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Biomedical subjects

A J McLean

Publications and source records attributed to A J McLean.

At least 19 recordsLinked to original sources
PubMed1992

Prospective audit of an aminoglycoside consultative service in a general hospital.

OBJECTIVE: To investigate the impact of the introduction of a consultative service on the use, efficiency of dosing and clinical toxicology of the aminoglycoside antibiotics, gentamicin and tobramycin, in a general hospital. METHODS: Two audits were conducted six months and 18 months after the introduction of the consultative service. The audits reviewed the use of drug assay services, the adequacy of drug administration (as measured by serum antibiotic concentrations), indications for prescription, adverse outcomes (by noting markers of nephrotoxicity) and the antibiotic sensitivity of Gram-negative pathogens. The results were compared with the results of an audit conducted before the consultative service was instituted. RESULTS: There was a significant (P < 0.001 by chi 2 test) increase in the use of assays, with drug assays performed in 67% (first audit) and 77% (second audit) of aminoglycoside courses compared with 48.2% in the pre-intervention audit. Sample timing was greatly improved, with more than 70% of the samples collected at the appropriate times. Assay wastage in terms of uninterpretable assay results decreased significantly (P < 0.001) from 42.9% of total assays to 6.3% at the first audit and 3.8% at the second audit. The percentage of assay results in the desirable range increased significantly (P < 0.001) from 39.1% to 71.9% (first audit) and 75.4% (second audit). Pharmacokinetic recommendations were made in 39.1% and 64% of all aminoglycoside courses during the first and second audits respectively, with clinician acceptance of dosage recommendations at 83.1% and 82.8% respectively. For aminoglycoside courses prescribed for therapeutic reasons, 97.9% (first audit, n = 325) and 98.6% (second audit, n = 280) of indications for use were judged as clinically appropriate. The incidence of suspected aminoglycoside-induced nephrotoxicity was reduced from 8.9% of patients to 1.6% (first audit, P < 0.001) and 2.4% (second audit). Bacterial sensitivity audits showed that the great majority of clinical isolates of target organisms (n = 3523, Year 1 and n = 3385, Year 2) were sensitive to gentamicin (92.2% and 91.5% respectively) and tobramycin (98.1% and 98.8% respectively); these aminoglycosides exceeded all alternative agents in effectiveness, including first and third generation cephalosporins. CONCLUSIONS: The overall results indicate that introduction of the consultative service had a positive impact on the effective use of aminoglycosides, with a marked decrease in clinical toxicity. These influences were shown to persist for at least 18 months. The availability of reliable predictive techniques to reduce toxicity allows active promotion of aminoglycosides as the agents of choice on grounds of efficacy and economy.

Blood Specimen Collection↗
PubMed1992

Human factors in rural road crashes.

An in-depth study of 79 vehicle crashes on rural roads in an area of about 100 km radius around Adelaide examined sociodemographic and psychophysiological characteristics of the drivers and riders involved. In many respects this sample of crashes was similar to a much larger number of police-reported crashes in the same area but included: relatively more crashes with severe or fatal injuries; more crashes on divided roads, on sealed roads and on curves; and more crashes involving trucks. Alcohol and lack of seat belt use were shown to be major problems in these rural crashes. The drivers and riders most strongly associated with these particular problems were males, in blue collar occupations and with limited education; they tended to be aged 30 years or more in the case of alcohol abuse, and were likely to be under 30 years in the case of restraint misuse. The attitudes of these drivers and riders, and other characteristics likely to have contributed to their involvement in a crash, are discussed. There is a need to develop specific and effective countermeasures to reduce drink-driving and increase seat belt wearing in rural areas.

Accidents, Traffic↗
PubMed1991

Measuring and modifying hospital drug use.

OBJECTIVE: Various methods are available to quantitate medicinal drug use in hospitals. These represent a hierarchy of clinical specificity, complexity and cost of acquisition. Similarly, various strategies and methods are available to modify prescribing patterns. The objectives of this study are to illustrate these processes of measurement of drug use and modification of prescribing patterns using specific examples derived from practice at three major Australian teaching hospitals over 15 years. DESIGN, SETTING, MAIN OUTCOME MEASURES: Methods to measure and modify drug usage in the three hospitals are outlined and 12 examples are presented by specific drug or drug category. Each example includes details of the methods used to detect inappropriate drug use (pharmacy purchases, pharmacy issues, prescription analysis, clinical record review, performance and outcome assessment), the intervention strategies used (re-educative, persuasive, facilitative, power), the methods employed to alter drug prescribing and the relative effectiveness and cost-efficiency of the interventions. RESULTS: Readily available, relatively cheap quantitative methods provide significant information and an efficient basis for planning definitive studies, and substantial modification of prescription patterns is possible through the strategic use of limited manpower and resources.

