1,612 results on '"Clifford, David"'
Search Results
2. Biopsychosocial phenotypes in people with HIV in the CHARTER cohort.
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Tang, Bin, Ellis, Ronald, Vaida, Florin, Umlauf, Anya, Franklin, Donald, Dastgheyb, Raha, Rubin, Leah, Riggs, Patricia, Iudicello, Jennifer, Clifford, David, Moore, David, Heaton, Robert, and Letendre, Scott
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HIV ,cluster analysis ,cognition ,daily functioning ,depression - Abstract
Neuropsychiatric complications such as neurocognitive impairment and depression are common in people with HIV despite viral suppression on antiretroviral therapy, but these conditions are heterogeneous in their clinical presentations and associated disability. Identifying novel biopsychosocial phenotypes that account for neurocognitive performance and depressive and functional symptoms will better reflect the complexities encountered in clinical practice and may have pathological and therapeutic implications. We classified 1580 people with HIV based on 17 features, including 7 cognitive domains, 4 subscales of the Beck depression inventory-II, 5 components of the patients assessment of own functioning inventory, and dependence in instrumental and basic activities of daily living. A two-stage clustering procedure consisting of dimension reduction with self-organizing maps and Mahalanobis distance-based k-means clustering algorithms was applied to cross-sectional data. Baseline demographic and clinical characteristics were compared between the phenotypes, and their prediction on the biopsychosocial phenotypes was evaluated using multinomial logistic regression. Four distinct phenotypes were identified. Participants in Phenotype 1 overall did well in all domains. Phenotype 2 had mild-to-moderate depressive symptoms and the most substance use disorders. Phenotype 3 had mild-to-moderate cognitive impairment, moderate depressive symptoms, and the worst daily functioning; they also had the highest proportion of females and non-HIV conditions that could affect cognition. Phenotype 4 had mild-to-moderate cognitive impairment but with relatively good mood, and daily functioning. Multivariable analysis showed that demographic characteristics, medical conditions, lifetime cocaine use disorder, triglycerides, and non-antiretroviral therapy medications were important variables associated with biopsychosocial phenotype. We found complex, multidimensional biopsychosocial profiles in people with HIV that were associated with different risk patterns. Future longitudinal work should determine the stability of these phenotypes, assess factors that influence transitions from one phenotype to another, and characterize their biological associations.
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- 2024
3. Higher Levels of Cerebrospinal Fluid and Plasma Neurofilament Light in Human Immunodeficiency Virus-Associated Distal Sensory Polyneuropathy
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Ellis, Ronald J, Chenna, Ahmed, Lie, Yolanda, Curanovic, Dusica, Winslow, John, Tang, Bin, Marra, Christina M, Rubin, Leah H, Clifford, David B, McCutchan, J Allen, Gelman, Benjamin B, Robinson-Papp, Jessica, Petropoulos, Christos J, and Letendre, Scott L
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Medical Microbiology ,Biomedical and Clinical Sciences ,Neurosciences ,Clinical Research ,HIV/AIDS ,Infection ,Humans ,Female ,Middle Aged ,Aged ,Male ,HIV ,Intermediate Filaments ,HIV Infections ,Biomarkers ,Polyneuropathies ,polyneuropathy ,biomarker ,cerebrospinal fluid ,neurofilament light ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Clinical sciences - Abstract
BackgroundNeurofilament light (NFL) chain concentrations, reflecting axonal damage, are seen in several polyneuropathies but have not been studied in human immunodeficiency virus (HIV) distal sensory polyneuropathy (DSP). We evaluated NFL in cerebrospinal fluid (CSF) and plasma in relation to DSP in people with HIV (PWH) from 2 independent cohorts and in people without HIV (PWoH).MethodsCohort 1 consisted of PWH from the CHARTER Study. Cohort 2 consisted of PWH and PWoH from the HIV Neurobehavioral Research Center (HNRC). We evaluated DSP signs and symptoms in both cohorts. Immunoassays measured NFL in CSF for all and for plasma as well in Cohort 2.ResultsCohort 1 consisted of 111 PWH, mean ± SD age 56.8 ± 8.32 years, 15.3% female, 38.7% Black, 49.6% White, current CD4+ T-cells (median, interquartile range [IQR]) 532/µL (295, 785), 83.5% with plasma HIV RNA ≤50 copies/mL. Cohort 2 consisted of 233 PWH of similar demographics to PWH in Cohort 1 but also 51 PWoH, together age 58.4 ± 6.68 years, 41.2% female, 18.0% Black, Hispanic, non-Hispanic White 52.0%, 6.00% White. In both cohorts of PWH, CSF and plasma NFL were significantly higher in both PWH with DSP signs. Findings were similar, albeit not significant, for PWoH. The observed relationships were not explained by confounds.ConclusionsBoth plasma and CSF NFL were elevated in PWH and PWoH with DSP. The convergence of our findings with others demonstrates that NFL is a reliable biomarker reflecting peripheral nerve injury. Biomarkers such as NFL might provide, validate, and optimize clinical trials of neuroregenerative strategies in HIV DSP.
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- 2023
4. Twelve-year neurocognitive decline in HIV is associated with comorbidities, not age: a CHARTER study
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Heaton, Robert K, Ellis, Ronald J, Tang, Bin, Marra, Christina M, Rubin, Leah H, Clifford, David B, McCutchan, J Allen, Gelman, Benjamin B, Morgello, Susan, Franklin, Donald R, and Letendre, Scott L
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Biomedical and Clinical Sciences ,Clinical Sciences ,HIV/AIDS ,Sexually Transmitted Infections ,Infectious Diseases ,Neurodegenerative ,Brain Disorders ,Neurosciences ,Mental Health ,Aging ,Behavioral and Social Science ,7.1 Individual care needs ,Evaluation of treatments and therapeutic interventions ,Management of diseases and conditions ,6.1 Pharmaceuticals ,Mental health ,Good Health and Well Being ,Humans ,HIV Infections ,Comorbidity ,HIV ,neurologic complications ,cognition ,brain ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Neurology & Neurosurgery ,Biomedical and clinical sciences ,Health sciences ,Psychology - Abstract
Modern antiretroviral therapy (ART) has increased longevity of people with HIV and shifted the age distribution of the HIV pandemic upward toward that of the general population. This positive development has also led to concerns about premature and/or accelerated neurocognitive and physical ageing due to the combined effects of chronic HIV, accumulating comorbidities, adverse effects or possible toxicities of ART and biological ageing. Here we present results of comprehensive assessments over 12 years of 402 people with HIV in the CNS HIV ART Effects Research (CHARTER) programme, who at follow-up were composed of younger (
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- 2023
5. Elevated Plasma Protein Carbonyl Concentration Is Associated with More Abnormal White Matter in People with HIV
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Riggs, Patricia K, Anderson, Albert M, Tang, Bin, Rubin, Leah H, Morgello, Susan, Marra, Christina M, Gelman, Benjamin B, Clifford, David B, Franklin, Donald, Heaton, Robert K, Ellis, Ronald J, Fennema-Notestine, Christine, and Letendre, Scott L
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Microbiology ,Biological Sciences ,Prevention ,Infectious Diseases ,Neurosciences ,HIV/AIDS ,Neurological ,Male ,Humans ,Middle Aged ,Female ,White Matter ,Protein Carbonylation ,Cross-Sectional Studies ,HIV Infections ,Blood Proteins ,Inflammation ,HIV ,oxidative stress ,brain ,magnetic resonance imaging ,white matter - Abstract
Structural brain abnormalities, including those in white matter (WM), remain common in people with HIV (PWH). Their pathogenesis is uncertain and may reflect multiple etiologies. Oxidative stress is associated with inflammation, HIV, and its comorbidities. The post-translational carbonylation of proteins results from oxidative stress, and circulating protein carbonyls may reflect this. In this cross-sectional analysis, we evaluated the associations between protein carbonyls and a panel of soluble biomarkers of neuronal injury and inflammation in plasma (N = 45) and cerebrospinal fluid (CSF, n = 32) with structural brain MRI. The volume of abnormal WM was normalized for the total WM volume (nAWM). In this multisite project, all regression models were adjusted for the scanner. The candidate covariates included demographics, HIV disease characteristics, and comorbidities. Participants were PWH on virally suppressive antiretroviral therapy (ART) and were mostly white (64.4%) men (88.9%), with a mean age of 56.8 years. In unadjusted analyses, more nAWM was associated with higher plasma protein carbonyls (p = 0.002) and higher CCL2 (p = 0.045). In the adjusted regression models for nAWM, the association with plasma protein carbonyls remained significant (FDR p = 0.018). Protein carbonyls in plasma may be a valuable biomarker of oxidative stress and its associated adverse health effects, including within the central nervous system. If confirmed, these findings would support the hypothesis that reducing oxidative stress could treat or prevent WM injury in PWH.
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- 2023
6. Increasing Neuroinflammation Relates to Increasing Neurodegeneration in People with HIV
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Tavasoli, Azin, Gelman, Benjamin B, Marra, Christina M, Clifford, David B, Iudicello, Jennifer E, Rubin, Leah H, Letendre, Scott L, Tang, Bin, and Ellis, Ronald J
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Microbiology ,Biological Sciences ,HIV/AIDS ,Infectious Diseases ,Inflammatory and immune system ,Humans ,HIV Infections ,Neopterin ,Neuroinflammatory Diseases ,Biomarkers ,Inflammation ,HIV ,viral suppression ,neuroinflammation ,neurodegeneration ,inflammatory biomarkers - Abstract
BackgroundHIV infection causes neuroinflammation and immune activation (NIIA) and systemic inflammation and immune activation (SIIA), which in turn drive neurodegeneration (ND). Cross-sectionally, higher levels of NIIA biomarkers correlate with increased biomarkers of ND. A more convincing confirmation would be a longitudinal demonstration.MethodsPWH in the US multisite CHARTER Aging project were assessed at a baseline visit and after 12 years using standardized evaluations. We measured a panel of 14 biomarkers of NIIA, SIIA, and ND in plasma and CSF at two time points and calculated changes from baseline to the 12-year visit. Factor analysis yielded simplified indices of NIIA, SIIA, and ND.ResultsThe CSF NIIA factor analysis yielded Factor1 loading on soluble tumor necrosis factor type-2 (sTNFR-II) and neopterin, and Factor2, loading on MCP1, soluble CD14, and IL-6. The SIIA factor analysis yielded Factor1 loading on CRP, D-dimer, and Neopterin; Factor2 loading on sTNFR-II. The ND analysis yielded Factor1 loading on Phosphorylated tau (p-tau) and Aβ42; Factor2 loading on NFL. NIIA Factor1, but not Factor2, correlated with increases in CSF NFL (r = 0.370, p = 0.0002).ConclusionsIncreases in NIIA and SIIA in PWH were associated with corresponding increases in ND, suggesting that reducing neuro/systemic inflammation might slow or reverse neurodegeneration.
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- 2023
7. Longitudinal head-to-head comparison of 11C-PiB and 18F-florbetapir PET in a Phase 2/3 clinical trial of anti-amyloid-β monoclonal antibodies in dominantly inherited Alzheimer’s disease
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Chen, Charles D., McCullough, Austin, Gordon, Brian, Joseph-Mathurin, Nelly, Flores, Shaney, McKay, Nicole S., Hobbs, Diana A., Hornbeck, Russ, Fagan, Anne M., Cruchaga, Carlos, Goate, Alison M., Perrin, Richard J., Wang, Guoqiao, Li, Yan, Shi, Xinyu, Xiong, Chengjie, Pontecorvo, Michael J., Klein, Gregory, Su, Yi, Klunk, William E., Jack, Clifford, Koeppe, Robert, Snider, B. Joy, Berman, Sarah B., Roberson, Erik D., Brosch, Jared, Surti, Ghulam, Jiménez-Velázquez, Ivonne Z., Galasko, Douglas, Honig, Lawrence S., Brooks, William S., Clarnette, Roger, Wallon, David, Dubois, Bruno, Pariente, Jérémie, Pasquier, Florence, Sanchez-Valle, Raquel, Shcherbinin, Sergey, Higgins, Ixavier, Tunali, Ilke, Masters, Colin L., van Dyck, Christopher H., Masellis, Mario, Hsiung, Robin, Gauthier, Serge, Salloway, Steve, Clifford, David B., Mills, Susan, Supnet-Bell, Charlene, McDade, Eric, Bateman, Randall J., and Benzinger, Tammie L. S.
