Population pharmacokinetics of vancomycin in patients with diabetic foot infection: a comparison of five models.

Purpose: This study aimed to compare individual pharmacokinetic (PK) parameters of vancomycin with predicted values from five population PK models in patients with diabetic foot infections (DFIs). Methods: Patients with a diagnosis of DFI and an estimated glomerular filtration rate (eGFR) ≥ 30 mL/min were included in the study. Individual PK data was carried on by collecting three vancomycin serum concentrations in a steady-state condition. Five published population-based nomograms were assumed to predict PK parameters. Optimal vancomycin exposure was considered as a trough level of 15-20 mg/L or the area under the curve over 24 h/minimum inhibitory concentration (AUC24/MIC) ≥ 400. Results: A total of 48 samples from 16 patients were analyzed. There was a statistically significant difference between the volume of distribution (Vd) obtained from population methods and the individual estimations (P ≤ 0.001 in Ambrose and Burton, P = 0.010 and 0.006 in Bauer and Burton revised models, respectively). AUC/MIC ≥ 400 was achieved in 68.7% of patients while 50% had a trough level of less than 15 mg/L. Conclusions: Vancomycin PK parameters, particularly individualized Vd, may not be predictable by population nomograms in patients with DFI and stable renal function. Moreover, the weak correlation between AUC24 values and trough concentrations underlines the starting practice of vancomycin AUC24-based monitoring and dosing in the clinical setting.

Impact of Obesity and Bariatric Surgery on Metabolic Enzymes and P-Glycoprotein Activity Using the Geneva Cocktail Approach.

The inter-individual variability of CYP450s enzyme activity may be reduced by comparing the effects of bariatric surgery on CYP-mediated drug elimination in comparable patients before and after surgery. The current research will use a low-dose phenotyping cocktail to simultaneously evaluate the activities of six CYP isoforms and P-gp. The results showed that following weight reduction after surgery, the activity of all enzymes increased compared to the obese period, which was statistically significant in the case of CYP3A, CYP2B6, CYP2C9, and CYP1A2. Furthermore, the activity of P-gp after surgery decreased without reaching a statistical significance (p-value > 0.05). Obese individuals had decreased CYP3A and CYP2D6 activity compared with the control group, although only CYP3A was statistically important. In addition, there was a trend toward increased activity for CYP1A2, CYP2B6, CYP2C9, and CYP2C19 in obese patients compared to the control group, without reaching statistical insignificance (p-value ≥ 0.05). After six months (at least), all enzymes and the P-gp pump activity were significantly higher than the control group except for CYP2D6. Ultimately, a greater comprehension of phenoconversion can aid in altering the patient's treatment. Further studies are required to confirm the changes in the metabolic ratios of probes after bariatric surgery to demonstrate the findings' clinical application. As a result, the effects of inflammation-induced phenoconversion on medication metabolism may differ greatly across persons and drug CYP pathways. It is essential to apply these results to the clinic to recommend dose adjustments.

Evaluating the Effects of Rivastigmine on Decision-Making in Patients with Mild Cognitive Impairment by Cambridge Neuropsychological Test Automated Battery (CANTAB); A Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Decision-making is a complex process, and most studies showed that patients with mild cognitive impairment (MCI) make worse decisions than healthy people. Objectives: This study aims to evaluate the effect of rivastigmine on the decision-making of MCI patients using the Cambridge Neuropsychological Test Automated Battery (CANTAB) tests. Methods: The study was conducted at the Roozbeh Hospital neurology clinic, and 30 patients with mild cognitive impairment over 40 years old were randomly recruited to receive rivastigmine or placebo twice daily for 12 weeks. The initial dose of rivastigmine or placebo was 1.5 mg twice daily and was increased to 3 mg twice daily per patient compliance. A CANTAB test was conducted before and following the intervention. Results: The mean age of patients in the rivastigmine group was 58.93 ± 10.88, and in the placebo group was 59.33 ± 10.34. The median MMSE (Mini-Mental State Examination) was 26 (IQR = 25 - 26) in both groups. Patients in the rivastigmine group showed significant differences in all subgroup tests of CGT, IST, and SST except in risk adjustment in the CGT test, discrimination in the IST test, and median correct RT on the go trial and SSRT in the SST test. The most commonly reported adverse effects were gastrointestinal complications. Conclusions: According to the results, rivastigmine significantly improved the primary decision-making outcomes in comparison with placebo.

