Bosentan for high-risk outpatients with COVID-19 infection: a randomized, double blind, placebo-controlled trial.

Background: The endothelium is supposedly activated and damaged in COVID-19 because of endothelin-1 over-secretion. This study evaluates the effect of bosentan as an endothelin receptor blocker on the progression of disease in high-risk outpatients with COVID-19 infection. Methods: From 15 December 2021 to 15 May 2022, high-risk outpatients were randomly assigned to receive bosentan, 62.5 mg or placebo twice daily from enrollment for 30 days. Both groups received standard medical treatment too. On day 30 of the trial, the patients underwent complete doppler ultrasound of the lower extremities to detect asymptomatic thromboembolic events. The primary outcome in this study was hospitalization or death from any cause within the first 15 days. Secondary outcomes included thromboembolic events, hospital-free days and death from any cause within 30 days after randomization (IRCT.ir, IRCT20211203053263N1). Findings: Basal characteristics of the two groups were similar. Primary outcomes occurred in 3 (2.3%) of the 129 patients in the bosentan group versus 15 (11.5%) of the 130 patients in the placebo group [risk difference: -9.2% (95% CI: -15.3 to -3.1), P = 0.006]. Median hospital-free days was significantly higher in the bosentan group (P = 0.004). A total of three deaths occurred and all were in the control group. Bosentan was associated with a nonsignificant reduction in mortality compared with placebo (P = 0.24). Thromboembolic events occurred in one (1%) of 97 patients in the bosentan group versus nine (8.7%) of 104 patients in the placebo group within 30 days after randomization [risk difference: -8.3% (95% CI: -14.4 to -2.2), P = 0.008]. Interpretation: Early administration of bosentan may prevent disease progression and thromboembolic events in high-risk outpatients with COVID-19. Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Refeeding Syndrome and Its Related Factors in Critically Ill Coronavirus Disease 2019 Patients: A Prospective Cohort Study.

Background and Aim: Malnutrition and its complications is usually neglected in critically ill COVID-19 patients. We conducted the present study to investigate the prevalence of refeeding syndrome and its related factors in this group of patients. Methods: In this prospective cohort study, 327 patients were assessed for being at risk and developing refeeding syndrome. The criteria was ASPEN consensus recommendations for refeeding syndrome released in 2020. Malnutrition was assessed based on global leadership initiative on malnutrition (GLIM) criteria. The relation between actual protein, calorie intake, and refeeding syndrome was also evaluated via cox regression model. The data concerning calorie and protein intake were gathered for 5 days after initiating feeding. The daily protein and calorie intake were divided by kilogram body weight in order to calculate the actual protein (g/kg/day) and energy (kcal/kg/day) intake. Results: Among the subjects, 268 (82%) were at risk of refeeding syndrome and 116 (36%) got involved in this syndrome. Malnutrition, according to the GLIM criteria, was found in 193 (59%) of the subjects. In the at-risk population, the risk of refeeding syndrome was reduced by 90% with the rise in protein intake (CI; 0.021-0.436, P = 0.002), increased by 1.04 times with the increase in age (CI; 1.032-1.067, P < 0.001), and by 1.19 times with the rise in the days from illness onset to admission (CI; 1.081-1.312, P < 0.001) in adjusted cox model analysis. Conclusion: The incidence of refeeding syndrome is relatively high, which threatens the majority of critically ill COVID-19 patients. Increased protein intake was found to reduce the occurrence of refeeding syndrome.

Implementation of a Case Presentation Program for Clinical Nutrition Students.

