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Fulltext The association between perception of health during pregnancy and the risk of cardiovascular disease: a prospective study

Zulkifly HH, Clavarino A, Kassab YW, Dingle K

Springerplus, 2016;5:6.
PMID: 26759745 DOI: 10.1186/s40064-015-1639-6

There is some evidence that self-rated perceptions of health are predictive of objective health outcomes, including cardiovascular disease, and mortality. The objective of this study was to examine the prospective association between perceptions of health during pregnancy and cardiovascular risk factors of mothers 21 years after the pregnancy. Data used were from the Mater University Study of Pregnancy (MUSP), a community-based prospective birth cohort study begun in Brisbane, Australia, in 1981. Logistic regression analyses were conducted. Data were available for 3692 women. Women who perceived themselves as not having a straight forward pregnancy had twice the odds (adjusted OR 2.0, 95 % CI 1.1-3.8) of being diagnosed with heart disease 21 years after the pregnancy when compared with women with a straight forward pregnancy (event rate of 5.2 versus 2.6 %). Women who experienced complications (other than serious pregnancy complications) during their pregnancy were also at 30 % increased odds (adjusted OR 1.3, 95 % CI 1.0-1.6) of having hypertension 21 years later (event rate of 25.7 versus 20 %). As a whole, our study suggests that pregnant women who perceived that they had complications and did not have a straight forward pregnancy were likely to experience poorer cardiovascular outcomes 21 years after that pregnancy.
Fulltext Empirical use of antibiotic therapy in the prevention of early onset sepsis in neonates: a pilot study

Manan MM, Ibrahim NA, Aziz NA, Zulkifly HH, Al-Worafi YM, Long CM

Arch Med Sci, 2016 Jun 1;12(3):603-13.
PMID: 27279855 DOI: 10.5114/aoms.2015.51208

To identify and assess the characteristics, risk and outcome of neonates treated with empiric antibiotics for suspected early onset sepsis (EOS).
Fulltext Relation of the time in therapeutic range (TTR) of warfarin to bleeding incidences in patients with atrial fibrillation [Abstract]

Jasmi MA, Mazlan MN, Shaharuddin S, Zulkifly HH, Long CM, Hashim R, et al.

Value Health, 2014 Nov;17(7):A478.
PMID: 27201388 DOI: 10.1016/j.jval.2014.08.1375

Conference abstract;
Objectives: Warfarin use in atrial fibrillation has been established for preventing occurrence of stroke in patients with atrial fibrillation. However, safety and clinical monitoring of warfarin use is crucial due to its risk of bleeding complications. This study aims to compare and establish relation of time in therapeutic range (TTR) of warfarin in patients with atrial fibrillation in the first 6 months and 6 month thereafter of anticoagulation therapy.
Methods: This is a retrospective study carried out at a tertiary-care hospital with anticoagulation clinic in the state of Selangor, Malaysia. Data collected included patients’ demographics, co-morbidities, and international normalized ratio (INR). TTR were determined using Rosendaal method based on records found in database (INR Desk 4.0 system) and patients’ hemorrhage events were also recorded. Samples of the study were patient who started warfarin from January 2009 until March 2013.
Results: A total of 167 patients with atrial fibrillation were enrolled and only 6% (n=10) achieved TTR of more than 75% for the first 6 months of warfarin use as compared to 16.8% (n=28) of TTR more than 75% 6 months thereafter. As for bleeding incidences, 29% (n=45) of patients in the group of TTR less than 75% in the first 6 months had bleeding complications as compared to 18.7% (n=26) in patients of TTR less than 75% 6 months after.
Conclusions: A more regular follow up is necessary during the first 6 months of new warfarin users as they tend to be out of the TTR and have a higher bleeding risk.
Study site: anticoagulation clinic, tertiary hospital, Selangor, Malaysia
Fulltext Report: trends in adherence to secondary prevention medications in post-acute coronary syndrome patients

