Presentation of SLE in UK primary care using the Clinical Practice Research Datalink.

OBJECTIVES: To describe the presenting symptoms of SLE in primary care using the Clinical Practice Research Database (CPRD) and to calculate the time from symptom presentation to SLE diagnosis. METHODS: Incident cases of SLE were identified from the CPRD between 2000 and 2012. Presenting symptoms were identified from the medical records of cases in the 5 years before diagnosis and grouped using the British Isles Lupus Activity Group (BILAG) symptom domains. The time from the accumulation of one, two and three BILAG domains to SLE diagnosis was investigated, stratified by age at diagnosis (<30, 30-49 and ≥50 years). RESULTS: We identified 1426 incident cases (170 males and 1256 females) of SLE. The most frequently recorded symptoms and signs prior to diagnosis were musculoskeletal, mucocutaneous and neurological. The median time from first musculoskeletal symptom to SLE diagnosis was 26.4 months (IQR 9.3-43.6). There was a significant difference in the time to diagnosis (log rank p<0.01) when stratified by age and disease severity at baseline, with younger patients <30 years and those with severe disease having the shortest times and patients aged ≥50 years and those with mild disease having the longest (6.4 years (IQR 5.8-6.8)). CONCLUSIONS: The time from symptom onset to SLE diagnosis is long, especially in older patients. SLE should be considered in patients presenting with flaring or chronic musculoskeletal, mucocutaneous and neurological symptoms.

Safety of Fluticasone Propionate Prescribed for Asthma During Pregnancy: A UK Population-Based Cohort Study.

BACKGROUND: Asthma is commonly treated during pregnancy, yet data on the safety of asthma medicines used during pregnancy are sparse. OBJECTIVE: The objective of this study was to evaluate the safety of the inhaled corticosteroid (ICS) fluticasone propionate (FP), alone and in fixed-dose combination with salmeterol (FSC) in terms of the risk of all major congenital malformations (MCMs), compared with all other non-FP ICS. METHODS: Women with asthma who had a pregnancy between January 1, 2000, and December 31, 2010, were identified in the United Kingdom's Clinical Practice Research Datalink. Exposure to asthma medicines during the first trimester of pregnancy was based on issued prescriptions. The mothers' and infants' medical records were linked where possible, and pregnancy outcomes with an MCM diagnosed by age 1 year were identified based on medical codes in the mother's and infant's medical records, including those MCMs prenatally diagnosed that ended in an induced pregnancy termination. The absolute and relative risks of an MCM after different ICS exposures, stratified by the asthma treatment intensity level, were calculated. RESULTS: A total of 14,654 mother-infant pairs were identified, of which 6,174 received an ICS prescription during the first trimester, in addition to 13 first trimester ICS exposed pregnancies that ended in an induced termination after a prenatal MCM diagnosis. In total, 5,362 pregnancies were eligible for the primary analysis at age 1 year. The absolute risk of an MCM after any first trimester FP exposure was 2.4% (CI95 0.8-4.1) and 2.7% (CI95 1.8-3.6) for the "moderate" and "considerable/severe" asthma treatment intensity levels, respectively. The adjusted odds ratios when compared with non-FP ICS were 1.1 (CI95 0.5-2.3) and 1.2 (CI95 0.7-2.0) for the "moderate" and "considerable/severe" intensity levels; risks for any FP and for FSC did not differ substantially. CONCLUSION: No increase in the overall risk of MCMs was identified after first trimester FP exposure compared with non-FP ICS.

Estimating the diagnostic accuracy of rheumatoid factor in UK primary care: a study using the Clinical Practice Research Datalink.

