Effect of Bright Light Therapy on Perinatal Depression: A Systematic Review and Meta-Analysis: Effet de la luminothérapie sur la dépression périnatale: une revue systématique et une méta-analyse.

OBJECTIVE: This study represents the inaugural attempt to systematically review and analyse the efficacy of bright light therapy on depression among women experiencing major depressive disorder or depressive symptoms during the perinatal period, encompassing its efficacy on depression scores, remission rates, and response rates. METHODS: We searched 10 databases for randomized controlled trials examining bright light therapy's efficacy on perinatal depression up to January 2024. Data extraction was performed independently by 2 investigators. The Cochrane Handbook guidelines appraised the study quality, and the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach assessed evidence certainty. RESULTS: We incorporated 6 studies, encompassing 151 participants. When contrasted with dim light therapy, bright light therapy did not significantly alter depression scores (standard mean difference = -0.29, 95% confidence interval [CI], -0.62 to 0.04, P = 0.08, I² = 34%) or response rates (risk ratio [RR] = 1.56, 95% CI, 0.98 to 2.49, P = 0.06, I² = 0%) in women experiencing perinatal depression. Conversely, bright light therapy was associated with a substantial increase in remission rates (RR = 2.63, 95% CI, 1.29 to 5.38, P = 0.008, I² = 2%). CONCLUSION: Bright light therapy did not show efficacy in treating perinatal depression in terms of depression scores and response rates. However, regarding the remission rate, bright light did show efficacy compared to control conditions. Due to the limited sample size in the included studies, type II err or may occur. To obtain more conclusive evidence, future studies must employ larger sample sizes.

[Effectiveness of psychotherapy on dissociative symptoms in adult populations: A PRISMA systematic review]. / Efficacité des psychothérapies sur les symptômes dissociatifs en population adulte : une revue de la littérature PRISMA.

INTRODUCTION: Dissociation is a psychological process in reaction to threat which can be found in many psychiatric conditions. Dissociative symptoms can become very disabling, whether in daily life or in care. Nevertheless, few studies seem to have examined the efficacy of psychotherapy on the latter and its relevance as a therapeutic target. METHOD: A systematic review of the literature (PRISMA) on the efficacy of psychotherapy on dissociative symptoms in adults with mental disorders was conducted. Effectiveness was considered in terms of reduction in dissociative symptomatology. The search was conducted on Scopus, PubMed and PsycInfo. Overall, 50 full-text articles were evaluated. RESULTS: Fourteen studies were included in the review. In all, 711 adult subjects with post-traumatic stress disorder, borderline personality disorder or dissociative disorder were included. Overall, this systematic review reports a reduction in dissociative symptoms associated with a variety of psychotherapeutic interventions, without allowing any conclusions to be drawn on the superiority of one psychotherapy over another. DISCUSSION: The conclusions of this work highlight three possible therapeutic orientations for reducing dissociative symptoms: (i) by reintegrating the dynamic subsystems, (ii) by treating the cognitive processes underlying dissociation, and (iii) by acting on the processes identified as common to the effectiveness of psychotherapy.

Prevalence of prolonged grief disorder in bereaved children and adolescents: A systematic review.

PURPOSE: Prolonged Grief Disorder (PGD) is a condition recently introduced in international classifications of mental disorders. Although PGD is associated with significant distress and impairment that may have developmental consequences, to date, little is known about its prevalence and associated factors in children and adolescents. The present systematic review registered in PROSPERO (CRD42021236026) aimed to: (i) review existing data on the prevalence of PGD in bereaved children and adolescents; and (ii) identify factors associated with PGD in this population. METHODS: Six electronic databases, grey literature and a manually searched journal identified 1,716 articles with no backward limit to September 2021. Epidemiological studies were included if they reported the prevalence of PGD in bereaved children and adolescents. Study characteristics, diagnostic and assessment tools, population, loss-related characteristics and prevalence of PGD were reviewed. RESULTS: Five studies met our inclusion criteria. The reported prevalences of PGD ranged from 10.4% to 32%. Female gender, cognitive avoidance, chronic stressors such as economic hardship, exposure to trauma or other losses appear to be associated with more severe symptoms or even a higher risk of PGD. Conversely, data suggest social support may be protective. CONCLUSION: This first systematic review found a relatively high prevalence of PGD in bereaved children and adolescents. While further large epidemiological studies are needed, this review highlights the importance of evaluating PGD in current clinical practice and suggests that further research into diagnostic and therapeutic approaches targeting this disorder is warranted.

[Prevalence of mental disorders in French prisons: A systematic review]. / Prévalence des troubles psychiatriques en population carcérale française : une revue systématique de la littérature.

INTRODUCTION: The prevalence of psychiatric disorders among prisoners remains a major public health issue worldwide. In France, despite the increasing number of persons who are incarcerated (+30% between 1992 and 2002 with a 120% prison overcrowding), and a historical concern about the mental health of persons in detention and its management, no systematic review has been published on this subject. The aim of this article is to present the results of a systematic review of the literature on the prevalence of psychiatric disorders in French prisons. METHOD: The reporting of this systematic review conforms to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) checklist. We searched the PubMed and Web of Science databases. We used combinations of keywords relating to prison (prison*, jail*, inmate*), to psychiatry ("mental health", psychiatr*), and to France (France, French). This work was completed with a search through the digital libraries of the École des Hautes Études en Santé Publique (EHESP) and of the Système Universitaire de Documentation (Sudoc) to obtain data from academic works and the gray literature. References cited in studies included in this review were also examined. All references published up to September 2022, written in English or French, presenting the results of original quantitative studies on the prevalence of psychiatric disorders in correctional settings were included. Two researchers independently extracted data from included references according to a pre-established protocol. RESULTS: Among 501 records identified, a total of 35 papers based on 24 epidemiological studies met the eligibility criteria for inclusion in this review: 16 were cross-sectional, 7 retrospective and 1 both cross-sectional and retrospective. All papers were published between 1999 and 2022. We found one European study, 5 international studies, 18 regional or local studies. Of these, 21 studies had all-male or mixed gender samples (but when the sample was mixed gender, it was always at least 92% male). Almost half of the studies (n=11) involved a small sample of fewer than 500 persons. Half of the studies involved a sample of recently incarcerated persons: 6 involved a random sample of persons in detention, and 1 involved a sample of people incarcerated for more than 5 years. The last 5 studies focused on persons aged over 50 years and incarcerated for more than one year (n=1), incarcerated for sexual offences (n=2), placed in disciplinary cells (n=1) or in a special wing for radicalized or suspected radicalized individuals (n=1). Nine studies used standardized and validated diagnostic tools. According to the 4 studies involving representative samples and using standardized and validated diagnostic tools, the prevalence of the following psychiatric disorders was: 29.4-44.4% for anxiety disorders, 5-14.2% for PTSD, 28-31.2% for mood disorders, 6.9-17% for psychotic disorders, 32% for personality disorders and 11% for ADHD. CONCLUSION: This systematic review of the literature highlights the high prevalence of psychiatric disorders in French prisons. The data collected are in line with international studies. The great methodological heterogeneity of the papers included in this review calls for further rigorous research to better understand the rates of mental disorders in French prisons and to explore their determinants.

