Characteristics and Outcomes of Patients Discharged Home from an Emergency Department with Acute Kidney Injury: A Population-Based Cohort Study

We designed a population-based cohort study to describe the characteristics and outcomes of 6346 adults discharged home from an emergency department (ED) with acute kidney injury (AKI). Within 30 days of discharge, 149 (2.3%) patients died (stage 1: 2.1%, stage 2: 5.2%, and stage 3 AKI: 15.9%). We also compared 30-day mortality to patients hospitalized with AKI and patients discharged home with no AKI in two separate propensity score-matched analyses. An ED discharge versus hospitalization was associated with lower 30-day mortality (3.0% vs. 11.9%, relative risk (RR): 0.25, 95% confidence interval (CI): 0.21-0.30). An ED discharge home with AKI versus no AKI was associated with higher 30-day mortality (2.2% vs. 1.4%, RR: 1.56, 95% CI: 1.20-2.04). Although sicker patients are appropriately hospitalized, patients discharged home from the ED with AKI remain at risk of adverse outcomes. A better understanding of care appears warranted, as is testing strategies to improve care

A new approach for the analysis of bacterial microarray-based Comparative Genomic Hybridization: insights from an empirical study

BACKGROUND: Microarray-based Comparative Genomic Hybridization (M-CGH) has been used to characterize the extensive intraspecies genetic diversity found in bacteria at the whole-genome level. Although conventional microarray analytical procedures have proved adequate in handling M-CGH data, data interpretation using these methods is based on a continuous character model in which gene divergence and gene absence form a spectrum of decreasing gene conservation levels. However, whereas gene divergence may yet be accompanied by retention in gene function, gene absence invariably leads to loss of function. This distinction, if ignored, leads to a loss in the information to be gained from M-CGH data. We present here results from experiments in which two genome-sequenced strains of C. jejuni were compared against each other using M-CGH. Because the gene content of both strains was known a priori, we were able to closely examine the effects of sequence divergence and gene absence on M-CGH data in order to define analytical parameters for M-CGH data interpretation. This would facilitate the examination of the relative effects of sequence divergence or gene absence in comparative genomics analyses of multiple strains of any species for which genome sequence data and a DNA microarray are available. RESULTS: As a first step towards improving the analysis of M-CGH data, we estimated the degree of experimental error in a series of experiments in which identical samples were compared against each other by M-CGH. This variance estimate was used to validate a Log Ratio-based methodology for identification of outliers in M-CGH data. We compared two genome strains by M-CGH to examine the effect of probe/target identity on the Log Ratios of signal intensities using prior knowledge of gene divergence and gene absence to establish Log Ratio thresholds for the identification of absent and conserved genes. CONCLUSION: The results from this empirical study validate the Log Ratio thresholds that have been used in other studies to establish gene divergence/absence. Moreover, the analytical framework presented here enhances the information content derived from M-CGH data by shifting the focus from divergent/absent gene detection to accurate detection of conserved and absent genes. This approach closely aligns the technical limitations of M-CGH analysis with practical limitations on the biological interpretation of comparative genomics data

Aspirin and clonidine in non-cardiac surgery: acute kidney injury substudy protocol of the Perioperative Ischaemic Evaluation (POISE) 2 randomised controlled trial

