Synergistic effect of venetoclax and teglicar in multiple myeloma cell lines

Multiple myeloma is a hematological malignancy characterized by the clonal proliferation of plasma cells. Recent advancements in treatment strategies have led to a significant shift in the management of this malignancy. Venetoclax, an apoptosis inducer, has emerged as a promising therapeutic option for multiple myeloma. Fatty acid oxidation (FAO) is one of the metabolic reprogramming events that occurs because of mutations in certain genes and thus plays a crucial role in cancer progression. Teglicar, a reversible inhibitor of FAO, targets carnitine palmitoyl transferase 1 (CPT1) and has shown potential in cancer treatment due to its interaction with apoptotic regulators such as Bcl-2. In this study we investigated the in vitro anti-cancer activity of teglicar, in myeloma cell lines (RPMI 8226 and U266B1). Our findings revealed a significant inhibition of RPMI 8226 cell viability with an IC50 = 50 µM, but at a higher concentration for U266B1 cells. Notably, the combination of teglicar with venetoclax showed a synergistic effect. Although both cell lines were known to be resistant to venetoclax, teglicar significantly reduced IC50 of venetoclax by 5.33 and 1.7 folds in RPMI 8226 and U266B1 respectively. In addition, single agent and combination treatment were associated with a significant increase in apoptosis in both cell lines. However, the combination therapy had no significant effect on reactive oxygen species (ROS) levels in either cell lines. Our results suggest that the combination of teglicar and venetoclax holds promise in multiple myeloma through induction of apoptosis. This study sheds light on the potential therapeutic implications of targeting FAO, specifically through CPT1 inhibition, in conjunction with apoptosis inducers for enhanced anticancer effects in multiple myeloma

Medications Associated with Geriatric Syndromes and Prescribing Patterns: The Impact of Excessive Polypharmacy in Older Adult Patients

Ahmad Al-Azayzih,1 Walid Al-Qerem,2 Sayer Al-Azzam,1 Karem H Alzoubi,3,4 Feras Jirjees,3 Khalid Al-Kubaisi,3 Zelal Kharaba,3,5 Suhaib Muflih,1 Roaa J Kanaan,1 Ayah H Abandeh1 1Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, 22110, Jordan; 2Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman, 11733, Jordan; 3Department of Pharmacy Practice and Pharmacotherapeutics, College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates; 4Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, 22110, Jordan; 5Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, NE2 4HH, UKCorrespondence: Ahmad Al-Azayzih, Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, 22110, Jordan, Email [email protected] of the Study: To assess the prescribing patterns of medications associated with geriatric syndromes (MAGS) in older adult patients with multiple comorbidities and to identify factors that may increase the risk of MAGS prescribing in the same population.Methodology: This study involved a retrospective analysis of the electronic medical records of older adult patients (≥ 65 years) who visited outpatient clinics at King Abdullah University Hospital (KAUH) in Jordan between January 1, 2019, and June 1, 2024. The collected data included patient demographics, medical history, and medications, focusing on those associated with geriatric syndromes. Descriptive and logistic regression statistical analyses were performed using SPSS with the significance level set at p < 0.05.Results: The study included 1087 older adult patients (52.7% female), with a median age of 71 years. The common conditions existed were peptic ulcer disease (57.1%), hypertension (54.65%), and uncomplicated diabetes (50%). Polypharmacy was presented in 94.8% of total patients number, with 41.6% experiencing excessive polypharmacy. Antihypertensives (78.4%), non-opioid analgesics (56.5%), and antidiabetics (51.8%) were the most frequently prescribed MAGS, which frequently resulted in falls (96%), urinary incontinence (87.6%), and depression (87.3%). Patients with excessive polypharmacy had significantly higher MAGS scores than those with moderate or mild polypharmacy (95% CI: − 2.230 to − 1.770 and − 3.322 to − 2.678, respectively, P < 0.001).Conclusion: The findings demonstrate a high prevalence of excessive polypharmacy among older adult patients, significantly contributing to the elevated prescription level of medications associated with geriatric syndrome occurrence, particularly falls, urinary incontinence, and depression.Keywords: polypharmacy, geriatric syndromes, older adult, excessive polypharmacy, medications, elderl

