Seguimiento de las recomendaciones en prevención secundaria cerebrovascular en atención primaria / Compliance with recommendations in secondary prevention of stroke in primary care

OBJETIVO: Conocer el grado de seguimiento de las recomendaciones en prevención secundaria cerebrovascular en atención primaria e identificar factores asociados. DISEÑO: Transversal multicéntrico. Emplazamiento: Centros de salud de atención primaria de un área metropolitana (944.280 habitantes). PARTICIPANTES: Pacientes mayores de 18 años con diagnóstico de enfermedad cerebrovascular antes de 6 meses del estudio. Mediciones principales: Extracción de historia clínica informatizada de variables demográficas, factores de riesgo y comorbilidad cardiovascular, fármacos, valores de presión arterial (PA), colesterolLDL y visitas por medicina y enfermería posteriores al episodio. Se consideró buen control: PA < 140/90mmHg, colesterolLDL < 100mg/dl, abstención tabáquica y prescripción de fármacos preventivos (antiagregantes/anticoagulantes, estatinas e IECA/ARAII o diurético) en los últimos 18 meses. RESULTADOS: Un total de 21.976 sujetos, media de edad 73,1 años (DE: 12,1), 48% mujeres, el 72,7% con accidente vascular cerebral establecido. Comorbilidad: 70,8% HTA, 55,1% dislipidemia, 30,9% DM, 14,1% fibrilación auricular, 13,5% cardiopatía isquémica, 12,5% insuficiencia renal crónica, 8,8% insuficiencia cardiaca, 6,2% arteriopatía periférica, 7,8% demencia. Sin registro de: hábito tabáquico 3,7%, PA 3,5% y colesterolLDL 6,5%. Grado de control: 75,4% abstención tabáquica, 65,7% PA < 140/90 y 41,0% colesterolLDL< 100mg/dl. Tratamiento: 86,2% antiagregantes/anticoagulantes, 61,3% estatinas y 61,8% IECA/ARAII o diurético. El registro/grado de control fue superior en el grupo de 66-79 años e inferior en el de 18-40 años. CONCLUSIONES: El seguimiento de las recomendaciones de las guías clínicas para la prevención de la enfermedad cerebrovascular en atención primaria es mejorable, especialmente en los más jóvenes. Son necesarios cambios organizativos e intervención más activa de los profesionales, así como estrategias para combatir la inercia terapéutica

OBJECTIVE: Knowing compliance with secondary prevention recommendations of stroke in primary care and to identify factors associated with compliance. DESIGN: Multi-centre cross-sectional. SETTING: Health primary care centres in a metropolitan area (944,280 inhabitants). PARTICIPANTS: Patients aged 18 years and over with ischemic brain disease diagnosis prior to 6months before the study. MAIN MEASUREMENTS: Clinical history records of demographic variables, risk factors and cardiovascular comorbidity, drugs, blood pressure values (BP), LDL-cholesterol and medical visits by doctor and nurses after the event. Good adherence was considered when BP < 140/90 mmHg, LDL-cholesterol < 100 mg/dL, smoking abstention and preventive drugs prescription (anti-platelet/anticoagulants, statins and angiotensin-converting-enzyme inhibitors/angiotensin-receptor-antagonists or diuretics) during the last 18 months. RESULTS: A total of 21,976 patients, mean age 73.12 years (SD: 12.13), 48% women, 72.7% with stroke. Co-morbidity: hypertension 70.8%, dyslipidemia 55.1%, DM 30.9%, atrial fibrillation 14.1%, ischemic heart disease 13.5%, chronic renal failure 12.5%, heart failure 8.8%, peripheral arterial disease 6.2%, dementia 7.8%. No record was found for smoking in 3.7%, for BP in 3.5% and for LDL in 6.5%. Optimal control: abstention smoking in 3.7%, BP < 140/90 in 65.7% and LDL < 100 mg/dL in 41.0%. Treatment: 86.2% anti-platelet/anticoagulants, 61.3% statins and 61.8% angiotensin-converting-enzyme inhibitors, angiotensin-receptor-antagonists or diuretic. Registration and risk factors control was higher in 66-79 years aged and lower in 18-40 years aged. CONCLUSIONS: The implementation of clinical guidelines recommendations for stroke prevention in primary care must be improved, especially among younger population. Organizational changes and more active involvement by professionals and strategies against therapeutic inertia must be taken

[Compliance with recommendations in secondary prevention of stroke in primary care]. / Seguimiento de las recomendaciones en prevención secundaria cerebrovascular en atención primaria.

