Biomedical subjects

G Touloumi

Publications and source records attributed to G Touloumi.

At least 19 recordsLinked to original sources

PubMed2006

Seasonal confounding in air pollution and health time-series studies: effect on air pollution effect estimates.

A major statistical challenge in air pollution and health time-series studies is to adequately control for confounding effects of time-varying covariates. Daily health outcome counts are most commonly analysed by Poisson regression models, adjusted for overdispersion, with air pollution levels included as a linear predictor and smooth functions for calendar time and weather variables to adjust for time-varying confounders. Various smoothers have been used so far, but the optimal strategy for choosing smoothers and their degree of smoothing remains controversial. In this work, we evaluate the performance of various smoothers with different criteria for choosing the degree of smoothing in terms of bias and efficiency of the air pollution effect estimate in a simulation study. The evaluated approaches were also applied to real mortality data from 22 European cities. The simulation study imitated a multi-city study. Data were generated from a fully parametric model. Model selection methods which optimize prediction may lead to increased biases in the air pollution effect estimate. Minimization of the absolute value of the sum of the partial autocorrelation function of the model's residuals (PACF), as a criterion to choose the degree of smoothness, gave the smallest biases. The penalized splines (PS) method with a large number of effective dfs (e.g. 8-12 per year) could be used as the basic, relatively conservative, analysis whereas the PS and natural splines in combination with PACF could be applied to provide a reasonable range of the effect estimate.

Air Pollution↗

PubMed2006

Lamivudine monotherapy in HBeAg-negative chronic hepatitis B: prediction of response-breakthrough and long-term clinical outcome.

BACKGROUND: Factors that predict response and breakthrough phenomenon to lamivudine monotherapy in patients with HBeAg-negative chronic hepatitis B have not been well defined. AIM: To determine pre-treatment and on treatment variables that predict initial response and breakthrough in patients with HBeAg-negative chronic hepatitis B receiving long-term lamivudine. METHODS: Seventy-nine patients, with chronic HBeAg-negative hepatitis B, who received lamivudine for a median of 31 months were included in the study. RESULTS: Initial virologic and biochemical response was observed in 73 (92%) and 70 (89%) patients, respectively, while 34 (47%) and 15 (21%) patients developed virological and biochemical breakthrough, respectively. High levels of necroinflammation in liver biopsy were associated with a higher probability of initial virological and biochemical response. Patients with pre-treatment serum hepatitis B virus DNA concentrations of more than 10(6) copies/mL were three times more likely to develop virologic breakthrough. Two patients died, one with baseline cirrhosis because of liver failure during biochemical breakthrough while the second death was liver and treatment unrelated. CONCLUSIONS: In HBeAg-negative chronic hepatitis B, initial response to lamivudine therapy is associated with necroinflammation, while baseline serum hepatitis B virus DNA exceeding 10(6) copies/mL is a strong predictor for breakthrough because of drug-resistant mutations. Severe complications are uncommon and are associated with biochemical breakthrough and pre-existing cirrhosis.

Adolescent↗

PubMed2006

Short-term effects of nitrogen dioxide on mortality: an analysis within the APHEA project.

The short-term effects of nitrogen dioxide (NO(2)) on total, cardiovascular and respiratory mortality in 30 European cities participating in the Air Pollution on Health: a European Approach (APHEA)-2 project were investigated. The association was examined using hierarchical models implemented in two stages. In the first stage, data from each city were analysed separately, whereas in the second stage, the city-specific air pollution estimates were regressed on city-specific covariates to obtain overall estimates and to explore sources of possible heterogeneity. A significant association of NO(2) with total, cardiovascular and respiratory mortality was found, with stronger effects on cause-specific mortality. There was evidence of confounding in respiratory mortality with black smoke and sulphur dioxide. The effect of NO(2) on total and cardiovascular mortality was observed mainly in western and southern European cities, and was larger when smoking prevalence was lower and household gas consumption was higher. The effect of NO(2) on respiratory mortality was higher in cities with a larger proportion of elderly persons in the population and higher levels of particulate matter with a 50% cut-off aerodynamic diameter of 10 mum. The results of this large study are consistent with an independent effect of nitrogen dioxide on mortality, but the role of nitrogen dioxide as a surrogate of other unmeasured pollutants cannot be completely ruled out.

