Changes in the management of acute myocardial infarction in Southern Tasmania.

BACKGROUND: In recent years, the management of acute myocardial infarction (AMI) has been the subject of many clinical trials. These studies have clearly established the value of using pharmacological agents, including aspirin, beta-blockers, thrombolytics and angiotensin converting enzyme (ACE) inhibitors. There have been suggestions, however, that practice has been slow to change in light of the findings of these trials. AIM: To review cases of AMI at the major teaching hospital in Tasmania, Australia, to determine whether the recommendations from the results of the trials had been translated into local clinical practice, and to examine temporal changes in drug usage and clinical outcomes. METHODS: A retrospective review of the medical records of patients admitted to the hospital with an AMI during 1996 and for the first four months of 1998 was performed. An extensive range of demographic and clinical variables was recorded, and differences between the 1996 and 1998 patients and between recipients and non-recipients of the different pharmacological agents were statistically evaluated. RESULTS: The patients had a mean age of 65.9 +/- 12.3 years in 1996 (n = 205) and 66.8 +/- 12.3 years in 1998 (n = 71), with males accounting for 64.4% of cases in 1996 and 64.8% of cases in 1998. There were no significant demographic or medical history differences between the two groups. The median time of presentation after the onset of chest pain was 3.5 h in 1996 and 4 h in 1998. The rates of use of major therapeutic interventions post-AMI for 1996 and 1998, respectively, were: aspirin (89.1%, 90.3%), streptokinase (18.5%, 9. 9%), r-tPA (14.1%, 21.1%), intravenous beta-blockers (11.2%, 7.0%), oral beta-blockers (67.2%, 49.3%; P < 0.01), ACE inhibitors (44.4%, 59.2%; P < 0.05), intravenous nitrate (94.1%, 91.6%), oral nitrate (22.9%, 26.8%), calcium channel antagonists (19.5%, 35.2%; P < 0.05), cholesterol lowering agents (26.3%, 40.9%; P < 0.05), antiarrhythmics (21.5%, 25.4%) and warfarin (8.3%, 9.9%). Patients who received therapy with each of aspirin, r-tPA, intravenous beta-blockers, oral beta-blockers, intravenous nitrate and cholesterol lowering agents were significantly younger than the non-recipients (all P < 0.01), while patients treated with ACE inhibitors and antiarrhythmics were significantly older than the non-recipients (both P < 0.001). Non-recipients of thrombolytics presented to hospital significantly later, on average, than recipients. The hospital mortality rate was 15.1% in 1996 and 12.7% in 1998, and adverse drug reactions occurred in 21.5% of patients in 1996 and 15.5% in 1998. CONCLUSION: Although there have been substantial increases in the use of ACE inhibitors and cholesterol lowering agents post-AMI in recent years, reductions in the use of thrombolytics and beta-blockers and their possible underuse in the elderly are of concern and warrant intervention.

Review of antithrombotic drug usage in atrial fibrillation.

