The priming effect of repetitive transcranial magnetic stimulation on clinical response to electroconvulsive therapy in treatment-resistant depression: a randomized, double-blind, sham-controlled study.

BACKGROUND: Electroconvulsive therapy (ECT) is one of the most effective treatments for treatment-resistant depression (TRD). However, due to response delay and cognitive impairment, ECT remains an imperfect treatment. Compared to ECT, repetitive transcranial magnetic stimulation (rTMS) is less effective at treating severe depression, but has the advantage of being quick, easy to use, and producing almost no side effects. In this study, our objective was to assess the priming effect of rTMS sessions before ECT on clinical response in patients with TRD. METHODS: In this multicenter, randomized, double-blind, sham-controlled trial, 56 patients with TRD were assigned to active or sham rTMS before ECT treatment. Five sessions of active/sham neuronavigated rTMS were administered over the left dorsolateral prefrontal cortex (20 Hz, 90% resting motor threshold, 20 2 s trains with 60-s intervals, 800 pulses/session) before ECT (which was active for all patients) started. Any relative improvements were then compared between both groups after five ECT sessions, in order to assess the early response to treatment. RESULTS: After ECT, the active rTMS group exhibited a significantly greater relative improvement than the sham group [43.4% (28.6%) v. 25.4% (17.2%)]. The responder rate in the active group was at least three times higher. Cognitive complaints, which were assessed using the Cognitive Failures Questionnaire, were higher in the sham rTMS group compared to the active rTMS group, but this difference was not corroborated by cognitive tests. CONCLUSIONS: rTMS could be used to enhance the efficacy of ECT in patients with TRD. ClinicalTrials.gov: NCT02830399.

Critical appraisal of international guidelines for the management of Helicobacter pylori infection in case of dyspepsia.

BACKGROUND: Affecting between 20% and 90% of the world's population depending on the geo-socio-economic conditions, Helicobacter pylori (Hp) infection requires an adapted management because of the medico-economic stakes it generates. Also responsible for dyspepsia, the management of Hp infection differs in this context between international guidelines. OBJECTIVES: The primary outcome of the study was assessing the quality of current guidelines for HP eradication in dyspepsia. The secondary was defining the best therapeutic strategy for patients consulting with dyspepsia in the outpatient setting. METHODS: Clinical practice guidelines (CPG) published between January 2000 and May 2021 were retrieved from various databases (PubMed; Guidelines International Network; websites of scientific societies that issued the guidelines). Their quality was assessed using the AGREE II evaluation grid. To provide decision support for healthcare practitioners, particularly in primary care, a summary of the main points of interest for management was made for each guideline. RESULTS: Fourteen guidelines were included. Only four (28.6%) could be validated according to AGREE II? Most of the non-validated guidelines had low ratings in the "Rigour of development" and "Applicability" domains with means of 40% [8%-71%] and 14% [0%-25%], respectively. Three out of four validated guidelines (75%) advocated a "test and treat" strategy for dyspepsia based on the national prevalence of Hp. Gastroscopy was the 1st line examination method in case of warning signs or high risk of gastric cancer. Triple therapy (Proton pomp inhibitor, amoxicillin, and clarithromycin) was favored for Hp eradication but required a study of the sensitivity to clarithromycin in the validated guidelines. Antibiotic resistance also had an impact on treatment duration. CONCLUSIONS: Many guidelines were of poor quality, providing few decision-making tools for practical use. Conversely, those of good quality had established a management strategy addressing the current problems associated with the emergence of antibiotic-resistant strains.

A critical appraisal of acute sore throat guidelines using the AGREE II instrument: a scoping review.

BACKGROUND: Conflicting international guidelines exist on the management of sore throat by antibiotics. OBJECTIVES: To assess with the Appraisal of Guidelines for Research and Evaluation II (AGREE) instrument the quality of guidelines for uncomplicated acute group A beta-haemolytic streptococcal (GABHS) sore-throat. To make a sensitivity analysis restricted to guidelines with a rigour of development score higher than 60% and to describe their recommendations on scores, tests, and antibiotic therapy, including their justification. METHODS: A guideline literature review of acute GABHS sore throat, published between January 2000 and December 2019 in primary care and secondary care. The PubMed database, the Canadian Medical Association Infobase on Clinical Practice Guidelines and the International Network Guidelines were used. The quality of guidelines was assessed using the AGREE II instrument. The guidelines were classified into 2 categories: high-quality guidelines had to rate >60% for the rigour of development score, the others were classified as low-quality guidelines. RESULTS: Significant heterogeneity between the 15 guidelines concerned the scores of the 6 assessment domains. Among them, 6 guidelines presented a score above 60% with regards to the rigor of development domain and used a systematic literature search method, citing meta-analyses of recent randomised clinical trials. Most of the 6 high-quality guidelines no longer recommended the systematic use of diagnostic scores and tests, nor antibiotic therapy to prevent acute rheumatic fever or loco-regional complications, except for high-risk patients. CONCLUSION: Major discrepancies emphasise the need for only high-quality guidelines, based on adequately assessed evidence. Restricted antibiotic prescriptions to severe cases or high-risk patients would avoid antibiotic resistance.

