Evaluating the factors affecting clinical outcomes in critically ill COVID-19 unvaccinated patients admitted to the intensive care unit in a lower-middle-income country.

Background: COVID-19, the most destructive pandemic of this century, caused the highest mortality rate among ICU patients. The evaluation of these patients is insufficient in lower-middle-income countries with limited resources during pandemics. As a result, our primary goal was to examine the characteristics of patients at baseline as well as their survival outcomes, and propose mortality predictors for identifying and managing the most vulnerable patients more effectively and quickly. Methods: A prospective analysis of COVID-19 ICU-admitted patients was conducted in our healthcare centre in Iran, from 1 April until 20 May 2020. Ninety-three patients were included in the study, and all were unvaccinated. A multi-variate logistic regression was conducted to evaluate mortality-associated factors. Results: There were 53 non-survivors among our ICU-admitted patients. The mean duration from symptoms' onset to hospitalization was 6.92 ± 4.27 days, and from hospitalization to ICU admission was 2.52 ± 3.61 days. The average hospital stay for patients was 13.23 ± 10.43 days, with 8.84 ± 7.53 days in the ICU. Non-survivors were significantly older, had significantly lower haemoglobin levels and higher creatine phosphokinase levels compared to survivors. They had marginally lower SpO2 levels at admission, higher vasopressor administrations, and were intubated more significantly during their ICU stay. The use of immunosuppressive drugs was also significantly higher in non-survivors. Logistic regression revealed that a one-point increase in APACHE II score at ICU admission increased mortality by 6%, and the presence of underlying diseases increased mortality by 4.27 times. Conclusion: The authors presented clinical mortality prediction factors for critically ill patients infected with COVID-19. Additional studies are necessary to identify more generalized mortality indicators for these patients in lower-middle-income countries.

The effects of colchicine on hospitalized COVID-19 patients: A randomized, double-blind, placebo-controlled clinical trial.

This study was designed to evaluate the effects of colchicine in the improvement of clinical outcomes of hospitalized COVID-19 patients. This prospective, randomized, double-blind, placebo-controlled clinical trial was conducted on adult patients (>18 years) with severe COVID-19. The included patients were randomly (1:1) assigned to the colchicine (2 mg loading dose followed by 0.5 mg twice daily for 7 days) or placebo group. Both groups received remdesivir and interferon beta-1b. The primary outcome of the study was to receive clinical response as ordinal scale of 1 or 2. Secondary outcomes were hospital complications and 28-day mortality. Between February and May 2021, 110 patients were included and 106 of them were analyzed. Baseline clinical characteristics and demographics were not significantly different. According to the ordinal scale, 30 patients in the control group (58.8%) responded to treatment within 7 days, while 35 patients (63.6%) in the colchicine group showed the same response (p = 0.61, odds ratio (OR) = 1.23, 95% CI [0.560-2.68]). On the 14th day, 87.3% of the colchicine group (n = 48) and 82.4% of the control group (n = 42) responded (p = 0.48, OR = 1.47, 95% CI [0.50.3-4.29]. In addition, 28-day mortality, intensive care unit admission, and hospital duration were not different between the groups (p = 0.99, 0.59, 0.06). Diarrhea and nausea were the major side effects dominant in the colchicine group. Colchicine showed no beneficial effects on clinical improvement and hospital complications in patients with COVID-19. Moreover, in case of prescription, the safety concerns of colchicine, specially gastrointestinal side effects, should be taken into account.

Melatonin as adjunctive therapy in patients admitted to the Covid-19.

Objective: Coronavirus has disrupted the natural order of the world since September 2019 with no specific medication. The beneficial effects of melatonin on sepsis and viral influenza were demonstrated previously, but its effects on covid-19, especially COVID -19 ICU, is unclear. Therefore, our aim was to determine the effects of melatonin in COVID-19 ICU patients. Methods: This is a retrospective cohort study in which the records of patients admitted to COVID -19 ICU of (XXX) during March to June 2020 were reviewed. According to inclusion criteria, patients who received 15 mg of melatonin daily were called MRG and the rest were called NMRG. Results: Thirty-one patients were included and analyzed, of which twelve patients were in MRG. Demographic and clinical characteristics, and laboratory data were similar between two groups at ICU admission. Melatonin had no significant effect on ICU duration, CRP and ESR, also the trend of changes was in favor of melatonin. Nevertheless, melatonin significantly reduced the NLR (OR = -9.81, p = 0.003), and also declined mortality marginally (p = 0.09). Melatonin was well tolerated with no major adverse effects, moreover the thrombocytopenia occurrence was significantly lower in MRG (p = 0.005). In MRG, survival increased and mortality risk decreased, although the difference between groups wasn't significant (p = 0.37), which might be related to the small sample-size. Conclusion: Our study showed that melatonin is unlikely to reduce mortality among COVID19 patients and with no significant effect on disease-specific biochemical parameters.

Effect of melatonin on stress-induced hyperglycemia and insulin resistance in critically-ill patients: A randomized double-blind, placebo-controlled clinical trial.

