Search

Background: Pharmaceutical excipients have been shown to influence drug disposition through modulating transport protein. Objectives: This study assessed the effect of single dose administration of parabens on the pharmacokinetics (PK) of digoxin, a probe substrate of p-glycoprotein (p-gp), in vivo. Also, the effect of multiple dosing of parabens on p-gp expression was examined. Methods: Rats were randomized into four groups that received either the vehicle, 25 mg/ kg verapamil, 100 mg/ kg isobutyl paraben, or 100 mg/ kg 2-ethyl hexyl paraben, which was followed by giving 0.2 mg/ kg digoxin via oral gavage. Blood samples were collected at different time points, digoxin concentration was measured using LC/MS-MS, and digoxin PK parameters were estimated. Another set of rats received multiple doses of parabens for 14 days, followed by measuring intestinal and hepatic mRNA expression of p-gp using qRT-PCR. Results: Single dose administration of verapamil significantly increased Cmax (by 60.4 %) and AUC0-t (by 61.7 %) of digoxin compared to the control group, while the PK parameters of digoxin in rats exposed to parabens were not significantly different from the control. Consistently, the mRNA expression of p-gp in the intestine and liver was not affected by parabens treatment. Conclusions: The lack of isobutylparaben and 2-ethylhexyl paraben effect on p-gp may suggest the insignificant interaction of parabens with p-gp drug substrates, which could be considered for safety when designing pharmaceutical formulations.

Ribociclib is a newly approved orally administered drug for breast cancer. This study aimed to prepare, characterize, and evaluate hybrid lipid–polymer nanoparticles (PLNs) of ribociclib to enhance its in vitro dissolution rate, pharmacokinetics, and anticancer efficacy. Ribociclib-loaded PLNs were prepared by solvent evaporation using the Box–Behnken design to optimize formulation variables. Particle size, entrapment efficiency, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), in vitro release cytotoxicity, molecular modeling, and pharmacokinetic studies were examined. The ribociclib-loaded PLN (formula 1, F1) was optimized in terms of particle size (266.9 ± 4.61 nm) and encapsulation efficiency (59.1 ± 2.57 mg/mL). DSC and thermogravimetric characterization showed the absence of a crystalline structure in the prepared PLNs, confirmed by FTIR, and showed no interactions between the components and the drug. AFM showed well-dispersed heterogeneously shaped nanoparticles. The in vitro release profile exhibited significant results for the optimized formula, reaching 100% at 600 and 90 min at pH 6.8 and 1.2, respectively. The low IC50 obtained by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay suggests that optimized PLN might serve as an effective delivery vehicle for cancer treatment, especially breast and lung cancer. Molecular modeling revealed several hydrogen bonds. A pharmacokinetic study in rats showed that the ribociclib formula had a 6.5-fold increase in maximum concentration (Cmax) and a 5.6-fold increase in area under the curve (AUC). Regarding the everted intestinal sac absorption, formula 1 increased ribociclib penetration relative to the physical combination and pure medication. In conclusion, optimized PLNs with enhanced physicochemical and cytotoxic properties and improved pharmacokinetic parameters were successfully prepared.

Mushroom poisoning is a worldwide public health problem that may cause serious toxic consequences on renal functions. The study aimed to evaluate the acute toxicity (24 h) of orellanine (OR) from Cortinarius orellanus in rat kidney and the ameliorative effect of parsley ethanolic extract. Twelve adult male Wistar rats were used to determine intraperitoneal (ip) median lethal dose (LD

Anemia is prevalent in hemodialysis (HD) patients. Data about factors associated with medication non-adherence in anemic HD patients is limited. This study examined determinants of medication non-adherence and its association with achievement of therapeutic goals of anemia measures among HD patients.A cross-sectional study was conducted among a representative group of HD patients in Jordan. Medication adherence was assessed using Morisky Green Levine Medication Adherence Scale (MGL). Other utilized instruments were modified Charlson Comorbidity Index (mCCI), general Health-Related Quality of Life (HRQoL) EQ-5D-5 L, and Hospital Anxiety and Depression Scale (HADS). Pharmacy claim data during the years of (2016-2017) were also retrieved from patients' medical records. Logistic regression was conducted to identify factors associated with medication non-adherence and achieving therapeutic goals of anemia therapy.More than two-thirds of the participants (69.1%) were found non-adherent and the mean score of MGL scale was 2.4 ± 1.4. The non-adherence rate measured using refill data (69.6%) was comparable to that observed using self-reported MGL instrument. Education level of college or over was significantly associated with lower odds of non-adherence (OR = 0.365, p = 0.036), while complaining of a headache was associated with 2.5-fold risk of medication non-adherence (OR = 2.5, p = 0.017). A trend toward better achievement of iron indices therapeutic goals was observed with improved adherence measured using refill data. Multiple factors such as improved knowledge about prescribed medications was significantly associated with achieving anemia therapeutic goals (p 0.05).The findings suggest poor medication adherence among HD patients with anemia. Future interventions by health-care providers should target modifiable factors to improve medication adherence and, hence, health outcomes among HD patients with anemia.

Background Understanding health care professionals' perceptions towards a Computerised Decision Support System (CDSS) may provide a platform for the determinants of successful adoption and implementation of CDSS. Therefore, this study examines health care professionals' perceptions of barriers and facilitators to adopting a CDSS for antibiotic prescribing in Jordanian hospitals. Methods This cross-sectional study was conducted among healthcare professionals in Jordan's two tertiary and teaching hospitals (n = 254). The survey was adapted from a previous study and comprised demographic items and scales to measure perceptions of healthcare professionals towards the barriers and facilitators to the adoption of CDSS for antibiotic prescribing were developed. In addition, Uni and multivariate logistic regression analyses were applied to screen for factors affecting participants' awareness of using electronic prescribing and electronic health record systems in AMS. Results The majority (n = 84, 72.4%) were aware that electronic prescribing and electronic health record systems could be used to facilitate antibiotic use prescribing. The essential facilitator made CDSS available in a portable format (n = 224, 88.2%). While, insufficient training to use CDSS was the most significant barrier (n = 175, 68.9%). The female providers showed significantly lower awareness (P = 0.006) and the nurses significantly higher awareness (P = 0.041) about using electronic prescribing and electronic health record systems. Conclusion This study examined health care professionals' perceptions towards adopting CDSS in AMS. Results provide insight into the perceived barriers and facilitators to adopting CDSS in AMS.

