scispace - formally typeset
Search or ask a question

Showing papers by "Hospital General Universitario Gregorio Marañón published in 2021"


Journal ArticleDOI
TL;DR: In this article, the authors conducted a systematic review with meta-analysis of birth cohort/cross-sectional/cohort studies, representative of the general population, reporting age at onset for any ICD/DSM-mental disorders identified in PubMed/Web of Science (up to 16/05/2020) (PROSPERO:CRD42019143015).
Abstract: Promotion of good mental health, prevention, and early intervention before/at the onset of mental disorders improve outcomes. However, the range and peak ages at onset for mental disorders are not fully established. To provide robust, global epidemiological estimates of age at onset for mental disorders, we conducted a PRISMA/MOOSE-compliant systematic review with meta-analysis of birth cohort/cross-sectional/cohort studies, representative of the general population, reporting age at onset for any ICD/DSM-mental disorders, identified in PubMed/Web of Science (up to 16/05/2020) (PROSPERO:CRD42019143015). Co-primary outcomes were the proportion of individuals with onset of mental disorders before age 14, 18, 25, and peak age at onset, for any mental disorder and across International Classification of Diseases 11 diagnostic blocks. Median age at onset of specific disorders was additionally investigated. Across 192 studies (n = 708,561) included, the proportion of individuals with onset of any mental disorders before the ages of 14, 18, 25 were 34.6%, 48.4%, 62.5%, and peak age was 14.5 years (k = 14, median = 18, interquartile range (IQR) = 11-34). For diagnostic blocks, the proportion of individuals with onset of disorder before the age of 14, 18, 25 and peak age were as follows: neurodevelopmental disorders: 61.5%, 83.2%, 95.8%, 5.5 years (k = 21, median=12, IQR = 7-16), anxiety/fear-related disorders: 38.1%, 51.8%, 73.3%, 5.5 years (k = 73, median = 17, IQR = 9-25), obsessive-compulsive/related disorders: 24.6%, 45.1%, 64.0%, 14.5 years (k = 20, median = 19, IQR = 14-29), feeding/eating disorders/problems: 15.8%, 48.1%, 82.4%, 15.5 years (k = 11, median = 18, IQR = 15-23), conditions specifically associated with stress disorders: 16.9%, 27.6%, 43.1%, 15.5 years (k = 16, median = 30, IQR = 17-48), substance use disorders/addictive behaviours: 2.9%, 15.2%, 48.8%, 19.5 years (k = 58, median = 25, IQR = 20-41), schizophrenia-spectrum disorders/primary psychotic states: 3%, 12.3%, 47.8%, 20.5 years (k = 36, median = 25, IQR = 20-34), personality disorders/related traits: 1.9%, 9.6%, 47.7%, 20.5 years (k = 6, median = 25, IQR = 20-33), and mood disorders: 2.5%, 11.5%, 34.5%, 20.5 years (k = 79, median = 31, IQR = 21-46). No significant difference emerged by sex, or definition of age of onset. Median age at onset for specific mental disorders mapped on a time continuum, from phobias/separation anxiety/autism spectrum disorder/attention deficit hyperactivity disorder/social anxiety (8-13 years) to anorexia nervosa/bulimia nervosa/obsessive-compulsive/binge eating/cannabis use disorders (17-22 years), followed by schizophrenia, personality, panic and alcohol use disorders (25-27 years), and finally post-traumatic/depressive/generalized anxiety/bipolar/acute and transient psychotic disorders (30-35 years), with overlap among groups and no significant clustering. These results inform the timing of good mental health promotion/preventive/early intervention, updating the current mental health system structured around a child/adult service schism at age 18.

537 citations


Journal ArticleDOI
TL;DR: Being chronically immunosuppressed, liver transplant patients have an increased risk of acquiring Covid-19 but their mortality rates are lower than matched general population, and complete immunOSuppression withdrawal should be discouraged.

244 citations


Journal ArticleDOI
TL;DR: A review of the existing literature on the effects of lockdown measures established as a response to the COVID-19 pandemic on the mental health of children and adolescents is presented in this paper.
Abstract: COVID-19 was declared a pandemic in March 2020, resulting in many countries worldwide calling for lockdowns. This study aimed to review the existing literature on the effects of the lockdown measures established as a response to the COVID-19 pandemic on the mental health of children and adolescents. Embase, Ovid, Global Health, PsycINFO, Web of Science, and pre-print databases were searched in this PRISMA-compliant systematic review (PROSPERO: CRD42021225604). We included individual studies reporting on a wide range of mental health outcomes, including risk and protective factors, conducted in children and adolescents (aged ≤ 19 years), exposed to COVID-19 lockdown. Data extraction and quality appraisal were conducted by independent researchers, and results were synthesised by core themes. 61 articles with 54,999 children and adolescents were included (mean age = 11.3 years, 49.7% female). Anxiety symptoms and depression symptoms were common in the included studies and ranged 1.8–49.5% and 2.2–63.8%, respectively. Irritability (range = 16.7–73.2%) and anger (range = 30.0–51.3%), were also frequently reported by children and adolescents. Special needs and the presence of mental disorders before the lockdown, alongside excessive media exposure, were significant risk factors for anxiety. Parent–child communication was protective for anxiety and depression. The COVID-19 lockdown has resulted in psychological distress and highlighted vulnerable groups such as those with previous or current mental health difficulties. Supporting the mental health needs of children and adolescents at risk is key. Clinical guidelines to alleviate the negative effects of COVID-19 lockdown and public health strategies to support this population need to be developed.

228 citations


Journal ArticleDOI
04 Jan 2021
TL;DR: In this article, the authors collected retrospective clinicopathological and PAM50 data from 3,689 patients with HER2-negative disease and made the following observations: the proportion of HER2low was higher in HR-positive disease (65.4%) than triple-negative BC (TNBC, 36.6%).
Abstract: Novel antibody-drug conjugates against HER2 are showing high activity in HER2-negative breast cancer (BC) with low HER2 expression (i.e., 1+ or 2+ and lack of ERBB2 amplification). However, the clinical and molecular features of HER2-low BC are yet to be elucidated. Here, we collected retrospective clinicopathological and PAM50 data from 3,689 patients with HER2-negative disease and made the following observations. First, the proportion of HER2-low was higher in HR-positive disease (65.4%) than triple-negative BC (TNBC, 36.6%). Second, within HR-positive disease, ERBB2 and luminal-related genes were more expressed in HER2-low than HER2 0. In contrast, no gene was found differentially expressed in TNBC according to HER2 expression. Third, within HER2-low, ERBB2 levels were higher in HR-positive disease than TNBC. Fourth, HER2-low was not associated with overall survival in HR-positive disease and TNBC. Finally, the reproducibility of HER2-low among pathologists was suboptimal. This study emphasizes the large biological heterogeneity of HER2-low BC, and the need to implement reproducible and sensitive assays to measure low HER2 expression.

