Desarrollo de una taxonomía de las intervenciones farmacéuticas en pacientes VIH+ basados en el modelo CMO

Objective: To agree on a proposal for pharmaceutical interventions and establish their classification taxonomy according to the CMO-Pharmaceutical Care Model (Capacity-Motivation- Opportunity). Method: A study conducted between March and May, 2016. Two phases of development were defined. A literature review was initially conducted. Then, the DELPHI-Rand-UCLA methodology was used in order to reach a consensus about those interventions selected, and to define the taxonomy. Fifteen (15) experts, specialists in Pharmaceutical Care for HIV+ patients, were selected. This selection was explicitly conducted, following a protocol in order to avoid any bias. An initial proposal was developed according to the interventions extracted from Phase 1. These were tentatively classified according to the CMO Model, in a category based on their design and utility. Three issues were raised from the initial question: Do you agree with the proposed classification? If not, there was an option to re-categorize. Additionally, they were asked about the importance, priority and impact to achieve pharmacotherapeutic objectives that they would assign to it. Interventions were classified according to the degree of agreement. Once a consensus was reached, the final taxonomy was established. Results: Eighteen (18) articles were finally considered. The initial proposal included 20 pharmaceutical interventions with the following classification: seven in Capacity, eight in Motivation, and five in Opportunity. Those interventions considered to have greater importance and priority were: Review and Validation, Safety, and Adherence. The interventions with the greatest impact were: Review and Validation, Coordination, Adherence, and Motivation. On the other hand, the lowest scores for importance were for: Planning and Social Coordination; and in terms of impact: Social Coordination. Conclusions: The taxonomy reached by consensus will allow to classify pharmaceutical interventions with the new model, and therefore to conduct an improved research and patient care

El reto del envejecimiento y la complejidad farmacoterapéutica en el paciente VIH+

Objective: To describe the current knowledge and management of aging and pharmacotherapeutic complexity in HIV + patients. Method: A review of literature was carried out, including articles, originals or reviews, published in English or Spanish, from 2007 to 2017, which analysed the aging and pharmacotherapeutic complexity in HIV + patients. The terms «Polypharmacy»/«Polifarmacia», «Aging»/«Envejecimiento», «Frailty»/«Fragilidad», «Complejidad Farmacotera péutica»/«Medication Regimen Complexity» and «HIV»/«VIH» were combined. The review was carried out independently by two authors. The degree of agreement, according to the Kappa index, was analysed. Results: A total of 208 references were analysed, including, finally, only 68. An aging of the population and an increase in associated comorbidities have been identified, especially over 50 years-old. Immunological changes similar to those that are generated in a non-infected elderly population have been described. These conditions influencing the prescription of antiretroviral treatment, according to studies identified. In parallel, polypharmacy is increasingly present, being defined exclusively by the concomitant use of five drugs. Pharmacotherapeutic complexity, through the Medication Regimen Complexity Index, has begun to analyse and relate to health outcomes. There has been a need to know and apply concepts already known in non-HIV-aged population, such as deprescription, potentially inappropriate medication, cholinergic risk, although few results are available. Conclusions: There is a growing interest to know about the relationship between HIV and aging. Pharmacotherapeutic complexity is beginning to be used as a pharmacotherapeutic follow-up criterion due to its influence on health outcomes. It is necessary to manage and incorporate new concepts that help pharmacotherapeutic optimization in this population

