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Objective: To investigate how social support, financial status, and lifestyle influence the development of excess disability in rheumatoid arthritis (RA). Methods: Data were obtained from the Étude et Suivi des Polyarthrites Indifférenciées Récentes (ESPOIR) cohort study of people with RA. A previous analysis identified groups with similar inflammation trajectories but markedly different disability over 10 years; those in the higher disability trajectory groups were defined as having “excess disability.” Self-reported data regarding contextual factors (social support, financial situation, lifestyle) were obtained from participants, and they completed patient-reported outcome measures (pain, fatigue, anxiety, depression) at baseline. The direct effect of the contextual factors on excess disability and the effect mediated by patient-reported outcome measures were assessed using structural equation models. Findings were validated in 2 independent data sets (Norfolk Arthritis Register [NOAR], Early Rheumatoid Arthritis Network [ERAN]). Results: Of 538 included ESPOIR participants (mean age ± SD 48.3 ± 12.2 years; 79.2% women), 200 participants (37.2%) were in the excess disability group. Less social support (β = 0.17 [95% confidence interval (95% CI) 0.08, 0.26]), worse financial situation (β = 0.24 [95% CI 0.14, 0.34]), less exercise (β = 0.17 [95% CI 0.09–0.25]), and less education (β = 0.15 [95% CI 0.06, 0.23]) were associated with excess disability group membership; smoking, alcohol consumption, and body mass index were not. Fatigue and depression mediated a small proportion of these effects. Similar results were seen in NOAR and ERAN. Conclusion: Greater emphasis is needed on the economic and social contexts of individuals with RA at presentation; these factors might influence disability over the following decade.

Objectives To identify groups of people with RA with different disability trajectories over 10 years, despite comparable levels of inflammation. Methods Data for this analysis came from three European prospective cohort studies of people with RA [Norfolk Arthritis Register (NOAR), Early RA Network (ERAN), Étude et Suivi des Polyarthrites Indifférenciées Récentes (ESPOIR)]. Participants were assessed regularly over 8 (ERAN) to 10 (NOAR/ESPOIR) years. Inclusion criteria were: recruited after 1 January 2000, Results This analysis included 2500 people with RA (NOAR: 1000, ESPOIR: 766, ERAN: 734). ESPOIR included more women and the participants were younger [mean (standard deviation) age: NOAR: 57.1 (14.6), ESPOIR: 47.6 (12.5), ERAN: 56.8 (13.8); women: NOAR: 63.9%, ESPOIR: 76.9%, ERAN: 69.1%). Within each cohort, two pairs of trajectories following the hypothesized pattern (comparable DAS28-2Cs but different HAQs) were identified. Higher pain, fatigue and depressive symptoms were associated with increased odds of being in the high HAQ trajectories. Conclusion Excess disability is persistent in RA. Controlling inflammation may not be sufficient to alleviate disability in all people with RA, and effective pain, fatigue and mood management may be needed in some groups to improve long-term function.

Background Clinical prediction models (CPMs) predict the risk of health outcomes for individual patients. The majority of existing CPMs only harness cross-sectional patient information. Incorporating repeated measurements, such as those stored in electronic health records, into CPMs may provide an opportunity to enhance their performance. However, the number and complexity of methodological approaches available could make it difficult for researchers to explore this opportunity. Our objective was to review the literature and summarise existing approaches for harnessing repeated measurements of predictor variables in CPMs, primarily to make this field more accessible for applied researchers. Methods MEDLINE, Embase and Web of Science were searched for articles reporting the development of a multivariable CPM for individual-level prediction of future binary or time-to-event outcomes and modelling repeated measurements of at least one predictor. Information was extracted on the following: the methodology used, its specific aim, reported advantages and limitations, and software available to apply the method. Results The search revealed 217 relevant articles. Seven methodological frameworks were identified: time-dependent covariate modelling, generalised estimating equations, landmark analysis, two-stage modelling, joint-modelling, trajectory classification and machine learning. Each of these frameworks satisfies at least one of three aims: to better represent the predictor-outcome relationship over time, to infer a covariate value at a pre-specified time and to account for the effect of covariate change. Conclusions The applicability of identified methods depends on the motivation for including longitudinal information and the method’s compatibility with the clinical context and available patient data, for both model development and risk estimation in practice.

ObjectivesWork is an important health outcome. This study aimed to identify predictors of work loss, absenteeism and presenteeism over 1 year in RA patients commencing treatment with MTX or biologics.MethodsPatients aged 18–65 years in full/part-time employment from two UK prospective cohorts were included: MTX-starters = Rheumatoid Arthritis Medication Study; and biologic-starters = Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate. Presenteeism and absenteeism were assessed using the RA-specific Work Productivity Survey at baseline, and 6 and 12 months. Potential predictors including baseline age, gender, clinical measures (e.g. disability, pain, fatigue), psychological distress, occupation and EULAR response from baseline to 6 months were investigated.ResultsA total of 51/463 MTX-starters and 30/260 biologic-starters left work over 12 months. Higher baseline psychological distress in MTX-starters [odds ratio (OR) 1.1 (95% CI: 1.0, 1.1)] and higher disability in biologic-starters [OR 3.5 (95% CI: 1.4, 8.6)] predicted work loss. Some 16.1% of patients reported sick-leave, which was predicted by disability [OR (95% CI): MTX-starters: 1.5 (0.9, 2.3); biologic-starters: 2.4 (1.1, 5.2)]. Median presenteeism scores were very low (minimal interference) in both cohorts. Higher fatigue for MTX starters [incidence rate ratio 1.2 (95% CI: 1.0, 1.4)] and higher disability in biologic-starters (incidence rate ratio 1.4 (95% CI: 1.1, 1.7)] predicted presenteeism. Good EULAR response was associated with lower absenteeism and presenteeism in both cohorts.ConclusionPatients with RA still face significant limitations regarding their ability to work. Disability and EULAR response were the main predictors of work outcomes, emphasizing the need to control the disease and the importance of function in enabling work participation.

