José Luis Martín de Pablos

Efficacy of a home blood pressure monitoring programme on therapeutic compliance in hypertension: the EAPACUM- HTA study

Objective To evaluate the efficacy of a programme of home blood pressure measurement (HBPM) on therapeutic compliance in mild-to-moderate hypertension. Design A prospective controlled multicentre clinical trial. Setting Forty primary care centres in Spain, with a duration of 6 months. Patients A total of 250 patients with newly diagnosed or uncontrolled hypertension were included. Interventions The patients were randomly selected and distributed in two groups: (1) the control group (CG) who received standard health intervention; (2) the intervention group (IG): the patients in this group received an OMRON in their homes for a programme of HBPM. Main outcome measure Four visits were scheduled, for the measurement of blood pressure (BP). They were provided with an electronic monitor for measuring compliance (monitoring events medication system; MEMS). Therapeutic compliance was defined as a drug consumption of 80–110%. A number of variables were calculated using the MEMS. The mean BP were calculated and the percentage of controlled patients. Results A total of 200 patients completed the study (100 in each group). Compliance was observed in 74 and 92%, respectively, in the CG and IG [95% confidence interval (CI) 63.9–84.1 and 86.7–97.3; P = 0.0001], the mean percentage compliances were 87.6 and 93.5% (95% CI 81.2–94 and 80.7–98.3; P = 0.0001), the percentages of correct days were 83.6 and 89.4%, the percentages of subjects who took the medication at the prescribed time were 79.89 and 88.06%, and the levels of therapeutic cover were 86.7 and 93.1%. The number needed to treat to avoid one case of non-compliance was 5.6 patients. The differences in the mean decreases in BP were significant for diastolic BP, with a greater decrease observed in the IG. Conclusions An HBPM programme using electronic monitors is effective in improving compliance in arterial hypertension, measured using the MEMS.

T Cell Migration in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation in joints, associated with synovial hyperplasia and with bone and cartilage destruction. Although the primacy of T cell-related events early in the disease continues to be debated, there is strong evidence that autoantigen recognition by specific T cells is crucial to the pathophysiology of rheumatoid synovitis. In addition, T cells are key components of the immune cell infiltrate detected in the joints of RA patients. Initial analysis of the cytokines released into the synovial membrane showed an imbalance, with a predominance of proinflammatory mediators, indicating a deleterious effect of Th1 T cells. There is nonetheless evidence that Th17 cells also play an important role in RA. T cells migrate from the bloodstream to the synovial tissue via their interactions with the endothelial cells that line synovial postcapillary venules. At this stage, selectins, integrins, and chemokines have a central role in blood cell invasion of synovial tissue, and therefore in the intensity of the inflammatory response. In this review, we will focus on the mechanisms involved in T cell attraction to the joint, the proteins involved in their extravasation from blood vessels, and the signaling pathways activated. Knowledge of these processes will lead to a better understanding of the mechanism by which the systemic immune response causes local joint disorders and will help to provide a molecular basis for therapeutic strategies.

Análisis de los estudios publicados sobre el incumplimiento terapéutico en el tratamiento de la hipertensión arterial en España entre los años 1984 y 2005

Objetivos Analizar el incumplimiento farmacologico de la hipertension arterial (HTA) en Espana, a partir de una revision de estudios publicados entre 1984 y 2005. Diseno Revision sistematica. Fuentes de datos Se realizo una busqueda mediante internet (Medline e indice espanol de tesis doctorales), busqueda manual de diferentes revistas espanolas y referencias bibliograficas de articulos detectados sobre cumplimiento y contacto personalizado de expertos. Los descriptores fueron: hypertension and patient compliance, or compliance, or adherence, or patient dropouts or treatment refusal y sus combinaciones. Seleccion de estudios Se incluyen estudios publicados entre 1984-2005, como articulos originales, resumenes de congresos o tesis doctorales, realizados en Espana y que utilizaran como metodo de medida el recuento de comprimidos o el de aberturas de los monitores electronicos (MEMS) y haber definido a los incumplidores, con un porcentaje de cumplimiento 110%. Extraccion de datos Se calcularon el porcentaje de incumplidores y sus intervalos de confianza (IC) del 95%, y la media ponderada del porcentaje de incumplidores de cada estudio. Resultados Se ha obtenido un total de 26 estudios de investigacion publicados en Espana, excluyendose 2 del analisis. El numero total de pacientes incluidos ha sido de 3.553 hipertensos, con un 32,53% de incumplidores (n = 1.156; IC del 95%, 29,83-35,23) y un 67,47% de cumplidores (n = 2.397; IC del 95%, 65,67-69,27). La media ponderada del porcentaje de incumplimiento fue del 32,78%. Conclusiones El porcentaje de incumplimiento en el tratamiento farmacologico de la HTA en Espana ha descendido en los ultimos anos, aunque sigue siendo elevado.

El control de la inercia terapéutica en el tratamiento de la hipertensión arterial mediante diferentes estrategias

OBJECTIVE To evaluate the efficacy of different interventions on therapeutic Inertia (TI) in mild-to-moderate hypertension (AHT). DESIGN Controlled, randomised clinical trial. SETTING Two hundred clinics in 5 primary care centres. Spain. PARTICIPANTS A total of 1104 patients with uncontrolled hypertension were included. INTERVENTION Four groups with 276 patients were formed: 1) Control group (CG): standard health intervention; 2) Education intervention and a program of home blood pressure monitoring (HBPM) (EG); 3) Card control intervention and HBPM programme (CHG); 4) Education intervention, card control and HBPM programme (ECHG). MAIN MEASUREMENTS TI was calculated by the rate: (Number of patients whose pharmacological treatment was not changed in each visit/Number of patients with an average BP 140mmHg and/or 90mmHg in the general population or 130 and/or 90 mmHg in diabetics). The mean BPs and the percentage of controlled patients were calculated. The mean number of people that required an intervention in order to avoid TI was calculated (NI). RESULTS A total of 921 patients completed the study, and 1842 visits were made, with TI in 36.8% (IC=5.8%) of the sample and in 82.58% (IC=8.2%) of the uncontrolled hypertensive patients. The TI was 60% (CI=4.2%), 38.4% (CI=4.4%) 30.2 (CI=4.3%) and 14.7 (CI=3.3%) (p=0.001) for CG, EG, CHG and ECHG, respectively. The percentage controlled at the end of study was 35.3% (CI=1.1%), 54.7% (CI=1.8%), 60.2% (CI=2.1%) and 65.1% (CI=2.2%) (p<0.01) for CG, EG, CHG and ECHG, respectively. The NI were 4.6, 3.3 and 2.2 for CG, EG, CHG and ECHG, respectively. CONCLUSIONS TI was very significant among the uncontrolled hypertensive patients. The studied interventions are effective for improving TI.

Intervención no farmacológica como estrategia para favorecer el control de la hipertensión arterial y mejorar el cumplimiento antihipertensivo

OBJECTIVE To evaluate the efficacy of an intervention by means of an educational magazine on treatment compliance in uncontrolled arterial hypertension (AHT). DESIGN Controlled, randomised clinical trial. SETTING 87 primary care centres. Spain. PARTICIPANTS A total of 450 patients with uncontrolled hypertension were included. INTERVENTION Two groups of 225 patients were formed: 1) Control group (CG): standard health intervention; 2) Intervention Group (IG): received a twice monthly educational magazine at home. MAIN MEASUREMENTS Compliance was measured using the Medication Event Monitoring System (MEMS-Aardex). Compliance rate (CR) was recorded. Compliers were defined as individuals with a treatment compliance of 80-110%. The percentage of compliers, the mean percentage of doses taken and the percentage of patients taking the medication at the correct times were estimated. The mean blood pressures (BPs) and the percentage of controlled patientswere calculated. The number needed to treat (NNT) was calculated. RESULTS A total of 393 individuals were evaluable (Age: 62.4 years), 196 in the IG and 197 in the CG. There were 83.2% (95% CI 78-88.4) and 49.2% (95% CI 42.2-56.2) (P=0.0001) of overall compliers in the IG and CG, respectively and 74% (95% CI: 67.9-80.1) and 42.6% (95% CI=35.7-49.5) (P=0.0001) of correct times compliers. A total of 81.6% (95% CI=76.2-86.5%)) were controlled in the IG and 56.3% (95% CI=49.4-63.2) in the CG. The NNT was 3.3 patients. CONCLUSIONS Therapeutic non-compliance was very high. The educational magazine is an effective strategy to improve the compliance and degree of control of the AHT.

