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PubMed1998

DNA repair proficiency: a potential marker for identification of high risk members in breast cancer families.

Breast cancer is the single largest cancer and causes the high rate of cancer mortality among women. A positive family history of breast cancer is recognized as one of the major risk factors for this disease. The present study evaluates bleomycin (BLM)-induced chromosome sensitivity analysis in breast cancer families which provides indirectly a measure of the DNA repair defect of each person. BLM sensitivity assay on cultured lymphocytes of 36 familial breast cancer patients, their 85 first or second degree female relatives, 36 sporadic breast cancer patients and 40 age- and sex-matched controls (without any family history of cancer) were carried out to measure interindividual variation in their DNA repair capacity through mutagen-induced chromosome sensitivity analysis. Fifty percent of familial breast cancer patients and seven unaffected relatives showed hypersensitivity. Compared to hyposensitive relatives these seven subjects may be considered as high risk individuals.

Adolescent↗
PubMed1992

How useful is the rheumatoid factor? An analysis of sensitivity, specificity, and predictive value.

BACKGROUND: The rheumatoid factor (RF) is frequently ordered in an effort to detect disease, yet its diagnostic utility has not been thoroughly examined. To determine the test's sensitivity, specificity, positive predictive value, and negative predictive value, we analyzed tests ordered in our institution. METHODS: We performed a retrospective analysis of all 86 patients with a positive RF over a 6-month period identified consecutively soon after the test was ordered. A similar analysis was applied to 86 seronegative patients selected at random from a total seronegative population of 477 during the same period. The patients represented the primary care and subspecialty practices and inpatient wards of a 504-bed university teaching hospital. RESULTS: A positive RF result was strongly associated with rheumatoid arthritis or another rheumatic disease. For rheumatoid arthritis, sensitivity = 0.28 and specificity = 0.87, while for any rheumatic disease, sensitivity = 0.29 and specificity = 0.88. The positive predictive values for rheumatoid arthritis and any rheumatic disease were 0.24 and 0.34, respectively, and the negative predictive values were 0.89 and 0.85, respectively. Seropositive patients were slightly older (55 vs 49 years old), but the incidence of false-positive RFs among the elderly (69%) was not significantly higher than among younger patients (65%). The cost per true-positive RF result was $563. CONCLUSIONS: In this study, most positive RF results were not helpful since the majority represented false-positive results. The low positive predictive value of the RF casts doubt on the utility of the RF in the diagnostic evaluation of patients. Contrary to traditional clinical expectations, the diagnostic utility of the RF may be greatest when it is negative. However, the subset of patients with seronegative rheumatic disease reduces the test's power to exclude such disorders even when the RF is negative. Given the test's limitations, clinicians should reconsider their expectations when ordering an RF. The utility of the RF may improve if it is ordered more selectively.

Aged↗
PubMed2005

Computational study on use of single-point analysis method for quantitating local cerebral blood flow in mice.

The benefits of a mouse model are efficiency and availability of transgenics/ knockouts. Quantitation of cerebral blood in small animals is difficult because the cannulation procedure may introduce errors. The [14C]-iodoantipyrine autoradiography (IAP) method requires both the tissue concentration and the time course of arterial concentration of the [14C] radioactive tracer. A single point-analysis technique was evaluated for measuring blood flow in mice (30 g +/- 0.3 g; n = 11) by using computational models of sensitivity analysis, which quantitates relationships between the predictions of a model and its parameters. Using [14C]-IAP in conjunction with mathematical algorithms and assumed arterial concentration-versus-time profiles, cortical blood flow was deduced from single-point measurements of the arterial tracer concentration. The data showed the arterial concentration profile that produced the most realistic blood flows (1.6 +/- 0.4; mean +/- SD, ml/g/min) was a profile with a ramp time of 30 sec followed by a constant value over the remaining time period of 30 sec. Sensitivity analysis showed that the total experimental time period was a more important parameter than the lag period and the ramp period. Thus, it appears that the accuracy of the assumption of linearly increasing arterial concentration depends on the experimental time period and the final arterial [14C]-iodoantipyrine concentration.

