A telephone survey of cancer awareness among frontline staff: informing training needs

Background: Studies have shown limited awareness about cancer risk factors among hospital-based staff. Less is known about general cancer awareness among community frontline National Health Service and social care staff. Methods: A cross-sectional computer-assisted telephone survey of 4664 frontline community-based health and social care staff in North West England. Results: A total of 671 out of 4664 (14.4%) potentially eligible subjects agreed to take part. Over 92% of staff recognised most warning signs, except an unexplained pain (88.8%, n=596), cough or hoarseness (86.9%, n=583) and a sore that does not heal (77.3%, n=519). The bowel cancer-screening programme was recognised by 61.8% (n=415) of staff. Most staff agreed that smoking and passive smoking ‘increased the chance of getting cancer.’ Fewer agreed about getting sunburnt more than once as a child (78.0%, n=523), being overweight (73.5%, n=493), drinking more than one unit of alcohol per day (50.2%, n=337) or doing less than 30 min of moderate physical exercise five times a week (41.1%, n=276). Conclusion: Cancer awareness is generally good among frontline staff, but important gaps exist, which might be improved by targeted education and training and through developing clearer messages about cancer risk factors

Acute presentation of a heterotopic pregnancy following spontaneous conception: a case report

Spontaneous heterotopic pregnancy is a rare clinical condition in which intrauterine and extra uterine pregnancies occur at the same time. It can be a life threatening condition and can be easily missed with the diagnosis being overlooked. We present the case of a 40 year old patient who was treated for a heterotopic pregnancy. She had a transvaginal ultrasound because of a previous ectopic pregnancy and an intrauterine gestational sac was seen with false reassurances. The patient presented acutely with a ruptured tubal pregnancy and this was managed laparoscopically. The ectopic pregnancy was not suspected at her initial presentation. A high index of suspicion is needed in women with risk factors for an ectopic pregnancy and in low risk women who have free fluid with or without an adnexal mass with an intrauterine gestation

Gene-environment correlations and causal effects of childhood maltreatment on physical and mental health: a genetically informed approach.

BACKGROUND: Childhood maltreatment is associated with poor mental and physical health. However, the mechanisms of gene-environment correlations and the potential causal effects of childhood maltreatment on health are unknown. Using genetics, we aimed to delineate the sources of gene-environment correlation for childhood maltreatment and the causal relationship between childhood maltreatment and health. METHODS: We did a genome-wide association study meta-analysis of childhood maltreatment using data from the UK Biobank (n=143 473), Psychiatric Genomics Consortium (n=26 290), Avon Longitudinal Study of Parents and Children (n=8346), Adolescent Brain Cognitive Development Study (n=5400), and Generation R (n=1905). We included individuals who had phenotypic and genetic data available. We investigated single nucleotide polymorphism heritability and genetic correlations among different subtypes, operationalisations, and reports of childhood maltreatment. Family-based and population-based polygenic score analyses were done to elucidate gene-environment correlation mechanisms. We used genetic correlation and Mendelian randomisation analyses to identify shared genetics and test causal relationships between childhood maltreatment and mental and physical health conditions. FINDINGS: Our meta-analysis of genome-wide association studies (N=185 414) identified 14 independent loci associated with childhood maltreatment (13 novel). We identified high genetic overlap (genetic correlations 0·24-1·00) among different maltreatment operationalisations, subtypes, and reporting methods. Within-family analyses provided some support for active and reactive gene-environment correlation but did not show the absence of passive gene-environment correlation. Robust Mendelian randomisation suggested a potential causal role of childhood maltreatment in depression (unidirectional), as well as both schizophrenia and ADHD (bidirectional), but not in physical health conditions (coronary artery disease, type 2 diabetes) or inflammation (C-reactive protein concentration). INTERPRETATION: Childhood maltreatment has a heritable component, with substantial genetic correlations among different operationalisations, subtypes, and retrospective and prospective reports of childhood maltreatment. Family-based analyses point to a role of active and reactive gene-environment correlation, with equivocal support for passive correlation. Mendelian randomisation supports a (primarily bidirectional) causal role of childhood maltreatment on mental health, but not on physical health conditions. Our study identifies research avenues to inform the prevention of childhood maltreatment and its long-term effects. FUNDING: Wellcome Trust, UK Medical Research Council, Horizon 2020, National Institute of Mental Health, and National Institute for Health Research Biomedical Research Centre.This work was supported by the Wellcome Trust (Grant refs: 214322/Z/18/Z, 104036/Z/14/Z, 204623/Z/16/Z, and 217065/Z/19/Z). VW was funded by the Bowring Research Fellowship from St. Catharine’s College, Cambridge and Wellcome Trust Collaborative Award (Grant Ref: 214322/Z/18/Z). ASFK and AM are supported by Wellcome Trust Grant 104036/Z/14/Z. ASFK is also supported by an ESRC Postdoctoral Fellowship (Grant ref: ES/V011650/1). ML is supported by the scholarship from the China Scholarship Council (No. 201706990036). The work of CC has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie grant agreement No 707404 and grant agreement No 848158 (EarlyCause Project). MHvIJ is supported by the Dutch Ministry of Education, Culture, and Science and the Netherlands Organization for Scientific Research (NWO grant No. 024.001.003, Consortium on Individual Development) and by a Spinoza Prize of the Netherlands Organization for Scientific Research. HMS and MRM are supported by the Medical Research Council and the University of Bristol (MC_UU_00011/7) and by the National Institute for Health Research (NIHR) Biomedical Research Centre at the University Hospitals Bristol National Health Service Foundation Trust and the University of Bristol. HMS is also supported by the European Research Council (Grant ref: 758813 MHINT). CMN is supported by the National Institute for Mental Health NIMH R01MH106595 and the Center of Excellence for Stress and Mental Health (CESAMH), Veterans Affairs San Diego. AJG and SB are supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (grant number 204623/Z/16/Z). TMM and RB are supported by the NIMH (R01MH117014, TMM; K23MH120437, RB).The research was conducted in association with the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, and the NIHR Collaboration for Leadership in Applied Health Research and Care East of England at Cambridgeshire and Peterborough NHS Foundation Trust. The views expressed are those of the author(s) and not necessarily those of the National Health Service, the NIHR, or the Department of Health and Social Care. This research was possible due to two applications to the UK Biobank: Projects 20904 and 23787. This research was co-funded by the NIHR Cambridge Biomedical Research Centre and a Marmaduke Sheild grant. The UK Medical Research Council and Wellcome (Grant Ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. The study website contains details of all data available through a fully searchable data dictionary (http://www.bristol.ac.uk/alspac/researchers/our-data/). Part of this data was collected using REDCap, see the REDCap website for details https://projectredcap.org/resources/citations/). The first phase of the Generation R Study is made possible by financial support from the Erasmus Medical Centre, Rotterdam; the Erasmus University Rotterdam; ZonMw; the Netherlands Organization for Scientific Research (NWO); and the Ministry of Health, Welfare and Sport. The authors gratefully acknowledge the contribution of all children and parents, general practitioners, hospitals, midwives and pharmacies involved in the Generation R Study. The Generation R Study is conducted by the Erasmus Medical Center in close collaboration with the School of Law and Erasmus School of Social and Behavioural Sciences at Erasmus University Rotterdam; the Municipal Health Service Rotterdam area, Rotterdam; the Rotterdam Homecare Foundation, Rotterdam; and the Stichting Trombosedienst & Artsenlaboratorium Rijnmond (STAR-MDC), Rotterdam

