Early recognition and detection of juvenile psoriatic arthritis: a call for a standardized approach to screening

Background: National Institute for Health and Care Excellence (NICE) guidelines recommend annual screening for psoriatic arthritis (PsA) in all patients with psoriasis. Currently, no validated assessment tools have been recommended for screening for juvenile PsA (JPsA). Aim: To determine dermatologists' practice when assessing children's joints and explore the challenges dermatologists experience when looking for joint disease, in order to inform future strategies to improve early detection of arthritis. Methods: Structured telephone interviews were undertaken with dermatologists identified through the British Society of Paediatric Dermatology. Percentages for binary and categorized responses were calculated. Thematic content analysis was used to generate a set of core themes across the interview data. Results: Of the 41 consultant dermatologists contacted, 23 agreed to be interviewed. Of these, 78% (18/23) reported they routinely ask about joint disease. Only 13% (3/23) routinely examine the joints of children with psoriasis. Overall, assessment for JPsA lacked a structured, evidence-based approach. The average confidence rating for assessing joint disease was low (score of 3). The two key barriers described for detecting arthritis were a lack of experience and training, and subtle or difficult to detect signs. The two main suggestions for improving detection were the introduction of an assessment tool/guideline and increased clinical experience and training. Conclusion: There is a clear need for dermatologists to use a standardized approach for screening and to increase their confidence in paediatric musculoskeletal examination. In this article, we provide guidance on screening for psoriatic arthritis in children based on our clinical experience

Protocol for a case-control diagnostic accuracy study to develop diagnostic criteria for psoriasis in children (DIPSOC study): a multicentre study recruiting in UK paediatric dermatology clinics

Introduction Diagnosing psoriasis in children can be challenging. Early and accurate diagnosis is important to ensure patients receive psoriasis specific treatment and monitoring. It is recognised that the physical, psychological, quality of life, financial and comorbid burden of psoriasis are significant. The aim of this study is to develop clinical examination and history-based diagnostic criteria for psoriasis in children to help differentiate psoriasis from other scaly inflammatory rashes. The criteria tested in this study were developed through a consensus study with a group of international psoriasis experts (International Psoriasis Council). Methods and analysis Children and young people (<18 years) with psoriasis (cases) and other scaly inflammatory skin diseases (controls) diagnosed by a dermatologist are eligible for recruitment. All participants complete a single research visit including a diagnostic criteria assessment by a trained investigator blinded to the participant’s diagnosis. The reference standard of a dermatologist’s diagnosis is extracted from the medical record. Sensitivity and specificity of the consensus derived diagnostic criteria will be calculated and the best predictive criteria developed using multivariate logistic regression. Ethics and dissemination Health Regulatory Authority and National Health Service Research Ethics Committee approvals were granted in February 2017 (REC Ref: 17/ EM/0035). Dissemination will be guided by stakeholders; patients, children and

Assessment of metabolic and mitochondrial dynamics in CD4+ and CD8+ T cells in virologically suppressed HIV-positive individuals on combination antiretroviral therapy

Metabolism plays a fundamental role in supporting the growth, proliferation and effector functions of T cells. We investigated the impact of HIV infection on key processes that regulate glucose uptake and mitochondrial biogenesis in subpopulations of CD4+ and CD8+ T cells from 18 virologically-suppressed HIV-positive individuals on combination antiretroviral therapy (cART; median CD4+ cell count: 728 cells/μl) and 13 HIV seronegative controls. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) production were also analysed in total CD4+ and CD8+ T cells. Among HIV+/cART individuals, expression of glucose transporter (Glut1) and mitochondrial density were highest within central memory and naïve CD4+ T cells, and lowest among effector memory and transitional memory T cells, with similar trends in HIV-negative controls. Compared to HIV-negative controls, there was a trend towards higher percentage of circulating CD4+Glut1+ T cells in HIV+/cART participants. There were no significant differences in mitochondrial dynamics between subject groups. Glut1 expression was positively correlated with mitochondrial density and MMP in total CD4+ T cells, while MMP was also positively correlated with ROS production in both CD4+ and CD8+ T cells. Our study characterizes specific metabolic features of CD4+ and CD8+ T cells in HIV-negative and HIV+/cART individuals and will invite future studies to explore the immunometabolic consequences of HIV infection

A systematic review of diagnostic criteria for psoriasis in adults and children: evidence from studies with a primary aim to develop or validate diagnostic criteria

Background: The diagnosis of psoriasis in adults and children is made clinically, for both patient management and the selection of participants in research. Diagnostic criteria provide a structure for clinical assessment, which in turn helps standardise patient recruitment into clinical trials and case definitions in observational studies.Objective: The aim of this systematic review was to identify and critically appraise the published studies to date that had a primary research aim to develop or validate diagnostic criteria for psoriasis.Method: A search of Ovid MEDLINE and Ovid Embase was conducted in October 2016. The primary objective was sensitivity and specificity of diagnostic criteria for psoriasis. Secondary objectives included diagnostic recommendations, applicability to children and study characteristics. Diagnostic accuracy studies were critically appraised for risk of bias using the QUADAS-2 tool.Results: Twenty-three studies met the inclusion criteria.None detailed clinical examination-based diagnostic criteria. The included criteria varied from genetic and molecular diagnostic models to skin imaging, histopathology, questionnaire-based, computer-aided and traditional Chinese medicine criteria. High sensitivity and specificity (>90%) were reported in many studies. However, the study authors often did not specify how criteria would be used clinically or in research. This review identified studies with varyingrisk of bias and due to each study developing separate criteria meta-analysis was not possible.Conclusion: Clinical examination-based diagnostic criteria are currently lacking for psoriasis. Future research could follow an international collaborative approach and employ high quality diagnostic accuracy study design. Existing and newly developed criteria require validation

