A Psychometric Evaluation of the Body Image Questionnaire Child and Adolescent Version.

Body dysmorphic disorder (BDD) typically develops during adolescence, but there has been little research evaluating assessment tools for BDD in youth. This study sought to provide a comprehensive psychometric evaluation of a brief self-report questionnaire of BDD symptoms, the Body Image Questionnaire Child and Adolescent version (BIQ-C), in both clinical and non-clinical adolescent samples. Properties of the BIQ-C were examined in 479 adolescents recruited through schools and 118 young people with BDD attending a specialist clinic. Sensitivity to change was additionally examined in a subgroup of the clinical sample who received treatment (n = 35). Exploratory factor analysis indicated that a two-factor structure provided the best fit for the data in the non-clinical sample. The two-factor solution was corroborated through confirmatory factor analysis as the best solution in the clinical sample, although it did not fulfil predefined fit thresholds The first factor encompassed preoccupation and repetitive behaviours, while the second included items assessing functional impairment. The BIQ-C showed good internal consistency across both samples, and convergent validity with other measures of BDD. Among those in the clinical sample who received treatment, BIQ-C scores decreased significantly, and BIQ-C change scores were highly correlated with change scores on the gold-standard clinician-rated measure of BDD symptom severity. These findings indicate that the BIQ-C is a suitable tool for assessing BDD symptoms in young people and measuring change during treatment.

Depression, anxiety and PTSD symptoms before and during the COVID-19 pandemic in the UK.

BACKGROUND: The impact of the coronavirus disease 2019 (COVID-19) pandemic on mental health is still being unravelled. It is important to identify which individuals are at greatest risk of worsening symptoms. This study aimed to examine changes in depression, anxiety and post-traumatic stress disorder (PTSD) symptoms using prospective and retrospective symptom change assessments, and to find and examine the effect of key risk factors. METHOD: Online questionnaires were administered to 34 465 individuals (aged 16 years or above) in April/May 2020 in the UK, recruited from existing cohorts or via social media. Around one-third (n = 12 718) of included participants had prior diagnoses of depression or anxiety and had completed pre-pandemic mental health assessments (between September 2018 and February 2020), allowing prospective investigation of symptom change. RESULTS: Prospective symptom analyses showed small decreases in depression (PHQ-9: -0.43 points) and anxiety [generalised anxiety disorder scale - 7 items (GAD)-7: -0.33 points] and increases in PTSD (PCL-6: 0.22 points). Conversely, retrospective symptom analyses demonstrated significant large increases (PHQ-9: 2.40; GAD-7 = 1.97), with 55% reported worsening mental health since the beginning of the pandemic on a global change rating. Across both prospective and retrospective measures of symptom change, worsening depression, anxiety and PTSD symptoms were associated with prior mental health diagnoses, female gender, young age and unemployed/student status. CONCLUSIONS: We highlight the effect of prior mental health diagnoses on worsening mental health during the pandemic and confirm previously reported sociodemographic risk factors. Discrepancies between prospective and retrospective measures of changes in mental health may be related to recall bias-related underestimation of prior symptom severity.

Effectiveness of pulmonary rehabilitation in COVID-19 respiratory failure patients post-ICU.

INTRODUCTION: Some COVID-19 patients develop respiratory failure requiring admission to intensive care unit (ICU). We aim to evaluate the effects of pulmonary rehabilitation (PR) post-ICU in COVID-19 patients. METHODS: Twenty-one COVID-19 patients were evaluated pre- and post-PR and compared retrospectively to a non-COVID-19 group of 21 patients rehabilitated after ICU admission due to respiratory failure. RESULTS: PR induced greater 6-min walking distance improvement in COVID-19 patients (+205 ± 121 m) than in other respiratory failure patients post-ICU (+93 ± 66 m). The sooner PR was performed post-ICU, the better patients recovered. CONCLUSIONS: PR induced large functional improvements in COVID-19 patients post-ICU although significant physical and psychosocial impairments remained post-PR.

Rheumatoid arthritis synovial microenvironment induces metabolic and functional adaptations in dendritic cells.

