To evaluate the costs, consequences, effectiveness, and safety of ciprofloxacin vs standard antibiotic care in patients with an initial acute exacerbation of chronic bronchitis (AECB) as well as recurrent AECBs over a 1-year period.
A total of 240 patients, 18 years or older with chronic bronchitis, with a history of frequent exacerbations (three or more in the past year) presenting with a type 1 or 2 AECB (two or more of increased dyspnea, increased sputum volume, or sputum purulence).
The assessment included AECB symptoms, antibiotics prescribed, concomitant medications, adverse events, hospitalizations, emergency department visits, outpatient resources such as diagnostic tests, procedures, and patient and caregiver out-of-pocket expenses. Patients completed the Nottingham Health Profile, St. George's Respiratory Questionnaire, and the Health Utilities Index. The parameters were recorded with each AECB and at regular quarterly intervals for 1 year. These variables were compared between the ciprofloxacin-treated group and the usual-care-treated group.
Patients receiving ciprofloxacin experienced a median of two AECBs per patient compared to a median of three AECBs per patient receiving usual care. The mean annualized total number of AECB-symptom days was 42.9+/-2.8 in the ciprofloxacin arm compared to 45.6+/-3.0 days in the usual-care arm (p=0.50). The overall duration of the average AECB was 15.2+/-0.6 days for the ciprofloxacin arm compared to 16.3+/-0.6 days for the usual-care arm. Treatment with ciprofloxacin tended to accelerate the resolution of all AECBs compared to usual care (relative risk=1.20; 95% confidence interval [CI], 0.91 to 1.58; p=0.19). Treatment assignment did not affect the interexacerbation period but a history of severe bronchitis, prolonged chronic bronchitis, and an increased number of AECBs in the past year were associated with shorter exacerbations-free periods. There was a slight, but not statistically significant, improvement in all quality of life measures with ciprofloxacin over usual care. The only factors predictive of hospitalization were duration of chronic bronchitis (odds ratio=4.6; 95% CI, 1.6, 13.0) and severity of chronic bronchitis (odds ratio=4.3; 95% CI, 0.8, 24.6). The incremental cost difference of $578 Canadian in favor of usual care was not significant (95% CI, -$778, $1,932). The cost for the ciprofloxacin arm over the usual care arm was $18,588 Canadian per quality-adjusted life year gained. When the simple base case analysis was expanded to examine the effect of risk stratification, the presence of moderate or severe bronchitis and at least four AECBs in the previous year changed the economic and clinical analysis to one favorable to ciprofloxacin with the ciprofloxacin-treated group having a better clinical outcome at lower cost ("win-win" scenario).
Treatment with ciprofloxacin tended to accelerate the resolution of all AECBs compared to usual care; however, the difference was not statistically significant. Further, usual care was found to be more reflective of best available care rather than usual first-line agents such as amoxicillin, tetracycline, or trimethoprim-sulfamethoxazole as originally expected. Despite the similar antimicrobial activities and broad-spectrum coverage of both ciprofloxacin and usual care, the trends in clinical outcomes and all quality of life measurements favor ciprofloxacin. In patients suffering from an AECB with a history of moderate to severe chronic bronchitis and at least four AECBs in the previous year, ciprofloxacin treatment offered substantial clinical and economic benefits. In these patients, ciprofloxacin may be the preferred first antimicrobial choice.
Because of the potential for large variability among countries in the utilization and cost of health care resources, it is important to assess the appropriateness of combining economic data across the countries in a multinational clinical economic trial. We show how available tests for interaction can be applied to economic endpoints, including cost-effectiveness ratios and net health benefits. This analysis includes a characterization of possible interactions being quantitative or qualitative in nature. In the absence of interaction, a pooled estimate of the economic endpoint should be representative of the participating countries. We explore the analytic issues by further analysing data from the Scandinavian Simvastatin Survival Study (4S).
To survey medical practitioners' experience with and attitudes toward litigation alleging medical malpractice.
A survey using a questionnaire.
The Sudbury and Manitoulin Health District of Northern Ontario.
Medical practitioners in the area.
Physicians are sometimes negligent; malpractice is not simply created by entrepreneurial lawyers and patients with unrealistic expectations. At present malpractice is restrained by both the threat of civil litigation and the disciplinary committee of the Ontario College of Physicians and Surgeons.
We must address the fear of malpractice suits if the North is to attract and retain the physicians it needs to provide modern standards of medical care.
