Correlation of Plasma and Salivary Osteocalcin Levels with Nascent Metabolic Syndrome Components with and Without Pre/Diabetes Biochemical Parameters / Correlación de los niveles de osteocalcina en plasma y saliva con los componentes del síndrome metabólico naciente con y sin parámetros bioquímicos de prediabetes

Objectives: This study aimed to compare and correlate plasma and salivary levels of cardiometabolic risk biomarkers’ of pharmacotherapy (appraised using colorimetric assays), adiposity, and atherogenicity indices. Methods: 61 Nascent MetS subjects vs. 30 lean normoglycemic and healthy controls were recruited in Family Medicine outpatient clinics/Jordan University Hospital (a referral medical center). Fasting blood and saliva specimens were collected. Clinical and anthropometric variables were determined along with atherogenecity and adiposity indices. Results: Among nascent MetS (metabolic syndrome) recruits, almost half were normoglycemic, 43% were prediabetic and 8% were diabetic. Pronouncedly Glycemic (FPG and Alc) and lipid parameters (TG, HDL-C and non-HDL-C), adiposity indices (BMI, WHR, WtHR, Conicity-index, BAI, LAP, VAI) and atherogenicity indices (AIP, TC/HDL-C, LDL-C/HDL-C, non-HDL-C/HDL-C and TG/HDL-C) were higher in the nascent MetS group (P<0.05 vs. controls). Markedly among the plasma cardiometabolic risk biomarkers (P<0.05 vs. controls) in the nascent MetS group, adipolin, cathepsin S, ghrelin, irisin, LBP, leptin, and osteocalcin were higher but plasma FGF1 levels were oddly lower. Significantly (P<0.05 vs. controls) nascent MetS –linked salivary levels of adipolin and LBP were higher as opposed to the lower cathepsin S. Only osteocalcin, amongst 9 metabolic risk biomarkers studied, had remarkably significant correlation between plasma and saliva levels, in both total sample and MetS patients (P<0.05). Markedly in the nascent MetS only group, both plasma and salivary osteocalcin correlated with FPG and A1c (P<0.05); salivary osteocalcin correlated with BMI and LAP (P<0.05). Likewise, in the total sample plasma osteocalcin correlated significantly with BMI, BAI, WHt R, SBP, DBP, TG, LAP, VAI, TG/HDL-C and AIP (P<0.05), while salivary osteocalcin had substantial correlations only with FPG and A1c (P<0.05). Conclusion: Association of nascent MetS-related plasma and salivary osteocalcin levels and clinical characteristics and indices propagate salivary osteocalcin as a non-invasive marker for clinical control of MetS-/preDM.(AU)

Identification of Insulin Resistance Biomarkers in Metabolic Syndrome Detected by UHPLC-ESI-QTOF-MS.

Metabolic syndrome (MetS) is a disorder characterized by a group of factors that can increase the risk of chronic diseases, including cardiovascular diseases and type 2 diabetes mellitus (T2D). Metabolomics has provided new insight into disease diagnosis and biomarker identification. This cross-sectional investigation used an untargeted metabolomics-based technique to uncover metabolomic alterations and their relationship to pathways in normoglycemic and prediabetic MetS participants to improve disease diagnosis. Plasma samples were collected from drug-naive prediabetic MetS patients (n = 26), normoglycemic MetS patients (n = 30), and healthy (normoglycemic lean) subjects (n = 30) who met the inclusion criteria for the study. The plasma samples were analyzed using highly sensitive ultra-high-performance liquid chromatography electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS). One-way ANOVA analysis revealed that 59 metabolites differed significantly among the three groups (p < 0.05). Glutamine, 5-hydroxy-L-tryptophan, L-sorbose, and hippurate were highly associated with MetS. However, 9-methyluric acid, sphinganine, and threonic acid were highly associated with prediabetes/MetS. Metabolic pathway analysis showed that arginine biosynthesis and glutathione metabolism were associated with MetS/prediabetes, while phenylalanine, D-glutamine and D-glutamate, and lysine degradation were highly impacted in MetS. The current study sheds light on the potential diagnostic value of some metabolites in metabolic syndrome and the role of their alteration on some of the metabolic pathways. More studies are needed in larger cohorts in order to verify the implication of the above metabolites on MetS and their diagnostic value.

Population Pharmacokinetics Modeling of Lamotrigine in Jordanian Epileptic Patients Using Dried Blood Spot Sampling.

