Search results
Found 778 matches for
A new wearable ‘bike helmet’ style brain scanner, that allows natural movement during scanning, has been used in a study with young children for the first time. This marks an important step towards improving our understanding of brain development in childhood.
Immune response to vaccination in people with psychotic disorders relative to healthy controls: prospective study of SARS-CoV-2 vaccination
This prospective study examines the immune response to SARS-CoV-2 vaccination in patients with psychotic disorders compared with healthy volunteers. Participants were recruited naturalistically as part of the UK's COVID-19 vaccination programme. Prior to receiving their first COVID-19 vaccine, blood samples were provided by participants to examine anti-SARS-CoV-2 immunoglobulins (IgG) at baseline, followed by a repeat assay 1 month after receiving their first vaccine to assess vaccine response. The increase of IgG levels from baseline to 1 month post-vaccination was significantly lower in patients compared with controls, supporting evidence of impaired vaccine response in people with psychotic disorders. When excluding patients treated with clozapine from the analysis, this difference was no longer significant, suggesting that effects may be particularly marked in people taking clozapine.
Reframing pain: the power of individual and societal factors to enhance pain treatment.
The effectiveness of analgesics can be increased if synergistic behavioural, psychological, and pharmacological interventions are provided within a supportive environment.
Identifying factors that can be used to assess a country’s readiness to deploy a new vaccine or improve uptake of an underutilised vaccine: a scoping review
ObjectivesIdentifying whether a country is ready to deploy a new vaccine or improve uptake of an existing vaccine requires knowledge of a diverse range of interdependent, context-specific factors. This scoping review aims to identify common themes that emerge across articles, which include tools or guidance that can be used to establish whether a country is ready to deploy a new vaccine or increase uptake of an underutilised vaccine.DesignScoping review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews guidelines.Data sourcesEmbase, CINAHL, Cochrane Library, Google Scholar, MEDLINE, PsycINFO and Web of Science were searched for articles published until 9 September 2023. Relevant articles were also identified through expert opinion.Eligibility criteriaArticles published in any year or language that included tools or guidance to identify factors that influence a country’s readiness to deploy a new or underutilised vaccine.Data extraction and synthesisTwo independent reviewers screened records and performed data extraction. Findings were synthesised by conducting a thematic analysis.Results38 articles met our inclusion criteria; these documents were created using methodologies including expert review panels and Delphi surveys and varied in terms of content and context-of-use. 12 common themes were identified relevant to a country’s readiness to deploy a new or underutilised vaccine. These themes were as follows: (1) legal, political and professional consensus; (2) sociocultural factors and communication; (3) policy, guidelines and regulations; (4) financing; (5) vaccine characteristics and supply logistics; (6) programme planning; (7) programme monitoring and evaluation; (8) sustainable and integrated healthcare provision; (9) safety surveillance and reporting; (10) disease burden and characteristics; (11) vaccination equity and (12) human resources and training of professionals.ConclusionsThis information has the potential to form the basis of a globally applicable evidence-based vaccine readiness assessment tool that can inform policy and immunisation programme decision-makers.
Sedation Research in Critically Ill Pediatric Patients: Proposals for Future Study Design From the Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research IV Workshop.
OBJECTIVES: Sedation and analgesia for infants and children requiring mechanical ventilation in the PICU is uniquely challenging due to the wide spectrum of ages, developmental stages, and pathophysiological processes encountered. Studies evaluating the safety and efficacy of sedative and analgesic management in pediatric patients have used heterogeneous methodologies. The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research (SCEPTER) IV hosted a series of multidisciplinary meetings to establish consensus statements for future clinical study design and implementation as a guide for investigators studying PICU sedation and analgesia. DESIGN: Twenty-five key elements framed as consensus statements were developed in five domains: study design, enrollment, protocol, outcomes and measurement instruments, and future directions. SETTING: A virtual meeting was held on March 2-3, 2022, followed by an in-person meeting in Washington, DC, on June 15-16, 2022. Subsequent iterative online meetings were held to achieve consensus. SUBJECTS: Fifty-one multidisciplinary, international participants from academia, industry, the U.S. Food and Drug Administration, and family members of PICU patients attended the virtual and in-person meetings. Participants were invited based on their background and experience. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Common themes throughout the SCEPTER IV consensus statements included using coordinated multidisciplinary and interprofessional teams to ensure culturally appropriate study design and diverse patient enrollment, obtaining input from PICU survivors and their families, engaging community members, and using developmentally appropriate and validated instruments for assessments of sedation, pain, iatrogenic withdrawal, and ICU delirium. CONCLUSIONS: These SCEPTER IV consensus statements are comprehensive and may assist investigators in the design, enrollment, implementation, and dissemination of studies involving sedation and analgesia of PICU patients requiring mechanical ventilation. Implementation may strengthen the rigor and reproducibility of research studies on PICU sedation and analgesia and facilitate the synthesis of evidence across studies to improve the safety and quality of care for PICU patients.
