Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

Responsabilidade civil do médico e a inversão do pensamento jurídico sobre o tipo da atividade Liability of the physician and the turnaround of legal thinking about the kind of activity

Sempre que uma ação causar dano a outra pessoa e houver nexo causal, isto é, quando o resultado observado pela prática desta ação estiver, diretamente ou não, relacionado, caberá a obrigação de ressarcir à vítima, um valor referente ao seu dano. Esta normatização, Responsabilidade Civil, tem como fundamento o princípio da culpa, quando subjetiva (que tem necessidade de um ato ou omissão de violar o direito de uma segunda pessoa, o dano produzido por este ato, a responsabilidade de causalidade entre o ato e o dano e, finalmente, a culpa) e o princípio do risco quando objetivo (que não necessita de culpa, já que se baseia na teoria do risco, presumindo-a, independentemente de ter ou não agido com esta intenção). Enquanto Responsabilidade Civil Contratual, duas são as obrigações de um profissional: a de resultado, ou seja, a de alcançar determinado objetivo ou fim, e a de meio, ou seja, a obrigação de empregar todos os meios para consecução de seu objetivo. No Código de Proteção e Defesa do Consumidor (Lei 8.078, de 11 de setembro de 1990), a responsabilidade objetiva deve ser empregada a todos os prestadores de serviço à exceção da classe dos profissionais liberais, médicos e advogados, por realizarem suas atividades principalmente como sendo de meios e, portanto, considerada subjetiva. Em algumas situações, o Direito entende que a Responsabilidade deve ser objetiva, ou seja, quando ficar consubstanciado uma promessa de resultado. As peças publicitárias têm tido o poder de evocar estas equivocadas situações. O objetivo principal deste trabalho é mostrar, aos profissionais do Direito em geral e aos médicos em particular, quais são os fenômenos que criaram o desvio da norma. A Responsabilidade Civil Subjetiva se encontra amparada no Código Civil, em seu Art. 186 e no caput do Art. 927, enquanto a Objetiva é observada no Art. 927, § único. Desta forma, ao relacionar os textos da literatura jurídica e os dados do Conselho Regional de Medicina do Estado de São Paulo, quanto a peças publicitárias e sindicâncias instauradas sobre este sujeito, os autores pretendem demonstrar a relação causal desta nova forma de pensar.<br>Whenever an action causes damage to another person and there is causal nexus, that is, when the result seen by the practice of this action is, directly or not, related, the obligation will fit to repay the victim, a referring value to its damage. This normative, Civil Liability, has as bedding the beginning of the guilt, when subjective (which needs an act or omission that finally violates the right of a second person, the damage produced for this act, the responsibility of causality between the act and the damage and, the guilt) and the risk's beginning when objective (which does not need guilt, since is based on the theory of the risk, presuming it, independently to have or not acted with this intention). While Contractual Civil liability, two are the obligations of a professional: of result, that is, to reach definitive objective or end, and of way, that is, the obligation to use all the half ones for its objective achievement. In the Code of Protection and Defense of the Consumer (Law 8,078, of September 11, 1990), the objective responsibility must be used to all the service renders, except the class of liberal professionals, physicians, and lawyers, for carrying through its activities mainly as being of ways and, therefore, be considered subjective. In some situations, Law understands that the Responsibility should be objective, that is, when a result promise is consubstantiates. The advertisements have had the power to evoke these mistaken situations. The main objective of this paper is to show, to Law professionals and, in particularly, to the doctors, which are the phenomena that had created this shunting line of the norm. The Subjective Civil Liability is supported in the Civil Code, its Art.186 and the caption of the Art.927, while the Objective is observed in the Art. 927, only §. Thus, when relating legal literature texts and data from the Regional Medical Counsel of the State of São Paulo how much the advertisements and investigations restored on this citizen, the authors intend to demonstrate the causal relation of this new way of thinking

Erro médico em cirurgia do aparelho digestivo: contribuição para o estudo das provas técnicas, periciais e documentais e suas implicações jurídicas Medical malpractice in digestive system surgeries: a contribution to the study of technical, expertise and documentary evidence and its legal implications

