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As depression has a recurrent course, relapse and recurrence prevention is essential.
In our randomised controlled trial (registered with the Nederlands trial register, identifier: NTR1907), we found that adding preventive cognitive therapy (PCT) to maintenance antidepressants (PCT+AD) yielded substantial protective effects versus antidepressants only in individuals with recurrent depression. Antidepressants were not superior to PCT while tapering antidepressants (PCT/−AD). To inform decision-makers on treatment allocation, we present the corresponding cost-effectiveness, cost-utility and budget impact.
Data were analysed (n = 289) using a societal perspective with 24-months of follow-up, with depression-free days and quality-adjusted life years (QALYs) as health outcomes. Incremental cost-effectiveness ratios were calculated and cost-effectiveness planes and cost-effectiveness acceptability curves were derived to provide information about cost-effectiveness. The budget impact was examined with a health economic simulation model.
Mean total costs over 24 months were €6814, €10 264 and €13 282 for AD+PCT, antidepressants only and PCT/−AD, respectively. Compared with antidepressants only, PCT+AD resulted in significant improvements in depression-free days but not QALYs. Health gains did not significantly favour antidepressants only versus PCT/−AD. High probabilities were found that PCT+AD versus antidepressants only and antidepressants only versus PCT/−AD were dominant with low willingness-to-pay thresholds. The budget impact analysis showed decreased societal costs for PCT+AD versus antidepressants only and for antidepressants only versus PCT/−AD.
Adding PCT to antidepressants is cost-effective over 24 months and PCT with guided tapering of antidepressants in long-term users might result in extra costs. Future studies examining costs and effects of antidepressants versus psychological interventions over a longer period may identify a break-even point where PCT/−AD will become cost-effective.
Declaration of interest
C.L.H.B. is co-editor of PLOS One and receives no honorarium for this role. She is also co-developer of the Dutch multidisciplinary clinical guideline for anxiety and depression, for which she receives no remuneration. She is a member of the scientific advisory board of the National Insure Institute, for which she receives an honorarium, although this role has no direct relation to this study. C.L.H.B. has presented keynote addresses at conferences, such as the European Psychiatry Association and the European Conference Association, for which she sometimes receives an honorarium. She has presented clinical training workshops, some including a fee. She receives royalties from her books and co-edited books and she developed preventive cognitive therapy on the basis of the cognitive model of A. T. Beck. W.A.N. has received grants from the Netherlands Organisation for Health Research and Development and the European Union and honoraria and speakers' fees from Lundbeck and Aristo Pharma, and has served as a consultant for Daleco Pharma.
Major depressive disorder (MDD) is a highly heterogeneous condition in terms of symptom presentation and, likely, underlying pathophysiology. Accordingly, it is possible that only certain individuals with MDD are well-suited to antidepressants. A potentially fruitful approach to parsing this heterogeneity is to focus on promising endophenotypes of depression, such as neuroticism, anhedonia, and cognitive control deficits.
Within an 8-week multisite trial of sertraline v. placebo for depressed adults (n = 216), we examined whether the combination of machine learning with a Personalized Advantage Index (PAI) can generate individualized treatment recommendations on the basis of endophenotype profiles coupled with clinical and demographic characteristics.
Five pre-treatment variables moderated treatment response. Higher depression severity and neuroticism, older age, less impairment in cognitive control, and being employed were each associated with better outcomes to sertraline than placebo. Across 1000 iterations of a 10-fold cross-validation, the PAI model predicted that 31% of the sample would exhibit a clinically meaningful advantage [post-treatment Hamilton Rating Scale for Depression (HRSD) difference ⩾3] with sertraline relative to placebo. Although there were no overall outcome differences between treatment groups (d = 0.15), those identified as optimally suited to sertraline at pre-treatment had better week 8 HRSD scores if randomized to sertraline (10.7) than placebo (14.7) (d = 0.58).
A subset of MDD patients optimally suited to sertraline can be identified on the basis of pre-treatment characteristics. This model must be tested prospectively before it can be used to inform treatment selection. However, findings demonstrate the potential to improve individual outcomes through algorithm-guided treatment recommendations.
Depression and obesity are highly prevalent, and major impacts on public health frequently co-occur. Recently, we reported that having depression moderates the effect of the FTO gene, suggesting its implication in the association between depression and obesity.
To confirm these findings by investigating the FTO polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis.
The sample consists of 6902 individuals with depression and 6799 controls from three replication cohorts and two original discovery cohorts. Linear regression models were performed to test for association between rs9939609 and body mass index (BMI), and for the interaction between rs9939609 and depression status for an effect on BMI. Fixed and random effects meta-analyses were performed using METASOFT.
