Displaying publications 1 - 20 of 38 in total

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  1. Rehman AU, Hassali MAA, Muhammad SA, Harun SN, Shah S, Abbas S
    Eur J Health Econ, 2020 Mar;21(2):181-194.
    PMID: 31564007 DOI: 10.1007/s10198-019-01119-1
    OBJECTIVES: To find the economic burden of COPD and to identify the key cost drivers in the management of COPD patients across different European countries.

    BACKGROUND: COPD is a major cause of mortality and morbidity and is associated with considerable economic burden on the individual and society. It limits the daily activities and working ability of the patients.

    METHODOLOGY: We conducted a systematic search of PUBMED, SCIENCE DIRECT, Cochrane CENTRAL, SCOPUS, Google Scholar and SAGE Premier Databases to find scientific research articles evaluating the cost of COPD management from patient and societal perspective.

    RESULTS: Estimated per patient per year direct cost in Norway, Denmark, Germany, Italy, Sweden, Greece, Belgium, and Serbia was €10,701, €9580, €7847, €7448, €7045, €2896, €1963, and €2047, respectively. Annual per patient cost of work productivity loss was highest in Germany as €5735 and lowest in Greece as €998. It was estimated as €4824, €2033 and €1298 in Bulgaria, Denmark and Sweden, respectively. Several factors found associated with increasing cost of COPD management that include but not limited to late diagnosis, severity of disease, frequency of exacerbation, hospital readmissions, non-adherence to the therapy and exposure to COPD risk factors.

    CONCLUSION: Minimizing the COPD exacerbations and controlling the worsening of symptoms may potentially reduce the cost of COPD management at any stage.

  2. Yusoh NA, Leong SW, Chia SL, Harun SN, Rahman MBA, Vallis KA, et al.
    ACS Chem. Biol., 2020 02 21;15(2):378-387.
    PMID: 31898884 DOI: 10.1021/acschembio.9b00843
    There is a need to improve and extend the use of clinically approved poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi), including for BRCA wild-type triple-negative breast cancer (TNBC). The demonstration that ruthenium(II) polypyridyl complex (RPC) metallointercalators can rapidly stall DNA replication fork progression provides the rationale for their combination alongside DNA damage response (DDR) inhibitors to achieve synergism in cancer cells. The aim of the present study was to evaluate use of the multi-intercalator [Ru(dppz)2(PIP)]2+ (dppz = dipyrido[3,2-a:2',3'-c]phenazine, PIP = (2-(phenyl)imidazo[4,5-f][1,10]phenanthroline, Ru-PIP) alongside the PARPi olaparib and NU1025. Cell proliferation and clonogenic survival assays indicated a synergistic relationship between Ru-PIP and olaparib in MDA-MB-231 TNBC and MCF7 human breast cancer cells. Strikingly, low dose Ru-PIP renders both cell lines hypersensitive to olaparib, with a >300-fold increase in olaparib potency in TNBC, the largest nongenetic PARPi enhancement effect described to date. A negligible impact on the viability of normal human fibroblasts was observed for any combination tested. Increased levels of DNA double-strand break (DSB) damage and olaparib abrogation of Ru-PIP-activated pChk1 signaling are consistent with PARPi-facilitated collapse of Ru-PIP-associated stalled replication forks. This results in enhanced G2/M cell-cycle arrest, apoptosis, and decreased cell motility for the combination treatment compared to single-agent conditions. This work establishes that an RPC metallointercalator can be combined with PARPi for potent synergy in BRCA-proficient breast cancer cells, including TNBC.
  3. Yusoh NA, Tiley PR, James SD, Harun SN, Thomas JA, Saad N, et al.
    J Med Chem, 2023 May 25;66(10):6922-6937.
    PMID: 37185020 DOI: 10.1021/acs.jmedchem.3c00322
    Synergistic drug combinations can extend the use of poly(ADP-ribose) polymerase inhibitors (PARPi) such as Olaparib to BRCA-proficient tumors and overcome acquired or de novo drug resistance. To identify new synergistic combinations for PARPi, we screened a "micro-library" comprising a mix of commercially available drugs and DNA-binding ruthenium(II) polypyridyl complexes (RPCs) for Olaparib synergy in BRCA-proficient triple-negative breast cancer cells. This identified three hits: the natural product Curcumin and two ruthenium(II)-rhenium(I) polypyridyl metallomacrocycles. All combinations identified were effective in BRCA-proficient breast cancer cells, including an Olaparib-resistant cell line, and spheroid models. Mechanistic studies indicated that synergy was achieved via DNA-damage enhancement and resultant apoptosis. Combinations showed low cytotoxicity toward non-malignant breast epithelial cells and low acute and developmental toxicity in zebrafish embryos. This work identifies RPC metallomacrocycles as a novel class of agents for cancer combination therapy and provides a proof of concept for the inclusion of metallocompounds within drug synergy screens.
  4. Halboup AM, Alzoubi KH, Abu-Farha RK, Harun SN, Al-Mohamadi A, Battah MM, et al.
    J Multidiscip Healthc, 2023;16:3689-3701.
    PMID: 38058461 DOI: 10.2147/JMDH.S442296
    BACKGROUND: The spread of monkeypox (mpox) worldwide poses a severe threat to human life. This virus leads to a disease with symptoms similar to smallpox in humans. To combat this threat, improving public knowledge and perception toward mpox is vital for public health preventive measures.

