Publications by authors named "Farzaneh Dastan"

35 Publications

Efficacy and safety of Tocilizumab in severe and critical COVID-19: A Systematic Review and Meta-Analysis.

Expert Rev Clin Immunol 2021 Apr 7:1-13. Epub 2021 Apr 7.

Department of Clinical Pharmacy, Faculty of Medicine, Aja University of Medical Sciences, Tehran, Iran.

Objectives: Currently published papers and clinical guidelines regarding the effects of tocilizumab in severe and critical COVID-19 are contradictory. The aim of this meta-analysis was to combine the results of clinical studies of different designs to investigate the efficacy and safety of tocilizumab in severely-to-critically ill COVID-19 patients.

Methods: A systematic search was performed in PubMed, Embase, CENTRAL, ClinicalTrials.gov, Scopus, and preprint servers up to 26 December 2020. Since a substantial heterogeneity was expected, a random-effects model was applied to calculate the pooled effect size (ES) and 95% confidence interval (CI) for each study outcome.

Results: Forty-five comparative studies involving 13,189 patients and 28 single-arm studies involving 1,770 patients were analyzed. The risk of mortality (RR of 0.76 [95%CI 0.65 to 0.89], P < 0.01) and intubation (RR of 0.48 [95%CI 0.24 to 0.97], P = 0.04) were lower in tocilizumab patients compared with controls. We did not find any significant difference in secondary infections, length of hospital stay, hospital discharge before day 14, and ICU admission between groups.

Conclusion: Tocilizumab can improve clinical outcomes and reduce mortality rates in severe to critical COVID-19 patients. Large-scale randomized controlled trials are still required to improve the statistical power of meta-analysis.
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http://dx.doi.org/10.1080/1744666X.2021.1908128DOI Listing
April 2021

Effect of bromhexine in hospitalized patients with COVID-19.

J Investig Med 2021 Mar 15. Epub 2021 Mar 15.

Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Background: Bromhexine is a potent inhibitor of transmembrane serine protease 2 and appears to have an antiviral effect in controlling influenza and parainfluenza infection; however, its efficacy in COVID-19 is controversial.

Methods: A group of hospitalized patients with confirmed COVID-19 pneumonia were randomized using 1:1 allocation to either standard treatment lopinavir/ritonavir and interferon beta-1a or bromhexine 8 mg four times a day in addition to standard therapy. The primary outcome was clinical improvement within 28 days, and the secondary outcome measures were time to hospital discharge, all-cause mortality, duration of mechanical ventilation, the temporal trend in 2019-nCoV reverse transcription-polymerase chain reaction positivity and the frequency of adverse drug events within 28 days from the start of medication.

Results: A total of 111 patients were enrolled in this randomized clinical trial and data from 100 patients (48 patients in the treatment arm and 52 patients in the control arm) were analyzed. There was no significant difference in the primary outcome of this study, which was clinical improvement. There was no significant difference in the average time to hospital discharge between the two arms. There were also no differences observed in the mean intensive care unit stay, frequency of intermittent mandatory ventilation, duration of supplemental oxygenation or risk of death by day 28 noted between the two arms.

Conclusion: Bromhexine is not an effective treatment for hospitalized patients with COVID-19. The potential prevention benefits of bromhexine in asymptomatic postexposure or with mild infection managed in the community remain to be determined.
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http://dx.doi.org/10.1136/jim-2020-001747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970656PMC
March 2021

Approaches for the Treatment of SARS-CoV-2 Infection: A Pharmacologic View and Literature Review.

Iran J Pharm Res 2020 ;19(3):258-281

Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

The emergence of a novel Coronavirus disease (COVID-19) inducing acute respiratory distress syndrome (ARDS) was identified in Hubei province of China in December 2019 and rapidly spread worldwide as pandemic and became a public health concern. COVID-19 disease is caused by a new virus known as SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), which has recently offered many challenges and efforts to identify effective drugs for its prevention and treatment. Currently, there is no proven effective approach and medication against this virus. Quickly expanding clinical trials and studies on Coronavirus disease 2019 increase our knowledge regarding SARS-CoV-2 virus and introduce several potential drugs targeting virus moiety or host cell elements. Overall, 3 stages were suggested for SARS-CoV-2 infection according to the disease severity, clinical manifestations, and treatment outcomes, including mild, moderate, and severe. This review aimed to classify and summarize several medications and potential therapies according to the disease 3 stages; however, it is worth noting that no medication and therapy has been effective so far.
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http://dx.doi.org/10.22037/ijpr.2020.113821.14506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757982PMC
January 2020

No clinical benefit of high dose corticosteroid administration in patients with COVID-19: A preliminary report of a randomized clinical trial.

Eur J Pharmacol 2021 Apr 16;897:173947. Epub 2021 Feb 16.

Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

The aim of this study was to evaluate the clinical effects of dexamethasone administration in patients with mild to moderate acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19). The study included 50 patients who were randomly assigned to the dexamethasone group or control group. Dexamethasone was administered at a dose of 20 mg/day from day 1-5 and then at 10 mg/day from day 6-10. The need for invasive mechanical ventilation, death rate, duration of clinical improvement, length of hospital stay, and radiological changes in the computed tomography scan were assessed. The results revealed that 92% and 96% of patients in the dexamethasone and control groups, respectively, required noninvasive ventilation (P = 0.500). Among them, 52% and 44% of patients in the dexamethasone and control groups, respectively, required invasive mechanical ventilation (P = 0.389). At the end of the study, 64% of patients in the dexamethasone group and 60% of patients in the control group died (P = 0.500); the remaining patients were discharged from the hospital during the 28-day follow-up period. The median length of hospital stay was 11 days in the dexamethasone group and 6 days in the control group (P = 0.036) and the median length of hospital stay was 7 days in the dexamethasone group and 3 days in the control group (P < 0.001). No significant differences were observed in the other outcomes. This study showed that corticosteroid administration had no clinical benefit in patients with COVID-19-induced mild to moderate ARDS.
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http://dx.doi.org/10.1016/j.ejphar.2021.173947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885705PMC
April 2021

Successful Management of COVID-19 With Adalimumab in a Post-Coronary Artery Bypass Graft Surgery Patient.

J Cardiothorac Vasc Anesth 2021 Jan 7. Epub 2021 Jan 7.

Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

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http://dx.doi.org/10.1053/j.jvca.2020.12.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833423PMC
January 2021

Combination therapy of IFNβ1 with lopinavir-ritonavir, increases oxygenation, survival and discharging of sever COVID-19 infected inpatients.

Int Immunopharmacol 2021 Mar 26;92:107329. Epub 2020 Dec 26.

Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Interferon Beta-1a (IFN-β1-a), an immunomodulatory mediator with antiviral effects, has shown in vivo and in vitro activities especially on coronavirus including SARS-CoV-2. COVID-19 defined as the disease caused by infection with SARS-CoV-2. The virus has been illustrated inhibits the production of IFN-β1-a from inflammatory cells. We conducted a retrospective study of all adult confirmed COVID-19 hospitalized patients who received combination of three doses of 12 million international units of IFN-β1-a and Lopinavir 400 mg and Ritonavir 100 mg every 12 h (case group) for 14 days besides standard care and age- and sex- matched COVID-19 patients with receiving lopinavir/ritonavir (control group) at Masih Daneshvari Hospital as a designated hospital for COVID-19 between Feb 19 and Apr 30, 2020. Multivariate analysis was done to determine the impact of IFN-β1-a on outcome and all-cause mortality. 152 cases in IFN-β1-a group and 304 cases as control group were included. IFN-β1-a group stayed at hospital longer and required noninvasive ventilation more than control group (13 vs. 6 days, p = 0.001) and (34% vs. 24%, p = 0.04), respectively. During treatment, 57 (12.5%) patients died. The death rate in case and control groups was 11% and 13% respectively. In multivariate analysis, not receiving IFN-β1-a (HR 5.12, 95% CI: 2.77-9.45), comorbidity (HR 2.28, 95% CI: 1.13-4.60) and noninvasive ventilation (HR 2.77, 95% CI: 1.56-4.93) remained significantly associated with all-cause mortality. In this study, risk of death decreased by using IFN-β1-a in COVID-19 patients. More clinical study will be necessary to measure efficacy of IFN-β1-a in COVID-19 treatment.
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http://dx.doi.org/10.1016/j.intimp.2020.107329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762801PMC
March 2021

Can L-Carnitine Supplementation Improve Cardiopulmonary Function? A Randomized Controlled Clinical Trial in Hemodialysis Patients.

Iran J Kidney Dis 2020 Dec;14(6):494-499

Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti Medical University, Tehran, Iran.

Introduction: L-Carnitine is a cardioprotective agent which balances metabolism by promoting mitochondrial β-oxidation and facilitating transportation of long chain fatty acids into the mitochondrial matrix. It has been shown that L-Carnitine level in plasma and tissue is lower in hemodialysis patients and they may lose the benefits of this substance. The aim of this trial was to evaluate the effects of L-Carnitine supplementation on cardiorespiratory Function in hemodialysis patients through ergospirometry.

Methods: The current study was conducted on 46 chronic hemodialysis patients. The patients were divided into two groups. In both groups ergospirometry parameters (VE Max, VO2-Max and VCO2 Max, AT, VE/VCO2 Slope) were recorded for a 3-month period of time. During this period, one group received L-Carnitine at doses of 2 g/d orally and the other group received only placebo. After three months, all of the mentioned parameters reevaluated and statistical analysis was done.

Results: Only CRP value was different between two group and in placebo group increased significantly after 3 months (P < .05). No significant difference was detected in Cardio-respiratory factors. In terms of ergospirometry, PET-CO2 was the only parameter which was significantly increased in the treatment group but decreased in placebo group (P < .05).

Conclusion: Significant differences between our groups showed that L-Carnitine could help hemodialysis patients with cardiopulmonary problems to suffer lower rate of inflammation and poor life quality as shown at least in comparison of the two factors including CRP and PETCO2 at rest.
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December 2020

Clinical Manifestations of Patients with Coronavirus Disease 2019 (COVID-19) in a Referral Center in Iran.

Tanaffos 2020 Nov;19(2):122-128

Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Following the recent epidemic of coronavirus disease 2019 (COVID-19) in Wuhan, China, a novel betacoronavirus was isolated from two patients in Iran on February 19, 2020. In this study, we aimed to determine the clinical manifestations and outcomes of the first confirmed cases of COVID-19 infection (n=127).

