A Delphi-method-based consensus guideline for definition of treatment-resistant depression for clinical trials

Criteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if conducted for regulatory purposes. We reviewed the literature and brought together a group of international experts (including clinicians, academics, researchers, employees of pharmaceutical companies, regulatory bodies representatives, and one person with lived experience) to evaluate the state-of-the-art and main controversies regarding the current classification. We then provided recommendations on how to design clinical trials, and on how to guide research in unmet needs and knowledge gaps. This report will feed into one of the main objectives of the EUropean Patient-cEntric clinicAl tRial pLatforms, Innovative Medicines Initiative (EU-PEARL, IMI) MDD project, to design a protocol for platform trials of new medications for TRD/PRD. © 2021, The Author(s).EU/EFPIA/Innovative Medicines Initiative 2 Joint Undertaking

Global Retinoblastoma Presentation and Analysis by National Income Level

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4) were female. Most patients (n = 3685 84.7%) were from low-and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 62.8%), followed by strabismus (n = 429 10.2%) and proptosis (n = 309 7.4%). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 95% CI, 12.94-24.80, and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 95% CI, 4.30-7.68). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs. © 2020 American Medical Association. All rights reserved

Funil de haines modificado: curvas de retenção de solos próximos à saturação Modified haines' funnel: soil water retention curves of soil samples near saturation

O movimento da água através da matriz do solo é geralmente modelado pelas equações de Darcy, Darcy-Buckingam e Richards, cujo uso está baseado no conhecimento de algumas propriedades físicas do solo, como, por exemplo, a distribuição de poros e a retenção de água pelo solo. A retenção de água pelo solo é conhecida a partir da determinação de sua curva de retenção (CR) ou curva característica. O primeiro objetivo deste trabalho foi apresentar um aparato simples, desenvolvido pela modificação do funil de placa porosa (funil de Haines), para a investigação e o levantamento de CRs detalhadas, em amostras de solos em condições de umidade próximas à saturação e em amostras com potenciais mátricos (&#968;m) que vão desde 0 kPa a aproximadamente -12 kPa (120 cm de altura de coluna de água). Foram investigados agregados de um Latossolo Vermelho distrófico (LVd) de uma região do Estado do Paraná, cujos diâmetros médios e densidades variaram, respectivamente, entre 1,6 e 5,7 cm e 1,01 e 1,31 g cm-3, e amostras arenosas reconstituídas com areias de diâmetros médios entre 0,106 mm e 2,000 mm, com dimensões fractais de fracionamento (Df) entre 2,5 e 3,0. O segundo objetivo do trabalho foi inferir a distribuição de poros das amostras investigadas. Isso foi conseguido utilizando-se os parâmetros de ajuste da curva de van Genuchtenaos pontos das CRs obtidas para a determinação da Função Capacidade de Água (FCA). Pela análise dessas FCAs, observou-se que as amostras de agregados de solo apresentaram um sistema poroso de maior complexidade; e que a variação da granulometria do solo arenoso está diretamente relacionada às modificações de suas propriedades de retenção de água. Finalmente, a variação na densidade dos agregados investigados não alterou significativamente o comportamento das curvas de retenção na faixa de tensões estudadas.<br>Water movement through the soil matrix is generally modeled using equations of Darcy, Darcy-Buckingham and Richards, which are based on the knowledge of some soil physical properties such as, soil pore size distribution and water retention characteristics. Soil water retention is determined by the soil water retention curve (SWRC) of the soil. The first objective of this study is to develop a simple apparatus by a modification of the Haines' funnel, to obtain detailed SWRC of near-saturation soil samples, samples in matric potentials (&#968;m) varying from 0 to -12 kPa (water column 120 cm). Soil aggregates of a Dystrophic Red Latosol (LVd) from Paraná were investigated, with an average diameter between 1.6 and 5.7 cm, soil bulk density between 1.01 and 1.31 g cm-3, respectively, and reconstituted sand samples, with a mean sand size of 0.106 µm to 2.000 mm, with fractal fragmentation dimensions (Df) varying from 2.5 to 3.0. A second objective was to analyze the soil pore size distribution of the soil samples. For this purpose the van Genuchten interpolation equation parameters were used to establish the water storage function (WSF) of the samples. In conclusion, an analysis of the WSFs showed that the soil aggregates had a more complex soil pore system; that the soil particle distribution of the sandy soil is directly related to their water retention properties; and finally, that bulk density did not significantly affect soil water retention of the soil aggregates

Flare-CME Models: An Observational Perspective (Invited Review)

International audienc