Treatable traits and exacerbation risk in patients with uncontrolled asthma prescribed GINA step 1-3 treatment: A nationwide asthma cohort study.

BACKGROUND AND OBJECTIVE: Uncontrolled asthma in patients treated for mild/moderate disease could be caused by non-pulmonary treatable traits (TTs) that affect asthma control negatively. We aimed to identify demographic characteristics, behavioural (smoking) and extrapulmonary (obesity, comorbidities) TTs and the risk for future exacerbations among patients with uncontrolled asthma prescribed step 1-3 treatment according to the Global Initiative for Asthma (GINA). METHODS: Twenty-eight thousand five hundred eighty-four asthma patients (≥18 y) with a registration in the Swedish National Airway Register between 2017 and 2019 were included (index-date). The database was linked to other national registers to obtain information on prescribed drugs 2-years pre-index and exacerbations 1-year post-index. Asthma treatment was classified into step 1-3 or 4-5, and uncontrolled asthma was defined based on symptom control, exacerbations and lung function. RESULTS: GINA step 1-3 included 17,318 patients, of which 9586 (55%) were uncontrolled (UCA 1-3). In adjusted analyses, UCA 1-3 was associated with female sex (OR 1.34, 95% CI 1.27-1.41), older age (1.00, 1.00-1.00), primary education (1.30, 1.20-1.40) and secondary education (1.19, 1.12-1.26), and TTs such as smoking (1.25, 1.15-1.36), obesity (1.23, 1.15-1.32), cardiovascular disease (1.12, 1.06-1.20) and depression/anxiety (1.13, 1.06-1.21). Furthermore, UCA 1-3 was associated with future exacerbations; oral corticosteroids (1.90, 1.74-2.09) and asthma hospitalization (2.55, 2.17-3.00), respectively, also when adjusted for treatment step 4-5. CONCLUSION: Over 50% of patients treated for mild/moderate asthma had an uncontrolled disease. Assessing and managing of TTs such as smoking, obesity and comorbidities should be conducted in a holistic manner, as these patients have an increased risk for future exacerbations.

Genome-wide association study of liver enzyme elevation in an extended cohort of rheumatoid arthritis patients starting low-dose methotrexate.

Aim: A follow-up genome-wide association study (GWAS) in an extended cohort of rheumatoid arthritis (RA) patients starting low-dose methotrexate (MTX) treatment was performed to identify further genetic variants associated with alanine aminotransferase (ALT) elevation. Patients & methods: A GWAS was performed on 346 RA patients. Two outcomes within the first 6 months of MTX treatment were assessed: ALT >1.5-times the upper level of normal (ULN) and maximum level of ALT. Results: SPATA9 (rs72783407) was significantly associated with maximum level of ALT (p = 2.58 × 10-8) and PLCG2 (rs60427389) was tentatively associated with ALT >1.5 × ULN. Conclusion: Associations with SNPs in genes related to male fertility (SPATA9) and inflammatory processes (PLCG2) were identified.

Genome-wide association study of liver enzyme elevation in rheumatoid arthritis patients starting methotrexate.

Aim: To identify novel genetic variants predisposing to elevation of Alanine aminotransferase (ALT) in rheumatoid arthritis (RA) patients after initiation of methotrexate (MTX) treatment. Patients & methods: We performed genome-wide association studies in 198 RA patients starting MTX. Outcomes were maximum level of ALT and ALT >1.5-times the upper level of normal within the first 6 months of treatment. Results:RAVER2 (rs72675408) was significantly associated with maximum level of ALT (p = 4.36 × 10-8). This variant is in linkage disequilibrium with rs72675451, which is associated with differential expression of JAK1 and RAVER2. Conclusion: We found an association between ALT elevation and genetic variants that may regulate the expression of JAK1 and RAVER2. JAK1 encodes a janus kinase involved in the pathogenesis of RA.

Tuberculosis in Biologic-naïve Patients With Rheumatoid Arthritis: Risk Factors and Tuberculosis Characteristics.

OBJECTIVE: To investigate risk factors and characteristics of active tuberculosis (TB) in biologic-naïve patients with rheumatoid arthritis (RA). METHODS: We conducted a population-based case-control study using the Swedish Rheumatology Quality Register, the National Patient Register, and the Tuberculosis Register to identify RA patients with active TB and matched RA controls without TB between 2001-2014. Clinical data were obtained from medical records. TB risk was estimated as adjusted OR (aOR) with 95% CI using univariate and multivariable logistic regression analyses. RESULTS: After validation of diagnoses, the study included 31 RA patients with TB and 122 matched RA controls. All except 3 cases had reactivation of latent TB. Pulmonary TB was most prevalent (84%). Ever use of methotrexate was not associated with increased TB risk (aOR 0.8, 95% CI 0.3-2.0), whereas ever treatment with leflunomide (aOR 6.0, 95% CI 1.5-24.7), azathioprine (aOR 3.8, 95% CI 1.1-13.8), and prednisolone (PSL; aOR 2.4, 95% CI 1.0-6.0) was. There were no significant differences between maximum dose of PSL, treatment duration with PSL before TB, or cumulative dose of PSL the year before TB diagnosis between cases and controls. Obstructive pulmonary disease was associated with an increased TB risk (aOR 3.9, 95% CI 1.5-10.7). CONCLUSION: Several RA-associated factors may contribute to increased TB risk in biologic-naïve patients with RA, making the risk of TB activation difficult to predict in the individual patient. To further decrease TB in patients with RA, the results suggest that screening for latent TB should also be considered in biologic-naïve patients.

MTHFR, TYMS and SLCO1B1 polymorphisms and adverse liver effects of methotrexate in rheumatoid arthritis.

Aims: To investigate whether variants of MTHFR, TYMS and SLCO1B1 are associated with ALT elevation in rheumatoid arthritis patients starting methotrexate (MTX). Patients & methods: Clinical and laboratory data were collected from the start of MTX treatment. Genotyping of MTHFR, TYMS and SLCO1B1 was performed. Univariate and multiple logistic regression were used for statistical analysis. Results: 34 out of 369 patients experienced ALT >1.5 × ULN less than 6 months from start. MTHFR A1298C (rs1801131) was nominally associated with an ALT >1.5 × ULN within 6 months after the start of MTX (OR = 1.7 [95% CI: 1.04-2.9]; p = 0.03), but did not pass correction for multiple testing. A multiple model containing MTHFR 1298C and clinical factors predicted the outcome (C-statistic 0.735). TYMS and SLCO1B1 were not associated with the outcome. Conclusions: A model containing MTHFR 1298C and clinical factors might predict risk of early ALT elevation.

Nursing Students' Reflections After Meetings With Patients and Their Relatives Enacted by Professional Actors: Being Touched and Feeling Empathy.

When professional actors have been used in mental health simulations with nursing students, the experience has been regarded as a meaningful contribution to their education and described as a safe way of experiencing challenging situations that can occur in clinical settings. The aim was to study nursing students' reflections after meetings with nursing patients and their relatives, as enacted by professional actors, in psychiatric/elderly care. The design was a qualitative descriptive research approach. Gibbs's ( 1988 ) reflective cycle was the basis for the questions that were asked. Written reflections with 60 nursing students were analysed using qualitative thematic content analysis. The analysis produced the theme "being touched and feeling empathy," with four categories: "becoming aware of what knowledge and skills are needed," "wanting to do well and to have the right answer," "daring to get close and being present," and "knowledge comes alive." Simulation with real people who act as patients or relatives in vulnerable situations creates feelings of empathy. To talk with them, experience eye contact, and see how they react on touch makes nursing students feel they have experienced closeness and their knowledge has become alive.