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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Systematic review and pooled estimates for the diagnostic accuracy of serological markers for intestinal ischemia

NJ Evennett, MS Petrov, A Mittal, and JA Windsor.

Review published: 2009.

Link to full article: [Journal publisher]

CRD summary

The review assessed the diagnostic accuracy of 18 serologic markers of intestinal ischaemia and concluded that their performance is suboptimal for routine clinical use. Despite some limitations in the review process and analysis, this conclusion accurately reflects the data presented and is likely to be reliable.

Authors' objectives

To estimate the diagnostic accuracy of serologic markers of intestinal ischaemia and to compare the accuracy of different markers.

Searching

MEDLINE and EMBASE were searched to 31st January 2008. Search terms, including methodological terms for diagnostic accuracy studies, were reported. Bibliographies of identified studies and review articles were screened for additional studies. Unpublished material was sought using ClinicalTrials.gov databases. No language restrictions were applied.

Study selection

Studies of serologic markers for diagnosis of intestinal ischaemia were included if they reported sensitivity and specificity or data to calculate these parameters (numbers of true positive, false negative, false positive and true negative test results). Included studies were required to diagnose intestinal ischaemia at the time of surgery and/or autopsy (reference standard). The index test could not form part of the reference standard.

Most included studies were of acute abdomen patients. Prevalence of intestinal ischaemia ranged from 9% to 71%. Included studies assessed 18 different serologic markers. Diagnostic thresholds varied. Markers assessed by more than one study were: D-lactate, intestinal fatty acid binding protein (i-FABP), glutathione S-transferase (GST), D-dimer, serum phosphate, creatine kinase fraction BB (CK-BB), amylase, white blood count, pH and base excess.

The titles and abstracts of all citations were screened independently by two reviewers.

Assessment of study quality

Methodological quality of included studies was assessed using a modified 12-item version of the QUADAS (Quality Assessment of Diagnostic Accuracy Studies) tool to assess: inclusion of a representative spectrum; description of selection criteria; use of an appropriate reference standard; acceptable delay between index and reference tests; avoidance of partial verification; avoidance of differential verification; adequate description of the index and reference standard; blinded interpretation of test results; absence of uninterpretable results; and description of withdrawals. An overall quality score (maximum 12) was calculated.

Quality assessment was performed by one reviewer and checked by a second.

Data extraction

For each included study and each serologic marker, absolute numbers of true positive, false positive, true negative and false negative results were extracted. Sensitivity, specificity and positive and negative likelihood ratios were reported for each data set.

Two reviewers independently extracted data.

Methods of synthesis

Where a marker was assessed by two or more studies, pooled estimates of sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio (DOR), and their corresponding 95% confidence intervals (CIs), were calculated using the DerSimonian and Laird random-effects model.

For markers assessed by three or more studies, a summary receiver operating characteristic (sROC) curve was constructed using the method of Moses et al.

Between-study heterogeneity was assessed using the Χ2 and I2 tests. Where data from three or more studies were combined, threshold analyses (Spearman rank correlation, r) was used to assess whether a threshold effect (relationship between diagnostic threshold and test performance) existed. Funnel plots were constructed to explore the possibility of publication bias.

Results of the review

Twenty studies (978 participants) were included in the review. Fourteen of 20 studies were prospective. Median QUADAS score was 10 (range 7 to 11).

D-lactate (four studies): The pooled estimate of sensitivity was 0.82 (95% CI 0.65 to 0.93) and the pooled estimate of specificity was 0.48 (95% CI 0.38 to 0.58). The pooled estimate of positive likelihood ratios was 3.04 (95% CI 0.73 to 12.59) and the pooled estimate of negative likelihood ratios was 0.35 (95% CI 0.18 to 0.70). There was significant between study heterogeneity for specificity and positive likelihood ratios.

i-FABP (three studies): The pooled estimate of sensitivity was 0.72 (95% CI 0.51 to 0.88) and the pooled estimate of specificity was 0.73 (95% CI 0.62 to 0.83). The pooled estimate of positive likelihood ratios was 2.44 (95% CI 0.41 to 14.58) and the pooled estimate of negative likelihood ratios was 0.51 (95% CI 0.29 to 0.91). There was significant between study heterogeneity for specificity and positive likelihood ratios.

