Factors associated with serum creatinine and potassium after start of NSAID.

*<p>Adjusted for age, gender, exposure to potassium supplements, glucose lowering drugs and NSAIDs prescriber.</p>†<p>according to ATC classification.</p>‡<p>Risk level of renal failure/hyperkalemia caused by Drug-Drug Interactions (DDIs) between NSAIDs and antihypertensives (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0034187#pone-0034187-t001" target="_blank">table 1</a>).</p>§<p>in the 6 months before inclusion.</p>¶<p>Compared to other prescribers.</p

Characteristics of the first dispensing of NSAID.

<p>n, number; m, mean; sd, standard deviation; d, days; med, median; IQR, interquartile range; DDI Drug-Drug interaction.</p><p>NSAIDs, non steroidal anti-inflammatory drugs; DDD, defined Daily Dose;</p><p>Acetylsalicylic Acid: excluding anti-platelet dose.</p>‡<p>At risk of renal failure/hyperkalemia caused by Drug-Drug Interactions (DDIs) between NSAIDs and antihypertensives (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0034187#pone-0034187-t001" target="_blank">table 1</a>).</p

Selection of the 3,500 antihypertensive-treated patients with a first dispensing of NSAIDS.

<p>Selection of the 3,500 antihypertensive-treated patients with a first dispensing of NSAIDS.</p

Serum creatinine and potassium monitoring before^* and after start of NSAID.^†

<p>NSAIDs, non steroidal anti-inflammatory drugs.</p>*<p>in the year previous first NSAID dispensing.</p>†<p>in the 3 weeks after start of NSAID.</p>‡<p>At risk of renal failure/hyperkalemia caused by Drug-Drug Interactions (DDIs) between NSAIDs and antihypertensives (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0034187#pone-0034187-t001" target="_blank">table 1</a>).</p

Risk of renal failure/hyperkalemia caused by DDIs with NSAIDs according to classes of antihypertensive drugs.

<p>DDI, Drug-Drug Interaction; ACEIs, angiotensin converting enzyme inhibitors; ARBs, angiotensin receptor blockers.</p>‡<p>At risk of renal failure/hyperkalemia caused by Drug-Drug Interactions (DDIs) between NSAIDs and antihypertensives.</p

Overall cancer risk at doses in line with NDA, restricting the analysis to trials during at least 52 weeks (n = 13, continuity correction used: 0.01, I² = 0).

*<p>Restricted to trials with at least one event, n = 10.</p

Cancer Risk of Anti-TNF-α at Recommended Doses in Adult Rheumatoid Arthritis: A Meta-Analysis with Intention to Treat and per Protocol Analyses

<div><h3>Background</h3><p>The risk of malignancies on TNF-α antagonists is controversial. The aim of this survey was to assess cancer risk on TNF-α antagonists in adult rheumatoid arthritis patients, including the five marketed drugs (infliximab, etanercept, adalimumab, golimumab and certolizumab) used in line with the New Drug Application. Furthermore, the relative interest of modified intention to treat or per protocol analyses to assess such sparse events remains unknown.</p> <h3>Methodology/Principal Findings</h3><p>Data sources were MEDLINE, CENTRAL, ISI Web of Science, ACR and EULAR meeting abstracts, scientific evaluation of the drugs leading to their marketing approval, and clinicaltrials.gov, until 31 December 2012.We selected double-blind randomized controlled trials in adult rheumatoid arthritis patients, including at least one treatment arm in line with New Drug Application. We performed random effect meta-analysis, with modified intention to treat and per protocol analyses. Thirty-three trials were included. There was no excess risk of malignancies on anti-TNF-α administered in line with New Drug Application in the per protocol model (OR, 0.93 95%CI[0.59–1.44]), as well as in the modified intention to treat model (OR, 1.27 95%CI[0.82–1.98]). There was a non-significant tendency for an excess non-melanoma skin cancer risk in both models (respectively, 1.37 [0.71–2.66] and 1.90 [0.98–3.67]). With fixed effect Peto model restricting to trials during at least 52 weeks, the overall cancer risk was respectively 1.60 [0.97–2.64] and 1.22 [0.72–2.08]. Whatever the model, modified intention to treat analysis led to higher estimations than per protocol analysis. The later may underestimate the treatment effect when assessing very sparse events and when many patients dropped out in placebo arms. In metaregression, there was no differential risk among the five drugs.</p> <h3>Conclusions/Significance</h3><p>This study did not find any evidence for an excess cancer risk on TNF-α antagonists in adult rheumatoid arthritis patients, but an excess cancer risk after several years of exposure cannot be ruled out. Both modified intention to treat and per protocol analyses should be presented in such safety analyses.</p> </div

Table_1_The economic burden of asthma prior to death: a nationwide descriptive study.docx

BackgroundIn addition to the clinical burden, asthma is responsible for a high economic burden. However, little is known about the economic burden of asthma prior to death.ObjectiveWe performed an economic analysis to describe the costs during 12 and 24 months prior to asthma death between 2013 and 2017 in France.MethodsAn observational cohort study was established using the French national health insurance database. Direct medical and non-medical costs, as well as costs related to absence from the workplace, were included in the analysis.ResultsIn total, 3,829 patients were included in the final analysis. Over 24 and 12 months prior to death, total medical costs per patient were €27,542 [26,545–28,641] and €16,815 [16,164–17,545], respectively. Total medical costs clearly increased over 24 months prior to death. Over 12 months prior to death, costs increased significantly according to age categories, with mean total costs of €8,592, €15,038, and €17,845, respectively, for the categories ConclusionTo conclude, the economic burden of asthma death is high and increases with time, age, and SABA dispensation.</p

Flowchart illustrating the trials selection.

<p>*8 duplicates in the search of unpublished RCTs.</p

Risk of cancers assessed by the modified intention to treat model and by the per protocol model.

<p>Abbreviations: mITT, modified intention to treat; NDA, New drug Approval; NMSC, non-melanoma skin cancers; OR, odds ratio; 95% CI, 95% confidence interval;</p>*<p>14 trials included for overall cancer analysis.</p>†<p>7 trials included for overall cancer analysis.</p>‡<p>The trial by Miyasaka <i>et al</i>. was excluded from these analyses for the two cancers that occurred in the placebo arm were not otherwise specified.</p>§<p>These analyses excluded two trials: the one by Miyasaka <i>et al</i>. (because the two cancers that occurred in the placebo arm were not otherwise specified) and the one by Weisman <i>et al.</i> (because the three skin cancers that occurred were not otherwise specified).</p>¶<p>Publication bias.</p