Search PubMed⌕ Search

Biomedical subjects

H Jacqmin-Gadda

Publications and source records attributed to H Jacqmin-Gadda.

At least 19 recordsLinked to original sources
PubMed2006

Determinants of response to first HAART regimen in antiretroviral-naïve patients with an estimated time since HIV seroconversion.

OBJECTIVE: To study the determinants of immunological and virological response to highly active antiretroviral therapy (HAART) in naïve patients, adjusting for time since HIV-1 seroconversion. DESIGN: Data from HIV-cohort studies where dates of seroconversion have been reliably estimated. Methods In previously untreated patients, short- and long-term marker responses from HAART initiation (three or more antiretroviral drugs) to the end of follow-up or any treatment modification were considered using mixed effects models accounting for undetectable HIV viral load and informative dropout. RESULTS: In total, 943 patients were treated with a first HAART regimen for a median of 29 months. In adjusted analyses, compared with a reference group of homosexual men without AIDS initiating treatment 4 years after seroconversion, injecting drug users (IDUs) were treated at similar CD4 and HIV RNA levels but had poorer short-term virological response (2.54 vs 2.13 log(10) HIV-1 RNA copies/mL at 1.5 months, P=0.03) and poorer long-term immunological response (522 vs 631 cells/microL at 24 months, P<0.0001). Although individuals with AIDS at HAART initiation had lower CD4 counts (206 vs 382 cells/microL, P<0.0001), their immunological responses were similar to those of individuals without AIDS. Similarly, individuals further from seroconversion started HAART at lower CD4 counts (e.g. 311 vs 382 cells/microL at vs before 9 years from seroconversion, P<0.0001), but had similar CD4 responses. However, they experienced poorer long-term virological response (0.67 log(10) copies/mL/year smaller decline, P<0.0001) compared to those treated before 9 years from seroconversion. CONCLUSION: Taking into account the time elapsed since seroconversion, this study suggests that careful choices of initial treatment should be made and intensive follow-up carried out in high-risk subgroups such as IDUs who have poorer responses.

Adult↗
PubMed2004

[Joint modeling of quantitative longitudinal data and censored survival time].

BACKGROUND: In epidemiology, we are often interested in the association between the evolution of a quantitative variable and the onset of an event. The aim of this paper is to present a joint model for the analysis of Gaussian repeated data and survival time. Such models allow, for example, to perform survival analysis when a time-dependent explanatory variable is measured intermittently, or to study the evolution of a quantitative marker conditionally to an event. METHODS: They are constructed by combining a mixed model for repeated Gaussian variables and a survival model which can be parametric or semi-parametric (Cox model). RESULTS: We discuss the hypotheses underlying the different joint models proposed in the literature and the necessary assumptions for maximum likelihood estimation. The interest of these methods is illustrated with a study of the natural history of dementia in a cohort of elderly persons.

Biometry↗
PubMed2003

A latent process model for joint modeling of events and marker.

The paper formulates joint modeling of a counting process and a sequence of longitudinal measurements, governed by a common latent stochastic process. The latent process is modeled as a function of explanatory variables and a Brownian motion process. The conditional likelihood given values of the latent process at the measurement times, has been drawn using Brownian bridge properties; then integrating over all possible values of the latent process at the measurement times leads to the desired joint likelihood. An estimation procedure using joint likelihood and a numerical optimization is described. The method is applied to the study of cognitive decline and Alzheimer's disease.

Aged↗
PubMed2002

Longitudinal analysis of the effect of apolipoprotein E epsilon4 and education on cognitive performance in elderly subjects: the PAQUID study.