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- 2023
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8. Neuropathic pain correlates with worsening cognition in people with human immunodeficiency virus
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Ellis, Ronald J, Sacktor, Ned, Clifford, David B, Marra, Christina M, Collier, Ann C, Gelman, Benjamin, Robinson-Papp, Jessica, Letendre, Scott L, Heaton, Robert K, and Group, for the CNS Antiretroviral Therapy Effects Research Study
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Biomedical and Clinical Sciences ,Neurosciences ,Clinical Sciences ,Behavioral and Social Science ,Mental Health ,Neurodegenerative ,Chronic Pain ,Peripheral Neuropathy ,Infectious Diseases ,Pain Research ,Clinical Research ,HIV/AIDS ,6.1 Pharmaceuticals ,2.1 Biological and endogenous factors ,Aetiology ,Evaluation of treatments and therapeutic interventions ,Neurological ,Cognition ,Female ,HIV ,HIV Infections ,Humans ,Male ,Neuralgia ,Prospective Studies ,cognition ,biomarkers ,neurodegeneration ,cerebrospinal fluid ,CNS Antiretroviral Therapy Effects Research (CHARTER) Study Group ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Neurology & Neurosurgery ,Biomedical and clinical sciences ,Health sciences ,Psychology - Abstract
Neuropathic pain and cognitive impairment are among the HIV-related conditions that have most stubbornly resisted amelioration by virally suppressive antiretroviral therapy. Overlaps between the regional brain substrates and mechanisms of neuropathic pain and cognitive disorders are increasingly recognized, yet no studies have examined the longitudinal relationship between these two disorders. Participants in the prospective, observational CNS HIV AntiRetroviral Therapy Effects Research (CHARTER) cohort underwent standardized clinical evaluations for clinical examination findings of distal sensory polyneuropathy, reporting distal neuropathic pain and neurocognitive performance at study entry (baseline) and an average of 12 years later. Change in neuropathic pain and neuropathy status from baseline to follow-up was by self-report and repeat examination, and change in neurocognitive performance was assessed using a previously published summary regression-based change score. Relationships between incident or worsened neuropathic pain and neurocognitive change were evaluated using uni- and multivariable regressions, including age at baseline and other relevant covariates. Participants were 385 people with HIV, 91 (23.6%) females, mean ± standard deviation (SD) age at baseline 43.5 (7.81) years, ethnicity 44.9% African American, 10.6% Hispanic, 42.6% non-Hispanic white and 1.82% other. Baseline median (interquartile range) nadir CD4 was 175 (34 309) cells/µl and current CD4 was 454 (279 639). Incident or worsened distal neuropathic pain occurred in 98 (25.5%) over the follow-up period. People with HIV with incident or worsened distal neuropathic pain had significantly worsened neurocognitive performance at follow-up compared to those without incident or worsened distal neuropathic pain (summary regression-based change score mean ± SD -0.408 ± 0.700 versus -0.228 ± 0.613; P = 0.0158). This effect remained significant when considering viral suppression on antiretroviral therapy, incident diabetes and other covariates as predictors. Overall neurocognitive change related to neuropathic pain was driven primarily by changes in the domains of executive function and speed of information processing. Those with incident distal neuropathy signs did not have neurocognitive worsening, nor did individuals who used opioid analgesics or other pain-modulating drugs such as amitriptyline. Worsened neurocognitive performance in people with HIV was associated with worsened neuropathic pain but not with changes in physical signs of neuropathy, and this was not attributable to therapies for pain or depression or to differences in viral suppression. This finding implies that incident or worsened pain may signal increased risk for neurocognitive impairment, and deserves more investigation, particularly if better pain management might stabilize or improve neurocognitive performance.
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- 2022
9. Ethnic/Racial Disparities in Longitudinal Neurocognitive Decline in People With HIV
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Watson, Caitlin Wei-Ming, Kamalyan, Lily, Tang, Bin, Hussain, Mariam A, Cherner, Mariana, Mindt, Monica Rivera, Byrd, Desiree A, Franklin, Donald R, Collier, Ann C, Clifford, David B, Gelman, Benjamin, Morgello, Susan, McCutchan, John Allen, Ellis, Ronald J, Grant, Igor, Heaton, Robert K, Marquine, María J, and Group, for the CHARTER
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Biomedical and Clinical Sciences ,Public Health ,Health Sciences ,Infectious Diseases ,Behavioral and Social Science ,HIV/AIDS ,Prevention ,Mental Health ,Clinical Research ,Comorbidity ,Ethnicity ,HIV Infections ,Healthcare Disparities ,Hispanic or Latino ,Humans ,Proportional Hazards Models ,Hispanic Americans ,African Americans ,cognitive disorders ,health status disparities ,CHARTER Group ,Clinical Sciences ,Public Health and Health Services ,Virology ,Clinical sciences ,Epidemiology ,Public health - Abstract
BackgroundTo examine longitudinal neurocognitive decline among Latino, non-Latino Black, and non-Latino White people with HIV (PWH) and factors that may explain ethnic/racial disparities in neurocognitive decline.MethodsFour hundred ninety nine PWH (13.8% Latino, 42.7% Black, 43.5% White; baseline age: M = 43.5) from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study completed neurocognitive, neuromedical, and laboratory assessments every 6-12 months with up to 5 years of follow-up. Longitudinal neurocognitive change was determined via published regression-based norms. Survival analyses investigated the relationship between ethnicity/race and neurocognitive change, and baseline and time-dependent variables that may explain ethnic/racial disparities in neurocognitive decline, including socio-demographic, HIV-disease, medical, psychiatric, and substance use characteristics.ResultsIn Cox proportional hazard models, hazard ratios for neurocognitive decline were increased for Latino compared with White PWH (HR = 2.25, 95% CI = 1.35 to 3.73, P = 0.002), and Latino compared with Black PWH (HR = 1.86, 95% CI = 1.14 to 3.04, P = 0.013), with no significant differences between Black and White PWH (P = 0.40). Comorbidities, including cardiometabolic factors and more severe neurocognitive comorbidity classification, accounted for 33.6% of the excess hazard for Latino compared with White PWH, decreasing the hazard ratio associated with Latino ethnicity (HR = 1.83, 95% CI = 1.06 to 3.16, P = 0.03), but did not fully account for elevated risk of decline.ConclusionsLatino PWH may be at higher risk of early neurocognitive decline compared with Black and White PWH. Comorbidities accounted for some, but not all, of this increased risk among Latino PWH. Future research examining institutional, sociocultural, and biomedical factors, including structural discrimination and age-related biomarkers, may further explain the observed disparities.
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- 2022
10. Higher buccal mitochondrial DNA and mitochondrial common deletion number are associated with markers of neurodegeneration and inflammation in cerebrospinal fluid
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Solanky, Dipesh, Fields, Jerel A, Iudicello, Jennifer E, Ellis, Ronald J, Franklin, Donald, Clifford, David B, Gelman, Benjamin B, Marra, Christina M, Morgello, Susan, Rubin, Leah H, Grant, Igor, Heaton, Robert K, Letendre, Scott L, and Mehta, Sanjay R
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Biomedical and Clinical Sciences ,Immunology ,Neurodegenerative ,Neurosciences ,Aging ,HIV/AIDS ,Prevention ,Clinical Research ,Infectious Diseases ,Genetics ,Aetiology ,2.1 Biological and endogenous factors ,Infection ,Good Health and Well Being ,Adult ,Aging ,Premature ,Biomarkers ,DNA ,Mitochondrial ,Female ,HIV Infections ,Humans ,Inflammation ,Male ,Middle Aged ,Mitochondrial DNA ,Amyloid ,Neuroinflammation ,Neurodegeneration ,HIV ,Clinical Sciences ,Medical Microbiology ,Virology ,Clinical sciences ,Medical microbiology - Abstract
Human immunodeficiency virus (HIV) infection is potentially associated with premature aging, but demonstrating this is difficult due to a lack of reliable biomarkers. The mitochondrial (mt) DNA "common deletion" mutation (mtCDM) is a 4977-bp deletion associated with aging and neurodegenerative diseases. We examined how mtDNA and mtCDM correlate with markers of neurodegeneration and inflammation in people with and without HIV (PWH and PWOH). Data from 149 adults were combined from two projects involving PWH (n = 124) and PWOH (n = 25). We measured buccal mtDNA and mtCDM by digital droplet PCR and compared them to disease and demographic characteristics and soluble biomarkers in cerebrospinal fluid (CSF) and blood measured by immunoassay. Participants had a median age of 52 years, with 53% white and 81% men. Median mtDNA level was 1,332 copies/cell (IQR 1,201-1,493) and median mtCDM level was 0.36 copies × 102/cell (IQR 0.31-0.42); both were higher in PWH. In the best model adjusting for HIV status and demographics, higher mtDNA levels were associated with higher CSF amyloid-β 1-42 and 8-hydroxy-2'-deoxyguanosine and higher mtCDM levels were associated with higher plasma soluble tumor necrosis factor receptor II. The differences in mtDNA markers between PWH and PWOH support potential premature aging in PWH. Our findings suggest mtDNA changes in oral tissues may reflect CNS processes, allowing the use of inexpensive and easily accessible buccal biospecimens as a screening tool for CSF inflammation and neurodegeneration. Confirmatory and mechanistic studies on mt genome alterations by HIV and ART may identify interventions to prevent or treat neurodegenerative complications.
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- 2022
11. Semantically Robust Unpaired Image Translation for Data with Unmatched Semantics Statistics
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Jia, Zhiwei, Yuan, Bodi, Wang, Kangkang, Wu, Hong, Clifford, David, Yuan, Zhiqiang, and Su, Hao
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Computer Science - Computer Vision and Pattern Recognition - Abstract
Many applications of unpaired image-to-image translation require the input contents to be preserved semantically during translations. Unaware of the inherently unmatched semantics distributions between source and target domains, existing distribution matching methods (i.e., GAN-based) can give undesired solutions. In particular, although producing visually reasonable outputs, the learned models usually flip the semantics of the inputs. To tackle this without using extra supervision, we propose to enforce the translated outputs to be semantically invariant w.r.t. small perceptual variations of the inputs, a property we call "semantic robustness". By optimizing a robustness loss w.r.t. multi-scale feature space perturbations of the inputs, our method effectively reduces semantics flipping and produces translations that outperform existing methods both quantitatively and qualitatively., Comment: Accepted to ICCV 2021
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- 2020
12. Paresthesia Predicts Increased Risk of Distal Neuropathic Pain in Older People with HIV-Associated Sensory Polyneuropathy
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Diaz, Monica M, Keltner, John R, Simmons, Alan N, Franklin, Donald, Moore, Raeanne C, Clifford, David, Collier, Ann C, Gelman, Benjamin B, Marra, Christina, McCutchan, J Allen, Morgello, Susan, Sacktor, Ned, Best, Brookie, Notestine, Christine Fennema, Weibel, Sara Gianella, Grant, Igor, Marcotte, Thomas D, Vaida, Florin, Letendre, Scott, Heaton, Robert, and Ellis, Ronald J
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Biomedical and Clinical Sciences ,Clinical Sciences ,Sexually Transmitted Infections ,Chronic Pain ,HIV/AIDS ,Infectious Diseases ,Peripheral Neuropathy ,Neurodegenerative ,Pain Research ,Aging ,Neurosciences ,Aged ,Female ,HIV Infections ,Humans ,Longitudinal Studies ,Middle Aged ,Neuralgia ,Paresthesia ,Polyneuropathies ,Prospective Studies ,Quality of Life ,HIV ,Neuropathy ,Pain ,CHARTER Study ,Pharmacology and Pharmaceutical Sciences ,Public Health and Health Services ,Anesthesiology ,Clinical sciences ,Health services and systems ,Clinical and health psychology - Abstract
ObjectiveDistal sensory polyneuropathy (DSP) is a disabling consequence of human immunodeficiency virus (HIV), leading to poor quality of life and more frequent falls in older age. Neuropathic pain and paresthesia are prevalent symptoms; however, there are currently no known curative treatments and the longitudinal course of pain in HIV-associated DSP is poorly characterized.MethodsThis was a prospective longitudinal study of 265 people with HIV (PWH) enrolled in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) study with baseline and 12-year follow-up evaluations. Since pain and paresthesia are highly correlated, statistical decomposition was used to separate the two symptoms at baseline. Multivariable logistic regression analyses of decomposed variables were used to determine the effects of neuropathy symptoms at baseline on presence and worsening of distal neuropathic pain at 12-year follow-up, adjusted for covariates.ResultsMean age was 56 ± 8 years, and 21% were female at follow-up. Nearly the entire cohort (96%) was on antiretroviral therapy (ART), and 82% had suppressed (≤50 copies/mL) plasma viral loads at follow-up. Of those with pain at follow-up (n = 100), 23% had paresthesia at the initial visit. Decomposed paresthesia at baseline increased the risk of pain at follow-up (odds ratio [OR] 1.56; 95% confidence interval [CI] 1.18, 2.07), and decomposed pain at baseline predicted a higher frequency of pain at follow-up (OR 1.96 [95% CI 1.51, 2.58]).ConclusionsParesthesias are a clinically significant predictor of incident pain at follow-up among aging PWH with DSP. Development of new therapies to encourage neuroregeneration might take advantage of this finding to choose individuals likely to benefit from treatment preventing incident pain.
