The Impact of CYP2C19 Genotype on the Platelet Reactivity Index (PRI) among Chronic Coronary Syndromes (CCS) Patients Undergoing Percutaneous Coronary Intervention (PCI): Affectability of Rapid Genetic Testing.

BACKGROUND: In the Asian population, the presence of the CYP2C19 loss-of-function (LOF) allele is a known genetic variation. This allele is associated with a reduced capacity to metabolize clopidogrel into its active forms through the CYP2C19 enzyme, resulting in diminished platelet inhibition and an elevated risk of recurrent cardiovascular events. Regulatory authorities have recommended an alternative P2Y12 inhibitor, ticagrelor, for individuals carrying the LOF allele. Consequently, this study seeks to assess the impact of the CYP2C19 genotype on the Platelet reactivity index (PRI) using a rapid genetic testing approach in Asian patients with chronic coronary syndromes (CCS) who undergo percutaneous coronary intervention (PCI). METHODS: This prospective study employed a parallel design, single-center design, and randomized approach. Genotyping for the CYP2C19*2 and *3 polymorphisms was conducted using the Nested Allele-Specific Multiplex PCR (NASM-PCR) technique. Patients meeting the inclusion criteria underwent genotyping for CYP2C19 polymorphisms. Following PCI, patients were randomly assigned to receive either ticagrelor or clopidogrel. PRI assessments were performed four hours after loading dose administration. The trial was registered with ClinicalTrials.gov under the identifier NCT05516784. RESULTS: Among the 94 patients recruited for the study, 40 (42.55%) were identified as carriers of the LOF allele for CYP2C19*2 and *3 (*1/*2, *2/*2, *1/*3). Out of the 84 patients evaluated for PRI (44 receiving clopidogrel and 40 receiving ticagrelor), 21 (47.7%) of the clopidogrel group and 39 (97.5%) of the ticagrelor group exhibited a favorable response to antiplatelet therapy (PRI < 50). Patients treated with ticagrelor demonstrated superior antiplatelet responses compared to those receiving clopidogrel, regardless of LOF carrier status (P = 0.005 and < 0.001 for non-LOF and LOF carriers, respectively). CONCLUSION: NASM-PCR as a rapid genetic test holds promise for personalizing antiplatelet therapy in Asian CCS patients.

Chronic obstructive pulmonary disease and emerging ER stress-related therapeutic targets.

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.

Can patients achieve sufficient peak inspiratory flow rate (PIFR) with Turbuhaler® during acute exacerbation of asthma?

INTRODUCTION: Anti-inflammatory reliever (AIR) with or without regular maintenance delivered through Turbuhaler® has been widely recommended in the GINA strategy document. These patients are not prescribed with additional reliever inhalers, but dependent on Turbuhaler® during acute asthma episodes. The peak inspiratory flow rate (PIFR) is crucial in drug delivery from a dry powder inhaler (DPI) such as Turbuhaler®. Despite its increasing usage, there are some concerns that patients on Turbuhaler® are not able to achieve adequate PIFR during acute exacerbation of asthma. OBJECTIVE: This study aimed to assess the PIFR at resistance settings that matched Turbuhaler® in patients with acute exacerbation of asthma. METHODOLOGY: A six-month cross-sectional study was conducted at the Emergency Department (ED) of Hospital Sultanah Bahiyah and Hospital Kulim, Kedah, Malaysia. Adult patients diagnosed with mild to moderate acute exacerbations of asthma were recruited. The PIFRs were measured using the In-Check DIAL G16 that was set to simulate the resistance of Turbuhaler® (R3). The PIFRs were assessed before (pre) and after (post) the initial bronchodilator (BD) treatment at the ED. The minimal required PIFR was defined as flow rates ≥ 30 L/min while a PIFR of 60 L/min was considered as optimal. RESULTS: A total of 151 patients (81 females and 70 males) were recruited. The mean age was 37.5 years old with a range between 18 and 79 years old. The results showed that 98% (n = 148) of patients managed to achieve the minimal PIFR required for pre-BD. The mean PIFR pre-BD was 60 ± 18.5 L/min and post-BD was 70 ± 18.5 L/min. Furthermore, more than half (54%, n = 82) of the patients recorded PIFR ≥ 60 L/min during pre-BD, and about three-quarters (71%, n = 92) achieved PIFR ≥ 60 L/min post-BD. The PIFR showed a moderate correlation with peak expiratory flow rate (PEFR) (r = 0.55, 95% CI: 0.43-0.65, p < 0.001). CONCLUSION: The majority of patients with asthma in the present study were able to achieve sufficient PIFR from Turbuhaler® during mild to moderate acute exacerbations.

