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Objective: Since the identification and spread of the novel coronavirus disease 2019 (COVID-19) in December 2019, respiratory presentations have been introduced as the main symptoms of this new type of viral disease; however, the extra-pulmonary features are raising awareness for researchers due to the vast diversity of vital organs affected by the virus. Among the wide range of clinical manifestations, limited data are available regarding rhabdomyolysis (RML) in COVID-19. Case Presentation: In this report, we present a 58-year-old woman with COVID-19 presenting with RML, with extremely elevated creatinine phosphokinase (CPK) and lactate dehydrogenase (LDH) levels (3283 and 1280 U/L, respectively) as the second sign of disease. Since the onset of the COVID-19 pandemic, several COVID-19 induced RML cases have been reported, and timely diagnosis and proper management are of paramount importance. Conclusion: Due to the findings that rhabdomyolysis can be a critical and missed cause of myalgia in COVID-19 patients, the importance of checking the serum level of CPK in patients with myalgia and fatigue in the era of COVID-19 upon their arrival will be highlighted.

Background: The pathophysiology of cardiac arrest (CA) involves over-activation of systemic inflammatory responses, relative adrenal insufficiency, and glycocalyx damage. Corticosteroids have beneficial effects in preventing the perturbation of the endothelial glycocalyx. Objectives: The aim of this systematic review was to determine the efficacy of glucocorticoids in patients with cardiac arrest. Methods: We searched PubMed, Scopus, ISI Web of Science, Google Scholar, and Cochrane central register for relevant clinical trials and cohort studies until September 2019. Results: We retrieved 7 peer-reviewed published studies for the systematic review. Two studies were clinical trials evaluating 147 patients, while five illustrated cohort design, evaluating 196,192 patients. In total, 196,339 patients were assessed. There was limited evidence and conflicting results to establish a correlation between glucocorticoids and the survival of patients suffering from cardiac arrest. However, the links between these medications and survival-to-admission, survival-to discharge, and 1-year survival rates were strong and consistent in observational studies. Conclusion: The clinical evidence regarding the efficacy and safety of glucocorticoids in CA is limited to observational studies with inconsistent methodology and few clinical trials with a small sample size. Nevertheless, it seems that glucocorticoid supplementation during and after cardiopulmonary resuscitation (CPR) may have beneficial effects in terms of survival-to-admission, survival to discharge, 1-year survival rates, and an improved return of spontaneous circulation (ROSC) rate, especially in patients with hemodynamic instability and cardiovascular diseases (i.e., refractory hemodynamic shock). Future studies with high-quality, large-scale, long-term intervention and precise baseline characteristics are needed to evaluate the exact effective dose, duration, and efficacy of glucocorticoids in CA.

Background We aimed to ascertain risk indicators of in‐hospital mortality and severity as well as to provide a comprehensive systematic review and meta‐analysis to investigate the prognostic significance of the prognostic nutrition index (PNI) as a predictor of adverse outcomes in hospitalized coronavirus disease 2019 (COVID‐19) patients. Methods In this cross‐sectional study, we studied patients with COVID‐19 who were referred to our hospital from February 16 to November 1, 2020. Patients with either a real‐time reverse‐transcriptase polymerase chain reaction test that was positive for COVID‐19 or high clinical suspicion based on the World Health Organization (WHO) interim guidance were enrolled. A parallel systematic review/meta‐analysis (in PubMed, Embase, and Web of Science) was performed. Results A total of 504 hospitalized COVID‐19 patients were included in this study, among which 101 (20.04%) patients died during hospitalization, and 372 (73.81%) patients were categorized as severe cases. At a multivariable level, lower PNI, higher lactate dehydrogenase (LDH), and higher D‐dimer levels were independent risk indicators of in‐hospital mortality. Additionally, patients with a history of diabetes, lower PNI, and higher LDH levels had a higher tendency to develop severe disease. The meta‐analysis indicated the PNI as an independent predictor of in‐hospital mortality (odds ratio [OR] = 0.80; P < .001) and disease severity (OR = 0.78; P = .009). Conclusion Our results emphasized the predictive value of the PNI in the prognosis of patients with COVID‐19, necessitating the implementation of a risk stratification index based on PNI values in hospitalized patients with COVID‐19.

