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PURPOSE: To compare time to a composite endpoint of non-fatal acute myocardial infarction, non-fatal stroke or all-cause mortality in patients with type 2 diabetes mellitus who had their treatment intensified with a dipeptidylpeptidase-4 inhibitor or insulin following dual-therapy (metformin plus sulfonylurea) failure. METHODS: A retrospective cohort study was conducted on 5238 patients newly treated with either a dipeptidylpeptidase-4 inhibitor or insulin following dual-therapy failure (2007-2014). Data were sourced from UK General Practices. The risk of the composite outcome was compared between two treatment groups: metformin + sulfonylurea + insulin ( n = 1584) and metformin + sulfonylurea + dipeptidylpeptidase-4 inhibitor ( n = 3654), while adjusting for baseline covariates. Follow-up was for up to 5 years. Propensity score matching analysis and Cox proportional hazard models were employed. RESULTS: Overall, 123 and 171 composite outcome events occurred among patients who added insulin versus dipeptidylpeptidase-4 inhibitor, respectively (44.5 vs 14.6 events per 1000 person-years). Addition of insulin was associated with a significantly higher hazard ratio versus the addition of a dipeptidylpeptidase-4 inhibitor (adjusted hazard ratio = 2.6, 95% confidence interval: 1.9-3.4; p < 0.01), an effect that was more pronounced in obese (body mass index: 30-34.9 kg/m ) patients (corresponding adjusted hazard ratio 3.6, 95% confidence interval: 2.3-5.6; p < 0.01). CONCLUSION: In routine clinical practice, intensification of metformin + sulfonylurea therapy by adding insulin is associated with increased risk of cardiovascular events and death compared with adding a dipeptidylpeptidase-4 inhibitor. These findings are in line with suggestions from previous studies regarding the cardiovascular safety of insulin in type 2 diabetes mellitus, but should be interpreted with caution.

OBJECTIVE: To examine the UK practice patterns in treating newly diagnosed hypertension and to determine whether subgroups of high-risk patients are more or less likely to follow particular therapeutic protocols and to reach blood pressure goals. DESIGN: Retrospective cohort study. SETTING: This study examined adults in The Health Improvement Network (THIN) UK general practice medical records database who were initiated on medication for hypertension. PARTICIPANTS: 48 131 patients with essential hypertension diagnosed between 2008 and 2010 who were registered with a participating practice for a minimum of 13 months prior to, and 6 months following, initiation of therapy. We excluded patients with gestational hypertension or secondary hypertension. Patients were classified into risk groups based on blood pressure readings and comorbid conditions. PRIMARY AND SECONDARY OUTCOME MEASURES: Odds of receiving single versus fixed or free-drug combination therapy and odds of achieving blood pressure control were assessed using multivariable logistic regression. RESULTS: The vast majority of patients (95.8%) were initiated on single drug therapy. Patients with high cardiovascular risk (patients with grade 2-3 hypertension or those with high normal/grade 1 hypertension plus at least one cardiovascular condition pretreatment) had a statistically significant benefit of starting immediately on combination therapy when blood pressure control was the desired goal (OR: 1.23; 95% CI: 1.06 to 1.42) but, surprisingly, were less likely than patients with no risk factors to receive combination therapy (OR: 0.53; 95% CI: 0.47 to 0.59). CONCLUSIONS: Our results suggest that combination therapy may be indicated for patients with high cardiovascular risk, who accounted for 60.6% of our study population. The National Institute for Health and Care Excellence guideline CG34 of 2006 (in effect during the study period) recommended starting with single drug class therapy for most patients, and this advice does seem to have been followed even in cases where a more aggressive approach might have been considered.

