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Fulltext Health-related quality of life of patients with multidrug-resistant tuberculosis in Yemen: prospective study

Jaber AAS, Ibrahim B

Health Qual Life Outcomes, 2019 Aug 16;17(1):142.
PMID: 31420045 DOI: 10.1186/s12955-019-1211-0

BACKGROUND: Substantial efforts are currently focused on investigating and developing new multidrug-resistant tuberculosis (MDR-TB) drugs and diagnostic methods. In Yemen, however, the evaluation of health-related quality of life (HRQoL) and the effect of current MDR-TB treatment on the QoL are commonly ignored. This study evaluated the HRQoL during and after treatment and identified the risk factors that are predictive of HRQoL score differences.
METHOD: A prospective cohort study was conducted in four of the five main MDR-TB centres in Yemen. The patients confirmed with MDR-TB completed the SF-36 V2 survey at the beginning of treatment, end of treatment (continous phase) and at the 1 year follow-up after completing treatment. A total normal base score (NBS) of
Fulltext Evaluation of risk factors associated with drug-resistant tuberculosis in Yemen: data from centres with high drug resistance

Jaber AAS, Ibrahim B

BMC Infect Dis, 2019 May 24;19(1):464.
PMID: 31126246 DOI: 10.1186/s12879-019-4069-1

BACKGROUND: The World Health Organization (WHO) has reported that Yemen has a high burden of drug resistance and a worrying shortage of implemented diagnostic methods and drug treatment regimens. Therefore, in this study, we evaluated the risk factors associated with multidrug-resistant tuberculosis (MDR-TB) and explored the poor TB management in Yemen.
METHODS: Between January 2014 and December 2016, we enrolled 135 patients with MDR-TB from drug resistance programmes at four major TB centres in Yemen for this prospective study. After exclusion of 20 patients, treatment outcomes were reported for 115 patients who attended a series of follow-ups.
RESULTS: A total of 115 patients with MDR-TB were analysed from the four main TB centres in Yemen. Most patients (35.2%) were from the Aden TB centre. A success rate of 77.4% was reported for TB treatment. Of the 115 patients, 69.6% were resistant to two drugs, 18.3% were resistant to three drugs, and 12.2% were resistant to four drugs. During the intensive phase of treatment, 19 patients (16.5%) reported one or more adverse events. A multivariate logistic regression analysis revealed that a baseline body weight of ≤40 kg [p = 0.016; adjusted odds ratio (AOR) = 25.09], comorbidity (p = 0.049; AOR = 4.73), baseline lung cavities (p = 0.004; AOR = 15.32), and positive culture at the end of the intensive phase (p = 0.009; AOR = 8.83) were associated with the unsuccessful treatment outcomes in drug-resistant TB patients.
CONCLUSIONS: The success rate achieved after treatment was below the levels established by the WHO End TB Strategy (90%) and the United Nations Sustainable Development Goals (80%). Identification of risk factors associated with MDR-TB in Yemen is essential because it allows health workers to identify high-risk patients, especially in the absence of a second-line treatment or a laboratory diagnostic method. The Yemen National Tuberculosis Control Program should formulate new strategies for early detection of MDR-TB and invest in new programmes for MDR-TB management.
Urinary metabolites of type 2 diabetes rats fed with palm oil-enriched high fat diet

Sim XY, Ibrahim B, Gam LH

Heliyon, 2021 Sep;7(9):e08075.
PMID: 34632142 DOI: 10.1016/j.heliyon.2021.e08075

High fat diet (HFD) is one of the risk factors of obesity and diabetes. Recommended diet regimen for diabetes is difficult to abide by especially for HFD as it adds flavour to the taste buds. In this study, palm oil-enriched HFD and normal diet were fed to nicotinamide-induced type 2 diabetes rats, respectively for six weeks. Additionally, metformin, a common drug used to treat diabetes was given to rats under treatment groups. We evaluated the change of urinary metabolites of diabetes rats fed with palm oil-enriched HFD, and also after metformin treatment. Rats were divided into six-groups with different feeding diets, disease condition and with or without metformin treatment. Rats' urine were collected at the end of six weeks feeding program and subjected to 1H-NMR and multivariate data analysis to evaluate their metabolite profiles. At the early phase of diabetes, metabolites changes in diabetic rats were associated with the disease itself. Our data showed that continuous consumption of HFD altered various metabolic pathways of diabetic rats and caused detrimental effects to the rats. On the other hand, metformin treatment combined with normal diet lessened the physiological impacts caused by diabetes condition.
Statin therapy for patients with diabetic nephropathy: balance between safety and efficacy of statin treatment for patients with impaired kidney function