Air Pollutants↗

PubMed2005

Progression of HIV infection in the post-HAART era among a cohort of HIV+ Greek haemophilia patients.

AIM: The study aims to describe the course of HIV-1 infection in the pre- and post-HAART period in a cohort of HIV+ haemophilia patients followed up for up to 21 years. METHODS: The cohort includes 158 haemophilic men with known seroconversion dates followed up prospectively for a median time of 12 and 5.7 years in the pre- (1980-96) and post-HAART period (1997-2003), respectively. RESULTS: The risk of developing AIDS was lowered by 56% in the post- as compared to the pre-HAART period. Of the 158 patients 69 developed AIDS in the pre-HAART period while of the 59 subjects still alive and AIDS free on 1/1/1997 six developed AIDS. The rate of PCP (12.0 cases per 1000 person-years) and NHL (5.4 cases per 1000 person-years), the most common causes of AIDS diagnosis in the pre-HAART era, were remarkably reduced in the post-HAART era (both rates: 2.8 cases per 1000 person-years). On the contrary, the corresponding risk for non-AIDS deaths was fourfold increased in the post-HAART period. Of the 38 non-AIDS related deaths in both periods, 13 occurred post-HAART. The predominant cause of non-AIDS mortality in both periods was end-stage liver disease (ESLD) (7 pre- and 4 post-HAART). The rate of non-AIDS related cancers was also increased during the post-HAART period. CONCLUSION: In this haemophilia cohort the risk of AIDS has substantially reduced in the post-HAART period, but the rate of non-AIDS mortality tended to increase. Among haemophilia subjects, due to the high rates of HCV/HIV coinfection, ESLD, the predominant cause of non-AIDS mortality, will become an increasingly important clinical problem.

Acquired Immunodeficiency Syndrome↗

PubMed2005

Future trends of HCV-related cirrhosis and hepatocellular carcinoma under the currently available treatments.

SUMMARY: The epidemic of hepatitis C virus (HCV) infection is a major public health issue. We conducted a comprehensive analysis to estimate future HCV-related morbidity and mortality, using a model which is the first to take into account currently available treatments. We reconstructed the incident infections per year in the past that progressed to chronic hepatitis C (CHC) in Greece. Then, the natural history of the disease was simulated in subcohorts of newly infected subjects in the presence or absence of treatment using yearly estimates of the number of treated patients obtained from national databases. Annual estimates of the incidence and prevalence of CHC by fibrosis stage, hepatocellular carcinoma (HCC) and mortality were obtained up to 2030. The current proportion of naïve CHC patients receiving treatment in Greece is 1.2% per year. Treatment of 1.2-10% of naïve CHC patients per year would reduce the cumulative number of incident cirrhosis and HCC cases from 2002 to 2030 by 10.8-39.4% and 12.8-39.8%, respectively and decrease the number of prevalent cirrhosis and HCC cases in 2030 by approximately 17-48% compared with the number estimated under the assumption of no treatment. Approximately 17 cirrhosis cases or six HCC cases or 10 premature deaths would be prevented for every 100 treated patients. However, the prevalent cirrhotic/HCC cases because of HCV and HCV-related deaths would not plateau until 2030. Despite the introduction of effective treatment, HCV-related morbidity and mortality will likely increase during the next 20-30 years in Greece. Intensive primary prevention efforts coupled with increased access to the currently available treatments are necessary to control the chronic consequences of HCV epidemic.

Carcinoma, Hepatocellular↗

PubMed2004

Reconstructing and predicting the hepatitis C virus epidemic in Greece: increasing trends of cirrhosis and hepatocellular carcinoma despite the decline in incidence of HCV infection.

