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BackgroundLong-term outcomes for Medicare beneficiaries hospitalised with transient ischaemic attack (TIA) and role of ABCD2 score in identifying high-risk individuals are not studied.MethodsWe identified 40 825 Medicare beneficiaries hospitalised from 2011 to 2014 for a TIA to a Get With The Guidelines (GWTG)-Stroke hospital and classified them using ABCD2 score. Proportional hazards models were used to assess 1-year event rates of mortality and rehospitalisation (all-cause, ischaemic stroke, haemorrhagic stroke, myocardial infarction, and gastrointestinal and intracranial haemorrhage) for high-risk versus low-risk groups adjusted for patient and hospital characteristics.ResultsOf the 40 825 patients, 35 118 (86%) were high risk (ABCD2 ≥4) and 5707 (14%) were low risk (ABCD2=0–3). Overall rate of mortality during 1-year follow-up after hospital discharge for the index TIA was 11.7%, 44.3% were rehospitalised for any reason and 3.6% were readmitted due to stroke. Patients with ABCD2 score ≥4 had higher mortality at 1 year than not (adjusted HR 1.18, 95% CI 1.07 to 1.30). Adjusted risks for ischaemic stroke, all-cause readmission and mortality/all-cause readmission at 1 year were also significantly higher for patients with ABCD2 score ≥4 vs 0–3. In contrast, haemorrhagic stroke, myocardial infarction, gastrointestinal bleeding and intracranial haemorrhage risk were not significantly different by ABCD2 score.ConclusionsThis study validates the use of ABCD2 score for long-term risk assessment after TIA in patients aged 65 years and older. Attentive efforts for community-based follow-up care after TIA are needed for ongoing prevention in Medicare beneficiaries who were hospitalised for TIA.

Background A declining trend in mean cholesterol levels and smoking has been observed in high-income western countries during the last few decades, whereas obesity rates have increased. Simultaneously, mortality from coronary heart disease has decreased. The aim of the present study was to determine whether the trends in cardiovascular risk factors have continued in successive cohorts of middle-aged women over a period of 34 years. Methods Six population-based, cross-sectional samples of women (n = 2294) mean age: 49.8 years (range: 45–54), living in Gothenburg, Sweden, were investigated between 1980 and 2014. Results Body mass index (BMI) increased over time, with a mean BMI of 24.7 kg/m2 in 1980 to 25.7 kg/m2 in 2013–2014, corresponding to a weight gain of 4.5 kg, together with an increase in the proportion of obese individuals (BMI ≥ 30 kg/m2) from 10.4 to 16.6% (p = 0.0012). The proportion of smokers and women with hypertension decreased from 34.5 to 12.8% (p = 0.0006) and from 37.7 to 24.5% (p p p Conclusion The trend towards increasing obesity, more leisure-time physical activity and less smoking remains, while the decrease in serum cholesterol appears to have abated.

Chronic limb threatening ischaemia (CLTI) has a high risk of amputation and mortality. Increased knowledge on how sex, comorbidities, and medication influence these outcomes after revascularisation may help optimise results and patient selection.This population based observational cohort study included all individuals revascularised for CLTI in Sweden during a five year period (10,617 patients in total). Data were retrieved and merged from mandatory national healthcare registries, and specifics on amputations were validated with individual medical records.Mean age at revascularisation was 76.8 years. Median follow up was 2.7 years (range 0-6.6 years). Male sex (hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.09-1.33), renal insufficiency (HR 1.57, 95% CI 1.32-1.87), diabetes (HR 1.45, 95% CI 1.32-1.60), and heart failure (HR 1.17, 95% CI 1.05-1.31) were independently associated with an increased amputation rate, whereas the use of statins (HR 0.71, 95% CI 0.64-0.78) and low dose acetylsalicylic acid (HR 0.77, 95% CI 0.70-0.86) were associated with a reduced amputation rate. For the combined end point of amputation or death, an association with increased rates was found for male sex (HR 1.25, 95% CI 1.18-1.32), renal insufficiency (HR 1.94, 95% CI 1.75-2.14), heart failure (HR 1.50, 95% CI 1.40-1.60), and diabetes (HR 1.31, 95% CI 1.23-1.38). The use of statins (HR 0.74, 95% CI 0.67-0.82) and low dose acetylsalicylic acid (HR 0.82, 95% CI 0.77-0.88]) were related to a reduced risk of amputation or death.Renal insufficiency is the strongest independent risk factor for both amputation and amputation/death in revascularised CLTI patients, followed by diabetes and heart failure. Men with CLTI have worse outcomes than women. These results may help govern patient selection for revascularisation procedures. Statin and low dose acetylsalicylic acid are associated with an improved limb outcome. This underlines the importance of preventive medication to reduce general cardiovascular risk and increase limb salvage.

Background Few data are available on risk factors and associations with outcomes in symptomatic peripheral artery disease (PAD) populations in primary care. We assessed characteristics and cardiovascular outcomes in patients with and those without symptomatic peripheral artery disease in UK primary care, and quantified risk factors for cardiovascular outcomes in patients with peripheral artery disease. Methods Among patients in The Health Improvement Network (THIN) aged 50-89 years in 2000-2010, a symptomatic peripheral artery disease cohort ( n = 28,484) and a matched comparison cohort without peripheral artery disease ( n = 113,940) were identified using Read codes. Cox proportional hazard ratios (HRs) and 95% confidence intervals (CIs) for cardiovascular outcomes were calculated, adjusted for potential confounders. Results The incidence of all-cause death per 1000 person-years was 83.22 and 50.46 in the peripheral artery disease and non-peripheral artery disease cohort, respectively (HR 1.41; 95% CI 1.68-1.43). The incidence of composite cardiovascular outcome (myocardial infarction, ischaemic stroke or cardiovascular-related death) per 1000 person-years was 31.87 and 14.63 in the peripheral artery disease and non-peripheral artery disease cohort, respectively (HR 1.71; 95% CI 1.65-1.77). Risk factors for composite cardiovascular outcome in patients with peripheral artery disease were older age (≥75 years vs. 50-64 years: HR 2.37; 95% CI 2.20-2.55), current smoking (1.26; 1.17-1.35), comorbid diabetes (1.42; 1.32-1.52), heart failure (1.31; 1.20-1.44), atrial fibrillation (1.32; 1.18-1.47, previous myocardial infarction (1.29; 1.20-1.39) and previous ischaemic stroke (1.77; 1.63-1.93). Conclusion Patients with symptomatic peripheral artery disease in a clinical practice population have a high risk of death and cardiovascular-related outcomes. Minimising risk is important in the ongoing management of these patients.

Purpose Discontinuing low-dose acetylsalicylic acid (ASA) therapy after upper gastrointestinal bleeding (UGIB) may increase the risk of cardiovascular-related death. Our aim was to compare mortality in UK primary care patients who discontinue ASA after UGIB with that in patients who continue therapy. Methods ASA users at the time of UGIB and who were alive 30 days after were selected using The Health Improvement Network. Predictors of survival were assessed using adjusted Cox proportional hazards regression models. Results Of 547 ASA users, half did not re-initiate ASA during a mean follow-up of 4.1 years. Increasing age (a 10% increased risk for each yearly increase in age; hazard ratio [HR]: 1.10; 95% confidence interval [CI]: 1.07–1.14), female sex (HR: 1.61; 95%CI: 1.09–2.38), current smoking (HR: 2.11; 95%CI: 1.23–3.63), heavy alcohol use (HR: 3.31; 95%CI: 1.50–7.31), diabetes mellitus (HR: 1.93; 95%CI: 1.25–3.00), and chronic obstructive pulmonary disease (HR: 1.75; 95%CI: 1.03–2.99) were significantly associated with increased mortality. Most deaths (115/139) occurred in patients taking ASA for secondary prevention. In these patients, mortality tended to be lower among ASA continuer periods (HR: 0.74; 95%CI: 0.34–1.62) and higher among discontinuer periods (HR: 1.37; 95%CI: 0.81–2.30) than among non-users. Current use of clopidogrel was associated with decreased mortality in this population (HR: 0.49; 95%CI: 0.28–0.86). Conclusions ASA therapy for secondary prevention should continue after UGIB because the risk of death tends to increase when ASA is stopped. However, a significantly increased risk was not found in these patients, likely owing to the relatively small number of ASA users and deaths that occurred during follow-up. Further studies with larger samples sizes are needed to confirm these findings among UGIB survivors taking ASA at the time of UGIB. Copyright © 2016 John Wiley & Sons, Ltd.

Objectives Longitudinal data are limited regarding outcomes and costs beyond one year after acute myocardial infarction (MI) among elderly (≥65 years old) United States patients. This study examined long-term outcomes and healthcare costs among elderly MI survivors. Methods .Retrospective analysis of 2002–2009 Medicare healthcare claims (5% random sample). Patients were ≥65 years old and survived ≥1 year without recurrent MI after MI hospitalization. Mortality, incidence of hospitalizations for stroke, major bleeding, MI, a composite endpoint (death, MI or stroke), and non-pharmacy healthcare costs were determined. Results Eligible patients included 16,244 STEMI, 34,576 NSTEMI, and 3,109 unspecified MI. NSTEMI and unspecified MI patients had significantly higher prevalence of comorbidities than STEMI patients, except for hypertension and dyslipidemia. MI incidence declined 36% over the follow-up (3.82/100 person years [PY] to 2.45/100 PY). Mortality, stroke, and bleeding decreased until the third year of follow-up and then increased. NSTEMI and unspecified MI patients had a significantly higher incidence of death, MI, the composite, and bleeding than STEMI patients throughout follow-up. All-cause inpatient costs during follow-up were 2.6- and 1.9-fold higher than baseline for STEMI and NSTEMI, respectively; cardiovascular-related inpatient costs were 3.5- and 2.2-fold higher, respectively. Conclusions Risks of mortality and cardiovascular events remain high in a Medicare population surviving >1 year after a MI. Continuing healthcare costs are doubled over pre-MI levels up to five years after an MI. Secondary prevention measures beyond the acute post-MI period may be indicated to reduce risk and cost in this chronic disease phase. This article is protected by copyright. All rights reserved.

Objectives Our purpose was to explore major vascular and bleeding outcomes in relation to risk and severity scores (ABCD2 or NIHSS) in patients with transient ischemic attack (TIA) or acute ischemic stroke (AIS). Methods This nationwide observational study was based on data from 4 national registries. Outcomes were assessed by Kaplan-Meier and Cox regression analyses. Results The total cohort comprised 21 268 patients (median age 73 years, 47.6% females). Based on ABCD2-score, the TIA-population (n = 10 174) was divided into low-risk (0-3 p, n = 3463) and high-risk (4-7 p, n = 6711). Based on NIHSS-score, the AIS-population (n = 11 454) was divided into minor (0-5 p, n = 8596), moderate (6-10 p, n = 1630) and severe (≥11 p, n = 1228). During follow-up (mean 1.7 years), the composite endpoint of stroke, myocardial infarction or death occurred in 3572 (16.5%) of all the patients, and major bleeding in 668 (3.1%) patients. Using low-risk TIA as reference, the adjusted hazard ratios (HR, 95% CI) of the composite endpoint were 1.41 (1.23-1.62) for high-risk TIA, 1.94 (1.70-2.22) for minor, 2.86 (2.45-3.34) for moderate and 4.18 (3.57-4.90) for severe stroke. When analyzed separately, the association with increased risk remained significant for stroke and death, but not for myocardial infarction. The HR of major bleeding were 1.31 (0.99-1.73) for high-risk TIA, 1.49 (1.13-1.95) for minor, 1.54 (1.08-2.21) for moderate and 2.10 (1.44-3.05) for severe stroke. Conclusions This study confirms the association between severity of the index ischemic stroke and risk of future major vascular and bleeding events, and highlights the increased risk also for patients with high-risk TIA.

The purpose of this analysis was to assess potential predictors of intra-cranial bleeding (ICB) and gastrointestinal bleeding (GIB) in patients with symptomatic peripheral artery disease (PAD) in UK primary care. Patients with symptomatic PAD diagnosed from 2000 to 2010 were identified from The Health Improvement Network (THIN; N = 28,484). A nested case–control analysis, adjusted for potential confounders, was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for potential predictors of ICB or GIB. For GIB, follow-up was restricted to Hospital Episode Statistics-linked THIN practices. Median follow-up was 6 years. For ICB (153 cases), the OR (95% CI) was 3.85 (1.33–11.13) for previous ICB, 0.90 (0.61–1.34) for treated hypertension, 1.59 (0.65–3.87) for untreated hypertension and 1.38 (0.80–2.36) for current smoking. ORs for ICB were 0.78 (0.50–1.21), 0.40 (0.09–1.82) and 1.27 (0.47–3.47) with use of acetylsalicylic acid (ASA), clopidogrel and warfarin monotherapy, respectively, compared with non-use of such therapy. For GIB (506 cases), the OR was 1.40 (1.05–1.86) for peptic ulcer disease, 3.20 (1.81–5.64) for dual anti-platelet therapy use, 1.96 (1.46–2.64) for non-steroidal anti-inflammatory drug (NSAID) use and 1.01 (0.80–1.28) for proton pump inhibitor use. ORs for GIB were 1.78 (1.39–2.30), 2.03 (1.05–3.93) and 1.25 (0.72–2.16) with ASA, clopidogrel and warfarin monotherapy, respectively, compared with non-use. Previous ICB was a risk factor for ICB. Use of anti-platelet therapy or NSAIDs increased GIB risk. Identifying bleeding predictors could help optimize treatment strategies for patients with PAD.

Background Long‐term disease progression after myocardial infarction ( MI ) is inadequately understood. We evaluated the pattern and angiographic properties (culprit lesion [ CL ]/non‐CL [ NCL ]) of recurrent MI (re‐ MI ) in a large real‐world patient population. Methods and Results Our observational study used prospectively collected data in 108 615 patients with first‐occurrence MI enrolled in the SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence‐Based Care in Heart Disease Evaluated According to Recommended Therapies) between July 1, 2006 and November 29, 2014. During follow‐up (median, 3.2 years), recurrent hospitalization for MI occurred in 11 117 patients (10.2%). Of the patients who underwent coronary angiography for the index MI , a CL was identified in 44 332 patients. Of those patients, 3464 experienced an re‐ MI ; the infarct originated from the NCL in 1243 patients and from the CL in 655 patients. In total, 1566 re‐ MI s were indeterminate events and could not be classified as NCL or CL re‐MIs. The risk of re‐ MI within 8 years related to the NCL was 0.06 (95% confidence interval [CI], 0.05–0.06), compared with 0.03 (95% CI , 0.02–0.03) for the CL . There were no large differences in baseline characteristics of patients with subsequent NCL versus CL re‐ MI s. Independent predictors of NCL versus CL re‐ MI were multivessel disease (odds ratio, 2.29; 95% CI , 1.87–2.82), male sex (odds ratio, 1.36; 95% CI, 1.09–1.71), and a prolonged time between the index and re‐MI (odds ratio, 1.16; 95% CI , 1.10–1.22). Conclusions In a large cohort of patients with first‐occurrence MI undergoing percutaneous coronary intervention, the risk of re‐MI originating from a previously untreated lesion was twice higher than the risk of lesions originating from a previously stented lesion. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 03099395.

