Rationale and design of a European epidemiological post-authorization safety study (PASS) program: rivaroxaban use in routine clinical practice.

BACKGROUND: Rivaroxaban is a highly selective factor Xa inhibitor approved for use in Europe for multiple indications. STUDY DESIGN AND METHODS: The European rivaroxaban epidemiological post-authorization safety study (PASS) program consists of seven complementary observational studies. For four of the studies, data are obtained from health-care databases in the UK, the Netherlands, Germany, and Sweden. These database studies describe patterns of rivaroxaban use and patient characteristics over time, and investigate safety and effectiveness outcomes in new users of rivaroxaban using a cohort analysis and nested case-control analysis. To put these results in context, safety outcomes are also analyzed in new users of standard of care. In addition, a modified prescription event monitoring study conducted in the early post-launch phase in primary care, and two specialist cohort event monitoring studies that investigated rivaroxaban use in the secondary care hospital setting, systematically collected drug utilization and safety data via questionnaires completed by health-care professionals in the UK. DISCUSSION: The European rivaroxaban epidemiological PASS is a comprehensive program of complementary studies generating evidence from patients treated in routine clinical practice that will expand our understanding of the risk-benefit profile of rivaroxaban.

Age and sex related self-reported symptoms in a general population across 30 years: Patterns of reporting and secular trend.

OBJECTIVE: To study age and sex specific prevalence of 30 symptoms in random samples from the general population and to analyze possible secular trends across time. STUDY POPULATION: The study was based on data from eight on-going Swedish cohort studies, with baseline investigations performed between 1973 and 2003. Samples were drawn from the general population of the cities of Gothenburg and Eskilstuna, and of Uppsala County. Overall, 20,160 subjects were sampled, 14,470 (71.8%) responded, of whom 12.000 were unique subjects, and 2548 were part of more than one sample. METHODS: The Complaint score sub-scale of the Gothenburg Quality of Life instrument, listing 30 general symptoms was used. Responders were asked to indicate which symptoms they had experienced during the last three months. RESULTS: Women reported on average 7.8 symptoms, and men 5.3 (p<0.0001). Women reported higher prevalence than men for 24 of the 30 symptoms. In multivariate analyses four patterns of prevalence across age were identified in both men and women; increasing prevalence, decreasing, stable and biphasic prevalence. The symptoms in the various pattern groups differed somewhat between men and women. However, symptoms related to strain were prominent among symptoms decreasing with age. Moreover, there were secular trends. Across all symptoms reporting prevalence increased over time in men (p<0.001) as well as in women (p<0.0001). CONCLUSIONS: Women reported higher total symptom prevalence than men. Symptoms related to health generally increased with age, while symptoms related to stress decreased markedly. Significant secular trends across time regarding symptom prevalence were found.

The reporting and diagnosis of uterine fibroids in the UK: an observational study.

BACKGROUND: Uterine fibroids (UFs) are the most common benign tumour in women, and many undergo hysterectomy or uterus-preserving procedures (UPPs) to manage their symptoms. We aimed to validate the recording of UFs in a primary care database, The Health Improvement Network (THIN), and to determine the incidence of UFs in the UK. METHODS: In this observational study, women in THIN aged 15-54 years between January 2000 and December 2009 with no previous record of UFs, hysterectomy or UPPs were identified. Individuals were followed up until there was a Read code indicating UFs, they reached 55 years of age or died, or the study ended. Among those without a UF code, women were identified with a code for hysterectomy, UPPs or heavy menstrual bleeding (HMB). Anonymized patient profiles from each category were randomly selected and reviewed. Subsequently, primary care physicians were asked to complete questionnaires to verify the diagnosis for a randomly selected subgroup. RESULTS: In total, 737,638 women were identified who met the initial inclusion criteria. The numbers of women with a code for UFs, hysterectomy, UPPs and HMB were 9380, 11,002, 3220 and 60,915, respectively; the proportions of confirmed cases of UFs were 88.8, 29.7, 57.7 and 15.9 %. The estimated number of women with UFs was 23,140 (64.0 % without a recorded UF diagnosis). The overall incidence of UFs was 5.8 per 1000 woman-years. CONCLUSIONS: UFs were confirmed in a high proportion of women with UF Read codes. However, almost two-thirds of cases were identified among women with a code for hysterectomy, UPPs or HMB. These results show that UFs are under-recorded in UK primary care, and suggest that primary care physicians tend to code the symptoms of UFs more often than the diagnosis.

Prescribing patterns of combined hormonal products containing cyproterone acetate, levonorgestrel and drospirenone in the UK.

BACKGROUND: There are limited data to show the levels of prescribing of combined oral contraceptives (COCs) and other hormonal products containing estrogen/progestogen combinations that may be outside the product licence. AIMS: To determine the diagnosis/indication recorded at the time of prescription of cyproterone acetate/ethinylestradiol (CPA/EE) and two COCs, levonorgestrel/EE (LNG/EE) and drospirenone/EE (DRSP/EE). DESIGN AND SETTING: Retrospective study using a primary care database, The Health Improvement Network (THIN). METHODS: Women in THIN aged 12-49 years prescribed CPA/EE, LNG/EE or DRSP/EE in 2002-2010 were identified. Overall use of each product and proportion of new users each year were determined. Among new users, database codes were analysed to infer the reason for prescription. RESULTS: The proportion of new users of each product in 2002 and 2010, respectively, were: LNG/EE, 2.03% and 2.40%; CPA/EE, 0.45% and 0.27%; and DRSP/EE, 0.27% and 0.56%. Most new users prescribed CPA/EE had a record of acne (51.0% and 79.2% in 2002 and 2010, respectively) or hirsutism (3.0% and 5.0% in 2002 and 2010, respectively); the proportion of new users with a record only for contraception decreased from 32.9% in 2002 to 8.6% in 2010. Among new users prescribed DRSP/EE or LNG/EE in 2010, 43.2% and 30.8% of women, respectively, did not have a record indicating use for contraception. CONCLUSIONS: Adherence to prescribing guidelines for CPA/EE has improved over time. A substantial proportion of women using DRSP/EE or LNG/EE had records for hormone-responsive conditions only, suggesting that many women were prescribed these therapies for non-contraceptive use.

The incidence of hysterectomy, uterus-preserving procedures and recurrent treatment in the management of uterine fibroids.

OBJECTIVE: To determine the incidence of hysterectomy and uterus-preserving procedures (UPPs) among women with uterine fibroids (UFs) and the incidence of further procedures after a UPP. STUDY DESIGN: This was an observational study using a primary care database, The Health Improvement Network (THIN). Women in THIN with UFs aged 15-54 years between January 2000 and December 2009 were eligible for study. The UPPs examined were myomectomy, endometrial ablation (EA) and uterine artery embolization (UAE). Using Read codes, women were followed up until one of the following was met: there was a record of hysterectomy or UPPs, they died or the study ended (end of 2010). RESULTS: The cumulative incidence of hysterectomy or UPPs was 23.6% at 1 year, and 40.9% after the follow-up period (median 3.6 years). At the end of the follow-up period, the cumulative incidences of hysterectomy, myomectomy, EA and UAE were 33.0%, 3.9%, 6.4% and 1.9%, respectively. For women initially treated with a UPP, the cumulative incidence of second procedures was 11.5% at 1 year. At the end of the follow-up period (median 2.7 years), the cumulative incidence of further procedures was 26.1%, and the cumulative incidences of women undergoing hysterectomy, myomectomy, EA and UAE were 19.0%, 4.3%, 3.4% and 1.4%, respectively. CONCLUSIONS: Women considering UPPs for the management of UFs should be made aware that the incidence of further treatments is high, with hysterectomy being the most frequent procedure undergone.

The continuation rates of long-acting reversible contraceptives in UK general practice using data from The Health Improvement Network.

PURPOSE: The purpose of this study was to determine the continuation rates of new users of long-acting reversible contraceptive (LARC) methods in the UK, using data from general practice. METHODS: We conducted an observational study using a general practitioner (GP) database, The Health Improvement Network (THIN). The methods studied were copper intrauterine devices (Cu-IUDs), levonorgestrel-releasing intrauterine system (LNG-IUS), progestogen-only implants and progestogen-only injections. The study population comprised women in THIN aged 18-44 years during the period 2004-2009 who had been registered with their GP for at least 5 years, with a computerized prescription history of at least 1 year. Using computer algorithms, the database was searched for the Read and Multilex codes for each LARC method. New LARC users were identified and followed until there was a record indicating termination of use or the study period ended. RESULTS: The proportion of women who discontinued use during the same year of administration was 7.5% for Cu-IUDs, 10.6% for LNG-IUS, 13.2% for progestogen-only implants and 54.4% for progestogen-only injections. By the end of the study, a higher proportion of Cu-IUD and LNG-IUS users (21.1 and 18.6%, respectively) undertook consecutive use of the same method than progestogen-only implant users (10.7%). Manual review of computerized profiles demonstrated the validity of this approach. CONCLUSIONS: In the UK, the continuation rates of LARCs are high, and approximately one fifth of women chose to have a second intrauterine device fitted after expiry of the first device. A validation step demonstrated the reliability of the methodology and computer algorithms used.

