http://hdl.handle.net/2144/1019 2013-05-23T02:19:07Z 2013-05-23T02:19:07Z Desikan, Rahul S. Sabuncu, Mert R. Schmansky, Nicholas J. Reuter, Martin Cabral, Howard J. Hess, Christopher P. Weiner, Michael W. Biffi, Alessandro Anderson, Christopher D. Rosand, Jonathan Salat, David H. Kemper, Thomas L. Dale, Anders M. Sperling, Reisa A. Fischl, Bruce http://hdl.handle.net/2144/3109 2012-01-12T07:00:34Z 2010-09-23T00:00:00Z

Selective Disruption of the Cerebral Neocortex in Alzheimer's Disease Desikan, Rahul S.; Sabuncu, Mert R.; Schmansky, Nicholas J.; Reuter, Martin; Cabral, Howard J.; Hess, Christopher P.; Weiner, Michael W.; Biffi, Alessandro; Anderson, Christopher D.; Rosand, Jonathan; Salat, David H.; Kemper, Thomas L.; Dale, Anders M.; Sperling, Reisa A.; Fischl, Bruce BACKGROUND. Alzheimer's disease (AD) and its transitional state mild cognitive impairment (MCI) are characterized by amyloid plaque and tau neurofibrillary tangle (NFT) deposition within the cerebral neocortex and neuronal loss within the hippocampal formation. However, the precise relationship between pathologic changes in neocortical regions and hippocampal atrophy is largely unknown. METHODOLOGY/PRINCIPAL FINDINGS. In this study, combining structural MRI scans and automated image analysis tools with reduced cerebrospinal fluid (CSF) Aß levels, a surrogate for intra-cranial amyloid plaques and elevated CSF phosphorylated tau (p-tau) levels, a surrogate for neocortical NFTs, we examined the relationship between the presence of Alzheimer's pathology, gray matter thickness of select neocortical regions, and hippocampal volume in cognitively normal older participants and individuals with MCI and AD (n=724). Amongst all 3 groups, only select heteromodal cortical regions significantly correlated with hippocampal volume. Amongst MCI and AD individuals, gray matter thickness of the entorhinal cortex and inferior temporal gyrus significantly predicted longitudinal hippocampal volume loss in both amyloid positive and p-tau positive individuals. Amongst cognitively normal older adults, thinning only within the medial portion of the orbital frontal cortex significantly differentiated amyloid positive from amyloid negative individuals whereas thinning only within the entorhinal cortex significantly discriminated p-tau positive from p-tau negative individuals. CONCLUSIONS/SIGNIFICANCE. Cortical Aß and tau pathology affects gray matter thinning within select neocortical regions and potentially contributes to downstream hippocampal degeneration. Neocortical Alzheimer's pathology is evident even amongst older asymptomatic individuals suggesting the existence of a preclinical phase of dementia.

2010-09-23T00:00:00Z Losina, Elena Bassett, Ingrid V. Giddy, Janet Chetty, Senica Regan, Susan Walensky, Rochelle P. Ross, Douglas Scott, Callie A. Uhler, Lauren M. Katz, Jeffrey N. Holst, Helga Freedberg, Kenneth A. http://hdl.handle.net/2144/3107 2012-01-13T07:00:28Z 2010-03-04T00:00:00Z

The "ART" of Linkage: Pre-Treatment Loss to Care after HIV Diagnosis at Two PEPFAR Sites in Durban, South Africa Losina, Elena; Bassett, Ingrid V.; Giddy, Janet; Chetty, Senica; Regan, Susan; Walensky, Rochelle P.; Ross, Douglas; Scott, Callie A.; Uhler, Lauren M.; Katz, Jeffrey N.; Holst, Helga; Freedberg, Kenneth A. BACKGROUND. Although loss to follow-up after antiretroviral therapy (ART) initiation is increasingly recognized, little is known about pre-treatment losses to care (PTLC) after an initial positive HIV test. Our objective was to determine PTLC in newly identified HIV-infected individuals in South Africa. METHODOLOGY/PRINCIPAL FINDINGS. We assembled the South African Test, Identify and Link (STIAL) Cohort of persons presenting for HIV testing at two sites offering HIV and CD4 count testing and HIV care in Durban, South Africa. We defined PTLC as failure to have a CD4 count within 8 weeks of HIV diagnosis. We performed multivariate analysis to identify factors associated with PTLC. From November 2006 to May 2007, of 712 persons who underwent HIV testing and received their test result, 454 (64%) were HIV-positive. Of those, 206 (45%) had PTLC. Infected patients were significantly more likely to have PTLC if they lived =10 kilometers from the testing center (RR=1.37; 95% CI: 1.11-1.71), had a history of tuberculosis treatment (RR=1.26; 95% CI: 1.00-1.58), or were referred for testing by a health care provider rather than self-referred (RR=1.61; 95% CI: 1.22-2.13). Patients with one, two or three of these risks for PTLC were 1.88, 2.50 and 3.84 times more likely to have PTLC compared to those with no risk factors. CONCLUSIONS/SIGNIFICANCE. Nearly half of HIV-infected persons at two high prevalence sites in Durban, South Africa, failed to have CD4 counts following HIV diagnosis. These high rates of pre-treatment loss to care highlight the urgent need to improve rates of linkage to HIV care after an initial positive HIV test.

