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PubMed2003

Breast cancer risk assessment models: applicability to African-American women.

BACKGROUND: Mortality rates are higher among African-American women with breast cancer than they are among white women. This population subset can benefit from available risk reduction strategies. Optimal public health gains from chemoprevention strategies depend on the ability to assess accurately the risk for the individual. However, it is not known if existing breast cancer prediction models are accurate predictors of the disease among African-American women. METHODS: Literature was reviewed for breast cancer risk prediction models and their validation studies. Reported data were also reviewed regarding the strength of established breast cancer risk factors for African-American women. RESULTS: The two currently accepted breast cancer risk assessment models, the Gail Model and the Claus Model, were designed primarily to provide risk assessments for white women. Neither model has been validated in African-American women. Reported data are inconsistent regarding the prevalence and strength of risk factors included in these models. CONCLUSIONS: Efforts should be made to validate existing risk assessment models in African-American women and future research should be directed at the identification of more reliable risk assessment features.

Black or African American↗

PubMed2005

Effect of alendronate on the age-specific incidence of symptomatic osteoporotic fractures.

UNLABELLED: Analyses of data from 3658 postmenopausal women with osteoporosis enrolled in the Fracture Intervention Trial showed that alendronate is effective in reducing the risk of symptomatic osteoporotic fractures across a spectrum of ages. INTRODUCTION: Most osteoporosis studies examine the relative risk of fracture based on the entire duration of treatment. Because older patients tend to be at higher risk for osteoporosis-related fractures, this analysis examined the effect of alendronate treatment on the relative risk of fracture in terms of the age that patients attained during the study. MATERIALS AND METHODS: We studied 3658 postmenopausal women with osteoporosis 55-80 years of age at baseline enrolled in the Fracture Intervention Trial, a large randomized, double-blind, placebo-controlled study. Patients were treated with placebo or with alendronate at a daily dose of 5 mg for 2 years followed by 10 mg for an additional 1-2.5 years, and monitored for clinical fractures. Age, rather than study time, was the dynamic variable in our analysis. RESULTS: The relative risk reductions for hip, clinical spine, and wrist fractures were constant across age groups, without evidence of a decline at older ages. Specifically, alendronate reduced the risk of clinical fracture by 53% at the hip (relative risk [RR] = 0.47; 95% CI = 0.27-0.81; p < 0.01), 45% at the spine (RR = 0.55; 95% CI = 0.37-0.83; p < 0.01), and 31% at the wrist (RR = 0.69; 95% CI = 0.50-0.98; p = 0.038). In addition, alendronate produced a significant risk reduction of 40% (RR = 0.60; 95% CI = 0.47-0.77; p < 0.01) for the composite event of clinical hip, spine, and wrist fractures. As a consequence of the constant relative risk model, the absolute risk reduction with alendronate treatment increased with age because of the age-related increase in fracture risk in the placebo group. The absolute risk reduction for the composite event (hip, spine, and wrist fractures together) for alendronate treatment versus placebo was 65, 80, 111, and 161 women with fractures per 10,000 PYR for the 55 to <65, 65 to <70, 70 to <75, and 75-85 year age groups, respectively. CONCLUSIONS: These data show that alendronate is effective in reducing the risk of symptomatic osteoporotic fractures across a spectrum of ages. The effectiveness is somewhat greater in patients with femoral neck T score < or = -2.5 than in those with a T score < or = -2.0.

Age Factors↗

PubMed2004

An integrated subsurface modeling and risk assessment approach for managing the petroleum-contaminated sites.