OBJECTIVE: To investigate the diagnostic accuracy of RF as a test for RA in primary care and its impact on referral times using the Clinical Practice Research Datalink. METHODS: We identified all patients with a first RF test recorded in the Clinical Practice Research Datalink between 1 January 2000 and 31 December 2008 and those diagnosed with RA within 2 years of testing. We calculated likelihood ratios (LRs), sensitivity, specificity and predictive values of RF for a diagnosis of RA. We compared time to hospital referral in those testing positive and negative using Kaplan-Meier failure curves and log-rank tests. RESULTS: Of 62 436 first RF tests, 4679 (7.5%) were positive. There were 1753 incident cases of RA, of which 57.8% were seropositive. The positive LR for RF was 9.5 (95% CI 9.0, 10.0) and the negative LR was 0.5 (95% CI 0.4, 0.5). Sensitivity and specificity were 57.8% (95% CI 55.4%, 60.1%) and 93.9% (95% CI 93.7%, 94.1%) and the positive predictive value and negative predictive value were 21.4% (95% CI 20.3%, 22.6%) and 98.7% (95% CI 98.6%, 98.8%), respectively. Median time to first hospital contact after the first RF test in those with seropositive vs seronegative results was 54 days (95% CI 49, 58) vs 150 (95% CI 147, 152). CONCLUSION: Only 2.8% of patients undergoing RF testing were diagnosed with RA, suggesting that RF is used to screen patients with musculoskeletal symptoms rather than those with more specific features of RA. A positive RF test may be helpful in diagnosing RA in primary care but performs badly in excluding RA and may delay referral.

Missing laboratory test data in electronic general practice records: analysis of rheumatoid factor recording in the clinical practice research datalink.

PURPOSE: To investigate whether information from the literature could be used to identify periods of practice data in an electronic healthcare database during which rheumatoid factor (RF) test results are likely to be missing-not-at-random (MNAR). METHODS: RF tests recorded in the Clinical Practice Research Datalink (CPRD) were identified and defined as having a positive, negative or missing result. The proportion of positive test results was then calculated based on (i) complete-case analysis (ii) after restriction to tests from practice years with no missing test results and (iii) following multiple imputation of missing test results. The same three analyses were then carried out after excluding practice years with a proportion of positive tests incompatible with the missing completely at random (MCAR) assumption. RESULTS: We identified 127,969 RF test records, 30.4% of which did not have an associated test result. Among tests with results available, 19% were positive. Both multiple imputation of the 38,867 missing test results and restriction of the study population to the 491 practice years with complete data had little impact on the percentage of positive tests. Following exclusion of the 544 practice years in which data were likely to be MNAR the percentage of positive tests in all analyses decreased to ~7%. CONCLUSIONS: Recording of RF tests and RF test results in the CPRD is incomplete, with data likely to be MNAR in many practices. Exclusion of practice years with a high proportion of positive tests brought the distribution of positive tests in the study in line with the literature.

Serum soluble bone turnover biomarkers in psoriatic arthritis and psoriatic spondyloarthropathy.

Because psoriatic arthritis (PsA) is an inflammatory disease of joints, serum soluble biomarkers specific for chronic joint and bone inflammation may predict future disease severity and response to therapy, thereby informing stratified medicine approaches. The objectives of our systematic review were to determine whether serum soluble bone and cartilage turnover biomarkers are (1) associated with PsA or psoriatic spondyloarthropathy; and (2) associated with disease activity, disease severity, or clinical phenotype. Ten studies met eligibility criteria. Matrix metalloproteinase (MMP)-3, Dickkopf (DKK)-1, macrophage colony-stimulating factor (M-CSF), crosslinked telopeptide of collagen-1, and tumor necrosis factor-related apoptosis-inducing ligand were associated with PsA, with equivocal results for osteoprotegerin (OPG) and bone alkaline phosphatase (ALP). MMP-3, DKK-1, M-CSF, CPII:C2C (ratio of cartilage degradation vs byproduct formation), and possibly OPG were associated with PsA independently of psoriasis. C1-2C (a neoepitope released when type 2 cartilage is degraded by collagenases) was associated with both tender and swollen joint counts, and bone morphogenetic protein-4 with patient global assessment of disease, pain score, and the Bath Ankylosing Spondylitis Disease Activity Index. Bone ALP was associated with disease activity. M-CSF and receptor activator of nuclear factor-κB ligand were associated with several plain radiographic features. No studies have investigated biomarker associations specifically with axial PsA.

Patients' experiences and satisfaction with out-of-hours GP home visiting provided by a GP cooperative.

