Treatment of Depression in Older Adults

Depression is the most frequent mental disorder in older people, often causing emotional distress and reduced quality of life. Despite its clinical significance, depression remains underdiagnosed and inadequately treated in older patients. Regarding prognosis, data suggest that almost 70% of patients, treated long enough and with appropriate doses, recover from an index episode of depression. Antidepressants are efficient for treating depressed outpatients with several comorbid physical diseases as well as hospitalized patients, with selective serotonin reuptake inhibitors being the antidepressants of choice for older patients. Available data can guide pharmacological treatment in both the acute and maintenance stages, but further research is required to guide clinical strategies when remission is not achieved. Approaches for the management of resistance to treatment are summarized, including optimization strategies, drug changes, algorithms, and combined and augmentation pharmacological treatments. Finally, additional therapeutic choices such as electroconvulsive therapy, transcranial magnetic stimulation, and integrated psychotherapy are presented.

The ARIQUELI study: potentiation of quetiapine in bipolar I nonresponders with lithium versus aripiprazole

Abstract Background:The treatment of bipolar disorder (BD) remains a challenge due to the complexity of the disease. Current guidelines represent an effort to assist clinicians in routine practice but have several limitations, particularly concerning long-term treatment. The ARIQUELI (efficacy and tolerability of the combination of lithium or aripiprazole in young bipolar non or partial responders to quetiapine monotherapy) study aims to evaluate two different augmentation strategies for quetiapine nonresponders or partial responders in acute and maintenance phases of BD treatment. Methods/Design: The ARIQUELI study is a single-site, parallel-group, randomized, outcome assessor-blinded trial. BD I patients according to the DSM-IV-TR, in depressive, manic/hypomanic or mixed episode, aged 18 to 40 years, are eligible. After diagnostic assessments, patients initiated treatment in phase I with quetiapine. Nonresponders or partial responders after 8 weeks are allocated into one of two groups, potentiated with either lithium (0.5 to 0.8 mEq/l) or aripiprazole (10 or 15 mg). Patients will be followed up for 8 weeks in phase I (acute treatment), 6 months in phase II (continuation treatment) and 12 months in phase III (maintenance treatment). Outcome assessors are blinded to the treatment. The primary outcome is the evaluation of changes in mean scores on the CGI-BP-M between baseline and the endpoint at the end of each study phase. Discussion: The ARIQUELI study is currently in progress, with patients undergoing acute treatment (phase I), potentiation (phase II) and maintenance (phase III). The study will be extended until January 2015. Trials comparing lithium and aripiprazole with potentiate treatment in young BD I nonresponders to quetiapine in monotherapy can provide relevant information on the safety of these drugs in clinical practice. Long-term treatment is an issue of great importance and should be evaluated further through more in-depth studies given that BD is a chronic disease. Trial registration: ClinicalTrials.gov identifier: NCT01710163

Treatment of adolescents with early-onset schizophrenia spectrum disorders: in search of a rational, evidence-informed approach

Purpose of review: We aimed to review literature on the efficacy and tolerability of psychosocial and psychopharmacological interventions in youth with early-onset schizophrenia spectrum disorders (EOS). A rationale for pragmatic psychopharmacology in EOS, including dosing, switching and adverse effect monitoring and management, is provided. Recent findings: Three randomized controlled trials (RCTs) over the last 8 years demonstrated benefits of psychosocial interventions (i.e. psychoeducation, cognitive remediation, cognitive behavioural therapy) for EOS without clear advantages of one psychosocial treatment over another. Six large, placebo-controlled, short-term RCTs over the last 4 years demonstrated that aripiprazole, olanzapine, paliperidone, quetiapine and risperidone, but not ziprasidone, were superior to placebo. Except for clozapine's superiority in treatment-refractory EOS, efficacy appeared similar across studied first-generation and second-generation antipsychotics, but tolerability varied greatly across individual agents. Summary: Antipsychotics are efficacious in the treatment of EOS. Given the lack of efficacy differences between antipsychotics (except for clozapine for treatment-refractory EOS), we propose that tolerability considerations need to guide choice of antipsychotics. Further and longer-term efficacy and effectiveness studies are urgently needed that should also explore pharmacologic and nonpharmacologic augmentation strategies.

