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HbF induction is an appropriate strategy to ameliorate the severity of β-thalassemia symptoms. Hydroxyurea (HU) is the most common chemical agent introduced as an HbF inducer but responsiveness to HU is variable and the introduction of HbF inducers alternative to HU with low cytotoxicity has been a crucial challenge. Resveratrol is an HbF inducer agent that may have favorable effects on the differentiation of hematopoietic erythroid progenitors (HEPs). The present study aimed to investigate the effect of resveratrol on γ-globin, stress response, and anti-apoptotic gene expression among hydroxyurea (HU)-responders and HU-nonresponders (HU-NR). Four cases of HU-R and four cases of HU-NR were studied. HEPs of the patients were cultured, and the expression of γ-globin, Foxo3, and Bclxl was assessed. Moreover, the differentiation and apoptotic rate of the cells were investigated using flow cytometry analysis. In three cases, the γ-globin gene expression increased after resveratrol treatment. All of the HU-NR patients were also non-responders to resveratrol (Res-NR). The expression of Foxo3 and Bclxl genes was higher in responders to resveratrol (Res-R) compared to non-responders (Res-NR). The rate of apoptosis in Res-R patients was also lower than in Res-NR. Responders to resveratrol also had a higher rate of HEP maturation. The cells of both HU–NR and Res-NR patients could not adapt to stress conditions and proceed to the erythroid differentiation. In conclusion, resveratrol increased the γ-globin expression in HEPs of β-thalassemia patients. The response was observed only in R-HU patients with similar cellular pathways.

Background and purpose: Today, ensuring food security for the inhabitants of the earth, and preserving agricultural production from destruction due to drought, pests, and diseases, seems more necessary than ever. Farmers across the world are forced to use various pesticides to combat factors that reduce production, but these toxins not only remain on the surface of the products but also penetrate the tissues of fruits, vegetables, and even grains. Although washing fruits or peeling them can be effective in reducing surface contamination of pesticides, removing their toxic effects from the internal tissues of fruits is almost impossible. In such a way most agricultural products that have been exposed to pesticides and are presented to the market shortly after spraying contain pesticide residues. Although the use of pesticides and chemical fertilizers in modern agriculture significantly increases agricultural products, it should be noted that excessive use of pesticides in agricultural production leads to higher levels of pesticide residues in agricultural products exceeding the Maximum Residue Limit, which is considered a risk factor for human health and environmental pollution. The negative effects of chemical toxins on health include various types of cancers, neurological diseases, diabetes, respiratory diseases, failures, fetal diseases, genetic problems, and harmful effects on the environment such as pest resistance, their dominance, and the disappearance of beneficial insects. Considering that citrus fruits are considered a strategic product in Mazandaran province, this research was conducted to investigate the level of pesticide residues in citrus orchards in Sari County. Materials and methods: The residues of pesticides in the citrus fruits produced in Sari county were investigated in areas monitored by the Agricultural Jihad Organization, the Agricultural Research Center, and Natural Resources of Mazandaran province, to control the type, method of pesticide use, and observing the withholding period. In this study, 15 oranges fruit samples were examined. Each sample was approximately 1 kilogram of each product, which was transferred to the food control laboratory of Mazandaran University of Medical Sciences at a temperature of 4 degrees Celsius. The samples were prepared using the QuEChERS method. The consumption and residue levels of pesticides were identified using the GC-MS method. The Food and Drug Organization and the National Standard Organization of Iran (ISIRI) declared 200 types of pesticides as the most commonly used pesticides in citrus orchards, which were evaluated for their residues in this research. Results: Totally, 3 types of pesticides including Chlorpyrifos, Ethion (Class II), and Pyriproxyfen (Class U) were identified, with Chlorpyrifos being the most commonly used. None of the identified pesticides belonged to Class Ia or Class Ib. Among the identified pesticides, the residue of Ethion exceeded the Maximum Residue Limit (MRL) set by ISIRI. Conclusion: Given the role of pesticides in food safety and environmental pollution, efforts to reduce the use of pest control poisons to minimize the risk to human health and the environment remain challenging and a valuable goal. Although monitoring of production by executive organizations has led to a significant reduction in pesticide consumption, in some cases, residues higher than the permissible limit are still observed. Also, it should be noted that pesticide residues can become environmental pollutants by entering the soil and water. Therefore, along with increasing farmers' awareness, the expansion, substitution, and implementation of Integrated Pest Management (IPM) are still significant for environmental preservation and cost reduction.

Background and purpose: The employment of pesticides for the prevention, elimination, and reduction of pests detrimental to agricultural products throughout various stages of crop cultivation is essential for improving the health of these products; nevertheless, pests remain a critical factor in the degradation and destruction of agricultural goods, posing a threat to food security. Even though the deployment of pesticides and chemical fertilizers in modern agricultural practices considerably boosts agricultural output. However, it should be noted that excessive and inappropriate use of pesticides in agricultural product production and failure to consider factors affecting their residue levels can result in pesticide residues in these products exceeding the maximum allowable limit set by national and international standards (Maximum Residue Limit), which is considered a risk factor for human health and environmental pollution. Due to the increasingly widespread use of pesticides in agriculture, this issue has become a significant topic in food safety. Despite various methods being used to assess the potential risks of pesticides to human health and the environment and to control their consumption, efforts to reduce the use of pest control poisons to minimize the risk to human health and the environment remain challenging and a valuable goal. Additionally, since rice is considered a major source of energy supply, studying pesticide residues in rice to protect consumer health is always significant. As this product is considered a strategic product in Mazandaran province, this research was conducted to examine the level of pesticide residues in rice produced in Mazandaran province. Materials and methods: In the cross-sectional residues of pesticides in the rice produced in Sari County in areas where the type, and method of pesticide use are monitored by the Agricultural Jihad Organization, the Agricultural Research Center, and Natural Resources of Mazandaran Province were investigated. In this study, 15 samples of rice were examined. Each sample of about 1 kilogram of each product was transferred to the Food Control Laboratory of Mazandaran University of Medical Sciences at a temperature of 4 degrees Celsius, and the consumption and residue levels of consumed toxins were identified using the GC-MS method. 200 types of pesticides, which were recognized as authorized and unauthorized pesticides for use in rice according to the national monitoring report of the Food and Drug Organization and ISIRI, were selected and their residues were evaluated. Results: The analysis results of 15 samples of rice from monitored areas in Sari County showed that none of the 200 types of authorized and unauthorized pesticides had any residue in the products under investigation. Conclusion: Although no pesticide residues were observed in the present study, it should be noted that pesticide residues in the bran of the samples under investigation were not evaluated. Considering that bran enters the human food chain through animal feed, controlled pesticide consumption can still have indirect effects on human health and food intake. Also, in the cultivation of the above products, pesticides have been used, which in controlled amounts can contaminate soil and water. Given the emphasis on reducing pesticide consumption and replacing it with Integrated Crop Management (ICM) methods, the goal of this research and practitioners is to continue to educate and support farmers to move towards ICM in the next stages, taking a higher step toward human health, environmental preservation, and reducing costs associated with pesticide use.

