Publications
scientifiques

BACKGROUND: To describe patterns of antibiotic outpatient use in 3 European countries, including 2 new pediatric-specific quality indicators (QIs). METHODS: A cohort study was conducted, 2001-2010, using electronic primary care records of 2,196,312 children up to 14 (Pedianet, Italy) or 18 years (The Health Improvement Network, United Kingdom; Integrated Primary Care Information database, The Netherlands) contributing 12,079,620 person-years. Prevalence rates of antibiotic prescribing per year were calculated and antibiotics accounting (drug utilization) for 90% of all antibiotic prescriptions were identified (drug utilization 90% method). The ratio between users of broad to narrow-spectrum penicillins, cephalosporins and macrolides (B/N ratio) and 2 pediatric-specific QIs: the proportion of amoxicillin users (amoxicillin index) and the ratio between users of amoxicillin to broad-spectrum penicillins, cephalosporins and macrolides (A/B ratio) were determined. RESULTS: The overall annual prevalence of antibiotic prescriptions was 18.0% in the Netherlands, 36.2% in the United Kingdom and 52.0% in Italy. Use was maximal in the first years of life. The number of antibiotics accounting for the drug utilization 90% was comparable. The B/N ratio varied widely from 0.3 to 74.7. The amoxicillin index was highest in the Netherlands and the United Kingdom (50-60%), lowest in Italy (30%) and worsened over time in the United Kingdom and Italy. The A/B ratio in 2010 was 0.3 in Italy, 1.7 in the Netherlands and 5.4 in the United Kingdom. CONCLUSIONS: The patterns of antibiotic prescribing varied highly with age and country. The pediatric-specific QIs combined with the total prevalence rate of use provide a clear picture of the trends of community childhood antibiotic prescribing, allowing monitoring of the impact of policy interventions.

BACKGROUND: Poisonings are a common cause of morbidity and mortality among adolescents. Yet surveillance data indicating current incidence rates (IRs) and time trends are lacking, making policy development and service planning difficult. We utilised population based primary care data to estimate adolescent poisoning rates according to intent across the UK. METHODS: A cohort study of 1 311 021 adolescents aged 10-17 years, between 1992 and 2012, was conducted using routine primary care data from The Health Improvement Network. IRs and adjusted IRRs with 95% CIs were calculated for all poisonings, intentional, unintentional, unknown intent and alcohol related poisonings, by age, sex, calendar time and socioeconomic deprivation. RESULTS: Overall poisoning incidence increased by 27% from the period 1992-1996 to 2007-2012, with the largest increases in intentional poisonings among females aged 16-17 years (IR 391.4/100 000 person years (PY), CI 328.9 to 465.7 for age 17 years in 1992-1996; 767.0/100 000 PY, CI 719.5 to 817.7 in 2007-2012) and alcohol related poisonings in females aged 15-16 years (IR 65.7/100 000 PY, CI 43.3 to 99.8 rising to 130.0/100 000 PY, CI 110.0 to 150.0 for age 15 years). A strong socioeconomic gradient for all poisonings persisted over time, with higher rates among the more deprived (IRR 2.63, CI 2.41 to 2.88 for the most vs least deprived quintile in 2007-2012). CONCLUSIONS: Adolescent poisonings, especially intentional poisonings, have increased substantially over time and remain associated with health inequalities. Social and psychological support for adolescents should be targeted at more deprived communities, and child and adolescent mental health and alcohol support service provision should be commissioned to reflect the changing need.

