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

Síndrome da imunodeficiência adquirida: descrição anátomo-patológica de dois casos de necropsia

Two autopsy cases of acquired immunodeficiency disease syndrome are reported. One case showed widespread miliar cryptococcosis, with scarce inflammatory response. The other developed respiratory failure due to pulmonary infection by P. carinii. In both cases we could observe generalized cytomegalic infection, with striking adrenal involvement. Special emphasis is given to the pathologic changes and the possible etiopathogenic role of cytomegaloviroses in the acquired immunodeficiency cases.Os Autores apresentam dois casos de Síndrome de Imunodeficiência Adquirida com ênfase aos achados de necropsia. A criptococose generalizada de padrão miliar, infreqüente, e a pneumocistose foram infecções oportunísticas de curso fatal pela destruição parenquimatosa de órgãos vitais que acarretaram. É destacado o papel etiopatogênico do citomegalovírus, pela concomitância de infecção em ambos os casos e associação aos órgãos mais afetados. Extensa necrose de supra-renal foi constatada, possivelmente secundária à destruição celular viral pelo CMV

Cephalometric evaluation of facial pattern and hyoid bone position in children with obstructive sleep apnea syndrome

Objectives: To assess the development of face and hyoid bone in children with obstructive sleep apnea syndrome (OSAS) through lateral cephalometries. Materials and methods: Children aged 7-10 years with mixed dentition and with no previous otorhinolaryngologic, orthodontic or speech therapy treatments were studied. Twenty nasal breathers were compared to 20 mouth breathing children diagnosed as OSAS patients. All children underwent otorhinolaryngologic evaluation and cephalometries; children with OSAS also underwent nocturnal polysomnography in a sleep laboratory. Results: Children with OSAS presented increase in total and lower anterior heights of the face when compared to nasal breathers. In addition, children with OSAS presented a significantly more anterior and inferior position of the hyoid bone than nasal breathers. No significant differences in upper, anterior or posterior heights of the face were observed between groups. Conclusion: The results suggest that there are evident and early changes in facial growth and development among children with OSAS, characterized by increased total and inferior anterior heights of the face, as well as more anterior and inferior position of the hyoid bone. (C) 2010 Elsevier Ireland Ltd. All rights reserved

Influence of adenotonsillectomy on hard palate dimensions

Objective: To evaluate hard palate width and height in mouth-breathing children pre- and post-adenotonsillectomy. Methods: We evaluated 44 children in the 3-6 year age bracket, using dental study casts in order to determine palatal height, intercanine width, and intermolar width. The children were divided into two groups: nasal breathing (n = 15) and mouth breathing (n = 29). The children in the latter group underwent adenotonsillectomy. The study casts were obtained prior to adenotonsillectomy, designated time point 1(11), at 13 months after adenotonsillectomy (T2), and at 28 months after adenotonsillectomy (13). Similar periods of observation were obtained for nasal breathing children. Results: At T1, there was a significantly lower intercanine width in mouth breathing children; intermolar width and palate height were similar between groups. After surgery, there was a significant increase in all the analyzed parameters in both groups, probably due to facial growth. Instead, the increase in intercanine width was substantially more prominent in mouth breathing children than in nasal breathing children, and the former difference failed in significance after the procedure. Conclusions: There were no significant differences between the nasal-breathing and mouth-breathing children in terms of intermolar width and palatal height prior to or after tonsillectomy. Although intercanine width was initially narrower in the mouth-breathing children, it showed normalization after the surgical procedure. These results confirm that the restoration of nasal breathing is central to proper occlusal development. (C) 2012 Elsevier Ireland Ltd. All rights reserved

Aleitamento e hábitos orais deletérios em respiradores orais e nasais Breast-feeding and deleterious oral habits in mouth and nose breathers

OBJETIVO: A amamentação promove vários benefícios na criança, entre eles o favorecimento da respiração nasal. Neste estudo verificou-se a relação do padrão respiratório com o histórico de aleitamento e hábitos orais deletérios. FORMA DE ESTUDO: clínico com coorte transversal. MATERIAL E MÉTODO: A população foi constituída por 62 crianças, de 3 anos e 3 meses a 6 anos e 11 meses, as quais foram submetidas à avaliação otorrinolaringológica, para definição dos grupos respiradores nasais e orais e entrevista fonoaudiológica. A avaliação otorrinolaringológica constituiu-se dos seguintes exames: rinoscopia anterior, oroscopia e exame radiológico. Os pais das crianças foram questionados em relação à forma (natural e/ou artificial), e ao período de aleitamento, além da presença de hábitos orais deletérios (sucção e mordida). O teste Exato de Fisher foi utilizado para comparar os grupos em relação à presença ou ausência de hábitos e diferentes períodos de aleitamento. RESULTADOS: O período de aleitamento materno foi maior nos respiradores nasais concentrando-se no período de 3 a 6 meses de idade. Quanto ao uso de mamadeira, os resultados mostraram que a maioria das crianças de ambos os grupos utilizou-se deste tipo de aleitamento nos primeiros anos de vida, não apresentando diferença estatística entre os grupos (p=0.58). A presença de hábitos orais deletérios ocorreu de maneira marcante nos respiradores orais, evidenciando diferença estatisticamente significativa, entre os grupos, para os hábitos de sucção (p=0.004) e hábitos de mordida (p=0.0002). CONCLUSÃO: As crianças respiradoras orais apresentaram um menor período de aleitamento materno e um histórico de hábitos orais presentes comparadas às crianças respiradoras nasais.<br>AIM: Breast-feeding promotes several benefits in childhood, among them favoring the nasal breathing. In the present study, the relationship between breathing pattern and the history of breast-feeding and of deleterious oral habits was determined. STUDY DESIGN: clinical with transversal cohort. MATERIAL AND METHOD: The study population consisted of 62 children ranging in age from 3 years and 3 months to 6 years and 11 months who were submitted to otorhinolaryngologic evaluation to determine nasal and mouth breathers and to a speech language pathologic interview. The otorhinolaryngologic evaluation involved the following exams: anterior rhinoscopy, oroscopy and radiologic examination. The parents of the children were questioned about the form of feeding (natural and/or artificial), the duration of breast-feeding and the presence of deleterious oral habits (suction and biting). The Fisher exact test was used to compare groups regarding the presence and absence of habits and the different periods of breast-feeding. RESULTS: The breast-feeding period was longer among nasal breathers and was concentrated in the period between 3 and 6 months of age. Regarding the use of bottle, the results showed that most of the children in both groups used this type of feeding during the first years of life, with no significant difference between groups (p=0.58). There was a marked presence of deleterious oral habits among mouth breathers, with a statistically significant difference between groups regarding suction (p=0.004) and biting habits (p=0.0002). CONCLUSION: Mouth breathing children were breast-fed for a shorter period of time and had a history of deleterious oral habits compared to nose breathers