OBJECTIVE: To evaluate the risk of serious adverse events among patients with type 2 diabetes mellitus initiating saxagliptin compared with oral antidiabetic drugs (OADs) in classes other than dipeptidyl peptidase-4 (DPP-4) inhibitors. RESEARCH DESIGN AND METHODS: Cohort studies using 2009-2014 data from two UK medical record data sources (Clinical Practice Research Datalink, The Health Improvement Network) and two USA claims-based data sources (HealthCore Integrated Research Database, Medicare). All eligible adult patients newly prescribed saxagliptin (n=110 740) and random samples of up to 10 matched initiators of non-DPP-4 inhibitor OADs within each data source were selected (n=913 384). Outcomes were hospitalized major adverse cardiovascular events (MACE), acute kidney injury (AKI), acute liver failure (ALF), infections, and severe hypersensitivity events, evaluated using diagnostic coding algorithms and medical records. Cox regression was used to determine HRs with 95% CIs for each outcome. Meta-analyses across data sources were performed for each outcome as feasible. RESULTS: There were no increased incidence rates or risk of MACE, AKI, ALF, infection, or severe hypersensitivity reactions among saxagliptin initiators compared with other OAD initiators within any data source. Meta-analyses demonstrated a reduced risk of hospitalization/death from MACE (HR 0.91, 95% CI 0.85 to 0.97) and no increased risk of hospitalization for infection (HR 0.97, 95% CI 0.93 to 1.02) or AKI (HR 0.99, 95% CI 0.88 to 1.11) associated with saxagliptin initiation. ALF and hypersensitivity events were too rare to permit meta-analysis. CONCLUSIONS: Saxagliptin initiation was not associated with increased risk of MACE, infection, AKI, ALF, or severe hypersensitivity reactions in clinical practice settings. TRIAL REGISTRATION NUMBER: NCT01086280, NCT01086293, NCT01086319, NCT01086306, and NCT01377935; Results.

OBJECTIVES: We studied oral glucocorticoids and osteonecrosis, a rare but serious bone disease, in individuals with various chronic inflammatory diseases. We hypothesised that we would find stronger associations in adults versus children and in people with autoimmune diseases. DESIGN: Retrospective cohort study. SETTING: Population-representative data (1994-2013) from general practices in the UK. PARTICIPANTS: Children and adults diagnosed with asthma; inflammatory bowel disease; juvenile, psoriatic or rheumatoid arthritis; psoriasis; or systemic lupus. EXPOSURES: Oral glucocorticoid patterns. PRIMARY AND SECONDARY OUTCOME MEASURES: Diagnosed osteonecrosis (primary) and osteonecrosis plus clinical features (eg, symptoms, pain medication, surgical repair) (secondary). Discrete time failure models estimated the adjusted hazard ratio (aHR) of incident osteonecrosis following oral glucocorticoid exposure. Hypothesis testing was one sided (with corresponding 90% CI) since glucocorticoids were unlikely protective. RESULTS: After adjusting for demographic, disease-related and health utilisation factors, glucocorticoid exposure was associated with osteonecrosis in adults (ages 18-49, aHR 2.1 (90% CI 1.5 to 2.9); ages ≥50, aHR 1.3 (90% CI 1.01 to 1.7)). However, low-dose glucocorticoids, corresponding to average doses <7.5 mg prednisolone daily and maximum doses <30 mg daily, were not associated with osteonecrosis in adults. Furthermore, even at high glucocorticoid doses, there was no evidence of increased osteonecrosis among glucocorticoid-exposed children (p=0.04 for interaction by age) (any glucocorticoid exposure, ages 2-9: aHR 1.1 (90% CI 0.7 to 1.7); ages 10-17: aHR 0.6 (90% CI 0.3 to 1.6)). Arthritis, inflammatory bowel disease and lupus were independently associated with osteonecrosis, but there was a similar dose relationship between glucocorticoids and osteonecrosis among adults with low-risk and high-risk diseases. CONCLUSIONS: Glucocorticoid use was clearly associated with osteonecrosis in a dose-related fashion in adults, especially young adults, but this risk was not detectable in children. The absolute risk of glucocorticoid-associated osteonecrosis in the general paediatric population and in adults taking low glucocorticoid doses is at most extremely small.

