ColdZyme® Mouth Spray reduces duration of upper respiratory tract infection symptoms in endurance athletes under free living conditions

Upper respiratory tract infection (URTI) can compromise athlete preparation and performance, so countermeasures are desirable. The aim of this study was to assess the effects of ColdZyme® Mouth Spray (ColdZyme) on self-reported upper respiratory tract infection in competitive endurance athletes under free-living conditions. One hundred and twenty-three endurance-trained, competitive athletes (recruited across 4 sites in England, UK) were randomised to control (no treatment, n = 61) or ColdZyme (n = 62) for a 3-month study period (between December 2017 – February 2018; or December 2018 – April 2019). They recorded daily training and illness symptoms (Jackson common cold questionnaire) during the study period. A total of 130 illness episodes were reported during the study with no difference in incidence between groups (episodes per person: 1.1 ± 0.9 Control, 1.0 ± 0.8 ColdZyme, P = 0.290). Episode duration was significantly shorter in ColdZyme compared to Control: Control 10.4 ± 8.5 days vs ColdZyme 7.7 ± 4.0 days, P = 0.016). Further analysis to compare episodes with poor vs good compliance with ColdZyme instructions for use (IFU) within the ColdZyme group showed a further reduction in duration of URTI when compliance was good (9.3 ± 4.5 days in ColdZyme poor IFU compliance vs 6.9 ± 3.5 days in ColdZyme good IFU compliance, P = 0.040). ColdZyme may be an effective countermeasure to reduce URTI duration, which was significantly lower (by 26-34%) in the ColdZyme treatment group (with no influence on incidence). This may have implications for athlete performance

Real-world comparison of the effects of etanercept and adalimumab on well-being in non-systemic juvenile idiopathic arthritis: a propensity score matched cohort study

Background: Etanercept (ETN) and adalimumab (ADA) are considered equally efective biologicals in the treat‑ ment of arthritis in juvenile idiopathic arthritis (JIA) but no studies have compared their impact on patient-reported well-being. The objective of this study was to determine whether ETN and ADA have a diferential efect on patientreported well-being in non-systemic JIA using real-world data. Methods: Biological-naive patients without a history of uveitis were selected from the international Pharmachild registry. Patients starting ETN were matched to patients starting ADA based on propensity score and outcomes were collected at time of therapy initiation and 3–12 months afterwards. Primary outcome at follow-up was the improve‑ ment in Juvenile Arthritis Multidimensional Assessment Report (JAMAR) visual analogue scale (VAS) well-being score from baseline. Secondary outcomes at follow-up were decrease in active joint count, adverse events and uveitis events. Outcomes were analyzed using linear and logistic mixed efects models. Results: Out of 158 eligible patients, 45 ETN starters and 45 ADA starters could be propensity score matched result‑ ing in similar VAS well-being scores at baseline. At follow-up, the median improvement in VAS well-being was 2 (inter‑ quartile range (IQR): 0.0 – 4.0) and scores were signifcantly better (P=0.01) for ETN starters (median 0.0, IQR: 0.0 – 1.0) compared to ADA starters (median 1.0, IQR: 0.0 – 3.5). The estimated mean diference in VAS well-being improvement from baseline for ETN versus ADA was 0.89 (95% CI: -0.01 – 1.78; P=0.06). The estimated mean diference in active joint count decrease was -0.36 (95% CI: -1.02 – 0.30; P=0.28) and odds ratio for adverse events was 0.48 (95% CI: 0.16 –1.44; P=0.19). One uveitis event was observed in the ETN group. Conclusions: Both ETN and ADA improve well-being in non-systemic JIA. Our data might indicate a trend towards a slightly stronger efect for ETN, but larger studies are needed to confrm this given the lack of statistical signifcance

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Prevalence of familial autoimmune diseases in juvenile idiopathic arthritis: results from the international Pharmachild registry

