The objective of the study was to describe the evolution of chronic non-AIDS related diseases and their risk factors, in patients living with HIV (PLHIV) in the French ANRS CO3 Aquitaine prospective ...cohort, observed both in 2004 and in 2014 in order to improve long-term healthcare management.
The ANRS CO3 Aquitaine cohort prospectively collects epidemiological, clinical, biological and therapeutic data on PLHIV in the French Aquitaine region. Two cross sectional analyses were performed in 2004 and 2014, to investigate the patient characteristics, HIV RNA, CD4 counts and prevalence of some common comorbidities and treatment.
2138 PLHIV (71% male, median age 52.2 years in 2014) were identified for inclusion in the study, including participants who were registered in the cohort with at least one hospital visit recorded in both 2004 and 2014. Significant increases in the prevalence of diagnosed chronic kidney disease (CKD), bone fractures, cardiovascular events (CVE), hypertension, diabetes and dyslipidaemia, as well as an increase in treatment or prevention for these conditions (statins, clopidogrel, aspirin) were observed. It was also reflected in the increase in the proportion of patients in the "high" or "very high" risk groups of the disease risk scores for CKD, CVE and bone fracture score.
Between 2004 and 2014, the aging PLHIV population identified in the French ANRS CO3 Aquitaine prospective cohort experienced an overall higher prevalence of non-HIV related comorbidities, including CKD and CVD. Long-term healthcare management and long-term health outcomes could be improved for PLHIV by: careful HIV management according to current recommendations with optimal selection of antiretrovirals, and early management of comorbidities through recommended lifestyle improvements and preventative measures.
A multi-particulate fixed-dose combination product, consisting of a combination of two alkalising salts formulated as prolonged-release granules, ADV7103, was developed to obtain a sustained and ...prolonged alkalising effect. The specific release of both types of granules was shown in vitro through their dissolution profiles, which indicated that potassium citrate was released within the first 2-3 h and potassium bicarbonate up to 10-12 h after administration. The long-lasting coverage of ADV7103 was confirmed through a randomised, placebo-controlled, double-blind, two-period study, measuring its effect on urine pH in healthy adults (n = 16) at doses of alkalising agent ranging between 0.98 and 2.88 meq/kg/day. A significant increase of urine pH with a positive dose-response in healthy adult subjects was shown. Urine pH above 7 was maintained during 24 h with a dosing equivalent to 1.44 meq/kg twice a day, while urine pH was below 6 most of the time with placebo. The effect observed was non-saturating within the range of doses evaluated and the formulation presented a good safety profile. ADV7103 provided an effective prolonged release of alkalising salts to cover a 12-h effect with adequate tolerability and could afford a twice a day (morning and evening) dosing in patients requiring long-term treatment.
Assessing disease activity in patients suffering from autoimmune diseases is complex. Symptoms are multiple, often subjective and there are no reliable biomarkers. Many activity scores have been ...implemented to compare treatment efficacy in clinical trials. Their use in clinical practice is largely unknown. We performed a practical survey to analyze the use of activity scores in clinical practice to consider treatment response and to assess the determinants of their use.
A sample of French internists answered a questionnaire about activity scores of systemic lupus erythematosus, Sjögren's syndrome, autoimmune myositis and necrotizing vasculitis of small vessels. The frequency of use of these tools, the causes of their non-use, and the general opinion of practitioners about the place of theses scores in current practice were described.
The form was completed by 92 internists. Seventy percent of them supported the use of activity scores in consultations, but actually used them in less than 25% of patient visits. The reasons for the low use of these scores are mainly the ignorance of their existence (42%) and their length or complexity (28%).
The discrepancy between the ratio of practitioners who believe that scores have a place in daily practice and their actual use shows that the current scores do not meet the needs. The implementation of easily usable activity scores in inflammatory diseases remains a challenge for the internists.
The aim of the paper is to describe the characteristics of postmenopausal HIV-infected women and to investigate the factors associated with an earlier onset of menopause in a hospital-based cohort. ...Information was collected using a self-administered questionnaire. A Cox model was used to determine factors associated with menopause. Among the 404 women who completed the questionnaire, 69 were naturally postmenopausal at the time of the study (median age at onset: 49 years, premature menopause <40 years: 12%). The onset of menopause was studied among the 41 women still menstruating at the enrollment in the cohort, and who experienced menopause during follow-up. African origin (hazard ratio HR = 8.16; 95% confidence interval CI = 2.23-29.89) and history of injecting drug use (IDU) (HR = 2.46; 95% CI = 1.03-5.85) were associated with an increased risk of earlier menopause. Women with a CD4 cell count <200 cells/mm(3) tended to reach menopause earlier (HR = 2.25; 95% CI = 0.94-5.39). Earlier occurrence of menopause seems to be associated with factors already reported in HIV-negative women (IDU, ethnicity) and with HIV-related immunodeficiency.
