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PubMedDate not supplied

Assessing physicians' estimates of the probability of coronary artery disease: the influence of patient characteristics.

The authors assessed physicians' probability estimates of coronary artery disease (CAD) in 250 patients undergoing a screening exercise stress test. True likelihood of disease (prevalence) was derived from the literature. Discrimination and calibration were assessed by comparing physicians' probability estimates and prevalence using pairwise comparisons, rank correlation, and linear regression. There were differences in the discriminative abilities of the physicians based on patient characteristics. For example, the physicians had better discriminative ability for patients with typical cardiac chest pain compared with atypical chest pain. The physicians were able to predict the prevalence of CAD in broad groups of patients. However, they overestimated probabilities for patients with low prevalence of disease and underestimated probabilities for patients with high prevalence of disease. The authors conclude that physicians make consistent errors in the use of probability estimates. The quality of these estimates depends on patient characteristics such as type of chest pain and true likelihood of disease.

Angiography↗

PubMed2003

Design of Phase II cancer trials evaluating survival probabilities.

BACKGROUND: Phase II cancer studies are undertaken to assess the activity of a new drug or a new treatment regimen. Activity is sometimes defined in terms of a survival probability, a binary outcome such as one-year survival that is derived from a time-to-event variable. Phase II studies are usually designed with an interim analysis so they can be stopped if early results are disappointing. Most designs that allow for an interim look are not appropriate for monitoring survival probabilities since many patients will not have enough follow-up by the time of the interim analysis, thus necessitating an inconvenient suspension of accrual while patients are being followed. METHODS: Two-stage phase II clinical trial designs are developed for evaluating survival probabilities. These designs are compared to fixed sample designs and to existing designs developed to monitor binomial probabilities to illustrate the expected reduction in sample size or study length possible with the use of the proposed designs. RESULTS: Savings can be realized in both the duration of accrual and the total study length, with the expected savings increasing as the accrual rate decreases. Misspecifying the underlying survival distribution and the accrual rate during the planning phase can adversely influence the operating characteristics of the designs. CONCLUSION: Two-stage phase II trials for assessing survival probabilities can be designed that do not require prolonged suspension of patient accrual. These designs are more efficient than single stage designs and more practical than existing two-stage designs developed for binomial outcomes, particularly in trials with slow accrual.

Clinical Trials, Phase II as Topic↗

PubMed2001

Comparison of two methods based on cross-sectional data for correcting corpus uterine cancer incidence and probabilities.

BACKGROUND: Two methods are presented for obtaining hysterectomy prevalence corrected estimates of invasive cancer incidence rates and probabilities of the corpus uterine. METHODS: The first method involves cross-sectional hysterectomy data from the Utah Hospital Discharge Data Base and mortality data applied to life-table methods. The second involves hysterectomy prevalence estimates obtained directly from the Utah Behavior Risk Factor Surveillance System (BRFSS) survey. RESULTS: Hysterectomy prevalence estimates based on the first method are lower than those obtained from the second method through age 74, but higher in the remaining ages. Correction for hysterectomy prevalence is greatest among women ages 75-79. In this age group, the uncorrected rate is 125 (per 100,000) and the corrected rate based on the life-table method is 223 using 1995-97 data, 243 using 1992-94 data, and 228 from the survey method. The uncorrected lifetime probability of developing corpus uterine cancer is 2.6%; the corrected probability from the life-table method using 1995-97 data is 4.2%, using 1992-94 data is 4.5%; and based on prevalence data from the survey method is 4.6%. CONCLUSIONS: Both methods provide reasonable hysterectomy prevalence estimates for correcting corpus uterine cancer rates and probabilities. Because of declining trends in hysterectomy in recent decades, corrected estimates from the life-table method are less pronounced than those based on the survey method. These methods may be useful for obtaining corrected uterine cancer rates and probabilities in areas of the world that do not have sufficient years of hysterectomy data to directly compute prevalence.

Adolescent↗

PubMed1999

Elevated CSF prostaglandin E2 levels in patients with probable AD.

