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Risk-sharing agreements(RSA) allow decision-makers to manage the uncertainty associated with effectiveness and costs of treatments. Our objective was to estimate the economic impact of RSA implementation on treatment of patients diagnosed with rheumatoid arthritis(RA) with certolizumab pegol(CZP) and assess the potential impact of alternative RSA.Under original RSA, treatment with CZP was reimbursed when the response was optimal (DAS28 score3.2) or satisfactory (DAS28 score ≥3.2 and reduction from baseline ≥1.2) at 12 weeks. Alternative RSA would additionally include a 50 % reimbursement for moderate responders(DAS28 score3.2 and ≤5.1, and reduction from baseline between 0.6 and 1.2). We estimated average savings per patient for hospital's pharmacy service(HPS) at 12 weeks, taking into account the pharmacological cost of CZP. Uncertainty associated with effectiveness of CZP was assessed through 1000 Monte Carlo simulations.After 12 weeks of treatment, 57.8 % (n = 52) and 22.2 %(n = 20) of patients had optimal and satisfactory responses, respectively, and average disease activity improved by 1.77 points. Average savings for HPS amounted to 876.9€ and 706.4€ per patient under original and alternative RSA, respectively. Savings in simulated cohort reached 846.2€ and 681.8€ per patient, respectively, leading to estimated net savings for HPS of 846,209€ and 681,790€, respectively.RSA implementation on patients with RA treated with CZP has generated savings and improved efficiency within HPS.

Objective To assess the economic impact of introducing biosimilars of bevacizumab for the management of cancer patients receiving systemic bevacizumab in the National Health System (SNHS) of Spain. Methods A 3-year budget impact analysis model was adapted to estimate the cost of introducing biosimilars of bevacizumab in the SNHS for the adult population who were candidates to receive treatment with bevacizumab. Values for the estimation of the population were obtained from the literature and were validated by an expert panel. In this analysis only pharmaceutical costs (euro, year 2021) obtained from official databases were considered. A sensitivity analysis was performed to examine the robustness of the model. Results The introduction of bevacizumab biosimilars would generate an annual cost saving of euro11 558 268 (-5.1%) for the first year with a penetration share of biosimilars from 30.0%, euro29 126 373 (-8.5%) for the second year with a share of 50.0% and euro52 361 778 (-13.6%) for the third year with a share of 80.0%. The total pharmaceutical costs of the scenario without biosimilars are euro227 033 352 for the first year, euro342 663 209 for the second year and euro385 013 076 for the third year. In contrast, the pharmaceutical costs of the scenario with bevacizumab biosimilars are euro215 475 084, euro313 536 836 and euro332 651 297 for years 1, 2 and 3, respectively. Conclusions The introduction of biosimilars in the Spanish Health System would generate saving costs in the pharmacological budget to boost biological drugs from the first year.

The introduction of new therapies for the treatment of multiple sclerosis (MS) is a very recent phenomenon and little is known of their mechanism of action. Moreover, the response is subject to interindividual variability and may be affected by genetic factors, such as polymorphisms in the genes implicated in the pathologic environment, pharmacodynamics, and metabolism of the disease or in the mechanism of action of the medications, influencing the effectiveness of these therapies. This review evaluates the impact of pharmacogenetics on the response to treatment with new therapies in patients diagnosed with MS. The results suggest that polymorphisms detected in the GSTP1, ITGA4, NQO1, AKT1, and GP6 genes, for treatment with natalizumab, ZMIZ1, for fingolimod and dimethyl fumarate, ADA, for cladribine, and NOX3, for dimethyl fumarate, may be used in the future as predictive markers of treatment response to new therapies in MS patients. However, there are few existing studies and their samples are small, making it difficult to generalize the role of these genes in treatment with new therapies. Studies with larger sample sizes and longer follow-up are therefore needed to confirm the results of these studies.

Resumen Introduccion La variabilidad genetica individual favorece que la capacidad de respuesta y toxicidad a los farmacos sea diferente en cada persona. En la artritis reumatoide se reportan indices de respuesta a los medicamentos etanercept, infliximab, adalimumab y metotrexato cercanos al 60%. Esta variabilidad puede explicarse por polimorfismos geneticos caracteristicos de cada paciente. Objetivo Identificar polimorfismos geneticos reportados en articulos cientificos que pueden afectar la farmacocinetica y la farmacodinamica de etanercept, infliximab, adalimumab y metotrexato, y su respuesta en pacientes con artritis reumatoide. Materiales y metodo Se realizo una busqueda sistematica en PubMed/Medline, con los terminos clave: «rheumatoid arthritis» and «pharmacogenomic» and «polymorphisms» and «metotrexato» and «infliximab» and «adalimumab» and «etanercept» obteniendo 164 articulos, 117 no duplicados y 19 articulos que cumplieron los criterios de inclusion. Resultados De los 19 articulos, 2 reportaron polimorfismos que afectan la farmacocinetica de infliximab, adalimumab, etanercept y metotrexato, y 17, la farmacodinamica. En los 19 articulos se identificaron 23 polimorfismos de relevancia clinica en poblacion europea, japonesa, jordana e india. Conclusiones Se identifican 23 polimorfismos de relevancia clinica, los cuales podrian ser el soporte para el diseno de un test de secuenciacion especifica en pacientes con artritis reumatoide, en los que se considere la utilizacion de infliximab, adalimumab, etanercept o metotrexato. La utilidad practica de este tipo de estrategia requiere ser evidencia en estudios clinicos especificos, relacionados con una prescripcion orientada por test geneticos y personalizada, y su efecto sobre la efectividad y seguridad de la farmacoterapia con estos medicamentos.

Breast cancer (BC) is the most frequent neoplasm and one of the main causes of death in women. The pharmacological treatment of BC consists of hormonal therapy , chemotherapeutic agents and targeted therapy. The response to BC therapy is highly variable in clinical practice. This variability can be explained by the presence of genetic polymorphisms in genes involved in the pharmacokinetics , pharmacodynamics or immune response of patients. The abundant evidence of associations between low-activity alleles CYP2D6*3, *4, *5, *6, *10 and *41 and poor results with tamoxifen therapy, and between DPYD gene polymorphisms rs3918290, rs55886062, rs67376798 and rs75017182 and increased risk of toxicity to fluoropyrimidine therapy, justify the existence of clinical pharmacogenetic guidelines. The NQO1 rs1800566 polymorphism is related to poorer results in BC therapy with chemotherapy agents . The polymorphism rs1695 of the GSTP1 gene has been associated with the effectiveness and toxicity of fluorouracil , cyclophosphamide and epirubicin therapy. Finally, the HLA-DQA1*02:01 allele is significantly associated with the occurrence of liver toxicity events in patients receiving lapatinib . There is moderate evidence to support the aforementioned associations and, therefore, a high probability of these being considered as future predictive genetic biomarkers of response. However, further studies are required to reinforce or clarify their clinical relevance.