Updating the evidence: A systematic review of a decade of Infant and Early Childhood Mental Health Consultation (IECMHC) research.

Infant and Early Childhood Mental Health Consultation (IECMHC) is a preventative, capacity-building intervention in which mental health professionals partner with early childhood professionals to indirectly improve the environments and relationships that young children experience. Prior research has demonstrated that IECMHC is associated with positive outcomes for children, teachers, and classrooms. Over the past decade, IECMHC implementation and research have expanded, warranting an updated review. The current paper provides an update of the IECMHC evidence base. Included studies (n = 16) were systematically gathered, screened, and coded for context, intervention characteristics, methods and measures, outcomes across ecological levels, and alignment with the IDEAS Impact Framework's guiding questions. Our analysis replicates prior reviews, describing the positive impact of IECMHC on outcomes such as child externalizing behavior, teacher self-efficacy, and teacher-child interactions. Beyond updating prior reviews, this analysis describes emerging, nuanced findings regarding the mechanisms of change and the differential impact of IECMHC. We augment our review with descriptions of evaluations that did not meet our inclusion criteria (e.g., IECMHC in the home visiting context, unpublished evaluation reports) to provide context for our findings. Finally, we provide policy and practice implications and articulate an agenda for future research.

Cervical cancer in Morocco: A systematic review.

BACKGROUND: This systematic review aims to determine the epidemiological profile, etiology and risk factors, prevention, diagnosis, treatment, cost-effectiveness, survival, and quality of life related to cervical cancer in Morocco. METHODS: This study was conducted according to the recommendations of the "preferred reporting items for systematic reviews and meta-analysis." The PubMed, ScienceDirect, Springer, Web of Science data bases were used, as was Google Scholar for the grey literature. The review protocol was registered in the PROSPERO register (CRD42021235241). RESULTS: Fifty studies were selected. The mean age was 49.31 ±6.3 years. HPV infection prevalence ranged from 13.30% to 76%, with a peak in HIV-positive women. Acceptability of the HPV vaccine was higher among parents (35% and 82%) than among adolescents (16.9% to 46.6%). Knowledge of the vaccine and its price are two key factors related to vaccine acceptability among parents. This systematic review highlights that the fact that few eligible women (not more than 11%) were participating in the cervical cancer screening program. Moroccan women's level of knowledge and awareness regarding cervical cancer screening was low, negatively impacting their use of such screening tools, as illustrated by the high percentage (mean 76.32% ± 17.21) of women who had never been screened for cervical cancer. Treatment was the most significant component of the global care budget (95.87%), with an annual cost of $13,027,609. Five-year overall survival ranged from 41.3% to 73.6%, with higher survival rates for patients diagnosed at an earlier stage (77.3-85% for stage I). Lastly, low quality of life was observed in women with tumors at an advanced stage who had received brachytherapy and lacked social support. CONCLUSIONS: Subjects that require further investigation include Moroccan women's knowledge, attitudes, and awareness, especially among those at high risk of developing cervical cancer, and its impact on their quality of life and survival.

Patient-Reported Outcome and Experience Measures Administered by Dietitians in the Outpatient Setting: Systematic Review.

Understanding how patients perceive their health and the experience with the dietitian is fundamental to providing patient-centred care. The types of patient reported measures (PRMs) used by outpatient dietitians is unclear. Guidance about use of PRMs for dietitians is also lacking. The aim of this systematic review was to synthesise evidence regarding the use of PRMs by dietitians in the outpatient setting and evaluate the methodological quality of studies evaluating the psychometric properties of PRMs. Eight databases were searched systematically for studies of dietitians working in the outpatient setting and administering a PRM. Forty-four studies were evaluated and described 58 different PRMs. These included direct nutrition related (n = 12 studies), clinical (n = 21 studies), and health-related quality of life PRMs (n = 24 studies); 1 study documented use of a patient-reported experience measure. A large range of PRMs are used by outpatient dietitians. Of the most common PRMs, the majority are administered in similar populations to the original validation study. Dietitians should use a combination of 3 PRMs: a generic health-related quality of life tool, an experience measure, and at least 1 clinical or direct nutrition-related measure. This will enable dietitians to fully capture the impact of their care on patients.

[Measuring adolescents' use of social media: A systematic review]. / La mesure de l'usage des réseaux sociaux chez les adolescents: une revue systématique de la littérature.

OBJECTIVE: The purpose of this review was to provide an overview of the methods used to measure social network site use among adolescents. Such a review is important given the number and diversity of sites and the prevalence of their use among adolescents. METHODS: A systematic review of the literature was conducted in line with PRISMA guidelines to arrive at an analysis of 58 peer-reviewed studies indexed in PubMed, PsychInfo, or Scopus. To be included in the review, articles had to be peer-reviewed, available in full text, and published in French or English. For inclusion, studies were required to pertain to adolescents aged between 11 and 18 years; to focus on social network site use and indicate how their use was estimated. Studies that simultaneously examined social network sites and general internet use or video games and only provided a combined analysis were excluded. The keywords for the search were: social media use, social media usage, social media misuse, measure, teen, and adolescents. RESULTS: In the literature, different methods were used to operationalize the use of social network sites: quantitative methods with the measurement of frequency and duration of use of social network sites, and qualitative methods to measure the different activities adolescents engage in on such sites. In this review, 28 articles investigated the use of social media through a measurement of frequency and 22 articles through a measurement of the duration of use. Most of the studies focused on social network sites in general, without specifying which sites in particular were considered by the respondents when answering the question. However, some articles provided cross measures of quantitative and qualitative measurements resulting in the examination of both the frequency of use and the time spent on specific activities on social network sites. CONCLUSIONS: The present review highlights the great diversity in the methods used to measure the use of social network sites among adolescents. The reliance on frequency-based measurements without taking into account the specificities of the activities or sites involved limits the investigation of their impact on adolescent functioning and behaviors. Given the observed discrepancies in the literature concerning the measurement of social network site use among adolescents and their associated biases, the development of specific instruments is needed to advance in this important field of research.

