Serious Adverse Events Reporting in Phase III Randomized Clinical Trials of Colorectal Cancer Treatments: A Systematic Analysis

Objective: The occurrence, development, and prognosis of serious adverse events (SAEs) associated with anticancer drugs in clinical trials have important guiding significance for real-world clinical applications. However, to date, there have been no studies investigating SAEs reporting in randomized clinical trials of colorectal cancer treatments. This article systematically reviewed the SAEs reporting of phase III randomized clinical trials of colorectal cancer treatments and analyzed the influencing factors.Methods: We reviewed all articles about phase III randomized clinical trials of colorectal cancer treatments published in the PubMed, Embase, Medline, and New England Journal of Medicine databases from January 1, 1993, to December 31, 2018, and searched the registration information of clinical trials via the internet sites such as “clinicaltrials.gov”. We analyzed the correlation between the reported proportion (RP) of SAEs in the literature and nine elements, including the clinical trial sponsor and the publication time. Chi-square tests and binary logistic regression were used to identify the factors associated with improved SAEs reports. This study was registered on PROSPERO.Results: Of 1560 articles identified, 160 were eligible, with an RP of SAEs of 25.5% (41/160). In forty-one publications reporting SAEs, only 14.6% (6/41) described the pattern of SAEs in detail. In clinical trials sponsored by pharmaceutical companies, the RP of SAEs was significantly higher than that in those sponsored by investigators (57.6 versus 20.7%, p < 0.001). From 1993 to 2018, the RP of SAEs gradually increased (none (0/6) before 2000, 17.1% (12/70) from 2000 to 2009, and 34.5% (29/84) after 2009). The average RP of SAEs published in the New England Journal of Medicine (N Engl J Med), the Lancet, the Journal of the American Medical Association (JAMA), the Lancet Oncology (Lancet Oncol), and the Journal of Clinical Oncology (J Clin Oncol) was significantly higher than that published in other journals (31.9 versus 16.7%, p = 0.030). In the clinical trials referenced by clinical guidelines, the RP of SAEs was higher than that in non-referenced clinical trials (32.0 versus 15.9%, p = 0.023). Binary logistic regression analysis showed that pharmaceutical company sponsorship, new drug research, and sample size greater than 1000 were positive influencing factors for SAEs reporting.Conclusion: Although the RP of SAEs increased over time, SAEs reporting in clinical trials needs to be further improved. The performance, outcomes and prognosis of SAEs should be reported in detail to guide clinical practice in the real world.

Diferentes aspectos da resposta imunológica na COVID-19

Durante a pandemia da COVID-19, infecção pelo vírus SARS-CoV-2, o qual provoca síndrome respiratória grave. Diferente de outras infecções virais, sua resposta a inflamação diverge do comum, assim se tornou um enigma para compreender o funcionamento celular durante a resposta imunológica. Sendo assim muitos estudos permitiram iniciar a elucidação a partir das células principais, TCD4, TCD8, Linfócitos B e Anticorpos. Esta revisão tem como objetivo buscar em artigos e pesquisas cientificas relacionadas ao tema, via bases de dados como: Google Scholar, Elsevier, PubMed, Medline, The New England Journal of Medicine e Scielo, textos relacionados às características gerais do COVID-19 e a imunologia relacionada à infecção pelo vírus SARS-CoV-2. Embora mais estudos sejam necessários, uma imagem começou a emergir que revela que Células TCD4 +, células TCD8 + e anticorpos neutralizantes, contribuem para o controle de SARS-CoV-2 em ambos os casos não hospitalizados e hospitalizados de COVID-19. As funções específicas e cinética destes adaptativos as respostas imunes são discutidas, bem como sua interação com a imunidade inata e implicações para COVID-19 vacinas e memória imunológica contra reinfecção, deve-se lembrar que mesmo com as conclusões supracitas, hoje existem variantes do vírus, as quais fazem repensar sobre a eficácia da imunidade de rebanho e imunidade geral, pois elas podem ser mais transmissíveis e mais resistentes a vacinas. Sendo assim ressaltamos a importância de manter os cuidados relacionados a higiene e proteção, seguindo o recomendado pelas agências de saúde mundiais.