Summary: Background: Factors that might influence response to systemic treatment for moderate‐to‐severe psoriasis are varied, and generally, are poorly understood, aside from high bodyweight, suggesting that other unidentified factors may be relevant in determining response to treatment. The impact of alcohol misuse on treatment response has not been previously investigated. Objectives: To investigate whether alcohol misuse is associated with poor response to treatment for psoriasis. Methods: This was a prospective cohort study in which response to systemic therapies was assessed using the Psoriasis Area and Severity Index (PASI). The CAGE (Cut down, Annoyed, Guilty, Eye opener) questionnaire was used to screen for alcohol misuse. A multivariable factional polynomial linear regression model was used to examine factors associated with change in PASI between baseline and follow‐up. Results: The cohort comprised 266 patients (biologic cohort, n = 134; conventional systemic cohort, n = 132). For the entire cohort, the median (interquartile range) PASI improved from 13 (10·0–18·3) at baseline to 3 (1·0–7·5) during follow‐up. A higher CAGE score [regression coefficient: 1·40, 95% confidence interval (CI) 0·04–2·77]; obesity (1·84, 95% CI 0·48–3·20); and receiving a conventional systemic rather than a biologic therapy (4·39, 95% CI 2·84–5·95) were significantly associated with poor response to treatment; whereas a higher baseline PASI (–0·83, 95% CI –0·92 to –0·74) was associated with a better response to treatment. Conclusions: The poor response to therapy associated with alcohol misuse and obesity found in people with psoriasis calls for lifestyle behaviour change interventions and support as part of routine clinical care. Targeting interventions to prevent, detect and manage alcohol misuse among people with psoriasis is needed to minimize adverse health consequences and improve treatment response.

OBJECTIVE: To determine the association between osteoarthritis (OA), rheumatoid arthritis (RA), and frailty and to determine whether comorbidities interact with OA and RA to further increase the likelihood of frailty.METHODS: Participants of the UK Biobank age 40-69 years at baseline were included. Demographic, lifestyle, and clinical data were collected at baseline and follow-up in a subset. Frailty was assessed using a frailty index (FI) (continuous) and a modified frailty phenotype (robust, pre-frail, frail). The association between RA and OA and frailty at baseline and follow-up was assessed using multiple regression models. We looked at whether comorbidities, including cardiovascular disease, diabetes mellitus, chronic obstructive pulmonary disease, and depression interacted additively with OA and RA to increase the likelihood of frailty.RESULTS: In total, 457,561 participants contributed data. Those with (versus without) RA (n = 4,894) and OA (n = 35,884), respectively, were more likely to be frail (adjusted relative risk ratio 10.7 [95% confidence interval (95% CI) 9.7, 11.7] and 3.4 [95% CI 3.3, 3.6]) and were more likely to have a higher FI at baseline. There was evidence of additive interaction between RA, OA, and common comorbidities increasing the occurrence of prevalent frailty. Among 25,163 participants included in longitudinal analysis, patients with RA (n = 202) and OA (n = 1,811) at baseline had an increased adjusted frailty incidence rate ratio (2.8 [95% CI 1.7, 4.6] and 1.7 [95% CI 1.3, 2.1], respectively) and also a higher FI during follow-up.CONCLUSION: Individuals with RA and OA are more likely to have, or develop, frailty. Common comorbidities interact with OA and RA to further increase the likelihood of frailty.

Objectives To characterize the incidence of clinically diagnosed Paget’s disease of bone in the UK during 1999–2015 and to determine variations in the incidence of disease by age, sex, geography and level of deprivation. Methods Incident cases of Paget’s disease occurring between 1999 and 2015 were identified from primary care records. Overall crude incidence and incidence stratified by age and sex was calculated each year from 1999 to 2015. Direct age- and sex-standardized incidence was also calculated. We used Poisson regression to look at variations in incidence by deprivation and UK region. Results A total of 3592 incident cases of Paget’s disease were identified between 1999 and 2015. Incidence increased with age and at all ages was greater in men than women. In women and men, respectively, crude incidence increased from 0.037 and 0.074/10 000 population per year among those 45–49 years of age to 3.7 and 6.3/10 000 population per year among those ≥85 years. The overall standardized incidence decreased from 0.75/10 000 person-years in 1999 to 0.20/10 000 person-years in 2015. After adjustment for age and sex, incidence was >30% higher in the most- compared with least-deprived quintile of deprivation. There was evidence of geographic variation, with the highest incidence in the North West of England, which persisted after adjustment for age, sex and level of deprivation. Conclusion The incidence of clinically diagnosed Paget’s disease has continued to decrease since 1999. The reason for the decline in incidence remains unknown, although the rapidity of change points to an alteration in one or more environmental determinants.

Importance Treatments for psoriasis may be less effective in everyday practice than in clinical trials. Emulating a target trial using data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) can provide treatment effect estimates that are robust and can inform both clinicians and regulatory bodies. Objectives To assess the comparative effectiveness of ustekinumab and secukinumab in patients with psoriasis, and to test whether the relative effectiveness estimate of the CLEAR trial, a randomized clinical trial that compared secukinumab with ustekinumab for psoriasis, can be replicated. Design, Setting, and Participants This comparative effectiveness research study used a target trial emulation approach and was performed between November 2007 and August 2019. Data were obtained from BADBIR, a multicenter longitudinal pharmacovigilance register of patients with moderate to severe psoriasis in the United Kingdom and Republic of Ireland. Participants had chronic plaque psoriasis, were 18 years or older, and had at least 1 record of a Psoriasis Area and Severity Index (PASI) of 12 or higher before their initiation to secukinumab or ustekinumab. Propensity score (PS) 1:1 matched analysis and inverse probability treatment weighted analysis were performed. Main Outcomes and Measures The primary outcomes were the risk ratio (RR) and the risk difference (RD) for achieving PASI of 2 or lower after 12 months of therapy for secukinumab compared with ustekinumab. Methods to account for missing outcome data were complete case analysis, nonresponder imputation, last observation carried forward, inverse probability of censoring weighting, and multiple imputation. Regulatory and estimate agreement metrics were used to benchmark the effect estimates in this study against those in the CLEAR trial. Results A total of 1231 patients were included in the analysis, with 917 receiving ustekinumab and 314 receiving secukinumab. Secukinumab was superior to ustekinumab in all analyses, except under the nonresponder imputation method, in the proportion of participants achieving a PASI of 2 or lower (PS-weighted complete case analysis: RR, 1.28 [95% CI, 1.06-1.55]; RD, 11.9% [1.6-22.1]). All analyses, except for nonresponder imputation, reached regulatory agreement in both PS-matching and PS-weighted analyses. Conclusions and Relevance This comparative effectiveness study found that secukinumab resulted in more patients achieving a PASI of 2 or lower after 12 months of therapy compared with ustekinumab in patients with psoriasis. Target trial emulation in this study resulted in regulatory and estimate agreement with the CLEAR randomized clinical trial; further such studies may help fill the evidence gap when comparing other systemic therapies for psoriasis.

With sustained growth of diabetes numbers, sustained patient engagement is essential. Using nationally available data, we have shown that the higher mortality associated with a diagnosis of T1DM/T2DM could produces loss of 6.4 million future life years in the current UK population. In the model, the 'average' person with T1DM (age 42.8 years) has a life expectancy from now of 32.6 years, compared to 40.2 years in the equivalent age non diabetes mellitus population, corresponding to lost life years (LLYs) of 7.6 years/average person. The 'average' person with T2DM (age 65.4 years) has a life expectancy from now of 18.6 years compared to the 20.3 years for the equivalent non diabetes mellitus population, corresponding to LLY of 1.7 years/average person. We estimate that for both T1DM and T2DM, one year with HbA1c >58 mmol/mol loses around 100 life days. Linking glycaemic control to mortality has the potential to focus minds on effective engagement with therapy and lifestyle recommendation adherence.

Background The US opioid epidemic has led to similar concerns about prescribed opioids in the UK. In new users, initiation of or escalation to more potent and high dose opioids may contribute to long-term use. Additionally, physician prescribing behaviour has been described as a key driver of rising opioid prescriptions and long-term opioid use. No studies to our knowledge have investigated the extent to which regions, practices, and prescribers vary in opioid prescribing whilst accounting for case mix. This study sought to (i) describe prescribing trends between 2006 and 2017, (ii) evaluate the transition of opioid dose and potency in the first 2 years from initial prescription, (iii) quantify and identify risk factors for long-term opioid use, and (iv) quantify the variation of long-term use attributed to region, practice, and prescriber, accounting for case mix and chance variation. Methods and findings A retrospective cohort study using UK primary care electronic health records from the Clinical Practice Research Datalink was performed. Adult patients without cancer with a new prescription of an opioid were included; 1,968,742 new users of opioids were identified. Mean age was 51 ± 19 years, and 57% were female. Codeine was the most commonly prescribed opioid, with use increasing 5-fold from 2006 to 2017, reaching 2,456 prescriptions/10,000 people/year. Morphine, buprenorphine, and oxycodone prescribing rates continued to rise steadily throughout the study period. Of those who started on high dose (120–199 morphine milligram equivalents [MME]/day) or very high dose opioids (≥200 MME/day), 10.3% and 18.7% remained in the same MME/day category or higher at 2 years, respectively. Following opioid initiation, 14.6% became long-term opioid users in the first year. In the fully adjusted model, the following were associated with the highest adjusted odds ratios (aORs) for long-term use: older age (≥75 years, aOR 4.59, 95% CI 4.48–4.70, p < 0.001; 65–74 years, aOR 3.77, 95% CI 3.68–3.85, p < 0.001, compared to, In this analysis of electronic health records, Meghna Jani and colleagues investigate how opioids are prescribed in UK primary care patients., Author summary Why was this study done? Whilst opioid prescribing for non-cancer pain has risen in the US and Canada, trends over time are less clear in the UK. No studies to our knowledge have evaluated how opioid dose/potency changes over time in UK patients started an opioid for the first time for non-cancer pain, to assess escalation, tapering, and long-term use. Physician prescribing behaviour has been implicated as a key driver of rising opioid prescriptions and long-term opioid use; however, this needs to be interpreted in the context of regional and individual patient differences. The association of region, practice, prescriber, and individual factors with long-term opioid use is highly important, as this has implications for policy and future targeted public health interventions. What did the researchers do and find? We conducted a study of 1,968,742 new opioid users without cancer from primary care electronic health records across the UK. We found that between 2006 and 2017 codeine was the most commonly prescribed opioid: There was a 5-fold increase in codeine prescriptions, a 7-fold increase in tramadol prescriptions, and a 30-fold increase in oxycodone prescriptions for non-cancer pain. Prescribing factors (e.g., high dose/potency of opioid or concurrent gabapentinoid use), older age, higher socioeconomic deprivation score, and other conditions including fibromyalgia, rheumatological conditions, history of substance abuse, suicide/self-harm, alcohol abuse, and major surgery were associated with long-term opioid use. After accounting for individual patient factors, the North West, Yorkshire and the Humber, and South West regions of England were associated with a higher risk of long-term opioid use. Whilst there were only 3.5% of prescribers who had significantly higher prescribing practices leading to long-term use after adjustment of patient factors, where they did, rates were up to 3.5 times higher than the population average. What do these findings mean? Clinicians should take care in prescribing high dose opioids at initiation and closely monitor those with the above individual factors for long-term use. The variation observed across regions, practices, and prescribers after adjustment for patient factors supports calls for action to reduce such variation and harmonise prescribing practices.

IntroductionEcological studies show association between antimicrobial resistance (AMR), and inappropriate oral antibiotics use. Moderating antibiotic prescribing requires an understanding of all drivers of local prescribing. The aim was to quantify how much is determined by external factors compared with discretionary clinical choices.MethodsOral antibiotic usage taken from England General Practitioner/Family Doctor practice prescribing data was aggregated using WHO/ATC defined daily doses (DDDs). The average annual antibiotic daily prescribing rate (AAADPR) in each practice was the total DDD of oral antibiotics divided by registered population and 365. The AAADPR of English practices in 2017_18 was linked by regression to factors including demographics, geography, medical comorbidities, clinical performance, patient satisfaction, medical workforce characteristics and prescribing selection. The regression coefficients for modifiable prescribing selection factors were applied to the difference between the median and top decile practice values to establish overall reduction opportunities through changing prescribing behaviour.ResultsTwenty five factors accounted for 58% of the AAADPR variation in 5889 practices supporting 49.8 million patients. Non‐modifiable factors linked increased AAADPR to more northerly location, higher prevalence of diabetes, COPD, CHD, and asthma; higher white ethnicity; higher patient satisfaction and lower population density. Modifiable behaviour accounted for 11% of the variation in AAADPR, with increases associated with a wider range of antibiotics, higher proportion taken as liquids, higher doses in each prescription, lower guideline compliance, lower targeted antibiotics, lower spend/dose, and less seasonal variation. If all practices achieved the level of modifiable factors of the top decile, this model suggests that overall AAADPR could reduce by 31%.ConclusionSuch analysis is associative and does not infer causation. However, demographics, location, medical condition of the population, and prescribing selection are drivers of overall antibiotic prescribing. This analysis provides benchmarks for both non‐modifiable and modifiable factors against which practices could evaluate their opportunities to reduce antibiotic prescribing.

