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The aim of present study was to investigate the risk of heart failure associated with dopamine agonist use in patients with Parkinson's disease. The data sources of this study were four different population-based, healthcare databases in United Kingdom, Italy and Netherlands. A case control study nested within a cohort of Parkinson's disease patients who were new users of either dopamine agonist or levodopa was conducted. Incident cases of heart failure were identified and validated, using Framingham criteria. Controls were matched to cases on age, gender and database. To estimate the risk of newly diagnosed heart failure with ergot and non-ergot derived dopamine agonists, as compared to levodopa, odds ratios and 95% confidence intervals were calculated through conditional logistic regression. In the cohort of 25,459 Parkinson's disease patients (11,151 new users of dopamine agonists, 14,308 new users of levodopa), 518 incident heart failure cases were identified during follow-up. Compared to levodopa, no increased risk of heart failure was found for ergot dopamine agonists (odds ratio: 1.03; 95% confidence interval: 0.69-1.55). Among non-ergot dopamine agonists, only pramipexole was associated with an increased risk of heart failure (odds ratio: 1.61; 95%confidence interval: 1.09-2.38), especially in the first three months of therapy (odds ratio: 3.06; 95% confidence interval: 1.74-5.39) and in patients aged 80 years and older (odds ratio: 3.30; 95% confidence interval: 1.62-7.13). The results of this study indicate that ergot dopamine agonist use in Parkinson's disease patients was not associated with an increased risk of newly diagnosed heart failure. Among non-ergot dopamine agonists, we observed a statistically significant association between pramipexole use and heart failure, especially during the first months of therapy and in very old patients.

BACKGROUND: In 2003, the Committee on Safety of Medicines (CSM) advised against treatment with selective serotonin reuptake inhibitors (SSRIs) other than fluoxetine in children, due to a possible increased risk of suicidal behaviour. This study examined the effects of this safety warning on general practitioners' depression diagnosing and prescription behaviour in children. METHODS AND FINDINGS: We identified a cohort of 1,502,753 children (<18 y; registered with GP for >6 m) in The Health Improvement Network (THIN) UK primary care database. Trends in incidence of depression diagnoses, symptoms and antidepressant prescribing were examined 1995-2009, accounting for deprivation, age and gender. We used segmented regression analysis to assess changes in prescription rates. Overall, 45,723 (3%) children had ≥ 1 depression-related entry in their clinical records. SSRIs were prescribed to 16,925 (1%) of children. SSRI prescription rates decreased from 3.2 (95%CI:3.0,3.3) per 1,000 person-years at risk (PYAR) in 2002 to 1.7 (95%CI:1.7,1.8) per 1,000 PYAR in 2005, but have since risen to 2.7 (95%CI:2.6,2.8) per 1,000 PYAR in 2009. Prescription rates for CSM-contraindicated SSRIs citalopram, sertraline and especially paroxetine dropped dramatically after 2002, while rates for fluoxetine and amitriptyline remained stable. After 2005 rates for all antidepressants, except paroxetine and imipramine, started to rise again. Rates for depression diagnoses dropped from 3.0 (95%CI:2.8,3.1) per 1,000 PYAR in 2002 to 2.0 (95%CI:1.9,2.1) per 1,000 PYAR in 2005 and have been stable since. Recording of symptoms saw a steady increase from 1.0 (95%CI:0.8,1.2) per 1,000 PYAR in 1995 to 4.7 (95%CI:4.5,4.8) per 1,000 PYAR in 2009. CONCLUSIONS: The rates of depression diagnoses and SSRI prescriptions showed a significant drop around the time of the CSM advice, which was not present in the recording of symptoms. This could indicate caution on the part of GPs in making depression diagnoses and prescribing antidepressants following the CSM advice.

