Prevalence of Medication Associated with QTc Prolongation Used Among Critically Ill Patients.

Background: Acquired prolonged corrected QT (QTc) interval can lead to life-threatening Torsade de Pointes (TdP) arrhythmia. Multiple risk factors including medications, comorbidities, and electrolyte imbalances contribute significantly to acquired manifestations of the QTc prolongation. Critically ill patients are particularly more vulnerable to TdP due to complex medical conditions, aging, and polypharmacy. Objective: This study aimed to assess the prevalence of TdP-associated medication prescribing, identify risk factors for QTc prolongation and TdP, and determine primary predictors of high TdP medication usage in critically ill patients in Jordan. Methods: We conducted a retrospective cross-sectional analysis of electronic medical records for patients from King Abdullah University Hospital who were admitted to Intensive Care Unit (ICU) between (July 2012-July 2022). We collected data on patients' demographics, clinical characteristics, comorbidities, laboratory results, and prescribed medications. Medications were categorized into three TdP risk levels according to CredibleMeds® assessment tool. Data were analyzed using descriptive statistics and a binary logistic regression model. Results: Of the 13,300 patients (58.2% male, median age 62 years). Prescribing prevalence for medications with known TdP risk was 19%, possible risk (24.7%), conditional risk (21.6%), and confirmed conditional risk (8.3%). Common comorbidities included hypertension (40.9%), diabetes (33.3%), and cancer (15.4%). Drugs with known TdP risk included citalopram, amiodarone, clarithromycin, and ciprofloxacin. A binary regression model revealed that as age increased, the odds of TdP associated medication prescribing decreased (OR = 0.989, p < 0.001), while patients on more than five medications had higher odds (OR = 4.281, p < 0.001). Conclusion: The study identified a notable prevalence of prescribing for medications with QTc prolongation/TdP risk in critically ill patients. Healthcare providers in the ICU should exercise caution to minimize the inadvertent prescription of TdP associated medications especially among older patients and those with polypharmacy.

Adherence and utilization of short-term antibiotics: Randomized controlled study.

Enhancing adherence to medication has the potential to improve clinical outcomes and decrease healthcare cost. The role of clinical pharmacist-led education on adherence to short-term antibiotic has never been investigated in Jordan. This study aimed to evaluate the impact of an educational intervention on antibiotic short-term adherence and to assess the antibiotic utilization pattern. A prospective, single blinded, randomized controlled study was conducted in a tertiary referral hospital in Jordan. Adult patients diagnosed with acute infection and prescribed a short-term antibiotic course (< 30 day) were included in the study. Recruited patients were randomly allocated into control and intervention groups. Pharmaceutical education about the correct use of antibiotic/s was provided to the intervention group. The results showed that penicillins were the most prescribed antibiotics (38.7%) followed by fluoroquinolones (23.9%) and cephalosporines (20.9%). Patients in the intervention group were more likely to be adherent to the prescribed antibiotics compared to control group (OR = 1.445, 95CI% = 1.029-2.030, p = 0.033). Employed patients, less frequent administration of antibiotic, and searching information related to the prescribed antibiotics were factors associated with better adherence to short-term antibiotic (p<0.05). The most common reasons for non-adherence were feeling better and forgetfulness to take medication. These findings highlighted that pharmacist-led educational intervention significantly enhance adherence to prescribed short-term antibiotics which is a major drive to control antibiotic resistance. Initiatives should be adopted to include patient education as a regular element in the medication dispensing process. Clinical trial registration: The trial is registered at ClinicalTrials.gov (identifier: NCT05293977).

Students' experiences and attitudes toward a newly developed simulation-based pharmaceutical care clinical rotation: A pre-post study design.