Rheumatoid arthritis (RA) is a chronic autoimmune disease which causes degradation of cartilage and bone. It is well appreciated that the pathogenic hallmark of RA is the mass influx of inflammatory cells into the joint. However, the role that dendritic cells (DC) may play in this inflammatory milieu is still relatively unexplored. Moreover, the contribution this unique synovial microenvironment has on DC maturation is still unknown. Using monocyte-derived DC (MoDC), we established an in-vitro model to recapitulate the synovial microenvironment to explore DC maturation. MoDC treated with conditioned media from ex-vivo synovial tissue biopsy cultures [explant-conditioned media (ECM)] have increased expression of proinflammatory cytokines, chemokines and adhesion molecules. ECM DC have increased expression of CD83 and CC-chemokine receptor (CCR)7 and decreased expression of CCR5 and phagocytic capacity, suggestive of heightened DC maturation. ECM-induced maturation is concomitant with altered cellular bioenergetics, whereby increased expression of glycolytic genes and increased glucose uptake are observed in ECM DC. Collectively, this results in a metabolic shift in DC metabolism in favour of glycolysis. These adaptations are in-part mediated via signal transducer and activator of transcription-3 (STAT-3), as demonstrated by decreased expression of proinflammatory cytokines and glycolytic genes in ECM DC in response to STAT-3 inhibition. Finally, to translate these data to a more in-vivo clinically relevant setting, RNA-seq was performed on RA synovial fluid and peripheral blood. We identified enhanced expression of a number of glycolytic genes in synovial CD1c+ DC compared to CD1c+ DC in circulation. Collectively, our data suggest that the synovial microenvironment in RA contributes to DC maturation and metabolic reprogramming.

Increased T Cell Plasticity With Dysregulation of Follicular Helper T, Peripheral Helper T, and Treg Cell Responses in Children With Juvenile Idiopathic Arthritis and Down Syndrome-Associated Arthritis.

OBJECTIVE: Juvenile idiopathic arthritis (JIA) is the most common inflammatory arthritis in children; however, an aggressive, erosive arthritis of little-known immunologic mechanism occurs 20 times more frequently in children with Down syndrome. This study was undertaken to characterize T cell and B cell polyreactivity, follicular helper T (Tfh) cell, peripheral helper T (Tph) cell, and Treg cell responses, and synovial inflammation in Down syndrome-associated arthritis (DA). METHODS: Multiparametric flow cytometric analysis and Simplified Presentation of Incredibly Complex Evaluations (SPICE) software were used to examine peripheral blood B cell populations and T cell cytokine responses in patients with DA, JIA, Down syndrome (trisomy 21 [T21]), and in healthy controls. Tfh and Tph cell frequency and origin, in addition to Treg cell frequency, were also evaluated. Synovial inflammation was assessed by immunohistology. RESULTS: Expansion of IgM-only memory B cells was demonstrated in DA compared to JIA (mean ± SEM 22.48 ± 3.278 versus 9.011 ± 1.317; P = 0.005), paralleled by decreased frequency of transitional B cells. T cell responses in DA were characterized by marked functional plasticity, as was evident from the increased frequency of polyfunctional CD8+ Th cells (P < 0.05), CD161+ Th cells (P < 0.05), and CD8- Th cells (P < 0.001), and positivity for tumor necrosis factor, interferon-γ, interleukin-17A, or granulocyte-macrophage colony-stimulating factor, compared to all other groups. Significant expansion of CXCR3+CCR6+ (Th1/Th17) Tfh cells (P = 0.003) and CXCR3+CCR6+ Tph cells (P = 0.01), paralleled by a decrease in CXCR3-CCR6- (Th2) Tfh cells was observed in DA compared to T21. Treg cells were significantly reduced in DA compared to T21 (mean ± SEM 7.111 ± 0.9518 versus 11.96 ± 1.055 versus; P = 0.0028), with a specific reduction in the naive:memory Treg cell ratio. Marked synovial tissue inflammation and increased T cell and B cell infiltrations were demonstrated in DA compared to JIA. CONCLUSION: DA is more common and more aggressive than JIA. It is characterized by increased polyreactive Th, Tfh, and Tph cell responses, reduced Treg cell frequency, and evidence of increased synovial inflammation, all of which are potentially distinct from JIA and T21.

