PROTEÇÃO AO MÍNIMO EXISTENCIAL NO CONTEXTO DA PANDEMIA DO COVID-19

O presente artigo analisa a suficiência das medidas de proteção social adotadas pelo Estado Brasileiro em razão da pandemiacausada pelo novo Coronavírus (SARS-CoV 2) para garantir o mínimo existencial. É dado enfoque nas medidas adotadas pela Lei nº 13.982, de 02 de abril de 2020, mais precisamente a criação do auxílio emergencial e a possibilidade de antecipação dos benefícios por incapacidade permanente e do benefício de prestação continuada (BPC), dado o fechamento das agências da previdência social e, por isso, a impossibilidade de realização das perícias necessárias para concessão desse benefício previdenciário e desse benefício assistencial, respectivamente. Para análise da suficiência das medidas adotadas, sob a ótica do mínimo existencial, são apresentados os valores que foram pagos ou antecipados em comparação com o salário-mínimo nacional. Com isso, é apresentada a seguinte reflexão. Essas medidas garantiram apenas a sobrevivência ou garantiram uma vidadigna. O método utilizado será o dedutivo, realizando pesquisa bibliográfica, partindo da coleta de conceitos doutrinários e informações jurídicas e legais

Caregiver burden, and parents' perception of disease severity determine health-related quality of life in paediatric patients with intoxication-type inborn errors of metabolism.

Background Living with a non-acute (phenylketonuria) or acute (e.g. urea cycle disorders, organic acidurias) intoxication-type inborn error of metabolism (IT-IEM) can have a substantial impact on health-related quality of life (HrQoL) of paediatric patients and their families. Parents take primary responsibility for treatment monitoring and experience worry and fear about their child's health status. Quantitative evidence on parental psychological factors which may influence the HrQoL of patients with IT-IEM are sparse to non-existent. Methods In this multicenter survey study 50 parents of IT-IEM patients (ages 5-19) assessed the severity of their child's disease, reported on caregiver burden, and proxy-rated their child's HrQoL. Additionally, 35 patient self-reports on HrQoL were obtained (n = 16 female patients, n = 19 male patients). Multiple linear regressions were conducted to examine the predictive power of child age, sex, medical diagnosis type (acute / non-acute), parental perceived disease severity and caregiver burden on patients' HrQoL. Mediation analyses were used to investigate the relation of caregiver burden and parental ratings of disease severity with patients' HrQoL. Results Significant regression models for self-reported [F(5,34) = 10.752, p < .001, R 2 adj.. = 0.59] and parent proxy reported HrQoL [F(5,49) = 20.513, p < .001, R 2 adj.. = 0.67] emerged. High caregiver burden and perceived disease severity predicted significantly lower patient self- and proxy-reported HrQoL while type of diagnosis (acute versus non-acute) did not. Female sex predicted significantly lower self-reported HrQoL. High caregiver burden was the mediating factor between high perceived severity of the child's disease and lower proxy- by parent rated HrQoL. Conclusion Detecting elevated burden of care and providing support for parents seems crucial to prevent adverse consequences for their children's HrQoL. Intervention studies are needed, to assess which support programs are most efficient