Jairoun AA, Ping CC, Ibrahim B

Eur Rev Med Pharmacol Sci, 2023 Nov;27(21):10595-10604.
PMID: 37975384 DOI: 10.26355/eurrev_202311_34339

The International Diabetes Federation estimates that by 2035, there will be 592 million people with diabetes worldwide, substantially increasing from the 382 million patients with diabetes recorded in 2013. Diabetes-related nephropathy is a leading cause of end-stage renal disease. Recently, the therapeutic use of statins in patients with chronic kidney disease (CKD) was explored in a series of meta-analyses, which revealed their potential for decreasing mortality and cardiovascular complications in this population, although not in patients undergoing hemodialysis. The current study reviews the current state of knowledge on statin therapy regarding its safety and efficacy concerning renal outcomes in diabetic patients with CKD. The evidence shows that statins may offer a beneficial renoprotective effect in inhibiting the progression of renal function decline. This effect is time-dependent and particularly strong in patients with type 2 diabetes and nephropathy. In addition, whether certain statin types are more beneficial than others in slowing renal function loss and reducing proteinuria remains unclear. Prior research has not examined the impact of high-intensity statin therapy on CKD patient outcomes.
Fulltext Pharmacotherapeutic considerations and treatment patterns of antihyperglycemic agents for diabetic nephropathy: a review of the literature

Jairoun AA, Ping CC, Ibrahim B

Eur Rev Med Pharmacol Sci, 2023 Dec;27(24):12058-12069.
PMID: 38164868 DOI: 10.26355/eurrev_202312_34804

Diabetes can have several macrovascular and microvascular complications in addition to diabetic nephropathy, also referred to as diabetic kidney disease (DKD). DKD is found to occur in approximately 40% of patients with type 2 diabetes and 30% of patients with type 1 diabetes. However, research on the effects of antihyperglycemic agents on the renal outcomes of these patients is still in its infancy. The current review explores glycemic management in patients with DKD, focusing on the challenges faced as well as the clinical considerations of antihyperglycemic agents in this population. A comprehensive literature review was conducted using EMBASE, Web of Science, and PubMed databases. This review was completed by the end of March 2023, and the following keywords were used for the search: diabetic nephropathy, diabetic kidney disease, safety, efficacy, and antihyperglycemic therapies. The several concerns about the use of antihyperglycemic agents in treating diabetes in patients with DKD highlight the need for substantial efforts in educating both patients and healthcare practitioners in this regard. In addition, it is suggested that patients receive individualized treatments, considering the potential long-term benefits of each agent; this would entail prospectively modifying doses in line with the stage of DKD to prevent the progression of renal damage. As some classes of agents offer better renoprotective effects for patients with DKD, it would be wise for nephrologists and endocrinologists to collaborate to offer an antihyperglycemic regime for patients with DKD who are at a high risk of further progression. Further study is needed on the beneficial renal effects of specific classes of agents; more knowledge of their mechanisms and renoprotective effects may contribute to the development of novel treatments for patients with DKD.
Predictors of chronic kidney disease survival in type 2 diabetes: a 12-year retrospective cohort study utilizing estimated glomerular filtration rate

Jairoun AA, Ping CC, Ibrahim B

Sci Rep, 2024 Apr 19;14(1):9014.
PMID: 38641627 DOI: 10.1038/s41598-024-58574-x

Predicting the course of kidney disease in individuals with both type 1 and type 2 diabetes mellitus (DM) is a significant clinical and policy challenge. In several regions, DM is now the leading cause of end-stage renal disease. The aim of this study to identify both modifiable and non-modifiable risk factors, along with clinical markers and coexisting conditions, that increase the likelihood of stage 3-5 chronic kidney disease (CKD) development in individuals with type 2 DM in the United Arab Emirates (UAE). This was a single-center retrospective cohort study based on data derived from electronic medical records of UAE patients with DM who were registered at outpatient clinics at Tawam Hospital in Al Ain, UAE, between January 2011 and December 2021. Type 2 DM patients aged ≥ 18 years who had serum HbA1c levels ≥ 6.5% were included in the study. Patients with type 1 DM, who had undergone permanent renal replacement therapy, who had under 1 year of follow-up, or who had missing or incomplete data were excluded from the study. Factors associated with diabetic patients developing stage 3-5 CKD were identified through Cox regression analysis and a fine and gray competing risk model to account for competing events that could potentially hinder the development of CKD. A total of 1003 patients were recruited for the study. The mean age of the study cohort at baseline was 70.6 ± 28.2 years. Several factors were found to increase the risk of developing stage 3-5 CKD: advancing age (HR 1.005, 95% CI 1.002-1.009, p = 0.026), a history of hypertension (HR 1.69, 95% CI 1.032-2.8, p = 0.037), a history of heart disease (HR 1.49, 95% CI 1.16-1.92, p = 0.002), elevated levels of serum creatinine (HR 1.006, 95% CI 1.002-1.010, p = 0.003), decreased levels of estimated glomerular filtration rate (eGFR) (HR 0.943, 95% CI, 0.938-0.947; p
What do healthcare providers know about nutrition support? A survey of the knowledge, attitudes, and practice of pharmacists and doctors toward nutrition support in Malaysia

