Scientific
publications

INTRODUCTION: Sexual dysfunction (SD) and lower urinary tract symptoms (LUTS) are highly prevalent in men and increase with age. Previous studies have shown that LUTS and SD are highly associated in men, but most have not distinguished between voiding and storage LUTS. Aims. Assess impact of voiding and storage LUTS on recorded diagnosis of SD in men in U.K. general practice. METHODS: Identified records of patients with SD and storage (e.g., overactive bladder) and voiding LUTS (e.g., benign prostatic hyperplasia) from a population-based study using The Health Improvement Network database with records from 333 general practices. Study period was 2000-2007; study population was men aged >or= 18 years. MAIN OUTCOME MEASURES: Prevalence rates of SD, and storage and voiding LUTS on January 1 of each year from 2000 to 2007. RESULTS: Overall prevalence of recorded SD rose from 1.7% in 2000 to 4.9% in 2007. The prevalence of storage and voiding LUTS also increased. Median age at diagnosis was 60 years for erectile dysfunction (ED), 62 years for other SD, 62 years for storage LUTS, and 61 years for voiding LUTS. Compared to men with no LUTS, odds ratios (95% CI) for ED were as follows: storage LUTS, 3.0 (2.6-3.4); voiding LUTS, 2.6 (2.4-2.7); and both voiding and storage LUTS, 4.0 (3.4-4.8). Among the 11,327 men with any recorded LUTS and ED at the beginning of 2007, LUTS diagnosis preceded SD in 63.1% of patients by a mean of 4.8 years. CONCLUSIONS: Prevalence of SD was significantly higher in the presence of either storage or voiding LUTS compared to men with no recorded LUTS. The diagnosis of LUTS preceded SD in the majority of cases. Further research into the interrelationships between functional problems of the genitourinary tract may have implications for current treatment approaches and future therapeutic developments.

Case-crossover and case-series analyses are 2 epidemiologic approaches that can be used to evaluate the association of exposures with acute events. Using a primary care database from the United Kingdom and these 2 statistical approaches, the authors investigated the impact of using benzodiazepines, nonbenzodiazepine hypnotics, beta-blockers, selective serotonin reuptake inhibitors, tricyclic antidepressants, opioids, and antihistamines on the risk of motor vehicle crashes in 1986-2004. For 49,821 individuals aged 18-74 years, involvement in a motor vehicle crash was documented. The outcome of the case-crossover analyses varied according to the choice of control period, so the case-series approach was preferred. The first 4 weeks of treatment with a combined acetaminophen and opioid preparation was associated with an increased risk of motor vehicle crash (incidence rate ratio = 2.06, 99% confidence interval: 1.84, 2.32), as was use of an opioid alone (incidence rate ratio = 1.70, 99% confidence interval: 1.39, 2.08) and benzodiazepines (incidence rate ratio = 1.94, 99% confidence interval: 1.62, 2.32). Use of selective serotonin reuptake inhibitors, nonbenzodiazepine hypnotics, and antihistamines for more than 4 weeks was associated with motor vehicle crash, but shorter term use was not. The results obtained are broadly consistent with those from well-designed case-control studies and demonstrate how case-only techniques optimize the use of routinely collected data for epidemiologic studies.

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.

PURPOSE: Data from a cohort study were used to investigate death and cause of death (COD) recording on the THIN UK primary care database. METHODS: Subjects from 118 practices had a body mass index recorded, 2002-2003 (index date), no recent pregnancy or emotional event, or cancer. Coded and free text entries were searched for a COD for deaths dated < or = 485 days after index date. External documents were requested when date or COD were unclear, suicide was possible, and for a random sample of 40 patients with a COD identified. RESULTS: Five of 1399 deaths dated within 1 year of the index date had not died (positive predictive value 99.6%) and 4 of 222 dated within 366-485 days had died during the year (sensitivity 99.7%). A database COD was identified for 887 (63.4%) with external documents received for 597 (92.8% requested). Of 40 compared with external sources, the underlying COD was on the database in 33 (82.5%), and could be identified as such in 26 (65%). The date was within 1 day of that on external documents in 504 (94.9%) with a date of death but 3 (5.7%) with only a transfer-out of practice date. One of seven suicides was recorded as such. CONCLUSION: Any database record of death or its date is reliable, but transfer-out date is often later. Studies of COD or acute, potentially fatal conditions will miss cases unless a COD is obtained for all fatalities. Most suicides are not noted as such on the electronic record.