[The efficacy of esketamine in resistant major depressive disorder: A systematic review of the literature]. / L'efficacité de l'eskétamine dans le trouble dépressif majeur résistant : une revue systématique de la littérature.

OBJECTIVE: Major depression is a significant public health problem since its lifetime prevalence is estimated at 15-18 %. Its standard treatment is based on the use of antidepressant medications but their effectiveness is limited. Indeed, only two thirds of patients with a major depressive episode will reach remission after two lines of conventional treatment. In major depression, there are arguments in favour of disturbances in neuronal glutamatergic transmission. Esketamine appears to have an antidepressant action through modulation of the NMDA receptors involved in this glutamatergic neurotransmission. The aim of this review to systematically investigate the efficacy of esketamine combined with an SSRI or SNRI for major depressive disorder resistant to treatment. METHOD: A systematic review on the efficacy of esketamine in combination with an SSRI or SNRI for resistant major depressive disorder was performed in July 2021 in the PUBMED database according to the PRISMA criteria. The key words used are: "depressed" [All Fields] OR "depression" [MeSH Terms] OR "depression" [All Fields] OR "depressions" [All Fields] OR "depression s" [All Fields] OR "depressive disorder"[MeSH Terms] OR ("depressive"[All Fields] AND"disorder"[All Fields]) OR"depressive disorder"[All Fields] OR"depressivity"[All Fields] OR"depressive"[All Fields] OR "depressively" [All Fields] OR "depressiveness" [All Fields] OR "depressives" [All Fields]) AND ("esketamine" [Supplementary Concept] OR "esketamine" [All Fields] OR "esketamine" [All Fields]. The inclusion criteria were: efficacy on depressive symptoms of intranasal esketamine combined with an SSRI or an SNRI for major depressive disorder resistant to at least two lines of treatment, RCT and meta-analysis, individual≥18 years, articles in English and French. RESULTS: Four randomized double-blind studies were selected on the basis of these criteria. The included studies are of grade A and B which leads to a high level of scientific evidence. CONCLUSIONS: Intranasal esketamine in combination with sertraline, escitalopram, duloxetine or venlafaxine prolonged release is more effective than the monotherapy use of these four molecules for the treatment of resistant depression. It has been shown to be effective for a population aged between 18 and 74 years at doses between 28mg and 84mg. Currently, based on these results, intranasal esketamine should be proposed as a second level of treatment after an unsuccessful trial of two antidepressants. It is nevertheless advisable to be careful in its use in a clinical psychiatric population: exclusion of suicidal ideation or antecedent of suicidal acting, absence of psychotic depression, use exclusively for unipolar major depressive disorder. The different conditions of use are also notified in the product characteristics of the European Medicines Agency. Finally, further comparative studies are needed in the future, in the absence of funding from the pharmaceutical company producing esketamine.

[Investigating the relationship between social media use and body image among adolescents: A systematic review]. / Lien entre usage des réseaux sociaux et image corporelle chez les adolescents : une revue systématique de la littérature.

OBJECTIVES: This study aimed to update the scientific knowledge concerning the relationship between the use of social networking sites and body image among adolescents. METHODS: A preregistered systematic review was conducted following PRISMA guidelines and allowed to include 30 peer-reviewed articles for qualitative analysis, consisting of 26 unique samples (n=31,331; Mage=14.89; SDage=1.07). The search was conducted on Pubmed, PsychInfo and Scopus focusing on studies that included any social network site use and body image measures while being based on general population adolescent samples. Social networking site use referred: 1) to any online activities such as browsing, posting, editing selfies, liking, commenting; 2) to any exposure to appearance-related content; or 3) to a measure of frequency use. The scope of social networking sites considered in the present review was extended to online video-sharing platforms and online dating applications due to their relationship with appearance. Body image as considered through MeSH terms referred to a wide range of possible outcomes including body and facial dissatisfaction, dysmorphophobia, body surveillance, self-objectification, body shame, weight concerns, self-monitoring. Any mental health outcome was extracted when available although its absence was not an exclusion criterion.. RESULTS: Among the 30 studies included in the review, 22 were cross-sectional, seven were longitudinal and one had an experimental design. Overall, among studies based on unique samples, 18 studies included both males and females (n=28,081; Mage 14.84; SDage=1.06), seven were based exclusively on female samples (n=2,507; Mage 14.87; SDage=1.19), while one study recruited only male adolescents (n=743; Mage 15.90; SDage=0.54). Only six studies were based on representative samples. These studies reported a robust association between frequency of social networking site use and negative body image among both females and males. In addition, exposure to appearance-related content was also deleterious to body image. The association between the use of social media and negative body image may involve negative mental health outcomes, such as depressive symptoms, low body esteem and problematic use of social media. Measuring specific activities on social network sites or exposure to appearance-related content (e.g. selfies editing; selfies posting) may be more accurate than using a frequency of overall use (e.g. during the past month) when predicting body image. Studies addressing underlying processes supported that the relationship between use of social media and body image may not be direct but rather involve intermediary steps on both cognitive and social levels, namely internalization of the thin ideal, self-objectification, peer appearance-related feedback, ascendant social comparison with peers and celebrities. Also, it remains unclear whether mental health mediates this relationship. CONCLUSIONS: The association between the use of social networking sites and negative body image is robustly supported in the literature. However, studies measuring frequency of overall use may instead be predicting negative body image with a nested measure of the use of social network sites, namely specific activities involving appearance-related content. Due to the observed discrepancies between self-reported frequency of social networking site use and actual use in methodological literature, future research may rather measure behaviors commonly encountered on a given platform. Furthermore, there is a need to distinguish specific site categories such as highly visual social media when focusing on body image outcomes. . Focusing on specific social media platforms may in turn lead to more targeted prevention regarding a safe utilization of social networking sites among adolescents. Despite the growing body of research concerning the association between social media and body image, the current review underlines that additional longitudinal and experimental studies are needed to investigate potential bidirectional effects, as well as studies based on representative samples to improve generalization to adolescent populations.

