Antibiotic resistance--what can we do?
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Biomedical subjects
Publications and source records attributed to M Malek.
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BACKGROUND: Few outcome studies directly compare Helicobacter pylori eradication therapy with maintenance H2-antagonist therapy in duodenal ulcer disease. AIM: To examine prospectively the efficacy of H. pylori eradication therapy with ranitidine maintenance therapy over 1 year in patients with confirmed chronic duodenal ulcer. METHODS: One hundred and nineteen patients with active H. pylori infection were randomized to receive ranitidine, 150 mg/day initially (58 patients), or omeprazole, 40 mg/day, amoxycillin 2 g/day and metronidazole 1.2 g/day for 14 days, or omeprazole 40 mg/day and clarithromycin 1.5 g/day, for 14 days (if penicillin-allergic). Symptoms were assessed using the Gastrointestinal System Rating Scale (GSRS) and SF36 quality of life index. RESULTS: 13C urea breath testing confirmed overall treatment success in 100% of patients (58/58) per protocol and 95.1% (58/61) on an intention-to-treat basis. At 4 and 12 months there were no differences in any GSRS symptoms between treatment groups. SF36 analysis showed a perceived health improvement at 4 and 12 months in patients who received H. pylori eradication. However, despite successful H. pylori eradication, one-fifth of patients still required antisecretory therapy. CONCLUSION: Following successful H. pylori eradication, chronic duodenal ulcer patients were at least as well symptomatically as when taking maintenance ranitidine. They perceived that their health had improved, but a subgroup was still acid-suppression dependent.
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This study compares 100 mg daily fluconazole with oral polyenes four times daily in the prophylaxis of fungal infections in immunocompromised patients, to determine a cost-minimization strategy. Data was gathered through a literature survey and clinical interviews conducted in nine different UK hospitals. This was used to construct a decision tree, modelling the drug choices available to a clinician at various stages of a patient's treatment, and assigning probabilities to the different corresponding outcomes. UK cost data were fed into this model to determine the expected cost per patient of the different prophylaxis strategies. Two different patient groups were considered: chemotherapy-only patients, and bone-marrow-transplant (BMT) patients who have higher risks of fungal infection. Probabilities derived from the literature suggest that a cost-minimization strategy to manage both chemotherapy patients and BMT patients is to administer oral fluconazole, both as prophylaxis and as first line treatment, against superficial fungal infection. Probabilities gathered from clinical interviews yield similar results, suggesting that the cost-minimization strategy with chemotherapy-only patients is to administer oral polyenes as prophylaxis, and oral fluconazole in case of superficial fungal infection, while for BMT patients it is a combination of fluconazole and oral polyenes as prophylaxis, with oral fluconazole for the treatment of superficial fungal infections. Using the probabilities from the literature, the lowest cost strategies produce an expected cost of pounds 567.20 for chemotherapy-only patients, and an expected cost of pounds 804.87 for BMT patients for a course of treatment lasting from seven to 28 days. The clinical interview probabilities produce expected costs of pounds 826.48 and pounds 1529.43, respectively. Sensitivity analysis was then conducted, and it was found that in the majority of cases, using the literature probabilities, the cost-minimizing strategy remained prophylaxis with oral fluconazole. The sensitivity analysis for chemotherapy-only patients using the interview probabilities tended to favour oral polyenes as the cost-minimization strategy, whereas for BMT patients the sensitivity analysis favoured a combination of fluconazole and oral polyenes in the majority of cases. The key economic advantage of prophylaxis with fluconazole or a combination of fluconazole with oral polyenes in the prophylaxis of fungal infection in immunocompromised patients, results from the reduction of the expected cost of subsequent fungal infection among those who are most at risk.
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.
Anti-infective drugs account for between 3 and 25% of all prescriptions, between 6 and 21% of the total market value of drugs in a single country, and up to 50% of the drug budget in hospitals. Not surprisingly, in an era when cost-containment policies are at the top of the agenda, issues related to pharmaco-economics of antibacterial treatment have assumed an important part in these policies. However, there are still some misunderstandings regarding the precise terminology and difference in methodology of pharmacoeconomics. The aim of this paper is to explain the genealogy of pharmacoeconomics and various methods currently used in the application of this young discipline to anti-infective treatment.
