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Biomedical subjects

C P Denaro

Publications and source records attributed to C P Denaro.

At least 19 recordsLinked to original sources
PubMed2004

Towards more effective use of decision support in clinical practice: what the guidelines for guidelines don't tell you.

The Brisbane Cardiac Consortium Clinical Support Systems Program used multiple strategies in optimising quality of care of patients with either of two cardiac conditions. One of these strategies was the development and active implementation of decision support systems centred on evidence-based, locally agreed clinical practice guidelines. Our experience in undertaking this task highlighted numerous operational challenges for which solutions were difficult to extract from existing published literature. In the present article we provide a methodology grounded in both theory and real-world experience that may assist others in developing and implementing systems of guideline-based decision support.

Clinical Trials as Topic↗
PubMed2003

Quality of care of patients hospitalized with congestive heart failure.

BACKGROUND: Congestive heart failure (CHF) is an increasingly prevalent poor-prognosis condition for which effective interventions are available. It is -therefore important to determine the extent to which patients with CHF receive appropriate care in Australian hospitals and identify ways for improving suboptimal care, if it exists. AIM: To evaluate the quality of in-hospital acute care of patients with CHF using explicit quality indicators based on published guidelines. METHODS: A retrospective case note review was -performed, involving 216 patients admitted to three teaching hospitals in Brisbane, Queensland, Australia, between October 2000 and April 2001. Outcome measures were process-of-care quality -indicators calculated as proportions of all, or strongly -eligible (ideal), patients who received -specific interventions. RESULTS: Assessment of underlying causes and acute precipitating factors was undertaken in 86% and 76% of patients, respectively, and objective evaluation of left ventricular function was performed in 62% of patients. Prophylaxis for deep venous thrombosis (DVT) was used in only 29% of ideal patients. Proportions of ideal patients receiving pharmacological treatments at discharge were: (i) angiotensin--converting enzyme inhibitors (ACEi) (82%), (ii) target doses of ACEi (61%), (iii) alternative vasodilators in patients ineligible for ACEi (20%), (iv) beta-blockers (40%) and (v) warfarin (46%). CONCLUSIONS: Opportunities exist for improving quality of in-hospital care of patients with CHF, -particularly for optimal prescribing of: (i) DVT prophylaxis, (ii) ACEi, (iii) second-line vasodilators, (iv) beta-blockers and (v) warfarin. More research is needed to identify methods for improving quality of in-hospital care.

Aged↗
PubMed2002

Quality of care of patients hospitalized with acute coronary syndromes.

BACKGROUND: Measurement and improvement of quality of care is a priority issue in health care. Patients hospitalized with acute coronary syndromes (ACS) constitute a high-risk population whose care, if shown to be suboptimal on the basis of available research evidence, may benefit from quality improvement interventions. AIM: To evaluate the quality of in-hospital care for patients with ACS, using explicit quality indicators. METHODS: Retrospective case note review was undertaken of 397 patients admitted to three teaching hospitals in Brisbane, Queensland, Australia, between 1 October 2000 and 17 April 2001. The main outcome measures were 12 process-of-care quality indicators, calculated as either: (i) the proportion of all patients who received specific interventions or (ii) the proportion of ideal patients who received specific interventions (i.e. patients with clear indications and lacking contraindications). RESULTS: Quality indicators with values above 80% included: (i) patient selection for thrombolysis (100%) and discharge prescription of beta-blockers (84%), (ii) antiplatelet agents (94%) and (iii) lipid-lowering agents (82%). Indicators with values between 50% and 80% included: (i) timely performance of electrocardiogram (ECG) on admission (61%), (ii) early coronary angiography (75%), (iii) measurement of serum lipids (71%) and (iv) discharge prescription of angiotensin-converting-enzyme (ACE) inhibitors (73%). Indicators with values <50% included: (i) timely administration of thrombolysis (35%), (ii) non-invasive risk assessment (23%) and (ii) formal in-hospital, and post-hospital cardiac rehabilitation (47% and 7%, respectively). CONCLUSION: There were delays in performing ECG and administering thrombolysis to patients who presented to emergency departments with ACS. Improvement is warranted in use of non-invasive procedures for identifying high-risk patients who may benefit from coronary revascularization as well as use of serum lipid measurements, ACE inhibitors and cardiac rehabilitation.

Aged↗
PubMed2001

Lipid-lowering therapy following major cardiac events: progress and deficits.