Soil and groundwater contamination can lead to a variety of impacts and risks to the communities. Identifications of management schemes with sound environmental and socio-economic efficiencies is desired. In fact, before any decisions regarding site remediation actions can be made, three major questions may have to be answered. They include "What happened underground, and what will happen in the future under the given remediation scenarios?," "Are there specific risks on the surrounding community?" and "What remediation alternatives are suitable for the site?" In this study, an integrated subsurface modeling and risk assessment method for petroleum-contaminated site management is proposed. It incorporates multi-phase flow multi-component transport modeling and ELCR-based human health risk assessment into a general framework. The proposed method is applied to a case study within a western Canada context for identifying effective management schemes with improved environmental and socio-economic efficiencies. Given conditions at the study site, six remediation alternatives based on combinations of several technologies are recommended, with the provision of analyses for equipment/manpower requirements, system designs, operations, efficiencies, and costs. These alternatives can be categorized into two groups: hybrid ex situ and in situ remediation approaches, and integrated in situ remediation approaches. This study is a new attempt that integrates issues of subsurface-contamination simulation, risk assessment, and site remediation for a real-world problem within a general research framework. The research outputs are directly useful for the industry to gain insight of the site and to make decisions of the relevant remediation actions.

Canada↗

PubMed2001

Postoperative and late survival outcomes after major amputation: findings from the Department of Veterans Affairs National Surgical Quality Improvement Program.

BACKGROUND: A surgical risk model is used to analyze postoperative mortality and late survival for older veterans who underwent above- or below-knee amputations in 119 Veterans Affairs (VA) hospitals from 1991 to 1995. METHODS: Preoperative medical conditions and laboratory values abstracted by the VA National Surgical Quality Improvement Program were linked to subsequent hospitalization and survival through 1999. Logistic regression and proportional hazards models were used to develop risk indexes for postoperative mortality and long-term survival. RESULTS: Thirty-day postoperative mortality was 6.3% for 1909 below-knee and 13.3% for 2152 above-knee amputees. Mortality varied greatly between the lowest-highest risk index quartiles (0.8%-18.4% for below-knee amputation and 2.3%-31.1% for above-knee amputation). Surviving patients had 10,827 subsequent VA hospitalizations during a median 32-month follow-up. Survival probabilities for below- and above-knee amputees were 77% and 59% at 1 year, 57% and 39% at 3 years, and 28% and 20% at 7.5 years. The lowest quartile of survival risk had a 61% five-year survival compared with 14% for the highest-risk quartile. CONCLUSION: A generic surgical risk model can be of use in stratifying prognosis after major amputation. The heavy burden of hospital use by these patients suggests the need for better disease management for this high-risk, high-cost patient population.

Adult↗

PubMed2002

Predictive model for pain recurrence after posterior fossa surgery for trigeminal neuralgia.

BACKGROUND: Surgical exploration of the posterior fossa is the definitive treatment for trigeminal neuralgia refractory to medication, but predictors of its success in effecting long-term pain relief have not been established. OBJECTIVE: To develop a model that allows stratification of patients' risk of postoperative recurrence of pain based on pretreatment factors. METHODS: We reviewed the records of 420 consecutive patients who underwent posterior fossa exploration by one of us (C.B.W.) for the treatment of idiopathic trigeminal neuralgia. The primary outcome measure was recurrence of trigeminal pain. The predictive value of preoperative and intraoperative factors was evaluated. Multivariate analysis revealed the statistically significant predictors of pain recurrence, permitting creation of a risk model for recurrence of pain. RESULTS: After surgery, trigeminal pain had lessened in 98% of patients and completely resolved in 87%. There were no perioperative deaths. After a mean follow-up of 56.3 months, 93% of patients reported significant pain improvement and 72% continued to have no pain. The estimated likelihood of pain recurrence at 8 years was 34%. Significant predictors of eventual recurrence of pain were age younger than 53 years at the time of surgery, symptoms lasting longer than 11(1/2) years, female sex, and pain on the left side in men. These factors were weighted and incorporated into a risk model that revealed 4-year pain-free survival of 89% +/- 4% for the low-risk group, 80% +/- 4% for the moderate-risk group, and 58% +/- 6% for the high-risk group (data are mean +/- SD). CONCLUSIONS: We developed a predictive model that stratifies the risk for eventual recurrence of pain after posterior fossa exploration for trigeminal neuralgia. This information may be useful in counseling patients regarding treatment.

Disease-Free Survival↗

PubMed2004

Predicting patient-reported asthma outcomes for adults in managed care.

