Publications
scientifiques

BACKGROUND: Herpes zoster (shingles) is a common viral disease increasing in risk and severity with age. Post-herpetic neuralgia (PHN), a complication of shingles, causes severe pain impacting quality of life (QoL). Zoster Vaccine Live (ZVL), a licensed vaccine for the prevention of shingles in the United Kingdom (UK), is part of the national immunisation programme (NIP) for adults aged 70-79. Public Health England (PHE) reports show shingles vaccine coverage varies, but is typically 50-60% across eligible cohorts. MATERIALS/METHODS: This retrospective, matched cohort study was conducted using The Health Improvement Network (THIN) UK primary care database. Individuals aged 70-79 were classified based on their vaccination status between September 2013 and May 2016. Risk and incidence rates for shingles were calculated for both groups over the duration of the study (mean 1.2 years). Vaccine effectiveness (VE) was calculated using the equation 1-relative risk (RR) for shingles and PHN. RESULTS: Within the total cohort (n = 295,135), 70,867 (24%) were vaccinated and 224,268 (76%) were unvaccinated. 2435 (0.83%) patients developed shingles: 241 (0.34%) among the vaccinated and 2194 (0.98%) among the unvaccinated. The VE for preventing shingles was 65.3% (95% CI: 60.3-69.6%). The incidence rate in the vaccinated group was 2.95 (95% CI: 2.59-3.34) vs 8.02 (95% CI: 7.68-8.36) per 1000 person years in the unvaccinated group. Risk of PHN was 0.02% and 0.06% in the respective vaccinated and unvaccinated groups. The VE for preventing PHN was 72% (95% CI: 50.0-83.9%). PHN incidence rates were 0.16 (95% CI: 0.08-0.27) and 0.53 (95% CI: 0.44-0.62) per 1000 person years in the vaccinated and unvaccinated groups, respectively. CONCLUSIONS: ZVL reduced the risk of shingles among an elderly population. Given the negative impact of shingles and PHN on QoL, the benefits of vaccination are clear. Improving uptake in the UK is needed in this population.

Background Aspirin is of uncertain benefit for primary prevention in patients with type 2 diabetes mellitus (T2D). We assessed whether primary prevention with aspirin is beneficial in patients with T2D and heart failure ( HF ). Methods and Results Data from The Health Improvement Network, a UK multicenter prospective primary care database, were analyzed. Those with T2D and HF , age ≥55 years, and no previous history of myocardial infarction and/or coronary artery disease, stroke, peripheral artery disease, or atrial fibrillation were included. We compared outcomes for those on aspirin to no aspirin after diagnosis of HF and T2D and assessed the role of a >75-mg dose. The primary outcome was a composite of all-cause mortality and hospitalization for HF ; secondary outcomes were nonfatal stroke, nonfatal myocardial infarction, or major bleeding. There were 5967 participants on aspirin and 6567 not on aspirin. The mean age ( SD ) was 75.3 (9.6) years, 53.9% were men, and the mean follow-up ( SD ) was for 5 (4.2) years. After propensity-score matching and further multivariable adjustment, aspirin was significantly associated with a decrease in the primary outcome and all-cause mortality (hazard ratio=0.88, 95% confidence interval 0.82-0.93; 0.88, 0.83-0.94], respectively); and an increased risk of nonfatal myocardial infarction (hazard ratio=1.66; 95% confidence interval 1.49-1.85) and nonfatal stroke (hazard ratio=1.23, 1.01-1.50). Major bleedings and hospitalization for HF were not significantly higher with aspirin (hazard ratio=0.68, 0.45-1.03; 0.87, 0.66-1.15, respectively). There was no additional benefit for a dose >75 mg. Conclusions Primary prevention with aspirin in patients with T2D and HF is associated with lower all-cause mortality.