Glutathione in Parkinson's disease

Thesis (Ph.D.)--University of Washington, 2016-03

Adjunctive nutraceuticals for depression: a systematic review and meta-analyses

OBJECTIVE: There is burgeoning interest in augmentation strategies for improving inadequate response to antidepressants. The adjunctive use of standardized pharmaceutical-grade nutrients, known as nutraceuticals, has the potential to modulate several neurochemical pathways implicated in depression. While many studies have been conducted in this area, to date no specialized systematic review (or meta-analysis) has been conducted. METHOD: A systematic search of PubMed, CINAHL, Cochrane Library, and Web of Science was conducted up to December 2015 for clinical trials using adjunctive nutrients for depression. Where sufficient data were available, a random-effects model analyzed the standard mean difference between treatment and placebo in the change from baseline to endpoint, combining the effect size data. Funnel plot and heterogeneity analyses were also performed. RESULTS: Primarily positive results were found for replicated studies testing S-adenosylmethionine (SAMe), methylfolate, omega-3 (primarily EPA or ethyl-EPA), and vitamin D, with positive isolated studies for creatine, folinic acid, and an amino acid combination. Mixed results were found for zinc, folic acid, vitamin C, and tryptophan, with nonsignificant results for inositol. No major adverse effects were noted in the studies (aside from minor digestive disturbance). A meta-analysis of adjunctive omega-3 versus placebo revealed a significant and moderate to strong effect in favor of omega-3. Conversely, a meta-analysis of folic acid revealed a nonsignificant difference from placebo. Marked study heterogeneity was found in a Higgins test for both omega-3 and folic acid studies; funnel plots also revealed asymmetry (reflecting potential study bias). CONCLUSIONS: Current evidence supports adjunctive use of SAMe, methylfolate, omega-3, and vitamin D with antidepressants to reduce depressive symptoms.

Selecting Robust Strategies in RTS Games via Concurrent Plan Augmentation

Thesis (Master's)--University of Washington, 2015

Experimental and Numerical Studies in a Compact Trapped Vortex Combustor: Stability Assessment and Augmentation

Fundamental studies on a compact trapped vortex combustor indicate that cavity injection strategies play a major role on flame stability. Detailed experiments indicate that blow-out occurs for a certain range of cavity air flow velocities. An unsteady RANS-based reacting flow simulation tool has been utilized to study the basic dynamics of cavity vortex for various flow conditions. The phenomenon of flame blow-out at certain intermediate cavity air velocities is explained on the basis of transition from a cavity-stabilized mode to an opposed flow stagnation mode. A novel strategy is proposed for achieving flame stability at all conditions. This involves using a flow guide vane in the path of the main flow to direct a portion of the main flow into the cavity. This seems to result in a desirable dual vortex structure, i.e., a small clockwise vortex behind the vane and large counterclockwise vortex in the cavity. Experimental results show stable flame at all flow conditions with the flow guide vane, and pressure drop is estimated to be within acceptable limits. Cold flow simulations show self-similar velocity profiles for a range of main inlet velocities, and high reverse velocity ratios (-0.3) are observed. Such a high-velocity ratio in the reverse flow shear layer profile leads to enhanced production of turbulence imperative to compact combustors. Reacting flow simulations show even higher reverse velocity ratios (above -0.7) due to flow acceleration. The flame is observed to be stable, even though minor shear layer oscillations are present in the form of vortex shedding. Self-similarity is also observed in reacting flow temperature profiles at combustor exit over the entire range of the mainstream velocity. This indicates that the present configuration holds a promise of delivering robust performance invariant of the flow operating conditions.

Torrenting values, feelings and thoughts : cyber nursing and virtual self care in a breast augmentation forum

Earlier research shows that breast augmentation is positively correlated with positive psychological states. The aim of this study was to explore the shared values, feelings, and thoughts within the culture of breast enlargement among women visiting Internet-based forums when considering and/or undergoing esthetic plastic surgery. The study used a netnographic method for gathering and analyzing data. The findings show that the women used the Internet forum to provide emotional support to other women. Through electronic postings, they cared for and nursed each others’ anxiety and feelings throughout the whole process. Apart from the process, another central issue was that the women's relationships were frequently discussed; specifically their relationship to themselves, their environment, and with the surgeons. The findings suggest that Internet forums represent a channel through which posters can share values, feelings, and thoughts from the position of an agent of action as well as from a position as the object of action. These dual positions and the medium endow the women with a virtual nursing competence that would otherwise be unavailable. By introducing the concept of torrenting as a means of sharing important self-care information, the authors provide a concept that can be further explored in relation to post modern self-care strategies within contemporary nursing theories and practice.

Youth Depression Alleviation-Augmentation with an anti-inflammatory agent (YoDA-A): protocol and rationale for a placebo-controlled randomized trial of rosuvastatin and aspirin

