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PubMed1994

A simple method to calculate the influence of dose inhomogeneity and fractionation in normal tissue complication probability evaluation.

PURPOSE: Since volumetric dose distributions are available with 3-dimensional radiotherapy treatment planning they can be used in statistical evaluation of response to radiation. This report presents a method to calculate the influence of dose inhomogeneity and fractionation in normal tissue complication probability evaluation. METHODS: The mathematical expression for the calculation of normal tissue complication probability has been derived combining the Lyman model with the histogram reduction method of Kutcher et al. [14] and using the normalized total dose (NTD) instead of the total dose. RESULTS: The fitting of published tolerance data, in case of homogeneous or partial brain irradiation, has been considered. For the same total or partial volume homogeneous irradiation of the brain, curves of normal tissue complication probability have been calculated with fraction size of 1.5 Gy and of 3 Gy instead of 2 Gy, to show the influence of fraction size. The influence of dose distribution inhomogeneity and alpha/beta value has also been simulated: considering alpha/beta = 1.6 Gy or alpha/beta = 4.1 Gy for kidney clinical nephritis, the calculated curves of normal tissue complication probability are shown. CONCLUSION: Combining NTD calculations and histogram reduction techniques, normal tissue complication probability can be estimated taking into account the most relevant contributing factors, including the volume effect.

Brain↗

PubMed1996

Diagnosis of pulmonary embolism by a decision analysis-based strategy including clinical probability, D-dimer levels, and ultrasonography: a management study.

BACKGROUND: Assessment of the clinical probability of pulmonary emboli sm, plasma D-dimer measurement, and lower-limb venous compression ultrasonography have all been advocated in the workup of suspected pulmonary embolism, to minimize the requirement for pulmonary angiography in patients with nondiagnostic lung scans. However, their contribution has not been assessed prospectively. METHODS: Three hundred eight consecutive patients who came to the emergency department with suspected pulmonary embolism were managed according to a diagnostic protocol that included clinical probability assessment, lung scan, and sequential noninvasive tests: plasma D-dimer measurement by enzyme-linked immunosorbent assay (a concentration <500 microgram/L ruled out pulmonary embolism) and lower-limb B-mode venous compression ultrasonography (a positive finding was diagnostic of venous thromboembolism). Patients without pulmonary embolism according to the diagnostic workup did not receive anticoagulant treatment. The safety of this approach was assessed by a 6-month follow-up. RESULTS: of the 308 patients, 106 (34%) had a diagnostic lung scan (normal in 43 and high probability in 63). For the remaining 202 patients, noninvasive workup was diagnostic in 125 (62%). Pulmonary embolism was ruled out by a low clinical probability and a nondiagnostic scan in 48 patients and a D-dimer level less than 500 microgram/L in 53; pulmonary embolism was established by a high clinical probability and a nondiagnostic scan in seven patients and by a finding of a deep vein thrombosis on ultrasonography in 17. Therefore, only 77 of these 202 patients underwent pulmonary angiography (negative in 55; positive in 22). At 6-month follow-up (completed for 99.4% of the study population), only two of the 199 patients in whom the diagnostic protocol had ruled out pulmonary embolism (1.0% [95% confidence interval, 0.1 to 3.6]) had a thromboembolic event (pulmonary embolism, one; deep vein thrombosis, one). CONCLUSIONS: This decision analysis strategy yielded a definitive noninvasive diagnosis in 62% of patients with a nondiagnostic scan and appears to be safe.

Adolescent↗

PubMed1997

The effect of ethnic and racial population substructuring on the estimation of multi-locus fixed-bin VNTR RFLP genotype probabilities.

Four East Asian ethnic and four racial VNTR RFLP Southern California databases were used to determine the impact of population substructure on fixed-bin genotype probability estimates. Two calculations were used for population-level probabilities: Stratified sampling, which takes substructuring into account, and pooling, which ignores it. Using 1000 four-locus genotypes, the relative difference between probabilities calculated with the stratified and the pooled methods did not exceed one order of magnitude out of about 11 orders of magnitude for East-Asian racial genotypes. Pooled estimates differed from cognate ethnic values by less than one order of magnitude out of about six. These findings suggest substructuring of races by major ethnic groups does not lead to large errors. Racial genotype probability variances were on average about twice the ethnic variances. Multi-racial total population probabilities calculated by the pooled and stratified methods differed by less than one order of magnitude out of five.

