Projecte d'integració entre SAP GH - SAP MM - Kàrdex

Projecte d'integració entre dos sistemes SAP (gestió hospitalària i gestió de materials) amb un altre sistema aliè a SAP, el sistema de magatzem de medicaments Kàrdex, mitjançant comunicacions via SAP Process Integration.

Selected ABCB1, ABCB4 and ABCC2 Polymorphisms Do Not Enhance the Risk of Drug-Induced Hepatotoxicity in a Spanish Cohort.

BACKGROUND AND AIMS Flawed ABC transporter functions may contribute to increased risk of drug-induced liver injury (DILI). We aimed to analyse the influence of genetic variations in ABC transporters on the risk of DILI development and clinical presentations in a large Spanish DILI cohort. METHODS A total of ten polymorphisms in ABCB1 (1236T>C, 2677G>T,A, 3435T>C), ABCB4 (1954A>G) and ABCC2 (-1774G>del, -1549A>G, -24C>T, 1249G>A, 3972C>T and 4544G>A) were genotyped using Taqman 5' allelic discrimination assays or sequencing in 141 Spanish DILI patients and 161 controls. The influence of specific genotypes, alleles and haplotypes on the risk of DILI development and clinical presentations was analysed. RESULTS None of the individual polymorphisms or haplotypes was found to be associated with DILI development. Carriers homozygous for the ABCC2 -1774del allele were however only found in DILI patients. Hence, this genotype could potentially be associated with increased risk, though its low frequency in our Spanish cohort prevented a final conclusion. Furthermore, carriers homozygous for the ABCC2 -1774G/-1549A/-24T/1249G/3972T/4544G haplotype were found to have a higher propensity for total bilirubin elevations when developing DILI. CONCLUSIONS Our findings do not support a role for the analysed polymorphisms in the ABCB1, ABCB4 and ABCC2 transporter genes in DILI development in Spanish patients. The ABCC2 -1774deldel genotype was however restricted to DILI cases and could potentially contribute to enhanced DILI susceptibility.

Drug assessment by a Pharmacy and Therapeutics committee: from drug selection criteria to use in clinical practice.

BACKGROUND In Spain, hospital medicines are assessed and selected by local Pharmacy and Therapeutics committees (PTCs). Of all the drugs assessed, cancer drugs are particularly important because of their budgetary impact and the sometimes arguable added value with respect to existing alternatives. This study analyzed the PTC drug selection process and the main objective was to evaluate the degree of compliance of prescriptions for oncology drugs with their criteria for use. METHODS This was a retrospective observational study (May 2007 to April 2010) of PTC-assessed drugs. The variables measured to describe the committee's activity were number of drugs assessed per year and number of drugs included in any of these settings: without restrictions, with criteria for use, and not included in formulary. These drugs were also analyzed by therapeutic group. To assess the degree of compliance of prescriptions, a score was calculated to determine whether prescriptions for bevacizumab, cetuximab, trastuzumab, and bortezomib were issued in accordance with PTC drug use criteria. RESULTS The PTC received requests for inclusion of 40 drugs, of which 32 were included in the hospital formulary (80.0%). Criteria for use were established for 28 (87.5%) of the drugs included. In total, 293 patients were treated with the four cancer drugs in eight different therapeutic indications. The average prescription compliance scores were as follows: bevacizumab, 83% for metastatic colorectal cancer, 100% for metastatic breast cancer, and 82.3% for non-small-cell lung cancer; cetuximab, 62.0% for colorectal cancer and 50% for head and neck cancer; trastuzumab, 95.1% for early breast cancer and 82.4% for metastatic breast cancer; and bortezomib, 63.7% for multiple myeloma. CONCLUSION The degree of compliance with criteria for use of cancer drugs was reasonably high. PTC functions need to be changed so that they can carry out more innovative tasks, such as monitoring conditions for drug use.

Adecuación de la medicación cardiovascular en los diabéticos tipo 2 de Torrejoncillo (Cáceres) según los criterios STOP/STAR.

