General Practice Research Database Population Research Articles

CHANGING FACE OF MULTIPLE SCLEROSIS IN THE UNITED KINGDOM 1990–2010. AN INCIDENCE AND PREVALENCE STUDY

BackgroundOur knowledge of the impact of Multiple Sclerosis throughout the UK as a whole is often based on extrapolation from small regional studies. There have been few nationwide studies.MethodsWe sought...

Androgen deprivation therapy and the risk of colorectal cancer in patients with prostate cancer

Androgens are known to play an important protective role on colorectal carcinogenesis, and thus the objective of this study was to determine whether androgen deprivation therapy (ADT) is associated with an increased risk of incident colorectal cancer in patients with prostate cancer. We conducted a population-based cohort study within the UK General Practice Research Database population which included all patients newly diagnosed with prostate cancer between 1 January 1988 and 31 December 2008, followed until 31 December 2009. Time-dependent Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) of incident primary colorectal cancer associated with the use of ADT. Secondary analyses considered cumulative duration of use and specific ADTs. The cohort included a total of 21,503 patients, of whom 184 were diagnosed with colorectal cancer during a mean (SD) follow-up 4.0 (3.0) years (rate 2.4/1,000 person-years). Overall, use of ADT was not associated with an increased risk of colorectal cancer (HR 0.99, 95 % CI 0.73-1.35). Similarly, no association was observed in terms of duration use, although this secondary analysis may have been limited by statistical power. With respect to specific ADTs, bilateral orchiectomy was the only therapy associated with an increased risk of colorectal cancer (HR 2.50, 95 % CI 1.13-5.52). Overall, the use of ADT is not associated with an increased risk of incident colorectal cancer. The increased risk observed with bilateral orchiectomy may possibly be due to the prolonged androgen suppression of this therapy.

Androgen-Deprivation Therapy and the Risk of Stroke in Patients With Prostate Cancer

BackgroundSome evidence indicates that androgen-deprivation therapy (ADT) increases the risk of diabetes and cardiovascular disease. To date, few studies have investigated whether this therapy also increases the risk of cerebrovascular events. ObjectiveTo determine whether different types of ADT increase the risk of stroke/transient ischaemic attacks (TIAs) in patients with prostate cancer. Design, setting, and participantsWe conducted a population-based cohort study using a nested case-control analysis within the United Kingdom's General Practice Research Database population. The cohort included all patients at least 40 yr of age newly diagnosed with prostate cancer between January 1, 1988, and December 31, 2008, and followed until December 31, 2009. Cases consisted of those who experienced a first-ever stroke/TIA during follow-up. Up to 10 controls were matched to each case on age, year of cohort entry, and duration of follow-up. MeasurementsAdjusted rate ratios (RRs) of stroke/TIA associated with the use of different ADTs (gonadotropin-releasing hormone [GnRH] agonists, oral antiandrogens, combined androgen blockade, bilateral orchiectomy, and others) were estimated using conditional logistic regression. Results and limitationsThe cohort included 22 310 patients with prostate cancer, followed for a mean of 3.9 yr, where 938 patients experienced a first-ever stroke/TIA (rate: 10.7 per 1000/yr). Compared with nonusers of ADT, current users of GnRH agonists (adjusted RR: 1.18; 95% confidence interval [CI], 1.00–1.39), oral antiandrogens (adjusted RR: 1.47; 95% CI, 1.08–2.01), and those who underwent bilateral orchiectomy (adjusted RR: 1.77; 95% CI, 1.25–2.39) were at an increased risk of stroke/TIA. No statistically significant increased risks were observed for patients on combined androgen blockade and other ADTs, but the small numbers do not rule out a possible association. ConclusionsThe results of this large population-based study provide additional evidence that different forms of ADT may increase the risk of stroke/TIA.

The use of atypical antipsychotics and the risk of breast cancer

To determine whether atypical antipsychotics, when compared to typical antipsychotics, increase the risk of breast cancer. We conducted a retrospective cohort study using a nested case-control analysis within the United Kingdom General Practice Research Database population. We identified all female patients prescribed at least one antipsychotic (either typical or atypical), between 1 January 1988 and 31 December 2007, with follow-up until 31 December 2010. All incident cases of breast cancer were identified and matched up to 10 controls. Adjusted rate ratios (RR) of breast cancer associated with ever use of atypical antipsychotics was compared to ever use of typical antipsychotics. The cohort included 106,362 patients prescribed antipsychotics during the study period. During a mean follow-up of 5.3years, 1237 patients were diagnosed with breast cancer (overall rate: 2.7 per 1000/year). Compared to patients who only used typical antipsychotics, exclusive users of atypical antipsychotics were not an increased risk of breast cancer (RR: 0.81, 95% CI: 0.63, 1.05). These results remained consistent after considering specific atypical antipsychotics known to significantly increase prolactin levels such as risperidone (RR: 0.86, 95% CI: 0.60, 1.25). Furthermore, no dose-response was observed in terms of cumulative duration of use and cumulative dose in olanzapine equivalents. The results of this study should provide reassurance that compared to typical antipsychotics, atypical antipsychotics do not increase the risk of breast cancer.

