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PubMed2006

An innovative application of Bayesian disease mapping methods to patient safety research: a Canadian adverse medical event study.

Recently developed disease mapping and ecological regression methods have become important techniques in studies of disease epidemiology and in health services research. This increase in importance is partially a result of the development of Bayesian statistical methodologies that make it possible to study associations between health problems and risk factors at an aggregate (i.e. areal) level while taking into account such matters as unmeasured confounding and spatial relationships. In this paper we present a demonstration of the joint use of empirical Bayes (EB) and full Bayesian inferential techniques in a small area study of adverse medical events (also known as 'iatrogenic injury') in British Columbia, Canada. In particular, we illustrate a unified Bayesian hierarchical spatial modelling framework that enables simultaneous examinations of potential associations between adverse medical event occurrence and regional characteristics, age effects, residual variation and spatial autocorrelation. We propose an analytic strategy for complementary use of EB and FB inferential techniques for risk assessment and model selection, presenting an EB-FB combined approach that draws on the strengths of each method while minimizing inherent weaknesses. The work was motivated by the need to explore relatively efficient ways to analyse regional variations of health services outcomes and resource utilization when a considerable amount of statistical modelling and inference are required.

Adolescent↗

PubMed1994

Pharmacokinetics and dosage regimens of amikacin in intensive care unit patients.

The pharmacokinetics of amikacin have been studied in 40 intensive care unit (ICU) patients using a two-compartment model and the Bayesian estimation method implemented in the USC PC-PACK program of Jelliffe et al. The volume of the central compartment was significantly higher in these patients (0.36 l.kg-1) than in the reference population (0.20 l.kg-1). A method has been designed to compute dosage regimens in order to maintain a constant steady-state average plasma concentration of 8 mg.l-1 for repeated i.v. infusions. The regimen calculated for the 'average' ICU patient varies between 11 mg.kg-1 three times per day for the patient with normal renal function and 6 mg.kg-1 every 2 days for the anuric patient. This regimen is intended to begin amikacin therapy in an ICU patient, while the population pharmacokinetic parameters would allow the individualization of the regimen by means of the Bayesian method.

Amikacin↗

PubMedDate not supplied

Prediction of solar particle event proton doses using early dose rate measurements.

A methodology for predicting solar particle event doses using Bayesian inference is being developed. As part of this development, we have tested criteria for categorization of new solar particle events (SPE) using calculated asymptotic doses and dose rates for the 22 SPEs that occurred in 2001. In 9 out of 22 events, our criteria for categorization would have over-predicted the range of asymptotic doses in which the tested events would have fallen. In two cases, our methodology under-predicted the dose range in which the event would have fallen. In order to better predict a new event's group category and thus, to better restrict the Bayesian inference predictive model parameter space, we have reexamined our dose rate criteria for categorization of new events. We report the updating of the grouping criteria using data from the 22 SPEs of 2001, as well as five additional SPEs. Using the revised grouping criteria, we present an analysis of group categorization prediction results for the first ten SPEs of 2002.

Bayes Theorem↗

PubMed2026

Cell-type-specific genetic associations in Lewy body dementia identified using single-cell eQTL-based Mendelian randomization.

BACKGROUND: Lewy body dementia (LBD) is a complex neurodegenerative disorder marked by α-synuclein aggregation and dual impairment of cognitive and motor function.While genome-wide association studies have identified risk loci, the cellular mechanisms linking genetic variation to disease susceptibility remain largely unexplored. METHODS: We performed single-cell transcriptome-wide Mendelian randomization using brain cell-type-specific eQTLs across eight major cell types. Genetic associations were evaluated using inverse-variance weighted models, followed by Bayesian colocalization analysis. Replication was performed in independent stratified LBD cohorts based on APOE ε4 carrier status. Phenome-wide association analysis was included as a supplementary, descriptive assessment of cross-trait associations. RESULTS: Expression of ANKRD65 in excitatory neurons was significantly associated with reduced LBD risk (odds ratio = 0.65, 95 % CI: 0.52-0.81, p = 0.00013). This association passed a false discovery rate of 0.1 and showed strong evidence of colocalization (posterior probability = 0.93). Effect direction was consistent across APOE ε4+ and ε4- LBD subgroups in independent cohorts. No genome-wide significant associations were observed with non-neurological traits in the phenome-wide analysis. CONCLUSIONS: Our findings identify a genetically supported, cell-type-resolved association between ANKRD65 expression in excitatory neurons and LBD risk. This study demonstrates the value of integrating cell-resolved transcriptomic regulation with genetic inference to pinpoint functionally relevant targets in neurodegenerative diseases.

