The effect of methylphenidate on response inhibition and the event-related potential of children with Attention Deficit/Hyperactivity Disorder

Children with Attention Deficit/Hyperactivity Disorder (AD/HD) appear to be deficient in inhibitory processes, as reflected in behavioural and electrophysiological measures. This study examined the effect of methylphenidate (MPH) on response inhibition in children with AD/HD. Event-related potentials (ERPs) and skin conductance level (SCL) were recorded from 18 boys with AD/HD and 18 controls while they performed a cued Go/Nogo task with 70% Go probability. All participants performed the task twice, with an hour interval between test sessions. At the beginning of this interval children with AD/HD took their normal morning dose of MPH. The AD/HD group showed lower SCL than controls pre-medication, a difference not found subsequent to the administration of MPH. While the AD/HD group made more overall errors (omission + commission) pre-medication, and continued to make more omission errors than controls post-medication, the groups became comparable on the number of commission errors, suggesting MPH ameliorates deficits in response inhibition. Children with AD/HD displayed enhanced N1 and P2 amplitudes, and reduced N2 amplitudes relative to controls. These differences were not significant post-medication, at least partly attributable to the action of MPH. This study is unusual in the concurrent examination of electrodermal and electrophysiological measures of medication effects in children with AD/HD, with the retesting of both the AD/HD and control groups allowing a more valid estimate of the effects of medication, rather than assuming that retesting does not have a substantial impact

Methylphenidate effects in attention deficit/hyperactivity disorder: electrodermal and ERP measures during a continuous performance task

Rationale: Previous research investigating the effects of stimulants, such as methylphenidate (MPH), on children with attention deficit/hyperactivity disorder (AD/HD) has rarely included autonomic measures of arousal.Objective: Our aim was to clarify the effects of MPH on central and autonomic measures in AD/HD children during a continuous performance task (CPT) using a naturalistic open-label study.Method: Thirty-six boys (18 AD/HD and 18 control) participated in a CPT over two trial periods, allowing a more valid estimate of the effects of medication, rather than assuming that retesting per se has no substantial impact. MPH was administered to the AD/HD group 1 h prior to the second trial. Errors and reaction time (RT) were recorded as measures of performance, electrodermal activity as an autonomic nervous system measure and event-related potentials (ERPs) as an index of central nervous system activity.Results: AD/HD children made more errors than controls in the first session, but no group differences were found after medication. No significant differences were observed for RT. Skin conductance level was found to be lower in AD/HD children than controls, but this difference was also ameliorated after medication. Conversely, mean skin conductance response to target stimuli was found not to differ between groups during the initial test phase but became significantly different in phase 2. ERP data showed topographic differences between groups in N1, P2, N2 and P3 at the initial test phase, which were reduced at the second test.Conclusion: Stimulant medication ameliorated some of the dysfunctions in AD/HD children, which are reflected in behavioural and ERP measures. These results, in combination with general differences in electrodermal activity, support a hypoarousal model of AD/HD, which can explain the action of MPH in these children

Acute effects of Δ9-tetrahydrocannabinol and cannabidiol on auditory mismatch negativity

Rationale: Mismatch negativity (MMN) is a candidate endophenotype for schizophrenia subserved by N-methyl-D-aspartate receptor (NMDAR) function and there is increasing evidence that prolonged cannabis use adversely affects MMN generation. Few human studies have investigated the acute effects of cannabinoids on brain-based biomarkers of NMDAR function and synaptic plasticity. Objectives: The current study investigated the acute effects of Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD) alone and in combination on the mismatch negativity (MMN). Methods: In a randomised, double-blind, crossover placebo-controlled study, 18 frequent and 18 less-frequent cannabis users underwent 5 randomised drug sessions administered via vaporiser: (1) placebo; (2) THC 8 mg; (3) CBD 400 mg; (4) THC 8 mg + CBD 4 mg [THC + CBD low]; (5) THC 12 mg + CBD 400 mg [THC + CBDhigh]. Participants completed a multifeature MMN auditory oddball paradigm with duration, frequency and intensity deviants (6% each). Results: Relative to placebo, both THC and CBD were observed to increase duration and intensity MMN amplitude in less-frequent users, and THC also increased frequency MMN in this group. The addition of low-dose CBD added to THC attenuated the effect of THC on duration and intensity MMN amplitude in less-frequent users. The same pattern of effects was observed following high-dose CBD added to THC on duration and frequency MMN in frequent users.ConclusionsThe pattern of effects following CBD combined with THC on MMN may be subserved by different underlying neurobiological interactions within the endocannabinoid system that vary as a function of prior cannabis exposure. These results highlight the complex interplay between the acute effects of exogenous cannabinoids and NMDAR function. Further research is needed to determine how this process normalises after the acute effects dissipate and following repeated acute exposure.Lisa-Marie Greenwood, Samantha J. Broyd, Hendrika H. van Hell, Juanita Todd, Alison Jones, Robin M. Murray, Rodney J. Croft, Patricia T. Michie, Nadia Solowi