Mesenchymal stem cell-derived extracellular vesicles for metabolic syndrome therapy: Assessing efficacy with nuclear magnetic resonance spectroscopy.

Metabolic syndrome (MetS) represents a cluster of metabolic abnormalities. The prevalence of MetS has surged, transforming it into a pressing public health concern that could potentially affect around 20%-25% of the global population. As MetS continues its ascent, diverse interventions, pharmacological, nonpharmacological and combined have been deployed. Yet, a comprehensive remedy that fully eradicates MetS symptoms remains elusive, compounded by the risks of polypharmacy's emergence. Acknowledging the imperative to grasp MetS's intricate pathologies, deeper insights for future research and therapy optimisation become paramount. Conventional treatments often target specific syndrome elements. However, a novel approach emerges in mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) therapy, promising a holistic shift. MSC-EVs, tiny membranous vesicles secreted by mesenchymal stem cells, have garnered immense attention for their multifaceted bioactivity and regenerative potential. Their ability to modulate inflammation, enhance tissue repair and regulate metabolic pathways has prompted researchers to explore their therapeutic application in MetS. This review primarily aims to provide an overview of how MSC-EVs therapy can improve metabolic parameters in subjects with MetS disease and also introduce the usefulness of NMR spectroscopy in assessing the efficacy of MSC-EVs therapy for treating MetS.

Prediction of Low-Dose Aspirin-Induced Gastric Toxicity Using Nuclear Magnetic Resonance Spectroscopy-Based Pharmacometabolomics in Rats.

BACKGROUND: Low-dose aspirin (LDA) is the backbone for secondary prevention of coronary artery disease, although limited by gastric toxicity. This study aimed to identify novel metabolites that could predict LDA-induced gastric toxicity using pharmacometabolomics. METHODS: Pre-dosed urine samples were collected from male Sprague-Dawley rats. The rats were treated with either LDA (10 mg/kg) or 1% methylcellulose (10 mL/kg) per oral for 28 days. The rats' stomachs were examined for gastric toxicity using a stereomicroscope. The urine samples were analyzed using a proton nuclear magnetic resonance spectroscopy. Metabolites were systematically identified by exploring established databases and multivariate analyses to determine the spectral pattern of metabolites related to LDA-induced gastric toxicity. RESULTS: Treatment with LDA resulted in gastric toxicity in 20/32 rats (62.5%). The orthogonal projections to latent structures discriminant analysis (OPLS-DA) model displayed a goodness-of-fit (R2Y) value of 0.947, suggesting near-perfect reproducibility and a goodness-of-prediction (Q2Y) of -0.185 with perfect sensitivity, specificity and accuracy (100%). Furthermore, the area under the receiver operating characteristic (AUROC) displayed was 1. The final OPLS-DA model had an R2Y value of 0.726 and Q2Y of 0.142 with sensitivity (100%), specificity (95.0%) and accuracy (96.9%). Citrate, hippurate, methylamine, trimethylamine N-oxide and alpha-keto-glutarate were identified as the possible metabolites implicated in the LDA-induced gastric toxicity. CONCLUSION: The study identified metabolic signatures that correlated with the development of a low-dose Aspirin-induced gastric toxicity in rats. This pharmacometabolomic approach could further be validated to predict LDA-induced gastric toxicity in patients with coronary artery disease.

Screening and Determination of Synthetic PDE-5 Inhibitors in Adulterated Sexual Enhancement Supplements.

