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Biomedical subjects

John Feely

Publications and source records attributed to John Feely.

34 records · Page 2Linked to original sources
PubMed2004

Have COX-2 inhibitors influenced the co-prescription of anti-ulcer drugs with NSAIDs?

AIMS: To quantify usage of COX-2 inhibitors compared with nonselective NSAIDs and to determine their impact (including financial) on the co-prescription of antipeptic ulcer (anti-PU) drugs. METHODS: The Irish General Medical Services prescription database (covering 1.2 million people) was examined for NSAID prescriptions during December 1999-November 2001. NSAID users were excluded during the first 6 months. During the next 12 months (study period) patients on NSAIDs (>or= 3 prescriptions) were identified. The study period and final 6 months provided data on co-prescription of anti-PU drugs. Age, gender, number of concomitant prescriptions, co-prescribing of anti-PU drugs and monthly cost were evaluated for 8 NSAIDs (n= 4 non-selective NSAIDs and n= 4 COX-2 inhibitors) and odds ratios (OR) calculated using logistic regression. RESULTS: COX-2 inhibitors were prescribed more frequently in older, female patients and those receiving multiple medications. After adjustment for age, gender and polypharmacy, anti-PU drugs were prescribed more frequently with COX-2 inhibitors (OR = 1.31 (1.23,1.40)). COX-2 inhibitors were up to 10-fold more expensive, median monthly costs (including anti-PU drugs) ranging from Euros 34.61 (COX-2 inhibitors) to Euros 3.26 (nonselective NSAIDs). CONCLUSIONS: Since COX-2 inhibitors are associated with increased rates of co-prescription of anti-PU drugs and are more expensive than non-selective NSAIDs, these results suggest that the expected cost-savings with COX-2 inhibitors may not be occurring in practice.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2004

Pseudo-hypertension and arterial stiffness: a review.

Hypertension is a condition of persistently elevated blood pressure, associated with increased cardiovascular risk. Non-invasive BP measurement using Korotkoff sounds is the most common method of screening for the condition. The possibility of inaccurate readings leading to a false diagnosis of hypertension (pseudo-hypertension) is of concern. Stiffened arteries in the elderly have been proposed as being the primary cause of pseudo-hypertension. Non-invasive detection of pseudo-hypertension remains problematic. This paper reviews clinical literature on pseudo hypertension and approaches to measuring the compressive stiffness of arteries, as well as biomechanical literature regarding models of arterial stiffness and the origin of Korotkoff sounds. Models of the latter show the importance of the relationship between transmural pressure and cross-sectional area (P1/Csa curve) of the brachial artery as it closes under the influence of the pressure cuff. The review concludes that future research on pseudo-hypertension should include development of new instrumentation to measure the P1/Csa curve of the brachial artery in vivo using non-invasive techniques suitable for application to an elderly population.

Animals↗
PubMed2004

Influence of socioeconomic status on the quality of prescribing in the elderly -- a population based study.

AIMS: To compare the quantity and quality of prescribing, using prescribing indicators, between the relatively deprived and the relatively affluent patients over 70 years old in primary care. METHODS: We examined the General Medical Services (GMS) scheme prescribing data for the Eastern region in Ireland for all patients aged 70 years or more (n = 95 055) during July 2001-December 2002. Prescribing indicators applied to the prescription data to evaluate drugs prescribed to each patient were classified as: (1) descriptive, e.g. number of drug items/patient; (2) indicators assessing potentially harmful prescribing; (3) evidence-based indicators, e.g. secondary prevention therapy in those with ischaemic heart disease (IHD). Results are expressed as odds ratio (OR) and 95% confidence intervals for comparison of prescribing between the relatively deprived and affluent cohorts, adjusted for age and gender (CI) using logistic regression analysis. RESULTS: The relatively deprived cohort was more likely to receive a greater number of drugs (5.2 vs. 4.5, P < 0.0001), more generic products (P = 0.01) and be exposed to major polypharmacy (> or = five drugs) compared with monotherapy (OR = 1.58; 95% CI = 1.52,1.64, P < 0.0001). They were more likely to receive potentially harmful drugs such as cerebral vasodilators (OR = 1.52; 1.38,1.69), long-acting sulphonylurea (OR = 1.43; 1.20,1.72), potentially interacting agents such as angiotensin converting enzyme (ACE) inhibitor and potassium sparing diuretic (OR = 1.78; 1.48,2.15). In terms of evidence-based prescribing, the relatively deprived cohort with IHD was less likely to receive secondary prevention therapies such as statins (OR = 0.82; 0.74, 0.90) and beta blockers (OR = 0.85; 0.77,0.93). CONCLUSIONS: These results show that suboptimal prescribing is more prevalent among the relatively deprived cohort and suggests the differences observed in the quality of prescribing between these patient groups may be related to their socioeconomic status.

Aged↗
PubMed2004

Prescribing for osteoporosis following the use of inhaled and oral glucocorticoids in general practice.

AIMS: Systemic absorption from inhaled glucocorticoids may lead to bone loss. We determined the extent to which their use alone and in addition to short courses of oral glucocorticoids was associated with increased prescribing for osteoporosis in a large general practice population. METHODS: In a cohort study with follow-up of co-prescribing of antiosteoporotic drug therapy in the Irish national prescribing database (1.1 million people over 16 years), we identified 32 081 patients who received inhaled glucocorticoids alone during a 12-month period (following an identical lead-in period). We determined the odds ratio (OR), adjusting for age and gender for the co-prescription of bisphosphonates or other antiosteoporotic therapy with inhaled glucocorticoids by logistic regression. RESULTS: The adjusted OR (95% confidence interval) for co-prescribing of bisphosphonates and all inhaled glucocorticoids was 1.87 (1.71, 2.04); 1.58 (1.41, 1.78) for inhaled beclomethasone, 2.11 (1.75, 2.54) for inhaled budesonide and 3.29 (2.65, 4.1) for inhaled fluticasone. The ORs were significantly increased when patients who also received oral glucocorticoids were included and greater still in those under 45 years: 14.03 (10.6, 18.6). The results remained significant when the effects of comorbidity were adjusted for. The odds of receiving bisphosphonate therapy increased linearly with increasing exposure to inhaled glucocorticoids during the study period. CONCLUSIONS: Treatment with inhaled glucocorticoids in general practice is associated with an increased risk of co-prescribing for antiosteoporotic therapy in a potency- and a dose-related manner. Exposure to a course of oral glucocorticoids doubles this risk. These results suggest that the systemic effects on bone mineral density from using inhaled glucocorticoids may be clinically relevant but may also reflect prescribers' concerns for the development of osteoporosis in these patients.

Administration, Inhalation↗
PubMed2004

Arterial stiffness and the renin-angiotensin-aldosterone system.

Arterial stiffness has recently been recognised as an independent risk factor for cardiovascular morbidity and mortality in hypertension. Many of the complications seen with angiotensin II (Ang II) excess or hyperaldosteronism--an increased event rate, left ventricular hypertrophy, endothelial dysfunction and target organ damage--are also associated with arterial stiffness. It is possible that reduced arterial compliance may be one mechanism whereby increased activity of the renin-angiotensin-aldosterone system (RAAS) produces adverse vascular effects. Common pathophysiological processes, altered collagen turnover and increased fibrosis may underlie both arterial stiffness and RAAS-associated vascular damage. While it is recognised that patients with hyperaldosteronism have increased arterial stiffness, the role of the RAAS in modulating arterial compliance in essential hypertension and in normotensive subjects is less clear cut. There is, however, more consistent data which show that drugs that interfere with Ang II or aldosterone, namely angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and aldosterone antagonists, all reduce arterial stiffness. In many cases, this is to a greater extent than predicted from the extent of reduction in blood pressure (BP), suggesting a role for RAAS in vascular stiffness in hypertensive subjects. There is also evidence that combined ACE inhibitors (ACE-Is) and ARBs may have an additive effect in reducing stiffness. The reduction in cardiovascular mortality in end-stage renal disease patients treated with ACE-Is was preferentially seen in those who had reduced arterial stiffness. These data suggest that, in addition to regulation of vascular biology and BP, the RAAS is an important determinant of arterial stiffness in health and, more particularly, in disease.

Aldosterone↗
PubMed2003

"Selective" switching from non-selective to selective non-steroidal anti-inflammatory drugs.

