Determining the value contribution of emicizumab (Hemlibra®) for the prophylaxis of haemophilia A with inhibitors in Spain by multi-criteria decision analysis

Haemophilia A; Inhibitors; Drug valueHemofilia A; Inhibidores; Valores del medicamentoHemofília A; Inhibidors; Valors del medicamentPatients with moderate to severe haemophilia A are at a higher risk of developing FVIII inhibitors that require the use of more costly and less effective treatments. The objective of this study was to determine the value of emicizumab for the prophylaxis of haemophilia A with inhibitors compared to the current therapeutic alternatives, activated prothrombin complex concentrate and recombinant factor VIIa through reflective Multi-Criteria Decision Analysis. The EVIDEM framework adapted to orphan drugs and weighted by a sample of 98 national and regional Spanish evaluators was used. Two structured evidence matrices were developed: emicizumab against activated prothrombin complex concentrate and emicizumab against recombinant factor VIIa. A multidisciplinary team of haemophilia experts rated each of the criteria. Mean and standard deviation were calculated by each criterion and discussed among all participants. Haemophilia A with inhibitors was perceived as a severe disease with high unmet needs. Emicizumab was rated with higher efficacy, therapeutic benefit and quality of life than comparators. When administered alone for the prevention of bleeding events, emicizumab had slightly better safety and tolerability profile than activated prothrombin complex concentrate and similar with recombinant factor VIIa. The inclusion of emicizumab in clinical practice guidelines was valued positively by the members of the panel. Overall, value of emicizumab was higher than activated prothrombin complex concentrate and recombinant factor VIIa, mostly because of efficacy and therapeutic benefit in reducing treated haemorrhages. Reflective Multi-Criteria Decision Analysis has proven to be a feasible method to determine the value contribution of comparative therapies in haemophilia.This work was supported by Hoffmann-La Roche

Lack of association between endothelial nitric oxide synthase (NOS3) gene polymorphisms and suicide attempts

<p>Abstract</p> <p>Objective</p> <p>The aim of this study is to investigate the association between two polymorphisms of endothelial nitric oxide synthase (NOS3) and suicide attempts.</p> <p>Methods</p> <p>We genotyped 186 suicide attempters and 420 unrelated healthy controls. The following polymorphisms were analysed: T-786C and 27-bp repeat in intron 4.</p> <p>Results</p> <p>No significant differences were found in genotype or in allelic distribution of the aforesaid polymorphisms. There were also no differences in the genotype distribution or allelic frequencies when separately assessing males and females or impulsive and non-impulsive attempters and normal controls. Estimated haplotype frequencies were similar in both groups.</p> <p>Conclusion</p> <p>Our data do not support the hypothesis that genetically determined changes in the NOS3 gene confer increased susceptibility for suicidal behavior.</p

Suicide in pregnant women : experiences and support networks for the surviving families

ABSTRACT: To describe the experiences of the families of two pregnant women who committed suicide in the Department of Antioquia (Colombia) during 2010-2011. Methodology: a qualitative study using the hermeneutic phenomenological approach, specifically the case study method. Three to four interviews were conducted with each family. These interviews were later systematized using the Atlas ti software. Results: the category “family experience in the event of suicide: on how to become a learner” was found in the family of Bella, and two categories emerged from it: 1. “Her death affected us both internally and externally.” 2. “Between deafness and the power of the support networks.” In the family of Consentida, the “family experience: how to survive pain” category emerged, and additionally, two tendencies derived from it: 1. “Expanding and breaking networks.” 2. “Tying up loose ends.” Conclusions: the studied families have overcome the event as they have earned the recognition of collaborative, empowering and linking networks, which have remained throughout time. In their experience, the families have managed to distance themselves from the choice of their pregnant relatives and have thus bravely overcome their loss.RESUMEN: Describir la vivencia que han tenido las familias de dos mujeres gestantes alrededor de su muerte por suicidio en el Departamento de Antioquia (Colombia) durante el año 2010-2011. Metodología: investigación cualitativa, método fenomenológico-hermenéutico, específicamente estudio de casos. Se realizaron entre tres y cuatro entrevistas con cada familia y posteriormente se sistematizaron bajo el software Atlas ti. Resultados: en la familia de Bella se encontró la categoría: la vivencia familiar frente al suicidio: de cómo tornarse aprendiz; de ésta surgieron dos categorías: 1). Su muerte nos afectó por dentro y por fuera; 2). entre la sordera y la potencia de las redes de apoyo. En la familia de Consentida emerge la categoría la vivencia familiar: cómo sobrevivir al dolor, a su vez de ella se derivan dos tendencias: 1). Ampliando y rompiendo redes: 2). atando cabos. Conclusiones: las familias del estudio han ido sobreponiéndose al evento en tanto han logrado reconocimiento por parte de redes colaborativas, potenciadoras y vinculantes que han permanecido a lo largo del tiempo. En su vivencia las familias han logrado tomar distancia de la elección de sus familiares gestantes y han seguido valientemente sobreponiéndose a su pérdida

Lithium therapy and weight change in people with bipolar disorder: A systematic review and meta-analysis

