Adherence to practice guidelines for the management of febrile neutropenia in patients undergoing hematopoietic stem cell transplantation: An observational study in a referral center in Iran.

INTRODUCTION: Patients undergoing hematopoietic stem cell transplantation (HSCT) are suspected to develop febrile neutropenia (FN) and severe infections. Therefore, appropriate prescription of antibiotics in these patients is crucial to reduce the rates of morbidity, mortality, and antimicrobial resistance. The present study aimed to evaluate the physicians' prescription and adherence to the FN clinical guidelines among patients undergoing HSCT. METHODS: This prospective observational single-center study was conducted during a 15-month period in a tertiary referral hospital in Iran. The patients with at least one episode of FN following HSCT were included in the current study. The physicians' adherence to the Infectious Diseases Society of America (IDSA) and National Comprehensive Cancer Network (NCCN) clinical guidelines for the management of FN was evaluated using prescription data and medical record reviews. RESULTS: Two hundred and fifteen patients with 297 FN episodes were evaluated. The timing of antibiotics and the selection of the initial regimen were considered guideline-based therapy. However, antibiotic dosing and initial regimen modification were not followed in terms of the guideline recommendations in 58.1% of the patients. In particular, vancomycin was inappropriately given in 83.1% of patients. The overall adherence of physicians to the guidelines was 35.8%. CONCLUSION: Non-adherence to clinical guidelines is high particularly in initial regimen modification and administration of vancomycin, which affects hospital stay and patient's outcome. Implementation of guideline-review sessions to raise the awareness of the physicians and to improve the rational use of antimicrobial agents may be crucial.

Clinical characteristics and outcome of COVID-19 pneumonia in kidney transplant recipients in Razi hospital, Rasht, Iran.

BACKGROUND: In late December 2019, a novel coronavirus SARS-CoV-2 started to spread around the world in different populations. Its clinical and laboratory characteristics and outcome in kidney transplant recipients are little known. Therefore, we describe 22 kidney transplant recipients with SARS-CoV-2-induced pneumonia. METHODS: All kidney transplant recipients who referred to the Razi Hospital of Rasht with a diagnosis of SARS-CoV-2 infection from February 20 to 19th of April 2020 have been included in this observational study. RESULTS: We present 22 cases of COVID-19 in kidney transplant recipients (median age 52 years [interquartile range 40.75-62.75 years]) and baseline eGFR 60 (mL/min/1.73 m2 ) (44.75-86.75). Patients complained of cough (72.7%), dyspnea (63.6%), fever (68.2%), and chill (72.7%) with greater prevalence. We decreased the dose of immunosuppression and started stress dose of intravenous hydrocortisone or equivalent oral prednisolone. Each patient received antiviral therapy based on the latest updated version of local protocol at the time of admission. CT scan findings in 90.9% of patients showed bilateral multifocal lesions. Acute kidney injury (AKI) was observed in 12 patients during hospitalization. Six patients died after a median of 12 days from admission (IQR, 1-21). CONCLUSIONS: In this small observational study, we observed high AKI occurrence and mortality rate in kidney transplant recipients with COVID-19.

Successful switch to oral tacrolimus in a patient with hypersensitivity reaction to parenteral vitamin K, cyclosporine, and tacrolimus: A case report.

INTRODUCTION: Calcineurin inhibitors are widely used for the prevention and treatment of graft versus host disease in patients undergoing allogeneic hematopoietic stem cell transplantation, and successful treatment with calcineurin inhibitors is very important for the management of these cases. CASE REPORT: A 19-year-old man with thalassemia major experienced hypersensitivity reaction to parenteral vitamin K, cyclosporine, and tacrolimus before hematopoietic stem cell transplantation. All three episodes of reaction appeared a few minutes after administration of offended drugs and cause systemic signs and symptoms of anaphylaxis, i.e. itching, flushing, difficulty in breathing, and hypotension. MANAGEMENT AND OUTCOME: Hypersensitivity reaction was fully controlled by immediately discontinuing the drug and administering hydrocortisone, chlorpheniramine, epinephrine, and intravenous fluids. During hospitalization, the patient tolerated oral tacrolimus without any complication. DISCUSSION: It appears that Cremophor EL (polyoxyethylated castor oil) which acts as a carrier, solubilizer, and emulsifier in intravenous calcineurin inhibitors is responsible for the occurrence of anaphylactic reaction (anaphylaxis); therefore, it is suggested that the administration of cremophor-containing drug should be avoided in patients with a previous history of hypersensitivity reaction to one of these drugs.

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.

Significant drug interaction between voriconazole and dexamethasone: A case report.

BACKGROUND: Voriconazole is extensively metabolized by the CYP450 isoenzymes 2C19 and 3A4 and to a lesser extent by CYP2C9; therefore, any medication that affects this pathway can alter its plasma concentration. Treatment failure can probably occur if subtherapeutic levels are achieved. CASE DESCRIPTION: A 32-year-old woman who suffered from acute lymphoblastic leukemia was admitted and received treatment with vincristine and dexamethasone. After several days, to control her fever, based on two consecutive positive serum galactomannan test results, voriconazole as an antifungal agent was added to Aspergillus infection treatment. Through the first week after voriconazole initiation, its plasma concentrations were subtherapeutic. The most suspicious medication for interaction was dexamethasone, which can induce CYP450 isoenzymes and reduce plasma concentration. CONCLUSION: As a result of the narrow therapeutic window of voriconazole and the relationship between efficacy and plasma concentration of azoles, therapeutic drug monitoring of voriconazole in patients receiving a high dose of glucocorticoids is recommended, in order to achieve optimal response to treatment and toxicity reduction. Further studies regarding the interaction between voriconazole and dexamethasone to prevent clinically relevant interactions should be considered.

Nutrients in prevention, treatment, and management of viral infections; special focus on Coronavirus.

BACKGROUND: The coronavirus disease 2019 (COVID-19) is a pandemic caused by coronavirus with mild to severe respiratory symptoms. This paper aimed to investigate the effect of nutrients on the immune system and their possible roles in the prevention, treatment, and management of COVID-19 in adults. METHODS: This Systematic review was designed based on the guideline of the Preferred Reporting for Systematic Reviews (PRISMA). The articles that focussed on nutrition, immune system, viral infection, and coronaviruses were collected by searching databases for both published papers and accepted manuscripts from 1990 to 2020. Irrelevant papers and articles without English abstract were excluded from the review process. RESULTS: Some nutrients are actively involved in the proper functioning and strengthening of the human immune system against viral infections including dietary protein, omega-3 fatty acids, vitamin A, vitamin D, vitamin E, vitamin B1, vitamin B6, vitamin B12, vitamin C, iron, zinc, and selenium. Few studies were done on the effect of dietary components on prevention of COVID-19, but supplementation with these nutrients may be effective in improving the health status of patients with viral infections. CONCLUSION: Following a balanced diet and supplementation with proper nutrients may play a vital role in prevention, treatment, and management of COVID-19. However, further clinical trials are needed to confirm these findings and presenting the strong recommendations against this pandemic.

Association of Voriconazole Trough Plasma Concentration with Efficacy and Incidence of Hepatotoxicity in Iranian Patients with Hematological Malignancies.

There are conflicting data regarding the association between plasma concentration of voriconazole (VCZ) and both efficacy and safety. This study investigates the association of VCZ trough plasma level with clinical efficacy and hepatotoxicity in the Iranian population suffering hematological malignancies. This cross-sectional study was performed on adult Iranian patients (age ≥ 18 years) with hematological malignancies undergoing treatment with oral or intravenous VCZ for proven or probable invasive aspergillosis. Plasma concentrations of VCZ were measured at two time points on day 4 and 14 during the study period. A total of 60 VCZ trough concentrations of 30 patients were drawn on days 4 and 14 after the initiation of treatment. There was no definite correlation between the mean plasma concentration of VCZ and VCZ dosage (p = 0.134, r = 0.280). In multivariable model, only plasma concentration of VCZ on day 14 was associated with the incidence of hepatotoxicity (p = 0.013; OR = 1.42, 95% CI = 1.07-3.24). Plasma trough concentration neither on day 4 nor on day 14 was related to the treatment response. No significant association was observed between the mean plasma concentration of VCZ and 3-month patients' survival (p = 0.696). To conclude, VCZ trough concentration may not be a predictor of treatment response or 3-month patients' survival. However, the wide inter- and intra-patient variability of VCZ plasma concentration coupled with the observed association between VCZ trough level and the incidence of hepatotoxicity would pose the question regarding the potential benefit of VCZ concentration monitoring.

Evaluation of Medication Package Inserts in Iran.

OBJECTIVE: Package inserts (PIs) provide information for the safe and effective use of medication. There is no study on the evaluation of PIs in Iran. The purpose of this study was to evaluate the completeness of PIs supplied with the 100 top-selling medications in Iran. METHODS: This cross-sectional observational study was conducted during 3 weeks in January 2017. One hundred medications were chosen from a list supplied by the Iran Food and Drug Administration (IFDA). The PIs were assessed for the presentation and completeness of quality criteria, which was consisted of two parts. The first part was the criteria required by the IFDA, mentioned in Chapter 16 of the Pharmaceutical Regulations and Instructions provided by the IFDA. The second part of the criteria was defined according to the critical comments of clinical and industrial pharmacists. FINDINGS: Thirty-seven out of 100 medications included no PIs. None of the PIs met all the criteria required by the IFDA. The highest score for completeness was 18 out of 21 (85.7%). Medication name, description, and adverse reaction were mentioned in all PIs. Other items such as patient counseling information (98%), warnings (95.2%), precautions (95.2%), pregnancy/lactation (95%), and storage condition (90.5%) have been mentioned in a high percentage of PIs. CONCLUSION: PIs have improved in recent years in Iran, but there is an absolute need for more accurate and up-to-date information. The IFDA should supervise pharmaceutical companies more strictly in this regard and should revise its regulations requiring PIs to conform to the FDA regulations.

Management of Hypotension and Bradycardia Caused By Spinal Cord Injury. The Usefulness of Midodrine and Methylxanthines.

Spinal cord injury is a devastating chronic condition resulting in temporary or permanent motor, sensory or autonomic dysfunction of the cord. The manifestation of spinal cord injury based on the severity and involved areas could be different. Numerous studies have demonstrated that bradycardia, hypotension, and orthostatic hypotension are present insignificant number of patients after spinal cord injury which peaks at 4th day of injury. Although vasopressors are common drugs that have been used to restore blood pressure and heart rate in patients with neurogenic shock, there is limited data regarding pharmacologic management of bradycardia and hypotension after spinal cord injury. Midodrine is a potent vasopressor approved for the management of symptomatic orthostatic hypotension. Theophylline and aminophylline are methylxanthine derivatives. There are very few case reports concerning the use of midodrine and methylxanthines for treatment of hypotension in patients with spinal cord injury. In this case report and review of the articles we report a 45 year old woman with a diagnosis of spinal cord injury who was successfully managed with midodrine and aminophylline and then we review current case reports. Based on our case report and other available data, midodrine as well as methylxanthines can be suggested as therapeutic options for managing symptoms in spinal cord injury patients.

The Relationship between Fatigue and Cytokine Levels in Patients with Acute Myeloid Leukemia.

Background: Cancer-related fatigue (CRF) is a very prominent complaint and disabling symptom in cancer patients probably influenced by endogenous cytokines. But, the published data on this subject are limited. We explored the relationship of cytokines such as tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) with fatigue in patients with AML. Materials and Methods: This study was performed on 45 patients (25 men, 20 women) with newly diagnosed AML. We examined fatigue in these patients with validated questionnaire. Simultaneously, blood samples were obtained for quantitative measurement of IL-6 and TNF-α. Results: Our results showed a positive correlation between fatigue and circulating levels of IL-6 (P=0.004, R=0.416). Conclusion: Many patients with AML experienced severe fatigue before the onset of treatment, which is not related to their hemoglobin (Hb) levels. Cytokine levels may be beneficial markers in resistance to fatigue, but further studies are needed before considering targeted therapies as a treatment for CRF.