Adverse drug reactions of Rituximab in patients suffering from autoimmune neurological diseases.

BACKGROUND: Rituximab, a chimeric human/mouse monoclonal antibody targeting CD-20 antigens, has been used recently for various rheumatological and autoimmune diseases, including autoimmune neurological disorders. OBJECTIVES: We aimed to study the frequency, seriousness, causality, and preventability of adverse drug reactions (ADRs) of rituximab in Iranian patients with autoimmune neurological diseases. METHODS: In this cross-sectional observational study, patients with autoimmune neurological diseases who had an indication for rituximab treatment were enrolled. Naranjo adverse drug reaction probability scale was used to assess the causality of ADRs, and the preventability of the ADRs was determined by P-Method. The seriousness of ADRs was also determined. RESULTS: A total of 264 ADRs were recorded from 97 patients. The Median (min-max) number of ADRs experienced by patients was 3 (1-7) events. 11.3% of patients experienced serious ADRs. 18.2% and 26.9% of ADRs were Definite and Probable, respectively. Only 5% of the ADRs were ''preventable". The most frequent ADRs were rituximab infusion-related reactions. CONCLUSION: Rituximab had an acceptable safety profile in our study patients. However, there must be certain cautions regarding the use of the medication for the elderly or patients with a compromised immune system. Timely detection and management of ADRs would also be crucial to prevent severe and permanent damages. Moreover, considering that rituximab is used as an off-label treatment for autoimmune neurological diseases, a risk-benefit assessment would be necessary before deciding on the treatment choice.

Datura poisoning in a family: Case series and literature review.

Datura spp. is a potentially poisonous plant that is widely spread and is simply accessible, which can yield poisoning with a central and peripheral anticholinergic effect. We reported cases of family poisoning caused by the herbal tea with refreshing effects that were identified as Datura spp.

The effects of vitamin D supplementation on postoperative atrial fibrillation after coronary artery bypass grafting in patients with vitamin D deficiency.

INTRODUCTION: Postoperative atrial fibrillation (POAF) as a common complication of coronary artery bypass grafting (CABG) surgery is associated with increased mortality and morbidity rates. Vitamin D deficiency increases the prevalence of POAF; however, the effects of vitamin D supplementation on the incidence of POAF have not yet been completely elucidated. METHODS: In this prospective, open-label, randomized clinical trial the level of 25-hydroxy vitamin D (25(OH) D) was measured in patients undergoing CABG surgery. Patients with vitamin D insufficiency (defined as 25(OH) D level < 30 ng/ml) were included and randomly assigned to control group to receive either the general standard of care (Group A) or to study group to receive the general standard of care plus oral vitamin D3 , 600,000 IU 5 days before surgery (Group B). The primary outcome of our study was the occurrence of POAF during the first 5 days after CABG surgery. RESULTS: Totally, 93 patients in group B and 103 patients in group A completed the study. The occurrence of POAF was significantly lower in group B as compared to group A (9.68% vs. 20.39%, p = .038). The length of intensive care unit (ICU) stay and hospital stay were reduced in group B patients (2.21 vs. 3.86 days, p < .001 and 7.40 vs. 9.58 days, p = .022, respectively). CONCLUSION: Our study demonstrated that vitamin D supplementation reduces the incidence of POAF, duration of ICU, and hospital stay following CABG surgery.

Identification of drug-related problems followed by clinical pharmacist interventions in an outpatient pharmacotherapy clinic.