AIMS: To characterize the population pharmacokinetics of lamotrigine in Jordanian epileptic patients and to identify factors affecting therapeutic parameters. PATIENTS AND METHODS: A population pharmacokinetics model for lamotrigine was established based on a prospectively collected data of 52 steady-state concentrations from 38 adult and pediatric patients with epilepsy. Lamotrigine concentrations were determined by a dried blood spot liquid chromatography method. Data were analyzed according to a one-compartment model with first-order absorption and elimination using the nonlinear mixed effect modeling program. The covariates effect of total body weight, gender, age, and co-medication with topiramate, carbamazepine, phenytoin, phenobarbital, and valproic acid on lamotrigine clearance were investigated using a stepwise forward addition followed by a stepwise backward elimination. RESULTS: The final population pharmacokinetics model for lamotrigine clearance was as follows: CL/Fpop=θ1*exp (θ3*age)*exp (θ5*carbamazepine)*exp (θ6*valproic acid) , where θ1 is the relative clearance (L/hr) estimated, and θ3, θ5, and θ6 are the fixed parameters relating to age and co-medication with carbamazepine and valproic acid, respectively.The population mean value of lamotrigine total clearance generated in the final model (with covariates) was 2.12 L/hr. Inter-individual variability and residual unexplained variability expressed as the coefficient of variation was 37.1 and 26.1%, respectively. CONCLUSION: Lamotrigine total clearance in the Jordanian patients is comparable to that reported by others for Caucasian patients. Age and concomitant therapy with carbamazepine and valproic acid significantly affected lamotrigine clearance, and accounted for 48% of its inter-individual variability.

Perception of pharmacy students towards their community pharmacy training experience: a cross-sectional study from Jordan.

BACKGROUND: The fact that pharmacists are in the front line of patients' care gives a great responsibility to focus on education and training of pharmacy students to build a 'patient-centered' clinicians. Unfortunately, pharmacy education in the developing countries, have been lagging behind actual practice delivered by pharmacists. This highlighted the need to evaluate the perceptions of undergraduate pharmacy students regarding their current pharmacy training practices and experiences. METHODS: This is a cross-sectional study that was conducted in Jordan during the period from August 2018 to October 2018. During the study period, a questionnaire was distributed to pharmacy students to collect information regarding 1) pharmaceutical care services provided by them during their experiential training, 2) their perceptions towards training sites, 3) their perceptions of the outcomes of their training experience, 4) information about their training site and 5) their demographics characteristics. RESULTS: A total of 202 pharmacy students responded to the questionnaire. The majority of them reported having the opportunity to dispense refill or new prescriptions (73.8%, n = 149), and conduct patient interviews (69.8%, n = 141, but they were not provided good opportunities to create electronic patient profiles using the information obtained (53.0%, n = 107), perform required dose calculations based on patient information (37.6%, n = 76), and interact with other healthcare professionals (34.6%, n = 70). In addition, students showed positive attitudes toward training sites, positive feedback about the outcomes of their training experience (median scores range between 4 and 5 for all statements (IQR = 1 for all)). CONCLUSION: Students showed positive feedback about the outcomes of their training experience, but they felt that the selected training sites do not have adequate resources to meet their training competencies. Memorandums of understanding development is needed to specify the purpose of training and define the responsibility for both parties of the training process.

Prevalence of Cardiovascular Diseases Risk Factors among Jordanians.