Humans↗

PubMed2005

A Bayesian evaluation of enrolling additional patients at the maximum tolerated dose in Phase I trials.

At the end of the dose escalation stage of Phase I trials, investigators occasionally enroll additional patients at the maximum tolerated dose (MTD) to further explore the tolerability of the regimen. There is no explicit statistical justification for doing so; neither are there any guidelines regarding the use of toxicity information from this additional cohort with respect to the modification of MTD if necessary. This article addresses both of these issues using a Bayesian approach to model the probability of dose limiting toxicity (DLT) at the MTD. This approach takes the sequential nature of the Phase I design into account and provides predictive and posterior distributions through which various probabilities of interest can be calculated. The results suggest that MTD is usually not well defined with a cohort of 3-6 patients in the traditional dose escalation schema. Therefore, enrolling additional patients at the MTD is recommended. Also demonstrated are different ways to use the posterior density, after the additional cohort is enrolled, to decide whether the MTD is unacceptably toxic.

Bayes Theorem↗

PubMed2024

Phthalates and sex steroid hormones across the perimenopausal period: A longitudinal analysis of the Midlife Women's Health Study.

BACKGROUND: The menopausal transition involves significant sex hormone changes. Environmental chemicals, such as urinary phthalate metabolites, are associated with sex hormone levels in cross-sectional studies. Few studies have assessed longitudinal associations between urinary phthalate metabolite concentrations and sex hormone levels during menopausal transition. METHODS: Pre- and perimenopausal women from the Midlife Women's Health Study (MWHS) (n = 751) contributed data at up to 4 annual study visits. We quantified 9 individual urinary phthalate metabolites and 5 summary measures (e.g., phthalates in plastics (∑Plastic)), using pooled annual urine samples. We measured serum estradiol, testosterone, and progesterone collected at each study visit, unrelated to menstrual cycling. Linear mixed-effects models and hierarchical Bayesian kernel machine regression analyses evaluated adjusted associations between individual and phthalate mixtures with sex steroid hormones longitudinally. RESULTS: We observed associations between increased concentrations of certain phthalate metabolites and lower testosterone and higher sub-ovulatory progesterone levels, e.g., doubling of monoethyl phthalate (MEP), monobenzyl phthalate (MBzP), di-2-ethylhexyl phthalate (∑DEHP) metabolites, ∑Plastic, and ∑Phthalates concentrations were associated with lower testosterone (e.g., for ∑DEHP: -4.51%; 95% CI: -6.72%, -2.26%). For each doubling of MEP, certain DEHP metabolites, and summary measures, we observed higher mean sub-ovulatory progesterone (e.g., ∑AA (metabolites with anti-androgenic activity): 6.88%; 95% CI: 1.94%, 12.1%). Higher levels of the overall time-varying phthalate mixture were associated with lower estradiol and higher progesterone levels, especially for 2nd year exposures. CONCLUSIONS: Phthalates were longitudinally associated with sex hormone levels during the menopausal transition. Future research should assess such associations and potential health impacts during this understudied period.

Humans↗

PubMed2006

The impact of dose on parotid salivary recovery in head and neck cancer patients treated with radiation therapy.

PURPOSE: A common side effect experienced by head and neck cancer patients after radiation therapy (RT) is impairment of the parotid glands' ability to produce saliva. Our purpose is to investigate the relationship between radiation dose and saliva changes in the 2 years after treatment. METHODS AND MATERIALS: The study population includes 142 patients treated with conformal or intensity-modulated radiotherapy. Saliva flow rates from 266 parotid glands are measured before and 1, 3, 6, 12, 18, and 24 months after treatment. Measurements are collected separately from each gland under both stimulated and unstimulated conditions. Bayesian nonlinear hierarchical models were developed and fit to the data. RESULTS: Parotids receiving higher radiation produce less saliva. The largest reduction is at 1-3 months after RT followed by gradual recovery. When mean doses are lower (e.g., <25 Gy), the model-predicted average stimulated saliva recovers to pretreatment levels at 12 months and exceeds it at 18 and 24 months. For higher doses (e.g., >30 Gy), the stimulated saliva does not return to original levels after 2 years. Without stimulation, at 24 months, the predicted saliva is 86% of pretreatment levels for 25 Gy and <31% for >40 Gy. We do not find evidence to support that the overproduction of stimulated saliva at 18 and 24 months after low dose in 1 parotid gland is the result of low saliva production from the other parotid gland. CONCLUSIONS: Saliva production is affected significantly by radiation, but with doses <25-30 Gy, recovery is substantial and returns to pretreatment levels 2 years after RT.