Background and Aims: To implement a training method increase clinical nutritionists' knowledge and make doctors more familiar with this specialty. Methods: The study was conducted in an internship course of all third semester clinical nutrition students. At first, conventional training was presented for students, and then, in the same duration, case presentation training program was implemented. The presentations were filmed and uploaded to the Internet, and the link was placed on the hospital's website. At the end of the 2 phases, the students were asked to answer the survey questionnaire. Additionally, consultation report sheets were evaluated and scored by 2 physicians. Number of consultation requests was also recorded in 2 study phases. Results: The mean satisfaction score was statistically higher in the case presentation training program than in the conventional program. All the students recommended similar case report program courses for the students in the future. Although the mean consultation report score was not statistically different between the two training programs, case presentation program resulted in significantly better scores in 4 items of nutrition focused physical examinations, assessment of malnutrition, assessment of related laboratory tests, and food-drug interactions. Number of consultation requests was significantly increased during the case presentation program training compared to the conventional training from 194 to 272 (P < 0.001). Conclusion: From the students' perspective, the case-based learning report was preferred to the conventional method. From the physicians' viewpoint, the answer to the counseling sheets was more complete and helpful.

Ketorolac and Predicted Severe Acute Pancreatitis: A Randomized, Controlled Clinical Trial.

Objective: We evaluated the effect of ketorolac on reducing the severity of acute pancreatitis.Design and Setting: Randomized clinical trial performed in a University hospital.Participants: There were 56 adult patients, with predicted severe acute pancreatitis, randomly divided into two groups.Methods: The patients in the study group received intravenous ketorolac, 10 mg, three times daily from the time of enrollment for a maximum of 5 days, as needed, along with standard medical treatment. Primary outcome measure was the change in the serum level of high sensitive C-reactive protein (hs-CRP). Patients were also followed up in terms of hospitalization duration, need for intensive care unit (ICU), organ failure development, persistent organ failure, pancreatic necrosis, nutritional assessment, and mortality. The study continued to gather clinical follow-up information up to 4 months.Results: Serum level of hs-CRP was significantly lower in the ketorolac group compared with the control group on days 3, 4, and 5. There were no significant differences in organ failure, pseudocyst formation, acute necrotic collection, mortality, and ICU transfer between groups. Days of hospitalization were significantly lower in the study group. The feeding start time was significantly shorter in the study group with no need for tube feeding in the ketorolac group. Frequency of NPO (not per oral) was significantly lower in the ketorolac group.Conclusion: The use of ketorolac may improve feeding outcomes and shorten length of hospitalization in predicted severe acute pancreatitis.

Ascorbic Acid to Prevent Postpolypectomy Bleeding in the Colon: A Randomized Controlled Trial.

INTRODUCTION: It has been reported that vitamin C replacement can quickly reverse nonspecific bleeding in surgical patients with normal coagulation parameters. We evaluated the effect of intravenous ascorbic acid administration for prevention of postpolypectomy bleeding in large polyps of the colon. MATERIALS AND METHODS: Patients with large polyps with heads larger than 10 mm, stalk diameter larger than 5 mm, and a length larger than 10 mm were included in this randomized controlled clinical trial. In the study group, the first 500 mg intravenous dose of vitamin C diluted in normal saline was administered 2 h before colonoscopic resection of polyps and the second and third similar doses were administered on days 2 and 3 of polypectomy, respectively. The control group received normal saline in a similar fashion. The resection of polyps was performed in snare and cut-blend mode. Early and late postoperative bleeding were compared between the two groups. RESULTS: A total of 153 polyps were resected by endoscopic polypectomy. Early bleeding was observed in 7.2% of the patients, which was significantly lower in the vitamin C group (2.6% vs 11.8%, P = 0.03). Late bleeding was observed in 6.5% of the patients with a trend lower in the vitamin C group (2.6% vs 10.5%, P = 0.057). The proportion of postprocedural bleeding was significantly higher in the vitamin C group (5% vs 20%, P = 0.007). Hazard ratios of early and postprocedural bleeding were 78% and 76% lower in the vitamin C group compared to the control group (P < 0.05). CONCLUSION: Intravenous ascorbic acid infusion could reduce postpolypectomy bleeding.

Protein and Energy Intake Assessment and Their Association With In-Hospital Mortality in Critically Ill COVID-19 Patients: A Prospective Cohort Study.

