Use of the Bath Ankylosing Spondylitis Disease Activity Index in Patients With Psoriatic Arthritis With and Without Axial Disease.

OBJECTIVE: To evaluate whether the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is a responsive instrument in psoriatic arthritis (PsA) and whether it differentiates between axial and peripheral disease activity in PsA. METHODS: Individuals with PsA initiating therapy in a longitudinal cohort study based in the United States were included. Axial PsA (axPsA), most often also associated with peripheral disease, was defined as fulfillment of the Assessment of Spondyloarthritis international Society axial spondyloarthritis classification criteria or presence of axial disease imaging features. Baseline BASDAI, individual BASDAI items, patient global assessment, patient pain, and Routine Assessment of Patient Index Data 3, and score changes following therapy initiation were descriptively reported. Standardized response means (SRMs) were calculated as the mean change divided by the SD of the change. RESULTS: The mean (SD) baseline BASDAI score at the time of therapy initiation was 5.0 (2.2) among those with axPsA (n = 40) and 4.8 (2.0) among those with peripheral-only disease (n = 79). There was no significant difference in patient-reported outcome scores between the groups. The mean change for BASDAI was similar among axial vs peripheral disease (-0.75 vs -0.83). SRMs were similar across axial vs peripheral disease for BASDAI (-0.37 vs -0.44) and the individual BASDAI items. CONCLUSION: BASDAI has reasonable responsiveness in PsA but does not differentiate between axPsA and peripheral PsA. (ClinicalTrials.gov: NCT03378336).

A comparison of physical function instruments in psoriatic arthritis: HAQ-DI vs MDHAQ vs PROMIS10 global physical health.

OBJECTIVES: Physical function is a core outcome in PsA. We examined the construct validity and responsiveness of three commonly used instruments to assess physical function in PsA: HAQ disability index (HAQ-DI), MultiDimensional HAQ (MDHAQ) and the Patient-Reported Outcomes Measurement Information System (PROMIS®) Global-10. METHODS: Between 2016 and 2019, patients with PsA were enrolled in the Psoriatic Arthritis Research Consortium longitudinal cohort study in the USA. Correlations were calculated at baseline and among change scores using Spearman's correlation coefficient. Standardized response means were calculated. Agreement with the 20% improvement cut-off was used to determine the potential effect of using MDHAQ or the PROMIS Global-10 physical health (GPH) subscore in place of HAQ-DI when assessing the ACR20. RESULTS: A total of 274 patients were included in the analysis. The mean age of patients was 49 years and 51% were male. At baseline, the mean HAQ-DI was 0.6 (s.d. 0.6; range 0-3), the mean MDHAQ was 1.8 (s.d. 1.6; range 0-10) and the mean GPH T-score was 43.4 (s.d. 9.3; range 0-100). All three instruments were strongly correlated at baseline (rho 0.75-0.85). Change scores were moderately correlated (rho 0.42-0.71). Among therapy initiators, the mean change between two visits in HAQ-DI, MDHAQ and GPH was -0.1 (s.d. 0.4), -0.2 (s.d. 1.2) and 2.5 (s.d. 6.1), respectively. The standardized response means were 0.18, 0.16 and 0.41, respectively. CONCLUSION: The three instruments tested are not directly interchangeable but have overall similar levels of responsiveness.

Anxiety impacts rheumatoid arthritis symptoms and health-related quality of life even at low levels.

OBJECTIVES: We explored the burden of symptoms of anxiety and depression on health-related quality of life (HRQL) in patients with rheumatoid arthritis (RA). METHODS: Adults with RA participating in an observational cohort completed PROMIS tests of depression, anxiety, fatigue, physical function (PF), pain interference (PI), sleep disturbance, and participation in social roles and activities at the baseline visit. Clinical measures of disease status were also obtained. We used ANOVA and partial correlation adjusting for the swollen joint count (SJC) to examine associations of anxiety and depression with other aspects of HRQL. Mild and moderate-severe anxiety were defined as T-scores ≥55.4 and ≥ 62.3 and mild and moderate-severe depression was defined as ≥52.5 and ≥58.6 based on previous validated clinical thresholds. Multivariable linear regression (MVR) was used to identify predictors of emotional distress with a subset analysis of those in remission/low disease activity. RESULTS: Of 196 RA participants, 18% had mild anxiety, 9% had moderate-severe anxiety, 18% had mild depression, and 14% had moderate-severe depression symptoms. Anxiety and depression scores were associated with significantly worse mean scores across HRQL domains (p <0.05). In MVR, depression (ß=0.75, p<0.001), PF (ß=0.14, p=0.024) and fatigue (ß=0.15, p=0.015) predicted higher anxiety levels, whereas only anxiety predicted higher depression levels (ß=0.70, p=<0.001). In subset analysis, PF no longer predicted higher anxiety levels. CONCLUSIONS: Emotional distress is common in RA, even when disease is well controlled, with considerable impacts on other aspects of HRQL even at mild levels.