OBJECTIVE: To develop and evaluate a set of questionnaire-based screening tools to identify risk for 1-year adverse outcomes in adults with moderate to severe asthma. STUDY DESIGN: Prospective cohort study in 16 managed care organizations in the United States. PATIENTS AND METHODS: Patients (n = 4888) with moderate-to-severe asthma completed baseline and 1-year questionnaires (response rate, 79%). Adverse outcomes included hospitalization in the past year; emergency department (ED) visit in the past year; days of lost activity in the past month; a composite measure combining hospitalization, ED use, and lost days; and severe symptoms. Risk models were constructed for each of these 5 outcomes. Candidate predictors included baseline demographic characteristics, prior asthma healthcare use, access to care, symptoms, and treatment. Outcome variables were dichotomized, and logistic regression analysis was used to estimate the probability of 1-year outcomes. RESULTS: The patients' mean age was 45 years; 69% were female, and 83% were white. At 1-year follow-up, 9% had been hospitalized in the past year, 35% had used the ED, and 36% had reduced activity in the past month; 54% reported at least 1 of these, and 53% reported severe symptoms. Twenty-one items were retained for the 5 final risk models. Overall, the strongest predictors were comorbid illnesses and prior ED use. Model discrimination using receiver operating characteristic area ranged from 0.67 to 0.78 for predicting hospitalization, ED use, lost days, any one of these outcomes, and symptoms. CONCLUSIONS: The questionnaire-based risk models identified with good discrimination asthmatics at increased risk for a range of adverse outcomes. Risk models based on patient-reported data could be used to target individuals for intervention.

Adolescent↗

PubMed2005

Risk-adjusted predictive models of mortality after index arterial operations using a minimal data set.

BACKGROUND: Reducing the data required for a national vascular database (NVD) without compromising the statistical basis of comparative audit is an important goal. This work attempted to model outcomes (mortality and morbidity) from a small and simple subset of the NVD data items, specifically urea, sodium, potassium, haemoglobin, white cell count, age and mode of admission. METHODS: Logistic regression models of risk of adverse outcome were built from the 2001 submission to the NVD using all records that contained the complete data required by the models. These models were applied prospectively against the equivalent data from the 2002 submission to the NVD. RESULTS: As had previously been found using the P-POSSUM (Portsmouth POSSUM) approach, although elective abdominal aortic aneurysm (AAA) repair and infrainguinal bypass (IIB) operations could be described by the same model, separate models were required for carotid endarterectomy (CEA) and emergency AAA repair. For CEA there were insufficient adverse events recorded to allow prospective testing of the models. The overall mean predicted risk of death in 530 patients undergoing elective AAA repair or IIB operations was 5.6 per cent, predicting 30 deaths. There were 28 reported deaths (chi(2) = 2.75, 4 d.f., P = 0.600; no evidence of lack of fit). Similarly, accurate predictions were obtained across a range of predicted risks as well as for patients undergoing repair of ruptured AAA and for morbidity. CONCLUSION: A 'data economic' model for risk stratification of national data is feasible. The ability to use a minimal data set may facilitate the process of comparative audit within the NVD.

Aortic Aneurysm, Abdominal↗

PubMed1992

Physiologically based liver modeling and risk assessment.

Because of the inherent complexity of biological systems, there is often a choice between a number of apparently equally applicable physiologically based models to describe uptake and metabolism processes in toxicology or risk assessment. These models may fit the particular data sets of interest equally well, but may give quite different parameter estimates or predictions under different (extrapolated) conditions. Such competing models can be discriminated by a number of methods, including potential refutation by means of strategic experiments, and their ability to suitably incorporate all relevant physiological processes. For illustration, three currently used models for steady-state hepatic elimination--the venous equilibration model, the parallel tube model, and the distributed sinusoidal perfusion model--are reviewed and compared with particular reference to their application in the area of risk assessment. The ability of each of the models to describe and incorporate such physiological processes as protein binding, precursor-metabolite relations and hepatic zones of elimination, capillary recruitment, capillary heterogeneity, and intrahepatic shunting is discussed. Differences between the models in hepatic parameter estimation, extrapolation to different conditions, and interspecies scaling are discussed, and criteria for choosing one model over the others are presented. In this case, the distributed model provides the most general framework for describing physiological processes taking place in the liver, and has so far not been experimentally refuted, as have the other two models. These simpler models may, however, provide useful bounds on parameter estimates and on extrapolations and risk assessments.