Summary Background Some research has suggested a potential link between prenatal exposure to proton pump inhibitors (PPIs) or H2-receptor antagonists (H2RAs) and the development of childhood asthma. Aim To quantify the relative risk of asthma in children who experienced pre-natal exposure to PPIs and/or H2RAs, adjusting for potential confounders. Methods In this observational cohort study (NCT01787435), women aged 18–45 years with completed pregnancies between January 1996 and December 2010 were identified from The Health Improvement Network in the United Kingdom, and were linked to infants. Hazard ratios (HRs) were estimated using Cox proportional hazard models. Results Our analysis identified 2371 prenatally exposed and 7745 unexposed infants. The incidence of asthma (per 1000 person-years) was 19.52 in the unexposed cohort, 23.88 in the PPI cohort and 32.16 in the H2RA cohort. After adjusting for maternal healthcare utilisation during the year before pregnancy, the HR for asthma in infants whose mothers received prescriptions at any time during pregnancy was 1.12 (95% confidence interval: 0.88–1.44) for PPIs and 1.43 (1.20–1.70) for H2RAs, when compared with unexposed infants. With further adjustment for maternal comorbidities and other medications, the HR for asthma was 1.03 (0.76–1.40) for PPIs and 1.32 (1.05–1.64) for H2RAs. Conclusions Our analysis showed no association between prenatal exposure to PPIs and asthma in childhood after adjusting for confounders. The association found for H2RAs may be explained largely by underlying environmental or genetic factors, as suggested by reductions in hazard ratio estimates following adjustment for maternal comorbidities.

In secondary cardiovascular prevention, discontinuation of acetylsalicylic acid (ASA) is associated with an increased risk of cardiovascular events. This study assessed the impact of ASA reinitiation on the risk of myocardial infarction and coronary heart disease death.Patients prescribed ASA for secondary cardiovascular prevention and who had had a period of ASA discontinuation of ≥90 days in 2000-2007 were identified from The Health Improvement Network (N = 10,453). Incidence of myocardial infarction/coronary heart disease death was calculated. Survival analyses using adjusted Cox proportional hazard models were performed to calculate hazard ratios and 95% confidence intervals for the risk of myocardial infarction/coronary heart disease death associated with ASA use patterns after the initial period of discontinuation. Individuals who were prescribed ASA during follow-up were considered reinitiators.The incidence of myocardial infarction/coronary heart disease death was 8.90 cases per 1000 person-years. Risk of myocardial infarction/coronary heart disease death was similar for current ASA users, who had been continuously exposed since reinitiation, and patients who had not reinitiated ASA (hazard ratio 1.27, 95% confidence interval 0.93-1.73). Among reinitiators, an additional period of ASA discontinuation was associated with increased risk of myocardial infarction/coronary heart disease death compared with no reinitiation (current users: hazard ratio 1.46, 95% confidence interval 1.13-1.90; noncurrent users: hazard ratio 1.70, 95% confidence interval 1.31-2.21).ASA reinitiation was not associated with a decreased risk of myocardial infarction/coronary heart disease death. This may be explained by confounding by indication/comorbidity, whereby higher-risk patients are more likely to reinitiate therapy. An additional period of ASA discontinuation among reinitiators was associated with an increased risk of myocardial infarction/coronary heart disease death.

Background The use of antithrombotic drugs (anticoagulants and antiplatelet drugs) has been reported to increase the risk of hemorrhagic stroke (HS) relative to no treatment. This study was performed to characterize the incidence and predictors of HS in users of acetylsalicylic acid (ASA) for the secondary prevention of cardiovascular events. Methods A cohort of 36,775 ASA users aged 50-84 years in 2000-2007 was identified from The Health Improvement Network database. The incidence of HS was calculated, and a nested case–control analysis, adjusted for potential confounding factors, was performed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the association of potential risk factors with HS in current users of ASA. Results The overall incidence of HS was 5.70 cases per 10,000 person-years and increased with age. In current ASA users, the incidence of HS was 4.91 cases per 10,000 person-years. Predictors of HS in patients taking ASA for secondary prevention included a history of HS (OR, 4.84; 95% CI, 1.48-15.88), a history of atrial fibrillation (OR, 4.03; 95% CI, 1.53-10.62), and hypnotic/anxiolytic drug use (OR, 2.67; 95% CI, 1.17-6.05). The small number of patients using warfarin also had an increased risk of HS (OR, 23.42; 95% CI, 4.89-112.10). Conclusions Physicians should consider additional risk factors for HS, such as a history of HS or atrial fibrillation, and the use of warfarin, before prescribing ASA for the secondary prevention of cardiovascular events.

PURPOSE: Studies on drug utilization usually do not allow direct cross-national comparisons because of differences in the respective applied methods. This study aimed to compare time trends in BZDs prescribing by applying a common protocol and analyses plan in seven European electronic healthcare databases. METHODS: Crude and standardized prevalence rates of drug prescribing from 2001-2009 were calculated in databases from Spain, United Kingdon (UK), The Netherlands, Germany and Denmark. Prevalence was stratified by age, sex, BZD type [(using ATC codes), i.e. BZD-anxiolytics BZD-hypnotics, BZD-related drugs and clomethiazole], indication and number of prescription. RESULTS: Crude prevalence rates of BZDs prescribing ranged from 570 to 1700 per 10 000 person-years over the study period. Standardization by age and sex did not substantially change the differences. Standardized prevalence rates increased in the Spanish (+13%) and UK databases (+2% and +8%) over the study period, while they decreased in the Dutch databases (-4% and -22%), the German (-12%) and Danish (-26%) database. Prevalence of anxiolytics outweighed that of hypnotics in the Spanish, Dutch and Bavarian databases, but the reverse was shown in the UK and Danish databases. Prevalence rates consistently increased with age and were two-fold higher in women than in men in all databases. A median of 18% of users received 10 or more prescriptions in 2008. CONCLUSION: Although similar methods were applied, the prevalence of BZD prescribing varied considerably across different populations. Clinical factors related to BZDs and characteristics of the databases may explain these differences. Copyright © 2015 John Wiley & Sons, Ltd. Language: en

BACKGROUND: Results from observational studies may be inconsistent because of variations in methodological and clinical factors that may be intrinsically related to the database (DB) where the study is performed. OBJECTIVES: The objectives of this paper were to evaluate the impact of applying a common study protocol to study benzodiazepines (BZDs) (anxiolytics, hypnotics, and related drugs) and the risk of hip/femur fracture (HFF) across three European primary care DBs and to investigate any resulting discrepancies. METHODS: To measure the risk of HFF among adult users of BZDs during 2001-2009, three cohort and nested case control (NCC) studies were performed in Base de datos para la Investigacion Farmacoepidemiologica en Atencion Primaria (BIFAP) (Spain), Clinical Practice Research Datalink (CPRD) (UK), and Mondriaan (The Netherlands). Four different models (A-D) with increasing levels of adjustment were analyzed. The risk according to duration and type of BZD was also explored. Adjusted hazard ratios (cohort), odds ratios (NCC), and their 95% confidence intervals were estimated. RESULTS: Adjusted hazard ratios (Model C) were 1.34 (1.23-1.47) in BIFAP, 1.66 (1.54-1.78) in CPRD, and 2.22 (1.55-3.29) in Mondriaan in cohort studies. Adjusted odds ratios (Model C) were 1.28 (1.16-1.42) in BIFAP, 1.60 (1.49-1.72) in CPRD, and 1.48 (0.89-2.48) in Mondriaan in NCC studies. A short-term effect was suggested in Mondriaan, but not in CPRD or BIFAP. All DBs showed an increased risk with the concomitant use of anxiolytic and hypnotic drugs. CONCLUSIONS: Applying similar study methods to different populations and DBs showed an increased risk of HFF in BZDs users but differed in the magnitude of the risk, which may be because of inherent differences between DBs. Copyright © 2015 John Wiley & Sons, Ltd.

Objective: Acid suppression with histamine-2 receptor antagonists (H2RAs) or proton pump inhibitors (PPIs) is recommended for children with persistent gastroesophageal reflux disease symptoms. In this retrospective, observational postauthorization study, we aimed to assess and compare safety outcomes in pediatric first-time users of esomeprazole, other PPIs or H2RAs. Methods: Data on children (aged 0–18 years) first dispensed esomeprazole, other PPIs or H2RAs between September 2008 and August 2011 was obtained from the Dutch PHARMO Database Network. Hospitalizations for seven predefined safety outcomes were evaluated (maximum follow-up: 18 months). Rate ratios were calculated using Poisson regression adjusted for baseline imbalances. Discharge letters were reviewed for event occurrence confirmation. Results: Of 23,470 included children, 2820 (median age: 3 years) were prescribed esomeprazole, 13,818 (median age: 15 years) other PPIs and 6832 (median age: 5 years) H2RAs. In total, 504 (2%) children were hospitalized for 762 predefined events: gastroenteritis (246); convulsion/seizure (200); pneumonia (154); failure to thrive (119); acute interstitial nephritis (19); thrombocytopenia (23); and angioneurotic edema (1). Significant differences between cohorts were observed only for failure to thrive, with adjusted rate ratios (95% confidence interval) for esomeprazole of 6.1 (2.4–15.7) vs. other PPIs and 6.1 (2.9–12.8) vs. H2RAs among current users. Occurrence was confirmed for 74% of assessable events. Confirmation rates were highest for pneumonia (81%) and lowest for failure to thrive (40%). Conclusions: Hospitalization rates for predefined outcomes were low and mostly similar in pediatric first-time users of PPIs and of H2RAs. Trial registration: NCT01338363.

Background: Little is known about the use of acid-suppressing treatments and related safety events in children. Objective: This study compared patient characteristics and safety outcomes among children prescribed acid-suppressing drugs for the first time. Methods: The Health Improvement Network was used to determine the characteristics of children prescribed a proton pump inhibitor (PPI; esomeprazole or another PPI) or a histamine-2 receptor antagonist (H2RA) by UK primary care physicians between October 2009 and September 2012. Pre-defined safety outcomes were compared among the treatment groups in up to 18 months of follow-up. Results: The cohorts comprised 8,172 patients on PPIs (including 24 patients on esomeprazole) and 7,905 on H2RAs. The baseline characteristics were similar between cohorts, although the children in the PPI cohorts tended to be older. No safety outcomes occurred in the esomeprazole cohort. In the other-PPIs cohort, 92 safety outcomes occurred, most commonly gastroenteritis (n = 36; 39.1%). In the H2RAs cohort, 193 safety outcomes occurred, most commonly gastroenteritis (n = 62; 32.1%). The incidence of most safety outcomes was higher in the H2RAs cohort than in the other-PPIs cohort, including failure to thrive (3.11 [95% confidence interval (CI) = 2.25–4.28] vs 0.49 per 1,000 person-years [95% CI = 0.22–1.07]) and gastroenteritis (5.27 [95% CI = 4.11–6.75] vs 3.04 per 1,000 person-years [95% CI = 2.20–4.20]). Conclusion: Esomeprazole is rarely prescribed to children when they first require acid-suppressing medication, compared with other PPIs/H2RAs. Overall, more safety outcomes occurred in the H2RAs cohort than in the PPI cohorts.

Background and Purpose— Patients with minor ischemic stroke or transient ischemic attack are at high risk of recurrent stroke and vascular events, which are potentially disabling or fatal. This study aimed to evaluate contemporary subsequent vascular event risk after minor ischemic stroke or transient ischemic attack in Korea. Methods— Patients with minor ischemic stroke or high-risk transient ischemic attack admitted within 7 days of symptom onset were identified from a Korean multicenter stroke registry database. We estimated 3-month and 1-year event rates of the primary outcome (composite of stroke recurrence, myocardial infarction, or all-cause death), stroke recurrence, a major vascular event (composite of stroke recurrence, myocardial infarction, or vascular death), and all-cause death and explored differences in clinical characteristics and event rates according to antithrombotic strategies at discharge. Results— Of 9506 patients enrolled in this study, 93.8% underwent angiographic assessment and 72.7% underwent cardiac evaluations; 25.1% had symptomatic stenosis or occlusion of intracranial arteries. At discharge, 95.2% of patients received antithrombotics (antiplatelet polytherapy, 37.1%; anticoagulation, 15.3%) and 86.2% received statins. The 3-month cumulative event rate was 5.9% for the primary outcome, 4.3% for stroke recurrence, 4.6% for a major vascular event, and 2.0% for all-cause death. Corresponding values at 1 year were 9.3%, 6.1%, 6.7%, and 4.1%, respectively. Patients receiving nonaspirin antithrombotic strategies or no antithrombotic agent had higher baseline risk profiles and at least 1.5× higher event rates for clinical event outcomes than those with aspirin monotherapy. Conclusions— Contemporary secondary stroke prevention strategies based on thorough diagnostic evaluation may contribute to the low subsequent vascular event rates observed in real-world clinical practice in Korea.

