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   Table of Contents - Current issue
Coverpage
July-September 2017
Volume 6 | Issue 3
Page Nos. 135-191

Online since Thursday, September 21, 2017

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REVIEW ARTICLE  

Tumor necrosis factor-alpha antibodies in fistulizing crohn's disease: An updated systematic review and meta-analysis p. 135
Pardis Zaboli, Mohammad Abdollahi, Shilan Mozaffari, Shekoufeh Nikfar
DOI:10.4103/jrpp.JRPP_17_46  
Medical treatment for fistulizing Crohn's disease (FCD) is changing rapidly over the time by the introduction of novel therapeutic medicines, while no global consensus is available. This study aims to accomplish a systematic review and meta-analysis on the efficacy of tumor necrosis factor-alpha antibodies (anti-TNF-α antibodies) versus placebo in FCD. A systematic review of published literature was carried out till December 2016, and a meta-analysis of identified studies was done. Data have been explored from PubMed, Scopus, Cochrane Library Database, and Web of Science. Predefined exclusion criteria for included studies in meta-analysis are based on search methodology and are as follows: Randomized clinical trial about Crohn's disease (CD) patients without fistula, pediatrics CD, randomized clinical trials about pregnant women with FCD, nonhuman studies, randomized clinical trials with surgical therapies interventions, conference abstracts, case reports, and language other than English studies. All randomized placebo-controlled trials were included. To assess risk of bias, Jadad score was applied to evaluate trials' methodological quality. Relative risk (RR) and 95% confidence intervals were computed using Mantel-Haenszel and/or Rothman-Boice (for fixed effects) or Der Simonian-Laird (for random effects) techniques. Nine studies attained defined inclusion criteria. The meta-analysis results showed that anti-TNF-α antibodies are remarkably more effective in comparison to placebo for fistula closure maintenance (RR = 2.36; 95% confidence interval: 1.58–3.55; P < 0.0001) in patients with FCD, whereas anti-TNF-α antibodies were not superior to placebo neither in fistula improvement nor in fistula closure. We concluded that adalimumab and certolizumab pegol are both effective in fistula closure maintenance in adult patients with FCD.
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ORIGINAL ARTICLES Top