Background Biological agents, such as infliximab, have transformed the outcomes of patients with immune-mediated inflammatory diseases. The advent of biosimilar treatment options such as CT-P13 promises to improve the availability of biological therapy, yet real-world switching data are currently limited. Here, we assess the effectiveness and safety of switching to CT-P13 from infliximab reference product (RP) in patients with inflammatory bowel disease. Materials and methods This was a prospective single-center observational study in patients with moderate to severe Crohn’s disease (CD) and ulcerative colitis (UC). All patients were switched from infliximab RP (Remicade) to CT-P13 treatment and followed up for up to 12 months. The efficacy endpoint was the change in clinical response assessed at 3-monthly intervals, according to the Harvey–Bradshaw score and partial Mayo score for patients with CD and UC, respectively. C-reactive protein (CRP) was also measured. Adverse events were monitored and recorded throughout the study. Results A total of 98 patients with inflammatory bowel disease (67 CD/31 UC) were included. A total of 83.6% (56/67) of patients with CD were in remission at the time of the switch and 62.7% were in remission at 12 months. The Harvey–Bradshaw score showed a significant change at 12 months (P=0.007) but no significant change was observed in median CRP at this timepoint (P=0.364). A total of 80.6% (25/31) of patients with UC were in remission at the time of the switch and 65.3% (18/28) were in remission at 12 months. No significant changes in the median partial Mayo score (P=0.058) or CRP (P=0.329) were observed at 12 months. Serious adverse events related to medication were reported in 11 (11.2%) patients. Conclusion Switching from infliximab RP to CT-P13 is efficacious and well tolerated in patients with CD or UC for up to 12 months.

Multiple Sclerosis (MS) is a progressive disease leading to increasing disability and costs. A literature review was carried out to identify MS costs and to estimate its economic burden in Spain. Areas Covered: The public electronic databases PubMed, ScienceDirect and IBECS were consulted and a manual review of communications presented at related congresses was carried out. A total of 225 references were obtained, of which 43 were finally included in the study. Expert Commentary: Three major cost groups were identified: direct healthcare costs, direct non-healthcare costs and indirect costs. There is a direct relationship between disease progression and increased costs, mainly direct non-healthcare costs (greater need for informal care) and indirect costs (greater loss of productivity). The total cost associated with MS in Spain is €1,395 million per year, and that the mean annual cost per patient is €30,050. Beyond costs, a large impact on the quality of life of patients, with an annual loss of up to 13,000 quality-adjusted life years was also estimated. MS has a large economic impact on Spanish society and a significant impact on the quality of life of patients.

Oral syringes are the preferred method for delivering paediatric enteral drugs; however, little is known about factors affecting accuracy, particularly at volumes5 mL. We investigated volumetric accuracy for enteral syringes, using commercially available liquid drug formulations with various physicochemical properties at clinically relevant volumes.In vitro experiment.Ten drugs were tested using two syringe brands (Baxa, Medicina) across a range of formulation volumes (0.05-5 mL) and syringe sizes (1-5 mL). Syringe weights (empty and filled) were converted into volume, using known formulation densities. Ten replications were performed for each drug/syringe/volume combination.Delivered volume accuracy was expressed as a percentage of intended volume, with the desired range being within ±10%.Baxa demonstrated a slight positive bias (excess average volumes delivered) at the smallest volumes for each syringe size, while Medicina had poorer precision (greater variability, analysis of variance-interactions all p0.005). From these results, we identified the limit for volume accuracy for each syringe size and brand. Of note, the 1 mL syringe for both brands was inaccurate for delivering volumes ≤0.1 mL. The physicochemical properties of pH (range 2.82-7.45), surface tension (30.2-86.7 mN/m) and viscosity (2-299 mPaS) did not influence error in a discernible pattern.Dosing was inaccurate when small volumes were used across all syringe sizes and brands. These reflect volumes used in clinical practice. Administration error could potentially be reduced by (1) clinicians using syringes appropriate to dosing volumes and (2) manufacturers revising formulation concentrations for drugs.

A regular consumption of virgin olive oil (VOO) is associated with a reduced risk of cardiovascular disease. We aimed to assess whether the raw intake of an optimized VOO (OVOO, 490 ppm of phenolic compounds and 86 ppm of triterpenes), and a functional olive oil (FOO, 487 ppm of phenolic compounds and enriched with 389 ppm of triterpenes) supplementation (30 mL per day) during three weeks would provide additional health benefits to those produced by a standard VOO (124 ppm of phenolic compounds and 86 ppm of triterpenes) on oxidative and inflammatory biomarkers. Fifty-one healthy adults participated in a randomized, crossover, and controlled study. Urinary 8-hidroxy-2′-deoxyguanosine, plasma interleukin-8 (IL-8), and tumor necrosis factor α (TNF- α) concentrations were lower after the intervention with the FOO than after the OVOO (p = 0.033, p = 0.011 and p = 0.020, respectively). In addition, IL-8 was lower after the intervention with FOO than after VOO intervention (p = 0.002). This study provides a first level of evidence on the in vivo health benefits of olive oil triterpenes (oleanolic and maslinic acids) in healthy humans, decreasing DNA oxidation and plasma inflammatory biomarkers. The trial was registered in ClinicalTrials.gov ID: NCT02520739., The “NUTRAOLEUM Study” has been supported by the grant ITC-20131031 from the I+D FEDER-INTERCONNECTA (CDTI) and Junta de Andalucía, Spain. We thank ACER CAMPESTRES S.L., SAN FRANCISCO DE ASIS Coop. And., and AGROINSUR S.L., for the funding provided. We appreciate the support received from the workers of the clinical trials unit of the “Virgen de las Nieves” and “San Cecilio” hospitals by finding subjects for the study and for their involvement in the intervention; we thank Laura Campaña Martín, Maria Victoria Martín Laguna and Mª Cruz Rico Prados who carried out technical work, sample preparation and biomarker analyses, and Llenalia Garcia Fernández, who supervised the statistical analysis, We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI)

