Background No head-to-head clinical trials have been published comparing aflibercept and bevacizumab for the neovascular form of age-related macular degeneration (AMD). Adjusted indirect comparisons may provide useful information on the relative efficacy of competing interventions. Purpose To compare the efficacy of aflibercept and bevacizumab for the treatment of wet AMD using an adjusted indirect comparison. Materials and methods PubMed was searched for randomised controlled trials (RCTs) comparing aflibercept or bevacizumab with ranibizumab. Selection criteria were: 1) phase III RCTs; 2) intravitreal aflibercept 2.0 mg (every two months after three consecutive monthly doses) versus monthly intravitreal ranibizumab 0.5 mg; 3) monthly intravitreal ranibizumab 0.50 mg versus monthly intravitreal bevacizumab 1.25 mg; 4) patients included with active choroidal neovascularisation secondary to AMD and 5) similar duration and methodology. A meta-analysis of RTCs comparing aflibercept versus ranibizumab and bevacizumab versus ranibizumab was performed. Odds ratios and 95% confidence intervals for dichotomous data were calculated by Mantel-Haenszel’s method. An adjusted indirect comparison by Bucher’s method using the ITC software from Canadian Agency for Drug Technologies in Health was done, with ranibizumab as a common comparator. The endpoint was the proportion of patients who improved by ≥15 ETDRs letters at 52 weeks. Results Two RCTs comparing aflibercept with ranibizumab (VIEW-1 and VIEW-2) and two RTCs comparing bevacizumab versus ranibizumab (CATT-1 and CATT-2) met the inclusion criteria. Meta-analysis showed no significant difference between aflibercept and ranibizumab (ARR:1.50% [-3.79 to 6.73]) or bevacizumab and ranibizumab (ARR: 20% [-9.0 to 4.0]). The adjusted indirect comparison didn’t show a statistically significant difference between aflibercept and bevacizumab (ARR: 3.0% [-4.90 to 10.90]). Conclusions Notwithstanding the limitations of an adjusted indirect comparison, no significant differences were found between aflibercept and bevacizumab in AMD. Until head-to head trials are available, adjusted indirect comparisons based on trial data could be relevant to guide therapeutic choices. No conflict of interest.

BackgroundAppropriate, accurate and timely distribution of medicines to patients is a pharmacist’s responsibility. Automated dispensing cabinets (ADCs) improve efficiency in distribution; but patient safety may be compromised if they are used incorrectly.PurposeTo analyse pharmaceutical interventions in ADC dispensing, in order to adopt steps that improve patient safety.Material and methodsA descriptive study was conducted in a 470-bed specialist hospital. Over 8 months (April–December 2013) pharmaceutical interventions in drugs dispensing to 9 infirmary units with ADC were collected. Interventions were made and recorded during ADC drug replacement in hospital wards, or during incident resolution at the pharmacy cabinet control point. All interventions made during the study period were analysed to determine their category and frequency. Interventions were recorded according Hernández and Poveda’s classification of medicines errors in ADC.Results290 interventions were collected. The most frequent type of intervention was that related to incorrect ADC procedures and handling (59.7%). In this category, interventions were due to stock discrepancies (79), medicine devolutions discrepancies (35), lack of concordance with opiate stocks (25), wrong medicine location (17), and drug load (17). Another category identified was intervention related to the structure and functioning of the ADC (29.3%), and includes the following events: door blockage (29), drawer break/obstruction (14), other mechanical structural fault (19), mistakes in the ADC-hospital census connection (8), system breakdown (7), refrigerator failure (7) and electric supply failure (1). The less frequent intervention categories were those related to inappropriate handling and storage (11.0%), and included interventions caused by expired medicines (15), lack of opiate prescriptions (6), damaged medicines (3), cabinet start-up (1), quarantine drug unload (19), and other reasons (6).ConclusionThe most common interventions on automated dispensation process are related to handling of cabinets. Therefore it’s necessary to remind nurses periodically that correct handling of ADCs is essential to guarantee medicine availability and optimal storage, both necessary for safe drug use.References and/or acknowledgementsNo conflict of interest.

