Long and Short-term Metformin Consumption as a Potential Therapy to Prevent Complications of COVID-19.

Purpose: The aim of the study is to evaluate the effect of metformin in complication improvement of hospitalized patients with COVID-19. Methods: This was a randomized clinical trial that involved 189 patients with confirmed COVID-19 infection. Patients in the intervention group received metformin-500 mg twice daily. Patients who received metformin before admission were excluded from the control group. Patients who were discharged before taking at least 2000 mg of metformin were excluded from the study. Primary outcomes were vital signs, need for ICU admission, need for intubation, and mortality. Results: Data showed that patients with diabetes with previous metformin in their regimen had lower percentages of ICU admission and death in comparison with patients without diabetes (11.3% vs. 26.1% (P=0.014) and 4.9% vs. 23.9% (P≤0.001), respectively). Admission time characteristics were the same for both groups except for diabetes and hyperlipidemia, which were significantly different between the two groups. Observations of naproxen consumption on endpoints, duration of hospitalization, and the levels of spO2 did not show any significant differences between the intervention and the control group. The adjusted OR for intubation in the intervention group versus the control group was 0.21 [95% CI, 0.04-0.99 (P=0.047)]. Conclusion: In this trial, metformin consumption had no effect on mortality and ICU admission rates in non-diabetic patients. However, metformin improved COVID-19 complications in diabetic patients who had been receiving metformin prior to COVID-19 infection, and it significantly lowered the intubation rates.

The effects of virtual reality-based bronchoscopy simulator on learning outcomes of medical trainees: A systematic review.

Background and Aims: Conventional medical training routes of bronchoscopy may decrease patients' comfort and increase procedure-related morbidity. Virtual reality (VR)-based bronchoscopy is a beneficial and safe solution for teaching trainees. The aim of this systematic review was to study the effectiveness of VR-based bronchoscopy simulators on the learning outcomes of medical trainees. Methods: Well-known sources (i.e., Scopus, ISI Web of Science, and Medline via PubMed) were systematically searched using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines on December, 2021. Peer-reviewed English papers that used VR-based simulation for bronchoscopy training were included. The articles that were studying other technologies, or those that were unrelated to the topic, were excluded. The risk of bias was assessed using the Joanna Briggs Institute checklists for quasi-experimental studies and randomized controlled trials (RCTs). Results: Out of 343 studies, 8 of them met our inclusion criteria. An appropriate control group and statistical analysis were the most common and unavoidable sources of bias in included non-RCTs, and lack of blinding in participants was the most common source of bias in RCTs. The included studies evaluated learning outcomes regarding dexterity (N = 5), speed (N = 3), the accuracy of procedures (N = 1), and the need for verbal assistance (N = 1). Based on the results, 100% (5/5) and 66% (2/3) of studies showed that the use of VR-based simulation on the learning outcomes of medical trainees led to improvement in manual ability (i.e., dexterity) and swiftness of execution (i.e., speed in performance), respectively. Additionally, improving the accuracy of subjects' performance, and reducing the need for verbal guidance and physical assistance was reported in studies that evaluated these variables. Conclusion: VR bronchoscopy simulator as a training method for teaching medical trainees, especially for novices has the potential to improve medical trainees' performance and reduce complications. Further studies are needed to evaluate the positive effects of VR-based simulation on the learning outcomes of medical trainees.

Biomarkers in exhaled breath condensate as fingerprints of asthma, chronic obstructive pulmonary disease and asthma-chronic obstructive pulmonary disease overlap: a critical review.

Asthma, chronic obstructive pulmonary disease (COPD) and asthma-COPD overlap are the third leading cause of mortality around the world. They share some common features, which can lead to misdiagnosis. To properly manage these conditions, reliable markers for early and accurate diagnosis are needed. Over the past 20 years, many molecules have been investigated in the exhaled breath condensate to better understand inflammation pathways and mechanisms related to these disorders. Recently, more advanced techniques, such as sensitive metabolomic and proteomic profiling, have been used to obtain a more comprehensive understanding. This article reviews the use of targeted and untargeted metabolomic methodology to study asthma, COPD and asthma-COPD overlap.

