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More than half of cancer patients need radiotherapy during the course of their treatment. Despite the beneficial aspects, the destructive effects of radiation beams on normal tissues lead to oxidative stress, inflammation, and cell injury. Kidneys are affected during radiotherapy of abdominal malignancies. Radiation nephropathy eventually leads to the release of factors triggering systemic inflammation. Currently, there is no proven prophylactic or therapeutic intervention for the management of radiation-induced nephropathy. This article reviews the biomarkers involved in the pathophysiology of radiation-induced nephropathy and its underlying molecular mechanisms. The efficacy of compounds with potential radioprotective properties on amelioration of inflammation and oxidative stress is also discussed. By outlining the approaches for preventing and treating this critical side effect, we evaluate the potential treatment of radiation-induced nephropathy. Available preclinical and clinical studies on these compounds are also scrutinized.

This study aimed to assess the antioxidant effects of amlodipine in transfusion-dependent β-thalassemia (TDT) patients.This crossover trial consisted of two sequences (AP and PA). In the AP sequence, nine cases received amlodipine 5 mg daily (phase I) and then were switched to placebo (phase II). In PA sequence, 10 patients took the placebo (phase I) and were shifted to amlodipine (phase II). The washout period was 2 weeks. The length of each phase was 6 months. Serum malondialdehyde (MDA, μmol/L), carbonyl (protein CO, μM/L), glutathione (GSH, nM/L), and total antioxidant capacity (TAC, μmol FeSO4/L) were measured in the beginning and at the end of phases I and II. The clinical significance was viewed as a minimum change difference of 5% for each outcome between amlodipine and placebo.Seventeen cases completed the study. According to the baseline MDA values, the adjusted Hedges's g for MDA was -0.59, 95% confidence interval [CI] -1.26 to 0.08. After controlling the baseline protein CO values, Hedges's g computed for protein CO was -0.11, 95% CI -0.76 to 0.55. The estimated values of the adjusted Hedges's g for GSH and TAC were also 0.26, 95% CI -0.40 to 0.91, and 0.42, 95% CI -0.24 to 1.09, respectively. The change difference for MDA was 8.3% (protein CO 2.2%, GSH 3.1%, and TAC 12.9%).Clinically, amlodipine therapy is an efficacious adjuvant treatment with conventional iron chelators for improving the levels of MDA and TAC in patients with TDT.

Background: Meropenem standard doses are based on the minimum inhibitory concentration of sensitive pathogens and the pharmacokinetic parameter of not critically ill patients. We compared the efficacy of high versus standard dose of meropenem in ventilator-associated pneumonia (VAP). Methods: 24 out of 34 eligible patients were randomized to receive meropenem 3 g q8h (high dose group, 11 patients) or 2 g q8h (standard-dose group, 13 patients) as a 3h infusion. The primary outcome was considered as clinical success that was defined as stable hemodynamic, improved sequential organ failure assessment (SOFA) score, stable or improved PaO2/FiO2 after 7 days. Sputum culture was taken before the intervention. Results: Clinical success rate was not significantly different between the high and standard-dose group (54.5% vs. 38.5%, P= 0.431). There was a significant difference in the reduction of clinical pulmonary infection score (CPIS) compared to a high dose to the standard group (P=0.038). SOFA score declined significantly in the high dose group throughout the study (P=0.006). A shorter duration of VAP treatment was recorded in the high dose group (P=0.061). We did not observe any significant adverse event related to meropenem. Acinetobacter spp. (34.8%), Klebsiella spp. (32.6%) and Pseudomonas aeruginosa (19.5%) isolated more frequently from sputum cultures. Conclusion: Treatment with the high dose of meropenem seems to be safe. However, it did not provide a significantly higher clinical success rate in comparison with the standard dose, but could be considered as an appropriate empirical treatment in patients with severe infection due to reduction in SOFA and CPIS. The trial protocol was registered with IRCT.ir (registration number IRCT2010010700 3014N19 in April 2018).

To examine the preventive effects of Aloe vera in colorectal cancer patients undergoing radiotherapy. Twenty colorectal cancer patients, who received radiation, were randomized to receive Aloe vera 3% or placebo ointment, 1 g twice daily for 6 weeks. At weekly visits, acute radiation proctitis (ARP) was evaluated by Radiation Therapy Oncology Group and clinical presentation criteria as the primary endpoint. We also evaluated secondary endpoints of quality of life, psychosocial status, by applying Hospital Anxiety-Depression (HAD) Scale and laboratory measures of quantitative measurement of C-reactive protein (CRP) as a marker for systemic inflammation. There was a significant improvement in the symptom index (before treatment vs. after treatment with Aloe vera) for diarrhea (p = 0.029, median score: 0.5 vs. 0.001). The overall primary and secondary outcomes favored Aloe group, while the measures of toxicity did not achieve a statistical significant difference. The lifestyle score improved significantly with A. vera (p = 004), and they also had a lower depression score in HAD scale (p = 0.008). Furthermore, quantitative CRP decreased significantly during the course of treatment with Aloe vera. The use of topical formulation of Aloe vera 3% diminishes the severity of ARP in colorectal cancer patients.

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.

