Discordance between the predictors of clinical and imaging remission in patients with early rheumatoid arthritis in clinical practice: implications for the use of ultrasound within a treatment to target strategy

Objective: To assess the prevalence, relationship between and predictors of clinical and imaging remission in early rheumatoid arthritis (RA), achieved with treat-to-target management in clinical practice. Methods: A prospective observational study was conducted in patients with new-onset RA. The treatment target was remission by disease activity score (DAS28-CRP<2.6). Twelve month outcomes included DAS28-CRP remission, DAS44-CRP remission, ACR/EULAR Boolean remission (BR) and absent or absent/minimal power Doppler activity (PDA) on ultrasound (US) of 26 joints (total PDA score=0 or ≤1, respectively). Logistic regression was conducted to identify baseline predictors of these outcomes. Results: Of 105 patients with complete 12-month data, the rate of DAS28-CRP remission was 43%, DAS44-CRP remission was 39%, BR was 14%, absent PDA was 40% and absent/minimal PDA was 57%. Amongst patients achieving clinical remission defined by DAS28-CRP, DAS44-CRP or BR, absence of PDA was observed in 42%, 44% and 40%, respectively; absent/minimal PDA was detected in 62%, 66% and 67%, respectively. On multivariable analysis, shorter symptom duration, male gender, fewer tender joints and lower disability were associated with the clinical remission definitions. Lack of osteoarthritis predicted absence of PDA and lower total baseline PDA predicted absent/minimal PDA. Conclusion: DAS28-CRP remission and absence of PDA were observed in almost half of patients, but less than a quarter achieved both. Achievement of BR was rare. The low agreement between any of the clinical and imaging outcomes and differences in their predictors highlight the complex interaction between symptoms and synovitis, with implications for treat-to-target management. Long-term follow-up should determine the most appropriate target

Case formulation—A vehicle for change? Exploring the impact of cognitive behavioural therapy formulation in first episode psychosis: A reflexive thematic analysis

Objectives: Formulation is considered a fundamental process of cognitive behavioural therapy for psychosis (CBTp). However, an exploration into the personal impact of different levels of case formulation (CF) from a service user perspective (SU) is lacking, particularly for those experiencing a first episode of psychosis. Design: This Big Q qualitative design used semi-structured interviews. Methods: Reflexive thematic analysis (TA) was used to analyse 10 participant interviews. NVivo 12 computer-assisted qualitative data analysis software aided data organisation and analysis. Results: One overarching theme ‘CF – A vehicle for change?’ was developed as a pattern of shared meaning across the data set. Three main themes related to the overarching theme: (1) Vicious cycles: ‘I never really thought about it being me maintaining the problems’ (including one subtheme – Self-empowerment: ‘Only you can make the changes for yourself’); (2) Early life experiences: ‘My experiences have shaped the person that I am, therefore, it's not my fault’ (including one subtheme – Disempowerment: ‘[My] core beliefs have been damaged’); and (3) Keep it simple: ‘Don't push it too far over the top in case it becomes like spaghetti’. Conclusions: Maintenance formulations may be experienced as self-blaming, but also self-empowering, which may help to facilitate change. Longitudinal formulations may be experienced as non-blaming, but also disempowering, which may inhibit change. Simple CF diagrams may also facilitate change, whereas overly complex CFs may inhibit change. How CBTp therapists might look to improve the impact of different levels of CF for service users (SUs) in first episode psychosis (FEP) are described

Brief report:effects of sensory sensitivity and intolerance of uncertainty on anxiety in mothers of children with autism spectrum disorder

This study examined the relations between anxiety and individual characteristics of sensory sensitivity (SS) and intolerance of uncertainty (IU) in mothers of children with ASD. The mothers of 50 children completed the Hospital Anxiety and Depression Scale, the Highly Sensitive Person Scale and the IU Scale. Anxiety was associated with both SS and IU and IU was also associated with SS. Mediation analyses showed direct effects between anxiety and both IU and SS but a significant indirect effect was found only in the model in which IU mediated between SS. This is the first study to characterize the nature of the IU and SS interrelation in predicting levels of anxiety

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Genome-wide Association Study of Response to Methotrexate in Early Rheumatoid Arthritis Patients

Methotrexate (MTX) monotherapy is a common first treatment for rheumatoid arthritis (RA), but many patients do not respond adequately. In order to identify genetic predictors of response, we have combined data from two consortia to carry out a genome-wide study of response to MTX in 1424 early RA patients of European ancestry. Clinical endpoints were change from baseline to 6 months after starting treatment in swollen 28-joint count, tender 28-joint count, C-reactive protein and the overall 3-component disease activity score (DAS28). No single nucleotide polymorphism (SNP) reached genome-wide statistical significance for any outcome measure. The strongest evidence for association was with rs168201 in NRG3 (p = 10‾⁷ for change in DAS28). Some support was also seen for association with ZMIZ1, previously highlighted in a study of response to MTX in juvenile idiopathic arthritis. Follow-up in two smaller cohorts of 429 and 177 RA patients did not support these findings, although these cohorts were more heterogeneous

Exploring UK medical school differences: the MedDifs study of selection, teaching, student and F1 perceptions, postgraduate outcomes and fitness to practise.