Suhaib Muflih,1 Osama Y Alshogran,1 Sayer Al-Azzam,1 Ghaith Al-Taani,2 Yousef S Khader3 1Department of Clinical Pharmacy, Jordan University of Science and Technology, Irbid, 22110, Jordan; 2Department of Pharmacy Practice, Yarmouk University, Irbid, Jordan; 3Department of Public Health, Jordan University of Science and Technology, Irbid, 22110, JordanCorrespondence: Suhaib MuflihFaculty of Pharmacy, Jordan University of Science and Technology, Irbid, 22110, JordanTel +962-79-7868603Email smmuflih@just.edu.joIntroduction: Pharmacogenetic testing (PGx) is a diagnostic technique used by physicians to determine the possible reactions of patients to drug treatment on the basis of their genetic makeup. The aim of this study was to determine the impact of physicians’ awareness, attitudes, and sociodemographics on the adoption of point-of-care (POC) PGx testing as a diagnostic method, as well as the impact of their knowledge, attitudes, and sociodemographics on its adoption.Methods: A cross-sectional survey of 200 physicians and medical trainees working at the Clinics of King Abdullah University Hospital in Jordan was performed. Data on sociodemographics, knowledge and attitudes concerning PGx testing, genetic information sources, and barriers to POC-PGx testing adoption were gathered.Results: Participants’ perceived knowledge of the role of PGx testing in therapeutic decision-making was rated as “Excellent” (1.9%), “Very Good” (19.4%), “Good” (34.4%), “Fair” (32.5%), and “Poor” (11.9%). Physicians’ actual knowledge of PGx testing was adequate (mean=3.56 out of 7, SD=1.2), but their attitudes were generally favorable (mean=3.64 out of 5.00, SD=0.52). According to Rogers’ theory, many variables (eg, perceived need, relative advantage, compatibility) had a significant impact on physicians’ willingness to endorse POC-PGx testing.Discussion: The majority of physicians stated that they were unaware of PGx testing. Physicians’ perceived knowledge of POC-PGx testing, however, was higher than those who participated in other studies. Participants were optimistic about the future benefits of PGx testing in prescribing effective medications and reducing potential side effects, which were consistent with previous studies. Physicians’ willingness to accept and implement POC-PGx testing was hampered by a lack of PGx expertise, as well as concerns about patient confidentiality, employability, and insurability. More training and genetic courses are needed, according to the majority of participants.Keywords: pharmacogenetics, physicians, knowledge, attitudes, point-of-care, Rogers theory

This study reports new solubility and physicochemical data for ribociclib (RCB) in water and ten organic solvents including “methanol (MeOH), ethanol (EtOH), isopropyl alcohol (IPA), n-butanol (n-BuOH), propylene glycol (PG), polyethylene glycol-400 (PEG-400), acetone, ethyl acetate (EA), Transcutol-HP (THP), and dimethyl sulfoxide (DMSO)” at 293.2–313.2 K and 101.1 kPa. The obtained data are useful for the industrial applications of RCB. The solubility of RCB was measured and regressed using “van’t Hoff, Buchowski-Ksiazczak λh, the modified Apelblat, and Jouyban models.” The overall deviations of −2 in PEG-400 at 313.2 K, however, the lowest one was in the water. The RCB solubility increased with temperature and the order followed in the water and ten different organic solvents was PEG-400 (2.66 × 10−2) > THP (1.00 × 10−2) > PG (5.39 × 10−3) > DMSO (5.00 × 10−3) > n-BuOH (3.23 × 10−3) > acetone (3.11 × 10−3) > IPA (1.58 × 10−3) > EA (1.41 × 10−3) > EtOH (1.37 × 10−3) > MeOH (8.10 × 10−4) > water (2.38 × 10−5) at 313.2 K. The maximum solute-solvent interactions were found in RCB-PEG-400 in comparison with other combination of RCB and solvents. “Apparent thermodynamic analysis” indicated an “endothermic and entropy-driven dissolution” of RCB in water and ten organic solvents. Based on all these data and observations, PEG-400 can be used as the best co-solvent for RCB solubilization.

Combined antioxidants effect for prevention of contrast-induced nephropathy (CIN) remains unclear. This study assessed the potential protective effects of coenzyme Q10 (CoQ10) alone or combined with N-acetyl cysteine (NAC) or atorvastatin against CIN in diabetic rats. Animals were randomly divided into five groups, including control and four disease groups with CIN and diabetes. Group 2 included diabetic rats with CIN. Groups 3-5 included diabetic rats that received CoQ10, CoQ10 and NAC, or CoQ10 and atorvastatin, respectively, before CIN induction. Serum, urine, and tissue were collected to evaluate renal protective effects of tested agents. Renal biomarkers, oxidative stress, and histopathological alterations were investigated. Rats with CIN showed significant renal impairment as revealed by the deleterious effects on kidney function and histology. While induction of CIN did not affect the renal levels of catalase, glutathione peroxidase (GPx), and thiobarbituric acid reactive substances, pretreatment of animals with CoQ10/NAC showed significant increase in GPx and catalase levels versus controls. Lastly, pretreatment with CoQ10/atorvastatin showed regenerative effect on distal tubules with mild kidney histology alterations relative to CIN rats. The combined use of CoQ10/atorvastatin could be a potential strategy to prevent CIN. However, future studies are warranted to test different combinations for longer prophylactic periods.

