Single nucleotide polymorphisms in ADAM17, IL23R and SLCO1C1 genes protect against infliximab failure in adults with Crohn's disease.

BACKGROUND: To predict primary failure of infliximab (IFX) therapy in Crohn's disease (CD) and to identify patients who maintain long-term effectiveness to IFX is currently not feasible. Some genetic variations are proposed as potential biomarkers. AIM: We assessed a set of single nucleotide polymorphisms (SNPs) in genes related to the IFX mechanism of action and the presence of HLA-DQA1 * 05 allele on the primary response and long-term durability in CD patients. METHODS: A multi-centre cross-sectional study of IFX-exposed adult patients with CD was undertaken. Treatment persistence and time to failure were co-primary endpoints. DNA from the 131 patients was genotyped. Association between SNPs and clinical variables with IFX persistence was assessed. RESULTS: Failure to IFX was documented in 65 (49.6%) out of 131 patients. IFX persistence was associated either with carrying the TT genotype in ADAM17 rs10929587 (ORa=0.2; 95%CI=0.1-0.8; p = 0.021), or the CC genotype in SLCO1C1 rs3794271 (ORa=0.2; 95%CI=0.1-0.7; p = 0.008), according to multivariate logistic regression. In contrast, previous bowel resection increased the risk of IFX failure (ORa=2.8; 95%CI=1.1-7.3; p = 0.025). Cox regression analysis confirmed these findings and also identified IL23R rs10489629-TT (HRa 0.41; 95%CI=0.22-0.75; p = 0.004) and concomitant immunosuppressants (HRa 0.46; 95%CI=0.27-0.77; p = 0.003) as protection from IFX failure. However, no association between HLA-DQA1 * 05 allele and persistence of IFX therapy was found, with similar failure rates among carriers and non-carriers (52.8% vs. 47.4%, respectively; p = 0.544). CONCLUSIONS: SNPs rs10929587-TT in ADAM17, rs10489629-TT in IL23R and rs3794271-CC in SLCO1C1, together with no previous bowel surgery and concomitant immunosuppression, were identified as protection from failure to IFX.

Consensus of experts from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology for the genotyping of DPYD in cancer patients who are candidates for treatment with fluoropyrimidines.

5-Fluorouracil (5-FU) and oral fluoropyrimidines, such as capecitabine, are widely used in the treatment of cancer, especially gastrointestinal tumors and breast cancer, but their administration can produce serious and even lethal toxicity. This toxicity is often related to the partial or complete deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme, which causes a reduction in clearance and a longer half-life of 5-FU. It is advisable to determine if a DPD deficiency exists before administering these drugs by genotyping DPYD gene polymorphisms. The objective of this consensus of experts, in which representatives from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology participated, is to establish clear recommendations for the implementation of genotype and/or phenotype testing for DPD deficiency in patients who are candidates to receive fluoropyrimidines. The genotyping of DPYD previous to treatment classifies individuals as normal, intermediate, or poor metabolizers. Normal metabolizers do not require changes in the initial dose, intermediate metabolizers should start treatment with fluoropyrimidines at doses reduced to 50%, and poor metabolizers are contraindicated for fluoropyrimidines.

Genes differentially expressed by methylprednisolone in vivo in CD4 T lymphocytes from multiple sclerosis patients: potential biomarkers.

