Lewis Carpenter

The size, burden and cost of disorders of the brain in the UK

Aim: The aim of this paper is to increase awareness of the prevalence and cost of psychiatric and neurological disorders (brain disorders) in the UK. Method: UK data for 18 brain disorders were extracted from a systematic review of European epidemiological data and prevalence rates and the costs of each disorder were summarized (2010 values). Results: There were approximately 45 million cases of brain disorders in the UK, with a cost of €134 billion per annum. The most prevalent were headache, anxiety disorders, sleep disorders, mood disorders and somatoform disorders. However, the five most costly disorders (€ million) were: dementia: €22,164; psychotic disorders: €16,717; mood disorders: €19,238; addiction: €11,719; anxiety disorders: €11,687. Apart from psychosis, these five disorders ranked amongst those with the lowest direct medical expenditure per subject (<€3000). The approximate breakdown of costs was: 50% indirect costs, 25% direct non-medical and 25% direct healthcare costs. Discussion: The prevalence and cost of UK brain disorders is likely to increase given the ageing population. Translational neurosciences research has the potential to develop more effective treatments but is underfunded. Addressing the clinical and economic challenges posed by brain disorders requires a coordinated effort at an EU and national level to transform the current scientific, healthcare and educational agenda.

Hand and foot surgery rates in rheumatoid arthritis have declined from 1986 to 2011, but large-joint replacement rates remain unchanged: results from two UK inception cohorts.

To assess whether there have been any secular changes in orthopedic interventions in patients with rheumatoid arthritis (RA) since 1986, as examined in 2 early rheumatoid arthritis (RA) inception cohorts with up to 25 years of followup.

Secular Changes in Clinical Features at Presentation of Rheumatoid Arthritis: Increase in Comorbidity But Improved Inflammatory States

To examine secular trends in demographics, clinical manifestations, and comorbidity on first presentation of rheumatoid arthritis (RA) prior to disease‐modifying antirheumatic drug treatment.

Association between rheumatoid arthritis disease activity, progression of functional limitation and long-term risk of orthopaedic surgery: combined analysis of two prospective cohorts supports EULAR treat to target DAS thresholds

Objectives To examine the association between disease activity in early rheumatoid arthritis (RA), functional limitation and long-term orthopaedic episodes. Methods Health Assessment Questionnaire (HAQ) disability scores were collected from two longitudinal early RA inception cohorts in routine care; Early Rheumatoid Arthritis Study and Early Rheumatoid Arthritis Network from 1986 to 2012. The incidence of major and intermediate orthopaedic surgical episodes over 25 years was collected from national data sets. Disease activity was categorised by mean disease activity score (DAS28) annually between years 1 and 5; remission (RDAS≤2.6), low (LDAS>2.6–3.2), low-moderate (LMDAS≥3.2–4.19), high-moderate (HMDAS 4.2–5.1) and high (HDAS>5.1). Results Data from 2045 patients were analysed. Patients in RDAS showed no HAQ progression over 5 years, whereas there was a significant relationship between rising DAS28 category and HAQ at 1 year, and the rate of HAQ progression between years 1 and 5. During 27 986 person-years follow-up, 392 intermediate and 591 major surgeries were observed. Compared with the RDAS category, there was a significantly increased cumulative incidence of intermediate surgery in HDAS (OR 2.59 CI 1.49 to 4.52) and HMDAS (OR 1.8 CI 1.05 to 3.11) categories, and for major surgery in HDAS (OR 2.48 CI 1.5 to 4.11), HMDAS (OR 2.16 CI 1.32 to 3.52) and LMDAS (OR 2.07 CI 1.28 to 3.33) categories. There was no significant difference in HAQ progression or orthopaedic episodes between RDAS and LDAS categories. Conclusions There is an association between disease activity and both poor function and long-term orthopaedic episodes. This illustrates the far from benign consequences of persistent moderate disease activity, and supports European League Against Rheumatism treat to target recommendations to secure low disease activity or remission in all patients.