BACKGROUND: Non-steroidal anti inflammatory drugs (NSAIDs) are thought to account for almost 25% of all reported adverse drug reactions, primarily gastrointestinal (GI) toxicity. Selective cyclo-oxygenase-2 (COX-2) inhibitors have been shown to preferentially inhibit activity of the COX-2 enzyme, which maintains anti-inflammatory activity but reduces GI toxicity. OBJECTIVE: To determine the degree of switching from non-selective NSAIDs to COX-2 inhibitors and to examine the factors that were associated with switching. METHODS: The General Medical Services prescription database (1.2 million people) was examined for NSAID prescriptions from December 1999 through November 2001. All those receiving non-selective NSAIDs and those switching to selective COX-2 inhibitors after at least 1 month on a non-selective NSAID were identified (non-switchers and switchers, respectively). Age, sex, dose of non-selective NSAID and co-prescribing of anti-peptic ulcer (anti-PU) drugs were considered between switchers and non-switchers, and odds ratios (OR) calculated using logistic regression. The effect of chronic use (> or =3 months prescription of a non-selective NSAID during the study period) on switching was also evaluated. RESULTS: A total of 81,538 of 480,573 patients (17%) initially prescribed non-selective NSAIDs were switched to COX-2 inhibitors during the study. The elderly (65 years or older) were more likely to be switched to a COX-2 inhibitor [OR=1.81, 95% confidence interval (CI) 1.79, 1.84]. Women were also more likely to be switched to COX-2 inhibitor therapy (OR=1.25, 95% CI 1.23, 1.27). Previous but not subsequent prescribing of anti-PU drugs was also associated with switching. Chronic users showed similar switching patterns. CONCLUSIONS: Prescribers are more likely to switch older female patients and those with a past history of peptic ulcers from non-selective NSAIDs to COX-2 inhibitors. This suggests that doctors take risk factors into consideration when prescribing NSAIDs. The relatively low rate of switching may suggest that prescribers still have concerns over the place of COX-2 inhibitors and reserve their use to those patients particularly at risk of NSAID-induced GI toxicity.

Age Factors↗
PubMed2003

Spurious systolic hypertension of youth: fit young men with elastic arteries.

BACKGROUND: We examined the role of high pulse pressure (PP) amplification in spurious systolic hypertension (SSH). METHODS: We recorded demographic characteristics, brachial blood pressure (BP) (Omron Model HEM-705 CP, Vernon Hills, IL), aortic BP, and arterial wave reflection (Sphygmocor, AtCor Medical, version 6.2, NSW, Australia) and PP amplification in 174 healthy medical students (87 male) and 22 young male hypertensive subjects. RESULTS: Eleven subjects had SSH (147 +/-2 v control 114 +/-1 mm Hg, mean +/- SEM,), normal aortic and brachial diastolic BP with an aortic pressure waveform that was normal in contour and amplitude. All were male, tall, nonsmokers, and active in sports, with slower heart rate, reduced arterial wave reflection (-8 +/- 3 v -0.7 +/-1) and enhanced PP amplification (31 +/-1 v 18 +/-1 mm Hg, P <.01. In contrast, male hypertensive subjects had reduced amplification (14 +/-0.9 mm Hg) and enhanced arterial wave reflection (17 +/-1.9). CONCLUSIONS: The SSH of youth, with raised brachial but normal aortic systolic BP, is commonly seen in tall men who are active in sports and are nonsmokers. It may be explained by the exaggerated first systolic peak in the brachial artery pressure waveform, which is due to very high PP amplification and low arterial wave reflection due to elastic arteries.

Adult↗
PubMed2003

Evidence for an age and gender bias in the secondary prevention of ischaemic heart disease in primary care.