This paper reports an important investigation and quantification of adulteration of sexual enhancement supplements with prescription medicines available in United Arab Emirates (UAE): tadalafil, sildenafil and vardenafil. A total of 158 sexual enhancement supplements were collected and analyzed in the current study. The samples were screened using REVERSE-phase liquid chromatography tandem high-resolution mass spectrometry/mass spectrometry (RP-HPLC-MS/MS). Of all sexual enhancements, 12.7% (95% CI: 7.4-18) contained undeclared sildenafil, 3.8% (95% CI: 0.78-6.81) contained undeclared tadalafil and 1.9% (95% CI: 0.25-4.05) contained undeclared vardenafil. Of all sexual enhancement supplements, 13.9% (95% CI: 8.5-19.4) contained significant concentrations of sildenafil, tadalafil or vardenafil. While the study found relatively low levels of undeclared pharmaceutical ingredients in the sexual enhancement dietary supplements available on the UAE market, it is likely that patients with ED tend to consume multiple such supplements daily, thereby exposing themselves to highly elevated cumulative levels.

The impact of SARS-CoV-2 treatment on the cardiovascular system: an updated review.

The coronavirus disease-2019 (COVID-19) pandemic has become a major global health problem. COVID-19 is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and exhibits pulmonary and extrapulmonary effects, including cardiovascular involvement. There are several attempts to identify drugs that could treat COVID-19. Moreover, many patients infected with COVID-19 have underlying diseases, particularly cardiovascular diseases. These patients are more likely to develop severe illnesses and would require optimized treatment strategies. The current study gathered information from various databases, including relevant studies, reviews, trials, or meta-analyses until April 2022 to identify the impact of SARS-CoV-2 treatment on the cardiovascular system. Studies have shown that the prognosis of patients with underlying cardiovascular disease is worsened by COVID-19, with some COVID-19 medications interfering with the cardiovascular system. The COVID-19 treatment strategy should consider many factors and parameters to avoid medication-induced cardiac injury, mainly in elderly patients. Therefore, this article provides a synthesis of evidence on the impact of different COVID-19 medications on the cardiovascular system and related disease conditions.

Adequacy of Empiric Antibiotics Therapy and Its Impact on Outcomes in Adult Critically Ill Sepsis Patients: A Review.

Sepsis is a medical emergency that involves a systemic immunological response due to an infection, resulting in the end-stage-organs malfunction and death. It is associated with high mortality rate despite a better understanding of the disease pathology and the mechanism involved. This review was designed to summarise the available evidences regarding the adequacy of the empiric antimicrobial therapy (EAMT), its predictors and its impact on the outcomes in intensive care unit (ICU) sepsis patients. Providing an adequate EAMT is considered one of the cornerstones of sepsis management as it has been found to be associated with better survival and is a good predictor for shorter ICU-length-of-stay. In contrast, inadequate EAMT in sepsis patients is associated with poor clinical outcomes including increased mortality and prolonged hospital stay. Evidence from this review suggest that it is important to identify determinants of inadequate EAMT to optimise the antimicrobial therapy provided to sepsis patients. Predictors of inadequate EAMT included co-morbidities (cancer), source and type of infection, higher Acute Physiology and Chronic Health Evaluation (APACHI-II) score and long hospital stay prior to the infection. As EAMT is considered as one of the effective treatment strategies to prevent sepsis associated death, healthcare providers should ensure the adequate antimicrobial therapy is provided for sepsis patients to improve and optimise their management.

Translation and validation of the Test of Adherence to Inhalers (TAI) questionnaire among adult patients with asthma in Malaysia.