Asian↗

PubMedDate not supplied

Contribution of 99mTc-MIBI scintimammography to the diagnosis of non-palpable breast lesions in relation to mammographic probability of malignancy.

The low positive predictive value of mammography results in unnecessary biopsies. We present a prospective evaluation on the contribution of 99mTc-MIBI Scintimammography (SMM) to the diagnosis of breast cancer in 41 patients with non-palpable breast lesions detected by mammography. In all cases mammographical findings were indicative of biopsy and according to the probability of malignancy they were classified into three groups: high probability (17), intermediate (15), and low (9). There were 22 malignant lesions and 19 benign. In the high probability group. MIBI-SMM changed the only false positive into true negative, and showed 2 false negatives. In the intermediate group, MIBI-SMM changed 7 of 11 false positives on mammography into true negatives, and showed 1 false negative. In the low probability group MIBISMM changed 3 of the 7 false positive into true negatives without false negatives. In the 24 patients included in the intermediate and low probability groups, 10 of the 18 false positives were changed into true negatives by MIBI-SMM at the expense of 1 false negative. The addition of SMM may to reduce up to 55% of the number of unnecessary biopsies in non-palpable breast lesions.

Adult↗

PubMed2001

Recognition memory and verbal fluency differentiate probable Alzheimer disease from subcortical ischemic vascular dementia.

BACKGROUND: Alzheimer disease (AD) and vascular dementia are among the most frequently occurring causes of dementia in the world, and their accurate differentiation is important because different pharmaceutical strategies may modify the course of each disease. OBJECTIVE: To determine which of 10 neuropsychological test scores can accurately differentiate patients with probable AD from those with subcortical ischemic vascular dementia (SIVD) for use in evidence-based clinical practice. DESIGN: Patients with suspected dementia were referred to the study by family physicians, geriatricians, and neurologists. All participants received a thorough assessment according to standard diagnostic guidelines. Diagnoses of probable AD (n = 31) and probable SIVD (n = 31) were made according to consensus criteria. The diagnosticians were blind to the results of the 10 neuropsychological test scores. RESULTS: There were no significant differences between the groups in age or Mini-Mental State Examination scores. Logistic regression analyses identified 2 neuropsychological tests that best distinguished the groups (sensitivity = 81%; specificity = 84%; positive likelihood ratio = 5.1). These were the recognition memory subtest of the Rey Auditory Verbal Learning Test and the Controlled Oral Word Association Test. The AD group performed better on the oral association test, whereas the SIVD group did better on the recognition memory test. CONCLUSION: Patients with probable AD and probable SIVD can be distinguished with a high degree of accuracy using these 2 neuropsychological tests.

Aged↗

PubMed2005

Determining joint carrier probabilities of cancer-causing genes using Markov chain Monte Carlo methods.

In genetic counseling for cancer risk, the probability of carrying a mutation of a cancer-causing gene plays an important role. Family history of various cancers is important in calculating this probability. BRCAPRO is a widely used software for calculating the probability of carrying mutations in BRCA1 and BRCA2 genes given the family history of breast and ovarian cancer in first- and second-degree relatives. BRCAPRO uses an analytical (exact) calculational procedure. Using Markov chain Monte Carlo (MCMC) methods, we extend BRCAPRO to handle, in principle, any type of cancer, family history, any number of genes and alleles that each gene may have. When the information used in this MCMC approach is the same as for BRCAPRO (two genes: BRCA1 and BRCA2; two cancers: breast and ovarian; first- and second-degree relatives only), the two approaches give essentially the same answer. Extending the model to include (1) prostate cancer, (2) two mutated alleles of BRCA2, namely, mutations in Ovarian Cancer Cluster Region (OCCR) and non-OCCR region, and (3) relatives of degree greater than second-degree, leads to different carrier probabilities. The MCMC approach is a useful tool in building a comprehensive model to give accurate estimates of carrier probabilities. Such an approach will be even more important as additional information about the genetics of various cancers becomes available.