Materials And Methods: This prospective study was conducted on all COVID-19-suspected cases, admitted to Masih Daneshvari Hospital (a designated hospital for COVID-19), Tehran, Iran, since February 19, 2020. All patients were tested for COVID-19, using reverse transcription-polymerase chain reaction (RT-PCR) assay. Data of confirmed cases, including demographic characteristics, clinical features, and outcomes, were collected and compared between three groups of patients, requiring different types of admission (requiring ICU admission, admission to the general ward, and transfer to ICU).

Results: Of 412 suspected cases, with the mean age of 54.1 years (SD=13.4), 127 (31%) were positive for COVID-19. Following the patients' first visit to the clinic, 115 cases were admitted to the general ward, while ten patients required ICU admission. Due to clinical deterioration in the condition of 25 patients (out of 115 patients), ICU admission was essential. Based on the results, the baseline characteristics of the groups were similar. Patients requiring ICU admission were more likely to have multiorgan involvement (liver involvement, P<0.001; renal involvement, P<0.001; and cardiac involvement, P=0.02), low O saturation (P<0.001), and lymphopenia (P=0.05). During hospital admission, 21 (16.5%) patients died, while the rest (83.5%) were discharged and followed-up until March 26, 2020. Also, the survival rate of patients, who received immunoglobulin, was higher than other patients (60.87% vs. 39.13%).

Conclusion: The mortality rate of COVID-19 patients was considerable in our study. Based on the present results, this infection can cause multiorgan damage. Therefore, intensive monitoring of these patients needs to be considered.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680520PMC
November 2020

Real Clinical Practice and Therapeutic Management Following COVID-19 Crisis in two Hospitals in Iran: A Statistical and Conceptual View.

Tanaffos 2020 Nov;19(2):112-121

Student Research Committee, Baqiyatallah University of Medical Sciences, Tehran, Iran.

Background: The Coronavirus disease 2019 (COVID-19) outbreak quickly has spread and became a pandemic. However, no approved therapeutics or effective treatment is available for the treatment of these patients. The present study was done to retrospectively assess the treatment strategies (e.g., pharmaceutical care services) for COVID-19 patients in selected hospitals and highlight the importance of such services in the management of a pandemic.

Materials And Methods: Data from a series of COVID-19 patients (978 patients; 658 males [66.9%] and 324 females [33.1%]) admitted to the selected hospitals in Tehran from 20 February to 19 March 2020 were retrieved retrospectively from the Health Information System (HIS) of the hospitals. The statistical tests were used for analyzing the effect and correlation of the variables (drugs) with the average length of stay (ALOS) in the hospital.

Results: Diverse medication classes and old drugs with or without strong evidence of therapeutic effects against the novel coronavirus, some previously tried as a treatment for SARS-CoV and MERS-CoV, were mostly used for the treatment of patients in the hospitals. Many medications (broad-spectrum antibiotics and antivirals) or combination therapies are used without evidence of their therapeutic effects during pandemics.

Conclusion: Therefore, guidelines should be provided for the off-label use of these drugs by policymakers and stakeholders during a pandemic emergency due to high demands. Also, monitoring of the HIS data can play an important role in improving public health response to emerging diseases.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680514PMC
November 2020

COVID-19 in Iran: A model for Crisis Management and Current Experience.

Iran J Pharm Res 2020 ;19(2):1-8

Department of Medical-Surgical Nursing, School of Nursing & Midwifery, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

In February 2020, the first sample test was confirmed as positive for corona virus in Masih Daneshvari Hospital that is the reference center in Iran for all pulmonary and respiratory diseases. The decisions made in a hospital or organization to manage a crisis is very vital. Success in managing any crisis requires a scientific and scholarly attitude. This paper was distilled from experiences gained in Masih Daneshvari Hospital in Tehran, capital of Iran, in March 2020 at the stubborn time of coping and managing corona virus crisis. This study was conducted using participatory action research, a methodology which identifies problems in practice, and finds methods to solve them. This Action research involves five stages: statement of the problem, planning, data interpretation and analysis, action, and evaluation of the research process during performing the study. The whole hospital was equipped for corona virus patients in 10 phases during one week and 250 active beds were equipped for these patients. Three models, namely, "corona virus crisis management model", "Pharmaceutical care management in coronavirus crisis model" and "nursing in coronavirus crisis model" were planned and implemented. During one month of implementing these three models, the supervision team monitored the accurate implementation of instructions and resolving or revising the possible deficiencies and faults. The Masih Daneshvari crisis management model in coronavirus, can be a useful and applicable model in other corona virus centers.
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http://dx.doi.org/10.22037/ijpr.2020.113365.14255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667532PMC
January 2020

Evaluating the effects of Intravenous Immunoglobulin (IVIg) on the management of severe COVID-19 cases: A randomized controlled trial.

Int Immunopharmacol 2021 Jan 13;90:107205. Epub 2020 Nov 13.

Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Background: The newly discovered coronavirus has turned into coronavirus disease 2019 (COVID-19) pandemic and it rages at an unprecedented rate. Considering the findings of previous studies on the use of Intravenous Immunoglobulin (IVIg) for treating severe HN infection and the satisfying results for reducing viral load and mortality, this study aimed to investigate the potential usefulness of IVIg for the management of severe cases.