Background and aim: We conducted a review to determine the efficacy of amlodipine alongside iron chelators on serum ferritin levels and liver T2-weighted magnetic resonance imaging (MRI T2*) in β-thalassemia patients. Methods: Systematic search was conducted in multiple databases, including Web of Science, PubMed, Scopus, Embase, Cochrane Library, ClinicalTrials.gov, the Iranian Registry of Clinical Trials (IRCT), ProQuest, OpenGrey, and Web of Science Conference Proceedings Citation Index. The search was closed in January 2023. Primary outcomes were comprised of liver MRI T2* (millisecond (msec)) and serum ferritin levels (ng/mL). Results: Seven studies (n = 227) were included in the study. The pooled Cohen’s d for serum ferritin was estimated at −0.46, 95% confidence interval (CI) −1.11 to 0.19 and p = 0.16 (I2 86.23%, p < 0.0001). The pooled mean difference for serum ferritin was −366.44 ng/mL, 95% CI −844.94 to 112.05, and p = 0.13 (I2 81.63%, p < 0.0001). After a meta-regression based on the length of using amlodipine, a coefficient for the mean difference was also −23.23 ng/mL and 95% CI −155.21 to 108.75. The coefficient obtained from a meta-regression as per the amlodipine dose at 5 mg/day than 2.5 to 5 mg/day anchored at −323.49 ng/mL and 95% CI −826.14 to 1473.12. A meta-regression according to the baseline values of serum ferritin discovered a coefficient of 1.25 ng/mL and 95% CI 0.15 to 2.35. Based on two included studies (n = 96), the overall Cohen’s d for liver MRI T2* was 2.069, 95% CI −0.896 to 5.035, and p = 0.17 (I2 96.31%, p< 0.0001). The synthesized mean difference for liver MRI T2* was 8.76 msec, 95% CI −4.16 to 21.67, and p = 0.18 (I2 98.38%, p < 0.000). Conclusion: At a very low level of evidence, probably using amlodipine at a dose of 2.5 to 5 mg a day, up to a year, alongside iron chelators slightly decreases serum ferritin levels in iron-overloaded thalassemia cases by nearly 366 ng/mL (23 ng/mL per month). The liver MRI T2* might also rise to 8.76 msec upon co-therapy with amlodipine.

Background and purpose: Given the inevitable use of metformin in treatment, the management and possible elevation of cobalamin levels by metformin use should be addressed. However, the reduction in vitamin B12 levels caused by metformin has been mentioned in many studies and books, but there is no suggestion for the concomitant use of vitamin B12 with metformin. This study was conducted with the aim of assessing the association between metformin use and vitamin B12 depletion in type 2 patients Materials and methods: In this descriptive cross-sectional study, 96 people were randomly selected. Two clinic patients referred to Tankab Hospitals and Imam Sajjad (AS) Ramsar Hospital internal clinic with normal CBC from the beginningwere included in this study. Information was recorded in patient records through paraclinics and interviews. 5 ml of venous blood samples was drawn these patients who had been taking metformin for at least 6 months to determine hemoglobin levels, red blood cell indices including MCV, and vitamin B12 levels. CBC and B12 plasma level were taken.t-tests and analysis of variance, Mann-Whitney and Kruskal-Wallis tests, chi-square tests and logistic regression were used. The software used in this study is IBM-SPSS V.20, and the significance level of the tests is considered to be less than 5%. Results: In this study, 96 patients were examined. The differences in vitamin B12 levels in diabetic patients taking metformin were borderline significant depending on age (P=0.063). The vitamin B12 level was significantly higher in men than in female patients (P=0.023). There were no statistically significant differences in vitamin B12 levels depending on BMI, Hb level, underlying disease and use of other hypoglycaemic medication (P>0.05). The frequency of vitamin B12 level was significantly lower in diabetic patients taking metformin with normal MCV than in patients with MCV (P=0.012). The frequency of vitamin B12 level was highestin diabetic patients taking 2000 mg metformin per day (13.3%) and lowest in patients taking 500 mg per day, and this difference was statistically significant (P=0.013). Conclusion: The results show that metformin causes a decrease in vitamin B12 levels in diabetics who take it. Due to the high prevalence of vitamin B12 deficiency caused by metformin and its relationship with dose and duration of use, patients ' serum levels of vitamin B12 should be monitored regularly and, in case of deficiency or symptoms of deficiency, patients should take vitamin B12 supplements to improve the quality of treatment and prevent complications caused by diabetes and metformin.

Background: Complex interplays happen in absorption and function of iron, zinc and copper. Both zinc deficiency and excess may lead to anemia. In Iran, commonly available supplements for chronic kidney disease (CKD) patients contain 25 mg-zinc (Zn). This study compared 25 mg versus 7.5 mg dose of zinc in anemia of CKD patients, the latter dose approximates to recommended dietary intake (RDI) of zinc. Methods: In this double-blinded clinical trial, 51 non-dialysis CKD patients were randomized to continue previous formulation (25 mg-Zn group) or change to a new preparation (7.5 mg-Zn group) for three months. Blood counts and serum iron, zinc and copper status were compared between and within the groups. Results: At the end of the study, serum copper and ceruloplasmin concentrations were significantly higher in 7.5 mg-Zn group compared with those in 25 mg-Zn arm (115.04± 23.05 vs. 102.48±14.98 µg/dL; P= 0.02 and 29.97±7.94 vs. 25.42±4.23 mg/dL; P= 0.01, respectively). Serum zinc levels did not differ between two groups (76.73±15.35 vs. 77.68±18.07 µg/dL for 7.5 mg-Zn and 25 mg-Zn groups, respectively; P= 0.84). After three months, patients in 7.5 mg-Zn group experienced increase in their Hb (11.11±1.17 vs. 10.72±1.03 g/dL; P= 0.04), HCT (35.28± 4.01 vs. 33.96± 3.74%; P= 0.03), MCV (86.30 (81.40-90.82) vs. 86.00 (80.35-88.77) ¦L; P= 0.01) and ferritin (202.60 (79.29-298.97) vs. 129.07 (42.25-225.87) ng/mL; P

Background: According to COVID-19 mutation and no defined treatment, it is necessary to find effective treatment. Chlorpromazine, a phenothiazine antipsychotic drug, has been shown in animal studies to have antiviral effects by inhibiting clathrin-mediated endocytosis. The aim of this study was to evaluate the effectiveness of adding chlorpromazine to the atazanavir/ritonavir regimen in the treatment of moderate COVID-19 patients. Methods: In this randomized double-blind clinical trial, sixty hospitalized patients with moderate COVID-19 confirmed by CT findings or polymerase chain reaction (PCR) were enrolled. All patients received atazanavir/ritonavir 300mg/100mg once daily. In two parallel groups, chlorpromazine 25 mg three times a day or a placebo was administered for up to 14 days. Complete blood count with differential, C-reactive protein (CRP), liver enzymes, and erythrocyte sedimentation rate was measured on days 1, 3, 5, 7, and 10. The primary outcome was the improvement of oxygen saturation and the secondary outcome was the duration of hospitalization and conversion of PCR test results. Results: Oxygen saturation during the hospitalization was not different among the two groups. The mean duration of hospitalization in the chlorpromazine group was 7.4±2.7 days and in the placebo was 8.2±3 days (P=0.2). Compared to baseline, both groups showed an increase in white blood cell count (P=0.04) and polymorphonuclear cells (P=0.04) but lymphocyte count decreased. At the end of the study, the PCR test was negative in 100% of patients in the chlorpromazine group and 95% of patients in the placebo group. Conclusion: In adult hospitalized patients with moderate symptomatic COVID-19, adding chlorpromazine to the atazanavir/ritonavir regimen did not improve outcomes.

Consumption of thousands of tons of industrial chemicals in agriculture, such as chemical fertilizers and pesticides, has created significant environmental problems. The regulations for the import, production, formulation, and utilization of chemical, biological and organic fertilizers and pesticides are not completely implemented in Iran. According to the latest notification of the Jihad Agriculture Minister entitled "Instructions for monitoring the production and health promotion of plant products" (1095/020-06/04/2022), the Ministry of Health is the body responsible for investigating and monitoring the remaining of chemical compounds (pesticides, fertilizers, growth regulators, plant hormones, nitrates, and heavy metals). Mazandaran University of Medical Sciences Food and Drug Deputy in collaboration with Research and Technology Deputy, The Health of Plant and Livestock Products Research Center, Babol University of Medical Sciences Food and Drug Organization, Provincial Agricultural Jihad Organization, Provincial Agricultural and Natural Resources Research Center, Agricultural and Natural Resources Engineering Organization of Iran, Iran National Standards Organization, and Environment Protection Agency aim at regulating the utilization of chemical pesticides in agricultural products (strategic products) in Mazandaran province to control the consumption of pesticides in agricultural products and minimize their potential risk to human health and the environment. The main solutions include generating QR Code in the integrated electronic services system of the Organization of Agricultural Engineering and Natural Resources and issuing certificates for product improvement in the Electronic Agricultural Permits System in order to register plant products in production units.

