Tripping into the unknown: Exploring the experiences of first-time LSD users through global drug survey insights.

BACKGROUND: The recreational use of LSD, a synthetic psychedelic drug, has surged in recent years, coinciding with a renewed research focus on its potential psychotherapeutic properties. AIM: This study aims to describe the experiences and perceptions of individuals engaging in LSD use for the first time, derived from a large international sample. METHODS: This study utilised 2018 Global Drug Survey data collected from 6 November 2017 to 10 January 2018. Participants who initiated LSD use in the preceding 12 months answered questions on their experiences, social settings, harm-reduction behaviours, and demographics. Descriptive statistics were employed, and characteristics of those seeking emergency medical treatment (EMT) and those not planning further LSD use were compared with other respondents. RESULTS: Among 3340 respondents who used LSD in the past year, their first-time experiences generally exceeded expectations, with 97.7% expressing excitement. Adverse and unwanted side effects were rarely reported, and only 17 individuals needed EMT. Feelings of fear were reported by most (64.1%), but only very mildly and not enough to put them off from wanting to use LSD again. DISCUSSION: Although the occurrence of unwanted side effects seems low and the LSD experience is generally pleasurable, vigilance amid the rising illicit use of LSD through harm-reduction education is still important in preventing possible risks.

Identifying characteristics that enable resilient immunisation programmes: a scoping review.

OBJECTIVES: The COVID-19 pandemic highlighted the fragility of immunisation programmes and resulted in a significant reduction in vaccination rates, with increasing vaccine-preventable disease outbreaks consequently reported. These vulnerabilities underscore the importance of resilient immunisation programmes to ensure optimal performance during crises. To date, a framework for assessing immunisation programme resilience does not exist. We conducted a scoping review of immunisation programmes during times of crisis to identify factors that characterise resilient immunisation programmes, which may inform an Immunisation Programme Resilience Tool. DESIGN: Scoping review design followed the Arksey and O'Malley framework, and manuscript reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews guidelines. DATA SOURCES: CINAHL, CENTRAL, Embase, Google Scholar, MEDLINE, PsycINFO and Web of Science and databases were searched between 1 January 2011 and 2 September 2023. Citation searching of identified studies was also performed. ELIGIBILITY CRITERIA: We included primary empirical peer-reviewed studies that discussed the resilience of immunisation programme to crises, shocks or disruptions. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers screened records and performed data extraction. We extracted data on study location and design, crisis description, and resilience characteristics discussed, and identified evidence gaps in the literature. Findings were synthesised using tabulation and an evidence gap map. RESULTS: Thirty-seven studies met the eligibility criteria. These studies captured research conducted across six continents, with most concentrated in Africa, Asia and Europe. One study had a randomised controlled trial design, while 36 studies had observational designs (15 analytical and 21 descriptive). We identified five characteristics of resilient immunisation programmes drawing on the Health System Resilience Index (Integration, Awareness, Resource Availability and Access, Adaptiveness and Self-regulation) and several evidence gaps in the literature. CONCLUSIONS: To our knowledge, no immunisation programme resilience tool exists. We identified factors from the Health System Resilience Index coupled with factors identified through primary empirical evidence, which may inform development of an immunisation programme resilience tool.

Resting state electroencephalographic brain activity in neonates can predict age and is indicative of neurodevelopmental outcome.

OBJECTIVE: Electroencephalography (EEG) can be used to estimate neonates' biological brain age. Discrepancies between postmenstrual age and brain age, termed the brain age gap, can potentially quantify maturational deviation. Existing brain age EEG models are not well suited to clinical cot-side use for estimating neonates' brain age gap due to their dependency on relatively large data and pre-processing requirements. METHODS: We trained a deep learning model on resting state EEG data from preterm neonates with normal neurodevelopmental Bayley Scale of Infant and Toddler Development (BSID) outcomes, using substantially reduced data requirements. We subsequently tested this model in two independent datasets from two clinical sites. RESULTS: In both test datasets, using only 20 min of resting-state EEG activity from a single channel, the model generated accurate age predictions: mean absolute error = 1.03 weeks (p-value = 0.0001) and 0.98 weeks (p-value = 0.0001). In one test dataset, where 9-month follow-up BSID outcomes were available, the average neonatal brain age gap in the severe abnormal outcome group was significantly larger than that of the normal outcome group: difference in mean brain age gap = 0.50 weeks (p-value = 0.04). CONCLUSIONS: These findings demonstrate that the deep learning model generalises to independent datasets from two clinical sites, and that the model's brain age gap magnitudes differ between neonates with normal and severe abnormal follow-up neurodevelopmental outcomes. SIGNIFICANCE: The magnitude of neonates' brain age gap, estimated using only 20 min of resting state EEG data from a single channel, can encode information of clinical neurodevelopmental value.