OBJECTIVE: To determine CSF eicosanoid concentrations and brain cyclo-oxygenase activity in AD patients and age-matched control subjects. BACKGROUND: Nonsteroidal anti-inflammatory drugs may benefit AD patients by inhibiting cyclo-oxygenases and thereby reducing prostaglandin (PG) production or oxidant stress in the CNS. METHODS: CSF eicosanoid and F2-isoprostane (IsoP) levels were determined in seven probable AD patients and seven age-matched control subjects. Cyclo-oxygenase activity was determined in microsomes prepared from the hippocampus of 10 definite AD patients and 8 age-matched control subjects. All measurements were made using gas chromatography/mass spectrometry. RESULTS: CSF concentrations of prostaglandin (PG) E2 were increased fivefold (p < 0.01) and 6-keto-PGF1alpha was decreased fourfold (p < 0.01) in probable AD patients. There was no change in total CSF eicosanoid concentration in probable AD patients. CSF F2-IsoP, a quantitative marker of lipid peroxidation in vivo, was increased in probable AD patients (p < 0.05). Cyclo-oxygenase activity in the hippocampus from definite AD patients was not different from age-matched control subjects. CONCLUSIONS: These data suggest that cyclo-oxygenase activity may not contribute significantly to CNS oxidative damage in AD. Increased CSF PGE2 concentration in probable AD patients suggest that cyclo-oxygenase inhibitors may benefit AD patients by limiting PG production.

Aged↗

PubMed2000

A model for pretest probability of lymph node metastasis from cutaneous Melanoma.

Although many statistical models have been developed to predict survival in cutaneous melanoma, few predict the end point of regional lymph node metastasis shortly after the diagnosis of melanoma. We used routine clinical and histologic data from 573 patients referred to the Duke University Melanoma Clinic, Durham, NC, during the 1980s and 1990s who underwent lymph node resections during the first year after the diagnosis of primary cutaneous melanoma. The outcome we modeled (using the logistic regression model) was the probability of lymph node metastasis. We found that tumor thickness was the variable most significantly associated with the probability of nodal metastasis, and the presence of ulceration and tumor location also were significant, but age, sex, and mitotic rate were not. When the resulting logistic model predicted that the probability of nodal metastasis was more than .6, 93 of 115 patients had nodal metastasis. When the model predicted that the probability was less than .3, just 32 of 88 patients had positive nodes. Furthermore, after the result of the node sampling was known, Cox model analysis demonstrated that the pretest probability added significant information about subsequent survival.

Biopsy↗

PubMed2003

Somnambulism due to probable interaction of valproic acid and zolpidem.

OBJECTIVE: To report a case of somnambulism due to a probable interaction between valproic acid and zolpidem in a patient with no prior personal or family history of somnambulism. CASE SUMMARY: A 47-year-old white man with a history of bipolar disorder was being maintained on citalopram 40 mg once daily and zolpidem 5 mg at bedtime. During treatment, he developed manic symptoms and was started on adjunctive valproic acid therapy. Soon after this, he developed episodes of somnambulism, which stopped when valproic acid was discontinued. On rechallenge with valproic acid, somnambulism returned. DISCUSSION: To our knowledge, this is the first report in the literature describing a probable interaction between valproic acid and zolpidem leading to somnambulism. Even though valproic acid has been associated with sleep changes, there are no published reports of somnambulism with this agent. Zolpidem has been associated with somnambulism, but our patient did not experience this when he was on zolpidem monotherapy. However, within 2 days of starting adjunctive valproic acid, sleepwalking occurred. It stopped after valproic acid was withdrawn. On rechallenge with valproic acid, sleepwalking recurred. However, when zolpidem was discontinued and valproic acid was continued, somnambulism did not occur. An assessment on the Naranjo probability scale suggests probable pharmacokinetic or pharmacodynamic interactions between the 2 medications. CONCLUSIONS: Valproic acid and zolpidem are generally safe medications that are commonly prescribed and often used together. No interactions have been previously reported with combined use of valproic acid and zolpidem. This case suggests a probable interaction between these 2 agents that can have a serious consequence, somnambulism. This could be frightening to patients and put them in danger. Recognition of such interactions that place patients at risk for potentially serious adverse events is imperative for appropriate care.

