Scientific
publications

BACKGROUND: There are conflicting reports in the literature of the mortality risk among patients with psoriatic arthritis (PsA). The objective of this study was to examine the risk of mortality in patients with PsA compared with matched controls, patients with psoriasis and those with rheumatoid arthritis (RA). METHODS: A longitudinal cohort study was performed in a large UK medical record database, The Health Improvement Network, among patients with PsA, rheumatoid arthritis (RA) or psoriasis with data from 1994 to 2010. Unexposed controls were matched on practice and start date within the practice for each patient with PsA. Cox proportional hazards models were used to calculate the relative hazards for death. RESULTS: Patients with PsA (N=8706), RA (N=41 752), psoriasis (N=138 424) and unexposed controls (N=82 258) were identified; 1 442 357 person-years were observed during which 21 825 deaths occurred. Compared with population controls, patients with PsA did not have an increased risk of mortality after adjusting for age and sex (disease-modifying antirheumatic drug (DMARD) users: HR 0.94, 95% CI 0.80 to 1.10; DMARD non-users: HR 1.06, 95% CI 0.94 to 1.19) whereas patients with RA had increased mortality (DMARD users: HR 1.59, 95% CI 1.52 to 1.66; DMARD non-users: HR 1.54, 95% CI 1.47 to 1.60). Patients with psoriasis who had not been prescribed a DMARD had a small increased risk of mortality (HR 1.08, 95% CI 1.04 to 1.12) while those who had been prescribed a DMARD, indicating severe psoriasis, were at increased risk (HR 1.75, 95% CI 1.56 to 1.95). CONCLUSIONS: Patients with RA and psoriasis have increased mortality compared with the general population but patients with PsA do not have a significantly increased risk of mortality.

BACKGROUND: Involvement of large arteries is well-documented in giant-cell arteritis (GCA), but the risk for cardiovascular events is not well-understood. OBJECTIVE: To evaluate the risks for incident myocardial infarction (MI), cerebrovascular accident (CVA), and peripheral vascular disease (PVD) in individuals with incident GCA in a general population context. DESIGN: Observational cohort study. SETTING: U.K. primary care database. PATIENTS: 3408 patients with incident GCA and 17 027 age- and sex-matched reference participants without baseline cardiovascular disease (MI, CVA, or PVD). MEASUREMENTS: Diagnoses of GCA, outcomes, and cardiovascular risk factors were identified from electronic medical records. One combined and 3 separate cohort analyses were conducted for the outcomes of MI, CVA, and PVD. The association of GCA with study outcomes is expressed with hazard ratios (HRs) with 95% CIs after adjustment for potential cardiovascular risk factors. RESULTS: Among 3408 patients with GCA (73% female; mean age, 73 years), the incidence rates of MI, CVA, and PVD were 10.0, 8.0, and 4.2 events per 1000 person-years, respectively, versus 4.9, 6.3, and 2.0 events per 1000 person-years, respectively, among reference participants. The HRs were 1.70 (95% CI, 1.51 to 1.91) for the combined outcome, 2.06 (CI, 1.72 to 2.46) for MI, 1.28 (CI, 1.06 to 1.54) for CVA, and 2.13 (CI, 1.61 to 2.81) for PVD. The HRs were more pronounced in the first month after GCA diagnosis (combined HR, 4.92 [CI, 2.59 to 9.34]; HR for MI, 11.89 [CI, 2.40 to 59.00]; HR for CVA, 3.93 [CI, 1.76 to 8.79]; HR for PVD, 3.86 [CI, 0.78 to 19.17]). LIMITATION: Information on temporal arterial biopsies was not available, and there was a substantial amount of missing data on cardiovascular risk factors. CONCLUSION: Giant-cell arteritis is associated with increased risks for MI, CVA, and PVD. PRIMARY FUNDING SOURCE: National Institute of Arthritis and Musculoskeletal and Skin Diseases.

