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Cochrane Database Syst Rev ; 4: CD005351, 2019 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-30950507


BACKGROUND: Non-invasive positive pressure ventilation (NPPV) has been used to treat respiratory distress due to acute cardiogenic pulmonary oedema (ACPE). We performed a systematic review and meta-analysis update on NPPV for adults presenting with ACPE. OBJECTIVES: To evaluate the safety and effectiveness of NPPV compared to standard medical care (SMC) for adults with ACPE. The primary outcome was hospital mortality. Important secondary outcomes were endotracheal intubation, treatment intolerance, hospital and intensive care unit length of stay, rates of acute myocardial infarction, and adverse event rates. SEARCH METHODS: We searched CENTRAL (CRS Web, 20 September 2018), MEDLINE (Ovid, 1946 to 19 September 2018), Embase (Ovid, 1974 to 19 September 2018), CINAHL Plus (EBSCO, 1937 to 19 September 2018), LILACS, WHO ICTRP, and We also reviewed reference lists of included studies. We applied no language restrictions. SELECTION CRITERIA: We included blinded or unblinded randomised controlled trials in adults with ACPE. Participants had to be randomised to NPPV (continuous positive airway pressure (CPAP) or bilevel NPPV) plus standard medical care (SMC) compared with SMC alone. DATA COLLECTION AND ANALYSIS: Two review authors independently screened and selected articles for inclusion. We extracted data with a standardised data collection form. We evaluated the risks of bias of each study using the Cochrane 'Risk of bias' tool. We assessed evidence quality for each outcome using the GRADE recommendations. MAIN RESULTS: We included 24 studies (2664 participants) of adult participants (older than 18 years of age) with respiratory distress due to ACPE, not requiring immediate mechanical ventilation. People with ACPE presented either to an Emergency Department or were inpatients. ACPE treatment was provided in an intensive care or Emergency Department setting. There was a median follow-up of 13 days for hospital mortality, one day for endotracheal intubation, and three days for acute myocardial infarction. Compared with SMC, NPPV may reduce hospital mortality (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.51 to 0.82; participants = 2484; studies = 21; I2 = 6%; low quality of evidence) with a number needed to treat for an additional beneficial outcome (NNTB) of 17 (NNTB 12 to 32). NPPV probably reduces endotracheal intubation rates (RR 0.49, 95% CI 0.38 to 0.62; participants = 2449; studies = 20; I2 = 0%; moderate quality of evidence) with a NNTB of 13 (NNTB 11 to 18). There is probably little or no difference in acute myocardial infarction (AMI) incidence with NPPV compared to SMC for ACPE (RR 1.03, 95% CI 0.91 to 1.16; participants = 1313; studies = 5; I2 = 0%; moderate quality of evidence). We are uncertain as to whether NPPV increases hospital length of stay (mean difference (MD) -0.31 days, 95% CI -1.23 to 0.61; participants = 1714; studies = 11; I2 = 55%; very low quality of evidence). Adverse events were generally similar between NPPV and SMC groups, but evidence was of low quality. AUTHORS' CONCLUSIONS: Our review provides support for continued clinical application of NPPV for ACPE, to improve outcomes such as hospital mortality and intubation rates. NPPV is a safe intervention with similar adverse event rates to SMC alone. Additional research is needed to determine if specific subgroups of people with ACPE have greater benefit of NPPV compared to SMC. Future research should explore the benefit of NPPV for ACPE patients with hypercapnia.

Pressão Positiva Contínua nas Vias Aéreas/métodos , Mortalidade Hospitalar , Edema Pulmonar/terapia , Adulto , Pressão Positiva Contínua nas Vias Aéreas/efeitos adversos , Humanos , Unidades de Terapia Intensiva , Intubação Intratraqueal/estatística & dados numéricos , Tempo de Internação , Ventilação não Invasiva , Ensaios Clínicos Controlados Aleatórios como Assunto
Biotechnol J ; 12(8)2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28504349


mRNA translation is a key process determining growth, proliferation and duration of a Chinese hamster ovary (CHO) cell culture and influences recombinant protein synthesis rate. During bioprocessing, CHO cells can experience stresses leading to reprogramming of translation and decreased global protein synthesis. Here we apply polysome profiling to determine reprogramming and translational capabilities in host and recombinant monoclonal antibody-producing (mAb) CHO cell lines during batch culture. Recombinant cell lines with the fastest cell specific growth rates were those with the highest global translational efficiency. However, total ribosomal capacity, determined from polysome profiles, did not relate to the fastest growing or highest producing mAb cell line, suggesting it is the ability to utilise available machinery that determines protein synthetic capacity. Cell lines with higher cell specific productivities tended to have elevated recombinant heavy chain transcript copy numbers, localised to the translationally active heavy polysomes. The highest titre cell line was that which sustained recombinant protein synthesis and maintained high recombinant transcript copy numbers in polysomes. Investigation of specific endogenous transcripts revealed a number that maintained or reprogrammed into heavy polysomes, identifying targets for potential cell engineering or those with 5' untranslated regions that might be utilised to enhance recombinant transcript translation.

Anticorpos Monoclonais/genética , Polirribossomos/genética , Biossíntese de Proteínas , Proteínas Recombinantes/biossíntese , Animais , Anticorpos Monoclonais/biossíntese , Técnicas de Cultura Celular por Lotes , Células CHO , Engenharia Celular/métodos , Proliferação de Células/genética , Cricetulus , Polirribossomos/química , RNA Mensageiro/genética , Proteínas Recombinantes/genética , Ribossomos