2010-03-04T00:00:00Z Rydzak, Chara E. Cotich, Kara L. Sax, Paul E. Hsu, Heather E. Wang, Bingxia Losina, Elena Freedberg, Kenneth A. Weinstein, Milton C. Goldie, Sue J. http://hdl.handle.net/2144/3108 2012-01-12T07:00:34Z 2010-09-09T00:00:00Z

Assessing the Performance of a Computer-Based Policy Model of HIV and AIDS Rydzak, Chara E.; Cotich, Kara L.; Sax, Paul E.; Hsu, Heather E.; Wang, Bingxia; Losina, Elena; Freedberg, Kenneth A.; Weinstein, Milton C.; Goldie, Sue J. BACKGROUND. Model-based analyses, conducted within a decision analytic framework, provide a systematic way to combine information about the natural history of disease and effectiveness of clinical management strategies with demographic and epidemiological characteristics of the population. Among the challenges with disease-specific modeling include the need to identify influential assumptions and to assess the face validity and internal consistency of the model. METHODS AND FINDINGS. We describe a series of exercises involved in adapting a computer-based simulation model of HIV disease to the Women's Interagency HIV Study (WIHS) cohort and assess model performance as we re-parameterized the model to address policy questions in the U.S. relevant to HIV-infected women using data from the WIHS. Empiric calibration targets included 24-month survival curves stratified by treatment status and CD4 cell count. The most influential assumptions in untreated women included chronic HIV-associated mortality following an opportunistic infection, and in treated women, the 'clinical effectiveness' of HAART and the ability of HAART to prevent HIV complications independent of virologic suppression. Good-fitting parameter sets required reductions in the clinical effectiveness of 1st and 2nd line HAART and improvements in 3rd and 4th line regimens. Projected rates of treatment regimen switching using the calibrated cohort-specific model closely approximated independent analyses published using data from the WIHS. CONCLUSIONS. The model demonstrated good internal consistency and face validity, and supported cohort heterogeneities that have been reported in the literature. Iterative assessment of model performance can provide information about the relative influence of uncertain assumptions and provide insight into heterogeneities within and between cohorts. Description of calibration exercises can enhance the transparency of disease-specific models.

2010-09-09T00:00:00Z Reichmann, William M. Losina, Elena Seage, George R. Arbelaez, Christian Safren, Steven A. Katz, Jeffrey N. Hetland, Adam Walensky, Rochelle P. http://hdl.handle.net/2144/3104 2012-01-12T07:00:23Z 2010-01-15T00:00:00Z

Does Modality of Survey Administration Impact Data Quality: Audio Computer Assisted Self Interview (ACASI) Versus Self-Administered Pen and Paper? Reichmann, William M.; Losina, Elena; Seage, George R.; Arbelaez, Christian; Safren, Steven A.; Katz, Jeffrey N.; Hetland, Adam; Walensky, Rochelle P. BACKGROUND. In the context of a randomized controlled trial (RCT) on HIV testing in the emergency department (ED) setting, we evaluated preferences for survey modality and data quality arising from each modality. METHODS. Enrolled participants were offered the choice of answering a survey via audio computer assisted self-interview (ACASI) or pen and paper self-administered questionnaire (SAQ). We evaluated factors influencing choice of survey modality. We defined unusable data for a particular survey domain as answering fewer than 75% of the questions in the domain. We then compared ACASI and SAQ with respect to unusable data for domains that address sensitive topics. RESULTS. Of 758 enrolled ED patients, 218 (29%) chose ACASI, 343 chose SAQ (45%) and 197 (26%) opted not to complete either. Results of the log-binomial regression indicated that older (RR=1.08 per decade) and less educated participants (RR=1.25) were more likely to choose SAQ over ACASI. ACASI yielded substantially less unusable data than SAQ. CONCLUSIONS. In the ED setting there may be a tradeoff between increased participation with SAQ versus better data quality with ACASI. Future studies of novel approaches to maximize the use of ACASI in the ED setting are needed.

2010-01-15T00:00:00Z