Evidence from systematic reviews of randomized trials on enteral lactoferrin supplementation in preterm neonates.

In this commentary, we summarize the current evidence from randomized controlled trials on enteral lactoferrin supplementation in preterm neonates. Our recently completed systematic review includes 12 randomized controlled trials performed all over the world. Our meta-analysis suggests clinical benefit in decreasing late-onset sepsis, late-onset fungal sepsis, length of stay in the hospital and urinary tract infections. There were no adverse effects. There was no statistically significant decrease in necrotizing enterocolitis, mortality or neurodevelopmental impairment in lactoferrin supplemented preterm infants. There was significant statistical heterogeneity in the effects of lactoferrin on late-onset sepsis between larger and smaller studies, which may reflect either small study biases, differences in the effectiveness, dose or duration of supplemental lactoferrin products, or differences in underlying population risk, or any or all of these.

Enhancing parental reflective functioning through early dyadic interventions: A systematic review and meta-analysis.

Parental reflective functioning (PRF) is an important predictor of infant attachment, and interventions that target parent-infant/toddler dyads who are experiencing significant problems have the potential to improve PRF. A range of dyadic interventions have been developed over the past two decades, some of which explicitly target PRF as part of their theory of change, and some that do not explicitly target PRF, but that have measured it as an outcome. However, no meta-analytic review of the impact of these interventions has been carried out to date. The aim of this review was to evaluate the effectiveness of dyadic interventions targeting parents of infant and toddlers, in improving PRF and a number of secondary outcomes. A systematic review and meta-analysis was conducted in which key electronic databases were searched up to October 2018. Eligible studies were identified and data extracted. Data were synthesised using meta-analysis and expressed as both effect sizes and risk ratios. Six studies were identified providing a total of 521 participants. The results of six meta-analyses showed a nonsignificant moderate improvement in PRF in the intervention group (standardised mean difference [SMD]: -0.46; 95% confidence interval [CI] [-0.97, 0.04]) and a significant reduction in disorganised attachment (risk ratio: 0.50; 95% CI [0.27, 0.90]). There was no evidence for intervention effects on attachment security (odds ratio: 0.71; 95% CI [0.19, 2.64]), parent-infant interaction (SMD: -0.10; 95% CI [-0.46, 0.26]), parental depression (SMD: -1.55; 95% CI [-3.74, 0.64]) or parental global distress (SMD: -0.19, 95% CI [-3.04, 22.65]). There were insufficient data to conduct subgroup analysis (i.e. to compare the effectiveness of mentalisation-based treatment with non-mentalization-based treatment interventions). Relational early interventions may have important benefits in improving PRF and reducing the prevalence of attachment disorganisation. The implications for future research are discussed.

El funcionamiento de reflexión del progenitor (PRF) es un factor importante de predicción de la afectividad del infante, y las intervenciones que se enfocan en díadas progenitor/infante/niño pequeñito que experimentan problemas significativos tienen la posibilidad de mejorar el PRF. La meta de esta revisión fue evaluar la eficacia de las intervenciones diádicas que se enfocan en los progenitores de infantes y niños pequeñitos, para mejorar el PRF y un número de resultados secundarios. Se llevó a cabo una revisión sistemática y un meta-análisis en los que se investigaron bancos de información electrónica claves hasta octubre de 2018. Se identificaron estudios elegibles y se sacó de ellos la información. Se sintetizó esa información usando meta-análisis y la misma fue presentada tanto en términos de dimensión de efectos como la proporción de riesgo. Se identificaron seis estudios que aportaron un total de 521 participantes. Los resultados de seis meta-análisis mostraron un moderado, poco significativo y limítrofe mejoramiento en cuanto al PRF en el grupo de intervención (SMD: -0.46; 95% CI -0.97, 0.04), una reducción significativa en la afectividad desorganizada (RR: 0.50; 95% CI: 0.27, 0.90), pero no así en la afectividad segura (OR: 0.71; 95% CI: 0.19, 2.64), y ninguna evidencia de beneficio para la interacción progenitor-infante (SMD: -0.09; 95% CI: -0.51, 0.32). Se dio un mejoramiento grande no significativo en la depresión del progenitor (SMD: -1.55; 95% CI -3.74, 0.64), pero no hubo evidencia de beneficio en cuanto a la angustia total (SMD: -0.19; 95% CI: -3.04, 22.65). Se discuten las implicaciones para la futura investigación.

Le fonctionnement parental réfléchi (en anglais Parental Reflective Functioning, soit PRF) est un facteur de prédiction important de l'attachement du bébé, et les interventions qui ciblent les dyades parent-bébé/petit enfant qui font l'expérience de problèmes importants ont le potentiel d'améliorer le fonctionnement PRF. Le but de cette article était d'évaluer l'efficacité d'interventions dyadiques ciblant les parents de bébés et de petits enfants, en améliorant le fonctionnement PRF et un bon nombre de résultats secondaires. Une revue et une méta-analyse ont été faites, les bases de données électroniques clés ayant été passées au crible en octobre 2018. Les études pouvant être utilisées ont été identifiées et les données ont été extraites. Les données ont été synthétisées en utilisant une méta-analyse et exprimées sous forme d'ampleur de l'effet et de risque relatif. Six études ont été identifiées, pour un total de 521 participants. Les résultats de six méta-analyses ont montré une amélioration limite non importante modérée dans le PRF dans le groupe d'intervention (SMD: -0,46; 95% CI -0,97, 0,04), une réduction importante dans l'attachement désorganisé de l'enfant (RR: 0,50; 95% CI: 0,27, 0,90) mais non dans l'attachement sécure (OR: 0,71; 95% CI: 0,19, 2,64), ainsi qu'aucune preuve de bénéfice pour l'interaction parent-bébé (SMD: -0,09; 95% CI -0,51, 0,32). Il y avait une grande amélioration non-importante dans la dépression parentale (SMD: -1,55; 95% CI -3,74, 0,64) mais aucune preuve de bénéfice dans la détresse globale (SMD: -0,19; 95% CI: -3,04, 22,65. Les implications pour les recherches futures sont discutées.

[Efficacy of psychedelics in psychiatry, a systematic review of the literature]. / Efficacité des psychédéliques en psychiatrie, une revue systématique.