A 64-year-old man with chronic obstructive pulmonary disease and an atypical rash.

A 64-year-old male patient with a 15-year history of chronic obstructive pulmonary disease presented with an atypical rash that was refractory to standard therapy. Pulmonary function tests confirmed an obstructive lung disease. Basic laboratory workup revealed conflicting information, leading to a diagnostic challenge discussed in this article. Ultimately, careful testing did reveal the diagnosis and the patient was treated accordingly.

What Does the Patient Global Health Assessment in Rheumatoid Arthritis Really Tell Us? Contribution of Specific Dimensions of Health-Related Quality of Life.

OBJECTIVE: To estimate the contributions of health-related quality of life domains to the patient global assessment of disease activity (PtGA) in rheumatoid arthritis (RA). METHODS: Data are drawn from baseline visits of 2 observational RA cohorts. Participants completed forms for patient-reported outcome measures, including PtGA and measures from the Patient-Reported Outcomes Measurement Information System, and clinical data were collected. Factor analysis was used to identify latent variables, and multivariable linear regression was used to estimate determinants of the PtGA. RESULTS: Patients were mostly female (81%), white (78%), and had established disease (mean ± SD 12.3 ± 10.7 years), with 62% in remission or having low disease activity. In cohort 1 (n = 196), the following 2 factors emerged: 1) daily function (moderate-to-strong [i.e., >|0.65|] loadings of physical function, pain interference, social participation, and fatigue, and weak [>0.35] loadings of sleep disturbance); and 2) emotional distress (strong loadings of depression and anxiety). In crude analysis, daily function explained up to 53% and emotional distress up to 20% of the variance in PtGA. In both cohorts, in adjusted analyses, daily function and, to a much lesser extent, swollen joint count independently predicted PtGA; age was inversely related to PtGA in cohort 1 only. CONCLUSION: These findings suggest that in patients with RA, PtGA ratings largely reflect the extent to which patients feel they can function in everyday roles and are not impacted by mood. This suggests that higher than expected PtGA scores may offer an opportunity to discuss patient expectations regarding roles and activities and the impact of their RA symptoms on daily function.

Advancing Stiffness Measurement in Rheumatic Disease: Report from the Stiffness Special Interest Group at OMERACT 2018.

OBJECTIVE: To improve measurement of stiffness in rheumatic disease. METHODS: Data presented included (1) 2 qualitative projects, (2) the rheumatoid arthritis (RA) stiffness patient-reported outcome measure (RAST), and (3) 3 items assessing stiffness severity, duration, and interference. RESULTS: Stiffness is multidimensional and includes aspects of stiffness experience such as duration, severity, and effect. Stiffness items showed construct validity in RA. Further efforts are required to develop an instrument that will be taken through the Outcome Measures in Rheumatology (OMERACT) Filter 2.1 for instrument selection. CONCLUSION: The research agenda for the group includes domain content voting for individual diseases, and development of stiffness item banks and disease-specific short forms.

Endorsement of the 66/68 Joint Count for the Measurement of Musculoskeletal Disease Activity: OMERACT 2018 Psoriatic Arthritis Workshop Report.