Background: nutritional support (NS) is a core element in the treatment of underweight patients with anorexia nervosa (AN). Objective: to analyze the adherence of NS prescriptions to clinical practice guidelines (CPGs) for AN patients and to compare the effectiveness, safety, and cost of NS according to adherence. Methods: this retrospective observational study included AN patients admitted to an Eating Disorders Unit between January 2006 and December 2009 and followed until December 2014. NS prescriptions were compared with guidelines published by the American Psychiatric Association (APA), the National Institute for Clinical Excellence (NICE), and the Spanish Ministry of Health and Consumption (SMHC). Adherence was defined as percentage of hospitalizations that followed all recommendations. Results: adherence to APA and NICE/SMHC was observed in 10.2% and 73.4%, respectively, of the total of 177 hospitalizations. Body weight and body mass index were higher at admission in the NICE/SMHC adherence versus non-adherence group (p0.001). Weight gain rate during hospitalization was higher (p = 0.009) in "APA adherence" (135.5 g/day) versus "non-adherence" (92.1 g/day) group. Hospital stay was significantly shorter (p = 0.025) in "NICE/SMHC adherence" (39.5 days) versus "non-adherence" group (50.0 days). NICE/SMHC adherence was associated with lower costs (p = 0.006). Conclusions: NS prescriptions for anorexic patients more frequently followed NICE/SMHC than APA recommendations. Over the short-term, APA adherence was associated with improved weight gain. Patients adhering to NICE/SMHC recommendations had shorter hospital stay and reduced costs, likely due to their more favorable nutritional status at admission.Introducción: el soporte nutricional (SN) es un elemento clave en el tratamiento de la anorexia nerviosa (AN). Objetivo: analizar la adecuación de las prescripciones de SN en pacientes con AN a las guías de práctica clínica (GPC) y comparar la efectividad, seguridad y coste según la adecuación. Métodos: estudio observacional retrospectivo en pacientes con AN ingresados en una Unidad de Trastornos de Conducta Alimentaria entre enero de 2006 y diciembre de 2009. Se hizo seguimiento hasta diciembre de 2014. Se compararon las prescripciones de SN con las GPC publicadas por la Asociación Americana de Psiquiatría (APA), el Instituto Nacional de Excelencia Clínica (NICE) y el Ministerio Español de Sanidad y Consumo (MSC). Se definió adecuación como porcentaje de ingresos que cumplieron todas las recomendaciones. Resultados: el grado de adecuación a APA y NICE/MSC fue del 10,2% y 73,4%, respectivamente. El peso corporal y el índice de masa corporal al ingreso fueron mayores en el grupo “sí-adecuación” al NICE/MSC versus “no-adecuación” (p0,001). La tasa de ganancia ponderal fue superior (p = 0,009) en el grupo “sí-adecuación” a APA (135.5 g/día) versus “no-adecuación” (92,1 g/día). La estancia hospitalaria fue menor (p = 0,025) en “sí-adecuación” al NICE/MSC (39,5 días) versus “no-adecuación” (50,0 días). La adecuación al NICE/MSC fue asociada con menores costes (p = 0,006). Conclusiones: las prescripciones de SN se ajustaron en mayor grado al NICE/MSC que a la APA. La adecuación a APA parece relacionarse con mayor tasa de ganancia ponderal. Los pacientes que se adecuaron al NICE/MSC presentaron menores estancias hospitalarias y costes, probablemente relacionado con su estado nutricional más favorable al ingreso.

Background Community-acquired pneumonia (CAP) is a frequent cause of morbidity, mortality and hospital admission worldwide. An adequate choice of empirical antibiotic treatment and appropriate severity assessment of the disease are key aspects in the management of CAP. Objective To audit the adherence to standards of care, such as empirical prescribing of antibiotics, and evaluate the current multidisciplinary approach to the management of CAP. Method Records of patients with CAP were identified and examined for CURB65 score documentation, discussion notes with microbiology and prescribed antibiotic treatments. Results Out of the 62 patients identified, 32 had a CURB65 score documented in their medical notes and 59 had documented chest X-ray findings. 85.5% of cases were compliant with antibiotic prescribing guidelines. Conclusion The multidisciplinary approach has considerably improved compliance with most of the standards, especially adherence to empirical antibiotic guidelines, and ultimately the standard of care for patients with CAP.

Background The National Patient Safety Agency reported over 20 000 safety incidents over a 3-year period, including 68 severe harms and 27 deaths. Dose delays and omissions persistently contributed to more than 50% of the reported incidents. Methods A pilot was designed and data were collected before and after to measure how these ward-based technician roles affected the reporting of omitted or delayed doses, time efficiency, cost implications and the general productivity of the ward. Results Three months after the start of the pilot, omitted doses were reduced from 14% to 5% and no incidents of harm had been reported. The ‘perfect medication ward round’ with no interruptions lasted 23 min compared with the longest medication ward round which lasted 116 min and was interrupted 11 times. Conclusions The pilot shows that the introduction of pharmacy technicians results in fewer omitted doses and also addresses persistent staffing issues by ensuring better use of nursing time.

RESUMEN Introducción: La variabilidad genética individual favorece que la capacidad de respuesta y toxicidad a los fármacos sea diferente en cada persona. En la artritis reumatoide se reportan índices de respuesta a los medicamentos etanercept, infliximab, adalimumab y metotrexato cercanos al 60%. Esta variabilidad puede explicarse por polimorfismos genéticos característicos de cada paciente. Objetivo: Identificar polimorfismos genéticos reportados en artículos científicos que pueden afectar la farmacocinética y la farmacodinámica de etanercept, infliximab, adalimumab y metotrexato, y su respuesta en pacientes con artritis reumatoide. Materiales y método: Se realizó una búsqueda sistemática en PubMed/Medline, con los términos clave: «rheumatoid arthritis» and «pharmacogenomic» and «polymorphisms» and «metotrexato» and «infliximab» and «adalimumab» and «etanercept» obteniendo 164 artículos, 117 no duplicados y 19 artículos que cumplieron los criterios de inclusión. Resultados: De los 19 artículos, 2 reportaron polimorfismos que afectan la farmacocinética de infliximab, adalimumab, etanercept y metotrexato, y 17, la farmacodinámica. En los 19 artículos se identificaron 23 polimorfismos de relevancia clínica en población europea, japonesa, jordana e india. Conclusiones: Se identifican 23 polimorfismos de relevancia clínica, los cuales podrían ser el soporte para el diseño de un test de secuenciación específica en pacientes con artritis reumatoide, en los que se considere la utilización de infliximab, adalimumab, etanercept o metotrexato. La utilidad práctica de este tipo de estrategia requiere ser evidencia en estudios clínicos específicos, relacionados con una prescripción orientada por test genéticos y personalizada, y su efecto sobre la efectividad y seguridad de la farmacoterapia con estos medicamentos. ABSTRACT Introduction: Individual genetic variability favors the capacity of response and toxicity to the drugs is different in each person. Rheumatoid arthritis reported rates of response to the drugs etanercept, infliximab, adalimumab and methotrexate is close to 60%. This variability can be explained by genetic polymorphisms characteristic of each patient. Objective: To identify genetic polymorphisms reported in scientific articles that may affect the pharmacokinetics and pharmacodynamics of etanercept, infliximab, adalimumab, and methotrexate, and their response in patients with rheumatoid arthritis. Materials and method: A systematic search was performed in PubMed and Medline, with the key terms: "rheumatoid arthritis" and "pharmacogenomic" and "polymorphisms" and "methotrexate" and "infliximab" and "adalimumab" and "etanercept", obtaining 164 articles, 117 non-duplicates, and 19 articles that met the inclusion criteria. Results: Of the 19 articles, 2 reported polymorphisms affecting the pharmacokinetics of infliximab, adalimumab, etanercept, methotrexate, and 17, pharmacodynamics. In the 19 articles, 23 polymorphisms of clinical relevance were identified in European, Japanese, Jordanian, and Indian populations. Conclusions: A total of 23 polymorphisms with clinical relevance were identified, which could be the basis for the design of a specific test sequencing in rheumatoid arthritis patients being considered for treatment with infliximab, adalimumab, etanercept, or methotrexate. The practical usefulness of this strategy requires evidence in specific clinical studies, associated with a targeted and personalized genetic test, and its effect on the effectiveness and safety of drug therapy with these drugs prescription.