    METHODS: A cross-sectional survey was carried out in Yemen from December 2022 to March 2023 to investigate public perception and knowledge of mpox. Individuals were approached through social media platforms using a convenient sampling approach. Linear regression was used to determine the association between participants' knowledge (dependent variable) and explanatory variables.

    RESULTS: A total of 853 individuals consented to take part in the study. A significant proportion of respondents had a low knowledge level (N=572, 67.06%). Most participants knew about the nature of the diseases (75%, n=641), transmission mode (78.1%, n=668), hand sanitizer preventive measures, and skin- related symptoms. However, only 20.8% (n= 178) knew that diarrhea is not a symptom, and 25.4% (n= 217) knew antibiotics are unnecessary for mpox management. A proportion of 57.7% (n=492) of the participants feared human mpox, and 47.7% (n= 407) thought it was a conspiracy. Most participants had a good perception of local and international health authorities controlling the disease. Age, education level, having a health-related certificate, and receiving a 2-dose vaccination for COVID-19 had statistically significant associations with mpox knowledge level (P < 0.05). Social media platforms were the most often used information source about mpox (78.3%, n= 668), followed by articles (41.1%, n=351).

    CONCLUSION: The study reveals a low public knowledge about mpox in Yemen, emphasizing the need for targeted educational campaigns, especially via social media, to strengthen public health measures and disease control. Addressing Knowledge gaps and correcting misconceptions is crucial for improving preparedness and response to the disease.

  5. Dala Ali AHH, Harun SN, Othman N, Ibrahim B, Abdulbagi OE, Abdullah I, et al.
    Antibiotics (Basel), 2023 Aug 10;12(8).
    PMID: 37627725 DOI: 10.3390/antibiotics12081305
    In the management of sepsis, providing adequate empiric antimicrobial therapy is one of the most important pillars of sepsis management. Therefore, it is important to evaluate the adequacy of empiric antimicrobial therapy (EAMT) in sepsis patients admitted to intensive care units (ICU) and to identify the determinants of inadequate EAMT. The aim of this study was to evaluate the adequacy of empiric antimicrobial therapy in patients admitted to the ICU with sepsis or septic shock, and the determinants of inadequate EAMT. The data of patients admitted to the ICU units due to sepsis or septic shock in two tertiary healthcare facilities in Al-Madinah Al-Munawwarah were retrospectively reviewed. The current study used logistic regression analysis and artificial neural network (ANN) analysis to identify determinants of inadequate empiric antimicrobial therapy, and evaluated the performance of these two approaches in predicting the inadequacy of EAMT. The findings of this study showed that fifty-three per cent of patients received inadequate EAMT. Determinants for inadequate EAMT were APACHE II score, multidrug-resistance organism (MDRO) infections, surgical history (lower limb amputation), and comorbidity (coronary artery disease). ANN performed as well as or better than logistic regression in predicating inadequate EAMT, as the receiver operating characteristic area under the curve (ROC-AUC) of the ANN model was higher when compared with the logistic regression model (LRM): 0.895 vs. 0.854. In addition, the ANN model performed better than LRM in predicting inadequate EAMT in terms of classification accuracy. In addition, ANN analysis revealed that the most important determinants of EAMT adequacy were the APACHE II score and MDRO. In conclusion, more than half of the patients received inadequate EAMT. Determinants of inadequate EAMT were APACHE II score, MDRO infections, comorbidity, and surgical history. This provides valuable inputs to improve the prescription of empiric antimicrobials in Saudi Arabia going forward. In addition, our study demonstrated the potential utility of applying artificial neural network analysis in the prediction of outcomes in healthcare research.
  6. Harun SN, Holford NHG, Grimwood K, Wainwright CE, Hennig S, Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) study group
    Thorax, 2019 08;74(8):740-748.
    PMID: 31203197 DOI: 10.1136/thoraxjnl-2018-211548
    BACKGROUND: While Aspergillus detection rates in adults, adolescents and older children with cystic fibrosis (CF) have increased, the risk of acquiring this fungal pathogen in young children is unknown.