Background and Aim: It is partially known that nutritional intake could alleviate proteolysis and course of disease severity in patients with COVID-19; however, not enough data are available in this regard. The present study aimed to assess protein and energy intake and their association with in-hospital mortality in critically ill COVID-19 patients. Methods: A total of 126 patients with COVID-19, who were critically ill, ≥5 days and a subset of 111 patients in ICU ≥10 days completed the present prospective observational cohort study. Results: Protein and energy intakes on Day 5 of ICU admission in survivors were 46 and 58% of target values, respectively. These values in non-survivors were 42 and 50% of target values, respectively (p < 0.05). In the sample ≥10 days, protein and energy intakes in survivors reached 64 and 87% of target values, respectively, without statistically significant differences with non-survivors. In the sample ≥5 days, Cox proportional hazard regression was adjusted for GLIM, APACHE II, comorbidity, and age; the results indicated that the patients with protein and energy intake lower than 0.59 g/kg/day and 14 kcal/kg/day, had ~2-fold mortality hazard (protein: HR, 2.38; 95% CI, 1.40-4.03; P = 0.001 and energy: HR, 2.23; 95% CI, 1.27-3.92; P = 0.005). Conclusion: Actual protein and energy intakes in critically ill patients with COVID-19 are in suboptimal levels compared with goal recommendations in these patients. Moreover, higher amounts of protein and energy intakes in the early acute phase were significantly associated with better survival and lower risk of in-hospital mortality.

The validity of the global leadership initiative on malnutrition criteria for diagnosing malnutrition in critically ill patients with COVID-19: A prospective cohort study.

BACKGROUND AND AIM: We conducted the present study to investigate the nutritional status of critically ill COVID-19 patients and validate the GLIM criteria with respect to the SGA. METHODS: In this prospective cohort study, 109 ICU patients were assessed for malnutrition based on GLIM and SGA criteria. The relation between nutrition assessment tools and duration of hospitalization and mortality were also evaluated. The sensitivity and specificity of GLIM criteria concerning the detection of malnutrition was assessed based on the area under the curve. RESULTS: Malnutrition, according to the SGA and GLIM criteria, was found in 68 (62.4%) and 66 (61.5%) of our subjects. There was an optimal agreement between the GLIM criteria and the SGA criteria regarding malnutrition diagnosis (K = 0.85, P < 0.001). The area under curve for the GLIM was stratified based on the SGA results and was 0.927 (95% CI: 0.868-0.985) with a sensitivity and specificity of 92% and 93%, respectively. CONCLUSION: Malnutrition is frequently observed in critically ill COVID-19 patients. GLIM criteria is a valid tool and has a strong association with mortality and longer duration of ICU stay.

Combination of APACHE Scoring Systems with Adductor Pollicis Muscle Thickness for the Prediction of Mortality in Patients Who Spend More Than One Day in the Intensive Care Unit.

BACKGROUND: The objective of the present study was to compare the ability of Acute Physiology and Chronic Health Evaluation (APACHE) scoring systems with the combination of an anthropometric variable score "adductor pollicis muscle (APM) thickness" to the APACHE systems in predicting mortality in the intensive care unit. METHODS: A prospective observational study was conducted with the APM thickness in the dominant hand, and APACHE II and III scores were measured for each patient upon admission. Given scores for the APM thickness were added to APACHE score systems to make two composite scores of APACHE II-APM and APACHE III-APM. The accuracy of the two composite models and APACHE II and III systems in predicting mortality of patients was compared using the area under the ROC curve. RESULTS: Three hundred and four patients with the mean age of 54.75 ± 18.28 years were studied, of which 96 (31.57%) patients died. Median (interquartile range) of APACHE II and III scores was 15 (12-20) and 47 (33-66), respectively. Median (interquartile range) of APM thickness was 15 (12-17) mm, respectively. The area under the ROC curves for the prediction of mortality was 0.771 (95% CI: 0.715-0.827), 0.802 (95% CI: 0.751-0.854), 0.851 (95% CI: 0.807-0.896), and 0.865 (95% CI: 0.822-0.908) for APACHE II, APACHE III, APACHE II-APM, and APACHE III-APM, respectively. CONCLUSION: Although improvements in the area under ROC curves were not statistically significant when the APM thickness added to the APACHE systems, but the numerical value added to AUCs are considerable.

