Publications
scientifiques

BACKGROUND: Exacerbations of chronic obstructive pulmonary disease (COPD) are a burden to patients and impose a major cost on health services. Long-term antibiotic therapy may prevent exacerbations, but at present it is not recommended by management guidelines. AIMS: To identify the type and prevalence of long-term oral antibiotic treatments prescribed to patients with COPD and to assess the patient characteristics associated with long-term antibiotic use. METHODS: A retrospective cohort using all eligible practices in The Health Improvement Network (THIN) UK primary care database between 2000 and 2009 was studied. We identified patients with COPD and then those who received a course of long-term antibiotics. Long-term courses were defined as >6 months in duration with <50% concomitant oral corticosteroid treatment. RESULTS: We identified 92,576 patients with COPD, but only 567 patients (0.61%) who received 998 long-term antibiotic courses. Mean follow-up time was 3 years and 10 months. The median long-term antibiotic course length was 280 days (interquartile range 224, 394) and 58 patients (0.06%) were continuously prescribed antibiotics for >2 years. The most commonly used long-term antibiotics were oxytetracycline, doxycycline, and penicillin. Azithromycin, erythromycin, and clarithromycin were less frequently used. There was little evidence of the use of rotating courses of antibiotics. Men, people aged 50-79 years, non-smokers, and patients with poorer lung function were more likely to receive long-term antibiotic treatment. CONCLUSIONS: Relatively few COPD patients are currently prescribed long-term antibiotics. Further clinical trials are required to determine the efficacy of this therapy. If beneficial, the use of such treatments should be incorporated into clinical guidelines.

OBJECTIVES: We aimed to examine the temporal association between selective serotonin reuptake inhibitors (SSRI) and tricyclic antidepressant (TCA) prescriptions and suicide-related events in children and adolescents. DESIGN: Self-controlled case series. SETTING: Electronic health records were used from 479 general practices in The Health Improvement Network (THIN) UK primary care database from 1995 to 2009. PARTICIPANTS: 81 young people aged 10-18 years with a record of completed suicide, 1496 who attempted suicide, 1178 with suicidal ideation and 2361 with intentional self-harm. MAIN OUTCOME MEASURES: Incidence Rate Ratios (IRRs) for completed and attempted suicide, suicidal ideation and intentional self-harm. RESULTS: For non-fatal suicide-related behaviour, IRRs were similar for the time the person was prescribed either SSRIs or TCAs: IRRs increased during pre-exposure, peaked on prescription day, were stable up to the fourth prescription-week, and decreased after the prescriptions were stopped. For both types of antidepressants, IRRs were lower or similar to pre-exposure levels during the period of prescription. For SSRIs, there was an increase in the IRR for completed suicide on the day of prescription (N=5; IRR=42.5, 95% CI 4.5 to 403.4), and during the fourth week of SSRI prescription (N=2; IRR=11.3, 95% CI 1.1 to 115.6). CONCLUSIONS: We found that a very small number of young people were prescribed antidepressants and that there was an absence of a sustained increase in rates of suicide-related events in this group. There were no systematic differences between the association of TCAs and SSRIs and the incidence risk ratios for attempted suicide, suicidal ideation or intentional self-harm and, apart from the day of prescription, rates did not exceed pre-exposure levels. The pattern of IRR for suicide for SSRIs was similar to that found in non-fatal suicide-related events. Our results warrant a re-evaluation of the current prescription of SSRIs in young people. We recommend the creation of a pragmatic registry for active pharmacovigilance.

OBJECTIVE: To evaluate the role of compression in non-healing venous leg ulcers (VLUs) of > 3 months' duration. METHOD: Patients' records from three independent data sets of non-healing VLUs of > 3 months'duration were re-analysed.Two data sets were separate audits of clinical practice and the third comprised patients' records from a randomised controlled trial. Some patients in each data set were never treated with compression. The effect of compression on healing at 6 months was tested with logistic regression. RESULTS: In each data set, patients in the compression and no-compression groups were matched according to ulcer size and duration; there were no differences in comorbidities. Comparing the no-compression with the compression groups, the healing rate at 6 months was 68% vs 48% in study 1, 12% vs 6% in study 2, and 26% vs 11% in study 3. Use of compression was found to be an independent predictor of not healing with an odds ratio of 0.422, 0.456 and 0.408 in studies 1, 2 and 3 respectively. CONCLUSION: The healing rate of non-healing VLUs of > 3 months' duration in the no-compression groups was double that of VLUs in the compression groups. These findings have the potential for treatment modification if confirmed in a prospective trial. DECLARATION OF INTEREST: There were no external sources of funding for this study. The authors have no conflicts of interest that are directly relevant to the content of this manuscript, which remains their sole responsibility.

