3-Pyridyloxypropanolamine agonists of the beta 3 adrenergic receptor with improved pharmacokinetic properties.

Pyridyloxypropanolamines L-749,372 (8, beta 3 EC50 = 3.6 nM) and L-750,355 (29, beta 3 EC50 = 13 nM) are selective partial agonists of the human receptor, with 33% and 49% activation, respectively. Both stimulate lipolysis in rhesus monkeys (ED50 = 2 and 0.8 mg/kg, respectively), with minimal effects on heart rate. Oral bioavailability in dogs, 41% for L-749,372 and 47% for L-750,355, is improved relative to phenol analogs.

The effect of managed care on ICU length of stay: implications for medicare.

OBJECTIVE: To determine whether insurance status (managed care vs traditional commercial and Medicare) influences resource consumption (as measured by length of stay [LOS]) in the intensive care unit (ICU). DESIGN: Retrospective analysis of the 1992 Massachusetts state hospital discharge database, using prospectively developed and validated risk-stratification models. SETTING: All nonfederal hospitals in Massachusetts. SUBJECTS: Of all adult hospitalizations where an ICU stay was incurred (n=104270), we selected those covered by 1 of 4 payer groups (n=88050): (1) commercial fee-for-service (patients aged <65 years); (2) commercial managed care (patients aged <65 years); (3) traditional Medicare (patients aged >/=65 years); and (4) Medicare-sponsored managed care (patients aged >/=65 years). MAIN OUTCOME MEASURE: Mean ICU LOS. ANALYSIS: The ICU LOS regression models were constructed using split-halves validation to adjust for differences in age, sex, severity of illness, diagnosis, discharge status, and payer. Separate models were constructed for those younger than 65 years and those aged 65 years or older. Robustness of the models was explored using goodness of fit and correlation. The effect of payer on hospital mortality was also explored using logistic regression. Observed minus predicted mean ICU LOS and mortality rates were correlated with managed care penetration at the hospital level. RESULTS: The ICU LOS models performed well (R2=0.84 and R2L [likelihood ratio statistic]=0.92 for the development set, and R2=0.83 and R2L=0.89 for the validation set). Significant covariables affecting LOS included age, severity of principal illness, comorbidity, reason for admission, and discharge status (P<.001 for each). Among the cohort younger than 65 years (n=27805), although unadjusted mean ICU LOS was shorter (2.9 vs 3.43 days; P<.05) for those covered by managed care organizations, payer status had no independent effect on ICU LOS (P=.48). Among those older than 65 years, there was neither a difference in unadjusted ICU LOS (3.94 vs 3.88 days; P>/=.05) nor an independent effect of payer on ICU LOS (P=.35). Unadjusted mortality was lower among managed care patients (3.9% vs 5.1% in patients aged <65 years [P<.05] and 8.7% vs 12.1% in patients aged > or = 65 years [P<.05]). Age, severity of principal diagnosis, comorbidity, and reason for admission significantly influenced mortality (P<.001). After controlling for these factors with the mortality model (R2L=0.92 and 0.89, C statistic [12 df]=8.45 and 17.58, and P=.75 and .13 [where a large P reflects good agreement] for the development and validation sets, respectively), payer continued to have a small but significant effect on mortality (odds ratios ranging from 1.67 at 0.1% probability of death to 1.11 at 30% probability of death.) Managed care penetration among the commercially insured varied across hospitals (n=82) from 0% to 68%. There was no correlation between managed care penetration and either ICU LOS (R2=0.04; P=.09) or mortality (R2=0.0; P=.88). CONCLUSIONS: Though patients covered under managed care consume fewer ICU resources, this appears to be primarily attributable to a difference in patient-related factors. Thus, as managed care case mix changes in the future to include sicker and older patients, the initial advantages of reduced resource consumption may diminish.

An evaluation of the potential cost reductions resulting from the use of clodronate in the treatment of metastatic carcinoma of the breast to bone.

The reported studies of clodronate in the management of osteolytic bone metastases suggest a significant palliative role for this drug. In this paper we report on analysis of the hospital costs associated with the management of osteolytic metastatic disease, and an estimate of the potential cost/benefit impact of clodronate therapy. Two separate patient populations were assessed retrospectively. The first, a sample of 120 patients with symptomatic bone metastases who had died from metastatic breast cancer over the period 1980-1990, was used to define the natural history of the disease. A second non-concurrent patient group of 337 patients was evaluated to determine the mean cost of all hospital admissions for patients with bone metastases from breast carcinoma. The length of stay and costs for hospital admissions related to the bone metastases were also assessed, in addition to the cost of out-patient radiation therapy. Our cost/benefit value analysis suggests that there are significant savings to be gained from the use of clodronate if a 20% or greater reduction occurs in the incidence of fractures, hypercalcaemia, and hospital-based treatment for pain control (via radiotherapy). We also speculate that the quality of life of patients with osteolytic bone metastases may be improved with this agent.

Comparison of performances of transfer students and first-year acceptees.

Graduates of the Medical College of Pennsylvania during 1970-1977 were studied to determine the impact of three types of preclinical training on prelicensure clinical performance. The 586 students who comprised these groups consisted of 471 students admitted to the first year, 53 students admitted with advanced standing from U.S. medical or graduate programs, and 62 students admitted with advanced standing from foreign medical schools. Academic performances among the groups differed as measured by scores on the examinations of the National Board of Medical Examiners. However, perceived clinical performances of both transfer groups, as measured by honors awarded in year four and by first-year residency evaluation, were on a par with that of the original matriculants.