Reanalysis of two studies with contrasting results on the association between statin use and fracture risk: the General Practice Research Database

Two recent case-control studies by Meier et al. and van Staa et al. used the UK General Practice Research Database (GPRD) to examine the association between the use of statins and the risk of fractures, with different results. The objective of the present study was to examine methodological explanations for the discrepant results. We created two datasets, which mimicked the previous study designs: a 'selected population' (SP) case-control dataset, with fracture cases matched to controls nested within a selected cohort (Meier et al.), and an 'entire population' (EP) case-control dataset, with both cases and controls sampled from the total GPRD population (van Staa et al.). Cases and controls were matched by gender, age (year of birth or 5 year age bands), and general practice. The study included 131 855 fracture cases. The crude odds ratio (OR) for hip fracture in statin users was 0.37 (95% CI 0.27-0.52) in the SP and 0.54 (95% CI 0.39-0.74) in the EP dataset. This difference was reduced when matching by year of birth, rather than by 5 year age bands: crude ORs were 0.58 (95% CI 0.43-0.79) and 0.61 (95% CI 0.44-0.88), respectively. In the SP dataset, 37% of the cases could be matched by year of birth, while this was achieved for 99% in the 'EP' dataset. The exposure time-window, the selection of confounders, and exclusion of high-risk patients also influenced results. Residual confounding by a matching variable and different definitions of the exposure time window explained differences in results. In case-control studies of drug use and fracture risk, broad matching criteria for age should be avoided and the selection of the time-window for exposure should be carefully considered.

Prevalence and Treatment of Psoriasis in the United Kingdom

To measure the prevalence and treatment of psoriasis in the United Kingdom. Cross-sectional study to determine prevalence and cohort study to determine treatment patterns. Outpatient practices of general practitioners. We included in the analysis all patients who were registered with a general practitioner in the General Practice Research Database from 1987 to 2002. The prevalence and treatment of psoriasis. We identified 114 521 patients with psoriasis of a total population of 7 533 475 patients, yielding a prevalence of 1.5%. The prevalence of psoriasis increases more rapidly in young female patients compared with young male patients and declines significantly in patients 70 years and older, regardless of sex. Overall, 91.8% of patients with a diagnosis of psoriasis received a prescription for psoriasis treatment on or after the date of their first diagnostic code of psoriasis in the General Practice Research Database. Most of the patients (55.2%) received only 1 or 2 prescriptions for psoriasis in the first year after psoriasis was documented in the General Practice Research Database. The epidemiology of psoriasis in the General Practice Research Database population is similar to that of other epidemiologic studies of psoriasis performed in the United Kingdom, the United States, and other Western countries. Psoriasis carries a substantial burden given its high prevalence and its associated need for prescription therapy. Additional studies are necessary to determine why the prevalence of psoriasis increases more rapidly in female patients and to determine why the prevalence decreases in patients 70 years and older.

Incidence, prevalence and management of lower urinary tract symptoms in men in the UK

To describe the incidence, prevalence and management of lower urinary tract symptoms (LUTS), suggestive of benign prostatic hyperplasia, reported in UK general practice. All clinical information relating to LUTS and its treatment was assessed for men aged > or = 45 years and registered on the UK General Practice Research Database (GPRD) at some time between 1992 and 2001. Incidence and prevalence were derived from the GPRD population. Secular trends in the management of LUTS were examined from prescribing rates and the intervals between first symptoms, first treatment and surgery or catheterization. The incidence of reported LUTS showed a strong linear increase with age. The prevalence increased from 3.5% for men aged 45-49 years to > 30% for men aged > 85 years. Between 1992 and 2000 there was a five-fold increase in the proportion of time with LUTS when men were receiving medical treatment. This was accompanied by a progressive decrease in the intervals between first symptoms and first drug treatment, and a significant increase in the intervals from first symptoms or first treatment to surgery or catheterization. Treated men received surgery or catheterization significantly later than those receiving no drug treatment. There has been a significant increase in the use of medical therapy for LUTS over the last decade. The accompanying postponement of surgery/catheterization is likely to be a result, at least in part, of successful earlier medical treatment and the treatment of a greater proportion of symptomatic men.

Use of oral corticosteroids in the United Kingdom.

Administration of oral corticosteroids is associated with the development of osteoporosis and an increased risk of fractures. However, the size of the treated sub-population who would benefit from preventive therapy remains uncertain. The objective of this study was to investigate the usage pattern of oral corticosteroids in a large sample representative of the general population in England and Wales. Information was obtained from the General Practice Research Database (GPRD) which contains medical records of general practitioners. Oral corticosteroid users were patients aged 18 years or older who received one or more prescriptions for oral corticosteroids. Over 1.6 million oral corticosteroid prescriptions were issued to the cohort of 244 235 oral corticosteroid users. At any point in time, oral corticosteroids were being used by 0.9% of the total adult GPRD population. The highest use (2.5%) was by people between 70 and 79 years of age. Respiratory disease was the most frequently recorded indication for oral corticosteroid treatment (40%). Patients with arthropathies were most likely to use long-term, continuous treatment, and patients with chronic obstructive pulmonary disease least likely (19.3% and 6.1%, respectively, used oral corticosteroids for more than 2 years). The overall use of bone-active medication (oestrogens, bisphosphonates, vitamin D, and calcitonin) during oral corticosteroid treatment was low (between 4.0% and 5.5%). The current population in the UK at risk of developing corticosteroid-induced fractures might be as large as 350 000. Identification of these patients will be important for implementing preventive strategies in a cost-effective manner.