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1.
Ars pharm ; 62(1): 15-39, ene.-mar. 2021. ilus, tab, graf
Artigo em Espanhol | IBECS-Express | IBECS | ID: ibc-ET6-1766

RESUMO

INTRODUCCIÓN: Los errores de medicación se encuentran entre las 10 principales causas de muerte en el mundo y en su mayoría son prevenibles. Los servicios profesionales farmacéuticos asistenciales (SPFA) tratan de garantizar un uso más seguro, efectivo y eficiente de los medicamentos, y por ello los farmacéuticos comunitarios pueden contribuir a reducir errores de la medicación a nivel de atención primaria. Este trabajo pretender ofrecer un marco de evidencia sobre las iniciativas llevadas a cabo por farmacéuticos comunitarios, a nivel estatal, para identificar, reducir o eliminar los errores de medicación en los diferentes puntos de la cadena terapéutica y plantear una revisión, de los puntos críticos de la cadena terapéutica y clasificar los SPFA. MÉTODO: Revisión sistemática exploratoria de bases de datos internacionales y estatales para obtener estudios publicados sobre la intervención del farmacéutico en la detección, reducción o eliminación de los errores de medicación. RESULTADOS: Se han recopilado 39 iniciativas que se han clasificado en 7 puntos críticos de la cadena terapéutica: (I) 7 en dispensación, (II) 4 en validación o revisión del tratamiento, (III) 3 en transición asistencial, (IV) 18 en monitorización del tratamiento, (V) 4 en educación a pacientes y (VI) 3 en indicación. CONCLUSIONES: Los SPFA llevados a cabo a nivel estatal demuestran que sirven para identificar y resolver los errores de medicación y se plantea una nueva clasificación de los 7 puntos de la cadena terapéutica que se identifican como críticos para la farmacia comunitaria y los relaciona con los SPFA que intervienen en cada uno de los puntos


INTRODUCTION: Medication errors, mostly preventable, are among the top 10 causes of death worldwide. Commu¬nity pharmacists provide professional pharmacy services (PPS) to ensure safer, more effective and efficient use of medications, being professionals who should be included in strategies to reduce medication errors at the primary care level. This work aims to offer an evidence framework on the initiatives carried out by community pharmacists, in Spain, to identify, reduce or eliminate medication errors at different points in the therapeutic chain and propose a classification of the critical points of the therapeutic chain to classify PPS. METHOD: Scoping review of international and national databases to obtain published studies where the community pharmacists provide an intervention to detect, reduce or eliminate of medication errors. RESULTS: 39 records have been compiled and have been classified in 7 critical points of the therapeutic chain: (I) 7 in dispensation, (II) 4 in validation/review of the treatment, (III) 3 in healthcare transition, (IV) 18 in treatment monitor¬ing, (V) 4 in education to patients and (VI) 3 in minor ailments service. CONCLUSIONS: The PPS carried out at the state level demonstrate that they serve to identify and resolve medication errors and a new classification of the critical points of the therapeutic chain that exist in the community pharmacy is proposed, and it relates to the PPS that are involved in each point

2.
Aten. prim. (Barc., Ed. impr.) ; 53(1): 43-50, ene. 2021. tab, graf
Artigo em Inglês | IBECS-Express | IBECS | ID: ibc-ET6-1867

RESUMO

OBJECTIVE: To estimate the effectiveness of a Medication Discrepancy Detection Service (MDDS), a collaborative service between the community pharmacy and Primary Care. DESIGN: Non-controlled before-and-after study. SETTING: Bidasoa Integrated Healthcare Organisation, Gipuzkoa, Spain. PARTICIPANTS: The service was provided by a multidisciplinary group of community pharmacists (CPs), general practitioners (GPs), and primary care pharmacists, to patients with discrepancies between their active medical charts and medicines that they were actually taking. Outcomes: The primary outcomes were the number of medicines, the type of discrepancy, and GPs' decisions. Secondary outcomes were time spent by CPs, emergency department (ED) visits, hospital admissions, and costs. RESULTS: The MDDS was provided to 143 patients, and GPs resolved discrepancies for 126 patients. CPs identified 259 discrepancies, among which the main one was patients not taking medicines listed on their active medical charts (66.7%, n = 152). The main GPs' decision was to withdraw the treatment (54.8%, n = 125), which meant that the number of medicines per patient was reduced by 0.92 (9.12 ± 3.82 vs. 8.20 ± 3.81; p < .0001). The number of ED visits and hospital admissions per patient were reduced by 0.10 (0.61 ± .13 vs 0.52 ± 0.91; p = .405 and 0.17 (0.33 ± 0.66 vs. 0.16 ± 0.42; p = .007), respectively. The cost per patient was reduced by (Euro)444.9 ((Euro)1003.3 ± 2165.3 vs. (Euro)558.4 ± 1273.0; p = .018). CONCLUSION: The MDDS resulted in a reduction in the number of medicines per patients and number of hospital admissions, and the service was associated with affordable, cost-effective ratios


