Improving outcomes and reducing cost: the role of predictive modeling.
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Analysis of Variance↗
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Elective induction versus spontaneous labor: a case-control analysis of safety and efficacy.
OBJECTIVE: To investigate the incidence, efficacy, and safety of elective induction in a community teaching hospital over 1 year. METHODS: This is a retrospective case-control study of rate, safety, and efficacy of all term inductions with vertex presentations judged to be elective by chart analysis. Cases were matched one for one for age, parity, and pay status with controls in spontaneous labor. The elective induction women were compared with those in spontaneous labor using chi2 Student t test, and Fisher exact test. Potential risk factors for cesarean delivery and neonatal intensive care unit (NICU) admission were then selected and subjected to bivariate analysis. Stepwise logistic regression was applied to control for confounding and to select which risk factors were important for those end points. RESULTS: There were 461 case-control pairs. The elective induction rate was 12.3%. Cesarean delivery was increased by elective induction in bivariate analysis (odds ratio [OR]=1.81, confidence interval [CI]=1.07, 3.08; power=.60). The cesarean delivery rate was 8.7% (control 5.0%). In a multiple regression model of potential risk factors for cesarean delivery, nulliparity (OR=6.14, CI=2.90, 13.04), cervical priming (OR=3.06, CI=1.46, 6.40), oxytocin usage (OR=2.82, CI=1.03, 7.75), gestational age at least 287 days (OR=2.51, CI=1.38, 4.58), and birth weight at least 3800 g (OR=2.29, CI=1.27, 4.13) were significant, but elective induction and epidural anesthesia were not. Elective induction did not significantly increase the rate of NICU admission (4.6% versus control 3.9%). In a multiple regression model of potential factors predicting NICU admission, only a 5-minute Apgar score of at most 8 was significant (OR = 12.34, CI=6.01, 25.3). CONCLUSION: Elective induction is commonly practiced, safe, and efficacious. Cesarean delivery is increased significantly by nulliparity and/or an unfavorable cervix, among other factors, but not by elective induction itself.
Adult↗
Anthelmintic resistance and the control of ovine ostertagiasis: a drug action model for genetic selection.
A site-specific genetic prediction model is presented, which examines the influences of different anthelmintic treatment regimens on selecting for drug resistance within a sheep management system. The model exploits the power of modern microcomputers to integrate factors such as parasite strain, geographic location, management practice and genetic fitness to identify effective control regimens which do not lead to resistant Ostertagia circumcincta strains over a 30-year horizon. The potential use of the model as a farm level management-support tool is discussed.
Animals↗
Resistance to sexual aggression: personality, attitudinal, and situational factors.
This study's purpose was to assess resistance to sexual aggression, from kissing/fondling to intercourse; to test the relative efficacy of three theoretical models (Victim Precipitation, Social Control, and Situational Blame) for predicting resistance to acquaintance rape. Seventy-five percent of the 206 university students reported vicitimization. Average time since victimization was 2.03 years. Sixty-eight percent of victims successfully resisted their most severe victimization attempt. Four situational factors predicted resistance: isolation of incident site, previous victim-offender relationship, previous victim-offender sexual intimacy, and clarity of victim nonconsent. Two personality variables, the California Personality Inventory scales of dominance and social presence, distinguished successful from unsuccessful resisters. Attitudinal measures were not statistically significant.
Adolescent↗
The basic helix-loop-helix domain of the E47 transcription factor requires other protein regions for full DNA binding activity.
Most transcription factors are believed to be composed of independently functioning modules [A. D. Frankel and P. S. Kim (1991) Cell 65, 717-719]. Basic helix-loop-helix (bHLH) transcription factors appear to fit this model, with the HLH domains mediating dimerization, the basic regions mediating DNA binding, and other modules controlling other functions such as transcriptional activation. We tested predictions of this model using forced dimers of bHLH proteins including E47 homodimers and MyoD:E47 heterodimers and found that protein dimers containing complete bHLH domains but lacking other regions of E47 have only 20% of the DNA binding ability and transcriptional transactivation activity of wild-type dimers. These results demonstrate that the bHLH domains do not function as completely independent DNA binding modules. In addition, these results demonstrate that the transcriptional activation domains from a single bHLH protein are sufficient to activate transcription.
3T3 Cells↗
Dual reciprocity boundary element method for solving thermal wave model of bioheat transfer.