Methods: In this randomized controlled trial, 84 patients were included: 52 in the IVIg group and 32 in the control group. The intervention group received IVIg at a dose of 400 mg/kg, IV, daily for three days. Both groups received hydroxychloroquine, lopinavir/ritonavir and supportive care. The demographic data, mortality rate, the need for mechanical ventilation, length of stay in hospital and in Intensive Care Unit (ICU), and imaging findings were recorded and compared in terms of the mentioned factors.

Results: The mean time from admission to IVIg initiation was 3.84 ± 3.35 days. There was no significant difference between the two groups in terms of mortality rate (P-value = 0.8) and the need for mechanical ventilation (P-value = 0.39). The length of hospital stay was significantly lower for the control group than that of the intervention group (P-value = 0.003). There was a significant positive relationship between the time from hospital admission to IVIg initiation and the length of stay in the hospital and ICU among the survivors (P-value < 0.001 and =0.01, respectively).

Conclusions: Our findings did not support the use of IVIg in combination with hydroxychloroquine and lopinavir/ritonavir in treatment of severe COVID-19 cases.
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http://dx.doi.org/10.1016/j.intimp.2020.107205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665876PMC
January 2021

Efficacy and safety of propolis mouthwash in management of radiotherapy induced oral mucositis; A randomized, double blind clinical trial.

Rep Pract Oncol Radiother 2020 Nov-Dec;25(6):969-973. Epub 2020 Oct 3.

Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Aim And Background: Propolis has been used for the management of oral mucositis in a number of studies. Due to lack of sufficient evidence especially in radiotherapy induced oral mucositis, the present study was designed to evaluate the efficacy and safety of propolis mouthwash in oral mucositis and dysphagia in patients undergoing head and neck radiotherapy.

Materials And Methods: This study was a prospective, randomised, double-blind, placebo-controlled trial. The patients randomly divided into two groups receiving either the propolis or the placebo mouthwash. Patients were advised to rinse their mouth with 15 mL three times daily for four weeks. Severity of mucositis and dysphagia were evaluated by the National Cancer Institute Common Toxicity Criteria (NCI-CTC) and Common Terminology Criteria for Adverse Events (CTCAE), respectively.

Results: Thirty patients completed the study. Each group consisted of 15 patients. Although, there is not any significant difference between two groups in the first week of radiotherapy, a significant difference was seen in the second, the third and the fourth week (p = 0.03, 0.02, 0.02, respectively). Dysphagia reported as a mild score in the propolis group only in the fourth week which is significant compared with the placebo group (p = 0.01). There is not any serious adverse effect related to propolis or placebo during the study.

Conclusion: It seems that propolis mouthwash is an effective and safe medication for alleviation of oral mucositis and dysphagia in patients under head and neck radiotherapy.
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http://dx.doi.org/10.1016/j.rpor.2020.09.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573287PMC
October 2020

Subcutaneous tocilizumab in adults with severe and critical COVID-19: A prospective open-label uncontrolled multicenter trial.

Int Immunopharmacol 2020 Dec 13;89(Pt B):107102. Epub 2020 Oct 13.

Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Potential therapeutic approaches in coronavirus disease 2019 (COVID-19) comprise antiviral and immunomodulatory agents; however, no immunomodulator drug has been approved. This multicenter, prospective, open-label, uncontrolled study aimed to assess the use of subcutaneous tocilizumab in adult patients with severe and critical COVID-19. Tocilizumab was added to the standard care of therapy at a dose of 324 mg (<100 kg bodyweight) or 486 mg (≥100 kg bodyweight). The study endpoints were all-cause mortality rate, changes in oxygen-support level, oxygen saturation, body temperature, respiratory rate, and laboratory variables during the study, and drug safety. Of 126 patients enrolled, 86 had severe and 40 had critical disease. Most patients were male (63.49%) and aged below 65 (78.57%). By day 14 of the study, 4.65% (4/86) of severe patients and 50.00% (20/40) of critical patients died. By the end, 6.98% (6/86) of severe patients and 60.00% (24/40) of critical patients died.Outcomes concerning three additional endpoints (oral temperature, oxygen saturation, and respiratory rate)were significantly improved as early as three days after tocilizumab administration in both groups of subjects, more considerably in severe patients. Significant improvement in the required level of oxygenation was reported in severe patients seven days after tocilizumab administration. No tocilizumab-related serious adverse event occurred in this study. Subcutaneous tocilizumab might improve some clinical parameters and reduce the risk of death in COVID-19 patients, particularly if used in the early stages of respiratory failure.
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http://dx.doi.org/10.1016/j.intimp.2020.107102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553010PMC
December 2020

A Fourteen-day Experience with Coronavirus Disease 2019 (COVID-19) Induced Acute Respiratory Distress Syndrome (ARDS): An Iranian Treatment Protocol.

Iran J Pharm Res 2020 ;19(1):31-36

Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.

COVID-19 is currently causing concern in the medical community as the virus is spreading around the world. It has a heavy global burden, particularly in low-income countries. The clinical spectrum of COVID-19 pneumonia ranges from mild to critically ill cases and Acute Respiratory Distress Syndrome. An expert panel was held and an internal protocol was developed to manage the COVID-19 induced ARDS according to WHO recommendations and NIH guidelines. Different therapeutic regimens were employed on this protocol based on the ARDS severity and the patients' special characteristics. The mortality rate, the rate of survivors, and non-survivors were reported. Of the 231 suspected cases of COVID-19 admitted to the hospital during two weeks, 72 patients were admitted to ICU with diagnosis confirmed by RT-PCR. In total, mortality in the ICU was 25% (n = 18) among ARDS patients over two weeks. COVID-19 induced ARDS is a major concern. The rapid progression of ARDS needs specific protocol based on patients' characteristics and rapid action.
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http://dx.doi.org/10.22037/ijpr.2020.113337.14239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462513PMC
January 2020

Thalidomide against Coronavirus Disease 2019 (COVID-19): A Medicine with a Thousand Faces.