BACKGROUND: Insulin glargine (glargine) and premixed insulins (premix) are alternative insulin treatments. This analysis evaluated glycaemic control in 528 patients with type 1 (n = 183) or type 2 (n = 345) diabetes, after switching from premix to a glargine-based regimen, using unselected general practice (GP) data. METHODS: Data for this retrospective observational analysis were extracted from a UK GP database (The Health Improvement Network). Patients were required to have at least 12 months of available data, before and after, switching from premix to a glargine-based regimen. The principal analysis was the change in HbA1c after 12 months of treatment with glargine; secondary analyses included change in weight, bolus usage and total daily insulin dose. Inconsistent reporting of hypoglycemic episodes precludes reliable assessment of this outcome. Multivariate analyses were used to adjust for baseline characteristics and confounding variables. RESULTS: Both cohorts showed significant reduction in mean HbA1c 12 months after the switch: by -0.67% (p < 0.001) in the type 1 cohort and by -0.53% (p < 0.001) in the type 2 cohort (adjusted data). The size of HbA1c improvement was positively correlated with baseline HbA1c; patients with a baseline HbA1c > or = 10% had the greatest mean reduction in HbA1c, by -1.7% (p < 0.001) and -1.2% (p < 0.001), respectively. The proportion of patients receiving co-bolus prescriptions increased in the type 1 (mean 24.6% to 95.1%, p < 0.001) and type 2 (mean 16.2% to 73.9%, p < 0.001) cohorts. There was no significant change in weight in either cohort. Total mean insulin use increased in type 2 diabetes patients (from 0.67 +/- 1.35 U/Kg to 0.88 +/- 1.33 U/Kg, p < 0.001) with a slight decrease in type 1 diabetes patients (from 1.04 +/- 2.51 U/Kg to 0.98 +/- 2.58 U/Kg, p < 0.001). CONCLUSION: In everyday practice, patients with type 1 or type 2 diabetes inadequately controlled by premix insulins experienced significant improvement in glycaemic control over 12 months after switching to a glargine-based insulin regimen. These findings support the use of a basal-bolus glargine-based regimen in patients poorly controlled on premix.

OBJECTIVES: There are concerns that exogenous testosterone therapy may be associated with adverse cardiovascular effects, increases in risk of breast or uterus cancer and alterations in insulin sensitivity. Objective of this study was to explore the safety of testosterone therapy in actual clinical practice. METHODS: Data from the General Practice Research Database and the Health Improvement Network was used, including computerised medical records of UK general practitioners. The study population included women aged 18+ years prescribed testosterone, administered through implants (72.2%), tablets (18.4%) or injections (7.9%). Each testosterone user was matched by age and practice to three control patients. Cox proportional hazards models were used to compare the rates of several outcomes. RESULTS: The study population included 8412 women, 2103 testosterone users and 6309 controls. There were no statistically significant differences between the cohorts in the rates of cerebrovascular disease, ischemic heart disease, breast cancer, deep venous thrombosis/pulmonary embolism, diabetes mellitus or acute hepatitis. The rate of breast cancer was comparable between testosterone users and control patients. The rate of androgenic events was increased in the testosterone cohort (relative rate of 1.55 [95% CI 1.21-1.97]). Differences in outcomes between the cohorts were generally comparable across subgroups based on age and use of hormone therapy. CONCLUSIONS: This study found no major increase in the risk of cardiovascular diseases or breast cancer in women using testosterone (implants, tablets, or injections), while the risk of androgenic events was increased. It would be useful to conduct similar studies at lower doses with transdermal testosterone.

PURPOSE: To examine the use of pregabalin in patients with painful neuropathic disorders under the care of general practitioners (GPs) in the U.K. MATERIALS AND METHODS: Using a large U.K. database of GP encounters, we identified all persons aged > or = 18 years with at least one GP encounter with a diagnosis of a painful neuropathic disorder (eg, postherpetic neuralgia, diabetic peripheral neuropathy) between January 1, 2004 and July 31, 2006. Among these patients, we then identified those who initiated therapy with pregabalin; the date of initial receipt of pregabalin was designated the "index date." We then examined use of pregabalin over the 6-month period following this date ("follow-up"), as well as changes in the use of other pain-related medications (eg, opioids, tricyclic antidepressants [TCAs], other antiepileptics [AEDs]) between the 6-month period preceding the index date ("pretreatment") and follow-up. Patients with less than 6 months of pretreatment and follow-up data were excluded, as were those without any encounters during pretreatment for a painful neuropathic disorder. RESULTS: A total of 1,400 patients (1.4% of all identified patients with painful neuropathic disorders) initiated therapy with pregabalin and met all other entry criteria; mean age was 62 years, and 58% were women. During pretreatment, most (54%) patients received three or more different types of pain-related medications. During follow-up, patients averaged four prescriptions for pregabalin, totaling 93 therapy days. Compared with pretreatment, fewer patients received other pain-related medications during follow-up, including TCAs (37% during pretreatment vs. 27% during follow-up), opioids (64% vs. 55%), and AEDs other than pregabalin (36% vs. 16%) (all P < 0.01). CONCLUSIONS: In the U.K., many patients prescribed pregabalin by their GPs may have been refractory to other pain-related medications. Use of these medications declined following initiation of pregabalin therapy.