Purpose: This study aims to evaluate Doctor of Pharmacy (PharmD) students' experience with the newly developed simulation-based pharmaceutical care (PC) rotation by evaluating their knowledge and attitudes towards PC before and after the rotation. Methods: A self-administered questionnaire was distributed to sixth year PharmD students enrolled in the clinical training rotation "Comprehensive Pharmaceutical Care" during the 2020/2021 academic semesters at Jordan University of Science and Technology's (JUST) Faculty of Pharmacy. Questionnaires were distributed before and after completing four experiential training weeks and consisted of three sections. The first section collected students' demographic details while the second and third sections evaluated students' knowledge about, and attitudes toward PC, respectively. Descriptive statistics were used to describe and compare changes in students' knowledge and attitudes pre-and post-rotation. Results: A total of 106 valid questionnaires were completed with a response rate of 99.07%. The rates of correct answers increased after the rotation with median total knowledge score increasing from 8 to 10 (out of 13, P value < 0.001). Significant improvements in students' understanding of aspects relating to the concept and process of PC, and the role of clinical pharmacist in PC provision, were shown post the simulation-based clinical rotation. Similarly, their attitudes toward performing PC were either improved or emphasized. In contrast results also revealed that specific aspects of the rotation require further refinement, such as the comprehensiveness of the PC process and responsibilities in providing PC. Conclusions: PharmD students' understanding and attitudes toward PC were either improved or emphasized after the simulation-based PC rotation. This study highlights the value of simulation as a unique instructional technique that can assist educators to develop PC competencies for pharmacy students.

Preparation of Modified Chitosan-based Nanoparticles for Efficient Delivery of Doxorubicin and/or Cisplatin to Breast Cancer Cells.

PURPOSE: The aim is to develop a novel pH-responsive modified chitosan-based nanoparticles system for active loading of doxorubicin (DOX) and triggered intracellular release. METHODS: Nanoparticles were formed in an aqueous medium via ionic interaction between negatively charged chitosan derivative and positively charged DOX at neutral pH and then transformed in situ into cisplatin (CIS) cross-linked nanoparticles through cross-linking the formed micelles via chelation interaction between the negatively charged polymeric carrier and cisplatin. Nanoparticles were characterized in terms of particle size and zeta potential using DLS and TEM. Drug loading efficiency and encapsulation efficiency were determined based on the physio-chemical proprieties of the polymer and the amount of the cross-linking agent. In vitro release studies were performed using the dialysis method at different pHs. Finally, the cytotoxic effects of these nanoparticles were performed against the MCF-7 BrCA cell line under different pHs. RESULTS: The average particle size of polymer alone and DOX nanoparticles was 277.401 ± 13.50 nm and 290.20 ± 17.43 nm, respectively. The zeta potential was -14.6 ± 1.02 mV and -13.2 ± 0.55 mV, respectively, with a low polydispersity index. Drug loading and encapsulation deficiencies were determined, dependent on the amount of the cross-linking agent. In vitro release studies showed that the release of DOX from these nanoparticles was pH-dependent. Moreover, results showed that the cytotoxicity magnitude of DOX-loaded nanoparticles against MCF-7 BrCA cells was higher compared with free DOX. CONCLUSION: These novel pH-sensitive nanoparticles proved to be a promising Nano-drug delivery for tumor-targeted delivery of DOX.

Crizotinib induced antitumor activity and synergized with chemotherapy and hormonal drugs in breast cancer cells via downregulating MET and estrogen receptor levels.

MET is a receptor tyrosine kinase known to drive neoplastic transformation and aggressive tumor phenotypes. Crizotinib is an oral multi-targeted tyrosine kinase inhibitor of MET, ALK, RON, and ROS1 kinases. In this study, the anticancer effects of crizotinib on breast cancer cells were investigated in vitro along with the molecular mechanisms associated with these effects. Besides, the antiproliferative effects of crizotinib in combination with chemotherapy, hormonal drugs, and targeted agents were examined. Results showed that crizotinib produced dose-dependent antiproliferative effects in BT-474 and SK-BR-3 breast cancer cells with IC50 values of 1.7 µM and 5.2 µM, respectively. Crizotinib inhibited colony formation of BT-474 cells at low micromolar concentrations (1-5 µM). Immunofluorescence and Western blotting indicated that crizotinib reduced total levels of MET and estrogen receptor (ERα) in BT-474 cells. Also, crizotinib reduced the levels of phosphorylated (active) MET and HER2 in BT-474 cells. The combined treatment of crizotinib with doxorubicin and paclitaxel resulted in synergistic growth inhibition of BT-474 cells with combination index values of 0.46 and 0.35, respectively. Synergy was also observed with the combination of crizotinib with the hormonal drugs 4-hydroxytamoxifen and fulvestrant in BT-474 cells. Alternatively, the combination of crizotinib with lapatinib produced antagonistic antiproliferative effects in both BT-474 and SK-BR-3 cells. Collectively, these findings demonstrate the anticancer effects of crizotinib in breast cancer cells and reveal ERα as a potential therapeutic target of the drug apart from its classical kinase inhibitory activity. Crizotinib could be an appealing option in combination with chemotherapy or hormonal drugs for the management of breast cancer.

Physicians' Attitudes and Ethical Obligations to Pharmacogenetic Testing.

INTRODUCTION: Despite the increased utilization of pharmacogenetic (PGt) testing to guide drug therapy, little is known about the ethical challenges posed by the use of these genetic tools. METHODS: This cross-sectional study aimed to address ethical issues related to ancillary genetic information, consent forms, and potential confidentiality breaches from physicians' perspectives. A questionnaire was administered to all practicing physicians working in KAUH. RESULTS: Almost 49% and 65% of physicians were willing to recommend PGt testing for adult and pediatric patients, respectively. The findings showed that physicians attitudes towards the clinical utility of PGt testing became more preceptive. The majority (73.7%) indicated that PGt testing should not be treated as other routine laboratory tests. The finding also focused on potential conflicts regarding ancillary genetic information, in which 78.8% indicated that they would like to preserve the confidentiality and privacy of the patients and only 14.4% of physicians did not feel obligated to let patients know about any future risk that might be uncovered using PGt testing. The findings showed that collecting both verbal and written consents was imperative prior to testing. Seriousness and predictability of the diseases were reported to be legitimate circumstances that allow disclosure of genetic information. DISCUSSION: Unless the field of PGt testing addresses the ethical challenges that might be encountered during PGt treatment, these issues might influence its acceptance in routine clinical settings. Establishing a minimal set of ethical standards may help emphasize the role of physicians and thus facilitate the implementation of PGt tests.

Fresh Pomegranate Juice Decreases Fasting Serum Erythropoietin in Patients with Type 2 Diabetes.

Pomegranate juice (PJ) has been recognized to have various biological benefits in several pathological conditions. One such benefit is the augmentation of hemoglobin level and the number of erythrocytes in the human body. Here, we assessed the short-term effect of fresh PJ on the level of Erythropoietin (EPO) in patients with type 2 diabetes (T2D) compared to healthy individuals. Blood samples from 59 participants with T2D and 30 healthy individuals were collected after a 12-hour fast and 3 hours after administration of fresh PJ at 1.5 mL per kg body weight. Serum glucose was measured by standard method and commercially available chemiluminescent immunoassay kits were used to determine serum EPO concentration. Mean changes in serum EPO levels 3 hours after ingesting PJ and before the juice ingestion (EPO response to PJ) for both diabetic and healthy participants were -2.002 ± 0.541 vs. - 0.041 ± 0.214, respectively (P = 0.0087). This EPO response to PJ was found not to be correlated with age (P = 0.6622) and gender (P = 0.5354) for patients with T2D, while a negative correlation (P = 0.0183) between EPO response to PJ and fasting serum glucose concentrations was observed in these patients. In conclusion, fresh PJ reduced serum EPO level in patients with T2D, but not in healthy individuals, 3 hours after ingesting the juice. The EPO response to PJ was found to be negatively correlated with fasting serum glucose, but not with age and gender, of patients with T2D. This trial is registered with ClinicalTrials.gov Identifier. NCT03902288.