Introduction: Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the name given to the 2019 novel coronavirus. COVID-19 is the name given to the disease associated with the virus. SARS-CoV-2 is a new strain of coronavirus not been previously identified in humans. Methods: Two key factors, case incidence and case morbidity, were analysed for England. When taken together they give an estimate of relative demand on healthcare utilisation. To analyse case incidence, the latest values for indicators that could be associated with infection transmission rates were collected from the Office of National Statistics (ONS) and Quality Outcome Framework (QOF) sources. These included population density, %age >16, at fulltime work/education, %age over 60, %BME ethnicity, social deprivation as IMD2019, location as latitude/longitude, and patient engagement as %self-confident in their own long-term condition management. Average case morbidity was calculated. To provide a comparative measure of overall healthcare resource impact, individual GP practice impact scores were compared against the median practice. Results: The case incidence regression is a dynamic situation but it currently shows that Urban, %Working, and age >60 were the strongest determinants of case incidence. The local population comorbidity remains unchanged. The range of relative healthcare impact was wide with 80% of practices falling at 20%-250% of the national median. Once practice population numbers were included we found that the top 33% of GP practices supporting 45% of the patient population would require 68% of COVID-19 healthcare resources. The model provides useful information about the relative impact of Covid-19 on healthcare workload at GP practice granularity in all parts of England. Conclusion: Covid-19 is impacting on the utilisation of health/social care resources across the world. This model provides a way of predicting relative local levels of disease burden based on defined criteria, thereby providing a method for targeting limited care resources to optimise national/regional/local responses to the COVID-19 outbreak.

Eastern Boundary Upwelling Systems (EBUSs) are coastal hotspots of the potent greenhouse gas nitrous oxide (N2O). However, estimates of their emissions suffer from large uncertainties due to their significant spatial and temporal heterogeneity. Here, we derive the first multiyear, monthly resolution N2O emissions from three of the four major EBUSs using high-frequency coastal atmospheric measurements and an inverse method. We find average combined N2O emissions from the northern California, Benguela, and southern Canary upwelling systems to be 57.7 (51.4-63.9) Gg-N yr(-1). We also find an offshore region near the Benguela EBUS that exhibits large pulses of emissions with emissions that reach 677 Gg-N yr(-1) in 1 month. Our findings highlight that atmospheric measurements coupled with inverse modeling can capture the large variability in EBUS emissions by quantifying emissions over large spatial distances and over long time periods compared to previous methods using traditional oceanographic measurements. Plain Language Summary Eastern Boundary Upwelling Systems (EBUSs) are important emissions hotspots of marine nitrous oxide to the atmosphere, where it acts as a greenhouse gas and ozone depleting substance. Emissions from the EBUSs are highly episodic, and most previous estimates are snapshots derived from ship-based measurements. The variability in emissions combined with the sparsity of measurements makes EBUS emission estimates highly uncertain. Here, we use multiyear, near-continuous atmospheric measurements from coastal stations and an inverse modeling framework to derive emissions from three of the four major EBUSs. Our results quantify the significant spatial and temporal variability in emissions, which is not well-represented in global studies of marine nitrous oxide emissions.

Background: The COVID-19 pandemic has led to radical political control of social behaviour. The purpose of this paper is to explore data trends from the pandemic regarding infection rates/policy impact, and draw learning points for informing the unlocking process. Methods: The daily published cases in England in each of 149 Upper Tier Local Authority (UTLA) areas were converted to Average Daily Infection Rate (ADIR), an R-value - the number of further people infected by one infected person during their infectious phase with Rate of Change of Infection Rate (RCIR) also calculated. Stepwise regression was carried out to see what local factors could be linked to differences in local infection rates. Findings: By the 19th April 2020 the infection R has fallen from 2.8 on 23rd March before the lockdown and has stabilised at about 0.8, sufficient for suppression. However there remain significant variations between England regions. Regression analysis across UTLAs found that the only factor relating to reduction in ADIR was the historic number of confirmed number infection/000 population, There is however wide variation between Upper Tier Local Authorities (UTLA) areas. Extrapolation of these results showed that unreported community infection may be 150 times higher than reported cases, providing evidence that by the end of the second week in April, 26.8% of the population may already have had the disease and so have increased immunity. Extrapolation of these results showed that unreported community infection may be 150 times higher than reported cases, providing evidence that by the end of the second week in April, 26.8% of the population may already have had the disease and so have increased immunity.Interpretation: Analysis of current case data using infectious ratio has provided novel insight into the current national state and can be used to make better-informed decisions about future management of restricted social behaviour and movement.

ObjectivesOther than age, diabetes is the largest contributor to overall healthcare costs and reduced life expectancy in Europe. This paper aims to more exactly quantify the net impact of diabetes on different aspects of healthcare provision in hospitals in England, building on previous work that looked at the determinants of outcome in type 1 diabetes (T1DM) and type 2 diabetes (T2DM).SettingNHS Digital Hospital Episode Statistics (HES) in England was combined with the National Diabetes Audit (NDA) to provide the total number in practice of people with T1DM/T2DM.Outcome measuresWe compared differences between T1DM/T2DM and non-diabetes individuals in relation to hospital activity and associated cost.ResultsThe study captured 90% of hospital activity and £36 billion/year of hospital spend. The NDA Register showed that out of a total reported population of 58 million, 2.9 million (6.5%) had T2DM and 240 000 (0.6%) had T1DM. Bed-day analysis showed 17% of beds are occupied by T2DM and 3% by T1DM. The overall cost of hospital care for people with diabetes is £5.5 billion/year. Once the normally expected costs including the older age of T2DM hospital attenders are allowed for this fell to £3.0 billion/year or 8% of the total captured secondary care costs. This equates to £560/non-diabetes person compared with £3280/person with T1DM and £1686/person with T2DM. For people with diabetes, the net excess impact on non-elective/emergency work is £1.2 billion with additional estimated diabetes-related accident & emergency attendances at 440 000 costing the NHS £70 million/year. T1DM individuals required five times more secondary care support than non-diabetes individuals. T2DM individuals, even allowing for the age, require twice as much support as non-diabetes individuals.ConclusionsThis analysis shows that additional cost of provision of hospital services due to their diabetes comorbidities is £3 billion above that for non-diabetes, and that within this, T1DM has three times as much cost impact as T2DM. We suggest that supporting patients in diabetes management may significantly reduce hospital activity.