The objectives of the study were to determine whether identifying patients with metabolic syndrome (MetS) (as defined by International Diabetes Federation [IDF] criteria) among patients with diabetes would affect the decision to prescribe statin for primary prevention of cardiovascular disease (CVD), based on currently available public health guidelines. We analysed the most recent recorded CVD risk profiles obtained from electronic patient files from 304 general practices in England and Wales. Of 60,258 patients with diabetes, 11,005 men and women aged 30-74 years fulfilled criteria for primary CVD prevention and were not on lipid-lowering drugs. Outcome data were extrapolated to an estimated national diabetes prevalence of 3.6%. Identifying MetS in this group of patients would produce an additional 29,536 (8.4%; 95% CI: 7.7, 9.0), 104,288 (29.6%; 95% CI: 28.5, 30.7) and 147, 328 (41.9%; 95% CI: 40.8, 43.0) patients nationally who would not have been eligible otherwise for primary CVD prevention strategies with statins, based on the Joint British Societies', the National Institute for Health and Clinical Excellence and the General Medical Services contract guidelines, respectively. The sensitivity and positive predictive value of these different strategies to detect metabolic syndrome were 87.5% and 69.1%; 57.3% and 76.8%; and 37.8% and 70.2%, respectively. In conclusion, among individuals with diabetes, identifying patients with MetS may further increase the use of statin therapy for primary CVD prevention.

BACKGROUND: Insulin glargine (glargine) and insulin NPH (NPH) are two basal insulin treatments. This study investigated the effect on glycaemic control of switching from a NPH-based regimen to a glargine-based regimen in 701 patients with type 1 (n= 304) or type 2 (n= 397) diabetes, using unselected primary care data. METHODS: Data for this retrospective observational study were extracted from a UK primary care database (The Health Improvement Network). Patients were required to have at least 12 months of data before and after switching from NPH to glargine. The principal analysis was the change in HbA(1c) after 12 months treatment with glargine; secondary analyses included change in weight and total daily insulin dose. Inconsistent reporting of hypoglycemic episodes precludes reliable reporting of this outcome. Multivariate analyses were used to adjust for baseline characteristics and confounding variables. RESULTS: After adjustment, both diabetic cohorts showed statistically significant reductions in mean HbA(1c) 12 months after the switch, by 0.38% (p < 0.001) in type 1 patients and 0.31% (p < 0.001) in type 2 patients. Improvement in HbA1c was positively correlated with baseline HbA(1c); patients with baseline HbA(1c) > or = 8% had reductions of 0.57% (p < 0.001) and 0.47% (p < 0.001), respectively. There was no significant change in weight or total daily insulin dose while on glargine. The majority of patients received a basal-bolus regimen prior to and after the switch (mean 79.3% before and 77.2% after switch in type 1 patients, and 80.4% and 76.8%, respectively in type 2 patients, p > 0.05). CONCLUSION: In routine clinical practice, switching from NPH to glargine provides the opportunity for improving glycaemic control in diabetes patients inadequately controlled by NPH.

AIMS: To assess the effect of statins on a range of health outcomes. METHODS: We undertook a population-based cohort study to assess the effect of statins on a range of health outcomes using a propensity score-based method to control for differences between people prescribed and not prescribed statins. We validated our design by comparing our results for vascular outcomes with the effects established in large randomized trials. The study was based on the United Kingdom Health Improvement Network database that includes the computerized medical records of over four and a half million patients. RESULTS: People who initiated treatment with a statin (n = 129,288) were compared with a matched sample of 600,241 people who did not initiate treatment, with a median follow-up period of 4.4 years. Statin use was not associated with an effect on a wide range of outcomes, including infections, fractures, venous thromboembolism, gastrointestinal haemorrhage, or on specific eye, neurological or autoimmune diseases. A protective effect against dementia was observed (hazard ratio 0.80, 99% confidence interval 0.68, 0.95). There was no effect on the risk of cancer even after > or =8 years of follow-up. The effect sizes for statins on vascular end-points and mortality were comparable to those observed in large randomized trials, suggesting bias and confounding had been well controlled for. CONCLUSIONS: We found little evidence to support wide-ranging effects of statins on health outcomes beyond their established beneficial effect on vascular disease.

