BackgroundPharmacovigilance uses data mining algorithms on spontaneous reporting databases to assess significant associations between adverse drug reactions (ADR) and drugs. These pharmacovigilance databases provide early warnings of hazards that were missed before marketing a drug, mainly because of the limitations of clinical trials. In July 2013, tetrazepam marketing was suspended, after four decades on the market, due to serious skin and subcutaneous tissue disorders (SSTD-ADR).PurposeTo detect possible pharmacovigilance signals between SSTD-ADR and benzodiazepines, by applying data mining on the American Pharmacovigilance Database (FAERS) whose data were public.Material and methodsWe calculated data mining algorithms (PRR: proportional reporting ratio; ROR: reporting odds ratio; IC: information component, and EBGM: empiric Bayesian geometric mean) on spontaneous reports of SSTD-ADR due to benzodiazepines commercialised in the USA, registered in FAERS. All statistical algorithms were calculated from 2 × 2 contingency tables, according to the literature: PRR–1.96 SE (standard error) (with χ2 and p value associated), ROR–1.96 SE, IC–2 SD (standard deviation) and EBGM–2 SD precision algorithms were calculated. A signal was considered when: PRR ≥2 (with χ2 value ≥4); lower band of 95% two sided confidence interval (95% CI) of ROR >1; 95% CI two sided of IC >0; or 95% CI one sided of EBGM ≥2. All calculations were done using Excel 2011 14.4.1.ResultsWe found 3957 SSTD-ADR (3.05% of all benzodiazepine ADR reports). ROR yielded signals for 8 drugs (clobazam, clonazepam, clorazepate, midazolam, oxazepam, quazepam, tetrazepam and triazolam), PRR and IC for 4 (clobazam, midazolam, quazepam and tretrazepam), while EBGM detected only a signal for tetrazepam.Midazolam, clobazam and quazepam originated a signal by 3 algorithms. Tetrazepam was the only one which generated a signal by 4 algorithms. Clobazam originated a signal for Stevens-Johnson Syndrome and Blister; midazolam for toxic epidermal necrolysis, DRESS Syndrome and erythema; quazepam for erythema multiform and drug eruption; and tetrazepam for dermatitis bullous, toxic skin eruption, rash maculopapular and rash erythematous. (All of these terms are ‘preferred term’ level of the MedDRA classification).ConclusionOur pharmacovigilance data mining revealed the existence of potential signals for benzodiazepine and SSTD-ADR. However, to establish causality, larger studies providing new clinical evaluation on these associations will be required.No conflict of interest.

BackgroundIn July 2013, the European Medicines Agency suspended the marketing authorisation of tetrazepam across the European Union due to serious cutaneous adverse drug reactions (ADR). Here we examine information described in PubMed and reported to the main pharmacovigilance databases (PhDB) related to ADR associated with tetrazepam.PurposeTo ascertain the described evidence on cutaneous ADR due to tetrazepam, which could lead to the end of commercialisation of this drug that has been on the market for more than 40 years.Material and methodsFirst, we conducted a search in MEDLINE and Cochrane (January 2015) on ADR due to tetrazepam, in peer reviewed journals. Inclusion criteria were: studies performed on humans or tetrazepam induced ADR case reports. Second, we collected data on spontaneous reporting of suspected ADR due to tetrazepam, from 1989 until December 2014, from the main PhDB: Spanish (FEDRA), French (BNPV) and American (FAERS).Results30 manuscripts were included in our systematic review, which encompassed data from 72 subjects, all suffering from some form of cutaneous ADR related to tetrazepam (100%). No other ADR were found. The most frequent ADR described were: airborne contact dermatitis (26 cases), maculopapular exanthema (17 cases), toxic epidermal necrolysis (5 cases, 1 patient died) and erythema multiforme (5 cases).Additionally, we identified 3481 tetrazepam associated ADR in PhDB (924 from FEDRA, 1616 from BNPV and 941 from FAERS). Of them, cutaneous ADR were the most reported ADR (32.0% in FEDRA, 49.8% in BNPV and 12.7% in FAERS). PhDB included other tetrazepam associated ADR: neurological (12.5%), gastrointestinal (7.7%), psychiatric (5.7%) and other. Regarding cutaneous ADR in all PhDB, the most frequent severe events described were: erythema multiform (59 cases, 1 with a fatal outcome), Stevens-Johnson syndrome (33 cases, 1 with lethal evolution), Lyell syndrome (33 cases notified, 9 fatal outcomes) and DRESS syndrome (15 cases).ConclusionOur study revealed discrepancies in the information provided by these two different sources, both in the number of reported cases as well as in the type of ADR reported. We stress the importance of better communication of knowledge between the scientific literature and pharmacovigilance agencies, to prevent the use of marketed drugs with well established side effects over long periods.No conflict of interest.

