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1.
Ann Oncol ; 33(12): 1250-1268, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36228963

RESUMO

BACKGROUND: The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. PATIENTS AND METHODS: One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. RESULTS: With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Δ 3.4%, 95% CI -0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Δ 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Δ 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. CONCLUSION: With 3.5 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDFS and DDFS with no new safety signals.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Ftalazinas/efeitos adversos , Células Germinativas/patologia , Proteína BRCA1/genética
2.
J Med Syst ; 38(10): 134, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25178272

RESUMO

Clinical terminologies are considered a key technology for capturing clinical data in a precise and standardized manner, which is critical to accurately exchange information among different applications, medical records and decision support systems. An important step to promote the real use of clinical terminologies, such as SNOMED-CT, is to facilitate the process of finding mappings between local terms of medical records and concepts of terminologies. In this paper, we propose a mapping tool to discover text-to-concept mappings in SNOMED-CT. Name-based techniques were combined with a query expansion system to generate alternative search terms, and with a strategy to analyze and take advantage of the semantic relationships of the SNOMED-CT concepts. The developed tool was evaluated and compared to the search services provided by two SNOMED-CT browsers. Our tool automatically mapped clinical terms from a Spanish glossary of procedures in pathology with 88.0% precision and 51.4% recall, providing a substantial improvement of recall (28% and 60%) over other publicly accessible mapping services. The improvements reached by the mapping tool are encouraging. Our results demonstrate the feasibility of accurately mapping clinical glossaries to SNOMED-CT concepts, by means a combination of structural, query expansion and named-based techniques. We have shown that SNOMED-CT is a great source of knowledge to infer synonyms for the medical domain. Results show that an automated query expansion system overcomes the challenge of vocabulary mismatch partially.


Assuntos
Automação , Codificação Clínica , Processamento de Linguagem Natural , Patologia/classificação , Systematized Nomenclature of Medicine , National Library of Medicine (U.S.) , Melhoria de Qualidade , Espanha , Estados Unidos
3.
Rev Esp Anestesiol Reanim (Engl Ed) ; 71(1): 58-63, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37666451

RESUMO

We describe a series of 11 cases in which we used the new flexible tip (FlexTip) bougie as a rescue device following first-attempt failure at intubation with the C-MAC D-Blade video laryngoscope in our UCI. We collected data from all intubations performed using the C-MAC D-Blade video laryngoscope over a 16-month period. Ninety six patients were included in the study: 79 (86.8%) were intubated at the first attempt; 11 (12.1%) required 2 attempts; and 1 patient required 3 attempts. The Frova Intubating Introducer was used in 1 of the 12 patients requiring more than 1 intubation attempt, and the FlexTip was used in the remaining 11. This study shows that the new FlexTip bougie is a good rescue device when the first attempt at video laryngoscope intubation fails.


Assuntos
Laringoscópios , Humanos , Unidades de Terapia Intensiva , Intubação Intratraqueal , Estudos Prospectivos
4.
Rev Esp Anestesiol Reanim (Engl Ed) ; 71(1): 17-27, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38104962

RESUMO

OBJECTIVE: The objective of our study was to compare the degree of difficulty and complications related to tracheal intubation in an Intensive Care Unit (ICU) before and after the introduction of an intubation protocol based on the Difficult Airway Society guidelines for the management of tracheal intubation in critically ill adults, published in 2018. METHODS: Prospective, observational study comparing all intubations performed in our ICU over 2 periods: pre-protocol (January 2015-January 2019) and post-protocol (February 2019-July 2022). The material used for intubation, the degree of difficulty, and intubation-related complications were recorded. RESULTS: During the study period, 661 patients were intubated - 437 in the pre-protocol period (96% by direct laryngoscopy) and 224 in the post-protocol period (53% with direct laryngoscopy, 46% with video laryngoscopy). We observed an improvement in laryngeal view in the post-protocol period compared to the pre-protocol period (Cormack-Lehane ≥ 2b in 7.6% vs. 29.8%, p < 0.001), and a decrease in the number of moderate-to-severely difficult intubations (6.7% vs. 17.4%, p < 0.001). The first-pass success rate was 92.8% in the post-protocol period compared to 90.2% pre-protocol (p = 0.508). We did not find significant differences in complications between the periods studied. CONCLUSIONS: Intubations performed in the post-protocol period were associated with improved laryngeal view and fewer cases of difficult intubation compared with the pre-protocol period.