Aims: Data on long-term healthcare costs of patients with peripheral artery disease (PAD) is limited, and the aim of this study was to investigate healthcare costs for PAD patients at a nationwide level. Methods and results: A cohort study including all incident patients diagnosed with PAD in the Swedish National Patient Register between 2006-2014, and linked to cause of death- and prescribed drug registers. Mean per-patient annual healthcare costs (2015 Euros [€]) (hospitalisations and out-patient visits) were divided into cardiovascular (CV), lower limb and non-CV related cost. Results were stratified by high and low CV risk. The study included 66,189 patients, with 221,953 observation-years. Mean total healthcare costs were €6,577, of which 26% was CV-related (€1,710), during the year prior to the PAD diagnosis. First year after PAD diagnosis, healthcare costs were €12,549, of which €3,824 (30%) was CV-related and €3,201 (26%) lower limb related. Highrisk CV patients had a higher annual total healthcare and CV related costs compared to low risk CV patients during follow-up €7,439 and €1,442 versus €4,063 and €838). Annual lower limb procedure costs were €728 in the PAD population, with lower limb revascularisations as key cost driver (€474). Conclusion: Non-CV related hospitalizations and outpatient visits were the largest cost contributors for PAD patients. There is a substantial increase in healthcare costs in the first year after being diagnosed with PAD, driven by PAD follow-up and lower limb related procedures. Among the CV-related costs, hospitalisations and outpatient visits related to PAD represented the largest costs. Keywords Nationwide register data • peripheral artery disease • healthcare resource use • healthcare costs

Background Most studies of outcomes after myocardial infarction (MI) focus on the acute phase after the index event. We assessed mortality and morbidity trends after the first year in survivors of acute MI, by conducting a systematic literature review. Methods Literature searches were conducted in Embase, MEDLINE, and the Cochrane Database of Systematic Reviews to identify epidemiological studies of long-term (>10 years) mortality and morbidity trends in individuals who had experienced an acute MI more than 1 year previously. Results Thirteen articles met the inclusion criteria. Secular trends showed a consistent decrease in mortality and morbidity after acute MI from early to more recent study periods. The relative risk for all-cause death and cardiovascular outcomes (recurrent MI, cardiovascular death) was at least 30% higher than that in a general reference population at both 1–3 years and 3–5 years after MI. Risk factors leading to worse outcomes after MI included comorbid diabetes, hypertension and peripheral artery disease, older age, reduced renal function, and history of stroke. Conclusions There have been consistent improvements in secular trends for long-term survival and cardiovascular outcomes after MI. However, MI survivors remain at higher risk than the general population, particularly when additional risk factors such as diabetes, hypertension, or older age are present.

Background: Antiplatelet (AP) therapy is well established for the secondary prevention of acute coronary events. However, patients may discontinue treatment, often owing to gastrointestinal (GI) complications, leaving them at elevated risk of recurrent cardiovascular events. Objectives: This descriptive retrospective study assessed trends in prescription of AP agents and coprescription of gastroprotective therapy, after an acute coronary event. Discontinuation of AP therapy within 2 years of an event and factors predicting discontinuation were investigated. Methods: The study was conducted in a UK primary care setting from 2000 to 2008; a total of 27 351 patients aged 50 to 84 years were included in the analysis. Main outcome measures were exposures to low-dose acetylsalicylic acid (ASA), clopidogrel, and proton pump inhibitors (PPIs). Results: At 90 days after an acute coronary event, 85.9% of patients had been prescribed some form of AP therapy and 33.6% of patients who were issued at least 1 ASA prescription in this period were also issued a PPI prescription. The use of dual antiplatelet therapy (DAT) 90 days after an event increased from 2% in 2000 to over 50% in 2008. An estimated 15.1% of patients on ASA monotherapy and 37.5% on DAT discontinued treatment within 1 year. A bleeding event during follow-up, including upper GI bleeding or hemorrhagic stroke, was the strongest predictor of discontinuation. Conclusion: Although most patients were prescribed AP therapy in the 90 days following an acute coronary event, a substantial proportion discontinued DAT or ASA monotherapy within 1 year. It is essential that physicians consider strategies to reduce the risk of discontinuation of AP therapy.

Anticoagulants and/or antiplatelet agents such as acetylsalicylic acid (ASA) are important in prevention of cardiovascular (CV) events, but may be associated with upper gastrointestinal bleeding (UGIB). However, discontinuing these agents may leave patients at risk of CV events. This study aimed to assess patterns of therapy after UGIB in routine clinical practice. The Health Improvement Network UK primary care database was used to identify a cohort of patients aged 40–84 years with a UGIB event between 2000 and 2007 (n = 2,036). Patients were followed up for 1 year from the recorded UGIB. Re-prescription rates for antithrombotics and drugs that can modify the risk of UGIB were estimated at 30, 90, 180, and 365 days. At 365 days, the re-prescription rate was 43 % for ASA, 66 % for warfarin, 69 % for clopidogrel, and 49 % for dipyridamole. The re-prescription rate of gastroprotective agents at 365 days for current users of histamine H2-receptor antagonists was 36 % and that of proton pump inhibitors (PPIs) was 97 %. In patients who were prescribed ASA before UGIB (n = 572), only 24 % were prescribed a PPI in the previous year. In patients who were prescribed ASA in the year after UGIB (n = 337), 92 % were prescribed a PPI. Antiplatelet use fell after UGIB events. In patients who were prescribed a PPI after a UGIB event, there was increased re-prescription of antiplatelet agents and antithrombotics.

Objectives We aimed to clarify the nature of the association between hip fracture risk and use of proton pump inhibitors (PPIs) or histamine2-receptor antagonists (H2RAs). Methods We identified patients 40–89 years of age with a recorded hip fracture diagnosis in 2000–2008 using The Health Improvement Network, a UK primary care research database. Computerized records were reviewed and questionnaires sent to primary care physicians to validate hip fracture cases. A cohort study with a nested case-control analysis was performed to estimate the association between the use of acid-suppressive drugs and hip fracture. Results Overall incidence of hip fracture per 1000 person-years was 1.31 (95% confidence interval [CI] 1.28–1.33). There was a modest increased risk of hip fracture after adjustment for potential confounders (odds ratios [OR] during current use of PPIs and H2RAs: 1.09 [95% CI 1.01–1.17] and 1.04 [95% CI 0.90–1.19], respectively). Relative to nonuse, an increased risk of fracture was observed with medium and high doses of PPIs (OR 1.11 [95% CI 1.01–1.22] and OR 1.31 [95% CI 1.06–1.61], respectively) and high doses of H2RAs (OR 2.77, 95% CI 1.21–6.37). No duration response was observed (ORs for current PPI use less than 1 month and 5 years or longer: 1.16 [95% CI 0.94–1.43] and 1.02 [95% CI 0.87–1.20], respectively). Conclusions Patients treated with PPIs showed a modest increased risk of hip fracture after adjustment for potential cofounders. Any remaining association between PPI use and hip fracture risk may be attributable to residual confounding.

SummaryThis study evaluated the risk of cardiovascular events associated with the use of proton pump inhibitors (PPIs) in new users of acetylsalicylic acid (ASA) for the secondary prevention of cardiovascular events. Two cohorts of patients aged 50–84 years were identified from UK primary care databases: individuals with a first prescription for ASA (75−300 mg/day) for secondary prevention of cardiovascular events (n = 39,513; CVD cohort) or with a record of hospitalisation for an acute coronary event (n = 42,542; ACS cohort) in 2000–2007. Cases of nonfatal myocardial infarction (MI) and coronary death were identified: 1,222 in the CVD cohort and 604 among new users of ASA in the ACS cohort. A nested case–control analysis estimated the relative risk (RR) of non-fatal MI or coronary death associated with use vs non-use of PPI therapy. Current continuous use of PPI therapy was not associated with a significant increase in RR overall: in the CVD cohort (RR = 1.14 [95% confidence interval = 0.91−1.43]); in the ACS cohort (0.88 [0.66−1.18]); or among current continuous users of ASA as antiplatelet monotherapy (CVD cohort: 1.15 [0.80−1.66]; ACS cohort: 0.73 [0.43−1.23]; pooled analysis of both cohorts: 0.96 [0.62−1.48]). In conclusion, among first-time users of ASA for the secondary prevention of cardiovascular events, PPI use was not shown to be associated with an increased risk of non-fatal MI or coronary death.