OBJECTIVES: Psychedelics are powerful psychoactive substances. Natural psychedelics have been used for millennia by human civilizations, in particular in Latin America, while synthetic psychedelics were discovered in the 50s, giving rise to a lot of research before they were prohibited. More recently, their therapeutic properties have been studied especially to help patients with psychiatric conditions, psychological distress or substance use disorders. This article is a systematic review of the literature which aims to provide an overview of all studies that assessed the efficacy of psychedelics, i.e. psilocybin, ayahuasca and lysergic acid diethylamide (LSD), on psychiatric diseases and addictions. METHODS: We conducted this literature review following the PRISMA recommendations. MEDLINE, PsycInfo, Web of Science and Scopus were searched from January 1990 to May 2020 with the following keywords "(ayahuasca OR psilocybin OR lysergic acid diethylamide) AND (depression OR anxiety OR major depressive disorder OR bipolar disorder OR anxiety disorder OR substance use disorder OR dependence)". RESULTS: Twenty-five articles met the inclusion criteria. Five articles studied psychedelic efficacy in the treatment of life-threatening diseases related to anxiety and depression: four were randomized controlled crossover trials (three with psilocybin for a total of 92 patients, and one with LSD, n=12), and one was a long-term follow-up study. Eleven articles explored the efficacy of psychedelics in the treatment of major depressive episodes: two were open-labeled trials (one with ayahuasca, n=17, one with psilocybin, n=20), one was a randomized controlled trial using ayahuasca against placebo (n=29), and the others were long-term follow-up studies or assessed more precise dimensions of the depressive disorder, such as suicidality, emotion processing or personality traits. Eight articles studied the efficacy of psychedelics in the treatment of addictions: two were open-labeled studies using psilocybin (one in alcohol use disorder, n=10, and one in tobacco use disorder, n=15), and the others were long-term follow-up studies or retrospective observational descriptive studies on alcohol, tobacco, opioids, cannabis, and psychostimulants. One study explored the efficacy of psilocybin in obsessional-compulsive disorder (n=9). Overall, these studies found a quick and important response after psychedelic administration that lasted for several months, even after a single dose. However most of these studies were descriptive or open-label studies conducted on small size samples. No severe adverse events occurred. CONCLUSIONS: Psychedelics are promising treatments for anxiety, depression and addiction, their efficacy is quick and sustainable, and they are well tolerated. These effects need to be confirmed in larger studies and compared to standard care.

[Efficacy of psychodynamic therapies: A systematic review of the recent literature]. / L'efficacité des psychothérapies inspirées par la psychanalyse : une revue systématique de la littérature scientifique récente.

AIM: A French governmental institute published, in February 2004, a report assessing the efficacy of psychotherapies in the light of the biomedical literature. It concluded that cognitive psychotherapies effectively cure common mental disorders, while the efficacy of psychodynamic therapies is not proven by scientific studies. Because many French mental health professionals are practicing with reference to psychoanalysis, this conclusion stirred up heated controversy. Since February 2004, numerous studies assessing psychodynamic therapies have been published in peer-reviewed biomedical journals. Moreover, these primary studies have been meta-analyzed in dozens of review articles. Here, we systematically review these meta-analysis articles. METHODS: A systematic search for meta-analyses assessing psychodynamic therapies was performed using PubMed and identified 71 articles published from January 2004 to December 2019. Among them, 25 articles were judged to be relevant because they reported meta-analyses assessing the symptoms of common mental disorders in at least three distinct cohorts of adult patients. Although the primary studies included in these 25 meta-analysis articles often overlap, the selection criteria, calculation methods and results always differ between them. Therefore, we reviewed all of them without further selection. From all the meta-analyses reported in these 25 articles, we systematically present here the most compelling ones, i.e. those calculated from the largest number of primary studies. Results were quantified in terms of effect size (i.e. standardized mean difference). Effect sizes below 0.25 were considered as without clinical significance, whereas those superior to 0.8 were regarded as robust. Because short-term psychodynamic therapies had been assessed in 20 meta-analysis articles published until 2017, we did not search for more recent primary studies. However, because the most recent meta-analysis article about long-term psychodynamic therapies was published in 2013, we also searched, using PubMed, for primary studies assessing psychodynamic therapies lasting for at least one year and published from January 2013 to December 2019. Among the 57 publications retrieved by PubMed, three were identified as randomized controlled trials not included in meta-analyses and were extensively described here. RESULTS: Eight meta-analysis articles have assessed symptom improvement at treatment termination by comparing with baseline symptoms. According to all of them, psychodynamic therapies alleviate symptoms and their effect sizes are always robust. Three meta-analysis articles compared psychodynamic therapies with inactive treatments (e.g. placebo medication, waiting list) and reported clinically significant differences in favor of psychodynamic therapies. Ten meta-analysis articles compared, at treatment termination, psychodynamic therapies to active treatments, including medication and cognitive psychotherapies. Nine of them reported no difference. Only one article concluded that psychodynamic therapies are clinically inferior to cognitive psychotherapies (d=-0.28). Seven meta-analysis articles compared psychodynamic therapies to active treatment at follow-up (i.e. months or years after treatment termination). Five of them reported no significant difference, one reported a medium effect size in favor of psychodynamic therapies over various active treatments (d=0.38), while the other reported a clinically significant difference in favor of cognitive psychotherapies (d=-0.55). Because short-term treatments are often insufficient to prevent relapse, investigations about long-term treatments (i.e. more than one year) are needed, but such published studies are still scarce. Five meta-analysis articles and three primary studies published since 2013 compared long-term psychodynamic therapies to various active treatments of similar duration. According to them, psychodynamic therapies were at least as effective as other active treatments. CONCLUSION: A systematic review about psychodynamic therapies, published in 2015 in Lancet Psychiatry, included 64 randomized controlled trials of which 37 were published after 2003. Therefore, most quality studies assessing psychodynamic therapies have been published since 2003 and have been reviewed in recent meta-analysis articles. All together, this recent literature leads to the conclusion that psychodynamic therapies are as effective as active treatments, including cognitive psychotherapies, to help patients suffering from common mental disorders (unipolar depression, anxiety disorders, eating disorders and personality disorders). Beside this overall conclusion, it appears that randomized controlled trials are not well suited for answering why psychotherapies work in some patients but not in others, and how they work in general. Other approaches are needed, including case studies.

The process of implementing child mortality reviews in low- and middle-income countries: a narrative systematic review.

