Clinically suspect arthralgia and rheumatoid arthritis: patients' perceptions of illness.

OBJECTIVES: Clinically suspect arthralgia (CSA) is an at-risk stage of rheumatoid arthritis (RA), in which patients experience symptoms and physical limitations. Perceptions of CSA-patients have remained largely unknown. Therefore, we aimed to map perceptions of CSA-patients and compare these to RA-patients. Additionally, we studied changes in perceptions in CSA over time. METHODS: Three hundred and ninety-nine consecutively included CSA-patients from the Leiden and Rotterdam CSA-cohorts and 100 recently diagnosed RA-patients from the Leiden Early Arthritis Clinic were included. Patients' illness perceptions (IP) were assessed using the Brief Illness Perception Questionnaire (BIPQ), consisting of 8 questions (scale 0-10; higher score indicating more negative IP) covering cognitive, emotional and comprehensibility domains, and one open question about causes of disease. IP were measured at baseline in both populations and during 2years follow-up in the CSA-cohorts. RESULTS: Total BIPQ-scores were comparable at CSA-presentation and RA-diagnosis (40±11 and 40±10; range 0-80). Comparing dimensions separately revealed that CSA-patients were less worried about physical complaints compared to RA-patients. However, CSA-patients were more negative about expected treatment-effect on symptoms. IP over time in CSA improved in patients without development of clinical arthritis (from 38±11 to 34±14; P=0.005) but remained similar in CSA-patients who progressed to arthritis/RA (mean 40 at both timepoints). CSA-patients mainly perceived physical strain and heredity as causes of their complaints. CONCLUSIONS: Although CSA-patients have not developed clinical arthritis, illness perceptions at CSA-presentation and RA-diagnosis are equally severe. Knowledge on worries and expectations may contribute to improving patient-contact and care in patients at risk of RA.

Effects of a Novel, Transdiagnostic, Hybrid Ecological Momentary Intervention for Improving Resilience in Youth (EMIcompass): Protocol for an Exploratory Randomized Controlled Trial.

BACKGROUND: Most mental disorders first emerge in youth and, in their early stages, surface as subthreshold expressions of symptoms comprising a transdiagnostic phenotype of psychosis, mania, depression, and anxiety. Elevated stress reactivity is one of the most widely studied mechanisms underlying psychotic and affective mental health problems. Thus, targeting stress reactivity in youth is a promising indicated and translational preventive strategy for adverse mental health outcomes that could develop later in life and for improving resilience. Compassion-focused interventions offer a wide range of innovative therapeutic techniques that are particularly amenable to being implemented as ecological momentary interventions (EMIs), a specific type of mobile health intervention, to enable youth to access interventions in a given moment and context in daily life. This approach may bridge the current gap in youth mental health care. OBJECTIVE: This study aims to investigate the clinical feasibility, candidate underlying mechanisms, and initial signals of the efficacy of a novel, transdiagnostic, hybrid EMI for improving resilience to stress in youth-EMIcompass. METHODS: In an exploratory randomized controlled trial, youth aged between 14 and 25 years with current distress, a broad Clinical High At-Risk Mental State, or the first episode of a severe mental disorder will be randomly allocated to the EMIcompass intervention (ie, EMI plus face-to-face training sessions) in addition to treatment as usual or a control condition of treatment as usual only. Primary (stress reactivity) and secondary candidate mechanisms (resilience, interpersonal sensitivity, threat anticipation, negative affective appraisals, and momentary physiological markers of stress reactivity), as well as primary (psychological distress) and secondary outcomes (primary psychiatric symptoms and general psychopathology), will be assessed at baseline, postintervention, and at the 4-week follow-up. RESULTS: The first enrollment was in August 2019, and as of May 2021, enrollment and randomization was completed (N=92). We expect data collection to be completed by August 2021. CONCLUSIONS: This study is the first to establish feasibility, evidence on underlying mechanisms, and preliminary signals of the efficacy of a compassion-focused EMI in youth. If successful, a confirmatory randomized controlled trial will be warranted. Overall, our approach has the potential to significantly advance preventive interventions in youth mental health provision. TRIAL REGISTRATION: German Clinical Trials Register DRKS00017265; https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00017265. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/27462.

Clinical Relevance and Management of "Pre-Interstitial Lung Disease".

Cellular level changes that lead to interstitial lung disease (ILD) may take years to become clinically apparent and have been termed preclinical ILD. Incidentally identified interstitial lung abnormalities (ILA) are increasingly being recognized on chest computed tomographic scans done as part of lung cancer screening and for other purposes. Many individuals found to have ILA will progress to clinically significant ILD. ILA are independently associated with greater risk of death, lung function decline, and incident lung cancer. Current management recommendations focus on identifying individuals with ILA at high risk of progression, through a combination of clinical and radiological features.

Serum miRNA Signature in Rheumatoid Arthritis and "At-Risk Individuals".

Background: MicroRNAs (miRNAs) are small non-coding RNAs which have been implicated as potential biomarkers or therapeutic targets in autoimmune diseases. This study examines circulatory miRNAs in RA patients and further investigates if a serum miRNA signature precedes clinical manifestations of disease in arthralgia or "at-risk individuals". Methods: Serum was collected from HC subjects (N = 20), RA patients (N = 50), and arthralgia subjects (N = 10), in addition to a subgroup of the RA patients post-methotrexate (MTX) (N = 18). The FirePlex miRNA Immunology-V2 panel was selected for multiplex analysis of 68 miRNAs in each sample. DNA intelligent analysis (DIANA)-mirPath and Ingenuity Pathway Analysis (IPA) software were used to predict pathways targeted by the dysregulated miRNAs. Results: 8 miRNA (miR-126-3p, let-7d-5p, miR-431-3p, miR-221-3p, miR-24-3p, miR-130a-3p, miR-339-5p, let-7i-5p) were significantly elevated in RA serum compared to HC (all p < 0.01) and 1 miRNA (miR-17-5p) was significantly lower in RA (p < 0.01). High specificity and sensitivity were determined by receiver operating characteristic (ROC) curve analysis. Both miR-339-5p and let-7i-5p were significantly reduced post-MTX (both p < 0.01). MiR-126-3p, let-7d-5p, miR-431-3p, miR-221-3p, miR-24-3p, miR-130a-3p were also significantly elevated in subjects "at risk" of developing RA (all p < 0.05) compared to HC. IPA analysis of this miRNA signature identified downstream targets including key transcription factors NF-κB, STAT-1, STAT-3, cytokines IL-1ß, TNF-α, and matrix-metalloproteases all importantly associated with RA pathogenesis. Conclusion: This study identified six miRNAs that are altered in both RA and "at-risk individuals," which potentially regulate key downstream pathways involved in regulating inflammation. These may have potential as predictive signature for disease onset and early progression.

Myeloid Dendritic Cells Are Enriched in Lymph Node Tissue of Early Rheumatoid Arthritis Patients but not in At Risk Individuals.

Lymph nodes (LNs) are highly organized structures where specific immune responses are initiated by dendritic cells (DCs). We investigated the frequency and distribution of human myeloid (mDCs) and plasmacytoid (pDCs) in LNs and blood during the earliest phases of rheumatoid arthritis (RA). We included 22 RA-risk individuals positive for IgM rheumatoid factor and/or anti-citrullinated protein antibodies, 16 biological-naïve RA patients and 8 healthy controls (HCs). DC subsets (CD1c+ mDCs and CD304+ pDCs) in LN tissue and paired peripheral blood were analyzed using flow cytometry and confocal microscopy. In blood of RA patients a significant decreased frequency of pDCs was found, with a similar trend for mDCs. In contrast, mDC frequencies were higher in RA compared with HCs and RA-risk individuals, especially in LN. Frequency of mDCs seemed higher in LNs compared to paired blood samples in all donors, while pDCs were higher in LNs only in RA patients. As expected, both mDCs and pDCs localized mainly in T-cell areas of LN tissue. In conclusion, compared with RA-risk individuals, mDCs and pDCs were enriched in the LN tissue of early-RA patients, while their frequency in RA-risk individuals was comparable to HCs. This may suggest that other antigen-presenting cells are responsible for initial breaks of tolerance, while mDCs and pDCs are involved in sustaining inflammation.

Clinical applicability of proposed algorithm for identifying individuals at risk for hereditary hematologic malignancies.