BACKGROUND & AIMS: Understanding the interactions between brain and gastrointestinal disorders requires analysis of the order of disease onset. We analyzed data from 2 independent studies to determine the proportion of individuals with diagnoses of functional gastrointestinal disorders (FGIDs) before diagnoses of mood or anxiety disorders (gut to brain), and vice versa (brain to gut). METHODS: We collected data from a retrospective study of 4966 patients diagnosed with a FGID (irritable bowel syndrome, dyspepsia, or constipation) and mood or anxiety disorder at general practices in the United Kingdom (health care seekers) over an average period of 13.1 years; we recorded which diagnosis appeared first and compared these with patients' sex and socioeconomic factors. We also collected data from a population study of 1002 randomly selected individuals in Australia (non-heath care seekers) followed from 1997 through 2009; we determined whether subjects were free of either FGID or an anxiety or mood disorder at baseline but developed either one after a 12-year follow-up period. RESULTS: Among the 4966 health care seekers, 3279 patients were diagnosed with a mood or anxiety disorder before an FGID (ratio of 2:1). This ratio increased with socioeconomic disadvantage. The time period between diagnosis of mood or anxiety disorder and FGID was longer (median, 3.5 years) than time period between diagnosis of an FGID and a mood or anxiety disorder (median, 1.8 years). Among non-heath care seekers (population study), equal proportions were diagnosed with a mood or anxiety disorder before versus after an FGID. CONCLUSIONS: In an analysis of data from a study of patients and a population-based study of individuals with these diagnoses, we found 2-fold more patients to receive a diagnosis of a mood or anxiety disorder before an FGID, but equal proportions of individuals in the population to be diagnosed with the mood or anxiety disorder before versus after an FGID. Among patients, the mood or anxiety disorder was on average diagnosed more than 3 years before the FGID, offering opportunity for prevention. Our findings support a role for adverse socioeconomic factors in development of FGIDs in patients with psychological disorders.

BACKGROUND: Reduction in cardiovascular death and hospitalization for heart failure (HHF) was recently reported with the sodium-glucose cotransporter-2 inhibitor (SGLT-2i) empagliflozin in patients with type 2 diabetes mellitus who have atherosclerotic cardiovascular disease. We compared HHF and death in patients newly initiated on any SGLT-2i versus other glucose-lowering drugs in 6 countries to determine if these benefits are seen in real-world practice and across SGLT-2i class. METHODS: Data were collected via medical claims, primary care/hospital records, and national registries from the United States, Norway, Denmark, Sweden, Germany, and the United Kingdom. Propensity score for SGLT-2i initiation was used to match treatment groups. Hazard ratios for HHF, death, and their combination were estimated by country and pooled to determine weighted effect size. Death data were not available for Germany. RESULTS: After propensity matching, there were 309 056 patients newly initiated on either SGLT-2i or other glucose-lowering drugs (154 528 patients in each treatment group). Canagliflozin, dapagliflozin, and empagliflozin accounted for 53%, 42%, and 5% of the total exposure time in the SGLT-2i class, respectively. Baseline characteristics were balanced between the 2 groups. There were 961 HHF cases during 190 164 person-years follow-up (incidence rate, 0.51/100 person-years). Of 215 622 patients in the United States, Norway, Denmark, Sweden, and the United Kingdom, death occurred in 1334 (incidence rate, 0.87/100 person-years), and HHF or death in 1983 (incidence rate, 1.38/100 person-years). Use of SGLT-2i, versus other glucose-lowering drugs, was associated with lower rates of HHF (hazard ratio, 0.61; 95% confidence interval, 0.51-0.73; <0.001); death (hazard ratio, 0.49; 95% confidence interval, 0.41-0.57; <0.001); and HHF or death (hazard ratio, 0.54; 95% confidence interval, 0.48-0.60; <0.001) with no significant heterogeneity by country. CONCLUSIONS: In this large multinational study, treatment with SGLT-2i versus other glucose-lowering drugs was associated with a lower risk of HHF and death, suggesting that the benefits seen with empagliflozin in a randomized trial may be a class effect applicable to a broad population of patients with type 2 diabetes mellitus in real-world practice. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02993614.

BACKGROUND: Studies investigating the risk factors for or causation of dementia must consider subjects prior to disease onset. To overcome the limitations of prospective studies and self-reported recall of information, the use of existing data is key. This review provides a narrative account of dementia ascertainment methods using sources of existing data. METHODS: The literature search was performed using: MEDLINE, EMBASE, PsychInfo and Web of Science. Included articles reported a UK-based study of dementia in which cases were ascertained using existing data. Existing data included that which was routinely collected and that which was collected for previous research. After removing duplicates, abstracts were screened and the remaining articles were included for full-text review. A quality tool was used to evaluate the description of the ascertainment methodology. RESULTS: Of the 3545 abstracts screened, 360 articles were selected for full-text review. 47 articles were included for final consideration. Data sources for ascertainment included: death records, national datasets, research databases and hospital records among others. 36 articles used existing data alone for ascertainment, of which 27 used only a single data source. The most frequently used source was a research database. Quality scores ranged from 7/16 to 16/16. Quality scores were better for articles with dementia ascertainment as an outcome. Some papers performed validation studies of dementia ascertainment and most indicated that observed rates of dementia were lower than expected. CONCLUSIONS: We identified a lack of consistency in dementia ascertainment methodology using existing data. With no data source identified as a "gold-standard", we suggest the use of multiple sources. Where possible, studies should access records with evidence to confirm the diagnosis. Studies should also calculate the dementia ascertainment rate for the population being studied to enable a comparison with an expected rate.