Adult↗

PubMed2006

Corneal-thickness spatial profile and corneal-volume distribution: tomographic indices to detect keratoconus.

PURPOSE: To evaluate whether the corneal-thickness spatial profile and corneal-volume distribution differentiate keratoconic corneas from normal corneas using new tomography parameters. SETTING: Subspecialty cornea and refractive practice, Fluminense Federal University, Rio de Janeiro, Brazil. METHODS: Forty-six eyes diagnosed with mild to moderate keratoconus and 364 normal eyes were studied by the Pentacam Comprehensive Eye Scanner. Corneal thickness at the thinnest point and the averages of the points on 22 imaginary circles centered on the thinnest point with increased diameters at 0.4 mm steps were calculated to create a corneal-thickness spatial profile. Corneal volume was calculated within diameters from 1.0 to 7.0 mm with 0.5 mm steps centered on the thinnest point to create the corneal-volume distribution. The percentage increase in thickness and the percentage increase in volume were calculated for each position of the corneal-thickness spatial profile and corneal-volume distribution from their first value. Statistical analysis was done using the Wilcoxon 2-independent-sample test to compare mean levels using S-Plus-4.0 software (MathSoft) and a normal linear model under a Bayesian frame for estimating the mean variation in thickness and volume using the BUGS 0.6 package. RESULTS: Statistically significant differences were observed between the groups (P<.05) in all positions of corneal-thickness spatial profile and corneal-volume distribution and in the percentage increase in thickness and percentage increase in volume between 3.5 mm and 7.0 mm diameters. CONCLUSIONS: Corneal-thickness spatial profile, corneal-volume distribution, percentage increase in thickness, and percentage increase in volume were different between keratoconic corneas and normal corneas and could serve as indices to diagnose keratoconus and screen refractive candidates. Further studies are necessary to evaluate whether these tomographic indices are more sensitive and specific than the classic Placido-based topography.

Cornea↗

PubMedDate not supplied

Crossmodal integration for perception and action.

The integration of information from different sensory modalities has many advantages for human observers, including increase of salience, resolution of perceptual ambiguities, and unified perception of objects and surroundings. Several behavioral, electrophysiological and neuroimaging data collected in various tasks, including localization and detection of spatial events, crossmodal perception of object properties and scene analysis are reviewed here. All the results highlight the multiple faces of crossmodal interactions and provide converging evidence that the brain takes advantages of spatial and temporal coincidence between spatial events in the crossmodal binding of spatial features gathered through different modalities. Furthermore, the elaboration of a multimodal percept appears to be based on an adaptive combination of the contribution of each modality, according to the intrinsic reliability of sensory cue, which itself depends on the task at hand and the kind of perceptual cues involved in sensory processing. Computational models based on bayesian sensory estimation provide valuable explanations of the way perceptual system could perform such crossmodal integration. Recent anatomical evidence suggest that crossmodal interactions affect early stages of sensory processing, and could be mediated through a dynamic recurrent network involving backprojections from multimodal areas as well as lateral connections that can modulate the activity of primary sensory cortices, though future behavioral and neurophysiological studies should allow a better understanding of the underlying mechanisms.

Animals↗

PubMed2006

Pulmonary fissure segmentation on CT.

A pulmonary fissure is a boundary between the lobes in the lungs. Its segmentation is of clinical interest as it facilitates the assessment of lung disease on a lobar level. This paper describes a new approach for segmenting the major fissures in both lungs on thin-section computed tomography (CT). An image transformation called "ridge map" is proposed for enhancing the appearance of fissures on CT. A curve-growing process, modeled by a Bayesian network, is described that is influenced by both the features of the ridge map and prior knowledge of the shape of the fissure. The process is implemented in an adaptive regularization framework that balances these influences and reflects the causal dependencies in the Bayesian network using an entropy measure. The method effectively alleviates the problem of inappropriate weights of regularization terms, an effect that can occur with static regularization methods. The method was applied to segment and visualize the lobes of the lungs on chest CT of 10 patients with pulmonary nodules. Only 78 out of 3286 left or right lung regions with fissures (2.4%) required manual correction. The average distance between the automatically segmented and the manually delineated "ground-truth" fissures was 1.01 mm, which was similar to the average distance of 1.03 mm between two sets of manually segmented fissures. The method has a linear-time worst-case complexity and segments the upper lung from the lower lung on a standard computer in less than 5 min.

Algorithms↗

PubMed2005

An investigation of district spatial variations of childhood diarrhoea and fever morbidity in Malawi.

