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2.
Am J Pharm Educ ; 88(5): 100693, 2024 May.
Article in English | MEDLINE | ID: mdl-38574997

ABSTRACT

OBJECTIVE: Academic resilience, a critical determinant of academic achievement, is affected by various factors. There is a paucity of large-scale international assessments of academic resilience among pharmacy students. Therefore, this study aimed to assess academic resilience among pharmacy students in 12 countries and to evaluate factors associated with their academic resilience levels. METHODS: A cross-sectional online survey-based study was conducted among randomly selected pharmacy students in 12 countries: Egypt, Türkiye, Indonesia, Pakistan, Bangladesh, Iraq, Jordan, Nigeria, Malaysia, Saudi Arabia, Sudan, and the United Arab Emirates. After pilot testing, the validated 30-item academic resilience scale (ARS) was used for the assessment. The data were collected between November 1, 2022 and April 15, 2023. Descriptive and inferential statistics were performed, as appropriate. RESULTS: A total of 3950 were received from the 12 participating countries. The mean age was 21.68 ± 2.62 years. About two-thirds of the responses were from female participants and those studying for Bachelor of Pharmacy degrees. Overall, the findings show moderate academic resilience, which varied across countries. The median (IQR) of the total ARS-30 was 114 (103-124). Females exhibited lower negative affective and emotional response subscale levels than males. There were significant cross-country variations in the ARS-30 and all subscales. The highest overall levels were reported for Sudan, Pakistan, and Nigeria and the lowest were reported for Indonesia and Türkiye. Students in private universities tended to have higher overall ARS levels than public university students. Higher academic performance was significantly associated with ARS levels, whereas those with excellent performance exhibited the highest ARS levels. Students with exercise routines had higher ARS levels than those without exercise routines. Finally, students who were engaged in extracurricular activities had higher ARS levels than those who did not participate in these activities. CONCLUSION: The study offers insights into the factors affecting academic resilience in pharmacy students across several countries. The findings could guide interventions and support activities to improve resilience and academic outcomes.


Subject(s)
Resilience, Psychological , Students, Pharmacy , Humans , Students, Pharmacy/psychology , Students, Pharmacy/statistics & numerical data , Male , Female , Cross-Sectional Studies , Young Adult , Surveys and Questionnaires , Adult , Nigeria , Pakistan , Academic Success , Education, Pharmacy/statistics & numerical data , Egypt , Indonesia , Bangladesh , Jordan , Saudi Arabia , Malaysia , Iraq , Sudan
3.
Sci Rep ; 14(1): 1983, 2024 01 23.
Article in English | MEDLINE | ID: mdl-38263214

ABSTRACT

Artificial intelligence models, like ChatGPT, have the potential to revolutionize higher education when implemented properly. This study aimed to investigate the factors influencing university students' attitudes and usage of ChatGPT in Arab countries. The survey instrument "TAME-ChatGPT" was administered to 2240 participants from Iraq, Kuwait, Egypt, Lebanon, and Jordan. Of those, 46.8% heard of ChatGPT, and 52.6% used it before the study. The results indicated that a positive attitude and usage of ChatGPT were determined by factors like ease of use, positive attitude towards technology, social influence, perceived usefulness, behavioral/cognitive influences, low perceived risks, and low anxiety. Confirmatory factor analysis indicated the adequacy of the "TAME-ChatGPT" constructs. Multivariate analysis demonstrated that the attitude towards ChatGPT usage was significantly influenced by country of residence, age, university type, and recent academic performance. This study validated "TAME-ChatGPT" as a useful tool for assessing ChatGPT adoption among university students. The successful integration of ChatGPT in higher education relies on the perceived ease of use, perceived usefulness, positive attitude towards technology, social influence, behavioral/cognitive elements, low anxiety, and minimal perceived risks. Policies for ChatGPT adoption in higher education should be tailored to individual contexts, considering the variations in student attitudes observed in this study.


