wael h khreisat
@royalmedicalservices.com
pediatric neurology
Royal Medical Services
RESEARCH INTERESTS
neurology
Scopus Publications
Scopus Publications
Hamza A. Alsayouf, Osama Alsarhan, Wael Khreisat, and Azhar Daoud
MDPI AG
Atomoxetine is indicated for the management of attention deficit/hyperactivity disorder (ADHD) in children and adolescents aged 6 to 18 years. Few studies have assessed the safety and tolerability of atomoxetine in younger patients. This retrospective cohort study included 133 children aged 3–6 years who were diagnosed with ADHD comorbid with autism spectrum disorder (ASD). The primary endpoint was the evaluation of the safety profile of atomoxetine. In total, 50 patients (37.6%) experienced adverse events (AEs), which led to treatment discontinuation in 23 patients (17.3%). The most common AEs were gastrointestinal (24.1%), aggression or hostility (12.8%), and increased hyperactivity (9.0%). In the 23 patients who discontinued treatment, all the AEs resolved after treatment ceased. Among the 110 patients who completed at least 6 months’ treatment, atomoxetine titrated to a dose of 1.2–1.8 mg/kg/day appeared to be well tolerated and effective. The Clinical Global Impression—Improvement score improved to 1 (“very much improved”) and 2 (“much improved”) in 62.4% and 20.3% of children, respectively, at their last visit. Overall, atomoxetine appeared to be well tolerated in younger children with comorbid ADHD and ASD. Nevertheless, close patient monitoring remains essential, and the study limitations necessitate caution in generalizing these findings to broader populations. Long-term prospective studies are required.
Suha Jarad, Amal Akour, Wael H. Khreisat, Afrah K. Elshammari, and Saba Madae’en
SAGE Publications
Background: Rate of nonadherence to antiepileptic drugs (AEDs) in children is about 33%. Engaging clinical pharmacists in the management of patients has proved to increase adherence to medications which will improve the outcomes of treatment. Objectives: To investigate the effect of a clinical pharmacist-led education on the adherence to AEDs in pediatric patients with epilepsy. Secondary outcomes include effectiveness and safety of AEDs, satisfaction with information about AEDs provided to the caregivers, and patients quality of life (QoL). Methods: This was an interventional study where pediatric patients were randomly assigned to the intervention (n = 41) or the control (n = 40) group. A 30-minute clinical pharmacist-led educational interview to the parent/caregiver was provided to the first group as add-on to standard medical care received by latter. Outcomes were measured at baseline and after 8-week follow-up. Results: The intervention group had an increase in mean adherence score from 6 ± 1.09 at baseline to 7.6 ± 0.9 at follow-up ( P value < 0.001), while the control group had no significant change ( P value > 0.05), the difference between the 2 groups at follow-up was significant ( P value < 0.0001). No significant difference was observed between groups at follow-up with regard to effectiveness ( P value > 0.05), and safety ( P value = 0.08). While higher satisfaction with information ( P value < 0.0001), and higher QoL ( P value < 0.05) was observed in the intervention group. Conclusion and relevance: Clinical pharmacist-led education had a positive outcome on pediatric patients with epilepsy with regard to adherence, effectiveness, safety, satisfaction with information about AEDs, and QoL.
Laith N AL-Eitan, Islam M Al-Dalala, Afrah K Elshammari, Wael H Khreisat, Aseel F Nimri, Adan H Alnaamneh, Hanan A Aljamal, and Mansour A Alghamdi
Informa UK Limited
Purpose The aim of this study was to investigate the possible effects of single-nucleotide polymorphisms (SNPs) within SLC1A1, SLC6A1, FAM131B, GPLD1, F2, GABRG2, GABRA1, and CACNG5 genes on response to anti-epileptic drugs (AEDs) and the genetic predisposition of epilepsy in Jordanian patients. Patients and Methods A total of 299 healthy individuals and 296 pediatric patients from the Jordanian population were recruited. Blood samples are collected, and genotyping was performed using a custom platform array analysis. Results The SLC1A1 rs10815018 and FAM131B rs4236482 polymorphisms found to be associated with epilepsy susceptibility. Moreover, SLC1A1 rs10815018 and GPLD1 rs1126617 polymorphisms were associated with generalized epilepsy (GE), while FAM131B rs4236482 is associated with the focal phenotype. Regarding the therapeutic response, the genetic polymorphisms of FAM131B rs4236482, GABRA1 rs2279020, and CACNG5 rs740805 are conferred poor response (resistance) to AEDs. There was no linkage of GLPD1 haplotypes to epilepsy, its subtypes, and treatment responsiveness. Conclusion Our findings suggested that SLC1A1, FAM131B, and GPLD1 polymorphisms increasing the risk of generating epilepsy, while FAM131B, GABRA1, and CACNG5 variants may play a role in predicting drug response in patients with epilepsy (PWE).
