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Decision analytic approach to the management of gonorrhea contacts.

We used a combination of decision analytic and modeling techniques in constructing a model for study of the management of an asymptomatic woman presenting to a sexually transmitted disease clinic as a contact of a man with gonorrhea. Total cost (physical, emotional, and economic) is expressed in units of dysutility. Initially the probabilities and "costs" of anogenital gonorrhea, incubating syphilis, carriage of the agents of nongonococcal urethritis, and coincident pharyngeal gonorrhea are considered; complications and sequelae are then accounted for. The best strategy is to culture for Neisseria gonorrhoeae, treat immediately with tetracycline, and follow up sexual partners if the culture is positive. Dysutility values calculated for the strategies of just treating with standard regimens of tetracycline, procaine penicillin, or amoxicillin are 288, 310, and 560, respectively. Sensitivity analyses show that the most important factors in determining optimal strategy are the probabilities and costs associated with the patient's carriage of the agents of nongonococcal urethritis. In order for this decision to change, the dysutility value for nongonococcal urethritis would have to decrease to 17% of our best estimate, or the overall prevalence of nongonococcal urethritis would have to be reduced to 16% of our best estimate.

Costs and Cost Analysis

Drugs and driving: a systematic analytical approach.

To collect useful epidemiological data about drug involvement in highway safety, it is essential that sensitive and specific analytical procedures be used to establish the presence of and to determine the concentrations of drugs and metabolites in samples collected from drivers. This paper describes a comprehensive and systematic screening procedure requiring 6 mL of blood, which has been used for the analysis of samples collected from injured and fatally injured drivers. The procedure uses radioimmunoassay, gas chromatography with selective detectors, and high performance liquid chromatography. Drugs and metabolites presumptively identified are then confirmed primarily using gas chromatography--chemical ionization mass spectrometry.

Accidents, Traffic

New in vitro analytical approaches for clinical chemistry measurements in critical care.

The effective management of patients in intensive care units, operating rooms, and emergency rooms requires frequent measurement of a select group of analytes, preferably at or near the patient's bedside. Tests recognized as being essential for such management include blood gases and related variables (pH, pO2, pCO2, HCO3-, hematocrit/hemoglobin, O2 saturation), electrolytes (Na+, K+, Ca2+, Cl-), and in some cases, certain metabolites (glucose, lactate, urea, creatinine). This report describes the measurement principles, practical instrumental designs, analytical performance, and limitations of several newer electrochemical sensor-based approaches useful for in vitro determination of these species in undiluted whole-blood samples. Considerable attention is given to the most recent advances in ion-selective electrode technology as they relate to blood gas and electrolyte determinations. Similar attention is given to modern enzyme-electrode techniques, which are useful for direct measurements of metabolites in whole blood. The challenges of integrating these new analytical methods into convenient, multi-analyte, user-friendly, bedside or stat-lab instruments are also discussed.

Autoanalysis

A decision-analytic approach to postexposure rabies prophylaxis.

The risks and benefits of postexposure rabies prophylaxis were analyzed from clinical and economic perspectives. A decision-analytic model was constructed by using probability and outcome data from the literature and the state health department. Health outcomes were measured in quality-adjusted life years. In the base case (overweight adult male), treatment is optimal when the probability of animal rabidity is greater than 1 in 2000. Sensitivity analysis showed robustness in the treatment decision; however, the incremental cost-effectiveness ratio ($140,000/quality-adjusted life year) is sensitive to the rabidity probability. Treatment is optimal from the patient's perspective; however, it may not be cost-effective when the probability of rabidity is low.

Animals

A decision analytic approach to the role of visual evoked response and cerebrospinal fluid abnormalities in the management of singular spinal sclerosis.

With the use of Bayesian decision analytic techniques we assess the role of visual evoked response (VER) and cerebrospinal fluid (CSF) examinations in the investigation of patients with suspected singular spinal sclerosis. An abnormal VER increases the probability of multiple sclerosis by 50%. An associated CSF abnormality does not affect this probability. In a setting of a negative VER, CSF abnormalities increase the probability of multiple sclerosis by 27%. On currently available data, VER should therefore be the primary investigation in patients with suspected singular spinal sclerosis. If the result is abnormal myelography may be omitted. CSF examinations are only useful if VER facilities are not available.

Bayes Theorem

Analytical approach for depth dose calculations (60Co beams with fixed source-target distance).

