Katrina Wilcox Hagberg

The incidence of eating disorders in the UK in 2000–2009: findings from the General Practice Research Database

Objectives Few studies have investigated the incidence of eating disorders (EDs). Important questions about changes in the incidence of diagnosed disorders in recent years, disorder and gender-specific onset and case detection remain unanswered. Understanding changes in incidence is important for public health, clinical practice and service provision. The aim of this study was to estimate the annual (age-specific, gender-specific and subtype-specific) incidence of diagnosed ED: anorexia nervosa (AN), bulimia nervosa (BN) and eating disorder not otherwise specified (EDNOS) in primary care over a 10-year period in the UK (2000–2009); to examine the changes within the study period; and to describe peak age at diagnosis. Design Register-based study. Setting Primary care. Data were obtained from a primary care register, the General Practice Research Database, which contains anonymised records representing about 5% of the UK population. Participants All patients with a first-time diagnosis of AN, BN and EDNOS were identified. Primary outcome Annual crude and age-standardised incidence rates were calculated. Results A total of 9072 patients with a first-time diagnosis of an ED were identified. The age-standardised annual incidence rate of all diagnosed ED for ages 10–49 increased from 32.3 (95% CI 31.7 to 32.9) to 37.2 (95% CI 36.6 to 37.9) per 100 000 between 2000 and 2009. The incidence of AN and BN was stable; however, the incidence of EDNOS increased. The incidence of the diagnosed ED was highest for girls aged 15–19 and for boys aged 10–14. Conclusions The age-standardised incidence of ED increased in primary care between 2000 and 2009. New diagnoses of EDNOS increased, and EDNOS is the most common ED in primary care.

Postmarketing study of ORTHO EVRA and levonorgestrel oral contraceptives containing hormonal contraceptives with 30 mcg of ethinyl estradiol in relation to nonfatal venous thromboembolism

BACKGROUND Concern has been raised that the risk of venous thromboembolism (VTE) in users of the ORTHO EVRA patch is higher compared to users of oral contraceptives (OCs). STUDY DESIGN We identified idiopathic cases of VTE and controls, matched on age and index date, from among women in the United States PharMetrics/IMS and MarketScan databases who were current users of the patch or levonorgestrel-containing OCs with 30 mcg of ethinyl estradiol. We calculated odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS The ORs (95% CI) for VTE in users of the patch compared to levonorgestrel-containing OCs were 2.0 (0.9-4.1) and 1.3 (0.8-2.1) in the PharMetrics and MarketScan databases, respectively. ORs (95% CI) restricted to women aged 39 years or younger were 1.4 (0.6-3.0) and 1.2 (0.7-2.0), respectively. CONCLUSION These results provide evidence that the risk of idiopathic VTE in users of the patch is not materially different than that of users of levonorgestrel-containing OCs in women aged 39 years or younger. We cannot rule out some increase in the risk in women aged 40 years or older.

Postmenopausal estrogen-containing hormone therapy and the risk of breast cancer.

OBJECTIVE: To investigate the relation of various estrogen-containing hormone therapies to the risk of breast cancer, emphasizing the use of the combination of estrogen and testosterone. METHODS: Using information from a large U.S.–based claims database, we conducted a case–control study in women aged 50 to 64 years who had a first-time diagnosis of breast cancer to estimate the effect in users of conjugated estrogen alone, conjugated estrogen plus progestin, esterified estrogen with methyltestosterone, or esterified estrogen with methyltestosterone plus progestin, compared with nonusers. Four controls were matched to each case on year of birth and index date. Odds ratios (ORs) were calculated using conditional logistic regression. RESULTS: We identified 4,515 cases and 18,058 matched controls. The OR for users of estrogen alone compared with the nonusers was 0.96 (95% confidence interval [CI] 0.88–1.06; 667 cases and 2,900 controls); for users of conjugated estrogen plus progestin, it was 1.44 (95% CI 1.31–1.58; 712 cases and 2,087 controls); and for users of esterified estrogen with methyltestosterone and esterified estrogen with methyltestosterone plus progestin, the ORs were 1.08 (95% CI 0.86–1.36; 98 cases and 380 controls) and 1.69 (95% CI 1.03–2.79; 22 cases and 55 controls), respectively. There was an increased risk among conjugated estrogen plus progestin users of 48 months or more (OR 3.10, 95% CI 2.38– 4.04; 111 cases and 149 controls). CONCLUSION: There is no materially increased risk of breast cancer in users of estrogen alone or esterified estrogen with methyltestosterone compared with nonusers. There is an increased risk among those using conjugated estrogen plus progestin. In particular, the risk of breast cancer in women who used conjugated estrogen plus progestin for 4 or more years is approximately three times higher than in women who are not exposed to hormone therapy, so that the background incidence rate for women aged 50 to 64 years, which is around 3 per 1,000, would be increased to approximately 9 per 1,000 in women aged 50 to 64 years who have taken conjugated estrogen plus progestin for 48 months or more. LEVEL OF EVIDENCE: II

Statin Use and Risk of Primary Liver Cancer in the Clinical Practice Research Datalink

BACKGROUND Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are widely prescribed to reduce cholesterol levels. Studies have suggested that statins are associated with reduced risk of liver cancer, but much of the evidence is from regions of the world with high liver cancer incidence rates. The current study examined the statins-liver cancer relationship in a low-rate region and examined the effects of preexisting liver disease and diabetes on that association. METHODS A nested case-control study was conducted within the United Kingdoms Clinical Practice Research Datalink (CPRD). Persons diagnosed with primary liver cancer between 1988 and 2011 were matched to controls at a four-to-one ratio. Matches stratified on liver disease and on diabetes were also completed. Odds ratios (ORs) and 95% confidence intervals (CIs) for associations of statins with liver cancer were estimated using conditional logistic regression. RESULTS In total, 1195 persons with primary liver cancer were matched to 4640 control patients. Statin use was associated with a statistically significantly reduced risk of liver cancer (ORadj = 0.55, 95% CI = 0.45 to 0.69), especially among current users (ORadj = 0.53, 95% CI = 0.42 to 0.66). The reduced risk was statistically significant in the presence (ORadj = 0.32, 95% CI = 0.17 to 0.57) and absence of liver disease (ORadj = 0.65, 95% CI = 0.52 to 0.81) and in the presence (ORadj = 0.30, 95% CI = 0.21 to 0.42) and absence of diabetes (ORadj = 0.66, 95% CI = 0.51 to 0.85). CONCLUSIONS In the current study in a low-rate area, statin use was associated with a statistically significantly reduced risk of liver cancer overall. Risk was particularly reduced among persons with liver disease and persons with diabetes, suggesting that statin use may be especially beneficial in persons at elevated risk of liver cancer.

The origin and spread of a mumps epidemic: United Kingdom, 2003-2006.

Background: The United Kingdom (UK) underwent a massive epidemic of mumps from 2003 through 2006. The origin and spread was mapped in 350 general practices that used office computers to contribute comprehensive medical information on approximately 3 million patients to the General Practice Research Database (GPRD). Methods: The continuous 3-month cumulative incidence of mumps (2003–2006) was estimated by dividing the number of diagnosed cases of mumps each 3 months by the population at risk according to age, region, practice, and calendar time. The effect of the measles, mumps, and rubella (MMR) vaccine was estimated by comparing vaccine exposure of those diagnosed with mumps and those who were not. Results: There were 5683 cases of mumps recorded in the Database over the 4-year time period. As the Database represents about 5% of the UK population, we estimate that there were more than 100,000 cases of mumps diagnosed in the UK during these 4 years. The epidemic appears to have started in one practice in Wales in the first 6 months of 2003 and then spread slowly north and east, reaching a peak in 2005. Young adults aged 18–24 years were at the highest risk. There were 3 major MMR vaccination campaigns (1988–1989, 1997, and 2004–2005) that by 2006 provided more than 70% protection against mumps in children younger than 18 years of age. Protection was higher in those who had received 2 doses of the vaccine. Conclusion: A comprehensive program of medical information generated by selected general practitioners has provided a sound basis for the real-time recording of the origin, spread, and scope of an infectious disease.

Incidence of bone metastases in breast cancer patients in the United Kingdom: results of a multi-database linkage study using the general practice research database.

BACKGROUND Bone is a frequent site for metastases among women with breast cancer. We conducted a study using the General Practice Research Database (GPRD), with linkage to the National Cancer Registry (NCR) and Hospital Episode Statistics (HES), to estimate the incidence of bone metastases in women with breast cancer in the United Kingdom. METHODS We identified all women in the GPRD aged 20-99 with a first-time diagnosis of breast cancer between 2000 and 2006. To address potential underreporting, we developed and validated an algorithm to serve as a proxy for bone metastases. Bone metastases were defined as (1) a bone cancer diagnosis code on the same day or following breast cancer diagnosis date, or (2) another metastasis code plus codes consistent with bone metastases diagnosis or treatment using the algorithm. We sent questionnaires to a sample of general practitioners to validate these definitions. RESULTS We included 13,207 breast cancer patients (median age at diagnosis of 61 years) who contributed 70,885 person-years of follow-up. The majority of patients had stage 1 or 2 breast cancer (90.4%), and 2.6% had metastatic breast cancer at diagnosis. We identified 788 women (6.0%) with bone metastases after a median follow-up of 5.4 years. Questionnaire results validated the diagnosis of bone metastases in 88% of patients with a bone cancer code and for 70% identified with the algorithm. CONCLUSION This is the first time the GPRD has been linked to HES and NCR to study the epidemiology of bone metastases, adding important information on the burden of bone metastasis.

Anti-diabetic medications and risk of primary liver cancer in persons with type II diabetes

Background:Type II diabetes increases liver cancer risk but the risk may be mitigated by anti-diabetic medications. However, choice of medications is correlated with diabetes duration and severity, leading to confounding by indication.Methods:To address this association, we conducted a nested case–control study among persons with type II diabetes in the Clinical Practice Research Datalink. Cases had primary liver cancer and controls were matched on age, sex, practice, calendar time, and number of years in the database. Exposure was classified by type and combination of anti-diabetic prescribed and compared to non-use. Odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated using conditional logistic regression.Results:In 305 cases of liver cancer and 1151 controls, there was no association between liver cancer and anti-diabetic medication use compared to non-use (OR=0.74 (95% CI=0.45–1.20) for metformin-only, 1.10 (95% CI=0.66–1.84) for other oral hypoglycaemic (OH)-only, 0.89 (95% CI=0.58–1.37) for metformin+other OH, 1.11 (95% CI=0.60–2.05) for metformin+insulin, 0.81 (95% CI=0.23–2.85) for other OH+insulin, and 0.72 (95% CI=0.18–2.84) for insulin-only). Stratification by duration of diabetes did not alter the results.Conclusions:Use of any anti-diabetic medications in patients with type II diabetes was not associated with liver cancer, though there was a suggestion of a small protective effect for metformin.

Measles in the United Kingdom 1990-2008 and the effectiveness of measles vaccines.

We identified all children in the UK General Practice Research Database diagnosed with measles from 1990 to 2008 and calculated annual incidence according to age and geographic region by dividing the number of cases per year by the number of children who were active in the population. We evaluated the effectiveness of the measles vaccines by comparing the vaccination histories of children who were diagnosed with measles (cases) to children who were not (controls). The annual incidence of measles fell after the introduction of the MMR vaccine in late 1988. However, a modest outbreak of measles occurred in 1994, leading to large nationwide programs to immunize children. Since 1996, the incidence of measles has fallen by more than 80%. Prior measles vaccination is highly effective and has substantially reduced the risk of measles.

Rate of Suicide in Patients Taking Montelukast

Study Objective. To estimate the rate of suicide in patients taking montelukast.

Risk of erectile dysfunction associated with use of 5-α reductase inhibitors for benign prostatic hyperplasia or alopecia: population based studies using the Clinical Practice Research Datalink

Objective To estimate the risk of erectile dysfunction in men who used 5-α reductase inhibitors to treat benign prostatic hyperplasia or alopecia. Design Cohort studies with nested case-control analyses. Setting UK Clinical Practice Research Datalink. Population Two populations of men free of risk factors for erectile dysfunction and other sexual dysfunction or its treatment: men aged 40 or more with benign prostatic hyperplasia who received a prescription for a 5-α reductase inhibitor (finasteride or dutasteride) or α blocker, or both, and men aged 18-59 with alopecia. Exposures In the benign prostatic hyperplasia study, exposures were classified as 5-α reductase inhibitors only, 5-α reductase inhibitors+α blockers, or α blockers only. In the alopecia study, exposures were finasteride 1 mg or no treatment. Main outcome measures Cases were men with a diagnosis of erectile dysfunction or treatment (procedure or prescription for a phosphodiesterase type 5 inhibitor) during follow-up. We calculated incidence rates and adjusted incidence rate ratios with 95% confidence intervals. We also conducted nested case-control analyses to control for major confounders, and calculated adjusted odds ratios with 95% confidence intervals. Results In the population with benign prostatic hyperplasia (n=71 849), the risk of erectile dysfunction was not increased with use of 5-α reductase inhibitors only (incidence rate ratio 0.92, 95% confidence interval 0.85 to 0.99; odds ratio 0.94, 95% confidence interval 0.85 to 1.03) or 5-α reductase inhibitors+α blocker (1.09, 0.99 to 1.21, 0.92; 0.80 to 1.06) compared with α blockers only, and remained null regardless of number of prescriptions or timing of use. The risk of erectile dysfunction increased with longer duration of benign prostatic hyperplasia, regardless of exposure. For the alopecia population (n=12 346), the risk of erectile dysfunction was not increased for users of finasteride 1 mg compared with unexposed men with alopecia (1.03, 0.73 to 1.44; 0.95, 0.64 to 1.41). Conclusion 5-α reductase inhibitors do not seem to significantly increase the risk of incident erectile dysfunction, regardless of indication for use. Risk of erectile dysfunction increased with longer duration of benign prostatic hyperplasia.