Impact of COVID-19 lockdown: Domestic and child abuse in Bridgend.

INTRODUCTION: Financial stress, social stress and lack of support at home can precipitate domestic and child abuse (World Health Organization, 2020). These factors have been exacerbated by the COVID-19 pandemic (NSPCC, 2020b) (NSPCC, 2020a). We hypothesise an increase in Bridgend's domestic and child abuse during lockdown. METHOD: Data was collected retrospectively from 23rd March to 30th September 2020 and compared to the same time period in 2019. Wales-wide data on domestic abuse was shared by the Welsh Government's Live Fear free helpline. Local data was shared by domestic abuse charity CALAN, the Emergency Department (ED) and Paediatric Department of Princess of Wales Hospital (POWH). RESULTS: During lockdown, Live Fear Free reported increasing average monthly contact across Wales in 2020 (511 April; 631 December). Locally, CALAN reported a 190% increase in self-referrals and a 198% increase in third party referrals, but there was a 36% decrease in referrals from Police for domestic abuse. The Paediatric Department observed a 67% decrease in child protection medical examinations (CPMEs) undertaken (52 vs. 17). 23 examinations in 2019 were referred from schools compared to 1 in 2020. There was a greater proportion of self-referrals for CPMEs in 2020. ED child protection referrals increased from 189 (2019) to 204 (2020). CONCLUSION: There was an increase in self-referrals to local support services for domestic and child abuse concerns and an increase in referrals from families/friends for child protection concerns. This was not the case with police, ED and schools/nurseries referrals. This suggests reduced engagement with public sector organisations during lockdown which services should consider

Impact of patient and public involvement on enrolment and retention in clinical trials: Systematic review and meta-analysis

© Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to. Objective To investigate the impact of patient and public involvement (PPI) on rates of enrolment and retention in clinical trials and explore how this varies with the context and nature of PPI. Design Systematic review and meta-analysis. Data sources Ten electronic databases, including Medline, INVOLVE Evidence Library, and clinical trial registries. Eligibility criteria Experimental and observational studies quantitatively evaluating the impact of a PPI intervention, compared with no intervention or non-PPI intervention(s), on participant enrolment and/or retention rates in a clinical trial or trials. PPI interventions could include additional non-PPI components inseparable from the PPI (for example, other stakeholder involvement). Data extraction and analysis Two independent reviewers extracted data on enrolment and retention rates, as well as on the context and characteristics of PPI intervention, and assessed risk of bias. Random effects meta-analyses were used to determine the average effect of PPI interventions on enrolment and retention in clinical trials: main analysis including randomised studies only, secondary analysis adding non-randomised studies, and several exploratory subgroup and sensitivity analyses. Results 26 studies were included in the review; 19 were eligible for enrolment meta-analysis and five for retention meta-analysis. Various PPI interventions were identified with different degrees of involvement, different numbers and types of people involved, and input at different stages of the trial process. On average, PPI interventions modestly but significantly increased the odds of participant enrolment in the main analysis (odds ratio 1.16, 95% confidence interval and prediction interval 1.01 to 1.34). Non-PPI components of interventions may have contributed to this effect. In exploratory subgroup analyses, the involvement of people with lived experience of the condition under study was significantly associated with improved enrolment (odds ratio 3.14 v 1.07; P=0.02). The findings for retention were inconclusive owing to the paucity of eligible studies (odds ratio 1.16, 95% confidence interval 0.33 to 4.14), for main analysis). Conclusions These findings add weight to the case for PPI in clinical trials by indicating that it is likely to improve enrolment of participants, especially if it includes people with lived experience of the health condition under study. Further research is needed to assess which types of PPI work best in particular contexts, the cost effectiveness of PPI, the impact of PPI at earlier stages of trial design, and the impact of PPI interventions specifically targeting retention. Systematic review registration PROSPERO CRD42016043808

Associations Between Schizophrenia Polygenic Liability, Symptom Dimensions, and Cognitive Ability in Schizophrenia

