En collaboration avec mes étudiantes et collègues, je m'intéresse à l'étiologie et au traitement du trouble d'anxiété généralisée (TAG) depuis trois décennies. Lors de mes études doctorales à ...l'Université Laval, notre équipe a élaboré un traitement comportemental et cognitif ayant quatre modules : la réévaluation de l'utilité de s'inquiéter, l'exposition comportementale à l'incertitude, l'entraînement à la résolution de problèmes et l'exposition en imagination. De 1998 à 2013, en tant que professeur à l'Université Concordia et chercheur-clinicien à l'Hôpital du Sacré-Cœur à Montréal, j'ai mené plusieurs essais cliniques montrant que le traitement est efficace pour la majorité des personnes atteintes du TAG et que son mécanisme d'action central est la diminution de l'intolérance à l'incertitude. À l'Université du Québec en Outaouais depuis 2013, je m'intéresse aujourd'hui à la validation d'un nouveau traitement pour le TAG à une seule composante : les expériences comportementales pour l'intolérance à l'incertitude. Les données préliminaires indiquent que le traitement épuré produit des effets similaires à ceux du traitement plus complexe, tout en étant moins coûteux, plus facile à disséminer et plus près des théories d'apprentissage social, des sciences cognitives et de la neuropsychologie. Ainsi, ma démarche scientifique, clinique et universitaire des 30 dernières années m'amène à conclure qu'une intervention psychologique simple et parcimonieuse s'avère préférable lorsque la cible thérapeutique est clairement dégagée. En ce qui concerne le TAG, cette cible est sans contredit la diminution de l'intolérance à l'incertitude.
In collaboration with my students and colleagues of the past three decades, my research and clinical interests have focused on the aetiology and treatment of generalized anxiety disorder (GAD). During my doctoral training at l'Université Laval, our research group developed a cognitive-behavioural treatment that includes four modules: the reevaluation of the usefulness of worry, behavioural exposure to uncertainty, problem-solving training and imaginal exposure. From 1998 to 2013, as professor at Concordia University and scientist-practitioner at l'Hôpital du Sacré-Coeur de Montréal, I conducted a series of clinical trials showing that the treatment is effective for most people with GAD and that the main treatment mechanism is change in intolerance of uncertainty. Given the latter finding, my students and I elaborated a new single-component treatment for GAD: behavioural experiments for intolerance of uncertainty. Since moving to l'Université du Québec en Outaouais in 2013, I have been engaged in testing the new focused treatment. Preliminary data suggest that the single-component treatment produces effects that are similar to those of the earlier multicomponent treatment, while being less costly, easier to disseminate and more closely tied to theories of social learning, cognitive science and neuropsychology. In summary, my work as a scientist, practitioner and teacher over the past 30 years has led me to conclude that simple and parsimonious treatments are preferable in cases where the treatment target is clearly identified. When it comes to clients with GAD, the treatment target seems clear: helping them to increase their tolerance for uncertainty.
There is disagreement about the level of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We conducted a living systematic review and meta-analysis to address ...three questions: (1) Amongst people who become infected with SARS-CoV-2, what proportion does not experience symptoms at all during their infection? (2) Amongst people with SARS-CoV-2 infection who are asymptomatic when diagnosed, what proportion will develop symptoms later? (3) What proportion of SARS-CoV-2 transmission is accounted for by people who are either asymptomatic throughout infection or presymptomatic?
We searched PubMed, Embase, bioRxiv, and medRxiv using a database of SARS-CoV-2 literature that is updated daily, on 25 March 2020, 20 April 2020, and 10 June 2020. Studies of people with SARS-CoV-2 diagnosed by reverse transcriptase PCR (RT-PCR) that documented follow-up and symptom status at the beginning and end of follow-up or modelling studies were included. One reviewer extracted data and a second verified the extraction, with disagreement resolved by discussion or a third reviewer. Risk of bias in empirical studies was assessed with an adapted checklist for case series, and the relevance and credibility of modelling studies were assessed using a published checklist. We included a total of 94 studies. The overall estimate of the proportion of people who become infected with SARS-CoV-2 and remain asymptomatic throughout infection was 20% (95% confidence interval CI 17-25) with a prediction interval of 3%-67% in 79 studies that addressed this review question. There was some evidence that biases in the selection of participants influence the estimate. In seven studies of defined populations screened for SARS-CoV-2 and then followed, 31% (95% CI 26%-37%, prediction interval 24%-38%) remained asymptomatic. The proportion of people that is presymptomatic could not be summarised, owing to heterogeneity. The secondary attack rate was lower in contacts of people with asymptomatic infection than those with symptomatic infection (relative risk 0.35, 95% CI 0.10-1.27). Modelling studies fit to data found a higher proportion of all SARS-CoV-2 infections resulting from transmission from presymptomatic individuals than from asymptomatic individuals. Limitations of the review include that most included studies were not designed to estimate the proportion of asymptomatic SARS-CoV-2 infections and were at risk of selection biases; we did not consider the possible impact of false negative RT-PCR results, which would underestimate the proportion of asymptomatic infections; and the database does not include all sources.
