Gout and the risk of advanced chronic kidney disease in the UK health system: a national cohort study.

OBJECTIVE: Evaluate the association between gout and risk of advanced chronic kidney disease (CKD). DESIGN: Retrospective matched cohort study. SETTING: UK Clinical Practice Research Datalink. PARTICIPANTS: The analysis included data for 68 897 patients with gout and 554 964 matched patients without gout. Patients were aged ≥18 years, registered at UK practices, had ≥12 months of clinical data and had data linked with Hospital Episode Statistics. Patients were excluded for history of advanced CKD, juvenile gout, cancer, HIV, tumour lysis syndrome, Lesch-Nyhan syndrome or familial Mediterranean fever. PRIMARY AND SECONDARY OUTCOME MEASURES: Advanced CKD was defined as first occurrence of: (1) dialysis, kidney transplant, diagnosis of end-stage kidney disease (ESKD) or stage 5 CKD (diagnostic codes in Read system or International Classification of Diseases, Tenth Revision); (2) estimated glomerular filtration rate (eGFR) <10 mL/min/1.73 m²; (3) doubling of serum creatinine from baseline and (4) death associated with CKD. RESULTS: Advanced CKD incidence was higher for patients with gout (8.54 per 1000 patient-years; 95% CI 8.26 to 8.83) versus without gout (4.08; 95% CI 4.00 to 4.16). Gout was associated with higher advanced CKD risk in both unadjusted analysis (HR, 2.00; 95% CI 1.92 to 2.07) and after adjustment (HR, 1.29; 95% CI 1.23 to 1.35). Association was strongest for ESKD (HR, 2.13; 95% CI 1.73 to 2.61) and was present for eGFR <10 mL/min/1.73 m² (HR, 1.45; 95% CI 1.30 to 1.61) and serum creatinine doubling (HR, 1.13; 95% CI 1.08 to 1.19) but not CKD-associated death (HR, 1.14; 95% CI 0.99 to 1.31). Association of gout with advanced CKD was replicated in propensity-score matched analysis (HR, 1.23; 95% CI 1.17 to 1.29) and analysis limited to patients with incident gout (HR, 1.28; 95% CI 1.22 to 1.35). CONCLUSIONS: Gout is associated with elevated risk of CKD progression. Future studies should investigate whether controlling gout is protective and reduces CKD risk.

Concordance of hospitalizations between Clinical Practice Research Datalink and linked Hospital Episode Statistics among patients treated with oral antidiabetic therapies.

PURPOSE: The ability of the Clinical Practice Research Datalink (CPRD) to ascertain all-cause hospitalizations remains unknown. We determined the proportion of hospitalizations in CPRD that were also recorded in Hospital Episode Statistics (HES), and vice versa, among patients initiating oral antidiabetic (OAD) therapy. METHODS: We conducted a retrospective cohort study from October 2009 to September 2012 among OAD-treated patients registered with general practitioners who contribute to CPRD and consent to HES linkage. In CPRD, we identified initial hospitalizations for each calendar year by an Inpatient Referral, Consultation Type code, or Read code indicating an inpatient episode and determined if an admission date was recorded in HES within ±30 days. We then identified initial HES admission dates and determined if a hospitalization was documented in CPRD within ±30 days. Sensitivity analyses were conducted utilizing HES discharge, rather than admission, dates. RESULTS: Among 8574 OAD-treated HES-linked patients in CPRD, 6574 initial hospitalizations across the study period were identified in CPRD, and 5188 (78.9% [95% CI, 77.9%-79.9%]) were confirmed by a HES admission date within ±30 days (median difference, ±3 days [IQR, 1-7 days]). Among 8609 initial hospital admissions in HES, 4803 (55.7% [95% CI, 54.7%-56.8%]) hospitalizations were recorded in CPRD within ±30 days (median difference, ±4 days [IQR, 1-9 days]). Similar results were observed using HES discharge dates. CONCLUSION: A substantial minority of patient-level hospitalization data are nonconcordant between HES and CPRD. Pharmacoepidemiologic studies within CPRD that seek to identify hospitalizations should consider linkage with HES to ensure adequate ascertainment of inpatient events.

