BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints affecting 1% of the world population. It has major impact on patients through disability and associated comorbidities. Current treatment strategies have considerably improved the prognosis, but recent innovations (especially biologic drugs and the new class of so-called "JAK/STAT inhibitors") have important safety issues and are very costly. Glucocorticoids (GCs) are highly effective in RA, and could reduce the need for expensive treatment with biologic agents. However, despite more than 65 years of clinical experience, there is a lack of studies large enough to adequately document the benefit/harm balance. The result is inappropriate treatment strategies, i.e. both under-use and over-use of GCs, and consequently suboptimal treatment of RA.

METHODS: The GLORIA study is a pragmatic multicentre, 2-year, randomised, double-blind, clinical trial to assess the safety and effectiveness of a daily dose of 5 mg prednisolone or matching placebo added to standard of care in elderly patients with RA. Eligible participants are diagnosed with RA, have inadequate disease control (disease activity score, DAS28 ≥ 2.6), and are ≥ 65 years. The primary outcome measures are the time-averaged mean value of the DAS28 and the occurrence of serious adverse events or adverse events of special interest. During the trial, change in antirheumatic therapy is permitted as clinically indicated, except for GCs. Cost-effectiveness and cost-utility are secondary outcomes. The main challenge is the interpretation of the trial result with two primary endpoints and the pragmatic trial design that allows co-interventions. Another challenge is the definition of safety and the relative lack of power to detect differences between treatment groups. We have chosen to define safety as the number of patients experiencing at least one serious adverse event. We also specify a decision tree to guide our conclusion on the balance of benefit and harm, and our methodology to combat potential confounding caused by co-interventions.

DISCUSSION: Pragmatic trials minimise impact on daily practice and maximise clinical relevance of the results, but analysis and interpretation of the results is challenging. We expect that the results of this trial are of importance for all rheumatologists who treat elderly patients with RA.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT02585258 . Registered on 20 October 2015.

Importance: There is no consensus on which domains should be measured or which instruments should be used in clinical trials for psoriasis therapies.

Objective: To achieve international consensus among psoriasis stakeholders on a core set of domains that should be measured in all psoriasis clinical trials.

Design, Setting, and Participants: Literature review, pre-Delphi survey exercises, nominal group discussions, and audience voting at 4 stakeholder meetings were used to develop candidate domains for 2 rounds of a Delphi survey. Stakeholders were patients or advocates of patients with psoriasis and health care professionals (HCPs) with expertise in psoriasis, including physicians, scientists, advocacy organization representatives, and regulators. Delphi surveys were conducted electronically from October through December 2015 and between September and October 2016. Stakeholder discussions with audience response voting were conducted at live meetings in the United States, Canada, and Italy from January 2013 to December 2016 to refine and ratify the core set of domains.

Main Outcomes and Measures: Two rounds of an electronic Delphi survey were used to determine consensus. A domain was considered "core" (ie, should be measured in all trials) if a threshold consensus of at least 70% was met in both patient and HCP groups. Domains meeting consensus in only 1 group were considered to be important but were not required to be measured in all trials ("middle ring"). These domains were included for rerating in round 2. Domains that did not meet consensus in either of the groups ("outer ring") were considered to be of uncertain importance and were placed in the research agenda.

Results: In round 1 of the Delphi survey, 107 HCPs and 14 patients participated. Most HCPs (72 [67%]) were dermatologists between 46 and 64 years old (71 [66%]), white (78 [73%]), and male (75 [70%]) from North America (60 [57%]) and Europe (34 [32%]).There were 10 pharmaceutical industry clinical or health economic scientists, 3 advocacy organization representatives, 2 regulatory agency representatives, and 5 "other." In the second round, 77 HCPs and 15 patients participated. Of the 20 candidate domains, the following 6 met consensus as core domains: skin manifestations, psoriasis and psoriatic arthritis symptoms, health-related quality of life, investigator global assessment, patient global assessment, and treatment satisfaction. Secondary skin manifestations as well as nail, inverse, genital, and guttate psoriasis were classified as important but not mandatory. Psoriatic arthritis signs, work productivity or participation, economic impact (direct and indirect cost), and cardiovascular disease comprised the research agenda.

Conclusions and Relevance: This iterative Delphi process yielded international consensus among professional and patient stakeholders on 6 domains that should be measured in all clinical trials for psoriasis. Future International Dermatology Outcome Measures group efforts will focus on development of a core outcome measurement set for psoriasis trials.

INTRODUCTION: Chronic inflammatory diseases (CIDs) are frequently treated with biological medications, specifically tumour necrosis factor inhibitors (TNFi)). These medications inhibit the pro-inflammatory molecule TNF alpha, which has been strongly implicated in the aetiology of these diseases. Up to one-third of patients do not, however, respond to biologics, and lifestyle factors are assumed to affect treatment outcomes. Little is known about the effects of dietary lifestyle as a prognostic factor that may enable personalised medicine. The primary outcome of this multidisciplinary collaborative study will be to identify dietary lifestyle factors that support optimal treatment outcomes.