Use of long-acting reversible contraceptives in the UK from 2004 to 2010: analysis using The Health Improvement Network Database.

OBJECTIVES: To determine the use of long-acting reversible contraceptives (LARCs) in the UK over the period 2004 to 2010, using the general practice database The Health Improvement Network (THIN). METHODS: Women in THIN, aged 18 to 44 years during 2004 to 2010, who had been registered with their general practitioner for at least five years, with a prescription history of at least one year were included. THIN was searched using the Read and MULTILEX codes for: copper intrauterine devices (Cu-IUDs), the levonorgestrel releasing-intrauterine system (LNG-IUS), progestogen-only implants, and progestogen-only injections. RESULTS: The prevalence of progestogen-only implant use rose from 0.5 to 3.4%, and that of the LNG-IUS from 3.1 to 5.2%. The annual incidence and prevalence of progestogen-only implant use increased for all age groups but was most marked in younger women, whereas the use of the LNG-IUS augmented with increasing age. For all women, there was a small decrease in the prevalence of use of Cu-IUDs (from 5.4 to 4.8%) and progestogen-only injections (from 3.6 to 3.2%). CONCLUSIONS: Uptake of progestogen-only implants and the LNG-IUS increased over the period 2004 to 2010 in the UK, but LARC use in young women remains low.

Use of rivaroxaban in Germany: a database drug utilization study of a drug started in hospital.

PURPOSE: The purpose of this drug utilization study was to describe the use of rivaroxaban in Germany during a time period in which approval was limited to the prevention of venous thromboembolism following hip or knee replacement. Additionally, we explored the feasibility of reconstructing inpatient drug use of rivaroxaban in a database where with a few exceptions inpatient prescribing information is not available. METHODS: Source of data was one statutory health insurance providing data on about seven million insurants throughout Germany. Analyses were based on a cohort of rivaroxaban users from launch (October 2008) to December 2009 and encompassed potential indications for rivaroxaban use, treatment duration, and co-prescribing of potentially interacting drugs. Start of rivaroxaban treatment was defined by the date of surgery. RESULTS: During the study period, 425 rivaroxaban users were identified contributing 440 treatment periods. For more than 82% of these episodes labelled indications could be determined. Treatment durations exceeded recommendations in 95% of the episodes following knee replacement whereas rivaroxaban use after elective hip surgery was found to be longer than recommended in 56%. Prescribing of potentially interacting medication was rare except for non-steroidal anti-inflammatory drugs. CONCLUSIONS: Overall, no important off-label use of rivaroxaban was identified. Based on several assumptions that have to be considered in the interpretation of the results our study describes a database approach to reconstruct inpatient drug use for a drug started after a coded hospital procedure, when treatment continues after hospital discharge and no change in drug use is expected in the outpatient setting.

Risk of acute liver injury associated with the use of moxifloxacin and other oral antimicrobials: a retrospective, population-based cohort study.

