Efficacy and safety of Tocilizumab, plasmapheresis and their combination in severe COVID-19: A randomized clinical trial.

BACKGROUND: This study sought to evaluate and compare the effectiveness of plasmapheresis, Tocilizumab, and Tocilizumab with plasmapheresis treatment on the removal of inflammatory cytokines and improvement clinically of patients with severe COVID-19 in Intensive Care Units (ICU) due to the association between increased cytokine release and the severity of COVID-19. METHODS: This clinical trial study was conducted in three treatment arms in Iran. All patients received standard care and randomization into one of three treatment groups; Tocilizumab (TCZ) alone, plasmapheresis alone, or a combination of Tocilizumab and plasmapheresis. Demographics, clinical evaluation, oxygenation status, laboratory tests and imaging data were evaluated in the three groups and re-checked 48 h after the end of treatment trials. Primary outcomes were oxygenation status, the need for mechanical ventilation and the rate of death. RESULTS: Ninety-four patients were included in the trial after meeting the eligibility requirements. Twenty-eight patients received Tocilizumab alone, 33 had plasmapheresis alone, and 33 received both Tocilizumab and plasmapheresis. Baseline characteristics did not differ between three groups that included demographic, clinical and laboratory parameters. Following therapy, there was no difference between the three groups for CRP, ferritin, d-dimer, IL-6, pro-calcitonin and neutrophil to lymphocyte ratio (NLR) (P > 0.05). While a significant reduction was found in CRP levels within each group (32.04 ± 42.43 to 17.40 ± 38.11, 51.28 ± 40.96 to 26.36 ± 33.07 and 41.20 ± 34.27 to 21.56 ± 24.96 in the tocilizumab, plasmapheresis, and combined group, respectively) (p < 0.05), procalcitonin levels were elevated significantly in the Tocilizumab group (0.28 ± 0.09 to 0.37 ± 0.11) (p < 0.05). Clinically there was no difference between the three groups following treatment for O2 saturation levels with supplementary oxygen at discharge, endotracheal intubation rate, use of NIVPP, mortality, mean hospital and ICU length of stay (p > 0.05). CONCLUSION: Study results showed that the reduction of serum inflammatory markers, the rate of intubation and therapeutic complications including death were no different between the three groups; however, CRP levels were significantly reduced in all three groups, indicating that the interventions reduced inflammation likely through a reduction in the cytokine storm, though clinical outcomes were unaffected.

Behavioural changes in medication safety: Consequent to an action research intervention.

AIM: To explore the extent to which action research assists developing medication safety behaviours among emergency medicine staff. BACKGROUND: Health care staff involved in medication therapy are frequently required to implement progressive changes. To permanently improve medication safety, we must consider staff behaviour. This study utilizes action research to engage health care workers and engender behavioural changes. METHOD: Two cycles of action research were implemented. Data were collected through pre- and post-medication safety surveys, unstructured interviews and field notes. Staff in the emergency department worked together to progress the study cycles. RESULTS: The pre-evaluation phase revealed deficiencies in staff medication safety behaviour. Subsequent to the implementation of safety initiatives, pre- to post-evaluation comparison indicated significant improvement in medication safety behaviours. In response to qualitative reflection phase data in reflection, ward pharmacists were placed in the emergency department and anew policy on responding to medication error was developed. Analysed field notes revealed improved safe patient care, enhanced pharmaceutical knowledge and changes in the emergency department climate. CONCLUSIONS: Through action research, this study introduced actions to improve medication safety behaviours in the emergency department. Staff involvement led to changed safety behaviours. IMPLICATION FOR NURSING MANAGEMENT: This study advises nurse managers of the benefit of pharmacist-led medication therapy, interprofessional medication safety courses and active communication between front-line staff and managers regarding medication safety.

The effect of intravenous tranexamic acid on preventing the progress of cerebral hemorrhage in patients with brain traumatic injuries compared to placebo: A randomized clinical trial.

Background: Head trauma is one of the common reasons for patient attendance in the emergency ward. This study investigated the effect of tranexamic acid as a cheap, easily available antifibrinolytic drug on reducing the progress of cerebral hemorrhage compared to placebo. Methods: This double-blind controlled clinical trial was performed on 120 traumatized patients presenting to the emergency room of Shahid Rahnemoon hospital during 2014-2015, Yazd, Iran. Those patients who met the inclusion criteria were randomly allocated into 2 groups. Group A received tranexamic acid, while group B received placebo parenterally. Finally, 56 patients in Group A and 44 in Group B were analyzed. The patients underwent brain CT scan and were followed up for ICU stay in days. Also, the number of patients who died during the first 7 days of hospitalization was recorded. The data were analyzed with SPSS20 using independent samples t test and chi-square test. Results: The mean age of the patients was 41±20.27 years. Also, 20 patients (20%) were female and 80 were male (80%). There was no significant difference between the drug group and placebo group in the rate of hemorrhage volume progress (p=0.824). Regarding patients' ICU stay, the ICU stay of the tranexamic acid group decreased significantly compared to the placebo group (p=0.001). No significant difference was found between the intervention group and placebo group in the mortality rate of patients during the first 7 days of hospitalization (p=0.236). Conclusion: Tranexamic acid has no effect on reducing cerebral hemorrhage volume in patients. Although this drug was not effective in reducing mortality rate in patients, it decreased their ICU stay.

