Gériatrie [Review in geriatric medicine 2014].

Several studies contributed to improving the diagnostic and prognostic assessment of delirium in hospitalized older patients. Direct patient education proved efficient in benzodiazepines withdrawal. A position statement of the American Geriatrics Society does not recommend tube feeding when eating difficulties arise in older persons suffering from advanced dementia. Several studies emphasized once again the potential importance of preventative interventions (in particular physical activity) to prevent or delay dementia occurrence. Two randomized controlled trials of monoclonal antibodies that bind amyloid did not show benefit in patients with mild-to-moderate Alzheimer's dementia (AD). In contrast, vitamin E reduced functional decline in these patients, and citalopram reduced agitation among AD patients as well as their caregiver's stress.

Évaluation d'une structure gériatrique entre l'ambulatoire et l'hospitalier [Geriatric institutions, between ambulatory and hospital care: patients' description and performance assessment].

Introduction : Décrire les patients d'une structure gériatrique offrant des hospitalisations de courte durée, dans un contexte ambulatoire, pour des situations gériatriques courantes dans le canton de Genève (Suisse). Mesurer les performances de cette structure en termes de qualité des soins et de coûts. Méthodes : Des données relatives au profil des 100 premiers patients ont été collectées (huit mois), ainsi qu'aux prestations, aux ressources et aux effets (réadmissions, décès, satisfaction, complications) de manière à mesurer différents indicateurs de qualité et de coûts. Les valeurs observées ont été systématiquement comparées aux valeurs attendues, calculées à partir du profil des patients. Résultats : Des critères d'admission ont été fixés pour exclure les situations dans lesquelles d'autres structures offrent des soins mieux adaptés. La spécificité de cette structure intermédiaire a été d'assurer une continuité des soins et d'organiser d'emblée le retour à domicile par des prestations de liaison ambulatoire. La faible occurrence des réadmissions potentiellement évitables, une bonne satisfaction des patients, l'absence de décès prématurés et le faible nombre de complications suggèrent que les soins médicaux et infirmiers ont été délivrés avec une bonne qualité. Le coût s'est révélé nettement plus économique que des séjours hospitaliers après ajustement pour la lourdeur des cas. Conclusion : L'expérience-pilote a démontré la faisabilité et l'utilité d'une unité d'hébergement et d'hospitalisation de court séjour en toute sécurité. Le suivi du patient par le médecin traitant assure une continuité des soins et évite la perte d'information lors des transitions ainsi que les examens non pertinents. INTRODUCTION: To describe patients admitted to a geriatric institution, providing short-term hospitalizations in the context of ambulatory care in the canton of Geneva. To measure the performances of this structure in terms of quality ofcare and costs. METHOD: Data related to the clinical,functioning and participation profiles of the first 100 patients were collected. Data related to effects (readmission, deaths, satisfaction, complications), services and resources were also documented over an 8-month period to measure various quality and costindicators. Observed values were systematically compared to expected values, adjusted for case mix. RESULTS: Explicit criteria were proposed to focus on the suitable patients, excluding situations in which other structures were considered to be more appropriate. The specificity of this intermediate structure was to immediately organize, upon discharge, outpatient services at home. The low rate of potentially avoidable readmissions, the high patient satisfaction scores, the absence of premature death and the low number of iatrogenic complications suggest that medical and nursing care delivered reflect a good quality of services. The cost was significantly lower than expected, after adjusting for case mix. CONCLUSION: The pilot experience showed that a short-stay hospitalization unit was feasible with acceptable security conditions. The attending physician's knowledge of the patients allowed this system tofocus on essential issues without proposing inappropriate services.

Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis.