BACKGROUND: Medical schools differ, particularly in their teaching, but it is unclear whether such differences matter, although influential claims are often made. The Medical School Differences (MedDifs) study brings together a wide range of measures of UK medical schools, including postgraduate performance, fitness to practise issues, specialty choice, preparedness, satisfaction, teaching styles, entry criteria and institutional factors. METHOD: Aggregated data were collected for 50 measures across 29 UK medical schools. Data include institutional history (e.g. rate of production of hospital and GP specialists in the past), curricular influences (e.g. PBL schools, spend per student, staff-student ratio), selection measures (e.g. entry grades), teaching and assessment (e.g. traditional vs PBL, specialty teaching, self-regulated learning), student satisfaction, Foundation selection scores, Foundation satisfaction, postgraduate examination performance and fitness to practise (postgraduate progression, GMC sanctions). Six specialties (General Practice, Psychiatry, Anaesthetics, Obstetrics and Gynaecology, Internal Medicine, Surgery) were examined in more detail. RESULTS: Medical school differences are stable across time (median alpha = 0.835). The 50 measures were highly correlated, 395 (32.2%) of 1225 correlations being significant with p < 0.05, and 201 (16.4%) reached a Tukey-adjusted criterion of p < 0.0025. Problem-based learning (PBL) schools differ on many measures, including lower performance on postgraduate assessments. While these are in part explained by lower entry grades, a surprising finding is that schools such as PBL schools which reported greater student satisfaction with feedback also showed lower performance at postgraduate examinations. More medical school teaching of psychiatry, surgery and anaesthetics did not result in more specialist trainees. Schools that taught more general practice did have more graduates entering GP training, but those graduates performed less well in MRCGP examinations, the negative correlation resulting from numbers of GP trainees and exam outcomes being affected both by non-traditional teaching and by greater historical production of GPs. Postgraduate exam outcomes were also higher in schools with more self-regulated learning, but lower in larger medical schools. A path model for 29 measures found a complex causal nexus, most measures causing or being caused by other measures. Postgraduate exam performance was influenced by earlier attainment, at entry to Foundation and entry to medical school (the so-called academic backbone), and by self-regulated learning. Foundation measures of satisfaction, including preparedness, had no subsequent influence on outcomes. Fitness to practise issues were more frequent in schools producing more male graduates and more GPs. CONCLUSIONS: Medical schools differ in large numbers of ways that are causally interconnected. Differences between schools in postgraduate examination performance, training problems and GMC sanctions have important implications for the quality of patient care and patient safety

The Analysis of Teaching of Medical Schools (AToMS) survey: an analysis of 47,258 timetabled teaching events in 25 UK medical schools relating to timing, duration, teaching formats, teaching content, and problem-based learning.

BACKGROUND: What subjects UK medical schools teach, what ways they teach subjects, and how much they teach those subjects is unclear. Whether teaching differences matter is a separate, important question. This study provides a detailed picture of timetabled undergraduate teaching activity at 25 UK medical schools, particularly in relation to problem-based learning (PBL). METHOD: The Analysis of Teaching of Medical Schools (AToMS) survey used detailed timetables provided by 25 schools with standard 5-year courses. Timetabled teaching events were coded in terms of course year, duration, teaching format, and teaching content. Ten schools used PBL. Teaching times from timetables were validated against two other studies that had assessed GP teaching and lecture, seminar, and tutorial times. RESULTS: A total of 47,258 timetabled teaching events in the academic year 2014/2015 were analysed, including SSCs (student-selected components) and elective studies. A typical UK medical student receives 3960 timetabled hours of teaching during their 5-year course. There was a clear difference between the initial 2 years which mostly contained basic medical science content and the later 3 years which mostly consisted of clinical teaching, although some clinical teaching occurs in the first 2 years. Medical schools differed in duration, format, and content of teaching. Two main factors underlay most of the variation between schools, Traditional vs PBL teaching and Structured vs Unstructured teaching. A curriculum map comparing medical schools was constructed using those factors. PBL schools differed on a number of measures, having more PBL teaching time, fewer lectures, more GP teaching, less surgery, less formal teaching of basic science, and more sessions with unspecified content. DISCUSSION: UK medical schools differ in both format and content of teaching. PBL and non-PBL schools clearly differ, albeit with substantial variation within groups, and overlap in the middle. The important question of whether differences in teaching matter in terms of outcomes is analysed in a companion study (MedDifs) which examines how teaching differences relate to university infrastructure, entry requirements, student perceptions, and outcomes in Foundation Programme and postgraduate training

A potentiated startle study of uncertainty and contextual anxiety in adolescents diagnosed with autism spectrum disorder

Abstract Background Beyond the core symptoms of autism spectrum disorder (ASD), associated symptoms of anxiety can cause substantial impairment for individuals affected by ASD and those who care for them. Methods We utilized a potentiated startle paradigm with a puff of air to the neck as the unconditioned stimulus in order to investigate differences between response to cued fear and contextual anxiety among cognitively able adolescents diagnosed with ASD and an age- and IQ-matched typically developing group. Results In a threat-modulated startle paradigm, response patterns to neutral, predictable, and unpredictable conditions were comparable across typically developing and ASD youth in terms of startle response magnitude and latency. However, the ASD group showed significantly greater absolute startle responsivity at baseline and throughout the experiment, suggesting possibly enhanced general sensitivity to threatening contexts. The ASD group, but not the control group, demonstrated moderate to strong negative correlations between psychophysiological response to unpredictable threats (uncertainty) and questionnaire measures of generalized anxiety, intolerance of uncertainty, and repetitive behavior. Conclusions Our data suggest enhanced general reactivity among the ASD group, possibly reflecting greater sensitivity to the threatening context of the startle paradigm. Associations with the response to uncertainty may help explain shared neurobehavioral mechanisms in ASD and anxiety. This task can provide useful targets for future neuroimaging and genetics studies as well as specific avenues for intervention. We emphasize the importance of further basic and clinical research into links among these important constructs