Algorithms↗
PubMed1999

Solid state assay of ranitidine HCl as a bulk drug and as active ingredient in tablets using DRIFT spectroscopy with artificial neural networks.

PURPOSE: A new, simple, sensitive and rapid method was developed to analyse the polymorphic purity of crystalline ranitidine-HCI as a bulk drug and from a tablet formulation. METHODS: Diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy was combined with Artificial Neural Networks (ANNs) as a data modelling tool. A standard feed-forward network, with backpropagation rule and with single hidden layer architecture was chosen. Reduction and transformation of the spectral data enhanced the ANN performance and reduced the complexity of the ANNs model. Spectral intensities from 1738 wavenumbers were reduced into 173 averaged spectral values. These 173 values were used as inputs for the ANN. Following a sensitivity analysis the number of inputs was reduced to 30, or 35, these being the input windows which had most effect on the output of the ANN. RESULTS: For the bulk drug assay, the ANN model had 30 inputs selected from a sensitivity analysis, one hidden layer, and two output neurons, one for the percentage of each ranitidine hydrochloride crystal form. The model could simultaneously distinguish between crystal forms and quantify them enabling the physical purity of the bulk drug to be checked. For the tablet assay, the ANN model had 173 averaged spectral values as the inputs, one hidden layer and five output neurons, two for the percentage of the two ranitidine hydrochloride crystal forms and three more outputs for tablet excipients and additives. The ANN was able to solve the problem of overlapping peaks and it successfully identified and quantified all components in tablet formulation with reasonable accuracy. CONCLUSIONS: Some of the advantages over conventional analytical methods include simplicity, speed and good selectivity. The results from DRIFT spectral quantification study show the benefits of the neural network approach in analysing spectral data.

Anti-Ulcer Agents↗
PubMedDate not supplied

A sensitive noninvasive analysis of Pt in external tissues. Followup of Pt deposition following cisplatin treatment.

Noninvasive analysis of heavy elements in external tissues by diagnostic-x-ray spectrometry (DXS) is presented. Pt can be detected accurately with sensitivity below 1 microgram/g wet weight of tissue. In the present paper the possibility to monitor Pt accumulation and clearance in the external tissues of cancer patients treated with cisplatin [Cis-diamminedichloroplatinum (II)-cDDP] chemotherapy is reported. The DXS method is based on x-ray fluorescence analysis. Heavy elements in the small skin area of interest are analyzed by their excitation with a monochromatic soft x-ray beam of 14.6 KeV. Spectral L lines of heavy metals such as Pt are detected with minimum interference by other elements in the tissues. Skin Pt levels up to about 6 micrograms/g were observed following several courses of cDDP treatment. The Pt seemed to be homogeneously distributed in different skin areas with similar levels in the dermis and epidermis. The rate of clearance of Pt from the skin (50% in about 30 days) was slower by three orders of magnitude than its clearance from plasma. Further studies may use DXS to establish the accurate kinetics of Pt deposition and clearance in tissues of cDDP treated patients, as well as the exact relation between tissue Pt levels and the development of the drug related late complications.

Biophysical Phenomena↗
PubMedDate not supplied

Decision analysis with cumulative prospect theory.

BACKGROUND: Individuals sometimes express preferences that do not follow expected utility theory. Cumulative prospect theory adjusts for some phenomena by using decision weights rather than probabilities when analyzing a decision tree. METHODS: The authors examined how probability transformations from cumulative prospect theory might alter a decision analysis of a prophylactic therapy in AIDS, eliciting utilities from patients with HIV infection (n = 75) and calculating expected outcomes using an established Markov model. They next focused on transformations of three sets of probabilities: 1) the probabilities used in calculating standard-gamble utility scores; 2) the probabilities of being in discrete Markov states; 3) the probabilities of transitioning between Markov states. RESULTS: The same prophylaxis strategy yielded the highest quality-adjusted survival under all transformations. For the average patient, prophylaxis appeared relatively less advantageous when standard-gamble utilities were transformed. Prophylaxis appeared relatively more advantageous when state probabilities were transformed and relatively less advantageous when transition probabilities were transformed. Transforming standard-gamble and transition probabilities simultaneously decreased the gain from prophylaxis by almost half. Sensitivity analysis indicated that even near-linear probability weighting transformations could substantially alter quality-adjusted survival estimates. CONCLUSION: The magnitude of benefit estimated in a decision-analytic model can change significantly after using cumulative prospect theory. Incorporating cumulative prospect theory into decision analysis can provide a form of sensitivity analysis and may help describe when people deviate from expected utility theory.