OBJECTIVES: This review aims to describe the processes that have been used to implement child mortality reviews in LMICs and to identify the facilitators and barriers to their implementation and impact. This will help to inform healthcare professionals and managers planning to implement a child mortality review in their setting. METHODS: MEDLINE and Embase databases were searched for papers published between January 1996 and April 2019. Studies reporting the implementation of a child mortality review process in LMICs were considered eligible. A narrative approach was used to describe the stages in the audit process outlined in the WHO 'Operational guide for facility-based audit and review of paediatric mortality' which were completed, and to synthesise the barriers and facilitators to implementation and impact of the child mortality review process. RESULTS: From 776 potentially relevant articles, seven studies were included. In six studies, problems contributing to child deaths and possible solutions were identified, in four, these solutions were implemented, and in one, this implementation was monitored. Key factors influencing implementation and impact were attendance at meetings, use of a blame-free approach, allocating adequate human and financial resources to make changes, and level of engagement from leadership. CONCLUSIONS: Despite the common use of mortality reviews in paediatric departments, there are few studies published on this topic. The transition from identifying problems and solutions to implementing and monitoring action plans appears to be the most difficult aspect of the process, which requires commitment of adequate resources and strong leadership.

OBJECTIFS: Cette analyse vise à décrire les processus qui ont été utilisés pour mettre en œuvre des analyses de la mortalité infantile dans les PRFI et pour identifier les facilitateurs et les obstacles à leur mise en œuvre et à leur impact. Cela aidera à informer les professionnels de la santé et les gestionnaires qui prévoient de mettre en œuvre une analyse de la mortalité infantile dans leurs cadres. MÉTHODES: Les bases de données MEDLINE et EMBASE ont été recherchées pour les articles publiés entre janvier 1996 et avril 2019. Les études signalant la mise en œuvre d'un processus d'analyse de la mortalité infantile dans les PRFI ont été jugées éligibles. Une approche narrative a été utilisée pour décrire les étapes du processus d'audit décrites dans le "Guide opérationnel de l'OMS pour l'audit et l'analyse de la mortalité pédiatrique dans les établissements" qui ont été achevées, et pour synthétiser les obstacles et les facilitateurs à la mise en œuvre et à l'impact du processus d'analyse de la mortalité infantile. RÉSULTATS: Sur 776 articles potentiellement pertinents, sept études ont été incluses. Dans six études, des problèmes contribuant aux décès d'enfants et des solutions possibles ont été identifiés, dans quatre, ces solutions ont été mises en œuvre et dans une, cette mise en œuvre a été suivie. Les facteurs clés influençant la mise en œuvre et l'impact étaient: la participation aux réunions, l'utilisation d'une approche sans reproche, l'allocation de ressources humaines et financières adéquates pour apporter des changements et le niveau de l'engagement de la direction. CONCLUSIONS: Malgré l'utilisation courante des analyses de mortalité dans les services de pédiatrie, peu d'études ont été publiées sur ce sujet. La transition de l'identification des problèmes et des solutions à la mise en œuvre et au suivi des plans d'action semble être l'aspect le plus difficile du processus, qui nécessite l'engagement de ressources adéquates et un leadership fort.

Epidemiology of Chagas disease in pregnant women and congenital transmission of Trypanosoma cruzi in the Americas: systematic review and meta-analysis.

OBJECTIVE: To estimate the prevalence of Chagas disease in pregnant women and the vertical transmission of the disease. METHODS: Observational studies were identified from eight electronic databases, and details on study design, population and prevalence of Chagas disease were extracted. The data were pooled using a random-effects model, and choropleth maps were created based on geopolitical regions and countries. RESULTS: The search identified 7788 articles, of which 50 were eligible. We observed a 9% prevalence of Chagas disease among pregnant women in the Americas (95% confidence interval [CI]: 8-10, I2  = 99.96%). High disease prevalence was identified in pregnant women in South American countries (12%, 95% CI: 11-13), while lower values were identified in pregnant women in North America (2%, 95% CI: 1-3). Countries with medium Human Development Index (HDI) had a higher prevalence of Chagas disease in pregnant women (15%, 95% CI: 13-16, I2  = 99.98%) than countries with high HDI (3%, 95% CI: 2-3). The rate of vertical transmission in the continent was 2% (95% CI: 1-2). The statistical analysis showed that this heterogeneity was explained by the study design, region of the Americas and mean income of the country. CONCLUSION: South and Central American countries have a high prevalence and vertical transmission of Chagas disease. Therefore, systematic screens for this disease during the prenatal period are necessary in addition to the diagnosis and treatment of children at risk for Trypanosoma cruzi infection.

OBJECTIF: Estimer la prévalence de la maladie de Chagas chez les femmes enceintes et la transmission verticale de la maladie. MÉTHODES: Des études d'observation ont été identifiées à partir de huit bases de données électroniques et des détails sur la concept de l'étude, la population et la prévalence de la maladie de Chagas ont été extraits. Les données ont été regroupées à l'aide d'un modèle à effets aléatoires et des cartes choroplèthes ont été créées en fonction des régions et des pays géopolitiques. RÉSULTATS: La recherche a identifié 7.788 articles, dont 50 étaient éligibles. Nous avons observé une prévalence de 9% de la maladie de Chagas chez les femmes enceintes dans les Amériques (intervalle de confiance [IC] à 95%: 8-10, I2 = 99,96%). Une prévalence élevée de la maladie a été identifiée chez les femmes enceintes dans les pays d'Amérique du Sud (12%, IC95%: 11-13), tandis que des valeurs plus faibles ont été identifiées chez les femmes enceintes d'Amérique du Nord (2%, IC95%: 1-3). Les pays à indice de développement humain (IDH) moyen présentaient une prévalence plus élevée de la maladie de Chagas chez les femmes enceintes (15%, IC95%: 13-16, I2 = 99,98%) que les pays à IDH élevé (3%, IC95%: 2 -3). Le taux de transmission verticale sur le continent était de 2% (IC95%: 1-2). L'analyse statistique a montré que cette hétérogénéité s'expliquait par le concept d'étude, la région des Amériques et le revenu moyen du pays. CONCLUSION: Les pays d'Amérique du Sud et d'Amérique centrale ont une prévalence élevée et de transmission verticale de la maladie de Chagas. Par conséquent, des dépistages systématiques de cette maladie pendant la période prénatale sont nécessaires en plus du diagnostic et du traitement des enfants à risque d'infection par Trypanosoma cruzi.