Effect of vitamin A supplementation on the outcome severity of COVID-19 in hospitalized patients: A pilot randomized clinical trial.

INTRODUCTION: Vitamin A is one of the vitamins that is suggested as adjuvant therapy in viral infections due to its immune enhancing role. In the present clinical trial, we intended to assess the effect of vitamin A supplementation on Coronavirus disease-2019 (COVID-19) in hospitalized patients. METHODS: The present pilot randomized controlled clinical trial was conducted on 30 hospitalized patients with COVID-19. Patients in the intervention group received 50000 IU/day intramuscular vitamin A for a maximum of two weeks. Patients in the control group continued their common treatment protocols. All participants were followed up until discharge from the hospital or death. The primary outcome of the study was time to achieve clinical response based on the six classes of an ordinal scale. Time to clinical response was calculated based on the days needed to improve two scores on the scale or patient's discharge. RESULTS: The time to clinical response was not significantly different between the two groups (7.23 ± 2.14 vs. 6.75 ± 1.85 days, respectively, p = 0.48). There was no significant difference between the groups regarding clinical response (hazard ratio: 1.76 [95% CI: 0.73, 4.26]). There were no significant differences between groups regarding the need for mechanical ventilation, duration of hospitalization, or death in the hospital. CONCLUSION: The results of this pilot clinical trial showed no benefit of vitamin A compared with the common treatment on outcome severity in hospitalized patients with COVID-19. Although the results are negative, there is still a great need for future clinical studies to provide a higher level of evidence.

Global, regional, and national burden of cancers attributable to tobacco smoking in 204 countries and territories, 1990-2019.

BACKGROUND: Cancers are leading causes of mortality and morbidity, with smoking being recognized as a significant risk factor for many types of cancer. We aimed to report the cancer burden attributable to tobacco smoking by sex, age, socio-demographic index (SDI), and cancer type in 204 countries and territories from 1990 to 2019. METHODS: The burden of cancers attributable to smoking was reported between 1990 and 2019, based upon the Comparative Risk Assessment approach used in the Global Burden of Disease (GBD) study 2019. RESULTS: Globally, in 2019 there were an estimated 2.5 million cancer-related deaths (95% UI: 2.3 to 2.7) and 56.4 million DALYs (51.3 to 61.7) attributable to smoking. The global age-standardized death and DALY rates of cancers attributable to smoking per 100,000 decreased by 23.0% (-29.5 to -15.8) and 28.6% (-35.1 to -21.5), respectively, over the period 1990-2019. Central Europe (50.4 [44.4 to 57.6]) and Western Sub-Saharan Africa (6.7 [5.7 to 8.0]) had the highest and lowest age-standardized death rates, respectively, for cancers attributable to smoking. In 2019, the age-standardized DALY rate of cancers attributable to smoking was highest in Greenland (2224.0 [1804.5 to 2678.8]) and lowest in Ethiopia (72.2 [51.2 to 98.0]). Also in 2019, the global number of DALYs was highest in the 65-69 age group and there was a positive association between SDI and the age-standardized DALY rate. CONCLUSIONS: The results of this study clearly illustrate that renewed efforts are required to increase utilization of evidence-based smoking cessation support in order to reduce the burden of smoking-related diseases.

Exhaled breath condensate efficacy to identify mutations in patients with lung cancer: A pilot study.

Exhaled breath condensate (EBC) is used to investigate the efficacy of EBC to detect the genetic mutations in patients with lung cancer. Samples of 5 patients and 5 healthy volunteers were collected. DNA was extracted and used for amplification of hotspot regions of TP53 and KRAS genes by using PCR. We performed the mutation analysis by direct sequencing in all subjects. Detected mutations in EBC samples were compared with those of corresponding tumor tissues and there was complete agreement within the detected mutations in EBC and tumorous tissue. EBC can be used as an efficient and noninvasive source for the assessment of gene mutations in patients with lung cancer.