Enhanced angiogenic function in response to fibroblasts from psoriatic arthritis synovium compared to rheumatoid arthritis.

INTRODUCTION: Angiogenesis is an early event in the pathogenesis of both psoriatic arthritis (PsA) and rheumatoid arthritis (RA); however, there are striking differences in blood vessel morphology and activation between the two arthropathies. The aim of this study was to assess if the PsA and RA joint microenvironments differentially regulate endothelial cell function. METHODS: PsA and RA primary synovial fibroblasts (SFC) were isolated from synovial biopsies, grown to confluence, and supernatants harvested and termed 'conditioned media' (CM). Human umbilical vein endothelial cells (HUVEC) were cultured with PsA SFC or RA SFC-CM (20%). HUVEC tube formation, migration, and PBMC adhesion were assessed by matrigel tube formation, wound repair, and PBMC adhesion assays. HUVEC cell surface expression of ICAM, VCAM, and E-Selectin was assessed by flow cytometry. Transcriptome analysis of genes promoting angiogenesis was performed by real-time PCR. Finally, a MSD multiplex angiogenic assay was performed on PsA SFC and RA SFC supernatants. RESULTS: Macroscopic synovitis and vascularity were similar in PsA and RA patients; however, significant differences in vascular morphological pattern were recorded with tortuous, elongated vessels observed in PsA compared to straight regular branching vessels observed in RA. Transcriptome analysis showed strong upregulation of the pro-angiogenic signature in HUVEC primed with PsA SFC-CM compared to RA SFC-CM and basal control. In parallel, paired PsA SFC-CM significantly induced HUVEC tube formation compared to that of RA SFC-CM. Furthermore, PsA SFC-CM induced HUVEC migration was paralleled by a significant induction in VEGFA, PFKFB3, ICAM-1, and MMP3 mRNA expression. A significant increase in PBMC adhesion and cell surface expression of VCAM-1, ICAM-1, and E-Selectin expression was also demonstrated in PsA SFC-CM-primed HUVEC compared to RA SFC-CM. Finally, VEGF, TSLP, Flt-1, and Tie-2 expression was elevated in PsA SFC-CM compared to RA SFC-CM, with no significant difference in other pro-angiogenic mediators including MIP-3, bFGF, PIGF, and MCP-1. CONCLUSION: PsA SFC and RA SFC secreted factors differentially regulate endothelial cell function, with soluble mediators in the PsA joint microenvironment inducing a more pro-angiogenic phenotype compared to the RA.

Time-intensive behavioural activation for depression: A multiple baseline study.

BACKGROUND AND OBJECTIVES: Depression is the second leading cause of disability, worldwide, and increasing access to its effective/preferred treatment requires more attention. Behavioural activation and time-intensive treatment delivery both show promise in this regard, yet research into their combination is limited. This study aimed to investigate the feasibility, effectiveness, and acceptability of time-intensive behavioural activation (BA) for depression METHODS: Eight adults with major depressive disorder were recruited from three outpatient IAPT services in London. The study employed a single case experimental design with multiple baselines. All participants completed time-intensive BA, consisting of up to seven twice weekly sessions with daily prompting in-between and three optional booster sessions. Idiographic, standardised and process measures of depression symptomatology were collected. RESULTS: Treatment recruitment and retention indicated that the intervention was feasible. Visual and statistical analyses showed that relative to baseline, 6 out of 8 participants made significant improvements in all idiographic symptoms of depression following the intervention. According to standardised measures of depression, four out of eight participants were considered treatment responders. Five participants completed follow-up measures and the majority of progress was maintained after the withdrawal of the intervention. The intervention was also considered highly acceptable by participants and therapists. LIMITATIONS: Conclusions cannot be drawn about the generalizability or the long-term durability of the findings CONCLUSIONS: Overall this study provides new, but tentative evidence highlighting the potential of time-intensive BA as a feasible, effective and acceptable treatment for some adult outpatients with depression. The findings now warrant further, more rigorous evaluation of the treatment.

