Improving adverse drug event reporting by healthcare professionals.

BACKGROUND: Adverse drug events, encompassing both adverse drug reactions and medication errors, pose a significant threat to health, leading to illness and, in severe cases, death. Timely and voluntary reporting of adverse drug events by healthcare professionals plays a crucial role in mitigating the morbidity and mortality linked to unexpected reactions and improper medication usage. OBJECTIVES: To assess the effectiveness of different interventions aimed at healthcare professionals to improve the reporting of adverse drug events. SEARCH METHODS: We searched CENTRAL, Embase, MEDLINE and several other electronic databases and trials registers, including ClinicalTrials.gov and WHO ICTRP, from inception until 14 October 2022. We also screened reference lists in the included studies and relevant systematic reviews. SELECTION CRITERIA: We included randomised trials, non-randomised controlled studies, controlled before-after studies, interrupted time series studies (ITS) and repeated measures studies, assessing the effect of any intervention aimed at healthcare professionals and designed to increase adverse drug event reporting. Eligible comparators were healthcare professionals' usual reporting practice or a different intervention or interventions designed to improve adverse drug event reporting rate. We excluded studies of interventions targeted at adverse event reporting following immunisation. Our primary outcome measures were the total number of adverse drug event reports (including both adverse drug reaction reports and medication error reports) and the number of false adverse drug event reports (encompassing both adverse drug reaction reports and medication error reports) submitted by healthcare professionals. Secondary outcomes were the number of serious, high-causality, unexpected or previously unknown, and new drug-related adverse drug event reports submitted by healthcare professionals. We used GRADE to assess the certainty of evidence. DATA COLLECTION AND ANALYSIS: We followed standard methods recommended by Cochrane and the Cochrane Effective Practice and Organisation of Care (EPOC) Group. We extracted and reanalysed ITS study data and imputed treatment effect estimates (including standard errors or confidence intervals) for the randomised studies. MAIN RESULTS: We included 15 studies (eight RCTs, six ITS, and one non-randomised cross-over study) with approximately 62,389 participants. All studies were conducted in high-income countries in large tertiary care hospitals. There was a high risk of performance bias in the controlled studies due to the nature of the interventions. None of the ITS studies had a control arm, so we could not be sure of the detected effects being independent of other changes. None of the studies reported on the number of false adverse drug event reports submitted. There is low-certainty evidence suggesting that an education session, together with reminder card and adverse drug reaction (ADR) report form, may substantially improve the rate of ADR reporting by healthcare professionals when compared to usual practice (i.e. spontaneous reporting with or without some training provided by regional pharmacosurveillance units). These educational interventions increased the number of ADR reports in total (RR 3.00, 95% CI 1.53 to 5.90; 5 studies, 21,655 participants), serious ADR reports (RR 3.30, 95% CI 1.51 to 7.21; 5 studies, 21,655 participants), high-causality ADR reports (RR 2.48, 95% CI 1.11 to 5.57; 5 studies, 21,655 participants), unexpected ADR reports (RR 4.72, 95% CI 1.75 to 12.76; 4 studies, 15,085 participants) and new drug-related ADR reports (RR 8.68, 95% CI 3.40 to 22.13; 2 studies, 7884 participants). Additionally, low-certainty evidence suggests that, compared to usual practice (i.e. spontaneous reporting), making it easier to report ADRs by using a standardised discharge form with added ADR items may slightly improve the total number of ADR reports submitted (RR 2.06, 95% CI 1.11 to 3.83; 1 study, 5967 participants). The discharge form tested was based on the 'Diagnosis Related Groups' (DRG) system for recording patient diagnoses, and the medical and surgical procedures received during their hospital stay. Due to very low-certainty evidence, we do not know if the following interventions have any effect on the total number of adverse drug event reports (including both ADR and ME reports) submitted by healthcare professionals: - sending informational letters or emails to GPs and nurses; - multifaceted interventions, including financial and non-financial incentives, fines, education and reminder cards; - implementing government regulations together with financial incentives; - including ADR report forms in quarterly bulletins and prescription pads; - providing a hyperlink to the reporting form in hospitals' electronic patient records; - improving the reporting method by re-engineering a web-based electronic error reporting system; - the presence of a clinical pharmacist in a hospital setting actively identifying adverse drug events and advocating for the identification and reporting of adverse drug events. AUTHORS' CONCLUSIONS: Compared to usual practice (i.e. spontaneous reporting with or without some training from regional pharmacosurveillance units), low-certainty evidence suggests that the number of ADR reports submitted may substantially increase following an education session, paired with reminder card and ADR report form, and may slightly increase with the use of a standardised discharge form method that makes it easier for healthcare professionals to report ADRs. The evidence for other interventions identified in this review, such as informational letters or emails and financial incentives, is uncertain. Future studies need to assess the benefits (increase in the number of adverse drug event reports) and harms (increase in the number of false adverse drug event reports) of any intervention designed to improve healthcare professionals' reporting of adverse drug events. Interventions to increase the number of submitted adverse drug event reports that are suitable for use in low- and middle-income countries should be developed and rigorously evaluated.