Iran J Pharm Res 2020 ;19(1):1-2

Student Research Committee, Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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http://dx.doi.org/10.22037/ijpr.2020.113369.14259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462477PMC
January 2020

Promising effects of tocilizumab in COVID-19: A non-controlled, prospective clinical trial.

Int Immunopharmacol 2020 Nov 4;88:106869. Epub 2020 Aug 4.

Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Background: The clinical presentation of SARS-CoV-2 infection ranges from mild symptoms to severe complications, including acute respiratory distress syndrome. In this syndrome, inflammatory cytokines are released after activation of the inflammatory cascade, with the predominant role of interleukin (IL)-6. The aim of this study was to evaluate the effects of tocilizumab, as an IL-6 antagonist, in patients with severe or critical SARS-CoV-2 infection.

Methods: In this prospective clinical trial, 76 patients with severe or critical SARS-CoV-2 infection were evaluated for eligibility, and ultimately, 42 patients were included. Tocilizumab was administered at a dose of 400 mg as a single dose via intravenous infusion. Primary outcomes included changes in oxygenation support, need for invasive mechanical ventilation, and death. Secondary outcomes included radiological changes in the lungs, IL-6 plasma levels, C-reactive protein levels, and adverse drug reactions. The data were analyzed using SPSS software.

Results: Of the 42 included patients, 20 (48%) patients presented the severe infection stage and 22 (52%) were in the critical stage. The median age of patients was 56 years, and the median IL-6 level was 28.55 pg/mL. After tocilizumab administration, only 6 patients (14%) required invasive ventilation. Additionally, 35 patients (83.33%) showed clinical improvement. By day 28, a total of 7 patients died (6 patients in the critical stage and 1 patient in the severe stage). Neurological adverse effects were observed in 3 patients.

Conclusions: Based on the current results, tocilizumab may be a promising agent for patients with severe or critical SARS-CoV-2 infection, if promptly initiated during the severe stage.
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http://dx.doi.org/10.1016/j.intimp.2020.106869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402206PMC
November 2020

Assessment of Outpatients' Knowledge and Adherence on Warfarin: The Impact of a Simple Educational Pamphlet.

Iran J Pharm Res 2019 ;18(Suppl1):315-320

Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Warfarin is a critical medication that is broadly used for the treatment and prevention of thromboembolic disorders. Due to warfarin's narrow therapeutic index, it is crucial that patients follow an appropriate dosage regimen. Patient knowledge is one of the most important factors to safe and effective use of warfarin. Due to the obvious risks of anticoagulants administration, evaluating patients' awareness seems to be crucial. The purpose of this article was to evaluate the effects of intervention by an informative pamphlet on knowledge and adherence of patients who consumed warfarin. Two-hundred and fifty patients receiving warfarin were assigned to the study. They were asked to fill in the questionnaire. Then patients were provided with an educational pamphlet. In the second interview, patients filled the questionnaire again. Obtained data were assessed and analyzed by Excel software and SPSS version 18.0. Out of 250 patients who entered the study, 150 patients attended for the second interview. Data analysis revealed that out of 13 explanatory factors, only patients' literacy level and income were the predictors which inversely correlated with the patients' adherence (r = -0.44; = 0.00040). Our educational intervention had a positive impact on patients' knowledge regarding anticoagulation ( < 0.0001). Our findings revealed that a written informative pamphlet could effectively increase patients' anticoagulation knowledge. Since, poorly literate patients had a lesser level of knowledge before and after educational intervention, it is recommended to develop appropriate educational programs especially designed for this group of patients.
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http://dx.doi.org/10.22037/ijpr.2020.14766.12641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393044PMC
January 2019

The Potential Effect of Intravenous Calcitriol on the Ischemia-Reperfusion Process and Inflammatory Biomarkers in Patients Following Percutaneous Coronary Intervention (PCI).

Iran J Pharm Res 2019 ;18(Suppl1):282-290

Clinical Pharmacy Department, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

This study aimed to investigate the efficacy of calcitriol on Ischemia-reperfusion Injury (IRI) and inflammatory biomarkers in patients with non-ST-segment elevation acute coronary syndromes (NSTEACS) undergoing elective Percutaneous Coronary Intervention (PCI). A total of 72 patients with NSTEACS were randomly divided into two groups: (1) the calcitriol-treated group, treated with three mcg intravenous calcitriol administered before PCI (n = 36) and (2) the control-treated group (n = 36) The serum high-sensitivity C-reactive protein (hs-CRP), high-sensitivity interleukin-6 (hs-IL-6), creatinine kinase (CK)-MB and cardiac troponin I (cTnI) levels were measured before PCI and 24 h after PCI in both groups. The patients were followed up for the detection of the prevalence of major adverse cardiac events (MACE) in 180 days after PCI in both groups. Compared to pre-PCI, the serum hs-CRP, hs-IL-6, CK-MB, and cTnI levels were increased at 24 h after PCI (all < 0.05) in both groups. However, change in the levels of hs-CRP and hs-IL-6 were significant ( = 0.04 and = 0.02, respectively). Changes in the levels of CK-MB and cTnI were non-significant ( = 0.15 and = 0.39, respectively). No MACE (death, Q wave MI, target vessel revascularization, ischemic stroke) was detected in any patient in any group during a 3-month follow-up. Administration of calcitriol in patients with non-ST-segment elevation acute coronary syndromes undergoing elective PCI can attenuate the increase in serum inflammatory biomarkers in the serum (hs-CRP and hs-IL-6) and thus decrease the inflammatory reaction caused by PCI.
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http://dx.doi.org/10.22037/ijpr.2019.112469.13778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393057PMC
January 2019