BackgroundManagement of catheter related infections (CRIs) depends on the severity, type of catheter and need to keep it. When it is documented, systemic antimicrobial therapy should be started, as antibiotics lock therapy if the central venous catheter (CVC) is not removed. We reviewed the management of CRIs in patients undergoing haemodialysis over 2 years and found that only 18.7% of patients were properly handled. We decided to develop a treatment protocol for this type of infections with the nephrology department.PurposeTo analyse changes in the management of CRIs in patients undergoing haemodialysis after implantation of a management protocol.Material and methodsAn observational and retrospective study was carried out over 6 months in patients undergoing haemodialysis in which intravenous antibiotic therapy was initiated after implementation of a CRI management protocol. The results were compared with the results obtained in a previous study on the implementation of this protocol. The following variables were recorded: sex, age, type of venous access, type of extracted sample (blood cultures, exudate catheter or other sample), microorganisms isolated, intravenous antibiotics used and antibiotic lock therapy in patients with CVC.Results24 requests for intravenous antibiotics for 18 patients were analysed. 66.6% were men, median age 68.9 years and 61.1% of patients had CVC. Blood culture samples were collected in 50% of patients and other samples obtained were urine culture (20.8%), wound exudates (20.8%) and catheter exit site exudates (12.5%). There was no catheter related bacteraemia because all blood cultures were negative. There were 10 positive results for the rest of the samples and Pseudomonas aeruginosa was the most common isolate (50%) followed by coagulase negative staphylococcus (20%). The most common treatment was vancomycin monotherapy (25%), followed by ceftazidime monotherapy (20.8%), a combination of both drugs (16.7%) and gentamicin (12.5%). Antibiotic lock therapy was performed in 70.8% of patients with CVC. Also, 12 pharmaceutical interventions about antibiotic selection, treatment duration or suspension because of negative results were made, and 66.7% were accepted.ConclusionResults have improved after implementation of a CRI management protocol, particularly antibiotic lock therapy (from 18.7% to 70.8%), although it is still necessary to reinforce the need for taking blood cultures in serious infection to discard CRIs.No conflict of interest

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BackgroundSome complications described with enteral nutrition (EN) administration are metabolic and electrolyte disturbances.PurposeTo review glycaemic, renal and electrolyte alterations in patients receiving EN as exclusive diet.Material and methodsAll patients admitted except those hospitalised in the Intensive Care Unit who received EN during the study period (January to March 2017) were retrospectively reviewed using the Farmatools prescription program. Only those who covered at least 75% of their requirements (calculated using Harris Benedict equation and taking into account the stress factor) along this route and who received at least 5 days of EN were included.Variables registered, before beginning EN and after 5 days of treatment were: glycaemia, serum creatinine, serum sodium and potassium, and GOT and GPT values. Hyperglycaemia was considered as an increase with respect to baseline glucose of at least 20%, and altered creatinine as increase by at least 30%, both of them with a value above the recommended range.ResultsDuring the study period, 45 patients received EN and 21 (46.7%) covered 75% of their requirements. 57.1% were males and 42.9% females, with a mean age of 72.6 years.Of the total number of patients evaluated, five presented hyperglycaemia (8.9%), one hyperkalaemia (2.2%), two GOT elevation (4.4%) and four GPT elevations (8.8%). None of them presented creatinine value elevation.ConclusionIt is necessary to carry out a greater nutritional follow-up to patients admitted to our hospital who receive EN because half of them do not have their nutritional requirements covered. We have not detected significant alterations in the glycaemic, electrolytic and renal results, which is a reason why EN can be considered a safe type of nutritional support from the metabolic and electrolytic point of view.No conflict of interest