Bipolar Disorder↗

PubMed2002

Objective estimates of the probability of developing hypothyroidism following radioactive iodine treatment of thyrotoxicosis.

OBJECTIVE: Several risk factors have been shown individually to influence the outcome following radioactive iodine (RAI) therapy in the treatment of hyperthyroidism. However, no attempt has been made to determine their independent prognostic values that could be used in a regression model to provide objective estimates of the probability of developing hypothyroidism. STUDY DESIGN AND METHODS: We audited records of all hyperthyroid patients treated with first dose RAI between 1980 and 1996. Patients were aetiologically categorized into Graves' disease, solitary toxic nodule and toxic multinodular goiter. Following RAI, outcome was categorized as hypothyroidism, euthyroidism and persistent hyperthyroidism. Multiple logistic regression analysis was used to identify significant risk factors, their prognostic values and probability estimates of developing hypothyroidism in the presence of one or more of these factors. RESULTS: The cumulative incidence of hypothyroidism was 55.8% at 1 year and 86.1% at 10 years. Graves' disease (odds ratio: 4.29), presence of thyroid autoantibodies (odds ratio: 3.51), no antithyroid treatment given prior to RAI (odds ratio: 2.50), non-palpable goiter (odds ratio: 2.48) and high RAI dose (odds ratio: 1.90), were identified as significant independent risk factors. We then developed a predictive table that provides objective estimates of developing hypothyroidism. In the absence of all risk factors we can predict an 11.9% probability of developing hypothyroidism; this increases linearly to a 96.4% probability in the presence of all factors. CONCLUSIONS: These objective estimates would help in understanding the relative contributions of the known risk factors, and to predict the probability of developing hypothyroidism following RAI treatment. This would not only help patients make an informed consent for a treatment that would lead to life-long replacement therapy but may also prove useful in calculating the RAI dose that may reduce or delay the onset of developing hypothyroidism.

Adult↗

PubMed2005

Probability of fixation in a heterogeneous environment.

We investigate the probability of fixation of a new mutation arising in a metapopulation that ranges over a heterogeneous selective environment. Using simulations, we test the performance of several approximations of this probability, including a new analytical approximation based on separation of the timescales of selection and migration. We extend all approximations to multideme metapopulations with arbitrary population structure. Our simulations show that no single approximation produces accurate predictions of fixation probabilities for all cases of potential interest. At the limits of low and high migration, previously published approximations are found to be highly accurate. The new separation-of-timescales approach provides the best approximations for intermediate rates of migration among habitats, provided selection is not too intense. For nonzero migration and relatively strong selection, all approximations perform poorly. However, the probability of fixation is bounded above and below by the approximations based on low and high migration limits. Surprisingly, in our simulations with symmetric migration, heterogeneous selection in a metapopulation never decreased-and sometimes substantially increased-the probability of fixation of a new allele compared to metapopulations experiencing homogeneous selection with the same mean selection intensity.

Alleles↗

PubMed1994

Effects of high-probability requests on the social interactions of young children with severe disabilities.

High-probability requests were used to increase social interactions in 3 young boys with severe disabilities who had been identified as severely socially withdrawn. A multiple baseline design across participants was used to evaluate the effects of high-probability request intervention on (a) social initiations, (b) social responses, (c) continued interactions, and (d) performance of high- and low-probability requests. The students were observed in a second setting to examine generalization effects across peers who did not participate in the training sequence and settings. The results demonstrated that the high-probability requests increased the students' responsiveness to low-probability requests to initiate social behavior. Increases were also found in (a) unprompted initiations and extended interactions to the training peers, (b) unprompted initiations and extended interactions to peers who were not involved in the training procedure, and (c) generalized unprompted initiations and interactions in a second nontraining setting. The students maintained increased levels of initiations and interactions after all prompts were removed from both the training and nontraining settings.

Autistic Disorder↗

PubMed1972

Duration discrimination: effects of probability of stimulus presentation.