Exploring public perception and utilization of medication home delivery services in the United Arab Emirates: a cross-sectional study

\ua9 The Author(s) 2024.Introduction: The Medication Home Delivery (MHD) service from community pharmacies involves the safe and efficient delivery of pharmaceuticals (prescription and non-prescription medications), and health products directly to the patient’s/consumer’s home. There are several issues encountered by the users of the MHD service that have an impact on their satisfaction with the service. The study aimed to assess the public’s perceptions of the MHD service in the United Arab Emirates (UAE), their willingness to utilize it, and the practical use of the service. Method: A cross-sectional exploratory study was conducted in the UAE using a validated online survey. The inclusion criteria were adults residing in the UAE. Statistical analysis was performed to identify the association between the variables, the service use, and the level of service efficiency. Results: A total of 556 participants filled out the survey, with 69.4% of them using the service. The majority of participants were females (75.9%) and aged less than 40 years old (71.6%). Three variables showed a statistically significant association with the use of the MHD service (P &lt; 0.05): the participant’s educational level, their medical/health background, and the frequency of visits to community pharmacies. The most common issues raised were receiving the wrong order, delay in delivery, and paying delivery fees. Most participants agreed that the MHD service reduces the risk of exposure during pandemics, serves the elderly, serves disabled people, makes it more comfortable for parents with children at home, and reduces overcrowding in health facilities, as well as the MHD service making pharmacy services more efficient. Conclusion: The study indicated positive perceptions among the public in the UAE towards the MHD service. However, there was a concern that this service may diminish the communication between pharmacists and patients, which potentially minimizes the amount of information received by patients regarding their treatments

Anticholinergic burden risk and prevalence of medications carrying anticholinergic properties in elderly cancer patients in Jordan

Background: Geriatric cancer patients are susceptible to adverse drug events due to the complexity of their chemotherapy regimens and collateral treatments for their comorbid conditions. Prescribing medications with anticholinergic burden characteristics can complicate their condition, leading to negative impacts on their health outcomes and quality of life, including an increase in adverse drug event frequency, physical and cognitive impairments. Objective: This study aims to examine the prevalence of anticholinergic prescribing and identify the cumulative anticholinergic load risk associated with drugs prescribed to elderly cancer patients. Also, to identify the predictors that might lead to raised anticholinergic burden in these patients. Methodology: This retrospective cross-sectional study included elderly patients (age ≥ 65) diagnosed with cancer and admitted to the adult oncology unit at King Abdullah University Hospital (KAUH) in Jordan during the period between (January 1st, 2019, and January 1st, 2022). The medication charts of 420 patients were evaluated for study outcomes. Results: Of the total subjects, females represented 49.3%, and the average age was 72.95 (SD = 7.33). A total of 354 (84.3%) patients were prescribed at least one drug carrying anticholinergic burden properties. Median for anticholinergic medications was 3 (IQR = 4). Our study found that 194 (46.2%) patients were at a high risk of adverse events associated with anticholinergic load (cumulative score ≥ 3). Metoclopramide, furosemide, and tramadol were the most frequently prescribed drugs with anticholinergic properties. Alimentary tract drugs with anticholinergic action were the most commonly encountered items in our study population. Conclusion: Our study revealed a significantly high prevalence of anticholinergic prescribing among elderly cancer patients. Nearly half of the patients were at high risk of developing serious effects related to anticholinergic activity from the drugs administered. Polypharmacy was strongly associated with increased anticholinergic burden score. Evidence-based recommendations utilizing prescribing strategies for safer alternatives and deprescribing of inappropriate medications could reduce such inappropriate prescribing

Inappropriate Medications Use among Elderly Cancer Patients According to Beer’s Criteria