Background: Hypogonadism associates with increased cardiovascular morbidity/mortality in type 2 diabetes mellitus (T2DM)[1]. Increasing CAG repeat number within exon 1 of the androgen receptor gene associates with increased androgen receptor resistance/insulin resistance [2]. We here investigated the link between CAG repeat number and metabolic/cardiovascular outcomes in T2DM men. Methods: We determined in a 14-year follow-up cohort of 274 T2DM Caucasian men in Salford UK, the association between baseline androgen status/CAG repeat number (determined by PCR followed by Sequenom sequencing) and metabolic trajectory plus mortality. Results: Lower baseline testosterone was associated with higher Body Mass Index (BMI) (kg/m2) at 14-year follow-up: regression coefficient −0.30 (95% CI: −0.445 to −0.157), p = 0.0001 (total testosterone data) and higher HbA1c 2016. Higher baseline CAG repeat number associated with higher follow-up BMI in 2016 - each unit increase in CAG repeat associated with 0.43 increment in BMI 2016. At an average 14 year follow-up 55.8% of hypogonadal men had died vs 36.1% of eugonadal men (p = 0.001). 72% of deaths were from cardiovascular causes. There was a ‘u’ shaped relation between the number of CAG repeats and mortality such that 21–23 CAG repeats was associated with an up to 58% lower mortality rate than 23 CAG repeats (Figure 1). This was independent of baseline testosterone. Conclusion: A higher number of CAG repeats at the testosterone receptor gene associates with higher future BMI/increased HbA1c. There was a ‘u’ shaped relation between CAG repeat number and mortality rate. CAG repeat number may become part of cardiovascular risk assessment in T2DM men. Figure 1 CAG_cat Mortality Proportional mortality rate Lower bound Upper bound ≤20 40 43 32 53 21 12 24 13 39 22–23 28 50 36 64 >23 34 45 34 57

Overcoming bias due to confounding and missing data is challenging when analyzing observational data. Propensity scores are commonly used to account for the first problem and multiple imputation for the latter. Unfortunately, it is not known how best to proceed when both techniques are required. We investigate whether two different approaches to combining propensity scores and multiple imputation (Across and Within) lead to differences in the accuracy or precision of exposure effect estimates. Both approaches start by imputing missing values multiple times. Propensity scores are then estimated for each resulting dataset. Using the Across approach, the mean propensity score across imputations for each subject is used in a single subsequent analysis. Alternatively, the Within approach uses propensity scores individually to obtain exposure effect estimates in each imputation, which are combined to produce an overall estimate. These approaches were compared in a series of Monte Carlo simulations and applied to data from the British Society for Rheumatology Biologics Register. Results indicated that the Within approach produced unbiased estimates with appropriate confidence intervals, whereas the Across approach produced biased results and unrealistic confidence intervals. Researchers are encouraged to implement the Within approach when conducting propensity score analyses with incomplete data.

Summary Background Evidence of the comparative effectiveness of biological therapies for psoriasis on health‐related quality of life (HRQoL) in routine clinical practice is limited. Objectives To examine the comparative effectiveness of adalimumab, etanercept and ustekinumab on HRQoL in patients with psoriasis, and to identify potential predictors for improved HRQoL. Methods This was a prospective cohort study in which changes in HRQoL were assessed using the Dermatology Life Quality Index (DLQI) and EuroQoL‐5D (EQ‐5D) at 6 and 12 months. Multivariable regression models were developed to identify factors associated with achieving a DLQI of 0/1 and improvements in the EQ‐5D utility score. Results In total, 2152 patients with psoriasis were included, with 1239 patients on adalimumab, 517 on etanercept and 396 on ustekinumab; 81% were biologic naïve. For the entire cohort, the median (interquartile range) DLQI and EQ‐5D improved from 18 (13–24) and 0·73 (0·69–0·80) at baseline to 2 (0–7) and 0·85 (0·69–1·00) at 6 months, respectively (P < 0·001). Similar improvements were achieved at 12 months. At 12 months, multivariable regression modelling showed that female sex, multiple comorbidities, smoking and a higher DLQI or a lower EQ‐5D utility score at baseline predicted a lower likelihood of achieving a DLQI of 0/1 or improvement in the EQ‐5D. Compared with adalimumab, patients receiving etanercept, but not ustekinumab, were less likely to achieve a DLQI of 0/1. There was no significant difference between the biological therapies in EQ‐5D improvement. Conclusions In routine clinical practice biological therapies produce marked improvement in HRQoL, which is influenced by the choice of biological therapy, baseline impairment in HRQoL, lifestyle characteristics and comorbidities. These findings should help inform selection of optimal biological therapy for patients related to improvements in HRQoL., What's already known about this topic? Evidence of the comparative effectiveness of biological therapies for psoriasis on health‐related quality of life (HRQoL) in routine clinical practice is limited.Earlier observational studies were either cross‐sectional, thereby limiting the ability to compare changes in HRQoL, or cohort studies that have not taken into account important clinical factors that could influence treatment response, such as alterations in dosing regimens of biological therapies and the concomitant use of conventional systemic treatments for psoriasis. What does this study add? This large prospective cohort study found that in routine clinical practice, the use of biological therapies for psoriasis was associated with marked improvements in HRQoL over 12 months.These improvements were influenced by the choice of biological therapy, baseline impairment in HRQoL, lifestyle characteristics and comorbidities.Compared with adalimumab, patients receiving etanercept were less likely to achieve a DLQI of 0/1, but there was no significant difference between ustekinumab and adalimumab in the proportion of patients achieving a DLQI of 0/1.There was no significant difference between the three biological therapies in level of improvement in the EQ‐5D. Linked Comment: Finlay. Br J Dermatol 2017; 177:1164–1165.

The aims of the present study are to describe the characteristics of rheumatoid arthritis (RA) patients selected for tocilizumab (TCZ), compare the “real-world” effectiveness of TCZ and tumour necrosis factor inhibitors (TNFi) when used as a first biologic and assess the influence of past biologic exposure/concurrent methotrexate (MTX) therapy on post-TCZ treatment outcomes. The British Society for Rheumatology Biologics Register (BSRBR-RA) is a prospective cohort study following RA patients starting biologics in the UK. This includes patients starting TCZ as first or subsequent biologic, alongside biologic-naïve patients starting TNFi. Six-month disease activity and 1-year drug survival were compared between biologic-naïve patients starting TCZ versus TNFi and first-line versus subsequent TCZ users and TCZ users with MTX versus without using regression models adjusted by propensity score. Two hundred seventeen patients started TCZ, and 2419 started TNFi as first biologic. Seven hundred seventy-seven started TCZ after other biologics. First-line TCZ users had a higher prevalence of pulmonary fibrosis and cancer history than TNFi users. The first-line TCZ users were more likely to achieve DAS28 remission at 6 months than first-line TNFi, but other improvement markers were similar. The treatment response at 6 months was similar between subsequent-line TCZ users and first-line users after adjusting for baseline patient differences. Concurrent MTX use was not associated with treatment response in either first- or subsequent-line TCZ users. TCZ has been primarily used as subsequent-line biologic in the UK. When used as first line, the response appears similar to that observed in patients starting TNFi, suggesting that clinical response alone should not decide between initial biologic therapies. Electronic supplementary material The online version of this article (doi:10.1007/s10067-016-3485-5) contains supplementary material, which is available to authorized users.