AIDS-Related Opportunistic Infections↗
PubMed2003

The cost-effectiveness of cyclooxygenase-2 selective inhibitors in the management of chronic arthritis.

BACKGROUND: Rofecoxib and celecoxib (coxibs) effectively treat chronic arthritis pain and reduce ulcer complications by 50% compared with nonselective nonsteroidal anti-inflammatory drugs (NSAIDs). However, their absolute risk reduction is small and the cost-effectiveness of treatment is uncertain. OBJECTIVE: To determine whether the degree of risk reduction in gastrointestinal complications by coxibs offsets their increased cost compared with a generic nonselective NSAID. DESIGN: Cost-utility analysis. DATA SOURCES: Systematic review of MEDLINE and published abstracts. TARGET POPULATION: Patients with osteoarthritis or rheumatoid arthritis who are not taking aspirin and who require long-term NSAID therapy for moderate to severe arthritis pain. PERSPECTIVE: Third-party payer. INTERVENTIONS: Naproxen, 500 mg twice daily, and coxib, once daily. Patients intolerant of naproxen were switched to a coxib. TIME HORIZON: Lifetime. OUTCOME MEASURES: Incremental cost per quality-adjusted life-year (QALY) gained. RESULTS OF BASE-CASE ANALYSIS: Using a coxib instead of a nonselective NSAID in average-risk patients cost an incremental 275 809 dollars per year to gain 1 additional QALY. RESULTS OF SENSITIVITY ANALYSIS: The incremental cost per QALY gained decreased to 55 803 dollars when the analysis was limited to the subset of patients with a history of bleeding ulcers. The coxib strategy became dominant when the cost of coxibs was reduced by 90% of the current average wholesale price. In probabilistic sensitivity analysis, if a third-party payer was willing to pay 150 000 dollars per QALY gained, then 4.3% of average-risk patients would fall within the budget. CONCLUSIONS: The risk reduction seen with coxibs does not offset their increased costs compared with nonselective NSAIDs in the management of average-risk patients with chronic arthritis. However, coxibs may provide an acceptable incremental cost-effectiveness ratio in the subgroup of patients with a history of bleeding ulcers.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

Economic evaluation of neonatal health protection programs for cattle.

OBJECTIVE: To develop an economic tool that can be used to help cattle producers evaluate benefits of neonatal health programs. DESIGN: Computer simulation of a multiple-year spreadsheet model, using economic and production variables. SAMPLE POPULATION: Records for a university research farm beef herd. PROCEDURE: Data from the university research farm beef herd for each year from 1990 to 1995 were evaluated to determine economic benefits for the cow-calf enterprise that would result from a decrease in morbidity and mortality. A baseline economic evaluation of returns to variable costs was performed, using actual production and marketing information. Actual economic performance was contrasted with a projected simulation in which morbidity and mortality were decreased. Sensitivity analysis for the simulation model assessment of a neonatal health program was also performed. RESULTS: Mean-per-cow increase in net income for the herd during the 6-year period for morbidity and mortality reductions of 20, 40, and 60% was $7.44, $14.93, and $22.42, respectively. Sensitivity analysis revealed that net income per cow was not sensitive to errors in projections of morbidity and mortality. CLINICAL IMPLICATIONS: Identifying potential economic benefits for implementing a neonatal health plan and quantifying the costs to implement each component of the plan can be used by veterinarians and their clients when formulating a proactive strategy to provide the greatest potential for economic reward.

Animals↗
PubMed2005

Computer simulation of the last support phase of the long jump.

PURPOSE: The purpose was to examine the interacting roles played by the approach velocity, the explosive strength (represented by vertical ground reaction force [VGRF]), and the change in angular momentum about a transverse axis through the jumper's center of mass (deltaHzz) during the last support phase of the long jump, using a computer simulation technique. METHODS: A two-dimensional inverted-pendulum-plus-foot segment model was developed to simulate the last support phase. Using a reference jump derived from a jump performance reported in the literature, the effects of varying individual parameters were studied using sensitivity analyses. In each sensitivity analysis, the kinematic characteristics of the longest jumps with the deltaHzz considered and not considered when the parameter of interest was altered were noted. A sensitivity analysis examining the influence of altering both approach velocity and VGRF at the same time was also conducted. RESULTS AND CONCLUSION: The major findings were that 1) the jump distance was more sensitive to changes in approach velocity (e.g., a 10% increase yielded a 10.0% increase in jump distance) than to changes in the VGRF (e.g., a 10% increase yielded a 7.2% increase in jump distance); 2) the relatively large change in jump distance when both the approach velocity and VGRF were altered (e.g., a 10% increase in both parameters yielded a 20.4% increase in jump distance), suggesting that these two parameters are not independent factors in determining the jump distance; and 3) the jump distance was overestimated if the deltaHzz was not considered in the analysis.

Algorithms↗
PubMed2006

What determines the cost-effectiveness of diabetes screening?

AIMS/HYPOTHESIS: The cost-effectiveness of screening for diabetes is unknown but has been modelled previously. None of these models has taken account of uncertainty. We aimed to describe these uncertainties in a model where the outcome was CHD risk. SUBJECTS AND METHODS: Our model used population data from the Danish Inter99 study, and simulations were run in a theoretical population of 1,000,000 individuals. CHD risk was estimated using the UK Prospective Diabetes Study (UKPDS) risk engine, and risk reduction from published randomised clinical trials. Probabilistic sensitivity analysis was used to provide confidence intervals for modelled outputs. Uncertain parameter values were independently simulated from distributions derived from existing literature and deterministic sensitivity analysis performed using multiple model runs under different strategy choices and using extreme parameter estimates. RESULTS: In the least conservative model (low costs and multiplicative risk reduction for combined treatments), the 95% confidence interval of the incremental cost-effectiveness ratio varied from pound23,300-82,000. The major contributors to this uncertainty were treatment risk reduction model parameters: the risk reduction for hypertension treatment and UKPDS risk model intercept. Overall cost-effectiveness ratio was not sensitive to decisions about which groups to screen, nor the costs of screening or treatment. It was strongly affected by assumptions about how treatments combine to reduce risk. CONCLUSIONS/INTERPRETATION: Our model suggests that there is considerable uncertainty about whether or not screening for diabetes would be cost-effective. The most important but uncertain parameter is the effect of treatment. In addition to directly influencing current policy decisions, health care modelling can identify important unknown or uncertain parameters that may be the target of future research.

Adult↗
PubMed1990

Statistical approach to the analysis of sensitivity to CNS oxygen toxicity in rats.

Animal models are widely used for the study of CNS oxygen toxicity, but confusion still exists regarding the proper statistical approach to the analysis of the data. This paper is based on data collected from unanesthetized, free-moving rats with chronically implanted cortical electrodes for continuous EEG monitoring, exposed to 5 or 6 ATA oxygen. The index measured for CNS oxygen toxicity is the duration of the latent period preceding the appearance of well-defined electrical discharges in the EEG. At both oxygen pressures studied, the duration of the latent period is not distributed normally, and variability within the groups is not homogeneous. Transformations of the latent period data were found to enhance normality, and the speed of appearance of the discharges in the EEG, which is the reciprocal of the time, seems to be a simple, useful index for CNS oxygen toxicity in rats. Two experimental designs were compared: repeated measurements vs. single exposure. No advantage was demonstrated for the use of each rat as its own control as against the comparison between data from groups of rats. Rats can be used more than once in such research, but not more than once in a single study where individual observations are assumed to be independent, since there is some positive correlation between the first and second exposures to hyperbaric oxygen in individual rats; however, the level of sensitivity of the groups is not significantly different.