IntroductionPerioperative Ischaemic Evaluation-2 (POISE-2) is an international 2×2 factorial randomised controlled trial of low-dose aspirin versus placebo and low-dose clonidine versus placebo in patients who undergo non-cardiac surgery. Perioperative aspirin (and possibly clonidine) may reduce the risk of postoperative acute kidney injury (AKI).Methods and analysisAfter receipt of grant funding, serial postoperative serum creatinine measurements began to be recorded in consecutive patients enrolled at substudy participating centres. With respect to the study schedule, the last of over 6500 substudy patients from 82 centres in 21 countries were randomised in December 2013. The authors will use logistic regression to estimate the adjusted OR of AKI following surgery (compared with the preoperative serum creatinine value, a postoperative increase ≥26.5 μmol/L in the 2 days following surgery or an increase of ≥50% in the 7 days following surgery) comparing each intervention to placebo, and will report the adjusted relative risk reduction. Alternate definitions of AKI will also be considered, as will the outcome of AKI in subgroups defined by the presence of preoperative chronic kidney disease and preoperative chronic aspirin use. At the time of randomisation, a subpopulation agreed to a single measurement of serum creatinine between 3 and 12 months after surgery, and the authors will examine intervention effects on this outcome.Ethics and disseminationThe authors were competitively awarded a grant from the Canadian Institutes of Health Research for this POISE-2 AKI substudy. Ethics approval was obtained for additional kidney data collection in consecutive patients enrolled at participating centres, which first began for patients enrolled after January 2011. In patients who provided consent, the remaining longer term serum creatinine data will be collected throughout 2014. The results of this study will be reported no later than 2015.Clinical Trial Registration NumberNCT01082874

A new approach for the analysis of bacterial microaray-based Comparative Genomic Hybridization : Insights from an empirical study

NRC publication: Ye

Comparative genomic analysis of <it>Campylobacter jejuni </it>associated with Guillain-Barré and Miller Fisher syndromes: neuropathogenic and enteritis-associated isolates can share high levels of genomic similarity

<p>Abstract</p> <p>Background</p> <p><it>Campylobacter jejuni </it>infection represents the most frequent antecedent infection triggering the onset of the neuropathic disorders Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS). Although sialylated ganglioside-mimicking lipo-oligosaccharide (LOS) structures are the strongest neuropathogenic determinants in <it>C. jejuni</it>, they do not appear to be the only requirement for a neuropathic outcome since strains capable of their production have been isolated from patients with uncomplicated cases of enteritis. Consequently, other pathogen and/or host-related factors contribute to the onset of neurological complications. We have used comparative genomic hybridization to perform a detailed genomic comparison of strains isolated from GBS/MFS and enteritis-only patients. Our dataset, in which the gene conservation profile for 1712 genes was assayed in 102 strains, including 56 neuropathogenic isolates, represents the largest systematic search for <it>C. jejuni </it>factors associated with GBS/MFS to date and has allowed us to analyze the genetic background of neuropathogenic <it>C. jejuni </it>strains with an unprecedented level of resolution.</p> <p>Results</p> <p>The majority of GBS/MFS strains can be assigned to one of six major lineages, suggesting that several genetic backgrounds can result in a neuropathogenic phenotype. A statistical analysis of gene conservation rates revealed that although genes involved in the sialylation of LOS structures were significantly associated with neuropathogenic strains, still many enteritis-control strains both bear these genes and share remarkable levels of genomic similarity with their neuropathogenic counterparts. Two capsule biosynthesis genes (Cj1421c and Cj1428c) showed higher conservation rates among neuropathogenic strains compared to enteritis-control strains. Any potential involvement of these genes in neuropathogenesis must be assessed. A single gene (HS:3 Cj1135) had a higher conservation rate among enteritis-control strains. This gene encodes a glucosyltransferase that is found in some of the LOS classes that do not express ganglioside mimics.</p> <p>Conclusion</p> <p>Our findings corroborate that neuropathogenic factors may be transferred between unrelated strains of different genetic background. Our results would also suggest that the failure of some strains isolated from uncomplicated cases of enteritis to elicit a neuropathic clinical outcome may be due to subtle genetic differences that silence their neuropathogenic potential and/or due to host-related factors.</p> <p>The microarray data has been deposited in NCBI's Gene Expression Omnibus under accession number GSE3579.</p

Large-Scale Comparative Genomics Meta-Analysis of Campylobacter jejuni Isolates Reveals Low Level of Genome Plasticity

