Scientific
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BACKGROUND: Activation of the immune system has been demonstrated in atopy and functional gastrointestinal disorders (FGIDs). Previous data from our group have suggested a connection between immune dysregulation, FGIDs and mood disorders. AIM: To investigate if these data translate to clinical practice and examine connections from the perspective of FGIDs to determine whether atopy and FGIDs are connected via mood disorders. METHODS: Evidence of irritable bowel syndrome (IBS), functional dyspepsia (FD) and constipation was sought from the medical records of 30,000 primary care records over a minimum 5 year period. The same records yielded diagnoses of four atopic conditions (asthma, eczema, allergic rhinitis/hay fever and conjunctivitis). RESULTS: Atopic conditions were found in excess among all FGID groups considered when compared with controls. In the groups with IBS alone (OR = 1.43, 1.29-1.58), FD alone (OR = 1.41, 1.26-1.58) and those with multiple FGIDs (OR = 1.92, 1.75-2.12) there was elevated prevalence of asthma compared with controls without a FGID. Across disorders the excess was generally highest among patients diagnosed with multiple FGIDs (rhinitis/hay fever OR = 3.74, 3.32-4.20; conjunctivitis OR = 3.00, 2.49-3.62) and was only partly explained by a common association between both FGIDs and atopic conditions with mood disorders, although not for every atopic/FGID combination (rhinitis/hay fever OR = 2.60, 2.29-2.96, conjunctivitis OR = 2.34, 1.90-2.87). CONCLUSIONS: Irritable bowel syndrome, functional dyspepsia and constipation share an association with atopy that is only partly explained via a common connection with mood disorders. These data have important implications for understanding both the pathophysiology of functional gastrointestinal disorders and development of new treatments.

BACKGROUND: Around ten percent of the population have been reported as having Chronic Kidney Disease (CKD), which is associated with increased cardiovascular mortality. Few previous studies have ascertained the chronicity of CKD. In the UK, a payment for performance (P4P) initiative incentivizes CKD (stages 3-5) recognition and management in primary care, but the impact of this has not been assessed. METHODS AND FINDINGS: Using data from 426 primary care practices (population 2,707,130), the age standardised prevalence of stages 3-5 CKD was identified using two consecutive estimated Glomerular Filtration Rates (eGFRs) seven days apart. Additionally the accuracy of practice CKD registers and the relationship between accurate identification of CKD and the achievement of P4P indicators was determined. Between 2005 and 2009, the prevalence of stages 3-5 CKD increased from 0.3% to 3.9%. In 2009, 30,440 patients (1.1% unadjusted) fulfilled biochemical criteria for CKD but were not on a practice CKD register (uncoded CKD) and 60,705 patients (2.2% unadjusted) were included on a practice CKD register but did not fulfil biochemical criteria (miscoded CKD). For patients with confirmed CKD, inclusion in a practice register was associated with increasing age, male sex, diabetes, hypertension, cardiovascular disease and increasing CKD stage (p<0.0001). Uncoded CKD patients compared to miscoded patients were less likely to achieve performance indicators for blood pressure (OR 0.84, 95% CI 0.82-0.86 p<0.001) or recorded albumin-creatinine ratio (OR 0.73, 0.70-0.76, p<0.001). CONCLUSIONS: The prevalence of stages 3-5 CKD, using two laboratory reported eGFRs, was lower than estimates from previous studies. Clinically significant discrepancies were identified between biochemically defined CKD and appearance on practice registers, with misclassification associated with sub-optimal care for some people with CKD.

In this retrospective database study, carried out using The Health Improvement Network, a UK primary care database, we followed up patients who were prescribed low-dose acetylsalicylic acid (ASA) (75-300 mg/day) for the secondary prevention of cardiovascular disease in 2000-2007, and who discontinued therapy for a period of at least 90 days during that time (n = 11,565). We assessed the incidence of, and factors associated with, ASA represcription. Patients were followed up from the first day after their initial 90-day period of discontinuation (start date) until ASA represcription, death, or the end of the study period (31 December 2010). Hazard ratios for factors associated with represcription were calculated using Cox regression models. The cumulative incidence of ASA represcription was 85.2% over the entire follow-up period, and 63.5% of all represcriptions were received in the first 6 months after patients' start dates. Factors significantly associated with a reduced likelihood of ASA represcription included being aged 75-84 years, cardiovascular and gastrointestinal comorbidities (in particular, atrial fibrillation and high overall gastrointestinal risk), adverse drug reactions experienced during therapy, and use of gastroprotective or cardiovascular medications (most notably warfarin). Factors significantly associated with an increased likelihood of ASA represcription included obesity, diabetes mellitus, stable angina, depression, and use of non-steroidal anti-inflammatory drugs. In conclusion, approximately 85% of patients who discontinued low-dose ASA therapy were subsequently represcribed ASA during the study period. Comorbidities and comedication use affected represcription rates.

