Triage

Appropriate triage is essential for evaluating and sorting out individuals who may need immediate treatment. Once health care responders suspect radiation exposure, they should (2,5,8)  

Immediate PI) casualties who require life-saving care within a short time, when that care is available and of short duration. 

Delayed P2) casualties with severe injuries who are in need of major or prolonged surgery or other care and who wiU require hospitalisation, but delay of this care will not adversely affect the outcome of the injury. 

Minimal P3) casualties who have minor injuries, can be helped by non-physician medical personnel and will not be evacuated to hospital. 

Expectant (P4) casualties with severe life-threatening injuries who would not survive with optimal medical care, or casualties whose injuries are so severe that their chance of survival does not justify expenditure of resources. 

A modification of this system to the management of toxic trauma is as follows  

Conventionally, casualties are divided into the categories shown in Table 2.1. 

These casualties require immediate life-saving treatment. 

These casualties require significant intervention as soon as possible. Delayed category 

These patients will require medical intervention, but not with any urgency. 

Expectant patients are those whose injuries are so severe that attempting to save them would divert precious resources from other casualties with a greater chance of survival, with no significant chance of a successful outcome. The decision to invoke the expectant category must be taken at silver level and preferably only after discussion with gold command. 

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Triage is a searchable database of scientific studies on the health and environmental effects of toxic chemicals related to Section 8(e) of TSCA. 

Hit Triage Medicinal Chemistry Strategies to Improve the Odds of Success in Discovery... 

The potential sources of the compounds that are evaluated in a hit triage process are described in other chapters in this volume. These sources may include a high throughput screen (HTS) of a diverse compound collection, a targeted screen of... 

Fig. 1 Different sources of hits typically provide different distributions of number of hit compounds and amount known (and relevant) about those compounds, each of which contributes to the decision making process of hit selection and hit triage...

Fig. 2 Hit triage decision making requires inputs of experimental and calculated data and medicinal chemistry experience and expertise to arrive at an assessment of the probability of advancing individual chemical series...

HTS data and secondary screening for hit validation and determination of kinetic on/off rates. These data have been successfully incorporated into hit triage by enhancing the understanding of SAR differences between potential scaffolds [24]. In this example, those differences allowed informed decision making in the choice of which series to pursue and which to deprioritize. 

Because the goal of hit triage is to identify chemical series that hold promise for further optimization, an approach to characterize the ADME properties of a series, not just individual compounds is often useful. Where possible, characterizing the structure-ADME property relationship, in much the same way that a structure-potency relationship is defined, can be valuable for assessing the probability that a given structural series can be successfully optimized. The goals of this ADME property characterization are twofold (1) to identify specific structural features that may be liabilities (benefits), and (2) to identify general structure-ADME property correlations. 

From an early drug discovery and hit triage perspective, a simplification that is typically made is to focus initially on CYP metabolism that occurs in the fiver. This simplification is appropriate for the majority of compounds - some compounds will be cleared by other mechanisms, but it is generally assumed that they must be relatively stable to CYP metabolism to achieve a desirable PK profile. 

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