This study aimed to describe clinical outcomes and medical expenditures associated with COVID-19 admissions. In addition, this study aimed to investigate the impact of patients' characteristics and baseline comorbidities on intensive care unit (ICU) admission, mortality, and medical expenditures for hospitalized patients with COVID-19.This retrospective cohort study included all hospitalized patients with confirmed COVID-19 in Prince Hamza Hospital and King Abdullah University Hospital, during the period from March 2020 to June 2021. Medical records and pharmacy data were followed and reviewed throughout their admissions. The ICU admission, inpatient mortality, hospital length of stay, and inpatient charges were described. Predictors of ICU admission and inpatient charges were evaluated.A total of 7694 COVID-19 hospital admissions were included. Approximately 1189 patients (15.5%) were admitted to ICU and 21.4% died in the hospital. The fatality rate among those admitted to ICU was 82.6% compared with 10.2% for non-ICU admitted patients. The average admission charge and charge per admission day were 1598.2 and 200.2 Jordanian dinar, respectively, and both charges were higher in ICU admitted patients than non-ICU admitted patients. Being older in age, smoker or ex-smoker, and having chronic diseases were all significantly associated with a higher likelihood of ICU admission and mortality among admitted patients.ICU admission in patients with COVID-19 is associated with poor clinical outcomes and substantial medical expenditures and is more likely among older adults, smokers, and those with chronic diseases.

Psychiatric illness is prevalent among hemodialysis (HD) patients. This study compared the assessment of anxiety and depressive symptoms among HD patients using two self-administered scales; hospital anxiety and depression scale (HADS) and brief symptom inventory (BSI).A cross-sectional study was conducted among a convenience sample of HD patients (n = 352) from different dialysis centers in Jordan. Patients were interviewed in dialysis units, and demographics, clinical status, disease, and dialysis history data were collected. Symptoms of anxiety (HADS-A ≥ 8 and BSI-A ≥ 0.82) and depression (HADS-D ≥ 8 and BSI-D ≥ 0.82) were also measured.The mean age of participants was 52.2 ± 15.6 years. The majority had been receiving HD three times daily and for2 years. A significant moderate-strong correlation was observed between HADS-A and BSI-A (r = 0.753, p 0.0001) as well as HADS-D and BSI-D (r = 0.588, p 0.0001). Anxiety prevalence was 43.7 % using HADS-A ≥ 8 and 80.7 % using BSI-A ≥ 0.82, while depression prevalence was 53.1 % using HADS-D ≥ 8 and 51.7 % using BSI-D ≥ 0.82. When HADS was used as a standard, the operating characteristics reveal that a higher cut-off for BSI-A is recommended (≥1.58) for better anxiety screening.Specific and suitable cut-off points need to be further explored and validated for HADS and BSI scales among patients undergoing dialysis.

This study investigated the clinical characteristics and symptomatology of ESRD patients in Jordan taking a multidimensional approach. This was a cross-sectional study that included a cohort of 620 patients undergoing maintenance hemodialysis (HD). Data were retrieved via patient survey administration and electronic health records. A modified version of the Charlson Comorbidity index (CCI) was utilized to assess comorbidity. Symptoms were assessed using the validated Arabic version of the CKD Symptom Burden Index (CKD-SBI). The mean (± SD) age of participants was 50.9 ± 16.1 years, with the 59.8% being males. Diabetes was the leading cause of kidney disease among patients (29.2%), followed by hypertension (20.7%) and medication use (8.6%). Common comorbidities included hypertension (72.4%), diabetes (38.4%), and cardiovascular disease (18.7%). Patients experienced 13 CKD-related symptoms on average, with a total symptom burden score of 29.6. Muscle strain was the most common symptom (62.6%), followed by itchiness (59.7%), nervousness (57.7%), and anxiety (57.7%). Charlson comorbidity index (CCI) [β = 0.88, 95% CI (0.34–1.41)], male gender [β = − 5.59; 95% CI (− 8.34 to − 2.85)], higher educational level [β = − 3.38; 95% CI (− 6.39 to − 0.37)], and number of dialysis sessions/week (β = 6.22, 95% CI 3.37–9.07) were independent predictors of total symptom burden. Similarly, these factors predicted symptom troublesomeness, intensity, and recurrence. A holistic clinical picture of ESRD that includes multidimensional symptom assessment is warranted for better disease management and resource allocation. Our paper identifies key characteristic of this population and factors contributing to total symptom burden.

This study aimed to explore healthcare providers' (HCP) stigmatization from patients during the COVID-19 outbreak in Jordan.A cross-sectional design was used. Data collection was conducted between May and July 2021. The research questionnaire included demographic information about participants and multiple statements that reflect stigma of participants toward HCPs. Regression analysis was conducted to assess the association between stigma and explanatory variables.A total of 777 surveys were included in the study. Many people show high stigma toward HCPs during COVID-19 pandemic. Various factors including hearing news all time (p.001), having children (p.024), and smoking (p.001) were significant in prediction stigma toward HCPs.This one of few studies conducted in Jordan regarding the stigma toward HCP from other people with chronic diseases. Our study found that many people showed some stigma toward HCP during COVID-19. Stigmatization of HCP related to a pandemic is a lesson most people have not learned. It is not enough to cheer HCPs. A clear, sensible public education campaign about the public's risks by interacting with HCP is necessary.

Implementing interprofessional education (IPE) in health professions curricula requires considerations of students’ attitudes and readiness. Interventional studies that assess students’ perceptions about IPE are needed. As IPE is an emerging concept in Jordan, our study aimed at exploring the attitudes of health profession students about IPE and collaborative practice before and after implementing an IPE activity. Students completed the validated Interprofessional Attitudes Scale (IPAS) before and after completing a 3-hour interprofessional activity. Students’ attitudes toward IPE were compared using the subscales and total IPAS scores. A total of 41 health profession students attending the professional health programs of Doctor of Pharmacy, Medicine, Nursing, Nutrition, or Pharmacy completed IPAS before and after conducting the interprofessional activity. Students reported positive attitudes toward IPE prior to the activity. Significant increases were observed in IPAS scores from pre- (median [interquartile range: IQR] score = 4.19 [0.61]) to post-activity (median [IQR] = 4.48 [0.65]), and in its subscales (teamwork, roles and responsibilities, diversity and ethics, and community-centeredness). Students’ experience with the IPE activity was positive and optimistic. The findings revealed for the first time the perception and readiness of health profession students toward IPE and collaborative practice in Jordan. This readiness can help draw a path for strategic integration of IPE in health profession curricula.