AIMS/HYPOTHESIS: The aim of this work was to study levels of HbA1c and patterns of adjusting glucose-lowering drugs in patients with impaired glycaemic control over 10 years after diagnosis of type 2 diabetes. METHODS: We studied 4,529 individuals in The Health Improvement Network Database newly diagnosed with type 2 diabetes in the year 2000. RESULTS: From 6 months to 10 years after diagnosis, the HbA1c increased from 7.04% (53.4 mmol/mol) to 7.49% (58.3 mmol/mol) (average annual change: 0.047% [0.51 mmol/mol]). The greatest annual change occurred between 6 months and 2 years (0.21% [2.30 mmol/mol] increase per year, p < 0.001), followed by the 2-5 year time period (0.033% [0.36 mmol/mol] increase per year, p < 0.001). No significant increase in HbA1c occurred between 5 and 10 years (p = 0.20). In multivariable analyses, patients who were younger (p < 0.001), with higher BMI (p = 0.033) and who were current insulin users (p = 0.024) at diagnosis had greater increases in HbA1c between 6 months and 2 years. For individuals with HbA1c above 7.0% (53 mmol/mol) the mean time to next measurement of HbA1c was 0.53 years and increase in doses or changes to other glucose-lowering medications were performed in 26% of cases. CONCLUSIONS/INTERPRETATION: HbA1c increases by approximately 0.5% (5 mmol/mol) over 10 years after diagnosis of type 2 diabetes, with the main increase appearing in the first years after diagnosis. More frequent monitoring of HbA1c and adjustments of glucose-lowering drugs may be essential to prevent the decline.

BACKGROUND: Since the introduction of the Quality and Outcomes framework, there has been some evidence of improvement in the management of chronic obstructive pulmonary disease (COPD) patients in the United Kingdom through increasing rates of smoking cessation advice and immunisations against influenza. However, it is unknown whether disease-specific management criteria, disease outcomes and diagnosis have improved. AIMS: To describe changes in the management and outcomes of patients with COPD in UK general practice between 2000 and 2009. METHODS: The study was done on a retrospective cohort using data from The Health Improvement Network UK primary care database. We calculated age at diagnosis of COPD and death, total number of short-term oral corticosteroid courses and consultations, and proportion of patients with very severe COPD and on triple inhaled therapy for each year between 2000 and 2009. RESULTS: We identified 92,576 patients with COPD. The mean age at COPD diagnosis decreased from 68.1 years in 2000 to 66.7 years in 2009. The mean age at death increased from 78.2 years in 2000 to 78.8 years in 2009. The number of prescribed courses of oral corticosteroids increased from 0.6 in 2000 to 0.8 in 2009. The number of consultations increased from 9.4 in 2004 to 11.3 in 2009. The risk of having very severe COPD decreased from 9.4% in 2004 to 6.8% in 2009. The likelihood of patients with very severe COPD receiving triple therapy increased from 25% in 2004 to 59% in 2009. CONCLUSIONS: The trends suggest that management and outcomes observed in patients with COPD may have improved since the year 2000.

BACKGROUND: To describe the utilisation of antibiotics in children and adolescents across 5 European countries based on the same drug utilisation measures and age groups. Special attention was given to age-group-specific distributions of antibiotic subgroups, since comparison in this regard between countries is lacking so far. METHODS: Outpatient paediatric prescriptions of systemic antibiotics during the years 2005-2008 were analysed using health care databases from the UK, the Netherlands, Denmark, Italy and Germany. Annual antibiotic prescription rates per 1,000 person years were estimated for each database and stratified by age (≤4, 5-9, 10-14, 15-18 years). Age-group-specific distributions of antibiotic subgroups were calculated for 2008. RESULTS: With 957 prescriptions per 1000 person years, the highest annual prescription rate in the year 2008 was found in the Italian region Emilia Romagna followed by Germany (561), the UK (555), Denmark (481) and the Netherlands (294). Seasonal peaks during winter months were most pronounced in countries with high utilisation. Age-group-specific use varied substantially between countries with regard to total prescribing and distributions of antibiotic subgroups. However, prescription rates were highest among children in the age group ≤4 years in all countries, predominantly due to high use of broad spectrum penicillins. CONCLUSIONS: Strong increases of antibiotic prescriptions in winter months in high utilising countries most likely result from frequent antibiotic treatment of mostly viral infections. This and strong variations of overall and age-group-specific distributions of antibiotic subgroups across countries, suggests that antibiotics are inappropriately used to a large extent.

