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Risk of ischemic stroke associated with non-steroidal anti- inflammatory drugs and paracetamol: a population-based case-control study

To assess the risk of non‐fatal ischemic stroke associated with non‐steroidal anti‐inflammatory drugs (NSAIDs) and paracetamol. The effects of dose, duration of treatment, background cardiovascular (CV) risk and use of concomitant aspirin were studied.

Vemurafenib-induced toxic epidermal necrolysis: possible cross-reactivity with other sulfonamide compounds.

Vemurafenib is a newly licensed target‐directed medication. It has been proven to improve the survival of patients with metastatic melanoma and the BRAFV600E mutation; however, adverse cutaneous reactions are frequent. Few cases of life‐threatening severe cutaneous adverse reactions (SCARs) induced by vemurafenib have been reported. Dabrafenib, another selective BRAF inhibitor, has been licensed recently as an alternative drug with the same indications. From a molecular point of view, both vemurafenib and dabrafenib contain a sulfonamide group; cross‐reactivity to sulfonamide compounds has been reported in allergic patients. We report on a patient with vemurafenib‐induced toxic epidermal necrolysis (TEN). In vitro analysis of lymphocyte reactivity to vemurafenib showed positive results, confirming drug causality. In addition, lymphocytes from the patient reacted to dabrafenib and to the antibiotic sulfonamide drug sulfamethoxazole. Moreover, lymphocytes from two patients with cutaneous adverse reactions to sulfamethoxazole also reacted to vemurafenib and dabrafenib in vitro. These data strongly suggest that there might be clinical cross‐reactivity between BRAF inhibitors and sulfonamides in some patients. Thus, precautions should be taken to avoid sulfonamide drugs as much as possible in patients showing serious hypersensitivity reactions to vemurafenib and vice versa.

Seasonal changes in prescribing of long-acting beta-2-agonists-containing drugs.

BACKGROUND For patients with asthma, COPD, or asthma-COPD overlap syndrome (ACOS), inter-country comparisons of seasonal changes in drug prescriptions are scarce or missing. Hence, we aimed to compare seasonal changes in prescription rates of long-acting beta-2-agonist (LABA) in four European countries. METHODS A common study protocol was applied to six health care databases (Germany, Spain, the Netherlands (2), and the UK (2)) to calculate age- and sex-standardized point prevalence rates (PPRs) of LABA-containing prescriptions by the 1st of March, June, September, and December of each year during the study period 2002-2009. Seasonal variation of PPRs was quantified using seasonal indexes (SIs; based on the ratio-to-moving-average-method) and SIs averaged over the study period (aSI) stratified by sex, age, and indication (asthma, COPD, or ACOS). RESULTS There was a moderate seasonal change in LABA-containing prescriptions which was more pronounced in asthma or COPD patients compared to ACOS patients. For asthma and ACOS patients, highest seasonal variation was found for patients living in Spain (aSI: 87.3-110.7, aSI: 93.2-103.1) whereas for COPD highest seasonal variation was revealed for the NPCRD database (the Netherlands) (aSI: 92.2-105.6). Regarding age and sex, highest seasonal variation was found in Spanish boys under 10 years of age having a diagnosis of asthma. CONCLUSIONS By applying a common analysis in six databases, we could observe moderate overall seasonal changes in LABA-containing prescription rates in patients with asthma, COPD, or ACOS.

Care in patients with epidermal necrolysis in burn units. A nursing perspective

OBJECTIVE To describe how nursing care is delivered to patients with epidermal necrolysis in burn units/specialized units in Spain and a selection of countries. METHOD Descriptive cross-sectional study. Data were collected through a structured questionnaire which was sent to nurse managers in all burn units in Spain and a selection of countries. Descriptive statistics was used to summarize the results. RESULTS All BU/SUs in Spain (n=12) and seven BU/SUs from a selection of countries completed the questionnaire. A lack of specific nursing protocols on Epidermal Necrolysis was observed in most burn units in Spain. Skin cleansing techniques such as showering were only reported by participants from Spain. Use of antiseptics was less frequent in other countries. Conservative skin management was the most extended practice reported by all participants. The use of vaginal molds to prevent synechiae and coverage of the ocular surface with amniotic membrane to minimize sequelae were rarely reported. Pain assessment was not always documented in sedated patients and few participants reported the use of specific scales for this purpose. All nurses agreed in the need for consensus nursing care guidelines on the disease. CONCLUSIONS Nursing care in patients with epidermal necrolysis varied between burn units in Spain. Differences and similarities were observed when compared with burn units in other countries. Genital and ocular care were outdated in all BU/SUs. Pain assessment documentation was suboptimal. Evidence-based nursing care guidelines were generally demanded by all participants to help reduce mortality and morbidity of this rare and often devastating disease.

Approach to Severe Cutaneous Adverse Drug Reactions

Opinion StatementSevere cutaneous adverse drug reactions (SCARs) can occur at any age and can be life threatening, although some drugs have been more frequently reported than others. The spectrum of SCARs includes acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, also known as drug-induced hypersensitivity syndrome (DiHS) or hypersensitivity syndrome (HSS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Immediate withdrawal of the offending drug is the mainstay treatment in SCARs, and rechallenge often leads to recurrent reactions. Cross reactivity and multiple sensitivities have also been reported. The identification of the offending medication at the onset of the disease is therefore essential to avoid future exposures to the same or chemically related compounds. Various algorithms can be useful to identify the culprit drug in the acute stage. Delayed onset from the initiation of treatment differs in the various clinical entities. Therefore, a prompt, accurate diagnosis is crucial for proper identification of the offending agent. After resolution of the disease, cutaneous tests and in vitro tests can be useful for confirmation of drug causality and investigation of possible cross-reactivity. SCARs are rare diseases, given the incidence is extremely low. Multidisciplinary and international teams are required to study these diseases. Further research is needed to fully understand etiopathogenesis and for the development of specific treatments.