ω-3 LCPUFA supplementation during pregnancy and risk of allergic outcomes or sensitization in offspring: A systematic review and meta-analysis.

BACKGROUND: Allergic diseases have increased worldwide in the last 2 decades, with children suffering the highest burden of the condition. The ω-3 long-chain poly-unsaturated fatty acid (LCPUFA) possesses anti-inflammatory properties that could lead to a reduction in inflammatory mediators in allergies. OBJECTIVE: A systematic review and meta-analysis of the most recent follow-ups of randomized clinical trials (RCTs) was conducted to assess the effectiveness of ω-3 LCPUFA supplementation started during pregnancy on allergic outcomes in offspring. METHODS: The RCTs with a minimum of 1-month follow-up post gestation were eligible for inclusion. The CENTRAL, MEDLINE, SCOPUS, WHO's International Clinical Trials Register, E-theses, and Web of Science databases were searched. Study quality was evaluated using the Cochrane Collaboration's risk of bias tool. RESULTS: Ten RCTs (3,637 children), from 9 unique trials, examined the effectiveness of ω-3 LCPUFA supplementation started during pregnancy on the development of allergic outcomes in offspring. Heterogeneities were seen between the trials in terms of their sample, type, and duration of intervention and follow-up. Pooled estimates showed a significant reduction in childhood "sensitization to egg" (relative risk [RR] = 0.54, 95% confidence interval [CI] = 0.32-0.90), and "sensitization to peanut" (RR = 0.62, 95% CI = 0.40-0.96). No statistical differences were found for other allergic outcomes (eg, eczema, asthma/wheeze). CONCLUSION: These results suggest that intake of ω-3 LCPUFA started during pregnancy can reduce the risk of sensitization to egg and peanut; however, the evidence is limited because of the small number of studies that contributed to the meta-analyses. The current evidence on the association between supplementation with ω-3 LCPUFA started during pregnancy and allergic outcomes is weak, because of the risk of bias and heterogeneities between studies.

Comparing physician associates and foundation year 1 doctors-in-training undertaking emergency medicine consultations in England: a quantitative study of outcomes.

OBJECTIVES: To compare the contribution of physician associates (PAs) to the outcomes of emergency medicine consultations with that of foundation year 1 doctors-in-training (FY1s). DESIGN: A quantitative study using retrospective chart review of adult patients seen by PAs or FY1s from August 2018 to January 2020 using 16 months of anonymised clinical record data. SETTING: One emergency department (ED) in England. PARTICIPANTS: The outcomes of 7405 patients seen by 11 PAs and 7 FY1s were recorded, with n=4580 PAs and n=2825 FY1s having complete records. OUTCOME MEASURES: The study aimed to evaluate wait times to consultation as the primary outcome. Secondary outcomes included length of stay (LOS), patients leaving without being seen (LWBS) and unplanned returns to the ED within 72 hours with the same complaint. RESULTS: PAs working in an ED in England treated patients mainly in Majors and Resus and saw more patients out of hours compared with FY1s. Following adjustments for confounding factors, there was no significant difference in wait times to consultation between those PAs or FY1s patients (116 min vs 109 min, respectively, p=0.84). Patients seen by PAs versus FY1s had a significantly longer LOS (52 min); 237 min vs 185 min, p<0.001 (95% CI 45.03 to 59.67). LWBS rates (n=89; 1.94% for PAs vs n=34; 1.2% for FY1s) showed no significant difference (p=0.073). Unplanned reattendance rates patients within 72 hours with the same presenting complaint showed no difference between PAs and FY1s (n=261 (5.70%) vs n=128 (4.58%), respectively, p=0.167). CONCLUSION: PAs working in an ED in England managed patients with a range of conditions with a similar level of impact on three emergency medicine outcome measures as FY1s (wait times to consultation, numbers of patients LWBS or returning within 72 hours with the same presenting complaint). However, patients seen by PAs had a longer LOS.

Correction to: The contribution of physician associates or assistants to the emergency department: A systematic scoping review.

[This corrects the article DOI: 10.1002/emp2.12989.].

The contribution of physician associates or assistants to the emergency department: A systematic scoping review.

