Usability and Utility of a Mobile App to Deliver Health-Related Content to an Older Adult Population: Pilot Noncontrolled Quasi-Experimental Study.

BACKGROUND: Digital patient-centered interventions may be important tools for improving and promoting social interaction, health, and well-being among older adults. In this regard, we developed a mobile app called DigiAdherence for an older adult population, which consisted of easy-to-access short videos and messages, to improve health-related knowledge among them and prevent common health conditions, such as falls, polypharmacy, treatment adherence, nutritional problems, and physical inactivity. OBJECTIVE: This study aimed to assess the usability and utility of the DigiAdherence app among Portuguese older adults 65 years or older. METHODS: In this pilot noncontrolled quasi-experimental study, older adults who were patients at the primary health care center in Portimão, Portugal, and owned a smartphone or tablet were recruited. Participants were assessed at baseline, given access to the DigiAdherence app for 1 month, and assessed again immediately after 30 days (first assessment) and 60 days after stopping the use of the app (second assessment). App usability and utility (primary outcomes) were analyzed in the first follow-up assessment using a structured questionnaire with 8 items. In the second follow-up assessment, our focus was on knowledge acquired through the app. Secondary outcomes such as treatment adherence and health-related quality of life were also assessed. RESULTS: The study included 26 older adults. Most participants rated the different functionalities of the app positively and perceived the app as useful, attractive, and user-friendly (median score of 6 on a 7-point Likert scale). In addition, after follow-up, participants reported having a sense of security and greater knowledge in preventing falls (16/24, 67%) and managing therapies and polypharmacy (16/26, 62%). CONCLUSIONS: The DigiAdherence mobile app was useful and highly accepted by older adults, who developed more confidence regarding health-related knowledge. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/29675.

Determinants of health-related quality of life and global functioning and health in axSpA, pSpA, and PsA: results from the ASAS-PerSpA study.

OBJECTIVES: We aim to identify determinants of health-related quality of life (HRQoL) and global functioning and health (GH) in axial spondyloarthritis (axSpA), peripheral spondyloarthritis (pSpA), and psoriatic arthritis (PsA). METHODS: ASAS-perSpA study data were analyzed. Models for the three patient groups were performed separately to explore factors associated with HRQoL and GH, assessed by EQ-5D and ASAS-HI, respectively. RESULTS: The analyses included 4185 patients: 2719 with axSpA, 433 with pSpA, and 1033 with PsA.In axSpA, disease activity (DA) (ß=-0.061), physical function (ß=-0.041), female sex (ß=-0.019), and fibromyalgia (ß=-0.068) were associated with worse HRQoL; age (ß = 0.001) and university education (ß = 0.014) with better HRQoL. In pSpA, DA (ß=-0.04) and physical function (ß=-0.054) were associated with worse HRQoL. In PsA, DA (ß=-0.045), physical function (ß=-0.053), axial disease (ß=-0.041), and female sex (ß=-0.028) were associated with worse HRQoL.In axSpA, DA (ß = 0.889), physical function (ß = 0.887), peripheral disease (ß = 0.564), female sex (ß = 0.812) and fibromyalgia (ß = 1.639) were associated with worse GH; age (ß=-0.013) and university education (ß=-0.274) with better GH. In pSpA, physical function (ß = 1.142), and female sex (ß = 1.060) were associated with worse GH; university education (ß=-0.611) with better GH. In PsA, DA (ß = 0.703), physical function (ß = 1.025), axial involvement (ß = 0.659), female sex (ß = 0.924), and fibromyalgia (ß = 1.387) were associated with worse GH; age (ß=-0.024) and university education (ß=-0.856) with better GH. CONCLUSIONS: DA and physical function are major HRQoL and GH determinants across spondyloarthritis types, and clinical characteristics and sociodemographic factors play an important role, highlighting the importance of a holistic approach for individual patients.

Engaging European society at the forefront of cancer research and care: How discussions at the 5th Gago Conference on European Science policy led to the Heidelberg Manifesto

European cancer research stakeholders met in October 2022 in Heidelberg, Germany, at the 5th Gago conference on European Cancer Policy, to discuss the current cancer research and cancer care policy landscape in Europe. Meeting participants highlighted gaps in the existing European programmes focusing on cancer research, including Europe's Beating Cancer Plan (EBCP), the Mission on Cancer (MoC), Understanding Cancer (UNCAN.eu), and the joint action CRANE, and put forward the next priorities, in the form of the Heidelberg Manifesto for cancer research. This meeting report presents all discussions that shed light on how infrastructures can be effectively shaped for translational, prevention, clinical and outcomes cancer research, with a focus on implementation and sustainability and while engaging patients and the public. In addition, we summarize recommendations on how to introduce frameworks for the digitalization of European cancer research. Finally, we discuss what structures, commitment, and resources are needed to establish a collaborative cancer research environment in Europe to achieve the scale required for innovation.