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- 2021
13. Large Mitochondrial DNA Deletions in HIV Sensory Neuropathy
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Roda, Ricardo H, Bargiela, David, Chen, Weiran, Perry, Ken, Ellis, Ronald J, Clifford, David B, Bharti, Ajay, Kallianpur, Asha R, Oliveira, Michelli F, Diaz, Monica M, Rubin, Leah H, Gavegnano, Christina, McArthur, Justin C, Hoke, Ahmet, and Polydefkis, Michael
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Biomedical and Clinical Sciences ,Clinical Sciences ,Genetics ,Neurosciences ,Clinical Research ,Chronic Pain ,Neurodegenerative ,Infectious Diseases ,HIV/AIDS ,Pain Research ,Peripheral Neuropathy ,Adult ,DNA ,Mitochondrial ,Female ,HIV Infections ,Humans ,Male ,Middle Aged ,Mutation ,Peripheral Nervous System Diseases ,Peroneal Neuropathies ,Retrospective Studies ,Skin ,Sural Nerve ,Cognitive Sciences ,Neurology & Neurosurgery ,Clinical sciences - Abstract
ObjectiveThe primary objective of this study was to evaluate the correlation of large mitochondrial DNA (mtDNA) deletions in skin samples of people with HIV (PWH) with measures of neuropathy and prior exposure to therapy. We hypothesized that deletions would be associated with neuropathy. As secondary objectives, we determined the correlation of deletion burden with demographic data and neuropathy measures.MethodsIn this retrospective cohort study, we measured the accumulation of large mtDNA deletions in skin biopsies from PWH recruited as part of the AIDS Clinical Trials Group (ACTG). Our cohort includes individuals with and without sensory neuropathy, as well as individuals with normal or abnormal skin biopsies. Skin biopsies, sural and peroneal nerve conduction studies, total neuropathy score, and deletion burden scores were measured, along with baseline demographic data such as age, CD4+ cell count, viral counts, and prior nucleoside reverse transcriptase inhibitor exposures.ResultsSixty-seven PWH were enrolled in the study. The mean age of the cohort (n = 67) was 44 years (SD 6.8, range 32-65 years), and 9 participants were female. The mean CD4+ T-cell count was 168 cells/mm3 (SD 97 cells/mm3, range 1-416 cells/mm3) and mean viral load was 51,129 copies/mL (SD 114,586 copies/mL, range 147-657,775 copies/mL). We determined that there was a correlation between the total mtDNA deletion and intraepidermal nerve fiber density (IENFD) (r = -0.344, p = 0.04) and sural nerve amplitude (r = -0.359, p = 0.004).ConclusionsBoth IENFD and sural nerve amplitude statistically correlate with mitochondrial mutation burden in PWH, specifically in those with HIV-associated sensory neuropathy as assessed by skin biopsy.
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- 2021
14. Peripheral Inflammation and Depressed Mood Independently Predict Neurocognitive Worsening Over 12 Years
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Ellis, Ronald J, Heaton, Robert K, Tang, Bin, Collier, Ann C, Marra, Christina, Gelman, Benjamin B, Morgello, Susan, Clifford, David B, Sacktor, Ned, and Letendre, Scott L
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Clinical Sciences ,Neurosciences ,Neurology & Neurosurgery - Published
- 2021
15. Antiretroviral therapy intensification for HIV-associated neurocognitive disorder?
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Brew, Bruce J. and Clifford, David B.
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- 2023
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16. The place of charity in a public health service: Inequality and persistence in charitable support for NHS trusts in england
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Bowles, James, Clifford, David, and Mohan, John
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- 2023
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17. Higher levels of plasma inflammation biomarkers are associated with depressed mood and quality of life in aging, virally suppressed men, but not women, with HIV.
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Ellis, Ronald J, Letendre, Scott L, Atkinson, J Hampton, Clifford, David, Collier, Ann C, Gelman, Benjamin B, Marra, Christina, McCutchan, J Allen, Morgello, Susan, Sacktor, Ned, Tang, Bin, and Heaton, Robert K
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Depression ,HIV infection ,Inflammation ,Quality of life ,Sex differences ,Mental Health ,Clinical Research ,6.1 Pharmaceuticals ,Inflammatory and immune system - Abstract
Background and objectivesPeople with HIV (PWH) often suffer from depressive symptoms which have a deleterious impact on numerous domains including antiretroviral adherence and quality of life. In the general population, a treatment-resistant phenotype of depression is associated with systemic inflammation, which is of considerable importance as it responds favorably to anti-inflammatory medications. Aging PWH experience increasing inflammation. We sought to evaluate the impact of chronic inflammation in aging PWH on depressed mood.MethodsPWH were recruited at 6 U.S. academic medical centers. Depressed mood was assessed using the Beck Depression Inventory (BDI)-II. Inflammatory biomarkers measured at the 12-year follow-up visit in blood plasma using immunoassays were neopterin, sTNFRII, d-dimer, IL-6, CRP, MCP-1, sCD14 and sCD40L. Factor analyses with oblique Equamax rotation were employed to reduce the dimensionality of the biomarkers.ResultsParticipants were 78 PWH, 14 (17.9%) women, 40 (51.3%) non-White, mean age 55.3 (±SD 8.29), with a nadir and current CD4 of 134 (IQR 36, 204) and 567 (316, 797), respectively. 80.5% were virally suppressed. A factor analysis of the eight inflammatory biomarkers in plasma at the 12-year follow-up visit yielded 3 Factors, with Factor 1 loading on neopterin and sTNFRII, Factor 2 loading on d-dimer, IL-6 and CRP, and Factor 3 loading on sCD40L (MCP-1 and sCD14 did not appear in any of the factors). Univariate regressions of each factor vs BDI-II scores yielded significance only for Factor 2 (r = 0.295; p = 0.0083 (Bonferroni-adjusted p = 0.0261). Of the Factor 2 component biomarkers, BDI-II scores correlated significantly with d-dimer and IL-6, but not CRP. Women had worse BDI-II scores (p = 0.0127). In a logistic regression with sex and Factor 2, both variables were significant (sex p = 0.0246, Factor 2 p = 0.0168). The relationship between Factor 2 and BDI was significant for men (r = 0.348 [95% CI 0.111, 0.547]; p = 0.0049), but not women (r = 0.0580 95% CI -0.488, 0.571]; p = 0.844). Viral suppression was not significant in the multivariate model.ConclusionsSome PWH with depressed mood have elevated markers of inflammation in blood. Men showed this relationship, while women did not. Together with previous findings that an inflammatory depression phenotype responds to treatment with anti-inflammatory medications, our findings suggest that treatment with anti-inflammatory medications might benefit at least a subset of depressed PWH who have a high inflammatory biomarker profile, as well as poor response to antidepressant medications alone, and that the pathophysiology of depression in men and women with HIV may differ.
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- 2020
18. Predictors of worsening neuropathy and neuropathic pain after 12 years in people with HIV.
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Ellis, Ronald J, Diaz, Monica, Sacktor, Ned, Marra, Christina, Collier, Ann C, Clifford, David B, Calcutt, Nigel, Fields, Jerel A, Heaton, Robert K, Letendre, Scott L, and CNS Antiretroviral Therapy Effects Research (CHARTER) Study Group
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CNS Antiretroviral Therapy Effects Research (CHARTER) Study Group ,Humans ,HIV Infections ,Neuralgia ,Polyneuropathies ,Body Mass Index ,Activities of Daily Living ,Severity of Illness Index ,Incidence ,Prevalence ,Risk Factors ,Follow-Up Studies ,Quality of Life ,Adult ,Middle Aged ,Unemployment ,Female ,Male ,Protective Factors ,Chronic Pain ,Neurodegenerative ,Pain Research ,Prevention ,Neurosciences ,Peripheral Neuropathy ,Clinical Research ,HIV/AIDS ,Neurological ,Clinical Sciences - Abstract
ObjectiveDistal sensory polyneuropathy (DSP) and neuropathic pain are important clinical concerns in virally suppressed people with HIV. We determined how these conditions evolved, what factors influenced their evolution, and their clinical impact.MethodsAmbulatory, community-dwelling HIV seropositive individuals were recruited at six research centers. Clinical evaluations at baseline and 12 years later determined neuropathy signs and distal neuropathic pain (DNP). Additional assessments measured activities of daily living and quality of life (QOL). Factors potentially associated with DSP and DNP progression included disease severity, treatment, demographics, and co-morbidities. Adjusted odds ratios were calculated for follow-up neuropathy outcomes.ResultsOf 254 participants, 21.3% were women, 57.5% were non-white. Mean baseline age was 43.5 years. Polyneuropathy prevalence increased from 25.7% to 43.7%. Of 173 participants initially pain-free, 42 (24.3%) had incident neuropathic pain. Baseline risk factors for incident pain included unemployment (OR [95% CI], 5.86 [1.97, 17.4]) and higher baseline body mass index (BMI) (1.78 [1.03, 3.19] per 10-units). Participants with neuropathic pain at follow-up had significantly worse QOL and greater dependence in activities of daily living than those who remained pain-free.InterpretationHIV DSP and neuropathic pain increased in prevalence and severity over 12 years despite high rates of viral suppression. The high burden of neuropathy included disability and poor life quality. However, substantial numbers remained pain-free despite clear evidence of neuropathy on exam. Protective factors included being employed and having a lower BMI. Implications for clinical practice include promotion of lifestyle changes affecting reversible risk factors.
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- 2020
19. Seven-Year Experience From the National Institute of Neurological Disorders and Stroke-Supported Network for Excellence in Neuroscience Clinical Trials.
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Cudkowicz, Merit, Chase, Marianne, Coffey, Christopher, Ecklund, Dixie, Thornell, Brenda, Lungu, Codrin, Mahoney, Katy, Gutmann, Laurie, Shefner, Jeremy, Staley, Kevin, Bosch, Michael, Foster, Eric, Long, Jeffrey, Bayman, Emine, Torner, James, Yankey, Jon, Peters, Richard, Huff, Trevis, Conwit, Robin, Shinnar, Shlomo, Patch, Donna, Darras, Basil, Ellis, Audrey, Packer, Roger, Marder, Karen, Chiriboga, Claudia, Moran, Joyce, Nikolov, Blagovest, Factor, Stewart, Seeley, Carole, Greenberg, Steven, Amato, Anthony, DeGregorio, Sara, Simuni, Tanya, Ward, Tina, Kissel, John, Kolb, Stephen, Bartlett, Amy, Quinn, Joseph, Keith, Kellie, Levine, Steven, Gilles, Nadege, Coyle, Patricia, Lamb, Jessica, Wolfe, Gil, Crumlish, Annemarie, Mejico, Luis, Iqbal, Muhammad, Bowen, James, Tongco, Caryl, Nabors, Louis, Bashir, Khurram, Benge, Melanie, Canamar, Catherine, Glauser, Tracy, Woo, Daniel, Molloy, Angela, Clark, Peggy, Vollmer, Timothy, Stein, Alexander, Barohn, Richard, Dimachkie, Mazen, Le Pichon, Jean-Baptiste, Benatar, Michael, Steele, Julie, Wechsler, Lawrence, Clemens, Paula, Amity, Christine, Holloway, Robert, Annis, Christine, Goldberg, Mark, Andersen, Mariam, Iannaccone, Susan, Smith, A, Singleton, J, Doudova, Mariana, Haley, E, Quigg, Mark, Lowenhaupt, Stephanie, Malow, Beth, Adkins, Karen, Clifford, David, Teshome, Mengesha, Connolly, Noreen, Oskarsson, Björn, Dobkin, Bruce, McDonald, Craig, Henricson, Erik, and Henchcliffe, Claire
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Clinical Trials as Topic ,Humans ,National Institute of Neurological Disorders and Stroke (U.S.) ,Nervous System Diseases ,Neurology ,Neurosciences ,United States - Abstract
IMPORTANCE: One major advantage of developing large, federally funded networks for clinical research in neurology is the ability to have a trial-ready network that can efficiently conduct scientifically rigorous projects to improve the health of people with neurologic disorders. OBSERVATIONS: National Institute of Neurological Disorders and Stroke Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT) was established in 2011 and renewed in 2018 with the goal of being an efficient network to test between 5 and 7 promising new agents in phase II clinical trials. A clinical coordinating center, data coordinating center, and 25 sites were competitively chosen. Common infrastructure was developed to accelerate timelines for clinical trials, including central institutional review board (a first for the National Institute of Neurological Disorders and Stroke), master clinical trial agreements, the use of common data elements, and experienced research sites and coordination centers. During the first 7 years, the network exceeded the goal of conducting 5 to 7 studies, with 9 funded. High interest was evident by receipt of 148 initial applications for potential studies in various neurologic disorders. Across the first 8 studies (the ninth study was funded at end of initial funding period), the central institutional review board approved the initial protocol in a mean (SD) of 59 (21) days, and additional sites were added a mean (SD) of 22 (18) days after submission. The median time from central institutional review board approval to first site activation was 47.5 days (mean, 102.1; range, 1-282) and from first site activation to first participant consent was 27 days (mean, 37.5; range, 0-96). The median time for database readiness was 3.5 months (mean, 4.0; range, 0-8) from funding receipt. In the 4 completed studies, enrollment met or exceeded expectations with 96% overall data accuracy across all sites. Nine peer-reviewed manuscripts were published, and 22 oral presentations or posters and 9 invited presentations were given at regional, national, and international meetings. CONCLUSIONS AND RELEVANCE: NeuroNEXT initiated 8 studies, successfully enrolled participants at or ahead of schedule, collected high-quality data, published primary results in high-impact journals, and provided mentorship, expert statistical, and trial management support to several new investigators. Partnerships were successfully created between government, academia, industry, foundations, and patient advocacy groups. Clinical trial consortia can efficiently and successfully address a range of important neurologic research and therapeutic questions.
