Clinical Chemistry - Ultimo numero

For medical tests that have a central role in clinical decision-making, current guidelines advocate outcome-based analytical performance specifications. Given that empirical (clinical trial-style) analyses are often impractical or unfeasible in this context, the ability to set such specifications is expected to rely on indirect studies to calculate the impact of test measurement uncertainty on downstream clinical, operational, and economic outcomes. Currently, however, a lack of awareness and guidance concerning available alternative indirect methods is limiting the production of outcome-based specifications. Therefore, our aim was to review available indirect methods and present an analytical framework to inform future outcome-based performance goals.

A methodology review consisting of database searches and extensive citation tracking was conducted to identify studies using indirect methods to incorporate or evaluate the impact of test measurement uncertainty on downstream outcomes (including clinical accuracy, clinical utility, and/or costs). Eighty-two studies were identified, most of which evaluated the impact of imprecision and/or bias on clinical accuracy. A common analytical framework underpinning the various methods was identified, consisting of 3 key steps: (a) calculation of "true" test values; (b) calculation of measured test values (incorporating uncertainty); and (c) calculation of the impact of discrepancies between (a) and (b) on specified outcomes. A summary of the methods adopted is provided, and key considerations are discussed.

Various approaches are available for conducting indirect assessments to inform outcome-based performance specifications. This study provides an overview of methods and key considerations to inform future studies and research in this area.

Gardnerella vaginalis is implicated as one of the causative agents of bacterial vaginosis, but it can also be isolated from the vagina of healthy women. Previous efforts to study G. vaginalis identified 4 to 6 clades, but average nucleotide identity analysis indicates that G. vaginalis may be multiple species. Recently, Gardnerella was determined to be 13 genomospecies, with Gardnerella piottii, Gardnerella leopoldii, and Gardnerella swidsinkii delineated as separate species.

We accessed 103 publicly available genomes annotated as G. vaginalis. We performed comprehensive taxonomic and phylogenomic analysis to quantify the number of species called G. vaginalis, the similarity of their core genes, and their burden of their accessory genes. We additionally analyzed publicly available metatranscriptomic data sets of bacterial vaginosis to determine whether the newly delineated genomospecies are present, and to identify putative conserved features of Gardnerella pathogenesis.

Gardnerella could be classified into 8 to 14 genomospecies depending on the in silico classification tools used. Consensus classification identified 9 different Gardnerella genomospecies, here annotated as GS01 through GS09. The genomospecies could be readily distinguished by the phylogeny of their shared genes and burden of accessory genes. All of the new genomospecies were identified in metatranscriptomes of bacterial vaginosis.

Multiple Gardnerella genomospecies operating in isolation or in concert with one another may be responsible for bacterial vaginosis. These results have important implications for future efforts to understand the evolution of the Gardnerella genomospecies, host–pathogen interactions of the genomospecies during bacterial vaginosis, diagnostic assay development for bacterial vaginosis, and metagenomic investigations of the vaginal microbiota.