Predictions prospective

Lerew, D. R., Schmidt, N. B., Jackson, R. J. (1999). Evaluation of psychological risk factors Prospective prediction of psychopathology during basic training. Military Medicine, 164, 509-513. 

In presenting the pharmacokinetic model for heparin some parameters were fitted to data on healthy volunteers while other parameters were arbitrarily chosen. To improve heparin therapy the pharmacokinetic modeling approach discussed here must be used in a prospective, predictive manner. By taking additional blood samples early on in heparin therapy data for each patient can be generated. One would measure such variables as heparin level, AT-III level, PTT, etc. Then, by using the model presented here or a more accurate model, parameters can be fitted (7J and the... 

The complex and often uncertain outcome of drug discovery and development processes requires the simultaneous optimization of several properties. It has now long been recognized that favorable potency and selectivity characteristics are not the sole hallmarks of a successful drug discovery program, nor is the safety profile considered to be the only hurdle to be overcome, although it is of paramount importance. The ability to prospectively predict the pharmacokinetics of new chemical entities in humans is a powerful means by which one can select for further development only those compounds with the potential to be successful therapeutic agents. 

LaGasse JM, Brantley MS, Leech NJ, Rowe RE, Monks S, Palmer JP, Nepom GT, McCulloch DK, Hagopian WA (2002) Successful prospective prediction of type 1 diabetes in schoolchildren through multiple defined autoantibodies an 8-year follow-up of the Washington State Diabetes Prediction Study. Diabetes Care, 25 505-511. 

Use of in vitro data to prospectively predict DDIs is diflhcult and some have proposed a relatively simple rank-order approach (Obach et ah, 2005). In this instance, a NCE is evaluated as an inhibitor of different CYP forms in vitro. Standardized ineubation conditions are employed, so that the ICsqS or for each CYP form are ranked in order of increasing potency. The CYP form with the lowest IC50 or K is evaluated first in the clinic. For example, the inhibition is greatest with CYP3A4, and then a midazolam clinical DDI study is initiated first. Other CYPs are followed up with suitable probe drugs as needed (Table 5.4). 

Chen Y, Jin JY, Mukadam S, Malhi V, Kenny JR. 2012. Application of IVIVE and PBPK modeling in prospective prediction of clinical pharmacokinetics strategy and approach during the drug discovery phase with four case studies. Biopharm Drug Dispos 33 85-98. 

As reviewed in the interest of sound design-procedure, the necessary creep information should be procured on the prospective material, under the conditions of product usage. In addition to the creep data, a stress-strain diagram, also at the conditions of product usage, should be obtained. The combined information will provide the basis for calculating the predictability of material performance in the designed product. 

Bradley P, Chivian D, Meiler J, Misura KMS, Rohl CA, Schief WR, et al. Rosetta predictions in CASP5 successes, failures, and prospects for complete automation. Proteins 2003 53 457-68. 

Model equations can be augmented with expressions accounting for covariates such as subject age, sex, weight, disease state, therapy history, and lifestyle (smoker or nonsmoker, IV drug user or not, therapy compliance, and others). If sufficient data exist, the parameters of these augmented models (or a distribution of the parameters consistent with the data) may be determined. Multiple simulations for prospective experiments or trials, with different parameter values generated from the distributions, can then be used to predict a range of outcomes and the related likelihood of each outcome. Such dose-exposure, exposure-response, or dose-response models can be classified as steady state, stochastic, of low to moderate complexity, predictive, and quantitative. A case study is described in Section 22.6. 

Specific predictive factors for outcome after surgical intervention have not been well defined in the literature. In one prospective, multicenter observational study of 95 patients, the state of consciousness was the only predictive factor retained in a logistic regression analysis." In this study, there was a 2.8-fold increased risk for poor outcome for each increase on a three-step scale (awake/drowsy, somnolent/ stuporous, and comatose), and good outcomes (modified Rankin Scale score <2) were achieved in 86%, 76%, and 47% of patients within each group, respectively. 

It is difficult to predict if a neurologically injured patient will successfully be extubated. Salam et alstudied 88 patients prospectively, measuring cough peak flow (CPF), endotracheal secretions, and the ability to complete four simple tasks prior to extubation. In patients who failed extubation, they had a lower CPF p = 0.03), higher amount of secretions (RR 3.0, 95% Cl 1.0-8.8), and diminished ability to complete the four simple tasks (RR 4.3, 95% Cl 1.8-10.4). 

The bulk of this paper will be concerned with the prospects of Ji-nitroso compound formation in the environment, and with environmental behaviors of selected nitroso compounds, as best we can describe or predict them from experimental work completed thus far. Obviously, once in the environment, a compound will to a large extent be subject to the same conditions whether it was formed there or introduced as a pesticide contaminant, and in this manuscript no attempt to differentiate between the two modes of introduction has been made. Such distinctions could, however, influence the location of a compound in the environment—say on a plant or soil surface if sprayed with a pesticide, admixed with soil if transported by leaching, etc., and some of the experiments cited will have been conceived with one or the other of the introduction modes in mind. 

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