OBJECTIVE: To assess hospital prescribing of lipid-lowering agents in a tertiary hospital, and examine continuation of, or changes to, such therapy in the 6-18 months following discharge. DESIGN: Retrospective data extraction from the hospital records of patients admitted from October 1998 to April 1999. These patients and their general practitioners were then contacted to obtain information about ongoing management after discharge. SETTING: Tertiary public hospital and community. PARTICIPANTS: 352 patients admitted to hospital with acute myocardial infarction or unstable angina, and their GPs. MAIN OUTCOME MEASURES: Percentage of eligible patients discharged on lipid-lowering therapy and percentage of patients continuing or starting such therapy 6-18 months after discharge. RESULTS: 10% of inpatients with acute coronary syndromes did not have lipid-level estimations performed or arranged during admission. Documentation of lipid levels in discharge summaries was poor. Eighteen per cent of patients with a total serum cholesterol level greater than 5.5 mmol/L did not receive a discharge prescription for a cholesterol-lowering agent. Compliance with treatment on follow-up was 88% in the group discharged on treatment. However, at follow-up, 70% of patients discharged without therapy had not been commenced on lipid-lowering treatment by their GPs. CONCLUSIONS: Prescribing of lipid-lowering therapy for secondary prevention following acute coronary syndromes remains suboptimal. Commencing treatment in hospital is likely to result in continuing therapy in the community. Better communication of lipid-level results, treatment and treatment aims between hospitals and GPs might encourage optimal treatment practices.

Adult↗
PubMed1998

Evaluation of pharmacokinetic methods used to estimate caffeine clearance and comparison with a Bayesian forecasting method.

Simplified pharmacokinetic methods have been used to estimate caffeine clearance in subjects with liver disease. There is a need to have a reliable, easy to implement method for research and possible clinical use. This study evaluates the use of Bayesian pharmacokinetic forecasting techniques to estimate caffeine clearance and compares its performance to other published methods. Commonly used published methods include the two-concentration overnight salivary clearance method (Jost method) and a method that samples caffeine concentrations over a 4-hour time period (Nagel method). Both have been used in studies incorporating serial measurements of caffeine clearance to predict clinical outcomes in subjects with liver disease, but these approaches have not been proven useful. However, neither method has been formally evaluated for accuracy in estimating caffeine clearance in subjects with cirrhosis. The performance of the Jost, Nagel, and Bayesian methods was compared to a Gold Standard method that accurately measured caffeine clearance in healthy subjects and subjects with cirrhosis using an intravenous infusion of stable isotope-labeled caffeine. The Bayesian method, even when only one measured concentration of caffeine was used, was more accurate, better correlated to the Gold Standard method, and had less intraindividual variation than the two previously published methods. Before the idea of using serial measurements of caffeine clearance for clinical usefulness is rejected, a reevaluation using methods of estimating caffeine clearance that are more accurate than previous paradigms is needed.

Bayes Theorem↗
PubMed1996

Validation of urine caffeine metabolite ratios with use of stable isotope-labeled caffeine clearance.

OBJECTIVE: A number of caffeine metabolite ratios have been proposed to measure CYP1A2 activity in vivo. The data to validate these ratios are scanty. The objective of this study was to validate urine caffeine metabolite ratios versus stable isotope-labeled caffeine clearance under different caffeine dosing conditions. STUDY DESIGN: Two experiments, one with nine nonsmoking subjects and the other with 12 cigarette smokers, were performed. We explored the relationship between caffeine clearance, measured by means of intravenous infusions of stable isotope-labeled caffeine, and a number of caffeine metabolite ratios during administration of different single or multiple doses of caffeine to smokers and nonsmokers on three different occasions over a 2-week period, using different durations of urine collections, including spot urines. The stable isotope technique allowed simultaneous oral dosing of caffeine and measurement of caffeine metabolite ratios and caffeine clearance, the latter reflecting CYP1A2 activity. RESULTS: The caffeine metabolite ratio of AAMU + 1U +1X/17U (5-acetylamino-6-amino-3-methyluracil + 1-methyluric acid + 1 methylxanthine/1,7-dimethyluric acid) maintained a significant correlation with caffeine clearance for all the above conditions (gamma2 range, 0.4 to 0.9) except for dose. With high doses of caffeine (12 mg/kg), a significant relationship was not observed. AAMU + 1U + 1X/17U also correlated with the formation clearance of paraxanthine (gamma2 = 0.6, p = 0.002). Other reported caffeine metabolite ratios did not display the same robust correlation with caffeine clearance under all these different conditions. CONCLUSIONS: We conclude that AAMU+1U+1X/17U measured from a single spot urine collection is a valid measure of CYP1A2 activity except at very high levels of caffeine dosing. The validity of the other proposed caffeine metabolite ratios is questionable.

Adult↗
PubMed1996

The effect of liver disease on urine caffeine metabolite ratios.