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In patients with duodenal ulcer, omeprazole plus clarithromycin (OC) has achieved Helicobacter pylori eradication rates of about 80%, compared with 50% for omeprazole plus amoxicillin (OA). The drug acquisition costs for OC are 102.92 pounds sterling (pounds) compared with 38.96 pounds for OA using generic amoxicillin and 51.63 pounds using the proprietary brand 'Amoxil' (costs for 2-week regimens in 1995). The aim of this analysis was to estimate the total healthcare costs to the general practitioner (GP) of eradication therapy using a simple generalised model. Data about current practice in the UK were obtained from 502 respondents in a survey of hospital specialists and GPs. It was assumed that patients would derive no benefit from eradication therapy unless they had a duodenal ulcer, and that all OA patients received generic amoxicillin. The survey confirmed that OA was the commonest eradication therapy prescribed by UK GPs at that time. Three distinct patient groups were identified: patients with proven duodenal ulcer who were already receiving maintenance treatment with a histamine H2 receptor antagonist, and new patients with dyspepsia who were subdivided into those aged above or below 45 years. Patients receiving maintenance treatment for a duodenal ulcer would be prescribed eradication therapy by their GP without further endoscopy. If dyspepsia recurred after eradication therapy, they would be referred to a gastroenterologist, who would perform an endoscopy to confirm the recurrence of ulceration. In this model, the expected total healthcare costs (i.e. the costs of drug acquisition and subsequent treatment when required) following prescription of eradication therapy were lower for OC (157 pounds) than for OA (173 pounds). New patients aged over 45 years would be referred for endoscopy because of the risk that dyspepsia might be the initial presentation of gastric cancer. If duodenal ulceration was found, eradication therapy would be prescribed and, if dyspepsia remained or recurred, the patient would be referred back to the gastroenterologist. In this case, it was considered unlikely that a further endoscopy would be performed. Thus, the healthcare costs associated with failure of eradication in these patients were less than for patients on maintenance treatment, and the expected total healthcare costs were higher for OC (349 pounds) than for OA (335 pounds). Finally, a new patient aged under 45 years with dyspepsia would have eradication therapy prescribed on the basis of a clinical diagnosis of duodenal ulcer plus serological evidence of infection with H. pylori. Continuation or recurrence of dyspepsia would result in referral to a gastroenterologist, who would perform an endoscopy. The total expected healthcare costs were higher for OC (253 pounds) than for OA (251 pounds). The cost effectiveness of OA was sensitive to changes in the default costs (i.e. the average costs from the survey used in the decision analysis), particularly in patients < 45 years old. In these patients, OC would become the cheaper option if amoxicillin were prescribed by brand name instead of in generic form. In this patient group, the outcome was crucially dependent on the accuracy of the clinical diagnosis of duodenal ulcer; if this was at least 60%, then OC would be the cheaper regimen. Overall, the model clearly shows that the higher drug cost of OC is likely to be substantially offset by savings in other healthcare costs. If the direct healthcare costs of OC are higher than OA, then the decision maker must consider the indirect and intangible costs associated with failure of eradication therapy.
The pharmaceutical industry offers the world's population alleviation and cure from a variety of medical conditions, while also contributing to the economic performance of many countries. The potential importance of these characteristics have made the industry an area of intense debate, criticism and praise. This review aims to clarify some of the arguments surrounding the industry on both sides of the fence, and by doing so, to provide a balanced introduction on which opinions may be made.
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.
The importance of definition and post-discharge wound surveillance on reported wound infection rates have been studied, using data taken from a prospective, randomized, placebo-controlled, double-blind trial of the effect of whole body disinfection on postoperative wound infection rates. All patients admitted for an elective clean or potentially contaminated surgical procedure over a 32-month period were recruited into the study. Of the 3733 patients recruited, 3466 completed the study. Wound infection (which is defined for this study) is the main outcome that was examined. The effect of careful post-discharge follow-up of patients to look for wound infections was analysed for age, wound type and presence or absence of a drain. Sixty percent of postoperative wound infections occurred after discharge. A rising wound infection rate with increasing age was observed in the in-hospital cohort whereas the incidence of outpatient wound infections declined with age. This finding is attributed to the longer in-hospital stay encountered in patients above 50 years old (median, 3 vs. 5 days, P < 0.00001). Although clean operations had a significantly lower in-hospital infection rate, potentially contaminated procedures had a lower outpatient infection rate. A similar picture was observed in other subgroups of operations including horizontal versus vertical wounds and use of drains. When assessing reported wound infection rates, the definition of wound infection used and the extent of follow-up must be known to enable accurate assessment of the results.