OBJETIVOS: Estimar la efectividad del servicio de detección de discrepancias de la medicación, un servicio de colaboración entre la farmacia comunitaria y la atención primaria. DISEÑO: Estudio de intervención antes-después, sin grupo control. Emplazamiento: Organización Sanitaria Integrada de Bidasoa, Gipuzkoa, España. PARTICIPANTES: El servicio fue ofrecido por un grupo multidisciplinar que incluía farmacéuticos comunitarios (FC), médicos de atención primaria (MAP) y farmacéuticos de atención primaria a pacientes que presentaban discrepancias entre la medicación prescrita en la hoja de tratamiento activo y lo que realmente estaban tomando. Mediciones principales: Las variables principales del estudio fueron el número de medicamentos, tipo de discrepancia y la decisión del MAP. Las variables secundarias fueron tiempo invertido por el farmacéutico, visitas al servicio de urgencias, ingresos hospitalarios y los costes. RESULTADOS: El servicio se ofreció a 143 pacientes, y el MAP resolvió las discrepancias de un total de 126 pacientes. El FC identificó 259 discrepancias de las cuales la mayoría fue que el paciente no estaba tomando un medicamento prescrito (66,7%, n = 152). En la mayoría de los casos, la decisión del MAP fue suspender el tratamiento (54,8%, n = 125); el número de medicamentos que tomaba el paciente se redujo en un 0,92 (9,12 ± 3,82 vs. 8,20 ± 3,81; p < 0,0001). El número de visitas al hospital y los ingresos hospitalarios se redujeron en 0,10 (0,61 ± 0,13 vs. 0,52 ± 0,91; p = 0,405) y 0,17 puntos (0,33 ± 0,66 vs. 0,16 ± 0,42; p = 0,007), respectivamente. El coste por paciente se redujo en 444,9 (Euro) (1.003,3 ± 2.165,3 vs. 558,4 (Euro) ± 1.273,0; p = 0,018). CONCLUSIÓN: El servicio redujo el número de medicamentos que tomaba el paciente e ingresos hospitalarios y esto se relacionó con unos ratios de coste-efectividad positivos

3.
Aten Primaria ; 2020 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-32994060

RESUMO

OBJECTIVE: To estimate the effectiveness of a Medication Discrepancy Detection Service (MDDS), a collaborative service between the community pharmacy and Primary Care. DESIGN: Non-controlled before-and-after study. SETTING: Bidasoa Integrated Healthcare Organisation, Gipuzkoa, Spain. PARTICIPANTS: The service was provided by a multidisciplinary group of community pharmacists (CPs), general practitioners (GPs), and primary care pharmacists, to patients with discrepancies between their active medical charts and medicines that they were actually taking. OUTCOMES: The primary outcomes were the number of medicines, the type of discrepancy, and GPs' decisions. Secondary outcomes were time spent by CPs, emergency department (ED) visits, hospital admissions, and costs. RESULTS: The MDDS was provided to 143 patients, and GPs resolved discrepancies for 126 patients. CPs identified 259 discrepancies, among which the main one was patients not taking medicines listed on their active medical charts (66.7%, n=152). The main GPs' decision was to withdraw the treatment (54.8%, n=125), which meant that the number of medicines per patient was reduced by 0.92 (9.12±3.82 vs. 8.20±3.81; p<.0001). The number of ED visits and hospital admissions per patient were reduced by 0.10 (0.61±.13 vs 0.52±0.91; p=.405 and 0.17 (0.33±0.66 vs. 0.16±0.42; p=.007), respectively. The cost per patient was reduced by €444.9 (€1003.3±2165.3 vs. €558.4±1273.0; p=.018). CONCLUSION: The MDDS resulted in a reduction in the number of medicines per patients and number of hospital admissions, and the service was associated with affordable, cost-effective ratios.

4.
J Eval Clin Pract ; 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32881191

RESUMO

INTRODUCTION: Non-adherence is a major problem among patients with chronic diseases. Community pharmacists are ideally positioned to detect non-adherence and to provide patient-centred interventions. OBJECTIVE: To conduct a systematic review of the impact of community pharmacist interventions on patient adherence to lipid lowering medication (LLM) prescriptions and clinical outcomes. SEARCH METHOD: Five databases (MEDLINE, Cochrane Library, Science Direct, Scopus, and Web of Knowledge) were searched systematically to identify relevant reports published by December 2019. Study quality was assessed with the Cochrane risk of bias (RoB 2.0) tool. SELECTION CRITERIA: Controlled trials in which community pharmacists conducted an intervention to improve patient adherence to LLM and clinical outcomes were evaluated. MAIN RESULTS: Five studies (2408 participants) were included in the qualitative analysis. Four studies (n = 2266) were pooled in the meta-analysis. Participants in the intervention group (IG) had better adherence than those in the control group (CG) [odds ratio (OR) = 1.67; 95% confidence interval (CI) 1.38-2.02; P < 0.001; I2 = 54%]. Better adherence rates were obtained when adherence was measured with validated questionnaires than when medication-possession ratio (MPR) measurements were used. Total cholesterol (TC) levels were not included in the meta-analysis due to data variability among the studies. CONCLUSIONS: Pharmacist-led intervention can improve LLM adherence, but its influence on clinical outcomes, including lipid level control, remains to be clarified.