Patients with chronic pain commonly believe their pain is related to the weather. Scientific evidence to support their beliefs is inconclusive, in part due to difficulties in getting a large dataset of patients frequently recording their pain symptoms during a variety of weather conditions. Smartphones allow the opportunity to collect data to overcome these difficulties. Our study Cloudy with a Chance of Pain analysed daily data from 2658 patients collected over a 15-month period. The analysis demonstrated significant yet modest relationships between pain and relative humidity, pressure and wind speed, with correlations remaining even when accounting for mood and physical activity. This research highlights how citizen-science experiments can collect large datasets on real-world populations to address long-standing health questions. These results will act as a starting point for a future system for patients to better manage their health through pain forecasts.

ObjectiveEvaluate relative clinical effectiveness of treatment options for type 2 diabetes mellitus (T2DM) using a statistical model of real-world evidence within UK general practitioner practices (GPP), to quantify the opportunities for diabetes care performance improvement.MethodFrom the National Diabetes Audit in 2015–2016 and 2016–2017, GPP target glycaemic control (TGC—%HbA1c ≤58 mmol/mol) and higher glycaemic risk (HGR —%HbA1c results >86 mmol/mol) outcomes were linked using multivariate linear regression to prescribing, demographics and practice service indicators. This was carried out both cross-sectionally (XS) (within year) and longitudinally (Lo) (across years) on 35 indicators. Standardised β coefficients were used to show relative level of impact of each factor. Improvement opportunity was calculated as impact on TGC & HGR numbers.ResultsValues from 6525 GPP with 2.7 million T2DM individuals were included. The cross-sectional model accounted for up to 28% TGC variance and 35% HGR variance, and the longitudinal model accounted for up to 9% TGC and 17% HGR variance. Practice service indicators including % achieving routine checks/blood pressure/cholesterol control targets were positively correlated, while demographic indicators including % younger age/social deprivation/white ethnicity were negatively correlated. The β values for selected molecules are shown as (increased TGC; decreased HGR), canagliflozin (XS 0.07;0.145/Lo 0.04;0.07), metformin (XS 0.12;0.04/Lo –;–), sitagliptin (XS 0.06;0.02/Lo 0.10;0.06), empagliflozin (XS–;0.07/Lo 0.09;0.07), dapagliflozin (XS –;0.04/Lo –;0.4), sulphonylurea (XS −0.18;−0.12/Lo–;–) and insulin (XS−0.14;0.02/ Lo−0.09;–). Moving all GPP prescribing and interventions to the equivalent of the top performing decile of GPP could result in total patients in TGC increasing from 1.90 million to 2.14 million, and total HGR falling from 191 000 to 123 000.ConclusionsGPP using more legacy therapies such as sulphonylurea/insulin demonstrate poorer outcomes, while those applying holistic patient management/use of newer molecules demonstrate improved glycaemic outcomes. If all GPP moved service levels/prescribing to those of the top decile, both TGC/HGR could be substantially improved.

One hydrochlorofluorocarbon and two hydrofluorocarbons (HCFC-22, HFC-125, and HFC-152a) were measured in air samples at the Cape Point observatory (CPT), South Africa, during 2017. These data represent the first such atmospheric measurements of these compounds from southwestern South Africa (SWSA). Baseline atmospheric growth rates were estimated to be 8.36, 4.10, and 0.71 ppt year-1 for HCFC-22, HFC-125, and HFC-152a, respectively. The CPT measurements were combined with an inverse model to investigate emissions from SWSA. For all three halocarbons, Cape Town was found to be the dominant source within SWSA. These estimates were extrapolated, based on population statistics, to estimate emissions for the whole of South Africa. We estimate South Africa's 2017 emissions to be 3.0 (1.6-4.4), 0.8 (0.5-1.2), and 1.1 (0.6-1.6) Gg year-1 for HCFC-22, HFC-125, and HFC-152a, respectively. For all three halocarbons, South Africa's contribution to global emissions is small (

Objectives To compare cervical screening attendance and cytology (high- and low-grade cervical dysplasia [HGCD and LGCD]) between women with RA and the English general population and between biologic DMARD (bDMARD)-naïve and exposed women. Methods The British Society for Rheumatology Biologics Register for RA (BSRBR-RA), a national prospective study of RA treatment outcomes, was linked to the National Health Service Cervical Screening Programme, providing data for 12 785 women to compare with national screening data. Rates of HGCD/LGCD were compared with rates of negative smears using risk difference calculations between BSRBR-RA and national statistics. Within the BSRBR-RA, coverage was compared between those with low and high physical disability scores, while coverage and cytology results were compared between bDMARD-naïve and -exposed RA patients. Results The mean 5 year screening coverage was significantly higher in BSRBR-RA (83%) compared with the general population (79%), but lower in women with high disability (78%) compared with lesser disability (85%). Risk differences for HGCD were lower in the BSRBR-RA compared with national statistics, whereas risk differences for LGCD were higher. There was no statistically significant difference in the rates of HGCD or LGCD between bDMARD-exposed and -naïve women. Conclusion This first-ever British analysis of cervical screening rates in RA has shown that women with RA have higher screening rates than the general population. Disability negatively impacts attendance, but treatment type does not. Women with RA did not have an increased risk of HGCD compared with national statistics, which was also not influenced by bDMARD exposure.

Summary Introduction Hypogonadism is more prevalent in men with type 2 diabetes (T2DM) (25%‐40%) than in men without T2DM. Hypogonadism has been associated with poorer glycaemic outcomes and increased cardiovascular morbidity/mortality. We report a 14‐year follow‐up study to evaluate the influence of baseline testosterone level on T2DM outcomes. Research design and methods A total of 550 men with T2DM underwent baseline total testosterone and dihydrotestosterone measurement by tandem mass spectrometry. Mean age of the men was 59.7 ± 12 (mean ± SD) years. Sex hormone‐binding globulin (SHBG) was measured and free testosterone estimated. Patients were followed up between 2002 and 2016. Mean follow‐up period was 12.2 ± 4 years using the Salford (UK) Integrated Health Records system. Results Mean baseline total testosterone was 13.7 ± 5.8 nmol/L, and mean free testosterone was 245.7 ± 88.0 pmol/L. Mean for low total testosterone (