AIMS: To investigate the probability of developing type 2 diabetes mellitus (T2DM) at different body mass index levels compared to matched non-diabetic controls in a multi-ethnic population. MATERIALS AND METHODS: This was a case-control study of 90 367 patients with incident diabetes and 362 548 age-sex-ethnicity matched controls from UK primary care. The probability of developing T2DM was estimated. RESULTS: Case and control patients were 56 years old at index and 56% were male. Patients with T2DM had significantly higher mean BMI levels by about 5 kg/m at diagnosis (32.2 kg/m ) compared to the matched controls (27.4 kg/m ). White Europeans (n = 79 270), African-Caribbeans (n = 4115) and South Asians (n = 7252) were 58, 48 and 46 years old with a mean BMI of 32.5, 31.1 and 29.2 kg/m , respectively, at diagnosis. More South Asians developed T2DM at BMI below 30 kg/m (38%) than White Europeans (26%) and African-Caribbeans (29%) (all P  < .01). Within the 18 to 70-year age range, South Asian males and females had a significantly higher probability of developing diabetes in the continuously measured BMI range of 18 to 30 kg/m , compared to White Europeans and African-Caribbeans. Across all age groups <70 years, South Asians and African-Caribbeans had a significantly higher probability of developing T2DM in the normal weight and overweight categories, compared to White Europeans. However, this risk pattern of developing diabetes was reversed amongst the obese in all age groups. CONCLUSION: Risk patterns of developing diabetes at different levels of obesity varies among ethnic groups across all ages, while South Asians and African-Caribbeans carry the highest risk at a younger age and at lower adiposity burden.

The 72nd Annual Meeting of The Canadian Rheumatology Association (CRA) was held at The Westin Ottawa, Ottawa, Ontario, Canada, February 8-11, 2017. The program consisted of presentations covering original research, symposia, awards, and lectures. Highlights of the meeting include the following 2017 award winners: Dr. Vinod Chandran, Young Investigator; Dr. Jacques P. Brown, Distinguished Investigator; Dr. David Robinson, Teacher-Educator; Dr. Michel Zummer, Distinguished Rheumatologist; Ms. Rebecca Gole, Best Abstract on SLE Research by a Trainee - Ian Watson Award; Ms. Bailey Russell, Best Abstract on Clinical or Epidemiology Research by a Trainee - Phil Rosen Award; Dr. Sahil Koppikar and Dr. Henry Averns, Practice Reflection Award; Dr. Shirine Usmani, Best Abstract on Basic Science Research by a Trainee; Ms. Carol Dou, Best Abstract for Research by an Undergraduate Student; Dr. Dania Basodan, Best Abstract on Research by a Rheumatology Resident; Dr. Claire Barber, Best Abstract on Adult Research by Young Faculty; Ms. Audrea Chen, Best Abstract by a Medical Student; Dr. Kun Huang, Best Abstract by a Post-Graduate Resident; and Dr. Ryan Lewinson, Best Abstract by a Post-Graduate Research Trainee. Lectures and other events included a Keynote Lecture by Jonathon Fowles: Exercise is Medicine: Is Exercise a Good or Bad Thing for People with Arthritis?; State of the Art Lecture by Matthew Warman: Insights into Bone Biology and Therapeutics Gleaned from the Sustained Investigation of Rare Diseases; Dunlop-Dottridge Lecture by Allen Steere: Lyme Disease: A New Problem for Rheumatologists in Canada; and the Great Debate: Be it Resolved that the Least Expensive Treatment Should be Chosen. Switch, Switch, Switch! Arguing for: Jonathan Chan and Antonio Avina, and against: Marinka Twilt and Glen Hazlewood. Topics such as rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjögren syndrome, psoriatic arthritis, spondyloarthritis, vasculitis, osteoarthritis, fibromyalgia, pediatric rheumatology, and their respective diagnoses, treatments, and outcomes are reflected in the abstracts, which we are pleased to publish in this issue of .

