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Objective: Data about the contribution of drugs to the development of acute kidney injury are scarce in hematological cancer patients. The current study evaluated the relationship between the use of different medications and acute kidney injury development in hematological cancer patients. Methods: This study was designed as a prospective observational cross-sectional study. All patients admitted to hematology wards of Shariati Hospital of Tehran University of Medical Sciences were evaluated, and patients younger than 18 years of age, those who were not able to consent to participate and those who presented with acute kidney injury were excluded. Acute kidney injury was diagnosed per KDIGO criteria. Results: Overall, 450 patients were evaluated in this study and 138 cases of acute kidney injury were detected; this translates into 30.6% incidence rate in hematology wards of the study center. The median age of the patients with acute kidney injury was 49 years and 84 (60.9%) of them were men. Length of hospital stay and mortality rate was significantly higher in patients with acute kidney injury than those without (P < .001 and < .001, respectively). Results of the multivariate analysis showed that treatment with vancomycin (odds ratio 1.77), the combination of vancomycin and amphotericin B deoxycholate (odds ratio 3.10), and idarubicin (odds ratio 2.10) could significantly increase the odds of acute kidney injury development in patients with hematological malignancy, but treatment with hydrocortisone (odds ratio 0.26) could have significant nephroprotective effects. Conclusion: This study showed that treatment with vancomycin, the combination of vancomycin and amphotericin B deoxycholate, and idarubicin could significantly increase the odds of acute kidney injury development. Hydrocortisone treatment showed significant nephroprotective effects. Mortality and duration of hospital stay were significantly higher in patients with acute kidney injury. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The genus Leptus (larvae) is revised based on type specimens and other specimens from species and locations worldwide. A total of 220 species were identified and divided into 8 morpho-groups, and 40 subgroups of species; the following synonymies were also made: Leptus (Leptus) eslamizadehi as a junior synonym of L. (L.) trimaculatus, L. (L.) ilzae as a junior synonym of L. (L.) kyushuensis, L. (L.) laplandicus as a junior synonym of L. (L.) clethrionomydis, L. (L.) alopecurus as a junior synonym of L. (L.) alvimordax, L. (L.) annikae as a junior synonym of L. (L.) cercopius, L. (L.) welbourni as a junior synonym of L. (L.) ghiradellae, L. (L.) laviniacus as a junior synonym of L. (L.) agenori, L. (L.) machilidis as a junior synonym of L. (L.) albertensis, L. (L.) gyas as a junior synonym of L. (L.) meloidarum, L. (L.) coloanensis as a junior synonym of L. (L.) astrubali, and L. (L.) sidorchukae as a junior synonym of L. (L.) maldonadoicus. In addition, tibial and tarsal chaetotactic maps are shown, leg chaetotaxy is discussed, and keys to species groups, subgroups, and species are included. We amended and provided new morphological data for 109 species. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction Acute lymphoblastic leukemia is an invasive malignancy which ought to be treated with several cytotoxic medications. Vincristine-based regimen is among the most commonly used regimens for the treatment of adult acute lymphoblastic leukemia. Peripheral neuropathy caused by vincristine provides a limitation in dose administration and can influence the treatment outcome and patient's quality of life. Case presentation Ileus and constipation occurred as a result of autonomic neuropathy in a 58-year-old man who underwent vincristine-based regimen for acute lymphoblastic leukemia treatment. Despite the administration of several laxative agents for constipation, the complication did not improve. So metoclopramide as a prokinetic agent was administered intravenously, and patient bowel movement and defecation started after 24 h. Conclusions There is no approved protocol for vincristine-induced autonomic neuropathy treatment; thus, prokinetic agents such as metoclopramide can be considered as an option for ileus treatment after ruling out the possibility of bowel obstruction. Prophylactic stool softeners should be administrated in all patients undergoing chemotherapy with vincristine to prevent gastrointestinal motility disorders. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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., Competing Interests: There are no conflicts of interest.

