Evaluation of two treatment strategies for the prevention of preterm birth in women identified as at risk by ultrasound (PESAPRO Trial): Study protocol for a randomized controlled trial

Background: Premature birth is considered one of the main problems in modern Obstetrics. It causes more than 50 % of neonatal mortality; it is responsible for a large proportion of infant morbidity and incurs very high economic costs. Cervical length, which can be accurately measured by ultrasound, has an inverse relationship with the risk of preterm birth. As a result, having an effective intervention for asymptomatic patients with short cervix could reduce the prematurity. Although recently published data demonstrates the effectiveness of vaginal progesterone and cervical pessary, these treatments have never been compared to one another. Methods/Design: The PESAPRO study is a noncommercial, multicenter, open-label, randomized clinical trial (RCT) in pregnant women with a short cervix as identified by transvaginal ultrasonography at 19 to 22 weeks of gestation. Patients are randomized (1:1) to either daily vaginal progesterone or cervical pessary until the 37th week of gestation or delivery; whichever comes first. During the trial, women visit every 4 weeks for routine questions and tests. The primary outcome is the proportion of spontaneous preterm deliveries before 34 weeks of gestation. A sample size of 254 pregnant women will be included at 29 participating hospitals in order to demonstrate noninferiority of placing a pessary versus vaginal progesterone. The first patient was randomized in August 2012, and recruitment of study subjects will continue until the end of December 2015. Discussion: This trial assesses the comparative efficacy and safety between two accepted treatments, cervical pessary versus vaginal progesterone, and it will provide evidence in order to establish clinical recommendationsThe study has been funded by two national grants from the Spanish Ministry of Health and ISCIII

Anesthesic and surgical guidelines for the treatment of the ascending aorta andaortic arch. Consensus document of the Spanish Societies of Anesthesia and Cardiovascular Surgerya

La patología de la aorta supone un reto para la medicina. Tanto a nivel diagnóstico, como terapéutico,el volumen de variables implicado ha hecho que dicha patología sea abordada por una ingente cantidad de especialistas. El manejo quirúrgico de dichas patologías implica un esfuerzo extraordinario por parte de muchos profesionales, dada la complejidad técnica y tecnológica empleada. A lo largo de estos a˜nos,dichos esfuerzos están dando sus frutos en forma de mejoras de resultados, gracias a un abordaje sis-temático y protocolizado en el seno de un grupo de expertos (Comités de aorta o “Aortic team”) en el que se han de implicar cardiólogos, cirujanos cardíacos, cirujanos vasculares, anestesiólogos y radiólogos, principalmente. En este documento, consensuado entre los grupos de trabajo de Aorta de las sociedades españolas de Anestesiología (SEDAR) y Cirugía Torácica-cardiovascular (SECTCV) se busca difundir los modos de trabajo más consensuados entre los centros de mayor actividad del país por parte de ambas especialidades, en lo que al tratamiento quirúrgico se refiere de la patología de aorta ascendente y arco aórtico se refiere, así como del tratamiento de la disección aguda de aorta. Somos conscientes de la evolución constante de la terapéutica, lo cual sin duda puede hacer cuestionables algunas opiniones aquí expresadas y que sin duda irán modificándose en futuras edicionestThe pathology of the aorta is a challenge for medicine. Diagnostic and therapeutica move a huge volumeof variables. This has let this pathology to be addressed by a big number of specialists. The surgicalmanagement of these pathologies implies an extraordinary effort on the part of many professionals,given the technical and technological complexity employed. Throughout these years, these efforts arepaying off in the form of improved results, thanks to a systematic and protocolized approach within agroup of experts (Aortic Committees or “Aortic team”) in which they have to involve cardiologists, cardiacsurgeons, vascular surgeons, anesthesiologists and radiologists, mainly.In this document, agreed between the Aorta working groups of the Spanish societies of Anesthesiology(SEDAR) and Thoracic-Cardiovascular Surgery (SECCE), it is sought to disseminate the most agreed work-ing modes among the centers of greatest activity in the country by both specialties, as far as surgicaltreatment is concerned with ascending aortic and aortic arch pathology, as well as the treatment of acuteaortic dissection.We are aware of the constant evolution of therapeutics, which can undoubtedly make some of the opinionsexpressed here questionable and that will undoubtedly be modified in future editions.This document aims to be a working tool for the different professionals involved in the treatment of aorticpathology

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Estudio piloto sobre uma medida específica para as perturbações do sono associadas à doença de Parkinson: SCOPA-sono

