25 research outputs found
Factors Associated with D-Dimer Levels in HIV-Infected Individuals
No full textBackground: Higher plasma D-dimer levels are strong predictors of mortality in HIV+ individuals. The factors associated with D-dimer levels during HIV infection, however, remain poorly understood.
Methods: In this cross-sectional study, participants in three randomized controlled trials with measured D-dimer levels were included (N = 9,848). Factors associated with D-dimer were identified by linear regression. Covariates investigated were: age, gender, race, body mass index, nadir and baseline CD4(+) count, plasma HIV RNA levels, markers of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6]), antiretroviral therapy (ART) use, ART regimens, co-morbidities (hepatitis B/C, diabetes mellitus, prior cardiovascular disease), smoking, renal function (estimated glomerular filtration rate [eGFR] and cystatin C) and cholesterol.
Results: Women from all age groups had higher D-dimer levels than men, though a steeper increase of D-dimer with age occurred in men. Hepatitis B/C co-infection was the only co-morbidity associated with higher D-dimer levels. In this subgroup, the degree of hepatic fibrosis, as demonstrated by higher hyaluronic acid levels, but not viral load of hepatitis viruses, was positively correlated with D-dimer. Other factors independently associated with higher D-dimer levels were black race, higher plasma HIV RNA levels, being off ART at baseline, and increased levels of CRP, IL-6 and cystatin C. In contrast, higher baseline CD4+ counts and higher high-density lipoprotein cholesterol were negatively correlated with D-dimer levels.
Conclusions: D-dimer levels increase with age in HIV+ men, but are already elevated in women at an early age due to reasons other than a higher burden of concomitant diseases. In hepatitis B/C co-infected individuals, hepatic fibrosis, but not hepatitis viral load, was associated with higher D-dimer levels
Haemoglobin and anaemia in the SMART study
No full textBackground: Data from randomized trials on the development of anaemia after interruption of therapy are not well-described. Methods: A total of 2,248 patients from the SMART study were included. We used Cox proportional hazards models to investigate development of new (12 mg/dl for females and <= 14 mg/dl for males) or worsening (8 mg/dl if anaemic at randomization) anaemia and Poisson regression analyses to explore the relationship between anaemia and the development of AIDS, death or non-AIDS events. Results: Overall, 759 patients developed new or worsening anaemia: 420/1,106 (38.0%) in the drug conservation (DC) arm and 339/1127 (30.1%) in the viral suppression (VS) arm (P<0.0001). At 4 months after randomization, patients in the DC arm had a significantly increased risk of developing new or worsening anaemia (adjusted relative hazard 1.56, 95% CI 1.28-1.89). Currently anaemic patients had an increased incidence of AIDS (adjusted incidence rate ratio [IRR] 2.31, 95% CI 1.34-3.98), death (adjusted IRR 2.19, 95% CI 1.23-3.87) and non-AIDS events (adjusted IRR 2.98, 95% CI 2.01-4.40) compared to non-anaemic patients. Conclusions: Patients who interrupted combination anti-retroviral therapy had a higher risk of new or worsening anaemia. Anaemic patients had a higher incidence of AIDS, non-AIDS defining events or deaths, possibly due to deteriorating health and subclinical disease
White matter hyperintensity shape is associated with cognitive functioning - the SMART-MR study
No full textWhite matter hyperintensity (WMH) shape has been associated with the severity of the underlying brain pathology, suggesting it is a potential neuroimaging marker of WMH impact on brain function.In 563 patients with vascular disease (58 +/- 10 years), we examined the relationship between WMH volume, shape, and cognitive functioning. WMH volume and shape were automatically determined on 1.5T brain MRI data. Standardized linear regression analyses estimated the association between WMH volume and shape (concavity index, solidity, convexity, fractal dimension, and eccentricity) and memory and executive functioning, adjusted for age, sex, educational level, and reading ability.Larger WMH volumes were associated with lower executive functioning Z-scores ( b (95%-CI):-0.09 (-0.17;-0.01)). Increased shape complexity of periventricular/confluent WMH associated with lower exec-utive functioning (concavity index + 1SD:-0.13 (-0.20;-0.06); solidity-1SD:-0.09 (-0.17;-0.02)) and lower memory function (fractal dimension + 1SD:-0.10 (-0.18;-0.02)). Of note, the association between concav-ity index and executive functioning was independent of WMH volume (-0.12 (-0.19;-0.04)). Our results suggest that WMH shape contains additional information about WMH burden, not other-wise captured by WMH volume.(c) 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/
Carotid artery stenosis and progression of hemispheric brain atrophy:: the SMART-MR study