5.
Int J Clin Pharm ; 42(2): 331-335, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32301066

RESUMO

Background Non-adherence is a problem that particularly affects those with chronic diseases. Studying causes for not following the treatment is necessary to choose the best intervention to improve non-adherence. Objective Analyze how the intentionality of non-adherence modulates the effects of professional intervention in patients with hypercholesterolemia. Setting: Community pharmacies and primary care centres in Spain. Methods A 6-month randomized controlled trial was conducted in 46 community pharmacies and 50 primary care centres in Spain. Adherence to statin therapy was measured with the Morisky-Green-Levine test. Non-adherence was classified based on the intentionality. Results 746 Patients were recruited for the study (465 non-adherent and 281 adherent). Of those, 237 were randomly assigned to the intervention group and 228 to the non-intervention group. The 56.5% of non-adherent patients were classified as unintentional non-adherents and 43.5% as intentional non-adherents. More patients in the intervention group finished being adherent compared with the non-intervention group (+ 17.2% for intentional non-adherents and + 27.4% for unintentional non-adherence). The percentage of patients in the intervention group who completed the study as adherent was higher among those who previously had unintentional non-adherence (66.4%) compared to those with intentional non- adherence (55.3%) (p < 0.001). Conclusion Intervention provided to patients with unintentional non-adherence was more effective than intervention provided to patients with intentional non- adherence.

6.
Health Serv Res ; 54(3): 658-668, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30957240

RESUMO

OBJECTIVE: To evaluate the impact of health professionals' intervention on adherence to statins, the influence on total cholesterol levels, and lifestyle patterns in patients with hypercholesterolemia and analyze the differences according to the center of recruitment. STUDY SETTING: Forty-six community pharmacies and 50 primary care centers of Spain. STUDY DESIGN: Randomized controlled trial design (n = 746). Patients were assigned into adherent (ADH) or nonadherent group depending on their initial adherence to statins. Nonadherent patients were randomly assigned to intervention (INT) or nonintervention (NOINT) group. Patients enrolled in the INT group received an intervention depending on the cause of nonadherence. Patients in the ADH and NOINT groups received usual care. Intention-to-treat (ITT) analysis was performed with multiple imputation to replace the missing data. DATA COLLECTION: Adherence, total cholesterol levels, and lifestyle behaviors. FINDINGS: The odds of becoming adherent during the 6 months was higher in the INT group compared to the NOINT group (OR = 1,49; 95% CI: 1.30-1.76; P < 0.001), especially in the community pharmacy group (OR = 2.34; 95% CI: 1.81-3.03; P < 0.001). Adherent patients showed lower values of total cholesterol compared with nonadherent patients at baseline (ADH: 200.3 mg/dL vs NOADH: 216.7 mg/dL; P < 0.001) and at the endpoint (ADH: 197.3 mg/dL vs NOADH: 212.2 mg/dL; P < 0.001). More patients enrolled in the INT group practices exercise at the end of the study (INT: +26.6 percent; P = 0.002), and a greater number of patients followed a diet to treat hypercholesterolemia (+30.2 percent; P < 0.001). CONCLUSIONS: The intervention performed by health professionals, especially by community pharmacists, improved adherence to statins by hypercholesterolemic patients, and this improvement in adherence was accompanied by a reduction in total cholesterol levels and a healthier lifestyle.


Assuntos
Clínicos Gerais/organização & administração , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Farmacêuticos/organização & administração , Idoso , Colesterol/sangue , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Fatores Socioeconômicos , Espanha
7.
Int J Pharm Pract ; 27(1): 25-33, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29693292

RESUMO

INTRODUCTION: The Global Network of Age-friendly Cities is a project promoted by the World Health Organization as a response to demographic ageing and urbanization process. San Sebastian, Spain, is one of these Age-friendly Cities and community pharmacies of the city joined the initiative. OBJECTIVE: To define and implement the Age-friendly Pharmacy concept to promote active ageing, optimize the contribution of community pharmacies of San Sebastian to the friendliness of the city and to the improvement of quality of life of the ageing population. METHOD: A bottom-up participative approach was undertaken. A focus group was conducted to determine elderly people's opinions and expectations of community pharmacy. The information obtained was analysed using content analysis and validated for reliability, usefulness and applicability through three expert groups of community pharmacy owners and staff. KEY FINDINGS: Fifteen requirements were agreed, covering four main areas: relationships, pharmacy layout, pharmaceutical services and communication of services. Initially, 18 community pharmacies committed to become Age-friendly Pharmacies by pledging to these requirements and the Official Pharmacist Association of Gipuzkoa supported pharmacies in the implementation of the initiative. CONCLUSION: This study suggests that there is demand for a patient-centred community pharmacy to support older people, in which pharmaceutical care services are required. The 18 Age-friendly Pharmacies together with the Official Pharmacist Association of Gipuzkoa have publicly committed to actively work on social and patient-centred care to meet the needs of the ageing population.