Financiación Proyecto de Investigación DIAB06/2012 «Detección y control de factores de riesgo y complicaciones vasculares en los pacientes diabéticos de la zona de salud de Torrejoncillo(Cáceres)». Fundación para la Formación y la Investigación de los Profesionales de Salud de Extremadura.

Guía farmacoterapéutica de hospital : Sistema Sanitario Público de Andalucía 2014

Actualización enero de 2015. Esta guía se ha realizado en virtud de un convenio de colaboración entre el Servicio Andaluz de Salud y la Sociedad Andaluza de Famacéuticos de Hospital. Grupo hospitalario para la evaluación de medicamentos en Andalucía (GHEMA).

Lipid changes in HIV-patients switching to the coformulated single tablet FTC/RPV/TDF (Eviplera®). Efficacy and safety analysis. GeSida Study 8114.

INTRODUCTION Rilpivirine (RPV) has a better lipid profile than efavirenz (EFV) in naïve patients (1). Switching to RPV may be convenient for many patients, while maintaining a good immunovirological control (2). The aim of this study was to analyze lipid changes in HIV-patients at 24 weeks after switching to Eviplera® (emtricitabine/RPV/tenofovir disoproxil fumarate [FTC/RPV/TDF]). MATERIALS AND METHODS Retrospective, multicentre study of a cohort of asymptomatic HIV-patients who switched from a regimen based on 2 nucleoside reverse transcriptase inhibitors (NRTI)+protease inhibitor (PI)/non nucleoside reverse transcriptase inhibitor (NNRTI) or ritonavir boosted PI monotherapy to Eviplera® during February-December, 2013; all had undetectable HIV viral load for ≥3 months prior to switching. Patients with previous failures on antiretroviral therapy (ART) including TDF and/or FTC/3TC, with genotype tests showing resistance to components of Eviplera®, or who had changed the third drug of the ART during the study period were excluded. Changes in lipid profile and cardiovascular risk (CVR), and efficacy and safety at 24 weeks were analyzed. RESULTS Among 305 patients included in the study, 298 were analyzed (7 cases were excluded due to lack of data). Men 81.2%, mean age 44.5 years, 75.8% of HIV sexually transmitted. 233 (78.2%) patients switched from a regimen based on 2 NRTI+NNRTI (90.5% EFV/FTC/TDF). The most frequent reasons for switching were central nervous system (CNS) adverse events (31.0%), convenience (27.6%) and metabolic disorders (23.2%). At this time, 293 patients have reached 24 weeks: 281 (95.9%) have continued Eviplera®, 6 stopped it (3 adverse events, 2 virologic failures, 1 discontinuation) and 6 have been lost to follow up. Lipid profiles of 283 cases were available at 24 weeks and mean (mg/dL) baseline vs 24 weeks are: total cholesterol (193 vs 169; p=0.0001), HDL-c (49 vs 45; p=0.0001), LDL-c (114 vs 103; p=0.001), tryglycerides (158 vs 115; p=0.0001), total cholesterol to HDL-c ratio (4.2 vs 4.1; p=0.3). CVR decreased (8.7 vs 7.5%; p= 0.0001). CD4 counts were similar to baseline (653 vs 674 cells/µL; p=0.08), and 274 (96.8%) patients maintained viral suppression. CONCLUSIONS At 24 weeks after switching to Eviplera®, lipid profile and CVR improved while maintaining a good immunovirological control. Most subjects switched to Eviplera® from a regimen based on NNRTI, mainly EFV/FTC/TDF. CNS adverse events, convenience and metabolic disorders were the most frequent reasons for switching.