Therapeutical interest of statins in the treatment of atherosclerosis

Los inhibidores de la HMG-Co A reductasa o estatinas, son fármacos muy utilizados en el tratamiento de la hipercolesterolemia, ya que consiguen disminuir la concentración plamática de lipoproteína de baja densidad (LDL) regulando la síntesis endógena de colesterol y por tanto, de receptores para LDL. Recientemente se ha comprobado como el tratamiento prolongado con estos fármacos disminuyen la mortalidad y morbilidad cardiovascular. Este fenómeno puede explicarse por los efectos beneficiosos directos de las estatinas en el desarrollo de la placa de ateroma. Las estatinas disminuyen la proliferación y migración de células de musculatura lisa vascular e inducen apoptosis de estas células. También previenen la oxidación de LDL y la formación de células espumosas, reducen la respuesta inflamatoria asociada a la aterosclerosis, normalizan los fenómenos de coagulación y fibrinolisis y por último mejoran significativamente la función endotelial. Todas estas propiedades parecen estar mediadas compuestos isoprenoides intermediarios de la ruta metabólica de la HMG-Co A reductasa, y son indepen- dientes de la concentración de colesterol en el medio. Por tanto, las estatinas también podrían ser utilizadas en enfermedades asociadas a disfunción endotelial indepen- dientemente de las cifras analíticas de LDL, tal y como sucede en la hipertensió

Effects of pomace olive oil-enriched diets on endothelial function of small mesenteric arteries from spontaneously hypertensive rats

Pomace olive oil (POM), an olive oil subproduct traditionally used in Spain, is a good source of minor components from the unsaponifiable fraction such as triterpenoids, mainly in the form of oleanolic acid, which induces vascular protection and vasodilatation. Our aim was to evaluate the effects of long-term intake of diets enriched in POM with high concentration in oleanolic acid on endothelial dysfunction associated to hypertension in small mesenteric arteries (SMA) from spontaneously hypertensive rats (SHR). During 12 weeks, rats (six rats per group) were fed either a control 2% maize oil diet (BD), or high-fat diets containing 15% refined olive oil (OL), pomace olive oil (POM), or pomace olive oil supplemented in oleanolic acid (POMO; up to 800 parts per million). Endothelial and vascular functions were assessed by relaxing or contracting responses to acetylcholine (ACh) or phenylephrine, respectively. The involvement of endothelium-derived relaxing factors in these responses was evaluated. In contrast to BD, SHR fed high-fat diets showed a biphasic response to ACh related to changes in eicosanoid metabolism. POM enhanced the endothelial function in SMA from SHR by increasing the endothelium-derived hyperpolarising factor (EDHF)-type component, whereas administration of POMO resulted in a similar contribution of NO/EDHF in the endothelial response to ACh. The present study shows that despite the lack of changes in blood pressure, consumption of POM improves endothelial function in SMA from SHR by improving the agonist-mediated EDHF/NO response. Thus, triterpenoids confer a protective role to POM against endothelial dysfunction in hypertension.Comision Interministerial de Ciencia y Tecnologia AGR163Junta de Andalucia AGL2005-00 572, AGL2008-022845/ALIFondo de Investigaciones Sanitarias ISCIII G03/140-200

Endothelium modulates contractile response to simvastatin in rat aorta

Simvastatin is an inhibitor of HMG-CoA reductase used in the treatment of hypercholesterolemia. In the present study simvastatin-induced contraction was observed in rat aortic thoracic rings, this effect increased when the endothelium was removed and when NO synthase was blocked by L-NOARG (3 x 10-5 M). The contractile effect of simvastatin on intact aortic rings diminished when cyclo-oxygenase was inhibited with indomethacin (10-5 M). Also in the presence of endothelium, pretreatment with mevalonate (1 mM), the product of HMGCoA reductase activity, significantly inhibited the contraction. In other experiments carried out on endothelium-removed preparations and in medium containing the calcium antagonist, diltiazem (10-5 and 10-6 M), the contraction dose-response curves were significantly reduced and the same happened in the presence of the inhibitor of sarcoplasmic reticulum Ca-2+ATPase, cyclopiazonic acid (CPA) (3 x 10-6 M). The results suggest that simvastatin might increase intracellular calcium concentration. This effect could lead to an activation of NO synthase and cyclooxygenase pathways in endothelial cells and to contraction in vascular smooth muscle cells. This rise in Ca2+ concentration could be due to an inhibition of isoprenoid synthesis prevented by mevalonate