In β-thalassemia major (β-TM) patients, iron overload is one of the main causes of inflammation. This study investigated whether use of silymarin could improve inflammatory status in patients with β-TM and iron overload, through a placebo-controlled, crossover study.Silymarin (140 mg, 3 times a day) or placebo were prescribed to all patients (n = 82) for 12 weeks, and after a 2-week washout period, patients were crossed over to the other group. The efficacy of silymarin was assessed by measuring serum C-reactive protein (CRP) (mg/dL), interleukin (IL)-6 (pg/mL), and IL-10 (pg/mL).Sixty-nine patients completed the study. Data analysis showed that compared to the placebo, silymarin could decrease CRP, IL-6, and raise IL-10 significantly (the p values for all variables were0.001). Cohen's d for CRP adjusted according to the baseline CRP value was -1.72, the 95% confidence interval (CI) -2.12 to -1.33. The adjusted Cohen's d equal to -1.12, 95% CI -1.48 to -0.76, and 0.78, 95% CI 0.43-1.12, were also estimated for IL-6 and IL-10, respectively.The results of the current study demonstrate that the combination of iron chelation therapy with silymarin can improve inflammatory status in patients with β-TM in the clinical setting.Hintergrund: Bei Patienten mit β-Thalassaemia major (β-TM) ist Eisenüberladung eine der Hauptursachen für Entzündungsprozesse. Hier wurde in einer plazebokontrollierten Crossover-Studie untersucht, ob sich durch Anwendung von Silymarin der Inflammationsstatus von Patienten mit β-TM und Eisenüberladung verbessern lässt. Methoden: Allen Patienten (n = 82) wurde entweder Silymarin (140 mg, dreimal täglich) oder Plazebo für 12 Wochen verordnet, gefolgt von einer 2-wöchigen Auswaschphase und dem Wechsel zur jeweils anderen Gruppe. Die Wirksamkeit von Silymarin wurde an der Konzentration von C-reaktivem Protein (CRP) (mg/dl), Interleukin (IL)-6 (pg/mL) und IL-10 (pg/mL) gemessen. Ergebnisse: 69 Patienten schlossen die Studie ab. Die Datenauswertung ergab, dass Silymarin im Vergleich zu Plazebo eine signifikante Reduktion der CRP- und IL-6-Konzentration und Erhöhung der IL-1-Konzentration zu bewirken vermochte (die p-Werte für alle Variablen waren0,001). Cohens d für CRP, angepasst nach dem CRP-Wert zu Studienbeginn, betrug –1,72 (95%-Konfidenzintervall [KI]: –2,12 bis –1,33). Auch für IL-6 und IL-10 wurden Schätzungen für Cohens d ermittelt; sie betrugen –1,12 (95%-KI: –1,48 bis –0,76) bzw. 0,78 (95%-KI: 0,43–1,12). Schlussfolgerung: Die Ergebnisse dieser Studie belegen, dass die Kombination aus Eisenchelator-Therapie und Silymarin den Entzündungsstatus von Patienten mit β-TM im klinischen Setting verbessern kann.

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.

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 P = 0.048). Incidence of the DPD IVS14 + 1 G > 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.

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.

Background and aims Gabapentin has been used for the management of radiotherapy and chemotherapy induced stomatitis in a number of studies. Due to lack of sufficient evidence, the present study was designed to evaluate the efficacy of gabapentin mouthwash in oral mucositis associated pain in patients undergoing cancer chemotherapy. Methods and results This study was a prospective, randomised, double-blind, placebo-controlled trial. The patients were randomly divided into two groups receiving either the gabapentin or placebo mouthwash. Patients were advised to rinse their mouth with 7 ml of solution for 30 s three times a day and were visited 10 days after initiation of the trial. The intensity of pain and severity of oral mucositis were assessed. Thirty-one patients received gabapentin mouthwash while 27 patients received placebo. Both gabapentin and placebo mouthwashes had decreased the pain intensity almost equally and did not show a significant difference between the two groups (P = 0.73). Also both gabapentin and placebo had reduced and improved swallowing, inflammation and erythema. But there was no noticeable difference between groups (P > 0.05). Conclusions These findings indicate that gabapentin mouthwash did not show a significant activity as a pain relieving agent in chemotherapy induced oral mucositis associated pain.

Septic shock, known as the most severe complication of sepsis, is a serious medical condition that can lead to death. Clinical symptoms of sepsis include changes in body temperature in the form of hypothermia or hyperthermia, tachypnea or hyperventilation, tachycardia, leukocytosis or leukopenia, and variations in blood pressure, as well as altered state of consciousness. One of the main problems in septic shock is poor response along with reduced vascular reactivity to vasopressors used to increase blood pressure. Therefore, low vascular response associated with reduced sensitivity or lower number of alpha-1 agonist receptors can result in shock and death. In addition to being the state-of-the-art treatment including volume load and vasopressor, use of alpha-2 agonists e.g. dexmedetomidine (DXM) in septic shock can reduce vasopressors needed to restore adequate blood pressure. They can further moderate massive release of endogenous catecholamine. Therefore, the purpose of this study was to investigate the effect of DXM on outcomes of patients with septic shock, especially their needs for vasopressors and impacts on their hemodynamic status. This single-blind randomized controlled trial was performed on a total number of 66 patients with septic shock admitted to the intensive care unit (ICU) of Imam Khomeini Teaching Hospital in the city of Sari, in northern Iran. To this end, DXM (0.6 µg/kg/h) and normal saline (6 mL/kg/h) were infused for 12 h in the study and control groups, respectively. The results revealed that DXM could increase mean arterial pressure (MAP) (P = 0.021), systolic blood pressure (SBP) (P = 0.002), and reduced heart rate (P < 0.001) but diastolic blood pressure (DBP) (P =0.32) and norepinephrine dose requirement didn’t change statistically in septic shock patients (P = 0.12).

As a common intervention among burn patients, skin graft has some risks such as infections and delay of wound healing. The aim of this study was to assess the efficacy and safety of topical 0.25% Timolol Gel (TG) in promoting wound healing in split-thickness skin graft donor sites. We conducted a double-blind, randomized clinical trial to assess re-epithelialization time, the level of pain based on the Visual Analog Scale (VAS), and the wound infection incidence. The scar status was also evaluated by the Vancouver Scar Scale (VSS) and the Patient and Observer Scar Assessment Scale (POSAS). Totally, 64 patients were randomly assigned to the study groups. The two groups showed a significant difference in healing time (14.5 ± 3.2 vs. 11.5 ± 2.3 days, P < 0.001). No infection occurred in either group, and 3 cases of transplant rejection were observed in the placebo group. The VAS was significantly different on days 1, 2, 3, 4, and 7 (P < 0.05). In the third month, the results showed a significant difference in terms of VSS (P = 0.005). Topical TG, due to its favorable effects on wound healing and pain reduction, can be administered as a therapeutic agent in patients with a skin graft.

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.

Pentoxifylline (PTX) has broad-spectrum properties such as anti-inflammatory, anticoagulant, and antiviral effects. The aim of this study was to evaluate the efficacy and safety of PTX in hospitalized patients with COVID-19. This double-blind, placebo-controlled randomized clinical trial was conducted on hospitalized patients with COVID-19. The recruited patients were randomly (1:1) assigned to the PTX group and the placebo group. The intervention group received PTX capsules at a dose of 400 mg three times a day for 10 days along with the national regimen, including interferon plus lopinavir/ritonavir and hydroxychloroquine. The primary outcome was the improvement of clinical scores. The secondary outcomes, on the other hand, were improvement in inflammatory and oxidative stress factors and hospital complications. From a total of 102 patients who met the inclusion criteria, 72 individuals completed the study and were analyzed. No significant differences were shown in demographics and baseline clinical characteristics. Clinical scores was not significant between the two groups (P = 0.31 and 0.07 for day 5 and 11, respectively). Although the mean serum levels of interleukin-6 (IL-6) and glutathione changed significantly after 5 days in the PTX group (P = 0.03 and p = 0.04), ICU admission, intubation, and hospital stay did not differ between the two groups. The results of our study did not show any superiority of PTX over placebo in improving the clinical outcomes of patients with COVID-19. Although PTX had a beneficial effect on IL-6 and showed an acceptable safety profile, it did not offer any clinical benefit for COVID-19 complications.