Transcultural Adaptation and Validation of Persian Version of Celiac Disease Questionnaire (CDQ); A Specific Questionnaire to Measure Quality of Life of Iranian Patients.

BACKGROUND: The assessment of health-related quality of life has become an important primary or secondary outcome measure in clinical and epidemiologic studies. The aim of this study was to validate a Persian version of Celiac Disease Questionnaire (CDQ) for Celiac disease (CD) among Iranian patients. MATERIALS AND METHODS: The English version of the CDQ adapted to the Persian language by a forward-backward translation by 3 professional bilingual translators (1 medical, 2 nonmedical). The content validity of translated questionnaire were studied by 5 experts who complete the validity form regarding the questionnaire. Then in a pilot study, translated CDQ completed by 81 CD patients who referred to Taleghani Hospital, Tehran. For assessing the validity and reliability of the questionnaire, confirmatory factor analysis and Cronbach's alpha coefficient have been done, using Lisrel and SPSS software. RESULTS: Of 81 CD patients entered to this study with mean age of 30.54 years old, 71.6% were female. Also, 56.8% were married and 45.7% were high educated. The mean of CDQ total score was 119.18±34. The calculated Cronbach's alpha coefficient for CDQ questionnaire was 0.9. Also, for each subgroups the Cronbach's alpha coefficient were calculated as the following; emotion: 0.92, Social: 0.89, Worries: 0.73, Gastrointestinal: 0.78. Confirmatory factor analysis indicated that all questions could be remain in questionnaire respectively. CONCLUSION: The reliability of the Persian version of CDQ was excellent with Cronbach's alpha coefficients and Persian version of CDQ retains the psychometric properties of the original instrument and should be useful to assess outcome in studies and clinical trials involving Iranian patients with CD.

Comparison between daily single-dose triple therapy and conventional triple therapy on patient compliance and Helicobacter pylori eradication: A randomized controlled trial.

OBJECTIVE: The poor compliance to treatment of Helicobacter pylori-infected patients is well-known. We evaluated the efficacy of daily single-dose triple therapy as compared to conventional triple therapy on patient compliance and eradication of H. pylori infection. METHODS: In the study group, 105 patients received esomeprazole 40 mg, tinidazole 1 g, and levofloxacin 500 mg once-daily for 14 days. One hundred and seven patients in the control group received lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg twice-daily for 14 days. Four weeks after completing therapy, urea breath test was performed to assess the eradication of H. pylori infection. RESULTS: The eradication rates by intention-to-treat analysis were 86% and 90.2% and by per-protocol analyses were 90.5% and 95.3% in the control and study groups, respectively, with no significant differences. Drug compliance was significantly better in the study group compared to the control group (p = 0.04). Overall, 44.7% of the patients in the study and 47.6% in the control groups had at least one adverse event. The most common adverse event was the dysgeusia in both the groups. The occurrence of diarrhea, nausea and vomiting was significantly higher in the control group and that of arthralgia was higher in the study group. The presence of periodontal disease and drug compliance was independently associated with treatment failure. CONCLUSION: The use of single-dose PPI-based triple therapy improves drug compliance and eradication rate to standard PPI-based triple therapy. Presence of periodontal disease and drug compliance had negative influence on the eradication rate. TRIAL REGISTRATION: NCT02711176 ᅟ ᅟ.

Effect of enteral feeding with ginger extract in acute respiratory distress syndrome.