Importance Schizophrenia is a clinically heterogeneous disorder. It is currently unclear how variability in symptom dimensions and cognitive ability is associated with genetic liability for schizophrenia. Objective To determine whether phenotypic dimensions within schizophrenia are associated with genetic liability to schizophrenia, other neuropsychiatric disorders, and intelligence. Design, Setting, and Participants In a genetic association study, 3 cross-sectional samples of 1220 individuals with a diagnosis of schizophrenia were recruited from community, inpatient, and voluntary sector mental health services across the UK. Confirmatory factor analysis was used to create phenotypic dimensions from lifetime ratings of the Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms, and the MATRICS Consensus Cognitive Battery. Analyses of polygenic risk scores (PRSs) were used to assess whether genetic liability to schizophrenia, other neuropsychiatric disorders, and intelligence were associated with these phenotypic dimensions. Data collection for the cross-sectional studies occurred between 1993 and 2016. Data analysis for this study occurred between January 2019 and March 2021. Main Outcomes and Measures Outcome measures included phenotypic dimensions defined from confirmatory factor analysis relating to positive symptoms, negative symptoms of diminished expressivity, negative symptoms of motivation and pleasure, disorganized symptoms, and current cognitive ability. Exposure measures included PRSs for schizophrenia, bipolar disorder, major depression, attention-deficit/hyperactivity disorder, autism spectrum disorder, and intelligence. Results Of the 1220 study participants, 817 were men (67.0%). Participants’ mean (SD) age at interview was 43.10 (12.74) years. Schizophrenia PRS was associated with increased disorganized symptom dimension scores in both a 5-factor model (β = 0.14; 95% CI, 0.07-0.22; P = 2.80 × 10−4) and a 3-factor model across all samples (β = 0.10; 95% CI, 0.05-0.15; P = 2.80 × 10−4). Current cognitive ability was associated with genetic liability to schizophrenia (β = −0.11; 95% CI, −0.19 to −0.04; P = 1.63 × 10−3) and intelligence (β = 0.23; 95% CI, 0.16-0.30; P = 1.52 × 10−10). After controlling for estimated premorbid IQ, current cognitive performance was associated with schizophrenia PRS (β = −0.08; 95% CI, −0.14 to −0.02; P = 8.50 × 10−3) but not intelligence PRS. Conclusions and Relevance The findings of this study suggest that genetic liability for schizophrenia is associated with higher disorganized dimension scores but not other symptom dimensions. Cognitive performance in schizophrenia appears to reflect distinct contributions from genetic liabilities to both intelligence and schizophrenia

Rare copy number variations are associated with poorer cognition in schizophrenia

Background Cognitive impairment in schizophrenia is a major contributor to poor outcomes yet its causes are poorly understood. Some rare copy number variants (CNVs) are associated with schizophrenia risk and impact cognition in healthy populations but their contribution to cognitive impairment in schizophrenia has not been investigated. We examined the effect of 12 schizophrenia CNVs on cognition in those with schizophrenia. Methods General cognitive ability was measured using the MATRICS composite z-score in 875 schizophrenia cases, and in a replication sample of 519 schizophrenia cases using WAIS Full-Scale IQ. Using linear regression we tested for association between cognition and schizophrenia CNV status, covarying for age and sex. In addition, we tested whether CNVs hitting genes in schizophrenia enriched gene sets (loss of function intolerant or synaptic gene sets) were associated with cognitive impairment. Results 23 schizophrenia CNV carriers were identified. Schizophrenia CNV carriers had lower general cognitive ability than non-schizophrenia CNV carriers in discovery (β=-0.66, 95%CI = -1.31 to -0.01) and replication samples (β=-0.91, 95%CI =-1.71 to -0.11), and after meta-analysis (β=-0.76, 95%CI=-1.26 to -0.25, p=0.003). CNVs hitting loss of function intolerant genes were associated with lower cognition (β= -0.15, 95%CI=-0.29 to -0.001, p=0.048). Conclusions In those with schizophrenia, cognitive ability in schizophrenia CNV carriers is 0.5-1.0 standard deviations below non-CNV carriers, which may have implications for clinical assessment and management. We also demonstrate that rare CNVs hitting genes intolerant to loss of function variation lead to more severe cognitive impairment, above and beyond the effect of known schizophrenia CNVs

Ultrarare coding variants and cognitive function in schizophrenia

Importance Impaired cognitive function in schizophrenia is associated with poor functional outcomes, but the role of rare coding variants is unclear. Objective To determine whether ultrarare constrained variants (URCVs) are associated with cognition in patients with schizophrenia. Design, Setting, and Participants Linear regression was used to perform a within-case genetic association study of URCVs and current cognition and premorbid cognitive ability. A multivariable linear regression analysis of the outcomes associated with URCVs, schizophrenia polygenic risk score, polygenic risk score for intelligence and schizophrenia associated copy number variants on cognitive ability was performed. Exome sequencing data from 802 participants with schizophrenia were assessed for current cognition using the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery and for estimated premorbid IQ using the National Adult Reading Test. Individuals were recruited from clinical and voluntary mental health services in the UK. Those with a diagnosis of intellectual disability or a neurological disorder known to affect cognition were excluded. Data collection occurred between 2007 and 2015. Data were analyzed between April 2020 and March 2022. Main Outcomes and Measures Association between URCVs, current cognition, and current cognition adjusted for premorbid IQ. Results Of the 802 participants, 499 (62%) were men and 303 (38%) were women; mean (SD) age at interview was 43.36 (11.87) years. Ultrarare constrained variants (n = 400) were associated with lower current cognition scores (β = −0.18; SE = 0.07; P = .005). In the univariable analysis, premorbid IQ was associated with URCVs (β = −0.12; SE = 0.05; P = .02) and partly attenuated the association with current cognition (β = −0.09; SE = 0.05; P = .08). Multivariable analysis showed that measured genetic factors combined accounted for 6.2% of variance in current cognition, 10.3% of variance in premorbid IQ, and supported outcomes of URCVs associated with current cognition independent of premorbid IQ (β = −0.10; SE = 0.05; P = .03). Conclusions and Relevance The findings of this study suggest that URCVs contribute to variance in cognitive function in schizophrenia, with partly independent associations before and after onset of the disorder. Although the estimated effect sizes were small, future studies may show that the effect sizes will be greater with better annotation of pathogenic variants. Genomic data may contribute to identifying those at particularly high risk of cognitive impairment in whom early remedial or preventive measures can be implemented

PIRRIST: Patient and public involvement (PPI) to enhance recruitment and retention in surgical trials

Meeting abstract from the 5th International Clinical Trials Methodology Conference (ICTMC 2019) https://ictmc2019.com

Common schizophrenia alleles are enriched in mutation-intolerant genes and maintained by background selection

Schizophrenia is a debilitating psychiatric condition often associated with poor quality of life and decreased life expectancy. Lack of progress in improving treatment outcomes has been attributed to limited knowledge of the underlying biology, although large-scale genomic studies have begun to provide such insight. We report the largest single cohort genome-wide association study of schizophrenia (11,260 cases and 24,542 controls) and through meta-analysis with existing data we identify 50 novel GWAS loci. Using gene-wide association statistics we implicate an additional set of 22 novel associations that map onto a single gene. We show for the first time that the common variant association signal is highly enriched among genes that are intolerant to loss of function mutations and that variants in these genes persist in the population despite the low fecundity associated with the disorder through the process of background selection. Associations point to novel areas of biology (e.g. metabotropic GABA-B signalling and acetyl cholinesterase), reinforce those implicated in earlier GWAS studies (e.g. calcium channel function), converge with earlier rare variants studies (e.g. NRXN1, GABAergic signalling), identify novel overlaps with autism (e.g. RBFOX1, FOXP1, FOXG1), and support early controversial candidate gene hypotheses (e.g. ERBB4 implicating neuregulin signalling). We also demonstrate the involvement of six independent central nervous system functional gene sets in schizophrenia pathophysiology. These findings provide novel insights into the biology and genetic architecture of schizophrenia, highlight the importance of mutation intolerant genes and suggest a mechanism by which common risk variants are maintained in the population