Animals↗
PubMed1997

Viridans streptococcal bacteraemia due to penicillin-resistant and penicillin-sensitive streptococci: analysis of risk factors and outcome in 60 patients from a single cancer centre before and after penicillin is used for prophylaxis.

60 patients with 60 viridans streptococcal bacteraemic episodes (42 due to penicillin-sensitive and 18 due to penicillin-resistant viridans streptococci) were analysed in a population of 12,185 admissions and 1,380 bacteraemic episodes during a 7-year period in a National Cancer Institute. The incidence of viridans streptococci among bacteraemias decreased from 11.5% in 1989 to 2.5% in 1995 after penicillin was introduced for prophylaxis of febrile neutropenia in acute leukaemia in 1993. However, the proportion of penicillin-resistant viridans streptococcal bacteraemias increased from 0 in 1989 and 1990 before any prophylaxis was given, to 12.9-16.7% after quinolones were used for prophylaxis in 1991 and 1992, and to 44.4-81.8% in 1993-1995 after penicillin was added to the quinolones. Mortality rate was higher in the subgroup of penicillin-resistant viridans streptococcal bacteraemias (p < 0.05). Statistically significant risk factors in patients with penicillin-resistant (compared with penicillin-sensitive) viridans streptococcal bacteraemia were: acute leukaemia (p < 0.03), high doses of cytarabine (p < 0.05), mucocutaneous lesions (p < 0.004), breakthrough bacteraemia during prophylaxis with ofloxacine plus penicillin (p < 0.001). Multiple logistic regression analysis showed that only acute leukaemia (OR 2.05, CI 0.85-1.85, p < 0.00452) and penicillin-resistance (OR 0.71, CI 0.103-4.887, p < 0.0209) were significant independent predictors of inferior outcome. Breakthrough bacteraemia during empiric therapy with vancomycine occurred in 5 of 116 patients treated with vancomycine, and during therapy with ampicillin plus gentamicin in 6 patients of 18 treated.

Acute Disease↗
PubMed1985

The pros and cons of modelling malaria transmission.

The question is approached through three examples. Ross's model, although very simple and formulated a priori, yielded important epidemiological insights: the existence of a threshold contact rate (vectorial capacity); the decreasing sensitivity of the endemic level to changes in the contact rate, as the latter gets larger; the return to the same equilibrium endemic level, as long as the contact rate remains the same; the progressively decreasing impact of a given reduction in the contact rate until a new equilibrium is reached. The second example is Macdonald's model, in particular his sensitivity analysis; two constraints are pointed out: the weakest point, on which to concentrate control efforts, cannot be identified automatically by the sensitivity analysis; the calculation of the expected impact of an intervention commonly assumes too much uniformity (e.g. of human of vector behaviour) and this commonly leads to exaggerated expectations. The third example is the Garki model, briefly considered in terms of its assumptions, of its behaviour, of its actual utilization (only for teaching, so far), and of the cost of its development. Looking forward, three uses of models are discussed. It is suggested that, critically used, they have a place in training, in planning control and in research. With respect to their application to planning, it is argued that the need for new data is not necessarily great, also that some rather difficult direct measurements might be substituted by indirect measurements, a point illustrated by the expected relationships, following the Garki model, between different dimensions of "intensity" of malaria.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1988

Rapid and sensitive quantitative analysis of the new antimalarial N4-[2,6-dimethoxy-4-methyl-5-[(3-trifluoromethyl)phenoxy]-8- quinolinyl]-1,4-pentanediamine in plasma by liquid chromatography and electrochemical detection.

