SummaryBackgroundExposure to ambient air pollution increases morbidity and mortality, and is a leading contributor to global disease burden. We explored spatial and temporal trends in mortality and burden of disease attributable to ambient air pollution from 1990 to 2015 at global, regional, and country levels.MethodsWe estimated global population-weighted mean concentrations of particle mass with aerodynamic diameter less than 2·5 μm (PM2·5) and ozone at an approximate 11 km × 11 km resolution with satellite-based estimates, chemical transport models, and ground-level measurements. Using integrated exposure–response functions for each cause of death, we estimated the relative risk of mortality from ischaemic heart disease, cerebrovascular disease, chronic obstructive pulmonary disease, lung cancer, and lower respiratory infections from epidemiological studies using non-linear exposure–response functions spanning the global range of exposure.FindingsAmbient PM2·5 was the fifth-ranking mortality risk factor in 2015. Exposure to PM2·5 caused 4·2 million (95% uncertainty interval [UI] 3·7 million to 4·8 million) deaths and 103·1 million (90·8 million 115·1 million) disability-adjusted life-years (DALYs) in 2015, representing 7·6% of total global deaths and 4·2% of global DALYs, 59% of these in east and south Asia. Deaths attributable to ambient PM2·5 increased from 3·5 million (95% UI 3·0 million to 4·0 million) in 1990 to 4·2 million (3·7 million to 4·8 million) in 2015. Exposure to ozone caused an additional 254 000 (95% UI 97 000–422 000) deaths and a loss of 4·1 million (1·6 million to 6·8 million) DALYs from chronic obstructive pulmonary disease in 2015.InterpretationAmbient air pollution contributed substantially to the global burden of disease in 2015, which increased over the past 25 years, due to population ageing, changes in non-communicable disease rates, and increasing air pollution in low-income and middle-income countries. Modest reductions in burden will occur in the most polluted countries unless PM2·5 values are decreased substantially, but there is potential for substantial health benefits from exposure reduction.FundingBill & Melinda Gates Foundation and Health Effects Institute.

ObjectivesTo compare the prevalence, clinical and radiographic characteristics of psoriatic spondyloarthritis (PsSpA) in psoriatic arthritis (PsA), with ankylosing spondylitis (AS).MethodsA prospective single-centre cross-sectional observational study recruited consecutive PsA and AS cases. Participants completed outcome measures, and underwent clinical examination, axial radiographic scoring and HLA-sequencing. Multivariable analyses are presented.ResultsThe 402 enrolled cases (201 PsA, 201 AS; fulfilling classification criteria for respective conditions) were reclassified based upon radiographic axial disease and psoriasis, as: 118 PsSpA, 127 peripheral-only PsA (pPsA), and 157 AS without psoriasis (AS) cases. A significant proportion of patients with radiographic axial disease had PsSpA (118/275; 42.91%), and often had symptomatically silent axial disease (30/118; 25.42%). Modified New York criteria for AS were fulfilled by 48/201 (23.88%) PsA cases, and Classification of Psoriatic Arthritis criteria by 49/201 (24.38%) AS cases. pPsA compared with PsSpA cases had a lower frequency of HLA-B*27 (OR 0.12; 95% CI 0.05 to 0.25). Disease activity, metrology and disability were comparable in PsSpA and AS. A significant proportion of PsSpA cases had spondylitis without sacroiliitis (39/118; 33.05%); they less frequently carried HLA-B*27 (OR 0.11; 95% CI 0.04 to 0.33). Sacroiliac joint complete ankylosis (adjusted OR, ORadj 2.96; 95% CI 1.42 to 6.15) and bridging syndesmophytes (ORadj 2.78; 95% CI 1.49 to 5.18) were more likely in AS than PsSpA. Radiographic axial disease was more severe in AS than PsSpA (Psoriatic Arthritis Spondylitis Radiology Index Score: adjusted incidence risk ratio 1.13; 95% CI 1.09 to 1.19).ConclusionsIn a combined cohort of patients with either PsA or AS from a single centre, 24% fulfilled classification criteria for both conditions. The pattern of axial disease was influenced significantly by the presence of skin psoriasis and HLA-B*27.