Laith N AL-Eitan, Islam M. Al-Dalalah, Mohamed M. Mustafa, Mansour A. Alghamdi, Afrah K. Elshammari, Wael H. Khreisat, Mohammed N. Al-Quasmi, and Hanan A. Aljamal
Informa UK Limited
Background A total of 50 million persons were diagnosed worldwide with epilepsy. One-third of them are experiencing debilitating seizures despite optimum anti‐epileptic drugs (AEDs) treatment. Several studies have suggested that CYP3A5, CHRM2, and ZNF498 influence the pharmacokinetics of AEDs. Therefore, the severity of the disease as well as the degree of response to the AEDs could be affected by the genetic polymorphisms within these genes. Objectives In this study, we assessed the effect of certain single nucleotide polymorphisms (SNPs) within CYP3A5, CHRM2, and ZNF498 genes on the susceptibility to develop epilepsy and the responsiveness to AEDs treatment. Methods A case–control and pharmacogenetic study was conducted on samples of 299 healthy individuals in addition to 296 epileptic patients. Genotypic, allelic, and clinical data association were performed for the selected polymorphisms within the (rs324649, rs420817, rs15524, and rs1859690) in the Jordanian population. Results The analysis revealed no significant association of the investigated SNPs with epilepsy in general, partial and generalized epilepsy as well as drug responsiveness. CYP3A5 and ZNF498 were associated with family history (P=0.003 and P=0.002, respectively) and the classification of epilepsy for the ZNF498 variant (P=0.009). On the other hand, CHRM2 was not linked to either disease severity or treatment responsiveness. Conclusion Our results failed to confirm the association of CYP3A5, ZNF498, and CHRM2 variants with either disease development or treatment response. Clinical pharmacogenetic studies may contribute to treatment personalization, appropriate drug dose selection, minimizing drug adverse reactions, increasing drug efficacy, and reducing the costive burdens.
Laith N AL-Eitan, Islam M Al-Dalalah, Mohamed M Mustafa, Mansour A Alghamdi, Afrah K Elshammari, Wael H Khreisat, and Hanan A Aljamal
Informa UK Limited
Background Epilepsy is one of the most common neurological diseases with unclear etiology where its genetic background and treatment regime still need further exploration. Objectives This study designed to evaluate the pharmacogenomics of MTHFR and ABCC2 genes, and their association with epilepsy susceptibility among Jordanian population. Methods A case-control study was conducted on Jordanian cohort of 296 epileptic patients and 299 healthy individuals. Custom platform array was used to genotype the genetic polymorphisms within MTHFR (rs1801133) and ABCC2 (rs717620, rs3740066, rs2273697) genes. Results This study revealed a significant genetic association of MTHFR rs1801133 polymorphism with susceptibility to generalized in general and generalized tonic-clonic epilepsy (GTCE)(p=0.018 and 0.01, respectively). Regarding ABCC2 gene, rs717620 was of linkage with generalized and GTCE subtypes (p=0.045 and 0.048, respectively), while rs717620 was associated with poor responder patients (p=0.036) with no linkage of the ABCC2 haplotypes. Conclusions MTHFR and ABCC2 polymorphisms showed an association with either epilepsy types in general or subtypes and treatment response among Jordanian population. This study also suggested that these gene polymorphisms have an important role in epilepsy development and drug effectiveness and could be of a great impact in the era of epilepsy diagnosis and treatment.
Laith AL-Eitan, Islam Al-Dalalah, Afrah Elshammari, Wael Khreisat, and Ayah Almasri
MDPI AG
This study aims to investigate the effects of the three potassium channel genes KCNA1, KCNA2, and KCNV2 on increased susceptibility to epilepsy as well as on responsiveness to antiepileptic drugs (AEDs). The pharmacogenetic and case-control cohort (n = 595) consisted of 296 epileptic patients and 299 healthy individuals. Epileptic patients were recruited from the Pediatric Neurology clinic at the Queen Rania Al Abdullah Hospital (QRAH) in Amman, Jordan. A custom platform array search for genetic association in Jordanian-Arab epileptic patients was undertaken. The MassARRAY system (iPLEX GOLD) was used to genotype seven single nucleotide polymorphisms (SNPs) within three candidate genes (KCNA1, KCNA2, and KCNV2). Only one SNP in KCNA2, rs3887820, showed significant association with increased risk of susceptibility to generalized myoclonic seizure (p-value < 0.001). Notably, the rs112561866 polymorphism of the KCNA1 gene was non-polymorphic, but no significant association was found between the KCNA1 (rs2227910, rs112561866, and rs7974459) and KCNV2 (rs7029012, rs10967705, and rs10967728) polymorphisms and disease susceptibility or drug responsiveness among Jordanian patients. This study suggests that a significant association exists between the KCNA2 SNP rs3887820 and increased susceptibility to generalized myoclonic seizure. However, the present findings indicate that the KCNA1 and KCNV2 SNPs do not influence disease susceptibility and drug responsiveness in epileptic patients. Pharmacogenetic and case-control studies involving a multicenter and multiethnic approach are needed to confirm our results. To improve the efficacy and safety of epilepsy treatment, further studies are required to identify other genetic factors that contribute to susceptibility and treatment outcome.