192 citations


Journal ArticleDOI
TL;DR: PURPOSEBEACON CRC evaluated encorafenib plus cetuximab with or without binimetinib versus investigators' choice of irinotecan or FOLFIRI plus CetuxIMB in patients with BRAFV600E-mutant metastatic...
Abstract: PURPOSEBEACON CRC evaluated encorafenib plus cetuximab with or without binimetinib versus investigators' choice of irinotecan or FOLFIRI plus cetuximab in patients with BRAFV600E–mutant metastatic ...

188 citations


Journal ArticleDOI
TL;DR: In the phase III CheckMate 067 trial, durable clinical benefit was demonstrated previously with nivolumab plus ipilimumab and nivolaumab alone versus IPILimumab as discussed by the authors.
Abstract: PURPOSEIn the phase III CheckMate 067 trial, durable clinical benefit was demonstrated previously with nivolumab plus ipilimumab and nivolumab alone versus ipilimumab. Here, we report 6.5-year effi...

179 citations



Journal ArticleDOI
01 Feb 2021-Mycoses
TL;DR: This work describes eight CAPA patients, compares them to colonised ICU patients with coronavirus disease 2019 (COVID‐19), and reviews the published literature from Western countries.
Abstract: Objectives Information on the recently COVID-19-associated pulmonary aspergillosis (CAPA) entity is scarce. We describe eight CAPA patients, compare them to colonised ICU patients with coronavirus disease 2019 (COVID-19), and review the published literature from Western countries. Methods Prospective study (March to May, 2020) that included all COVID-19 patients admitted to a tertiary hospital. Modified AspICU and European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria were used. Results COVID-19-associated pulmonary aspergillosis was diagnosed in eight patients (3.3% of 239 ICU patients), mostly affected non-immunocompromised patients (75%) with severe acute respiratory distress syndrome (ARDS) receiving corticosteroids. Diagnosis was established after a median of 15 days under mechanical ventilation. Bronchoalveolar lavage was performed in two patients with positive Aspergillus fumigatus cultures and galactomannan (GM) index. Serum GM was positive in 4/8 (50%). Thoracic CT scan findings fulfilled EORTC/MSG criteria in one case. Isavuconazole was used in 4/8 cases. CAPA-related mortality was 100% (8/8). Compared with colonised patients, CAPA subjects were administered tocilizumab more often (100% vs. 40%, p = .04), underwent longer courses of antibacterial therapy (13 vs. 5 days, p = .008), and had a higher all-cause mortality (100% vs. 40%, p = .04). We reviewed 96 similar cases from recent publications: 59 probable CAPA (also putative according modified AspICU), 56 putative cases and 13 colonisations according AspICU algorithm; according EORTC/MSG six proven and two probable. Overall, mortality in the reviewed series was 56.3%. Conclusions COVID-19-associated pulmonary aspergillosis must be considered a serious and potentially life-threatening complication in patients with severe COVID-19 receiving immunosuppressive treatment.

144 citations


Journal ArticleDOI
TL;DR: The PALLAS trial as discussed by the authors investigated whether the addition of 2 years of palbociclib to adjuvant endocrine therapy improves invasive disease-free survival over endocrine treatment alone in patients with hormone-receptor-positive, HER2-negative, early stage breast cancer.
Abstract: Summary Background Palbociclib added to endocrine therapy improves progression-free survival in hormone-receptor-positive, HER2-negative, metastatic breast cancer. The PALLAS trial aimed to investigate whether the addition of 2 years of palbociclib to adjuvant endocrine therapy improves invasive disease-free survival over endocrine therapy alone in patients with hormone-receptor-positive, HER2-negative, early-stage breast cancer. Methods PALLAS is an ongoing multicentre, open-label, randomised, phase 3 study that enrolled patients at 406 cancer centres in 21 countries worldwide with stage II–III histologically confirmed hormone-receptor-positive, HER2-negative breast cancer, within 12 months of initial diagnosis. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance score of 0 or 1. Patients were randomly assigned (1:1) in permuted blocks of random size (4 or 6), stratified by anatomic stage, previous chemotherapy, age, and geographical region, by use of central telephone-based and web-based interactive response technology, to receive either 2 years of palbociclib (125 mg orally once daily on days 1–21 of a 28-day cycle) with ongoing standard provider or patient-choice adjuvant endocrine therapy (tamoxifen or aromatase inhibitor, with or without concurrent luteinising hormone-releasing hormone agonist), or endocrine therapy alone, without masking. The primary endpoint of the study was invasive disease-free survival in the intention-to-treat population. Safety was assessed in all randomly assigned patients who started palbociclib or endocrine therapy. This report presents results from the second pre-planned interim analysis triggered on Jan 9, 2020, when 67% of the total number of expected invasive disease-free survival events had been observed. The trial is registered with ClinicalTrials.gov (NCT02513394) and EudraCT (2014-005181-30). Findings Between Sept 1, 2015, and Nov 30, 2018, 5760 patients were randomly assigned to receive palbociclib plus endocrine therapy (n=2883) or endocrine therapy alone (n=2877). At the time of the planned second interim analysis, at a median follow-up of 23·7 months (IQR 16·9–29·2), 170 of 2883 patients assigned to palbociclib plus endocrine therapy and 181 of 2877 assigned to endocrine therapy alone had invasive disease-free survival events. 3-year invasive disease-free survival was 88·2% (95% CI 85·2–90·6) for palbociclib plus endocrine therapy and 88·5% (85·8–90·7) for endocrine therapy alone (hazard ratio 0·93 [95% CI 0·76–1·15]; log-rank p=0·51). As the test statistic comparing invasive disease-free survival between groups crossed the prespecified futility boundary, the independent data monitoring committee recommended discontinuation of palbociclib in patients still receiving palbociclib and endocrine therapy. The most common grade 3–4 adverse events were neutropenia (1742 [61·3%] of 2840 patients on palbociclib and endocrine therapy vs 11 [0·3%] of 2903 on endocrine therapy alone), leucopenia (857 [30·2%] vs three [0·1%]), and fatigue (60 [2·1%] vs ten [0·3%]). Serious adverse events occurred in 351 (12·4%) of 2840 patients on palbociclib plus endocrine therapy versus 220 (7·6%) of 2903 patients on endocrine therapy alone. There were no treatment-related deaths. Interpretation At the planned second interim analysis, addition of 2 years of adjuvant palbociclib to adjuvant endocrine therapy did not improve invasive disease-free survival compared with adjuvant endocrine therapy alone. On the basis of these findings, this regimen cannot be recommended in the adjuvant setting. Long-term follow-up of the PALLAS population and correlative studies are ongoing. Funding Pfizer.

