Several genetic variants in Toll-like receptor (TLR) and nuclear factor (NF)-κB signalling pathways have been reported associated with responsiveness to tumour necrosis factor inhibitor (anti-TNF) treatment in rheumatoid arthritis (RA). The present study was undertaken to replicate these findings. In a retrospective case-case study including 1007 Danish anti-TNF-treated RA patients, we genotyped 7 previously reported associated single-nucleotide polymorphisms (SNPs) in these pathways. Furthermore, 5 SNPs previously reported by our group were genotyped in a subcohort (N=469). Primary analyses validated the IRAK3 rs11541076 variant as associated (odds ratio (OR)=1.33, 95% confidence interval (CI): 1.00-1.77, P-value=0.047) with a positive treatment response (EULAR (European League Against Rheumatism) good/moderate vs none response at 4±2 months), and found the NLRP3 rs461266 variant associated (OR=0.75, 95% CI: 0.60-0.94, P=0.014) with a negative treatment response. Meta-analyses combining data from previous studies suggested smaller effect sizes of associations between variant alleles of CHUK rs11591741, NFKBIB rs3136645 and rs9403 and a negative treatment response. In conclusion, this study validates rs11541076 in IRAK3, a negative regulator of TLR signalling, as a predictor of anti-TNF treatment response, and suggests true positive associations of previously reported SNPs within genes encoding activators/inhibitors of NF-κB (CHUK, MYD88, NFKBIB, and NLRP3).The Pharmacogenomics Journal advance online publication, 4 October 2016; doi:10.1038/tpj.2016.66.

The present study investigated the day-to-day reliability (quantified by the absolute and relative reliability) of nonlinear methods used to assess human locomotion dynamics. Twenty-four participants of whom twelve were diagnosed with knee osteoarthritis completed 5 min of treadmill walking at self-selected preferred speed on two separate days. Lower limb kinematics were recorded at 100 Hz and hip, knee, and ankle joint angles, three-dimensional (3D) sacrum marker displacement and stride time intervals were extracted for 170 consecutive strides. The largest Lyapunov exponent and correlation dimension were calculated for the joint angle and sacrum displacement data using three different state space reconstruction methods (group average, test-retest average, individual time delay and embedding dimension). Sample entropy and detrended fluctuation analysis (DFA) were applied to the stride time interval time series. Relative reliability was assessed using intraclass correlation coefficients and absolute reliability was determined using measurement error (ME). For both joint angles and sacrum displacement, there was a general pattern that the group average state space reconstruction method provided the highest relative reliability and lowest ME compared to the individual and test-retest average methods. The DFA exhibited good reliability, while the sample entropy showed poor reliability. The results comprise a reference material that can inspire and guide future studies of nonlinear gait dynamics.

Infants who are breastfed are introduced to a variety of flavours from the maternal milk, and thus the transition from maternal milk to complementary foods may be easier for these children. The aim of this study was to investigate if duration of exclusive breastfeeding was associated with pickiness or dietary intake of vegetables, fruit, starchy foods or sugar sweetened beverages among obesity prone normal weight children aged 2-6 years. This cohort study was based on data from the Healthy Start primary intervention study, the Danish Medical Birth registry and the Danish Health Visitor's Child Health Database. Infant feeding was registered by health nurses while home-visiting the mother and child up to four times within the first year. Information on eating behaviour and diet intake at age 2-6 years was obtained by parents. Crude and adjusted logistic and general linear regression models were used to investigate associations. A total of 236 children had complete information on all variables. Data showed lower odds of picky eating behaviour when exclusively breastfed until age 4-5 months compared to exclusively breastfed for 0-1 months (OR = 0.35, 95CI = 0.16;0.76, p = 0.008). In the crude analysis only, exclusively breastfed until age 6-10 months was associated with a higher daily intake of vegetables (p = 0.04). This study suggests that exclusive breastfeeding duration seems to influence pickiness and may contribute to facilitate the consumption of more vegetables in later childhood in obesity prone normal weight children.

INTRODUCTION: An unbalanced intestinal microbiota may mediate activation of the inflammatory pathways seen in psoriatic arthritis (PsA). A randomised, placebo-controlled trial of faecal microbiota transplantation (FMT) infused into the small intestine of patients with PsA with active peripheral disease who are non-responsive to methotrexate (MTX) treatment will be conducted. The objective is to explore clinical aspects associated with FMT performed in patients with PsA.