Karim SA, Ibrahim B, Tangiisuran B, Davies JG

JPEN J Parenter Enteral Nutr, 2015 May;39(4):482-8.
PMID: 24590009 DOI: 10.1177/0148607114525209

Malnutrition is one of the health problems that can be prevented by appropriate nutrition care provided by healthcare providers. However, this practice is still lacking possibly because of the providers' inadequate knowledge. The aim of this study was to evaluate the self-reported knowledge, attitudes, and practices of pharmacists and doctors toward nutrition support in a tertiary care hospital setting.
Fulltext VitalQPlus: a potential screening tool for early diagnosis of COPD

Sui CF, Ming LC, Neoh CF, Ibrahim B

Int J Chron Obstruct Pulmon Dis, 2015;10:1613-22.
PMID: 26316735 DOI: 10.2147/COPD.S84618

Background: This study utilized a validated combination of a COPD Population Screener
(COPD-PS) questionnaire and a handheld spirometric device as a screening tool for patients at high risk of COPD, such as smokers. The study aimed to investigate and pilot the feasibility and application of this combined assessment, which we termed the “VitalQPlus”, as a screening tool for the early detection of COPD, especially in primary care settings.
Methods: This was a cross-sectional study screening potentially undiagnosed COPD patients using a validated five-item COPD-PS questionnaire together with a handheld spirometric device. Patients were recruited from selected Malaysian government primary care health centers.
Results: Of the total of 83 final participants, only 24.1% (20/83) were recruited from Perak and Penang (peninsular Malaysia) compared to 75.9% (63/83) from Sabah (Borneo region). Our dual assessment approach identified 8.4% of the surveyed patients as having potentially undiagnosed COPD. When only the Vitalograph COPD-6 screening tool was used, 15.8% of patients were detected with a forced expiratory volume in 1 second/forced expiratory volume in 6 seconds (FEV1/FEV6) ratio at <0.75, while 35.9% of patients were detected with the COPD-PS questionnaire. These findings suggested that this dual assessment approach has a greater chance of identifying potentially undiagnosed COPD patients compared to the Vitalograph COPD-6 or COPD-PS questionnaire when used alone. Our findings show that patients with more symptoms (scores of >=5) yielded twice the percentage of outcomes of FEV1/FEV6 <0.75 compared to patients with fewer COPD symptoms (scores <5).
Conclusion: With the availability of a simple screening questionnaire and the COPD-6, there is an opportunity easily to make patients more aware of their lung symptoms and to encourage the provision of early treatment. The proposed dual assessment approach, which we termed the VitalQPlus, may play a profound role in the early diagnosis of COPD, which is crucial in improving the clinical management of the disease.
Keywords: spirometry, pulmonary function test, chronic obstructive pulmonary disease,
airway obstruction
Urinary NMR-based metabolomic analysis of rats possessing variable sperm count following orally administered Eurycoma longifolia extracts of different quassinoid levels

Ebrahimi F, Ibrahim B, Teh CH, Murugaiyah V, Chan KL

J Ethnopharmacol, 2016 Apr 22;182:80-9.
PMID: 26899442 DOI: 10.1016/j.jep.2016.02.015

Eurycoma longifolia (Tongkat Ali, TA) roots have been ethnically used as a remedy to boost male sexual desire, libido, energy and fertility.
Effects of the ABCB1 C3435T single nucleotide polymorphism on major adverse cardiovascular events in acute coronary syndrome or coronary artery disease patients undergoing percutaneous coronary intervention and treated with clopidogrel: A systematic review and meta-analysis

