The role of procalcitonin (PCT), a widely used sepsis biomarker, in critically ill patients with sepsis is undetermined.
To investigate the effect of a low PCT cut-off on antibiotic prescription and ...to describe the relationships between PCT plasma concentration and sepsis severity and mortality.
This was a multicenter (11 Australian intensive care units ICUs), prospective, single-blind, randomized controlled trial involving 400 patients with suspected bacterial infection/sepsis and expected to receive antibiotics and stay in ICU longer than 24 hours. The primary outcome was the cumulative number of antibiotics treatment days at Day 28.
PCT was measured daily while in the ICU. A PCT algorithm, including 0.1 ng/ml cut-off, determined antibiotic cessation. Published guidelines and antimicrobial stewardship were used in all patients. Primary analysis included 196 (PCT) versus 198 standard care patients. Ninety-three patients in each group had septic shock. The overall median (interquartile range) number of antibiotic treatment days were 9 (6-21) versus 11 (6-22), P = 0.58; in patients with positive pulmonary culture, 11 (7-27) versus 15 (8-27), P = 0.33; and in patients with septic shock, 9 (6-22) versus 11 (6-24), P = 0.64; with an overall 90-day all-cause mortality of 35 (18%) versus 31 (16%), P = 0.54 in the PCT versus standard care, respectively. Using logistic regression, adjusted for age, ventilation status, and positive culture, the decline rate in log(PCT) over the first 72 hours independently predicted hospital and 90-day mortality (odds ratio 95% confidence interval, 2.76 1.10-6.96, P = 0.03; 3.20 1.30-7.89, P = 0.01, respectively).
In critically ill adults with undifferentiated infections, a PCT algorithm including 0.1 ng/ml cut-off did not achieve 25% reduction in duration of antibiotic treatment. Clinical trial registered with http://www.anzctr.org.au (ACTRN12610000809033).
The incidence of acute kidney injury (AKI) is increasing globally and it is much more common than end-stage kidney disease. AKI is associated with high mortality and cost of hospitalisation. Studies ...of treatments to reduce this high mortality have used differing renal replacement therapy (RRT) modalities and have not shown improvement in the short term. The reported long-term outcomes of AKI are variable and the effect of differing RRT modalities upon them is not clear. We used the prolonged follow-up of a large clinical trial to prospectively examine the long-term outcomes and effect of RRT dosing in patients with AKI.
We extended the follow-up of participants in the Randomised Evaluation of Normal vs. Augmented Levels of RRT (RENAL) study from 90 days to 4 years after randomization. Primary and secondary outcomes were mortality and requirement for maintenance dialysis, respectively, assessed in 1,464 (97%) patients at a median of 43.9 months (interquartile range IQR 30.0-48.6 months) post randomization. A total of 468/743 (63%) and 444/721 (62%) patients died in the lower and higher intensity groups, respectively (risk ratio RR 1.04, 95% CI 0.96-1.12, p = 0.49). Amongst survivors to day 90, 21 of 411 (5.1%) and 23 of 399 (5.8%) in the respective groups were treated with maintenance dialysis (RR 1.12, 95% CI 0.63-2.00, p = 0.69). The prevalence of albuminuria among survivors was 40% and 44%, respectively (p = 0.48). Quality of life was not different between the two treatment groups. The generalizability of these findings to other populations with AKI requires further exploration.
Patients with AKI requiring RRT in intensive care have high long-term mortality but few require maintenance dialysis. Long-term survivors have a heavy burden of proteinuria. Increased intensity of RRT does not reduce mortality or subsequent treatment with dialysis.
www.ClinicalTrials.govNCT00221013.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Current practice in the delivery of caloric intake (DCI) in patients with severe acute kidney injury (AKI) receiving renal replacement therapy (RRT) is unknown. We aimed to describe calorie ...administration in patients enrolled in the Randomized Evaluation of Normal vs. Augmented Level of Replacement Therapy (RENAL) study and to assess the association between DCI and clinical outcomes.
We performed a secondary analysis in 1456 patients from the RENAL trial. We measured the dose and evolution of DCI during treatment and analyzed its association with major clinical outcomes using multivariable logistic regression, Cox proportional hazards models, and time adjusted models.
