Patients' Perspectives on Shared Decision-Making About Medications in Psoriatic Arthritis: An Interview Study.

OBJECTIVE: Decision-making regarding medications to manage psoriatic arthritis (PsA) is complex because of multiple disease manifestations and comorbidities. Fear of side effects from systemic medications and misalignment in priorities between patients with PsA and rheumatologists makes shared decision-making challenging. We aimed to describe the perspectives of patients with PsA on shared decision-making regarding medication taking. METHODS: Face-to-face semistructured interviews were conducted with 25 adult patients with PsA in Australia. Transcripts were thematically analyzed. RESULTS: Five themes were identified: lacking agency in decision-making (denied choice, knowledge asymmetry, desperation and necessity, restricted by unfair eligibility criteria, automated approach); overwhelmed by potential harms (daunted by aggressive therapy, anticipating lifestyle disruption from side effects, jeopardizing fertility and pregnancy, avoiding relapse); gaining confidence (discernible benefit in function and mental health, sharpening knowledge over time, expertise of family and peers, empowered by information); opting for alternatives (pursuing normality, suspicion of over-medicalization, seeking comprehensive solutions); and developing trust and fortifying collaboration (assurance through a personable approach, seeking consistency, supported in decisional power, resolution through respectful negotiation). CONCLUSION: Patients with PsA lack agency in making treatment decisions and are overwhelmed by the potential harms of systemic medication. Improving knowledge and trust with medical teams in a supportive and collaborative environment, and strategies for managing risks and side effects may improve decision-making about pharmacologic management of PsA.

Correlation of patient-reported routine assessment of patient index data with clinical measures of disease activity in psoriatic arthritis.

AIM: A treat-to-target strategy is recommended for management of psoriatic arthritis (PsA), although there is lack of agreement regarding the best measure of disease activity to target. Physician assessments included in traditional indices can be complex and time consuming to complete and cannot be readily conducted by telehealth. This study compares the routine assessment of patient index data 3 (RAPID3), an efficient tool comprising patient self-assessment, with traditional clinician-led composite measures in the PsA clinic setting. METHODS: Data were collected prospectively from July 2016 to March 2020 in 2 dedicated PsA clinics in Sydney, Australia. A receiver operating characteristic (ROC) curve was created for comparison of RAPID3 score with composite scores minimal disease activity (MDA), very low disease activity (VLDA) and disease activity in psoriatic arthritis (DAPSA) in low disease activity or remission. RESULTS: Ninety-three patients had simultaneous collection of RAPID3 and MDA measures. Mean (SD) age was 49.9 (13.5) years, 50.5% were male and 23 (24.7%) had erosive disease at baseline. RAPID3 scores ≤3.2 and ≤2.7 (range 0-30) had high sensitivity and specificity for VLDA and DAPSA remission respectively, with ROC curve area under the curve (95% CI) of 0.94 (0.91-0.97) and 0.96 (0.93-0.99). CONCLUSION: RAPID3 has good agreement with physician-led composite scores of MDA, VLDA and DAPSA, and provides a viable alternative to composite scores. This is particularly helpful in settings that do not allow for clinical examination, for example telehealth.

Preferences for Biologic Treatment in Patients With Psoriatic Arthritis: A Discrete Choice Experiment.

OBJECTIVE: We aimed to assess patient preferences for the characteristics and outcomes of biologic and targeted synthetic disease-modifying antirheumatic drugs (DMARDs) to manage psoriatic arthritis. METHODS: We conducted a discrete choice experiment in patients with psoriatic arthritis from 3 rheumatology centers in Sydney, Australia. We assessed preferences for different attributes of biologic medications. The route and frequency of medications had a range of 5 levels, and the following 7 attributes had a range of 3 levels: the ability to attend to normal activities, improvements in joint pain, enthesitis and skin disease, chance of disease remission, risk of infection, and risk of severe adverse events. Multinomial logit models including a latent class model were used to calculate preferences. RESULTS: Of the 150 participants, 58.3% were female, with a median age of 53.5 years. The attributes in order of preference using the ß coefficient in absolute values (95% confidence interval [95% CI]) were as follows: oral route compared to subcutaneous and intravenous routes (ß coefficient 1.00 [fixed parameter]), avoiding severe side effects (ß coefficient 0.72 [95% CI 0.50, 0.95]), increasing ability to attend to normal activities (ß coefficient 0.66 [95% CI 0.36, 0.96]), avoiding infections (ß coefficient 0.38 [95% CI 0.23, 0.53]), improvement in enthesitis pain (ß coefficient 0.28 [95% CI 0.20, 0.36]), improvement in psoriasis (ß coefficient 0.28 [95% CI 0.20, 0.36]), increasing chance of remission (ß coefficient 0.27 [95% CI 0.19, 0.36]), and improvement in joint pain (ß coefficient 0.26 [95% CI 0.00, 0.52]). CONCLUSION: When choosing biologic medications, patients with psoriatic arthritis preferred oral medications. Patients prioritized avoiding severe complications, maintaining the ability to attend to work and normal activities, and avoiding infection over clinical measures of efficacy.

Time Required to Create a Referral in Various Store-and-Forward Telemedicine Networks.

