Showing papers by "Hospital General Universitario Gregorio Marañón published in 2021"
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University of Padua1, King's College London2, Karolinska Institutet3, University of Ferrara4, University of Pavia5, Hospital General Universitario Gregorio Marañón6, Yonsei University7, University College London8, National Health Service9, University of Cambridge10, Deakin University11, University of Toronto12
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
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University of Barcelona1, Hospital General Universitario Gregorio Marañón2, Autonomous University of Madrid3, University of the Basque Country4, University of Navarra5, Autonomous University of Barcelona6, Instituto Politécnico Nacional7, Hospital Universitario La Paz8, Organización Nacional de Trasplantes9
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
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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
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University of Naples Federico II1, The Breast Cancer Research Foundation2, University of Barcelona3, University of Genoa4, University of North Carolina at Chapel Hill5, University of Valencia6, Università Campus Bio-Medico7, Hebron University8, Pontifícia Universidade Católica do Rio Grande do Sul9, Hospital General Universitario Gregorio Marañón10
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
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Hebron University1, Katholieke Universiteit Leuven2, Memorial Sloan Kettering Cancer Center3, Imperial College London4, Peter MacCallum Cancer Centre5, Asan Medical Center6, Netherlands Cancer Institute7, Oslo University Hospital8, Sarah Cannon Research Institute9, Hospital General Universitario Gregorio Marañón10, Pfizer11, University of Texas MD Anderson Cancer Center12
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
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Memorial Sloan Kettering Cancer Center1, University of Colorado Boulder2, Aix-Marseille University3, University of Michigan4, Texas Oncology5, Swansea University6, European Institute of Oncology7, Cross Cancer Institute8, Princess Margaret Cancer Centre9, Hospital General Universitario Gregorio Marañón10, Netherlands Cancer Institute11, Katholieke Universiteit Leuven12, University of Sydney13, University of Paris14, Peter MacCallum Cancer Centre15, University of California, San Diego16, Bristol-Myers Squibb17, The Royal Marsden NHS Foundation Trust18, Harvard University19
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
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TL;DR: The nationwide experience with solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients diagnosed with coronavirus disease 2019 (COVID‐19) in Spain until 13 July 2020 is reported.
152 citations
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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
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Harvard University1, Mayo Clinic2, Hospital General Universitario Gregorio Marañón3, Indiana University4, Medical University of Vienna5, Regions Hospital6, University of Texas MD Anderson Cancer Center7, The Royal Marsden NHS Foundation Trust8, Memorial Sloan Kettering Cancer Center9, Hollywood Private Hospital10, University of California, San Francisco11, Laval University12, Missouri Baptist Medical Center13, University of A Coruña14, Johns Hopkins University15, University Hospital of Basel16, Innsbruck Medical University17, Orlando Health18, Breast International Group19, Pfizer20, University of Pennsylvania21
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
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Agostino Gemelli University Polyclinic1, Catholic University of the Sacred Heart2, University of Cologne3, University of Milan4, University of California, San Diego5, Medical University of Graz6, University of Cambridge7, University of Insubria8, University of Milano-Bicocca9, Ankara University10, Masaryk University11, Churchill Hospital12, Autonomous University of Barcelona13, University Medical Center Groningen14, Palacký University, Olomouc15, Hamad Medical Corporation16, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico17, King's College London18, University of Rijeka19, Hospital General Universitario Gregorio Marañón20, Gomel State Medical University21, University of Szeged22, Mansoura University23, Marmara University24, Katholieke Universiteit Leuven25, Karolinska University Hospital26, University of Rome Tor Vergata27, Vanderbilt University Medical Center28, Hospital Universitario La Paz29, University of Belgrade30, Sultan Qaboos University31, Spanish National Research Council32, Wrocław Medical University33, University of Hamburg34, University Hospital of Basel35, Innsbruck Medical University36, Paris-Sorbonne University37, University of Montpellier38, Federal University of Rio de Janeiro39, University Hospital Centre Zagreb40, University of Zagreb41
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
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University of Edinburgh1, University of Oxford2, St. Michael's Hospital3, University Health Network4, University of Toronto5, University of KwaZulu-Natal6, Lebanese American University7, Lebanese University8, University of Otago9, Wellington Management Company10, Massey University11, National Institute of Mental Health and Neurosciences12, Hannover Medical School13, ETH Zurich14, Hospital General Universitario Gregorio Marañón15, Intelligence and National Security Alliance16, Israel Ministry of Health17, University of Melbourne18, Queensland Health19, University of Bari20, University of Sydney21, New York State Department of Health22, Erasmus University Rotterdam23, Public Health Agency of Sweden24, Osmania Medical College25, University of Helsinki26, Charité27, Robert Koch Institute28, University of the West Indies29, University College Dublin30, Imperial College London31
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.