We report significant and clinically meaningful improvements in both work disability and clinical outcomes after commencement of anti-TNF therapy in a real-world setting. Improvements in all outcomes among those commencing csDMARDs were slower and of a smaller magnitude.

Objective. Juvenile-and adult-onset ankylosing spondylitis (AS) are subtypes of AS that may have different clinical outcomes. We compared cohorts of juvenile-onset AS and adult-onset AS in terms of clinical characteristics, clinical outcomes, proceeding to AS-related orthopedic surgery, and type of orthopedic surgery. Methods. A retrospective cohort study was conducted of all AS patients attending a teaching hospital. Demographics, clinical parameters, and history of AS-related orthopedic surgery to the spine, root, or peripheral joints were recorded. Differences between surgery for juvenile-and adult-onset AS patients, and effects of covariates were assessed using logistic regression and survival analyses. Results. A total of 553 AS patients were studied: 162 juvenile-onset AS and 391 adult-onset AS cases. After adjusting for significant covariates, adult-onset AS cases were less likely to proceed to surgery (odds ratio [OR] 0.31, P < 0.001), have a hip procedure (resurfacing or arthroplasty; OR 0.374, P 5 0.001), and have hip arthroplasty (OR 0.43, P 5 0.01). Significant differences were also observed when comparing Kaplan-Meier survival curves (P 5 0.001) and using Cox proportional hazards regression (P 5 0.002). A history of smoking was not associated with surgery. AS cases with older age at symptom onset were far less likely to have surgery than those with younger onset, in a nonlinear manner. Conclusion. Juvenile-onset AS cases are more likely than adult-onset AS cases to proceed to hip arthroplasty, but equally likely to have hip resurfacing and hip arthroplasty revision/re-revisions. Smoking was not associated with the risk of orthopedic surgery. Orthopedic surgery was unlikely after 40 years of disease in both subsets.

Background Diagnostic delay (DD) in Ankylosing Spondylitis (AS) remains a challenge, averaging 8.6 years1. Chronic back pain comprises 2.6million GP consultations per year, of which 5% have AS2. Identifying this “needle in a haystack” is compounded by poor appreciation of inflammatory back pain and lack of appropriate use of MRI early in diagnosis. The advent of biologic therapy with potential to induce remission makes early diagnosis increasingly important. There is paucity of data on the impact of DD on disease burden in AS. Published data suggests DD correlates to high disease activity, functional impairment, poor metrology and work disability (WD)3,4. DD and WD correlate to reduced survival in AS5. Objectives Primarily to assess the impact of DD on Bath AS Metrology Index (BASMI) and current work status (cWS) Secondarily to assess the impact of DD on Bath AS disease activity Index (BASDAI), Bath AS Functional Index (BASFI) and current Tumour Necrosis Factor inhibitor use (cTNFU) Methods This was a retrospective cohort study of AS patients meeting modified New York criteria. Time from symptom onset to diagnosis (DD) was correlated to BASMI, BASDAI and BASFI within a year of diagnosis, cWS in those under 60 years and cTNFU. The confounding effects of age, HLA B27 status, family history of AS and smoking were accounted for by statistical modelling Results Data on 106 patients was analysed. 79% were male. Mean age at symptoms onset was 24.5years (±SD 9.8) and at diagnosis was 35.5 (±14.0). Mean DD was 10.5 (±11.9). Gender made no significant difference to DD (p=0.4) BASMI score increased by 0.06 for each year of DD (p=0.0002) and age at diagnosis (p=0.015) when measured independently. However when DD was corrected for age the BASMI rise was not significant, indicating that age remained a significant predictor (p=0.039) 33% of patients were Work disabled (WD). Gender had no significant impact on cWS (p=0.1). The Work enabled (WE) had significantly shorter DD than the WD (median 7.8 vs.16.6 years, p=0.005). The risk of being WD increased by 6.6% for each year of DD (OR=1.067, CI=1.03–1.1; p=0.0009) Age at diagnosis was a significant predictor of cWS (p=0.008). The risk of being WD increased to peak at 38.5 years and declined thereafter. HLA B27 positive patients had 6 fold higher odds of being WE (OR=6.2, CI=1.6–24.8) DD did not have a significant effect on BASDAI (p=0.8), BASFI (p=0.6) or cTFNU (p=0.9) Conclusions DD caused significantly worse mobility and WD. Both outcomes were highly dependent on age at diagnosis. The peak risk of WD was in the age group that contributes the most to family and national economy. Unlike the published data, we did not find a significant impact of DD on BASDAI, BASFI or cTNFU. Our findings underpin the importance of minimising DD in AS. References Hamilton L et al. Services for people with Ankylosing Spondylitis in the UK-a survey of Rheumatologists and patients. Rheum 2011;50:1991-8 Underwood MR et al. Inflammatory Back pain in primary care. Br J Rheum 1995;34(11):1074...