Identification and Prioritization of Key Components Influencing Prehospital Emergency Related to Preventable Road Traffic Injuries Deaths in Iran; A Delphi Study.

OBJECTIVE: To identify and prioritize the key Components of prehospital emergency system to prevent mortality in road traffic injuries. METHODS: A total of 25 emergency medicine practitioners, emergency ward nurses, and managers of prehospital emergency centers participated in this adjusted Delphi study in three rounds. After extracting the primary components through reviewing systematic studies and interviewing experts, the Delphi rounds were performed with the presence of experts. The data were analyzed with both qualitative content analysis and quantitative analysis using SPSS20 software. For the analysis and selection of the final priorities, the coefficient of agreement of over 70% was used. RESULTS: After doing three Delphi rounds, in the final Delphi round, 10 superior components were selected respectively as follows: correct history taking of the victim, examining possible cervical injury, the time spent from the first call to arrival of technicians to the scene, the time spent from arriving at the scene to the time of hospital transport, passing of re-education courses by EMS technicians, coordination among the rescue organizations, police, the Red Crescent, fire station, and healthcare organizations, integrated commandership at scene, police attendance in the scene before EMS arrival at the scene, proper ambulance equipment with respect to the required equipment (A, B, C) on the basis of victim's condition, and coordination with the target hospital for patient transport. CONCLUSION: This study determined the most applicable managerial methods of prehospital emergency components pertaining to preventable fatal road traffic injuries through empowerment of EMS systems in the fields of victim assessment, time management indices, personnel training, coordination between the involved organs, and the presence of the main commander in the scene.

Management of Preventable Deaths due to Road Traffic Injuries in Prehospital Phase; a Qualitative Study.

INTRODUCTION: Prehospital care plays an important role in decreasing the number of deaths due to road traffic injuries (RTIs). This study aimed to identify the challenges of preventable deaths due to RTIs in the prehospital phase based on the attitudes of stakeholders. METHODS: Conventional content analysis of qualitative study was used to analyze the data. The participants were 24 RTI prevention experts from fire-fighting organization, traffic police, the Red Crescent, Emergency Medical Services staff, emergency medicine specialists, and hospital emergency nurses who were selected by means of purposive sampling. Data were collected using unstructured interviews and analyzed by means of data coding, followed by extracting sub-categories, and main categories. RESULTS: Six main categories were extracted as the major challenges of preventable deaths in RTIs in the prehospital phase including "poor management of the crash scene" with two subcategories of lack of rapid access to the patient and lack of scene safety, "lack of adequate rules and regulations" with two subcategories of lack of protocols and guidelines and lack of clear duties checklists, "poor management of time" with two subcategories of elongated response time at the crash scene and elongated time of victim transport, "low quality of training" with two subcategories of insufficient training of Emergency Medical Services (EMS) staff and inadequate public training, "poor communication and coordination" with two subcategories of poor communication of EMS staff and lack of uniform commandership at the crash scene, and "low quality of victim management" with two subcategories of low quality of clinical care and lack of accurate clinical assessment. CONCLUSION: The following measures are necessary to reduce preventable deaths due to RTIs in the prehospital phase: accurate clinical assessment of the victim on the scene, provision of high quality and accurate clinical care, enforcement of legal obligations and using protocols in the field of victim management, coordination of the involved organizations through identifying the duties and responsibilities of each organization, and full management of the crash scene by assigning a unique commander to each unit and creation of the highest level of safety on crash scene.

Intravenous Haloperidol versus Midazolam in Management of Conversion Disorder; a Randomized Clinical Trial.

