1.Factors Influencing Nerinetide Effect on Clinical Outcome in Patients Without Alteplase Treatment in the ESCAPE-NA1 Trial
Mayank GOYAL ; Bijoy K. MENON ; Johanna OSPEL ; Mohammed ALMEKHLAFI ; Charlotte ZERNA ; Raul NOGUEIRA ; Ryan MCTAGGART ; Andrew M. DEMCHUK ; Alexandre Y. POPPE ; Brian BUCK ; Kathy HEARD ; Manish JOSHI ; Diogo HAUSSEN ; Shawna CUTTING ; Shelagh B. COUTTS ; Daniel ROY ; Jeremy L. REMPEL ; Thalia S. FIELD ; Dar DOWLATSHAHI ; Brian van ADEL ; Richard SWARTZ ; Ruchir SHAH ; Eric SAUVAGEAU ; Volker PUETZ ; Frank L. SILVER ; Bruce CAMPBELL ; René CHAPOT ; Michael TYMIANSKI ; Michael D. HILL ;
Journal of Stroke 2025;27(1):95-101
Background:
and Purpose In the ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischaemic Stroke) trial, treatment with nerinetide was associated with improved outcomes in patients who did not receive intravenous alteplase. We compared the effect of nerinetide on clinical outcomes in patients without concurrent intravenous alteplase treatment within different patient subgroups.
Methods:
ESCAPE-NA1 was a multicenter randomized trial in which acute stroke patients with baseline Alberta Stroke Program Early CT Score (ASPECTS) >4 undergoing endovascular treatment (EVT) were randomized to intravenous nerinetide or placebo. The primary outcome was independence (modified Rankin Scale [mRS] score 0–2) at 90 days. We assessed baseline, clinical, and imaging variables as predictors of outcome and for evidence of treatment effect modification. We constructed two multivariable models using variables known prior to randomization and variables known immediately post-EVT procedure to provide adjusted estimates of effect. We assessed for evidence of treatment effect modification using multiplicative interaction terms within each model.
Results:
Four hundred forty-six patients were included in the analysis. Clinical outcomes were better in patients randomized to the nerinetide arm (mRS 0–2: 59.4% vs. 49.8%). There was possible treatment effect modification by ASPECTS score; patients with ASPECTS 8–10 showed a larger treatment effect compared to those with lower ASPECTS score. Younger age, lower NIHSS score, lower baseline serum glucose, absence of atrial fibrillation at baseline, higher ASPECTS score, middle cerebral artery (vs. internal carotid artery) occlusion, use of conscious or no sedation (vs. general anesthesia), and faster treatment were all predictors of favorable outcome.
Conclusion
Patients in the nerinetide arm who were not treated with concurrent alteplase showed improved clinical outcomes and the treatment effect was larger among patients with favorable ASPECTS profiles.
2.Factors Influencing Nerinetide Effect on Clinical Outcome in Patients Without Alteplase Treatment in the ESCAPE-NA1 Trial
Mayank GOYAL ; Bijoy K. MENON ; Johanna OSPEL ; Mohammed ALMEKHLAFI ; Charlotte ZERNA ; Raul NOGUEIRA ; Ryan MCTAGGART ; Andrew M. DEMCHUK ; Alexandre Y. POPPE ; Brian BUCK ; Kathy HEARD ; Manish JOSHI ; Diogo HAUSSEN ; Shawna CUTTING ; Shelagh B. COUTTS ; Daniel ROY ; Jeremy L. REMPEL ; Thalia S. FIELD ; Dar DOWLATSHAHI ; Brian van ADEL ; Richard SWARTZ ; Ruchir SHAH ; Eric SAUVAGEAU ; Volker PUETZ ; Frank L. SILVER ; Bruce CAMPBELL ; René CHAPOT ; Michael TYMIANSKI ; Michael D. HILL ;
Journal of Stroke 2025;27(1):95-101
Background:
and Purpose In the ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischaemic Stroke) trial, treatment with nerinetide was associated with improved outcomes in patients who did not receive intravenous alteplase. We compared the effect of nerinetide on clinical outcomes in patients without concurrent intravenous alteplase treatment within different patient subgroups.
