Development and performance of electronic acute kidney injury triggers to identify pediatric patients at risk for nephrotoxic medication-associated harm.

BACKGROUND: Nephrotoxic medication-associated acute kidney injury (NTMx-AKI) is a costly clinical phenomenon and more common than previously recognized. Prior efforts to use technology to identify AKI have focused on detection after renal injury has occurred. OBJECTIVES: Describe an approach and provide a technical framework for the creation of risk-stratifying AKI triggers and the development of an application to manage the AKI trigger data. Report the performance characteristics of those triggers and the refinement process and on the challenges of implementation. METHODS: Initial manual trigger screening guided design of an automated electronic trigger report. A web-based application was designed to alleviate inefficiency and serve as a user interface and central workspace for the project. Performance of the NTMx exposure trigger reports from September 2011 to September 2013 were evaluated using sensitivity (SN), specificity (SP), positive and negative predictive values (PPV, NPV). RESULTS: Automated reports were created to replace manual screening for NTMx-AKI. The initial performance of the NTMx exposure triggers for SN, SP, PPV, and NPV all were ≥0.78, and increased over the study, with all four measures reaching ≥0.95 consistently. A web-based application was implemented that simplifies data entry and couriering from the reports, expedites results viewing, and interfaces with an automated data visualization tool. Sociotechnical challenges were logged and reported. CONCLUSION: We have built a risk-stratifying system based on electronic triggers that detects patients at-risk for NTMx-AKI before injury occurs. The performance of the NTMx-exposed reports has neared 100% through iterative optimization. The complexity of the trigger logic and clinical workflows surrounding NTMx-AKI led to a challenging implementation, but one that has been successful from technical, clinical, and quality improvement standpoints. This report summarizes the construction of a trigger-based application, the performance of the triggers, and the challenges uncovered during the design, build, and implementation of the system.

Public health approach to detection of non-O157 Shiga toxin-producing Escherichia coli: summary of two outbreaks and laboratory procedures.

Routine laboratory testing may not detect non-O157 Shiga toxin-producing Escherichia coli (STEC) reliably. Active clinical, epidemiological, environmental health, and laboratory collaboration probably influence successful detection and study of non-O157 STEC infection. We summarized two outbreak investigations in which such coordinated efforts identified non-O157 STEC disease and led to effective control measures. Outbreak 1 involved illness associated with consuming unpasteurized apple cider from a local orchard. Public health personnel were notified by a local hospital; stool specimens from ill persons contained O111 STEC. Outbreak 2 involved bloody diarrhoea at a correctional facility. Public health personnel were notified by the facility infection control officer; O45 STEC was the implicated agent. These reports highlight the ability of non-O157 STEC to cause outbreaks and demonstrate that a coordinated effort by clinicians, infection-control practitioners, clinical diagnostic laboratorians, and public health personnel can lead to effective identification, investigation, and prevention of non-O157 STEC disease.

Multistate outbreak of Escherichia coli O157:H7 infections associated with a national fast-food chain, 2006: a study incorporating epidemiological and food source traceback results.

A multistate outbreak of Escherichia coli O157:H7 infections occurred in the USA in November-December 2006 in patrons of restaurant chain A. We identified 77 cases with chain A exposure in four states - Delaware, New Jersey, New York, and Pennsylvania. Fifty-one (66%) patients were hospitalized, and seven (9%) developed haemolytic uraemic syndrome; none died. In a matched analysis controlling for age in 31 cases and 55 controls, illness was associated with consumption of shredded iceberg lettuce [matched odds ratio (mOR) 8·0, 95% confidence interval (CI) 1·1-348·1] and shredded cheddar cheese (mOR 6·2, CI 1·7-33·7). Lettuce, an uncooked ingredient, was more commonly consumed (97% of patients) than cheddar cheese (84%) and a single source supplied all affected restaurants. A single source of cheese could not explain the regional distribution of outbreak cases. The outbreak highlights challenges in conducting rapid multistate investigations and the importance of incorporating epidemiological study results with other investigative findings.

The major surface glycoprotein expression sites of two special forms of rat Pneumocystis carinii differ in structure.

Pneumocystis carinii forma specialis carinii has a unique locus called the UCS, which controls surface antigen variation by acting as the expression site for a family of genes encoding isoforms of the major surface glycoprotein (MSG). Every MSG mRNA begins with 380 nucleotides copied from the UCS locus. This UCS leader sequence is necessary for initiation of translation and for protein processing. Given the UCS's importance in P. carinii f. sp. carinii, it was of interest to examine the UCS locus in the related P. carinii f. sp. ratti. The first 380 nucleotides of P. carinii f. sp. ratti MSG mRNAs were 59% identical to the P. carinii f. sp. carinii UCS. However, the DNA encoding the P. carinii f. sp. ratti UCS was not unique in the genome. Instead, only the first 97 nucleotides came from a unique locus and the remainder from >/=7 loci. These data suggest that the two organisms may use different mechanisms to generate surface variation.

A new family of Pneumocystis carinii genes related to those encoding the major surface glycoprotein.

A new family of Pneumocystis carinii genes (called MSR for MSG-related) that encodes peptides related to the major surface glycoprotein (MSG) is described. Members of the MSR sequence family are linked to MSG genes and are located near the ends of at least 13 chromosomes. Transcripts encoding different MSR isoforms were present in a single population of P. carinii f. sp. carinii, showing that multiple MSR genes were expressed. Two size classes of MSR mRNA, 2.4 and 3.5 kb, were detected. Both sizes of MSR mRNA lacked the upstream conserved sequence (UCS), which is found on the 5' end of MSG mRNAs because MSG genes must be linked to the UCS to be transcribed. The absence of the UCS from MSR mRNAs suggests that expression of MSR genes does not require linkage to the UCS locus.

Major surface glycoprotein genes from Pneumocystis carinii f. sp. ratti.

Pneumocystis carinii occurs in a variety of mammals, each of which harbors one or more genetically distinct "special forms" of the microbe. Laboratory rats can be infected by two special forms, P. carinii f. sp. ratti and P. carinii f. sp. carinii. P. carinii f. sp. carinii has a variable antigen, the major surface glycoprotein (MSG), the expression of which is controlled by genetic recombination. Recombination may involve the CRJE, a 23-bp DNA sequence element invariant among P. carinii f. sp. carinii MSG genes. To better understand the role of the CRJE in MSG gene expression and to explore the possible role of MSG in P. carinii infection in rats, P. carinii f. sp. ratti MSG genes were studied. These genes were found to be related to MSG genes of P. carinii f. sp. carinii, but less so than MSG genes from P. carinii f. sp. carinii are to each other. P. carinii f. sp. ratti MSG genes were present throughout the genome and were expressed as an abundant mRNA species slightly smaller than that found in P. carinii f. sp. carinii. P. carinii f. sp. ratti MSG transcripts included a CRJE-like sequence only 78% identical to the CRJE of P. carinii f. sp. carinii. Comparison of MSG proteins from the two rat special forms of P. carinii to those from human, ferret, and mouse P. carinii did not support the hypothesis that growth in the rat lung requires certain primary MSG peptide sequences.

Human enteric defensin genes: chromosomal map position and a model for possible evolutionary relationships.

Defensins, a family of antimicrobial peptides isolated from several mammalian species, have a proposed functional role in innate host defense. In humans, certain defensin genes are expressed in phagocytic cells of hematopoietic origin, while others are expressed in Paneth cells, epithelial cells of the small intestine. In this study, we determined the chromosomal localization of the human defensin (HD) genes expressed in Paneth cells, HD-5 and HD-6. Analysis of a panel of human/hamster hybrids localized both HD-5 and HD-6 to chromosome 8. Southern blot analysis of DNA from cell lines that contain either chromosome 8 deletions or duplications further localized these two genes to 8p21-pter. Fluorescence in situ hybridization analysis of metaphase chromosomes using an HD-5 probe further supported the regional map assignment. Previous studies had localized the hematopoietic genes to chromosome 8p23, and the current work is consistent with both the enteric and the myeloid defensin genes being located at the same cytogenetic region of chromosome 8. In addition, the evolutionary relationships of this gene family were addressed using dot matrix sequence analysis. From this analysis, a model for the possible evolutionary history of the human defensin genes is proposed. According to this model, an early duplication of a primordial defensin gene yielded the ancestral genes of present day HD-5 and HD-6. The model further suggests that a subsequent unequal meiotic crossover event had generated an additional gene, comprised of a hybrid of sequences from the two parental genes, and that this hybrid gene then served as the ancestor to present day hematopoietic defensin genes.