Subject(s)
Academic Performance , Artificial Intelligence , Humans , Universities , Anxiety , Students
4.
Saudi Pharm J ; 31(10): 101777, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37771957

ABSTRACT

Background: Corticosteroids (CS) are essential drugs in the treatment of several medical conditions. Assuming different roles, physicians and pharmacists play a primary role in prescribing and dispensing these medications to optimize patients' clinical management. The data on assessing knowledge and experience of healthcare professionals toward CS is scarce. Therefore, this study aimed to assess and compare knowledge, experience, and fears towards CS among Egyptian physicians and pharmacists. Methods: A cross-sectional, self-administrated, validated online questionnaire was used to collect the data from Egyptian healthcare professionals. The questionnaire consisted of four sections with multiple choice questions: sociodemographic (7 questions), knowledge about CS (13 questions), experience with CS prescription/dispensing (5 questions), and fears and preferences toward CS prescription/dispensing (13 questions). Descriptive and inferential statistics were used to analyze the data. Results: A total of 600 responses were analyzed in this study. The study sample was almost two-half of healthcare providers: 303 (50.5%) pharmacists and 297 (49.5%) physicians. Pharmacists had marginally higher knowledge scores as compared to those recorded for physicians (11.29 versus 10.16, respectively; P = 0.047). Physicians had more experience choosing corticosteroids in treatment plans based on their experience (51.8% vs 38.5%) and guideline recommendations (72.8% vs 50.9%) than pharmacists. However, pharmacists had more experience dealing with corticosteroid use based on patients' preferences (19.5% vs 4.9%) and showed a broader scope of experiencing side effects of corticosteroids with their patients. The two professions demonstrated high levels of fear, with pharmacists acknowledging significantly lower concerns about CS than physicians (3.72 versus 4.0, respectively; P = 0.003). Conclusion: Discrepancies exist among healthcare professionals in knowledge and experience, favoring better scientific knowledge of pharmacists related to corticosteroids. Based on these findings, the interprofessional collaborative efforts would provide comprehensive, patient-centered care that maximizes the benefits of CS while minimizing their risks.

5.
Front Pharmacol ; 14: 1185277, 2023.
Article in English | MEDLINE | ID: mdl-37214454

ABSTRACT

Objectives: Traumatic brain injury (TBI) is one of the top causes of morbidity and mortality worldwide. The review aimed to discuss and summarize the current evidence on the effectiveness of adjuvant neuroprotective treatments in terms of their effect on brain injury biomarkers in TBI patients. Methods: To identify relevant studies, four scholarly databases, including PubMed, Cochrane, Scopus, and Google Scholar, were systematically searched using predefined search terms. English-language randomized controlled clinical trials reporting changes in brain injury biomarkers, namely, neuron-specific enolase (NSE), glial fibrillary acid protein (GFAP), ubiquitin carboxyl-terminal esterase L1 (UCHL1) and/or S100 beta (S100 ß), were included. The methodological quality of the included studies was assessed using the Cochrane risk-of-bias tool. Results: A total of eleven studies with eight different therapeutic options were investigated; of them, tetracyclines, metformin, and memantine were discovered to be promising choices that could improve neurological outcomes in TBI patients. The most utilized serum biomarkers were NSE and S100 ß followed by GFAP, while none of the included studies quantified UCHL1. The heterogeneity in injury severity categories and measurement timing may affect the overall evaluation of the clinical efficacy of potential therapies. Therefore, unified measurement protocols are highly warranted to inform clinical decisions. Conclusion: Few therapeutic options showed promising results as an adjuvant to standard care in patients with TBI. Several considerations for future work must be directed towards standardizing monitoring biomarkers. Investigating the pharmacotherapy effectiveness using a multimodal biomarker panel is needed. Finally, employing stratified randomization in future clinical trials concerning potential confounders, including age, trauma severity levels, and type, is crucial to inform clinical decisions. Clinical Trial Registration: [https://www.crd.york.ac.uk/prospero/dis], identifier [CRD42022316327].