    AIM: To determine the risk and explanatory factors of acquiring Aspergillus in children with CF by age 5 years.

    METHODS: Cross-sectional analysis of clinical, bronchoalveolar lavage and treatment data from the Australasian Cystic Fibrosis Bronchoalveolar Lavage study was used to identify predictive factors for detecting Aspergillus at age 5 years. A parametric repeated time-to-event model quantitatively described the risk and factors associated with acquiring Aspergillus and Pseudomonas aeruginosa from birth until age 5 years.

    RESULTS: Cross-sectional analysis found that the number of P. aeruginosa eradication courses increased the odds of detecting Aspergillus at age 5 years (OR 1.61, 95% CI 1.23 to 2.12). The median (IQR) age for the first P. aeruginosa positive culture was 2.38 (1.32-3.79) years and 3.69 (1.68-4.74) years for the first Aspergillus positive culture. The risk of P. aeruginosa and Aspergillus events changes with time after the first year of study entry. It also decreases for P. aeruginosa after completing P. aeruginosa eradication (HR 0.15, 95% CI 0.00 to 0.79), but increases for Aspergillus events (HR 2.75, 95% CI 1.45 to 5.41). The risk of acquiring both types of events increases after having had a previous event.

    CONCLUSION: In young children with CF, completing P. aeruginosa eradication therapy and previous Aspergillus events are associated with increased risk of acquiring Aspergillus.