143 citations


Journal ArticleDOI
Livio Pagano1, Livio Pagano2, Jon Salmanton-García3, Francesco Marchesi, Alessandro Busca, Paolo Corradini4, Martin Hoenigl5, Martin Hoenigl6, Nikolai Klimko, Philipp Koehler3, Antonio Pagliuca7, Francesco Passamonti8, Luisa Verga9, Benjamin Víšek, Osman Ilhan10, Gianpaolo Nadali, Barbora Weinbergerova11, Raúl Córdoba-Mascuñano, Monia Marchetti, Graham P. Collins12, Francesca Farina, Chiara Cattaneo, Alba Cabirta13, Maria Gomes-Silva, Federico Itri, Jaap van Doesum14, Marie-Pierre Ledoux, Martin Čerňan15, Ozren Jakšić, Rafael F. Duarte, Gabriele Magliano, Ali S. Omrani16, Nicola Stefano Fracchiolla17, Austin G. Kulasekararaj18, Austin G. Kulasekararaj7, Toni Valković19, Christian Bjørn Poulsen, Marina Machado20, Andreas Glenthøj, Igor Stoma21, Zdeněk Ráčil, Klára Piukovics22, Milan Navrátil, Ziad Emarah23, Uluhan Sili24, Johan Maertens25, Ola Blennow26, Rui Bergantim, Carolina García-Vidal, Lucia Prezioso, Anna Guidetti, Maria Ilaria Del Principe27, Marina Popova, Nick de Jonge28, Irati Ormazabal-Vélez, Noemí Fernández, Iker Falces-Romero29, Annarosa Cuccaro, Stef Meers, Caterina Buquicchio, Darko Antic30, Murtadha Al-Khabori31, Ramón García-Sanz32, Monika Biernat33, Maria Chiara Tisi, Ertan Sal3, Laman Rahimli3, Natasa Colovic30, Martin Schönlein34, Maria Calbacho, Carlo Tascini, Carolina Miranda-Castillo, Nina Khanna35, Gustavo-Adolfo Méndez, Verena Petzer36, Jan Novák, Caroline Besson, Rémy Duléry37, Sylvain Lamure38, Marcio Nucci39, Giovanni Zambrotta9, Pavel Žák, Guldane Cengiz Seval10, Valentina Bonuomo, Jiří Mayer11, Alberto López-García, Maria Vittoria Sacchi, Stephen Booth12, Fabio Ciceri, Margherita Oberti, Marco Salvini8, Macarena Izuzquiza13, Raquel Nunes-Rodrigues, Emanuele Ammatuna14, Aleš Obr15, Raoul Herbrecht, Lucía Núñez-Martín-Buitrago, Valentina Mancini, Hawraa M Shwaylia16, Mariarita Sciumè17, Jenna Essame7, Marietta Nygaard, Josip Batinić40, Josip Batinić41, Yung Gonzaga, Isabel Regalado-Artamendi20, Linda Katharina Karlsson, Maryia Shapetska, Michaela Hanakova, Shaimaa El-Ashwah23, Zita Borbényi22, Gökçe Melis Çolak24, Anna Nordlander26, Giulia Dragonetti1, Giulia Dragonetti2, Alessio Maria Edoardo Maraglino1, Alessio Maria Edoardo Maraglino2, Amelia Rinaldi, Cristina De Ramón-Sánchez32, Oliver A Cornely 
TL;DR: In this paper, the authors studied the risk factors for adverse outcomes in patients with hematological malignancies (HM) who developed COVID-19 and analyzed predictors of mortality.
Abstract: Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value < 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases. This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases.

141 citations


Journal ArticleDOI
Áine O'Toole1, Verity Hill1, Oliver G. Pybus2, Alexander Watts3, Issac I. Bogoch4, Issac I. Bogoch5, Kamran Khan5, Kamran Khan3, Jane P. Messina2, Houriiyah Tegally6, Richard R. Lessells6, Jennifer Giandhari6, Sureshnee Pillay6, Kefentse Arnold Tumedi, Gape Nyepetsi, Malebogo Kebabonye, Maitshwarelo Matsheka, Madisa Mine, Sima Tokajian7, Hamad Hassan8, Tamara Salloum7, Georgi Merhi7, Jad Koweyes7, Jemma L. Geoghegan9, Jemma L. Geoghegan10, Joep de Ligt10, Xiaoyun Ren10, Matthew Storey10, Nikki E. Freed11, Chitra Pattabiraman12, Pramada Prasad12, Anita Desai12, Ravi Vasanthapuram12, Thomas F. Schulz13, Lars Steinbrück13, Tanja Stadler14, Antonio Parisi, Angelica Bianco, Darío García de Viedma15, Sergio Buenestado-Serrano15, Vítor Borges16, Joana Isidro16, Sílvia Duarte16, João Paulo Gomes16, Neta S. Zuckerman17, Michal Mandelboim17, Orna Mor17, Torsten Seemann18, Alicia Arnott, Jenny Draper, Mailie Gall, William Rawlinson, Ira Deveson, Sanmarié Schlebusch19, Jamie McMahon19, Lex E. X. Leong, Chuan Kok Lim, Maria Chironna20, Daniela Loconsole20, Antonin Bal, Laurence Josset, Edward C. Holmes21, Kirsten St. George22, Erica Lasek-Nesselquist22, Reina S. Sikkema23, Bas B. Oude Munnink23, Marion Koopmans23, Mia Brytting24, V. Sudha rani25, S. Pavani25, Teemu Smura26, Albert Heim13, Satu Kurkela26, Massab Umair, Muhammad Salman, Barbara Bartolini, Martina Rueca, Christian Drosten27, Thorsten Wolff28, Olin K. Silander11, Dirk Eggink, Chantal Reusken, Harry Vennema, Aekyung Park, Christine V.F. Carrington29, Nikita Sahadeo29, Michael J. Carr30, Gabo Gonzalez30, Search Alliance San Diego, SeqCOVID-Spain, Tulio de Oliveira6, Nuno R. Faria31, Nuno R. Faria2, Andrew Rambaut1, Moritz U. G. Kraemer2 
19 May 2021
TL;DR: In this article, two genetically-distinct clusters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with mutations of biological concern were reported, one in the United Kingdom and one in South Africa.
Abstract: Late in 2020, two genetically-distinct clusters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with mutations of biological concern were reported, one in the United Kingdom and one in South Africa. Using a combination of data from routine surveillance, genomic sequencing and international travel we track the international dispersal of lineages B.1.1.7 and B.1.351 (variant 501Y-V2). We account for potential biases in genomic surveillance efforts by including passenger volumes from location of where the lineage was first reported, London and South Africa respectively. Using the software tool grinch (global report investigating novel coronavirus haplotypes), we track the international spread of lineages of concern with automated daily reports, Further, we have built a custom tracking website (cov-lineages.org/global_report.html) which hosts this daily report and will continue to include novel SARS-CoV-2 lineages of concern as they are detected.