In this study, a comprehensive methodology for modelling the hepatitis C virus (HCV) epidemic is proposed to predict the future disease burden and assess whether the recent decline in the incidence of HCV may affect the future occurrence of cirrhosis and hepatocellular carcinoma (HCC) cases. Using the prevalence of HCV, the distribution of chronic hepatitis C (CHC) patients within the various transmission groups and their infection-onset times, it was possible to reconstruct the incident infections per year in the past that progressed to CHC in Greece. The natural history of the disease was simulated in subcohorts of newly infected subjects using transition probabilities derived either empirically between fibrosis stages 0-4 or from literature review. Annual estimates of the incidence and prevalence of CHC by fibrosis stage, HCC and mortality in Greece were obtained up to 2030. HCV incidence peaked in the late 1980s at five new infections/10,000 person-years. Under the assumption of 20-100% decline in HCV incidence after 1990, the cumulative number of incident cirrhosis and HCC cases from 2002-2030 was projected to be lower by 9.6-48.2% and 5.9-29.5%, respectively, than that estimated under the assumption of no decline. However, the prevalent cirrhotic/HCC cases and HCV-related deaths are predicted to decline in the next 30 years only under the assumption of complete elimination of new HCV infections after 1990. Despite the progress in the reduction of HCV transmission, primary prevention does not seem adequate to reverse the rise in the incidence of cirrhosis and HCC.

Carcinoma, Hepatocellular↗

PubMed2003

A comparison of two methods for the estimation of precision with incomplete longitudinal data, jointly modelled with a time-to-event outcome.

Several methods for the estimation and comparison of rates of change in longitudinal studies with staggered entry and informative drop-outs have been recently proposed. For multivariate normal linear models, REML estimation is used. There are various approaches to maximizing the corresponding log-likelihood; in this paper we use a restricted iterative generalized least squares method (RIGLS) combined with a nested EM algorithm. An important statistical problem in such approaches is the estimation of the standard errors adjusted for the missing data (observed data information matrix). Louis has provided a general technique for computing the observed data information in terms of completed data quantities within the EM framework. The multiple imputation (MI) method for obtaining variances can be regarded as an alternative to this. The aim of this paper is to develop, apply and compare the Louis and a modified MI method in the setting of longitudinal studies where the source of missing data is either death or disease progression (informative) or end of the study (assumed non-informative). Longitudinal data are simultaneously modelled with the missingness process. The methods are illustrated by modelling CD4 count data from an HIV-1 clinical trial and evaluated through simulation studies. Both methods, Louis and MI, are used with Monte Carlo simulations of the missing data using the appropriate conditional distributions, the former with 100 simulations, the latter with 5 and 10. It is seen that naive SEs based on the completed data likelihood can be seriously biased. This bias was largely corrected by Louis and modified MI methods, which gave broadly similar estimates. Given the relative simplicity of the modified MI method, it may be preferable.

Algorithms↗

PubMed2003

Investigating the dose-response relation between air pollution and total mortality in the APHEA-2 multicity project.

BACKGROUND: Several recent studies have reported significant health effects of air pollution even at low levels of air pollutants, but in most of these studies linear non-threshold relations were assumed. AIMS: To investigate the NO2 mortality dose-response association in nine cities participating in the APHEA-2 project using two different methods: the meta-smooth and the cubic spline method. METHODS: The meta-smooth method developed by Schwartz and Zanobetti is based on combining individual city non-parametric smooth curves; the cubic spline method developed within the APHEA-2 project combines individual city estimates of cubic spline shaped dose-response relations. The meta-smooth method is easier and faster to implement, but the cubic spline method is more flexible for further investigation of possible heterogeneity in the dose-response curves among cities. RESULTS: In the range of the pollutant common to all cities the two methods gave similar and comparable curves. Using the cubic spline method it was found that smoking prevalence acts as an effect modifier with larger NO2 effects on mortality at lower smoking prevalence. CONCLUSIONS: The NO2-mortality association in the cities included in the present analysis, could be adequately estimated using the linear model. However, investigation of the city specific dose-response curves should precede the application of linear models.

Air Pollutants↗

PubMed2003

Short-term effects of ambient particles on mortality in the elderly: results from 28 cities in the APHEA2 project.

