Detection of potential safety signals related to the use of remdesivir and tocilizumab in the COVID era during pregnancy, resorting to open data from the FDA adverse event reporting system (FAERS)

Background: The in-hospital treatment for COVID-19 may include medicines from various therapeutic classes, such as antiviral remdesivir and immunosuppressant tocilizumab. Safety data for these medicines are based on controlled clinical trials and case reports, limiting the knowledge about less frequent, rare or unique population adverse events excluded from clinical trials.Objective: This study aims at analyzing the reports of Adverse Drug Events (ADEs) related to these two medicines, focusing on events in pregnant women and foetuses.Methods: Data from the open-access FDA Adverse Event Reporting System (FAERS) from 2020 to 2022 were used to create a dashboard on the Grafana platform to ease querying and analyzing report events. Potential safety signals were generated using the ROR disproportionality measure.Results: Remdesivir was notified as the primary suspect in 7,147 reports and tocilizumab in 19,602. Three hundred and three potential safety signals were identified for remdesivir, of which six were related to pregnant women and foetuses (including abortion and foetal deaths). Tocilizumab accumulated 578 potential safety signals, and three of them were associated with this population (including neonatal death).Discussion: None of the possible signals generated for this population were found in the product labels. According to the NIH and the WHO protocols, both medicines are recommended for pregnant women hospitalized with COVID-19.Conclusion: Despite the known limitations of working with open data from spontaneous reporting systems (e.g., absence of certain clinical data, underreporting, a tendency to report severe events and recent medicines) and disproportionality analysis, the findings suggest concerning associations that need to be confirmed or rejected in subsequent clinical studies

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Minerador de eventos adversos maláricos no Twitter O caso da Doxiciclina

Submitted by Gilvan Almeida ([email protected]) on 2017-01-02T12:16:30Z No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) 72247.pdf: 1988266 bytes, checksum: 8ab1fe996a4717d04c549f0f9b3bc26c (MD5)Approved for entry into archive by Anderson Silva ([email protected]) on 2017-04-07T13:41:54Z (GMT) No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) 72247.pdf: 1988266 bytes, checksum: 8ab1fe996a4717d04c549f0f9b3bc26c (MD5)Made available in DSpace on 2017-04-07T13:41:54Z (GMT). No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) 72247.pdf: 1988266 bytes, checksum: 8ab1fe996a4717d04c549f0f9b3bc26c (MD5) Previous issue date: 2016Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, BrasilDurante o período de pós-comercialização, quando medicamentos são usados por grandes populações e por períodos de tempo maiores, eventos adversos inesperados podem ocorrer, o que altera a relação risco-benefício dos medicamentos o suficiente para exigir uma ação regulatória. Eventos adversos no período de pós-comercialização podem requerer um aumento significativo de cuidados de saúde e resultar em danos desnecessários, muitas vezes fatais, aos pacientes. Portanto, a descoberta o quanto antes de eventos adversos no período de pós-comercialização é um objetivo principal do sistema de saúde. Alguns países possuem sistemas de vigilância farmacológica responsáveis pela coleta de relatórios voluntários de eventos adversos na pós-comercialização, mas estudos já demonstraram que com a utilização de redes sociais como o Twitter, pode-se conseguir um número maior de relatórios. O objetivo principal desse projeto é construir um sistema totalmente automatizado que utilize o Twitter como fonte para encontrar eventos adversos novos e já conhecidos e fazer a análise estatística dos dados obtidos. Para tal, foi construído um sistema que coleta, processa, analisa e avalia tweets em busca de eventos adversos, comparando-os com dados da FDA e do padrão de referência construído. Nos resultados obtidos conseguimos encontrar eventos adversos novos e já existentes relacionados ao medicamento doxiciclina o que demonstra que o Twitter pode sim, ser útil para a Farmacovigilância quando utilizado em conjunto com outras fontes de dadosAt the post-marketing phase when drugs are used by large populations and for long periods, unexpected adverse events may occur altering the risk-benefit trade off of drugs, sometimes requiring a regulatory action. These events at the post-marketing phase require a significant increase in health care since they result in unnecessary damage, often fatal, to patients. Therefore, the early discovery of adverse events in the post-marketing phase is a primary goal of the health system. Some countries have pharmacovigilance systems used to collect voluntary reports of adverse events from post-marketing, but studies have shown that with the use of social networks like Twitter, you can get a greater number of reports. The main objective of this project is to build a fully automated system that uses Twitter as a source to find new and already known adverse events and do statistical analysis of the data. To achieve this, we build a system that collects, processes, analyzes and evaluates tweets in searching for adverse events and comparing them with the FDA data and gold standard built. New and already known adverse events related to the doxycycline drug were found in the result, which shows that Twitter can indeed be useful for pharmacovigilance when used with other data source

O uso do Twitter como minerador de eventos adversos de medicamentos de combate à malária: o caso da doxiciclina