BACKGROUND: The benefit-risk profile of low-dose aspirin in primary prevention of cardiovascular disease is unclear. We sought to quantify upper gastrointestinal bleeding (UGIB) risk associated with low-dose aspirin in secondary versus primary prevention patients. METHODS AND RESULTS: We performed a population-based nested case-control study using The Health Improvement Network (THIN) Database between 2000 and 2007. We identified 2049 cases of UGIB and 20,000 controls, frequency-matched to the cases on age, sex, and calendar year, who were subdivided into primary (without previous cardiovascular disease) and secondary (with previous cardiovascular disease) prevention populations. We estimated the relative risk of UGIB associated with the use of low-dose aspirin by multivariate logistic regression. The UGIB risk in patients taking low-dose aspirin relative to nonusers was significantly higher in the primary (adjusted relative risk, 1.90; 95% confidence interval, 1.59-2.26) than in the secondary (relative risk, 1.40; 95% confidence interval, 1.14-1.72; P value for the difference=0.0014) prevention cohort. However, as the baseline risk of UGIB was lower in the primary than in the secondary prevention cohort, numbers needed to harm per 1 year of low-dose aspirin use were 601 and 391 for primary and secondary prevention, respectively. CONCLUSIONS: The relative risk of UGIB in patients taking low-dose aspirin is higher when used for primary than for secondary cardiovascular disease prevention, but this difference is more than compensated by the lower baseline risk in the primary prevention population. Such estimates are important for an assessment of the net clinical benefit in primary prevention.

AIMS: To provide evidence on the comparative effectiveness of oral diabetes drug combinations. METHODS: We performed a retrospective, observational cohort study of glycosylated hemoglobin change in outpatients newly exposed to dual- or triple-drug oral diabetes treatment. RESULTS: Adjusted response to a second drug added to metformin ranged from 0.85 to 1.21% glycosylated hemoglobin decline. Response to a third drug was smaller (0.53-0.91%). Higher baseline glycosylated hemoglobin was associated with larger response; sulfonylurea effectiveness declined over time; and thiazolidinediones were more effective in obese patients and women. CONCLUSION: Observational data provide results qualitatively consistent with the limited available randomized data on diabetes drug effectiveness, and extend these findings into common clinical scenarios where randomized data are unavailable. Sex and BMI influence the comparative effectiveness of diabetes drug combinations.

BACKGROUND: The potential to use data on family history of premature disease to assess disease risk is increasingly recognised, particularly in scoring risk for coronary heart disease (CHD). However the quality of family health information in primary care records is unclear. AIM: To assess the availability and quality of family history of CHD documented in electronic primary care records. DESIGN: Cross-sectional study. SETTING: 537 UK family practices contributing to The Health Improvement Network database. METHOD: Data were obtained from patients aged 20 years or more, registered with their current practice between 1(st) January 1998 and 31(st) December 2008, for at least one year. The availability and quality of recorded CHD family history was assessed using multilevel logistic and ordinal logistic regression respectively. RESULTS: In a cross-section of 1,504,535 patients, 19% had a positive or negative family history of CHD recorded. Multilevel logistic regression showed patients aged 50-59 had higher odds of having their family history recorded compared to those aged 20-29 (OR:1.23 (1.21 to 1.25)), however most deprived patients had lower odds compared to those least deprived (OR: 0.86 (0.85 to 0.88)). Of the 140,058 patients with a positive family history recorded (9% of total cohort), age of onset was available in 45%; with data specifying both age of onset and relative affected available in only 11% of records. Multilevel ordinal logistic regression confirmed no statistical association between the quality of family history recording and age, gender, deprivation and year of registration. CONCLUSION: Family history of CHD is documented in a small proportion of primary care records; and where positive family history is documented the details are insufficient to assess familial risk or populate cardiovascular risk assessment tools. Data capture needs to be improved particularly for more disadvantaged patients who may be most likely to benefit from CHD risk assessment.