Randomized, controlled trials have demonstrated efficacy for second-generation antipsychotics in the treatment of acute mania in bipolar disorder. Despite depression being considered the hallmark of bipolar disorder, there are no published systematic reviews or meta-analyses to evaluate the efficacy of modern atypical antipsychotics in bipolar depression. We systematically reviewed published or registered randomized, double-blind, placebo-controlled trials (RCTs) of modern antipsychotics in adult bipolar I and/or II depressive patients (DSM-IV criteria). Efficacy outcomes were assessed based on changes in the Montgomery-Asberg Depression Rating Scale (MADRS) during an 8-wk period. Data were combined through meta-analysis using risk ratio as an effect size with a 95% confidence interval (95% CI) and with a level of statistical significance of 5% (p<0.05). We identified five RCTs; four involved antipsychotic monotherapy and one addressed both monotherapy and combination with an antidepressant. The two quetiapine trials analysed the safety and efficacy of two doses: 300 and 600 mg/d. The only olanzapine trial assessed olanzapine monotherapy within a range of 5-20 mg/d and olanzapine-fluoxetine combination within a range of 5-20 mg/d and 6-12 mg/d, respectively. The two aripiprazole placebo-controlled trials assessed doses of 5-30 mg/d. Quetiapine and olanzapine trials (3/5, 60%) demonstrated superiority over placebo (p<0.001). Only 2/5 (40%) (both aripiprazole trials) failed in the primary efficacy measure after the first 6 wk. Some modern antipsychotics (quetiapine and olanzapine) have demonstrated efficacy in bipolar depressive patients from week 1 onwards. Rapid onset of action seems to be a common feature of atypical antipsychotics in bipolar depression. Comment in The following popper user interface control may not be accessible. Tab to the next button to revert the control to an accessible version.Destroy user interface controlEfficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis--results to be interpreted with caution.

A systematic review and meta-analysis of lithium augmentation of tricyclic and second generation antidepressants in major depression.

BACKGROUND: Lithium augmentation of antidepressants for treatment of unipolar major depression was one of the first adjunctive strategies based on a neuropharmacologic rationale. Randomized controlled trials supported its efficacy but most trials added lithium to tricyclic antidepressants (TCAs). Despite its efficacy, use of lithium augmentation remains infrequent. The current systematic review and meta-analysis examines the efficacy of lithium augmentation as an adjunct to second generation antidepressants as well as to TCAs and considers reasons for its infrequent use. METHOD: A systematic search of Medline and the Cochrane Clinical Trials database was performed. Randomized, placebo-controlled trials of lithium augmentation were selected. A fixed-effects meta-analysis was performed. Odds ratios for response were calculated for each treatment-control contrast, for the trials grouped by type of initial antidepressant (TCA or second generation antidepressant), and as a meta-analytic summary for all treatments combined. RESULTS: Nine trials that included 237 patients were selected. The odds ratio for response to lithium vs. placebo in all contrasts combined was 2.89 (95% CI 1.65, 5.05, z=3.72, p=0.0002). Heterogeneity was very low, I(2)=0%. Adjunctive lithium was effective with TCAs (7 contrasts) and with second generation agents (3 contrasts). Discontinuation due to adverse events was infrequent and did not differ between lithium and placebo. LIMITATIONS: The meta-analysis is limited by the small size and number of trials and limited data for treatment resistant patients. CONCLUSIONS: Adjunctive lithium appears to be as effective for second generation antidepressants as it was for the tricyclics.

Cost-effectiveness of a community pharmacist intervention in patients with depression: a randomized controlled trial (PRODEFAR study)