Psychological pathways between type D personality and COVID-19.

BACKGROUND: Patients with a type D personality have worse social functioning and mental health and more affective constraints than non-type D personalities. They have a negative outlook on life and health-related issues. The aim of this study was to examine the mediating role of stress and anxiety in the relationship between type D personality and COVID-19 by adjustment of the effect of demographic characteristics and perceived symptoms as confounder variables. PARTICIPANTS AND PROCEDURE: A total of 196 patients out of those suspected of having COVID-19 and visiting the reference hospitals were selected. They had completed the type D personality and the anxiety and stress scales along with their hospital admission form before undergoing COVID-19 testing. After their COVID-19 test, the participants were divided into two groups based on their disease, an infected group (n = 90) and a non-infected group (n = 106). RESULTS: Type D personality has no significant direct effect on infection with the disease, but taking into account the mediating variable of stress, the odds of an event in those with type D personality is 2.21 times higher than those without this personality (p = .027) and, taking into account the mediating variable of anxiety, having a type D personality increases the odds of an event by 2.62 times (p = .011), holding demographic characteristics and perceived symptoms constant. CONCLUSIONS: Given the indirect relationship between COVID-19 and type D personality, the mediating variables of stress and anxiety can be considered full mediating variables.

The early start of hemoperfusion decreases the mortality rate among severe COVID-19 patients: A preliminary study.

BACKGROUND: Coronavirus disease-2019 (COVID-19)-related organ failure is partly related to a sepsis-like syndrome and extreme pro-inflammatory cytokine release, named cytokine storm. Therapeutic strategies that prevent the production of or remove the pro-inflammatory cytokines could potentially be an effective therapy in critically afflicted COVID-19 patients. METHODS: In this clinical trial study, from April until June 2020, 68 COVID-19 patients (35 vs. 33 controls) with severe critical symptoms, and PaO2 /FiO2 (P/F) ratio less than 200 mmHg either received a single standard therapy or a combination of standard treatment for COVID-19 combined with hemoperfusion (hemofilter, HA330 D Javfron) for 4 h, in 3 consecutive days. The length of hospital stay and mechanical ventilation, the resolution of radiologic abnormalities, and the mortality rate were defined as the primary outcomes. RESULTS: Demographic characteristics, the acute physiology, and chronic health evaluation score of both groups were similar (p > 0.05). Importantly, we noticed a significant mortality rate reduction in the perfused group compared with controls (37.1% vs. 63.6%, p = 0.02), this positive effect was stronger among those with a P/F ratio higher than 75 (mortality rate of 84.7% for P/F ratio < 75 vs. 15.4% for P/F ratio ≥ 75, p = 0.02). CONCLUSIONS: The results imply that early start of hemoperfusion could be more effective and significantly reduce the mortality rate among COVID-19 patients with critical diseases.

Prevalence, Deaths, and Disability-Adjusted Life-Years Due to Asthma and Its Attributable Risk Factors in 204 Countries and Territories, 1990-2019.

BACKGROUND: Understanding global trends in the point prevalence, deaths, and disability-adjusted life-years (DALYs) for asthma will facilitate evidence-based decision-making. RESEARCH QUESTION: What are the global, regional, and national burdens of asthma in 204 countries and territories between 1990 and 2019 by age, sex, and sociodemographic index (SDI)? STUDY DESIGN AND METHODS: Publicly available data from the Global Burden of Disease study from 1990 through 2019 were used. All estimates were presented as counts and age-standardized rates per 100,000, along with their associated uncertainty intervals. RESULTS: In 2019, the global age-standardized point prevalence and death rates for asthma were 3,415.5 and 5.8 per 100,000, which represent a 24% and 51.3% decrease since 1990, respectively. Moreover, in 2019, the global age-standardized DALY rate was 273.6 and the global point prevalence of asthma was highest in the group 5 to 9 years of age. Also in 2019, the United States (10,399.3) showed the highest age-standardized point prevalence rate of asthma. Generally, the burden of asthma decreased with increasing SDI. Globally, high BMI (16.9%), smoking (9.9%), and occupational asthmagens (8.8%) contributed to the 2019 asthma DALYs. INTERPRETATION: Asthma remains an important public health issue, particularly in regions with low socioeconomic development. Future research is needed to examine thoroughly the associations asthma has with its risk factors and the factors impeding optimal self-management. Further research also is needed to understand and implement better the interventions that have reduced the burden of asthma.