Prevalence of multidrug-resistant tuberculosis in Latin America and the Caribbean: a systematic review and meta-analysis.

OBJECTIVES: To evaluate the prevalence of multidrug-resistant tuberculosis (MDR-TB) in individuals living in Latin America and the Caribbean (LAC). METHODS: We searched the MEDLINE, Embase and Literatura Latino Americana e do Caribe em Ciências da Saúde (Lilacs) databases until 08 August 2019 for all studies on the subject, without time or language restrictions. Original studies reporting the prevalence of infection with Mycobacterium tuberculosis resistant to isoniazid and rifampicin simultaneously (MDR) in LAC, the prevalence of resistance in cases with no previous treatment (new cases) and the prevalence of resistance in previously treated cases were selected. Considering the expected heterogeneity between studies, all analyses were performed using the random effects model, and heterogeneity was assessed using the I2 statistic. RESULTS: We included 91 studies from 16 countries. The estimated overall prevalence was 13.0% (95% CI 12.0-14.0%), and the heterogeneity between studies was substantial (I2  = 96.1%). In the subgroup analyses, it was observed that the prevalence of MDR-TB among new cases was 7.0% (95% CI 6.0-7.0%) and in previously treated cases was 26.0% (95% CI 24.0-28.0%). CONCLUSIONS: This review highlights multidrug resistance to antituberculosis drugs in LAC, indicating that prevention strategies have not been effective. Government institutions should invest heavily in strategies for early diagnosis and the rapid availability of effective treatments and prioritise adequate protection for health professionals. In addition, screening programmes should be adopted to prevent secondary cases.

OBJECTIFS: Evaluer la prévalence de la tuberculose multirésistante (TB-MDR) chez les personnes vivant en Amérique latine et dans les Caraïbes (ALC). MÉTHODES: Nous avons effectué des recherches dans les bases de données Medline, EMBASE et Literatura Latino Americana e do Caribe em Ciências da Saúde (Lilas) jusqu'au 08 août 2019 pour toutes les études sur le sujet, sans restriction de temps ou de langue. Des études originales faisant état de la prévalence de l'infection à Mycobacterium tuberculosis résistante à l'isoniazide et à la rifampicine simultanément (MDR) dans la région ALC, de la prévalence de la résistance dans les cas sans traitement antérieur (nouveaux cas) et de la prévalence de la résistance dans les cas précédemment traités ont été sélectionnées. Compte tenu de l'hétérogénéité attendue entre les études, toutes les analyses ont été effectuées à l' aide du modèle à effets aléatoires et l'hétérogénéité a été évaluée à l' aide de la statistique I2 . RÉSULTATS: Nous avons inclus 91 études de 16 pays. La prévalence globale était estimée à 13,0% (IC95%: 12,0%-14,0%) et l'hétérogénéité entre les études était importante (I2 = 96,1%). Dans les analyses des sous-groupes, il a été observé que la prévalence de la TB-MDR parmi les nouveaux cas était de 7,0% (IC95%: 6,0%-7,0%) et dans les cas précédemment traités de 26,0% (IC95%: 24,0%-28,0%). CONCLUSIONS: Cette revue met en évidence la multirésistance aux médicaments antituberculeux dans la région ALC, indiquant que les stratégies de prévention n'ont pas été efficaces. Les institutions gouvernementales devraient investir massivement dans les stratégies de diagnostic précoce et la disponibilité rapide de traitements efficaces et accorder la priorité à une protection adéquate pour les professionnels de la santé. De plus, des programmes de dépistage devraient être adoptés pour prévenir les cas secondaires.

Improving mental health literacy in adolescents: systematic review of supporting intervention studies.

OBJECTIVE: Mental health literacy (MHL) in adolescents is an important issue as it can lead to early detection and recognition of mental illness. The aim of this systematic review was to explore the effect of supporting interventions on improving MHL in adolescents. METHODS: Systematic literature review by searching the ScienceDirect, Scopus, PubMed, Crochrane and CINAHL databases. Seven of 1107 papers were included in the final review. RESULTS: Supporting interventions for improving MHL in adolescents could be categorised into school-based and community-based. Both types used an education stand-alone strategy or an education plus contact-based group in their programmes. To provide knowledge of mental illness to adolescents, teaching methods should be interactive and use various media such as group discussion, videos and movies. CONCLUSIONS: School-based and community-based interventions were likely to improve MHL among adolescents. However, further research with objective tool measures is needed to confirm the findings.

OBJECTIF: La littératie sur la santé mentale (LSM) chez les adolescents est un sujet important car elle peut conduire à la détection et à la reconnaissance précoces des maladies mentales. Le but de cette revue systématique était d'explorer l'effet du soutien des interventions sur l'amélioration de la LSM chez les adolescents. MÉTHODES: Analyse systématique de la littérature en recherchant dans les bases de données ScienceDirect, Scopus, PubMed, Crochrane et CINAHL. 7 des 1.107 articles ont été inclus dans l'analyse finale. RÉSULTATS: L'effet des interventions de soutien visant à améliorer la LSM chez les adolescents pourraient être classés en soit du milieu scolaire, soit communautaire. Les deux types ont utilisé une stratégie basée sur l'éducation seule ou sur l'éducation et des contacts dans leurs programmes. Fournir des connaissances de la maladie mentale aux adolescents, les méthodes d'enseignement devraient être interactifs et utiliser divers médias comme la discussion de groupe, des vidéos et des films. CONCLUSIONS: Les interventions en milieu scolaire et communautaires étaient susceptibles d'améliorer la LSM chez les adolescents. Cependant, des recherches supplémentaires avec des mesures d'outils objectives sont nécessaires pour confirmer les résultats.

[Management of child and adolescent depression in primary care: A systematic meta-review]. / Prise en charge de la dépression de l'enfant et l'adolescent en soins premiers : une métarevue systématique de la littérature.

