Efficacy of Oral Mucoadhesive N-Acetylcysteine Tablets in Treatment of Recurrent Aphthous Stomatitis: A Randomized Double-Blind, Placebo-Controlled Clinical Trial.

Objectives: This study aimed to assess the efficacy of oral mucoadhesive N-acetylcysteine (NAC) tablets for treatment of recurrent aphthous stomatitis (RAS). Materials and Methods: Forty-nine patients with RAS were randomized to receive mucoadhesive NAC tablets (n=25) or placebo (n=24). Tablets were prescribed three times a day for 7 days in each group. Pain intensity was evaluated with visual analog scale (VAS) three times a day from day 1 to day 7. Also, patients were clinically examined on days 0 (before entering the study), 3, 5, and 7 using a metal caliper to measure the diameter of the lesions. The data were statistically analyzed and P<0.05 was considered statistically significant. Results: Regarding the VAS score, all participants in the treatment group showed complete recovery on day 7 (P<0.01). Also, the diameter of the lesions was significantly smaller in the treatment group than the placebo group at the end of the study (P<0.001). Conclusion: The results of this clinical trial showed for the first time that mucoadhesive NAC tablets can significantly decrease pain and the diameter of RAS lesions without any systemic complications.

Inhalation phage therapy as a new approach to preventing secondary bacterial pneumonia in patients with moderate to severe COVID-19: A double-blind clinical trial study.

Inhalation phage therapy is proposed as a replacement approach for antibiotics in the treatment of pulmonary bacterial infections. This study investigates phage therapy on bacterial pneumonia in patients with moderate to severe COVID-19 via the inhalation route. In this double-blind clinical trial, 60 patients with positive COVID-19 hospitalized in three central Mazandaran hospitals were chosen and randomly divided into two intervention and control groups. Standard country protocol drugs plus 10 mL of phage suspension every 12 h with a mesh nebulizer was prescribed for 7 days in the intervention group. The two groups were compared in terms of O2Sat, survival rate, severe secondary pulmonary bacterial infection and duration of hospitalization. Comparing the results between the intervention and control group, in terms of the trend of O2Sat change, negative sputum culture, no fever, no dyspnea, duration of hospitalization, duration of intubation and under ventilation, showed that the difference between these two groups was statistically different (P value < 0.05). In conclusion, inhalation phage therapy may have a potential effect on secondary infection and in the outcome of COVID-19 patients. However, more clinical trials with control confounding factors are needed to further support this concept.

Non-effectiveness of Ivermectin on Inpatients and Outpatients With COVID-19; Results of Two Randomized, Double-Blinded, Placebo-Controlled Clinical Trials.

Background: Ivermectin which was widely considered as a potential treatment for COVID-19, showed uncertain clinical benefit in many clinical trials. Performing large-scale clinical trials to evaluate the effectiveness of this drug in the midst of the pandemic, while difficult, has been urgently needed. Methods: We performed two large multicenter randomized, double-blind, placebo-controlled clinical trials evaluating the effectiveness of ivermectin in treating inpatients and outpatients with COVID-19 infection. The intervention group received ivermectin, 0.4mg/kg of body weight per day for 3 days. In the control group, placebo tablets were used for 3 days. Results: Data for 609 inpatients and 549 outpatients were analyzed. In hospitalized patients, complete recovery was significantly higher in the ivermectin group (37%) compared to placebo group (28%; RR, 1.32 [95% CI, 1.04-1.66]; p-value = 0.02). On the other hand, the length of hospital stay was significantly longer in the ivermectin group with a mean of 7.98 ± 4.4 days compared to the placebo receiving group with a mean of 7.16 ± 3.2 days (RR, 0.80 [95% CI, 0.15-1.45]; p-value = 0.02). In outpatients, the mean duration of fever was significantly shorter (2.02 ± 0.11 days) in the ivermectin group versus (2.41 ± 0.13 days) placebo group with p value = 0.020. On the day seventh of treatment, fever (p-value = 0.040), cough (p-value = 0.019), and weakness (p-value = 0.002) were significantly higher in the placebo group compared to the ivermectin group. Among all outpatients, 7% in ivermectin group and 5% in placebo group needed to be hospitalized (RR, 1.36 [95% CI, 0.65-2.84]; p-value = 0.41). Also, the result of RT-PCR on day five after treatment was negative for 26% of patients in the ivermectin group versus 32% in the placebo group (RR, 0.81 [95% CI, 0.60-1.09]; p-value = 0.16). Conclusion: Our data showed, ivermectin, compared with placebo, did not have a significant potential effect on clinical improvement, reduced admission in ICU, need for invasive ventilation, and death in hospitalized patients; likewise, no evidence was found to support the prescription of ivermectin on recovery, reduced hospitalization and increased negative RT-PCR assay for SARS-CoV-2 5 days after treatment in outpatients. Our findings do not support the use of ivermectin to treat mild to severe forms of COVID-19. Clinical Trial Registration: www.irct.ir IRCT20111224008507N5 and IRCT20111224008507N4.