Background: Drug use evaluation studies are conducted to assess the pattern of prescribing and administration of a drug. Deep vein thrombosis is one of the most important clinical issues around the world. This study examined the pattern of enoxaparin consumption, one of the most widely used anticoagulants, for the prevention and treatment of thrombosis in a non-teaching hospital. Methods: In this cross-sectional prospective study, 117 patients receiving enoxaparin in different wards of Imam Sajjad Hospital in Ramsar, Iran, were studied. Data on how to prescribe and use enoxaparin were recorded in a questionnaire designed according to UpToDate recommendations. Demographic variables, prophylaxis, and therapeutic indications, prophylaxis and treatment doses, interval, and monitoring information were evaluated. Finally, the results were compared with UpToDate suggestions. Results: The mean age of patients was 68.9 years, and 52.1% were men. Enoxaparin was prescribed for 35.9% of patients as prophylaxis, and 64.1% received this drug for treatment. Overall, prophylactic doses were inappropriately administered in 41.5% of patients. Improper therapeutic doses were also prescribed for 52% of subjects. Conclusion: The results of this study showed that the dosage and interval of enoxaparin administration were significantly inappropriate. It seems the prescribers must have more adherence to the valid and reliable enoxaparin guidelines for more rational practices.

Background: The northern coastal regions of Iran are endemic for leptospirosis which may range from a subclinical illness to a progressively fatal disease. There has been growing evidence that inflammatory markers play a significant role in the severity and prognosis of leptospirosis. This study aimed to investigate inflammatory cytokines in patients with leptospirosis. Methods: This descriptive-analytical prospective study was performed in 75 patients over 18 years old who had a positive microscopic agglutination test (MAT) titer from January to June 2019. SPSS software Version 20 was used for statistical analysis and the significance level was considered as p

Abstract Background Leiomyosarcoma (LMS) is an aggressive soft tissue sarcoma that is derived from smooth muscles. Ifosfamide is in use for advanced metastatic LMS. Case A‐44‐years old woman with a chief complaint of pain in the epigastric area, itching, coughing, nausea, and vomiting was referred to the emergency department. Her medical history was LMS. She had taken Ifosfamide and mesna in her last chemotherapy. Seventy percent of her liver and her left kidney were removed 4 years ago to prevent the progress of the disease. Because of the increase in the level of creatinine and urea in the initial laboratory report, a Shaldon catheter was inserted for the patient, and she was under emergency dialysis for 3 h. In addition, during the six‐day hospitalization period, dialysis was done two times. Finally, the patient was discharged with improved clinical tests accompanied by a twice‐weekly dialysis order. Conclusion Ifosfamide is metabolized into chloroacetaldehyde, which can cause acute kidney injury. Recovery from acute kidney injury may not always be perfect and can lead to some degree of chronic kidney disease. Opposite to hemorrhagic cystitis, mesna is not effective in preventing ifosfamide's nephrotoxicity and N‐acetylcysteine may be effective in the prevention of this nephrotoxicity.

Background: Proton Pump Inhibitors (PPIs) are the most common medicine for the treatment and prophylaxis of acid peptic conditions. The inappropriate use of the PPIs, mainly the intravenous form of pantoprazole may lead to excessive cost and unexpected adverse effects. Objectives: The present study aimed to evaluate the use of intravenous pantoprazole in the International Heart Center in the north of Iran. Methods: The current retrospective study was performed on 215 patients hospitalized in Fatemeh Zahra Hospital in Sari City, Iran. Patients’ demographics, the type and doses of pantoprazole, and other relevant clinical data were recorded from their documentation. The appropriate use of pantoprazole was evaluated according to recommendations provided by Medscape 2020, and UpToDate 2020. Results: Prescribing PPI was appropriate for 53.5% of the examined patients; however, the majority of intravenous prescription cases were inappropriate (76.7%). Oral PPIs could have been used in 93.5% of the cases; however, they received the parenteral form of pantoprazole. The main cause of pantoprazole prescription in the explored hospital was stress ulcer prophylaxis, with the median 4/18 days used, which internal specialists in most of the cases (45.6%) prescribed. Conclusion: In the current study, administrating intravenous pantoprazole was inappropriate in most of the cases. As a result of this improper administration, the extensive cost is exposed to the healthcare system, i.e., likely to be unsafe for patients. Accordingly, risk and indication evaluation for the prescription of pantoprazole should be a priority in each patient. Finally, it seems necessary to determine a protocol for PPI prescription per hospital for the rational use of drugs.

Background and purpose: This study aimed at evaluating utilization of imipenem and assessing the role of pharmacist in rational use of antibiotics. Materials and methods: A retrospective/prospective observational study was conducted in Ramsar Imam Sajjad Hospital in 59 patients receiving imipenem, 2018-2019. In retrospective phase, patients’ records were reviewed, while in prospective phase, a pharmacist provided recommendations on use of imipenem. Duration of taking imipenem, dosage, and dosage adjustment in renal insufficiency were compared with standard protocols. Results: Mean age of the patients was 69.89±16.12 years and there were 29 males. The most common reason for prescribing imipenem was lower respiratory tract infection (54%) which was more used in internal medicine ward (67.28%) ordered by infectious diseases specialist (65%). In retrospective and prospective phases, mean dosage of imipenem, duration of receiving the antibiotic, and dosage adjustment in renal insufficiency were according to standard protocols in 65% and 85%, 45% and 65%, and 60% and 90% of the cases, respectively (P

Background and purpose: Drug interactions are one of the serious subsets of medication errors and occur when the effects or toxicity of one drug are affected by another. This study aimed to investigate drug interactions and the role of pharmacist in reducing drug interactions in Ramsar Imam Sajjad Hospital, Iran. Materials and methods: This cross-sectional study was performed in all prescriptions of medicinal products by specialist physicians in Ramsar Special Clinic from March to May 2019. Drug interactions were determined based on Drug Interaction Facts (2014) and Drugs website (www.drugs.com). A list of drug interactions prescribed by each physician was compiled and discussed in face-to-face visits with physicians. They were then provided with a list of unsafe combinations of medications. Prescriptions of physicians who had previous history of prescriptions with drug interactions were reviewed within two months in January and February 2020. Results: In first phase, 2864 prescriptions were studied of which 268 (9.3%) were detected with drug interactions. There were 40 (14.9%) cases of major drug interactions and 228 (85%) cases of moderate drug interactions. After providing feedback to physicians about drug interactions, the rate of drug-drug interactions decreased from 9.3% to 6.4%. Conclusion: Many drug interactions are preventable and communications between physicians and pharmacists can help identifying drug interactions and minimizing their incidence.

In this report, we present a 29-year-old man who experienced EM five days after using sildenafil and tramadol. Based on clinical examination and history, the diagnosis of EM was made confirmed via skin biopsy, which found intra-epidermal bulla filled by fibrinous exudate, some mononuclear cells, and a few eosinophils. The spongiotic epidermis showed lichenoid interface dermatitis, eosinophilic spongiosis, and necrolysis, consistent with EM diagnosis. Fluocinolone, 0.025% ointment, was prescribed for the patient, and the lesions healed after two weeks of treatment.

Objective: To evaluate the utilization of the parenteral morphine in Emergency Department (ED) using the Anatomical Therapeutic Chemical Classification/Defined Daily Doses (ATC/DDD) system. Methods: In this retrospective cross-sectional study, morphine administration was recorded in 4-year time period from January 2013 to December 2016 in the ED of a referral center. The dose of the administered morphine was evaluated using the ATC/DDD system. The ATC/DDD of the parenteral morphine was calculated based on the world health organization (WHO). The data was evaluated based on the different diagnosis and conditions using the ATC/DDD protocol. Results: In this study, 500 patients referred to ED with mean age of 48.29 ± 10.10 years were included. There were 306 (61.2%) men and 194 (38.8%) women among the patients. The lowest and highest DDD of parenteral morphine were 0.1 and 0.43, respectively. The utilization of parenteral morphine was significantly higher in men when compared to women (pppp Conclusion: The utilization of parenteral morphine in the ED of our center was higher than the WHO standard dosage. The morphine utilization was associated with male gender, opium addiction and TCA consumption.

