PubMed HealthSearch

Biomedical subjects

M Feely

Publications and source records attributed to M Feely.

At least 19 recordsLinked to original sources

The influence of an academic representative on prescribing by general practitioners.

1. The effect of providing information about medicines by a short 'sales' interview between individual general practitioners and an 'academic representative' on prescribing was investigated. 2. The promotional campaign was designed to encourage a rational approach to prescribing of non-steroidal anti-inflammatory agents in an intervention group of 101 general practitioners selected at random from the Leeds Family Practitioner Committee (FPC). The remaining general practitioners in the Leeds FPC acted as a reference group. 3. The prescribing data for each group for 5 months immediately prior to and 5 months following intervention were compared. 4. Intervention produced a significant increase (P less than 0.005) in the prescribing cost of ibuprofen, the non-steroidal promoted as first choice agent, which was sustained for at least 5 months. 5. Prescribing of the second choice agent, piroxicam, decreased in the reference group but not in the intervention group. 6. There was a decrease in the average prescribing cost of pounds 6.60 per doctor per month in the intervention group compared with the reference group.

Costs and Cost Analysis

Comparison of lisinopril versus atenolol for mild to moderate essential hypertension.

The antihypertensive effects and safety profiles of lisinopril (10 to 40 mg) and atenolol (50 to 100 mg) were compared in a randomized, double-blind, parallel group trial in 144 patients with essential hypertension. After 8 weeks of therapy, seated blood pressure (BP) decreased by 26/15 mm Hg with lisinopril and by 19/14 mm Hg with atenolol. Lisinopril produced a greater reduction (p less than 0.05) in sitting systolic BP than did atenolol. Standing BP decreased by 25/15 mm Hg with lisinopril and by 19/14 mm Hg with atenolol. No important changes in hematologic and biochemical profiles were seen with either drug. Eleven patients, 7 receiving lisinopril and 4 receiving atenolol, were withdrawn because of adverse experiences; another 3 patients defaulted during treatment, 1 in the lisinopril group and 2 in the atenolol group. Both drugs were well-tolerated and are therefore suitable for first-line therapy in essential hypertension.

Antihypertensive Agents

Measuring compliance in methadone maintenance patients: use of a pharmacologic indicator to "estimate" methadone plasma levels.

A quantitative indicator of compliance is not available for methadone--the drug of choice for the treatment of opioid addiction. We successfully used low-dose phenobarbital (a valid pharmacologic indicator) to measure compliance by incorporating the drug into the methadone medication of patients attending an addiction unit. Plasma phenobarbital and methadone concentrations were measured in 20 (11 clinic-based and 9 community-based) patients receiving long-term treatment with the phenobarbital level-to-dose ratio, together with interviews, to validate methadone measurements and to monitor compliance. Patients attending the unit on a daily basis and who consumed their medication in the clinic were substantially more compliant than community-based patients. Laboratory measurements of phenobarbital and methadone helped to identify the use of illicit methadone, as well as incorrect self-administration, such as the consumption of several days' dosage at one time.

Adult

The prediction of steady-state plasma phenobarbitone concentrations (following low-dose phenobarbitone) to refine its use as an indicator of compliance.

1. A model for predicting the steady-state plasma concentration of phenobarbitone following low-dose phenobarbitone used as an indicator of compliance was derived using data for 10 healthy volunteers. 2. Each volunteer was given a single 30 mg oral dose of phenobarbitone and the pharmacokinetics were described. Subsequently, volunteers were given phenobarbitone 2 mg daily for 28 days and a further pharmacokinetic profile determined during and after this period. 3. An initial predicted estimate of steady-state plasma drug concentration was made using each volunteer's demographic details. This estimate was revised by Bayesian analysis using single timed samples (24, 48, 72 or 96 h) following the single dose. 4. The model was tested on a further 10 healthy volunteers given a single 8 mg dose and who were subsequently given 2 mg daily for 28 days. 5. The revised estimate of peak steady-state plasma phenobarbitone concentration utilising the 96 h post-single dose concentration (356 ng ml-1) was least biased (mean prediction error +/- 95% CI = 10.6 +/- 19.8 ng ml-1) and most precise (root mean square error +/- 95% CI = 28.3 +/- 19.0 ng ml-1). In all cases the peak or trough steady-state drug concentration was within 13% of the predicted value. 6. The model reflected compliance accurately in a further eight volunteers with simulated partial (two-thirds) compliance. 7. The use of a predictive model using Bayesian analysis to estimate expected steady-state plasma phenobarbitone concentrations could increase further the usefulness of low-dose phenobarbitone as an indicator of compliance.

Adult

What do patients and rheumatologists regard as an 'acceptable' risk in the treatment of rheumatic disease?

A questionnaire designed to ascertain the risk of adverse effects which patients with rheumatic conditions would accept for a particular therapeutic outcome was administered to 50 patients. The same questionnaire together with 'potted' histories of five of the patients was sent to 10 consultant rheumatologists. The willingness of both patients and doctors to risk side-effects varied with both the severity of the side-effect and the potential therapeutic benefit. Doctors were more willing than patients to risk death or serious disability (Wilcoxon, P less than 0.01) for a particular expected benefit. Doctors were also more willing to risk side-effects in treating seropositive rheumatoid arthritis than in treating non-articular rheumatism. No correlation was seen for patients between acceptable risk and diagnosis, pain or smoking habits. The risks which both groups stated they were willing to accept were less than those apparently associated with antirheumatic therapy. The results disagreed markedly with those of a previous study, demonstrating the importance of the methods used in this type of work.