Methods:
ESCAPE-NA1 was a multicenter randomized trial in which acute stroke patients with baseline Alberta Stroke Program Early CT Score (ASPECTS) >4 undergoing endovascular treatment (EVT) were randomized to intravenous nerinetide or placebo. The primary outcome was independence (modified Rankin Scale [mRS] score 0–2) at 90 days. We assessed baseline, clinical, and imaging variables as predictors of outcome and for evidence of treatment effect modification. We constructed two multivariable models using variables known prior to randomization and variables known immediately post-EVT procedure to provide adjusted estimates of effect. We assessed for evidence of treatment effect modification using multiplicative interaction terms within each model.
Results:
Four hundred forty-six patients were included in the analysis. Clinical outcomes were better in patients randomized to the nerinetide arm (mRS 0–2: 59.4% vs. 49.8%). There was possible treatment effect modification by ASPECTS score; patients with ASPECTS 8–10 showed a larger treatment effect compared to those with lower ASPECTS score. Younger age, lower NIHSS score, lower baseline serum glucose, absence of atrial fibrillation at baseline, higher ASPECTS score, middle cerebral artery (vs. internal carotid artery) occlusion, use of conscious or no sedation (vs. general anesthesia), and faster treatment were all predictors of favorable outcome.
Conclusion
Patients in the nerinetide arm who were not treated with concurrent alteplase showed improved clinical outcomes and the treatment effect was larger among patients with favorable ASPECTS profiles.
3.Factors Influencing Nerinetide Effect on Clinical Outcome in Patients Without Alteplase Treatment in the ESCAPE-NA1 Trial
Mayank GOYAL ; Bijoy K. MENON ; Johanna OSPEL ; Mohammed ALMEKHLAFI ; Charlotte ZERNA ; Raul NOGUEIRA ; Ryan MCTAGGART ; Andrew M. DEMCHUK ; Alexandre Y. POPPE ; Brian BUCK ; Kathy HEARD ; Manish JOSHI ; Diogo HAUSSEN ; Shawna CUTTING ; Shelagh B. COUTTS ; Daniel ROY ; Jeremy L. REMPEL ; Thalia S. FIELD ; Dar DOWLATSHAHI ; Brian van ADEL ; Richard SWARTZ ; Ruchir SHAH ; Eric SAUVAGEAU ; Volker PUETZ ; Frank L. SILVER ; Bruce CAMPBELL ; René CHAPOT ; Michael TYMIANSKI ; Michael D. HILL ;
Journal of Stroke 2025;27(1):95-101
Background:
and Purpose In the ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischaemic Stroke) trial, treatment with nerinetide was associated with improved outcomes in patients who did not receive intravenous alteplase. We compared the effect of nerinetide on clinical outcomes in patients without concurrent intravenous alteplase treatment within different patient subgroups.
Methods:
ESCAPE-NA1 was a multicenter randomized trial in which acute stroke patients with baseline Alberta Stroke Program Early CT Score (ASPECTS) >4 undergoing endovascular treatment (EVT) were randomized to intravenous nerinetide or placebo. The primary outcome was independence (modified Rankin Scale [mRS] score 0–2) at 90 days. We assessed baseline, clinical, and imaging variables as predictors of outcome and for evidence of treatment effect modification. We constructed two multivariable models using variables known prior to randomization and variables known immediately post-EVT procedure to provide adjusted estimates of effect. We assessed for evidence of treatment effect modification using multiplicative interaction terms within each model.
Results:
Four hundred forty-six patients were included in the analysis. Clinical outcomes were better in patients randomized to the nerinetide arm (mRS 0–2: 59.4% vs. 49.8%). There was possible treatment effect modification by ASPECTS score; patients with ASPECTS 8–10 showed a larger treatment effect compared to those with lower ASPECTS score. Younger age, lower NIHSS score, lower baseline serum glucose, absence of atrial fibrillation at baseline, higher ASPECTS score, middle cerebral artery (vs. internal carotid artery) occlusion, use of conscious or no sedation (vs. general anesthesia), and faster treatment were all predictors of favorable outcome.
Conclusion
Patients in the nerinetide arm who were not treated with concurrent alteplase showed improved clinical outcomes and the treatment effect was larger among patients with favorable ASPECTS profiles.
4.Bifidobacterium pseudocatenulatum ATCC 27919 exopolysaccharides induced autophagy and apoptosis against endoplasmic reticulum stress in Caco-2 cells
Husna Zulkipli ; Hifa Nazirah Mohammed Yaziz ; Mohd Yusri Idorus ; Siti Hamimah Sheikh Abdul Kadir ; Maslinda Musa ; Khalilah Abdul Khalil
Malaysian Journal of Microbiology 2023;19(no.5):545-559
Aims:
This study aimed to investigate the effect of exopolysaccharide (EPS) from Bifidobacterium pseudocatenulatum ATCC 27919 in Caco-2 cells on apoptotic and autophagic pathways.
