An algorithm to identify rheumatoid arthritis in primary care: a Clinical Practice Research Datalink study

Objective: Rheumatoid arthritis (RA) is a multisystem, inflammatory disorder associated with increased levels of morbidity and mortality. While much research into the condition is conducted in the secondary care setting, routinely collected primary care databases provide an important source of research data. This study aimed to update an algorithm to define RA that was previously developed and validated in the General Practice Research Database (GPRD). Methods: The original algorithm consisted of two criteria. Individuals meeting at least one were considered to have RA. Criterion 1:≥1 RA Read code and a disease modifying antirheumatic drug (DMARD) without an alternative indication. Criterion 2:≥2RA Read codes, with at least one 'strong' code and no alternative diagnoses. Lists of codes for consultations and prescriptions were obtained from the authors of the original algorithm where these were available, or compiled based on the original description and clinical knowledge. 4161 people with a first Read code for RA between 1 January 2010 and 31 December 2012 were selected from the Clinical Practice Research Datalink (CPRD, successor to the GPRD), and the criteria applied. Results: Code lists were updated for the introduction of new Read codes and biological DMARDs. 3577/ 4161 (86%) of people met the updated algorithm for RA, compared to 61% in the original development study. 62.8% of people fulfilled both Criterion 1 and Criterion 2. Conclusions: Those wishing to define RA in the CPRD, should consider using this updated algorithm, rather than a single RA code, if they wish to identify only those who are most likely to have RA

Is cancer associated with polymyalgia rheumatica?: A cohort study in the General Practice Research Database

OBJECTIVE: To investigate the incidence of new cancer diagnoses in a community sample of patients with polymyalgia rheumatica (PMR). METHODS: All incident cases of PMR in the UK General Practice Research Database (GPRD) (1987-99), without pre-existing cancer or vascular disease and treated with corticosteroids (n=2877) were matched with up to five age, sex and GP practice patients without PMR (n=9942). Participants were followed up until first cancer diagnosis, death, transfer out of the database or end of available records. RESULTS: The mean age of the sample was 71.6 years (SD 9.0), 73% were female. Median follow-up time was 7.8 years (IQR 3.4, 12.3). 667 (23.2%) people with a PMR diagnosis developed cancer compared with 1938 (19.5%) of those without PMR. There was an interaction between PMR status and time. In the first 6 months after diagnosis, those with a PMR diagnosis were significantly more likely to receive a cancer diagnosis (adjusted HR (95% CI): 1.69 (1.18 to 2.42)). The number of events was small, but occurrences of prostate, blood, lymph nodes, female reproductive and nervous system cancers may be more common in those with PMR in the first 6 months after PMR diagnosis. CONCLUSIONS: An increase in the rate of cancer diagnoses was noted in the first 6 months of observation, but we were unable to determine whether the cancer incidence in PMR was different from controls, beyond this time point. Clinicians should ensure they fully exclude cancer as a cause of PMR-like symptoms and monitor patients for possible malignancies

Prevalence of cardiovascular-related comorbidity in ankylosing spondylitis, psoriatic arthritis and psoriasis in primary care: a matched retrospective cohort study

The aim of this study is to compare the prevalence of cardiovascular (CVD)-related comorbidities in patients with ankylosing spondylitis (AS), psoriatic arthritis (PsA) or psoriasis (Ps) in UK primary care against matched cohorts. Matched retrospective cohort study used a primary care consultation database. Three cohorts were constructed using all patients with a Read code diagnosis of AS, PsA or Ps between 1999 and 2009; each cohort was then compared in a 1:4 ratio to a matched cohort. The prevalence of CVD-related comorbidities (hypertension, ischaemic heart disease, hyperlipidaemia and diabetes mellitus) were identified by the first consultation of a comorbid Read code, in those with an inflammatory condition of interest. The prevalence of CVD-related comorbidities was compared between each inflammatory cohort and their matched cohort using Fisher’s exact test. Ninety-four AS, 106 PsA and 290 Ps patients were identified. Compared with matched cohorts, the most prevalent CVD-related comorbidity in patients with AS was hypertension (35 (37.2 %) vs. 96 matched (25.5 %), p = 0.03); this was also the case for PsA (41 (38.7 %) vs. 114 matched (26.9 %), p = 0.02). No differences were seen in the prevalence of other CVD-related comorbidities in those with AS, PsA or Ps compared to their matched cohorts. Our findings provide UK comparisons of CVD-related comorbidities in patients with AS, PsA and Ps alone; specifically, demonstrating increased prevalence of hypertension in AS and PsA cohorts compared to their matched cohorts. This further supports the argument for more evidence in the need for screening and intervention around CVD comorbidities in inflammatory conditions

Characterising those with incident polymyalgia rheumatica in primary care: results from the PMR Cohort Study.

