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991.
Jonathan Messika David Hajage Nataly Panneckoucke Serge Villard Yolaine Martin Emilie Renard Annie Blivet Jean Reignier Natacha Maquigneau Annabelle Stoclin Christelle Puechberty Stéphane Guétin Aline Dechanet Amandine Fauquembergue Stéphane Gaudry Didier Dreyfuss Jean-Damien Ricard 《Trials》2016,17(1)
BackgroundNon-invasive ventilation (NIV) tolerance is a key factor of NIV success. Hence, numerous sedative pharmacological or non-pharmacological strategies have been assessed to improve NIV tolerance. Music therapy in various health care settings has shown beneficial effects. In invasively ventilated critical care patients, encouraging results of music therapy on physiological parameters, anxiety, and agitation have been reported. We hypothesize that a musical intervention improves NIV tolerance in comparison to conventional care. We therefore question the potential benefit of a receptive music session administered to patients by trained caregivers (“musical intervention”) to enhance acceptance and tolerance of NIV.Methods/designWe conduct a prospective, three-center, open-label, three-arm randomized trial involving patients in the intensive care unit (ICU) who require NIV, as assessed by the treating physician. Participants are allocated to a “musical intervention” arm (“musical intervention” applied during all NIV sessions), to a “sensory deprivation” arm (sight and hearing isolation during all NIV sessions), or to the control group. The primary endpoint is the change in respiratory comfort (measured with a digital visual scale) before the initiation and after 30 minutes of the first NIV session. The evaluation of the primary endpoint is performed blindly from the treatment group. Secondary endpoints include changes in respiratory and cardiovascular parameters during NIV sessions, the percentage of patients requiring endotracheal intubation, day-90 anxiety/depression and health-related quality of life, post-trauma stress induced by NIV, and the overall assessment of NIV.The follow-up for each participant is 90 days. We expect to randomize a total of 99 participants.DiscussionAs music intervention is a simple and easy-to-implement non-pharmacological technique, efficacious in reducing anxiety in critically ill patients, it appeared logical to assess its efficacy in NIV, one of the most stressful techniques used in the ICU. Patient centeredness was crucial in choosing the outcomes assessed.
Trial registration
ClinicalTrials.gov: . Registered on 25 August 2014. NCT02265458Electronic supplementary material
The online version of this article (doi:10.1186/s13063-016-1574-z) contains supplementary material, which is available to authorized users. 相似文献992.
Objectives
The paper aimed to estimate the incremental cost-effectiveness ratio (ICER) at the public published price for delayed-release dimethyl fumarate versus relevant Multiple Sclerosis disease-modifying therapies available in France in June 2015.Methods
The economic model was adapted to the French setting in accordance with the Haute Autorité de Santé guidelines using a model previously developed for NICE. A cohort of Relapsing Remitting Multiple Sclerosis patients was simulated over a 30-year time horizon. Twenty one health states were taken into account: Kurtzke Expanded Disability Status Scale (EDSS) 0–9 for Relapsing Remitting Multiple Sclerosis patients, EDSS 0–9 for Secondary Progressive Multiple Sclerosis patients, and death. Estimates of relative treatment efficacy were determined using a mixed-treatment comparison. Probabilities of events were derived from the dimethyl fumarate pivotal clinical trials and the London Ontario Dataset. Costs and utilities were extracted from the published literature from both the payer and societal perspectives. Univariate and probabilistic sensitivity analyses were performed to assess the robustness of the model results.Results
From both perspectives, dimethyl fumarate and interferon beta-1a (IFN beta-1a) 44mcg were the two optimal treatments, as the other treatments (IFN beta-1a 30mcg, IFN beta-1b 250mcg, teriflunomide, glatiramer acetate, fingolimod) were dominated on the efficiency frontier. From the societal perspective, dimethyl fumarate versus IFN beta-1a 44mcg incurred an incremental cost of €3,684 and an incremental quality-adjusted life year (QALY) of 0.281, corresponding to an ICER of €13,110/QALY.Conclusions
Despite no reference threshold for France, dimethyl fumarate can be considered as a cost-effective option as it is on the efficiency frontier. 相似文献993.
Sandro?AlvesEmail author Thibaut?Marais Maria-Grazia?Biferi Denis?Furling Martina?Marinello Khalid?El Hachimi Nathalie?Cartier Merle?Ruberg Giovanni?Stevanin Alexis?Brice Martine?Barkats Annie?SittlerEmail author 《Molecular neurodegeneration》2016,11(1):58
Background
We used lentiviral vectors (LVs) to generate a new SCA7 animal model overexpressing a truncated mutant ataxin-7 (MUT ATXN7) fragment in the mouse cerebellum, in order to characterize the specific neuropathological and behavioral consequences of the genetic defect in this brain structure.Results
LV-mediated overexpression of MUT ATXN7 into the cerebellum of C57/BL6 adult mice induced neuropathological features similar to that observed in patients, such as intranuclear aggregates in Purkinje cells (PC), loss of synaptic markers, neuroinflammation, and neuronal death. No neuropathological changes were observed when truncated wild-type ataxin-7 (WT ATXN7) was injected. Interestingly, the local delivery of LV-expressing mutant ataxin-7 (LV-MUT-ATXN7) into the cerebellum of wild-type mice also mediated the development of an ataxic phenotype at 8 to 12 weeks post-injection. Importantly, our data revealed abnormal levels of the FUS/TLS, MBNL1, and TDP-43 RNA-binding proteins in the cerebellum of the LV-MUT-ATXN7 injected mice. MUT ATXN7 overexpression induced an increase in the levels of the pathological phosphorylated TDP-43, and a decrease in the levels of soluble FUS/TLS, with both proteins accumulating within ATXN7-positive intranuclear inclusions. MBNL1 also co-aggregated with MUT ATXN7 in most PC nuclear inclusions. Interestingly, no MBNL2 aggregation was observed in cerebellar MUT ATXN7 aggregates. Immunohistochemical studies in postmortem tissue from SCA7 patients and SCA7 knock-in mice confirmed SCA7-induced nuclear accumulation of FUS/TLS and MBNL1, strongly suggesting that these proteins play a physiopathological role in SCA7.Conclusions
This study validates a novel SCA7 mouse model based on lentiviral vectors, in which strong and sustained expression of MUT ATXN7 in the cerebellum was found sufficient to generate motor defects.994.