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- 2020
20. Use of Neuroimaging to Inform Optimal Neurocognitive Criteria for Detecting HIV-Associated Brain Abnormalities
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Campbell, Laura M, Fennema-Notestine, Christine, Saloner, Rowan, Hussain, Mariam, Chen, Anna, Franklin, Donald, Umlauf, Anya, Ellis, Ronald J, Collier, Ann C, Marra, Christina M, Clifford, David B, Gelman, Benjamin B, Sacktor, Ned, Morgello, Susan, McCutchan, J Allen, Letendre, Scott, Grant, Igor, and Heaton, Robert K
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Biomedical and Clinical Sciences ,Clinical Sciences ,Psychology ,Basic Behavioral and Social Science ,Infectious Diseases ,Behavioral and Social Science ,Brain Disorders ,Acquired Cognitive Impairment ,HIV/AIDS ,Biomedical Imaging ,Sexually Transmitted Infections ,Mental Health ,Substance Misuse ,Neurosciences ,Neurodegenerative ,Mental health ,Good Health and Well Being ,Activities of Daily Living ,Adult ,Cerebral Cortex ,Cross-Sectional Studies ,Female ,HIV Infections ,Humans ,Inflammation ,Magnetic Resonance Imaging ,Magnetic Resonance Spectroscopy ,Male ,Middle Aged ,Neurocognitive Disorders ,Neuroimaging ,Practice Guidelines as Topic ,Magnetic resonance imaging ,Magnetic resonance spectroscopy ,Cognition ,Infectious disease ,HIV-associated neurocognitive disorders ,Frascati criteria ,CHARTER Group ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Experimental Psychology ,Biomedical and clinical sciences ,Health sciences - Abstract
ObjectiveFrascati international research criteria for HIV-associated neurocognitive disorders (HAND) are controversial; some investigators have argued that Frascati criteria are too liberal, resulting in a high false positive rate. Meyer et al. recommended more conservative revisions to HAND criteria, including exploring other commonly used methodologies for neurocognitive impairment (NCI) in HIV including the global deficit score (GDS). This study compares NCI classifications by Frascati, Meyer, and GDS methods, in relation to neuroimaging markers of brain integrity in HIV.MethodTwo hundred forty-one people living with HIV (PLWH) without current substance use disorder or severe (confounding) comorbid conditions underwent comprehensive neurocognitive testing and brain structural magnetic resonance imaging and magnetic resonance spectroscopy. Participants were classified using Frascati criteria versus Meyer criteria: concordant unimpaired [Frascati(Un)/Meyer(Un)], concordant impaired [Frascati(Imp)/Meyer(Imp)], or discordant [Frascati(Imp)/Meyer(Un)] which were impaired via Frascati criteria but unimpaired via Meyer criteria. To investigate the GDS versus Meyer criteria, the same groupings were utilized using GDS criteria instead of Frascati criteria.ResultsWhen examining Frascati versus Meyer criteria, discordant Frascati(Imp)/Meyer(Un) individuals had less cortical gray matter, greater sulcal cerebrospinal fluid volume, and greater evidence of neuroinflammation (i.e., choline) than concordant Frascati(Un)/Meyer(Un) individuals. GDS versus Meyer comparisons indicated that discordant GDS(Imp)/Meyer(Un) individuals had less cortical gray matter and lower levels of energy metabolism (i.e., creatine) than concordant GDS(Un)/Meyer(Un) individuals. In both sets of analyses, the discordant group did not differ from the concordant impaired group on any neuroimaging measure.ConclusionsThe Meyer criteria failed to capture a substantial portion of PLWH with brain abnormalities. These findings support continued use of Frascati or GDS criteria to detect HIV-associated CNS dysfunction.
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- 2020
21. Correlates of HIV RNA concentrations in cerebrospinal fluid during antiretroviral therapy: a longitudinal cohort study.
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Livelli, Alessandro, Vaida, Florin, Ellis, Ronald J, Ma, Qing, Ferrara, Micol, Clifford, David B, Collier, Ann C, Gelman, Benjamin B, Marra, Christina M, McArthur, Justin C, McCutchan, J Allen, Morgello, Susan, Sacktor, Ned, Simpson, David M, Grant, Igor, Letendre, Scott L, and CHARTER Group
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CHARTER Group ,Cerebrospinal Fluid ,Humans ,HIV-1 ,HIV Infections ,RNA ,Viral ,Anti-Retroviral Agents ,CD4 Lymphocyte Count ,Treatment Outcome ,Antiretroviral Therapy ,Highly Active ,Viral Load ,Odds Ratio ,Longitudinal Studies ,Adult ,Middle Aged ,Female ,Male ,Mental Health ,Pediatric ,Brain Disorders ,HIV/AIDS ,Infectious Diseases ,Pediatric AIDS ,Infection ,Good Health and Well Being ,Medical and Health Sciences - Abstract
BackgroundFew large projects have evaluated the factors that influence the HIV RNA concentrations (viral load) in cerebrospinal fluid (CSF) during antiretroviral therapy (ART) over time. We aimed to determine the correlates of HIV RNA in CSF in a large cohort.MethodsWe analysed longitudinal data from adults living with HIV in the US CHARTER cohort. Participants in the CHARTER study were recruited from six US academic medical centres-in Baltimore (MD), Galveston (TX), New York (NY), St Louis (MO), San Diego (C92A), and Seattle (WA). Participants in this study had been assessed at least three times between Sept 4, 2003, and Sept 14, 2010, and were taking ART and underwent venous and lumbar puncture with measurement of HIV RNA concentration at all assessments. The lower limit of quantification of the HIV RNA assays was 50 copies per mL. Data were analysed with longitudinal mixed effects logistic regression to identify correlates of HIV RNA concentration (as a binary [detectable or not] and as a continuous variable) in CSF over time. We tested demographic characteristics, plasma HIV RNA, nadir and current CD4 cell count in blood, current CD8 cell count in blood, estimated duration of HIV infection, AIDS diagnosis, duration of ART, adherence to ART, ART characteristics, and CSF characteristics as potential correlates.FindingsAt the time of analysis, 2207 assessments from 401 participants met the criteria for inclusion in this study. Mean duration of observation was 33·7 months (range 12-84). HIV RNA concentrations in 710 (32·2%) plasma specimens and in 255 (11·6%) CSF specimens were greater than the lower limit of quantification. The best multivariate model of HIV RNA concentration in CSF greater than the lower limit of quantification over time included increased plasma HIV RNA concentration (odds ratio 18·0 per 1 log10 copy per mL, 95% CI 11·3 to 28·8; p
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- 2019
22. Effects of comorbidity burden and Age on brain integrity in HIV
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Saloner, Rowan, Heaton, Robert K, Campbell, Laura M, Chen, Anna, Franklin, Donald, Ellis, Ronald J, Collier, Ann C, Marra, Christina, Clifford, David B, Gelman, Benjamin, Sacktor, Ned, Morgello, Susan, McCutchan, J Allen, Letendre, Scott, Grant, Igor, and Fennema-Notestine, Christine
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Biomedical and Clinical Sciences ,Clinical Sciences ,Aging ,Brain Disorders ,Acquired Cognitive Impairment ,Infectious Diseases ,Behavioral and Social Science ,Neurosciences ,Clinical Research ,Mental Health ,HIV/AIDS ,Adult ,Anti-Retroviral Agents ,Brain ,Cohort Studies ,Comorbidity ,Cross-Sectional Studies ,Female ,Gray Matter ,HIV ,HIV Infections ,Humans ,Linear Models ,Magnetic Resonance Imaging ,Magnetic Resonance Spectroscopy ,Male ,Middle Aged ,Multivariate Analysis ,Neuroimaging ,Neuropsychological Tests ,Sustained Virologic Response ,White Matter ,aging ,brain ,comorbidity ,MRI ,magnetic resonance spectroscopy ,neurocognitive disorders ,CHARTER Study Group ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Virology ,Biomedical and clinical sciences ,Health sciences - Abstract
ObjectiveThe influence of confounding neurocognitive comorbidities in people living with HIV (PLWH) on neuroimaging has not been systematically evaluated. We determined associations between comorbidity burden and brain integrity and examined the moderating effect of age on these relationships.DesignObservational, cross-sectional substudy of the CNS HIV Antiretroviral Therapy Effects Research cohort.MethodsA total of 288 PLWH (mean age = 44.2) underwent structural MRI and magnetic resonance spectroscopy as well as neurocognitive and neuromedical assessments. Consistent with Frascati criteria for HIV-associated neurocognitive disorders (HAND), neuromedical and neuropsychiatric comorbidity burden was classified as incidental (mild), contributing (moderate), or confounding (severe-exclusionary) to a diagnosis of HAND. Multiple regression modeling predicted neuroimaging outcomes as a function of comorbidity classification, age, and their interaction.ResultsComorbidity classifications were 176 incidental, 77 contributing, and 35 confounded; groups did not differ in HIV disease characteristics. Relative to incidental and contributing participants, confounded participants had less cortical gray matter and more abnormal white matter and ventricular cerebrospinal fluid, alongside more neuroinflammation (choline, myo-inositol) and less neuronal integrity (N-acetylaspartate). Older age exacerbated the impact of comorbidity burden: to a greater extent in the confounded group, older age was associated with more abnormal white matter (P = 0.017), less total white matter (P = 0.015), and less subcortical gray matter (P = 0.014).ConclusionNeuroimaging in PLWH reveals signatures associated with confounding neurocognitive conditions, emphasizing the importance of evaluating these among individuals with suspected HAND. Older age amplifies subcortical and white matter tissue injury, especially in PLWH with severe comorbidity burden, warranting increased attention to this population as it ages.
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- 2019
23. Neurocognitive SuperAging in Older Adults Living With HIV: Demographic, Neuromedical and Everyday Functioning Correlates
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Saloner, Rowan, Campbell, Laura M, Serrano, Vanessa, Montoya, Jessica L, Pasipanodya, Elizabeth, Paolillo, Emily W, Franklin, Donald, Ellis, Ronald J, Letendre, Scott L, Collier, Ann C, Clifford, David B, Gelman, Benjamin B, Marra, Christina M, McCutchan, J Allen, Morgello, Susan, Sacktor, Ned, Jeste, Dilip V, Grant, Igor, Heaton, Robert K, and Moore, David J
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Psychology ,Biomedical and Clinical Sciences ,Applied and Developmental Psychology ,Prevention ,Infectious Diseases ,HIV/AIDS ,Clinical Research ,Mental Health ,Behavioral and Social Science ,Neurosciences ,Aging ,Good Health and Well Being ,Activities of Daily Living ,Cognition ,Cognitive Aging ,Cognitive Reserve ,Employment ,Female ,HIV Infections ,Healthy Lifestyle ,Humans ,Male ,Marijuana Use ,Middle Aged ,Quality of Life ,Neuropsychology ,Cognitive reserve ,Cognitive decline ,Diabetes ,Cannabis ,Acquired Immunodeficiency Syndrome ,CHARTER and HNRP Groups ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Experimental Psychology ,Biomedical and clinical sciences ,Health sciences - Abstract
ObjectivesStudies of neurocognitively elite older adults, termed SuperAgers, have identified clinical predictors and neurobiological indicators of resilience against age-related neurocognitive decline. Despite rising rates of older persons living with HIV (PLWH), SuperAging (SA) in PLWH remains undefined. We aimed to establish neuropsychological criteria for SA in PLWH and examined clinically relevant correlates of SA.Methods734 PLWH and 123 HIV-uninfected participants between 50 and 64 years of age underwent neuropsychological and neuromedical evaluations. SA was defined as demographically corrected (i.e., sex, race/ethnicity, education) global neurocognitive performance within normal range for 25-year-olds. Remaining participants were labeled cognitively normal (CN) or impaired (CI) based on actual age. Chi-square and analysis of variance tests examined HIV group differences on neurocognitive status and demographics. Within PLWH, neurocognitive status differences were tested on HIV disease characteristics, medical comorbidities, and everyday functioning. Multinomial logistic regression explored independent predictors of neurocognitive status.ResultsNeurocognitive status rates and demographic characteristics differed between PLWH (SA=17%; CN=38%; CI=45%) and HIV-uninfected participants (SA=35%; CN=55%; CI=11%). In PLWH, neurocognitive groups were comparable on demographic and HIV disease characteristics. Younger age, higher verbal IQ, absence of diabetes, fewer depressive symptoms, and lifetime cannabis use disorder increased likelihood of SA. SA reported increased independence in everyday functioning, employment, and health-related quality of life than non-SA.ConclusionsDespite combined neurological risk of aging and HIV, youthful neurocognitive performance is possible for older PLWH. SA relates to improved real-world functioning and may be better explained by cognitive reserve and maintenance of cardiometabolic and mental health than HIV disease severity. Future research investigating biomarker and lifestyle (e.g., physical activity) correlates of SA may help identify modifiable neuroprotective factors against HIV-related neurobiological aging. (JINS, 2019, 25, 507-519).
