Rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis epidemiology in England from 2004 to 2020: An observational study using primary care electronic health record data.

Background: Contemporary data on rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritits (SpA) epidemiology in England are lacking. This knowledge is crucial to planning healthcare services. We updated algorithms defining patients with diagnoses of RA, PsA, and axial SpA in primary care and applied them to describe their incidence and prevalence in the Clinical Practice Research Datalink Aurum, an electronic health record (EHR) database covering ∼20% of England. Methods: Algorithms for ascertaining patients with RA, axial SpA, and PsA diagnoses validated in primary care EHR databases using Read codes were updated (to account for the English NHS change to SNOMED CT diagnosis coding) and applied. Updated diagnosis and synthetic disease-modifying anti-rheumatic drug code lists were devised by rheumatologists and general practitioners. Annual incidence/point-prevalence of RA, PsA, and axial SpA diagnoses were calculated from 2004 to 2020 and stratified by age/sex. Findings: Point-prevalence of RA/PsA diagnoses increased annually, peaking in 2019 (RA 0·779% [95% confidence interval (CI) 0·773, 0·784]; PsA 0·287% [95% CI 0·284, 0·291]) then falling slightly. Point-prevalence of axial SpA diagnoses increased annually (except in 2018/2019), peaking in 2020 (0·113% [95% CI 0·111, 0·115]). RA diagnosis annual incidence was higher between 2013-2019 (after inclusion in the Quality and Outcomes Framework, range 49·1 [95% CI 47·7, 50·5] to 52·1 [95% CI 50·6, 53·6]/100,000 person-years) than 2004-2012 (range 34·5 [95% CI 33·2, 35·7] to 40·0 [95% CI 38·6, 41·4]/100,000 person-years). Increases in the annual incidence of PsA/axial SpA diagnosis occurred following new classification criteria publication. Annual incidence of RA, PsA and axial SpA diagnoses fell by 40·1%, 67·4%, and 38·1%, respectively between 2019 and 2020, likely reflecting the COVID-19 pandemic's impact on their diagnosis. Interpretation: Recorded RA, PsA, and axial SpA diagnoses are increasingly prevalent in England, underlining the importance of organising healthcare services to provide timely, treat-to-target care to optimise the health of >1% of adults in England. Funding: National Institute for Health and Care Research (NIHR300826)

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

Sex-differential impact of human cytomegalovirus infection on in vitro reactivity to toll-like receptor 2, 4 and 7/8 stimulation in Gambian infants

Human cytomegalovirus (HCMV) infection rates approach 100% by the first year of lifein low-income countries. It is not known if this drives changes to innate immunity in early life andthereby altered immune reactivity to infections and vaccines. Given the panoply of sex differences inimmunity, it is feasible that any immunological effects of HCMV would differ in males and females.We analysed ex vivo innate cytokine responses to a panel of toll-like receptor (TLR) ligands in 108nine-month-old Gambian males and females participating in a vaccine trial. We found evidencethat HCMV suppressed reactivity to TLR2 and TLR7/8 stimulation in females but not males. Thisis likely to contribute to sex differences in responses to infections and vaccines in early life and hasimplications for the development of TLR ligands as vaccine adjuvants. Development of an effectiveHCMV vaccine would be able to circumvent some of these potentially negative effects of HCMVinfection in childhood

A mutation in the viral sensor 2'-5'-oligoadenylate synthetase 2 causes failure of lactation.

We identified a non-synonymous mutation in Oas2 (I405N), a sensor of viral double-stranded RNA, from an ENU-mutagenesis screen designed to discover new genes involved in mammary development. The mutation caused post-partum failure of lactation in healthy mice with otherwise normally developed mammary glands, characterized by greatly reduced milk protein synthesis coupled with epithelial cell death, inhibition of proliferation and a robust interferon response. Expression of mutant but not wild type Oas2 in cultured HC-11 or T47D mammary cells recapitulated the phenotypic and transcriptional effects observed in the mouse. The mutation activates the OAS2 pathway, demonstrated by a 34-fold increase in RNase L activity, and its effects were dependent on expression of RNase L and IRF7, proximal and distal pathway members. This is the first report of a viral recognition pathway regulating lactation

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

A low proportion of HBeAg among HBsAg-positive pregnant women with known HIV status could suggest low perinatal transmission of HBV in Cameroon

<p>Abstract</p> <p>Background</p> <p>Transmission of hepatitis B virus (HBV) from HBV-positive mothers to their infants is common and usually occurs when the mother is hepatitis B e antigen (HBeAg) positive and/or has a high HBV DNA load. In this study, we determined the prevalence of hepatitis B surface antigen (HBsAg) and HBeAg among pregnant women with known HIV status.</p> <p>Findings</p> <p>A total of 650 pregnant women with a mean age of 26.2 years including 301 HIV-positives and 349 HIV-negatives were screened for HBsAg (Monolisa AgHBs Plus Biorad, France). Among the HBsAg-positives, HBeAg and anti-HBe were tested (Monolisa Ag HBe Plus Biorad, France). Overall, 51 (7.85%) were positive for HBsAg. The prevalence of HBsAg was not statistically different between HIV-positive and HIV-negative pregnant women [28/301 (9.3%) vs 23/349 (6.59%); p = 0.2]. None of the 45 HBsAg-positive samples was reactive for HBeAg.</p> <p>Conclusions</p> <p>Our study indicates a high prevalence of HBsAg with very low proportion of HBeAg in Cameroonian pregnant women. Since perinatal transmission of HBV is mostly effective when the mother is also HBeAg-positive, our data could suggest that perinatal transmissions play a minor role in HBV prevalence in Cameroon. In line with previous African studies, these findings further suggests that horizontal transmission could be the most common mechanism of HBV infections in Cameroon.</p

Blood pro-resolving mediators are linked with synovial pathology and are predictive of DMARD responsiveness in rheumatoid arthritis.

Biomarkers are needed for predicting the effectiveness of disease modifying antirheumatic drugs (DMARDs). Here, using functional lipid mediator profiling and deeply phenotyped patients with early rheumatoid arthritis (RA), we observe that peripheral blood  specialized pro-resolving mediator (SPM) concentrations are linked with both DMARD responsiveness and disease pathotype. Machine learning analysis demonstrates that baseline plasma concentrations of resolvin D4, 10S, 17S-dihydroxy-docosapentaenoic acid, 15R-Lipoxin (LX)A4 and n-3 docosapentaenoic-derived Maresin 1 are predictive of DMARD responsiveness at 6 months. Assessment of circulating SPM concentrations 6-months after treatment initiation establishes that differences between responders and non-responders are maintained, with a decrease in SPM concentrations in patients resistant to DMARD therapy. These findings elucidate the potential utility of  plasma SPM concentrations as biomarkers of DMARD responsiveness in RA