Prevalence of and factors associated with unmanageable pain levels in people with knee or hip osteoarthritis: a cross-sectional population-based study.

BACKGROUND: Pain due to knee and / or hip osteoarthritis (HKOA) is the most common symptom for seeking healthcare. Pain interferes on daily activities, social and occupational participation in people with HKOA. The goal of this study is to estimate the prevalence of unmanageable pain levels (UPL) among people with HKOA), characterize this population and identify factors associated with UPL, and compare therapeutic strategies used by people with UPL versus manageable pain levels (MPL). METHODS: We analysed data from the EpiReumaPt study (n = 10,661), that included a representative sample of the Portuguese population. Among these, 1081 participants had a validated diagnosis of HKOA by a rheumatologist.. Sociodemographic, lifestyle and health-related data were collected in a structured interview. Pain intensity (NPRS) data were collected in a medical appointment. Painmedication (last month), physiotherapy and surgery were considered as therapies for pain management. UPL was defined as a mean pain intensity in the previous week of ≥5 points on 11-point numeric pain rating scale. The factors associated with UPL were analyzed with logistic regression (p < 0.05, 95%CI). The effect of unmanageable pain levels was assessed by the HOOS/KOOS activities of daily living and quality of life subscales. Symptoms of anxiety and depression were assessed by the Hospital Anxiety and Depression Scale (HADS). Analysis was completed with linear and logistic regression. All analysis were weighted. RESULTS: The estimated prevalence of UPL among people with HKOA was 68.8%. UPL was associated with being female (odds ratio (OR) = 2.36, p < 0.001), being overweight (OR = 1.84, p = 0.035) or obese (OR = 2.26, p = 0.006), and having multimorbidity (OR = 2.08, p = 0.002). People with UPL reported worse performance in activities of daily living and lower quality of life (ß = - 21.28, p < 0.001 and ß = - 21.19, p < 0.001, respectively) than people with MPL. People with UPL consumed more NSAIDs (22.0%, p = 0.003), opioids (4.8%, p = 0.008), paracetamol (2.7%, p = 0.033), and overall analgesics (7.3%, p = 0.013) than people with MPL. A higher proportion of people with UPL underwent physiotherapy (17.5%, p = 0.002) than people with MPL. CONCLUSION: Two-thirds of people with HKOA in Portugal have poor management of their pain levels. Clinical and lifestyle factors, that are highly presented in individuals with HKOA, are associated with unmanageable pain. Our results highlighting the need for further research and implementation of effective interventions to improve pain, function and quality of life in people with HKOA.

A Video-Based Mobile App as a Health Literacy Tool for Older Adults Living at Home: Protocol for a Utility Study.

BACKGROUND: People aged ≥65 years are more likely to have health problems related to aging, polypharmacy, and low treatment adherence. Moreover, health literacy levels decrease with increasing age. OBJECTIVE: The aim of this study is to assess an app's utility in promoting health-related knowledge in people aged ≥65 years. METHODS: We developed a simple, intuitive, and video-based app (DigiAdherence) that presents a recipe, nutritional counseling, and content on physical activity, cognitive exercise, motivation to adhere to treatment, fall prevention, and health literacy. A convenience sample of 25 older adults attending the Personalized Health Care Unit of Portimão or the Family Health Unit of Portas do Arade (ACeS Algarve II - Barlavento, ARS Algarve, Portugal) will be recruited. Subjects must be aged ≥65 years, own a smartphone or tablet, be willing to participate, and consent to participate. Those who do not know how to use or do not have a smartphone/tablet will be excluded. Likewise, people with major cognitive or physical impairment as well as those living in a long-term care center will not be included in this study. Participants will have access to the app for 4 weeks and will be evaluated at 3 different timepoints (V0, before they start using the app; V1, after using it for 30 days; and V2, 60 days after stopping using it). After using the app for 30 days, using a 7-point Likert scale, participants will be asked to score the mobile tool's utility in encouraging them to take their medications correctly, improving quality of life, increasing their health-related knowledge, and preventing falls. They will also be asked to assess the app's ease of use and visual esthetics, their motivation to use the app, and their satisfaction with the app. Subjects will be assessed in a clinical interview with a semistructured questionnaire, including questions regarding user experience, satisfaction, the utility of the app, quality of life (EQ-5D-3L instrument), and treatment adherence (Morisky scale). The proportion of participants who considered the app useful for their health at V1 and V2 will be analyzed. Regarding quality of life and treatment adherence perceptions, comparisons will be made between V0 and V1, using the t test for dependent samples. The same comparisons will be made between V0 and V2. RESULTS: This study was funded in December 2019 and authorized by the Executive Board of ACeS Algarve II - Barlavento and by the Ethics Committee of NOVA Medical School (99/2019/CEFCM, June 2020). This protocol was also approved by the Ethics Committee for Health (16/2020, September 2020) and the Executive Board (December 2020) of the Regional Health Administration of the Algarve, IP (Instituto Público). Recruitment was completed in June 2021. CONCLUSIONS: Since the next generation of older adults may have higher digital literacy, information and communication technologies could potentially be used to deliver health-related content to improve lifestyles among older adults. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/29675.

Protein intake, physical activity and grip strength in European and North American community-dwelling older adults: a pooled analysis of individual participant data from four longitudinal ageing cohorts.

INTRODUCTION: Higher dietary protein, alone or in combination with physical activity (PA), may slow the loss of age-related muscle strength in older adults. We investigated the longitudinal relationship between protein intake and grip strength, and the interaction between protein intake and PA, using four longitudinal ageing cohorts. METHODS: Individual participant data from 5584 older adults (52% women; median: 75, IQR: 71.6, 79.0 years) with up to 8.5 years (mean: 4.9, SD: 2.3 years) of follow-up from the Health ABC, NuAge, LASA and Newcastle 85+ cohorts were pooled. Baseline protein intake was assessed with food frequency questionnaires and 24h recalls and categorized into <0.8, 0.8-<1.0, 1.0-<1.2 and ≥1.2 g/kg adjusted body weight (aBW)/d. The prospective association between protein intake, its interaction with PA, and grip strength (sex- and cohort-specific) was determined using joint models (hierarchical linear mixed effects and a link function for Cox proportional hazards models). RESULTS: Grip strength declined on average by 0.018 SD (95%CI: -0.026, -0.006) every year. No associations were found between protein intake, measured at baseline, and grip strength, measured prospectively, or rate of decline of grip strength in models adjusted for sociodemographic, anthropometric, lifestyle and health variables (e.g., protein intake ≥1.2 vs <0.8 g/kg aBW/d: ß= -0.003, 95%CI: -0.014,0.005 SD per year). There also was no evidence of an interaction between protein intake and PA. CONCLUSIONS: We failed to find evidence in this study to support the hypothesis that higher protein intake, alone or in combination with higher PA, slowed the rate of grip strength decline in older adults.

Using Patient-Reported Outcome Measures to Evaluate Care for Patients With Inflammatory Chronic Rheumatic Disease.

OBJECTIVES: Few countries integrate patient-reported outcome measures (PROMs) in routine performance assessment and those that do focus on elective surgery. This study addresses the challenges of using PROMs to evaluate care in chronic conditions. We set out a modeling strategy to assess the extent to which changes over time in self-reported health status by patients with inflammatory chronic rheumatic disease are related to their biological drug therapy and rheumatology center primarily responsible for their care. METHODS: Using data from the Portuguese Register of Rheumatic Diseases, we assess health status using the Health Assessment Questionnaire-Disability Index for rheumatic patients receiving biological drugs between 2000 and 2017. We specify a fixed-effects model using the least squares dummy variables estimator. RESULTS: Patients receiving infliximab or rituximab report lower health status than those on etanercept (the most common therapy) and patients in 4 of the 26 rheumatology centers report higher health status than those at other centers. CONCLUSIONS: PROMs can be used for those with chronic conditions to provide the patient's perspective about the impact on their health status of the choice of drug therapy and care provider. Care for chronic patients might be improved if healthcare organizations monitor PROMs and engage in performance assessment initiatives on a routine basis.

Spotlight on latent tuberculosis infection screening for juvenile idiopathic arthritis in two countries, comparing high and low risk patients

