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  • Clifford, David B.  (2)
  • Collier, Ann C.  (2)
  • Letendre, Scott L.  (2)
  • Sacktor, Ned  (2)
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  • 1
    Online Resource
    Online Resource
    Genome‐wide association study of HIV‐associated neurocognitive disorder (HAND): A CHARTER group study
    Wiley ; 2017
    In:  American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Vol. 174, No. 4 ( 2017-06), p. 413-426
    Details
    In: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, Wiley, Vol. 174, No. 4 ( 2017-06), p. 413-426
    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  〈  0.5, and GDS as a continuous variable) and Frascati HAND definitions that incorporate assessment of functional impairment by self‐report and performance‐based criteria. Genotype data were obtained using the Affymetrix Human SNP Array 6.0 platform. Multivariable logistic or linear regression‐based association tests were performed for GDS‐defined NCI and HAND. GWAS results did not reveal SNPs meeting the genome‐wide significance threshold (5.0 × 10 −8 ) for GDS‐defined NCI or HAND. For binary GDS, the most significant SNPs were rs6542826 ( P  = 8.1 × 10 −7 ) and rs11681615 (1.2 × 10 −6 ), both located on chromosome 2 in SH3RF3 . The most significant SNP for continuous GDS was rs11157436 ( P  = 1.3 × 10 −7 ) on chromosome 14 in the T‐cell‐receptor alpha locus; three other SNPs in this gene were also associated with binary GDS ( P  ≤ 2.9 × 10 −6 ). This GWAS, conducted among ART‐era participants from a single cohort with robust neurological phenotyping, suggests roles for several biologically plausible loci in HAND that deserve further exploration. © 2017 Wiley Periodicals, Inc.
    Type of Medium: Online Resource
    ISSN: 1552-4841 , 1552-485X
    URL: Issue
    URL: Article
    DOI: 10.1002/ajmg.b.v174.4
    DOI: 10.1002/ajmg.b.32530
    Language: English
    Publisher: Wiley
    Publication Date: 2017
    detail.hit.zdb_id: 2143866-3
    SSG: 12
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    Online Resource
  • 2
    Online Resource
    Online Resource
    Predictors of worsening neuropathy and neuropathic pain after 12 years in people with HIV
    Wiley ; 2020
    In:  Annals of Clinical and Translational Neurology Vol. 7, No. 7 ( 2020-07), p. 1166-1173
    Details
    In: Annals of Clinical and Translational Neurology, Wiley, Vol. 7, No. 7 ( 2020-07), p. 1166-1173
    Abstract: Distal 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. Methods Ambulatory, 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. Results Of 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. Interpretation HIV 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.
    Type of Medium: Online Resource
    ISSN: 2328-9503 , 2328-9503
    URL: Issue
    URL: Article
    DOI: 10.1002/acn3.v7.7
    DOI: 10.1002/acn3.51097
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2740696-9
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