Correction to: Role of Alpha-2-Microglobulin in the Treatment of Osteoarthritic Knee Pain: a Brief Review of the Literature.

The original publication listed author Alan Kaye as "A. Kaye," but his name should read "A.D. Kaye." The correct author name is presented in this article.

Role of Alpha-2-Microglobulin in the Treatment of Osteoarthritic Knee Pain: a Brief Review of the Literature.

PURPOSE OF REVIEW: Chronic knee pain remains a debilitating condition that remains difficult to manage. The purpose of this review, therefore, is to summarize current understanding of alpha-2-microglobulin in the treatment of osteoarthritic knee pain. Furthermore, we investigate its role in the anti-inflammatory properties of platelet-rich plasma (PRP). RECENT FINDINGS: Alpha-2-microglobulin, a 720-kD protein complex, is an active protease inhibitor with tremendous anti-inflammatory properties in animal models. A growing body of evidence suggests that this complex is the most instrumental factor for cartilage preservation in PRP injections. As an active component of platelet-rich plasma's anti-inflammatory properties, alpha-2-microglobulin has been shown to be an active inhibitor of joint degeneration, cartilage preservation, and improvement in quality of life for patients with knee osteoarthritis compared with a multitude of other modalities.

Membrane Stabilizer Medications in the Treatment of Chronic Neuropathic Pain: a Comprehensive Review.

PURPOSE OF REVIEW: Neuropathic pain is often debilitating, severely limiting the daily lives of patients who are affected. Typically, neuropathic pain is difficult to manage and, as a result, leads to progression into a chronic condition that is, in many instances, refractory to medical management. RECENT FINDINGS: Gabapentinoids, belonging to the calcium channel blocking class of drugs, have shown good efficacy in the management of chronic pain and are thus commonly utilized as first-line therapy. Various sodium channel blocking drugs, belonging to the categories of anticonvulsants and local anesthetics, have demonstrated varying degrees of efficacy in the in the treatment of neurogenic pain. Though there is limited medical literature as to efficacy of any one drug, individualized multimodal therapy can provide significant analgesia to patients with chronic neuropathic pain.

Feasibility and Construct Validation of the Patient Reported Outcomes Measurement Information System in Systemic Vasculitis.

OBJECTIVE: The Patient Reported Outcome Measurement Information System (PROMIS) is a collection of item banks of self-reported health. This study assessed the feasibility and construct validity of using PROMIS instruments in vasculitis. METHODS: Data from a multicenter longitudinal cohort of subjects with systemic vasculitis were used. Instruments from 10 PROMIS item banks were selected with direct involvement of patients. Subjects completed PROMIS instruments using computer adaptive testing (CAT). The Medical Outcomes Study Short Form-36 (SF-36) was also administered. Cross-sectional construct validity was assessed by calculating correlations of PROMIS scores with SF-36 measures and physician and patient global scores for disease activity. Longitudinal construct validity was assessed by correlations of between-visit differences in PROMIS scores with differences in other measures. RESULTS: During the study period, 973 subjects came for 2306 study visits and the PROMIS collection was completed at 2276 (99%) of visits. The median time needed to complete each PROMIS instrument ranged from 40 to 55 s. PROMIS instruments correlated cross-sectionally with individual scales of the SF-36, most strongly with subscales of the SF-36 addressing the same domain as the PROMIS instrument. For example, PROMIS fatigue correlated with both the physical component score (PCS; r = -0.65) and with the mental component score (MCS; r = -0.54). PROMIS physical function correlated strongly with PCS (r = 0.81) but weakly with MCS (r = 0.29). Weaker correlations were observed longitudinally between change in PROMIS scores with change in PCS and MCS. CONCLUSION: Collection of data using CAT PROMIS instruments is feasible among patients with vasculitis and has some cross-sectional and longitudinal construct validity.

Updating OMERACT Core Set of Domains for ANCA-associated Vasculitis: Patient Perspective Using the International Classification of Function, Disability, and Health.

OBJECTIVE: Aspects of antineutrophil cytoplasmic antibodies-associated vasculitis (AAV) prioritized by patients with AAV were described using the International Classification of Function, Disability, and Health (ICF). METHODS: Items identified during 14 individual interviews were incorporated into an ICF-based questionnaire administered to participants of 2 vasculitis patient symposia: 36 in the United Kingdom and 63 in the United States. RESULTS: Categories identified as at least "moderately relevant" by ≥ 5% of subjects included 44 body functions, 14 body structures, 35 activities and participation, 31 environmental factors, and 38 personal factors. CONCLUSION: Identified categories differ from those identified by the current Outcome Measures in Rheumatology (OMERACT) core set and those prioritized by vasculitis experts.

Validation of the ANCA-associated vasculitis patient-reported outcomes (AAV-PRO) questionnaire.

OBJECTIVES: To finalise and validate a disease-specific patient-reported outcome (PRO) measure: the ANCA-associated vasculitis patient-reported outcome (AAV-PRO) questionnaire. Using a 35-item candidate questionnaire developed following 50 qualitative interviews in the UK, USA and Canada, a longitudinal survey was conducted to determine the final scale structure and validate the AAV-PRO. METHODS: Participants were recruited via Vasculitis UK and the Vasculitis Patient-Powered Research Network. The 35-item candidate questionnaire was completed at baseline and 3 months; UK participants completed the EuroQol-5D-5L (EQ-5D-5L), while US participants completed a test-retest exercise, 3-5 days after baseline. Scale structure was defined using exploratory factor analysis (EFA) and Rasch analysis. Convergent and known groups validity, test-retest reliability and longitudinal construct validity were assessed. RESULTS: There were 626 participants with AAV; >25% reporting 'active disease'. EFA and Rasch analysis supported a 29-item profile measure comprising six domains: 'organ-specific symptoms', 'systemic symptoms', 'treatment side effects', 'social and emotional impact', 'concerns about the future' and 'physical function'. Mean domain scores were higher for participants with 'active disease' versus 'remission' (p<0.001). Construct validity was demonstrated by correlations between domain scores and the EQ-5D-5L (range r=-0.55 to 0.78), all p<0.0001. In participants reporting 'no change' (n=97) during the test-retest, intraclass correlation coefficient values were high (range 0.89-0.96) for each domain. CONCLUSIONS: The AAV-PRO, a new disease-specific PRO measure for AAV, has good face and construct validity, is reliable, feasible and discriminates among disease states.

Health-related quality of life in ANCA-associated vasculitis and item generation for a disease-specific patient-reported outcome measure.

OBJECTIVE: The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are multisystem diseases of the small blood vessels. Patients experience irreversible damage and psychological effects from AAV and its treatment. An international collaboration was created to investigate the impact of AAV on health-related quality of life (HRQoL), and develop a disease-specific patient-reported outcome measure to assess outcomes of importance to patients. METHODS: Patients with AAV from the UK, USA, and Canada were interviewed to identify salient aspects of HRQoL affected by AAV. The study was overseen by a steering committee including four patient research partners. Purposive sampling of interviewees ensured representation of a range of disease manifestations and demographics. Inductive analysis was used to identify themes of importance to patients; these were further confirmed by a free-listing exercise in the US. Individual themes were recast into candidate items, which were scrutinized by patients, piloted through cognitive interviews and received a linguistic and translatability evaluation. RESULTS: Fifty interviews, conducted to saturation, with patients from the UK, USA, and Canada, identified 55 individual themes of interest within seven broad domains: general health perceptions, impact on function, psychological perceptions, social perceptions, social contact, social role, and symptoms. Individual themes were constructed into >100 candidate questionnaire items, which were then reduced and refined to 35 candidate items. CONCLUSION: This is the largest international qualitative analysis of HRQoL in AAV to date, and the results have underpinned the development of 35 candidate items for a disease-specific, patient-reported outcome questionnaire.

Patient perceptions of glucocorticoids in anti-neutrophil cytoplasmic antibody-associated vasculitis.

Granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA) are multisystem diseases of small blood vessels, collectively known as the anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV). This study explores the patient's perspective on the use of glucocorticoids, which are still a mainstay of treatment in AAV. Patients with AAV from the UK, USA, and Canada were interviewed, using purposive sampling to include a range of disease manifestations and demographics. The project steering committee, including patient partners, designed the interview prompts and cues about AAV, its treatment, and impact on health-related quality of life. Interviews were transcribed and analysed to establish themes grounded in the data. A treatment-related code was used to focus analysis of salient themes related to glucocorticoid therapy. Fifty interviews were conducted. Individual themes related to therapy with glucocorticoids emerged from the data and were analysed. Three overarching themes emerged: (1) Glucocorticoids are effective at the time of diagnosis and during relapse, and withdrawal can potentiate a flare, (2) glucocorticoids are associated with salient emotional, physical, and social effects (depression, anxiety, irritation, weight gain and change in appearance, diabetes mellitus, effect on family and work); and (3) patient perceptions of balancing the risks and benefits of glucocorticoids. Patients identified the positive aspects of treatment with glucocorticoids; they are fast-acting and effective, but, they voiced concerns about adverse effects and the uncertainty of the dose-reduction process. These results may be informative in the development of novel glucocorticoid-sparing regimens.

OMERACT Endorsement of Patient-reported Outcome Instruments in Antineutrophil Cytoplasmic Antibody-associated Vasculitis.

OBJECTIVE: The antineutrophil cytoplasmic antibody-associated vasculitides (AAV) are multiorgan diseases. Patients with AAV report impairment in their health-related quality of life (HRQOL) and have different priorities regarding disease assessment compared with physicians. The Outcome Measures in Rheumatology (OMERACT) Vasculitis Working Group previously received endorsement for a core set of domains in AAV. Two approaches to measure patient-reported outcomes (PRO) were presented at OMERACT 2016. METHODS: A novel 5-step tool was used to facilitate assessment of the instruments by delegates: the OMERACT Filter 2.0 Instrument Selection Algorithm, with a red-amber-green checklist of questions, including (1) good match with domain (face and content validity), (2) feasibility, (3) do numeric scores make sense (construct validity)?, (4) overall ratings of discrimination, and (5) can individual thresholds of meaning be defined? Delegates gave an overall endorsement. Three generic Patient-Reported Outcomes Measurement Information System (PROMIS) instruments (fatigue, physical functioning, and pain interference) and a disease-specific PRO, the AAV-PRO (6 domains related to symptoms and HRQOL), were presented. RESULTS: OMERACT delegates endorsed the use of the PROMIS instruments for fatigue, physical functioning, and pain interference (87.6% overall endorsement) and the disease-specific AAV-PRO instrument (89.4% overall endorsement). CONCLUSION: The OMERACT Vasculitis Working Group gained endorsement by OMERACT for use of the PROMIS and the AAV-PRO in clinical trials of vasculitis. These instruments are complementary to each other. The PROMIS and the AAV-PRO need further work to assess their utility in longitudinal settings, including their ability to discriminate between treatments of varying efficacy in the setting of a randomized controlled trial.

Exploration, Development, and Validation of Patient-reported Outcomes in Antineutrophil Cytoplasmic Antibody-associated Vasculitis Using the OMERACT Process.

OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of linked multisystem life- and organ-threatening diseases. The Outcome Measures in Rheumatology (OMERACT) vasculitis working group has been at the forefront of outcome development in the field and has achieved OMERACT endorsement of a core set of outcomes for AAV. Patients with AAV report as important some manifestations of disease not routinely collected through physician-completed outcome tools; and they rate common manifestations differently from investigators. The core set includes the domain of patient-reported outcomes (PRO). However, PRO currently used in clinical trials of AAV do not fully characterize patients' perspectives on their burden of disease. The OMERACT vasculitis working group is addressing the unmet needs for PRO in AAV. METHODS: Current activities of the working group include (1) evaluating the feasibility and construct validity of instruments within the PROMIS (Patient-Reported Outcome Measurement Information System) to record components of the disease experience among patients with AAV; (2) creating a disease-specific PRO measure for AAV; and (3) applying The International Classification of Functioning, Disability and Health to examine the scope of outcome measures used in AAV. RESULTS: The working group has developed a comprehensive research strategy, organized an investigative team, included patient research partners, obtained peer-reviewed funding, and is using a considerable research infrastructure to complete these interrelated projects to develop evidence-based validated outcome instruments that meet the OMERACT filter of truth, discrimination, and feasibility. CONCLUSION: The OMERACT vasculitis working group is on schedule to achieve its goals of developing validated PRO for use in clinical trials of AAV.