DRESS Syndrome Induced by Sorafenib in a Patient With Medullary Thyroid Cancer: A Case Report.

Background: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare and life-threatening hypersensitivity reaction. It is characterized by fever, skin lesions, and internal organ involvement. Sorafenib is a tyrosine kinase inhibitor that is used for the treatment of certain cancers such as hepatocellular, renal cell, and thyroid cancer. Case Presentation: The case is a 40 years old man who presented with fever, generalized skin rash, and pruritus. The patient has received sorafenib for the treatment of medullary thyroid cancer (MTC) from 3 weeks ago. Following presentation, the drug was discontinued and causality was assessed by scoring system RegiSCAR and Naranjo scale that showed a probable DRESS. There was no internal organ involvement based on the laboratory evaluations. The considerable abnormality was eosinophilia among patient's laboratory tests. Antihistamines and topical and systemic corticosteroids were utilized for the management of the symptoms. Conclusion: To the best of our knowledge, this is the first case report of DRESS syndrome by sorafenib in the patients with MTC. Clinicians should be aware of sign and symptoms suggesting DRESS syndrome of sorafenib.

Iranian consensus on use of vitamin D in patients with multiple sclerosis.

BACKGROUND: Accumulating evidences from experimental, epidemiologic and clinical studies support the potential linkage between poor vitamin D status and the risk of developing Multiple Sclerosis (MS), as well as, an adverse disease course. However, the results of the trials on the clinical outcomes of vitamin D supplementation in MS patients are less consistent which brought many discrepancies in routine practice. In this article we presented a summary of a symposium on vitamin D and MS. In this symposium we aim to review the current data about the relationship between vitamin D and MS, and suggest management guides for practicing neurologists. DISCUSSION: Generally, supplementation seems to be reasonable for all MS and clinically isolated syndrome (Rinaldi et al., Toxins 7:129-37, 2015) patients with serum 25(OH)D level below 40 ng/ml. In patients with vitamin D insufficiency or deficiency, a large replacing dose (e.g. 50,000 IU capsules of D per week for 8-12 week) is recommended. Panel also suggested: the checking of the serum vitamin D, and calcium level, as well as, patients' compliance after the initial phase; a maintenance treatment of 1500-2000 IU daily or equivalent intermittent (weekly, biweekly or monthly) Dose, considering the patient's compliance; routine check of serum vitamin D level at least two times a year especially at the beginning of spring and autumn; Serum vitamin D evaluation for first degree relatives of MS patients at high risk age and supplementation in case of insufficiency (25(OH)D less than 40 ng/ml); correction of vitamin D deficiency and insufficiency before pregnancy, as well as, a daily dose of 1500-2000 IU or equivalent biweekly intake in 2nd and 3rd trimesters; stopping supplementation if 25(OH)D serum level exceeds 100 ng/ml. Although the results of high power studies are not available, correcting vitamin D status seems plausible in all MS and CIS patients. Maintaining the serum 25(OH)D level between 40 and 100 ng/ml is not known to exert adverse effect. More ever, it might be associated with lower disease activity.

Effects of atorvastatin on plasma matrix metalloproteinase-9 concentration after glial tumor resection; a randomized, double blind, placebo controlled trial.