BACKGROUND: Despite its rarity, the prognosis of pancreatic cancer is very poor and it is a major cause of cancer mortality; being ranked fourth in the world, it has one of the worst survival rates of any cancer. AIM: To evaluate the performance of QCancer(®) (Pancreas) for predicting the absolute risk of pancreatic cancer in an independent UK cohort of patients, from general practice records. DESIGN AND SETTING: Prospective cohort study to evaluate the performance QCancer (Pancreas) prediction models in 364 practices from the UK, contributing to The Health Improvement Network (THIN) database. METHOD: Records were extracted from the THIN database for 2.15 million patients registered with a general practice surgery between 1 January 2000 and 30 June 2008, aged 30-84 years (3.74 million person-years), with 618 pancreatic cancer cases. Pancreatic cancer was defined as incident diagnosis of pancreatic cancer during the 2 years after study entry. RESULTS: The results from this independent and external validation of QCancer (Pancreas) demonstrated good performance data on a large cohort of general practice patients. QCancer (Pancreas) had very good discrimination properties, with areas under the receiver operating characteristic curve of 0.89 and 0.92 for females and males respectively. QCancer (Pancreas) explained 60% and 67% of the variation in females and males respectively. QCancer (Pancreas) over-predicted risk in both females and males, notably in older patients. CONCLUSION: QCancer (Pancreas) is potentially useful for identifying undetected cases of pancreatic cancer in primary care in the UK.

BACKGROUND: Given the health impacts of smoking during pregnancy and the opportunity for primary healthcare teams to encourage pregnant smokers to quit, our primary aim was to assess the completeness of gestational smoking status recording in primary care data and investigate whether completeness varied with women's characteristics. As a secondary aim we assessed whether completeness of recording varied before and after the introduction of the Quality and Outcomes Framework (QOF). METHODS: In The Health Improvement Network (THIN) database we calculated the proportion of pregnancies ending in live births or stillbirths where there was a recording of maternal smoking status for each year from 2000 to 2009. Logistic regression was used to assess variation in the completeness of maternal smoking recording by maternal characteristics, before and after the introduction of QOF. RESULTS: Women had a record of smoking status during the gestational period in 28% of the 277,552 pregnancies identified. In 2000, smoking status was recorded in 9% of pregnancies, rising to 43% in 2009. Pregnant women from the most deprived group were 17% more likely to have their smoking status recorded than pregnant women from the least deprived group before QOF implementation (OR 1.17, 95% CI 1.10-1.25) and 42% more likely afterwards (OR 1.42, 95% CI 1.37-1.47). A diagnosis of asthma was related to recording of smoking status during pregnancy in both the pre-QOF (OR 1.63, 95% CI 1.53-1.74) and post-QOF periods (OR 2.08, 95% CI 2.02-2.15). There was no association between having a diagnosis of diabetes and recording of smoking status during pregnancy pre-QOF however, post-QOF diagnosis of diabetes was associated with a 12% increase in recording of smoking status (OR 1.12, 95% CI 1.05-1.19). CONCLUSION: Recording of smoking status during pregnancy in primary care data is incomplete though has improved over time, especially after the implementation of the QOF, and varies by maternal characteristics and QOF-incentivised morbidities.

PURPOSE: This paper aimed to assess the prescription of medications during pregnancy by primary care physicians in the UK. METHODS: We identified both completed pregnancies and pregnancies losses (ectopic pregnancies, miscarriages, terminations, and stillbirths) in women aged 13-49 years enrolled in The Health Improvement Network (THIN) between 1996 and 2010 following an algorithm with three sequential cycles that searched for Read Code groups in hierarchical order: (1) indicators of conception; (2) delivery or pregnancy loss; and (3) other codes suggestive of pregnancy. Completed pregnancies were linked to liveborn infants by means of the family identification number and date of birth. Prescription of specific drugs during the first trimester and time trends during the last decade were calculated. RESULTS: A total of 191 000 pregnancies were identified, including 148 544 completed pregnancies and 42 456 (22.2%) pregnancies losses (ectopic pregnancies, miscarriages, terminations, and stillbirths). Of the completed pregnancies, 131670 (88.6%) were successfully linked with the offspring. The most commonly prescribed drugs were antibiotics, antimycotics, asthma/allergy medications, and analgesics. From 1996 to 2010, the proportion of completed pregnancies with at least one prescription during the first trimester increased for antidepressants (1.8% to 4.2%), thyroid hormones (0.7% to 1.6%), and opiods (1.5% to 2.6%), among other drugs. CONCLUSION: In conclusion, the prescription of several medications by primary care physicians during the first trimester of pregnancy has risen in the UK during the last decade. We discuss how, when important challenges are considered, THIN may be a promising resource to study specific therapies during pregnancy.