GST (three studies): The pooled estimate of sensitivity was 0.68 (95% CI 0.54 to 0.80) and the pooled estimate of specificity was 0.85 (05% CI 0.76 to 0.92). The pooled estimate of positive likelihood ratios was 3.38 (95% CI 1.64 to 6.97) and the pooled estimate of negative likelihood ratios was 0.40 (95% CI 0.11 to 1.47). There was significant between study heterogeneity for sensitivity and negative likelihood ratios.

D-dimer (three studies): The pooled estimate of sensitivity was 0.89 (95% CI 0.77 to 0.96) and the pooled estimate of specificity was 0.40 (95% CI 0.33 to 0.47). The pooled estimate of positive likelihood ratios was 1.48 (95% CI 1.28 to 1.71) and the pooled estimate of negative likelihood ratios was 0.30 (95% CI 0.14 to 0.64). There was no significant between study heterogeneity for any measure.

Two studies were identified for each of the traditional laboratory markers of intestinal ischaemia (amylase, white blood count, pH, and base excess). The pooled sensitivity estimate for these markers ranged from 0.38 (95% CI 0.24 to 0.54) for pH to 0.80 (95% CI 0.66 to 0.91) for white blood count. Pooled specificity estimates ranged from 0.42 (95% CI 0.20 to 0.67) for base excess to 0.84 (95% CI 0.60 to 0.97) for pH.

Data for other markers were reported in the paper.

Data were insufficient to allow definitive comparison between traditional and novel markers of intestinal ischaemia.

Funnel plots showed no evidence of publication bias.

Authors' conclusions

The performance of the currently available serologic markers of intestinal ischaemia were suboptimal for routine clinical use. Novel markers such as D-lactate, GST and i-FABP may offer improved diagnostic accuracy, although data to prove this definitively were still lacking.

CRD commentary

The review addressed a clearly stated research question, which was defined by appropriate inclusion criteria. A number of sources were searched without language restrictions to identify relevant studies. Use of methodological search terms for diagnostic accuracy studies may have reduced the sensitivity of the searches. Measures to reduce error and/or bias were reported throughout the review process. Methodological quality of included studies was assessed. However, generation of summary quality scores, as reported, is not recommended for QUADAS and has been shown to be an unreliable approach to quality assessment. Given apparent between-study heterogeneity, generation of pooled estimates of test characteristics was not informative. Despite some limitations, the authors conclusions accurately reflected the data presented and are likely to be reliable.

Implications of the review for practice and research

Practice: The authors stated that performance of serologic markers was disappointing and not particularly helpful for early diagnosis of intestinal ischaemia in the individual patient.

Research: The authors stated that future research should focus on development of a new, sensitive and intestine-specific marker to permit early and accurate diagnosis of intestinal

ischaemia in a variety of clinical settings. Research to identify a combination of markers, or an ‘‘intestinal ischaemia panel,’’ that reflect different aspects of intestinal viability was also suggested.

Funding

Not stated.

Bibliographic details

Evennett NJ, Petrov MS, Mittal A, Windsor JA. Systematic review and pooled estimates for the diagnostic accuracy of serological markers for intestinal ischemia. World Journal of Surgery 2009; 33(7): 1374-1383. [PubMed: 19424744]

Indexing Status

Subject indexing assigned by NLM

MeSH

Amylases /blood; Biological Markers /blood; Early Diagnosis; Female; Glutathione Transferase /blood; Humans; Intestines /blood supply; Ischemia /blood /diagnosis; Lactic Acid /blood; Leukocyte Count; Male; Predictive Value of Tests; Prognosis; Sensitivity and Specificity; Serologic Tests /methods

AccessionNumber

12009107041

Database entry date

31/03/2010

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 19424744