Jean-Marc Lacombe

Relationship between blood pressure and outdoor temperature in a large sample of elderly individuals: the Three-City study.

BACKGROUND Seasonal variations of blood pressure-related diseases have been described in several populations. However, few studies have examined the seasonal variations of blood pressure in the elderly, a segment of the population particularly exposed to vascular diseases. The association of blood pressure with season and outdoor temperature was examined in 8801 subjects 65 years or older from the Three-City study, a population-based longitudinal study. METHODS Blood pressure was measured at baseline and 2-year follow-up examinations. Daily outdoor temperature measured at 11 am was provided by the local meteorological offices. RESULTS Both systolic and diastolic blood pressure values differed significantly across the 4 seasons and across the quintiles of the distribution of outdoor temperature. Systolic blood pressure decreased with increasing temperature, with an 8.0-mm Hg decrease between the lowest (< 7.9 degrees C) and the highest (> or = 21.2 degrees C) temperature quintile. Intraindividual differences in blood pressure between follow-up and baseline examinations were strongly correlated with differences in outdoor temperature. The higher the temperature at follow-up compared with baseline, the greater the decrease in blood pressure. Longitudinal changes in blood pressure according to difference in outdoor temperature were larger in subjects 80 years or older than in younger participants. CONCLUSIONS Outdoor temperature and blood pressure are strongly correlated in the elderly, especially in those 80 years or older. During periods of extreme temperatures, a careful monitoring of blood pressure and antihypertensive treatment could contribute to reducing the consequences of blood pressure variations in the elderly.

Prevalence, awareness, treatment, and control of hypertension in the elderly: the Three City study.

Objective To study management of hypertension in the elderly in a large population-based study and to evaluate the prevalence of hypertension and factors related to awareness, treatment, and control. Design The Three City study, a population-based study among 9693 non-institutionalized individuals aged 65 years and over. Methods Blood pressure was measured with an automated electronic device, and treatment assessed, during home interview. Hypertension was defined by a mean blood pressure of two measurements superior to or equal to 160/95 mmHg and/or the intake of antihypertensive medications. Results In the final working sample of 9090 people, 62% were hypertensive. More than two-thirds were aware of their hypertension and 81% were treated with antihypertensive drugs. Among 4573 treated hypertensive participants, 35% had a blood pressure over 160/95 mmHg and 69% over 140/90 mmHg. Women were more frequently aware of their hypertension, more frequently treated, and more frequently controlled than men. A history of cardiovascular disease, high body mass index, diabetes and high frequency of visits to the general practitioner were related to higher percentages of awareness and treatment. Among treated hypertensive patients, those with a history of cardiovascular events or who visited their general practitioner more often or who more often had their blood pressure measured were more frequently controlled. Awareness was strongly associated with treatment, but was inversely related to control of hypertension among treated hypertensive patients. Conclusions Management of hypertension, and particularly its control among treated hypertensive patients, needs to be improved in people aged 65 years and over.

Relationship between blood pressure and depression in the elderly. The Three-city Study

Objective To examine the relationship between blood pressure and depression in a large sample of noninstitutionalized elderly people. Methods Cross-sectional community-based study in 9294 participants aged 65 years and over, living at home, in three French cities (Bordeaux, Dijon and Montpellier). Participants were categorized as depressive, based on three different markers of depression. Multiple linear regression analyses of the relation between depression and mean systolic and diastolic blood pressure values were conducted, taking into account potential confounders like age, sex, education, smoking, alcohol consumption, body mass index and history of cardiovascular events. Results Our working sample had a mean age (SD) of 73.7 (5.0) years, and included 60.7% of women. Overall, 31% of participants met the criteria for depression, 77.5% had hypertension, and 49.5% were on antihypertensive drugs. Analyses showed lower systolic and diastolic blood pressure values in depressive individuals compared with nondepressive ones, in both men (systolic blood pressure 148.2 versus 151.8 mmHg, P < 0.002; diastolic blood pressure 83.0 versus 84.7 mmHg, P = 0.003) and women (systolic blood pressure 141.7 versus 144.7 mmHg, P < 0.0001; diastolic blood pressure 80.7 versus 81.4 mmHg, P < 0.02). These associations were independent of age and of use of antihypertensive or psychotropic agents. Conclusion In a large sample of elderly individuals from the general population, depressive individuals had lower blood pressure values than nondepressive ones, independent of medications and of history of cardiovascular events.

