A survey of patients' attitudes to clinical research.

Every year hundreds of patients voluntarily participate in clinical trials across Ireland. However, little research has been done as to how patients find the experience. This survey was conducted in an attempt to ascertain clinical trial participants' views on their experience of participating in a clinical trial and to see and how clinical trial participation can be improved. One hundred and sixty-six clinical trial participants who had recently completed a global phase IV cardiovascular endpoint clinical trial were sent a 3-page questionnaire. Ninety-one (91%) respondents found the experience of participating in a clinical trial a good one with 85 (84.16%) respondents saying they would recommend participating in a clinical trial to a friend or relative and eighty-five (87.63%) respondents feeling they received better healthcare because they had participated in a clinical trial.

Prevalence of dyslipidaemia in statin-treated patients in Ireland: Irish results of the DYSlipidaemia International Study (DYSIS).

BACKGROUND: Statins are proven to reduce cardiovascular risk; however, substantial risk remains in patients on statin therapy. Persisting dyslipidaemia is likely to play a contributory role. AIM: To assess the prevalence of persisting lipid abnormalities in patients treated with statins. METHODS: DYSIS was a cross-sectional study of 22,063 patients in Europe and Canada. 900 Irish patients participated. All patients were ≥ 45 years and treated with statins for ≥ 3 months. Data were collected from the patients' records. ESC guidelines were used to classify risk and to define lipid levels. RESULTS: Mean age was 66.1 years with women representing 40.7%. 78.6% were high-risk patients; that is 53.9% with cardiovascular disease (CVD), 20.1% with diabetes and 15.9% with a SCORE risk ≥ 5%. Total cholesterol was not at goal in 34.4% of all patients. LDL-C was elevated in 30.8% of all patients and in 30% at high risk. Low HDL-C was found in 34.7% of high-risk patients compared to 16.9% of patients with an ESC score <5%. In diabetics without CVD, low HDL-C and elevated TGs were found in 46 and 44.3%, respectively. CONCLUSIONS: Despite statin therapy, a significant number of patients have persistent dyslipidaemia. While LDL-C targets are suboptimal in three out of ten patients, the prevalence of low HDL-C and high TGs in high-risk patients is greater than one in three. A more integrated approach to the treatment of patients with dyslipidaemia is warranted. Clinical trials are needed to assess the impact of therapies that raise HDL-C and lower elevated TGs.

Hypertension in Ireland: public awareness and doctors choice of therapy.

BACKGROUND: Hypertension is the commonest medical condition in Ireland. AIMS: (1) To examine the level of awareness of blood pressure (BP) in the population and (2) to ascertain the opinion of general practitioners (GPs) in diagnosis and management of hypertension. METHODS: BP measurements and assessment of BP awareness were performed in a sub-sample of the general population (n = 1,071). The opinion of GPs (n = 1,037) on hypertension was determined in a postal survey. RESULTS: Amongst the population sampled (45 ± 13 years, mean age ± SD), almost half had elevated BP (>140/90 mmHg) but only half of those were already on antihypertensives. 40% had no knowledge of their BP and 54% were not aware of what constituted normal BP. While some 80% of GPs said they followed British guidelines, their practice was more in keeping with the European guidelines. Approximately, 90% of GPs required ambulatory BP recording to confirm diagnosis of hypertension. First choice antihypertensive agents were ACE inhibitors and angiotensin receptor antagonists in younger patients and diuretics and ACE inhibitors in older patients. CONCLUSION: These results suggest that there is a need for further public education on BP and nationally agreed hypertension guidelines.

EUROASPIRE (European Action on Secondary Prevention through Intervention to Reduce Events) III--a comparison of Irish and European results.

The EUROASPIRE III audit was a Europe-wide study which took place in 2006/2007. The objective was to examine the control of risk factors in subjects with established cardiovascular disease. Here, we compare the Irish results to those of the other 21 European countries which participated. Control of blood cholesterol was significantly better in Irish participants, with 73% below the target of 4.5 mmol/l. Blood pressure control was less satisfactory in both Irish and European individuals, with an average of 52% of Irish participants not achieving blood pressure targets. Medication usage was high throughout, particularly anti-platelet agents, beta-blockers and, especially in Ireland, statins. Obesity figures were particularly high in Ireland and throughout Europe, with 82% Irish men and women either overweight or obese. Smoking figures in Irish women were also of concern, with 24% continuing to smoke. Cardiac rehabilitation attendance was particularly high in Ireland, with 68% attending; substantially higher than the European figure of 34%. In common with the rest of Europe, current control of body weight and blood pressure in Ireland is unsatisfactory and in need of increased consideration on the part of both patients and healthcare professionals.