RATIONALE: Previous studies have suggested that people with idiopathic pulmonary fibrosis (IPF) may be at increased risk of vascular disease. OBJECTIVES: To quantify the risk of cardiovascular disease before and after a diagnosis of IPF. METHODS: We used computerized primary care data from the Health Improvement Network to quantify the relative risk of having a cardiovascular event (acute coronary syndrome, angina, atrial fibrillation, deep-vein thrombosis, and cerebrovascular accident) either before or after having a diagnosis of IPF in comparison to age, sex, and community-matched general population control subjects. MEASUREMENTS AND MAIN RESULTS: Our study included 920 incident case subjects of IPF (mean age at diagnosis, 71 yr; 62% male) and 3,593 matched control subjects. There was an increased risk of acute coronary syndrome (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.15-2.03), angina (OR, 1.84; 95% CI, 1.48-2.29) and deep-vein thrombosis (OR, 1.98; 95% CI, 1.13-3.48) in the period before the diagnosis of IPF. During the follow-up period, there was a marked increased risk of acute coronary syndrome (rate ratio [RR], 3.14; 95%CI, 2.02-4.87) and deep-vein thrombosis (RR, 3.39; 95% CI, 1.57-7.28). None of these estimates were confounded by smoking habit or modified by age or sex. CONCLUSIONS: People with IPF have an increased risk of vascular disease in comparison with the general population. This effect is most marked for acute coronary syndrome and deep-vein thrombosis after the diagnosis of IPF has been made.

OBJECTIVE: To estimate the discontinuation rates of anticholinergic medications used for the treatment of lower urinary tract symptoms in women. METHODS: A large administrative database was used for this study. Women aged 18 years and older who were prescribed anticholinergic medications were included. An overall and drug-specific discontinuation rate for nine different anticholinergic medications was estimated. Covariates examined included number of prior drug classes used, number of switches performed, number of prior drug episodes, year of initiation, age, and history of smoking. The Kaplan-Meier method was used to estimate an overall discontinuation rate. A Cox multivariable regression was performed for the drug-specific analysis. RESULTS: There were 49,419 episodes of anticholinergic therapy available for analysis from 29,369 women. The average number of treatment episodes and number of drug classes prescribed per patient were 1.65+/-1.31 and 1.54+/-0.57, respectively. The median time for overall anticholinergic drug discontinuation was 4.76 months. The 6-month unadjusted cumulative incidence of discontinuation was 58.8% (95% confidence interval [CI] 58.4-59.3). The percentage of episodes in which women switched to another medication was 15.8% (95% CI 15.4-16.1). At 6 months, the adjusted cumulative incidence of discontinuation was as follows: oxybutynin 71% (95% CI 68.4-73.5), tolterodine tartrate 61% (59.4,64.3), extended-release oxybutynin 57% (95% CI 55.1-59.4), and extended-release tolterodine tartrate 54% (95% CI 52.3-57.7). CONCLUSION: Discontinuation rates for anticholinergic medications are high regardless of the class of medication used. LEVEL OF EVIDENCE: II.

OBJECTIVE: To determine an appropriate age threshold at which to prescribe aspirin for primary cardiovascular disease (CVD) prevention among men and women without diabetes. DESIGN: Cross-sectional study. SETTING: 304 general practices in England and Wales contributing to The Health Improvement Network (THIN) electronic patient files. PARTICIPANTS: Subjects aged between 30 and 75 years without diabetes, not prescribed any lipid-lowering treatment and with no previous history of CVD. Subjects had to have been registered by their practices for the whole of the preceding 12 months to be included in the analysis. OUTCOMES MEASURES: Relation between age and coronary heart disease (CHD) risk, and the age threshold at which subjects without diabetes develop an estimated 10-year CHD risk of >or=10%. RESULTS: The age transition from <10% to >10%, 10-year CHD risk for men and women without diabetes occurred at ages 47.8 for men and 57.3 for women. CONCLUSIONS: In the absence of significant bleeding risks, aspirin should routinely be considered for all men and women without diabetes above the ages of 48 and 57 years, respectively, for primary CVD prevention. For subjects below these age thresholds or for those above the age of 75 years, the decision to initiate aspirin should be based on a patient's individual cardiovascular risk profiles. These proposed age thresholds aim to take into account a patient's gender, bleeding risk and the cardioprotective benefits of low-dose aspirin treatment.