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BACKGROUND: Although high-density lipoprotein (HDL) has atheroprotective properties, the association of HDL functionality with coronary plaques remains unclear. METHODS: We investigated the association between HDL-mediated cholesterol efflux capacity (CEC) and coronary lipid burden in 74 patients who underwent near-infrared spectroscopy (NIRS) imaging for acute coronary syndrome (ACS) or stable ischemic symptoms. We measured baseline HDL-mediated CEC, distinguishing the specific pathways, and stratified patients according to their median CEC values. Coronary lipid burden was assessed as lipid core burden index (LCBI) using NIRS at baseline (n=74) and on serial imaging (n=47). RESULTS: Patients with baseline ATP-binding cassette transporter G1 (ABCG1)-mediated CEC > median had a greater baseline LCBI {74 [20, 128] vs. 32 [5, 66]; P=0.04} or change in LCBI {-30 [-89, 0] vs. -3 [-16, 0]; P=0.048}. In addition to a negative association between baseline LCBI and change in LCBI (standardized ß=-0.31; P=0.02), multivariable analysis demonstrated a significant interaction effect between clinical presentation of coronary artery disease (CAD) and baseline ABCG1-mediated CEC on change in LCBI (P=0.003), indicating that baseline ABCG1-mediated CEC was inversely associated with change in LCBI in patients with ACS (standardized ß=-0.79, P=0.003), but not in those with stable ischemic symptoms (P=0.52). CONCLUSIONS: In this study, ABCG1-mediated CEC, but not ATP-binding cassette transporter A1 and scavenger receptor B type I, was associated with regression of coronary artery lipid content, especially in patients with high-risk phenotype. Further studies are required to determine the roles of ABCG1 pathway in the development coronary plaques.
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OBJECTIVES: To examine economic evaluation studies of stem cell therapies (SCTs) in neurological disorders and to provide an overview of the quality of the economic evidence available on this topic. METHODS: The review examined studies that performed an economic evaluation of the use of stem cells in adult patients with neurological diseases and that were published in English during the period 2007 to 2017. Data analyzed and reported included study population, disease indication, main analytical approaches for the economic analysis and perspective, key assumptions made or tested in sensitivity analyses, cost outcomes, estimates of incremental cost effectiveness, and approaches to quantifying decision uncertainty. RESULTS: A total of three studies reporting on the findings of the economic evaluation of the use of SCT in stroke, Parkinson disease, and secondary progressive multiple sclerosis, respectively, were identified. All three studies conducted a cost-utility analysis using decision-analytic models and reported an incremental cost per quality-adjusted life-years gained (incremental cost-effectiveness ratio) versus standard care. These studies reported meaningful cost savings in stroke, Parkinson disease, and secondary progressive multiple sclerosis in the base-case scenarios. CONCLUSIONS: Despite significant progress in clinical research in the use of SCT in neurological diseases, economic evaluation of these therapies is still at a nascent stage. Given the early stage of research inputs (clinical and cost outcomes data) into the models per se, further research is urgently needed to enable meaningful assessment of the cost effectiveness of these advanced therapies and to ensure sustainable access for population groups most likely to benefit in clinical practice.