Multiple genes have been identified to cause hereditary predispositions to hematologic malignancies, and characterized by an increased risk to develop myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and/or aplastic anemia (AA). Referral algorithms for patients who may be at higher risk have been proposed, with limited data regarding applicability. Our study aimed to evaluate referral criteria on a population of MDS/AML/AA patients. Demographic information and medical history were obtained from 608 patients referred over a 9-month period. Median age at diagnosis was 67 years (56-73), 387 (64%) were male, and the majority of individuals (54.9%) had AML. Overall, 406 individuals (66.8%) had insufficient documentation to determine whether certain criteria were met. Two hundred and two (33.2%) individuals met at least one criteria for genetic counseling referral; however, only nine (4.5%) were referred. Increased documentation of personal and family history is necessary to better assess and validate the applicability of these criteria.

Role of the lung in individuals at risk of rheumatoid arthritis.

Antibody-positive (seropositive) rheumatoid arthritis (RA) is a complex multiphasic disease developing in genetically susceptible individuals following environmental challenges (such as smoking). RA-associated autoantibodies can develop several years before any clinical signs of joint inflammation, suggesting that triggering of this autoimmunity occurs outside the joints. Epidemiological, clinical, and molecular studies in seropositive individuals at risk for developing RA as well as in early untreated RA suggest a potential role for mucosal sites (especially lung mucosa) as RA-associated autoimmunity trigger sites. This chapter summarizes clinical and molecular studies supporting the lung as a central site for autoimmunity initiation in RA.

What can palindromic rheumatism tell us?

Palindromic rheumatism (PR) is a syndrome characterised by recurrent, self-resolving inflammatory attacks in and around the joints. An association between PR and rheumatoid arthritis (RA) has long been postulated; a significant proportion of PR patients eventually develop RA and the majority also have anti-CCP antibodies. Therefore, PR is often considered a prodrome of RA. However, the clinical and imaging phenotype of PR has several important distinctions from RA. This suggests that despite the similarities, distinct disease mechanisms are at play. Given the paucity of evidence-based therapy in PR, a better understanding of these mechanisms will be important for refined and targeted therapeutic approaches for this important condition.

'At-risk' individuals' responses to direct to consumer advertising of prescription drugs: a nationally representative cross-sectional study.

OBJECTIVES: The factors determining individuals' self-reported behavioural responses to direct to consumer advertising of prescription drugs were explored with an emphasis on 'at-risk' individuals' responses. DESIGN: Nationally representative cross-sectional survey. SETTING: Community living adults in New Zealand. PARTICIPANTS: 2057 adults (51% women). PRIMARY OUTCOME MEASURES: Self-reported behavioural responses to drug advertising (asking a physician for a prescription, asking a physician for more information about an illness, searching the internet for more information regarding an illness and asking a pharmacist for more information about a drug). METHODS: Multivariate logistic regressions determined whether participants' self-reported behavioural responses to drug advertising were predicted by attitudes towards advertising and drug advertising, judgements about safety and effectiveness of advertised drugs, self-reported health status, materialism, online search behaviour as well as demographic variables. RESULTS: Identifying as Indian and to a less extent Chinese, Maori and 'other' ethnicities were the strongest predictors of one or more self-reported responses (ORs 1.76-5.00, Ps<0.05). Poorer self-reported health status (ORs 0.90-0.94, all Ps<0.05), favourable attitude towards drug advertising (ORs 1.34-1.61, all Ps<0.001) and searching for medical information online (ORs 1.32-2.35, all Ps<0.01) predicted all self-reported behavioural outcomes. Older age (ORs 1.01-1.02, Ps<0.01), less education (OR 0.89, P<0.01), lower income (ORs 0.89-0.91, Ps<0.05) and higher materialism (ORs 1.02-1.03, Ps<0.01) also predicted one or more self-reported responses. CONCLUSIONS: Taken together, the findings suggest individuals, especially those who are 'at-risk' (ie, with poorer self-reported health status, older, less educated, lower income and ethnic minorities), may be more vulnerable to drug advertising and may make uninformed decisions accordingly. The outcomes raise significant concerns relating to the ethicality of drug advertising and suggest a need for stricter guidelines to ensure that drug advertisements provided by pharmaceutical companies are ethical.