BACKGROUND AND AIMS: One of the most common causes of death worldwide is cardiovascular diseases (CVDs). This study evaluated the prevalence of CVDs risk factors (RFs) and their constellation electively among the Jordanian population and, assessing the most prevalent RF interplay with the rest of CVDs RFs as well as the impact of age and gender dimorphism on the frequencies of coexistence of multiple CVDs risk factors (RFs) among the Jordanian population. METHODS AND RESULTS: In this observational multicenter study, a total of 1449 subjects were enrolled. The mean age (±SD) was 44.35 ± 14.46 years; 796 (54.9%) of them were females and 801 (55.28%) of the whole study pool had no family history of premature CVDs. Only 5.9% of the population did not have any of these RFs. The prevalence of CVDs MRFs within-affected subjects was as follows: there were 1081 (74.6%) subjects with overall dyslipidemia, 471 (32.51%) with obesity, 456 (31.47%) were smokers, and at the first diagnostic encounter 541 (37.47%) were with elevated blood pressure and, 310 (21.51%) were with elevated random blood sugar. The coexistence of ≥ two, ≥ three and, ≥ four RFs was observed in 75.7%, 44.4%, and 21.4% of the subjects, respectively. The constellation of multiple RFs was more frequent in men than that in women, where the presence of ≥ two RFs for men was at 86.18% vs. 67.09% for women. Similarly, the appearance of multiple RFs increases with age, starting from the existence of ≥ three, and four RFs respectively. Most notably the clustering of ≥ five RFs in the age group of 45-59 years showed the greatest frequency vs. any other age group. CONCLUSIONS: CVDs risk factors (RFs) and clusters of them are extremely prevalent in the Jordanian population. Overall dyslipidemia is the most prevalent MRF and the most favors clustering with other CVDs RFs. Combined two RFs had the highest proportional frequency between all six RFs clusters. The constellation of at least two, three, and four CVDs RFs presented at almost three-fourth, half, and around one-fourth; respectively, Middle-aged males presented significantly higher rates of ≥ five RFs occurrences than females.

A Pre-Post Study of Vitamin D Supplement Effects on Urinary Megalin: The Emerging Predictive Role of Megalin in Diabetic Nephropathy Progression.

INTRODUCTION: Megalin is a renal proximal tubular protein that reabsorbs vitamin D from glomerular filtrates. Previous studies found significantly higher levels of urinary megalin in chronic microvascular complications of diabetes with associated metabolic derangements. This study aimed at testing the effect of vitamin D supplements on urinary megalin levels in diabetic nephropathy (DN) patients with vitamin D hypovitaminosis. METHODS: Sixty-three participants with vitamin D deficiency and diabetic nephropathy (DN) were enrolled in the pre-post study; urinary megalin levels with various clinical parameters and serum levels of vitamin D3 were measured and compared to the baseline at 3- and 6-month intervals. RESULTS: Interestingly, a supplementation related increase in serum vitamin D3 levels at 3- and 6- month interventions affected a constellation of ameliorations in the DN progression of clinical and metabolic factors. There was a decrease in ACR with a concomitant decrease in urinary megalin and a decrease in blood pressure, fasting plasma glucose (FPG), and low-density lipoprotein - cholesterol (LDL-C) - but an increase in glomerular filtration rate (GFR). Principally, pellet urinary megalin associated positively (p < 0.05) with vitamin D hypovitaminosis and the albumin-to-creatinine ratio (ACR) but negatively (p < 0.05) with Ca2+ and body mass index (BMI). CONCLUSION: Vitamin D supplementation could elucidate underlying pathophysiological mechanisms and a prognostic significance of urinary megalin association with DN, obesity/MetS-related dyslipidemia, and hyperglycemia modification. Megalin is a putative sensitive and precise predictive marker and an emerging therapeutic target of renal anomalies.

Proportional correlates of adipolin and cathepsin S in metabolic syndrome patients with and without prediabetes.

BACKGROUND: Adipolin and cathepsin S are intricately involved in pathophysiology of metabolic syndrome (MetS) and prediabetes (PreDM). AIMS & METHODS: This cross-sectional study aimed to compare and correlate between these metabolic biomarkers as well as between them and adiposity, atherogenicity and hematological indices in MetS patients. Our cross-sectional study involved recruiting 29 normoglycemic MetS, 30 newly diagnosed drug naïve PreDM-MetS patients versus 29 lean, healthy and normoglycemic controls. RESULTS: Adipolin and cathepsin S plasma levels were significantly higher in both MetS (normoglycemic and PreDM) groups vs. healthy controls. Evidently proportional adipolin-cathepsin S association was markedly signified in 59 MetS participants (normoglycemic and PreDM). Distinctively unlike adipolin, inverse cathepsin S-diastolic blood pressure (DBP) but direct cathepsin S-monocyte count and its monocyte -to- lymphocyte ratio cross-correlated were marked. Notably unlike cathepsin S, adipolin was positively associated with each of FPG, A1C and TG, visceral adiposity index, lipid accumulation product and atherogenic index of plsama in the MetS pool of participants (N = 59). CONCLUSIONS: Given the intergroup discrepancies in adiposity, atherogenicity indices and their correlations (as well as hematological indices) with biomarkers; this cross-sectional study cannot rule out either biomarker as an associative predictor or as a surrogate indicator and putative prognostic tool for the prediction/prevention and treatment of metabolism dysregularities.

Increased irisin versus reduced fibroblast growth factor1 (FGF1) in relation to adiposity, atherogenicity and hematological indices in metabolic syndrome patients with and without prediabetes.

Background Irisin and fibroblast growth factor 1 (FGF1) are intricately involved in metabolic syndrome (MetS) and prediabetes (preDM) pathophysiology. This study aimed to compare and correlate irisin and FGF1 plasma levels, adiposity, atherogenicity and hematological indices in 29 normoglycemic MetS and 30 newly diagnosed drug naive prediabetic (PreDM) MetS patients vs. 29 lean and normoglycemic controls. Materials and methods Irisin and FGF1 plasma levels were measured using colorimetric assays. Intergroup comparisons were conducted by analysis of variance (ANOVA). Spearman's rank correlation was also examined. Results The mean circulating irisin levels (ng/mL) were significantly higher in the normoglycemic (but not prediabetic) MetS group (p < 0.01), while the mean circulating FGF1 levels (pg/mL) were markedly lower in the prediabetic (but not normoglycemic) MetS group (p < 0.05). Of note unlike FGF1, irisin in the MetS (both normoglycemic and prediabetic;N=59) groups correlated significantly and positively with each of waist circumference (WC), hip circumference (HC), body mass index (BMI), body adiposity index (BAI) and high-density lipoprotein-cholesterol (HDL-C) but not the non-HDL-C. Distinctively MetS-irisin negatively associated with the non-HDL-C/HDL-C ratio, total cholesterol (TC)/HDL-C ratio and the low-density lipoprotein-cholesterol (LDL-C)/HDL-C ratio, but positively with the red cell distribution width (RDW). In the same pool of 59 MetS reruits; Neither biomarker had a relationship with the visceral adiposity index (VAI), the lipid accumulation product (LAP), the conicity index (CI), the waist-hip ratio (WHR), the waist-to-height ratio (WHtR), the blood ratios or the atherogenicity index of plasma (AIP). Conclusions As any potential molecular crosstalk of irisin and FGF1 in MetS or its related dysregularities cannot be ruled out; Conversely the utility of irisin and FGF1 as surrogate prognostic biomarkers and putative pharmacotherapeutic targets in the predtion/prevention/management of diabetes and MetS is strongly suggested.

Correlates of resistin and retinol-binding protein 4 in metabolic syndrome patients with and without prediabetes.

Background Resistin and retinol-binding protein 4 (RBP4) can work in an intricate in metabolic syndrome (MetS) and prediabetes (PreDM) molecular crosstalk. Materials and methods Resistin and RBP4 were evaluated using colorimetric enzyme-linked immunosorbent assays (ELISAs) in 29 normoglycemic MetS, 30 newly diagnosed drug naïve MetS-preDM patients and 29 lean and normoglycemic controls. Results In this cross-sectional design; the gradual increase in resistin levels (ng/mL), though not ascribed any statistically marked variation, was appreciable in both normoglycemic and preDM MetS groups vs. controls. RBP4 mean circulating levels (ng/mL) in both MetS groups (non-diabetic and preDM) invariably lacked discrepancy vs. controls. Except for fasting plasma glucose (FPG) and A1C; no further intergroup discrepancy could be identified between MetS arms. Adiposity indices: body mass index (BMI), body adiposity index (BAI) and lipid accumulation product (LAP) (but not conicity index) were substantially higher in both MetS (non- and preDM) groups vs. those of controls. Likewise, the atherogenicity index of plasma [but not non-high-density lipoprotein-cholesterol (nonHDL-C)/HDL-C ratio, or triglyceride (TG)/HDL-C ratio] or any of the hematological indices [red cell distribution width (RDW-CV %), monocyte to lymphocyte ratio (MLR), neutrophil to lymphocyte ratio (NLR) and platelet (PLT) to lymphocyte ratios (PLR)] had any marked variations as compared to controls. Low-density lipoprotein-cholesterol (LDL-C)/HDL-C ratio,visceral adiposity index, and waist circumference (WC)/hip circumference (HC) ratio were noticeably greater in MetS-preDM vs. normoglycemic MetS recruits. Neither biomarker could relate to each other, or any of the atherogenecity indices in 59 MetS participants (non- and preDM). Unlike RBP4; resistin associated proportionally with each of HC, BAI, MLR and NLR. Conclusions Both biomarkers can be putative indicator/surrogate prognostic tools for the prediction/prevention and pharmacotherapy of MetS anomalies.