6.
Saudi Pharm J ; 31(3): 410-416, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36744104

ABSTRACT

Introduction: Grit is proposed as an essential trait for academic achievement. Thus, evaluating its current status and the associated factors could aid academic support planning. Objective: The present study aimed to assess grit level and its related factors among undergraduate pharmacy students from 14 countries amid the COVID-19 pandemic. Methods: A cross-sectional survey-based study was conducted among pharmacy students from 14 countries in Asia and the Middle East. A 31-item questionnaire was developed, validated, and pilot-tested, including the validated short scale for grit assessment. The data was collected between 1 February and 15 April 2022. Descriptive and inferential statistics were employed as appropriate. Results: A total of 2665 responses were received, mainly from females (68.7 %), living in urban areas (69.2 %) and studying at private universities (59.1 %). The average grit score on a scale of 5 was 3.15 ± 0.54. The responses revealed higher favourable responses to items on the perseverance of efforts (34.9 % to 54 %) compared to items on the consistency of interests (26.5 % to 31.1 %). Students who did not exercise (AOR: 0.47, 95 %CI: 0.33-0.67) or exercised irregularly (AOR: 0.64, 95 %CI: 0.45-0.90) were less likely to have higher grit scores than those who exercised regularly. Additionally, students who did not receive COVID-19 vaccination (AOR: 0.50, 95 %CI: 0.36-0.71) or received only one dose (AOR: 0.67, 95 %CI: 0.46-0.99) were less likely to have higher grit scores than those who received their booster vaccination. Interestingly, students who chose the pharmacy program as their only available or reasonable choice (AOR: 0.33, 95 %CI: 0.17-0.62) and students from public universities (AOR: 0.82, 95 %CI: 0.68-0.98) were less likely to have higher grit scores. On the other hand, students who did not face educational challenges with online learning (AOR: 1.19, 95 %CI: 1.003-1.416) and students with excellent (AOR: 2.28, 95 %CI: 1.57-3.31) and very good (AOR: 2.16, 95 %CI: 1.53-3.04) academic performance were more likely to have higher grit scores. Conclusion: The findings revealed moderate grit levels. Higher grit levels were thought to be associated with several personal, lifestyle and academic factors. Further interventions to support students' grit attributes are required, particularly concerning the consistency of interests.

7.
Healthcare (Basel) ; 11(2)2023 Jan 13.
Article in English | MEDLINE | ID: mdl-36673623

ABSTRACT

BACKGROUND: Corticosteroids play a significant role in managing the vast majority of inflammatory and immunologic conditions. To date, population-based studies on knowledge and attitudes concerning corticosteroids are scarce. This study aims to comprehensively assess knowledge, perception, experience and phobia toward corticosteroid use among the general population in the era of COVID-19. METHODS: A cross-sectional self-administrated questionnaire was used to collect the data from 6 countries. Knowledge and corticophobia scores, descriptive statistics and logistic regression were computed. RESULTS: A total of 2354 participants were enrolled in this study; the majority were females (61.6%) with an average age of 30. Around 61.9% had been infected previously with COVID-19, and about one-third of the participants had experience with corticosteroid use. The mean knowledge score was relatively satisfactory (8.7 ± 4.5 out of 14), and Corticophobia ranked a high score in all countries. Age, female gender, and history of COVID-19 were positively correlated with developing corticophobia. CONCLUSION: Our study highlights that the general knowledge about steroids was satisfactory. However, the phobia toward its use upon indication is high. Therefore, enhancing awareness and providing essential counseling regarding the rational use of corticosteroids may reduce corticophobia.

