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1.
J Appl Lab Med ; 4(2): 170-179, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31639662

RESUMO

BACKGROUND: Studies have illustrated how a low or undetectable high-sensitivity cardiac troponin (hs-cTn) concentration at emergency department (ED) presentation can rule out myocardial infarction (MI). A problem with using an undetectable hs-cTn cutoff is that this value may be defined differently among hospitals and is also difficult to monitor. In the present study, we assess the diagnostic performance of a clinical chemistry score (CCS) vs hs-cTn alone in the presentation blood sample in the ED for patient hospital admission in a multicenter setting. METHODS: From January 1 to June 30, 2018, consecutive patients with random glucose, creatinine (for an estimated glomerular filtration rate calculation), and hs-cTnI (Abbott, 2 hospitals, Hamilton, Ontario, n = 10496) or hs-cTnT (Roche, 4 hospitals, Calgary, Alberta, n = 25177) were assessed for hospital admission with the CCS (range of scores, 0-5) or hs-cTn alone. Sensitivity, specificity, predicative values, and likelihood ratios were calculated for a CCS of 0 and 5 and for hs-cTn alone (hs-cTnI cutoffs, 5 and 26 ng/L; hs-cTnT cutoffs, 6 and 14 ng/L). RESULTS: The CCS of 0 (CCS <1) identified approximately 10% of all patients as low risk and had a sensitivity for hospital admission of nearly 98% as compared to <93% when hs-cTnT (<6 ng/L) or hs-cTnI (<5 ng/L) cutoffs alone were used. A CCS ≥5 had a specificity for hospital admission >95%, with approximately 14% of patients at high risk. CONCLUSIONS: An ED disposition (admit or send home) using the presentation blood sample could occur in nearly 25% of all patients by use of the CCS.

2.
Comput Biol Med ; 113: 103389, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31442861

RESUMO

BACKGROUND: Gene set analysis is a popular approach to examine the association between a predefined gene set and a phenotype. Few methods have been developed for a continuous phenotype. However, often not all the genes within a significant gene set contribute to its significance. There is no gene set reduction method developed for continuous phenotype. We developed a computationally efficient analytical tool, called linear combination test for gene set reduction (LCT-GSR) to identify core subsets of gene sets associated with a continuous phenotype. Identifying the core subset enhances our understanding of the biological mechanism and reduces costs of disease risk assessment, diagnosis and treatment. RESULTS: We evaluated the performance of our analytical tool by applying it to two real microarray studies. In the first application, we analyzed pathway expression measurements in newborns' blood to discover core genes contributing to the variation in birth weight. On average, we were able to reduce the number of genes in the 33 significant gene sets of embryonic stem cell signatures by 84.3% resulting in 229 unique genes. Using immunologic signatures, on average we reduced the number of genes in the 210 significant gene sets by 89% leading to 1603 unique genes. There were 180 unique core genes overlapping across the two databases. In the second application, we analyzed pathway expression measurements in a cohort of lethal prostate cancer patients from Swedish Watchful Waiting cohort to identify main genes associated with tumor volume. On average, we were able to reduce the number of genes in the 17 gene sets by 90% resulting in 47 unique genes. CONCLUSIONS: We conclude that LCT-GSR is a statistically sound analytical tool that can be used to extract core genes associated with a continuous phenotype. It can be applied to a wide range of studies in which dichotomizing the continuous phenotype is neither easy nor meaningful. Reduction to the most predictive genes is crucial in advancing our understanding of issues such as disease prevention, faster and more efficient diagnosis, intervention strategies and personalized medicine.