The newly developed dual reciprocity boundary element method (DRBEM) was extended to solve the thermal wave model of bioheat transfer (TWMBT) and a practical algorithm was established. A preliminary simulation of the temperature evolution in a two dimensional zone under certain boundary conditions and micro wave heating was conducted as a numerical illustration for the method and some meaningful conclusions were drawn. The validity of DRBEM was testified through a comparison with finite difference method (FDM) under one-dimensional calculation. Owing to its unique advantages like not confined by the complex shape of biological bodies, no need of discretization of the inner domain, save vast CPU time and easy to deal with different bioheat models, DRBEM may become an important approach for predicting and controlling the transient temperature field of biological bodies under hyperthermia or hypothermia.
Algorithms↗
Early parental loss and personal control in later life.
There has been a considerable amount of research on the impact of early parental loss on children and younger adults, but far fewer studies have examined whether the effects of this early traumatic event extend into late life as well. The purpose of this research was to see whether early parental loss is associated with diminished feelings of personal control among older adults who participated in a nationwide survey (N = 519). In the process of examining this relationship, a conceptual model was developed and tested to attempt to explain why early loss may exert this effect. This model tests the following theoretical sequence. First, it is hypothesized that early parental loss is associated with lower levels of educational attainment and that people with limited schooling are more likely to encounter financial problems in later life. Finally, this model predicts that greater financial strain is in turn associated with diminished feelings of personal control among older adults. Subsequent analyses of this model provide empirical support for these theoretical linkages.
Aged↗
Association of fish intake and survival in a cohort of incident dialysis patients.
Multiple studies in the general population have shown cardioprotective and survival benefits associated with dietary fish intake, but little is known about outcomes associated with dietary fish intake in patients with chronic renal failure. We investigated fish consumption and survival in 216 incident dialysis patients. Fish consumption was identified in a 24-hour dietary recall and a 3-day food diary collected at baseline (near treatment start) and a 3-day food diary collected 1 year later. Patients who reported fish intake had higher average serum albumin levels at baseline than patients who did not report fish intake. Patient survival was followed up for an average of 3 years from baseline. In univariate Cox regression models, younger age, black race, peritoneal dialysis rather than hemodialysis as initial treatment modality, absence of cardiovascular comorbidity, higher self-assessed physical functioning, and fish consumption were significantly associated with patient survival. A multivariable Cox proportional hazards regression analysis showed that dietary fish consumption independently predicted patient survival, controlling for all other variables in the model. In multivariable analysis, patients who were younger, black, and had higher mental health scores at baseline also had a significantly decreased mortality risk. Patients who reported fish consumption were approximately 50% less likely to die during the study interval. Health outcomes associated with fish consumption merit continued study in patients with chronic renal failure.
Adolescent↗
A mathematical model quantifying the impact of antibiotic exposure and other interventions on the endemic prevalence of vancomycin-resistant enterococci.
BACKGROUND: Mathematical modeling can be used to describe the interdependent and dynamic interactions that contribute to the transmission dynamics of vancomycin-resistant enterococci (VRE). A model was developed to quantify the contribution of antibiotic exposure and of other modifiable factors to the dissemination of VRE in the hospital setting. METHODS: The model consists of 4 compartments: patients colonized with VRE receiving and not receiving antibiotics and uncolonized patients receiving and not receiving antibiotics. A series of differential equations describe the movement between these compartments. Baseline parameter estimates were obtained from pharmacy, infection-control, and clinical databases. RESULTS: The main predictions of this model are that (1) preventing the initiation or enhancing the discontinuation of unnecessary antimicrobial therapy will have a greater impact if it is targeted to patients who are not colonized with VRE; (2) increasing the number of patients harboring VRE at the time of hospital admission substantially increases the endemic prevalence of VRE; and (3) eliminating the influx of VRE results in the eradication of this pathogen from the hospital. A decrease in the endemic prevalence of VRE also occurs with a decrease in the length of hospital stay of colonized patients, increased hand hygiene compliance, and a lower ratio of health-care workers : patients. CONCLUSION: This mathematical model provides a framework to assist in targeting necessary interventions aimed at limiting the spread of VRE.
Anti-Bacterial Agents↗
Sustained and selective attention as measures of genetic liability to schizophrenia.
