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1.  Accuracy of LightCycler® SeptiFast for the detection and identification of pathogens in the blood of patients with suspected sepsis: a systematic review protocol 
BMJ Open  2012;2(1):e000392.
Background
There is growing interest in the potential utility of molecular diagnostics in improving the detection of life-threatening infection (sepsis). LightCycler® SeptiFast is a multipathogen probe-based real-time PCR system targeting DNA sequences of bacteria and fungi present in blood samples within a few hours. We report here the protocol of the first systematic review of published clinical diagnostic accuracy studies of this technology when compared with blood culture in the setting of suspected sepsis.
Methods/design
Data sources: the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects (DARE), the Health Technology Assessment Database (HTA), the NHS Economic Evaluation Database (NHSEED), The Cochrane Library, MEDLINE, EMBASE, ISI Web of Science, BIOSIS Previews, MEDION and the Aggressive Research Intelligence Facility Database (ARIF). Study selection: diagnostic accuracy studies that compare the real-time PCR technology with standard culture results performed on a patient's blood sample during the management of sepsis. Data extraction: three reviewers, working independently, will determine the level of evidence, methodological quality and a standard data set relating to demographics and diagnostic accuracy metrics for each study. Statistical analysis/data synthesis: heterogeneity of studies will be investigated using a coupled forest plot of sensitivity and specificity and a scatter plot in Receiver Operator Characteristic (ROC) space. Bivariate model method will be used to estimate summary sensitivity and specificity. The authors will investigate reporting biases using funnel plots based on effective sample size and regression tests of asymmetry. Subgroup analyses are planned for adults, children and infection setting (hospital vs community) if sufficient data are uncovered.
Dissemination
Recommendations will be made to the Department of Health (as part of an open-access HTA report) as to whether the real-time PCR technology has sufficient clinical diagnostic accuracy potential to move forward to efficacy testing during the provision of routine clinical care.
Registration
PROSPERO—NIHR Prospective Register of Systematic Reviews (CRD42011001289).
Article summary
Article focus
To describe the plans of a systematic review aimed at determining the diagnostic accuracy of a new real-time PCR technology (LightCycler® SeptiFast), designed to detect bloodborne pathogens in the setting of life-threatening infection (sepsis).
To highlight the unmet need for accurate and rapid infection diagnostics in the setting of life-threatening infection (sepsis).
Key messages
The study will provide the first independent systematic review of clinical validity studies of multiplex real-time PCR technology aimed at detecting circulating pathogen DNA straight from blood in the setting of suspected life-threatening infections (sepsis).
Based on the results of this study, independent recommendations will be made to the UK's Department of Health to help determine whether the real-time PCR technology has sufficient clinical diagnostic accuracy to move forward to efficacy testing during the provision of routine clinical care.
Strengths and limitations
The systematic review is focused on a single Conformité Européenne (CE)-marked real-time PCR technology designed for use in the setting of life-threatening infection (sepsis)
The systematic review is non-commercial and has been planned systematically by a multidisciplinary team of experts, working on behalf of the key stakeholders within a nationalised healthcare system.
Current clinical infection diagnostic reference standards may not have high diagnostic accuracy in all clinical settings and with all infections
doi:10.1136/bmjopen-2011-000392
PMCID: PMC3278490  PMID: 22240646
2.  The clinical diagnostic accuracy of rapid detection of healthcare-associated bloodstream infection in intensive care using multipathogen real-time PCR technology 
BMJ Open  2011;1(1):e000181.
Background
There is growing interest in the potential utility of real-time PCR in diagnosing bloodstream infection by detecting pathogen DNA in blood samples within a few hours. SeptiFast is a multipathogen probe-based real-time PCR system targeting ribosomal DNA sequences of bacteria and fungi. It detects and identifies the commonest pathogens causing bloodstream infection and has European regulatory approval. The SeptiFast pathogen panel is suited to identifying healthcare-associated bloodstream infection acquired during complex healthcare, and the authors report here the protocol for the first detailed health-technology assessment of multiplex real-time PCR in this setting.
Methods/design
A Phase III multicentre double-blinded diagnostic study will determine the clinical validity of SeptiFast for the rapid detection of healthcare-associated bloodstream infection, against the current service standard of microbiological culture, in an adequately sized population of critically ill adult patients. Results from SeptiFast and standard microbiological culture procedures in each patient will be compared at study conclusion and the metrics of clinical diagnostic accuracy of SeptiFast determined in this population setting. In addition, this study aims to assess further the preliminary evidence that the detection of pathogen DNA in the bloodstream using SeptiFast may have value in identifying the presence of infection elsewhere in the body. Furthermore, differences in circulating immune-inflammatory markers in patient groups differentiated by the presence/absence of culturable pathogens and pathogen DNA will help elucidate further the patho-physiology of infection developing in the critically ill.
Ethics and dissemination
Ethical approval has been granted by the North West 6 Research Ethics Committee (09/H1003/109). Based on the results of this first non-commercial study, independent recommendations will be made to The Department of Health (open-access health technology assessment report) as to whether SeptiFast has sufficient clinical diagnostic accuracy to move forward to efficacy testing during the provision of routine clinical care.
Article summary
Article focus
To highlight the unmet need for accurate and rapid infection diagnostics in the setting of life-threatening infection.
To describe the systematic plans of a clinical diagnostic validity study of a new real-time PCR technology, designed to detect circulating pathogen DNA associated with bloodstream infection.
To describe the clinical standards for sepsis and healthcare-associated infection diagnosis and identify how these standards will be utilised to determine the clinical validity of the new real-time PCR test in critically ill patients.
Key messages
The study will provide the first independent, systematic, clinical validity study of real-time PCR technologies in the focused setting of suspected life-threatening healthcare-associated infections during the provision of routine emergency critical care.
Based on the results of this study, independent recommendations will be made to the UK's Department of Health as to whether the real-time PCR technology has sufficient clinical diagnostic accuracy to move forward to efficacy testing during the provision of routine clinical care.
Strengths and limitations of this study
The study is focused on a carefully delineated clinical cohort at significant risk of developing life-threatening infection.
The study is non-commercial and has been planned systematically by a multidisciplinary team of experts and patient representatives, working on behalf of the key stakeholders within a nationalised healthcare system.
Current clinical infection diagnosis standards may not have a high diagnostic accuracy in all settings and with all infections.
There is a documented high rate of broad-spectrum antimicrobial therapies delivered to critically ill patients empirically which could confound the comparison between culture methods and pathogen DNA-detection methods.
doi:10.1136/bmjopen-2011-000181
PMCID: PMC3191580  PMID: 22021785
Intensive &critical care; adult intensive & critical care; molecular diagnostics; adult intensive & critical care; adult thoracic medicine; adult surgery; Colorectal surgery; inflammatory bowel disease; Nutritional support; wound management

Results 1-2 (2)