Essential carbamoyl-amino acids formed in vivo in patients with end-stage renal disease managed by continuous ambulatory peritoneal dialysis: isolation, identification, and quantitation

Drugs of various classes are prescribed for intermittent claudication. However, there is some discrepancy between medical practice and the scientific basis for drug selection. We have developed a quantitative criteria-based decision analysis to evaluate all implications of drug treatment choices for intermittent claudication. Pentoxifylline, buflomedil, naftidrofuryl and ticlopidine were the drugs selected for analysis. The evaluation criteria were 1) therapeutic efficacy, 2) safety, 3) patient acceptance and 4) cost. A review panel of experts determined the relative importance of each criterion by assigning points (or utility values) to each one. The points were 48, 20, 14 and 18, respectively, for criteria 1, 2, 3 and 4. A probability value, or numerical estimate of how well a drug meets a criterion, was assigned to each drug for each of the 4 criteria. The probability value was multiplied by the utility value to determine the score for each drug and criterion. The criteria points for each drug were added for a total score for the drug. The drug with the highest overall score was pentoxifylline, with 69 points out of an ideal score of 100. The rank order for the other drugs was buflomedil, ticlopidine and naftidrofuryl. A sensitive analysis showed that the relative ranking of the drugs remained unchanged over a series of data modifications.     

Risperidone versus haloperidol: II. Cost-effectiveness

Australia and Canada are currently the only Western nations with government guidelines for analyzing the cost-effectiveness of drugs. We used guidelines issued by the Australian Pharmaceutical Benefits Advisory Committee to construct a model for comparing the cost-effectiveness of risperidone and haloperidol over a 2-year period in patients with chronic schizophrenia. Use of clozapine was also included in the analysis as an alternative treatment given to patients who proved unresponsive to therapy with haloperidol or risperidone. Results are expressed in Australian dollars. Cost-effectiveness was determined by using decision-analytic modeling to compare clinical outcomes and costs. The analytic model contained a decision tree for each of the compared agents that tracked the distribution of patients between treatment outcome pathways (i.e., scenarios). Distributions were based on probabilities derived from our meta-analysis results reported elsewhere and from other sources. Each scenario had an associated monetary cost that included all significant direct costs (i.e., hospital costs; outpatient costs; and the cost of drugs, the services of health care professionals, and government-subsidized hostel accommodation). The cost for a given outcome was the sum of costs for all scenarios leading to that outcome. Cost-effectiveness was expressed as the total cost per favorable outcome. The definition of a favorable outcome was one in which the patient was in a response phase at the end of the 2-year period. The probability of a patient experiencing a favorable outcome at the end of 2 years was 78.9% for risperidone versus 58.9% for haloperidol. The total cost of treatment for 2 years was $15,549.00 for risperidone versus $18,332.00 for haloperidol. The expected cost per favorable outcome was $19,709.00 for risperidone and $31,104.00 for haloperidol. Risperidone was more cost-effective than haloperidol and therefore was "dominant" in pharmacoeconomic terms because it produced a higher proportion of favorable outcomes at lower cost. Sensitivity analysis showed that the difference in clinical response rate was a key determinant of cost-effectiveness.     

Quality of life of cancer patients and their spouses in palliative home care

Debates about the "ideal" timing of orthodontic treatment have focused on issues of biologic development and readiness. In this article we examine psychologic issues that should be considered in the decision to initiate orthodontics in the younger child or to wait until adolescence or later. Psychologic development during the preadolescent and adolescent stages may influence the child's motive for, understanding of, and adherence to treatment regimens. Results of a study of some personality characteristics, motives, and aesthetic values of young phase I patients are presented. Questionnaires were completed by 75 children (mean age 10.85 years, 52.1% female, 84% white) and their parents. Children's perceived reasons for treatment were consistent with their parents' reports (chi 2 = 76.08, p < .001); most were referred for crowded teeth (56%) and overbite (17.3%). Although body image and self-concept scores were within the normal range, both children and their parents expected the most improvement in self-image and oral function, with greater expectations by parents on self-image (p < .0001), oral function (p < .0001), and social life (p < .03) than children themselves. Although white and minority children were similar in their self-ratings and expectations from orthodontics, the former were more critical in their aesthetic judgments. They rated faces with crowded teeth (p < .02), overbite (p < .02), and diastema (p < .01) more negatively than did ethnic minorities. These results suggest that younger children are good candidates for Phase I orthodontics, have high self-esteem and body-image, and expect orthodontics to improve their lives. White children who have been referred for Phase I orthodontics appear to have a narrower range of aesthetic acceptability than minority children.     

Outcome and complications in patients treated with continuous ambulatory peritoneal dialysis (CAPD) at a single centre during 11 years

During the past 15 years, advances in basic science related to periodontal biology, and clinical trials on prevention and treatment of periodontal disease, have dramatically changed many treatment concepts in periodontics. The most pertinent information for orthodontic practice from these studies is summarized. Also, recent advances in orthodontics, particularly regarding bonding of attachments to artificial tooth surfaces and improved long-term stabilization of orthodontic treatment results in adults by means of bonded lingual retainers have significant implications. This article outlines how recent research information from both dental specialties may be used by orthodontists to improve treatment planning, clinical management, and retention of their adult and elderly patients in whom different malocclusions are complicated by moderate to advanced periodontal destruction.     

Early office-based vs late hospital-based nasolacrimal duct probing. A clinical decision analysis

BACKGROUND: Controversy exists regarding the treatment of infants with symptomatic nasolacrimal duct obstruction. One philosophy advocates "early" nasolacrimal duct probing, generally in the office. An alternate strategy advocates medical management until the infant is approximately 12 months old to allow for spontaneous resolution, with those with persistent nasolacrimal duct obstruction usually treated by "late" probing in the hospital with the use of general anesthesia. METHODS: We used clinical decision analysis to compare these two opposing treatment strategies. A decision tree was constructed with the usual designations for probability nodes and decision points, comparing early probing at 6 months of age in the office and late probing at 12 months of age in the hospital. The initial decision point thus addressed treatment of children who still had symptomatic nasolacrimal duct obstruction at 6 months of age. One repeated probing under same-strategy conditions was performed for patients in whom initial office probing failed. Values for probability nodes were derived from the ophthalmic literature, including a 70% rate of spontaneous resolution of nasolacrimal duct obstruction between the ages of 6 and 12 months. RESULTS: Both the early office probing strategy and the late hospital probing strategy yielded success rates greater than 99%. Based on prevailing fees, the late hospital strategy cost $2,310,000 more than the early office strategy per 10,000 patients, even though fewer procedures were performed. CONCLUSION: Early office probing and late hospital probing have similar high success rates, albeit at a higher cost for the late hospital probing strategy.     

Bayesian interim analysis of phase II cancer clinical trials

Many popular sequential phase II clinical trial designs optimize some criterion subject to constraints on the error probabilities at null and alternative values of the response rate. Such designs may forfeit optimality if one fails to conduct analyses strictly according to plan. Moreover, a decision, say, to accept the experimental therapy at one interim analysis does not necessarily imply the same degree of evidence as the same decision when made at another analysis. I propose an alternative design that bases decisions on the ability of the data to persuade either a sceptic or an enthusiast. My standard of evidence, called the persuasion probability, is based on the Bayesian posterior probability that the experimental treatment is superior to the standard. The design calls for termination at any interim analysis at which an observed persuasion probability exceeds its critical value. I investigate the standards of evidence implied by some frequentist procedures and calculate frequentist properties of persuasion-probability designs.     

Addressing Pricing: Value Bidding for Engineers and Consultants

This paper presents a unique treatment of competitive bidding theory as applied to pricing engineering services. Unlike low-bid procurement, the selection of engineers and design consultants is often based on several factors such as quality, availability, reputation, resume, and references, and these criteria may or may not include price. From preliminary interviews, the authors conclude that there is a need for a systematic method of evaluating potential job opportunities and determining fair market prices. This hybrid model, Value-Bidding, refocuses the competitive bidding model from a fee-based selection criteria to a value-based selection criteria. Value-Bidding utilizes an established marketing research methodology, conjoint analysis, to establish the probability of winning based on multiple factors. The resulting analytical model enables engineers to analyze market conditions, evaluate client priorities, systematically track competitors, and optimize proposals, while maximizing the probability of winning, maximizing profit, and optimizing price.     

The System of Objectified Judgement Analysis (SOJA). A tool in rational drug selection for formulary inclusion