Background Bleeding events have been associated with the use of antiplatelet agents. This study estimated the incidence of bleeding events in patients previously hospitalized for a serious coronary event and determined the risks of bleeding associated with the use of acetylsalicylic acid (ASA) and/or clopidogrel. Methods A UK primary care database was used to identify 27,707 patients aged 50 to 84 years, hospitalized for a serious coronary event during 2000 to 2007 and who were alive 30 days later (start date). Patients were followed up until they reached an endpoint (hemorrhagic stroke, upper or lower gastrointestinal bleeding [UGIB/LGIB]), death or end of study [June 30, 2011]) or met an exclusion criterion. Risk factors for bleeding were determined in a nested case-control analysis. Results Incidences of hemorrhagic stroke, UGIB, and LGIB were 5.0, 11.9, and 25.5 events per 10,000 person-years, respectively, and increased with age. UGIB and LGIB led to hospitalization in 73 and 23 % of patients, respectively. Non-users of ASA, who were mostly discontinuers, and current users of ASA had similar risks of hemorrhagic stroke, UGIB, and LGIB. Users of combined antithrombotic therapy (warfarin and antiplatelets) experienced an increased risk of hemorrhagic stroke (odds ratio [OR], 6.36; 95 % confidence interval [CI], 1.34–30.16), whereas users of combined antiplatelet therapy (clopidogrel and ASA) experienced an increased risk of UGIB (OR, 2.42; 95 % CI, 1.09–5.36). An increased risk of LGIB (OR, 1.86; 95 % CI, 1.34–2.57) was also observed in users of clopidogrel. Conclusions In patients previously hospitalized for a serious coronary event, combined antithrombotic therapy was associated with an increased risk of hemorrhagic stroke, whereas combined antiplatelet therapy was associated with an increased risk of UGIB.Non-use of ASA was rare in this population and use of ASA was not associated with a significantly increased risk of hemorrhagic stroke, UGIB, or LGIB. Electronic supplementary material The online version of this article (doi:10.1186/s12872-016-0348-6) contains supplementary material, which is available to authorized users.

Objectives Previous, large, prescription-event monitoring studies in patients receiving PPI therapy recorded instances of convulsion or seizure. The objective of this study was to quantify the relative risk of seizure associated with the use of proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H 2 RAs) in a general population, overall and stratified by epilepsy status, and to determine the effects of demographics and comorbidities. Methods In this observational study ( NCT01744301 ), patients aged 20–84 years in the study period from 1 January 2005 to 31 December 2011 were identified from The Health Improvement Network. In a nested case–control analysis, 8605 patients with seizure were matched to 40 000 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression. Results After adjustment, there were no associations between current PPI use and seizure risk in the overall population (OR: 1.05; 95% CI: 0.87–1.27), the subcohort with epilepsy (OR: 0.87; 95% CI: 0.49–1.53), and the subcohort without epilepsy (OR: 1.05; 95% CI: 0.87–1.28). There were no associations between current H 2 RA use and seizure risk in the overall population (OR: 1.16; 95% CI: 0.62–2.18) and the subcohort without epilepsy (OR: 1.02; 95% CI: 0.51–2.01). Seizures were less frequent in women than in men. Dementia/psychosis, anxiety, depression, and use of anxiolytics, antidepressants, and paracetamol were associated with an increased seizure risk. Conclusions Our study revealed that the use of PPIs and the use of H 2 RAs were not associated with an increased risk of seizures in the overall population or in the cohorts stratified by epilepsy status.

The aim of this systematic literature review was to assess the consequences of dual antiplatelet therapy discontinuation on clinical outcomes after acute coronary syndromes.A systematic literature search was conducted in PubMed to identify studies reporting data on patients who discontinued dual antiplatelet therapy (planned or unplanned) following acute coronary syndromes and on the clinical impact of dual antiplatelet therapy discontinuation. To be included, more than 50% of the study population had to have had acute coronary syndrome as their index event or, if less than 50%, outcomes data must have been reported separately for the group with acute coronary syndromes. Thirty publications covering 29 studies were identified for inclusion. There was much heterogeneity across studies regarding the included patient populations, treatment durations and outcome definitions and ascertainments. Dual antiplatelet therapy discontinuation was most commonly based on physician decision. Twenty-six studies reported that clopidogrel was prescribed as part of dual antiplatelet therapy. Dual antiplatelet therapy duration was positively associated with a lower risk of all-cause mortality (seven/eight studies), cardiovascular mortality (two/two studies), non-fatal myocardial infarction (two/three studies) and stent thrombosis (five/five studies) in patients and/or patient subgroups in studies without randomised treatment designs, although such associations were not observed in the one study that randomly assigned patients to treatment (i.e. planned discontinuation).Results from our systematic literature review generally support the benefit of longer-term dual antiplatelet therapy after acute coronary syndromes; however, further research is needed to determine the optimal length of dual antiplatelet therapy in patients after acute coronary syndrome, ideally using prospective studies.

Discontinuing low-dose acetylsalicylic acid (ASA) therapy after upper gastrointestinal bleeding (UGIB) may increase the risk of cardiovascular-related death. Our aim was to compare mortality in UK primary care patients who discontinue ASA after UGIB with that in patients who continue therapy.ASA users at the time of UGIB and who were alive 30 days after were selected using The Health Improvement Network. Predictors of survival were assessed using adjusted Cox proportional hazards regression models.Of 547 ASA users, half did not re-initiate ASA during a mean follow-up of 4.1 years. Increasing age (a 10% increased risk for each yearly increase in age; hazard ratio [HR]: 1.10; 95% confidence interval [CI]: 1.07-1.14), female sex (HR: 1.61; 95%CI: 1.09-2.38), current smoking (HR: 2.11; 95%CI: 1.23-3.63), heavy alcohol use (HR: 3.31; 95%CI: 1.50-7.31), diabetes mellitus (HR: 1.93; 95%CI: 1.25-3.00), and chronic obstructive pulmonary disease (HR: 1.75; 95%CI: 1.03-2.99) were significantly associated with increased mortality. Most deaths (115/139) occurred in patients taking ASA for secondary prevention. In these patients, mortality tended to be lower among ASA continuer periods (HR: 0.74; 95%CI: 0.34-1.62) and higher among discontinuer periods (HR: 1.37; 95%CI: 0.81-2.30) than among non-users. Current use of clopidogrel was associated with decreased mortality in this population (HR: 0.49; 95%CI: 0.28-0.86).ASA therapy for secondary prevention should continue after UGIB because the risk of death tends to increase when ASA is stopped. However, a significantly increased risk was not found in these patients, likely owing to the relatively small number of ASA users and deaths that occurred during follow-up. Further studies with larger samples sizes are needed to confirm these findings among UGIB survivors taking ASA at the time of UGIB. Copyright © 2016 John WileySons, Ltd.