Background: Non-adherence to antidepressants generates higher costs for the treatment of depression. Little is known about the cost-effectiveness of pharmacist's interventions aimed at improving adherence to antidepressants. The study aimed to evaluate the cost-effectiveness of a community pharmacist intervention in comparison with usual care in depressed patients initiating treatment with antidepressants in primary care. Methods: Patients were recruited by general practitioners and randomized to community pharmacist intervention (87) that received an educational intervention and usual care (92). Adherence to antidepressants, clinical symptoms, Quality-Adjusted Life-Years (QALYs), use of healthcare services and productivity losses were measured at baseline, 3 and 6 months. Results: There were no significant differences between groups in costs or effects. From a societal perspective, the incremental cost-effectiveness ratio (ICER) for the community pharmacist intervention compared with usual care was 1,866 for extra adherent patient and 9,872 per extra QALY. In terms of remission of depressive symptoms, the usual care dominated the community pharmacist intervention. If willingness to pay (WTP) is 30,000 per extra adherent patient, remission of symptoms or QALYs, the probability of the community pharmacist intervention being cost-effective was 0.71, 0.46 and 0.75, respectively (societal perspective). From a healthcare perspective, the probability of the community pharmacist intervention being cost-effective in terms of adherence, QALYs and remission was of 0.71, 0.76 and 0.46, respectively, if WTP is 30,000. Conclusion: A brief community pharmacist intervention addressed to depressed patients initiating antidepressant treatment showed a probability of being cost-effective of 0.71 and 0.75 in terms of improvement of adherence and QALYs, respectively, when compared to usual care. Regular implementation of the community pharmacist intervention is not recommended.

Evaluation of a pharmacist intervention on patients initiating pharmacological treatment for depression: a randomized controlled superiority trial

Major depression is associated with high burden, disability and costs. Non-adherence limits the effectiveness of antidepressants. Community pharmacists (CP) are in a privileged position to help patients cope with antidepressant treatment. The aim of the study was to evaluate the impact of a CP intervention on primary care patients who had initiated antidepressant treatment. Newly diagnosed primary care patients were randomised to usual care (UC) (92) or pharmacist intervention (87). Patients were followed up at 6 months and evaluated three times (Baseline, and at 3 and 6 months). Outcome measurements included clinical severity of depression (PHQ-9), health-related quality of life (HRQOL) (Euroqol-5D) and satisfaction with pharmacy care. Adherence was continuously registered from the computerised pharmacy records. Non-adherence was defined as refilling less than 80% of doses or having a medication-free gap of more than 1 month. Patients in the intervention group were more likely to remain adherent at 3 and 6 months follow-up but the difference was not statistically significant. Patients in the intervention group showed greater statistically significant improvement in HRQOL compared with UC patients both in the main analysis and PP analyses. No statistically significant differences were observed in clinical symptoms or satisfaction with the pharmacy service. The results of our study indicate that a brief intervention in community pharmacies does not improve depressed patients' adherence or clinical symptoms. This intervention helped patients to improve their HRQOL, which is an overall measure of patient status.

Synaptic depression and slow oscillatory activity in a biophysical network model of the cerebral cortex

Short-term synaptic depression (STD) is a form of synaptic plasticity that has a large impact on network computations. Experimental results suggest that STD is modulated by cortical activity, decreasing with activity in the network and increasing during silent states. Here, we explored different activity-modulation protocols in a biophysical network model for which the model displayed less STD when the network was active than when it was silent, in agreement with experimental results. Furthermore, we studied how trains of synaptic potentials had lesser decay during periods of activity (UP states) than during silent periods (DOWN states), providing new experimental predictions. We next tackled the inverse question of what is the impact of modifying STD parameters on the emergent activity of the network, a question difficult to answer experimentally. We found that synaptic depression of cortical connections had a critical role to determine the regime of rhythmic cortical activity. While low STD resulted in an emergent rhythmic activity with short UP states and long DOWN states, increasing STD resulted in longer and more frequent UP states interleaved with short silent periods. A still higher synaptic depression set the network into a non-oscillatory firing regime where DOWN states no longer occurred. The speed of propagation of UP states along the network was not found to be modulated by STD during the oscillatory regime; it remained relatively stable over a range of values of STD. Overall, we found that the mutual interactions between synaptic depression and ongoing network activity are critical to determine the mechanisms that modulate cortical emergent patterns.

Influence of MCHR2 and MCHR2-AS1 Genetic Polymorphisms on Body Mass Index in Psychiatric Patients and In Population-Based Subjects with Present or Past Atypical Depression.

