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

Non-linear operations in quantum information theory

Quantum information theory is used to analize various non-linear operations on quantum states. The universal disentanglement machine is shown to be impossible, and partial (negative) results are obtained in the state-dependent case. The efficiency of the transformation of non-orthogonal states into orthogonal ones is discussed.Comment: 11 pages, LaTeX, 3 figures on separate page

Biologic treatments (other than anti-TNF therapy) licensed for use in rheumatoid arthritis

Despite the huge progress made by the use of tumour necrosis factor (TNF) inhibitors in the treatment of rheumatoid arthritis (RA), there was still an unmet need for discovering and implementing new biologic therapies for RA patients who lost response or had side-effects to TNF inhibitors. The advances in molecular biology and understanding of the complex pathogenesis of RA enabled the identification of other pivotal molecules, whose blockage was associated with clinical benefits in RA. This chapter reviews the clinical efficacy, safety profile and cost-effectiveness of several biologic agents licensed for use in RA patients, which target different interleukins (IL), such as IL1 (anakinra) and IL6 (tocilizumab), or are associated with B cell depletion (rituximab), T cell co-stimulatory blockage (abatacept) and small molecule inhibition (tofacitinib). In addition, we discuss the national and international guidelines for use of these biologic agents in relation to the use of TNF inhibitors in patients with moderatesevere RA, providing examples of switching between various biologic therapies

The use of real-world data to address questions of patient safety

Pharmacovigilance registries of biologics were established to evaluate the risk of adverse events that may be missed in trials due to shorter durations and homogeneous samples. This review will present the strengths and weaknesses of registry data in addressing patient safety issues. Since their inception, scope has broadened because registries represent a relatively inexpensive approach to answering many clinical questions, both research and non-research focused. They achieve high statistical power, allow direct comparability, and offer a level of detail about adverse events not possible with trial data. Registries have been central in clarifying the risk of infection and malignancy with anti-TNF therapy, despite the limitations of selection and channelling bias, incomplete case capture, unmeasured confounding, and the inability to infer causality. Routinely collected data from electronic health records and national audits offer alternative real-world resources, further assisting patients and clinicians in understanding the risks of biologic therapy choices.</p

New biologic agents and biosimilars developed for rheumatoid arthritis

The pathogenesis of rheumatoid arthritis (RA) is characterised by interactions between several types of immune cells, which are associated with the release of multiple inflammatory cytokines. Recently, numerous biologic treatments targeting classes of immune cells, cytokines or intra-cellular pathways of pro-inflammatory signals have been developed. Some of them are currently under research as potential therapeutic options for RA patients. This chapter reviews the available evidence regarding the safety and efficacy of new biologic agents targeting B cells, proinflammatory interleukins (IL), T helper 17 (Th17) pathway and intracellular enzymes. This chapter reviews the most relevant randomised controlled trials (RCTs) which have proven the efficacy of different biologic agents and small molecule inhibitors in controlling the inflammation associated with RA. The management of RA remains a dynamic and evolving field. The development of less expensive ‘biosimilar’ drugs, analogous to existing licensed biologic therapies, is an emerging area of research that deserves particular attention

Entanglement, local measurements, and symmetry

A definition of entanglement in terms of local measurements is discussed. Viz, the maximum entanglement corresponds to the states that cause the highest level of quantum fluctuations in all local measurements determined by the dynamic symmetry group of the system. A number of examples illustrating this definition is considered.Comment: 10 pages. to be published in Journal of Optics

Tumour necrosis factor inhibitors used in the treatment of rheumatoid arthritis: Evidence of safety, efficacy and health implication

Rheumatoid arthritis (RA) is a systemic autoimmune condition characterised by inflammation and destruction of synovial joints. The pathogenesis of inflammation is underpinned by interaction and activation of immune cells, which release inflammatory cytokines such as tumour necrosis factor (TNF) and interleukins. These mechanisms of disease pathogenesis were targeted by specific drugs in the form of monoclonal antibodies (mAb) or soluble receptors. The advent of biological disease modifying therapies (bDMARDs) has revolutionised the management of RA. These agents dramatically reduce synovial inflammation, halt the progression of radiographic joint damage, and improve functional ability and health related quality of life outcomes. This has a positive impact on the socioeconomic burden of RA. This chapter reviews the pathogenesis of RA and evidence behind the use of TNF inhibitors licensed for RA treatment. We focus on clinical efficacy, safety profile and cost-effectiveness of infliximab, etanercept, adalimumab, certolizumab, golimumab. Additionally, we discuss national and international recommendations for the clinical use of TNF inhibitors, with further consideration of the financial implications. Examples of clinical randomised controlled trials (RCTs), which have proven the efficacy of different TNF inhibitors in RA are also included in this chapter. The use of TNF inhibitor biosimilars will be discussed in chapter 11

A Systematic Review and Meta-Analysis of Anti-Rheumatic Drugs and Vaccine Immunogenicity in Rheumatoid Arthritis

Objectives: Vaccination is a key strategy to reduce infection risk in RA patients and is advocated in internationally recognised rheumatology society guidelines. The aim was to evaluate to the impact of anti-rheumatic drugs on influenza and pneumococcal vaccine immunogenicity.Methods: We conducted a systematic literature review and meta-analysis comparing the humoral response to influenza (pandemic and seasonal trivalent subunitvaccines) and pneumococcal (PPV23, PCV-7, PCV-13) vaccination in adult RA patients treated with anti-rheumatic drugs. Vaccine immunogenicity was assessed byseroprotection rates measured 3 to 6-weeks post immunisation. Risk ratios and 95% CIs were pooled.Results: Nine studies were included in the meta-analysis (7 studies investigating anti-rheumatic drug exposures and influenza humoral response, 2 studiesinvestigating pneumococcal vaccine response). Influenza vaccine responses to all subunit strains (H1N1, H3N2, B strain) were preserved with methotrexate and TNFinhibitor drug exposure. Methotrexate but not TNF inhibitor drug exposure was associated with reduced 6B and 23F serotype pneumococcal vaccine response (riskratio 0.42, 95% CI 0.28 to 0.63) vs. 0.98 (95% CI 0.58 to 1,67)), however limited data were available to draw any firm conclusions. Combination of methotrexate withtocilizumab or tofacitinib was associated with reduced pneumococcal and influenza vaccine responses.Conclusions: Anti-rheumatic drugs may negatively impact humoral responses to vaccination as evidenced by pneumococcal responses with methotrexate exposure,however they are safe and should not preclude immunisation against vaccine preventable disease. Vaccination should be considered in all RA patients andencouraged as part of routine care. Systematic review registration number: PROSPERO 2016: CRD42016048093