Approaches to Assessing the Safety of Medicines during the COVID-19 Pandemic Using the Example of Azithromycin

Most of the medicines used to treat the novel coronavirus infection (COVID-19) are either approved under an accelerated procedure or not approved for the indication. Consequently, their safety requires special attention. The aim of the study was to review methodological approaches to collecting data on the safety of medicines, using COVID-19 treatment regimens involving azithromycin as a case study. Material(s) and Method(s): PubMed (MEDLINE), Scopus, eLIBRARY, and Cyberleninka databases were searched for publications on azithromycin as part of combination therapy for COVID-19 in 2020-2021. Search queries included names of the medicinal product or its pharmacotherapeutic group and words describing adverse drug reactions (ADRs) during treatment. Result(s): the analysis included 7 publications presenting the results of studies covering the use of azithromycin as part of COVID-19 combination therapy in more than 4000 patients. Most commonly, the patients receiving COVID-19 therapy including azithromycin developed cardiovascular ADRs (up to 30% of azithromycin prescription cases). In 3 of the analysed publications, safety information was collected through spontaneous reporting and active identification based on the findings of laboratory and instrumental investigations performed during the clinical studies;in other 3, only spontaneous reports were used;and in the last one, ADR database information was studied. Conclusion(s): currently, information on ADRs associated with the use of medicines is mainly gathered via spontaneous reporting. Direct sourcing of information on personal experiences with a certain product from patients, among other means through social media analysis, opens a promising direction towards the improvement of existing approaches to collecting safety data. Copyright © 2022 Obstetrics, Gynecology and Reproduction. All rights reserved.

A systematic review and meta-analysis of the safety of anti-interleukin therapy in COVID-19

Objective. To evaluate safety of anti-interleukin drugs used as a pathogenetic therapy of COVID-19 as assessed by risks of infectious complications. Materials and methods. A systematic review of publications related to safety assessment of anti-interleukin drugs recommended as pathogenetic therapy in COVID-19 patients in terms of incidence of serious adverse events and adverse events of “Infections and Invasions” class and a meta-analysis of the data were performed. Results. The meta-analysis included 16 randomized and 3 non-randomized studies. The hazard ratio of serious adverse events between the comparison groups was 0.93 [95% CI 0.85;1.01] (p = 0.1), the hazard ratio of adverse event of “Infections and Invasions” class was 0.9 [95% CI 0.8;1.02] (p = 0.09), showing no differences in the incidence of those events. Conclusions. This meta-analysis did not demonstrate statistically significant differences in the relative risks of serious adverse events and adverse events of “Infections and Invasions” class for the use of anti-interleukin drugs in COVID-19 patients. © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

[Experience of anticipatory therapy with IL-6 receptor inhibitors and perspectives for its use in the evolution of COVID-19].

The Advisory Board chaired by the chief specialist in infectious diseases of the Ministry of Health of Russian Federation, Professor V.P. Chulanov was held on June 18, 2022 in Saint Petersburg. Aim. The main purpose of the Board was following discussion: the analysis of the real-world data of levilimab as an anticipatory therapy for COVID-19 in hospitalized patients; the review of the experience and perspectives of levilimab as an anticipatory anti-inflammatory option for outpatient patients who meet defined clinical and laboratory criteria. Results. The analyzed data on clinical efficacy and safety formed the basis of recommendations proposed by experts for the use of levilimab in the inpatient and outpatient medical care for COVID-19.

A systematic review of real-world clinical practice data in COVID-19: non-interventional studies

Introduction. As defined by the Food and Drug Administration, real-world data (RWD) is data related to a patient's health and/or health care delivery, usually collected from various sources as part of real-world clinical practice research. Objective: to describe the feasible and the most sought-after designs of non-interventional real-world clinical practice trials that provide evidence for the efficacy and safety of drug administration in the therapy of novel coronavirus infection. Material and methods. A search strategy for the terms “COVID-19 AND real-life”, “COVID-19 AND real-data”, “COVID-19 AND real-world” was developed to extract articles published between December 1, 2020 and March 12, 2021 from the databases: PubMed/MEDLINE, the Cochrane Database of Systematic Reviews, and the ClinicalTrials.gov database. Results. The search yielded 137 non-repetitive articles, 32 of them were included in the review. All randomized clinical trials (pragmatic and simplified large ones), studies of the effectiveness of laboratory diagnostic methods, medical triage, social distancing and other sanitary and epidemiological measures to cope with the epidemic were excluded. Conclusion. High-quality, non-randomized RWD studies can enhance the external validity of registration randomized clinical trials by complementing them with a broader range of indicators, which is essential in supporting medical and public health decision-making in the COVID-19 pandemic.

Treatment of Proximal Femoral Fractures in Patients with COVID-19

Background. In relation with the COVID-19 new coronavirus infection epidemic that began in Russia in the spring of 2020, a completely new group of patients appeared: patients whose coronavirus infection was combined with the proximal femur fractures. In the course of practical work, hospital doctors had to gain experience in treating these complex patients, solve new organizational and medical tasks. The aim of the study was to evaluate the results of treatment of patients with the proximal femur fractures in combination with coronavirus infection in a "covid" hospital at the hospital stage, 30-day and 6-month terms. Materials and Methods. The retrospective study is based on the collection and generalization of data from 64 patients with the proximal femur fractures in combination with confirmed coronavirus infection who underwent inpatient treatment from 16.03.2020 to 31.05.2021. 38 (59.4%) patients had a femoral neck fracture, 26 (40.6%) had a fracture of the trochanter region. Forty (62.5%) patients underwent surgical treatment (hip replacement was performed in 23 cases, osteosynthesis was performed in 17 cases), 24 (37.5%) patients did not undergo surgery. Results. With conservative treatment, the hospital mortality rate was 41.6%, the 30-day mortality rate was 72.7%, and the 6 - month mortality rate was 95.5%. During surgical treatment, the hospital mortality rate was 5.0% (2 patients died). Early postoperative complications were detected in 5 (12.5%) patients. Thirty-one (77.5%) patients walked or stood with a walker on their own at the time of discharge;7 (17.5%) patients could not be activated. The thirty-day mortality rate in the group of patients who underwent surgical treatment was 8.6%, and the 6-month mortality rate was 32.1%. Conclusion. Surgical treatment of patients with the proximal femur fractures in combination with coronavirus infection is much more difficult than the treatment of patients without infectious pathology. However, despite number of unresolved problems, surgical treatment of such patients is possible with good results and should be actively applied.

Spontaneous retroperitoneal hematoma in a COVID-19: The first clinical practice

Justification. Diagnostics, surgical tactics, postoperative treatment of spontaneous retroperitoneal hematoma (SRH) are still a complex section in medicine. The mortality rate of SRH is high and amounts to about 20%. Scientific interest to the problem of SRH has arisen with the rapid worldwide spread of COVID-19 since the end of 2019. Due to the widespread use of anticoag-ulants and the development of COVID-19-associated coagulopathy, the incidence of retroperitoneal hematomas in patients with COVID-19 is higher than in the general population. Materials and methods. Throughout the year more than 16806 COVID-19patients were assisted. Of these, SRH developed in 5 patients. Results. SRH was found posthumously in 2 patients. Emergency surgery — lumbotomy with revision of the retroperitoneum — was performed in three patients. Conclusions. Low molecular weight heparin and other members of the anticoagulant group can cause severe hemorrhagic com-plications in COVID-19 patients. © 2021, Media Sphera Publishing Group. All rights reserved.