Evaluating the Effects of Agomelatine on Polysomnography Parameters in Patients with Obstructive Sleep Apnea.

PURPOSE: Obstructive sleep apnea (OSA) is a common serious sleep disorder. Melatonin-based drugs such as agomelatine may have beneficial effects on patients with sleep disorders. This study aimed to evaluate agomelatine effects on polysomnography parameters in patients with OSA. METHODS: In this randomized, parallel, and single-blind study, seventy patients 18 years of age or older with obstructive sleep apnea who were referred to the sleep clinic were evaluated. The patients were randomly assigned into agomelatine and control groups. Patients in the agomelatine group received 50 mg agomelatine, one hour before sleep, for three consecutive nights prior to the polysomnography test, while the patients in the control group did not receive agomelatine. Sleep test parameters were compared between the two groups. RESULTS: Three parameters in the agomelatine versus control group showed significant differences. They were the median and interquartile range of the total sleep time, 397 [326.5-437.4] vs. 287.5 [184-393.1; p, 0.004] minuets, sleep efficiency percentage, 75.6 [71-87.4] vs. 65.1 [50.8-80.1; p, 0.005] and the wakening percentage, 7.5 [12.01-27.6] vs. 8.8[18.3-49; p, 0.004] agomelatine vs. control group. Other polysomnography parameters revealed no significant differences between the two groups. CONCLUSIONS: Agomelatine administration in patients with OSA may improve total sleep time, sleep efficiency percentage and the percentage of patients' awakening.

Effect of bromhexine in hospitalized patients with COVID-19.

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.

Evaluating the efficacy and safety of rivaroxaban as a warfarin alternative in chronic thromboembolic pulmonary hypertension patients undergoing pulmonary endarterectomy: A randomized clinical trial.

BACKGROUND AND AIM: Chronic thromboembolic pulmonary hypertension (CTEPH) is caused by the obstruction of the main pulmonary artery due to thrombosis and vascular remodeling. Regarding the need for anticoagulant therapy in CTEPH patients, this study aimed to compare rivaroxaban with warfarin in terms of its efficacy and safety in patients undergoing endarterectomy surgery. METHODS: The study was a parallel clinical trial in patients who underwent endarterectomy following CTEPH. A total of 96 patients were randomly selected and assigned to two groups: warfarin-treated (control) and rivaroxaban-treated (intervention). Patients were clinically assessed for re-thrombosis, re-admission, bleeding, and mortality in the first, third, and sixth months after surgery. RESULTS: There was no significant difference in the occurrence of thrombosis between the two groups within the first, third-, and sixth-months post-surgery (p=0.52, 1, 0.38 respectively). Moreover, the mortality rate (p=0.9), bleeding rate (p=0.06), and re-admission rate (p=0.15) showed no significant differences between the two groups. CONCLUSION: Rivaroxaban may be as effective as warfarin in treating CTEPH patients after endarterectomy in the short term and can be used as an anticoagulant in these patients. However, studies with long-term follow-ups are needed to consolidate the strategy of treating these patients with rivaroxaban.

Hemoptysis Resolution with Rituximab in Behçet's Disease: A Case Report.

Behçet's disease (BD) is a multisystem, progressive, and inflammatory disorder of unknown etiology. Vasculitis is believed to underlie various clinical manifestations of BD and is known to be one of the main causes of death due to BD, in cases of large vessel involvement. The current study is done in order to examine the effects of rituximab on the patient's debilitating clinical manifestations, as a result of not responding to the standard treatment regimens. The present case is a 28-year-old female patient with BD associated vasculitis. She was referred to the respiratory referral center, chiefly complaining of intermittent episodes of massive hemoptysis. She had also recurrent oral and genital ulcers, and difficulty in walking, despite considering the common treatment approaches for BD. Our patient received two courses of rituximab in combination with intravenous methylprednisolone. Over six months follow-up period from the date of treatment initiation with rituximab, symptoms of BD such as recurrent hemoptysis and aphthous ulcers were reduced in both frequency and severity. Lower limb weakness and difficulty in walking were improved as well. To summarize, rituximab appears to be an effective alternative for treatment-resistant vasculitis in BD patients.

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

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 H1N1 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.

Favipiravir Effects on the Control of Clinical Symptoms of Hospitalized COVID-19 Cases: An Experience with Iranian Formulated Dosage Form.

Coronavirus disease -19 (COVID-19) pandemic, caused by SARS-CoV-2, has gradually spread worldwide, becoming a major public health event. This situation requires designing a novel antiviral agent against the SARS-CoV-2; however, this is time-consuming and the use of repurposed medicines may be promising. One such medicine is favipiravir, primarily introduced as an anti-influenza agent in east world. The aim of this study was to evaluate the efficacy and safety of favipiravir in comparison with lopinavir-ritonavir in SARS-CoV-2 infection. In this randomized clinical trial, 62 patients were recruited. These patients had bilateral pulmonary infiltration with peripheral oxygen saturation lower than 93%. The median time from symptoms onset to intervention initiation was seven days. Favipiravir was not available in the Iranian pharmaceutical market, and it was decided to formulate it at the research laboratory of School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. The patients received favipiravir tablet at a dose of 1600 mg orally twice a day for day one and then 600 mg orally twice a day for days 2 to 6. In the second group, the patients received lopinavir-ritonavir combination tablet at a dose of 200/50 mg twice a day for seven days. Fever, cough, and dyspnea were improved significantly in favipiravir group in comparison with lopinavir-ritonavir group on days four and five. Mortality rate and ICU stay in both groups were similar, and there was no significant difference in this regard (P = 0.463 and P = 0.286, respectively). Chest X-ray improvement also was not significantly different between the two groups. Adverse drug reactions occurred in both groups, and impaired liver enzymes were the most frequent adverse effect. In conclusion, early administration of oral favipiravir may reduce the duration of clinical signs and symptoms in patients with COVID-19 and hospitalization period. The mortality rate also should be investigated in future clinical trials.

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

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; p = 0.00040). Our educational intervention had a positive impact on patients' knowledge regarding anticoagulation (p < 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.

Medication Interaction and Physicians' Compliance Assessment through Medication Reconciliation Forms in a University Affiliated Hospital.

Medication interactions are associated with various unwanted adverse drug reactions. Medication Reconciliation involves a process in which a complete list of patient's previously prescribed medications are recorded and subsequently evaluated within the context of concomitantly prescribed medications and present medical condition during the hospitalization. Medical records of randomly selected 270 patients hospitalized in internal medicine, cardiovascular and infectious diseases wards were evaluated. Drug interactions were checked by LexiComp® database. Each interaction was assigned a risk rating of A, B, C, D, or X. The progression from A to X was based on increased urgency for responding to the data. Completed reconciliation forms were attached to patient charts for evaluation of physicians' compliance. Drug interactions were observed in 65.2% (176/270) of cases. The risk rating of interactions was categorized as C, D and X in 54.2%, 32.4%, and 13.4% of cases, respectively. There was a positive correlation between the number of prescribed medications and the rate of interactions (p-value < 0.001, Kendall's correlation coefficient = 0.487). Moreover, the length of hospitalization and the rate of drug interactions were significantly correlated (p-value < 0.001, Kendall's correlation coefficient = 0.350). Cardiovascular agents constituted the largest proportion of interactions (25%) followed by antibiotics (18%) and immunosuppressive agents (6%). In 59.6% of cases, no corrective action was taken by the physicians. Medication discrepancies occur commonly in hospital settings. Structured medication reconciliation may have a positive impact on prevention of medication errors.

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

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% (p < 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.

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

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.