PURPOSE: The aim of this study is to determine if oral fluoroquinolone exposure is associated with an increased hazard for having a retinal tear or detachment. METHODS: A retrospective cohort study was performed using individuals who met inclusion criteria from The Health Improvement Network database. Cohorts were created for individuals who had a prescription written for either an oral fluoroquinolone or an oral β-lactam antibiotic (comparison group). Subjects were excluded if they had a previous diagnosis of a retinal tear or detachment (hereafter retinal break (RB)), or a procedure code to treat an RB, where in the practice for less than 365 days, had a previous prescription for either antibiotic within 365 days of the index date or had intraocular surgery or a diagnosis of endophthalmitis within 90 days prior to the antibiotic prescription. Covariates of interest were age, gender, diabetes, and year of index. The primary outcome measure of interest was the hazard ratio (HR) of undergoing a procedure to treat an RB within 7, 30, 90, or 365 days after exposure to an oral fluoroquinolone prescription versus an oral β-lactam prescription. RESULTS: After exclusions, 6,604,423 prescriptions (290,393 fluoroquinolone; 6,314,030 β-lactam) from 3,413,498 patients (247,073 fluoroquinolone; 3,303,641 β-lactam) and 2685 RB procedures were eligible for analysis (661 retinal tears and 2024 retinal detachments). For fluoroquinolones, 0, 1, 5, and 23 RBs occurred at the 7-, 30-, 90-, and 365-day time points, respectively. For β-lactam prescriptions, 7, 28, 87, and 373 RBs occurred at the 7-, 30-, 90-, and 365-day time points, respectively. Because of zero events occurring in the fluoroquinolone cohort during the 7-day observation period, an unadjusted or an adjusted HR (and subsequent p-value or confidence intervals) was unable to be calculated. Univariate and multivariate analyses demonstrated that fluoroquinolones were not significantly associated with RB in the 30-, 90-, or 365-day observation periods (30-day HR = 0.78, p = 0.80, 95%CI: 0.11, 5.71; 90-day HR = 1.25, p = 0.63, 95%CI: 0.51, 3.08; and 365-day HR = 1.35, p = 0.16, 95%CI: 0.89, 2.06). CONCLUSIONS: Our results do not support an association between oral fluoroquinolone use and subsequent procedures to treat an RB.

BACKGROUND: Few epidemiologic studies have investigated predictors of uncomplicated peptic ulcer disease (PUD) separately from predictors of complicated PUD. OBJECTIVE: To analyze risk factors associated with uncomplicated PUD and medication use after diagnosis. METHODS: Patients diagnosed with uncomplicated PUD (n = 3,914) were identified from The Health Improvement Network database among individuals aged 40-84 years during 1997-2005, with no previous history of PUD. Prescription records for the year after the date of diagnosis were reviewed and a nested case-control analysis was performed to calculate the odds ratios for the association of potential risk factors with PUD. RESULTS: Medications associated with developing uncomplicated PUD included current use of acetylsalicylic acid (ASA), nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol, selective serotonin reuptake inhibitors, antidepressants, antihypertensives or acid suppressants. Uncomplicated PUD was significantly associated with being a current or former smoker and having had a score of at least 3 on the Townsend deprivation index. Approximately 50% of patients who were users of ASA (19% of patients) or chronic users of NSAIDs (7% of patients) at diagnosis did not receive another prescription of the medication in the 60 days after diagnosis, and 30% were not represcribed therapy within a year. Among patients who were current users of ASA or chronic NSAIDs at the time of the PUD diagnosis and received a subsequent prescription for their ASA or NSAID during the following year, the vast majority (80-90%) also received a proton pump inhibitor coprescription. CONCLUSIONS: Our results indicate that several risk factors for upper gastrointestinal bleeding are also predictors of uncomplicated PUD, and that some patients do not restart therapy with ASA or NSAIDs after a diagnosis of uncomplicated PUD. Further investigation is needed regarding the consequences for these patients in terms of increased cardiovascular burden due to discontinuation of antiplatelet therapy.

OBJECTIVE: Previous studies evaluating the effect of metformin on cancer risk have been impacted by time-related biases. To avoid these biases, we examined the incidence of bladder cancer in new users of metformin and sulfonylureas (SUs). RESEARCH DESIGN AND METHODS: This cohort study included 87,600 patients with type 2 diabetes in The Health Improvement Network database. Use of metformin or an SU was treated as a time-dependent variable. Cox regression-generated hazard ratios (HRs) compared metformin use with SU use, adjusted for age, sex, smoking, obesity, and HbA1c level. RESULTS: We identified 196 incident bladder cancers in the metformin cohort and 66 cancers in the SU cohort. Use of metformin was not associated with decreased bladder cancer risk (HR 0.81 [95% CI 0.60-1.09]). This association did not differ by sex (P for interaction = 0.20). We observed no association with duration of metformin relative to SU use (3 to <4 years of use: 0.57 [0.25-1.34]; 4 to <5 years of use: 0.93 [0.30-2.85; ≥5 years of use: 1.18 [0.44-3.19]; P for trend = 0.26). CONCLUSIONS: Use of metformin is not associated with a decreased incidence of bladder cancer. Similar methods should be used to study other cancers that have previously been identified as potentially preventable with metformin.

OBJECTIVES: Stroke and TIA are recognized complications of acute herpes zoster (HZ). Herein, we evaluate HZ as a risk factor for cerebrovascular disease (stroke and TIA) and myocardial infarction (MI) in a UK population cohort. METHODS: A retrospective cohort of 106,601 HZ cases and 213,202 controls, matched for age, sex, and general practice, was identified from the THIN (The Health Improvement Network) general practice database. Cox proportional hazard models were used to examine the risks of stroke, TIA, and MI in cases and controls, adjusted for vascular risk factors, including body mass index >30 kg/m(2), smoking, cholesterol >6.2 mmol/L, hypertension, diabetes, ischemic heart disease, atrial fibrillation, intermittent arterial claudication, carotid stenosis, and valvular heart disease, over 24 (median 6.3) years after HZ infection. RESULTS: Risk factors for vascular disease were significantly increased in cases of HZ compared with controls. Adjusted hazard ratios for TIA and MI but not stroke were increased in all patients with HZ (adjusted hazard ratios [95% confidence intervals]: 1.15 [1.09-1.21] and 1.10 [1.05-1.16], respectively). However, stroke, TIA, and MI were increased in cases whose HZ occurred when they were younger than 40 years (adjusted hazard ratios [95% confidence intervals]: 1.74 [1.13-2.66], 2.42 [1.34-4.36], and 1.49 [1.04-2.15], respectively). Subjects younger than 40 years were significantly less likely to be asked about vascular risk factors compared with older patients (p < 0.001). CONCLUSION: HZ is an independent risk factor for vascular disease in the UK population, particularly for stroke, TIA, and MI in subjects affected before the age of 40 years. In older subjects, better ascertainment of vascular risk factors and earlier intervention may explain the reduction in risk of stroke after HZ infection.

OBJECTIVE: To explore whether there are gender differences in the number of GP recorded cases, the probability of survival and consulting pattern prior to diagnosis amongst patients with three non-sex-specific cancers. DESIGN: Cross sectional study. SETTING: UK primary care. SUBJECTS: 12,189 patients aged 16 years or over diagnosed with colorectal cancer (CRC), 11,081 patients with lung cancer and 4,352 patients with malignant melanoma, with first record of cancer diagnosis during 1997-2006. MAIN OUTCOME MEASURES: Cancer cases recorded in primary care; probability of survival following diagnosis; and number of GP contacts within the 24 months preceding diagnosis. RESULTS: From 1997-2006, overall rates of GP recorded CRC and lung cancer cases recorded were higher in men than in women, but rates of malignant melanoma were higher in women than in men. Gender differences in survival were small; 49% of men and 53% of women survived at least 5 years following CRC diagnosis; 9% of men and 12% of women with lung cancer, and 77% of men and 86% of women with malignant melanoma. The adjusted male to female relative hazard ratio of death in all patients was 1.20 (95%CI 1.13-1.30), 1.24 (95%CI 1.16-1.33) and 1.73 (95%CI 1.51-2.00) for CRC, lung cancer and malignant melanoma respectively. However, gender differences in the relative risk were much smaller amongst those who died during follow-up. For each cancer, there was little evidence of gender difference in the percentage who consulted and the number of GP contacts made within 24 months prior to diagnosis. CONCLUSIONS: This study found that patterns of consulting prior to cancer diagnosis differed little between two genders, providing no support for the hypothesis that gender differences in survival are explained by gender differences in consultation for more serious illness, and suggests the need for a more critical view of gender and consultation.

OBJECTIVES: To determine to what extent underlying data published as part of Quality and Outcomes Framework (QOF) can be used to estimate smoking prevalence within practice populations and local areas and to explore the usefulness of these estimates. DESIGN: Cross-sectional, observational study of QOF smoking data. Smoking prevalence in general practice populations and among patients with chronic conditions was estimated by simple manipulation of QOF indicator data. Agreement between estimates from the integrated household survey (IHS) and aggregated QOF-based estimates was calculated. The impact of including smoking estimates in negative binomial regression models of counts of premature coronary heart disease (CHD) deaths was assessed. SETTING: Primary care in the East Midlands. PARTICIPANTS: All general practices in the area of study were eligible for inclusion (230). 14 practices were excluded due to incomplete QOF data for the period of study (2006/2007-2012/2013). One practice was excluded as it served a restricted practice list. MEASUREMENTS: Estimates of smoking prevalence in general practice populations and among patients with chronic conditions. RESULTS: Median smoking prevalence in the practice populations for 2012/2013 was 19.2% (range 5.8-43.0%). There was good agreement (mean difference: 0.39%; 95% limits of agreement (-3.77, 4.55)) between IHS estimates for local authority districts and aggregated QOF register estimates. Smoking prevalence estimates in those with chronic conditions were lower than for the general population (mean difference -3.05%), but strongly correlated (Rp=0.74, p<0.0001). An important positive association between premature CHD mortality and smoking prevalence was shown when smoking prevalence was added to other population and service characteristics. CONCLUSIONS: Published QOF data allow useful estimation of smoking prevalence within practice populations and in those with chronic conditions; the latter estimates may sometimes be useful in place of the former. It may also provide useful estimates of smoking prevalence in local areas by aggregating practice based data.

PURPOSE: Drug utilization studies have applied different methods to various data types to describe medication use, which hampers comparisons across populations. The aim of this study was to describe the time trends in antidepressant prescribing in the last decade and the variation in the prevalence, calculated in a uniform manner, in seven European electronic healthcare databases. METHODS: Annual prevalence per 10,000 person-years (PYs) was calculated for 2001-2009 in databases from Spain, Germany, Denmark, the United Kingdom (UK), and the Netherlands. Prevalence data were stratified according to age, sex, antidepressant type (selective serotonin re-uptake inhibitors [SSRIs] or tricyclic antidepressants [TCAs]) and major indications. RESULTS: The age- and sex-standardized prevalence was lowest in the two Dutch (391 and 429 users per 10,000 PYs) and highest in the two UK (913 and 936 users per 10,000 PYs) populations in 2008. The prevalence in the Danish, German, and Spanish populations was 637, 618, and 644 users per 10,000 PY respectively. Antidepressants were prescribed most often in 20- to 60-year-olds in the two UK populations compared with the others. SSRIs were prescribed more often than TCAs in all except the German population. In the majority of countries we observed an increasing trend of antidepressant prescribing over time. Two different methods identifying recorded indications yielded different ranges of proportions of patients recorded with the specific indication (15-57% and 39-69% for depression respectively). CONCLUSION: Despite applying uniform methods, variations in the prevalence of antidepressant prescribing were obvious in the different populations. Database characteristics and clinical factors may both explain these variations.

BACKGROUND: Barrett's oesophagus (BO) is a risk factor for oesophageal adenocarcinoma (OAC). Several studies report increasing incidences of BO with substantial variation. AIM: To determine age- and sex-stratified incidence rates (IR) of BO and OAC. METHODS: Cohort study using two primary care databases in the United Kingdom (UK) and the Netherlands (NL) (2000-2012). BO and OAC cases were identified using disease-specific READ codes (UK) and free-text search with manual validation (NL). Age- and sex-specific incidence rates (IRs) were calculated for both BO and OAC. RESULTS: From the study population of 6,885,420 subjects in the UK, we identified 12,312 incident BO and 40 (0.3%) subsequent incident OAC cases. There were 1383 incident BO, and subsequent 5 (0.4%) incident OAC cases among the 1,487,191 subjects in the NL. The IR of BO increased linearly with age: 15.6/100,000 PYs (UK) and 23.7/100,000 PYs (NL) for patients aged 40-44 years, increasing to 85.6/100,000 PYs (UK) and 87.0/100,000 PYs (NL) for 70-74 years. In both the UK and the NL, IR of BO was 2-4 times higher in males than females across all age groups. With respect to calendar time, the IR of BO increased by 35% (UK) and 41% (NL) from 2000 to 2003, after which IRs remained stable until 2012. CONCLUSIONS: The incidence rates of BO in the UK and the NL increased until 2003, but levelled off thereafter. Around 0.3% of patients with BO developed OAC at least 1 year after BO diagnosis. These findings may help tailor endoscopic surveillance strategies among patients with BO.

Association between warfarin use and fracture risk is unclear. We examined the association between long-term warfarin use and fracture risk at the hip, spine, and wrist in elders. No significant association was found between long-term warfarin use and fracture risk, despite biological plausibility. INTRODUCTION: Prior studies examining the association of warfarin use and osteoporotic fractures have been conflicting, potentially related to methodological limitations. Thus, we examined the association of long-term warfarin use with risk of hip, spine, and wrist fractures among older adults with atrial fibrillation, attempting to address prior methodologic challenges. METHODS: We included men and women ≥ 65 years of age with incident atrial fibrillation and without prior history of fractures from The Health Improvement Network followed between 2000 and 2010. Long-term warfarin use was defined in two ways: (1) warfarin use ≥ 1 year; (2) warfarin use ≥ 3 years. Propensity-score matched cohorts of warfarin users and nonusers were created to evaluate the association between long-term warfarin use and risk of hip, spine, and wrist fractures separately as well as combined, using Cox-proportional hazards regression models. RESULTS: Among >20,000 participants with incident atrial fibrillation, the hazard ratios (HR) for hip fracture with warfarin use ≥ 1 and ≥ 3 years, respectively, were 1.08 (95%CI 0.87, 1.35) and 1.13 (95% CI 0.84, 1.50). Similarly, no significant associations were observed between long-term warfarin use and risk of spine or wrist fracture. When risk of any fracture was assessed with warfarin use, no association was found [HR for warfarin use ≥ 1 year 0.92 (95%CI 0.77, 1.10); HR for warfarin use ≥ 3 years 1.12 (95%CI 0.88, 1.43)]. CONCLUSIONS: Long-term warfarin use among elders with atrial fibrillation was not associated with increased risk of osteoporotic fractures and therefore does not appear to necessitate additional surveillance or prophylaxis.

Hip fractures represent a major public health challenge worldwide. Multinational studies using a common methodology are scarce. We aimed to estimate the incidence rates (IRs) and trends of hip/femur fractures over the period 2003-2009 in five European countries. The study was performed using seven electronic health-care records databases (DBs) from Denmark, The Netherlands, Germany, Spain, and the United Kingdom, based on the same protocol. Yearly IRs of hip/femur fractures were calculated for the general population and for those aged ≥50 years. Trends over time were evaluated using linear regression analysis for both crude and standardized IRs. Sex- and age-standardized IRs for the UK, Netherlands, and Spanish DBs varied from 9 to 11 per 10,000 person-years for the general population and from 22 to 26 for those ≥50 years old; the German DB showed slightly higher IRs (about 13 and 30, respectively), whereas the Danish DB yielded IRs twofold higher (19 and 52, respectively). IRs increased exponentially with age in both sexes. The ratio of females to males was ≥2 for patients aged ≥70-79 years in most DBs. Statistically significant trends over time were only shown for the UK DB (CPRD) (+0.7% per year, P < 0.01) and the Danish DB (-1.4% per year, P < 0.01). IRs of hip/femur fractures varied greatly across European countries. With the exception of Denmark, no decreasing trend was observed over the study period.