Durante o período de pós-comercialização, quando medicamentos são usados por grandes populações e por períodos de tempo maiores, eventos adversos (EA) inesperados podem ocorrer, o que pode alterar a relação risco-benefício dos medicamentos o suficiente para exigir uma ação regulatória. Eventos adversos são agravos à saúde que podem surgir durante o tratamento com um produto farmacêutico, os quais, no período de pós-comercialização do medicamento, podem requerer um aumento significativo de cuidados de saúde e resultar em danos desnecessários aos pacientes, muitas vezes fatais. Portanto, o quanto antes, a descoberta de EA no período de pós-comercialização é um objetivo principal do sistema de saúde. Alguns países possuem sistemas de vigilância farmacológica responsáveis pela coleta de relatórios voluntários de EA na pós-comercialização, mas estudos já demonstraram que, com a utilização de redes sociais, pode-se conseguir um número maior e mais rápido de relatórios. O objetivo principal deste projeto é construir um sistema totalmente automatizado que utilize o Twitter como fonte para encontrar EA novos e já conhecidos e fazer a análise estatística dos dados obtidos. Para isso, foi construído um sistema que coleta, processa, analisa e avalia tweets em busca de EA, comparando-os com dados da Agência Americana de Controle de Alimentos e Medicamentos (FDA) e do padrão de referência construído. Nos resultados obtidos, conseguimos encontrar EA novos e já existentes relacionados ao medicamento doxiciclina, o que demonstra que o Twitter, quando utilizado em conjunto com outras fontes de dados, pode ser útil para a farmacovigilância

DataSheet1_Detection of potential safety signals related to the use of remdesivir and tocilizumab in the COVID era during pregnancy, resorting to open data from the FDA adverse event reporting system (FAERS).docx

Background: The in-hospital treatment for COVID-19 may include medicines from various therapeutic classes, such as antiviral remdesivir and immunosuppressant tocilizumab. Safety data for these medicines are based on controlled clinical trials and case reports, limiting the knowledge about less frequent, rare or unique population adverse events excluded from clinical trials.Objective: This study aims at analyzing the reports of Adverse Drug Events (ADEs) related to these two medicines, focusing on events in pregnant women and foetuses.Methods: Data from the open-access FDA Adverse Event Reporting System (FAERS) from 2020 to 2022 were used to create a dashboard on the Grafana platform to ease querying and analyzing report events. Potential safety signals were generated using the ROR disproportionality measure.Results: Remdesivir was notified as the primary suspect in 7,147 reports and tocilizumab in 19,602. Three hundred and three potential safety signals were identified for remdesivir, of which six were related to pregnant women and foetuses (including abortion and foetal deaths). Tocilizumab accumulated 578 potential safety signals, and three of them were associated with this population (including neonatal death).Discussion: None of the possible signals generated for this population were found in the product labels. According to the NIH and the WHO protocols, both medicines are recommended for pregnant women hospitalized with COVID-19.Conclusion: Despite the known limitations of working with open data from spontaneous reporting systems (e.g., absence of certain clinical data, underreporting, a tendency to report severe events and recent medicines) and disproportionality analysis, the findings suggest concerning associations that need to be confirmed or rejected in subsequent clinical studies.</p

Paediatric COVID-19 mortality: a database analysis of the impact of health resource disparity

Background The impact of the COVID-19 pandemic on paediatric populations varied between high-income countries (HICs) versus low-income to middle-income countries (LMICs). We sought to investigate differences in paediatric clinical outcomes and identify factors contributing to disparity between countries.Methods The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) COVID-19 database was queried to include children under 19 years of age admitted to hospital from January 2020 to April 2021 with suspected or confirmed COVID-19 diagnosis. Univariate and multivariable analysis of contributing factors for mortality were assessed by country group (HICs vs LMICs) as defined by the World Bank criteria.Results A total of 12 860 children (3819 from 21 HICs and 9041 from 15 LMICs) participated in this study. Of these, 8961 were laboratory-confirmed and 3899 suspected COVID-19 cases. About 52% of LMICs children were black, and more than 40% were infants and adolescent. Overall in-hospital mortality rate (95% CI) was 3.3% [=(3.0% to 3.6%), higher in LMICs than HICs (4.0% (3.6% to 4.4%) and 1.7% (1.3% to 2.1%), respectively). There were significant differences between country income groups in intervention profile, with higher use of antibiotics, antivirals, corticosteroids, prone positioning, high flow nasal cannula, non-invasive and invasive mechanical ventilation in HICs. Out of the 439 mechanically ventilated children, mortality occurred in 106 (24.1%) subjects, which was higher in LMICs than HICs (89 (43.6%) vs 17 (7.2%) respectively). Pre-existing infectious comorbidities (tuberculosis and HIV) and some complications (bacterial pneumonia, acute respiratory distress syndrome and myocarditis) were significantly higher in LMICs compared with HICs. On multivariable analysis, LMIC as country income group was associated with increased risk of mortality (adjusted HR 4.73 (3.16 to 7.10)).Conclusion Mortality and morbidities were higher in LMICs than HICs, and it may be attributable to differences in patient demographics, complications and access to supportive and treatment modalities

Thrombotic and hemorrhagic complications of COVID-19 in adults hospitalized in high-income countries compared with those in adults hospitalized in low- and middle-income countries in an international registry

Background: COVID-19 has been associated with a broad range of thromboembolic, ischemic, and hemorrhagic complications (coagulopathy complications). Most studies have focused on patients with severe disease from high-income countries (HICs). Objectives: The main aims were to compare the frequency of coagulopathy complications in developing countries (low- and middle-income countries [LMICs]) with those in HICs, delineate the frequency across a range of treatment levels, and determine associations with in-hospital mortality. Methods: Adult patients enrolled in an observational, multinational registry, the International Severe Acute Respiratory and Emerging Infections COVID-19 study, between January 1, 2020, and September 15, 2021, met inclusion criteria, including admission to a hospital for laboratory-confirmed, acute COVID-19 and data on complications and survival. The advanced-treatment cohort received care, such as admission to the intensive care unit, mechanical ventilation, or inotropes or vasopressors; the basic-treatment cohort did not receive any of these interventions. Results: The study population included 495,682 patients from 52 countries, with 63% from LMICs and 85% in the basic treatment cohort. The frequency of coagulopathy complications was higher in HICs (0.76%-3.4%) than in LMICs (0.09%-1.22%). Complications were more frequent in the advanced-treatment cohort than in the basic-treatment cohort. Coagulopathy complications were associated with increased in-hospital mortality (odds ratio, 1.58; 95% CI, 1.52-1.64). The increased mortality associated with these complications was higher in LMICs (58.5%) than in HICs (35.4%). After controlling for coagulopathy complications, treatment intensity, and multiple other factors, the mortality was higher among patients in LMICs than among patients in HICs (odds ratio, 1.45; 95% CI, 1.39-1.51). Conclusion: In a large, international registry of patients hospitalized for COVID-19, coagulopathy complications were more frequent in HICs than in LMICs (developing countries). Increased mortality associated with coagulopathy complications was of a greater magnitude among patients in LMICs. Additional research is needed regarding timely diagnosis of and intervention for coagulation derangements associated with COVID-19, particularly for limited-resource settings

The LHCb upgrade I

International audienceThe LHCb upgrade represents a major change of the experiment. The detectors have been almost completely renewed to allow running at an instantaneous luminosity five times larger than that of the previous running periods. Readout of all detectors into an all-software trigger is central to the new design, facilitating the reconstruction of events at the maximum LHC interaction rate, and their selection in real time. The experiment's tracking system has been completely upgraded with a new pixel vertex detector, a silicon tracker upstream of the dipole magnet and three scintillating fibre tracking stations downstream of the magnet. The whole photon detection system of the RICH detectors has been renewed and the readout electronics of the calorimeter and muon systems have been fully overhauled. The first stage of the all-software trigger is implemented on a GPU farm. The output of the trigger provides a combination of totally reconstructed physics objects, such as tracks and vertices, ready for final analysis, and of entire events which need further offline reprocessing. This scheme required a complete revision of the computing model and rewriting of the experiment's software

The LHCb upgrade I

International audienceThe LHCb upgrade represents a major change of the experiment. The detectors have been almost completely renewed to allow running at an instantaneous luminosity five times larger than that of the previous running periods. Readout of all detectors into an all-software trigger is central to the new design, facilitating the reconstruction of events at the maximum LHC interaction rate, and their selection in real time. The experiment's tracking system has been completely upgraded with a new pixel vertex detector, a silicon tracker upstream of the dipole magnet and three scintillating fibre tracking stations downstream of the magnet. The whole photon detection system of the RICH detectors has been renewed and the readout electronics of the calorimeter and muon systems have been fully overhauled. The first stage of the all-software trigger is implemented on a GPU farm. The output of the trigger provides a combination of totally reconstructed physics objects, such as tracks and vertices, ready for final analysis, and of entire events which need further offline reprocessing. This scheme required a complete revision of the computing model and rewriting of the experiment's software

The LHCb upgrade I

International audienceThe LHCb upgrade represents a major change of the experiment. The detectors have been almost completely renewed to allow running at an instantaneous luminosity five times larger than that of the previous running periods. Readout of all detectors into an all-software trigger is central to the new design, facilitating the reconstruction of events at the maximum LHC interaction rate, and their selection in real time. The experiment's tracking system has been completely upgraded with a new pixel vertex detector, a silicon tracker upstream of the dipole magnet and three scintillating fibre tracking stations downstream of the magnet. The whole photon detection system of the RICH detectors has been renewed and the readout electronics of the calorimeter and muon systems have been fully overhauled. The first stage of the all-software trigger is implemented on a GPU farm. The output of the trigger provides a combination of totally reconstructed physics objects, such as tracks and vertices, ready for final analysis, and of entire events which need further offline reprocessing. This scheme required a complete revision of the computing model and rewriting of the experiment's software