Tissue plasminogen activator (tPA) has been shown to improve 3-month outcome in stroke patients treated within 3 hours of symptom onset. The costs associated with this new treatment will be a factor in determining the extent of its utilization. Data from the NINDS rt-PA Stroke Trial and the medical literature were used to estimate the health and economic outcomes associated with using tPA in acute stroke patients. A Markov model was developed to estimate the costs per 1,000 patients eligible for treatment with tPA compared with the costs per 1,000 untreated patients. One-way and multiway sensitivity analyses (using Monte Carlo simulation) were performed to estimate the overall uncertainty of the model results. In the NINDS rt-PA Stroke Trial, the average length of stay was significantly shorter in tPA-treated patients than in placebo-treated patients (10.9 versus 12.4 days; p = 0.02) and more tPA patients were discharged to home than to inpatient rehabilitation or a nursing home (48% versus 36%; p = 0.002). The Markov model estimated an increase in hospitalization costs of $1.7 million and a decrease in rehabilitation costs of $1.4 million and nursing home cost of $4.8 million per 1,000 eligible treated patients for a health care system that includes acute through long-term care facilities. Multiway sensitivity analysis revealed a greater than 90% probability of cost savings. The estimated impact on long-term health outcomes was 564 (3 to 850) quality-adjusted life-years saved over 30 years of the model per 1,000 patients. Treating acute ischemic stroke patients with tPA within 3 hours of symptom onset improves functional outcome at 3 months and is likely to result in a net cost savings to the health care system.

We found measurements that reflected reduced size of the eye orbit to be a consistent feature discriminating FAS and controls across each study population. However, each population had a unique, though often overlapping, set of variables which discriminated the 2 groups, suggesting important ethnic differences in the presentation of FAS. It is possible that these differences were accentuated by the wide age distribution of the study subjects.

Directional asymmetry, the systematic differences between the left and right body sides, is widespread in human populations. Changes in directional asymmetry are associated with various disorders that affect craniofacial development. Because facial dysmorphology is a key criterion for diagnosing fetal alcohol syndrome (FAS), the question arises whether in-utero alcohol exposure alters directional asymmetry in the face. Data on the relative position of 17 morphological landmarks were obtained from facial scans of children who were classified as either FAS or control. Shape data obtained from the landmarks was analyzed with the methods of geometric morphometrics. Our analyses showed significant directional asymmetry of facial shape, consisting primarily of a shift of midline landmarks to the right and a displacement of the landmarks around the eyes to the left. The asymmetry of FAS and control groups differed significantly and average directional asymmetry was increased in those individuals exposed to alcohol in utero. These results suggest that the developmental consequences of fetal alcohol exposure affect a wide range of craniofacial features in addition to those generally recognized and used for diagnosis of FAS.

We have two objectives in this study: to demonstrate the utility of two summary anthropometric measures for quantifying craniofacial variation and to explore some of their potential uses by physicians and clinical morphologists in general. The Craniofacial Variability Index (CVI) is a summary anthropometric measure of facial "harmony." The mean z-score, based on craniofacial anthropometry, is a measure of overall facial size. Both add an objective component to the assessment of individual facial variation and allow us to place the individual along a scale of continuous variation with predetermined limits of "normality" based on a reference or control series. Our results suggest that these summary measures coincide well with clinical assessments of abnormality in 278 individuals representing five distinct syndromes (Brachmann-de Lange, Prader-Willi, Rubinstein-Taybi, Smith-Magenis, and Sotos), each of which has an associated craniofacial component. Although craniofacial variation is continuous and the normal and syndromic populations overlap to varying degrees, the syndromic cases can be characterized in a variety of ways by using CVI as a measure of facial harmony and Mean-Z as an indicator of overall facial size. Thus, these two-objective measures offer a novel and efficient means of assessing craniofacial variation, whether they are used as tools in the clinical evaluation of subjects or as a means of exploring the nature of craniofacial variation within or between syndromes.

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