BACKGROUND: The important prophylactic role of antithrombotic therapy against stroke in nonrheumatic atrial fibrillation (AF) has been clearly established in recent clinical trials. There have been suggestions, however, that practice has been slow to change in light of the findings of these trials. AIM: To review cases of AF at the major teaching hospital in Tasmania, Australia, to determine whether the recommendations from the results of the trials had been translated into local clinical practice. METHODS: A retrospective review of the medical records for consecutive patients who had AF documented on ECG between 1 January and 30 June 1997 was performed. An extensive range of demographic and clinical variables were recorded for patients with chronic or paroxysmal nonrheumatic AF. These included antithrombotic and other drug therapy at admission and discharge from hospital care, risk factors for stroke, contraindications to antithrombotic use, and incidents of ischaemic stroke and bleeding complications that occurred during the period from January 1996 up to 3 months after the hospital admission that was studied. RESULTS: The 228 patients included in the study had a mean (+/-SD) age of 75.3+/-10.9 years. Sixty-eight per cent had chronic AF and 32% had paroxysmal AF. According to two risk stratification criteria, 91% and 86% of the patients with previously diagnosed chronic or paroxysmal nonrheumatic AF (n=186) had a high risk of developing stroke at the time of admission to hospital care. However, less than one-third of these patients were receiving warfarin (or warfarin plus aspirin), with almost another one-third receiving no antithrombotic agent. Of those who were not taking warfarin, about 60% had no apparent contraindication to warfarin. For those high risk patients who had a possible contraindication to warfarin, only approximately one-third had been prescribed aspirin. Only a slight increase in the use of antithrombotic agents had occurred by the time of discharge from hospital care. The majority of international normalized ratio (INR) values on admission for patients who had been taking warfarin were subtherapeutic. The estimated annual incidence of bleeding complications in patients taking warfarin was 15.0% overall, 5.0% for major bleeds and 3.8% for intracranial haemorrhages. CONCLUSIONS: While a number of published trials have demonstrated that antithrombotic agents confer substantial protection against stroke in patients with nonrheumatic AF, the drugs were underused in our setting. There is a need to improve antithrombotic use and to develop a better monitoring system for the provision of safer and more effective antithrombotic therapy.

Case-controlled review of Clostridium difficile-associated diarrhoea in southern Tasmania.

AIM: While the incidence of Clostridium difficile-associated diarrhoea (CDAD) has increased sharply over the last 15 years, its risk factors are still not well defined. The aim of this study was to review cases of CDAD at the major teaching hospital in Tasmania, Australia, to identify risk factors for CDAD and their association with prognosis. METHODS: A retrospective review of the medical records of adult patients admitted to the hospital between January 1994 and December 1996 was performed. Sixty-four patients who developed CDAD prior to or during their admission, and an additional 120 diarrhoea-free patients (the control group) were studied. An extensive range of demographic and clinical variables were recorded, and the differences between the control group and patients with CDAD were evaluated. RESULTS: The CDAD patients had a median age of 66 years (range 22-95 years), with females accounting for 52% of cases. There were no significant demographic differences from the control group. Identifiable risk factors for developing CDAD were severe underlying disease, renal impairment, exposure to antibiotics or antineoplastic agents, and the use of total parenteral nutrition or nasogastric feeding. Cephalosporins were the most frequently used antibiotics in both CDAD and control patients, with cefotaxime being the only antibiotic which was identified as being significantly associated with an increased risk of CDAD. The median length of diarrhoea episodes was 9 days (range 1-60 days). The mortality rate was 17.2%, and factors associated with a poor prognosis were older age, severe underlying disease, renal impairment and failure to treat with metronidazole or vancomycin. Delay in starting specific treatment and use of codeine were related to prolonged CDAD. CONCLUSION: CDAD is a growing contributor to hospital morbidity and costs. Severely ill patients with compromised immune function are particularly susceptible, with antibiotic use being a major risk factor. Prompt diagnosis and initiation of treatment are important factors in the improvement of prognosis.

An investigation of pain experience and management following gynecological day surgery: differences between open and closed surgery.

This study aimed to investigate the pain and activity levels of patients for a 5-day period following gynecological day surgery. Patients recorded their degree of pain and activity on visual analogue scales in a diary; completed diaries were returned by 54.9% of the patients approached (106 of 193). The median age of the women was 28.5 years (range, 15-55 years). Each procedure was classified as either open or closed surgery, depending upon whether an incision was necessary. Most (63.2%) of the patients required analgesics on the first morning after their surgery. Open surgery patients experienced significantly more pain for at least 3 postoperative days and were less active until the fifth day (P < 0.05 by Mann-Whitney tests). Drowsiness (47.2%), nausea (30.2%), and headache (30.2%) were the most common adverse effects experienced in the first postoperative morning. The incidence of adverse effects declined over the five days, but a minority of patients still suffered with headache (14.2%), drowsiness (9.4%), sore throat (7.5%), and nausea (5.3%) on the fifth day following surgery. The percentage of patients who experienced constipation peaked at 19.8% on the second day, most likely reflecting the consumption of codeine-containing analgesics on the first and second postoperative days. While day surgery has an important role in many forms of gynecological surgery, the potential discomfort and recovery time following day surgery should not be underestimated.