Assuntos
Serviços Comunitários de Farmácia/organização & administração , Envelhecimento Saudável , Farmácias/organização & administração , Pesquisa Qualitativa , Qualidade de Vida , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Grupos Focais , Necessidades e Demandas de Serviços de Saúde/organização & administração , Humanos , Masculino , Pessoa de Meia-Idade , Assistência Centrada no Paciente/métodos , Assistência Centrada no Paciente/organização & administração , Reprodutibilidade dos Testes , Espanha
8.
Nutr Neurosci ; 21(1): 70-78, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27603597

RESUMO

BACKGROUND: Lifestyle, including dietary patterns, could involve specific factors participating in inflammation that confer a higher risk of suffering a stroke. However, little attention has been apparently given to habitual food consumption in patients suffering a cerebrovascular event. OBJECTIVE: To assess the influence of dietary habits as well as other lifestyle-related variables on the risk of suffering a stroke. DESIGN: A case-control study was designed. Fifty-one cases (age: 59.1 ± 9.1y.o; BMI; 30.8 ± 3.4 kg/m2) and 51 controls (age: 61.1 ± 9.1y.o; BMI; 30.4 ± 3.6 kg/m2) were enrolled in the study. Anthropometric and body composition variables were measured. Dietary information was obtained from a validated food frequency questionnaire. Physical activity and lifestyle-related factors were assessed. Blood samples were drawn. RESULTS: Patients suffering a stroke showed higher prevalence of diabetes (30 vs. 7.7%; P = 0.020) and hypertension (74.5 vs. 40.3%; P < 0.001) and were less physically active (36.7 vs. 66.6%; P = 0.024) than controls. Patients registered worse glucose and lipid profiles, higher levels of hepatic biomarkers, and higher blood cell counts than controls. Stroked patients showed lower adherence to a statistically derived healthy dietary pattern than controls (23.5 vs. 42.3%; P = 0.017). A logistic regression model was built up considering hypertension, diabetes, smoking, physical activity, adherence to a 'healthy dietary pattern' and C-reactive protein concentration. The final model strongly associated with the risk of suffering a stroke (R2: 44.6%; Pmodel < 0.0001). CONCLUSION: Lifestyle variables such as physical activity, smoking habit, and a dietary pattern including foods with low inflammatory potential play an important role in the reduction of the risk of suffering a stroke.


Assuntos
Dieta , Estilo de Vida , Acidente Vascular Cerebral/epidemiologia , Idoso , Biomarcadores/sangue , Pressão Sanguínea , Composição Corporal , Índice de Massa Corporal , Estudos de Casos e Controles , Diabetes Mellitus/epidemiologia , Exercício Físico , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Acidente Vascular Cerebral/sangue , Inquéritos e Questionários
9.
Res Social Adm Pharm ; 13(3): 614-627, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27423785

RESUMO

Pharmacist-led medication review services are recognized as a key to medicines management. This case study describes the implementation process of a medication review with follow-up service in a community pharmacy setting and evaluates its initial outcomes. An implementation-effectiveness hybrid study was undertaken in a community pharmacy setting. The implementation process was divided into four different phases: Exploration and adoption, program installation, initial implementation, and full operation. A core set of implementation outcomes was measured, including penetration, implementation costs, feasibility, fidelity, acceptability, appropriateness and efficiency. The penetration rate of the service was nearly 62.5%, and the implementation costs were 57,359.67€. There was a high retention-participation rate of patients. For every month of service provision, there was a 1.27 increase in the number of patients requesting the service, compared to the number of patients being offered the service. The time spent on service provision was 171.7 min per patient. Average patient satisfaction with the service was 4.82 (SD: 0.39, scale 1-5), and the acceptance rate of care plans by patients and general medical practitioners were 96.99% and 96.46%, respectively. There were 408 negative outcomes associated with the use of medications were identified during the study (3.09 per patient), of which 96.3% were resolved. The average time per patient spent on service provision significantly decreased along the 18 months of service provision. This case report can assist individual pharmacists and professional organizations interested in implementing evidence-based services by offering an example on how to approach the implementation process in a systematic way.


Assuntos
Serviços Comunitários de Farmácia/organização & administração , Conduta do Tratamento Medicamentoso/organização & administração , Satisfação do Paciente , Farmacêuticos/organização & administração , Humanos , Papel Profissional , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Fatores de Tempo
10.
Eur J Health Econ ; 18(9): 1069-1078, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27913940

RESUMO

BACKGROUND: Drug related problems have a significant clinical and economic burden on patients and the healthcare system. Medication review with follow-up (MRF) is a professional pharmacy service aimed at improving patient's health outcomes through an optimization of the medication. OBJECTIVE: To ascertain the economic impact of the MRF service provided in community pharmacies to aged polypharmacy patients comparing MRF with usual care, by undertaking a cost analysis and a cost-benefit analysis. METHODS: The economic evaluation was based on a cluster randomized controlled trial. Patients in the intervention group (IG) received the MRF service and the comparison group (CG) received usual care. The analysis was conducted from the national health system (NHS) perspective over 6 months. Direct medical costs were included and expressed in euros at 2014 prices. Health benefits were estimated by assigning a monetary value to the quality-adjusted life years. One-way deterministic sensitivity analysis was undertaken in order to analyse the uncertainty. RESULTS: The analysis included 1403 patients (IG: n = 688 vs CG: n = 715). The cost analysis showed that the MRF saved 97 € per patient in 6 months. Extrapolating data to 1 year and assuming a fee for service of 22 € per patient-month, the estimated savings were 273 € per patient-year. The cost-benefit ratio revealed that for every 1 € invested in MRF, a benefit of 3.3 € to 6.2 € was obtained. CONCLUSION: The MRF provided health benefits to patients and substantial cost savings to the NHS. Investment in this service would represent an efficient use of healthcare resources.