METHODS AND ANALYSIS: This trial is a randomised, two-centre stratified, double-blind (patient, care provider and outcome assessor), placebo-controlled, parallel-group study. Eighty patients will be included and randomised (1:1) to either placebo (saline) or FMT provided from an anonymous healthy donor. Throughout the study, both groups will continue the weekly self-administered subcutaneous MTX treatment, remaining on the preinclusion dosage (15-25 mg/week). The clinical measures of psoriasis and PsA disease activity used include the Short (2-page) Health Assessment Questionnaire, the Dermatology Quality of Life Index, the Spondyloarthritis Research Consortium of Canada Enthesitis Index, the Psoriasis Area Severity Index, a dactylitis digit count, a swollen/tender joint count (66/68), plasma C reactive protein as well as visual analogue scales for pain, fatigue and patient and physician global assessments. The primary end point is the proportion of patients who experience treatment failure during the 6-month trial period. The number of adverse events will be registered throughout the study.

ETHICS AND DISSEMINATION: This is a proof-of-concept clinical trial and will be performed in agreement with Good Clinical Practice standards. Approvals have been obtained from the local Ethics Committee (DK-S-20150080) and the Danish Data Protection Agency (15/41684). The study has commenced in May 2017. Dissemination will be through presentations at national and international conferences and through publications in international peer-reviewed journal(s).

TRIAL REGISTRATION NUMBER: NCT03058900; Pre-results.

BACKGROUND: Observational studies have shown that body mass index (BMI) is positively associated with asthma. However, observational data are prone to confounding and reverse causation. In Mendelian randomization, genetic variants are used as unconfounded markers of exposures to examine causal effects. We examined the causal effect of BMI on asthma, hay fever, allergic sensitization, serum total immunoglobulin E (IgE), forced expiratory volume in one-second (FEV1) and forced vital capacity (FVC).

METHODS: We included 490 497 participants in the observational and 162 124 participants in the genetic analyses. A genetic risk score (GRS) was created using 26 BMI-associated single nucleotide polymorphisms (SNPs). Results were pooled in meta-analyses and expressed as odds ratios (ORs) or β-estimates with 95% confidence interval (CI).

RESULTS: The GRS was significantly associated with asthma (OR=1.009; 95% CI: 1.004, 1.013), but not with hay fever (OR= 0.998; 95% CI: 0.994, 1.002) or allergic sensitization (OR=0.999; 95% CI: 0.986, 1.012) per BMI-increasing allele. The GRS was significantly associated with decrease in FEV1: β=-0.0012 (95% CI: -0.0019, -0.0006) and FVC: β=-0.0022 (95% CI: -0.0031, -0.0014) per BMI-increasing allele. Effect sizes estimated by instrumental variable analyses were OR=1.07 (95% CI: 1.03, 1.10) for asthma, a 9 ml decrease in FEV1 (95% CI: 2.0-15 mL decrease) and a 16 ml decrease in FVC (95% CI: 7.0-24 mL decrease) per 1 kg/m(2) higher BMI.

CONCLUSIONS: The results support the conclusion that increasing BMI is causally related to higher prevalence of asthma and decreased lung function, but not with hay fever or biomarkers of allergy.

INTRODUCTION: The number of persons living with a chronic condition is increasing worldwide. Conditions are considered chronic when lasting 1 year or more and requiring ongoing medical attention and/or limiting activities of daily living (ADL). Besides medical treatment, physical exercise to improve body functions is recommended and prescribed. However, improvements in body functions do not necessarily improve ability to perform ADL. Thus, it is necessary to develop interventions aiming directly at enhancing ADL ability. As a part of the research programme 'A Better Everyday Life', the first version of the ABLE intervention programme was developed.

METHODS AND ANALYSIS: This feasibility study examine the perceived value and acceptability of the ABLE programme by evaluating the fidelity, reach, dose and potential outcomes using a pretest and post-test design involving 30 persons living with chronic conditions. Qualitative interviews among occupational therapists delivering and participants receiving the ABLE programme will be conducted to explore aspects affecting the intervention.

ETHICS AND DISSEMINATION: The results will form the base for refinement of the ABLE programme and planning of a large-scale randomised controlled trial investigating the effect of the programme on self-reported and observed ADL ability. Dissemination will include peer-reviewed publications and presentations at national and international conferences.

PROTOCOL VERSION: 7 November 2017: v ersion 1.0. 19 February 2018: v ersion 2.0.

TRIAL REGISTRATION NUMBER: NCT03335709; Pre-results.