AIMS: To determine if a gender or age bias exists in the prescription of important secondary preventive therapies for ischaemic heart disease in primary care. METHODS: We identified 15 590 patients with ischaemic heart disease on the basis that they received a prescription for nitrate therapy over a 1-year period (September 1999 to August 2000) from the Eastern Region of the General Medical Services scheme in Ireland (population of 334 031), which provides free health service to those eligible patients in primary care. Odds ratios (OR) for the prescription of aspirin, beta-blockers, statins, calcium channel antagonists and ACE inhibitors in women and in those aged> 65 years were determined. RESULTS: Female patients were less likely to receive a prescription for a beta-blocker [OR = 0.84, 95% confidence interval (CI) = 0.79, 0.89, P < 0.001], aspirin (OR = 0.72, 95% CI = 0.67, 0.78, P < 0.001), and ACE inhibitors (OR = 0.83, 95% CI = 0.78, 0.89, P < 0.001) compared with their male counterparts. However, women were more likely to receive anxiolytic benzodiazepines (OR = 1.71, 95% CI = 1.59, 1.85, P < 0.001) compared with their male counterparts. Elderly patients (aged> 65 years) were less likely to receive aspirin (OR = 0.92, 95% CI = 0.85, 0.99, P < 0.001), beta-blocker (OR = 0.66, 95% CI = 0.62, 0.71, P < 0.001) and a statin (OR = 0.5, 95% CI = 0.46, 0.53, P < 0.001). CONCLUSIONS: An age and gender bias exists in the prescription of important secondary preventive therapies in primary care that may lead to increased mortality from ischaemic heart disease in these groups.

Adrenergic beta-Antagonists↗
PubMed2003

Effect of smoking on arterial stiffness and pulse pressure amplification.

The brachial artery pressure waveform is abnormal in smokers, but the effect of smoking on the aortic pressure waveform in both smokers and nonsmokers, particularly in the younger population, is unknown. We compared the acute and chronic effects of smoking on large-artery properties in 185 healthy young smokers and nonsmokers (mean+/-SD, 22+/-5 years). We matched 41 chronic smokers for age, height, weight, and gender with 116 nonsmokers. The augmentation index, a measure of arterial wave reflection in the aorta, was measured by applanation tonometry (Sphygmocor). We also compared augmentation index, aortic pulse wave velocity (Complior), and blood pressure in 28 subjects (11 chronic smokers) before and for 15 minutes after smoking 1 cigarette (nicotine content, 1.2 mg). Although brachial blood pressure was not different, the aortic systolic blood pressure (101+/-8 versus 97+/-9 mm Hg) and augmentation index (0.7+/-13 versus -5.7+/-14) were higher (P<0.01) in chronic smokers than in nonsmokers, whereas aortic-brachial pulse pressure amplification was reduced (13.7+/-8 versus 17.7+/-5 mm Hg, P<0.01). These effects were seen in both male and female subjects. Acutely in both groups, smoking significantly increased (P<0.01) both brachial and aortic blood pressure, augmentation index, and pulse wave velocity. No changes were seen after sham smoking. This study shows an acute increase in arterial stiffness after smoking 1 cigarette in chronic smokers and nonsmokers. Higher aortic systolic blood pressure and greater arterial stiffness, in part due to reduced pulse pressure amplification and increased arterial wave reflection, suggest that the adverse hemodynamic effects have hitherto been underestimated in young chronic smokers.

Adult↗
PubMed2003

Antihypertensive drugs and arterial stiffness.

Arterial stiffness is recognized as an important determinant of outcome in the hypertensive population. Although pulse pressure is an indirect index more recently relatively simple non-invasive techniques to measure pulse wave velocity, particularly in the aorta and arterial wave analysis have been developed and applied to clinical trials. There are clear differences in the effects of antihypertensive drugs on these parameters and stiffness is becoming a therapeutic target in its own right.

Adrenergic beta-Antagonists↗
PubMed2002

Reduction in arterial stiffness with angiotensin II antagonist is comparable with and additive to ACE inhibition.

We measured the effects of angiotensin II blockade on arterial stiffness, augmentation index (AI%), pulse wave velocity (PWV), and blood pressure (BP) in 12 hypertensive patients (mean 49 +/- 11 years) in a 4-week, randomized, cross-over study comparing valsartan 160 mg/day with captopril 100 mg/day, with a 2-week washout period. Subsequently both therapies were combined. Reductions in PWV and AI% remained significant when corrected for BP. Combined therapy reduced PWV and AI% (P < .05) more than monotherapy, even when corrected for BP. The study shows that angiotensin receptor antagonists reduce arterial stiffness in hypertension comparable with and possibly additive to angiotensin converting enzyme inhibition.