Although diarrhoea and malaria are among the leading causes of child mortality and morbidity in Sub-Saharan Africa, few detailed studies have examined the patterns and determinants of these ailments in the most affected communities. In this paper, we investigate the spatial distribution of observed diarrhoea and fever prevalence in Malawi using individual data for 10,185 children from the 2000 Malawi Demographic and Health survey. We highlight inequalities in child health by mapping the residual district spatial effects using a geo-additive probit model that simultaneously controls for spatial dependence in the data and potential nonlinear effects of covariates. The residual spatial effects were modelled via a Bayesian approach. For both ailments, we were able to identify a distinct district pattern of childhood morbidity. In particular, the results suggest that children living in the capital city are less affected by fever, although this is not true for diarrhoea, where some urban agglomerations are associated with a higher childhood morbidity risk. The spatial patterns emphasize the role of remoteness as well as climatic, environmental, and geographic factors on morbidity. The fixed effects show that for diarrhoea, the risk of child morbidity appears to be lower among infants who are exclusively breastfed than among those who are mixed-fed. However, exclusive breastfeeding was not found to have a protective effect on fever. An important socio-economic factor for both diarrhoea and fever morbidity was parental education, especially maternal educational attainment. Diarrhoea and fever were both observed to show an interesting association with child's age. We were able to discern the continuous worsening of the child morbidity up to 8-12 months of age. This deterioration set in right after birth and continues, more or less linearly until 8-12 months, before beginning to decline thereafter. Independent of other factors, a separate spatial process produces district inequalities in child's health.

Breast Feeding↗

PubMed2006

Evaluation of three serological tests for diagnosis of Maedi-Visna virus infection using latent class analysis.

Maedi-Visna virus (MVV) infection in sheep is present in several European countries, including Norway. The current Norwegian surveillance and control programme for MVV infection uses three serological tests: an agar gel immunodiffusion test (AGID) and two commercially available indirect ELISAs (Institut Pourquier, P-ELISA and HYPHEN BioMed, H-ELISA). From 18 flocks with suspected or confirmed MVV infection, sera from naturally infected sheep were obtained, and sensitivity (Se) and specificity (Sp) of the three tests were estimated in absence of a perfect reference test using latent class models in a Bayesian analysis. The AGID had higher Sp (95% posterior credibility interval (PCI) [98.4; 99.9]) than either ELISA (95% PCI: P-ELISA, [95.1; 99.0]; H-ELISA, [91.4; 96.6]), but much lower Se (95% PCI: AGID, [41.4; 59.8]; P-ELISA, [92.7; 100.0]; H-ELISA, [90.9; 99.4]). Currently the P-ELISA is used for screening and positive samples are subsequently confirmed by a setup using all three tests in a serial reading. The Se and Sp of the serial interpretations with and without the H-ELISA were estimated. The results suggested that the H-ELISA could be dropped as a confirmatory test as the Se of the three test serial reading was reduced significantly without adding a significant improvement of the Sp compared to the serial reading of the P-ELISA and AGID alone. However, the perceived cost of false positives versus false negatives will influence this decision. Estimates of the predictive values for the tests and combinations suggested that the P-ELISA is a good choice of screening, but confirmatory tests are needed to achieve acceptable levels of positive predictive values.

Animals↗

PubMed2006

Dog echinococcosis in northern Spain: comparison of coproantigen and serum antibody assays with coprological exam.

A large sheep-dog population from the province of Alava (northern Spain) has been investigated in order to determine the prevalence of the cestode parasite Echinococcus granulosus. Worms were detected in 14.0% of 721 dog faecal supernatants by coproantigen ELISA, and in 9.1% of 754 dog serum samples by serum antibody ELISA. A weak but statistically significant correlation (Spearman's rho=0.103, 95% CI: 0.023-0.178) between the two immunoassay results was found. In addition, eggs of the family Taeniidae were detected in 10.3% of 726 faecal samples examined by coproparasitological (flotation and sedimentation) tests. The overall E. granulosus infection rate, based on a Bayesian latent class model that accounts for the imperfect sensitivities and specificities of all diagnostic tests used, was estimated to be 8.0% (95% credible interval: 5.4-11.4%), corroborating that sheep-dog is the dog class most vulnerable to acquiring the infection. Dog sex did not influence the prevalence of E. granulosus, independently of the diagnostic test used or the dog region of origin. No significant linear correlation was found between the coproantigen ELISA OD values and the dog age (Spearman's rho=-0.049, 95% CI: -0.234 to 0.135), suggesting that there were no differences in prevalence of E. granulosus between old and young dogs. The obtained results highlight the importance of initiating a control program based on regular treatment of the sheep-dogs with praziquantel in the province of Alava.

Age Factors↗

PubMed2006

Texture properties affecting the accuracy of surface attitude judgements.