OBJECTIVE: To develop a practical guide for the management of child and adolescent depression for general practitioners (GPs), suited to their practice frame, that can be implemented on a website aimed to help GPs to manage the main mental disorders encountered in primary care. METHOD: A systematic meta-review was performed as recommended by the PRISMA statement. Each step, articles' selection, inclusion, methodological assessment and data extraction for the narrative synthesis was independently performed by two researchers. A study protocol was registered on PROSPERO (number CRD42016042710). The databases Pubmed, Cochrane and Web of Science were explored. Each step was performed independently by two researchers following PRISMA. Meta-analyses and systematic reviews (including guidelines based on a systematic review), published between 2002 and 2015, in English or French, dealing with the therapeutic management, in primary care, of patients aged 6 to 18 years old with a major depressive disorder (MDD) were included. Grey literature was explored searching the websites of national and international health agencies, learned societies, and article references. The methodological and report qualities were assessed using the AGREE II, PRISMA checklist and R-AMSTAR grid. A narrative synthesis was performed to produce the practical guide, prioritizing data from the best evaluated articles. An expert group of GPs' and one child psychiatrist validated the guide in its final form. RESULTS: Thirty-eight studies were included: 12 recommendations, 5 systematic reviews and 21 meta-analyses. The best evaluated guideline had an AGREE-II assessment of 81%, and the best evaluated meta-analysis had an assessment of 86% for R-AMSTAR and 96% for PRISMA. The average scores of the R-AMSTAR and PRISMA assessments were 65% and 72% respectively. The average score of the AGREE II grid assessment was 57%. The data were synthesized into a practical guide for the GPs' practice, corresponding to the different consultation times. MDD diagnosis should be done on the DSM or ICD basis. The Childrens' Depression Rating Scale-revised or the Revised Beck Depression Inventory are useful in primary care for MDD appraisal in children and adolescents. For mild MDD a supportive psychotherapy and surveillance for 4 to 6 weeks is preconized in primary care. In the absence of improvement, a specific and structured psychotherapy is recommended, and the patient should be addressed to a child psychiatrist. For moderate to severe MDD, the young patient should be addressed to a specialist in child psychiatry. A psychotherapy, which can be associated with fluoxetine, especially in adolescents, is indicated with a revaluation of the pharmacological treatment between 4 to 8 weeks. A weekly follow-up by the GP is recommended during the first month, especially after the initiation of an antidepressant to assess the suicidal risk. Beyond the first month, a consultation should be scheduled every two weeks. CONCLUSION: A clinical guide was created from the best evidence-based data to help GPs in the management of child and adolescent MDD. A French-language website, aimed to assist GPs in mental disease management and available during their consultation, will be created based on the compilation of this meta-review with other similar meta-reviews.

Methotrexate exposure and risk of strongyloidiasis.

OBJECTIVE: Rheumatologic disease patients receiving immunomodulating drugs such as methotrexate (MTX) have increased infection rates. Strongyloides, a global endemic intestinal parasite, can cause significant or fatal disease in immunocompromised patients. The risk of serious Strongyloides infection with MTX dosed for rheumatologic disease is unknown. METHODS: We performed a systematic literature review searching EMBASE, Medline and Web of Science databases. All studies reporting humans exposed to MTX and tested for Strongyloides were reviewed. Exclusion criteria were bone marrow transplantation, intrathecal route and MTX exposure completed >1 year prior to clinically apparent Strongyloides disease. RESULTS: After excluding duplicates, 294 articles were reviewed. Of these, 29 cases were described in 27 papers. Twenty cases (69%) had an underlying rheumatologic or dermatologic disease, the rest had a haematologic disease. Hyperinfection or dissemination was found in 59% of cases (52% low-dose MTX; 75% high-dose MTX). Death occurred in 34% of cases (19% low-dose MTX; 75% high-dose MTX, P < 0.01). All eight patients on high-dose MTX received other immunosuppressants. Corticosteroids were taken in 18/21 patients on low-dose MTX. One of the three patients on MTX monotherapy had hyperinfection syndrome. None had disseminated Strongyloides. CONCLUSIONS: Serious Strongyloides infection can occur with low-dose MTX particularly when given with other immunosuppression. Global travel and greater awareness of rheumatologic conditions in low- to middle-income countries will increase the exposure of individuals prescribed MTX (with or without corticosteroids) to Strongyloides. Strongyloides screening and treatment should be considered for individuals receiving low-dose MTX therapy, particularly if combined with additional immunosuppression.

OBJECTIF: Les patients atteints de maladies rhumatologiques recevant des médicaments immunomodulateurs tels que le méthotrexate (MTX) présentent des taux d'infection plus élevés. Strongyloides, un parasite intestinal endémique mondial, peut causer une maladie grave ou fatale chez les patients immunodéprimés. Le risque d'infection sévère à Strongyloides sous administration de MTX pour le traitement de la maladie rhumatologique est inconnu. MÉTHODES: Nous avons effectué une revue systématique de la littérature en recherchant les bases de données EMBASE, Medline et Web of Science. Toutes les études rapportant sur des humains exposés au MTX et testés pour Strongyloides ont été passées en revue. Les critères d'exclusion étaient la greffe de moelle osseuse, la voie intrathécale et l'exposition au MTX complétée plus d'un an avant l'apparition de la maladie à Strongyloides cliniquement apparente. RÉSULTATS: Après exclusion des doublons, 294 articles ont été analysés. Parmi ceux-ci, 29 cas ont été décrits dans 27 articles. Vingt cas (69%) avaient une maladie rhumatologique ou dermatologique sous-jacente, les autres avaient une maladie hématologique. Une hyperinfection ou dissémination a été constatée dans 59% des cas (52% sous MTX à faible dose; 75% sous MTX à forte dose). La mort est survenue dans 34% des cas (19% des cas sous MTX à faible dose; 75% des cas sous MTX à forte dose, p <0,01). Tous les huit patients ayant reçu une dose élevée de MTX avaient reçu d'autres immunosuppresseurs. Des corticostéroïdes ont été administrés à 18 patients sur 21 sous MTX à faible dose. Un des trois patients sous MTX en monothérapie avait un syndrome d'hyperinfection. Aucun n'avait une infection disséminée à Strongyloides. CONCLUSIONS: Une infection sévère à Strongyloides peut survenir avec le MTX à faible dose, en particulier lorsqu'administré avec une autre immunosuppression. Les voyages à travers le monde et une plus grande sensibilisation aux conditions rhumatologiques dans les pays à revenu faible et intermédiaire augmenteront l'exposition à Strongyloides chez les individus chez qui le MTX (avec ou sans corticostéroïdes) est prescrit. Le dépistage et le traitement de Strongyloides devraient être envisagés chez les personnes recevant un traitement au MTX à faible dose, en particulier lorsqu'associé à une immunosuppression supplémentaire.