The recovery of the stratospheric ozone layer relies on the continued decline in the atmospheric concentrations of ozone-depleting gases such as chlorofluorocarbons1. The atmospheric concentration of trichlorofluoromethane (CFC-11), the second-most abundant chlorofluorocarbon, has declined substantially since the mid-1990s2. A recently reported slowdown in the decline of the atmospheric concentration of CFC-11 after 2012, however, suggests that global emissions have increased3,4. A concurrent increase in CFC-11 emissions from eastern Asia contributes to the global emission increase, but the location and magnitude of this regional source are unknown3. Here, using high-frequency atmospheric observations from Gosan, South Korea, and Hateruma, Japan, together with global monitoring data and atmospheric chemical transport model simulations, we investigate regional CFC-11 emissions from eastern Asia. We show that emissions from eastern mainland China are 7.0 ± 3.0 (±1 standard deviation) gigagrams per year higher in 2014–2017 than in 2008–2012, and that the increase in emissions arises primarily around the northeastern provinces of Shandong and Hebei. This increase accounts for a substantial fraction (at least 40 to 60 per cent) of the global rise in CFC-11 emissions. We find no evidence for a significant increase in CFC-11 emissions from any other eastern Asian countries or other regions of the world where there are available data for the detection of regional emissions. The attribution of any remaining fraction of the global CFC-11 emission rise to other regions is limited by the sparsity of long-term measurements of sufficient frequency near potentially emissive regions. Several considerations suggest that the increase in CFC-11 emissions from eastern mainland China is likely to be the result of new production and use, which is inconsistent with the Montreal Protocol agreement to phase out global chlorofluorocarbon production by 2010. Emissions from eastern China account for approximately 40 to 60 per cent of the global rise in emissions of trichlorofluoromethane (CFC-11), which may be a result of new production and use.

Objectives.To determine whether the timing and duration of statin exposure following total hip/knee arthroplasty (THA/TKA) influence the risk of revision arthroplasty.Methods.Subjects from the Clinical Practice Research Datalink, a large population-based clinical database, who had THA/TKA from 1988 to 2016, were included. Propensity score adjusted Cox regression models were used to determine the association between statin exposure and the risk of revision THA/TKA, (1) at any time, and (2) if first exposed 0–1, 1–5, or > 5 years following THA/TKA. We also investigated the effect of duration of statin exposure (< 1, 1–2, 2–3, 3–4, 4–5, > 5 yrs).Results.The study included 151,305 participants. There were 65,032 (43%) exposed to statins during followup and 3500 (2.3%) had revision arthroplasty. In a propensity score adjusted model, exposure to statins was associated with a reduced risk of revision arthroplasty (HR 0.82, 95% CI 0.75–0.90). Participants first exposed within 1 year and between 1 and 5 years following THA/TKA (vs unexposed) had a reduced risk of revision arthroplasty (HR 0.82, 95% CI 0.74–0.91 and HR 0.76, 95% CI 0.65–0.90, respectively). In relation to duration of statin therapy, participants exposed for more than 5 years in total (vs < 1 yr) had a reduced risk of revision (HR 0.74, 95% CI 0.62–0.88).Conclusion.Statin therapy initiated up to 5 years following THA/TKA may reduce the risk of revision arthroplasty.

Summary Background Studies assessing cardiovascular disease (CVD) risk factors in patients with psoriasis have been limited by selection bias, inappropriate controls or a reliance on data collected for clinical reasons. Objectives To investigate whether screening for CVD risk factors in patients with psoriasis in primary care augments the known prevalence of CVD risk factors in a cross‐sectional study. Methods Patients listed as having psoriasis in primary care were recruited, screened and risk assessed by QRISK2. Results In total, 287 patients attended (mean age 53 years, 57% women, 94% white British, 22% severe disease, 33% self‐reported psoriatic arthritis). The proportion with known and screen‐detected (previously unknown) risk factors was as follows: hypertension 35% known and 13% screen‐detected; hypercholesterolaemia 32% and 37%; diabetes 6·6% and 3·1% and chronic kidney disease 1·1% and 4·5%. At least one screen‐detected risk factor was found in 48% and two or more risk factors were found in 21% of patients. One in three patients (37%) not previously known to be at high risk were found to have a high (> 10%) 10‐year CVD risk. Among the participants receiving treatment for known CVD risk factors, nearly half had suboptimal levels for blood pressure (46%) and cholesterol (46%). Conclusions Cardiovascular risk factor screening of primary care‐based adults with psoriasis identified a high proportion of patients (i) at high CVD risk, (ii) with screen‐detected risk factors and (iii) with suboptimally managed known risk factors. These findings need to be considered alongside reports that detected limited responses of clinicians to identified risk factors before universal CVD screening can be recommended., What's already known about this topic? Several studies have suggested that patients with psoriasis have a greater number of risk factors for cardiovascular disease (CVD) and a higher risk for vascular events compared with the general population.However, the prevalence data used to support systematic CVD risk factor screening in psoriasis have been limited by selection bias, inappropriate choice of control groups or reliance on risk factors measured for other clinical reasons. What does this study add? Cardiovascular risk factor screening of primary care‐based adults with psoriasis identified a high proportion of patients (i) at high CVD risk, (ii) with screen‐detected risk factors and (iii) with suboptimally managed known risk factors.These findings need to be considered alongside reports that detected limited responses of clinicians to identified risk factors before universal CVD screening can be recommended. Plain language summary available online

Carbon tetrachloride (CCl4) is an ozone-depleting substance, accounting for about 10% of the chlorine in the troposphere. Under the terms of the Montreal Protocol, its production for dispersive uses was banned from 2010. In this work we show that, despite the controls on production being introduced, CCl4 emissions from the eastern part of China did not decline between 2009 and 2016. This finding is in contrast to a recent bottom-up estimate, which predicted a significant decrease in emissions after the introduction of production controls. We find eastern Asian emissions of CCl4 to be 16 (9–24) Gg/year on average between 2009 and 2016, with the primary source regions being in eastern China. The spatial distribution of emissions that we derive suggests that the source distribution of CCl4 in China changed during the 8-year study period, indicating a new source or sources of emissions from China’s Shandong province after 2012., Plain Language Summary Carbon tetrachloride is one of several man-made gases that contribute to the depletion of the ozone layer high in the atmosphere. Because of this, restrictions were introduced on the use of this ozone-depleting substance, with the expectation that production should by now be close to 0. However, the slower than expected rate of decline of carbon tetrachloride in the atmosphere shows this is not the case, and a large portion of global emissions are unaccounted for. In this study we use atmospheric measurements of carbon tetrachloride from a site in East Asia to identify the magnitude and location of emissions from this region between 2009 and 2016. We find that there are significant ongoing emissions from eastern China and that these account for a large part of the missing emissions from global estimates. The presence of continued sources of this important ozone-depleting substance indicates that more could be done to speed up the recovery of the ozone layer.