Cites: Am J Psychiatry. 1984 Apr;141(4):563-56703136
Cites: CMAJ. 1989 Sep 1;141(5):434-72766184
Cites: Am J Psychiatry. 1985 Apr;142(4):437-403976916
Cites: Can Med Assoc J. 1984 Sep 15;131(6):645-6, 648-506478351
BACKGROUND: Despite the growing use of statins, many hypercholesterolaemic patients fail to reach their lipid goal and remain at elevated risk of coronary heart disease (CHD). Alternative treatment strategies, such as ezetimibe coadministration and statin titration, can help patients achieve greater lipid control, and thereby lower their CHD risk. But is it cost effective to more aggressively lower cholesterol levels across a broad range of current statin users? METHODS: Using a decision-analytic model based on epidemiological and clinical trials data, we project the lifetime benefit and cost of alternative lipid-lowering treatment strategies for CHD and non-CHD diabetic patients in Germany, Spain and Norway. RESULTS: It is projected that from 40% to 76% of these patients who have failed to reach their lipid goal with their current statin treatment will be able to reach their goal with ezetimibe coadministration; this represents a gain of up to an additional absolute 14% who will be able to reach their goal compared with a 'titrate to goal' strategy where patients are titrated in order to reach their lipid goal (up to the maximum approved dose). For CHD patients, the estimated incremental cost-effectiveness ratio for ezetimibe coadministration is under Euro 18 000 per life-year gained (Euro/LYG) and 26 000 Euro/LYG compared with strategies based on the observed titration rates and the aggressive 'titrate to goal' strategy, respectively; for non-CHD diabetic patients, these ratios are under 26 000 Euro/LYG and 48 000 Euro/LYG for ezetimibe coadministration compared with the two titration strategies. CONCLUSION: Compared with statin titration, ezetimibe coadministration is projected to be cost effective in the populations and countries studied.
AIMS/HYPOTHESIS: The purpose of this study is to investigate the cost-effectiveness of simvastatin in diabetic patients, using prospectively collected outcomes data from the Scandinavian Simvastatin Survival Study. METHODS: Diabetic patients were identified using two different classifications schemes: Clinical history (diabetic, non-diabetic) and the new American Diabetes Association definition (diabetic, impaired fasting glucose, normal fasting glucose). The analysis is based on prospectively collected data from the trial on hospitalization for cardiovascular problems, study drug utilization and mortality. The incremental cost per life year saved with simvastatin is estimated using costs from Sweden (primary) and other European countries. RESULTS: Hospitalizations for cardiovascular problems were considerably reduced with simvastatin therapy, with the greatest differences in the diabetic subgroups. Reductions in hospitalizations in the diabetic group resulted in substantial hospital cost savings that offset 67 to 76 % of the drug cost (depending on the classification used). For the diabetic patients, the estimates of the cost per life-year gained ranged from 1600 Euros (based on clinical history) to 3200 Euros (based on American Diabetes Association) using Swedish costs. In the other evaluated European countries treatment with simvastatin showed a favourable cost-effectiveness ratio independent of differences in local health care unit costs. CONCLUSION/INTERPRETATION: For all subgroups in the diabetic classification schemes, treatment with simvastatin resulted in estimates of cost per life-year gained that were well within the range generally considered to be cost effective. Based on the Scandinavian Simvastatin Survival Study, simvastatin therapy provides good value for money in both diabetic and non-diabetic patients with cardiovascular disease. [Diabetologia (1999) 42: 1293-1301]
The Scandinavian Simvastatin Survival Study showed that simvastatin treatment reduced cardiovascular events in hypercholesterolemic subjects with coronary heart disease. The clinical benefits of therapy were similar in all three subgroups: normal fasting glucose (NFG, n = 3,237), impaired fasting glucose (IFG, n = 678), and diabetes (n = 483). This analysis compared the costs of simvastatin treatment with the costs of cardiovascular disease-related hospitalizations in the three subgroups.
The cost of simvastatin treatment was defined as the average retail price and the cost of drug safety monitoring and adverse experiences. The costs of cardiovascular disease-related hospitalizations were determined by actual rates of hospitalization and 1995 MEDSTAT diagnosis-related group costs.
Within trial, simvastatin treatment cost approximately $6,000 per patient. Simvastatin treatment reduced cardiovascular disease-related hospitalizations by 23% in NFG (P = 0.001), 30% in IFG (P = 0.015), and 40% in diabetic subjects (P = 0.007) within trial (median follow-up of 5.4 years). Average length of stay was reduced by 2.4 days in diabetic subjects (P = 0.021). Total cardiovascular disease-related hospital days were reduced by 28% (P
Twenty-three patients were identified as having either coronary stent embolization or misdeployment at our center over a 4-year period. They were matched to an equal number of controls who underwent a stenting procedure but in whom embolization or misdeployment did not occur. Baseline demographic characteristics were similar between the 2 groups. The embolization group required higher mean predilation pressure than the control group and more of the embolization group required a predilation pressure >10 atm before attempted stent placement (7 vs 1, p = 0.02). Total procedure and fluoroscopy time as well as dye volume were dramatically higher in the embolization group compared with the control group. Lesion angulation >45 degrees was predictive of stent embolization and 6 of 23 (23%) stents embolized during passage through a previously deployed stent. Sixteen cases of stent embolization and/or misdeployment occurred within the coronary circulation, 8 of which were retrieved, and 7 stents embolized to the central and/or peripheral circulation. A total of 23 major adverse coronary events occurred in the case group versus 7 events in the control group (p = 0.04) over a mean follow-up of 36 +/- 13 months. Fifteen of the events (65%) in the case group occurred in those 8 patients in whom the stent remained in the coronary circulation, including 3 bypass surgeries, 2 myocardial infarctions, 5 repeat percutaneous interventions, and 1 death after hospital discharge. Only 1 patient in whom the stent embolized outside the coronary circulation demonstrated possible evidence for peripheral vascular insufficiency. Intracoronary stent embolization in which the stent remains misdeployed in the coronary circulation is associated with poor long-term outcomes. Extracoronary stent embolization is associated with minimal long-term sequelae.