Ankylosing Spondylitis Response to TNF Inhibition Is Gender Specific: A 6-Year Cohort Study

Aim Recent studies have suggested gender-specific differences with respect to both baseline disease activity and severity in ankylosing spondylitis (AS). Tumour necrosis factor inhibitors (TNFi) have shown significant benefit in AS but there may be gender-specific differences regarding responses to TNFi therapy. Methods AS patients with active disease despite adequate trials of NSAIDs were commenced on TNFi and followed in a biologic clinic between 2004 and 2011. Response to treatment was measured based on clinical and serological outcomes. Baseline radiographic data were also collected where available. Results 147 AS patients commenced TNFi therapy and were followed in a biologic clinic between 2004 and 2011. One-hundred and six (72%) of the patients were male and 90 (61%) were current or ex-smokers. The specific TNFi prescribed included etanercept (74 patients, 50.3%), adalimumab (51 patients, 34.7%), infliximab (21 patients, 14.2%) and golimumab (1 patient, 0.7%). The median mSASSS score was 11 (interquartile range 5-35). At baseline, the metrology indices (BASMI) were significantly lower in women (2.6 v 4; p=0.01) but all other clinical indices were similar. At 3 months, female patients had significantly worse median disease activity and functional indices (BASDAI: 4 v 2; p<0.01; BASFI: 3 v 2; p=0.03) than male patients. In addition, females had higher median ESR (19 v 6; p<0.01) which correlated with their disease activity indices (r=0.42, p=0.02). Discussion Despite similar disease activity at baseline, post-TNFi therapy women had significantly higher disease activity. Furthermore, ESR levels in women during therapy correlated with their clinical disease activity scores. Further exploration of these gender-specific differences is crucial for a greater understanding of the pathogenesis of AS as well as development of targeted therapies.

Is current smoking status and its relationship to anti-cyclic citrullinated peptide antibodies a predictor of worse response to biological therapies in rheumatoid arthritis patients?

OBJECTIVE: To assess the association between smoking, anti-cyclic citrullinated peptide (anti-CCP) antibody status, and clinical efficacy of biological therapies in rheumatoid arthritis (RA) patients. METHOD: This retrospective clinical practice setting study included 1349 RA patients from the METEOR database (aged >18 years). We collected data on sociodemographics, smoking status (smoker, <10, 10-19, and >20 cigarettes/day; ex-smoker; non-smoker), baseline disease activity parameters and anti-CCP, previous disease-modifying anti-rheumatic drugs (DMARDs), biological therapy, combined therapy (steroids and DMARDs), and follow-up disease activity. Clinical efficacy was assessed by European League Against Rheumatism (EULAR) good/moderate response rates for all aggregated biological therapies, based on both smoking and anti-CCP status. RESULTS: The non-smoking RA patients were more often female at biological therapy initiation than the ex-smokers and smokers (91.1% vs 60.4% and 67.9%, respectively, p < 0.001), and ex-smokers were older than non-smokers and smokers (mean ± sd 56.5 ± 11.1, 53.5 ± 13.3 and 51.3 ± 11.0 years old, respectively; p < 0.001). In total, 845 (62.6%) were non-smokers, 214 (15.9%) ex-smokers, and 290 (21.5%) smokers [daily cigarettes smoked: 148 (11%) <11; 61 (4.5%) 11-20; and 81 (6%) >20]. Anti CCP-antibody status was similar in both groups. Non-smokers showed higher baseline DAS28 than ex-smokers and smokers (5.0 ± 1.5 vs 4.7 ± 1.4 and 4.7 ± 1.4, respectively; p < 0.001) and used more baseline steroids and DMARDs. A higher EULAR response rate was observed in non-smokers than in ex-smokers and smokers (73% vs 65% and 64.1%, respectively; p = 0.004). Drug survival was higher in non-smokers compared to ex-smokers and smokers [57.7 months (46.4-53.8), 38.6 (30.3-46.8), and 50.1 (41.8-58.4); p < 0.001, respectively]. CONCLUSION: In daily clinical practice, non-smokers respond better than smokers to biological therapy, but this does not result in better drug survival.

