Treating common mental disorder including psychotic experiences in the primary care improving access to psychological therapies programme (the TYPPEX study): protocol for a stepped wedge cluster randomised controlled trial with nested economic and process evaluation of a training package for therapists.

INTRODUCTION: At least one in four people treated by the primary care improving access to psychological therapies (IAPT) programme in England experiences distressing psychotic experiences (PE) in addition to common mental disorder (CMD). These individuals are less likely to achieve recovery. IAPT services do not routinely screen for nor offer specific treatments for CMD including PE. The Tailoring evidence-based psychological therapY for People with common mental disorder including Psychotic EXperiences study will evaluate the clinical and cost-effectiveness of an enhanced training for cognitive behavioural therapists that aims to address this clinical gap. METHODS AND ANALYSIS: This is a multisite, stepped-wedge cluster randomised controlled trial. The setting will be IAPT services within three mental health trusts. The participants will be (1) 56-80 qualified IAPT cognitive behavioural therapists and (2) 600 service users who are triaged as appropriate for cognitive behavioural therapy in an IAPT service and have PE according to the Community Assessment of Psychic Experiences-Positive 15-items Scale. IAPT therapists will be grouped into eight study clusters subsequently randomised to the control-intervention sequence. We will obtain pseudonymous clinical outcome data from IAPT clinical records for eligible service users. We will invite service users to complete health economic measures at baseline, 3, 6, 9 and 12-month follow-up. The primary outcome will be the proportion of patients with common mental disorder psychotic experiences who have recovered by the end of treatment as measured by the official IAPT measure for recovery. ETHICS AND DISSEMINATION: The study received the following approvals: South Central-Berkshire Research Ethics Committee on 28 April 2020 (REC reference 20/SC/0135) and Health Research Authority (HRA) on 23 June 2020. An amendment was approved by the Ethics Committee on 01 October 2020 and HRA on 27 October 2020. Results will be made available to patients and the public, the funders, stakeholders in the IAPT services and other researchers. TRIAL REGISTRATION NUMBER: ISRCTN93895792.

Autism Spectrum Disorder in Early Intervention in Psychosis Services: Implementation and Findings of a 3-step Screening and Diagnostic Protocol.

Evidence indicates that autism spectrum disorder (ASD) is underidentified in populations with psychosis, but that clinical presentations of comorbid ASD and psychosis (ASD-P) and specific treatment needs that may relate to this group are not well understood. In fact, recent studies of ASD in first-episode psychosis suggest that there may be a specific clinical presentation of ASD-P. In response, the Cambridgeshire and Peterborough Early Intervention in Psychosis (EIP) service in the UK implemented and evaluated a 3-step ASD screening and diagnostic protocol, using the Autism Spectrum Disorder in Adults Screening Questionnaire (ASDASQ), case note review, and the Autism Diagnostic Observation Schedule (ADOS-2) and the Childhood Autism Spectrum Test (CAST). As a quality improvement project, the evaluation aimed to (1) establish the prevalence of patients with ASD-P, (2) describe characteristics of the clinical presentation of ASD-P and compare them to those of patients suffering from psychosis but no ASD, and (3) determine any differences in treatment between psychosis patients with and without ASD. Notably, at least 9% of the EIP service caseload met the criteria for a diagnosis of ASD-P, with half identified via the implementation of this protocol. The patients with ASD-P had specific clinical presentations and treatment needs that differed from those of patients with psychosis but no ASD. Thus, the findings from this study supported existing evidence concerning the underdetection of ASD in EIP populations. Our findings also added to emerging evidence for a clinical presentation of ASD-P with specific treatment needs. Our protocol has now been established as routine practice, and its implementation has improved the detection and treatment of patients with ASD-P within our EIP service.

Baseline serum MMP-3 levels in patients with Rheumatoid Arthritis are still independently predictive of radiographic progression in a longitudinal observational cohort at 8 years follow up.

