Anesthetic neurotoxicity in the developing brain: an update on theinsights and implications for fetal surgery.

This review describes an in-depth analysis of the neurotoxicity associated with the anesthetic agents used during fetal surgery, intending to highlight the importance of understanding the effects of general anesthetics on the developing brain, particularly in the context of open fetal surgery, where high doses are applied to facilitate surgical access and augment uterine relaxation. We examined evidence from preclinical studies in rodents and primates, along with studies in human subjects, with the results collectively suggesting that general anesthetics can disrupt brain development and lead to long-lasting neurological deficits. Our review underscores the clinical implications of these findings, indicating an association between extensive anesthetic exposure in early life and subsequent cognitive deficits. The current standard of anesthetic care for fetal surgical procedures was scrutinized, and recommendations have been proposed to mitigate the risk of anesthetic neurotoxicity. These recommendations emphasize the need for careful selection of anesthetic techniques to minimize fetal exposure to potentially harmful agents. In conclusion, while the benefits of fetal surgery in addressing immediate risks often outweigh the potential neurotoxic effects of anesthesia, the long-term developmental impacts nevertheless warrant consideration. Our analysis suggests that the use of general anesthetics in fetal surgery, especially at high doses, poses a significant risk of developmental neurotoxicity. As such, it is imperative to explore safer alternatives, such as employing different methods of uterine relaxation and minimizing the use of general anesthetics, to achieve the necessary surgical conditions. Further research, particularly in clinical settings, is essential to fully understand the risks and benefits of anesthetic techniques in fetal surgery.

Prevalence and risk factors of parental mental health problems: A cross-sectional study.

An understanding of the prevalence and risk factors of parental mental health problems is important for early intervention and prevention measures and shaping services for parents and their children. However, large representative surveys of parental mental health problems and associated risk factors are lacking. The aim of this study was to estimate prevalence rates of parental mental health problems using a standardised measure of psychiatric morbidity (General Health Questionnaire; GHQ-12), in a representative sample of parents and caregivers of children and young people (2-19 years) in Northern Ireland. Further, this study explored associated risk factors of parental mental health problems. A random household survey of parents and children was conducted between June 2019 and March 2020. Parental responses on demographic, economic, familial and psychological measures were collected (N = 2815) and 22% of parents and caregivers screened positive for mental health problems. The STROBE checklist for observational research was adhered to. Multivariate logistic regression indicated that being in receipt of benefits, having poor family support, a history of adverse childhood experiences, a history of exposure to politically motivated violence (the Troubles), and a child with conduct problems and poor health were all independent risk factors of increased parental mental health problems. Findings will help to inform future commissioning and development of services and broaden understanding of the correlates of parental mental health problems.

Psychological distress, wellbeing and resilience: modelling adolescent mental health profiles during the COVID-19 pandemic.

There has been concern about adolescent mental health during the pandemic. The current study examined adolescent mental health during the initial phase of the COVID-19 pandemic in the UK. Using indicator of psychological distress, wellbeing and resilience, latent profile analysis was used to identify homogeneous mental health groups among young people aged 13-24 (N = 1971). Multinomial logistic regression was then used to examine which sociodemographic and psychosocial variables predicted latent class membership. Four classes were found. The largest class (Class 1, 37.2%) was characterised by moderate symptomology and moderate wellbeing. Class 2 (34.2%) was characterised by low symptomology and high wellbeing, while Class 3 (25.4%) was characterised by moderate symptomology and high wellbeing. Finally, Class 4 was the smallest (3.2%) and was characterised by high symptomology and low wellbeing. Compared to the low symptomology, high wellbeing class, all other classes were associated with less social engagement with friends, poorer family functioning, greater somatic symptoms, and a less positive model of self. A number of unique associations between the classes and predictor variables were identified. Although around two-thirds of adolescents reported moderate-to-high symptomology, most of these individuals also reported concurrent moderate-to-high levels of wellbeing, reflecting resilience. Furthermore, these findings demonstrate how a more comprehensive picture of mental health can be gained through adopting a dual-continua conceptualisation of mental health that incorporates both pathology and well-being. In this way, at-risk youth can be identified and interventions and resources targeted appropriately.

Real-time classification of tumour and non-tumour tissue in colorectal cancer using diffuse reflectance spectroscopy and neural networks to aid margin assessment.