Background The role of angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) has been addressed in some studies related to the current coronavirus disease-2019 (COVID-19) pandemic with possible higher severity and mortality in patients with hypertension. A triple-blind randomized controlled trial was designed to evaluate the effects of these medications on the COVID-19 progression. Methods Patients were enrolled in this trial between April and September 2020. They were randomized in two groups. The former dosage of ACEis/ARBs was continued in one group while in another group, the ACEis/ARBs were replaced by amlodipine ± carvedilol according to the dose equivalents. The primary outcomes were length of stay in hospitals and intensive care units. Other outcomes include mechanical ventilation, non-invasive ventilation, readmission, and COVID-19 symptoms after discharge. Results We randomized 64 patients with COVID-19 into two groups. Most patients were aged 66-80 and 46-65 years-old, 33 (51.6%) and 27 (42.2%), respectively. The study groups were nearly similar in baseline vital signs and characteristics. In addition, there was no significant difference in terms of recorded systolic and diastolic blood pressure measurements between groups. Furthermore, we did not find a significant difference between the days of intensive care unit or ward admission, the discharge rate, or readmission rates between the two groups. Conclusions This randomized triple-blind multi-centric clinical trial did not show any deleterious effects of ACEi/ARB medications in hypertensive COVID-19 patients., Graphical Abstract Graphical Abstract

Remdesivir (RDV) is the main antiviral for the treatment of moderate to severe forms of Coronavirus disease 2019 (COVID-19). Several studies revealed a shortening time to clinical improvement of COVID-19 and mortality benefits in patients receiving RDV. The patients with renal disease were excluded from large clinical trials of RDV, and the probable nephrotoxicity of the drug, its metabolites, and the vehicle (sulfobutylether-β-cyclodextrin) have led to the recommendation against using RDV in patients with an estimated glomerular filtration rate of30 mL/min.This systematic review aimed to collect data about the necessity and safety administration of RDV in the setting of renal impairment.Search through databases including MEDLINE, ScienceDirect, Cochrane Library, and PubMed was performed. The studies were carried out in adults and enrolled patients with different types of renal impairment (ie, acute kidney injury, chronic kidney disease, kidney transplant, and renal replacement therapy) were included. Eligible studies were assessed, and required data were extracted.Twenty-two cross-sectional studies, cohorts, case reports, and case series were included in this review. The mortality rate was between 7.3% and 50%, and various severity of COVID-19 was included in the studies. None of them reported an increase in adverse effects attributed to RDV administration. A decrease in inflammatory mediators and other benefits were obvious.Although the manufacturer's labeling does not recommend RDV administration in patients with severe renal impairment, it seems that nephrotoxicity is less concerning in the population of these patients. Moreover, RDV may be helpful in acute kidney injury induced by the viral invasion of COVID-19. To the best of our knowledge, this is the first systematic review of the use of RDV in kidney failure. Larger, well-designed, and pharmacokinetic studies are required to have a safe and logical recommendation about the use of RDV in patients with renal disorders.

Although rifampicin (RIF) is used as a synergistic agent for multidrug-resistant Acinetobacter baumannii (MDR-AB) infection, the optimal pharmacokinetic (PK) indices of this medication have not been studied in the intensive care unit (ICU) settings. This study aimed to evaluate the PK of high dose oral RIF following fasting versus fed conditions in terms of achieving the therapeutic goals in critically ill patients with MDR-AB infections.29 critically ill patients were included in this study. Under fasting and non-fasting conditions, RIF was given at 1200 mg once daily through a nasogastric tube. Blood samples were obtained at seven time points: exactly before administration of the drug, and at 1, 2, 4, 8, 12, and 24 h after RIF ingestion. To quantify RIF in serum samples, high-performance liquid chromatography (HPLC) was used. The MONOLIX Software and the Monte Carlo simulations were employed to estimate the PK parameters and describe the population PK model.The mean area under the curve over the last 24-h (AUCIn critically ill patients with MDR-AB infections, neither fasting nor non-fasting administrations of high-dose oral RIF achieve the therapeutic aims. More research is needed in larger populations and with measuring the amount of protein-unbound RIF levels.

LipoxinA4 (LXA4) is an anti-inflammatory biomarker participating in the active process of inflammation resolution, which is suggested to be effective on infectious and inflammatory diseases like COVID-19. In this study, we hypothesized that LXA4 levels may increase following COVID-19 treatment and are even more accurate than commonly used inflammatory markers such as erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), and ferritin. To test this hypothesis, a pilot study was conducted with 31 adult hospitalized patients with non-severe COVID-19. LXA4 levels were measured at the baseline and 48-72 hours later. Accordingly, ESR and CRP levels were collected on the first day of hospitalization. Moreover, the maximum serum ferritin levels were collected during the five days. LXA4 levels significantly increased at 48-72 hours compared to the baseline. ESR, CRP, and ferritin levels were positively correlated with the increased LXA4. In contrast, aging was shown to negatively correlate with the increased LXA4 levels. LXA4 may be known as a valuable marker to assess the treatment response among non-elderly patients with non-severe COVID-19. Furthermore, LXA4 could be considered as a potential treatment option under inflammatory conditions. Further studies are necessary to clarify LXA4 role in COVID-19 pathogenesis, as well as the balance between such pro-resolving mediators and inflammatory parameters.

Purpose: Although the current widespread use of amikacin is in intra-abdominal sepsis treatment, its pharmacokinetic changes in the present setting are not yet well known. This study was aimed to evaluate the amikacin pharmacokinetic profile in critically ill patients with intraabdominal sepsis compared to pneumosepsis. Methods: Adult septic patients received amikacin therapy were studied. Patients with intraabdominal sepsis were enrolled in group 1 (n=16), and patients with pneumosepsis were enrolled in group 2 (n=13). The amikacin serum concentrations were evaluated in the first, second, fourth and sixth hours after initiating 30-minute infusion. The pharmacokinetic parameters were calculated for each patient. Results: There was no significant difference in the volume of distribution between the two groups (0.33±0.08 vs. 0.28±0.10 L/kg, P=0.193). The amikacin clearance was significantly lower in group 1 compared to group 2 (58.5±21.7 vs. 83.9±37.0 mL/min, P=0.029). There was no significant correlation between amikacin clearance and creatinine clearance estimated by Cockcroft-Gault formula in all patients (P=0.206). The half-life was significantly longer in group 1 compared to group 2 (5.3±2.8 vs. 3.4±3.2 hours, P=0.015). Conclusion: Pathophysiologic changes following intra-abdominal sepsis can affect amikacin pharmacokinetics behavior. The clearance and half-life may change, but the alteration of the volume of distribution is not significantly different in comparison with pneumosepsis. Further studies are required to evaluate the pharmacokinetic variables of amikacin in critically ill patients with intra-abdominal sepsis.