In the replication cohorts, we observed a significant interaction between FTO, BMI and depression with fixed effects meta-analysis (β=0.12, P = 2.7 × 10−4) and with the Han/Eskin random effects method (P = 1.4 × 10−7) but not with traditional random effects (β = 0.1, P = 0.35). When combined with the discovery cohorts, random effects meta-analysis also supports the interaction (β = 0.12, P = 0.027) being highly significant based on the Han/Eskin model (P = 6.9 × 10−8). On average, carriers of the risk allele who have depression have a 2.2% higher BMI for each risk allele, over and above the main effect of FTO.
This meta-analysis provides additional support for a significant interaction between FTO, depression and BMI, indicating that depression increases the effect of FTO on BMI. The findings provide a useful starting point in understanding the biological mechanism involved in the association between obesity and depression.
Objectives: The aim of this study was to demonstrate the utility of an evidence-based assessment (EBA) model to establish a multimodal set of tools for identifying students at risk for perceived post-injury academic problems. Methods: Participants included 142 students diagnosed with concussion (age: M=14.95; SD=1.80; 59% male), evaluated within 4 weeks of injury (median=16 days). Demographics, pre-injury history, self- and parent-report measures assessing symptom severity and executive functions, and cognitive test performance were examined as predictors of self-reported post-injury academic problems. Results: Latent class analysis categorized participants into “high” (44%) and “low” (56%) levels of self-reported academic problems. Receiver operating characteristic analyses revealed significant discriminative validity for self- and parent-reported symptom severity and executive dysfunction and self-reported exertional response for identifying students reporting low versus high academic problems. Parent-reported symptom ratings [area under the receiver operating characteristic curve (AUC)=.79] and executive dysfunction (AUC=.74), and self-reported ratings of executive dysfunction (AUC=.84), symptoms (AUC=.80), and exertional response (AUC=.70) each classified students significantly better than chance (ps<.001). Hierarchical logistic regression indicated that, of the above, self-reported symptoms and executive dysfunction accounted for the most variance in the prediction of self-reported academic problems. Conclusions: Post-concussion symptom severity and executive dysfunction significantly predict perceived post-injury academic problems. EBA modeling identified the strongest set of predictors of academic challenges, offering an important perspective in the management of concussion by applying traditional strengths of neuropsychological assessment to clinical decision making. (JINS, 2016, 22, 1038–1049)
A previous study showed the additive methane (CH4)-mitigating effect of nitrate and linseed fed to non-lactating cows. Before practical application, the use of this new strategy in dairy cows requires further investigation in terms of persistency of methanogenesis reduction and absence of residuals in milk products. The objective of this experiment was to study the long-term effect of linseed plus nitrate on enteric CH4 emission and performance in dairy cows. We also assessed the effect of this feeding strategy on the presence of nitrate residuals in milk products, total tract digestibility, nitrogen (N) balance and rumen fermentation. A total of 16 lactating Holstein cows were allocated to two groups in a randomised design conducted in parallel for 17 weeks. Diets were on a dry matter (DM) basis: (1) control (54% maize silage, 6% hay and 40% concentrate; CON) or (2) control plus 3.5% added fat from linseed and 1.8% nitrate (LIN+NIT). Diets were equivalent in terms of CP (16%), starch (28%) and NDF (33%), and were offered twice daily. Cows were fed ad libitum, except during weeks 5, 16 and 17 in which feed was restricted to 95% of dry matter intake (DMI) to ensure complete consumption of meals during measurement periods. Milk production and DMI were measured weekly. Nitrate and nitrite concentrations in milk and milk products were determined monthly. Daily CH4 emission was quantified in open circuit respiration chambers (weeks 5 and 16). Total tract apparent digestibility, N balance and rumen fermentation parameters were determined in week 17. Daily DMI tended to be lower with LIN+NIT from week 4 to 16 (−5.1 kg/day on average). The LIN+NIT diet decreased milk production during 6 non-consecutive weeks (−2.5 kg/day on average). Nitrate or nitrite residuals were not detected in milk and associated products. The LIN+NIT diet reduced CH4 emission to a similar extent at the beginning and end of the trial (−47%, g/day; −30%, g/kg DMI; −33%, g/kg fat- and protein-corrected milk, on average). Diets did not affect N efficiency and nutrients digestibility. In the rumen, LIN+NIT did not affect protozoa number but reduced total volatile fatty acid (−12%) and propionate (−31%) concentrations. We concluded that linseed plus nitrate may have a long-term CH4-mitigating effect in dairy cows and that consuming milk products from cows fed nitrate may be safe in terms of nitrate and nitrite residuals. Further work is required to optimise the doses of linseed plus nitrate to avoid reduced cows performance.