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Análise Custo-Benefício/métodos , Doenças do Sistema Nervoso/economia , Doenças do Sistema Nervoso/terapia , Transplante de Células-Tronco/economia , Humanos , Doenças do Sistema Nervoso/epidemiologia , Transplante de Células-Tronco/métodos , Avaliação da Tecnologia Biomédica/economia , Avaliação da Tecnologia Biomédica/métodosRESUMO
BACKGROUND: Apabetalone is a selective bromodomain and extra-terminal (BET) inhibitor which modulates lipid and inflammatory pathways implicated in atherosclerosis. The impact of apabetalone on attenuated coronary atherosclerotic plaque (AP), a measure of vulnerability, is unknown. METHODS: The ApoA-1 Synthesis Stimulation and intravascular Ultrasound for coronary atheroma Regression Evaluation (ASSURE; NCT01067820) study employed serial intravascular ultrasound (IVUS) measures of coronary atheroma in 281 patients treated with apabetalone or placebo for 26 weeks. AP was measured at baseline and follow-up. Factors associated with changes in AP were investigated. RESULTS: AP was observed in 31 patients (11%) [27 (13.0%) in the apabetalone group and four (5.5%) in the placebo group]. The apabetalone group demonstrated reductions in AP length by - 1 mm [interquartile range (IQR) - 4, 1] (p = 0.03), AP arc by - 37.0° (IQR - 59.2, 8.2) (p = 0.003) and the AP index by - 34.6 mm° (IQR - 52.6, 10.1) (p = 0.003) from baseline. The change in AP index correlated with on-treatment concentration of high-density lipoprotein (HDL) particles (r = - 0.52, p = 0.006), but not HDL cholesterol (r = - 0.11, p = 0.60) or apolipoprotein A-1 (r = - 0.16, p = 0.43). Multivariable analysis revealed that on-treatment concentrations of HDL particles (p = 0.03) and very low-density lipoprotein particles (p = 0.01) were independently associated with changes in AP index. CONCLUSIONS: Apabetalone favorably modulated ultrasonic measures of plaque vulnerability in the population studied, which may relate to an increase in HDL particle concentrations. The clinical implications are currently being investigated in the phase 3 major adverse cardiac event outcomes trial BETonMACE.
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Aterosclerose/tratamento farmacológico , Doença da Artéria Coronariana/tratamento farmacológico , Placa Aterosclerótica/tratamento farmacológico , Quinazolinonas/uso terapêutico , Idoso , Apolipoproteína A-I/metabolismo , Aterosclerose/metabolismo , HDL-Colesterol/metabolismo , Angiografia Coronária/efeitos dos fármacos , Doença da Artéria Coronariana/metabolismo , Método Duplo-Cego , Feminino , Coração/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/metabolismo , Estudos ProspectivosRESUMO
Importance: CER-001 is a negatively charged, engineered pre-ß high-density lipoprotein (HDL) mimetic containing apolipoprotein A-I and sphingomyelin. Preliminary studies demonstrated favorable effects of CER-001 on cholesterol efflux and vascular inflammation. A post hoc reanalysis of a previously completed study of intravenous infusion of CER-001, 3 mg/k, showed that the intravenous infusion in patients with a high coronary plaque burden promoted regression as assessed by intravascular ultrasonography. Objective: To determine the effect of infusing CER-001 on coronary atherosclerosis progression in statin-treated patients. Design, Setting, and Participants: A double-blind, randomized, multicenter trial evaluating the effect of 10 weekly intravenous infusions of CER-001, 3 mg/kg, (n = 135) or placebo (n = 137) in patients with an acute coronary syndrome (ACS) and baseline percent atheroma volume (PAV) greater than 30% in the proximal segment of an epicardial artery by intravascular ultrasonography. The study included 34 academic and community hospitals in Australia, Hungary, the Netherlands, and the United States in patients with ACS presenting for coronary angiography. Patients were enrolled from August 15, 2015, to November 19, 2016. Interventions: Participants were randomized to receive weekly CER-001, 3 mg/kg, or placebo for 10 weeks in addition to statins. Main Outcomes and Measures: The primary efficacy measure was the nominal change in PAV from baseline to day 78 measured by serial intravascular ultrasonography imaging. The secondary efficacy measures were nominal change in normalized total atheroma volume and percentage of patients demonstrating plaque regression. Safety and tolerability were also evaluated. Results: Among 293 patients (mean [SD] age, 59.8 [9.4] years; 217 men [79.8%] and 261 white race/ethnicity [96.0%]), 86 (29%) had statin prior use prior to the index ACS and 272 (92.8%) had evaluable imaging at follow-up. The placebo and CER-001 groups had similar posttreatment median levels of low-density lipoprotein cholesterol (74 mg/dL vs 79 mg/dL; P = .15) and high-density lipoprotein cholesterol (43 mg/dL vs 44 mg/dL; P = .66). The primary efficacy measure, PAV, decreased 0.41% with placebo (P = .005 compared with baseline), but not with CER-001 (-0.09%; P = .67 compared with baseline; between group differences, 0.32%; P = .15). Similar percentages of patients in the placebo and CER-001 groups demonstrated regression of PAV (57.7% vs 53.3%; P = .49). Infusions were well tolerated, with no differences in clinical and laboratory adverse events observed between treatment groups. Conclusions and Relevance: Infusion of CER-001 did not promote regression of coronary atherosclerosis in statin-treated patients with ACS and high plaque burden. Trial Registration: ClinicalTrials.gov Identifier: NCT2484378.