OBJECTIVES: To compare the rate, indications and type of antibiotic prescriptions in children with and without asthma. DESIGN: A retrospective cohort study. SETTING: Two population-based primary care databases: Integrated Primary Care Information database (IPCI; the Netherlands) and The Health Improvement Network (THIN; the UK). PARTICIPANTS: Children aged 5-18 years were included from January 2000 to December 2014. A child was categorised as having asthma if there were ≥2 prescriptions of respiratory drugs in the year following a code for asthma. Children were labelled as non-asthmatic if no asthma code was recorded in the patient file. MAIN OUTCOME MEASURES: Rate of antibiotic prescriptions, related indications and type of antibiotic drugs. RESULTS: The cohorts in IPCI and THIN consisted of 946 143 and 7 241 271 person years (PY), respectively. In both cohorts, antibiotic use was significantly higher in asthmatic children (IPCI: 197vs126 users/1000 PY, THIN: 374vs250 users/1000 PY). In children with asthma, part of antibiotic prescriptions were for an asthma exacerbation only (IPCI: 14%, THIN: 4%) and prescriptions were more often due to lower respiratory tract infections then in non-asthmatic children (IPCI: 18%vs13%, THIN: 21%vs12%). Drug type and quality indicators depended more on age, gender and database than on asthma status. CONCLUSIONS: Use of antibiotics was higher in asthmatic children compared with non-asthmatic children. This was mostly due to diseases for which antibiotics are normally not indicated according to guidelines. Further awareness among physicians and patients is needed to minimise antibiotic overuse and limit antibiotic resistance.

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BACKGROUND: Follow-up studies of weight gain related to antipsychotic treatment beyond a year are limited in number. We compared weight change in the three most commonly prescribed antipsychotics in a representative UK General Practice database. METHOD: We conducted a cohort study in United Kingdom primary care records of people newly prescribed olanzapine, quetiapine or risperidone. The primary outcome was weight in each six month period for two years after treatment initiation. Weight changes were compared using linear regression, adjusted for age, baseline weight and diagnosis. RESULTS: N = 6338 people received olanzapine, 12,984 quetiapine and 6556 risperidone. Baseline weight was lowest for men treated with olanzapine (80.8 kg versus 83.5 kg quetiapine, 82.0 kg risperidone) and women treated with olanzapine (67.7 kg versus 71.5 kg quetiapine 68.4 kg risperidone. Weight gain occurred during treatment with all three drugs. Compared with risperidone mean weight gain was higher with olanzapine (adjusted co-efficient +1.24 kg (95% confidence interval: 0.69-1.79 kg per six months) for men and +0.77 kg (95% confidence interval: 0.29-1.24 kg) for women). Weight gain with quetiapine was lower in unadjusted models compared with risperidone, but this difference was not significant after adjustment. CONCLUSION: Olanzapine is more commonly prescribed to people with lower weight. However, after accounting for baseline weight, age, sex and diagnosis, olanzapine is still associated with greater weight gain over two years than risperidone or quetiapine. Baseline weight does not ameliorate the risks of weight gain associated with antipsychotic medication. Weight gain should be assertively discussed and managed for people prescribed antipsychotics, especially olanzapine.

PURPOSE: Identification of hospitalizations for infection is important for post-marketing surveillance of drugs, but the validity of using diagnosis codes to identify these events is unknown. Differentiating between hospitalization for and with infection is important, as the latter is common and less likely to arise from pre-admission exposure to drugs. We determined positive predictive values (PPVs) of diagnostic coding-based algorithms to identify hospitalization for infection among patients prescribed oral anti-diabetic drugs (OADs). METHODS: We identified patients initiating OADs within 2 United States claims databases (Medicare, HealthCore Integrated Research Database [HIRD ]) and 2 United Kingdom electronic medical record databases (Clinical Practice Research Datalink [CPRD], The Health Improvement Network [THIN]) from 2009 to 2014. To identify potential hospitalizations for infection, we selected patients with a hospital diagnosis of infection and, within 7 days prior to hospitalization, either an outpatient/emergency department visit with an infection diagnosis or outpatient antimicrobial treatment. Hospital records were reviewed by infectious disease specialists to adjudicate hospital admissions for infection. PPVs for confirmed outcomes were determined for each database. RESULTS: Code-based algorithms to identify hospitalization for infection had PPVs exceeding 80% within Medicare (PPV, 83% [90/109]; 95% CI, 74-89%), HIRD (PPV, 89% [73/82]; 95% CI, 80-95%), and THIN (PPV, 86% [12/14]; 95% CI, 57-98%) but not within CPRD (PPV, 67% [14/21]; 95% CI, 43-85%). CONCLUSIONS: Algorithms identifying hospitalization for infection utilizing hospital diagnoses along with antecedent outpatient/emergency infection diagnoses or antimicrobial therapy had sufficiently high PPVs for confirmed events within Medicare, HIRD , and THIN to enable their use for pharmacoepidemiologic research.

