Thrombotic microangiopathy (TMA) is a pattern of endothelial damage that can be found in association with diverse clinical conditions such as malignant hypertension. Although the pathophysiological mechanisms differ, accumulating evidence links complement dysregulation to various TMA syndromes and in particular the atypical hemolytic uremic syndrome. Here, we evaluated the role of complement in nine consecutive patients with biopsy-proven renal TMA attributed to severe hypertension. Profound hematologic symptoms of TMA were uncommon. In six out of nine patients, we found mutations C3 in three, CFI in one, CD46 in one, and/or CFH in two patients either with or without the risk CFH-H3 haplotype in four patients. Elevated levels of the soluble C5b-9 and renal deposits of C3c and C5b-9 along the vasculature and/or glomerular capillary wall, confirmed complement activation in vivo. In contrast to patients without genetic defects, patients with complement defects invariably progressed to end-stage renal disease, and disease recurrence after kidney transplantation seems common. Thus, a subset of patients with hypertension-associated TMA falls within the spectrum of complement-mediated TMA, the prognosis of which is poor. Hence, testing for genetic complement abnormalities is warranted in patients with severe hypertension and TMA on renal biopsy to adopt suitable treatment options and prophylactic measures.

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Assessment of impairment and function is essential in order to monitor joint status and evaluate therapeutic interventions in patients with haemophilia. The improvements in the treatment of haemophilia have required the development of more sensitive tools to detect the more minor dysfunctions that may now be apparent. This paper outlines some of the recent developments in this field. The Haemophilia Joint Health Score (HJHS) provides a systematic and robust measure of joint impairment. The MRI Scoring System has been designed to provide a comprehensive scoring system combining both progressive and additive scales. The Functional Independence Score for Haemophilia (FISH) has been developed to assess performance of functional activities and can be used in conjunction with the Haemophilia Activities List (HAL) which provides a self report measure of function. It is recommended that both measures are evaluated as these tools measure different constructs. Further refinement and testing of the psychometric properties of all of these tools is in progress. More widespread use of these tools will enable the sharing of data across the world so promoting best practice and ultimately enhancing patient care.

BackgroundThe original version of the Childhood Health Assessment Questionnaire (CHAQ30orig) suffers from a ceiling effect and hence has reduced clinical validity. The purpose of this study was to evaluate the effect of adding eight more demanding items (CHAQ38) and a new categorical response option (CATII) on discriminant validity and score distribution in a European patient sample.MethodsEighty-nine children with Juvenile Idiopathic arthritis (JIA) and 22 healthy controls, aged 7-16 years, were recruited from eight centres across Europe. Eight new CHAQ items and scoring option were translated back and forth for the countries in which they were not already present. Demographic, clinical, and CHAQ data were collected on-site. Subsequently, five different scoring methods were applied, i.e. the original method (CHAQ30orig) and four alternatives. These alternatives consisted of the mean item scores for the 30 and 38-question versions with either the original (CATI), or the new categorical response option (CATII). The five versions were tested for their ability to distinguish between patients and controls. Furthermore score distributions were evaluated and visualized by box and whisker plots.ResultsTwo CHAQ revisions with the new response option showed poor discriminative ability, whereas one revised version (CHAQ38CATI) had comparable discriminative ability comparable to the original CHAQ. A profound ceiling effect was observed in the original scoring method of the CHAQ (27%). The addition of eight more demanding items and application of a plain mean item score reduced this significantly to 14% (χ2 = 4.21; p < 0.05).ConclusionsRevising the CHAQ by adding eight more demanding items and applying a plain mean item scoring (CHAQ38CATI) maintained discriminant ability and reduced the ceiling effect in a European patient sample. The new categorical response option (CATII) seemed promising, but was less able to distinguish children with JIA from healthy controls and had less favourable distribution characteristics. The CHAQ38CATI is advocated for future use in mildly affected JIA patients.