Biswas M, Rahaman S, Biswas TK, Ibrahim B

Expert Opin Drug Saf, 2020 Dec;19(12):1605-1616.
PMID: 33040624 DOI: 10.1080/14740338.2020.1836152

INTRODUCTION: The effects of the ABCB1 C3435T genetic polymorphism on clopidogrel responses are conflicting and inconclusive especially in patients undergoing percutaneous coronary intervention (PCI). This study examined the pooled risk of major adverse cardiovascular events (MACE) and bleeding events associated with the ABCB1 C3435T polymorphism in acute coronary syndrome or coronary artery disease patients undergoing PCI and treated with clopidogrel.
AREAS COVERED: Literature was searched in different resources for eligible studies. The pooled risk ratio was measured using RevMan software, with p<0.05 (two-sided) set as statistically significant.
EXPERT OPINION: The ABCB1 C3435T homozygous mutant (TT) was associated with significantly increased risk of MACE compared to either wild type genotype (CC) or the combination of wild type and heterozygous genotypes (TT vs. CC: RR 1.33; 95% CI 1.06-1.68; p=0.02; TT vs. CC+CT: RR 1.32; 95% CI 1.10-1.60; p=0.004). Safety outcomes, i.e. bleeding events were not significantly different between the genetic models investigated (TT vs. CC: RR 1.93; 95% CI 0.86-4.35; p=0.11; TT vs. CC+CT: RR 1.36; 95% CI 0.89-2.09; p=0.16; CT+TT vs. CC: RR 1.20; 95% CI 0.59-2.44; p=0.61). It is suggested that ABCB1 C3435T genotype should be tested for ACS/CAD patients undergoing PCI to ensure optimum therapy of clopidogrel.
Addressing the standardisation of internal standards and preservative used in human bio fluids for NMR analysis: a method optimization

Abd Aziz F, Ibrahim B, Murugaiyah V, Sarriff A

Drug Metab Pers Ther, 2021 Mar 04;36(3):189-197.
PMID: 34412173 DOI: 10.1515/dmpt-2020-0154

OBJECTIVES: A database comprising multivariate data in developing a model from nuclear magnetic resonance (NMR) analysis using human bio fluids are necessary to have reproducibility and reliability of the data. To achieve reproducibility of the data, standardised experiments, including internal standard and preservative used should be attained, especially for samples such as human bio fluids to hinder the variation among samples. The aim of the study was to optimise in commonly used human bio fluids (serum and urine) for a suitable internal standard and preservative used in extended storage samples for NMR analysis.
METHODS: Serum and urine samples were collected from healthy human subjects. The experiment was divided into two parts, part one to evaluate 2,2,2,2-tetradeutero-4,4-dimethyl-4-silapentanoic acid (TSP) and 4,4-dimethyl-4-silapentane-1-ammonium trifluoroacetate (DSA) as the optimal internal standard for the serum and urine samples. The second part investigated the effects of preservatives in the serum and urine samples on extended storage.
RESULTS: Overall, TSP and DSA are suitable to be used as an internal standard in human urine samples. However, DSA is a superior internal standard in serum samples for NMR analysis. For the effect of preservative, the results indicated that human serum and urine samples could be stored without addition of preservative in -80 °C, as no changes in NMR fingerprinting have been observed during storage in the absence or presence of the preservative.
CONCLUSIONS: The findings suggest the use of DSA and TSP as an internal standard in serum and urine samples, respectively. Storage of serum and urine samples without any addition of preservative for an extended period has no effect on the metabolites changes. By having a standardised method, it will offer a considerable saving in both operator and spectrometer time and most importantly produce reproducible and reliable data.
Cardiovascular risk factors of Alzheimer's disease and other neurocognitive disorders in Malaysia

Ibrahim B, Suppiah S, Piersson AD, Razali RM, Mohamad M, Abu Hassan H, et al.