Animals↗

PubMed2000

[Short-wavelength automated perimetry (SWAP) in patients with suspected glaucoma (II): correlation with a probabilistic multifactorial model of risk for developing glaucomatous damage].

PURPOSE: To evaluate the efficiency and predictability of a multifactorial probability model to assess the risk of developing glaucomatous visual field defects and to determine the correlation between retinal nerve fiber layer (RNFL) photographs and short-wavelength automated perimetry (SWAP) in a population of patients suspected of having glaucoma. METHODS: One hundred and sixty eyes belonging to 83 patients with ocular hypertension [ocular pressure figures over 21 mmHg and normal conventional automated perimetry (AP) (white-white)] were included in the study. The risk of developing glaucomatous defects was assessed by a multifactorial model that includes intraocular pressure. vertical cup-to-disk ratio, age and family background. RNFL photographs and SWAP tests were also performed. RESULTS: SWAPs were pathological in 57 cases (35.6% of the sample); 23% of the perimetries were abnormal in the low-risk group while the moderate and high risk groups showed abnormal perimetries 38% and 56% respectively. The RNFL defects at the different risk levels were consistent with the SWAP results. The multiple regression analysis of the four variables included in the model showed the relationship among the risk factors, evaluated globally, and the presence of glaucomatous damage evaluated by RNFL and SWAP (p<0.001). CONCLUSIONS: The usefulness of this probability model as predictive indicator of subsequent glaucomatous damage is based on the good correlation between the risk scale and the RNFL and SWAP assessments. These techniques evaluate structural (RNFL) and functional (SWAP) changes in early stages of the glaucomatous disease.

Adult↗

PubMed1992

A comparison of risk assessment models for term and preterm low birthweight.

BACKGROUND: Most epidemiological research dealing with the assessment of risk for low birthweight has focused on all low birthweight births. Studies that have attempted to distinguish between term and preterm low birthweights have tended to examine preterm low birthweight, since the risk of perinatal mortality and morbidity is greatest for this group of infants. METHOD: This study uses data from 25,408 singleton births in a 20-county region in North Carolina to identify and compare risk factors for term and preterm low birthweights, and also examines the usefulness of separate multivariate risk assessment systems for term and preterm low birthweights that could be used in the clinical setting. RESULTS: Risk factors that overlap as significant predictors of both types of low birthweight include race, no previous live births, smoking, weight under 100 lb, and previous preterm or low birthweight birth. Age also is a significant predictor of both types of low birthweight, but in opposite directions. Younger age is associated with reduced risk of term low birthweight and increased risk of pattern low birthweight. CONCLUSION: Comparison of all risk factors indicates that different multivariate models are needed to understand the epidemiology of preterm and term low birthweights. In terms of clinical value, a general risk assessment model that combines all low birthweight births is as effective as the separate models.

Adolescent↗

PubMed2000

Development and evaluation of models to predict death and myocardial infarction following coronary angioplasty and stenting.

Prior estimates of the risk death and myocardial infarction following percutaneous coronary intervention (PCI) may not be uniformly applicable due to recent significant changes in clinical practice. Accordingly, we studied 2,804 cases from January 1997 through February 1999, in order to develop risk models to predict death, and post-procedural myocardial infarction following PCI. Risk models were constructed using multivariate logistic regression, artificial neural networks and prognostic risk scoring systems. Composite logistic regression models and artificial neural networks performed similarly in predicting the risk of major acute complications (c-index for predicting death of 0.812 and 0.807, respectively). Risk scoring models, based on the composite logistic regression beta coefficients, performed only slightly worse (c-index death = 0.794). Risk score models appear to provide reasonable discrimination while offering the potential for simple clinical implementation in the estimation of the risk of death and myocardial infarction in interventional cardiology.