OBJECTIVE: To estimate the patterns of care and related resource use attributable to managing acute and chronic wounds among a catchment population of a typical clinical commissioning group (CCG)/health board and corresponding National Health Service (NHS) costs in the UK. METHOD: This was a sub-analysis of a retrospective cohort analysis of the records of 2000 patients in The Health Improvement Network (THIN) database. Patients' characteristics, wound-related health outcomes and health-care resource use were quantified for an average CCG/health board with a catchment population of 250,000 adults ≥18 years of age, and the corresponding NHS cost of patient management was estimated at 2013/2014 prices. RESULTS: An average CCG/health board was estimated to be managing 11,200 wounds in 2012/2013. Of these, 40% were considered to be acute wounds, 48% chronic and 12% lacking any specific diagnosis. The prevalence of acute, chronic and unspecified wounds was estimated to be growing at the rate of 9%, 12% and 13% per annum respectively. Our analysis indicated that the current rate of wound healing must increase by an average of at least 1% per annum across all wound types in order to slow down the increasing prevalence. Otherwise, an average CCG/health board is predicted to manage ~23,200 wounds per annum by 2019/2020 and is predicted to spend a discounted (the process of determining the present value of a payment that is to be received in the future) £50 million on managing these wounds and associated comorbidities. CONCLUSION: Real-world evidence highlights the substantial burden that acute and chronic wounds impose on an average CCG/health board. Strategies are required to improve the accuracy of diagnosis and healing rates.

AIM: To identify risk factors associated with the development of DMO among patients diagnosed with type 2 diabetes managed in a primary care setting in the UK. METHODS: A case-control study nested in a cohort of incident Type 2 diabetes identified in The Health Improvement Network database from 2000-2007. Cases were people with DMO (N=211) and controls were a DMO-free sample (N=2194). No age restrictions were applied. Adjusted odds ratios and 95%CIs were estimated (OR; 95%CI). RESULTS: DMO increased with high alcohol use (2.88; 1.49-5.55), cataracts (4.10; 2.73-6.15), HbA1c ≥7% (1.58; 1.08-2.32), systolic blood pressure ≥160mm Hg (2.03; 1.17-3.53), total cholesterol ≥5mmol/L (1.66; 1.15-2.39), LDL ≥3mmol/L (1.73; 1.14-2.61), and microalbuminuria (1.78; 1.16-2.73). Diuretic drugs were associated with a reduced risk of DMO (0.68; 0.47-0.99), as did smoking (0.47; 0.28-0.77), overweight (0.53; 0.30-0.96) or obesity (0.52; 0.30-0.91) at diabetes diagnosis, and high triglyceride levels (0.51; 0.35-0.74). Patients treated with anti-diabetic drugs showed higher risk of DMO than non-treated patients, particularly those with sulphonylureas (3.40; 2.42-4.78), insulin (3.21; 1.92-5.36) or glitazones (1.88; 1.17-3.04). CONCLUSION: In patients with type 2 diabetes managed in primary care, multiple factors associated with DMO were identified, such as cataracts, microalbuminuria and high levels of HbA1c, systolic BP, total cholesterol, and LDL. Diuretic drugs were associated with a reduced risk of DMO. Treated diabetes, particularly with sulphonylureas, insulin or glitazones showed highest risk of DMO. The inverse association between smoking, obesity, and triglycerides and DMO deserves further research.

OBJECTIVES: Alterations in the immune system and infections are suspected to increase susceptibility to giant cell arteritis (GCA). Recently herpes zoster has been directly implicated in the pathogenesis of GCA. We examined the association between prior infections, in particular herpes zoster, and incident GCA in a population-based cohort. METHODS: A nested case-control study was performed using an electronic database from the UK. Cases with newly diagnosed GCA were identified using a validated algorithm and compared with age-matched, sex-matched and practice-matched controls. Conditional logistic regression was used to examine the relationship between any infection or herpes zoster infection on the development of GCA after adjusting for potential confounders; results were expressed as incidence rate ratios (IRRs). RESULTS: There were 4559 cases of GCA and 22 795 controls. Any prior infection and herpes zoster were associated with incident GCA (IRR 1.26 (95% CI 1.16 to 1.36), p<0.01; and 1.17 (95% CI 1.04 to 1.32), p<0.01, respectively). A greater number of infections was associated with a higher risk of developing GCA (IRR for 1, 2-4 and ≥5 infections was 1.28, 1.60 and 2.18, respectively). CONCLUSIONS: Antecedent infections and, to a lesser extent, herpes zoster infections are modestly associated with incident GCA. These data provide population-level support for the hypothesis that long-standing alterations of the immune system are associated with susceptibility to GCA and suggest that herpes zoster is unlikely to play a major causal role in the pathogenesis of GCA.

