Evaluation of short-term adverse events of COVID-19 vaccines: An observational study.

Coronavirus disease 2019 (COVID-19) vaccines are the most effective tools in managing the pandemic. However, the concern about these vaccines is the occurrence of unwanted adverse events (AEs). This study aimed to evaluate the short-term AEs of COVID-19 vaccines (Sputnik V, Astrazenka, and Sinopharm). A cross-sectional study using an online questionnaire was conducted among 321 vaccinated individuals. Demographic information, history of drug use, prior infection with COVID-19, the type of vaccine, vaccination stage, local injection site complication, systemic complication, and allergic reactions were collected and evaluated. Local complications, including pain and swelling at the injection site, and systemic complications, including fever, fatigue, lethargy, lymphadenopathy, and diarrhea, were reported after the injection of the AstraZeneca vaccine was more than the other 2 vaccines; The prevalence of fatigue and lethargy was higher than other systemic complications. The least reported complication was due to lymphadenopathy. The Sinopharm vaccine showed a lower prevalence of AEs than the other 2. The rare AEs, such as facial paralysis, nasal bleeding, and urticarial, were further reported after injection of the AstraZeneca vaccine. In general, the severity of systemic complications after the second dose of the vaccine was also higher than the first dose. All 3 vaccines were safe and tolerable. The most commonly reported AEs were injection site pain (local) and fatigue and lethargy (systemic). These expected AEs occurred shortly after vaccination and indicated an early immune response after vaccination.

Efficacy and safety of licorice (Glycyrrhiza glabra) in moderately ill patients with COVID-19: a randomized controlled trial.

Licorice extract (glycyrrhizin), a potent antiviral, anti-inflammatory, and antioxidant remedy, is a potential therapeutic option for COVID-19. We evaluated the efficacy and safety of licorice in patients with moderate COVID-19. In this study, 60 patients with confirmed COVID-19 were randomly assigned in a 1:1 ratio to receive licorice (at a dose of 760 mg three times a day for seven days) or control groups. The primary outcomes were SPO2, body temperature, and respiratory rate (RR) after the end of the intervention. The findings indicated that SPO2, body temperature, and RR had no significant difference between the groups at the end of the intervention. However, CRP and ALT improved in the licorice group toward the baseline. The number of patients with worse prognoses, LOS, mortality, and the incidence of adverse events were not different between the groups at the end of the study. Licorice had no beneficial effect on the clinical symptoms of COVID-19. Moreover, this intervention demonstrated a safe profile of adverse events. The confirmation of the results of this preparatory trial requires more detailed multiple-center trials with a larger sample size.

Efficacy and safety of oral melatonin in patients with severe COVID-19: a randomized controlled trial.

Patients with COVID-19 have shown melatonin deficiency. We evaluated the efficacy and safety of administration oral melatonin in patients with COVID-19-induced pneumonia. Patients were randomly assigned in a 1:1 ratio to receive melatonin plus standard treatment or standard treatment alone. The primary outcomes were mortality rate and requirement of IMV. The clinical status of patients was recorded at baseline and every day over hospitalization based on seven-category ordinal scale from 1 (discharged) to 7 (death). A total of 226 patients (109 in the melatonin group and 117 in the control group) were enrolled (median age; in melatonin group: 54.60 ± 11.51, in control group: 54.69 ± 13.40). The mortality rate was 67% in the melatonin group and 94% in the control group (OR; 7.75, 95% CI, 3.27-18.35, P < 0.001). The rate of IMV requirement was 51.4% in the melatonin group and 70.9% in the control group, for an OR of 2.31 (95% CI, 1.34-4.00, P < 0.001). The median number of days to hospital discharge was 15 days (13-17) in the melatonin group and 21 days (14-24) in the control group (OR; 5.00, 95% CI, 0.15-9.84, P = 0.026). Time to clinical status improvement by ≥ 2 on the ordinal scale in was 12 days (9-13) in the melatonin group and 16 days (10-19) in the control group (OR; 3.92, 95% CI, 1.69-6.14, P = 0.038). Melatonin significantly improved clinical status with a safe profile in patients with severe COVID-19 pneumonia.

The Efficacy, Safety, and Tolerability of Levofloxacin Quadruple Therapy for Helicobacter pylori Eradication: A Randomized, Double-Blind Clinical Trial.

The incidence of microbial resistance is growing, and new rescue regimens are needed to treat Helicobacter pylori (H. pylori) infection. This study aimed to evaluate levofloxacin-based quadruple therapies' efficacy, safety, and tolerability in eradicating H. pylori. In a randomized, double-blind clinical trial, 220 patients with dyspepsia and H. pylori infection were randomly assigned to receive either bismuth subcitrate 240 mg, pantoprazole 20 mg, amoxicillin 1000 mg twice a day, and levofloxacin 500 mg daily for seven days (BPAL-7) or ten days (BPAL-10). The eradication of H. pylori was evaluated two months after the end of treatment, and adverse drug reactions (ADRs) were assessed during the intervention. According to intention-to-treat and per-protocol, the eradication rate was significantly lower in the BPAL-7 regimen at 49.1% (95% CI: 39.3-57.8) and 47.6% (95% CI: 39.7-58.4), respectively, compared to the BPAL-10 regimen at 62.7% (95% CI: 53.6-72.8) and 62.4% (95% CI: 55.1-72.8), respectively. The ADR incidence was not statistically significant between the groups of BPAL-7 (33.6%) and BPAL-10 (36.7%). Although the ADRs were negligible in both groups, these regimens could not be an ideal alternative therapy for H. pylori because of their low eradication rates compared to standard regimens. Trial Registration. The study was reviewed and approved by the Iranian Registry of Clinical Trials (IRCT201406141155N19).

Efficacy and safety of favipiravir plus interferon-beta versus lopinavir/ritonavir plus interferon-beta in moderately ill patients with COVID-19: A randomized clinical trial.

Favipiravir (FVP), lopinavir/ritonavir (LPV/RTV), and interferon-beta (INF-beta) are considered as potential treatments for COVID-19. We examined the efficacy and safety of FVP and INF-beta compared to LPV/RTV and INF-beta combinations for the treatment of SARS-CoV-2. It was a single-center randomized clinical trial. Eligible patients were randomized to receive FVP plus INF-beta versus LPV/RTV plus INF-beta. The primary endpoint was the viral clearance after seven days of randomization. ICU admission, length of stay (LOS) in hospital, in-hospital mortality, and the incidence of adverse events were also measured. This trial was registered on the Iranian Registry of Clinical Trials (IRCT20200506047323N3). Patients were randomly allocated to the FVP (n = 33) and LPV/RTV (n = 33) groups. The viral clearance on Day seven was not significantly different between the FVP (31.1%) and the LPV/RTV groups (16.1%). The rate of ICU admission and likewise the in-hospital mortality in the FVP group (12.5% and 6.3%, respectively) were similar to the LPV/RTV groups (19.4% and 19.4%, respectively). The median LOS in the hospital was also not different (6.8 days [interquartile range; IQR = 5.0-11.0] in the FVP and (8.0 days [IQR = 5.5-12.5]) in LPV/RTV groups (p = 0.140). Adverse events were observed in 25.0% of FVP and 32.3% of LPV/RTV groups. The combination therapy with FVP did not exert a higher efficacy compared to the combination regimen of LPV/RTV. However, both treatment regimens demonstrated a mild profile of adverse events.

Therapeutic Effects of Milk Thistle (Silybum marianum L.) and Artichoke (Cynara scolymus L.) on Nonalcoholic Fatty Liver Disease in Type 2 Diabetic Rats.

BACKGROUND: At present, nonalcoholic fatty liver disease (NAFLD) does not have an approved pharmacologic therapy. The present study investigated the protective effects and possible mechanisms of milk thistle (Silybum marianum L.) and artichoke (Cynara scolymus L.) in treating NAFLD in type 2 diabetic rats. METHODS: The NAFLD was established in rats after four weeks of type 2 diabetes induction. The animals were treated with pharmaceutical preparations of milk thistle (Livergol®) and artichoke (Atheromod-B®) extracts for eight weeks. After the end of the intervention, oral glucose tolerance, the serum parameters of oxidative stress, liver functional tests, and lipid profiles were evaluated. Histopathological changes were assessed by hematoxylin and eosin staining. RESULTS: Treatment with preparations of milk thistle and artichoke nonsignificantly improved glucose tolerance in diabetic rats. Both preparations significantly improved serum superoxide dismutase activity and the level of malondialdehyde. Although treatment with milk thistle reduced serum activity of aspartate aminotransferase and serum levels of triglyceride (TG), total cholesterol, and low-density lipoprotein-cholesterol, artichoke extracts only attenuated the serum level of TG. Milk thistle also effectively protected the liver from histological changes. CONCLUSIONS: Milk thistle could be a promising pharmacological option for the treatment of NAFLD. Nonetheless, long-term randomized clinical trials are necessary to confirm the observed results.

A triple-blind, placebo-controlled, randomized clinical trial to evaluate the effect of curcumin-containing nanomicelles on cellular immune responses subtypes and clinical outcome in COVID-19 patients.