BACKGROUND: The use of medications to treat attention deficit hyperactivity disorder (ADHD) has increased, but the prevalence of ADHD medication use across different world regions is not known. Our objective was to determine regional and national prevalences of ADHD medication use in children and adults, with a specific focus on time trends in ADHD medication prevalence. METHODS: We did a retrospective, observational study using population-based databases from 13 countries and one Special Administrative Region (SAR): four in Asia and Australia, two in North America, five in northern Europe, and three in western Europe. We used a common protocol approach to define study populations and parameters similarly across countries and the SAR. Study populations consisted of all individuals aged 3 years or older between Jan 1, 2001, and Dec 31, 2015 (dependent on data availability). We estimated annual prevalence of ADHD medication use with 95% CI during the study period, by country and region and stratified by age and sex. We reported annual absolute and relative percentage changes to describe time trends. FINDINGS: 154·5 million individuals were included in the study. ADHD medication use prevalence in 2010 (in children aged 3-18 years) varied between 0·27% and 6·69% in the countries and SAR assessed (0·95% in Asia and Australia, 4·48% in North America, 1·95% in northern Europe, and 0·70% in western Europe). The prevalence of ADHD medication use among children increased over time in all countries and regions, and the absolute increase per year ranged from 0·02% to 0·26%. Among adults aged 19 years or older, the prevalence of any ADHD medication use in 2010 varied between 0·003% and 1·48% (0·05% in Asia and Australia, 1·42% in North America, 0·47% in northern Europe, and 0·03% in western Europe). The absolute increase in ADHD medication use prevalence per year ranged from 0·0006% to 0·12%. Methylphenidate was the most commonly used ADHD medication in most countries. INTERPRETATION: Using a common protocol and data from 13 countries and one SAR, these results show increases over time but large variations in ADHD medication use in multiple regions. The recommendations of evidence-based guidelines need to be followed consistently in clinical practice. Further research is warranted to describe the safety and effectiveness of ADHD medication in the short and long term, and to inform evidence-based guidelines, particularly in adults. FUNDING: None.

AIMS: To determine the risk of venous thromboembolism (VTE) defined as the combined endpoint of deep venous thrombosis (DVT) and pulmonary embolism (PE) among patients with psoriatic arthritis (PsA), psoriasis and rheumatoid arthritis (RA) compared with population controls. METHODS AND RESULTS: A cohort study was conducted in a primary care medical record database in the UK with data from 1994-2014 among patients with PsA, RA, or psoriasis. Cox proportional hazards models were used to calculate the relative hazards for DVT, PE, and VTE. An interaction with disease modifying anti-rheumatic drugs (DMARD) was hypothesized a priori and was significant. Patients with PsA (n = 12 084), RA (n = 51 762), psoriasis (n = 194 288) and controls (n = 1 225 571) matched on general practice and start date were identified. Patients with RA (with and without a DMARD prescription) and patients with mild psoriasis had significantly elevated risks of VTE (HR 1.35, 1.29, and 1.07, respectively) after adjusting for traditional risk factors. Severe psoriasis and PsA prescribed a DMARD had an elevated but not statistically significant risk for VTE. Findings were similar for DVT. The age-and-sex-adjusted risk of PE was elevated in RA, severe psoriasis and PsA patients prescribed a DMARD. CONCLUSION: While systemic inflammation is a risk factor for VTE, the risk of VTE compared with controls is different among patients with three different inflammatory disorders: RA, PsA, and psoriasis.