A method is described to calculate depth dose distribution to a principal plane using analytical formulas for 60Co teletherapy units and constant source-to-target distance. The formulas were derived from experimental measurements taking into consideration the obliquity of the beam. For the purposes of dose calculation the beam was divided into primary and scattered components. A computer program incorporating the formulas was developed for an IBM 360/67 computer. Dose distributions computed and obtained from experimental measurements were in good agreement. The computer program is now in use for treatment planning, including rotational techniques.

Cobalt Radioisotopes

Radially restricted linear energy transfer for high-energy protons: a new analytical approach.

Radially restricted linear energy transfer (LET) is a basic physical parameter relevant to radiation biology and radiation protection. In this report a convenient method is presented for the analytical computation of this quantity without the need for complicated simulation. The method uses the energy-restricted LET L delta, as recently redefined in a 1993 ICRU draft document and supplements it by a relatively simple term that represents the energy of fast delta rays lost within distance r from the track core. The method provides a better fit than other models and is valid over the entire range of radial distance from track center to the maximum radial distance traveled by the most energetic secondary electrons. Lr computed by this approach differs only a few percent from the values obtained from explicit Monte Carlo simulations. The concept applies equally to heavy ions and to electrons.

Linear Energy Transfer

An analytical approach to single photon emission computed tomography with the attenuation effect.

The problem of transverse plane reconstruction from an ensemble of projections is considered in its general formulation and an analytically exact solution to the attenuated tomographic operator is proposed. Such a technique, called the regularizing iterative method (RIM), allows the introduction of a priori knowledge on the size and shape of the activity distribution and in principle on the exact attenuation distribution. The relaxation factor used is so named because it provides noise filtering for a small number of iterations. The effectiveness of RIM was studied in the single photon emission computed tomography (SPECT) problem with the aim of correcting for attenuation before quantitative study. Its application involves the use of a rotating scintillation camera connected to a mini-computer system. Various mathematical and physical phantoms were studied, and a satisfactory attenuation correction was always obtained in the final image with an improvement in the contrast and signal-to-noise ratio. Preliminary clinical studies on liver transverse sections seems to indicate an improvement in deep lesion detectability, compared with images obtained by the filtered (Ramp) back projection technique.

Models, Structural

A multilevel data-analytic approach for evaluation of relationships between daily life stressors and symptomatology: patients with irritable bowel syndrome.

Four statistical strategies were used to evaluate whether occurrence of daily stressors increases lower gastrointestinal (GI) symptoms in irritable bowel syndrome (IBS) patients. Across-subject concurrent correlations between weekly stress and symptoms were positive but casually ambiguous and obscured between- and within-subject and occasion relationships. Multiple regressions assessing (weekly and daily) relations showed that prior symptoms predicted subsequent symptoms but that prior and concurrent daily stress had no consistent effects. Idiographic correlations also showed little evidence for a relationship between stress and symptoms. Daily stress did not appear to increase GI symptoms in IBS patients on a general basis. Daily recording methodology, in conjunction with within-subject analytic strategies, is proposed as an innovative approach to examine relations between stress and physical symptomatology.

Adult

Analytical approaches to the study of monoclonal antibody stability.

The stability of two purified monoclonal antibodies, MN12 and WT31, was investigated. The monoclonal antibodies were incubated for 32 days at different pH values (ranging from 3.0 to 10.0) at 4 and 37 degrees C. Various analytical methods were used to assess changes in physicochemical properties of the proteins. The monoclonal antibodies were more susceptible to degradation at 37 degrees C than at 4 degrees C. At low pH irreversible precipitation occurred. Decomposition of the proteins was enhanced at increasing pH values in the alkaline range. This was concluded from mouse IgG-specific and antigen-specific enzyme-linked immunosorbent assays, flow cytometry, analytical gel permeation chromatography, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, isoelectric focusing, and immunoblotting. No substantial change in the apparent affinity constant of MN12 was observed, as determined by an affinity enzyme-linked immunosorbent assay. Fluorescence spectra, fluorescence polarization values, and fluorescence quenching parameters of MN12 and WT31 were not substantially affected, indicating that no major irreversible conformational changes had occurred. It was concluded that each of the techniques used has only limited value for stability assessment of monoclonal antibodies and, hence, that the application of several analytical techniques is essential to gain insight into monoclonal antibody stability.