We have used comparative genomic hybridization (CGH) on a full-genome Campylobacter jejuni microarray to examine genome-wide gene conservation patterns among 51 strains isolated from food and clinical sources. These data have been integrated with data from three previous C. jejuni CGH studies to perform a meta-analysis that included 97 strains from the four separate data sets. Although many genes were found to be divergent across multiple strains (n = 350), many genes (n = 249) were uniquely variable in single strains. Thus, the strains in each data set comprise strains with a unique genetic diversity not found in the strains in the other data sets. Despite the large increase in the collective number of variable C. jejuni genes (n = 599) found in the meta-analysis data set, nearly half of these (n = 276) mapped to previously defined variable loci, and it therefore appears that large regions of the C. jejuni genome are genetically stable. A detailed analysis of the microarray data revealed that divergent genes could be differentiated on the basis of the amplitudes of their differential microarray signals. Of 599 variable genes, 122 could be classified as highly divergent on the basis of CGH data. Nearly all highly divergent genes (117 of 122) had divergent neighbors and showed high levels of intraspecies variability. The approach outlined here has enabled us to distinguish global trends of gene conservation in C. jejuni and has enabled us to define this group of genes as a robust set of variable markers that can become the cornerstone of a new generation of genotyping methods that use genome-wide C. jejuni gene variability data

Ambulatory care after acute kidney injury: an opportunity to improve patient outcomes

Abstract Purpose of review Acute kidney injury (AKI) is an increasingly common problem among hospitalized patients. Patients who survive an AKI-associated hospitalization are at higher risk of de novo and worsening chronic kidney disease, end-stage kidney disease, cardiovascular disease, and death. For hospitalized patients with dialysis-requiring AKI, outpatient follow-up with a nephrologist within 90 days of hospital discharge has been associated with enhanced survival. However, most patients who survive an AKI episode do not receive any follow-up nephrology care. This narrative review describes the experience of two new clinical programs to care for AKI patients after hospital discharge: the Acute Kidney Injury Follow-up Clinic for adults (St. Michael’s Hospital and University Health Network, Toronto, Canada) and the AKI Survivor Clinic for children (Cincinnati Children’s Hospital, USA). Sources of information MEDLINE, PubMed, ISI Web of Science Findings These two ambulatory clinics have been in existence for close to two (adult) and four (pediatric) years, and were developed separately and independently in different populations and health systems. The components of both clinics are described, including the target population, referral process, medical interventions, patient education activities, and follow-up schedule. Common elements include targeting patients with KDIGO stage 2 or 3 AKI, regular audits of the inpatient nephrology census to track eligible patients, medication reconciliation, and education on the long-term consequences of AKI. Limitations Despite the theoretical benefits of post-AKI follow-up and the clinic components described, there is no high quality evidence to prove that the interventions implemented in these clinics will reduce morbidity or mortality. Therefore, we also present a plan to evaluate the adult AKI Follow-up Clinic in order to determine if it can improve clinical outcomes compared to patients with AKI who do not receive follow-up care. Implications Follow-up of AKI survivors is low, and this review describes two different clinics that care for patients who survive an AKI episode. We believe that sharing the experiences of the AKI Follow-up Clinic and AKI Survivor Clinic provide physicians with a feasible framework to implement their own clinics, which may help AKI patients receive outpatient care commensurate with their high risk status

Ambulatory Care after Acute Kidney Injury: An Opportunity to Improve Patient Outcomes

