Evaluation of the Association between Trough and Area Under the Curve to Minimum Inhibitory Concentration Ratio (AUC24/MIC) of Vancomycin in Infected Patients with Methicillin Resistant Staphylococcus aureus (MRSA)

Background: The recent studies emphasized on the correlation of vancomycin antibacterial effect with pharmacokinetics properties such as the area under the curve/minimum inhibitory concentration (AUC24/MIC) ≥400 and serum trough level 15-20 mg /L in the patients with severe infection with methicillin-resistant Staphylococcus aureus (MRSA). The purpose is to assay the vancomycin pharmacokinetic properties in our population and evaluates the correlation between AUC24/MIC and trough serum level of vancomycin in given patients. Methods: The patients with a positive MRSA culture, treated with vancomycin, were enrolled in this cross-sectional study. Three plasma samples were obtained during the study including 30 min before fourth and the fifth dose as trough levels and 1 hour after the fourth dose as peak level to determine AUC24. E-TEST determined the MIC of vancomycin. Results: Thirty-eight patients with an average age of 48.33±16.44 were enrolled in this study. The mean ± SD of MIC was 0.99±0.30 mg/L. Thirty-four patients reached the adequate therapeutic range of AUC24/MIC ≥ 400 due to the standard vancomycin dosing method. In comparison, only 7 and 10 patients had the first and second trough levels in target intervals of 15-20 mg/L, respectively. Due to the receiver operating characteristic curve test (ROC test), the trough level after the fourth dose had a strong correlation with target AUC24/MIC with a sensitivity of 94.1%and specificity of 75.0%. Conclusion: This study concluded using only a trough level is not appropriate for therapeutic drug monitoring (TDM) of vancomycin. In our population, target AUC24/MIC (≥ 400) had a reasonably strong correlation with the trough level before the fifth dose which achieved with trough level ≥10.81 mg/L and MIC< 1 mg/L

Effect of Juglans regia L. Ridge on Blood Lipids in Type 2 Diabetic Patients with Dyslipidemia: A Double-blind Placebo-Controlled Randomized Clinical Trial

Background: Dyslipidemia and diabetes mellitus are two important risk factors for coronary artery disease and stroke. Traditionally, herbal remedies like walnut were used to treat dyslipidemia. The study aimed to evaluate the effect of Juglans regia L. (J. regia L.) internal septum extract (ISE) on lipid profile of patients with type 2 diabetes. Methods: After preparing hydroalcoholic ISE, Folin-Ciocalteau (FC) and AlCl3 colorimetric methods were used to determine total phenolic content (TPC) and total flavonoid content (TFC), respectively. In a randomized, double-blind placebo-controlled trial, 86 diabetic patients with dyslipidemia were randomly divided into equal groups and received ISE or placebo capsules 1500 mg/day for 12 weeks. Lipid profile, LFT, SCr, urea, hemoglobin A1c (HbA1c), blood pressure (BP), weight, waist and waist to hip ratio (WHR) were determined at baseline and after 12 weeks. The paired sample t-test and independent sample t-test were performed to compare the differences within and among the groups, respectively. This study was registered in the Iranian registry of clinical trials (IRCT ID: IRCT20201227049850N1). Results: The mean (SD) of TPC and TFC were measured based on 74.57 (5.20) milligram gallic acid equivalent/gram of dry extract (mg GAE/g DE) and 14.11 (2.73) mg quercetin equivalent/g of DE (mg QE/g DE), respectively. During the trial, 26 patients lost follow-up, and the study continued with remaining 60 patients. After intervention, there were no significant differences in LDL-C (p=0.44), total cholesterol (TC) (p=0.42), high-density lipoprotein cholesterol (HDL-C) (p=0.99), triglyceride (TG) (p =0.32) and Lp(a) (p=0.55) between two groups. Moreover, no significant (p>0.05) changes were observed in HbA1c, LFT, SCr, urea, BP, weight, waist, and WHR among the groups after 12 weeks. Conclusion: Our findings showed J.regia L. ISE had no significant effect on lipid profile compared to placebo. Moreover, no adverse effect was observed on liver and kidney function tests

The hypoglycemic effects of Juglans regia L. internal septum in type 2 diabetic patients: A double-blind, randomized, placebo-controlled clinical trial

