Thromboprophylaxis for Coagulopathy Related to COVID-19 in Pediatrics: A Narrative Review.

In addition to harming the respiratory system, COVID-19 can affect multiple organs. Children may develop a specific complication of COVID-19 called multisystem inflammatory syndrome in children (MIS-C) which could influence the vascular system of children and cause multiple coagulopathies in the body. Information on the use of thromboprophylaxis in this condition was collected via the review of various articles. In general, different factors in immune system responses can trigger the initiation of thrombotic events. Studies have shown that starting anticoagulant prophylaxis, which contributes to decreased thrombotic events, is dependent on the patient's condition and D-dimer levels. However, further studies on pediatric populations are needed to establish the role of anticoagulants in children with this condition.

Current evidence on the use of anakinra in COVID-19.

Despite the progressing knowledge in COVID-19 management, remdesivir is the only agent that got approval to inhibit viral replication. However, there are limited data about effective immunomodulatory agents to prevent cytokine release in COVID-19. Cytokine release syndrome in COVID-19 resembles secondary hemophagocytic lymphohistiocytosis, in which interleukin-1 (IL-1) plays a key role. Anakinra is the first recombinant IL-1 receptor antagonist studied for off-label use in COVID-19 treatment. This study reviews the current clinical evidence on the role of interleukin-1 in COVID-19-related cytokine storm, therapeutic effects, significant clinical concerns, and pros and cons of anakinra administration in the management of COVID-19 patients. In this review, four items are shown to be important for achieving the optimal therapeutic effects of anakinra in COVID-19 patients. These items include duration of treatment ≥ 10 days, doses ≥ 100 mg, intravenous administration, and early initiation of therapy. Also, anakinra might be more beneficial in the early stages of the disease when higher levels of cytokines are yet to be observed, which could prevent progression to severe illness and mechanical ventilation. Further studies are required to address the SARS-CoV-2 induced cytokine release syndrome and the role of anakinra in identifying ideal treatment approaches for COVID-19 patients based on their clinical status.

The effects of a combination oral spray (Mucosamin®) for the prevention of oral mucositis in pediatric patients undergoing hematopoietic stem cell transplantation: a double blind randomized clinical trial.

PURPOSE: Oral mucositis (OM) is a frequent complication of conditioning regimens for hematopoietic stem cell transplantation (HSCT). Damage to the nuclear and non-nuclear materials of the mucosal cells by the production of Reactive Oxygen Species (ROS) and proinflammatory cytokines could result to development and progression of OM. Previous studies have shown the effectiveness of Mucosamin® oral spray in the management of pain and acceleration of OM healing. The aims of the current study were to evaluate prophylactic effects of Mucosamin® oral spray in reducing the incidence and severity of OM in pediatric patients undergoing allogeneic HSCT. METHOD: The current study was designed as a double-blind, placebo-controlled randomized clinical trial. Sixty patients were enrolled in the study and received placebo or Mucosamin® spray. Patients in both groups used sprays 4 times daily. Product application was begun at the time of initiation of conditioning regimen and was continued for 14 days. RESULTS: Mucosamin® significantly reduced incidence and severity of OM compared to the placebo (P values: 0.027 and 0.035, respectively). This product could also decrease OM duration and delay OM onset (P values: 0.007 and 0.006, respectively). CONCLUSION: Mucosamin® could effectively reduce incidence, severity, and duration of OM and delay OM onset in pediatric patients undergoing allogeneic HSCT. TRIAL REGISTRATION: The study protocol was registered in the Iranian Registry of Clinical Trials under the registry number IRCT20190917044805N1.

Vancomycin pharmacokinetic parameters in patients undergoing hematopoietic stem cell transplantation.

INTRODUCTION: Current guidelines on vancomycin dosing lack specific recommendations about its dosing in hematopoietic stem cell transplant (HSCT) patients, the objective of the current study was to compare vancomycin pharmacokinetic variables in this population with those of general population. METHODS: A prospective study was designed and the calculated parameters of vancomycin pharmacokinetic were compared with individualized parameters. Two trough levels before 4th and 5th doses and a peak level after the 4th dose, were taken. All patients received a dose of 15 mg/kg of vancomycin two or three times a day. Pharmacokinetic parameters were calculated using a one compartmental model. The association between different variables and of acute kidney injury (AKI) development and achievement of target levels were also evaluated. RESULTS: A significant difference was observed between population Volume of distribution (Vd) and individualized Vd (mean 57.33 L vs 162.86 L, p value 0.019) and trough and peak levels (p values 0.0001 and 0.001; for mean trough and peak levels respectively). The achievement of the recommended trough levels and area under the concentration time curve per minimum inhibitory concentration (AUC24/MIC) was very low (5/71 and 24/71 patients respectively). No significant differences were observed between population and individualized clearance and rate of elimination of vancomycin (p values of 0.092 and 0.55 respectively). Concomitant receipt of cyclosporine was significantly related with development of AKI (p value 0.046). CONCLUSION: The dosing methods which use population-based pharmacokinetic variables does not result in desired therapeutic levels in HSCT patients, mainly because of larger vancomycin volume of distribution.

Predictors of the prolonged recovery period in COVID-19 patients: a cross-sectional study.

BACKGROUND: The clinical course of COVID-19 may vary significantly. The presence of comorbidities prolongs the recovery time. The recovery in patients with mild-to-moderate symptoms might take 10 days, while in those with a critical illness or immunocompromised status could take 15 days. Considering the lack of data about predictors that could affect the recovery time, we conducted this study to identify them. METHODS: This cross-sectional study was implemented in the COVID-19 clinic of a teaching and referral university hospital in Tehran. Patients with the highly suggestive symptoms who had computed tomography (CT) imaging results with typical findings of COVID-19 or positive results of reverse transcriptase-polymerase chain reaction (RT-PCR) were enrolled in the study. Inpatient and outpatient COVID-19 participants were followed up by regular visits or phone calls, and the recovery period was recorded. RESULTS: A total of 478 patients were enrolled. The mean age of patients was 54.11 ± 5.65 years, and 44.2% were female. The median time to recovery was 13.5 days (IQR: 9). Although in the bivariate analysis, multiple factors, including hypertension, fever, diabetes mellitus, gender, and admission location, significantly contributed to prolonging the recovery period, in multivariate analysis, only dyspnea had a significant association with this variable (p = 0.02, the adjusted OR of 2.05; 95% CI 1.12-3.75). CONCLUSION: This study supports that dyspnea is a predictor of recovery time. It seems like optimal management of the comorbidities plays the most crucial role in recovery from COVID-19.

Is Inhaler Technique Associated with Quality of Life in Patients with Chronic Obstructive Pulmonary Disease?

BACKGROUND: Inhalers are the mainstay of treatment for patients suffering from chronic obstructive pulmonary disease. However, incorrect inhaler technique is a considerable challenge. OBJECTIVE: We aimed to evaluate inhaler technique and its association with quality of life in a sample of patients with chronic obstructive pulmonary disease. METHODS: This cross-sectional study included patients with confirmed chronic obstructive pulmonary disease who were prescribed at least 1 inhaler medication on a regular basis. Patients were recruited from the outpatient pulmonary clinic of a hospital in Tehran. Inhaler technique was assessed according to a validated checklist. Patients' quality of life was evaluated using Chronic Obstructive Pulmonary Disease Assessment Test. RESULTS: One hundred seventy-five patients with mean (SD) age of 59.0 (10.1) years were included. Patients' devices were 192 (62.3%) pressurized metered-dose inhalers (including pressurized metered-dose inhalers plus spacer) and 116 (37.7%) dry powder inhalers. Unfortunately, only 2.86% of patients used their inhalers completely correct. The highest rate of errors was committed by patients who used metered-dose inhalers plus spacer. Patients with a higher educational degree had significantly lower rate of errors on average (P = 0.001). The most frequent errors made by patients using pressurized metered-dose inhalers or Turbuhaler was priming the inhaler before the first administration in 90.6% and 78.3% of patients, respectively. Chronic Obstructive Pulmonary Disease Assessment Test scores in patients using different inhaler devices were not significantly different. However, in patients with lower quality of life, significantly more patients had poor inhaler technique (P = 0.0001). CONCLUSIONS: There is still considerable need for interventions to optimize inhaler technique. We also noted that appropriate inhaler technique is associated with better quality of life. (Curr Ther Res Clin Exp. 2020; 81:XXX-XXX).

Acute cerebellar toxicity induced by high dose of cytarabine (HiDAC): A case report.

Cytarabine is a pyrimidine analogue that is used for the treatment of acute myeloid leukemia at different doses. Standard doses of cytarabine are used for induction therapy, while high doses are used for post-remission (consolidation) and relapsed/refractory treatment. One of the major side effects of its high doses is acute cerebellar toxicity occurring in 10 to 25% of patients. We report a case that developed this side effect after receiving two doses of high-dose cytarabine. The patient's symptoms improved after withholding the drug. Thereafter, the patient tolerated treatment continuation with lower doses.

Successful desensitization of a patient with cetuximab hypersensitivity: A case report.

BACKGROUND: Severe hypersensitivity reaction is a dangerous adverse drug reaction in patients receiving cetuximab. It requires drug discontinuation and medical management. CASE DESCRIPTION: A 48-year-old man, previously diagnosed with metastatic colorectal cancer, was admitted for therapy continuation. During the first infusion of cetuximab, the patient experienced acute signs of hypersensitivity reactions. The treatment team decided to administer cetuximab employing the desensitization protocol. CONCLUSIONS: This study reports a severe hypersensitivity reaction to cetuximab in an adult patient with colorectal cancer. This patient was successfully managed with a new safe and rapid desensitization protocol.