Rational drug selection for formulary purposes is important. Besides rational selection criteria, other factors play a role in drug decision making, such as emotional, personal financial and even unconscious criteria. It is agreed that these factors should be excluded as much as possible in the decision making process. A model for drug decision making for formulary purposes is described, the System of Objectified Judgement Analysis (SOJA). In the SOJA method, selection criteria for a given group of drugs are prospectively defined and the extent to which each drug fulfils the requirements for each criterion is determined. Each criterion is given a relative weight, i.e. the more important a given selection criterion is considered, the higher the relative weight. Both the relative scores for each drug per selection criterion and the relative weight of each criterion are determined by a panel of experts in this field. The following selection criteria are applied in all SOJA scores: clinical efficacy, incidence and severity of adverse effects, dosage frequency, drug interactions, acquisition cost, documentation, pharmacokinetics and pharmaceutical aspects. Besides these criteria, group specific criteria are also used, such as development of resistance when a SOJA score was made for antimicrobial agents. The relative weight that is assigned to each criterion will always be a subject of discussion. Therefore, interactive software programs for use on a personal computer have been developed, in which the user of the system may enter their own personal relative weight to each selection criterion and make their own personal SOJA score. The main advantage of the SOJA method is that all nonrational selection criteria are excluded and that drug decision making is based solely on rational criteria. The use of the interactive SOJA discs makes the decision process fully transparent as it becomes clear on which criteria and weighting decisions are based. We have seen that the use of this method for drug decision making greatly aids the discussion in the formulary committee, as discussion becomes much more concrete. The SOJA method is time dependent. Documentation on most products is still increasing and the score for this criterion will therefore change continuously. New products are introduced and prices are also subject to change. To overcome the time-dependence of the SOJA method, regular updates of interactive software programs are being made, in which changes in acquisition cost, documentation or a different weighting of criteria are included, as well as newly introduced products. The possibility of changing the official acquisition cost into the actual purchasing costs for the hospital in question provides a tailor-made interactive program.     

Likelihood of malignancy in a solitary pulmonary nodule: comparison of Bayesian analysis and results of FDG-PET scan

OBJECTIVE: To compare the probability of cancer in a solitary pulmonary nodule using standard criteria with Bayesian analysis and result of 2-[F-18] fluoro-2-deoxy-D-glucose-positron emission tomographic (FDG-PET) scan. SETTING: A university hospital and a teaching Veteran Affairs Medical Center. METHODS: Retrospective analysis of 52 patients who had undergone both CT scan of the chest and a FDG-PET scan for evaluation of a solitary pulmonary nodule. FDG-PET scan was classified as abnormal or normal. Utilizing Bayesian analysis, the probability of cancer using "standard criteria" available in the literature, based on patient's age, history of previous malignancy, smoking history, size and edge of nodule, and presence or absence of calcification were calculated and compared to the probability of cancer based on an abnormal or normal FDG-PET scan. Histologic study of the nodules was the gold standard. RESULTS: The likelihood ratios for malignancy in a solitary pulmonary nodule with an abnormal FDG-PET scan was 7.11 (95% confidence interval [CI], 6.36 to 7.96), suggesting a high probability for malignancy, and 0.06 (95% CI, 0.05 to 0.07) when the PET scan was normal, suggesting a high probability for benign nodule. FDG-PET scan as a single test alone was more accurate than the standard criteria and standard criteria plus PET scan in correctly classifying nodules as malignant or benign. CONCLUSION: FDG-PET scan as a single test was a better predictor of malignancy in solitary pulmonary nodules than the standard criteria using Bayesian analysis. FDG-PET scan can be a useful adjunct test in the evaluation of solitary pulmonary nodules.     

Effects of formulation and process variables on the aggregation of freeze-dried interleukin-6 (IL-6) after lyophilization and on storage

PURPOSE: To illustrate the use of a nonparametric bootstrap method in the evaluation of uncertainty in decision models analyzing cost-effectiveness. METHODS: The authors reevaluated a previously published cost-effectiveness analysis that used a Markov model comparing initial percutaneous transluminal angioplasty with bypass surgery for femoropopliteal lesions. Each probability in the model was simulated with a first-order Monte Carlo simulation to represent sampling uncertainty. Superimposed on this, a second-order Monte Carlo simulation was performed to represent parameter uncertainty, drawing the probability values from nonparametric distributions based on published data or from primary collected data as available. After simulation of a mixed (i.e., non-identical) cohort of 30,000 patients, 3,000 bootstrap samples of 1,000 patients each were drawn and the joint distribution of mean incremental costs and mean effectiveness gained was evaluated. RESULTS: Using a bootstrap sample size of 1,000 patients, 92.7% of the joint distribution of mean incremental costs and mean effectiveness gained fell in the quadrant where angioplasty dominated bypass surgery. Another 6.9% of samples demonstrated either greater effectiveness with an incremental cost-effectiveness ratio of at most $20,000/QALY gained, or cost savings with a ratio of at least $20,000 saved/QALY lost. CONCLUSION: A nonparametric bootstrap method can be used to estimate the joint distribution of mean incremental costs and mean effectiveness gained, and the results can provide an understanding of the uncertainty in a cost-effectiveness analysis based on a decision model.     