BACKGROUND: The apolipoprotein E (apoE) epsilon4 allele has been shown to be a risk factor for dementia, but it is not clear to what extent apoE affects overall cognitive function in non-demented elderly subjects, or how this risk may be modified by gene-environment interactions. OBJECTIVE: To examine changes in cognitive function in elderly people as a function of the apoE epsilon4 phenotype. METHODS: A community based prospective cohort study of 600 non-demented subjects aged over 65 years living in Gironde (France) was analysed to evaluate change over time (seven years) in scores on the mini-mental state examination (MMSE). RESULTS: Age at cohort inception was negatively associated with cognitive performance for both epsilon4 carriers and non-carriers (p < 0.001). The evolution of MMSE scores differed as a function of age: scores remained stable among younger subjects but decreased over time in older subjects. The epsilon4 allele was shown to be significantly associated with lower cognitive performance at baseline (p = 0.02). The course of cognitive performance during the follow up was the same for both epsilon4 carriers and non-carriers. Lower educational level was associated with lower cognitive performance at baseline (p < 0.001) and the effect of an epsilon4 allele on cognitive performance disappeared after adjustment for education. When incident cases of dementia were excluded, the results were unchanged except for the course of the MMSE scores, which now remained stable over time in the older subjects. CONCLUSIONS: apoE epsilon4 carriers show decreased MMSE scores compared with epsilon4 non-carriers, but the effect of apoE on cognition disappears after adjustment for education. Non-demented elderly people maintain a stable cognitive performance regardless of their apoE phenotype.

Aged↗
PubMed2001

Modeling changes in CD4-positive T-lymphocyte counts after the start of highly active antiretroviral therapy and the relation with risk of opportunistic infections: the Aquitaine Cohort, 1996-1997.

After initiation of a treatment for human immunodeficiency virus type 1 infection containing a protease inhibitor, immune restoration associated with increases in CD4-positive (CD4+) T lymphocyte count may be delayed. In a sample of patients who had been prescribed protease inhibitors for the first time, the authors tested to see whether there was a minimal duration of CD4+ cell count increase before the increase had an impact on the occurrence of opportunistic infections. The evolution (difference between time t and baseline) of CD4+ cell count was modeled using a mixed effects linear model. Changes in CD4+ count estimated by this model were then included as time-dependent covariates in a proportional hazards model. Finally, the authors tested for the existence of a CD4+ change x time interaction. The authors used a sample of 553 French patients first prescribed protease inhibitors in 1996 and followed for a median of 16 months. During the first 120 days, there was no association between CD4+ change and the rate of opportunistic infections. After 120 days, each 50-cell/mm3 increase in CD4+ count was associated with a 60% (95% confidence interval: 45, 72) reduction in the incidence of opportunistic infections. These results, based on modeling of CD4+ cell response, at least indirectly reinforce the concept of a delayed but possible immune recovery with the use of protease inhibitors. The findings support the potential for interruption of certain types of prophylaxis against opportunistic infections under reasonable conditions of duration of antiretroviral therapy and sustained CD4+ cell response.

AIDS-Related Opportunistic Infections↗
PubMed2001

Viral load as a primary outcome in human immunodeficiency virus trials: a review of statistical analysis methods.

In Human Immunodeficiency Virus infection, several statistical methods are available to analyze viral load (HIV-1 RNA) used as a surrogate outcome in trials of antiretroviral treatments. We compared the most frequently used methods and applied them to one of these trials, where HIV-1 RNA was measured using two lower limits of detection. Methods were reviewed for different properties dealing with validity, interpretation, and handling. Compared to change of HIV-1 RNA at the end of follow-up or HIV-1 RNA area-under-the-curve during follow-up minus baseline, the most attractive methods appeared to be HIV-1 RNA undetectability, HIV-1 RNA reduction at the end of follow-up with censoring adjustment, and mixed linear model on HIV-1 RNA.

Area Under Curve↗
PubMed2000

Relation between aluminum concentrations in drinking water and Alzheimer's disease: an 8-year follow-up study.

To investigate the effect of aluminum and silica in drinking water on the risk of dementia and Alzheimer's disease, the authors analyzed data from a large prospective cohort (Paquid), including 3,777 subjects aged 65 years and over living at home in 75 civil parishes in Gironde and Dordogne in southwestern France in 1988-1989. The subjects were followed for up for 8 years with an active search for incident cases of dementia or Alzheimer's disease. Mean exposure to aluminum and silica in drinking water was estimated in each area. The sample studied included 2,698 nondemented subjects at baseline, for whom components of drinking water and covariates were available. A total of 253 incident cases of dementia (with 17 exposed to high levels of aluminum), including 182 Alzheimer's disease (with 13 exposed to high aluminum levels), were identified. The relative risk of dementia adjusted for age, gender, educational level, place of residence, and wine consumption was 1.99 (95 percent CI: 1.20, 3.28) for subjects exposed to an aluminum concentration greater than 0.1 mg/liter. This result was confirmed for Alzheimer's disease (adjusted relative risk = 2.14, 95 percent CI: 1.21, 3.80). However, no dose-response relation was found. Inversely, the adjusted relative risk of dementia for subjects exposed to silica (> or = 11.25 mg/liter) was 0.74 (95 percent CI: 0.58, 0.96). These findings support the hypothesis that a high concentration of aluminum in drinking water may be a risk factor for Alzheimer's disease.

