Prediction of protein subcellular locations using Markov chain models.
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A novel method was introduced to predict protein subcellular locations from sequences. Using sequence data, this method achieved a prediction accuracy higher than previous methods based on the amino acid composition. For three subcellular locations in a prokaryotic organism, the overall prediction accuracy reached 89.1%. For eukaryotic proteins, prediction accuracies of 73.0% and 78.7% were attained within four and three location categories, respectively. These results demonstrate the applicability of this relative simple method and possible improvement of prediction for the protein subcellular location. (+info)
The cost-effectiveness of endovascular repair versus open surgical repair of abdominal aortic aneurysms: A decision analysis model.
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PURPOSE: Endovascular repair (EVR) is a less-invasive method for the treatment of abdominal aortic aneurysms (AAAs) as compared with open surgical repair (OSR). The potential benefits of EVR include increased patient acceptance, less resource utilization, and cost savings. This study was designed to determine whether the EVR of AAAs is a cost-effective alternative to OSR. METHODS: A cost-effectiveness analysis was performed using a Markov decision analysis model to compute long-term survival rates in quality-adjusted life years and lifetime costs for a hypothetical cohort of patients who underwent either OSR or EVR. Probability estimates of the different outcomes of the two alternative strategies were made on the basis of a review of the literature. The average costs of (1) the immediate hospitalization ($16,016 for OSR, $20,083 for EVR), (2) the complications that resulted from each procedure, (3) the subsequent interventions, and (4) the surveillance protocol were determined on the basis of average resource utilization as reported in the literature and from our hospital's cost accounting system. Our measure of outcome was the cost-effectiveness ratio. RESULTS: For our base-case analysis (70-year-old men with 5-cm AAAs), EVR was cost-effective with a cost-effectiveness ratio of $22,826-society usually is willing to pay for interventions with cost-effectiveness ratios of less than $60,000 (eg, cost-effectiveness ratios for coronary artery bypass grafting and dialysis are $9500 and $54,400, respectively). This conclusion did not vary significantly with increases in procedural costs for EVR (ie, if the cost of the endograft increased from $8000 to $12,000, EVR remained cost-effective with a cost-effectiveness ratio of $32,881). The cost-effectiveness of EVR was critically dependent on EVR producing a large reduction in the combined mortality and long-term morbidity rate (stroke, dialysis-dependent renal failure, major amputation, myocardial infarction) as compared with OSR (ie, a reduction in the combined mortality and long-term morbidity rate of OSR from 9.1% to 4.7% made EVR no longer cost-effective). CONCLUSION: Despite the high cost of new technology and the need for close postoperative surveillance, EVR is a cost-effective alternative for the repair of AAAs. However, the cost-effectiveness of this new technology is critically dependent on its potential to reduce morbidity and mortality rates as compared with OSR. EVR may not be cost-effective in medical centers where OSR can be performed with low risk. (+info)
Should endovascular surgery lower the threshold for repair of abdominal aortic aneurysms?