Body dysmorphic disorder in patients undergoing septorhinoplasty surgery: should we be performing routine screening?

OBJECTIVE: Body dysmorphic disorder (BDD) is defined as having a preoccupation with a perceived flaw in one's appearance, which appears slight to others and significantly interferes with a person's functioning. When undetected in septorhinoplasty patients, it will often lead to poor outcomes. DESIGN: We performed a prospective cohort study to determine the prevalence of BDD in our patients and whether surgical correction could be considered. SETTING AND PARTICIPANTS: We recruited 34 patients being considered for septorhinoplasty in a tertiary referral rhinology clinic and a control group of 50 from the otology clinic giving a total of 84. MAIN OUTCOME MEASURES: Participants completed the Body Dysmorphic Disorder Questionnaire (BDDQ), the sino-nasal outcome test-23 (SNOT-23) and underwent nasal inspiratory peak flow (NIPF). Those found to be at high risk for BDD were referred to a clinical psychologist. RESULTS: Of the septorhinoplasty patients, 11 (32%) were high risk for BDD. Following psychological assessment, 7 (63%) patients were felt to be unsuitable for surgery and were offered psychological therapy. SNOT-23 scores were significantly higher in the BDD group indicating a negative impact on quality of life. NIPF readings were not significantly different in the BDD group compared to the control group. CONCLUSIONS: The BDDQ is a valid tool for identifying patients at risk of BDD. A close working relationship with clinical psychology has been advantageous to help the selection process of candidates for surgery when there is a high risk of BDD.

Dysregulated bioenergetics: a key regulator of joint inflammation.

OBJECTIVES: This study examines the relationship between synovial hypoxia and cellular bioenergetics with synovial inflammation. METHODS: Primary rheumatoid arthritis synovial fibroblasts (RASF) were cultured with hypoxia, dimethyloxalylglycine (DMOG) or metabolic intermediates. Mitochondrial respiration, mitochondrial DNA mutations, cell invasion, cytokines, glucose and lactate were quantified using specific functional assays. RASF metabolism was assessed by the XF24-Flux Analyzer. Mitochondrial structural morphology was assessed by transmission electron microscopy (TEM). In vivo synovial tissue oxygen (tpO2 mmHg) was measured in patients with inflammatory arthritis (n=42) at arthroscopy, and markers of glycolysis/oxidative phosphorylation (glyceraldehyde 3-phosphate dehydrogenase (GAPDH), PKM2, GLUT1, ATP) were quantified by immunohistology. A subgroup of patients underwent contiguous MRI and positron emission tomography (PET)/CT imaging. RASF and human dermal microvascular endothelial cells (HMVEC) migration/angiogenesis, transcriptional activation (HIF1α, pSTAT3, Notch1-IC) and cytokines were examined in the presence of glycolytic inhibitor 3-(3-Pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO). RESULTS: DMOG significantly increased mtDNA mutations, mitochondrial membrane potential, mitochondrial mass, reactive oxygen species and glycolytic RASF activity with concomitant attenuation of mitochondrial respiration and ATP activity (all p<0.01). This was coupled with altered mitochondrial morphology. Hypoxia-induced lactate levels (p<0.01), which in turn induced basic fibroblast growth factor (bFGF) secretion and RASF invasiveness (all p<0.05). In vivo glycolytic markers were inversely associated with synovial tpO2 levels <20 mm Hg, in contrast ATP was significantly reduced (all p<0.05). Decrease in GAPDH and GLUT1 was paralleled by an increase in in vivo tpO2 in tumour necrosis factor alpha inhibitor (TNFi) responders. Novel PET/MRI hybrid imaging demonstrated close association between metabolic activity and inflammation. 3PO significantly inhibited RASF invasion/migration, angiogenic tube formation, secretion of proinflammatory mediators (all p<0.05), and activation of HIF1α, pSTAT3 and Notch-1IC under normoxic and hypoxic conditions. CONCLUSIONS: Hypoxia alters cellular bioenergetics by inducing mitochondrial dysfunction and promoting a switch to glycolysis, supporting abnormal angiogenesis, cellular invasion and pannus formation.

