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

Evaluating on-line health information for patients with polymyalgia rheumatica: a descriptive study

BACKGROUND: The Internet is increasingly used to access health information, although the quality of information varies. The aim of this study was to evaluate the readability, and quality of websites about polymyalgia rheumatica (PMR). METHODS: Three UK search engines (Google, Yahoo and Bing) were searched for the term 'polymyalgia rheumatica'. After deleting duplicates, the first 50 eligible websites from each were evaluated. Readability was assessed using the Flesch Reading Ease and 'Simple Measure of Gobbledygook (SMOG) Readability' indicators. Credibility was assessed using a previously published Credibility Indicator. RESULTS: Of the 52 unique websites identified, the mean (standard deviation) Flesch Reading Ease and SMOG Readability scores were 48 (15) and 10 (2), respectively. The mean (SD) Credibility Indicator was 2 (1). Fifty (96%) of websites were accurate. Website design and content was good, with an average of 68 and 64% respectively, of the assessed criteria being met. CONCLUSIONS: Most websites about PMR require a higher readability age than is recommended. Thus whilst websites are often well designed and accurate this study suggests that their content could be refined and simplified to maximise patient benefit

Improving recognition of anxiety and depression in rheumatoid arthritis: a qualitative study in a community clinic.

BACKGROUND: Comorbid anxiety and depression are common in patients with rheumatoid arthritis (RA) but are often under-recognised and treated, contributing to worse outcomes. National Institute for Health and Care Excellence (NICE) recommends that patients with RA should be offered a holistic annual review, including an assessment of mood. AIM: To explore patients' perspectives of anxiety and depression in RA and preferences for disclosure and management of mood problems. DESIGN AND SETTING: Qualitative interview study with patients recruited from a nurse-led RA annual review clinic in the Midlands, England. METHOD: Patients attending the clinic who scored ≥3 on the case-finding questions (PHQ-2 and GAD-2) were invited for interview. Data were analysed thematically using principles of constant comparison. RESULTS: Participants recognised a connection between their RA and mood, though this was perceived variably. Some lacked candidacy for care, normalising their mood problems. Fear of stigmatisation, a lack of time, and the perception that clinicians prioritise physical over mental health problems recursively affected help-seeking. Good communication and continuity of care were perceived to be integral to disclosure of mood problems. Participants expressed a preference for psychological therapies, though they reported problems accessing care. Some perceived medication to be offered as a 'quick fix' and feared potential drug interactions. CONCLUSION: Prior experiences can lead patients with RA and comorbid anxiety and depression to feel they lack candidacy for care. Provision of equal priority to mental and physical health problems by GPs and improved continuity of care could help disclosure of mood concerns. Facilitation of access to psychological therapies could improve outcomes for both mental and physical health problems

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

Intravenous iron preparations transiently generate non-transferrin-bound iron from two proposed pathways

Intravenous iron-carbohydrate complex preparations (IVIPs) are non-interchangeable pro-drugs: their pharmacokinetics (PK) varies determined by semi-crystalline iron core and carbohydrate shell structures, influences pharmacodynamics (PD) and thus efficacy and safety. Examining PK/PD relationships of 3 IVIPs we identify a two-pathway model of transient NTBI generation following single dose administration. 28 hypoferremic non-anemic patients randomized to 200mg iron as ferric carboxymaltose (Fe-carboxymaltose), iron sucrose (Fe-sucrose), iron isomaltoside 1000 (Fe-isomaltoside-1000), n=8/arm, or placebo, n=4, on a 2-week PK/PD study, had samples analysed for total serum iron, IVIP-iron, transferrin-bound iron (TBI) by HPLC-ICP-MS, transferrin saturation (TSAT), serum ferritin (s-Ferritin) by standard methods, non-TBI (NTBI) and hepcidin as published before. IVIP-dependent increases in these parameters returned to baseline in 48-150h, except for s-Ferritin and TSAT. NTBI was low with Fe-isomaltoside-1000 (0.13µM at 8h), rapidly increased with Fe-sucrose (0.8µM at 2h, 1.25µM at 4h), and delayed for Fe-carboxymaltose (0.57µM at 24h). NTBI AUCs were 7-fold greater for Fe-carboxymaltose and Fe-sucrose than for Fe-isomaltoside-1000. Hepcidin peak time varied, but not AUC or mean levels. s-Ferritin levels and AUC were highest for Fe-carboxymaltose and greater than placebo for all IVIPs. We propose 2 mechanisms for the observed NTBI kinetics: rapid and delayed NTBI appearance consistent with direct (circulating IVIP-to-plasma) and indirect (IVIP-to-macrophage-to-plasma) iron release based on IVIP plasma half-life and s-Ferritin dynamics. IVIPs generate different, broadly stability- and PK-dependent, NTBI and s-Ferritin signatures, which may influence iron bioavailability, efficacy and safety. Longer-term studies should link NTBI exposure to subsequent safety and efficacy parameters and potential clinical consequences

Searching for a prodrome for rheumatoid arthritis in the primary care record: a case-control study in the Clinical Practice Research Datalink

Background: Rheumatoid arthritis (RA) has articular and non-articular manifestations. Early, intensive treatment has substantial benefit for both. This requires patients be identified as soon as symptoms develop. Objectives: To determine whether selected signs and symptoms can be identified in the primary care records of patients prior to a formal diagnosis of RA being made and, if so, how early they can be identified. Methods: A case-control study was constructed within the UK Clinical Practice Research Datalink (CPRD). 3577 individuals with 'definite' RA, were matched to 14287 individuals without inflammatory arthritis. An index date was established (i.e. date general practitioner (GP) first appeared to suspect RA). Rates of consultation and consultations for suspected early RA symptoms were compared in cases and controls in the two years prior to the index date using conditional logistic regression, adjusted for number of consultations. Results: The mean (standard deviation) age of participants was 58.8 (14.5) years and 66.8% were female. Rates of any consultation were significantly higher in RA cases than in controls for at least two years prior to the index date. Cases were more likely to have a pre-diagnosis coded consultation for joint, and particularly hand symptoms (aOR 11.44 (9.60, 13.63)), morning stiffness (8.10 (3.54, 18.5)), carpal tunnel syndrome (4.57 (3.54, 5.88)) and other non-articular features. Conclusions: In patients who develop RA, GP consultation rates are higher for at least two years prior to the first recorded suspicion of RA. This study highlights symptoms that should raise a GP’s index of suspicion for RA

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

Total synthesis and biological evaluation of the tetramic acid based natural product harzianic acid and its stereoisomers

Financial support for this project was provided by Cancer Research UK (Grant No. C21383/A6950)The bioactive natural product harzianic acid was prepared for the first time in just six steps (longest linear sequence) with an overall yield of 22%. The identification of conditions to telescope amide bond formation and a Lacey-Dieckmann reaction into one pot proved important. The three stereoisomers of harzianic acid were also prepared, providing material for comparison of their biological activity. While all of the isomers promoted root growth, improved antifungal activity was unexpectedly associated with isomers in the enantiomeric series opposite that of harzianic acid.Publisher PDFPeer reviewe