We tested for a relationship between attention and genetic liability to schizophrenia. Samples of probands with DSM-IV schizophrenia (n=20), their well first-degree relatives (n=40) and healthy controls (n=82) were tested using measures of sustained attention (degraded-stimulus continuous performance test: DS-CPT) and selective attention (spatial negative priming task). Assuming a liability-threshold model, we predicted that probands would display greater attentional decrements than controls and that the relatives would show intermediate levels of decrement. We did not observe the predicted pattern of effect using either measure, although the probands showed a trend towards less negative priming. However, our results may have been affected by self-selection bias in probands and relatives and clinical heterogeneity among probands, which could have reduced our power to detect effects.
Adolescent↗
Application of a calibration method provides more realistic results for a finite element model of a lumbar spinal segment.
BACKGROUND: An important step in finite element modeling is the process of validation to derive clinical relevant data. It can be assumed that defect states of a finite element model, which have not been validated before, may predict wrong results. The purpose of this study was to show the differences in accuracy between a calibrated and a non-calibrated finite element model of a lumbar spinal segment for different clinical defects. METHODS: For this study, two geometrically identical finite element models were used. An in vitro experiment was designed, deriving data for the calibration. Frequently used material properties were obtained from the literature and transferred into the non-calibrated model. Both models were validated on three clinical defects: bilateral hemifacetectomy, nucleotomy and interspinous defects, whereas in vitro range of motion data served as control points. Predictability and accuracy of the calibrated and non-calibrated finite element model were evaluated and compared. FINDINGS: Both finite element models could mimic the intact situation with a good agreement. In the defects, the calibrated model predicted motion behavior with excellent agreement, whereas the non-calibrated model diverged greatly. INTERPRETATION: Investigating the biomechanical performance of implants and load distribution of different spinal structures by numerical analysis requires not only good agreement with the intact segment, but also with the defect states, which are initiated prior to implant insertion. Because of more realistic results the calibration method may be recommended, however, it is more time consuming.
Finite Element Analysis↗
A conformation hypothesis for the suppressor and promoter functions of p53 in cell growth control and in cancer.
Cancer is a genetic disease caused by defective control of cell proliferation. As cancer cells divide, the genetic defect is inherited by each daughter cell, leading to tumour development with possible progression to malignancy. The identification of those genes linked with cancer is essential for our understanding of the regulation of cell proliferation and for the therapeutic management of cancer cell growth. Recent studies have revealed that p53 is the most commonly affected gene in human cancer. It is a single copy gene and functions in the regulation of cell proliferation. Mutation of p53 is linked with tumour development, and this may involve abnormal functioning of mutant p53 protein. A mutant allele of p53 is functionally temperature-sensitive and can promote or suppress cell proliferation. The tertiary structure of the mutant protein is also sensitive to temperature and adopts promoter and suppressor forms of p53. A conformation model for the functioning of p53 proposes that wild-type p53 is induced to change from suppressor to promoter form during the cell growth response. This model predicts that any mutation that deregulates the normal control of p53 conformation may lead to cancer.
Cell Division↗
Stomatal control and hydraulic conductance, with special reference to tall trees.
A better understanding of the mechanistic basis of stomatal control is necessary to understand why modes of stomatal response differ among individual trees, and to improve the theoretical foundation for predictive models and manipulative experiments. Current understanding of the mechanistic basis of stomatal control is reviewed here and discussed in relation to the plant hydraulic system. Analysis focused on: (1) the relative role of hydraulic conductance in the vicinity of the stomatal apparatus versus whole-plant hydraulic conductance; (2) the influence of guard cell inflation characteristics and the mechanical interaction between guard cells and epidermal cells; and (3) the system requirements for moderate versus dramatic reductions in stomatal conductance with increasing evaporation potential. Special consideration was given to the potential effect of changes in hydraulic properties as trees grow taller. Stomatal control of leaf gas exchange is coupled to the entire plant hydraulic system and the basis of this coupling is the interdependence of guard cell water potential and transpiration rate. This hydraulic feedback loop is always present, but its dynamic properties may be altered by growth or cavitation-induced changes in hydraulic conductance, and may vary with genetically related differences in hydraulic conductances. Mechanistic models should include this feedback loop. Plants vary in their ability to control transpiration rate sufficiently to maintain constant leaf water potential. Limited control may be achieved through the hydraulic feedback loop alone, but for tighter control, an additional element linking transpiration rate to guard cell osmotic pressure may be needed.