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Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/tratamento farmacológico , Apolipoproteína A-I/administração & dosagem , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Fosfolipídeos/administração & dosagem , Proteínas Recombinantes/administração & dosagem , Idoso , Apolipoproteína A-I/uso terapêutico , Austrália , Progressão da Doença , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Hungria , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Bombas de Infusão , Masculino , Pessoa de Meia-Idade , Países Baixos , Fosfolipídeos/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Resultado do Tratamento , Ultrassonografia de Intervenção , Estados UnidosRESUMO
BACKGROUND AND AIMS: Wall shear stress (WSS) has an important role in the natural history of coronary atherosclerosis. The aim of this study is to investigate the relationship between WSS and the lipid content of atherosclerotic plaques as assessed by near-infrared spectroscopy (NIRS). METHODS: We performed serial NIRS and intravascular ultrasound (IVUS) upon Doppler coronary flow guidewire of coronary plaques at baseline and after 12-18 months in 28 patients with <30% angiographic stenosis, who presented with coronary artery disease. Segmental WSS, plaque burden and NIRS-derived lipid rich plaque (LRP) were evaluated at both time-points in 482 consecutive 2-mm coronary segments. RESULTS: Segments with LRP at baseline (nâ¯=â¯106) had a higher average WSS (1.4⯱â¯0.6â¯N/m2), compared to those without LRP (nâ¯=â¯376) (1.2⯱â¯0.6â¯N/m2, p<0.001). In segments without baseline LRP, WSS was higher in those who subsequently developed new LRP (nâ¯=â¯35) than those who did not (nâ¯=â¯341) (1.4⯱â¯0.8 vs. 1.1⯱â¯0.6â¯N/m2, p=0.002). Conversely, in segments with baseline LRP, WSS was lower in those who had regression of lipid content (nâ¯=â¯41) than those who did not (nâ¯=â¯65) (1.2⯱â¯0.4 vs. 1.6⯱â¯0.7â¯N/m2, p=0.007). Segments with the highest tertile of WSS displayed greater progression of LCBI irrespective of baseline lipid content (p<0.001). Multivariate analysis revealed that baseline WSS (p=0.017), PAV (p<0.001) and LCBI (p<0.001) were all independent predictors of change in LCBI over time. CONCLUSIONS: Coronary segments with high WSS associate with progression of lipid content over time, which may indicate transformation to a more vulnerable phenotype.
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Doença da Artéria Coronariana/diagnóstico por imagem , Estenose Coronária/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Metabolismo dos Lipídeos , Placa Aterosclerótica , Espectroscopia de Luz Próxima ao Infravermelho , Idoso , Velocidade do Fluxo Sanguíneo , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/terapia , Circulação Coronária , Estenose Coronária/metabolismo , Estenose Coronária/patologia , Estenose Coronária/terapia , Vasos Coronários/metabolismo , Vasos Coronários/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Prognóstico , Ruptura Espontânea , Índice de Gravidade de Doença , Estresse Mecânico , Fatores de Tempo , Ultrassonografia de IntervençãoRESUMO
BACKGROUND: Inhibition of bromodomain and extra-terminal (BET) proteins can modulate lipoprotein and inflammatory factors that mediate atherosclerosis. The impact of the BET inhibitor, apabetalone, on cardiovascular events is unknown. OBJECTIVE: Our objective was to investigate the impact of apabetalone on cardiovascular event rates in a pooled analysis of clinical studies in patients with established coronary artery disease. METHODS: We conducted a pooled analysis of patients (n = 798) with coronary artery disease who participated in clinical trials (ASSERT, ASSURE, SUSTAIN) that evaluated the impact of 3-6 months of treatment with apabetalone on lipid parameters and coronary