Co-stimulatory molecule cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibits T-cell activation. Clinically, CTLA-4 has been targeted in opposite ways: its blockade enhances antitumor immunity in the ...field of oncology, whereas CTLA-4 agonists such as abatacept are used for the treatment of immuno-inflammatory diseases as rheumatoid arthritis (RA).
We herein report the case of a 69-year-old man with a history of severe RA successfully treated with abatacept, who showed unusually rapid progression of undifferentiated multi-metastatic carcinoma.
Although no significant increase in malignancy has been reported in abatacept-treated patients, several case reports have documented the possible association with the acceleration of the progression of malignancy. Here, abatacept may have altered immune surveillance and hence allowed tumor growth.
Recent research has demonstrated that parental behaviors have an important impact upon child and adolescent pain outcomes. At present, however, we do not know which parents engage in particular ...behaviors and why. In 2 studies, the impact of parental catastrophizing about their child's pain upon parental tendency to stop their child's pain-inducing activity was investigated. Further, the mediating role of parental distress was explored. In study 1, a sample of schoolchildren (n=62; M=12.48 years; SD=1.72) took part in a cold-pressor task. In study 2, a clinical sample of adolescents with chronic pain (n=36; M=15.68 years; SD=1.85) performed a 2-min walking task designed as a pain-inducing activity. In both studies, the accompanying parent was asked to watch their child performing the pain task. Findings revealed, for both studies, that parents with a high level of catastrophic thinking about their child's pain experienced more distress and a greater behavioral tendency of wanting to stop their child's pain-inducing activity. Further, parental feelings of distress mediated the relationship between parental catastrophic thinking and parents' tendency to restrict their child's activity. The findings are discussed in light of an affective-motivational conceptualization of pain and pain behavior. Parental catastrophizing was associated with parental tendency to restrict their child's engagement in a painful test, and this relationship was mediated by parental distress.
The identification of densification mechanism during hot uniaxial pressing is developed using an approach based on classical creep investigation. This approach is justified and generalised using ...continuum mechanics based sintering models. The benefit of this approach is to directly determine the densification parameters from the analysis of shrinkage rates of the porous material, rather than to transpose the creep mechanisms identified for dense material at given thermomechanical conditions to the densification progress. The suggested approach is applied to compare the densification mechanisms involved at the initial stage of sintering (i.e. for 60 % < relative density < 75 %) during hot pressing (HP) and spark plasma sintering (SPS) of a submicrometric alpha-alumina powder. From the stress exponent and activation energy values, it is shown that the main mechanism involves grain boundary sliding accommodated by dislocation motion and particle fracture in both cases. However, it appears that, in SPS, the high heating rate could reduce the existence of surface diffusion phenomena at the beginning of the consolidation process, as suggested by the higher activation energy compared to the one determined for HP.
Therapeutic control of HIV replication reduces the size of the viral reservoir, particularly among central memory CD4+ T cells, and this effect might be accentuated by early treatment.
We examined ...the effect of ART initiated at the time of the primary HIV infection (early ART), lasting 2 and 6 years in 11 and 10 patients, respectively, on the HIV reservoir in peripheral resting CD4+ T cells, sorted into naive (TN), central memory (TCM), transitional memory (TTM) and effector memory (TEM) cells, by comparison with 11 post-treatment controllers (PTCs).
Between baseline and 2 years, CD4+ T cell subset numbers increased markedly (P < 0.004) and HIV DNA levels decreased in all subsets (P < 0.009). TTM cells represented the majority of reservoir cells at both timepoints, T cell activation status normalized and viral diversity remained stable over time. The HIV reservoir was smaller after 6 years of early ART than after 2 years (P < 0.019), and did not differ between PTCs and patients treated for 6 years. One patient, who had low reservoir levels in all T cell subsets after 2 years of treatment similar to the levels in PTCs, spontaneously controlled viral replication during 18 months off treatment.
Early prolonged ART thus limits the size of the HIV reservoir, protects long-lived cells from persistent infection and may enhance post-treatment control.
Various carbonated calcium phosphate powders were synthesized by aqueous precipitation and ceramics consolidation by spark plasma sintering (SPS) at very low temperature was investigated. The ...objective was to preserve low crystallinity and avoid material decarbonation. SPS at low temperature only leads to little or no sintering when crystallized powders are used. Amorphous powders are required. In this case, consolidation occurs at temperatures below 150°C. It is accompanied by crystallization of the amorphous phase into calcium-deficient carbonated apatite Ca10-x-y(PO4)6-x-y(HPO4)x(CO3)y(OH)2-x-y-2z(CO3)z. The resulting ceramics are microporous and highly cohesive with good mechanical properties (flexural strength=18MPa). The sintering mechanism, called “crystal fusion”, is based on solid state diffusion of chemical species at the grain boundary and crystal growth within the amorphous particles. These bioceramics that mimic the composition of the bone mineral are expected to have a higher bioreactivity than well crystallized carbonated hydroxyapatite ceramics obtained by conventional sintering.
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