Effects of Ivermectin in Patients With COVID-19: A Multicenter, Double-blind, Randomized, Controlled Clinical Trial.

PURPOSE: Given the coronavirus disease 2019 (COVID-19) pandemic, there is a global urgency to discover an effective treatment for patients withthis disease. This study aimed to evaluate the effects of the widely used antiparasitic drug ivermectin on outcomes in patients with COVID-19. METHODS: In this randomized, double-blind clinical trial, patients with COVID-19 admitted to 2 referral tertiary hospitals in Mazandaran, Iran, were randomly divided into 2 groups: intervention and control. In addition to standard treatment for COVID-19, the intervention group received a single weight-based dose (0.2 mg/kg) of ivermectin; the control group received the standard of care. Demographic, clinical, laboratory, and imaging data from participants were recorded at baseline. Patients were assessed daily for symptoms and disease progression. The primary clinical outcome measures were the durations of hospital stay, fever, dyspnea, and cough; and overall clinical improvement. FINDINGS: Sixty-nine patients were enrolled (mean [SD] ages: ivermectin, 47.63 [22.20] years; control, 45.18 [23.11] years; P = 0.65). Eighteen patients (51.4%) in the ivermectin group and 18 (52.9%) in control group were male (P = 0.90). The mean durations of dyspnea were 2.6 (0.4) days in the ivermectin group and 3.8 (0.4) days in the control group (P = 0.048). Also, persistent cough lasted for 3.1 (0.4) days in the ivermectin group compared to 4.8 (0.4) days in control group (PP = 0.019). The mean durations of hospital stay were 7.1 (0.5) days versus 8.4 (0.6) days in the ivermectin and control groups, respectively (P = 0.016). Also, the frequency of lymphopenia decreased to 14.3% in the ivermectin group and did not change in the control group (P = 0.007). IMPLICATIONS: A single dose of ivermectin was well-tolerated in symptomatic patients with COVID-19, and important clinical features of COVID-19 were improved with ivermectin use, including dyspnea, cough, and lymphopenia. Further studies with larger sample sizes, different drug dosages, dosing intervals and durations, especially in different stages of the disease, may be useful in understanding the potential clinical benefits ivermectin. Iranian Registry of Clinical Trials identifier: IRCT20111224008507N3.

Relationship Between Selenium Trace and Patient Outcome After Open-Heart Surgery.

BACKGROUND: Acute stress response to heart surgery can cause major morbidity in patients. The trace of selenium is useful for preventing heart damage. Although the trend of selenium changes is of high importance for body balance, the usefulness of routine use and effectiveness of this element for patients under open-heart surgery is still unclear. OBJECTIVES: This study aimed at assessing serum selenium level before and after open-heart surgery and the relationship between selenium trace and patient outcome. METHODS: This prospective analytical study was performed on 100 patients undergoing open-heart surgery using cardiopulmonary bypass (CPB). In all patients, the serum level was measured at a predetermined time (before surgery and one and two days after surgery). Then, the relationship between serum selenium and patient outcome was assessed. RESULTS: The mean serum selenium level in patients on admission was 72.90 ± 14.62 µg/L, one day after surgery was 71.20 ± 15.84 µg/L, and two days after surgery was 71.54 ± 15.97 µg/L. Serum selenium levels were inversely and significantly associated with age (r = -0.183; P = 0.034, 013) duration of surgery (r = -221 and P = 0.014), duration of intensive care unit stay (r = 0.204, P = 0.021), and duration of CPB (r = 0.223, P = 013). CONCLUSIONS: Based on this study's results, a low level of selenium can affect patients' outcomes after open-heart surgery.