This study aimed to assess the additive value of olanzapine to a combination of ondansetron and dexamethasone to prevent chemotherapy-induced nausea and vomiting (CINV) in pediatric patients. A total of 40 patients between 4 to 18 years of age were enrolled in this randomized clinical trial. Both groups received a combination of ondansetron and dexamethasone, and 0.14 mg/kg olanzapine or matched placebo were administered for olanzapine and control groups, respectively. The primary end points were complete response and lack of nausea as far as three days after chemotherapy evaluated by the Common Terminology Criteria for Adverse Effects (CTCAE) v5.0 and the Multinational Association of Supportive Care in Cancer (MASCC) Anti-emesis Tool (MAT). Side effects of olanzapine were also analyzed. In patients receiving the standard regimen of ondansetron and dexamethasone, nausea was observed in 10.5% and 21% of patients according to MAT and CTCAE scales, respectively. In the olanzapine group, 37.5% (MAT scale) and 31.3% (CTCAE scale) of patients developed nausea. Complete response was observed in 84% (MAT scale) and 94.7% (CTCAE scale) of patients in the placebo group receiving ondansetron and dexamethasone. In comparison, it was observed in 87.5% (MAT scale) and 81.25% (CTCAE scale) for patients allocated to the olanzapine group. Neither acute nor delayed CINV was statistically different between placebo and olanzapine groups. The frequency of adverse effects was higher in the olanzapine group. Adding olanzapine to the standard regimen of CINV prophylaxis was only unhelpful in pediatric patients receiving moderately emetogenic chemotherapy but also associated with a higher rate of minor side effects.

Aim: The aim of this study was to evaluate the efficacy and side effects of silymarin in the treatment of CIPN. Methods: Patients who referred to outpatient oncology department of a referral educational hospital affiliated to Mazandaran University of Medical Sciences and experienced CIPN were randomized to receive silymarin or placebo. Intervention group received 140 mg of the Silymarin twice daily accompanied and 300 mg/day Gabapentin, whereas control group received 300 mg/day of Gabapentin and placebo twice daily for 3 months. The grade of neuropathy was determined according to the CTCAE criterion. The improvement of neuropathy was defined as the reduction of at least one neuropathic score. The visual analogue scale (VAS) was used to assess the severity of patients’ pain and the EORTC-QLQ-C30 criterion was used to assess the quality of life. Patients were evaluated initially and at the follow up visit 3 months after the enrollment. Results: A total of 80 patients were enrolled in the study. There was no significant difference between the groups in terms of severity of neuropathy at baseline. At the end of the study, the number of people with improved neuropathy in the silymarin group was 82.8% patients, which was significantly higher than 48.4% observed in the patients received placebo (P= 0.005). The silymarin-treated group showed a significant reduction in pain compared with those receiving placebo. Despite the improvement in quality of life in the intervention group compared to the comparison group, this difference was not statistically significant. Gastrointestinal symptoms were the only reported side effects with a similar incidence in two groups. Conclusion: The present data demonstrate the potential clinical use of silymarin as an adjuvant therapy to reduce CIPN symptoms.

Objectives: Despite extensive caffeine use in preterm infants, the pharmacokinetics (PKs) data are limited because of the studies are complicated to do in these patients. This research was investigated the PK profile of two various dosages of caffeine in premature neonates. Materials AND METHODS: The PK values of caffeine in premature neonates with Apnea were predicted by using all of computer-based simulation (Simcyp®), population-based PK, and modeling (P-Pharm®). We assayed the plasma levels of caffeine in two groups. The information was analyzed utilizing nonlinear mixed-effects modeling approach. The PK parameters were assessed simulating virtual clinical considers with subjects got 20 mg. kg−1 of caffeine in both groups, which was followed by a 5 mg. kg−1 once daily in Group 1 or 2.5 mg. kg−1 twice daily in Group 2. All statistical analysis was executed utilizing SSPS issue 19 and a P value of 0.05 was chosen significance. Results: In the present study, the means CL, volume of distribution, and T1/2 of caffeine in preterm infants were 0.0476 L. h−1, 1.1081 L, 16.2284 h, respectively. Whereas our simulated means by Simcyp were 0.090 L. h−1, 1.841 L, and 14.653 h in Group 1 and 16.223 h in Group 2, respectively. Conclusions: There was overall good agreement between predicted and measured PK values in our study. This study provides an initial demonstration of Simcyp simulation advantage on anticipating of PK parameters.

Background and aim This study examined whether administration of amlodipine could improve myocardial iron loading status in patients with transfusion dependent β-thalassemia (TDT), through a placebo-controlled, crossover study. Methods Amlodipine (5 mg, daily) or placebo were prescribed to all patients (n = 19) for 6 months, and after a 2-week washout period, patients were crossed over to the other group. The efficacy of amlodipine on iron loading was assessed by measuring myocardial T2*-weighted magnetic resonance imaging (MRI T2*, millisecond [ms]) and serum ferritin (ng/mL). Results Seventeen patients completed the study. The mean ± standard deviation [SD] of myocardial MRI T2* at baseline was 9.83 ± 2.67 ms Myocardial MRI T2* value rose to 11.44 ± 4.14 ms post amlodipine treatment in all patients. After placebo, myocardial MRI T2* value reached 10.29 ± 4.01 ms After controlling the baseline measures, Hedges's g for ferritin and myocardial MRI T2* outcomes were estimated 3.84 (95% confidence interval [CI] 2.68 to 4.97) and -1.80 (95% CI -2.58 to -0.10), respectively. Conclusion Amlodipine might improve myocardial MRI T2* and serum ferritin level compared to placebo. However, larger clinical studies are needed to confirm the results.