Intravenous methylprednisolone (IVMP) is the gold standard treatment in acute relapses of multiple sclerosis. Knowing the response to IVMP in advance could facilitate earlier selection of patients for subsequent courses of therapy. However, molecular mechanisms and changes in gene expression induced by methylprednisolone remain unknown. The aim of the study was to identify in vivo differentially expressed genes in relapsing-remitting multiple sclerosis patients after 3-6 days of treatment with IVMP. For this purpose, whole-genome transcription profiling of CD4+ T lymphocytes was performed before and after treatment with IVMP in 8 relapsing-remitting multiple sclerosis patients during relapse using Human GE 4x44K v2 microarrays. Differentially expressed genes were identified using a paired t test on GeneSpring v13.0 software. A P-value <0.001 and a twofold change were considered significant. Microarray data were confirmed using real-time PCR. Microarray revealed changes in gene expression: four genes were downregulated (B3GNT3, ZNF683, IFNG and TNF) and seven upregulated (DEFA4, CTSG, DEFA8P, AZU1, MPO, ELANE and PRTN3). Pathway analysis revealed the transforming growth factor-ß signaling pathway to be affected. Comparison with previously published data on in vitro methylprednisolone-regulated genes showed that SMAD7, TNF and CHI3L1 were also downregulated in vivo in relapsing-remitting multiple sclerosis patients. In summary, we performed the first in vivo transcriptome analysis in CD4+ T lymphocytes before and after the treatment with IVMP in patients with multiple sclerosis. Identification of differentially expressed genes in patients receiving IVMP could improve our understanding of the molecular mechanisms underlying the therapeutic effects of IVMP and highlight potential biomarkers of the response to IVMP.

[Validation of genetic polymorphisms associated to the toxicity of chemotherapy in colorectal cancer patients]. / Validación de polimorfismos genéticos asociados a toxicidad al tratamiento quimioterápico en pacientes de cáncer colorrectal.

OBJECTIVE: To validate the associations previously found in three cohorts of patients from the General University Hospital Gregorio Marañón, between the polymorphisms rs1128503, rs2032582 and rs1045642 of the ABCB1 gene and the hand-foot syndrome and diarrhea in colorectal cancer patients treated with chemotherapy regimes containing Capecitabine and 5-Fluorouracil, respectively, and between the polymorphisms rs2297595 of the DPYD gene and nausea/vomiting, rs11615 of ERCC1 and neutropenia, and rs28399433 CYP2A6 and neutropenia, in colorectal cancer patients treated with FOLFOX or XELOX as adjuvant therapy. METHOD: Colorectal cancer patients treated with chemotherapy regimes, containing Capecitabine (n = 157), 5-Fluorouracil (n = 99) were included in the study, as well as patients treated with XELOX or FOLFOX (n = 83) as adjuvant therapy. The patients included were recruited from the Doce de Octubre University Hospital and from the Gregorio Marañón General University Hospital, and signed the informed consent form. DNA was obtained from blood samples. Genotyping was carried out with SNaPshot. Contingency tables were created for analyzing the associations between the genotypes and the adverse reactions. RESULTS: None of the associations previously identified was replicated in the validation cohort. CONCLUSIONS: Pharmacogenetic studies with a limited sample size must be validated with bigger cohorts, if possible by means of multicentre studies, reducing the variables to the maximum and should never be used in clinical practice without validation.

OBJETIVO: Validar las asociaciones, encontradas previamente en tres cohortes de pacientes del Hospital General Universitario Gregorio Marañón, entre los polimorfismos rs1128503, rs2032582 y rs1045642 del gen ABCB1 con síndrome manopie y diarrea en pacientes de cáncer colorrectal tratados con regímenes que contenían capecitabina y 5-Fluorouracilo, respectivamente, y entre los polimorfismos rs2297595 del gen DPYD con nauseas/vómitos, rs11615 ERCC1 y neutropenia, y rs28399433 CYP2A6 y neutropenia en pacientes de cáncer colorrectal tratados con FOLFOX o XELOX en adyuvancia. MÉTODO: Se incorporaron al estudio pacientes de cáncer colorrectal tratados con regímenes quimioterápicos que contenían capecitabina (n = 157), 5-fluorouracilo (n = 99) y pacientes tratados en adyuvancia con XELOX o FOLFOX (n = 83). Los pacientes participantes fueron reclutados en el Hospital Universitario Doce de Octubre y en el Hospital General Universitario Gregorio Marañón tras firmar consentimiento informado. Se extrajo ADN a partir de muestras de sangre. Los genotipados se realizaron mediante SNaPshot. Se realizaron tablas de contingencia para analizar las asociaciones entre genotipos y reacciones adversas. RESULTADOS: Ninguna de las asociaciones previamente identificadas fue replicada en la cohorte de validación. CONCLUSIONES: Los estudios farmacogenéticos con un tamaño muestral limitado deben ser validados en cohortes más numerosas, a ser posible en estudios multicéntricos, reduciendo al máximo las variables y nunca deben ser utilizados en clínica sin validar.