Alleles↗

PubMed2003

Electron probability distribution in AIM and ELF basins.

The probabilities of finding a certain number of electrons enclosed in a given volume is calculated and discussed for a series of molecules. Two different methodologies to do the partition of the molecular space in separate volumes are investigated: the Atoms in the Molecules, AIM, topologic analysis of the density, and the topologic analysis of the Electron Localization Function (ELF). The formulas to calculate the probability distribution are reviewed and the way to implement them shortly explained. For a series of molecules, we present how the probability distribution complement the chemical information about the localization of the electrons in certain regions of the space. The calculations show that the probability of finding Z electrons in the AIM atomic basin associated to an atom of atomic number Z is, in general, low, even when the average number of electrons is close to Z. The probability distribution on the ELF basins associated to bonds yields new insight about the nature of the respective bond.

Journal Article↗

PubMedDate not supplied

Effect of the pretest probability of intrauterine growth retardation on the predictiveness of sonographic estimated fetal weight in detecting IUGR: a clinical application of Bayes' theorem.

Four hundred and five women with singleton pregnancies and fetal age determination by crown-rump length were classified on the basis of their prenatal clinical findings into four risk categories for intrauterine growth retardation (IUGR), defined as a neonatal weight below the 10th percentile of age-dependent birth weight distribution curve. The incidence of IUGR in these four groups were 3.5% (very low risk), 20.6% (low risk), 49.6% (intermediate risk), and 88.0% (high risk). Severe growth retardation (birth weight less than 2.5th percentile) increased from 0% to 76.0% as the incidence of IUGR increased throughout the risk groups. The effect of these pretest risks on the prediction of severe IUGR by sonographic estimated fetal weight (EFW) was evaluated. The positive predictive value of the test, as well as the probability of having a growth-retarded infant after a normal EFW was obtained were considerably higher when the pretest probability of IUGR increased. In the very low risk group, the probability of severe IUGR was negligible regardless of the EFW. When the EFW was less than 10th percentile of our age-dependent EFW curve, the probability of severe IUGR in the other risk groups was high enough to warrant fetal well-being surveillance and/or timely interruption of gestation as appropriate. However, when the pretest probability was high, the risk of severe IUGR in spite of an EFW within the 10th percentile to 90th percentile remained sufficient to require fetal well-being surveillance as well. The study shows that placing ultrasound results in the context of the pretest risk of IUGR may improve clinical decision making in pregnancies complicated by fetal growth retardation.

Bayes Theorem↗

PubMed2005

Frequency of malignancy in lesions classified as probably benign after dynamic contrast-enhanced breast MRI examination.

PURPOSE: To determine the chance of malignancy in lesions classified as "probably benign" by dynamic magnetic resonance imaging (MRI), in a heterogeneous population. MATERIALS AND METHODS: Reports from 473 patients, from March 1994 to March 2002, who underwent breast MRI were retrospectively reviewed. A total of 79 patients (17%) had lesions classified as probably benign after the MRI, which required further imaging follow-up. We evaluated subsequent MRI, mammographic reports, and clinical follow-up in these patients and established the frequency of malignancy in this group. RESULTS: MRI classified probably benign lesion were diagnosed in 79 women because of focal or diffuse mild enhancement and benign dynamic enhancement curves in the area of the mammographic abnormality, or because of the presence of microcalcifications on the mammogram, or because of incidental enhancing lesions. Two-year radiographic and/or clinical follow-up was available in 68 women. On follow-up, four women (6%) were diagnosed with cancer between 14 and 18 months after the initial MRI. CONCLUSION: Patients with a lesion assessed as probably benign by dynamic contrast enhanced MRI have a higher chance of malignancy than patients with probably benign lesions (Breast Imaging Reporting and Data System category 3, BI-RADS 3) seen on mammography. These patients should be informed of the increased risk of cancer and be given the option of biopsy or close follow-up.

Adult↗

PubMed2006

Panic reactions to terrorist attacks and probable posttraumatic stress disorder in adolescents.

A number of factors, including subjective reactions and appraisal of danger, influence one's reaction to a traumatic event. This study used telephone survey methodology to examine adolescent and parent reactions to the 2001 World Trade Center attacks 6 to 9 months after they occurred. The prevalence of probable posttraumatic stress disorder (PTSD) in adolescents was 12.6%; 26.2% met study criteria for probable subthreshold PTSD. A probable peri-event panic attack in adolescents was strongly associated with subsequent probable PTSD and probable subthreshold PTSD. This study suggests that the early identification of peri-event panic attacks following mass traumatic events may provide an important gateway to intervention in the subsequent development of PTSD. Future studies should use longitudinal designs to examine the course and pathogenic pathways for the development of panic, PTSD, and other anxiety disorders after exposure to disasters.

Adolescent↗

PubMed2003

Estimating cumulative probabilities from incomplete longitudinal binary responses with application to HIV vaccine trials.

When describing longitudinal binary response data, it may be desirable to estimate the cumulative probability of at least one positive response by some time point. For example, in phase I and II human immunodeficiency virus (HIV) vaccine trials, investigators are often interested in the probability of at least one vaccine-induced CD8+ cytotoxic T-lymphocyte (CTL) response to HIV proteins at different times over the course of the trial. In this setting, traditional estimates of the cumulative probabilities have been based on observed proportions. We show that if the missing data mechanism is ignorable, the traditional estimator of the cumulative success probabilities is biased and tends to underestimate a candidate vaccine's ability to induce CTL responses. As an alternative, we propose applying standard optimization techniques to obtain maximum likelihood estimates of the response profiles and, in turn, the cumulative probabilities of interest. Comparisons of the empirical and maximum likelihood estimates are investigated using data from simulations and HIV vaccine trials. We conclude that maximum likelihood offers a more accurate method of estimation, which is especially important in the HIV vaccine setting as cumulative CTL responses will likely be used as a key criterion for large scale efficacy trial qualification.

AIDS Vaccines↗

PubMed1999

The Effects of Framing, Reflection, Probability, and Payoff on Risk Preference in Choice Tasks.

A meta-analysis of Asian-disease-like studies is presented to identify the factors which determine risk preference. First the confoundings between probability levels, payoffs, and framing conditions are clarified in a task analysis. Then the role of framing, reflection, probability, type, and size of payoff is evaluated in a meta-analysis. It is shown that bidirectional framing effects exist for gains and for losses. Presenting outcomes as gains tends to induce risk aversion, while presenting outcomes as losses tends to induce risk seeking. Risk preference is also shown to depend on the size of the payoffs, on the probability levels, and on the type of good at stake (money/property vs human lives). In general, higher payoffs lead to increasing risk aversion. Higher probabilities lead to increasing risk aversion for gains and to increasing risk seeking for losses. These findings are confirmed by a subsequent empirical test. Shortcomings of existing formal theories, such as prospect theory, cumulative prospect theory, venture theory, and Markowitz's utility theory, are identified. It is shown that it is not probabilities or payoffs, but the framing condition, which explains most variance. These findings are interpreted as showing that no linear combination of formally relevant predictors is sufficient to capture the essence of the framing phenomenon. Copyright 1999 Academic Press.

Journal Article↗

PubMed1998

Probability of a segregating pattern in a sample of DNA sequences.

Mutations that result in segregating sites (polymorphic sites) in a sample of DNA sequences can be classified into different types. A pattern of segregating sites is an array of the numbers of various types of mutations. Using an urn model, the probability of a pattern of segregating sites can be expressed as a recurrence equation and its value can be computed sequentially. Among those that can be computed by this method are the probability of obtaining k external mutations (mutations that occur in external branches of the genealogy of a sample), the probability of obtaining k internal mutations (mutations that occur in internal branches), the probability of obtaining k singletons (segregating sites at which one of the two segregating nucleotides is present in only one sequence), and the probability of obtaining k non-singletons. Two applications of the method are discussed. One is a maximum likelihood estimation of straight theta and another is a Bayesian statistical test of the hypothesis of neutral mutations.