Background: New health care professionals, such as the physician associate or assistant (PA), have expanded the ability of health systems to meet the needs of the population in both primary and secondary health care settings. Although PAs are widely deployed in the emergency department (ED), their role in the ED has not previously been formally described. This systematic scoping review synthesizes and critically analyzes existing literature on the impact and perception of the role of PAs working in the ED. Methods: We performed a systematic scoping review. We searched Medline, PubMed, Scopus, PsycINFO, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Excerpta Medica Database (EMBASE) and EMCare for English language peer-reviewed studies describing PA roles in the ED. Both qualitative and quantitative studies were included. We assessed the quality of the articles using QualSyst and the mixed methods appraisal tool. Themes regarding PA roles in the ED were identified. Results: We included a total of 31 studies. Themes identified in the review included perceptions of the PA, wait times, acuity of patients seen, length of stay, those leaving without being seen (LWBS), clinical outcomes, pre-admission rates, well-being and scope of practice. Both the doctors' and patients' perception of PAs in the ED were generally high. The hindrance of them not being able to prescribe was evident. Studies showed a reduction in waiting times, length of stay, readmission rates, and those leaving without being seen when PAs work in the ED seeing moderate- to low-acuity patients. Evidence shows that PAs have a positive impact and the perceptions of the PAs are high in international EDs. There is significant evidence of PAs being key members of the health care team. Their work is particularly helpful for low- to moderate-acuity patients. With the increase in health care demand and a suffering UK National Health Service (NHS), the evidence synthesized in this review supports the potential positive impact PAs can have on the NHS and more specifically, the improvements of ED throughput metrics. Conclusions: This review identified the roles and positive influence of PAs in the ED. These findings highlight current and future challenges for PAs in the ED.

Minor neurological signs and behavioural function at age 2 years in neonatal hypoxic ischaemic encephalopathy (HIE).

BACKGROUND: Neurodevelopmental follow-up in Neonatal Hypoxic Ischaemic Encephalopathy (HIE) typically focusses on major neuromotor (cerebral palsy, CP) and severe cognitive impairment. Outcomes in those without major neuromotor impairment are less well explored. OBJECTIVES: To examine behavioural, cognitive and neurological outcomes after neonatal HIE, in a clinical cohort of children without CP, at age 2 years. METHODS: Clinical routine outcome data from children admitted to a tertiary centre with neonatal HIE for hypothermia treatment between 05/08/09-30/05/2016. Children were assessed for neuromotor status - particularly minor neurological signs (MNS), with Bayley Scales of Infant and Toddler Development III (Bayley III) or Ages and Stages Questionnaire-3 (ASQ), Child Behavior Checklist 1.5-5 (CBCL), Quantitative Checklist for Autism in Toddlers (Q-CHAT). RESULTS: Of 107 children, 75.5% had normal neurology, 12.1% CP, 12.1% MNS. Children with CP were excluded from analyses. For those without CP, Bayley-III scores were in the average range for the majority; mild cognitive delay observed in 5%, 4.2% language, 1.3% motor development; severe delay in 1.3% for cognitive, 4.2% for language. More than in the normative population scored in clinical ranges for CBCL externalising, sleep, and other problems. No significant difference was seen for Q-CHAT. Children with MNS were significantly more likely to have impaired Bayley-III scores, parent-reported internalising, sleep, and other problems. CONCLUSIONS: In this clinical cohort, the majority of children had favourable outcome at 2 years. However, children with MNS were at risk for cognitive and behavioural difficulties and will benefit from enhanced clinical follow-up and support.

Default-mode brain dysfunction in mental disorders: a systematic review.

In this review we are concerned specifically with the putative role of the default-mode network (DMN) in the pathophysiology of mental disorders. First, we define the DMN concept with regard to its neuro-anatomy, its functional organisation through low frequency neuronal oscillations, its relation to other recently discovered low frequency resting state networks, and the cognitive functions it is thought to serve. Second, we introduce methodological and analytical issues and challenges. Third, we describe putative mechanisms proposed to link DMN abnormalities and mental disorders. These include interference by network activity during task performance, altered patterns of antagonism between task specific and non-specific elements, altered connectively and integrity of the DMN, and altered psychological functions served by the network DMN. Fourth, we review the empirical literature systematically. We relate DMN dysfunction to dementia, schizophrenia, epilepsy, anxiety and depression, autism and attention deficit/hyperactivity disorder drawing out common and unique elements of the disorders. Finally, we provide an integrative overview and highlight important challenges and tasks for future research.

Prenatal Intake of Vitamins and Allergic Outcomes in the Offspring: A Systematic Review and Meta-Analysis.