Journal ArticleDOI
Jonel Trebicka1, Javier Romaní Fernández2, Mária Papp3, Paolo Caraceni4, Wim Laleman5, Carmine Gambino6, Ilaria Giovo, Frank Erhard Uschner1, Christian Jansen7, Cesar Jimenez8, Rajeshwar P. Mookerjee9, Thierry Gustot, Agustín Albillos10, Rafael Bañares11, Peter Jarcuska12, Christian J. Steib13, Thomas Reiberger14, Juan Acevedo, Pietro Gatti, Debbie L. Shawcross15, Stefan Zeuzem1, Alexander Zipprich16, Salvatore Piano6, Thomas Berg17, Tony Bruns18, Karen Vagner Danielsen19, Minneke J. Coenraad20, Manuela Merli, Rudolf E. Stauber21, Heinz Zoller22, Jose Presa Ramos, Cristina Solé2, Germán Soriano, Andrea De Gottardi23, Henning Grønbæk24, Faouzi Saliba25, Christian Trautwein18, Haluk Tarik Kani26, Sven Francque, Stephen D. Ryder27, Pierre Nahon28, Pierre Nahon29, Manuel Romero-Gómez, Hans Van Vlierberghe30, Claire Francoz29, Michael Manns31, Elisabet Garcia-Lopez, Manuel Tufoni4, Alex Amoros, Marco Pavesi, Cristina Sanchez, Michael Praktiknjo7, Anna Curto, Carla Pitarch, Antonella Putignano, Esau Moreno, William Bernal15, Ferran Aguilar, Joan Clària2, Paola Ponzo, Zsuzsanna Vitális3, Giacomo Zaccherini4, Boglarka Balogh3, Alexander L. Gerbes13, Victor Vargas8, Carlo Alessandria, Mauro Bernardi4, Pere Ginès2, Richard Moreau29, Paolo Angeli6, Rajiv Jalan9, Vicente Arroyo, Miriam Maschmeier32, David Semela33, Laure Elkrief, Ahmed Elsharkawy34, Tamas Tornai34, István Tornai3, István Altorjay3, Agnese Antognoli4, Maurizio Baldassarre4, Martina Gagliardi4, Eleonora Bertoli6, Sara Mareso6, Alessandra Brocca6, Daniela Campion, Giorgio Maria Saracco, Martina Rizzo, Jennifer Lehmann7, Alessandra Pohlmann7, Maximilian J. Brol7, Johannes Chang7, Robert Schierwagen1, Elsa Solà, Nesrine Amari, Miguel Á. Rodríguez10, Frederik Nevens5, Ana Clemente11, Martin Janicko12, Daniel Markwardt13, Mattias Mandorfer14, Christoph Welsch1, T.M. Welzel1, Emanuela Ciraci, Vish Patel15, Cristina Ripoll16, Adam Herber17, Paul Horn, Flemming Bendtsen19, Lise Lotte Gluud19, Jelte J Schaapman20, Oliviero Riggio, Florian Rainer21, Joerg Tobiasch Moritz22, Monica Mesquita, Edilmar Alvarado-Tapias, Osagie Akpata9, Luise Aamann24, Didier Samuel25, Sylvie Tresson25, Pavel Strnad18, Roland Amathieu29, Roland Amathieu28, Macarena Simón-Talero8, Francois Smits, Natalie Van den Ende5, Javier Martínez10, Rita Garcia11, Harald Rupprechter14, Cornelius Engelmann17, Osman Ozdogan26 
TL;DR: This study identified precipitants that are significantly associated with a distinct clinical course and prognosis of patients with AD and specific preventive and therapeutic strategies targeting these events may improve outcome in decompensated cirrhosis.

Journal ArticleDOI
TL;DR: Twenty-five per cent of patients requiring hospitalization for Covid-19 died, the risk being higher in patients older than 70 and with medical co-morbidities, such as impaired renal function and diabetes.

Journal ArticleDOI
02 Jun 2021-Leukemia
TL;DR: In this article, the authors report on 382 COVID-19 patients having undergone allogeneic or autologous hematopoietic cell transplantation (HCT) reported to the European Society for Blood and Marrow Transplantation (EBMT) or to the Spanish Group of Hematoietic Stem Cell Transplant (GETH).
Abstract: This study reports on 382 COVID-19 patients having undergone allogeneic (n = 236) or autologous (n = 146) hematopoietic cell transplantation (HCT) reported to the European Society for Blood and Marrow Transplantation (EBMT) or to the Spanish Group of Hematopoietic Stem Cell Transplantation (GETH). The median age was 54.1 years (1.0-80.3) for allogeneic, and 60.6 years (7.7-81.6) for autologous HCT patients. The median time from HCT to COVID-19 was 15.8 months (0.2-292.7) in allogeneic and 24.6 months (-0.9 to 350.3) in autologous recipients. 83.5% developed lower respiratory tract disease and 22.5% were admitted to an ICU. Overall survival at 6 weeks from diagnosis was 77.9% and 72.1% in allogeneic and autologous recipients, respectively. Children had a survival of 93.4%. In multivariate analysis, older age (p = 0.02), need for ICU (p < 0.0001) and moderate/high immunodeficiency index (p = 0.04) increased the risk while better performance status (p = 0.001) decreased the risk for mortality. Other factors such as underlying diagnosis, time from HCT, GVHD, or ongoing immunosuppression did not significantly impact overall survival. We conclude that HCT patients are at high risk of developing LRTD, require admission to ICU, and have increased mortality in COVID-19.

Journal ArticleDOI
TL;DR: In this paper, the conceptual foundations of preventive psychiatry, encompassing the public health, Gordon's, US Institute of Medicine, World Health Organization, and good mental health frameworks, and neurodevelopmentally-sensitive clinical staging models, are reviewed.

Journal ArticleDOI
TL;DR: COPD remains prevalent in Spain and frequently underdiagnosed, with significant social and clinical differences including living alone, previous respiratory diagnoses, more comorbidities measured with the Charlson index, greater BODE and COTE scores, cognitive impairment, and depression.
Abstract: Background: Two previous national epidemiological studies, IBERPOC in 1997 and EPISCAN in 2007, determined the COPD burden in Spain. Changes in demographics and exposure to risk factors demand the periodic update of COPD prevalence and its determinants. Methods: EPISCAN II aimed to estimate the prevalence of COPD in the general population aged 40 years or older in all 17 regions of Spain. A random population screening sample, requiring 600 participants per region performed a questionnaire plus post-bronchodilator (post-BD) spirometry. Results: A total of 12,825 subjects were initially contacted, and 9433 (73.6%) agreed to participate, of whom 9092 performed a valid spirometry. Baseline characteristics were: 52.6% women, mean ± SD age 60 ± 11 years, 19.8% current- and 34.2% former-smokers. The prevalence of COPD measured by post-BD fixed ratio FEV1/FVC < 0.7 was 11.8% (95% C.I. 11.2–12.5) with a high variability by region (2.4-fold). Prevalence was 14.6% (95% C.I. 13.5–15.7) in males and 9.4% (95% C.I. 8.6–10.2) in females; according to the lower limit of normal (LLN) was 6.0% (95% C.I. 5.5–6.5) overall, by sex being 7.1% (95% C.I. 6.4–8.0) in males and 4.9% (95% C.I. 4.3–5.6) in females. Underdiagnosis of COPD was 74.7%. Cases with COPD were a mean of seven years older, more frequently male, of lower attained education, and with more smokers than the non-COPD population (p < 0.001). However, the number of cigarettes and pack-years in non-COPD participants was substantial, as it was the reported use of e-cigarettes (7.0% vs. 5.5%) (p = 0.045). There were also significant social and clinical differences including living alone, previous respiratory diagnoses, more comorbidities measured with the Charlson index, greater BODE and COTE scores, cognitive impairment, and depression (all p < 0.001). Conclusions: COPD remains prevalent in Spain and frequently underdiagnosed.