The multiple organ dysfunction score (MODS) describes and quantifies organ-specific physiology. The objective of this study was to examine the relation between six components of MODS (cardiovascular, respiratory, renal, central nervous system, hepatic, and hematologic) measured at admission to the intensive care unit (ICU) and during the ICU stay, with time to death in the ICU.
Prospective observational cohort study.
Sixteen Canadian ICUs.
A total of 1,200 patients were mechanically ventilated for >48 hrs.
The six organ systems comprising MODS were measured at ICU admission (baseline scores) and daily thereafter. The change in organ dysfunction each day (serial scores) were calculated as daily component scores minus the corresponding baseline component scores. In Cox regression analyses, the independent explanatory variables were the MODS components measured at baseline and serially, and the dependent variable was the time from admission to ICU mortality. When each organ system was analyzed individually, both the baseline and serial MODS for the cardiovascular, respiratory, renal, central nervous system, and hematologic components were significantly associated with ICU mortality. After adjusting for the serial hepatic score, the baseline hepatic score was unrelated to mortality. After adjusting for all baseline and serial MODS components in aggregate, four organ systems were significantly associated with ICU mortality: cardiovascular (baseline relative risk [RR], 1.5; serial RR, 1.4); respiratory (baseline RR, 1.4; serial RR, 1.4); renal (baseline RR, 1.3; serial RR, 1.5); and central nervous system (baseline RR, 1.6; serial RR, 1.7). We found that the relative risk of mortality related to organ dysfunction varied significantly over time and among organ systems. Baseline respiratory function was not associated with mortality until the second ICU week (week 1: RR, 1.1 [0.9-1.4]; week 2 onward: RR, 1.9 [1.5-2.4]); the same was true for the change in respiratory function as measured by the serial respiratory score (week 1: RR, 1.2 [1.0-1.5]; week 2 onward: RR, 1.7 [1.4-2.1]). The serial hepatic score was not associated with mortality until the fourth ICU week (weeks 1-3: RR, 0.9 [0.7-1.1]; week 4 onward: RR, 1.4 [1.0-2.0]).
Organ dysfunction scores describe physiology at ICU admission and during ICU stay. Although patterns vary by system, daily MODS component scores provide additional prognostic value over baseline MODS.
Comment In: Crit Care Med. 2001 Nov;29(11):2223-411700430
The question as to whether or not any or all of the phenoxy herbicides are carcinogenic to humans continues to be evaluated. We review the evidence available from the retrospective cohort and case-control epidemiology studies. Graphs of the individual probability densities for the odds ratios from the eight case-control studies of soft-tissue sarcoma, Hodgkin's disease, or non-Hodgkin's lymphoma demonstrate gross inconsistencies which are not likely to be attributable to chance. Early studies, conducted in Sweden, had indicated strong associations, but subsequent work from New Zealand and the United States has failed to substantiate those findings. The reasons for the discordant results may relate more to methodologic problems in the earlier studies than to qualitative or quantitative differences in the exposures of the underlying populations. The retrospective cohort studies offer the advantage of having focused on occupational groups believed to have had the highest exposures, although they have been criticized as being individually too small to assess the risks of the rarer forms of cancer. Consideration of the combined cohort studies of workers exposed to the phenoxy herbicides per se provides little or no evidence of carcinogenicity. Thus, the total weight of evidence currently available does not support a conclusion that the phenoxy herbicides present a carcinogenic hazard to humans.
Natural history models of breast cancer progression provide an opportunity to evaluate and identify optimal screening scenarios. This paper describes a detailed Markov model characterising breast cancer tumour progression.
Breast cancer is modelled by a 13-state continuous-time Markov model. The model differentiates between indolent and aggressive ductal carcinomas in situ tumours, and aggressive tumours of different sizes. We compared such aggressive cancers, that is, which are non-indolent, to those which are non-growing and regressing. Model input parameters and structure were informed by the 1978-1984 Ostergotland county breast screening randomised controlled trial. Overlaid on the natural history model is the effect of screening on diagnosis. Parameters were estimated using Bayesian methods. Markov chain Monte Carlo integration was used to sample the resulting posterior distribution.
The breast cancer incidence rate in the Ostergotland population was 21 (95% CI: 17-25) per 10?000 woman-years. Accounting for length-biased sampling, an estimated 91% (95% CI: 85-97%) of breast cancers were aggressive. Larger tumours, 21-50?mm, had an average sojourn of 6 years (95% CI: 3-16 years), whereas aggressive ductal carcinomas in situ took around half a month (95% CI: 0-1 month) to progress to the invasive =10?mm state.
These tumour progression rate estimates may facilitate future work analysing cost-effectiveness and quality-adjusted life years for various screening strategies.