Effects of transcranial direct current stimulation in children and young people with psychiatric disorders: a systematic review.

Transcranial direct current stimulation (tDCS) has demonstrated benefits in adults with various psychiatric disorders, but its clinical utility in children and young people (CYP) remains unclear. This PRISMA systematic review used published and ongoing studies to examine the effects of tDCS on disorder-specific symptoms, mood and neurocognition in CYP with psychiatric disorders. We searched Medline via PubMed, Embase, PsychINFO via OVID, and Clinicaltrials.gov up to December 2022. Eligible studies involved multiple session (i.e., treatment) tDCS in CYP (≤ 25 years old) with psychiatric disorders. Two independent raters assessed the eligibility of studies and extracted data using a custom-built form. Of 33 eligible studies (participant N = 517), the majority (n = 27) reported an improvement in at least one outcome measure of disorder-specific symptoms. Few studies (n = 13) examined tDCS effects on mood and/or neurocognition, but findings were mainly positive. Overall, tDCS was well tolerated with minimal side effects. Of 11 eligible ongoing studies, many are sham-controlled RCTs (n = 9) with better blinding techniques and a larger estimated participant enrolment (M = 79.7; range 15-172) than published studies. Although encouraging, the evidence to date is insufficient to firmly conclude that tDCS can improve clinical symptoms, mood, or cognition in CYP with psychiatric disorders. Ongoing studies appear of improved methodological quality; however, future studies should broaden outcome measures to more comprehensively assess the effects of tDCS and develop dosage guidance (i.e., treatment regimens). [Abstract copyright: © 2023. The Author(s).

Computerized cognitive training in attention-deficit/hyperactivity disorder (ADHD): a meta-analysis of randomized controlled trials with blinded and objective outcomes

This meta-analysis investigated the effects of computerized cognitive training (CCT) on clinical, neuropsychological and academic outcomes in individuals with attention-deficit/hyperactivity disorder (ADHD). The authors searched PubMed, Ovid, and Web of Science until 19th January 2022 for parallel-arm randomized controlled trials (RCTs) using CCT in individuals with ADHD. Random-effects meta-analyses pooled standardized mean differences (SMD) between CCT and comparator arms. RCT quality was assessed with the Cochrane Risk of Bias 2.0 tool (PROSPERO: CRD42021229279). Thirty-six RCTs were meta-analysed, 17 of which evaluated working memory training (WMT). Analysis of outcomes measured immediately post-treatment and judged to be “probably blinded” (PBLIND; trial n = 14) showed no effect on ADHD total (SMD = 0.12, 95%CI[−0.01 to −0.25]) or hyperactivity/impulsivity symptoms (SMD = 0.12, 95%[−0.03 to−0.28]). These findings remained when analyses were restricted to trials (n: 5–13) with children/adolescents, low medication exposure, semi-active controls, or WMT or multiple process training. There was a small improvement in inattention symptoms (SMD = 0.17, 95%CI[0.02–0.31]), which remained when trials were restricted to semi-active controls (SMD = 0.20, 95%CI[0.04–0.37]), and doubled in size when assessed in the intervention delivery setting (n = 5, SMD = 0.40, 95%CI[0.09–0.71]), suggesting a setting-specific effect. CCT improved WM (verbal: n = 15, SMD = 0.38, 95%CI[0.24–0.53]; visual-spatial: n = 9, SMD = 0.49, 95%CI[0.31–0.67]), but not other neuropsychological (e.g., attention, inhibition) or academic outcomes (e.g., reading, arithmetic; analysed n: 5–15). Longer-term improvement (at ~6-months) in verbal WM, reading comprehension, and ratings of executive functions were observed but relevant trials were limited in number (n: 5–7). There was no evidence that multi-process training was superior to working memory training. In sum, CCT led to shorter-term improvements in WM, with some evidence that verbal WM effects persisted in the longer-term. Clinical effects were limited to small, setting specific, short-term effects on inattention symptoms

Are Small Effects the Indispensable Foundation for a Cumulative Psychological Science? A Reply to Götz et al. (2022).

Götz et al. (2022) argue that small effects are “the indispensable foundation for a cumulative psychological science”. They support their argument by claiming that (i) psychology, like genetics, consists of complex phenomena explained by additive small effects, (ii) psychological research culture rewards large effects, which means small effects are being ignored, and (iii) small effects become meaningful at scale and over time. We rebut these claims with three objections: (i) the analogy between genetics and psychology is misleading, (ii) p-values are the main currency for publication in psychology, meaning that any biases in the literature are (currently) caused by a pressure to publish statistically significant results and not large effects, and (iii) claims regarding small effects as important and consequential must be supported by empirical evidence or, at least, a falsifiable line of reasoning. If accepted uncritically, we believe the arguments of Götz et al. (2022) could be used as a blanket justification for the importance of any and all ‘small’ effects, thereby undermining best practices in effect size interpretation. We end with guidance on evaluating effect sizes in relative, not absolute terms

Computerized cognitive training in attention-deficit/hyperactivity disorder (ADHD): a meta-analysis of randomized controlled trials with blinded and objective outcomes