Comparison of Efficacy and Safety of Two Different Enoxaparin Products in Prevention of Venous Thromboembolism Following Major Obstetric-gynecological Surgeries: An Open-label Randomized Clinical Trial.

Venous thromboembolism (VTE) occurs in about 5 percent of patients undergoing major abdominal surgeries. Prophylaxis of VTE is recommended using unfractionated heparin (UF) or low molecular weight heparin (LMWH) in high-risk patients. In spite of advantages and confirmed cost-effectiveness of LMWH, high costs of enoxaparin branded preparations limit its use. We aimed to compare the efficacy and safety of two enoxaparin preparations. In this open-label randomized clinical trial, 200 patients were recruited to recieve PDxane® or Clexane®, 40 mg subcutaneously daily, from the day of surgery for 10 days. The patients were evaluated for VTE occurrence and side effects considering clinical and laboratory examinations at the beginning and day 10. No cases of proximal or distal VTE or life threatening bleeding were observed among 102 and 98 patients who received PDxane® and Clexane®, respectively. The adverse effects observed in PDxane® and Clexane® groups included injection site reactions (rash: P = 0.97; pain: P = 0.55 and erythema: P = 0.33), anemia (P = 0.32), hematuria (P = 0.16), confusion (P = 0.3), and increased liver transaminases (AST ≥ 3 × ULN: P = 0.16 and ALT ≥ 3 × ULN: P = 0.66). In according to the study results PDxane® was of similar efficacy and safety compared to Clexane® in preventing VTE following major obstetric-gynecological surgeries. Considering lower cost of PDxane®, it could be a safe and effective alternate for VTE prophylaxis in the patients undergoing such types of surgeries.

Comparison of the Effects of Melatonin and Oxazepam on Anxiety Levels and Sleep Quality in Patients With ST-Segment-Elevation Myocardial Infarction Following Primary Percutaneous Coronary Intervention: A Randomized Clinical Trial.

BACKGROUND: Anxiety and sleep disorders are prevalent problems in patients presenting with ST-segment-elevation myocardial infarction (STEMI). Usually, these problems are managed by benzodiazepines, which-albeit effective-could cause adverse effects and drug interaction. OBJECTIVE: This study was designed to compare the effects of melatonin and oxazepam in the management of anxiety and insomnia on patients following primary percutaneous coronary intervention (PCI) with a view to providing a safer alternative. METHODS: This study was designed as a randomized clinical trial. STEMI patients managed with primary PCI were enrolled and randomized into 2 groups through the permuted block randomization. The patients received either oxazepam (10 mg) or melatonin (3 mg) every night. Autoimmune disease or previous use of psychoactive medications was considered the exclusion criterion. Levels of anxiety and sleep quality were evaluated using the Hamilton Anxiety Rating Scale (HAM-A) and the Groningen Sleep Quality Score and compared between the groups. RESULTS: Each group contained 20 patients. Melatonin showed a significant advantage over oxazepam in improving sleep quality ( P = 0.040). Comparisons of the efficacy of both medications in lowering the anxiety levels when considering all the items of the HAM-A, including those related to cardiovascular disease, were significantly in favor of melatonin ( P = 0.019). CONCLUSIONS AND RELEVANCE: The results of this study suggest that melatonin, a drug with more favorable drug interaction and adverse effect profile, could be more effective than oxazepam in improving the sleep quality and anxiety levels of patients presenting with STEMI, and it could be considered a new alternative to benzodiazepines in this setting.

Effect of solvent type on retardation properties of diltiazem HCl form liquisolid tablets.

Liquisolid technique is a new approach to formulate sustained release dosage forms. It seems that the solubility of an active ingredient in solvent plays an important role in drug release profile. The aim of present study was to investigate the effect of solvent type on diltiazem hydrochloride release profile from liquisolid compacts. To examine aforementioned idea, the drug solubility was studied in several conventional nonvolatile solvents. Liquisolid formulations of diltiazem HCl in the different solvents were prepared and their release profiles were also obtained. Effect of aging on the hardness and drug release profile was studied as well. X-ray crystallography and differential scanning calorimetry (DSC) were used to investigate the formation of any complex between drug and carrier or any crystallinity changes during the manufacturing process. The results showed that diltiazem HCl had lowest solubility in polysorbate 20. Highest amount was devoted to polysorbate 80 and propylene glycol. Type of nonvolatile solvent and its physicochemical properties as well as solubility of the drug in the applied solvent found to have important role on release profile of the drug from liquisolid compacts. Hardness and dissolution profile of the drug were not affected by aging. Amorphous form was obtained during the process of liquisolid formulation. It follows that the optimized new technique can be used to prepare sustained release formulations of water-soluble drugs.