Essentials Intracranial bleeds (ICB) are serious clinical events that have been associated with aspirin use. Incidence rates of ICB were calculated among new-users of low-dose aspirin in the UK (2000-2012). Over a median follow-up of 5.58 years, the incidence of ICB was 0.08 per 100 person-years. Our estimates are valuable for inclusion in risk-benefit assessments of low-dose aspirin use. SUMMARY: Background Low-dose aspirin protects against both ischemic cardiovascular (CV) events and colorectal cancer (CRC). However, low-dose aspirin may be associated with a slightly increased risk of intracranial bleeds (ICBs). Objectives To obtain the incidence rates of ICBs overall and by patient subgroups among new users of low-dose aspirin. Patients/Methods Using The Health Improvement Network (THIN) UK primary-care database (2000-2012), we identified a cohort of new users of low-dose aspirin aged 40-84 years (N = 199 079; mean age at start of follow-up, 63.9 years) and followed them for up to 14 years (median 5.58 years). Incident ICB cases were identified and validated through linkage to hospitalization data and/or review of THIN records with free-text comments. Incidence rates with 95% confidence intervals (CIs) were calculated. Results Eight hundred and eighty-one incident ICBs cases were identified: 407 cases of intracerebral hemorrhage (ICH), 283 cases of subdural hematoma (SDH), and 191 cases of subarachnoid hemorrhage (SAH). Incidence rates per 100 person-years were 0.08 (95% CI 0.07-0.08) for all ICBs, 0.04 (95% CI 0.03-0.04) for ICH, 0.03 (95% CI 0.02-0.03) for SDH, and 0.02 (95% CI 0.01-0.02) for SAH. The ICB incidence rates per 100 person-years for individuals with an indication of primary CV disease prevention were 0.07 (95% CI 0.06-0.07) and 0.09 (95% CI 0.08-0.10) for secondary CV disease prevention. Incidence rates were higher in men for SDH, and higher in women for ICH and SAH. Conclusions Our results provide valuable estimates of the absolute ICB risk for incorporation into risk-benefit assessments of low-dose aspirin use.

PURPOSE: To describe the characteristics of new users of cilostazol in Europe with the aim to support the evaluation of its benefit/risk as used in regular clinical practice before the implementation of labeling changes recommended by the European Medicines Agency. METHODS: New users of cilostazol were identified in populations enrolled in five European health automated databases in the UK (The Health Improvement Network [THIN]), Spain (EpiChron cohort and Information System for the Improvement of Research in Primary Care [SIDIAP]), Sweden (National Registers), and Germany (German Pharmacoepidemiological Research Database [GePaRD]) between 2002 and 2012. New users were characterized according to the prevalence of cardiovascular disease and other comorbidities, concurrent use of interacting medications, new contraindications, duration of use, and potential off-label prescribing. RESULTS: We identified 22 593 new users of cilostazol. The median age was between 68.0 (THIN) and 73.7 (Sweden) years. More than 78% of users had concomitant cardiovascular disease, and between 78.8% (GePaRD) and 91.6% (THIN) were treated with interacting medications. Prevalence of new cardiovascular contraindications ranged from 1.5% (THIN) to 11.6% (GePaRD), and concurrent use of two or more antiplatelet drugs ranged from 6.3% (SIDIAP) to 13.5% (EpiChron cohort). Between 39.4% (Sweden) and 52.9% (THIN) of users discontinued cilostazol in the first 3 months. Between 41.0% (SIDIAP) and 93.4% (THIN) were considered to have received cilostazol according to the European Medicines Agency labeling. CONCLUSIONS: In this collaborative European study, most cilostazol users were elderly patients with a high prevalence of cardiovascular diseases and other comorbidity and concurrent use of interacting drugs, indicating that this is a vulnerable population at high risk of complications, especially cardiovascular events. © 2017 The Authors. Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd.