Kassab YW, Hassan Y, Aziz NA, Zulkifly HH, Iqbal MS

Pak J Pharm Sci, 2015 Mar;28(2):641-6.
PMID: 25730796

To evaluate patients' adherence to evidence-based therapies at an average of 2 years after discharge for Acute Coronary Syndrome (ACS) and to identify factors associated with non-adherence. This study was conducted at Hospital Pulau Pinang, Malaysia. A random sample of ACS patients (n=190) who had discharged on a regimen of secondary preventive medications were included and followed up over a three follow-up appointments at 8, 16, and 23 months post discharge. At each appointment, patients were interviewed and given Morisky questioner to complete in order to compare their level of adherence to the prescribed regimens across the three consecutive time periods. Majority of patients reported either medium or low adherence across the three time periods with only small portion reported high adherence. Furthermore, there was a significant downward trend in the level of adherence to cardio protective medications during the study period (p<0.001). This study also identified 6 factors-age, gender, employment status, ACS subtype, number of co morbidities and number of prescription medications per day that may influence Patients' adherence to their medications. Our findings suggest that long-term adherence to secondary prevention therapies among patients with ACS in Malaysia is sub optimal and influenced by many demographic, social as well as clinical factors.
Preliminary study of safety and efficacy of warfarin versus dabigatran in atrial fibrillation patients in a tertiary hospital in Malaysia [Abstract]

Mohd Hajiri M, Shaharuddin S, Long CM, Hashim R, Zulkifly HH, Kasim SS, et al.

Value Health, 2015 Nov;18(7):A378.
PMID: 26532133 DOI: 10.1016/j.jval.2015.09.795

Conference abstract:
Objectives: Warfarin has been used for more than 50 years as stroke prophylaxis in patients with atrial fibrillation. New oral anticoagulant, Dabigatran, was developed and shown to be safer and more efficacious compared to Warfarin due to its lower tendency of bleeding and in reducing stroke incidences. This study aims to compare the pattern of anticoagulants used and to assess their safety and efficacy by evaluating bleeding and stroke occurrences in both groups.
Methods: This is a retrospective study carried out at a hospital with hematology clinic in the state of Selangor, Malaysia. The samples of the study were patients with atrial fibrillation, prescribed with warfarin or dabigatran. Data collected includes patients’ demographics, co-morbidities, and stroke and haemorrhage events.
Results: A total of 71 patients were recruited in this study with 21, 21 and 29 patients were on Warfarin, Dabigatran 110 mg and Dabigatran 150 mg respectively. Out of 50 Dabigatran users, 36 of them are warfarin-experienced. 1 out of 21 patients on warfarin experienced stroke while none in both 110 and 150mg dabigatran group. A total of 11 (52.4%) of warfarin patients experienced bleeding with 2 of them having major bleeding whereas, only 4 (8%) out of 50 dabigatran patients experienced minor bleeding, 1 in patient who were on Dabigatran 150mg and 3 patients who were on Dabigatran 110mg.
Conclusions: The pattern of anticoagulant used for stroke prophylaxis in atrial fibrillation is slowly changing from Warfarin to Dabigatran. Evaluation of safety and efficacy profile of Warfarin shows that Warfarin requires more extensive management and monitoring in order to achieve therapeutic goals with fewer side effects. Comparison between both anticoagulants show that Dabigatran is safer and more effective compared to warfarin
Study site: Haematology clinic, hospital, Selangor, Malaysia
Relationship of Time in Therapeutic Range (Ttr) with Bleeding and Stroke Incidences of Warfarinised Patients with Pulmonary Embolism in a Tertiary Hospital in Malaysia

Sudirman N, Shaharuddin S, Long CM, Hashim R, Zulkifly HH, Kasim SS, et al.

Value Health, 2015 Nov;18(7):A378.
PMID: 26532135 DOI: 10.1016/j.jval.2015.09.794
Fulltext Anticoagulation Control in Different Ethnic Groups Receiving Vitamin K Antagonist for Stroke Prevention in Atrial Fibrillation

Zawawi NA, Abdul Halim Zaki I, Ming LC, Goh HP, Zulkifly HH

Front Cardiovasc Med, 2021;8:736143.
PMID: 34869639 DOI: 10.3389/fcvm.2021.736143

Vitamin K antagonist such as warfarin reduces the risk of stroke in atrial fibrillation (AF) patients. Since warfarin has a narrow therapeutic index, its administration needs to be regularly monitored to avoid any adverse clinical outcomes such as stroke and bleeding. The quality of anticoagulation control with warfarin therapy can be measured by using time in therapeutic range (TTR). This review focuses on the prevalence of AF, quality of anticoagulation control (TTR) and adverse clinical outcome in AF patients within different ethnic groups receiving warfarin therapy for stroke prevention. A literature search was conducted in Embase and PubMed using keywords of "prevalence," "atrial fibrillation," "stroke prevention," "oral anticoagulants," "warfarin," "ethnicities," "race" "time in therapeutic range," "adverse clinical outcome," "stroke, bleeding." Articles published by 1st February 2020 were included. Forty-one studies were included in the final review consisting of AF prevalence (n = 14 studies), time in therapeutic range (n = 18 studies), adverse clinical outcome (n = 9 studies) within different ethnic groups. Findings indicate that higher prevalence of AF but better anticoagulation control among the Whites as compared to other ethnicities. Of note, non-whites had higher risk of strokes and bleeding outcomes while on warfarin therapy. Addressing disparities in prevention and healthcare resource allocation could potentially improve AF-related outcomes in minorities.
A systematic review of thromboembolic complications and outcomes in hospitalised COVID-19 patients