8.
Article in English | MEDLINE | ID: mdl-36361453

ABSTRACT

Controlling hypertension (HTN) remains a challenge, as it is affected by various factors in different settings. This study aimed to describe the disparities in the prevalence and barriers to hypertension control across countries of various income categories. Three scholarly databases-ScienceDirect, PubMed, and Google Scholar-were systematically examined using predefined search terms to identify potentially relevant studies. Original research articles published in English between 2011 and 2022 that reported the prevalence and barriers to HTN control were included. A total of 33 studies were included in this systematic review. Twenty-three studies were conducted in low and middle-income countries (LMIC), and ten studies were from high-income countries (HIC). The prevalence of hypertension control in the LMIC and HIC studies ranged from (3.8% to 50.4%) to (36.3% to 69.6%), respectively. Concerning barriers to hypertension control, patient-related barriers were the most frequently reported (n = 20), followed by medication adherence barriers (n = 10), lifestyle-related barriers (n = 8), barriers related to the affordability and accessibility of care (n = 8), awareness-related barriers (n = 7), and, finally, barriers related to prescribed pharmacotherapy (n = 6). A combination of more than one category of barriers was frequently encountered, with 59 barriers reported overall across the 33 studies. This work reported disparities in hypertension control and barriers across studies conducted in LMIC and HIC. Recognizing the multifactorial nature of the barriers to hypertension control, particularly in LMIC, is crucial in designing and implementing customized interventions.


Subject(s)
Hypertension , Humans , Prevalence , Hypertension/drug therapy , Hypertension/epidemiology , Hypertension/prevention & control , Medication Adherence , Income , Poverty
9.
Front Public Health ; 10: 1011376, 2022.
Article in English | MEDLINE | ID: mdl-36388263

ABSTRACT

Background: Pharmacy students will assume future roles as frontline healthcare providers. Therefore, evaluating their current state of mental wellbeing and its associated factors is essential for better planning students' support initiatives. This study aimed to assess mental wellbeing and its associated factors among undergraduate pharmacy students from 14 countries during the pandemic. Methods: A cross-sectional study was conducted among undergraduate pharmacy students in 14 countries in Asia and the Middle East. The validated Warwick-Edinburgh Mental Wellbeing Scale (the 14-item WEMWBS) was adopted to assess mental wellbeing. Data collection was performed online between February and April 2022. Descriptive and inferential statistics were used as appropriate. Results: A total of 2,665 responses were received, mainly from females (68.7%) with a higher presence of private universities (59.1%). About 34.9% had low mental wellbeing levels, while 57 and 8.1% had medium, and high levels, respectively. Binary logistic regression showed that males (AOR: 1.34; CI 95%: 1.11-1.61; p < 0.01) and students with no chronic illnesses (AOR: 2.01; CI 95%: 1.45-2.80; p < 0.001) were more likely to have higher mental wellbeing. Also, participants who did not engage in any exercise (AOR: 0.71; CI 95%: 0.52-0.98; p = 0.04) and those in public universities (AOR: 0.82; CI 95%: 0.69-0.97; p = 0.02) were less likely to have higher mental wellbeing. Additionally, students who had interest/passion for pharmacy (AOR: 1.69; CI 95%: 1.07-2.68; p = 0.02), and those who known pharmacists inspired (AOR: 1.81; CI 95%: 1.06-3.12; p = 0.03), were more likely to have higher mental wellbeing compared with those who had no specific reason for their choice to study pharmacy. The participants with excellent (AOR: 1.87; CI 95%: 1.29-2.70; p = 0.001) or very good self-reported academic performance (AOR: 1.57; CI 95%: 1.12-2.22; p = 0.01) were more likely to have higher mental wellbeing compared to those with fair academic performance. Conclusion: More than a third of the participants had low mental wellbeing. Various demographic, lifestyle, medical and academic factors appeared to affect students' mental wellbeing. Careful consideration of these factors and their integration into the pharmacy schools' plans for student support services and academic advising would be essential to improve students' mental wellbeing.