Correlates of zinc finger BED domain-containing protein 3 and ghrelin in metabolic syndrome patients with and without prediabetes.

Background Ghrelin and zinc finger BED domain-containing protein 3 (ZBED3) are distinctively cross linked with prediabetes (preDM) and metabolic syndrome (MetS). Materials and methods In a cross-sectional design with 29 normoglycemic MetS and 30 newly diagnosed drug naïve preDM/MetS patients vs. 29 lean and normoglycemic controls; ghrelin and ZBED3 were evaluated using colorimetric enzymatic assays. Results While ZBED3 mean circulating levels (ng/mL) in both MetS groups (normoglycemic and preDM) invariably lacked discrepancy vs. controls; Appreciably ghrelin levels (ng/mL) in preDM/MetS (but not normoglycemic MetS) participants were markedly higher vs. controls. Except for fasting plasma glucose (FPG) and glycosylated-hemoglobin (HbA1C); no further intergroup discrepancy could be identified between the MetS arms. Remarkably adiposity indices (body mass index (BMI), body adiposity index (BAI), and lipid accumulation product (LAP), but not conicity index (CI) or visceral adiposity index (VAI)); atherogenicity index of plasma (but not non-high-density lipoprotein-cholesterol (non-HDL-C/HDL-C) ratio, or total cholesterol (TC)/HDL-C ratio) or any of hematological indices (red cell distribution width (RDW-CV%), monocyte to lymphocyte ratio (MLR), neutrophil to lymphocyte ratio (NLR) and platelet (PLT) to lymphocyte ratio (PLR)) were substantially higher in both MetS (non- and preDM) groups vs. those of controls. Exceptionally low-density lipoprotein -cholesterol (LDL-C)/HDL-C ratio, and waist circumference (WC)/hip circumference (HC) ratio were much more pronounced in MetS-preDM vs. normoglycemic MetS recruits. In the MetS pool (both normoglycemic and preDM, n = 58), neither biomarker could relate to each other, or any of clinical parameters, adiposity or atherogenecity indices. Exceptionally ghrelin correlated significantly and inversely with age. ZBED3 correlated significantly and directly with RDW-CV% in the same pool of MetS recruits (n = 59). Conclusions Both biomarkers can not be ruled out as putative predictive/surrogate prognostic tools for metabolic anomalies prevention and pharmacotherapy.

Proportional correlates of cystatin-C with pentraxin-3, visceral adiposity index and atherogenicity index of plasma but not blood indices in metabolic syndrome patients with and without prediabetes.

Background Pentraxin-3 (PXT-3) and cystatin-C (Cys-C) are robustly related with central obesity and insulin resistance in prediabetes/metabolic syndrome (preDM-MetS). Materials and methods This cross-sectional study aimed to compare and correlate PXT-3 and Cys-C plasma levels in 29 normoglycemic MetS patients, 30 newly diagnosed drug naive preDM-MetS cases vs. 29 normoglycemic lean controls. Results Unlike PXT-3; Cys-C level was significantly higher in normoglycemic MetS (but not preDM-MetS) vs. healthy controls. Except for fasting blood glucose (FBG) and HbA1c; no further intergroup discrepancy could be identified between the MetS arms. Adiposity indices [body mass index (BMI), waist circumference (WC), hip circumference (HC), waist/height ratio (WHtR), body adiposity index (BAI) and lipid accumulation product (LAP) but not conicity index (CI)], atherogenicity index of plasma (AIP) (but not non-high density lipoprotein-cholesterol (nonHDL)-C, non-HDL-C/HDL-C ratio or total cholesterol (TC)/HDL-C ratio) or any of blood indices were substantially higher in both MetS (normoglycemic and preDM) groups vs. controls. Low density lipoprotein (LDL)-C/HDL-C ratio, visceral adiposity index (VAI) and WHR were exceptionally greater in MetS-preDM vs. controls. Marked proportional PTX-3-Cys-C correlation was noted in 59 MetS participants (normoglycemic and preDM). PTX-3 (but not Cys-C) correlated proportionally with each of neutrophils, monocyte/lymphocyte ratio and neutrophil/lymphocyte ratio but inversely with the lymphocyte count. Substantially, Cys-C (but not PXT-3) positively associated with both VAI and AIP but inversely with HDL-C. Neither biomarker in MetS pool had relations with red blood cell distribution width-coefficient of variation (RDW-CV%), BMI, WC, HC, CI, WHR, WHtR, BAI, LAP, non-HDL-C, ratios of non-HDL-C/HDL-C, LDL-C/HDL-C or TC/HDL-C. Conclusion PXT-3 and Cys-C can be surrogate prognostic/diagnostic biomarkers or putative MetS therapy targets.