Prior studies of the perception of surface shape and attitude from texture have focused on measuring the sensitivity of the visual system to the various geometric deformations induced by projection. Studies that examine variations in accuracy caused by spatial properties of the texture itself are fewer, and often confound multiple, potentially important properties. Here we examine the perception of surface attitude for a broad range of synthetic textures that may represent the types of structure encountered in the natural world. These stimuli allow us to isolate the respective roles of texels, spatial scale structure, discrete symmetries and regularity in the judgement of both the slant and tilt of textured surfaces. Texels, spatial scale structure and discrete symmetries were all found to play a role. Discrete rotational symmetries were found to be particularly important for accurate tilt estimation, likely mediated by skew symmetry and/or linear perspective cues. The operational range of viewing distances over which accurate attitude judgements can be made is greatly extended when texture structure is distributed over multiple scales. Small biases caused by variations in the spin of symmetric textures are observed and are consistent, at least qualitatively, with a Bayesian cue combination model previously proposed by .

Cues↗

PubMed2001

Chromatic detection and discrimination analyzed by a Bayesian classifier.

Detection and threshold-level discrimination of Gabor patches were studied under the conditions of noise masking, in an attempt to isolate 'higher-order' or nonclassical color mechanisms. Detection contours in the equiluminant plane of cone contrast space were measured by varying test chromaticity in the presence of chromatic masking noise. Three equiluminant noise directions were used, in separate experiments. In the discrimination experiment, observers had to discriminate between pairs of stimuli that were fixed at their masked threshold contrasts. A Bayesian color classifier model was used to analyze the discrimination data, with no free parameters. There was no evidence of nonclassical color mechanisms in either the detection or discrimination data.

Bayes Theorem↗

PubMed1986

The changing role of the exercise electrocardiogram as a diagnostic and prognostic test for chronic ischemic heart disease.

The exercise electrocardiogram has been the subject of intense research over the last 50 years, as both a diagnostic and prognostic method to assess patients with chronic ischemic heart disease. In 1986, the strengths and limitations of the technique to predict coronary and multivessel disease in clinical patient subsets are understood. The diagnostic accuracy of the test is improved by consideration of Bayesian theory, multivariate models and new non-ST segment criteria. Post-test coronary disease risk estimates are best reported in terms of a conditional probability, rather than statements of "positive" or "negative." The value of exercise testing in prognostic risk stratification is considerably enhanced by recent reports of long-term follow-up data in asymptomatic and symptomatic patients. Powerful prognostic information can be obtained when the clinical, electrocardiographic and physiologic data from the exercise test are used to formulate the post-test risk of a cardiac event, even in patients whose coronary anatomy is known. The changing role of the exercise electrocardiogram as a diagnostic and prognostic test is reviewed, with emphasis on the strengths and limitations of the procedure.

Angina Pectoris↗

PubMed1997

Combining single patient (N-of-1) trials to estimate population treatment effects and to evaluate individual patient responses to treatment.

When treating individual patients, physicians may face difficulties using the evidence from center-based randomized control trials (RCTs) due to limitations in these studies generalizability. Therefore, they often perform their own "informal" tests of treatment effectiveness. Single patient ("N-of-1") trials provide a structured design for more rigorous assessment of medical treatments of chronic diseases, but are applied only to the index patient. We present a hierarchical Bayesian random effects model to combine N-of-1 studies to obtain an estimate of treatment effectiveness for the population and to use this population information to aid in the evaluation of an individual patient's trial results. The model's treatment effect estimates are adjustments between the population estimate and the individual's observed results. This adjustment is based upon the within-patient and between-patient heterogeneity. We demonstrate this patient-focused method using published data from 23 N-of-1 trial results comparing amitriptyline and placebo for the treatment of fibromyalgia.

Amitriptyline↗

PubMed1997

Design, construction and evaluation of systems to predict risk in obstetrics.

We present a systematic, practical approach to developing risk prediction systems, suitable for use with large databases of medical information. An important part of this approach is a novel feature selection algorithm which uses the area under the receiver operating characteristic (ROC) curve to measure the expected discriminative power of different sets of predictor variables. We describe this algorithm and use it to select variables to predict risk of a specific adverse pregnancy outcome: failure to progress in labour. Neural network, logistic regression and hierarchical Bayesian risk prediction models are constructed, all of which achieve close to the limit of performance attainable on this prediction task. We show that better prediction performance requires more discriminative clinical information rather than improved modelling techniques. It is also shown that better diagnostic criteria in clinical records would greatly assist the development of systems to predict risk in pregnancy.

Algorithms↗