Significant psychological morbidity occurs in irritable bowel syndrome: a case-control study using a pharmacy reimbursement database.

BACKGROUND: Psychological problems are associated with IBS but the strength of this association is unclear. AIM: To assess co-prescribing of antispasmodic and CNS-acting drugs through a nested case-control study. METHODS: A national dispensing database identified patients who were first dispensed antispasmodic medicines for a continuous 3-month period or more during 2006, using 2005 as a run-in period. Each patient was matched with four control patients and excluded if they received drugs indicated for IBD. RESULTS: Four hundred and seven patients commenced antispasmodic drugs during 2006. These patients were matched with 1628 controls. In 2005, patients subsequently prescribed antispasmodics were 2-3 times more likely to receive CNS-acting drugs than controls. In the year following commencement of IBS therapy, patients were 2-4 times more likely than controls to be prescribed CNS-acting drugs including antidepressants (35.4% vs. 9.3%), anxiolytics (27.8% vs. 8.8%), antipsychotics (9.8% vs. 3.3%) and hypno-sedatives (32.7% vs. 11.3%; P < 0.0001). The adjusted OR (95% CI) for antidepressant, anxiolytic, hypnosedative and antipsychotic prescribing in IBS patients were 3.81 (2.79-5.20), 2.84 (2.12-3.81), 2.62 (1.91-3.60) and 2.58 (1.80-3.66), respectively. CONCLUSIONS: Patients prescribed ongoing therapy for presumed IBS are 2-4 times more likely to be prescribed CNS-acting drugs than controls, providing evidence of psychological comorbidity in IBS.

Epidemiology and economics of statin use.

In 2006 the State supported the purchase of statins by some Euro 120 million for some 466,366 patients. While about 50% is for secondary prevention of heart disease a disproportionate number of women are receiving treatment for primary prevention. For proprietary agents the monthly cost was largely explained by price and dosage (mg/day) and the average varied from Euro 29.2 for rosuvastatin (11 mg), Euro 38.2 simvastatin (21 mg), Euro 39.1 atorvastatin (19 mg), Euro 42.7 pravastatin (21 mg) and Euro 31.8 for generic prava/simvastatin (21 mg). Generic substitution for pravastatin and simvastatin would save Euro 6.4m. Applying the drug prices corresponding in the United Kingdom would result in savings of some Euro 35m per annum. While the increasing use of statins is justified on cost benefit/analysis considerable savings could be made through choice of the more potent statins, a greater use of generics and a flatter dose price structure.

An HPLC method for the determination of the free cortisol/cortisone ratio in human urine.

The measurement of the urinary free cortisol-cortisone ratio has been reported to be a sensitive indicator of renal 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD 2) activity. This converts biologically active cortisol to inactive cortisone. A decrease in its activity (e.g. through disease or inhibition caused by a therapeutic agent or a foodstuff) may increase cortisol levels and susceptibility towards hypertension. The method presented here uses a simple isocratic tandem column HPLC system. The method has been validated and found to be robust and reproducible. The lower limit of quantification (LLOQ) was found to be 10 ng/mL for both cortisol and cortisone. Samples of urine (n = 99) from patients, most of whom were on complex combinations of drugs, were analyzed and 92% of samples were found to give successful results with this method (cortisol and cortisone above LLOQ). The ratio ranged from 0.07 to 5.61. No interferences were noted from the drugs that the patients were taking. It was also found that a morning spot urine sample gave comparable results to 24 h collection samples, thus making sample collection much easier.

Matrix metalloproteinase-9 polymorphism contributes to blood pressure and arterial stiffness in essential hypertension.

Arterial stiffness is an independent predictor of cardiovascular events in a hypertensive population. Serum levels of matrix metalloproteinase (MMP)-9 are associated with arterial stiffness and predict cardiovascular risk. We investigated the role of MMP-9 polymorphism -1562C>T on blood pressure (BP) and arterial stiffness in a newly diagnosed hypertensive population. Untreated hypertensive patients (n=215, mean age 46+/-13 years) were studied. Supine BP, carotid-femoral pulse wave velocity (PWV) and augmentation index were assessed. Serum biochemistry and plasma MMP-9 concentrations were measured and genotyping performed following extraction of genomic DNA. BP, aortic PWV and serum MMP-9 levels were significantly higher in T-allele carriers of the -1562C>T polymorphism with a significant gene-dose effect (P<0.0001). In a stepwise regression model adjusting for known or likely determinants, the 1562C>T polymorphism emerged as an independent predictor of systolic BP (R(2)=0.25, P<0.0001), diastolic BP (R(2)=0.16, P<0.0001) and PWV (R(2)=0.47,P<0.0001). This is the first study to show the effect of MMP-9 polymorphism on BP and aortic stiffness in a hypertensive population. These results suggest that hypertensive patients carrying the T allele may be at increased risk of cardiovascular events.

