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Selected AbstractsCognitive Impairment Improves the Predictive Validity of the Phenotype of Frailty for Adverse Health Outcomes: The Three-City StudyJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 3 2009José Alberto Ávila-Funes MD OBJECTIVES: To determine whether adding cognitive impairment to frailty improves its predictive validity for adverse health outcomes. DESIGN: Four-year longitudinal study. SETTING: The French Three-City Study. PARTICIPANTS: Six thousand thirty community-dwelling persons aged 65 to 95. MEASUREMENTS: Frailty was defined as having at least three of the following criteria: weight loss, weakness, exhaustion, slowness, and low physical activity. Subjects meeting one or two criteria were prefrail and those meeting none as nonfrail. The lowest quartile in the Mini-Mental State Examination (MMSE) and the Isaacs Set Test (IST) was used to identify subjects with cognitive impairment. The predictive validity of frailty for incident disability, hospitalization, dementia, and death was calculated first for frailty subgroups and then rerun after stratification according to the presence or absence of cognitive impairment. RESULTS: Four hundred twenty-one individuals (7%) met frailty criteria. Cognitive impairment was present in 10%, 12%, and 22% of the nonfrail, prefrail, and frail subjects, respectively. Those classified as frail scored lower on the MMSE and IST than those classified as prefrail and nonfrail. After adjustment, frail persons with cognitive impairment were significantly more likely to develop disability in activities of daily living (ADLs) and instrumental ADLs over the following 4 years. The risk of incident mobility disability and hospitalization was marginally greater. Incident dementia was greater in the groups with cognitive impairment irrespective of their frailty status. Conversely, frailty was not a significant predictor of mortality. CONCLUSION: Cognitive impairment improves the predictive validity of the operational definition of frailty, because it increases the risk of adverse health outcomes in this particular subgroup of the elderly population. [source] A novel FIP1L1-PDGFRA mutant destabilizing the inactive conformation of the kinase domain in chronic eosinophilic leukemia/hypereosinophilic syndromeALLERGY, Issue 6 2009S. Salemi Background:, The Fip1-like-1,platelet-derived growth factor receptor alpha (FIP1L1-PDGFRA) gene fusion is a common cause of chronic eosinophilic leukemia (CEL)/hypereosinophilic syndrome (HES), and patients suffering from this particular subgroup of CEL/HES respond to low-dose imatinib therapy. However, some patients may develop imatinib resistance because of an acquired T674I mutation, which is believed to prevent drug binding through steric hindrance. Methods:, In an imatinib resistant FIP1L1-PDGFRA positive patient, we analyzed the molecular structure of the fusion gene and analyzed the effect of several kinase inhibitors on FIP1L1-PDGFRA-mediated proliferative responses in vitro. Results:, Sequencing of the FIP1L1-PDGFRA fusion gene revealed the occurrence of a S601P mutation, which is located within the nucleotide binding loop. In agreement with the clinical observations, imatinib did not inhibit the proliferation of S601P mutant FIP1L1-PDGFRA-transduced Ba/F3 cells. Moreover, sorafenib, which has been described to inhibit T674I mutant FIP1L1-PDGFRA, failed to block S601P mutant FIP1L1-PDGFRA. Structural modeling revealed that the newly identified S601P mutated form of PDGFRA destabilizes the inactive conformation of the kinase domain that is necessary to bind imatinib as well as sorafenib. Conclusions:, We identified a novel mutation in FIP1L1-PDGFRA resulting in both imatinib and sorafenib resistance. The identification of novel drug-resistant FIP1L1-PDGFRA variants may help to develop the next generation of target-directed compounds for CEL/HES and other leukemias. [source] Operated and unoperated cataract in AustraliaCLINICAL & EXPERIMENTAL OPHTHALMOLOGY, Issue 2 2000Catherine A McCarty PhD MPH ABSTRACT Purpose: To quantify the prevalence of cataract, the outcomes of cataract surgery and the factors related to unoperated cataract in Australia. Methods: Participants were recruited from the Visual Impairment Project: a cluster, stratified sample of more than 5000 Victorians aged 40 years and over. At examination sites interviews, clinical examinations and lens photography were performed. Cataract was defined in participants who had: had previous cataract surgery, cortical cataract greater than 4/16, nuclear greater than Wilmer standard 2, or posterior subcapsular greater than 1 mm 2. Results: The participant group comprised 3271 Melbourne residents, 403 Melbourne nursing home