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Biomedical subjects

M D Krahn

Publications and source records attributed to M D Krahn.

18 recordsLinked to original sources
PubMed2001

Initial bone marrow aspiration in childhood idiopathic thrombocytopenia: decision analysis.

PURPOSE: Bone marrow aspiration (BMA) is routinely performed before starting steroid therapy in children with idiopathic thrombocytopenia, primarily to rule out leukemia. METHODS: A decision tree for the initial management of a child older than age 6 months, presenting with idiopathic thrombocytopenia, without blasts on the peripheral smear was constructed. The three strategies are: 1) initial BMA in all patients; 2) initial BMA only in patients at high risk; and 3) empiric therapy for all patients without initial BMA. High-risk criteria include any of: platelet count >50 x 10(9)/L; hemoglobin <100 g/L (age younger than 12 months) or <110 g/L (age older than 12 months): white blood cell count <5 x 10(9)/L (younger than 6 years) or <4 x 10(9)/L (older than 6 years); or absolute neutrophil count <1.5 x 10(9)/L (younger than 6 years) or <2 x 10(9)/L (older than 6 years). The results are expressed as quality-adjusted life years (QALYs), a measure that estimates the overall life expectancy in years for patients receiving a particular treatment strategy, corrected for the patient's quality of life. RESULTS: The base case results are: 1) BMA all = 69.649 QALYs; 2) high-risk BMA = 69.652 QALYs; and 3) empiric therapy = 69.644 QALYs. These results indicate a three-way toss-up because there is less than a 4-day quality-adjusted difference (0.01) between strategies. CONCLUSION: This study indicates that the initial BMA does not significantly change the overall QALYs of a child presenting with thrombocytopenia and, consequently, is not mandatory in every patient before starting steroids.

Adolescent↗
PubMed2000

Predicting preterm birth: a cost-effectiveness analysis.

OBJECTIVE: The objective of this study was to compare the cost-effectiveness of 9 strategies for the management of threatened preterm labor. STUDY DESIGN: We derived 6 management options from the literature. These were (1) to treat all women with tocolytics and corticosteroids ("treat all"); (2) to treat all women while awaiting results of the "traditional" fetal fibronectin test results, then discontinue treatment on those with negative results; (3) to treat only those with abnormal cervical length measurements as detected by ultrasonography; (4) to treat only those with abnormal "rapid" fetal fibronectin test results; (5) to perform rapid fetal fibronectin testing and cervical length measurements and treat those with a positive result on either or both; (6) not to treat any women ("treat none"). To assess the contributions of tocolytics and corticosteroids to our outcomes, we analyzed 3 additional treatment options: (7) to treat all women with outpatient corticosteroids but not give tocolytics, (8) to administer corticosteroids to all but give tocolytics only to those with abnormal rapid fetal fibronectin test results, and (9) to administer corticosteroids to all but give tocolytics only to those with abnormal cervical length. We used decision analytic techniques to perform a cost-effectiveness analysis. RESULTS: A decision tree was constructed on the basis of these strategies. We reviewed the literature to derive all probability information. We derived sensitivity and specificity for delivery <37 weeks for fetal fibronectin and for abnormal cervical length. Outcomes of interest were respiratory distress syndrome and neonatal death. We derived cost variables from institutional statistics and from values quoted in the literature. Total costs, cases of respiratory distress syndrome, neonatal deaths, and cost-effectiveness ratios were calculated for each of the strategies. We conducted sensitivity analyses on all variables. Universal administration of outpatient corticosteroids was the least expensive option, but it resulted in more cases of respiratory distress syndrome and deaths than "treat all." Rapid fetal fibronectin plus corticosteroids, traditional fetal fibronectin, and cervical length plus corticosteroids were the next least expensive options and resulted in numbers of cases of respiratory distress syndrome and deaths that were similar to those in the "treat all" strategy. The "rapid" fetal fibronectin test, cervical length measurement, rapid fetal fibronectin test plus cervical length measurement, and "treat none" strategies resulted in more respiratory distress syndrome, more deaths, and higher costs. Treating all patients resulted in the fewest number of cases of respiratory distress syndrome and deaths but the greatest costs. CONCLUSION: Risk prediction strategies with the fetal fibronectin assay or corticosteroids plus rapid fetal fibronectin testing or cervical length assessment may offer cost savings compared with treatment of all women with threatened preterm labor and may prevent similar numbers of cases of respiratory distress syndrome and neonatal deaths.

