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0 0.5 1 1.5 2+ Death/hospitalization -15% Improvement Relative Risk Death/hospitalization (b) -29% Death/hospitalization (c) -75% late Acetaminophen  Lapi et al.  EARLY TREATMENT Is early treatment with acetaminophen beneficial for COVID-19? Retrospective study in Italy No significant difference in death/hosp. Lapi et al., Internal and Emergency Me.., Jul 2022 Favors acetaminophen Favors control

To clarify the safety profile of paracetamol for home-care patients with COVID-19: a real-world cohort study, with nested case–control analysis, in primary care

Lapi et al., Internal and Emergency Medicine, doi:10.1007/s11739-022-03054-1
Jul 2022  
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Retrospective paracetamol use with a primary care database in Italy, showing no significant difference in hospitalization/death for use 0-3 and 4-7 days from diagnosis, and significantly higher risk for use >7 days from diagnosis. Confounding by indication may have a greater effect on late usage. Paracetamol is also known as acetaminophen, Tylenol, Panadol, Calpol, Tempra, Calprofen, Doliprane, Efferalgan, Grippostad C, Dolo, Acamol, Fevadol, Crocin, and Perfalgan.
risk of death/hospitalization, 15.0% higher, OR 1.15, p = 0.22, adjusted per study, early use, RR approximated with OR.
risk of death/hospitalization, 29.0% higher, OR 1.29, p = 0.52, adjusted per study, mid-term use, RR approximated with OR.
risk of death/hospitalization, 75.0% higher, OR 1.75, p < 0.001, adjusted per study, late use, RR approximated with OR, late treatment result, excluded in exclusion analyses: substantial unadjusted confounding by indication likely.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Lapi et al., 30 Jul 2022, retrospective, Italy, peer-reviewed, 8 authors.
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To clarify the safety profile of paracetamol for home-care patients with COVID-19: a real-world cohort study, with nested case–control analysis, in primary care
Francesco Lapi, Ettore Marconi, Ignazio Grattagliano, Alessandro Rossi, Diego Fornasari, Alberto Magni, Pierangelo Lora Aprile, Claudio Cricelli
Internal and Emergency Medicine, doi:10.1007/s11739-022-03054-1
Background and objective This study aimed to compare the prescribing patterns of paracetamol in COVID-19 with those for similar respiratory conditions and investigated the association between paracetamol use and COVID-19-related hospitalization/death. Methods Using a primary care data source, we conducted a cohort study to calculate the incidence rate of paracetamol use in COVID-19 and for similar respiratory conditions in 2020 and 2019 (i.e. pre-pandemic phase), respectively. In the study cohort, we nested a case-control analyses to investigate the association between paracetamol use and COVID-19-related hospitalizations/deaths. Results Overall, 1554 (33.4 per 1000) and 2566 patients (78.3 per 1000) were newly prescribed with paracetamol to treat COVID-19 or other respiratory conditions, respectively. Those aged 35-44 showed the highest prevalence rate (44.7 or 99.0 per 1000), while the oldest category reported the lowest value (17.8 or 39.8 per 1000). There was no association for early (OR = 1.15; 95% CI: 0.92-1.43) or mid-term (OR = 1.29; 95% CI: 0.61-2.73) users of paracetamol vs. non-users. Instead, the late users of paracetamol showed a statistically significant increased risk of hospitalization/death (OR = 1.75; 95% CI: 1.4-2.2). Conclusions Our findings provide reassuring evidence on the use and safety profile of paracetamol to treat early symptoms of COVID-19 as in other respiratory infections.
Supplementary Information The online version contains supplementary material available at https:// doi. org/ 10. 1007/ s11739-022-03054-1. Authors contribution FL, IG, AR, DF, EM, AM, PLA and CC: have made substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data. FL, EM, IG, DF, PLR and CC: have been involved in drafting the manuscript or revising it critically for important intellectual content. CC: is responsible for the integrity of the work, and he given final approval of the version to be published. Each author should have participated sufficiently in the work to take public responsibility for appropriate portions of the content. FL: agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Conflict of interest FL and EM provided consultancies in protocol preparation for epidemiological studies and data analyses for Angelini, Pfizer, and GSK. AR, IG, AM, PLA, and CC provided clinical consultancies for Angelini, Pfizer, and GSK. DF has no conflict of interest to disclose. Ethical approval According to a by-law on the classification and implementation of observational drug-related research, as issued by the Italian National Drug Agency (an entity belonging to the Italian Ministry of Health), the present study does not require approval by an Ethics Committee in Italy (Italian Drug Agency..
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