It has been suggested that the prevalence of Helicobacter pylori infection has stabilized in the USA and is decreasing in China. We conducted a systematic literature analysis to test this hypothesis. PubMed and Embase searches were conducted up to 19 January 2015. Trends in the prevalence of H. pylori infection over time were assessed by regression analysis using Microsoft Excel. Overall, 25 Chinese studies (contributing 28 datasets) and 11 US studies (contributing 11 datasets) were included. There was a significant decrease over time in the H. pylori infection prevalence for the Chinese studies overall (p = 0.00018) and when studies were limited to those that used serum immunoglobulin G (IgG) assays to detect H. pylori infection (p = 0.014; 20 datasets). The weighted mean prevalence of H. pylori infection was 66 % for rural Chinese populations and 47 % for urban Chinese populations. There was a significant trend towards a decreasing prevalence of H. pylori infection for studies that included only urban populations (p = 0.04; 9 datasets). This trend was no longer statistically significant when these studies were further restricted to those that used serum IgG assays to detect H. pylori infection, although this may have been because of low statistical power due to the small number of datasets available for this analysis (p = 0.28; 6 datasets). There were no significant trends in terms of changes in the prevalence of H. pylori infection over time for studies conducted in the USA. In conclusion, the prevalence of H. pylori infection is most likely decreasing in China, due to a combination of increasing urbanization, which we found to be associated with lower H. pylori infection rates, and possibly also decreasing rates of H. pylori infection within urban populations. This will probably result in a gradual decrease in peptic ulcer and gastric cancer rates in China over time. Electronic supplementary material The online version of this article (doi:10.1186/s13099-016-0091-7) contains supplementary material, which is available to authorized users.

Introduction: Patients experiencing a mild ischemic stroke (MIS) or transient ischemic attack (TIA) are at high risk of further events in the next 90 days. A good understanding of the unmet medical needs in these patients is required to develop evidenced-based treatment options that may improve post-stroke outcomes. Aims: This systematic literature review aimed to assess 90-day outcomes in patients following an MIS in routine clinical practice. Methods: Ovid MEDLINE and Embase were searched using terms relating to disease, severity and outcomes. Key inclusion criteria were: ≥ 100 patients with MIS (NIHSS score ≤ 5); 90-day outcomes reported; and non-interventional study design. Results: In total, 6510 records were identified. Of these, 18 articles reporting outcomes from 16 studies were included in the review. Stroke recurrence at 90 days, reported by 7 studies, varied widely (0.9-24.6%; Table); there were differences in study size, recurrence definition and time to presentation. Mortality at 90 days was 0.2-5.1% (13 studies), with a trend towards higher mortality in studies using higher NIHSS cut-off values to define MIS. Most patients had modified Rankin Scale scores of 0-1 (6 studies) or 0-2 (5 studies) at 90 days. Conclusions: The rates of 90-day stroke recurrence in patients following an MIS identified in this comprehensive literature review suggest there is a need for improvement in current clinical practice. However, identified studies reporting stroke recurrence had varied methodologies. Further standardized studies in these patients may be needed to better understand stroke recurrence, severity and mortality.

BACKGROUND: Results from observational studies may be inconsistent because of variations in methodological and clinical factors that may be intrinsically related to the database (DB) where the study is performed. OBJECTIVES: The objectives of this paper were to evaluate the impact of applying a common study protocol to study benzodiazepines (BZDs) (anxiolytics, hypnotics, and related drugs) and the risk of hip/femur fracture (HFF) across three European primary care DBs and to investigate any resulting discrepancies. METHODS: To measure the risk of HFF among adult users of BZDs during 2001-2009, three cohort and nested case control (NCC) studies were performed in Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP) (Spain), Clinical Practice Research Datalink (CPRD) (UK), and Mondriaan (The Netherlands). Four different models (A-D) with increasing levels of adjustment were analyzed. The risk according to duration and type of BZD was also explored. Adjusted hazard ratios (cohort), odds ratios (NCC), and their 95% confidence intervals were estimated. RESULTS: Adjusted hazard ratios (Model C) were 1.34 (1.23-1.47) in BIFAP, 1.66 (1.54-1.78) in CPRD, and 2.22 (1.55-3.29) in Mondriaan in cohort studies. Adjusted odds ratios (Model C) were 1.28 (1.16-1.42) in BIFAP, 1.60 (1.49-1.72) in CPRD, and 1.48 (0.89-2.48) in Mondriaan in NCC studies. A short-term effect was suggested in Mondriaan, but not in CPRD or BIFAP. All DBs showed an increased risk with the concomitant use of anxiolytic and hypnotic drugs. CONCLUSIONS: Applying similar study methods to different populations and DBs showed an increased risk of HFF in BZDs users but differed in the magnitude of the risk, which may be because of inherent differences between DBs. Copyright © 2015 John Wiley & Sons, Ltd.

Up to one-third of patients with gastroesophageal reflux disease (GERD) in primary care have residual symptoms despite proton pump inhibitor (PPI) therapy. We aimed to characterize partial response to PPIs among adult patients in UK primary care.Newly diagnosed GERD patients aged 20-79 years who were prescribed PPI for treatment of GERD were identified in The Health Improvement Network. Those with a treatment change suggesting partial response to PPIs (new treatment added to PPI, increased PPI dose, or switching PPI) during the subsequent 6 months were identified as potential cases and confirmed after manual review of each patient's complete computer medical record including free-text comments. Patients without these treatment changes were study controls. A nested case-control analysis was conducted using logistic regression.The proportion of newly diagnosed GERD patients with partial response to PPI therapy was 18.6% (1201/6453). Partial response was associated with female gender (odds ratio [OR]: 1.20; 95% confidence interval [CI]: 1.05-1.37), anxiety or depression (OR: 1.15; 95% CI: 1.00-1.31), and prescription of ≥ 6 drugs in the month before GERD diagnosis (OR: 1.42; 95% CI: 1.14-1.78). Among new PPI users (n = 2907), partial response was associated with esophageal ulcer or Barrett's esophagus at initial diagnosis (OR: 3.14; 95% CI: 1.60-6.17).Approximately one in five newly diagnosed patients with GERD appear to have a partial response to PPI therapy. Female gender, polymedication, and a severe initial diagnosis may be associated with partial response.

Purpose To determine trends and predictors of clopidogrel and proton pump inhibitor (PPI) coprescription with low-dose acetylsalicylic acid (ASA) prescribed for secondary cardiovascular or cerebrovascular disease (CVD) prevention in UK primary care. Methods Patients aged 50–84 years who received a first prescription for low-dose ASA for secondary CVD prevention in 2000–2001 (n = 10 330) or 2006–2007 (n = 8154) were identified in The Health Improvement Network UK primary care database. Clopidogrel or PPI coprescriptions received within 15 days after the first low-dose ASA prescription were ascertained. Results Clopidogrel coprescription with low-dose ASA increased from 1.6% to 25.2% between the two study periods; PPI coprescription increased from 11.6% to 28.3%. Low-dose ASA indications of myocardial infarction [odds ratio (OR) 11.7, 95% confidence interval (CI) 10.2 to 13.4] and unstable angina (OR 1.73, 95%CI 1.09 to 2.75) were positive predictors of clopidogrel coprescription in 2006–2007, relative to chronic ischaemic heart disease. Patients at high risk of upper gastrointestinal bleeding were more likely to receive a PPI than those at lower risk in 2006–2007 (OR 4.36, 95%CI 3.93 to 4.84). In this period, 65.5% of patients who required a clopidogrel coprescription according to guideline recommendations received one, and 44.3% of patients at high risk of upper gastrointestinal bleeding received a PPI. Conclusion Clopidogrel and PPI coprescription with low-dose ASA increased markedly between 2000–2001 and 2006–2007; however, many patients on low-dose ASA did not receive the recommended coprescriptions at the end of the study period. Copyright © 2012 John Wiley & Sons, Ltd.

Objectives The aims of this population based study were to describe mid- to long-term amputation risk, cumulative incidence of death or amputation, and differences in pre-operative comorbidities in patients revascularised for lower limb peripheral artery disease (PAD). Methods This was an observational cohort study. Data from the Swedish National Quality Registry for Vascular Surgery (Swedvasc) were combined with mandatory national health care registries and patient medical records. All patients who underwent revascularisation in Sweden between May 2008 and May 2013 for intermittent claudication (IC) or critical limb ischaemia (CLI), aged 50 years and older, were identified through the Swedvasc database. The mandatory national health care registries and medical records provided data on comorbidities, mortality, and major amputations. Results A total of 16,889 patients with PAD (IC, n = 6272; CLI, n = 10,617) were studied. The incidence of amputations in IC patients was 0.4% (range 0.3%–0.5%) per year. Among CLI patients, the amputation rate during the first 6 months following revascularisation was 12.0% (95% CI 11.3–12.6). Thereafter, the incidence declined to approximately 2% per year. The cumulative combined incidence of death or amputation 3 years after revascularisation was 12.9% (95% CI 12.0–13.9) in IC patients and 48.8% (95% CI 47.7–49.8) in CLI patients. Among CLI patients, compared with IC patients, the prevalence of diabetes, ischaemic stroke, heart failure, and atrial fibrillation was approximately doubled and renal failure was nearly tripled, even after age standardisation. Conclusion The risk of amputation is particularly high during the first 6 months following revascularisation for CLI. IC patients have a benign course in terms of limb loss. Mortality in both IC and CLI patients is substantial. Revascularised CLI patients have different comorbidities from IC patients.

Purpose Ischaemic cerebrovascular accident (ICVA) is a common cause of morbidity and mortality. Identification of risk factors can reduce its incidence. We aim to estimate the incidence rate (IR) of hospitalised ICVA in the general population by sex and quantify its risk associated with several factors. Methods We followed up 907001 individuals aged 40–84years during a mean of 3.63years to ascertain the first episode of hospitalised ICVA between 2000 and 2004 using a UK primary care database. We evaluated the risk factors for ICVA through unconditional logistic regression (OR) with a nested case–control analysis, using 2953 incident cases and 10000 random controls frequency-matched by age, sex and year. Results The IR of hospitalised ICVA was 1.94 (95%CI: 1.87–2.01) per 1000 person-years in men and 1.59 (95%CI: 1.53–1.65) in women. The IR ratio adjusted by age was 1.35 (95%CI: 1.28–1.43). Major risk factors for the first ICVA were atrial fibrillation (AF) (OR of 1.96 (95%CI: 1.59–2.42) for men and 3.54 (95%CI: 2.85–4.39) for women), smoking, epilepsy and hypertension. AF patients on anticoagulant therapy presented a reduced risk of ICVA (OR: 0.39; 95%CI: 0.27–0.56) in both sexes. Hypertensive women that discontinued the treatment had an increased risk (OR: 2.53; 95%CI: 1.63–3.91). Conclusions Men had higher incidence of hospitalised ICVA than women. AF was the major risk factor for ICVA (more in women than men), followed by smoking. Among AF patients, those under anticoagulant therapy showed a significant reduced risk of first ICVA. Antihypertensive drug discontinuation increased the risk of ICVA among women. Copyright © 2011 John Wiley & Sons, Ltd. key words—cerebrovascular disease; epidemiology; risk factors; primary care

Background and Aim: Helicobacter pylori infection remains common in East Asia, though its prevalence is decreasing in Western countries. H. pylori-related atrophic gastritis (AG) may reduce the likelihood of gastroesophageal reflux disease (GERD). We investigated the prevalence of H. pylori infection and AG and their association with endoscopic findings and symptom-defined GERD in Shanghai. Methods: A representative random sample of 3600 Shanghai residents aged 18–80 years was invited to complete a general information questionnaire and a Chinese version of the Reflux Disease Questionnaire, to provide blood samples for H. pylori serology and pepsinogen (PG) I/II assay (to detect AG, defined as PGI

Background Population-based study of a random sample of 50-year-old men and women in Gothenburg, Sweden. Objective To examine the determinants of perceived health and the differences between 50-year-old men and women. Methods Men and women born in 1953 were examined between 2003 and 2004. Participation rate was 60% among the men and 67% among the women. Questionnaires were used, including one on perceived health that was ranked on a 7-point scale from 1 (excellent) to 7 (very poor). The participants' medical histories were obtained through a questionnaire, and risk factors were measured. Results Women generally perceived their health as poorer than men. Women experienced more symptoms than men, and most symptoms were more prevalent among women than men. Poor perceived health was strongly related to number of symptoms. In multivariable analyses 5 factors were related to perceived health in both men and women: working full or part time (women OR [odds ratio] = 0.3, men OR = 0.3) and physical activity (women OR = 0.6, men OR = 0.6) had a positive effect, whereas a low level of social activities (women OR = 1.9, men OR = 1.7), still feeling tired after normal hours of sleep (women OR = 4.5, men OR = 4.0), and feeling burned out during the past 12 months (women OR = 2.3, men OR = 3.0) had a negative effect on perceived health. Conclusions Women perceive their health as “worse” in comparison with men. Perceived health is a multifaceted condition related to social circumstances, physical activity, various symptoms, and tiredness after normal hours of sleep both in women and men.

Background— This study evaluated the risk of upper gastrointestinal bleeding (UGIB) associated with use of low-dose acetylsalicylic acid (ASA) alone and in combination with other gastrotoxic medications. Methods and Results— The Health Improvement Network UK primary care database was used to identify individuals 40 to 84 years of age with a UGIB diagnosis in 2000 to 2007 (n=2049). An age-, sex-, and calendar year-matched control group (n=20 000) was identified from the same source population. The relative risk (RR) of UGIB associated with use of low-dose ASA (75 to 300 mg/d), clopidogrel, and other commonly coadministered medications was estimated by multivariate logistic regression. The risk of UGIB was increased in current users of low-dose ASA (RR, 1.80; 95% confidence interval [CI], 1.59 to 2.03) or clopidogrel (RR, 1.67; 95% CI, 1.24 to 2.24) compared with nonusers. Compared with low-dose ASA monotherapy, the risk of UGIB was significantly increased when low-dose ASA was coadministered with clopidogrel (RR, 2.08; 95% CI, 1.34 to 3.21), oral anticoagulants (RR, 2.00; 95% CI, 1.15 to 3.45), low-/medium-dose nonsteroidal antiinflammatory drugs (RR, 2.63; 95% CI, 1.93 to 3.60), high-dose nonsteroidal antiinflammatory drugs (RR, 2.66; 95% CI, 1.88 to 3.76), or high-dose oral corticosteroids (RR, 4.43; 95% CI, 2.10 to 9.34); this was not apparent with coadministration of statins (RR, 0.99; 95% CI, 0.81 to 1.21) or low-dose oral corticosteroids (RR, 1.01; 95% CI, 0.58 to 1.77). Conclusions— Use of low-dose ASA is associated with an almost 2-fold increase in the risk of UGIB compared with nonuse. This risk is increased further in individuals taking low-dose ASA along with clopidogrel, oral anticoagulants, nonsteroidal antiinflammatory drugs, or high-dose oral corticosteroids.