In COVID-19 patients, cytokine storm due to excessive immune responses can cause severe complications. In this study, we investigated the effect of curcumin nanomicelles on clinical outcome and cellular immune responses subtypes changes in COVID-19 patients. A randomized, triple-blinded, placebo-controlled study was done. Forty COVID-19 patients were included into two groups of nano-curcumin and placebo. The nano-curcumin group received 40 mg of nano-curcumin capsule, four times per day for 2 weeks. Clinical signs and gene expression of TBX21, GATA3, RORC and FOXP3 genes and IFN-γ, IL-4, IL-17 and TGF-ß cytokines serum levels were measured at time points of 0, 7 and 14 days. Serum levels of IFN-γ (p = .52) and IL-17 (p = .11) decreased, while IL-4 (p = .12) and TGF-ß (p = .14) increased in the nano-curcumin group compared with placebo on day 14. Moreover, gene expressions of TBX21 (p = .02) and FOXP3 (p = .005) genes were significantly decreased and increased between nano-curcumin and placebo groups on day 7, respectively. It can be concluded that administration of nano-curcumin in inflammatory phase of COVID-19 can accelerate recovering of the acute inflammatory phase by modulating inflammatory immune responses. Therefore, it is suggested that this supplement in inflammatory diseases, including COVID-19, can be effective in controlling the inflammatory responses.

Potential inhibitors of the main protease of SARS-CoV-2 and modulators of arachidonic acid pathway: Non-steroidal anti-inflammatory drugs against COVID-19.

The main protease of SARS-CoV-2 is one of the key targets to develop and design antiviral drugs. There is no general agreement on the use of non-steroidal anti-inflammatory drugs (NSAIDs) in COVID-19. In this study, we investigated NSAIDs as potential inhibitors for chymotrypsin-like protease (3CLpro) and the main protease of the SARS-CoV-2 to find out the best candidates, which can act as potent inhibitors against the main protease. We also predicted the effect of NSAIDs on the arachidonic pathway and evaluated the hepatotoxicity of the compounds using systems biology techniques. Molecular docking was conducted via AutoDock Vina to estimate the interactions and binding affinities between selected NSAIDs and the main protease. Molecular docking results showed the presence of 10 NSAIDs based on lower binding energy (kcal/mol) toward the 3CLpro inhibition site compared to the co-crystal native ligand Inhibitor N3 (-6.6 kcal/mol). To validate the docking results, molecular dynamic (MD) simulations on the top inhibitor, Talniflumate, were performed. To obtain differentially-expressed genes under the 27 NSAIDs perturbations, we utilized the L1000 final Z-scores from the NCBI GEO repository (GSE92742). The obtained dataset included gene expression profiling signatures for 27 NSAIDs. The hepatotoxicity of NSAIDs was studied by systems biology modeling of Disturbed Metabolic Pathways. This study highlights the new application of NSAIDs as anti-viral drugs used against COVID-19. NSAIDs may also attenuate the cytokine storm through the downregulation of inflammatory mediators in the arachidonic acid pathway.

Comprehensive analysis of diabetic nephropathy expression profile based on weighted gene co-expression network analysis algorithm.

BACKGROUND: Diabetic nephropathy (DN) is the major complication of diabetes mellitus, and leading cause of end-stage renal disease. The underlying molecular mechanism of DN is not yet completely clear. The aim of this study was to analyze a DN microarray dataset using weighted gene co-expression network analysis (WGCNA) algorithm for better understanding of DN pathogenesis and exploring key genes in the disease progression. METHODS: The identified differentially expressed genes (DEGs) in DN dataset GSE47183 were introduced to WGCNA algorithm to construct co-expression modules. STRING database was used for construction of Protein-protein interaction (PPI) networks of the genes in all modules and the hub genes were identified considering both the degree centrality in the PPI networks and the ranked lists of weighted networks. Gene ontology and Reactome pathway enrichment analyses were performed on each module to understand their involvement in the biological processes and pathways. Following validation of the hub genes in another DN dataset (GSE96804), their up-stream regulators, including microRNAs and transcription factors were predicted and a regulatory network comprising of all these molecules was constructed. RESULTS: After normalization and analysis of the dataset, 2475 significant DEGs were identified and clustered into six different co-expression modules by WGCNA algorithm. Then, DEGs of each module were subjected to functional enrichment analyses and PPI network constructions. Metabolic processes, cell cycle control, and apoptosis were among the top enriched terms. In the next step, 23 hub genes were identified among the modules in genes and five of them, including FN1, SLC2A2, FABP1, EHHADH and PIPOX were validated in another DN dataset. In the regulatory network, FN1 was the most affected hub gene and mir-27a and REAL were recognized as two main upstream-regulators of the hub genes. CONCLUSIONS: The identified hub genes from the hearts of co-expression modules could widen our understanding of the DN development and might be of targets of future investigations, exploring their therapeutic potentials for treatment of this complicated disease.