  7. Harun SN, Wainwright CE, Grimwood K, Hennig S, Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) study group
    Thorax, 2019 02;74(2):125-131.
    PMID: 30275132 DOI: 10.1136/thoraxjnl-2018-211550
    BACKGROUND: The impact of Aspergillus on lung disease in young children with cystic fibrosis is uncertain.
    AIMS: To determine if positive respiratory cultures of Aspergillus species are associated with: (1) increased structural lung injury at age 5 years; (2) accelerated lung function decline between ages 5 years and 14 years and (3) to identify explanatory variables.
    METHODS: A cross-sectional analysis of association between Aspergillus positive bronchoalveolar lavage (BAL) cultures and chest high-resolution CT (HRCT) scan findings at age 5 years in subjects from the Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) study was performed. A non-linear mixed-effects disease progression model was developed using FEV1% predicted measurements at age 5 years from the ACFBAL study and at ages 6-14 years for these subjects from the Australian Cystic Fibrosis Data Registry.
    RESULTS: Positive Aspergillus BAL cultures at age 5 years were significantly associated with increased HRCT scores for air trapping (OR 5.53, 95% CI 2.35 to 10.82). However, positive Aspergillus cultures were not associated with either FEV1% predicted at age 5 years or FEV1% predicted by age following adjustment for body mass index z-score and hospitalisation secondary to pulmonary exacerbations. Lung function demonstrated a non-linear decline in this population.
    CONCLUSION: In children with cystic fibrosis, positive Aspergillus BAL cultures at age 5 years were associated contemporaneously with air trapping but not bronchiectasis. However, no association was observed between positive Aspergillus BAL cultures on FEV1% predicted at age 5 years or with lung function decline between ages 5 years and 14 years.
  8. Harun SN, Hanafiah MM, Aziz NIHA
    Environ Manage, 2021 Jan;67(1):146-161.
    PMID: 33001258 DOI: 10.1007/s00267-020-01365-7
    This study aims to assess the environmental impacts of conventional and organic rice cultivations and proposes a sustainable conceptual framework of rice farming based on the life cycle assessment (LCA) approach. A cradle-to-gate LCA was performed by using the ReCiPe 2016 method and SimaPro 8.5 software. The functional unit was one ton of rice grains harvested. Primary data were obtained from the farmer, while secondary data were collected from Ecoinvent 3.0, the Agri Footprint 3.0 database and the literature. The total characterization factors for global warming potential (GWP), water consumption potential (WCP) and fossil fuel depletion potential (FFP) were 457.89 kg CO2-eq, 98.18 m3 and 84.56 kg oil-eq, respectively, at the midpoint level for conventional rice, while the impacts for organic rice were 140.55 kg CO2-eq, 29.45 m3 and 22.25 kg oil-eq, respectively. At the endpoint level, the total characterization factors for human health damage (HH), ecosystem damage (ED) and resource availability (RA) for conventional rice were 9.63 × 10-4 DALY, 5.54 × 10-6 species.year and 30.98 Dollar, respectively, while for organic rice, the impacts were 2.60 × 10-4 DALY, 2.28 × 10-6 species.year and 8.44 Dollar, respectively. Rice cultivation impacted the environment, particularly in relation to three impact categories: GWP, WCP and FFP. The cultivation phase of rice production was the main contributor to environmental impacts due to the production and application of fertilizer and pesticides. It can be concluded that the application of LCA in agricultural sector is able to provide information and responses for policy makers in understanding the potential environmental impacts at various spatial levels.
  9. Harun SN, Nordin SA, Gani SSA, Shamsuddin AF, Basri M, Basri HB
    Int J Nanomedicine, 2018;13:2571-2584.
    PMID: 29731632 DOI: 10.2147/IJN.S151788
    Background and aim: Drugs that are effective against diseases in the central nervous system and reach the brain via blood must pass through the blood-brain barrier (BBB), a unique interface that protects against potential harmful molecules. This presents a major challenge in neuro-drug delivery. This study attempts to fabricate the cefuroxime-loaded nanoemulsion (CLN) to increase drug penetration into the brain when parenterally administered.

    Methods: The nanoemulsions were formulated using a high-pressure homogenization technique and were characterized for their physicochemical properties.

    Results: The characterizations revealed a particle size of 100.32±0.75 nm, polydispersity index of 0.18±0.01, zeta potential of -46.9±1.39 mV, viscosity of 1.24±0.34 cps, and osmolality of 285.33±0.58 mOsm/kg, indicating that the nanoemulsion has compatibility for parenteral application. CLN was physicochemically stable within 6 months of storage at 4°C, and the transmission electron microscopy revealed that the CLN droplets were almost spherical in shape. The in vitro release of CLN profile followed a sustained release pattern. The pharmacokinetic profile of CLN showed a significantly higher Cmax, area under the curve (AUC)0-
    t
    , prolonged half-life, and lower total plasma clearance, indicating that the systemic concentration of cefuroxime was higher in CLN-treated rats as compared to cefuroxime-free treated rats. A similar profile was obtained for the biodistribution of cefuroxime in the brain, in which CLN showed a significantly higher Cmax, AUC0-
    t
    , prolonged half-life, and lower clearance as compared to free cefuroxime solution.

    Conclusion: Overall, CLN showed excellent physicochemical properties, fulfilled the requirements for parenteral administration, and presented improved in vivo pharmacokinetic profile, which reflected its practical approach to enhance cefuroxime delivery to the brain.

  10. 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.