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BackgroundDisease activity in rheumatoid arthritis (RA) has traditionally been measured using the 28-joint count disease activity score (DAS28) using ESR. Use of DAS28 with CRP in place of ESR is increasing. Evidence suggests these scores are not truly interchangeable and agreement varies dependant on disease activity. This study uses the BSRBR-RA to investigate agreement between these scores, proposing an optimised method to calculate the estimated DAS28-ESR using CRP (mDAS28-CRP) that offers higher interscore agreement than currently.ObjectivesTo investigate and optimise agreement between the DAS28-ESR and DAS28-CRP scores using the BSRBR-RA.MethodsPatients with concurrent measures of ESR and CRP were identified from the BSRBR-RA, enabling paired calculation of DAS28-ESR and DAS28-CRP using existing formulae. A non-linear regression model enabled prediction of ESR from CRP. Resulting values were used in the existing DAS28-ESR formula to calculate estimated disease activity (mDAS28-CRP). A Bayesian approach was used to acknowledge the uncertainty associated with the predictions and correctly propagate it through to mDAS28-CRP. Inference, including constructing credible intervals for predicted ESR and mDAS28-CRP, was performed using Markov-Chain-Monte-Carlo. Bland-Altman analysis and agreement matrices were used to compare agreement levels between mDAS28-CRP, DAS28-CRP and DAS28-ESR.Results5457 patients (mean age 56 yrs, 76% female) with 31,084 data entries were identified where paired DAS28-ESR/DAS28-CRP scores could be calculated. Mean DAS28-ESR was 0.3 points greater than DAS28-CRP (4.4 (SD 1.7), 4.1 (SD 1.6) respectively) compared with mean mDAS28-CRP of 4.6 (SD 1.6; Fig 1). mDAS28-CRP had superior agreement with DAS28-ESR across remission, low and moderate disease activity, with only a 6.8% reduction in agreement at high disease activity when compared with the DAS28-CRP (Table 1).Table 1.Comparison of agreement between DAS28-ESR, DAS28-CRP and mDAS28-CRP scoresDAS28-ESRRemission (<2.6)LDA (2.6 to ≤3.2)MDA (3.2 to ≤5.2)HDA >5.2Totals15.6% (n=4857)11.1% (n=3440)38.0% (n=11810)35.3% (n=10977)100% (31084)Remission (<2.6)DAS28-CRP66.7% (4041)25.4% (1541)7.9% (481)019.5% (6063)mDAS28-CRP84.6% (2720)13.9% (446)1.6% (51)010.3% (3217)LDA (2.6 to ≤3.2)DAS28-CRP15.8% (646)32.0% (1303)52.2% (2128)013.1% (4077)mDAS28-CRP42.1% (1487)39.2% (1384)18.7% (662)011.4% (3533)MDA (3.2 to ≤5.2)DAS28-CRP1.4% (170)4.9% (591)73.7% (8881)20.0% (2414)38.8% (12056)mDAS28-CRP5.0% (650)12.3% (1601)76.5% (9916)6.4% (837)41.8% (13004)HDA >5.2DAS28-CRP00.1% (5)3.6% (320)96.3% (8563)28.6% (8888)mDAS28-CRP00.1% (9)10.4% (1181)89.5% (10140)36.4% (11330)LDA, low disease activity; MDA, moderate disease activity; HDA, high disease activity.ConclusionsThe mDAS28-CRP (online calculator pending) allows calculation of a disease activity score, using the same component parts of the DAS28-CRP, and has higher agreement levels with the original validated DAS28-ESR, than the current DAS28-CRP in this cohort. Disease activity scores are fundamental in clinic...

