Development and validation of the Physician's Global Assessment of Fingernail Psoriasis.

BACKGROUND: Several clinician-rated scoring systems are available to assess nail psoriasis severity, but only one has been partially validated. OBJECTIVE: To develop and validate the Physician's Global Assessment of Fingernail Psoriasis (PGA-F), a new clinician-rated severity scale. METHODS: A literature review, concept elicitation, pilot cognitive debriefing and clinical expert consultations informed the development of the PGA-F. A multistage mixed-methods analysis consisted of practising dermatologist cognitive interviews (n = 10) for instrument clarity, relevance and comprehensiveness. Inter-rater reliability (IRR) of ratings from dermatologists (n = 22) and clinical trial investigators (n = 8) was tested using many-facet Rasch analysis. Concurrent validity between the PGA-F and modified Nail Psoriasis Severity Index (mNAPSI) at screening and baseline was assessed along with the degree of discrimination. Intraclass correlation coefficient (ICC) for single raters at multiple assessments determined IRR. RESULTS: The PGA-F synthesizes severity ratings across multiple disease features that classify individuals into 1 of 5 levels (clear to severe). Cognitive interviews confirmed content validity: all (n = 10, 100%) participants who agreed clinical criteria were consistent with nail psoriasis; no mismatched severity levels; and training photographs were realistic representations. All PGA-F items were locally independent and targeted patients along the severity continuum with complementary precision (item fit statistics: < the 1.5 acceptability threshold; exact agreements among the dermatologists [44%] and trial investigators [61.5%] exceeded 40% of acceptability threshold). Clinician reliability exceeded the threshold of acceptability for dermatologists and clinical trial investigators: 0.85 and 0.73, respectively. There was adequate correlation (>0.30) between mNAPSI and PGA-F at baseline and Week 26 with significant discrimination of severity and monotonic increases in the mNAPSI for each level of categorical severity on the PGA-F. ICC results for each type of IRR indicate that clinicians were consistent in individual patient ratings. CONCLUSION: The PGA-F is a rapid, valid and reliable clinician-rated severity scale for use in clinical practice and research.

Multidimensional daily diary of fatigue-fibromyalgia-17 items (MDF-fibro-17): part 2 psychometric evaluation in fibromyalgia patients.

BACKGROUND: The Multidimensional Daily Diary of Fatigue-Fibromyalgia-17 instrument (MDF-Fibro-17) has been developed for use in fibromyalgia (FM) clinical studies and includes 5 domains: Global Fatigue Experience, Cognitive Fatigue, Physical Fatigue, Motivation, and Impact on Function. Psychometric properties of the MDF-Fibro-17 needed to demonstrate the appropriateness of using this instrument in clinical studies are presented. METHODS: Psychometric analyses were conducted to evaluate the factor structure, reliability, validity, and responsiveness of the MDF-Fibro-17 using data from a Phase 2 clinical study of FM patients (N = 381). Confirmatory factor analyses (CFA) were performed to ensure understanding of the multidimensional domain structure, and a secondary factor analysis of the domains examined the appropriateness of calculating a total score in addition to domain scores. Longitudinal psychometric analyses (test-retest reliability and responder analysis) were also conducted on the data from Baseline to Week 6. RESULTS: The CFA supported the 17-item, 5 domain structure of this instrument as the best fit of the data: comparative fit index (CFI) and non-normed fit index (NNFI) were 0.997 and 0.992 respectively, standardized root mean square residual (SRMR) was 0.010 and the root mean square error of approximation (RMSEA) was 0.06. In addition, total score (CFI and NNFI both 0.95) met required standards. For the total and 5 domain scores, reliability and validity data were acceptable: test-retest and internal consistency were above 0.9; correlations were as expected with the Global Fatigue Index (GFI) (0.62-0.75), Fibromyalgia Impact Questionnaire (FIQ) Total (0.59-0.71), and 36-Item Short Form Health Survey (SF-36) vitality (VT) (0.43-0.53); and discrimination was shown using quintile scores for the GFI, FIQ Total, and Pain Numeric Rating Scale (NRS) quartiles. In addition, sensitivity to change was demonstrated with an overall mean responder score of -2.59 using anchor-based methods. CONCLUSION: The MDF-Fibro-17 reliably measures 5 domains of FM-related fatigue and psychometric evaluation confirms that this measure meets or exceeds each of the predefined acceptable thresholds for evidence of reliability, validity, and responsiveness to changes in clinical status. This suggests that the MDF-Fibro-17 is an appropriate and responsive measure of FM-related fatigue in clinical studies.

Development and psychometric evaluation of a novel tool for assessing patient perception and preference for haemophilia treatment (HaemoPREF).

Prophylactic use of treatment is important for good outcomes in haemophilia, yet adherence can be suboptimal. To better understand the relationship between treatment adherence and patients' beliefs about treatment there is a need to quantify patients' treatment attitudes. The aim of this study was to develop a brief, clinically relevant, patient-reported outcome (PRO) to measure ease of use and patients' preference for haemophilia treatment. A 40-item questionnaire was completed by male adults with haemophilia A from Austria, Germany, Italy, Spain and the UK. Robust statistical methods for item evaluation including item-level statistics, dimensionality analyses and input from clinical and outcomes experts were used to inform item reduction. Retained items were subjected to psychometric evaluation including exploratory factor analysis (EFA), known-groups validity and internal consistency reliability. 273 patients completed the questionnaire. Of the 40 items, 28 items were flagged for possible deletion based on item-level statistics, three of which were retained due to clinical relevance. Two items had acceptable statistical performance but were deleted based on low clinical relevance. A total of 13 items were retained. EFA produced a conceptually defined 5-factor solution. The survey had acceptable known-groups validity and internal consistency. Refinements were made to wording and scoring, and one new item was added to assess general ease of use, resulting in a 14-item questionnaire - the HaemoPREF. Preliminary measurement properties of the HaemoPREF support the instrument to evaluate patient perception and preference for haemophilia treatment. Further psychometric evaluation is required to examine and confirm the measurement properties of the scale.

Instability of simple sequence repeats in a mammalian cell line.

Short tandem repeat sequences in the mammalian genome are considered to be unstable, since many of them are polymorphic in length; however, the extent of this instability has been difficult to quantitate. We have directly determined the rate of mutation of a simple sequence repeat in a mammalian cell line. A plasmid containing a dinucleotide repeat [poly(CA/GT)] that disrupts the reading frame of a downstream gene was integrated into the genome of a mouse cell line, and spontaneous revertants were selected. Reversion rates were more than 100 times higher in cells carrying the repeated sequence than in control cells that carried the same fusion gene with a 4-bp out-of-frame deletion. Revertant clones derived from the lines carrying the dinucleotide repeat had insertions or deletions of one or more repeat units.

Two cases of tension pneumopericardium following blunt chest injury.

Tension pneumopericardium is uncommon in blunt trauma, and only rare survivors have been reported. We report two patients who survived tension pneumopericardium following blunt trauma. Both patients experienced signs and symptoms of cardiac tamponade that were corrected by insertion of a subxyphoid pericardial tube. Both survived all injuries and returned to normal activities with normal neurologic function.