Cross-sectional correlates of nesfatin and lipopolysaccharide binding protein in metabolic syndrome patients with and without prediabetes.

Background Metabolic syndrome (MetS) and prediabetes (preDM) have crosslinked pathophysiologies with central obesity and insulin resistance (IR). This study aimed to compare and correlate nesfatin and lipopolysaccharide binding protein (LBP) plasma levels, adiposity, atherogenicity and hematological indices between non-diabetic MetS, newly diagnosed drug naive pre-diabetic MetS patients vs. normoglycemic lean controls. Materials and methods In a cross-sectional study, 29 apparently healthy controls, 29 non-diabetic MetS subjects and 30 preDM-MetS patients were recruited. Results The LBP level (ng/mL) was substantially higher in both MetS (non- and pre-diabetic) groups compared to healthy controls. In contrast, circulating level of nesfatin (pg/mL) was lower, though not significantly; in both pre-diabetic and non-diabetic MetS patients compared to lean normoglycemic controls. No correlation was found between nesfatin and LBP in MetS pool (n = 59). Remarkably unlike blood indices; adiposity indices [body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height (WHtR) ratio, hip circumference (HC), body adiposity index (BAI), visceral adiposity index (VAI), lipid accumulation product (LAP) but not conicity index (CI)], atherogenicity indices [(atherogenicity index of plasma (AIP = Log10(TG/HDL-C ratio)), low density lipoprotein cholesterol to high density lipoprotein cholesterol ratio (LDL-C/HDL-C) and non-high density lipoprotein cholesterol (non-HDL-C)] were substantially higher in both MetS (non- and pre-diabetic) groups vs. those of controls. Exceptionally pronounced and proportional nesfatin-DBP and LBP-BAI correlations were identified in total MetS pool (both non-diabetic and pre-diabetic). Conclusions Nesfatin and LBP can be potential targets and surrogate biomarkers to use as putative prognostic/predictive tools for the prevention and treatment for MetS and related disorders.

Pharmacist's knowledge, practice and attitudes toward pharmacovigilance and adverse drug reactions reporting process.

BACKGROUND: Adverse drug reactions (ADRs) are a major cause of drug related morbidity and mortality. Pharmacovigilance is the science that plays an essential role in the reduction of ADRs, thus the evolution and growth of this science are critical for effective and safe clinical practice. OBJECTIVES: This study is considered the first study in the region to evaluate pharmacist's knowledge, practice and attitudes toward ADRs reporting after establishing the national ADRs reporting center in Jordan. METHOD: A cross sectional study was used to evaluate pharmacist knowledge and attitude toward ADRs reporting. A structured validated questionnaire was developed for this purpose and a total of 208 pharmacists were recruited to participate in this study. RESULTS: The majority of pharmacists have insufficient awareness and lack of knowledge about pharmacovigilance and ADRs reporting. Also the rate of reporting of ADRs was extremely poor. Several factors were found to discourage pharmacists from reporting ADRs, which include inadequate information available from the patient, unavailability of pharmacist ADRs form when needed, unawareness of the existence of the national ADRs reporting system. Also pharmacists think that ADRs are unimportant or they did not know how to report them. CONCLUSION: The results of this study suggest that pharmacists have insufficient knowledge about the concept of pharmacovigilance and spontaneous ADRs reporting. On the other hand, pharmacists had positive attitudes toward pharmacovigilance, despite their little experience with ADRs reporting. Educational programs are needed to increase pharmacist's role in the reporting process, and thus to have a positive impact on the overall patient caring process.

Evidence-based medicine use in pharmacy practice: a cross-sectional survey.

RATIONALE, AIMS AND OBJECTIVES: This study aimed to evaluate the awareness, attitude, knowledge and use of evidence-based medicine (EBM) among pharmacists in Jordan. METHODS: A cross-sectional self-reported survey was conducted on 122 pharmacists (both hospital and community) who were asked to fill a validated structured questionnaire. RESULTS: The participants showed a positive attitude towards EBM; more than 80% thought that EBM improves patient care, improves quick knowledge update, helps to unify the quality of care provided, is a good educational tool and a convenient source of advice. But despite this positive attitude, pharmacists showed partial understanding of the technical terms used in EBM; also they relied on their own judgment, medical representatives and standard textbooks in making their decision, resources that can no longer be considered sufficiently updated and/or evidence based. Patient overload, lack of personal time and limited access to EBM sources were the most commonly identified barrier to practicing EBM. Also this study suggest that pharmacist's experience is negatively associated with EBM knowledge score (Spearman's rho value -0.187, P-value 0.04). CONCLUSIONS: In spite of the positive attitude towards EBM, this study showed numerous personal and institutional barriers towards implementing EBM in Jordan, which necessitate immediate action by all health care decision makers to formulate a national plan to overcome such barriers, and to further investigate the evidence that teaching, learning and daily application of EBM in practice can improve the quality of care and reduce the cost.

Potassium canrenoate treatment in paediatric patients: a population pharmacokinetic study using novel dried blood spot sampling.

OBJECTIVE: To characterize the population pharmacokinetics of canrenone following administration of potassium canrenoate (K-canrenoate) in paediatric patients. METHODS: Data were collected prospectively from 37 paediatric patients (median weight 2.9 kg, age range 2 days-0.85 years) who received intravenous K-canrenoate for management of retained fluids, for example in heart failure and chronic lung disease. Dried blood spot (DBS) samples (n=213) from these were analysed for canrenone content and the data subjected to pharmacokinetic analysis using nonlinear mixed-effects modelling. Another group of patients (n=16) who had 71 matching plasma and DBS samples was analysed separately to compare canrenone pharmacokinetic parameters obtained using the two different matrices. RESULTS: A one-compartment model best described the DBS data. Significant covariates were weight, postmenstrual age (PMA) and gestational age. The final population models for canrenone clearance (CL/F) and volume of distribution (V/F) in DBS were CL/F (l/h) = 12.86 ×  (WT/70.0) × e [0.066 ×  (PMA - 40]) and V/F (l) = 603.30 ×  (WT/70) × (GA/40) where weight is in kilograms. The corresponding values of CL/F and V/F in a patient with a median weight of 2.9 kg are 1.11 l/h and 20.48 l, respectively. Estimated half-life of canrenone based on DBS concentrations was similar to that based on matched plasma concentrations (19.99 and 19.37 h, respectively, in 70 kg patient). CONCLUSION: The range of estimated CL/F in DBS for the study population was 0.12-9.62 l/h; hence, bodyweight-based dosage adjustment of K-canrenoate appears necessary. However, a dosing scheme that takes into consideration both weight and age (PMA/gestational age) of paediatric patients seems more appropriate.

Population pharmacokinetic model of canrenone after intravenous administration of potassium canrenoate to paediatric patients.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Little is known about the pharmacokinetics of potassium canrenoate/canrenone in paediatric patients WHAT THIS STUDY ADDS: A population pharmacokinetic model has been developed to evaluate the pharmacokinetics of canrenone in paediatric patients who received potassium canrenoate as part of their therapy in the intensive care unit. AIMS To characterize the population pharmacokinetics of canrenone following administration of potassium canrenoate to paediatric patients. METHODS: Data were collected prospectively from 23 paediatric patients (2 days to 10 years of age; median weight 4 kg, range 2.16-28.0 kg) who received intravenous potassium canrenoate (K-canrenoate) as part of their intensive care therapy for removal of retained fluids, e.g. in pulmonary oedema due to chronic lung disease and for the management of congestive heart failure. Plasma samples were analyzed by HPLC for determination of canrenone (the major metabolite and pharmacologically active moiety) and the data subjected to pharmacokinetic analysis using NONMEM. RESULTS: A one compartment model best described the data. The only significant covariate was weight (WT). The final population models for canrenone clearance (CL/F) and volume of distribution (V/F) were CL/F (l h(-1) ) = 11.4 × (WT/70.0)(0.75) and V/F (l) = 374.2 × (WT/70) where WT is in kg. The values of CL/F and V/F in a 4 kg child would be 1.33 l h(-1) and 21.4 l, respectively, resulting in an elimination half-life of 11.2 h. CONCLUSIONS: The range of estimated CL/F in the study population was 0.67-7.38 l h(-1) . The data suggest that adjustment of K-canrenoate dosage according to body weight is appropriate in paediatric patients.