Missing the benefit of metformin in acute myeloid leukemia: A problem of contrast? p. 145
Alice C Ceacareanu, George K Nimako, Zachary A. P. Wintrob
DOI:10.4103/jrpp.JRPP_17_37  
Objective: To evaluate whether metformin's cancer-related benefits reported in patients with solid tumors (ST) are also present in acute myeloid leukemia (AML) patients. Methods: Baseline demographic and clinical history for all diabetes mellitus patients newly diagnosed with AML or cancer of the breast, ovary, prostate, gastrointestinal tract, lung, or kidney at Roswell Park Cancer Institute in Buffalo, NY (January 2003–December 2010, n = 924) was collected. Overall survival (OS) and disease-free survival (DFS) were assessed by Kaplan–Meier (KM) analysis and Cox proportional hazards regression (hazard ratio [HR]). Findings: Baseline metformin use provided significant OS and DFS benefit in ST but not in AML (KM: PST-OS= 0.003; PST-DFS= 0.002; PAML-OS= 0.961; PAML-DFS= 0.943). AML median survival was slightly better with metformin use, but users derived no relapse benefit. In ST, metformin nonusers had shorter median survival, 57.7 versus 86 months, and poorer outcomes (HRST-OS= 1.33; PST-OS= 0.002; HRST-DFS= 1.32; PST-DFS= 0.002). These findings remained significant in age-adjusted models (HRST-OS= 1.21; PST-OS= 0.039; HRST-DFS= 1.23; PST-DFS= 0.02) but not fully adjusted models (HRST-OS= 0.96; PST-OS= 0.688; HRST-DFS= 1.0; PST-DFS= 0.94). Higher mortality was noted in AML patients taking insulin versus oral diabetes pharmacotherapy at baseline (HRAML-OS= 2.03; PAML-OS= 0.04). Conclusion: Lack of metformin benefit in AML could be due to advanced age at cancer diagnosis. Metformin substitution with insulin before computed tomography scans with contrast – a frequent AML assessment practice – may also explain the lack of subsequent benefit despite taking metformin at baseline. A temporary metformin substitution is recommended by the package insert due to a possible drug interaction with the contrast dye. Our data suggest that metformin substitution was permanent in many patients. Nonetheless, the observed benefit in other malignancies warrants further investigation of metformin use in AML.
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Impact of CYP2C19 polymorphisms on serum concentration of voriconazole in iranian hematological patients p. 151
Sholeh Ebrahimpour, Soha Namazi, Mehdi Mohammadi, Mohsen Nikbakht, Molouk Hadjibabaie, Hamidreza Taghvaye Masoumi, Ardeshir Ghavamzadeh
DOI:10.4103/jrpp.JRPP_17_31  
Objective: This study aimed to determine the portion of Iranian patients who attain therapeutic serum concentrations of voriconazole (VRCZ) following administration of fixed doses. In addition, the effect of CYP2C19 polymorphism on serum levels of VRCZ was also investigated. Methods: Forty-eight adult patients of Iranian origin with hematologic malignancies, who received VRCZ for treatment of invasive aspergillosis, were recruited into the study. Blood samples were drawn at day 4 of treatment to measure trough drug concentrations and determine genotyping of CYP2C19 polymorphisms of each patient. High-performance liquid chromatography method was used for measuring VRCZ serum level and CYP2C19 polymorphisms were conducted by Sanger sequencing. Demographic and clinical characteristics of patients alongside with CYP2C19 polymorphisms were assessed to determine the effective factor/s on VRCZ serum concentration. Findings: Seventy-three percent of patients achieved therapeutic serum concentrations of VRCZ with administration of usual fixed doses in clinical practice. There was no correlation between weight-adjusted dose and serum concentrations of VRCZ. Mean serum levels were significantly different neither in genders nor in routes of administrations. Extensive and ultrarapid metabolizers (URMs) comprised 48.7% and 21.6% study population, respectively. CYP2C19 polymorphism dramatically influenced the trough levels of VRCZ, so that all patients with subtherapeutic levels expressed URM phenotype. Conclusion: With respect to high incidence of URM phenotype in Iranian population, and observed association of this phenotype with sub-therapeutic levels in our study, performing therapeutic drug monitoring is strongly recommended for all patients.
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Causes of medication errors in intensive care units from the perspective of healthcare professionals p. 158
Sedigheh Farzi, Alireza Irajpour, Mahmoud Saghaei, Hamid Ravaghi
DOI:10.4103/jrpp.JRPP_17_47  
Objective: This study was conducted to explore and to describe the causes of medication errors in Intensive Care Units (ICUs) from the perspective of physicians, nurses, and clinical pharmacists. Methods: The study was conducted using a descriptive qualitative method in 2016. We included 16 ICUs of seven educational hospitals affiliated to Isfahan University of Medical Sciences. Participants included 19 members of the healthcare team (physician, nurse, and clinical pharmacist) with at least 1 year of work experience in the ICUs. Participants were selected using purposeful sampling method. Data were collected through semi-structured individual interviews and were used for qualitative content analysis. Findings: The four main categories and ten subcategories were extracted from interviews. The four categories were as follows: “low attention of healthcare professionals to medication safety,” “lack of professional communication and collaboration,” “environmental determinants,” and “management determinants.” Conclusion: Incorrect prescribing of physicians, unsafe drug administration of nurses, the lack of pharmaceutical knowledge of the healthcare team, and the weak professional collaboration lead to medication errors. To improve patient safety in the ICUs, healthcare center managers need to promote interprofessional collaboration and participation of clinical pharmacists in the ICUs. Furthermore, interprofessional programs to prevent and reduce medication errors should be developed and implemented.
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Knowledge, attitude and practice of iranian pharmacists, body builders, and their coaches regarding sports supplements p. 166
Peivand Bastani, Ali Amjad Nia, Mohammadreza Shabanpoor, Safoora Mehravar, Sara Kashefian
DOI:10.4103/jrpp.JRPP_17_35  
Objective: This study is conducted on Iranian pharmacists, coaches, and athletes regarding sports supplements to assess their knowledge, attitude, and practice (KAP) regarding sports supplements. Methods: This was a cross-sectional study conducted in 2015. The study population consisted of all community pharmacists, bodybuilders, and bodybuilding coaches. The questionnaire was applied consisting some demographic questions and 25 questions for assessing KAP (6, 9, and 10, respectively). The collected data were analyzed with independent t-test, ANOVA, and Pearson correlation. Findings: In all three studied groups, the mean of KAP was upper than intermediate level 3 (P < 0.05) except the pharmacists' knowledge. A statistically significant difference appears between knowledge and age of pharmacists (P = 0.007). In addition, there was a significant relationship between coaches' practice and age (P = 0.04). Conclusion: According to the results although the studied groups have the intermediate level of KAP, organized and regular education courses are highly recommended along with paying more attention to the curriculum taught in the pharmacy schools according to the community current needs.
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BRIEF COMMUNICATIONS Top