Models, Biological↗
Predicting diabetic control from competence, adherence, adjustment, and psychopathology.
OBJECTIVE: To determine what psychological and behavioral factors were most predictive of diabetic control. METHOD: Seventy-nine youths with diabetes were assessed cross-sectionally, using youths' reports of self-esteem, anxiety, and attitudes about diabetes, and parents' reports of competence and psychopathology (from the Child Behavior Checklist) and diabetic adherence as independent variables. Glycosylated hemoglobin A1c was the dependent variable, reflecting diabetic control. After the effects of several background variables were partialed out, a principal-components analysis grouped the substantive variables into three larger components. RESULTS: Among the background variables, duration of illness and family size significantly predicted diabetic control. Among substantive components, Competence/Adherence (including Total Competence, dietary compliance, and frequency of blood glucose checks) was highly predictive of diabetic control, primarily due to the effect of Total Competence. Adjustment (including self-esteem, anxiety levels, and attitudes about diabetes) and Psychopathology were less predictive. A model was constructed showing the relationships between these predictive components and diabetic control. CONCLUSIONS: In this generally well-adjusted sample, that Total Competence, more than other measures, predicted diabetic control suggests it could be used by clinicians to anticipate diabetic youths at risk.
Adolescent↗
A model to simulate the impact of timing, coverage and transmission intensity on the effectiveness of indoor residual spraying (IRS) for malaria control.
OBJECTIVE: (i) To develop a temperature- and rainfall-driven model of malaria transmission capable of prediction. (ii) To use the model to examine the relationship between the intervention timing and transmission intensity on the effectiveness of indoor residual spraying (IRS). METHODS: A dynamic model of malaria transmission was developed from existing models of malaria transmission dynamics. The model was used to retrospectively predict actual malaria cases from Hwange district in Zimbabwe using actual meteorological and IRS timing and coverage data. Simulations of alternative intervention scenarios (timing and coverage) examined the effectiveness of earlier and later interventions, at higher and lower coverage levels in epidemic and non-epidemic years. FINDINGS: The model was able to predict actual malaria cases in Hwange over a four-and-a-half-year period with a lead time of 4 months (e.g. January rainfall and temperature predicts April malaria) and a correlation coefficient of 0.825 (r(2) = 0.6814). The IRS simulations show that the marginal benefits of increasing IRS coverage are higher in high-transmission (HT) years relative to lower transmission years. This implies that over a period of years, maximum impact could be achieved with a given quantity of insecticide by increasing coverage in HT years. However, the model also shows that earlier spraying is more effective in all years, especially so in epidemic years, and that IRS has limited impact if it is carried out too late in relation to peak transmission. CONCLUSION: Temperature- and rainfall-driven models of malaria transmission have the potential to predict malaria epidemics. Early intervention based on prior knowledge of the magnitude of the malaria season can be more effective and efficient than carrying out routine activities every year. Malaria control planners need improved access to the technology that would allow them to better predict malaria epidemics and develop Malaria Early Warning Systems (MEWS). MEWS can then be linked to intervention planning to reduce the devastating impact of malaria epidemics on populations.
Animals↗
Prognostic factors and outcome after different types of resection for temporal lobe epilepsy.
