Personal non-commercial use only

ABSTRACT. Objective. To develop an innovative stepped patient decision aid (StDA) comparing the benefits and harms of 13 nonsurgical treatment options for managing osteoarthritis (OA) and to evaluate its acceptability and effects on informed decision making. Methods. Guided by the Ottawa Decision Support Framework and the International Patient Decision Aid Standards, the process involved (1) developing a decision aid with evidence on 13 nonsurgical treatments from the 2012 American College of Rheumatology OA clinical practice guidelines; and (2) interviewing patients with OA and healthcare providers to test its acceptability and effects on knowledge and decisional conflict. Results. The StDA helped make the decision explicit, and presented evidence on 13 OA treatments clustered into 5 steps or levels according to their benefits and harms. Probabilities of benefits and harms were presented using pictograms of 100 faces formatted to allow comparisons across sets of options. It also included a values clarification exercise and knowledge test. Feedback was obtained from 49 patients and 7 healthcare providers. They found that the StDA presented evidence in a clear manner, and helped patients clarify their values and make an informed decision. Some participants found that there was too much information and others said that there was not enough on each treatment option. Conclusion. This innovative StDA allows patients to consider both the evidence and their values for multiple options. The findings are being used to revise and plan future evaluation. The StDA is an example of how research evidence in guidelines can be implemented in practice

Identifying flares in rheumatoid arthritis: Reliability and construct validation of the OMERACT RA Flare Core Domain Set

Objective: To evaluate the reliability of concurrent flare identification using 3 methods (patient, rheumatologist and Disease Activity Score (DAS)28 criteria), and construct validity of candidate items representing the Outcome Measures in Rheumatology Clinical Trials (OMERACT) RA Flare Core Domain Set. Methods: Candidate flare questions and legacy measures were administered at consecutive visits to Canadian Early Arthritis Cohort (CATCH) patients between November 2011 and November 2014. The American College of Rheumatology (ACR) core set indicators were recorded. Concordance to identify flares was assessed using the agreement coefficient. Construct validity of flare questions was examined: convergent (Spearman's r); discriminant (mean differences between flaring/non-flaring patients); and consequential (proportions with prior treatment reductions and intended therapeutic change postflare). Results: The 849 patients were 75% female, 81% white, 42% were in remission/low disease activity (R/LDA), and 16-32% were flaring at the second visit. Agreement of flare status was low-strong (κ's 0.17-0.88) and inversely related to RA disease activity level. Flare domains correlated highly (r's≥0.70) with each other, patient global (r's≥0.66) and corresponding measures (r's 0.49-0.92); and moderately highly with MD and patient-reported joint counts (r's 0.29-0.62). When MD/patients agreed the patient was flaring, mean flare domain between-group differences were 2.1-3.0; 36% had treatment reductions prior to flare, with escalation planned in 61%. Conclusions: Flares are common in rheumatoid arthritis (RA) and are often preceded by treatment reductions. Patient/MD/DAS agreement of flare status is highest in patients worsening from R/LDA. OMERACT RA flare questions can discriminate between patients with/without flare and have strong evidence of construct and consequential validity. Ongoing work will identify optimal scoring and cut points to identify RA flares

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Zika virus infection in pregnancy: a protocol for the joint analysis of the prospective cohort studies of the ZIKAlliance, ZikaPLAN and ZIKAction consortia

INTRODUCTION: Zika virus (ZIKV) infection in pregnancy has been associated with microcephaly and severe neurological damage to the fetus. Our aim is to document the risks of adverse pregnancy and birth outcomes and the prevalence of laboratory markers of congenital infection in deliveries to women experiencing ZIKV infection during pregnancy, using data from European Commission-funded prospective cohort studies in 20 centres in 11 countries across Latin America and the Caribbean. METHODS AND ANALYSIS: We will carry out a centre-by-centre analysis of the risks of adverse pregnancy and birth outcomes, comparing women with confirmed and suspected ZIKV infection in pregnancy to those with no evidence of infection in pregnancy. We will document the proportion of deliveries in which laboratory markers of congenital infection were present. Finally, we will investigate the associations of trimester of maternal infection in pregnancy, presence or absence of maternal symptoms of acute ZIKV infection and previous flavivirus infections with adverse outcomes and with markers of congenital infection. Centre-specific estimates will be pooled using a two-stage approach. ETHICS AND DISSEMINATION: Ethical approval was obtained at each centre. Findings will be presented at international conferences and published in peer-reviewed open access journals and discussed with local public health officials and representatives of the national Ministries of Health, Pan American Health Organization and WHO involved with ZIKV prevention and control activities

