Objective. To identify classification criteria for the rheumatic diseases and to evaluate their measurement properties and methodologic rigor using current measurement standards. Methods. We performed a systematic review of published literature and evaluated criteria sets for stated purpose, derivation and validation sample characteristics, methods of criteria generation and reduction, and consideration of validity, and reliability. Results. We identified 47 classification criteria sets encompassing 13 conditions. Approximately 50% of the criteria sets were developed based on expert opinion rather than patient data. Of the 47 criteria sets, control samples were derived from patients with rheumatic disease in 15 (32%) sets, from patients with nonrheumatic diseases in 4 (9%) sets, and from healthy participants in 2 (4%) sets. Where patient data were used, the number of cases ranged from 20 -588 and the number of controls from 50 -787. In only 1 (2%) criteria set was there a distinct separation between investigators who derived the criteria set and clinicians who provided cases and controls. Authors commented on the need for individual criterion to be reliable in 5 (11%) sets, precise in 5 (11%) sets; authors noted the importance of content validity in 12 (26%) sets, and construct validity in 12 (26%) sets. Conclusion. The variation in methodologic rigor used in sample selection affects the validity and reliability of the criteria sets in different clinical and research settings. Despite potential deficiencies in the methods used for some criteria development, the sensitivity and specificity of many criteria sets is moderate to strong. KEY WORDS. Classification criteria; Methodologic properties; Rheumatic disease. INTRODUCTIONClassification criteria for the rheumatic diseases are the basis for much research in clinical rheumatology. Classification criteria serve to define disease groups for clinical and epidemiologic studies. If they are not valid, participants without disease may be included in disease groups in studies, and participants with clear-cut disease may be excluded. Thus, the validity of classification criteria is Standards for the development and validation of classification criteria have changed substantially over time. Recommendations for the development and validation of criteria sets have been proposed based on the current standards of measurement science (1,2). The classification criteria currently in use have been published over several decades, and many of them precede our current understanding of how to develop valid criteria; therefore there is likely to be variation in the methodologies used in the development, validation, and performance characteristics of classification criteria. Furthermore, advances in our understanding of the pathophysiology of disease, diagnostic tests, patient populations, and treatments during the past 20 years suggest that some criteria sets need to be updated. Therefore, the methodology of the development and the subsequent validity and reliability of classification...

A B S T R AC TBackground. Serum metabolites are associated cross-sectionally with kidney function in population-based studies.

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SummaryHereditary atypical hemolytic uremic syndrome (aHUS), a dramatic disease frequently leading to dialysis, is associated with germline mutations of the CFH, CD46, or CFI genes. After identification of the mutation in an affected aHUS patient, single-site gene testing of relatives is the preventive care perspective. However, clinical data for family counselling are scarce.From the German-Speaking-Countries-aHUS-Registry, 33 index patients with mutations were approached for permission to offer relatives screening for their family-specific mutations and to obtain demographic and clinical data. Mutation screening was performed using direct sequencing. Age-adjusted penetrance of aHUS was calculated for each gene in index cases and in mutation-positive relatives.Sixty-one relatives comprising 41 parents and 20 other relatives were enrolled and mutations detected in 31/61. In total, 40 research participants had germline mutations in CFH, 19 in CD46 and in 6 CFI. Penetrance at age 40 was markedly reduced in mutation-positive relatives compared to index patients overall with 10% versus 67% (P < 0.001); 6% vs. 67% (P < 0.001) in CFH mutation carriers and 21% vs. 70% (P = 0.003) in CD46 mutation carriers.Age-adjusted penetrance for hereditary aHUS is important to understand the disease, and if replicated in the future, for genetic counselling.

The collection of the biomaterials was feasible without major problems at all participating study sites. However, the processing times were in some cases too long. To avoid pre-analytical artefacts in sample collection, appropriate standardisation among the study sites is necessary. To achieve this, blood and urine collection will have to be adapted to specific conditions of usage of liquid handling robots, which will be available at all participating study centres in the main study of the GNC. Strict compliance with the SOPs, thorough training of the staff and accurate documentation are mandatory to obtain high sample quality for later analyses. The so obtained biomaterials represent a valuable resource for research on infectious and other common complex diseases in the GNC.