Search

This single-institution cross-sectional study aimed to grasp the prevalence and features of neurocognitive dysfunction in HIV-infected hemophilia patients in Japan. We conducted neuropsychological tests and medical examinations in 56 HIV-infected hemophilia patients who received outpatient treatment at the AIDS Clinical Center, National Center for Global Health and Medicine. A total of 388 HIV-infected non-hemophilia patients who received outpatient treatment at the same institution were included as a control group. To investigate sites responsible for neurocognitive dysfunction in HIV-infected hemophilia patients using brain FDG-PET/CT scans, the accumulation of FDG in each brain region was compared. Approximately 50% of HIV-infected hemophilia patients had neurocognitive dysfunction. The prevalence of asymptomatic neurocognitive impairment was high (34%). Neurocognitive dysfunction was associated with educational level in HIV-infected hemophilia patients. In the symptomatic group, hemophilic arthropathy and history of cerebrovascular disorders were associated with neurocognitive dysfunction. Left temporal lobe function was reduced in the symptomatic group. [ABSTRACT FROM AUTHOR]

Background: Oil and gas development emits known hematological carcinogens, such as benzene, and increasingly occurs in residential areas. We explored whether residential proximity to oil and gas development was associated with risk for hematologic cancers using a registry-based case-control study design. Methods: Participants were 0–24 years old, living in rural Colorado, and diagnosed with cancer between 2001–2013. For each child in our study, we calculated inverse distance weighted (IDW) oil and gas well counts within a 16.1-kilometer radius of residence at cancer diagnosis for each year in a 10 year latency period to estimate density of oil and gas development. Logistic regression, adjusted for age, race, gender, income, and elevation was used to estimate associations across IDW well count tertiles for 87 acute lymphocytic leukemia (ALL) cases and 50 non-Hodgkin lymphoma (NHL) cases, compared to 528 controls with non-hematologic cancers. Findings: Overall, ALL cases 0–24 years old were more likely to live in the highest IDW well count tertiles compared to controls, but findings differed substantially by age. For ages 5–24, ALL cases were 4.3 times as likely to live in the highest tertile, compared to controls (95% CI: 1.1 to 16), with a monotonic increase in risk across tertiles (trend p-value = 0.035). Further adjustment for year of diagnosis increased the association. No association was found between ALL for children aged 0–4 years or NHL and IDW well counts. While our study benefited from the ability to select cases and controls from the same population, use of cancer-controls, the limited number of ALL and NHL cases, and aggregation of ages into five year ranges, may have biased our associations toward the null. In addition, absence of information on O&G well activities, meteorology, and topography likely reduced temporal and spatial specificity in IDW well counts. Conclusion: Because oil and gas development has potential to expose a large population to known hematologic carcinogens, further study is clearly needed to substantiate both our positive and negative findings. Future studies should incorporate information on oil and gas development activities and production levels, as well as levels of specific pollutants of interest (e.g. benzene) near homes, schools, and day care centers; provide age-specific residential histories; compare cases to controls without cancer; and address other potential confounders, and environmental stressors. [ABSTRACT FROM AUTHOR]

Background: HIV-associated neurocognitive disorders (HAND) are widely present among people living with HIV. Especially its milder forms, asymptomatic neurocognitive impairment (ANI) and mild neurocognitive disorder (MND), remain highly prevalent worldwide. Diagnosing these conditions is subject to a time and resource consuming neuropsychological assessment. Selecting patients at a higher risk of cognitive impairment by using a simple but effective screening tool helps to organise access to further neuropsychological diagnosis. The International HIV Dementia Scale (IHDS) has until now been a well-established screening tool in African and American countries, however these populations’ demographics defer significantly from ours, so using the same parameters could be ineffective. Objectives: To calculate the prevalence of this condition among people attending an HIV outpatient clinic in Berlin and to validate the use of the IHDS as a screening tool for HAND in a German-speaking population. Methods: We screened 480 HIV-infected patients using the IHDS, 89% of them were on a stable antiretroviral treatment. Ninety of them completed a standardised neuropsychological battery of tests and a specific cognitive complaints questionnaire. The same procedure was applied to a control group of 30 HIV-negative participants. HAND diagnosis was established according to the Frascati criteria. Results: The overall prevalence of HAND in our cohort was 43% (20% ANI, 17% MND and 6% HIV-associated dementia). The optimal cut-off on the IHDS for detecting HAND cases was set at 11 and achieved both a sensitivity and a specificity of 80%. When specifically screening for the more severe form of HAND, HIV-associated dementia, a cut-off value of 10 offered an increase in both sensitivity (94%) and specificity (86%). The Youden Index for diagnostic accuracy was 0.6 and 0.8, respectively. Conclusions: The prevalence of HAND was comparable to the reported by recent studies performed in countries with a similar economic development. The study confirms the IHDS to be a useful HAND screening tool in primary care settings and establishes new recommendations for its use in German-speaking countries. [ABSTRACT FROM AUTHOR]

We compared the proliferation of neonatal and adult airway smooth muscle cells (ASMC) with no/moderate lung disease, in glucose- (energy production by glycolysis) or glucose-free medium (ATP production from mitochondrial oxidative phosphorylations only), in response to 10% fetal calf serum (FCS) and PDGF-AA. In the presence of glucose, cell counts were significantly greater in neonatal vs. adult ASMC. Similarly, neonatal ASMC DNA synthesis in 10% FCS and PDGF-AA, and [Ca2+]i responses in the presence of histamine were significantly enhanced vs. adults. In glucose-free medium, cell proliferation was preserved in neonatal cells, unlike in adult cells, with concomitant increased porin (an indicator of mitochondrial activity) protein expression. Compared to adults, stimulated neonatal human ASMC are in a rapid and robust proliferative phase and have the capacity to respond disproportionately under abnormal environmental conditions, through increased mitochondrial biogenesis and altered calcium homeostasis. [ABSTRACT FROM AUTHOR]

Objective: To compare two definitions of neurocognitive impairment (NCI) in a large clinical trial of effectively-treated HIV-infected adults at baseline. Methods: Hopkins Verbal Learning test-Revised (HVLT-R), Colour Trail (CTT) and Grooved Pegboard (GPT) tests were applied exploring five cognitive domains. Raw scores were transformed into Z-scores and NCI defined as summary NPZ-5 score one standard deviation below the mean of the normative dataset (i.e. <−1SD) or Z-scores <−1SD in at least two individual domains (categorical scale). Principal component analysis (PCA) was performed to explore the contribution of individual tests to the total variance. Results: Mean NPZ-5 score was −0.72 (SD 0.98) and 178/548 (32%) participants had NPZ-5 scores <−1SD. When impairment was defined as <−1SD in at least two individual tests, 283 (52%) patients were impaired. Strong correlations between the two components of the HVLT-R test (learning/recall) (r = 0.73), and the CTT and (attention/executive functioning) (r = 0.66) were observed. PCA showed a clustering with three components accounting for 88% of the total variance. When patients who scored <−1SD only in two correlated tests were considered as not impaired, prevalence of NCI was 43%. When correlated test scores were averaged, 36% of participants had NPZ-3 scores <−1SD and 32% underperformed in at least two individual tests. Conclusion: Controlling for differential contribution of individual test-scores on the overall performance and the level of correlation between components of the test battery used appear to be important when testing cognitive function. These two factors are likely to affect both summary scores and categorical scales in defining cognitive impairment. Trial registration: EUDRACT: 2007-006448-23 and ISRCTN04857074. [ABSTRACT FROM AUTHOR]

Background: Little is known about the prevalence and burden of HIV associated neurocognitive disorder (HAND) among patients on combination antiretroviral therapy (cART) in sub-Saharan Africa. We estimated the prevalence of HAND in adult Malawians on cART and investigated the relationship between HAND and adherence to cART. Methods: HIV positive adults in Blantyre, Malawi underwent a full medical history, neurocognitive test battery, depression score, Karnofsky Performance Score and adherence assessment. The Frascati criteria were used to diagnose HAND and the Global Deficit Score (GDS) was also assessed. Blood was drawn for CD4 count and plasma nevirapine and efavirenz concentrations. HIV negative adults were recruited from the HIV testing clinic to provide normative scores for the neurocognitive battery. Results: One hundred and six HIV positive patients, with median (range) age 39 (18–71) years, 73% female and median (range) CD4 count 323.5 (68–1039) cells/µl were studied. Symptomatic neurocognitive impairment was present in 15% (12% mild neurocognitive disorder [MND], 3% HIV associated dementia [HAD]). A further 55% fulfilled Frascati criteria for asymptomatic neurocognitive impairment (ANI); however factors other than neurocognitive impairment could have confounded this estimate. Neither the symptomatic (MND and HAD) nor asymptomatic (ANI) forms of HAND were associated with subtherapeutic nevirapine/efavirenz concentrations, adjusted odds ratio 1.44 (CI. 0.234, 8.798; p = 0.696) and aOR 0.577 (CI. 0.09, 3.605; p = 0.556) respectively. All patients with subtherapeutic nevirapine/efavirenz levels had a GDS of less than 0.6, consistent with normal neurocognition. Discussion/Conclusion: Fifteen percent of adult Malawians on cART had a diagnosis of MND or HAD. Subtherapeutic drug concentrations were found exclusively in patients with normal neurocognitive function suggesting HAND did not affect cART adherence. Further study of HAND requires more robust locally derived normative neurocognitive values and determination of the clinical relevance of ANI. [ABSTRACT FROM AUTHOR]