Background: Since the outbreak of coronavirus 2019 (COVID-19), identifying risk factors associated with in-hospital mortality has been a global priority. In this study, the purpose was to evaluate the clinical, laboratory, and radiological characteristics of hospitalized patients with COVID-19 to develop a predictive model and scoring system for in-hospital mortality. Methods: In this retrospective cohort study, 611 adult patients with COVID-19, admitted to Sina hospital were enrolled and followed up. Results: Out of the total number of 611 patients, 104 patients (17%) deceased during hospitalization, including 75 (12.2%) deaths in ICU and 29 (4.7%) deaths in the wards. After multivariate logistic regression analysis, several characteristics including age >55 years, previous history of malignancy, history of cerebrovascular accident, tachypnea on admission, CRP>54 on admission, D-dimer>1300, and bilateral pulmonary consolidation on chest Computed Tomography (CT) were shown to be the main determinants for stratifying the risk for in-hospital death. The factors were finally considered for introducing a new predictive scoring system for COVID-19 related death. Conclusion: In-hospital mortality rate in patients with COVID-19 is estimated to be 17%. A new scoring system for predicting in-hospital mortality in such patients was structured based on determinant factors of advanced age, history of malignancy, cerebrovascular accident, tachypnea, raised CRP, raised D-dimer on admission, and bilateral pulmonary consolidation on chest CT scan.

Pharmacotherapy is an essential strategy for the treatment of many medical conditions especially chronic disease and often involves multiple medications being used simultaneously. Increasing the use of medications may pose some challenges to safe and effective drug therapy and if not identified and prevented by the pharmacists eventually can lead to drug-related problems (DRPs). The present study aimed to examine the incidence of DRPs in Iranian patients and to evaluate patients' adherence to the clinical pharmacist interventions as well as the physicians' acceptance of these recommendations.This study was conducted in a university-affiliated outpatient pharmacotherapy clinic over a 22-month period. Patients aged 18 years and older with at least one chronic disease receiving at least four medications were included in the study. The patients were interviewed by a clinical pharmacist for comprehensive medication review. DRPs were identified using the DOCUMENT classification system. Recommendations were provided by the clinical pharmacist including interventions involving patient and/or physician to resolve DRPs. The patients were followed up after 2 weeks to evaluate their compliance and physician acceptance of clinical pharmacist recommendations.Two hundred patients were included in this study. Overall, 875 DRPs were identified with an average of 4.37 per patient. The most prevalent DRPs were related to patient education or information (22.8%), undertreated indications (17.4%) and patient compliance (17.2%). The most common drugs associated with DRPs were alimentary and metabolism (22.2% of DRPs) followed by the cardiovascular system (19.2%) and nervous system (9.6%) medications. The DRP incidence correlated with gender only and was higher in females (p = 0.019). The clinical pharmacist provided 912 interventions with an average of 4.56 and 1.04 interventions per patient and per DRPs respectively. Patient education (41.3%), medication initiation or discontinuation (24.5%), and non-pharmacological interventions (12.9%) were the most common clinical pharmacist interventions. Out of 912 interventions, 665 were followed up, out of which 427 were patient dependent and 228 involved physicians. The patient's compliance with clinical pharmacist recommendations was 81.2%. The physician acceptance rate of the recommendations was 44.1%.The study shows that especially designed services such as pharmacotherapy clinics running by clinical pharmacists are necessary to detect and resolve DRPs in an effective way. The high compliance rate of the patients indicates patients' confidence in the clinical pharmacist services provided in the pharmacotherapy clinic. The low acceptance rate of the physicians highlights the need to improve interprofessional collaboration between clinical pharmacists and physicians in an outpatient setting.

OBJECTIVES: This study aimed to evaluate the relationship between amikacin pharmacokinetics and the biomarkers associated with organ dysfunction in critically ill patients with intra-abdominal sepsis. METHODS: A case series involving critically ill patients with intra-abdominal sepsis who received an amikacin loading dose of 20–25 mg/kg intravenous infusion was studied. The 1-, 2-, 4-, 6- and 24-hour amikacin serum concentrations were measured to calculate the pharmacokinetic parameters. The Sequential Organ Failure Assessment (SOFA) score, white blood cells, neutrophil to lymphocyte ratio, platelet count, serum creatinine, creatinine clearance, bilirubin, partial pressure of oxygen to fraction of inspired oxygen ratio, serum albumin, procalcitonin, lactate level, erythrocyte sedimentation rate (ESR) and C-reactive protein were recorded. A linear regression analysis was performed to examine the relationship between the amikacin pharmacokinetics and the biological parameters. RESULTS: Twenty-one patients were studied. A significant correlation was found between the volume of distribution and ESR (p

