The impact of psoriasis on wellbeing and clinical outcomes in juvenile psoriatic arthritis

Objectives: Juvenile psoriatic arthritis (JPsA) has varied clinical features that are distinctive to other juvenile idiopathic arthritis (JIA) categories. This study investigates whether such features impact patient-reported and clinical outcomes. // Methods: Children and young people (CYP) were selected if recruited to the Childhood Arthritis Prospective Study, a UK multicentre JIA inception cohort, between January 2001 and March 2018. At diagnosis, patient/parent-reported outcomes (as age-appropriate) included the parental global assessment (10 cm VAS), functional ability (CHAQ), pain (10 cm VAS), health-related quality of life (CHQ psychosocial score), mood/depressive symptoms (MFQ) and parent psychosocial health (GHQ). Three-year outcome trajectories have previously been defined using active joint counts, physician and parent global assessments (PGA, PaGA respectively). Patient-reported outcomes and outcome trajectories were compared in i) CYP with JPsA versus other JIA categories, ii) CYP within JPsA, with and without psoriasis via multivariable linear regression. // Results: There were no significant differences in patient-reported outcomes at diagnosis between CYP with JPsA and non-JPsA. Within JPsA, those with psoriasis had more depressive symptoms (coefficient = 9.8, 95% CI = 0.5–19.0) than those without psoriasis at diagnosis. CYP with JPsA had 2.3 times the odds of persistent high PaGA than other ILAR categories, despite improving joint counts and PGA (95% CI 1.2, 4.6). // Conclusion: CYP with psoriasis at JPsA diagnosis report worse mood, supporting a greater disease impact in those with both skin and joint involvement. Multidisciplinary care with added focus to support wellbeing in children with JPsA plus psoriasis may help improve these outcomes

Trends in paediatric rheumatology referral times and disease activity indices over a ten-year period among children and young people with Juvenile Idiopathic Arthritis: results from the childhood arthritis prospective Study

OBJECTIVES: The medical management of JIA has advanced significantly over the past 10 years. It is not known whether these changes have impacted on outcomes. The aim of this analysis was to identify and describe trends in referral times, treatment times and 1-year outcomes over a 10-year period among children with JIA enrolled in the Childhood Arthritis Prospective Study. METHODS: The Childhood Arthritis Prospective Study is a prospective inception cohort of children with new-onset inflammatory arthritis. Analysis included all children recruited in 2001–11 with at least 1 year of follow-up, divided into four groups by year of diagnosis. Median referral time, baseline disease pattern (oligoarticular, polyarticular or systemic onset) and time to first definitive treatment were compared between groups. Where possible, clinical juvenile arthritis disease activity score (cJADAS) cut-offs were applied at 1 year. RESULTS: One thousand and sixty-six children were included in the analysis. The median time from symptom onset and referral to first paediatric rheumatology appointment (22.7–24.7 and 3.4–4.7 weeks, respectively) did not vary significantly (∼20% seen within 10 weeks of onset and ∼50% within 4 weeks of referral). For oligoarticular and polyarticular disease, 33.8–47 and 25.4–34.9%, respectively, achieved inactive disease by 1 year, with ∼30% in high disease activity at 1 year. A positive trend towards earlier definitive treatment reached significance in oligoarticular and polyarticular pattern disease. CONCLUSION: Children with new-onset JIA have a persistent delay in access to paediatric rheumatology care, with one-third in high disease activity at 1 year and no significant improvement over the past 10 years. Contributing factors may include service pressures and poor awareness. Further research is necessary to gain a better understanding and improve important clinical outcomes

Right ventricular free wall longitudinal strain is independently associated with mortality in mechanically ventilated patients with COVID-19