BACKGROUND: There is increasing emphasis on primary care services for individuals with severe mental illnesses (SMI), including schizophrenia, bipolar disorder, and other non-organic psychotic disorders. However we lack information on how many people receive these different diagnoses in primary care. Primary care databases offer an opportunity to explore the recording of new SMI diagnoses in representative general practices. METHODS: We used data from The UK Health Improvement Network (THIN) primary care database including longitudinal patient records for individuals aged over 16 years from 437 general practices. We determined the annual GP recorded rate of first diagnosis of SMI by age, gender, social deprivation and urbanicity between 2000 and 2010. RESULTS: We identified 10,520 individuals with a first record of schizophrenia, bipolar disorder or other non-organic psychosis among 4,164,794 patients. This corresponded to a rate of first diagnosis of 46.4 per 100,000 person years at risk (PYAR) (95% CI 45.4 to 47.4) in the 16-65 age group. The rate of first record of schizophrenia was 9.2 per 100,000 PYAR (95% CI 8.7 to 9.6) in this age group, bipolar disorder was 15.0 per 100,000 PYAR (95% CI 14.4 to 15.5) and other non-organic psychotic disorder was 22.3 per 100,000 PYAR (95% CI 21.6 to 23.0). CONCLUSIONS: The rates of GP recorded SMI in primary care records were broadly comparable to incidence rates from previous epidemiological studies of SMI and show similar patterns by socio-demographic characteristics. However there were some differences by specific diagnoses. GPs may be recording rates that are higher than those used to commission services.

BACKGROUND: In clinical trials, the use of inhaled corticosteroids is associated with an increased risk of pneumonia in people with COPD, but whether the same is true for people with asthma is not known. METHODS: With the use of primary care data from The Health Improvement Network, we identified people with asthma, and from this cohort, we identified patients with pneumonia or lower respiratory tract infection and age- and sex-matched control subjects. Conditional logistic regression was used to determine the association between the dose and type of inhaled corticosteroid and the risk of pneumonia or lower respiratory tract infection. RESULTS: A dose-response relationship was found between the strength of inhaled corticosteroid dose and risk of pneumonia or lower respiratory tract infection (P < .001 for trend) such that after adjusting for confounders, people receiving the highest strength of inhaled corticosteroid (≥ 1,000 μg) had a 2.04 (95% CI, 1.59-2.64) increased risk of pneumonia or lower respiratory tract infection compared with those with asthma who did not have a prescription for inhaled corticosteroids within the previous 90 days. CONCLUSIONS: People with asthma receiving inhaled corticosteroids are at an increased risk of pneumonia or lower respiratory infection, with those receiving higher doses being at greater risk. Pneumonia should be considered as a possible side effect of inhaled corticosteroids, and the lowest possible dose of inhaled corticosteroids should be used in the management of asthma.

BACKGROUND: Bereavement is a period of increased risk of cardiovascular death. There is limited understanding of the potential contribution of quality of cardiovascular disease management to this increased risk. METHODS AND RESULTS: In a UK primary-care database, 12 722 older individuals with preexisting cardiovascular disease (coronary heart disease, hypertension, diabetes mellitus, stroke) and a partner bereavement were matched with a non-bereaved control group (n=33 911). We examined key routine annual process measures of care in the year before and after bereavement and cardiovascular medication prescribing (lipid-lowering, antiplatelet, renin-angiotensin system drugs). Odds ratios for change after bereavement compared with the change in non-bereaved matched controls are presented. In the bereaved, uptake of all annual measures was lower in the year before bereavement, with improvement in the year after, whereas in the controls, uptake was relatively stable. The odds ratio for change was 1.30 (95% confidence interval, 1.15-1.46) for cholesterol measurement and 1.40 (95% confidence interval, 1.22-1.61) for blood pressure measurement. For all medication, there was a transient fall in prescribing in the peri-bereavement period lasting until about 3 months after bereavement. The odds ratio for at least 80% prescription coverage in the 30 days after bereavement was 0.80 (95% confidence interval, 0.73-0.88) for lipid-lowering medication and 0.82 (95% confidence interval, 0.74-0.91) for antiplatelet medication compared with the change in non-bereaved individuals. CONCLUSIONS: Lower uptake of key cardiovascular care measures in the year before bereavement and reduced medication coverage after bereavement may contribute to increased cardiovascular risk. Clinicians need to ensure that quality of cardiovascular care is maintained in the pre- and post-bereavement periods.