Glycaemic, weight, and blood pressure changes associated with early versus later treatment intensification with dapagliflozin in United Kingdom primary care patients with type 2 diabetes mellitus.

AIMS: Early treatment intensification for type 2 diabetes mellitus (T2DM) is often required to achieve glycaemic control and avoid longer-term complications. We assessed associations between early versus later dapagliflozin initiation with changes in glucose control, weight, and blood pressure using UK Clinical Practice Research Datalink (CPRD) data. METHODS: People with T2DM aged ≥18 years, initiating dapagliflozin between November 2012 and August 2016 and with prior oral T2DM therapy (N = 3774), were included. The relationship between early (first intensification after metformin or sulfonylurea monotherapy) and later (second or higher-order intensification) dapagliflozin use and baseline changes in glycated haemoglobin A1c (HbA1c; ≥1.0% absolute reduction), weight (≥5.0% relative loss), and systolic blood pressure (SBP; ≥2 mmHg absolute reduction) after 6-12 months were assessed. RESULTS: Overall, 25% of patients (951 of 3774) were early users and 75% (2823 of 3774) were later users. Later users were older, more likely to be men, and had longer disease duration. Early and later users had similar baseline mean HbA1c levels. For early versus later users, respectively, baseline-adjusted mean (95% confidence interval [CI]) reductions were 1.54% (-1.65, -1.44) versus 1.02% (-1.08, -0.97) in HbA1c, 3.31% (-4.37, -2.25) versus 4.06% (-5.05, -3.07) in weight, and 2.50 mm Hg (-3.89, -1.11) versus 2.84 mm Hg (-3.67, -2.01) in SBP. Early versus later use was associated with a greater likelihood of adjusted HbA1c reduction of ≥1% (odds ratio: 1.68, 95% CI: 1.15-2.45). CONCLUSIONS: Glycaemic benefits were greater with early versus later dapagliflozin intensification. These results support broader and earlier dapagliflozin use.

SGLT-2 Inhibitors and Cardiovascular Risk: An Analysis of CVD-REAL.

BACKGROUND: Prior studies found patients treated with sodium-glucose co-transporter-2 inhibitors (SGLT-2i) had lower rates of death and heart failure (HF). Whether the benefits of SGLT-2i vary based upon the presence of cardiovascular disease (CVD) is unknown. OBJECTIVES: This study sought to determine the association between initiation of SGLT-2i therapy and HF or death in patients with and without CVD. METHODS: The CVD-REAL (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors) study was a multinational, observational study in which adults with type 2 diabetes were identified. Patients prescribed an SGLT-2i or other glucose-lowering drugs (GLDs) were matched based on a propensity score for initiation of an SGLT-2i. Hazard ratios (HRs) for the risk of death, HF, and HF or death in patients with and without established CVD were estimated for each country and pooled. RESULTS: After propensity score matching, 153,078 patients were included in each group. At baseline, 13% had established CVD. Compared with therapy using other GLDs, initiation of an SGLT-2i was associated with lower risk of death in patients with and without CVD (HR: 0.56; 95% confidence interval [CI]: 0.44 to 0.70; and HR: 0.56; 95% CI: 0.50 to 0.63, respectively). There were also associations between SGLT-2i and lower risk of HF (HR: 0.72; 95% CI: 0.63 to 0.82; and HR: 0.61; 95% CI: 0.48 to 0.78, respectively) and the composite of HF or death (HR: 0.63; 95% CI: 0.57 to 0.70; and HR: 0.56; 95% CI: 0.50 to 0.62, respectively) observed in patients with and without established CVD. CONCLUSIONS: In this large, multinational, observational study, initiation of SGLT-2i was associated with lower risk of death and HF regardless of pre-existing CVD. Ongoing clinical trials will provide further evidence regarding the benefit of SGLT-2i in patients without established CVD. (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors [CVD-REAL]; NCT02993614).

A retrospective observational analysis of post-pandemic influenza-related outcomes in the United Kingdom, 2010-2014.