Angioplasty, Balloon, Coronary↗

PubMed1990

Correlations of acoustic tissue typing of malignant melanoma and histopathologic features as a predictor of death.

Forty-six eyes with uveal melanoma were scanned with a computerized diagnostic ultrasound system before enucleation, and light microscope sections were obtained. Tumors were characterized by ultrasonically measured dimensions and power spectrum analysis, which provided information not available in conventional A- or B-scan ultrasonography. Histopathologic features, including cell clustering pattern, cell type, pigmentation, vascularity, and necrosis, were quantified. Statistically significant correlations were found between parameters derived from the power spectrum and histologic characteristics. Patients were followed up for up to ten years with 14 deaths occurring because of metastases. Using a Cox relative risk model with histopathologic data, a risk model comprising pigmentation and cell type (P less than .0001) was obtained. Using ultrasonic characteristics, a model comprising tumor volume and scatterer concentration (P = .0062) was obtained. The results suggest that ultrasonic tissue characterization and three-dimensional biometry may provide improved in vivo prognostic indicators for uveal melanoma.

Eye Enucleation↗

PubMed1987

General relative risk regression models for epidemiologic studies.

Three parametric families of relative risk functions for the analysis of case-control data are discussed. A desirable feature for any general relative risk function is that inference based on it be independent of the coding of a binary covariate. Only one of the three families considered has this property. Additionally, when the relative risk is not multiplicative, methods of inference based on the asymptotic covariance matrix are likely to be seriously misleading unless the sample size is very large, as has been noted previously in other papers. This is illustrated by means of examples. Likelihood-based procedures should routinely be employed when nonmultiplicative relative risk functions are used for analysis of case-control data.

Humans↗

PubMed1997

An introduction to the use of physiologically based pharmacokinetic models in risk assessment.

Many extrapolation issues surface in quantitative risk assessments. The extrapolation from high-dose animal studies to low-dose human exposures is of particular concern. Physiologically based pharmacokinetic (PBPK) models are often proposed as tools to mitigate the problems of extrapolation. These models provide a representation of the disposition, metabolism, and excretion of xenobiotics that are believed to possess the potential of inducing adverse human health responses. Given a model of xenobiotic disposition that is applicable for multiple species and appropriate for nonlinearity of the xenobiotic biotransformation process, better extrapolation may be possible. Unfortunately, the true structure of these models (e.g. number of compartments, type of metabolism, etc.) is seldom known, and attributes of these models (tissue volumes, partition coefficients, etc.) are often experimentally determined and often only central measures of these quantities are reported. We describe the use of PBPK models in risk assessment, the structural and parameter uncertainty in these models, and provide a simple illustration of how these characteristics can be incorporated in a statistical analysis of PBPK models. Additional complexity in the analysis of variability in the models is also outlined. This discussion is illustrated using data from methylene chloride.

Animals↗

PubMed1995

Structural equation modeling of risk factors for the development of eating disorder symptoms in female athletes.

Risk factors for the development of eating disorder symptoms in female college athletes were studied using structural equation modeling. Three risk factors: social influence for thinness, athletic performance anxiety, and self-appraisal of athletic achievement, were selected for study. The association of these risk factors and eating disorder symptoms was hypothesized to be mediated by overconcern with body size and shape. The study sample was 98 women recruited from eight sports teams at a major university. Structural equation modeling analysis supported the hypothesized model and cross-validation of the model showed the findings to be stable. The results of this correlational study suggested that eating disorder symptoms in college athletes are significantly influenced by the interaction of sociocultural pressure for thinness, athletic performance anxiety, and negative self-appraisal of athletic achievement. If these risk factors lead to overconcern with body size and shape, then the emergence of an eating disorder is more probable.

Adolescent↗

PubMed2000

Projection of cancer risks from the Japanese atomic bomb survivors to the England and Wales population taking into account uncertainty in risk parameters.