BACKGROUND: Colorectal cancer is the third most commonly diagnosed malignancy and the second leading cause of mortality worldwide. A positive resection margin following surgery for colorectal cancer is linked with higher rates of local recurrence and poorer survival. The authors investigated diffuse reflectance spectroscopy (DRS) to distinguish tumour and non-tumour tissue in ex-vivo colorectal specimens, to aid margin assessment and provide augmented visual maps to the surgeon in real-time. METHODS: Patients undergoing elective colorectal cancer resection surgery at a London-based hospital were prospectively recruited. A hand-held DRS probe was used on the surface of freshly resected ex-vivo colorectal tissue. Spectral data were acquired for tumour and non-tumour tissue. Binary classification was achieved using conventional machine learning classifiers and a convolutional neural network (CNN), which were evaluated in terms of sensitivity, specificity, accuracy and the area under the curve. RESULTS: A total of 7692 mean spectra were obtained for tumour and non-tumour colorectal tissue. The CNN-based classifier was the best performing machine learning algorithm, when compared to contrastive approaches, for differentiating tumour and non-tumour colorectal tissue, with an overall diagnostic accuracy of 90.8% and area under the curve of 96.8%. Live on-screen classification of tissue type was achieved using a graduated colourmap. CONCLUSION: A high diagnostic accuracy for a DRS probe and tracking system to differentiate ex-vivo tumour and non-tumour colorectal tissue in real-time with on-screen visual feedback was highlighted by this study. Further in-vivo studies are needed to ensure integration into a surgical workflow.

The network structure of psychopathological and resilient responses to the pandemic: A multicountry general population study of depression and anxiety.

Commonly identified patterns of psychological distress in response to adverse events are characterized by resilience (i.e., little to no distress), delayed (i.e., distress that increases over time), recovery (i.e., distress followed by a gradual decrease over time), and sustained (i.e., distress remaining stable over time). This study aimed to examine these response patterns during the COVID-19 pandemic. Anxiety and depressive symptom data collected across four European countries over the first year of the pandemic were analyzed (N = 3,594). Participants were first categorized into groups based on the four described patterns. Network connectivity and symptom clustering were then estimated for each group and compared. Two thirds (63.6%) of the sample displayed a resilience pattern. The sustained distress network (16.3%) showed higher connectivity than the recovery network (10.0%) group, p = .031; however, the resilient network showed higher connectivity than the delayed network (10.1%) group, p = .016. Regarding symptom clustering, more clusters emerged in the recovery network (i.e., three) than the sustained network (i.e., two). These results replicate findings that resilience was the most common mental health pattern over the first pandemic year. Moreover, they suggest that high network connectivity may be indicative of a stable mental health response over time, whereas fewer clusters may be indicative of a sustained distress pattern. Although exploratory, the network perspective provides a useful tool for examining the complexity of psychological responses to adverse events and, if replicated, could be useful in identifying indicators of protection against or vulnerability to future psychological distress.

Genetic and immune landscape evolution in MMR-deficient colorectal cancer.

Mismatch repair-deficient (MMRd) colorectal cancers (CRCs) have high mutation burdens, which make these tumours immunogenic and many respond to immune checkpoint inhibitors. The MMRd hypermutator phenotype may also promote intratumour heterogeneity (ITH) and cancer evolution. We applied multiregion sequencing and CD8 and programmed death ligand 1 (PD-L1) immunostaining to systematically investigate ITH and how genetic and immune landscapes coevolve. All cases had high truncal mutation burdens. Despite pervasive ITH, driver aberrations showed a clear hierarchy. Those in WNT/ß-catenin, mitogen-activated protein kinase, and TGF-ß receptor family genes were almost always truncal. Immune evasion (IE) drivers, such as inactivation of genes involved in antigen presentation or IFN-γ signalling, were predominantly subclonal and showed parallel evolution. These IE drivers have been implicated in immune checkpoint inhibitor resistance or sensitivity. Clonality assessments are therefore important for the development of predictive immunotherapy biomarkers in MMRd CRCs. Phylogenetic analysis identified three distinct patterns of IE driver evolution: pan-tumour evolution, subclonal evolution, and evolutionary stasis. These, but neither mutation burdens nor heterogeneity metrics, significantly correlated with T-cell densities, which were used as a surrogate marker of tumour immunogenicity. Furthermore, this revealed that genetic and T-cell infiltrates coevolve in MMRd CRCs. Low T-cell densities in the subgroup without any known IE drivers may indicate an, as yet unknown, IE mechanism. PD-L1 was expressed in the tumour microenvironment in most samples and correlated with T-cell densities. However, PD-L1 expression in cancer cells was independent of T-cell densities but strongly associated with loss of the intestinal homeobox transcription factor CDX2. This explains infrequent PD-L1 expression by cancer cells and may contribute to a higher recurrence risk of MMRd CRCs with impaired CDX2 expression. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