METHODS AND ANALYSIS: This prospective cohort study will enrol 320 patients with CID who are prescribed a TNFi between June 2017 and March 2019. Included among the patients with CID will be patients with inflammatory bowel disease (Crohn's disease and ulcerative colitis), rheumatic disorders (rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis), inflammatory skin diseases (psoriasis, hidradenitis suppurativa) and non-infectious uveitis. At baseline (pretreatment), patient characteristics will be assessed using patient-reported outcome measures, clinical assessments of disease activity, quality of life and lifestyle, in addition to registry data on comorbidity and concomitant medication(s). In accordance with current Danish standards, follow-up will be conducted 14-16 weeks after treatment initiation. For each disease, evaluation of successful treatment response will be based on established primary and secondary endpoints, including disease-specific core outcome sets. The major outcome of the analyses will be to detect variability in treatment effectiveness between patients with different lifestyle characteristics.

ETHICS AND DISSEMINATION: The principle goal of this project is to improve the quality of life of patients suffering from CID by providing evidence to support dietary and other lifestyle recommendations that may improve clinical outcomes. The study is approved by the Ethics Committee (S-20160124) and the Danish Data Protecting Agency (2008-58-035). Study findings will be disseminated through peer-reviewed journals, patient associations and presentations at international conferences.

TRIAL REGISTRATION NUMBER: NCT03173144; Pre-results.

Patients with skin disorders are considered at a higher risk of depression and anxiety than the background population. Patients with hidradenitis suppurativa (HS) may be particularly affected. We explored the association between HS and depression, anxiety, and completed suicides in the Danish national registries, expanding to include data on suicidal behavior, using both a cross-sectional and a cohort study design. Both designs included 7,732 patients with HS and a background population of 4,354,137. The cohort study revealed that HS patients had an increased risk of completed suicide after adjustment for confounding factors (11 per 7,732 vs. 2,904 per 4,354,137) (hazard ratio [95% confidence interval] = 2.42 [1.07-5.45]; P = 0.0334) and an increased risk of antidepressant drug use (1.30 [1.17-1.45]; P < 0.0001). In contrast to previous studies, the cross-sectional baseline data revealed nonsignificant association with depression (odds ratio [95% confidence interval] = 1.13; 0.87-1.47]; P = 0.36 and hospitalization due to depression (1.32 [0.94-1.85]; P = 0.1083). To the best of our knowledge, no previous studies have reported on the increased risk of completed suicide among HS patients. The increased risk of completed suicide is not solely explained by lifestyle and demographic differences and the results highlight the profound impact HS has on the lives of patients with this often devastating disease.

Newly arrived migrants to the EU/EEA (arrival within the past five years), as well as other migrant groups in the region, might be under-immunised and lack documentation of previous vaccinations, putting them at increased risk of vaccine-preventable diseases circulating in Europe. We therefore performed a systematic review conforming to PRISMA guidelines (PROSPERO CRD42016045798) to explore: (i) interventions that improve vaccine uptake among migrants; and (ii) cost-effectiveness of vaccination strategies among this population. We searched MEDLINE, Embase, CINAHL, and Cochrane Database of Systematic Reviews (CDSR) between 1 January 2006 to 18 June 2018. We included three primary intervention studies performed in the EU/EEA or high-income countries and one cost effectiveness study relevant to vaccinations in migrants. Intervention studies showed small but promising impact only on vaccine uptake with social mobilization/community outreach, planned vaccination programs and education campaigns. Targeting migrants for catch-up vaccination is cost effective for presumptive vaccination for diphtheria, tetanus, and polio, and there was no evidence of benefit of carrying out pre-vaccination serological testing. The cost-effectiveness is sensitive to the seroprevalence and adherence to vaccinations of the migrant. We conclude that scarce but direct EU/EEA data suggest social mobilization, vaccine programs, and education campaigns are promising strategies for migrants, but more research is needed. Research should also study cost effectiveness of strategies. Vaccination of migrants should continue to be a public heath priority in EU/EEA.

OBJECTIVE: Parental and child co-sleeping has been suggested as a risk factor for short sleep duration and poor sleep quality that may lead to overweight. We examined if joining parent's bed during night was associated with child overweight.

METHODS: Cross-sectional data from the 'Healthy Start' study including 635 2- to 6-year-old Danish children, who were all considered obesity prone. Of these, 496 children had complete information on BMI and whether the child joined parents' bed during night and if so, how frequently. International cut-offs for overweight according to age and gender were applied, and logistic regression was used to estimate odds ratio (OR) and 95% Confidence Intervals (CI). Analyses were adjusted for the child's age and gender, overall family stress, parental educational level, and parental BMI.

RESULTS: Children who did not join their parent's bed were more likely to be overweight compared to children who did (OR 1.75 (95% CI 0.99-3.10)). Children who rarely joined their parents' bed had OR 2.74 of being overweight (95% CI 1.01-7.44) compared to children who joined every night.

CONCLUSION: Children who rarely joined parents' bed during night were almost three times more likely to be overweight than those who joined every night.