A rapid, sensitive and simple method was developed for the quantitation of the plasma concentration of N4-[2,6-dimethoxy-4-methyl-5-[(3-trifluoromethyl)phenoxy]-8- quinolinyl]-1,4-pentanediamine, a new antimalarial active against Plasmodium vivax. N4-(5-Hexoxy-6-methoxy-4-methyl-8-quinolinyl)-1,4- pentanediamine diphosphate, a similar 8-aminoquinoline, was used as an internal standard. The method involves sample clean-up by a prepacked cyano solid-phase column followed by reversed-phase liquid chromatography and oxidative electrochemical detection at +0.95 V. The assay has been validated to 5 ng/ml of plasma and is sensitive to 1 ng/ml of plasma. The results of a pilot study assessing the relative oral bioavailability of two different salt forms of the new antimalarial in dogs show the usefulness of the method for animal and human pharmacokinetic studies.

Aminoquinolines↗
PubMed2004

Economic analysis of a transesophageal echocardiography-guided approach to cardioversion of patients with atrial fibrillation: the ACUTE economic data at eight weeks.

OBJECTIVES: The aim of this study was to compare the relative cost of a transesophageal echocardiography (TEE)-guided strategy versus conventional strategy for patients with atrial fibrillation (AF) >2 days duration undergoing electrical cardioversion over an eight-week period. BACKGROUND: The Assessment of Cardioversion Using Transesophageal Echocardiography (ACUTE) trial found no difference in embolic rates between the two approaches. However, the TEE-guided strategy had a shorter time to cardioversion and a lower rate of composite bleeding. While similar clinical efficacy was concluded, the relative cost of these two strategies has not been explored. METHODS: Two economic approaches were employed in the ACUTE trial. The first approach was based on hospital charge data from complete hospital Universal Billing Code of 1992 forms, a detailed hospital charge questionnaire, or imputation. Regression analysis was used to investigate the added cost of adverse events. The second economic approach involved the development of an independent analytic model simulating treatment and actual ACUTE outcome costs as a validation of clinically derived data. Sensitivity analysis was performed on the analytic model to investigate the potential range in cost differences between the strategies. RESULTS: A total of 833 of the 1,222 patients were enrolled from 53 U.S. sites; TEE-guided (n = 420) and conventional (n = 413). At eight-week follow-up, total mean costs did not significantly differ between the two groups, respectively (6,508 dollars vs. 6,239 dollars; difference of 269 dollars; p = 0.50). Cumulative costs were 24% higher in the conventional group, primarily due to increased incidence of bleeding and hospital costs associated with bleeding. A separate analytic model showed that treatment costs were higher for the TEE-guided strategy, but outcome costs were higher for the conventional strategy. Sensitivity analysis of the analytic model illustrated that varying the incidence and cost of major bleeding and the cost of TEE had the greatest impact on cost differences between the two groups. CONCLUSIONS: In patients with AF >2 days duration undergoing electrical cardioversion, the TEE-guided group showed little difference in patient costs compared with the conventional group. The TEE strategy had higher initial treatment costs but lower outcome-associated costs. Cumulative costs were 24% higher in the conventional group, primarily due to bleeding. The TEE-guided strategy is an economically feasible approach compared with the conventional strategy.

Aged↗
PubMed1986

Intraepidemic heterogeneity of influenza A (H3N2) viruses in 1985: antigenic analysis and sensitivity to non-specific inhibitors.

During the influenza outbreak of 1984-85 22 strains of H3N2 viruses were isolated in Finland. An intra-epidemic heterogeneity was demonstrated in an antigenic analysis by haemagglutination inhibition test with antisera produced in rats. The strains could be classified into three groups which corresponded to the following reference strains: group I: A/Hong Kong/1/84, A/Hong Kong/3/84; group II: A/Philippines/2/82; group III: A/Caen/1/84. Seven of the isolates were entirely insensitive to gamma-inhibitors of guinea-pig sera, which is in contrast to the small number of these viruses found among H3N2 strains isolated in the 1970s. The insensitive strains could not be isolated until the second or third passage through the eggs, whereas about half of the sensitive and intermediate strains were already isolated during the first passage. Conversions in reactivity with gamma-inhibitors could be detected only from an intermediate or an insensitive virus to a sensitive virus when several strains were passed serially in ovo and in MDCK cultures. The findings suggest that the gamma-inhibitor-insensitive strains corresponded well to the viruses of the human host or arose from dimorphic virus populations under an arbitrary selection of terminal dilution conditions prevailing during isolation in eggs. The insensitive strains did not differ substantially from the sensitive viruses in their ability to agglutinate erythrocytes of different laboratory animals or in their disagglutination patterns. On the other hand, propagation of viruses in MDCK cultures had an effect on these properties. The results are discussed with respect to Q phase variants and receptor binding properties.

Antigens, Viral↗
PubMed1999

Cost-effectiveness of diagnostic strategies for patients with chest pain.

BACKGROUND: Many noninvasive tests exist to determine whether patients should undergo coronary angiography. The routine use of coronary angiography without previous noninvasive testing is typically not advocated. OBJECTIVE: To determine the cost-effectiveness of diagnostic strategies for patients with chest pain. DESIGN: Cost-effectiveness analysis. DATA SOURCES: Published data. TARGET POPULATION: Patients who present with chest pain, have no history of myocardial infarction, and are able to perform an exercise stress test. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTIONS: No testing, exercise electrocardiography, exercise echocardiography, exercise single-photon emission computed tomography (SPECT), and coronary angiography alone. OUTCOME MEASURES: Quality-adjusted life expectancy, lifetime cost, and incremental cost-effectiveness. RESULTS OF BASE-CASE ANALYSIS: The incremental cost-effectiveness ratio of routine coronary angiography compared with exercise echocardiography was $36,400 per quality-adjusted life-year (QALY) saved for 55-year-old men with typical angina. For 55-year-old men with atypical angina, exercise echocardiography compared with exercise electrocardiography cost $41,900 per QALY saved. If adequate exercise echocardiography was not available, exercise SPECT cost $54,800 per QALY saved compared with exercise electrocardiography for these patients. For 55-year-old men with nonspecific chest pain, the incremental cost-effectiveness ratio of exercise electrocardiography compared with no testing was $57,700 per QALY saved. RESULTS OF SENSITIVITY ANALYSIS: On the basis of a probabilistic sensitivity analysis, there is a 75% chance that exercise echocardiography costs less than $50,900 per QALY saved for 55-year-old men with atypical angina. CONCLUSIONS: Exercise electrocardiography or exercise echocardiography resulted in reasonable cost-effectiveness ratios for patients at mild to moderate risk for coronary artery disease in terms of age, sex, and type of chest pain. Coronary angiography without previous noninvasive testing resulted in reasonable cost-effectiveness ratios for patients with a high pretest probability of coronary artery disease.

Adult↗
PubMed1976

Flow microfluorimetric analysis of sensitive and resistant leukemia L1210 following 1-beta-D-arabinofuranosylcytosine in vivo.

Two groups of BALB/c X DBA/S F1 mice with sensitive and 1-beta-D-arabinofuranosylcytosine-resistant L1210 ascites, respectively, were used to study the cytokinetic effects of a single dose of 750 mg of 1-beta-D-arabinofuranosylcytosine per kg. Sequential DNA histograms, labeling indices, and mitotic indices were obtained from each of five mice at timed intervals from 0 to 72 hr. Each histogram was obtained by flow microfluorimetry, using the DNA-specific fluorochrome, mithramycin. The histograms were then integrated for cell cycle analysis. Cytokinetic perturbations occurred in both groups, but they were greater in the sensitive population where there was a relative accumulation of cells, mainly in early S phase, at 16 hr. This was followed by a relative depletion of S-phase cells. In the resistant population, there were relative accumulation of cells in early S phase at 8 and 24 hr and in mid-S phase at 32 hr, but there was no subsequent relative depletion of S-phase cells. The labeling index was rapidly reduced in both groups but was recovered in the resistant population within 4 hr. In the sensitive population, there was a transient rise in the labeling index at 8 and 16 hr. Sensitive and resistant populations of L1210 cells were rapidly and reliably distinguished by DNA content cell cycle analysis of a single sample taken between 24 and 72 hr following a large dose of 1-beta-D-arabinofuranosylcytosine. This technique has potential clinical application in the rational design and monitoring of chemotherapy.

Animals↗