BACKGROUND: Allergic diseases have seen a rise worldwide, with children suffering the highest burden. Thus, early prevention of allergic diseases is a public health priority. OBJECTIVE: To synthesize the evidence from randomized controlled trials (RCTs) assessing the effect of vitamin interventions during pregnancy on developing allergic diseases in offspring. METHODS: We searched CENTRAL, MEDLINE, SCOPUS, World Health Organization's International Clinical Trials Registration, E-theses, and Web of Science. Study quality was evaluated using Cochrane's risk of bias tool. Included RCTs had a minimum of 1-month follow-up postgestation. RESULTS: A total of 5 RCTs met the inclusion criteria, including 2456 children who used vitamins C + E (1 study), vitamin C (1 study), and vitamin D (3 studies) compared with placebo/control. Two studies were judged to have a high risk of bias for performance bias or a high rate of loss to follow-up. All were rated as low risk of bias for blinding of outcome assessment. We did not perform meta-analysis with vitamin C or vitamin C + E studies due to high heterogeneity between the 2 included studies. However, we did conduct a meta-analysis with trials on vitamin D (including 1493 children) and the results showed an association between the prenatal intake of vitamin D and the risk of developing recurrent wheeze in offspring (relative risk (RR), 0.812; 95% CI, 0.67-0.98). CONCLUSIONS: The current evidence suggests that prenatal supplementation of vitamin D might have a beneficial effect on recurrent wheezing in children. Longer-term follow-up of these studies is needed to ascertain whether this observed effect is sustained. There is lack of evidence on the effect of other vitamins for the prevention of respiratory and/or allergic outcomes.

Different effects of adding white noise on cognitive performance of sub-, normal and super-attentive school children.

OBJECTIVES: Noise often has detrimental effects on performance. However, because of the phenomenon of stochastic resonance (SR), auditory white noise (WN) can alter the "signal to noise" ratio and improve performance. The Moderate Brain Arousal (MBA) model postulates different levels of internal "neural noise" in individuals with different attentional capacities. This in turn determines the particular WN level most beneficial in each individual case-with one level of WN facilitating poor attenders but hindering super-attentive children. The objective of the present study is to find out if added WN affects cognitive performance differently in children that differ in attention ability. METHODS: Participants were teacher-rated super- (N = 25); normal- (N = 29) and sub-attentive (N = 36) children (aged 8 to 10 years). Two non-executive function (EF) tasks (a verbal episodic recall task and a delayed verbal recognition task) and two EF tasks (a visuo-spatial working memory test and a Go-NoGo task) were performed under three WN levels. The non-WN condition was only used to control for potential differences in background noise in the group testing situations. RESULTS: There were different effects of WN on performance in the three groups-adding moderate WN worsened the performance of super-attentive children for both task types and improved EF performance in sub-attentive children. The normal-attentive children's performance was unaffected by WN exposure. The shift from moderate to high levels of WN had little further effect on performance in any group. SIGNIFICANCE: The predicted differential effect of WN on performance was confirmed. However, the failure to find evidence for an inverted U function challenges current theories. Alternative explanations are discussed. We propose that WN therapy should be further investigated as a possible non-pharmacological treatment for inattention.

"Can waiting awaken the resting brain?" A comparison of waiting- and cognitive task-induced attenuation of very low frequency neural oscillations.

The default mode network (DMN) is characterised by coherent very low frequency (VLF) neural oscillations in the resting brain. The attenuation of this activity has been demonstrated following the transition from rest to performance of a broad range of cognitive goal-directed tasks. Whether the activity of resting state VLF oscillations is attenuated during non-cognitive goal-directed tasks such as waiting for rewarding outcomes is not known. This study examined the VLF EEG power from resting to performance of attention demanding task and two types of goal-directed waiting tasks. The association between the attenuation of VLF EEG power and Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms was examined. Direct current EEG (DC-EEG) data were collected from 32 healthy young adults (half high and half low ADHD symptom scorers) during (i) a rest state, (ii) while performing a cognitive demanding reaction time task (2CRT), and (iii) while undertaking each of two different goal-directed waiting conditions: "forced-to-wait (FW)" and "choose-to-wait (CW)" tasks. The spatial distribution of VLF EEG power across scalp was similar to that seen in previous resting VLF EEG studies. Significant rest-to-task attenuation of VLF EEG power occurred during the 2CRT and the CW task, but not during the FW task. The association between self-ratings of ADHD symptoms and waiting-induced attenuation was not significant. This study suggests VLF EEG power attenuation that occurs following rest-to-task transition is not simply determined by changes in cognitive load. The goal-directed nature of a task, its motivated nature and/or the involvement of effortful attention may also contribute. Future studies should explore the attenuation of resting state VLF oscillations during waiting and impulsive choice.