Burden of Tracheal, Bronchus, and Lung Cancer and Its Attributable Risk Factors in 204 Countries and Territories, 1990 to 2019.

INTRODUCTION: Understanding trends in the annual incidence, mortality, and disability-adjusted life-years (DALYs) for tracheal, bronchus, and lung (TBL) cancer globally is important to enable appropriate targeting of resources for prevention, clinical practice improvement, and research. The aim of this study was to determine the global, regional, and national burdens of TBL cancer in 204 countries and territories from 1990 to 2019 by age, sex, and sociodemographic index. METHODS: Estimates were produced through various data inputs including the following: cancer registries (nsite-years = 5318), vital registration (nsite-years = 22,553), vital registration-sample (nsite-years = 825), and verbal autopsies (nsite-years = 516). Annual incidence, mortality, and DALYs were estimated and presented as counts and age-standardized rates per 100,000 population. RESULTS: There were 2.3 million (95% uncertainty interval [UI]: 2.1-2.5) incident cases of TBL cancer, with an age-standardized annual incidence rate of 27.7 (95% UI: 25.3-30), which decreased by 2.6% (95% UI: -12.4 to 6.5) between 1990 and 2019. TBL cancer was responsible for 2 million (95% UI: 1.9-2.2) deaths globally with an age-standardized death rate of 25.2 (95% UI: 23.2-27), a decrease of 7.8% (95% UI: -15.9 to 0.2) between 1990 and 2019. Moreover, TBL accounted for 45.9 million (95% UI: 42.3-49.3) DALYs at the global level, with an age-standardized rate of 551.6 (95% UI: 509-593.1) DALYs per 100,000 population. The standardized DALY rate declined by 16.2% (95% UI: -24 to -8.2) from 1990 to 2019. Greenland (77.7 [95% UI: 64.4-90.6]), Monaco (75.6 [95% UI: 61.4-90.8]), and Montenegro (56.7 [95% UI: 46.5-68.9]) had the three highest age-standardized annual incidence rates. The aforementioned three countries also had the three highest age-standardized death and DALY rates of TBL cancer. Honduras (68% [95% UI: 14.5-137.7]), Cabo Verde (62.2% [95% UI: 24.1-101.3]), and Monaco (58.2% [95% UI: 19.2-109.7]) had the largest increase in age-standardized annual incidence rates for TBL cancer during 1990 to 2019. The largest increases were found in age-standardized death rates of TBL cancer in Honduras (67.1% [95% UI: 14.7-133.1]), Cabo Verde (64.4% [95% UI: 25-103.4]), and Mozambique (49.9% [95% UI: 7.9 -101.3]). Age-standardized annual incidence and death rates were higher in male than female individuals and increased with population aging. There were nonlinear but generally positive associations between age-standardized DALY rates with corresponding sociodemographic index of countries. Globally, smoking (62.4%), ambient particulate matter (15.3%), and high fasting plasma glucose (9.9%) had the top three highest percent of attributable DALYs owing to TBL cancer in 2019 for both sexes. CONCLUSIONS: This study found a decline in burden globally but with some countries having an increase. These results are crucial to set priorities for prevention and treatment of TBL cancer and would be beneficial for policymakers, government officials, clinicians, and researchers.

Diabesity Associates with Poor COVID-19 Outcomes among Hospitalized Patients.