WHAT IS KNOWN AND OBJECTIVE: Pharmacotherapy is an essential strategy for the treatment of many medical conditions especially chronic disease and often involves multiple medications being used simultaneously. Increasing the use of medications may pose some challenges to safe and effective drug therapy and if not identified and prevented by the pharmacists eventually can lead to drug-related problems (DRPs). The present study aimed to examine the incidence of DRPs in Iranian patients and to evaluate patients' adherence to the clinical pharmacist interventions as well as the physicians' acceptance of these recommendations. METHODS: This study was conducted in a university-affiliated outpatient pharmacotherapy clinic over a 22-month period. Patients aged 18 years and older with at least one chronic disease receiving at least four medications were included in the study. The patients were interviewed by a clinical pharmacist for comprehensive medication review. DRPs were identified using the DOCUMENT classification system. Recommendations were provided by the clinical pharmacist including interventions involving patient and/or physician to resolve DRPs. The patients were followed up after 2 weeks to evaluate their compliance and physician acceptance of clinical pharmacist recommendations. RESULTS AND DISCUSSION: Two hundred patients were included in this study. Overall, 875 DRPs were identified with an average of 4.37 per patient. The most prevalent DRPs were related to patient education or information (22.8%), undertreated indications (17.4%) and patient compliance (17.2%). The most common drugs associated with DRPs were alimentary and metabolism (22.2% of DRPs) followed by the cardiovascular system (19.2%) and nervous system (9.6%) medications. The DRP incidence correlated with gender only and was higher in females (p = 0.019). The clinical pharmacist provided 912 interventions with an average of 4.56 and 1.04 interventions per patient and per DRPs respectively. Patient education (41.3%), medication initiation or discontinuation (24.5%), and non-pharmacological interventions (12.9%) were the most common clinical pharmacist interventions. Out of 912 interventions, 665 were followed up, out of which 427 were patient dependent and 228 involved physicians. The patient's compliance with clinical pharmacist recommendations was 81.2%. The physician acceptance rate of the recommendations was 44.1%. WHAT IS NEW AND CONCLUSION: The study shows that especially designed services such as pharmacotherapy clinics running by clinical pharmacists are necessary to detect and resolve DRPs in an effective way. The high compliance rate of the patients indicates patients' confidence in the clinical pharmacist services provided in the pharmacotherapy clinic. The low acceptance rate of the physicians highlights the need to improve interprofessional collaboration between clinical pharmacists and physicians in an outpatient setting.

Comparing efficacy and safety of potassium hydroxide 5% solution with 5-fluorouracil cream in patients with actinic keratoses: a randomized controlled trial.

BACKGROUND: Actinic keratosis (AK) is a pre-cancerous skin lesion, associated with development of squamous cell carcinoma. Current treatment options are limited. OBJECTIVES: To compare the efficacy and safety of topical 5-fluorouracil cream (5-FU) and potassium hydroxide 5% (KOH) in the treatment of AK. METHODS: Eighteen patients with AK applied KOH solution or 5-FU on each side of their scalp/face, randomly. The efficacy and safety of these treatments were compared. RESULTS: Thirteen (118 lesions) and ten (83 lesions) patients were successfully followed for one and three months, respectively. After one month, KOH showed a better clinical response (81% vs. 58%; p-value = 0.007) and dermoscopic response (KOH, 65% vs. 5-FU, 46%; p-value = 0.04); while no differences were noted after three months (clinical response, 83% vs.70%, p-value = 0.1; dermoscopic response, 76% vs. 59%, p-value = 0.1). No significant differences in the recurrence rate of the lesion between the two groups were noted at the end of the third month (p-value = 0.5). Regarding the safety of the treatments, the risk of developing erythema, scaling, sand swelling was higher in 5-FU group (p-value < 0.0001, for all), while more patients in KOH group had erosion and ulcer (p-value < 0.001 for both). KOH was up to 96% less expensive than 5-FU. LIMITATIONS: Low number of patients and short-term follow-up limited the analysis. CONCLUSION: KOH solution offers a faster and less expensive resolution of AK lesions than does 5-FU. CLINICAL TRIAL CODE (IRCT.IR): IRCT20180909040978N1.