Journal ArticleDOI
TL;DR: In this article, the authors conducted a multinational study to determine the prevalence of pulmonary aspergillosis in patients with COVID-19 in intensive care units (ICU) and investigate risk factors for CAPA as well as outcome.

Journal ArticleDOI
TL;DR: In this article, the authors examined the consistency and magnitude of transition risk to psychosis in individuals at CHR-P, and found that a lower proportion of female individuals (β = -0.04 to - 0.01) with an increase proportion (0.02-0.03) in short-limited intermittent and high-intermittent frequency (HIE) in high-risk individuals.
Abstract: Importance Estimating the current likelihood of transitioning from a clinical high risk for psychosis (CHR-P) to psychosis holds paramount importance for preventive care and applied research. Objective To quantitatively examine the consistency and magnitude of transition risk to psychosis in individuals at CHR-P. Data sources PubMed and Web of Science databases until November 1, 2020. Manual search of references from previous articles. Study selection Longitudinal studies reporting transition risks in individuals at CHR-P. Data extraction and synthesis Meta-analysis compliant with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines; independent data extraction, manually and through digitalization of Kaplan-Meier curves. Main outcome and measures Primary effect size was cumulative risk of transition to psychosis at 0.5, 1, 1.5, 2, 2.5, 3, 4, and more than 4 years' follow-up, estimated using the numbers of individuals at CHR-P transitioning to psychosis at each time point. These analyses were complemented by meta-analytical Kaplan-Meier curves and speed of transition to psychosis (hazard rate). Random-effects meta-analysis, between-study heterogeneity analysis, study quality assessment, and meta-regressions were conducted. Results A total of 130 studies and 9222 individuals at CHR-P were included. The mean (SD) age was 20.3 (4.4) years, and 5100 individuals (55.3%) were male. The cumulative transition risk was 0.09 (95% CI, 0.07-0.10; k = 37; n = 6485) at 0.5 years, 0.15 (95% CI, 0.13-0.16; k = 53; n = 7907) at 1 year, 0.20 (95% CI, 0.17-0.22; k = 30; n = 5488) at 1.5 years, 0.19 (95% CI, 0.17-0.22; k = 44; n = 7351) at 2 years, 0.25 (95% CI, 0.21-0.29; k = 19; n = 3114) at 2.5 years, 0.25 (95% CI, 0.22-0.29; k = 29; n = 4029) at 3 years, 0.27 (95% CI, 0.23-0.30; k = 16; n = 2926) at 4 years, and 0.28 (95% CI, 0.20-0.37; k = 14; n = 2301) at more than 4 years. The cumulative Kaplan-Meier transition risk was 0.08 (95% CI, 0.08-0.09; n = 4860) at 0.5 years, 0.14 (95% CI, 0.13-0.15; n = 3408) at 1 year, 0.17 (95% CI, 0.16-0.19; n = 2892) at 1.5 years, 0.20 (95% CI, 0.19-0.21; n = 2357) at 2 years, 0.25 (95% CI, 0.23-0.26; n = 1444) at 2.5 years, 0.27 (95% CI, 0.25-0.28; n = 1029) at 3 years, 0.28 (95% CI, 0.26-0.29; n = 808) at 3.5 years, 0.29 (95% CI, 0.27-0.30; n = 737) at 4 years, and 0.35 (95% CI, 0.32-0.38; n = 114) at 10 years. The hazard rate only plateaued at 4 years' follow-up. Meta-regressions showed that a lower proportion of female individuals (β = -0.02; 95% CI, -0.04 to -0.01) and a higher proportion of brief limited intermittent psychotic symptoms (β = 0.02; 95% CI, 0.01-0.03) were associated with an increase in transition risk. Heterogeneity across the studies was high (I2 range, 77.91% to 95.73%). Conclusions and relevance In this meta-analysis, 25% of individuals at CHR-P developed psychosis within 3 years. Transition risk continued increasing in the long term. Extended clinical monitoring and preventive care may be beneficial in this patient population.

Journal ArticleDOI
TL;DR: It is possible to detect and formulate a group-level prognosis in adolescents at risk for psychosis and Randomised controlled trials suggested that family interventions, cognitive remediation and fish oil supplementation may improve cognition, symptoms and functioning.
Abstract: BACKGROUND The clinical high-risk state for psychosis (CHR-P) paradigm has facilitated the implementation of psychosis prevention into clinical practice; however, advancements in adolescent CHR-P populations are less established. METHODS We performed a PRISMA/MOOSE-compliant systematic review of the Web of Science database, from inception until 7 October 2019, to identify original studies conducted in CHR-P children and adolescents (mean age <18 years). Findings were systematically appraised around core themes: detection, prognosis and intervention. We performed meta-analyses (employing Q statistics and I 2 test) regarding the proportion of CHR-P subgroups, the prevalence of baseline comorbid mental disorders, the risk of psychosis onset and the type of interventions received at baseline. Quality assessment and publication bias were also analysed. RESULTS Eighty-seven articles were included (n = 4,667 CHR-P individuals). Quality of studies ranged from 3.5 to 8 (median 5.5) on a modified Newcastle-Ottawa scale. Detection: Individuals were aged 15.6 ± 1.2 years (51.5% males), mostly (83%) presenting with attenuated positive psychotic symptoms. CHR-P psychometric accuracy improved when caregivers served as additional informants. Comorbid mood (46.4%) and anxiety (31.4%) disorders were highly prevalent. Functioning and cognition were impaired. Neurobiological studies were inconclusive. PROGNOSIS Risk for psychosis was 10.4% (95%CI: 5.8%-18.1%) at 6 months, 20% (95%CI: 15%-26%) at 12 months, 23% (95%CI: 18%-29%) at 24 months and 23.3% (95%CI: 17.3%-30.7%) at ≥36 months. INTERVENTIONS There was not enough evidence to recommend one specific treatment (including cognitive behavioural therapy) over the others (including control conditions) to prevent the transition to psychosis in this population. Randomised controlled trials suggested that family interventions, cognitive remediation and fish oil supplementation may improve cognition, symptoms and functioning. At baseline, 30% of CHR-P adolescents were prescribed antipsychotics and 60% received psychotherapy. CONCLUSIONS It is possible to detect and formulate a group-level prognosis in adolescents at risk for psychosis. Future interventional research is required.