INTRODUCTION: Conversion disorder is a condition in which the patient shows psychological stress in physical ways. This study aimed to compare the effects of haloperidol versus midazolam in patients with conversion disorder. METHODS: This double-blind randomized clinical trial was conducted on patients with conversion disorder who had presented to the emergency department, throughout 2015. Patients were randomly divided into two groups and were either treated with 2.5 mg of intravenous (IV) haloperidol or 2.5 mg of IV midazolam. Recovery rate, time to recovery, and side effects of both drugs 1 hour, 24 hours, and 1 week after treatment were compared using SPSS19. RESULTS: 140 patients were divided into two groups of 70. There were no significant differences between the groups regarding the baseline characteristics. 12 (17.1%) patients who were treated with IV haloperidol experienced drug side effects within 1 hour and 12 (17.1%) within 24 hours, while only 3 (4.3%) patients in IV midazolam experienced side-effects within 1 hour after drug administration (p = 0.026). The symptoms of the disease subsided in 45 (success rate: 64.3%) patients in midazolam and in 64 (success rate: 91.5%) participants in haloperidol group (P<0.001). Mean recovery time was 31.24 ± 7.03 minutes in IV midazolam and 30.53 ± 7.11 minutes in IV haloperidol group (p = 0.592). Absolute risk reduction (ARR) of treating patients with haloperidol compared to midazolam is about 27%. CONCLUSION: The response of patients to treatment with haloperidol is clearly better than midazolam. Although more transient and minor side-effects were observed in the group treated with haloperidol compared to midazolam group, serious side-effects were rare for both treatments.

Intravenous versus Subcutaneous Midazolam Using Jet-injector in Pediatric Sedation; a Randomized Clinical Trial.

INTRODUCTION: The quality of interventions in children is largely dependent on their control. Hence, this study compared the sedative effects of subcutaneous (SC) and intravenous (IV) Midazolam in pediatric sedation induction. METHODS: This randomized clinical trial was conducted on children aged 1-6 years presenting to emergency departments of Shahid Sadoughi and Shahid Rahnemoon Hospitals, Yazd, Iran. Participants were randomly assigned to IV or SC midazolam using a jet injector and success rate, degree of sedation, and satisfaction of parents and physician were compared between groups. RESULTS: 60 cases with the mean age of 3.15±1.43 (1-6) years were randomly assigned to the SC (30 cases) or IV (30 cases) groups (56.7% female). SC and IV groups were similar regarding the mean age (p = 0.165) and sex (p = 0.121). Depth of sedation (p=0.900), control of child (p=0.711), in-charge physician's satisfaction (p=0.467), successful sedation and need for rescue dose (p=0.519) were not different between groups. IV midazolam group had a significantly shorter recovery time (about 10 minutes; p=0.040) and SC midazolam group had a significantly higher level of parent satisfaction (p=0.001). CONCLUSION: The findings indicate no significant difference in depth of sedation, control of child, in-charge physician's satisfaction, successful sedation (reaching stage 1 of sedation or higher), and need for rescue dose of SC and IV midazolam. Parents' satisfaction was significantly greater with SC administration and IV injection had shorter recovery time.

The Effect of Hyoscine on Pain, Tenderness, and Rebound Tenderness in Patients with Appendicitis: Quasi-Interventional Study.

OBJECTIVE: To evaluate the effect of hyoscine on pain and tenderness, rebound tenderness and appendicitis patients before surgery and this study can be considered as the first study investigated the efficacy of hyoscine on pain, tenderness, and rebound tenderness in patients with appendicitis. METHODS: In this single-group, prospective interventional study (before-after) according to inclusion and exclusion criteria, 70 patients with pain in the right lower abdomen and typical symptoms of appendicitis were evaluated and after surgery, diagnostic accuracy was examined by pathologic results. The pain was evaluated before and after administration of hyoscine by numerical and verbal examination. Tenderness and rebound tenderness were also determined. RESULTS: The mean age of patients was 26.81±7.66. Totally, 42 patients (60%) had reduction in pain, 50 patients (71% percent) had reduction in tenderness, and 39 (55%) had reduction in rebound tenderness after treatment with the drug. A statistically significant reduction of pain and tenderness, rebound tenderness was observed in all of men after administration of hyoscine (p<0.001) but in women, the reduction of severity of tender results was only significant (p=0.002). Data analysis in women and men together showed the significant reduction of pain, tenderness, and rebound tenderness (p<0.001). CONCLUSION: According to the results, hyoscine can reduce pain, tenderness, and rebound tenderness. So, it seems that hyoscine is a good candidate for patients with appendicitis. IRCT REGISTRATION NUMBER: IRCT2015111825123N1.

Acute necrotizing pancreatitis following coronary artery angiography: A case report.

BACKGROUND: Acute pancreatitis has different etiologies from biliary stone to metabolic disturbances. Coronary angiography is one of the newly understood etiologies. CASE REPORT: This paper is about a women suffering from acute pancreatitis after coronary angiography. CONCLUSION: Embolization of cholesterol crystals due to vessel wall trauma during coronary angiography as well as contrast medium are responsible for such side effect.

Comparison of local anesthetic effect of lidocaine by jet injection vs needle infiltration in lumbar puncture.

BACKGROUND: Usual routes of drug administration are often painful and invasive. Nowadays, using jet injection has been introduced successfully, as a noninvasive and painless method of anesthetic delivery in performing different procedures. OBJECTIVE: The objective of the study is to compare the local anesthetic effect of lidocaine by jet injection vs needle infiltration in performing lumbar puncture in the emergency department (ED). METHODS: A randomized single-blind controlled study was performed in 65 patients needing lumbar puncture recruited from the ED from July to November 2014. We enrolled 44 patients and excluded 21 patients by the exclusion criteria. Local lidocaine was delivered in 1 group by jet injector (group B), whereas in the other group conventional method, needle infiltration was used (group A). In both groups, intravenous midazolam 1 mg was administered as an anxiolytic drug before the procedure. Patients' pain score (visual analog scale [VAS]) from 0 to 10 was recorded both during drug delivery and performing the procedure itself. The observer who collected patients' data and fulfill the questionnaire was blinded to the study. RESULTS: During lidocaine injection, the mean ± SD VAS score was 5.27 ± 1.77 in group A and 2.95 ± 1.81 in group B (mean difference, 2.31; 95% confidence interval, 1.22-3.41) (P= .000). During performing the procedure, the mean ± SD VAS score in groups A and B was 3.77 ± 1.77 vs 2.18 ± 1.50 (mean difference, 1.59; 95% confidence interval, 0.59-2.58) (P= .003). CONCLUSIONS: Injecting lidocaine by jet injector is less painful than infiltrating it by needle and syringe.

Analgesic effect of paracetamol combined with low-dose morphine versus morphine alone on patients with biliary colic: a double blind, randomized controlled trial.

BACKGROUND: Numerous drugs have been proposed to alleviate pain in patients with biliary colic, especially opioids, but still there is a tendency to use less narcotics because of their side effects and the unwillingness of some patients. The present study aimed to compare the analgesic effect of paracetamol combined with low-dose morphine versus morphine alone in patients with biliary colic. METHODS: A randomized double-blind controlled trial was performed in 98 patients with biliary colic, recruited from two emergency departments from August 2012 to August 2013. Eleven patients were excluded and the remaining were randomized into two groups: group A received 0.05 mg/kg morphine+1 000 mg paracetamol in 100 mL normal saline and group B received 0.1 mg/kg morphine+normal saline (100 mL) as placebo. Pain scores were recorded using visual analogue scale (VAS) at baseline and 15 and 30 minutes after drug administration. Adverse effects and the need for rescue medication (0.75 µg/kg intravenous fentanyl) were also reported within 60 minutes of drug administration. RESULTS: Before the infusion, the mean±SD VAS scores were 8.73±1.57 in group A and 8.53±1.99 in group B. At 15 minutes after drug administration, the mean±SD VAS scores were 2.16±1.90 in group A vs. 2.51±1.86 in group B; mean difference was -0.35, and 95%CI -1.15 to 0.45 (P=0.38). At 30 minutes the mean±SD VAS scores were 1.66±1.59 in group A vs. 2.14±1.79 in group B; mean difference was -0.48, and 95%CI -1.20 to 0.24 (P=0.19). The mean pain scores in the two groups at 15 and 30 minutes demonstrated no significant difference. CONCLUSION: Paracetamol combined with low-dose morphine may be effective for pain management in patients with biliary colic.

Naproxen Twice Daily Versus as Needed (PRN) Dosing: Efficacy and Tolerability for Treatment of Acute Ankle Sprain, a Randomized Clinical Trial.

PURPOSE: This study was conducted to compare the efficacy and safety of naproxen 500 mg twice daily (BID) versus naproxen 500 mg as needed (PRN) for treatment of ankle sprain. METHODS: In this seven-day, randomized, parallel group trial, 135 patients with ankle sprain occurring less than 48 hours prior to the first dose of study medication were randomized to receive naproxen 500 mg BID (67 patients) and naproxen 500 mg as needed (PRN) (68 patients). The ankle pain was assessed at rest and on full weight bearing using Numeric Rating Scale (NRS) from 0 (no pain) to 10 (the worst imaginable pain). Ankle swelling was assessed as a 4-point scale ranging from 0 (no swelling) to 3 (severe swelling) rated by the investigator. The primary efficacy end point was the patient's assessment of ankle pain via NRS and the degree of swelling on day seven. RESULTS: Results showed a significant decrease in pain on weight bearing, pain at rest and the extent of swelling (P<0.001) in both groups, but there was no substantial difference between the two groups (P>0.05) after seven days. Assessing the safety profile of the two different dosing, 13.3% of the naproxen BID group and 6.7% of the as needed group had adverse events, showing that the as needed regimen was safer (P<0.001). CONCLUSION: Results showed that naproxen as needed may reduce the pain and edema of the sprained ankle with no significant difference compared to the BID regimen, while it possesses better safety profile and lower total drug use.