Evaluation of phenoconversion phenomenon in obese patients: the effects of bariatric surgery on the CYP450 activity "a protocol for a case-control pharmacokinetic study".

Personalized therapy suggests the appropriate drug at the right dose for the first time through genotype-based individualized therapy, instead of prescribing medicines by the traditional one-size-fits-all manner, thereby claiming that it will make medicines safer and more effective. Accordingly, polymorphisms of drug metabolizing enzymes (DMEs), which induce inter-individual variability in the pharmacokinetics of a drug, have attracted great interest in the context of personalized medicine. Obesity is one of the most common chronic diseases in the world, including Iran, and the prevalence is increasing according to predictions. The remarkable role of P450 cytochromes has been verified in the metabolism of numerous drugs, toxins, carcinogen compounds, and the synthesis of some intrinsic compounds, such as steroid hormones. Thus, evaluating the activity of these enzymes is of great importance because any functionality variation can lead to failure in the treatment or unwanted side effects of some drugs. Therefore, any change in the activity of these enzymes in obese patients can also be problematic in the treatment process of these patients in comparison to normal weighted ones. Since only a few human studies have examined the role of inflammation in altering the function of these enzymes, it seems to be necessary to investigate the effect of obesity on the expression and activity of these enzymes; in which the role of inflammatory processes has been proven. Most importantly, it is worth evaluating changes in the activity levels of cytochrome P450 (CYP450) and the inflammatory cytokines after a course of post-surgical treatment and weight loss. To evaluate the activity of CYPs, a multi-drug cocktail is prescribed to obese patients before and after obesity surgery, as well as to healthy volunteers, to provide simultaneous evaluation of different isoforms. A complete demographic data, medical examinations, laboratory tests, and the CYPs genotype of all participants can be extremely important during this investigation.

Effect of Selenium on Incidence and Severity of Mucositis during Radiotherapy in Patients with Head and Neck Cancer.

PURPOSE: Oral mucositis (OM) is the most frequent side effect of radiation. Selenium deficiency leads to increased levels of free oxygen radicals and the selenium level tends to fall during radiotherapy. Hence, in this double-blind randomised controlled clinical trial, the effect of selenium was assessed in patients receiving radiation. MATERIALS AND METHODS: Patients with head and neck cancer who were candidates to receive radiation were instructed to use selenium 200 mcg tablets twice daily. The grade of OM was evaluated by the World Health Organization (WHO) grading system on a weekly basis. The selenium level was measured at baseline and at the end of the radiation. RESULTS: Seventy-one patients with head and neck cancer (37 in the selenium group, 34 in the placebo group) were enrolled in the study. The cumulative incidence of OM (grade 1-4) was 97.3% in the selenium and 100% in placebo group (p value: 0.79), and difference in the mean serum selenium level at the end of radiation was not statistically significant between the two groups (p value 0.24) Conclusion: Selenium supplementation does not appear to affect the selenium level as well as the severity and duration of OM. It is supposed that higher doses may be effective in the prevention of RT-mucositis. This trial was registered in the Iranian Registry of Clinical Trials accessible at www.irct.ir (ID No. IRCT2014072718612N1).

Appropriateness of using granulocyte colony-stimulating factor (G-CSF) for primary prophylaxis of febrile neutropenia in solid tumors.