Crossing a road safely is a complex task requiring good sensorimotor function and integration of information about traffic speed, distances and one’s own speed. Poor judgement through age-related sensorimotor or cognitive impairment or a predisposition to take risks could lead to errors with serious consequences. On a simulated road, 85 participants (age ≥70 years) were asked to cross in front of an approaching car with a clearance as small as considered safe in two conditions; (1) with nothing else to attend to (free crossing) and (2) with an additional ball-gathering task while waiting to cross (task crossing). Participants were categorised according to their crossing outcome (failed to cross, ‘hit’, exact, safe, cautious). Participants also performed two sub-studies; (1) the perception of the time-to-arrival of moving objects and (2) the perception of own gait speed. Physical and cognitive function and everyday risk-taking behaviour were also assessed. In free crossing, clearances varied but no participants were “hit” by the car. In task crossing, participants allowed smaller clearances and 10% of participants would have been hit while 13% missed the opportunity to cross altogether. Across a wide range of physical and cognitive measures, including perceived and actual gait speed, a consistent pattern was observed in the task crossing condition. The exact group performed best, the ‘hit’, safe and cautious groups performed less well while those who missed the opportunity (fail) performed worst. The exact group reported taking the greatest risks in everyday life whereas the remaining groups reported being cautious. In conclusion, we found older people with poorer perceptual, physical and cognitive function made inappropriate and risky decisions in a divided attention road-crossing task despite self-reports of cautious behaviour in everyday life. 相似文献
995.
Emma Vaughan Annie Le Michaela Casey Kathryn P. Workman Agns Lacreuse 《American journal of primatology》2019,81(9)
Population hand preferences are rare in nonhuman primates, but individual hand preferences are consistent over a lifetime and considered to reflect an individual's preference to use a particular hemisphere when engaged in a specific task. Previous findings in marmosets have indicated that left‐handed individuals tend to be more fearful than their right‐handed counterparts. Based on these findings, we tested the hypotheses that left‐handed marmosets are (a) more reactive to a social stressor and (b) are slower than right‐handed marmosets in acquiring a reversal learning task. We examined the hand preference of 27 male and female marmosets (ages of 4–7 years old) previously tested in a social separation task and a reversal learning task. Hand preference was determined via a simple reaching task. In the social separation task, monkeys were separated from their partner and the colony for a single 7‐hr session. Urinary cortisol levels and behavior were assessed at baseline, during the separation and 24 hr postseparation. Hand preferences were equally distributed between left (n = 10), right‐handed (n = 10), and ambidextrous (n = 7) individuals. The separation phase was associated with an increase in cortisol levels and behavioral changes that were similar across handedness groups. However, cortisol levels at baseline were positively correlated with right‐handedness, and this relationship was stronger in females than in males. In addition, the occurrence of social behaviors (pre‐ and postseparation) was positively correlated with right‐handedness in both sexes. Baseline cortisol levels did not correlate significantly with social behavior. Acquisition of the reversals was poorer in females than males but did not differ as a function of handedness. We conclude that (a) both stress reactivity and cognitive flexibility are similar across handedness groups and (b) left‐handers exhibit less social behavior and have lower basal cortisol levels than ambidextrous and right‐handed subjects. The underlying causes for these differences remain to be established. 相似文献
996.
997.
This study investigated the influence of environmental factors on the foraging cycle, breeding activity, settlement and growth
of the opisthobranch Hydatina
physis using laboratory trials and field observations. Results showed that H. physis follows a nocturnal circadian rhythm mediated by photic intensity and modulated by food availability. The adults foraged
between 1900 and 0530 h, with an activity peak between 2000 and 2200 h, and remained inactive and burrowed in the sand during
the day. This pattern was clearly influenced by cloud cover, rain and laboratory manipulated light:dark cycle. The reproduction
of H. physis was primarily influenced by the lunar cycle. For 4 consecutive months, hermaphroditic reciprocal copulation, preceded by
pre-copulatory courtship behaviour, occurred at night 5–7 d before the full moon. Spawning occurred 3–5 d later for up to
5 consecutive nights, the egg mass gradually decreasing in size with each spawning. An overcast sky or rain prevented or delayed
both copulation and egg release. Settlement of veligers was largely influenced by the nature of the substrate. In multiple-choice
experiments, settlement occurred predominantly on sand containing cirratulid polychaetes. The juveniles reached ca. 3.9 mm
in shell length after 5.5 months growth. 相似文献
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