Assuntos
Estado Terminal , Intubação Intratraqueal , Adulto , Humanos , Estado Terminal/terapia , Unidades de Terapia Intensiva , Intubação Intratraqueal/métodos , Laringoscopia/métodos , Estudos Prospectivos
5.
Br J Cancer ; 108(6): 1316-23, 2013 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-23449351

RESUMO

BACKGROUND: The prognostic/predictive value of potential vascular endothelial growth factor (VEGF) signalling biomarkers was evaluated retrospectively using samples from two randomized Phase III studies (HORIZON II and III) investigating cediranib in metastatic colorectal cancer (mCRC). METHODS: Baseline levels of VEGF, soluble VEGF receptor-2 (sVEGFR-2) and carcinoembryonic antigen (CEA) were measured in plasma/serum samples collected from patients participating in HORIZON II (n=860; FOLFOX/XELOX plus cediranib 20 mg (n=502) or placebo (n=358)) and HORIZON III (n=1422; mFOLFOX6 plus cediranib 20 mg (n=709) or bevacizumab (n=713)). Median biomarker baseline levels determined cutoff values for the patient subgroups. RESULTS: Baseline data were available for 88-97% of patients/study (>2000 patients). In both the studies, high baseline VEGF and CEA were associated with worse outcomes for progression-free survival (PFS) and overall survival (OS) independent of treatment (HORIZON II OS: VEGF, hazard ratio (HR)=1.35 (95% confidence interval (CI): 1.12-1.63); CEA, HR=1.63 (1.36-1.96); HORIZON III OS: VEGF, HR=1.32 (1.12-1.54); CEA, HR=1.50 (1.29-1.76)). sVEGFR-2 was not prognostic for PFS/OS. Baseline VEGF and CEA were not predictive for PFS/OS outcome to cediranib treatment; low sVEGFR-2 was associated with a trend towards improved cediranib effect in HORIZON II. CONCLUSION: Baseline VEGF and CEA levels were treatment-independent prognostic biomarkers for PFS and OS in both the studies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno Carcinoembrionário/sangue , Neoplasias Colorretais/mortalidade , Fator A de Crescimento do Endotélio Vascular/sangue , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/sangue , Anticorpos Monoclonais Humanizados/administração & dosagem , Bevacizumab , Biomarcadores Tumorais/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/tratamento farmacológico , Ensaio de Imunoadsorção Enzimática , Seguimentos , Humanos , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Quinazolinas/administração & dosagem , Estudos Retrospectivos , Taxa de Sobrevida
6.
J Biomed Inform ; 46(3): 388-400, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23402961

RESUMO

OBJECTIVE: To explore semantic search to improve management and user navigation in clinical archetype repositories. METHODS: In order to support semantic searches across archetypes, an automated method based on SNOMED CT modularization is implemented to transform clinical archetypes into SNOMED CT extracts. Concurrently, query terms are converted into SNOMED CT concepts using the search engine Lucene. Retrieval is then carried out by matching query concepts with the corresponding SNOMED CT segments. RESULTS: A test collection of the 16 clinical archetypes, including over 250 terms, and a subset of 55 clinical terms from two medical dictionaries, MediLexicon and MedlinePlus, were used to test our method. The keyword-based service supported by the OpenEHR repository offered us a benchmark to evaluate the enhancement of performance. In total, our approach reached 97.4% precision and 69.1% recall, providing a substantial improvement of recall (more than 70%) compared to the benchmark. CONCLUSIONS: Exploiting medical domain knowledge from ontologies such as SNOMED CT may overcome some limitations of the keyword-based systems and thus improve the search experience of repository users. An automated approach based on ontology segmentation is an efficient and feasible way for supporting modeling, management and user navigation in clinical archetype repositories.


Assuntos
Systematized Nomenclature of Medicine , Benchmarking , Armazenamento e Recuperação da Informação , Reprodutibilidade dos Testes
7.
Nutr Metab Cardiovasc Dis ; 22(2): 103-8, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20675108