The efficacy and safety of Favipiravir in treatment of COVID-19: a systematic review and meta-analysis of clinical trials.

The novel coronavirus outbreak began in late December 2019 and rapidly spread worldwide, critically impacting public health systems. A number of already approved and marketed drugs are being tested for repurposing, including Favipiravir. We aim to investigate the efficacy and safety of Favipiravir in treatment of COVID-19 patients through a systematic review and meta-analysis. This systematic review and meta-analysis were reported in accordance with the PRISMA statement. We registered the protocol in the PROSPERO (CRD42020180032). All clinical trials which addressed the safety and efficacy of Favipiravir in comparison to other control groups for treatment of patients with confirmed infection with SARS-CoV2 were included. We searched electronic databases including LitCovid/PubMed, Scopus, Web of Sciences, Cochrane, and Scientific Information Database up to 31 December 2020. We assessed the risk of bias of the included studies using Cochrane Collaboration criteria. All analyses were performed using the Comprehensive Meta-Analysis software version 2, and the risk ratio index was calculated. Egger and Begg test was used for assessing publication bias. Nine studies were included in our meta-analysis. The results of the meta-analysis revealed a significant clinical improvement in the Favipiravir group versus the control group during seven days after hospitalization (RR = 1.24, 95% CI: 1.09-1.41; P = 0.001). Viral clearance was more in 14 days after hospitalization in Favipiravir group than control group, but this finding marginally not significant (RR = 1.11, 95% CI: 0.98-1.25; P = 0.094). Requiring supplemental oxygen therapy in the Favipiravir group was 7% less than the control group, (RR = 0.93, 95% CI: 0.67-1.28; P = 0.664). Transferred to ICU and adverse events were not statistically different between two groups. The mortality rate in the Favipiravir group was approximately 30% less than the control group, but this finding not statistically significant. Favipiravir possibly exerted no significant beneficial effect in the term of mortality in the general group of patients with mild to moderate COVID-19. We should consider that perhaps the use of antiviral once the patient has symptoms is too late and this would explain their low efficacy in the clinical setting.

Epidemiology and risk factors of needlestick injuries among healthcare workers in Iran: a systematic reviews and meta-analysis.

BACKGROUND: Occupational contact with blood and body fluids poses a significant risk to healthcare workers. The aim of this systematic review is to investigate the epidemiology and risk factors affecting needlestick injuries (NSI) in healthcare personnel in Iran. METHODS: In March 2020, researchers studied six international databases such as Medline/PubMed, ProQuest, ISI/WOS, Scopus, Embase, and Google Scholar for English papers and two Iranian databases (MagIran and SID) for Persian papers. Joanna Briggs Institute (JBI) Critical Appraisal Checklist was used to assess quality of studies. The method of reporting was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. RESULTS: A total of 43 articles were included in the analysis. Results showed that females (OR = 1.30, 95 % CI 1.06-1.58, P value = 0.009), younger age (OR = 2.75, 95 % CI 2.27-3.33, P value < 0.001, rotated shift workers (OR = 2.16, 95 % CI 1.47-3.15, P value < 0.001), not attending training courses (OR = 1.30, 95 % CI 1.07-1.56, P value = 0.006), working in the surgery ward (OR = 1.83, 95 % CI 1.33-2.50, P value < 0.001), less work experience (OR = 1.43, 95 % CI 1.04-1.95, P value = 0.025) apposed a greater risk factors for NSI among healthcare workers. CONCLUSION: Based on the results of this review, factors such as young age, less work experience, work shift, and female gender are considered as strong risk factors for NSI injury in Iran. Preventive measures including education programs can reduce the burden of NSI among healthcare personnel.