Aged↗
PubMed2000

Clinical progression of HIV-1 infection according to the viral response during the first year of antiretroviral treatment. Groupe d'Epidémiologie du SIDA en Aquitaine (GECSA).

OBJECTIVE: To compare HIV-disease progression according to changes of plasma HIV RNA observed in the year following initiation of a new antiretroviral treatment. DESIGN: Prospective cohort treated with two nucleoside analogues or a triple combination including a protease inhibitor. METHODS: A Cox model was used to estimate the effect of viral response during the first year after initiation of treatment on the subsequent occurrence of new AIDS-defining events or death. Viral response was fitted either as HIV RNA reduction during the initial 4-12 months of treatment or reduction during the first month. RESULTS: Among 773 patients (47% with triple drug combination) followed for a median period of 27 months, 62 patients experienced a clinical event. Poor viral responders (at least two measurements > 3.7 log10 copies/ml during 4-12 months of treatment) had a higher risk of disease progression than good responders (RNA < 2.7 log10 copies/ml) after adjustment [hazard ratio (HR), 2.24; 95% confidence interval (CI), 1.1 7-4.29]. Intermediate responders (2.7 < or = RNA < or = 3.7 log10 copies/ml) had a risk of progression comparable with that of good responders (HR, 1.43; 95% CI, 0.64-3.22). A large initial viral reduction was also a protective factor for clinical progression (HR, 0.51 for 1 log10 copies/ml increase of the reduction; 95% CI, 0.31-0.85) and was associated with the viral response during the subsequent 4-12 month period. No patient with a reduction < 0.5 log10 copies/ml in the first month was classified as a good responder in the subsequent 4-12 month period (P < 0.01). CONCLUSIONS: A sustained HIV RNA > 3.7 log10 copies/ml should suggest a prompt change of treatment. When the reduction in HIV RNA is < 0.5 log10 after 1 month of treatment, this action should be anticipated. A sustained HIV RNA level between 2.7 and 3.7 log10 copies/ml may permit the deferral of a change of drug regimen according to the patient's history and therapeutic options.

Adult↗
PubMed2000

Serum triglycerides, HIV infection, and highly active antiretroviral therapy, Aquitaine Cohort, France, 1996 to 1998. Groupe d'Epidémiologie Clinique du Sida en Aquitaine (GECSA).

The aim of this study was to identify factors associated with serum triglyceride (TG) evolution in HIV-1-infected patients when highly active antiretroviral treatment (HAART) with or without protease inhibitors (PI) was introduced. Among 3191 patients of the Aquitaine Cohort (multirisk, both genders, multiple treatment patterns) observed during 1996 through 1998, 1429 had at least two measurements of TG, viral load, and CD4 cell count. Median follow-up was 21 months (interquartile range [IQR], 11-26) and median number of TG measures was 6 (IQR, 3-10). Median TG at baseline was 1.32 mmol/L (IQR, 0.91-2.05) and increased significantly over time (+2.5% for 100 days; 95% confidence interval [CI], 1.9-3.1). Longitudinal analysis of variations of TG was performed using mixed models. In crude analysis, baseline TG was higher in men, in those aged over 36 years, and in homosexuals. The following time-dependent variables were associated with an increase of TG: body weight increasing to >65 kg, diagnosis of AIDS, CD4 cell count falling to <50 cells/mm3, viral load falling to <500 cp/ml, and introduction of nucleoside analogues and PIs. In multivariate analysis, age >36 years (change of +17% of the TG level; 95% CI, 11-24), homosexuals (+13%; 95% CI, 4-23), AIDS stage (+12%; 95% CI, 5-19), weight >65 kg (+7%; 95% CI, 2-12) and PI (+21%; 95% CI, 17-27) remained significant. Factors identified before the availability of PI remain important but HAART with PI is a new major contributing factor to increased TG levels.

Adult↗
PubMed2000

A cognitive screening battery for dementia in the elderly.

The objective of this study is to propose a screening instrument for dementia based on a reduced number of neuropsychological tests. The sample consists in the pooled data of the five follow-up visits of the Paquid cohort study on cerebral aging: the estimation sample included 2792 subjects (8830 observations) and the validation sample included 985 subjects (2643 observations). Among scores significantly associated with dementia, we retained only those that increased the specificity of the model for a sensitivity of one. Seven neuropsychological tests and the MMSE subscores were considered. The most discriminant combination of tests included the MMSE and the subscores "orientation to time" and "recall three objects," the Benton Visual Retention Test, and Isaacs' Set Test of verbal fluency. The specificity of this screening instrument was 0. 77 for a sensitivity of 1.

Activities of Daily Living↗
PubMed2000

Intake of flavonoids and risk of dementia.

It has been postulated that oxidative stress may play a key role in dementia. This is substantiated by the recent discovery of the protective effect of wine. In wine, the flavonoids--powerful antioxidant substances also contained in tea, fruits and vegetables--have been thought to offer such protection. We investigated whether flavonoid intake could be associated with a lower incidence of dementia in a cohort of 1367 subjects above 65 years of age (Paquid). A questionnaire was used to evaluate their intake of flavonoids and subjects were followed-up for 5 years between 1991 and 1996: 66 incident cases of dementia were observed. We estimated the relative risk (RR) of dementia according to tertiles of flavonoid intake using a Cox model. The age-adjusted RR of dementia was 0.55 for the two highest tertiles compared to the lowest (95% CI: 0.34-0.90; p = 0.02). After additional adjustment for gender, education, weight and vitamin C intake, the RR was 0.49 (95% CI: 0.26-0.92; p = 0.04). We conclude that the intake of antioxidant flavonoids is inversely related to the risk of incident dementia.

Aged↗
PubMed2000

Analysis of left-censored longitudinal data with application to viral load in HIV infection.

The classical model for the analysis of progression of markers in HIV-infected patients is the mixed effects linear model. However, longitudinal studies of viral load are complicated by left censoring of the measures due to a lower quantification limit. We propose a full likelihood approach to estimate parameters from the linear mixed effects model for left-censored Gaussian data. For each subject, the contribution to the likelihood is the product of the density for the vector of the completely observed outcome and of the conditional distribution function of the vector of the censored outcome, given the observed outcomes. Values of the distribution function were computed by numerical integration. The maximization is performed by a combination of the Simplex algorithm and the Marquardt algorithm. Subject-specific deviations and random effects are estimated by modified empirical Bayes replacing censored measures by their conditional expectations given the data. A simulation study showed that the proposed estimators are less biased than those obtained by imputing the quantification limit to censored data. Moreover, for models with complex covariance structures, they are less biased than Monte Carlo expectation maximization (MCEM) estimators developed by Hughes (1999) Mixed effects models with censored data with application to HIV RNA Levels. Biometrics 55, 625-629. The method was then applied to the data of the ALBI-ANRS 070 clinical trial for which HIV-1 RNA levels were measured with an ultrasensitive assay (quantification limit 50 copies/ml). Using the proposed method, estimates obtained with data artificially censored at 500 copies/ml were close to those obtained with the real data set.

Journal Article↗
PubMed1999

Prevalence of asthma and mean levels of air pollution: results from the French PAARC survey. Pollution Atomosphérique et Affections Respiratoires Chroniques.