BACKGROUND: Stroke is a leading cause of death and disability; worldwide it is estimated that 16.9 million people have a first stroke each year. Lipid-lowering, anticoagulant, and antihypertensive drugs can prevent strokes, but may be underused. METHODS AND FINDINGS: We analysed anonymised electronic primary care records from a United Kingdom (UK) primary care database that covers approximately 6% of the UK population. Patients with first-ever stroke/transient ischaemic attack (TIA), ≥18 y, with diagnosis between 1 January 2009 and 31 December 2013, were included. Drugs were considered under-prescribed when lipid-lowering, anticoagulant, or antihypertensive drugs were clinically indicated but were not prescribed prior to the time of stroke or TIA. The proportions of strokes or TIAs with prevention drugs under-prescribed, when clinically indicated, were calculated. In all, 29,043 stroke/TIA patients met the inclusion criteria; 17,680 had ≥1 prevention drug clinically indicated: 16,028 had lipid-lowering drugs indicated, 3,194 anticoagulant drugs, and 7,008 antihypertensive drugs. At least one prevention drug was not prescribed when clinically indicated in 54% (9,579/17,680) of stroke/TIA patients: 49% (7,836/16,028) were not prescribed lipid-lowering drugs, 52% (1,647/3,194) were not prescribed anticoagulant drugs, and 25% (1,740/7,008) were not prescribed antihypertensive drugs. The limitations of our study are that our definition of under-prescribing of drugs for stroke/TIA prevention did not address patients' adherence to medication or medication targets, such as blood pressure levels. CONCLUSIONS: In our study, over half of people eligible for lipid-lowering, anticoagulant, or antihypertensive drugs were not prescribed them prior to first stroke/TIA. We estimate that approximately 12,000 first strokes could potentially be prevented annually in the UK through optimal prescribing of these drugs. Improving prescription of lipid-lowering, anticoagulant, and antihypertensive drugs is important to reduce the incidence and burden of stroke and TIA.

PURPOSE: To provide expected incidence rates of Kawasaki disease after vaccination in routine clinical practice and as recommended within a pre-school National Immunisation Programme (NIP). METHODS: A post-immunisation risk period when Kawasaki disease onset might be associated with vaccination was defined as 28 days. Immunisation records for children under 6 years were identified from The Health Improvement Network (THIN) database of electronic UK primary health care records (2008-2012) and linked to previously validated cases of Kawasaki disease with an assigned date of onset. Kawasaki disease incidence in the risk period after a complete NIP recommended set of vaccinations was estimated for five vaccination stages individually and in total. RESULTS: A total of 642 170 complete pre-school immunisation stages from 275 986 children were included. Six cases of Kawasaki disease had onset in the risk period after any NIP stage providing an incidence of 12.8 per 100 000 person years (95%CI 5.7, 28.4). The incidence after any single immunisation stage ranged from 0 to 27.4 (95%CI 8.8, 84.8) per 100 000 person years. CONCLUSION: There were few cases of Kawasaki disease in the risk period after any NIP vaccination combination. The incidence rates will aid in the interpretation of clinical trials and post-marketing surveillance of new vaccines. Copyright © 2016 John Wiley & Sons, Ltd.

BACKGROUND: Antipsychotic (AP) drugs are commonly used to manage the behavioural symptoms of dementia. Nevertheless, international (i.e. the European Medicines Agency in Europe) and national (i.e. the Medicines and Healthcare products Regulatory Agency in the UK and the Italian Drug Agency) regulatory agencies issued safety warnings against AP use in dementia in 2004 and 2009. OBJECTIVE: The aim of this study is to investigate the short- and long-term impact of safety warnings on the use of APs in UK and Italian persons with dementia using two nationwide databases: The Health Improvement Network (THIN) from the UK and the Health Search Database-Cegedim-Strategic Data-Longitudinal Patient Database (HSD-CSD-LPD) from Italy. METHODS: We calculated the overall quarterly prevalence of AP use by class and by individual drug in persons with dementia aged ≥65 years and used generalized linear models to explore the effect of the safety warnings. RESULTS: We identified 58,497 and 10,857 individuals aged ≥65 years with dementia from the THIN and HSD-CSD-LPD databases, respectively, over the period 2000-2012. After the 2004 warnings, the use of atypical APs decreased, whereas the use of conventional APs increased, in Italy and the UK until 2009. However, the trend for APs individually showed that the use of risperidone/olanzapine decreased, whereas the use of quetiapine increased in both countries. After the 2009 warnings (until 2012), the use of atypical and conventional APs decreased in the UK (from 11 to 9 and 5 to 3 %, respectively), but such use increased in Italy (from 11 to 18 and 9 to 14 %, respectively). CONCLUSION: The 2004 warnings led to a reduction in the use of olanzapine and risperidone and increased the use of quetiapine/conventional APs in both countries. From 2009, the use of APs decreased in persons with dementia in the UK but not in Italy. Possible reasons for the difference in AP use between the two countries include a more proactive approach towards reducing the use of APs in the UK than in Italy.