Evaluation of the effect of melatonin in patients with COVID-19-induced pneumonia admitted to the Intensive Care Unit: A structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: We investigate the effects of melatonin, compared to the usual therapeutic regimen on clinical symptoms and laboratory signs in severely ill patients with confirmed COVID-19 who are admitted to the Intensive Care Unit (ICU). TRIAL DESIGN: This is a single-center, open-label, randomized, clinical trial with a parallel-group design. This study is being conducted at Shahid Mohammadi Hospital, Bandar Abbas, Iran. PARTICIPANTS: All patients admitted to the ICU of Shahid Mohammadi Hospital, Bandar Abbas, Iran, will be screened for the following criteria. Inclusion criteria 1. Age >20 years 2. Definitive diagnosis of COVID-19 based on RT-PCR or/and serological testing 3. Severe pneumonia and lung involvement in imaging 4. Signing informed consent Exclusion criteria 1. Underlying diseases, including convulsive disorders, chronic hepatic and renal diseases 2. Use of mechanical ventilation 3. History of known allergy to Melatonin 4. Pregnancy and breastfeeding INTERVENTION AND COMPARATOR: Intervention group: The standard treatment regimen for COVID-19, according to the Iranian Ministry of Health and Medical Education's protocol, along with Melatonin soft gelatin capsule (Danna Pharmaceutical Company) at a dose of 5 mg twice a day for a period of seven days. CONTROL GROUP: The standard treatment for COVID-19 based on the Iranian Ministry of Health and Medical Education's protocol for a period of seven days. MAIN OUTCOMES: The primary outcomes are the recovery rate of clinical symptoms and checking arterial blood gas (ABG), C-reactive protein (C-RP), Ferritin, Lactate dehydrogenase (LDH) within seven days of randomization. The secondary outcomes are time to improvement of clinical and paraclinical features and length of stay in the ICU, need for mechanical ventilation, and mortality rate within seven days of randomization. RANDOMIZATION: Included patients will be allocated to one of the study arms using block randomization in a 1:1 ratio (each block consists of 6 patients). This randomization method ensures a balanced allocation between the arms during the study. A web-based system will generate random numbers for the allocation sequence and concealment of participants. Each number relates to one of the study arms. BLINDING (MASKING): This is an open-label trial without blinding and placebo control. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): A total of 60 participants randomizes (30 patients allocated to the intervention group and 30 patients allocated to the control group). TRIAL STATUS: The protocol is Version 1.0, February 16, 2021. Recruitment began February 28, 2021, and is anticipated to be completed by July 31, 2021. TRIAL REGISTRATION: The trial protocol has been registered in the Iranian Registry of Clinical Trials (IRCT). The registration number is " IRCT20200506047323N7 ". The registration date was February 16, 2021. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Epidemiologic profile of viral hepatitis B and C in North of Iran: results from PERSIAN Guilan Cohort Study (PGCS).

OBJECTIVE: Hepatitis B (HB) and C (HC) are two severe viral infectious diseases with a deleterious impact on global health. This study aimed to evaluate the prevalence of HB and HC in the Prospective Epidemiological Research Studies of the Iranian Adults (PERSIAN) Guilan Cohort Study using immunological and molecular methods. RESULTS: The blood samples were obtained from 10,520 enrolled participants. Complete biochemical and hematological tests, as well as urine analysis, were assessed. The presence of HBsAg, anti-HBs, anti-HBc, and anti-HCV antibodies for all participant and HBeAg and anti-HBe antibodies for HB-positive patients were evaluated. Moreover, HB genomic DNA and HC genomic RNA were extracted from serum samples of HB-positive patients. The real-time PCR assay was employed to quantify the gene copies of hepatitis B and C viruses. HC genotyping was also performed. The prevalence of HB and HC was 0.24% (95% CI 0.16-0.35) and 0.11% (95% CI 0.06-0.19), respectively. Rural participants were significantly more HB-positive than the urban people (P = 0.045), while males were significantly more HC-positive than the females (P = 0.013). The prevalence of HB and HC in this area were lower than those of other geographical locations of Iran, which may be due to different lifestyles or other unknown reasons.