BACKGROUND: Hyperglycemia is a common finding which is associated with increased mortality and morbidity among critically ill patients. There is currently no evidence that melatonin could improve stress induced hyperglycemia (SIH). In this study, we evaluated the effect of melatonin on blood sugar and insulin resistance (IR) in critically-ill patients. METHODS: 104 critically-ill patients with SIH divided into two groups, receiving melatonin (6 mg BD for 3 days) or placebo. Changes of blood sugar, IR indices including homeostasis model assessment for insulin resistance and homeostasis model assessment adiponectin (HOMA-AD) ratios, Glasgow coma scale (GCS) were evaluated on the 4th day of melatonin prescription. On the 7Th day of study, changes of ventilator dependency and delirium were considered. Mortality and intensive care unit (ICU) stay were also compared between groups. RESULTS: On day 4, patients in the melatonin group had significantly lower blood glucose and HMOA-IR level compared with the placebo group (P=0.04 and P=0.03, respectively) whereas HOMA-AD level did not differ significantly from placebo group (p>0.2). Also, we did not observe any significant difference in GCS level at this time between groups (p>0.2). On day 7, melatonin could not improve ventilator dependency and delirium significantly (p>0.2) and also could not reduce mortality and ICU stay in comparison with placebo (p>0.2, P=0.2, respectively). CONCLUSION: Melatonin supplementation showed positive effect on blood sugar and somehow insulin resistance whereas it could not improve ICU complications.

A Clinical Monitoring Program of COVID-19 Outpatients: A Prospective Cohort Study.

PURPOSE: Coronavirus disease 2019 (COVID-19) has been associated with a high rate of mortality and morbidity. While a high portion of COVID-19 patients have mild symptoms, a limited number of clinical trials have evaluated the clinical course of this large group of patients. This study was designed to investigate the demographics and clinical characteristics and comorbidity of nonhospitalized COVID-19 patients. METHODS: This prospective, observational cohort study was performed on nonhospitalized adult patients (≥18 years) with COVID-19. Pharmacotherapy service was responsible for patients' assessment for up to 1 month. Demographic characteristics, the onset of symptoms, severity, duration, laboratory data, and hospitalization rate were evaluated by a pharmacist-based monitoring program. RESULTS: From 323 patients who had been referred to the emergency department, 105 individuals were recruited between April 26 and August 2, 2020. Most of the patients were female (66.7%) with a mean age of 39.39 years (SD: ± 15.82). The mean time of the symptom onset was 5.6 days (SD: ±1.79). The majority of patients suffered from fatigue (78.1%), sore throat (67.6%), cough (60%), and myalgia (55.2%). C-reactive protein, white blood cell, lymphocyte, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and hemoglobin levels were recovered significantly during the first two weeks (P < 0.001). Hydroxychloroquine, naproxen, diphenhydramine, azithromycin, and vitamin D3 were the most common medications administered (98%, 96%, 94%, 68%, and 57%, respectively). Forty patients were not symptom-free after the one-month follow-up, and 8 patients (7.6%) were required to revisit without the need for hospitalization. Anosmia (18.1%) and fatigue (17.1%) were the most common persisted symptoms. There were no significant differences between symptom-free and symptomatic patients. CONCLUSION: Mild COVID-19 patients had a wide variety of symptoms and could be symptomatic even one month after the onset of symptoms. The pharmacist-based monitoring system can contribute beneficially to patients through the evaluation of symptoms, reduction of unnecessary visits, and provision of updated information to patients concerning the status of their illness.

A 3-armed randomized controlled trial of nurses' continuing education meetings on adverse drug reactions.

INTRODUCTION: Nurses' insufficient knowledge of adverse drug reactions is reported as a barrier to spontaneous reporting. Therefore, CE meetings could be utilized to enhance nurses' competencies. METHODS: In a 3-armed randomized controlled trial, 496 nurses, working in a tertiary medical center, were randomly allocated to a didactic lecture, brainstorming workshop, or the control group (delayed education). Similar instructors (2 clinical pharmacists) prepared and delivered the educational content to all 3 groups. Outcomes were declarative/procedural knowledge (primary outcome), participation rate, and satisfaction. Knowledge was evaluated using a validated researcher-made questionnaire in 3 time points: immediately before, immediately after, and 3 months after each session. Participants' satisfaction was assessed immediately after each meeting via a standard tool. Data were analyzed using appropriate parametric and nonparametric tests. RESULTS: Rate of participation was 37.7% for the lecture group and 47.5% for the workshop group. The workshop participants were significantly more satisfied in comparison with the lecture group (p < .05). Mean knowledge scores were similar at baseline in the 3 study groups (43-47). Immediately after the meeting, knowledge was significantly higher in the lecture group (79.1 ± 11.9 vs 73.7 ± 11.3; p = .01). At the follow-up, knowledge scores of the lecture and workshop groups were similar, while significantly higher than the control group. However, the reduction of knowledge score was significantly higher in the lecture group (-13.0 ± 15.9% vs -5.7 ± 15.1%, p = .02). DISCUSSION: Educational interventions can improve nurses' knowledge of adverse drug reactions. Short-term learning could be achieved with lecture, but the retention of knowledge will be enhanced by simple interactive techniques.