Background: Acute radiation proctitis (ARP) is a usual adverse effect in patients undergoing pelvic radiotherapy. The symptoms include diarrhea, rectal blood or mucus discharge, fecal urgency and tenesmus with pain. Sucralfate, an aluminum-based salt of sucrose octasulfate, is a cytoprotective agent that forms a coating barrier at injured sites by adhering to mucoproteins. It has been used in topical management of a wide variety of local lesion. This study was designed to evaluate the preventive effect of rectal sucralfate on acute radiotherapy induced proctitis. Methods: Seven percent sucralfate ointment was prepared for topical use. Drug quantification, chemical stability and microbial limit tests were performed carefully. In this randomized double blind placebo controlled trial, fifty-seven patients with pelvic malignancies undergoing radiotherapy were allocated to receive either 1 g of sucralfate or 1 g of placebo, given as a twice daily ointment, one day before and during radiotherapy for six weeks. The eligible patients were evaluated based on RTOG acute toxicity criteria and the following ARP symptoms weekly: rectal hemorrhage, diarrhea, rectal pain, and fecal urgency. The influence of symptoms on lifestyle were also recorded weekly. Results: Acute proctitis was significantly less prevalent in patients in the sucralfate group. The incidence of rectal bleeding (P=0.003), diarrhea (P= 0.002), rectal pain (P=

Abstract Background 5-Fluorouracil (5-FU) and capecitabine are fluoropyrimidine derivatives that mainly metabolized with dihydropyrimidine dehydrogenase enzyme (DPD). The genetic polymorphism in the genes encoding this enzyme may result in a decrease or loss of enzyme activity which may lead to the accumulation of medicines, their metabolites and potential toxicity. Method This cross-sectional study was conducted on 88 participants with colorectal cancer (CRC). After DNA extraction, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to determine the DPD gene (DPYD) polymorphisms including IVS 14 + 1 G > A, 2846 A > T and 2194 G > A. Chemotherapy-induced side effects were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE Version 5.0). Result Data were collected from 227 chemotherapy cycles of 88 patients with CRC. In a comparison of FOLFOX and FOLFIRI regimens, there was no significant difference in the occurrence of chemotherapy-induced diarrhea, nausea, vomiting and oral mucositis. However, the peripheral neuropathy was more frequent in patients who were treated with FOLFOX (P A polymorphism was observed in four patients (5.5%). There was no association between IVS14 + 1 G > A polymorphism and the occurrence of adverse reactions. Conclusion FOLFOX and FOLFIRI were the most common regimens in CRC patients and their toxicity profile was different in some adverse reactions. Prevalence of IVS14 + 1G > A variant was relatively higher than other similar studies. Trial registration Approval code; IR.MAZUMS.REC.95.2480 .

Abstract Background Acute radiation-induced proctitis (ARP) is the most common side effect following radiotherapy for malignant pelvic disease. This study evaluated the efficacy of Aloe vera ointment in prevention of ARP. Methods Forty-two patients receiving external-beam radiotherapy (RT) for pelvic malignancies were randomized to receive either Aloe vera 3% or placebo topical ointment during radiotherapy for 6 weeks. These patients were evaluated based on the severity (grade 0–4) of the following symptoms weekly: rectal bleeding, abdominal/rectal pain, diarrhea, or fecal urgency. RTOG acute toxicity criteria and psychosocial status of the patients were also recorded weekly. Lifestyle impact of the symptoms, and quantitative measurement of C-reactive protein (CRP), an indicator of systemic inflammation, were also measured. Results The results of present study demonstrated a significant preventive effect for Aloe vera in occurrence of symptom index for diarrhea (p

Abstract Background and objectives Cancer-related fatigue (CRF) is one of the most prevalent complications experienced by cancer patients during and after the process of treatment. Despite conducting a lot of studies, there is no approved therapy to help manage CRF. This study aims to investigate the efficacy of bupropion on CRF. Materials and methods In this double-blind randomized placebo-controlled clinical trial, a total of 30 eligible cancer patients suffering from fatigue were randomly divided into two groups (15 patients in each group). Bupropion was administered 75 mg/day for the first three days and 150 mg/day (divided in two doses) till the end of the study at week 6. Fatigue as the primary outcome was measured by BFI (Brief Fatigue Inventory) and FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy) scales. Secondary outcomes included HADS (Hospital Anxiety and Depression Scale) and performance status (PS) measured by Karnofsky and ECOG (Eastern Cooperative Oncology Group) scales. Assessments were done at baseline, end of the second and sixth week. Results There was no significant difference between placebo and bupropion at baseline and the end of second week. Significant difference was seen between two groups at the end of week six (P = 0.006 based on BFI) in favor of bupropion. In-group assessment showed improvement in fatigue levels in both groups during study time (P = 0.000 based on BFI for both bupropion and placebo). Secondary outcomes (e.g., HADS and PS) were not different at baseline and the end of second week. However, at the end of week six, the difference was significant in favor of bupropion. Conclusion A six-week trial of bupropion reduces the CRF and improves the PS of cancer patients. Trial registration: Current Controlled Trials IRCT20090613002027N12, registration date: 2018-06-01.

Introduction: Glucose 6-Phosphate Dehydrogenase deficiency (G6PD) is an X-linked recessive disorder recognized as the most prevalent enzyme deficiency around the world. G6PD deficiency has a high prevalence in Iran, especially in the northern regions. As we know, hemolysis in G6PD patients was not reported with levofloxacin previously. Case Report: In this report, we introduce a 54-year-old G6PD deficient woman who experienced the symptoms of hemolytic anemia following completion of treatment with levofloxacin. Result: After ruling out other causes of hemolysis, by using the Naranjo scale, levofloxacin was considered as a possible cause of hemolysis. Conclusion: Though the hemolytic anemia induced by levofloxacin is extremely rare in G6PD deficient patients, drug-induced hemolytic anemia should be considered as one of the differential diagnoses. It would be appropriate to use an alternative antibiotic instead of levofloxacin in a G6PD deficient patient.

Backgrounds: There is no proven therapy for coronavirus disease 2019 (COVID-19) so far. The aim of this study was to evaluate the effect of interferon beta-1b combined with lopinavir/ritonavir and hydroxychloroquine in managing COVID-19.Methods: This is a non-randomized, open-label study on adult patients with moderate to severe COVID-19. The patients (≥ 18 years) received hydroxychloroquine 400 mg single dose, and lopinavir 400 mg/ritonavir 100 mg every 12 h (for 7-10 days) with or without subcutaneous interferon (IFN) beta-1b 250 mcg every other day for e primary outcome was clinical improvement in NEWS2 changes. Duration of hospital stay, mortality rate, and safety profile of therapeutic regimens were secondary outcomes.Results: Between March 20 and April 3, 2020, a total of 114 patients were recruited and 59 patients completed the study. The IFN group had a significant improvement in clinical symptoms due to a significant reduction in NEWS2 (83.3% (25) vs 48.3% (14), P= 0.004). The time to clinical response in the IFN group was shorter than the control group (7 (5-12) days vs 9.5 (7-18), P=0.037). The IFN group also showed a significantly lower rate of 28-day mortality (6.8% (2) vs 34.5% (10), P= 0.01) and a lower need for invasive ventilation (6.8% (2) vs 34.5 (10), P= 0.008). Although the duration of ICU stay was marginally shorter in the IFN group, the results were not significantly different between the two groups (P=0.06).Conclusion: IFN beta-1b could be a potential therapeutic option for patients with moderate to severe COVID-19.