The first 100 cases: a personal audit of orthodontic treatment assessed by the PAR (peer assessment rating) index

The first 100 consecutively started cases treated by a specialist registrar in orthodontics were examined and pre- and post-study models were scored using the peer assessment rating (PAR) index. The PAR index proved both simple and reproducible to use: 92 cases had post-treatment records available, 91 patients registered a drop in PAR score, and one patient registered an increase. Of these 92 patients, 38 (41%) were greatly improved, 43 (47%) were improved, and 11 (12%) were made worse or no different (ie they failed to achieve a 30% drop in PAR score). Of the factors examined, only the appliance type used was significantly related to PAR score change. Of the 11 cases apparently made worse, individual examination revealed that four of these represented beneficial occlusal changes but due to limited treatment goals they did not register as improved using the PAR index according to previously agreed criteria. The PAR index measures 'good tooth position' which, although very important, is not the only factor in orthodontic treatment. The use of the PAR index to detect 'good' and 'bad' orthodontic treatment is not without problems. Its use in mixed dentition and adjunctive orthodontic treatments may not always be appropriate.     

Three-way ROCs

Receiver operating characteristic (ROC) analysis traditionally has dealt with dichotomous diagnostic tasks (e.g., determining whether a disorder is present or absent). Often, however, medical problems involve distinguishing among more than two diagnostic alternatives. This article extends ROC concepts to diagnostic enterprises with three possible outcomes. For a trichotomous decision task, one can plot a ROC surface on three-dimensional coordinates; the volume under the ROC surface (VUS) equals the probability that test values will allow a decision maker to correctly sort a trio of items containing a randomly-selected member from each of three populations. Thus, the VUS summarizes global diagnostic accuracy for trichotomous tests, just as the area under a ROC curve does for a two-alternative diagnostic task. Information gain at points on the surface can be calculated just as is done for two-dimensional ROC curves, and investigators can thus compare three-way ROCs by comparing maximum information gain on each ROC surface.     

An evaluation of phase I cancer clinical trial designs

Phase I clinical trials are designed to identify an appropriate dose for experimentation in phase II and III studies. I present the results from a simulation study to evaluate the performance of nine phase I designs involving the standard design, the two-stage modified Storer's design, the two-stage Korn's design, the one-stage modified continual reassessment method (CRM) designs, and the two-stage modified CRM designs. I compare the performance of the above phase I designs in terms of the following criteria: (i) the proportion of the recommended maximum tolerated dose (MTD) at each dose level; (ii) the proportion of patients treated at each dose level; (iii) the average number of patients to complete the trial; (iv) the probability of toxicity observed; and (v) the average number of cohorts to complete the trial. In general, the one-stage modified CRM II and CRM III designs perform well compared with the other designs considered in this study. The one-stage modified CRM II and III designs require much fewer numbers of cohorts than do the two-stage modified CRM II and III designs. The one-stage modified CRM II and III designs avoid the criticisms of the original CRM by reducing the average number of cohorts and toxicity incidences, while estimating the MTD more accurately than does the standard design.     

Patient-specific predictions for clinical decision-making

There are many ways in which clinicians make decisions regarding therapy for an individual patient. Invariably, the decision is supplemented by collateral information which is obtained from clinical trials. Prospective and retrospective clinical studies take an unnecessary adversarial position but each method has its place. Parametric survival analysis can produce patient-specific predictions of an event of interest for an individual patient based on the risk factor profile of that patient, and these methods are just as applicable to prospective clinical studies as they are to retrospective clinical studies. Parametric survival analysis can estimate the distribution of time to an event, estimate the phases of hazard (instantaneous risk of the event), determine risk factors associated with the event in each of the identified phases of risk, predict the time-related probability of an event for a specific patient based on his or her risk factor profile, and by risk adjustment compare the effectiveness of different therapies.     

Bronchoscopy versus empirical therapy in HIV-infected patients with presumptive Pneumocystis carinii pneumonia. A decision analysis

The outcomes of alternative strategies for the management of pulmonary complications in patients infected with the human immunodeficiency virus (HIV) and with suspected Pneumocystis carinii pneumonia were compared using a decision analysis model. A decision tree was constructed using baseline probabilities derived from published data and expert opinion. The case scenario analyzed was that of a patient not currently receiving anti-Pneumocystis prophylaxis who presents with moderate pulmonary symptoms and fulfills the Centers for Disease Control (CDC) criteria for presumptive P. carinii pneumonia. Two strategies were compared: (1) early bronchoscopy with appropriate therapy based on the results, and (2) empiric treatment for P. carinii (trimethoprim/sulfamethoxazole or pentamidine, and steroids) with delayed bronchoscopy in those not responding to 5 days of empiric therapy. The expected 1-month survival rate (with and without quality of life adjustment) was found to be essentially the same for the two strategies using the baseline probabilities, and the decision remained a toss-up within the clinically relevant range of published probabilities for P. carinii pneumonia in patients fulfilling the CDC criteria. Because early bronchoscopy does not offer any additional survival benefits and is associated with greater costs and disutility, empiric therapy would appear to be the superior management strategy in this scenario.     