Subject(s)
Students, Pharmacy , Male , Female , Humans , Cross-Sectional Studies , Universities , Mental Health , Life Style
10.
Front Pharmacol ; 13: 944392, 2022.
Article in English | MEDLINE | ID: mdl-36249765

ABSTRACT

Background: The pain pattern after laparoscopic cholecystectomy (LC) is complex and distinct from postoperative pain after other laparoscopic procedures, suggesting that procedure-specific optimal analgesic management plans should be proposed. Duloxetine, a non-opioid neuromodulator, has been widely used to manage pain with dual central and peripheral analgesic properties. Aims: To assess the effect of preoperative administration of duloxetine compared to placebo on postoperative pain control in patients undergoing LC. Patients and Methods: This study was a randomized, parallel-group, placebo-controlled, double-blinded study performed on patients undergoing LC. Patients were randomly divided into two groups of 30 each on the day of surgery in the preoperative holding area, using a computer-generated random number to receive 60 mg duloxetine as a single oral dose 2 h before the procedure or placebo. The primary outcome was the difference in the mean of visual analogue scale (VAS) scores between the two studied groups, as measured by the area under the curve (AUC) of the VAS scores. Results: The derived AUC of VAS scores in the duloxetine group (757.89 ± 326.01 mm × h) was significantly lower than that calculated for the control group (1005.1 ± 432.5 mm × h). The mean postoperative VAS scores recorded at 4 and 24 h were statistically different between the study groups (p = 0.041 and 0.003, respectively). As observed in the survival curve analysis, there was no significant difference (p = 0.665) for the time until the patient's first request for rescue medications in the two groups. The frequency of postoperative nausea and vomiting (PONV) was lower in patients of the duloxetine group than that recorded in those allocated to the control group at 8 and 24-h time intervals (p = 0.734 and 0.572, respectively). Conclusion: Preoperative use of duloxetine reduces postoperative pain significantly compared with placebo. In addition, its use is associated with a reduction in PONV. These preliminary findings suggest that duloxetine could play a role in the acute preoperative period for patients undergoing LC. Clinical Trial Registration: [https://clinicaltrials.gov/ct2/show/NCT05115123, identifier NCT05115123].

11.
Int J Clin Pract ; 75(11): e14807, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34487412

ABSTRACT

BACKGROUND AND AIM: Rifaximin is an oral antibiotic with promising efficacy in the reduction of hepatic encephalopathy (HE) recurrence. Development of microbial resistance to rifaximin is not studied yet in HE. The study aim was to assess the microbial resistance, safety and efficacy of rifaximin as secondary prophylaxis of HE. METHOD: In this open-label parallel, prospective interventional study, 100 patients were randomly allocated either to receive 400 mg rifaximin 3 times/d plus 30-45 mL lactulose 3 times/d (intervention group) or to receive the standard of care only which is lactulose alone (control group) for 6 months. The primary outcome of the study was the difference between minimum inhibitory concentration (MIC) of rifaximin among the two studied groups at the end of treatment. The secondary outcomes included the time to first episode of HE, time to first hospitalisation, and patient's survival. RESULTS: The MIC did not differ significantly after treatment exposure compared with baseline either between groups or within the same group. The time to new episode of HE was 18.84 ± 6.49 weeks (mean ± SD) in the intervention group and was significantly longer (P = .002) than that in the control group 14 ± 7.52 weeks. Moreover, only 23 (46%) patients developed overt HE in the intervention group compared with 35 patients (70%) in the control group (P = .005). Also, there was an observed 32% reduction in the risk of hospitalisation in intervention group compared with control group. CONCLUSION: Rifaximin succeeded to maintain remission from new episodes of HE in hepatitis C virus cirrhotic patients with limited potential for development of microbial resistance over the study period. ClinicalTrials.gov Identifier: NCT04736836.