Risk of heparinoid use in cosmetics and moisturizers in individuals vaccinated against severe acute respiratory syndrome coronavirus 2

Recently, heparin-induced thrombocytopenia (HIT) after vaccination with the vaccines manufactured by AstraZeneca and Pfizer–BioNTech has been published in the New England Journal of Medicine. These reports state that heparin was not used around the vaccination period in all cases. HIT after vaccination is more common in women; thus, heparinoid use can be suspected to induce HIT.

Accuracy of Conflict-of-Interest Disclosures of Physician-Authors Publishing in High-Impact U.S. Medical Journals: A Comparison of the Journal of the American Medical Association and the New England Journal of Medicine

Objective: To assess the accuracy of self-reported financial conflict-of-interest (COI) disclosures in the New England Journal of Medicine (NEJM) and Journal of the American Medical Association (JAMA) within the requisite disclosure period prior to article submission. Design: Cross-sectional investigation. Data Sources: Original clinical-trial research articles published in NEJM (n = 206) or JAMA (n = 188) from January 1 to December 31, 2017; self-reported COI disclosure forms submitted to NEJM or JAMA with the authors published articles; Open Payments website (from database inception; latest search: August 2019). Main outcome measures: Financial data reported to Open Payments from 2014 to 2016 (time period that included all subjects requisite disclosure windows) were compared to self-reported disclosure forms submitted to the journals. Payments were defined as those not associated with a research study or formal research funding. Payment types were categorized as disclosed, undisclosed, indeterminate, or unrelated. Results: Thirty-one articles from NEJM and 31 articles from JAMA met inclusion criteria. The physician-authors (n = 118) received a combined total of $7.48 million. Of the 106 authors (89.8%) who received payments, 86 (81.1%) received undisclosed payments. The top 23 most highly compensated received $6.32 million, of which $3.00 million (47.6%) was undisclosed. Disclosure rates were the equivalent between the top 23 and the entire sample. Conclusions: High payment amounts, as well as high proportions of undisclosed financial compensation, regardless of amount received, comprised potential COIs for two influential US medical journals. Further research is needed to explain why such high proportions of general payments were undisclosed and whether journals that rely on self-reported COI disclosure need to reconsider their policies.

FETO: Krankheitsschwere und Überleben

Die fetoskopische endotracheale Okklusion (FETO) zur Behandlung der kongenitalen Zwerchfellhernie wird kontrovers diskutiert. In Beobachtungsstudien stand eine reduzierte Mortalität schweren Komplikationen gegenüber. Im New England Journal of Medicine erschienen nun zwei Berichte prospektiv- zur randomisierten TOTAL-Studie, in der Feten mit unterschiedlich ausgeprägter linksseitiger Zwerchfellhernie eine FETO im Vergleich zu einer Kontrollgruppe erhielten.

Prevenção Quaternária e a Prescrição de Cloroquina e Hidroxicloroquina na COVID-19

Prevenção quaternária: ação feita para reconhecer pessoas ou populações em risco de supermedicalização e protegê-las, sugerindo procedimentos científica e eticamente aceitáveis. Em 2019, emergiu em Wuhan, uma doença classificada como Coronavirus-Induced-Disease, responsável pela pandemia por COVID-19. Vidas estão sendo ceifadas e a busca por tratamento é uma questão de saúde pública planetária. In vitro, a hidroxicloroquina e a cloroquina inibem esse agente, sendo sugerido que tais medicamentos fizessem parte do tratamento precoce. Realizou-se uma revisão em bancos de dados PubMed e LILACS e busca manual de periódicos no The New England Journal of Medicine (NEJM) e no Journal of the American Medical Association (JAMA), pelos termos: “hidroxicloroquina, cloroquina e COVID-19”, “hydroxychloroquine, chloroquine and COVID-19” e “cloroquina e COVID-19”. Critérios de exclusão: artigos duplicados, hidroxicloroquina e cloroquina fora do contexto da COVID-19, outros aspectos da COVID-19 e revistas patrocinadas pela indústria farmacêutica. Foram encontrados 115 artigos nos bancos de dados, após a aplicação dos critérios de exclusão e 6 foram selecionados para a revisão. Pesquisou-se outros estudos sobre prevenção quaternária, a fim de discutir o excesso de intervenção médica. Ainda não existe um tratamento ideal para controlar o vírus. Cabe aos profissionais de saúde, em especial, os Médicos de Família e Comunidade, o pensamento crítico aplicado a todos os resultados apresentados nos estudos, por mais atrativos que estes pareçam à primeira vista.

