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ObjectivesTo evaluate prevention strategies, their unintended consequences and modifiable risk factors for sport-related concussion (SRC) and/or head impact risk.DesignThis systematic review and meta-analysis was registered on PROSPERO (CRD42019152982) and conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Data sourcesEight databases (MEDLINE, CINAHL, APA PsycINFO, Cochrane (Systematic Review and Controlled Trails Registry), SPORTDiscus, EMBASE, ERIC0 were searched in October 2019 and updated in March 2022, and references searched from any identified systematic review.Eligibility criteriaStudy inclusion criteria were as follows: (1) original data human research studies, (2) investigated SRC or head impacts, (3) evaluated an SRC prevention intervention, unintended consequence or modifiable risk factor, (4) participants competing in any sport, (5) analytic study design, (6) systematic reviews and meta-analyses were included to identify original data manuscripts in reference search and (7) peer-reviewed. Exclusion criteria were as follows: (1) review articles, pre-experimental, ecological, case series or case studies and (2) not written in English.ResultsIn total, 220 studies were eligible for inclusion and 192 studies were included in the results based on methodological criteria as assessed through the Scottish Intercollegiate Guidelines Network high (‘++’) or acceptable (‘+’) quality. Evidence was available examining protective gear (eg, helmets, headgear, mouthguards) (n=39), policy and rule changes (n=38), training strategies (n=34), SRC management strategies (n=12), unintended consequences (n=5) and modifiable risk factors (n=64). Meta-analyses demonstrated a protective effect of mouthguards in collision sports (incidence rate ratio, IRR 0.74; 95% CI 0.64 to 0.89). Policy disallowing bodychecking in child and adolescent ice hockey was associated with a 58% lower concussion rate compared with bodychecking leagues (IRR 0.42; 95% CI 0.33 to 0.53), and evidence supports no unintended injury consequences of policy disallowing bodychecking. In American football, strategies limiting contact in practices were associated with a 64% lower practice-related concussion rate (IRR 0.36; 95% CI 0.16 to 0.80). Some evidence also supports up to 60% lower concussion rates with implementation of a neuromuscular training warm-up programme in rugby. More research examining potentially modifiable risk factors (eg, neck strength, optimal tackle technique) are needed to inform concussion prevention strategies.ConclusionsPolicy and rule modifications, personal protective equipment, and neuromuscular training strategies may help to prevent SRC.PROSPERO registration numberCRD42019152982.

The long-term effect of regular cannabis use on brain function underlying cognitive control remains equivocal. Cognitive control abilities are thought to have a major role in everyday functioning, and their dysfunction has been implicated in the maintenance of maladaptive drug-taking patterns. In this study, the Multi-Source Interference Task was employed alongside functional magnetic resonance imaging and psychophysiological interaction methods to investigate functional interactions between brain regions underlying cognitive control. Current cannabis users with a history of greater than 10 years of daily or near-daily cannabis smoking (n=21) were compared with age, gender, and IQ-matched non-using controls (n=21). No differences in behavioral performance or magnitude of task-related brain activations were evident between the groups. However, greater connectivity between the prefrontal cortex and the occipitoparietal cortex was evident in cannabis users, as compared with controls, as cognitive control demands increased. The magnitude of this connectivity was positively associated with age of onset and lifetime exposure to cannabis. These findings suggest that brain regions responsible for coordinating behavioral control have an increased influence on the direction and switching of attention in cannabis users, and that these changes may have a compensatory role in mitigating cannabis-related impairments in cognitive control or perceptual processes.

Background General practitioners (GPs) have a key role in concussion diagnosis and management. Recent surveys have shown that GPs are competent in diagnosis but lack confidence in appropriate concussion management. Although some patients recover spontaneously, early education is valuable, and provision of evidence-informed, individualised management plans May facilitate recovery within typical recovery windows. Objectives The aim of this article is to provide GPs with contemporary recommendations on paediatric concussion diagnosis and management in the acute and subacute phases, and to highlight the benefit of a biopsychosocial approach and multidisciplinary management. Discussion Paediatric concussion management can be complex, requiring a biopsychosocial approach, including a thorough understanding of each individual paediatric patient's pre-concussion history. Given the relationship GPs have with their patients, they are well placed to coordinate multidisciplinary care. For paediatric patients who are at risk of a prolonged recovery or persisting symptoms, early identification and referral for multidisciplinary care are essential.

There is growing evidence that inhalants are neurotoxic to white matter, yet limited work has been conducted to investigate the neurobiologic effects of long-term exposure among adolescent users, despite inhalant use being most prominent during this developmental period. We used diffusion tensor imaging to examine white-matter integrity in 11 adolescents who used inhalants, 11 matched cannabis users and 8 drug-naive controls. Although both groups of drug users had white-matter abnormalities (i.e., lower fractional anisotropy), abnormalities were more pronounced in the inhalant group, particularly among early-onset users. The findings of this study should be considered in light of its small sample size, cross-sectional design and the complex psychosocial background of long-term inhalant users. White-matter abnormalities may underpin long-term behavioural and mental health problems seen in individuals with long-term inhalant use.

ObjectiveThis systematic review and meta-analysis sought to rigorously examine mental health outcomes following paediatric concussion. To date, heterogeneous findings and methodologies have limited clinicians’ and researchers’ ability to meaningfully synthesise existing literature. In this context, there is a need to clarify mental health outcomes in a homogeneous sample, controlling for key methodological differences and applying a consistent definition of concussion across studies.DesignSystematic review and meta-analysis.Data sourcesWe searched Medline, Embase, PsycINFO, CINAHL, SportDiscus, Scopus and PubMed.EligibilityPeer-reviewed studies published between 1980 and June 2020 that prospectively examined mental health outcomes after paediatric concussion, defined as per the Berlin Consensus Statement on Concussion in Sport.ResultsSixty-nine articles characterising 60 unique samples met inclusion criteria, representing 89 114 children with concussion. Forty articles (33 studies) contributed to a random effects meta-analysis of internalising (withdrawal, anxiety, depression, post-traumatic stress), externalising (conduct problems, aggression, attention, hyperactivity) and total mental health difficulties across three time points post-injury (acute, persisting and chronic). Overall, children with concussion (n=6819) experienced significantly higher levels of internalising (g=0.41–0.46), externalising (g=0.25–0.46) and overall mental health difficulties compared with controls (g=0.18–0.49; n=56 271), with effects decreasing over time.Summary/conclusionsOur review highlights that mental health is central to concussion recovery. Assessment, prevention and intervention of mental health status should be integrated into standard follow-up procedures. Further research is needed to clarify the mechanisms underlying observed relationships between mental health, post-concussion symptoms and other psychosocial factors. Results suggest that concussion may both precipitate and exacerbate mental health difficulties, thus impacting delayed recovery and psychosocial outcomes.

IntroductionWhile most children recover from a concussion shortly after injury, approximately 30% experience persistent postconcussive symptoms (pPCS) beyond 1-month postinjury. Existing research into the treatment of pPCS have evaluated unimodal approaches, despite evidence suggesting that pPCS likely represent an interaction across various symptom clusters. The primary aim of this study is to evaluate the effectiveness of a multimodal, symptom-tailored intervention to accelerate symptom recovery and increase the proportion of children with resolved symptoms at 3 months postconcussion.Methods and analysisIn this open-label, assessor-blinded, randomised clinical trial, children with concussion aged 8–18 years will be recruited from The Royal Children’s Hospital (The RCH) emergency department, or referred by a clinician, within 17 days of initial injury. Based on parent ratings of their child’s PCS at ~10 days postinjury, symptomatic children (≥2 symptoms at least 1-point above those endorsed preinjury) will undergo a baseline assessment at 3 weeks postinjury and randomised into either Concussion Essentials (CE, n=108), a multimodal, interdisciplinary delivered, symptom-tailored treatment involving physiotherapy, psychology and education, or usual care (UC, n=108) study arms. CE participants will receive 1 hour of intervention each week, for up to 8 weeks or until pPCS resolve. A postprogramme assessment will be conducted at 3 months postinjury for all participants. Effectiveness of the CE intervention will be determined by the proportion of participants for whom pPCS have resolved at the postprogramme assessment (primary outcome) relative to the UC group. Secondary outcome analyses will examine whether children receiving CE are more likely to demonstrate resolution of pPCS, earlier return to normal activity, higher quality of life and a lower rate of utilisation of health services, compared with the UC group.Ethics and disseminationEthics were approved by The RCH Human Research Ethics Committee (HREC: 37100). Parent, and for mature minors, participant consent, will be obtained prior to commencement of the trial. Study results will be disseminated at international conferences and international peer-reviewed journals.Trial registration numberACTRN12617000418370; pre-results.

Abstract Background Although attention deficit hyperactivity disorder (ADHD) is known to be common in psychotic disorders, reported prevalence rates vary widely, with limited understanding of how different factors (eg, assessment methods, geographical region) may be associated with this variation. The aim was to conduct a systematic review and meta-analysis to determine the prevalence of ADHD in psychotic disorders and factors associated with the variability in reported rates. Study Design Searches were conducted in MEDLINE, Embase, PsycINFO, CINAHL, and Scopus in May 2023. Studies were eligible if the frequency of ADHD was reported in psychotic disorder samples. Pooled prevalence meta-analyses were performed. Subgroup analyses and meta-regressions explored whether demographic and study characteristics were associated with reported rates. Study Results Thirty-six studies were included, involving 30 726 individuals. The pooled lifetime prevalence of ADHD in psychotic disorders was 18.49% (95% CI 11.78%, 27.83%). The between-study heterogeneity was high (I2 = 98.4% [95% CI 98.2%, 98.6%]). Subgroup analyses revealed higher prevalence rates when using ADHD DSM-IV criteria compared to International Classification of Diseases (ICD)-10. Rates in childhood-onset psychotic disorders were higher than adolescent- and adult-onset psychotic disorder samples. Rates were higher in North America compared to other regions. Meta-regressions indicated a decrease in prevalence rates with publication year. Conclusions The prevalence of ADHD in psychotic disorders appears higher than in the general population, highlighting the need for clinical attention and further research into this comorbidity. Reported rates, however, vary significantly. Reasons may include diagnostic criteria, age of psychosis onset, region, study design, and publication year. Future research should investigate these factors using rigorous ADHD assessment protocols.

In laboratory animals, exposure to most general anaesthetics leads to neurotoxicity manifested by neuronal cell death and abnormal behaviour and cognition. Some large human cohort studies have shown an association between general anaesthesia at a young age and subsequent neurodevelopmental deficits, but these studies are prone to bias. Others have found no evidence for an association. We aimed to establish whether general anaesthesia in early infancy affects neurodevelopmental outcomes. In this international, assessor-masked, equivalence, randomised, controlled trial conducted at 28 hospitals in Australia, Italy, the USA, the UK, Canada, the Netherlands, and New Zealand, we recruited infants of less than 60 weeks' postmenstrual age who were born at more than 26 weeks' gestation and were undergoing inguinal herniorrhaphy, without previous exposure to general anaesthesia or risk factors for neurological injury. Patients were randomly assigned (1:1) by use of a web-based randomisation service to receive either awake-regional anaesthetic or sevoflurane-based general anaesthetic. Anaesthetists were aware of group allocation, but individuals administering the neurodevelopmental assessments were not. Parents were informed of their infants group allocation upon request, but were told to mask this information from assessors. The primary outcome measure was full-scale intelligence quotient (FSIQ) on the Wechsler Preschool and Primary Scale of Intelligence, third edition (WPPSI-III), at 5 years of age. The primary analysis was done on a per-protocol basis, adjusted for gestational age at birth and country, with multiple imputation used to account for missing data. An intention-to-treat analysis was also done. A difference in means of 5 points was predefined as the clinical equivalence margin. This completed trial is registered with ANZCTR, number ACTRN12606000441516, and ClinicalTrials.gov, number NCT00756600. Between Feb 9, 2007, and Jan 31, 2013, 4023 infants were screened and 722 were randomly allocated: 363 (50%) to the awake-regional anaesthesia group and 359 (50%) to the general anaesthesia group. There were 74 protocol violations in the awake-regional anaesthesia group and two in the general anaesthesia group. Primary outcome data for the per-protocol analysis were obtained from 205 children in the awake-regional anaesthesia group and 242 in the general anaesthesia group. The median duration of general anaesthesia was 54 min (IQR 41–70). The mean FSIQ score was 99·08 (SD 18·35) in the awake-regional anaesthesia group and 98·97 (19·66) in the general anaesthesia group, with a difference in means (awake-regional anaesthesia minus general anaesthesia) of 0·23 (95% CI −2·59 to 3·06), providing strong evidence of equivalence. The results of the intention-to-treat analysis were similar to those of the per-protocol analysis. Slightly less than 1 h of general anaesthesia in early infancy does not alter neurodevelopmental outcome at age 5 years compared with awake-regional anaesthesia in a predominantly male study population. US National Institutes of Health, US Food and Drug Administration, Thrasher Research Fund, Australian National Health and Medical Research Council, Health Technologies Assessment–National Institute for Health Research (UK), Australian and New Zealand College of Anaesthetists, Murdoch Children's Research Institute, Canadian Institutes of Health Research, Canadian Anesthesiologists Society, Pfizer Canada, Italian Ministry of Health, Fonds NutsOhra, UK Clinical Research Network, Perth Children's Hospital Foundation, the Stan Perron Charitable Trust, and the Callahan Estate.