Body mass index and treatment survival in patients with RA starting treatment with TNF alpha-inhibitors: long-term follow-up in the real-life METEOR registry

Objectives To study whether there is an association between body mass index (BMI) category and survival of various tumour necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA) patients in a real-life longitudinal international registry.Methods Data from 5230 patients with RA starting treatment with any TNFi were selected from the METEOR registry. Patients were divided into six BMI categories: 3.7% underweight, BMI40 kg/m(2). Time on treatment in the different BMI categories was compared for all TNFi combined and for the infliximab, adalimumab and etanercept separately, using Kaplan-Meier curves and Cox regression analyses. Cox regression analyses were adjusted for potential confounders, with follow-up censored at 5000 days.Results Patients in obesity class II (HR 1.28, 95% CI 1.06 to 1.54) and III (HR 1.67, 95% CI 1.29 to 2.18) and underweight patients (HR 1.30, 95% CI 1.07 to 1.58) showed statistically significantly shorter TNFi survival than normal weight patients. The effect in underweight patients was strongest for infliximab (HR 1.82, 95% CI 1.20 to 2.76), the effect in overweight patients was strongest for infliximab (category II (HR 1.49, 95% CI 0.98 to 2.26); category III (HR 1.46, 95% CI 0.79 to 2.71)) and etanercept (category II (HR 1.27 95% CI 0.98 to 1.65); category III (HR 1.79, 95% CI 1.25 to 2.55)). No significant effect modification from reported pain was found.Conclusion Both underweight and overweight patients discontinued TNFi treatment earlier than normal weight patients, without evidence of reported pain as the main determinant. It remains uncertain what determines TNFi survival in individual patients.Pathophysiology and treatment of rheumatic disease

Double-Layer Systems at Zero Magnetic Field

We investigate theoretically the effects of intralayer and interlayer exchange in biased double-layer electron and hole systems, in the absence of a magnetic field. We use a variational Hartree-Fock-like approximation to analyze the effects of layer separation, layer density, tunneling, and applied gate voltages on the layer densities and on interlayer phase coherence. In agreement with earlier work, we find that for very small layer separations and low layer densities, an interlayer-correlated ground state possessing spontaneous interlayer coherence (SILC) is obtained, even in the absence of interlayer tunneling. In contrast to earlier work, we find that as a function of total density, there exist four, rather than three, distinct noncrystalline phases for balanced double-layer systems without interlayer tunneling. The newly identified phase exists for a narrow range of densities and has three components and slightly unequal layer densities, with one layer being spin polarized, and the other unpolarized. An additional two-component phase is also possible in the presence of sufficiently strong bias or tunneling. The lowest-density SILC phase is the fully spin- and pseudospin-polarized ``one-component'' phase discussed by Zheng {\it et al.} [Phys. Rev. B {\bf 55}, 4506 (1997)]. We argue that this phase will produce a finite interlayer Coulomb drag at zero temperature due to the SILC. We calculate the particle densities in each layer as a function of the gate voltage and total particle density, and find that interlayer exchange can reduce or prevent abrupt transfers of charge between the two layers. We also calculate the effect of interlayer exchange on the interlayer capacitance.Comment: 35 pages, 19 figures included. To appear in PR

Plane-symmetric inhomogeneous magnetized viscous fluid universe with a variable Λ\Lambda

The behavior of magnetic field in plane symmetric inhomogeneous cosmological models for bulk viscous distribution is investigated. The coefficient of bulk viscosity is assumed to be a power function of mass density $(\xi =\xi_{0}\rho^{n})$. The values of cosmological constant for these models are found to be small and positive which are supported by the results from recent supernovae Ia observations. Some physical and geometric aspects of the models are also discussed.Comment: 18 pages, LaTex, no figur

Observation of exclusive DVCS in polarized electron beam asymmetry measurements

We report the first results of the beam spin asymmetry measured in the reaction e + p -> e + p + gamma at a beam energy of 4.25 GeV. A large asymmetry with a sin(phi) modulation is observed, as predicted for the interference term of Deeply Virtual Compton Scattering and the Bethe-Heitler process. The amplitude of this modulation is alpha = 0.202 +/- 0.028. In leading-order and leading-twist pQCD, the alpha is directly proportional to the imaginary part of the DVCS amplitude.Comment: 6 pages, 5 figure

Complete measurement of three-body photodisintegration of 3He for photon energies between 0.35 and 1.55 GeV

The three-body photodisintegration of 3He has been measured with the CLAS detector at Jefferson Lab, using tagged photons of energies between 0.35 GeV and 1.55 GeV. The large acceptance of the spectrometer allowed us for the first time to cover a wide momentum and angular range for the two outgoing protons. Three kinematic regions dominated by either two- or three-body contributions have been distinguished and analyzed. The measured cross sections have been compared with results of a theoretical model, which, in certain kinematic ranges, have been found to be in reasonable agreement with the data.Comment: 22 pages, 25 eps figures, 2 tables, submitted to PRC. Modifications: removed 2 figures, improvements on others, a few minor modifications to the tex