RESUMO

BACKGROUND AND AIMS: Patients with stable coronary heart disease (CHD) and atherogenic dyslipidemia (AD) have a high-risk of recurrence and are those who derive most benefit from treatment with lipid-lowering agents. The aim of this study was to examine the prevalence of AD in patients with stable coronary heart disease and to investigate associated factors. METHODS: Cross-sectional study involving 7823 subjects admitted for a coronary event between 6 months and 10 years previously. AD was considered to be the concurrent presence of low HDL-cholesterol (<1.03 mmol/L [40 mg/dL] in males, <1.29 mmol/L [50 mg/dL] in females) and elevated triglycerides (≥1.7 mmol/L [150 mg/dL]). RESULTS: Mean age was 65.3 (10.1) years, 73.6% were males and 80.3% were receiving treatment with statins. Low HDL-cholesterol was observed in 26.3% of the participants, 39.7% had elevated triglyceride concentration and 13.0% had AD. The percentage of AD in patients with criteria for metabolic syndrome was 30.9%. Factors associated directly and independently with the presence of AD in the multivariate analysis were female sex, history of coronary syndrome without ST elevation or coronary revascularization, presence of atrial fibrillation, body mass index, LDL-cholesterol, systolic blood pressure and blood glucose levels, while age and glomerular filtration rate were significantly and inversely associated with AD. CONCLUSION: A significant proportion of patients with coronary disease could benefit from interventions aimed at increasing HDL-cholesterol and reducing triglycerides.


Assuntos
Aterosclerose/sangue , Aterosclerose/epidemiologia , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/epidemiologia , Dislipidemias/sangue , Dislipidemias/epidemiologia , Idoso , Aterosclerose/complicações , Índice de Massa Corporal , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Doença da Artéria Coronariana/complicações , Estudos Transversais , Dislipidemias/complicações , Feminino , Humanos , Hipolipemiantes/farmacologia , Masculino , Pessoa de Meia-Idade , Prevalência , Triglicerídeos/sangue
8.
Artigo em Inglês | MEDLINE | ID: mdl-35760688

RESUMO

BACKGROUND: Hospitalized COVID-19 patients are prone to develop persistent symptoms and to show reduced quality of life following hospital admission. METHODS: Prospective cohort study of COVID-19 patients admitted to a hospital from March 1 to April 30, 2020. The primary outcome was to compare health related quality of life and persistent symptoms six months after hospital admission, of COVID-19 patients who required ICU admission with those who did not. RESULTS: Among the 242 patients hospitalized during the defined period of time, 44 (18.2%) needed ICU admission. Forty (16.5%) patients died during hospital admission. Two hundred and two (83.5%) patients were discharged alive from the hospital. At six months, 183 (75.6%) patients completed the questionnaires (32 ICU patients and 151 non ICU patients). Ninety-six (52.4%) reported decreased quality of life and 143 (78.1%) described persistent symptoms. More ICU patients showed worsening of their quality of life (71.9% vs 43.7%, P=0.004). There were no differences in the proportion of patients with persistent symptoms between ICU and non ICU patients (87.5% vs 76.2%, P=0.159). ICU patients showed more frequently dyspnea on exertion (78.1% vs 47.7%, P=0.02), dyspnea on light exertion (37.5% vs 4.6%, P<0.001), and asthenia (56.3 vs 29.1, P=0.003). CONCLUSIONS: Survivors of COVID-19 needing hospitalization had persistent symptoms and a decline in the quality of life. ICU patients referred a large decrease of their quality of life compared with non ICU patients.


Assuntos
COVID-19 , COVID-19/complicações , Dispneia , Hospitalização , Humanos , Unidades de Terapia Intensiva , Estudos Prospectivos , Qualidade de Vida , SARS-CoV-2
9.
Rev Esp Anestesiol Reanim ; 69(6): 326-335, 2022.
Artigo em Espanhol | MEDLINE | ID: mdl-34176973

RESUMO

Background: Hospitalized COVID-19 patients are prone to develop persistent symptoms and to show reduced quality of life following hospital admission. Methods: Prospective cohort study of COVID-19 patients admitted to a hospital from March 1 to April 30, 2020. The primary outcome was to compare health related quality of life and persistent symptoms six months after hospital admission, of COVID-19 patients who required ICU admission with those who did not. Results: Among the 242 patients hospitalized during the defined period of time, 44 (18.2%) needed ICU admission. Forty (16.5%) patients died during hospital admission. Two hundred and two (83.5%) patients were discharged alive from the hospital. At six months, 183 (75.6%) patients completed the questionnaires (32 ICU patients and 151 non ICU patients). Ninety-six (52.4%) reported decreased quality of life and 143 (78.1%) described persistent symptoms. More ICU patients showed worsening of their quality of life (71.9 vs. 43.7%, P = 0.004). There were no differences in the proportion of patients with persistent symptoms between ICU and non ICU patients (87.5 vs. 76.2%, P = 0.159). ICU patients showed more frequently dyspnea on exertion (78.1 vs. 47.7%, P = 0.02), dyspnea on light exertion (37.5 vs. 4.6%, P < 0.001), and asthenia (56.3 vs. 29.1, P = 0.003). Conclusions: Survivors of COVID-19 needing hospitalization had persistent symptoms and a decline in the quality of life. ICU patients referred a large decrease of their quality of life compared with non ICU patients.