An evaluation of the effects of renal artery stenting in renovascular hypertension.

Renal artery stenosis is a common cause (1-6%) of secondary hypertension. Renal artery stenting has recently been employed as an adjunct to antihypertensive medication. We evaluated 92 patients who underwent renal angiography of whom 30 were stented. There was a reduction (p < 0.01) in blood pressure immediately post renal artery stenting--systolic BP from 157 +/- 20 to 140 +/- 21 mmHg and diastolic BP from 81 +/- 13 to 72 +/- 12 mmHg was sustained at 6 months follow up (148 +/- 20/76 +/- 12 mmHg) in the outpatients' clinic. The amount of antihypertensive medication did not differ post stenting--2.7 +/- 1.2 pre vs 2.7 +/- 1.2 drugs post procedure. Renal artery stenting did not provide a 'cure' for any patient with atherosclerotic renovascular hypertension and until the results of randomized studies are known we believe use should be restricted.

Acute haemodynamic effects of cigarette smoking in healthy young subjects.

BACKGROUND: Invasive studies in middle-aged patients suggest an acute adverse haemodynamic effect of smoking. AIMS: To study acute changes in blood pressure (BP), cardiac output, peripheral resistance and aortic compliance following cigarette smoking in healthy young subjects. METHODS: Using a non-invasive photoplethysmographic technique we compared the effects of smoking one cigarette with sham smoking in 12 healthy volunteers (22-25 years). Data was analysed using JMP version 5.0. RESULTS: In contrast to sham smoking there was a prompt increase in blood pressure with a maximum effect at 15 min (123 +/- 7/75 +/- 5 to 143 +/- 6/86 +/- 6 mmHg, mean +/- SEM, p < 0.01) which is attributed to a rise in cardiac output (p < 0.05) rather than changes in peripheral vascular resistance. There was also a significant (p < 0.05) increase in heart rate and a reduction in aortic compliance. CONCLUSION: These results suggest that healthor young age do not protect from the adverse effects of smoking.

Regional variation in prescribing for chronic conditions among an elderly population using a pharmacy claims database.

BACKGROUND: Age, gender and geographical regions are recognised factors in inequalities in prescribing for chronic diseases in the elderly. AIM: To compare the health board regional distribution of chronic disease among the elderly and to examine variation in quality prescribing across age, gender and regions. METHODS: Population based study of prescribing for chronic disease using a national pharmacy claims database. All individuals aged 70 years and over (n = 271,518) were eligible. RESULTS: Over 60% of the elderly in all regions received cardiovascular related medication. The South Eastern, North Western and Western Health Boards had below average prescribing for many chronic conditions. Logistic regression identified age, gender and regional variations in prescribing of preventative therapies for CVD and diabetes. CONCLUSION: There is a high prevalence of prescribing for chronic conditions in the elderly in Ireland, and there is evidence of gender, age and residing health board inequalities in prescribing.

Impact of Helicobacter pylori on the management of dyspepsia in primary care.

BACKGROUND: It is unclear what impact Helicobacter pylori infection has had on the management of dyspepsia in primary care and to what extent published guidelines on H. pylori are implemented in routine clinical practice. AIM: To assess the impact of H. pylori infection on the management of dyspepsia in primary care. METHODS: Patients referred by primary care doctors to an open-access 13-carbon urea breath test service over a 2-year period for their first urea breath test were included in the study. Individual breath results were linked with data on prescribing obtained from the General Medical Services prescription database. RESULTS: Of 805 patients, 374 (47%) had a positive urea breath test and 431 (54%) a negative urea breath test. Of positive urea breath test patients, only 245 (64%) were prescribed eradication therapy in the 3 months after the breath test and only 43% were referred back for re-testing. In the year after the urea breath test, there was a significant fall in prescribing of antisecretory therapy which was greatest in the patients who received H. pylori therapy (P < 0.001). CONCLUSIONS: There appears to be under and inappropriate treatment of H. pylori infection in primary care, and a low rate of re-testing after eradication, indicating that current guidelines are not well implemented in practice.