This meta-analysis investigated the effects of computerized cognitive training (CCT) on clinical, neuropsychological and academic outcomes in individuals with attention-deficit/hyperactivity disorder (ADHD). The authors searched PubMed, Ovid, and Web of Science until 19th January 2022 for parallel-arm randomized controlled trials (RCTs) using CCT in individuals with ADHD. Random-effects meta-analyses pooled standardized mean differences (SMD) between CCT and comparator arms. RCT quality was assessed with the Cochrane Risk of Bias 2.0 tool (PROSPERO: CRD42021229279). Thirty-six RCTs were meta-analysed, 17 of which evaluated working memory training (WMT). Analysis of outcomes measured immediately post-treatment and judged to be “probably blinded” (PBLIND; trial n = 14) showed no effect on ADHD total (SMD = 0.12, 95%CI[−0.01 to −0.25]) or hyperactivity/impulsivity symptoms (SMD = 0.12, 95%[−0.03 to−0.28]). These findings remained when analyses were restricted to trials (n: 5–13) with children/adolescents, low medication exposure, semi-active controls, or WMT or multiple process training. There was a small improvement in inattention symptoms (SMD = 0.17, 95%CI[0.02–0.31]), which remained when trials were restricted to semi-active controls (SMD = 0.20, 95%CI[0.04–0.37]), and doubled in size when assessed in the intervention delivery setting (n = 5, SMD = 0.40, 95%CI[0.09–0.71]), suggesting a setting-specific effect. CCT improved WM (verbal: n = 15, SMD = 0.38, 95%CI[0.24–0.53]; visual-spatial: n = 9, SMD = 0.49, 95%CI[0.31–0.67]), but not other neuropsychological (e.g., attention, inhibition) or academic outcomes (e.g., reading, arithmetic; analysed n: 5–15). Longer-term improvement (at ~6-months) in verbal WM, reading comprehension, and ratings of executive functions were observed but relevant trials were limited in number (n: 5–7). There was no evidence that multi-process training was superior to working memory training. In sum, CCT led to shorter-term improvements in WM, with some evidence that verbal WM effects persisted in the longer-term. Clinical effects were limited to small, setting specific, short-term effects on inattention symptoms

Null Effects on Working Memory and Verbal Fluency Tasks When Applying Anodal tDCS to the Inferior Frontal Gyrus of Healthy Participants

Transcranial direct current stimulation (tDCS) is a technique used to modify cognition by modulating underlying cortical excitability via weak electric current applied through the scalp. Although many studies have reported positive effects with tDCS, a number of recent studies highlight that tDCS effects can be small and difficult to reproduce. This is especially the case when attempting to modulate performance using single applications of tDCS in healthy participants. Possible reasons may be that optimal stimulation parameters have yet to be identified, and that individual variation in cortical activity and/or level of ability confound outcomes. To address these points, we carried out a series of experiments in which we attempted to modulate performance in fluency and working memory probe tasks using stimulation parameters which have been associated with positive outcomes: we targeted the left inferior frontal gyrus and compared performance when applying a 1.5mA anodal current for 25 mins and with sham stimulation. There is evidence that LIFG plays a role in these tasks and previous studies have found positive effects of stimulation. We also compared our experimental group (N=19-20) with a control group receiving no stimulation (n = 24). More importantly, we also considered effects on subgroups subdivided according to memory span as well as to more direct measures of executive function abilities and motivational levels. We found no systematic effect of stimulation. Our findings are in line with a growing body of evidence that tDCS produces unreliable effects. We acknowledge that our findings speak to the conditions we investigated, and that alternative protocols (e.g., multiple sessions, clinical samples, and different stimulation polarities) may be more effective. We encourage further research to explore optimal conditions for tDCS efficacy, given the potential benefits that this technique poses for understanding and enhancing cognition

Risk of bowel obstruction in patients with colon cancer responding to immunotherapy: an international case series

Background Immunotherapy is used routinely for treating deficient mismatch repair (dMMR) colon cancer (CC). This case series highlights an emerging safety issue, where patients develop bowel obstruction associated with immunotherapy response. Patients and methods Patients with dMMR CC who developed bowel obstruction while responding to immunotherapy were retrospectively identified. Data on patient, disease, treatment, and response-specific factors were explored for potential risk factors. Overall treatment numbers were used to estimate incidence. Results Nine patients from eight European centres were included. Common features were hepatic flexure location (5/9), T4 radiological staging (6/9), annular shape (8/9), radiological stricturing (5/9), and endoscopic obstruction (6/9). All received pembrolizumab and obstructed between 45 and 652 days after starting treatment. Seven patients underwent surgical resection; one was managed with a defunctioning stoma; and one was managed conservatively. One patient died from obstruction. Radiological response was seen in eight patients, including two complete responses. Pathological response was seen in all seven who underwent resection, including four complete responses. The overall incidence of immunotherapy response-related obstruction in these centres was 1.51%. Conclusions Bowel obstruction associated with immunotherapy response may represent a rare treatment-related complication in dMMR CC. Clinicians must recognise this safety signal and share experience to maintain patient safety

Inflammatory biomarkers in Alzheimer's disease plasma.

INTRODUCTION: Plasma biomarkers for Alzheimer's disease (AD) diagnosis/stratification are a "Holy Grail" of AD research and intensively sought; however, there are no well-established plasma markers. METHODS: A hypothesis-led plasma biomarker search was conducted in the context of international multicenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL; 259), mild cognitive impairment (MCI; 199), and AD (262) subjects from AddNeuroMed. RESULTS: Ten analytes showed significant intergroup differences. Logistic regression identified five (FB, FH, sCR1, MCP-1, eotaxin-1) that, age/APOε4 adjusted, optimally differentiated AD and CTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1) that optimally differentiated AD and MCI (AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Two analytes (FB, FH) plus age predicted MCI progression to AD (AUC: 0.71). DISCUSSION: Plasma markers of inflammation and complement dysregulation support diagnosis and outcome prediction in AD and MCI. Further replication is needed before clinical translation