Background and purpose: Decreasing the quality of life in cancer patients is an essential factor that influences their lives during the process of treatment and after that. A lot of studies have been done to evaluate the efficacy of medical agents on quality of life. In this study, we evaluate the efficacy of Bupropion as an antidepressant agent in quality of life of cancer patients. Materials and Methods: In this double-blind randomized placebo-controlled clinical trial, a total of 30 eligible cancer patients suffering from fatigue were randomly divided into two 15-individual groups of bupropion and placebo. Bupropion was administered 75 mg/day for the first three days and 150 mg/day (in two doses) till the end of the study for group bupropion. Quality of life was measured by EORCT-QLQ-C3 scale. Adverse effects were assessed based on NCI Common Terminology Criteria for Adverse Events. The study was six weeks long and assessments were done at baseline, second week and sixth week. Results: There was no significant difference in scores between placebo and bupropion at baseline and second week. While, significant difference was seen at the week six (P=0.005 for function, P=0.036 for symptoms and P

Objective: Dihydropyrimidine dehydrogenase (DPD), an enzyme translated by DPD gene (DPYD), has a critical role in the metabolism of 5-fluorouracil (5FU). In this study we aimed to investigate the frequency of the IVS14+1 G>A, 2194G>A, 2846 A>T mutations in the DPYD gene in colorectal cancer patients in north of Iran and their association with side effects of 5FU. Methods: Venous blood samples of 89 colorectal cancer patients were drawn. After the DNA extraction from nuclear cells, a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to detect the frequency of the IVS14+1 G>A and 2846 A>T mutations. Tetra-Primer ARMS PCR optimization method was used to detect the 2194 G>A mutation. Side effects were classified according to CTCAE (common terminology criteria for adverse events V. 4) and the association between different polymorphisms and side effects were evaluated. Results: Of 89 colorectal patients, the frequency of IVS14+1 G>A and 2846 A>T polymorphism was 4 (5.1%) and 1 (1.1%), respectively. The 2194 G>A polymorphism was not detected. All 4 patients were heterozygous for IVS14+1 G>A mutation, whereas the only patient with 2846 A>T polymorphism was homozygous. Some adverse effects of 5FU including diarrhea, vomiting, mucositis and stomatitis were more frequent in patients with IVS14+1 G>A polymorphism. Conclusion: The prevalence of IVS14+1 G>A mutation in our patients were relatively high and was associated with a higher occurrence of 5FU-associated toxicities.

Background: The occurrence of drug–drug interactions (DDIs) and insufficient attention to medication reconciliation is one of the important challenges of pharmacotherapy in hospitalized patients. The aim of this study was to determine the extent of drug–drug interactions in patients based on medication reconciliation strategy. Methods: This descriptive cross-sectional study was performed for six months in patients admitted to Imam Reza Hospital in Amol, North of Iran. The data were obtained by using a medication reconciliation tool through a random sampling of patients admitted in Hospital wards from May 2014 until October 2014. A total of 200 patients were enrolled in the study. All patients had a history of medication use before admission. The drug interactions have been checked according to Drug Interaction Facts between newly prescribed drug and medication patient using before admission. The number and frequency of data were summarized by SPSS21 statistical software. Results: Major and Moderate DDIs were found in 7.5% and 64% of prescriptions. The most frequent DDIs were seen in those who were taking psychiatric drugs (33%) and cardiovascular drugs (30%). Most DDIs occurred among women over 60 years of age. The most frequently occurring DDIs was pharmacokinetics interaction between clopidogrel and atorvastatin (n=9). Other frequent interactions were between ceftriaxone and heparin (n=8) and metoprolol and insulin (n=3). Conclusion: This study showed a high rate of drug interactions and especially confirms the importance of medication reconciliation in providing a comprehensive drug history and exploring drug interactions.

Beginning in the early 2000s and based on the better understanding of the biology of cancer, new drugs have been developed that target specific molecular pathway in malignant cells. There has been a significant shift from the development of classic cytotoxic agents toward targeted therapies. Dose limiting toxicities of target therapies are often different. These agents have unique mechanism of action and are very specific for one or several key cellular biologic pathways. Introduction of these agents was associated with a significant progress in the management of some cancers. A good example is use of tyrosine kinase inhibitor (TKIs) for the treatment of chronic myeloid leukemia. Imatinib was the first one and several other TKIs such as dasatinib, nilotinib, bosutinib and ponatinib have been developed.

Background and purpose: Proton pump inhibitors (PPIs) are one of the main therapeutic agents for acid-dependent diseases. Inappropriate use of this group of drugs especially Intravenous form of pantoprazole can lead to unnecessary cost. The aim of this study was to assess the IV Pantoprazole utilization in a teaching hospital in North of Iran. Materials and methods: This cross sectional study was performed within four months in 100 patients hospitalized in Ramsar Imam Sajjad Hospital, 2016. Demographic data, type and doses of Pantoprazole, risk factors for stress ulcer, and other relevant clinical data were recorded. Appropriate use of Pantoprazole was assessed according to recommendations provided by Fact Drug Information 2016, Medscape 2016, and UpToDate 2016. Results: Among the patients 54% had indication for receiving a PPI and only 16% had indication for parenteral form of PPI. Oral PPIs could have been used in 73% of the patients but they received parenteral form of Pantoprazole. In 92% of IV injections, a vial of 40 mg Pantoprazole was dissolved in 10 ml distilled water and injection was done in less than 10 seconds which was incompatible with guidelines. Conclusion: In current study, utilization of Pantoprazole was not compatible with guidelines in most cases, including right indication, right preparation methods and right rate of drug administration.

Background: Caffeine is widely used for prevention of apnea and helps successful extubation from mechanical ventilation. It facilitates the transition from invasive to noninvasive support and reduces duration of continuous positive airway pressure (CPAP) in preterm infants. The optimum caffeine dose in preterm infants has not been well-studied in terms of benefits and risks. We compared efficacy and safety of once versus twice-daily caffeine dose in premature infants. Methods: This study was a randomized clinical trial conducted in Bu-Ali Sina Teaching Hospital, Sari. Patients with gestational age of

Background: Methotrexate (MTX) is commonly used in the hematology-oncology units and is frequently associated with adverse effects. High-dose methotrexate (HDMTX) is indicated in the treatment of acute lymphoblastic leukemia (ALL), osteosarcoma, systemic non-Hodgkin lymphoma and primary central nervous system (CNS) lymphoma. The side effect profile of MTX varies markedly according to dose. The aim of this study was to evaluate the uses and adverse effects of HDMTX in a cancer center in north of Iran. Methods: This cross-sectional descriptive study carried out in Emam Sajjad Hospital, Ramsar, Iran from June 2016 to July 2017. Doses more than 500 mg/m2 of MTX was considered as a high-dose. Hydration status, evaluation of the renal and hepatic function, blood tests, urine pH, doses and frequencies of leucovorin administration, measurement of serum levels of MTX and side effects were evaluated. Recommendations of UpToDate 2017 were considered as standards of administration of HDMTX. Results: Forty-four courses of HDMTX were evaluated in this study. HDMTX were prescribed for lymphoma (30 cases), ALL (8 cases) and osteosarcoma (6 cases). In all patients, hydration was done with 1340.9±894 normal saline plus 25 ml sodium bicarbonate 8.4%, one to two hours before HDMTX. The solution used for dilution of MTX was 5% dextrose (1022.7±105.5 ml). Urine pH was not measured in any patient. The frequency of leucovorin administration was 5.64±3.03 times with doses of 17.6±1.7 mg/m2 every 6 hours. Serum levels of MTX were not measured in any patient. Blood urea nitrogen and creatinine measurement was carried out before administration of HDMTX in all patients. The most common adverse effects were nausea (64.4%), anxiety (44%) and headache (43.2%). Conclusion: The appropriate aspects of HDMTX usage were good hydration, urine alkalinization with bicarbonate and administration of leucovorin in patients receiving HDMTX, whereas monitoring of serum levels of MTX and administration of bicarbonate based on urinary pH were not done in any of the patients.