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.

OBJECTIVES: Identifying 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. DESIGN: Scoping review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews guidelines. DATA SOURCES: Embase, 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 CRITERIA: Articles 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 SYNTHESIS: Two independent reviewers screened records and performed data extraction. Findings were synthesised by conducting a thematic analysis. RESULTS: 38 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. CONCLUSIONS: This 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.

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.

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.

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.

Sensory event-related potential morphology predicts age in premature infants.

OBJECTIVE: We investigated whether sensory-evoked cortical potentials could be used to estimate the age of an infant. Such a model could be used to identify infants who deviate from normal neurodevelopment. METHODS: Infants aged between 28- and 40-weeks post-menstrual age (PMA) (166 recording sessions in 96 infants) received trains of visual and tactile stimuli. Neurodynamic response functions for each stimulus were derived using principal component analysis and a machine learning model trained and validated to predict infant age. RESULTS: PMA could be predicted accurately from the magnitude of the evoked responses (training set mean absolute error and 95% confidence intervals: 1.41 [1.14; 1.74] weeks,p = 0.0001; test set mean absolute error: 1.55 [1.21; 1.95] weeks,p = 0.0002). Moreover, we show that their predicted age (their brain age) is correlated with a measure known to relate to maturity of the nervous system and is linked to long-term neurodevelopment. CONCLUSIONS: Sensory-evoked potentials are predictive of age in premature infants and brain age deviations are related to biologically and clinically meaningful individual differences in nervous system maturation. SIGNIFICANCE: This model could be used to detect abnormal development of infants' response to sensory stimuli in their environment and may be predictive of neurodevelopmental outcome.

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.

Multicentre, randomised controlled trial to investigate the effects of parental touch on relieving acute procedural pain in neonates (Petal).

INTRODUCTION: Newborn infants routinely undergo minor painful procedures as part of postnatal care, with infants born sick or premature requiring a greater number of procedures. As pain in early life can have long-term neurodevelopmental consequences and lead to parental anxiety and future avoidance of interventions, effective pain management is essential. Non-pharmacological comfort measures such as breastfeeding, swaddling and sweet solutions are inconsistently implemented and are not always practical or effective in reducing the transmission of noxious input to the brain. Stroking of the skin can activate C-tactile fibres and reduce pain, and therefore could provide a simple and safe parent-led intervention for the management of pain. The trial aim is to determine whether parental touch prior to a painful clinical procedure provides effective pain relief in neonates. METHODS AND ANALYSIS: This is a multicentre randomised controlled trial. A total of 112 neonates born at 35 weeks' gestation or more requiring a blood test in the first week of life will be recruited and randomised to receive parental stroking either preprocedure or postprocedure. We will record brain activity (EEG), cardiac and respiratory dynamics, oxygen saturation and facial expression to provide proxy pain outcome measures. The primary outcome will be the reduction of noxious-evoked brain activity in response to a heel lance. Secondary outcomes will be a reduction in clinical pain scores (Premature Infant Pain Profile-Revised), postprocedural tachycardia and parental anxiety. ETHICS AND DISSEMINATION: The study has been approved by the London-South East Research Ethics Committee (ref: 21/LO/0523). The results will be widely disseminated through peer-reviewed publications, international conferences and via our partner neonatal charities Bliss and Supporting the Sick Newborn And their Parents (SSNAP). If the parental tactile intervention is effective, recommendations will be submitted via the National Health Service clinical guideline adoption process. STUDY STATUS: Commenced September 2021. TRIAL REGISTRATION NUMBER: NCT04901611; 14 135 962.