10.
Rev Clin Esp ; 211(1): 1-8, 2011 Jan.
Artigo em Espanhol | MEDLINE | ID: mdl-21196002

RESUMO

OBJECTIVE: The achievement of the therapeutic objectives in patients with ischemic heart disease and metabolic syndrome is unknown. This study has aimed to evaluate whether the prevalence of risk factors, the prescription rate of evidence-based cardiovascular therapies and the attainment of therapeutic goals differ in coronary patients with and without the metabolic syndrome (MS). METHODS: A multicenter, cross-sectional study carried out with the participation of 7,600 patients with stable coronary heart disease (mean age 65.3 years, 82% males, 37.7% with MS) attended in primary care. Data on drug prescription and goal attainment were extracted from clinical records. MS was defined according to the National Cholesterol Education Program (NCEP) criteria. RESULTS: Patients with MS had a higher prevalence of cardiovascular risk factors and cardiovascular disease. They also had a higher prescription rate of blood-pressure lowering drugs, statins and antidiabetic agents, without differences in the rate of use of antithrombotics and beta-blockers. After adjusting for cardiovascular risk factors and co-morbidity, only fibrates and angiotensin II receptor blockers were used more frequently in MS patients. A lower percentage of subjects with MS achieved therapeutic goals of LDL cholesterol (23.4% vs 27.7%, P<.001), blood pressure (29.1% vs 52.2%, P<.001) and, in diabetics, of glycated hemoglobin (54.7% vs 75.9%, P<.001). CONCLUSION: Patients with stable coronary disease and MS do not reach therapeutic objectives as frequently as those without MS, in spite of receiving a higher amount of cardiovascular drugs.


Assuntos
Fármacos Cardiovasculares/uso terapêutico , Doença das Coronárias/complicações , Doença das Coronárias/tratamento farmacológico , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Idoso , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Estudos Transversais , Feminino , Humanos , Masculino , Prevalência , Fatores de Risco
11.
Artigo em Inglês | MEDLINE | ID: mdl-34353767

RESUMO

BACKGROUND AND GOAL OF THE STUDY: The goal of the study was to compare the incidence of complications, technical difficulty of intubation and physiologic pre-intubation status between the first intubation and reintubation performed on the same patient in an ICU. MATERIALS AND METHODS: The study was approved by the ethics committee of Galicia (Santiago-Lugo, code No. 2015-012). Due to the observational, noninterventional, and noninvasive design of this study, the need for written consent was waived by the ethics committee of Galicia. Patients requiring tracheal intubation and reintubation in the ICU were included in this prospective observational study. Main endpoint was to compare the incidence of complications, physiologic pre-intubation status, and the rate of technical difficulty of intubation between the first intubation and reintubation performed on the same patient in an ICU. RESULTS AND DISCUSSION: 504 patients were intubated in our ICU during the study period, and 82 (16%) required reintubation. There was no difference between the first intubation and reintubation regarding number of total complication (35% vs 33%; P = ,86), hypotension (24% vs 24%; P = 1), hypoxia (26% vs 26%; P = 1), esophageal intubation (1% vs 1%; P = 1), and bronchoaspiration (2% vs 1%; P = ,86). Physiologic pre-intubation status and technical difficulty of intubation did not differ between the first intubation and reintubation. CONCLUSIONS: In our ICU patients requiring tracheal reintubation, incidence of complications, physiologic pre-intubation status, and technical difficulty of intubation did not differ between the first intubation and reintubation.