Secular changes in clinical features at presentation of rheumatoid arthritis

To examine secular trends in demographics, clinical manifestations, and comorbidity on first presentation of rheumatoid arthritis (RA) prior to disease‐modifying antirheumatic drug treatment.

Rate of Decline of Kidney Function, Modality Choice, and Survival in Elderly Patients with Advanced Kidney Disease

Aim: In elderly, dependent patients with advanced chronic kidney disease, dialysis may confer only a small survival advantage over conservative kidney management (CKM). We investigated the role of rate of decline of kidney function on treatment choices and survival. Methods: We identified a retrospective (1995-2010) cohort of patients aged over 75 years, with progressive kidney impairment and an estimated glomerular filtration rate (eGFR) between 10 and 15 ml/min/1.73 m2. All subsequently chose to be treated by either dialysis or CKM. Patients were followed for a minimum of 3 years. Results: Of 250 patients identified, 92 (37%) opted for dialysis and 158 (63%) for CKM. Mean age was 80.9 ± 4.0 years. eGFR was 13.3 ± 1.4 initially and 8.7 ± 3.0 ml/min/1.73 m2 at follow-up. Both were similar in those on dialysis and CKM pathways. Rate of decline of eGFR was more rapid in those choosing dialysis (0.45 (interquartile range, IQR 0.64) vs. 0.21 (IQR 0.28) ml/min/1.73 m2/month, p < 0.001), and independently predicted choice of CKM. In patients with high comorbidity, choice of dialysis was associated with a non-significant adjusted survival advantage of 5 months. Inclusion in models of time dependent eGFR during follow-up (eGFRtd) - a reflection of the rate of decline of kidney function - showed it to be independently associated with mortality risk in those on the CKM (p < 0.001) but not on the dialysis pathway. CKM pathway patients at the 25th centile of eGFRtd had an adjusted survival of 7 months compared to 63 months for those at the 75th centile. Conclusions: Rate of decline of kidney function is a determinant of CKM choice in elderly patients and is associated with mortality risk in patients of the CKM pathway. These findings should inform counselling.

Reductions in Radiographic Progression in Early Rheumatoid Arthritis Over Twenty-Five Years: Changing Contribution From Rheumatoid Factor in Two Multicenter UK Inception Cohorts

To assess the 5‐year progression of erosions and joint space narrowing (JSN) and their associations with rheumatoid factor (RF) status in 2 large, multicenter, early rheumatoid arthritis cohorts, spanning 25 years.

Validation of methods for converting the original Disease Activity Score (DAS) to the DAS28

The Disease Activity Score (DAS) is integral in tailoring the clinical management of rheumatoid arthritis (RA) patients and is an important measure in clinical research. Different versions have been developed over the years to improve reliability and ease of use. Combining the original DAS and the newer DAS28 data in both contemporary and historical studies is important for both primary and secondary data analyses. As such, a methodologically robust means of converting the old DAS to the new DAS28 measure would be invaluable. Using data from The Early RA Study (ERAS), a sub-sample of patients with both DAS and DAS28 data were used to develop new regression imputation formulas using the total DAS score (univariate), and using the separate components of the DAS score (multivariate). DAS were transformed to DAS28 using an existing formula quoted in the literature, and the newly developed formulas. Bland and Altman plots were used to compare the transformed DAS with the recorded DAS28 to ascertain levels of agreement. The current transformation formula tended to overestimate the true DAS28 score, particularly at the higher end of the scale. A formula which uses all separate components of the DAS was found to estimate the scores with a higher level of precision. A new formula is proposed that can be used by other early RA cohorts to convert the original DAS to DAS28.

FRI0023 Five-year progression of rheumatoid arthritis disease activity and quality of life in 2002 and 2011. have reductions in disease activity in recent years resulted in improvements in quality of life?