Background and purpose: Considering the importance of pain management in cancer patients, this study aimed to assess the prevalence of pain, its severity, analgesics used to control pain, and the extent of pain control in cancer patients attending a medical center in North of Iran. Materials and methods: One hundred cancer patients attending Ramsar Imam Sajjad Hospital (2015) were prospectively enrolled in the study. Clinical and demographic data and all analgesics used were recorded. Pain intensity were determined based on the Numeric Rating Scale from 0 (pain-free) to 10 (the most severe pain ever experienced) in two sequential visits, 3 weeks apart. Results: The average age of participants was 54.7±3 years. NSAIDs (98 cases, 98%) and opioids (49 cases, 49%) were the most common analgesics prescribed. Among opioids, codeine (67.3%) and morphine (24.5%) were used more frequently. The pain score was 3.94±0.342 at first visit and 3.65±.316 following analgesic use (P=0.002). For opioid users, the pain scores were 4.29±0.53 and 3.84±0.506, respectively (P=0.007). Conclusion: The pain scores statistically reduced, however, the decrease was not clinically prominent since the pain severity was between 3 and 4 in NRS scale. More attention to pain control is recommended in cancer patients while considering the standard pain management guidelines.

Purpose: Propranolol is the most widely used treatment for cardiovascular diseases. Dosage range in our patients is usually less than the amount mentioned in references. The aim of the present study was to clarify whether pharmacokinetic differences are able to justify the need for the fewer doses in our patients or not. Methods: Twenty healthy volunteers (10 male) at heart center of Mazandaran University of Medical Sciences were studied. Samples of blood were collected before a single oral dose (40 mg) of Propranolol. Blood samples were taken up to 9 hours after dose. Total plasma concentration of Propranolol was measured by HPLC. Population Pharmacokinetic analysis was performed using population pharmacokinetics modeling software P-Pharm. Results: The mean value for oral plasma clearance (CL/F) was 126.59 ml/hr. The corresponding values for apparent volume of distribution (V/F), t1/2 beta, maximum blood concentration (C max), and time to reach the maximum blood concentration (T max) were 334.12 Lit, 1.98 hr, 40.25 ng/ml, and 1.68 hr, respectively. The observed mean values of V/F of propranolol in the present study were comparable with those reported in the literature. However, the mean values of CL/F of propranolol in current study was significantly higher than those reported in other population (P-value

Background: Chemotherapy-induced nausea and vomiting (CINV) is considered as the most common complications of chemotherapy which has a detrimental influence on the quality of life of patients with cancer. We assessed the efficacy of Apple (Malus domestica) syrup for reducing CINV. Materials and Methods: This study was a randomized, double-blind, placebo-controlled trial carried out in a Hematooncology Clinic affiliated to Mazandaran University of Medical Sciences, Sari, Iran (from October 2017 to August 2018). Subjects were randomly allocated to receive apple syrup or placebo along with their previous antiemetic treatment and chemotherapy regimen, three times a day. Thirty-four patients received apple syrup (n = 16) or placebo (n = 18). Statistical analysis was conducted using SPSS software Version 21® (SPSS Inc., Chicago, IL, USA). A P < 0.05 indicated statistical significance. Results: Both acute and delayed nausea grades were significantly lower in M. domestica syrup in comparison to placebo syrup (P = 0.001 and 0.001, respectively). The duration of nausea (P = 0.04) was lower in intervention group compared to placebo group. Conclusion: These findings demonstrated that M. domestica syrup can reduce the severity and duration of nausea in cancer patients who received chemotherapy.

Surgical site infections are one of the most important post-surgery complications. Antimicrobial prophylaxis has been used routinely in surgeries to reduce infection incidence. However, inappropriate selection of antimicrobial agents or dosing can develop antimicrobial resistance, serious adverse reactions and prolong hospitalization. Current study aimed to examine prophylactic antibiotic prescription in surgeries in a teaching hospital in Sari, Mazandaran and evaluate level of adherence to the international guidelines. Between January 2015 to May 2015, 104 patients in general surgery ward were selected and enrolled in the study. The prophylactic antibiotics, dosage, timing and duration of administration were collected by reviewing patients’ records and compared to the existing guidelines. Prophylactic antibiotic was given to 85.5% of patients. Prescribed antibiotics were cefazolin (46.1%), metronidazole (24%), ceftriaxone (12.5%), ciprofloxacin (1.9%) and vancomycin (0.96%). Most of the patients (62.9%) received an inappropriate and delayed timing. Proper antibiotic dosage was seen in 45.2% of patients. All patients received post-operative prophylactic antibiotic. Main antibiotics include cefazolin (41.3%), metronidazole (33.7%), ceftriaxone (31.7%) and clindamycin (20.2%). Only 10 (21.9%) patients received cefazolin or vancomycin for a total duration of 48 hours or less. Surgical wound infection occurred in 17 (16.3%) patients during hospital stay. Adherence to antimicrobial prophylaxis guidelines was completely achieved in 14.4% of cases. Results of this study signified that adherence to existing guidelines was poor and the most common mistakes were over usage, inappropriate dosage and choosing of antibiotics.

Background: Resistance to antimicrobial agents including aminoglycosides (AGs) is a great concern that is mainly related to inappropriate use. Since there were not adequate data regarding how rationally AGs are being prescribed in our critically ill patients, this study was conducted to determine the main issues in the area of appropriate use of this antibiotic class. Methods: One hundred patients who were in the intensive care units (ICUs) of Imam Khomeini Teaching Hospital from February 2012 to August 2012 were included. A data gathering form was prepared based upon the recommendations provided by Up-to-date (20.1) 2012 and Medscape 2013. All demographic characteristics and other information about time of beginning and duration of dosage, interval of administration of AGs and creatinine (Cr) level were collected. In statistical analysis, SPSS Version 16 software was used. Independent samples t-test was used to compare the quantitative and chi-square for qualitative variables. Results: Sixty six (66%) of patients received gentamicin and 38% received amikacin. In 27% of patients, serum creatinine (Cr) had been checked before and after AGs administration and 4 patients had no renal function monitoring. Monitoring of serum concentration and Cr clearance estimation was not carried out for any patients. Culture and laboratory sensitivity tests were done on 17 patients and E-coli (57%) was the most common isolated organism. Conclusion: The results of this study revealed that majority of the hospitalized patients in the ICU and the dosage of AGs had not been adjusted to renal function.

Aminoglycosides (AGs) are frequently used in pediatric settings, especially for empiric treatment of early-onset neonatal sepsis. Although AGs are used for several decades, the optimum method of administration and their dosing schemes needs more clarification. The risks of ototoxicity and nephrotoxicity, two main toxicities associated with AGs, have been contributed to the peak and trough plasma levels, respectively. One approach to decrease these potential toxicities of AGs is to administer higher doses with a prolonged interval, named extended-interval dosing (EID). Post-antibiotic effect (PAE) and concentration-dependent killing of AGs provide rational basis for the efficacy of EID. PAE refers to the extended bactericidal activity of AGs against many Gram-negative organisms after the drug was removed by metabolism. One concern is that the higher initial peak concentration with EID may be accompanied with more toxicities, especially ototoxicity. It was demonstrated that due to saturation of binding site of AGs in renal and cochlear tissues, transiently higher concentration of AGs does not cause additional nephrotoxicity or ototoxicity. Experience and clinical evidence regarding EID in pediatrics is suboptimal. In this review, we presented the rational and studies focusing on EID in pediatric setting. The overall finding of trials is that in pediatric setting, EID is a safe and effective dosing method. The risk of serum drug concentration outside the therapeutic range is lower in neonates treated with EID, leading to less need of therapeutic drug monitoring (TDM) with EID. Moreover, there are evidences supporting lower chance of bacterial resistance with EID compared with traditional dosing approach.