Background Little is known about the disposition to autoimmune diseases (ADs) among children diagnosed with JIA. In this study, we provide a comprehensive overview of the prevalence of and factors associated with ADs in parents of children with juvenile idiopathic arthritis (JIA). Methods Prevalence rates of ADs and 95% Poisson confidence intervals were calculated for parents of JIA patients from the international Pharmachild registry and compared with general population prevalence rates as reported in the literature. Demographic, clinical and laboratory features were compared between JIA patients with and without a family history of AD using chi(2) and Mann-Whitney U tests. Results Eight thousand six hundred seventy three patients were included and the most common familial ADs were psoriasis, autoimmune thyroid disease, rheumatoid arthritis and ankylosing spondylitis. The prevalence of several ADs was higher in parents of the included JIA patients than in the general population. Clinical Juvenile Arthritis Disease Activity Scores at study entry and last follow-up were not significantly different between patients with (n = 1231) and without a family history of AD (n = 7442). Factors associated with familial AD were older age at JIA onset (P < 0.01), Scandinavian residence (P < 0.01), enthesitis-related arthritis, psoriatic arthritis and undifferentiated arthritis (P < 0.01), ANA positivity (P = 0.03) and HLA-B27 positivity (P < 0.01). Conclusions Familial AD proves to be a risk factor for JIA development and certain diseases should therefore not be overlooked during family health history at the diagnosis stage. A family history of AD is associated with the JIA category but does not influence the severity or disease course

Burden of comorbid conditions in children and young people with juvenile idiopathic arthritis: a collaborative analysis of 3 JIA registries

OBJECTIVES: Burden of comorbidities are largely unknown in JIA. From 2000, national and international patient registries were established to monitor biologic treatment, disease activity and adverse events in patients with JIA. The aim of this analysis was to investigate in parallel, for the first time, three of the largest JIA registries in Europe/internationally—UK JIA Biologic Registers (BCRD/BSPAR-ETN), German biologic registers (BiKeR/JuMBO), multinational Pharmachild—to quantify the occurrence of selected comorbidities in patients with JIA. METHODS: Information on which data the registers collect were compared. Patient characteristics and levels of comorbidity were presented, focussing on four key conditions: uveitis, MAS, varicella, and history of tuberculosis. Incidence rates of these on MTX/biologic therapy were determined. RESULTS: 8066 patients were registered into the three JIA registers with similar history of the four comorbidities across the studies; however, varicella vaccination coverage was higher in Germany (56%) vs UK/Pharmachild (16%/13%). At final follow-up, prevalence of varicella infection was lower in Germany (15%) vs UK/Pharmachild (37%/50%). Prevalence of TB (0.1–1.8%) and uveitis (15–19%) was similar across all registers. The proportion of systemic-JIA patients who ever had MAS was lower in Germany (6%) vs UK (15%) and Pharmachild (17%). CONCLUSION: This analysis is the first and largest to investigate the occurrence of four important comorbidities in three JIA registries in Europe and the role of anti-rheumatic drugs. Combined, these three registries represent one of the biggest collection of cases of JIA worldwide and offer a unique setting for future JIA outcome studies

A clinical prediction model for estimating the risk of developing uveitis in patients with juvenile idiopathic arthritis

To build a prediction model for uveitis in children with JIA for use in current clinical practice

Increased incidence of inflammatory bowel disease on etanercept in juvenile idiopathic arthritis regardless of concomitant methotrexate use.

OBJECTIVES: To describe risk factors for inflammatory bowel disease (IBD) development in a cohort of children with juvenile idiopathic arthritis (JIA). METHODS: JIA patients who developed IBD were identified from the international Pharmachild register. Characteristics were compared between IBD and non-IBD patients and predictors of IBD were determined using multivariable logistic regression analysis. Incidence rates of IBD events on different disease-modifying anti-rheumatic drugs (DMARDs) were calculated, differences between therapies were expressed as relative risks (RR). RESULTS: Out of 8,942 patients, 48 (0.05\%) developed IBD. These were more often male (47.9\% vs 32.0\%) and HLA-B27 positive (38.2\% vs 21.0\%) and older at JIA onset (median 8.94 vs 5.33 years) than patients without IBD development. They also had more often a family history of autoimmune disease (42.6\% vs 24.4\%) and enthesitis-related arthritis (ERA) (39.6\% vs 10.8\%). The strongest predictors of IBD on multivariable analysis were ERA (OR: 3.68, 95\% CI: 1.41-9.40) and a family history of autoimmune disease (OR: 2.27, 95\% CI: 1.12-4.54). Compared with methotrexate monotherapy, the incidence of IBD on etanercept monotherapy (RR: 7.69, 95\% CI: 1.99-29.74), etanercept with methotrexate (RR: 5.70, 95\% CI: 1.42-22.77) and infliximab (RR: 7.61, 95\% CI: 1.27-45.57) therapy was significantly higher. Incidence on adalimumab was not significantly different (RR: 1.45, 95\% CI: 0.15-13.89). CONCLUSION: IBD in JIA was associated with ERA and a family history of autoimmune disease. An increased IBD incidence was observed for etanercept therapy regardless of concomitant methotrexate use

Phenotypic variability and disparities in treatment and outcomes of childhood arthritis throughout the world: an observational cohort study

Background To our knowledge, the characteristics and burden of childhood arthritis have never been studied on a worldwide basis. We aimed to investigate, with a cross-sectional study, the prevalence of disease categories, treatment methods, and disease status in patients from across different geographical areas and from countries with diverse wealth status

Phenotypic variability and disparities in treatment and outcomes of childhood arthritis throughout the world: an observational cohort study.

BACKGROUND:To our knowledge, the characteristics and burden of childhood arthritis have never been studied on a worldwide basis. We aimed to investigate, with a cross-sectional study, the prevalence of disease categories, treatment methods, and disease status in patients from across different geographical areas and from countries with diverse wealth status. METHODS: In this multinational, cross-sectional, observational cohort study, we asked international paediatric rheumatologists from specialised centres to enrol children with a diagnosis of juvenile idiopathic arthritis, according to International League of Associations for Rheumatology criteria, who were seen consecutively for a period of 6 months. Each patient underwent retrospective and cross-sectional assessments, including measures of disease activity and damage and questionnaires on the wellbeing and quality of life of the children. We qualitatively compared the collected data across eight geographical areas, and we explored an association between disease activity and damage and a country\u27s gross domestic product (GDP) with a multiple logistic regression analysis. FINDINGS: Between April 4, 2011, and Nov 21, 2016, 9081 patients were enrolled at 130 centres in 49 countries, grouped into eight geographical areas. Systemic arthritis (125 [33·0%] of 379 patients) and enthesitis-related arthritis (113 [29·8%] of 379) were more common in southeast Asia, whereas oligoarthritis was more prevalent in southern Europe (1360 [56·7%] of 2400) and rheumatoid factor-negative polyarthritis was more frequent in North America (165 [31·5%] of 523) than in the other areas. Prevalence of uveitis was highest in northern Europe (161 [19·1%] of 845 patients) and southern Europe (450 [18·8%] of 2400) and lowest in Latin America (54 [6·4%] of 849), Africa and Middle East (71 [5·9%] of 1209), and southeast Asia (19 [5·0%] of 379). Median age at disease onset was lower in southern Europe (3·5 years, IQR 1·9-7·3) than in other regions. Biological, disease-modifying antirheumatic drugs were prescribed more frequently in northern Europe and North America than in other geographical settings. Patients living in countries with lower GDP had greater disease activity and damage than those living in wealthier countries. Damage was associated with referral delay. INTERPRETATION: Our study documents a variability in prevalence of disease phenotypes and disparities in therapeutic choices and outcomes across geographical areas and wealth status of countries. The greater disease burden in lower-resource settings highlights the need for public health efforts aimed at improving equity in access to effective treatments and care for juvenile idiopathic arthritis