke patients. In conclusion, the current meta-analysis highlighted that variant allele of OLR1 rs11053646 G > C and PCSK9 rs505151 A > G may contribute to the susceptibility risk of ischemic stroke.