BACKGROUND: Exposure to road traffic noise was associated with increased risk of estrogen receptor (ER)-negative (ER-) breast cancer in a previous cohort study, but not with overall or ER-positive (ER+) breast cancer, or breast cancer prognosis. We examined the association between long-term exposure to road traffic noise and incidence of breast cancer, overall and by ER and progesterone receptor (PR) status.

METHODS: We used the data from a nationwide Danish Nurse Cohort on 22,466 female nurses (age > 44 years) who at recruitment in 1993 or 1999 reported information on breast cancer risk factors. We obtained data on the incidence of breast cancer from the Danish Cancer Registry, and on breast cancer subtypes by ER and PR status from the Danish Breast Cancer Cooperative Group, up to 31 December 2012. Road traffic noise levels at the nurses' residences were estimated by the Nord2000 method between 1970 and 2013 as annual means of a weighted 24 h average (Lden) at the most exposed facade. We used time-varying Cox regression to analyze the associations between the 24-year, 10-year, and 1-year mean of Lden and breast cancer, separately for total breast cancer and by ER and PR status.

RESULTS: Of the 22,466 women, 1193 developed breast cancer in total during 353,775 person-years of follow up, of whom 611 had complete information on ER and PR status. For each 10 dB increase in 24-year mean noise levels at their residence, we found a statistically significant 10% (hazard ratio and 95% confidence interval 1.10; 1.00-1.20) increase in total breast cancer incidence and a 17% (1.17; 1.02-1.33) increase in analyses based on 611 breast cancer cases with complete ER and PR information. We found positive, statistically significant association between noise levels and ER+ (1.23; 1.06-1.43, N = 494) but not ER- (0.93; 0.70-1.25, N = 117) breast cancers, and a stronger association between noise levels and PR+ (1.21; 1.02-1.42, N = 393) than between noise levels and PR- (1.10; 0.89-1.37, N = 218) breast cancers. Association between noise and ER+ breast cancer was statistically significantly stronger in nurses working night shifts (3.36; 1.48-7.63) than in those not working at night (1.21; 1.02-1.43) (p value for interaction = 0.05).

CONCLUSION: Long-term exposure to road traffic noise may increase risk of ER+ breast cancer.

In women, a large hip circumference (HC) related to lower hip fracture risk, independent of age and regardless if HC was measured long before or closer to the fracture. In older women, body mass index (BMI) explained the protection.

INTRODUCTION: In postmenopausal women, HC has been suggested to inversely associate with hip fracture while this has not been investigated in middle-aged women. We examined the association between HC, measured at two different time points, and hip fracture in a Swedish female population-based sample monitored for incident hip fractures over many years.

METHODS: Baseline HC, measured in 1968 or 1974 (n = 1451, mean age 47.6 years), or the HC measures that were the most proximal before event or censoring (n = 1325, mean age 71.7 years), were used to assess the effects of HC on hip fracture risk in women participating in the Prospective Population Study of Women in Gothenburg. HC was parameterized as quintiles with the lowest quintile (Q1) as reference. Incident hip fractures over 45 years of follow-up (n = 257) were identified through hospital registers.

RESULTS: Higher quintiles of HC at both baseline and proximal to event were inversely associated with hip fracture risk in age-adjusted models, but only baseline HC predicted hip fractures independently of BMI and other covariates (HR (95% CI) Q2, 0.85 (0.56-1.27); Q3, 0.59 (0.36-0.96); Q4, 0.57 (0.34-0.96); Q5, 0.58 (0.31-1.10)).

CONCLUSIONS: A large HC is protective against hip fracture in midlife and in advanced age, but the association between proximal HC and hip fracture was explained by concurrent BMI suggesting that padding was not the main mechanism for the association. The independent protection seen in middle-aged women points to other mechanisms influencing bone strength.

Objective: To assess the efficacy and safety of treatment modalities for major organ involvement of Behçet's syndrome (BS), in order to inform the update of the EULAR recommendations for the management of BS.

Methods: A systematic literature review of all randomized controlled trials, controlled clinical trials, or open label trials assessing eye, vascular, nervous system or gastrointestinal system involvement of BS was performed. If controlled trials were not available for answering a specific research question, uncontrolled studies or case series were also included.

Results: We reviewed the titles and abstracts of 3927 references and 161 studies met our inclusion criteria. There were only nine randomized controlled trials. Observational studies with IFN-α and monoclonal anti-TNF antibodies showed beneficial results for refractory uveitis. Meta-analysis of case-control studies showed that immunosuppressives decreased the recurrence rate of deep vein thrombosis significantly whereas anticoagulants did not. CYC and high dose glucocorticoids decreased mortality in pulmonary arterial aneurysms and postoperative complications in peripheral artery aneurysms. Beneficial results for gastrointestinal involvement were obtained with 5-ASA derivatives and AZA as first line treatment and with thalidomide and/or monoclonal anti-TNF antibodies in refractory cases. Observational studies for nervous system involvement showed improved outcome with immunosuppressives and glucocorticoids. Meta-analysis of case-control studies showed an increased risk of developing nervous system involvement with ciclosporin-A.

Conclusion: The majority of studies related to major organ involvement that informed the updated EULAR recommendations for the management of BS were observational studies.