3.
Can J Cardiol ; 33(8): 1006-1012, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28669701

RESUMO

BACKGROUND: Symptoms of acute coronary syndrome account for a large proportion of emergency department (ED) visits and hospitalizations. High-sensitivity troponin can rapidly rule out or rule in acute myocardial infarction (AMI) within a short time of ED arrival. We sought to validate test characteristics and classification performance of 2-hour high-sensitivity troponin T (hsTnT) algorithms for the rapid diagnosis of AMI. METHODS: We included consecutive patients from 4 academic EDs with suspected cardiac chest pain who had hsTnT assays performed 2 hours apart (± 30 minutes) as part of routine care. The primary outcome was AMI at 7 days. Secondary outcomes included major adverse cardiac events (mortality, AMI, and revascularization). Test characteristics and classification performance for multiple 2-hour algorithms were quantified. RESULTS: Seven hundred twenty-two patients met inclusion criteria. Seven-day AMI incidence was 10.9% and major adverse cardiac event incidence was 13.7%. A 2-hour rule-out algorithm proposed by Reichlin and colleagues ruled out AMI in 59.4% of patients with 98.7% sensitivity and 99.8% negative predictive value (NPV). The 2-hour rule-out algorithm proposed by the United Kingdom National Institute for Health and Care Excellence ruled out AMI in 50.3% of patients with similar sensitivity and NPV. Other exploratory algorithms had similar sensitivity but marginally better classification performance. According to Reichlin et al., the 2-hour rule-in algorithm ruled in AMI in 16.5% of patients with 92.4% specificity and 58.5% positive predictive value. CONCLUSIONS: Two-hour hsTnT algorithms can rule out AMI with very high sensitivity and NPV. The algorithm developed by Reichlin et al. had superior classification performance. Reichlin and colleagues' 2-hour rule-in algorithm had poor positive predictive value and might not be suitable for early rule-in decision-making.


Assuntos
Algoritmos , Diagnóstico Precoce , Serviço Hospitalar de Emergência , Infarto do Miocárdio/diagnóstico , Troponina T/sangue , Idoso , Biomarcadores/sangue , Eletrocardiografia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de Tempo
4.
Acad Emerg Med ; 24(10): 1267-1277, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28544100

RESUMO

BACKGROUND: The objective of this study was to quantify the sensitivity of very low concentrations of high-sensitivity cardiac troponin T (hsTnT) at ED arrival for acute myocardial infarction (AMI) in a large cohort of chest pain patients evaluated in real-world clinical practice. METHODS: This retrospective study included consecutive ED patients with suspected cardiac chest pain evaluated in four urban EDs, excluding those with ST-elevation AMI, cardiac arrest or abnormal kidney function. The primary outcomes were AMI at 7, 30, and 90 days. Secondary outcomes included major adverse cardiac events (MACE; all-cause mortality, AMI, and revascularization) and the individual MACE components. Test characteristics were calculated for hsTnT values from 3 to 200 ng/L . RESULTS: A total of 7,130 patients met inclusion criteria. AMI incidences at 7, 30, and 90 days were 5.8, 6.0, and 6.2%. When the hsTnT assay was performed at ED arrival, the limit of blank of the assay (3 ng/L) ruled out 7-day AMI in 15.5% of patients with 100% sensitivity and negative predictive value (NPV). The limit of detection of the assay (5 ng/L) ruled out AMI in 33.6% of patients with 99.8% sensitivity and 99.95% NPV for 7-day AMI. The limit of quantification (the Food and Drug Administration [FDA]-approved cutoff for lower the reportable limit) of 6 ng/L ruled out AMI in 42.2% of patients with 99.8% sensitivity and 99.95% NPV. The sensitivities of the cutoffs of <3, <5, and <6 ng/L for 7-day MACE were 99.6, 97.4, and 96.6%, respectively. The NPVs of the cutoffs of <3, <5, and <6 ng/L for 7-day MACE were 99.8, 99.5, and 99.4%, respectively. A secondary analysis was performed in a subgroup of 3,549 higher-risk patients who underwent serial troponin testing. In this subgroup, a cutoff of 3 ng/L ruled out 7-day AMI in 9.6% of patients with 100% sensitivity and NPV, a cutoff of 5 ng/L ruled out 7-day AMI in 23.3% of patients with 99.7% sensitivity and 99.9% NPV, and a cutoff of 6 ng/L ruled out 7-day AMI in 29.8% of patients with 99.7 and 99.9% NPV. In the higher-risk subgroup, the sensitivities of cutoffs of <3, <5, and <6 ng/L for 7-day MACE were 99.8, 97.4, and 96.6%, respectively. In this higher-risk subgroup, the NPV of cutoffs of <3, <5, and <6 ng/L for 7-day MACE were 99.7, 98.5, and 98.4%, respectively. CONCLUSIONS: When used in real-world clinical practice conditions, hsTnT concentrations < 6 ng/L (below the lower reportable limit for an FDA-approved assay) at the time of ED arrival can rule out AMI with very high sensitivity and NPV. The sensitivity for MACE is unacceptably low, and thus a single-troponin rule-out strategy should only be used in the context of a structured risk evaluation.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Infarto do Miocárdio/diagnóstico , Troponina T/sangue , Doença Aguda , Idoso , Biomarcadores/sangue , Dor no Peito/etiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Sensibilidade e Especificidade , Fatores de Tempo , Estados Unidos , United States Food and Drug Administration
5.
J Am Heart Assoc ; 4(8): e001954, 2015 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-26251282