Bibliometric Analysis of Pfizer-BioNTech (BNT162B2): A COVID-19 Vaccine

The objective of the study was to perform a bibliometric analysis of the Pfizer-BioNTech vaccine. For this purpose Scopus database was used. As of 13th May 2021, one hundred and seventy-three (n=173) research documents are published about it. We used Vosviewer and Biblioshiny (Bibliometrix) in the present report. In all publications, 1160 authors have significantly contributed. The documents per author was 0.119, while authors per document was 8.41. Collaborative Index (CI) was found to be 9.47. By biblioshiny we also applied Lotka’s law to depict the author's frequency. 1097 authors were involved in only one (n=1) publication. Based on the Scopus record, the highest documents are published by Dormitzer, P.R. (n=6). In universities and countries categories, Tel Aviv University (n=7) and USA (48) are the most productive. By Vosviewer the collaboration pattern among authors, institutes, and countries is graphically presented. For example, 28 authors, 17 departments and 7 countries directly contributed to one publication. The research documents (133) are published in 102 sources or journals. The highest documents are published in Vaccines (n=8), while the highest citations were recorded for the New England Journal of Medicine (n=838). We also applied co-words analysis to understand the main focus of these publications.

Der Stellenwert der Thymektomie ohne Thymom in der Therapie der Myasthenia gravis

ZusammenfassungDer Stellenwert der Thymektomie in der Therapie der thymomfreien Myasthenia gravis blieb bis vor einiger Zeit umstritten. Die relativ geringe Inzidenz und Prävalenz der Erkrankung, die uneinheitliche Dokumentation in den verschiedenen Studien sowie die notwendige Langzeitbeobachtung zur Erfassung therapeutischer Effekte erschwerten das Generieren valider Daten. Die Veröffentlichung des MGTX-Trials 2016 im New England Journal of Medicine lieferte die ersten randomisiert-kontrollierten Daten, nach denen Patienten mit Acetylcholin-Rezeptor-Antikörper-positiver generalisierter Myasthenia gravis im Alter von 18 bis 65 Jahren von der chirurgischen Resektion des Thymus über eine mediane Sternotomie profitieren. Trotz fehlender Validierung des Vorteils der Thymektomie über minimal-invasive Techniken durch randomisiert-kontrollierte Studien scheinen diese das Outcome bestimmter Patientengruppen in ähnlicher Form positiv zu beeinflussen. So haben videoassistiert-thorakoskopische, roboterassistierte, subxiphoidale und transzervikale Zugangswege nicht nur ästhetische Vorteile, sondern zeigen in der Beeinflussung des Krankheitsverlaufs der Myasthenia gravis keine relevante Unterlegenheit gegenüber der medianen Sternotomie. Doch nicht nur der Nutzen und das ästhetische Ergebnis differieren, sondern auch die Erfolgsaussichten im Hinblick auf die Remission sind bei den Unterformen der Myasthenia gravis unterschiedlich. Die heterogene Gruppe der Myasthenien unterscheidet sich bezüglich des Auftretens von Autoantikörpern, der betroffenen Körperregionen und des Alters der Patienten bei Erstdiagnose. Schließlich ist die Thymektomie eine wirksame kausale Therapie der Myasthenia gravis.