Arbitrary clinical response

Figure 5 Comparison of tachyphylaxis phenotypes in the static versus dynamic models of receptor regulation. The models differ as to whether endogenous agonist pre-regulates receptor function prior to exogenous agonist exposure. The predicted clinical effect (tachyphylaxis) differs depending on the model. For / 2AR, SNP A is the Argl6 receptor and SNP B is Gly 16. The bars represent arbitrary physiologic responses, such as FEV],...

Several fundamental problems with the mismatch approach exist and may help to explain the conflicting data. Eirst, there is no consensus definition for what constitutes a significant mismatch [112,116,131]. The 20% PWI/DWI mismatch is commonly used but it remains an arbitrary value. A posthoc analysis of 45 patients from the DEFUSE study found that a PWE DWI ratio of 2.6 yielded the highest sensitivity (90%) and specificity (83%) for identifying a favorable clinical response to early reperfusion [135]. Additionally, there is no consensus as to which perfusion parameter should be employed in defining the mismatch [131,... 

Patients with malignant-accelerated hypertension can usually be managed by oral therapy. Patients who are seen in a nursing home or clinic, whose BP is found to be above some arbitrary danger level like a BP of 180/120 should not automatically be given nifedipine sublingually. Indiscriminate use of nifedipine sublingually could lead to a major catastrophe like myocardial infarction or cerebrovascular episodes. Nifedipine activates sympathetic response and leads to precipitous drops of blood pressure followed by rebound hypertension. 

Response to P2-agonists ean be expressed as the change in FEVi from baseline after either a single dose or 12 weeks of treatment. The American Thoracic Society defines an increase of more than 12% and at least 200 mL in FEVi as a significant bronchodilator response [7], An increase of 8% or less is considered within measurement variability. A 12% to 15% increase in FEVi is the common arbitrary threshold used in clinical research reports to separate patients who respond well to p2-agonists from those who respond poorly [13]. 

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