Data quality predicts care quality: findings from a national clinical audit

Background: Missing clinical outcome data are a common occurrence in longitudinal studies. Data quality in clinical audit is a particular cause for concern. The relationship between departmental levels of missing clinical outcome data and care quality is not known. We hypothesise that completeness of key outcome data in a national audit predicts departmental performance. Methods: The National Clinical Audit for Rheumatoid and Early Inflammatory Arthritis (NCAREIA) collected data on care of patients with suspected rheumatoid arthritis (RA) from early 2014 to late 2015. This observational cohort study collected data on patient demographics, departmental variables, service quality measures including time to treatment, and the key RA clinical outcome measure, disease activity at baseline, and 3 months follow-up. A mixed effects model was conducted to identify departments with high/low proportions of missing baseline disease activity data with the results plotted on a caterpillar graph. A mixed effects model was conducted to assess if missing baseline disease activity predicted prompt treatment. Results: Six thousand two hundred five patients with complete treatment time data and a diagnosis of RA were recruited from 136 departments. 34.3% had missing disease activity at baseline. Mixed effects modelling identified 13 departments with high levels of missing disease activity, with a cluster observed in the Northwest of England. Missing baseline disease activity was associated with not commencing treatment promptly in an adjusted mix effects model, odds ratio 0.50 (95% CI 0.41 to 0.61, p < 0.0001). Conclusions: We have shown that poor engagement in a national audit program correlates with the quality of care provided. Our findings support the use of data completeness as an additional service quality indicator

A Comparison of Stride Length and Lower Extremity Kinematics during Barefoot and Shod Running in Well Trained Distance Runners

Stride length, hip, knee and ankle angles were compared during barefoot and shod running on a treadmill at two speeds. Nine well-trained (1500m time: 3min:59.80s ± 14.7 s) male (22 ±3 years; 73 ±9 kg; 1.79 ±0.4 m) middle distance (800 m – 5,000 m) runners performed 2 minutes of running at 3.05 m·s-1 and 4.72 m·s-1 on an treadmill. This approach allowed continuous measurement of lower extremity kinematic data and calculation of stride length. Statistical analysis using a 2X2 factorial ANOVA revealed speed to have a main effect on stride length and hip angle and footwear to have a main effect on hip angle. There was a significant speed*footwear interaction for knee and ankle angles. Compared to shod running at the lower speed (3.05 m·s-1), well trained runners have greater hip, knee and ankle angles when running barefoot. Runners undertake a high volume (~75%) of training at lower intensities and therefore knowledge of how barefoot running alters running kinematics at low and high speeds may be useful to the runner

Experimental demonstration of quantum effects in the operation of microscopic heat engines

The heat engine, a machine that extracts useful work from thermal sources, is one of the basic theoretical constructs and fundamental applications of classical thermodynamics. The classical description of a heat engine does not include coherence in its microscopic degrees of freedom. By contrast, a quantum heat engine might possess coherence between its internal states. Although the Carnot efficiency cannot be surpassed, and coherence can be performance degrading in certain conditions, it was recently predicted that even when using only thermal resources, internal coherence can enable a quantum heat engine to produce more power than any classical heat engine using the same resources. Such a power boost therefore constitutes a quantum thermodynamic signature. It has also been shown that the presence of coherence results in the thermodynamic equivalence of different quantum heat engine types, an effect with no classical counterpart. Microscopic heat machines have been recently implemented with trapped ions, and proposals for heat machines using superconducting circuits and optomechanics have been made. When operated with standard thermal baths, however, the machines implemented so far have not demonstrated any inherently quantum feature in their thermodynamic quantities. Here we implement two types of quantum heat engines by use of an ensemble of nitrogen-vacancy centres in diamond, and experimentally demonstrate both the coherence power boost and the equivalence of different heat-engine types. This constitutes the first observation of quantum thermodynamic signatures in heat machines

Occupational impacts of early inflammatory arthritis : results from the National Early Inflammatory Arthritis Audit