INTRODUCTION: Febrile neutropenia (FN) is one of the dose-limiting adverse effects of chemotherapy. Granulocyte-Colony Stimulating Factors (G-CSFs) minimize the incidence of FN and reduce the risk of neutropenia complications. This study was conducted to address the prescription pattern of G-CSF for primary prophylaxis of FN during the first cycle of chemotherapy in solid tumors. METHOD: This prospective observational study was done to investigate the G-CSF prescription pattern in patients receiving the first cycle of chemotherapy for solid tumors and compare it with the NCCN guideline recommendations. RESULT: Based on the guideline, prophylactic G-CSF administration was indicated in 26 of the 96 patients (27.1%) and all of them received G-CSF. On the other hand, 70 patients (72.9%) did not meet the guideline criteria for prophylaxis, but 60 (62.5%) of them received G-CSF. Seven doses of pegfilgrastim and 165 doses of filgrastim were used inappropriately in the study population, which was associated with an economic burden of about 224.7 million IRR (5350 USD). CONCLUSION: Taken together, inconsistencies with the guideline were observed in this prospective evaluation, suggesting that submitting rationalized policies to decrease G-CSF prescription, especially in patients with a lower or intermediate FN risk, yields substantial cost savings.

Oral calcitriol in hematopoietic recovery and survival after autologous stem cell transplantation: a randomized clinical trial.

BACKGROUND: Calcitriol, the active metabolite of vitamin D, is an essential regulator in the hematopoiesis and immunity. However, knowledge revealing its influence on the immune and hematologic reconstitution after hematopoietic stem cell transplantation (HSCT) in clinical trials is very limited. OBJECTIVES: The effects of calcitriol on short-term and long-term hematopoietic recovery, relapse-free survival (RFS) and overall survival (OS) in multiple myeloma, Hodgkin's and non-Hodgkin's lymphoma following autologous peripheral blood HSCT were assessed. METHODS: Eighty patients (age: 18-68 years) in complete remission were allocated 1:1 to two groups by balanced block randomization. Calcitriol 0.25 µg or placebo capsule was administered three times daily from transplantation to day 30. Absolute neutrophil count (ANC), absolute lymphocyte count (ALC), and platelet count (PC) were determined daily from transplantation to day 30. White blood cell count (WBC), PC, and hemoglobin concentration (HC) of days 180 and 365 were extracted from clinic files. A thorough examination for oral mucositis (OM) was completed daily during hospital stay. Adverse drug reactions (ADRs) as well as two-year RFS and OS were evaluated. RESULTS: Median time to ANC engraftment (≥0.5 × 103/µl: 10.0 vs. 11.0 days; P = 0.98) and PC engraftment (≥20.0 × 103/µl: both 14.0 days; P = 0.58) was similar between groups. However, the median time to ALC recovery was significantly shorter in the calcitriol group (≥0.5 × 103/µl: 13.0 vs. 20.0 days; P < 0.001). Moreover, ALC recovery rates on day 15 (≥0.5 × 103/µl: 82.1% vs. 42.5%; P < 0.001) and on day 30 (≥1.0 × 103/µl: 91.7% vs. 57.5%; P = 0.001) was significantly higher with calcitriol. WBC, PC, and HC on days 180 and 365 were not significantly different between groups. None of the OM indices were modulated by calcitriol. All the ADRs were non-serious and mild, possibly or unlikely related to the intervention. In a median of 29 months follow-up, RFS was significantly better in the calcitriol group (77.0%, SE = 7.0% vs. 59.0%, SE = 8.0%; P = 0.03), albeit the OS was not affected (87.0%, SE = 5.0% vs. 92.0%, SE = 4.0%; P = 0.72). CONCLUSION: Calcitriol could improve ALC recovery and RFS as a safe option post-HSCT. Graphical abstract Oral calcitriol 0.25 µg three times daily from transplantation to day 30 improved lymphocytes recovery and two-year relapse-free survival as a safe option in 80 patients of autologous hematopoietic stem cell transplantation in comparison with placebo.

Studying the Prevalence of Medical Interventions in the Recipes.