The findings of this living systematic review suggest that most people who become infected with SARS-CoV-2 will not remain asymptomatic throughout the course of the infection. The contribution of presymptomatic and asymptomatic infections to overall SARS-CoV-2 transmission means that combination prevention measures, with enhanced hand hygiene, masks, testing tracing, and isolation strategies and social distancing, will continue to be needed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Le trouble d'anxiété généralisée (TAG) est le seul
trouble anxieux sans critères diagnostiques comportementaux. Dans leur revue des critères
diagnostiques du TAG pour le Diagnostic and Statistical ...Manual of Mental Disorders
(5e éd.; DSM-5; American Psychiatric Association, 2013), Andrews et ses collègues (2010) ont suggéré l'ajout de quatre comportements sécurisants, lesquels n'ont toutefois pas été retenus. À partir de ces recommandations et de notre expérience en pratique clinique, nous avons développé un questionnaire autorapporté de 18 items (le Questionnaire sur les comportements sécurisants du trouble d'anxiété généralisée, QCS-TAG; Hebert & Dugas, 2019) évaluant la présence de comportements sécurisants cliniquement liés au TAG. L'objectif de l'étude est de vérifier la pertinence des 18 items de la version initiale (non validée) et d'examiner les qualités psychométriques du nouvel outil comprenant uniquement les items retenus. Soixante (60) participants ayant un TAG primaire ont été évalués avant et après avoir reçu un traitement cognitivo-comportemental de 12 rencontres, à raison d'une par semaine. La version abrégée de 10 items a montré une bonne cohérence interne (α = 0,78) et une fidélité test-retest acceptable jusqu'à un intervalle de 12 semaines durant une période de liste d'attente, r = 0,64, p < 0,001. Aussi, la validité convergente, divergente et prédictive a été appuyée. Ce questionnaire s'avère donc un outil pertinent pour un contexte clinique et de recherche. Des considérations théoriques pour l'étiologie et la phénoménologie du TAG sont présentées.
Generalised anxiety disorder (GAD) is the only anxiety disorder listed without
behavioural symptoms in the DSM-5. In their review of the GAD diagnostic criteria, Andrews et al. (2010) suggested 4 behavioural symptoms. These symptoms, however, were not retained for the DSM-5. Based on these recommendations and on our clinical experience, we developed an 18-item self-report questionnaire to assess the use of safety behaviours that are associated with GAD (Generalised Anxiety Disorder-Safety Behaviours Questionnaire, GAD-SBQ; Hebert & Dugas, 2019). The aim of this study is to verify the relevance of the 18 items of the initial non validated version and to examine the psychometric properties of the new instrument that includes the selected items only. Sixty (60) participants with primary GAD were evaluated before and after receiving 12 weekly sessions of a cognitive-behavioural treatment. The revised 10-item GAD-SBQ shows good internal consistency (α = .78) and an acceptable 12-week test-retest reliability during a waiting list, r = .64, p < .001. The results also support the convergent, divergent and predictive validity of the questionnaire. Overall, this study supports the relevance of the GAD-SBQ in clinical and research contexts. Implications for the etiology and phenomenology of GAD are also presented.
Intérêt public
Le trouble d'anxiété généralisée (TAG) est caractérisé par la présence d'inquiétudes excessives et incontrôlables. Il s'agit du seul trouble anxieux présenté sans critères diagnostiques comportementaux dans le DSM-5. Afin de mieux comprendre le rôle des comportements dans le TAG, notre équipe a développé un questionnaire évaluant des comportements souvent rapportés par les gens souffrant de ce trouble. Nos résultats suggèrent la pertinence de ce questionnaire pour la pratique clinique, la recherche clinique et, ultimement, pour la santé publique.