A genome-wide association study on copy-number variation identifies a 11q11 loss as a candidate susceptibility variant for colorectal cancer.

Colorectal cancer (CRC) is a complex disease, and therefore its development is determined by the combination of both environmental factors and genetic variants. Although genome-wide association studies (GWAS) of SNP variation have conveniently identified 20 genetic variants so far, a significant proportion of the observed heritability is yet to be explained. Common copy-number variants (CNVs) are one of the most important genomic sources of variability, and hence a potential source to explain part of this missing genetic fraction. Therefore, we have performed a GWAS on CNVs to explore the relationship between common structural variation and CRC development. Phase 1 of the GWAS consisted of 881 cases and 667 controls from a Spanish cohort. Copy-number status was validated by quantitative PCR for each of those common CNVs potentially associated with CRC in phase I. Subsequently, SNPs were chosen as proxies for the validated CNVs for phase II replication (1,342 Spanish cases and 1,874 Spanish controls). Four common CNVs were found to be associated with CRC and were further replicated in Phase II. Finally, we found that SNP rs1944682, tagging a 11q11 CNV, was nominally associated with CRC susceptibility (p value = 0.039; OR = 1.122). This locus has been previously related to extreme obesity phenotypes, which could suggest a relationship between body weight and CRC susceptibility.

Estradiol downregulates NF-κb translocation by Ikbkg transcriptional repression in dendritic cells.

To reconcile immunity and reproduction, females must allow spermatozoa to survive and control the presence of commensal microbiota and sexually transmitted pathogens during ovulation. Female steroid sex hormones exert a powerful effect on the immune system, as do the hormonal changes associated with the ovarian cycle. Dendritic cells (DCs) are immunological sentinels that link innate immunity to adaptive immunity. Upon exposure to microbial invaders in tissue, they undergo a maturational process that culminates in the lymph nodes and activates T-cell-specific immune responses. Estradiol, which is highly expressed during ovulation, has an effect on the maturation of DCs, although the molecular mechanism remains elusive. We detected that estradiol regulates expression of Ikbkg in DCs and modulates nuclear factor-κb translocation to the nucleus, thus explaining the reduced DC function observed during ovulation. This change may be an adaptive mechanism to reconcile control of infection and reproductive functions.

BMP2/BMP4 colorectal cancer susceptibility loci in northern and southern European populations.

Genome-wide association studies have successfully identified 20 colorectal cancer susceptibility loci. Amongst these, four of the signals are defined by tagging single nucleotide polymorphisms (SNPs) on regions 14q22.2 (rs4444235 and rs1957636) and 20p12.3 (rs961253 and rs4813802). These markers are located close to two of the genes involved in bone morphogenetic protein (BMP) signaling (BMP4 and BMP2, respectively). By investigating these four SNPs in an initial cohort of Spanish origin, we found substantial evidence that minor allele frequencies (MAFs) may be different in northern and southern European populations. Therefore, we genotyped three additional southern European cohorts comprising a total of 2028 cases and 4273 controls. The meta-analysis results show that only one of the association signals (rs961253) is effectively replicated in the southern European populations, despite adequate power to detect all four. The other three SNPs (rs4444235, rs1957636 and rs4813802) presented discordant results in MAFs and linkage disequilibrium patterns between northern and southern European cohorts. We hypothesize that this lack of replication could be the result of differential tagging of the functional variant in both sets of populations. Were this true, it would have complex consequences in both our ability to understand the nature of the real causative variants, as well as for further study designs.

Pharmacogenomics in colorectal cancer: a genome-wide association study to predict toxicity after 5-fluorouracil or FOLFOX administration.

The development of genotyping technologies has allowed for wider screening for inherited causes of variable outcomes following drug administration. We have performed a genome-wide association study (GWAS) on 221 colorectal cancer (CRC) patients that had been treated with 5-fluorouracil (5-FU), either alone or in combination with oxaliplatin (FOLFOX). A validation set of 791 patients was also studied. Seven SNPs (rs16857540, rs2465403, rs10876844, rs10784749, rs17626122, rs7325568 and rs4243761) showed evidence of association (pooled P-values 0.020, 9.426E-03, 0.010, 0.017, 0.042, 2.302E-04, 2.803E-03) with adverse drug reactions (ADRs). This is the first study to explore the genetic basis of inter-individual variation in toxicity responses to the administration of 5-FU or FOLFOX in CRC patients on a genome-wide scale.

Effect of ammonia on ciliary neurotrophic factor mRNA and protein expression and its upstream signalling pathway in cultured rat astroglial cells: possible implication of c-fos, Sp1 and p38MAPK.

Ciliary neurotrophic factor (CNTF) may be implicated in the pathogenetic mechanisms of hepatic encephalopathy. We tested this hypothesis by treating confluent primary cultures of rat astroglial cells with ammonium chloride for various periods and analysing the effect of ammonia on the signalling pathway that regulates CNTF mRNA and protein expression. Ammonia treatment induced a dose- and time-dependent reduction in CNTF mRNA and protein expression. Surface-enhanced laser desorption/ionization-time-of-flight mass spectrometry analysis of CNTF in the culture medium demonstrated that ammonia also induced a significant decrease in CNTF release. In addition, ammonia affected Sp1 and c-fos, transcription factors that regulate CNTF mRNA and protein expression, which showed partial dephosphorylation and significantly lower mRNA and protein levels. Total content of p38MAPK (for which Sp1 and c-fos are substrates) was unaffected by ammonia, although the diphosphorylated (active) form was significantly reduced after ammonia exposure.

Differential expression of Ran GTPase during HMBA-induced differentiation in murine erythroleukemia cells.

Murine erythroleukemia (MEL) cells undergo erythroid differentiation in vitro when treated with hexamethylene bisacetamide (HMBA). To identify genes involved in the commitment of MEL cells to differentiate, we screened a cDNA library constructed from HMBA-induced cells by differential hybridization and isolated GTPase Ran as a down-regulated gene. We observed that Ran was expressed in a biphasic mode. Following a decrease in mRNA level during the initial hours of induction, Ran re-expressed at 24-48 h, and gradually declined again. To investigate the role of Ran during MEL differentiation we constructed MEL transfectants capable to express or block Ran mRNA production constitutively. No effects were observed on cell growth and proliferation. Blockage of Ran, however, interfered with MEL cell differentiation resulting in a decrease of cell survival in the committed population.

[Community activities in primary care in Spain. An analysis based on the network of the Program of Community Activities (PACAP)]. / Las actividades comunitarias en atención primaria en España. Un análisis a partir de la Red del Programa de Actividades Comunitarias (PACAP).

OBJECTIVE: To describe, analyse and discuss the activities in the Network of Community Activities of the Programme of Community Activities in Primary Care of the Spanish Society of Family and Community Medicine. DESIGN: Description of the activities within this Network.Setting. Network of Community Activities of the Spanish Society of Family and Community Medicine. MAIN MEASUREMENTS: Specifications of the variables of geography, target population and experience descriptives were obtained from the qualitative analysis of the activity summary composed by its authors. The measurements are frequency tables expressed in graphs and analysis of the summaries contributed by the groups on objectives, kinds of programme, methodologies, evaluation and conclusions reached. The community orientation activities undertaken by the health centres registered on the Network came mostly (54%) from the autonomous communities of Madrid and Andalusia. A great many of them were aimed at the adult population, tackling problems of chronic diseases, and particularly at women, in this case tackling gender themes such as menopause and pregnancy, etc. CONCLUSIONS: There was uneven distribution between autonomous communities of the experiences included on the web. Central to community orientation are the replies to questions such as: inside or out of the health centre?, the importance of transferring leadership to society, and adaptation to the needs and demands of the population cared for.

Ilf2 is regulated during meiosis and associated to transcriptionally active chromatin.