OBJECTIVES: A number of caffeine metabolite ratios (CMRs) have been proposed to measure CYP1A2 activity in vivo. The effect of liver disease on these ratios is not clear. The objective of this study was to determine the influence of liver disease on caffeine metabolite ratios. STUDY DESIGN: Two studies were performed. First, in healthy control subjects and in subjects with cirrhosis, caffeine clearance was measured by intravenous infusion of stable isotope-labeled caffeine while subjects consumed oral caffeine. Second, spot urine samples were collected from control subjects and from subjects with either chronic hepatitis or cirrhosis while they consumed caffeine. RESULTS: In study 1, caffeine clearance was decreased in subjects with cirrhosis (control mean, 0.14 L/hr/kg; cirrhosis mean, 0.04 L/hr/kg; p = 0.003). CMRs were affected by liver disease (e.g., ratio characterizing paraxanthine demethylation [AAMU + 1X + 1U/17U], control median, 8.3; cirrhosis median, 6.2; p = 0.005). AAMU + 1X + 1U/17U correlated significantly with caffeine clearance in the control group (r2 = 0.68; p = 0.0001) and in subjects with cirrhosis (r2 = 0.41; p = 0.05). In study 2, there was a significant difference between control subjects and subjects with cirrhosis for AAMU + 1X + 1U/17U (median for control subjects, 6.2; median for subjects with cirrhosis, 4.3; p = 0.001) but not between control subjects and patients with chronic hepatitis. CONCLUSIONS: We conclude that AAMU + 1X + 1U/17U is affected by liver disease and reflects the decrease in CYP1A2 activity in subjects with cirrhosis. AAMU + 1X + 1U/17U measured from a spot urine sample reflects caffeine clearance in subjects with cirrhosis and may be useful as a hepatic function test. Despite the large interindividual variation observed, the test can be repeated easily in the same patient and an individual patient's decline in CYP1A2 activity, such as in patients with progressively deteriorating liver function, can be monitored.

Adult↗
PubMed1993

Pharmacokinetic-pharmacodynamic modeling of caffeine: tolerance to pressor effects.

We propose a parametric pharmacokinetic-pharmacodynamic model for caffeine that quantifies the development of tolerance to the pressor effect of the drug and characterizes the mean behavior and inter-individual variation of both pharmacokinetics and pressor effect. Our study in a small group of subjects indicates that acute tolerance develops to the pressor effect of caffeine and that both the pressor effect and tolerance occur after some time delay relative to changes in plasma caffeine concentration. The half-life of equilibration of effect with plasma caffeine concentration is about 20 minutes. The half-life of development and regression of tolerance is estimated to be about 1 hour, and the model suggests that tolerance, at its fullest, causes more than a 90% reduction of initial (nontolerant) effect. Whereas tolerance to the pressor effect of caffeine develops in habitual coffee drinkers, the pressor response is regained after relatively brief periods of abstinence. Because of the rapid development and regression of tolerance, the pressor response to caffeine depends on how much caffeine is consumed, the schedule of consumption, and the elimination half-life of caffeine.

Adult↗
PubMed1991

Effects of caffeine with repeated dosing.

We have recently demonstrated dose-dependency of caffeine metabolism under multiple dosing conditions. Whether there are persistent pharmacodynamic actions of caffeine under such circumstances is the focus of this report. Nine healthy subjects were given, in randomized 5 day blocks, placebo, 4.2 (low) and 12 (high) mg.kg-1.day-1 of caffeine in 6 divided doses. After 5 days, complete tolerance developed to the effects of caffeine on blood pressure, heart rate and plasma glucose concentrations. The 24-h area under the curve (AUC) for plasma norepinephrine and the AUC for the total sum of free fatty acids (FFA) both demonstrated a trend to increase with the high dose caffeine treatment. When the AUC for norepinephrine was split into 12 h time periods, a significant difference between the placebo and the high dose treatment block was seen. We conclude that regular consumption of 12 mg.kg-1 of caffeine per day (equivalent to approximately 6 to 11 cups of coffee per day) may produce pharmacodynamic effects not completely compensated for by the development of tolerance. Mechanisms of tolerance may be overwhelmed by the nonlinear accumulation of caffeine and other methylxanthines in the body when caffeine metabolism becomes saturable.

Adult↗
PubMed1991

Stable isotope method for studying transdermal drug absorption: the nicotine patch.

A stable isotope-labeled drug method was used to determine the absolute bioavailability and absorption kinetics of a transdermal nicotine-delivery system (TTS). TTSs are being developed as an adjunct to smoking-cessation therapy. Deuterium-labeled nicotine was infused for 24 hours simultaneously to TTS application in cigarette-abstinent smokers. In 11 subjects with good patch adhesion, an average systemic dose of 19 mg nicotine was delivered, with average absolute bioavailability of 82%. The rate of nicotine absorption was maximal between 6 and 12 hours after TTS application and declined thereafter, plateauing between 16 and 24 hours at 62% of the maximal rate. Ten percent of nicotine was absorbed after the TTS was removed, demonstrating a reservoir for nicotine in the skin. Our study demonstrates the applicability of stable isotope methods in understanding the clinical pharmacology of transdermal drugs.