Benzodiazepinas: riesgos y estrategias para su retirada

Benzodiazepines and hypnotic Z-drugs are indicated for the short-term treatment of insomnia and anxiety (4 weeks maximum) at the lowest dose possible. Despite the recommendations for short-term use and its unfavourable effects, the level of consumption of benzodiazepines in our context is high and it is continually rising. Prolonged medication usage is associated with adverse effects and significant risks, particularly in the elderly, and should, therefore, be avoided when approaching new treatment. If a previous treatment assessed is found to be inappropriate, its possible withdrawal must be considered. Benzodiazepines withdrawal is based on a gradual dose reduction and should be managed by establishing a doctor-patient relationship of trust to encourage and accomplish discontinuation.

Tratamiento farmacológico de la EPOC estable

Pharmacological treatment of patients with stable COPD should be individualised. Inhaled bronchodilators are the mainstay of pharmacological treatment for COPD. Long-acting medications (LABA or LAMA) are recommended over short-acting agents (SABA or SAMA). Short-acting bronchodilators are used on demand to rapidly control symptoms regardless of level of severity. Long-acting bronchodilators are used as maintenance therapy and are the mainstay of treatment in patients with permanent symptoms. Initial treatment for COPD is monotherapy with a long-acting bronchodilator. Clinical practice guidelines do not specify the best bronchodilator to use. The choice should be made on an individual basis, taking into account the patient’s preferences, response to treatment, its potential side effects and cost. When monotherapy fails to control symptoms, the first recommended step is to check medication adherence, inhaler technique and adequacy of inhalation device, and if these are correct but monotherapy is still insufficient, treatment should be intensified with combined inhaled therapies. Most clinical practice guidelines recommend the use of long-term therapy with LABA+inhaled corticosteroids in patients who experience frequent exacerbations and with FEV1 <50%. Long-term monotherapy with inhaled corticosteroids or oral corticosteroids is not recommended, and neither is the regular use of mucolytics nor the use of roflumilast.

Dapagliflozina

Dapagliflozin is a new oral antidiabetic agent whose mechanism of action increases renal glucose excretion, independently of insulin secretion or insulin action. The efficacy of dapagliflozin is dependent on renal function. The use of dapagliflozin has been licensed to improve glycaemic control in patients with type 2 diabetes mellitus as: - monotherapy when diet and exercise alone do not provide adequate glycaemic control in patients for whom the use of metformin is considered inappropriate due to intolerance. - Add-on combination therapy with other glucose-lowering agents including insulin, when these, together with diet and exercise, do not provide adequate glycaemic control. Funding has been restricted to the use of dapagliflozin, prior approval, as dual therapy in combination with metformin. This report aims to assess the efficacy and safety of dapagliflozin in the treatment of type 2 diabetes mellitus, rate the added therapeutic value of dapagliflozin in type 2 diabetes mellitus and identify its current place in therapy. A systematic literature search was carried out, for the purpose of this evaluation, using PubMed, Embase, Cochrane and IDIS databases as well as other secondary sources of evidence-based medicine, therapeutic bulletins and national and international drug agencies. Following the critical reading and analysis of the selected articles, a summary is made out of the scientific evidence available, using Scottish Intercollegiate Guidelines Network (SIGN) criteria. Only one randomised clinical trial, out of the ten trials found, was considered to be a suitable comparison (versus a dual therapy in combination with the sulfonylurea glipizide in patients inadequately controlled with metformin, diet and exercise). No trials have evaluated variables of relevance to patients, except for safety variables. The main efficacy variable in the trials was the change from baseline in HbA1c, except for a study which evaluated the change from baseline in total body weight as main variable. Baseline characteristics of the patients enrolled in the trials significantly differ from those of the population with diabetes in our society which tend to be of an older age and have a longer history of type 2 diabetes mellitus. The major limitation of dapagliflozin derives from its mechanism of action, since its efficacy decreases as renal function declines. The use of dapagliflozin is not recommended in patients with moderate to severe renal impairment ((CrCl<60ml/min or GFG <60 ml/min/1.73 m2) nor in elderly patients, in which a decrease in renal function can be expected. The assessment of safety includes the incidence and rate of discontinuations due to adverse events, episodes of hypoglycaemia, signs or symptoms of genital and urinary tract infections, dehydration, hypovolaemia and hypotension. Further pharmacoepidemiological studies are to be carried out to clarify the long-term effects of dapagliflozin on renal function and the potential effect in the development of breast and bladder tumours. Dapagliflozin as monotherapy has not been evaluated against adequate comparators (sulfonylureas, pioglitazone, gliptins). In combination therapy with metformin, the efficacy of dapagliflozin was shown to be non-inferior to glipizide plus metformin, resulting in a mean reduction of 0.52% in HbA1c, with a difference of 0.00 among both groups (95% CI: -0.11 a 0.11). There are no comparative data against other second-line treatment options. As shown in the studies, the overall incidence of adverse events with dapagliflozin as monotherapy (21.5%) was similar to that observed with placebo, and greater to that observed with metformin (15.4%). Hypoglycaemia of any type was the adverse event more frequently reported. The incidence of severe hypoglycaemic events observed in most of the studies was low. The overall incidence of adverse events observed in the study that compared dapagliflozin+metformin against glipizide+metformin was similar for both groups (27%) and incidence of hypoglycaemic events with dapagliflozin (3.5%) was significantly lower to that observed with glipizide (40.8%). Reductions of body weight of about 2 to 3 kg and a slight decrease in blood pressure (1 to 5 mmHg) have been observed in all studies in the groups treated with dapagliflozin together with diet and exercise. Dosing scheme (every 24 hours) is similar to other oral antidiabetic agents and its cost is similar to that for gliptines and higher to that for sulfonylureas or generic pioglitazone. Funding has been limited to the use of dapagliflozin as dual therapy regimen in combination with metformin as an option for patients with contraindication or intolerance to sulfonylureas, such a those experiencing frequent hypoglycaemic events, weight loss associated risks, as long as they are under 75 years of age and have no moderate to severe renal impairment. In the light of the above, we consider dapagliflozin means no therapeutic innovation in the therapy of type 2 diabetes mellitus over other therapeutic alternatives available.

