Displaying publications 21 - 38 of 38 in total

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  1. Albitar O, Ghadzi SMS, Harun SN, Ahmad SNA, Kjellsson MC
    J Pharmacokinet Pharmacodyn, 2023 Feb;50(1):21-31.
    PMID: 36380133 DOI: 10.1007/s10928-022-09833-9
    Clozapine has superior efficacy to other antipsychotics yet is underutilized due to its adverse effects, such as neutropenia, weight gain, and tachycardia. The current investigation aimed to introduce a pharmacometric approach to simultaneously model drug adverse effects, with examples from schizophrenia spectrum patients receiving clozapine. The adverse drug effects were represented as a function of time by incorporating a mixture model to describe individual susceptibility to the adverse effects. Applications of the proposed method were presented by analyzing retrospective data from patients' medical records in Psychiatric Clinic, Penang General Hospital. Tachycardia, weight gain, and absolute neutrophils count (ANC) decrease were best described by an offset, a piecewise linear, and a transient surge function, respectively. 42.9% of the patients had all the adverse effects, including weight gain (0.01 kg/m2 increase every week over a baseline of 24.7 kg/m2 until stabilizing at 279 weeks), ANC decrease (20% decrease from 4540 cells/µL week 12-20.8), and tachycardia (14% constant increase over a baseline of 87.9 bpm for a clozapine maintenance dose of 450 mg daily). 32.5% of the patients had only tachycardia, while the remaining 24.6% had none of the adverse effects. A new pharmacometric approach was proposed to describe adverse drug effects with examples of clozapine-induced weight gain, ANC drop, and tachycardia. The current approach described the longitudinal time changes of continuous data while assessing patient susceptibility. Furthermore, the model revealed the possible co-existence of ANC drop and weight gain; thus, neutrophil monitoring might predict future changes in body weight.
  2. 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.
  3. Albitar O, Harun SN, Ballouze R, Mohamed Noor DA, Sheikh Ghadzi SM
    Ther Drug Monit, 2022 Apr 01;44(2):282-289.
    PMID: 34334682 DOI: 10.1097/FTD.0000000000000916
    BACKGROUND: Cyclosporine is an essential component of many immunosuppressive regimens. However, its pharmacokinetic and pharmacodynamic (PKPD) modeling has not been widely investigated. This study aims to develop a time-dissociated PKPD model of cyclosporine in renal transplant patients.

    METHODS: Medical records of renal transplant patients at Penang General Hospital were retrospectively analyzed. A time-dissociated PKPD model with covariate effects was developed using NONMEM to evaluate renal graft function response, quantified as estimated glomerular filtration rate (eGFR), toward the cyclosporine cumulative exposure (area under the concentration-time curve). The final model was integrated into a tool to predict the potential outcome. Individual eGFR predictions were evaluated based on the clinical response recorded as acute rejection/nephrotoxicity events.

    RESULTS: A total of 1256 eGFR readings with 2473 drug concentrations were obtained from 107 renal transplant patients receiving cyclosporine. An Emax drug effect with a linear drug toxicity model best described the data. The baseline renal graft level (E0), maximum effect (Emax), area under the concentration-time curve achieving 50% of the maximum effect, and nephrotoxicity slope were estimated as 12.9 mL·min-1·1.73 m-2, 50.7 mL·min-1·1.73 m-2, 1740 ng·h·mL-1, and 0.00033, respectively. The hemoglobin level was identified as a significant covariate affecting the E0. The model discerned acute rejection from nephrotoxicity in 19/24 cases.

    CONCLUSIONS: A time-dissociated PKPD model successfully described a large number of observations and was used to develop an online tool to predict renal graft response. This may help discern early rejection from nephrotoxicity, especially for patients unwilling to undergo a biopsy or those waiting for biopsy results.

  4. Mustafa ZU, Khan AH, Salman M, Harun SN, Meyer JC, Godman B, et al.
    J Hosp Infect, 2023 Nov;141:142-151.
    PMID: 37774930 DOI: 10.1016/j.jhin.2023.09.011
    BACKGROUND: Healthcare-associated infections (HAIs) increase morbidity, mortality and costs. The overall prevalence of HAIs is greater in low- and middle-income countries due to poor resources and infrastructure, with the incidence of HAIs greater among neonates and children. There is a need to understand the current situation in Pakistan including key drivers to improve future care.

    METHODS: Point prevalence survey (PPS) of HAIs in the children's wards of 19 public sector secondary- and tertiary-care hospitals of Pakistan and associated key drivers.

    RESULTS: A total of 1147 children were included in the PPS. 35.7% were neonates with 32.8% aged >1-5 years. 35.2% were admitted to the intensive care units (ICUs). Peripheral, central venous and urinary catheters were present in 48%, 2.9% and 5.6% of the patients, respectively. A total of 161 HAIs from various pathogens were observed in 153 cases, giving a prevalence of 13.3%. The majority of HAIs were caused by Staphylococcus aureus (31.7%) followed by Klebsiella pneumoniae (22.9%) and Escherichia coli (17.4%). Bloodstream infections were identified in 42 cases followed by lower-respiratory-tract infections in 35. Increased length of hospital stays and being admitted to the ICU, 'rapidly fatal' patients under the McCabe and Jackson criteria, central and peripheral catheterization, and invasive mechanical ventilation were, associated with higher HAIs (P<0.001). 99.7% of HAI patients fully recovered and were discharged from the hospital.