The efficacy and safety of Ivermectin in patients with mild and moderate COVID-19: A structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: We will evaluate the efficacy and safety of Ivermectin in patients with mild and moderately severe COVID-19. TRIAL DESIGN: This is a phase 3, single-center, randomized, open-label, controlled trial with a 2-arm parallel-group design (1:1 ratio). PARTICIPANTS: The Severe Acute Respiratory Syndrome Departments of the Shahid Mohammadi Hospital, Bandar Abbas, Iran, will screen for patients age ≥ 20 years and weight ≥35 kg for the following criteria: Inclusion criteria for patients with mild COVID-19 symptoms (outpatients) 1. Diagnosed mild pneumonia using computed tomography (CT) and/or chest X-ray (CX-R) imaging, not requiring hospitalization. 2. Signing informed consent. Inclusion criteria for patients with moderate COVID-19 symptoms (inpatients) 1. Confirmed infection using PCR. 2. Diagnosed moderate pneumonia using CT and/or CXR imaging, requiring hospitalization. 3. Hospitalized ≤ 48 hours. 4. Signing informed consent. Exclusion criteria 1. Severe and critical pneumonia due to COVID-19. 2. Underlying diseases, including AIDS, asthma, loiasis, and severe liver and kidney disease. 3. Use of anticoagulants (e.g., warfarin) and ACE inhibitors (e.g., captopril). 4. History of drug allergy to Ivermectin. 5. Pregnancy or breastfeeding. INTERVENTION AND COMPARATOR: Intervention groups: Outpatient and inpatient groups will receive the standard treatment regimen for mild and moderate COVID-19, based on the Iranian Ministry of Health and Medical Education's protocol, along with oral Ivermectin (MSD Company, France) at a single dose of 0.2 mg/kg. Control groups: The outpatient group will receive hydroxychloroquine sulfate (Amin Pharmaceutical Company, Iran) at a dose of 400 mg twice a day for the first day and 200 mg twice a day for seven subsequent days. The inpatient group will receive 200/50 mg Lopinavir/Ritonavir (Heterd Company, India) twice a day for the seven days, plus five doses of 44 mcg Interferon beta-1a (CinnaGen, Iran) every other day. Other supportive and routine care will be the same in both outpatient and inpatient groups. MAIN OUTCOME: The primary outcomes are composite and include the improvement of clinical symptoms and need for hospitalization for outpatient groups, and the length of hospital stay until discharge, the need for ICU admission until discharge, and the need for mechanical ventilation for inpatient groups within seven days of randomization. The secondary outcome is the incidence of serious adverse drug reactions within seven days of randomization. RANDOMIZATION: Patients in both outpatient (mild) and inpatient (moderate) groups will be randomized into the treatment and control groups based on the following method. A simple randomization method and table of random numbers will be used. If the selected number is even, the patient is allocated to the treatment group, and if it is odd, the patient is allocated to the control group in a 1:1 ratio. BLINDING (MASKING): This is an open-label study, and there is not blinding. Numbers to be randomized (sample size) A total number of 120 patients (60 outpatients and 60 patients) will be randomized into two groups (30 patients in each of the intervention groups and 30 patients in each of the control groups). TRIAL STATUS: The protocol is Version 1.0, November 17, 2020. Recruitment began November 25, 2020, and is anticipated to be completed by February 25, 2021. TRIAL REGISTRATION: This clinical trial has been registered in the Iranian Registry of Clinical Trials (IRCT). The registration number is " IRCT20200506047323N6 ". The registration date is November 17, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting the dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol.

Antibacterial Activity of Prunus Scoparia Root Methanol Extract against Most Common Burn Wound Pathogens.

BACKGROUND: Burn wound infection and sepsis are serious medical conditions requiring prompt intervention. Plants are a good natural source for the development of novel, safe, and cost-effective antibacterial agents. The objective of the present study was to assess the antibacterial potential of aqueous, chloroform, and methanol extracts of the Prunus scoparia (P. scoparia) root against the most common burn wound pathogens. METHODS: The present experimental study was conducted at Shiraz University of Medical Sciences (Shiraz, Iran) during 2018-2019. The antibacterial activity of the total plant extract was assayed using the broth microdilution method. Fractionation was performed using a separation funnel and solvents with different polarities. Broth microdilution and agar well diffusion assays were performed to determine the antibacterial potential of the obtained fractions. Quantitative and qualitative phytochemical analyses were performed to confirm the presence of secondary metabolites in both the total extract and the fractions. RESULTS: Methanolic extract of P. scoparia root exhibited antibacterial activity against all tested bacterial strains, especially against Methicillin-resistant Staphylococcus aureus (MRSA) isolates. This extract, compared to the aqueous and chloroformic extracts, exhibited the presence of active antibacterial compounds. The quantitative and qualitative results of phytochemical screening showed that phenols and flavonoids were the main antibacterial compounds in the methanolic extract of the plant. CONCLUSION: For the first time, we demonstrated the antibacterial activity of the P. scoparia root against MRSA isolates and other common burn wound pathogens.