Sorafenib is an oral multikinase inhibitor with antiangiogenic and antiproliferative properties, and is used as the first-line treatment for patients with advanced hepatocellular carcinoma (HCC). Previous studies have identified an improvement in overall survival and progression-free survival in patients with a manageable toxicity profile. α-fetoprotein (AFP) has been revealed to be of great diagnostic and predictive value for tumour staging in multiple studies; however, its role as a predictive factor of response to treatment with sorafenib is not entirely clear. The present study aimed to determine the effectiveness of sorafenib and investigate the value of AFP as a predictive factor of early response to sorafenib in patients with HCC. Effectiveness was analysed based on median overall survival (mOS) time, while to analyse the possible predictive value of AFP, patients were classified into two groups: Non-responders (≤20% AFP reduction) and responders (>20% AFP reduction) at 6-8 weeks of treatment when compared with basal AFP level. For assessment of toxicity, any adverse effects were recorded. A total of 167 patients were included, who collectively exhibited a mOS time of 11 months with a median treatment duration of 5 months. The mOS time was significantly higher for patients with better hepatic function (12 months in cases of Child-Pugh score A vs. 8 months in cases of Child-Pugh score B; P=0.03) and with basal AFP values ≤200 ng/ml (14 months vs. 8 months in patients with AFP levels >200 ng/ml; P=0.01). A >20% reduction of AFP at 6-8 weeks was determined to be a positive predictive factor upon multivariate analysis (P=0.002), obtaining, for the responder patients, an mOS of 18 months compared with 10 months (P=0.004) for the non-responders. The main adverse reactions were hand-foot syndrome (35/167; 21%), diarrhoea (39/167; 23.4%), anorexia (29/167; 17.4%) and arterial hypertension (30/167; 18%). In conclusion, a >20% drop in AFP at 6-8 weeks may be useful as a predictive factor of response to sorafenib, as indicated by its association with longer survival times in patients with advanced HCC following treatment with sorafenib in the present study.

BACKGROUND Infliximab original has changed the natural history of inflammatory bowel diseases (IBD) over the past two decades. However, the recent expiration of its patent has allowed the entry of the first Infliximab biosimilar into the European and Spanish markets. Currently switching drugs data in IBD are limited. AIM To compare the efficacy of infliximab biosimilar, CT-P13, against infliximab original, analyzing the loss of response of both at the 12 mo follow-up in patients with IBD. METHODS An observational study of two cohorts has been conducted. One retrospective cohort that included patients with IBD treated with Infliximab original, and a prospective cohort of patients who were switching from infliximab original to infliximab biosimilar (CT-P13). We had analyzed the overall efficacy and loss of efficacy in patients in remission at the end of one year after treatment with the original drug compared to the results of the year of treatment with the biosimilar. RESULTS 98 patients (CD 67, CU 31) were included in both cohorts. The overall efficacy for infliximab original per year of treatment was 71% vs 68.2% for infliximab biosimilar (P = 0.80). The loss of overall efficacy at 12 mo for infliximab original was 6.6% vs 14.5% for infliximab biosimilar (P = 0.806). The loss of efficacy in patients who were in basal remission was 16.3% for infliximab original vs 27.1% for infliximab biosimilar. Adverse events were 9.2% for infliximab original vs 11.2% for infliximab biosimilar. CONCLUSION The overall efficacy and loss of treatment response with infliximab biosimilar (CT-P13) is similar to that observed with infliximab original in patients who were switching at the 12 mo follow-up. There is no difference in the rate of adverse events.

17 Páginas; 3 Figuras; 5 Tablas, The aim of this study was to evaluate the effect of virgin olive oils (VOOs) enriched with phenolic compounds and triterpenes on metabolic syndrome and endothelial function biomarkers in healthy adults. The trial was a three-week randomized, crossover, controlled, double-blind, intervention study involving 58 subjects supplemented with a daily dose (30 mL) of three oils: (1) a VOO (124 ppm of phenolic compounds and 86 ppm of triterpenes); (2) an optimized VOO (OVOO) (490 ppm of phenolic compounds and 86 ppm of triterpenes); and (3) a functional olive oil (FOO) high in phenolic compounds (487 ppm) and enriched with triterpenes (389 ppm). Metabolic syndrome and endothelial function biomarkers were determined in vivo and ex vivo. Plasma high density lipoprotein cholesterol (HDLc) increased after the OVOO intake. Plasma endothelin-1 levels decreased after the intake of the three olive oils, and in blood cell cultures challenged. Daily intake of VOO enriched in phenolic compounds improved plasma HDLc, although no differences were found at the end of the three interventions, while VOO with at least 124 ppm of phenolic compounds, regardless of the triterpenes content improved the systemic endothelin-1 levels in vivo and ex vivo. No effect of triterpenes was observed after three weeks of interventions. Results need to be confirmed in subjects with metabolic syndrome and impaired endothelial function (Clinical Trials number NCT02520739)., The “NUTRAOLEUM Study” has been supported by the grant ITC-20131031 from the I+D FEDER-INTERCONNECTA (CDTI) and Junta de Andalucía, Spain”. We thank ACER CAMPESTRES S.L., SAN FRANCISCO DE ASIS Coop and AGROINSUR S.L., for the funding provided. The authors thank Pilar Jiménez, Alberto Guarnido, María Molina and Elizabeth García for administering the questionnaires to the subjects; Isabel Mérida, Isabel Hinojosa, Agustín Martín García, and María Luz Abarca for collecting the biological samples; and Victoria Martín Laguna and Laura Campaña Martín for aliquoting the samples. The authors also thank María Cruz Rico Prados for sample analysis and Llenalia M. García Fernández for her contributions to the statistical analysis.