Animals

Analytical approach to the recovery of short fluorescence lifetimes from fluorescence decay curves.

Considerable effort in instrument development has made possible detection of picosecond fluorescence lifetimes by time-correlated single-photon counting. In particular, efforts have been made to narrow markedly the instrument response function (IRF). Less attention has been paid to analytical methods, especially to problem of discretization of the convolution integral, on which the detection and quantification of short lifetimes critically depends. We show that better discretization methods can yield acceptable results for short lifetimes even with an IRF several times wider than necessary for the standard discretization based on linear approximation (LA). A general approach to discretization, also suitable for nonexponential models, is developed. The zero-time shift is explicitly included. Using simulations, we compared LA, quadratic, and cubic approximations. The latter two proved much better for detection of short lifetimes and, in that respect, they do not differ except when the zero-time shift exceeds two channels, when one can benefit from using the cubic approximation. We showed that for LA in some cases narrowing the IRF beyond FWHM = 150 ps is actually counterproductive. This is not so for quadratic and cubic approximations, which we recommend for general use.

Kinetics

A decision-analytic approach to clinical nursing.

The purpose of this study was to explore the usefulness of applying decision analysis to nursing decisions about a complex, emergent patient problem. A convenience sample of 31 nurses quantified their intuitive ideas into five mutually exclusive decision alternatives. A decision-analytic process and a preference analysis of each decision alternative were conducted. Nurses' intuitive decision alternatives were compared to the decision alternatives prescribed by the decision-analytic process. Eleven nurses (35%) demonstrated agreement between their first-ranked intuitive choice and the choice prescribed by the decision-analytic model. When the relative ranking of the vector of five treatment choices derived intuitively was compared to the relative ranking prescribed by the decision-analytic model, results showed significant disagreement between nurses' intuitive and quantitative choices.

Adult

Techniques for measuring respiratory mechanics: an analytic approach with a viscoelastic model.

A homogeneous model with stress relaxation that is described by a pure viscoelastic component was recently proposed to describe the mechanical behavior of the respiratory system during mechanical ventilation (Bates et al. J. Appl. Physiol. 67: 2276-2285, 1989). With the use of this model, analytic expressions of the pressure in response to typical volume inputs are developed, and the recently published studies relating to the influence of the ventilatory pattern on respiratory mechanics are reviewed and analyzed. The analytic expression of pressure responses to rapid airway occlusion following constant-flow inflation and to sinusoidal volume oscillations allows prediction of most of the reported results. The theoretical analysis suggests that in normal subjects the observed flow and volume dependencies of respiratory mechanics are, in fact, illustrations of the dependence of the viscoelastic resistance on inspiratory time and respiratory frequency. Thus the homogeneous viscoelastic model appears suitable to describe respiratory system mechanical behavior under mechanical ventilation.

Animals

An addition to the controversy on sunlight exposure and melanoma risk: a meta-analytical approach.

Case control studies on the association between sunlight exposure and melanoma risk show considerable differences in design; this could be responsible for the variation in study results. In an attempt to resolve the controversy between study results, the results of 25 publications on case control studies were evaluated using meta-analytical techniques. Comparison of odds ratios between subgroups of studies revealed that the range of odds ratios was far greater for hospital-based studies than for population-based studies. For the latter type of studies, the odds ratios were homogeneous and the pooled odds ratios were 1.57 (95% confidence interval [CI], 1.29-1.91) for intermittent sunlight exposure and 0.73 (95% CI, 0.60-0.89) for chronic exposure. However, among other problems, the lack of standardized measures for sunlight exposure warrants cautious interpretation of these results. It is concluded that evidence to support the intermittent sunlight theory is still far from complete.

Case-Control Studies

Managing the cancer risk in chronic ulcerative colitis. A decision-analytic approach.

Chronic ulcerative colitis is associated with a high risk of colon cancer. The most appropriate management--prophylactic proctocolectomy or medical surveillance--is, at present, unclear. Recent reports suggest that the presence of colonic dysplasia or "precancer" on endoscopic biopsy may be a reliable predictor of concurrent or future colon cancer. To assess the value of colonic dysplasia in managing colitis patients, I applied decision analytic techniques to currently available data regarding the sensitivity and specificity of colonic dysplasia in colitis patients. Such analysis shows that management based on biopsy for colonic dysplasia, rather than prophylactic proctocolectomy for all colitis patients, will maximize 5-year survival. Sensitivity analysis suggests that management is primarily determined by the sensitivity of biopsy-diagnosed dysplasia--elective prophylactic surgery would be preferred only when sensitivity of dysplasia on biopsy is less than or equal to 0.70 at 20 years, or less than or equal to 0.85 at 30 years of colitis, and changing surgical mortality and survival benefit from early diagnosis within a range established by previous studies affects management decisions only when sensitivity of dysplasia is at the lower end of its reported range.