BACKGROUND: Drug interaction is a term used to refer to unfavourable side effects caused by mixing or taking two or more drugs simultaneously. Although it is not possible to identify all drug interactions, awareness of therapeutic team of potential drug interactions, risk factors that enhance the possibility of these interactions and familiarity with mechanisms of drug interactions can help reduce real drug interactions. AIM: The present research seeks to study the frequency and intensity of possible interactions among various age groups and their correlation with doctor's speciality, time of drug prescription, patient's gender, etc. MATERIAL AND METHOD: This is observational, cross-sectional research conducted in spring and winter to study the prevalence of drug interactions among 6000 recipes belonging to 2 private and 2 public drug stores. The information associated with recipes was recorded, and drug interactions were studied based upon quick index of interactions using Up to Date software. Quick index of medical interactions is a response to data dealing with how drugs interact with one another. The risk factor is divided into groups A, B, C, D, and X according to this index with each one having its own definition. The data analysis was studied in terms of prevalence type of drug interactions and the possible correlation with other parameters. SPSS v.16 was used for statistical analysis. RESULTS: The average age of the patients was 42.07 ± 21.56 years. The frequency of male patients was 41.7%. An average number of 4.82 ± 1.91 drugs were prescribed for each patient and an average number of 1.95 ± 2.40 drugs had interaction with one another with levels C, D, and X having the following drug interaction levels: 1.60 ± 2.05, 0.275 ± 0.69, and 0.072 ± 0.31. No such interactions were observed in 31.1% (1846 cases) of recipes. The presence of drug interaction was statistically significant in terms of age, season, drug store and speciality of doctor (P-value < 0.05). The average number of interactions in the recipes issued by psychologists, cardiologists, rheumatologist, neurologists, and general practitioners was more, and this result was statistically significant (P-value < 0.05). CONCLUSION: Considering the results achieved in this research, we may conclude that the drug interactions in recipes exhibit a noticeable frequency with the highest frequency observed in level C influenced by factors such as age, season, class of drugs, and expertise of the doctor.

Out of Pocket Payment and Affordability of Medication for Geriatric Patients in Tehran, Iran.

BACKGROUND: Considering the importance of high out-of-pocket (OOP) payment (OOPP), as a marker of health system performance, and affordability of medications in the elderly, this study was conducted to determine these issues. METHODS: In this cross-sectional study, prescriptions of patients aged 65 yr or older from 5 university-affiliated pharmacies in Tehran, Iran were evaluated from Jan to Mar 2014. Prescriptions were selected from four insurance organizations. We used the prescriptions data regarding patients' demographics and the prescribers as well as the sales data for OOP. Affordability was calculated by considering the daily salary of an unskilled worker. RESULTS: Totally, 1467 prescriptions were analyzed. Mean age of patients was 73.89(6.66) yr. Mean (SE) of reimbursable and OOPP of the prescriptions were 203820 (10831) and 230252 (10634) IRR (Iranian Rials) respectively (equivalent to 81.6 (4.33) and 92.17 (4.33) US$ respectively). Subspecialists imposed higher expenditures for patients and insurance organizations. Patients referred to the ophthalmologists paid less OOP. Nearly 50% of the total prescription costs was paid as OOP. The mean OOPP was averagely equal to 1.41(0.065) daily salary. These prescriptions were unaffordable for 36.2% of patients. CONCLUSION: The OOPP was higher than the insurance goal of 30% for outpatients in Iran. More than one-third of elderly patients could not afford their single prescription. Due to the health consequences of the unaffordability of medications, corrective actions are needed by the insurance organizations and the health system.

Significant drug interaction between voriconazole and dexamethasone: A case report.

BACKGROUND: Voriconazole is extensively metabolized by the CYP450 isoenzymes 2C19 and 3A4 and to a lesser extent by CYP2C9; therefore, any medication that affects this pathway can alter its plasma concentration. Treatment failure can probably occur if subtherapeutic levels are achieved. CASE DESCRIPTION: A 32-year-old woman who suffered from acute lymphoblastic leukemia was admitted and received treatment with vincristine and dexamethasone. After several days, to control her fever, based on two consecutive positive serum galactomannan test results, voriconazole as an antifungal agent was added to Aspergillus infection treatment. Through the first week after voriconazole initiation, its plasma concentrations were subtherapeutic. The most suspicious medication for interaction was dexamethasone, which can induce CYP450 isoenzymes and reduce plasma concentration. CONCLUSION: As a result of the narrow therapeutic window of voriconazole and the relationship between efficacy and plasma concentration of azoles, therapeutic drug monitoring of voriconazole in patients receiving a high dose of glucocorticoids is recommended, in order to achieve optimal response to treatment and toxicity reduction. Further studies regarding the interaction between voriconazole and dexamethasone to prevent clinically relevant interactions should be considered.