An electrophysiological monetary incentive delay (e-MID) task: a way to decompose the different components of neural response to positive and negative monetary reinforcement.

BACKGROUND: The ability to anticipate and then secure future rewards and avoid future punishments by responding effectively to environmental demands is at the core of successful decision making. Disruptions to these processes have been shown to be implicated in a number of psychiatric conditions. In the current paper we use the electrophysiological monetary incentive delay task (e-MID) to decompose the neural response to (i) reinforcement anticipation, (ii) reinforcement-contingent target processing and (iii) reinforcement-related feedback. METHODS: Thirty-eight adolescents and young adults performed an ERP-based analogue of the monetary incentive delay task. ERP components previously associated with motivationally salient cue (cue-P3 and contingent negative variation, CNV), target (P3) and feedback (success vs. failure; feedback-related negativity; FRN and the late positive potential; LPP) stimuli were examined. RESULTS: Response times were shorter and less variable in the monetary gain and loss conditions. Distinctive ERP components were observed for each phase of reinforcement processing. First, cue-P3 was enhanced to monetary gain cues. Predicted alterations in cue-P3 following monetary loss cues and the CNV following cues of either monetary loss or gain were not observed. Target P3 was enhanced in both incentive conditions. The FRN was greater following monetary loss feedback. LPP amplitude was enhanced following feedback denoting monetary gain and the avoidance of monetary loss. CONCLUSION: Although behaviourally the effects of monetary loss and gain were similar, the e-MID task differentiated neural processing in terms of anticipation and feedback-related brain potentials. The e-MID task and the results of the current study provide a valuable complement to fMRI-based approaches to studying normal and abnormal brain correlates of reinforcement processing.

Electrophysiological markers of the motivational salience of delay imposition and escape.

BACKGROUND: The ubiquitous tendency to choose immediate over delayed rewards can, in extremis, lead to maladaptive preferences for smaller sooner over larger later rewards (i.e., impulsive choice) in certain pathological groups. The delay aversion hypothesis provides one possible account of impulsive choice and argues that this tendency is motivated by the avoidance of the negative affective states associated with delay imposed prior to the delivery of a large reward. This model also predicts that on non-choice tasks individuals will be motivated to work harder and more efficiently, when given the opportunity to avoid delay. In the current paper we studied the neural markers of the motivational salience of the imposition and escape from delay using a simple reaction time task under two conditions: First where fast responses were expected to lead to delay escape and second where delay was inescapable. METHODS: Forty participants performed the Escape Delay Incentive (EDI) task during which they were asked to respond as quickly as they could to a target stimulus. The EDI task included two conditions: first, a Delay Escape condition where fast responses led to the avoidance of delay and a Delay No-Escape condition in which a delay was presented on every trial irrespective of response speed. EEG was recorded from 66 equidistant electrode sites across the scalp. The neural response in these two conditions was compared in terms of contingent negative variation (CNV; preparation of motivated responses) and late positive potential, LPP; evaluation of performance feedback). RESULTS: As predicted individuals responded more quickly and showed enhanced CNV amplitude to Delay Escape compared with Delay No-Escape trials. Enhanced LPP amplitude was also observed when participants were not able to avoid the delay in the Delay Escape condition. ADHD symptoms were associated with larger CNV differences between Delay Escape and Delay No-Escape conditions. An association between ADHD symptoms and the LPP in the Delay Escape condition did not reach significance. CONCLUSION: The results of the current study suggest that delay escape is a potent reinforcer at both behavioural and neural levels. Future research should extend this analysis to clinical samples using a broader range of delays and across imaging modalities.

Identifying a distinctive familial frequency band in reaction time fluctuations in ADHD.

OBJECTIVE: Patients with ADHD are typically more variable in their reaction times (RT) than control children. Signal processing analyses have shown that time series RT data of children with ADHD have a distinctive low frequency periodic structure suggestive of a pattern of occasional spontaneous performance lapses. Here we use a fine-grained analysis of spectral power across a broader frequency range to differentiate the periodic qualities of ADHD time series RT data from (a) 1/frequency noise, and (b) control performance. We also assess the familiality of these frequencies by using a proband-sibling design. METHOD: Seventy-one children with ADHD, one of their siblings, and 50 control participants completed a simple RT task. Power across the RT frequency spectrum was calculated. The frequencies significantly differentiating the two groups were identified. Familiality was assessed in two ways: first, by comparing probands with their unaffected siblings and controls, and, second, by investigating the siblings of neuropsychologically impaired and unimpaired children with ADHD. RESULTS: Analyses converged to highlight the potential importance of the .20-.26 Hz band in differentiating the periodic structure of ADHD RT time series data from both 1/frequency noise and control performance. This frequency band also showed the strongest evidence of familiality. CONCLUSIONS: RT performance of children with ADHD had a distinctive periodic structure. The band identified as most differentiating and familial was at a higher frequency than in most previous reports. This highlights the importance of employing tasks with faster interstimulus intervals that will allow a larger portion of the frequency spectrum to be examined.

