Patients' experience of shoulder disorders: a systematic review of qualitative studies for the OMERACT Shoulder Core Domain Set.

OBJECTIVES:To describe the experiences (including symptoms and perceived impacts on daily living) of people with a shoulder disorder. METHODS:Systematic review of qualitative studies. We searched for eligible qualitative studies indexed in Ovid MEDLINE, Ovid Embase, CINAHL (EBSCO), SportDiscus (EBSCO) and Ovid PsycINFO up until November 2017. Two authors independently screened studies for inclusion, appraised their methodological quality using the Critical Appraisal Skills Programme checklist, used thematic synthesis methods to generate themes describing the experiences reported by participants and assessed the confidence in the findings using the Grading of Recommendations Assessment, Development and Evaluation Confidence in Evidence from Reviews of Qualitative research (GRADE-CERQual) approach. RESULTS:The inclusion criteria were met by eight studies, which included 133 participants (49 females and 84 males) with either rotator cuff disease, adhesive capsulitis, proximal humeral fracture, shoulder instability or unspecified shoulder pain. We generated seven themes to describe what people in the included studies reported experiencing: pain; physical function/activity limitations; participation restriction; sleep disruption; cognitive dysfunction; emotional distress; and other pathophysiological manifestations (other than pain). There were interactions between the themes, with particular experiences impacting on others (e.g. pain leading to reduced activities and sleep disruption). Following grading of the evidence, we considered it likely that most of the review findings were a reasonable representation of the experiences of people with shoulder disorders. CONCLUSION:Patients with shoulder disorders contend with considerable disruption to their life. The experiences described should be considered by researchers seeking to select the most appropriate outcomes to measure in clinical trials and other research studies in people with shoulder disorders

The OMERACT Core Domain Set for Clinical Trials of Shoulder Disorders.

OBJECTIVE:To reach consensus on the core domains to be included in a core domain set for clinical trials of shoulder disorders using the Outcome Measures in Rheumatology (OMERACT) Filter 2.1 Core Domain Set process. METHODS:At OMERACT 2018, the OMERACT Shoulder Working Group conducted a workshop that presented the OMERACT 2016 preliminary core domain set and its rationale based upon a systematic review of domains measured in shoulder trials and international Delphi sessions involving patients, clinicians, and researchers, as well as a new systematic review of qualitative studies on the experiences of people with shoulder disorders. After discussions in breakout groups, the OMERACT core domain set for clinical trials of shoulder disorders was presented for endorsement by OMERACT 2018 participants. RESULTS:The qualitative review (n = 8) identified all domains included in the preliminary core set. An additional domain, cognitive dysfunction, was also identified, but confidence that this represents a core domain was very low. The core domain set that was endorsed by the OMERACT participants, with 71% agreement, includes 4 "mandatory" trial domains: pain, function, patient global - shoulder, and adverse events including death; and 4 "important but optional" domains: participation (recreation/work), sleep, emotional well-being, and condition-specific pathophysiological manifestations. Cognitive dysfunction was voted out of the core domain set. CONCLUSION:OMERACT 2018 delegates endorsed a core domain set for clinical trials of shoulder disorders. The next step includes identification of a core outcome measurement set that passes the OMERACT 2.1 Filter for measuring each domain

Assessing the reliability of retrospective reports of adverse childhood experiences among adolescents with documented childhood maltreatment

The literature suggests that childhood maltreatment is related to a higher probability of developing psychopathology and disease in adulthood. However, some authors have questioned the reliability of self-reports of maltreatment, suggesting that psychopathology at the time of evaluation affects self-reports. We evaluated the reliability of the self-reports of 79 young adults who were identified in childhood by Child Protective Services by comparing two moments of evaluation. Psychological and physical symptoms were tested to evaluate their interference with the reports. We found good to excellent agreement, with no significant correlation between the changes in self-reported experiences and the changes in physical and psychological symptoms, suggesting that the reliability of reports is not related to the health state at the time of the report

Applying science in practice: the optimization of biological therapy in rheumatoid arthritis

Most authorities recommend starting biological agents upon failure of at least one disease-modifying agent in patients with rheumatoid arthritis. However, owing to the absence of head-to-head studies, there is little guidance about which biological to select. Still, the practicing clinician has to decide. This review explores the application of published evidence to practice, discussing the goals of treatment, the (in) ability to predict individual responses to therapy, and the potential value of indirect comparisons. We suggest that cycling of biological agents, until remission is achieved or until the most effective agent for that individual patient is determined, deserves consideration in the current stage of knowledge

AID-Targeting and Hypermutation of Non-Immunoglobulin Genes Does Not Correlate with Proximity to Immunoglobulin Genes in Germinal Center B Cells

Upon activation, B cells divide, form a germinal center, and express the activation induced deaminase (AID), an enzyme that triggers somatic hypermutation of the variable regions of immunoglobulin (Ig) loci. Recent evidence indicates that at least 25% of expressed genes in germinal center B cells are mutated or deaminated by AID. One of the most deaminated genes, c-Myc, frequently appears as a translocation partner with the Ig heavy chain gene (Igh) in mouse plasmacytomas and human Burkitt's lymphomas. This indicates that the two genes or their double-strand break ends come into close proximity at a biologically relevant frequency. However, the proximity of c-Myc and Igh has never been measured in germinal center B cells, where many such translocations are thought to occur. We hypothesized that in germinal center B cells, not only is c-Myc near Igh, but other mutating non-Ig genes are deaminated by AID because they are near Ig genes, the primary targets of AID. We tested this “collateral damage” model using 3D-fluorescence in situ hybridization (3D-FISH) to measure the distance from non-Ig genes to Ig genes in germinal center B cells. We also made mice transgenic for human MYC and measured expression and mutation of the transgenes. We found that there is no correlation between proximity to Ig genes and levels of AID targeting or gene mutation, and that c-Myc was not closer to Igh than were other non-Ig genes. In addition, the human MYC transgenes did not accumulate mutations and were not deaminated by AID. We conclude that proximity to Ig loci is unlikely to be a major determinant of AID targeting or mutation of non-Ig genes, and that the MYC transgenes are either missing important regulatory elements that allow mutation or are unable to mutate because their new nuclear position is not conducive to AID deamination

Activation-Induced Cytidine Deaminase Expression in CD4+ T Cells is Associated with a Unique IL-10-Producing Subset that Increases with Age

Activation-induced cytidine deaminase (AID), produced by the Aicda gene, is essential for the immunoglobulin gene (Ig) alterations that form immune memory. Using a Cre-mediated genetic system, we unexpectedly found CD4+ T cells that had expressed Aicda (exAID cells) as well as B cells. ExAID cells increased with age, reaching up to 25% of the CD4+ and B220+ cell populations. ExAID B cells remained IgM+, suggesting that class-switched memory B cells do not accumulate in the spleen. In T cells, AID was expressed in a subset that produced IFN-γ and IL-10 but little IL-4 or IL-17, and showed no evidence of genetic mutation. Interestingly, the endogenous Aicda expression in T cells was enhanced in the absence of B cells, indicating that the process is independent from the germinal center reaction. These results suggest that in addition to its roles in B cells, AID may have previously unappreciated roles in T-cell function or tumorigenesis