OBJECTIVE This study evaluated the impact of various factors on age at natural menopause as well as psychiatric symptoms including anxiety and depression among postmenopausal women in Jordan. METHODS A cross-sectional study was conducted and included females with natural menopause (n = 450). A structured interview-based questionnaire was used to collect data about subjects' sociodemographics, health, reproductive and environmental factors. Hospital anxiety and depression scale (HADS) was used to assess psychiatric symptoms. Factors associated with age at natural menopause, depression, or anxiety were identified. RESULTS The mean age at natural menopause was 49.5 ± 4.8 years. Mothers' age at menopause, the regularity of cycles, age at last pregnancy and diabetes were significant positive predictors of age at menopause (p

Background: Chronic Kidney Disease (CKD) is a prevalent worldwide health problem. Patients with CKD are more prone to developing cardiovascular complications such as atrial fibrillation and stroke. This warrants the use of oral anticoagulants, such as warfarin, in this population. While the efficacy and safety of warfarin in this setting remain controversial, a growing body of evidence emphasizes that warfarin use in CKD can be problematic. This review discusses 1) warfarin use, dosing and outcomes in CKD patients; and 2) possible pharmacokinetic mechanisms for altered warfarin dosing and response in CKD. Methods: Structured search and review of literature articles evaluating warfarin dosing and outcomes in CKD. Data and information about warfarin metabolism, transport, and pharmacokinetics in CKD were also analyzed and summarized. Results: The literature data suggest that changes in warfarin pharmacokinetics such as protein binding, nonrenal clearance, the disposition of warfarin metabolites may partially contribute to altered warfarin dosing and response in CKD. Conclusion: Although the evidence to support warfarin use in advanced CKD is still unclear, this synthesis of previous findings may help in improving optimized warfarin therapy in CKD settings.

Background Informed consent is one of the primary standards of ethical clinical research. This study assessed the quality of the informed consent forms (ICF) utilized in medical research conducted in Sudan and Jordan. Subjects and methods A total of 435 studies that were performed at health sciences schools in Jordan and Sudan were initially screened for the presence of ICF. Of these, 189 studies were reviewed for the major components of ICF using a standard checklist. Results The majority of the reviewed ICFs did not achieve the full standards of the universal guidelines for the informed consent structure. The following elements were described in >50% of consent forms reviewed from both countries: study title, objectives, research investigators, description of study procedure, and confidentiality. Other essential elements such as duration of the subject's participation, risks/benefits, compensation, voluntary participation, and contact information were poorly described. Conclusion The major elements of ICFs were not adequately described in medical research studies from Jordan and Sudan. Improved understanding of major elements of ICF among researchers in the examined countries is necessary. Clear and informative consent template can be very valuable in this perspective.

Objective: This study aimed to 1) develop and validate a simple, accurate and reproducible high-performance liquid chromatography–tandem mass spectrometry method for determination and quantification of naltrexone and its reduced metabolite (6-beta naltrexol); 2) assess the effect of uremic toxins on metabolic reduction. Methods: Sample preparation was conducted through liquid-liquid extraction of analytes spiked in 10 mM Tris-HCl incubation buffer (pH 7.4) using methyl tert-butyl ether. The chromatographic separation of analytes was achieved using Inert Sustain C18 (2.1 x 50 mm, 5 μm) analytical column under isocratic elution of solvent A (water containing 0.1% formic acid) and solvent B (methanol containing 0.1% formic acid) over a run time of 5 min. The analytes were detected by multiple reaction monitoring with electrospray ionization in the positive mode. Results: Excellent linearity was observed for all analytes over the concentration ranges of 100-8,000 ng/mL for naltrexone and 10-800 ng/mL for 6-beta naltrexol. The intra- and inter-day accuracy and precision for analytes were within ±15.0%. The method is accurate and precise and novel in its application to in vitro experiments assessing the effect of uremic toxins on metabolic reduction of naltrexone, which showed that indoxyl sulfate (100 μM) is a significant inhibitor of naltrexone reduction. Conclusion: The developed method is reproducible and accurate and well suited for conducting enzyme kinetic studies assessing metabolic reduction. Key words: Naltrexone, 6-beta naltrexol, Reduction, LC-MS, Enzyme kinetics, Uremic toxins.

Purpose: This study aimed to identify factors correlating with hypertensive patients' compliance with lifestyle recommendations in north of Jordan. Patients and methods: A cross-sectional survey and face-to-face interview methods were used to collect the data from 1000 adult Jordanian hypertensive patients (>18 years old). A questionnaire was developed based on previous literature and professional consultation. Results: Only 23% of the patients were fully compliant with healthy lifestyle behaviors. About 95% were knowledgeable on hypertension and 86% had positive beliefs about the management protocols of their disease. Gender, physician counseling on a healthy lifestyle, patients' beliefs about hypertension management, and their knowledge on hypertension and its management have an independent effect on compliance with lifestyle recommendations. Conclusion: Patients' compliance with lifestyle recommendations was low. Receiving counseling from physicians about healthy lifestyle and self-care; being informed about hypertension and its management; and having positive beliefs about managing this disease are significant predictors of patients' compliance with lifestyle recommendations.

Introduction Overactive bladder (OAB) is a prevalent syndrome that is associated with multiple urinary tract symptoms and could affect the patient's quality of life and well-being. Vitamin D is shown to be linked to OAB syndrome, which exacerbated by stress conditions. This study evaluated the relationship between vitamin D status, daily calcium intake and OAB, and the associated psychological symptoms. Methods The study included 55 patients with OAB and 129 healthy controls. Psychological symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS). Serum vitamin D was measured. Patients with OAB with low vitamin D level received orally vitamin D supplementation. Urinary symptoms, psychological symptoms, and quality of life were evaluated before and after vitamin D supplementation plus dairy products. Results Vitamin D deficiency was more prevalent in cases (80%) vs controls (34.9%). Depression (43.7% vs 20.2%) and anxiety (52.8% vs 10.9%) scores (HADS, ≥8) were also more frequent in cases vs controls, respectively. Some 85.5% of the patients' group had musculoskeletal pain vs 0.0% for the control. Depression was negatively correlated with daily calcium intake and positively with anxiety. Logistic regression analysis revealed that age, vitamin D, and anxiety scores were significant predictors of OAB. Vitamin D supplements with increased calcium intake had significant improvement in urinary symptoms, psychological distress, and quality of life. Conclusions Vitamin D supplements and improved calcium intake may improve urinary and psychological symptoms and quality of life among patients with OAB syndrome. Assessment for vitamin D status in patients with OAB may be warranted.