Oral supplementation of propionyl-l-carnitine reduces body weight and hyperinsulinaemia in obese Zucker rats

Propionyl-l-carnitine (PLC) is an SCFA esterified to carnitine that plays an important role in fatty acid oxidation and energy expenditure, in addition to having a protective effect on the endothelium. In order to evaluate the effect of PLC on an animal model of obesity, insulin resistance and, consequently, endothelial dysfunction, lean and obese Zucker rats (OZR) received either vehicle- or PLC-supplemented drinking water (200mg/kg per d) for 20 weeks. Body weight, food intake, systolic blood pressure and heart rate were controlled weekly and an oral glucose tolerance test was performed. Fasting glucose, TAG, cholesterol, HDL, NEFA, adiponectin and insulin were analysed in serum. Visceral adipose tissue and liver were weighed and liver TAG liver composition was evaluated. Endothelial and vascular functions were assessed in the aorta and small mesenteric arteries by response to acetylcholine, sodium nitroprusside and phenylephrine (Phe); NO participation was evaluated after incubation with the NO synthase (NOS) inhibitor NG-nitro-l-arginine methyl ester (l-NAME) and endothelial NOS protein expression by Western blotting. PLC decreased body-weight gain, food intake, adiposity, insulin serum concentration and TAG liver content and improved insulin resistance. Aortae from OZR receiving either vehicle or PLC exhibited a lower contractile response to Phe. PLC-treated OZR showed an enhanced release of endothelial NO upon the adrenergic stimulation. The protection of vascular function found after treatment with PLC in an animal model of insulin resistance supports the necessity of clinical trials showing the effect of l-carnitine supplements on metabolic disorders.Junta de Andalucía CTS-17

Analysis of the implementation of GESIDA quality indicators in the HIV+ cohort PSITAR

Objective: To determine the compliance of quality care indicators (GESIDA) for adult patients living with HIV infection in PSITAR cohort. Methods: Multi-center, prospective observational study. All adult naive patients, that began treatment during 2011 belonging to the PSITAR cohort, were selected. We recorded demographic data, virological parameters at baseline and 48 weeks of treatment and pharmacotherapy variables. The selected indicators were: The compliance of initial antiretroviral therapy with the Spanish national treatment guidelines (GESIDA) for treatment-naive HIV-infected patient (95%), undetectable viral load at 48 weeks (80%), treatment initiation with Abacavir without screening for HLA-B*5701 (0%), treatment modifications within the first year (<30%), adherence treatment measure (95%), study of resistance in the virologic failure (90%) and average expenditure per patient in the first treatment (GESIDA median). Results: In total 108 HIV+ naive patients were included, 83.3% men. The median age was 40.5 years (21-75). The most frequent combination was tenofovir-emtricitabineefavirenz with 61.0%. 28 patients (29.7%) modified their treatment during the first year. Focusing on indicators compliance, starting of treatment with a recommended regimen had 95.4% of compliance, undetectable viral load indicator 74.1%, treatment initiation without Abacavir test 0%, treatment modifications within the first year 25.9%, adherence treatment measure 86.3%, study of resistance in the virologic failure 80% and average expenditure per patient was 8,846 euros. Conclusion: Quality care follow up indicators were fulfilled in their vast majority. The worst accomplished indicators such as undetectable viral load at 48 weeks, evaluation of adherence and study of resistance must be study to examine the possible improvement points.Objetivos: Determinar el cumplimiento de los indicadores de calidad de la actividad asistencial GESIDA en la cohorte de pacientes VIH+ PSITAR. Método: Estudio multicéntrico prospectivo. Se seleccionaron aquellos pacientes VIH naive adulto que iniciaron tratamiento en 2011. Se recogieron variables demográficas, analíticas y farmacoterapéuticas. Los indicadores seleccionados fueron: adecuación de las pautas iniciales de TAR a las guías españolas (95%), carga viral indetectable al año de tratamiento (80%), tratamiento con abacavir sin HLA-B*5701 previo (0%), cambios de tratamiento durante el primer año (<30%), registro de la adherencia al tratamiento (95%), estudio de resistencias en el fracaso virológico (90%) y gasto medio por paciente en primer tratamiento (mediana GESIDA). Resultados: Se incluyeron 108 pacientes, de ellos el 83,3% hombres. La mediana de edad fue de 40,5 años (21-75). La combinación de inicio más frecuente fue emtricitabina-tenofovir-efavirenz (61%). El 95,4% de los pacientes iniciaron con un tratamiento considerado preferente. El 74,1% presentó carga viral plasmática indetectable a las 48 semanas. Ningún paciente inicio tratamiento con abacavir sin la determinación del HLA-B*5701. El 25,9% discontinuó el TAR en el primer año, registrándose una valoración de la adherencia en el 86,3% de los casos. El estudio de las resistencias en fallo virológico se realizó en el 80,0% de los pacientes y el gasto medio fue de 8.846 euros. Conclusiones: Los indicadores de calidad de la actividad asistencial se cumplen ampliamente. La carga viral plasmática indetectable, la valoración de la adherencia y el estudio de resistencia requieren de un mayor estudio para detectar puntos de mejora

Pomace Olive Oil Concentrated in Triterpenic Acids Restores Vascular Function, Glucose Tolerance and Obesity Progression in Mice

Pomace olive oil, an olive oil sub-product, is a promising source of bioactive triterpenoids such as oleanolic acid and maslinic acid. Considering the vascular actions of pomace olive oil and the potential effects of the isolated oleanolic acid on metabolic complications of obesity, this study investigates for the first time the dietary intervention with a pomace olive oil with high concentrations of the triterpenic acids (POCTA), oleanolic and maslinic acid, during diet-induced obesity in mice. The results demonstrate that obese mice, when switched to a POCTA-diet for 10 weeks, show a substantial reduction of body weight, insulin resistance, adipose tissue inflammation, and particularly, improvement of vascular function despite high caloric intake. This study reveals the potential of a functional food based on pomace olive oil and its triterpenic fraction against obesity progression. Our data also contribute to understanding the health-promoting effects attributable to the Mediterranean dietSpanish Ministerio de Economía, Industria y Competitividad (MINECO), Agencia Estatal de Investigación (AEI), and Fondo Europeo de Desarrollo Regional (FEDER) (Grants SAF2017-82813-C3-3-R and PCI2018-092997/AEI to R.R.-R.

Endothelium-dependent vasorelaxation induced by L-carnitine in isolated aorta from normotensive and hypertensive rats

The aim of this work was to investigate the mechanism of the vasodilatory effect induced by L- carnitine. Relaxation produced by L-carnitine was studied in rat aortic rings with and without functional endothelium, pre-contracted with phenylephrine by adding cumulative doses of L- carnitine (10-7 to 10-3 M). The relaxation evoked by L-carnitine reached higher values in aortic rings from spontaneously hypertensive rats than those obtained in arteries from normotensive rats; no relaxation was produced in de-endothelialized arteries. However, in the presence of NG-nitro-L- arginine (3¬10-5 M, a nitric oxide synthase inhibitor), Ro 68070 (10-4 M, a thromboxane synthetase inhibitor–thromboxane A2/prostaglandin H2 receptor antagonist) or ICI 192605 (10- M, a thromboxane A2 receptor antagonist) the relaxant response to L-carnitine was signiicantly inhibited. These results show that L-carnitine induced endothelium-dependent relaxation in the rat aorta and the mechanism of this relaxation appeared to be mostly mediated by endothelial production of nitric oxide but also could involve prevention of the action of cyclooxygenase endothelial products acting on the thromboxane A2/prostaglandin H2 receptor