OBJECT: It is unknown whether different resection strategies for temporal lobe epilepsy (TLE) produce alterations in seizure control or neuropsychological performance. METHODS: A series of 321 patients who underwent surgery for TLE between 1989 and 1997 was submitted to a uni- and multifactorial analysis of clinical, electrophysiological, neuroimaging, neuropsychological, and surgical factors to determine independent predictors of outcome. Until 1993, most patients with TLE underwent standard anterior temporal lobectomy (ATL); beginning in 1993, surgical procedures were increasingly restricted to lesions detected on magnetic resonance (MR) imaging and the presumed epileptogenic foci: for example, amygdalohippocampectomy (AH) or lesionectomy/corticectomy began to be used more often. The mean follow-up duration in this study was 38 months. Two hundred twenty-seven patients were classified as seizure free (70.7%), and 36 patients had rare and nondisabling seizures (11.2%); these groups were summarized as having good seizure control (81.9%). Twenty-four patients attained more than 75% improvement (7.5%), and no worthwhile improvement was seen in 34 cases (10.6%); these groups were summarized as having unsatisfactory seizure control (18.1%). On unifactorial analysis the following preoperative factors were associated with good seizure control (p < 0.05): single and concordant lateralizing focus on electroencephalography studies, low seizure frequency, absence of status epilepticus, concordant lateralizing memory deficit, clear abnormality on MR images, suspected ganglioglioma or dysembryoplastic neuroepithelial tumor (DNT), and absence of dysplasia on MR images. Stepwise logistic regression revealed a model containing five factors that were predictive for good seizure control (p < 0.1): 1) clear abnormality on MR images; 2) absence of status epilepticus; 3) MR imaging-confirmed ganglioglioma or DNT; 4) concordant lateralizing memory deficit; and 5) absence of dysplasia on MR images. Seizure outcome was mainly correlated with diagnosis and clinical factors. No significant differences were found regarding different resection types performed for comparable tumors. Neuropsychological testing revealed better postoperative results after limited resections compared with standard ATL, especially with regard to attention level, verbal memory, and calculated total neuropsychological performance. CONCLUSIONS: Different strategies for surgical approaches in TLE result in equally good outcomes. Seizure outcome is mainly dependent on the diagnosis and clinical factors, whereas the neuropsychological results are more beneficial after resections limited to an epileptogenic lesion and focus.
Adolescent↗
Correcting the QT interval for changes in HR in pre-clinical drug development.
OBJECTIVES: Estimation of possible cardiovascular side effects belongs to the safety assessment of every drug candidate. Drug-induced prolongation of the QT interval can result in life-threatening ventricular arrhythmia. In pre-clinical drug development, animal experiments are used to study this possible effect. Researchers have become aware that correction formulae derived for human beings are not applicable to animal experiments. METHODS: We investigated some of the proposed models by comparing the outcomes of the analyses on the same data. The data was derived from telemetry measurements on Labrador dogs. We propose the use of both the correlation with heart rate (or RR interval) and a measure of predictive performance. As a sufficiently large number of observations were available, the data was subdivided into a training and a test set. The training set serves to estimate the respective parameters while the test set is used to determine the performance of the model. Here, a kind of PRESS statistic was used. Next, the models were considered for treated animals, using the estimated parameters. Both positive and negative controls were used. CONCLUSIONS: Most models under consideration performed quite well. These models eliminated the correlation for the most part and were reasonably predictive. Furthermore, they reliably differentiate between positive and negative controls. The next steps in identifying the best correction will be to consider additional compounds as well as other species to validate our current results.
Animals↗
User-friendly models of the costs and efficacy of tsetse control: application to sterilizing and insecticidal techniques.
An interactive programme, incorporating a deterministic model of tsetse (Diptera: Glossinidae) populations, was developed to predict the cost and effect of different control techniques applied singly or together. Its value was exemplified by using it to compare: (i) the sterile insect technique (SIT), involving weekly releases optimized at three sterile males for each wild male, and (ii) insecticide-treated cattle (ITC) at 3.5/km(2). The isolated pre-treatment population of adults was 2500 males and 5000 females/km(2); if the population was reduced by 90%, its growth potential was 8.4 times per year. However, the population expired naturally when it was reduced to 0.1 wild males/km(2), due to difficulties in finding mates, so that control measures then stopped. This took 187 days with ITC and 609 days with SIT. If ITC was used for 87 days to suppress the population by 99%, subsequent control by SIT alone took 406 days; the female population increased by 48% following the withdrawal of ITC and remained above the immediate post-suppression level for 155 days; the vectorial capacity initially increased seven times and remained above the immediate post-suppression level for 300 days. Combining SIT and ITC after suppression was a little faster than ITC alone, provided the population had not been suppressed by more than 99.7%. Even when SIT was applied under favourable conditions, the most optimistic cost estimate was 20-40 times greater than for ITC. Modelling non-isolated unsuppressed populations showed that tsetse invaded approximately 8 km into the ITC area compared to approximately 18 km for SIT. There was no material improvement by using a 3-km barrier of ITC to protect the SIT area. In general, tsetse control by increasing deaths is more appropriate than reducing births, and SIT is particularly inappropriate. User-friendly models can assist the understanding and planning of tsetse control. The model, freely available via http://www.tsetse.org, allows further exploration of control strategies with user-specified assumptions.
Animals↗