Prescribing for patients with diabetes in the community drug schemes.

The aim of the study was to examine the management of diabetes patients particularly in relation to secondary preventative therapies within the community drug schemes across the health board regions in Ireland. The study population was identified using two national primary care prescribing databases from the Long Term Illness (LTI) and General Medical Services (GMS) scheme for 2003. 65,593 patients were identified as having 'treated' diabetes. Logistic regression was used to predict the likelihood of receiving secondary preventative therapies by region and drug scheme using adjusted odds ratios (ORs) and 95% confidence intervals (CI). The proportion of diabetes patients in each drug scheme with Ischaemic Heart Disease (IHD) was also calculated. Prevalence of 'treated' diabetes was calculated for each health board also. Regional and scheme-based variations within each region exist in the prescribing of secondary preventative therapies after adjustment for IHD rates. Prevalence of treated diabetes varied between regions from 1.5% in the Eastern region to 2.2% in the Southern region. While the location of specialised diabetes clinics may be a contributing factor, inequalities in prescribing across regions within the drug schemes are apparent.

Adherence to clinical guidance in the prescribing of oral antithrombotic medication in patients with atrial fibrillation.

BACKGROUND: Atrial fibrillation is the commonest cardiac rhythm disturbance and is an independent risk factor for stroke; however, use of oral antithrombotic therapy is reported to be suboptimal in clinical practice. AIM: The aim of the study was to evaluate the prescribing rates of oral antithrombotic therapy in patients with atrial fibrillation to determine if prescribing patterns reflected published clinical guidance. METHOD: Patients with atrial fibrillation, admitted to hospital over a 12-week period were identified and their antithrombotic therapy regimen was analysed using statistical methods. RESULTS: Although 87/100 patients identified were prescribed OAT, the regimen was suboptimal in 35 patients. Patients aged 75 years and older were more likelyto be receiving suboptimal oral antithrombotic treatment compared with younger patients CONCLUSIONS: The benefits and suitability of oral antithrombotic therapy for patients of all ages need to be more comprehensively communicated to prescribers.

The population mortality benefits of maximizing the number of eligible patients receiving appropriate cardiology treatments in Ireland.

BACKGROUND: Coronary heart disease (CHD) mortality rates have been decreasing in many industrialized countries since the 1980s. Up to half this decrease can be attributed to evidence-based medical and surgical cardiology interventions. However, recent studies suggest that modern cardiology treatment uptake levels remain disappointingly low in many patient categories. AIM: To determine the potential for further reductions in CHD mortality in Ireland from increasing the number of eligible patients receiving cardiology treatments. METHODS: A previously validated, cell-based IMPACT CHD mortality model was used to integrate large amounts of data describing CHD patient numbers, and the effectiveness and uptake levels of specific medical and surgical treatments. The CHD mortality reductions potentially achievable through the increased use of specific treatments were then calculated, stratified by age and gender and tested using sensitivity analyses. RESULTS: In 2000, medical and surgical coronary disease treatments together prevented or postponed approximately 1950 CHD deaths in the adult population aged 25-84. However, increasing treatment levels to reach 80% of eligible patients might have prevented or postponed a further 2280 CHD deaths in 2000 (minimum estimate 860, maximum estimate 4000). The biggest gain was from maximizing the treatment uptake of eligible heart failure patients, followed by those receiving statins and secondary prevention therapies. DISCUSSION: Many eligible patients are currently not receiving appropriate evidence-based treatments that would reduce CHD mortality and morbidity. Our results suggest that increasing cardiology treatment uptake in Ireland could at least double the current therapeutic reduction in CHD mortality.

Socioeconomic influences on benzodiazepine consumption in an Irish Region.

Misuse of prescription sedatives is a significant problem for addiction treatment services. The aim of this study was to examine the prescribing of diazepam in disadvantaged Irish communities, and to identify factors which may predict diazepam consumption in that population. We examined prescribing trends for those aged 16-69 years in 2002 in a region of the state-funded General Medical Services Scheme. Material deprivation was based on the 2002 Small Area Health Research Unit (SAHRU) deprivation index. The average defined daily dose (DDD) was calculated and logistic regression analysis was used to predict diazepam use by age, gender and deprivation index. Results showed that patients living in the most-deprived areas were more likely to receive diazepam than patients living in the least-deprived areas (OR = 1.21, 95% CI 1.15-1.27). Female patients living in the most-deprived areas were also more likely to receive diazepam than those living in the least-deprived areas (OR = 1.36, 95% CI 1.18-1.57). It is concluded that there is a pattern of higher diazepam prescribing in areas of greatest deprivation, where prescription sedatives play a complex role within troubled families.

