There is some indication that coronavirus disease 2019 (COVID-19) causes hypothalamic-pituitary-adrenal axis insufficiency. However, being on glucocorticoids makes it difficult to fully investigate this axis, especially in patients with severe COVID-19. We aimed to discover if there was a connection between blood total cortisol and adrenocorticotropic hormone (ACTH) levels and mortality in patients with COVID-19. In Iran, 154 hospitalized patients with COVID-19 were studied in a prospective cohort study. ACTH and cortisol levels in the blood were measured on the first or second day of hospitalization. Most patients (52.6 vs. 47.4%) were men over 50 years old (55.8%), and 44.4% had an underlying illness. Serum cortisol and plasma ACTH medians were 15.6 (μg/dl) and 11.4 (pg/ml), respectively. 9.09% of the patients died. Cortisol levels were substantially lower in those who died (11.3 μg/dl) than in patients who were discharged (16.7 μg/dl, P < 0.01 ), while ACTH levels were unaffected. The most important factors determining mortality, according to the logistic model, were blood cortisol levels, the existence of an underlying disease, and the use of a mechanical ventilator. Cortisol levels that rose by one-unit correlated with a 26% lower risk of mortality. Comorbidities and mechanical ventilation increased the risk of death by 260 and 92 times, respectively. It can be concluded that in patients with COVID-19, a low cortisol level is linked to a high risk of mortality. Patients may sometimes have relative primary adrenal insufficiency. To judge and decide on therapeutic interventions, more reliable and long-term follow-up studies are required.

Objectives This study aims to investigate the effect of Famotidine on the recovery process of COVID-19 patients. Trial design This phase III randomized clinical trial was designed with two parallel arms, placebo-controlled, single-blind, and concealed allocation. Participants All COVID-19 patients admitted to Shahid Mohammadi Hospital in Bandar Abbas whose PCR test results are positive for SARS-Cov-2 and sign the written consent of the study are included in the study and immunocompromised patients, end-stage renal disease, moderate renal failure (clearance Creatinine 30 to 50 ml/min) or stage 4 severe chronic kidney disease or need for dialysis (creatinine clearance lesser than 30 ml/min), history of liver disease, hepatitis C infection or alcoholism, Glucose 6 phosphate dehydrogenase deficiency(G6PD), the ratio of Alanine transaminase to Aspartate transaminase 5 times above the normal limit, history or evidence of long QT segment on Electrocardiogram, psoriasis or porphyria, pregnancy, use of oral contraceptives, Dasatinib, Neratinib, Ozanimod, Pazopanib, Rilpivirine, Siponimod and/or Tizanidine and allergies to any study drug are excluded. Intervention and comparator Intervention group receives standard pharmacotherapy according to the treatment protocols of the National Committee of COVID-19 and oral famotidine 160 mg (Manufactured by Chemidarou Pharmaceutical Company) four times a day until the day of discharge, for a maximum of fourteen days. Comparator group receives standard drug therapy according to the treatment protocols of the National Committee of COVID-19 and placebo in the same dosage. Main outcomes Patients’ temperature, respiration rate, oxygen saturation, lung infiltration, lactate dehydrogenase and complete blood count were measured at the baseline (before the intervention) and on day 14 after the intervention or on the discharge day. Randomisation The person who has no role in admitting patients and assigning patients to random codes preparing random sequences using online tools and by permuted block randomization method. Eligibility criteria are monitored by the person responsible for admitting patients. Codes in a random sequence are assigned to patients by the treatment team without knowing that each code is in the intervention or comparator group. Patient codes are then matched to randomly generated sequence information for interventions. Blinding (masking) All participants are unaware of which group of this study they are in and after grouping patients in the groups, Patients receive Famotidine in the treatment group and receive a placebo in the control group. The lead researcher, care givers, data collectors, and outcome assessors are aware of the grouping of patients. Numbers to be randomised (sample size) As there is no prior work on this research question, so no assumptions for the sample size calculation could be