The Influence of HLA on HIV-Associated Neurocognitive Impairment in Anhui, China

HLA-DR*04 was identified as a predictor of HIV-Associated neurocognitive disorder (HAND), low CD4 T-cell responses to HIV, and low plasma HIV RNA levels in a U.S. cohort. We hypothesized that low CD4 T-cell activation leads to poor immune control of HIV in the CNS, predisposing to HAND, but also provided fewer target (activated CD4 T-cells) for HIV replication. To assess the consistency of these HLA Class II associations in a new cohort and extend analysis to HLA Class I, HLA types, neurocognitive, and virologic status were examined in a cohort of former plasma donors in China.178 HIV infected individuals in Anhui China, were HLA typed and underwent neurocognitive evaluations (using locally standardized norms), neuromedical, treatment and virologic assessments at baseline and at 12 months.HLA DR*04 was associated with a higher rate of baseline neurocognitive impairment (p = 0.04), neurocognitive decline (p = 0.04), and lower levels of HIV RNA in plasma (p = 0.05). HLA Class I alleles (B*27,57,58,A*03,33) that specify a CD8 T-cell response to conserved HIV sequences were neuroprotective, associated with less impairment at baseline (p = 0.037), at month 012 (p = 0.013) and less neurocognitive decline (p = 0.023) in the interval. Consistent with the theory that effective CD8 T-cell responses require CD4 T-cell support, the HLA DR*04 allele reduced the neuroprotective effect of the Class I alleles. The presence of HLA-DR*04 and the Alzheimer associated allele ApoE4 in the same individual had a synergistic negative effect on cognition (p = 0.003).Despite major background differences between U.S. and Anhui China cohorts, HLA DR*04 predicted neurocognitive impairment and lower plasma HIV RNA levels in both populations. HLA Class I alleles associated with CD8 T-cell control of HIV were associated with protection from HAND, but protection was reduced in the presence of HLA-DR*04

A multicenter assessment of interreader reliability of LI-RADS version 2018 for MRI and CT

Background: Various limitations have impacted research evaluating reader agreement for Liver Imaging-Reporting and Data System (LI-RADS). Purpose: To assess reader agreement of LI-RADS in an international multi-center, multireader setting using scrollable images. Materials and Methods: This retrospective study used de-identified clinical multiphase CT and MRI examinations and reports with at least one untreated observation from six institutions and three countries; only qualifying examinations were submitted. Examination dates were October 2017 – August 2018 at the coordinating center. One untreated observation per examination was randomly selected using observation identifiers, and its clinically assigned features were extracted from the report. The corresponding LI-RADS v2018 category was computed as a re-scored clinical read. Each examination was randomly assigned to two of 43 research readers who independently scored the observation. Agreement for an ordinal modified four-category LI-RADS scale (LR-1/2, LR-3, LR-4, LR-5/M/tumor in vein) was computed using intra-class correlation coefficients (ICC). Agreement was also computed for dichotomized malignancy (LR-4/LR5/LR-M/LR-tumor in vein), LR-5, and LR-M. Agreement was compared between researchversus-research reads and research-versus-clinical reads. Results: 484 patients (mean age, 62 years ±10 [SD]; 156 women; 93 CT, 391 MRI) were included. ICCs for ordinal LI-RADS, dichotomized malignancy, LR-5, and LR-M were 0.68 (95% CI: 0.62, 0.74), 0.63 (95% CI: 0.56, 0.71), 0.58 (95% CI: 0.50, 0.66), and 0.46 (95% CI: 0.31, 0.61) respectively. Research-versus-research reader agreement was higher than research-versus-clinical agreement for modified four-category LI-RADS (ICC, 0.68 vs. 0.62, P = .03) and for dichotomized malignancy (ICC, 0.63 vs. 0.53, P = .005), but not for LR-5 (P = .14) or LR-M (P = .94). Conclusion: There was moderate agreement for Liver Imaging-Reporting and Data System v2018 overall. For some comparisons, research-versus-research reader agreement was higher than research-versus-clinical reader agreement, indicating differences between the clinical and research environments that warrant further study

HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors

Combination antiretroviral therapy (CART) has greatly reduced medical morbidity and mortality with HIV infection, but high rates of HIV-associated neurocognitive disorders (HAND) continue to be reported. Because large HIV-infected (HIV+) and uninfected (HIV−) groups have not been studied with similar methods in the pre-CART and CART eras, it is unclear whether CART has changed the prevalence, nature, and clinical correlates of HAND. We used comparable methods of subject screening and assessments to classify neurocognitive impairment (NCI) in large groups of HIV + and HIV − participants from the pre-CART era (1988–1995; N = 857) and CART era (2000–2007; N = 937). Impairment rate increased with successive disease stages (CDC stages A, B, and C) in both eras: 25%, 42%, and 52% in pre-CART era and 36%, 40%, and 45% in CART era. In the medically asymptomatic stage (CDC-A), NCI was significantly more common in the CART era. Low nadir CD4 predicted NCI in both eras, whereas degree of current immunosuppression, estimated duration of infection, and viral suppression in CSF (on treatment) were related to impairment only pre-CART. Pattern of NCI also differed: pre-CART had more impairment in motor skills, cognitive speed, and verbal fluency, whereas CART era involved more memory (learning) and executive function impairment. High rates of mild NCI persist at all stages of HIV infection, despite improved viral suppression and immune reconstitution with CART. The consistent association of NCI with nadir CD4 across eras suggests that earlier treatment to prevent severe immunosuppression may also help prevent HAND. Clinical trials targeting HAND prevention should specifically examine timing of ART initiation

A Comparison of E-Cigarette Use Patterns and Smoking Cessation Behavior among Vapers by Primary Place of Purchase

Background: E-cigarettes are purchased through multiple channels, including general retail, online, and specialty smoke and vape shops. We examine how e-cigarette users’ primary purchase place relates to e-cigarette use and smoking cessation behaviors. Methods: Probability-based samples of the U.S. population who were current e-cigarette users were surveyed in 2014 (N = 879) and 2016 (N = 743), with responses combined for most analyses. E-cigarette use and smoking cessation behaviors were compared across users’ primary purchase place. Results: Higher percentages of vape shop (59.1%) and internet (42.9%) customers were current daily users of e-cigarettes compared to retail (19.7%) and smoke shop (23.2%) customers (p-values < 0.001). Higher percentages of vape shop (40.2%) and internet (35.1%) customers were also former smokers, compared to 17.7% of retail and 19.3% of smoke shop customers (p’s < 0.001). Among those smoking 12 months prior to survey, smoking cessation rates were higher for vape shop (22.2%) and internet customers (22.5%) than for retail customers (10.7%, p = 0.010 and p = 0.022, respectively), even though retail customers were more likely to use FDA-approved smoking cessation aids. The percentage of customers purchasing from vape shops increased from 20.4% in 2014 to 37.6% in 2016, surpassing general retail (27.7%) as the most likely channel in 2016. Conclusions: E-cigarette customers differed in significant ways by channels of purchase, most notably in their smoking cessation behaviors. Previous population studies have relied mostly on retail channel data, which accounted for less than 30% of all products sold by 2016. Future studies of e-cigarette use should consider a broader set of channels

Comparison of smoking cessation between education groups: findings from 2 US National Surveys over 2 decades.

ObjectivesWe examined smoking cessation rate by education and determined how much of the difference can be attributed to the rate of quit attempts and how much to the success of these attempts.MethodsWe analyzed data from the National Health Interview Survey (NHIS, 1991-2010) and the Tobacco Use Supplement to the Current Population Survey (TUS-CPS, 1992-2011). Smokers (≥ 25 years) were divided into lower- and higher-education groups (≤ 12 years and >12 years).ResultsA significant difference in cessation rate between the lower- and the higher-education groups persisted over the last 2 decades. On average, the annual cessation rate for the former was about two thirds that of the latter (3.5% vs 5.2%; P<.001, for both NHIS and TUS-CPS). About half the difference in cessation rate can be attributed to the difference in quit attempt rate and half to the difference in success rate.ConclusionsSmokers in the lower-education group have consistently lagged behind their higher-education counterparts in quitting. In addition to the usual concern about improving their success in quitting, tobacco control programs need to find ways to increase quit attempts in this group