Abstract Background: Rheumatic diseases are associated with an increase in overall risks of tuberculosis (TB). The aim of this study was to evaluate the frequency of TB and the frequency of latent TB infection (LTBI), in clinical practice, for juvenile idiopathic arthritis (JIA) patients from high and low risk of TB incidence endemic countries. Methods: This is an international, multicenter, cross-sectional, observational study of data collection from Brazil and Registry of Portugal at REUMA.PT. The inclusion criteria were patients with Juvenile Idiopathic Arthritis (JIA) with age ≤ 18 years who underwent screening for Mycobacterium tuberculosis infection [tuberculin skin test (TST) and/or interferon gamma release assay (IGRA)]. Chest X-rays and history of exposure to TB were also assessed. Results: 292 JIA patients were included; mean age 14.3 years, mean disease duration 7.5 years, 194 patients (66.4%) performed only TST, 14 (4.8%) only IGRA and 84 (28.8%) both. The frequency of LTBI (10.6%) and TB was similar between the two countries. The reasons for TB screening were different; in Brazil it was performed more often at JIA onset while in Portugal it was performed when starting Disease Modified Anti-Rheumatic Drugs (DMARD) treatment (p < 0.001). Isoniazid therapy was prescribed in 40 (13.7%) patients (31 with LTBI and 9 with epidemiologic risks and/or due to contact with sick people). Only three patients (1%) developed active TB. Conclusion: We found nearly 10% of patients with LTBI, a small percentage of patients with treatment due to epide-miologic risks and only 1% with active TB. Distinct reasons and screening methods for LTBI were observed between the two countries.

Validation of GWAS-Identified Variants for Anti-TNF Drug Response in Rheumatoid Arthritis: A Meta-Analysis of Two Large Cohorts.

We aimed to validate the association of 28 GWAS-identified genetic variants for response to TNF inhibitors (TNFi) in a discovery cohort of 1361 rheumatoid arthritis (RA) patients monitored in routine care and ascertained through the REPAIR consortium and DANBIO registry. We genotyped selected markers and evaluated their association with response to TNFi after 6 months of treatment according to the change in disease activity score 28 (ΔDAS28). Next, we confirmed the most interesting results through meta-analysis of our data with those from the DREAM cohort that included 706 RA patients treated with TNFi. The meta-analysis of the discovery cohort and DREAM registry including 2067 RA patients revealed an overall association of the LINC02549rs7767069 SNP with a lower improvement in DAS28 that remained significant after correction for multiple testing (per-allele ORMeta=0.83, PMeta=0.000077; PHet=0.61). In addition, we found that each copy of the LRRC55rs717117G allele was significantly associated with lower improvement in DAS28 in rheumatoid factor (RF)-positive patients (per-allele ORMeta=0.67, P=0.00058; PHet=0.06) whereas an opposite but not significant effect was detected in RF-negative subjects (per-allele ORMeta=1.38, P=0.10; PHet=0.45; PInteraction=0.00028). Interestingly, although the identified associations did not survive multiple testing correction, the meta-analysis also showed overall and RF-specific associations for the MAFBrs6071980 and CNTN5rs1813443 SNPs with decreased changes in DAS28 (per-allele ORMeta_rs6071980 = 0.85, P=0.0059; PHet=0.63 and ORMeta_rs1813443_RF+=0.81, P=0.0059; PHet=0.69 and ORMeta_rs1813443_RF-=1.00, P=0.99; PHet=0.12; PInteraction=0.032). Mechanistically, we found that subjects carrying the LINC02549rs7767069T allele had significantly increased numbers of CD45RO+CD45RA+ T cells (P=0.000025) whereas carriers of the LINC02549rs7767069T/T genotype showed significantly increased levels of soluble scavengers CD5 and CD6 in serum (P=0.00037 and P=0.00041). In addition, carriers of the LRRC55rs717117G allele showed decreased production of IL6 after stimulation of PBMCs with B burgdorferi and E coli bacteria (P=0.00046 and P=0.00044), which suggested a reduced IL6-mediated anti-inflammatory effect of this marker to worsen the response to TNFi. In conclusion, this study confirmed the influence of the LINC02549 and LRRC55 loci to determine the response to TNFi in RA patients and suggested a weak effect of the MAFB and CNTN5 loci that need to be further investigated.

Low protein intake, physical activity, and physical function in European and North American community-dwelling older adults: a pooled analysis of four longitudinal aging cohorts.

BACKGROUND: Dietary protein may slow the decline in muscle mass and function with aging, making it a sensible candidate to prevent or modulate disability progression. At present, studies providing reliable estimates of the association between protein intake and physical function, and its interaction with physical activity (PA), in community-dwelling older adults are lacking. OBJECTIVES: We investigated the longitudinal relation between protein intake and physical function, and the interaction with PA. METHODS: We undertook a pooled analysis of individual participant data from cohorts in the PROMISS (PRevention Of Malnutrition In Senior Subjects in the European Union) consortium (the Health Aging and Body Composition Study, Quebec Longitudinal Study on Nutrition and Successful Aging, Longitudinal Aging Study Amsterdam, and Newcastle 85+) in which 5725 community-dwelling older adults were followed up to 8.5 y. The relation between protein intake and walking speed was determined using joint models (linear mixed-effects and Cox proportional hazards models) and the relation with mobility limitation was investigated using multistate models. RESULTS: Higher protein intake was modestly protective of decline in walking speed in a dose-dependent manner [e.g., protein intake ≥1.2 compared with 0.8 g/kg adjusted body weight (aBW)/d: ß = 0.024, 95% CI: 0.009, 0.032 SD/y], with no clear indication of interaction with PA. Participants with protein intake ≥0.8 g/kg aBW/d had also a lower likelihood of incident mobility limitation, which was observed for each level of PA. This association seemed to be dose-dependent for difficulty walking but not for difficulty climbing stairs. No associations between protein intake and other mobility limitations transitions were observed. CONCLUSIONS: Higher daily protein intake can reduce physical function decline not only in older adults with protein intake below the current RDA of 0.8 g/kg BW/d, but also in those with a protein intake that is already considered sufficient. This dose-dependent association was observed for each level of PA, suggesting no clear synergistic association between protein intake and PA in relation to physical function.