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- 2019
24. Cerebrospinal fluid viral escape in aviremic HIV-infected patients receiving antiretroviral therapy
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Pérez-Valero, Ignacio, Ellis, Ronald, Heaton, Robert, Deutsch, Reena, Franklin, Donald, Clifford, David B, Collier, Ann, Gelman, Benjamin, Marra, Christina, McCutchan, John Allen, Navis, Allison, Sacktor, Ned, Simpson, David, Grant, Igor, and Letendre, Scott
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Brain Disorders ,Genetics ,Neurosciences ,Clinical Research ,Infectious Diseases ,HIV/AIDS ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Infection ,Good Health and Well Being ,Anti-Retroviral Agents ,Antiretroviral Therapy ,Highly Active ,Cerebrospinal Fluid ,Cross-Sectional Studies ,Female ,HIV Infections ,Humans ,Male ,Middle Aged ,Neuropsychological Tests ,Plasma ,Prevalence ,RNA ,Viral ,Risk Factors ,Sustained Virologic Response ,Treatment Outcome ,United States ,antiretroviral therapy ,cerebrospinal fluid viral escape ,HIV neurocognitive disorder ,HIV-1 ,neurocognitive impairment ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Virology ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundDuring antiretroviral therapy, HIV RNA can be detected in cerebrospinal fluid (CSF) when it is undetectable in plasma, a condition termed 'CSF viral escape'. The aim of the current study was to determine the prevalence and risk factors for CSF viral escape in two large cohorts in the USA.MethodsA total of 1264 HIV-infected volunteers enrolled in two US cohorts at their most recent visit between 2003 and 2011 were included in this cross-sectional analysis if their HIV RNA level in plasma was less than 50 copies/ml while receiving stable antiretroviral therapy (ART) (>6 months) and if they had HIV RNA measured in CSF at their most recent visit between 2003 and 2011. Potential risk factors were identified using univariable and multivariable regression.ResultsCSF viral escape was detected in 55 adults (4.4%; 95% CI: 3.4-5.6), who had a median CSF HIV RNA of 155 copies/ml [interquartile range (IQR: 80-283)]. Patients with or without CSF viral escape had similar rates of neurocognitive impairment (38.2 vs. 37.7%; P = 0.91). CSF viral escape was independently associated with the use of ritonavir-boosted protease inhibitors [odds ratio (OR): 2.0; 95% CI: 1.1-3.8] or unboosted atazanavir (OR: 5.1; 95% CI: 1.3-16.1), CSF pleocytosis (OR: 7.6; 95% CI: 4.2-13.7) and abnormal CSF total protein (OR: 2.1; 95% CI: 1.1-3.7).ConclusionsIn this large study of aviremic patients receiving ART, CSF viral escape was uncommon and was linked to evidence of central nervous system inflammation and the use of protease inhibitors, but not with worse neurocognitive performance.
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- 2019
25. White matter damage, neuroinflammation, and neuronal integrity in HAND
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Alakkas, Aljoharah, Ellis, Ronald J, Watson, Caitlin Wei-Ming, Umlauf, Anya, Heaton, Robert K, Letendre, Scott, Collier, Ann, Marra, Christina, Clifford, David B, Gelman, Benjamin, Sacktor, Ned, Morgello, Susan, Simpson, David, McCutchan, J Allen, Kallianpur, Asha, Gianella, Sara, Marcotte, Thomas, Grant, Igor, and Fennema-Notestine, Christine
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Biomedical and Clinical Sciences ,Clinical Sciences ,Mental Health ,HIV/AIDS ,Neurosciences ,Acquired Cognitive Impairment ,Clinical Research ,Infectious Diseases ,Biomedical Imaging ,Brain Disorders ,Aetiology ,2.1 Biological and endogenous factors ,Neurological ,AIDS Dementia Complex ,Adult ,Anti-HIV Agents ,Antiretroviral Therapy ,Highly Active ,Aspartic Acid ,Basal Ganglia ,CD4 Lymphocyte Count ,CD4-Positive T-Lymphocytes ,Choline ,Cognitive Dysfunction ,Creatine ,Female ,Gray Matter ,Humans ,Longitudinal Studies ,Magnetic Resonance Imaging ,Male ,Memory ,Short-Term ,Middle Aged ,Neuroimaging ,Neuropsychological Tests ,Organ Size ,Severity of Illness Index ,White Matter ,HAND ,MRI ,CHARTER Group ,Hand Mri ,Medical Microbiology ,Virology ,Clinical sciences ,Medical microbiology - Abstract
HIV-associated neurocognitive disorders (HANDs) persist even with virologic suppression on combination antiretroviral therapy (cART), and the underlying pathophysiological mechanisms are not well understood. We performed structural magnetic resonance imaging and MR spectroscopy (MRS) in HIV+ individuals without major neurocognitive comorbidities. Study participants were classified as neurocognitively unimpaired (NU), asymptomatic (ANI), mild neurocognitive disorder (MND), or HIV-associated dementia (HAD). Using structural MRI, we measured volumes of cortical and subcortical gray matter and total and abnormal white matter (aWM). Using single-voxel MRS, we estimated metabolites in frontal gray matter (FGM) and frontal white matter (FWM) and basal ganglia (BG) regions. Adjusted odds ratios were used to compare HAND to NU. Among 253 participants, 40% met HAND criteria (21% ANI, 15% MND, and 4% HAD). Higher risk of HAND was associated with more aWM. Both HAD and MND also had smaller gray and white matter volumes than NU. Among individuals with undetectable plasma HIV RNA, structural volumetric findings were similar to the overall sample. MND had lower FWM creatine and higher FGM choline relative to NU, whereas HAD and ANI had lower BG N-acetyl aspartate relative to NU. In the virologically suppressed subgroup, however, ANI and MND had higher FGM choline compared to NU. Overall, HAND showed specific alterations (more aWM and inflammation; less gray matter volume and lower NAA). Some MR measures differentiated less severe subtypes of HAND from HAD. These MR alterations may represent legacy effects or accumulating changes, possibly related to medical comorbidities, antiretroviral therapy, or chronic effects of HIV brain infection.
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- 2019
26. Spatial inequalities in charitable fundraising and income generation for NHS acute trusts in England.
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Mohan, John and Clifford, David
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FUNDRAISING ,INCOME ,INCOME inequality ,SPATIAL variation ,NATIONAL income - Abstract
IMPACT: This article presents novel analyses of the income sources of National Health Service (NHS) acute trusts in England. The results suggest that there are variations according to deprivation in the extent of private financial resources available to NHS institutions. They suggest a need to open up discussions about how best to mitigate spatial differences in the charitable and private patient income of NHS trusts, particularly if these sources of income grow in importance going forward. The article provides—for the first time—an analysis of spatial variation in the income sources of National Health Service (NHS) acute trusts in England. It shows that, compared to trusts serving less deprived communities, trusts serving more deprived communities receive a lower proportion of income from charitable sources; and that trusts serving deprived communities also receive a lower proportion of income from private patients. The study serves to provide evidence of spatial inequality in the private resources that support local public institutions. [ABSTRACT FROM AUTHOR]
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- 2024
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27. Passing or Dropping the Baton? Local Area Deprivation, Volunteer Leadership Succession and the Survival of Charitable Organisations.
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Clifford, David
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CHARITIES , *URBAN sociology , *VOLUNTEER service , *ORGANIZATION management , *HYPOTHESIS - Abstract
Institutional theories of 'local area effects' hypothesise that local area differences in organisational resources are an important feature of inequality in individuals' residential environments. However, while the organisational dimension of local areas has been identified as an important research priority within urban sociology, empirical work remains limited, with charitable organisations particularly under-researched. Therefore, a key question remains unanswered: why do charities in more deprived local areas have higher dissolution rates, reinforcing a lower prevalence of charities compared with less deprived areas? This article focuses on this research problem. It shows that volunteer leadership succession is less prominent in more deprived local areas, and that this more limited leadership succession helps explain why charities in more deprived areas experience higher dissolution rates. The results promote understanding of a mechanism underlying local area differences in organisational dynamics that lead to persistent differences in institutional resources between more and less deprived local areas. [ABSTRACT FROM AUTHOR]
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- 2024
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28. Differences in Neurocognitive Impairment Among HIV-Infected Latinos in the United States
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Marquine, María J, Heaton, Anne, Johnson, Neco, Rivera-Mindt, Monica, Cherner, Mariana, Bloss, Cinnamon, Hulgan, Todd, Umlauf, Anya, Moore, David J, Fazeli, Pariya, Morgello, Susan, Franklin, Donald, Letendre, Scott, Ellis, Ron, Collier, Ann C, Marra, Christina M, Clifford, David B, Gelman, Benjamin B, Sacktor, Ned, Simpson, David, McCutchan, J Allen, Grant, Igor, and Heaton, Robert K
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Medical Microbiology ,Biomedical and Clinical Sciences ,HIV/AIDS ,Clinical Research ,Infection ,Good Health and Well Being ,Adult ,Cognitive Dysfunction ,Executive Function ,Female ,HIV Infections ,Hispanic or Latino ,Humans ,Learning ,Male ,Mexico ,Psychomotor Performance ,Puerto Rico ,United States ,White People ,Young Adult ,Hispanics ,Human immunodeficiency virus ,Culture ,Cognitive function ,Minority health ,Health status disparities ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Experimental Psychology ,Biomedical and clinical sciences ,Health sciences ,Psychology - Abstract
ObjectivesHuman immunodeficiency virus (HIV) disproportionately affects Hispanics/Latinos in the United States, yet little is known about neurocognitive impairment (NCI) in this group. We compared the rates of NCI in large well-characterized samples of HIV-infected (HIV+) Latinos and (non-Latino) Whites, and examined HIV-associated NCI among subgroups of Latinos.MethodsParticipants included English-speaking HIV+ adults assessed at six U.S. medical centers (194 Latinos, 600 Whites). For overall group, age: M=42.65 years, SD=8.93; 86% male; education: M=13.17, SD=2.73; 54% had acquired immunodeficiency syndrome. NCI was assessed with a comprehensive test battery with normative corrections for age, education and gender. Covariates examined included HIV-disease characteristics, comorbidities, and genetic ancestry.ResultsCompared with Whites, Latinos had higher rates of global NCI (42% vs. 54%), and domain NCI in executive function, learning, recall, working memory, and processing speed. Latinos also fared worse than Whites on current and historical HIV-disease characteristics, and nadir CD4 partially mediated ethnic differences in NCI. Yet, Latinos continued to have more global NCI [odds ratio (OR)=1.59; 95% confidence interval (CI)=1.13-2.23; p
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- 2018
29. Cerebrospinal fluid cell-free mitochondrial DNA is associated with HIV replication, iron transport, and mild HIV-associated neurocognitive impairment
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Mehta, Sanjay R, Pérez-Santiago, Josué, Hulgan, Todd, Day, Tyler RC, Barnholtz-Sloan, Jill, Gittleman, Haley, Letendre, Scott, Ellis, Ronald, Heaton, Robert, Patton, Stephanie, Suben, Jesse D, Franklin, Donald, Rosario, Debralee, Clifford, David B, Collier, Ann C, Marra, Christina M, Gelman, Benjamin B, McArthur, Justin, McCutchan, Allen, Morgello, Susan, Simpson, David, Connor, James, Grant, Igor, and Kallianpur, Asha
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Neurosciences ,Infectious Diseases ,HIV/AIDS ,Clinical Research ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Infection ,Good Health and Well Being ,AIDS Dementia Complex ,Adult ,Biomarkers ,Cell-Free Nucleic Acids ,Cohort Studies ,Cross-Sectional Studies ,DNA ,Mitochondrial ,Female ,HIV ,Humans ,Iron ,Male ,Middle Aged ,Viral Load ,Virus Replication ,Mitochondrial DNA ,Cerebrospinal fluid ,Neurocognitive impairment ,Inflammation ,Clinical Sciences ,Neurology & Neurosurgery - Abstract
BackgroundMitochondria are abundant organelles critical for energy metabolism and brain function. Mitochondrial DNA (mtDNA), released during cellular injury and as part of the innate immune response to viral pathogens, contains CpG motifs that act as TLR-9 ligands. We investigated relationships between cerebrospinal fluid (CSF) cell-free mtDNA levels and HIV viral load (VL), biomarkers of inflammation and iron transport, and neurocognitive (NC) function in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) cohort.MethodsWe quantified cell-free mtDNA in CSF by droplet digital PCR in 332 CHARTER participants who underwent comprehensive neuropsychiatric evaluation. NC performance was assessed using the global deficit score (GDS) as either a continuous or a binary measure (GDS ≥ 0.5, impaired vs. GDS
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- 2017
30. Infliximab for the treatment of CNS sarcoidosis
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Gelfand, Jeffrey M, Bradshaw, Michael J, Stern, Barney J, Clifford, David B, Wang, Yunxia, Cho, Tracey A, Koth, Laura L, Hauser, Stephen L, Dierkhising, Jason, Vu, NgocHanh, Sriram, Subramaniam, Moses, Harold, Bagnato, Francesca, Kaufmann, Jeffrey A, Ammah, Deidre J, Yohannes, Tsion H, Hamblin, Mark J, Venna, Nagagopal, Green, Ari J, and Pawate, Siddharama
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Neurosciences ,Clinical Research ,Biomedical Imaging ,Brain Disorders ,Autoimmune Disease ,Adult ,Aged ,Central Nervous System Diseases ,Female ,Humans ,Immunosuppressive Agents ,Infliximab ,Male ,Middle Aged ,Outcome Assessment ,Health Care ,Sarcoidosis ,Tumor Necrosis Factor-alpha ,Young Adult ,Clinical Sciences ,Cognitive Sciences ,Neurology & Neurosurgery - Abstract
ObjectiveTo describe clinical and imaging responses in neurosarcoidosis to infliximab, a monoclonal antibody against tumor necrosis factor-α.MethodsInvestigators at 6 US centers retrospectively identified patients with CNS sarcoidosis treated with infliximab, including only patients with definite or probable neurosarcoidosis following rigorous exclusion of other causes.ResultsOf 66 patients with CNS sarcoidosis (27 definite, 39 probable) treated with infliximab for a median of 1.5 years, the mean age was 47.5 years at infliximab initiation (SD 11.7, range 24-71 years); 56.1% were female; 62.1% were white, 37.0% African American, and 3% Hispanic. Sarcoidosis was isolated to the CNS in 19.7%. Using infliximab doses ranging from 3 to 7 mg/kg every 4-8 weeks, MRI evidence of a favorable treatment response was observed in 82.1% of patients with imaging follow-up (n = 56), with complete remission of active disease in 51.8% and partial MRI improvement in 30.1%; MRI worsened in 1 patient (1.8%). There was clinical improvement in 77.3% of patients, with complete neurologic recovery in 28.8%, partial improvement in 48.5%, clinical stability in 18.2%, worsening in 3%, and 1 lost to follow-up. In 16 patients in remission when infliximab was discontinued, the disease recurred in 9 (56%), typically in the same neuroanatomic location.ConclusionsMost patients with CNS sarcoidosis treated with infliximab exhibit favorable imaging and clinical treatment responses, including some previously refractory to other immunosuppressive treatments.Classification of evidenceThis study provides Class IV evidence that for patients with CNS sarcoidosis infliximab is associated with favorable imaging and clinical responses.