Pharmacists play a crucial role in the evaluation of the effectiveness of healthcare systems, as they are the only professionals who can measure mean health outcomes against the cost of medication use.1 Today, hospital pharmacists act as expert advisors in decision-making on the most cost-effective alternatives for medicines agencies or, locally, in hospital pharmacy commissions. Hospital pharmacists have also evaluated their own service. From the creation of pharmacy services until the last decade, various cost-effectiveness analyses have been conducted of pharmacy services.2–4 These analyses have aimed primarily to use economic impact as one of the main arguments in favour of the creation of pharmacy services within hospitals. It can be concluded that, in general, the pharmacy model has been demonstrated to be also profitable, and it is implemented all over the world. However, the evaluation of cost-effectiveness of hospital pharmacy services is based on interventions that included a full economic analysis but only performed in single centres or in isolated interventions in few kinds of drugs. But that profitability does not necessarily …

To detect the frequency of negative outcomes associated with medication in patients with permanent atrial fibrillation (AF) who are attended in a hospital emergency department, and to assess type and severity of such outcomes related to AF medications as well as the rate of preventable negative outcomes.Descriptive, observational cross-sectional study in patients with permanent AF who were attended in the emergency department of a tertiary care hospital during a 3-month period. A pharmacist interviewed the patients to record demographic characteristics, health problems, degree of functional impairment, and current drug treatments. An emergency physician and a pharmacist reviewed the patients' questionnaires and medical histories and evaluated them using the Dader method of pharmacotherapeutic follow-up.Of the 210 patients assessed, 198 entered the final analysis. They had a mean (SD) age of 80.5 (7.3) years, and 114 (57.5%) were women. One handred and thirty-four (67.7%) patients had medication-related negative outcomes; 61 (45.5%) of the outcomes were related to treatment for permanent AF. Twenty-four of these 61 patients (39.3%) had problems affecting safety; 36 (59%) of the problems were caused by drugs to control heart rate. Of the 73 patients with negative outcomes unrelated to AF medication, 34 (46.6%) were related to necessary medications and 38 (52.1%) were taking antibiotics. The frequencies of avoidable negative outcomes were significantly different between the group of patients with problems related to drug therapy for AF (where 55.7% were due to medications considered unnecessary) and those with problems unrelated to AF medications (where 78.1% were from avoidable medications) (P=.010). However, the level of seriousness was similar.Nearly two-thirds of patients with permanent AF who come to the emergency department have a medication- related negative outcome that may or may not be related to AF treatment. Problems from drugs taken for reasons other than AF could more easily be avoided.Detectar la frecuencia de resultados negativos asociados a la medicación (RNM) en los pacientes con fibrilación auricular permanente (FAP) atendidos en un servicio de urgencias hospitalario (SUH), y evaluar su tipología, evitabilidad y gravedad en función de su relación con la terapia farmacológica para la fibrilación auricular (FA).Estudio observacional descriptivo de una serie de casos con análisis transversal que incluyó a los pacientes atendidos con FAP en un servicio de urgencias (SU) de un hospital de tercer nivel durante 3 meses. Un farmacéutico entrevistó a los pacientes recogiendo datos demográficos, problemas de salud, grado de dependencia y terapia farmacológica. Un grupo evaluador, formado por un urgenciólogo y un farmacéutico, revisaron los cuestionarios y las historias clínicas para la evaluación de los RNM según el método Dáder.Del total de 210 pacientes evaluados se incluyeron finalmente 198 pacientes con una edad media de 80,5 (DE 7,3) años, de los cuales 114 (57,5%) fueron mujeres. Ciento treinta y cuatro (67,7%) pacientes sufrieron un RNM, de los cuales 61 (45,5%) estaban relacionadas con el tratamiento de la FA (RNM-RTFA). De los 61 pacientes con RNM-RTFA, 24 (39,3%) fueron RNM de seguridad y 36 (59%) estaban causados por los fármacos para el control de la frecuencia. De los 73 pacientes con RNM no relacionadas con el tratamiento de la FA (RNM-NRTFA), 34 (46,6%) fueron RNM de necesidad y 38 (52,1%) eran por antibióticos. Entre los dos grupos, hubo diferencias estadísticamente significativas en cuanto a la evitabilidad (RNM-RTFA 55,7% vs RNM-NRTFA 78,1%; p = 0,010), pero no para la gravedad (p = 0,265).Casi dos tercios de los pacientes con FAP que acuden a un SUH sufren un RNM relacionado o no con la medicación específica para la FA, siendo más evitables los RNM del grupo de fármacos no relacionados con el tratamiento de esta enfermedad.

The purpose of this study was to analyze the adherence of psychopharmacological prescriptions to clinical practice guidelines (CPGs) for patients with eating behavior disorders (EDs) and to compare the effectiveness, safety, and cost of treatment according to adherence. This retrospective observational study included ED patients admitted to the eating disorders unit (EDU) of Ciudad Real Hospital (Spain) between January 2006 and December 2009 and followed until December 2014. Psychopharmaceuticals prescribed during EDU stay(s) were compared with guidelines published by American Psychiatric Association (APA), National Institute for Clinical Excellence (NICE), and Spanish Ministry of Health and Consumption (SMHC). Adherence was considered as the percentage of patients whose prescription followed all recommendations. The study included 113 ED patients. Adherence to APA and NICE/SMHC was 30.1% and 45.1%, respectively. Weekly weight gain during hospital stay was higher (p = 0.037) in the APA “adherence” (807.6 g) versus “non-adherence” (544.4 g) group. An association was found between CPG adherence and higher 5-year full recovery rate (p