OBJECTIVES: Estimate the effect of statin prescription on mortality in the population of England and Wales with no previous history of cardiovascular disease. METHODS: Primary care records from The Health Improvement Network 1987-2011 were used. Four cohorts of participants aged 60, 65, 70, or 75 years at baseline included 118,700, 199,574, 247,149, and 194,085 participants; and 1.4, 1.9, 1.8, and 1.1 million person-years of data, respectively. The exposure was any statin prescription at any time before the participant reached the baseline age (60, 65, 70 or 75) and the outcome was all-cause mortality at any age above the baseline age. The hazard of mortality associated with statin prescription was calculated by Cox's proportional hazard regressions, adjusted for sex, year of birth, socioeconomic status, diabetes, antihypertensive medication, hypercholesterolaemia, body mass index, smoking status, and general practice. Participants were grouped by QRISK2 baseline risk of a first cardiovascular event in the next ten years of <10%, 10-19%, or ≥20%. RESULTS: There was no reduction in all-cause mortality for statin prescription initiated in participants with a QRISK2 score <10% at any baseline age, or in participants aged 60 at baseline in any risk group. Mortality was lower in participants with a QRISK2 score ≥20% if statin prescription had been initiated by age 65 (adjusted hazard ratio (HR) 0.86 (0.79-0.94)), 70 (HR 0.83 (0.79-0.88)), or 75 (HR 0.82 (0.79-0.86)). Mortality reduction was uncertain with a QRISK2 score of 10-19%: the HR was 1.00 (0.91-1.11) for statin prescription by age 65, 0.89 (0.81-0.99) by age 70, or 0.79 (0.52-1.19) by age 75. CONCLUSIONS: The current internationally recommended thresholds for statin therapy for primary prevention of cardiovascular disease in routine practice may be too low and may lead to overtreatment of younger people and those at low risk.

BACKGROUND AND PURPOSE: Clinical management after transient ischaemic attack (TIA) is focused on stroke prevention; however, a number of small studies suggest that patients may experience ongoing residual impairments. METHODS: This was a retrospective matched-cohort study using anonymized electronic primary care records from The Health Improvement Network database, which covers approximately 6% of the UK population. Adults (≥ 18 years old) who experienced a first TIA between 2009 and 2013 were matched in a ratio of 1:5 to controls by age, sex and general practice. The time to first consultation for fatigue, psychological impairment or cognitive impairment was estimated by Kaplan-Meier survivor functions and adjusted hazard ratios. RESULTS: A total of 9419 TIA patients and 46 511 controls were included. The Kaplan-Meier curves showed that TIA patients were more likely than controls to consult for all three impairments (P < 0.0001). Within 7.1 months (95% confidence interval (CI), 6.2-8.2), 25% of TIA patients consulted for psychological impairment compared with 23.5 months (95% CI, 22.5-24.6) for controls. Hazard ratios for TIA patients were 1.43 (95% CI, 1.33-1.54) for consulting for fatigue, 1.26 (95% CI, 1.20-1.31) for psychological impairment and 1.45 (95% CI, 1.28-1.65) for cognitive impairment. CONCLUSIONS: Transient ischaemic attack is associated with significantly increased subsequent consultation for fatigue, psychological impairment and cognitive impairment. These findings suggest that impairments exist after initial symptoms of TIA have resolved, which should be considered by clinicians when treating TIA patients.

OBJECTIVES: although melatonin prescribing in England has been increasing in recent years, there have been no large scale studies on the safety of melatonin compared to other medical treatments for insomnia. The primary aim of this study was to examine the association between exposure to melatonin, hypnotic benzodiazepines (temazepam, nitrazepam) or Z-drugs (zolpidem, zopiclone) and fracture risk. DESIGN: retrospective cohort study. SETTING: 309 general practices contributing to The Health Improvement Network (THIN) between 2008 and 2013. PARTICIPANTS: 1,377 patients aged 45 years and older prescribed melatonin; 880 patients prescribed hypnotic benzodiazepines; 1,148 patients prescribed Z-drugs and 2,752 unexposed controls matched by age, gender and practice. MAIN OUTCOME: fracture following prescription of study drugs ascertained from practice records. RESULTS: the unadjusted hazard ratios for fracture during the follow-up period were 1.90 (95% CI 1.41-2.57) for melatonin, 1.70 (95% CI 1.18-2.46) for hypnotic benzodiazepines and 2.03 (95% CI 1.45-2.84) for Z-drugs. After adjustment for 26 covariates, the hazard ratios were 1.44 (95% CI 1.01-2.04) for melatonin, 1.26 (95% CI 0.82-1.92) for hypnotic benzodiazepines and 1.52 (95% CI 1.04-2.23) for Z-drugs. Only patients with three or more melatonin prescriptions had elevated risk. The mean time to fracture was 1.04 years and there was no significant difference in mean time to fracture between the cohorts. CONCLUSIONS: in this large cohort of patients attending UK primary care, prescriptions for melatonin and Z-drugs were associated with a significantly increased risk of fracture. With the use of melatonin increasing steadily overtime, this study adds to the literature on the safety profile of this drug.