Background Warfarin use for stroke prevention in atrial fibrillation (AF) patients with chronic kidney disease is debated. Apixaban was shown to be safer than warfarin, with superior reduction in the risk of stroke, systemic embolism, mortality, and major bleeding irrespective of kidney function. Objectives To evaluate the cost-utility of apixaban compared with warfarin in AF patients at different levels of kidney function. Methods A Markov model was used to estimate the cost effectiveness of apixaban compared with warfarin in AF patients at three levels of kidney function: estimated glomerular filtration rate (eGFR) of more than 80 ml/min, 50 to 80 ml/min, and 50 ml/min or less. Event rates and associated utilities were obtained from previous literature. The model adopted the US health care system perspective, with hospitalization costs extracted from the Healthcare and Utilization Project. Treatment costs were obtained from official price lists. Univariate and probabilistic sensitivity analyses were performed to evaluate the robustness of results. Results Apixaban was a dominant treatment strategy compared with warfarin in AF patients with eGFR levels of 50 ml/min or less and 50 to 80 ml/min. In patients with an eGFR of more than 80 ml/min, apixaban was cost-effective compared with warfarin, costing $6307 per quality-adjusted life-year gained. Results were consistent assuming anticoagulant discontinuation after major bleeding events. Compared with dabigatran and rivaroxaban, apixaban was the only cost-effective anticoagulant strategy relative to warfarin in both mild and moderate renal impairment settings. Conclusions Apixaban is a favorably cost-effective alternative to warfarin in AF patients with normal kidney function and potentially cost-saving in those with renal impairment.

Background The outbreak of novel coronavirus (Covid-19) has a significant burden on global health and could be associated with significant mortality. Limited information exists about determinants of its fatality worldwide. Thus, this ecological study examined the association of various predictors with Covid-19 fatality. Methods International data bases of Covid-19 statistics and health metrics available primarily at WHO were reviewed to collect information for 113 countries. The dependent variable was Covid-19 case fatality rate. Independent variables were demographic, social, clinical, economic, heath care and child health factors. Results Case fatality rate of Covid-19 varies across countries with an average of 4.2 ± 3.8%, and about half of countries had fatality rate >3.2% (median). Significant relationships were observed between Covid-19 fatality rate and socio-economic, clinical, and health variables at the unadjusted regression analysis. At the multivariate adjusted model, percentage of population with age>60 years was positively associated with Covid-19 fatality (B = 0.032, p = 0.005), while Polio-3 immunization at 1-year old was inversely related (B = −0.057, p = 0.017). Conclusions This ecological investigation highlights the higher risk of death among elderly with Covid-19 pandemic and suggests that Polio-3 immunization coverage among 1-year-olds may be associated with better survival. Future research is warranted to validate these findings.

Background Estimating kidney function is essential to consider in drug dosing for renally eliminated drugs. It has been estimated that more than half of medications' adverse effects are caused by the inappropriate dosing. Limited data are available on drug dosing adjustment, particularly the antibiotics, among Jordanian patients with declined kidney function. Aim The aim of this study was to evaluate the extent of antibiotics' dose adjustment according to the recent guidelines of drugs' renal dose adjustment. Method The present study utilised data from a previous retrospective study, which recruited inpatients who were clinically stable and received IV antibiotics for more than 24 hours at King Abdullah University Hospital. Sociodemographic and clinical data were collected by referring to information technology departments at KAUH. The percentage of antibiotics which were inappropriately adjusted based on creatinine clearance was evaluated using Lexicomp-Clinical Drug information website. Results A total of 110 antibiotics were dispensed for 80 patients. Results showed that (36.25%) of patients were given antibiotics without renal dose adjustments based on their creatinine clearance. Urinary tract infections followed by respiratory tract infections were the most common among the study participants. The most commonly prescribed antibiotic was Imipenem/cilastatin (41.25%). Among antibiotics prescribed without renal dose adjustment, Imipenem/cilastatin was the most common and represented 62% of the cases while vancomycin was the least and represented only 3.45% of the non-renally adjusted doses. Conclusions The current study clearly demonstrates the lack of adherence to recent guidelines of renal dose adjustment for renally excreted antibiotics. Such findings shed the light on the necessity of considering antibiotics dose adjustment in patients with declined kidney function with the aim of ensuring medication safety and improve health outcomes.

This study assessed the possible association of serum brain-derived neurotrophic factor (BDNF) and interleukin-6 (IL-6) with depressive and anxiety symptoms in hemodialysis (HD) patients.An analytical cross-sectional study was conducted over 274 HD patients from March to October 2017. The Hospital Anxiety and Depression Scale (HADS) was utilized to evaluate depressive (HADS-D) and anxiety (HADS-A) symptoms. The HADS-D/A is a self-report instrument that has a maximum score of 21. Serum BDNF and IL-6 were measured using enzyme-linked immunosorbant assay (ELISA).Serum IL-6 was significantly higher in patients with depressive symptoms compared to normal (20.47 ± 4.27 pg/mL for HADS-D ≥11 versus 9.26 ± 1.59 pg/mL for HADS-D7, p = 0.014). Multivariable regression analysis revealed that IL-6, education level, hypertension, and dialysis duration were significant predictors of HADS-D. Also, gender, education level, hypertension, and the number of dialysis sessions/week were significant predictors of HADS-A. Significant positive correlation was shown between HADS-D and IL-6 (r = 0.1729, p = 0.004).Collectively, HD patients with depressive symptoms showed higher levels of IL-6, supporting previous findings that the circulating inflammatory mediator IL-6 can be used as a biomarker for prediction of depressive symptoms in HD patients. Further longitudinal or interventional studies are needed to further validate this association.