Adult↗
PubMed2002

Divergent effect of acute and chronic alcohol on arterial stiffness.

To study the effects of alcohol on large artery function we measured arterial wave reflection in the aorta as augmentation index (AI%) by applanation tonometry in 324 subjects (18 to 86 years, 223 male). In eight subjects, when ingested acutely, red wine containing alcohol (0.8 g/kg), but not dealcoholized wine, reduced (P < .01) blood pressure (BP), pulse wave velocity, and AI%. Men with an excessive alcohol consumption (>21 units/week) had a higher AI% (12 +/- 2 v 5 +/- 2, P < .05) and BP, particularly aortic systolic, than did those with a lesser intake. This study suggests that alcohol when ingested acutely may reduce arterial stiffness, although alcohol when ingested chronically, in excess, increases it.

Adolescent↗
PubMed2002

Effect of angiotensin ii receptor blockade on arterial stiffness: beyond blood pressure reduction.

We compared the effect of losartan (50 mg/day) to hydrochlorthiazide (12.5 mg/day) on blood pressure (BP) and arterial stiffness in 11 untreated hypertensive patients aged 47 to 69 years in a 4-week single blind randomized crossover study with an intervening 4-week washout period. Both drugs produced a significant (P <.001) and similar decrease in brachial BP. Only losartan induced a significant decrease in arterial wave reflection (P <.0001), with a preferential reduction in aortic (P <.001) compared to brachial pulse pressure. Losartan also significantly increased pulse pressure amplification and reduced pulse wave velocity. These results suggest that an AT(1) receptor antagonist induces a BP independent decrease in aortic stiffness and arterial wave reflection.

Aged↗
PubMed2002

Pharmacokinetic-pharmacodynamic drug interactions with HMG-CoA reductase inhibitors.

The HMG-CoA reductase inhibitors (statins) are effective in both the primary and secondary prevention of ischaemic heart disease. As a group, these drugs are well tolerated apart from two uncommon but potentially serious adverse effects: elevation of liver enzymes and skeletal muscle abnormalities, which range from benign myalgias to life-threatening rhabdomyolysis. Adverse effects with statins are frequently associated with drug interactions because of their long-term use in older patients who are likely to be exposed to polypharmacy. The recent withdrawal of cerivastatin as a result of deaths from rhabdomyolysis illustrates the clinical importance of such interactions. Drug interactions involving the statins may have either a pharmacodynamic or pharmacokinetic basis, or both. As these drugs are highly extracted by the liver, displacement interactions are of limited importance. The cytochrome P450 (CYP) enzyme system plays an important part in the metabolism of the statins, leading to clinically relevant interactions with other agents, particularly cyclosporin, erythromycin, itraconazole, ketoconazole and HIV protease inhibitors, that are also metabolised by this enzyme system. An additional complicating feature is that individual statins are metabolised to differing degrees, in some cases producing active metabolites. The CYP3A family metabolises lovastatin, simvastatin, atorvastatin and cerivastatin, whereas CYP2C9 metabolises fluvastatin. Cerivastatin is also metabolised by CYP2C8. Pravastatin is not significantly metabolised by the CYP system. In addition, the statins are substrates for P-glycoprotein, a drug transporter present in the small intestine that may influence their oral bioavailability. In clinical practice, the risk of a serious interaction causing myopathy is enhanced when statin metabolism is markedly inhibited. Thus, rhabdomyolysis has occurred following the coadministration of cyclosporin, a potent CYP3A4 and P-glycoprotein inhibitor, and lovastatin. Itraconazole has been shown to increase exposure to simvastatin and its active metabolite by at least 10-fold. Pharmacodynamically, there is an increased risk of myopathy when statins are coprescribed with fibrates or nicotinic acid. This occurs relatively infrequently, but is particularly associated with the combination of cerivastatin and gemfibrozil. Statins may also alter the concentrations of other drugs, such as warfarin or digoxin, leading to alterations in effect or a requirement for clinical monitoring. Knowledge of the pharmacokinetic properties of the statins should allow the avoidance of the majority of drug interactions. If concurrent therapy with known inhibitors of statin metabolism is necessary, the patient should be monitored for signs and symptoms of myopathy or rhabdomyolysis and the statin should be discontinued if necessary.

Animals↗