Melatonin supplementation may improve the outcome of patients with hemorrhagic stroke in the intensive care unit p. 173
Mehrnoush Dianatkhah, Atabak Najafi, Mohammad Sharifzadeh, Arezoo Ahmadi, Hamidreza Sharifnia, Mojtaba Mojtahedzadeh, Farhad Najmeddin, Azadeh Moghaddas
DOI:10.4103/jrpp.JRPP_17_49  
Objective: Although mechanical ventilation is frequently a life-saving therapy, its use can result in unwanted side effects. It has been well documented that the choice of sedating agent may influence the duration of mechanical ventilation. Melatonin is a sedative and analgesic agent without any respiratory depressant effect which makes it an attractive adjuvant for sedation in the intubated patients. The aim of this study is to evaluate the effect of melatonin on the duration of mechanical ventilation in patients with hemorrhagic stroke. Methods: Forty adult intubated patients with hemorrhagic stroke, who were admitted to the Intensive Care Unit (ICU) within 24 h of onset, were enrolled in this randomized double-blind study. Subjects in the melatonin group received 30 mg of melatonin every night throughout the nasogastric tube. Length of ICU stay, mortality, and duration of mechanical ventilation were recorded for all patients. Findings: The duration of mechanical ventilation and length of ICU stay were shorter in patients who received melatonin in comparison with the control group, and this difference was statistically significant for the length of ICU stay and marginally significant for the duration of mechanical ventilation. Although not statistically significant, the mortality rate of the control group was 30%, almost double that of the study group (15%). Conclusion: Melatonin possesses hypnotic, analgesic, anti-inflammatory, and anti-oxidative properties that distinguish it as an attractive adjuvant in patients under mechanical ventilation. In conclusion, the administration of melatonin may facilitate the weaning process through decreasing the consumption of sedatives with respiratory depressant properties as well as preventing ventilator-associated lung injury.
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An interprofessional collaboration between medicine and pharmacy schools: Designing and evaluating a teaching program on practical prescribing p. 178
Mohammad Reza Javadi, Mina Khezrian, Anahita Sadeghi, Seyed Hossein Hajimiri, Kaveh Eslami
DOI:10.4103/jrpp.JRPP_17_16  
Objective: Medical students need proper education in drug prescription. The aim of the present study is to introduce a course that improves the students' prescribing skills and also promotes an interprofessional collaboration between medicine and pharmacy schools. Methods: This study was done in a skill laboratory at the pharmacotherapy department of Tehran University of Medical Sciences, Tehran, Iran. The course was an 18-h interactive workshop in 3 days under the supervision of clinical pharmacists. A total of 18 medical students participated in these classes before their internship. Before and after each class, they were given tests and paired t-test was done to compare the marks. Findings: A total of 18 medical students participated in this study. The results showed that the knowledge of the students on pharmacotherapy, drug information, and prescribing skills has been significantly improved at the end of the course. Conclusion: Using clinical pharmacists to the present pharmacotherapy course could be an effective model for medical students to obtain better prescribing skills.
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CASE REPORTS Top

Osteonecrosis of the jaws in patient received bisphosphonates and sunitinib separately: A case report p. 182
Farzaneh Ashrafi, Ali Derakhshandeh, Bijan Movahedian, Azadeh Moghaddas
DOI:10.4103/jrpp.JRPP_17_36  
Recently published reports have suggested that antiangiogenic drugs such as sunitinib could potentiate the osteonecrosis of the jaw (ONJ) induced by bisphosphonates (BPs) and even induce this adverse effect per se. We reported a case of ONJ with renal cell carcinoma under sunitinib medication and history of BPs therapy. A 53-year-old man was referred to the oral surgery clinic complaining of painful exposed oral lesion and bone extraction from right lower jaw in the mouth. He underwent nephrectomy followed by 5 months treatment with cycles of 50 mg sunitinib (Sutent®) once a day for 4 weeks followed by 2 weeks drug free before lesion exposure in October 2016. However, the patient has encounter to intermittent mucositis and gingivitis in oral cavity several times. Our patient had a history of zoledronic acid (4 mg intravenously two times) administration due to primary cancer misdiagnosis. In our case, no dental procedure contributed to the occurrence of ONJ. The lesion was improved by sunitinib cessation and administration of antibiotics through 2 weeks. Mucosal injury induction as well as inhibition of angiogenic signaling pathways by sunitinib administration may have precipitated the occurrence of ONJ. In addition, a possible synergistic effect by previously BP treatment is another accused.
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Intracranial hemorrhage in methanol toxicity: Challenging the probable heparin effect during hemodialysis p. 186
Hossein Hassanian-Moghaddam, Hooman Bahrami-Motlagh, Nasim Zamani, Seyed Amirhossein Fazeli, Behdad Behnam
DOI:10.4103/jrpp.JRPP_17_39  
Brain hemorrhages are rare complications of acute methanol poisoning. There is a debate on association of brain hemorrhage in methanol toxicity and application of systemic anticoagulation during hemodialysis (HD). A 70-year-old male presented to us with severe metabolic acidosis and a methanol level of 7.6 mg/dL. Ethanol and folinic acid were administered, and HD was performed. Brain computed tomography (CT) scan which was normal on presentation showed extensive bilateral subcortical supratentorial hypodensities on the 3rd day after commencing the treatment. However, the next CT scan performed 2 weeks later revealed expanding hemorrhagic transformation in previous hypodensities. Hemorrhagic changes could not be explained by patient's coagulation profile on the 3rd day. Anticoagulation agents such as heparin are used routinely during a dialysis session to prevent clot formation in dialysis circuits. This case is possibly questioning the role of heparin in hemorrhagic brain lesions of methanol intoxication.
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LETTER TO THE EDITOR Top

Intralesional bevacizumab (Avastin®) as a novel addition to infantile hemangioma management: A medical hypothesis p. 190
Mohsen Pourazizi, Sattar Kabiri, Bahareh Abtahi-Naeini
DOI:10.4103/jrpp.JRPP_17_38  
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