made. A total of 20 patients participate in this study, which are randomly divided into two groups of 10 as intervention or control groups. Trial status Version 3 of the protocol was approved by the Deputy of Research and Technology and the ethics committee of Hormozgan University of Medical Sciences on August 2, 2020, with the local code 990245, and the recruitment started on August 17, 2020. recruitment ended on August 31, 2020. Since the recruitment ended earlier than expected (the expected recruitment end date was 21/12/2020), we submitted post recruitment but prior to publication of the results. Trial registration The protocol was registered before starting subject recruitment under the title: The effect of Famotidine on the improvement of patients with COVID-19, IRCT20200509047364N2, at Iranian Registry of clinical trials (https://www.irct.ir/trial/49657) on 17 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 dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Background: No specific study has investigated the effect of non-steroidal anti inflammatory drugs (NSAIDs) and especially the effects of Ibuprofen on COVID-19, so far. Objectives: The purpose of this study was to investigate the effect of Ibuprofen on the severity of COVID-19 and mortality caused by the disease. Methods: This study was conducted on 158 patients with COVID-19 who had consumed Ibuprofen, Gelofen, and Novafen for at least one week in the last three months. Patients were divided into three groups (mild, moderate and sever). The relationship among the severity of the disease and the history of ibuprofen consumption, diabetes, history of cardiovascular problems, hypertension, and GFR was investigated. Also, the association between the history of ibuprofen consumption, GFR ≤ 60 mL/min, hypertension, LDH ≥ 500 U/L, lymphocyte count ≤ 1500, and mortality was examined. Results: Our findings showed a significant relationship between the history of Ibuprofen before COVID-19 and the severity of COVID-19, as well as the mortality rate (P value < 0.001, adjusted odd ratio: 2, respectively). This study also showed a significant relationship among the severity of the disease and the history of smoking, diabetes, hypertension, history of cardiovascular diseases, and GFR. In addition, a significant relationship was found among GFR ≤ 60 mL/min mortality, diabetes, LDH ≥ 500 U/L, and lymphocyte count ≤ 1500. Conclusions: Our study showed a significant relationship between the history of the consumption of ibuprofen and its compounds before COVID-19 and the severity of COVID-19, as well as the mortality rate of the patients with this disease, and accordingly, this result can suggest health policies during the epidemic of COVID-19.

Objectives Severe acute respiratory infection (SARI) caused by the SARS-CoV-2 virus may cause lung failure and the need for mechanical ventilation. Infection with SARS-COV-2 can lead to activation of inflammatory factors, increased reactive oxygen species, and cell damage. In addition to mucolytic effects, N-Acetylcysteine has antioxidant effects that we believe can help patients recover. In this study, we evaluate the efficacy of N-Acetylcysteine in patients with severe COVID-19. Trial design This is a prospective, randomized, single-blinded, phase 3 controlled clinical trial with two arms (ratio 1:1) parallel-group design of 40 patients, using the placebo in the control group. Participants All severe COVID-19 patients with at least one of the following five conditions: (respiration rate > 30 per minute), hypoxemia (O2 ≤ saturation, arterial oxygen partial pressure ratio <300), pulmonary infiltration (> 50% of lung area during 24 48 h), Lactate dehydrogenase (LDH) > 245 U / l, Progressive lymphopenia, and admitted to the intensive care unit of Shahid Mohammadi Hospital in Bandar Abbas and have positive PCR test results for SARS-Cov-2 and sign the written consent of the study will be included. Patients will be excluded from the study if they have a history of hypersensitivity to N-Acetylcysteine, pregnancy, or refuse to participate in the study. Intervention and comparator After randomization, participants in the intervention group receive standard of care (SOC) according to the National Committee of COVID-19 plus N-acetylcysteine (EXI-NACE 200mg/mL, in 10mL ampules of saline for parenteral injection (EXIR pharmaceutical company)) at a dose of 300 mg/kg equivalent to 20 gr as a slow single intravenous injection on the first day of hospitalization. In the control group patients receive SOC