BACKGROUND: Neurosurgical procedures such as craniotomy and brain tumor resection could potentially lead to unavoidable cerebral injuries. Matrix metalloproteinase-9 (MMP-9) is up-regulated in neurological injuries. Statins have been suggested to reduce MMP- 9 level and lead to neuroprotection. Atorvastatin preoperatively administered to evaluate its neuroprotective effects and outcome assessment in neurosurgical-induced brain injuries after glial tumor resection. In this prospective, randomized, double-blind, placebo-controlled trial, 42 patients undergoing glial tumor surgery randomly received 40 mg atorvastatin or placebo twice daily from seven days prior to operation and continued for a 3 weeks period. Plasma MMP-9 concentration measured 4 times, immediately before starting atorvastatin or placebo, immediately before surgery, 24 hours and two weeks after the surgery. Karnofsky performance score was assessed before first dose of atorvastatin as a baseline and 2 months after the surgery. RESULTS: Karnofsky performance scale after surgery raised significantly more in Atorvastatin group (11.43 +/- 10.62 vs. 4.00 +/- 8.21) (p = 0.03). Atorvastatin did not significantly reduce MMP-9 plasma concentration 24 hours after surgery in comparison to placebo. No statistical significance detected regarding length of hospital stay among the groups. Significant reduction in MMP-9 plasma concentration was recorded in atorvastatin group two weeks after surgery (p = 0.048). CONCLUSIONS: Significant statistical differences detected with atorvastatin group regarding MMP-9 plasma concentration, clinical outcome and Karnofsky performance score. Consequently, atorvastatin use may lead to better outcome after neurosurgical procedures.

Using Modern Learning Method to Teach Pharmacy Students Psychopharmacotherapy.

Background: Applying modern educational methods for digital native students seems necessary. Active learning strategies promote students' skills and knowledge. This study was conducted to design and evaluate active learning methods by teaching psychopharmacotherapy to pharmacy students. Methods: This was a quasi-experimental study with three randomized study groups (control, game, and multimedia), using a pre-and post-test design, conducted on 155 students of 5-year pharmacy in 2022 at the Faculty of Pharmacy of Tehran University of Medical Sciences, Iran. Overall, 18 clinical cases were designed for the basic structure of interventions. After teaching psychopharmacotherapy contents through lecturing, the pre-test was held. The next steps were playing the educational game, studying the multimedia case-based learning files, and then completing questionnaires, respectively. Then, a post-test was held. Results: 65.33% of participants were female and 34.66% were male. The pre-test and post-test scores comparison showed no difference in control group (P=0.409). However, in the serious game and multimedia groups, the average score of pre-test and post-test had a statistically significant difference (P<0.001, P=0.002 respectively), this difference was higher in the serious game group. Questionnaire evaluation showed substantial differences between game and multimedia groups. Conclusion: The educational interventions were able to improve student's knowledge and skills so they can better help patients and promote public health. In the sections of Confidence, Social Interactions, Fun, Focused attention, Learnability, Relevance, and Perceived Learning, the serious game far outweighed the multimedia case-based learning.

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 Multiple Sclerosis Disease-modifying Drugs.

Introduction: High frequency of adverse drug reactions (ADRs) challenges multiple sclerosis (MS) treatment. This study aims to assess the nature and frequency of ADRs induced by MS medications in an observational cross-sectional study. Methods: ADRs of all outpatients who had seen a neurologist and had received at least one disease-modifying therapy (DMT) for MS during the last three months were investigated. Results: A total of 484 ADRs were detected in these patients. The preventability rate was 5.9%, and 0.61% of reactions were serious. Conclusion: The high frequency of adverse drug reactions in this study shows a strong need for strategy planning to increase patients' adherence to treatment. Highlights: Adverse drug reactions (ADRs) are common in MS patients using disease modifying therapies.Such ADRs are more common in women than men.Various brand names of biosimilar disease-modifying therapy (DMT)s may have a different ADR profile. Plain Language Summary: Multiple sclerosis (MS) is a condition that can be managed by using disease modifying medications. Such medication could trigger an adverse reaction in the patients., affecting their commitment to the treatment. By identifying these adverse reactions and educating the MS patients about these reactions and how the adverse effects can be managed, healthcare providers can improve the treatment process. This study recorded the adverse drug reactions in 250 MS patients who were receiving the medication for at least three months. Most of the patients (76.4%) experienced some kind of adverse reaction. A bigger proportion of women experienced adverse reactions than men. About 84% of these reactions occurred within the first 3 hours of receiving the medication. Depending on the medication's brand name, the rate of adverse drug reactions were different in some cases. The results of this study point out the fact that experiencing adverse drug reactions is common in MS patients and these experiences could be different for each medication with a different brand name. Therefore, it is important for the healthcare providers to inform the patients about such reactions and the patients should seek all the information they need to manage these adverse effects by consulting their physician.

