Interpreting patient-reported outcomes in rheumatology

Patient-reported outcomes (PROs) have taken a central role in the evaluation of disease status and treatment effects in the rheumatic diseases. The aim of this thesis was to explore several contemporary issues related to the patient’s perspective and the use of modern psychometric analysis of PROs in rheumatology

Targeting and activation of Rac1 are mediated by the exchange factor β-Pix

Rho guanosine triphosphatases (GTPases) are critical regulators of cytoskeletal dynamics and control complex functions such as cell adhesion, spreading, migration, and cell division. It is generally accepted that localized GTPase activation is required for the proper initiation of downstream signaling events, although the molecular mechanisms that control targeting of Rho GTPases are unknown. In this study, we show that the Rho GTPase Rac1, via a proline stretch in its COOH terminus, binds directly to the SH3 domain of the Cdc42/Rac activator β-Pix (p21-activated kinase [Pak]–interacting exchange factor). The interaction with β-Pix is nucleotide independent and is necessary and sufficient for Rac1 recruitment to membrane ruffles and to focal adhesions. In addition, the Rac1–β-Pix interaction is required for Rac1 activation by β-Pix as well as for Rac1-mediated spreading. Finally, using cells deficient for the β-Pix–binding kinase Pak1, we show that Pak1 regulates the Rac1–β-Pix interaction and controls cell spreading and adhesion-induced Rac1 activation. These data provide a model for the intracellular targeting and localized activation of Rac1 through its exchange factor β-Pix

Subjective Cognitive Dysfunction in Patients With and Without Fibromyalgia:Prevalence, Predictors, Correlates, and Consequences

Background: Subjective cognitive dysfunction (SCD) is common in fibromyalgia (FM), where it has been called 'fibrofog.' But its predictors and correlates are not well understood, including the extent to which SCD is present in fibromyalgia and non-fibromyalgia clinical populations. In addition, there are no studies available concerning SCD and fibromyalgia in the general population. We investigated these issues in a longitudinal rheumatic disease research databank and two cross-sectional general population studies. Methods: 11,150 unselected patients with rheumatoid arthritis completed an assessment of FM and cognitive severity (CS) status using the full 0-3 fibromyalgia 2016 criteria assessment. In addition, CS was dummy coded as present/absent (CS+). Assessments of SCD and fibromyalgia prevalence were available in two German general population studies. Results: Fibromyalgia was present (FM+) in 2,493 (21.7%) of clinical subjects and absent (FM-) in 9,017 (78.3%) by FM 2016 criteria. Cognitive severity was present in 1,304 (52.3%) of those with fibromyalgia and 1,009 (11.2%) of non-fibromyalgia subjects (FM-). In two general population studies, 42.0% to 52.3% of those with fibromyalgia were CS+ as were 1.4% to 5.5% of FM- subjects. Patients with CS+ had more abnormal scores for every measure of rheumatoid arthritis (RA) severity, fibromyalgia severity, and general health. The presence of CS+ was strongly related to somatic and non-somatic symptoms scores and less strongly to pain variables. The best predictor of CS+ in the clinic and the general population was the symptom severity scale (SSS), a criterion of fibromyalgia. Conclusions: Persons with SCD have high counts of somatic and psychological symptoms. Subjective cognitive dysfunction is best predicted by a simple symptoms score, and not by pain extent scores. Although SCD is called fibrofog in patients with FM, 43.6% of CS+ cases occurred in FM- subjects. Fibromyalgia and CS are correlated but appear to be different parts of a symptom severity continuum. 'Fibrofog' as a phenomenon linked only to fibromyalgia is a misnomer because it can be identified in many non-fibromyalgia patients as well

Development and validation of the forms of self-criticizing / attacking and self-reassuring scale - Short form.

Studies investigating the effectiveness of compassion-focused therapy (CFT) are growing rapidly. As CFT is oriented toward helping people deal with internal processes of self-to-self-relating, having instruments to measure these processes is important. The 22-item Forms of Self-Criticizing/Attacking and Self-Reassuring Scale (FSCRS) has been found a useful measure. In the present study, a 14-item short form of the FSCRS (FSCRS-SF) suited to studies requiring brief measures was developed and tested in a Dutch community sample (N = 363), and cross-validated in a sample consisting of participants in a study on the effectiveness of a guided self-help compassion training (N = 243). Confirmatory factor analysis (CFA) indicated acceptable to good fit of the FSCRS-SF items to a three-factor model. Findings regarding internal consistency were inconsistent, with Study 1 showing adequate internal consistency for all subscale scores and Study 2 demonstrating satisfactory internal consistency only for the reassured self (RS) subscale score. Furthermore, the results showed that the FSCRS-SF subscale scores had adequate test–retest reliability and satisfactory convergent validity estimates with theoretically related constructs. In addition, the FSCRS-SF subscale scores were found to be sensitive to changes in self-to-self relating over time. Despite mixed findings regarding its reliability requiring further investigation, the FSCRS-SF offers a valid and sensitive measure which shows promise as a complimentary shorter version to the original FSCRS suited to nonclinical populations. Given that the FSCRS is increasingly used as a process and outcome measure, further research on this short form in nonclinical and clinical populations is warranted.N/

Measurement properties of physical function scales validated for use in patients with rheumatoid arthritis: A systematic review of the literature

Background:\ud The aim of this study was to systematically review the content validity and measurement properties of all physical function (PF) scales which are currently validated for use with patients with rheumatoid arthritis (RA). \ud \ud Methods:\ud Systematic literature searches were performed in the Scopus and PubMed databases to identify articles on the development or psychometric evaluation of PF scales for patients with RA. The content validity of included scales was evaluated by linking their items to the International Classification of Functioning Disability and Health (ICF). Furthermore, available evidence of the reliability, validity, responsiveness, and interpretability of the included scales was rated according to published quality criteria. \ud \ud Results:\ud The search identified 26 questionnaires with PF scales. Ten questionnaires were rated to have adequate content validity. Construct validity, internal consistency, test-retest reliability and responsiveness was rated favourably for respectively 15, 11, 5, and 6 of the investigated scales. Information about the absolute measurement error and minimal important change scores were rarely reported. \ud \ud Conclusion:\ud Based on this literature review, the disease-specificHAQ and the generic SF-36 can currently be most confidently recommended to measure PF in RA for most research purposes. The HAQ, however, was frequently associated with considerable ceiling effects while the SF-36 has limited content coverage. Alternative scales that might be better suited for specific research purposes are identified along with future directions for research