Background: The global population of elderly has substantially increased in recent years due to heightened life expectancy and improved survival rates for numerous diseases, including cancer. Cancer treatment often entails complex regimens involving multiple medications. Additionally, advancing age is associated with a higher prevalence of co-morbidities, rendering older individuals more susceptible to inappropriate medications use and adverse drug events. Objective: We aimed in our study to examine the extent of Potentially Inappropriate Medications (PIMs) prescribing and factors associated with more PIMs instances in elderly cancer patients. Methods: The data of this study was evaluated utilizing medical records of included study subjects and was conducted over more than 3 years period (January 1, 2019 to January 31, 2022) at King Abdullah University Hospital, Al Ramtha, Jordan. Beer’s criteria 2019 was used to evaluate and identify the potentially inappropriate drugs prescribed and used among elderly cancer patients. Results: A total number of 250 geriatric cancer patients were included in this study. The mean age of the patients was 73.4 years. Males represented 50.4% of the total patients (n=126). The average number of medications reported was 10.7 medications. Eighty three percent (n=203) of patients had polypharmacy (prescribed at least five medications or more), A total of 179 medications were considered inappropriate according to the 2019 updated BEERS criteria and 71.6% of patients (n=179) received at least one PIM. The most common classes of PIMs were gastrointestinal medications (e.g., metoclopramide). Conclusion:According to this study, the incidence of PIMs in geriatric oncology practice is concerning, and extra consideration should be given to reduce any risks associated with this kind of prescribing in elderly cancer patients. Polypharmacy was found to be a major predictor of PIM prescription in this researc

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

Ahmad Al-Azayzih,1 Walid Al-Qerem,2 Sayer Al-Azzam,1 Suhaib Muflih,1 Belal A Al-Husein,1 Zelal Kharaba,3,4 Roaa J Kanaan,1 Dania Rahhal1 1Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan; 2Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman, Jordan; 3College of Pharmacy, AL Ain University, Abu Dhabi, United Arab Emirates; 4Honorary Associate Lecturer, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UKCorrespondence: Ahmad Al-Azayzih, Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan, Email [email protected]: 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.Keywords: torsade de pointes, QTc interval, critically ill patients, Jordan, intensive care uni

Pharmacy Students Perceptions of Their Distance Online Learning Experience During the COVID-19 Pandemic: A Cross-Sectional Survey Study

Introduction: The COVID-19 pandemic imposed dramatic changes on educational practices worldwide. Many universities and schools have moved into the delivery of their courses and educational programs utilizing fully electronic online modes. This study aims to evaluate the pharmacy student distance online learning experience during the COVID-19 pandemic. Methods: A cross-sectional survey was utilized where a 3-domain survey questionnaire focused on preparedness, attitude and barriers was distributed to students at the time of conclusion of the semester. Each domain consists of multiple questions that made up a score that reflects their preparedness, attitude as well as barriers relevant to distance online learning experience. The survey was voluntarily, and all data were collected and recorded via google forms with maintaining anonymity. Results: The response rate was about 75% (n = 309). The results’ analysis revealed no gender differences in any of these domains. However, there were some variable responses among different educational levels. The average preparedness score was 32.8 ± 7.2 (Max 45), the average attitude score was 66.8 ± 16.6 (Max 105), and the average barrier score was 43.6 ± 12.0 (Max 75). There was statistical significance difference in both preparedness score and attitude scores between different professional years ( P-value &lt;.05). However, there was no difference in barrier scores among all professional years. The results indicated that about 61.4% of the students agreed on that college of pharmacy was well-prepared and ready for the online education during the emerging COVID-19 pandemic with complete transition into online education. The results also indicated that 49.2% of the students showed positive attitude toward the provided online learning. The results indicated that about 34% of the students identify some barriers toward the provided online learning. Finally, there were strong association between the need for training on how to receive online courses and preparedness and barriers scores. Discussion and conclusion: E-learning experience pose challenges and presents opportunities during emergency situations. The need for training for students and faculty was highly associated with the preparedness and barriers domains rather than the infrastructure or computer literacy, so the school can improve their experience by addressing these needs. </jats:sec