atherosclerosis. The incidence of major adverse cardiovascular events (death, myocardial infarction, coronary revascularization, hospitalization for cardiovascular causes) in the treatment groups was evaluated. RESULTS: At baseline, patients treated with apabetalone were more likely to be Caucasian, have a history of dyslipidemia, and be undertreated with ß-blocker and anti-platelet agents. Treatment with apabetalone produced the following dose-dependent changes compared with placebo: increases in apolipoprotein A-I (apoA-I) of up to 6.7% (P < 0.001), increases in high-density lipoprotein cholesterol (HDL-C) of up to 6.5% (P < 0.001), increases in large HDL particles of up to 23.3% (P < 0.001), and decreases in high-sensitivity C-reactive protein (hsCRP) of - 21.1% (P = 0.04). Apabetalone treatment did not affect atherogenic lipoproteins compared with placebo. Patients treated with apabetalone experienced fewer major adverse cardiovascular events than those treated with placebo (5.9 vs. 10.4%; P = 0.02), a finding that was more prominent in patients with diabetes (5.4 vs. 12.7%; P = 0.02), with baseline HDL-C < 39 mg/dl (5.5 vs. 12.8%; P = 0.01), or with elevated hsCRP levels (5.4 vs. 14.2%; P = 0.02). CONCLUSION: Pooled analysis of short-term studies demonstrated fewer cardiovascular events among patients treated with the BET protein inhibitor, apabetalone, than among those treated with placebo. BET protein inhibition warrants further investigation as a novel approach to cardiovascular risk reduction.
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Doenças Cardiovasculares/induzido quimicamente , Sistema Cardiovascular/efeitos dos fármacos , Doença da Artéria Coronariana/tratamento farmacológico , Proteínas/antagonistas & inibidores , Anticolesterolemiantes/uso terapêutico , Aterosclerose/metabolismo , Proteína C-Reativa/metabolismo , Doenças Cardiovasculares/metabolismo , Sistema Cardiovascular/metabolismo , HDL-Colesterol , Ensaios Clínicos como Assunto , Doença da Artéria Coronariana/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RiscoRESUMO
BACKGROUND AND AIMS: Little is known about the relation between serum lipid parameters and serial change in plaque composition using in vivo coronary imaging. The aim of this study was to examine the association between serum lipids and change in coronary plaque lipid burden assessed by near-infrared spectroscopy (NIRS). METHODS: We performed serial NIRS-intravascular ultrasound studies in 49 patients who underwent coronary angiography for an acute coronary syndrome (ACS) or stable ischemic symptoms. Univariable and multivariable linear regression analyses were applied to evaluate the relationship between serum lipid parameters and change in lipid core burden index at the 4-mm maximal segment (max LCBI4mm). RESULTS: Mean patient age was 61 ± 9 y, 29% were women, 35% had an ACS clinical presentation, 78% received statin therapy at baseline, and median low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), total cholesterol and triglyceride levels were 101, 43, 174 and 133 mg/dL, respectively. During a median follow-up period of 13 months, max LCBI4mm significantly decreased from 277 to 194 (p = 0.001). On univariable analysis, the percent change in HDL-C negatively associated with the change in max LCBI4mm (ß = -3.19, p = 0.004). There were no significant associations between the other lipid parameters and change in max LCBI4mm. On multivariable analysis, percent change in HDL-C remained significantly associated with the change in max LCBI4mm (p = 0.002). CONCLUSIONS: Change in HDL-C, but not other lipids parameters, associated with changes in coronary plaque lipid burden assessed by NIRS. These findings highlight the potential therapeutic importance of high-density lipoprotein on serial change in plaque composition.
