Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial.

There is no specific antiviral therapy recommended for coronavirus disease 2019 (COVID-19). In vitro studies indicate that the antiviral effect of chloroquine diphosphate (CQ) requires a high concentration of the drug.To evaluate the safety and efficacy of 2 CQ dosages in patients with severe COVID-19. This parallel, double-masked, randomized, phase IIb clinical trial with 81 adult patients who were hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was conducted from March 23 to April 5, 2020, at a tertiary care facility in Manaus, Brazilian Amazon. - Patients were allocated to receive high-dosage CQ (ie, 600 mg CQ twice daily for 10 days) or low-dosage CQ (ie, 450 mg twice daily on day 1 and once daily for 4 days). - Label: Main Outcomes and Measures Primary outcome was reduction in lethality by at least 50% in the high-dosage group compared with the low-dosage group. Data presented here refer primarily to safety and lethality outcomes during treatment on day 13. Secondary end points included participant clinical status, laboratory examinations, and electrocardiogram results. Outcomes will be presented to day 28. Viral respiratory secretion RNA detection was performed on days 0 and 4. Out of a predefined sample size of 440 patients, 81 were enrolled (41 [50.6%] to high-dosage group and 40 [49.4%] to low-dosage group). Enrolled patients had a mean (SD) age of 51.1 (13.9) years, and most (60 [75.3%]) were men. Older age (mean [SD] age, 54.7 [13.7] years vs 47.4 [13.3] years) and more heart disease (5 of 28 [17.9%] vs 0) were seen in the high-dose group. Viral RNA was detected in 31 of 40 (77.5%) and 31 of 41 (75.6%) patients in the low-dosage and high-dosage groups, respectively. Lethality until day 13 was 39.0% in the high-dosage group (16 of 41) and 15.0% in the low-dosage group (6 of 40). The high-dosage group presented more instance of QTc interval greater than 500 milliseconds (7 of 37 [18.9%]) compared with the low-dosage group (4 of 36 [11.1%]). Respiratory secretion at day 4 was negative in only 6 of 27 patients (22.2%). - Label: Conclusions and Relevance The preliminary findings of this study suggest that the higher CQ dosage should not be recommended for critically ill patients with COVID-19 because of its potential safety hazards, especially when taken concurrently with azithromycin and oseltamivir. These findings cannot be extrapolated to patients with nonsevere COVID-19

Avaliação da eficácia da psicoterapia on-line versus presencial no tratamento de transtornos de humor

Na intricada teia dos transtornos do humor, onde milhões enfrentam desafios globais, a depressão e o transtorno bipolar se destacam, demandando compreensão profunda e estratégias personalizadas. A persistente tristeza e os episódios extremos de humor, permeados por fatores externos, tornam o diagnóstico e tratamento essenciais, reverberando não só no indivíduo, mas nas redes sociais. Psicoterapia, presencial ou on-line, emerge como um componente crucial, oferecendo um espaço seguro e conveniência. Trata-se de uma pesquisa cujo estudo foi objetivo avaliar a avaliação da eficácia das psicoterapias on-line e presencial no tratamento de transtornos de humor. Para isso, se realizou uma revisão sistemática de literatura utilizando as bases de dados Medical Literature Analysis and Retrieval System On-line (MEDLINE), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) e Scientific Electronic Library On-line (SCIELO). Após análise e interpretação qualitativa dos resultados, concluiu-se que a psicoterapia on-line, especialmente a Terapia Cognitivo-Comportamental online (eTCC), apresentou maior eficácia no tratamento de transtornos de humor, enfatizando a ansiedade, em comparação com abordagens presenciais. A evidência consistente de uma redução nos sintomas ansiosos em diversos grupos de pacientes e condições clínicas ressaltou os benefícios dessa modalidade, incluindo a redução de custos sociais e econômicos, maior alcance clínico e melhorias globais nos sintomas

Fístula arteriovenosa dural intracraniana da junção craniocervical com drenagem venosa perimedular espinhal: um raro relato de caso

Fístulas arteriovenosas durais (FAVDs) são lesões adquiridas, que consistem em uma ou mais conexões fistulosas no interior dos folhetos da dura-máter, com envolvimento das paredes de um seio venoso dural ou então das veias leptomeníngeas adjacentes. Sua incidência é de difícil determinação, no entanto, segundo estudos, ela é estimada em 10% a 15% de todas as malformações cerebrovasculares diagnosticadas por angiografia. Os fatores predisponentes ao desenvolvimento das FAVDs são o traumatismo cranioencefálico, tromboflebite cerebral, neurocirurgia prévia e infecções. O objetivo deste estudo é apresentar um caso de Fístula Arteriovenosa Dural Intracraniana em um paciente de 58 anos, ressaltando os aspectos imagenológicos, etiológicos, fisiopatológicos e, sobretudo, os tipos de classificação da doença e a terapia utilizada. W.S.D., sexo masculino, 58 anos, natural e procedente de São Paulo – SP, deu entrada no pronto-socorro de um hospital de referência da capital paulista queixando-se de parestesia de membros superiores (MMSS) há 3 meses. Foi realizado exame físico e anamnese de forma minuciosa, na qual o paciente negou cefaleia e outros sintomas associados. Foi submetido à investigação com uma ressonância magnética (RNM) da região cerebral e medular em ponderações T1 e T2, as quais demonstraram efeito tumefativo que comprometia a transição bulbo-medular e a medula cervical de C2, as quais encontravam-se edemaciadas. Além disso, estavam proeminentes os vasos leptomeníngeos nos hemisférios cerebelares, estes patognomônicos da FAVD. Ademais, foi observado hipersinal em T2, com padrão estriado/tigroide, típico de degeneração mielínica progressiva. O paciente apresentava agressivo refluxo venoso cortical com drenagem perimedular espinhal na veia cortical e, dessa forma, enquadrou-se na Classificação de Cognard tipo V, sendo considerado um paciente portador de FAVD maligna. Foi então realizado tratamento endovascular com embolização transarterial, o qual proporcionou fechamento completo da fístula e, dessa forma, o paciente obteve um prognóstico favorável. As fístulas arteriovenosas durais, por serem uma condição rara e com variadas manifestações clínicas, podem passar despercebidas pelo profissional médico. Dessa forma, é de fundamental importância o conhecimento da doença, com o intuito de proporcionar ao paciente um diagnóstico precoce e uma terapia eficaz