Metronidazole population pharmacokinetics in preterm neonates using dried blood-spot sampling.

OBJECTIVES: To characterize the population pharmacokinetics of metronidazole in preterm neonates. PATIENTS AND METHODS: Data were collected prospectively from 32 preterm neonates who received intravenous metronidazole for the treatment of or prophylaxis against necrotizing enterocolitis. Dried blood spots (n = 203) on filter paper were analyzed by high-performance liquid chromatography, and the data were subjected to pharmacokinetic analysis performed by using nonlinear mixed-effect modeling. RESULTS: A 1-compartment model best described the data. Significant covariates were weight (WT) and postmenstrual age (PMA). The final population models for metronidazole clearance (CL) and volume of distribution (V) were: CL = 0.0247 × (WT/1.00)(0.75) × (1 + 0.107 × [PMA - 30]) and V = 0.726 × WT, where CL is in liters per hour, WT is in kilograms, PMA is in weeks, and V is in liters. This model predicts that the half-life of metronidazole decreases rapidly from ∼40 hours at 25 weeks' PMA to 19 hours at 32 weeks' PMA, after which it starts to plateau. This decrease in half-life is the result of a 5-fold increase in CL compared with only a 2.5-fold increase in V during the same period. CONCLUSIONS: Currently, there are no specific dose recommendations for metronidazole in preterm neonates. However, a dosing scheme for preterm neonates that takes into consideration both the weight and PMA has been suggested and should avoid administration of doses that are excessive or more frequent than necessary.

Development and validation of a dried blood spot-HPLC assay for the determination of metronidazole in neonatal whole blood samples.

A selective and sensitive high-performance liquid chromatography method with UV detection for the determination of metronidazole in dried blood spots (DBS) has been developed and validated. DBS samples [spiked or patient samples] were prepared by applying blood (30 microL) to Guthrie cards. Discs (6 mm diameter) were punched from the cards and extracted using water containing the internal standard, tinidazole. The extracted sample was chromatographed without further treatment using a reversed phase system involving a Symmetry(R) C18 (5 microm, 3.9 x 150 mm) preceded by a Symmetry(R) guard column of matching chemistry and a detection wavelength of 317 nm. The mobile phase comprised acetonitrile/0.01 M phosphate solution (KH(2)PO(4)), pH 4.7, 15:85, v/v, with a flow rate of 1 mL/min. The calibration was linear over the range 2.5-50 mg/mL. The limits of detection and quantification were 0.6 and 1.8 microg/mL, respectively. The method has been applied to the determination of 203 DBS samples from neonatal patients for a phamacokinetic/pharmacodynamic study.

Development and validation of a dried blood spot-LC-APCI-MS assay for estimation of canrenone in paediatric samples.

A selective and sensitive liquid chromatography (LC)-atmospheric pressure chemical ionisation (APCI)-mass spectroscopic (MS) assay of canrenone has been developed and validated employing Dried Blood Spots (DBS) as the sample collection medium. DBS samples were prepared by applying 30 microl of spiked whole blood onto Guthrie cards. A 6mm disc was punched from the each DBS and extracted with 2 ml of methanolic solution of 17alpha-methyltestosterone (Internal Standard). The methanolic extract was evaporated to dryness and reconstituted in acetonitrile:water (1:9, v/v). The reconstituted solution was further subjected to solid phase extraction using HLB cartridges. Chromatographic separation was achieved using Waters Sunfire C18 reversed-phase column using isocratic elution, followed by a high organic wash to clear late eluting/highly retained components. The mobile phase consisted of methanol:water (60:40, v/v) pumped at a flow rate of 0.3 ml/min. LC-APCI-MS detection was performed in the selected-ion monitoring (SIM) mode using target ions at m/z 341.1 and 303.3 for canrenone and internal standard respectively. The selectivity of the method was established by analysing DBS samples from 6 different sources (individuals). The calibration curve for canrenone was found to be linear over 25-1000 ng/ml (r>0.994). Accuracy (% RE) and precision (% CV) values for within and between day were <20% at the lower limit of quantification (LLQC) and <15% at all other concentrations tested. The LLOQ of the method was validated at 25 ng/ml. Clinical validation of the method was achieved by employing the validated method for analysis of 160 DBS samples from 37 neonatal and paediatric patients.