Bayes Theorem↗

PubMed2002

Markov model-based estimation of individual survival probability for medullary thyroid cancer patients.

UNLABELLED: The relatively benign, but occasionally rapidly fatal clinical course of medullary thyroid cancer (MTC) has raised the need for individual survival probability estimation. A retrospective study on 91 MTC clinical case histories with a mean follow-up of 6 years indicated prevalences of local, regional and distant residual tumor on primary care completion of 23%, 54% and 54%, respectively. Local, regional and distant relapses during follow-up occurred in 8%, 23% and 26% of the patients, with a cause-specific death in 26% of the cases. Prognostic factors statistically significantly influencing the cause-specific survival were selected by uni- and multivariate analysis. A Markov method-based model was developed for the estimation of individual time-dependent local, regional and distant relapse-free and cause-specific survival probability functions, with parameters numerically determined via a maximum likelihood procedure. These parameters include relative risk factors related to prognosticators, a residual or recurrent local/regional/distant tumor, and combinations of these entities. In multivariate studies, the patient s age and gender, the genetic basis of the dis-ease, lymph node involvement, the existence of a general symptom (diarrhoea) at presentation, and the dosage of external irradiation proved to be prognosticators. The cause-specific survival function of the study population indicated mean 5, 10 and 15-year survival probabilities of 69%, 62% and 58%. CONCLUSION: Survival probabilities can be predicted for extrastudy cases provided that the same laws and principles govern the clinical course of these cases and those comprising the study. For individual survival probability estimation, a Pascal program (MEDUPRED) was written and is available on the home page of the National Institute of Oncology, Budapest (www.oncol.hu).

Adult↗

PubMed2000

Relation between exercise-induced ventricular arrhythmias and myocardial perfusion abnormalities in patients with intermediate pretest probability of coronary artery disease.

The significance of exercise-induced ventricular arrhythmias (VAs) is largely dependent on the clinical characteristics of the studied population. The relation between exercise-induced VAs and myocardial perfusion abnormalities has not yet been evaluated in a homogeneous patient population with intermediate probability of coronary artery disease (CAD). We studied 302 patients (mean age 54+/-9 years, 152 men and 150 women) with intermediate pretest probability of CAD (range=0.25-0.80, mean=0.43+/-0.20) by upright bicycle exercise stress test in conjunction with technetium-99m single-photon emission tomography (SPET) imaging. Exercise-induced VAs (frequent or complex premature ventricular contractions or ventricular tachycardia) occurred in 65 patients (22%). No significant difference was found between patients with and patient without VAs regarding the pretest probability of CAD (0.45+/-0.21 vs 0.43+/-0.20). Patients with exercise-induced VAs had a higher prevalence of perfusion abnormalities (52% vs 26%, P=0.002) and ischaemic electrocardiographic changes (31% vs 16%, P<0.05) compared to patients without VAs. A higher prevalence of perfusion abnormalities in patients with VAs was observed in both men (67% vs 35%, P<0.01) and women (38% vs 16%, P<0.05). However, the positive predictive value of exercise-induced VAs for the presence of myocardial perfusion abnormalities was higher in men than in women (67% vs 38%, P<0.05). The presence of abnormal myocardial perfusion was the only independent predictor of exercise-induced VAs (OR 2.2; 95% CI, 1.2-4.2) by multivariate analysis of clinical and stress test variables. It is concluded that in patients with intermediate pretest probability of CAD, exercise-induced VAs are predictive of a higher prevalence of myocardial perfusion abnormalities in both men and women. However, the positive predictive value of exercise-induced VAs for perfusion abnormalities is higher in men. Because of the underestimation of ischaemia by electrocardiographic changes, exercise-induced VAs should be interpreted as a marker of a higher probability of CAD.

Coronary Angiography↗

PubMed2005

Derivation and validation of a Bayesian network to predict pretest probability of venous thromboembolism.