OBJECTIVE: The Test of Adherence to Inhalers (TAI) is a validated self-reported questionnaire that can reliably assess adherence to inhalers through patient self-report. However, it was not available in Bahasa Melayu (BM) language, nor has it been validated for use in the Malaysian population. The study aimed, therefore, to translate the 10-item TAI questionnaire into BM and evaluate its psychometric properties. METHODS: The translation of the English version of the valid 10-item TAI questionnaire into BM was followed by subjecting it to a series of tests establishing factorial, concurrent and known group validities. Concurrent validity was assessed through Spearman's rank correlation coefficient against pharmacy refill-based adherence scores. Known group validity was assessed by cross-tabulation against asthma symptom control and using chi-square test. The internal consistency of the test scale was determined by a test-retest method using Cronbach's alpha (α) value and intraclass correlation coefficients. RESULTS: A total of 120 adult asthma patients participated in the study. A 2-factor structure was obtained and confirmed with acceptable fit indices; CFI, NFI, IFI, TLI >0.9 and, RMSEA was 0.08. The reliability of the scale was 0.871. The test-retest reliability coefficient for the total sum score was 0.832 (p < 0.01), which indicated good reliability. The 10-item TAI-BM established concurrent and known group validities. The sensitivity and specificity of the tool were >85%. CONCLUSIONS: The scale successfully translated into BM and validated. The 10-item TAI-BM appears fit for use in testing inhaler adherence of Malaysian patients with asthma.

The effects of high-fat diet and metformin on urinary metabolites in diabetes and prediabetes rat models.

High-fat diet (HFD) interferes with the dietary plan of patients with type 2 diabetes mellitus (T2DM). However, many diabetes patients consume food with higher fat content for a better taste bud experience. In this study, we examined the effect of HFD on rats at the early onset of diabetes and prediabetes by supplementing their feed with palm olein oil to provide a fat content representing 39% of total calorie intake. Urinary profile generated from liquid chromatography-mass spectrometry analysis was used to construct the orthogonal partial least squares discriminant analysis (OPLS-DA) score plots. The data provide insights into the physiological state of an organism. Healthy rats fed with normal chow (NC) and HFD cannot be distinguished by their urinary metabolite profiles, whereas diabetic and prediabetic rats showed a clear separation in OPLS-DA profile between the two diets, indicating a change in their physiological state. Metformin treatment altered the metabolomics profiles of diabetic rats and lowered their blood sugar levels. For prediabetic rats, metformin treatment on both NC- and HFD-fed rats not only reduced their blood sugar levels to normal but also altered the urinary metabolite profile to be more like healthy rats. The use of metformin is therefore beneficial at the prediabetes stage.

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.

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.

The Role of Genetic Polymorphism and Other Factors on Clopidogrel Resistance (CR) in an Asian Population with Coronary Heart Disease (CHD).

Clopidogrel is a widely-used antiplatelet drug. It is important for the treatment and prevention of coronary heart disease. Clopidogrel can effectively reduce platelet activity and therefore reduce stent thrombosis. However, some patients still have ischemic events despite taking the clopidogrel due to the alteration in clopidogrel metabolism attributable to various genetic and non-genetic factors. This review aims to summarise the mechanisms and causes of clopidogrel resistance (CR) and potential strategies to overcome it. This review summarised the possible effects of genetic polymorphism on CR among the Asian population, especially CYP2C19 *2 / *3 / *17, where the prevalence rate among Asians was 23.00%, 4.61%, 15.18%, respectively. The review also studied the effects of other factors and appropriate strategies used to overcome CR. Generally, CR among the Asian population was estimated at 17.2-81.6%. Therefore, our overview provides valuable insight into the causes of RC. In conclusion, understanding the prevalence of drug metabolism-related genetic polymorphism, especially CYP2C19 alleles, will enhance clinical understanding of racial differences in drug reactions, contributing to the development of personalised medicine in Asia.

Association of Sex, Age, and Comorbidities with Mortality in COVID-19 Patients: A Systematic Review and Meta-Analysis.

INTRODUCTION: Although severe acute respiratory syndrome coronavirus-2 infection is causing mortality in considerable proportion of coronavirus disease-2019 (COVID-19) patients, however, evidence for the association of sex, age, and comorbidities on the risk of mortality is not well-aggregated yet. It was aimed to assess the association of sex, age, and comorbidities with mortality in COVID-2019 patients. METHODS: Literatures were searched using different keywords in various databases. Relative risks (RRs) were calculated by RevMan software where statistical significance was set as p < 0.05. RESULTS: COVID-19 male patients were associated with significantly increased risk of mortality compared to females (RR 1.86: 95% confidence interval [CI] 1.67-2.07; p < 0.00001). Patients with age ≥50 years were associated with 15.4-folds significantly increased risk of mortality compared to patients with age <50 years (RR 15.44: 95% CI 13.02-18.31; p < 0.00001). Comorbidities were also associated with significantly increased risk of mortality; kidney disease (RR 4.90: 95% CI 3.04-7.88; p < 0.00001), cereborovascular disease (RR 4.78; 95% CI 3.39-6.76; p < 0.00001), cardiovascular disease (RR 3.05: 95% CI 2.20-4.25; p < 0.00001), respiratory disease (RR 2.74: 95% CI 2.04-3.67; p < 0.00001), diabetes (RR 1.97: 95% CI 1.48-2.64; p < 0.00001), hypertension (RR 1.95: 95% CI 1.58-2.40; p < 0.00001), and cancer (RR 1.89; 95% CI 1.25-2.84; p = 0.002) but not liver disease (RR 1.64: 95% CI 0.82-3.28; p= 0.16). CONCLUSION: Implementation of adequate protection and interventions for COVID-19 patients in general and in particular male patients with age ≥50 years having comorbidities may significantly reduce risk of mortality associated with COVID-19.

It is time to change the way we manage mild asthma: an update in GINA 2019.

Asthma is a heterogeneous lung disease, usually characterised by chronic airway inflammation. Although evidence-based treatments are available in most countries, asthma control remains suboptimal, and asthma-related deaths continue to be an ongoing concern. Generally, it is believed that between 50 to 75% of patients with asthma can be considered as having mild asthma.Previous versions of Global Initiative for Asthma (GINA) suggested that mild asthma in adults can be well managed with either reliever medications, for example, short-acting beta2 agonists (SABA) alone or with the additional use of controllers such as regular low-dose inhaled corticosteroids (ICS). Given the low frequency or non-bothersome nature of symptoms in mild asthma, patients' adherence towards their controller medications, especially to ICS is usually not satisfactory. Such patients often rely on SABA alone to relieve symptoms, which may contribute to SABA over-reliance. Overuse of relievers such as SABAs has been associated with poor asthma outcomes, such as exacerbations and even deaths. The new GINA 2019 asthma treatment recommendations represent significant shifts in asthma management at Steps 1 and 2 of the 5 treatment steps. The report acknowledges an emerging body of evidence suggesting the non-safety of SABAs overuse in the absence of concomitant controller medications, therefore does not support SABA-only therapy in mild asthma and has included new off-label recommendations such as symptom-driven (as-needed) low dose ICS-formoterol and "low dose ICS taken whenever SABA is taken".The GINA 2019 report highlights significant updates in mild asthma management and these recommendations represent a clear deviation from decades of clinical practice mandating the use of symptom-driven SABA treatment alone in those with mild asthma. While the new inclusions of strategies such as symptom-driven (as-needed) ICS-formoterol and "ICS taken whenever SABA is taken" are based on several key trials, data in this context are still only emergent data, with clear superiority of as needed ICS-formoterol combinations over maintenance ICS regimens yet to be established for valid endpoints. Nevertheless, current and emerging data position the clinical asthma realm at a watershed moment with imminent changes for the way we manage mild asthma likely in going forward.

Evaluation of risk factors associated with drug-resistant tuberculosis in Yemen: data from centres with high drug resistance.

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.

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

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 < 47 reflects impairment of functions, whereas a mental component summary (MCS) score of < 43 indicates a risk of depression. RESULT: At the beginning of treatment, the mean scores for all health domains were < 47 NBS points (PF = 40.7, RP = 16.1, BP = 21.6, GH = 28.3, VT = 14.55, SF = 25.9, RE = 13.7, and MH = 14.7). At the completion of treatment, all eight health domains increase compare to beginning of treatment (PF = 59.3, RP = 31.1, BP = 40.9, GH = 48.5, VT = 30.5, SF = 46.6, RE =26.6 & MH = 27.7), but a follow-up duration of 1 year after completing treatment showed decreased NBS points in all domains (PF = 51.5, RP = 30.6, BP = 39.1, GH = 47.8, VT = 30.2, SF = 43.7, RE =26.4 & MH = 27.2). Age, history of streptomycin use, baseline lung cavity, marital status and length of sickness before MDR-TB diagnosis were predictive of in PCS score differences, whereas, age, smoking, baseline lung cavity, stigma, residence, marital status and length of sickness before MDR-TB diagnosis were predictive of MCS scores differences. CONCLUSION: The length of sickness before DR-TB diagnosis was found to be predictive of the trends in both PCS and MCS scores. Despite the positive outcome of MDR-TB treatment, the low HRQoL scores obtained for all heath domains and especially for mental health reflect a high depression status of patients even after 1 year of completing therapy. Moreover, the poor HRQoL, particularly regarding mental health, of study participants at the end of treatment demands the need for urgent attention from national tuberculosis control programme managers. Therefore, the Yemen Ministry of Health and the National Tuberculosis Control Programme should implement an intervention programme to enhance HRQoL at the end of treatment to avoid any further negative consequences of MDRTB in patients after treatment. Moreover, The HRQoL data of patients with MDR-TB must be collected at the different stages of MDR-TB treatment to provide an additional parameter for assessing the effectiveness of the treatment programme. TRIAL REGISTRATION: SNOYEM 1452. Registered 01 February 2013.

Variation of δ2H, δ18O & δ13C in crude palm oil from different regions in Malaysia: Potential of stable isotope signatures as a key traceability parameter.

A total of 33 crude palm oil samples were randomly collected from different regions in Malaysia. Stable carbon isotopic composition (δ13C) was determined using Flash 2000 elemental analyzer while hydrogen and oxygen isotopic compositions (δ2H and δ18O) were analyzed by Thermo Finnigan TC/EA, wherein both instruments were coupled to an isotope ratio mass spectrometer. The bulk δ2H, δ18O and δ13C of the samples were analyzed by Hierarchical Cluster Analysis (HCA), Principal Component Analysis (PCA) and Orthogonal Partial Least Square-Discriminant Analysis (OPLS-DA). Unsupervised HCA and PCA methods have demonstrated that crude palm oil samples were grouped into clusters according to respective state. A predictive model was constructed by supervised OPLS-DA with good predictive power of 52.60%. Robustness of the predictive model was validated with overall accuracy of 71.43%. Blind test samples were correctly assigned to their respective cluster except for samples from southern region. δ18O was proposed as the promising discriminatory marker for discerning crude palm oil samples obtained from different regions. Stable isotopes profile was proven to be useful for origin traceability of crude palm oil samples at a narrower geographical area, i.e. based on regions in Malaysia. Predictive power and accuracy of the predictive model was expected to improve with the increase in sample size. Conclusively, the results in this study has fulfilled the main objective of this work where the simple approach of combining stable isotope analysis with chemometrics can be used to discriminate crude palm oil samples obtained from different regions in Malaysia. Overall, this study shows the feasibility of this approach to be used as a traceability assessment of crude palm oils.

1HNMR-Based Discriminatory Analysis of Eurycoma longifolia from Different Locations and Establishing a Profile for Primary Metabolites Identification and Quassinoids Quantification.

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 1H-NMR spectra of the quassinoids, eurycomanone, eurycomanol, 13,21-dihydroeurycomanone, and eurycomanol-2-O-ß-D-glycopyranoside were obtained. The 1H-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 T2 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-ß-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-ß-D-glycopyranoside) ppm. The Hotelling's T2 plot revealed no outlier. The orthogonal partial least-squares discriminant analysis model showed that choline, eurycomanol, eurycomanol-2-O-ß-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-ß-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.

The effectiveness of the McIsaac clinical decision rule in the management of sore throat: an evaluation from a pediatrics ward.

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.

Predictors of chronic kidney disease survival in type 2 diabetes: a 12-year retrospective cohort study utilizing estimated glomerular filtration rate.

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 < 0.001), and the use of beta-blockers (HR 139, 95% CI 112-173, p = 0.003). Implementing preventative measures, initiating early interventions, and developing personalized care plans tailored to address specific risk factors are imperative for reducing the impact of CKD. Additionally, the unforeseen findings related to eGFR highlight the ongoing need for research to deepen our understanding of the complexities of kidney disease.