Tehran University Medical Journal

Background: Amphotericin B is one of the most useful therapeutic modalities for the treatment of patients with invasive fungal infections, in spite of serious side effects, namely kidney injury, electrolyte imbalances, and infusion-related reactions. The goal of this study was to assess the different aspects of premedication practice and the incidence and types of infusion-related reactions in patients receiving amphotericin B.
Methods: This observational study was performed on 70 hospitalized patients who received amphotericin B in different departments of two university hospitals, affiliated to Isfahan University of Medical Sciences, Isfahan, Iran, from January 2017 to February 2018. Information on physicians’ performance regarding premedication administration for amphotericin B, including the types and doses of medications administered prior to amphotericin B infusion, as well as patients’ clinical data including infusion-related side effects were collected and then analyzed in comparison with the standard practice guidelines.
Results: The study population consisted of 70 patients with the mean age of 51.6±18.3 years, who received amphotericin B for 8.2±3.5 days. From 70 evaluated patients, 21 patients (30%) had encountered the infusion-related reactions, including chills, fever, urticaria, headache, and hypotension. These side effects were evident in 19 patients (27%) who received no premedication and 2 patients (3%) who received only one drug as premedication, before amphotericin B administration. Twenty patients (28%) experienced chills, fever and headache, while 7 patients (10%) had nausea and vomiting during amphotericin B infusion. Hydrocortisone 50-200 mg, was the most prescribed agent for premedication (in 67% of patients), while chlorpheniramine 10 mg (in 50% of patients) and promethazine 10 mg (in 35% of patients) were the second and third prescribed ones, respectively.
Conclusion: In this study, the patients who received no or only one drug as premedication experienced infusion-related side effects. This emphasizes the necessity for standard premedication practices to prevent this type of adverse reactions. Considering the higher price of liposomal form of Amphotericin-B, if prescribed correctly, even the conventional form would be an effective and tolerable treatment for invasive fungal infections.

Background: Mendelian randomization (MR) is a new generation in the statistical method that uses genetic variants as instrumental variables in data from non-experimental studies to evaluate and estimate the causal effects of risk factors.
Methods: The weakness of observational studies to detect causality, the difficulties of conducting clinical trials, the dramatic advancement of Genome-Wide Association Studies (GWAS) have led to the emergence of a new type of study called MR. It is increasingly being used to determine causality MR is an approach based on meta-analysis methods. The main idea of the MR is based on using the instrument variable (IV) to find the causality between exposure and outcome. This variable does not need to adjust the confounding effects found in observational studies.

Results: Data for this study were collected from the beginning of January 2003 to October 2020 in PubMed. Our results showed that MR has an increasing trend. The data used in MR includes summarized statistical data, individual-level data, and meta-analysis. Choosing the suitable IV is essential to successfully conduct an MR. For an unbiased estimate, three main hypotheses should be considered: 1) The IV has a strong relationship with the desired exposure (i.e., potential risk factor), 2) The IV is not related to the confounding variable, and 3) The IV is not directly related to the outcome and should only relate to the outcome through exposure. If these conditions are not met, one solution is to use robust methods. Besides, this research introduced the study designs, estimation methods, limitations, software packages, and some applications of MR in medical research. Conclusion: When we seek to find a causal relationship, but it is not possible to use a clinical trial as a standard method, the MR design can be used in observational studies. Therefore, it is possible to obtain causal relationships between exposure and outcome using the MR.