Cohort Profile: French hospital database on HIV (FHDH-ANRS CO4)

The French Hospital Database on HIV (FHDH) is a hospital-based multicentre open cohort with inclusions ongoing since 1989. The research objectives focus mainly on mid- and long-term clinical outcomes and therapeutic strategies, as well as severe AIDS and non-AIDS morbidities, and public health issues relative to HIV infection. FHDH also serves to describe HIV-infected patients receiving hospital care in France. FHDH includes data on more than 120,000 HIV-infected patients from 70 French general or university hospitals distributed throughout France. Patients are eligible for inclusion if they are infected by HIV-1 or HIV-2 and give their written informed consent. Standardized variables are collected at each outpatient visit or hospital admission during which a new clinical manifestation is diagnosed, a new treatment is prescribed or a change in biological markers is noted, and/or at least every 6 months. Since its inception, variables collected in FHDH include demographic characteristics, HIV-related biological markers, the date and type of AIDS and non AIDS-defining events, antiretroviral treatments and the date and causes of death, as reported in the medical records. Since 2005, data have also been collected on: co-infection with hepatitis B or C virus; alcohol and tobacco use; and non HIV-related biomarkers. Anyone can submit a research project by completing a standardized form available on the FHDH website (http://www.ccde.fr/_fold/fl-1385734776-429.pdf) or from the corresponding author, describing the context and objectives of the study. All projects are reviewed by the scientific committee.

Memantine therapy for Alzheimer disease in real-world practice: an observational study in a large representative sample of French patients.

Clinical trials have shown modest effects of memantine, an N-methyl-D aspartate receptor antagonist, in Alzheimer disease patients and memantine effectiveness in routine clinical practice needs to be established further. In 2003, memantine was recommended in France for Alzheimer disease patients with disease severity ranging from 15 to 3 on the mini-mental state examination at the first prescription. Our study aimed at describing memantine use in real-world practice in a cohort of 5283 memantine-treated patients (mean age: 80.1 y; women: 69.4%) randomly selected from the database of the national healthcare insurance, which covers 70% of the French elderly population. Mean follow-up after starting memantine prescription was 10.4 months (range: 1 to 20 mo). Patients were older and had a less severe cognitive impairment than patients included in the first controlled clinical trials. Memantine was prescribed with a cholinesterase inhibitor in 53.3% of cases. At 6 months, 26% of the patients had stopped memantine therapy (36% at 12 mo); conversely, patients who continued treatment were highly compliant. The 1-year mortality rate (12.5%) was similar for a comparative cohort of untreated demented patients and the memantine-treated ones. Approximately one-third of the memantine-treated patients did not strictly fit with the French summary of product characteristic recommendations for the first memantine prescription.

Evaluation of the impact of memantine treatment initiation on psychotropics use: a study from the French national health care database.

Background: Clinical studies reported that treatments for Alzheimer’s disease may have an impact on behavioral and psychiatric disorders. We tested the hypothesis that memantine treatment initiation modifies psychotropic medication in real-life practice patients. Methods: A 2-year follow-up cohort study was performed. A sample of patients treated in the general population, extracted from the database of the French national healthcare system (CNAM-TS), was examined. The sample included 4,600 memantine-treated patients (mean age 79.8 years, 69% women) randomly selected from the database of the CNAM-TS covering 69% of the French population aged 65 years and over. The follow-up rate was 95.0%. This database includes exhaustive data on drug consumption. We used interrupted time series analysis of the proportion of psychotropics users (all psychotropic drugs and specific categories) before and after onset of memantine. Results: There was a 39–50% regular increase in patients treated with psychotropic drugs before memantine initiation This increasing trend stopped after memantine initiation, the proportion of psychotropic users remaining stable around 53% up to the end. The trends before and after memantine onset were significantly different (p < 0.001). Conclusions: Our results suggest a temporal relationship between the onset of memantine and the stabilization of psychotropic drugs use in this large sample of elderly patients.

Risk of Kaposi sarcoma during the first months on combination antiretroviral therapy

Objective:To determine whether incident AIDS-defining Kaposi sarcoma or Pneumocystis jiroveci pneumonia (PJP) is associated with combination antiretroviral therapy (cART) initiation. Design:Compare risk for Kaposi sarcoma and PJP by time on cART and CD4 reconstitution. Methods:In the FHDH-ANRS CO4 cohort (N = 66 369), Kaposi sarcoma (N = 1811) and PJP (N = 1718) incidence rates were computed by demographic and HIV strata. Crude and adjusted relative risk (RR) with 95% confidence intervals (CIs) following cART initiation were calculated by Poisson regression with untreated patients during 1996–2009 as reference. CD4 cell counts were compared by Wilcoxon rank sum tests. Results:The risk of Kaposi sarcoma was very high during months 1–3 on cART (N = 160, RRCrude 3.94, 95% CI 3.26–4.76), which was incompletely attenuated by adjustment for demographics and contemporaneous CD4 cell count (RRAdj 1.25, 95% CI 1.02–1.53). Corresponding PJP risk was minimally elevated (N = 84, RRCrude 1.80, 95% CI 1.42–2.30) and markedly reduced with adjustment on the same variables and PJP prophylaxis (RRAdj 0.52, CI 0.41–0.67). HIV load had no added effect. Median CD4 cell count at cART initiation was much lower in patients with incident Kaposi sarcoma (82 cells/&mgr;l) or PJP (61 cells/&mgr;l) within 3 months than in those who did not develop these conditions (>250 cells/&mgr;l). Notably, median CD4 cell count change was +44 cells/&mgr;l per month with incident Kaposi sarcoma within 3 months of cART initiation versus 0 cells/&mgr;l per month with incident PJP (P = 0.0003). Conclusion:Failure of CD4 cell count reconstitution during months 1–3 on cART fully accounted for incident PJP. In contrast, there were 1.6 additional Kaposi sarcoma cases per 1000 person-years during months 1–3 on cART, suggesting that immune reconstitution may contribute to the risk for AIDS-defining Kaposi sarcoma.