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Goethe University Frankfurt1, University of Barcelona2, University of Debrecen3, University of Bologna4, Katholieke Universiteit Leuven5, University of Padua6, University Hospital Bonn7, Autonomous University of Barcelona8, Royal Free Hospital9, University of Alcalá10, Hospital General Universitario Gregorio Marañón11, University of Pavol Jozef Šafárik12, Ludwig Maximilian University of Munich13, Medical University of Vienna14, University of Cambridge15, Wittenberg University16, Leipzig University17, RWTH Aachen University18, University of Copenhagen19, Leiden University Medical Center20, Medical University of Graz21, Innsbruck Medical University22, University of Lugano23, Aarhus University Hospital24, Université Paris-Saclay25, Marmara University26, Nottingham University Hospitals NHS Trust27, French Institute of Health and Medical Research28, University of Paris29, Ghent University Hospital30, Hannover Medical School31, University of Münster32, University of Basel33, University of Birmingham34
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.
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University of Barcelona1, University of Milan2, Karolinska University Hospital3, Complutense University of Madrid4, Autonomous University of Madrid5, Hospital General Universitario Gregorio Marañón6, Katholieke Universiteit Leuven7, University of Liège8, University of Navarra9, Ghent University10, Erasmus University Rotterdam11, University of Bologna12, University of Milano-Bicocca13
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.
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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.
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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.
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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.
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Medical University of Graz1, BioTechMed-Graz2, Katholieke Universiteit Leuven3, University of Genoa4, University of Cologne5, Ludwig Maximilian University of Munich6, Hospital General Universitario Gregorio Marañón7, Aga Khan University8, Paracelsus Private Medical University of Salzburg9, University of Manchester10, University of California, San Diego11, University of Michigan12, University of Paris13, University Hospital of Wales14, University of São Paulo15, Vanderbilt University16, Innsbruck Medical University17
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.
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King's College London1, Hospital General Universitario Gregorio Marañón2, Karolinska Institutet3, University of Pavia4, Sapienza University of Rome5, University of Barcelona6, University of the Basque Country7, Yonsei University8, University of Padua9, South London and Maudsley NHS Foundation Trust10
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.
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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.
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University of Edinburgh1, University of Oxford2, St. Michael's Hospital3, University of Toronto4, University Health Network5, University of KwaZulu-Natal6, Lebanese American University7, Lebanese University8, University of Otago9, Wellington Management Company10, Massey University11, National Institute of Mental Health and Neurosciences12, Hannover Medical School13, ETH Zurich14, Hospital General Universitario Gregorio Marañón15, Intelligence and National Security Alliance16, Israel Ministry of Health17, University of Melbourne18, Queensland Health19, University of Bari20, University of Sydney21, New York State Department of Health22, Erasmus University Rotterdam23, Public Health Agency of Sweden24, Osmania Medical College25, University of Helsinki26, Charité27, Robert Koch Institute28, University of the West Indies29, University College Dublin30, Imperial College London31
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.
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Memorial Sloan Kettering Cancer Center1, University of Colorado Boulder2, Aix-Marseille University3, Curie Institute4, University of Michigan5, Texas Oncology6, Swansea University7, European Institute of Oncology8, Cross Cancer Institute9, Princess Margaret Cancer Centre10, Hospital General Universitario Gregorio Marañón11, Netherlands Cancer Institute12, Bristol-Myers Squibb13, The Royal Marsden NHS Foundation Trust14, Harvard University15
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...
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Kindai University1, Hospital General Universitario Gregorio Marañón2, Humanitas University3, University of Navarra4, CEU San Pablo University5, University of Southern California6, Kurume University7, Emory University8, Yokohama City University Medical Center9, Kyoto Prefectural University of Medicine10, University of Michigan11, Bristol-Myers Squibb12
TL;DR: In this paper, a phase I/II, open-label, non-comparative, multicentre trial (27 centres) included patients with Child-Pugh B (B7-B8) aHCC who received intravenous nivolumab 240 mg every 2 weeks until unacceptable toxicity or disease progression.