Aims The prevalence of metabolic syndrome (MetS) is increasing in several countries. The MetS is characterized by the occurrence of at least three of the following risk factors: decreased high-density lipoprotein cholesterol, increased blood pressure, raised fasting blood glucose, elevated triglycerides, and abdominal obesity. There is a growing evidence of the role of l -carnosine in improving lipid profile and enhancement of the antioxidant activity. However, the effects of l -carnosine on development of MetS are unknown. Main methods Male Wistar rats were randomly assigned to receive either; conventional diet (control), high-fat high-carbohydrate diet (HFHCD), l -carnosine and conventional diet (L-Car), or l -carnosine and high-fat high-carbohydrate diet (HFHCD and L-Car) for 16 weeks. Central obesity, systolic blood pressure, lipid profile, glucose hemostasis, levels of leptin and adiponectin were evaluated on week 16. Key findings Rats that received HFHCD for 16 weeks showed MetS phenotype such as central obesity, increased blood pressure and glucose, as well as an altered lipid profile (P l -Carnosine supplementation to MetS rats significantly reduced abdominal obesity, blood pressure and glucose, and normalized total cholesterol and low density lipoprotein cholesterol levels (P l -Carnosine (P > 0.05). Significance l -carnosine has beneficial effects on ameliorating the manifestations of MetS in rats.

Intracranial hemorrhage is a critical medical emergency. Nosocomial infections may promote worse outcomes in these vulnerable patients. This study investigated microbial features, predictors, and clinical outcomes of nosocomial infections among patients with multiple subtypes of intracranial hemorrhage.We conducted a retrospective cohort study of patients that were hospitalized with intracranial hemorrhage between January 2015 and October 2018, and divided them into two groups based on the development of nosocomial infection. Within the cohort of patients with nosocomial infections, microbiology and resistance patterns were established across multiple sites of infection. Moreover, consequences of nosocomial infection such as mortality and length of hospital stay were determined.A total of 233 cases were identified that met our inclusion and exclusion criteria out of which were 94 cases of nosocomial infection (40.3%) versus 139 cases with no nosocomial infection (59.7%). The most common infections were pneumonia, urinary tract infections, and bacteremia. Resistance accounted for 70.2% of cultures. Multivariable analysis revealed significant association of nosocomial infections with hypertension (OR: 2.62, 95% CI: 1.11-6.16, p = 0.027), hospital LOS (OR: 1.08, 95% CI: 1.05-1.12, p 0.001), levetiracetam (OR: 3.6, 95% CI: 1.41-0.922, p = 0.007), and GCS category (OR: 5.42, 95% CI: 1.67-17.55, p = 0.005 and OR: 7.63, 95% CI: 2.44-23.87, p 0.001 for moderate and severe, respectively). Patients with nosocomial infections witnessed a significant increase in the length of hospital stay (23 versus 8 hospital days, p 0.001). This finding was significant across most types of brain hemorrhage. Mortality was significantly associated with GCS category (OR: 10.1, 95% CI: 4-25.7, p 0.001) and percutaneous endoscopic gastrostomy tube insertion (OR: 19.6, 95% CI: 4.1-91, p 0.001).Collectively, these findings suggest that nosocomial infections are common among patients with intracranial hemorrhage and can be predictable by considering certain risk factors. Future studies are warranted to evaluate the efficacy of implementing infection control strategies or protocols on these patients to achieve better therapeutic outcomes.

Waterpipe smoke contains many toxic constituents that can alter drug pharmacokinetics. This study assessed the effect of waterpipe smoke exposure on the activity and expression of CYP450 enzymes in rats. Animals (n = 10/group) were exposed to either waterpipe smoke or side-stream cigarette smoke for 1 h/day (6 days/week) for 31 days, or fresh air (control). An intragastric cocktail solution containing three probe drugs, phenacetin, chlorzoxazone and testosterone was administered to assess the activity of CYP1A2, CYP2E1 and CYP3A, respectively. Serum concentrations were determined using LC-MS/MS and the pharmacokinetic parameters were calculated. The mRNA expression of hepatic enzymes was also quantified. Waterpipe and cigarette smoke exposure did not significantly alter the pharmacokinetics of phenacetin, chlorzoxazone and testosterone. For example, the clearance and drug exposure values were comparable among groups for all probe drugs. Additionally, there was no significant effect of waterpipe and cigarette smoke on mRNA expression of hepatic CYP1A2, CYP2E1 and CYP3A2. The results demonstrate that waterpipe smoke exposure had no effect on the functional expression of three key CYP450 isoforms in rats. Future research is required with longer exposure periods to waterpipe smoke. Such work serves to enhance current understanding of effect of waterpipe smoke exposure on pharmacokinetics.

Purpose: This study aimed to identify factors correlating with hypertensive patients’ compliance with lifestyle recommendations in north of Jordan. Patients and methods: A cross-sectional survey and face-to-face interview methods were used to collect the data from 1000 adult Jordanian hypertensive patients (>18 years old). A questionnaire was developed based on previous literature and professional consultation. Results: Only 23% of the patients were fully compliant with healthy lifestyle behaviors. About 95% were knowledgeable on hypertension and 86% had positive beliefs about the management protocols of their disease. Gender, physician counseling on a healthy lifestyle, patients’ beliefs about hypertension management, and their knowledge on hypertension and its management have an independent effect on compliance with lifestyle recommendations. Conclusion: Patients’ compliance with lifestyle recommendations was low. Receiving counseling from physicians about healthy lifestyle and self-care; being informed about hypertension and its management; and having positive beliefs about managing this disease are significant predictors of patients’ compliance with lifestyle recommendations.