AIM: There is growing support for the role of inflammation and oxidative stress in the pathophysiology of major depressive disorder (MDD). This has led to the development of novel strategies targeting inflammation in the treatment of depression. Rosuvastatin and aspirin have well-documented, anti-inflammatory and antioxidant properties. The aim of the Youth Depression Alleviation: Augmentation with an anti-inflammatory agent (YoDA-A) study is to determine whether individuals receiving adjunctive anti-inflammatory agents, aspirin and rosuvastatin experience a reduction in the severity of MDD compared with individuals receiving placebo. METHODS: YoDA-A is a 12-week triple-blind, randomized controlled trial funded by the National Health and Medical Research Council, Australia. Participants aged 15-25, with moderate-to-severe MDD, are allocated to receive either 10 mg/day rosuvastatin, 100 mg/day aspirin, or placebo, in addition to treatment as usual. Participants are assessed at baseline and at weeks 4, 8, 12 and 26. The primary outcome is change in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to week 12. RESULTS: The study is planned to be completed in 2017. At date of publication, 85 participants have been recruited. CONCLUSION: Timely and targeted intervention for youth MDD is crucial. Given the paucity of new agents to treat youth MDD, adjunctive trials are not only pragmatic and 'real-world', but additionally aim to target shortfalls in conventional medications. This study has the potential to first provide two new adjunctive treatment options for youth MDD; aspirin and rosuvastatin. Second, this study will serve as proof of principle of the role of inflammation in MDD.

Biologically based strategies to augment rotator cuff tears

Lesions of the rotator cuff (RC) are among the most frequent tendon injuries. In spite of the developments in both open and arthroscopic surgery, RC repair still very often fails. In order to reduce the failure rate after surgery, several experimental in vitro and in vivo therapy methods have been developed for biological improvement of the reinsertion. This article provides an overview of the current evidence for augmentation of RC reconstruction with growth factors. Furthermore, potential future therapeutic approaches are discussed. We performed a comprehensive search of the PubMed database using various combinations of the keywords "tendon," "rotator cuff," "augmentation," "growth factor," "platelet-rich fibrin," and "platelet-rich plasma" for publications up to 2011. Given the linguistic capabilities of the research team, we considered publications in English, German, French, and Spanish. We excluded literature reviews, case reports, and letters to the editor.

Development of mathematical models to elaborate strategies, select alternatives and development of plans for adaptation of communities to climate change in different geographical areas including costs to implement it.

There is evidence that the climate changes and that now, the change is influenced and accelerated by the CO2 augmentation in atmosphere due to combustion by humans. Such ?Climate change? is on the policy agenda at the global level, with the aim of understanding and reducing its causes and to mitigate its consequences. In most countries and international organisms UNO (e.g. Rio de Janeiro 1992), OECD, EC, etc . . . the efforts and debates have been directed to know the possible causes, to predict the future evolution of some variable conditioners, and trying to make studies to fight against the effects or to delay the negative evolution of such. The Protocol of Kyoto 1997 set international efforts about CO2 emissions, but it was partial and not followed e.g. by USA and China . . . , and in Durban 2011 the ineffectiveness of humanity on such global real challenges was set as evident. Among all that, the elaboration of a global model was not boarded that can help to choose the best alternative between the feasible ones, to elaborate the strategies and to evaluate the costs, and the authors propose to enter in that frame for study. As in all natural, technological and social changes, the best-prepared countries will have the best bear and the more rapid recover. In all the geographic areas the alternative will not be the same one, but the model must help us to make the appropriated decision. It is essential to know those areas that are more sensitive to the negative effects of climate change, the parameters to take into account for its evaluation, and comprehensive plans to deal with it. The objective of this paper is to elaborate a mathematical model support of decisions, which will allow to develop and to evaluate alternatives of adaptation to the climatic change of different communities in Europe and Latin-America, mainly in especially vulnerable areas to the climatic change, considering in them all the intervening factors. The models will consider criteria of physical type (meteorological, edaphic, water resources), of use of the ground (agriculturist, forest, mining, industrial, urban, tourist, cattle dealer), economic (income, costs, benefits, infrastructures), social (population), politician (implementation, legislation), educative (Educational programs, diffusion) and environmental, at the present moment and the future. The intention is to obtain tools for aiding to get a realistic position for these challenges, which are an important part of the future problems of humanity in next decades.

Augmentation de l'immunogénicité de la nucléoprotéine de l'influenza par multimérisation in vitro

Les travaux effectués au cours de ce mémoire ont permis de développer une alternative aux vaccins présentement utilisés contre le virus de l’influenza. Nous avons utilisé la nucléoprotéine (NP) de l’influenza comme base vaccinale puisque cette protéine est conservée chez les souches d’influenza A et qu’elle possède un potentiel de protection croisée. Nous avons montré que la multimérisation de la NP grâce à un gabarit d’ARN permet d’augmenter son immunogenicité. Cette multimérisation en pseudo-nucléoparticule virale (NLP) a augmenté la réponse humorale et cellulaire spécifique à NP et l’ajout d’un adjuvant (PAL) a permis d’amplifier davantage la réponse humorale contre NP. Une dose du vaccin candidat NLP-PAL n’a pas réussi à protéger des souris contre une infection létale avec une souche homotypique d’influenza. Cependant, des résultats avec un régime de deux immunisations montrent des résultats encourageants qui permettent d’espérer une protection envers une infection virale.