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: Intracranial hemorrhage (ICH) is a devastating condition with a high mortality and morbidity rate. Neuroprotective agents protect surrounding brain tissue from the toxic effects of hematoma and can result in better outcomes. There is evidence demonstrating the neuroprotective benefits of melatonin in experimental animal models of ICH. Reduced melatonin levels have been reported in the intensive care unit (ICU) patients. The aim of this study was to evaluate baseline melatonin levels and pharmacokinetic profile of melatonin in ICH patients.
Methods: This was a randomized clinical trial in which 24 patients with non-traumatic ICH were divided into melatonin and control groups. Subjects in the melatonin group received 30 mg of melatonin for 5 days. Another group of 12 healthy volunteers also were recruited for the study. Baseline serum melatonin levels were measured for all groups. For the pharmacokinetic study, sampling intervals were 0.25, 0.5, 0.75, 1.5, 3, 6 and 10 hours after melatonin administration. Samples were analyzed using an HPLC system with fluorescence detection.
Results: Serum melatonin concentrations found to be decreased in all patients. Patients showed a significant increase in levels by the third day but still lower than healthy volunteers. By day 5, the melatonin group reaches melatonin levels, statistically similar to healthy volunteers, but the control group didn't reach normal levels even on the seventh day of study.
Conclusion: Our study suggests that monitoring melatonin levels and supplementing with exogenous melatonin can correct the reduced levels. Further studies focused on melatonin administration in ICH patients can be helpful in evaluating clinical outcomes in these patients.

Background: Previous studies have indicated that parathyroid hormone (PTH) has been linked to post-myocardial infarction (MI) development. The aim of this cross-sectional study was to evaluate the relationship between PTH level and heart failure due to post infarction remodeling during the first 72 hours of hospitalization.
Methods: Seventy patients with a diagnosis of acute MI (age ≥18 years, 22 females and 48 males) were enrolled. Patients were admitted to the Imam Raza Educational, Research and Treatment Center, Mashhad University of Medical Sciences, Iran between July 2014 to September 2015. We measured PTH and vitamin D level. Blood samples were taken after 24 hours and 72 hours.
Results: During the first 72 hours, the PTH level significantly increased in patients with Post-MI heart failure. 68% of the subjects had an inappropriate vitamin D level at the time of admission. Mean levels of vitamin D and PTH increased compared with the baselines (95% CI, 0.15 to 10.03, P: 0.044), (95% CI, 6.5 to 24.8, P:0.001) respectively.
Conclusion: Acute elevations of serum PTH levels increased early remodeling heart failure after MI. Serum vitamin D status was independent of high serum PTH level. Based on the current evidence, PTH excess may be a risk factor for heart failure, so early treatment and omitting risk factors are the most effective strategies for the patients with acute myocardial infarction.

Background: Kidney transplant patients usually take a combination of medications after transplantation; hence, medication safety becomes an important issue in order to maintain the new organ working properly. To evaluate the incidence and risk factors associated with potential drug-drug interactions (pDDIs) in hospitalized patients in Nephrology and Post-transplant wards to improve clinical management of pDDIs by a clinical pharmacist.
Methods: In this cross-sectional study, patients in Nephrology and Post-transplant wards were screened for pDDIs, using the interaction screening program Lexi-comp resource^®. After evaluating the detected pDDIs for clinical relevance, the intervention was performed through physicians or nurses for type D and X drug interactions. Intervention feedback, implemented recommendations, and any probable adverse drug reactions were documented.
Results: During the study, 399 patients (239 in nephrology and 160 in post-transplant wards) plus 6105 drug orders were evaluated, and a total of 3263 DDIs were identified; of them, 827 (23.5%) were determined to be D and X classifications, and a total of 89.97% of all hospitalized cases had at least 1 pDDIs. Factors that had the greatest influence on pDDI incidence included the number of drugs and the admitted wards. Patients in the post-transplant ward experienced 2.3 times more DDIs than those in the nephrology ward. In total, 78% of class X and D DDIs required intervention, of which 75% were accepted and implemented by the physicians and nurses.
Conclusion: Clinically relevant pDDIs are common in patients in Nephrology and Post-transplant wards, and pharmacists play a critical role in detecting and managing this medical problem in hospitalized patients.