Methodology and results:
Cell viability was examined by MTS assay and it showed a significant decrease in Caco-2 cells after exposure to EPS. Microscopy imaging and morphological analyses demonstrated that EPS-exposed Caco-2 cells exhibited the main morphological characteristics of apoptosis. EPS-exposed cells showed early apoptosis and cell cycle arrest at the G2/M phase in the cell cycle and dead cell assays. qPCR suggested that mRNA expression of substantial apoptotic markers such as cleaved Caspase-3, BAX and PARP-1 were significantly increased in EPS-exposed cells. The autophagy event was demonstrated in EPS-exposed cells by the contrary mRNA expression of Beclin-1 and Bcl-2 and the detection of autophagic LC3-II protein at 24 h exposure. GRP78 mRNA expression was also increased in EPS-exposed cells, indicating the occurrence of endoplasmic reticulum (ER) stress.
Conclusion, significance and impact of study
Autophagy activity in EPS-exposed Caco-2 cells preceded apoptosis, suggesting it was a cytoprotective response against ER stress. Research findings set the foundation for therapeutic CRC treatments and provide insight into its regulatory processes.
5.THE LEVEL OF KNOWLEDGE, ATTITUDE AND PRACTICE TOWARDS COVID-19 IMMUNISATION AMONG MEDICAL STUDENTS IN PUBLIC MEDICAL SCHOOLS IN MALAYSIA
Nurul Hayati Mohamad Zainal ; Safiyya Mohammed Ayyub ; Fang Yi Chang ; Arif Najmi Shahrir Zaman ; Nurul Huda Mohd Nor ; Norsuhana Omar ; Ku Mastura Ku Mohd Noor ; Hanan Hamimi Wahid
Journal of University of Malaya Medical Centre 2023;26(2):70-80
COVID-19 is a highly contagious disease that caused a worldwide pandemic in 2020. Medical students are public advocates for COVID-19 vaccination to achieve herd immunity. Our objective is to ascertain the level of knowledge, attitude, and practice toward COVID-19 immunisation among medical students in Malaysia. The online study included four public universities in Peninsular Malaysia: Universiti Putra Malaysia, International Islamic University Malaysia, Universiti Sains Malaysia and Universiti Sains Islam Malaysia. Data collected include sociodemographic characteristics, history of COVID-19 infection, knowledge, attitude and practice towards COVID-19 immunisation. Analytical statistics were analysed with IBM Statistical Package Statistical Package for the Social Science (SPSS) v27.0 using Pearson chi-square or Fisher’s exact test (significant if p < 0.05). From the total of 427 respondents, 60.2% had good knowledge whereby clinical students 67.0% had a higher proportion of good knowledge as compared to preclinical students 53.5% (p = 0.004). Respondents in the age group of 21 to 24 years old (p < 0.001) and 25 to 29 years old (p = 0.016), and Indian ethnicity (p = 0.006) were more likely to have good knowledge. Respondents registered in Malaysia’s National COVID-19 vaccination program were considered as having a positive attitude (n = 264, 61.8%). A vaccination rate of 100% was observed. In conclusion, 60.2% of medical students had good knowledge, 61.8% had a positive attitude and 100% were vaccinated in these four public medical schools in Malaysia. Sociodemographic factors (age group and Indian ethnicity) have an association with only good knowledge but none with the level of attitude and practice towards COVID-19 immunisation.
COVID-19
6.Expression of virulence genes in Group B Streptococcus isolated from symptomatic pregnant women with term and preterm delivery
Hanan Hamimi Wahid ; Puteri Fara Diba Mustapha Rounal ; Arvind Raaj Selvakumaran ; Fatin Najihah Anahar ; Mohammed Imad Al-Deen Mustafa Mahmud ; Norsyuhada Alias ; Norhidayah Kamarudin ; Roesnita Baharudin ; Roziah Husin ; Ahmad Muzamir Ahmad Mustafa ; Hamizah Ismail
Malaysian Journal of Microbiology 2022;18(4):370-379
Aims:
Maternal vaginal Group B Streptococcus (GBS) colonization is considered a risk factor for preterm delivery and, consequently, neonatal infections. Previous studies have portrayed the important roles of these virulence factors, including hemolytic pigment, hyaluronidase (HylB), serine-rich protein (Srr) and bacterial surface adhesion of GBS (BsaB) in mediating GBS colonization and intrauterine ascending infection, causing preterm delivery. This study aimed to investigate the association between mRNA expression of virulence genes in GBS isolates obtained from symptomatic pregnant women and preterm delivery.