Psychoactive drug prescribing in the Tasmanian community.

OBJECTIVE: To gather data on the prescribing of psychoactive drugs (benzodiazepines, antidepressants and antipsychotics) using a network of Tasmanian community pharmacies. DESIGN SETTING AND PARTICIPANTS: The prescribing of psychoactive drugs in the community was studied during 1989 using data retrospectively obtained from computerised dispensing systems in 11 community pharmacies in Tasmania. The data collection procedure included all prescriptions dispensed in the pharmacies, irrespective of supply under the Pharmaceutical Benefits Scheme, the Repatriation Pharmaceutical Benefits Scheme or as a private prescription. MAIN OUTCOME MEASURES: Results of the pooled data were quantified by both the number of prescriptions and the defined daily doses (DDDs) dispensed for the psychoactive drugs. RESULTS: When extrapolated to the population of Tasmania, the estimated annual prescribing rates for the benzodiazepines, antidepressants and antipsychotics (including lithium) were 853.3, 316.2 and 54.8 prescriptions per 1000 persons, respectively. Prescriptions for the psychoactive drugs accounted for 13.2% of all prescriptions dispensed. In terms of DDDs, the estimated prescribing rates for the total Tasmanian population for the benzodiazepines, antidepressants and antipsychotics were 47.8, 12.5 and 2.1 DDDs per 1000 persons per day, respectively. The rate of benzodiazepine prescribing appeared to be high in comparison with the limited Australian data available. The relative prescribing rates of the long acting benzodiazepine hypnotics, flunitrazepam and nitrazepam, were also disturbingly high. CONCLUSIONS: This study has demonstrated the potential value of comprehensive pharmacoepidemiological data obtained from a network of community pharmacists and will form the basis for future studies using an expanded collection procedure.

Salicylate pharmacokinetics in patients with rheumatoid arthritis.

1. The pharmacokinetics of salicylic acid (SA) and its major metabolite salicyluric acid (SU) were studied in nine patients with rheumatoid arthritis following a 900 mg oral dose of acetylsalicylic acid and during 6 weeks of chronic administration of enteric coated aspirin (3,900 mg day). Response to therapy was also monitored. 2. The various pharmacokinetic parameters determined in the study were similar to those observed in other single dose salicylate studies amongst healthy volunteers but were not predictive of salicylate concentration in the chronic dose study. 3. Plasma concentrations of SA (total and unbound) were found to decline significantly over the 6 weeks and plasma SU concentrations increased. 4. During the chronic dosing study, there was a significant increase in the Vmax (total and unbound) for the formation of SU, whilst the Km and SU clearance remained constant. Also, the elimination rate constant (k) for salicylate was not significantly affected. 5. Therapeutic response to salicylate therapy was not significantly affected by the decline in SA concentrations.

Rapid high-performance liquid chromatographic assay for the simultaneous analysis of non-steroidal anti-inflammatory drugs in plasma.

A high-performance liquid chromatographic assay has been developed for the determination of a number of non-steroidal anti-inflammatory drugs in plasma. The samples were prepared by adding acetonitrile and perchloric acid to 200 microliter of plasma. Diclofenac, fenoprofen, ketoprofen, naproxen, phenylbutazone, piroxicam and sulindac were quantified in the supernatant produced using a mobile phase of phosphoric acid 0.03% (pH 2.5)-acetonitrile and a detecting wavelength of 254 nm. The reproducibility, linearity, precision and specificity of the assay were determined and found to be satisfactory. Alteration of the detection wavelength to 229 nm also permitted accurate determination of ibuprofen concentration in plasma. While reduction of the organic solvent content of the mobile phase and alteration of wavelength to 313 nm produced a system capable of quantifying salicylate and its metabolites in plasma and by further reducing the detecting wavelength to 237 nm, aspirin also was quantifiable. These methods have been applied in a cross-sectional study of medication compliance among rheumatoid arthritis patients treated with non-steroidal anti-inflammatory drugs.

Functional capacity and treatment data from a community based study of patients with rheumatoid arthritis.

A community based study of rheumatoid arthritis was undertaken to determine patient characteristics and the patterns of treatment. Three hundred and eighty subjects were visited in their homes throughout Tasmania (pop. 430 000) by a research team. The median age of the sample was 60 years (interquartile range (IR) 49-69), with a female predominance of 2.65 to 1. The average onset age was 41 years (IR 30-53). Prescribing data indicated that polypharmacy was not common in the community, and that the use of slow acting antirheumatic drugs (SAARDs) and oral corticosteroids was not widespread. At the time of the study 26% of subjects were assayed fully functional--class I of the American Rheumatism Association's (ARA) functional classifications. The functional capacity data provided evidence that the spectrum of rheumatoid arthritis found in the community differed from that found in specialist rheumatology clinics.

Determinants of compliance in rheumatoid arthritic patients assessed in their home environment.

Patient compliance with prescriber's medication instructions was investigated in 178 rheumatoid arthritis patients treated in community practice. The compliance rate in the sample subjects was estimated to be 63.5%. Disease activity, measured objectively with erythrocyte sedimentation rate (ESR) and subjectively by duration of morning stiffness, was a major incentive for adherence to the treatment regimen. Among subjects with active disease (ESR greater than 20 mm in 1 h), the rate of compliance was 73.8%, but this fell to 52.7% among those with a normal ESR (i.e. ESR less than or equal to 20 mm in 1 h). The motivations and perceptions of the subjects concerning their drug therapy also affected compliance. Compliance was however less dependent on perceptions when active inflammation was present.

Cross-sectional study of rheumatoid arthritis treatment in a university hospital.

Drug prescribing patterns for the management of inpatients and outpatients with rheumatoid arthritis (RA) were investigated. The population of patients resembled published epidemiological descriptions of RA patients with respect to age and sex distribution. Multiple drug therapy was common in the treatment of both hospitalised and clinic patients. 90% of all patients with RA received non-steroidal anti-inflammatory drug (NSAID) therapy, indomethacin and naproxen being the two most frequently prescribed NSAIDs for both in- and outpatients. The vast majority of inpatients (85%) and outpatients (79%) received slow-acting antirheumatic drug (SAARD) treatment. 13% of hospitalised patients received H2-antagonist drugs in addition to their NSAIDs. A high proportion of inpatients (46%) received oral corticosteroids in the management of their rheumatoid arthritis, while only 15% of clinic patients were prescribed corticosteroids.

Community Surveillance Study--perceived response of rheumatoid arthritis patients to NSAIDs.

The perceived effectiveness of nonsteroidal anti-inflammatory drugs was studied in a community population (n=380). The population characteristics of a sample were similar to previous studies. Most patients were on a single NSAID. Rheumatoid arthritis (RA) was found to have a significant impact in terms of disability and lifestyle. Active inflammation was the main incentive to comply with therapy. However, the patients perceptions about the efficacy of the medication, their attitude towards the medication and their motivations for taking it, also affected compliance. A decreased effectiveness of therapy may also be due in part to tolerance to some medications and some evidence of the induction of salicylate metabolism has been reported. Considerable variation in the patients' perception of other forms of therapy for RA were also observed.

An audit of therapeutic drug monitoring procedures--use of theophylline assay services.

