Effects of Melatonin and Propolis Supplementation on Inflammation, Oxidative Stress, and Clinical Outcomes in Patients with Primary Pneumosepsis: A Randomized Controlled Clinical Trial.

BACKGROUND AND OBJECTIVE: The present study aimed to investigate the effects of propolis and melatonin supplementation on inflammation, clinical outcomes, and oxidative stress markers in patients with primary pneumosepsis. MATERIALS AND METHODS: This pilot randomized controlled trial was conducted on 55 patients with primary pneumosepsis who were randomly assigned to the intervention and control groups. In the three intervention groups, the patients received propolis alone (1,000 mg/day), propolis (1,000 mg/day) plus melatonin (20 mg/day), and melatonin alone (20 mg/day). The control group received placebo. The inflammatory and oxidative stress markers as well as clinical outcomes were evaluated before and after the intervention, and the 28-day survival rate was also recorded. RESULTS: After the intervention, the combination of propolis and melatonin significantly reduced interleukin-6 (-55.282 pg/mL) and C-reactive protein (-21.656 mg/L) levels, while increasing gavage intake (326.680 mL/day) and improving some clinical outcomes (APACHE II, SOFA, and NUTRIC scores) compared to the control group. However, no significant difference was observed between the groups in terms of oxidative stress and hematological indices. In addition, there was no significant difference in the 28-day survival rate between the groups (p = 0.07). CONCLUSION: Supplementation with propolis and melatonin may improve clinical outcomes by reducing inflammation. Further investigations are required to confirm these findings.

Methylene blue for treatment of hospitalized Covid-19 patients: a randomized, controlled, open-label clinical trial, phase 2

ABSTRACT Background: There is no pharmacological intervention on the treatment of hypoxemia and respiratory distress in COVID-19 patients. Objective: The objective of the study was to study the effect of the reduced form of methylene blue (MB) on the improvement of oxygen saturation (SpO2) and respiratory rate (RR). Methods: In an academic medical center, 80 hospitalized patients with severe COVID-19 were randomly assigned to receive either oral MB along with standard of care (SOC) (MB group, n = 40) or SOC only (SOC group, n=40). The primary outcomes were SpO2 and RR on the 3rd and 5th days. The secondary outcomes were hospital stay and mortality within 28 days. Results: In the MB group, a significant improvement in SpO2 and RR was observed on the 3rd day (for both, p < 0.0001) and also the 5th day (for both, p < 0.0001). In the SOC group, there was no significant improvement in SpO2 (p = 0.24) and RR (p = 0.20) on the 3rd day, although there was a significant improvement of SpO2 (p = 0.002) and RR (p = 0.01) on the 5th day. In the MB group in comparison to the SOC group, the rate ratio of increased SpO2 was 13.5 and 2.1 times on the 3rd and 5th days, respectively. In the MB group compared with the SOC group, the rate ratio of RR improvement was 10.1 and 3.7 times on the 3rd and 5th days, respectively. The hospital stay was significantly shortened in the MB group (p = 0.004), and the mortality was 12.5% and 22.5% in the MB and SOC groups, respectively. Conclusions: The addition of MB to the treatment protocols significantly improved SpO2 and respiratory distress in COVID-19 patients, which resulted in decreased hospital stay and mortality. ClinicalTrials.gov: NCT04370288

METHYLENE BLUE FOR TREATMENT OF HOSPITALIZED COVID-19 PATIENTS: A RANDOMIZED, CONTROLLED, OPEN-LABEL CLINICAL TRIAL, PHASE 2.

