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.

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.

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.

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.

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.

Refuting the myth of a 'tsunami' of mental ill-health in populations affected by COVID-19: evidence that response to the pandemic is heterogeneous, not homogeneous.

BACKGROUND: The current study argues that population prevalence estimates for mental health disorders, or changes in mean scores over time, may not adequately reflect the heterogeneity in mental health response to the COVID-19 pandemic within the population. METHODS: The COVID-19 Psychological Research Consortium (C19PRC) Study is a longitudinal, nationally representative, online survey of UK adults. The current study analysed data from its first three waves of data collection: Wave 1 (March 2020, N = 2025), Wave 2 (April 2020, N = 1406) and Wave 3 (July 2020, N = 1166). Anxiety-depression was measured using the Patient Health Questionnaire Anxiety and Depression Scale (a composite measure of the PHQ-9 and GAD-7) and COVID-19-related posttraumatic stress disorder (PTSD) with the International Trauma Questionnaire. Changes in mental health outcomes were modelled across the three waves. Latent class growth analysis was used to identify subgroups of individuals with different trajectories of change in anxiety-depression and COVID-19 PTSD. Latent class membership was regressed on baseline characteristics. RESULTS: Overall prevalence of anxiety-depression remained stable, while COVID-19 PTSD reduced between Waves 2 and 3. Heterogeneity in mental health response was found, and hypothesised classes reflecting (i) stability, (ii) improvement and (iii) deterioration in mental health were identified. Psychological factors were most likely to differentiate the improving, deteriorating and high-stable classes from the low-stable mental health trajectories. CONCLUSIONS: A low-stable profile characterised by little-to-no psychological distress ('resilient' class) was the most common trajectory for both anxiety-depression and COVID-19 PTSD. Monitoring these trajectories is necessary moving forward, in particular for the ~30% of individuals with increasing anxiety-depression levels.

United Kingdom criteria for liver transplantation in the setting of isolated unresectable colorectal liver metastases.

AIM: Studies have demonstrated that liver transplantation may be an effective treatment for isolated unresectable colorectal cancer liver metastases (CRCLM). Published data suggest that 5-year survival may be as high as 80%; however, recurrent disease is commonplace. Consequently, the Liver Transplantation for Unresectable Colorectal Liver Metastases Fixed Term Working Unit recommended to the NHS Blood and Transplant Liver Advisory Group that while CRCLM is an appropriate indication for transplantation, selection criteria should be conservative and that it should be undertaken within a clinical service evaluation programme. The aim of this work is to outline the proposed UK selection criteria and follow-up process for CRCLM transplantation. METHOD: Consensus statement by colorectal cancer/liver transplantation patient representatives, experts in colorectal cancer surgery/oncology, liver transplantation surgery, hepatology, hepatobiliary radiology, hepatobiliary pathology and nuclear medicine. RESULTS: This study provides a comprehensive outline of the inclusion/exclusion criteria for referral in the UK. Furthermore, the referral framework is also explained. Pretransplant assessment criteria for listing/delisting are outlined. Finally, the oncology-specific outcome measures posttransplant are described. CONCLUSION: It is anticipated this service will begin in December 2022. A series of educational events for the referrers and transplant units will be arranged throughout 2023 to highlight CRCLM as a newly accepted UK indication for transplantation. A national audit will be undertaken to identify patients currently on treatment who meet the criteria for transplant. Data will be collected in a national registry and reviewed on an ongoing basis to confirm the safety of this treatment and to determine if the inclusion criteria require revision.

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.

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.

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.

Prevalence of probable eating disorders and associated risk factors: An analysis of the Northern Ireland Youth Wellbeing Survey using the SCOFF.

OBJECTIVES: Eating disorders (ED) are associated with significant morbidity and mortality rates and are most common in young people aged between 15 and 19 years. Large representative surveys on disordered eating in youth are lacking. The main aims were to estimate the prevalence of disordered eating in a representative sample of 11-19 year olds in Northern Ireland and investigate the associations between probable eating disorder and a range of risk factors. DESIGNS AND METHODS: A large nationally representative household survey was conducted, and the bivariate and multivariate associations between demographic, familial, economic and psychological risk factors and probable eating disorder were assessed. RESULTS: A total of 16.2% (n = 211) of the sample met the SCOFF screening criteria for disordered eating. Probable eating disorder was associated with being female (OR = 2.44), having a parent with mental health problems (OR = 1.68), suffering from certain psychological problems, such as mood or anxiety disorder (OR = 2.55), social media disorder (OR = 2.95), being the victim of physical bullying (OR = 1.71) and having smoked (OR = 2.46). CONCLUSIONS: This study provides the first prevalence estimates of probable eating disorder among youth in Northern Ireland. Furthermore, the study identifies unique risk factors for probable eating disorder among this representative sample.

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.

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.

Prevalence and predictors of ICD-11 posttraumatic stress disorder and complex PTSD in young people.