Reduction in Serum Uric Acid May Be Related to Methotrexate Efficacy in Early Rheumatoid Arthritis: Data from the Canadian Early Arthritis Cohort (CATCH)

Objectives The mechanism of action of methotrexate in rheumatoid arthritis (RA) is complex. It may increase adenosine levels by blocking its conversion to uric acid (UA). This study was done to determine if methotrexate lowers UA in early RA (ERA). Methods Data were obtained from Canadian Early Arthritis Cohort, an incident ERA cohort. All ERA patients with serial UA measurements were included, comparing those with methotrexate use vs. no methotrexate exposure (controls). Analyses were exploratory. Patients with concomitant gout or taking UA-lowering therapies were excluded. Results In total, 49 of the 2,524 ERA patients were identified with data available for both pre-methotrexate UA levels and post-methotrexate UA levels (300 μmol/L and 273 μmol/L, respectively; P = 0.035). The control group not taking methotrexate had a mean baseline UA level of 280 μmol/L and a follow-up level of 282 μmol/L ( P = 0.448); mean change in UA with methotrexate was -26.8 μmol/L vs. 2.3 μmol/L in the no methotrexate group ( P = 0.042). Methotrexate users with a decrease in UA had a disease activity score of 2.37 for 28 joints when compared with the controls (3.26) at 18 months ( P = 0.042). Methotrexate users with decreased UA had a lower swollen joint count (SJC) of 0.9 at 18 months, whereas methotrexate users without lowering of UA had an SJC of 4.5 ( P = 0.035). Other analyses were not significant. Conclusions Methotrexate response is associated with lowering of serum UA in ERA compared to nonusers. This may be due to changes in adenosine levels. Methotrexate response is associated with lower UA and fewer swollen joints compared to nonresponders

Reduction in Serum Uric Acid may be Related to Methotrexate Efficacy in Early Rheumatoid Arthritis: Data from the Canadian Early Arthritis Cohort (CATCH)

Objectives The mechanism of action of methotrexate in rheumatoid arthritis (RA) is complex. It may increase adenosine levels by blocking its conversion to uric acid (UA). This study was done to determine if methotrexate lowers UA in early RA (ERA). Methods Data were obtained from Canadian Early Arthritis Cohort, an incident ERA cohort. All ERA patients with serial UA measurements were included, comparing those with methotrexate use vs. no methotrexate exposure (controls). Analyses were exploratory. Patients with concomitant gout or taking UA-lowering therapies were excluded. Results In total, 49 of the 2,524 ERA patients were identified with data available for both pre-methotrexate UA levels and post-methotrexate UA levels (300 μmol/L and 273 μmol/L, respectively; P = 0.035). The control group not taking methotrexate had a mean baseline UA level of 280 μmol/L and a follow-up level of 282 μmol/L ( P = 0.448); mean change in UA with methotrexate was -26.8 μmol/L vs. 2.3 μmol/L in the no methotrexate group ( P = 0.042). Methotrexate users with a decrease in UA had a disease activity score of 2.37 for 28 joints when compared with the controls (3.26) at 18 months ( P = 0.042). Methotrexate users with decreased UA had a lower swollen joint count (SJC) of 0.9 at 18 months, whereas methotrexate users without lowering of UA had an SJC of 4.5 ( P = 0.035). Other analyses were not significant. Conclusions Methotrexate response is associated with lowering of serum UA in ERA compared to nonusers. This may be due to changes in adenosine levels. Methotrexate response is associated with lower UA and fewer swollen joints compared to nonresponders

Personal non-commercial use only

ABSTRACT. Objective. To develop an innovative stepped patient decision aid (StDA) comparing the benefits and harms of 13 nonsurgical treatment options for managing osteoarthritis (OA) and to evaluate its acceptability and effects on informed decision making