Gastric cancer has been known as a poor prognosis disease with a high degree of mortality. In Iran, it has been increased during the previous two decades, especially in northern part of the country. The aim of this study was to determine the demographic and clinical characteristics of gastric cancer in Mazandaran province. All patients with gastric cancer diagnosis treated in the Imam Khomeini educational hospital or Touba Polyclinic, a university affiliated center, from March 2008 to March 2014 were included. Demographic data, the symptoms at the time of presentation, tumor size, type of tumor, lymph node involvement, status in terms of metastatic disease, therapeutic plan and type of chemotherapy regimens were gathered from patients’ medical records. Statistical analysis was performed using SPSS, version 16. Totally, 643 patients were investigated. The mean age of patients was 64.34 years and men were more affected than women. “Time to relapse” and “time to progression” were 13 and 6.5 months, respectively. The most common initial symptoms at diagnosis were nausea, vomiting and epigastric pain (47.4%). Only in 6.3%, the disease was diagnosed at the initial stages. The most common site of involvement was cardia (almost 40%) and antrum (32%). More than 91% of tumors were adenocarcinoma. DCF (Docetaxel, Cisplatin, 5FU) (43.3%), Xeloda (15.2%), DOX (Docetaxel, Oxaliplatin) (13.8%) and ECF (Epirubicin, Cisplatin.5FU) (9.2%) were the most common used regimens. There was a trend for improved survival with DCF regimen (P = 0.08). Most gastric cancer patients were referred in the advanced stage or metastatic disease. The demographic characteristics are consistent with other previous reports. DCF regimen may have some advantages over other chemotherapy regimens.

Objective: The inappropriate use of antibiotics remains the primary factor in antimicrobial drug resistance. In this study, we evaluate the use of meropenem in surgical/medical wards of Imam Khomeini Tertiary Referral Hospital, Sari, Iran. Methods: This retrospective observational study was used to assess rational use of meropenem. The study was conducted by reviewing medical records of 100 admitted patients who received meropenem during March 2013 to January 2014. Findings: Meropenem was prescribed most frequently in Intensive Care Unit (22%), and pneumonia was the most common diagnosis (35%). The third-generation cephalosporins were the most frequently prescribed antimicrobials after meropenem (53%). In 21% of the patients, imipenem was changed to meropenem. Most of the inappropriate uses were seen in terms of frequency of meropenem use (34%), followed by duration of meropenem therapy (28%). Conclusion: Comparing our study results has shown higher inappropriate use. It is necessary to take action to improve prescribing habit in order to reduce the unnecessary usage of antibiotic thus enhance rational antibiotic use.

Introduction: Gastrointestinal tract cancers are the most common cancers in Iran with a growing incidence in the past two decades, especially in the Northern provinces of the country. Different chemotherapy regimens have been used in the treatment of colorectal cancers (CRC). Considering lack of data, this study aimed to determine the adverse drug reactions (ADRs) of chemotherapy regimens used in treatment of patients with CRC. Material and methods:This cross-sectional prospective study was carried out in Emam Khomeini Hospital and Tooba Clinic, both affiliated to Mazandaran University of Medical Sciences. ADRsof chemotherapy regimens including nausea, vomiting, fever and neutropenia, diarrhea, oral mucositis, neuropathy and hair loss were documented based on CTCAE Version 4.0 (Common Terminology Criteria for Adverse Events). Results:Two hundred sixty seven different courses of chemotherapy regimens received by 48 patients were evaluated in terms of adverse events. Three more common chemotherapy regimens wereFOLFOX (Folinic acid, Fluorouracil, Oxaliplatin), FOLFIRI (Folinic acid, Fluorouracil, Irinotecan) and XELOX (Capecitabine, Oxaliplatin).FOLFIRI and FOLFOX regimens were associated with more nausea and vomiting compared to XELOX. The rate of vomiting was marginally different between regimens (P=0.06). Most of nausea and all vomiting were as grade 1 or 2. The diarrhea was more common with FOLFOX (P=0.027). Whereas 14% of patients received FOLFIRI experienced neutropenia, none of patients in XELOX and almost 5% of FOLFOX patients experienced neutropenia. Mucositis happened in 16.1 and 17.8% of patients received FOLFOX and XELOX, respectively. The rate of neuropathy was different among regimens, as XELOX and FOLFOX were associated with more neuropathy compared with FOLFIRI (P=0.019). The rate of hair loss and headache were not different between three regimens.Most of the side effects (e.g., nausea, neuropathy, and headache) were acute. Vomiting and mucositis with XELOX occurred after 24 hours of initiation of chemotherapy. Conclusion:The results of our study showed that the GI adverse events including nausea, vomiting and severe diarrhea were more common with FOLFIRI regimen. Mucositis and neuropathy were more common with XELOX. Hair loss was more common with FOLFIRI followed by XELOX and FOLFOX.

Background: Venous thromboembolism (VTE) is a major cause of mortality among cancer patients. The aim of this study was to evaluate drug regimens used for the prophylaxis of thromboembolic events in cancer patients. Methods: A retrospective study was conducted using medical records of patients hospitalized from March 2012 to March 2014 at Cancer Division of A tertiary university-affiliated hospital in North of Iran. The risk factors of patients regarding need of venous thromboembolic (VTE) prophylaxis were recognized and dosage and duration of thromboembolic prophylactic agents were evaluated according to the National Comprehensive Cancer Network (NCCN) 2012 guidelines. Statistical analysis was performed using SPSS v.23. Results: Of a total of 1160 medical records, VTE prophylaxis regimens of 186 patients were evaluated. In 18(13.1%) and 15(10.9%) of patients, administrations were compatible with NCCN guidelines with respect to the "type of drug" and "dosage", respectively. Only in 7(5.1%) of patients administrations were compatible with respect to the "duration of thromboembolic prophylaxis regimen". Forty patients (21.7%) had relative contraindication for thromboembolic prophylaxis and 7(3.8%) patients had absolute contraindication. In 32(80%) of 40 patients with relative contraindications and only in 1(14.3%) of 7 patients with absolute contraindications, physicians’ orders were compatible with NCCN guidelines. Conclusion: The rate of concordance of the VTE prophylaxis with recommendations provided by NCCN is very poor. This study emphasizes need of a multidisciplinary action to improve the VTE prophylaxis in cancer patients.

Major β-thalassemia (β-TM) is one of the most common inherited hemolytic types of anemia which is caused as a result of absent or reduced synthesis of β-globin chains of hemoglobin. This defect results in red blood cells lysis and chronic anemia that can be treated by multiple blood transfusions and iron chelation therapy. Without iron chelation therapy, iron overload will cause lots of complications in patients. Antioxidant components play an important role in the treatment of the disease. Silymarin is an antioxidant flavonoid isolated from Silybum marianum plant. In the present study, we reviewed clinical and experimental studies investigating the use of silymarin prior to September 1, 2015, using PubMed, ISI Web of Knowledge, Science Direct, Scopus, Ovid, and Cochrane Library databases and we evaluated the potential effects of silymarin on controlling the complications induced by iron overload in patients with β-TM. Based on the results of the present study, we can conclude that silymarin may be useful as an adjuvant for improving multiple organ dysfunctions.

Background: Selenium (Se) is an essential trace element mainly obtained from seafood, meat, and cereals. Se deficiency has been identified as a major contributing factor in the pathogenesis of certain congestive heart failure (CHF) syndromes. Since there is controversy over the prevalence of Se deficiency among patient with CHF, the aim of this study was to assess the serum Se concentrations in patients with CHF and compared them with the Se status of healthy controls.Methods: The study included 77 patients (age, 68.4 ± 10.4 years old; 40.3% female) and 73 healthy volunteers (64.9 ± 4.7 years old; 35.6% female). A complete medical/drug history and physical examination were performed for all patients and healthy volunteers. All patients had symptoms and signs of CHF and had a left ventricular ejection fraction (EF) of < 40% obtained by echocardiography. The Se concentration was assessed by atomic absorption spectrometer with the Graphite Tube Atomizer. The limit of measurement was 5 μg/L. Results: The Se concentrations in CHF patients did not show a significant difference from those of healthy controls (185.9 ± 781.2 μg/L vs. 123.3 ± 115.5 μg/L, respectively; p value = 0.499). There was no correlation between serum Se concentrations and EF in both the normal group and the patients with heart failure (p value = 0.96 and 0.99; r = 0.006 and 0.002 for patients and healthy volunteers, respectively).Conclusion: In this study, serum Se levels in CHF patients were similar to those of controls and the Se concentrations did not correlate with the degree of left ventricular dysfunction.