CXCL12 Regulates through JAK1 and JAK2 Formation of Productive Immunological Synapses.

The adaptive immune response requires interaction between T cells and APC to form a specialized structure termed the immune synapse (IS). Although the TCR is essential for IS organization, other factors such as chemokines participate in this process. In this study, we show that the chemokine CXCL12-mediated signaling contributes to correct IS organization and therefore influences T cell activation. CXCR4 downregulation or blockade on T cells caused defective actin polymerization at the contact site with APC, altered microtubule-organizing center polarization and the IS structure, and reduced T cell/APC contact duration. T cell activation was thus inhibited, as shown by reduced expression of CD25 and CD69 markers and of IL-2 mRNA levels. The results indicate that, through Gi and JAK1 and 2 kinases activation, CXCL12 signaling cooperates to build the IS and to maintain adhesive contacts between APC and T cells, required for continuous TCR signaling.

¿Los pacientes con alto riesgo vascular toman correctamente la medicación antihipertensiva? Estudio Cumple-MEMS

INTRODUCTION AND OBJECTIVES To assess compliance with treatment inhibit the renin-angiotensin system (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) in uncontrolled hypertension in patients at high cardiovascular risk. METHODS Prospective, longitudinal, multicenter study, carried out in 102 Spanish primary care centers. We included 808 uncontrolled hypertensive patients treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers who were at high vascular risk; 4 visits were conducted: baseline and 1, 3, and 6 months later. Compliance was measured by electronic monitors. We calculated the mean percentage compliance, the overall percentage of compliers, once-daily compliers, compliers with the prescribed time frame, and antihypertensive coverage. We considered a patient to be a complier when the percentage compliance was 80%-100%. RESULTS In all, 701 patients completed the study (mean age, 63.7 [11.1] years). The systolic and diastolic blood pressures decreased significantly (P<.0001) to 18.8 mmHg and 9.8 mmHg, respectively. The control rate was 70% (95% confidence interval, 65.6%-74.4%) (P=.0001). The rate of control was significantly higher among compliers than noncompliers (P<.05). The mean percentage of doses taken was 87.9% (95% confidence interval, 84.8%-91%) and the mean therapeutic coverage was 82.4% (95% confidence interval, 78.7%-86.1%). Overall, 73.3% of the patients were compliers (95% confidence interval, 69%-77.6%), 52.8% (95% confidence interval, 48%-57.6%) were once-daily compliers, and 46.5% (95% confidence interval, 41.9%-51.1%) complied with the prescribed time frame. Noncompliance was associated with a higher number of drugs prescribed (P<.001). CONCLUSIONS In hypertensive patients at high vascular risk, the rate of therapeutic noncompliance was very high, mainly when they took 5 or more pills daily.

El cumplimiento terapéutico en las dislipemias medido mediante monitores electrónicos. ¿Es eficaz un calendario recordatorio para evitar los olvidos?☆☆☆

Objetivo. Analizar la eficacia de la intervencion mediante un calendario recordatorio de la toma de medicacion en el cumplimiento terapeutico de las dislipemias. Diseno. Ensayo clinico controlado, aleatorizado. Emplazamiento. Doce consultas de 5 centros de atencion primaria. Participantes. Se selecciono a 220 pacientes con hipercolesterolemia diagnosticados segun criterios del National Cholesterol Education Program (NCEP). Intervencion. Se formaron 2 grupos: a) grupo control (GC), con 110 pacientes, que recibieron la intervencion habitual, y b) grupo intervencion (GI), con 110 pacientes que recibieron ademas un calendario recordatorio de la toma de medicacion. Mediciones principales. Se estudio el cumplimiento mediante monitores electronicos de control de medicacion (MEMS) y se determino el colesterol, los trigliceridos, el colesterol de las lipoproteinas de alta densidad (cHDL) y el de las de baja densidad (cLDL) al inicio, al tercero y al sexto mes. Se compararon los porcentajes de cumplidores (80-110%), el porcentaje medio de cumplimiento y el grado de control. Se calculo la reduccion del riesgo absoluto (RRA) y el relativo (RRR) y el numero de individuos que se necesita tratar para evitar un incumplimiento (NNT). Resultados. Finalizaron 188 sujetos (el 85,45% de la muestra); el GI lo componian 96 individuos, y el GC, 92. Hubo un 26,55% (intervalo de confianza [IC], ±6,3%) de incumplidores, el 10,5% (IC, ±6,1%) en el GI y el 42,6% (IC, ±10,1%) en el GC (p < 0,001). La media del porcentaje de cumplimiento fue del 88,1% (IC, ±4,6%), el 92% (IC, ±5,4%) en el GI y el 84% (IC, ±7,4%) en el GC (p < 0,05). Se observaron descensos significativos en el GI para el colesterol total y el cLDL. El porcentaje de pacientes con colesterol controlado fue del 66,7% (IC, ±9,4%) en el GI y el 41,2% (IC, ±10%) en el GC (p < 0,01), y el cLDL en el 41,2% del GI y el 35,8% en el GC (p = NS). La RRA fue del 32,1%, la RRR del 75,35% y el NNT de 3,1 pacientes. Conclusiones. La intervencion con un calendario recordatorio es una medida eficaz para mejorar el porcentaje de cumplidores en el tratamiento de las dislipemias.