The clinical effect of Nano micelles containing curcumin as a therapeutic supplement in patients with COVID-19 and the immune responses balance changes following treatment: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: To investigates the effectiveness of curcumin-containing Nanomicelles as a therapeutic supplement in the treatment of patients with COVID-19 and its effect on immune responses balance changes following treatment. TRIAL DESIGN: This study is conducted as a prospective, placebo-controlled with parallel group, single-center randomized clinical trial on COVID-19 patients. PARTICIPANTS: Patients are selected from the COVID-19 ward of Shahid Mohammadi Hospital in Bandar Abbas, Iran. INCLUSION CRITERIA: 1. Real time PCR-approved positive COVID-19 test. 2. Both gender 3. Age between 18 and 75 years 4. Signing a written consent 5. Lack of participation in other clinical trials Exclusion criteria: 1. Pregnancy or lactation 2. Allergy to turmeric or curcumin 3. Smoking 4. Patient connected to the ventilator 5. SaO2 less than 90% or PaO2 less than 8 kPa 6. Having comorbidities (such as severe renal failure, Glomerular filtration rate less than 30 ml/min, liver failure, Congestive heart failure, or Chronic obstructive pulmonary disease) 7. History of gallstones 8. History of gastritis or active gastrointestinal ulcer INTERVENTION AND COMPARATOR: In addition to the routine standard treatments for COVID-19, in the intervention group, 40mg nanomicelles containing curcumin (SinaCurcumin Capsule, Exir Nano Sina Company, Iran), four times per day (after breakfast, lunch, dinner and before bedtime) and in the placebo group as the control group, capsules with the same appearance and characteristics (Placebo capsules, Exir Nano Sina Company, Iran) are prescribed for two weeks. MAIN OUTCOMES: The effectiveness of Nano micelles containing curcumin treatment will be evaluated as daily clinical examinations of patients in both groups and, on days 0, 7 and 14, complete clinical symptoms and laboratory findings including peripheral blood and serum parameters such as inflammatory markers will be measured and recorded. Moreover, in order to evaluate the balance of immune responses changes following treatments, serum level of IFN-γ, IL-17, Il-4 and TGF-ß serum cytokines will be measured in both groups at time points of 0, 7 and 14 days post treatment. Gene expression of t-bet, GATA-3, FoxP3 and ROR- γT will also be measured at mentioned time points to assess the shift of T helper1, T helper2, T regulatory and T helper 17 immune responses following treatment. RANDOMISATION: Randomized trials will be performed on 40 COVID-19 patients which will be randomized using encoded sealed boxes with computer generated random digits with 1:1 allocation ratio. In order to randomization, placebo and SinaCurcumin Capsules will be numbered first by computer generated random digits. SinaCurcumin and placebo will then be stored and numbered in sealed packages based on generated random numbers. Finally, according to the order in which patients enter the study, packages are given to patients based on their number. BLINDING (MASKING): The present study will be blind for all patients, physicians and nurses, laboratory technicians and statisticians. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 40 patients will be included in the study, 20 of them will be randomly assigned to the intervention group and 20 to the placebo group. TRIAL STATUS: This is Version 1.0 of protocol dated 21 May 2020. The recruitment was started June 24, 2020 and is expected to be completed by October 31, 2020. TRIAL REGISTRATION: This present clinical trial has been registered in the Iranian Registry of Clinical Trials (IRCT) with the registration code of "IRCT20200611047735N1", https://www.irct.ir/trial/48843 . Dated: 19 June 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Evaluation of the efficacy and safety of Melatonin in moderately ill patients with COVID-19: A structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: We will evaluate the efficacy and safety of Melatonin, compared to the standard therapeutic regimen on clinical symptoms and serum inflammatory parameters in patients with confirmed COVID-19, who are moderately ill. TRIAL DESIGN: This is a single-center, randomized, double-blind, placebo-controlled clinical trial with a parallel-group design conducted at Shahid Mohammadi Hospital, Bandar Abbas, Iran. PARTICIPANTS: All patients admitted to Severe Acute Respiratory Syndrome Departments of Shahid Mohammadi Hospital, Bandar Abbas, Iran will be screened for the following criteria. INCLUSION CRITERIA: 1. Age ≥20 years 2. Confirmed SARS-CoV-2 diagnosis (positive polymerase chain reaction). 3. Moderate COVID-19 pneumonia (via computed tomography and or X-ray imaging), requiring hospitalization. 4. Hospitalized ≤48 hours. 5. Signing informed consent and willingness of the participant to accept randomization to any assigned treatment arm. EXCLUSION CRITERIA: 1. Underlying diseases, including chronic hypertension, diabetes mellitus, seizure, depression, chronic hepatitis, cirrhosis, and cholestatic liver diseases. 2. Severe and critical COVID-19 pneumonia. 3. Use of warfarin, corticosteroids, hormonal drugs, alcohol, other antiviral and investigational medicines, and illegal drugs (during the last 30 days). 4. History of known allergy to Melatonin. 