Assuntos
Reconciliação de Medicamentos , Polimedicação , Anos de Vida Ajustados por Qualidade de Vida , Idoso , Análise Custo-Benefício , Seguimentos , Humanos , Farmácias
11.
Br J Clin Pharmacol ; 82(3): 831-8, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27195696

RESUMO

AIMS: The aims were to assess the impact of a medication review with follow-up (MRF) service provided in community pharmacy to aged polypharmacy patients on the number of medication-related hospital admissions and to estimate the effect on hospital costs. METHODS: This was a sub-analysis of a cluster randomized controlled trials carried out in 178 community pharmacies in Spain. Pharmacies in the intervention group (IG) provided a comprehensive medication review during 6 months. Pharmacists in the comparison group (CG) delivered usual care. For the purposes of this sub-analysis, an expert panel of three internal medicine specialists screened the hospitalizations occurring during the main study, in order to identify medication-related hospitalizations. Inter-rater reliability was measured using Fleiss's kappa. Hospital costs were calculated using diagnosis related groups. RESULTS: One thousand four hundred and three patients were included in the main study and they had 83 hospitalizations. Forty-two hospitalizations (50.6%) were medicine-related, with a substantial level of agreement among the experts (kappa = 0.65, 95% CI 0.52, 0.78, P < 0.01). The number of medication-related hospitalizations was significantly lower in patients receiving MRF (IG 11, GC 31, P = 0.042). The probability of being hospitalized was 3.7 times higher in the CG (odds ratio 3.7, 95% CI 1.2, 11.3, P = 0.021). Costs for a medicine-related hospitalization were €6672. Medication-related hospitalization costs were lower for patients receiving MRF [IG: €94 (SD 917); CG: €301 (SD 2102); 95% CI 35.9, 378.0, P = 0.018]. CONCLUSION: MRF provided by community pharmacists might be an effective strategy to balance the assurance of the benefit from medications and the avoidance of medication-related hospitalizations in aged patients using polypharmacy.


Assuntos
Serviços Comunitários de Farmácia/economia , Revisão de Uso de Medicamentos/economia , Hospitalização/estatística & dados numéricos , Polimedicação , Idoso , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Humanos , Masculino , Variações Dependentes do Observador , Espanha
12.
Curr Neurovasc Res ; 12(4): 321-33, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26238466

RESUMO

Ischemic stroke patients often show high concentrations of circulating inflammatory markers that are associated with increased risk of recurrence. Epigenetic mechanisms could be involved in obesity, inflammation and stroke. The objective of this research was to investigate, in obese patients suffering a previous stroke, the effects of a nutritional program on anthropometric and biochemical variables, and on the methylation patterns of two stroke-related genes (KCNQ1: potassium channel, voltage gated KQT-like subfamily Q, member 1; and WT1: Wilms tumor 1). Twenty-two ischemic stroke patients were compared with a control group composed of eighteen obese subjects with similar age and body mass index ranges. Both groups followed a 20-week nutritional program based on an energy-restricted balanced diet with high adherence to the Mediterranean dietary pattern. The intervention significantly improved anthropometric and metabolic variables, such as the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and C-reactive protein concentration, in ischemic stroke patients, and was accompanied by changes in the methylation patterns of both stroke-related genes, which correlated with anthropometric and biochemical variables.


Assuntos
Metilação de DNA/genética , Dieta Redutora/métodos , Canal de Potássio KCNQ1/genética , Obesidade , Acidente Vascular Cerebral , Proteínas WT1/genética , Idoso , Antropometria , Glicemia , Pressão Sanguínea , Composição Corporal , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , Epigênese Genética , Feminino , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/dietoterapia , Obesidade/genética , Fatores de Risco , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/genética
13.
Eur J Nutr ; 54(3): 365-75, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24903807

RESUMO

INTRODUCTION: There is still a scientific debate on the exact role played by obesity on stroke risk. OBJECTIVE: The aim of the study was to analyze the association between obesity, measured by different indices such as body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and a new one called A Body Shape Index (ABSI) and the risk of total and ischemic stroke. SUBJECTS/METHODS: A total of 41,020 subjects (15,490 men and 25,530 women) aged 29-69 years participated in the study. All participants were recruited between 1992 and 1996 and followed up until 2008 to ascertain incident cerebrovascular disease events. Cox proportional hazards models were designed to estimate the relative risk and 95% CI between obesity and cerebrovascular disease incidence. RESULTS: After 13.8 years of follow-up, a total of 674 stroke cases (55.3% in men) were registered (531 ischemic, 79 hemorrhagic, 42 subarachnoid hemorrhage and 22 unspecified). WC fourth quartile (HR 1.95; 95% CI 1.20-3.19) and WHR fourth quartile (HR 1.58; 95% CI 1.12-2.25) were positively associated with total stroke only in men. BMI was not associated with stroke incidence. The new index, ABSI, was significantly associated with total stroke incidence only in men (HR 1.54; 95% CI 1.06-2.23). CONCLUSIONS: Data from the Spanish EPIC cohort study show a strong association of WC and WHR with the relative risk of suffering a stroke only in men, while no associations were found for BMI. It supports the suggestion of other authors of using more than one obesity index in the study of stroke risk prediction.