This study set out to evaluate influenza- and respiratory-related illnesses recorded during primary care physician consultations in England following the H1N1 pandemic in 2009 and to enable the development of a dynamic disease model. Data were obtained from the Clinical Practice Research Datalink of primary care records over four influenza seasons (2010-2014). The primary outcome of the study was incidence of influenza- and respiratory-related diagnoses, calculated per practice and by season and age group. Upper respiratory tract infection diagnoses were most frequently recorded (mean seasonal practice level incidence; 3,762 consultations per 100,000 [SD = 1,989]), and influenza-related diagnoses were least frequently recorded across all seasons, except one. Incidence rates for the under 18 population were higher than those for the general population, in particular for upper respiratory tract infection (range of 8,024-9,950 versus 3,228-4,120, respectively) and otitis media diagnoses (2,668-3,652 versus 782-1,057, respectively). For influenza-related diagnoses, the 65+ age group, the 0 to <2 and 2 to <4 groups had a higher risk (risk ratio = 1.33, 1.12 and 1.16, respectively) than other age groups. This study provides valuable insight into the incidence of influenza- and respiratory-related diagnoses in the primary care setting in England, and suggests a higher burden of disease in young children and the elderly. The study also indicates that some influenza illness is likely to be reported under respiratory-related diagnoses, given the low incidence of influenza-related diagnoses in the study.

Impact of increased influenza vaccination in 2-3-year-old children on disease burden within the general population: A Bayesian model-based approach.

INTRODUCTION: During the 2013-2014 influenza season, Public Health England extended routine influenza vaccination to all 2- and 3-year-old children in England. To estimate the impact of this change in policy on influenza-related morbidity and mortality, we developed a disease transmission and surveillance model informed by real-world data. METHODS: We combined real-world and literature data sources to construct a model of influenza transmission and surveillance in England. Data were obtained for four influenza seasons, starting with the 2010-2011 season. Bayesian inference was used to estimate model parameters on a season-by-season basis to assess the impact of targeting 2- and 3-year-old children for influenza vaccination. This provided the basis for the construction of counterfactual scenarios comparing vaccination rates of ~2% and ~35% in the 2- and 3- year-old population to estimate reductions in general practitioner (GP) influenza-like-illness (ILI) consultations, respiratory hospitalizations and deaths in the overall population. RESULTS: Our model was able to replicate the main patterns of influenza across the four seasons as observed through laboratory surveillance data. Targeting 2- and 3-year-old children for influenza vaccination resulted in reductions in the general population of between 6.2-9.9% in influenza-attributable GP ILI consultations, 6.1-10.7% in influenza-attributable respiratory hospitalizations, and 5.7-9.4% in influenza-attributable deaths. The decrease in influenza-attributable ILI consultations represents a reduction of between 4.5% and 7.3% across all ILI consultations. The reduction in influenza-attributable respiratory hospitalizations represents a reduction of between 1.2% and 2.3% across all respiratory hospitalizations. Reductions in influenza-attributable respiratory deaths represent a reduction of between 0.9% and 2.4% in overall respiratory deaths. CONCLUSION: This study has provided evidence that extending routine influenza vaccination to all healthy children aged 2 and 3 years old leads to benefits in terms of reduced utilization of healthcare resources and fewer respiratory health outcomes and deaths.

Glycated Hemoglobin, Body Weight and Blood Pressure in Type 2 Diabetes Patients Initiating Dapagliflozin Treatment in Primary Care: A Retrospective Study.

