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Biomedical subjects

P G Davey

Publications and source records attributed to P G Davey.

At least 19 recordsLinked to original sources
PubMed1997

Demand for warfarin anticoagulation monitoring in Tayside, Scotland.

AIM: The aim of this study was to assess the demand for warfarin prescribing and monitoring, and to identify patients with atrial fibrillation who might benefit from warfarin therapy. The study was carried out in the population of Tayside, Scotland (400,000 people) using patient-specific dispensed prescribing and hospitalisation data from the Medicines Monitoring Unit at the University of Dundee. METHODS: The incidence and prevalence of digoxin and warfarin prescribing were calculated between 1989 and 1993. Patients dispensed digoxin in 1993 were assumed to have atrial fibrillation and they were stratified into high risk groups for an adverse thromboembolic event based on past medical history. The numbers of patients at high risk who were judged to be possible candidates for warfarin were calculated. RESULTS: The prevalence of warfarin prescribing is increasing in Tayside and is mainly for elderly patients. There were also many patients assumed to have atrial fibrillation who were at particularly high risk for an adverse thromboembolic event, who had no record of warfarin prescribing. Only 35% received warfarin. Even given the methodological limitations of this study, and the use of aspirin as an alternative prophylactic agent, it is likely that these patients have been a source of increased prevalence of warfarin prescribing since 1993 and will be in the future. Other indications for warfarin prescribing are also increasing. CONCLUSION: It is anticipated that there will be increasing demands for anticoagulant monitoring, which will need to be met either by increasing the capacity of existing clinics, or by increasing the role of primary care.

Aged↗
PubMed1996

Impact of glycopeptide therapy after hospital discharge on inpatient costs: a comparison of teicoplanin and vancomycin.

Data were collected prospectively from 59 patients receiving vancomycin and 20 patients receiving teicoplanin. The mean daily drug cost was 52.40 pounds for teicoplanin and 31.13 pounds for vancomycin; the 95% Confidence Intervals (CI) for the difference in mean drug costs varied between 14.40 pounds and 28.10 pounds in favour of vancomycin. Use of a loading dose of teicoplanin significantly increased mean daily drug costs if the duration of treatment was less than 10 days. Costs of preparation, administration and monitoring were consistently higher for vancomycin than for teicoplanin and inclusion of these costs reduced the difference in mean daily costs to 13.01 pounds (95% CI 6.10 to 19.90 pounds). In Dundee 11 of 20 patients who received teicoplanin had received some of their treatment after discharge from the hospital and a survey of UK hospitals confirmed that teicoplanin treatment after discharge is being used in a wide range of conditions. The median proportion of teicoplanin treatment in Dundee given after discharge was 28.4% for each patient who received the drug: the median proportion of non-inpatient therapy was 50% per patient of those who received any teicoplanin treatment after discharge. Assuming that teicoplanin costs 20 pounds per day more than vancomycin, use of teicoplanin implies an investment of 70.42 pounds to gain one hospital day through earlier discharge of patients receiving teicoplanin.

Adolescent↗
PubMed1996

Variation in postantibiotic effect of clindamycin against clinical isolates of Staphylococcus aureus and implications for dosing of patients with osteomyelitis.

Initial measurements of postantibiotic effect (PAE) were made by a standard laboratory method (exposure to 1 mg of clindamycin per liter for 1 h). The range of PAE for 21 strains of Staphylococcus aureus isolated from osteomyelitis patients was 0.4 to 3.9 h, which markedly exceeded the coefficient of variation for the method (6 to 19%). Exposure of S. aureus to three doses of clindamycin at 8-h intervals had no consistent effect on either PAE or MIC. The PAE was dependent on both concentration and duration of exposure to clindamycin: for example, the PAEs for one strain were 1.7 h after exposure to 1 mg/liter for 1 h, 2.4 h after exposure to 4 mg/liter for 1 h, and 5.9 h after exposure to 4 mg/liter for 3 h. Pharmacokinetic simulations showed that the dose required to maintain free serum clindamycin concentrations above the MIC was 300 mg 6 hourly after oral administration (95% confidence interval, 243 to 301 mg) and 1.2 g 6 hourly (95% confidence interval, 305 to 1,145 mg) after intravenous (i.v.) administration. The duration of PAE would have to be at least 2.4 h to allow an increase in the oral dose interval to 8 h or to allow i.v. administration of 300 mg 6 hourly. Additional PAE experiments were performed with the three strains for which PAEs are the shortest after exposure to 1 mg/liter for 1 h (0.4 to 1.2 h). The PAE for these three strains increased markedly to 4.4 to 6.7 h following exposure to 2 mg/liter for 6 h (to mimic the area under the concentration-time curve from 0 to 6 h after a 300-mg dose). These data suggest that oral clindamycin could be administered at 300 mg 8 hourly in the treatment of S. aureus infection, whereas the i.v. dose interval should be 6 h. These suggestions should be confirmed by performing clinical trials.

