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Biomedical subjects

Giota Touloumi

Publications and source records attributed to Giota Touloumi.

7 recordsLinked to original sources
PubMed2003

Elevated serum levels of soluble immune activation markers are associated with increased risk for death in HAART-naive HIV-1-infected patients.

The aim of this study was to determine the serum levels of soluble markers reflecting different aspects of immune activation in HIV-1-infected patients, and assess their prognostic significance for occurrence of AIDS-related death before the advent of the highly active antiretroviral treatment (HAART). Serum concentrations of the soluble forms of interleukin-2 receptors (sIL-2R), intercellular adhesion molecule-1 (sICAM-1), and E-selectin (sEs) have been determined in a cohort of 64 HIV-1-infected patients, between 1990-1993. The patients were followed prospectively with regular visits at the outpatient department. Follow-up time was censored at January 1, 1997, the date after which HAART was introduced. The median follow-up time was 46 months (range, 2-78 months). By the end of follow-up, 34 subjects had died. Baseline levels of all three soluble markers were significantly lower in subjects who remained alive during the follow-up compared to subjects who died. Univariate analysis showed that individual sIL-2R and sICAM-1, but not sEs measurements, were significantly associated with time to death (p = 0.008 and 0.003, respectively). Even after adjustment for age and CD4+ T-cell counts sIL-2R measurements remained significantly prognostic. Sensitivity analysis using follow-up time to year 2000 confirmed these results. Our data suggest that assessment of the immune activation status using the easily measured levels of circulating markers may provide additional information about the risk of AIDS-related death. Further studies are needed to assess the effect of HAART on the levels of immune activation markers and their prognostic value.

Adult↗
PubMed2003

The temporal pattern of respiratory and heart disease mortality in response to air pollution.

Short-term changes in ambient particulate matter with aerodynamic diameters < 10 micro m (PM10) have been associated with short-term fluctuations in mortality or morbidity in many studies. In this study, we tested whether those deaths are just advanced by a few days or weeks using a multicity hierarchical modeling approach for all-cause, respiratory, and cardiovascular deaths, for all ages and stratifying by age groups, within the APHEA-2 (Air Pollution and Health: A European Approach) project. We fit a Poisson regression and used an unconstrained distributed lag to model the effect of PM10 exposure on deaths up to 40 days after the exposure. In baseline models using PM10 the day of and day before the death, we found that the overall PM10 effect (per 10 micro g/m3) was 0.74% [95% confidence interval (95% CI), -0.17 to 1.66] for respiratory deaths and 0.69% (95% CI, 0.31-1.08) for cardiovascular deaths. In unrestricted distributed lag models, the effect estimates increased to 4.2% (95% CI, 1.08-7.42) for respiratory deaths and to 1.97% (95% CI, 1.38-2.55) for cardiovascular deaths. Our study confirms that most of the effect of air pollution is not simply advanced by a few weeks and that effects persist for more than a month after exposure. The effect size estimate for PM10 doubles when we considered longer-term effects for all deaths and for cardiovascular deaths and becomes five times higher for respiratory deaths. We found similar effects when stratifying by age groups. These larger effects are important for risk assessment.

Adolescent↗
PubMed2002

Changes over calendar time in the risk of specific first AIDS-defining events following HIV seroconversion, adjusting for competing risks.

BACKGROUND: Although studies have reported large reductions in the risks of AIDS and death since the introduction of potent anti-retroviral therapies, few have evaluated whether this has been similar for all AIDS-defining diseases. We wished to evaluate changes over time in the risk of specific AIDS-defining diseases, as first events, using data from individuals with known dates of HIV seroconversion. METHODS: Using a competing risks proportional hazards model on pooled data from 20 cohorts (CASCADE), we evaluated time from HIV seroconversion to each first AIDS-defining disease (16 groups) and to death without AIDS for four calendar periods, adjusting for exposure category, age, sex, acute infection, and stratifying by cohort. We compared results to those obtained from a cause-specific hazards model. RESULTS: Of 6,941, 2,021 (29%) developed AIDS and 437 (6%) died without AIDS. The risk of AIDS or death remained constant to 1996 then reduced; relative hazard = 0.89 (95% CI: 0.77-1.03); 0.90 (95% CI: 0.81-1.01); and 0.32 (95% CI: 0.28-0.37) for 1979-1990, 1991-1993, and 1997-2001, respectively, compared to 1994-1996. Significant risk reductions in 1997-2001 were observed in all but two AIDS-defining groups and death without AIDS in a competing risks model (with similar results from a cause-specific model). There was significant heterogeneity in the risk reduction across events; from 96% for cryptosporidiosis, to 17% for death without AIDS (P < 0.0001). CONCLUSION: These findings suggest that studies reporting a stable trend for particular AIDS diseases over the period 1979-2001 may not have accounted for the competing risks among other events or lack the power to detect smaller trends.