OBJECTIVE: The objective of this study was to examine cause-specific mortality in patients with PsA compared with the general population and compared with patients with RA. METHODS: A cohort study was performed using The Health Improvement Network among patients aged 18-89 years with data from 1994 to 2010. PsA and RA were defined by medical codes, and up to 10 unexposed controls were matched on practice and start date within the practice. Cause of death was classified using categories from UK death statistics. Each death was manually reviewed to ensure appropriate classification. Age- and sex-adjusted hazard ratios (HRs) and multivariable adjusted HRs were calculated using competing risks survival regression. RESULTS: Among patients with PsA (8706), RA (41 752) and unexposed controls (81 573), 470, 7004 and 5269 deaths were observed, respectively. The most common causes of death among all patients were cardiovascular disease, followed by malignancy, respiratory deaths and infection. Cause of death was unknown in ∼25%. Among PsA patients, cardiovascular (1.09, 0.91-1.32), respiratory (0.97, 0.79-1.20), malignancy (1.03, 0.86-1.25) and infection deaths (1.05, 0.79-1.39) were not elevated. Among patients with RA, cardiovascular (1.55, 1.44-1.66), respiratory (1.85, 1.72-2.01), malignancy (1.18, 1.08-1.28) and infection deaths (2.21, 2.00-2.44) were significantly elevated compared with population controls. Although less common, suicide deaths were elevated in PsA and RA (HR 3.03 and 2.47, respectively). CONCLUSION: Overall mortality and cause-specific mortality risk were not elevated among patients with PsA except for suicide deaths. Patients with RA were at increased risk of deaths from cardiovascular, respiratory, cancer and infectious diseases.

BACKGROUND: Reducing inappropriate antibiotic prescribing in primary care is a public health priority. OBJECTIVES: We hypothesized that a subset of patients account for the majority of antibiotic prescriptions in primary care. We investigated the relationship between the total amount of antibiotics prescribed, individual-level antibiotic use and comorbidity. METHODS: This was a cohort study using electronic health records from 1 948 390 adults registered with 385 primary care practices in the UK in 2011-13. We estimated the average number of antibiotic prescriptions per patient and the association between prescribing and comorbidity. We modelled the impact on total prescribing of reducing antibiotic use in those prescribed antibiotics most frequently. RESULTS: On average 30.1% (586 194/1 948 390) of patients were prescribed at least one antibiotic per year. Nine percent (174 602/1 948 390) of patients were prescribed 53% (2 091 496/3 922 732) of the total amount of antibiotics, each of whom received at least five antibiotic prescriptions over 3 years. The presence of any comorbidity increased the prescribing rate by 44% [adjusted incidence rate ratio (IRR) 1.44, 95% CI 1.43-1.45]; rates of prescribing to women exceeded those in men by 62% (adjusted IRR 1.62, 95% CI 1.62-1.63). CONCLUSIONS: Half of antibiotics prescribed to adults in primary care were for <10% of patients. Efforts to tackle antimicrobial resistance should consider the impact of this on total prescribing.

AIM: The glucagon-like peptide-1 receptor agonist (GLP1a) liraglutide has been described to benefit patients with type 2 diabetes mellitus (T2DM) at high cardiovascular risk. However, there are still uncertainties relating to these cardiovascular benefits: whether they also apply to an unselected diabetic population that includes low-risk patients, represent a class-effect, and could be observed in a real-world setting. METHODS: We conducted a population-based, retrospective open cohort study using data derived from The Health Improvement Network database between Jan 2008 to Sept 2015. Patients with T2DM exposed to GLP1a (n=8345) were compared to age, gender, body mass index, duration of T2DM and smoking status-matched patients with T2DM unexposed to GLP1a (n=16,541). RESULTS: Patients with diabetes receiving GLP1a were significantly less likely to die from any cause compared to matched control patients with diabetes (adjusted incidence rate ratio [aIRR]: 0.64, 95% CI: 0.56-0.74, P-value<0.0001). Similar findings were observed in low-risk patients (aIRR: 0.64, 95% CI: 0.53-0.76, P -value=0.0001). No significant difference in the risk of incident CVD was detected in the low-risk patients (aIRR: 0.93, 95% CI: 0.83-1.12). Subgroup analyses suggested that effect is persistent in the elderly or across glycated haemoglobin categories. CONCLUSIONS: GLP1a treatment in a real-world setting may confer additional mortality benefit in patients with T2DM irrespective of their baseline CVD risk, age or baseline glycated haemoglobin and was sustained over the observation period.