INTRODUCTION: At present, there is no reliable tool for predicting disease outcome in patients with rheumatoid arthritis (RA). We previously demonstrated an association between specific baseline biomarkers/clinical measures including matrix metalloproteinase-3 (MMP-3) and 2-year radiographic progression in patients with RA. This study further evaluates the predictive capability of these baseline variables with outcome extended over 8-years. METHODS: Fifty-eight of the original cohort (n = 118) had radiographic progression from baseline to mean 8.2-years determined using the van der Heijde modified Sharp method. The contribution of each predictor variable towards radiographic progression was assessed with univariate and multivariate analyses. RESULTS: Traditional factors (including erythrocyte sedimentation rate, C-reactive protein, anti-cyclic citrullinated peptide (anti-CCP), and rheumatoid factor) and biomarkers of tissue destruction (including MMP-3, C-telopeptide of type II collagen, cartilage oligomeric matrix protein, and tissue inhibitor of metalloproteinase 1) measured at baseline were associated with radiographic progression at endpoint. Multivariate logistic regression identified anti-CCP seropositivity [OR 9.29, 95%CI: 2.29-37.64], baseline elevated MMP-3 [OR 8.25, 95%CI: 2.54-26.78] and baseline radiographic damage [OR 5.83, 95%CI: 1.88-18.10] as the strongest independent predictors of radiographic progression. A model incorporating these variables had a predictive accuracy of 0.87, assessed using the area under the receiver operating characteristic curve. CONCLUSION: In our cohort with onset of RA symptoms < 2-years, multivariate analysis identified anti-CCP status and baseline MMP-3 as the strongest independent predictors of radiographic disease outcome at 8.2-years. This finding suggests determination of baseline MMP-3, in conjunction with traditional serologic markers, may provide additional prognostic information for patients with RA. Furthermore, these findings highlight the importance of continued research into a broad range of biomarkers as potential predictors of joint damage.

A randomized, double-blind, controlled study of ultrasound-guided corticosteroid injection into the joint of patients with inflammatory arthritis.

OBJECTIVE: Most corticosteroid injections into the joint are guided by the clinical examination (CE), but up to 70% are inaccurately placed, which may contribute to an inadequate response. The aim of this study was to investigate whether ultrasound (US) guidance improves the accuracy and clinical outcome of joint injections as compared with CE guidance in patients with inflammatory arthritis. METHODS: A total of 184 patients with inflammatory arthritis and an inflamed joint (shoulder, elbow, wrist, knee, or ankle) were randomized to receive either US-guided or CE-guided corticosteroid injections. Visual analog scales (VAS) for assessment of function, pain, and stiffness of the target joint, a modified Health Assessment Questionnaire, and the EuroQol 5-domain questionnaire were obtained at baseline and at 2 weeks and 6 weeks postinjection. The erythrocyte sedimentation rate and C-reactive protein level were measured at baseline and 2 weeks. Contrast injected with the steroid was used to assess the accuracy of the joint injection. RESULTS: One-third of CE-guided injections were inaccurate. US-guided injections performed by a trainee rheumatologist were more accurate than the CE-guided injections performed by more senior rheumatologists (83% versus 66%; P = 0.010). There was no significant difference in clinical outcome between the group receiving US-guided injections and the group receiving CE-guided injections. Accurate injections led to greater improvement in joint function, as determined by VAS scores, at 6 weeks, as compared with inaccurate injections (30.6 mm versus 21.2 mm; P = 0.030). Clinicians who used US guidance reliably assessed the accuracy of joint injection (P < 0.001), whereas those who used CE guidance did not (P = 0.29). CONCLUSION: US guidance significantly improves the accuracy of joint injection, allowing a trainee to rapidly achieve higher accuracy than more experienced rheumatologists. US guidance did not improve the short-term outcome of joint injection.

Biomarkers predict radiographic progression in early rheumatoid arthritis and perform well compared with traditional markers.