AIDS-Related Opportunistic Infections↗
PubMed2002

The temporal pattern of mortality responses to air pollution: a multicity assessment of mortality displacement.

Although the association between particulate matter and mortality or morbidity is generally accepted, controversy remains about the importance of the association. If it is due solely to the deaths of frail individuals, which are brought forward by only a brief period of time, the public health implications of the association are fewer than if there is an increase in the number of deaths. Recently, other research has addressed the mortality displacement issue in single-city analysis. We analyzed this issue with a distributed lag model in a multicity hierarchic modeling approach, within the Air Pollution and Health: A European Approach (APHEA-2) study. We fit a Poisson regression model and a polynomial distributed lag model with up to 40 days of delay in each city. In the second stage we combined the city-specific results. We found that the overall effect of particulate matter less than 10 microM in aerodynamic diameter (PM10) per 10 microg/m3 for the fourth-degree distributed lag model is a 1.61% increase in daily deaths (95% CI = 1.02-2.20), whereas the mean of PM10 on the same day and the previous day is associated with only a 0.70% increase in deaths (95% CI = 0.43-0.97). This result is unchanged using an unconstrained distributed lag model. Our study confirms that the effects observed in daily time-series studies are not due primarily to short-term mortality displacement. The effect size estimate for airborne particles more than doubles when we consider longer-term effects, which has important implications for risk assessment.

Air Pollutants↗
PubMed2002

Impact of missing data due to selective dropouts in cohort studies and clinical trials.

BACKGROUND: Many cohort studies and clinical trials use repeated measurements of laboratory markers to track disease progression and to evaluate new therapies. A major problem in the analysis of such studies is that marker data are censored in some patients owing to withdrawal, loss to follow-up, or death. The objective of this paper is to evaluate the impact of selective dropouts attributable to death or disease progression on the estimates of marker change among different groups. METHODS: Data on CD4 cell count in human immunodeficiency virus 1-infected individuals from a clinical trial and a cohort study are used to illustrate this problem and a possible solution. Simulation studies are also presented. RESULTS: When the rate of dropout is greater in subjects whose marker status is declining rapidly, commonly used methods, like random effects models, that ignore informative dropouts lead to overoptimistic statements about the marker trends in all compared groups, because subjects with steeper marker drops tend to have shorter follow-up times and hence are weighted less in the estimation of the group rate of the average marker decline. CONCLUSIONS: The potential biases attributable to incomplete data require greater recognition in longitudinal studies. Sensitivity analyses to assess the effect of dropouts are important.

Adolescent↗
PubMed2002

Quantitation of human immunodeficiency virus type 1 DNA forms with the second template switch in peripheral blood cells predicts disease progression independently of plasma RNA load.

There are several forms of human immunodeficiency virus type 1 (HIV-1) DNA in peripheral blood T cells and lymph nodes in untreated HIV-1-infected individuals and in patients whose plasma HIV-1 RNA levels are suppressed by long-term combination antiretroviral therapy. However, it remains to be established whether the concentration of HIV-1 DNA in cells predicts the clinical outcome of HIV-1 infection. In this report, we measured the concentration of HIV-1 DNA forms which has undergone the second template switch (STS DNA) and 2-long-terminal-repeat DNA circles in peripheral blood mononuclear cell (PBMC) samples. To do this, we used molecular-beacon-based real-time PCR assays and studied 130 patients with hemophilia in the Multicenter Hemophilia Cohort Study. We assessed the influence of baseline HIV-1 STS DNA levels on the progression of HIV-1 disease in the absence of combination antiretroviral therapy by Kaplan-Meier and Cox regression analysis. Among the patients who progressed to AIDS, the median levels (interquartile ranges) of STS HIV-1 DNA in PBMC were significantly higher than those of patients who remained AIDS free during the 16 years of follow-up (1,017 [235 to 6,059] and 286 [31 to 732] copies per 10(6) PBMC, respectively; P < 0.0001). Rates of progression to death and development of AIDS varied significantly (log rank P < 0.001) by quartile distribution of HIV-1 STS DNA levels. After adjustment for age at seroconversion, baseline CD4(+) T-cell counts, plasma viral load, and T-cell-receptor excision circles, the relative hazards (RH) of death and AIDS were significantly increased with higher HIV-1 STS DNA levels (adjusted RH, 1.84 [95% confidence interval (CI), 1.30 to 2.59] and 2.62 [95% CI, 1.75 to 3.93] per 10-fold increase per 10(6) PBMC, respectively). HIV-1 STS DNA levels in each individual remained steady in longitudinal PBMC samples during 16 years of follow-up. Our findings show that the concentration of HIV-1 STS DNA in PBMC complements the HIV-1 RNA load in plasma in predicting the clinical outcome of HIV-1 disease. This parameter may have important implications for understanding the virological response to combination antiretroviral therapy.

DNA, Viral↗