5. Pregnancy and breastfeeding. INTERVENTION AND COMPARATOR: Intervention group: The standard treatment regimen for COVID-19, according to the Iranian Ministry of Health and Medical Education's protocol, along with Melatonin capsules at a dose of 50 mg daily for a period of seven days. CONTROL GROUP: The standard therapeutic regimen for COVID-19 along with Melatonin-like placebo capsules at a dose of one capsule daily for a period of seven days. Both Melatonin and placebo capsules were prepared at the Faculty of Pharmacy and Pharmaceutical Sciences, Hormozgan University of Medical Sciences, Bandar Abbas, Iran. MAIN OUTCOMES: The primary outcomes are the recovery rate of clinical symptoms and oxygen saturation as well as improvement of serum inflammatory parameters, including C-reactive protein, tumor necrosis factor-alpha (TNF-ɑ), interleukin-1ß (IL-1ß), and IL-6 within seven days of randomization. The secondary outcomes are the time to improve clinical and paraclinical features along with the incidence of serious adverse drug reactions within seven days of randomization. RANDOMIZATION: Included patients will be allocated to one of the study arms using block randomization in a 1:1 ratio (each block consists of 10 patients). This randomization method ensures a balanced allocation between the arms during the study. A web-based system will generate random numbers for the allocation sequence and concealment of participants. Each number relates to one of the study arms. BLINDING (MASKING): All study participants, clinicians, nurses, research coordinators, and those analyzing the data are blinded to the group assignment. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): A total of 60 patients randomized into two groups (30 in each group). TRIAL STATUS: The trial protocol is Version 1.0, August 14, 2020. Recruitment began August 22, 2020, and is anticipated to be completed by November 30, 2020. TRIAL REGISTRATION: The trial protocol has been registered in the Iranian Registry of Clinical Trials (IRCT). The registration number is " IRCT20200506047323N5 ". The registration date was 14 August 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Effects of Ginger on clinical manifestations and paraclinical features of patients with Severe Acute Respiratory Syndrome due to COVID-19: A structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: We investigate the effects of Ginger, compared to the usual therapeutic regimen on clinical manifestations and paraclinical features in patients with confirmed COVID-19 that are moderately ill. TRIAL DESIGN: This is a single center, randomized, double-blind, placebo-controlled clinical trial with parallel group design. PARTICIPANTS: Inclusion criteria: 1. Patients admitted to Severe Acute Respiratory Syndrome (SARS) Departments at Shahid Mohammadi Hospital, Bandar Abbas, Iran 2. Age ≥18 years (weight ≥35 kg) 3. Hospitalized ≤48 hours 4. Confirmed SARS-CoV-2 diagnosis (Positive polymerase chain reaction (PCR)) 5. Moderate pneumonia and lung involvement in imaging 6. Signing informed consent and willingness of study participant to accept randomization to any assigned treatment arm Exclusion criteria: 1. Underlying diseases, including heart disease, chronic hypertension, severe renal failure, severe liver failure, and thyroid disorders 2. Use of warfarin, selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), diuretics, corticosteroids, and antiarrhythmic drugs 3. Severe and critical pneumonia 4. History of known allergy to Ginger 5. Pregnancy and breastfeeding INTERVENTION AND COMPARATOR: Intervention group: The standard treatment regimen for COVID-19 along with Ginger-based herbal tablets (Vomigone ®, Dineh Pharmaceutical Company, Iran) at a dose of 1000 mg three times a day for a period of seven days. CONTROL GROUP: The standard treatment for COVID-19 based on the Iranian Ministry of Health and Medical Education's protocol, along with Vomigone-like placebo tablets (Dineh Pharmaceutical Company, Iran) at a dose of two tablets three times a day for a period of seven days. MAIN OUTCOMES: The primary outcome is recovery rate of clinical symptoms, including fever, dry cough, tiredness, and GI symptoms as well as paraclinical features, including thrombocytopenia, lymphocytopenia, and C-reactive protein within seven days of randomization. Time to improvement of clinical and paraclinical features along with the incidence of serious adverse events are the secondary outcomes within seven days of randomization. RANDOMIZATION: An interactive web-based system will be used to allocate eligible participants, based on the inclusion and exclusion criteria, to one of the two study arms (in a 1:1 ratio) using block randomization. BLINDING (MASKING): All study participants, research coordinators, clinicians, nurses, and investigators will be blinded to the group assignment. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): A total of 84 participants will be randomized into two groups of 42 patients. TRIAL STATUS: The protocol is Version 1.0, May 23, 2020. Recruitment began July 21, 2020, and is anticipated to be completed by October 30, 2020. TRIAL REGISTRATION: This clinical trial has been registered in the Iranian Registry of Clinical Trials (IRCT). The registration number is " IRCT20200506047323N1 ". Registration date is 23 May 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.