Subject(s)
Hepacivirus , Hepatic Encephalopathy , Gastrointestinal Agents/therapeutic use , Hepatic Encephalopathy/drug therapy , Hepatic Encephalopathy/prevention & control , Humans , Liver Cirrhosis/complications , Liver Cirrhosis/drug therapy , Prospective Studies , Rifaximin/therapeutic use
12.
Front Pharmacol ; 12: 675948, 2021.
Article in English | MEDLINE | ID: mdl-34276366

ABSTRACT

Background: Terlipressin is the first-line pharmacological treatment for hepatorenal syndrome. When terlipressin is unavailable, midodrine/octreotide or norepinephrine, with albumin, represent the alternative treatments. The comparative efficacy of these alternative regimens remains unclear. Objective: To compare the efficacy of midodrine/octreotide to that of norepinephrine for the treatment of patients with hepatorenal syndrome. Methods: In the intensive care setting, sixty patients with hepatorenal syndrome were randomized to initially receive either 0.5 mg/h of norepinephrine (maximum 3 mg/h) or 5 mg of oral midodrine three times/day (maximum 12.5 mg three times/day) plus octreotide (100 µg/6 h) as subcutaneous injection (maximum 200 µg/6 h), together with albumin (20-40 g/day). Treatment was allowed for a maximum of 10 days. Survival was analyzed for up to 30 days. The primary efficacy outcome was the proportion of patients who achieved full response, defined as the return of serum creatinine to a value within 0.3 mg/dl of the baseline at the end of treatment. Results: There was a significantly higher rate of full response in the norepinephrine group (15/26, 57.60%) than the midodrine/octreotide group (5/25, 20%) (p = 0.006). Eleven (42.30%) patients in the norepinephrine group and 6 (24%) in the midodrine/octreotide group survived (p = 0.166). Conclusion: Norepinephrine plus albumin is significantly more effective than midodrine and octreotide plus albumin in improving renal function in patients with hepatorenal syndrome. (ClinicalTrials.gov, identifier: NCT03455322). https://clinicaltrials.gov/ct2/show/NCT03455322?cond = Hepatorenal+Syndrome&cntry = EG&draw = 2&rank = 1.

13.
Biomed Pharmacother ; 140: 111725, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34015580

ABSTRACT

BACKGROUND: Pain after laparoscopic cholecystectomy remains a major challenge. Ondansetron blocks sodium channels and may have local anesthetic properties. AIMS: To investigate the effect of intraperitoneal administration of ondansetron for postoperative pain management as an adjuvant to intravenous acetaminophen in patients undergoing laparoscopic cholecystectomy. METHODS: Patients scheduled for elective laparoscopic cholecystectomy were randomized into two groups (n = 25 each) to receive either intraperitoneal ondansetron or saline injected in the gall bladder bed at the end of the procedure. The primary outcome was the difference in pain from baseline to 24-h post-operative assessed by comparing the area under the curve of visual analog score between the two groups. RESULTS: The derived area under response curve of visual analog scores in the ondansetron group (735.8 ± 418.3) was 33.97% lower than (p = 0.005) that calculated for the control group (1114.4 ± 423.9). The need for rescue analgesia was significantly lower in the ondansetron (16%) versus in the control group (54.17%) (p = 0.005), indicating better pain control. The correlation between the time for unassisted mobilization and the area under response curve of visual analog scores signified the positive analgesic influence of ondansetron (rs =0.315, p = 0.028). The frequency of nausea and vomiting was significantly lower in patients who received ondansetron than that reported in the control group (p = 0.023 (8 h), and 0.016 (24 h) respectively). CONCLUSIONS: The added positive impact of ondansetron on postoperative pain control alongside its anti-emetic effect made it a unique novel option for patients undergoing laparoscopic cholecystectomy.


Subject(s)
Acetaminophen/therapeutic use , Adjuvants, Pharmaceutic/therapeutic use , Analgesics/therapeutic use , Antiemetics/therapeutic use , Cholecystectomy, Laparoscopic , Ondansetron/therapeutic use , Pain, Postoperative/drug therapy , Serotonin Antagonists/therapeutic use , Adult , Double-Blind Method , Female , Humans , Infusions, Intravenous , Injections, Intraperitoneal , Male , Middle Aged , Postoperative Nausea and Vomiting/drug therapy
14.
Article in English | MEDLINE | ID: mdl-27802917