NFKB2 polymorphisms associate with the risk of developing rheumatoid arthritis and response to TNF inhibitors: Results from the REPAIR consortium.

This study sought to evaluate the association of 28 single nucleotide polymorphisms (SNPs) within NFKB and inflammasome pathway genes with the risk of rheumatoid arthritis (RA) and response to TNF inhibitors (TNFi). We conducted a case-control study in a European population of 1194 RA patients and 1328 healthy controls. The association of potentially interesting markers was validated with data from the DANBIO (695 RA patients and 978 healthy controls) and DREAM (882 RA patients) registries. The meta-analysis of our data with those from the DANBIO registry confirmed that anti-citrullinated protein antibodies (ACPA)-positive subjects carrying the NFKB2rs11574851T allele had a significantly increased risk of developing RA (PMeta_ACPA + = 0.0006) whereas no significant effect was found in ACPA-negative individuals (PMeta_ACPA- = 0.35). An ACPA-stratified haplotype analysis including both cohorts (n = 4210) confirmed that ACPA-positive subjects carrying the NFKB2TT haplotype had an increased risk of RA (OR = 1.39, P = 0.0042) whereas no effect was found in ACPA-negative subjects (OR = 1.04, P = 0.82). The meta-analysis of our data with those from the DANBIO and DREAM registries also revealed a suggestive association of the NFKB2rs1056890 SNP with larger changes in DAS28 (OR = 1.18, P = 0.007). Functional experiments showed that peripheral blood mononuclear cells from carriers of the NFKB2rs1005044C allele (in LD with the rs1056890, r2 = 1.00) showed increased production of IL10 after stimulation with LPS (P = 0.0026). These results provide first evidence of a role of the NFKB2 locus in modulating the risk of RA in an ACPA-dependent manner and suggest its implication in determining the response to TNFi. Additional studies are now warranted to further validate these findings.

Prevalence of vitamin D deficiency and its predictors in the Portuguese population: a nationwide population-based study.

Vitamin D deficiency is prevalent worldwide, but its prevalence is unknown in adult Portuguese population. In Portugal, 66% of adults present Vitamin D insufficiency/deficiency. Winter, living in Azores, older age, and obesity were the most important risk factors. It highlights the need of strategies to prevent vitamin D deficiency in Portugal. OBJECTIVE: To estimate the prevalence and risk factors of vitamin D deficiency in the adult Portuguese population. METHODS: Adults (≥ 18 years old) from the EpiReumaPt Study (2011-2013) were included. Standardized questionnaires on socio-demographic and lifestyle features were obtained. Serum 25-hydroxyvitamin D [25(OH)D] concentrations were evaluated using ADVIA Centaur VitD competitive immunoassay (Siemens Healthineers) in 2015-2017 as 25 (OH)D Level 0: ≤ 10 ng/mL; Level 1: 11-19 ng/mL; Level 2: 20-29 ng/mL, and Level 3: ≥ 30 ng/mL. Weighted multinomial regression analysis was conducted to evaluate the association between socio-demographic and lifestyle variables and vitamin D status. RESULTS: Based on weighted analysis, the estimated prevalence of levels of 25(OH)D ≤ 10, < 20, and < 30 ng/mL was 21.2, 66.6, and 96.4%, respectively. The strongest independent predictors of serum 25 (OH)D ≤ 10 ng/mL were living in the Azores archipelagos (OR 9.39; 95%CI 1.27-69.6) and having the blood sample collection in winter (OR 18.53; 95%CI 7.83-43.87) or spring (11.55; 95%CI 5.18-25.74). Other significant predictors included older age (OR 5.65, 95%CI 2.08-15.35), obesity (OR 2.61; 95%CI 1.35-5.08), current smoking (OR 2.33; 95%CI 1.23-4.43), and female gender (OR 1.9, 95%CI 1.1-3.28). Conversely, physical exercise (OR 0.48, 95%CI 0.28-0.81) and occasional alcohol intake (OR 0.48, 95%CI 0.29-0.81) were associated with a lower risk of 25(OH)D ≤ 10 ng/mL. CONCLUSION: Vitamin D deficiency/insufficiency [25(OH)D < 20 ng/ml] is highly prevalent in Portugal, affecting > 60% of all Portuguese adults, with strong geographical and seasonal variation. This study highlights the need to critically assess the relevance of vitamin D deficiency as a public health problem and the urgent need for a wide and scientifically robust debate about the most appropriate interventions at the individual and societal levels.