residents and 1473 rural residents. The weighted rate of any cataract in Victoria was 21.5%. The overall weighted rate of prior cataract surgery was 3.79%. Two hundred and forty-nine eyes had had prior cataract surgery. Of these 249 procedures, 49 (20%) were aphakic, 6 (2.4%) had anterior chamber intraocular lenses and 194 (78%) had posterior chamber intraocular lenses. Two hundred and eleven of these operated eyes (85%) had best-corrected visual acuity of 6/12 or better, the legal requirement for a driver's license. Twenty-seven (11%) had visual acuity of less than 6/18 (moderate vision impairment). Complications of cataract surgery caused reduced vision in four of the 27 eyes (15%), or 1.9% of operated eyes. Three of these four eyes had undergone intracapsular cataract extraction and the fourth eye had an opaque posterior capsule. No one had bilateral vision impairment as a result of cataract surgery. Surprisingly, no particular demographic factors (such as age, gender, rural residence, occupation, employment status, health insurance status, ethnicity) were related to the presence of unoperated cataract. Conclusions: Although the overall prevalence of cataract is quite high, no particular subgroup is systematically under-serviced in terms of cataract surgery. Overall, the results of cataract surgery are very good, with the majority of eyes achieving driving vision following cataract extraction. [source] Non-medical use of prescription stimulants among US college students: prevalence and correlates from a national surveyADDICTION, Issue 1 2005Sean Esteban McCabe ABSTRACT Aims To examine the prevalence rates and correlates of non-medical use of prescription stimulants (Ritalin, Dexedrine or Adderall) among US college students in terms of student and college characteristics. Design A self-administered mail survey. Setting One hundred and nineteen nationally representative 4-year colleges in the United States. Participants A representative sample of 10 904 randomly selected college students in 2001. Measurements Self-reports of non-medical use of prescription stimulants and other substance use behaviors. Findings The life-time prevalence of non-medical prescription stimulant use was 6.9%, past year prevalence was 4.1% and past month prevalence was 2.1%. Past year rates of non-medical use ranged from zero to 25% at individual colleges. Multivariate regression analyses indicated non-medical use was higher among college students who were male, white, members of fraternities and sororities and earned lower grade point averages. Rates were higher at colleges located in the north-eastern region of the US and colleges with more competitive admission standards. Non-medical prescription stimulant users were more likely to report use of alcohol, cigarettes, marijuana, ecstasy, cocaine and other risky behaviors. Conclusions The findings of the present study provide evidence that non-medical use of prescription stimulants is more prevalent among particular subgroups of US college students and types of colleges. The non-medical use of prescription stimulants represents a high-risk behavior that should be monitored further and intervention efforts are needed to curb this form of drug use. [source] Estimating the Intensity of a Spatial Point Process from Locations Coarsened by Incomplete GeocodingBIOMETRICS, Issue 1 2008Dale L. Zimmerman Summary The estimation of spatial intensity is an important inference problem in spatial epidemiologic studies. A standard data assimilation component of these studies is the assignment of a geocode, that is, point-level spatial coordinates, to the address of each subject in the study population. Unfortunately, when geocoding is performed by the standard automated method of street-segment matching to a georeferenced road file and subsequent interpolation, it is rarely completely successful. Typically, 10,30% of the addresses in the study population, and even higher percentages in particular subgroups, fail to geocode, potentially leading to a selection bias, called geographic bias, and an inefficient analysis. Missing-data methods could be considered for analyzing such data; however, because there is almost always some geographic information coarser than a point (e.g., a Zip code) observed for the addresses that fail to geocode, a coarsened-data analysis is more appropriate. This article develops methodology for estimating spatial intensity from coarsened geocoded data. Both nonparametric (kernel smoothing) and likelihood-based estimation procedures are considered. Substantial improvements in the estimation quality of coarsened-data analyses relative to analyses of only the observations that geocode are demonstrated via simulation and an example from a rural health study in Iowa. [source] |