Adrenal Cortex Hormones↗
PubMed2000

Prostate specific antigen response to mitoxantrone and prednisone in patients with refractory prostate cancer: prognostic factors and generalizability of a multicenter trial to clinical practice.

PURPOSE: We determine prostate specific antigen (PSA) response and durability, and prognostic factors associated with response and survival in patients with symptomatic hormone refractory prostate cancer treated with mitoxantrone and prednisone at a single institution. We then compare the results with those of a randomized phase III clinical trial. MATERIALS AND METHODS: A retrospective review of all 133 patients treated with mitoxantrone and prednisone at Princess Margaret Hospital since 1994 was performed. PSA response and duration, and overall survival were determined as well as the influence of baseline factors on these outcome parameters. Results were compared to those for patients randomized to receive mitoxantrone and prednisone in the Canadian clinical trial which demonstrated palliative benefit of this regimen. RESULTS: Patients treated after trial closure had shorter survival (p = 0.003) but represented a poorer prognosis cohort. PSA response of the trial and post-trial cases was 34% and 28%, respectively (p = 0.36), and median duration of response was 118 and 175 days or greater, respectively. Factors predictive of PSA response in the non-trial cohort were longer time from diagnosis of prostate cancer (p = 0. 027) and higher baseline PSA (p = 0.013). Factors predictive of increased survival in both groups were younger age (p <0.04), better baseline Eastern Cooperative Oncology Group performance status (p <0. 02), and higher hemoglobin (p </=0.05) and PSA response (p <0.0001). Gleason score was not predictive of response or survival. CONCLUSIONS: Although patients treated outside of the trial had poorer prognostic features, rates of PSA response to mitoxantrone and prednisone were comparable. Factors predictive of survival were similar in the 2 cohorts. Results of the randomized trial are generalizable to clinical practice.

Adenocarcinoma↗
PubMed2000

Significance of the CAG repeat polymorphism of the androgen receptor gene in prostate cancer progression.

PURPOSE: The CAG repeat polymorphism of the androgen receptor gene has been associated with an increased prostate cancer risk, and the repeat length correlated with cancer stage and grade at presentation. Men with an allele length of </= 18 CAG repeats have a 2-fold increase in risk for high-stage or high-grade prostate cancer, compared with patients with a longer CAG repeat. We examined the significance of the CAG repeat polymorphism of the androgen receptor gene for predicting prostate cancer progression among 318 patients treated by radical prostatectomy for clinically localized prostate cancer between 1987 and 1994. MATERIALS AND METHODS: Leukocyte DNA was collected and genotyping of the CAG repeat polymorphism was performed using a PCR-based direct sequencing method. Risk ratios were calculated for developing biochemical recurrence for patients associated with an allele length of </= 18 CAG repeats, compared with patients with an allele length of >18 CAG repeats, controlling for grade, stage and serum PSA level at diagnosis using Cox proportional hazard modeling. RESULTS: Overall, the CAG repeat allele was not predictive of recurrence; tumor grade, stage and PSA level at diagnosis were the only predictors of recurrence in a multivariate analysis. However, for patients at low risk for recurrence (Gleason score 2 to 6, stage pT2, and PSA </= 10 ng./ml.), the relative risk of recurrence associated with an allele of </= 18 CAG repeats was 8.07 (95% C.I., 2.02 to 32.2, p = 0.004), compared with patients with an allele length of >18 CAG repeats. In contrast, for patients at high risk of recurrence (Gleason score >/= 7, stage pT3/4, or PSA >10 ng./ml.), the relative risk associated with the </= 18 CAG repeat allele was 0.72 (95% C.I., 0.33 to 1.57, p = 0.41), compared with patients with the >18 CAG repeat allele. CONCLUSIONS: The length of the CAG repeat polymorphism of the androgen receptor gene may be important for prostate cancer recurrence among patients who are otherwise at low risk for recurrence after radical prostatectomy. These findings have potential implications for patient selection for adjuvant treatment, and for the development of novel treatments.