  11. Daud NAA, Mohiuddin SG, Ong YP, Yusof F, Yusoff F, Harun SN, et al.
    J Pharm Bioallied Sci, 2021 05 26;13(2):230-237.
    PMID: 34349484 DOI: 10.4103/jpbs.JPBS_542_20
    Background: Metformin has been added in the Malaysian clinical practice guideline (CPG) as one of the first-line options in the management of gestational diabetes mellitus (GDM); however, the uptake on this practice among healthcare professionals is unknown.

    Objective: The objective of the study is to determine the awareness, attitude, and practice and their predictors on the use of metformin for GDM among healthcare professionals in Malaysia.

    Materials and Methods: This was a multicenter, cross-sectional study in three tertiary hospitals in Malaysia. Medical doctors and pharmacists working in several departments were invited to participate in a survey using self-administered questionnaires.

    Results: From 350 questionnaires distributed, 225 were completed by medical doctors (43.1%), pharmacists (40.4%), and specialists (7.5%). Less than 30% of them were aware on the option of using metformin as one of the first-line agents in GDM. Education level, department, and profession were found to be associated with the awareness level (P = 0.016, P = 0.004, and P = 0.001, respectively). 70.2% of the respondents showed a positive attitude toward metformin use in GDM. Only 64 (28.4%) of the respondents have prescribed/dispensed metformin for GDM before, although more than half will consider doing so in the future. Having postgraduate qualifications increased the likelihood of having a good awareness (odds ratio [OR]: 2.44, 95% confidence interval [CI] 1.23-4.85) and to consider prescribing/dispensing metformin for GDM patients (OR: 2.27, 95% CI 1.08-4.78).

    Conclusion: Despite a positive attitude toward metformin use in GDM among healthcare professionals in Malaysia, their awareness level on this practice was low as they currently prefer the use of insulin over metformin.

  12. Siddiqui S, Zainal H, Harun SN, Ghadzi SMS
    Clin Nutr ESPEN, 2020 10;39:165-172.
    PMID: 32859312 DOI: 10.1016/j.clnesp.2020.06.022
    BACKGROUND: Diabetes mellitus is a leading cause of preventable deaths and becomes a major public health concern in Malaysia. Multiple studies have reported the association between diet quality and glycemic parameters among known diabetic subjects. Its influence in individuals with borderline diabetes (i.e. pre-diabetes) or unknown diabetes is still unclear.

    OBJECTIVE: The objective of this study was to assess the association between diet quality evaluated by healthy eating index (HEI) with the glucose outcome in individuals with distinct diabetes progression stages, as well as to identify causal factors in relation to their diabetes status.

    METHOD: A cross-sectional study was conducted at clinical care setting in Universiti Sains Malaysia (USM) between October 2018-March 2019. Normoglycemic controls (n = 47), at-risk of pre-diabetes (n = 58), pre-diabetes (n = 24) as well as individuals with undiagnosed diabetes (n = 18) were queried about their habitual diet by using Food Frequency Questionnaire (FFQ). Correlation analyses were performed to examine the relationship between HEI score and 1) Fasting plasma glucose (FPG) 2) postprandial blood glucose (2-HPP) and glycosylated hemoglobin (HbA1c). Multinomial regression was performed to identify predictors associated with diabetes status of study participants.

    RESULT: Overall, diet quality of study participants was unsatisfactory with the mean score of 58.05 ± 9.07 that need improvement. Total HEI score was negatively correlated with the 2-HPP levels in pre-diabetic patients (r = - 0.45, p = 0.05). No significant association was revealed between glycemic parameters and total HEI score among other groups. Age, body mass index (BMI), triglycerides and female gender were positively correlated with the risk of pre-diabetes, at-risk of pre-diabetes and undiagnosed diabetes (p 

  13. Siddiqui S, Zainal H, Harun SN, Sheikh Ghadzi SM, Ghafoor S
    Diabetes Metab Syndr, 2020 07 08;14(5):1243-1252.
    PMID: 32688241 DOI: 10.1016/j.dsx.2020.06.069
    BACKGROUND: Prediabetes is a risk state for the future development of type 2 diabetes. Previously, it was evident that the risk factors for diabetes differ by gender. However, conclusive evidence regarding the gender difference in modifiable risk factors associated with the presence of pre-diabetes is still lacking.