BACKGROUND: There is no pharmacological intervention on the treatment of hypoxemia and respiratory distress in COVID-19 patients. OBJECTIVE: The objective of the study was to study the effect of the reduced form of methylene blue (MB) on the improvement of oxygen saturation (SpO2) and respiratory rate (RR). METHODS: In an academic medical center, 80 hospitalized patients with severe COVID-19 were randomly assigned to receive either oral MB along with standard of care (SOC) (MB group, n = 40) or SOC only (SOC group, n=40). The primary outcomes were SpO2 and RR on the 3rd and 5th days. The secondary outcomes were hospital stay and mortality within 28 days. RESULTS: In the MB group, a significant improvement in SpO2 and RR was observed on the 3rd day (for both, p < 0.0001) and also the 5th day (for both, p < 0.0001). In the SOC group, there was no significant improvement in SpO2 (p = 0.24) and RR (p = 0.20) on the 3rd day, although there was a significant improvement of SpO2 (p = 0.002) and RR (p = 0.01) on the 5th day. In the MB group in comparison to the SOC group, the rate ratio of increased SpO2 was 13.5 and 2.1 times on the 3rd and 5th days, respectively. In the MB group compared with the SOC group, the rate ratio of RR improvement was 10.1 and 3.7 times on the 3rd and 5th days, respectively. The hospital stay was significantly shortened in the MB group (p = 0.004), and the mortality was 12.5% and 22.5% in the MB and SOC groups, respectively. CONCLUSIONS: The addition of MB to the treatment protocols significantly improved SpO2 and respiratory distress in COVID-19 patients, which resulted in decreased hospital stay and mortality. ClinicalTrials.gov: NCT04370288.

Comparison of "cough peak expiratory flow measurement" and "cough strength measurement using the white card test" in extubation success: A randomized controlled trial.

BACKGROUND: Failed extubation and subsequent re-intubation in ventilated patients can lead to many adverse consequences, including organizational and personal expenditures. Extubation decisions based on subjective methods are a major contributor to extubation failure. This study compared the effect of cough peak expiratory flow (PEF) measurement and cough strength measurement using the white card test (WCT) on extubation success. MATERIALS AND METHODS: This randomized clinical trial was conducted in two groups in 2018 on 88 ventilated patients in intensive care units of Imam Reza Hospital in Mashhad, Iran. Ninety patients were divided into two groups of 45, but two were excluded from the white card group. The criteria established for extubation included PEF ≥60 L/min during coughing in the cough PEF group and noticing card humidity in the WCT group. In both groups, extubation success was determined as the sole outcome and was compared with the standard PEF and cough strength. The researcher who assessed the outcome and statistician were blinded about group allocation. RESULTS: Extubation success was measured as 97.8% in the cough PEF group and 76.7% in the WCT group (P = 0.003) during the first 24 h. In the second 24 h, however, successful extubation was reported as 90.9% in the cough PEF group and 60.6% in the WCT group (P = 0.002). CONCLUSION: Using the cough PEF rate increases the likelihood of extubation success and reduces adverse effects, and is recommended to be used for extubation decision-making.

The Application of a Reduced Dye Used in Orthopedics as a Novel Treatment against Coronavirus (COVID-19): A Suggested Therapeutic Protocol.

The severe acute respiratory syndrome caused by COVID-19 is now a global catastrophic event. Currently there is no approved drug or vaccine for the disease. Methylene blue (MB, oxidized form, blue color) has been used in many different areas of clinical medicine, ranging from malaria to orthopedics. Leucomethylene Blue (reduced form of MB, colorless) may be applied for the treatment of COVID-19 according to the scientific evidences. In severe patients, there is a cytokine storm (hyperinflammation) and high oxidative stress (OS). Inflammation and OS has a mutual correlation and exacerbate each other. In human body, MB first induces OS through absorbing electron (like a free radical) from other molecules, if the body could counteract to this OS, then reduced MB decreases OS through other mechanisms. Reduced MB could prevent inflammation, propagation of the virus RNA, and also improves hypoxia through reducing methemoglobin. Therefore, to avoid the increment of OS, we suggest using Leucomethylene Blue through the following protocol: The IV cocktail contains 50 mg MB (1mg/kg, 50-kg weight), 1000-2000 mg vitamin C, 500-1000 mg N-Acetylcysteine (or glutathione or cysteine or α-lipoic acid) and 10-20 gr urea (optional) in 100 ml dextrose 5%. Before the injection, the cocktail should be kept in a dark place for 1-2 hour to become fade or colorless.

Implementation of a flexible visiting policy in intensive care unit: A randomized clinical trial.