and placebo ( Sterile water for injection as the same dose). The placebo is identical in appearance to the N-acetylcysteine injection (EXIR pharmaceutical company as well). Main outcomes The primary endpoint for this study is a composite endpoint for the length of hospitalization in the intensive care unit and the patient's clinical condition. These outcomes were measured at the baseline (before the intervention) and on the 14th day after the intervention or on the discharge day. Randomisation Eligible participants (40) will be randomized in two arms in the ratio of 1: 1 (20 per arm) using online web-based tools and by permuted block randomization method. To ensure randomization concealment, random sequence codes are assigned to patients by the treatment team at the time of admission without knowing that each code is in the intervention or comparator group. Blinding (masking) All participants will be informed about participating in the study and the possible side effects of medication and placebo. Patients participating in the study will not be aware of the assignment to the intervention or control group. The principal investigator, health care personnel, data collectors, and those evaluating the outcome are aware of patient grouping. Numbers to be randomised (sample size) A total of 40 patients participate in this study, which are randomly divided; 20 patients in the intervention group will receive SOC and N-acetylcysteine, 20 patients in the control group will receive SOC and placebo. Trial status First version of the protocol was approved by the Deputy of Research and Technology and the ethics committee of Hormozgan University of Medical Sciences on February 14, 2021, with the local code 990573, and the recruitment started on March 2, 2021 and the expected recruitment end date is April 1, 2021. Trial registration The protocol was registered before starting participant recruitment entitled: Evaluation of the efficacy of N-Acetylcysteine in severe COVID-19 patients: a randomized controlled phase III clinical trial, IRCT20200509047364N3, at Iranian Registry of clinical trials on 20 February 2021. 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. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Background Potential dietary inflammation can precursor chronic diseases such as hepatic disorders. We aimed to examine the association of empirical dietary inflammatory patterns (EDIP) and dietary inflammation scores (DIS) with the risk of nonalcoholic fatty liver diseases (NAFLD) in Iranian adults. Methods This case–control study was conducted on 225 newly diagnosed NAFLD cases and 450 controls aged 20–60 years. The individuals’ dietary data were collected using a validated food frequency questionnaire. The detection of NAFLD in subjects was done using the ultrasonography scan of the liver and confirmation of gastroenterologists. To calculate of EDIP score, the average daily intakes of each item (15 food items) were multiplied by the proposed weights, and then all the weighted values were summed. Also, to calculate the DIS score, each food item (18 food items) is multiplied by its specific weight to obtain the weighted values of each item. The weighted values were then standardized using the Z-score. Finally, the standardized weighted values of all the items were summed to get the overall DIS score for the individuals. Logistic regression models, adjusted for potential confounders, were used to estimate the odds ratios and 95% confidence interval (CI) of NAFLD across tertiles of EDIP and DIS. Results The mean (SD) age and BMI of the study population (53% male) were 38.1 (8.8) years and 26.8 (4.3) kg/m2, respectively. The median (IQR) of EDIP and DIS scores in individuals were 0.52 (0.34, 0.73), and 0.04 (− 0.55, 0.59), respectively. Based on the multivariable-adjusted model, after controlling for age, sex, physical activity, smoking, marital status, waist-to-hip ratio, and dietary energy intake, individuals in the second (OR 2.01, 95% CI 1.07–3.76) and third tertiles of DIS (OR 2.54, 95% CI 1.39–4.63) had a higher odds of NAFLD compared to the lowest tertile of DIS (Ptrend = 0.003). Also, in the final model, there is a significant direct association between EDIP score and odds of NAFLD [(OR T2 vs. T1 = 0.88, 95% CI 0.50–1.57) and (OR T3 vs. T1 = 1.82, 95% CI 1.02–3.23)], (Ptrend = 0.031). Conclusion Our results suggested that higher scores of EDIP and DIS, indicating the high inflammatory potential of dietary pattern, are associated with increased odds of NAFLD in Iranian adults.