STUDY OBJECTIVE: To estimate the incidence and relative risk of a hospitalization or emergency visit for noninfectious liver injury in users of eight oral antimicrobials-amoxicillin, amoxicillin-clavulanic acid, clarithromycin, cefuroxime, doxycycline, levofloxacin, moxifloxacin, telithromycin-compared with nonusers of these antimicrobials. DESIGN: Retrospective, observational cohort study with a nested case-control analysis. DATA SOURCE: HealthCore Integrated Research Database. PATIENTS: Adults with continuous health plan enrollment for at least 6 months before study entry who had a new dispensing of a study antimicrobial between July 1, 2001, and March 31, 2009. Cases had diagnoses indicating noninfectious liver injury during follow-up. To control for potentially confounding risk factors, 10 controls at risk for liver injury during follow-up were matched to each case by age, sex, and event date (liver injury date of the case), and analyses were adjusted for medical history, concomitant drugs, and health care service use. MEASUREMENTS AND MAIN RESULTS: Two physician reviewers (blind to exposure) validated the cases. Among 1.3 million antimicrobial users, we identified 607 cases of liver injury, including 82 cases of severe hepatocellular injury and 11 cases of liver failure. Liver injury incidence in nonusers of study antimicrobials was 35/100,000 person-years (95% confidence interval [CI] 29-42/100,000 person-years). For valid cases, the adjusted relative risk among current users of multiple antimicrobials was 3.2 (95% CI 1.6-6.7). Levofloxacin had the highest relative risk for current single use (3.2, 95% CI 1.8-5.8). Relative risks were also elevated for amoxicillin-clavulanic acid (2.5, 95% CI 1.3-5.0), doxycycline (2.5, 95% CI 1.2-5.2), moxifloxacin (2.3, 95% CI 1.1-4.7), and amoxicillin (2.3, 95% CI 1.1-4.7). CONCLUSION: The results support a comparatively high adjusted relative risk of liver injury among patients exposed concurrently to multiple antimicrobials and modest elevations in the risk for several antimicrobials used alone; however, we found little evidence of any strong effect of commonly used antimicrobials on the risk of liver injury.

Study of long-acting reversible contraceptive use in a UK primary care database: validation of methodology.

OBJECTIVES To develop and validate algorithms to identify new users of long-acting reversible contraceptives (LARCs) in a primary care database, The Health Improvement Network (THIN). METHODS Women in THIN aged 12 to 49 years in 2005 were studied. THIN was searched using Read and MULTILEX codes to identify new users of copper intrauterine devices (Cu-IUDs), the levonorgestrel-releasing intrauterine system (LNG-IUS) and progestogen-only implants. Validation was undertaken for a randomly selected sample of 398 LARC users, in which their primary care physicians were asked to complete a questionnaire detailing LARC use. RESULTS Questionnaires were received for 379 patients (95%), confirming 316 (83%) as new LARC users. Confirmation rates for Cu-IUDs, the LNG-IUS and progestogen-only implants were 64%, 94% and 89%, respectively. The use of Read codes alone had the lowest confirmation rate, particularly for Cu-IUD users. Confirmation rates increased by using MULTILEX codes when available, or by examination of computerised medical records. CONCLUSIONS Computer algorithms were used to identify new LARC users. While THIN is a useful resource for studying LARC uptake, steps to gather additional information are necessary to ensure the validity of LARC classification.

Validation of acute liver injury cases in a population-based cohort study of oral antimicrobial users.

We conducted a cohort study of acute, noninfectious liver injury among oral antimicrobial users. Potential cases were identified in the HealthCore Integrated Research Database (HIRD(SM)) population between July 1, 2001, and March 31, 2009, using ICD-9-CM codes primarily for acute and subacute necrosis of the liver, hepatic coma, and unspecified hepatitis. Liver test results were used to confirm case status according to published criteria. Two physician reviewers experienced in studying acute liver injury (blinded to study drug exposures) evaluated data abstracted from hospital and emergency department records to validate potential cases. Of 715 potential cases having claims associated with any of the primary screening codes, 312 (44%) were valid cases, 108 (15%) were not cases, and 295 (41%) were of uncertain status (records inadequate for validation). Among potential cases with adequate medical records, the PPV for presence of any of the primary codes was 74% (95% CI, 70%-78%). The highest PPV for a single code was for acute and subacute necrosis of the liver (84%; 95% CI, 77%-90%). Evaluation of cases of noninfectious liver injury using hospital and emergency department medical records continues to represent the preferred approach in studies using insurance claims data.

Mortality after hemorrhagic stroke: data from general practice (The Health Improvement Network).