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- 2017
31. A trial of gantenerumab or solanezumab in dominantly inherited Alzheimer's disease
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Salloway, Stephen, Farlow, Martin, McDade, Eric, Clifford, David B., Wang, Guoqiao, Llibre-Guerra, Jorge J., and Hitchcock, Janice M.
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Alzheimer's disease -- Drug therapy -- Care and treatment ,Biological sciences ,Health - Abstract
Dominantly inherited Alzheimer's disease (DIAD) causes predictable biological changes decades before the onset of clinical symptoms, enabling testing of interventions in the asymptomatic and symptomatic stages to delay or slow disease progression. We conducted a randomized, placebo-controlled, multi-arm trial of gantenerumab or solanezumab in participants with DIAD across asymptomatic and symptomatic disease stages. Mutation carriers were assigned 3:1 to either drug or placebo and received treatment for 4-7 years. The primary outcome was a cognitive end point; secondary outcomes included clinical, cognitive, imaging and fluid biomarker measures. Fifty-two participants carrying a mutation were assigned to receive gantenerumab, 52 solanezumab and 40 placebo. Both drugs engaged their A[beta] targets but neither demonstrated a beneficial effect on cognitive measures compared to controls. The solanezumab-treated group showed a greater cognitive decline on some measures and did not show benefits on downstream biomarkers. Gantenerumab significantly reduced amyloid plaques, cerebrospinal fluid total tau, and phospho-tau181 and attenuated increases of neurofilament light chain. Amyloid-related imaging abnormalities edema was observed in 19.2% (3 out of 11 were mildly symptomatic) of the gantenerumab group, 2.5% of the placebo group and 0% of the solanezumab group. Gantenerumab and solanezumab did not slow cognitive decline in symptomatic DIAD. The asymptomatic groups showed no cognitive decline; symptomatic participants had declined before reaching the target doses. Results from the phase 2/3 clinical trial of gantenerumab or solanezumab in dominantly inherited Alzheimer's disease reveal no beneficial effects on cognitive measures despite a significant reduction in amyloid plaques and other key biomarkers in those treated with gantenerumab., Author(s): Stephen Salloway [sup.1] , Martin Farlow [sup.2] , Eric McDade [sup.3] , David B. Clifford [sup.3] , Guoqiao Wang [sup.3] , Jorge J. Llibre-Guerra [sup.3] , Janice M. Hitchcock [...]
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- 2021
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32. Correlates of HIV RNA concentrations in cerebrospinal fluid during antiretroviral therapy: a longitudinal cohort study
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Abramson, Ian, Al-Lozi, Muhammad T., Archibald, Sarah L., Atkinson, J. Hampton, Best, Brookie M., Clifford, David B., Collier, Ann C., Cushman, Clint, Dawson, Matthew S., Ellis, Ronald J., Fennema-Notestine, Christine, Franklin, Donald R., Gelman, Benjamin B., Grant, Igor, Head, Eleanor, Heaton, Robert K., Jones, Trudy, Letendre, Scott, Maravilla, Kenneth R., Marcotte, Thomas D., Marra, Christina M., McArthur, Justin C., McCutchan, J. Allen, Mintz, Letty, Morgello, Susan, Naidich, Thomas P., Sacktor, Ned, Simpson, David M., Smith, David M., Stegbauer, Keith C., Tang, Cheuk Y., Teshome, Mengesha, Livelli, Alessandro, Vaida, Florin, Ellis, Ronald J, Ma, Qing, Ferrara, Micol, Clifford, David B, Collier, Ann C, Gelman, Benjamin B, Marra, Christina M, McArthur, Justin C, McCutchan, J Allen, Simpson, David M, and Letendre, Scott L
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- 2019
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33. IgG4-Related Disease of the Skull and Skull Base–A Systematic Review and Report of Two Cases
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Cler, Samuel J., Sharifai, Nima, Baker, Brandi, Dowling, Joshua L., Pipkorn, Patrik, Yaeger, Lauren, Clifford, David B., Dahiya, Sonika, and Chicoine, Michael R.
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- 2021
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34. Genome‐wide association study of HIV‐associated neurocognitive disorder (HAND): A CHARTER group study
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Jia, Peilin, Zhao, Zhongming, Hulgan, Todd, Bush, William S, Samuels, David C, Bloss, Cinnamon S, Heaton, Robert K, Ellis, Ronald J, Schork, Nicholas, Marra, Christina M, Collier, Ann C, Clifford, David B, Gelman, Benjamin B, Sacktor, Ned, Morgello, Susan, Simpson, David M, McCutchan, J Allen, Barnholtz‐Sloan, Jill S, Franklin, Donald R, Rosario, Debralee, Letendre, Scott L, Grant, Igor, Kallianpur, Asha R, and Group, for the CHARTER Study
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Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Mental Health ,HIV/AIDS ,Human Genome ,Infectious Diseases ,Neurosciences ,Prevention ,Brain Disorders ,2.1 Biological and endogenous factors ,Aetiology ,Good Health and Well Being ,AIDS Dementia Complex ,Adult ,Biomarkers ,Female ,Follow-Up Studies ,Genome-Wide Association Study ,Genotype ,Humans ,Male ,Middle Aged ,Neurocognitive Disorders ,Neuropsychological Tests ,Polymorphism ,Single Nucleotide ,Prognosis ,Prospective Studies ,HIV-associated neurocognitive disorder ,neuro-cognitive impairment ,GWAS ,genotype ,CHARTER study ,global deficit score ,CHARTER Study Group ,neurocognitive impairment ,Clinical Sciences ,Clinical sciences - Abstract
HIV-associated neurocognitive disorder (HAND) often complicates HIV infection despite combination antiretroviral therapy (ART) and may be influenced by host genomics. We performed a genome-wide association study (GWAS) of HAND in 1,050 CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) Study participants. All participants underwent standardized, comprehensive neurocognitive, and neuromedical assessments to determine if they had cognitive impairment as assessed by the Global Deficit Score (GDS), and individuals with comorbidities that could confound diagnosis of HAND were excluded. Neurocognitive outcomes included GDS-defined neurocognitive impairment (NCI; binary GDS, 366 cases with GDS ≥ 0.5 and 684 controls with GDS
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- 2017
35. JC virus granule cell neuronopathy in the setting of chronic lymphopenia treated with recombinant interleukin-7
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Soleimani-Meigooni, David N, Schwetye, Katherine E, Angeles, Maria Reyes, Ryschkewitsch, Caroline F, Major, Eugene O, Dang, Xin, Koralnik, Igor J, Schmidt, Robert E, Clifford, David B, Kuhlmann, F Matthew, and Bucelli, Robert C
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Biomedical and Clinical Sciences ,Immunology ,Brain Disorders ,Neurosciences ,Infectious Diseases ,Rare Diseases ,Biotechnology ,Aged ,Ataxia ,Chronic Disease ,Hamartoma Syndrome ,Multiple ,Humans ,Immunocompromised Host ,Immunoglobulins ,Intravenous ,Interleukin-7 ,JC Virus ,Leukoencephalopathy ,Progressive Multifocal ,Lymphopenia ,Male ,Malformations of Cortical Development ,Group I ,Mefloquine ,Methylprednisolone ,Mianserin ,Mirtazapine ,Recombinant Proteins ,Cerebellar ataxia ,Granule cell neuronopathy ,Il-7 ,JC virus ,Clinical Sciences ,Medical Microbiology ,Virology ,Clinical sciences ,Medical microbiology - Abstract
JC virus (JCV) is a human polyomavirus that infects the central nervous system (CNS) of immunocompromised patients. JCV granule cell neuronopathy (JCV-GCN) is caused by infection of cerebellar granule cells, causing ataxia. A 77-year-old man with iatrogenic lymphopenia presented with severe ataxia and was diagnosed with JCV-GCN. His ataxia and cerebrospinal fluid (CSF) improved with intravenous immunoglobulin, high-dose intravenous methylprednisolone, mirtazapine, and mefloquine. Interleukin-7 (IL-7) therapy reconstituted his lymphocytes and reduced his CSF JCV load. One month after IL-7 therapy, he developed worsening ataxia and CSF inflammation, which raised suspicion for immune reconstitution inflammatory syndrome. Steroids were restarted and his ataxia stabilized.
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- 2017
36. Evaluating the accuracy of self-report for the diagnosis of HIV-associated neurocognitive disorder (HAND): defining “symptomatic” versus “asymptomatic” HAND
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Obermeit, Lisa C, Beltran, Jessica, Casaletto, Kaitlin B, Franklin, Donald R, Letendre, Scott, Ellis, Ronald, Fennema-Notestine, Christine, Vaida, Florin, Collier, Ann C, Marra, Christina M, Clifford, David, Gelman, Benjamin, Sacktor, Ned, Morgello, Susan, Simpson, David, McCutchan, J Allen, Grant, Igor, Heaton, Robert K, and The CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) Group
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Medical Microbiology ,Biomedical and Clinical Sciences ,Neurosciences ,Clinical Sciences ,Rehabilitation ,Mental Health ,HIV/AIDS ,Infectious Diseases ,Behavioral and Social Science ,Clinical Research ,Sexually Transmitted Infections ,Neurodegenerative ,Acquired Cognitive Impairment ,Brain Disorders ,Activities of Daily Living ,Adult ,Asymptomatic Diseases ,Cognition ,Cognitive Dysfunction ,Disabled Persons ,Female ,HIV Infections ,Humans ,Male ,Middle Aged ,Psychiatric Status Rating Scales ,Self Report ,Severity of Illness Index ,AIDS ,Activities of daily living ,Self-assessment ,Cognitive disorders ,Etiology ,CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) Group ,Virology ,Clinical sciences ,Medical microbiology - Abstract
The criteria for differentiating symptomatic from asymptomatic HIV-associated neurocognitive disorder require evaluation of (1) cognitive impairment, (2) daily functioning declines, and (3) whether the functional declines are attributable to cognitive versus physical problems. Many providers rely only on self-report to evaluate these latter criteria. However, the accuracy of patient-provided information may be limited. This study evaluated the validity of self-assessment for HIV-associated neurocognitive disorder (HAND) diagnoses by comparing objective findings with self-report of criteria 2 and 3 above. Self-reports were used to stratify 277 cognitively impaired HIV+ individuals into functionally dependent (n = 159) and independent (n = 118) groups, followed by group comparisons of objective functional problems. The dependent group was then divided into those who self-attributed their functional dependence to only cognitive (n = 80) versus only physical (n = 79) causes, for further comparisons on objective findings. The functionally dependent group was significantly worse than the independent group on all objective disability characteristics except severity of cognitive impairment, while those who attributed their dependence to physical (versus cognitive) factors were similar on all objective physical, cognitive, and functioning variables. Of note, 28 % of physical attributors showed no physical abnormalities on neuromedical examinations. Results suggest that patient report is consistently associated with objective measures of functional loss; in contrast, patient identification of physical versus cognitive causes is poorly associated with objective criteria. These findings caution against relying solely on patient self-report to determine whether functional disability in cognitively impaired HIV+ individuals can be attributed to strictly physical causes.