Concurrent mapping of brain ontogeny and phylogeny within a common space: Standardized tractography and applications.

Developmental and evolutionary effects on brain organization are complex, yet linked, as evidenced by the correspondence in cortical area expansion across these vastly different time scales. However, it is still not possible to study concurrently the ontogeny and phylogeny of cortical areal connections, which is arguably more relevant to brain function than allometric measurements. Here, we propose a novel framework that allows the integration of structural connectivity maps from humans (adults and neonates) and nonhuman primates (macaques) onto a common space. We use white matter bundles to anchor the common space and use the uniqueness of cortical connection patterns to these bundles to probe area specialization. This enabled us to quantitatively study divergences and similarities in connectivity over evolutionary and developmental scales, to reveal brain maturation trajectories, including the effect of premature birth, and to translate cortical atlases between diverse brains. Our findings open new avenues for an integrative approach to imaging neuroanatomy.

Early life inflammation is associated with spinal cord excitability and nociceptive sensitivity in human infants.

Immune function and sensitivity to pain are closely related, but the association between early life inflammation and sensory nervous system development is poorly understood-especially in humans. Here, in term-born infants, we measure brain activity and reflex withdrawal activity (using EEG and EMG) and behavioural and physiological activity (using the PIPP-R score) to assess the impact of suspected early-onset neonatal infection on tactile- and noxious-evoked responses. We present evidence that neonatal inflammation (assessed by measuring C-reactive protein levels) is associated with increased spinal cord excitability and evoked brain activity following both tactile and noxious stimulation. There are early indications that this hyperalgesia could be maintained post-inflammation, supporting pre-clinical reports of early-life immune dysfunction influencing pain sensitivity in adults.

The Developing Human Connectome Project Neonatal Data Release.

The Developing Human Connectome Project has created a large open science resource which provides researchers with data for investigating typical and atypical brain development across the perinatal period. It has collected 1228 multimodal magnetic resonance imaging (MRI) brain datasets from 1173 fetal and/or neonatal participants, together with collateral demographic, clinical, family, neurocognitive and genomic data from 1173 participants, together with collateral demographic, clinical, family, neurocognitive and genomic data. All subjects were studied in utero and/or soon after birth on a single MRI scanner using specially developed scanning sequences which included novel motion-tolerant imaging methods. Imaging data are complemented by rich demographic, clinical, neurodevelopmental, and genomic information. The project is now releasing a large set of neonatal data; fetal data will be described and released separately. This release includes scans from 783 infants of whom: 583 were healthy infants born at term; as well as preterm infants; and infants at high risk of atypical neurocognitive development. Many infants were imaged more than once to provide longitudinal data, and the total number of datasets being released is 887. We now describe the dHCP image acquisition and processing protocols, summarize the available imaging and collateral data, and provide information on how the data can be accessed.

Premature infants display discriminable behavioral, physiological, and brain responses to noxious and nonnoxious stimuli.

Pain assessment in preterm infants is challenging as behavioral, autonomic, and neurophysiological measures of pain are reported to be less sensitive and specific than in term infants. Understanding the pattern of preterm infants' noxious-evoked responses is vital to improve pain assessment in this group. This study investigated the discriminability and development of multimodal noxious-evoked responses in infants aged 28-40 weeks postmenstrual age. A classifier was trained to discriminate responses to a noxious heel lance from a nonnoxious control in 47 infants, using measures of facial expression, brain activity, heart rate, and limb withdrawal, and tested in two independent cohorts with a total of 97 infants. The model discriminates responses to the noxious from the nonnoxious procedure with an overall accuracy of 0.76-0.84 and an accuracy of 0.78-0.79 in the 28-31-week group. Noxious-evoked responses have distinct developmental patterns. Heart rate responses increase in magnitude with age, while noxious-evoked brain activity undergoes three distinct developmental stages, including a previously unreported transitory stage consisting of a negative event-related potential between 30 and 33 weeks postmenstrual age. These findings demonstrate that while noxious-evoked responses change across early development, infant responses to noxious and nonnoxious stimuli are discriminable in prematurity.

The impact of premature extrauterine exposure on infants' stimulus-evoked brain activity across multiple sensory systems.

Prematurity can result in widespread neurodevelopmental impairment, with the impact of premature extrauterine exposure on brain function detectable in infancy. A range of neurodynamic and haemodynamic functional brain measures have previously been employed to study the neurodevelopmental impact of prematurity, with methodological and analytical heterogeneity across studies obscuring how multiple sensory systems are affected. Here, we outline a standardised template analysis approach to measure evoked response magnitudes for visual, tactile, and noxious stimulation in individual infants (n = 15) using EEG. By applying these templates longitudinally to an independent cohort of very preterm infants (n = 10), we observe that the evoked response template magnitudes are significantly associated with age-related maturation. Finally, in a cross-sectional study we show that the visual and tactile response template magnitudes differ between a cohort of infants who are age-matched at the time of study but who differ according to whether they are born during the very preterm or late preterm period (n = 10 and 8 respectively). These findings demonstrate the significant impact of premature extrauterine exposure on brain function and suggest that prematurity can accelerate maturation of the visual and tactile sensory system in infants born very prematurely. This study highlights the value of using a standardised multi-modal evoked-activity analysis approach to assess premature neurodevelopment, and will likely complement resting-state EEG and behavioural assessments in the study of the functional impact of developmental care interventions.

Longitudinal association between CRP levels and risk of psychosis: a meta-analysis of population-based cohort studies.

Meta-analyses of cross-sectional studies suggest that patients with psychosis have higher circulating levels of C-reactive protein (CRP) compared with healthy controls; however, cause and effect is unclear. We examined the prospective association between CRP levels and subsequent risk of developing a psychotic disorder by conducting a systematic review and meta-analysis of population-based cohort studies. Databases were searched for prospective studies of CRP and psychosis. We obtained unpublished results, including adjustment for age, sex, body mass index, smoking, alcohol use, and socioeconomic status and suspected infection (CRP > 10 mg/L). Based on random effect meta-analysis of 89,792 participants (494 incident cases of psychosis at follow-up), the pooled odds ratio (OR) for psychosis for participants with high (>3 mg/L), as compared to low (≤3 mg/L) CRP levels at baseline was 1.50 (95% confidence interval [CI], 1.09-2.07). Evidence for this association remained after adjusting for potential confounders (adjusted OR [aOR] = 1.31; 95% CI, 1.03-1.66). After excluding participants with suspected infection, the OR for psychosis was 1.36 (95% CI, 1.06-1.74), but the association attenuated after controlling for confounders (aOR = 1.23; 95% CI, 0.95-1.60). Using CRP as a continuous variable, the pooled OR for psychosis per standard deviation increase in log(CRP) was 1.11 (95% CI, 0.93-1.34), and this association further attenuated after controlling for confounders (aOR = 1.07; 95% CI, 0.90-1.27) and excluding participants with suspected infection (aOR = 1.07; 95% CI, 0.92-1.24). There was no association using CRP as a categorical variable (low, medium or high). While we provide some evidence of a longitudinal association between high CRP (>3 mg/L) and psychosis, larger studies are required to enable definitive conclusions.

Functional and diffusion MRI reveal the neurophysiological basis of neonates' noxious-stimulus evoked brain activity.

Understanding the neurophysiology underlying neonatal responses to noxious stimulation is central to improving early life pain management. In this neonatal multimodal MRI study, we use resting-state and diffusion MRI to investigate inter-individual variability in noxious-stimulus evoked brain activity. We observe that cerebral haemodynamic responses to experimental noxious stimulation can be predicted from separately acquired resting-state brain activity (n = 18). Applying this prediction model to independent Developing Human Connectome Project data (n = 215), we identify negative associations between predicted noxious-stimulus evoked responses and white matter mean diffusivity. These associations are subsequently confirmed in the original noxious stimulation paradigm dataset, validating the prediction model. Here, we observe that noxious-stimulus evoked brain activity in healthy neonates is coupled to resting-state activity and white matter microstructure, that neural features can be used to predict responses to noxious stimulation, and that the dHCP dataset could be utilised for future exploratory research of early life pain system neurophysiology.