Med J Malaysia, 2021 05;76(3):291-297.
PMID: 34031325

INTRODUCTION: Risk factors for cardiovascular disease (CVD) have been increasingly implicated in the development of dementia but little is known about the effects in a Malaysian population. We aimed to determine the interaction between sociodemographic and CVD risk factors among the dementia and mild cognitive impairment (MCI) patients in Malaysia.
MATERIALS AND METHODS: A cross-sectional study was conducted in the memory clinic at Hospital Kuala Lumpur (HKL). Medical records data from 2014 to 2019 were extracted. Mini Mental State Examination (MMSE) test was used to assess the neurocognitive function of patients.
RESULTS: A total of 298 patients (30 MCI, and 268 dementia) were evaluated, with dementia patients consisting of 78 Alzheimer's disease (AD), 93 Vascular dementia (VaD), 94 Mixed dementia, 2 early-onset Alzheimer's disease (EOAD) and 1 Logopenic Progressive Aphasia type of AD (LPA). MCI and dementia were significantly associated with a history of CVD, particularly stroke (p=0.023).
CONCLUSION: Given that stroke significantly predicted the risk of developing vascular dementia among the patients in a central Malaysian population, lifestyle modifications are recommended to alleviate these risk factors of CVD.
Risk of major adverse cardiovascular events for concomitant use of clopidogrel and proton pump inhibitors in patients inheriting CYP2C19 loss-of-function alleles: meta-analysis

Biswas M, Rahaman S, Biswas TK, Ibrahim B

Int J Clin Pharm, 2021 Oct;43(5):1360-1369.
PMID: 33774763 DOI: 10.1007/s11096-021-01261-y

Background Efficacy of clopidogrel may be diminished due to either co-administration of proton pump inhibitors or carrying CYP2C19 loss-of-function alleles. However, patients may be at greater risk of major adverse cardiovascular events if taking clopidogrel together with proton pump inhibitors and also inherited the CYP2C19 loss-of-function alleles which may cause further reduction of clopidogrel efficacy. This is due to the cumulative effects of drug-drug interactions and drug-gene interactions collectively referred to as multifactorial drug-gene interactions. Aim of the review The aim of this analysis was to estimate aggregated risk of major adverse cardiovascular events for either coronary heart disease or stroke patients with multifactorial drug-gene interactions versus clopidogrel alone with or without drug-gene interactions. Methods Literatures were searched using different resources based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Meta-analysis was performed using RevMan software following either fixed/random effects model based on the levels of heterogeneity. A p value
NMR-based plasma metabolomic discrimination for male fertility assessment of rats treated with Eurycoma longifolia extracts

Ebrahimi F, Ibrahim B, Teh CH, Murugaiyah V, Chan KL

Syst Biol Reprod Med, 2017 Jun;63(3):179-191.
PMID: 28306342 DOI: 10.1080/19396368.2017.1295332

Male infertility is one of the leading causes of infertility which affects many couples worldwide. Semen analysis is a routine examination of male fertility status which is usually performed on semen samples obtained through masturbation that may be inconvenient to patients. Eurycoma longifolia (Tongkat Ali, TA), native to Malaysia, has been traditionally used as a remedy to boost male fertility. In our recent studies in rats, upon the administration of high-quassinoid content extracts of TA including TA water (TAW), quassinoid-rich TA (TAQR) extracts, and a low-quassinoid content extract including quassinoid-poor TA (TAQP) extract, sperm count (SC) increased in TAW- and TAQR-treated rats when compared to the TAQP-treated and control groups. Consequently, the rats were divided into normal- (control and TAQP-treated) and high- (TAW- and TAQR-treated) SC groups [Ebrahimi et al. 2016]. Post-treatment rat plasma was collected. An optimized plasma sample preparation method was developed with respect to the internal standards sodium 3- (trimethylsilyl) propionate- 2,2,3,3- d4 (TSP) and deuterated 4-dimethyl-4-silapentane-1-ammonium trifluoroacetate (DSA). Carr-Purcell-Meibum-Gill (CPMG) experiments combined with orthogonal partial least squares discriminant analysis (OPLS-DA) was employed to evaluate plasma metabolomic changes in normal- and high-SC rats. The potential biomarkers associated with SC increase were investigated to assess fertility by capturing the metabolomic profile of plasma. DSA was selected as the optimized internal standard for plasma analysis due to its significantly smaller half-height line width (W h/2) compared to that of TSP. The validated OPLS-DA model clearly discriminated the CPMG profiles in regard to the SC level. Plasma profiles of the high-SC group contained higher levels of alanine, lactate, and histidine, while ethanol concentration was significantly higher in the normal-SC group. This approach might be a new alternative applicable to the fertility assessment in humans through the quantitative metabolomic analysis of plasma without requiring semen.
ABBREVIATIONS: TA: Tongkat Ali; LOD: limit of detection; LOQ: limit of quantification; HPLC-UV: high performance liquid chromatography-ultrviolet; PDA: photodiode array; NMR: nuclear magnetic resonance; FID: free induction decay; LC-MS: liquid chromatography-mass spectrometry; GC-MS: gas chromatography-mass spectrometry; HSQC: heteronuclear single quantum coherence; CPMG: Carr-Purcell-Meibum-Gill; VLDL: very low density lipoprotein; HDL: high density lipoprotein; EDTA: ethylenediaminetetraacetic acid; ANOVA: analysis of variance; AMIX: analysis of mixtures; SIMCA: soft independent modeling of class analogy; PCA: principal components analysis; OPLS-DA: orthogonal partial least-squares discriminant analysis; VIP: variable importance plot; AUROC: area under the receiver operating characteristic; TSP: sodium 3-(trimethylsilyl) propionate- 2,2,3,3- d4; DSA: deuterated 4-dimethyl-4-silapentane-1-ammonium trifluoroacetate; ESI: electrospray ionization; TCA: trichloroacetic acid; ACN: acetonitrile; dd H2O: distilled deionized water; FSH: follicle-stimulating hormone; LH: luteinizing hormone; OECD: Organisation for Economic Co-operation and Development.
The effectiveness of the McIsaac clinical decision rule in the management of sore throat: an evaluation from a pediatrics ward