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- 2017
37. Prevalence and Correlates of Persistent HIV-1 RNA in Cerebrospinal Fluid During Antiretroviral Therapy
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Anderson, Albert M, Muñoz-Moreno, Jose A, McClernon, Daniel R, Ellis, Ronald J, Cookson, Debra, Clifford, David B, Collier, Ann C, Gelman, Benjamin B, Marra, Christina M, McArthur, Justin C, McCutchan, J Allen, Morgello, Susan, Sacktor, Ned, Simpson, David M, Franklin, Donald R, Heaton, Robert K, Grant, Igor, and Letendre, Scott L
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Infectious Diseases ,Acquired Cognitive Impairment ,Brain Disorders ,Neurosciences ,Pediatric AIDS ,HIV/AIDS ,Pediatric ,Clinical Research ,Mental Health ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Infection ,Adult ,Anti-HIV Agents ,CD4 Lymphocyte Count ,Female ,HIV Infections ,HIV-1 ,Humans ,Male ,Middle Aged ,Neurocognitive Disorders ,Prevalence ,RNA ,Viral ,Viral Load ,HIV ,cerebrospinal fluid ,cognitive disorders ,antiretroviral therapy ,CHARTER Group ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
Background Neurocognitive disorders remain common among human immunodeficiency virus (HIV)-positive adults, perhaps owing to persistent HIV-1 RNA in cerebrospinal fluid (CSF) during antiretroviral therapy (ART).Methods Using a single-copy assay, we measured HIV-1 RNA levels in CSF and plasma specimens from 220 HIV-positive adults who were taking suppressive ART. Fifty-five participants were tested twice.Results HIV-1 RNA was detected in 42.3% of CSF and 65.2% of plasma samples. Correlates of higher CSF HIV-1 RNA levels included higher nadir and current CD4+ T-cell counts, a plasma HIV-1 RNA level of ≥ 1 copy/mL, and a lower central nervous system penetration-effectiveness score (model P < .001). Worse neurocognitive performance was associated with discordance in HIV-1 RNA detection between plasma and CSF, lower overall CSF HIV-1 RNA level, and longer ART duration, among others (model P < .001). In the longitudinal subgroup, CSF HIV-1 RNA persisted in most participants (69%) over 7 months.Conclusions Low-level HIV-1 RNA in CSF is common during suppressive ART and is associated with low-level HIV-1 RNA in blood, better immune status, and lower ART drug distribution into CSF. The association between HIV-1 RNA discordance and HIV-associated neurocognitive disorder (HAND) may reflect compartmentalization. The relationship between HAND, lower HIV-1 RNA levels in CSF, and lower CD4+ T-cell counts may reflect disturbances in the immune response to HIV-1 in the CNS.
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- 2017
38. Apolipoprotein E ε4 genotype status is not associated with neuroimaging outcomes in a large cohort of HIV+ individuals
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Cooley, Sarah A, Paul, Robert H, Fennema-Notestine, Christine, Morgan, Erin E, Vaida, Florin, Deng, Qianqian, Chen, Jie Ashley, Letendre, Scott, Ellis, Ronald, Clifford, David B, Marra, Christina M, Collier, Ann C, Gelman, Benjamin B, McArthur, Justin C, McCutchan, J Allen, Simpson, David M, Morgello, Susan, Grant, Igor, Ances, Beau M, and for the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) Group
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Medical Microbiology ,Biomedical and Clinical Sciences ,HIV/AIDS ,Brain Disorders ,Clinical Research ,Aging ,Sexually Transmitted Infections ,Minority Health ,Women's Health ,Neurosciences ,Biomedical Imaging ,Infectious Diseases ,Health Disparities ,Neurological ,Infection ,Adult ,Alleles ,Antineoplastic Agents ,Apolipoprotein E4 ,Basal Ganglia ,Cerebellum ,Cerebral Cortex ,Cerebral Ventricles ,Cohort Studies ,Female ,Gene Expression ,Genotype ,Gray Matter ,HIV Infections ,Humans ,Magnetic Resonance Imaging ,Male ,Middle Aged ,Neuroimaging ,Risk Factors ,White Matter ,Genetics ,Magnetic resonance spectroscopy ,Brain volumetrics ,CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) Group ,Clinical Sciences ,Virology ,Clinical sciences ,Medical microbiology - Abstract
Previous neuroimaging studies suggest a negative relationship between the apolipoprotein (ApoE) ε4 allele and brain integrity in human immunodeficiency virus (HIV)-infected (HIV+) individuals, although the presence of this relationship across adulthood remains unclear. The purpose of this study is to clarify the discrepancies using a large, diverse group of HIV+ individuals and multiple imaging modalities sensitive to HIV. The association of ApoE ε4 with structural neuroimaging and magnetic resonance spectroscopy (MRS) was examined in 237 HIV+ individuals in the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study. Cortical and subcortical gray matter, abnormal and total white matter, ventricles, sulcal cerebrospinal fluid (CSF), and cerebellar gray matter, white matter, and CSF volumes, and MRS concentrations of myo-inositol, creatine, N-acetyl-aspartate, and choline in the frontal white matter (FWM), frontal gray matter (FGM), and basal ganglia were examined. Secondary analyses explored this relationship separately in individuals ≥50 years old (n = 173) and
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- 2016
39. Neurocognitive Change in the Era of HIV Combination Antiretroviral Therapy: The Longitudinal CHARTER Study
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Heaton, Robert K, Franklin, Donald R, Deutsch, Reena, Letendre, Scott, Ellis, Ronald J, Casaletto, Kaitlin, Marquine, Maria J, Woods, Steven P, Vaida, Florin, Atkinson, J Hampton, Marcotte, Thomas D, McCutchan, J Allen, Collier, Ann C, Marra, Christina M, Clifford, David B, Gelman, Benjamin B, Sacktor, Ned, Morgello, Susan, Simpson, David M, Abramson, Ian, Gamst, Anthony C, Fennema-Notestine, Christine, Smith, David M, Grant, Igor, Franklin, Donald, Alexander, Terry, Capparelli, Edmund, Woods, Steven Paul, Dawson, Matthew, Taylor, Michael J, Theilmann, Rebecca, Cushman, Clint, Marquie-Beck, Jennifer, McArthur, Justin, Rogalski, Vincent, Simpson, David, Mintz, Letty, Toperoff, Will, Collier, Ann, Marra, Christina, Jones, Trudy, Gelman, Benjamin, Head, Eleanor, Clifford, David, Al-Lozi, Muhammad, and Teshome, Mengesha
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Medical Microbiology ,Biomedical and Clinical Sciences ,Brain Disorders ,Mental Health ,Infectious Diseases ,HIV/AIDS ,Clinical Research ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Infection ,Good Health and Well Being ,Adult ,Cognition Disorders ,Comorbidity ,Female ,HIV Infections ,Humans ,Longitudinal Studies ,Male ,Middle Aged ,cognitive change ,HIV ,antiretroviral therapy ,comorbidities ,CHARTER Group ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Clinical sciences - Abstract
BackgroundHuman immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) can show variable clinical trajectories. Previous longitudinal studies of HAND typically have been brief, did not use adequate normative standards, or were conducted in the context of a clinical trial, thereby limiting our understanding of incident neurocognitive (NC) decline and recovery.MethodsWe investigated the incidence and predictors of NC change over 16-72 (mean, 35) months in 436 HIV-infected participants in the CNS HIV Anti-Retroviral Therapy Effects Research cohort. Comprehensive laboratory, neuromedical, and NC assessments were obtained every 6 months. Published, regression-based norms for NC change were used to generate overall change status (decline vs stable vs improved) at each study visit. Survival analysis was used to examine the predictors of time to NC change.ResultsNinety-nine participants (22.7%) declined, 265 (60.8%) remained stable, and 72 (16.5%) improved. In multivariable analyses, predictors of NC improvements or declines included time-dependent treatment status and indicators of disease severity (current hematocrit, albumin, total protein, aspartate aminotransferase), and baseline demographics and estimated premorbid intelligence quotient, non-HIV-related comorbidities, current depressive symptoms, and lifetime psychiatric diagnoses (overall model P < .0001).ConclusionsNC change is common in HIV infection and appears to be driven by a complex set of risk factors involving HIV disease, its treatment, and comorbid conditions.
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- 2015
40. Post-acute sensory neurological sequelae in patients with severe acute respiratory syndrome coronavirus 2 infection: the COVID-PN observational cohort study
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Odozor, Chioma U., Kannampallil, Thomas, Ben Abdallah, Arbi, Roles, Kristen, Burk, Carrie, Warner, Benjamin C., Alaverdyan, Harutyun, Clifford, David B., Piccirillo, Jay F., and Haroutounian, Simon
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- 2022
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41. Downstream Biomarker Effects of Gantenerumab or Solanezumab in Dominantly Inherited Alzheimer Disease: The DIAN-TU-001 Randomized Clinical Trial.
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Wagemann, Olivia, Liu, Haiyan, Wang, Guoqiao, Shi, Xinyu, Bittner, Tobias, Scelsi, Marzia A., Farlow, Martin R., Clifford, David B., Supnet-Bell, Charlene, Santacruz, Anna M., Aschenbrenner, Andrew J., Hassenstab, Jason J., Benzinger, Tammie L. S., Gordon, Brian A., Coalier, Kelley A., Cruchaga, Carlos, Ibanez, Laura, Perrin, Richard J., Xiong, Chengjie, and Li, Yan
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- 2024
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42. Examining amyloid reduction as a surrogate endpoint through latent class analysis using clinical trial data for dominantly inherited Alzheimer's disease.