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Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico por imagem , HDL-Colesterol/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Placa Aterosclerótica , Espectroscopia de Luz Próxima ao Infravermelho , Ultrassonografia de Intervenção , Síndrome Coronariana Aguda/patologia , Idoso , Biomarcadores/sangue , Distribuição de Qui-Quadrado , Angiografia Coronária , Doença da Artéria Coronariana/patologia , Vasos Coronários/patologia , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Shoulder impingement syndrome (SIS) is a common diagnosis for patients with pain and dysfunction of the shoulder. Variations in the signs and symptoms might lead to uncertainty regarding the definition of SIS. The aim of this review is to explore the participant selection criteria used in the literature when investigating SIS and to assess differences in criteria among treating professions. METHODS: This is a PRISMA systematic review of publications from 2009 to 2014 from MEDLINE, PubMed, The Cochrane Library, Embase, Scopus and CINAHL. RESULTS: Ninety-seven articles met inclusion criteria for this review. Twenty-five different surgical and nonsurgical treatments were investigated. Impingement-specific index tests were used in all studies. Exclusion index tests were used in 62% of studies. Twenty index tests were identified. Radiological investigations were reported in 53% of all studies, of which a further 53% reported using two or more radiological investigations. CONCLUSIONS: This systematic review has illustrated that studies investigating SIS test for various signs and symptoms, which is in keeping with describing the condition as a 'syndrome'. However, there are inconsistencies in participant selection criteria between health disciplines, highlighting a need for harmonization of the selection criteria in the form of an international editorial consensus.
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BACKGROUND: Preoperative anemia is a significant predictor of perioperative erythrocyte transfusion in elective arthroplasty patients. However, interactions with other patient and procedure characteristics predicting transfusion requirements have not been well studied. METHODS: Patients undergoing elective primary total hip arthroplasty or total knee arthroplasty at a tertiary hospital in Adelaide, South Australia, Australia, from January 2010 to June 2014 were used to identify preoperative predictors of perioperative transfusion. A logistic regression model was developed and externally validated with an independent data set from three other hospitals in Adelaide. RESULTS: Altogether, 737 adult patients in the derivation group and 653 patients in the validation group were included. Binary logistic regression modeling identified preoperative hemoglobin (odds ratio, 0.51; 95% CI, 0.43 to 0.59; P < 0.001 for each 1 g/dl increase), total hip arthroplasty (odds ratio, 3.56; 95% CI, 2.39 to 5.30; P < 0.001), and females 65 yr of age and older (odds ratio, 3.37; 95% CI, 1.88 to 6.04; P = 0.01) as predictors of transfusion in the derivation cohort. CONCLUSIONS: Using a combination of patient-specific preoperative variables, this validated model can predict transfusion in patients undergoing elective hip and knee arthroplasty. The model may also help to identify patients whose need for transfusion may be decreased through preoperative hemoglobin optimization.
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Artroplastia de Quadril , Artroplastia do Joelho , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Procedimentos Cirúrgicos Eletivos , Transfusão de Eritrócitos/estatística & dados numéricos , Assistência Perioperatória/estatística & dados numéricos , Idoso , Feminino , Humanos , Masculino , Razão de Chances , Austrália do SulRESUMO
BACKGROUND: The primary purpose of this systematic review was to clarify and quantify scoring system utilization in knee arthroplasty literature. In addition, the study considered the frequency and relationship of score use in articles published across a range of orthopedic journals, and the influence of study design, level of evidence, primary research topic, and study country of origin on the scoring system used. METHODS: A systematic search of 8 electronic databases was performed to identify publications of clinical studies involving knee arthroplasty, in which a scoring system was used to assess patient outcomes. RESULTS: Of the 1994 unique publications identified, 438 met the selection criteria. Identified articles reported a total of 86 scoring systems, 5 of which were reported in greater than 10.0% of included studies. The 1989 Knee Society Score was markedly the most utilized scoring system (58.7%). Use of the Knee Society Score was significantly associated with orthopedic journal impact factor (IF; P = .001), with greater use observed in journals of lower IF. Use of the Western Ontario and McMaster Universities Osteoarthritis Index escalated with increasing IF; however, no statistically significant association was observed. A preference for scoring systems developed in the country of residence of the first author was also identified. CONCLUSIONS: A large number of scoring systems are used to assess knee arthroplasty patients; however, 5 scores are consistently reported. By identifying and quantifying scoring system use, this review hopes to stimulate regularity in score usage to allow for improvements in comparability of clinician and patient-reported outcome measures in the knee arthroplasty literature.
