Diogo Mendes

Nurses' spontaneous reporting of adverse drug reactions: expert review of routine reports.

AIM The aims of this study were to analyse spontaneously reported adverse drug reactions according to their previous description, seriousness, causality and the reporting professional. BACKGROUND Previous findings showed that fewer nurses than physicians and pharmacists report adverse drug reactions. This is not attributed to any lack of ability in identifying adverse drug reactions. METHOD Adverse drug reactions received by the Central Portugal Regional Pharmacovigilance Unit, between 2001 and 2011, were studied. Certain and probable adverse drug reactions were included to test differences between professional groups for serious and non-serious adverse drug reactions. RESULTS The Central Portugal Regional Pharmacovigilance Unit received 1014 adverse drug reactions. Fifty-four nurses reported 66 adverse drug reactions, whereas 232 physicians and 145 pharmacists reported 589 and 357 adverse drug reactions, respectively. Considering the number of practising professionals, it was estimated that 0.55% of nurses, 3.96% of physicians and 7.08% of pharmacists have reported an adverse drug reaction. Of the 633 adverse drug reactions assessed as certain or probable, 46 (21 serious), 387 (192 serious) and 198 (77 serious) were reported from nurses, physicians and pharmacists, respectively. There were no differences in the reporting of serious adverse drug reactions among nurses, physicians and pharmacists. CONCLUSIONS Nurses are able to identify serious adverse drug reactions although they report less than other professionals. IMPLICATIONS FOR NURSING MANAGEMENT Nurses need to increase their involvement in spontaneous reporting schemes by taking responsibility for routinely reporting suspected adverse drug reactions.

Safety profiles of adalimumab, etanercept and infliximab: a pharmacovigilance study using a measure of disproportionality in a database of spontaneously reported adverse events

Despite being effective, the biologics approved for treating rheumatoid arthritis have been associated with serious adverse events. This study is aimed at comparing the safety profiles of adalimumab, etanercept and infliximab by analysing the disproportionalities of the associations between the different adverse events and the different biologics in the Portuguese spontaneous reporting database.

Number needed to harm in the post-marketing safety evaluation: results for rosiglitazone and pioglitazone.

Our aim is to investigate the usefulness of metric indices in post‐marketing safety evaluations by estimating number needed to harm (NNH) values for cardiovascular (CV) adverse outcomes for rosiglitazone and pioglitazone.

Testing the usefulness of the number needed to treat to be harmed (NNTH) in benefit-risk evaluations: case study with medicines withdrawn from the European market due to safety reasons

ABSTRACT Objective: To explore the usefulness of number needed to treat to be harmed (NNTH), in benefit-risk assessments, by studying the agreement between NNTH values and withdrawals of medicines from European market due to safety reasons. Methods: Medicines with data from longitudinal studies were included. Studies were identified from European Medicines Agency’s Reports. Meta-analyses were performed to pool odds ratios (OR) with 95% confidence-intervals (CI). Published control event rates were applied to ORs to calculate NNTHs (95%CI) for selected adverse events. Results: NNTH (95%CI) decreased from pre- to post-marketing for the eight medicines included: peripheral neuropathy (∞ vs. 12[non-significant; NS] with almitrine; heart valve disease with benfluorex (∞ vs. NNTH ranging from 7[4–13] to 7[5–9]); myopathy (−4096[NS] vs. 797[421–1690]), new-onset diabetes (113[NS] vs. 390[425–778]), bleeding (∞ vs. 517[317–1153]), and infection (∞ vs. 253[164–463]) with niacin-laropiprant; psychiatric disorders (12[7–34] vs. 9[5–24]) with rimonabant; myocardial infarction (MI) [−1305 vs. 270[89–4362]) with rofecoxib; MI (−510 vs. NNTH ranging from 152[55–4003] to 568[344–1350]) with rosiglitazone; cardiovascular events (∞ vs. 245[129–1318]) with sibutramine; and liver injury (∞ vs. 5957[NS]) with ximelagatran. Conclusion: NNTH have potential of use as a supportive tool in benefit-risk re-evaluations of medicines and may help regulators to making decisions on drug safety.

A systematic review of observational studies evaluating costs of adverse drug reactions

Introduction The growing evidence of the increased frequency and severity of adverse drug events (ADEs), besides the negative impact on patient’s health status, indicates that costs due to ADEs may be steadily rising. Observational studies are an important tool in pharmacovigilance. Despite these studies being more susceptible to bias than experimental designs, they are more competent in assessing ADEs and their associated costs. Objective To identify and characterize the best available evidence on ADE-associated costs. Methods MEDLINE, Cochrane Library, and Embase were searched from 1995 to 2015. Observational studies were included. The methodological quality of selected studies was assessed by Cochrane Collaboration tool for experimental and observational studies. Studies were classified according to the setting analyzed in “ambulatory”, “hospital”, or both. Costs were classified as “direct” and “indirect”. Data were analyzed using descriptive statistics. The total incremental cost per patient with ADE was estimated. Results Twenty-nine (94%) longitudinal observational studies and two (7%) cross-sectional studies were included. Twenty-three (74%) studies were assessed with the highest methodological quality score. The studies were mainly conducted in the US (61%). Twenty (65%) studies evaluated any therapeutic group. Twenty (65%) studies estimated costs of ADEs leading to or prolonging hospitalization. The “direct costs” were evaluated in all studies, whereas only two (7%) also estimated the “indirect costs”. The “direct costs” in ambulatory ranged from €702.21 to €40,273.08, and the in hospital from €943.40 to €7,192.36. Discussion Methodological heterogeneities were identified among the included studies, such as design, type of ADEs, suspected drugs, and type and structure of costs. Despite such discrepancies, the financial burden associated with ADE costs was found to be high. In the light of the present findings, validated methods to measure ADE-associated costs need future research efforts.

A systematic review and meta-analysis of the association between systemic fluoroquinolones and retinal detachment

Several pharmacoepidemiologic studies have been carried out evaluating the risk of retinal detachment associated with systemic fluoroquinolones. This meta‐analysis aims to investigate such association, in the light of the best scientific evidence available.

Risk of Ophthalmic Adverse Effects in Patients Treated with MEK Inhibitors: A Systematic Review and Meta-Analysis

Objectives: This meta-analysis aims to evaluate the risk of ophthalmic adverse effects associated with MEK inhibitors. Methods: A literature search was conducted in PubMed and the Cochrane Library to identify randomized clinical trials (RCTs) which have been designed to evaluate the efficacy and safety of MEK inhibitors. Overall risk of ophthalmic adverse effects, chorioretinopathy, retinal detachment, blurred vision, uveitis, and eye haemorrhage were the assessed outcomes. Peto odds ratios (ORs) with their 95% confidence intervals (CIs) were pooled. Between-study heterogeneity was assessed using I2 statistics. Results: Thirteen RCTs were included in this meta-analysis. Overall, MEK inhibitors were associated with an increased risk of ophthalmic adverse effects (OR 2.24; 95% CI 1.75-2.87; p < 0.0001; I2 = 86.5%). An increased risk was also estimated for chorioretinopathy (OR 5.44; 95% CI 2.89-10.23; p < 0.0001; I2 = 0%), retinal detachment (OR 6.54; 95% CI 3.28-13.03; p < 0.0001; I2 = 0%), and blurred vision (OR 2.30; 95% CI 1.50-3.54; p < 0.0001; I2 = 60.1%), but not for uveitis (OR 0.99; 95% CI 0.14-7.03; p = 0.991; I2 = 2.9%) or eye haemorrhage (OR 0.72; 95% CI 0.04-12.39; p = 0.824; I2 = 29.8%). Conclusions: Treatment with MEK inhibitors seems to increase the risk of ophthalmic adverse effects. A need for monitoring the safety of this class of drugs exists. Regulators, clinicians, and other health care professionals must, together, be involved in this process.

Number needed to treat (NNT) in clinical literature: an appraisal

BackgroundThe number needed to treat (NNT) is an absolute effect measure that has been used to assess beneficial and harmful effects of medical interventions. Several methods can be used to calculate NNTs, and they should be applied depending on the different study characteristics, such as the design and type of variable used to measure outcomes. Whether or not the most recommended methods have been applied to calculate NNTs in studies published in the medical literature is yet to be determined. The aim of this study is to assess whether the methods used to calculate NNTs in studies published in medical journals are in line with basic methodological recommendations.MethodsThe top 25 high-impact factor journals in the “General and/or Internal Medicine” category were screened to identify studies assessing pharmacological interventions and reporting NNTs. Studies were categorized according to their design and the type of variables. NNTs were assessed for completeness (baseline risk, time horizon, and confidence intervals [CIs]). The methods used for calculating NNTs in selected studies were compared to basic methodological recommendations published in the literature. Data were analyzed using descriptive statistics.ResultsThe search returned 138 citations, of which 51 were selected. Most were meta-analyses (n = 23, 45.1%), followed by clinical trials (n = 17, 33.3%), cohort (n = 9, 17.6%), and case–control studies (n = 2, 3.9%). Binary variables were more common (n = 41, 80.4%) than time-to-event (n = 10, 19.6%) outcomes. Twenty-six studies (51.0%) reported only NNT to benefit (NNTB), 14 (27.5%) reported both NNTB and NNT to harm (NNTH), and 11 (21.6%) reported only NNTH. Baseline risk (n = 37, 72.5%), time horizon (n = 38, 74.5%), and CI (n = 32, 62.7%) for NNTs were not always reported. Basic methodological recommendations to calculate NNTs were not followed in 15 studies (29.4%). The proportion of studies applying non-recommended methods was particularly high for meta-analyses (n = 13, 56.5%).ConclusionsA considerable proportion of studies, particularly meta-analyses, applied methods that are not in line with basic methodological recommendations. Despite their usefulness in assisting clinical decisions, NNTs are uninterpretable if incompletely reported, and they may be misleading if calculating methods are inadequate to study designs and variables under evaluation. Further research is needed to confirm the present findings.

Drug-induced hypersensitivity: A 5-year retrospective study in a hospital electronic health records database

Hypersensitivity adverse drug reactions (HADRs) are associated with considerable morbidity and mortality. The aim of this study was to identify cases of HADRs within a hospital electronic health records (EHR) database.