European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update.

BACKGROUND: Since the publication of the European League Against Rheumatism recommendations for the pharmacological treatment of psoriatic arthritis (PsA) in 2012, new evidence and new therapeutic agents have emerged. The objective was to update these recommendations. METHODS: A systematic literature review was performed regarding pharmacological treatment in PsA. Subsequently, recommendations were formulated based on the evidence and the expert opinion of the 34 Task Force members. Levels of evidence and strengths of recommendations were allocated. RESULTS: The updated recommendations comprise 5 overarching principles and 10 recommendations, covering pharmacological therapies for PsA from non-steroidal anti-inflammatory drugs (NSAIDs), to conventional synthetic (csDMARD) and biological (bDMARD) disease-modifying antirheumatic drugs, whatever their mode of action, taking articular and extra-articular manifestations of PsA into account, but focusing on musculoskeletal involvement. The overarching principles address the need for shared decision-making and treatment objectives. The recommendations address csDMARDs as an initial therapy after failure of NSAIDs and local therapy for active disease, followed, if necessary, by a bDMARD or a targeted synthetic DMARD (tsDMARD). The first bDMARD would usually be a tumour necrosis factor (TNF) inhibitor. bDMARDs targeting interleukin (IL)12/23 (ustekinumab) or IL-17 pathways (secukinumab) may be used in patients for whom TNF inhibitors are inappropriate and a tsDMARD such as a phosphodiesterase 4-inhibitor (apremilast) if bDMARDs are inappropriate. If the first bDMARD strategy fails, any other bDMARD or tsDMARD may be used. CONCLUSIONS: These recommendations provide stakeholders with an updated consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes in PsA, based on a combination of evidence and expert opinion.

The classification of Obsessive-Compulsive and Related Disorders in the ICD-11.

BACKGROUND: To present the rationale for the new Obsessive-Compulsive and Related Disorders (OCRD) grouping in the Mental and Behavioural Disorders chapter of the Eleventh Revision of the World Health Organization's International Classification of Diseases and Related Health Problems (ICD-11), including the conceptualization and essential features of disorders in this grouping. METHODS: Review of the recommendations of the ICD-11 Working Group on the Classification for OCRD. These sought to maximize clinical utility, global applicability, and scientific validity. RESULTS: The rationale for the grouping is based on common clinical features of included disorders including repetitive unwanted thoughts and associated behaviours, and is supported by emerging evidence from imaging, neurochemical, and genetic studies. The proposed grouping includes obsessive-compulsive disorder, body dysmorphic disorder, hypochondriasis, olfactory reference disorder, and hoarding disorder. Body-focused repetitive behaviour disorders, including trichotillomania and excoriation disorder are also included. Tourette disorder, a neurological disorder in ICD-11, and personality disorder with anankastic features, a personality disorder in ICD-11, are recommended for cross-referencing. LIMITATIONS: Alternative nosological conceptualizations have been described in the literature and have some merit and empirical basis. Further work is needed to determine whether the proposed ICD-11 OCRD grouping and diagnostic guidelines are mostly likely to achieve the goals of maximizing clinical utility and global applicability. CONCLUSION: It is anticipated that creation of an OCRD grouping will contribute to accurate identification and appropriate treatment of affected patients as well as research efforts aimed at improving our understanding of the prevalence, assessment, and management of its constituent disorders.

[COLIBRI: Improving clinical practice and producing relevant scientific data]. / COLIBRI : optimiser la pratique clinique et produire des données scientifiques pertinentes.

COLIBRI-COPD is a francophone consultation web portal accessible to pulmonologists in the hospital and in the community. We present this observation which describes the phenotype of COPD patients entered (anthropometry, exposures, addictions, functional impairments, questionnaires: MRC, DIRECT, CAT, HAD, Epworth, co-morbidities, incidence of exacerbations, drug treatment or other treatments). The results of the first 1079 patients show a high level of completeness for the main data items. A comparison of patients seen in outpatient consultations shows significant variability between patients with the same GOLD stage, regarding the incidence of exacerbations, signs of anxiety-depression, of diabetes mellitus, or the prescriptions of anticholinergics and inhaled corticosteroids. These initial results suggest that data collection in real life gives a reliable database to obtain longitudinal data on various aspects of COPD. The data quality (completeness, reliability) is partly related to the usability of the web tool and to the possibility of doing self-assessment of practitioners' own recorded data.

