Darbepoetin administration to neonates undergoing cooling for encephalopathy: a safety and pharmacokinetic trial.

BACKGROUND: Despite therapeutic hypothermia, neonates with encephalopathy (NE) have high rates of death or disability. Darbepoetin alfa (Darbe) has comparable biological activity to erythropoietin, but has extended circulating half-life (t(1/2)). Our aim was to determine Darbe safety and pharmacokinetics as adjunctive therapy to hypothermia. STUDY DESIGN: Thirty infants (n = 10/arm) ≥36 wk gestation undergoing therapeutic hypothermia for NE were randomized to receive placebo, Darbe low dose (2 µg/kg), or high dose (10 µg/kg) given intravenously within 12 h of birth (first dose/hypothermia condition) and at 7 d (second dose/normothermia condition). Adverse events were documented for 1 mo. Serum samples were obtained to characterize Darbe pharmacokinetics. RESULTS: Adverse events (hypotension, altered liver and renal function, seizures, and death) were similar to placebo and historical controls. Following the first Darbe dose at 2 and 10 µg/kg, t(1/2) was 24 and 32 h, and the area under the curve (AUC(inf)) was 26,555 and 180,886 h*mU/ml*, respectively. In addition, clearance was not significantly different between the doses (0.05 and 0.04 l/h). At 7 d, t(1/2) was 26 and 35 h, and AUC(inf) was 10,790 and 56,233 h*mU/ml*, respectively (*P < 0.01). CONCLUSION: Darbe combined with hypothermia has similar safety profile to placebo with pharmacokinetics sufficient for weekly administration.

A revised back compressive force estimation model for ergonomic evaluation of lifting tasks.

Occupational back pain and injury are common and costly issues. Biomechanical models are often used to quantify job risk by estimating back muscle forces. In general, the most accurate models are also the most complex, creating demand for models that are both straightforward and accurate. An existing, basic hand-calculation back compressive force estimation model (HCBCF v1.0) was revised in two iterations to reduce the error induced by original simplifying assumptions. Lifting tasks (n=6000) from observational data were used to compare the HCBCF models with the University of Michigan 3D Static Strength Prediction Program (3DSSPP) The greatest r(2) (0.97) between the HCBCF v1.2 and the 3DSSPP was achieved with gender-specific equations designed to account for differences between males and females and a more detailed estimation of torso flexion angle and upper body mass center location. This gender-specific back compression and risk estimation model is a relatively simple alternative to computer-based back compressive force models. In addition the hand-calculation can be used as a general survey tool to determine which jobs should be analyzed with more sophisticated computer-based models.