Monkeys initiated a stimulus by pressing on the center of three levers and the stimulus terminated independently of behavior 60, 80, 90, or 100 sec later. Presses on the right lever were reinforced with food following the three briefer durations, and presses on the left lever, following the 100-sec duration. Incorrect responses produced a 10-sec timeout. Probability of presenting the 100-sec duration was manipulated in the range from 0.25 to 0.75, with the probabilities of the briefer durations remaining equal and summing to one minus the probability of the 100-sec duration. Percentage of responses on either side lever was functionally related to both the probability of presenting the 100-sec stimulus and to stimulus duration. An analysis of the data based on the theory of signal detection resulted in operating characteristics that were linear when plotted on normal-normal coordinates. The percentage of responses on either lever approximated the optimal values for maximizing reinforcement probability in each condition of the experiment.

Journal Article↗

PubMed1979

Signal probability, reinforcement and signal detection.

Five pigeons were trained to detect differences in light intensity. Two stimuli, S1 and S2, differing in intensity, were arranged on the center key of a three-key chamber according to set probabilities. A peck on the center key turned on the two side keys. When S1 was presented on the center key, a peck on the left key was "correct" and when S2 was presented, a peck on the right key was "correct." Correct responses produced reinforcement and incorrect responses produced 3-second blackout. Detection performance was measured under three procedures. The first was a standard signal-detection design in which the probability of S1 was varied and the number of reinforcements obtained for correct responses to S1 was allowed to covary. In the second procedure, the probability of S1 was again varied but the distribution of reinforcements between the two choices was kept equal. In the third procedure, probability of S1 was held constant while the distribution of reinforcements was varied between the two choices. Changes in response bias were a function of variations in the relative reinforcement ratio for the choice responses and not a function of variations in the probability of stimulus presentation. Discriminability remained constant across the three procedures.

Animals↗

PubMedDate not supplied

Mapping the probability of exceeding critical thresholds for cadmium concentrations in soils in The Netherlands.

The probability of exceeding critical thresholds of Cd concentrations in the soil was mapped at a national scale. The critical thresholds in soil were based on food quality criteria for Cd in crops or in organs of cattle (Bos taurus), and were calculated by inverting a regression model for the Cd concentration in the crop, with the Cd concentration in soil, soil organic matter (SOM) content, clay content, and pH as predictors. The probability of exceeding the critical threshold for Cd in soil per node of a 500- x 500-m grid was approximated by Monte Carlo simulation, using the estimated cumulative distribution functions (cdf) of SOM, clay, pH, and Cd as input. The cdfs were estimated by simple indicator kriging with local prior means. For SOM, clay, and pH, detailed maps of soil type and land use were used to define subregions with assumed constant local means of the indicators (a priori distributions). The cdfs were sampled by Latin hypercube sampling. We accounted for correlation between the actual and critical Cd concentrations in soil by drawing Cd values from cdfs conditional on SOM and clay. The estimated probability for grassland is negligible, even in areas with high Cd concentrations in soil, and for maize (Zea mays L.) land the probability is almost everywhere smaller than 5%. For arable soils, however, these probabilities commonly are larger than 5% when sugar beet (Beta vulgaris L.) or wheat (Triticum aestivum L.) is taken as a reference crop, and locally exceed 50%.

Animals↗

PubMed1984

Ventilation-perfusion scanning and pulmonary angiography: correlation in clinical high-probability pulmonary embolism.

During a 3-year period, 173 clinically selected patients underwent pulmonary angiography to confirm or exclude acute pulmonary embolism. All patients had undergone ventilation-perfusion (V/Q) scanning (167 patients) or perfusion scanning alone (six) before angiography. Angiography was done because the results of the V/Q scanning did not satisfy the clinician's needs for certainty. The results of the V/Q and studies were compared to determine the relative accuracy of V/Q scanning in this clinical setting. Pulmonary embolism was found in seven (15%) of 47 patients with low-probability scans, 11 (32%) of 34 patients with intermediate-probability scans, 22 (39%) of 57 patients with indeterminate scans, and 23 (66%) of 35 patients with high-probability scans. In this clinically selected population, low-probability scans were more accurate in excluding pulmonary embolism than were high-probability scans in establishing that diagnosis.