Background: The primary side effect of adjuvant chemotherapy with taxanes is the taxane-induced peripheral neuropathy (TIPN), which may have substantial negative impacts on patients' quality of life (QOL). We investigated the effect of pregabalin and duloxetine on QOL of breast cancer patients who experienced TIPN. Materials and Methods: This was a randomized, double-blind clinical trial conducted at a chemotherapy center of Mazandaran University of Medical Sciences, Sari, Iran. Breast cancer patients 18 or more years old were included if they received paclitaxel or docetaxel and experienced neuropathy grade one or higher; and neuropathic pain score of four or more. Patients were treated with pregabalin or duloxetine until 6 weeks. Assessment of sensory neuropathy and QOL was performed at baseline, and 6 weeks after the initiation of the treatment. Results: At baseline, the mean score of global health status/QOL scale for pregabalin and duloxetine groups were 61 (standard deviation [SD]; 5.11) and 60.28 (SD; 5.44), respectively (P = 0.54). After 6 weeks, both interventions were associated with improvement of global QOL compared to baseline. The global health status/QOL score was not different between two groups after 6 weeks. While the emotional functioning was improved more favorably with duloxetine (P < 0.001); pregabalin was associated with more improvement in insomnia and pain scores (P = 0.05 and P < 0.001, respectively). Conclusion: Pregabalin as well as duloxetine improve the global QOL of breast cancer patients with TIPN. Different effects of treatments on subscale of QLQ-C30 could help clinicians to select the appropriate agent individually.

Background: Serum trace element alteration has been reported in dilated and ischemic cardiomyopathy. The reports were controversial. We have studied serum Zinc level in cardiomyopathy patients in northern province of Mazandaran and compared them with healthy volunteers. Methods: Serum Zinc level was measured in 30 ischemic and 18 dilated cardiomyopathy patients against 27 healthy volunteers. It was measured using atomic absorption spectrophotometry. Statistical analysis was performed using SPSS for Windows version 14 and independent t-test was used for comparing serum Zinc level in ischemic and dilated cardiomyopathy. Pearson correlation and ANOVA tests were used for numeric variables in three different groups. P

Background: DUE (Drug Utilization Evaluation) studies can help identify and correct problems associated with irrational use of drugs. Considering lack of data regarding how rational vancomycin is being used, we evaluated this DUE study in a referral infectious center to evaluate compliance with guidelines in terms of rational use of this valuable antibiotic. Methods: This retrospective study was done for 6 months from March to September 2012 at Razi hospital, an educational hospital affiliated to Mazandaran University of Medical Sciences. Data including patients’ demographics, vancomycin dose, kidney function assessment, dose adjustments, sampling and culture were collected. Based on the HICPAC (Hospital Infection Control Practices Advisory Committee) and Up-to-date 2012 advices, the concordance of practice with standard guidelines was assessed. Results: One hundred and forty six medical records were reviewed in this study. Fever and shortness of breath were the most common symptoms at the time of initiation of vancomycin. Skin infections, lower respiratory tract infection and septicemia were the most common initial diagnosis of patients. Sampling was done in almost one-third of patients. Most of patient with a specific order were received vancomycin in half an hour. Considering the indication, Vancomycin was administered appropriately in 58 percent of patients. Conclusion: Vancomycin was used irrationally in a great proportion of patients. The main observed drawbacks were empiric use of vancomycin without subsequent adjustment of antimicrobial agent according to culture and sensitivity data and lack of paying enough attention to calculation of creatinine clearance and dosage adjustment.

Abstract: Warfarin is the most commonly used oral anticoagulant drug in clinical practice with extreme inter and intra-individual variation in pharmacokinetic properties. Na Valproate, a broad spectrum anticonvulsant agent, is best known for its enzyme inhibition properties and also displacement of protein binding sites. Interaction between Warfarin and psychotropic drugs including Valproate are important and perhaps under recognized. In this report, we present a 48 year old female patient with chief complaints of abdominal pain, tea-color urine, blurred vision and headache. She had been suffering from “migraine headache” for 15 years that was relatively well controlled with Na Valproate 200mg twice daily. She was experienced a deep vein thrombosis (DVT) following oral contraceptive. For management of DVT, she was received Warfarin 5mg/day which was increased to 7.5 mg /day after 2 weeks. Three days after this increment of dose, her Prothrombin Time (PT) rose to 35.3 seconds (three times of normal value) and evidences of bleeding including hematuria and hematemesis were observed. Based on the history and laboratory findings, “Warfarin toxicity” was the first impression and she was treated with fresh frozen plasma and vitamin K with a well recovery. This experience emphasizes the clinical significant interaction between Warfarin and Na Valproate, which may take place even with the usual doses of each agent.

Background: Following establishment of Iranian Adverse Drug Reaction (ADR) Monitoring Center in 1997, ADR committees were established in all hospitals of Mazandaran Province of Iran. Clinical pharmacists from Mazandaran University of Medical Sciences have been involved with these committees since 2007. The aim of this study was to compare the results of the pharmacovigilance system before and after active involvement of clinical pharmacists. Methods: This study included Yellow Cards filled out by healthcare providers inMazandaran Province during 2004-2010. Frequency of Adverse Drug Reactions (ADRs), route of administration, reporters, number of reports in each years and damaged organs were focuses. Statistical analysis was performed by SPSS 16 software. P< 0.05 was considered as significant difference. Results: A total of 793 yellow cards were completed during 2004 – 2010. Only 38 ADRs(4.8%) were related to 2004-2007. Most of the reports generated by Nurses (49.3%) followed by Pharmacists and Physicians (P< 0.001). Forty-one reactions (5.2%) were serious, most related to Ceftriaxone, Desfonac and Vancomycin. Conclusion: Clinical pharmacists’ intervention regarding establishing ADR committees in the hospitals improved the output of the pharmacovigilance system, although under- reporting is still a major drawback of spontaneous reporting.

Backgrounds: All of Long-acting β2-agonists are beneficial in maintenance treatment of asthma but their use in relieving acute asthma attacks is not well known. The aim of this study was to compare rapid bronchodilatory effects of Salmeterol and Formoterol in patient with moderate to severe asthma. Methods: It was a randomized, double blind, cross-over study on 60 patients with moderate to severe asthma. Patients randomly received 50 micrograms of salmeterol or 18 micrograms of formoterol and after one-week washed out period exchanged their medications. All patients undergone spirometry for four times (before receiving the drugs, as well as 3, 30 and 60 minutes after drug inhalation) and Forced Expiratory Volume in 1 second (FEV1), Forced Vital Capacity (FVC), FVC percentage predicted value, FEV1/FVC, Peak Expiratory Flow Rate (PEFR) and PEFR percentage predicted value were measured. Results: Both medications could significantly increase FEV1/FVC and PEFR at 3, 30 and 60 minutes after inhalation (P

Asthma is the most common chronic inflammatory disorder characterized by cough, wheezing and dyspnea in children. Nutrition is an important factor which influences on induction and exacerbation of asthma. There are controversies to use Vitamin E in asthmatic patients. The aim of this study was to evaluate the effect of vitamin E supplement in children with moderate asthma. This is a randomized double blind placebo-controlled trial performed on children (age 2-17 years old) with moderate asthma (5-17 years old) from March 2010 to March 2012. Case group were treated with fluticasone and vitamin E (50mg/day) and control group received fluticasone plus placebo for 8 weeks. Out of 300 cases, 240 cases completed the study. Female to male ratio was 0.84. Serum level of Vitamin E significantly increased after treatment in intervention group. FEV1 and FEV1/FVC ratio was ignificantly improved in case group compared to the control group. It can be concluded that vitamin E supplement could improve clinical manifestations and pulmonary function test in children with moderate asthma.

Conventional dissection surgery (CDS) or using the Plastibell device (PD) is the method most frequently employed for circumcision. The aim of this study was to evaluate two methods in terms of the incidence of complications in infants of ages up to 12 months. In a prospective study, 586 infants equal to or less than 12 months were studied from 2002 to 2008, and complications between the two groups were assessed. The overall rates of complications in CDS and PD groups were 1.95% and 7.08%, respectively. In each group, the rate of complications was not different among children who had a normal weight, compared to those of a lower or upper (10%) weight. There was a significant positive correlation between the age and weight of subjects within the time of ring separation (𝑃