No full textIntroduction: It has been hypothesized that carotid artery stenosis (CAS) may lead to greater atrophy of subserved brain regions; however, prospective studies on the impact of CAS on progression of hemispheric brain atrophy are lacking. We examined the association between CAS and progression of hemispheric brain atrophy. Methods: We included 654 patients (57 +/- 9 years) of the SMART-MR study, a prospective cohort study of patients with manifest arterial disease. Patients had baseline CAS duplex measurements and a 1.5T brain MRI at baseline and after 4 years of follow-up. Mean change in hemispheric brain volumes (% of intracranial volume [ICV]) was estimated between baseline and follow-up for left-sided and right-sided CAS across three degrees of stenosis (mild [= 70%]), adjusting for demographics, cerebrovascular risk factors, and brain infarcts. Results: Mean decrease in left and right hemispheric brain volumes was 1.15% ICV and 0.82% ICV, respectively, over 4 years of follow-up. Severe right-sided CAS, compared to mild CAS, was associated with a greater decrease in volume of the left hemisphere (B = -0.49% ICV, 95% CI: -0.86 to -0.13) and more profoundly of the right hemisphere (B = -0.90% ICV, 95% CI: -1.27 to -0.54). This pattern was independent of cerebrovascular risk factors, brain infarcts, and white matter hyperintensities on MRI, and was also observed when accounting for the presence of severe bilateral CAS. Increasing degrees of left-sided CAS, however, was not associated with greater volume loss of the left or right hemisphere. Conclusions: Our data indicate that severe (>= 70%) CAS could represent a risk factor for greater ipsilateral brain volume loss, independent of cerebrovascular risk factors, brain infarcts, or white matter hyperintensities on MRI. Further longitudinal studies in other cohorts are warranted to confirm this novel finding. (C) 2022 The Author(s). Published by S. Karger AG, Base
Structural evaluation of a novel box beam system of Pultruded Fibre Reinforced Polymer shapes
No full textPresented in this thesis is an evaluation of a novel box beam system of Pul-
truded Fibre Reinforced Polymer (PFRP) shapes. The flat-pack modular beam
system consists of separate PFRP flange and web shapes joined together with
a new method of mechanical fastening. It is based on the first generation Star-
tlink building system, conceived by UK engineers in 1999. The Startlink building
system is introduced, and classified within the scope of Modern Methods of Con-
struction (MMC), and its merits are discussed. In the context of MMC a critical
review by the author finds that, although the proposed 1999 generation Startlink
system offers design flexibility, it will probably have a limited market potential.
The novel use of the steel MlO Unistrut connection method as a means of
fastening distinct PFRP shapes in a building system is characterised. Individ-
ual connector design parameters for joint stiffness and resistance are identified
and determined, under pure shear loading. The results of a series of physical
tests show no significant loss of stiffness or strength with long term environmen-
tal exposure. Values of key mechanical properties for design calculations are
recommended.
A 400 x 200 x 2848 mm prototype PFRP box beam assembly is fabricated from
two flange and two web panel-type shapes, cut from existing off-the-shelf PFRP
shapes. This is 60 mm deeper than the largest single PFRP shape that could
be used as a beam. The assembly is joined at the web-flange junction with M10
Unistrut connectors set at various spacing's, in the range 50 to 400 mm. These
connectors carry the longitudinal shear that is generated between the joined
shapes when the modular assembly is in flexure, Theoretical deflections, cal-
culated using a modified form of a partial-interaction analysis model developed
for composite concrete and steel structures, are predicted for the assembly ac-
counting for the finite shear stiffness of the web-flange connection. A series of
16 four-point bending load tests on the beam assembly, across two load arrange-
ments, show that its performance is linked to the designated spacing of the M10
Unistrut connections. The flexural rigidity and degree of interaction present in
the assembly are determined from analysis of vertical deflections and longitudi-
nal strains, as the beam is deformed. The influence of secondary effects, due to
the poor tolerances achieved in the hand fabrication of the beam's assembly, are
found to greatly affect the ability of the deflection analysis to give the required
measured deflections. Comparison of the effective joint shear rigidities obtained
from theory and testing indicates a higher individual connection stiffness in the
prototype beam than previously determined by way of the individual Unistrut
connector characterisation.
It is found through the combined analytical and physical testing research that
the M10 Unistrut connection method can only provide the necessary joint shear
stiffness and resistance to the 400 mm deep beam if the connector spacing, along
the four joints, is ≤ 50 mm. The total number of connectors this represents in the
beam is likely to make this modular construction approach too expensive for it to
be commercially viable. Although the M10 connector could be used to fabricate
beams of lesser depths, since the number of connectors will then be reduced, these
beams would find it difficult to compete with the available off-the-shelf PFRP
beam shapes, of up to 300 mm deep. There is however scope to use the Unistrut
method of connection to provide longitudinal shear resistance in building systems
where, for example, a floor panel is to be stiffened by a channel shaped beam and
the overall depth is ≤ 300 mm.
The research work contained in this thesis has contributed to a radical change
in the PFRP product offerings now proposed in the 2006 generation Startlink
building system
Risk of all-cause mortality associated with nonfatal AIDS and serious non-AIDS events among adults infected with HIV
No full textOpportunistic disease and mortality in patients coinfected with hepatitis B or C virus in the Strategic Management of Antiretroviral Therapy (SMART) study
No full textUdgivelsesdato: 2008-Dec-1BACKGROUND: In the Strategic Management of Antiretroviral Therapy (SMART) study, the risk of opportunistic disease (OD) and/or death due to any cause was elevated in the drug conservation (i.e., interrupt antiretroviral therapy until the CD4(+) cell count is <250 cells/microL) group, compared with the viral suppression (continued use of antiretroviral therapy) group. We assessed whether participants with concurrent hepatitis had an increased risk of the end points evaluated in the SMART study. METHODS: Participants were classified as being positive for hepatitis B virus (HBV) if they had positive hepatitis B surface antigen results for >6 months and positive for HCV if they tested HCV antibody positive. The rate and hazard ratio (HR) of OD and/or death and its 2 components were compared by hepatitis status and drug conservation versus the viral suppression group. RESULTS: Among 5472 participants enrolled from 8 January 2002 through 11 January 2006, 930 (17%) were HBV positive and/or HCV positive. The relative risk of non-OD death in participants randomized to the drug conservation group versus the viral suppression group was comparable regardless of hepatitis status (HR for coinfected and HIV-monoinfected participants, respectively, 1.9 [95% confidence interval {CI}, 1.0-3.9 and 1.8 [95% CI, 0.9-3.4]). The rate of OD or death was 3.9 events per 100 person-years in the coinfected group and 2.0 per 100 person-years in the HIV-monoinfected group. This excess risk was due to a higher risk of non-OD death among the coinfected participants (HR, 3.6; 95% CI, 2.3-5.6), whereas the risk of OD was comparable (HR, 1.1; 95% CI, 0.7-1.8). The 3 leading causes of non-OD death in coinfected participants were unknown cause, substance abuse, and non-acquired immunodeficiency disease cancer. CONCLUSIONS: Interruption of antiretroviral therapy is particularly unsafe in persons with hepatitis virus coinfection. Although HCV- and/or HBV-coinfected participants constituted 17% of participants in the SMART study, almost one-half of all non-OD deaths occurred in this population. Viral hepatitis was an unlikely cause of this excess risk
Short Communication: CD4 T Cell Declines Occurring During Suppressive Antiretroviral Therapy Reflect Continued Production of Casp8p41
No full textMost patients on suppressive antiretroviral therapy (ART) experience improvements in CD4 T cell count. However, some patients with undetectable viral load continue to lose CD4 T cells for unknown reasons. Casp8p41 is a host-derived protein fragment that is present only in productively infected cells and that causes the death of HIV-infected cells. We questioned whether ongoing CD4(+) T cell losses while on suppressive ART were associated with subclinical HIV replication causing production of Casp8p41. We analyzed the association of Casp8p41 content with subsequent CD4 losses in patients on continuous suppressive ART and in patients who discontinued ART after Casp8p41 content was determined, adjusting for age, baseline CD4(+) T cell count, and baseline HIV RNA level. Casp8p41 expression in memory CD4(+) T cells was measured by intracellular flow cytometry and was correlated with viral load and CD4(+) T cell change over time. In patients who stopped therapy after Casp8p41 content was determined, baseline Casp8p41 content did not predict CD4(+) T cell change. However, in patients on continuous ART, higher baseline Casp8p41 content was associated with a greater odds of a CD4(+) T cell decline at 6 months (p=0.01). Therefore, patients on suppressive ART, who have ongoing production of Casp8p41, have an increased risk of CD4 T cell losses, suggesting that subclinical HIV replication is driving both Casp8p41, which in turn causes a CD4(+) T cell decline
Lipoprotein particle subclasses, cardiovascular disease and HIV infection
No full textUdgivelsesdato: 2009-DecOBJECTIVE: To study the association of lipoprotein particles with CVD in a subgroup of HIV-infected patients who were enrolled in the Strategies for Management of Anti-Retroviral Therapy (SMART) study. SMART was a trial of intermittent use of ART (drug conservation [DC]) versus continuous of ART (viral suppression [VS]). METHODS: In a nested case-control study, lipoprotein particles (p) by nuclear magnetic resonance were measured at baseline and at the visit prior to the CVD event (latest levels) for 248 patients who had a CVD event and for 480 matched controls. Odds ratios (ORs) were estimated using conditional logistic models. RESULTS: Total, large and small HDL-p, but not VLDL-p nor LDL-p, were significantly and inversely associated with CVD and its major component, non-fatal coronary heart disease. The HDL-p associations with CVD were reduced after adjustment for high sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6) and D-dimer. Latest levels of total HDL-p were also significantly inversely associated with CVD; treatment interruption led to decrease of total HDL-p; adjusting for latest HDL-p did not explain the greater risk of CVD that was observed in the DC versus VS group. CONCLUSIONS: Lipoprotein particles, especially lower levels of small and large HDL-p identify HIV-infected patients at increased risk of CVD independent of other CVD risk factors