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PURPOSE: Because endovascular repair of abdominal aortic aneurysms (AAAs) is less invasive, some investigators have suggested that this increasingly popular technique should broaden the indications for elective AAA repair. The purpose of this study was to calculate quality-adjusted life expectancy rates after endovascular and open AAA repair and to estimate the optimal diameter for elective AAA repair in hypothetical cohorts of patients at average risk and at high risk. METHODS: A Markov decision analysis model was used in this study. Assumptions were made on the basis of published reports and included the following: (1) the annual rupture rate is a continuous function of the AAA diameter (0% for <4 cm, 1% for 4.5 cm, 11% for 5.5 cm, and 26% for 6.5 cm); (2) the operative mortality rate is 1% for endovascular repair (excluding the risk of conversion to open repair) and 3.5% for open repair at age 70 years; and (3) immediate endovascular-to-open conversion risk is 5%, and late conversion rate is 1% per year. The main outcome measure in this study was the benefit of AAA repair in quality-adjusted life years (QALYs). The optimal threshold size (the AAA diameter at which elective repair maximizes benefit) was measured in centimeters. RESULTS: The benefit of endovascular repair is consistently greater than that of open repair, but the additional benefit is small-0.1 to 0.4 QALYs. For men in average health with gradually enlarging AAAs with initial diameters of 4 cm, endovascular surgery reduces the optimal threshold diameter by very little: from 4.6 to 4.6 cm (no change) at age 60 years, from 4.8 to 4.7 cm at age 70 years, and from 5.1 to 4.9 cm at age 80 years. For older men in poor health, endovascular surgery reduces the optimal threshold diameter substantially (8.1 to 5.7 cm at age 80 years), but the benefit of repair in this population is small (0.2 QALYs). CONCLUSION: For most patients, the indications for AAA repair are changed very little by the introduction of endovascular surgery. Only for older patients in poor health does endovascular surgery substantially lower the optimal threshold diameter for elective AAA repair. (+info)
Interpolated markov chains for eukaryotic promoter recognition.
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MOTIVATION: We describe a new content-based approach for the detection of promoter regions of eukaryotic protein encoding genes. Our system is based on three interpolated Markov chains (IMCs) of different order which are trained on coding, non-coding and promoter sequences. It was recently shown that the interpolation of Markov chains leads to stable parameters and improves on the results in microbial gene finding (Salzberg et al., Nucleic Acids Res., 26, 544-548, 1998). Here, we present new methods for an automated estimation of optimal interpolation parameters and show how the IMCs can be applied to detect promoters in contiguous DNA sequences. Our interpolation approach can also be employed to obtain a reliable scoring function for human coding DNA regions, and the trained models can easily be incorporated in the general framework for gene recognition systems. RESULTS: A 5-fold cross-validation evaluation of our IMC approach on a representative sequence set yielded a mean correlation coefficient of 0.84 (promoter versus coding sequences) and 0.53 (promoter versus non-coding sequences). Applied to the task of eukaryotic promoter region identification in genomic DNA sequences, our classifier identifies 50% of the promoter regions in the sequences used in the most recent review and comparison by Fickett and Hatzigeorgiou ( Genome Res., 7, 861-878, 1997), while having a false-positive rate of 1/849 bp. (+info)
Prevention of vertical transmission of HIV: analysis of cost effectiveness of options available in South Africa.
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OBJECTIVE: To assess the cost effectiveness of vertical transmission prevention strategies by using a mathematical simulation model. DESIGN: A Markov chain model was used to simulate the cost effectiveness of four formula feeding strategies, three antiretroviral interventions, and combined formula feeding and antiretroviral interventions on a cohort of 20 000 pregnancies. All children born to HIV positive mothers were followed up until age of likely death given current life expectancy and a cost per life year gained calculated for each strategy. SETTING: Model of working class, urban South African population. RESULTS: Low cost antiretroviral regimens were almost as effective as high cost ones and more cost effective when formula feeding interventions were added. With or without formula feeding, low cost antiretroviral interventions were likely to save lives and money. Interventions that allowed breast feeding early on, to be replaced by formula feeding at 4 or 7 months, seemed likely to save fewer lives and offered poorer value for money. CONCLUSIONS: Antiretroviral interventions are probably cost effective across a wide range of settings, with or without formula feeding interventions. The appropriateness of formula feeding was highly cost effective only in settings with high seroprevalence and reasonable levels of child survival and dangerous where infant mortality was high or the protective effect of breast feeding substantial. Pilot projects are now needed to ensure the feasibility of implementation. (+info)
End-stage renal disease in Canada: prevalence projections to 2005.