Introduction: Leptospirosis is an important zoonotic disease in paddy field with 29.5% prevalence rate in Mazandaran province and 4% to 52% mortality rate among hospitalized patients. Prevention is an important strategy for the control of this disease. This study aimed to compare the prophylactic effect of azithromycin versus doxycycline against leptospirosis in an endemic area in north of Iran. Methodology: In this randomized double-blind placebo-controlled trial, paddy field workers (n = 187) were randomized to receive azithromycin (500mg weekly), doxycycline (200 mg weekly) or placebo starting one week before exposure to paddy field, during and to four weeks after. Paddy field workers aged 18- 65 years who signed the informed consent form were assessed for signs and symptoms of leptospirosis in addition to serologic evidence of the disease 6th and 12th week. Data were analyzed with SPSS version 13 using Chi-square and Fisher exact test and ANOVA. Results: From June to September 2016, 187 participants were entered the study to receive azithromycin (n = 66), doxycycline (n = 71) or placebo (n = 50). In terms of preventing against clinical leptospirosis, there was not any significant difference between three arms, though there was statistically significant difference of seropositivity after 6 and 12 weeks in comparison to baseline among all three groups (P = 0.029) and between active treatment (eg. azithromycin and doxycycline) groups and placebo group (P = 0.01). Conclusion: Azithromycin like doxycycline decreased seropositivity without significant effect on clinical leptospirosis.

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.

Chronic myeloid leukemia (CML), a myeloproliferative disorder, is caused by overactivity of BCR-ABL1 (breakpoint cluster region-Abelson) has been successfully treated by Tyrosine kinase inhibitors (TKIs). While imatinib is known as the first-line treatment of CML, in some cases other TKIs including dasatinib, nilotinib, bosutinib, and ponatinib may be preferred. Dasatinib, a second-generation TKI, inhibits multiple family kinases including BCR-ABL, SRC family kinases, receptor kinases, and TEC family kinases. It is effective against most imatinib-resistant cases except T315I mutation. Despite the superiority of dasatinib in CML hematologic and cytogenetic responses compared to imatinib, its potentially harmful pulmonary complications including pleural effusion (PE) and pulmonary arterial hypertension (PAH) may limit its use. Appropriate management of these serious adverse reactions is critical in both improving the quality of life and outcome of patients. In this narrative review, we will scrutinize the pulmonary complications of dasatinib and focus on the management of these toxicities.

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.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 p0.05.The patients' age enrolled in this study are from 21 to 75 years with a mean and standard deviation of 48.6±14.0. The male to female ratio in our participants was 54/21. Fever was the most common symptoms in 66 (88.0%) patients, followed by myalgia in 62 (82.7%) cases. The level of interleukin 10 was significantly higher in severe illness (P=0.003) and fatal cases (p0.028) compared with recovered patients. The level of TNF-α level was also higher in the severe illness and Weil's syndrome compared with the mild kind (P=0.022).Our results showed that the levels of TNF-α and IL-10 significantly increased in severe leptospirosis. Also, IL-10 was significantly higher in fatal cases. The inhibition of IL-10 production might play an important role in decreasing the risk of fatal outcomes in leptospirosis.

PURPOSE/BACKGROUND It is well documented that one of the pathophysiological mechanisms of negative symptoms in patients with schizophrenia is hypofunction of N-methyl-d-aspartate receptors. This double-blind, placebo-controlled clinical trial was designed to assess the efficacy and safety of nanocurcumin as an adjuvant agent on psychotic symptoms, especially negative symptoms, in patients with chronic schizophrenia. METHODS/PROCEDURES Fifty-six inpatients with stable chronic schizophrenia and predominant negative symptoms were randomized in a 1:1 ratio to nanocurcumin soft gel capsule (160 mg/d) and control groups, along with their antipsychotic regimen for 16 weeks. The efficacy of treatment was assessed by Positive and Negative Syndrome Scale, Calgary Depression Scale for Schizophrenia, Clinical Global Impressions-Severity, and Clinical Global Impressions-Improvement scales. Extrapyramidal symptoms were evaluated by Simpson-Angus Scale and Barnes Akathisia Rating Scale. Patients were assessed at baseline and weeks 4, 8, 12, and 16 after the medication started. FINDINGS/RESULTS No significant differences were observed in demographic or clinical variables between both groups at baseline. The nanocurcumin group showed significantly greater improvement on the negative subscale (P = 0.05), the general psychopathology subscale (P < 0.001), the positive subscale (P = 0.004), total Positive and Negative Syndrome Scale (P < 0.001), Clinical Global Impressions-Severity (P < 0.001), and Clinical Global Impressions-Improvement scores (P < 0.001) in comparison with the control group at the endpoint. Extrapyramidal symptom rating scales and Calgary Depression Scale for Schizophrenia and frequency of other adverse effects were comparable between 2 groups. IMPLICATIONS/CONCLUSIONS The present study indicates nanocurcumin as a safe and potential adjunctive treatment strategy for treatment of primary negative symptoms of schizophrenia.

Background The aim of this clinical trial was to evaluate the effects of febuxostat (FBX) in comparison with hydroxychloroquine (HCQ) on clinical symptoms, laboratory tests and chest CT findings in outpatients with moderate symptoms of COVID-19 infection. Methods We conducted a clinical trial involving adult outpatients with the moderate respiratory illness following COVID-19 infection. Patients were randomly assigned to receive either FBX or HCQ for 5 days. The measured variables were needs to hospitalisation, clinical and laboratory data including fever, cough, breathing rate, C-Reactive Protein level, lymphocytes count at onset of admission and was well as at 5 days of treatments. In addition, CT findings were evaluated on admission and 14 days after initiation of treatment. Results Sixty subjects were enrolled in the study with a 1 to 1 ratio in FBX and HCQ groups. On admission, fever (66.7%), cough (87%), tachypnoea (44.4%), dyspnoea (35%), elevated CRP value (94.4%) and lung involvement according to chest CT (100%) were documented in enrolled patients with insignificant difference between FBX and HCQ groups. Fever, cough and tachypnoea were significantly mitigated in both groups after five days of treatments without any significant differences between groups. The mean percentages of lung involvement were significantly reduced to 7.3% and 8% after 14 days of treatment with FBX and HCQ, respectively. In adult outpatients with moderate COVID-19 infection, the effectiveness of FBX and HCQ was not different in terms of resolution of clinical manifestations, laboratory tests and lung CT findings. Conclusion This trial suggests that FBX is as an alternative treatment to HCQ for COVID-19 infection and may be considered in patients with a contraindication or precaution to HCQ.