Methodology and results:
GBS isolates were obtained from high vaginal swabs of 40 symptomatic pregnant women of gestational age of less than 37 weeks. RNA was extracted from these GBS isolates and RT-qPCR was performed to determine the relative mRNA expression of GBS virulence genes, including CylE (encode enzyme required for the biosynthesis of the hemolytic pigment), HylB, Srr-1 and BsaB. Socio-demographic details and obstetric history were not found to be associated with the delivery outcomes of these women. The GBS isolates from symptomatic pregnant women who delivered prematurely showed a higher expression of CylE gene and a trend towards an elevated expression of HylB gene compared to women with term delivery. Meanwhile the expression of both Srr-1 and BsaB genes was similar between symptomatic pregnant women who had term or preterm delivery.
Conclusion, significance and impact of study
The results suggest that following vaginal colonization, both CylE and HylB genes are likely to contribute to intrauterine ascending infection and inflammation, leading to preterm delivery in humans. These virulence factors may be targeted for the pre-clinical stages of vaccine development or therapeutic intervention.
Streptococcus agalactiae--isolation &
;
purification
;
Pregnant Women
7.Understanding the Negative Public Perception on Vaccination in West Coast and East Coast Peninsular Malaysia
Sakina Ruhi ; Puteri Nabilah ; Sohayla M. Attalla ; Mohamed Treki ; Jiyauddin Khan ; Aminu Ishaka ; Shariq Baber ; Mohammed Kaleemullah ; Salman Hasan
Malaysian Journal of Medicine and Health Sciences 2021;17(No.1):77-82
Introduction: Vaccination is a biological process that improves immunity level of an individual towards certain diseases. Vaccination is generally given to all newborn and kids. Most countries oblige their citizens to be vaccinated as
early as new-born age. The aim of this research is to study the perception on vaccination intake and the associated
factors that lead to its refusal among parents in east coast and west coast peninsular Malaysia. Methods: Primary
data were collected using self-administered questionnaire and were distributed to assess the study objectives. Total
240 questionnaires were distributed equally in west coast and east coast study area. Questionnaire consists of demographic data, perception aspects and factors that may lead to the negative perceptions. Results: There is significant
association between perception and religion, education level and side effect factor in east coast with majority of the
respondents are Muslims (40.83%) while there is no significant association between education level and side effect
factor (p>0.1) in west coast with majority of respondents are Muslims (51.67%) too. This study found that perception
regarding vaccination is influenced by the religion restrictions in east coast of peninsular Malaysia and not in west
coast region. The other factors associated with vaccination refusal varies according to education level, and regional
basis. Conclusion: Most of the respondents who have negative perception regarding vaccination are from East Coast
region as they are more prone into Islamic teachings. All the possible factors of vaccination refusal are accepted by
the respondents but varies in its prevalence as the leading factor determined that caused the vaccination refusal are
religion restriction and the least percentage for the factor is time restriction.
8.The Study of Knowledge, Attitude and Practice of Prostate Cancer Prevention and Its Relationship With Socio-demographic Characteristics Among Men at Ppr Lembah Subang 1, Selangor, Malaysia
Mohammed Faez Baobaid ; Mohammed A. Abdalqader ; Hasanain Faisal Ghazi ; Hesham Shebl ; Haitham Assem Abdalrazak
Malaysian Journal of Medicine and Health Sciences 2020;16(Supp 7, Aug):46-51
Introduction: Prostate cancer is one of the most common causes of cancer deaths among men worldwide. In Malaysia however, it is the fifth leading cause of cancer among men. The increases of prostate cancer among men in Malaysia due to its close association with lack of awareness, poor knowledge and attitude. Therefore, this study is to obtain information on the prostate in terms of the level of awareness, perception, and the practice of prevention of prostate cancer among Malaysians, particularly residents of PPR Lembah Subang 1. Methods: A cross-sectional survey was collected among 200 respondents aged 18 years and above in PPR Lembah Subang 1 consisting of 37 questions comprised of socio-demographic data, source of information, risk factors, knowledge on prostate cancers, attitude on prostate cancer and practice of prevention. Likert scale scoring system used in this research. Results: Men in PPR Lembah Subang 1, show a significant association between knowledge on prostate cancer with age group, level of education, and family history showing (p value: <0.001), (p value: 0.01), (p value: 0.03), respectively. There is an association between attitude towards prostate cancer and age group and income level both with (p value: <0.001). The findings showed a significant association between the practice of prevention towards prostate cancer with level income and education showing (p value: <0.001) and (p value: 0.01) respectively. Conclusion: In PPR Lembah Subang, knowledge, attitude , and practice of prevention of Prostate Cancer found to be associated with socio-demographic risk factors.