OBJECTIVE: To investigate the relationship between hemorrhagic stroke and use of antiplatelets and warfarin using data from The Health Improvement Network. METHODS: A total of 1,797 incident cases of intracerebral hemorrhage (ICH) and 1,340 of subarachnoid hemorrhage (SAH) were ascertained. Density-based sampling was used to select 10,000 controls free from hemorrhagic stroke. Risk of hemorrhagic stroke was evaluated in current users and nonusers of antiplatelets and warfarin. Unconditional logistic regression models were used to adjust for age, sex, calendar year, alcohol, body mass index, hypertension, and health services utilization. RESULTS: Aspirin use was not associated with an increased risk of ICH (odds ratio [OR] 1.06, 95% confidence interval [CI] 0.93-1.21), but was associated with a decreased risk of SAH (OR 0.82, 95% CI 0.67-1.00), compared with no therapy. Aspirin use ≥3 years was associated with a decreased risk of SAH (OR 0.63, 95% CI 0.45-0.90) compared with no therapy. Warfarin use was associated with a greatly increased risk of ICH (OR 2.82, 95% CI 2.26-3.53) and a moderately increased risk of SAH (OR 1.67, 95% CI 1.15-2.43) compared with no therapy. International normalized ratio values ≥3 carried a marked risk of ICH (OR 7.01, 95% CI 4.10-11.99). CONCLUSION: Aspirin is not associated with a risk of ICH compared with no therapy. Chronic low-dose aspirin treatment may have a protective effect on the risk of SAH. Warfarin users in this study cohort were at a much higher risk of ICH than those receiving no therapy, with a marked association with international normalized ratio >3.

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.

BACKGROUND: General practice data provide large population-based cohorts of individuals with prospectively collected medical information with promising potential for studying the causes and consequences of congenital anomalies (CAs). We sought to validate these data through comparison with CA registries. METHODS: Our study population was 794,209 children in The Health Improvement Network (THIN) primary care database, born between 1990 and 2009 with a median follow-up of 6.7 years. We compared the birth prevalence of any major and system-specific CAs with the European Surveillance of Congenital Anomalies (EUROCAT) United Kingdom registries. RESULTS: The birth prevalence of any major CA for children in THIN diagnosed before 1 year of age was 198 per 10,000 (95% confidence interval, 195-201), which was slightly higher than the EUROCAT prevalence of 167 per 10,000 (relative risk, 1.18; 95% confidence interval, 1.16-1.20). Absolute differences in prevalence between THIN and EUROCAT were small across 16 system-specific anomaly groups. The majority of children in THIN with major CAs had recorded diagnoses before 1 year of age (72%), but including children diagnosed at any age increased the overall prevalence to 277 per 10,000 births. CONCLUSION: The prevalence of CAs in THIN was consistent with EUROCAT for early diagnoses, demonstrating THIN to be a valuable source of data in which to investigate CAs. Age of diagnosis is an important factor in explaining a higher overall prevalence in THIN; the inclusion of diagnoses made after 1 year of age substantially improves capture of diagnoses.

BACKGROUND: In the UK, referrals to specialists are initiated by general practitioners (GPs). Study objectives were to estimate the incidence of diagnosed psoriasis in the UK and identify factors associated with GP referrals to dermatologists. METHODS: Newly diagnosed patients with psoriasis were identified in The Health Improvement Network (THIN) database between 01 July 2007-31 Oct 2009. Incidence of diagnosed psoriasis was calculated using the number of new psoriasis patients in 2008 and the mid-year total patient count for THIN in 2008. A nested case-control design and conditional logistic regression were used to identify factors associated with referral. RESULTS: Incidence rate of diagnosed adult psoriasis in 2008 was 28/10,000 person-years. Referral rate to dermatologists was 18.1 (17.3-18.9) per 100 person-years. In the referred cohort (N=1,950), 61% were referred within 30 days of diagnosis and their median time to referral was 0 days from diagnosis. For those referred after 30 days (39%, median time to referral: 5.6 months), an increase in the number of GP visits prior to referral increased the likelihood of referral (OR=1.87 95% CI:1.73-2.01). A prescription of topical agents such as vitamin D3 analogues 30 days before referral increased the likelihood of being referred (OR=4.67 95% CI: 2.78-7.84), as did corticosteroids (OR=2.45 95% CI: 1.45-4.07) and tar products (OR=1.95 95% CI: 1.02-3.75). CONCLUSIONS: Estimates of the incidence of diagnosed adult psoriasis, referral rates to dermatologists, and characteristics of referred patients may assist in understanding the burden on the UK healthcare system and managing this population in primary and secondary care.