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Columbia University1, Cornell University2, George Washington University3, Yale University4, Universidade Federal do Rio Grande do Sul5, University Hospital of Basel6, University of Milano-Bicocca7, Hospital General Universitario Gregorio Marañón8, Carlos III Health Institute9, Tianjin Medical University10, Hospital Authority11, Aston University12, Mexican Social Security Institute13, Kyorin University14, Imperial College Healthcare15, University of São Paulo16, Tehran University of Medical Sciences17, University of Modena and Reggio Emilia18, University of Padua19, Marche Polytechnic University20, Rutgers University21, University of California, San Francisco22, Stanford University23, East Carolina University24, International Medical University25, Taiping Hospital26, Keimyung University27, University of Siena28, University of Texas Southwestern Medical Center29
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Radboud University Nijmegen1, Centre national de la recherche scientifique2, Autonomous University of Barcelona3, Hospital General Universitario Gregorio Marañón4, University of Barcelona5, Hospital Clínico San Carlos6, Hospital Universitario La Paz7, University of Paris8, French Institute of Health and Medical Research9, Complutense University of Madrid10
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.
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Toronto General Hospital1, Albert Einstein College of Medicine2, Harvard University3, Cornell University4, McGill University5, Brigham and Women's Hospital6, Aix-Marseille University7, University of Erlangen-Nuremberg8, Georgetown University9, Memorial Sloan Kettering Cancer Center10, Lehigh Valley Hospital11, Mount Sinai Hospital12, Hospital General Universitario Gregorio Marañón13, University of Southampton14, Lahey Hospital & Medical Center15, University of Navarra16, State University of Campinas17, National Institutes of Health18, University Health Network19, University of California, Los Angeles20, Imperial College London21, University of Pennsylvania22
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.
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Katholieke Universiteit Leuven1, The Centre for Applied Genomics2, University of Cincinnati3, Cincinnati Children's Hospital Medical Center4, Centre for Addiction and Mental Health5, University Health Network6, Emory University7, Cardiff University8, University of Pennsylvania9, Children's Hospital of Philadelphia10, Albert Einstein College of Medicine11, Utrecht University12, University of Toronto13, Semel Institute for Neuroscience and Human Behavior14, Hospital for Sick Children15, Maastricht University16, University of Chile17, Universidad del Desarrollo18, Royal College of Surgeons in Ireland19, King's College London20, Sapienza University of Rome21, Boston Children's Hospital22, Tel Aviv University23, Sheba Medical Center24, University of Pittsburgh25, University of Geneva26, Geneva College27, Syracuse University28, State University of New York Upstate Medical University29, Aix-Marseille University30, University of Newcastle31, University of California, Davis32, University of North Carolina at Chapel Hill33, Duke University34, Hospital General Universitario Gregorio Marañón35, Hospital Universitario La Paz36
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.
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Complutense University of Madrid1, Hospital General Universitario Gregorio Marañón2, Linköping University3, King's College London4, University of Ottawa5, University of Padua6, University of Freiburg7, National Health Service8, University of Cambridge9, Centre for Addiction and Mental Health10, Deakin University11, Icahn School of Medicine at Mount Sinai12, Yonsei University13, Boston Children's Hospital14, Oslo University Hospital15, South London and Maudsley NHS Foundation Trust16, University of Pavia17
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).
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Iuliu Hațieganu University of Medicine and Pharmacy1, University of Barcelona2, Fourth Military Medical University3, University of Paris4, Hospital Universitario Insular de Gran Canaria5, Autonomous University of Barcelona6, University of Bern7, Katholieke Universiteit Leuven8, University of Bonn9, ISMETT10, Martin Luther University of Halle-Wittenberg11, Hospital General Universitario Gregorio Marañón12, University of Alcalá13, Autonomous University of Madrid14, University of Copenhagen15, St John of God Health Care16, Aarhus University Hospital17, University of Padua18, Odense University Hospital19, Nanchang University20, Southern Medical University21, Xi'an Jiaotong University22, Sun Yat-sen University23, Nanjing University24, Shandong University25, Zhejiang University26, Zhengzhou University27, First Affiliated Hospital of Xinjiang Medical University28, Kunming Medical University29
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.
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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.
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Complutense University of Madrid1, King's College London2, Hospital General Universitario Gregorio Marañón3, University of Pavia4, Karolinska Institutet5, National Health Service6, National Institute for Health Research7, Massachusetts Department of Mental Health8, Beth Israel Deaconess Medical Center9
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.