ICD-11 prolonged grief disorder: Prevalence, predictors, and co-occurrence in a large representative sample.

The International Classification of Diseases has recently defined Prolonged Grief Disorder (PGD) with symptoms such as longing, worry, and intense emotional pain that exceed sociocultural norms more than 6 months after the loss. This study aims to (a) estimate the prevalence of this new diagnostic category, (b) identify its sociodemographic and loss-related predictors, and (c) assess the co-occurrence of PGD with other psychological disorders and substance abuse. A large representative sample of Spanish adults (N = 1498) participated. Several multivariate binary logistic regression and multivariate logistic regression models were used. Results showed a 9.95% prevalence in the total sample. Catholic beliefs were a positive predictor, while higher income and more time since loss significantly decreased the odds of PGD. PGD significantly increased the likelihood of anxiety, depression, somatisation, post-traumatic stress disorder, loneliness and substance use. Our study contributes to assessing the multicultural PGD validity, as our results from a large representative sample are comparable to those in other countries with the PGDS. Our findings have direct implications for the assessment and treatment of bereavement, identifying for practitioners variables that make individuals more vulnerable to PGD. Results highlighted the high co-occurrence of PGD with other psychological illnesses and increased drug use.

A systematic review and a meta-analysis on the incidence of obstetric anal sphincter injuries during vaginal delivery.

AIM: The incidence of obstetric anal sphincter injuries (OASIS) has increased in the past two decades despite improved awareness of the risk factors. This study aimed to define the incidence of OASIS in women with different features (instrumental delivery or other variables). METHODS: A systematic review was conducted on articles reporting the incidence of OASIS. This review aims to examine the association of instrumentation and OASIS by performing a formal systematic review of the published literature. Databases used for the research were MEDLINE, Embase, CINAHL and 'Maternity and infant care' databases. RESULTS: Two independent reviewers screened the selected articles. 2326 duplicates were removed from the total of 4907 articles. The remaining 2581 articles were screened for title and abstract. 1913 articles were excluded due to irrelevance. The remaining 300 were screened as full text. Primiparity associated with the use of forceps were the features associated with the highest incidence of OASIS in the selected articles (19.4%). OASIS in all women had an overall incidence of 3.8%. The incidence of OASIS in all women by geographical region was the highest (6.5%) in North America. CONCLUSIONS: There are various factors that impact on the incidence of OASIS and the combination of some of these, such as the use of forceps in primiparas, resulted in the highest incidence of OASIS. The lack of international consensus is limiting the improvements that can be done to reduce OASIS rates and improve best clinical practice.

UK trial of pressurised intraperitoneal aerosolised chemotherapy (PIPAC) with oxaliplatin for colorectal cancer peritoneal metastases (NCT03868228).

Objectives: This is the first UK trial of pressurised intraperitoneal aerosolised chemotherapy (PIPAC) for colorectal cancer peritoneal metastases. This trial aimed to assess the impact of PIPAC in combination with standard of care systemic treatment on: progression free survival (PFS); quality of life (QoL); and short-term complications. In addition, this trial set out to demonstrate that PIPAC can be performed safely in operating theatres within a National Health Service (NHS) setting. Methods: Single-centre clinical trial with prospective data collection for patients undergoing 8-weekly PIPAC with oxaliplatin at 92 mg/m2 from January 2019 till January 2022. Progression free survival was assessed using peritoneal carcinomatosis index (PCI) by CT scans and laparoscopy. Quality of life was assessed by EORTC QLQ-C30 questionnaire. Adverse events were recorded using CTCAE. Results: Five patients underwent a total of ten PIPAC administrations (median 2, range 1-4). Median PFS was 6.0 months. QoL was maintained across repeat PIPAC procedures but a decrease in social functioning and increased fatigue were evident. Three incidences of grade 3 adverse events occurred but PIPAC was well tolerated. Conclusions: The presented data demonstrates that PIPAC is feasible and can be safely delivered within the NHS for patients with colorectal cancer peritoneal metastases, but caution must also be exercised given a risk of adverse events. Systemic chemotherapy can be safely administered at a different unit to the PIPAC procedure if both groups have clear lines of communication and timely data sharing.

Primary Care Antibiotic Prescribing and Infection-Related Hospitalisation.

Inappropriate prescribing of antibiotics has been widely recognised as a leading cause of antimicrobial resistance, which in turn has become one of the most significant threats to global health. Given that most antibiotic prescriptions are issued in primary care settings, investigating the associations between primary care prescribing of antibiotics and subsequent infection-related hospitalisations affords a valuable opportunity to understand the long-term health implications of primary care antibiotic intervention. A narrative review of the scientific literature studying associations between primary care antibiotic prescribing and subsequent infection-related hospitalisation was conducted. The Web of Science database was used to retrieve 252 potentially relevant studies, with 23 of these studies included in this review (stratified by patient age and infection type). The majority of studies (n = 18) were published in the United Kingdom, while the remainder were conducted in Germany, Spain, Denmark, New Zealand, and the United States. While some of the reviewed studies demonstrated that appropriate and timely antibiotic prescribing in primary care could help reduce the need for hospitalisation, excessive antibiotic prescribing can lead to antimicrobial resistance, subsequently increasing the risk of infection-related hospitalisation. Few studies reported no association between primary care antibiotic prescriptions and subsequent infection-related hospitalisation. Overall, the disparate results in the extant literature attest to the conflicting factors influencing the decision-making regarding antibiotic prescribing and highlight the necessity of adopting a more patient-focussed perspective in stewardship programmes and the need for increased use of rapid diagnostic testing in primary care.

The structure of the Prodromal Questionnaire-16 (PQ-16) in a non-help-seeking youth population: Exploratory and confirmatory factor analyses study.

AIMS: The present study aimed to examine the structure of the Prodromal Questionnaire-16 (PQ-16) in a non-help-seeking youth population through exploratory and confirmatory factor analysis. Previous studies have not examined the structure of this self-report measure in this age group outside a clinical setting. METHODS: Participants (n = 1165) aged 11-19 years were recruited to an epidemiological study of young people in Northern Ireland, and completed the PQ-16 alongside other measures. The dataset was split randomly in two for separate factor analyses. A polychoric correlation matrix was created and exploratory factor analysis was used to identify the optimal number of factors. In addition, based on previous studies, six models were tested through confirmatory factor analysis to determine best fit. A one-factor, 3 two-factor, a three-factor and a four-factor model were all tested. RESULTS: The exploratory factor analysis indicated a two-factor structure of the PQ-16 in this population, which we have labelled 'general unusual experiences' and 'hallucinations'. Confirmatory analysis indicated that the two-factor model identified through the exploratory analysis was the best fit for the data. DISCUSSION: The present study suggests that the structure of the PQ-16 may vary across age groups in non-clinical settings, and adds further support to the validity of the PQ-16 is a cost-effective, easy to administer self-report measure that is suitable for use in non-help-seeking populations as a screening tool for prodromal symptoms.

Testing the latent structure of ICD-11 prolonged grief disorder symptoms in the U.K. adult population: An exploratory structural equation modeling approach.

The latent structure of ICD-11 prolonged grief disorder (PGD), as measured using the International Prolonged Grief Disorder Scale (IPGDS), was assessed in a large general population sample of bereaved adults from the United Kingdom. Data were derived from Wave 5 of the COVID-19 Psychological Research Consortium Study (C19PRC-UK). Exploratory structural equation modeling (ESEM) was used to assess the latent structure of the IPGDS. Identified factors were explored in relation to known correlates (i.e., gender, age of the bereaved, income, bereavement timeframe, age of the deceased) and functional impairment. Three factors-Loss, Emotional Numbing, and Emotional Reactivity-emerged in the best-fitting ESEM model, χ2 (92, N = 1,763) = 273.70, p < .001, CFI = .97, TLI = .96, RMSEA = .048, SRMR = .020. All factors were significantly associated with bereavement timeframe, ßs = -.15--.20, and age of the deceased, ßs = -.22--.31. Lower income predicted both Loss and Emotional Numbing; younger age of the bereaved predicted both Loss and Emotional Reactivity; and female gender was a unique predictor of Loss. Functional impairment was associated only with Emotional Numbing, ß = .89. The findings highlight the multidimensional structure of PGD. However, the patterns of factor/cross-factor loadings observed in the present study indicate that a "simple" structure was not attainable. Associations between factors and covariates attest to the discriminant validity of the factors, and the association between Emotional Numbing and functional impairment may afford clinicians an opportunity to better understand and target the most disruptive features of grief.