    AIMS: To systematically identify and summarize the available literature on whether the modifiable risk factors associated with prediabetes displays similar relationship in both the genders.

    METHODS: A systematic search was performed on electronic databases i.e. PubMed, EBSCOhost, and Scopus using "sex", "gender", "modifiable risk factors" and "prediabetes" as keywords. Reference list from identified studies was used to augment the search strategy. Methodological quality and results from individual studies were summarized in tables.

    RESULTS: Gender differences in the risk factor association were observed among reviewed studies. Overall, reported association between risk factors and prediabetes apparently stronger among men. In particular, abdominal obesity, dyslipidemia, smoking and alcohol drinking habits were risk factors that showed prominent association among men. Hypertension and poor diet quality may appear to be stronger among women. General obesity showed stringent hold, while physical activity not significantly associated with the risk of prediabetes in both the genders.

    CONCLUSIONS: Evidence suggests the existence of gender differences in risk factors associated with prediabetes, demands future researchers to analyze data separately based on gender. The consideration and the implementation of gender differences in health policies and in diabetes prevention programs may improve the quality of care and reduce number of diabetes prevalence among prediabetic subjects.

  14. Harun SN, Ahmad H, Lim HN, Chia SL, Gill MR
    Pharmaceutics, 2021 Jan 24;13(2).
    PMID: 33498795 DOI: 10.3390/pharmaceutics13020150
    The ruthenium polypyridyl complex [Ru(dppz)2PIP]2+ (dppz: dipyridophenazine, PIP: (2-(phenyl)-imidazo[4,5-f ][1,10]phenanthroline), or Ru-PIP, is a potential anticancer drug that acts by inhibiting DNA replication. Due to the poor dissolution of Ru-PIP in aqueous media, a drug delivery agent would be a useful approach to overcome its limited bioavailability. Mesoporous silica nanoparticles (MSNs) were synthesized via a co-condensation method by using a phenanthrolinium salt with a 16 carbon length chain (Phen-C16) as the template. Optimization of the synthesis conditions by Box-Behnken design (BBD) generated MSNs with high surface area response at 833.9 m2g-1. Ru-PIP was effectively entrapped in MSNs at 18.84%. Drug release profile analysis showed that Ru-PIP is gradually released, with a cumulative release percentage of approximately 50% at 72 h. The release kinetic profile implied that Ru-PIP was released from MSN by diffusion. The in vitro cytotoxicity of Ru-PIP, both free and MSN-encapsulated, was studied in Hela, A549, and T24 cancer cell lines. While treatment of Ru-PIP alone is moderately cytotoxic, encapsulated Ru-PIP exerted significant cytotoxicity upon all the cell lines, with half maximal inhibitory concentration (IC50) values determined by MTT (([3-(4,5-dimethylthiazol-2-yl)-2,5-dephenyltetrazolium bromide]) assay at 48 h exposure substantially decreasing from >30 µM to <10 µM as a result of MSN encapsulation. The mechanistic potential of cytotoxicity on cell cycle distribution showed an increase in G1/S phase populations in all three cell lines. The findings indicate that MSN is an ideal drug delivery agent, as it is able to sustainably release Ru-PIP by diffusion in a prolonged treatment period.
  15. 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.

  16. Singh D, Narayanan S, Vicknasingam BK, Prozialeck WC, Ramanathan S, Zainal H, et al.
    J Psychoactive Drugs, 2018 03 20;50(3):266-274.
    PMID: 29558272 DOI: 10.1080/02791072.2018.1443234
    Kratom (Mitragyna speciosa Korth.) is traditionally used in Southeast Asia for its medicinal value and psychoactive properties. Nonetheless, cessation from regular kratom use is reported to cause unpleasant dose-dependent withdrawal symptoms. This study aims to evaluate the severity of pain and sleep problems following the cessation of kratom tea/juice consumption among regular kratom users. A total of 170 regular users were recruited through snowball sampling for this cross-sectional study. The Brief Pain Inventory (BPI) and Pittsburgh Sleep Quality Index (PSQI) scales were administered to assess the severity of pain and sleep problems. Most participants experienced moderate pain intensity (84%) and moderate pain interference (70%) during kratom cessation; 46% experienced more sleep problems during kratom cessation. Individuals who consumed ≥4 glasses of kratom tea/juice (about 76-115 mg of mitragynine) daily had higher odds of reporting some pain interference (OR: 2.0; CI: 1.04-3.93: p 
  17. 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.