Algorithms↗
PubMed1991

Dosage adjustment and clinical outcomes of long-term use of high-dose tobramycin in adult cystic fibrosis patients.

A two-phase study was undertaken designed to investigate the impact of computer-aided drug monitoring on tobramycin concentrations and clinical outcomes in adult patients with cystic fibrosis. In phase one, a baseline (historical control) study of drug use patterns was performed. During the second phase, patients admitted for intravenous treatment with tobramycin for acute exacerbations of pseudomonal pulmonary infections were randomly allocated to one of two schedules. Group A patients had tobramycin dosage regimens decided by clinicians based on pre-existing protocols using serum tobramycin assay data determined three times weekly. Group B patients had dosage regimens determined by a computerized pharmacokinetic predictive program using both population-based pharmacokinetic parameter estimation and fitting of serum concentration-time data using Bayesian regression. The agreed therapeutic target was a peak serum tobramycin concentration of 8-10 mg/L and a trough concentration of 1-2 mg/L. There was a major difference between the two groups comparing the number of paired trough and peak concentrations within the target concentration ranges (group A-14%; group B-34.7%, chi 2 test, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Drink-driving in the general night-time driving population, Adelaide 1989.

A roadside breath alcohol survey was conducted by the NHMRC Road Accident Research Unit in 1989 to monitor the efficacy of random breath testing (RBT) by the police. A reduction of 40 per cent in the proportion of drivers above the legal blood alcohol limit of 0.08 g/100 ml was found to coincide with a marked increase in the level of publicity of police RBT operations. Other factors may also have contributed to these large reductions in illegal drink-driving but this result was similar to that observed in 1987 when a major increase in publicity was accompanied by an increase in the level of enforcement of RBT. Although the full effect of these reductions has diminished with time, there appears to have been a decrease in illegal drink-driving in Adelaide from 1983 to 1987 and again to 1989.

Adult↗
PubMed1991

A new method of breath testing the general driving population.

The efficacy of drinking-driving countermeasures can be assessed in several ways, including reported changes in attitudes and behavioral intent as well as changes in crash rates. However, few studies have examined the changes in actual drinking-driving behavior. A method of surveying the blood alcohol concentrations (BACs) of drivers, without either police intervention or disruption to traffic flow, was developed in South Australia. This method, which has been used successfully to test approximately 50,000 drivers, is described in detail.

Alcoholic Intoxication↗
PubMed1991

Clinical pharmacokinetics in patients with liver disease.

From considerations of hepatic physiology and pathology coupled with pharmacokinetic principles, it appears that altered drug elimination in liver disease may result from the following mechanisms: reduction in absolute cell mass, in cellular enzyme content and/or activity, in portal vein perfusion due to extrahepatic/intrahepatic shunting, or of portal perfusion of hepatocyte mass due to decreased portal flow or sinusoidal perfusion; increase in arterial perfusion relative to portal perfusion; preferential perfusion of the sinusoidal midzone and terminal zones by arterioles; potential for direct mixing of arterial blood within the space of Disse; reduced exchange across the endothelial lining; and impaired diffusion within the space of Disse. In general, oxidative drug metabolism is impaired in liver disease and the degree of impairment of oxidisation differs between drugs but correlates best with the degree of sinusoidal capillarisation, i.e. the degree of access of the drug from the sinusoid to the hepatocyte. Drug conjugation appears to be relatively unaffected by liver disease, whereas elimination by biliary excretion correlates best with the degree of intrahepatic shunting and not with sinusoidal capillarisation. As the latter should impair hepatocyte access of all compounds similarly, a potentially important mechanism could be impaired access of oxygen to hepatocytes as oxidative metabolism is much more sensitive to oxygen supply than are conjugation or biliary excretion. This suggests a potentially important therapeutic role for agents which increase the hepatic oxygen supply. Useful adjunctive strategies may also derive from the oxygen limitation hypothesis. Anaemia should be targeted as a critically important variable, as should oxygen-carrying capacity, i.e. modification of the smoking habit. Additionally, enzyme inducers such as barbiturates may be used if overriding hypoxic constraints are removed by oxygen supplementation. Agents likely to seriously compromise arterial perfusion of the hepatic vascular bed should be avoided, e.g. those causing postural hypotension or vasospasm. Vasodilators can be used to actively promote arterial perfusion. While the effect of liver disease on drug handling is highly variable and difficult to predict, there are well recognised principles for modifying dosage. These include halving the dose of drugs given systemically (or of low clearance drugs given orally) and a 50 to 90% reduction in the dose of drugs with a high hepatic clearance given orally. Changes in the pharmacodynamic effects of drugs (either alone or in addition to pharmacokinetic changes) can also be profound, and awareness of this possibility should be increased.