Generalized relative risk models, with adjustments to the relative risk for time after exposure and age at exposure and incorporating a linear-quadratic dose response, were fitted to the latest (Life Span Study Report 12) Japanese atomic bomb survivor cancer mortality data using Bayesian Markov Chain Monte Carlo methods, taking account of random errors in the DS86 dose estimates. The resulting uncertainty distributions in the relative risk model parameters were used to derive uncertainties in population cancer risks for a current UK population. Following an assumed administered dose of 1 Sv, leukaemia mortality risks were estimated to be 1.93x10(-2) Sv(-1) (95% CI 1.14, 3.38), or 0.44 years of life lost Sv(-1) (95% CI 0.22, 0.94). Following an assumed administered dose of 1 Sv, solid cancer mortality risks were calculated to be 10.36x10(-2) Sv(-1) (95% CI 8.41, 12.42), or 1.38 years of life lost Sv(-1) (95% CI 1.11, 1.68). In general, solid cancer risks were very similar to those predicted by classical likelihood-based methods; however, leukaemia risks were somewhat higher, by 10-35%, than those predicted by classical likelihood-based methods. This is so in both cases, irrespective of whether or not adjustments are made in these likelihood-based fits for the effects of measurement errors, and the discrepancy for leukaemia tends to be greater at higher doses. Overall, cancer risks predicted by Bayesian Markov Chain Monte Carlo methods are similar to those derived by classical likelihood-based methods and which form the basis of established estimates of radiation-induced cancer risk.

Bayes Theorem↗

PubMed2006

Field evaluation of an avian risk assessment model.

We conducted two laboratory subacute dietary toxicity tests and one outdoor subacute dietary toxicity test to determine the effectiveness of the U.S. Environmental Protection Agency's deterministic risk assessment model for evaluating the potential of adverse effects to birds in the field. We tested technical-grade diazinon and its D.Z.N 50W (50% diazinon active ingredient wettable powder) formulation on Canada goose (Branta canadensis) goslings. Brain acetylcholinesterase activity was measured, and the feathers and skin, feet, and gastrointestinal contents were analyzed for diazinon residues. The dose-response curves showed that diazinon was significantly more toxic to goslings in the outdoor test than in the laboratory tests. The deterministic risk assessment method identified the potential for risk to birds in general, but the factors associated with extrapolating from the laboratory to the field, and from the laboratory test species to other species, resulted in the underestimation of risk to the goslings. The present study indicates that laboratory-based risk quotients should be interpreted with caution.

Acetylesterase↗

PubMed2026

Kynurenine metabolism-related gene signature for prognostic stratification in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) remains a major global health burden with high mortality rates and limited therapeutic options. The identification of reliable biomarkers for early diagnosis and prognosis prediction is urgently needed. Kynurenine metabolism, a critical pathway in immune regulation and tumor progression, has been implicated in various cancers. However, its prognostic value in HCC has not been fully elucidated. This study aimed to develop a prognostic risk model based on kynurenine metabolism-related genes (KMRGs) for HCC patients. METHODS: Transcriptomic and clinical data of HCC patients were retrieved from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) databases. A prognostic risk model was established using least absolute shrinkage and selection operator (LASSO) and Cox regression analyses. Survival analysis and functional enrichment analysis were conducted to validate the predictive performance of the model and to investigate the underlying mechanisms. ALDH8A1 was ultimately identified as a target gene based on survival analysis, and its impact on tumor cell migration was assessed using the HCC cell line. RESULTS: A prognostic model based on seven KMRGs was established. The high-risk group exhibited significantly worse overall survival compared to the low-risk group. Functional enrichment analysis in high-risk patients highlighted significant enrichment in core biological processes, including spliceosome assembly and ribonucleoprotein complex biogenesis. Furthermore, a nomogram integrating the risk score and clinical pathological features was developed, demonstrating moderate predictive performance for HCC prognosis. CONCLUSIONS: This study successfully constructed a prognostic risk model based on seven KMRGs, providing a valuable tool for predicting clinical outcomes in HCC patients. These findings highlight the potential role of kynurenine metabolism in HCC progression and offer new insights for future therapeutic strategies.

ALDH8A1↗