Introduction: The internal septum of J.regia is traditionally used to control diabetes, and its effectiveness has been shown in animal studies. Accordingly, human clinical trials are needed to confirm its effectiveness on hemoglobin A1c (HbA1c), fasting blood sugar (FBS), blood insulin level, and insulin resistance as a complementary for better control of type 2 diabetes. Methods: This study was a randomized, double-blinded, controlled trial. The lyophilized powder of extract of the internal septum of J.regia was used to fill the capsules. Sixty type 2 diabetic patients were randomly divided into two groups. 500 mg capsules three times daily before meal was added to their routine drug regimen, and HbA1c, FBS, and blood insulin level were checked at the baseline and after three months. Results: Sixty patients completed the study. The mean(±SD) age of patients was 49.1(10.2) and 50.9(12.7) years in the placebo and J.regia groups, respectively. We observed that J.regia internal septum increases the level of HbA1c by about 0.02 units, but this effect was not significant (MD=0.02,95%CI=-0.36 to 0.40, P=0.93). Regarding the impact of capsules on insulin level, it seems that J.regia-containing capsules can raise insulin level by one unit. However, it was not significant (MD=1.01,95%CI=-0.86 to 2.88, P=0.28). As for FBS, it can cause a decrease of four units, but this effect is also not significant (MD=-3.98,95%CI=-18.33 to 10.37, P=0.58). Conclusion: Based on our study, the internal septum of J.regia has no significant effect on HbA1c, FBS, and insulin resistance. Moreover, no specific adverse reaction was observed in any of the patients

Role of Pharmacogenomics in Statin Responsiveness; A Review

Statins have been used for decades as a successful cholesterol-lowering class of medicines. Statins are widely prescribed for the primary and secondary prevention of coronary artery disease. They reduce cardiovascular risk and improve health outcomes in people with cardiovascular disease. Although statins re considered as a safe medicine and are well tolerated by patients, prediction of an individual patient’s response to statin therapy remains unclear. Variation to statin therapy has been attributed to both environmental and genetic factors. In this review, a number of candidate genes that affect statin pharmacokinetics and pharmacodynamics are discussed. Moreover, the association of demographic factors with statin response in related studies is described. In this article we have reviewed the literature concerning pharmacogenetic studies on statin response. Thirty seven English-language clinical trials, prospective or retrospective human investigations, case series, case reports, published between 1998 to 2015, were evaluated. Based on these data, there are some candidate genes that have been established as affecting genes on statin efficacy and suggest that drug therapy, based on individuals’ genetic makeup, may result in a clinically important reduction in variation of statin response

Case Presentation of a 45 Years Old Woman with Hypoglycemia and Bleeding: A case with hypoglycemia and bleeding

Apatient was admitted to the hospital because of epistaxis, ecchymoses and gum bleeding with INR of 5.5. This patient had a known case of diabetes mellitus type II, 5 years ago. The last dose of glibenclamide for managing signs and symptoms of diabetes mellitus was 20 mg/day. Her medical history also showed that last month she was diagnosed with atrial fibrillation with normal left ventricular ejection fraction (LVEF> 45%) and was placed on warfarin (5 mg) and propranolol (80 mg) daily, which resulted in resolution of atrial fibrilation, a pulse rate of 80 bps and INR of 3 (target INR=2-3). An objective causality assessment indicated the increased effect of warfarin and as a result bleeding could best be explained by drug-drug interaction because there are no other factors such as pathological evidences (e.g. thyroid disease, hepatic disorders) to prove it otherwise. This case is the third report of drug interaction between warfarin and glibenclamide, therefore, this is an interesting and educational case.In view of our experience in the present case, it should be stressed that close monitoring of coagulation capacity is necessary in co-administration of warfarin and other drugs which can affect pharmacokinetic and pharmacodynamic of warfarin.&nbsp

Effect of Demographic and Clinical Factors on New- Onset Diabetes Mellitus after Liver Transplantation in Iranian Patients

BACKGROUNDS: New- onset diabetes after transplantation (NODAT) is a serious complication which runs the risk of infections, morbidity and mortality. Older age, male sex, immunosuppressive agents and hepatitis C are reported as risk factors. The focus of this research is evaluating some demographic and clinical factors in development of NODAT in hepatic transplanted patients. This study aims to help identifying high risk recipients in order to prevent NODAT and improve transplantation prognosis. METHODS: In this study 134 liver recipients without pre- transplantation diabetes were investigated; 70 euglycemic and 64 with NODAT within 2 years after transplantation. All the patients were on tacrolimus- based immunosuppressive regimen. The role of recipients’ age, sex, body mass index (BMI), model for end- stage liver disease (MELD) score, blood group, diseases leading to transplantation, tacrolimus dose and serum level, mycophenolate mofetil (MMF) and prednisolone dose in the incidence of NODAT were assessed. RESULTS: The prevalence of NODAT in this study was 17.92%. The means of duration after transplantation that NODAT occurred, was 98.36± 21.62 days. The mean age of all patients was 37.83±16.26 years and 60.40% were females. Two groups were similar in terms of pre- transplantation fasting blood sugar (FBS) (P=0.091). Age (P=0.001,OR=1.063,CI:1.025-1.102) and prednisolone dose (P<0.0001,OR=1.270,CI:1.163-1.388) the only independent predictors of NODAT, while tacrolimus daily dose and plasma level, MMF daily dose, sex, BMI and underlying diseases were not risk factors for NODAT. CONCLUSIONS: Recipients with older age and higher prednisolone dose are more prone to NODAT and need more accurate monitoring

Comparison of antiplatelet activity of garlic tablets with cardio-protective dose of aspirin in healthy volunteers: a randomized clinical trial

Objective: Some of the adverse effects of aspirin including peptic ulcers, gastrointestinal bleeding and aspirin resistance compelled researchers to find a suitable alternative with fewer adverse effects. In this clinical trial, we aimed to find the effective antiplatelet dose of garlic. Materials and Methods: This randomized controlled clinical trial (RCT) was conducted on 62 healthy volunteers of 20-50 years old. All volunteers used 80 mg aspirin per day for 1 week and at the end of this time, platelet aggregation (PA) induced by 4 agonists acting in aggregation pathway including adenosinediphosphate (20 μmol/l), epinephrine (20 μmol/l), collagen(0.19 mg/ ml) and arachidonic acid (0.5mg/ ml) was measured by Light Transmittance Aggregometry (LTA) in all participants. After one month washout period, volunteers were randomized into 3 groups and each received 1, 2 or 3 garlic tablets (1250 mg) a day for 1 month. After one month, PA was examined in all groups. Results: The mean ±SD of the age of all volunteers was 28.60 ± 9.00 years. In addition, 52.00 % of our volunteers were male and 48.00% of them were female. Garlic tablet didnot have significant effect on PA at any dose. However, 30% of volunteers in the group that used 3 garlic tablets/day reported adverse effect (i.e. bleeding). No significant association between sex, age and PA was observed. Conclusion:  In this study, we were unable to determine the effective anti-platelet dose of garlic which that could be equal to that of aspirin anti-platelet activity, as assessed LTA method

Design, implementation, and evaluation of a diabetes educational game for the pharmacy students: A parallel-group study

Background & Objective: The objectives of this study were to design, implement, and evaluate an educational game on the diagnosis and management of diabetes for pharmacy students. Materials & Methods: Educational content for diabetes was prepared and used to design a multimedia file and game scenario. The game was validated and consisted of 25 stages of diagnosing and managing diabetes. Participants were 8th-semester pharmacy students who were divided into two groups. Groups A and B had 10-day access to the multimedia and game files, respectively. Pretest and post-test were held to evaluate students’ learning, and the final exam was used to assess retention. Moreover, user experience was evaluated by a modified and validated version of the Model for the Evaluation of Educational Games questionnaire. Results: A total of 154 students participated in the study. The mean ranks were 69.25 and 60.99 (P=0.808) in the pretest; 64.80 and 67.63 (P=0.551) in the post-test; and 67.44 and 62.19 (P=0.490) in the final exam for groups A and B, respectively. Ninety-nine participants completed the quality questionnaire of the study. The students confirmed the quality of the game in nearly all quality dimensions. About 80 percent of the game users preferred it over usual teaching methods. Conclusion: A high-quality educational game for diabetes was designed and implemented. Although the use of the game was not associated with increased learning or retention scores, pharmacy students preferred it over traditional teaching methods

Incidence of Potential Drug-Drug Interaction and Related Factors in Hospitalized Neurological Patients in two Iranian Teaching Hospitals

Background: Reciprocal drug interactions are among the most common causes of adverse drug reactions. We investigated the incidence and related risk factors associated with mutual drug interactions in relation to prescriptions written in the neurology wards of two major teaching hospitals in Shiraz, southern Iran. Methods: Data was collected from hand-written prescriptions on a daily basis. Mutual drug interactions were identified using Lexi-Comp 2012 version 1.9.1. Type D and X drug interactions were considered as potential drug-drug interactions. The potential risk factors associated with drug-drug interactions included the patient’s age and gender, number of medications and orders, length of hospitalization and the type of neurological disorder. To determine potential drug-drug interactions, relevant interventions were suggested to the physicians or nurses and the outcome of the interventions were documented. Results: The study comprised 589 patients, of which 53% were males and 47% females, with a mean age of 56.65±18.19 SD years. A total of 4942 drug orders and 3784 medications were prescribed among which 4539 drug-drug interactions were detected, including 4118 type C, 403 type D, and 18 type X. Using a logistic regression model, the number of medications, length of hospitalization and non-vascular type of the neurological disorder were found to be significantly associated with potential drug-drug interactions. From the total interventions, 74.24% were accepted by physicians and nurses. Conclusion: Potentially hazardous reciprocal drug interactions are common among patients in neurology wards. Clinical pharmacists can play a critical role in the prevention of drug-drug interactions in hospitalized patients

A Case of Ciprofloxacin-Induced QT Prolongation and Torsade de Pointes

Prolongation of the QT interval is a recognized adverse effect of fluoroquinolone antibiotics. This effect on ventricular repolarization can potentially lead to life-threatening arrhythmias such as Torsade de pointes. Torsade de pointes is a polymorphic form of ventricular tachycardia identified by twisting of the QRS axis around an isoelectric point. We report a case of torsade de pointes induced by ciprofloxacin treatment. The patient experienced an acquired QT interval prolongation followed by Torsade de pointes arrhythmia with ciprofloxacin administration for ileostomy closure surgery and unfortunately expired