The scale bandwidth of visual search

Observers were asked to locate a target in a brief, two-scale display. Accuracy of locating the target was measured as a function of the ratio between the two scales. At each scale ratio, the probability of locating the target as a function of the number of elements is well fit by the idea that the observer accurately monitors only a "critical" number of elements. The dependence of critical number on scale ratio is well accounted for by a model that assumes that the observer's decision is based on an evenly spaced array of samples. The sample spacing is under attentional control, but is always uniform.     

Configuring childbirth education to survive in managed care

The article describes original scales for the estimation of the severity of state of patients with wounds and traumas. The scale I has been developed for using at the first level of the objective estimation of severity of the wounded's state during the medical sorting. It allows the sorting to be performed very exactly and has advantages over the analogues known in the literature. At the second level the scale II is used which is meant for the estimation of the severity of the wounded's state on admission to the hospital, while at the third level the scale III is used in the dynamics of treatment. These scales are necessary due to different qualitative and quantitative signs used during making the diagnosis and different values of the diagnostic signs for establishing the probability of lethal outcomes and complications on admission to the hospital and a day after performing a complex of resuscitation measures and intensive therapy. A distinctive feature of these scales is their polycriterial character, i.e. each code of the severity is calculated according to two criteria: probability of the development of lethal outcome and complications of the injury. The scales are based on simple symptoms and can be used under the military field conditions and in extreme situations.     

Early biopsy versus empiric treatment with delayed biopsy of non-responders in suspected HIV-associated cerebral toxoplasmosis: a decision analysis

OBJECTIVE: To construct and evaluate a decision analytic model of proposed management strategies for HIV-infected patients presenting with cerebral mass lesions, radiographically compatible with toxoplasmosis, lymphoma, or other etiologies, assuming knowledge of Toxoplasma antibody status in serum. METHODS: Using decision analysis, we evaluated two management strategies, for patients found to be either Toxoplasma-seropositive or -negative, for whom an initial choice was made for early brain biopsy (EB) or for empiric therapy with delayed biopsy (ETDB) of non-responders. The outcome to be optimized was the percentage of patients alive at 12 months. Model variables included predictive value of toxoplasmosis serology, probabilities of treatment response and death within 14-21 days conditional on correct diagnosis, probability of operative death, probabilities of non-diagnostic brain biopsy conditional both on correct diagnosis and prior treatment. RESULTS: One and two-way sensitivity analyses, by Toxoplasma serostatus, led to the following conclusions (1) for Toxoplasma-seropositive patients, ETDB gives nearly equivalent outcomes to EB of all patients; (2) for Toxoplasma-seronegative patients, although both strategies have equivalent outcomes under baseline assumptions, EB is preferred if there are even small survival advantages for early versus delayed diagnosis of lymphoma or other conditions, or if risk of death within 14-21 days of ET exceeds 10% when correct diagnosis is not toxoplasmosis. CONCLUSION: Under plausible assumptions, Toxoplasma-seronegative patients will benefit from an early biopsy strategy.     

The Goettingen "Pro-Stab" removable plate system. A retrospective cephalometric study of the effects of a new Class II treatment appliance

The new removable double-plate appliance has characteristics which provide for efficient treatment of Class II malocclusions: virtually unimpaired speaking and free breathing seem to support patient compliance. The sagittal activation is easy to change and the plates for the upper and the lower jaw can be worn separately or in combination, with and without the "Pro-Stab" rods even with different wearing hours (modular concept). Evaluation of lateral head films taken at the beginning and at the end of treatment (mean interval 1.45 years) of 40 patients provided information on therapy-induced changes, which were then compared with results of recent publications. The data obtained with the new system indicate similar results as with bite-jumping appliances and headgear-supported activators. Inhibition of the sagittal development of the upper jaw and retrusion of the upper incisor segment have been primarily responsible for the correction of Class II malocclusions. The effect as regards the sagittal position of the lower jaw has been moderate. In comparison with similar appliances, protrusion of the lower incisors was more pronounced when treated with the Goettingen Type I "Pro-Stab" removable plate system.