Rapid identification and antimicrobial susceptibility testing reduce antibiotic use and accelerate pathogen-directed antibiotic use.

INTRODUCTION: Rapid bacterial identification and susceptibility tests can lead to earlier microbiological diagnosis and pathogen-directed, appropriate therapy. We studied whether accelerated diagnostics affected antibiotic use and patient outcomes. PATIENTS AND METHODS: A prospective randomized clinical trial was performed over a 2-year period. Inpatients were selected on the basis of a positive culture from normally sterile body fluids and randomly assigned to either a rapid intervention arm or the control arm. The intervention arm used the Vitek 2 automated identification and susceptibility testing device, combined with direct inoculation of blood cultures. In the control arm, the Vitek 1 system inoculated from subcultures was used. Follow-up was 4 weeks after randomization. RESULTS: A total of 1498 patients were randomized: 746 in the intervention arm and 752 in the control arm. For susceptibility testing, the rapid arm was 22 h faster than the control arm, and for identification, it was 13 h faster (P < 0.0001). In the rapid arm, antibiotic use was 6 defined daily doses lower per patient than in the control arm (P = 0.012). Whereas antibiotics were switched more in the rapid group on the day of randomization (P = 0.006), in the control group they were switched more on day two (P = 0.02). Mortality rates did not differ significantly between the two groups (17.6% versus 15.2%). CONCLUSIONS: While rapid bacterial identification and susceptibility testing led to earlier changes and a significant reduction in antibiotic use, they did not reduce mortality.

Immunotherapy with autologous tumor cell-BCG vaccine in patients with colon cancer: a prospective study of medical and economic benefits.

We have completed a multicenter, randomized controlled phase III clinical trial in Stages II and III colon cancer patients with active specific immunotherapy (ASI) using autologous tumor cells with an immunomodulating adjuvant bacillus Callmette-Guerin (BCG) vaccine (OncoVAX) in an adjuvant setting. In this study, patients were randomized to receive either OncoVAX therapy or no therapy after surgical resection of the primary tumor and stratified by stage of disease. Since the biologic essence of the effective tumor immunotherapy is the presence in the vaccine of a minimum number of viable, metabolically active, autologous tumor cells, the processing of the vaccine product, occurred within 48 h after surgery. Analysis of prognostic benefit in the pivotal phase III trial, with a 5.8 year median follow-up, showed that a beneficial effect of OncoVAX is statistically significant for all endpoints including recurrence-free interval, overall survival, and recurrence-free survival in Stage II colon cancer patients. Surgery alone cures approximately 65% of Stage II (Dukes B2, B3) colon cancer patients. In the remaining patients, OncoVAX in an adjuvant setting, significantly prolongs recurrence-free interval (57.1% relative risk reduction) and significantly improves 5-year overall survival and recurrence-free survival. No statistically significant prognostic benefits were achieved in Stage III (Duke's C1-C3) patients. A health economics assessment was performed on these results in Stage II colon cancer patients using disease-free survival and overall survival (for the entire intent-to-treat population). Cost-effectiveness, cost-utility and sensitivity analysis were applied with, cost of life years, recurrence-free life years and quality adjusted life years (QALYs) as the primary endpoints to this analysis. The perspective of the economic analysis was the current direct medical cost established by the health care providers. The introduction of new technologies often leads to additional costs. This report verified that the use of OncoVAX for patients with Stage II colon cancer not only has significant prognostic benefit and positive clinical outcomes, but also showed that OncoVAX therapy yields impressive health economics benefits.

The cost of atopic dermatitis in the Netherlands: an international comparison.

BACKGROUND: Only a few international studies have assessed the economic burden of atopic dermatitis (AD), and no costs-of-illness study for AD has been done for the Netherlands. OBJECTIVES: To estimate the incidence, prevalence and health-care costs of AD in the Netherlands and to put these in an international perspective. METHODS: We conducted a retrospective cohort study by using the data of an information system of general practitioners (GPs). To calculate the health-care costs at the primary care level we assessed medical resources utilization. We assessed the costs of patients with more severe AD from a retrospective study of patient files at the department of dermatology of a general hospital. We compared our results with costs-of-illness studies for other countries. RESULTS: The overall general population incidence and prevalence of AD were 0.8% and 2.3%, respectively. The incidence and prevalence were high among children until the age of 6 years, respectively, 3.1% and 11.3%, but decreased rapidly thereafter. The total mean health-care costs per patient were USD71. The most significant costs were due to visits to the GP (USD32) and medication, mostly corticosteroids (USD21). Young children were treated more often with emollients alone. Only 7.8% of patients were referred to a specialist. The mean costs for these patients were USD186. Costs-of-illness studies for Australia, Germany, the U.K., the U.S.A. and the Netherlands suggested that the costs associated with AD vary considerably across countries. Estimates of the costs-of-illness for AD ranged from USD71 in the Netherlands to USD2559 in Germany per patient due to variation in the study population (GP vs. hospital) and the number of cost components included. Studies that included costs due to the time spent on treatment had relatively high estimates. CONCLUSIONS: The prevalence and incidence of AD are high among young children. In general, the health-care costs for AD were low. Patients' out-of-pocket costs were relatively high.

Practice, efficacy and cost of staging suspected non-small cell lung cancer: a retrospective study in two Dutch hospitals.

BACKGROUND: A study was undertaken to investigate the clinical practice, yield, and costs of preoperative staging in patients with suspected NSCLC and to obtain baseline data for prospective studies on the cost effectiveness of (18)F-fluorodeoxyglucose positron emission tomography in the management of these patients. METHODS: A retrospective study of the medical records of all patients with suspected NSCLC was performed during a 2 year interval (1993-4) in an academic and a large community hospital. RESULTS: Three hundred and ninety five patients with suspected NSCLC were identified; 58 were deemed to be medically inoperable and 337 patients proceeded to the staging process. Staging required a mean (SD) of 5.1 (1.5) diagnostic tests per patient (excluding thoracotomy) carried out over a median period of 20 days (IQR 10-31). Many of the tests (including both invasive and non-invasive) were done because previous imaging tests had suggested metastases, and in most cases the results of initial tests proved to be false positives. After clinical staging, 168 patients were considered to be resectable (stage I/II) and 144 patients underwent surgery with curative intent. At surgery 33 patients (23% of those who underwent surgery) were found to have irresectable lesions and 19 (13%) had a benign lesion. Surgery was also considered to be futile in 22 patients (15%) who developed metastases or local recurrence within 12 months following radical surgery. Hospital admission was responsible for most of the costs. CONCLUSION: In many patients staging involved considerable effort in terms of the number of diagnostic tests, the duration of the staging period and the cost, with limited success in preventing futile surgery. Failures relate to the quality of diagnostic preparation at every level of the TNM staging system.

The cost effectiveness of tapered versus abrupt discontinuation of oral cyclosporin microemulsion for the treatment of psoriasis.

OBJECTIVE: To assess the cost effectiveness of tapered versus abrupt discontinuation of a microemulsion formulation of cyclosporin in patients with chronic plaque psoriasis. METHODS: A cost-effectiveness analysis was performed in parallel with a non-blind, multicentre, international clinical trial of the safety and efficacy of intermittent short courses of cyclosporin. Direct and indirect costs were considered within a 1-year period following randomisation. PATIENTS: Patients with chronic plaque psoriasis inadequately controlled with topical treatment. STUDY PERSPECTIVE: The study was conducted from a societal perspective and was performed using data from Canada, Spain, Turkey and the UK. MAIN OUTCOMES MEASURES: The health outcome used was the total number of systemic therapy-free days (STFDs) over the first year. The mean incremental cost-effectiveness ratio (ICER) was determined by dividing the differences in average cost per patient by the differences in average STFDs per patient. RESULTS: The overall ICER was dominant because tapered discontinuation was associated with both lower costs and improved efficacy in comparison with abrupt discontinuation. Further analyses showed that tapered discontinuation was a cost-effective alternative to abrupt discontinuation therapy, even when a conservative definition for cost effectiveness was adopted. CONCLUSION: This cost-effectiveness analysis demonstrated that tapering cyclosporin was more cost effective than abruptly stopping cyclosporin in patients with chronic plaque psoriasis.