Patologias atuais: a compulsão e a sociedade dos excessos: Current pathologies: compulsion and the society of excesses

O artigo em tela tem por objetivo analisar os aspectos biopsicossociais da conduta compulsiva de consumo. Propõe-se a apresentar os elementos psicológicos contidos nesse comportamento, além de verificar quais são os resultados decorrentes dessa compulsão. O consumo compulsivo, também chamado de oniomania, é um transtorno causado pela ansiedade despertada pela necessidade de comprar e saciada, somente, quando é materializada a aquisição daquilo que se deseja comprar. O estudo em questão pode ser classificado como sendo de cunho bibliográfico, a partir da análise de documentos publicados em forma de artigos científicos e livros em formato digital

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Les droits disciplinaires des fonctions publiques : « unification », « harmonisation » ou « distanciation ». A propos de la loi du 26 avril 2016 relative à la déontologie et aux droits et obligations des fonctionnaires

The production of tt‾ , W+bb‾ and W+cc‾ is studied in the forward region of proton–proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98±0.02 fb−1 . The W bosons are reconstructed in the decays W→ℓν , where ℓ denotes muon or electron, while the b and c quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions.The production of $t\overline{t}$, $W+b\overline{b}$ and $W+c\overline{c}$ is studied in the forward region of proton-proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98 $\pm$ 0.02 \mbox{fb}^{-1}. The $W$ bosons are reconstructed in the decays $W\rightarrow\ell\nu$, where $\ell$ denotes muon or electron, while the $b$ and $c$ quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good

Severe early onset preeclampsia: short and long term clinical, psychosocial and biochemical aspects

Preeclampsia is a pregnancy specific disorder commonly defined as de novo hypertension and proteinuria after 20 weeks gestational age. It occurs in approximately 3-5% of pregnancies and it is still a major cause of both foetal and maternal morbidity and mortality worldwide1. As extensive research has not yet elucidated the aetiology of preeclampsia, there are no rational preventive or therapeutic interventions available. The only rational treatment is delivery, which benefits the mother but is not in the interest of the foetus, if remote from term. Early onset preeclampsia (<32 weeks’ gestational age) occurs in less than 1% of pregnancies. It is, however often associated with maternal morbidity as the risk of progression to severe maternal disease is inversely related with gestational age at onset2. Resulting prematurity is therefore the main cause of neonatal mortality and morbidity in patients with severe preeclampsia3. Although the discussion is ongoing, perinatal survival is suggested to be increased in patients with preterm preeclampsia by expectant, non-interventional management. This temporising treatment option to lengthen pregnancy includes the use of antihypertensive medication to control hypertension, magnesium sulphate to prevent eclampsia and corticosteroids to enhance foetal lung maturity4. With optimal maternal haemodynamic status and reassuring foetal condition this results on average in an extension of 2 weeks. Prolongation of these pregnancies is a great challenge for clinicians to balance between potential maternal risks on one the eve hand and possible foetal benefits on the other. Clinical controversies regarding prolongation of preterm preeclamptic pregnancies still exist – also taking into account that preeclampsia is the leading cause of maternal mortality in the Netherlands5 - a debate which is even more pronounced in very preterm pregnancies with questionable foetal viability6-9. Do maternal risks of prolongation of these very early pregnancies outweigh the chances of neonatal survival? Counselling of women with very early onset preeclampsia not only comprises of knowledge of the outcome of those particular pregnancies, but also knowledge of outcomes of future pregnancies of these women is of major clinical importance. This thesis opens with a review of the literature on identifiable risk factors of preeclampsia

The global burden of adolescent and young adult cancer in 2019 : a systematic analysis for the Global Burden of Disease Study 2019

Background In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15-39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15-39 years to define adolescents and young adults. Findings There were 1.19 million (95% UI 1.11-1.28) incident cancer cases and 396 000 (370 000-425 000) deaths due to cancer among people aged 15-39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59.6 [54.5-65.7] per 100 000 person-years) and high-middle SDI countries (53.2 [48.8-57.9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14.2 [12.9-15.6] per 100 000 person-years) and middle SDI (13.6 [12.6-14.8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23.5 million (21.9-25.2) DALYs to the global burden of disease, of which 2.7% (1.9-3.6) came from YLDs and 97.3% (96.4-98.1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe