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Baseline Drug Treatments as Indicators of Increased Risk of COVID-19 Mortality in Spain and Italy

Bliek-Bueno et al., International Journal of Environmental Research and Public Health, doi:10.3390/ijerph182211786
Nov 2021  
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Mortality, combined -87% Improvement Relative Risk Mortality, Campania -170% Mortality, Aragon -59% Vitamin B9  Bliek-Bueno et al.  Prophylaxis Is prophylaxis with vitamin B9 + Vitamin B12 beneficial for COVID-19? Retrospective 8,570 patients in multiple countries (Mar - Apr 2020) Higher mortality with vitamin B9 + Vitamin B12 (p<0.000001) c19early.org Bliek-Bueno et al., Int. J. Environmen.., Nov 2021 Favorsvitamin B9 Favorscontrol 0 0.5 1 1.5 2+
Retrospective 8,570 individuals in Spain and Italy, showing higher mortality with combined vitamin B9 and B12 supplementation. Adjustments only considered age.
risk of death, 87.4% higher, OR 1.87, p < 0.001, combined, RR approximated with OR.
risk of death, 170.0% higher, OR 2.70, p < 0.001, Campania, RR approximated with OR.
risk of death, 59.0% higher, OR 1.59, p < 0.001, Aragon, RR approximated with OR.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Bliek-Bueno et al., 10 Nov 2021, retrospective, multiple countries, peer-reviewed, mean age 67.7, 15 authors, study period 4 March, 2020 - 17 April, 2020, this trial uses multiple treatments in the treatment arm (combined with Vitamin B12) - results of individual treatments may vary. Contact: sara.mucherino@unina.it (corresponding author), kbliek@salud.aragon.es, bpoblador.iacs@aragon.es, franciscagonzalezrubio@gmail.com, maza@salud.aragon.es, mclerencia@salud.aragon.es, ignatios.ioakeimskoufa@fhi.no, jcarmona@iisaragon.es, sprados.iacs@aragon.es, valentina.orlando@unina.it, enrica.menditto@unina.it, enrico.coscioni@regione.campania.it, alessandro.perrella@aocardarelli.it, ugo.trama@regione.campania.it, agimenomi.iacs@aragon.es.
This PaperVitamin B9All
Baseline Drug Treatments as Indicators of Increased Risk of COVID-19 Mortality in Spain and Italy
Kevin Bliek-Bueno, Sara Mucherino, Beatriz Poblador-Plou, Francisca González-Rubio, Mercedes Aza-Pascual-Salcedo, Valentina Orlando, Mercedes Clerencia-Sierra, Ignatios Ioakeim-Skoufa, Enrico Coscioni, Jonás Carmona-Pírez, Alessandro Perrella, Ugo Trama, Alexandra Prados-Torres, Enrica Menditto, Antonio Gimeno-Miguel
International Journal of Environmental Research and Public Health, doi:10.3390/ijerph182211786
This study aims to identify baseline medications that, as a proxy for the diseases they are dispensed for, are associated with increased risk of mortality in COVID-19 patients from two regions in Spain and Italy using real-world data. We conducted a cross-country, retrospective, observational study including 8570 individuals from both regions with confirmed SARS-CoV-2 infection between 4 March and 17 April 2020, and followed them for a minimum of 30 days to allow sufficient time for the studied event, in this case death, to occur. Baseline demographic variables and all drugs dispensed in community pharmacies three months prior to infection were extracted from the PRECOVID Study cohort (Aragon, Spain) and the Campania Region Database (Campania, Italy) and analyzed using logistic regression models. Results show that the presence at baseline of potassium-sparing agents, antipsychotics, vasodilators, high-ceiling diuretics, antithrombotic agents, vitamin B12, folic acid, and antiepileptics were systematically associated with mortality in COVID-19 patients from both countries. Treatments for chronic cardiovascular and metabolic diseases, systemic inflammation, and processes with increased risk of thrombosis as proxies for the conditions they are intended for can serve as timely indicators of an increased likelihood of mortality after the infection, and the assessment of pharmacological profiles can be an additional approach to the identification of at-risk individuals in clinical practice.
Supplementary Materials: The following are available online at https://www.mdpi.com/article/10 .3390/ijerph182211786/s1. Table S1 : Dispensation rates of the complete list of drugs studied and adjusted odds ratios of 30-day mortality in each region. Funding: This research was funded by the Government of Aragon through the Recognized Groups Grant reference B01_20R and Decree-Law 3/2020, published on 3 June. Author Contributions: Institutional Review Board Statement: The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Clinical Research Ethics Committee of Aragón (CEICA; Protocol number PI20/226). CEICA waived the requirement to obtain informed consent from Aragon participants due to the epidemiological nature of the project and the use of anonymized data that was presented at an aggregated level. The governance board of Unità del Farmaco della Regione Campania granted permission to the researchers of the CIRFF to use anonymized data for this study. Conflicts of Interest: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data, in the writing of the manuscript or in the decision to publish the results.
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