Emergency preparedness, resilience and response guidance for UK hospital transfusion teams.
OBJECTIVES: To present Emergency Preparedness, Resilience and Response (EPRR) guidance for Hospital Transfusion Teams on behalf of the National Blood Transfusion Committee emergency planning working group. BACKGROUND: The Civil Contingencies Act 2004 requires healthcare organisations to demonstrate that they can deal with major incidents while maintaining critical services. Recent mass casualty events and the use of transfusion-based resuscitation have highlighted the evolving role of the Hospital Transfusion Team. METHODS: This multi-disciplinary advice is informed by recent global and national experience, the 2018 NHS England clinical guidelines for Major Incidents, and stakeholder workshops. GUIDANCE: Transfusion staff should be familiar with local EPRR plans including casualty type and numbers. Staff should be exercised as part of wider Trust preparation, with documented roles and responsibilities. Transfusion support should be proactive and include blood issue, regulatory compliance and sample handling. Robust LIMS-compatible emergency identification systems are essential to minimise errors. Emergency stock management requires rapid assessment of existing stock and estimated demand before re-ordering. Initial demand should be based on 2 to 4 red blood cells (RBC) per patient admitted. Patients with significant haemorrhage may require further red cells and early haemostatic support. Where "universal" components are demanded, they should be gender appropriate. Senior staff should lead the response, log and communicate key decisions, and prepare for post-incident recovery. CONCLUSIONS: Transfusion teams have an important role in ensuring continuity of transfusion support. Teams should develop their EPRR plans based on local plans and national guidance. Emergency preparedness should include post-incident debriefing for ongoing staff support and future service improvement.
Effect of parental touch on relieving acute procedural pain in neonates and parental anxiety (Petal): a multicentre, randomised controlled trial in the UK.
BACKGROUND: Touch interventions such as massage and skin-to-skin contact relieve neonatal pain. The Parental touch trial (Petal) aimed to assess whether parental stroking of their baby before a clinically required heel lance, at a speed of approximately 3 cm/s to optimally activate C-tactile nerve fibres, provides effective pain relief. METHODS: Petal is a multicentre, randomised, parallel-group interventional superiority trial conducted in the John Radcliffe Hospital (Oxford University Hospitals NHS Foundation Trust, Oxford, UK) and the Royal Devon and Exeter Hospital (Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK). Neonates without neurological abnormalities who were born at 35 weeks gestational age or more and required a blood test via a heel lance in the first week of life were randomly assigned (1:1) to receive parental touch for 10 s either before (intervention group) or after (control group) the clinically required heel lance. Randomisation was managed at the Oxford site using a web-based minimisation algorithm with allocation concealment. The primary outcome measure was the magnitude of noxious-evoked brain activity in response to the heel lance measured with electroencephalography (EEG). Secondary outcome measures were Premature Infant Pain Profile-Revised (PIPP-R) score, development of tachycardia, and parental anxiety score. For all outcomes, the per-protocol effect was estimated via complier average causal effect analysis on the full analysis set. The trial is registered on ISRCTN (ISRCTN14135962) and ClinicalTrials.gov (NCT04901611). FINDINGS: Between Sept 1, 2021, and Feb 7, 2023, 159 parents were approached to participate in the study, and 112 neonates were included. 56 neonates were randomly assigned to the intervention group of parental stroking before the heel lance and 56 to the control group of parental stroking after the heel lance. The mean of the magnitude of the heel lance-evoked brain activity was 0·85 arbitrary units (a.u.; SD 0·70; n=39; a scaled magnitude of 1 a.u. represents the expected mean response to a heel lance in term-aged neonates) in the intervention group and 0·91 a.u. (SD 0·76; n=43) in the control group. Therefore, the primary outcome did not differ significantly between groups, with a mean difference of -0·11 a.u. (lower in intervention group; SD 0·77; 95% CI -0·42 to 0·20; p=0·38; n=82). No significant difference was observed across secondary outcomes. The PIPP-R difference in means was 1·10 (higher in intervention group, 