Sameh Alzubiedi

Background. Globally, pharmacovigilance activities were affected by COVID-19. Therefore, several competent health authorities around the world, including several countries in the Middle East, have issued guidelines and practices to ensure that pharmacovigilance activities are maintained and continued during the pandemic. Objective. The aim of this study was to assess the impact of COVID-19, preparedness and performance of national pharmacovigilance systems in participating countries during COVID-19 pandemic. Methods. This was a cross- sectional study that was conducted between July and October 2020. National pharmacovigilance centres in 18 Arab countries in the Middle East were invited to participate in this study. Descriptive analysis was used to summarize and present the results of this study. Results. Responses were obtained from 14 (77.8%) Arab countries. Ten of participating countries (71.4%) have either specific national PV guidelines or local PV practices during the COVID-19 pandemic. Adverse events reporting was the main PV activity that was covered by PV guidelines and practices. National guidelines and practices covered other PV activities in 8 (57.14%) of the participating countries. Performance and practices of national PV centres vary considerably among participating countries during the pandemic. Conclusion. The findings highlight the differences in preparedness and performance of different national PV centres in participating Middle Eastern countries. Improving digital infrastructure among participating countries could serve as a useful tool to minimize the impact of the pandemic on PV activities.

(1) Background: Most patients with atrial fibrillation, on warfarin therapy, are at higher risk of morbidity and mortality. However, data targeting patients with atrial fibrillation, who take warfarin therapy, are limited in Jordan. This study aimed to provide in-depth analysis of a cohort of patients with atrial fibrillation on warfarin regarding patients’ characteristics, atrial fibrillation related symptoms, interventions, comorbidities, and 12-months outcomes. (2) Methods: The study enrolled 645 patients with atrial fibrillation, on warfarin, from 28 health settings across Jordan. Standardized clinical data form was utilized to collect data upon enrollment, at one, six, and 12 months post initial assessment. Descriptive statistics were used for the description of variables. (3) Results: The most commonly reported symptoms were palpitation (41.4%) shortness of breath (39.1%) and fatigue (26.2%). The prevalent comorbidities associated with atrial fibrillation were congestive heart failure (22.5%), valvular heart diseases (16.6%), and cerebral vascular accident (16.3%). The embolic (32.4%) and thrombotic cerebral vascular accident (16.2%) were the most common type. Major bleeding associated with hospitalization was the most frequent type of bleeding (10 out of 24). (4) Conclusions: Jordanians, using anticoagulation, need to be constantly monitored in terms of their characteristics, symptoms, and any potential complications, to ensure its optimal therapeutic dose and prevent any potential health complications.

Background: Warfarin, a commonly prescribed oral anticoagulant, relies on maintaining effective therapeutic levels as measured by the time within therapeutic range (TTR) and international normalized ratio (INR). However, the narrow therapeutic index of warfarin, influenced by both genetic and non-genetic factors, poses a significant risk of bleeding or coagulation complications. Identifying predictors of stable INR levels in warfarin-naïve patients is crucial to improve treatment safety and efficacy. Methods: This retrospective study conducted between 2018 and 2021 at Queen Alia Hospital Institute QAHI – RMS aimed to identify the impact of patient demographics, co-morbidities, and drug-drug interactions on stable, sub-therapeutic, and supra-therapeutic INR readings. Additionally, the study sought to determine risk factors for warfarin toxicity and major bleeding events associated with warfarin treatment. Results: Medical records of 163 warfarin-naïve patients (103 males, 60 females) with a baseline INR ≤1.2 were analyzed. Patients were admitted as emergency cases or transferred from internal medicine to the warfarin clinic. The majority of patients were under 65 years of age, overweight, and received warfarin for heart valve replacement or atrial fibrillation. Polypharmacy was common among the patients. Analysis revealed both good responders (24.5%) and poor responders (75.5%) in terms of TTR%. Conclusion: Predictors of warfarin anticoagulation may include age, gender, smoking status, and concomitant medication use. Considering these factors when managing warfarin therapy can improve treatment outcomes and patient safety.

Pharmacovigilance (PV) activities were affected by COVID-19. Therefore, several health authorities around the world have issued guidelines and practices to ensure that PV activities are maintained ...