AIMS: To quantify the extent to which smokers with indicators of poor mental health receive smoking cessation support in primary care consultations compared with those without. DESIGN: Cross-sectional study within a database of electronic primary care medical records. SETTING: A total of 495 general practices in the United Kingdom contributing data to The Health Improvement Network (THIN) database. PARTICIPANTS: A total of 2 493 085 patients aged 16+ registered with a THIN practice for the year from 1 July 2009 to 30 June 2010. MEASUREMENTS: The proportion of patients with a diagnostic Read code or British National Formulary (BNF) drug code indicating a mental health diagnosis or psychoactive medication prescription, respectively, who smoke and who have cessation advice or a smoking cessation medication prescription recorded during consultations within the 1-year study period. FINDINGS: Of 32 154 smokers, 50.6% [95% confidence interval (CI): 50.0-51.2] with a mental health diagnosis and 49.3% (95% CI: 49.0-49.7) of 96 285 smokers prescribed a psychoactive medication had a record of cessation advice, higher than the prevalence of advice recording in smokers without these indicators (33.4%, 95% CI: 33.3-33.6). Similarly, smoking cessation medication prescribing was higher: 11.2% (95% CI: 10.8-11.6) of smokers with a mental health diagnosis and 11.0% (95% CI: 10.8-11.2) of smokers prescribed psychoactive medication received a prescription, compared with 6.73% of smokers without these indicators (95% CI: 6.65-6.81). Smoking cessation support was offered in a lower proportion of consultations for smokers with indicators of poor mental health than for those without. Advice was recorded in 7.9% of consultations with smokers with a mental health diagnosis, 8.2% of consultations with smokers prescribed psychoactive medication and 12.3% of consultations with smokers without these indicators; comparable figures for prescribing of cessation medication were 2.9%, 3.2% and 4.4%, respectively. CONCLUSIONS: Approximately half of smokers with indicators of poor mental health receive advice to quit during primary care consultations in the United Kingdom, and one in 10 receive a cessation medication. Interventions are lower per consultation for smokers with mental health indicators compared with smokers without mental health indicators.

BACKGROUND: Recent studies suggest that the incidence of idiopathic pulmonary fibrosis (IPF) is rising. Accurate epidemiological data on IPF, however, are sparse and the results of previous studies are contradictory. This study was undertaken to gain insight into the various methods used in the epidemiological research of IPF, and to get accurate and comparable data on these different methodologies. METHODS: A systematic database search was performed in order to identify all epidemiological studies on IPF after the previous guidelines for diagnosis and treatment were published in 2000. Medline (via Pubmed), Science Sitation Index (via Web of Science) and Embase databases were searched for original epidemiological articles published in English in international peer-reviewed journals starting from 2001. After pre-screening and a full-text review, 13 articles were accepted for data abstraction. RESULTS: Three different methodologies of epidemiological studies were most commonly used, namely: (1) national registry databases, (2) questionnaire-based studies, and (3) analysis of the health care system's own registry databases. The overall prevalence and incidence of IPF varied in these studies between 0.5-27.9/100,000 and 0.22-8.8/100,000, respectively. According to four studies the mortality and incidence of IPF are rising. CONCLUSIONS: We conclude that there are numerous ways to execute epidemiological research in the field of IPF. This review offers the possibility to compare the different methodologies that have been used, and this information could form a basis for future studies investigating the prevalence and incidence of IPF.