Critical care usage after major gastrointestinal and liver surgery: a prospective, multicentre observational study

Background Patient selection for critical care admission must balance patient safety with optimal resource allocation. This study aimed to determine the relationship between critical care admission, and postoperative mortality after abdominal surgery. Methods This prespecified secondary analysis of a multicentre, prospective, observational study included consecutive patients enrolled in the DISCOVER study from UK and Republic of Ireland undergoing major gastrointestinal and liver surgery between October and December 2014. The primary outcome was 30-day mortality. Multivariate logistic regression was used to explore associations between critical care admission (planned and unplanned) and mortality, and inter-centre variation in critical care admission after emergency laparotomy. Results Of 4529 patients included, 37.8% (n=1713) underwent planned critical care admissions from theatre. Some 3.1% (n=86/2816) admitted to ward-level care subsequently underwent unplanned critical care admission. Overall 30-day mortality was 2.9% (n=133/4519), and the risk-adjusted association between 30-day mortality and critical care admission was higher in unplanned [odds ratio (OR): 8.65, 95% confidence interval (CI): 3.51–19.97) than planned admissions (OR: 2.32, 95% CI: 1.43–3.85). Some 26.7% of patients (n=1210/4529) underwent emergency laparotomies. After adjustment, 49.3% (95% CI: 46.8–51.9%, P<0.001) were predicted to have planned critical care admissions, with 7% (n=10/145) of centres outside the 95% CI. Conclusions After risk adjustment, no 30-day survival benefit was identified for either planned or unplanned postoperative admissions to critical care within this cohort. This likely represents appropriate admission of the highest-risk patients. Planned admissions in selected, intermediate-risk patients may present a strategy to mitigate the risk of unplanned admission. Substantial inter-centre variation exists in planned critical care admissions after emergency laparotomies

Body mass index and complications following major gastrointestinal surgery: A prospective, international cohort study and meta-analysis

Aim Previous studies reported conflicting evidence on the effects of obesity on outcomes after gastrointestinal surgery. The aims of this study were to explore the relationship of obesity with major postoperative complications in an international cohort and to present a metaanalysis of all available prospective data. Methods This prospective, multicentre study included adults undergoing both elective and emergency gastrointestinal resection, reversal of stoma or formation of stoma. The primary end-point was 30-day major complications (Clavien–Dindo Grades III–V). A systematic search was undertaken for studies assessing the relationship between obesity and major complications after gastrointestinal surgery. Individual patient meta-analysis was used to analyse pooled results. Results This study included 2519 patients across 127 centres, of whom 560 (22.2%) were obese. Unadjusted major complication rates were lower in obese vs normal weight patients (13.0% vs 16.2%, respectively), but this did not reach statistical significance (P = 0.863) on multivariate analysis for patients having surgery for either malignant or benign conditions. Individual patient meta-analysis demonstrated that obese patients undergoing surgery formalignancy were at increased risk of major complications (OR 2.10, 95% CI 1.49–2.96, P < 0.001), whereas obese patients undergoing surgery for benign indications were at decreased risk (OR 0.59, 95% CI 0.46–0.75, P < 0.001) compared to normal weight patients. Conclusions In our international data, obesity was not found to be associated with major complications following gastrointestinal surgery. Meta-analysis of available prospective data made a novel finding of obesity being associated with different outcomes depending on whether patients were undergoing surgery for benign or malignant disease