Overall, mean DCI during treatment in ICU was low at only 10.9 ± 9 Kcal/kg/day for non-survivors and 11 ± 9 Kcal/kg/day for survivors. Among patients with a lower DCI (below the median) 334 of 729 (45.8%) had died at 90-days after randomization compared with 316 of 727 (43.3%) patients with a higher DCI (above the median) (P = 0.34). On multivariable logistic regression analysis, mean DCI carried an odds ratio of 0.95 (95% confidence interval (CI): 0.91-1.00; P = 0.06) per 100 Kcal increase for 90-day mortality. DCI was not associated with significant differences in renal replacement (RRT) free days, mechanical ventilation free days, ICU free days and hospital free days. These findings remained essentially unaltered after time adjusted analysis and Cox proportional hazards modeling.
In the RENAL study, mean DCI was low. Within the limits of such low caloric intake, greater DCI was not associated with improved clinical outcomes.
ClinicalTrials.gov number, NCT00221013.
The role of procalcitonin (PCT), a widely used sepsis biomarker, in critically ill patients with sepsis is undetermined. To investigate the effect of a low PCT cut-off on antibiotic prescription and ...to describe the relationships between PCT plasma concentration and sepsis severity and mortality. This was a multicenter (11 Australian intensive care units ICUs), prospective, single-blind, randomized controlled trial involving 400 patients with suspected bacterial infection/sepsis and expected to receive antibiotics and stay in ICU longer than 24 hours. The primary outcome was the cumulative number of antibiotics treatment days at Day 28. PCT was measured daily while in the ICU. A PCT algorithm, including 0.1 ng/ml cut-off, determined antibiotic cessation. Published guidelines and antimicrobial stewardship were used in all patients. Primary analysis included 196 (PCT) versus 198 standard care patients. Ninety-three patients in each group had septic shock. The overall median (interquartile range) number of antibiotic treatment days were 9 (6-21) versus 11 (6-22), P=0.58; in patients with positive pulmonary culture, 11 (7-27) versus 15 (8-27), P=0.33; and in patients with septic shock, 9 (6-22) versus 11 (6-24), P=0.64; with an overall 90-day all-cause mortality of 35 (18%) versus 31 (16%), P=0.54 in the PCT versus standard care, respectively. Using logistic regression, adjusted for age, ventilation status, and positive culture, the decline rate in log(PCT) over the first 72 hours independently predicted hospital and 90-day mortality (odds ratio 95% confidence interval, 2.76 1.10-6.96, P=0.03; 3.20 1.30-7.89, P=0.01, respectively). In critically ill adults with undifferentiated infections, a PCT algorithm including 0.1 ng/ml cut-off did not achieve 25% reduction in duration of antibiotic treatment. Clinical trial registered with http://www.anzctr.org.au (ACTRN12610000809033).
Gene prioritization is the process of ranking a list of candidate genes such that the genes that are most likely involved in a biological process of interest receive the highest rankings. In a ...supervised learning approach to gene prioritization, candidate genes are ranked in terms of their degree of similarity to genes that have already been shown to be involved in the process of interest. Gene prioritization thus can be cast as a classification task, in which a training set of genes and data associated with those genes is used to train a classifier to assign rankings to unknown genes, based on their degree of similarity to the training genes. This thesis describes the use of kernel methods, and particularly a method known as multiple kernel learning, for combining information from multiple data sources for purposes of gene prioritization. Multiple kernel learning facilitates the incorporation of heterogeneous data types into the assessment of similarity among genes. In addition, the rows of the kernel matrix can be repurposed as feature vectors. We apply clustering methods to these vectors to partition the gene list into related groups. We then perform functional enrichment analysis on the gene clusters to identify biological functions that are significantly represented in each gene cluster. We thus are able to use a single data structure, namely a kernel matrix representing similarities among genes based on multiple information sources, as the basis for three common types of bioinformatics analysis: gene prioritization, gene clustering, and functional annotation analysis of gene lists. This research contributes to the exploration of methods for extracting useful biological insights from the continually expanding knowledge base of biological data.
We have developed a knowledge-based simulation of DNA metabolism that accurately predicts the actions of enzymes on DNA under a large number of environmental conditions. Previous simulations of ...enzyme systems rely predominantly on mathematical models. We use a frame-based representation to model enzymes, substrates and conditions. Interactions between these objects are expressed using production rules and an underlying truth maintenance system. The system performs rapid inference and can explain its reasoning. A graphical interface provides access to all elements of the simulation, including object representations and explanation graphs. Predicting enzyme action is the first step in the development of a large knowledge base to envision the metabolic pathways of DNA replication and repair.
Mutual information algorithms have been used for the identification of gene-gene interactions in gene expression data. These methods have been hindered by a high false-positive rate. We explored the ...use of free-text abstracts as an additional source of information for assessing the biological relevance of predicted gene interactions. Our results suggest that the performance of a mutual information algorithm on this task can be enhanced by using text mining methods to refine the initial set of predictions.
Responding to the absence of readily available models in Australia for thinking about Christian higher education, this thesis investigates what might constitute its foundational principles and ...distinctive character. The thesis considers the Western Christian tradition, the history of the university, and the contemporary experience of Christian higher education in the United States to identify models for thinking about Christian higher education. It is argued that a central issue to be addressed in developing a distinctively Christian approach to scholarship is the relationship of faith and reason, an issue to which the Christian tradition offers a range of approaches. The question of faith and reason has a wider cultural significance since, it is argued, Western culture is fundamentally constituted by the relationship of Jerusalem and Athens, in which the inherent tensions do not obscure an ultimate commitment to the unity of truth. In contemporary debates over Christian higher education, the concept of faith-learning integration is a central issue. Given the variety of definitions and models proposed, the thesis considers the approaches which have been adopted in the Christian tradition. The approaches of Philo and the Church Fathers to classical learning are considered, with extended attention given to the 'faith seeking understanding' model attributed to St Augustine. Drawing upon Neoplatonism, Augustine's theory of illumination explained why true knowledge was dependent upon divine revelation. Augustine's approach also held that 'all truth is God's truth', and justified the appropriation of classical learning as analogous to the Hebrews 'spoiling Egypt' at the time of the Exodus. The Augustinian approach offers significant insight into the role of the will and the affections in knowing, and justifies belief as a reliance upon authority. While Augustine's is not the only model that might validly be termed 'Christian', and is not without its problems, it is a model which still has much to offer to Christian higher education today. The Augustinian approach has a profound historical significance since it established the epistemological framework for western Christendom throughout the middle ages. In responding to the criticism that the term 'Christian university' is an oxymoron, the thesis also considers aspects of the history of the medieval and Reformation universities, seeking to establish the extent to which it is possible for the university to be regarded as a Christian institution. It is argued that the university did not arise out of the rediscovery of Aristotelian philosophy, and that it is indeed possible to regard the university as a Christian institution for much of its history. The possibility of a Christian university today is thus not inconsistent with the history and institutional character of the university. The contributions to thinking about faith and learning and Christian higher education of Thomas Aquinas, Martin Luther, John Calvin, and John Henry Newman are also discussed. One of the critical tasks of Christian higher education generally, and of a Christian university specifically, is the synthesis or integration of faith and learning, of which both Augustine and Thomas Aquinas were exemplars. It is argued however that, while the Thomistic approach can validly be termed 'Christian', it has been more successfully pursued in Catholic institutions than in their Protestant counterparts in which a central authority to regulate the boundaries of the domains of faith and reason is absent. A critical issue for Christian higher education today is that of secularising pressures, and thus the recent history of the secularisation of Christian higher education institutions in the United States is also considered. It is argued that the secularisation of these institutions was due particularly to the view of faith and learning which they had adopted. The study concludes that the 'worldview' approach advocated by Abraham Kuyper offers an approach to scholarship which is both resistant to secularisation, and consistent with the Christian tradition, particularly as expressed by Augustine and Calvin.
The goal of this study was to assess psychiatry residency training directors’ perceptions of the training needs of psychiatry residents about ethnic and gender issues and to examine training program ...characteristics associated with appraisals of greater adequacy of training in these areas. A questionnaire designed to assess perceptions of training needs in ethnicity and gender was developed and completed by 142 psychiatry residency training directors. The training directors’ ratings of their residents’ adequacy of training about ethnic issues in psychiatric practice was significantly related to the residents’ contact with patients of diverse ethnic backgrounds, having coursework addressing ethnic issues included in the residency program, and the percentage of residents of minority ethnic backgrounds included in the program. The training directors’ ratings of their residents’ adequacy of training about gender issues in psychiatric practice was significantly and positively related to having course-work addressing gender issues included in the residency program and was appraised more negatively by the younger residency directors than by the older ones. The residents in psychiatry who are appraised as having the most adequate training in ethnicity and gender issues of their patients are those who received residency course-work on these subjects and are in psychiatry training programs including substantial numbers of minority residents and ample opportunities to work with minority patients.
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