Background We designed this single-centre clinical trial to assess the potential benefits of N-Acetylcysteine (NAC) in patients with COVID19-associated acute respiratory distress syndrome (ARDS). Methods Ninety-two patients with mild-to-moderate COVID19-associated ARDS were allocated to the placebo (45-cases) or NAC groups (47-cases). Besides standard-of-care treatment, the patients received either intravenous NAC at a dose of 40 mg/kg/day or the placebo for three consecutive days. The efficacy outcomes were overall mortality over 28-day, clinical status on day 28, based on the WHO Master Protocol, the proportion of patients requiring mechanical ventilation, changes in ARDS-severity (based on the PaO 2 /FiO 2 ratio), and Sequential Organ Failure Assessment (SOFA) scores 48 and 96 h after intervention, Results No differences were found in the 28-day mortality rate between the two groups (25.5% vs. 31.1% in the NAC and placebo groups, respectively). Although the distribution of the clinical status at day 28 shifted towards better outcomes in the NAC-treated group, it did not reach a statistical significance level (p value = 0.83). Similar results were achieved in terms of the proportion of patients who required invasive ventilator support (38.3% vs. 44.4%), the number of ventilator-free days (17.4 vs. 16.6), and median time of ICU and hospital stay. Results regarding the change in PaO 2 /FiO 2 ratio and SOFA scores also showed no significant differences between the groups. Conclusions Our pilot study did not support the potential benefits of intravenous NAC in treating patients with COVID-19-associated ARDS. More studies are needed to determine which COVID-19 patients benefit from the NAC administration. Trial registration The trial was registered at Clinicaltrials.gov (identifier code: IRCT20120215009014N355). Registration date: 2020-05-18.

BackgroundTraumatic brain injury (TBI) is one of the important causes of morbidity and mortality throughout the world, especially in young people. In recent years normobaric hyperoxia has become an important and useful step for recovery and improvement of outcome in TBI.ObjectivesThe purpose of this study was to evaluate the effects of normobaric hyperoxia on clinical neurological outcomes of patients with severe traumatic brain injuries. We used the Glasgow outcome scale (GOS), barthel index, and modified rankin scale (mRS) to measure the outcomes of patients with TBI.Patients and MethodsSixty-eight consecutive patients with severe TBI (mean Glasgow coma scale [GCS] score: 7.4) who met the inclusion criteria were entered in this randomized controlled clinical trial. The patients were randomized into two groups, as follows: 1) experimental: received 80% oxygen via mechanical ventilator in the first 6 hours of admission, 2) control: received 50% oxygen by mechanical ventilator in the first 6 hours of admission and then standard medical care. We measured the GOS, Barthel Index, and mRS at the time of discharge from hospital and reassessed these measurements at the 6-month follow-up after injury.ResultsAccording to our study, there were no significant sex or age differences between the two groups (P = 0.595 and 0.074). The number of days in the intensive care unit (ICU) in the control group and experimental group were 11.4 and 9.4 days, respectively (P = 0.28), while the numbers of days of general ward admission were 13.9 and 11.4 days (P = 0.137) respectively. The status of GOS at time of discharge were severe = 13 and 10, moderate = 16 and 19, and low = 5 and 5 in the control and experimental groups, respectively (P = 0.723); 6 months after injury, the scores were as follows: moderate = 16 and 9, low = 15 and 25, and severe = 3 and 0 (P = 0.024). The Barthel index scores in the control and experimental groups were 59.7 and 63.9 at time of discharge (P = 0.369) and 82.7 and 91.3 at 6 months after injury (P = 0.018), respectively. The mRS results were 2.6 and 2.3 at time of discharge (P = 0.320) and 1.6 and 0.7 at 6 months after injury (P = 0.006) for the control and experimental groups, respectively.ConclusionsAccording to the results of this study, oxygen therapy by mechanical ventilator in the first 6 hours after injury in patients with severe TBI can improve the final GOS, Barthel index, and mRS scores. It could also improve long-term outcomes and enhance rehabilitation and the quality of life.