Journal ArticleDOI
Áine O'Toole1, Verity Hill1, Oliver G. Pybus2, Alexander Watts3, Issac I. Bogoch4, Issac I. Bogoch5, Kamran Khan4, Kamran Khan3, Jane P. Messina2, Houriiyah Tegally6, Richard R. Lessells6, Jennifer Giandhari6, Sureshnee Pillay6, Kefentse Arnold Tumedi, Gape Nyepetsi, Malebogo Kebabonye, Maitshwarelo Matsheka, Madisa Mine, Sima Tokajian7, Hamad Hassan8, Tamara Salloum7, Georgi Merhi7, Jad Koweyes7, Jemma L. Geoghegan9, Jemma L. Geoghegan10, Joep de Ligt10, Xiaoyun Ren10, Matthew Storey10, Nikki E. Freed11, Chitra Pattabiraman12, Pramada Prasad12, Anita Desai12, Ravi Vasanthapuram12, Thomas F. Schulz13, Lars Steinbrück13, Tanja Stadler14, Antonio Parisi, Angelica Bianco, Darío García de Viedma15, Sergio Buenestado-Serrano15, Vítor Borges16, Joana Isidro16, Sílvia Duarte16, João Paulo Gomes16, Neta S. Zuckerman17, Michal Mandelboim17, Orna Mor17, Torsten Seemann18, Alicia Arnott, Jenny Draper, Mailie Gall, William D. Rawlinson, Ira Deveson, Sanmarié Schlebusch19, Jamie McMahon19, Lex E. X. Leong, Chuan Kok Lim, Maria Chironna20, Daniela Loconsole20, Antonin Bal, Laurence Josset, Edward C. Holmes21, Kirsten St. George22, Erica Lasek-Nesselquist22, Reina S. Sikkema23, Bas B. Oude Munnink23, Marion Koopmans23, Mia Brytting24, V. Sudha rani25, S. Pavani25, Teemu Smura26, Albert Heim13, Satu Kurkela26, Massab Umair, Muhammad Salman, Barbara Bartolini, Martina Rueca, Christian Drosten27, Thorsten Wolff28, Olin K. Silander11, Dirk Eggink, Chantal Reusken, Harry Vennema, Aekyung Park, Christine V.F. Carrington29, Nikita Sahadeo29, Michael J. Carr30, Gabo Gonzalez30, Search Alliance San Diego, SeqCOVID-Spain, Tulio de Oliveira6, Nuno R. Faria2, Nuno R. Faria31, Andrew Rambaut1, Moritz U. G. Kraemer2 
17 Sep 2021
TL;DR: In this article, two genetically-distinct clusters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with mutations of biological concern were reported, one in the United Kingdom and one in South Africa.
Abstract: Late in 2020, two genetically-distinct clusters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with mutations of biological concern were reported, one in the United Kingdom and one in South Africa. Using a combination of data from routine surveillance, genomic sequencing and international travel we track the international dispersal of lineages B.1.1.7 and B.1.351 (variant 501Y-V2). We account for potential biases in genomic surveillance efforts by including passenger volumes from location of where the lineage was first reported, London and South Africa respectively. Using the software tool grinch (global report investigating novel coronavirus haplotypes), we track the international spread of lineages of concern with automated daily reports, Further, we have built a custom tracking website (cov-lineages.org/global_report.html) which hosts this daily report and will continue to include novel SARS-CoV-2 lineages of concern as they are detected.

Journal ArticleDOI
TL;DR: This 6.5-y analysis represents the longest follow-up from a phase 3 melanoma trial in the modern checkpoint inhibitor combination therapy and targeted therapy era and shows durable improved outcomes with NIVO + IPI and NivO vs IPI in pts with advanced melanoma.
Abstract: 9506Background: In the phase 3 CheckMate 067 trial, a durable and sustained clinical benefit was achieved with nivolumab (NIVO) + ipilimumab (IPI) and NIVO alone vs IPI at 5-y of follow-up (overall...


Journal ArticleDOI
Ellie J. Coromilas1, Stephanie M. Kochav1, Isaac L Goldenthal1, Angelo B. Biviano1, Hasan Garan1, Seth Goldbarg2, Joon Hyuk Kim2, Ilhwan Yeo2, Cynthia M. Tracy3, Shant Ayanian3, Joseph G. Akar4, Avinainder Singh4, Shashank Jain4, Leandro Ioschpe Zimerman5, Mauricio Pimentel5, Stefan Osswald6, Raphael Twerenbold6, Nicolas Schaerli6, Lia Crotti7, Daniele Fabbri7, Gianfranco Parati7, Yi Li, Felipe Atienza8, Felipe Atienza9, Eduardo Zatarain8, Eduardo Zatarain9, Gary Tse10, Gary Tse11, Keith Sai Kit Leung12, Milton E Guevara-Valdivia13, Carlos A. Rivera-Santiago13, Kyoko Soejima14, Paolo De Filippo, Paola Ferrari, Giovanni Malanchini, Prapa Kanagaratnam15, Saud Ahmed Khawaja15, Ghada W. Mikhail15, Mauricio Scanavacca16, Ludhmila Abrahão Hajjar16, Brenno Rizerio16, Luciana Sacilotto16, Reza Mollazadeh17, Masoud Eslami17, Vahideh Laleh Far17, Anna Vittoria Mattioli18, Giuseppe Boriani18, Federico Migliore19, Alberto Cipriani19, Filippo Donato19, Paolo Compagnucci20, Michela Casella20, Antonio Dello Russo20, James Coromilas21, Andrew Aboyme21, Connor O'Brien22, Fatima Rodriguez23, Paul J. Wang23, Aditi Naniwadekar24, Melissa Y.Y. Moey24, Chia Siang Kow25, Wee Kooi Cheah26, Angelo Auricchio, Giulio Conte, Jongmin Hwang27, Seongwook Han27, Pietro Enea Lazzerini28, Federico Franchi28, Amato Santoro28, Pier Leopoldo Capecchi28, Jose A. Joglar29, Anna Rosenblatt29, Marco Zardini, Serena Bricoli, Rosario Bonura, Julio Echarte-Morales, Tomás Benito-González, Carlos Minguito-Carazo, Felipe Fernández-Vázquez, Elaine Wan1 

Journal ArticleDOI
TL;DR: Treatment with corticosteroid-cyclophosphamide induced remission in a significantly greater number of patients with primary membranous nephropathy than tacrolimus-rituximab, and serious adverse events were similar in both groups.

Journal ArticleDOI
TL;DR: The use of T1 mapping and application of the modified Lake Louise Criteria provides important diagnostic value, and T 1 mapping provides prognostic value in patients with ICI myocarditis.