Othman HY, Zaki IAH, Isa MR, Ming LC, Zulkifly HH

BMC Infect Dis, 2024 May 10;24(1):484.
PMID: 38730292 DOI: 10.1186/s12879-024-09374-1

Thromboembolic (TE) complications [myocardial infarction (MI), stroke, deep vein thrombosis (DVT), and pulmonary embolism (PE)] are common causes of mortality in hospitalised COVID-19 patients. Therefore, this review was undertaken to explore the incidence of TE complications and mortality associated with TE complications in hospitalised COVID-19 patients from different studies. A literature search was performed using ScienceDirect and PubMed databases using the MeSH term search strategy of "COVID-19", "thromboembolic complication", "venous thromboembolism", "arterial thromboembolism", "deep vein thrombosis", "pulmonary embolism", "myocardial infarction", "stroke", and "mortality". There were 33 studies included in this review. Studies have revealed that COVID-19 patients tend to develop venous thromboembolism (PE:1.0-40.0% and DVT:0.4-84%) compared to arterial thromboembolism (stroke:0.5-15.2% and MI:0.8-8.7%). Lastly, the all-cause mortality of COVID-19 patients ranged from 4.8 to 63%, whereas the incidence of mortality associated with TE complications was between 5% and 48%. A wide range of incidences of TE complications and mortality associated with TE complications can be seen among hospitalized COVID-19 patients. Therefore, every patient should be assessed for the risk of thromboembolic complications and provided with an appropriate thromboprophylaxis management plan tailored to their individual needs.
Fulltext COVID-19 vaccine-induced immune thrombotic thrombocytopenia: a review

Suhaimi SNAA, Zaki IAH, Noordin ZM, Hussin NSM, Ming LC, Zulkifly HH

Clin Exp Vaccine Res, 2023 Oct;12(4):265-290.
PMID: 38025914 DOI: 10.7774/cevr.2023.12.4.265

Rare but serious thrombotic incidents in relation to thrombocytopenia, termed vaccine-induced immune thrombotic thrombocytopenia (VITT), have been observed since the vaccine rollout, particularly among replication-defective adenoviral vector-based severe acute respiratory syndrome coronavirus 2 vaccine recipients. Herein, we comprehensively reviewed and summarized reported studies of VITT following the coronavirus disease 2019 (COVID-19) vaccination to determine its prevalence, clinical characteristics, as well as its management. A literature search up to October 1, 2021 using PubMed and SCOPUS identified a combined total of 720 articles. Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline, after screening the titles and abstracts based on the eligibility criteria, the remaining 47 full-text articles were assessed for eligibility and 29 studies were included. Findings revealed that VITT cases are strongly related to viral vector-based vaccines, which are the AstraZeneca COVID-19 vaccine (95%) and the Janssen COVID-19 vaccine (4%), with much rarer reports involving messenger RNA-based vaccines such as the Moderna COVID-19 vaccine (0.2%) and the Pfizer COVID-19 vaccine (0.2%). The most severe manifestation of VITT is cerebral venous sinus thrombosis with 317 cases (70.4%) and the earliest primary symptom in the majority of cases is headache. Intravenous immunoglobulin and non-heparin anticoagulant are the main therapeutic options for managing immune responses and thrombosis, respectively. As there is emerging knowledge on and refinement of the published guidelines regarding VITT, this review may assist the medical communities in early VITT recognition, understanding the clinical presentations, diagnostic criteria as well as its management, offering a window of opportunity to VITT patients. Further larger sample size trials could further elucidate the link and safety profile.
Assessing the Predictive Value of the SAMe-TT2R2 Score for Poor Anticoagulation Control in a Diverse Ethnic Population

Mohamed S, Nik Abdul Rahman NN, Tan JY, Selvam T, Zulkifly HH, Cardiology Subspecialty Working Committee