Administration, Cutaneous↗
PubMed1990

Dose-dependency of caffeine metabolism with repeated dosing.

Some recent epidemiologic studies have reported a nonlinear dose-response in the relationship between coffee consumption and health risks, such that the risks increase disproportionately to the increase in dose. Assuming caffeine contributes to the adverse health effects of coffee, a possible explanation for the nonlinear dose-response relationship is dose-dependent metabolism of caffeine. We examined the hypothesis that under chronic dosing conditions the metabolism of caffeine is dose-dependent. Nine healthy subjects were given, in randomized 5-day treatment blocks, placebo, 4.2 (low) and 12 (high) mg/kg/day caffeine in decaffeinated coffee, in six divided doses spaced throughout the day. On the third day of each dosing period, 25 mg of stable-isotope labeled caffeine (2-13C, 1,3-15N2) was given intravenously. Clearance of labeled caffeine fell from 0.118 (placebo treatment) to 0.069 (low dose; p less than 0.005) and to 0.54 (high dose; p less than 0.001) L/hr/kg. The formation and metabolite clearances of paraxanthine, the major primary metabolite of caffeine, also decreased comparing the low and high doses (p less than 0.05). We conclude that caffeine metabolism is dose-dependent, resulting in nonlinear accumulation of methylxanthines in the body. Dose-dependent metabolism of caffeine may explain in part why people who drink large amounts of coffee are at greater risk for cardiovascular disease.

Adult↗
PubMed1989

Comparison of Sawchuk-Zaske and Bayesian forecasting for aminoglycosides in seriously ill patients.

1. Individual pharmacokinetic parameters and predicted steady-state serum concentrations of aminoglycosides were calculated by Sawchuck-Zaske (SZ) and Bayesian methods. 2. Predicted concentrations were compared with observed steady-state concentrations for 36 seriously ill patients with systemic infections. Four aminoglycoside concentrations were used for the SZ method. Differing numbers of serum aminoglycoside samples were used in the Bayesian parameter estimation: one sample Bayesian used one post-infusion concentration, two sample Bayesian used a trough plus one post-infusion concentrations and four sample Bayesian used a trough plus three post-infusion concentrations. 3. 79% of the SZ predictions were with +/- 2 mg l-1 of the observed peak concentrations, and 72% of the two sample Bayesian predictions were within the same range. 82% of SZ and the two sample Bayesian predictions were within +/- 1 mg l-1 of the observed trough concentrations. 4. A confidence interval comparison of estimated pharmacokinetic parameters and precision for the predicted concentrations showed no important differences between the SZ and the two sample Bayesian. The four sample Bayesian was the most precise method. 5. We conclude that the Bayesian forecasting method utilizing a trough plus one post-infusion concentrations is as useful as the SZ method which requires three to four serum concentrations in individualizing aminoglycoside therapy for seriously ill patients.

Adolescent↗
PubMed1987

Usefulness of estimating individual pharmacokinetic data for aminoglycoside therapy in seriously ill patients.

This study proposes the use of individual pharmacokinetic parameters to predict effective dosages of aminoglycosides for patients with serious infections. Parameters were calculated for 51 patients using a one-compartment model. This model required a trough and three postinfusion aminoglycoside concentrations from each patient, as well as least squares linear regression. A total of 56 dosing regimens (37 gentamicin, 19 tobramycin) were predicted from these parameters and the efficacy of this approach was examined by comparing the predicted peak (8 mg/l) and trough (1.5 mg/l) concentrations with the observed peak and trough concentrations measured 24 h later. Aminoglycoside concentrations in serum were measured using a fluorescence polarisation immunoassay. Parameters varied widely, as the following ranges demonstrate: Volume of distribution 0.16-0.52 l/kg; clearance 0.04-0.17 l/kg/h; half-life 1.1-5.3 h. The doses predicted ranged from 3.2-16.9 mg/kg/day, with an average of 8.6 (standard deviation [SD] 3.4) mg/kg/day. The measured peak (mean 7.5; SD 1.6) and trough (mean 1.95; SD 0.57) concentrations closely approximated the predicted levels. The equations used underestimated trough concentrations mainly because of aminoglycoside accumulation. The changing pharmacokinetic parameters for each patient meant that regular drug assays were still required to fine-tune the dosing regimen. Two patients (4%) developed significant nephrotoxicity. Ototoxicity was not assessed. We conclude that individual pharmacokinetic data for aminoglycoside therapy can be used effectively to predict dosages for desired concentrations in seriously ill patients. The dose required was on average 1.5-2 times the normal recommended dosage.

Adolescent↗