The systemic administration of oleoylethanolamide exerts neuroprotection of the nigrostriatal system in experimental Parkinsonism.

Oleoylethanolamide (OEA) is an agonist of the peroxisome proliferator-activated receptor α (PPARα) and has been described to exhibit neuroprotective properties when administered locally in animal models of several neurological disorder models, including stroke and Parkinson's disease. However, there is little information regarding the effectiveness of systemic administration of OEA on Parkinson's disease. In the present study, OEA-mediated neuroprotection has been tested on in vivo and in vitro models of 6-hydroxydopamine (6-OH-DA)-induced degeneration. The in vivo model was based on the intrastriatal infusion of the neurotoxin 6-OH-DA, which generates Parkinsonian symptoms. Rats were treated 2 h before and after the 6-OH-DA treatment with systemic OEA (0.5, 1, and 5 mg/kg). The Parkinsonian symptoms were evaluated at 1 and 4 wk after the development of lesions. The functional status of the nigrostriatal system was studied through tyrosine-hydroxylase (TH) and hemeoxygenase-1 (HO-1, oxidation marker) immunostaining as well as by monitoring the synaptophysin content. In vitro cell cultures were also treated with OEA and 6-OH-DA. As expected, our results revealed 6-OH-DA induced neurotoxicity and behavioural deficits; however, these alterations were less severe in the animals treated with the highest dose of OEA (5 mg/kg). 6-OH-DA administration significantly reduced the striatal TH-immunoreactivity (ir) density, synaptophysin expression, and the number of nigral TH-ir neurons. Moreover, 6-OH-DA enhanced striatal HO-1 content, which was blocked by OEA (5 mg/kg). In vitro, 0.5 and 1 μM of OEA exerted significant neuroprotection on cultured nigral neurons. These effects were abolished after blocking PPARα with the selective antagonist GW6471. In conclusion, systemic OEA protects the nigrostriatal circuit from 6-OH-DA-induced neurotoxicity through a PPARα-dependent mechanism.