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2.
N Engl J Med ; 386(16): 1532-1546, 2022 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-35249272

RESUMO

BACKGROUND: A rapid increase in coronavirus disease 2019 (Covid-19) cases due to the omicron (B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 in highly vaccinated populations has aroused concerns about the effectiveness of current vaccines. METHODS: We used a test-negative case-control design to estimate vaccine effectiveness against symptomatic disease caused by the omicron and delta (B.1.617.2) variants in England. Vaccine effectiveness was calculated after primary immunization with two doses of BNT162b2 (Pfizer-BioNTech), ChAdOx1 nCoV-19 (AstraZeneca), or mRNA-1273 (Moderna) vaccine and after a booster dose of BNT162b2, ChAdOx1 nCoV-19, or mRNA-1273. RESULTS: Between November 27, 2021, and January 12, 2022, a total of 886,774 eligible persons infected with the omicron variant, 204,154 eligible persons infected with the delta variant, and 1,572,621 eligible test-negative controls were identified. At all time points investigated and for all combinations of primary course and booster vaccines, vaccine effectiveness against symptomatic disease was higher for the delta variant than for the omicron variant. No effect against the omicron variant was noted from 20 weeks after two ChAdOx1 nCoV-19 doses, whereas vaccine effectiveness after two BNT162b2 doses was 65.5% (95% confidence interval [CI], 63.9 to 67.0) at 2 to 4 weeks, dropping to 8.8% (95% CI, 7.0 to 10.5) at 25 or more weeks. Among ChAdOx1 nCoV-19 primary course recipients, vaccine effectiveness increased to 62.4% (95% CI, 61.8 to 63.0) at 2 to 4 weeks after a BNT162b2 booster before decreasing to 39.6% (95% CI, 38.0 to 41.1) at 10 or more weeks. Among BNT162b2 primary course recipients, vaccine effectiveness increased to 67.2% (95% CI, 66.5 to 67.8) at 2 to 4 weeks after a BNT162b2 booster before declining to 45.7% (95% CI, 44.7 to 46.7) at 10 or more weeks. Vaccine effectiveness after a ChAdOx1 nCoV-19 primary course increased to 70.1% (95% CI, 69.5 to 70.7) at 2 to 4 weeks after an mRNA-1273 booster and decreased to 60.9% (95% CI, 59.7 to 62.1) at 5 to 9 weeks. After a BNT162b2 primary course, the mRNA-1273 booster increased vaccine effectiveness to 73.9% (95% CI, 73.1 to 74.6) at 2 to 4 weeks; vaccine effectiveness fell to 64.4% (95% CI, 62.6 to 66.1) at 5 to 9 weeks. CONCLUSIONS: Primary immunization with two doses of ChAdOx1 nCoV-19 or BNT162b2 vaccine provided limited protection against symptomatic disease caused by the omicron variant. A BNT162b2 or mRNA-1273 booster after either the ChAdOx1 nCoV-19 or BNT162b2 primary course substantially increased protection, but that protection waned over time. (Funded by the U.K. Health Security Agency.).


Assuntos
Vacinas contra COVID-19 , COVID-19 , Eficácia de Vacinas , Vacina de mRNA-1273 contra 2019-nCoV/uso terapêutico , Vacina BNT162/uso terapêutico , COVID-19/prevenção & controle , Vacinas contra COVID-19/uso terapêutico , Estudos de Casos e Controles , ChAdOx1 nCoV-19/uso terapêutico , Humanos , Imunização Secundária/efeitos adversos , SARS-CoV-2/genética
3.
Nat Med ; 28(4): 831-837, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35045566

RESUMO

Booster vaccination with messenger RNA (mRNA) vaccines has been offered to adults in England starting on 14 September 2021. We used a test-negative case-control design to estimate the relative effectiveness of a booster dose of BNT162b2 (Pfizer-BioNTech) compared to only a two-dose primary course (at least 175 days after the second dose) or unvaccinated individuals from 13 September 2021 to 5 December 2021, when Delta variant was dominant in circulation. Outcomes were symptomatic coronavirus disease 2019 (COVID-19) and hospitalization. The relative effectiveness against symptomatic disease 14-34 days after a BNT162b2 or mRNA-1273 (Moderna) booster after a ChAdOx1-S (AstraZeneca) and BNT162b2 as a primary course ranged from around 85% to 95%. Absolute vaccine effectiveness ranged from 94% to 97% and was similar in all age groups. Limited waning was seen 10 or more weeks after the booster. Against hospitalization or death, absolute effectiveness of a BNT162b2 booster ranged from around 97% to 99% in all age groups irrespective of the primary course, with no evidence of waning up to 10 weeks. This study provides real-world evidence of substantially increased protection from the booster vaccine dose against mild and severe disease irrespective of the primary course.