GO-DACT: a phase 3b randomised, double-blind, placebo-controlled trial of GOlimumab plus methotrexate (MTX) versus placebo plus MTX in improving DACTylitis in MTX-naive patients with psoriatic arthritis.

OBJECTIVES: To assess the efficacy of golimumab in combination with methotrexate (MTX) versus MTX monotherapy in psoriatic arthritis (PsA) dactylitis. METHODS: Multicentre, investigator-initiated, randomised, double-blind, placebo-controlled, parallel-design phase 3b trial in 11 Portuguese rheumatology centres. Patients with PsA along with active dactylitis and naive to MTX and biologic disease-modifying antirheumatic drugs (bDMARDs) were randomly assigned to golimumab or placebo, both in combination with MTX. The primary endpoint was Dactylitis Severity Score (DSS) change from baseline to week 24. Key secondary endpoints included DSS and Leeds Dactylitis Index (LDI) response, and changes from baseline in the LDI and MRI dactylitis score. Analysis was by intention-to-treat for the primary endpoint. RESULTS: Twenty-one patients received golimumab plus MTX and 23 MTX monotherapy for 24 weeks. One patient from each arm discontinued. Patient inclusion was halted at 50% planned recruitment due to a favourable interim analysis. Median baseline DSS was 6 in both arms. By week 24, patients treated with golimumab plus MTX exhibited significantly greater improvements in DSS relative to MTX monotherapy (median change of 5 vs 2 points, respectively; p=0.026). In the golimumab plus MTX arm, significantly higher proportions of patients achieved at least 50% or 70% improvement in DSS and 20%, 50% or 70% improvement in LDI in comparison to MTX monotherapy. CONCLUSIONS: The combination of golimumab and MTX as first-line bDMARD therapy is superior to MTX monotherapy for the treatment of PsA dactylitis. TRIAL REGISTRATION NUMBER: NCT02065713.

Steroid hormone-related polymorphisms associate with the development of bone erosions in rheumatoid arthritis and help to predict disease progression: Results from the REPAIR consortium.

Here, we assessed whether 41 SNPs within steroid hormone genes associated with erosive disease. The most relevant finding was the rheumatoid factor (RF)-specific effect of the CYP1B1, CYP2C9, ESR2, FcγR3A, and SHBG SNPs to modulate the risk of bone erosions (P = 0.004, 0.0007, 0.0002, 0.013 and 0.015) that was confirmed through meta-analysis of our data with those from the DREAM registry (P = 0.000081, 0.0022, 0.00074, 0.0067 and 0.0087, respectively). Mechanistically, we also found a gender-specific correlation of the CYP2C9rs1799853T/T genotype with serum vitamin D3 levels (P = 0.00085) and a modest effect on IL1ß levels after stimulation of PBMCs or blood with LPS and PHA (P = 0.0057 and P = 0.0058). An overall haplotype analysis also showed an association of 3 ESR1 haplotypes with a reduced risk of erosive arthritis (P = 0.009, P = 0.002, and P = 0.002). Furthermore, we observed that the ESR2, ESR1 and FcγR3A SNPs influenced the immune response after stimulation of PBMCs or macrophages with LPS or Pam3Cys (P = 0.002, 0.0008, 0.0011 and 1.97•10-7). Finally, we found that a model built with steroid hormone-related SNPs significantly improved the prediction of erosive disease in seropositive patients (PRF+ = 2.46•10-8) whereas no prediction was detected in seronegative patients (PRF- = 0.36). Although the predictive ability of the model was substantially lower in the replication population (PRF+ = 0.014), we could confirm that CYP1B1 and CYP2C9 SNPs help to predict erosive disease in seropositive patients. These results are the first to suggest a RF-specific association of steroid hormone-related polymorphisms with erosive disease.

Association of response to TNF inhibitors in rheumatoid arthritis with quantitative trait loci for CD40 and CD39.