Assuntos
Hipotensão , Intubação Intratraqueal , Humanos , Hipotensão/epidemiologia , Unidades de Terapia Intensiva , Intubação Intratraqueal/efeitos adversos , Estudos Prospectivos , Traqueia
12.
Rev Esp Anestesiol Reanim (Engl Ed) ; 68(1): 10-20, 2021 Jan.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33077309

RESUMO

BACKGROUND AND OBJECTIVES: There are limited information on outcome, complications and treatments of critically ill COVID-19 patients requiring admission to an intensive care unit (ICU). The aim of this study is to describe the clinical ICU course, treatments used, complications and outcomes, of critically ill COVID-19 patients admitted in seven ICU in Galicia region during the 2020 March-April pandemic peak. METHODS: Between March 21 and April 19, 2020, we evaluated critically ill COVID-19 patients admitted to the ICU of Anesthesia of seven hospitals in Galicia, northwestern Spain. Outcome, complications, and treatments were monitored until May 6, 2020, the final date of follow-up. RESULTS: A total of 97 critically ill COVID-19 patients were included. During ICU stay, mechanical ventilation became necessary in 80 (82.5%) patients, and tracheostomy in 22 (22.7%) patients. Prone position was used frequently in both intubated (67.5%) and awake (27.8%) patients. Medications consisted of antivirals agents (92.7%), corticosteroids (93.8%), tocilizumab (57.7%), and intermediate or high doses of anticoagulants (83.5%). The most frequent complications were ICU-acquired infection (52.6%), thrombosis events (16.5%), and reintubation (9.3%). After a median follow-up of 42 (34-45) days, 15 patients (15.5%) deceased, 73 patients (75.2%) had been discharged from ICU, and nine patients (9.3%) were still in the ICU. CONCLUSIONS: A high proportion of our critically ill COVID-19 patients required mechanical ventilation, prone positioning, antiviral medication, corticosteroids, and anticoagulants. ICU complications were frequent, mainly infections and thrombotic events. We had a relatively low mortality of 15,5%.


Assuntos
Anestesia , COVID-19 , Idoso , COVID-19/complicações , COVID-19/terapia , Cuidados Críticos , Estado Terminal , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Espanha
13.
Acta Anaesthesiol Scand ; 54(2): 241-5, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19735494

RESUMO

BACKGROUND: Both multiple injection and single posterior cord injection techniques are associated with extensive anesthesia of the upper limb after an infraclavicular coracoid block (ICB). The main objective of this study was to directly compare the efficacy of both techniques in terms of the rates of completely anesthetizing cutaneous nerves below the elbow. METHODS: Seventy patients undergoing surgery at or below the elbow were randomly assigned to receive an ICB after the elicitation of either a single radial nerve-type response (Radial group) or of two different main nerve-type responses of the upper limb, except for the radial nerve (Dual group). Forty milliliters of 1.5% mepivacaine was given in a single or a dual dose, according to group assignment. The sensory block was assessed in each of the cutaneous nerves at 10, 20 and 30 min. Block performance times and the rates of complete anesthesia below the elbow were also noted. RESULTS: Higher rates of sensory block of the radial nerve were found in the Radial group at 10, 20 and 30 min (P<0.05). The rates of sensory block of the ulnar nerve at 30 min were 97% and 75% in the Radial and in the Dual groups, respectively (P<0.05). The rate of complete anesthesia below the elbow was also higher in the Radial group at 30 min (P<0.05). CONCLUSIONS: Injection of a local anesthetic after a single stimulation of the radial nerve fibers produced more extensive anesthesia than using a dual stimulation technique under the conditions of our study.


Assuntos
Antebraço/inervação , Bloqueio Nervoso/métodos , Escápula , Anestésicos Locais/administração & dosagem , Plexo Braquial/efeitos dos fármacos , Cotovelo/inervação , Estimulação Elétrica/instrumentação , Feminino , Mãos/inervação , Humanos , Injeções/instrumentação , Masculino , Nervo Mediano/efeitos dos fármacos , Mepivacaína/administração & dosagem , Pessoa de Meia-Idade , Nervo Musculocutâneo/efeitos dos fármacos , Bloqueio Nervoso/instrumentação , Fibras Nervosas/efeitos dos fármacos , Nervo Radial/efeitos dos fármacos , Fatores de Tempo , Nervo Ulnar/efeitos dos fármacos , Punho/inervação
14.
Xenobiotica ; 39(6): 444-56, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19480550