Background Keeping the heart rate within the normal range has improved the survival of septic shock patients. Amiodarone could target the underlying pathophysiology of sepsis-induced tachycardia. This study aimed to determine whether amiodarone is effective in controlling the heart rate in critically ill patients with septic shock and sustained tachycardia who were receiving vasopressor. Methods In this prospective, single-arm cohort study, 46 patients with septic shock and tachycardia were enrolled to receive a loading dose of amiodarone 150 mg, then continuous infusion of 1 mg/min. The primary outcome was the ability of amiodarone in rate control lower than 95 beats per minute (BPM) and maintaining it during 24-h study period. We also recorded the effect of amiodarone on hemodynamic indices as the secondary outcomes. Results The results of the present study indicated a significant decrease in HR in septic shock patients for amiodarone, from 121.0 (116.5, 140.0) at baseline to 91.5(89.3, 108.0) at the end of the study period (p P Conclusion This study showed that amiodarone infusion successfully reduced the heart rate in sepsis-induced tachycardia. The patients had improved hemodynamic state as indicated by an increase in cardiac index and SVI.

Objectives Amikacin is still a widely used aminoglycoside for the treatment of life-threatening infections. The pharmacokinetic parameters of this antibiotic may be altered in critically ill conditions. Moreover, in the elderly population, pathophysiological changes affect these pharmacokinetic variables, making it difficult to predict the appropriate dose and dosing schedule for amikacin. This study aimed to characterise the pharmacokinetics of amikacin in critically ill elderly patients with renal dysfunction, and to evaluate if the available dose adjustment schedules dependent on renal function would be appropriate for empirical dosing. Methods Critically ill patients aged >60 years with a creatinine clearance of >20 mL/min in need of treatment with amikacin were randomly enrolled. All the patients received approximately 25 mg/kg amikacin. The patients were then divided into three groups according to the stages of their renal dysfunction based on creatinine clearance, and the optimum time to re-dosing was calculated for each group. The pharmacokinetic parameters of the patients were calculated and estimated as population pharmacokinetic data. Results Of 30 patients, only 20% attained the target peak levels of amikacin of >64 mg/L. In addition, the mean volume of distribution was 0.47 L/kg. There was a poor correlation between amikacin clearance and creatinine clearance. The difference in amikacin half-life was not statistically significant among any of the stages of renal impairment. Conclusions The initial dosing of amikacin in critically ill elderly patients should not be reduced, even in the context of renal impairment. Regarding the dose adjustment in renal impairment, dosing intervals estimation, no decision can be made based on the creatinine clearance and the first dose individualisation method in terms of the two-sample measurements may be considered as an appropriate strategy.

What is known and objective Sepsis is a life-threatening organ dysfunction associated with a high rate of morbidity and mortality. Appropriate antibiotic therapy remains the cornerstone of sepsis and septic shock management. Comment Although the early initiation of antimicrobial agents in the treatment of sepsis is widely acknowledged, the selection and adjustment to optimal dosage can be equally important. Since significant pathophysiological changes in the critically ill patients lead to altered pharmacokinetics of antibiotics, early consideration of pharmacokinetic/pharmacodynamic (PK/PD) properties is necessary for optimal antibiotic dosing in sepsis and should be integrated in practice. What is new and conclusion Where possible, an individualized antibiotic dosing approach through the application of therapeutic drug monitoring (TDM) service should replace the conventional dosing in critically ill patients with sepsis. Finally, antimicrobial stewardship can help improve clinical outcomes.