Aims: The aim of this double-blind randomized clinical trial was to determine the effects of FBX in comparison with hydroxychloroquine (HCQ) on clinical symptoms, laboratory tests and chest CT findings in patients with COVID-19-causing moderate symptomatic disease. Methods: We conducted a randomized, double blind clinical trial involving adult outpatients’ patients with COVID-19 infection, which causes the moderate respiratory illness. Sixty patients were randomly assigned to receive either FBX or HCQ for 5 days. The measured variables were clinical and laboratory data including rate of fever, cough, berating rate, C-Reactive Protein level, lymphocytes count at onset of admission and was well as at 5 days of treatments. In addition, CT lesions were evaluated on admission and 14 days of treatments in both groups. Results: Fever, cough and tachypnea significantly mitigated in both groups after five days of treatments. The lymphocytes count significantly increased in both treatment groups and the CRP values were dropped in normal range (negative) in major of patients receiving FBX or HCQ treatment. It was not observed any significantly difference between FBX and HCQ in frequency of these symptoms. The mean percentages of CT abnormality scores were significantly reduced to 7.3% and 8% after 14 days of FBX and HCQ treatments, respectively. In adult outpatients with moderate symptomatic Covid-19, the effectiveness of FBX was same to HCQ in improvement of clinical manifestations, laboratory tests and CT lesions. Conclusion: These findings suggest FBX as an alternative treatment for Covid-19 infection in patients with contraindication or precaution to HCQ.

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 p = 0.001). The median lifestyle score improved significantly with Aloe vera during RT (p p = 0.009). Conclusion This study showed that Aloe vera topical ointment was effective in prevention of symptoms of ARP in patients undergoing RT for pelvic cancers. Trial registration IRCT201606042027N6. Registration date: 2016-09-04.

Background Acute radiation proctitis (ARP) is a common complication of radiation therapy (RT). This adverse effect in severe cases ultimately results in interruption of RT and poor outcome. Aloe vera contains multiple antioxidant and anti-inflammatory compounds This study was aimed to evaluate the preventive effects of Aloe vera in ARP in colorectal cancer.Method: twenty eligible colorectal cancer patients, who received radiation, were randomized to receive Aloe vera 3% ointment or placebo for six weeks. At each weekly visit, ARP symptoms were evaluated by Radiation Therapy Oncology Group (RTOG) and clinical presentation criteria. The lifestyle impact of the symptoms, depression and anxiety for assessment of psychosocial status of patients, and quantitative CRP were evaluated as secondary endpoints.Results there was a significant improvement in the symptom index for diarrhea and total RTOG scores and quantitative CRP levels (between-subject differences or group effect) (p Aloe group. The overall time trend (within-subject differences or time effect) was statistically significant for rectal bleeding, rectal pain, total clinical scores, proctitis, cystitis, and total RTOG (P Aloe vera group. The median lifestyle score improved significantly with Aloe vera. Intervention patients had a lower probability of presenting anxiety in their overall HAD scale during RT.Conclusion The use of topical formulation of Aloe vera 3% diminished the severity of ARP in colorectal cancer patients. Trial registration: Current Controlled Trials IRCT201606042027N6, registrations date: 2016-04-09.

Purpose Taxane-induced peripheral neuropathy (TIPN) is a common and bothersome toxicity. This study aimed to determine the incidence and severity of TIPN in patients with breast cancer and to investigate the relationship between TIPN and quality of life. Methods A total of 82 breast cancer patients with TIPN symptoms were included in this study. The criteria of National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE v4.03) and the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30, version 3.0) were used to evaluate grading of sensory neuropathy and quality of life, respectively. Analysis of the data was done by IBM SPSS statistics version 23. Results A total of 346 patients received taxane-based chemotherapy and 82 patients (23.7%) experience TIPN. The mean (SD) global health status/quality of life, physical functioning, role functioning, and pain subscales were 60.63 (5.26), 80.64 (9.05), 81.77 (10.41), and 43.88 (11.27), respectively. There were significant negative correlations between global health status/quality of life, physical functioning, and role functioning subscales with the grade of neuropathy (r = −0.33, −0.80, and −0.61, respectively) and positive correlation between pain subscale and the grade of neuropathy (r = 0.70). Conclusion This study shows a clear association between TIPN and worsened quality of life. These findings emphasize on detecting and management of TIPN in an effort to improve the quality of life of breast cancer patients.

Taxane-induced peripheral neuropathy (TIPN) is a main toxicity of taxanes with no effective treatment. This study aimed to compare the efficacy and safety of pregabalin (150 mg daily) and duloxetine (60 mg daily) for managing TIPN in breast cancer patients. This randomized, double-blind, Phase II clinical trial was carried out at a chemotherapy center affiliated to Mazandaran University of Medical Sciences. Patients with breast cancer who received paclitaxel or docetaxel and had a grade 1 or more neuropathy (based on the National Cancer Institute Common Terminology Criteria for Adverse Events version (NCI-CTCAE v4.03), and who had score 4 or higher neuropathic pain severity [based on the visual analog scale (VAS)] were enrolled. Response to treatment was assessed based on improvements in the VAS, NCI-CTCAE, and Patient Neurotoxicity Questionnaire (PNQ) scores during a 6-week trial. Both interventions were effective in decreasing TIPN compared to baseline. At Week 6, the VAS scores were improved in 37/40 (92.5%) and 16/42 (38.1%) of the patients in the pregabalin and duloxetine groups, respectively (p

Acute radiation proctitis (ARP) is a common side-effect that affects up to 50% of patients receiving radiotherapy. The aim of this study was to evaluate the role of a topical preparation of Aloe vera in the treatment of ARP induced by radiotherapy of pelvic area.In this double-blind placebo-controlled trial, 20 consecutive patients with ARP after external-beam radiation therapy (46-72 Gy) of pelvic malignancies were randomized to receive either Aloe vera 3% or placebo ointment, 1 g twice daily for 4 weeks. These patients presented with at least two of the following symptoms: rectal bleeding, abdominal/rectal pain, diarrhea, or fecal urgency. These symptoms were rated by the patients in terms of their severity (grade 0-4) for each of the symptoms mentioned earlier at baseline and then weekly for 4 weeks. A symptom index was calculated by the addition of the scores (16 most symptomatic). Radiation Therapy Oncology Group (RTOG) acute toxicity criteria and psychosocial status of the patients were also recorded weekly. The lifestyle impact of the symptoms was assessed by questionnaire grading from 0 (no effect on daily activity) to 4 (afraid to leave home).There was a significant (p 0.05) improvement in the symptom index (before treatment vs. after treatment with Aloe vera) for diarrhea (median score: 0.67 vs. 0.11), fecal urgency (median score: 0.89 vs. 0.11), clinical presentation total (median score: 4.33 vs. 1.22), RTOG total (median score: 2.89 vs. 0.89), and lifestyle (median score: 1.1 vs. 0.33). Hemorrhage and abdominal/rectal pain did not improve significantly. The odds ratios for advantage of Aloe vera over placebo for "clinical presentation total" and "RTOG total" were 3.97 (1.3-11.9) and 5.9 (1.6-21.6), respectively.A substantial number of patients with radiation proctitis seem to benefit from therapy with Aloe vera 3% ointment.