OBJECTIVE: The Psoriatic Arthritis (PsA) Core Domain Set for randomized controlled trials and longitudinal observational studies has recently been updated. The joint counts are central to the measurement of the peripheral arthritis component of the musculoskeletal (MSK) disease activity domain. We report the Outcome Measures in Rheumatology (OMERACT) 2018 meeting's approaches to seek endorsement of the 66/68 swollen and tender joint count (SJC66/TJC68) for inclusion in the PsA Core Outcome Measurement Set (COS). METHODS: Using the OMERACT Filter 2.1 Instrument Selection Process, the SJC66/TJC68 was assessed for (1) domain match, (2) feasibility, (3) numerical sense (construct validity), and (4) discrimination (test retest reliability, longitudinal construct validity, sensitivity in clinical trials, and thresholds of meaning). A protocol was designed to assess the measurement properties of the SJC66/TJC68 joint count. The results were summarized in a Summary of Measurement Properties table developed by OMERACT. OMERACT members discussed and voted on whether the strength of the evidence supported that the SJC66/TJC68 had passed the OMERACT Filter as an outcome measurement instrument for the PsA COS. RESULTS: OMERACT delegates endorsed the use of the SJC66/TJC68 for the measurement of the peripheral arthritis component of the MSK disease activity domain. Among patient research partners, 100% voted for a "green" endorsement, whereas among the group of other stakeholders, 88% voted for a "green" endorsement. CONCLUSION: The SJC66/TJC68 is the first fully endorsed outcome measurement instrument using the OMERACT Filter 2.1 and the first instrument fully endorsed within the PsA COS.

Summary of the International Multicenter Prospective Angioedema C1-inhibitor Trials 1 and 2 (IMPACT1 and 2).

Hereditary angioedema (HAE) is an autosomal dominant disease characterized by deficiency of C1 inhibitor (C1-INH) that commonly presents with recurrent swelling affecting different parts of the body. Supplementation with C1-INH is successfully used to treat HAE in selected countries, mostly in Europe. Berinert P (CSL Behring, Marburg, Germany), a human plasma-derived C1-INH, was studied in the International Multicenter Prospective Angioedema C1-inhibitor Trial 1 (IMPACT1) that was completed in 2007. It was the first safety and dose-finding study of C1-INH in patients with acute abdominal and facial angioedema. IMPACT2 was the extension of the first trial to study C1-INH efficacy and safety in multiple treatments of acute HAE attacks in various areas of the body. Berinert P has excellent potential to become a first-line therapy for treating patients with acute HAE attacks in the USA and other countries involved in the IMPACT trials. While final data from the IMPACT2 trial are not yet released, this article reviews currently available data from previous reports and abstract presentations.

Adverse events associated with intranasal influenza vaccine in the United States.

METHODS: The goal of this review was to analyze the post-vaccination adverse effects associated with Live Attenuated Influenza Vaccine (LAIV) compared to those of the Injectable Trivalent Inactivated Vaccine (TIV) in patients with egg allergy and asthma. PubMed, Ovid, and Google searches were conducted. Searched articles relating to allergic reactions, asthma or food allergy, and LAIV were reviewed. RESULTS: Similar or superior efficacy of LAIV compared to TIV was reported by various studies. Respiratory symptoms were the most common adverse events following both vaccinations. Although no evidence was found of a direct causal relationship between intranasal influenza vaccine and anaphylaxis due to egg allergy, a number of cases of anaphylaxis were reported. To date, there are no studies directly comparing the frequency of anaphylactic reactions between the two vaccines. CONCLUSIONS: The safety of LAIV in individuals with unstable asthma and egg allergy has not been established and it should be avoided in these populations. For patients with unstable asthma, TIV should remain the therapy of choice.

TrkB is necessary for pruning at the climbing fibre-Purkinje cell synapse in the developing murine cerebellum.

TrkB, the cognate receptor for brain-derived neurotrophic factor and neurotrophin-4, has been implicated in regulating synapse formation in the central nervous system. Here we asked whether TrkB plays a role in the maturation of the climbing fibre-Purkinje cell (CF-PC) synapse. In rodent cerebellum, Purkinje cells are initially innervated by multiple climbing fibres that are subsequently culled to assume the mature mono-innervated state, and whose contacts translocate from the soma to the dendrites. By employing transgenic mice hypomorphic or null for TrkB expression, our results indicated that perturbation of TrkB in the immature cerebellum resulted in ataxia, that Purkinje cells remained multiply innervated by climbing fibres beyond the normal developmental time frame, and that synaptic transmission at the parallel fibre-Purkinje cell synapse remained functionally unaltered. Mechanistically, we present evidence that attributes the persistence of multiple climbing fibre innervation to an obscured discrimination of relative strengths among competing climbing fibres. Soma-to-dendrite translocation of climbing fibre terminals was unaffected. Thus, TrkB regulates pruning but not translocation of nascent CF-PC synaptic contacts.