Backgrounds: Several generic forms of enoxaparin were introduced to the market after expiring the patent of Clexane. But the main problem with generic forms is its bio-equivalency with brand form as a little difference in active ingredients characteristics, could led to significant clinical differences. For evaluating the efficacy of enoxaparin, it is recommended to measure its activity against Anti Xa. The aim of this study was comparison of Anti Xa Activity of Enoxan® versus Clexane ® in critically ill patients with prophylactic doses.
Methods: This was a cross over, open label, randomized prospective study which was performed between September 2016 and December 2017 in intensive care unit of Labbafinezhad hospital, Tehran, Iran. Thirty adult patients, who received enoxaparin for prophylaxis of thromboembolic events, were recruited. Subjects were subsequently randomized to one of the treatment sequences (Generic–brand or brand–generic). The generic drug was enoxaparin sodium 40 mg (4,000 IU anti-FXa/0.4 mL), manufactured by Ronakpharm, Iran; the brand drug was enoxaparin sodium 40 mg (Clexane® 4,000 IU anti-FXa/0.4 mL), manufactured by Sanofi, France.
Results: Anti-Xa activity was assessed with Stago kit. The anti-Xa activity between 0.2 and 0.5 U/mL was defined as prophylaxis. The average Anti-Xa activities of Clexan and Rolexan were 0.3±0.12 and 0.22±0.10, respectively which reveals statistically no significant difference (P: 0.35). Also Anti-Xa activity in 6 and 11 patients in Clexan and Rolexan groups were under 0.2 (P: 0.16).
Conclusion: Our study showed comparable efficacy of prophylactic doses between Clexan and Rolexan in critically ill patients. Further studies in different patient population are recommended.

Background: The choice of appropriate antibiotics to treat nosocomial infections requires knowledge of antibiotic resistance pattern in the hospitals. The aim of this study was to determine antimicrobial resistance patterns of common pathogens of nosocomial infections (pneumonia, UTI, bloodstream infection, wound infection) in a referral teaching hospital.
Methods: This cross-sectional study was conducted over a 6-month period. The pathogens isolated from biological samples of hospitalized patients with nosocomial pneumonia, UTI, bloodstream infection, or wound infection underwent antibiotic susceptibility testing by Kirby-Bauer method (disk diffusion test).
Results: Over the study period, 442 cases of infection were recorded. Pneumonia (n = 204, 46.2%) and UTI (n = 118, 26.7%) showed the most frequency followed by BSI (n = 71, 16.1%) and wound infection (n = 49, 11%). Acinetobacter baumannii was the most common pathogen of nosocomial pneumonia infection that showed the most susceptibility to colistin (100%). Escherichia coli, the most common pathogen of urinary tract infections, showed the highest sensitivity to colistin (100%). Staphylococcus epidermidis was the most common bloodstream infection pathogen that showed the most sensitivity to vancomycin (100%). Enterococcus spp., the most common pathogens of wound infection, had the most susceptibility to linezolid (100%).
Conclusion: Nosocomial infections in our hospital have high rate of resistance to antibiotics representing the importance of improvement in antibiotic use and infection control.

Drug reaction with eosinophilia and systemic symptoms syndrome (DRESS) is a delayed infrequent potentially life-threatening drug reaction. Fever, rash, lymphadenopathy, eosinophilia, and hepatic involvement are common features. Aromatic anticonvulsants and allopurinol are the most frequent causative agents. However, some cases of antivirals induced DRESS are available. In this review, we try to summarize studies of antiviral induced DRESS syndrome.  The data were collected by searching PubMed, Science Direct, Google Scholar, Scopus, Cochrane database systematic reviews, and Islamic World Science Citation Center (ISC). The Keywords used as search terms were “DRESS syndrome”, “drug-induced hypersensitivity reaction (DIHS)”, “antiviral”, and names of various antiviral agents. Finally, a total of 28 relevant articles up to the date of publication were included for review. Totally, 30 cases of antiviral induced DRESS are reported. European registry on severe cutaneous adverse drug reactions (RegiSCAR) was the usual used clinical diagnostic criteria. Most of the reports were related to, telaprevir. Rash and fever actually occurred in a large number of these patients. Eosinophilia was the most reported hematologic involvement. Liver injury is the most defined type of organ damage. Most of the patients managed with systemic corticosteroids. The death occurred in 1 patient from liver decompensation. The reactivation various viruses especially HHV-6 is reported in 2 Cases. The latency period was between 10 and 330 days after drug administration. It is necessary to perform more studies, especially those focused on the association between DRESS syndrome and viral reactivation and also its effective management.