Purpose of review: Acute kidney injury (AKI) is an increasingly common problem among hospitalized patients. Patients who survive an AKI-associated hospitalization are at higher risk of de novo and worsening chronic kidney disease, end-stage kidney disease, cardiovascular disease, and death. For hospitalized patients with dialysis-requiring AKI, outpatient follow-up with a nephrologist within 90 days of hospital discharge has been associated with enhanced survival. However, most patients who survive an AKI episode do not receive any follow-up nephrology care. This narrative review describes the experience of two new clinical programs to care for AKI patients after hospital discharge: the Acute Kidney Injury Follow-up Clinic for adults (St. Michael's Hospital and University Health Network, Toronto, Canada) and the AKI Survivor Clinic for children (Cincinnati Children's Hospital, USA). Sources of information: MEDLINE, PubMed, ISI Web of Science Findings: These two ambulatory clinics have been in existence for close to two (adult) and four (pediatric) years, and were developed separately and independently in different populations and health systems. The components of both clinics are described, including the target population, referral process, medical interventions, patient education activities, and follow-up schedule. Common elements include targeting patients with KDIGO stage 2 or 3 AKI, regular audits of the inpatient nephrology census to track eligible patients, medication reconciliation, and education on the long-term consequences of AKI. Limitations: Despite the theoretical benefits of post-AKI follow-up and the clinic components described, there is no high quality evidence to prove that the interventions implemented in these clinics will reduce morbidity or mortality. Therefore, we also present a plan to evaluate the adult AKI Follow-up Clinic in order to determine if it can improve clinical outcomes compared to patients with AKI who do not receive follow-up care. Implications: Follow-up of AKI survivors is low, and this review describes two different clinics that care for patients who survive an AKI episode. We believe that sharing the experiences of the AKI Follow-up Clinic and AKI Survivor Clinic provide physicians with a feasible framework to implement their own clinics, which may help AKI patients receive outpatient care commensurate with their high risk status

Comparative genomic analysis of associated with Guillain-Barré and Miller Fisher syndromes: neuropathogenic and enteritis-associated isolates can share high levels of genomic similarity-4

<p><b>Copyright information:</b></p><p>Taken from "Comparative genomic analysis of associated with Guillain-Barré and Miller Fisher syndromes: neuropathogenic and enteritis-associated isolates can share high levels of genomic similarity"</p><p>http://www.biomedcentral.com/1471-2164/8/359</p><p>BMC Genomics 2007;8():359-359.</p><p>Published online 5 Oct 2007</p><p>PMCID:PMC2174954.</p><p></p> neuropathogenic strains. Both types of strains can show substantial similarities in genomic background, which includes similarities at several hypervariable regions. The lineage (LIN) of the 56 neuropathogenic strains is shown. Highly similar enteritis-control/neuropathogenic strain pairs (boxes a through d) are shown in expanded form in Figure 3. Legend: Hypervariable loci (L – LOS locus; F – flagellar modification locus; C – capsular locus; R/M – restriction-modification locus); Strain sets (DG: Dutch GBS; DM: Dutch MFS; DE: Dutch enteritis; JG: Japanese GBS; JM: Japanese MFS; JE: Japanese enteritis; CG: Curaçao GBS; CE: Curaçao enteritis)

Comparative genomic analysis of associated with Guillain-Barré and Miller Fisher syndromes: neuropathogenic and enteritis-associated isolates can share high levels of genomic similarity-0

<p><b>Copyright information:</b></p><p>Taken from "Comparative genomic analysis of associated with Guillain-Barré and Miller Fisher syndromes: neuropathogenic and enteritis-associated isolates can share high levels of genomic similarity"</p><p>http://www.biomedcentral.com/1471-2164/8/359</p><p>BMC Genomics 2007;8():359-359.</p><p>Published online 5 Oct 2007</p><p>PMCID:PMC2174954.</p><p></p>how unique gene conservation profiles and fail to cluster robustly with any major lineage. Branches with greater than 75% bootstrap support are shown in red. Although data is displayed including capsular genes (gray box), these genes were removed during cluster analysis to avoid biasing results. Highly divergent/Absent genes shown in red; Moderately Divergent genes are shown in blue. Legend: Hypervariable loci (L – LOS locus; F – flagellar modification locus; C – capsular locus; R/M – restriction-modification locus); Strain sets (DG: Dutch GBS; DM: Dutch MFS; JG: Japanese GBS; JM: Japanese MFS; CG: Curaçao GBS)