BackgroundBiological treatments are responsible for numerous side effects, some of which can trigger a medical consultation by the patient in primary care. When these drugs are prescribed and dispensed, the process is not reflected in the patient’s records so the primary care physician does not know which patients are treated with these drugs.PurposeTo describe the impact of a care model that puts alerts in electronic records to enable primary care physicians to identify rheumatology patients on biological treatment and their associated adverse reactions.Material and methodsA retrospective observational study of patients from the Rheumatology Unit on biological treatment and analysis of the most frequent adverse reactions produced by these drugs that could cause a consultation in primary care. The study period was one year (October 2013–September 2014). A search of adverse events classified as very common (≥1/10 patients) of each drug and the number of patients identified in the APD-ATHOS program was conducted.ResultsA total of 7 drugs was identified and 461 patients were treated. The most-used drugs were etanercept (N = 209, 45.3%) and adalimumab (N = 172, 37.3%). Adverse reactions that would have had a higher frequency of occurrence and could generate a consultation in primary care were: respiratory tract infections (N = 48, 10.4%), hypercholesterolemia (N = 22.5, 4.9%), headache (N = 20, 4.3%), leukopenia (N = 17.2, 3.7%), nausea (N = 17.2, 3.7%), rash (N = 17.2, 3.7%), musculoskeletal pain (N = 17.2, 3.7%), increased liver enzymes (N = 3.9, 0.8%). A total of 163 patients might present one of these adverse reactions.ConclusionA high number of patients could benefit from alerts, as they provide primary care professionals with relevant information about common adverse events.ReferenceGutiérrez Fernández D, Foncubierta Fernández A, Anguita Carazo JL. Adalimumab desensitization protocol in a patient with a generalized urticarial reaction and angioedema following adalimumab administration. J Investig Allergol Clin Immunol 2014;24(4):273–5No conflict of interest.

BackgroundFollowing the introduction of a new iodine-containing contrast medium (IC) (iomeprol) to our hospital formulary, an unexpected increase in adverse drug reactions (ADRs) to the IC was observed. Consequently, a root cause analysis (RCA) was made to identify the causes of adverse events, and to suggest improvements to prevent recurrences.PurposeTo determine the corrective measures resulting from an RCA to investigate the unexpected increase in ADRs associated with the introduction of a new IC (iomeprol) in the hospital, and to evaluate the effectiveness of measures implemented.Material and methodsThe study was made in a 460-bed specialty hospital. The RCA multidisciplinary team was composed of medical and nursing directors and supervisors of radiology and pharmacy units. Steps followed in RCA involve: 1-problem description and data collection, 2-organisational system analysis, 3-human factor analysis, 4-team and material management analysis, 5-patient-related factors analysis, 6-RCA team proposal. The monthly number of ADRs notified before and after RCA was used to assess the effectiveness of corrective measures. Notifications of IC ADRs were extracted from the records of yellow card reports, as well as patient data, drug data and ADR data.ResultsProposals generated by RCA were: 1-to retrain radiology technicians and doctors on the use of IC pumps for administration, 2-to inspect pump calibration, 3-to verify the premedication needed. In the period 2009–2012 average notification of IC ADRs was 0.87/month. Since iomeprol was introduced in 2013/03 until RCA was performed (2013/05/08) 9 notifications were recorded (6/month); type and severity were similar to the previous period. Retraining and pump calibration inspection were finalised in June. The average IC ADR notification rate in the period July–December 2013 was 1.67/month. In the period January–October 2014, the notification rate was 0.89/month, similar to that before introduction of the new IC.Conclusion1. Technical training, machine calibration and patient evaluation were identified by RCA as aspects to improve. 2. After corrective measures had been taken, IC RCA notification has returned to the usual value.References and/or acknowledgementsNo conflict of interest.

BackgroundTyrosine Kinase Inhibitors (TKIs) are drugs that cause significant adverse reactions and interactions in patients. Prescription and dispensing of TKIs both take place in Hospital Pharmacies. Primary Care physicians (GPs) do not have very much information about either these drugs or patients on TKI treatment.PurposeTo describe a model for giving advice with recommendations about interactions and adverse reactions of TKIs, to provide support and information for PC physicians.Material and methodsPatients on TKI treatment were identified by the APD-ATHOS Prisma and Oncofarm software. The databases were searched for adverse reactions and interactions due to TKIs, together with their management. We selected the most common adverse reactions and interactions, including those that could cause the patients to consult their general practitioner. Then, we made a document with all the information and PC pharmacists established a link between this document and the Electronic Clinical History of each patient to enable GPs to identify patients who were on TKI treatment and also recommendations about their management.Results44 patients were identified (37 with imatinib, 4 with dasatinib and 3 with nilotinib). 29 adverse reactions were found (9 common to all 3 TKIs, plus 8 with dasatinib, 8 with nilotinib and 4 with imatinib). Interactions were classified into: drugs that increase or reduce the effects of TKIs and drugs whose effects and toxicity are increased or decreased by TKIs. The most significant interactions were: imatinib-simvastatin, imatinib-acetaminophen, imatinib-ibuprofen; nilotinib/dasatinib-proton pump inhibitors, nilotinib/dasatinib-histamine-2 receptor antagonists, nilotinib/dasatinib-drugs that prolong the QT interval, nilotinib/dasatinib-oral anticoagulants and dasatinib-food.ConclusionThe way of giving advice should help GPs to identify and manage frequent adverse reactions and interactions of TKIs. This process will be repeated for other oral anti-cancer drugs. Further studies are necessary to confirm the usefulness of this tool.References and/or acknowledgementsNo conflict of interest.