Administration, Oral↗
PubMed1995

Cost management in community-acquired lower respiratory tract infection.

Pharmacoeconomic analysis must determine a credible cost model, including healthcare-related, non-healthcare-related, and intangible costs, and must identify important treatment outcomes. Outcomes can be ranked in terms of their sensitivity to different treatments or weighted in terms of cost. Two recent studies of community-acquired lower respiratory tract infection have shown that inadequate treatment is a frequent cause of repeat visits to the physician's office, involving extra costs that could presumably be avoided by more effective first-line treatment. When economic data are to be incorporated into clinical trials, it is important to collect data outside as well as within the trial center and to concentrate on data likely to be of significance to the decision makers the trial is designed to influence. The best way of achieving internal validity in such trials is through randomization, which minimizes bias, chance imbalance, and confounding factors. The three major determinants of the cost-effectiveness of treatment are efficacy, the value attached to preventing treatment failure, and the accuracy of diagnosis. The latter is important because a drug can only benefit patients if they have the disease for which it is an effective treatment.

Anti-Bacterial Agents↗
PubMed1995

A patch clamp study of the effects of ciprofloxacin and biphenyl acetic acid on rat hippocampal neurone GABAA and ionotropic glutamate receptors.

The neurotoxic effects of 4-quinolones alone and in combination with certain non-steroidal anti-inflammatory drugs (NSAIDs) may be related to an interaction at GABAA and/or ionotropic glutamate receptors. In the present study, the effects of the fluoroquinolone, ciprofloxacin, alone and in combination with the NSAID, biphenyl acetic acid (BPAA), were examined on GABAA-, NMDA-, AMPA-, and kainate-evoked current responses recorded from cultured rat hippocampal neurones, using the whole cell patch clamp technique. GABA-evoked currents were reversibly inhibited by bicuculline (3 microM) and ciprofloxacin (100 microM) to 11 +/- 5 and 38 +/- 7% of control, respectively. BPAA (100 microM) had little affect on the GABA current (the response was 82 +/- 4% of control) but enhanced the inhibitory potency of ciprofloxacin by approx. 3000-fold. The antagonist effects of ciprofloxacin (30 microM) and ciprofloxacin (0.03 microM) together with BPAA (100 microM) on the GABA-evoked current were not voltage-dependent. Whole cell currents evoked by NMDA, AMPA or kainate were little influenced by ciprofloxacin (100 microM), BPAA (100 microM), or ciprofloxacin plus BPAA (both at 100 microM); the responses being > or = 90% of control in all cases. These data suggest that the proconvulsant effects of quinolones when combined with BPAA may be related to antagonism of central GABAA receptors but not to an interaction at ionotropic glutamate receptors.

Animals↗
PubMed1995

Subspecies discrimination of staphylococci from revision arthroplasties by ribotyping.

Sixty-six cultures of Staphylococcus spp. were obtained from bone and tissue samples collected from 37 patients during revision arthroplasties and were speciated and ribotyped to assess strain diversity in each species. There were 10 ribotypes among 51 isolates of S. epidermidis, three among three isolates of S. capitis, two among four isolates of S. aureus and two among two isolates of S. simulans. One ribotype was found among each of: two isolates of S. warneri; two isolates of S. haemolyticus and single isolates of S. cohnii and S. saprophyticus. Low molecular weight bands of ribotype patterns characterized one or two related species whereas high molecular weight bands were useful for distinguishing types within species. Specimens from 17 patients yielded more than one isolate of Staphylococcus spp. In 13 of these patients the isolates were representatives of a single species but in only eight did ribotyping show the isolates to be identical. The findings of multiple species and ribotypes from samples taken from the same patient may have implications for understanding the nature of infection in revision arthroplasty and for antibiotic therapy.

Bacterial Typing Techniques↗
PubMed1995

The utilisation and economic evaluation of antibiotics prescribed in primary care.

