Delay in Regular Visits of Chronic Disease Patients and Its Associated Factors during the COVID-19 Pandemic.

Background: Chronic patients need regular follow-ups. During the COVID-19 pandemic, these regular visits can be affected. The delay of chronic patients and its contributing factors in their periodic visits during the COVID-19 pandemic are examined here. Methods: This cross-sectional study was conducted between February and June 2021, in Fars, Iran. Two hundred and eighty-six households with at least one chronic patient were recruited. Then, several trained questioners called the studied households and asked about the studied variables. The dependent variable was the number of delays in regular visits during the COVID-19 pandemic. The results were analyzed through Poisson regression by SPSS Statistics version 22 and GraphPad Prism software version 9. A significance level of 0.05 was considered for this study. Results: Out of 286 households 113 (73.4%) fathers, 138 (70.1%) mothers, and 17 (58.6%) children in the households reported delayed referral. In fathers, referring to the health center was significantly associated with a decrease in the number of delays (P=0.033). The higher age of the householder (P=0.005), the higher number of children (P=0.043), and having a family physician (P=0.007) in the mothers' group, also the number of children in households (P=0.001) in the children group were significantly associated with increasing the number of delays. Conclusion: COVID-19 pandemic not only creates direct harmful effects but also adversely affects people in danger of chronic diseases. Delays in follow-ups are taken into account as a major challenge during the COVID-19 pandemic. This issue is not limited to rural or urban residency.

Analyzing delay in referral of pregnant women and children under five years old during the COVID-19 pandemic: Fars Province, Iran.

The researchers assessed the delay in referral of pregnant women and children under five years old during the COVID-19 pandemic that they require regular healthcare. This cross-sectional study was conducted in 2021 in Fars, Iran. A total of 591 households with pregnant women and children under five years old were recruited, then having delay and the number of their delays in regular visits during the COVID-19 outbreak was asked. A total of 153 children under five years old (51.7%) and 93 pregnant women (31.5%) reported delays in referral. In children, higher age and referral to the family physician and private clinic, and in pregnant women, higher gestational age and pregnancy rank and having health problems (e.g., preeclampsia in the current pregnancy) significantly enhanced the number of delays. Due to the vulnerability of these groups, it is necessary to consider active care for them as a priority at the primary care level.

Evaluation of the efficacy and safety of recombinant erythropoietin on the improvement of hospitalised COVID-19 patients: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: To evaluate the effect of recombinant erythropoietin on hospitalised COVID-19 patients. TRIAL DESIGN: Concealed, randomized, single-blinded, phase 2 controlled clinical trial with two arm parallel-group design of 20 patients allocated with 1:1 ratio and using the placebo in the control group. PARTICIPANTS: This study will be performed at Shahid Mohammadi Hospital in Bandar Abbas, Hormozgan in Iran. All positive (PCR confirmed) COVID-19 patients ≤65 years old who have Hb≤9 and at least one of the severe COVID-19 symptoms (tachypnea (breathing rate> 30 beats per minute), hypoxemia (O2 ≤93 saturation, the partial pressure ratio of arterial oxygen <300), Lung infiltration (> 50% of lung field within 24 to 48 hours), progressive lymphopenia, LDH>245 U/I, CRP>100) and are willing to cooperate in this project will be included in the study. Patients with a history of coronary heart disease, thrombosis, deep vein thrombosis, chronic lung disease, diabetes mellitus, weakened immune system, end-stage renal disease, liver disease, and patients with a history of taking oral contraceptive pills, systolic blood pressure more than 160 mm Hg, diastolic blood pressure more than 90 mm Hg and age over 65 and erythropoietin above 500 are excluded. INTERVENTION AND COMPARATOR: Patients will receive the standard of care (SOC) based on the treatment protocols of the Iranian National Committee of COVID-19 and recombinant erythropoietin (EPREX Manufactured by Johnson and Johnson Pharmaceutical Company) 300 units / Kg or 4000IU as subcutaneous (SQ) injection three times a day for 5 days and simultaneously Enoxaparin 1 mg/kg SQ daily is also taken to prevent thrombosis in the intervention group. Patients' blood pressure, along with other vital signs, are checked regularly and at regular intervals. In the control group, patients received SOC and the placebo (distilled water) is given as a subcutaneous injection three times a day for 5 days. We use sterile water for injection (EXIRpharmaceutical company) as the placebo. To the same appearance of the placebo and the recombinant erythropoietin, they are taken in a separate room in the same size syringes and cover with labels before injection. MAIN OUTCOMES: The main outcome for this study is a composite endpoint for Patient clinical symptoms (Respiratory rate, Oxygen saturation state and arterial oxygen partial pressure ratio, Lung infiltration status, blood pressure), Laboratory tests (LDH, CRP, Lymphocyte count, Endogenous erythropoietin, and Haemoglobin level). All of these will be assessed at the beginning of the study (before the intervention) and day 5 after the intervention. The study will also evaluate side effects and how to manage them. RANDOMISATION: Eligible participants (20) will be randomized in two arms in the ratio of 1: 1 (10 per arm) by permuted block randomization method using online web-based tools. BLINDING (MASKING): 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 20 patients will participate in this study, who are randomly allocated to the 2 arms with a 1:1 ratio; 10 patients in the intervention group will receive SOC and recombinant erythropoietin, and 10 patients in the control group will receive SOC and placebo. TRIAL STATUS: The protocol version is 3.0, approved by the Deputy of Research and Technology and the ethics committee of Hormozgan University of Medical Sciences on 6th June 2020, with the local grant number of 990108. The expected recruitment end date was on 21th December 2020 but since we had a wide and careful exclusion criteria because of the adverse reactions of the medication, the recruitment (for both cases and controls) was not so easy and did not finish on the expected date and we are still recruiting now. Recruitment began on 17th August 2020 and the updated expected recruitment end date is 1st August 2021. TRIAL REGISTRATION: The protocol was registered before starting subject recruitment under the title: Evaluation of the effect of recombinant erythropoietin on the improvement of COVID-19 patients, IRCT20200509047364N1, at Iranian Registry of clinical trials ( https://en.irct.ir/trial/49282 ) on 2020/08/09. 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).

The Roles of Vitamin D in Increasing the Body's Immunity and Reducing Injuries due to Viral Infections: With an Emphasis on its Possible Role in SARS-CoV-2 (COVID-19).

BACKGROUND: It is known that vitamin D can increase the body's immunity against some viral infections. Many people worldwide have vitamin D deficiency; therefore, this has become a public concern whether vitamin D is an important factor protecting against COVID-19 infection. In this paper, the data about the roles of vitamin D in immunity and recovery from viral infections, especially novel Coronavirus disease (COVID- 19), are reviewed. METHODS: The electronic databases of Pubmed, Google Scholar, Research Gate, Excerpta Media Database (EMBASE), and Medical and Health Education (Medrix) were searched. RESULTS: Vitamin D is considered an important factor in immune homeostasis. Various effects have been considered for this nutrient on the immune system, particularly because of vitamin D receptor (VDR) and Cytochrome P450 Family 27 Subfamily B Member 1 (CYP27B1) expression in most of the immune cells. Vitamin D can increase cellular immunity, reduce cytokine storm, and enhance antioxidants production. It also has modulatory effects on Angiotensin-converting enzyme 2 (ACE2) receptors and might have protective functions against acute lung injuries, including COVID-19 infection. However, there are some articles against this positive effect. CONCLUSION: Vitamin D supplementation is reported to be effective in the enhancement of the immune system and might be effective in the treatment and prevention of COVID-19 infection, especially in those with its deficiency. However, it should be considered that vitamin D deficiency shows the overall health status of the patients and cannot be considered specific for COVID-19 infection.

The efficacy of N-Acetylcysteine in severe COVID-19 patients: A structured summary of a study protocol for a randomised controlled trial.

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).

The Efficacy of Famotidine in improvement of outcomes in Hospitalized COVID-19 Patients: A structured summary of a study protocol for a randomised controlled trial.

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).