OBJECTIVE: To evaluate the performance of biochemical and traditional markers in predicting radiographic progression in rheumatoid arthritis (RA). METHODS: One hundred thirty-two patients with early RA were treated with nonbiologic therapies for 2 years and studied longitudinally. Genomic DNA was analyzed for presence of the shared epitope. Levels of matrix metalloproteinases (matrix metalloproteinase 1 [MMP-1], MMP-13, and MMP-3), tissue inhibitor of metalloproteinases 1 (TIMP-1), and cartilage oligomeric matrix protein (COMP) were assessed in serially obtained serum samples. The presence of pyridinoline (Pyr), deoxypyridinoline, glycosylated Pyr (Glc-Gal-Pyr), and C-telopeptide of type II collagen (CTX-II) was assessed in urine samples. Radiographs obtained at entry and at 2 years were evaluated using the modified Larsen score. RESULTS: Baseline and 2-year radiographs were available from 118 patients. Larsen scores worsened during the 2 years in 50 patients, while 68 patients had no radiographic progression. Levels of a variety of biochemical markers, i.e., MMP-3, CTX-II, COMP, TIMP-1, Pyr, and Glc-Gal-Pyr, correlated significantly with radiographic progression at entry and longitudinally as assessed by area under the curve (AUC). By multivariate analysis, a model including MMP-3 and CTX-II was identified as providing the best prediction of radiographic progression at entry (predictive accuracy by receiver operating characteristic [ROC] AUC = 0.76 [95% confidence interval 0.66-0.85]), while a combination of MMP-3, CTX-II, and swollen joint count formed the best longitudinal AUC model (predictive accuracy by ROC AUC = 0.81 [95% confidence interval 0.73-0.89]). Patient-reported measures (Health Assessment Questionnaire, pain scores) were of limited use. In a subset of 50 patients who were treated with methotrexate (MTX) during the followup period, median serum MMP-3 levels decreased after the initiation of MTX therapy (P = 0.0003). CONCLUSION: These results indicate that biochemical markers are useful predictors of radiographic progression in RA and that serum MMP-3 levels decrease significantly with MTX therapy. Multivariate models that include MMP-3 and CTX-II perform better than existing traditional markers in predicting radiographic outcome in RA.

Causes of death in patients with rheumatoid arthritis: comparison with siblings and matched osteoarthritis controls.

OBJECTIVE: Survival of patients with rheumatoid arthritis (RA) is reduced when compared to the general population. We assessed differences in causes and age of death between patients with RA and their siblings. Comparisons were also made with a control group of subjects with lower limb osteoarthritis (OA). METHODS: A population of 257 patients with RA studied in 1991 was compared to 371 of their same-sex siblings and 485 patients with hip and knee OA who were also attending the department at this time. Death certificates were obtained and compared. RESULTS: Among patients with RA, 54% (139/257) were deceased, compared to 28% (105/371) of the siblings and 32% (154/485) of OA patients (RA vs siblings or OA, p < 0.05). There were more deaths due to ischemic heart disease (IHD) in both the RA and OA groups compared to those expected; ratio observed/expected, 1.66 (95% CI 1.01, 2.79) and 1.96 (95% CI 1.21, 3.25), respectively, but not for siblings: observed/expected = 1.05 (95% CI 0.53, 2.08). There was a significant deficit in cancer related deaths in RA patients, observed/expected = 0.62 (95% CI 0.36, 1.03). CONCLUSION: Significantly more patients with RA had died than in either of the comparator populations. RA and OA patients died more frequently of IHD than the siblings. The RA population had a 40% reduced rate of cancer related deaths than expected and compared to their siblings.

Outcome in adults with juvenile idiopathic arthritis: a quality of life study.

OBJECTIVE: To evaluate quality of life (QOL) in adults with juvenile idiopathic arthritis (JIA), using validated measures of functional disability and generic health status, and to quantify their educational attainment and employment status. METHODS: The adult rheumatology departmental database was used to identify patients. Functional disability and generic health status/QOL were assessed by the Health Assessment Questionnaire (HAQ) and the Short Form 36-item health profile (SF-36), respectively. Educational achievement and employment status were assessed by questionnaire. RESULTS: Complete data were available for 82 of the 101 patients identified. The median age of patients was 30 years, and the median disease duration was 21 years. No deaths were recorded. All subtypes of JIA were represented. Thirty-nine percent of patients had active disease (based on the physician global assessment scale score). The median HAQ score was 1.125 (range 0-3). SF-36 scores for bodily pain, general health, physical functioning, vitality, emotion, and social isolation were significantly worse in patients compared with controls, and this trend increased with increasing age of the patients and disease duration. The SF-36 mental summation scores of patients were low compared with those of controls, for all subtypes of JIA, and this finding was independent of the degree of functional disability (by HAQ and SF-36 physical summation scores). The educational attainment of patients was comparable to that of local controls, but unemployment rates for patients were 3-fold higher than those for controls. CONCLUSION: This is the largest study in which the SF-36 was used to assess generic health status and QOL in adults with JIA. Many patients had active disease in adulthood, and although the physical outcome of adults with JIA is relatively good, a profound effect on generic health status and QOL was demonstrated for all types of JIA. Furthermore, despite excellent educational attainment, there was a high rate of unemployment among patients.