95% CI -0·42 to 2·61; p=0·15; n=100); the odds ratio of becoming tachycardic was 2·08 (95% CI 0·46 to 9·46; p=0·34, n=105) in the intervention group with reference to the control group; and the difference in parental State-Trait Anxiety Inventory-State score was -0·44 (higher in control group; SD 6·85; 95% CI -2·91 to 2·02; p=0·72; n=106). One serious adverse event (desaturation) occurred in a neonate randomly assigned to the control group, which was not considered to be related to the study. INTERPRETATION: Parental stroking delivered at an optimal speed to activate C-tactile fibres for a duration of 10 s before the painful procedure did not significantly change neonates' magnitude of pain-related brain activity, PIPP-R score, or development of tachycardia. The trial highlighted the challenge of translating an experimental researcher-led tactile intervention into a parent-led approach, and the value of involving parents in their baby's pain management. FUNDING: Wellcome Trust and Bliss.
The effect of acute respiratory events and respiratory stimulants on EEG-recorded brain activity in neonates: A systematic review.
OBJECTIVE: We conducted a systematic review to investigate electroencephalography (EEG) changes during periods of acute respiratory events such as apnoea and the effect of respiratory stimulants on EEG features in infants. METHODS: Studies examining respiration and EEG-recorded brain activity in human neonates between 28 and 42 weeks postmenstrual age were included. Two reviewers independently screened all records and included studies were assessed using the Joanna Briggs Institute Critical Appraisal Tool. The protocol was registered in PROSPERO (CRD42022339873). RESULTS: We identified 14 studies with a total of 534 infants. Nine articles assessed EEG changes in relation to apnoea, one assessed hiccups, and four investigated the effect of respiratory stimulants. The relationship between neonatal apnoea and EEG changes was inconsistent; EEG suppression and decreased amplitude and frequency were observed during some, but not all, apnoeas. Respiratory stimulants increased EEG continuity compared with before use. CONCLUSIONS: Current studies in this area are constrained by small sample sizes. Diverse exposure definitions and outcome measures impact inference. SIGNIFICANCE: This review highlights the need for further work; understanding the relationship between respiration and the developing brain is key to mitigating the long-term effects of apnoea.
Statistical analysis plan for the Petal trial: the effects of parental touch on relieving acute procedural pain in neonates
Background: Infants undergo multiple clinically-required painful procedures during their time in hospital, and there is an increasing desire from both parents and clinical staff to have parents directly involved in their newborn’s pain relief. The Petal trial is a multicentre randomised controlled trial to investigate the effect of parental touch prior to a clinically-required heel lance on neonatal pain responses and parental anxiety. To avoid biases due to selective analysis and reporting, a clinical trial’s statistical analysis plan (SAP) should be finalised and registered prior to dataset lock and unblinding. Here, we outline the SAP for the Petal trial, which was registered on the ISRCTN registry prior to dataset lock and unblinding. The SAP is written in line with best practice guidelines to provide sufficient detail for reproducibility. Methods: The primary outcome is the neonate’s brain activity recorded using electroencephalography (EEG) in response to a heel lance blood sampling procedure. In this superiority trial, the primary objective is to investigate the potential efficacy of a parent-led non-pharmacological analgesic intervention on reducing the magnitude of neonates’ noxious stimulus-evoked brain activity. Secondary outcomes include neonatal clinical pain scores and tachycardia, and parental anxiety. Conclusions: Paediatric pain trials have been highlighted by regulatory bodies as an important and challenging topic, with interest increasing in brain imaging outcomes. The Petal trial, to which this SAP relates, is part of a larger effort of establishing a brain-based EEG outcome measure of infant pain for use in clinical trials. This SAP is thus likely to be of interest to those in academia, pharmaceutical companies, and regulatory bodies. We hope this SAP will help establish a foundation for the use of brain imaging outcomes in neonatal pain clinical trials, on which best practices can be built. Trial registration: ClinicalTrials.gov: NCT04901611, 25/05/2021; ISRCTN: ISRCTN14135962, 23/08/2021).