Monitoring therapy involving drugs exhibiting high intersubject variation and/or narrow therapeutic index has become more generally accepted in hospitals. This paper describes an audit conducted jointly by clinical pharmacists and clinical biochemists into the use and therapeutic value of a drug monitoring service in a general hospital using theophylline as a model. Assay values were categorized as 'subtherapeutic', 'therapeutic' or 'potentially toxic'. The reporting procedures involving the two departments were evaluated along with action taken by the requesting clinicians. The study showed that 60% of the theophylline assay results fell within the therapeutic range at the time of sampling. However only 38% of samples were considered to have been taken under steady state conditions. There was a significant delay in relaying the results to the clinicians. Procedural changes involving sampling times, analytical techniques, recording and conveying results to clinicians and co-operative policies between the departments of pharmacy and clinical chemistry have been implemented as a result of this study.

Record-linked audit of drug utilization data in a hospital: antimicrobial use on a urology ward.

Antimicrobial drug utilization patterns were studied on a urology ward with a view to establishing base-line data and subsequently determining drug usage data during the implementation of antimicrobial prescribing guidelines. Methods of data collection, storage and interpretation are described. The results of therapeutic audit of the use of antimicrobial agents over a period of time during which discussion, constitution and acceptance of guidelines took place, are described. The effectiveness of a multidisciplinary approach in rationalizing drug prescribing and the effects of intensive monitoring on prescribing patterns are illustrated.

Trimethoprim: clinical use and pharmacokinetics.

The recent marketing of trimethoprim (TMP) as a single drug has resulted in interest in the use of this drug to treat common infections. The history and antibacterial properties of TMP are reviewed. Indications for the clinical use of TMP are presented, and possible new uses for the drug are considered. The significance of adverse effects is discussed. The pharmacokinetic properties of TMP are reviewed with particular emphasis on the renal handling of the drug and its advantages over TMP/sulfonamide combinations in relation to renal function and toxicity.

Recent developments in the treatment of acute urinary tract infections.

A review of the recent literature on acute urinary tract infections reveals some unresolved problems and considerable discussion and reappraisal of the current diagnostic and therapeutic methods. In this review, the rationale for the diagnostic confirmation of the presence, extent and site of infection is presented. Recent developments in the treatment of acute urinary tract infections are discussed. Factors affecting the choice of drug and recent studies concerning the duration of therapy are detained. Studies concerning the treatment of urinary tract infections with trimethoprim alone are reviewed and results of the treatment of acute urinary tract infection with a single dose of trimethoprim at St Radboud Hospital are presented.

Renal excretion of sulphamethoxazole and its metabolite N4-acetylsulphamethoxazole in patients with impaired kidney function.

Plasma and urine concentrations of creatinine, sulphamethoxazole and its metabolite N4-acetylsulphamethoxazole were measured in patients with varying degrees of kidney impairment. The plasma elimination half-life of sulphamethoxazole is not influenced by the kidney function, while the half-life of the metabolite is fully dependent on the kidney function. The renal clearances of the metabolites and that of the parent compound under alkaline urine conditions are linearly related to the creatinine clearance. Kidney impairment affects only the renal clearance of the metabolite, whereas sulphamethoxazole is metabolized (acetylated) independently of kidney function.

Pharmacokinetics and mechanism of renal excretion of short acting sulphonamides and N4-acetylsulphonamide derivatives in man. Structural requirements of sulphonamides for active tubular secretion.

The pharmacokinetics of short acting sulphonamides and a series of N4-acetylsulphonamide derivatives has been investigated. Sulphonamides with a sulphur atom two atomic bond distances from the N1 atom are excreted by active tubular secretion, e.g. sulphamethizole, sulphaethidole and sulphathiasole. When the sulphur atom is replaced by an oxygen or nitrogen atom, active renal excretion no longer occurs. N4-acetylsulphonamides are excreted by active tubular secretion. The renal clearance values of the N4-acetylsulphonamides are not influenced by the substituent at the N1 position. Two groups of N4-acetylsulphonamides can be distinguished. One has a T1/2 of 4-6 h and a renal clearance value of 20-60 ml/min and the second has a T1/2 of 10-20 h and a renal clearance of less than 10 ml/min. N4-acetylsulphonamides are deacetylated to the extent of about 5%.