INTRODUCTION: The present study aimed to describe characteristics of patients with type 2 diabetes (T2D) in UK primary care initiated on dapagliflozin, post-dapagliflozin changes in glycated hemoglobin (HbA1c), body weight and blood pressure, and reasons for adding dapagliflozin to insulin. METHODS: Retrospective study of patients with T2D in the Clinical Practice Research Datalink with first prescription for dapagliflozin. Patients were included in the study if they: (1) had a first prescription for dapagliflozin between November 2012 and September 2014; (2) had a Read code for T2D; (3) were registered with a practice for at least 6 months before starting dapagliflozin; and (4) remained registered for at least 3 months after initiation. A questionnaire ascertained reason(s) for adding dapagliflozin to insulin. RESULTS: Dapagliflozin was most often used as triple therapy (27.7%), dual therapy with metformin (25.1%) or added to insulin (19.2%). Median therapy duration was 329 days [95% confidence interval (CI) 302-361]. Poor glycemic control was the reason for dapagliflozin initiation for 93.1% of insulin-treated patients. Avoiding increases in weight/body mass index and insulin resistance were the commonest reasons for selecting dapagliflozin versus intensifying insulin. HbA1c declined by mean of 9.7 mmol/mol (95% CI 8.5-10.9) (0.89%) 14-90 days after starting dapagliflozin, 10.2 mmol/mol (95% CI 8.9-11.5) (0.93%) after 91-180 days and 12.6 mmol/mol (95% CI 11.0-14.3) (1.16%) beyond 180 days. Weight declined by mean of 2.6 kg (95% CI 2.3-2.9) after 14-90 days, 4.3 kg (95% CI 3.8-4.7) after 91-180 days and 4.6 kg (95% CI 4.0-5.2) beyond 180 days. In patients with measurements between 14 and 90 days after starting dapagliflozin, systolic and diastolic blood pressure decreased by means of 4.5 (95% CI -5.8 to -3.2) and 2.0 (95% CI -2.9 to -1.2) mmHg, respectively from baseline. Similar reductions in systolic and diastolic blood pressure were observed after 91-180 days and when follow-up extended beyond 180 days. Results were consistent across subgroups. CONCLUSION: HbA1c, body weight and blood pressure were reduced after initiation of dapagliflozin in patients with T2D in UK primary care and the changes were consistent with randomized clinical trials. FUNDING: AstraZeneca.

Uptake of childhood influenza vaccine from 2012-2013 to 2014-2015 in the UK and the implications for high-risk children: a retrospective observational cohort study.

OBJECTIVES: To evaluate changes in influenza vaccination rates in healthy and at-risk children following the implementation of the UK's childhood influenza immunisation programme. DESIGN: Observational cohort study before and after initiation of the UK's childhood influenza immunisation programme over three influenza seasons (2012-2013, 2013-2014 and 2014-2015) using data from the Clinical Practice Research Datalink (CPRD). SETTING: More than 500 primary care practices in the UK. POPULATION: All individuals aged 2-17 years on 1 September, with at least 12 months of medical history documented in CPRD were retained in the analysis. INTERVENTION: Starting in 2013-2014, all children aged 2 and 3 years were offered influenza vaccination through general practice, and primary school-aged children were offered influenza vaccination in selected counties in England (described as pilot regions). The vaccination programme was extended to all children aged 4 years in England in 2014-2015. MAIN OUTCOME MEASURE: Cumulative vaccination rate from 1 September to 28 February of the next calendar year as assessed by a time-to-event statistical model (vaccination uptake). Age group, sex, region and type of high-risk medical condition were assessed as predictors. RESULTS: Vaccination uptake increased considerably from 2012-2013 to 2013-2014 in targeted children aged 2-3 years, both in children with a high-risk medical condition (from 40.7% to 61.1%) and those without (from 1.0% to 43.0%). Vaccination rates increased also, though less markedly, in older children. In 2014-2015, vaccination rates remained higher than 40% in healthy children aged 2-3 years, although they decreased slightly from 2013-2014 (from 43.0% to 41.8%). Vaccination rates in older healthy children continued to increase, driven primarily by an increase in children aged 4 years to 31.3% in 2014-2015. CONCLUSIONS: The introduction of a universal childhood vaccination policy in the UK increased vaccination rates for targeted children, including those with high-risk conditions.

Use of demographic and pharmacy data to identify patients included within both the Clinical Practice Research Datalink (CPRD) and The Health Improvement Network (THIN).

