Objective To characterize the population pharmacokinetics (PK) of oral baclofen and assess impact of patient-specific covariates in children with cerebral palsy (CP) in order to support its clinical use. Subjects design Children (2-17 years of age) with CP received a dose of titrated oral baclofen from 2.5 mg 3 times a day to a maximum tolerated dose of up to 20 mg 4 times a day. PK sampling followed titration of 10-12 weeks. Serial R- and S-baclofen plasma concentrations were measured for up to 16 hours in 49 subjects. Population PK modeling was performed using NONMEM 7.1 (ICON PLC; Ellicott City, Maryland). Results R- and S-baclofen showed identical concentration-time profiles. Both baclofen enantiomers exhibited linear and dose/kg-proportional PK, and no sex differences were observed. Average baclofen terminal half-life was 4.5 hours. A 2-compartment PK model with linear elimination and transit absorption steps adequately described concentration-time profiles of both baclofen enantiomers. The mean population estimate of apparent clearance/F was 0.273 L/h/kg with 33.4% inter-individual variability (IIV), and the apparent volume of distribution (Vss/F) was 1.16 L/kg with 43.9% IIV. Delayed absorption was expressed by a mean transit time of 0.389 hours with 83.7% IIV. Body weight, a possible genetic factor, and age were determinants of apparent clearance in these children. Conclusion The PK of oral baclofen exhibited dose-proportionality and were adequately described by a 2-compartment model. Our population PK findings suggest that baclofen dosage can be based on body weight (2 mg/kg per day) and the current baclofen dose escalation strategy is appropriate in the treatment of children with CP older than 2 years of age.

BackgroundHormone receptor and HER-2/neu discordance between the primary lesion and first metastasis has been reported. This study was performed to determine further biomarker discordance rates between the first and subsequent metastatic breast cancer lesions.MethodsWe performed a retrospective review of paired biomarkers from primary breast cancers compared to first reported and subsequent metastases from 103 patients with breast cancer. The estrogen receptor (ER), progesterone receptor (PR), and HER-2/neu status were reported at all three time points. In addition, hormone, cytotoxic, and targeted treatments were recorded for primary and metastatic disease, and survival was determined.ResultsBetween the primary and first metastases, discordance rates for ER, PR, and HER-2/neu were 15.8%, 33.7%, and 14.3%, respectively. There was discordance between the first and second metastases for the ER receptor in 18.8%, PR receptor in 19.8%, and HER-2/neu in 10.7%. Overall, there was discordance between the primary tumor and either the first or second metastases for ER in 27.7%, PR receptor in 40.7%, and HER-2/neu in 19.6% of cases. Discordance of either ER or PR affected survival, with worse survival experienced by those patients with all three hormone receptors remaining negative, and intermediate survival reported for those with discordant tumors (ER χ2=14.27, p=0.0008; PR χ2=11.31, p=0.0035). There was no difference in survival for patients whose HER-2/neu tumors were discordant.ConclusionThis study demonstrated that continued metastatic disease evolution may be associated with different tumor biology and that studies of metastatic lesions appear warranted, especially if targeted therapy is an option.

Burnout in social services professionals has been defined as a syndrome of emotional exhaustion, depersonalization, and reduced personal accomplishment. The pediatric critical care nurse is especially vulnerable to this phenomenon when exposed to prolonged, chronic suffering of a patient. The rewarding aspect of caring for the critically ill child who recovers from significant affliction is not experienced when caring for the "chronic child." This article reviews the dynamics of chronicity in pediatric critical care and explores protective strategies for burnout management. Several of Jean Watson's carative factors that define her human care philosophy provide the conceptual framework for the approaches outlined.

In Western countries, demographic trends indicate an increase in the aging population well into the next century. Because of declining health, many older adults will benefit from residence in assisted living (AL). The purpose of this qualitative study was to explore the experience and contextual influences in everyday decision-making of four older adults in AL using a case study method. Several themes emerged as significant in older adult satisfaction with everyday decision-making (i.e., trigger event, level of physical functioning, inside and outside support systems, past patterns of decision-making). Strategies for assessing and strengthening these contextually relevant factors are discussed.

This project demonstrated the feasibility of designing, marketing a brief workshop, and positively impacting communication and documentation skills.