Store and forward telemedicine is used routinely in health care, but there is little published information about how such telemedicine systems are used. For example, an important aspect of the system's usability is the length of time it takes to submit a referral. Referral-submission times were measured in networks based on the Collegium Telemedicus system. In a 25-week period in 2018/2019, eight Collegium networks received a total of 1,649 clinical or educational cases submitted via the web interface. The time to prepare a referral was measured in 669 of these cases, in two different ways. An indirect measurement of the referral-preparation time was calculated as the interval between the user logging in, and the referral being submitted. A direct measurement of the referral-preparation time was calculated as the interval between the user opening the referral page and the referral being submitted to the server. The difference between the two measurements represents time spent by the user on other activities after logging in, before beginning the referral. The median referral-preparation time, measured directly, was 888 s (IQR 512-1765). The median of the differences between the two preparation times was 27s (IQR 8-146). The referral-preparation times in the eight networks were broadly similar, despite the differences in the nature of their operation (clinical or educational), and the types of case handled (single specialty or multi-specialty). Quantitative information about aspects of the user interface, such as the referral-preparation time, is important not only in the initial system design, but also in its subsequent development.

Differential expression and regulation of the non-integrin 37/67-kDa laminin receptor on peripheral blood leukocytes of healthy individuals and patients with rheumatoid arthritis.

The non-integrin 37/67-kDa laminin receptor (LAMR1) is a complex protein with diverse functions. LAMR1 is widely expressed in epithelial cells and recently it was reported on neutrophils and a subset of activated T cells. Ligation of LAMR1 on peripheral blood mononuclear cells (PBMC) downregulated LPS-induced TNFα production, suggesting immune functions. However, its expression on primary monocytes remain unknown. Interestingly, LAMR1 mRNA is downregulated in PBMC of patients with early rheumatoid arthritis (RA), and low gene expression is an independent predictor of poor response to anti-TNFα treatment, suggesting a role in RA pathogenesis. We found LAMR1 was constitutively expressed on all peripheral blood monocytes and a subset of B cells from healthy individuals and patients with RA and it was abundantly present in synovial tissue of patients with RA. On monocytes and synovial tissue lower levels of LAMR1 expression tended to correlate with increased disease activity scores. In vitro treatment of monocytes with IFNγ or IL-10 up-regulated surface LAMR1 in healthy individuals and patients with RA with greater effects observed in healthy individuals. Importantly, treatment with IFNγ significantly increased specific binding of monocytes to laminin-1. TNFα and IL-1ß caused marginal downregulation of LAMR1 in patients but effects in controls were variable. Taken together, constitutively expressed LAMR1 on monocytes is differentially regulated by pro-inflammatory and immune-regulatory cytokines suggesting LAMR1 may regulate the threshold and amplitude of their activation and migration. Decreased levels in patients with RA may indicate loss of this potentially critical homeostatic regulation thereby contributing to the excessive inflammation.

Environmental lead exposure and its relationship to traffic density among Senegalese children: a cross-sectional study.

Leaded-gasoline is probably the primary source of lead (Pb) exposure in Dakar (Senegal). The present cross-sectional study was undertaken to investigate the levels of Pb in Senegalese children and to present helpful data on the relationship between Pb levels and changes in biological markers of heme biosynthesis and oxidative stress. A total of 330 children, living since birth either in rural or urban areas (ie, Khombole (n = 162) and Dakar (n = 168), respectively) were included. During this cross-sectional study, the mean blood (B)-Pb level in all children was 7.32 +/- 5.33 microg/dL, and was influenced by the area of residence and gender. In rural children, 27 subjects (16.7%), 18 boys (19.6%) and nine girls (12.9%), had a B-Pb level > 10 microg Pb/dL, whereas 99 urban children (58.9%), respectively, 66 boys (71.8%) and 33 girls (43.4%), had alarmingly high B-Pb levels. Accordingly, urine delta-aminolevulinic acid levels were higher in children living in the urban area than in the rural areas (P < 0.001), and closely correlated with the B-Pb levels (P < 0.01). Moreover, glutathione peroxidase (GPx) activity, selenium (Se) level, glutathione reductase (GR) activity, and glutathione status were significantly influenced by area of residence and/or by gender. GPx activity and Se level were not only negatively correlated with B-Pb levels, but also positively correlated together (P < 0.01). Taken together, the present results allow us to conclude that urban children have higher B-Pb levels than rural children, and that of these children, boys have higher B-Pb levels than girls, leading thereby to alterations of heme biosynthesis and pro-oxidant/antioxidant balance. We also suggest that exposure to Pb and the Pb-induced adverse effects merits attention and that the development of preventive actions are of increasing importance in Senegal.

Termination of immune activation: an essential component of healthy host immune responses.

The ideal immune response is rapid, proportionate and effective. Crucially, it must also be finite. An inflammatory response which is disproportionate or lasts too long risks injury to the host; chronic un-regulated inflammation in autoimmune diseases is one example of this. Thus, mechanisms to regulate and ultimately terminate immune responses are central to a healthy immune system. Despite extensive knowledge of what drives immune responses, our understanding of mechanisms of immune termination remains relatively sparse. It is clear that such processes are more complex than a one-dimensional homeostatic balance. Recent discoveries have revealed ever more nuanced mechanisms of signal termination, such as intrinsically self-limiting signals, multiple inhibitory mechanisms acting in tandem and activating proteins behaving differently in a variety of contexts. This review will summarise some important mechanisms, including termination by immunoreceptor tyrosine-based inhibitory motifs (ITIM), inhibition by soluble antagonists, receptor endocytosis or ubiquitination, and auto-inhibition by newly synthesised intracellular inhibitory molecules. Several recent discoveries showing immunoreceptor tyrosine-based activation motifs transducing inhibitory signals, ITIM mediating activating responses and the possible roles of immunoreceptor tyrosine-based switch motifs will also be explored.