Alleles↗
PubMed1999

Direct costs of coronary artery bypass grafting in patients aged 65 years or more and those under age 65.

BACKGROUND: Over the past 20 years, there have been marked increases in rates of coronary artery bypass grafting (CABG) among older people in Canada. The objectives of this study were to accurately estimate the direct medical costs of CABG in older patients (age 65 years or more) and to compare CABG costs for this age group with those for patients less than 65 years of age. METHODS: Direct medical costs were estimated from a sample of 205 older and 202 younger patients with triple-vessel or left main coronary artery disease who underwent isolated CABG at The Toronto Hospital, a tertiary care university-affiliated hospital, between Apr. 1, 1991, and Mar. 31, 1992. Costs are expressed in 1992 Canadian dollars from a third-party payer perspective. RESULTS: The mean costs of CABG in older and younger patients respectively were $16,500 and $15,600 for elective, uncomplicated cases, $23,200 and $19,200 for nonelective, uncomplicated cases, $29,200 and $20,300 for elective, complicated cases, and $33,600 and $23,700 for nonelective, complicated cases. Age remained a significant determinant of costs after adjustment for severity of heart disease and for comorbidity. Between 59% and 91% of the cost difference between older and younger patients was accounted for by higher intensive care unit and ward costs. INTERPRETATION: CABG was more costly in older people, especially in complicated cases, even after an attempt to adjust for severity of disease and comorbidity. Future studies should attempt to identify modifiable factors that contribute to longer intensive care and ward stays for older patients.

Age Factors↗
PubMed1999

Current and projected annual direct costs of screening asymptomatic men for prostate cancer using prostate-specific antigen.

BACKGROUND: Concern over the cost of screening for asymptomatic prostate cancer by means of prostate-specific antigen (PSA) testing has played an important role in PSA screening policy. However, little is known about the true costs of current PSA screening in Canada and how costs may change in the future. METHODS: The authors performed a cost identification study from the perspective of provincial ministries of health. They used data from published reports, hospital discharge data, claims data from several provinces, a laboratory survey, a national survey of knowledge, attitudes and beliefs about screening, a provincial cancer registry and expert opinion to estimate current first-year screening costs. Using demographic data from Statistics Canada and various scenarios regarding changes in screening patterns, the authors derived estimates of the future costs of PSA screening. RESULTS: In 1995 PSA screening cost an estimated $45 million (range $40 million to $84 million). Treatment accounted for over 61% of total costs, whereas screening, diagnosis and staging accounted for 35%. Screening all eligible men in Canada in 1995 would have cost $317 million (range $356 million to $691 million), more than the costs of all prostate cancer care in that year. Annual recurrent screening for all eligible men in 2005 would cost $219 million (range $208 million to $412 million). Projections from existing trends suggest that annual costs of PSA screening in 2000 are likely to increase from the estimated $45 million to approximately $66 million (range $59 million to $126 million). INTERPRETATION: PSA screening is costly, but even universal screening would consume a smaller share of national health expenditures than previous studies have suggested. Costs attributable to PSA screening may increase in the future owing to changes in utilization patterns and demographic shifts.

Aged↗
PubMed1998

Economic evaluation of chemotherapy with mitoxantrone plus prednisone for symptomatic hormone-resistant prostate cancer: based on a Canadian randomized trial with palliative end points.

PURPOSE: To evaluate the economic consequences of the use of chemotherapy in patients with symptomatic hormone-resistant prostate cancer (HRPC) in the context of a previously published Canadian open-label, phase III, randomized trial with palliative end points. PATIENTS AND METHODS: The trial randomized 161 patients to initial treatment with mitoxantrone and prednisone (M + P) or to prednisone alone (P) and showed better palliation with M + P. There was no significant difference in survival. A detailed retrospective chart review was performed of resources used from randomization until death of 114 of 161 patients enrolled at the three largest centers: these included hospital admissions, outpatient visits, investigations, therapies (which included all chemotherapy and radiation), and palliative care. Cancer center and community hospital costs were calculated by using the hotel approximation method and case costing from the Ontario Case Cost Project, respectively. Cost-utility analysis was performed by transforming the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 global quality-of-life item measured every 3 weeks on trial to an estimate of utility, and extending the last known value through to death or last follow-up. RESULTS: The mean total cost until death or last follow-up by intention-to-treat was M + P CDN $27,300; P CDN $29,000. The 95% confidence intervals on the observed cost difference ranged from a saving of $9,200 for M + P (with palliative benefit) to an increased cost of $5,800 for M + P. The major proportion of cost (M + P 53% v P 66%; CDN $14,500 v $19,100) was for inpatient care. Initial M + P was consistently less expensive in whichever time period was used to compare costs. Cost-utility analysis showed M + P to be the preferred strategy with an upper 95% confidence interval for the incremental cost-utility ratio of CDN $19,700 per quality-adjusted life-year (QALY). CONCLUSION: A treatment that reduces symptoms and improves quality of life has the potential to reduce costs in other areas. Economic factors should not influence the clinical decision as to whether to use M + P in a symptomatic patient.

Canada↗
PubMed1996

Direct and indirect costs of asthma in Canada, 1990.

OBJECTIVE: To calculate the direct and indirect costs of asthma in Canada. DESIGN: Cost-of-illness study. SETTING: Canada. PATIENTS: All Canadians receiving inpatient or outpatient care for asthma in 1990. OUTCOME MEASURES: Direct costs incurred by inpatient care, emergency services, physician and nursing services, ambulance use, drugs and devices, outpatient diagnostic tests, research and education. Indirect costs from productivity loss due to absence from work, inability to to perform housekeeping activities, need to care for children with asthma who were absent from school, time spent travelling and waiting for medical care, and premature death from asthma. All costs are in 1990 Canadian dollars. RESULTS: Depending on assumptions, the total cost of asthma was estimated to be between $504 million and $648 million. Direct costs were $306 million. The single largest component of direct costs was the cost of drugs ($124 million). The largest component of indirect costs was illness-related disability ($76 million). CONCLUSIONS: Annual costs of treating asthma are comparable to the individual cost of infectious diseases, hematological diseases, congenital defects, perinatal illnesses, home care and ambulance services. Asthma costs may increase in the future, given current morbidity and mortality trends. Further evaluation of the effectiveness and cost-effectiveness of available asthma interventions in addition to aggregate cost data are required to determine whether resource allocation for the treatment of asthma can be improved.

Absenteeism↗
PubMed1994

Screening for prostate cancer. A decision analytic view.

OBJECTIVE: To determine the clinical and economic effects of screening for prostate cancer with prostate-specific antigen (PSA), transrectal ultrasound (TRUS), and digital rectal examination (DRE). DESIGN: Decision analytic cost-utility analysis comparing four screening strategies with a strategy of not screening. We assumed that the cancer detection rate and stage distribution were predicted by each combination of tests and that localized cancer was treated with radical prostatectomy. For each strategy, we calculated life expectancy, quality-adjusted life expectancy (QALE), and cost-utility ratios for unselected and high-prevalence populations. DATA: Probabilities and rates for clinical events were gathered from published data. We assessed utilities by the time-trade-off method using urologists, radiation oncologists, and internists as subjects. The Clinical Cost Manager at the New England Medical Center provided cost data. RESULTS: In unselected men between the ages of 50 and 70 years, screening with PSA or TRUS prolonged unadjusted life expectancy but diminished QALE. Screening with DRE alone yielded no reduction in mortality at any age. All programs increased costs. Results were sensitive only to assumptions about the efficacy of treatment. In high-prevalence populations, screening produced a similar pattern: gains in unadjusted life expectancy, losses in QALE, and increased costs. CONCLUSIONS: Our analysis does not support using PSA, TRUS, or DRE to screen asymptomatic men for prostatic cancer. Screening may result in poorer health outcomes and will increase costs dramatically. Assessment of comorbidity, risk attitude, and valuation of sexual function may identify individuals who will benefit from screening, but selecting high-prevalence populations will not improve the benefit of screening.