9.Brain Tumours and Their Metabolic Profiles by Magnetic Resonance Spectroscopy
Manah Chandra Changmai ; Mohammed Faruque Reza ; Zamzuri idris ; Regunath Kandasamy ; Kastury Gohain
Malaysian Journal of Medicine and Health Sciences 2020;16(No.3, September):162-168
Introduction: Intracranial brain tumour like meningiomas and glioblastomas are most prevalent tumour. The metastasis to the brain is one of the major issues in the tumours of the central nervous system. The diagnosis of metastatic and primary brain tumour is incomprehensible with standard magnetic resonance imaging (MRI). The magnetic resonance spectroscopy (MRS) is basically performed in standard clinical setting for diagnosing and tracking the brain tumour. Method: It is a retrospective study containing 53 patients with MRS. The patients with metastatic tumour (n=10), glioblastomas (n=8) and meningiomas (n=20) are included in the study. Single voxel technique is applied in the tumour core to determine the metabolites. The tumour N-acetyl aspartate (NAA), Choline (Cho), Creatine (Cr), Lactate, Alanine and lipids were analysed. The ratios of NAA/Cr, Cho/NAA and Cho/Cr were recorded and compared between the three tumours. The metabolites were detected between short echo time (TE) to long echo time (TE) during MRS. Results: There is a sharp fall of NAA peak in metastatic tumour. The resonance of creatine, lactate and alanine is higher in glioblastomas. A high lipid mean value of 3.13(0.17) is seen in metastatic tumour. The ROC curve shows a low NAA/Cr specificity of 46.7%, high sensitivity of 83.3% in Cho/NAA and Cho/Cr ratio. Conclusion: The metabolic profiles of metastatic brain tumour, glioblastomas and meningioma illustrate a divergence in their description that will assist in planning therapeutic and surgical intervention of these tumours.
10.A Community Based Study on Tropical Phagedenic Ulcers in Shah Alam, Malaysia: Knowledge, Attitude and Practice
Asdren Zajmi ; Nur Atikah Adam ; Mohammed Abdelfatah Alhoot
Malaysian Journal of Medicine and Health Sciences 2020;16(Supp 1,January):112-117
Introduction: Tropical phagedenic ulcer is a skin disease caused by a cocktail of bacteria. This painful ulcer forms over the lower limbs. It is also associated with necrotic slough and foul-smelling discharge that eventually lead to amputation and permanent disabilities. Tropical phagedenic ulcer in Malaysia has not been given much attention. In light of this situation, this research was conducted to assess the knowledge, attitude and practice regarding tropical phagedenic ulcer among the public in Shah Alam, Selangor. Methods: The total respondents were 384, consisting of 164 males and 220 females who were randomly selected. Data were obtained qualitatively through structured questionnaires and analysed using the chi-square test to study the association between the dependent variables and demographic factors. Results: The collected data showed that the respondents (67.2%) had poor knowledge of tropical phagedenic ulcer; merely 65.4% considered it to be a health problem, whereas 29.7% believed it is contagious. Also, the data revealed an association between age (χ2=13.587, p =0.004), marital status (χ2=15.435, p=0.001), time spent in community (χ2=6.438, p=0.04) and knowledge of the local name of tropical phagedenic ulcer. About 74.7% of the respondents did not know the cause of tropical phagedenic ulcer. Only 22.1% of the respondents had encountered tropical phagedenic ulcer patients and an association was found between the variable with gender (χ2=4.672, p =0.031), age (χ2=24.134, p =0.000) and marital status (χ2=17.143, p =0.001). Conclusion: This study reveals misconceptions about the aetiology and transmission of tropical phagedenic ulcer which greatly influence the attitude of community members towards tropical phagedenic ulcer patients.


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