Within the framework of the APHEA2 (Air Pollution on Health: a European Approach) project, the effects of ambient particles on mortality among persons > or = 65 yrs were investigated. Daily measurements for particles with a 50% cut-off aerodynamic diameter of 10 microm (PM10) and black smoke (BS), as well as the daily number of deaths among persons > or = 65 yrs of age, from 29 European cities, have been collected. Data on other pollutants and meteorological variables, to adjust for confounding effects and data on city characteristics, to investigate potential effect modification, were also recorded. For individual city analysis, generalised additive models extending Poisson regression, using a locally weighted regression (LOESS) smoother to control for seasonal effects, were applied. To combine individual city results and explore effect modification, second stage regression models were applied. The per cent increase (95% confidence intervals), associated with a 10 microg x m(-3) increase in PM10, in the elderly daily number of deaths was 0.8%, (0.7-0.9%) and the corresponding number for BS was 0.6%, (0.5-0.8%). The effect size was modified by the long-term average levels of nitrogen dioxide (higher levels were associated with larger effects), temperature (larger effects were observed in warmer countries), and by the proportion of the elderly in each city (a larger proportion was associated with higher effects). These results indicate that ambient particles have effects on mortality among the elderly, with relative risks comparable or slightly higher than those observed for total mortality and similar effect modification patterns. The effects among the older persons are of particular importance, since the attributable number of events will be much larger, compared to the number of deaths among the younger population.

Aged↗

PubMed2002

Significance of immune status, genotype and viral load in the severity of chronic hepatitis C in HIV infected haemophilia patients.

Chronic hepatitis C is associated with more severe liver disease in patients coinfected with HIV, but the pathogenic mechanism of this more aggressive course is still unclear. The aim of this study was to assess the relationship of HCV genotype, viral load and epidemiological factors with the histological severity of chronic hepatitis in haemophilia patients with HCV/HIV coinfection, taking into consideration the immune status of the patients. Twenty-one HIV/HCV coinfected haemophilia patients, with mean age +/- SD 35.7 +/- 8.7 years, underwent transcutaneous liver biopsy 6-15 years (median 12 years) after HIV and 6-32 (median 21.5 years) years after HCV infection. Twelve patients were stage A (CDC), six stage B and three stage C. CD4 cells were < 50 microL(-1) in three patients (14.3%), 50-200 in 11(52.4%) and > 200 in 7(33.3%). Mean +/- SD log(10) HCV-RNA was 6.87 +/- 0.7 copies mL(-1) (range 5.4-7.9), and mean +/- SD log(10) HIV-RNA was 3.75 +/- 0.98 copies mL(-1) (range 2.7-6), at the time of liver biopsy. Minimal hepatitis was diagnosed in five patients (24%), mild in 10 (48%) and moderate in six (28%). Hepatitis stage 0-2 was found in seven cases (33%) and cirrhosis in six (29%). Statistical analysis showed a significant association of CD4 count < 50 with minimal hepatitis and of CD > 200 with mild and moderate hepatitis (P = 0.033). In addition, minimal hepatitis was found only in patients with stage C, while the majority of subjects with HIV stage A showed mild and moderate hepatitis (P = 0.003). Moreover genotype 1 was independently associated with advanced hepatitis stage (P = 0.04). No relationship was found between hepatitis severity, HIV or HCV RNA levels, patient's age and duration of HIV or HCV infection. Our results suggest that HCV/HIV coinfection may aggravate the course of hepatitis in the phase of immunocompetence, most probably through an immune mediated process. Genotype 1 seems to be associated with advanced liver disease.

Adult↗

PubMed2001

Comparison of smoothing techniques for CD4 data in a Markov model with states defined by CD4: an example on the estimation of the HIV incubation time distribution.

Multi-state models defined in terms of CD4 counts are useful for modelling HIV disease progression. A Markov model with six progressive CD4-based states and an absorbing state (AIDS) was used to estimate the cumulative probability of progressing to AIDS in 158 HIV-1 infected haemophiliacs with known seroconversion (SC) dates. A problem arising in such analysis is how to define CD4-based states, since this marker is subject to measurement error and short timescale variability. Four approaches were used: no smoothing, ad hoc smoothing (to move to a later/previous state two consecutive measurements to later/previous states are needed), kernel smoothing and random effects (RE) models. The estimates were compared with the Kaplan-Meier estimate based solely on data concerning time to AIDS. There was an apparent lack of agreement between the Kaplan-Meier and the "no smoothing" estimate. With the exception of the "no smoothing" method, "ad hoc", kernel and RE estimates fell within the range of the 95 per cent CIs of the Kaplan-Meier curve. Simulations demonstrated that the use of raw CD4 counts provides overestimated transition intensities. Compared to the kernel method, ad hoc is easier to implement and overcomes the problem of the choice of bandwidth. The RE approach leads to simple models, since it usually results in very few transitions to previous states, and can handle individuals with sparse data by smoothing their predictions towards the population mean. Ad hoc was the method that performed better, in terms of bias, than the other smoothing approaches.

CD4 Lymphocyte Count↗

PubMed2001

Impact of missing data due to drop-outs on estimators for rates of change in longitudinal studies: a simulation study.

Many cohort studies and clinical trials are designed to compare rates of change over time in one or more disease markers in several groups. One major problem in such longitudinal studies is missing data due to patient drop-out. The bias and efficiency of six different methods to estimate rates of changes in longitudinal studies with incomplete observations were compared: generalized estimating equation estimates (GEE) proposed by Liang and Zeger (1986); unweighted average of ordinary least squares (OLSE) of individual rates of change (UWLS); weighted average of OLSE (WLS); conditional linear model estimates (CLE), a covariate type estimates proposed by Wu and Bailey (1989); random effect (RE), and joint multivariate RE (JMRE) estimates. The latter method combines a linear RE model for the underlying pattern of the marker with a log-normal survival model for informative drop-out process. The performance of these methods in the presence of missing data completely at random (MCAR), at random (MAR) and non-ignorable (NIM) were compared in simulation studies. Data for the disease marker were generated under the linear random effects model with parameter values derived from realistic examples in HIV infection. Rates of drop-out, assumed to increase over time, were allowed to be independent of marker values or to depend either only on previous marker values or on both previous and current marker values. Under MACR all six methods yielded unbiased estimates of both group mean rates and between-group difference. However, the cross-sectional view of the data in the GEE method resulted in seriously biased estimates under MAR and NIM drop-out process. The bias in the estimates ranged from 30 per cent to 50 per cent. The degree of bias in the GEE estimates increases with the severity of non-randomness and with the proportion of MAR data. Under MCAR and MAR all the other five methods performed relatively well. RE and JMRE estimates were more efficient(that is, had smaller variance) than UWLS, WLS and CL estimates. Under NIM, WLS and particularly RE estimates tended to underestimate the average rate of marker change (bias approximately 10 per cent). Under NIM, UWLS, CL and JMRE performed better in terms of bias (3-5 per cent) with the JMRE giving the most efficient estimates. Given that markers are key variables related to disease progression, missing marker data are likely to be at least MAR. Thus, the GEE method may not be appropriate for analysing such longitudinal marker data. The potential biases due to incomplete data require greater recognition in reports of longitudinal studies. Sensitivity analyses to assess the effect of drop-outs on inferences about the target parameters are important.

Adolescent↗

PubMed2001

Acute effects of particulate air pollution on respiratory admissions: results from APHEA 2 project. Air Pollution and Health: a European Approach.

The APHEA 2 project investigated short-term health effects of particles in eight European cities. In each city associations between particles with an aerodynamic diameter of less than 10 microm (PM(10)) and black smoke and daily counts of emergency hospital admissions for asthma (0-14 and 15-64 yr), chronic obstructive pulmonary disease (COPD), and all-respiratory disease (65+ yr) controlling for environmental factors and temporal patterns were investigated. Summary PM(10) effect estimates (percentage change in mean number of daily admissions per 10 microg/m(3) increase) were asthma (0-14 yr) 1.2% (95% CI: 0.2, 2.3), asthma (15-64 yr) 1.1% (0.3, 1.8), and COPD plus asthma and all-respiratory (65+ yr) 1.0% (0.4, 1.5) and 0.9% (0.6, 1.3). The combined estimates for Black Smoke tended to be smaller and less precisely estimated than for PM(10). Variability in the sizes of the PM(10) effect estimates between cities was also investigated. In the 65+ groups PM(10) estimates were positively associated with annual mean concentrations of ozone in the cities. For asthma admissions (0-14 yr) a number of city-specific factors, including smoking prevalence, explained some of their variability. This study confirms that particle concentrations in European cities are positively associated with increased numbers of admissions for respiratory diseases and that some of the variation in PM(10) effect estimates between cities can be explained by city characteristics.

Acute Disease↗

PubMed2001

Comparative evaluation of the QUANTIPLEX HIV-1 RNA 2.0 and 3.0 (bDNA) assays and the AMPLICOR HIV-1 MONITOR v1.5 test for the quantitation of human immunodeficiency virus type 1 RNA in plasma.