AIMS/HYPOTHESIS: The aim of this study was to determine the contemporary rate ratio of mortality and changes over time in individuals with vs without diabetes. METHODS: Annual age- and sex-adjusted mortality rates were compared for adults (>20 years) with and without diabetes in Ontario, Canada, and the UK from January 1996 to December 2009 using The Health Improvement Network (THIN) and Ontario databases. The total number of individuals evaluated increased from 8,757,772 in 1996 to 12,696,305 in 2009. RESULTS: The excess risk of mortality for individuals with diabetes in both cohorts was significantly lower during later vs earlier years of the follow-up period (1996-2009). In Ontario the diabetes mortality rate ratio decreased from 1.90 (95% CI 1.86, 1.94) in 1996 to 1.51 (1.48, 1.54) in 2009, and in THIN from 2.14 (1.97, 2.32) to 1.65 (1.57, 1.72), respectively. In Ontario and THIN, the mortality rate ratios among diabetic patients in 2009 were 1.67 (1.61, 1.72) and 1.81 (1.68, 1.94) for those aged 65-74 years and 1.11 (1.10, 1.13) and 1.19 (1.14, 1.24) for those aged over 74 years, respectively. Corresponding rate ratios in Ontario and THIN were 2.45 (2.36, 2.54) and 2.64 (2.39, 2.89) for individuals aged 45-64 years, and 4.89 (4.35, 5.45) and 5.18 (3.73, 6.69) for those aged 20-44 years. CONCLUSIONS/INTERPRETATION: The excess risk of mortality in individuals with vs without diabetes has decreased over time in both Canada and the UK. This may be in part due to earlier detection and higher prevalence of early diabetes, as well as to improvements in diabetes care.

OBJECTIVE: We investigated the circumstances of ezetimibe discontinuation as its prescribing had been discouraged in some publications. RESEARCH DESIGN AND METHODS: Adults on stable lipid-modifying therapy (LMT) including ezetimibe, who then had >8 weeks cessation in their prescribed ezetimibe regimen (2010-2011) were identified from THIN UK primary care database. Lipid values and parallel changes to other LMT were described overall and in a sub-group with a history of diabetes, cardiovascular disease or familial hypercholesterolaemia (high-risk group). RESULTS: Ezetimibe therapy stopped in 7087 patients after a mean of 38 months; 67.0% were in the high-risk group. No lipid readings were recorded for 16.1% of patients in the year before and 26.2% in the year after ezetimibe stopped; 11.0% and 12.4% in the high-risk group respectively. In the prior year, 60.2% patients with any lipid reading had a total cholesterol (T-cholesterol) <5 mmol/l and 59.2% had a T-cholesterol <5 mmol/l and LDL-cholesterol <3 mmol/l. In the high-risk group, 66.8% had a T-cholesterol <5 mmol/l, 38.9% had either a T-cholesterol <4 or a LDL-cholesterol <2 mmol/l and 29.4% had reached both targets. In both populations, 42% patients had 6 months' follow-up after ezetimibe stopped with no change to other LMT. An LMT change within 8 weeks (19%) was usually a new statin while 27% overall had a further ezetimibe prescription after 8-26 weeks. LIMITATIONS: Only absolute lipid values were included, as percentage change from baseline level may not be reliable. The study included a larger proportion of patients in Scotland relative to the UK population. CONCLUSIONS: Prescribed ezetimibe often stopped without either a recent lipid value or attainment of optimal, or sometimes minimum, lipid targets. Patients did not always receive parallel intensification of other LMT or a further ezetimibe prescription within 6 months.