RACIONAL: A preocupação dos indivíduos em relação aos erros médicos tem aumentado ultimamente entre os brasileiros e muitas vezes processos podem ser evitados com medidas racionais preventivas no relacionamento médico-paciente. OBJETIVO: Analisar processos judiciais, que tramitam pelos fóruns regionais cíveis do Estado de São Paulo, capital e interior e instituições periciais da capital para definir as principais causas e documentos juntados ao mesmo e conseqüências de cada condição. MÉTODOS: Trinta processos foram analisados onde se fez a extração individualizada de dados. Iniciou-se pela importância prática do tema para efeito de evolução médico-social. Buscou-se estudar a visão da relação médico-paciente, mesmo durante a demanda, a informação ao paciente e seus familiares dos procedimentos e limitadores do ato médico; o documental técnico jurídico juntado ao processo; o preparo técnico-jurídico do médico e, se, a propositura de ação dependia da formação e especialização do profissional. Foram analisados processos judiciais de primeira instância no período de 1996 a 2002 correlacionados às operações do aparelho digestivo. Usou-se como parâmetro de análise exclusivamente os documentos juntados aos autos onde buscou-se a existência clara da quebra da relação médico-paciente, a existência de consentimento informado, a verificação do documental juntado à defesa pelas partes ou solicitação judicial e a qualificação do profissional envolvido nas ações. RESULTADOS: Em 93,34% dos casos houve quebra da relação médico-paciente. Era visível das partes a animosidade no petitório. Em 10% dos casos existia consentimento informado, porém, apenas um foi usado e considerado pelo magistrado por descrever e orientar especificadamente sobre o risco que a posteriori originou a demanda. Dois eram genéricos, sendo que não foram considerados, ao ver do julgador, por hiposuficiência do paciente. Em 85% das vezes não havia história clínica completa. Em 79% não foi verificada a existência de exame físico. Em 80% dos casos a letra era ilegível. Em 59% não foi verificada a existência da evolução clínica. Em 61% não foram verificadas a identificação ou carimbo do médico. Em 89% não foi interrogado sobre a existência de alergias prévias. Somente em 20% dos casos observou-se descrição cirúrgica legível. Em 47% dos casos as descrições cirúrgicas eram de forma sumária sem as intercorrências alegadas pela defesa. Em 70% não houve visita pré-anestésica. Em 60% a prescrição médica de evolução ocorreu com mais que 24 horas no pós-operatório. Em 19% observou-se administração de medicação pela enfermagem posteriormente à alta médica. Em 64% dos casos não se observou a descrição das condições de alta. Em 7% o médico que figura como pólo passivo não possuía residência médica; em 13% estavam cursando residência ou estágio; em 67% possuíam título de especialização e em 13% dos casos mestrado ou doutorado. CONCLUSÃO: A melhor forma para profilaxia da ação cível indenizatória por erro médico é a boa relação médico-paciente; a manutenção de prontuário médico preenchido, legível, com carimbo e assinatura; o consentimento informado. A condição técnico-curricular do profissional não é fator atenuante para propositura da ação.<br>BACKGROUND: The fear of being prosecuted by their patients in relation to medical malpractice is growing among brazilian medical doctors. This condition may be avoided with preventive orientations. AIM: To analyze legal proceedings in course in the city and state of São Paulo as well as to define what could be the main cause regarding this concern and its consequences. METHODS: Thirty legal proceedings, which were in progress in the regional civil courts in the Capital and countryside of the State of São Paulo - Brazil have been analyzed. Trial court cases were selected from 1996 to 2002 related solely to digestive system surgery. The practical importance of the subject for the medical-social evolution has been addressed in the first place. The points looked for in this research were: physician/patient relationship (even during the claim); the information about medical procedures and limitations to the patient and family; the technical/legal documentation attached to the case; the professional's education and specialization. The analysis was based exclusively on the documents attached to the case record, trying to find the breach of the physician/patient relationship and the existence of informed consent. An examination of the documentation attached to the defense by the parties or court request, was also done. RESULTS: In 93,34% of the cases rupture in the physician/patient relationship occurred. Informed consent was found in only 10%. In 85% no or incomplete medical records were found. In 79%, absence of physical examination, and the same in 59% in clinical evolution, was noted. In 80% the writing was illegible. No medical identification was found in 61%. Information about previous allergies were not asked in 89% of the patients. Surgical descriptions were illegible in 80% and too brief in 47%, and all of them had no citation of the defense arguments to the malpractice accusation. Regarding medical post-graduation status, 7% had medical residency, 13% were in course of residency program, 67% had specialization certificates and 13% had a master or phD degree. CONCLUSION: Among the preventive ways to avoid a civil action for damages due to medical malpractice, the main points are: good relationship between doctors and patients; the formulation of complete patient records, being legible, stamped, and signed and an informed consent. The professional's technical experience and background do not constitute a mitigating circumstance for fullfiling the action