Assuntos
Obesidade/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Adulto , Idoso , Índice de Massa Corporal , Ingestão de Energia , Grupo com Ancestrais do Continente Europeu , Feminino , Seguimentos , Humanos , Incidência , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Atividade Motora , Inquéritos Nutricionais , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Espanha , Circunferência da Cintura , Relação Cintura-Quadril
14.
Hum Mol Genet ; 24(5): 1432-40, 2015 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-25429063

RESUMO

Obesity and stroke are multifactorial diseases in which genetic, epigenetic and lifestyle factors are involved. The research aims were, first, the description of genes with differential epigenetic regulation obtained by an 'omics' approach in patients with ischemic stroke and, second, to determine the importance of some regions of these selected genes in biological processes depending on the body mass index. A case-control study using two populations was designed. The first population consisted of 24 volunteers according to stroke/non-stroke and normal weight/obesity conditions. The second population included 60 stroke patients and 55 controls classified by adiposity. DNA from the first population was analyzed with a methylation microarray, showing 80 cytosine-guanine dinucleotides (CpG) sites differentially methylated in stroke and 96 CpGs in obesity, whereas 59 CpGs showed interaction. After validating these data by MassArray Epityper, the promoter region of peptidase M20 domain containing 1 (PM20D1) gene was significantly hypermethylated in stroke patients. One CpG site at Caldesmon 1 (CALD1) gene showed an interaction between stroke and obesity. Two CpGs located in the genes Wilms' tumor 1 (WT1) and potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) were significantly hypermethylated in obese patients. In the second population, KCNQ1 was also hypermethylated in the obese subjects. Two CpGs of this gene were subsequently validated by methylation-sensitive high-resolution melting. Moreover, KCNQ1 methylation levels were associated with plasma KCNQ1 protein concentrations. In conclusion, obesity induced changes in the KCNQ1 methylation pattern which were also dependent on stroke. Furthermore, the epigenetic marks differentially methylated in the stroke patients were dependent on the previous obese state. These DNA methylation patterns could be used as future potential stroke biomarkers.


Assuntos
Metilação de DNA , Canal de Potássio KCNQ1/genética , Leucócitos/metabolismo , Obesidade/genética , Acidente Vascular Cerebral/genética , Idoso , Índice de Massa Corporal , Calmodulina/genética , Calmodulina/metabolismo , Proteínas de Ligação a Calmodulina/genética , Proteínas de Ligação a Calmodulina/metabolismo , Estudos de Casos e Controles , Ilhas de CpG , Epigênese Genética , Feminino , Marcadores Genéticos , Humanos , Canal de Potássio KCNQ1/sangue , Modelos Lineares , Masculino , Metaloproteases/genética , Metaloproteases/metabolismo , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Proteínas WT1/genética , Proteínas WT1/metabolismo
15.
Regul Pept ; 186: 1-6, 2013 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-23831408

RESUMO

Specific methylation of appetite-related genes in leukocytes could serve as a useful biomarker to predict weight regain after an energy restriction program. We aimed to evaluate whether the pre-intervention DNA methylation patterns involved in the epigenetic control of appetite-regulatory genes in leukocytes are associated with the weight regain process. Eighteen men who lost ≥5% of body weight after an 8-week nutritional intervention were categorized as "regainers" (≥10% weight regain) and "non-regainers" (<10% weight regain) 32weeks after stopping dieting. At baseline, leukocytes were isolated and DNA was analyzed for epigenetic methylation patterns of appetite-related gene promoters by MALDI-TOF mass spectrometry. Regainers showed higher methylation levels than non-regainers in proopiomelanocortin (POMC) CpG sites +136bp and +138bp (fold change from non-regainers=26%; p=0.020) and lower methylation of the whole analyzed region of neuropeptide Y (NPY; fold change from non-regainers=-22%; p=0.033), as well as of several individual NPY-promoter CpG sites. Importantly, total baseline NPY methylation was associated with weight-loss regain (r=-0.76; p<0.001), baseline plasma ghrelin levels (r=0.60; p=0.011) and leptin/ghrelin ratio (r=-0.52; p=0.046). Lower methylation levels of POMC CpG sites +136bp and +138bp were associated with success in weight-loss maintenance (odds ratio=0.042 [95% CI 0.01-0.57]; p=0.018), whereas lower total methylation levels in NPY promoter were associated with higher risk of weight regain (odds ratio=14.0 [95% CI 1.13-172]; p=0.039). Therefore, the study of leukocyte methylation levels reflects a putative epigenetic regulation of NPY and POMC, which might be implicated in the weight regain process and be used as biomarkers for predicting weight regain after dieting.


Assuntos
Leucócitos/metabolismo , Neuropeptídeo Y/genética , Obesidade/genética , Pró-Opiomelanocortina/genética , Regiões Promotoras Genéticas , Ganho de Peso/genética , Ilhas de CpG , Metilação de DNA , Grelina/sangue , Humanos , Leptina/sangue , Masculino , Neuropeptídeo Y/sangue , Obesidade/sangue , Obesidade/dietoterapia , Receptores para Leptina/genética
16.
Ren Fail ; 34(7): 885-91, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22583396

RESUMO

BACKGROUND: Methylmalonic aciduria is an inborn error of metabolism that causes renal failure and tubulointerstitial (TI) nephritis as complications. This study aimed to examine the levels of expression of several genes related to inflammation, oxidative stress, and mitochondrial function in the renal cortex of rats receiving methylmalonic acid (MMA). METHODS: Rats received MMA subcutaneously for a month. Tumor necrosis factor alpha (TNFα), nuclear factor-kappa B, interleukin 1 beta (IL-1ß), and cyclooxygenase 2 (COX-2) genes were examined by real-time polymerase chain reaction. We also examined transforming growth factor beta (TGF-ß) related to TI fibrosis, c-FOS, belonging to the immediate early gene family of transcription factors, and expression of SIRT1, related to energy production. RESULTS: There was significantly higher expression of TNFα and a trend toward a higher level of TGF-ß transcripts in the methylmalonic model group compared with the controls. However, SIRT1 expression was not different among the groups. Urinary MMA excretion correlated positively with mRNA level of TGF-ß. The expression of COX-2 was positively associated with the expression of c-FOS and inversely related to the expression of IL-1ß. CONCLUSIONS: The higher levels of TNFα and TGF-ß transcripts suggest inflammation and differentiation processes in the renal cortex in rats because of MMA. After 1 month of MMA injections, expression levels of SIRT1 were not affected, suggesting mitochondrial preservation in early stages of the disease.


Assuntos
Citocinas/metabolismo , Expressão Gênica/efeitos dos fármacos , Córtex Renal/efeitos dos fármacos , Ácido Metilmalônico/toxicidade , Animais , Ciclo-Oxigenase 2/metabolismo , Depuradores de Radicais Livres/farmacologia , Córtex Renal/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Pentoxifilina/farmacologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Wistar , Sirtuína 1/metabolismo
17.
Mult Scler ; 18(5): 569-77, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22127897

RESUMO

BACKGROUND: The association between multiple sclerosis (MS) and the HLA-DRB1*15:01 haplotype has been proven to be strong, but its molecular basis remains unclear. Vitamin D receptor (VDR) gene variants and sex have been proposed to modulate this association. OBJECTIVES: 1) Test the association of MS with *15:01 and VDR variants; 2) check whether VDR variants and/or sex modulate the risk conferred by *15:01; 3) study whether *15:01, VDR variants and/or sex affect HLA II gene expression. METHODS: Peripheral blood from 364 MS patients and 513 healthy controls was obtained and DNA and total RNA were extracted from leukocytes. HLA-DRB1, DRB5 and DQA1 gene expression measurements and *15:01 genotyping were performed by qPCR. VDR variants were genotyped by PCR-RFLP. RESULTS: Our data confirms that the *15:01 haplotype confers a higher risk of suffering from MS (OR = 1.364; 95% CI = 1.107-1.681). No association was found between VDR variants and MS, but they were shown to moderately modulate the risk conferred by *15:01. Sex confers a much stronger modulation and the *15:01-MS association seems to be female specific. A higher *15:01 frequency has been observed in Basques (45.1%). *15:01 positive samples showed a significant overexpression of DRB1 (p < 0.001), DRB5 (p < 0.001) and DQA1 (p = 0.004) in patients. DRB1 (p = 0.004) and DRB5 (p < 0.001) were also overexpressed in *15:01 controls. CONCLUSIONS: We confirm the *15:01-MS association and support that it is female specific. The relevance of ethnic origin on association studies has also been highlighted. HLA-DRB1*15:01 seems to be a haplotype consistently linked to high HLA II gene expression.


Assuntos
Variação Genética , Cadeias HLA-DRB1/genética , Esclerose Múltipla/genética , Adulto , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Regulação da Expressão Gênica , Frequência do Gene , Predisposição Genética para Doença , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/imunologia , Razão de Chances , Fenótipo , Reação em Cadeia da Polimerase , Receptores de Calcitriol/genética , Medição de Risco , Fatores de Risco , Fatores Sexuais , Espanha
18.
J. physiol. biochem ; 67(3): 463-470, sept. 2011.
Artigo em Inglês | IBECS | ID: ibc-122611

RESUMO

No disponible


Obesity-associated adipose tissue enlargement is characterized by an enhanced proinflammatory status and an elevated secretion of adipokines such as leptin and cytokines such as tumor necrosis factor (TNF)-alpha. Among the different mechanisms that could underlie the interindividual differences in obesity, epigenetic regulation of gene expression has emerged as a potentially important determinant. Therefore, 27 obese women (age, 32¨C50 years; baseline body mass index, 34.4 ¡À 4.2 kg/m2) were prescribed an 8-week low-calorie diet, and epigenetic marks were assessed. Baseline and endpoint anthropometric parameters were measured, and blood samples were drawn. Genomic DNA and RNA from adipose tissue biopsies were isolated before and after the dietary intervention. Leptin and TNF-alpha promoter methylation were measured by MSP after bisulfite treatment, and gene expression was also analyzed. Obese women with a successful weight loss (¡Ý5% of initial body weight, n = 21) improved the lipid profile and fat mass percentage (−12%, p < 0.05). Both systolic (−5%, p < 0.05) and diastolic (−8%, p < 0.01) blood pressures significantly decreased. At baseline, women with better response to the dietary intervention showed lower promoter methylation levels of leptin (−47%, p < 0.05) and TNF-alpha (−39%, p = 0.071) than the non-responder group (n = 6), while no differences were found between responder and non-responder group in leptin and TNF-alpha gene expression analysis. These data suggest that leptin and TNF-alpha methylation levels could be used as epigenetic biomarkers concerning the response to a low-calorie diet. Indeed, methylation profile could help to predict the susceptibility to weight loss as well as some comorbidities such as hypertension or type 2 diabetes (AU)


Assuntos
Humanos , Feminino , Leptina/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Metilação , Epigênese Genética/fisiologia , Obesidade/fisiopatologia , Dieta Redutora , Dieta com Restrição de Carboidratos , Hipertensão/prevenção & controle , Diabetes Mellitus Tipo 2/prevenção & controle , Suscetibilidade a Doenças
19.
Mov Disord ; 26(11): 2026-31, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21611983

RESUMO

It has been proposed that olfactory tests and metaiodobenzylguanidine cardiac scintigraphy may help diagnose idiopathic Parkinson's disease in the premotor phase. However, it is not clear what value these tests have in all patients with Parkinson's disease and, particularly, in those who carry mutations in LRRK2. The objective was to analyze olfactory dysfunction and the changes in cardiac I-metaiodobenzylguanidine uptake in patients with Parkinson's disease carrying the R1441G and G2019S mutations in LRRK2, and in patients with Parkinson's disease with no known mutations. Patients with Parkinson's disease were screened for R1441G and G2019S LRRK2 gene mutations and classified as LRRK2 mutation carriers or noncarriers. A total of 190 patients with Parkinson's disease (44 LRRK2 mutation carriers) were tested for olfactory dysfunction using the Brief Smell Identification Test. Cardiac (123) I-metaiodobenzylguanidine scintigraphy was performed on 90 patients with Parkinson's disease (27 LRRK2 mutation carriers). Thirty-six percent of patients with LRRK2 mutations have hyposmia, compared to 75% of noncarrier patients with Parkinson's disease (P < .001). Sixty-six percent of LRRK2 mutation carriers have low early metaiodobenzylguanidine uptake, compared to 86% of noncarriers (P = .048). Similarly, the heart/mediastinum ratio in delayed metaiodobenzylguanidine images appeared to differ between these groups of patients with Parkinson's disease, although these results did not reach statistical significance. The data obtained indicate that olfactory and cardiac impairment is less prevalent when Parkinson's disease is associated with mutations in LRRK2, although the underlying mechanisms for this difference remain unclear. Thus, such screening would be less useful to detect the premotor phase in asymptomatic relatives who carry mutations in LRRK2 than in cases not associated with LRRK2.


Assuntos
Predisposição Genética para Doença , Coração/diagnóstico por imagem , Mutação/genética , Transtornos do Olfato/etiologia , Doença de Parkinson , Proteínas Serina-Treonina Quinases/genética , 3-Iodobenzilguanidina , Idoso , Estudos de Coortes , Análise Mutacional de DNA , Feminino , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Masculino , Pessoa de Meia-Idade , Imagem de Perfusão do Miocárdio/métodos , Doença de Parkinson/complicações , Doença de Parkinson/genética , Doença de Parkinson/patologia , Compostos Radiofarmacêuticos , Paladar/genética , Paladar/fisiologia
20.
Diabetes Metab Res Rev ; 27(7): 705-16, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21591241

RESUMO

BACKGROUND: Dietary regimens providing different levels of protein and glycemic index (GI) foods when prescribed for weight management may also influence insulin sensitivity. PROCEDURES AND OUTCOMES: Overweight/obese adults in 8 European countries who lost ≥ 8% of initial body-weight (BW) after following a low calorie diet (LCD) were later randomly assigned with a 2x2 factorial design into 4 ad libitum dietary groups with two different protein content levels and dissimilar glycemic index, which were compared to a healthy reference diet. Specific markers assessing insulin resistance were measured. The LCD was initially applied to 932 adults and 773 were randomised to the 5 ad libitum diets. The 6-months programme was completed by 548 participants. The assignment to the Low Protein /High Glycemic Index diet induced a statistically higher HOMA-IR increase during the 6 months period as compared to the control. Contrariwise, the insulin response was lower in the High Protein/Low Glycemic Index diet after 60 and 90 min of an Oral Glucose Tolerance test subsequently carried out after the 6-months intervention. The Low Glycemic Index diets (either with high or low protein content) also lead to a decrease in fructosamine levels during the trial. CONCLUSION/INTERPRETATION: After a weight loss period, an increase in the dietary protein proportions and a decrease in the consumption of foods with a high Glycemic Index within an ad libitum dietary intervention aiming to weight maintenance produced favorable effects on glycaemic control and insulin sensitivity in overweight/obese subjects.


Assuntos
Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/prevenção & controle , Proteínas na Dieta , Índice Glicêmico , Sobrepeso/complicações , Adulto , Índice de Massa Corporal , Peso Corporal , Diabetes Mellitus Tipo 2/dietoterapia , Dieta , Feminino , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Sobrepeso/dietoterapia , Fatores de Risco
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