Olive oil is rich in several minor components like maslinic (MA) and oleanolic (OA) acids which have cardioprotective, antitumor, and anti-inflammatory properties. In order to assess the health benefits in humans provided by the olive oil triterpenes (MA and OA), suitable analytical methods able to quantify the low concentrations expected in human fluids are required. In this study, the LC-MS/MS quantification of both OA and MA in plasma and urine has been evaluated. The plasmatic method is based on the direct determination of the analytes. The urinary detection requires more sensitivity which was reached by derivatization with 2-picolylamine. Additionally, the urinary species present after MA and OA ingestion were evaluated by the direct detection of several phase II metabolites previously synthesized. Our results showed that OA is metabolized as both sulfate and glucuronide conjugates whereas MA is mainly excreted as glucuronide. Based on this information, the method for the urinary detection of MA and OA involved an enzymatic hydrolysis. Both plasmatic and urinary methods were validated with suitable precision and accuracy at all tested levels. Required sensitivity was achieved in both matrices. Up to our knowledge, this is the first method able to quantify the low concentration levels of triterpenes present in urine. Samples from two healthy volunteers who received virgin olive oils with different triterpenes content were analyzed. Some preliminary clues on the metabolic disposition of OA and MA after olive oil intake are provided.

JOURNAL ARTICLE; The emergence of novel drugs corresponds with the determination of the effectiveness of the current treatments used in clinical practice. A retrospective observational study was conducted to evaluate the effectiveness of first-line treatments and to test the influence of the prognostic factors established using the Memorial Sloan-Kettering Cancer Center (MSKCC) and the analysis of Mekhail's study for two or more metastatic sites. The primary endpoints were median progression-free survival (mPFS) and median overall survival (mOS) times. A total of 65 patients were enrolled and the mPFS and mOS of the patients treated with sunitinib (n=51) were 9.0 and 20.1 months, respectively, and for the patients treated with temsirolimus (n=14) these were 3.0 and 6.2 months, respectively. In the poor-prognosis (PP) group, a difference of 1.2 months (P=0.049) was found in mPFS depending on the first-line treatment. A difference of 4.1 months (P=0.023) was also found in mPFS when classified by histology (clear verses non-clear cell) in the sunitinib-treatment group. When stratified by the prognostic group, differences of >7 months (P

Objectives To evaluate the quality of life (QOL) of a cohort of women undergoing assisted reproduction techniques (ART), to compare two QOL questionnaires [Short Form 36 (SF36) and FertiQoL], and to identify the predictive factors related to QOL. Study design Women who received infertility medication from a hospital pharmacist during a one-year period were included in this study. Two standardized validated questionnaires – FertiQoL and SF36 – were used. Multivariate analyses were used to assess predictive factors for QOL. Results Sixty-one women participated in this study. Median QOL scores ranged from 58 to 100. Comparisons between the two questionnaires revealed lower QOL scores when using FertiQoL. Most correlations between the questionnaires were positive, and significant for the majority of SF36 mental dimensions. The major predictors of QOL were: accompanied to the pharmacist's visit by partner, nationality, ART (in vitro fertilization or artificial insemination), employment status (employed or unemployed), tobacco consumption, age, number of cycles, infertility factor and treatment results (pregnancy, no pregnancy or treatment cancellation). Conclusions FertiQoL examines dimensions such as partner and social relationships. As such, it is recommended that FertiQoL should be used together with a short version of SF36 to investigate QOL among patients undergoing ART.

JOURNAL ARTICLE; A retrospective cohort study was conducted to analyse the effectiveness of bevacizumab and irinotecan (BVZ/CPT-11) as a second-line treatment in patients with primary glioblastoma multiforme (GBM) in comparison with a control group that were not administered BVZ/CPT-11 at the first recurrence. The difference in overall survival (OS) between the two groups was used as a predictor of effectiveness. OS was calculated according to prognostic factors and gender. A total of 28 and 32 patients were enrolled in the BVZ/CPT-11 cohort and control group, respectively. The median OS was 17.94 months (95% CI, 14.91-20.96) in the BVZ/CPT-11 treatment cohort and 10.97 months (95% CI, 7.65-14.30) in the control cohort. The results obtained on the effectiveness of BVZ/CPT-11 treatment in patients with primary GBM are consistent with data from previous studies. No significant differences were identified in OS based on prognostic factors; therefore, the latter cannot be used to select patients who would incur the greatest benefits from BVZ/CPT-11 treatment. Yes

Objective The aim of this study was to quantify the level of knowledge of patients treated with fertility drugs before and after information was provided by a hospital pharmacist, the acceptability of this counselling, and patient treatment adherence. Materials and methods Infertile couples undergoing assisted reproduction techniques lasting 12 months were followed up through review of the patient9s medical notes, a personal patient interview and a structured questionnaire. Consecutive couples were enrolled. Clinical patient data were collected from the patient9s medical notes and patient medication knowledge was assessed by personal interview before and after pharmacy counselling. Acceptability by patients was evaluated using a questionnaire and adherence to treatment using hospital dispensing information. Results 61 patients were included and 22 (36.06%) completed the acceptability questionnaire. The global satisfaction rate was 92.4% (4.62 points out of 5). There was 100% patient adherence to treatment. The percentage of medication knowledge was 60.9% before pharmacist counselling and 90% (increase of 29.2%) after counselling. Conclusions This study provides reassurance of the high adherence to treatment of these patients. Patients are receptive to counselling and satisfied with pharmaceutical care. Information received and ease of staff contact were rated highest and pharmacy opening hours were rated lowest. The difference in knowledge before and after pharmaceutical counselling implies such care is beneficial.

A longitudinal, observational prospective panel cohort study of 61 patients lasting one year was undertaken. Explanatory variables included sociodemographic factors along with factors related to the underlying pathology as well as the protocol used and the type of treatment received. These variables were analyzed both individually and in combination to account for confounding effects and model interactions. A generalized estimating equation (GEE) model was constructed for each adverse effect. Associations were calculated as odds ratios (OR). Confounding variables related to drug tolerability were identified. Follitropin-alpha and cetrorelix exhibited the poorest safety profile. With respect to local adverse drug reactions (ADEs), the results obtained in our study point to statistically significant tolerability improvements for menotropin when administered in insemination. For gastrointestinal ADEs, ganirelix was the drug that showed the highest tolerability in in vitro treatments whereas follitropin-alpha showed the lowest tolerability in insemination treatments. Diverse factors related to assisted reproduction techniques (ART) influence the incidence of adverse effects. Each drug has a different safety profile with possible interactions depending on the type of assisted reproduction therapy used.