L'Échelle de compétence du thérapeute (ÉCT) est un questionnaire évaluant la compétence du thérapeute, telle que perçue par le client lors d'une thérapie comportementale et cognitive. Valider l'ÉCT ...en vérifiant sa structure factorielle, puis en évaluant ses propriétés psychométriques (c.-à-d., sa validité convergente et prédictive), dans un échantillon de 70 participants atteints du trouble d'anxiété généralisée. 1) L'ÉCT et ses deux sous-échelles (Savoir-faire et Savoir-être) présenteront une cohérence interne et une fidélité test-retest satisfaisantes; 2) L'ÉCT sera plus fortement liée à une mesure des caractéristiques du thérapeute qu'à des mesures de l'alliance thérapeutique, de la motivation du client et de la crédibilité du traitement; 3) L'ÉCT fera preuve de validité prédictive. Les participants ont réalisé des mesures de symptômes avant et après 14 séances de traitement, et des mesures de facteurs communs (incluant l'ÉCT) après la 3e et la 11e séance. Douze des 20 items ont été retirés de la version préliminaire de l'ÉCT afin d'obtenir une structure factorielle correspondant à la conceptualisation de l'outil. La version finale à 8 items montre une bonne cohérence interne (α = 0,87) et une stabilité temporelle adéquate (r = 0,51, p < 0,001). Les corrélations significatives observées entre l'ÉCT et d'autres mesures de facteurs communs appuient sa validité convergente. La relation significative et positive entre l'ÉCT et le changement thérapeutique témoigne d'une bonne validité prédictive. L'ÉCT semble donc cliniquement pertinente de par son utilité pour l'évaluation subjective de l'arrimage entre les besoins du client et le service thérapeutique reçu.
The Therapist Competence Scale (TCS) is a questionnaire evaluating the competence of a therapist, as perceived by a client during behavioral and cognitive therapy. The objective of this study is to validate the TCS, in particular by verifying its factorial structure, then evaluating its psychometric properties (its convergent and predictive validity) within a sample of 70 participants with general anxiety disorder. (1) The TCS and its two sub-scales (Technical skills or Savoir-faire, and Interpersonal skills, or Savoir-être) present a good internal coherence and satisfactory test-retest fidelity; (2) the TCS would be more strongly linked to a measure of the characteristics of the therapist than of measurements of therapeutic alliance, client motivation and treatment credibility; and (3) the TCS will prove to have predictive validity. Participants completed assessments of symptoms before and after 14 treatment sessions, and a measurement of common factors (including TCS) following sessions 3 and 11. Twelve of the 20 items were removed from the preliminary version of the TCS to obtain a factorial structure corresponding to the concept of the tool. The final eight-item version shows good internal coherence (a = 0.87) and adequate temporal stability (r = 0.51, p < 0.001). Significant correlation observed between TCS and other measures of common factors support its convergent validity. The significant and positive relationship between TCS and therapeutic change is evidence of good predictive validity. TCS thus seems clinically relevant for its utility in subjective evaluation of the linkage between client needs and therapeutic service received.
Intérêt public
Bien que la compétence du thérapeute joue un rôle dans les progrès thérapeutiques des clients bénéficiant d'une thérapie cognitive-comportementale, peu d'outils se sont avérés efficients pour évaluer cette composante. Dans ce contexte, le développement d'un nouvel outil pratique et valide nous paraît indispensable pour adresser cette lacune.
Humans regulate intergroup conflict through parochial altruism; they self-sacrifice to contribute to in-group welfare and to aggress against competing out-groups. Parochial altruism has distinct ...survival functions, and the brain may have evolved to sustain and promote in-group cohesion and effectiveness and to ward off threatening out-groups. Here, we have linked oxytocin, a neuropeptide produced in the hypothalamus, to the regulation of intergroup conflict. In three experiments using double-blind placebo-controlled designs, male participants self-administered oxytocin or placebo and made decisions with financial consequences to themselves, their in-group, and a competing out-group. Results showed that oxytocin drives a "tend and defend" response in that it promoted in-group trust and cooperation, and defensive, but not offensive, aggression toward competing out-groups.