Collagen type-I degradation is related to arterial stiffness in hypertensive and normotensive subjects.

Although arterial stiffness is an independent cardiovascular risk factor associated with both aging and hypertension, relatively little is known regarding the structural changes in the vessel wall that occur with vessel stiffening. We determined if collagen type-I metabolism is related to arterial stiffening in both hypertensive and normotensive subjects. Arterial stiffness was assessed by aortic pulse wave velocity (PWV) and augmentation index (AIx) in 46 subjects (48.7 +/- 2 years, 32 hypertensives) and related to circulating markers of collagen type-I turnover. Collagen synthesis was assessed by the measurement of carboxy-terminal peptide of procollagen type-I (PIP) and collagen degradation by the measurement of carboxy-terminal telopeptide of collagen type-I (ICTP), by quantitative immunoassay. Matrix metalloproteinase-1 (MMP-1) and the tissue inhibitor of metalloproteinase-1 (TIMP-1) were also quantified by immunoassay. The ratio of collagen type-I synthesis to degradation was negatively correlated with both PWV (P<0.05) and AIx (P<0.05), whereas plasma MMP-1 levels displayed a positive correlation with both PWV (P<0.01) and AIx (P<0.01), after adjustment for age and mean arterial pressure. The relationship between collagen type-I turnover and arterial stiffness was similar in both the normotensive and hypertensive subjects. Although circulating markers of collagen synthesis were increased in the hypertensive subjects, this was not related to arterial stiffness. Collagen type-I degradation is increased in relation to collagen type-I synthesis in subjects with stiffer arteries. Matrix metalloproteinase-1, the enzyme responsible for collagen type-I degradation, is positively related to both large elastic and muscular artery stiffness in normotensive and hypertensive subjects.

Effect of clinical trial publicity on HRT prescribing in Ireland.

OBJECTIVE: To evaluate the effect of publicity surrounding the Women's Health Initiative (WHI) and Million Women (MW) studies on prescribing of all hormone replacement therapy (HRT) preparations and bisphosphonates in Ireland. METHODS: The General Medical Services (GMS) prescription database was used to identify the study population. Prescriptions were identified for HRT and bisphosphonate preparations [using WHO Anatomical Therapeutic Chemical (ATC) classification codes] in female patients aged 45-69 years in Ireland during a 4-year study period (January 2001-December 2004). Prescription rates were calculated monthly. Prevalence and incidence of HRT use was examined. RESULTS: There was a significant reduction in prevalence for all HRT preparations following the WHI trial (test for change in trend p<0.0001), which persisted after the MW study. The incidence of combined oestrogen/progestogen HRT declined after the WHI trial (test for change in trend p=0.004). Bisphosphonate prescribing showed a significant increase throughout the study period (p<0.0001). CONCLUSION: The findings suggest that coverage surrounding the publication of clinical trials appears to have had a negative impact on the rate of HRT prescribing. The findings regarding the coincident increase in use of bisphosphonates may suggest that prescribers and users were less likely to regard HRT as an appropriate therapy in the management of osteoporosis for some time before guidance was issued by the regulatory authorities.

Changes in prevalence of and prescribing for ischaemic heart disease in Ireland 1990-2002.

BACKGROUND: Secondary prevention therapies, such as angiotension converting enzyme (ACE) inhibitors, beta-blockers and statins, are known to reduce cardiovascular morbidity and mortality. OBJECTIVE: The aim of the study was to examine the prevalence of coronary heart disease (CHD) and the prescribing of secondary preventive therapies in the period 1990-2002. METHODS: The General Medical Services prescription database was used to identify the study cohort, those with CHD, in each year 1990-2002. CHD was defined in two ways: prescription of any nitrate, and co-prescription of nitrate and aspirin. In addition, co-prescription of secondary preventive agents including statins, ACE inhibitors and beta blockers were examined. RESULTS: We found a significant increasing prevalence of CHD from 1990 to 2002 in both men and women. There was a significant increase (p < 0.0001) in the prescribing rate for beta blockers, ACE inhibitors, and for statins, buta significant decrease (p < 0.0001) for calcium channel blockers. CONCLUSION: These trends reflect the growing evidence base on the effectiveness of secondary preventive therapies, and the implementation of the National Cardiovascular Health Strategy.