Parental experience of neonatal pain research while participating in the Parental touch trial (Petal)
Abstract Parental involvement in neonatal comfort care is a core component of family-centred care. Yet, parents experience a range of positive and negative feelings when providing pain-relieving interventions for their infants. Parents of infants who participated in the Parental touch trial (Petal), a multicentre randomised controlled trial investigating the impact of gentle parental touch on neonatal pain, were asked to complete an anonymous survey. This survey aimed to (1) explore parent-reported motivations in deciding to participate in the Petal trial; (2) understand parent-reported experiences related to trial participation; (3) understand parents' willingness to participate in future studies; and (4) evaluate parent-reported feelings while they were delivering a gentle touch intervention either before or after a clinically necessary blood test. One hundred six parents (1 parent per infant) took part in the survey. Primary motivators for participation were altruistic. Parents most frequently reported that they wanted their child to take part in the research because it has a potential benefit to babies in the future and because they wanted to improve scientific understanding. Parents reported that providing gentle touch to their children during painful procedures was associated with positive emotions, such as feeling “useful” (64%) and “reassured” (53%). Furthermore, nearly all parents (98%) were pleased to have participated in the Petal trial and would consider, or maybe consider, participating in further research studies. These results underscore the importance of structuring trials around parental involvement and providing opportunities for parents to be involved in providing comfort to their infants during necessary painful clinical procedures.
Inferring the infant pain experience: a translational fMRI-based signature study
AbstractBackgroundIn the absence of verbal communication it is challenging to infer an individual’s sensory and emotional experience. In adults, fMRI has been used to develop multivariate brain activity signatures, which reliably capture elements of human pain experience. We translate whole-brain fMRI signatures that encode pain perception in adults to the newborn infant brain, to advance understanding of functional brain development and pain perception in early life.MethodsA cohort of adults (n=10; mean age=28.3 years) and 2 cohorts of healthy infants (Cohort A: n=15; Cohort B: n=22; mean postnatal age=3 days) were stimulated with low intensity nociceptive stimuli (64-512mN) during acquisition of functional MRI data. fMRI pain signatures were applied directly to the adult data and transformed such that they could be applied to the infant brain. In each cohort, we assessed the concordance of the signatures with the brain responses using cosine-similarity scores, and we assessed stimulus intensity encoding of the signature responses using Spearman rank correlation. Brain activity in ‘pro-pain’ and ‘anti-pain’ brain regions were also examined.FindingsThe Neurologic Pain Signature (NPS), which reflects aspects of nociceptive pain experience, was activated in both the adults and infants, and reliably encoded stimulus intensity. However, the Stimulus Intensity Independent Pain Signature (SIIPS1), which reflects higher-level cognitive modulation of nociceptive input, was only expressed in adults. ‘Pro-pain’ brain regions showed similar activation patterns in adults and infants, whereas, ‘anti-pain’ brain regions exhibited divergent responses.InterpretationBasic intensity encoding of nociceptive information is similar in adults and infants. However, translation of adult brain signatures into infants reveals significant differences in infant cerebral processing of nociceptive information, which may reflect their lack of expectation, motivation and contextualisation. This study expands the use of brain activity pain signatures to non-verbal patients and provides a potential approach to assess analgesic interventions in infancy.FundingThis work was funded by Wellcome (Senior Research Fellowship awarded to Prof. Rebeccah Slater) and SSNAP “Support for Sick and Newborn Infants and their Parents” Medical Research Fund (University of Oxford Excellence Fellowship awarded to Dr Eugene Duff).Research in contextEvidence before this studyWe searched PubMed for research articles published prior to March 2020 using terms including ‘fMRI’, ‘infant or neonate’, and ‘pain or nociception’ in the title or abstract. Due to the relatively new emergence of this field, and the experimental and analytical challenges involved in studying cerebral processing of pain in the MRI environment in healthy newborn infants, only five fMRI studies have examined infant brain responses to nociceptive input.In a foundational pilot study, Williams et al., applied an