The effects of melatonin on the oxidative stress and duration of atrial fibrillation after coronary artery bypass graft surgery: A Randomized Controlled Trial.

Endocr Metab Immune Disord Drug Targets 2020 Jul 28. Epub 2020 Jul 28.

Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran. 0.

Background: Atrial Fibrillation (AF) is a common complication following Coronary artery bypass graft (CABG) Surgery, which may be due to oxidative stress, necrosis and inflammation during CABG and can lead to increases the length of hospital stay and the risk of morbidity and mortality. Melatonin is a hormone with anti-oxidant and anti-inflammatory properties in the cardiovascular system. This study assessed the efficacy of sublingual consumption of melatonin in reducing necrosis and inflammation, in patients undergoing CABG with respect to C-reactive protein (hs-CRP), Creatine KinaseMuscle-Brain subunits (CK-MB) and cardiac Troponin T (cTnT) levels.

Methods: One hundred and two patients were enrolled and twenty-six patients were excluded during the study process and finally seventy-six patients undergoing CABG surgery randomly assigned to melatonin group (n = 38, 12 mg sublingual melatonin the evening before and 1 hour before surgery, or the control group which did not receive Melatonin, n = 38). Three patients in the melatonin group and three patients in the control group were excluded from the study because of discontinued intervention and lost to follow up. The samples were collected before and 24 hours after surgery. hs-CRP, CKMB, and cTnT levels were measured in all patients with the Elisa method.

Results: There was no significant difference in influencing variables among the groups at the baseline. The incidence of AF following CABG surgery was not statistically significant between the two groups, (p value = 0.71). However, the duration of AF (p value = 0.01), the levels of hs-CRP (p value = 0.001) and CK-MB (p value = 0.004) measured, 24 hours after surgery were significantly lower in the melatonin group. cTnT levels measured 24 hours post-CABG did not show any significant difference in both groups (p value = 0.52).

Conclusion: Our findings suggest that the administration of melatonin may help modulate oxidative stress, based on the reduction of the levels of hs-CRP, CK-MB, and the duration of AF following CABG surgery.
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http://dx.doi.org/10.2174/1871530320666200728152307DOI Listing
July 2020

Extracorporeal membrane oxygenation and COVID-19: The causes of failure.

J Card Surg 2020 Oct 17;35(10):2838-2843. Epub 2020 Jul 17.

Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Introduction: Venovenous extracorporeal membrane oxygenation (VV-ECMO) is a therapeutic strategy for the coronavirus disease 2019 (COVID-19) induced acute respiratory distress syndrome (ARDS). There are inconclusive data in this regard and causes of VV-ECMO failure are not yet understood well.

Case Series: Here, seven patients with COVID-19-induced ARDS who underwent VV-ECMO introduced and causes of VV-ECMO failure discussed. Medical records of seven COVID-19 patients treated with VV-ECMO were retrospectively evaluated to determine the clinical outcomes of VV-ECMO. Oxygenator failure occurred in four patients whom needed to oxygenator replacement. Successful VV-ECMO decannulation was done in three patients, however finally one patient survived.

Conclusions: Hypercoagulability state and oxygenator failure were the most main etiologies for VV-ECMO failure in our study. All patients with COVID-19 undergoing VV-ECMO should be monitored for such problems and highly specialized healthcare team should monitor the patients during VV-ECMO.
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http://dx.doi.org/10.1111/jocs.14867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404852PMC
October 2020

Subcutaneous administration of interferon beta-1a for COVID-19: A non-controlled prospective trial.

Int Immunopharmacol 2020 Aug 7;85:106688. Epub 2020 Jun 7.

Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Background: Recently, a new coronavirus spreads rapidly throughout the countries and resulted in a worldwide epidemic. Interferons have direct antiviral and immunomodulatory effects. Antiviral effects may include inhibition of viral replication, protein synthesis, virus maturation, or virus release from infected cells. Previous studies have shown that some coronaviruses are susceptible to interferons. The aim of this study was to evaluate the therapeutic effects of IFN-β-1a administration in COVID-19.

Methods: In this prospective non-controlled trial, 20 patients included. They received IFN-β-1a at a dose of 44 µg subcutaneously every other day up to 10 days. All patients received conventional therapy including Hydroxychloroquine, and lopinavir/ritonavir. Demographic data, clinical symptoms, virological clearance, and imaging findings recorded during the study.