Prescribing for geriatrics in Tehran; is it appropriate and rational?

Background: The world's population is growing older. Inappropriate and irrational use of drugs in the elderly is a considerable health concern due to consequences such as increased morbidity and adverse drug events. This study aimed to evaluate the rationality of prescribing and determining the extent of inappropriate prescribing in a sample of geriatric patients in Tehran. Methods: This cross sectional study was performed on 1512 prescriptions of patients aged ≥ 65 years from 5 pharmacies affiliated to Tehran University of Medical Sciences in 2014. Prescription of potentially inappropriate medications (PIMs) was investigated using the Beers Criteria along with WHO prescribing indices. Date were analyzed using SPSS software, and significance level was set at less than 0.05. Results: Mean (SD) age of patients was 73.9(6.7) years. A total of 472 (31.2%) patients received at least 1 PIM. Benzodiazepines were the most frequent drug class and general practitioners (GPs) were the most frequent prescriber of PIMs. The highest and the lowest percentage of prescriptions containing brand-names were prescribed by subspecialists (62.5%) and GPs (42.2%), respectively. Antibiotics and injectable medications were prescribed for 26.8% and 28.5% of patients by GPs. Mean (SD) number of drugs per prescription was 3.57 (1.92). Prescriptions containing systemic antibiotics and PIMs had significantly higher mean number of drugs compared to those without these items (both P < 0.001). Conclusion: There is a need for interventions to improve the quality of prescribing for elderly patients, especially by GPs. Also, there are still some problems in rational use of drugs based on prescribing indices, especially, prescribing brand-names and injectable medications.

Comparison of Efficacy and Safety of Two Different Enoxaparin Products in Prevention of Venous Thromboembolism Following Major Obstetric-gynecological Surgeries: An Open-label Randomized Clinical Trial.

Venous thromboembolism (VTE) occurs in about 5 percent of patients undergoing major abdominal surgeries. Prophylaxis of VTE is recommended using unfractionated heparin (UF) or low molecular weight heparin (LMWH) in high-risk patients. In spite of advantages and confirmed cost-effectiveness of LMWH, high costs of enoxaparin branded preparations limit its use. We aimed to compare the efficacy and safety of two enoxaparin preparations. In this open-label randomized clinical trial, 200 patients were recruited to recieve PDxane® or Clexane®, 40 mg subcutaneously daily, from the day of surgery for 10 days. The patients were evaluated for VTE occurrence and side effects considering clinical and laboratory examinations at the beginning and day 10. No cases of proximal or distal VTE or life threatening bleeding were observed among 102 and 98 patients who received PDxane® and Clexane®, respectively. The adverse effects observed in PDxane® and Clexane® groups included injection site reactions (rash: P = 0.97; pain: P = 0.55 and erythema: P = 0.33), anemia (P = 0.32), hematuria (P = 0.16), confusion (P = 0.3), and increased liver transaminases (AST ≥ 3 × ULN: P = 0.16 and ALT ≥ 3 × ULN: P = 0.66). In according to the study results PDxane® was of similar efficacy and safety compared to Clexane® in preventing VTE following major obstetric-gynecological surgeries. Considering lower cost of PDxane®, it could be a safe and effective alternate for VTE prophylaxis in the patients undergoing such types of surgeries.

A Randomized Clinical Trial Evaluating the Efficacy of Colistin Loading Dose in Critically Ill Children.

OBJECTIVE: Pharmacokinetic and clinical studies recommend applying loading dose of colistin for the treatment of severe infections in the critically ill adults. Pharmacokinetic studies of colistin in children also highlight the need for a loading dose. However, there are no clinical studies evaluating the effectiveness of colistin loading dose in children. METHODS: In a randomized trial, children with ventilator-associated pneumonia or central line-associated bloodstream infection (CLABSI) for whom colistin was initiated, were enrolled. Patients were randomized into two groups; loading dose and conventional dose treatment arms. In the conventional treatment arm, colistimethate sodium was initiated with maintenance dose. In the loading dose group, colistimethate sodium was commenced with a loading dose of 150,000 international unit/kg, then on the maintenance dose. Both treatment arms also received meropenem as combination therapy. Primary outcomes were overall efficacy, clinical improvement and microbiological cure. Secondary outcomes were colistin-induced nephrotoxicity and development of resistance. FINDINGS: Thirty children completed this study. There was a significantly higher overall efficacy in the group received loading dose (42.9 vs. 6.3%, P = 0.031). There weren't any significant differences in the clinical and microbiological endpoints. In the subgroup of children with CLABSI, results illustrated a trend toward (though statistically nonsignificant) better clinical cure for patients receiving loading dose. CONCLUSION: This preliminary study suggests that colistin loading dose might have some benefits in critically ill children, specifically in children with CLABSI. Further trials are required to elucidate colistin best dosing strategy in critically ill children with severe infections.

Factors Affecting the Incidence and Severity of Oral Mucositis Following Hematopoietic Stem Cell Transplantation.

Background: Patients who receive hematopoietic stem cell transplantation (HSCT) experience several complications that oral mucositis (OM) is a frequent symptom. This study was designed to evaluate the incidence, risk factors, prophylaxis and treatment strategies for established OM. Materials and Methods: We included 173 adult patients who received autologous or allogeneic hematopoietic stem cell transplantation in this study. The World Health Organization oral toxicity scale was used to assess the severity of OM. Patients received two prophylactic regimens: regimen 1 contained nystatin, chlorhexidine, povidone iodine and amphotericin B. Regimen 2 contained nystatin and povidone iodine. 70 patients (40.5%) received the first prophylaxis regimen, 89 patients (51.4%) received the second prophylaxis regimen and the remaining 14 patients (8.1%) were not adherence to the use of the mouthwashes and were excluded from the analysis. Results: OM was detected in 60.7% of patients with mean (SD) age of 38.1±14.6 years. Multivariate analysis showed that only the female gender and the prophylactic regimen were the significant predictors of OM. Conclusion: We found that addition of amphotericin B and chlorhexidine, to the nystatin and povidone iodine resulted in a significant beneficial effect in prevention OM.

Choosing Appropriate Theories for Understanding Hospital Reporting of Adverse Drug Events, a Theoretical Domains Framework Approach.

Adverse drug events (ADEs) may cause serious injuries including death. Spontaneous reporting of ADEs plays a great role in detection and prevention of them; however, underreporting always exists. Although several interventions have been utilized to solve this problem, they are mainly based on experience and the rationale for choosing them has no theoretical base. The vast variety of behavioural theories makes it difficult to choose appropriate theory. Theoretical domains framework (TDF) is suggested as a solution. The objective of this study was to select the best theory for evaluating ADE reporting in hospitals based on TDF. We carried out three focus group discussions with hospital pharmacists and nurses, based on TDF questions. The analysis was performed through five steps including coding discussions transcript, extracting beliefs, selecting relevant domains, matching related constructs to the extracted beliefs, and determining the appropriate theories in each domain. The theory with the highest number of matched domains and constructs was selected as the theory of choice. A total of six domains were identified relevant to ADE reporting, including "Knowledge", "Skills", "Beliefs about consequences", "Motivation and goals", "Environmental context and resources" and "Social influences". We found theory of planned behavior as the comprehensive theory to study factors influencing ADE reporting in hospitals, since it was relevant theory in five out of six relevant domains and the common theory in 55 out of 75 identified beliefs. In conclusion, we suggest theory of planned behavior for further studies on designing appropriate interventions to increase ADE reporting in hospitals.