BACKGROUND: Recent media reports have focused on the large increase in antidepressants dispensed in England. We investigated this, focusing on selective serotonin reuptake inhibitors (SSRIs). AIMS: To examine the rate of initiation of SSRIs over time and changes over time in the duration of prescribing episodes. METHOD: We estimated initiation and duration of SSRI prescribing from 7 025 802 individuals aged over 18 years and registered with a general practice that contributed data to The Health Improvement Network. RESULTS: Rates of SSRI initiation increased from 1.03 per 100 person-years in 1995 to 2.15 in 2001, but remained stable from then to 2012. The median duration of prescribing episodes increased from 112 to 169 days for episodes starting in 1995 to 2010. CONCLUSIONS: Despite media reports describing an increasing rate of antidepressant prescribing, SSRI initiation rates have stabilised since 2001. However, our results suggest that individuals who take SSRIs are receiving treatment for longer.

INTRODUCTION: Influenza vaccination through primary care has been recommended for all preschool children in the UK since 2013 as part of a universal immunisation programme. Vaccination is required annually and effectiveness varies by season. Factors associated with influenza vaccine receipt and those for other childhood vaccines may therefore differ. METHODS: We used The Health Improvement Network, a large primary care database, to create a cohort of children in England and Wales aged 2-4 years eligible for vaccination in the 2014/2015 season. Mixed-effects Poisson regression models were used to determine sociodemographic and clinical factors associated with influenza vaccine receipt, allowing for practice-level variation. RESULTS: Overall, 38.7% (95% CI 38.3% to 39.1%) of 57 545 children were vaccinated against influenza. Children in the poorest deprivation quintile were 19% less likely to receive influenza vaccine than those in the wealthiest quintile (adjusted risk ratio (ARR) 0.81, 95% CI 0.77 to 0.86). Children who received a timely first dose of measles-mumps-rubella vaccine were twice as likely to receive influenza vaccine (ARR 2.00 95% CI 1.87 to 2.13). Being 4 years old, not in a clinical risk group, or living with 2 or more other children were also significantly associated with a lower probability of vaccination. DISCUSSION: Children living in areas of higher deprivation and in larger families are less likely to receive influenza vaccine. Further research is required into whether interventions, such as offering vaccinations in other settings, could increase uptake in children, particularly in deprived areas.

BACKGROUND: Guidelines recommend limiting the duration of oral antibiotic therapy in acne to 3 to 6 months and prescribing concomitant topical retinoids for all patients. OBJECTIVE: We sought to evaluate the duration of therapy with oral tetracyclines and the use of topical retinoids among patients with acne treated primarily by general practitioners in the United Kingdom. METHODS: We conducted a retrospective cohort study using the Health Improvement Network database. RESULTS: The mean duration of therapy was 175.1 days. Of antibiotic courses, 62% were not associated with a topical retinoid; 29% exceeded 6 months in duration. If all regions were to achieve uses similar to the region with the shortest mean duration of therapy, approximately 3.3 million antibiotic days per year could be avoided in the United Kingdom. LIMITATIONS: The Health Improvement Network does not include information on acne severity and clinical outcomes. CONCLUSIONS: Prescribing behavior for oral antibiotics in the treatment of acne among general practitioners is not aligned with current guideline recommendations. Increasing the use of topical retinoids and considering alternative agents to oral antibiotics when appropriate represent opportunities to reduce antibiotic exposure and associated complications such as antibiotic resistance and to improve outcomes in patients treated for acne.