No mercy for victims: Exploring the link between dark personality traits, aggressive video game behavior, and severe traffic violations.

This study investigates the relationship between dark personality traits, aggressive behavior in violent video games, and severe traffic violations among 200 driving offenders from Tehran, Iran, participating in a rehabilitation program. Participants engaged in a computerized shooting decision task, where their tendency to shoot unarmed targets (innocent victims), compared to armed targets (criminals), was used as an indicator of aggressive behavior toward innocent victims. Additionally, they completed self-report measures of narcissism, Machiavellianism, psychopathy, and sadism to evaluate the impact of Dark Tetrad personality traits on their behavior. Bivariate analyses revealed associations between Dark Tetrad personality traits and aggressive behavior in the video game with serious traffic offenses. Multivariate analyses identified Machiavellianism, sadism, and aggressive behavior in video games as significant predictors of severe traffic offenses. The results suggest that dark personality traits and aggressive behavior in video games may aid in better identifying road traffic offenders with the most severe violations. Potential implications for preventing repeated traffic offenses by tailoring rehabilitation programs are discussed.

How do they add up? The interaction between the placebo and treatment effect: A systematic review.

AIM: The placebo effect and the specific effect are often thought to add up (additive model). Whether additivity holds can dramatically influence the external validity of a trial. This assumption of additivity was tested by Kleijnen et al in 1994 but the data produced since then have not been synthetized. In this review, we aimed to systematically review the literature to determine whether additivity held. METHODS: We searched Medline and PsychInfo up to 10 January 2019. Studies using the balanced placebo design (BPD), testing two different strengths of placebos, were included. The presence of interaction was evaluated by comparing each group in the BPD with analysis of variance or covariance. RESULTS: Thirty studies were included and the overall risk of bias was high: four found evidence of additivity and 16 studies found evidence of interaction (seven had evidence of positive additivity). CONCLUSION: Evidence of additivity between placebo and specific features of treatments was rare in included studies. We suggest interventions for placebo-sensitive ailments should be tested in trials designed to take interactions seriously once an exploratory RCTs has proven their efficacy with sufficient internal validity.

Distinct Whole-Body Movements in Response to Alcohol and Sexual Content in Alcohol Use Disorder.

BACKGROUND: Spontaneous motor responses of approach and avoidance toward stimuli are important in characterizing psychopathological conditions, including alcohol use disorder (AUD). However, divergent results have been reported, possibly due to confounded parameters (e.g., using a symbolic vs. a sensorimotor task, implementation of approach-avoidance as a measure vs. a manipulation). METHODS: We studied whole-body/posturometric changes by using a sensorimotor measure relying on embodied cognition principles to assess forward (approach) and backward (avoidance) spontaneous leaning movements. Over a 12-second period, 51 male patients with AUD and 29 male control participants were instructed to stand still in response to both alcohol and sexual visual content. Patients with AUD were then divided into "abstainers" and "relapsers," depending on their continuous abstinence at 2 weeks postdischarge (obtained via a telephone follow-up interview). The effects of the group, the stimulus type, the experimental period, and their interactions on the posturometric changes were tested using mixed Analyses of variance (ANOVAs), with a significance threshold set at 0.05. RESULTS: Contrary to our expectations, patients and controls did not show significant difference in their forward/backward micromovements while passively viewing alcohol or sexual content (p > 0.1). However, in line with our hypothesis, patients who relapsed several weeks following discharge from the rehabilitation program were significantly more reactive and more likely to lean back during the first seconds of viewing alcohol cues (p = 0.002). Further, "relapsers" were more likely to lean forward during exposure to sexual content than participants who remained abstinent (p < 0.001). CONCLUSIONS: Among individuals with AUD, there are distinct pattern of spontaneous movements that differentiate "abstainers" and "relapsers," findings that can be understood in light of existing data and theories on action tendencies.

Inhibitory control of threat remembering in PTSD.

Intrusive traumatic recollections suggest an inability in Posttraumatic Stress Disorder (PTSD) to control and notably to inhibit memories for trauma-related information. Supported by inhibitory deficits found on experimental settings in PTSD, memory functioning and memory biases in the disorder were usually explained through inhibitory and control deficits in the processing of trauma-related information. The present study aimed to directly assess this hypothesis by investigating memory control abilities for emotional information in PTSD. For this purpose, 34 patients diagnosed with PTSD were compared to 37 non-PTSD controls on an item-cued directed forgetting paradigm for emotional words combined with a Remember/Know recognition procedure. Results revealed enhanced amounts of Remember recognitions for trauma-related words in PTSD. Moreover, we replicated findings of memory control impairments in the disorder. However, such impairments only occurred for non-trauma-related words. Accordingly, it appeared that PTSD patients presented preserved memory control abilities for trauma-related words, at the expenses of other emotional valences. Surprisingly, PTSD patients presented a preserved ability to control and notably to inhibit their memory functioning for trauma-related material. In addition to potential theoretical and clinical relevance, these results are discussed in the light of resource reallocation hypotheses and vigilant-avoidant theories of information processing in PTSD.

fMRI capture of auditory hallucinations: Validation of the two-steps method.