Analysis of gene expression during testis development demonstrated accumulation of Ilf2 mRNA in pachytene spermatocytes. In these cells, the protein was localized in the nucleus, but it was absent from chromatin of the XY pachytene bivalent, in which there is no transcriptional activity. Nucleolar signal is inmmunolocalized in spermatogonia, Sertoli cells and oocytes. By in situ hybridisation, Ilf2 expression is detected in proliferative cells of adult ovary and a defined pattern is also exhibited in different tissues of embryos. The presence of ILF2 in active chromatin is corroborated in NIH3T3 cultured cells after transfection with Ilf2-EGFP constructs.

[Being a male or female doctor is different in medical practice]. / Ser médico o médica marca diferencias en la práctica asistencial.

OBJECTIVES: To identify the differences between the clinical practice (conduct) of male and female doctors and its determining factors; and to find the variability in the various conducts studied which is explained by a set of variables, gender among them. DESIGN: Cross-sectional, multi-centre descriptive study. SETTING: Andalusian health centres with populations of over 100000 inhabitants. PARTICIPANTS: Selection of 159 primary care doctors with postgraduate training by means of simple randomised sampling. 56% were men, 44% women, with power of comparisons at 68%. MEASUREMENTS AND MAIN RESULTS: Self-administered questionnaire to measure the dependent variable, overall conduct (clinical practice) and 11 dimensions of this conduct. Independent variables were: determinants of conduct identified by the theory of reasoned action (attitudes and subjective norm) and by the theory of social learning (self-efficacy and control locus), gender and other social and demographic variables and work conditions variables. Multiple linear regression models were constructed to explain each conduct analysed. Being a female doctor affects positively overall conduct and conduct in information, psycho-social guidance, prevention of obesity, active recruitment for family planning and collaboration with nurses. CONCLUSIONS: In Andalusia women general practitioners have a more marked orientation towards the psycho-social sides of care than their male colleagues. They give more information to their patients and more frequently perform preventive activities linked to their gender. They also rely on the work of their nurses more than male doctors.

Ser médico o médica marca diferencias en la práctica asistencial / Being a male or female doctor marks differences in care practice

Objetivos. Identificar las diferencias existentes entre médicos y médicas en la práctica clínica (conducta) y en sus determinantes, y conocer la variabilidad de las diferentes conductas estudiadas que es explicada por un conjunto de variables, entre ellas el género. Diseño. Estudio descriptivo, transversal, multicéntrico. Emplazamiento. Centros de salud andaluces de poblaciones de más de 100.000 habitantes. Participantes. Selección de 159 médicos de atención primaria con formación posgraduada mediante muestreo aleatorio simple; 56 por ciento, varones; 44 por ciento, mujeres; potencia de las comparaciones, 68 por ciento. Mediciones y resultados principales. Cuestionario autoadministrado para medir la variable dependiente, conducta global (práctica clínica) y 11 dimensiones de ésta, así como las variables independientes: determinantes de la conducta identificados por la teoría de la acción razonada -actitudes y norma subjetiva- y por la teoría del aprendizaje social -autoeficacia y locus de control-, el sexo y otras variables sociodemográficas y de las condiciones de trabajo. Se construyen modelos de regresión lineal múltiple para explicar cada conducta analizada. Ser médica influye de forma positiva en la conducta global y en las conductas de información, la conducta de orientación psicosocial, la conducta de prevención de la obesidad, la conducta de captación activa para planificación familiar y la conducta de colaboración con la enfermera. Conclusiones. Las médicas de familia en Andalucía presentan una orientación más acusada hacia los aspectos psicosociales de la atención que sus colegas varones, proporcionan más información a sus pacientes y realizan con más frecuencia actividades preventivas congruentes con su sexo. Además cuentan con las enfermeras para trabajar más que los médicos (AU)

Gene trap analysis of germ cell signaling to Sertoli cells: NGF-TrkA mediated induction of Fra1 and Fos by post-meiotic germ cells.