RESUMO

ZD4054 is an oral specific endothelin-A receptor antagonist in development for the treatment of hormone-resistant prostate cancer. Both renal and metabolic processes contribute to its overall clearance. Two preclinical in vitro studies investigated the metabolism of ZD4054 using human liver microsomes, individual cytochrome P450 (CYP) isozymes, and flavin-containing monooxygenase isoforms. Two Phase I open-label crossover volunteer studies subsequently investigated in vivo drug interactions between ZD4054 and the CYP450 inducer rifampicin or CYP3A4 inhibitor itraconazole. The most abundant metabolite produced in in vitro incubations accounted for 12.8% of radioactivity after ZD4054 was incubated with CYP3A4. No significant flavin-containing monooxygenase metabolism of ZD4054 was observed. In the in vivo studies, rifampicin co-administration reduced the area under the concentration-time curve and maximum plasma concentration of ZD4054 by 68% and 29%, respectively, whilst co-administration with itraconazole was associated with an increase in ZD4054 area under the curve of approximately 28%. While co-administration of CYP450 inducers might be associated with reduced efficacy of ZD4054, dose reduction is unlikely to be required with concomitant administration of CYP3A4 inhibitors.


Assuntos
Antagonistas do Receptor de Endotelina A , Saúde , Itraconazol/farmacologia , Pirrolidinas/metabolismo , Rifampina/farmacologia , Adolescente , Adulto , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacocinética , Cromatografia Líquida de Alta Pressão , Sistema Enzimático do Citocromo P-450/metabolismo , Demografia , Avaliação Pré-Clínica de Medicamentos , Interações Medicamentosas , Feminino , Humanos , Itraconazol/administração & dosagem , Masculino , Pessoa de Meia-Idade , Oxigenases/metabolismo , Pirrolidinas/efeitos adversos , Pirrolidinas/química , Pirrolidinas/farmacocinética , Rifampina/administração & dosagem
15.
Rev Esp Anestesiol Reanim (Engl Ed) ; 66(9): 487-489, 2019 Nov.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31353038

RESUMO

We report a case of Pseudomonas monteilii and Acinetobacter nosocomialis endocarditis with a fatal outcome in a patient with a recent history of prosthetic aortic valve replacement. Transesophageal echocardiography and computed tomography confirmed the presence of vegetation on the prosthetic valve and aortic pseudoaneurism with an aortic root abscess. Valve cultures yielded P.monteilii and A.nosocomialis. The patient underwent surgery and received antibiotics, but his condition deteriorated and he died 44days after surgery. To our knowledge, this is the first case of P.monteilii and A.nosocomialis endocarditis reported in the literature. These organisms have been described as environmental contaminants; however, they must be considered potential pathogens, particularly in patients with prosthetic valves.


Assuntos
Abscesso/microbiologia , Infecções por Acinetobacter/microbiologia , Endocardite/microbiologia , Próteses Valvulares Cardíacas/microbiologia , Infecções Relacionadas à Prótese/microbiologia , Infecções por Pseudomonas/microbiologia , Acinetobacter/isolamento & purificação , Idoso , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/microbiologia , Aneurisma Infectado/diagnóstico por imagem , Aneurisma Infectado/microbiologia , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/cirurgia , Estenose da Valva Aórtica/cirurgia , Evolução Fatal , Humanos , Masculino , Pseudomonas/isolamento & purificação
16.
Sci Total Environ ; 661: 531-542, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30682606

RESUMO

Assuming a steady state between carbon (C) gains and losses, greenhouse gases (GHG) inventories that follow a widely used simplified procedure (IPCC Tier 1) tend to underestimate the capacity of soils in grazing-land to sequester C. In this study we compared the C balance reported by (i) national inventories that followed the simplified method (Tier 1) of IPCC (1996/2006), with (ii) an alternative estimation derived from the meta-analysis of science-based, peer-reviewed data. We used the global databases (i) EDGAR 4.2 to get data on GHG emissions due to land conversion and livestock/crop production, and (ii) HYDE 3.1 to obtain historical series on land-use/land cover (LULC). In terms of sequestration, our study was focused on C storage as soil organic carbon (SOC) in rural lands of four countries (Argentina, Brazil, Paraguay and Uruguay) within the so-called MERCOSUR region. Supported by a large body of scientific evidence, we hypothesized that C gains and losses in grazing lands are not in balance and that C gains tend to be higher than C losses at low livestock densities. We applied a two-way procedure to test our hypothesis: i) a theoretical one based on the annual conversion of belowground biomass into SOC; and ii) an empirical one supported by peer-reviewed data on SOC sequestration. Average figures from both methods were combined with LULC data to reassess the net C balance in the study countries. Our results show that grazing lands generate C surpluses that could not only offset rural emissions, but could also partially or totally offset the emissions of non-rural sectors. The potential of grazing lands to sequester and store soil C should be reconsidered in order to improve assessments in future GHG inventory reports.


Assuntos
Sequestro de Carbono , Carbono/análise , Pradaria , Solo/química , Argentina , Brasil , Paraguai , Uruguai
17.
Rev Esp Anestesiol Reanim (Engl Ed) ; 66(5): 250-258, 2019 May.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30862397

RESUMO

BACKGROUND AND OBJECTVIES: Tracheal intubation in the Intensive Care Unit is associated with a high incidence of difficult intubation and complications. This may be due to a poor view of the glottis during direct laryngoscopy. The aim of this study is to determine if there is a relationship between laryngoscopy view using the modified Cormack-Lehane scale with the incidence of difficult intubation and complications. METHODS: All patients who were subjected to tracheal intubated with direct laryngoscopy in the Intensive Care Unit over a 45 month period were included in the study. In all patients, an evaluation was made of the laryngoscopy view using the modified Cormack-Lehane scale, as well as the technical difficulty (number of intubations at first attempt, operator-reported difficulty, need for a Frova introducer), and the incidence of complications (hypotension, hypoxia, oesophageal intubation). RESULTS: A total of 360 patients were included. When the grade of the modified Cormack-Lehane scale was increased from 1 to 4, the incidence of first success rate intubation decreased (1: 97%, 2a: 94%, 2b: 80%, 3: 60%, 4: 0%, p<.001), the incidence of moderate and severe difficulty intubation increased (1: 2%, 2a: 4%, 2b: 36%, 3: 77%, 4: 100%, p<.001.), as well as the need for a Frova guide (1: 7%, 2a: 8%, 2b: 45%, 3: 60%, 4: 100%, p<.001). When the grade of the modified Cormack-Lehane scale increased from 1 to 4, the incidence of hypoxia<90% increased (1: 20%, 2a: 20%, 2b: 28%, 3: 47%, 4: 100%, p=.0073), as well as hypoxia<80% (1: 11%, 2a: 10%, 2b: 12%, 3: 27%, 4: 100%, p=.00398). No relationship was observed between the incidence of hypotension and the grade of the modified Cormack-Lehane scale (p=ns). CONCLUSIONS: During tracheal intubation in the Intensive Care Unit a close relationship was found between a poor laryngoscopy view using the modified Cormack-Lehane scale and a higher difficulty technique of intubation. A relationship was found between the incidence of hypoxia with a higher grade in the modified Cormack-Lehane scale. No relationship was found between hypotension and the modified Cormack-Lehane scale.


Assuntos
Unidades de Terapia Intensiva , Intubação Intratraqueal/métodos , Laringoscopia , Idoso , Idoso de 80 Anos ou mais , Esôfago , Feminino , Glote , Humanos , Hipotensão/etiologia , Hipóxia/etiologia , Intubação Intratraqueal/efeitos adversos , Laringoscopia/métodos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
18.
Med Intensiva (Engl Ed) ; 42(9): 527-533, 2018 Dec.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29275003

RESUMO

OBJECTIVE: To compare the complications and the difficulty of orotracheal intubation procedures performed in the Intensive Care Unit during the off-hours period and the on-hours period. DESIGN: A prospective, observational and non-interventional cohort study covering a period of 27 months was carried out. Working days between 8:00 a. m. and 7:59 p. m. were considered «on-hours¼, while the remaining shifts were regarded as «off-hours¼. SCOPE: An 18-bed surgical in a Intensive Care Unit of a third-level hospital. PATIENTS: All orotracheal intubation patients admitted to the ICU from January 2015 to March 2017 were included. Patients were stratified into 2groups according to whether intubation was performed on-hours or off-hours. INTERVENTIONS: Non-interventional study. VARIABLES OF INTEREST: The reason for intubation, time and day on which intubation was performed, degree of intubation difficulty (number of attempts, Cormack-Lehane laryngoscopic vision, need for accessory material) and complications during intubation. RESULTS: A total of 252 patients were intubated; of these, 132 were included in the on-hours group and 120 patients in the off-hours group. In the off-hours group we observed a greater percentage of urgent and emergent intubations compared to the on-hours group. However, no differences were found between the 2groups in relation to the other variables studied. CONCLUSIONS: During the off-hours period, orotracheal intubation was not associated to a greater number of complications or to greater difficulty of the technique in our Unit.


