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Updated: Jun 19, 2026

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
Published on: January 16, 2019
Cascade effects of laboratory testing are found to be rare in low disease probability situations: prospective cohort
Paul H H Houben1, Trudy van der Weijden, Ron A G Winkens
1Department of General Practice, School of Public Health and Primary Care (CAPHRI), Maastricht University, NL-6200 MD Maastricht, The Netherlands. paul.houben@hag.unimaas.nl
Objectives:
(1) To investigate the frequency of cascades of further diagnostic investigations and referrals after abnormal laboratory results in situations of low disease probability; (2) to investigate pretest and posttest determinants; and (3) to describe the cascades that occur.
Study Design And Setting:
Prospective cohort study in primary care in The Netherlands. Numbers of investigations/referrals were recorded during 6 months of follow-up for 256 patients with normal and abnormal laboratory results. The influences of the reason for ordering tests, interpretation of results, and pretest/posttest disease probability were examined.
Results:
After receiving the laboratory results, the physicians ordered further investigations for 22 (17.3%) patients with abnormal results and for two (1.6%) patients with normal results (P<0.001). They referred 12 (9.4%) patients with abnormal results and eight (6.2%) patients with normal results (P=0.33). Six patients had two investigations and/or referrals, and one patient had three referrals. There were significantly more investigations/referrals for results interpreted as abnormal (P=0.004) and for cases with a high posttest disease probability (P=0.001).
Conclusion:
This study suggests that cascade processes after laboratory testing in situations of low disease probability are limited in magnitude and frequency. Improving interpretations may help improve the appropriateness of further investigations and referrals.
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