Our purpose was to validate a reliable method to capture brain activity concomitant with hallucinatory events, which constitute frequent and disabling experiences in schizophrenia. Capturing hallucinations using functional magnetic resonance imaging (fMRI) remains very challenging. We previously developed a method based on a two-steps strategy including (1) multivariate data-driven analysis of per-hallucinatory fMRI recording and (2) selection of the components of interest based on a post-fMRI interview. However, two tests still need to be conducted to rule out critical pitfalls of conventional fMRI capture methods before this two-steps strategy can be adopted in hallucination research: replication of these findings on an independent sample and assessment of the reliability of the hallucination-related patterns at the subject level. To do so, we recruited a sample of 45 schizophrenia patients suffering from frequent hallucinations, 20 schizophrenia patients without hallucinations and 20 matched healthy volunteers; all participants underwent four different experiments. The main findings are (1) high accuracy in reporting unexpected sensory stimuli in an MRI setting; (2) good detection concordance between hypothesis-driven and data-driven analysis methods (as used in the two-steps strategy) when controlled unexpected sensory stimuli are presented; (3) good agreement of the two-steps method with the online button-press approach to capture hallucinatory events; (4) high spatial consistency of hallucinatory-related networks detected using the two-steps method on two independent samples. By validating the two-steps method, we advance toward the possible transfer of such technology to new image-based therapies for hallucinations. Hum Brain Mapp 38:4966-4979, 2017. © 2017 Wiley Periodicals, Inc.

Therapeutic Effects of Tamsulosin in Nightmare Disorder: A Randomized, Double Blind, Placebo-Controlled, Cross-Over, Pilot Study.

Nightmare disorder is associated with functional impairment, distress, and low quality of life; however, studies on pharmacotherapy of this debilitating disorder yielded mixed results. Prazosin, a non-selective α1 blocker is reported to be effective in treatment of post-traumatic stress disorder-related nightmares. We aimed at investigating therapeutic effects of tamsulosin which has higher affinity for blocking α1A and α1D adrenoceptors in treatment of nightmare disorder. A randomized, double blind, cross-over, placebo-controlled pilot study was conducted. Patients were randomly assigned to receive Tamsulosin 0.4 mg once daily or placebo for period of four weeks. Following a 2-week wash-out period, they were crossed over to the other group and received drug or placebo for duration of 4 additional weeks. Nightmare frequency and intensity measurements were carried out using Disturbing Dreams and Nightmares Severity Index (DDNSI). Blood pressure measurements were also performed. According to per protocol analysis, mean DDNSI scores decreased following administration of tamsulosin and a statistical trend towards significance was reported (p=0.065, d=0.236). Results of intention to treat analysis showed significant difference in DDNSI scores after drug use (p=0.030, d=0.651). Additionally, DDNSI scores dropped significantly following placebo use. However, intention to treat analysis showed no statistically significant difference pre and post placebo period (0.064, d=0.040). Tamsulosin may be effective in treatment of nightmare disorder. However, further larger clinical trials are recommended to clarify the effectiveness of tamsulosin and α1 subtypes in pharmacotherapy of nightmares.

Advances in the research of melatonin in autism spectrum disorders: literature review and new perspectives.

Abnormalities in melatonin physiology may be involved or closely linked to the pathophysiology and behavioral expression of autistic disorder, given its role in neurodevelopment and reports of sleep-wake rhythm disturbances, decreased nocturnal melatonin production, and beneficial therapeutic effects of melatonin in individuals with autism. In addition, melatonin, as a pineal gland hormone produced from serotonin, is of special interest in autistic disorder given reported alterations in central and peripheral serotonin neurobiology. More specifically, the role of melatonin in the ontogenetic establishment of circadian rhythms and the synchronization of peripheral oscillators opens interesting perspectives to ascertain better the mechanisms underlying the significant relationship found between lower nocturnal melatonin excretion and increased severity of autistic social communication impairments, especially for verbal communication and social imitative play. In this article, first we review the studies on melatonin levels and the treatment studies of melatonin in autistic disorder. Then, we discuss the relationships between melatonin and autistic behavioral impairments with regard to social communication (verbal and non-verbal communication, social interaction), and repetitive behaviors or interests with difficulties adapting to change. In conclusion, we emphasize that randomized clinical trials in autism spectrum disorders are warranted to establish potential therapeutic efficacy of melatonin for social communication impairments and stereotyped behaviors or interests.