PurposeIn critically ill patients, monitoring free phenytoin concentration is a valuable method for phenytoin-dosage adjustment. However, due to technical difficulties and the high cost of these methods, the Sheiner–Tozer equation is routinely used for estimating free phenytoin concentration in clinical practice. There have been conflicting results concerning accuracy and precision of the Sheiner–Tozer equation for prediction of free phenytoin concentration in various patient populations. Therefore, this study was conducted to evaluate the accuracy and correlation of measured and calculated free phenytoin concentrations in neurointensive care patients with hypoalbuminemia.MethodsA total of 65 adult neurointensive care patients with hypoalbuminemia who were receiving phenytoin for prevention or treatment of seizures were recruited in this study. In addition to measuring free phenytoin concentration by HPLC, free phenytoin concentration was calculated using both conventional and revised Sheiner–Tozer equations. Eventually, the correlation and level of agreement between measured and calculated free phenytoin concentrations were evaluated.ResultsThe mean albumin concentration of studied patients was 2.63±0.57 g/dL. There was a significant but weak–moderate correlation between measured and calculated free phenytoin concentration using conventional and revised Sheiner–Tozer equations (r=0.45 and r=0.43, respectively). Conventional and revised Sheiner–Tozer equations were not able to predict free phenytoin concentrations accurately in 33.85% and 35.4% of patients, respectively. Although the sex of patients did not have a significant impact on the level of agreement, younger patients had a higher level of agreement.ConclusionAlthough there was a moderate correlation between calculated and measured free phenytoin concentration, the Sheiner–Tozer equation was not able to predict free phenytoin concentration accurately in all patients, especially in older patients. Therefore, monitoring free phenytoin serum concentration besides clinical outcomes should be considered for phenytoin-dose adjustment in critically ill patients.

Background This prospective controlled clinical trial aimed to compare the efficacy of methylprednisolone, dexamethasone, and hydrocortisone at equivalent doses in patients with severe COVID-19. Methods In total, 106 patients with mild to moderate COVID-19-related acute respiratory distress syndrome (ARDS) were randomized to receive either dexamethasone (6 mg once a day), methylprednisolone (16 mg twice a day), or hydrocortisone (50 mg thrice a day) for up to 10 days. All participants received a standard of care for COVID-19. The primary and secondary efficacy outcomes included all-cause 28-day mortality, clinical status on day 28 assessed using the World Health Organization (WHO) eight-category ordinal clinical scale, number of patients requiring mechanical ventilation and intensive care unit (ICU) care, number of ventilator-free days, length of hospital and ICU stay, change in PaO 2 :FiO 2 ratios during the first 5 days after treatment, and incidence of serious adverse events. P -values below 0.008 based on Bonferroni’s multiple-testing correction method were considered statistically significant. Results According to the obtained results, there was a trend toward more favorable clinical outcomes in terms of needing mechanical ventilation and ICU care, number of ventilator-free days, change in PaO 2 :FiO 2 ratios during the first 5 days after treatment, clinical status score at day 28, length of ICU and hospital stay, and overall 28-day mortality in patients receiving dexamethasone compared to those receiving methylprednisolone or hydrocortisone; however, likely due to the study’s small sample size, the difference between groups reached a significant level only in the case of clinical status score on day 28 ( p -value = 0.003). There was no significant difference in the incidence of serious adverse events between the study groups. Conclusion Based on the results, severe cases of COVID-19 treated with dexamethasone might have a better clinical status at 28-day follow-up compared to methylprednisolone and hydrocortisone at an equivalent dose. Larger multicenter trials are required to confirm our findings.

Seventy-nine cleft lip and/or palate births were isolated from 21,138 live births between January 1, 1983 and December 31, 1988 in one hospital in Tehran. Among these, 21 (26.58 percent) were cleft lip (CL), 45 (56.96 percent) were cleft lip and palate (CLP), and 13(16.45 percent) were cleft palate (CP). Chemical sulfur mustard gas was indicated as a major factor in 30 (37.97 percent) of the bilateral cleft lip and palate infants.