Artificial intelligence in pharmacy practice: Attitude and willingness of the community pharmacists and the barriers for its implementation

Background: Artificial intelligence (AI) is the capacity of machines to perform tasks that ordinarily require human intelligence. AI can be utilized in various pharmaceutical applications with less time and cost. Objectives: To evaluate community pharmacists’ willingness and attitudes towards the adoption of AI technology at pharmacy settings, and the barriers that hinder AI implementation. Methods: This cross-sectional study was conducted among community pharmacists in Jordan using an online-based questionnaire. In addition to socio-demographics, the survey assessed pharmacists’ willingness, attitudes, and barriers to AI adoption in pharmacy. Binary logistic regression was conducted to find the variables that are independently associated with willingness and attitude towards AI implementation. Results: The present study enrolled 401 pharmacist participants. The median age was 30 (29–33) years. Most of the pharmacists were females (66.6%), had bachelor’s degree of pharmacy (56.1%), had low-income (54.6%), and had one to five years of experience (35.9%). The pharmacists showed good willingness and attitude towards AI implementation at pharmacy (n = 401). The most common barriers to AI were lack of AI-related software and hardware (79.2%), the need for human supervision (76.4%), and the high running cost of AI (74.6%). Longer weekly working hours (attitude: OR = 1.072, 95% C.I (1.040–1.104), P < 0.001, willingness: OR = 1.069, 95% Cl. 1.039–1.009, P-value = 0.011), and higher knowledge of AI applications (attitude: OR = 1.697, 95%Cl (1.327–2.170), willingness: OR = 1.790, 95%Cl. (1.396–2.297), P-value < 0.001 for both) were significantly associated with better willingness and attitude towards AI, whereas greater years of experience (OR = 20.859, 95% Cl (5.241–83.017), P-value < 0.001) were associated with higher willingness. In contrast, pharmacists with high income (OR = 0.382, 95% Cl. (0.183–0.795), P-value = 0.010), and those with<10 visitors (OR = 0.172, 95% Cl. (0.035–0.838), P-value = 0.029) or 31–50 visitors daily (OR = 0.392, 95% Cl. (0.162–0.944), P-value = 0.037) had less willingness to adopt AI. Conclusions: Despite the pharmacists' positive willingness and attitudes toward AI, several barriers were identified, highlighting the importance of providing educational and training programs to improve pharmacists' knowledge of AI, as well as ensuring adequate funding support to overcome the issue of AI high operating costs

Pronerve Growth Factor Induces Angiogenesis via Activation of TrkA: Possible Role in Proliferative Diabetic Retinopathy

Proliferative diabetic retinopathy (PDR) is the leading cause of blindness in working age Americans. We demonstrated that diabetes disturbs the homeostasis of nerve growth factor (NGF) resulting in accumulation of its precursor proNGF. Increases in proNGF were positively correlated with progression of diabetic retinopathy, having the highest level in ocular fluids from PDR patients compared to nondiabetic patients. Here, we attempted to evaluate the contribution and the possible mechanism of proNGF to PDR. The angiogenic response of aqueous humor samples from PDR patients was examined in human retinal endothelial cells in the presence or absence of anti-proNGF antibody. Additional cultures were treated with mutant-proNGF in the presence of specific pharmacological inhibitors of TrkA and p75NTR receptors. PDR-aqueous humor samples exerted significant angiogenic response including cell proliferation, migration, and alignment into tube-like structures. These effects were significantly reduced by anti-proNGF antibody but not by IgG. Treatment of retinal endothelial cells with mutant-proNGF activated phosphorylation of TrkA and p38MAPK; however, it did not alter p75NTR expression. Inhibition of TrkA but not p75NTR significantly reduced mutant-proNGF-induced cell proliferation, cell migration, and tube formation. Taken together, these results provide evidence that proNGF can contribute to PDR at least in part via activation of TrkA