The aim of this study was to evaluate the usage of mometasone furoate nasal spray in the recovery of patients with severe microsmia or anosmia induced by COVID-19. This was a prospective clinical trial on non-hospitalized adult patients with COVID-19 (>18 years) who had severe microsmia or anosmia within two weeks. The subjects were randomly assigned to the mometasone furoate group (100 mcg twice daily) or sodium chloride group (0.9%); both groups also received olfactory training for 4 weeks. The primary outcome was the improvement of the olfactory score at the end of the study. Visual analog scale (VAS) and the University of Pennsylvania Smell Identification Test (UPSIT) were used to assess primary outcome. A total of 80 patients were recruited, 77 of them completed the study and were analyzed. There was no statistically significant difference in terms of demographics and baseline clinical characteristics. The olfactory scores (based on VAS) at weekly intervals showed a significant difference between the two groups (P:0.318, 0.239). However, a significant between-group difference was noted in the severity of loss of smell (P

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

Traumatic brain injury (TBI) is a public health problem worldwide. Secondary damage of brain injury begins within a few minutes after the trauma and can last a long time. It can be reversible, unlike primary injury. Therefore, therapeutic intervention can be used. The aims of this study were to assess the effects of minocycline on neurological function and serum S100B protein and neuron-specific enolase (NSE) levels in patients with moderate to severe TBI. Patients with acute onset of TBI and surgical evacuation of hematoma were randomized to receive either minocycline 100 mg orally twice daily or placebo for 7 days. The primary outcomes included changes in level of S100B and NSE at different time points during the trial. Additionally, changes in Glasgow coma scale (GCS) score were evaluated. The Glasgow Outcome Scale-Extended (GOS-E) score at 6 months after injury was assessed in discharge patients. Thirty four patients were randomized into the placebo (n = 20) and treatment (n = 14) groups. There was a marginal statistically significant differences in the normalized value of S100B between groups (p < 0.1). The reduction in serum NSE level from baseline to day 5 was statistically significant (p = 0.01) in minocycline group while it was not significantly decrease in placebo group (p = 0.2). Also, GCS improvement over time within the minocycline group was significant (p = 0.04) while was not significant in placebo group (p = 0.11). The GOS-E scores were not significantly different between minocycline and placebo group. Based on this study, it seems that the use of minocycline may be effective in acute TBI.

Gastric cancer is the fourth common cancer and the second leading cause of cancer death worldwide. Due to lack of adequate information on the side effects of chemotherapy regimens in treatment of gastric cancer, this study was aimed to determine the side effects of two common chemotherapy regimens of gastric cancer. This prospective study was conducted in Emam Khomeini Educational Hospital and Touba Polyclinic; both are affiliated to Mazandaran University of Medical Sciences. The frequency and severity of side effects of chemotherapy were recorded based on the National Cancer Institution (NCI) Toxicity Criteria (version 2). DCF (Docetaxel, Cisplatin, 5FU) and FOLFOX (Folinic acid, 5FU, Oxaliplatin) adverse reactions were compared using SPSS 16 software. One hundred twenty five chemotherapy cycles administered to seventy four patients were assessed. The most common used regimens were DCF (70%) and FOLFOX (16%). The incidence of vomiting was higher with DCF compared to FOLFOX (P = 0.049). In more than 50% of cycles, DCF regimen caused diarrhea, while in FOLFOX regimen it was less than 9% (P = 0.002). Stomatitis, visual changes, nausea, skin reactions, and constipation were not significantly different between the two regimens. It seems that the adverse drug reactions of FOLFOX regimen were more favorable than DCF regimen. The results of this study may help clinicians choosing a more favorable chemotherapy regimen especially in patients with a low performance status who have difficulties in tolerating a chemotherapy regimen with a more severe adverse effect profile.

Background: Coronary artery bypass graft surgery (CABG) may cause a substantial decrease in trace elements of whole blood during the operation, as well as increased oxidative stress and result in lung damage. Objectives: This study aimed to evaluate the effect of Addamel, as a complete mixture of trace elements, in reducing the period of mechanical ventilation following the cardiac surgery. Methods: In this randomized, double-blind, placebo-controlled trial, two hundred patients receiving CABG were randomized to receive three doses of either Addamel or normal saline. Selenium, zinc, copper, ferrous, and manganese serum levels were measured before the operation, on days one and two in all groups. Besides, the effects of Addamel on the mechanical ventilation period were evaluated. Results: The mean length of stay on the mechanical ventilator was lower in the supplemented patients (21.98 ± 8.4 days) than the control patients (25.16 ± 8.44 days), and the difference was statistically significant (P = 0.009). Conclusions: A substantial number of patients undergoing CABG may benefit from supplementation with Addamel, as a source of trace elements.

There is controversy regarding the efficacy of tamoxifen in breast cancer patients who are carriers of cytochrome P450 2D6 (CYP2D6) gene polymorphisms. Poor metabolizer genotypes may not fully convert tamoxifen to its active metabolite endoxifen and thus have less exposure to anti-estrogen therapy. The present study was conducted to identify the prevalence of CYP2D6 genotypes among Iranian breast cancer patients. A total of 84 estrogen receptor-positive breast cancer patients treated at a referral center in the north of Iran were examined. A peripheral blood sample was obtained from each patient to determine the presence of *3, *4, *10 and *17 single nucleotide polymorphisms of the CYP2D6 gene by polymerase chain reaction-based restriction fragment-length polymorphism analysis. Of the four genotypes assessed, CYP2D6*4 was the most common variant and was identified in 41 (48.8%) patients as heterozygous (G/A) and 3 (3.6%) as homozygous (A/A) alleles. CYP2D6*10 heterozygous mutated alleles (C/T) were also a common genotype that presented in 22 (26.2%) of the study subjects. Variant *17 was less common and was detected only as heterozygous (C/T) in 3 patients (3.6%). No CYP2D6*3 heterozygous or homozygous mutated alleles were observed. In conclusion, the frequency of the CYP2D6 nonfunctional alleles *4 and *10 appeared relatively high in Iranian patients with hormone-sensitive breast cancer. This finding may affect the selection of an optimal hormone therapy, as patients with low CYP2D6 pathway activity may not sufficiently convert tamoxifen to its active metabolite endoxifen.