OBJECTIVE: To investigate short-term case fatality and long-term mortality after intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) using data from The Health Improvement Network database. METHODS: Thirty-day case fatality was stratified by age, sex, and calendar year after ICH and SAH using logistic regression. Cox proportional hazards regression analyses were used to estimate the risk of death during the first year of follow-up and survivors at 1 year. RESULTS: Case fatality after ICH was 42.0%, compared with 28.7% after SAH. It increased with age (ICH: 29.7% for 20-49 years, 54.6% for 80-89 years; SAH: 20.3% for 20-49 years, 56.7% for 80-89 years; both p-trend < 0.001), and decreased over the period 2000-2001 to 2006-2008 (ICH: from 53.1% to 35.8%, p-trend < 0.001; SAH: from 33.3% to 24.7%, p-trend = 0.02). Risk of death was significantly higher among stroke patients during the first year of follow-up compared with controls (ICH: hazard ratio [HR] 2.60, 95% confidence interval [CI] 2.09-3.24, p < 0.01; SAH: HR 2.87, 95% CI 2.07-3.97, p < 0.01) and remained elevated among survivors at 1 year (ICH: HR 2.02, 95% CI 1.75-2.32, p < 0.01; SAH: HR 1.32, 95% CI 1.02-1.69, p = 0.03). CONCLUSIONS: More than one-third of individuals die in the first month after hemorrhagic stroke, and patients younger than 50 years are more likely to die after ICH than SAH. Short-term case fatality has decreased over time. Patients who survive hemorrhagic stroke have a continuing elevated risk of death compared with matched individuals from the general population.

Incidence of hemorrhagic stroke in the general population: validation of data from The Health Improvement Network.

PURPOSE: The Health Improvement Network (THIN) is a UK healthcare database composed of computerized information from primary care physicians (PCPs). We analyzed the validity of our method for identifying cases of intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) within THIN and assessed the incidence of these events. METHODS: Patients aged 20-89 years were identified and followed until (i) ICH or SAH was detected, (ii) the patient reached 90 years old (iii) death, or (iv) the end of the study. Computerized patient profiles were reviewed manually; those not discarded became potential cases. A validation study was undertaken in 400 computer-detected cases (333 confirmed as potential cases; 67 discarded). PCPs completed a questionnaire to determine the actual incidence of ICH and SAH among these cases. We also assessed the incidence of ICH and SAH in the total cohort. RESULTS: A total of 4330 patients with a READ code suggesting hemorrhagic stroke were identified. Computerized profiles with free-text comments were reviewed manually to identify 3633 potential cases. Responses to the PCP questionnaire were received for 306 potential cases and 63 discarded cases (92% response rate); 82% of potential cases were confirmed. Finally, we identified 3137 cases of hemorrhagic stroke. Crude incidence was 15 per 100,000 person-years for ICH and 11 per 100,000 person-years for SAH; the overall incidence increased sharply with age. CONCLUSIONS: Computer detection of cases of hemorrhagic stroke in THIN followed by manual review of clinical profiles is a valid method. The incidence of hemorrhagic stroke increases sharply with age.

Epidemiology of meningioma in the United Kingdom.

BACKGROUND: Data on the epidemiology and aetiology of meningioma are limited. METHODS: The Health Improvement Network UK primary care database was used to ascertain incident cases of meningioma between January 1996 and June 2008. Ten thousand controls analysis were frequency-matched by age, sex and year. A nested case control analysis was performed to determine risk factors for meningioma. RESULTS: The incidence of meningioma was 5.30 per 100,000 person-years over the study period. The incidence was higher in women than in men (7.19 vs. 3.05 per 100,000 person-years). Cerebrovascular disease (OR 1.86; 95% CI 1.46-2.36) and a history of cancer, thyroid disease, epilepsy, migraine and headache and exposure to antiepileptics were significantly associated with an increased risk of meningioma. Ischemic heart disease and exposure to antiepileptics were associated with a decreased risk of meningioma. CONCLUSIONS: The incidence of meningioma in the UK remained stable over the 12-year study period and was twofold higher in women than men. Although the prevalence and incidence of meningioma remained stable during the study, further research into risk factors and predisposing conditions for the onset of meningioma and early symptoms of tumor development is warranted to improve prevention and early diagnosis of this disease.

Hormonal therapies and meningioma: is there a link?

BACKGROUND: The aetiology of meningiomas is largely unknown although hormones have been suggested to play a role. METHODS: A cohort study was performed to evaluate hormone-related factors associated with meningioma. Patients (12-89 years) with a first diagnosis of meningioma (January 1996-June 2008) were identified from The Health Improvement Network UK primary care database and age- and sex-matched to controls (n=10000) from the same cohort. Odds ratios (ORs) were calculated following a nested case control analysis using unconditional logistic regression. RESULTS: In total, 745 patients with meningioma were identified from a study population of 2171287. No significantly increased risk of meningioma was found among female users of oral contraceptives (OR: 1.15; CI: 0.67-1.98), hormone replacement therapy (OR: 0.99; CI: 0.73-1.35) or low-dose cyproterone acetate (CPA; OR: 1.51; CI: 0.33-6.86) compared with non-users. There was a significantly increased risk of meningioma among male users of androgen analogues (OR: 19.09; CI: 2.81-129.74) and among users of high-dose CPA (OR: 6.30; CI: 1.37-28.94) compared with non-users, however there were only three cases currently using these drugs. No significant association was found between meningioma and prostate, breast, or genital cancers. CONCLUSIONS: Our results do not support a role for exogenous hormone use by females in meningioma development. The risk in males was only observed with high-dose, short-term (<1 year) therapy. IMPACT: While hormonal cancers and therapies are not associated with meningioma in females, the risk in males requires further investigation.

Treatment patterns in paediatric patients with a new diagnosis of gastroesophageal reflux disease.

OBJECTIVE: Few data exist on the treatment of gastroesophageal reflux disease (GERD) in paediatrics. The objective of this study was to examine treatment patterns of GERD in paediatrics in the primary care. METHODS: Incident GERD cases among paediatric patients were identified using The Health Improvement Network UK primary care database. We assessed prescription treatments in 30 days before and any time after the date of diagnosis. Initial treatment was defined as that received in 30 days either side of diagnosis. Odds ratios and 95% confidence intervals of receiving the treatment were calculated by multiple logistic regressions. RESULTS: The incident GERD cohort comprised 1700 paediatric patients aged 1-17 years. Antacids were initially prescribed in 49.2% of patients. Similar proportions of patients (23.3 and 22.9%) received histamine-2 receptor antagonists (H(2)RAs) and proton pump inhibitors (PPIs); 7.5% were prescribed prokinetics and 19.3% received no prescribed treatment. Overall, 24.7% of initial H(2)RA users switched to PPIs, and 9.8% of those using PPIs switched to H(2)RAs. The likelihood of the use of PPI increased with age and was lower in girls than in boys (odds ratio: 0.7; 95% confidence interval: 0.5-0.9). CONCLUSIONS: Antacids are the drugs most frequently prescribed by primary care physicians to paediatric patients with GERD, and approximately half receive an initial course of antisecretory treatment with H(2)RAs or PPIs. This study suggests that treatment patterns in paediatrics differ from those in adults.

A population-based survey of the epidemiology of symptom-defined gastroesophageal reflux disease: the Systematic Investigation of Gastrointestinal Diseases in China.

BACKGROUND: The epidemiology of gastroesophageal reflux disease (GERD) has yet to be investigated using the symptomatic threshold criteria recommended by the Montreal Definition. This study aimed to determine the prevalence of symptom-defined GERD across five regions of China, and to investigate variables associated with GERD. METHODS: A representative sample of 18 000 adults (aged 18-80 years) were selected equally from rural and urban areas in each region (n = 1800). According to the Montreal Definition, GERD is present when mild symptoms of heartburn and/or regurgitation occur on >or=2 days a week, or moderate-to-severe symptoms of heartburn and/or regurgitation occur on >or=1 day a week. RESULTS: In total, 16 091 participants completed the survey (response rate: 89.4%) and 16 078 responses were suitable for analysis. Applying the Montreal criteria, the prevalence of symptom-defined GERD was 3.1% and varied significantly (p < 0.001) among the five regions (from 1.7% in Guangzhou to 5.1% in Wuhan) and between rural and urban populations (3.8% vs 2.4%). Factors significantly associated with GERD included living in a rural area and a family history of gastrointestinal diseases. CONCLUSIONS: This population-based survey found that the prevalence of symptom-defined GERD in China was 3.1%, which is lower than that found in Western countries.

Study of a cohort of patients newly diagnosed with depression in general practice: prevalence, incidence, comorbidity, and treatment patterns.

OBJECTIVE: To estimate the prevalence and incidence of depression; investigate its association with risk factors including comorbidities and drug and health care use; and describe treatment patterns of depression in primary care using The Health Improvement Network database. METHOD: In this cohort study, subjects with a first recorded diagnosis of depression (Read code) between January 1, 2002, and December 31, 2004 (n=47,170) were identified from a source population of 1,287,829 subjects aged 10-79 years. A comparison group was sampled from the same population and frequency matched to the depression cohort by age, sex, and calendar year (n=50,000). Depression diagnoses were validated using physician-completed questionnaires. Odds ratios and 95% CIs for the relationship of depression with a range of factors were estimated using unconditional logistic regression in a nested case-control analysis. RESULTS: The prevalence of depression was 11.23% (95% CI, 11.18-11.28). This prevalence decreased with increasing age and was higher in women than in men. The incidence was 13.89 per 1,000 person-years (95% CI, 13.82-14.08). Depression was associated with frequent use of health services, smoking, pregnancy in the previous year, anxiety, stress, sleep disorders, digestive and respiratory disorders, and pain. In the trimester following diagnosis, 82% of cases were treated-98% with antidepressants and 81.5% with selective serotonin reuptake inhibitors (SSRIs). CONCLUSIONS: We found a high prevalence and incidence of depression diagnoses in primary care in the United Kingdom. Following diagnosis, the majority of individuals were prescribed SSRIs. A diagnosis of depression is associated with a number of prior comorbidities, which could mask the depression. This fact should be taken into account when screening individuals in primary care.

Heart failure, myocardial infarction, lung cancer and death in COPD patients: a UK primary care study.

BACKGROUND: The leading comorbidities and causes of death in patients with chronic obstructive pulmonary disease (COPD) are lung cancer and cardiovascular disease. The aim of this study was to establish the incidence of lung cancer, myocardial infarction and heart failure in patients with COPD in UK primary care. METHODS: The General Practice Research Database (GPRD) was used to identify a cohort of 1927 patients with a first recorded diagnosis of COPD. This cohort was followed for up to 5 years to identify new diagnoses of lung cancer, myocardial infarction and heart failure. Mortality was also assessed. The relative risk (RR) of each outcome in the COPD cohort was compared with that in a control cohort with no diagnosis of COPD. RESULTS: The risk of lung cancer was significantly increased in individuals with a diagnosis of COPD compared with those with no COPD diagnosis (RR: 3.33; 95% confidence interval [CI]: 2.33-4.75; adjusted for age, sex and smoking status). A diagnosis of COPD was also associated with a significant increase in the risk of heart failure (age- and sex-adjusted RR: 2.94; 95% CI: 2.46-3.51) and death (age- and sex-adjusted RR: 2.76; 95% CI: 2.45-3.12), but not myocardial infarction (age- and sex-adjusted RR: 1.18; 95% CI: 0.81-1.71). CONCLUSIONS: Patients with a diagnosis of COPD are at significantly increased risk of lung cancer, heart failure and death compared with the general population. They do not appear to be at increased risk of myocardial infarction.

Follow-up of a cohort of children and adolescents with gastro-esophageal reflux disease who were free of reflux esophagitis at initial diagnosis.

OBJECTIVE: Few studies have examined the incidence of complications from gastro-esophageal reflux disease (GERD) in children and adolescents in primary care. Here we aimed to describe the natural history of GERD in a pediatric population with no reflux esophagitis at initial diagnosis, assessing diagnoses of new esophageal complications and extra-esophageal conditions. MATERIAL AND METHODS: We used The Health Improvement Network UK primary care database (which includes data on more than 2 million patients) to identify individuals aged 1-17 years with a first diagnosis of gastro-esophageal reflux or heartburn in the period 2000-2005, via a computerized search followed by a manual review of the patient records. This search identified 1242 individuals with an incident diagnosis of GERD but no record of esophagitis. This cohort was followed-up to detect new diagnoses of esophageal complications and extra-esophageal conditions. RESULTS: During a mean follow-up period of almost 4 years, 40 children and adolescents had a confirmed new diagnosis of reflux esophagitis (incidence: 10.9 per 1000 person-years). No cases of Barrett's esophagus, esophageal stricture or esophageal ulcer were reported. Individuals with GERD had double the risk of an extra-esophageal condition such as asthma, pneumonia, cough or chest pain compared with children and adolescents with no diagnosis of GERD. CONCLUSIONS: Children and adolescents with GERD may be at risk of developing reflux esophagitis and a range of other extra-esophageal conditions, but more severe esophageal complications are rare.