Background: Intracerebral hemorrhage (ICH) is one of the most debilitating kinds of stroke. Recent evidence shows that the proper initiation of neuroprotective agents might save at risk neurons and improve the outcome. Objectives: The focus of this study is to evaluate the neuroprotective effect of melatonin on patients with hemorrhagic stroke. Methods: Forty adult patients with confirmed nontraumatic ICH, who were admitted to the ICU within 24 hours of the stroke onset were enrolled in this study. Subjects in the melatonin group received 30 mg of melatonin every night for 5 consecutive nights. In order to evaluate the intensity of the neuronal injury, S100B was assessed once on day 1 and, day 5 post ICU admission. Additionally, the length of ICU stay, mortality, and the duration of mechanical ventilation were also recorded. Results: Forty patients completed the study. In both groups the plasma concentrations of S100B decreased after 5 days compared with their baseline values. However, this reduction was more significant in the melatonin compared to the control group (P-value < 0.05). The duration of mechanical ventilation and length of ICU stay was shorter in the melatonin group, and this difference was statistically significant for the length of ICU stay (P-value < 0.05), and marginally significant for the duration of mechanical ventilation (P-value = 0.065). The in-ICU mortality rate of the melatonin group was 15%, almost half of that of the control group (30%). However, this difference was not statistically significant. Conclusions: In conclusion, melatonin can be considered as a harmless and effective nueroprotective agent with some unique features which has made it an appropriate adjunctive medicine for critically ill intubated patients.

Background: Methadone is used for the pain management worldwide. Its special characteristics make it a potential alternative for pain management in critically ill and geriatric patients. Due to lack of studies in this population, we aimed to compare the pharmacokinetic behavior of Methadone following intramuscular and intravenous administration in geriatric ICU patients and with previously reports in healthy volunteers. Methods: According to the limitations in ICU setting, we could include 11 patients over 65 years old, who required opioid for pain relief in this study. Patients were randomized to receive 5 mg of Methadone IM or IV injection every 8 hours for 6 days. The Methadone plasma level detected with LC-mass tandem mass spectrometry, and pharmacokinetics parameters were evaluated for each subject in both 1st and 6th days of treatment. Results: Based on our results, bioavailability of intramuscular Methadone in geriatric ICU patients was low and less than 40% of the dose was absorbed within first 12 hours. The volume of distribution of Methadone in the first day was significantly lower than the previously reported values in healthy subjects and significantly increased during these 6 days. The Methadone half-life in this population also significantly increased through this period. Conclusion: Pharmacokinetic behavior of Methadone in geriatric ICU patients is unpredictable. Reduced volume of distribution and half-life may be observed initially, following with an increase to the normal range. It seems that IM administration of Methadone in geriatric critically ill patients may not provide target analgesic Methadone serum levels.

A new corona virus disease (COVID-19) has affected more than 17 million people worldwide so far, and has become a global pandemic. Since there is no definitive cure for this life threatening disease, many clinical studies are in progress in this regard. Pathogen-associated molecular patterns (PAMP) prompting by coronavirus seems to generate cellular, structural, and functional derangements induced by immune dysregulation as well as many biological abnormalities including cytokine storm. The role of IL-6 in viral pneumonia and also its inhibition impact on the prevention of organ damage are still unknown.IL-6 seems to behave as a double blade evil cytokine, by playing a valuable role in cell to cell natural physiological communication. Tocilizumab, as an inhibitor of interleukin (IL)-6, may interrupt the paracrine system while causing dissemination of bacterial, fungal, and other viral infections, especially COVID-19, who are at a high-risk for development of sepsis and life-threatening superinfection.