Results: The mean age of the patients was 58.55 ± 13.43 years. Fever resolved in all patients during first seven days. Although other symptoms decreased gradually. Virological clearance results showed a significant decrease within 10 days. Imaging studies showed significant recovery after 14-day period in all patients. The mean time of hospitalization was 16.8 ± 3.4 days. There were no deaths or significant adverse drug reactions in the 14-day period.

Conclusions: Our findings support the use of IFN-β-1a in combination with hydroxychloroquine and lopinavir/ritonavir in the management of COVID-19.

Clinical Trial Registration Number: IRCT20151227025726N12.
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http://dx.doi.org/10.1016/j.intimp.2020.106688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275997PMC
August 2020

Sitagliptin Repositioning in SARS-CoV-2: Effects on ACE-2, CD-26, and Inflammatory Cytokine Storms in the Lung.

Iran J Allergy Asthma Immunol 2020 May 17;19(S1):10-12. Epub 2020 May 17.

Sarem Cell Research Center (SCRC), Sarem Women's Hospital, Tehran, Iran AND Department of Immunology, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

No Abstract.
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http://dx.doi.org/10.18502/ijaai.v19i(s1.r1).2849DOI Listing
May 2020

Tocilizumab administration in a refractory case of COVID-19.

Int J Antimicrob Agents 2020 Aug 2;56(2):106043. Epub 2020 Jun 2.

Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

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http://dx.doi.org/10.1016/j.ijantimicag.2020.106043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264941PMC
August 2020

Continues renal replacement therapy (CRRT) with disposable hemoperfusion cartridge: A promising option for severe COVID-19.

J Glob Antimicrob Resist 2020 06 27;21:340-341. Epub 2020 Apr 27.

Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Cytokine release syndrome is prevalent in severe cases of COVID-19. In this syndrome, an uncontrolled response of immune system occurs. Extracorporeal blood purification has been proven to effectively remove the released inflammatory cytokines. Here, we reported a successful case to represent our experience of extracorporeal blood purification in a patient with severe COVID-19.
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http://dx.doi.org/10.1016/j.jgar.2020.04.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185011PMC
June 2020

A comparative study of the analgesic effects of intravenous ketorolac, paracetamol, and morphine in patients undergoing video-assisted thoracoscopic surgery: A double-blind, active-controlled, randomized clinical trial.

Ann Card Anaesth 2020 Apr-Jun;23(2):177-182

Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Opioids are traditionally used as the drug of choice for the management of postoperative pain. However, their use is limited in patients undergoing Video-assisted thoracic surgery (VATS), due to their side effects, such as respiratory depression, nausea, and vomiting.

Aim: In this double-blind active-controlled randomized study, we have compared the analgesic effects of ketorolac and paracetamol to morphine.

Methods: Patients were randomly chosen from a pool of candidates who were undergoing VATS and were divided into three groups. During the first 24 h postsurgery, patients in the control group received a cumulative dose of morphine 20 mg, while patients in two treatment groups received ketorolac 120 mg and paracetamol 4 g in total. Doses were administered as bolus immediately after surgery and infusion during the first 24 h. Patients' pain severity was evaluated by visual analogue scale rating (VAS) at rest and during coughing episodes.

Results: The average pain score at recovery time was 2.29 ± 2.13 and 2.26 ± 2.16 for ketorolac and paracetamol, respectively, and it was significantly lower than the morphine group with an average pain score of 3.87 (P = 0.003). Additionally, the VAS score during cough episodes was significantly higher in the control group throughout the study period compared to study groups. Comparison of mean morphine dose utilized as liberation analgesic (in case of patients had VAS >3) between three groups was not significantly different (P = 0.17).

Conclusion: Our study demonstrates the non-inferiority of ketorolac and paracetamol to morphine in controlling post-VATS pain without causing any significant side effects. We also show that ketorolac and paracetamol are superior to morphine in controlling pain during 2 h postsurgery.
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http://dx.doi.org/10.4103/aca.ACA_239_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336963PMC
March 2021

Simultaneous Determination of Isoniazid, Pyrazinamide and Rifampin in Human Plasma by High-performance Liquid Chromatography and UV Detection.

Iran J Pharm Res 2019 ;18(4):1735-1741

Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Therapeutic Drug Monitoring (TDM) of first-line anti-tuberculosis (TB) drugs is a decisive tool, allowing the clinician to successfully treat TB patients. The objective of the study was to develop and optimize a simple, sensitive, and reliable high-performance liquid chromatography (HPLC) method for the simultaneous determination of isoniazid (INH), pyrazinamide (PZA), and rifampin (RIF) levels in human plasma. Nicotinamide was used as the internal standard and the samples were prepared after protein precipitation using acetonitrile and zinc sulfate. The separation was achieved using a C18 reversed-phase applying gradient elution. The mobile phase was a combination of water-methanol solution with a ratio of 95:05 (v/v) at the initial phase. All calibration curves had good linearity (r > 0.99) and the inter- and intra-day RSDs were lower than 15%. The limit of detection with a signal-to-noise ratio (S/N) of 3:1 was 0.16, 0.5, and 0.33 μg mL for INH, PZA, and RIF, respectively. The method presented here was selective, sensitive, and reproducible, and could be used for‌ therapeutic drug monitoring in the patients who were under treatment with these drugs.
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http://dx.doi.org/10.22037/ijpr.2019.1100849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059034PMC
January 2019

Effects of High-Dose Vitamin D Replacement on the Serum Levels of Systemic Inflammatory Biomarkers in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

COPD 2019 08 25;16(3-4):278-283. Epub 2019 Sep 25.