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Wang, Guoqiao, Li, Yan, Xiong, Chengjie, Benzinger, Tammie L. S., Gordon, Brian A., Hassenstab, Jason, Aschenbrenner, Andrew J., McDade, Eric, Clifford, David B., Libre‐Guerra, Jorge J., Shi, Xinyu, Mummery, Catherine J., van Dyck, Christopher H., Lah, James J., Honig, Lawrence S., Day, Gregg, Ringman, John M., Brooks, William S., Fox, Nick C., and Suzuki, Kazushi
- Abstract
INTRODUCTION: Increasing evidence suggests that amyloid reduction could serve as a plausible surrogate endpoint for clinical and cognitive efficacy. The double‐blind phase 3 DIAN‐TU‐001 trial tested clinical and cognitive declines with increasing doses of solanezumab or gantenerumab. METHODS: We used latent class (LC) analysis on data from the Dominantly Inherited Alzheimer Network Trials Unit 001 trial to test amyloid positron emission tomography (PET) reduction as a potential surrogate biomarker. RESULTS: LC analysis categorized participants into three classes: amyloid no change, amyloid reduction, and amyloid growth, based on longitudinal amyloid Pittsburgh compound B PET standardized uptake value ratio data. The amyloid‐no‐change class was at an earlier disease stage for amyloid amounts and dementia. Despite similar baseline characteristics, the amyloid‐reduction class exhibited reductions in the annual decline rates compared to the amyloid‐growth class across multiple biomarker, clinical, and cognitive outcomes. DISCUSSION: LC analysis indicates that amyloid reduction is associated with improved clinical outcomes and supports its use as a surrogate biomarker in clinical trials. Highlights: We used latent class (LC) analysis to test amyloid reduction as a surrogate biomarker.Despite similar baseline characteristics, the amyloid‐reduction class exhibited remarkably better outcomes compared to the amyloid‐growth class across multiple measures.LC analysis proves valuable in testing amyloid reduction as a surrogate biomarker in clinical trials lacking significant treatment effects. [ABSTRACT FROM AUTHOR]
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- 2024
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43. Persistent CSF but not plasma HIV RNA is associated with increased risk of new-onset moderate-to-severe depressive symptoms; a prospective cohort study
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Hammond, Edward R, Crum, Rosa M, Treisman, Glenn J, Mehta, Shruti H, Clifford, David B, Ellis, Ronald J, Gelman, Benjamin B, Grant, Igor, Letendre, Scott L, Marra, Christina M, Morgello, Susan, Simpson, David M, Mcarthur, Justin C, and for the CHARTER Group
- Subjects
Medical Microbiology ,Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Research ,Infectious Diseases ,Brain Disorders ,Mental Illness ,Serious Mental Illness ,Depression ,HIV/AIDS ,Sexually Transmitted Infections ,Minority Health ,Mental Health ,Infection ,Adult ,Anti-HIV Agents ,Antiretroviral Therapy ,Highly Active ,Biomarkers ,Depressive Disorder ,Major ,Female ,HIV Infections ,Humans ,Male ,Medication Adherence ,Middle Aged ,Prognosis ,Prospective Studies ,RNA ,Viral ,Severity of Illness Index ,Viral load ,Cerebrospinal fluid ,Psychiatry ,CHARTER Group ,Neurosciences ,Virology ,Clinical sciences ,Medical microbiology - Abstract
Major depressive disorder is the most common neuropsychiatric complication in human immunodeficiency virus (HIV) infections and is associated with worse clinical outcomes. We determined if detectable cerebrospinal fluid (CSF) HIV ribonucleic acid (RNA) at threshold ≥50 copies/ml is associated with increased risk of depression. The CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) cohort is a six-center US-based prospective cohort with bi-annual follow-up of 674 participants. We fit linear mixed models (N = 233) and discrete-time survival models (N = 154; 832 observations) to evaluate trajectories of Beck Depression Inventory (BDI) II scores and the incidence of new-onset moderate-to-severe depressive symptoms (BDI ≥ 17) among participants on combination antiretroviral therapy (cART), who were free of depression at study entry and received a minimum of three CSF examinations over 2496 person-months follow-up. Detectable CSF HIV RNA (threshold ≥50 copies/ml) at any visit was associated with a 4.7-fold increase in new-onset depression at subsequent visits adjusted for plasma HIV RNA and treatment adherence; hazard ratio (HR) = 4.76, (95 % CI 1.58-14.3); P = 0.006. Depression (BDI) scores were 2.53 points higher (95 % CI 0.47-4.60; P = 0.02) over 6 months if CSF HIV RNA was detectable at a prior study visit in fully adjusted models including age, sex, race, education, plasma HIV RNA, duration and adherence of CART, and lifetime depression diagnosis by Diagnostic Statistical Manual (DSM-IV) criteria. Persistent CSF but not plasma HIV RNA is associated with an increased risk for new-onset depression. Further research evaluating the role of immune activation and inflammatory markers may improve our understanding of this association.
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- 2016
44. The effect of microbial colonization on the host proteome varies by gastrointestinal location.
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Lichtman, Joshua, Alsentzer, Emily, Jaffe, Mia, Sprockett, Daniel, Masutani, Evan, Ikwa, Elvis, Clifford, David, Huang, Bevan, Sonnenburg, Justin, Huang, Kerwyn, Elias, Joshua, and Fragiadakis, Gabriela
- Subjects
Animals ,Cecum ,Cluster Analysis ,Feces ,Gastrointestinal Microbiome ,Gastrointestinal Tract ,Ileum ,Jejunum ,Mass Spectrometry ,Mice ,Proteome ,Stomach - Abstract
Endogenous intestinal microbiota have wide-ranging and largely uncharacterized effects on host physiology. Here, we used reverse-phase liquid chromatography-coupled tandem mass spectrometry to define the mouse intestinal proteome in the stomach, jejunum, ileum, cecum and proximal colon under three colonization states: germ-free (GF), monocolonized with Bacteroides thetaiotaomicron and conventionally raised (CR). Our analysis revealed distinct proteomic abundance profiles along the gastrointestinal (GI) tract. Unsupervised clustering showed that host protein abundance primarily depended on GI location rather than colonization state and specific proteins and functions that defined these locations were identified by random forest classifications. K-means clustering of protein abundance across locations revealed substantial differences in host protein production between CR mice relative to GF and monocolonized mice. Finally, comparison with fecal proteomic data sets suggested that the identities of stool proteins are not biased to any region of the GI tract, but are substantially impacted by the microbiota in the distal colon.
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- 2016
45. Anemia and Red Blood Cell Indices Predict HIV-Associated Neurocognitive Impairment in the Highly Active Antiretroviral Therapy Era
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Kallianpur, Asha R, Wang, Quan, Jia, Peilin, Hulgan, Todd, Zhao, Zhongming, Letendre, Scott L, Ellis, Ronald J, Heaton, Robert K, Franklin, Donald R, Barnholtz-Sloan, Jill, Collier, Ann C, Marra, Christina M, Clifford, David B, Gelman, Benjamin B, McArthur, Justin C, Morgello, Susan, Simpson, David M, McCutchan, JA, and Grant, Igor
- Subjects
Medical Microbiology ,Biomedical and Clinical Sciences ,Acquired Cognitive Impairment ,Infectious Diseases ,Brain Disorders ,Neurosciences ,HIV/AIDS ,Hematology ,Clinical Research ,Dementia ,Neurodegenerative ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Infection ,Good Health and Well Being ,AIDS Dementia Complex ,Adult ,Anemia ,Anti-HIV Agents ,Antiretroviral Therapy ,Highly Active ,Cohort Studies ,Cross-Sectional Studies ,Erythrocyte Count ,Erythrocyte Indices ,Female ,HIV Infections ,Humans ,Male ,Middle Aged ,Multivariate Analysis ,Odds Ratio ,Predictive Value of Tests ,Risk Factors ,human immunodeficiency virus ,anemia ,red blood cell indices ,mitochondrial dysfunction ,HIV-associated neurocognitive disorder ,neurocognitive impairment ,iron metabolism ,CHARTER Study Group ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundAnemia has been linked to adverse human immunodeficiency virus (HIV) outcomes, including dementia, in the era before highly active antiretroviral therapy (HAART). Milder forms of HIV-associated neurocognitive disorder (HAND) remain common in HIV-infected persons, despite HAART, but whether anemia predicts HAND in the HAART era is unknown.MethodsWe evaluated time-dependent associations of anemia and cross-sectional associations of red blood cell indices with neurocognitive impairment in a multicenter, HAART-era HIV cohort study (N = 1261), adjusting for potential confounders, including age, nadir CD4(+) T-cell count, zidovudine use, and comorbid conditions. Subjects underwent comprehensive neuropsychiatric and neuromedical assessments.ResultsHAND, defined according to standardized criteria, occurred in 595 subjects (47%) at entry. Mean corpuscular volume and mean corpuscular hemoglobin were positively associated with the global deficit score, a continuous measure of neurocognitive impairment (both P < .01), as well as with all HAND, milder forms of HAND, and HIV-associated dementia in multivariable analyses (all P < .05). Anemia independently predicted development of HAND during a median follow-up of 72 months (adjusted hazard ratio, 1.55; P < .01).ConclusionsAnemia and red blood cell indices predict HAND in the HAART era and may contribute to risk assessment. Future studies should address whether treating anemia may help to prevent HAND or improve cognitive function in HIV-infected persons.
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- 2016
46. Long-term efavirenz use is associated with worse neurocognitive functioning in HIV-infected patients
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Ma, Qing, Vaida, Florin, Wong, Jenna, Sanders, Chelsea A, Kao, Yu-ting, Croteau, David, Clifford, David B, Collier, Ann C, Gelman, Benjamin B, Marra, Christina M, McArthur, Justin C, Morgello, Susan, Simpson, David M, Heaton, Robert K, Grant, Igor, Letendre, Scott L, and for the CHARTER Group
- Subjects
Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Sexually Transmitted Infections ,Women's Health ,Behavioral and Social Science ,Mental Health ,Infectious Diseases ,Hepatitis ,Hepatitis - C ,Liver Disease ,Clinical Research ,Digestive Diseases ,HIV/AIDS ,Neurosciences ,Emerging Infectious Diseases ,6.1 Pharmaceuticals ,Infection ,Good Health and Well Being ,Adult ,Alkynes ,Anti-HIV Agents ,Benzoxazines ,CD4 Lymphocyte Count ,CD4-Positive T-Lymphocytes ,Cognitive Dysfunction ,Coinfection ,Cyclopropanes ,Drug Therapy ,Combination ,Executive Function ,Female ,HIV Infections ,HIV-1 ,Hepacivirus ,Hepatitis C ,Humans ,Lopinavir ,Male ,Memory ,Middle Aged ,Neuropsychological Tests ,Ritonavir ,Verbal Learning ,Long-termantiretroviral therapy ,Neurocognitive function ,Efavirenz ,Lopinavir/ritonavir ,Neurotoxicity ,Hepatitis C virus coinfection ,CHARTER Group ,Long-term antiretroviral therapy ,Clinical Sciences ,Virology ,Clinical sciences ,Medical microbiology - Abstract
Neurocognitive (NC) complications continue to afflict a substantial proportion of HIV-infected people taking effective antiretroviral therapy (ART). One contributing mechanism for this is antiretroviral neurotoxicity. Efavirenz (EFV) is associated with short-term central nervous system (CNS) toxicity, but less is known about its long-term effects. Our objective was to compare NC functioning with long-term use of EFV to that of a comparator, lopinavir-ritonavir (LPV/r), in a cohort of well-characterized adults. Four hundred forty-five patients were selected from the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) cohort based on their use of either EFV (n = 272, mean duration 17.9 months) or LPV/r (n = 173, mean duration 16.4 months) and the lack of severe NC comorbidities. All patients had undergone standardized comprehensive NC testing. Univariable and multivariable analyses to predict NC outcomes were performed. Compared with LPV/r users, EFV users were more likely to be taking their first ART regimen (p
- Published
- 2016
47. Lower CSF Aβ is Associated with HAND in HIV-Infected Adults with a Family History of Dementia.
- Author
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Fazeli, Pariya L, Moore, David J, Franklin, Donald R, Umlauf, Anya, Heaton, Robert K, Collier, Ann C, Marra, Christina M, Clifford, David B, Gelman, Benjamin B, Sacktor, Ned C, Morgello, Susan, Simpson, David M, McCutchan, John A, Grant, Igor, and Letendre, Scott L
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Health Services and Systems ,Health Sciences ,Acquired Cognitive Impairment ,Brain Disorders ,Clinical Research ,Neurosciences ,2.1 Biological and endogenous factors ,Aetiology ,Neurological ,AIDS Dementia Complex ,Adult ,Amyloid beta-Peptides ,Cerebrospinal Fluid ,Cross-Sectional Studies ,Dementia ,Female ,HIV Infections ,Humans ,Male ,Middle Aged ,HIV ,dementia ,biomarkers ,cerebrospinal fluid ,family history ,neurocognitive impairment ,Medical and Health Sciences ,Virology ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundBoth family history of dementia (FHD) and lower levels of Aβ-42 are indepentently associated with worse neurocognitive functioning in HIVinfected patients.ObjectiveTo examine the relationships between cerebrospinal fluid (CSF) Aβ-42 and FHD with HIV-associated neurocognitive disorders (HAND).MethodsOne hundred eighty-three HIV+ adults underwent neuropsychological and neuromedical assessments, and determination of CSF Aβ-42 concentration and FHD (defined as a self-reported first or second-degree relative with a dementia diagnosis). Univariate analyses and multivariable logistic regressions were used.ResultsFHD was not associated with HAND (p = 0.24); however, CSF Aβ-42 levels were lower (p = 0.03) in the HAND group, but were not associated with FHD (p = 0.89). Multivariable models showed a main effect of CSF Aβ-42 (p = 0.03) and a trend-level (p = 0.06) interaction between FHD and CSF Aβ-42, such that lower CSF Aβ-42 was associated with HAND in those with FHD (p < 0.01) compared to those without FHD (p = 0.83). An analysis in those with follow-up data showed that higher baseline CSF Aβ-42 was associated with lower risk of neurocognitive decline (p = 0.02). While we did not find an FHD X CSF Aβ-42 interaction (p = 0.83), when analyses were stratified by FHD, lower CSF Aβ-42 was associated at the trend-level with neurocognitive decline in the FHD group (p = 0.08) compared to the no FHD group (p = 0.15).ConclusionFHD moderates the relationship between of CSF Aβ-42 and HAND. The findings highlight the complexities in interpreting the relationships between biomarkers of age-related neurodegeneration and HAND.
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- 2016
48. Gender inequalities in unpaid public work: Retention, stratification and segmentation in the volunteer leadership of charities in England and Wales
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Clifford, David, primary
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- 2023
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- View/download PDF
49. International charitable connections: Variation in the countries of operation of overseas charities
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McDonnell, Diarmuid, primary and Clifford, David, additional
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- 2023
- Full Text
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50. Mycobacterium haemophilum related myelitis in geographically linked cases
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Samudralwar, Rohini D., primary, Bailey, Thomas C., additional, Vellimana, Ananth K., additional, Wright, Neill M., additional, and Clifford, David B., additional
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- 2023
- Full Text
- View/download PDF
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