BACKGROUND AND OBJECTIVES: In the USA the benefit-risk profile of fluoroquinolones for treating patients with acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, and uncomplicated urinary tract infections (uUTIs) is considered unfavorable. However, the number of fluoroquinolone products in the EU indicated and prescribed for these infections is uncertain. The objective of this study was to provide data on indications for fluoroquinolones in Europe and examine the prevalence of prescribing in France, Germany and the UK. METHODS: Descriptive analysis of indications for systemic fluoroquinolone antibiotics across the European Economic Area (EEA) and descriptive analysis of systemic fluoroquinolone antibiotic prescribing in France, Germany and UK electronic health records (2000-2015). RESULTS: All EEA countries had fluoroquinolone products indicated for acute sinusitis, acute bronchitis, or uUTIs, with differences in the number of products between countries for: acute sinusitis (19.5-51.9%), acute bronchitis (22.2-73.4%), and uUTIs (52.0-89.1%). The prevalence of fluoroquinolone prescribing for the treatment of respiratory tract infections (RTIs) appeared to fall with time in all countries and for UTI in France and UK only. Changes were greatest in the UK. In France, Germany, and the UK, respectively: acute sinusitis accounted for 29.5, 20.6, and 40.7% of all oral fluoroquinolone prescriptions for upper RTIs; acute bronchitis accounted for 63.0, 83.0, and 89.9% of all fluoroquinolone prescriptions for lower RTIs; uUTIs accounted for 83.3, 89.9, and 32.2% of all fluoroquinolone prescriptions for UTIs. CONCLUSION: Large numbers of fluoroquinolone products in Europe are listed for the treatment of milder infections such as acute bronchitis, acute sinusitis and uUTIs. Among the countries assessed, fluoroquinolones were commonly prescribed for these conditions and potentially should lead to a review of therapeutic guidelines.

OBJECTIVES: To investigate how depression is recognised in the year after child birth and treatment given in clinical practice. DESIGN: Cohort study based on UK primary care electronic health records. SETTING: Primary care. PARTICIPANTS: Women who have given live birth between 2000 and 2013. OUTCOMES: Prevalence of postnatal depression, depression diagnoses, depressive symptoms, antidepressant and non-pharmacological treatment within a year after birth. RESULTS: Of 206 517 women, 23 623 (11%) had a record of depressive diagnosis or symptoms in the year after delivery and more than one in eight women received antidepressant treatment. Recording and treatment peaked 6-8 weeks after delivery. Initiation of selective serotonin reuptake inhibitors (SSRI) treatment has become earlier in the more recent years. Thus, the initiation rate of SSRI treatment per 100 pregnancies (95% CI) at 8 weeks were 2.6 (2.5 to 2.8) in 2000-2004, increasing to 3.0 (2.9 to 3.1) in 2005-2009 and 3.8 (3.6 to 3.9) in 2010-2013. The overall rate of initiation of SSRI within the year after delivery, however, has not changed noticeably. A third of the women had at least one record suggestive of depression at any time prior to delivery and of these one in four received SSRI treatment in the year after delivery.Younger women were most likely to have records of depression and depressive symptoms. (Relative risk for postnatal depression: age 15-19: 1.92 (1.76 to 2.10), age 20-24: 1.49 (1.39 to 1.59) versus age 30-34). The risk of depression, postnatal depression and depressive symptoms increased with increasing social deprivation. CONCLUSIONS: More than 1 in 10 women had electronic health records indicating depression diagnoses or depressive symptoms within a year after delivery and more than one in eight women received antidepressant treatment in this period. Women aged below 30 and from the most deprived areas were at highest risk of depression and most likely to receive antidepressant treatment.

INTRODUCTION: Intrauterine devices are implantable contraceptives of which some brands steadily release levonorgestrel over an extended time period. Exposure to a levonorgestrel-releasing intrauterine device has been associated with depression and, more recently, a connection to anxiety, panic attacks, sleep problems and restlessness has been suggested. This study uses data from the THIN database of UK general practice to investigate these suggestions. METHODS: A cohort study was performed to compare the incidence of psychiatric adverse events between groups of women who were new users of levonorgestrel-releasing and non-hormonal intrauterine devices. Hazard ratios for the first occurrence of psychiatric symptoms or prescriptions of disease-specific treatments were calculated on an intention-to-treat basis using a proportional hazards model. RESULTS: Significant associations were found between levonorgestrel exposure and records of anxiety (hazard ratio = 1.18; 95% confidence interval 1.08-1.29) and sleep problems (hazard ratio = 1.22; 95% confidence interval 1.08-1.38) in women without a prior record of these events. No significant associations were found for panic attacks or restlessness. Clear baseline differences in clinical characteristics and age between the groups were present. These were included in the model as potential confounding factors. CONCLUSION: Statistically significant associations of levonorgestrel exposure with anxiety and sleep problems were observed. Substantive differences in baseline characteristics of the treated groups make robust conclusions difficult but the results strongly suggest that additional studies are warranted.