Taxanes offer clear benefits in adjuvant chemotherapy for early breast cancer. This review examines evidence to date on the clinical effectiveness and cost-effectiveness of their use in the adjuvant treatment of women with early breast cancer, based on three meta-analyses, one systematic review, five clinical practice guidelines and 16 randomized clinical trials. Against the background of a major increase in the use of docetaxel rather than paclitaxel in our setting over the past few years, implying a major increase in costs, we examined whether this higher use of docetaxel is supported by the available evidence. In this wide study, we found no evidence that regimens containing docetaxel yield greater benefits than those including paclitaxel. From an effectiveness standpoint, the change from paclitaxel to docetaxel in our setting is not justified.

Osteoporosis is one of the most common skeletal chronic conditions in developed countries, hip fracture being one of its major healthcare outcomes. There is considerable variation in the implementation of current pharmacological treatment and prevention, despite consistent recommendations and guidelines. Many studies have reported conflicting findings of genetic associations with bone density and turnover that might predict fracture risk. Moreover, it is not clear whether genetic differences exist in relation to the morbidity and efficiency of the pharmacotherapy treatments. Clinical response, including beneficial and adverse events associated with osteoporosis treatments, is highly variable among individuals. In this context, the present article intends to summarize putative candidate genes and genome-wide association studies that have been related with BMD and fracture risk, and to draw the attention to the need for pharmacogenetic methodology that could be applicable in clinical translational research after an adequate validation process. This article mainly compiles analysis of important polymorphisms in osteoporosis documented previously, and it describes the simple molecular biology tools for routine genotype acquisition. Validation of methods for the easy, fast and accessible identification of SNPs is necessary for evolving pharmacogenetic diagnostic tools in order to contribute to the discovery of clinically relevant genetic variation with an impact on osteoporosis and its personalized treatment.

Objetivos: Evaluar el impacto cardiovascular asociado al consumo de antiinflamatorios no esteroideos en un Área de Salud, estimando la asociación entre la prescripción previa de un antiinflamatorio no esteroideo al episodio de síndrome coronario agudo. Material y Métodos: Se realiza un estudio retrospectivo observacional de casos cruzados de 5 años de duración, del 1 de Enero de 2008 hasta el 31 de diciembre de 2012. Los pacientes en primer lugar fueron casos y controles (n=1.317) que tuvieron eventos cardiovasculares y fueron al servicio de Urgencias del Hospital por dicho motivo.Área de Salud de Alcázar de San Juan. Medida principal: Asociación del riesgo de sufrir un síndrome coronario agudo mediante el Odds Ratio con el consumo de antiinflamatorios no esteroideos Resultados: La asociación entre el síndrome coronario agudo y el consumo de Antiinflamatorios fue positiva y significativa, (OR 1,42; IC95% 1,06-1,9). Esta asociación fue de mayor magnitud en pacientes con menor comorbilidad, Charlson ≤ 1 (OR 1,66; IC95% 1,15 – 2,40) frente a los de mayor comorbilidad, Charlson > 1 (OR 1,07; IC95% 0,65 – 1,76). Esta modificación de efecto se debió en parte al consumo concomitante de fármacos que previenen contra patologías cardiovasculares como los antiagregantes, anticoagulantes y estatinas. Conclusiones: El consumo de antiinflamatorios no esteroideos se ha asociado a un mayor riesgo de síndrome coronario agudo, por lo que es necesario realizar un seguimiento a los pacientes que consuman estos fármacos, no debiéndose tomar durante tiempos prolongados ni a dosis altas., Aims: Evaluate cardiovascular impact related to the use of non steroidal anti-inflammatory drugs in a Health Area, by estimating the connection between the previous medical prescription of non steroidal anti-inflammatory medicines and acute coronary syndrome. Material and Methods: A retrospective observational study of clinical casecrosover during 5 years is done, from 1st of January 2008 to 31st of December 2012. In first place patients were cases and controls (n=1.317) who suffered cardiovascular accidents and went to Emergency Room. Setting: Alcazar de San Juan Health Care Area. Main measurements: Association of the risk of acute coronary syndrome by Odds Ratio with consumption of non anti-inflammatory drug. Results: The connection between acute coronary syndrome and the use of anti-inflammatory drugs was positive and significant (OR 1.42; IC95% 1.06-1.9), which means the probability of suffering a cardiovascular accident increases to 42% in patients taking non steroidal anti-inflammatory drugs. The connection between the prescription of anti-inflammatory drugs and acute coronary syndrome reached a bigger magnitude in patients with less comorbidity, Charlson ≤ 1 (OR 1.66; IC95% 1.15 – 2.40) as opposite to those with more comorbidity, Charlson > 1 (OR 1.07; IC95% 0.65 – 1.76). This change of effect was due, in part, to the concomitant use of medicines which prevent cardiovascular diseases, such as antiaggregant, anticoagulant and statins drugs. Conclusions: The use of non steroidal anti-inflammatory drugs has been connected to a higher risk of cardiovascular accidents; therefore it is necessary to realize follow-up patients who consume these drugs. These drugs must not be consumed for a long time or at high doses.

Objectives The aim of the present work was to establish a specialised pharmaceutical care programme for patients with multiple sclerosis in order to analyse its effects on patient satisfaction, the detection of drug-related problems, and the identification and resolution of negative outcomes associated with medication. Methods This was a prospective, longitudinal study with a pre/post-exposure design regarding the pharmaceutical care programme implemented: in bimonthly visits the pharmacist identified, detected and resolved drug-related problems and negative outcomes, and also provided information about the treatment. All patients with multiple sclerosis treated with immunomodulatory drugs from 1 June to 31 December 2011 were included in the study. A Likert scale questionnaire was used before and 6 months after the implementation to assess its impact on perceived patient satisfaction. Results In all, 32 patients (20 women and 12 men), with an age of 39.7±8.3 years were included. A total of 26 were receiving treatment with interferon β and 6 with glatiramer acetate. All items assessing the pharmacist9s skills and interest in the patient along with those assessing the information received by the patient showed significant improvement (p Conclusions The implementation of a specialised pharmaceutical care programme led to a significant improvement in perceived patient satisfaction. It has also allowed for better detection of drug-related problems and identification and resolution of negative outcomes associated with medication.