Aged↗
PubMedDate not supplied

Primer on medical decision analysis: Part 1--Getting started.

This paper is Part 1 of a five-part series covering practical issues in the performance of decision analysis. The intended audience is individuals who are learning how to perform decision analyses, not just read them. The series assumes familiarity with the basic concepts of decision analysis. It imparts many of the recommendations the authors have learned in teaching a one-semester course in decision analysis to graduate students. Part 1 introduces the topic and covers questions such as choosing an appropriate question, determining the tradeoff between accuracy and simplicity, and deciding on a time frame.

Decision Support Techniques↗
PubMedDate not supplied

Primer on medical decision analysis: Part 2--Building a tree.

This part of a five-part series covering practical issues in the performance of decision analysis outlines the basic strategies for building decision trees. The authors offer six recommendations for building and programming decision trees. Following these six recommendations will facilitate performance of the sensitivity analyses required to achieve two goals. The first is to find modeling or programming errors, a process known as "debugging" the tree. The second is to determine the robustness of the qualitative conclusions drawn from the analysis.

Decision Making, Computer-Assisted↗
PubMedDate not supplied

Primer on medical decision analysis: Part 3--Estimating probabilities and utilities.

This paper describes how to estimate probabilities and outcome values for decision trees. Probabilities are usually derived from published studies, but occasionally are derived from existing databases, primary data collection, or expert judgment. Outcome values represent quantitative estimates of the desirability of the outcome states, and are often expressed as utility values between 0 and 1. Utility values for different health states can be derived from the published literature, from direct measurement in appropriate subjects, or from expert opinion. Methods for assigning utilities to complex outcome states are described, and the concept of quality-adjusted life years is introduced.

Biopsy↗
PubMedDate not supplied

Primer on medical decision analysis: Part 4--Analyzing the model and interpreting the results.

This paper is the fourth of a five-part series that describes the principles of construction and evaluation of valid decision models. In this review, the authors describe the key principles of detecting and eliminating structural and programming errors in decision trees (debugging). In addition, they offer guidelines to facilitate the interpretation of analytic results of decision models.

Data Interpretation, Statistical↗
PubMedDate not supplied

Primer on medical decision analysis: Part 5--Working with Markov processes.

Clinical decisions often have long-term implications. Analysis encounter difficulties when employing conventional decision-analytic methods to model these scenarios. This occurs because probability and utility variables often change with time and conventional decision trees do not easily capture this dynamic quality. A Markov analysis performed with current computer software programs provides a flexible and convenient means of modeling long-term scenarios. However, novices should be aware of several potential pitfalls when attempting to use these programs. When deciding how to model a given clinical problem, the analyst must weigh the simplicity and clarity of a conventional tree against the fidelity of a Markov analysis. In direct comparisons, both approaches gave the same qualitative answers.

Biopsy↗
PubMedDate not supplied

Guidelines for verbal presentations of medical decision analyses.

Individuals new to decision analysis often have difficulty with oral presentations of original research projects. This article provides general guidelines on how to present effectively. Points include: 1) articulating the research issue, 2) reviewing current beliefs, 3) portraying the study question, 4) listing the main assumptions, 5) presenting the base-case analysis, 6) showing sensitivity analyses, and 7) discussing the implications. The guidelines comment on what to exclude from presentation and how best to handle audience questions. The guidelines do not replace general instruction in public speaking (or rigorous training in decision analysis), but may help students present research projects effectively.

Communication↗