Tofacitinib regulates synovial inflammation in psoriatic arthritis, inhibiting STAT activation and induction of negative feedback inhibitors.

BACKGROUND: Psoriatic arthritis (PsA) is a chronic inflammatory disease, characterised by synovitis and destruction of articular cartilage/bone. Janus-kinase and signal transducer and activator of transcription (JAK-STAT) signalling pathway is implicated in the pathogenesis of PsA. OBJECTIVES: To examine the effect of tofacitinib (JAK inhibitor) on proinflammatory mechanisms in PsA. METHODS: Primary PsA synovial fibroblasts (PsAFLS) and ex vivo PsA synovial explants were cultured with tofacitinib (1 µM). PhosphoSTAT3 (pSTAT3), phosphoSTAT1 (pSTAT1), suppressor of cytokine signaling-3 (SOCS3), protein inhibitor of activated Stat3 (PIAS3) and nuclear factor kappa B cells (NFκBp65) were quantified by western blot. The effect of tofacitinib on PsAFLS migration, invasion, Matrigel network formation and matrix metallopeptidase (MMP)2/9 was quantified by invasion/migration assays and zymography. Interleukin (IL)-6, IL-8, IFN-gamma-inducible protein 10 (IP-10) monocyte chemoattractant protein (MCP)-1, IL-17, IL-10, MMP3 and tissue inhibitor of metalloproteinases 3 (TIMP3) were assessed by ELISA. RESULTS: Tofacitinib significantly decreased pSTAT3, pSTAT1, NFκBp65 and induced SOCS3 and PIAS3 expression in PsAFLS and synovial explant cultures (p<0.05). Functionally, PsAFLS invasion, network formation and migration were inhibited by tofacitinib (all p<0.05). In PsA explant, tofacitinib significantly decreased spontaneous secretion of IL-6, IL-8, MCP-1, MMP9/MMP2, MMP3 (all p<0.05) and decreased the MMP3/TIMP3 ratio (p<0.05), with no effect observed for IP-10 or IL-10. CONCLUSIONS: This study further supports JAK-STAT inhibition as a therapeutic target for the treatment of PsA.

Biomarkers for rheumatoid and psoriatic arthritis.

Rheumatic diseases, such as rheumatoid and psoriatic arthritis are systemic inflammatory conditions characterized by a chronic form of arthritis, often leading to irreversible joint damage. Early treatment for patients with rheumatic diseases is required to reduce or prevent joint injury. However, early diagnosis can be difficult and currently it is not possible to predict which individual patient will develop progressive erosive disease or who may benefit from a specific treatment according to their clinical features at presentation. Biomarkers are therefore required to enable earlier diagnosis and predict prognosis in both rheumatoid arthritis and psoriatic arthritis. In this review we will examine the evidence and current status of established and experimental biomarkers in rheumatoid and psoriatic arthritis for three important purposes; disease diagnosis, prognosis and prediction of response to therapy.

Psychological characteristics and motivation of women seeking labiaplasty.

BACKGROUND: Labiaplasty is an increasingly popular surgical intervention but little is known about the characteristics and motivation of women who seek the procedure or the psychosexual outcome. METHOD: A total of 55 women seeking labiaplasty were compared with 70 women who did not desire labiaplasty. Various general measures of psychopathology as well as specific measures (Genital Appearance Satisfaction; Cosmetic Procedure Screening for labiaplasty) were used. Labia measurements of the women seeking labiaplasty were also obtained. RESULTS: Women seeking labiaplasty did not differ from controls on measures of depression or anxiety. They did, however, express increased dissatisfaction towards the appearance of their genitalia, with lower overall sexual satisfaction and a poorer quality of life in terms of body image. Women seeking labiaplasty reported a significantly greater frequency of avoidance behaviours on all the domains assessed, and greater frequency of safety-seeking behaviours for most of the domains. Key motivations reported for labiaplasty were categorized as cosmetic, functional or sexual. Of the 55 women seeking labiaplasty, 10 met diagnostic criteria for body dysmorphic disorder. CONCLUSIONS: This is the first controlled study to describe some of the characteristics and motivations of women seeking labiaplasty. We identified a wide range of avoidance and safety-seeking behaviours, which occurred more frequently in the labiaplasty group than the control group. These could be used clinically as part of a psychological intervention for women seeking labiaplasty.