OBJECTIVE: Knowing compliance with secondary prevention recommendations of stroke in primary care and to identify factors associated with compliance. DESIGN: Multi-centre cross-sectional. SETTING: Health primary care centres in a metropolitan area (944,280 inhabitants). PARTICIPANTS: Patients aged 18years and over with ischemic brain disease diagnosis prior to 6months before the study. MAIN MEASUREMENTS: Clinical history records of demographic variables, risk factors and cardiovascular comorbidity, drugs, blood pressure values (BP), LDL-cholesterol and medical visits by doctor and nurses after the event. Good adherence was considered when BP <140/90 mmHg, LDL-cholesterol <100 mg/dL, smoking abstention and preventive drugs prescription (anti-platelet/anticoagulants, statins and angiotensin-converting-enzyme inhibitors/angiotensin-receptor-antagonists or diuretics) during the last 18months. RESULTS: A total of 21,976 patients, mean age 73.12 years (SD: 12.13), 48% women, 72.7% with stroke. Co-morbidity: hypertension 70.8%, dyslipidemia 55.1%, DM 30.9%, atrial fibrillation 14.1%, ischemic heart disease 13.5%, chronic renal failure 12.5%, heart failure 8.8%, peripheral arterial disease 6.2%, dementia 7.8%. No record was found for smoking in 3.7%, for BP in 3.5% and for LDL in 6.5%. Optimal control: abstention smoking in 3.7%, BP <140/90 in 65.7% and LDL <100 mg/dL in 41.0%. TREATMENT: 86.2% anti-platelet/anticoagulants, 61.3% statins and 61.8% angiotensin-converting-enzyme inhibitors, angiotensin-receptor-antagonists or diuretic. Registration and risk factors control was higher in 66-79years aged and lower in 18-40years aged. CONCLUSIONS: The implementation of clinical guidelines recommendations for stroke prevention in primary care must be improved, especially among younger population. Organizational changes and more active involvement by professionals and strategies against therapeutic inertia must be taken.

Demencia y género: una perspectiva desde la atención primaria / No disponible

Objetivo. Describir las características de las demencias en atención primaria (AP) en función del sexo de paciente y cuidador. Material y métodos. Estudio observacional transversal de 227 casos, con diagnóstico de demencia según criterios del CIE-10 (en cualquiera de sus variantes), en junio de 2009 en un centro de AP, recogiendo variables sociodemográficas, clínicas y asistenciales. Resultados. Encontramos edad mayor (83 frente a 78; p < 0,001) y escolarización menor en mujeres que en hombres (16,7 % de analfabetismo frente a 6,8 %). La enfermedad de Alzheimer fue el subtipo más frecuente, aunque con predominio mayor en mujeres (55,4 % frente a 39 %). La institucionalización (51,1 % frente a 32,2 %; p = 0,01), polifarmacia (7,6 frente a 6,1; p = 0,02) y uso de psicofármacos son mayores en mujeres, mientras que la frecuentación de AP y urgencias hospitalarias (UH) es inferior (p = 0,033). El cuidador más habitual es una mujer (64,8 %; p < 0,001). Los pacientes cuidados por hijas frecuentan menos las UH (p = 0,017) y reciben con mayor probabilidad tratamiento específico. Conclusiones. El perfil de las demencias en AP presenta diferencias entre hombres y mujeres. El paciente tipo sería una mujer, más añosa que en el caso de los hombres, menos escolarizada, con una demencia más evolucionada, más «medicalizada », más institucionalizada y menos frecuentadora. Las mujeres parecen generar menor sobrecarga asistencial directa, pero mayor impacto farmacológico y sociosanitario. El cuidador principal suele ser una mujer. Los pacientes cuidados por hijas frecuentan menos servicios hospitalarios y siguen con mayor probabilidad tratamiento específico(AU)

Objective. To describe the characteristics of dementia in primary care (AP) depending on the sex of patient and caregiver. Material and methods. Observational transversal study in a Primary Care (PC) center of 227 cases with diagnosis «dementia» ICD-10 (including all subtypes) in 2009, June, collecting socio-demographic, clinical and care-related variables. Results. We find women older (83 vs 78;p < 0.001) and with lower levels of schooling (16.7 % illiteracy vs 6.8 % men). Alzheimer’s disease was the most frequent diagnosis with higher prevalence in women (55,4 % vs 39 %). Institutionalization (51.1 % vs 32.2 %; p = 0.01), polypharmacy (7.6 vs 6.1; p = 0.02) and use of psychoactive drugs is higher in women, while PC and emergency units (EU) attendance is lower (p = 0,033). The most usual caregiver is a woman (64.8%; p < 0.001). Patients cared for by her daughters have less frequentation in EU (p = 0, 017) and follow most likely specific treatments. Conclusions. Dementia in PC presents valuable differences between men and women. The profile type would be a woman, most aged than men, with lower academic level, with a more evolved dementia, more exposed to drugs, more institutionalized and less frequenter. Women seem to generate less direct care overload, but greater pharmacological and social impact. Primary caregiver is usually a woman. Patients cared for his daughters present lower frequentation of hospital services and higher use of specific treatment(AU)

Mutational spectrum of semaphorin 3A and semaphorin 3D genes in Spanish Hirschsprung patients.

Hirschsprung disease (HSCR, OMIM 142623) is a developmental disorder characterized by the absence of ganglion cells along variable lengths of the distal gastrointestinal tract, which results in tonic contraction of the aganglionic colon segment and functional intestinal obstruction. The RET proto-oncogene is the major gene associated to HSCR with differential contributions of its rare and common, coding and noncoding mutations to the multifactorial nature of this pathology. In addition, many other genes have been described to be associated with this pathology, including the semaphorins class III genes SEMA3A (7p12.1) and SEMA3D (7q21.11) through SNP array analyses and by next-generation sequencing technologies. Semaphorins are guidance cues for developing neurons implicated in the axonal projections and in the determination of the migratory pathway for neural-crest derived neural precursors during enteric nervous system development. In addition, it has been described that increased SEMA3A expression may be a risk factor for HSCR through the upregulation of the gene in the aganglionic smooth muscle layer of the colon in HSCR patients. Here we present the results of a comprehensive analysis of SEMA3A and SEMA3D in a series of 200 Spanish HSCR patients by the mutational screening of its coding sequence, which has led to find a number of potentially deleterious variants. RET mutations have been also detected in some of those patients carrying SEMAs variants. We have evaluated the A131T-SEMA3A, S598G-SEMA3A and E198K-SEMA3D mutations using colon tissue sections of these patients by immunohistochemistry. All mutants presented increased protein expression in smooth muscle layer of ganglionic segments. Moreover, A131T-SEMA3A also maintained higher protein levels in the aganglionic muscle layers. These findings strongly suggest that these mutants have a pathogenic effect on the disease. Furthermore, because of their coexistence with RET mutations, our data substantiate the additive genetic model proposed for this rare disorder and further support the association of SEMAs genes with HSCR.

Cholecystokinin down-regulation by RNA interference impairs Ewing tumor growth.