experimental noxious stimulus to a single infant, evoking widespread brain activity that included several brain regions involved in pain processing in adults. Goksan et al., subsequently performed an observational cohort study and used regional analyses to compare active brain regions in infants (n=10) and adults (n=10), concluding that the evoked patterns of brain activity were broadly similar in infants and adults. Further follow-up analysis in the infant cohort revealed that the functional connectivity of brain regions involved in descending pain modulation influences the magnitude of pain-related brain activity. Two further studies focused on methodological advances, providing evidence-based recommendations for fMRI acquisition parameters and image processing in order to maximise the quality of infant data, and these methods have been implemented in this study.Added value of this studyThis study translates validated adult pain fMRI brain signatures to a nonverbal patient population in which the assessment and management of pain presents a significant clinical challenge. Application of fMRI brain signatures to newborn infants expands on previous fMRI studies that provided only qualitative evidence that noxious stimulation commonly activates brain regions in the adult and infant brain. Here we demonstrate that the basic encoding of the sensory discriminative aspects of pain, as represented by the Neurologic Pain Signature (NPS), occurs in both adults and infants, whereas higher-level cognitive modulation of pain, represented by the Stimulus Intensity Independent Pain Signature (SIIPS1) is only present in adults and not observed in infants. The differences in how the immature infant brain processes pain, relative to the mature adult brain, are likely to reflect differences in their expectation, motivation and contextualisation of external events rather than differences in their core nociceptive cerebral processing of pain. This work allows us to use quantitative fMRI observations to make stronger inferences related to pain experience in nonverbal infants.Implications of all the available evidenceBehavioural pain scores used in neonatal clinical care offer limited sensitivity and specificity to pain. Neonatal clinical trials that use these scores as outcome measures frequently report a lack of efficacy of common analgesic interventions, resulting in few evidence-based drugs for treating pain. The value of using brain-based neuroimaging markers of pain as a means of providing objective evidence of analgesic efficacy in early proof of concept studies is well recognised in adults, even in the absence of behavioural pain modulation. Similarly, in infants EEG-based measures of noxious-evoked brain activity have been used as outcome measures in clinical trials of analgesics to overcome some of the inherent limitations of using behavioural observations to quantify analgesic efficacy. Considering the successful translation of the Neurologic Pain Signature (NPS) and its sensitivity to analgesic modulation in adults, this novel methodology represents an objective brain-based fMRI approach that could be used to advance the discovery and assessment of analgesic interventions in infancy.
The PiNe box: Development and validation of an electronic device to time-lock multimodal responses to sensory stimuli in hospitalised infants
Recording multimodal responses to sensory stimuli in infants provides an integrative approach to investigate the developing nervous system. Accurate time-locking across modalities is essential to ensure that responses are interpreted correctly, and could also improve clinical care, for example, by facilitating automatic and objective multimodal pain assessment. Here we develop and assess a system to time-lock stimuli (including clinically-required heel lances and experimental visual, auditory and tactile stimuli) to electrophysiological research recordings and data recorded directly from a hospitalised infant’s vital signs monitor. The electronic device presented here (that we have called ‘the PiNe box’) integrates a previously developed system to time-lock stimuli to electrophysiological recordings and can simultaneously time-lock the stimuli to recordings from hospital vital signs monitors with an average precision of 105 ms (standard deviation: 19 ms), which is sufficient for the analysis of changes in vital signs. Our method permits reliable and precise synchronisation of data recordings from equipment with legacy ports such as TTL (transistor-transistor logic) and RS-232, and patient-connected networkable devices, is easy to implement, flexible and inexpensive. Unlike current all-in-one systems, it enables existing hospital equipment to be easily used and could be used for patients of any age. We demonstrate the utility of the system in infants using visual and noxious (clinically-required heel lance) stimuli as representative examples.