STUDY OBJECTIVE: A Bayesian network can estimate a numeric pretest probability of venous thromboembolism on the basis of values of clinical variables. We determine the accuracy with which a Bayesian network can identify patients with a low pretest probability of venous thromboembolism, defined as less than or equal to 2%. METHODS: Using commercial software, we derived a population of Bayesian networks from 25 input variables collected on 3,145 emergency department (ED) patients with suspected venous thromboembolism who underwent standardized testing, including pulmonary vascular imaging, and 90-day follow-up (11.0% of patients were venous thromboembolism positive). The best-fit Bayesian network was selected using a genetic algorithm. The selected Bayesian network was tested in a validation population of 1,423 ED patients prospectively evaluated for venous thromboembolism, including 90-day follow-up (8.0% were venous thromboembolism positive). The Bayesian network probability estimate was normalized to a score of 0% to 100%. RESULTS: Of 1,423 patients in the validation cohort, 711 (50%; 95% confidence interval [CI] 47% to 52%) had a score less than or equal to 2% that predicted a low pretest probability. Of these 711 patients, 700 (98.5%; 95% CI 97.2% to 99.2%) had no venous thromboembolism at follow-up. CONCLUSION: A Bayesian network, derived and independently validated in ED populations, identified half of the validation cohort as having a low pretest probability (< or =2%); 98.5% of these patients were correctly classified by the network.

Adult↗

PubMed2005

Confidence in polymerase chain reaction diagnosis can be improved by Bayesian estimation of post-test disease probability.

OBJECTIVE: Polymerase chain reaction (PCR) techniques allow highly sensitive detection of specific DNA for diagnosis of infectious and genetic disease, but uncertainty relating to sensitivity and contamination has frequently resulted in controversy over results. We propose a new design in which the PCR contamination rate is estimated experimentally. The sensitivity of duplicate test results, and hence the post-test disease probabilities, can be derived algebraically, but wide confidence limits around these point estimates reduce their usefulness. STUDY DESIGN AND SETTING: We have developed a Bayesian method which gives better estimates of post-test disease probability and can substantially reduce uncertainty by using the prior belief that sensitivity is not lower than 90%. RESULTS: With 100 duplicate test samples and 100 control samples, we find that the post-test disease probability for concordant results (both positive or both negative) is generally unequivocal. The post-test disease probability for discordant results (one test positive and one negative) is often sufficiently clear to allow useful interpretation of individual test results, depending on the context. CONCLUSION: Using this approach, the performance of a PCR can be evaluated experimentally allowing post-test disease probability to be estimated, giving improved confidence in test results.

Bayes Theorem↗

PubMed1994

Short-term recall for 'probably benign' mammographic lesions detected in a three yearly screening programme.

The outcome of short-term recall for the follow-up of 131 screen detected 'probably benign' non-palpable mammographic lesions is presented. Patients were selected for short-term recall after attending a dedicated assessment clinic and underwent repeat ipsilateral mammography 1 year later. Interval progression in the mammographic appearance prompted excision biopsy, whereas no change led to discharge back to the normal screening protocol. Of 35,671 asymptomatic women screened between 1988 and 1992, 1762 (5%) attended an assessment clinic. Subsequently, 131 women (7% assessed, 0.4% screened) were placed on short-term recall and were reviewed between 1989 and 1993 (age range 50-67 years). The 'probably benign' lesions were: calcifications (91 cases, 69%); circumscribed density (18 cases, 14%); parenchymal deformity/stellate density (13 cases, 10%); and asymmetric breast tissue (9 cases, 7%). 128/131 women attended for short-term recall (compliance 98%). Five from 128 were subject to excision biopsy with a yield of three invasive carcinomas and two ductal carcinomas in-situ. The positive predictive values for malignancy were: overall 'probably benign' lesions (PPV 3.9%); calcifications (PPV 3.3%); circumscribed density (PPV 0%); parenchymal deformity/stellate density (PPV 15.4%); and asymmetric breast tissue (PPV 0%). The largest carcinoma measured 15 mm and none of the tumours demonstrated vascular invasion or axillary metastases placing them in a favourable prognostic group. The results suggest that short-term recall is a reasonable management option for a small number of women with 'probably benign' calcifications. Parenchymal deformity and stellate densities should probably not be managed by this approach and require excision after initial assessment. Circumscribed densities and asymmetric breast tissue can be safely discharged following assessment.

Aged↗