Background: Although numerous studies have investigated obesity's negative effect on coronavirus disease 2019 (COVID-19) outcomes, only a limited number focused on this association in diabetic patients. In this study, we analyzed the association between obesity and COVID-19 outcome (death, intensive care unit [ICU] admission, mechanical ventilation needs, quick Sequential Organ Failure Assessment [qSOFA] score, and confusion, urea, respiratory rate, blood pressure [CURB-65] scores) for hospitalized diabetic patients. Methods: In this prospective hospital-based registry of patients with COVID-19 in East Azerbaijan, Iran, 368 consecutive diabetic patients with COVID-19 were followed from admission until discharge or death. Self-reported weight and height were used to calculate body mass index (kg/m2) upon admission. Our primary endpoint was analyzing obesity and COVID-19 mortality association. Assessing the associations among obesity and disease severity, ICU admission, and mechanical ventilation was our secondary endpoint. Results: We analyzed data from 317 patients and found no significant difference between obese and non-obese patients regarding frequency of death, invasive mechanical ventilation, ICU admission, CURB-65, or qSOFA scores (P>0.05). After adjusting for confounding factors, obese diabetic COVID-19 patients were 2.72 times more likely to die than non-obese patients. Moreover, ventilator dependence (adjusted odds ratio [aOR], 1.87; 95% confidence interval [CI], 1.03-4.76) and ICU admission (aOR, 2.41; 95% CI, 1.11-5.68) odds were significantly higher for obese patients than non-obese patients. Conclusion: The results of the present study indicated that obesity worsens health outcomes for diabetic COVID-19 patients.

Comparison of losartan and amlodipine effects on the outcomes of patient with COVID-19 and primary hypertension: A randomised clinical trial.

BACKGROUND: Controversy exists regarding the drug selection in hypertension (HTN) management in patients with COVID-19. This study aimed to compare the effects of losartan and amlodipine in patients with primary HTN and COVID-19. METHODS: In this randomised clinical trial, hospitalised patients with COVID-19 and primary HTN were enrolled in the study. One arm received losartan, 25 mg, twice a day and the other arm received amlodipine, 5 mg per day for 2 weeks. The main outcomes were compare 30-day mortality rate and length of hospital stay. RESULTS: The mean age of patients treated with losartan (N = 41) and amlodipine (N = 39) was 67.3 ± 14.8 and 60.1 ± 17.3 years, respectively (P value = .068). The length of hospital stay in losartan and amlodipine groups was 4.57 ± 2.59 and 7.30 ± 8.70 days, respectively (P value = .085). Also, the length of ICU admission in losartan and amlodipine group was 7.13 ± 5.99 and 7.15 ± 9.95 days, respectively (P value = .994). The 30-day mortality was two and five patients in losartan and amlodipine groups, respectively (P value = .241). CONCLUSIONS: There was no priority in losartan or amlodipine administration in COVID-19 patients with primary HTN in decreasing mortality rate, hospital and ICU length stay. Further studies need to clarify the first-line anti-HTN medications in COVID-19.

Th17 and Treg cells function in SARS-CoV2 patients compared with healthy controls.

In the course of the coronavirus disease 2019 (COVID-19), raising and reducing the function of Th17 and Treg cells, respectively, elicit hyperinflammation and disease progression. The current study aimed to evaluate the responses of Th17 and Treg cells in COVID-19 patients compared with the control group. Forty COVID-19 intensive care unit (ICU) patients were compared with 40 healthy controls. The frequency of cells, gene expression of related factors, as well as the secretion levels of cytokines, were measured by flow cytometry, real-time polymerase chain reaction, and enzyme-linked immunosorbent assay techniques, respectively. The findings revealed a significant increase in the number of Th17 cells, the expression levels of related factors (RAR-related orphan receptor gamma [RORγt], IL-17, and IL-23), and the secretion levels of IL-17 and IL-23 cytokines in COVID-19 patients compared with controls. In contrast, patients had a remarkable reduction in the frequency of Treg cells, the expression levels of correlated factors (Forkhead box protein P3 [FoxP3], transforming growth factor-ß [TGF-ß], and IL-10), and cytokine secretion levels (TGF-ß and IL-10). The ratio of Th17/Treg cells, RORγt/FoxP3, and IL-17/IL-10 had a considerable enhancement in patients compared with the controls and also in dead patients compared with the improved cases. The findings showed that enhanced responses of Th17 cells and decreased responses of Treg cells in 2019-n-CoV patients compared with controls had a strong relationship with hyperinflammation, lung damage, and disease pathogenesis. Also, the high ratio of Th17/Treg cells and their associated factors in COVID-19-dead patients compared with improved cases indicates the critical role of inflammation in the mortality of patients.