Hosp Pharm, 2024 Nov 29.
PMID: 39619886 DOI: 10.1177/00185787241300293

Introduction: In Asian countries, warfarin is still widely used for stroke prevention in non-valvular atrial fibrillation compared to non-vitamin K antagonist oral anticoagulants (NOACs) due to its affordability. A tool such as the SAMe-TT2R2 is needed to determine the probability of achieving and maintaining good anticoagulation control with warfarin therapy. However, it requires validation in the Malaysian cohort. Therefore, the objective of our study is to validate the SAMe-TT2R2 score in predicting poor anticoagulation control in Malaysia. A time in therapeutic range (TTR) 5 best predicts poor anticoagulation control with a sensitivity of 0.49 and a specificity value of 0.68. Conclusion: The SAMe-TT2R2 score, especially when exceeding 5, was associated with a higher likelihood of poor anticoagulation control, emphasizing its relevance in clinical assessment. However, its limited predictive capability, reflected by a C-statistic of 0.548, suggests the need for cautious interpretation and consideration of additional factors in anticoagulation management decisions. Continuous monitoring and personalized strategies are crucial for optimizing outcomes in this population.
Fulltext Amino acid dosing in parenteral nutrition for very low birth weight preterm neonates: an outcome assessment

Kamarudin NA, Manan MM, Zulkifly HH, Neoh CF, Ali SM, Ming LC

Asia Pac J Clin Nutr, 2016;25(1):53-61.
PMID: 26965762 DOI: 10.6133/apjcn.2016.25.2.02

This study aimed to investigate the effects of parenteral nutrition (PN) administration of amino acids (AA) on physical changes among very low birth weight infants in a local hospital setting in Malaysia. A retrospective study was carried out at a hospital in Malaysia. Records of neonates prescribed PN in the neonatal unit in 2012 were screened for eligibility. A total of 199 premature neonates received PN support in the year 2012 and, of these, 100 fulfilled the inclusion criteria. The median value of AA intake on the first day of PN was 2.00 (<28 weeks group); 1.00 (28-31 weeks group) and 0.75 (>31 weeks group). Neonates in the <28 weeks group were more likely to receive AA at an earlier time and higher initial dose compared with the other age groups. The study also found that there was no statistically significant difference in the dose of AA on the first day of PN administration and that the significant variations in nutritional parameters among the subjects did not lead to differences in physical outcomes. This study identified that when PN is provided in the local hospital setting, it is likely that the current nutritional practices are inadequate to achieve the standard growth recommendations. Our findings call for a need to optimize AA and calorie intake since growth restriction is a morbidity which will affect the infants' growth and development. Current prescriptions for PN in this hospital need to be reviewed in order to improve patient outcomes.
Fulltext A Review of the Prevalence of Thromboembolic Complications among Pregnant Women Infected with COVID-19

Mohd Ariff NS, Abdul Halim Zaki I, Mohd Noordin Z, Md Hussin NS, Goh KW, Ming LC, et al.

J Clin Med, 2022 Oct 08;11(19).
PMID: 36233801 DOI: 10.3390/jcm11195934

Background: Thrombotic conditions triggered by SARS-CoV-2 virus can result in high mortality, especially in pregnant women as they are already in a hypercoagulability state. This thereby leads to excessive inflammation that will increase the risk of thromboembolic (TE) complications. Objective: The aim of this study is to review the prevalence of thromboembolic complications such as deep venous thrombosis, pulmonary embolism, and intervillous thrombosis, and their preventive strategies among pregnant women infected with COVID-19. Method: The articles were retrieved from online databases PubMed and ScienceDirect published from February 2020 to April 2022. Findings: A total of 5249 participants including 5128 pregnant women and 121 placentas from 19 studies were identified for having TE complications after being infected with COVID-19. The types of TE complications that developed within pregnant women were disseminated intravascular coagulation (DIC) (n = 44, 0.86%), unmentioned thromboembolic complications (TE) (n = 14, 0.27%), intervillous thrombosis (IVT) (n = 9, 0.18%), pulmonary embolism (PE) (n = 6, 0.12%), COVID-19 associated coagulopathy (CAC) (n = 5, 0.10%), and deep venous thrombosis (DVT) (n = 2, 0.04%). Whereas the prevalence of TE complications reported from studies focusing on placenta were IVT (n = 27, 22.3%), subchorionic thrombus (SCT) (n = 9, 7.44%), and placental thrombosis (n = 5, 4.13%). Thromboprophylaxis agent used among pregnant women include low molecular weight heparin (LMWH) at prophylactic dose (n = 9). Conclusions: The prevalence of thromboembolic complications among pregnant women infected by COVID-19 is low with DIC being the most common form and placental thrombosis being the least common form of TE complications that occurred within pregnant women infected with COVID-19. Anticoagulation, in particular LMWH (variable dose), is frequently used to prevent TE complications.
Fulltext Coriandrum sativum L.: A Review on Ethnopharmacology, Phytochemistry, and Cardiovascular Benefits

Mahleyuddin NN, Moshawih S, Ming LC, Zulkifly HH, Kifli N, Loy MJ, et al.

Molecules, 2021 Dec 30;27(1).
PMID: 35011441 DOI: 10.3390/molecules27010209

Coriandrum sativum (C. sativum), belonging to the Apiaceae (Umbelliferae) family, is widely recognized for its uses in culinary and traditional medicine. C. sativum contains various phytochemicals such as polyphenols, vitamins, and many phytosterols, which account for its properties including anticancer, anti-inflammatory, antidiabetic, and analgesic effects. The cardiovascular benefits of C. sativum have not been summarized before, hence this review aims to further evaluate and discuss its effectiveness in cardiovascular diseases, according to the recent literature. An electronic search for literature was carried out using the following databases: PubMed, Scopus, Google Scholar, preprint platforms, and the Cochrane Database of Systematic Reviews. Articles were gathered from the inception of the database until August 2021. Moreover, the traditional uses and phytochemistry of coriander were surveyed in the original resources and summarized. As a result, most of the studies that cover cardiovascular benefits and fulfilled the eligibility criteria were in vivo, while only a few were in vitro and clinical studies. In conclusion, C. sativum can be deemed a functional food due to its wide range of cardiovascular benefits such as antihypertensive, anti-atherogenic, antiarrhythmic, hypolipidemic as well as cardioprotective effects.
Fulltext The prevalence of thromboembolic events among COVID-19 patients admitted to a single centre intensive care unit (ICU): an epidemiological study from a Malaysian population

Mansor NF, Abdul Halim Zaki I, Kiok LC, Seng EK, Ravi T, Pathmanathan M, et al.

J Pharm Policy Pract, 2025;18(1):2449044.
PMID: 39917475 DOI: 10.1080/20523211.2024.2449044

INTRODUCTION: Thromboembolic (TE) complications in COVID-19 patients are rising globally, contributing significantly to mortality, particularly in severe cases. However, their prevalence, characteristics, and impact on mortality in Malaysia remain unclear.
OBJECTIVES: This study aimed to determine the prevalence of thromboembolic (TE) events and associated mortality among COVID-19 patients admitted within a single centre intensive care unit (ICU). The proportions of patients with TE events who died, and factors associated with TE events were explored.
METHODS: In this retrospective cohort study, patients with PCR confirmed SARS-CoV-2 virus and who received thromboprophylaxis within February 2020-2021 were included. TE event is a combination of venous [(deep vein thrombosis (DVT), pulmonary embolism (PE)] and arterial (myocardial infarction (MI), stroke) thromboembolism.
RESULTS: Mean (SD) age 56.6 (13.7), 63.5% were male, 61.6% Malays, median (IQR) 7 (3-14) days of ICU stay, 64.2%, 53.2% and 20.9% had underlying hypertension, diabetes and obesity respectively. In total, 240 (44.9%) developed TE event. Significantly higher proportions of COVID-19 patients who developed complications of DVT (2.5% vs. 0.2%; p = 0.013), PE (47.5% vs 34.0%; p = 0.006), stroke (12.3% vs. 1.5; p<0.001) and MI (16.4% vs. 4.6%; p<0.001) died. Predictors of TE events were age [HR 1.01 (95% CI 1.00-1.02)], obesity [HR 1.98 (95% CI 1.51-2.6)], D-dimer [HR 1.01 (95% CI 1.00-1.01)], and duration of ICU stay [HR 0.98 (95% CI 0.97-0.99)].
CONCLUSION: In severely ill COVID-19 patients, TE complications were common, and patients with DVT, PE, stroke, or MI faced increased mortality, even with thromboprophylaxis. Age, obesity, elevated D-Dimer levels, and longer ICU stays were significant predictors of TE events. Considering these findings, a more aggressive approach, combining thromboprophylaxis with enhanced anti-inflammatory treatments, may be necessary for high-risk COVID-19 ICU patients to reduce TE events and mortality.

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