Chronic kidney disease (CKD) modulates the nonrenal clearance of drugs by altering their metabolism and/or transport. While the effects of CKD on pathways of oxidative and conjugative metabolism in the liver are generally understood, the impact of CKD on hepatic reduction is not. Reduction is a critically important pathway for the metabolism of several drugs and endogenous compounds. Multiple clinical pharmacokinetic studies have reported changes in the disposition of hepatic reductase drug substrates in patients with CKD. More recently, data from experimental studies have shown that kidney disease alters the functional expression of hepatic reductases. Together, these data suggest that kidney disease may impair the nonrenal clearance of drugs mediated by reductive pathways. This review synthesizes the current evidence available regarding the effect of CKD on hepatic reduction. Areas for future investigations are also highlighted. The growing knowledge of the impact of impaired kidney function on nonrenal drug clearance may facilitate optimal drug therapy in this patient population.

Osama Y Alshogran,1 Karem H Alzoubi,1 Omar F Khabour,2 Shatha Farah2 1Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan; 2Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, Jordan University of Science and Technology, Irbid, Jordan Background and objective: Self-medication practice involves consumption of medicines by one’s own initiative or on the consultation of others without the guidance of a physician. Self-medication and use of over-the-counter drugs are prevalent worldwide public health concerns. University students of medical and nonmedical disciplines may have different levels of health education. This study evaluated the prevalence and patterns of self-medication and the attitudes toward this practice among medical and nonmedical university students in Jordan. Methods: A descriptive cross-sectional study was conducted in 504 students (medical: 248 and nonmedical: 256). The students were invited to complete a questionnaire that included questions primarily related to patterns of physician visits, self-medication practice, symptoms provoking self-medication, and sources of advice. Results: Self-medication was highly prevalent and comparable between medical and nonmedical students (~96%). Headache (81.9%), cold (58.3%), and flu (53%) were the frequent symptoms provoking self-medication among students. Self-medication for headache (86.7% vs 77.3%) and tooth pain (53.1% vs 27%) was significantly higher among medical vs nonmedical students, respectively. Self-treatment with painkillers (82.3% vs 73%) or antiallergy (11.3% vs 5.9%) drugs was significantly higher among medical students, while the use of anti-flu decongestants (47.6% vs 60.2%) was lower compared to nonmedical students, respectively. Nonmedical vs medical students were significantly more dependent on friends (14.8% vs 7.7%) and own experience (7.4% vs 2.4%) as a source of self-medication advice. Conclusion: Self-medication is common among Jordanian university students of medical and nonmedical disciplines. This practice, if used irrationally, may constitute a health problem that needs awareness and interventions by health care regulators in Jordan. Future studies are warranted to examine the impact of self-medication on students’ health. Keywords: self-medication, students, medical, nonmedical, survey, JordanA Letter to the Editor has been received and published for this article.&nbsp

Karem H Alzoubi,1 Zuhair Bani Ismail,2 Mohamed K AL-Essa,3 Osama Y Alshogran,1 Reem F Abutayeh,4 Nareman Abu-Baker5 1Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan; 2Department of Veterinary Clinical Sciences, Faculty of Veterinary Medicine, Jordan University of Science and Technology, Irbid, Jordan; 3Department of Physiology, Faculty of Medicine, University of Jordan, Amman, Jordan; 4Department of Medicinal Chemistry and Phytochemistry, Applied Science Private University, Amman, Jordan; 5Philadelphia Biomedical Products Development Center, Amman, Jordan Introduction: This study explored d-ribose pharmacokinetics after intravenous (IV) and oral administration to healthy rabbits. Materials and methods: D-ribose was administered once as 420 mg/kg (N=4) or 840 mg/kg (N=6) dose intravenously, or as an oral dose of 420 mg/kg (N=3) or 840 mg/kg (N=3). Serum was obtained at various time points, up to 210 minutes after administration. Urine was also collected after IV administration. Pharmacokinetic parameters were determined from drug concentration–time data using Kinetica software. Results: The findings showed that D-ribose follows a dose-dependent kinetic profile. With doubling the IV dose, AUCtotal was significantly increased by threefold, while the clearance was decreased by 44%. The half-life was 1.7-fold longer at the higher dose. Similar nonsignificant trends were also observed at oral administration. D-ribose was rapidly absorbed (Tmax=36–44 minutes) and rapidly disappeared from plasma (within

Authorship represents a critical element of scientific research. This study evaluated the perceptions, attitudes, and practices of Jordanian researchers toward the International Committee of Medical Journal Editors (ICMJE) authorship criteria. An anonymous questionnaire was distributed to health sciences faculty ( n = 986), with 272 participants completing the questionnaire. Only 27.2% reported awareness of ICMJE guidelines, yet, 76.8% agreed that all ICMJE criteria must be met for authorship, and 55.9% believed that it is easy to apply the guidelines. Unethical authorship practices were reported by 16.5% to 31.3% of participants. A majority (73%) agreed that violation of authorship criteria is scientific misconduct. Well-defined criteria for authorship need to be disseminated and emphasized in less developed countries through training to avoid authorship disputes and unethical conduct.

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.

Genetic variation in metabolizing enzymes contributes to variable drug response and disease risk. Aldo-keto reductase type 1C (AKR1C) comprises a sub-family of reductase enzymes that play critical roles in the biotransformation of various drug substrates and endogenous compounds such as steroids. Several single nucleotide polymorphisms have been reported among AKR1C encoding genes, which may affect the functional expression of the enzymes. Areas covered: This review highlights and comprehensively discusses previous pharmacogenetic reports that have examined genetic variations in AKR1C and their association with disease development, drug disposition, and therapeutic outcomes. The article also provides information about the effect of AKR1C genetic variants on enzyme function in vitro. Expert opinion: The current evidence that links the effect of AKR1C gene polymorphisms to disease progression and development is inconsistent and needs further validation, despite of the tremendous knowledge available. Information about association of AKR1C genetic variants and drug efficacy, safety, and pharmacokinetics is limited, thus, future studies that advance our understanding about these relationships and their clinical relevance are needed. It is imperative to achieve consistent findings before the potential translation and adoption of AKR1C genetic variants in clinical practice.

