Summary results indicate that risk of ischemic stroke is increased in current OC users, even with newer low-estrogen preparations. However, the absolute increase in stroke risk is expected to be small since incidence is very low in this population. JAMA. 2000;284:72-78

BackgroundAn analysis of NIH funding in 1996 found that the strongest predictor of funding, disability-adjusted life-years (DALYs), explained only 39% of the variance in funding. In 1998, Congress requested that the Institute of Medicine (IOM) evaluate priority-setting criteria for NIH funding; the IOM recommended greater consideration of disease burden. We examined whether the association between current burden and funding has changed since that time.MethodsWe analyzed public data on 2006 NIH funding for 29 common conditions. Measures of US disease burden in 2004 were obtained from the World Health Organization's Global Burden of Disease study and national databases. We assessed the relationship between disease burden and NIH funding dollars in univariate and multivariable log-linear models that evaluated all measures of disease burden. Sensitivity analyses examined associations with future US burden, current and future measures of world disease burden, and a newly standardized NIH accounting method.ResultsIn univariate and multivariable analyses, disease-specific NIH funding levels increased with burden of disease measured in DALYs (p = 0.001), which accounted for 33% of funding level variation. No other factor predicted funding in multivariable models. Conditions receiving the most funding greater than expected based on disease burden were AIDS ($2474 M), diabetes mellitus ($390 M), and perinatal conditions ($297 M). Depression ($719 M), injuries ($691 M), and chronic obstructive pulmonary disease ($613 M) were the most underfunded. Results were similar using estimates of future US burden, current and future world disease burden, and alternate NIH accounting methods.ConclusionsCurrent levels of NIH disease-specific research funding correlate modestly with US disease burden, and correlation has not improved in the last decade.

Background and Purpose-We sought to measure the overall rate of usage of tissue-type plasminogen activator (tPA) for ischemic stroke at academic medical centers, and to determine whether ethnicity was associated with usage. Methods-Between

Of the 11 stroke center elements recommended by the BAC, 7 were associated with increased tPA use. Institutions with a greater number of these seven features used tPA more often, suggesting these key elements may be most important for primary stroke center designation, at least in terms of identifying centers that deliver IV tPA frequently.

Purpose This study was designed to assess the effect of mitochondrial DNA (mtDNA) mutation T8993C on cone structure in a family expressing neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP) syndrome. Methods Five family members were studied, using clinical examination, nerve conduction studies, perimetry, optical coherence tomography (OCT) measures of central retinal thickness, and electroretinography. High-resolution images of cone structure using adaptive optics scanning laser ophthalmoscopy (AOSLO) were obtained in four subjects with stable fixation. Cone spacing was compared to 18 age-similar normal subjects and converted to z-scores at each location where unambiguous cones were identified. Tissue levels of T8993C mutant heteroplasmy in blood and hair follicles were quantified using real-time allele-refractory mutations system (ARMS) quantitative polymerase chain reaction (qPCR). Results Subjects expressing the T8993C mutation showed varying levels of disease severity. The subject with the lowest mutant load (42%–54%) showed no neurologic or retinal abnormalities. The remaining four subjects with over 77% mutant load all expressed severe neurologic and/or retinal abnormalities. AOSLO images revealed three patterns of cone spacing: pattern 1, normal; pattern 2, increased cone spacing within a contiguous cone mosaic; and pattern 3, patchy cone loss with increased cone spacing. Visual function was most severely affected in pattern 3. Conclusions High levels of T8993C mutant load were associated with severe neurologic or visual dysfunction, while lower levels caused no detectable abnormalities. Visual function was better in patients with a contiguous and regular cone mosaic. Patients expressing high levels of the mtDNA T8993C mutation show abnormal cone structure, suggesting normal mitochondrial DNA is necessary for normal waveguiding by cones.

Background and Purpose-Data supporting the efficacy of stroke center characteristics are limited. Methods-A questionnaire detailing stroke treatment practices was sent to 42 academic medical centers in the University Health Systems Consortium. In-hospital mortality of all emergency department admissions for ischemic stroke at these institutions was evaluated in a database of discharge abstracts during 1997-1999. Institutional characteristics were evaluated as predictors of in-hospital mortality after adjustment for age, sex, race, hospital treatment volume of ischemic stroke, and admission status (emergent, urgent, elective). Length of stay (LOS), total hospital charges, and frequency of tissue plasminogen activator (tPA) administration were evaluated as secondary outcomes. We used a multivariable method called generalized estimating equations, which broadens confidence intervals to adjust for clustering of variables at institutions. Results-Thirty-two institutions completed the questionnaire, and 29 of these were included in the database of discharge abstracts. In-hospital deaths occurred in 758 (7.0%) of the 10 880 ischemic stroke patients admitted through the emergency department. In-hospital deaths were less frequent at hospitals with a vascular neurologist (odds ratio

Point mutations at m.8993T>C and m.8993T>G of the mtDNA ATPase 6 gene cause the neurogenic weakness, ataxia and retinitis pigmentosa (NARP) syndrome, a mitochondrial disorder characterized by retinal, central and peripheral neurodegeneration. We performed detailed neurological, neuropsychological and ophthalmological phenotyping of a mother and four daughters with NARP syndrome from the mtDNA m.8993T>C ATPase 6 mutation, including 3-T brain MRI, spectral domain optical coherence tomography (SD-OCT), adaptive optics scanning laser ophthalmoscopy (AOSLO), electromyography and nerve conduction studies (EMG-NCS) and formal neuropsychological testing. The degree of mutant heteroplasmy for the m.8993T>C mutation was evaluated by real-time allele refractory mutation system quantitative PCR of mtDNA from hair bulbs (ectoderm) and blood leukocytes (mesoderm). There were marked phenotypic differences between family members, even between individuals with the greatest degrees of ectodermal and mesodermal heteroplasmy. 3-T MRI revealed cerebellar atrophy and cystic and cavitary T2 hyperintensities in the basal ganglia. SD-OCT demonstrated similarly heterogeneous areas of neuronal and axonal loss in inner and outer retinal layers. AOSLO showed increased cone spacing due to photoreceptor loss. EMG-NCS revealed varying degrees of length-dependent sensorimotor axonal polyneuropathy. On formal neuropsychological testing, there were varying deficits in processing speed, visual–spatial functioning and verbal fluency and high rates of severe depression. Many of these cognitive deficits likely localize to cerebellar and/or basal ganglia dysfunction. High-resolution retinal and brain imaging in NARP syndrome revealed analogous patterns of tissue injury characterized by heterogeneous areas of neuronal loss.Electronic supplementary materialThe online version of this article (doi:10.1007/s00415-010-5775-1) contains supplementary material, which is available to authorized users.

Interns are expected to teach medical students, yet there is little formal training in medical school to prepare them for this role. To enhance the teaching skills of our graduating students we initiated a 4‐hour “teaching to teach” course as part of the end of the fourth‐year curriculum. Course evaluations demonstrate that students strongly support this program (overall ratings 2000 to 2005: mean=4.4 [scale 1 to 5], n=224). When 2004 course participants were surveyed during the last month of their internship, 84%“agree” or “strongly agree” with the statement: “The teaching to teach course helped prepare me for my role as a teacher during internship” (2005: mean 4.2 [scale 1 to 5], n=45, response rate 60%). A course preparing fourth‐year students to teach during internship is both feasible and reproducible, with a minimal commitment of faculty and resident time. Participants identify it as an important addition to their education and as useful during internship.