OBJECTIVE: The prevalence, construct validity, risk factors and psychopathological correlates associated with ICD-11 posttraumatic stress disorder (PTSD) and complex PTSD (CPTSD) as measured by the International Trauma Questionnaire for Children and Adolescents (ITQ-CA) were assessed in a sample of young people from Northern Ireland. METHOD: Participants were trauma-exposed 11-19-year-olds (N = 507) who participated in the Northern Ireland Youth Wellbeing Prevalence Survey (YWS-NI, 2020). Factor mixture modelling (FMM) was used to test the latent structure of the ITQ-CA. Risk-factors and psychopathological correlates associated with latent class membership, and ICD-11diagnostic status, were also investigated. RESULTS: More participants met the ITQ-CA criteria for CPTSD (3.4%, n = 44) than PTSD (1.5%, n = 19). A second-order FMM comprising a 'partial-PTSD class', a 'CPTSD class', a 'DSO class' and a 'low symptom endorsement class' was the best-fitting model. Younger age and cumulative trauma were risk factors for all trauma classes. Female gender and two or more violent traumas were significant predictors of the 'PTSD' and 'CPTSD' classes, while single sexual trauma was a significant predictor of the 'DSO' and 'CPTSD' classes. Two or more sexual traumas was a unique predictor of 'CPTSD class', while two or more vicarious traumas was a unique predictor of 'DSO class'. The 'CPTSD' class displayed the most notable comorbidity. CONCLUSIONS: Findings indicate that CPTSD may be more prevalent than PTSD in children and young people. Support for the ICD-11 conceptualisation of CPTSD as representing a unique diagnostic construct was supported using FMM, with findings indicating trauma symptom class-specific risk profiles.

Measurement invariance of the Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder scale (GAD-7) across four European countries during the COVID-19 pandemic.

BACKGROUND: The Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder scale (GAD-7) are self-report measures of major depressive disorder and generalised anxiety disorder. The primary aim of this study was to test for differential item functioning (DIF) on the PHQ-9 and GAD-7 items based on age, sex (males and females), and country. METHOD: Data from nationally representative surveys in UK, Ireland, Spain, and Italy (combined N = 6,054) were used to fit confirmatory factor analytic and multiple-indictor multiple-causes models. RESULTS: Spain and Italy had higher latent variable means than the UK and Ireland for both anxiety and depression, but there was no evidence for differential items functioning. CONCLUSIONS: The PHQ-9 and GAD-7 scores were found to be unidimensional, reliable, and largely free of DIF in data from four large nationally representative samples of the general population in the UK, Ireland, Italy and Spain.

Diagnostic accuracy of Abbott Architect Assay as a screening tool for human T-cell leukaemia virus type-1 and type-2 infection in a London teaching hospital with a large solid organ transplant centre.

AIM: In the United Kingdom, organ donors/recipients are screened for evidence of human T-cell leukaemia virus type-1 and type-2 (HTLV-1/2) infections. Since the United Kingdom is a low prevalence country for HTLV infections, a screening assay with high sensitivity and specificity is required. Samples with repeat reactivity on antibody testing are sent to a reference lab for confirmatory serological and molecular testing. In the case of donor screen, this leads to delays in the release of organs and can result in wastage. We aim to assess whether a signal/cut-off (S/CO) ratio higher than the manufacturer's recommendation of 1.0 in the Abbott Architect antibody assay is a reliable measure of HTLV-1/2 infection. METHODS: We conducted a 5 year retrospective analysis of 7245 patients from which 11 766 samples were tested on the Abbott Architect rHTLV I/II assay. Reactive samples (S/CO >1) were referred for confirmatory serological and molecular detection (Western Blot and proviral DNA) at UK Health Security Agency, (formerly PHE, Colindale), the national reference laboratory. Electronic, protected laboratory and hospital patient databases were employed to collate data. RESULTS: A total of 45 patients had initially reactive samples. 42.2% (n = 19/45) had an S/CO ratio > 20, with HTLV infection confirmed in n = 18/19 and indeterminate confirmatory results in n = 1/19. No samples with an S/CO ratio <4 (48.9%, n = 22/45) or 4-20 (8.9%, n = 4/45) had positive confirmatory results on subsequent confirmatory testing. CONCLUSION: Samples with an S/CO >20 likely represent a true HTLV-1/2 infection. Reactive samples with an S/CO <4 were unlikely to confirm for HTLV infections. Interpretation of these ratios can assist clinicians in the assessment of low reactive samples and reiterates the need for faster access to confirmatory testing.

Externalizing the threat from within: A new direction for researching associations between suicide and psychotic experiences.

A recent suicidal drive hypothesis posits that psychotic experiences (PEs) may serve to externalize internally generated and self-directed threat (i.e., self-injurious/suicidal behavior [SIB]) in order to optimize survival; however, it must first be demonstrated that such internal threat can both precede and inform PEs. The current study conducted the first known bidirectional analysis of SIB and PEs to test whether SIB could be considered as a plausible antecedent for PEs. Prospective data were utilized from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative birth cohort of 2232 twins, that captured SIB (any self-harm or suicidal attempt) and PEs at ages 12 and 18 years. Cross-lagged panel models demonstrated that the association between SIB at age 12 and PEs at age 18 was as strong as the association between PEs at age 12 and SIB at age 18. Indeed, the best representation of the data was a model where these paths were constrained to be equal (OR = 2.48, 95% CI = 1.63-3.79). Clinical interview case notes for those who reported both SIB and PEs at age 18, revealed that PEs were explicitly characterized by SIB/threat/death-related content for 39% of cases. These findings justify further investigation of the suicidal drive hypothesis.