Thillaivanam S, Amin AM, Gopalakrishnan S, Ibrahim B

Pediatr Res, 2016 Oct;80(4):516-20.
PMID: 27331353 DOI: 10.1038/pr.2016.113

BACKGROUND: Sore throats may be due to either viral or group A beta hemolytic streptococcus (GABHS) infections; but diagnosis of the etiology of a sore throat is difficult, often leading to unnecessary antibiotic prescriptions and consequent increases in bacterial resistance. Scoring symptoms using the McIsaac clinical decision rule can help physicians to diagnose and manage streptococcal infections leading to sore throat and have been recommended by the Ministry of Health, Malaysia. In this paper, we offer the first assessment of the effectiveness of the McIsaac rule in a clinical setting in Malaysia.
METHOD: This study is a retrospective review of 116 pediatric patients presenting with sore throat. Group A comprised patients before the implementation of the McIsaac rule and Group B comprised patients after the implementation.
RESULTS: Unnecessary throat swab cultures were reduced by 40% (P = 0.003). Redundant antibiotic prescriptions were reduced by 26.5% (P = 0.003) and the overall use of antibiotics was reduced by 22.1% (P = 0.003). The pediatricians' compliance rate to McIsaac rule criteria was 45% before implementation of the McIsaac rule, but improved to 67.9% (P = 0.0005) after implementation.
DISCUSSION: The McIsaac rule is an effective tool for the management of sore throat in children in Malaysia.
Risk of major adverse cardiovascular events of CYP2C19 loss-of-function genotype guided prasugrel/ticagrelor vs clopidogrel therapy for acute coronary syndrome patients undergoing percutaneous coronary intervention: a meta-analysis

Biswas M, Kali MSK, Biswas TK, Ibrahim B

Platelets, 2021 Jul 04;32(5):591-600.
PMID: 32664772 DOI: 10.1080/09537104.2020.1792871

The most effective antiplatelet treatments for acute coronary syndrome (ACS) patients carrying CYP2C19 loss-of-function (LoF) alleles undergoing percutaneous coronary intervention (PCI) is still debating and conflicting. It was aimed to compare the efficacy and safety endpoints for these patients treated with alternative P2Y12 receptor blockers (e.g. prasugrel or ticagrelor) against clopidogrel. Literature was searched in PubMed, Cochrane library, Synapse and 1000 Genomes databases following PRISMA guidelines for identifying relevant studies. Aggregated risk was estimated by RevMan software using either fixed/random-effects models where P values<0.05 (two-sided) were considered statistically significant. Nine studies comprising 16,132 ACS patients undergoing PCI were included in this analysis in which 2,746 and 2,640 patients were in the CYP2C19 LoF clopidogrel and alternatives treatment group, respectively. It was demonstrated that patients treated with prasugrel or ticagrelor significantly reduced the risk of MACEs (RR 0.58; 95% CI 0.45-0.76; P<0.0001) as compared to patients with clopidogrel where both groups carrying CYP2C19 LoF alleles. Subgroup analysis showed that prasugrel or ticagrelor significantly reduced the risk of cardiovascular death (RR 0.44; 95% CI: 0.25-0.74; P=0.002) and MI (RR 0.60; 95% CI: 0.44-0.81; P=0.0008) while other clinical outcomes were not found statistically significant between these two groups; stroke (RR 0.77; 95% CI: 0.43-1.38; P =0.39), stent thrombosis (RR 0.67; 95% CI: 0.38-1.18; P =0.17), unstable angina (RR 0.55; 95% CI: 0.13-2.33; P =0.42), revascularisation (RR 0.79; 95% CI: 0.28-2.24; P=0.66). Bleeding events were not found significantly different between these groups (RR 1.06; 95% CI: 0.88-1.28; P=0.55). Considering efficacy and safety, alternative antiplatelets (e.g. prasugrel or ticagrelor) may be regarded as better treatment option as compared to clopidogrel for ACS patients undergoing PCI.
1HNMR-Based Discriminatory Analysis of Eurycoma longifolia from Different Locations and Establishing a Profile for Primary Metabolites Identification and Quassinoids Quantification