BACKGROUND: Dementia is one of the most disabling and burdensome diseases. Incontinence in people with dementia is distressing, adds to carer burden, and influences decisions to relocate people to care homes. Successful and safe management of incontinence in people with dementia presents additional challenges. The aim of this study was to investigate the rates of first diagnosis in primary care of urinary and faecal incontinence among people aged 60-89 with dementia, and the use of medication or indwelling catheters for urinary incontinence. METHODS AND FINDINGS: We extracted data on 54,816 people aged 60-89 with dementia and an age-gender stratified sample of 205,795 people without dementia from 2001 to 2010 from The Health Improvement Network (THIN), a United Kingdom primary care database. THIN includes data on patients and primary care consultations but does not identify care home residents. Rate ratios were adjusted for age, sex, and co-morbidity using multilevel Poisson regression. The rates of first diagnosis per 1,000 person-years at risk (95% confidence interval) for urinary incontinence in the dementia cohort, among men and women, respectively, were 42.3 (40.9-43.8) and 33.5 (32.6-34.5). In the non-dementia cohort, the rates were 19.8 (19.4-20.3) and 18.6 (18.2-18.9). The rates of first diagnosis for faecal incontinence in the dementia cohort were 11.1 (10.4-11.9) and 10.1 (9.6-10.6). In the non-dementia cohort, the rates were 3.1 (2.9-3.3) and 3.6 (3.5-3.8). The adjusted rate ratio for first diagnosis of urinary incontinence was 3.2 (2.7-3.7) in men and 2.7 (2.3-3.2) in women, and for faecal incontinence was 6.0 (5.1-7.0) in men and 4.5 (3.8-5.2) in women. The adjusted rate ratio for pharmacological treatment of urinary incontinence was 2.2 (1.4-3.7) for both genders, and for indwelling urinary catheters was 1.6 (1.3-1.9) in men and 2.3 (1.9-2.8) in women. CONCLUSIONS: Compared with those without a dementia diagnosis, those with a dementia diagnosis have approximately three times the rate of diagnosis of urinary incontinence, and more than four times the rate of faecal incontinence, in UK primary care. The clinical management of urinary incontinence in people with dementia with medication and particularly the increased use of catheters is concerning and requires further investigation. Please see later in the article for the Editors' Summary.

OBJECTIVE: To examine whether gender differences in primary care consultation rates (1) vary by age and deprivation status and (2) diminish when consultation for reproductive reasons or common underlying morbidities are accounted for. DESIGN: Cross-sectional study of a cohort of patients registered with general practice. SETTING: UK primary care. SUBJECTS: Patients (1 869 149 men and 1 916 898 women) registered with 446 eligible practices in 2010. PRIMARY OUTCOME MEASURES: Primary care consultation rate. RESULTS: This study analyses routinely collected primary care consultation data. The crude consultation rate was 32% lower in men than women. The magnitude of gender difference varied across the life course, and there was no 'excess' female consulting in early and later life. The greatest gender gap in primary care consultations was seen among those aged between 16 and 60 years. Gender differences in consulting were higher in people from more deprived areas than among those from more affluent areas. Accounting for reproductive-related consultations diminished but did not eradicate the gender gap. However, consultation rates in men and women who had comparable underlying morbidities (as assessed by receipt of medication) were similar; men in receipt of antidepressant medication were only 8% less likely to consult than women in receipt of antidepressant medication (relative risk (RR) 0.916, 95% CI 0.913 to 0.918), and men in receipt of medication to treat cardiovascular disease were just 5% less likely to consult (RR=0.950, 95% CI 0.948 to 0.952) than women receiving similar medication. These small gender differences diminished further, particularly for depression (RR=0.950, 95% CI 0.947 to 0.953), after also taking account of reproductive consultations. CONCLUSIONS: Overall gender differences in consulting are most marked between the ages of 16 and 60 years; these differences are only partially accounted for by consultations for reproductive reasons. Differences in consultation rates between men and women were largely eradicated when comparing men and women in receipt of medication for similar underlying morbidities.

Early identification of ovarian cancer is an unresolved challenge and the predictive value of single symptoms is limited. We evaluated the performance of QCancer(®) (Ovarian) prediction model for predicting the risk of ovarian cancer in a UK cohort of general practice patients. A total of 1.1 million patients registered with a general practice surgery between 1 January 2000 and 30 June 2008, aged 30-84 years with 735 ovarian cancer cases, were included in the analysis. Ovarian cancer was defined as incident diagnosis of ovarian cancer during the 2 years after study entry. The results from this independent and external validation of QCancer(®) (Ovarian) prediction model demonstrated good performance on a large cohort of general practice patients. QCancer(®) (Ovarian) had very good discrimination with an area under the receiver operating characteristic curve of 0.86 and explained 59.9% of the variation. QCancer(®) (Ovarian) was well calibrated across all tenths of risk and over all age. The 10% of women with the highest predicted risks included 64% of all ovarian cancer diagnoses over the next 2 years. QCancer(®) (Ovarian) appears to be a useful tool for identifying undetected cases of ovarian cancer in primary care in the UK for early referral and investigation.