Analysis of copy number variations at 15 schizophrenia-associated loci

Background: A number of copy number variants (CNVs) have been suggested as susceptibility factors for schizophrenia. For some of these the data remain equivocal, and the frequency in individuals with schizophrenia is uncertain. Aims: To determine the contribution of CNVs at 15 schizophrenia-associated loci (a) using a large new data-set of patients with schizophrenia (n = 6882) and controls (n = 6316), and (b) combining our results with those from previous studies. Method: We used Illumina microarrays to analyse our data. Analyses were restricted to 520 766 probes common to all arrays used in the different data-sets. Results: We found higher rates in participants with schizophrenia than in controls for 13 of the 15 previously implicated CNVs. Six were nominally significantly associated (P<0.05) in this new data-set: deletions at 1q21.1, NRXN1, 15q11.2 and 22q11.2 and duplications at 16p11.2 and the Angelman/Prader-Willi Syndrome (AS/PWS) region. All eight AS/PWS duplications in patients were of maternal origin. When combined with published data, 11 of the 15 loci showed highly significant evidence for association with schizophrenia (P<4.1×10–4). Conclusions: We strengthen the support for the majority of the previously implicated CNVs in schizophrenia. About 2.5% of patients with schizophrenia and 0.9% of controls carry a large, detectable CNV at one of these loci. Routine CNV screening may be clinically appropriate given the high rate of known deleterious mutations in the disorder and the comorbidity associated with these heritable mutations

Impact of schizophrenia genetic liability on the association between schizophrenia and physical illness: a data linkage study

Background Individuals with schizophrenia are at higher risk of physical illnesses, which are a major contributor to their 20-year reduced life expectancy. It is currently unknown what causes the increased risk of physical illness in schizophrenia. Aims To link genetic data from a clinically ascertained sample of individuals with schizophrenia to anonymised NHS records. To assess (i) rates of physical illness in those with schizophrenia, and (ii) whether physical illness in schizophrenia is associated with genetic liability. Method We linked genetic data from a clinically ascertained sample of individuals with schizophrenia (CardiffCOGS, n=896) to anonymised NHS records held in the Secure Anonymised Information Linkage (SAIL) databank. Physical illnesses were defined from the General Practice Database and Patient Episode Database for Wales. Genetic liability for schizophrenia was indexed by (i) rare CNVs, and (ii) polygenic risk scores. Results Individuals with schizophrenia in SAIL had increased rates of epilepsy (standardised rate ratio (SRR)=5.34), intellectual disability (SRR=3.11), type 2 diabetes (SRR=2.45), congenital disorders (SRR=1.77), ischaemic heart disease (SRR=1.57) and smoking (SRR=1.44) in comparison to the general SAIL population. In those with schizophrenia, carrier status for schizophrenia-associated CNVs and neurodevelopmental disorderassociated CNVs was associated with height (P=0.015–0.017), with carriers being 7.5– 7.7cm shorter than non-carriers. We did not find evidence that the increased rates of poor physical health outcomes in schizophrenia are associated with genetic liability for the disorder. Conclusions This study demonstrates the value of and potential for linking genetic data from clinically ascertained research studies to anonymised health records. The increased ris

IPBES Invasive Alien Species Assessment: Chapter 1. Introducing biological invasions and the IPBES thematic assessment of invasive alien species and their control

Chapter 1: Introducing biological invasions and the IPBES thematic assessment of invasive alien species and their control of the Thematic Assessment Report on Invasive Alien Species and their Control of the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services