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Artroplastia do Joelho , Índice de Gravidade de Doença , Humanos , Fator de Impacto de Revistas , Articulação do Joelho/cirurgia , Seleção de Pacientes , Resultado do TratamentoRESUMO
OBJECTIVE: Hand infections are a common presentation to health services in the Northern Territory; however, little is known about these patients. This study aims to identify incidence, treatment and co-morbidities of hand infection patients and to pinpoint factors associated with poor outcome. DESIGN: A retrospective study of all patients presenting to Alice Springs Hospital with a hand infection during 2012. SETTING: Orthopaedic Unit at Alice Springs Hospital. PARTICIPANTS: All patients admitted with a hand infection were included. MAIN OUTCOME MEASURES: Admission duration, duration waited before first presentation, re-admission rate, duration of re-admission and rate of methicillin-resistant Staphylococcus aureus. RESULTS: One hundred fourteen cases of hand infections were admitted to Alice Springs Hospital during 2012, of which 87 (76%) were in Indigenous patients. Indigenous patients (P = 0.001) and older patients (P = 0.038) had significantly longer admissions. Indigenous patients were 9.52 times (P = 0.038) more likely to be re-admitted than non-Indigenous patients. The rate of methicillin-resistant Staphylococcus aureus was 24.6%, and this was associated with smoking (P = 0.049) and substance abuse (P = 0.036). Formal follow-up was not related to indirect measures of hand infection severity, such as admission duration or re-admissions. CONCLUSION: Hand infections are a common presentation to Alice Springs Hospital. Indigenous people are admitted 2.38 times longer after adjusting for age and alcohol abuse. They have a more than ninefold chance of being re-admitted to hospital than non-Indigenous people following a hand infection.
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Mãos/microbiologia , Hospitais Rurais , Ortopedia , Infecções Estafilocócicas/epidemiologia , Adolescente , Adulto , Idoso , Austrália/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Masculino , Auditoria Médica , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Pessoa de Meia-Idade , Havaiano Nativo ou Outro Ilhéu do Pacífico , Estudos Retrospectivos , Staphylococcus aureus/isolamento & purificação , Streptococcaceae/isolamento & purificação , Adulto JovemRESUMO
OBJECTIVE: To determine whether short-term changes in liver tests (bilirubin, albumin, gamma glutamyl transferase, alkaline phosphatase, alanine aminotransferase (ALT) and aspartate aminotransferase) predict 12-month mortality and, if so, which test is most informative. DESIGN: Retrospective review of general medicine inpatients at a tertiary hospital (2005-2012) identified non-elective admissions of minimum 7â days' duration. Patients with liver disease, malignancy, admission to the intensive care unit or inpatient mortality were excluded. Linear spline modelled the vector of intra-admission change from admission. The association between 12-month mortality and admission and intra-admission changes in liver tests was assessed by logistic regression modelling, adjusted for age, gender, comorbidity index and heart failure. RESULTS: 12-month mortality was 17% in 4160 patients analysed. 12-month mortality for patients with abnormally low albumin at admission was 5% higher per 1â g/L below 34â g/L (OR 0.95, 95% CI 0.93 to 0.98, p<0.001). Albumin and ALT were the only tests for which an intra-admission change significantly predicted mortality; the predictive effects were additive. 12-month mortality was greater by 4% per 1â g/L intra-admission decrement in albumin (OR 1.04, 95% CI 1.02 to 1.06, p<0.001) and 6% per 100 IU/L intra-admission increment in ALT (OR 1.06, 95% CI 1.02 to 1.1, p=0.005). Intra-admission changes were superior to admission values in predicting mortality. CONCLUSIONS: Changes in liver tests predict long-term mortality better than a single value and provide prognostic information more quickly than long-term monitoring. In the absence of known liver disease, albumin predicts long-term mortality better than transaminases. The patient whose albumin decreases in the short term is at high risk of death within 1 year, even from a normal baseline.