Over 100 countries have set or are considering net-zero emissions or neutrality targets. However, most of the information on emissions neutrality (such as timing) is provided for the global level. ...Here, we look at national-level neutrality-years based on globally cost-effective 1.5 °C and 2 °C scenarios from integrated assessment models. These results indicate that domestic net zero greenhouse gas and CO
emissions in Brazil and the USA are reached a decade earlier than the global average, and in India and Indonesia later than global average. These results depend on choices like the accounting of land-use emissions. The results also show that carbon storage and afforestation capacity, income, share of non-CO
emissions, and transport sector emissions affect the variance in projected phase-out years across countries. We further compare these results to an alternative approach, using equity-based rules to establish target years. These results can inform policymakers on net-zero targets.
As of 16 May 2020, more than 4.5 million cases and more than 300,000 deaths from disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported. Reliable estimates ...of mortality from SARS-CoV-2 infection are essential for understanding clinical prognosis, planning healthcare capacity, and epidemic forecasting. The case-fatality ratio (CFR), calculated from total numbers of reported cases and reported deaths, is the most commonly reported metric, but it can be a misleading measure of overall mortality. The objectives of this study were to (1) simulate the transmission dynamics of SARS-CoV-2 using publicly available surveillance data and (2) infer estimates of SARS-CoV-2 mortality adjusted for biases and examine the CFR, the symptomatic case-fatality ratio (sCFR), and the infection-fatality ratio (IFR) in different geographic locations.
We developed an age-stratified susceptible-exposed-infected-removed (SEIR) compartmental model describing the dynamics of transmission and mortality during the SARS-CoV-2 epidemic. Our model accounts for two biases: preferential ascertainment of severe cases and right-censoring of mortality. We fitted the transmission model to surveillance data from Hubei Province, China, and applied the same model to six regions in Europe: Austria, Bavaria (Germany), Baden-Württemberg (Germany), Lombardy (Italy), Spain, and Switzerland. In Hubei, the baseline estimates were as follows: CFR 2.4% (95% credible interval CrI 2.1%-2.8%), sCFR 3.7% (3.2%-4.2%), and IFR 2.9% (2.4%-3.5%). Estimated measures of mortality changed over time. Across the six locations in Europe, estimates of CFR varied widely. Estimates of sCFR and IFR, adjusted for bias, were more similar to each other but still showed some degree of heterogeneity. Estimates of IFR ranged from 0.5% (95% CrI 0.4%-0.6%) in Switzerland to 1.4% (1.1%-1.6%) in Lombardy, Italy. In all locations, mortality increased with age. Among individuals 80 years or older, estimates of the IFR suggest that the proportion of all those infected with SARS-CoV-2 who will die ranges from 20% (95% CrI 16%-26%) in Switzerland to 34% (95% CrI 28%-40%) in Spain. A limitation of the model is that count data by date of onset are required, and these are not available in all countries.
We propose a comprehensive solution to the estimation of SARS-Cov-2 mortality from surveillance data during outbreaks. The CFR is not a good predictor of overall mortality from SARS-CoV-2 and should not be used for evaluation of policy or comparison across settings. Geographic differences in IFR suggest that a single IFR should not be applied to all settings to estimate the total size of the SARS-CoV-2 epidemic in different countries. The sCFR and IFR, adjusted for right-censoring and preferential ascertainment of severe cases, are measures that can be used to improve and monitor clinical and public health strategies to reduce the deaths from SARS-CoV-2 infection.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Exosomes are nano-sized vesicles secreted by most cells that contain a variety of biological molecules, such as lipids, proteins and nucleic acids. They have been recognized as important mediators ...for long-distance cell-to-cell communication and are involved in a variety of biological processes. Exosomes have unique advantages, positioning them as highly effective drug delivery tools and providing a distinct means of delivering various therapeutic agents to target cells. In addition, as a new clinical diagnostic biomarker, exosomes play an important role in many aspects of human health and disease, including endocrinology, inflammation, cancer, and cardiovascular disease. In this review, we summarize the development of exosome-based drug delivery tools and the validation of novel biomarkers, and illustrate the role of exosomes as therapeutic targets in the prevention and treatment of various diseases.
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