Genes to Diseases (G2D) Computational Method to Identify Asthma Candidate Genes

Asthma is a complex trait for which different strategies have been used to identify its environmental and genetic predisposing factors. Here, we describe a novel methodological approach to select candidate genes for asthma genetic association studies. In this regard, the Genes to Diseases (G2D) computational tool has been used in combination with a genome-wide scan performed in a sub-sample of the Saguenay−Lac-St-Jean (SLSJ) asthmatic familial collection (n = 609) to identify candidate genes located in two suggestive loci shown to be linked with asthma (6q26) and atopy (10q26.3), and presenting differential parent-of-origin effects. This approach combined gene selection based on the G2D data mining analysis of the bibliographic and protein public databases, or according to the genes already known to be associated with the same or a similar phenotype. Ten genes (LPA, NOX3, SNX9, VIL2, VIP, ADAM8, DOCK1, FANK1, GPR123 and PTPRE) were selected for a subsequent association study performed in a large SLSJ sample (n = 1167) of individuals tested for asthma and atopy related phenotypes. Single nucleotide polymorphisms (n = 91) within the candidate genes were genotyped and analysed using a family-based association test. The results suggest a protective association to allergic asthma for PTPRE rs7081735 in the SLSJ sample (p = 0.000463; corrected p = 0.0478). This association has not been replicated in the Childhood Asthma Management Program (CAMP) cohort. Sequencing of the regions around rs7081735 revealed additional polymorphisms, but additional genotyping did not yield new associations. These results demonstrate that the G2D tool can be useful in the selection of candidate genes located in chromosomal regions linked to a complex trait

Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

ARDD 2020: from aging mechanisms to interventions

Aging is emerging as a druggable target with growing interest from academia, industry and investors. New technologies such as artificial intelligence and advanced screening techniques, as well as a strong influence from the industry sector may lead to novel discoveries to treat age-related diseases. The present review summarizes presentations from the 7th Annual Aging Research and Drug Discovery (ARDD) meeting, held online on the 1st to 4th of September 2020. The meeting covered topics related to new methodologies to study aging, knowledge about basic mechanisms of longevity, latest interventional strategies to target the aging process as well as discussions about the impact of aging research on society and economy. More than 2000 participants and 65 speakers joined the meeting and we already look forward to an even larger meeting next year. Please mark your calendars for the 8th ARDD meeting that is scheduled for the 31st of August to 3rd of September, 2021, at Columbia University, USA

Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

Abstract The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared to information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known non-pathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification. This article is protected by copyright. All rights reserved.Peer reviewe

Deconstructing the therapeutic alliance: Reflections on the underlying dimensions of the concept. Clínica y Salud

Abstract. The concept of the alliance has received increasing attention from both clinicians and researchers over the past thirty years. Yet it remains only vaguely defined, and its role and effect in therapy continues to be controversial. The goal of this paper is to clarify the meaning of the concept as it is perceived by clients and therapists, and to compare and contrast these perceptions to the notion of the alliance as it is de-facto implemented in research through the most frequently used alliance measures. Our results indicate that clients and therapists pay attention to different aspects of the relationship when they assess the quality of the alliance. The most frequently used measures share some important features but also exhibit significant differences. Some alliance measures attempt to accommodate the differences in the clients&apos; and therapists&apos; points of view but others ignore them. In general, these popular measures do not appear to be closely matched to the unique client/therapist perspectives. The impact of the substantial variations between measures and the absence of a clear distinction between the differing perspectives of clients and therapists is discussed. Keywords: concept, therapeutic alliance, therapy. Resumen. El concepto de la alianza terapéutica ha sido objeto de una creciente atención por parte de terapeutas y investigadores en los últimos treinta años. No obstante, aún no se ha llegado a una definición precisa del mismo, y aún no existe consenso sobre su papel y efecto en la terapia. El objetivo de este artículo es clarificar el significado del concepto tal y como lo perciben clientes y terapeutas, y comparar y contrastar estas percepciones con la forma en que se implementa la alianza en la literatura científica a través de las medidas más frecuentes de la alianza. Nuestros resultados indican que, cuando evalúan la calidad de la alianza, los clientes y terapeutas se centran en aspectos diferentes de la relación. Las medidas más empleadas tienen algunas importantes características en común, pero también exhiben diferencias importantes. Algunas medidas de la alianza intentan tener en cuenta las diferencias entre los puntos de vista de clientes y terapeutas, pero otras no. En general, las medidas más populares no parecen adecuarse a las particulares perspectivas cliente/terapeuta. Se aborda el impacto de las variaciones importantes entre medidas, y de la ausencia de una distinción clara entre las perspectivas divergentes de clientes y terapeutas