Immunomodulatory effect of statins on Regulatory T Lymphocytes in human colorectal cancer is determined by the stage of disease.

Colorectal cancer (CRC) is a public health problem worldwide and in Jordan. Statins are cholesterol lowering agents. Beyond their effects, statins use has been reported to reduced risk of several malignances, including CRC. This study aimed to assess the effect of statins on CRC by studying cellular infiltration of Regulatory T Lymphocytes (Tregs) into CRC tissues and their effect on Transforming growth factor beta 1 (TGF-ß1) level and on angiogenesis. Fourty seven specimens (25 statins users vs. 22 non-users) were used. Immunohistochemistry was performed to study Tregs infiltration using their marker, fork head transcription factor, and angiogenesis using CD31 as a marker. TGF-ß1 levels were measured using ELISA. Results revealed that statins use was associated with more Tregs infiltration, less angiogenesis but no difference in TGF-ß1 content in tumor tissue. When results were further stratified according to stage of disease, more Tregs infiltration was significantly noticed in advanced disease but not in early disease. In addition, more angiogenesis inhibition was noticed in early disease but not in advanced disease. Same stage-dependence wasn't noticed with TGF-ß1 expression. In early disease, reduction of angiogenesis mediated by statins might lead to reduction of tumor aggressiveness. On the other hand, Tregs infiltration into tumor mediated by statins might reduce cancer aggressiveness in advanced disease. These results suggest that statins might be used in the treatment of CRC.

Investigating the Effect of Demographics, Clinical Characteristics, and Polymorphism of MDR-1, CYP1A2, CYP3A4, and CYP3A5 on Clopidogrel Resistance.

Clopidogrel is an antiplatelet agent that is indicated for cardiovascular emergencies and procedures. The drug, however, is subject to response variability leading to therapy resistance. In this research, we explored the demographic, clinical, and genetic factors associated with clopidogrel resistance. Data analysis among our 280 subjects receiving clopidogrel showed some risk factors that are significantly associated with clopidogrel resistance compared with responders. Those were: female sex (P = 0.021), advanced age (P = 0.011), obesity (P = 0.002), and higher body mass index (P = 0.008) and higher platelets count (P = 0.002). However, known polymorphisms of MDR-1, CYP1A2, CYP3A4, and CYP3A5 were not associated with treatment resistance when compared to responders to clopidogrel therapy. Knowledge about such risk factors might provide recommendation in the future about starting doses or monitoring recommendations.

Evaluation of the Effect of Uremic Serum on Hepatic Reductase Functional Expression.

BACKGROUND: The nonrenal clearance of drugs mediated by hepatic reduction is selectively altered by kidney disease. This study evaluated the influence of uremic serum on the expression and activity of reductase enzymes. METHODS: Human hepatocellular carcinoma cells (HepG2) were incubated with 5% pooled serum collected from patients with hemodialysis (pre- and post-dialysis session) or control subjects. The mRNA expression of various aldo-keto (AKR1C) and carbonyl (CBR) reductases were measured. Reductase metabolic activity was assessed in human liver cytosol or HepG2 cells using naltrexone as a substrate. RESULTS: Incubation of cells with pre-dialysis serum resulted in significant upregulation of AKR1C4 (by 63.2%) and CBR1 (by 34.6%) versus control serum. This increase was not observed for AKR1C1 and CBR1 with serum collected post-dialysis. While uremic serum had no effect on reductase activity, some instances with differences in metabolite formation among individual's pre- and post-dialysis samples were observed. CONCLUSION: Although uremic serum can upregulate mRNA expression of several reductases, this effect was not observed at the activity level. Future studies are necessary to improve our understanding of the mechanistic effects of impaired kidney function on drug reduction.

Knowledge and Awareness of Colorectal Cancer Early Warning Signs and Risk Factors among University Students in Jordan.