Humans↗
PubMed1990

Publicity, police resources and the effectiveness of random breath testing.

Random breath testing (RBT) of drivers by the police was introduced in South Australia in 1981 at a very low level of enforcement. As there was no lasting effect on illegal "drink driving" the resources devoted to RBT were increased in 1987. In the months after this change police doubled the number of drivers tested by RBT. Concurrent with this change in the level of enforcement of RBT was an extensive publicity campaign, which warned drinking drivers of their increased risk of detection by RBT units. A roadside breath alcohol survey, conducted in metropolitan Adelaide late at night to evaluate the effect of these changes, showed a 34% reduction in the proportion of car drivers detected with a blood alcohol concentration at or above the legal limit of 0.08 g/100 mL.

Alcohol Drinking↗
PubMed1990

Extradural haemorrhage in infancy and childhood. A review of 35 years' experience in South Australia.

One hundred and two paediatric cases of extradural haemorrhage (EDH) were treated in Adelaide, South Australia, during the period 1954-1988; 10 were infants (0-2 years) and 92 were children (2-14 years). There were 9 deaths (mortality 8.8%). Long-term disabilities severe enough to interfere with school and/or employment were seen in 8 (7.8%) survivors. This relatively low number of adverse outcomes is partly an expression of a low incidence (5.9%) of associated intradural haematomas and few high-velocity impacts due to vehicular accidents. There is reason to believe that the results of treatment have improved in the decade 1977-1988. We attribute this in part to early diagnosis by computed tomography (CT), but a contributory factor may be earlier referrals from country centres to a paediatric trauma centre and rapid transfer, by air or road, by medical retrieval teams.

Adolescent↗
PubMed1989

Prospective audit of aminoglycoside usage in a general hospital with assessments of clinical processes and adverse clinical outcomes.

A comprehensive, multiphasic review of gentamicin and tobramycin utilization was undertaken with audits of the microbiological sensitivity of Gram-negative pathogens; indications for the prescription of aminoglycoside agents; the utilization of assay services; the adequacy of clinical drug delivery by measures of serum antibiotic levels; and the assessment of adverse outcomes by markers of nephrotoxicity. The great majority of clinical isolates of target organisms (n = 4208) was more sensitive to gentamicin (96%) and to tobramycin (99%) than to all alternative agents, including first- and third-generation cephalosporin agents. A review of the indications for the prescription of aminoglycoside agents by clinical criteria showed that in 85.6% of 278 documented cases, the choice of agent was appropriate by clinical and microbiological criteria. In a substantial (77.6%) proportion of the 511 patients who were receiving therapeutic courses of an aminoglycoside agent, serum drug assays had been performed. Assay data could not be interpreted adequately in 52.6% of 3079 assayed cases as a result of inadequate data on administration regimens (39.7%) or sampling regimens (12.9%). Where sampling was documented adequately, there was extreme variation (zero to five hours) in post-dose sampling. In only 33.2% of cases could it be concluded unambiguously that the patients were receiving safer, adequate therapy for clinically significant infections, 5.6% of patients were receiving potentially toxic doses, and 8.6% of patients showed suboptimal concentration profiles. The majority of potentially toxic levels were associated with adverse effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminoglycosides↗
PubMed1989

Triplet state characteristics and singlet oxygen generation properties of anthracyclines.

The triplet states of adriamycin (Ad), daunomycin (D) and two daunomycin analogues, daunomycinone (Dc) and daunomycin N-trifluoroacetamide (DAc), have been studied using laser flash photolysis and pulse radiolysis techniques. Triplet lifetimes, molar absorption coefficients, energy levels and quantum yields have been obtained for Dc and DAc, and estimated for D and Ad. Time-resolved near-infrared singlet oxygen luminescence measurements have been carried out on D, Ad and 5-iminodaunomycin (5-ID) in 2H2O solution and Dc in benzene solution at room temperature. Singlet oxygen quenching by the water-soluble anthracyclines was observed and a second-order rate constant of approx. 10(8) M-1.s-1 obtained. Electron spin resonance experiments have demonstrated that D photoexcited at lambda less than or 365 nm gives rise to singlet oxygen as shown by its reaction with 2,2,6,6-tetramethyl-4-piperidone to give the corresponding nitroxyl radical. Although all the anthracyclines studied have the ability to photosensitize the formation of singlet oxygen, the quantum yields are very low (phi delta approximately 0.02-0.03), suggesting that these anthracyclines would be poor photodynamic sensitisers.

Acetamides↗