    CONCLUSION: There is a high prevalence of HAIs among neonates and children admitted to health facilities in Pakistan. Infection prevention and control measures should be implemented to help prevent future HAIs.

  5. Siddiqui S, Harun SN, Ghadzi SMS, Wahid NA, Hassan AB, Zainal H
    PMID: 38213389 DOI: 10.51866/oa.125
    INTRODUCTION: Diabetes is closely linked to cardiovascular diseases, with diabetic dyslipidaemia serving as an established marker of the acceleration of complications, contributing to an increased cardiovascular risk among patients. Timely detection and early characterization of lipid abnormalities can help clinicians in implementing effective preventive measures. This study aimed to determine the patterns and associated factors of dyslipidaemia among Malaysian subjects with borderline diabetes.

    METHODS: A retrospective study was conducted among subjects with borderline diabetes aged ≥18 years who visited a primary healthcare centre at Universiti Sains Malaysia from January 2017 to December 2018. Sociodemographic, clinical and laboratory data were obtained from electronic medical records. Data were analysed using SPSS version 25.

    RESULTS: A total of 250 participants with borderline diabetes were included in the analysis. Of them, 93.6% (n=234) had lipid abnormalities. Isolated dyslipidaemia characterised by a high low-density lipoprotein cholesterol (LDL-C) level (38.8%, n=97) was the most common pattern found, followed by combined dyslipidaemia of high LDL-C and triglyceride (TG) levels (22.8%, n=57). The male sex was found to be significantly associated with hypertriglyceridemia (adjusted odds ratio [AOR] = 1.86, 95% confidence interval [CI] =1.09-3.1)(P=0.02). Diastolic blood pressure ≥90mmHg was significantly associated with a low HDL-C level (A0R=2.09, 95% CI=1.0-4.1) (P=0.03).

    CONCLUSION: The majority of subjects with borderline diabetes have lipid abnormalities. Specifically, isolated dyslipidaemia characterised by a high LDL-C level is alarmingly prevalent. Further large-scale robust studies are needed to confirm the present findings.

  6. 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.
  7. Phaisal W, Albitar O, Chariyavilaskul P, Jantarabenjakul W, Wacharachaisurapol N, Ghadzi SMS, et al.
    PMID: 38661209 DOI: 10.1093/jac/dkae059
    OBJECTIVES: Twelve weekly doses of rifapentine and isoniazid (3HP regimen) are recommended for TB preventive therapy in children with TB infection. However, they present with variability in the pharmacokinetic profiles. The current study aimed to develop a pharmacokinetic model of rifapentine and isoniazid in 12 children with TB infection using NONMEM.

    METHODS: Ninety plasma and 41 urine samples were collected at Week 4 of treatment. Drug concentrations were measured using a validated HPLC-UV method. MassARRAY® SNP genotyping was used to investigate genetic factors, including P-glycoprotein (ABCB1), solute carrier organic anion transporter B1 (SLCO1B1), arylacetamide deacetylase (AADAC) and N-acetyl transferase (NAT2). Clinically relevant covariates were also analysed.

    RESULTS: A two-compartment model for isoniazid and a one-compartment model for rifapentine with transit compartment absorption and first-order elimination were the best models for describing plasma and urine data. The estimated (relative standard error, RSE) of isoniazid non-renal clearance was 3.52 L·h-1 (23.1%), 2.91 L·h-1 (19.6%), and 2.58 L·h-1 (20.0%) in NAT2 rapid, intermediate and slow acetylators. A significant proportion of the unchanged isoniazid was cleared renally (2.7 L·h-1; 8.0%), while the unchanged rifapentine was cleared primarily through non-renal routes (0.681 L·h-1; 3.6%). Participants with the ABCB1 mutant allele had lower bioavailability of rifapentine, while food prolonged the mean transit time of isoniazid.

    CONCLUSIONS: ABCB1 mutant allele carriers may require higher rifapentine doses; however, this must be confirmed in larger trials. Food did not affect overall exposure to isoniazid and only delayed absorption time.

  8. Al-Ashwal FY, Syed Sulaiman SA, Sheikh Ghadzi SM, Harun SN, Halboup A, Kubas MA
    Adv Med Educ Pract, 2024;15:357-368.
    PMID: 38707544 DOI: 10.2147/AMEP.S445610
    INTRODUCTION: Understanding the latest guideline recommendations is crucial for healthcare professionals to apply statin therapy effectively. Thus, the purpose of this study was to evaluate the efficacy of an educational intervention in enhancing the awareness and understanding of physicians and pharmacists concerning risk assessment of Atherosclerotic cardiovascular disease (ASCVD) and the role of statin therapy.