Quality of life and clinical outcome in psoriasis patients using intermittent cyclosporin.

BACKGROUND: Psoriasis causes considerable patient morbidity and can seriously affect a patient's quality of life (QoL). OBJECTIVES: To investigate the relationships between changes in QoL and measures of severity and extent of disease, and itch, in patients with chronic plaque psoriasis receiving intermittent short courses of cyclosporin (Neoral). METHODS: This study was performed as part of an international trial investigating the safety, efficacy and total costs of intermittent short courses of cyclosporin (the PISCES study). All patients received cyclosporin until clearance and were then followed up until relapse. On relapsing, patients received another course. Patients were followed up for a minimum of 1 year during which they could receive as many courses of treatment as necessary. In a subgroup (n = 255) of patients in the trial, the Dermatology Life Quality Index (DLQI) was used to assess the impact of psoriasis and its treatment on the patients' health status at the beginning and end of each treatment period. At the beginning and end of each treatment period, as well as at 2-weekly visits, the extent and severity of disease, together calculated into a modified Psoriasis Area and Severity Index (PASI), and itch were recorded. Data were analysed using the Wilcoxon matched pairs test, multivariate Hotelling's T2 tests, and Spearman's rank correlation coefficients (rs). RESULTS: During treatment, a clear impact on the overall DLQI scores and in the scores in all six DLQI headings was found (i.e. an improvement in QoL; P < 0.001 in all scores). Also, significant decreases in PASI and itch scores were found (P < 0.001). Multivariate analyses confirmed that a decrease in PASI and itch scores was accompanied by an impact on the DLQI scores during and between the two treatment periods (P < 0.0001). Statistically significant but weak correlations were found between changes in QoL and changes in PASI (rs = 0.40 and 0.24 for the first and second treatment periods, respectively) and itch scores (rs = 0.31 and 0.42, respectively). CONCLUSIONS: Intermittent short courses of cyclosporin clearly improve the QoL of the patients and decrease the extent and severity of disease and itch. Changes in clinical outcome scores are accompanied by changes in QoL. The weak correlations between changes in QoL and clinical measures may suggest that no clear relationship between QoL and clinical outcomes exists. However, due to the inclusion and exclusion criteria of the study, both QoL and clinical outcome measures do not show much variation among this homogeneous group of patients. As long as the relationship between clinical outcome parameters and measures of QoL is not completely clear, both measures of health should be considered in adequate, patient-orientated clinical decision making.

Toward less futile surgery in non-small cell lung cancer? A randomized clinical trial to evaluate the cost-effectiveness of positron emission tomography.

Non-small cell lung cancer can be cured if the patient is medically operable and the tumor resectable. Current diagnostic strategies are aimed to detect tumor deposits that preclude resection with curative intent. However, these strategies are rather inefficient, resulting in a large number of futile invasive procedures. In the early 1990s positron emission tomography (PET) showed promising results at its introduction in the clinic, especially in oncology. A large number of accuracy studies have reported that PET is superior to conventional imaging. However, whether PET ultimately improves patient outcome should ideally be assessed by means of a randomized controlled trial. No such design has been applied to evaluate PET in oncology so far. The PLUS study was designed to compare the current strategy of conventional methods with a strategy where PET was added after completion of noninvasive techniques. Patients considered operable by the physician at this point were then randomly assigned to PET and further consequences or to standard procedures of mediastinoscopy or thoracotomy. Primary outcome events were futile thoracotomies. The trial randomized 188 patients from nine hospitals in 1 year. Patient enrollment has been stopped and data collection is in progress. The results will be published in 2001. Control Clin Trials 2001;22:89-98