OBJECTIVES: We sought to investigate whether genetic effects on response to TNF inhibitors (TNFi) in rheumatoid arthritis (RA) could be localised by considering known genetic susceptibility loci for relevant traits and to evaluate the usefulness of these genetic loci for stratifying drug response. METHODS: We studied the relation of TNFi response, quantified by change in swollen joint counts ( Δ SJC) and erythrocyte sedimentation rate ( Δ ESR) with locus-specific scores constructed from genome-wide assocation study summary statistics in 2938 genotyped individuals: 37 scores for RA; scores for 19 immune cell traits; scores for expression or methylation of 93 genes with previously reported associations between transcript level and drug response. Multivariate associations were evaluated in penalised regression models by cross-validation. RESULTS: We detected a statistically significant association between Δ SJC and the RA score at the CD40 locus (p=0.0004) and an inverse association between Δ SJC and the score for expression of CD39 on CD4 T cells (p=0.00005). A previously reported association between CD39 expression on regulatory T cells and response to methotrexate was in the opposite direction. In stratified analysis by concomitant methotrexate treatment, the inverse association was stronger in the combination therapy group and dissipated in the TNFi monotherapy group. Overall, ability to predict TNFi response from genotypic scores was limited, with models explaining less than 1% of phenotypic variance. CONCLUSIONS: The association with the CD39 trait is difficult to interpret because patients with RA are often prescribed TNFi after failing to respond to methotrexate. The CD39 and CD40 pathways could be relevant for targeting drug therapy.

Polymorphisms at phase I-metabolizing enzyme and hormone receptor loci influence the response to anti-TNF therapy in rheumatoid arthritis patients.

The aim of this case-control study was to evaluate whether 47 single-nucleotide polymorphisms (SNPs) in steroid hormone-related genes are associated with the risk of RA and anti-TNF drug response. We conducted a case-control study in 3 European populations including 2936 RA patients and 2197 healthy controls. Of those, a total of 1985 RA patients were treated with anti-TNF blockers. The association of potentially interesting markers in the discovery population was validated through meta-analysis with data from DREAM and DANBIO registries. Although none of the selected variants had a relevant role in modulating RA risk, the meta-analysis of the linear regression data with those from the DREAM and DANBIO registries showed a significant correlation of the CYP3A4rs11773597 and CYP2C9rs1799853 variants with changes in DAS28 after the administration of anti-TNF drugs (P = 0.00074 and P = 0.006, respectively). An overall haplotype analysis also showed that the ESR2GGG haplotype significantly associated with a reduced chance of having poor response to anti-TNF drugs (P = 0.0009). Finally, a ROC curve analysis confirmed that a model built with eight steroid hormone-related variants significantly improved the ability to predict drug response compared with the reference model including demographic and clinical variables (AUC = 0.633 vs. AUC = 0.556; PLR_test = 1.52 × 10-6). These data together with those reporting that the CYP3A4 and ESR2 SNPs correlate with the expression of TRIM4 and ESR2 mRNAs in PBMCs (ranging from P = 1.98 × 10-6 to P = 2.0 × 10-35), and that the CYP2C9rs1799853 SNP modulates the efficiency of multiple drugs, suggest that steroid hormone-related genes may have a role in determining the response to anti-TNF drugs.KEY POINTS• Polymorphisms within the CYP3A4 and CYP2C9 loci correlate with changes in DAS28 after treatment with anti-TNF drugs.• A haplotype including eQTL SNPs within the ESR2 gene associates with better response to anti-TNF drugs.• A genetic model built with eight steroid hormone-related variants significantly improved the ability to predict drug response.

Psoriatic arthritis and ankylosing spondylitis impact on health-related quality of life and working life: a comparative population-based study.

INTRODUCTION: Psoriatic arthritis (PsA) and ankylosing spondylitis (AS) are chronic disorders that significantly impact patients' quality of life (QoL), health care systems and society. There is very little data on the epidemiology and the impact of PsA and AS in Portugal, so in this study we aim to: 1) estimate the prevalence of PsA and AS in the adult Portuguese population; 2) compare health-related quality of life (QoL) of PsA and AS with the one of other rheumatic and musculoskeletal diseases (RMD) and with subjects with no rheumatic diseases; 3) compare early retirement and productivity loss among PsA and AS with other RMD. METHODS: We used data from EpiReumaPt, a population-based survey, conducted from 2011 to 2013, in which 10661 subjects over 18 years old were screened for RMD. Spondyloarthritis (SpA) was defined by a positive expert opinion combined with the fulfillment of the assessment of spondyloarthritis international society (ASAS) criteria for axial and peripheral SpA. Estimates were computed as weighted proportions considering the study design. Logistic regressions were used to compare AS/PsA subjects with other RMD and the adult Portuguese population without rheumatic diseases. RESULTS: Prevalence rate of SpA was 1.6% (95% CI 1.2% to 2.1%). Subjects with AS or PsA had worse QoL, reflected by EQ5D score when compared with the adult Portuguese population without rheumatic diseases (ß=- 0.08; p=0.031). AS and PsA also had worst QoL when compared with participants with other RMD (ß=-0.22; p>0.001). AS and in comparison to patients with other RMD, PsA subjects retired early due to their illness (OR=4.95; 95% CI 1.54% to 15.93%). A significant proportion of patients with SpA (13.6%) referred absenteeism in the previous 12 months to the interview. CONCLUSIONS: AS and PsA were found to be associated with poor QoL and a high rate of disease-related early retirement, emphasizing the burden of such rheumatic conditions in Portugal.