Background The treat-to-target (T2T) approach, with earlier, aggressive treatment has resulted in improvements in rheumatoid arthritis (RA) outcomes1,2. Whether these improvements have translated into improvements in patient reported outcomes is less clear. Studies have indicated declines in pain and function as well as depression and anxiety. However, these studies are limited to short follow-up periods or were restricted to cross-sectional, rather than longitudinal analyses. Objectives To assess changes in 5 year progression rates for disease activity and patient reported outcomes in a prospective cohort of early RA patients between 2002 and 2011. Methods The Early RA Network (ERAN) is a longitudinal prospective cohort study that recruited 1236 early RA patients from 2002 to 2011. DAS-28 and SF-36 were measured at baseline, 6 months, 12 months and then yearly. Multi-level linear regression were used to model 5 year progression rates of both DAS-28 and SF-36 in patients recruited between 2002–2011. Models controlled for sex and age and seropostivity at baseline. DMARD use at baseline was controlled for using propensity score weighting. Year of diagnosis was entered as a continuous variable, allowing for the mean of the outcome variables to be estimated for 2002 and 2011. Restricted cubic splines were used to account for non-linear progression over time. Results Disease activity for patients diagnosed in 2011 demonstrated a statistically significant decrease at year 5 compared to patients diagnosed in 2002 (5 year estimated mean difference −0.35; 95% CI 0.22–0.49, p<0.001). Using the SF-36 measure, Physical Function, Bodily Pain, Vitality (indicating fatigue) and Mental Health indicated similar levels at year-5 between those patients diagnosed in 2011 to those diagnosed in 2002 (p>0.05). Mental health was similar to the normalised population mean of 50, irrespective of year diagnosed. However, levels of vitality/fatigue, function and pain remain less favourable for all early RA patients over the first 5 years. Conclusions Although disease activity has shown a marked decline at 5 years between 2002 and 2011, there is little evidence that this has led to improvements of an equivalent magnitude in function, pain, fatigue and mental health. Treatment should also focus on improved function, pain management, fatigue and mental health as part of the T2T protocol. References [1] Twigg S, et al. Fatigue, older age, higher body mass index and female gender predict worse disability in early rheumatoid arthritis despite treatment to target: A comparison of two observational cohort studies from the United Kingdom. Arthritis Care Res. (Hoboken). 2017. doi:10.1002/acr.23281 [2] Carpenter L, et al. Reductions in Radiographic Progression in Early Rheumatoid Arthritis Over Twenty-Five Years: Changing Contribution from Rheumatoid Factor in Two Multicenter UK Inception Cohorts. Arthritis Care Res. 2017;69. Disclosure of Interest None declared

Non-adherence to immunosuppressants following renal transplantation: a protocol for a systematic review

Introduction Adherence to immunosuppressant medication is essential for renal transplant recipients. This review aims to summarise what is known about non-adherence, with a view to providing comprehensive evidence to inform strategies aimed at advancing adherent behaviour. Methods and analysis A systematic review of quantitative studies that report adherence to immunosuppressants in adult (over 18 years) renal transplant recipients. The review will follow the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines; study quality will be assessed using the Downs and Black checklist. Systematic searches will be completed across relevant databases. Two reviewers will independently extract data using a predefined data extraction form. We will summarise the operationalisation of adherence across studies and use narrative synthesis to identify factors associated with non-adherence. A meta-analysis will be conducted if there is sufficient homogeneity, and available data, across studies to estimate the prevalence of non-adherence in renal transplant recipients. Heterogeneity will be assessed using the I2 test. Survival analysis will be conducted to estimate hazard ratios to explore the impact of non-adherence on graft survival, graft failure and patient survival. Ethics and dissemination Findings will be published in a peer-reviewed journal and disseminated at conferences for professionals and researchers. Review outcomes will help support clinical practice by highlighting the extent of non-adherence among adults, and in doing so, signpost the need for suitable intervention. Trial registration number PROSPERO registration number (CRD42016038751).