Ebrahimi F, Ibrahim B, Teh CH, Murugaiyah V, Lam CK

Planta Med, 2017 Jan;83(1-02):172-182.
PMID: 27399233 DOI: 10.1055/s-0042-110857

Quassinoids, the major secondary metabolites of Eurycoma longifolia roots, improve male fertility. Hence, it is crucial to investigate their quantitative level in E. longifolia extracts. A profile was established to identify the primary metabolites and major quassinoids, and quantify quassinoids using external calibration curves. Furthermore, the metabolic discrimination of E. longifolia roots from different regions was investigated. The (1)H-NMR spectra of the quassinoids, eurycomanone, eurycomanol, 13,21-dihydroeurycomanone, and eurycomanol-2-O-β-D-glycopyranoside were obtained. The (1)H-NMR profiles of E. longifolia root aqueous extracts from Perak (n = 30) were obtained and used to identify primary metabolites and the quassinoids. Selangor, Kedah, Terengganu (n = 5 for each), and Perak samples were checked for metabolic discrimination. Hotelling's T(2) plot was used to check for outliers. Orthogonal partial least-squares discriminant analysis was run to reveal the discriminatory metabolites. Perak samples contained formic, succinic, methylsuccinic, fumaric, lactic, acetic and syringic acids as well as choline, alanine, phenylalanine, tyrosine, α-glucose, eurycomanone, eurycomanol, 13,21-dihydroeurycomanone, and eurycomanol-2-O-β-D-glycopyranoside. The extracts from other locations contained the same metabolites. The limit of quantification values were 1.96 (eurycomanone), 15.62 (eurycomanol), 3.91 (13,21-dihydroeurycomanone), and 31.25 (eurycomanol-2-O-β-D-glycopyranoside) ppm. The Hotelling's T(2) plot revealed no outlier. The orthogonal partial least-squares discriminant analysis model showed that choline, eurycomanol, eurycomanol-2-O-β-D-glycopyranoside, and lactic and succinic acid levels were different among regions. Terengganu and Perak samples contained higher amounts of eurycomanol and eurycomanol-2-O-β-D-glycopyranoside, respectively. The current approach efficiently detected E. longifolia root metabolites, quantified the quassinoids, and discriminated E. longifolia roots from different locations. These findings could be applicable to future research on E. longifolia where the higher content of quassinoids is required.
Effects of the CYP2C19 LoF allele on major adverse cardiovascular events associated with clopidogrel in acute coronary syndrome patients undergoing percutaneous coronary intervention: a meta-analysis

Biswas M, Sukasem C, Khatun Kali MS, Ibrahim B

Pharmacogenomics, 2022 02;23(3):207-220.
PMID: 35042400 DOI: 10.2217/pgs-2021-0098

The aggregated risk of major adverse cardiovascular events (MACE) in acute coronary syndrome (ACS) patients inheriting CYP2C19 loss-of function (LoF) alleles who underwent percutaneous coronary intervention (PCI) and were treated with clopidogrel is controversial. In the current study, we searched the literature in different databases for eligible studies. The risk ratio (RR) was measured where p<0.05 was statistically significant. The ACS patients with either one or two CYP2C19 LoF alleles who underwent PCI, treated with clopidogrel were correlated with a significantly escalated risk of MACE compared with noncarriers (RR: 1.53, 95% CI: 1.39-1.69, p < 0.00001), driven by CV death (RR: 1.88, 95% CI: 1.18-3.01, p = 0.008), MI (RR: 1.67, 95% CI: 1.21-2.31, p = 0.002) and ST (RR: 1.90, 95% CI: 1.27-2.84, p = 0.002). Patients with two CYP2C19 LoF alleles were correlated with significantly greater risk of MACE compared with noncarriers (RR: 3.91, 95% CI: 2.78-5.50, p < 0.00001). Further analysis revealed that the risk of MACE was markedly significant in Asian patients (RR: 2.02, 95% CI: 1.67-2.44, p < 0.00001) and was comparatively low significance in western patients (RR: 1.35, 95% CI: 1.20-1.52, p < 0.00001). There was no significantly different bleeding events in patients with CYP2C19 LoF alleles compared with noncarriers (RR: 0.99, 95% CI: 0.85-1.15, p = 0.87). The ACS patients inheriting CYP2C19 LoF alleles, who underwent PCI and were treated with clopidogrel were correlated with significantly increased risk of MACE compared with noncarriers.
Chronic obstructive pulmonary disease and emerging ER stress-related therapeutic targets