BackgroundWork disability (WD) in Psoriatic Arthritis (PsA) is high with unemployment reported at 20-50% and presenteeism (reduced effectiveness at work) at 16-39%. We have previously reported that presenteeism is primarily associated with measures of disease activity whereas unemployment, considered the endpoint of work disability, is associated with employer factors, age and disease duration. Randomised trials have established the effectiveness of biologic agents on presenteeism in PsA. The effect of DMARD or anti-TNF treatment in a real world population has not been studied.ObjectivesTo investigate work disability (presenteeism and productivity loss) after commencement of standard clinical treatment (anti-TNF and DMARD) in a real life cohort of patients with PsA.MethodsFour hundred patients fulfilling CASPAR criteria for PsA were recruited from 23 hospitals across the UK. Demographic, socioeconomic, work and clinical data were collected at baseline prior to commencement of anti-TNF or DMARD. Follow up was scheduled for 2, 4, 12 and 24 weeks as part of routine practice. WD was assessed with the Work Productivity and Activity Questionnaire (WPAI-SHP) and disease activity with the DAPSA composite measure. Analysis was on intention to treat. Differences within and between groups were assessed using the Mann-Whitney U test and by calculating nonparametric 95% confidence intervals for differences using bootstrapping.ResultsTwo hundred and thirty six participants of any age were in work. Unemployed patients were older, 59yrs (IQR 47.7-67.8) vs 49yrs (IQR 41.7-58.0) and had worse physical function (HAQ) 1.4 (IQR 0.75-1.94) vs 1.0 (IQR 0.50-0.86) but other demographic and clinical measures were not significantly different. Patients commenced on anti-TNF had longer disease duration 11yrs (IQR 3.5-18.5) vs 5yrs (IQR 2-11) and higher tender, 16 (IQR 11-25) vs 11 (IQR 5-20.25) and swollen 7 (IQR 5-12) vs 5 (IQR 2-10) joint counts but other demographic and clinical measures were not significantly different. Amongst those commencing anti-TNF presenteeism improved from 40% (IQR 20-60) to 10% (IQR 0-30) (p0.001) and productivity loss from 45% (IQR 26.2-67-8) to 10% (IQR 0-30.0) (p0.001). Amongst those commencing DMARD presenteeism improved from 30% (IQR10-60) to 20% (IQR10-50) p=0.001 and productivity loss from 40% (IQR 20-70) to 25 (IQR 10-60) (p0.001). The difference in change of presenteeism between groups became significant at 2 weeks and was sustained to 24 weeks (figure 1). There were no significant changes in employment level in either treatment group. DAPSA improved over 24 weeks from 53 (IQR 38.3-68.4) to 14 (6.9-37.4) in the anti-TNF group (p0.001), defined as a good response using established cut points vs 39 (IQR 27.9-58.4) to 30 (IQR 18.4-38.5) in the DMARD group (p0.001) defined as a poor response.Figure 1.Change in presenteeism over 24 weeks post initiation of anti-TNF/DMARD. Key: Box plot: Median and IQR, Bullet: Mean and 95% CI for differences.ConclusionsWe observed a clinically significant improvement in prese...