Among the possible explanations for the recent increase in the prevalence of asthma in several countries, air pollution is one of the foremost public health concerns. Data from the "Pollution Atmosphérique et Affections Respiratoires Chroniques" (PAARC) survey collected in 24 areas of seven French towns during 1974-1976 were reanalysed to assess the relationship between the prevalence of asthma and the following air pollutants: sulphur dioxide (specific (SO2) and acidimetric methods), total suspended particles (TSP), black smoke (BS), nitrogen dioxide and nitric oxide. Correlation coefficients between annual mean levels of pollution and prevalence of asthma in the different areas were first calculated. Random-effects models were then estimated. Of the 20,310 adults aged 25-59 yrs, 1,291 (6.4%) were found to be asthmatics as well as 195 (6.1%) of the 3,193 children aged 5-9 yrs. A geographical correlation between asthma and annual mean level of SO2 (ranging 17-85 microg x m(-3)) was found (r=0.45, p=0.01) in adults. No relationship was found in children. After controlling for age, educational level, smoking, and geographical clustering with a multivariate random-effects model, the relationship remained significant in adults for SO2 (odds ratio for a 50 microg x m(-3) increase=1.24, confidence interval 1.08-1.44, p=0.0035). It also remained significant when taking into account only the people reporting their last asthma attack occurring after settling in the study area. These results are consistent with the known short-term effects of SO2 in asthma and demonstrate the necessity for further studies on delayed effects of air pollution in respiratory diseases.

Adult↗
PubMed1999

[Analysis of longitudinal Gaussian data with missing data on the response variable].

BACKGROUND: Using an application and a simulation study we show the bias induced by missing data in the outcome in longitudinal studies and discuss suitable statistical methods according to the type of missing responses when the variable under study is gaussian. METHOD: The model used for the analysis of gaussian longitudinal data is the mixed effects linear model. When the probability of response does not depend on the missing values of the outcome and on the parameters of the linear model, missing data are ignorable, and parameters of the mixed effects linear model may be estimated by the maximum likelihood method with classical softwares. When the missing data are non ignorable, several methods have been proposed. We describe the method proposed by Diggle and Kenward (1994) (DK method) for which a software is available. This model consists in the combination of a linear mixed effects model for the outcome variable and a logistic model for the probability of response which depends on the outcome variable. RESULTS: A simulation study shows the efficacy of this method and its limits when the data are not normal. In this case, estimators obtained by the DK approach may be more biased than estimators obtained under the hypothesis of ignorable missing data even if the data are non ignorable. Data of the Paquid cohort about the evolution of the scores to a neuropsychological test among elderly subjects show the bias of a naive analysis using all available data. Although missing responses are not ignorable in this study, estimates of the linear mixed effects model are not very different using the DK approach and the hypothesis of ignorable missing data. CONCLUSION: Statistical methods for longitudinal data including non ignorable missing responses are sensitive to hypotheses difficult to verify. Thus, it will be better in practical applications to perform an analysis under the hypothesis of ignorable missing responses and compare the results obtained with several approaches for non ignorable missing data. However, such a strategy requires development of new softwares.

Data Interpretation, Statistical↗
PubMed1998

Risk factors for fractures in the elderly.

We report the results of a 5-year prospective cohort study of risk factors for fractures, including drinking fluoridated water, in a cohort of 3,216 men and women aged 65 years and older. We studied risk factors for hip fracture and fractures at other locations separately. We found a higher risk of hip fractures for subjects exposed to fluorine concentrations over 0.11 mg per liter but without a dose-effect relation (odds ratio (OR) = 3.25 for a concentration of 0.11-0.25 mg per liter; OR = 2.43 for > or = 0.25 mg per liter]. For higher thresholds (0.7 and 1 mg per liter), however, the OR was less than 1. We found no association between fluorine and non-hip fractures. Non-hip fractures were associated with polymedication rather than with specific drug use, whereas fracture was associated with polymedication and use of anxiolytic and antidepressive drugs. Subjects drinking spirits every day were more likely to have hip fractures. Tobacco consumption increased the risk for non-hip fractures.

Age Factors↗
PubMed1997

Tests of geographical correlation with adjustment for explanatory variables: an application to dyspnoea in the elderly.

We propose a test of correlation of the residuals in generalized linear models which is a generalization of the spatial autocorrelation test based on Moran's I. It allows adjustment for sizes of geographical areas and for explanatory variables. A formula is given to compute the weights according to the alternative hypothesis. We compare inference using the distribution in the model and using the permutation distribution. A simulation study showed that the model-based test may be very conservative and this leads to a loss of power compared to the permutation test or to the model-based test with correction for estimated parameters. As this latter is intractable for very large samples when the model includes explanatory variables, we recommend the use of the permutation test. The permutation test is used to study geographical correlation of dyspnoea in the elderly.

Age Factors↗