Increased intake of vegetable oils rich in n-6 PUFA, including soyabean oil, has been associated with an increase in allergic disease. The present study aimed to determine the effect of an increasing dose of dietary vegetable oil on allergic outcomes in mice. To study this, mice received a 7 v. 10 % soyabean oil diet before and during oral sensitisation with whey or whey hyperimmune serum transfer. Another group of mice received partial whey hydrolysate (pWH) while being fed the diets before oral sensitisation. The acute allergic skin response, serum Ig level, mouse mast cell protease-1 (mMCP-1) concentration and/or splenic T-cell percentages were determined upon whey challenge. When the diets were provided before and during oral sensitisation, the acute allergic skin response was increased in mice fed the 10 % soyabean oil diet compared with the 7 % soyabean oil diet. Whey IgE and IgG1 levels remained unaltered, whereas mMCP-1 levels increased in mice fed the 10 % soyabean oil diet. Furthermore, allergic symptoms were increased in naive mice fed the 10 % soyabean oil diet and sensitised with whey hyperimmune serum. In addition to enhancing the mast cell response, the 10 % soyabean oil diet increased the percentage of activated Th1 and Th2 cells as well as increased the ratios of Th2:regulatory T cells and Th2:Th1 when compared with the 7 % soyabean oil diet. Oral tolerance induction by pWH was abrogated in mice fed the 10 % soyabean oil diet compared with those fed the 7 % soyabean oil diet during pretreatment with pWH. In conclusion, increased intake of soyabean oil rich in n-6 PUFA suppresses tolerance induction by pWH and enhances the severity of the allergic effector response in whey-allergic mice. Dietary vegetable oils rich in n-6 PUFA may enhance the susceptibility to develop or sustain food allergy.
Parkinson's disease (PD) is a neurodegenerative disorder characterised by the progressive loss of midbrain dopaminergic neurons, which causes motor impairments. Current treatments involve dopamine replacement to address the disease symptoms rather than its cause. Factors that promote the survival of dopaminergic neurons have been proposed as novel therapies for PD. Several dopaminergic neurotrophic factors (NTFs) have been examined for their ability to protect and/or restore degenerating dopaminergic neurons, both in animal models and in clinical trials. These include glial cell line-derived neurotrophic factor, neurturin, cerebral dopamine neurotrophic factor and growth/differentiation factor 5. Delivery of these NTFs via injection or infusion to the brain raises several practical problems. A new delivery approach for NTFs involves the use of recombinant viral vectors to enable long-term expression of these factors in brain cells. Vectors used include those based on adenoviruses, adeno-associated viruses and lentiviruses. Here we review progress to date on the potential of each of these four NTFs as novel therapeutic strategies for PD, as well as the challenges that have arisen, from pre-clinical analysis to clinical trials. We conclude by discussing recently-developed approaches to optimise the delivery of NTF-carrying viral vectors to the brain.
Habitat loss, the primary driver for loss of biodiversity worldwide, is of special concern for species that have a small area of occurrence, such as those restricted to islands. The Forest Thrush Turdus lherminieri is a ‘Vulnerable’ (VU) species endemic to four islands in the Caribbean, and its population has declined dramatically over the past 15 years. Because this decline is poorly understood, we studied its habitat associations on Montserrat. We conducted three repeat point count surveys and measured forest structure and habitat at each of 88 randomly placed locations in the largest forest area remaining on the island. We related Forest Thrush abundance to habitat using binomial mixture models that account for imperfect detection. Detection probability was a function of survey time, survey date, location of the survey point, and wind. Local habitat structure had the greatest influence on Forest Thrush abundance, with birds being more abundant at mid-elevations under closed canopies. We conclude that the Forest Thrush prefers mature mesic and wet forests on Montserrat. Assuming similar habitat selection in the rest of its range, the species’s long-term future depends on good protection of these natural forests on all four islands where it occurs.
The UVMag consortium proposed the space mission project Arago to ESA at its M4 call. Arago is dedicated to the study of the dynamic 3D environment of stars and planets. This space mission will be equipped with a high-resolution spectropolarimeter working from 119 to 888 nm. A preliminary optical design of the whole instrument has been prepared and is presented here. The design consists of the telescope, the instrument itself, and the focusing optics. Considering not only the scientific requirements, but also the cost and size constraints to fit an M-size mission, the telescope has a 1.3 m diameter primary mirror and is a classical Cassegrain-type telescope that allows a polarization-free focus. The polarimeter is placed at this Cassegrain focus. This is the key element of the mission and the most challenging one to be designed. The main challenge lies in the huge spectral range offered by the instrument; the polarimeter has to deliver the full Stokes vector with a high precision from the FUV (119 nm) to the NIR (888 nm). The polarimeter module is then followed by a high-resolution echelle-spectrometer achieving a resolution of 35000 in the visible range and 25000 in the UV. The two channels are separated after the echelle grating, allowing specific cross-dispersion and focusing optics for the UV and the visible ranges. Considering the large field of view and the high numerical aperture, the focusing optics for both the UV and the visible channels is a Three-Mirror-Anastigmatic (TMA) telescope, needed to focus the various wavelengths and many orders onto the detectors.
Les traitements utilisant des rayons X de basse énergie continuent à être réalisés mais
en faible nombre. Le praticien se trouve en général près du patient pour maintenir
l’appareil et expose donc ses yeux. Avec la modification envisagée de la limite maximale
d’exposition du cristallin, des mesures ont été jugées nécessaires pour mieux en connaître
l’exposition. Pour cela une simulation des traitements a été réalisée. Pour la dose d’un
traitement superficiel de 42 Gy, l’exposition du cristallin derrière des verres radio
atténuateurs se situe entre 130 et 43 μSv pour des distances entre 40 et 60 cm. Pour
l’intra cavitaire les valeurs obtenues sont vingt fois plus faibles. L’atténuation par les
verres est supérieure à 90 %. Le port des lunettes avec verres radio atténuateurs permet
de minimiser la dose au cristallin de façon significative. L’application de la nouvelle
limite maximale n’aura pas d’impact sur le nombre de traitements.
Surveillance of hospital-acquired infections can be approximated by repeated surveys that are performed in a standardized, cost-effective manner. We developed an integrated software system for serial electronic hospital-wide point prevalence surveys using algorithms that proved highly sensitive and specific over a 5-year period in a large university medical center.
Declines in financial capacity in later life may arise from both neurocognitive and/or psychiatric disorders. The influence of socio-demographic, cognitive, health, and psychiatric variables on financial capacity performance was explored.
Seventy-six healthy community-dwelling adults and 25 older patients referred for assessment of financial capacity were assessed on pertinent cognitive, psychiatric, and financial capacity measures, including Addenbrooke's Cognitive Examination – Revised (ACE-R), Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), Geriatric Depression Scale (GDS), Geriatric Anxiety Inventory (GAI), selected Neuropsychiatric Inventory (NPI) items, Financial Competence Assessment Inventory (FCAI), and Social Vulnerability Scale (SVS).
The internal consistency of the debt management subscale of the FCAI was relatively poor in our sample. Financial capacity performance differed between controls and patients. In our sample, performance on the FCAI was predicted by Mini-Mental State Examination, IQCODE, and GAI, but not by ACE-R, GDS, NPI items, or SVS (adjusted R2 = 0.7059).
Anxiety but not depression predicted financial capacity performance, possibly reflecting relatively low variance of depressive symptoms in this sample. Current cognitive decline as measured by the informant-rated IQCODE was more highly correlated to financial capacity than either educational attainment or ACE-R scores. Lack of significance of ACE-R data may reflect the instrument's decreased sensitivity to domains relevant to financial capacity, compared with more detailed neuropsychological assessment tools. The FCAI displayed fairly robust psychometric properties apart from the debt management subscale.
Un cas exceptionnel de radiothérapie peropératoire intracardiaque a nécessité l’organisation de ce traitement administrativement, mais aussi en terme de radioprotection. En effet, le traitement devait être effectué dans un établissement non prévu pour des irradiations. Nous avons donc dû préparer, informer, simuler avant la réalisation. Avec l’énergie des photons de 50 kVp et les précautions prises il n’y a eu aucune incidence sur le personnel et l’environnement. Ce cas montre qu’il est possible d’envisager une externalisation de la radiothérapie peropératoire sous réserve des procédures d’autorisation et des mesures de radioprotection.
Impulsivity and compulsivity represent useful conceptualizations that involve dissociable cognitive functions, which are mediated by neuroanatomically and neurochemically distinct components of cortico-subcortical circuitry. The constructs were historically viewed as diametrically opposed, with impulsivity being associated with risk-seeking and compulsivity with harm-avoidance. However, they are increasingly recognized to be linked by shared neuropsychological mechanisms involving dysfunctional inhibition of thoughts and behaviors. In this article, we selectively review new developments in the investigation of the neurocognition of impulsivity and compulsivity in humans, in order to advance our understanding of the pathophysiology of impulsive, compulsive, and addictive disorders and indicate new directions for research.