BACKGROUND: The aim was to characterise the sociodemographic, general health and polymyalgia rheumatica (PMR)-specific features of participants in a large inception cohort of patients with PMR diagnosed in UK primary care. METHODS: Patients (n = 739) with a new diagnosis of PMR were referred into the study and mailed a questionnaire detailing their general health and sociodemographic characteristics in addition to the symptoms of and treatment for PMR. Characteristics of responders and non-responders were compared and descriptive statistics were used to characterise the health of the cohort. RESULTS: A total of 654 individuals responded to the questionnaire (adjusted response 90.1 %). Responders and non-responders were similar in age, gender and deprivation (based on postcode). The mean (standard deviation) age of the recruited cohort was 72.4 (9.3) years; 62.2 % were female. The sample reported high levels of pain and stiffness (8 out of 10 on numerical rating scales) and reported stiffness that lasted throughout the day. High levels of functional impairment, fatigue, insomnia and polypharmacy were also reported. Overall, women reported worse general and PMR-specific health than did men. CONCLUSIONS: This first primary care cohort of patients with incident PMR is similar in demographic terms to cohorts recruited in secondary care. However, the extent of symptoms, particularly reported stiffness, is higher than has been described previously. Given the majority of patients with PMR are exclusively managed in primary care, this cohort provides important information on the course of PMR in the community that will help clinicians managing this painful and disabling condition

The INCLUDE study: INtegrating and improving Care for patients with infLammatory rheUmatological DisordErs in the community; identifying multimorbidity: Protocol for a pilot randomized controlled trial.

Background: Patients with inflammatory rheumatic conditions such as rheumatoid arthritis, polymyalgia rheumatica and ankylosing spondylitis are at increased risk of common comorbidities such as cardiovascular disease, osteoporosis and anxiety and depression which lead to increased morbidity and mortality. These associated morbidities are often un-recognized and under-treated. While patients with other long-term conditions such as diabetes are invited for routine reviews in primary care, which may include identification and management of co-morbidities, at present this does not occur for patients with inflammatory conditions, and thus, opportunities to diagnose and optimally manage these comorbidities are missed. Objective: To evaluate the feasibility and acceptability of a nurse-led integrated care review (the INtegrating and improving Care for patients with infLammatory rheUmatological DisordErs in the community (INCLUDE) review) for people with inflammatory rheumatological conditions in primary care. Design: A pilot cluster randomized controlled trial will be undertaken to test the feasibility and acceptability of a nurse-led integrated primary care review for identification, assessment and initial management of common comorbidities including cardiovascular disease, osteoporosis and anxiety and depression. A process evaluation will be undertaken using a mixed methods approach including participant self-reported questionnaires, a medical record review, an INCLUDE EMIS template, intervention fidelity checking using audio-recordings of the INCLUDE review consultation and qualitative interviews with patient participants, study nurses and study general practitioners (GPs). Discussion: Success of the pilot study will be measured against the engagement, recruitment and study retention rates of both general practices and participants. Acceptability of the INCLUDE review to patients and practitioners and treatment fidelity will be explored using a parallel process evaluation. Trial Registration: ISRCTN12765345

Molecular Characterization of Circulating Microbiome Signatures in Rheumatoid Arthritis

Rheumatoid Arthritis (RA) has been increasingly associated with perturbations to the microbial communities that reside in and on the body (the microbiome), in both human and animal studies. To date, such studies have mainly focused on the microbial communities that inhabit the gut and oral cavity. Mounting evidence suggests that microbial DNA can be detected in the blood circulation using a range of molecular methods. This DNA may represent an untapped pool of biomarkers that have the potential to report on changes to the microbiome of distant sites (e.g., example, the gut and oral cavity). To this end, through amplification and sequencing of the bacterial 16S rRNA variable region four, we evaluated the presence and identity of microbial DNA in blood samples obtained from RA patients (both prior to and 3 months following the instigation of treatment) in comparison to a small number of healthy control subjects and samples obtained from patients with ankylosing spondylitis (AS) and psoriatic arthritis (PA). Bacterial-derived DNA was identified in the majority of our patient samples. Taxonomic classification revealed that the microbiome community in RA was distinct from AS, PA, and the healthy state. Through analysis of paired patient samples obtained prior to and 3 months following treatment (V0 vs. V3), we found the microbiome to be modulated by treatment, and in many cases, this shift reduced the distance between these samples and the healthy control samples, suggesting a partial normalization following treatment in some patients. This effect was especially evident in seronegative arthritis patients. Herein, we provide further evidence for the existence of a blood microbiome in health and identify specific taxa modulated in disease and following treatment. These blood-derived signatures may have significant utility as disease biomarkers and suggest this area warrants further investigation