A prospective case series assessing the Imperial College London intraoperative radiotherapy protocol for advanced rectal cancer: an IDEAL phase 2a study.

AIM: Intraoperative radiotherapy (IORT) decreases local recurrence rates for advanced rectal cancer. Nevertheless, utilization of IORT is limited due to the associated logistical and financial challenges. The aim of this study is to describe the development and delivery of a novel IORT protocol for advanced rectal cancer that overcomes these difficulties in the context of the early phase of an IDEAL 2a study. The primary outcome measure was the ability to deliver IORT using this novel protocol with IORT-related toxicity as the secondary outcome measure. METHOD: Consecutive patients with advanced rectal cancer expected to have involved (R1) resection margins were enrolled. After resection, 12 Gy low-energy photon IORT was delivered using the Axxent device with a custom-designed elliptical spherical balloon applicator. RESULTS: Six patients with a median age of 47 years (range 33-88 years; five women) were enrolled between 2018 and 2019. The indication was advanced cancer in four patients and atypical invasive pelvic side wall lymph nodes in two. IORT was successfully delivered in all cases. No toxicity was encountered. Three advanced cancer patients had R1 resection and one had complete resection (R0); resection margin status could not be established for the two lymph node cases. Five patients were alive at 3.4 (2.9-4.1) year follow-up. None of the R1 cases recurred. CONCLUSION: This is the first study to describe a novel IORT protocol using low-energy photon IORT for advanced rectal cancer. IORT could be delivered in all cases and no IORT-related toxicity was encountered. Available oncological outcome data are encouraging, but further studies will be necessary to determine the oncological effectiveness of this protocol.

A protocol for a pilot study to assess the feasibility of a randomised clinical trial of perioperative intravenous lidocaine on colorectal cancer outcome after surgery (FLICOR trial).

Background: Cancer recurrence after curative cancer surgery significantly impacts patients and healthcare services. Before surgery, a small number of clinically undetectable circulating tumour cells are often present. The surgical stress response promotes the distribution and proliferation of circulating tumour cells leading to cancer recurrence and metastasis. Preclinical evidence suggests that lidocaine may exert 'anti-cancer' effects and alleviate pro-metastatic environments. The Feasibility Study of Lidocaine Infusion During Bowel Cancer Surgery for Cancer Outcome (FLICOR) will assess the feasibility of conducting a clinical trial on perioperative intravenous lidocaine infusion for postoperative colorectal cancer outcomes. Methods: The study is a double-blinded, randomised, controlled pilot study for a full trial comparing intravenous lidocaine administration at 1.5 mg kg-1 bolus followed by 1.5 mg kg-1 h-1 infusion for 24 h with placebo in patients undergoing minimally invasive (laparoscopy or robotic) colorectal cancer surgery. The feasibility of data collection instruments will be measured, including those for future economic evaluation and clinical and patient-reported outcomes. For the exploratory outcomes, blood samples will be collected before and after surgery on days 0, 1, and 3. Recruitment is planned for two NHS Trusts over 6 months with a 12-month follow-up. Patients and clinicians will be asked for their feedback on the study process. Dissemination plan: Study data will be disseminated to trial participants, the public, and academic communities. The work will be presented at national and international conferences to stimulate interest and enthusiasm for centres to participate in the future definitive trial. This research will also be published in peer-reviewed open-access journals. Clinical trial registration: ISRCTN29594895 (ISRCTN), NCT05250791 (ClinicalTrials.gov). Protocol version number and date: 3.0, February 8, 2023.

Predicting resilience during the COVID-19 Pandemic in the United Kingdom: Cross-sectional and longitudinal results.

Although the COVID-19 pandemic has impacted the psychological wellbeing of some people, there is evidence that many have been much less affected. The Ecological Model of Resilience (EMR) may explain why some individuals are not resilient whilst others are. In this study we test the EMR in a comparison of UK survey data collected from the COVID-19 Psychological Research Consortium (C19PRC) longitudinal study of a representative sample of the United Kingdom (UK) adult population and data from an Italian arm of the study. We first compare data from the third wave of the UK arm of the study, collected in July/August 2020, with data from an equivalent sample and stage of the pandemic in Italy in July 2020. Next, using UK longitudinal data collected from C19PRC Waves 1, 3 and 5, collected between March 2020 and April 2021 we identify the proportion of people who were resilient. Finally, we examine which factors, drawn from the EMR, predict resilient and non-resilient outcomes. We find that the 72% of the UK sample was resilient, in line with the Italian study. In the cross-sectional logistic regression model, age and self-esteem were significantly associated with resilience whilst death anxiety thoughts, neuroticism, loneliness, and Post Traumatic Stress Disorder (PTSD) symptoms related to COVID-19 were significantly associated with Non-Resilient outcomes. In the longitudinal UK analysis, at Wave 5, 80% of the sample was Resilient. Service use, belonging to wider neighbourhood, self-rated health, self-esteem, openness, and externally generated death anxiety were associated with Resilient outcomes. In contrast, PTSD symptoms and loneliness were associated with Non-Resilient outcomes. The EMR effectively explained the results. There were some variables which are amenable to intervention which could increase resilience in the face of similar future challenges.

The Development and Feasibility of an Empathy Virtual Reality Scenario in Healthcare Education.

Technology-enhanced simulations such as virtual reality and computer-based experiences allow students to improve their understanding of patient perspectives and increase empathy for patients. These technologies can be daunting to nursing faculty without robust technology and video development resources. The purpose of this project was to share a guide for creating and implementing a patient-centered immersive virtual reality scenario within a nursing program. The research team developed, filmed, and produced a cost-effective virtual reality simulation scenario for use with smartphones and inexpensive virtual reality headsets, which could be widely disseminated for students to watch in class or online. The virtual reality simulation allowed an immersive first-person view and was well received by both faculty and students. The virtual reality scenario was implemented with ease in classroom, virtual, and laboratory settings. These virtual reality simulations work in the live setting or remotely, and synchronously or asynchronously with minimal equipment, which reduces barriers to access.

Functioning, symptom expression and risk along the psychosis continuum.

BACKGROUND: The psychosis continuum implies that subclinical psychotic experiences (PEs) can be differentiated from clinically relevant expressions since they are not accompanied by a 'need for care'. METHODS: Using data from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; N = 34 653), the current study examined variation in functioning, symptomology and aetiological risk across the psychosis phenotype [i.e. variation from (i) no PEs, 'No PEs' to (ii) non-distressing PEs, 'PE-Experienced Only' to (iii) distressing PEs, 'PE-Impaired' to (iv) clinically defined psychotic disorder, 'Diagnosed']. RESULTS: A graded trend was present such that, compared to those with no PEs, the Diagnosed group had the poorest functioning, followed by the PE-Impaired then PE-Experienced Only groups. In relation to symptom expression, the PE-Impaired group were more likely than the PE-Experienced Only and the Diagnosed groups to endorse most PEs. Predictors of group membership tended to vary quantitatively rather than qualitatively. Trauma, current mental health diagnoses (anxiety and depression) and drug use variables differentiated between all levels of the continuum, with the exception of the extreme end (PE-Impaired v. Diagnosed). Only a few variables distinguished groups at the upper end of the continuum: female sex, older age, unemployment, parental mental health hospitalisation and lower likelihood of having experienced physical assault. CONCLUSIONS: The findings highlight the importance of continuum-based interpretations of the psychosis phenotype and afford valuable opportunities to consider if and how impairment, symptom expression and risk change along the continuum.

Symptoms and levels of ICD-11 Prolonged Grief Disorder in a representative community sample of UK adults.

BACKGROUND: Prolonged Grief Disorder (PGD) is a new disorder included in ICD-11 (WHO, 2018). There is a growing body of literature surrounding the prevalence and correlates of ICD-11 PGD symptoms as assessed using various measures. This study was the first to assess levels of ICD-11 PGD symptoms as measured by the International Prolonged Grief Disorder Scale (IPGDS), a self-report scale directly aligned with the ICD-11 definition of PGD, among the United Kingdom adult general population, and identify correlates. METHOD: Participants included 2025 adults who participated in Wave 5 of the COVID-19 Psychological Research Consortium Study (C19PRC-UK). Prevalence rates of PGD were estimated based on two commonly used algorithms defined as 'strict' and 'moderate'. Sociodemographic, loss-related, and mental health correlates (i.e., anxiety, depression, mental health treatment seeking, loneliness) of strict and moderate PGD were then examined using multinomial logistic regressions. RESULTS: It was found that 2.4% (n = 43) of participants met probable caseness for PGD using the strict criteria while 7.9% (n = 140) met probable caseness for PGD using the moderate criteria. Multinomial logistic regression analysis results showed, as predicted, that income, time since bereavement, death of a child, religiosity, and depression were associated with both moderate and strict PGD. Correlates of moderate PGD included country of residence, urbanicity, younger age of bereaved, and loneliness. CONCLUSIONS: This study highlights that some symptoms of PGD are commonly reported in the general population, although relatively few meet the criteria for clinical significance. The routine assessment for PGD following a bereavement is discussed and the development of appropriate interventions are recommended.

The influence of adverse and positive childhood experiences on young people's mental health and experiences of self-harm and suicidal ideation.

BACKGROUND: Few studies have examined the interaction of adverse childhood experiences (ACEs) and positive childhood experiences (PCEs) with mental health outcomes in nationally representative European populations. OBJECTIVE: The primary objective was to test models of resilience through investigating associations between ACEs and PCEs and young people's risk of common mood and anxiety disorders, self-harm and suicidal ideation. PARTICIPANTS AND SETTING: Data were from the Northern Ireland Youth Wellbeing Survey (NIYWS), a stratified random probability household survey conducted between June 2019 and March 2020. Analysis is based on data from adolescents aged 11-19 years (n = 1299). METHOD: Logistic regression was used to test the direct effects of ACEs and PCEs on mental health outcomes and the moderating effect of PCEs at different levels of ACE exposure. RESULTS: Prevalence rates of mental health outcomes were: common mood and anxiety disorders (16 %); self-harm (10 %); suicidal ideation (12 %). ACEs and PCEs both independently predicted common mood and anxiety disorders, self-harm and suicidal ideation. Every additional ACE increased the likelihood of a common mood and anxiety disorder (81 %), self-harm (88 %) and suicidal ideation (88 %). Every additional PCE reduced common mood and anxiety disorders (14 %), self-harm (13 %) and suicidal ideation (7 %). There was no moderating effect of PCEs on ACEs and mental health outcomes. CONCLUSION: The findings suggest that PCEs act largely independently of ACEs and that initiatives to increase PCEs can assist in the prevention of mental health problems.

Liver transplantation for isolated unresectable colorectal liver metastases - Protocol for a service evaluation in the United Kingdom - UKCoMET study.

BACKGROUND: Liver transplantation (LT) for unresectable colorectal liver metastases (CRCLM) demonstrates good overall survival for selected patients in contemporary studies, with 5-year survival of 80%. A Fixed Term Working Group (FTWG), set up by NHS Blood and Transplant (NHSBT) Liver Advisory Group (LAG), advised whether CRCLM should be considered for LT in United Kingdom. Their recommendation was that LT may be undertaken for isolated and unresectable CRCLM using strict selection criteria as a national clinical service evaluation. METHODS: Opinions were sought from colorectal cancer/LT patient representatives, experts in colorectal cancer surgery/oncology, LT surgery, hepatology, hepatobiliary radiology, pathology, and nuclear medicine, and appropriate patient selection criteria, referral and transplant listing pathways were identified. RESULTS: This paper summarises selection criteria for LT in United Kingdom for isolated and unresectable CRCLM patients, and highlights referral framework and pre-transplant assessment criteria. Finally, oncology-specific outcome measures to be utilised for assessing applicability of LT are described. CONCLUSION: This service evaluation represents a significant development for colorectal cancer patients in United Kingdom and a meaningful step forward in the field of transplant oncology. This paper details the protocol for the pilot study, scheduled to begin in the fourth quarter of 2022 in United Kingdom.