Chronic kidney disease (CKD) affects the nonrenal clearance of drugs by modulating the functional expression of hepatic drug-metabolizing enzymes and transporters. The impact of CKD on oxidative and conjugative metabolism has been extensively studied. However, its effect on hepatic drug reduction, an important phase I drug-metabolism pathway, has not been investigated. We aimed to assess the effect of experimental CKD on hepatic reduction using warfarin as a pharmacological probe substrate. Cytosolic and microsomal cellular fractions were isolated from liver tissue harvested from five-sixths-nephrectomized and control rats (n = 10 per group). The enzyme kinetics for warfarin reduction were evaluated in both fractions, and formation of warfarin alcohols was used as an indicator of hepatic reductase activity. Selective inhibitors were employed to identify reductases involved in warfarin reduction. Gene and protein expression of reductases were determined using quantitative real-time polymerase chain reaction and Western blotting, respectively. Formation of RS/SR-warfarin alcohol was decreased by 39% (P0.001) and 43% (P0.01) in cytosol and microsomes, respectively, in CKD rats versus controls. However, RR/SS-warfarin alcohol formation was unchanged in the cytosol, and a trend toward its decreased production was observed in microsomes. Gene and protein expression of cytosolic carbonyl reductase 1 and aldo-keto reductase 1C3/18, and microsomal 11β-hydroxysteroid dehydrogenase type 1 were significantly reduced by30% (P0.05) in CKD rats compared with controls. Collectively, these results suggest that the functional expression of hepatic reductases is selectively decreased in kidney disease. Our findings may explain one mechanism for altered nonrenal clearance, exposure, and response of drugs in CKD patients.

Psychological symptoms are prevalent in hemodialysis (HD) patients. Previous investigations showed that brain-derived neurotrophic factor (BDNF) and interleukin-6 (IL-6) as well as the interaction with neuropeptide S receptor 1 (NPSR1) are linked to the development of psychological distress. This study examined the association of polymorphisms of genes encoding these proteins with depression and anxiety in a representative group of Jordanian HD patients.A total of 302 HD patients were involved in the study and categorized into three groups based on the Hospital Anxiety and Depression Scale, HADS-D or HADS-A scores as follows: normal (7), mild (8-10) and moderate-severe (11-21). Single nucleotide polymorphism (SNP) of NPSR1 Asn107Ile (rs324981), IL-6 G174C (rs1800795), and BDNF Val66Met (rs6265) was genotyped using blood samples.The frequency of Ile-allele of NPSR1 Asn107Ile was significantly higher in patients with moderate-severe HADS-A scores versus normal (53% vs. 40.8%, p = .035). Using ordinal regression analysis, Asn-allele of NPSR1 polymorphism was nominally significantly associated with a lower risk of anxiety (OR = 0.57, CI: 0.33-0.97, p = .038) after adjusting for other covariates. A marginally significant difference in genotype distribution of IL-6 G174C was observed among patients according to HADS-D scores (p = .05). Furthermore, carriers of IL-6174 CC genotype showed lower median IL-6 serum concentration versus carriers of GG genotype (5.2 vs. 1.35 pg/mL, p .05).The results support the genetic role of NPSR1 in the pathogenesis of anxiety and suggest that carriers of NPSR1 Ile-allele are at increased risk of anxiety in HD patients. Neither BDNF Val66Met nor IL-6 G174C were linked to psychological symptoms. Future studies among other ethnicities are necessary to verify the observations.

A simple and rapid liquid chromatographic-tandem mass spectrometric method has been developed and validated for the enantiospecific determination of R- and S-warfarin in human urine. Warfarin enantiomers were extracted from urine using methyl tert-butyl ether. Chromatographic separation of warfarin enantiomers and the internal standard d5-warfarin was achieved using a Astec Chirobiotic V column with gradient mobile phase at a flow rate of 400 µL/min over 10 min. Detection was performed on a TSQ Quantum Ultra triple quadrupole mass spectrometer equipped with a heated electrospray ionization source. Analytes were detected in negative ionization mode using selected reaction monitoring. Calibration curves were linear with a correlation coefficient of ≥0.996 for both enantiomers over a concentration range of 5-500 ng/mL. The intra- and interday accuracy and precision for both analytes were within ±9.0%. Excellent extraction efficiency and negligible matrix effects were observed. The applicability of the method was demonstrated by successful measurement of warfarin enantiomers in urine of patients with kidney disease. The method is simple, accurate and reproducible and is currently being used to support warfarin pharmacokinetic studies.

The functional expression of several hepatic drug metabolizing enzymes and transporters are altered in patients with end-stage renal disease (ESRD). We aimed to assess the effect of ESRD on the expression and function of hepatic reductases. Cytosolic and microsomal fractions were isolated from liver tissue from deceased ESRD (n=10) and deceased control patients (n=11). Gene and protein expression, and metabolic activity of reductases were assessed by conducting qRT-PCR, Western blotting and enzyme kinetics, respectively. A 65% decrease in carbonyl reductase 1 protein expression (p

Background The human multi-drug resistance gene (MDR1), which encodes the major trans-membrane transporter P-glycoprotein (P-gp), was found to be associated with susceptibility to cancer and response to chemotherapy. The C3435T Polymorphism of MDR1 gene was correlated with expression levels and functions of P-gp. Here, we studied the association between MDR1 C3435T polymorphism and susceptibility to Hodgkin lymphoma (HL) and patient's response to ABVD chemotherapy regimen. Methods a total of 130 paraffin embedded tissue samples collected from HL patients were analyzed to identify the C3435T polymorphism. As a control group, 120 healthy subjects were enrolled in the study. The C3435T Polymorphism was genotyped by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. Data analysis was carried out using the statistical package SPSS version 17 to compute all descriptive statistics. Chi-square and Fisher exact tests were used to evaluate the genotype distribution and allele frequencies of the studied polymorphism. Results these studies revealed that the frequency of T allele was significantly higher in HL patients compared to the controls (P < 0.05). In addition, the frequency of CT and TT genotypes were also significantly higher in HL patients compared to the controls (P < 0.05). No association between C3435T polymorphism and response to ABVD was detected among HL patients (P > 0.05). Conclusions these results suggest that MDR1 C3435T polymorphism might play a role in HL occurrence; however this polymorphism is not correlated with the clinical response to ABVD.