People are more vulnerable to infection at the extremes of age for a variety of reasons, the most important being that they are more likely to be in hospital in a crowded ward environment and to be at risk from hospital acquired infection. Recognition of this increased vulnerability to infection should be accompanied by equal emphasis on their increased susceptibility to nosocomial disease arising from the diagnosis or treatment of infection. An economic evaluation of infection at the extremes of age should include an assessment of need made in terms of the capacity of patients to benefit from investigation or treatment. Benefits should not be confused with treatment effects such as reduction in pyrexia or correction of other physiological abnormalities. Ideally benefits should be quantified in a manner which allows comparison with the cost-effectiveness of other uses of health care resources. In order to achieve this aim clinicians must understand the economic terms opportunity cost and marginal cost-effectiveness. These terms are defined in general terms and then applied to examples of investigation, prevention and treatment of infection at the extremes of age.
Economic analysis is founded on the assumption that resources are limited and that they should be used in a way that maximises the benefits gained. It should be clear that economic analysis must be based on a consideration of choices for resource utilisation. Pharmacoeconomics extends these assumptions to drug treatment. Therefore, a full pharmacoeconomic analysis must consider two or more alternative treatments and should be founded on measurement of incremental cost, incremental efficacy, and the value of successful outcome. Most doctors would agree that it is easy to choose between two treatments if the least expensive drug is also the most effective. Economic analysis is required whenever the more expensive of two options is also the more effective. In this instance, the decision maker must believe that the value of one additional successful outcome is greater than the investment made in the more effective treatment. This approach would be a suitable model for comparing new oral third generation cephalosporins with cheaper oral drugs such as amoxicillin. Another decision requiring economic analysis is the choice between a new, oral third generation cephalosporin and an older intravenous formulation of a third generation cephalosporin. In this case, the new treatment is cheaper than the old treatment and the decision maker must be convinced that the oral treatment is as effective as the intravenous treatment. Statistically, it is only possible to exclude a difference of a given magnitude.(ABSTRACT TRUNCATED AT 250 WORDS)
The growth of expenditures on healthcare and pharmaceutical products is a concern to third-party payers because of the absence of market discipline (price signals that consumers face). Cost-effectiveness analysis is a method that allows third-party payers to systematically make judgements about the 'value for money' of these products. It moves beyond simple unit price comparisons of alternate interventions/products to consider the full stream of relevant cost and benefits. As formulary committees begin to adopt the systematic use of cost-effectiveness analyses to inform the debate, the exercise will move from an academic to a more practical application. This transition will require several important changes including defining the purpose of cost-effectiveness analysis, measurement of outcomes and data, format of reports, and contractual arrangements between the pharmaceutical industry and analysts. As more 'real world' experience is gained in the practical application of cost-effectiveness analysis, the quality of data will improve as will its value as an aid to decision making.
BACKGROUND: Several new antibacterial drugs have been introduced in the last 10 years with the aim of improved treatment of respiratory tract infection. AIM: The study set out to use repeat consultations as a measure of the outcome of antibiotic treatment for respiratory tract infection, and to develop a simple model for discussion of the cost effectiveness of alternative antibiotic treatments. METHOD: All consultations to one practice during a single winter were reviewed by one general practitioner. RESULTS: A total of 1140 patients had acute symptoms suggestive of respiratory infection. Of these, 899 patients (79%) were prescribed antibiotics at the first consultation and 160 of the 899 patients (18%) returned for one or more repeat consultations; only nine repeat consultations were due to adverse effects of the antibiotics prescribed. Only two patients were admitted to hospital for respiratory symptoms following initial antibiotic therapy and both patients had additional reasons for their admission. Using the highest estimates, the cost of a repeat consultation was found to be 28.54 pounds. These data were used to calculate how much more might be spent on more effective antibiotics at the first consultation. It would be difficult to justify increasing the cost of antibiotic treatment by more than 5 pounds per patient, even if the new treatment were 100% effective and all repeat consultations were due to treatment failure (5 pounds is equal to 28.54 pounds x 0.18, which is the maximum cost of a repeat consultation multiplied by the proportion of patients prescribed antibiotics who make repeat consultations). CONCLUSION: From these results and a review of the literature it can be concluded that new antibacterial drugs will have to be carefully targeted if they are to prove cost effective in practice. Other methods for reducing repeat consultation merit investigation.
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Diaphragmatic stimulation as a complication of cardiac pacing due to right ventricular perforation of an endocardial lead or penetration of a screw-in lead along the right atrial free wall, adjacent to the right phrenic nerve, has previously been described. A case of diaphragmatic pacing due to inadvertent insertion of a temporary pacing lead into the left pericardiophrenic vein via the left internal jugular vein is presented and anatomical considerations are discussed.
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