Journal ArticleDOI
Isabelle Cleynen1, Worrawat Engchuan2, Matthew S. Hestand3, Matthew S. Hestand1, Matthew S. Hestand4, Tracy Heung5, Tracy Heung6, Aaron M. Holleman7, H. Richard Johnston7, Thomas Monfeuga8, Donna M. McDonald-McGinn9, Donna M. McDonald-McGinn10, Raquel E. Gur9, Bernice E. Morrow11, Ann Swillen1, Jacob A. S. Vorstman10, Jacob A. S. Vorstman12, Jacob A. S. Vorstman13, Carrie E. Bearden14, Eva W.C. Chow5, Eva W.C. Chow13, Marianne Bernadette van den Bree8, Beverly S. Emanuel10, Joris Vermeesch1, Stephen T. Warren7, Michael John Owen8, Pankaj Chopra7, David J. Cutler7, Richard Duncan7, Alex V. Kotlar7, Jennifer G. Mulle7, Anna J. Voss7, Michael E. Zwick7, Alexander Diacou11, Aaron Golden11, Tingwei Guo11, Jhih Rong Lin11, Tao Wang11, Zhengdong Zhang11, Yingjie Zhao11, Christian R. Marshall13, Daniele Merico2, Andrea Jin10, Brenna Lilley10, Harold I. Salmons10, Oanh Tran10, Peter Holmans8, Antonio F. Pardiñas8, James T.R. Walters8, Wolfram Demaerel1, Erik Boot6, Nancy J. Butcher5, Gregory A. Costain5, Gregory A. Costain15, Chelsea Lowther5, Rens Evers16, Therese van Amelsvoort16, Esther D.A. van Duin16, Claudia Vingerhoets16, Jeroen Breckpot1, Koen Devriendt1, Elfi Vergaelen1, Annick Vogels1, T. Blaine Crowley10, Daniel E. McGinn10, Edward Moss10, Robert J. Sharkus10, Marta Unolt10, Elaine H. Zackai9, Elaine H. Zackai10, Monica E. Calkins9, Robert Sean Gallagher9, Ruben C. Gur9, Sunny X. Tang9, Rosemarie Fritsch17, Claudia Ornstein17, Gabriela M. Repetto18, Elemi J. Breetvelt13, Sasja N. Duijff12, Ania Fiksinski12, Ania Fiksinski5, Hayley Moss8, Maria Niarchou8, Kieran C. Murphy19, Sarah E. Prasad19, Eileen Daly20, Maria Gudbrandsen20, Clodagh M. Murphy20, Declan G. Murphy20, Antonio Buzzanca21, Fabio Di Fabio21, Maria Cristina Digilio, Maria Pontillo22, Bruno Marino21, Stefano Vicari22, Karlene Coleman7, Joseph F. Cubells7, Opal Y. Ousley7, Miri Carmel23, Doron Gothelf24, Doron Gothelf23, Ehud Mekori-Domachevsky24, Ehud Mekori-Domachevsky23, Elena Michaelovsky23, Ronnie Weinberger24, Abraham Weizman23, Leila Kushan14, Maria Jalbrzikowski25, Marco Armando26, Stephan Eliez26, Corrado Sandini26, Maude Schneider26, Frédérique Béna27, Kevin M. Antshel28, Wanda Fremont29, Wendy R. Kates29, Raoul Belzeaux, Tiffany Busa, Nicole Philip30, Linda E. Campbell31, Kathryn McCabe32, Kathryn McCabe31, Stephen R. Hooper33, Kelly Schoch34, Vandana Shashi34, Tony J. Simon32, Flora Tassone32, Celso Arango35, David Fraguas35, Sixto García-Miñaur36, Jaume Morey-Canyelles, Jordi Rosell, Damià H. Suñer, Jasna Raventos-Simic, Michael P. Epstein7, Nigel Williams8, Anne S. Bassett5, Anne S. Bassett13, Anne S. Bassett6 
TL;DR: Findings suggest that in addition to the deletion conferring a greatly increased risk to schizophrenia, the risk is higher when the 22q11.2 deletion and common polygenic risk factors that contribute to schizophrenia in the general population are both present.
Abstract: Schizophrenia occurs in about one in four individuals with 22q11.2 deletion syndrome (22q11.2DS). The aim of this International Brain and Behavior 22q11.2DS Consortium (IBBC) study was to identify genetic factors that contribute to schizophrenia, in addition to the ~20-fold increased risk conveyed by the 22q11.2 deletion. Using whole-genome sequencing data from 519 unrelated individuals with 22q11.2DS, we conducted genome-wide comparisons of common and rare variants between those with schizophrenia and those with no psychotic disorder at age ≥25 years. Available microarray data enabled direct comparison of polygenic risk for schizophrenia between 22q11.2DS and independent population samples with no 22q11.2 deletion, with and without schizophrenia (total n = 35,182). Polygenic risk for schizophrenia within 22q11.2DS was significantly greater for those with schizophrenia (padj = 6.73 × 10−6). Novel reciprocal case–control comparisons between the 22q11.2DS and population-based cohorts showed that polygenic risk score was significantly greater in individuals with psychotic illness, regardless of the presence of the 22q11.2 deletion. Within the 22q11.2DS cohort, results of gene-set analyses showed some support for rare variants affecting synaptic genes. No common or rare variants within the 22q11.2 deletion region were significantly associated with schizophrenia. These findings suggest that in addition to the deletion conferring a greatly increased risk to schizophrenia, the risk is higher when the 22q11.2 deletion and common polygenic risk factors that contribute to schizophrenia in the general population are both present.

Journal ArticleDOI
TL;DR: The authors conducted a systematic synthesis of umbrella reviews, which are systematic reviews of meta-analyses of individual studies, by searching international databases from inception to January 1, 2021, and included umbrella reviews on nonpurely genetic risk or protective factors for any ICD/DSM mental disorders, applying an established classification of the credibility of the evidence: class I (convincing), class II (highly suggestive), class III (suggestive), class IV (weak).

Journal ArticleDOI
Oana Nicoară-Farcău1, Oana Nicoară-Farcău2, Guohong Han3, Marika Rudler4, Debora Angrisani2, Alberto Monescillo5, Ferran Torres6, Georgina Casanovas, Jaime Bosch2, Jaime Bosch7, Yong Lv3, Dominique Thabut4, Daiming Fan3, Virginia Hernández-Gea2, Juan Carlos García-Pagán2, Christophe Bureau, Juan G. Abraldes2, Frederik Nevens8, Karel Caca, Wim Laleman8, Beate Appenrodt9, Angelo Luca10, Jean-Pierre Vinel, Joachim Mössner, Marco Di Pascoli2, Alexander Zipprich11, Tilman Sauerbruch9, Francisco Martinez-Lagares, Luis Ruiz-del-Arbol, Angel Sierra5, Clemencia Guevara5, Elena Jimenez5, Jose Miguel Marrero5, Enrique Buceta, Juan Francisco Sanchez, Ana Castellot5, Monica Penate5, Ana Cruz5, Elena Peña, Bogdan Procopeț1, Álvaro Giráldez, Lucio Amitrano, Càndid Villanueva, Luis Ibáñez-Samaniego12, Gilberto Silva-Junior2, Javier Martínez13, Joan Genescà6, Jonel Trebicka, Elba Llop14, José María Palazón, José Castellote2, Susana G. Rodrigues7, Lise Lotte Gluud15, Carlos Noronha Ferreira, Rafael Ramis Barceló, Nuria Cañete6, Manuel Rodríguez, Arnulf Ferlitsch16, Jose Luis Mundi, Henning Grønbæk17, Manuel Hernández-Guerra, Romano Sassatelli, Alessandra Dell'Era, Marco Senzolo18, Manuel Romero-Gómez, Meritxell Casas6, Helena Masnou, Massimo Primignani, Aleksander Krag19, Jose Luis Calleja14, Christian Jansen9, Marie Angèle Robic, Irene Conejo6, María-Vega Catalina12, Agustín Albillos13, Edilmar Alvarado, Maria Anna Guardascione, Marcel Tanțău1, Luo Zuo4, Xuan Zhu20, Jianbo Zhao21, Hui Xue22, Zaibo Jiang23, Yuzheng Zhuge24, Chunqing Zhang25, Junhui Sun26, Pengxu Ding27, Weixin Ren28, Yingchun Li29, Kewei Zhang, Wenguang Zhang27, Chuangye He4, Jiawei Zhong21, Qifeng Peng22, Fuquan Ma23, Junyang Luo24, Ming Zhang25, Guangchuan Wang26, Minhuang Sun, Junjiao Dong27, Wei Bai3, Wengang Guo3, Qiuhe Wang3, Xulong Yuan3, Zhengyu Wang3, Tianlei Yu3, Bohan Luo3, Xiaomei Li3, Jie Yuan3, Na Han3, Ying Zhu3, Jing Niu3, Kai Li3, Zhanxin Yin3, Yongzhan Nie3, P Fischer1, Horia Ștefănescu1, Andreea Pop1, Stig Borbjerg Laursen19, Fanny Turon2, Anna Baiges2, José Ferrusquía-Acosta2, Marta Magaz2, Eira Cerda2, Luis Téllez2, Giulia Allegretti2, Guilherme Macedo, David Haldrup17, Patricia M. Santos, Miguel Moura, Daniela Reis, Liliane Meireles, Patricia Sousa, Paula Alexandrino, Carmen A. Navascués, Salvador Augustin6, Vincenzo La Mura, Rafael Bañares12, Raquel Diaz12, Marta Gómez14, Cristina Ripoll11 
TL;DR: A meta-analysis of data from 1327 patients with cirrhosis, acute variceal bleeding, and Child-Pugh score between 10-13 points or CP-B+AB found that preemptive TIPS increased the proportion who survived for 1 year, in both subgroups separately, compared with drugs plus endoscopy.

Journal ArticleDOI
TL;DR: An SPL analysis system for wide-field images using deep convolutional neural networks (DCNNs) and a new method to extract intrapatient lesion saliency (ugly duckling criteria) on the basis of DCNN features from detected lesions are presented.
Abstract: A reported 96,480 people were diagnosed with melanoma in the United States in 2019, leading to 7230 reported deaths. Early-stage identification of suspicious pigmented lesions (SPLs) in primary care settings can lead to improved melanoma prognosis and a possible 20-fold reduction in treatment cost. Despite this clinical and economic value, efficient tools for SPL detection are mostly absent. To bridge this gap, we developed an SPL analysis system for wide-field images using deep convolutional neural networks (DCNNs) and applied it to a 38,283 dermatological dataset collected from 133 patients and publicly available images. These images were obtained from a variety of consumer-grade cameras (15,244 nondermoscopy) and classified by three board-certified dermatologists. Our system achieved more than 90.3% sensitivity (95% confidence interval, 90 to 90.6) and 89.9% specificity (89.6 to 90.2%) in distinguishing SPLs from nonsuspicious lesions, skin, and complex backgrounds, avoiding the need for cumbersome individual lesion imaging. We also present a new method to extract intrapatient lesion saliency (ugly duckling criteria) on the basis of DCNN features from detected lesions. This saliency ranking was validated against three board-certified dermatologists using a set of 135 individual wide-field images from 68 dermatological patients not included in the DCNN training set, exhibiting 82.96% (67.88 to 88.26%) agreement with at least one of the top three lesions in the dermatological consensus ranking. This method could allow for rapid and accurate assessments of pigmented lesion suspiciousness within a primary care visit and could enable improved patient triaging, utilization of resources, and earlier treatment of melanoma.

Journal ArticleDOI
TL;DR: In this paper, the authors provide an updated synthesis of evidence on the consistency and magnitude of neurocognitive functioning in individuals at clinical high risk for psychosis (CHR-P) and provide significant effects for age and education on processing speed.
Abstract: Importance Neurocognitive functioning is a potential biomarker to advance detection, prognosis, and preventive care for individuals at clinical high risk for psychosis (CHR-P). The current consistency and magnitude of neurocognitive functioning in individuals at CHR-P are undetermined. Objective To provide an updated synthesis of evidence on the consistency and magnitude of neurocognitive functioning in individuals at CHR-P. Data Sources Web of Science database, Cochrane Central Register of Reviews, and Ovid/PsycINFO and trial registries up to July 1, 2020. Study Selection Multistep literature search compliant with Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology performed by independent researchers to identify original studies reporting on neurocognitive functioning in individuals at CHR-P. Data Extraction and Synthesis Independent researchers extracted the data, clustering the neurocognitive tasks according to 7 Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) domains and 8 CHR-P domains. Random-effect model meta-analyses, assessment of publication biases and study quality, and meta-regressions were conducted. Main Outcomes and Measures The primary effect size measure was Hedgesgof neurocognitive functioning in individuals at CHR-P (1) compared with healthy control (HC) individuals or (2) compared with individuals with first-episode psychosis (FEP) or (3) stratified for the longitudinal transition to psychosis. Results A total of 78 independent studies were included, consisting of 5162 individuals at CHR-P (mean [SD; range] age, 20.2 [3.3; 12.0-29.0] years; 2529 [49.0%] were female), 2865 HC individuals (mean [SD; range] age, 21.1 [3.6; 12.6-29.2] years; 1490 [52.0%] were female), and 486 individuals with FEP (mean [SD; range] age, 23.0 [2.0; 19.1-26.4] years; 267 [55.9%] were female). Compared with HC individuals, individuals at CHR-P showed medium to large deficits on the Stroop color word reading task (g = −1.17; 95% CI, −1.86 to −0.48), Hopkins Verbal Learning Test–Revised (g = −0.86; 95% CI, −1.43 to −0.28), digit symbol coding test (g = −0.74; 95% CI, −1.19 to −0.29), Brief Assessment of Cognition Scale Symbol Coding (g = −0.67; 95% CI, −0.95 to −0.39), University of Pennsylvania Smell Identification Test (g = −0.55; 95% CI, −0.97 to −0.12), Hinting Task (g = −0.53; 95% CI, −0.77 to −0.28), Rey Auditory Verbal Learning Test (g = −0.50; 95% CI, −0.78 to −0.21), California Verbal Learning Test (CVLT) (g = −0.50; 95% CI, −0.64 to −0.36), and National Adult Reading Test (g = −0.52; 95% CI, −1.01 to −0.03). Individuals at CHR-P were less impaired than individuals with FEP. Longitudinal transition to psychosis from a CHR-P state was associated with medium to large deficits in the CVLT task (g = −0.58; 95% CI, −1.12 to −0.05). Meta-regressions found significant effects for age and education on processing speed. Conclusions and Relevance Findings from this meta-analysis support neurocognitive dysfunction as a potential detection and prognostic biomarker in individuals at CHR-P. These findings may advance clinical research and inform preventive approaches.