Attitude of Health Personnel

A comparison of a short half-life marker (low-dose isoniazid), a long half-life pharmacological indicator (low-dose phenobarbitone) and measurements of a controlled release 'therapeutic drug' (metoprolol, Metoros) in reflecting incomplete compliance by volunteers.

1. Although, long half-life compounds appear to be more appropriate pharmacological indicators of compliance with treatment, short half-life markers or measurements of short half-life therapeutic drugs are frequently used. 2. We have compared the usefulness of low-dose phenobarbitone (a long half-life indicator), low dose isoniazid (a short half-life marker) and controlled release metoprolol (Metros) (a controlled release formulation of a short half-life 'therapeutic' drug) in seven volunteers with simulated partial (two thirds) compliance. 3. Detection of isoniazid metabolites in urine had an 83% sensitivity and 94% specificity for detecting ingestion within the previous 24 h and 100% sensitivity and 82% specificity for detecting ingestion within the past 6 h but gave no indication of the longer term pattern of compliance. 4. At 28 days (a time when steady-state would be obtained for all three drugs) phenobarbitone plasma levels were 70% (66-76%)--median and interquartile range--of the expected steady-state level if compliance had been complete. Corresponding figures for metoprolol were 82% (37-100%). 5. Measurement of phenobarbitone was much superior to isoniazid or metoprolol measurements in reflecting partial compliance over the previous 1 to 4 weeks.

Administration, Oral

Lack of anticonvulsant tolerance with RU 32698 and Ro 17-1812.

Possible development of anticonvulsant tolerance to three benzodiazepine receptor ligands was assessed in mice using an i.v. infusion of pentylenetetrazol as the convulsive stimulus. Extensive tolerance developed rapidly in the case of diazepam (0.35 mg/kg b.d. or 1.5 mg/kg b.d.). No significant tolerance was seen with the imidazopyrimidine derivative RU 32698 (9 mg/kg b.d.) or the partial agonist benzodiazepine Ro 17-1812 (1 mg/kg b.d.) These results provide further support for the hypothesis that partial agonists at the benzodiazepine receptor induce less tolerance than full agonists.

Animals

Time to stop counting the tablets?

We attempted to assess compliance using both a pharmacologic indicator (low-dose phenobarbital) and a return tablet count in 225 patients who were taking part in three separate studies. There were 216 patients (96%) who kept a follow-up appointment after 28 days; 161 patients appeared to have good compliance (90% to 109%) by return tablet count. Of these 161 patients, 51 (32%) had plasma phenobarbital concentrations (corrected for dose and weight) that were less than 90% of the lowest value previously found in normal volunteers, which suggested poorer compliance. When compared with the age-related volunteer values, 77 (48%) had values that were less than 90% of the lowest volunteer value. There were 6 of 10 patients with apparently excessive (greater than or equal to 110%) compliance by return tablet count and 4 of 12 who failed to return their container who also had phenobarbital concentrations that were less than 90% of the lowest volunteer value. We concluded that return tablet count grossly overestimates compliance.

Drug Therapy

Patients' knowledge concerning their medications on discharge from hospital.

Fifty patients were interviewed, on discharge from hospital, about their medications. Nine (18%) patients did not know, and a further four (8%) had inappropriate beliefs about why they were taking at least one of their discharge medications. Very few patients knew of significant side-effects which they might expect, or precautions which they should take, and over half did not know how long they were to continue taking their medicines. A small proportion was unable to read the bottle or open the container. Thus, even patients who, by virtue of an in-patient stay, have had a prolonged opportunity for education regarding their medicines have very little knowledge of their medicines upon discharge from hospital.

Drug Therapy

Compliance in clinical trials.

Compliance with treatment can be an important determinant of the outcome of clinical trials. To date there is no completely satisfactory method of measuring compliance and some of the most widely used methods are inadequate. The various methods of measuring compliance and how they have been applied to clinical trials are described, and improvements in the standard of the measurement and reporting of compliance in clinical trials are suggested.

Anti-Inflammatory Agents, Non-Steroidal

RO 16-6028, a benzodiazepine receptor partial agonist, does not exhibit anticonvulsant tolerance in mice.

The development of anticonvulsant tolerance with RO 16-6028, a benzodiazepine receptor partial agonist, was assessed in mice using an i.v. infusion of pentylenetetrazol as the convulsive stimulus. In contrast to other benzodiazepines tested previously in this seizure model the anticonvulsant protection afforded by RO 16-6028 did not change significantly during 10 days treatment (2 mg/kg b.i.d.). This result supports the hypothesis that partial agonists at the benzodiazepine receptor may induce less tolerance and/or dependence than full agonists.

Animals

Can benzodiazepines be classified by characterising their anticonvulsant tolerance-inducing potential?

The development of anticonvulsant tolerance with three benzodiazepines was assessed in mice using a slow intravenous infusion of pentylenetetrazol as the convulsive stimulus. Chlordiazepoxide (12.5 mg/kg b.d.) and midazolam (0.75 mg/kg b.d.) induced a slowly evolving tolerance over 15 days whereas nitrazepam (0.6 mg/kg b.d.) induced a very marked rapid tolerance which developed no further during 6 days treatment. Tolerance appeared to be incomplete with all three benzodiazepines. Possible explanations for the differences in tolerance profile are discussed and an alternative basis for the classification of benzodiazepines is suggested.

Animals

Use of a pharmacological indicator to monitor compliance with thyroxine.

Poor compliance with medication is often suspected, but difficult to confirm. The compliance of fourteen newly diagnosed hypothyroid patients was assessed using both TSH levels and low-dose phenobarbitone as a pharmacological marker. The study confirms the value of phenobarbitone as an indicator of compliance over a protracted period and suggests that it could be used to differentiate under-treatment from poor compliance.

Adult