Evaluation of zinc sulfate mucoadhesive formulation on recurrent aphthous stomatitis: a randomized double-blind, placebo-controlled clinical trial.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is a common lesion that affects the oral mucosa. There are several methods to treat RAS, including systemic and topical formulations. This study was conducted to evaluate the anti-inflammatory effect of topical zinc sulfate and its efficacy in the treatment of RAS. METHODS: A double-blind randomized clinical trial was conducted on 46 patients with RAS. They were randomly assigned into two groups to receive a zinc sulfate mucoadhesive tablet or placebo for 7 days. The pain severity was measured at baseline and daily while the diameter of the lesion was measured at baseline and on days 3, 5, and 7. The obtained data were analyzed in SPSS V.16. RESULTS: There was no significant difference in the mean diameter of lesions and pain at baseline between the two groups (P = 0.643 and P = 0.842, respectively). However, on the third, fifth, and seventh days of the study, the diameter of the lesion significantly reduced in the intervention group (P = 0.001) and the pain intensity became significantly different between groups from the fourth day of the study (P = 0.001). CONCLUSION: Zinc sulfate mucoadhesive tablet was effective in recovery and reducing the pain and diameter of the aphthous lesion and could be considered for the treatment of RAS. TRIAL REGISTRATION: Evaluation of the effectiveness of zinc sulfate mucoadhesive tablet in the improvement of recurrent aphthous stomatitis (RAS), IRCT20151109024975N9. Registered August 1, 2018, https://en.irct.ir/trial/32423 . This project was registered by the Iranian Registry of Clinical Trials ( http://www.irct.ir ). The IRCT ID was IRCT20151109024975N9.

Multidrug and co-resistance patterns of non-fermenting Gram-negative bacilli involved in ventilator-associated pneumonia carrying class 1 integron in the North of Iran.

INTRODUCTION: Ventilator-associated pneumonia (VAP) due to non-fermenting Gram-negative bacilli (NFGNB), especially Pseudomonas aeruginosa and Acinetobacter spp., is one of the main hospital-acquired infections leading to mortality and morbidity, especially in intensive care units (ICUs). This study seeks to determine the multidrug and co-resistance (MDR) patterns of NFGNB that are agents of VAP, and assess the presence of class 1 integron in these bacteria. METHODS: This cross-sectional study involved VAP patients admitted in the ICUs of 18 hospitals in the Mazandaran province, located in the North of Iran. The antibiotic susceptibility pattern was determined by the minimum inhibitory concentration (MIC) test by using broth microdilution method. Presence of class 1 integron was evaluated by the polymerase chain reaction (PCR) assay. RESULTS: Out of a total of 83 patients who were microbiologically diagnosed as VAP, 52 non-duplicated NFGNBs (24 P. aeruginosa and 28 A. baumannii) were causative of VAP, out of which MDR NFGNBs were responsible for 48 (57.83%) cases. The frequencies of MDR NFGNBs were as follows: 27 (56.25%) A. baumannii and 21 (43.75%) P. aeruginosa. P. aeruginosa isolates were resistant to all aminoglycoside antibiotics (50%), ciprofloxacin (45.8%), ceftazidime (70.8%), cefepime (87.5%), colistin (62.5%), and imipenem (29.2%). A. baumannii isolates were resistant to aminoglycosides (53.6%), ciprofloxacin (85.7%), ceftazidime (92. 9%), cefepime (92.9%), colistin (35.7%), and imipenem (57.1%). Twelve isolates were resistant to all 10 tested antibiotics. The number of rates of class 1 integron, positive for MDR P. aeruginosa and MDR A. baumannii, were 20 (95.23%) and 21 (77.78%), respectively. CONCLUSION: The high prevalence of multidrug resistance and incidence of class 1 integron is a therapeutic concern. Employing antibiotic stewardship in hospitals could prevent the dissemination of MDR bacteria.