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BACKGROUND: In acute liver failure (ALF) therapeutic plasma exchange (TPE) improves laboratory measures of liver function. In patients with ALF requiring minimal vasoactive support TPE has also been shown to provide haemodynamic benefits including an increase in systemic blood pressure. However the haemodynamic effects of TPE in patients with severe ALF requiring moderate or high dose vasopressor therapy has not been reported. We retrospectively examined the haemodynamic effects of TPE in a cohort of patients with severe ALF requiring vasopressor therapy. METHODS: Physiological, laboratory and treatment data were collected on all patients with ALF who received TPE between January 2000 and December 2012. All patients were managed in the intensive care unit of a tertiary referral centre for ALF and liver transplantation. The primary outcome measures were changes in mean arterial pressure (MAP), vasopressor score and the ratio of vasopressor score to MAP (vasopressor dependency index (VDI)) from baseline prior to TPE through to 12 hours after completion of TPE. Secondary outcome measures were changes in other routinely collected physiological variables and laboratory results. Results are presented as median (interquartile range (IQR)). Outcome measures were evaluated using a mixed effect model. RESULTS: Thirty nine TPE were performed in 17 patients with ALF (13 paracetamol poisoning). All TPE were performed with a centrifugal apheresis system (duration 130 minutes (IQR 115 - 147.5), plasma volume removed 5.1% body weight (IQR 4.6 - 5.5). Baseline values for primary outcome measures were: MAP 82 mmHg (IQR 72 - 92.5), vasopressor score 8.35 (IQR 3.62 - 24.6) and VDI 0.10 (IQR 0.05 - 0.31). MAP was significantly higher immediately after TPE compared to baseline (p = 0.039), however when corrected for change in vasopressor requirement there was no significant change in VDI with TPE (p = 0.953). Twelve hours after TPE the MAP, vasopressor score and VDI were not significantly different from baseline (p = 0.563, p = 0.317 and p = 0.214 respectively). CONCLUSION: In this cohort of patients with severe ALF centrifugal TPE did not significantly affect vasopressor requirements.
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Hemodinâmica/efeitos dos fármacos , Falência Hepática Aguda/tratamento farmacológico , Falência Hepática Aguda/terapia , Troca Plasmática , Vasoconstritores/uso terapêutico , Adulto , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVE: The present study aims to determine the importance of certain factors in predicting the need of hospital admission for a patient in the ED. METHODS: This is a retrospective observational cohort study between January 2010 and March 2012. The characteristics, including blood test results, of 100,123 patients who presented to the ED of a tertiary referral urban hospital, were incorporated into models using logistic regression in an attempt to predict the likelihood of patients' disposition on leaving the ED. These models were compared with triage nurses' prediction of patient disposition. RESULTS: Patient age, their initial presenting symptoms or diagnosis, Australasian Triage Scale category, mode of arrival, existence of any outside referral, triage time of day and day of the week were significant predictors of the patient's disposition (P < 0.001). The ordering of blood tests for any patient and the extent of abnormality of those tests increased the likelihood of admission. The accuracy of triage nurses' admission prediction was similar to that offered by a model that used the patients' presentation characteristics. The addition of blood tests to that model resulted in only 3% greater accuracy in prediction of patient disposition. CONCLUSIONS: Certain characteristics of patients as they present to hospital predict their admission. The accuracy of the triage nurses' prediction for disposition of patients is the same as that afforded by a model constructed from these characteristics. Blood test results improve disposition accuracy only slightly so admission decisions should not always wait for these results.
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Serviço Hospitalar de Emergência/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Medição de Risco/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália , Competência Clínica/normas , Feminino , Testes Hematológicos/estatística & dados numéricos , Humanos , Tempo de Internação/estatística & dados numéricos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Avaliação em Enfermagem/métodos , Avaliação em Enfermagem/estatística & dados numéricos , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Tempo , TriagemRESUMO
Adequate consumption of fruits and vegetables (FV) is a characteristic of a healthy diet but remains a challenge in nutrition interventions. This cross-sectional study explored the multi-directional relationships between maternal feeding self-efficacy, parenting confidence, child feeding behaviour, exposure to new food and FV intake in a cohort of 277 infants. Mothers with healthy infants weighing ≥2500 g and ≥37 weeks gestation were recruited post-natally from 11 South Australian hospitals. Socio-demographic data were collected at recruitment. At 6 months postnatal, infants were weighed and measured, and mothers completed a questionnaire exploring their perceptions of child feeding behaviour and child exposure to new foods. The questionnaire also included the Short Temperament Scale for Infants, Kessler 10 to measure maternal psychological distress and 5 items measuring maternal feeding self-efficacy. The number of occasions and variety of FV (number of subgroups within food groups) consumed by infants were estimated from a 24-hour dietary recall and 2 days food record. Structural equation modelling was performed using Mplus version 6.11. Median (IQR) variety scores were 2 (1-3) for fruit and 3 (2-5) for vegetable intake. The most popular FV consumed were apple (n = 108, 45.0%) and pumpkin (n = 143, 56.3%). None of the variables studied predicted the variety of child fruit intake. Parenting confidence, exposure to new foods and child feeding behaviour were indirectly related to child vegetable intake through maternal feeding self-efficacy while total number of children negatively predicted child vegetable variety (p < 0.05). This highlights the need for addressing antecedents of maternal feeding self-efficacy and the family eating environment as key strategies towards development of healthy eating in children.