Eltrombopag is a thrombopoietic growth factor that is approved for the treatment of thrombocytopenia in chronic hepatitis C virus (HCV) patients. We aimed to describe eltrombopag population pharmacokinetics in hepatitis C patients. Bayesian statistical approach will be applied to screen for patients’ characteristics associated with eltrombopag pharmacokinetic parameters.

In this study, we aim to identify patient characteristics that predict severe thrombocytopenia induced by peginterferon alfa-2a in hepatitis C virus–infected patients. Demographic, clinical, and genetic data collected from patients with chronic hepatitis C virus infection (n = 232; age ≥18 years) who received peginterferon alfa-2a following eltrombopag treatment. Predictors of severe thrombocytopenia (platelet count below 50 GI/L) were identified using a 2-step approach: First, univariate analysis, using χ2 test for categorical variables and t test for continuous variables, was performed to identify possible predictors of severe thrombocytopenia (P < 0.05). Second, a logistic regression with backward stepwise selection was then performed using predictors identified in univariate analysis step to produce final model containing independent predictors at P < 0.05. Logistic model identified several predictors of severe thrombocytopenia. Increased spleen length and increased alkaline phosphatase levels increases the likelihood of severe thrombocytopenia. However, being Central/South Asian, increased neutrophils count and increased platelet baseline count decreases the probability of developing severe thrombocytopenia. In summary, we identified several patient characteristics that predict severe thrombocytopenia induced by peginterferon alfa-2a. Early selection of individuals with high risk of developing interferon-associated severe thrombocytopenia allows early intervention (such as eltrombopag treatment). Early intervention in turn minimizes the odds of developing severe thrombocytopenia and allows the continual of antiviral therapy before patient progress into liver decompensation.

Our objective was to explore artificial neural networks (ANNs) as a possible tool for dosage individualization of warfarin. Demographic, clinical, and genetic data were gathered from a previously collected cohort of patients with a stable warfarin dosage who were able to achieve an observed international normalized ratio of 2–3. Data from a cohort of 3,415 patients were used to develop an ANN dosing algorithm. Data from another cohort of 856 were used to validate the algorithm. The clinical significance of the ANN dosing algorithm was evaluated by calculating the percentage of patients whose predicted dosage of warfarin was within 20 % of the actual stable therapeutic dose. The clinical significance was also compared with a previously published dosing algorithm. A feed-forward neural network with three layers was able to successfully predict the ideal warfarin dosage in 48 % of the patients. The neural network model explained 48 % and 43 % of the dosage variability observed among patients in the derivation and validation cohorts, respectively. ANN analysis identified several predictors of warfarin dosage including race; age; height; weight; cytochrome P450 (CYP)2C9 genotype; VKORC1 genotype; sulfonamide, azole antifungals, or macrolide administration; carbamazepine, phenytoin, or rifampicin administration; and amiodarone administration. An ANN was applied to develop a warfarin dosing algorithm. The proposed dosing algorithm has the potential to recommend warfarin dosages that are close to the appropriate dosages.

Glucuronidation is one of the most important phase II metabolic pathways. It is catalyzed by a family of UDP-glucuronosyltransferase enzymes (UGTs). One of the subfamilies is UGT1A. Allele frequencies in UGT1A4 differ among ethnic groups. The aim of this study was to determine the allelic frequency of two most common defective alleles: UGT1A4*2 and UGT1A4*3 in a Jordanian population. A total of 216 healthy Jordanian Volunteers (165 males and 51 females) were included in this study. Genotyping for UGT1A4*1, UGT1A4*2 and UGT1A4*3 was done using a well established polymerase chain reaction–restriction fragment length polymorphism test. Among 216 random individuals studied for UGT1A4*2 mutation there were 26 individuals who were heterozygous, giving a prevalence of 12% and an allele frequency of 6.5%. Only one individual was homozygous for UGT1A4*2. The UGT1A4*3 mutation was detected as heterozygous in 9 of 216 individuals indicating a prevalence of 4.2% and allele frequency of 3.5%. Three individuals were homozygous for the UGT1A4*3 indicating a prevalence of 1.4%. The prevalence of UGT1A4*2 is similar to the Caucasians but different from other populations whilst the UGT1A4*3 prevalence in the Jordanian population is distinct from other populations. Our results provide useful information for the Jordanian population and for future genotyping of Arab populations in general.