Humans↗

PubMed2001

Estimation of the probability for exceeding thresholds of urine specific gravity and plasma concentration of furosemide at various intervals after intravenous administration of furosemide in horses.

OBJECTIVE: To estimate the probability of concurrently exceeding thresholds for plasma concentration of furosemide and urine specific gravity after IV administration of furosemide in horses. ANIMALS: 12 mature healthy Thoroughbred (n = 6) or Quarter Horse (6) mares. PROCEDURE: Venous blood was collected from each horse prior to and 0.25, 0.5, 0.75, 1, 2, 3, 4, 4.5, 5, and 6 hours after IV administration of 250 mg (first experiment) or 500 mg (second experiment) of furosemide. Urine was collected hourly between 1 and 6 hours after administration of furosemide at both doses. Concentrations of furosemide were determined by use of an ELISA. Concentration of furosemide and urine specific gravity was modeled as a function of time, accounting for inter- and intrahorse variabilities. On the basis of pharmacokinetic and specific gravity data, the probability of exceeding a concentration of 100 ng of furosemide/ml as a function of time was determined, using a semiparametric smooth functional averaging method. A bootstrap approach was used to assess the inherent variation in this estimated probability. RESULTS: The estimated probability of exceeding the threshold of 100 ng of furosemide/ml and urine specific gravity < 1.012 was approximately 0% between 4.0 and 5.5 hours after IV administration of 250 mg of furosemide/horse, and ranged from 0 to 1% between 4 and 5.5 hours after IV administration of 500 mg of furosemide/horse. The probability of a horse being falsely identified as in violation of regulatory concentrations was inversely associated with time. CONCLUSIONS AND CLINICAL RELEVANCE: Coupling plasma furosemide concentration with urine specific gravity testing will greatly reduce the chance that some horses are misclassified as being in violation of regulatory concentrations.

Animals↗

PubMed2001

Estimation of the probability for exceeding a threshold concentration of furosemide at various intervals after intravenous administration in horses.

OBJECTIVE: To estimate the probability for exceeding a threshold concentration of furosemide commonly used for regulatory purposes after IV administration of furosemide in horses. ANIMALS: 12 mature healthy horses (6 Thoroughbreds and 6 Quarter Horses). PROCEDURE: Venous blood was collected from each horse prior to and 0.25, 0.5, 0.75, 1, 2, 3, 4, 4.5, 5, and 6 hours after administration of 250 or 500 mg of furosemide. Concentrations of furosemide were determined, using an ELISA. Concentration of furosemide was modeled as a function of time, accounting for inter- and intrahorse variabilities. On the basis of pharmacokinetic data, the probability for exceeding a concentration of 100 ng/ml as a function of time was determined, using a semiparametric smooth functional averaging method. A bootstrap approach was used to assess inherent variation in this estimated probability. RESULTS: The estimated probability of exceeding the threshold of 100 ng of furosemide/ml ranged from 11.6% at 4 hours to 2.2% at 5.5 hours after IV administration of 250 mg of furosemide/horse and 34.2% at 4 hours to 12.3% at 5.5 hours after IV administration of 500 mg of furosemide/horse. The probability of a horse being falsely identified in violation of regulatory concentrations was inversely associated with time and positively associated with dose. CONCLUSIONS AND CLINICAL RELEVANCE: Interhorse variability with respect to pharmacokinetics of furosemide will result in misclassification of some horses as being in violation of regulatory concentrations.

Animals↗

PubMed2001

Probability of Trypanosoma cruzi transmission by Triatoma infestans (Hemiptera: Reduviidae) to the opossum Didelphis albiventris (Marsupialia: Didelphidae).

The probability of Trypanosoma cruzi transmission to opossums by independent events of predation and fecal contamination during feeding ("biting") with positive Triatoma infestans was estimated. Negative female opossums were challenged for 23 hr with 10 infected third and fourth instars of T. infestans, and tests for positivity for T. cruzi by xenodiagnosis were performed at 30, 60, and 90 days. From these data, seven probability parameters were estimated by maximum likelihood, and likelihood ratio statistics confidence intervals were calculated. Simultaneous estimation of p1 (probability that a "bite" will infect an opossum), p3 (probability that a bug that has been eaten by an opossum will infect it), and p6 (probability that the opossum will become infected if faced with an infected triatomine), resulted in p1 = 0.06, p3 = 0.075, and p6 = 0.059. On average, each opossum should be exposed to an average of 700 encounters with bugs during its life, resulting in about eight potentially infective contacts, to produce the 35% opossum prevalence found in the field.