PURPOSE: Pharmacoepidemiology researchers often utilize data from two UK electronic medical record databases, the Clinical Practice Research Datalink (CPRD) and The Health Improvement Network (THIN), and may choose to combine the two in an effort to increase sample size. To minimize duplication of data, previous studies examined the practice-level overlap between these databases. However, the proportion of overlapping patients remains unknown. We developed a method using demographic and pharmacy variables to identify patients included in both CPRD and THIN, and applied this method to measure the proportion of overlapping patients who initiated the oral anti-diabetic drug saxagliptin. METHODS: We conducted a cross-sectional study among patients initiating saxagliptin in CPRD and THIN between October 2009 and September 2012. Within both databases, we identified patients: (i) ≥18 years, (ii) newly prescribed saxagliptin, and (iii) with ≥180 days enrollment prior to saxagliptin initiation. Demographic data (birth year, sex, patient registration date, family number, and marital status) and prescriptions (including dates) for the first two oral anti-diabetic drugs prescribed within the study period were used to identify matching patients. RESULTS: Among 4202 CPRD and 3641 THIN patients initiating saxagliptin, 2574 overlapping patients (61% of CPRD saxagliptin initiators; 71% of THIN saxagliptin initiators) were identified. Among these patients, 2474 patients (96%) perfectly matched on all demographic and prescription data. CONCLUSIONS: Within each database, over 60% of patients initiating saxagliptin were included within both CPRD and THIN. Combined demographic and prescription data can be used to identify patients included in both CPRD and THIN.

Drug treatment patterns for the management of men with lower urinary tract symptoms associated with benign prostatic hyperplasia who have both storage and voiding symptoms: a study using the health improvement network UK primary care data.

BACKGROUND: Real-world data on the pharmacological management of men who have lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) are limited. OBJECTIVE: To characterize men with LUTS/BPH who had both storage and voiding symptoms and to evaluate treatment patterns in UK primary care. DESIGN, SETTING AND PARTICIPANTS: This was an observational study of men aged ≥45 years with a diagnosis, symptoms or therapies indicative of LUTS/BPH with both storage and voiding components. These men were identified from the large Health Improvement Network (THIN) database between 1 January 2004 and 30 September 2011. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Drug prescriptions and switching/discontinuation patterns for α1-blockers and antimuscarinics. RESULTS AND LIMITATIONS: We identified 8694 men with a median age of 66.0 (interquartile range [IQR], 59.0-74.0) years. Most (7850; 90.3%) received an α1-blocker, and 2167 (24.9%) received antimuscarinic therapy over a median of 2.1 years. The most commonly prescribed α1-blocker was tamsulosin (81.8%); most frequent antimuscarinics were tolterodine (41.0%), oxybutynin (37.2%) and solifenacin (35.7%). Concomitant prescription of α1-blocker and antimuscarinic therapy (within 30 days of each other) was received by 1160 men (14.8% of α1-blocker-treated men). Of α1-blocker recipients, 3024 (38.5%) discontinued during follow-up, while 1149 (53.0%) discontinued antimuscarinic therapy. Of 2167 men who received an antimuscarinic, 476 (22.0%) switched to another antimuscarinic. Of the three most commonly prescribed antimuscarinics, solifenacin had the lowest proportions of discontinuations (43.0%) and switches (15.3%), and the longest median duration of therapy (90 days, IQR 30-300). General practice consultations accounted for most resource use (5307.9 per 1000 patient-years). CONCLUSIONS: This study presents real-world management of men with LUTS/BPH who have both storage and voiding symptoms. The low proportion of men who received concomitant α1-blocker and antimuscarinic therapy suggests that some patients are sub-optimally treated in routine clinical practice.

Topical prostaglandin fixed combinations in UK primary care: observational study using data from the health improvement network.