Objective: Diabetes mellitus is a chronic illness and adherence to medications is vital to manage the illness. The purpose of this study was to examine the prediction of medication adherence based on personality factors in a group of individuals with type 2 diabetes in Yasuj. Materials and Methods: One hundred twenty individuals with type 2 diabetes who visited health centers were selected for this study through convenience sampling. The participants completed the NEO-Five Factor Inventory and Medication Adherence Rating Scale (MARS). The data were analyzed by mean, standard deviation, and multiple regression analysis using SPSS software. Results: The results showed that among the big-five personality factors, only neuroticisms significantly predicted adherence to medications (β= -0.31, P-value< 0.003). Furthermore, the model explained only 19% of the variance in medication adherence (R2= 0.19, P-value< 0.01). Conclusion: This study indicated that a large proportion of patients with type 2 diabetes did not adhere to their medications. This study highlighted that the personality trait of neuroticism was important in predicting medication adherence in patients with type 2 diabetes.

Background/AimThis study aimed to examine the associations between dietary protein score and carbohydrate quality index (CQI) and the risk of chronic kidney disease (CKD) in Iranian adults.MethodsThis population-based cohort study was performed within the Tehran Lipid and Glucose Study framework on 6,044 subjects aged ≥18 years old, who were followed up for a mean of 7.7 years. Dietary protein score and CQI were determined using a food frequency questionnaire. CKD was defined as an estimated glomerular filtration rate &lt;60 ml/min/1.73 m2. A multivariate Cox proportional hazard regression model was used to estimate the risk of CKD across tertiles of protein score and CQI.ResultsThe mean (standard deviation) of age and body mass index of participants were 37.9 (12.8) years and 26.8 (4.7) kg/m2, respectively. During the 7.7 ± 2.7 years of follow-up, 1,216 cases (20.1%) of CKD were ascertained. In the final adjusted model, individuals in the highest tertile of protein score had decreased risk of CKD (HR: 0.85, 95% CI: 0.74–0.98, Ptrend = 0.033). Also, there is a significant association between total carbohydrate score (HR: 0.85, 95% CI: 0.73–0.99, Ptrend = 0.016), the ratio of whole grain/total grains (HR: 0.81, 95% CI: 0.70–0.94, Ptrend = 0.004), and glycemic index (HR: 1.30, 95% CI: 1.12–1.51, Ptrend &lt; 0.001) and risk of CKD. However, no significant association was found between total protein intakes, plant-to-animal ratio, and solid carbohydrate/total carbohydrate with the risk of CKD.ConclusionOur results revealed a diet with a high protein score and high quality of carbohydrates, characterized by higher intakes of plant proteins, low glycaemic index (GI) carbohydrates, whole grain, fibers, and lower intakes of animal proteins, can be related to reduced CKD risk.

Introduction: This study aimed to examine the relationship between liver enzymes and severity of COVID-19. Furthermore, patients with clinical diagnosis (PCR negative) and patients with definitive laboratory diagnosis (PCR positive) of COVID-19 were compared in terms of disease severity. Method: This cross-sectional study enrolled 158 patients with COVID-19 admitted based on chest CT scan findings to the COVID-19 ward of Shahid Mohammadi Hospital, affiliated with Hormozgan University of Medical Sciences (Iran).Reversetranscriptase polymerase chain reaction (RT-PCR) test was performed for all the patients, who were accordingly divided into groups of PCR negative COVID-19 with clinical diagnosis, and COVID-19 with definitive laboratory diagnosis. Results: The results indicated a significant elevation of AST (Aspartate transaminase) and Alanine transaminase (ALT) in the PCR positive group compared to the PCR negative group (p = 0.02, p = 0.04, respectively). The results also showed a correlation between AST level and COVID-19 severity (p < 0.01, OR = 2.06). Moreover, a significant correlation was observed between ESR and the levels of AST and ALT (r = 0.24 for AST, r = 0.47 for ALT). Conclusion: AST and ALT significantly increased in the PCR positive group compared to the PCR negative group, and AST was correlated with COVID-19 severity. Furthermore, a significant correlation was observed between ESR and the levels of AST and ALT. Therefore, COVID-19 involves liver both directly and through the inflammatory system.