One‐year survival of demented stroke patients: data from the Dijon Stroke Registry,France (1985–2008)

Background and purpose: Dementia is a frequent condition after stroke that may affect the prognosis of patients. Our aim was to determine whether post‐stroke dementia was a predictor of 1‐year case‐fatality and to evaluate factors that could influence survival in demented stroke patients. Methods: From 1985 to 2008, all first‐ever strokes were recorded in the population‐based stroke registry of Dijon, France (150 000 inhabitants). Dementia was diagnosed during the first month following stroke, according to DSM‐III and DSM‐IV criteria. Survival was evaluated at 1 year and multivariate analyses were performed using Cox proportional hazards to identify independent predictive factors. Results: We recorded 3948 first‐ever strokes. Among these stroke patients, 3201 (81%) were testable, and of these, 653 (20.4%) had post‐stroke dementia (337 women and 316 men). Demented patients had lower 1‐year survival than patients without dementia (82.9% vs. 86.9%, P = 0.013). However, in multivariate analysis, dementia did not appear as an independent predictor of 1‐year death. In demented stroke patients, age >80 years old, severe handicap at discharge, recurrent stroke within the first year and subarachnoid haemorrhage were associated with a higher risk of 1‐year death, and the risk was lower in the study period 2003–2008. Conclusions: Dementia after stroke is not independently associated with an increased risk of death at 1 year. In recent years, 1‐year case‐fatality decreased in demented as well as in and non‐demented patients suggesting that improvements in the management of stroke also benefited the most fragile patients.     

Effects of interleukin-2 therapy combined with highly active antiretroviral therapy on immune restoration in HIV-1 infection: a randomized controlled trial

BACKGROUND: Intermittent interleukin-2 (IL-2) therapy leads to a sustained increase of CD4 T cells in HIV-1-infected patients. METHODS: Symptom-free HIV-1-infected patients who were naive to all antiretroviral drugs (n = 68) and/or to protease inhibitors (n = 50) and had a CD4 cell count of 200-550 x 10(6) cells/l were randomly assigned to start lamivudine/stavudine/indinavir alone (controls) or combined from week 4 with subcutaneous IL-2 (5 x 10(6) IU twice daily for 5 days: every 4 weeks for three cycles, then every 8 weeks for seven cycles). Immunological and virological results were monitored until week 74. RESULTS: CD4 T cell counts increased more in the IL-2 group than in the controls (median increases 865 and 262 x 10(6) cells/l, respectively; P < 0.0001); an 80% increase in CD4 T cells was achieving by 89% of the IL-2 group and by 47% of the controls (P < 0.0001). Decrease of plasma viral loads was similar in both groups. Compared with controls, IL-2 induced a greater increase of naive and memory CD4 T cells, lymphocyte expression of CD28 and CD25 (P < 0.0001) and natural killer cells (P < 0.001). In a logistic regression analysis, odds of being responders to recall antigens was 8.5-fold higher in IL-2 recipients (P = 0.002) than in controls. The former experienced a higher level of antibody response to tetanus vaccination at week 64 than controls (32 and 8 haemagglutinating units/ml, respectively; P = 0.01). CONCLUSIONS: The combination of antiviral drugs and IL-2 induced a greater expansion and function of CD4 T cells than antiretroviral drugs alone.     

Effects of nicotine in the dopaminergic system of mice lacking the alpha4 subunit of neuronal nicotinic acetylcholine receptors

The mesostriatal dopaminergic system influences locomotor activity and the reinforcing properties of many drugs of abuse including nicotine. Here we investigate the role of the alpha4 nicotinic acetylcholine receptor (nAChR) subunit in mediating the effects of nicotine in the mesolimbic dopamine system in mice lacking the alpha4 subunit. We show that there are two distinct populations of receptors in the substantia nigra and striatum by using autoradiographic labelling with 125I alpha-conotoxin MII. These receptors are comprised of the alpha4, beta2 and alpha6 nAChR subunits and non-alpha4, beta2, and alpha6 nAChR subunits. Non-alpha4 subunit-containing nAChRs are located on dopaminergic neurons, are functional and respond to nicotine as demonstrated by patch clamp recordings. In vivo microdialysis performed in awake, freely moving mice reveal that mutant mice have basal striatal dopamine levels which are twice as high as those observed in wild-type mice. Despite the fact that both wild-type and alpha4 null mutant mice show a similar increase in dopamine release in response to intrastriatal KCl perfusion, a nicotine-elicited increase in dopamine levels is not observed in mutant mice. Locomotor activity experiments show that there is no difference between wild-type and mutant mice in basal activity in both habituated and non-habituated environments. Interestingly, mutant mice sustain an increase in cocaine-elicited locomotor activity longer than wild-type mice. In addition, mutant mice recover from depressant locomotor activity in response to nicotine at a faster rate. Our results indicate that alpha4-containing nAChRs exert a tonic control on striatal basal dopamine release, which is mediated by a heterogeneous population of nAChRs.     

An analysis of antiretroviral therapy outcomes in the Medecins Sans Frontieres/Guangxi Center for Disease Control and Prevention HIV/AIDS project

OBJECTIVE: To evaluate the 3-year outcomes of the Medecins Sans Frontieres/Guangxi Center for Disease Control and Prevention comprehensive and free of charge HIV/AIDS treatment and care project. METHODS: We present a detailed retrospective analysis of treatment outcomes of 432 cases who received highly active antiretroviral therapy (HAART) from December 2003 to December 2006. RESULTS: Among the adult patients who received HAART, the mortality rate was 6.5% and only 12 (2.8%) patients were lost to follow up. The mean CD4+ T cell count increase was 147 cells/microl and 246 cells/microl for patients receiving HAART for 9-15 and 21-27 months respectively. An adherence assessment conducted during March to December 2006 indicated that 95.9% of the study cases reached an adherence of 95% or more of the prescribed medications. Among the 30 children patients who received HAART, 4 (13.3%) cases died and the mean CD4+ T cell increase after 9-15 and 21-27 months of HAART was 673 cells/microl and 658 cells/microl respectively. 148 of the adult patients starting HAART were current or ex-intravenous drug users (IDU) and showed global death rate and lost to follow-up rate comparable to those of non-IDU patients (Log rank test, P = 0.91). CONCLUSIONS: Good mid-term therapeutic outcomes with combination antiretroviral therapy have been achieved in this project. Total free of charge care and treatment and intensive patient support/ counseling are crucial to program success.     

Immunological and virological efficacy of a therapeutic immunization combined with interleukin-2 in chronically HIV-1 infected patients

OBJECTIVE: Several lines of evidence suggest that the immune system may control HIV-1 replication, but that it could fail in the long term. Strategies aimed to elicit specific immune responses may enable patients to contain virus replication. METHODS: HIV-1-infected patients were randomized to continue either their antiviral therapy alone (controls; n = 37) or with four boosts of vaccination combining ALVAC-HIV (vCP1433) and Lipo-6T vaccines (weeks 0, 4, 8, 12) followed by three cycles of subcutaneous interleukin-2 (weeks 16, 24, 32) (Vac-IL-2 group; n = 34). RESULTS: Of the Vac-IL-2 group, 15/32 (47%) exhibited a stable HIV p24 antigen-proliferative response compared with 8/33 (24%) controls (P = 0.049). After vaccination, 19/33 (58%) of the Vac-IL-2 group exhibited a multiepitopic HIV-1-specific CD4 cell proliferative response compared with 9/36 (25%) of controls (P = 0.006). The breadth and the magnitude of HIV-specific interferon-gamma-producing CD8 T cells improved in the Vac-IL-2 group. After stopping antiviral drugs, 24% of the Vac-IL-2 group lowered their viral set point compared with 5% of controls (P = 0.027). Logistic-regression analysis demonstrated that vaccine-elicited immunological responses were predictive of virological control (P = 0.046 and 0.014 for stable and multiepitopic CD4 T cell responses, respectively). CONCLUSION: This study provides proof of the concept that therapeutic immunization before antiviral drug cessation may contribute to the containment of HIV replication.     

Long-term effects of intermittent interleukin-2 therapy in chronic HIV-infected patients (ANRS 048-079 Trials)

OBJECTIVE: Interleukin (IL)-2 therapy leads to significant CD4 cell increases in HIV-infected patients. Since phase III trials are ongoing, studies supporting the long-term feasibility of this strategy are needed. METHODS: We studied the long-term outcomes of 131 patients treated with IL-2 in two studies initiated either before (ANRS 048) or following (ANRS 079) the advent of HAART. RESULTS: At the last assessment (median follow-up 3.4 years), these patients experienced a gain of 428 cells/microl and a decrease in plasma HIV RNA to 1.70 log10 copies/ml. In both studies, high CD4 cell counts were maintained with a median of ten 5-day cycles of subcutaneous IL-2. Median time since the last cycle was 2 years. At last assessment, 59% of 048 patients maintained a non-HAART regimen. Detailed analysis at week 170 showed that median CD4 cell counts were 856 (048) and 964 (079) cells/microl. This corresponded to a gain from baseline of 515 (048) and 627 (079) cells/microl. The median viral load decreases from baseline and corresponded to 1.70 (048) and 1.88 (079) log10 copies/ml. Comparisons across the studies showed that CD4 gains and viral load changes were similar whether HAART or non-HAART was used. The frequency of cycling, but not CD4 cell counts, viral loads or antiviral regimen at baseline, was predictive of long-term CD4 gain (P = 0.03). CONCLUSION: Altogether, these observations support IL-2 as a long-term therapeutic strategy in HIV infection.     

Decrease in the stroke case fatality rates in a French population-based twenty-year study. A comparison between men and women

BACKGROUND: The aim of the study was to estimate trends in stroke case fatality in a French population-based study over the last 20 years, and to compare trends in men and women. METHODS: We prospectively ascertained first-ever strokes in a well-defined population-based study, from 1985 to 2004, in Dijon (France) (150,000 inhabitants). The study was both specific and exhaustive. The follow-up made it possible to analyze case fatality, according to stroke subtypes and sex. RESULTS: From the ascertainment of 3,691 strokes divided in 1,920 cerebral infarcts from large artery atheroma, 725 cerebral infarcts from small perforating artery atheroma, 497 cardioembolic infarcts, 134 cerebral infarcts from undetermined mechanism, 341 primary cerebral hemorrhages and 74 subarachno?d hemorrhages, we observed a significant decrease in 28-day case fatality rates of almost 25% (p = 0.03). Case fatality rates decreased in men aged >75 years (p = 0.01) and in women aged >75 years (p = 0.02) and >65 years (p = 0.03). The magnitude of the decrease was smaller in women but not significantly so. According to stroke subtypes, case fatality rates significantly decreased for small perforating artery infarct (p = 0.04) and for primary cerebral hemorrhage (p = 0.03). In multivariate regression analyses, hemorrhagic stroke, the first period of the study (1985-1989), blood hypertension, previous myocardial infarction and age <85 years had a negative effect. CONCLUSION: This is the first population-based study using continuous ascertainment over a period of 20 years that has demonstrated a significant reduction in case fatality rates. We did not observe any significant differences between men and women.     

Trends in the incidence of transient ischemic attacks, premorbid risk factors and the use of preventive treatments in the population of Dijon, France from 1985 to 2004

BACKGROUND: We describe the epidemiological trends of transient ischemic attack (TIA) in a 20-year population-based pilot study. METHODS: Trends in the incidence, risk factors and pre-TIA use of preventive treatments for TIA were observed from 1985 to 2004 according to the classic definition in the population of the city of Dijon, France (150,000 inhabitants). RESULTS: The raw and standardized incidence of TIA were stable over time. We observed a significant increase in the mean age at TIA onset in women only. The prevalence of hypercholesterolemia and diastolic blood pressure > or =90 mm Hg among patients with TIA increased significantly. This contrasts with falls in smoking and in history of previous myocardial infarction. CONCLUSION: The stability of classic TIA incidence, despite the rise in the proportion of elderly people, and the increase in the mean age at onset in women may be considered as a medical progress.     

Knowledge,attitudes, and practices regarding antiretroviral management,reproductive health,sexually transmitted infections,and sexual risk behavior among perinatally HIV-infected youth in Thailand

More than 30% of perinatally HIV-infected children in Thailand are 12 years and older. As these youth become sexually active, there is a risk that they will transmit HIV to their partners. Data on the knowledge, attitudes, and practices (KAP) of HIV-infected youth in Thailand are limited. Therefore, we assessed the KAP of perinatally HIV-infected youth and youth reporting sexual risk behaviors receiving care at two tertiary care hospitals in Bangkok, Thailand and living in an orphanage in Lopburi, Thailand. From October 2010 to July 2011, 197 HIV-infected youth completed an audio computer-assisted self-interview to assess their KAP regarding antiretroviral (ARV) management, reproductive health, sexual risk behaviors, and sexually transmitted infections (STIs). A majority of youth in this study correctly answered questions about HIV transmission and prevention and the importance of taking ARVs regularly. More than half of the youth in this study demonstrated a lack of family planning, reproductive health, and STI knowledge. Girls had more appropriate attitudes toward safe sex and risk behaviors than boys. Although only 5% of the youth reported that they had engaged in sexual intercourse, about a third reported sexual risk behaviors (e.g., having or kissing boy/girlfriend or consuming an alcoholic beverage). We found low condom use and other family planning practices, increasing the risk of HIV and/or STI transmission to sexual partners. Additional resources are needed to improve reproductive health knowledge and reduce risk behavior among HIV-infected youth in Thailand.