Lithium remains the gold standard maintenance treatment for Bipolar Disorder (BD). However, weight gain is a side effect of increasing relevance due to its metabolic implications. We conducted a systematic review and metaanalysis aimed at summarizing evidence on the use of lithium and weight change in BD. We followed the PRISMA methodology, searching Pubmed, Scopus and Web of Science. From 1003 screened references, 20 studies were included in the systematic review and 9 included in the meta-analysis. In line with the studies included in the systematic review, the meta-analysis revealed that weight gain with lithium was not significant, noting a weight increase of 0.462 Kg (p = 0158). A shorter duration of treatment was significantly associated with more weight gain. Compared to placebo, there were no significant differences in weight gain. Weight gain was significantly lower with lithium than with active comparators. This work reveals a low impact of lithium on weight change, especially compared to some of the most widely used active comparators. Our results could impact clinical decisions

Relationships between social withdrawal and facial emotion recognition in neuropsychiatric disorders

Background: Emotion recognition constitutes a pivotal process of social cognition. It involves decoding social cues (e.g., facial expressions) to maximise social adjustment. Current theoretical models posit the relationship between social withdrawal factors (social disengagement, lack of social interactions and loneliness) and emotion decoding. Objective: To investigate the role of social withdrawal in patients with schizophrenia (SZ) or probable Alzheimer's disease (AD), neuropsychiatric conditions associated with social dysfunction. Methods: A sample of 156 participants was recruited: schizophrenia patients (SZ; n = 53), Alzheimer's disease patients (AD; n = 46), and two age-matched control groups (SZc, n = 29; ADc, n = 28). All participants provided self-report measures of loneliness and social functioning, and completed a facial emotion detection task. Results: Neuropsychiatric patients (both groups) showed poorer performance in detecting both positive and negative emotions compared with their healthy counterparts (p < .01). Social withdrawal was associated with higher accuracy in negative emotion detection, across all groups. Additionally, neuropsychiatric patients with higher social withdrawal showed lower positive emotion misclassification. Conclusions: Our findings help to detail the similarities and differences in social function and facial emotion recognition in two disorders rarely studied in parallel, AD and SZ. Transdiagnostic patterns in these results suggest that social withdrawal is associated with heightened sensitivity to negative emotion expressions, potentially reflecting hypervigilance to social threat. Across the neuropsychiatric groups specifically, this hypervigilance associated with social withdrawal extended to positive emotion expressions, an emotional-cognitive bias that may impact social functioning in people with severe mental illness

Cortical thinning over two years after first-episode psychosis depends on age of onset

First-episode psychosis (FEP) patients show structural brain abnormalities at the first episode. Whether the cortical changes that follow a FEP are progressive and whether age at onset modulates these changes remains unclear. This is a multicenter MRI study in a deeply phenotyped sample of 74 FEP patients with a wide age range at onset (15–35 years) and 64 neurotypical healthy controls (HC). All participants underwent two MRI scans with a 2-year follow-up interval. We computed the longitudinal percentage of change (PC) for cortical thickness (CT), surface area (CSA) and volume (CV) for frontal, temporal, parietal and occipital lobes. We used general linear models to assess group differences in PC as a function of age at FEP. We conducted post-hoc analyses for metrics where PC differed as a function of age at onset. We found a significant age-by-diagnosis interaction effect for PC of temporal lobe CT (d = 0.54; p = 002). In a post-hoc-analysis, adolescent-onset (≤19 y) FEP showed more severe longitudinal cortical thinning in the temporal lobe than adolescent HC. We did not find this difference in adult-onset FEP compared to adult HC. Our study suggests that, in individuals with psychosis, CT changes that follow the FEP are dependent on the age at first episode, with those with an earlier onset showing more pronounced cortical thinning in the temporal lobe

I Diretriz brasileira de cardio-oncologia pediátrica da Sociedade Brasileira de Cardiologia

Sociedade Brasileira de Oncologia PediátricaUniversidade Federal de São Paulo (UNIFESP) Instituto de Oncologia Pediátrica GRAACCUniversidade Federal de São Paulo (UNIFESP)Universidade de São Paulo Faculdade de Medicina Instituto do Coração do Hospital das ClínicasUniversidade Federal do Rio Grande do Sul Hospital de Clínicas de Porto AlegreInstituto Materno-Infantil de PernambucoHospital de Base de BrasíliaUniversidade de Pernambuco Hospital Universitário Oswaldo CruzHospital A.C. CamargoHospital do CoraçãoSociedade Brasileira de Cardiologia Departamento de Cardiopatias Congênitas e Cardiologia PediátricaInstituto Nacional de CâncerHospital Pequeno PríncipeSanta Casa de Misericórdia de São PauloInstituto do Câncer do Estado de São PauloUniversidade Federal de São Paulo (UNIFESP) Departamento de PatologiaHospital Infantil Joana de GusmãoUNIFESP, Instituto de Oncologia Pediátrica GRAACCUNIFESP, Depto. de PatologiaSciEL

una mirada desde las Ciencias de la Conducta

Este libro es el resultado de los trabajos presentados en el 1er Congreso Internacional "Convivencia y bienestar con sentido humanista para una cultura de paz"

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality