Acute exacerbations of chronic obstructive pulmonary disease (COPD) can be prevented by inhaled treatment. Errors in inhaler handling, not taken into account in clinical trials, could impact drug delivery and minimise treatment benefit. We aimed to assess real-life inhaler device handling in COPD patients and its association with COPD exacerbations.To this end, 212 general practitioners and 50 pulmonologists assessed the handling of 3393 devices used for continuous treatment of COPD in 2935 patients. Handling errors were observed in over 50% of handlings, regardless of the device used. Critical errors compromising drug delivery were respectively made in 15.4%, 21.2%, 29.3%, 43.8%, 46.9% and 32.1% of inhalation assessment tests with Breezhaler® (n=876), Diskus® (n=452), Handihaler® (n=598), pressurised metered-dose inhaler (pMDI) (n=422), Respimat® (n=625) and Turbuhaler® (n=420).The proportion of patients requiring hospitalisation or emergency room visits in the past 3 months for severe COPD exacerbation was 3.3% (95% CI 2.0-4.5) in the absence of error and 6.9% (95% CI 5.3-8.5) in the presence of critical error (OR 1.86, 95% CI 1.14-3.04, p<0.05).Handling errors of inhaler devices are underestimated in real life and are associated with an increased rate of severe COPD exacerbation. Training in inhaler use is an integral part of COPD management.

BackgroundMost NSAIDs are thought to be able to cause hepatic injury and acute liver failure (ALF), but the event rates of those leading to transplantation (ALFT) remain uncertain.ObjectivesThe aim of the study was to estimate population event rates for NSAID-associated ALFTMethodsThis was a case-population study of ALFT in 57 eligible liver transplant centres in seven countries (France, Greece, Ireland, Italy, The Netherlands, Portugal and the UK). Cases were all adults registered from 2005 to 2007 for a liver transplant following ALFT without identified clinical aetiology, exposed to an NSAID or paracetamol (acetaminophen) within 30 days before the onset of clinical symptoms. NSAID and paracetamol population exposures were assessed using national sales data from Intercontinental Marketing Services (IMS). Risk was estimated as the rate of ALFT per million treatment-years (MTY).ResultsIn the 52 participating centres, 9479 patients were registered for transplantation, with 600 for ALFT, 301 of whom, without clinical aetiology, had been exposed to a drug within 30 days. Of these 301 patients, 40 had been exposed to an NSAID and 192 to paracetamol (81 of whom were without overdose).Event rates per MTY were 1.59 (95 % CI 1.1–2.2) for all NSAIDs pooled, 2.3 (95 % CI 1.2–3.9) for ibuprofen, 1.9 (95 % CI 0.8–3.7) for nimesulide, 1.6 (95 % CI 0.6–3.4) for diclofenac and 1.6 (95 % CI 0.3–4.5) for ketoprofen. For paracetamol, the event rate was 3.3 per MTY (95 % CI 2.6–4.1) without overdoses and 7.8 (95 % CI 6.8–9.0) including overdoses.ConclusionsALF leading to registration for transplantation after exposure to an NSAID was rare, with no major difference between NSAID. Non-overdose paracetamol-exposed liver failure was twice more common than NSAID-exposed liver failure.Electronic supplementary materialThe online version of this article (doi:10.1007/s40264-012-0013-7) contains supplementary material, which is available to authorized users.

Background Nonsteroidal anti-inflammatory drugs (NSAIDs) have been discouraged for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, fearing that they could increase the risk of infection or the severity of SARS-CoV-2. Methods Original studies providing information on exposure to NSAIDs and coronavirus disease 2019 (COVID-19) outcomes were retrieved and were included in a descriptive analysis and a meta-analysis with Cochrane Revue Manager (REVMAN 5.4), using inverse variance odds ratio (OR) with random- or fixed-effects models. Results Of 92,853 papers mentioning COVID-19, 266 mentioned NSAIDs and 61 mentioned ibuprofen; 19 papers had analysable data. Three papers described NSAID exposure and the risk of SARS-CoV-2 positivity, five papers described the risk of hospital admission in positive patients, 10 papers described death, and six papers described severe composite outcomes. Five papers studied exposure to ibuprofen and death. Using random-effects models, there was no excess risk of SARS-CoV-2 positivity (OR 0.86, 95% confidence interval [CI] 0.71–1.05). In SARS-CoV-2-positive patients, exposure to NSAIDs was not associated with excess risk of hospital admission (OR 0.90, 95% CI 0.80–1.17), death (OR 0.88, 95% CI 0.80–0.98), or severe outcomes (OR 1.14, 95% CI 0.90–1.44). With ibuprofen, there was no increased risk of death (OR 0.94, 95% CI 0.78–1.13). Using a fixed-effect model did not modify the results, nor did the sensitivity analyses. Conclusion The theoretical risks of NSAIDs or ibuprofen in SARS-CoV-2 infection are not confirmed by observational data. Supplementary Information The online version contains supplementary material available at 10.1007/s40264-021-01089-5.