Assessment of extended-spectrum ß-lactamases and integrons among Enterobacteriaceae in device-associated infections: multicenter study in north of Iran.

BACKGROUND: Device-associated nosocomial infections (DA-NIs), due to MDR Enterobacteriaceae, are a major threat to patient safety in ICUs. We investigated on Extended-spectrum ß-lactamases (ESBL) producing Enterobacteriaceae and incidence of integrons in these bacteria isolated from ventilator-associated pneumonia (VAP) and catheter-associated urinary tract infections (CAUTIs) in 18 governmental hospitals in the north of Iran. METHODS: In this cross-section study, the antibiotic susceptibility test was performed using the MIC method; also, phenotypically detection of ESBL-producing bacteria was carried out by the double-disk synergy (DDS) test. Presence of ESBL-related genes and integron Classes 1 and 2 was evaluated by the PCR method. RESULTS: Out of a total of 205 patients with DA-NIs, Enterobacteriaceae were responsible for (72.68%) of infections. The most common DA-NIs caused by Enterobacteriaceae were VAP (77.18%), CAUTI (19.46%), and sepsis due to VAP (3.35%). The most frequently Enterobacteriaceae were; Klebsiella pneumoniae 75 (24; 32% ESBL positive), E. coli 69 (6; 8.69% ESBL positive) and Enterobacter spp. 5 (5; 100% ESBL positive). Distribution of ESBL-related genes was as follows: bla-SHV (94.3%), bla-CTX (48.6%), bla-VEB (22.9%) and bla-GES (17.14%). The incidence rate of integron class 1 and class 2 was (82.92%) and (2.9%) respectively. Eight types of ESBL-producing bacteria were observed. CONCLUSIONS: Due to the fact that the emergence rate of ESBL Enterobacteriaceae is increasing in DA-NIs, co-incidence of different types of ESBL genes with integrons in 75-100% of strains in our study is alarming for clinicians and healthcare safety managers. Therefore, regional and local molecular level estimations of ESBLs that are agents of DA-NIs are critical for better management of empiric therapy, especially for patients in ICUs.

Role of C-reactive Protein and Tumor Necrosis Factor-Alpha in Differentiating between Ventilator-Associated Pneumonia and Systemic Inflammatory Response Syndrome without Infectious Etiology.

BACKGROUND: Differential diagnosis of systemic inflammatory response syndrome (SIRS) with or without infectious cause is critically important in terms of initiating antimicrobial agents in case of infectious etiology such as ventilator-associated pneumonia (VAP). The aim of this study was to determine the diagnostic and prognostic roles of C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) in differentiating between ventilator-associated pneumonia and SIRS without infectious etiology. MATERIALS AND METHODS: In this prospective observational study, 91 adult intensive care unit (ICU) patients were enrolled. According to established diagnostic criteria, they were classified into three groups of "non-SIRS non-VAP", "SIRS non-VAP" and "SIRS-VAP". Serum CRP and TNF-α were measured on days 1, 3 and 7 of the study and compared using repeated measures ANOVA. RESULTS: With respect to diagnosis, there was no significant difference in the values of these biomarkers between groups (P>0.05). There was no statistically significant "time trend" for C-reactive protein and TNF-α (P>0.05). Considering both group effect and Time effect, the changes were not significantly different for CRP (P= 0.86) and TNF-α (P=0.69). In contrast, the clinical score and the clinical pulmonary infection score (CPIS) ≥ 6, had 100% specificity for diagnosing VAP. With respect to prognosis, only an unchanged or decreasing TNF-α from day 1 to day 3 was marginally associated with 28-day survival. However, day 1 and day 3 acute physiology and chronic health evaluation II (APACHE II) scores were highly associated with 28-day survival. CONCLUSION: Unlike clinical scoring system including CPIS and APACHE II, TNF-α and CRP levels were not useful as diagnostic or prognostic biomarkers for differentiating between SIRS with VAP etiology and SIRS without infectious etiology.

How aminoglycosides are used in critically ill patients in a teaching hospital in North of Iran.

BACKGROUND: Resistance to antimicrobial agents including aminoglycosides (AGs) is a great concern that is mainly related to inappropriate use. Since there were not adequate data regarding how rationally AGs are being prescribed in our critically ill patients, this study was conducted to determine the main issues in the area of appropriate use of this antibiotic class. METHODS: One hundred patients who were in the intensive care units (ICUs) of Imam Khomeini Teaching Hospital from February 2012 to August 2012 were included. A data gathering form was prepared based upon the recommendations provided by Up-to-date (20.1) 2012 and Medscape 2013. All demographic characteristics and other information about time of beginning and duration of dosage, interval of administration of AGs and creatinine (Cr) level were collected. In statistical analysis, SPSS Version 16 software was used. Independent samples t-test was used to compare the quantitative and chi-square for qualitative variables. RESULTS: Sixty six (66%) of patients received gentamicin and 38% received amikacin. In 27% of patients, serum creatinine (Cr) had been checked before and after AGs administration and 4 patients had no renal function monitoring. Monitoring of serum concentration and Cr clearance estimation was not carried out for any patients. Culture and laboratory sensitivity tests were done on 17 patients and E-coli (57%) was the most common isolated organism. CONCLUSION: The results of this study revealed that majority of the hospitalized patients in the ICU and the dosage of AGs had not been adjusted to renal function.

Characterization of Multidrug Resistant Extended-Spectrum Beta-Lactamase-Producing Escherichia coli among Uropathogens of Pediatrics in North of Iran.

Escherichia coli remains as one of the most important bacteria causing infections in pediatrics and producing extended-spectrum beta-lactamases (ESBLs) making them resistant to beta-lactam antibiotics. In this study we aimed to genotype ESBL-producing E. coli isolates from pediatric patients for ESBL genes and determine their association with antimicrobial resistance. One hundred of the E. coli isolates were initially considered ESBL producing based on their MIC results. These isolates were then tested by polymerase chain reaction (PCR) for the presence or absence of CTX, TEM, SHV, GES, and VEB beta-lactamase genes. About 30.5% of isolated E. coli was ESBL-producing strain. The TEM gene was the most prevalent (49%) followed by SHV (44%), CTX (28%), VEB (8%), and GES (0%) genes. The ESBL-producing E. coli isolates were susceptible to carbapenems (66%) and amikacin (58%) and showed high resistance to cefixime (99%), colistin (82%), and ciprofloxacin (76%). In conclusion, carbapenems were the most effective antibiotics against ESBl-producing E. coli in urinary tract infection in North of Iran. The most prevalent gene is the TEM-type, but the other resistant genes and their antimicrobial resistance are on the rise.

Determination of antibiotics consumption in buali-sina pediatric hospital, sari 2010-2011.

The increasing prevalence of antibiotic-resistant bacteria is a major health-care problem worldwide. WHO recommends DID (daily defined dose per 100 Inhabitant per day) as a standard tool for measurement of antibiotic consumption. Since there was not any information regarding the antibiotics usage pattern in the north of Iran, the aim of this study was determine this in our centre. This cross-sectional study was performed in Buali Sina hospital. Using the health information system (HIS) database, records of patients hospitalized during 22 Sep 2010 - 21 Sep 2011. Data of different wards including Neonatal, NICU, PICU, Pediatrics and Pediatric surgery were separately extracted and analyzed. Drug consumption data were expressed as DID. SPSS 16 software was used for statistical analysis. Independent samples t-test was used to compare the quantitative variables. A total of 4619 in-patients records during 1 year of study including 2494 patients in fall and winter and 2125 patients in spring and summer were evaluated. The most hospitalized patients were in Pediatric ward (43.9 %). The highest DID value were obtained for ceftriaxone (21.7), ampicillin (6.05) and vancomycin (4.7), while the lowest value was for gentamicin (0.01). In both cold and warm seasons, Ceftriaxone was the most frequent prescribed antibiotic. The rate of antibiotics consumption especially Ceftriaxone in our setting was significantly higher than the other centers. Strategies for more justified administration of antibiotics especially broad -spectrum ones are necessary.