BACKGROUND: Within the UK, patients place a fairly high value on the out-of-hours GP home visiting service. Although satisfaction with the range of out-of-hours services has been found to be high, little is known about patients' specific experiences of the home visiting services. OBJECTIVE: To investigate the satisfaction with, and experiences of, patients receiving a GP out-of-hours (OOH) home visit from a GP cooperative. METHODS: A postal questionnaire study sent to all patients receiving a home visit from a single cooperative. The questionnaire asked patients a range of questions about their experiences of the home visiting service that they received and also contained a validated satisfaction measure. RESULTS: The OOH home visiting services largely provide care for an older population, most of whom consider that they are either too ill to travel or have limited mobility. The majority (43%) of home visits are made during the daytime at weekends, with just 25% of visits made during the night-time. If the home visit was not available, 67% of patients stated that they would have phoned for an ambulance or gone directly to hospital. The majority of patients (87%) were satisfied with the overall home visiting service that they received; however, 32% of patients were dissatisfied with the time it took for them to see a doctor or a nurse. CONCLUSIONS: Although the OOH services have received considerable criticism over the past 5 years, this study reveals that patients remain largely satisfied with the service and would have called 999 or gone directly to hospital if there had been no service.

Incidence of clinically diagnosed systemic lupus erythematosus 1992-1998 using the UK General Practice Research Database.

PURPOSE: To determine the age- and sex-specific incidence rates of systemic lupus erythematosus (SLE) in the population of the General Practice Research Database (GPRD) between 1.1.1992 and 31.12.1998. METHODS: We searched the GPRD for incident cases of clinically diagnosed SLE with supporting evidence of diagnosis in their medical record. Cases must have had at least 3 years of data in their record prior to date of first diagnosis. We calculated the annual and age- and sex-specific incidence rates of SLE. RESULTS: We identified 390 incident cases of SLE yielding an incidence rate (IR) of 3.02/100 000/year (CI(95) 2.72, 3.32). There were 41 males (IR 0.65/100 000/year (CI(95) 0.45, 0.85)) and 349 females (IR 5.30/100 000/year (CI(95) 4.75, 5.86)). The median age at diagnosis for males and females was 54 and 46 years, respectively, and the peak incidence rates were amongst women aged 30-69 years. The incidence rate ratio for females to males was 8.15 (CI(95) 5.9, 11.6). CONCLUSIONS: This is the first UK-wide study of the incidence of SLE. The results of this study are consistent with previous smaller studies conducted in Nottingham and Birmingham. Although recording of symptoms of SLE is not complete in the GPRD, we conclude that incident cases can be successfully identified because generally there is supporting evidence of diagnosis in medical record.

Ischemic stroke in young women: a nested case-control study using the UK General Practice Research Database.

BACKGROUND AND PURPOSE: Estimates of the incidence of ischemic stroke in young women vary widely from 0.9 to 8.9 per 100,000 per year. This study was conducted to determine the incidence and risk factors for ischemic stroke in young women in the UK. METHODS: Women aged 15 to 49 with a first diagnosis and supporting evidence of ischemic stroke between January 1, 1992, and December 31, 1998, were identified from the UK General Practice Research Database. Age-specific incidence rates were calculated and a nested case-control study was conducted with up to 6 controls randomly selected and matched to each case by year of birth and general practice. Crude and adjusted odds ratios (ORs) were calculated using conditional logistic regression. RESULTS: The incidence of ischemic stroke was 3.56/100 000 per year. Factors associated with an increased risk were heart disease (OR, 10.5), heavy alcohol consumption (OR, 8.5), previous venous thromboembolism (OR, 6.2), treated diabetes mellitus (OR, 4.7), hypertension (OR, 4.6), migraine (OR, 2.3), and use of combined oral contraceptives (OR, 2.3). Light alcohol consumption was found to be protective (OR, 0.17). CONCLUSIONS: The crude incidence rate was lower than previously reported for the USA and Europe but higher than that reported for the UK Oxford Region. This could be because of an under-representation of mild cases or because of a true lower incidence in the UK compared with the USA and the rest of Europe. The results of the case-control study are consistent with previous studies of ischemic stroke in young women.