Ginkgo biloba Efficacy in the Treatment of Drug-Induced Parkinsonism: A Randomized Clinical Trial.

Background: Drug-induced parkinsonism (DIP) is one of the most common movement disorders in approximately 20 - 35% of patients on antipsychotic medications. Managing the symptoms of DIP is challenging due to the limited number of potentially effective medications. On the other hand, this restricted possible treatment could have numerous side effects that ultimately result in patients stopping the medication all at once. The neuroprotective property of Ginkgo biloba extract (EGb) emerged as an effective commodity for the additional treatment of psychiatric disorders. Objectives: This study aimed to evaluate the efficacy of EGb in psychiatric patients with symptoms of DIP. Methods: A sample of 63 patients who met the inclusion criteria were recruited and randomly assigned to control and experimental groups. Both groups were followed for 3 months. One group received 80 mg of G. biloba three times a day, and the control group received a placebo. The patients were evaluated using the Unified Parkinson's Disease Rating Scale and Montreal Cognitive Assessment. Results: Ginkgo could change the intensity of rest tremors, the severity of motor symptoms, rigidity, and bradykinesia. Ginkgo biloba might alleviate the severity of parkinsonism and motor symptoms and could lead to changes in the two components of working memory and short-term memory. Conclusions: Ginkgo biloba extract can be used as an effective and safe treatment in the management of DIP, whether in patients diagnosed with psychotic disorders or mood disorders.

Relationship Between Psychological Impacts of COVID-19 and Loneliness in Patients With Dementia: A Cross-Sectional Study From Iran.

Objectives: Although the COVID-19 pandemic has affected people all around the world, the elderly is at a higher risk of suffering from its consequences. One of the serious concerns is developing loneliness and post-traumatic stress symptoms, which may contribute to cognitive decline at older ages. This study aimed to examine the psychological responses and loneliness in elderly patients diagnosed with dementia. Methods: Twenty-one patients diagnosed with dementia, with ages older than 40, and 19 caregivers were enrolled in the study. The patients have undergone a comprehensive neuropsychiatric interview and were assessed with De Jong Gierveld Scale for loneliness and Impact of Event Scale-Revised (IES-R). The severity of dementia was assessed by Functional Assessment Staging Tool (FAST Scale) and the Montreal Cognitive Assessment (MoCA). Results: No significant difference was seen in patients and caregivers in the IES-R and loneliness scales. A higher level of avoidance and social and total loneliness were seen in higher FAST levels (p-value: 0.046). There was a negatively significant correlation between MoCA score and avoidance. Hyperarousal was significantly correlated with emotional loneliness in patients. Conclusion: We found a direct relationship between cognitive decline and the psychological impacts of COVID-19. Our results highlight the need for more comprehensive studies to further investigate the influence of the pandemic on the worsening of cognitive impairment and loneliness in patients with dementia.

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.

Evaluation of the Effectiveness of an Herbal Formulation of Boswellia sacra Flueck. In Improving Cognitive and Behavioral Symptoms in Patients with Cognitive Impairment and Alzheimer's Disease.

Objective: This study aimed to assess the efficacy of an herbal formulation based on Boswellia sacra in improving cognitive and behavioral symptoms in patients with mild cognitive impairment (MCI) and mild-to-moderate stages of Alzheimer's disease (AD). Methods: A 3-month, parallel-group, placebo-controlled trial was implemented from October 2021 to April 2022. Patients with MCI and mild-to-moderate stages of AD aged above 50 years (n = 60; 40 women, 20 men) enrolled in the study using clinical diagnosis and a score of 10-30 on the mini-mental state examination (MMSE) test. They were assigned into two groups; one receiving a herbal formulation) include B. sacra, Melissa officinalis, Piper longum, Cinnamomum verum, and Physalis alkekengi) three times a day and the other receiving a placebo for 3 months. The main efficacy measures were the changes in cognitive domains based on the MMSE and changes in behavioral and psychiatric symptoms based on neuropsychiatric inventory (NPI) scores compared with baseline. Side effects were also recorded. Findings: Results of this study showed significant differences between the two groups after 3 months in terms of all the assessed variables, including the overall result of the mean score of MMSE and NPI tests (P ≤ 0.001). The herbal formulation had the most considerable effects on the domains of orientation, attention, working memory, delay recall, and language of the MMSE test. Conclusion: Herbal formulation based on B. sacra was significantly effective compared to a placebo in improving cognitive and behavioral symptoms in patients with MCI and mild-to-moderate AD.

Adverse drug reactions induced by cardiovascular drugs in cardiovascular care unit patients.

PURPOSE: To detect the type, rate, seriousness, and preventability of adverse drug reactions (ADRs) attributable to cardiovascular drugs in cardiovascular care unit; and to determine the relationship between patient factors and detected ADRs. METHODS: Patients admitted to cardiovascular care units in Tehran Heart Center over an eight month period who received at least one cardiovascular drug were eligible to enter the study. ADRs were recorded based on information collected by interviewing patients, reviewing patients' charts, laboratory test monitoring, and confirmation by physicians. The World Health Organization definition for ADR, its seriousness and casualty criteria, was used to evaluate the reactions. The preventability was estimated based on Schumock and Thornton questioning. The relationship between possible risk factors and ADRs occurrence were assessed by statistical analysis. RESULTS: During the study period, 677 patients entered the study. A total number of 189 ADRs were registered of which 22.2% were serious. The highest ADR rates were observed with Streptokinase (59.3%). The rate of preventable ADRs was 6.9%. Multivariate logistic regression analysis showed that patients with lower weight (OR = 0.95, 95%CI: 0.9-0.99) and patients with smoking history who had concurrent diseases (OR = 8.72, 95%CI: 1.53-49.52) had a higher risk of experiencing ADRs. CONCLUSION: The rate of ADRs induced by cardiovascular drugs in this study was 24.2%. This study has shown that anti-arrhythmic and thrombolytic agents need more attention.

Thiamine for Prevention of Postoperative Delirium in Patients Undergoing Gastrointestinal Surgery: A Randomized Clinical Trial.

OBJECTIVE: Postoperative delirium is a common complication after gastrointestinal surgery that is associated with adverse outcomes. Thiamine is an essential cofactor for the glycolysis, oxidative metabolism, production of neurotransmitters in the crebs cycle. In this study, efficacy of thiamine was assessed as a preventive strategy of delirium in patients undergoing gastrointestinal surgery. METHODS: In this randomized clinical trial, 96 adult patients admitted to the intensive care unit (ICU) following gastrointestinal surgery were included. Patients were allocated to receive either 200 mg intravenous thiamine daily or an equal volume of 0.9% saline for 3 days. Delirium was evaluated twice daily based on the confusion assessment method-ICU. The incidence of postoperative delirium was considered as the primary outcome, and total analgesic use and ventilation days has been defined as secondary outcomes of the study. FINDINGS: The incidence rate of delirium was significantly lower in the thiamine group than the placebo group on the first day (8.3% vs. 25%; Odds ratio: 0.27 [95% confidence interval (CI): 0.08-0.92]; P= 0.026) and on the second day (4.2% vs. 20.8%; or: 0.16 [95% CI: 0.03-0.81]; P= 0.014). No adverse effect related to thiamine was detected during the study course. CONCLUSION: Study results suggest that thiamine is a safe option for the prevention of postoperative delirium in patients after gastrointestinal surgery.

Drug Interactions of Psychiatric and COVID-19 Medications.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has become a pandemic with 1771514 cases identified in the world and 70029 cases in Iran until April 12, 2020. The co-prescription of psychotropics with COVID-19 medication is not uncommon. Healthcare providers should be familiar with many Potential Drug-Drug Interactions (DDIs) between COVID-19 therapeutic agents and psychotropic drugs based on cytochrome P450 metabolism. This review comprehensively summarizes the current literature on DDIs between antiretroviral drugs and chloroquine/hydroxychloroquine, and psychotropics, including antidepressants, antipsychotics, mood stabilizers, and anxiolytics. METHODS: Medical databases, including Google Scholar, PubMed, Web of Science, and Scopus were searched to identify studies in English with keywords related to psychiatric disorders, medications used in the treatment of psychiatric disorders and COVID-19 medications. RESULTS: There is a great potential for DDIs between psychiatric and COVID-19 medications ranging from interactions that are not clinically apparent (minor) to those that produce life-threatening adverse drug reactions, or loss of treatment efficacy. The majority of interactions are pharmacokinetic interactions via the cytochrome P450 enzyme system. CONCLUSION: DDIs are a major concern in the comorbidity of psychiatric disorders and COVID-19 infection resulting in the alteration of expected therapeutic outcomes. The risk of toxicity or lack of efficacy may occur due to a higher or lower plasma concentration of medications. However, psychiatric medication can be safely used in combination with COVID-19 pharmacotherapy with either a wise selection of medication with the least possibility of interaction or careful patient monitoring and management.

Role of dimethyl fumarate in the treatment of glioblastoma multiforme: A review article.

Glioblastoma multiforme (GBM), the most frequent malignant and aggressive primary brain tumor, is characterized by genetically unstable heterogeneous cells, diffused growth pattern, microvascular proliferation, and resistance to chemotherapy. Extensive investigations are being carried out to identify the molecular origin of resistance to chemo- and radio-therapy in GBM and find novel targets for therapy to improve overall survival rate. Dimethyl fumarate (DMF) has been shown to be a safe drug with limited short and long-term side effects, and fumaric acid esters (FAEs), including DMF, present both anti-oxidative and anti-inflammatory activity in different cell types and tissues. DMF has also anti-tumoral and neuroprotective effects and so it could be repurposed in the treatment of this invasive tumor in the future. Here, we have reviewed DMF pharmacokinetics and different mechanisms by which DMF could have therapeutic effects on GBM.

Adverse drug events leading to emergency department visits at an eye hospital: A brief report.

PURPOSE: To evaluate adverse drug events (ADEs) resulting in emergency department visits in an eye hospital. METHOD: Emergency department visits at Farabi Eye Hospital were assessed for a 7-day period. The patients' eye disorders and drug history were evaluated to detect ADEs. RESULTS: Of 1631 emergency visits, 5 (0.3%, 95% CI: 0.13-0.71%) were drug related. Tetracaine eye drops accounted for 4 (80%, 95% CI: 38-96%) cases with corneal involvement. The other case was an intense conjunctival injection due to naphazoline eye drops. CONCLUSION: ADEs should be considered in differential diagnosis of ocular emergency problems and preventive measure should be considered.

Costs of Hospital Admission on Primary Immunodeficiency Diseases.

BACKGROUND: Primary immunodeficiency diseases (PID) are heterogeneous group of inherited disorders mainly characterized by recurrent infections leading to several times hospital admissions. The economic impact of PID is a challenging issue; therefore, this study was designed to determine the medical costs of hospitalizations in this group of patients as an indicator of the direct cost of these diseases. METHODS: One hundred and ten children with PID hospitalized in the Children's Medical Center Hospital, Tehran, Iran were included in this study during Jan 2011 and Jan 2012. All direct costs during the admission period were calculated, using the hospital information system. RESULTS: Medical cost was 7.090$ per patient per admission. Among them, about 1.580$ belong to drug consuming during hospitalization. Anti-infective drugs for systemic use were the most cost-consuming group of drugs, followed by alimentary tract and metabolism and blood and blood forming organs agents. Investigation of anti-infective group internally showed that immune sera and immunoglobulin and antiviral agents for systemic use consisting the most important medication for PID patients during hospital admission. CONCLUSION: Although the results of economic evaluations in a region cannot necessarily be applied to other regions, having an overall estimation of hospital admission costs and types of drugs used during admission could be helpful in health policy system.

Conjugated Estrogen in Late-Onset Hemorrhagic Cystitis Associated with Hematopoietic Stem Cell Transplantation.

Background: Hemorrhagic cystitis (HC) is one of the most challenging complications in hematopoietic stem cell transplantation (HSCT). Estrogen is one of the suggested treatments for controlling this problem. Subjects and Methods: We performed a randomized case-control study to evaluate the efficacy of oral conjugated estrogen on HC management in 56 HSCT patients. Patients were randomly assigned to the drug group (received 6.25 mg conjugated estrogen oral tablets in a daily single dose during hematuria period) or control group. Results: The median time to complete response was 36 and 24 days in the drug and control group, respectively. The median time of down stage was 24 days in the drug group and 12 days in control group. Adjusted for HC grades, the relative risk of complete response for patients in control group was 1.613 times more than that of patients in drug group; nevertheless, not significant (p=0.122). Conclusion: Our study did not show any benefit in use of oral conjugated estrogen in the management of HC.