Psychological distress in elderly people is associated with diet, wellbeing, health status, social support and physical functioning- a HUNT3 study.

BACKGROUND: The increasing proportion of people growing old, demands expanded knowledge of how people can experience successful aging. Having a good life while growing old is dependent on several factors such as nutrition, physical health, the ability to perform activities of daily living, lifestyle and psychological health. Furthermore, unhealthy food intake is found to be a modifiable risk factor for depression in elderly people. To promote elderly's health and wellbeing, the influence of nutrition, lifestyle, physical functioning, and social support on psychological distress needs exploring. Therefore, the purpose of this present study is to investigate the associations between psychological distress and diet patterns when adjusting for other life style behaviors, wellbeing, health status, physical functioning and social support in elderly people. METHODS: The present study is cross sectional, using data from wave three of the Nord-Trøndelag Health Study (2006-2008). Data include psychological distress measured by the Hospital Anxiety and Depression Scale (HADS), sociodemographic information, measurements of lifestyle behaviours (including diet patterns), wellbeing, health status, social support and physical functioning. RESULTS: The sample consisted of 11,621 participants, 65 years or older. Cluster analysis categorized the participants in two food clusters based on similarities in food consumption (healthy N = 9128, unhealthy N = 2493). Stepwise multivariable linear regression analyses revealed that lesser psychological distress in the elderly was dependent on gender, diet, smoking, better scores on health and wellbeing, social support and less problems performing instrumental activities of daily living. CONCLUSION: Knowledge about the influence of diet patterns in relation to psychological distress provide valuable insights into how society can promote healthy lifestyles to an ageing population, e.g. by increasing older people's food knowledge.

Sleep duration, lifestyles and chronic diseases: a cross-sectional population-based study.

BACKGROUND: Adequate sleep is essential for health. Both, short and long sleep durations are associated to worse quality of life and poor health outcomes. Portugal represents a specific population model, since according to European statistics it has high rates of chronic diseases like depression, hypertension, diabetes and stroke; and low quality of life as well as low index of physical activity, while in parallel it has some other good health indicators such as: low age-standardized mortality for both genders, nutrition in terms of energy and fruit consumption, smoking and alcohol, obesity and overweight prevalence. The aim of this study was to characterize health and chronic diseases, lifestyles and quality of life in subjects with short and long sleep duration. METHODS: A population-based cross-sectional evaluation of the third wave of follow-up of the EpiDoC Cohort was carried between 2015-2016. A sample of 5,436 adults ≥18 years, representative of the national population, self-reported their daily total sleep time. Associations between short sleep duration (SSD ≤5h), long sleep duration (LSD≥9h) and independent variables were determined. RESULTS: The prevalence for SSD was high (20.7%) and the LSD (5.9%) was low. Being older, with lower education, retired and unemployed were associated to SSD and LSD (p<0.01). Being obese was associated to SSD as well as hypertension, gastrointestinal disease and hypercholesterolemia (p<0.01). SSD and LSD, were associated with diabetes (p<0.01 and p=0.03) and depression (p<0.01 and p=0.02) respectively. Cardiovascular disease (p<0.01) was associated to LSD. Multimorbidity (p<0.01) was associated to SSD. Worse quality of life and bad physical function were associated to SSD and LSD, as well as being hospitalized in the previous 12 months (p<0.01). CONCLUSIONS: Socio-demographic, physical activity and chronic diseases were associated to reduction and extension of sleep duration. There was no association between rheumatic diseases and cancer with sleep duration, as found in other studies. This study emphasizes the burden of self-reported SSD for Portugal, its consequences to health and the need to increase sleep awareness campaigns enhancing the importance of sleep in health. Furthermore, it emphasizes that chronic diseases risks are dependent on multiple parameters which varying in different countries or regions, imply the need of regional studies and interventions.