Preclinical data suggest that general anaesthetics affect brain development. There is mixed evidence from cohort studies that young children exposed to anaesthesia can have an increased risk of poor neurodevelopmental outcome. We aimed to establish whether general anaesthesia in infancy has any effect on neurodevelopmental outcome. Here we report the secondary outcome of neurodevelopmental outcome at 2 years of age in the General Anaesthesia compared to Spinal anaesthesia (GAS) trial. In this international assessor-masked randomised controlled equivalence trial, we recruited infants younger than 60 weeks postmenstrual age, born at greater than 26 weeks' gestation, and who had inguinal herniorrhaphy, from 28 hospitals in Australia, Italy, the USA, the UK, Canada, the Netherlands, and New Zealand. Infants were randomly assigned (1:1) to receive either awake-regional anaesthesia or sevoflurane-based general anaesthesia. Web-based randomisation was done in blocks of two or four and stratified by site and gestational age at birth. Infants were excluded if they had existing risk factors for neurological injury. The primary outcome of the trial will be the Wechsler Preschool and Primary Scale of Intelligence Third Edition (WPPSI-III) Full Scale Intelligence Quotient score at age 5 years. The secondary outcome, reported here, is the composite cognitive score of the Bayley Scales of Infant and Toddler Development III, assessed at 2 years. The analysis was as per protocol adjusted for gestational age at birth. A difference in means of five points (1/3 SD) was predefined as the clinical equivalence margin. This trial is registered with ANZCTR, number ACTRN12606000441516 and ClinicalTrials.gov, number NCT00756600. Between Feb 9, 2007, and Jan 31, 2013, 363 infants were randomly assigned to receive awake-regional anaesthesia and 359 to general anaesthesia. Outcome data were available for 238 children in the awake-regional group and 294 in the general anaesthesia group. In the as-per-protocol analysis, the cognitive composite score (mean [SD]) was 98·6 (14·2) in the awake-regional group and 98·2 (14·7) in the general anaesthesia group. There was equivalence in mean between groups (awake-regional minus general anaesthesia 0·169, 95% CI −2·30 to 2·64). The median duration of anaesthesia in the general anaesthesia group was 54 min. For this secondary outcome, we found no evidence that just less than 1 h of sevoflurane anaesthesia in infancy increases the risk of adverse neurodevelopmental outcome at 2 years of age compared with awake-regional anaesthesia. Australia National Health and Medical Research Council (NHMRC), Health Technologies Assessment-National Institute for Health Research UK, National Institutes of Health, Food and Drug Administration, Australian and New Zealand College of Anaesthetists, Murdoch Childrens Research Institute, Canadian Institute of Health Research, Canadian Anesthesiologists' Society, Pfizer Canada, Italian Ministry of Heath, Fonds NutsOhra, and UK Clinical Research Network (UKCRN).

Mild traumatic brain injury (mTBI)-associated blood proteomics have become an emerging focus in the past decade, with the U.S. Food and Drug Administration recently approving the use of a blood test to determine the necessity of a computed tomography scan after adult mTBI. We now also know that the blood proteome of children is different from that of adults, and new evidence suggests that children may take longer to recover from an mTBI. Despite this, comparatively fewer studies have analyzed changes in blood protein expression after pediatric mTBI. Concussions, an mTBI subset, often go underreported, despite the potential for post-concussive symptoms to last more than one month in up to 30% of children. In the current study, we used a multiplex immunoassay to measure blood protein expression of Apolipoprotein, enolase 2, glial fibrillary acidic protein, interleukin (IL)-1B, IL-6, IL-8, IL-10, S100 calcium-binding protein B, tau and tumor necrosis factor alpha (TNFα) at admission, one to four days, two weeks, and three months post-pediatric concussion, comparing patients with normal recovery (n = 9) with those with persisting symptoms (n = 9). We identified significant differences in IL-6 (p < 0.001) and tau (p = 0.048) protein expression across time post-injury irrespective of clinical outcome and in IL-8 protein expression (p = 0.041) across time post-injury specific to children with persisting symptoms. Significantly, we have identified an increase in TNFα protein expression at one to four days post-injury (p = 0.031) in children with persisting symptoms compared with normal recovery. To our knowledge, this is the first study to identify TNFα as a potential blood biomarker for persisting symptoms post-pediatric concussion.