The national cost of managing genital warts (GWs) in the UK has not been fully estimated, yet is required to inform decisions on vaccination against human papillomavirus. This study estimated the 2010 UK costs based on secondary genitourinary (GU) medicine clinic data from the Health Protection Agency (HPA) and primary care data from the Health Improvement Network database. Extrapolating data to 2010 resulted in 173,077 GU medicine clinic and 16,782 primary care GW episodes. Using treatment patterns obtained from key opinion leaders and tariffs from National Health Service Payment by Results (NHS PbR), the national costs were estimated at £52.4 million: £276 per treated GW episode.

Increasing epidemiological evidence suggests independent associations between psoriasis and cardiovascular and metabolic disease. Our objective was to test the hypothesis that directly assessed psoriasis severity relates to the prevalence of metabolic syndrome and its components. A population-based, cross-sectional study was undertaken using computerized medical records from the Health Improvement Network Study population including individuals in the age group of 45-65 years with psoriasis and practice-matched controls. The diagnosis and extent of psoriasis were determined using provider-based questionnaires. Metabolic syndrome was defined using the National Cholesterol Education Program Adult Treatment Panel III criteria. A total of 44,715 individuals were included: 4,065 with psoriasis and 40,650 controls. In all, 2,044 participants had mild psoriasis (2% body surface area (BSA)), 1,377 had moderate psoriasis (3-10% BSA), and 475 had severe psoriasis (>10% BSA). Psoriasis was associated with metabolic syndrome, adjusted odds ratio (adj. OR 1.41, 95% confidence interval (CI) 1.31-1.51), varying in a "dose-response" manner, from mild (adj. OR 1.22, 95% CI 1.11-1.35) to severe psoriasis (adj. OR 1.98, 95% CI 1.62-2.43). Psoriasis is associated with metabolic syndrome and the association increases with increasing disease severity. Furthermore, associations with obesity, hypertriglyceridemia, and hyperglycemia increase with increasing disease severity independently of other metabolic syndrome components. These findings suggest that screening for metabolic disease should be considered for psoriasis, especially when it is severe.

PURPOSE: In type 2 diabetes, the optimal stage to introduce insulin can be unclear. We compared the incidence of subsequent vascular disease between treatment regimens, that is, adding another oral glucose-lowering drug (OGLD) versus starting insulin treatment. METHODS: People with poor control on OGLDs who intensified treatment (2000-2007) were grouped by number of baseline OGLDs. Two composite endpoints, of macrovascular disease (all-cause mortality, myocardial infarction, acute coronary syndrome and stroke) and of microvascular disease (peripheral neuropathy, nephropathy or retinopathy), together with HbA(1c) and weight change over a year, were compared in those beginning insulin versus an additional OGLD. All data came from The Health Information Network UK primary care database. RESULTS: After exclusions, 14,904 people intensified treatment from one OGLD, 7231 from two and 978 from three, 9, 41 and 90%, respectively, started insulin. Average follow-up was 3.5 years. The adjusted hazard ratios for macrovascular events, OGLD versus insulin, were 0.53 (95%CI 0.42, 0.69) from one baseline treatment, 0.85 (0.70 1.04) from two and 1.07 (0.50, 2.30) from three, with no difference in risk of microvascular disease in any comparison. Mean body weight increased, and mean HbA(1c) fell across groups; the only significant adjusted comparison was greater weight increase when commencing insulin from one OGLD. CONCLUSIONS: Starting insulin rather than adding another OGLD to double or triple oral therapy did not significantly increase the incidence of vascular events. Beginning insulin from one OGLD was uncommon. More incident macrovascular disease in this group may be caused by residual confounding.