PURPOSE: Tumors of the Ewing family are characterized by chromosomal translocations that yield chimeric transcription factors, such as EWS/FLI1, which regulate the expression of specific genes that contribute to the malignant phenotype. In the present study, we show that cholecystokinin (CCK) is a new target of the EWS/FLI1 oncoprotein and assess its functional role in Ewing tumor pathogenesis. EXPERIMENTAL DESIGN: Relevant EWS/FLI1 targets were identified using a combination of cell systems with inducible EWS/FLI1 expression, Ewing tumors and cell lines, microarrays, and RNA interference with doxycycline-inducible small hairpin RNA (shRNA) vectors. A doxycycline-inducible CCK-shRNA vector was stably transfected in A673 and SK-PN-DW Ewing cell lines to assess the role of CCK in cell proliferation and tumor growth. RESULTS: Microarray analysis revealed that CCK was up-regulated by EWS/FLI1 in HeLa cells. CCK was overexpressed in Ewing tumors as compared with other pediatric malignancies such as rhabdomyosarcoma and neuroblastoma, with levels close to those detected in normal tissues expressing the highest levels of CCK. Furthermore, EWS/FLI1 knockdown in A673 and SK-PN-DW Ewing cells using two different doxycycline-inducible EWS/FLI1-specific shRNA vectors down-regulated CCK mRNA expression and diminished the levels of secreted CCK, showing that CCK is a EWS/FLI1 specific target gene in Ewing cells. A doxycycline-inducible CCK-specific shRNA vector successfully down-regulated CCK expression, reduced the levels of secreted CCK in Ewing cell lines, and inhibited cell growth and proliferation in vitro and in vivo. Finally, we show that Ewing cell lines and tumors express CCK receptors and that the growth inhibition produced by CCK silencing can be rescued by culturing the cells with medium containing CCK. CONCLUSIONS: Our data support the hypothesis that CCK acts as an autocrine growth factor stimulating the proliferation of Ewing cells and suggest that therapies targeting CCK could be promising in the treatment of Ewing tumors.

Expression of hpttg proto-oncogene in lymphoid neoplasias.

Pituitary tumor-transforming gene (pttg) is a distinct proto-oncogene which is expressed in certain normal tissues with high proliferation rate and in a variety of tumors. PTTG is the vertebrate analog of yeast securins Pds1 and Cut2 with a key role in the regulation of sister chromatid separation during mitosis. Impairment of PTTG regulated functions is expected to lead to chromosomal instability and aneuploidy. Human pttg (hpttg) is abundantly expressed in Jurkat T lymphoblastic lymphoma cells but not in normal peripheral blood leukocytes. To obtain additional data on the potential role of hpttg in lymphomagenesis we selected 150 cases of lymphoid tumors for the assessment of hpttg expression in tumor tissues. Immunohistochemical studies on formalin-fixed, paraffin-embedded tissues revealed hPTTG in 38.8% of B-cell lymphomas, 70.2% of T-cell lymphomas, and 73.1% of Hodgkin's lymphomas. Among B-cell lymphomas, the most frequently immunostained tumors were plasma cell tumors, diffuse large cell lymphomas, and follicle center cell lymphomas. In Hodgkin's disease, immunoreactivity was mainly noted in Reed-Sternberg cells. In conclusion, the frequent overexpression of hpttg in many histological subtypes of lymphoma suggests the involvement of this proto-oncogene in lymphomagenesis.

Glial-derived neurotropic factor and RET gene expression in normal human anterior pituitary cell types and in pituitary tumors.

Glial-derived neurotropic factor (GDNF) signaling is mediated through a 2-component system consisting of the so-called GDNF receptor-alpha (GFRalpha1), which binds to GDNF. This complex activates the tyrosine kinase receptor RET. In this paper we demonstrate GDNF, GFRalpha1, and RET mRNA and protein expression in the human anterior pituitary gland. Double immunohistochemistry of anterior pituitary sections showed GDNF immunoreactivity in more than 95% of somatotrophs and to a lesser extent in corticotrophs (20%); it was almost absent in the remaining cell types. Also, although more than 95% of somatotrophs were stained for RET, no positive immunostaining could be detected in other cell types. Furthermore, we have looked for GDNF and RET in human pituitary adenomas of various hormonal phenotypes. Strong positive immunostaining was found for c-RET in all of the GH-secreting adenomas screened as well as in 50% of ACTH-producing adenomas. Positive immunostaining for GDNF was found in all of the GH-secreting adenomas and in 10% of the corticotropinomas. Lastly, we found strong positive immunostaining for GFRalpha1 in 90% of the somatotropinomas and 50% of the corticotropinomas as well as in 1 of 8 prolactinomas and 1 of 13 nonfunctioning adenomas. All of the remaining pituitary tumors screened were negative for RET, GDNF, and GFRalpha1. This study indicates that GDNF may well be acting in the regulation of somatotroph cell growth and/or cell function in the normal human anterior pituitary gland. The expression of RET in all of the somatotropinomas and in 50% of the ACTH-producing tumors implies that GDNF and RET could be involved in the pathogenesis of pituitary tumors.