The novel coronavirus 2019-nCoV (SARS-CoV-2) infection that emerged in China in December 2019 has rapidly spread to become a global pandemic. This article summarizes the potential benefits of erythropoietin (EPO) in alleviating SARS-CoV-2 pathogenesis which is now called COVID-19. As with other coronavirus infection, the lethality of COVID-19 is associated with respiratory dysfunction due to overexpression of proinflammatory cytokines induced by the host immune responses. The resulting cytokine storm leads to the development of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Erythropoietin, well known for its role in the regulation of erythropoiesis, may have protective effects against ALI/ARDS induced by viral and other pathogens. EPO exerts antiapoptotic and cytoprotective properties under various pathological conditions. With a high safety profile, EPO promotes the production of endothelial progenitor cells and reduce inflammatory processes through inhibition of the nuclear factor-κB (NF-κB) and JAK-STAT3 signaling pathways. Thus, it may be considered as a safe drug candidate for COVID-19 patients if given at the early stage of the disease. The potential effects of erythropoietin on different aspects of ALI/ARDS associated with SARS-CoV-2 infection are reviewed.

BACKGROUNDThere is an ongoing controversy about harms and benefits of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in hypertensive patients with coronavirus disease 2019 (COVID-19). Given the unresolved debate, we investigated the association of ARBs with in-hospital outcomes of these patients.METHODSIn this retrospective observational study, we studied patients with COVID-19 who referred to Sina Hospital in Tehran, Iran, from 20 February to 29 May 2020. Patients with either positive real-time reverse-transcriptase polymerase-chain-reaction test of swab specimens, or high clinical suspicion according to the World Health Organization’s interim guidance were included. We followed-up patients for incurring death, severe COVID-19, and in-hospital complications.RESULTSWe evaluated 681 patients with COVID-19 of whom 37 patients were excluded due to incomplete medical records and 8 patients who used ACEIs which left 636 patients in the analysis. In this cohort, 108 (17.0%) patients expired and 407 (64.0%) patients incurred severe COVID-19. Of 254 (39.9%) patients with hypertension, 122 (48.0%) patients were receiving an ARB. After adjustment for possible confounders, we found no independent association between taking ARBs and in-hospital outcomes except for acute kidney injury (AKI), in patients with confirmed or clinically suspected COVID-19, either hypertensive or not-hypertensive. We found that discontinuation of ARBs during hospitalization was associated with a greater risk of mortality, invasive ventilation, and AKI (all P ˂ 0.002).CONCLUSIONSWe found that taking ARBs by patients with hypertension and confirmed or clinically suspected COVID-19 is not associated with poorer in-hospital outcomes after adjustment for possible confounders.

Introduction: Since December 2019, an outbreak of Covid-19 has imposed growing worldwide concern. Researchers around the world is working to find a treatment or a vaccine for the Covid-19 and different treatment approaches have been tested in this regard. Objective: This study was designed and conducted to assess the possible efficacy of Interferon beta-1a as a a safe and efficient candidate for Covid-19 treatment. Methods: This is an investigator-initiated, open label, single arm clinical trial. Twenty suspected patients with Covid-19 who were admitted from 6 to 10 March, 2020 at Sina hospital in Tehran, Iran with moderate to severe symptoms were enrolled. Patients were treated with antiviral and hydroxychloroquine combination therapy with addition of subcutaneous Interferon beta-1a for 5 consecutive days. Baseline charactristiv and findings during the course of admission and 5 days after discharge were recorded for all the patients. Results: Totally, 20 patients with suspected Covid-19, were participated in this study, of whom 12 patients (60%) were male. The median (IQ) of patients’ age was 55.5 (43-63.5). The most common symptom of the patients at onset of disease was fever. The median (Interquartile, IQ range) days of hospital stay was 5.0 (3-6) days. Only 2 cases were admitted to ICU. At the time of follow-up, 15 (94%) patients reported that they generally feel good and had oral tolerance, 1 patient had suffered from dyspnea, 5 patients had suffered from cough, none of them had experienced fever and no case of re-admission or death was reported after discharge. Conclusions: Results of current study are in favor of using Interferon beta-1a in addition to recommended antiviral treatment in Covid-19 patients.

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. J Pharm Care 2020; 8(1): 3-10.