BACKGROUND: Discontinuation of low-dose acetylsalicylic acid (ASA) leads to an increased risk of cardiovascular and cerebrovascular events in patients taking low-dose ASA for secondary cardiovascular prevention. However, little is known about the rate of discontinuation in everyday clinical practice. OBJECTIVES: To assess the rate of low-dose ASA discontinuation in primary care, and identify factors that predict discontinuation. METHODS: The Health Improvement Network, a large UK primary care database, was used to identify patients aged 50-84 years who received at least two consecutive prescriptions for low-dose ASA for secondary cardiovascular or cerebrovascular prevention in 2000-2007 (n = 35,639). Discontinuation was defined as a period of at least 90 days after completion of the last prescribed course of ASA during which no repeat prescription was issued. RESULTS: During the study, 11,729 patients (32.9%) discontinued ASA therapy (mean follow-up 2.5 years). The discontinuation rate was lower in patients with ASA indicated for myocardial infarction than for other indications. The diagnosis of gastrointestinal disorders during the study (overall odds ratio: 1.74; 95% confidence interval: 1.61-1.88) was associated with increased rates of ASA discontinuation, whereas co-prescription of a proton pump inhibitor from the start of ASA therapy was associated with a decreased rate of discontinuation (odds ratio: 0.80; 95% confidence interval: 0.75-0.86). Co-prescription of several other cardioprotective medications was also associated with a reduced risk of discontinuation, as were increasing age, prior hospitalization and overall number of co-medications. CONCLUSION: Continuous co-prescription of a PPI with low-dose ASA may improve adherence and outcomes, particularly in patients at both cardiovascular and gastrointestinal risk.

BACKGROUND: Clinical characteristics and patterns of healthcare utilization in patients with painful neuropathic disorders (PNDs) who are under the care of general practitioners (GPs) in the UK are not well understood. METHODS: Using a large electronic UK database, we identified all adults (age ≥ 18 years) with any GP encounters between 1 January 2006-31 December 2006 at which a diagnosis of PND was noted ("PND patients"). An age-and gender-matched comparison group also was constituted consisting of randomly selected patients with one or more GP encounters-but no mention of PNDs-during this period. Characteristics and patterns of healthcare utilization of patients in the two groups were then examined over the one-year study period. RESULTS: The study sample consisted of 31,688 patients with mention of PNDs and an equal number of matched comparators; mean age was 56 years, and 62% were women. The prevalence of various comorbidities was higher among patients in the PND group, including digestive disorders (31% vs. 17% for comparison group), circulatory disorders (29% vs. 22%), and depression (4% vs. 3%) (all p < 0.01). Receipt of prescriptions for pain-related pharmacotherapy also was higher among PND patients, including nonsteroidal anti-inflammatory drugs (56% of PND patients had one or more such prescriptions vs. only 22% in the comparison group), opioids (49% vs. 12%), tricyclic antidepressants (20% vs. 1%), and antiepileptics (12% vs. 1%) (all p < 0.01). PND patients also averaged significantly more GP visits (22.8 vs. 14.2) and referrals to specialists (2.8 vs. 1.4) over one year (both comparisons p < 0.01). CONCLUSIONS: Patients with PNDs under the care of GPs in the UK have relatively high levels of use of healthcare services and pain-related pharmacotherapy.

At the 2010 annual meeting of GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis), 24 trainees (rheumatology fellows and dermatology residents) engaged in research in psoriatic disease were invited to present their work at the Trainees Symposium, which preceded the GRAPPA meeting and was also attended by GRAPPA members and invited guests. Nineteen posters and 6 oral presentations were presented by the trainees, all of which are summarized here.