ABSTRACT

Individualized therapy is a recent approach aiming to specify dosage regimen for each patient according to its genetic state. Cancer chemotherapy requires continuous monitoring of the plasma concentration levels of active forms of cytotoxic drugs and subsequent dose adjustment. In order to attain optimum therapeutic efficacy, correlation to pharmacogenetics data is crucial. In this study, a specific, accurate and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) has been developed for determination of methotrexate (MTX), 6-mercaptopurine (MP) and its metabolite 6-thioguanine nucleotide (TG) in human plasma. Based on the basic character of the studied compounds, solid phase extraction using a strong cation exchanger was found the optimum approach to achieve good extraction recovery. Chromatographic separation was carried out using RP-HPLC and isocratic elution by acetonitrile: 0.1% aqueous formic acid (85:15v/v) with a flow rate of 0.8mL/min at 40°C. The detection was performed by tandem mass spectrometry in MRM mode via electrospray ionization source in positive ionization mode. Analysis was carried out within 1.0min over a concentration range of 6.25-200.00ng/mL for the studied analytes. Validation was carried out according to FDA guidelines for bioanalytical method validation and satisfactory results were obtained. The applicability of the assay for the monitoring of the MTX, MP and TG and subsequent application to personalized therapy was demonstrated in a clinical study on children with acute lymphoblastic leukemia (ALL). Results confirmed the need for implementation of reliable analysis tools for therapeutic dose adjustment.


Subject(s)
Antimetabolites, Antineoplastic/blood , Mercaptopurine/blood , Methotrexate/blood , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Thioguanine/blood , Child , Chromatography, High Pressure Liquid/methods , Humans , Limit of Detection , Polymorphism, Genetic , Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Solid Phase Extraction/methods , Tandem Mass Spectrometry/methods
15.
Pediatr Blood Cancer ; 63(9): 1539-45, 2016 09.
Article in English | MEDLINE | ID: mdl-27163515

ABSTRACT

BACKGROUND: The aim of the present study is to determine the correlation of hepatitis C virus (HCV) infection and polymorphisms in different genes with toxicity of either methotrexate (MTX) or 6-mercaptopurine (6-MP) administered to children with acute lymphoblastic leukemia (ALL). PROCEDURE: One hundred children with low-risk ALL, who were treated according to the St. Jude Total therapy XV, were recruited. The recruited children were receiving MTX and 6-MP during maintenance phase. Patients were excluded from the study if they had other types of leukemia. Genotyping analyses for the thiopurine methyltransferase (TPMT), methylenetetrahydrofolate reductase (MTHFR), and glutathione S-transferase (GST) genes were performed using a combination of polymerase chain reaction (PCR) and PCR-RFLP (where RFLP is restriction fragment length polymorphism) protocols. Relevant clinical data on adverse drug reactions were collected objectively (blinded to genotypes) from the patient medical records. RESULTS: There was a significant correlation between the combined presence of HCV and TPMT*3B G460A gene polymorphisms and grades 2-4 hepatotoxicity as aspartate aminotransferase (AST) elevation (P < 0.04). The same observation was seen when comparing either the presence of HCV alone or the presence of the gene polymorphism alone. A significant association between the combined presence of HCV and MTHFR C677T polymorphism and grades 2-4 hepatotoxicity as alanine aminotransferase (ALT), AST, and alkaline phosphatase (ALP) elevation was observed (P values <0.001, 0.02, and 0.001, respectively). The presence of HCV infection had a significant negative effect on hepatic transaminases. CONCLUSIONS: The present data support a role for combining analysis of genetic variation in drug-metabolizing enzymes and the presence of HCV in the assessment of specific drugs toxicities in multiagent chemotherapeutic treatment regimens.


Subject(s)
Hepacivirus/isolation & purification , Mercaptopurine/adverse effects , Methotrexate/adverse effects , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Child , Child, Preschool , Female , Genotype , Humans , Liver/drug effects , Male , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Methyltransferases/genetics , Polymorphism, Genetic , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/virology
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