Exposure to psychotropics in the French older population living with dementia: a nationwide population-based study.

BACKGROUND: Little is known about the level of psychotropic chronic exposure in all patients living with dementia. The aim of the study was to quantify chronic psychotropic exposure in older adults with dementia compared with the general population of the same age. METHODS: This prospective cohort study was conducted in France between 2009 and 2011. Aged at least 65 years, 10,781,812 individuals (440,215 of them with dementia) either community based or nursing home residents were included. The numbers of single or combined prescriptions, per year for antipsychotics, antidepressants, anxiolytics, or hypnotics were measured. RESULTS: Of patients with dementia, 15.5% are exposed to antipsychotics compared with 2.2% of the age-matched population (relative risk [RR] = 6.44, 95% confidence interval [CI] [6.39-6.48]), 39.5% to antidepressants compared with 12.6% (RR = 4.10, 95% CI [.4.07-4.12]), and 39.6% to anxiolytics or hypnotics compared with 26.9% (RR = 1.74, 95% CI [1.72-1.75]). Among older adults with dementia, 13.8% simultaneously consumed at least three psychotropics. All class age of older patients with dementia is more exposed to all psychotropics except for long-acting benzodiazepines. During the study period, chronic anxiolytic/hypnotic and antipsychotic exposure slightly decreased in population with dementia while chronic exposure to antidepressant drugs tended to increase. CONCLUSION: This nationwide, population-based, drug-used study showed for the first time that older patients with dementia are chronically overexposed not only to antipsychotics but also to psychotropics.

Sharing knowledge to advance healthcare policies in Europe for people living with dementia and their carers: the ALCOVE project.

BACKGROUND: Alzheimer's disease and other related dementias are public health priorities in the European Union due to their prevalence, cost and profound impact on society. Because of these pressing implications, the European Union decided to create a Joint Action to share knowledge about dementia and health policy in order to preserve the health, quality of life, autonomy and dignity of people living with dementia and their carers in Europe. METHODS: ALCOVE is a European Community-funded Joint Action coordinated by the HAS (French National Authority for Health) with a 24-month duration. The project's life cycle has been divided into the following four steps: (1) collection of existing information, (2) analysis of existing information and making comparisons across Member States, (3) identifying Evidence, Needs, and Priorities, (4) drafting recommendations and disseminating them. RESULTS: 19 countries are participating in the ALCOVE initiative. The project will publish its final findings in 2013. The project's objectives, participants, method, on-going procedures and work plans are already available on the ALCOVE website: http://www.alcove-project.eu/. Preliminary results show that recommendations will need to focus on clinical and epidemiological data collection, diagnostic system assessment, outstanding approaches for treating behavioural disorders, limiting antipsychotic use, and competence assessment in this vulnerable population. CONCLUSIONS: The European Member States involved are mobilized to share best health policy practices in order to tackle the challenge of dementia's threat on European health and social systems and to improve the quality of life and care for individuals and their family carers.

Ex vivo pharmacodynamics of amoxicillin-clavulanate against beta-lactamase-producing Escherichia coli in a yucatan miniature pig model that mimics human pharmacokinetics.

The objective of the present study was to investigate the potential bactericidal activity of amoxicillin-clavulanate against beta-lactamase-producing Escherichia coli strains and to elucidate the extent to which enzyme production affects the activity. Six adult Yucatan miniature pigs received a single intravenous dose of 1.1 g of amoxicillin-clavulanate as an intravenous infusion over 30 min. The pharmacokinetic parameters were determined for the serum samples and compared to the published data for humans (2.2-g intravenous dose). The parameters were comparable for the two species, and therefore, the miniature pig constitutes a good model for pharmacodynamic study of amoxicillin-clavulanate. Therefore, the model was used in an ex vivo pharmacodynamic study of amoxicillin-clavulanate against four strains of Escherichia coli producing beta-lactamases at different levels. The E. coli strains were cultured with serial dilutions (1:2 to 1:256) of the serum samples from the pharmacokinetic study, and the number of surviving bacteria was determined after 1, 3, and 6 h of exposure. Amoxicillin-clavulanate at concentrations less than the MIC and the minimal bactericidal concentration had marked bactericidal potency against the strain that produced low levels of penicillinase. For high-level or intermediate-level beta-lactamase-producing strains, the existence of a clavulanate concentration threshold of 1.5 to 2 micro g/ml, below which there was no bactericidal activity, was demonstrated. The index of surviving bacteria showed the existence of mixed concentration- and time-dependent actions of amoxicillin (in the presence of clavulanate) which varied as a function of the magnitude of beta-lactamase production by the test strains. This study shows the effectiveness of amoxicillin-clavulanate against low- and intermediate-level penicillinase-producing strains of E. coli. These findings are to be confirmed in a miniature pig experimental infection model.