PURPOSE: To describe the use of 3 prostaglandin/timolol fixed combinations (FCs) in UK primary care, to summarize characteristics of recipients, and to assess 12-month persistence. METHODS: This retrospective cohort study included first-time recipients of latanoprost/timolol FC, bimatoprost/timolol FC, or travoprost/timolol FC treated between April 1, 2007, and November 30, 2008, identified in The Health Improvement Network database, a large database of anonymized longitudinal electronic medical records of patients treated in UK primary care. Eligible patients were = 18 years old at the index date (date of first prescription). Persistence, defined as a gap =60 days between consecutive prescriptions, was assessed through 12 months post-index for each cohort (Cox proportional hazards models). RESULTS: A total of 2,015 patients were included: latanoprost/timolol FC, n = 898 (44.6%); bimatoprost/timolol FC, n = 733 (36.4%); travoprost/timolol FC, n = 384 (19.1%). The mean age was approximately 72 years across cohorts (p = 0.792). Glaucoma was the diagnosis for >90% of patients in each cohort. Twelve-month persistence was similar across treatments: latanoprost/timolol FC: 38.2%; bimatoprost/timolol FC: 38.6%; travoprost/timolol FC: 38.3% (p = 0.985). Mean time to therapy change for nonpersistent patients was also similar: 143.3 ± 89.8, 151.0 ± 87.9, and 151.8 ± 87.7 days, respectively (p = 0.095). Among persistent patients, additional therapy was prescribed for 36.2%, 41.7%, and 41.5% of patients, respectively. Among nonpersistent patients, 64.0%, 70.4%, and 69.2%, respectively, restarted the index therapy. CONCLUSIONS: The largest proportion of first-time recipients of prostaglandin/beta-blocker FC products treated in UK primary care was prescribed latanoprost/timolol FC. Twelve-month persistence was similar (<40%) across the 3 FCs evaluated.

Generalisability of The Health Improvement Network (THIN) database: demographics, chronic disease prevalence and mortality rates.

INTRODUCTION: The degree of generalisability of patient databases to the general population is important for interpreting database research. This report describes the representativeness of The Health Improvement Network (THIN), a UK primary care database, of the UK population. METHODS: Demographics, deprivation (Townsend), Quality and Outcomes Framework (QOF) condition prevalence and deaths from THIN were compared with national statistical and QOF 2006/2007 data. RESULTS: Demographics were similar although THIN contained fewer people aged under 25 years. Condition prevalence was comparable, e.g. 3.5% diabetes prevalence in THIN, 3.7% nationally. More THIN patients lived in the most affluent areas (23.5% in THIN, 20% nationally). Between 1990 and 2009, standardised mortality ratio ranged from 0.81 (95% CI: 0.39-1.49; 1990) to 0.93 (95% CI: 0.48-1.64; 1995). Adjusting for demographics/deprivation, the 2006 THIN death rate was 9.08/1000 population close to the national death rate of 9.4/1000 population. CONCLUSION: THIN is generalisable to the UK for demographics, major condition prevalence and death rates adjusted for demographics and deprivation.

Evaluation of varenicline as an aid to smoking cessation in UK general practice - a THIN database study.

OBJECTIVES: Varenicline is a licensed smoking cessation medication in the EU, USA and many other countries worldwide. This study was designed to assess its effectiveness in a UK general practice setting. METHODS: The main outcome measure was the rate of smoking cessation, defined as the seven-day point prevalence after six months from starting varenicline. Varenicline users were identified from records in The Health Improvement Network (THIN) database. A questionnaire on smoking cessation was sent to patients who commenced treatment close to the selection date (six months prior to the date of questionnaire dispatch). RESULTS: The response rate was 26.4%: 193 responses were received. Ninety percent had previously attempted to stop smoking and 87.4% had used nicotine replacement therapy during the previous attempt to stop smoking. The overall smoking cessation rate was 49.5%. There was a strong association between the duration of varenicline treatment and smoking cessation. Patients who reported using varenicline for 9-12 weeks were 11 times more likely to stop smoking than those who completed less than two weeks of treatment. There was some evidence that patients with a longer history of smoking were less likely to stop. No association was observed between smoking cessation and: previous number of cigarettes smoked per day; number of previous attempts to stop smoking; or motivations for stopping. CONCLUSIONS: Varenicline appeared to be a useful pharmacological aid to smoking cessation in a general practice setting. The observed effectiveness was similar to the efficacy estimates from previously reported clinical trials. However, the response rate was lower than expected and responders tended to be older, more likely to suffer from chronic obstructive pulmonary disease and to live in more affluent areas than non-responders. Responses were self-reported and not clinically validated therefore recall bias may be an issue.

The importance of defining periods of complete mortality reporting for research using automated data from primary care.