Biopsy

The infectious risks of transfusions in the United States: a decision-analytic approach.

INTRODUCTION: The development of AIDS as a result of HIV transmission and of cirrhosis as a result of chronic non-A, non-B hepatitis are the greatest infectious risks associated with transfusion in the United States. The goal of this study is to provide explicit quantitative guidelines to determine when the risk of death from all causes associated with transfusion exceeds the risk associated with anemia. METHODS: This study uses a decision-analytic model. RESULTS: On the basis of reported transfusion complication rates and an independent worst-case calculation of the risk of AIDS and non-A, non-B hepatitis, transfusion with red blood cells should be recommended as long as each unit received reduces the patient's risk of dying from anemia by at least 1/1100. DISCUSSION: Because of the relative safety of the blood supply as a result of universal screening and donor deferral, the overestimation in practice of fatal infectious complications, and the possible underestimation of the risk of anemia, undertransfusion has the potential to be as serious a problem in the United States as is overtransfusion. Although caution should be exercised not to undertransfuse when a patient has an appreciable risk of anemia-associated death, we must be wary not to overtransfuse for temporary relief of morbidity.

Acquired Immunodeficiency Syndrome

The process of gas exchange in systemic circulation in a hyperbaric environment: an analytical approach.

A mathematical model is proposed to deal with the simultaneous transport of oxygen (O2) and carbon dioxide (CO2) in systemic capillaries and the surrounding tissue in a hyperbaric environment. The transport in the capillary region depends on molecular diffusion (radial as well as axial), the convective effect of the blood, and the saturation of haemoglobin with O2 and CO2. The corresponding equation in the tissue region describes the transport of the species due to radial and axial diffusion in the tissue and consumption of O2 in the metabolic process. The production of CO2 inside the tissue is incorporated through the respiratory quotient. The saturation of blood with O2 and CO2 have been approximated by linear functions to simulate the conditions of the hyperbaric environment. The resulting system of governing equations with the physiologically relevant boundary conditions is solved analytically. The concentration of O2 is shown to decrease from the core of the capillary to the tissue periphery, whereas the concentration of CO2 increases. It is shown that very little of the CO2 is transported radially. The location of the vulnerable point from the point of view of CO2 accumulation is found to be the corner (x = R2, z = L) situated at the periphery of the tissue near the venous end of the capillary. The accumulation of O2 and CO2 in the tissue is discussed in terms of various dimensionless parameters. It is found that the accumulation of CO2 increases whereas that of O2 decreases in the hyperbaric environment. Finally, it is surmised that one of the major causes of discomfort among divers could be excessive accumulation of CO2 in the tissue.

Blood Circulation

Decision making in nosocomial pneumonia. An analytic approach to the interpretation of quantitative bronchoscopic cultures.

Quantitative cultures of specimens obtained at fiberoptic bronchoscopy have been used to diagnose nosocomial pneumonia in research settings, but their clinical role remains controversial. We reviewed the literature comparing these culture techniques with other accepted methods to diagnose pneumonia in mechanically ventilated patients and extracted data to describe the receiver operator characteristics (ROC) of quantitative cultures of protected specimen brush (PSB) and bronchoalveolar lavage (BAL) samples. Analysis of ROCs reveals that these tests have a discriminating power comparable or superior to that of many widely accepted routinely used tests. Current data do not suggest that either culture technique offers an advantage over the other. Since benefits of antibiotic therapy of pneumonia and risks of treatment of noninfected critically ill patients are not well quantified, universally applicable recommendations for appropriate values to define an abnormal test result cannot logically be made. Multiple decision analytic tools show that values lower than those previously recommended are more appropriate in patients suspected of having pneumonia unless the risk of antibiotic therapy is judged to be extreme. On the basis of these findings, we suggest guidelines for clinicians' interpretation of PSB and BAL quantitative culture results.

Bacteria