PURPOSE: There is little information regarding antipsychotic prescription in primary care, despite general practitioners issuing most ongoing prescriptions. We sought to investigate changes in oral antipsychotic prescriptions in primary care from January 1998 to December 2007. METHODS: We conducted a cohort analysis of patients diagnosed with schizophrenia in primary care in the United Kingdom, using The Health Improvement Network database, to determine the proportions of prescribed antipsychotics. We investigated the yearly estimates of the overall time patients spent in treatment with any antipsychotic as well as the class of antipsychotic and individual antipsychotic agent. RESULTS: We found that in any one calendar year, approximately 24% of patients previously prescribed antipsychotics do not receive treatment in primary care. Over the last decade, people with schizophrenia have been prescribed antipsychotic treatment for greater proportions of time. The greatest increase was observed in older women. The overall increase in treatment time can be attributed to the increased prescription of second-generation antipsychotics (SGAs). The annual proportion of time in SGA treatment increased from 16.6% to 51.2% within the study period, whereas time in first-generation antipsychotic treatment reduced from 37.1% to 15.0%. Overall, olanzapine, risperidone and sulpiride were prescribed for the longest periods of time. CONCLUSIONS: Over the last decade, the general practice of prescribing SGAs has increased whereas first-generation antipsychotic prescriptions have declined. By 2007, patients with schizophrenia were prescribed antipsychotics for greater proportions of time, perhaps reflecting the greater acceptability of SGAs or a shift from secondary to primary care prescription.

BACKGROUND: Influenza vaccination is recommended for older people irrespective of cognitive decline or residential setting. OBJECTIVE: To examine the effect of dementia diagnosis on flu vaccination uptake in community and care home residents in England and Wales. METHODS: Retrospective analysis of a primary care database with 378,462 community and 9,106 care (nursing and residential) home residents aged 65-104 in 2008-09. Predictors of vaccine uptake were examined adjusted for age, sex, area deprivation and major chronic diseases. RESULTS: Age and sex standardised uptake of influenza vaccine was 74.7% (95% CI: 73.7-75.8%) in community patients without dementia, 71.4% (69.3-73.5%) in community patients with dementia, 80.5% (78.9-82.2%) in care home patients without dementia and 83.3% (81.4-85.3%) in care home patients with dementia. In a fully adjusted model, compared with community patients without dementia, patients with dementia in the community were less likely to receive vaccination (RR: 0.96, 95% CI: 0.94-0.97) while care home patients with (RR: 1.06, 1.03-1.09) and without (RR: 1.03, 1.01-1.05) dementia were more likely to receive vaccination. Area deprivation and chronic diseases were, respectively, negative and positive predictors of uptake. CONCLUSION: Lower influenza vaccine uptake among community patients with dementia, compared with care home residents, suggests organisational barriers to community uptake but high uptake among patients with dementia in care homes does not suggest concern over informed consent acts as a barrier. Primary care for community patients with dementia needs to ensure that they receive all appropriate preventive interventions.

OBJECTIVE: To determine the independent associations of antihypertensive drugs with the risk of incident gout among people with hypertension. DESIGN: Nested case-control study. SETTING: UK general practice database, 2000-7. PARTICIPANTS: All incident cases of gout (n = 24,768) among adults aged 20-79 and a random sample of 50,000 matched controls. MAIN OUTCOME MEASURE: Relative risk of incident gout associated with use of antihypertensive drugs. RESULTS: After adjusting for age, sex, body mass index, visits to the general practitioner, alcohol intake, and pertinent drugs and comorbidities, the multivariate relative risks of incident gout associated with current use of antihypertensive drugs among those with hypertension (n = 29,138) were 0.87 (95% confidence interval 0.82 to 0.93) for calcium channel blockers, 0.81 (0.70 to 0.94) for losartan, 2.36 (2.21 to 2.52) for diuretics, 1.48 (1.40 to 1.57) for β blockers, 1.24 (1.17 to 1.32) for angiotensin converting enzyme inhibitors, and 1.29 (1.16 to 1.43) for non-losartan angiotensin II receptor blockers. Similar results were obtained among those without hypertension. The multivariate relative risks for the duration of use of calcium channel blockers among those with hypertension were 1.02 for less than one year, 0.88 for 1-1.9 years, and 0.75 for two or more years and for use of losartan they were 0.98, 0.87, and 0.71, respectively (both P<0.05 for trend). CONCLUSIONS: Compatible with their urate lowering properties, calcium channel blockers and losartan are associated with a lower risk of incident gout among people with hypertension. By contrast, diuretics, β blockers, angiotensin converting enzyme inhibitors, and non-losartan angiotensin II receptor blockers are associated with an increased risk of gout.

OBJECTIVE: To compare the prevalence and predictors of antidepressant prescribing in older care home and community residents in England and Wales. DESIGN: Retrospective analysis of primary care consultation and antidepressant prescribing data. SETTING: The setting included 326 general (family) practices in England and Wales supplying data to The Health Improvement Network database between 2008 and 2009. PARTICIPANTS: Participants were 10,387 care home and 403,259 community residents aged 65 to 104. MAIN OUTCOME MEASURE: Antidepressant prescription in the last 3 months of recorded data for each patient. RESULTS: Prevalence rates for antidepressant prescribing were 10.3% (95% confidence interval 10%-10.6%) for community and 37.5% (36.2%-38.9%) for care home residents. After excluding low-dose tricyclics (often used for other indications) prevalences were 7.3% (7.1%-7.5%) and 33.6% (32.3%-34.9%) respectively; of these, 21.7% (20.8%-22.6%) of community and 4.8% (3.9%-5.6%) of care home prescriptions were for antidepressants advised as best avoided in this age group. After indirect standardization for age, sex, and chronic disease prevalence, the ratio for prescribing was 2.4 (2.3-2.5) in care homes compared with the community; 28.3% (26.6%-30.1%) of community and 42.5% (39.4%-45.7%) of care home residents prescribed antidepressants had no appropriate recorded indication. CONCLUSIONS: This national sample confirms the high prevalence of antidepressant prescribing to older people, particularly in care homes, frequently without a documented indication. The strong association found between chronic disease and antidepressant prescribing did not explain the higher care home prescribing rate. Widespread community use of nonrecommended antidepressants is also a concern.

AIMS: We investigated whether differences in duration of first insulin use in type 2 diabetes remain after adjustment for potential confounders, and what factors are associated with longer use. METHODS: People prescribed a first insulin (2000-2007) after 2-3 non-insulin glucose lowering treatments (OGLD) were identified from the THIN UK primary care database and grouped by insulin, detemir (n=165), glargine (n=1011) or NPH (n=420). Time from beginning insulin to the prescription of another insulin type or a glucagon-like peptide was compared between insulins in a Cox model adjusting for: demographics, HbA1c, history of vascular complications and cardiovascular risk factors. The strength of association between duration of use and these variables was investigated. RESULTS: The adjusted hazard ratios compared to glargine for treatment change were 1.58 (95% CI 1.25, 2.00) for detemir and 1.49 (1.25, 1.78) for NPH. Lower mean treatment HbA(1c) correlated with longer time to a different insulin regimen (Spearman rank correlation -0.30, p<0.01) as were continuing OGLDs, older age, longer time from diagnosis, lower body mass index, lower HbA(1c), and no heart failure at baseline. CONCLUSIONS: People who began treatment with glargine and those with better on-treatment HbA(1c) remained on their first insulin for longer than those who began detemir or NPH.

OBJECTIVES: To determine changes in prescribing patterns in primary care of antipsychotic and mood stabiliser medication in a representative sample of patients with bipolar disorder in the United Kingdom over a fifteen year period and association with socio-demographic factors. METHODS: We identified 4700 patients in the Health Improvement Network (THIN) primary care database, who had received treatment for bipolar disorder between 1995 and 2009. The proportion of time for which each individual was prescribed a particular medication was studied, along with variation by sex, age and social depravation status (quintiles of Townsend scores). The number of drugs an individual was taking within a particular year was also examined. RESULTS: In 1995, 40.6% of patients with bipolar disorder were prescribed a psychotropic medication at least twice. By 2009 this had increased to 78.5% of patients. Valproate registered with the greatest increase in use (22.7%) followed by olanzapine (15.7%) and quetiapine (9.9%). There were differences by age and sex; with young (18-30 year old) women having the biggest increase in proportion of time on medication. There were no differences by social deprivation status. By 2009, 34.2% of women of childbearing age were treated with valproate. CONCLUSIONS: Lithium use overall remained relatively constant, whilst second generation antipsychotic and valproate use increased dramatically. Changes in prescribing practice preceded published trial evidence, especially with the use of second generation antipsychotics, perhaps with inferences being made from treatment of schizophrenia and use of first generation antipsychotics. Women of childbearing age were prescribed valproate frequently, against best advice.