PURPOSE: To define periods of acceptable mortality reporting in primary care and to demonstrate through examples the implication for research using automated medical data. METHODS: Annual death counts were obtained for each primary care practice participating in The Health Improvement Network "THIN" (UK). Expected counts were calculated from national death rates, accounting for the practice's age/sex structure. The standardized mortality ratio (SMR) was calculated with 95% confidence intervals (CI). A visual review process was undertaken to assign the year from which the practice had acceptable mortality reporting (AMR). The process involved reviewer pairs who were blinded to each other's decisions. Patterns of death reporting were checked. The AMR year was applied as a filter to THIN data to assess its impact on the SMR. RESULTS: For most practices the SMR was relatively stable and the AMR year was easily identified with 86% agreement between the blinded reviewer pairs. Applying the AMR to THIN removed under-reporting of death. However, the total computerized follow-up reduced from 37 to 32 million patient-years. Problematic death recording patterns included some practices keeping only live patient records when converting their software systems thereby creating 'immortal periods' prior to this moment, and peaks occurring when practices updated the vital status of their patients' records. CONCLUSIONS: This is the first time that an external standard has been used to assess completeness of mortality in automated primary care data. The resulting AMR year provides a natural filter for research and avoids biases associated with 'immortal periods', record updating and under-reporting.

Prescribing trends and drug budget impact of the ARBs in the UK.

OBJECTIVES: Angiotensin II receptor blockers (ARBs) were introduced into the UK antihypertensive drug market at a premium price relative to other antihypertensives during a period of evolving evidence about hypertension treatment. This study aimed to determine the UK antihypertensive drug budget impact as the first ARB market launched in December 1994 and what proportion of the increase was directly attributable to ARBs. METHODS: Prescriptions for oral antihypertensives were identified from The Health Improvement Network database. Drug prices were based on the Chemist & Druggist January 2005 pricelist estimating real expenditure growth. Expenditure increases were disaggregated into the number of patients receiving antihypertensive drug prescriptions, the number of antihypertensive prescriptions per patient treated, and the average drug expenditure per antihypertensive prescription. RESULTS: The annual ARB prescription frequency increased from 0.04% in 1995 to 6.57% in 2004. Expenditure for antihypertensive drugs was estimated at pound465,862,416 in 1995 and pound1,458,268,104 in 2004 (2005 values), reflecting a 213% real rate of increase. Use of ARBs accounted for only 9.3% (range: 5.8%-12.5%) of the average drug expenditure. Treatment prevalence rose from 11.30% in 1995 to 16.90% in 2004, while the average number of antihypertensive drug prescriptions per patient increased from 9.34 to 13.46 per year. The average expenditure per antihypertensive drug prescription increased over time reflecting a product shift toward more expensive therapies. CONCLUSIONS: ARBs accounted for only 9.3% of the 213% increase in antihypertensive drug expenditure after their introduction. A substantial portion of the impact reflected increases in treatment prevalence and in the number of prescriptions per patient.

Comparing cost-effectiveness analyses of anti-hypertensive drug therapy for decision making: mission impossible?

The purpose of this literature review was to compare the methodology used in the most recently published cost-effectiveness studies of antihypertensive treatments, and to identify methodological strengths and weaknesses that indicate the study's potential as a useful, decision-making tool. Based on the results of a search of several databases, spanning the years 1995 to 2000, 10 cost-effectiveness studies were identified. Although the majority of the studies reported their cost-effectiveness ratio in "costs per year of life gained," the studies also considered a varying range of components including additional end points. The methodology used to measure effectiveness, the cost variables included, and the characteristics of the patient population varied significantly across studies. Due to this lack of conformity, it would be difficult, if not impossible, to compare the results and draw conclusions about the relative cost-effectiveness of different types of antihypertensive drug therapies. This lack of uniform comparison across studies is likely to draw criticism from both the clinical and health-care decision-making communities. Future studies within this field should be thorough and useful for decision making. It is suggested that short-term outcomes should include systolic and diastolic blood pressure measurements and long-term outcomes should include end points such as myocardial infarction, stroke, congestive heart failure and renal events. Other positive outcomes such as a more favorable side-effect profile, should be used to enhance the primary outcomes. Additionally, when subpopulations are considered in submodels, studies should address the issue of generalizability. Cost calculations should be transparent and related to the perspective of the study. Modeling the cost-effectiveness of a drug may be an acceptable method provided that data sources and assumptions are valid and transparent.