HIV-1 RNA measurements from 84 plasma specimens obtained with the QUANTIPLEX HIV-1 RNA 2.0 and 3.0 (bDNA) assays (Chiron Diagnostics, Emeryville, CA) and with the AMPLICOR HIV-1 MONITOR Test, version 1.5 with ultra-sensitive specimen preparation (Roche Diagnostic Systems, Inc., Branchburg, NJ) were compared. The absolute RNA values of tested specimens differed significantly between bDNA 2.0 and bDNA 3.0 or Monitor v1.5 measurements (Wilcoxon signed-rank test P<0.001). Results generated with bDNA 3.0 or with Monitor v1.5 were approximately twofold greater than those generated with bDNA 2.0, with smaller differences at higher HIV-1 RNA levels and greater differences at RNA levels below 1000 copies per ml. Although highly correlated (r=0.92 and 0.86, respectively), viral load data generated with bDNA 2.0 and either bDNA 3.0 or Monitor v1.5 were in poor agreement. Concordant results (difference in log(10) copies per ml <0.5) were found at frequencies of 80% for bDNA 2.0 and bDNA 3.0 and only at 58.5% for bDNA 2.0 and Monitor v1.5. In contrast, bDNA 3.0 and Monitor v1.5 measurements were highly correlated (r=0.96) and in good agreement (92.7%).

Adult↗

PubMed2001

Confounding and effect modification in the short-term effects of ambient particles on total mortality: results from 29 European cities within the APHEA2 project.

We present the results of the Air Pollution and Health: A European Approach 2 (APHEA2) project on short-term effects of ambient particles on mortality with emphasis on effect modification. We used daily measurements for particulate matter less than 10 microm in aerodynamic diameter (PM10) and/or black smoke from 29 European cities. We considered confounding from other pollutants as well as meteorologic and chronologic variables. We investigated several variables describing the cities' pollution, climate, population, and geography as potential effect modifiers. For the individual city analysis, generalized additive models extending Poisson regression, using a smoother to control for seasonal patterns, were applied. To provide quantitative summaries of the results and explain remaining heterogeneity, we applied second-stage regression models. The estimated increase in the daily number of deaths for all ages for a 10 microg/m3 increase in daily PM10 or black smoke concentrations was 0.6% [95% confidence interval (CI) = 0.4-0.8%], whereas for the elderly it was slightly higher. We found important effect modification for several of the variables studied. Thus, in a city with low average NO2, the estimated increase in daily mortality for an increase of 10 microg/m3 in PM10 was 0.19 (95% CI = 0.00-0.41), whereas in a city with high average NO2 it was 0.80% (95% CI = 0.67-0.93%); in a relatively cold climate the corresponding effect was 0.29% (95% CI = 0.16-0.42), whereas in a warm climate it was 0.82% (95% CI = 0.69-0.96); in a city with low standardized mortality rate it was 0.80% (95% CI = 0.65-0.95%), and in one with a high rate it was 0.43% (95% CI = 0.24-0.62). Our results confirm those previously reported on the effects of ambient particles on mortality. Furthermore, they show that the heterogeneity found in the effect parameters among cities reflects real effect modification, which is explained by specific city characteristics.

Aged↗

PubMed2001

Investigating regional differences in short-term effects of air pollution on daily mortality in the APHEA project: a sensitivity analysis for controlling long-term trends and seasonality.

Short-term effects of air pollution on daily mortality in eight western and five central-eastern European countries have been reported previously, as part of the APHEA project. One intriguing finding was that the effects were lower in central-eastern European cities. The analysis used sinusoidal terms for seasonal control and polynomial terms for meteorologic variables, but this is a more rigid approach than the currently accepted method, which uses generalized additive models (GAM). We therefore reanalyzed the original data to examine the sensitivity of the results to the statistical model. The data were identical to those used in the earlier analyses. The outcome was the daily total number of deaths, and the pollutants analyzed were black smoke (BS) and sulfur dioxide (SO(2)). The analyses were restricted to days with pollutant concentration < 200 microg/m(3) and < 150 microg/m(3) alternately. We used Poisson regression in a GAM model, and combined individual city regression coefficients using fixed and random-effect models. An increase in BS by 50 microg/m(3) was associated with a 2.2% and 3.1% increase in mortality when analysis was restricted to days < 200 microg/m(3) and < 150 microg/m(3), respectively. The corresponding figures were 5.0% and 5.6% for a similar increase in SO(2). These estimates are larger than the ones published previously: by 69% for BS and 55% for SO(2). The increase occurred only in central-eastern European cities. The ratio of western to central-eastern cities for estimates was reduced to 1.3 for BS (previously 4.8) and 2.6 for SO(2) (previously 4.4). We conclude that part of the heterogeneity in the estimates of air pollution effects between western and central-eastern cities reported in previous publications was caused by the statistical approach used and the inclusion of days with pollutant levels above 150 microg/m(3). However, these results must be investigated further.