Peer reviewe

Variation and implications of treatment decisions in early rheumatoid arthritis: results from a nationwide cohort study

Objectives Trial data have provided an evidence base to guide early treatment in RA. Few studies have investigated rheumatologists’ adherence to guidelines, and subsequent impact on outcomes. The objectives of this study are to characterize baseline prescribing for patients with RA across the National Health Service, identifying treatment decisions that associate with patient outcomes. Methods A nationwide audit of RA collected information on treatment choices, DAS and sociodemographic factors at baseline. Treatment response was assessed at 3 months. Multilevel regression models were used to characterize departmental variations in prescribing. Heat maps were used to visualize geographical variation. Mixed effects regression models were constructed to assess the relationship between treatment decisions and disease outcomes, adjusting for patient and department level covariates. Results A total of 7154 patients with a diagnosis of RA were recruited from 136 departments. There was broad variation in prescribing choices, even between departments close to one another, with evidence of substantial deviation from guidelines. Over 75% of patients received glucocorticoids, fewer than half received combination conventional DMARDs. Early glucocorticoid therapy associated with achieving a good treatment response [odds ratio 1.93 (95% CI 1.31, 2.84), P-value = 0.001]. The association was maintained following propensity modelling and imputation. Conclusion Guideline adherence varies between departments and cannot be explained by case-mix alone. Departments that prescribe early adjunctive steroid achieve better short-term outcomes. Further research should work to ensure that the early arthritis evidence base translates into better outcomes for patients

Diagnostic delay is common for patients with axial spondyloarthritis: Results from the National Early Inflammatory Arthritis Audit

OBJECTIVES: Updated guidelines for patients with axial SpA (axSpA) have sought to reduce diagnostic delay by raising awareness among clinicians. We used the National Early Inflammatory Arthritis Audit (NEIAA) to describe baseline characteristics and time to diagnosis for newly referred patients with axSpA in England and Wales. METHODS: Analyses were performed on sociodemographic and clinical metrics, including time to referral and assessment, for axSpA patients (n = 784) recruited to the NEIAA between May 2018 and March 2020. Comparators were patients recruited to the NEIAA with RA (n = 9270) or mechanical back pain (MBP; n = 370) in the same period. RESULTS: Symptom duration prior to initial rheumatology assessment was longer in axSpA than RA patients (P 6 months, compared with 33.7% of RA patients and 76.0% of MBP patients. Following referral, the median time to initial rheumatology assessment was longer for axSpA than RA patients (36 vs 24 days; P < 0.001) and similar to MBP patients (39 days; P = 0.30). Of the subset of patients deemed eligible for early inflammatory arthritis pathway follow-up, fewer axSpA than RA patients had disease education provided (77.5% vs 97.8%) and RA patients reported a better understanding of their condition and treatment. CONCLUSION: Diagnostic delay in axSpA remains a major challenge despite improved disease understanding and updated referral guidelines. Disease education is provided to fewer axSpA than RA patients, highlighting the need for specialist clinics and support programmes for axSpA patients

Gout incidence and management during the COVID-19 pandemic in England, UK: a nationwide observational study using OpenSAFELY