PURPOSE: The purpose of this study is to evaluate the effects of an enteral diet enriched with ginger extract on inflammatory factors, respiratory profile, and outcome of patients with acute respiratory distress syndrome (ARDS). MATERIALS AND METHODS: Thirty-two patients with ARDS were randomized to receive a high-protein enteral diet enriched with ginger or placebo. Serum levels of interleukin (IL) 1, IL-6, tumor necrosis factor α, and leukotriene B4; red blood cell glutathione; oxygenation; and static compliance were measured on days 0, 5, and 10. RESULTS: Patients fed enteral diet enriched with ginger had significantly lower serum levels of IL-1, IL-6, and tumor necrosis factor α and higher level of RBC glutathione on days 5 and 10 compared with control group (P < .05). Significant improvement in oxygenation was observed on day 5 (P = .02) and 10 (P = .003) in ginger group compared with control group. Static compliance was increased on day 5 (P = .01) in ginger group compared with control group. A significant difference was found in duration of mechanical ventilation (P = .02) and length of intensive care unit stay (P = .04) in favor of ginger group. We did not find any difference in barotraumas, organ failure, and mortality between the study groups. CONCLUSIONS: An enteral diet supplemented with ginger in patients with ARDS may be beneficial for gas exchange and could decrease duration of mechanical ventilation and length of stay in intensive care unit.

Effect of fasting with two meals on BMI and inflammatory markers of metabolic syndrome.

The metabolic syndrome has been recognized as a proinflammatory state and inflammatory markers are associated with an increased risk for subsequent cardiovascular disease and type 2 diabetes. The aim of this clinical trial study was to evaluate the effect of Ramadan fasting on High-sensitive C-reactive Protein (hs-CRP) and fibrinogen levels in metabolic syndrome. Sixty five male with metabolic syndrome who were admitted to Hospital were selected for the study. Waist circumference, BMI, FPG, HDL-C, TG, fibrinogen and hs-CRP were evaluated before and after month of Ramadan. The duration of study was thirty days. The dietary intake was estimated by 24 h recall before and after fasting. Metabolic syndrome was diagnosed using the ATP III criteria. FPG, HDL-C, fibrinogen, hs-CRP, BMI and waist circumference were decreased significantly after study (p = 0.005, p = 0.002, p = 0.02, p = 0.01, p = 0.01, p = 0.01, respectively). There was no change in serum TG level (p = 0.21). Simple linear regression analysis demonstrated that after fasting, hs-CRP was related to waist circumference and BMI (r = 0.388, p = 0.01 and r = -0.439, p = 0.02, respectively). Change in the number and timing of meals and portioning the entire intake into two without changing the total energy consumption may have beneficial effects on anthropometry measures and inflammatory markers of metabolic syndrome.

Ginger extract reduces delayed gastric emptying and nosocomial pneumonia in adult respiratory distress syndrome patients hospitalized in an intensive care unit.

PURPOSE: The purpose of this study was to evaluate the effect of ginger extract on delayed gastric emptying, developing ventilator-associated pneumonia, and clinical outcomes in adult respiratory distress syndrome (ARDS). MATERIALS AND METHODS: Thirty-two ARDS patients who were dependent on mechanical ventilation and fed via nasogastric tube were studied. After enrollment, patients were randomized to 2 groups. The control group received 1 g of coconut oil as placebo, and the study group received 120 mg of ginger extract. The amount of feeding tolerated at the first 48 hours of feeding, amount of feeding tolerated during the entire study period, nosocomial pneumonia, number of intensive care unit (ICU)-free days, number of ventilator-free days, and mortality were evaluated during 21 days of intervention. RESULTS: There was a significant difference between the ginger group and the control group in the amount of feeding tolerated at the first 48 hours of enteral feeding (51% vs 57%, P < .005). There was a trend toward a decrease in pneumonia in the ginger group (P = .07). The overall in-ICU mortality was 15.6%, with no significant difference in the 2 groups. The number of ventilator-free days and that of ICU-free days were lower in the control group compared with the ginger group (P = .04 and P = .02). CONCLUSION: This study showed that gastric feed supplementation with ginger extract might reduce delayed gastric emptying and help reduce the incidence of ventilator-associated pneumonia in ARDS.