Chronic Respiratory Disease Research Center, National Research Institute of Tuberculosis and Lung Disease (NRITLD), Shahid Beheshti University of Medical Sciences , Tehran , Iran.

Chronic Obstructive Pulmonary Disease (COPD) is associated with increased inflammatory responses to noxious particles, which can be further enhanced during Acute Exacerbation of COPD (AECOPD). Considering the important immunoregulatory function of vitamin D, high prevalence of Vitamin D Deficiency (VDD) in COPD patients and a negative link between vitamin D levels and inflammatory biomarkers, suggests the seemingly interesting mechanism of vitamin D effects on inflammation resolution during the conventional treatment of AECOPD. The admitted AECOPD patients with VDD were recruited and randomly allocated to receive either 300,000 IU of intramuscular vitamin D ( = 35) or placebo ( = 35). Primary outcomes included inflammation resolution dynamics, which were assessed by monitoring the serum levels of IL-6, IL-8, and hs-CRP. Symptom recovery was evaluated based on the modified Medical Research Council (mMRC) dyspnea scale on the 1st and 6th days of admission. Secondary outcomes included the length of hospital stay (LOS) and 30-day mortality rates. Inflammatory biomarkers were highest at Day 1. Baseline vitamin D levels were 11.25 ± 3.09 and 10.59 ± 3.90 ng/ml ( = 0.45), which reached 11.35 ± 3.16 and 18.17 ± 4.24 by Day 6 ( < 0.001) in the placebo and, vitamin-D groups, respectively. IL-6 levels significantly decreased in the vitamin-D vs. placebo group on the 6 day ( = 0.02); however, no significant differences were observed in IL-8 ( = 0.15) and hs-CRP ( = 0.24) levels, mMRC scale ( = 0.45), LOS ( = 0.20), and mortality rates ( = 0.61). Vitamin D replacement as adjunctive therapy may accelerate inflammation resolution in hospitalized AECOPD patients. Further studies were needed to establish vitamin D exact role on inflammation resolution in AECOPD.
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http://dx.doi.org/10.1080/15412555.2019.1666812DOI Listing
August 2019

Study Protocol on Antimicrobial Stewardship in a Tertiary Respiratory Referral Hospital.

Tanaffos 2018 Mar;17(3):183-187

Clinical Tuberculosis and Epidemiology Research Center, NIRTLD, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Antimicrobial stewardship program is a comprehensive, longitudinal program designed to improve and measure the appropriateness of antimicrobial use while increasing patients' safety, decreasing cost of patients' care, and combating emerging antimicrobial resistance. Antimicrobial resistance, specially emerging multidrug-resistance and extremely drug-resistance gram negative bacteria, is an important concern in the modern world. This is particularly problematic since antimicrobials in production pipelines are not meeting the demand for the emerging resistance micro-organisms; in another word "we are running out of options". Indiscriminate use of antimicrobial may increase the risk for resistance, and drug toxicity. The aim of this study is to implement an evidence-based antimicrobial stewardship program in a tertiary referral hospital. This study will assure consistency of the stewardship program and measure outcomes to further assess the effectiveness of this program.

Materials And Methods: After establishment of antimicrobial stewardship committee and endorsement of policies the program will be conducted in all hospital medical wards. In an observational study, all patients receiving antimicrobials included in the program will be closely monitored for primary and secondary outcomes. Hospital's antimicrobial resistance patterns are monitored periodically to assess improvement. The quality indicators will be assessed to ensure proper execution of the program over time.

Results: As a study protocol, there are no results available to be reported at this time.

Conclusion: We are expecting to observe significant reduction in cost of antibiotic use shortly after program execution. By more appropriate utilization of antibiotics patients' safety will be increased. Furthermore, we are expecting to detect improvement in antimicrobial resistance patterns.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428375PMC
March 2018

Reducing Inappropriate Utilization of Albumin: The Value of Pharmacist-led Intervention Model.

Iran J Pharm Res 2018 ;17(3):1125-1129

Pharmacovigilance Department, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Albumin is known as a human blood product, with high cost and limited availability. Several studies have demonstrated the extent in which albumin is being utilized in controversial indications not supported or weakly supported by the available literature. To rationalize the use of albumin and to decrease the inappropriate cost of this expensive drug` a two phase study, with equal length of 66-days, comprising an observational drug utilization evaluation and a pharmacist-led audit and feedback interventional study, was conducted in a tertiary referral hospital in Tehran, Iran. The results of the interventional phase including the introduction of evidence-base guideline for albumin via a pharmacist-led audit and feedback intervention was compared to the ones from the observational phase. A total of 90 and 45 patients were included in the phase one and phase two of the study respectively. During the initial phase, 1870 albumin vials were used, of which 1467 (78.4%) vials were prescribed inappropriately. Inappropriate use of albumin was decreased significantly by 79.3% ( < 0.001) through the interventional phase, leading to 38,800 USD reduction in inappropriate costs of albumin. Introduction of evidence based guideline in conjugation with pharmacist-led audit and feedback can significantly decrease the inappropriate use of albumin. These results also demonstrate shifting towards a more evidence-based practice, which can increase patient's safety and enhance quality of care.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6094441PMC
January 2018