Looking Beyond the Cascade of HIV Care to End the AIDS Epidemic: Estimation of the Time Interval From HIV Infection to Viral Suppression.

Background:Ensuring early universal access to HIV treatment is critical to reach the end of AIDS. The cascade of HIV care has become a critical metric to assess the coverage of treatment and viral suppression, but it does not provide any information on the elapsed times between becoming HIV-infected and reaching viral suppression. Methods:We estimated the cascade of care, the distribution of times between steps of the care continuum, in France, in 2010, at the national level, overall and by HIV exposure groups, using statistical modelling and large datasets: the national HIV surveillance system, the general social insurance scheme, and the French Hospital Database on HIV. Results:We found that the overall rate of viral suppression was high, with an estimated value of 52% (95% confidence interval: 49 to 54). However, the time intervals from HIV infection to viral suppression were long; overall, the median value was 6.1 years (inter quartile range: 3.6–9.2), and it ranged from ∼5.6 years among men who have sex with men and heterosexual women to 9.6 years among injection drug users. Time lost in achieving viral suppression was mainly due to delays in HIV testing (overall median of 3.4 years), except for injection drug users where it was also due to delayed care entry once diagnosed (∼1 year in median versus <1 month for other groups). Conclusions:High viral suppression rate can hide large gaps between time of HIV infection and time of viral suppression. Estimates of the flow-time between steps of the care continuum should become priority indicators to identify these gaps and monitor whether interventions are successful in closing them.

CD4+ cell count recovery in naïve patients initiating cART, who achieved and maintained plasma HIV-RNA suppression.

A key objective of combined antiretroviral therapy (cART) is to reach and maintain high CD4 cell counts to provide long‐term protection against AIDS‐defining opportunistic infections and malignancies, as well as other comorbidities. However, a high proportion of patients present late for care. Our objective was to assess CD4 cell count recovery up to seven years in naïve patients initiating cART with at least three drugs in usual clinical care.

Is Impact of Statin Therapy on All-Cause Mortality Different in HIV-Infected Individuals Compared to General Population? Results from the FHDH-ANRS CO4 Cohort.

Background The effect of statins on all-cause mortality in the general population has been estimated as 0.86 (95%CI 0.79-0.94) for primary prevention. Reported values in HIV-infected individuals have been discordant. We assessed the impact of statin-based primary prevention on all-cause mortality among HIV-infected individuals. Methods Patients were selected among controls from a multicentre nested case-control study on the risk of myocardial infarction. Patients with prior cardiovascular or cerebrovascular disorders were not eligible. Potential confounders, including variables that were associated either with statin use and/or death occurrence and statin use were evaluated within the last 3 months prior to inclusion in the case-control study. Using an intention to continue approach, multiple imputation of missing data, Cox’s proportional hazard models or propensity based weighting, the impact of statins on the 7-year all-cause mortality was evaluated. Results Among 1,776 HIV-infected individuals, 138 (8%) were statins users. During a median follow-up of 53 months, 76 deaths occurred, including 6 in statin users. Statin users had more cardiovascular risk factors and a lower CD4 T cell nadir than statin non-users. In univariable analysis, the death rate was higher in statins users (11% vs 7%, HR 1.22, 95%CI 0.53-2.82). The confounders accounted for were age, HIV transmission group, current CD4 T cell count, haemoglobin level, body mass index, smoking status, anti-HCV antibodies positivity, HBs antigen positivity, diabetes and hypertension. In the Cox multivariable model the estimated hazard ratio of statin on all-cause mortality was estimated as 0.86 (95%CI 0.34-2.19) and it was 0.83 (95%CI 0.51-1.35) using inverse probability treatment weights. Conclusion The impact of statin for primary prevention appears similar in HIV-infected individuals and in the general population.