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BACKGROUND: The incidence and prevalence of end-stage renal disease (ESRD) have increased greatly in Canada over the last 2 decades. Because of the high cost of therapy, predicting numbers of patients who will require dialysis and transplantation is necessary for nephrologists and health care planners. METHODS: The authors projected ESRD incidence rates and therapy-specific prevalence by province to the year 2005 using 1981-1996 data obtained from the Canadian Organ Replacement Register. The model incorporated Poisson regression to project incidence rates, and a Markov model for patient follow-up. RESULTS: Continued large increases in ESRD incidence and prevalence were projected, particularly among people with diabetes mellitus. As of Dec. 31, 1996, there were 17,807 patients receiving renal replacement therapy in Canada. This number was projected to climb to 32,952 by the end of 2005, for a relative increase of 85% and a mean annual increase of 5.8%. The increased prevalence was projected to be greatest for peritoneal dialysis (6.0% annually), followed by hemodialysis (5.9%) and functioning kidney transplant (5.7%). The projected annual increases in prevalence by province ranged from 4.4%, in Saskatchewan, to 7.5%, in Alberta. INTERPRETATION: The projected increases are plausible when one considers that the incidence of ESRD per million population in the United States and other countries far exceeds that in Canada. The authors predict a continued and increasing short-fall in resources to accommodate the expected increased in ESRD prevalence. (+info)
A systematic review of cost-effectiveness research of stroke evaluation and treatment.
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BACKGROUND AND PURPOSE: This work was undertaken to review research addressing the cost-effectiveness of stroke-related diagnostic, preventive, or therapeutic interventions. METHODS: We performed searches of MEDLINE, Excerpta Medica online, HealthSTAR, and Sciences Citation Index Expanded and examined the reference lists of the studies and reviews obtained. From these, we selected studies that reported an incremental analysis of cost per effect, in which the effect measure was life-years or quality-adjusted life-years. We abstracted data from each study using a standardized reporting form. Twenty-six articles met the eligibility criteria and were included in the review. RESULTS: The methodological quality of the articles reviewed has improved compared with previously reported. Many stroke evaluation and treatment policies may result in benefits to health that are considered worth their cost. Some interventions were considered cost-ineffective (anticoagulation in low-risk nonvalvular atrial fibrillation and surveillance with duplex ultrasound after endarterectomy). Different studies addressing the cost-effectiveness of screening asymptomatic carotid stenosis resulted in strikingly divergent conclusions, from being cost-effective to being detrimental. Other studies omitted important costs that, if included, would likely have had profound impact on their cost-effectiveness estimates. CONCLUSIONS: Given the divergent conclusions drawn from studies addressing similar questions, it may be premature to use the results of cost-effectiveness research in developing stroke policy and practice guidelines. Successful implementation of such evaluations in the care of patients with stroke will depend on further standardization of methodology and critical appraisal of reported findings. (+info)
Cost-effectiveness of screening compared to case-finding approaches to tuberculosis in long-term care facilities for the elderly.
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BACKGROUND: To determine if the more interventionist approach of screening with the tuberculin test and chemoprophylaxis for high-risk positive reactors to control tuberculosis in long-term care facilities is cost-effective when compared to the case-finding and treatment approach. METHOD: A decision-analysis model was designed wherein systematic screening with the tuberculin skin test of all elderly patients newly admitted to facilities was compared to public health interventions restricted to investigation of cases and contacts with symptoms of tuberculosis after suspected exposure. Differences in life-years (LY), quality-adjusted life-years (QALY), cost per QALY and LY gained, annual cost per 1000 institutional patients were calculated in a health-care system perspective. RESULTS: In every situation analysed, screening and chemoprophylaxis were more effective. The cost per LY gained was within an acceptable range: $3437 per LY with a 0.6% nosocomial transmission rate and $7552 per LY when no nosocomial transmission was postulated. CONCLUSION: Screening plus chemoprophylaxis for high-risk reactors is more cost-effective than case-finding. This holds even when nosocomial transmission is assumed not to occur in facilities. (+info)