El cumplimiento terapéutico con insulina en el tratamiento de la diabetes mellitus tipo 2: estudio CUMINDIAB

OBJECTIVE To determine the percentage of therapeutic noncompliance among type 2 diabetes patients on treatment with insulin. DESIGN Prospective multicentre study. SETTING Nine Primary Care Health Centre in Huelva (Spain). PARTICIPANTS A total of 121 type 2 diabetics, who, in the opinion of their doctor, need to start treatment with insulin or have their insulin treatment modified. MAIN MEASUREMENTS Five visits were made (enrolment, 6, 12, 18 and 24 months). The variables analysed were, fasting blood glucose, glycosylated haemoglobin, compliance with insulin treatment, measured by counting insulin units. The percentage compliance (PC) was calculated by (PC = Total No. of insulin units expected to be consumed / Total No. of insulin units that should have been taken x 100). A complier was considered as one who achieved a PC between 80 and 100%. RESULTS There were 103 evaluable subjects (85.8%) with a mean age of 66.4 (SD 11.6) years, and 45 were male (42.8%). The mean percentage compliance with insulin was 90.9% (95% CI, 84.2-97.6%). At the 6, 12, 18 and 24 months visits it was 92.1% (95% CI, 85.6-98.6%), 92.3, 90.1 and 89.2% (95% CI, 81.7-96.7%), respectively. Overall patient compliance was 74.75% (95% CI, 64.3-85.2%). For the visits, compliance was 82.5% (95% CI, 73.3-91.7%), 77.7%, 73.8% and 71.8% (95% CI, 60.9-82.7%), respectively (P<.05 initial-final). CONCLUSIONS A quarter of the diabetic patients did not comply with their insulin treatment.

Non-compliance and inertia in hypertensive Spaniards at high cardiovascular risk: CUMPLE study

Abstract Objective: To assess non-compliance (NC) and therapeutic inertia (TI) after 6 months of follow-up in hypertensive patients with poorly controlled blood pressure and high cardiovascular risk. Research design and methods: Longitudinal, multicentre study; 3900 uncontrolled hypertensive patients were recruited from 585 primary healthcare centres. Tablets were counted during visits at baseline, 1, 3 and 6 months. A tablet count between 80–100% was considered as compliant. Multivariate logistic regression was performed to determine variables associated with NC and TI. Results: A total of 3636 patients completed, mean age was 64.8 (SD 10.8) years, 53.7% being male. After one month, 61.8% (60.2–63.4) had uncontrolled blood pressure, 39.5% (37.9–41.1) were NC and 52.3% (50.2–54.4) had TI. At the end of follow-up, uncontrolled blood pressure was 34.6% (33.1–36.1) (p < 0.05), NC was 46.8% (45.2–48.4) (p < 0.05) and TI was 34.2% (31.6–36.8) (p < 0.05). The variable associated with NC was greatest number of antihypertensive treatments (OR 1.09, 95% CI 1.05–1.13, p < 0.001), and variables associated with TI were least number of antihypertensive drugs (OR 0.88, 95% CI 0.84–0.98, p < 0.001) and least number of diseases suffered (OR 0.95, 95% CI 0.92–0.98, p = 0.002). Limitations: Due to the complexity of measuring compliance, we have to assume measurement bias. Conclusions: Among uncontrolled hypertensive patients, after completing 6 months follow-up, approximately one out of two patients were NC and one out of three physicians committed TI.