Animals↗

PubMed1999

Probable alcohol abuse or dependence: a risk factor for intensive-care readmission in patients undergoing elective vascular and thoracic surgical procedures. Mayo Perioperative Outcomes Group.

OBJECTIVE: To determine whether alcohol abuse or dependence is a risk factor for perioperative complications, increased duration of hospital stay, and increased utilization of nursing resources in patients undergoing thoracic and vascular surgical procedures. MATERIAL AND METHODS: We conducted a prospective study of all adult patients who underwent an elective vascular or thoracic surgical procedure and who received postoperative care in an intensive-care setting. Patients were screened for alcohol abuse or dependence, and actual versus expected durations of stay were evaluated. The patients' medical records were reviewed for preoperative comorbidities and perioperative complications. Fisher's exact test and the rank sum test were used in the analyses. RESULTS: Of 321 study subjects, 290 were classified as nonalcoholic and 31 as probable alcoholic patients. Patients in the probable alcohol abuse group had a significantly increased rate of alcohol withdrawal (12.9% versus 1.7%; P = 0.006) in comparison with patients in the nonalcoholic group. Patients in the probable alcohol abuse group were readmitted to an intensive-care unit more frequently (19.4% versus 7.9%; P = 0.047) and required sedation more often (32.3% versus 13.5%; P = 0.014) than those in the nonalcoholic group. No significant differences were found between the two study groups in intensive-care unit and hospital durations of stay or in utilization of nursing resources. A dismissal diagnosis of alcoholism was recorded for only one of four patients who had a documented withdrawal episode among those categorized in the probable alcoholic group and for three of five patients with alcohol withdrawal symptoms categorized in the nonalcoholic group. CONCLUSION: Except for the occurrence of alcohol withdrawal syndrome, study patients classified in the probable alcohol abuse group did not have more medical or surgical perioperative complications than patients in the nonalcoholic group. They did have significantly more intensive-care setting readmissions. Patients with documented alcohol withdrawal episodes frequently were dismissed without a diagnosis of substance abuse or dependence.

APACHE↗

PubMed2001

Minimizing synaptic depression by control of release probability.

Transmission at the end-bulb synapse formed by auditory nerve terminals onto the soma of neurons in the avian nucleus magnocellularis is characterized by high transmitter release probability and strong synaptic depression. Activation of presynaptic GABA(B) receptors minimizes depression at this synapse and significantly enhances synaptic strength during high-frequency activity. Here we investigate synaptic mechanisms underlying this phenomenon. EPSC amplitudes evoked by 200 Hz trains increased more than twofold when release probability was reduced with Cd(2+) or baclofen. This effect was not exhibited by a transmitter depletion model of presynaptic depression, which predicts that EPSC amplitudes reach a common steady-state amplitude during high-frequency trains, despite alterations of initial release probability. However, an additional source of postsynaptic depression was sufficient to explain our findings. Aniracetam, a modulator of AMPA receptors that reduces desensitization, decreased the amount of synaptic depression during trains, indicating that desensitization occurred during trains of stimuli. However, this effect of aniracetam was absent when release probability was lowered with baclofen or Cd(2+). No effect of aniracetam on the NMDA component of the EPSC was seen, confirming a postsynaptic site of action of aniracetam. When desensitization was reduced with aniracetam, steady-state EPSC amplitudes during trains were found to converge over a wide range of release probabilities, as predicted by the depletion model. Additional evidence of AMPA receptor desensitization was provided by direct measurement of quantal amplitudes immediately after stimulus trains. Thus, presynaptic modulation by GABA(B) receptors regulates the extent of AMPA receptor desensitization and controls synaptic strength, thereby modulating the flow of information at an auditory synapse.

Animals↗