Obesity development during psychotropic treatments represents a major health issue in psychiatry. Melanin-concentrating hormone receptor 2 (MCHR2) is a central receptor involved in energy homeostasis. MCHR2 shares its promoter region with MCHR2-AS1, a long antisense non-coding RNA. The aim of this study was to determine whether tagging single nucleotide polymorphisms (tSNPs) of MCHR2 and MCHR2-AS1 are associated with the body mass index (BMI) in the psychiatric and in the general population. The influence of MCHR2 and MCHR2-AS1 tSNPs on BMI was firstly investigated in a discovery psychiatric sample (n1 = 474). Positive results were tested for replication in two other psychiatric samples (n2 = 164, n3 = 178) and in two population-based samples (CoLaus, n4 = 5409; GIANT, n5 = 113809). In the discovery sample, TT carriers of rs7754794C>T had 1.08 kg/m2 (p = 0.04) lower BMI as compared to C-allele carriers. This observation was replicated in an independent psychiatric sample (-2.18 kg/m2; p = 0.009). The association of rs7754794C>T and BMI seemed stronger in subjects younger than 45 years (median of age). In the population-based sample, a moderate association was observed (-0.17 kg/m2; p = 0.02) among younger individuals (<45y). Interestingly, this association was totally driven by patients meeting lifetime criteria for atypical depression, i.e. major depressive episodes characterized by symptoms such as an increased appetite. Indeed, patients with atypical depression carrying rs7754794-TT had 1.17 kg/m2 (p = 0.04) lower BMI values as compared to C-allele carriers, the effect being stronger in younger individuals (-2.50 kg/m2; p = 0.03; interaction between rs7754794 and age: p-value = 0.08). This study provides new insights on the possible influence of MCHR2 and/or MCHR2-AS1 on obesity in psychiatric patients and on the pathophysiology of atypical depression.

Frequency of and Risk Factors for Depression among Participants in the Swiss HIV Cohort Study (SHCS).

OBJECTIVES: We studied the incidence and prevalence of, and co-factors for depression in the Swiss HIV Cohort Study. METHODS: Depression-specific items were introduced in 2010 and prospectively collected at semiannual cohort visits. Clinical, laboratory and behavioral co-factors of incident depression among participants free of depression at the first two visits in 2010 or thereafter were analyzed with Poisson regression. Cumulative prevalence of depression at the last visit was analyzed with logistic regression. RESULTS: Among 4,422 participants without a history of psychiatric disorders or depression at baseline, 360 developed depression during 9,348 person-years (PY) of follow-up, resulting in an incidence rate of 3.9 per 100 PY (95% confidence interval (CI) 3.5-4.3). Cumulative prevalence of depression during follow-up was recorded for 1,937/6,756 (28.7%) participants. Incidence and cumulative prevalence were higher in injection drug users (IDU) and women. Older age, preserved work ability and higher physical activity were associated with less depression episodes. Mortality (0.96 per 100 PY, 95% CI 0.83-1.11) based upon 193 deaths over 20,102 PY was higher among male IDU (2.34, 1.78-3.09), female IDU (2.33, 1.59-3.39) and white heterosexual men (1.32, 0.94-1.84) compared to white heterosexual women and homosexual men (0.53, 0.29-0.95; and 0.71, 0.55-0.92). Compared to participants free of depression, mortality was slightly elevated among participants with a history of depression (1.17, 0.94-1.45 vs. 0.86, 0.71-1.03, P = 0.033). Suicides (n = 18) did not differ between HIV transmission groups (P = 0.50), but were more frequent among participants with a prior diagnosis of depression (0.18 per 100 PY, 95%CI 0.10-0.31; vs. 0.04, 0.02-0.10; P = 0.003). CONCLUSIONS: Depression is a frequent co-morbidity among HIV-infected persons, and thus an important focus of care.

Relationship between obesity and the risk of clinically significant depression: Mendelian randomisation study.

