IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes.

GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 candidate genes in 6600 Crohn disease (CD) cases and 5500 controls, and show with burden tests that they include likely causative genes. Our analyses indicate that ≥10-fold larger sample sizes will be required to demonstrate the causality of individual genes using this approach

Validation of two PROMIS item banks for measuring social participation in the Dutch general population

Background: The Patient-Reported Outcomes Measurement Information System (PROMIS) item banks ‘Ability to Participate in Social Roles and Activities’ (35 items) and ‘Satisfaction with Social Roles and Activities’ (44 items) were developed to measure (satisfaction with) participation more efficiently and precisely than current instruments, by using Computerized Adaptive Testing (CAT). We validated these item banks in a Dutch general population. Methods: Participants in an internet panel completed both item banks. Unidimensionality, local dependence, monotonicity, Graded Response Model item fit, Differential Item Functioning (DIF) for age, gender, education, region, ethnicity, and language (Dutch compared to US Social Supplement), and reliability were assessed. Results: A representative Dutch sample of 1002 people participated. We found for the Ability to Participate and Satisfaction with Participation item banks, respectively, sufficient unidimensionality (CFI: 0.971, 0.960; TLI: 0.970, 0.958; RMSEA: 0.108, 0.108), no local dependence, sufficient monotonicity (H: 0.75, 0.73), good item fit (2 out of 35 items, 1 out of 44 items with S-X2p-value < 0.001). No DIF was found. We found a reliability of at least 0.90 with simulated CATs in 86% and 94% of the participants with on average 4.7 (range 2–12) and 4.3 (range 3–12) items, respectively. Discussion: The PROMIS participation item banks showed sufficient psychometric properties in a general Dutch population and can be used as CAT. PROMIS CATs allow reliable and valid measurement of participation in an efficient and user-friendly way with limited administration time

Dutch reference values for the Patient-Reported Outcomes Measurement Information System Scale v1.2 - Global Health (PROMIS-GH)

Background: To add context to the impact of medical conditions, it is important to interpret and compare health outcomes across studies and populations. We aimed to determine Dutch reference values for the Patient-Reported Outcomes Measurement Information System Scale v1.2 - Global Health (PROMIS-GH). Methods: The PROMIS-GH, also referred to as PROMIS-10, was completed by 4370 Dutch persons, representative for the 2016 Dutch population. T-scores for the mental health (GMH) and physical health (GPH) subscales, and their shorter two-item subscales, were calculated for the entire population, age groups and gender. T-scores for GMH and GPH were compared to the US reference population, representative for the 2000 US general population. Interpretability thresholds for poor, fair, good, very good and excellent GPH and GMH were calculated based on T-scores of participants, which were categorized into five groups based on their response to item Global01. For each group the mean GPH and GMH T-score was calculated and the midpoint between two adjacent means was identified, resulting in thresholds. Thresholds based on the Dutch data were compared to US thresholds. Results: The Dutch population had a GMH T-score of 44.7 and a GPH T-score of 45.2, both substantially worse than the US reference population T-score of 50. Lower T-scores were also found for age-range and gender subpopulations. Dutch GMH and GPH interpretability thresholds were mostly not substantially different compared to the US thresholds, although the Dutch threshold between fair and poor mental health was considerably higher (29 vs. 38). Conclusions: This study reports reference values for the PROMIS-GH scale for the Dutch general population, including age-range and gender subpopulations. These reference values provide an important tool for healthcare professionals and researchers to better evaluate and interpret patient-reported mental health and physical health. Scores are notably worse than the US reference values. The exact reason for this remains subject for further research, although possibilities for the differences are discussed, including the presence of differential item functioning and the representativeness and recentness of the data

Effect of robotic gait training on cardiorespiratory system in incomplete spinal cord injury

The objectives in this study were to investigate the effect of robot-assisted gait training on cardiorespiratory fitness in subjects with motor incomplete spinal cord injury and document the exercise intensity of robotic walking in comparison with the recommended guidelines. Ten patients followed a 24-session training program with a robotic gait orthosis in addition to physiotherapy sessions completed within 10 to 16 wk. Cardiorespiratory fitness was determined in a graded arm crank exercise test before and after the training program. To assess the intensity of robot-assisted walking, oxygen consumption (VO2) and heart rate (HR) were measured during a training session early in and at the end of the training program, and exercise intensity measures (percentage of VO2 reserve [%VO2R], percentage of HR reserve [%HRR], and metabolic equivalents [METs]) were calculated. Whereas no changes were found in peak VO2, the resting and submaximal HR at a constant work load were significantly lower after training. Most subjects exercised at low intensity (3.0 METs). In spite of the low exercise intensity of the training program and no changes in peak VO2, robot-assisted gait training induced some improvement in cardiorespiratory fitness, as suggested by lower resting and submaximal HR values