Los “puntos débiles o sensibles” de los ensayos clínicos en niñas/os y en adolescentes

La revisión ética de un ensayo clínico[1] que incluye a niñas/os y adolescentes en calidad de participantes, debe centrar su mirada en aspectos relacionados con la vulnerabilidad inherente a esa etapa de la vida, condición que se nutre de elementos biológicos, emocionales, de justicia y de equidad, entre otros.Sin embargo, la visión sugerida en este caso y sin desoír las características mencionadas, es la que busca profundizar en uno de los actores del proceso de investigación: el ensayo clínico.El objetivo es poder determinar la presencia o no de “zonas frágiles o de puntos débiles” en su interior, los que al ser individualizados y especialmente considerados, contribuyan a mejorar la calidad de la revisión ética de las investigaciones que son llevadas a cabo en niñas/os y adolescentes.[1] Las autoridades reguladoras españolas de acuerdo con el artículo 58 de la Ley 29/2006 de garantías y uso racional de los medicamentos y productos sanitarios de 26 julio de 2006 y el artículo 2 del Real Decreto 223/2004 de 6 de febrero de 2004 entienden por Ensayo Clínico: “ toda investigación efectuada en seres humanos, con el fin de determinar o confirmar los efectos clínicos, farmacológicos, y/o demás efectos farmacodinámicos, y/o de detectar las reacciones adversas, y/o de estudiar la absorción, distribución, metabolismo y eliminación de uno o varios medicamentos en investigación con el fin de determinar su seguridad y/o su eficacia ”. El carácter experimental del ensayo clínico obliga al investigador a considerar tres dimensiones: la metodológica o científica, la ética y la normativa o reguladora ya que se hace necesario proteger la integridad de los pacientes y sus derechos así como la fiabilidad de los datos, Sociedad Española de Farmacología Clínica, en www.se-fc.org/0301.php

Los “puntos débiles o sensibles” de los ensayos clínicos en niñas/os y en adolescentes

The ethical review of clinical research on children and adolescentsshould be centered in aspects related to their conditionof vulnerability, which is nurtured by biological, emotional,equity and justice elements.However, the suggested vision in this case, without overlookingpreviously mentioned characteristics, is the one thatseeks to delve deeper in one of the actors of the researchprocess: the clinical research protocol.The objective is to determine the presence or not of "fragilezones or weak spots" in its interior, that when individualizedand considered, will contribute to improve the quality of theethical review on children and adolescent research.La revisión ética de un ensayo clínico1 que incluye a niñas/os y adolescentes en calidad de participantes, debe centrar su mirada en aspectos relacionados con la vulnerabilidad inherente a esa etapa de la vida, condición que se nutre de elementos biológicos, emocionales, de justicia y de equidad, entre otros. Sin embargo, la visión sugerida en este caso y sin desoír las características mencionadas, es la que busca profundizar en uno de los actores del proceso de investigación: el ensayo clínico. El objetivo es poder determinar la presencia o no de “zonas frágiles o de puntos débiles” en su interior, los que al ser individualizados y especialmente considerados, contribuyan a mejorar la calidad de la revisión ética de las investigaciones que son llevadas a cabo en niñas/os y adolescentes

Retroviruses integrate into a shared, non-palindromic DNA motif.

Many DNA-binding factors, such as transcription factors, form oligomeric complexes with structural symmetry that bind to palindromic DNA sequences1. Palindromic consensus nucleotide sequences are also found at the genomic integration sites of retroviruses2-6 and other transposable elements7-9, and it has been suggested that this palindromic consensus arises as a consequence of the structural symmetry in the integrase complex2,3. However, we show here that the palindromic consensus sequence is not present in individual integration sites of human T-cell lymphotropic virus type 1 (HTLV-1) and human immunodeficiency virus type 1 (HIV-1), but arises in the population average as a consequence of the existence of a non-palindromic nucleotide motif that occurs in approximately equal proportions on the plus strand and the minus strand of the host genome. We develop a generally applicable algorithm to sort the individual integration site sequences into plus-strand and minus-strand subpopulations, and use this to identify the integration site nucleotide motifs of five retroviruses of different genera: HTLV-1, HIV-1, murine leukaemia virus (MLV), avian sarcoma leucosis virus (ASLV) and prototype foamy virus (PFV). The results reveal a non-palindromic motif that is shared between these retroviruses

Placental Pathology in Relation to Uterine Artery Doppler Findings in Pregnancies with Severe Intrauterine Growth Restriction and Abnormal Umbilical Artery Doppler Changes

OBJECTIVES: Current guidelines for diagnosis and management of early-onset intrauterine growth restriction (IUGR) rely on umbilical artery Doppler (UAD), without including uterine artery Doppler (UtAD). We hypothesized that IUGR cases with abnormal UAD but normal UtAD has a different spectrum of placental pathology compared with those with abnormal UtAD. STUDY DESIGN: Retrospective review of pregnancies with sonographic evidence of IUGR and abnormal UAD prior to delivery. Cases with ≥ 1 UtAD record(s) after 18(+0) weeks' gestation and placental pathology were included. Cases were stratified according to initial UtAD pulsatility index (PI) values (n = 196): normal (n = 19; PI < 95th centile for gestational age/no notching), intermediate (n = 69; PI ≥ 95th centile/no/unilateral notching) and abnormal (n = 108; PI ≥ 95th centile/bilateral notching). Pregnancy outcomes and placental pathology were compared between groups. RESULTS: Women in the normal group delivered later than those in the abnormal group (30.1 ± 3.5 vs. 28.0 ± 3.5 weeks; mean ± standard deviation; p = 0.03). Their placentas exhibited higher rates of chronic intervillositis (15.8 vs. 0.9%; p = 0.01), chorangiosis (15.8 vs. 0.9%; p < 0.0001), and massive perivillous fibrin deposition (21.1 vs. 7.4%; p = 0.05), but had lower rates of uteroplacental vascular insufficiency (26.3 vs. 79.6%; p < 0.0001). CONCLUSION: Approximately 10% of pregnancies with early-onset IUGR and abnormal UAD exhibited normal UtAD waveforms. They delivered later, and their placentas exhibited unusual placental pathologies

Time-to-birth prediction models and the influence of expert opinions

Preterm birth is the leading cause of death among children under five years old. The pathophysiology and etiology of preterm labor are not yet fully understood. This causes a large number of unnecessary hospitalizations due to high--sensitivity clinical policies, which has a significant psychological and economic impact. In this study, we present a predictive model, based on a new dataset containing information of 1,243 admissions, that predicts whether a patient will give birth within a given time after admission. Such a model could provide support in the clinical decision-making process. Predictions for birth within 48 h or 7 days after admission yield an Area Under the Curve of the Receiver Operating Characteristic (AUC) of 0.72 for both tasks. Furthermore, we show that by incorporating predictions made by experts at admission, which introduces a potential bias, the prediction effectiveness increases to an AUC score of 0.83 and 0.81 for these respective tasks