BACKGROUND: Obesity has been shown to be associated with depression and it has been suggested that higher body mass index (BMI) increases the risk of depression and other common mental disorders. However, the causal relationship remains unclear and Mendelian randomisation, a form of instrumental variable analysis, has recently been employed to attempt to resolve this issue. AIMS: To investigate whether higher BMI increases the risk of major depression. METHOD: Two instrumental variable analyses were conducted to test the causal relationship between obesity and major depression in RADIANT, a large case-control study of major depression. We used a single nucleotide polymorphism (SNP) in FTO and a genetic risk score (GRS) based on 32 SNPs with well-established associations with BMI. RESULTS: Linear regression analysis, as expected, showed that individuals carrying more risk alleles of FTO or having higher score of GRS had a higher BMI. Probit regression suggested that higher BMI is associated with increased risk of major depression. However, our two instrumental variable analyses did not support a causal relationship between higher BMI and major depression (FTO genotype: coefficient -0.03, 95% CI -0.18 to 0.13, P = 0.73; GRS: coefficient -0.02, 95% CI -0.11 to 0.07, P = 0.62). CONCLUSIONS: Our instrumental variable analyses did not support a causal relationship between higher BMI and major depression. The positive associations of higher BMI with major depression in probit regression analyses might be explained by reverse causality and/or residual confounding.

Clinical and course characteristics of depression and all-cause mortality: A prospective population-based study.

BACKGROUND: Given the large heterogeneity of depressive disorders (DD), studying depression characteristics according to clinical manifestations and course is a more promising approach than studying depression as a whole. The purpose of this study was to determine the association between clinical and course characteristics of DD and incident all-cause mortality. METHODS: CoLaus|PsyCoLaus is a prospective cohort study (mean follow-up duration=5.2 years) including 35-66 year-old randomly selected residents of an urban area in Switzerland. A total of 3668 subjects (mean age 50.9 years, 53.0% women) underwent physical and psychiatric baseline evaluations and had a known vital status at follow-up (98.8% of the baseline sample). Clinical (diagnostic severity, atypical features) and course characteristics (recency, recurrence, duration, onset) of DD according to the DSM-5 were elicited using a semi-structured interview. RESULTS: Compared to participants who had never experienced DD, participants with current but not remitted DD were more than three times as likely to die (Hazard Ratio: 3.2, 95% CI: 1.1-10.0) after adjustment for socio-demographic and lifestyle characteristics, comorbid anxiety disorders, antidepressant use, and cardiovascular risk factors and diseases. There was no evidence for associations between other depression characteristics and all-cause mortality. LIMITATIONS: The small proportion of deceased subjects impeded statistical analyses of cause-specific mortality. CONCLUSIONS: A current but not remitted DD is a strong predictor of all-cause mortality, independently of cardiovascular or lifestyle factors, which suggests that the effect of depression on mortality diminishes after remission and further emphasizes the need to adequately treat current depressive episodes.

Tracing the associations between sex, the atypical and the combined atypical-melancholic depression subtypes: A path analysis.

BACKGROUND: Numerous studies have examined determinants leading to preponderance of women in major depressive disorder (MDD), which is particularly accentuated for the atypical depression subtype. It is thus of interest to explore the specific indirect effects influencing the association between sex and established depression subtypes. METHODS: The data of 1624 subjects with a lifetime diagnosis of MDD derived from the population-based PsyCoLaus data were used. An atypical (n=256), a melancholic (n=422), a combined atypical and melancholic features subtype (n=198), and an unspecified MDD group (n=748) were constructed according to the DSM-IV specifiers. Path models with direct and indirect effects were applied to the data. RESULTS: Partial mediation of the female-related atypical and combined atypical-melancholic depression subtypes was found. Early anxiety disorders and high emotion-orientated coping acted as mediating variables between sex and the atypical depression subtype. In contrast, high Body Mass Index (BMI) served as a suppression variable, also concerning the association between sex and the combined atypical-melancholic subtype. The latter association was additionally mediated by an early age of MDD onset and early/late anxiety disorders. LIMITATIONS: The use of cross-sectional data does not allow causal conclusions. CONCLUSIONS: This is the first study that provides evidence for a differentiation of the general mechanisms explaining sex differences of overall MDD by depression subtypes. Determinants affecting the pathways begin early in life. Since some of them are primarily of behavioral nature, the present findings could be a valuable target in mental health care.