  18. Elhefnawy ME, Sheikh Ghadzi SM, Tangiisuran B, Zainal H, Looi I, Ibrahim KA, et al.
    Int J Gen Med, 2021;14:1205-1212.
    PMID: 33854362 DOI: 10.2147/IJGM.S303641
    BACKGROUND AND PURPOSE: Factors associated with ischemic stroke (IS) recurrence and the contribution of pharmacological treatment as secondary preventions among nondiabetics especially in the non-elderly population are unclear and not widely investigated. This was a population-based study that aimed to identify recurrent IS predictors and to determine the possible impact of secondary preventive medications on the IS recurrence in non-elderly adults with or without diabetes.

    METHODS: Data of 3386 patients <60 years old who had a history of index IS were extracted from the Malaysian National Neurology Registry (NNEUR) from 2009 to 2016. Recurrent IS was defined as any IS event recorded after the index IS in the NNEUR database. Multivariate logistic regression analysis was performed by using SPSS version 22.

    RESULTS: Ischemic heart disease (IHD) was the significant predictor of IS recurrence in non-elderly adults both with or without diabetes (adjusted odds ratio (AOR) of 3.210; 95%CI: 1.909-5.398 and 2.989; 95%CI: 1.515-5.894) respectively). Receiving antiplatelet as secondary stroke prevention (AOR: 0.194; 95%CI: 0.046-0.817) and continuation of antidiabetic medication after the index IS event (AOR: 0.510; 95%CI: 0.298-0.872) reduced the odds of IS recurrence only in non-elderly diabetic adults. Among non-elderly adults without diabetes, hyperlipidemia and every increased in 1 mmHg of systolic blood pressure significantly increased the odds of IS recurrence following the indexing event (AOR: 1.796; 95%CI: 1.058-3.051 and 1.009; 95%CI: 1.002-1.016 respectively).

    CONCLUSION: IHD was found as the main predictor of IS recurrence regardless of diabetes status in non-elderly adults after the index IS event. Receiving antidiabetic and antiplatelet medications upon discharge after index IS were significant predictors of recurrent IS in non-elderly diabetic adults. A proper randomized clinical trial may be required to determine the impact of secondary preventive medication on IS recurrence, especially in non-elderly adults.

  19. Alrabadi N, Bany-Melhem S, Alzoubi KH, Alzoubi OO, Masadeh M, Abuhammad S, et al.
    PMID: 35549859 DOI: 10.2174/2772432817666220512112913
    Vaccines are important to improve immunity against pathogens and diseases. The current COVID-19 disease is rapidly evolving and spreading among people; therefore, it is important to utilize a proper vaccination strategy against it. Currently, many approved vaccines are available and accessible; however, there is a reported hesitancy against taking them among the public and even the health care workers. Mainly, this is attributed to the fear of the possible side effects and complications. Moreover, inaccurate knowledge disseminated through the media/social media especially by those who lack proper expertise adds confusion and more fear that affects the vaccination decision. For such reasons, it is essential to find strategies to increase the acceptability of vaccines and to enhance confidence in the vaccination process. This should be accompanied by sufficient efforts and proper clinical studies to confirm the value and the safety of the vaccines. Those strategies are important to avoid the further spread of the COVID-19 disease and to abort the pandemic worldwide, especially when considering the likely approach towards a COVID-19 booster vaccination program, in which booster vaccines are re-taken along intervals to adequately contain the rapidly evolving nature of the virus. This review article highlights the factors influencing the acceptability of the COVID-19 vaccination and enrollment in clinical trials among the public and some specific populations. Furthermore, it summarizes the suggested strategies and recommendations that can improve the attitudes towards COVID-19 vaccination programs.
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