This was an observational study of efficacy and resource utilisation over three years in a cohort of 917 patients who received at least one prescription for an oral antibiotic between January and March 1989 in a large rural primary care health centre in Tayside, Scotland. Three thousand, six hundred and sixty three prescriptions were issued (2286 to females) for; 1502 upper respiratory tract infections, 419 lower respiratory tract infections, 441 urinary tract infections, 177 skin and soft tissue infections, 97 gynaecological infections, 103 cases of acne and 71 other infections. Excluding acne, 14% of infections required more than one antibiotic to achieve a successful outcome. The highest success rates for antibiotics were amoxycillin (92%) and penicillin V (92%) in upper respiratory tract infections, erythromycin (90%) in lower respiratory tract infections and co-trimoxazole (83%) in urinary tract infections. The most cost-effective antibiotics were penicillin V for upper respiratory tract infection, erythromycin for lower respiratory tract infection and co-trimoxazole for urinary tract infection. Varying the value placed on general practitioners' time did not change the rank order of antibiotic cost-effectiveness. The efficacy and cost-effectiveness of the treatment of acute infections in primary care varies considerably with the antibiotic used as first choice. More expensive antibiotics might be justified in cost-effectiveness terms if they had high cure rates in clinical practice.

Adolescent↗
PubMed1995

Evaluation of an antibiotic prescribing protocol for treatment of acute exacerbations of chronic obstructive airways disease in a hospital respiratory unit.

A prescribing protocol for infective exacerbations of chronic obstructive airways disease (COAD), specifying the use of oral amoxycillin 500 mg tid (or erythromycin 500 mg qid if allergic) as first line therapy, and oral ciprofloxacin 500 mg bd as second line treatment, was introduced in 1991. Every third sequential admission was screened for the year preceding (1990) and the year after (1991) the protocol was implemented. Only those patients with a discharge diagnosis of infective exacerbation of COAD, but without pneumonia, were included in the analysis. The two groups (1990 and 1991) were matched in terms of age, sex and pre-treatment given by their General Practitioner (GP), but differed with respect to severity score, with 1991 being more severe. The outcome measures showed that duration of hospital stay was comparable as was duration of treatment. Response to first line therapy was 68% and 67% for 1990 and 1991, respectively. Of those who had received antibiotics from their GP, 67% responded to first line therapy, while of those who had not received antibiotics from their GP 75% responded. Duration of therapy was shorter in first line responders (mean and 95% CI: 7.3 (6.3-8.3) days vs 12.7 (10.1-15.3) days). The mean cost per day antibiotic treatment was reduced by 54.6% (95% CI 52.3-56.9%) from 3.77 pounds to 1.71 pounds. In conclusion, the introduction of antibiotic prescribing guidelines for treatment of infective exacerbations of COAD showed no detrimental effect on outcome measures, but was associated with a significant reduction in the cost of antibiotic therapy.

Anti-Bacterial Agents↗
PubMed1995

Prospective audit of costs and outcome of aminoglycoside treatment and of therapy for gram-negative bacteraemia.

The aims of this study were to audit the monitoring of aminoglycoside treatment to develop a method for measurement of the cost and outcome of treatment, and to assess the accuracy of a previously published sepsis score to predict cost and outcome. Measurements of costs and outcomes were also made for all patients (n = 85) with Gram-negative bacteraemia. Of these, 40 received an aminoglycoside and an additional 215 patients received aminoglycosides for other indications (total aminoglycoside patients 255; total patients 300). There were no interpretable assays for 82 (32%) of the aminoglycoside patients and only 33/173 (19%) patients assayed had first peak serum concentrations within the recommended range of 8-10 mg/L. Median costs of aminoglycoside treatment were 599 pounds in neutropenic patients, 471 pounds in ICU patients and 185 pounds in other patients. In the bacteraemic patients, median costs of aminoglycoside regimens (278 pounds) were higher than for non-aminoglycoside regimens (97 pounds). Death in hospital was twice as common in bacteraemic patients (20% versus 10%) and there was a stepwise increase in rate of mortality with sepsis scores. Treatment costs were markedly higher in patients who failed to respond to initial treatment, the mean difference in cost was 418 pounds per patient (95% CI 89 pounds - 747). Sepsis scores only explained 2.6% of the variance in treatment costs, and 22 patients with zero sepsis scores received prolonged courses of i.v. antibiotic treatment at an average cost of 209 pounds per patient. In conclusion, aminoglycoside regimens rarely conformed to accepted standards of care and treatment failure was associated with markedly increased treatment costs. Three readily measurable indicators of adverse outcome were identified (death in hospital, change of i.v. treatment and readmission within 2 weeks of discharge) and all were related to initial severity of illness as measured by sepsis score. The sepsis score may prove useful for assessment of individual risk but would benefit from further analysis to validate and possibly reduce the number of items in the score.

Adolescent↗
PubMed1994

Ciprofloxacin and sparfloxacin penetration into human brain tissue and their activity as antagonists of GABAA receptor of rat vagus nerve.

Patients undergoing elective surgery for removal of brain tumors, aneurysms, or other vascular malformations were administered a single oral dose of sparfloxacin (400 mg; 16 patients) or ciprofloxacin (750 mg; 5 patients) either 3 to 5 h or 22 to 26 h before surgery. Serum samples were taken from all patients at 0, 1, 3 to 5, 7 to 9, and 22 to 26 h after dosing; an additional serum sample was obtained at 48 h from patients who received sparfloxacin. A single sample of brain tissue was taken from all patients; a sample of cerebrospinal fluid (CSF) uncontaminated with blood was obtained from five patients. Serum and brain tissue samples were assayed by high-pressure liquid chromatography. Drug concentrations in brain tissue exceeded those in CSF by 1.8- to 19.4-fold. Kinetic modeling suggested that peak sparfloxacin concentrations in brain tissue may have occurred later than 3 to 5 h and that actual peak concentrations may therefore have been higher (up to 10 micrograms/g of tissue). The activities of ciprofloxacin and sparfloxacin as antagonists of the gamma-aminobutyric acid antagonist (GABAA) receptor were measured with the rat vagus nerve preparation. The 50% inhibitory concentration (IC50) of ciprofloxacin was 250 microM (95.25 micrograms/ml), but in the presence of biphenyl acetic acid (BPAA), the IC50 of ciprofloxacin was only 0.6 microM (0.23 microgram/ml). In contrast, the IC50 of sparfloxacin alone or in the presence of BPAA was > 300 microM (> 100 micrograms/ml). We conclude that the concentrations of ciprofloxacin and sparfloxacin in brain tissue may exceed serum drug concentrations and cannot be predicted from the concentrations in CSF. Sparfloxacin does not have any activity as a GABA antagonist, either alone or in the presence of BPAA, at the concentrations which are likely to be reached in human brain tissue.

Animals↗
PubMed1994

Assessing cost effectiveness of antimicrobial treatment: monotherapy compared with combination therapy.

The obvious costs of antibiotic treatment include drugs, equipment with which to give them, and assays. Less obvious, but more important, are the costs of quality control to ensure safe and effective treatment. The more complex the regimen, the more expensive the quality control. None the less, there is considerable variation in both assay price and number of assays/patient. Our data show that the drug costs of a regimen such as ampicillin plus gentamicin plus metronidazole are outweighed by the costs of quality assurance to prevent drug toxicity and charges of malpractice. Trials show that monotherapy with various beta-lactams is more cost effective than aminoglycoside combinations for surgical infections. Compounds such as piperacillin/tazobactam, a new beta-lactam/beta-lactamase inhibitor combination that is classed as monotherapy, have the potential to solve many of these economic problems. Several completed and continuing clinical studies are showing that monotherapy is as effective as combination treatment. Cost studies in the future are likely to confirm the economic advantages of monotherapy.

Anti-Bacterial Agents↗
PubMed1994

Cost-effectiveness of antibiotic prophylaxis of wound infection.

The estimated cost of a wound infection can vary substantially between countries and is dependent not only on the type of surgery performed, but also on varying medical practices and differing accounting methods. We therefore devised a flexible method to compare the cost-effectiveness of different antibiotic prophylactic regimens. Taking into account drug cost and the difference in infection rate between regimens, for any given wound infection cost, the analysis can indicate which regimen is most appropriate.

Amoxicillin↗
PubMed1993

Pharmacoeconomics of antimicrobial prophylaxis.

Pharmacoeconomic analysis of the prevention of infection is based on quantification of the benefits which result from prevention, rather than simple counting of the number of cases prevented. In general, benefits are best quantified as continuous variables which measure severity as well as occurrence, for example, cost of antibiotics prescribed is a useful continuous measure of severity to add to a discontinuous measure, such as number of patients who received antibiotics. Considerable progress has been made in the USA with the application of decision analysis to clarify the options available for dealing with a problem, the probability of good and bad outcomes for each choice and the utility which is associated with each outcome. These techniques deserve wide application. Much existing practice is based on limited, poor quality information about the occurrence and severity of infection. This situation can only be improved by wider application of standardized methods for definition of occurrence of infection and of underlying risk of infection.

Anti-Bacterial Agents↗