BACKGROUND: Visitation is one of the most critical needs of patients in intensive care units (ICUs). Clinicians should enable a more flexible visitation policy to prevent the adverse effects of a restricted approach. AIM AND OBJECTIVES: This study aimed at investigating the relationship between increasing visitation time and patients' physiological parameters in intensive units. Additionally, nurses' beliefs and attitudes towards visiting is examined in this research. DESIGN: Parallel randomized clinical trial. METHODS: This study was conducted in four general medical ICUs in Iran. In total, 60 patients and 57 nurses participated in this study. The patients' physiological parameters were measured at particular times in both groups. Moreover, the nurses responded to the questionnaire on beliefs and attitudes towards visitation in intensive units before and after the intervention. RESULTS: Among all the physiological parameters, systolic and diastolic blood pressure and heart rate had a significant decrease within the normal range 10 and 30 minutes after visiting in the intervention group (P < .05), and nurses' beliefs and attitudes score were at the middle of the survey scoring range (0-120). However, no significant difference was found between nurses' belief and attitude score and intervention in any groups (P > .05). CONCLUSION: The findings indicate that increasing visitation times can lead to a positive effect on the stability and balance of patients' physiological parameters. RELEVANCE TO CLINICAL PRACTICE: A more flexible visiting policy can provide a therapeutic environment where not only patients' physiological disorders are minimised as much as possible but also a higher level of patients' health and satisfaction are reached.

Effects of propolis and melatonin on oxidative stress, inflammation, and clinical status in patients with primary sepsis: Study protocol and review on previous studies.

BACKGROUND: Previous studies have explored the anti-inflammatory, anti-infection and oxidative stress reduction effects of propolis and melatonin in experimental studies. However, there are no studies at present exploring the effects of propolis and melatonin in patients with primary sepsis. The present study aims to evaluate the potential effects of propolis and melatonin as a pharmaceutical agent in patients with primary sepsis. METHODS/DESIGN: The study will be conducted as a randomized controlled clinical trial at the Imamreza hospital. Patients with primary sepsis, in four equal groups, will be recruited for the study. The treatment drugs are propolis and melatonin and the placebo. The following primary and secondary outcome measures will be evaluated: APACHE II Score, SOFA score, NUTRIC score, inflammatory factors, and oxidative stress markers. DISCUSSION: We describe the protocol for a clinical trial design evaluating the effects of simultaneous administration of propolis and melatonin in patients with primary sepsis. The result of the present study, positive or negative, should provide a step change in the evidence guiding current and future policies regarding the use of propolis and melatonin as an auxiliary treatment in patients with primary sepsis. TRIAL REGISTRATION: Iranian Registry of Clinical Trials: IRCT20181025041460N1. Registered on 6 November 2018.

The Provision of Palliative Care for Noncancer Patients With Advanced Disease: Equity Does Matter.

According to the World Health Organization, the main mission of palliative care is to optimize the quality of life of patients with serious chronic disease, as well as their caregivers, by providing biopsychosociospiritual care. However, historically, the primary focus of palliative care is on providing care only for cancer diseases. Based on the current literature, it is assumed that palliative care is not provided for many chronic diseases on a regular basis and in many cases, a clinical guideline does not exist for providing palliative care.

Using Intra-Aortic Balloon Pump for Management of Cardiogenic Shock Following Aluminum Phosphide Poisoning; Report of 3 Cases.

INTRODUCTION: Aluminium phosphide (Alp) poisoning mortality rate has been reported as high as 70-100%, and refractory hypotension and cardiogenic shock are the two most common presentations leading to death. Due to lack of specific antidote, all treatments are focused on supportive care and recently, intra-aortic balloon pump (IABP) has been suggested to treat cardiogenic shock resulting from toxic myocarditis. In the current paper, we introduce three Alp poisoned patients for whom IABP was applied to manage their refractory shock. CASE PRESENTATION: Two men and one woman who were admitted to emergency department (ED) of Imam Reza academic Hospital, Mashhad, Iran due to intentional Alp poisoning are reported. The cases visited the ED shortly after ingestion and nearly all of them showed hypotension, tachycardia and metabolic acidosis during early hospitalization. Due to persistent shock state, despite receiving intravenous fluid therapy and vasopressor agents, IABP insertion was performed in these cases. Finally, one of them survived and the other two died. CONCLUSION: It still cannot be decided whether IABP insertion is effective in cases of Alp poisoning or not. It might be reasonable to try this intervention along with other conservative treatments in patients who survive more than 12 hours and consistently suffer from refractory hypotension.