RESUMO

BACKGROUND: We aimed to determine whether sepsis is associated with neurocognitive outcomes 4.5 years after congenital heart disease surgery in early infancy. METHODS AND RESULTS: A secondary analysis from a prospective inception cohort included all children having congenital heart disease surgery done at ≤6 weeks of age with cardiopulmonary bypass at the Western Canadian referral center from 1996 to 2009. Follow-up at the referral center determined the primary outcomes at 4.5 years with full-scale, performance, and verbal intelligence quotients on the Wechsler Preschool and Primary Scale of Intelligence. Perioperative variables were collected prospectively, and confirmation of blood culture-positive sepsis was done retrospectively. Multiple linear regression models for neurocognitive outcomes and multiple Cox proportional hazards regression for mortality were determined. Sepsis occurred in 97 of 502 patients (19%) overall and in 76 of 396 survivors (19%) with 4.5-year follow-up. By 4.5 years, there were 91 (18%) deaths, and 396 of 411 survivors (96%) had follow-up completed. Extracorporeal membrane oxygenation was associated with worse scores on all neurocognitive outcomes on multivariable regression; the association between extracorporeal membrane oxygenation and full-scale intelligence quotient had a regression coefficient of -13.6 (95% CI -21.3 to -5.9; P=0.001). Sepsis perioperatively was associated with performance and verbal intelligence quotients, with a trend for full-scale intelligence quotient (P=0.058) on multivariable regression. The regression coefficient for sepsis was strongest for performance intelligence quotient (-5.31; 95% CI -9.84 to -0.78; P=0.022). Sepsis was not but extracorporeal membrane oxygenation was associated with mortality by 4.5 years. CONCLUSIONS: Perioperative sepsis and extracorporeal membrane oxygenation were associated with adverse neurocognitive outcomes on multivariable regression. Quality improvement to prevent sepsis has the potential to improve long-term neurocognitive outcomes in infants after surgery for congenital heart disease.


Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Desenvolvimento Infantil , Cardiopatias Congênitas/cirurgia , Sistema Nervoso/crescimento & desenvolvimento , Sepse/etiologia , Fatores Etários , Canadá , Procedimentos Cirúrgicos Cardíacos/mortalidade , Pré-Escolar , Oxigenação por Membrana Extracorpórea/efeitos adversos , Feminino , Cardiopatias Congênitas/mortalidade , Humanos , Lactente , Recém-Nascido , Inteligência , Testes de Inteligência , Modelos Lineares , Masculino , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Prospectivos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Sepse/diagnóstico , Sepse/mortalidade , Sepse/fisiopatologia
6.
Int J Environ Res Public Health ; 12(8): 9575-88, 2015 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-26287224

RESUMO

The risk assessment matrix is a widely accepted, semi-quantitative tool for assessing risks, and setting priorities in risk management. Although the method can be useful to promote discussion to distinguish high risks from low risks, a published critique described a problem when the frequency and severity of risks are negatively correlated. A theoretical analysis showed that risk predictions could be misleading. We evaluated a practical public health example because it provided experiential risk data that allowed us to assess the practical implications of the published concern that risk matrices would make predictions that are worse than random. We explored this predicted problem by constructing a risk assessment matrix using a public health risk scenario-Tainted blood transfusion infection risk-That provides negative correlation between harm frequency and severity. We estimated the risk from the experiential data and compared these estimates with those provided by the risk assessment matrix. Although we validated the theoretical concern, for these authentic experiential data, the practical scope of the problem was limited. The risk matrix has been widely used in risk assessment. This method should not be abandoned wholesale, but users must address the source of the problem, apply the risk matrix with a full understanding of this problem and use matrix predictions to inform, but not drive decision-making.


Assuntos
Medição de Risco/métodos , Transfusão de Sangue , Tomada de Decisões , Transmissão de Doença Infecciosa , Humanos , Saúde Pública , Gestão de Riscos
7.
Ann Thorac Surg ; 99(6): 2124-32, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25912744

RESUMO

BACKGROUND: The purpose of this study was to determine whether a clinical outcome score derived from early postoperative events is associated with Bayley-III scores at 18 to 24 months among infants undergoing cardiopulmonary bypass surgery. METHODS: Included were infants aged 6 weeks or less who underwent surgery between 2005 and 2009, all of whom were referred for neurodevelopmental evaluation at 18 to 24 months. We excluded children with chromosomal abnormalities. The prespecified clinical outcome score had a range of 0 to 7. Lower scores indicated a more rapid postoperative recovery. Patients requiring extracorporeal life support were assigned a score of 7. RESULTS: One hundred and ninety-nine subjects were included. Surgical procedures were arterial switch (72), Norwood (60), repair of total anomalous pulmonary venous connection (29), and other (38). Nine subjects had postoperative extracorporeal life support. Mean clinical outcome score in the Norwood group was 4.0 ± 1.4 versus the arterial switch group (2.6 ± 1.5, p < 0.001), total anomalous pulmonary venous connection group (2.8 ± 1.8, p < 0.01), and other group (4.0 ± 1.8, p = not significant). Among children who had a clinical outcome score of 4 or greater, there was a decrease in Bayley-III cognitive score of 5.7 (95% confidence interval: 1.5 to 9.9, p = 0.009), a decrease in language score of 10.0 (95% confidence interval: 4.9 to 15.1, p < 0.001), and a decrease in motor score of 9.7 (95% confidence interval: 4.8 to 14.5, p < 0.001). Time until lactate of 2.0 mmol/L or less and highest 24-hour inotrope score increased with increasing clinical outcome score (p < 0.0001). CONCLUSIONS: Clinical outcome scores of 4 or greater were associated with significantly lower Bayley-III scores at 18 to 24 months. This score may be valuable as an endpoint when evaluating novel potential therapies for this high-risk population.


Assuntos
Ponte Cardiopulmonar/efeitos adversos , Desenvolvimento Infantil , Deficiências do Desenvolvimento/epidemiologia , Cardiopatias Congênitas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Alberta/epidemiologia , Pré-Escolar , Deficiências do Desenvolvimento/etiologia , Feminino , Seguimentos , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Testes Neuropsicológicos , Complicações Pós-Operatórias/etiologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco
8.
Pediatr Cardiol ; 36(2): 350-7, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25208496

RESUMO

The objective of this study was to determine neurocognitive outcomes 4.5 years after surgery for TAPVC in infancy and predictors of these outcomes. A cohort having TAPVC repair at age ≤6 weeks between 1998 and 2007 were followed by the Complex Pediatric Therapies Follow-up Program at 4.5 years. Outcomes include mortality, full-scale intelligence quotient (FSIQ), verbal IQ (VIQ), performance IQ (PIQ), visual motor integration (VMI), and general adaptive composite of the Adaptive Behavior Assessment System (GAC). There were 51 infants with simple TAPVC [4 year mortality 4 (8%)], and 16 with complex TAPVC [4 year mortality 7 (44%)], hazard ratio (HR) 7.02 (95% CI 2.05-24.07, p = 0.002). Of the 47 survivors after simple TAPVC, FSIQ (SD) was 92 (17), VIQ 92 (17), PIQ 94 (15), VMI 92 (15), and GAC 92 (15). Independent predictors of neurocognitive outcome included father's socioeconomic status, mother's years of schooling, gender, post-operative base deficit, and deep hypothermic circulatory arrest (DHCA) time. Complex TAPVC was associated on univariate analysis only with PIQ [81.9 (10.2) vs. 93.6 (15.4); p = 0.012] and FSIQ [80.7 (10.1) vs. 92.0 (17.7); p = 0.017]. Original peoples accounted for 25/51 (49%) of simple and 3/16 (19%) of complex TAPVC. Original peoples race was associated with 4-year mortality [HR 6.85 (95% CI 2.15, 21.76, p = 0.001)]. Survivors of TAPVC repair in early infancy have encouraging neurocognitive outcomes. Few independent predictors of neurocognitive outcome were found, with post-operative acidosis and DHCA time being potentially modifiable. Original peoples account for an unexpected proportion of patients (42%) and have a higher mortality.


Assuntos
Cognição , Síndrome de Cimitarra/cirurgia , Criança , Desenvolvimento Infantil , Pré-Escolar , Feminino , Seguimentos , Humanos , Testes de Inteligência , Masculino , Testes Neuropsicológicos
9.
BMC Bioinformatics ; 14: 212, 2013 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-23815123

RESUMO

BACKGROUND: Gene set analysis (GSA) methods test the association of sets of genes with a phenotype in gene expression microarray studies. Many GSA methods have been proposed, especially methods for use with a binary phenotype. Equally, if not more importantly however, is the ability to test the enrichment of a gene signature or pathway against the continuous phenotypes which are routinely and commonly observed in, for example, clinicopathological measurements. It is not always easy or meaningful to dichotomize continuous phenotypes into two classes, and attempting to do this may lead to the inaccurate classification of samples, which would affect the downstream enrichment analysis. In the present study, we have build on recent efforts to incorporate correlation structure within gene sets and pathways into the GSA test statistic. To address the issue of continuous phenotypes directly without the need for artificial discrete classification and thus increase the power of the test while ensuring computational efficiency and rigor, new GSA methods that can incorporate a covariance matrix estimator for a continuous phenotype may present an effective approach. RESULTS: We have designed a new method by extending the GSA approach called Linear Combination Test (LCT) from a binary to a continuous phenotype. Simulation studies and a real microarray dataset were used to compare the proposed LCT for a continuous phenotype, a modification of LCT (referred to as LCT2), and two publicly available GSA methods for continuous phenotypes. CONCLUSIONS: We found that the LCT methods performed better than the other two GSA methods; however, this finding should be understood in the context of our specific simulation studies and the real microarray dataset that were used to compare the methods. Free R-codes to perform LCT for binary and continuous phenotypes are available at http://www.ualberta.ca/~yyasui/homepage.html. The R-code to perform LCT for a continuous phenotype is available as Additional file 1.


Assuntos
Perfilação da Expressão Gênica/métodos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Fenótipo , Humanos , Leptina/genética , Leptina/metabolismo
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