Objective: Acute brain injury is one of the leading causes of morbidity and mortality worldwide. Phenytoin has been commonly used as an anticonvulsant agent for the treatment or prophylaxis of seizures following acute brain injury. After a severe head injury, several pharmacokinetic changes occur. The aim of this study is the comparative evaluation of phenytoin serum concentration in patients with traumatic and nontraumatic brain injury (TBI)., Methods: This prospective observational study was performed on twenty adult brain injury patients who were admitted to an Intensive Care Unit and required phenytoin for the treatment or prophylaxis of postinjury seizures. For all the patients, phenytoin serum concentration was determined in three scheduled time points. Phenytoin serum concentration and pharmacokinetic parameters were compared between patients with TBI and cerebrovascular accident (CVA)., Findings: The V max and K m were significantly higher in head trauma (HT) patients than the CVA group. The phenytoin concentration (C p ) and the C p /dose ratio were significantly higher in the CVA group patients during the first sampling ( P < 0.05). The Acute Physiology and Chronic Health Evaluation П (APACHE П) score was significantly lower than the baseline at the end of the study in each group of patients ( P < 0.05). In addition, no significant correlation was observed between V max , K m , C p , C p /dose ratio, and APACHE II scores at the time of sampling., Conclusion: Due to significant differences in phenytoin plasma concentration and pharmacokinetic parameters between HT and CVA patients, close attention must be paid to the pharmacokinetic behavior of phenytoin in the efforts to improve the patient's outcome after a severe HT., Competing Interests: There are no conflicts of interest.

Objective: This study aimed to determine the portion of Iranian patients who attain therapeutic serum concentrations of voriconazole (VRCZ) following administration of fixed doses. In addition, the effect of CYP2C19 polymorphism on serum levels of VRCZ was also investigated., Methods: Forty-eight adult patients of Iranian origin with hematologic malignancies, who received VRCZ for treatment of invasive aspergillosis, were recruited into the study. Blood samples were drawn at day 4 of treatment to measure trough drug concentrations and determine genotyping of CYP2C19 polymorphisms of each patient. High-performance liquid chromatography method was used for measuring VRCZ serum level and CYP2C19 polymorphisms were conducted by Sanger sequencing. Demographic and clinical characteristics of patients alongside with CYP2C19 polymorphisms were assessed to determine the effective factor/s on VRCZ serum concentration., Findings: Seventy-three percent of patients achieved therapeutic serum concentrations of VRCZ with administration of usual fixed doses in clinical practice. There was no correlation between weight-adjusted dose and serum concentrations of VRCZ. Mean serum levels were significantly different neither in genders nor in routes of administrations. Extensive and ultrarapid metabolizers (URMs) comprised 48.7% and 21.6% study population, respectively. CYP2C19 polymorphism dramatically influenced the trough levels of VRCZ, so that all patients with subtherapeutic levels expressed URM phenotype., Conclusion: With respect to high incidence of URM phenotype in Iranian population, and observed association of this phenotype with sub-therapeutic levels in our study, performing therapeutic drug monitoring is strongly recommended for all patients., Competing Interests: There are no conflicts of interest.

Objective: Voriconazole as a triazole antifungal agent is widely used for prophylaxis or treatment of fungal infections in allogeneic hematopoietic stem cell transplantation (HSCT). It can increase blood concentrations of other medications including cyclosporine A (CsA) which are substrates for cytochrome P450 3A4. The aim of this study was to evaluate comparatively the interaction between oral/intravenous (IV) voriconazole and oral CsA., Methods: Twenty-nine recipients of allogeneic HSCT who had been already on a steady dose of CsA and were started on oral or IV voriconazole were evaluated in a prospective cohort study. Blood concentration of CsA was determined before and 5-8 days after voriconazole initiation. Plasma concentration of voriconazole was measured in steady state. The changes in blood concentration of CsA after administration of voriconazole were evaluated., Findings: The concentration/dose (C/D) ratio of CsA increased significantly ( P < 0.001) after voriconazole initiation in both routes of administration (8.40%-174.10% increase in C/D ratio). The C/D ratio alteration of CsA did not differ significantly between oral and IV voriconazole group ( P = 0.405). There was a significant correlation in all patients between plasma concentration of voriconazole and percentage of CsA C/D ratio increment ( P = 0.046)., Conclusion: There was a significant intrapatient variability in the magnitude of CsA blood concentration increment after voriconazole initiation. We also demonstrated that magnitude of drug interaction did not differ in IV and oral voriconazole administration. Furthermore, we found that the magnitude of drug interaction was correlated with plasma concentration of voriconazole., Competing Interests: There are no conflicts of interest.