Background: Right ventricular (RV) dysfunction has been commonly reported in patients with Coronavirus disease 2019 (COVID-19), and is associated with mortality in mixed cohorts of patients requiring and not requiring invasive mechanical ventilation (IMV). Using RV-speckle tracking echocardiography (STE) strain analysis, we aimed to identify the prevalence of RV dysfunction (diagnosed by abnormal RV-STE) in patients with COVID-19 that are exclusively undergoing IMV, and assess association between RV dysfunction and 30 day mortality. We performed a prospective multicentre study across 10 ICUs in Scotland from 2/9/20 to 22/3/21. One-hundred-and-four echocardiography scans were obtained from adult patients at a single timepoint between 48 h after intubation, and day 14 of intensive care unit admission. We analysed RV-STE using RV free-wall longitudinal strain (RVFWLS), with an abnormal cutoff of  > −20%. We performed survival analysis using Kaplan–Meier, log rank, and multivariate cox-regression (prespecified covariates were age, gender, ethnicity, severity of illness, and time since intubation). Results: Ninety-four/one-hundred-and-four (90.4%) scans had images adequate for RVFWLS. Mean RVFWLS was −23.0% (5.2), 27/94 (28.7%) of patients had abnormal RVFWLS. Univariate analysis with Kaplan–Meier plot and log-rank demonstrated that patients with abnormal RVFWLS have a significant association with 30-day mortality (p = 0.047). Multivariate cox-regression demonstrated that abnormal RVFWLS is independently associated with 30-day mortality (Hazard-Ratio 2.22 [1.14–4.39], p = 0.020). Conclusions: Abnormal RVFWLS (> −20%) is independently associated with 30-day mortality in patients with COVID-19 undergoing IMV. Strategies to prevent RV dysfunction, and treatment when identified by RVFWLS, may be of therapeutic benefit to these patients. Trial Registration: Retrospectively registered 21st Feb 2021. ClinicalTrials.gov Identifier: NCT04764032

Validity of a three-variable juvenile arthritis disease activity score in children with new-onset juvenile idiopathic arthritis

<p>Objectives To investigate the validity and feasibility of the Juvenile Arthritis Disease Activity Score (JADAS) in the routine clinical setting for all juvenile idiopathic arthritis (JIA) disease categories and explore whether exclusion of the erythrocyte sedimentation rate (ESR) from JADAS (the ‘JADAS3’) influences correlation with single markers of disease activity.</p> <p>Methods JADAS-71, JADAS-27 and JADAS-10 were determined at baseline for an inception cohort of children with JIA in the Childhood Arthritis Prospective Study. JADAS3-71, JADAS3-27 and JADAS3-10 were determined using an identical formula but with exclusion of ESR. Correlation of JADAS with JADAS3 and single measures of disease activity/severity were determined by category.</p> <p>Results Of 956 eligible children, sufficient data were available to calculate JADAS-71, JADAS-27 and JADAS-10 at baseline in 352 (37%) and JADAS3 in 551 (58%). The median (IQR) JADAS-71, JADAS-27 and JADAS-10 for all 352 children was 11 (5.9–18), 10.4 (5.7–17) and 11 (5.9–17.3), respectively. Median JADAS and JADAS3 varied significantly with the category (Kruskal–Wallis p=0.0001), with the highest values in children with polyarticular disease patterns. Correlation of JADAS and JADAS3 across all categories was excellent. Correlation of JADAS71 with single markers of disease activity/severity was good to moderate, with some variation across the categories. With the exception of ESR, correlation of JADAS3-71 was similar to correlation of JADAS-71 with the same indices.</p> <p>Conclusions This study is the first to apply JADAS to all categories of JIA in a routine clinical setting in the UK, adding further information about the feasibility and construct validity of JADAS. For the majority of categories, clinical applicability would be improved by exclusion of the ESR.</p&gt

Cardiac biomarkers and right ventricular dysfunction are independently associated with one year mortality in patients with COVID-19 receiving mechanical ventilation: a prospective cohort study