    METHODS: This pre- and post-intervention study was conducted in Sana'a, Yemen's capital city, at the University of Science and Technology Hospital. The study was done between 11/2021-12/2021, and two separate educational sessions were ‎held. The McNemar's test and Wilcoxon signed-rank test were employed as necessary.

    RESULTS: Participants' awareness of the Framingham CVD risk calculator improved significantly from 40.4% pre-intervention to 78.7% post-intervention. Similarly, understanding of the parameters used in the 10-year ASCVD Risk calculator rose from 46.8% pre-intervention to 76.6% post-intervention. The ability to identify high, moderate, and low-intensity statin therapy, for instance, increased from 34% to 63.8% post-intervention. Regarding statins' contraindications, safety, and efficacy monitoring parameters, pre-intervention knowledge was unsatisfactory, and the educational intervention improved it significantly (p <0.05). For physicians, the median ASCVD risk assessment knowledge score was significantly improved from ‎‎4 (IQR = 3-5) pre-intervention to 7 (6.25-8) immediately post-intervention, while the statin therapy clinical knowledge median score ‎significantly improved from 3 (1.25-6.5) to 9 (7.25-14.75) post-education intervention, p-values were 0.002 and 0.003; respectively. For pharmacists, a similar significant improvement (p <0.05) in the overall knowledge scores for both ASCVD risk ‎assessment and statin therapy was noted.

    CONCLUSION: The educational intervention improved participants' knowledge of statin therapy and ASCVD risk assessment. Therefore, further education lectures and training programs through continuing ‎medical ‎education on the up-to-date guidelines' recommendations should be regularly implemented to raise ‎awareness and improve ‎the clinical knowledge and appropriateness of statins use in clinical settings.‎.

  9. Javed S, Mohamed Noor DA, Md Hanafiah NH, Javed U, Mustafa T, Rehman AU, et al.
    J Surg Res, 2024 May 07;299:85-93.
    PMID: 38718688 DOI: 10.1016/j.jss.2024.04.001
    INTRODUCTION: The relationship between type 2 diabetes mellitus (T2DM) and pathological responses after neoadjuvant chemotherapy (NACT) is controversial. In this study, we aim to determine the association of pathological responses in breast cancer women with T2DM after receiving NACT.

    METHODS: Medical records of breast cancer women with T2DM who received NACT from January 2016 to January 2021 at the medical center in the Gujranwala Institute of Nuclear Medicine and Radiotherapy, Pakistan, were identified and retrieved retrospectively. Variables, including pathological responses, diabetes status, and other clinical data, were collected. Patients were grouped as diabetic and nondiabetic based on the doctor's diagnosis or the diabetic's medication history recorded upon the breast cancer diagnosis. Factors influencing the pathological complete response (pCR) were determined using multivariate logistic regression utilizing IBM SPSS Statistics (version 20).

    RESULTS: A total of 1372 patient files who received NACT and breast cancer surgery from January 2016 to January 2021 were selected. Out of 1372 breast cancer women receiving NACT, 345 (25.1%) had pre-existing diabetes, while 1027 (74.85%) were without pre-existing diabetes. The most common molecular subtypes of breast cancer were luminal A and B. Two hundred fifty-eight patients (18.8%) had a pCR after receiving NACT. The pCR in diabetic patients was 3.9%, and in nondiabetes, 14.9%. Most women had a pathological partial response (pPR) after the NACT 672 (48.9%). The pPR in diabetic patients was 11.0%, and in nondiabetic patients, it was 38.0%. In nondiabetics, the odds of achieving pPR increase more than pathological no response after the NACT with odd ratio: 1.71 (95% confidence interval: 1.24-2.37). The probability of pCR in patients with luminal B was 1.67 times higher than that in patients with triple-negative breast cancer with odd ratio: 1.67, 95% confidence interval (1.00-2.79), P = 0.05.

    CONCLUSIONS: The results of the study show that T2DM may have an adverse impact on pCR and pPR following NACT and surgery. Further investigation is needed to explore how changes in blood glucose levels over time impact pathological responses.

  10. 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.
  11. 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.

  12. Rehman AU, Shah S, Abbas G, Harun SN, Shakeel S, Hussain R, et al.
    Sci Rep, 2021 Jun 30;11(1):13578.
    PMID: 34193949 DOI: 10.1038/s41598-021-92968-5
    Compromised lung function is a common feature of COPD patients, but certain factors increase the rate of lung function decline in COPD patients. The objective of the current study was to investigate the effect of different clinically important factors responsible for rapid deterioration of lung function quantified as ≥ 60 ml decline in FEV1 over a period of one year. COPD patients recruited from the chest clinic of Penang hospital were followed-up for one year from August 2018 to August 2019. Rapid deterioration of lung function was defined as greater than 60 ml/year decline in force expiratory volume in one second. Among 367 included patients 73.84% were male, with mean age 65.26 (9.6) years and % predicted FEV1 51.07 (11.84). 30.27% patients showed mean decline of ≥ 60 ml in FEV1. The regression analysis showed that current smoking relative risk (RR) = 2.38 (1.78-3.07), p 
  13. 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.

  14. 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.

  15. 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.
  16. 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.

  17. 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.

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