e18014 Background: With the increasing use of oral anticancer treatments understanding adherence patterns and patient’s information about therapy has become critical. Enzalutamide (ENZ) and Abiraterone acetate (AA) are orally administered drugs approved for the treatment of mCRPC widely prescribed; however, scarce information is available about treatment compliance and patient’s information about these compounds. This study aims to evaluate the adherence to AA and ENZ and the patient’s drug knowledge in mCRPC patients. Methods: A 20-question survey is being delivered to patients with mCRPC receiving either AA or ENZ in 8 centers across Spain. Questions cover items such as demographics, drug information, adherence and perceived benefits among other topics. Surveying is still ongoing. Results: Fifty patients have completed the survey at this time. Mean age is 72 years (range 58-87), educational level is basic in 56 %. Median duration of treatment was 9,5 months. Adherence reported is very high with 84% of the patients taking 100% of prescribed doses and 100% more than 75%. Treatment compliance does not seem to decrease over time despite only 42% of the patients reported the use of devices to secure adherence. A high compliance correlated with better symptom control. Nonetheless, many areas of improvement have been also identified. About a quarter of the patients (26%) ignored the name of the drug they were receiving and 24% whether or not they were in a clinical trial. Almost all patients were not aware of the planned duration of treatment and 70 % recognized that they did not know the consequences of a bad adherence. Eleven patients (22%) were taking AA with food outside of a clinical trial and three patients (6%) reported inadequate dosage (i.e q 12h). Conclusions: While in other diseases adherence to oral therapies has been identified as a potential limiting factor with impact in efficacy, in our series of mCRPC treatment compliance was high and maintained overtime. Yet, serious patient education pitfalls were identified. Data collection is ongoing and further analysis will be presented.

Background Transarterial chemoembolization using microspheres is a new treatment option for patients with hepatocellular carcinoma. Objective To assess the effectiveness of this technique, in terms of tumor response and overall survival rates, and to assess the procedure’s safety. Setting A General University Hospital in Spain. Methods Single-center retrospective observational study. The cohort included all patients treated between October 2006 and April 2010. Effectiveness was determined by the tumor response rate (using modified RECIST and EASL criteria) and overall survival. Safety was assessed according to the Common Terminology Criteria for Adverse Events. Main outcome measure Tumor response rate, overall survival and safety of transarterial chemoembolization in patients with hepatocelular carcinoma. Results 53 patients were treated (81.1 % men, median age 65). Baseline characteristics 98.1 % had cirrhosis, 75.5 % Child-Pugh Class A, 71.7 % Okuda I, and 94.3 % were ECOG 0. 43.4 % were waiting for a liver transplant and 56.6 % were given the treatment as a palliative measure. Eighty-one procedures were carried out, with a median of 1 per patient [1–5]. Four weeks after treatment, the objective response rate was 87.5 % and the complete response rate was 62.5 %. Median survival was 735 days (CI 95 %: 351.9–1118.1). The 1, 2 and 3-year overall survival rates were 65.4, 50.9 and 42.5 %, respectively. 71.7 % of patients experienced post-embolization syndrome, with grade 1 abdominal pain as the most frequent symptom (37.7 %). Conclusion This study provides new evidence of the safety and effectiveness of transarterial chemoembolization using doxorubicin-loaded microspheres for the treatment of hepatocellular carcinoma in patients who are not eligible for other treatments, or as a bridging treatment in patients on the liver transplant waiting list.

8 pages, 4 figures, 3 tables, Plant-based whole foods provide thousands of bioactive metabolites to the human diet that reduce the risk of developing chronic diseases. β-Caryophyllene (CAR) is a common constituent of the essential oil of numerous plants, vegetables, fruits and medicinal herbs, and has been used as a flavouring agent since the 1930 s. Here, we report the antioxidant activity of CAR, its protective effect on liver fibrosis and its inhibitory capacity on hepatic stellate cell (HSC) activation. CAR was tested for the inhibition of lipid peroxidation and as a free radical scavenger. CAR had higher inhibitory capacity on lipid peroxidation than probucol, a-humulene and a-tocopherol. Also, CAR showed high scavenging activities against hydroxyl radical and superoxide anion. The activity of 5-lipoxygenase, an enzyme that actively participates in fibrogenesis, was significantly inhibited by CAR. Carbon tetrachloride-treated rats received CAR at 2, 20 and 200 mg/kg. CAR significantly improved liver structure, and reduced fibrosis and the expression of Col1a1, Tgfb1 and Timp1 genes. Oxidative stress was used to establish a model of HSC activation with overproduction of extracellular matrix proteins. CAR (1 and 10 mM) increased cell viability and significantly reduced the expression of fibrotic marker genes. CAR, a sesquiterpene present in numerous plants and foods, is as a natural antioxidant that reduces carbon tetrachloride-mediated liver fibrosis and inhibits hepatic cell activation., The authors are grateful to the Spanish Ministry of Public Health for providing funds during the tenure of research.

Chronic kidney disease (CKD) is a worldwide major public health problem associated with increased risk of mortality and rate of hospitalization and decreased life expectancy. Progression from early to late stages of CKD generally results in the onset of new symptoms and concomitant complications. Frequent complications and comorbidities of CKD include fluid and electrolyte abnormalities, secondary hyperparathyroidism and renal osteodystrophy (known as Chronic Kidney Disease-Bone Mineral Disorder – CKD-BMD), hypertension and hyperlipidemia, anemia, metabolic acidosis, and several other comorbidities involving malnutrition, pruritus, and uremic bleeding. CKD patients are at increased risk of cardiovascular disease (CVD), which includes coronary heart disease (CHD), cerebrovascular disease, peripheral vascular disease, and heart failure. The management and prevention of these comorbidities, as well as the kidney transplant complications, are complex.

Osteoporosis is a systemic skeletal disease characterised by low bone mass and deterioration in the microstructure of bone tissue, which causes bone fragility and consequent increase in fracture risk. The lifetime fracture risk of a patient with osteoporosis is as high as 40 %, and fractures most commonly occur in the hip, spine or wrist. From a patient’s perspective, a fracture and the subsequent loss of mobility and autonomy often represent a major drop in the quality of life. Additionally, osteoporotic fractures of the hip and spine carry a 12-month excess mortality of up to 20 %, because they require hospitalisation and they subsequently present enhanced risk of other complications, such as pneumonia or thromboembolic disease due to chronic immobilisation.

Coumarin derivates have been considered an ideal target of personalized medicine because of their pharmacological characteristics as vitamin K antagonists. Thus, many pharmacogenetic investigators have focused in this field, developing numerous warfarin algorithms based on CYP2C9 and VKORC1 genotypes. These pharmacogenetic algorithms include both genetic and nongenetic factors.

Opiate and alcohol addiction are serious health and social problems, associated with high morbidity and mortality. The manifestation and development of these complex diseases involves genetic factors, environmental factors, and the pharmacokinetic and pharmacodynamic properties of the psychoactive substance.