Age and function differences in shared task performance: walking and talking.
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Adolescent↗
Biomedical subjects
Kathleen Williams
Publications and source records attributed to Kathleen Williams.
Management of diabetes during acute stroke and inpatient stroke rehabilitation.
OBJECTIVES: To summarize evidence on the impact of hyperglycemia on stroke outcomes and to present therapy algorithms for inpatient management in diabetic stroke patients. DATA SOURCES: Guidelines for inpatient management of diabetes were reviewed and extracted from a technical review and recommendations from 2 national diabetes and endocrine organizations. MEDLINE database searches were conducted using key words: stroke, diabetes, hyperglycemia, hypoglycemia, inpatient, hospitalized, treatment, outcomes, disability, self-management, and education. STUDY SELECTION: Studies were selected that specifically addressed the impact of the following in stroke patients: hyperglycemia and diabetes on rehabilitation outcomes, management strategies for hyperglycemia and diabetes, and strategies for facilitating diabetes self-management. DATA EXTRACTION: Two authors independently extracted data and management practices from selected articles and published practice guidelines. DATA SYNTHESIS: Diabetes is prevalent in stroke patients and results in poorer inpatient hospital and rehabilitation outcomes. Management of diabetes in stroke patients is further complicated by impairments in mobility and vision, necessitating accommodation strategies and tools for self-management. Optimal management of hyperglycemia using insulin or oral hypoglycemic agents results in reduced morbidity and mortality among diabetic inpatients. CONCLUSIONS: To achieve inpatient glycemic management targets, use of clinical management algorithms, self-management tools, and systems approaches such as diabetes management teams are useful.
Algorithms↗
A phase I study of oral BMS-275291, a novel nonhydroxamate sheddase-sparing matrix metalloproteinase inhibitor, in patients with advanced or metastatic cancer.
PURPOSE: BMS-275291 is a novel broad-spectrum inhibitor of matrix metalloproteinase (MMPs) rationally designed to spare a class of closely related metalloproteinases known as sheddases. Inadvertent sheddase inhibition is hypothesized to play a role in the dose-limiting joint toxicities occurring with hydroxamate-based MMP inhibitors. This trial was conducted to establish the recommended phase II dose; determine safety, toxicity, and pharmacokinetics of BMS-275291; and to assess potential markers of sheddase activity [tumor necrosis factor-alpha (TNFalpha) release and TNFalpha-RII shedding]. EXPERIMENTAL DESIGN: This was an open label, single arm, phase I study conducted at two centers. Patients with advanced or metastatic cancer were treated with once-daily oral BMS-275291 at doses escalating from 600 to 2400 mg/day. Six to eight patients/dose level were to be studied with the recommended phase II dose level expanded to a total of 15 patients. Pharmacokinetic sampling was performed on days 1, 15, and 29 at 0, 0.5, 1, 2, 4, 6, 8, and 24 h after dosing. Radiological tumor assessment was performed every 8 weeks. RESULTS: Forty-four evaluable patients were enrolled in this study with the most frequent tumor types being colorectal cancer and non-small cell lung cancer. Dose limiting toxicities were observed at 600 mg/day (one of eight patients with grade 3 transaminitis) and at 1200 mg/day (1 of 15 patients with grade 3 rash and grade 4 shortness of breath), both in the context of predisposing conditions. No dose-limiting toxicities occurred at 900, 1800, or 2400 mg/day. The most frequent adverse events considered possibly, probably, or definitely drug-related were joint toxicity (myalgia/arthralgia), rash, fatigue, headache, nausea, and taste change, all of which were mild, grade 1, grade 2, and not dose-limiting. No objective tumor responses were observed. Twelve of forty-four patients received treatment for 4+ months, six for 8+ months, three for >1 year. Desired trough levels of parent BMS-275291 were maintained with once daily dosing. The mean plasma concentration of parent BMS-275291 at trough exceeded the calculated in vitro IC(80) value for MMP-2 and IC(90) value for MMP-9 at the recommended phase II dose of 1200 mg/day. No major changes in serum concentrations of sheddase enzymatic products, TNFalpha or TNFalpha-RII, were observed. CONCLUSIONS: BMS-275291 is a nonhydroxamate MMP inhibitor with a novel mercaptoacyl zinc-binding group. In this study, plasma concentrations of BMS-275291 continuously exceeded in vitro MMP IC(50) values without dose-limiting joint toxicity. In this refractory patient population, a suggestion of disease stabilization was observed in 12 patients. On the basis of preclinical, clinical, and pharmacokinetic data, the recommended phase II dose for future study is 1200 mg/day.
Adult↗