Toxicovigilance. I: A survey of acute poisonings in South Africa based on Tygerberg Poison Information Centre data.

BACKGROUND: The incidence and spectrum of acute poisonings in South Africa are unknown. Poisoning data can be derived from sources such as hospital admission records and poison information centre (PIC) records. OBJECTIVES: This study was conducted to examine the extent of the problem and to identify trends and toxicovigilance issues using PIC data. METHODS: A survey was conducted based on Tygerberg Poison Information Centre (TPIC) consultations over 1 year. TPIC consultation forms were analysed for patient demographics and causes of poisoning. RESULTS: The TPIC dealt with 4 771 consultations related to human exposures to poisonous substances. The study showed that accidental exposure was more common than intentional poisoning (65.2% v. 34.8%); that 55.8% of cases were adults, of which 57.6% were females; and that 61.4% of adult cases were intentional exposures, and of these 64.3% were females. There was a predominance of accidental exposures (98.8%) and a male predominance (59.7%) in children. Categories of poisoning exposures across all age groups were non-drug chemicals (52.7%), medicines (35.2%) and biological toxins (12.6%). Pesticides (34.8%), irritant/corrosive substances (27.7%) and volatile hydrocarbons (8.3%) were the most common classes of non-drug chemical exposures. Cholinesterase inhibitors (8.8%), anticoagulant rodenticides (7.1%) and pyrethroids (5.0%) were the most commonly ingested non-drug chemicals. Aldicarb and amitraz poisoning were identified as toxicovigilance targets. Analgesics (26.1%) were the most common class of medicine-related exposure, and paracetamol (15.8%), benzodiazepines (9.2%) and antihistamines (5.2%) were the most common medicine-related exposures. CONCLUSION: The study provided information on evolving trends and identified toxicovigilance targets and the need for continuing toxicology education programmes.

Toxicovigilance. II: A survey of the spectrum of acute poisoning and current practices in the initial management of poisoning cases admitted to South African hospitals.

BACKGROUND: Initial management of acute poisoning in South African (SA) hospitals such as gastric decontamination and use of antidotes has not been evaluated relevant to current international guidelines. OBJECTIVES: The objective of this study was to conduct a toxicovigilance survey of SA hospital admissions to assess the spectrum of acute poisonings, current practices in gastric decontamination, and use of antidotes in the management of acute poisoning. METHODS: A survey was undertaken based on acute poisoning admissions to Tygerberg Academic Hospital (TAH) as well as hospital-based poisoning consultations with the Tygerberg Poison Information Centre (TPIC) over 1 year to investigate trends in admissions and the initial management of hospital admissions for acute poisoning. TAH admission details and TPIC consultation forms for hospital-based cases were analysed for patient demographics, causes of poisoning, gastric decontamination measures and use of antidotes. RESULTS: There were 662 admissions to TAH and 2 459 hospital-based TPIC consultations. Paracetamol and cholinesterase inhibitors were the most common exposures in both studies. Gastric decontamination measures were employed at TAH in 47.7% of cases and in 5.3% of hospital cases reported to the TPIC. Of these, 67.4% in the TAH study and 26.1% in the TPIC study did not comply with international guidelines. N-acetylcysteine was administered inappropriately in 22.1% of the paracetamol poisoning cases at TAH and in 1.6% in the TPIC study. Atropine was administered unnecessarily in 12 of 30 TPIC cases. CONCLUSION: This study has identified the need for directed training on gastric decontamination measures and use of antidotes and, combined with the previous study, has identified national trends in poisoning.