In the present study, we aimed to assess the level of awareness regarding CRC warning signs and risk factors among undergraduate students. A cross-sectional survey using standardized questionnaire developed by the Cancer Research Center in the UK was carried out in three different public universities in Jordan including Jordan University of Science and Technology, Yarmouk University, and AL al-Bayt University over a 5-month period. Volunteers were asked about their knowledge regarding CRC symptoms, risk factors, and their behaviors regarding seeking medical advice. Findings revealed that response rate was 80.1%. Vast majority of responders were female (70.9%) and 18.2% of them were studying medical-related specialties. Regarding CRC symptoms, 14.3% of responders experienced poor knowledge, 52.9% have fair knowledge, and 32.8% have good knowledge. Abdominal pain was the most recognized warning signs where 70.8% of responders could recall it. In addition, risk factors awareness was lower than warning signs awareness. About 36.1% of responders have poor knowledge, 47.4% had fair knowledge, and 16.5% had good knowledge. Unhealthy diet was the most recognized risk factor where 32.3% of responders could recall it. Moreover, females were more aware regarding CRC symptoms. Similar findings were obtained for participants who were aged 20 years or more and for those who had previous experience of cancer. Students who were studying medical-related specialties were more aware of both CRC symptoms and risk factors than those who studying other specialties. Furthermore, regarding time to seek medical attention we found that 60.6% of volunteers would seek medical advice within 1 week of noticing CRC symptoms and 12% would seek it within 2 weeks. The mean duration for seeking medical advice was found to be 1.9 weeks. University students' awareness level of CRC is poor, and therefore, extended attention should be attempted to enhance the awareness of CRC via continuous education programs, lectures, or campaigns to encourage the early detection CRC.

A mini-review of c-Met as a potential therapeutic target in melanoma.

Melanoma is the third highest rated cancer in prevalence. Surgery, radiotherapy and targeted/biological therapies in addition to chemotherapy are available options for management of this cancer. Met is an appealing target for management of this type of cancer, since it targets many cancer vital processors, such as angiogenesis, cell growth, scattering and differentiation. In this review, we provide an overview about pathway abnormalities associated with melanoma. We also provide a summary about the events involved in Met signaling and related signaling molecules. We also show the evidence of the importance of Met signaling pathway as a target in cancer management. We also summarize clinical evidence about the use of Met signaling in management of cancer and summarize available trials related to targeting Met in other cancers.

Changes in the expression and protein level of matrix metalloproteinases after exposure to waterpipe tobacco smoke.

Waterpipe smoking has become a worldwide epidemic with health consequences that only now are beginning to be understood fully. Because waterpipe use involves inhaling a large volume of toxicant-laden smoke that can cause inflammation, some health consequences may include inflammation-mediated lung injury. Excess matrix metalloproteinase expression is a key step in the etiology of toxicant exposure-driven inflammation and injury. In this study, changes in the level and mRNA of major matrix metalloproteinases (MMP-1, -9, and -12) in the lungs of mice following exposure to waterpipe smoke were investigated. Balb/c mice were exposed to waterpipe smoke for one hour daily, over a period of 2 or 8 weeks. Control mice were exposed to fresh air only. ELISA and real-time PCR techniques were used to determine the protein and mRNA levels of MMP-1, -9, and -12 in the lungs. Our findings showed that MMP-1, -9, and -12 levels in the lung significantly increased after both 2 (p < 0.05) and 8 weeks (p < 0.01) exposures. Similarly, RT-PCR findings showed that mRNA of those proteinases significantly increased following 2 (p < 0.01) and 8 weeks (p < 0.001) exposures. In conclusion, waterpipe smoking is associated strongly with lung injury as measured by elevation in the expression of MMPs in the lung tissue.

An audit on public awareness of depression symptoms in Jordan.