Assuntos
Comportamento Alimentar , Frutas , Fenômenos Fisiológicos da Nutrição Materna , Autoeficácia , Verduras , Adulto , Austrália , Comportamento Infantil/psicologia , Pré-Escolar , Comportamento de Escolha , Estudos de Coortes , Estudos Transversais , Dieta , Feminino , Preferências Alimentares/psicologia , Humanos , Lactente , Fenômenos Fisiológicos da Nutrição do Lactente , Mães/psicologia , Poder Familiar/psicologia , Gravidez , Inquéritos e QuestionáriosRESUMO
Azoxymethane (AOM) is an alkylating agent that generates mutagenic and carcinogenic O(6)-methylguanine (O(6)meG) adducts in DNA. O(6)meG has been detected in human colonic DNA; hence, understanding the innate cellular events occurring in response to the formation of O(6)meG is important in developing preventive strategies for colorectal cancer. We explored the time-course, dose-response, and kinetics of O(6)meG formation and its removal by the DNA repair protein, O(6)-methylguanine DNA methyltransferase (MGMT), and apoptosis. In rats given AOM (10 mg/kg), the formation of O(6)meG occurs within 2 h of exposure, accompanied by rapid depletion of MGMT activity and followed by the induction of an acute apoptotic response that peaks at 6-8 h. MGMT repair and apoptosis are dependent on AOM dose and O(6)meG load. Apoptosis is initiated only when a high O(6)meG load is present and MGMT activity is fully depleted. AOM, 10 mg/kg, overwhelms MGMT repair for about 96 h and renewed MGMT activity is only observed once O(6)meG is no longer detectable. A threshold for apoptosis is observed at 6 h after 6 mg/kg AOM, when a high O(6)meG persists and MGMT activity is very low. These data suggest that apoptosis is probably triggered by O(6)meG, but only once the capacity of MGMT to repair O(6)meG is exhausted. In the colonic epithelium, apoptosis may be complementary to MGMT, in terms of minimising potentially mutagenic events and maintaining a healthy genome.
Assuntos
Apoptose/efeitos dos fármacos , Azoximetano/toxicidade , Colo/efeitos dos fármacos , Guanina/análogos & derivados , O(6)-Metilguanina-DNA Metiltransferase/metabolismo , Animais , Colo/citologia , Colo/metabolismo , Guanina/metabolismo , RatosRESUMO
Fish species data from a complex of seamounts off New Zealand termed the "Graveyard Seamount Complex' were analysed to investigate whether fish species composition varied between seamounts. Five seamount features were included in the study, with summit depths ranging from 748-891 m and elevation from 189-352 m. Measures of fish species dominance, rarity, richness, diversity, and similarity were examined. A number of factors were explored to explain variation in species composition, including latitude, water temperature, summit depth, depth at base, elevation, area, slope, and fishing effort. Depth at base and slope relationships were significant with shallow seamounts having high total species richness, and seamounts with a more gradual slope had high mean species richness. Species similarity was modelled and showed that the explanatory variables were driven primarily by summit depth, as well as by the intensity of fishing effort and elevation. The study showed that fish assemblages on seamounts can vary over very small spatial scales, in the order of several km. However, patterns of species similarity and abundance were inconsistent across the seamounts examined, and these results add to a growing literature suggesting that faunal communities on seamounts may be populated from a broad regional species pool, yet show considerable variation on individual seamounts.