Background: The cardiac biomarkers N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin frequently are raised in patients with acute COVID-19. As a secondary analysis of the Right Ventricular Dysfunction in Ventilated Patients With COVID-19 study, we sought to determine the association between raised cardiac biomarkers and 1-year mortality in patients with COVID-19 receiving invasive mechanical ventilation (IMV). As an exploratory investigation, we combined point-of-care echocardiography and cardiac biomarker analyses to determine whether the biomarker signal represented a global or regional cardiac injury. Study Question: Are abnormal cardiac biomarker levels associated with 1-year mortality in patients with COVID-19 requiring IMV? Study Design and Methods: In this prospective cardiac biomarker and echocardiography study in patients with COVID-19 across 10 ICUs in the west of Scotland, patients underwent contemporaneous cardiac biomarker testing with point-of-care echocardiography between days 2 and 14 after intubation. Survival analyses was performed using univariable log-rank and multivariable Cox regression. Results: One hundred twenty-one patients were recruited between September 2, 2020, and March 22, 2021. At 1 year, 57.6% of patients (68 of 118) had died. Patients with abnormal NT-proBNP levels and patients with abnormal troponin levels showed a 1-year mortality incidence of 71.4% (50 of 70) and 80.4% (45 of 56), respectively. Both abnormal NT-proBNP and abnormal troponin levels were associated with 1-year mortality (P < .001 for both). Abnormal troponin level was associated with subjective right ventricular dysfunction (RVD; P = .003), and no association with subjective left ventricular dysfunction was found (P = .342). On multivariable analysis, abnormal NT-proBNP level, abnormal troponin level, and subjective RVD were associated independently with 1-year mortality (hazard ratios, 2.82 [95% CI, 1.19-6.67], 2.84 [95% CI, 1.44-5.62], and 2.09 [95% CI, 1.07-4.07], respectively). Interpretation: Abnormal NT-proBNP level, abnormal troponin level, and subjective RVD are associated independently with 1-year mortality in patients with COVID-19 receiving IMV. Cardiac biomarker testing and point-of-care echocardiography are available readily during ICU admission and may identify a group of patients who are at very high risk of poor outcomes

L-DOPA increases slow-wave sleep duration and selectively modulates memory persistence in older adults

INTRODUCTION: Millions of people worldwide take medications such as L-DOPA that increase dopamine to treat Parkinson's disease. Yet, we do not fully understand how L-DOPA affects sleep and memory. Our earlier research in Parkinson's disease revealed that the timing of L-DOPA relative to sleep affects dopamine's impact on long-term memory. Dopamine projections between the midbrain and hippocampus potentially support memory processes during slow wave sleep. In this study, we aimed to test the hypothesis that L-DOPA enhances memory consolidation by modulating NREM sleep. METHODS: We conducted a double-blind, randomised, placebo-controlled crossover trial with healthy older adults (65-79 years, n = 35). Participants first learned a word list and were then administered long-acting L-DOPA (or placebo) before a full night of sleep. Before sleeping, a proportion of the words were re-exposed using a recognition test to strengthen memory. L-DOPA was active during sleep and the practice-recognition test, but not during initial learning. RESULTS: The single dose of L-DOPA increased total slow-wave sleep duration by approximately 11% compared to placebo, while also increasing spindle amplitudes around slow oscillation peaks and around 1-4 Hz NREM spectral power. However, behaviourally, L-DOPA worsened memory of words presented only once compared to re-exposed words. The coupling of spindles to slow oscillation peaks correlated with these differential effects on weaker and stronger memories. To gauge whether L-DOPA affects encoding or retrieval of information in addition to consolidation, we conducted a second experiment targeting L-DOPA only to initial encoding or retrieval and found no behavioural effects. DISCUSSION: Our results demonstrate that L-DOPA augments slow wave sleep in elderly, perhaps tuning coordinated network activity and impacting the selection of information for long-term storage. The pharmaceutical modification of slow-wave sleep and long-term memory may have clinical implications. CLINICAL TRIAL REGISTRATION: Eudract number: 2015-002027-26; https://doi.org/10.1186/ISRCTN90897064, ISRCTN90897064