OBJECTIVES: Depression is a common mental health disorder. The aim of this study is to determine the level of public awareness regarding this illness, its symptoms, associated factors, available forms of treatment, and the attitude towards depressed people. METHODS: A self administered questionnaire was filled in by approximately 5000 individuals selected from various regions of Jordan. RESULTS: The majority of participants thought that depression is a treatable condition that can affect patient at any age, and may be controlled by the will power. Loss of interest in things and presence of negative feelings were the most commonly recognized symptoms of depression, while, unemployment and poverty were found to be the most recognized risk factors for depression. In addition, most participants considered support from family and friends (93.6%) as well as exercise (80.4%) to be the best available forms of depression treatment. Respondents found it acceptable to work, make friends with, or marry depressed individuals. The first choice persons for seeking help by most participants were family members and friends (49.8%). CONCLUSION: Collectively, the level of awareness of depression was acceptable. However, further efforts are necessary to establish public educational programs related to depression in order to raise awareness regarding the disease.

Etiologies of acute renal failure in a sample of hospitalized Jordanian patients.

Review of literature revealed no studies about the predominant causes and risk factors of acute renal failure in Jordan. This study identifies the most common causes of acute renal failure and the possible risk factors among hospitalized Jordanian population. A total of 111 patients were admitted to both King Abdullah University Hospital and Princess Basmah Teaching Hospital from December 2005 to April 2006 with a diagnosis of acute renal failure or developed acute renal failure in hospital during their stay. A written form was filled from the patients and their files. Results showed that 31.5% of patients were diabetic, 44.1% were hypertensive, and 40.5% had preexisting chronic renal failure. On admission, creatinine blood levels were high in 97 patients (87.4%), while at discharge, they were high in 61 patients (55%). Urgent dialysis was done for 20 patients (18%). In all, 95 patients (85.6%) were discharged home, and 16 patients (14.4%) died in hospital. Causes of acute renal failure included dehydration, diuretics, sepsis, contrast media, nonsteroidal anti-inflammatory drugs, glomerulonephritis, systemic lupus erythematosus, stones, and others. In conclusion, one-third of the causes of acute renal failure in this sample of hospitalized Jordanian patients were due to drugs, which makes this problem preventable. Mortality was affected by the age of patients and the duration of hospitalization.

Etiologies of chronic renal failure in Jordanian population.

BACKGROUND: Chronic renal failure (CRF) is a major medical problem, not only because of its prevalence, but also because of its complications, which have a huge impact on a person's life, both mentally and socially. By investigating the etiologies predisposing patients to CRF, we might be able to give recommendations about what should be done to avoid it. METHODS: A questionnaire was filled in from patients who presented with CRF to 2 major hospitals in Irbid, Jordan, investigating the causes and risk factors for CRF available in those patients. RESULTS: A total of 235 patients were diagnosed with CRF in 2 major hospitals in Irbid, Jordan. Around 72.8% of these patients were older than 40 years, 53.6% were females. Diabetes mellitus was the leading cause of CRF (44.7%); the second cause was glomerulonephritis (9.8%); and chronic use of nonsteroidal antiinflammatory drugs (NSAIDs) was the third cause (8.9%). CONCLUSION: A large percentage of patients had CRF due to diabetes. We provide evidence that our prescriptions must be revised, as chronic use of NSAIDs was the third leading cause of CRF. Both of these causes are seemingly preventable, and efforts should be made to eliminate them from the list of etiologies.

Self-medication with antibiotics in Jordanian population.

OBJECTIVES: A survey was conducted to estimate the prevalence of self-medication with antibiotics in Jordan and evaluate the factors associated with antibiotic misuse. METHODS: Validated questionnaire was used to collect data from a sample of 1943 households (9281 persons) selected from among different cities in Jordan. RESULTS: 842 (39.5%) of 2133 antibiotic users identified via the survey had used antibiotics without a prescription within a one-month study period. Self-medication with antibiotics was found to be significantly associated with age, income, and level of education. The main reason for self-medication as reported by the participants was their previous experience on the efficacy of treatment. The main sources of antibiotics were the previously prescribed pharmaceuticals stored in the household and those purchased in pharmacies. CONCLUSION: The prevalence of self-medication with antibiotics in Jordan is alarmingly high. Given the growing global resistance to antibiotics and the documented health problems related to their inappropriate use, our findings may have major public health policy implications in Jordan.