Assuntos
COVID-19 , Adulto , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19/uso terapêutico , Inglaterra/epidemiologia , Hospitalização , Humanos , Lactente , SARS-CoV-2 , Vacinas de mRNA
4.
BMC Health Serv Res ; 11: 155, 2011 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-21714903

RESUMO

BACKGROUND: Due to increasing demand and financial constraints, NHS continuing healthcare systems seek to find better ways of forecasting demand and budgeting for care. This paper investigates two areas of concern, namely, how long existing patients stay in service and the number of patients that are likely to be still in care after a period of time. METHODS: An anonymised dataset containing information for all funded admissions to placement and home care in the NHS continuing healthcare system was provided by 26 (out of 31) London primary care trusts. The data related to 11289 patients staying in placement and home care between 1 April 2005 and 31 May 2008 were first analysed. Using a methodology based on length of stay (LoS) modelling, we captured the distribution of LoS of patients to estimate the probability of a patient staying in care over a period of time. Using the estimated probabilities we forecasted the number of patients that are likely to be still in care after a period of time (e.g. monthly). RESULTS: We noticed that within the NHS continuing healthcare system there are three main categories of patients. Some patients are discharged after a short stay (few days), some others staying for few months and the third category of patients staying for a long period of time (years). Some variations in proportions of discharge and transition between types of care as well as between care groups (e.g. palliative, functional mental health) were observed. A close agreement of the observed and the expected numbers of patients suggests a good prediction model. CONCLUSIONS: The model was tested for care groups within the NHS continuing healthcare system in London to support Primary Care Trusts in budget planning and improve their responsiveness to meet the increasing demand under limited availability of resources. Its applicability can be extended to other types of care, such as hospital care and re-ablement. Further work will be geared towards updating the dataset and refining the results.


Assuntos
Hospitais Públicos , Tempo de Internação/tendências , Medicina Estatal , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Bases de Dados Factuais , Feminino , Necessidades e Demandas de Serviços de Saúde , Humanos , Lactente , Tempo de Internação/economia , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Cuidados Paliativos , Atenção Primária à Saúde , Sobrevida , Adulto Jovem
5.
Gynecol Oncol ; 96(2): 430-8, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15661232

RESUMO

OBJECTIVES: The antioxidant status of cancer cells is an important factor in tumor invasion and metastases. This study investigated whether metastatic cancer cells derive beneficial antioxidant protection from ascitic fluid and are rendered resistant to oxidative stress in the form of a chemically generated free radical insult. METHODS: Human gastric carcinoma (KATO-III) and ovarian adenocarcinoma (SKOV-3) cell lines were cultured and incubated for 24 h with (1) M199 medium; (2) M199 + 20% fetal calf serum (FCS); (3) malignant ascites. All cells were exposed to a hydroxyl radical-generating system for 1 h. Cellular lipid peroxidation was assessed by measuring malondialdehyde (MDA) in cell suspensions. Glutathione (GSH) levels in cell pellet were measured in SKOV-3 cells after 0, 24, 48, and 72 h of incubation with buthionine sulphoximine (BSO). CD44 gene expression of cancer cells was analyzed by Northern blotting. RESULTS: The results showed that the cancer cells were rendered resistant to oxidative stress and with upregulated CD44 gene expression by components of malignant ascites. CONCLUSIONS: These findings suggest that malignant ascites increases the antioxidant ability of cancer cells and the potential of adhesion and invasion. Thus, determination of the nature of these putative tumor-protective components of ascites may provide targets for therapeutic intervention.


Assuntos
Adenocarcinoma/metabolismo , Antioxidantes/metabolismo , Ascite/metabolismo , Neoplasias Ovarianas/metabolismo , Neoplasias Gástricas/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/patologia , Ascite/patologia , Northern Blotting , Butionina Sulfoximina/farmacologia , Adesão Celular/fisiologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Expressão Gênica , Glutationa/deficiência , Glutationa/metabolismo , Humanos , Receptores de Hialuronatos/biossíntese , Receptores de Hialuronatos/genética , Peroxidação de Lipídeos , Malondialdeído/metabolismo , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Estresse Oxidativo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
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