Introducción. En la enfermedad de Parkinson (EP) existe una alta prevalencia de trastornos del sueño. Objetivos. Comprobar los atributos métricos básicos de la escala SCOPA-sueño para pacientes con EP; objetivo secundario: analizar el impacto del trastorno del sueño en la calidad de vida relacionada con la salud (CVRS) del paciente y de su cuidador principal. Sujetos y métodos. 68 pacientes con EP y sus cuidadores principales. Se aplicaron: Hoehn y Yahr, SCOPA-motor, impresión clínica de gravedad (CISIPD), escala PDSS, Hospital Anxiety and Depression Scale, SCOPA-psicosocial y EuroQoL. El cuidador cumplimentó un cuestionario PDSS sobre el sueño del paciente y las medidas de la CVRS (SF-36, EuroQoL). Se analizaron la aceptabilidad, las asunciones escalares, la consistencia interna, la validez de constructo y la precisión de la SCOPA-sueño. Resultados. La SCOPA-sueño mostró aceptabilidad satisfactoria y asunciones escalares. La subescala sueño nocturno (SC-Sn) presentó leve efecto techo (22,1%), y la subescala somnolencia diurna (SC-Sd), defectuosa validez convergente del ítem 6; la consistencia interna de ambas resultó satisfactoria (alfa = 0,84 y 0,75, respectivamente). SC-Sn correlacionó significativamente con la PDSS (rS= –0,70) y con el cuestionario PDSS cumplimentado por el cuidador (rS = –0,53), y fueron menores los valores respectivos para la SC-Sd (rS= –0,41 y –0,50). Error estándar de la medida: SC-Sn, 1,45; SC-Sd, 1,76. La CVRS del paciente y la del cuidador mostraron una escasa correlación con las medidas de sueño. Conclusiones. La escala SCOPA-sueño es viable, consistente y útil para evaluar el trastorno del sueño en pacientes con EP. La relación entre la CVRS y la alteración del sueño fue débil. [REV NEUROL 2006; 43: 577-83]Introduction. There is a high prevalence of sleep disorders in Parkinson’s disease (PD). Aims. To assess some basic metric attributes of the SCOPA-Sleep scale, a measure for PD patients; secondary objective: to check the impact caused by the sleep disorder on the health-related quality of life (HRQoL) of patients and their caregivers. Subjects and methods. 68 PD patients and their main caregivers; measures: Hoehn and Yahr staging, SCOPA-Motor, Clinical Impression of Severity Index (CISI-PD), PDSS, Hospital Anxiety and Depression Scale, SCOPA-Psychosocial, and EuroQoL. Carers filled in a PDSS questionnaire about patient sleep and HRQoL measures (SF-36, EuroQoL). SCOPA-Sleep acceptability, scaling assumptions, internal consistency, construct validity and precision were determined. Results. SCOPA-Sleep acceptability and scaling assumptions resulted satisfactory, although the nocturnal sleep subescale (SC-Ns) showed a mild ceiling effect (22.1%) and a defective convergent validity was found for daytime sleepiness (SC-Ds) item 6. Internal consistency also was satisfactory for both scales (alpha = 0.84 and 0.75, respectively). The correlation between SC-Ns and PDSS was high (rS = –0.70), as it was between SC-Ns and PDSS questionnaire by caregiver (rS = –0.53). The corresponding coefficients with the SC-Ds gained lower values (rS = –0.41 y –0.50). Standard error of measurement was 1.45 for the SC-Ns and 1.76 for the SC-Ds. Both, patient and caregiver HRQoL showed a loose association with the sleep measures. Conclusion. SCOPA-Sleep is a feasible, consistent, and useful scale for assessment of sleep disorder in PD patients. A weak association between sleep disorder and HRQoL was found. [REV NEUROL 2006; 43: 577-83]Introdução. A doença de Parkinson (DP) associa-se a uma elevada prevalência de perturbações do sono. Objectivos. Comprovar os atributos métricos básicos da escala SCOPA-sono para doentes com DP; objectivo secundário: analisar o impacto das perturbações do sono na qualidade de vida relacionada com a saúde (QVRS) do doente e do seu principal cuidador. Sujeitos e métodos. Foram estudados 68 doentes com DP e respectivos cuidadores. Aplicaramse as escalas: Hoehn e Yahr, SCOPA-motor, Clinical Impression of Severity Index for Parkinson’s Disease (CISI-PD), escala PDSS, Hospital Anxiety and Depression Scale, SCOPA-psicosocial e EuroQoL. O cuidador preencheu um questionário PDSS sobre o sono do doente e as medidas da QVRS (SF-36, EuroQoL). Foram analisadas a aceitabilidade, as assunções escalares a consistência interna, a validade de construção e a precisão da SCOPA-sono. Resultados. A SCOPA-sono revelou aceitabilidade satisfatória e assunções das escalas. A subescala sono nocturno (SC-Sn) apresentou um discreto efeito tecto (22,1%) e a subescala sonolência diurna (SC-Sd) uma validade convergente imperfeita do item 6; a consistência interna de ambas resultou satisfatória (alfa = 0,84 e 0,75, respectivamente). SC-Sn correlacionou-se significativamente com a PDSS (rS = –0,70) e com o questionário PDSS preenchido pelo cuidador (rS = –0,53), e foram menores os valores respectivos para a SC-Sd (rS = –0,41 e –0,50). O erro standard das medidas foi: SC-Sn, 1,45; SC-Sd, 1,76. A QVRS do doente e do cuidador revelou uma ténue correlação com as medidas do sono. Conclusões. A escala SCOPA-sono é viável, consistente e útil para avaliar a perturbação do sono em doentes com DP. Detectou-se uma ténue relação entre a QVRS e a alteração do sono. [REV NEUROL 2006; 43: 577-83

Estudio longitudinal de doentes com doença de Parkinson (ELEP): objectivos e metodologia

La enfermedad de Parkinson (EP) es crónica y progresiva. Desde la perspectiva sociosanitaria, representa una fuente de sufrimiento para el paciente y sus cuidadores, así como una importante carga para la sociedad. La información actual sobre la EP es limitada en cuanto al conocimiento del curso evolutivo relacionado con: 1) el desarrollo y la evolución de los aspectos no motores de la enfermedad; 2) el impacto de estas manifestaciones sobre la discapacidad y la calidad de vida relacionada con la salud (CVRS); 3) los determinantes de la discapacidad y de la pérdida de CVRS; 4) los factores relacionados con la velocidad de progresión de la enfermedad; 5) las pautas de aplicación y la repercusión diferencial a largo plazo (sobre complicaciones, discapacidad, CVRS) de las medidas terapéuticas disponibles; y 6) el impacto de la EP sobre los cuidadores. Además, en la información existente se detecta heterogeneidad en la calidad de las propiedades métricas de los instrumentos de medida aplicados y de los sesgos de selección.Parkinson’s disease (PD) is a chronic and progressive disorder. It produces a significant burden not only for patients, but also for their family and caregivers, with a major socio-economic impact on society. Current knowledge on PD is characterized by scarce information about the evolutionary course of: 1) the non-motor PD features; 2) impact of non-motor PD features on disability and health related quality of life (HRQL) impairment; 3) factors related to disability and HRQL determinants; 4) factors that speed or slow the progression of PD; 5) differential long-term effect of available PD therapeutic schedules and their relationships with disability, complications, and HRQL; and 6) impact of the disease on patients’ caregivers. In addition, heterogeneity in the metric quality of the applied measures and selection bias are frequently foundA doença de Parkinson (DP) é crónica e progresiva. De uma perspectiva socio-sanitária, representa uma fonte de sufrimento para o paciente e seus cuidadores, assim como uma carga importante para a sociedade. A informação actual sobre a DP é limitada em quanto ao conhecimento do curso evolutivo relacionado com: 1) o desenvolvimento e a evolução dos aspectos não motores da doença; 2) o impacto destas manifestações sobre a discapacidade e a qualidade de vida relacionada com a saúde (QVRS); 3) os determinantes da discapacidade e da diminuição de QVRS; 4) os factores relacionados com a velocidade de progressão da doença; 5) as pautas de aplicação e a repercursão diferencial a longo prazo (sobre complicações, discapacidade, QVRS) das medidas terapêuticas disponíveis; e 6) o impacto da DP sobre os cuidadores. Além disso, na informação disponível há uma heterogeneidade na qualidade das propriedades métricas dos instrumentos de medida aplicados e dos enviesamentos de selecção

Criação e protocolo de seguimento longitudinal de uma coorte multipropósito de doentes com doença de Parkinson de diagnóstico recente: projecto VIP

La enfermedad de Parkinson (EP) es una enfermedad neurodegenerativa muy heterogénea desde el punto de vista etiológico, clínico y terapéutico, lo que dificulta la interpretación de resultados de estudios transversales. Son necesarios los registros de pacientes y los estudios longitudinales de cohortes bien caracterizadas desde el punto de vista clínico y terapéutico.Parkinson’s disease (PD) is a quite heterogeneous disorder, thus difficulting the interpretation of transversal studies. Patients’ registries and longitudinal studies can be considered as a priority in order to understand many still unknown aspects of the disease.A doença de Parkinson (DP) é uma doença neurodegenerativa muito heterogénea do ponto de vista etiológico, clínico e terapêutico, o que dificulta a interpretação de resultados de estudos transversais. São necessários os registos de doentes e os estudos longitudinais de coortes bem caracterizadas do ponto de vista clínico e terapêutico