The present study aimed to evaluate the effectiveness of Nigella sativa L. (N. sativa) extract on preventing the incidence of acute radiation dermatitis (ARD) in breast cancer patients.Sixty-two breast cancer patients undergoing radiotherapy (RT) were randomly assigned to receiveN. sativa 5% gel or placebo. Patients were instructed to apply the medications twice daily during RT period. The severity of ARD, the incidence of moist desquamation, worst experienced pain, and skin-related quality of life (SRQOL) scores were assessed weekly during RT.Patients who were treated with the N. sativa gel developed ARD significantly less frequently compared to those who used the placebo (p 0.05 for all weeks except week 2, p = 0.36). The incidence time of grade 2 and 3 of Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer (RTOG/EORTC) toxicity was prolonged significantly with N. sativa gel as compared to placebo (35 vs. 29 days, p = 0.00 and 42 vs. 40 days, p = 0.01, respectively). Furthermore, the occurrence of moist desquamation was delayed in the N. sativa gel group compared with the placebo group (37 vs. 33 days, p = 0.01). The mean score of the worst pain that patients experienced in the placebo group was significantly higher than that of the N. sativa gel group at week 3 (2.5 ± 0.5 vs. 1.2 ± 0.3, p 0.05). Nonetheless, the application of N. sativa gel had no significant effect on the SRQOL of patients at any week.N. sativa extract significantly decreases the severity of ARD and delays the onset of moist desquamation in breast cancer patients.

The purpose of this randomized, placebo-controlled, double-blind study was to investigate the preventive effect of topical administration of atorvastatin (ATV) on the acute radiation-induced skin toxicity in patients with breast cancer. Seventy breast cancer patients were randomly assigned to use topical ATV 1% or placebo gels during radiotherapy twice daily. Radiation-induced dermatitis was classified according to the radiation therapy oncology group (RTOG) criteria, as well as pain and itching were scored according to VAS (visual analogue scale) for 6 weeks of treatment. Topical administration of ATV gel during radiotherapy reduced significantly radiation-induced breast swelling, itching, and pain in breast cancer patients by factors of 1.8, 1.7, and 1.5, respectively. ATV reduced the redness caused by radiotherapy in patients as compared with placebo; however, this difference was statistically not significant. ATV was able to reduce significantly itching, breast edema, and pain in patients during radiotherapy.

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.

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.

Previous studies reported promising efficacy for celecoxib in the treatment of cancer cachexia. We designed this study to test the hypothesis that combination therapy with megestrol acetate (MA) plus celecoxib is superior to MA alone. Ninety eligible gastrointestinal cancer patients randomly received either MA 320 mg/day plus placebo (arm1) or MA 320 mg/day plus celecoxib 200 mg/day (arm2). Patients were evaluated at baseline, then 1 and 2 months after starting interventions. The primary outcome was body weight. Secondary outcomes were quality of life, grip strength, appetite score, performance status, plasma albumin, CRP, IL-6, and Glasgow Prognostic Score. Patients were comparable at baseline. Sixty patients were assessable for the first month and 33 patients for the second month. After 2 months, patients in arm1 (MA + placebo) and arm2 (MA + celecoxib) experienced 4.0 ± 3.4 and 2.2 ± 3.6Kg of weight gain respectively (P = 0.163). Changes relative to baseline were statistically significant in both arms of the study (P = 0.001). Regarding secondary outcomes, comparisons between groups did not show any statistically significant difference, but within-group changes were significant in both arms of the study. Since both MA alone and MA plus celecoxib are associated with improvement of cachexia in GI cancer patients, this study failed to show that adding celecoxib (200 mg/day) to megestrol (320 mg/day) could enhance anti-cachexic effects of megestrol.

This study aimed to determine the potential iron-chelating effects of silymarin in patients with β-thalassemia major receiving standard iron-chelation therapy. We evaluated whether addition of silymarin to standard iron-chelation therapy could improve iron burden markers and liver and cardiac function in these patients, via a placebo-controlled, crossover clinical study. Silymarin (140 mg) or placebo were administered thrice daily to all patients (n = 82) for 12 weeks, and after a 2-week washout period, patients were crossed over to the other groups. Silymarin efficacy was assessed by measuring serum iron level, ferritin level, total iron-binding capacity and liver and cardiac function on magnetic resonance imaging. Silymarin treatment resulted in a negative change in the serum iron and ferritin levels and a positive change in the total iron-binding capacity levels (treatment effect, p < .001, p = .06, and p = .05, respectively). Silymarin treatment led to positive changes in cardiac and liver function in both treatment sequences of study; however, this was not statistically significant. There was a negative change in liver iron concentration in both treatment sequences (treatment effect, p = .02). In conclusion, combined iron-chelation and silymarin therapy was effective for improving the iron-burden status in patients with β-thalassemia major.