Analysis of complex signalisation networks involving distinct cell types is required to understand most developmental processes. Differentiation of male germ cells in adult mammals involves such a cross-talk between Sertoli cells, the somatic component which supports and controls germinal differentiation, and germ cells at their successive maturation stages. We developed a gene trapping strategy to identify genes, which, in Sertoli cells, are either up- or down-regulated by signals emitted by the germinal component. A library of approximately 2,000 clones was constituted from colonies independently selected from the Sertoli line 15P-1 by growth in drug-containing medium after random integration of a promoter-less (beta)geo transgene (neo(r)-lacZ fusion), which will be expressed as a fusion transcript from a 'trapped' cellular promoter, different in each clone. A first screen conducted on 700 events identified six clones in which beta-galactosidase activity was increased and one in which it was repressed upon addition of germ cells. The targeted loci were identified by cloning and sequencing the genomic region 5' of the insert. One of them was identified as the gene encoding Fra1, a component of the AP1 transcription regulatory complex. Accumulation of Fra1 mRNA was induced, both in 15P-1 and in freshly explanted Sertoli cells, by addition of either round spermatids or nerve growth factor (NGF). The effect of NGF was mediated by the TrkA receptor and the ERK1-ERK2 kinase kinase pathway. Fos and Fra1 transcription were induced within the first hour after addition of the neurotrophin, but, unlike what is observed after serum induction in the same cells, a second wave of transcription of Fra1, but not of Fos, started 16 hours later and peaked at higher levels at about 20 hours. These results suggest that AP1 activation may be an important relay in the Sertoli-germ cell cross-talk, and validate the gene trapping approach as a tool for the identification of target genes in cell culture systems.

Fhx (Foxj2) expression is activated during spermatogenesis and very early in embryonic development.

FHX (FOXJ2) is a recently characterized human fork head transcriptional activator that binds DNA with a dual sequence specificity. We have cloned the cDNA for the mouse orthologue Foxj2 and characterized its expression in the gonads and along the early pre-implantation development of the mouse. In the testis, Foxj2 is expressed from pachytene spermatocytes to round spermatids, but not in spermatogonia. In addition to the germ lineage, only Sertoli cells of the testis showed expression of Foxj2. In the ovary, only granulosa cells of the follicles express the factor. Neither mature spermatozoa nor oocytes showed expression of Foxj2. Foxj2 expression is early activated in zygotic development, being detected since as early as 8-cell stage embryos. Both cell layers of the blastocyst: the trophectoderm (TE) and the inner cell mass (ICM), express Foxj2.

DNA polymerase lambda (Pol lambda), a novel eukaryotic DNA polymerase with a potential role in meiosis.

A new gene (POLL) encoding a novel DNA polymerase (Pol lambda) has been identified at mouse chromosome 19. Murine Pol lambda, consisting of 573 amino acid residues, has a 32% identity to Pol beta, involved in nuclear DNA repair in eukaryotic cells. It is interesting that Pol lambda contains all the critical residues involved in DNA binding, nucleotide binding and selection, and catalysis of DNA polymerization, that are conserved in Pol beta and other DNA polymerases belonging to family X. Murine Pol lambda, overproduced in Escherichia coli, displayed intrinsic DNA polymerase activity when assessed by in situ gel analysis. Pol lambda also conserves the critical residues of Pol beta required for its intrinsic deoxyribose phosphate lyase (dRPase) activity. The first 230 amino acid residues of Pol lambda, that have no counterpart in Pol beta, contain a BRCT domain, present in a variety of cell-cycle check-point control proteins responsive to DNA damage and proteins involved in DNA repair. Northern blotting, in situ hybridization analysis and immunostaining showed high levels of Pol lambda specifically expressed in testis, being developmentally regulated and mainly associated to pachytene spermatocytes. These first evidences, although indirect, suggest a potential role of Pol lambda in DNA repair synthesis associated with meiosis.

[Family caregivers of people with neurodegenerative disease: profile, contributions, and impact of care]. / Cuidadores familiares de personas con enfermedad neurodegenerativa: perfil, aportaciones e impacto de cuidar.

OBJECTIVE: To analyse the informal system of caring for people with neuro-degenerative disease: what it consists of and the characteristics of main carers, the type of care given, and the consequences for the main carer of assuming these functions. DESIGN: Descriptive cross-sectional study conducted by means of a home-filled questionnaire. SETTING: Autonomous Community of Andalusia. PARTICIPANTS: 72 main carers of someone with neuro-degenerative disease, chosen from a sub-sample of 1000 homes in which at least one dependent person lives and receives care from a member of his/her family or social network with whom he/she resides. This sub-sample was based on a random sample of 3160 Andalusian homes stratified proportionately according to province and size of dwelling. MAIN RESULTS: In 86.1% of the 72 homes polled, health care was provided only by the informal system network. In over half the homes, care was provided by just one person, the main carer. The main carer was usually a woman (87.4%), with an average age of 54.52, house-wife and close family member of the sick person. In our study the beneficiaries of care had an average age of 77.63, a low level of autonomy in daily activities, and had had a neuro-degenerative disease for an average of 8.16 years. The main kinds of care provided in the home for people with neuro-degenerative disease were help in instrumental activities, care related to daily activities, observation/company and supervision of medicines. Main carers believed that undertaking this work had seriously affected their health (72.2%), the use they made of their time (84.7%), their social life (83.3%) and their economic position (44.4%). CONCLUSIONS: People with neuro-degenerative disease make considerable demands on health care provision, which is mainly covered at home by the immediate family network. In most cases this network consists of just one person, the main carer, on whom falls the entire burden of care. The assumption of this role directly affects the health of a large number of carers, as well as other areas of their lives, in particular the possibility of conducting a social life and using their time for themselves or for activities other than caring.

Cuidadores familiares de personas con enfermedad neurodegenerativa: perfil, aportaciones e impacto de cuidar / Family carers of people with neuro-degenerative illness: profile, contributions and impact of care

Objetivo. Analizar el sistema informal de cuidados de personas con enfermedad neurodegenerativa, en cuanto a su composición y a las características de los cuidadores principales, el tipo de cuidados que presta y las consecuencias que tiene para el cuidador principal asumir estas funciones. Diseño. Estudio descriptivo de corte transversal realizado mediante cuestionario domiciliario. Emplazamiento. Comunidad Autónoma de Andalucía. Participantes. Setenta y dos cuidadores principales de alguna persona con enfermedad neurodegenerativa, seleccionados de una submuestra de 1.000 hogares en los que vive al menos una persona dependiente por alguna razón y que recibe cuidados de algún miembro de su red familiar o social con el que reside. Esta submuestra se obtuvo a partir de una muestra aleatoria de 3.160 hogares andaluces, estratificada proporcionalmente según provincia y tamaño de hábitat. Resultados principales. En un 86,1 por ciento de los 72 hogares encuestados, los cuidados de salud son prestados sólo por la red el sistema informal. En más de la mitad de los hogares los cuidados son realizados por una sola persona, el cuidador principal. Éste suele ser una mujer (87,4 por ciento), con una edad media de 54,52 años, ama de casa y familiar cercano de la persona afectada. Los beneficiarios de nuestro estudio tienen una edad media de 77,63 años, un nivel bajo de autonomía para actividades de la vida diaria y enfermedad neurodegenerativa desde hace una media de 8,16 años. Los principales cuidados que se prestan en el hogar a personas con enfermedad neurodegenerativa son ayuda en actividades instrumentales, cuidados relacionados con actividades de la vida diaria, vigilancia/acompañamiento y administración de la toma de medicamentos. Las cuidadoras principales consideran que desempeñar este trabajo ha afectado de forma importante a su salud (72,2 por ciento), al uso que hacen de su tiempo (84,7 por ciento), a su vida social (83,3 por ciento) y a su situación económica (44,4 por ciento). Conclusiones. Las personas con enfermedad neurodegenerativa presentan una importante demanda de cuidados de atención a la salud, que en gran parte es cubierta en el hogar por su red familiar inmediata. En la mayoría de los casos esta red se halla configurada por una sola persona, la cuidadora principal, sobre la que recae toda la carga de los cuidados. Para un importante grupo de cuidadoras, asumir este rol afecta de forma directa a su salud, así como a otras áreas de su vida y, en especial, a sus posibilidades de tener relaciones sociales y de usar el tiempo para sí mismas o para otras actividades diferentes a cuidar (AU)