The role of psychosocial factors in explaining sex differences in major depression and generalized anxiety during the COVID-19 pandemic.

BACKGROUND: Understanding how pandemics differentially impact on the socio-protective and psychological outcomes of males and females is important to develop more equitable public health policies. We assessed whether males and females differed on measures of major depression and generalized anxiety during the COVID-19 the pandemic, and if so, which sociodemographic, pandemic, and psychological variables may affect sex differences in depression and anxiety. METHODS: Participants were a nationally representative sample of Irish adults (N = 1,032) assessed between April 30th to May 19th, 2020, during Ireland's first COVID-19 nationwide quarantine. Participants completed self-report measures of anxiety (GAD-7) and depression (PHQ-9), as well as 23 sociodemographic pandemic-related, and psychological variables. Sex differences on measures of depression and anxiety were assessed using binary logistic regression analysis and differences in sociodemographic, pandemic, and psychological variables assessed using chi-square tests of independence and independent samples t-tests. RESULTS: Females were significantly more likely than males to screen positive for major depressive disorder (30.6% vs. 20.7%; χ2 (1) = 13.26, p < .001, OR = 1.69 [95% CI = 1.27, 2.25]), and generalised anxiety disorder (23.3% vs. 14.4%; χ2 (1) = 13.42, p < .001, OR = 1.81 [95% CI = 1.31, 2.49]). When adjusted for all other sex-varying covariates however, sex was no longer significantly associated with screening positive for depression (AOR = 0.80, 95% CI = 0.51, 1.25) or GAD (AOR = 0.97, 95% CI = 0.60, 1.57). CONCLUSION: Observed sex-differences in depression and anxiety during the COVID-19 pandemic in the Republic of Ireland are best explained by psychosocial factors of COVID-19 related anxiety, trait neuroticism, lower sleep quality, higher levels of loneliness, greater somatic problems, and, in the case of depression, increases in childcaring responsibilities and lower trait consciousnesses. Implications of these findings for public health policy and interventions are discussed.

Modelling the complexity of pandemic-related lifestyle quality change and mental health: an analysis of a nationally representative UK general population sample.

PURPOSE: The COVID-19 pandemic has affected the way many individuals go about their daily lives. This study attempted to model the complexity of change in lifestyle quality as a result of the COVID-19 pandemic and its context within the UK adult population. METHODS: Data from the COVID-19 Psychological Research Consortium Study (Wave 3, July 2020; N = 1166) were utilised. A measure of COVID-19-related lifestyle change captured how individuals' lifestyle quality had been altered as a consequence of the pandemic. Exploratory factor analysis and latent profile analysis were used to identify distinct lifestyle quality change subgroups, while multinomial logistic regression analysis was employed to describe class membership. RESULTS: Five lifestyle dimensions, reflecting partner relationships, health, family and friend relations, personal and social activities, and work life, were identified by the EFA, and seven classes characterised by distinct patterns of change across these dimensions emerged from the LPA: (1) better overall (3.3%), (2) worse except partner relations (6.0%), (3) worse overall (2.5%), (4) better relationships (9.5%), (5) better except partner relations (4.3%), (6) no different (67.9%), and (7) worse partner relations only (6.5%). Predictor variables differentiated membership of classes. Notably, classes 3 and 7 were associated with poorer mental health (COVID-19 related PTSD and suicidal ideation). CONCLUSIONS: Four months into the pandemic, most individuals' lifestyle quality remained largely unaffected by the crisis. Concerningly however, a substantial minority (15%) experienced worsened lifestyles compared to before the pandemic. In particular, a pronounced deterioration in partner relations seemed to constitute the more severe pandemic-related lifestyle change.

How is loneliness related to anxiety and depression: A population-based network analysis in the early lockdown period.

High risk of mental health problems is associated with loneliness resulting from social distancing measures and "lockdowns" that have been imposed globally due to the COVID-19 pandemic. This study explores the interconnectedness of loneliness, anxiety and depression on a symptom level using network analysis. A representative sample of participants (N = 1041), who were of at least 18 years of age, was recruited from the Republic of Ireland (ROI). Loneliness, anxiety and depression were assessed using validated instruments. Network analysis was used to identify the network structure of loneliness, anxiety and depression. Loneliness was found to be largely isolated from anxiety and depression nodes in the network. Anxiety and depression were largely interconnected. "Trouble relaxing," "feeling bad about oneself" and "not being able to stop or control worrying" were suggested as the most influential nodes of the network. Despite the expectation that loneliness would be implicated more robustly in the anxiety and depression network of symptoms, the results suggest loneliness as a distinct construct that is not interwoven with anxiety and depression.