Attention-induced deactivations in very low frequency EEG oscillations: differential localisation according to ADHD symptom status.

BACKGROUND: The default-mode network (DMN) is characterised by coherent very low frequency (VLF) brain oscillations. The cognitive significance of this VLF profile remains unclear, partly because of the temporally constrained nature of the blood oxygen-level dependent (BOLD) signal. Previously we have identified a VLF EEG network of scalp locations that shares many features of the DMN. Here we explore the intracranial sources of VLF EEG and examine their overlap with the DMN in adults with high and low ADHD ratings. METHODOLOGY/PRINCIPAL FINDINGS: DC-EEG was recorded using an equidistant 66 channel electrode montage in 25 adult participants with high- and 25 participants with low-ratings of ADHD symptoms during a rest condition and an attention demanding Eriksen task. VLF EEG power was calculated in the VLF band (0.02 to 0.2 Hz) for the rest and task condition and compared for high and low ADHD participants. sLORETA was used to identify brain sources associated with the attention-induced deactivation of VLF EEG power, and to examine these sources in relation to ADHD symptoms. There was significant deactivation of VLF EEG power between the rest and task condition for the whole sample. Using s-LORETA the sources of this deactivation were localised to medial prefrontal regions, posterior cingulate cortex/precuneus and temporal regions. However, deactivation sources were different for high and low ADHD groups: In the low ADHD group attention-induced VLF EEG deactivation was most significant in medial prefrontal regions while for the high ADHD group this deactivation was predominantly localised to the temporal lobes. CONCLUSIONS/SIGNIFICANCE: Attention-induced VLF EEG deactivations have intracranial sources that appear to overlap with those of the DMN. Furthermore, these seem to be related to ADHD symptom status, with high ADHD adults failing to significantly deactivate medial prefrontal regions while at the same time showing significant attenuation of VLF EEG power in temporal lobes.

The quick delay questionnaire: a measure of delay aversion and discounting in adults.

Individuals with ADHD often display an altered response to delay. To date, assessment of this has typically involved neuropsychological testing-however, such tests are designed specifically for children and may not be suitable for adults. They are also relatively time-consuming and expensive. In the current paper, we describe the initial validation of a short questionnaire to assess delay-related behaviour in adults. The Quick Delay Questionnaire (QDQ) is a 10-item scale. The questionnaire was administered to 575 participants from the normal population (ranging in age from 18 to 77 years). Forty of the original sample were selected at random and tested 1 week later. Data on ADHD, anxiety and depression were also collected. There were two five-item scales-(1) delay aversion; and (2) delay discounting. These had internal consistency and had good reliability. Subscales were differentially associated with ADHD, anxiety and depression. The QDQ is a potentially valuable way of assessing response to delay in adults. Further work is required to validate the scale against direct observation and neuropsychological assessment in clinically ascertained samples.

Altered spontaneous low frequency brain activity in attention deficit/hyperactivity disorder.

BACKGROUND: Resting brain activity appears altered in Attention Deficit/Hyperactivity Disorder (ADHD). The default mode interference hypothesis (Sonuga-Barke and Castellanos, 2007) postulates that patterns of spontaneous very low frequency brain activity, typical of the resting brain, cause attention lapses in ADHD when they remain unattenuated following the transition from rest to active task performance. Here we test this hypothesis using DC-EEG. METHODS: DC-EEG recordings of very low frequency brain activity (<1.5Hz) were compared for 16 male children with ADHD and 16 healthy controls during both rest and active task performance (two choice reaction time task). RESULTS: A previously identified very low frequency resting network of electrodes was replicated. At rest ADHD children showed less EEG power in very low frequency bands (i.e., .02-.2Hz). They also showed less attenuation of power at these frequency bands during rest-to-task transition. Reduced attenuation was associated with a number of measures of performance. DISCUSSION: We confirmed the existence of altered very low frequency brain activity in ADHD. ADHD children may have deficits both in maintaining a resting brain when needed and 'protecting' an active brain from the intrusion of resting state brain activity.