Objective.In rheumatoid arthritis, composite outcomes constructed from a combination of outcome measures are widely used to enhance responsiveness (sensitivity to change) and comprehensively summarize response. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain is the primary outcome measure in many osteoarthritis (OA) trials. Information from other outcomes, such as rescue medication use and other WOMAC subscales, could be added to create composite outcomes, but the sensitivity of such a composite has not been tested.Methods.We used data from a completed trial of tanezumab for knee OA (NCT00733902). The WOMAC questionnaire and rescue medication use were measured at several timepoints, up to 16 weeks. Pain and rescue medication outcomes were standardized and combined into 3 composite outcomes through principal components analysis to produce 1 score (composite outcome) and their responsiveness was compared to WOMAC pain, the standard. We pooled all treatment doses of tanezumab into 1 treatment group, for simplicity, and compared this to the control group (placebo).Results.The composite outcomes showed modestly, but not statistically significantly greater responsiveness when compared to WOMAC pain alone. Adding information on rescue medication to the composite improved responsiveness. While improvements in sensitivity were modest, the required sample sizes for trials using composites was 20–40% less than trials using WOMAC pain alone.Conclusion.Combining information from related but distinct outcomes considered relevant to a particular treatment improved responsiveness, could reduce sample size requirements in OA trials, and might offer a way to better detect treatment efficacy in OA trials.

Importance: Patients with psoriasis enrolled in clinical trials of biologics may not be representative of the real-world population. There is evidence that patients ineligible for such trials have a greater risk of serious adverse events (SAEs), but the effect on drug discontinuation and effectiveness are unknown.Objective: To determine whether (1) drug discontinuation, (2) effectiveness, and (3) rates of SAEs differ in patients with psoriasis categorized as eligible or ineligible for clinical trials.Design, Setting, and Participants: An observational study using 157 dermatology centers in the United Kingdom and Republic of Ireland was carried out wherein we applied the eligibility criteria of clinical trials of biologic therapies for psoriasis to patients who were being followed up in the British Association of Dermatologists Biologic Interventions Register (BADBIR) and being prescribed biologics as part of standard clinical care. Patients with psoriasis registered to BADBIR who were taking etanercept (enbrel only; n = 1509), adalimumab (n = 4000), and ustekinumab (n = 1627) with at least 1 follow-up visit. Eligibility criteria were extracted from phase 3 licensing trials for etanercept, adalimumab, and ustekinumab for the treatment of moderate to severe psoriasis. Patients in BADBIR with a missing baseline Psoriasis Area and Severity Index (PASI) or baseline PASI value less than 10 (etanercept) or less than 12 (adalimumab; ustekinumab) but who would otherwise be eligible were investigated separately. Eligibility categories applied to BADBIR included: eligible, ineligible, insufficient baseline PASI only, and missing baseline PASI only.Main Outcomes and Measures: (1) Drug discontinuation: cumulative incidence at 12 months by stop reason per eligibility category and drug; (2) effectiveness: linear regression of absolute change in PASI from baseline to 6 and 12 months; and (3) SAEs: incidence rate ratio (IRR) at 12 months between eligibility categories per drug.Results: The mean (SD) age of the 7136 patients included in the analysis was 45 (13) years and 2924 (41%) were women and 4212 (59%) were men. Of 7136 patients, 839 (56%) etanercept, 2219 (56%) adalimumab, and 754 (46%) ustekinumab registrations were categorized as eligible. The most common reasons for ineligibility were diabetes (etanercept, 143 [9%]; ustekinumab, 201 [12%]) and nonchronic plaque psoriasis (adalimumab, 157 [4%]). Patients categorized as ineligible (etanercept, 367 [24%]; adalimumab, 282 [7%]; ustekinumab, 394 [24%]) achieved a smaller absolute change in PASI after 6 and 12 months (adalimumab, ustekinumab), and had significantly higher rates of SAEs compared with the eligible category (etanercept: IRR, 1.9; 95% CI, 1.4-2.6; adalimumab: IRR, 2.0; 95% CI, 1.5-2.6; ustekinumab: IRR, 2.8; 95% CI, 2.1-3.8). No significant differences in drug discontinuation were observed between categories.Conclusions and Relevance: Clinical trial effectiveness and safety outcomes are not representative of real-world patients in BADBIR patients categorized as ineligible for such trials.

Objectives: Our aim was to describe the burden of early dcSSc in terms of disability, fatigue and pain in the European Scleroderma Observational Study cohort, and to explore associated clinical features.Methods: Patients completed questionnaires at study entry, 12 and 24 months, including the HAQ disability index (HAQ-DI), the Cochin Hand Function Scale (CHFS), the Functional Assessment of Chronic Illness Therapy-fatigue and the Short Form 36 (SF36). Associates examined included the modified Rodnan skin score (mRSS), current digital ulcers and internal organ involvement. Correlations between 12-month changes were also examined.Results: The 326 patients recruited (median disease duration 11.9 months) displayed high levels of disability [mean (S.D.) HAQ-DI 1.1 (0.83)], with ‘grip’ and ‘activity’ being most affected. Of the 18 activities assessed in the CHFS, those involving fine finger movements were most affected. High HAQ-DI and CHFS scores were both associated with high mRSS (ρ = 0.34, P < 0.0001 and ρ = 0.35, P < 0.0001, respectively). HAQ-DI was higher in patients with digital ulcers (P = 0.004), pulmonary fibrosis (P = 0.005), cardiac (P = 0.005) and muscle involvement (P = 0.002). As anticipated, HAQ-DI, CHFS, the Functional Assessment of Chronic Illness Therapy and SF36 scores were all highly correlated, in particular the HAQ-DI with the CHFS (ρ = 0.84, P < 0.0001). Worsening HAQ-DI over 12 months was strongly associated with increasing mRSS (ρ = 0.40, P < 0.0001), decreasing hand function (ρ = 0.57, P < 0.0001) and increasing fatigue (ρ = −0.53, P < 0.0001).Conclusion: The European Scleroderma Observational Study highlights the burden of disability in early dcSSc, with high levels of disability and fatigue, associating with the degree of skin thickening (mRSS). Impaired hand function is a major contributor to overall disability.

Aims/hypothesis The aim of this study was to determine whether social deprivation in the presence of diabetes is an independent predictor of developing a foot ulcer and separately of mortality. Methods This was a primary-care-based retrospective analysis of 13,955 adults with type 1 (n = 1370) or type 2 (n = 12,585) diabetes after a median follow-up of 10.5 years. Demographic characteristics, indices of social deprivation and clinical variables were assessed at baseline. The primary outcomes were new foot ulceration (in those without a previous history of foot ulcers) and all-cause mortality. Cox proportional hazard models were used to describe the associations among foot ulceration, social deprivation and mortality. Results The mean age of the population was 69.4 (range: 16–89) years. The incidence of foot ulceration was greater in individuals with type 2 (8.6%) compared with type 1 diabetes (4.8%). Occurrence was similar by sex, but increased with age and deprivation index. Individuals in the highest quintile of deprivation were 77% more likely to develop a foot ulcer compared with those in the lowest quintile (OR 1.77 [95% CI 1.45, 2.14], p