Assuntos
Plantão Médico , Hipotensão/etiologia , Hipóxia/etiologia , Unidades de Terapia Intensiva , Intubação Intratraqueal/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Manuseio das Vias Aéreas , Grupos Diagnósticos Relacionados , Feminino , Humanos , Hipotensão/epidemiologia , Hipóxia/epidemiologia , Unidades de Terapia Intensiva/organização & administração , Laringoscopia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Tamanho da Amostra , Centros de Atenção Terciária
20.
Rev. esp. anestesiol. reanim ; 69(6): 326-335, Jun - Jul 2022. tab, graf
Artigo em Espanhol | IBECS (Espanha) | ID: ibc-205067

RESUMO

Antecedentes/contexto: Existe una tendencia en los pacientes hospitalizados por COVID-19 a desarrollar síntomas persistentes y a presentar una disminución en su calidad de vida tras el ingreso hospitalario. Métodos: Estudio de cohorte prospectivo de pacientes con COVID-19 con ingreso hospitalario entre el 1 de marzo al 30 de abril de 2020. El objetivo primario fue comparar la calidad de vida relacionada con la salud y la presencia de síntomas persistentes seis meses después del ingreso, comparando los pacientes que requirieron ingreso en UCI con los que no lo precisaron. Resultados: De los 242 pacientes hospitalizados durante el período de estudio, 44 (18,2%) necesitaron ingreso en UCI. Cuarenta (16,5%) pacientes fallecieron durante el ingreso hospitalario. Doscientos dos (83,5%) pacientes fueron dados de alta del hospital. A los seis meses, 183 (75,6%) pacientes completaron los cuestionarios (32 pacientes UCI y 151 pacientes no UCI). Noventa y seis (52,4%) refirieron disminución de la calidad de vida y 143 (78,1%) describieron síntomas persistentes. Un número mayor de pacientes de UCI mostraron un empeoramiento de su calidad de vida (71,9 vs. 43,7%, p = 0,004). No hubo diferencias en la proporción de pacientes con síntomas persistentes entre los pacientes con UCI y sin UCI (87,5 vs. 76,2%, p = 0,159). Los pacientes de UCI mostraron con mayor frecuencia disnea de esfuerzo (78,1 vs. 47,7%, p = 0,02), disnea de pequeños esfuerzos (37,5 vs. 4,6%, p < 0,001) y astenia (56,3 vs. 29,1%, p = 0,003). Conclusiones: Los supervivientes de COVID-19 que necesitaron hospitalización presentaron síntomas persistentes y un deterioro de su calidad de vida. Los pacientes de UCI refirieron una mayor disminución de su calidad de vida, en comparación con los pacientes que no precisaron UCI.(AU)


Background: Hospitalized COVID-19 patients are prone to develop persistent symptoms and to show reduced quality of life following hospital admission. Methods: Prospective cohort study of COVID-19 patients admitted to a hospital from March 1 to April 30, 2020. The primary outcome was to compare health related quality of life and persistent symptoms six months after hospital admission, of COVID-19 patients who required ICU admission with those who did not. Results: Among the 242 patients hospitalized during the defined period of time, 44 (18.2%) needed ICU admission. Forty (16.5%) patients died during hospital admission. Two hundred and two (83.5%) patients were discharged alive from the hospital. At six months, 183 (75.6%) patients completed the questionnaires (32 ICU patients and 151 non ICU patients). Ninety-six (52.4%) reported decreased quality of life and 143 (78.1%) described persistent symptoms. More ICU patients showed worsening of their quality of life (71.9 vs. 43.7%, P = 0.004). There were no differences in the proportion of patients with persistent symptoms between ICU and non ICU patients (87.5 vs. 76.2%, P = 0.159). ICU patients showed more frequently dyspnea on exertion (78.1 vs. 47.7%, P = 0.02), dyspnea on light exertion (37.5 vs. 4.6%, P < 0.001), and asthenia (56.3 vs. 29.1, P = 0.003). Conclusions: Survivors of COVID-19 needing hospitalization had persistent symptoms and a decline in the quality of life. ICU patients referred a large decrease of their quality of life compared with non ICU patients.(AU)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Qualidade de Vida , Estudos Prospectivos , Pacientes Internados , Unidades de Terapia Intensiva , Betacoronavirus , Pandemias , Hospitalização , Estudos de Coortes , Doenças Transmissíveis , Doenças Respiratórias , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave
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