Value of Canadian C-spine rule versus the NEXUS criteria in ruling out clinically important cervical spine injuries: derivation of modified Canadian C-spine rule.

PURPOSE: Although, Canadian C-spine rule and the National Emergency X-Radiography Utilization Study (NEXUS) criteria in ruling out clinically important cervical spine injuries have been validated using large prospective studies, no consensus exist as to which rule should be endorsed. Therefore, the aim of the present study was to compare the accuracy of the Canadian C-spine and NEXUS criteria in ruling out clinically important cervical spine injuries in trauma patients. Finally, we introduced the modified Canadian C-spine rule. METHODS: A prospective diagnostic accuracy study was conducted on trauma patients referred to four emergency departments of Iran in 2018. Emergency physicians evaluated the patients based on the Canadian C-spine rule and NEXUS criteria in two groups of low risk and high risk for clinically important cervical spine injury. Afterward, all patients underwent cervical imaging. In addition, modified Canadian C-spine rule was derived by removing dangerous mechanism and simple rear-end motor vehicle collision from the model. RESULTS: Data from 673 patients were included. The area under the curve of the NEXUS criteria, Canadian C-spine, and modified Canadian C-spine rule were 0.76 [95% confidence interval (CI) 0.71-0.81)], 0.78 (95% CI 0.74-0.83), and 0.79 (95% CI 0.74-0.83), respectively. The sensitivities of NEXUS criteria, Canadian C-spine, and modified Canadian C-spine rule were 93.4%, 100.0% and 100.0%, respectively. CONCLUSIONS: The modified Canadian C-spine rule has fewer variables than the original Canadian C-spine rule and is entirely based on physical examination, which seems easier to use in emergency departments.

Incidence of symptomatic venous thromboembolism following hospitalization for coronavirus disease 2019: Prospective results from a multi-center study.

BACKGROUND: Thrombosis and pulmonary embolism appear to be major causes of mortality in hospitalized coronavirus disease 2019 (COVID-19) patients. However, few studies have focused on the incidence of venous thromboembolism (VTE) after hospitalization for COVID-19. METHODS: In this multi-center study, we followed 1529 COVID-19 patients for at least 45 days after hospital discharge, who underwent routine telephone follow-up. In case of signs or symptoms of pulmonary embolism (PE) or deep vein thrombosis (DVT), they were invited for an in-hospital visit with a pulmonologist. The primary outcome was symptomatic VTE within 45 days of hospital discharge. RESULTS: Of 1529 COVID-19 patients discharged from hospital, a total of 228 (14.9%) reported potential signs or symptoms of PE or DVT and were seen for an in-hospital visit. Of these, 13 and 12 received Doppler ultrasounds or pulmonary CT angiography, respectively, of whom only one patient was diagnosed with symptomatic PE. Of 51 (3.3%) patients who died after discharge, two deaths were attributed to VTE corresponding to a 45-day cumulative rate of symptomatic VTE of 0.2% (95%CI 0.1%-0.6%; n = 3). There was no evidence of acute respiratory distress syndrome (ARDS) in these patients. Other deaths after hospital discharge included myocardial infarction (n = 13), heart failure (n = 9), and stroke (n = 9). CONCLUSIONS: We did not observe a high rate of symptomatic VTE in COVID-19 patients after hospital discharge. Routine extended thromboprophylaxis after hospitalization for COVID-19 may not have a net clinical benefit. Randomized trials may be warranted.