OBJECTIVES: Previous studies into the survival differences between individuals with idiopathic pulmonary fibrosis and those with connective tissue disease associated pulmonary fibrosis (CTD-PF) have yielded mixed results. The aim of this study is to compare the survival of individuals with CTD-PF to those with idiopathic pulmonary fibrosis clinical syndrome (IPF-CS) using data derived from The Health Improvement network, a large primary care database in the UK. METHODS: Incident cases of CTD-PF and IPF-CS between the years 2000-2009 were identified. Survival analysis was performed using Kaplan-Meier methods, stratified by type of connective tissue disease. Cox regression was then used to compare mortality rates between the groups, adjusting for age, gender and year of diagnosis. RESULTS: A total of 324 cases of CTD-PF and 2209 cases of IPF-CS were followed up over a mean period of 2.3 years. During this period, 113 (34.9%) cases of CTD-PF and 1073 (48.6%) cases of IPF-CS died. The mortality rates for cases with CTD-PF and IPF-CS were 123.6 per 1000 person years (95%CI: 102.8-148.9) and 229.8 per 1000 person years (95% CI: 216.4-244.0) respectively. After adjusting for age, sex and year of diagnosis, cases with CTD-PF had a better prognosis compared to those with IPF-CS (HR 0.76,95%CI: 0.62-0.92). CONCLUSION: The prognosis of individuals with CTD-PF appears to be significantly better than those with IPF-CS, but remains an important cause of death in patients with connective tissue disease, and requires more effective treatment options.

BACKGROUND: Antidepressant medications have long been implicated as a cause of falls in older people, but there are few data on the risk of falls associated with exposure to serotonin-norepinephrine (noradrenaline) reuptake inhibitors (SNRIs). OBJECTIVE: The aim of this study was to determine the role of SNRIs in older people with a recorded fall in primary care using a case-control approach and a self-controlled case-series analysis of data from The Health Improvement Network (THIN) UK primary care database. METHODS: Cases were 9862 individuals aged >60 years with a first fall recorded between 2003 and 2006. Up to six controls per case were matched by age, sex and primary care practice. For the case-series analysis, we extended our case set to those with a first fall recorded between 2001 and 2008. We estimated odds ratios (ORs) for 'ever', 'current', 'recent', 'previous' or 'never' prescribed SNRIs (and for the other main classes of antidepressants, for comparison) in cases compared with matched controls, using conditional logistic regression. We also examined the effect of the time interval from first prescription to first fall. In the case-series analysis, we compared the rate of occurrence of first falls during episodes of exposure to SNRIs with unexposed periods in our case group. RESULTS: There was an increased risk of current prescribing of SNRIs (adjusted OR 1.79; 95% CI 1.42, 2.25) in first fall cases compared with controls. This was similar in magnitude to that seen with tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). The increase in risk was apparent within the first 28 days after first prescription. The effects were also apparent in the self-controlled case-series analysis, although the magnitudes of effect were slightly smaller; the incidence risk ratio for the period 1-28 days after initiation of treatment compared with unexposed periods was 1.49 (95% CI 1.15, 1.93). CONCLUSIONS: Treatment with SNRIs in older people may be associated with an increased risk of falling. The falls risk profile of SNRIs appears to be similar to that of SSRIs and TCAs.