Yeap JW, Ali IAH, Ibrahim B, Tan ML

Pulm Pharmacol Ther, 2023 Aug;81:102218.
PMID: 37201652 DOI: 10.1016/j.pupt.2023.102218

COPD pathogenesis is frequently associated with endoplasmic reticulum stress (ER stress) progression. Targeting the major unfolded protein response (UPR) branches in the ER stress pathway may provide pharmacotherapeutic selection strategies for treating COPD and enable relief from its symptoms. In this study, we aimed to systematically review the potential role of the ER stress inhibitors of major UPR branches (IRE1, PERK, and ATF6) in COPD-related studies and determine the current stage of knowledge in this field. The systematic review was carried out adhering to the PRISMA checklist based on published studies obtained from specific keyword searches of three databases, namely PubMed, ScienceDirect and Springer Database. The search was limited to the year 2000-2022 which includes all in vitro studies, in vivo studies and clinical trials related to the application of ER stress inhibitors toward COPD-induced models and disease. The risk of bias was evaluated using the QUIN, SYRCLE, revised Cochrane risk of bias tool for randomized trials (RoB 2.0) and NIH tool respectively. A total of 7828 articles were screened from three databases and a final total of 37 studies were included in the review. The ER stress and UPR pathways are potentially useful to prevent COPD progression and attenuate the exacerbation of COPD and related symptoms. Interestingly, the off-target effects from inhibition of the UPR pathway may be desirable or undesirable depending on context and therapeutic applications. Targeting the UPR pathway could have complex consequences as the production of ER molecules involved in folding may be impaired which could continuously provoke misfolding of proteins. Although several emerging compounds were noted to be potentially useful for targeted therapy against COPD, clinical studies have yet to be thoroughly explored.
Addressing the standardisation of internal standards and preservative used in human bio fluids for NMR analysis: a method optimization

Abd Aziz F, Ibrahim B, Murugaiyah V, Sarriff A

Drug Metab Pers Ther, 2021 Mar 04.
PMID: 33662189 DOI: 10.1515/dmdi-2020-0154

OBJECTIVES: A database comprising multivariate data in developing a model from nuclear magnetic resonance (NMR) analysis using human bio fluids are necessary to have reproducibility and reliability of the data. To achieve reproducibility of the data, standardised experiments, including internal standard and preservative used should be attained, especially for samples such as human bio fluids to hinder the variation among samples. The aim of the study was to optimise in commonly used human bio fluids (serum and urine) for a suitable internal standard and preservative used in extended storage samples for NMR analysis.
METHODS: Serum and urine samples were collected from healthy human subjects. The experiment was divided into two parts, part one to evaluate 2,2,2,2-tetradeutero-4,4-dimethyl-4-silapentanoic acid (TSP) and 4,4-dimethyl-4-silapentane-1-ammonium trifluoroacetate (DSA) as the optimal internal standard for the serum and urine samples. The second part investigated the effects of preservatives in the serum and urine samples on extended storage.
RESULTS: Overall, TSP and DSA are suitable to be used as an internal standard in human urine samples. However, DSA is a superior internal standard in serum samples for NMR analysis. For the effect of preservative, the results indicated that human serum and urine samples could be stored without addition of preservative in -80 °C, as no changes in NMR fingerprinting have been observed during storage in the absence or presence of the preservative.
CONCLUSIONS: The findings suggest the use of DSA and TSP as an internal standard in serum and urine samples, respectively. Storage of serum and urine samples without any addition of preservative for an extended period has no effect on the metabolites changes. By having a standardised method, it will offer a considerable saving in both operator and spectrometer time and most importantly produce reproducible and reliable data.

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