Background & aims Blood transfusion therapy is lifesaving for individuals with β-thalassemia major (β-TM). Iron burden following blood transfusion is the main cause of oxidative stress (OS) and organ dysfunction in these patients. The aim of this study was to evaluate the effects of silymarin on serum antioxidant and oxidative status in patients with β-TM. Methods A crossover, randomized controlled trial was performed on 82 thalassemia patients. In two periods of 12 weeks, patients received 420 mg silymarin (divided into three equal 140-mg daily doses) and placebo. The washout period between the two phases was two weeks. Serum malondialdehyde (MDA), protein carbonyl (CO), total antioxidant capacity (TAC), and reduced glutathione (GSH) were measured before and after both periods. Results Sixty-nine patients completed the study. Mean serum MDA and protein CO significantly decreased in all patients with β-TM after three months of treatment with silymarin. At the end of the study, serum MDA decreased from 20.36 ± 20.11 to 4.79 ± 4.71 μmol/l (compared to 17.81 ± 16.05 μmol/l after administration of placebo), and protein CO dropped from 0.31 ± 0.28 to 0.11 ± 0.09 mM/l (compared to 0.24 ± 0.17 mM/l with placebo). Additional laboratory parameters (such as serum TAC and plasma GSH) were also significantly elevated after therapy with silymarin. At the end of the study, serum TAC increased in all patients from 620.7 ± 202.64 to 971.83 ± 328.16 μmol FeSO4/l (compared to 672.22 ± 206.88 μmol FeSO4/l with placebo), and GSH increased from 46.16 ± 41.68 to 195.35 ± 210.98 nM/l (compared to 58.52 ± 48.95 nM/l with placebo). The treatment effect of silymarin was measured using a mixed-effects model of variance analysis for changes in MDA, protein CO, TAC, and GSH, with significant effects being demonstrated for each laboratory parameter (P Conclusions Silymarin was effective in decreasing serum OS and enhancing serum antioxidant capability in patients with β-thalassemia major. Silymarin given as an adjuvant therapy to standard iron chelators may provide an improvement in the OS measurements obtained in these patients, with accompanying benefit.

Background: Differential diagnosis of systemic inflammatory response syndrome (SIRS) with or without infectious cause is critically important in terms of initiating antimicrobial agents in case of infectious etiology such as ventilator-associated pneumonia (VAP). The aim of this study was to determine the diagnostic and prognostic roles of C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) in differentiating between ventilator-associated pneumonia and SIRS without infectious etiology. Materials and Methods: In this prospective observational study, 91 adult intensive care unit (ICU) patients were enrolled. According to established diagnostic criteria, they were classified into three groups of “non-SIRS non-VAP”, “SIRS non-VAP” and “SIRS-VAP”. Serum CRP and TNF-α were measured on days 1, 3 and 7 of the study and compared using repeated measures ANOVA. Results: With respect to diagnosis, there was no significant difference in the values of these biomarkers between groups (P>0.05). There was no statistically significant “time trend” for C-reactive protein and TNF-α (P>0.05). Considering both group effect and Time effect, the changes were not significantly different for CRP (P= 0.86) and TNF-α (P=0.69). In contrast, the clinical score and the clinical pulmonary infection score (CPIS) ≥ 6, had 100% specificity for diagnosing VAP. With respect to prognosis, only an unchanged or decreasing TNF-α from day 1 to day 3 was marginally associated with 28-day survival. However, day 1 and day 3 acute physiology and chronic health evaluation II (APACHE II) scores were highly associated with 28-day survival. Conclusion: Unlike clinical scoring system including CPIS and APACHE II, TNF-α and CRP levels were not useful as diagnostic or prognostic biomarkers for differentiating between SIRS with VAP etiology and SIRS without infectious etiology.

Acute Venous Thromboembolism (VTE) is a common disease associated with the significant morbidity and mortality. We reviewed clinical outcomes systematically with Dabigatran as a direct oral anticoagulants (DOAC) for treatment of acute VTE. We used Ovide, PubMed, Cochrane (CENTRAL), EMBASE, Scopus, Science Direct, LILAC(for article written not English) and also Iranian database; Magiran, Isc, Iran Medex, Iran DOC, Doaj up to May 2014 to identify randomized clinical trials of Dabigatran compared with conventional treatment for VTE. Two investigators extracted data independently. Number of 5107 patients including two trails were selected. The risk of recurrent VTE was similar with the Dabigatran and standard treatment (Hazard Ratio, 95% confidence interval 1.09 (0.76-1.57). Dabigatran reduced the risk of minor bleeding in comparison with standard treatment; Warfarin (0.62) (0.50-0.76). Finally-in minor bleeding-the Dabigatran seemed as effective as, and probably safer than standard treatment of acute VTE. But in some aspects such as adherence to treatment, pregnant patient, impact on quality of life, new researches are needed to be clarified.

A suitable pharmacological substitute for the well-established surgical delay technique for random skin flaps to increase viability has been elusive.To evaluate the effects of nitroglycerin and botulinum toxin type A on random flap survival in a rat model.The present controlled experimental study was performed in the four groups of rats. One week after intervention in each group, the flap was raised and kept in situ, and flap necrosis was evaluated through follow-up. Group 1 received intradermal botulinum toxin type A (BTX-A) and topical nitroglycerin 2%; group 2 received BTX-A and topical Vaseline (Unilever, USA); group 3 received topical nitroglycerin and intradermal normal saline; and group 4 received topical Vaseline and intradermal normal saline.BTX-A reduced the area of necrosis compared with control (24% versus 56% respectively; P0.001). Nitroglycerin application was associated with a trend toward improved flap viability (42% versus 56%; P=0.059). The combination of topical nitroglycerin and BTX-A, compared with Vaseline and BTX-A, was associated with decreased flap necrosis (16.1% versus 24%, respectively), although it was not statistically significant (P=0.45).BTX-A was effective in reducing distal flap necrosis. The effect of BTX-A was significantly more pronounced than nitroglycerin ointment.Il n’existe aucun substitut pharmacologique convenable pour remplacer la technique d’autonomisation bien établie visant à accroître la survie des lambeaux cutanés.Évaluer les effets de la nitroglycérine et de la toxine botulique de type A (BTX-A) sur la survie de lambeaux sans dissection pédiculaire dans un modèle de rat.Les chercheurs ont réalisé la présente étude expérimentale contrôlée auprès de quatre groupes de rats. Dans chaque groupe, une semaine après l’intervention, ils ont prélevé le lambeau et l’ont conservéLa BTX-A réduisait l’aire de la nécrose par rapport à celle des sujets témoins (24 % au lieu de 56 %, respectivement; P0,001). L’application de nitroglycérine favorisait une meilleure viabilité du lambeau (42 % par rapport à 56 %; P=0,059). Par rapport à la Vaseline et à la BTX-A, la combinaison de nitroglycérine topique et de BTX-A s’associait à une diminution de la nécrose du lambeau (16,1 % au lieu de 24 %), même si ce n’était pas statistiquement significatif (P=0,45).La BTX-A a réussi à réduire la nécrose du lambeau distal. Elle avait beaucoup plus d’effet que l’onguent de nitroglycérine.

Majorβ-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 ofβ-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 fromSilybum marianumplant. 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 withβ-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.