Adolescent↗

PubMed2000

Predictors of clinical outcome and radiologic progression in patients with neuropsychiatric manifestations of systemic lupus erythematosus.

PURPOSE: We sought to identify the predictors of clinical outcome and of the evolution of cerebral abnormalities in patients with neuropsychiatric systemic lupus erythematosus (SLE). SUBJECTS AND METHODS: Thirty-two patients with SLE (including 14 with the antiphospholipid syndrome) who had been hospitalized with primary neuropsychiatric disease were observed prospectively for at least 2 years. Laboratory and clinical characteristics and data from magnetic resonance imaging (MRI) studies obtained during the hospitalization and 2 years later were evaluated. We ascertained nonreversible or new MRI changes and clinical outcomes, including neuropsychiatric events, during follow-up. RESULTS: Cranial MRI scans on admission were abnormal in 26 (81%) of the 32 patients. Patients with the antiphospholipid syndrome were more likely to have focal cerebral white matter lesions (odds ratio [OR] = 12, 95% confidence interval [CI]: 2.0 to 72). After 2 years, neuropsychiatric deficits substantially improved in 22 (69%) of the patients, stabilized in 6 (19%), and deteriorated in 4 (12%). The number of prior neuropsychiatric events was associated with persistent MRI lesions (OR = 4.8 per each event, 95% CI: 1.1 to 21) and unfavorable clinical outcome (OR = 4.3 per each event, 95% CI: 1.4 to 13) at 2 years. The antiphospholipid syndrome also predicted an unfavorable clinical outcome at 2 years (OR = 11, 95% CI: 1.7 to 65). CONCLUSIONS: Among patients with SLE who have neuropsychiatric disease, prior neuropsychiatric events and the antiphospholipid syndrome increase the risk of adverse outcomes.

Adult↗

PubMed2000

Effect of recent thymic emigrants on progression of HIV-1 disease.

BACKGROUND: The concentration of T-cell receptor-rearrangement excision DNA circles (TREC) in peripheral-blood T cells is a marker of recent thymic emigrant alphabeta T cells. We studied the predictive ability of measurements of TREC for clinical outcome in HIV-1-infected individuals. METHODS: We measured TREC in peripheral-blood mononuclear cells with a real-time PCR assay. We studied 131 Greek participants in the Multicenter Hemophilia Cohort Study who had known HIV-1 seroconversion dates. The prognostic value of baseline TREC, CD4 T-cell count, and HIV-1 RNA concentration was assessed by Kaplan-Meier and Cox's regression analysis. FINDINGS: Four participants had progressed to AIDS by first blood sampling. Among the remaining 127 individuals, the median value of TREC per 10(6) cells was 6900 (IQR 2370-15604). Baseline TREC values were lower in the 53 who progressed to AIDS than in those who did not (geometric mean 2843 [95% CI 1468-5504] vs 6560 [4723-9113] per 10(6) cells; p=0.017). The relative hazard of AIDS, adjusted for plasma viral load, CD4 T-cell count, and age at seroconversion was 1.44 (95% CI 1.04-2.01; p=0.031) per ten-fold increase in TREC; that for death was 1.52 (1.12-2.06; p=0.007). The adjusted relative hazards of death were 2.91 (1.91-4.44; p<0.001) per ten-fold increase in plasma HIV-1 RNA load and 1.20 (1.04-1.38; p=0.014) per 100-cell decrease in CD4 T-cell count. INTERPRETATION: The concentration of TREC in the peripheral T-cell pool complements HIV-1 RNA load and CD4 T-cell count in predicting the rate of HIV-1 disease progression. Recent thymic emigrants have a role in the pathogenesis of HIV-1 disease.

Adult↗