BackgroundGout is the most prevalent inflammatory arthritis, yet one of the worst managed. Our objective was to assess how the COVID-19 pandemic impacted incidence and quality of care for people with gout in England, UK.MethodsWith the approval of National Health Service England, we did a population-level cohort study using primary care and hospital electronic health record data for 17·9 million adults registered with general practices using TPP health record software, via the OpenSAFELY platform. The study period was from March 1, 2015, to Feb 28, 2023. Individuals aged 18–110 years were defined as having incident gout if they were assigned index diagnostic codes for gout, were registered with TPP practices in England for at least 12 months before diagnosis, did not receive prescriptions for urate-lowering therapy more than 30 days before diagnosis, and had not been admitted to hospital or attended an emergency department for gout flares more than 30 days before diagnosis. Outcomes assessed were incidence and prevalence of people with recorded gout diagnoses, incidence of gout hospitalisations, initiation of urate-lowering therapy, and attainment of serum urate targets (≤360 μmol/L).FindingsFrom a reference population of 17 865 145 adults, 246 695 individuals were diagnosed with incident gout. The mean age of individuals with incident gout was 61·3 years (SD 16·2). 66 265 (26·9%) of 246 695 individuals were female, 180 430 (73·1%) were male, and 189 035 (90·9%) of 208 050 individuals with available ethnicity data were White. Incident gout diagnoses decreased by 30·9% in the year beginning March, 2020, compared with the preceding year (1·23 diagnoses vs 1·78 diagnoses per 1000 adults). Gout prevalence was 3·07% in 2015–16, and 3·21% in 2022–23. Gout hospitalisations decreased by 30·1% in the year commencing March, 2020, compared with the preceding year (9·6 admissions vs 13·7 admissions per 100 000 adults). Of 228 095 people with incident gout and available follow-up, 66 560 (29·2%) were prescribed urate-lowering therapy within 6 months. Of 65 305 individuals who initiated urate-lowering therapy with available follow-up, 16 790 (25·7%) attained a serum urate concentration of 360 μmol/L or less within 6 months of urate-lowering therapy initiation. In interrupted time-series analyses, urate-lowering therapy prescribing improved modestly during the pandemic, compared with pre-pandemic, whereas urate target attainment was similar.InterpretationUsing gout as an exemplar disease, we showed the complexity of how health care was impacted during the COVID-19 pandemic. We observed a reduction in gout diagnoses but no effect on treatment metrics. We showed how country-wide, routinely collected data can be used to map disease epidemiology and monitor care quality

Clinical Utility of Random Anti–Tumor Necrosis Factor Drug–Level Testing and Measurement of Antidrug Antibodies on the Long-Term Treatment Response in Rheumatoid Arthritis

Objective: To investigate whether antidrug antibodies and/or drug non-trough levels predict the long-term treatment response in a large cohort of patients with rheumatoid arthritis (RA) treated with adalimumab or etanercept and to identify factors influencing antidrug antibody and drug levels to optimize future treatment decisions.  Methods: A total of 331 patients from an observational prospective cohort were selected (160 patients treated with adalimumab and 171 treated with etanercept). Antidrug antibody levels were measured by radioimmunoassay, and drug levels were measured by enzyme-linked immunosorbent assay in 835 serial serum samples obtained 3, 6, and 12 months after initiation of therapy. The association between antidrug antibodies and drug non-trough levels and the treatment response (change in the Disease Activity Score in 28 joints) was evaluated.  Results: Among patients who completed 12 months of followup, antidrug antibodies were detected in 24.8% of those receiving adalimumab (31 of 125) and in none of those receiving etanercept. At 3 months, antidrug antibody formation and low adalimumab levels were significant predictors of no response according to the European League Against Rheumatism (EULAR) criteria at 12 months (area under the receiver operating characteristic curve 0.71 [95% confidence interval (95% CI) 0.57, 0.85]). Antidrug antibody–positive patients received lower median dosages of methotrexate compared with antidrug antibody–negative patients (15 mg/week versus 20 mg/week; P = 0.01) and had a longer disease duration (14.0 versus 7.7 years; P = 0.03). The adalimumab level was the best predictor of change in the DAS28 at 12 months, after adjustment for confounders (regression coefficient 0.060 [95% CI 0.015, 0.10], P = 0.009). Etanercept levels were associated with the EULAR response at 12 months (regression coefficient 0.088 [95% CI 0.019, 0.16], P = 0.012); however, this difference was not significant after adjustment. A body mass index of ≥30 kg/m2 and poor adherence were associated with lower drug levels.  Conclusion: Pharmacologic testing in anti–tumor necrosis factor–treated patients is clinically useful even in the absence of trough levels. At 3 months, antidrug antibodies and low adalimumab levels are significant predictors of no response according to the EULAR criteria at 12 months

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes