Estimating the 95% effective defibrillation dose.

Minimum squared error (MinSE) testing protocols and a MinSE estimator are presented which accurately estimate the voltage that defibrillates 95% of the time (the ED95). The MinSE experimental procedures, presented in the form of lookup tables, detail the response to successful and unsuccessful trials. The lookup tables also show the ED95 estimates calculated from the observed results using the MinSE estimator. Two assumptions are required to develop the look-up tables: 1) the dose-response curve, chosen using a statistical analysis of a retrospective sample, and 2) the distribution of the ED95's in the population. The MinSE estimator and experimental procedure are examined in a prospective study of five dogs (19-25 kg, heart weights 139.3-236.9 gm) using nonthoracotomy implantable defibrillator electrodes and a biphasic defibrillation waveform (3.5 ms first phase, 2.0 ms second phase). Employing an ED95 population distribution assumption applicable to most implantable defibrillator electrodes and waveforms, e.g., the ED95 is between 0.0 and 800.0 V, the measured rms error was 15% of the mean measured ED95 for the MinSE, four test shock, ED95 estimates. If the protocols are designed with an ED95 population distribution assumption for animals of the same species and size, and defibrillation is constrained to one electrode configuration and waveform, the estimates improve by 3.8%. Using techniques from the Bayesian statistics literature, the MinSE approach can be extended to a variety of defibrillation parameter estimation problems.

Methacholine-induced cutaneous flare response: bivariate analysis of responsiveness and sensitivity.

Cutaneous reactions to allergens exhibit a sigmoid dose-response relationship. Available methods for evaluating the allergen skin-test response do not adequately account for the sigmoid curve. Methodologic factors handicap quantitative studies of allergens based on skin-test reactivity. This problem was evaluated with a pharmacologic agonist that mimics cutaneous reactivity. Epicutaneous tests with appropriate concentrations of methacholine were used to provoke flare responses in 84 healthy subjects. A novel hyperbolic tangent model of the sigmoid dose-response curve was used to estimate responsiveness (R) as the midpoint of the sigmoid curve. Sensitivity (C) was estimated as the agonist concentration yielding a flare response equivalent to R. Estimates of sensitivity were independent of estimates of responsiveness (r=-0.0565, p=0.6642). The geometric mean methacholine sensitivity among health subjects was 287 mM/L, and average methacholine responsiveness was 4.9 mm. The mathematic model used in these studies fitted observations surprisingly well (X2(84)=37.044, p greater than 0.95). Differences in methacholine sensitivity and responsiveness related to race, sex, and allergic and/or vasomotor tendencies were detected but were subtle and did not account for a significant portion of the variation among healthy subjects. This model may provide a useful method for quantifying cutaneous immediate hypersensitivity reactions in patients.