Adolescent brain maturation and cortical folding: evidence for reductions in gyrification

Evidence from anatomical and functional imaging studies have highlighted major modifications of cortical circuits during adolescence. These include reductions of gray matter (GM), increases in the myelination of cortico-cortical connections and changes in the architecture of large-scale cortical networks. It is currently unclear, however, how the ongoing developmental processes impact upon the folding of the cerebral cortex and how changes in gyrification relate to maturation of GM/WM-volume, thickness and surface area. In the current study, we acquired high-resolution (3 Tesla) magnetic resonance imaging (MRI) data from 79 healthy subjects (34 males and 45 females) between the ages of 12 and 23 years and performed whole brain analysis of cortical folding patterns with the gyrification index (GI). In addition to GI-values, we obtained estimates of cortical thickness, surface area, GM and white matter (WM) volume which permitted correlations with changes in gyrification. Our data show pronounced and widespread reductions in GI-values during adolescence in several cortical regions which include precentral, temporal and frontal areas. Decreases in gyrification overlap only partially with changes in the thickness, volume and surface of GM and were characterized overall by a linear developmental trajectory. Our data suggest that the observed reductions in GI-values represent an additional, important modification of the cerebral cortex during late brain maturation which may be related to cognitive development

Inhibition of apoptosis in neuronal cells infected with Chlamydophila (Chlamydia) pneumoniae

Background Chlamydophila (Chlamydia) pneumoniae is an intracellular bacterium that has been identified within cells in areas of neuropathology found in Alzheimer disease (AD), including endothelia, glia, and neurons. Depending on the cell type of the host, infection by C. pneumoniae has been shown to influence apoptotic pathways in both pro- and anti-apoptotic fashions. We have hypothesized that persistent chlamydial infection of neurons may be an important mediator of the characteristic neuropathology observed in AD brains. Chronic and/or persistent infection of neuronal cells with C. pneumoniae in the AD brain may affect apoptosis in cells containing chlamydial inclusions. Results SK-N-MC neuroblastoma cells were infected with the respiratory strain of C. pneumoniae, AR39 at an MOI of 1. Following infection, the cells were either untreated or treated with staurosporine and then examined for apoptosis by labeling for nuclear fragmentation, caspase activity, and membrane inversion as indicated by annexin V staining. C. pneumoniae infection was maintained through 10 days post-infection. At 3 and 10 days post-infection, the infected cell cultures appeared to inhibit or were resistant to the apoptotic process when induced by staurosporine. This inhibition was demonstrated quantitatively by nuclear profile counts and caspase 3/7 activity measurements. Conclusion These data suggest that C. pneumoniae can sustain a chronic infection in neuronal cells by interfering with apoptosis, which may contribute to chronic inflammation in the AD brai

Psychological Distress Before and During the COVID-19 Pandemic Among Adults in the United Kingdom Based on Coordinated Analyses of 11 Longitudinal Studies

Importance: How population mental health has evolved across the COVID-19 pandemic under varied lockdown measures is poorly understood, and the consequences for health inequalities are unclear. Objective: To investigate changes in mental health and sociodemographic inequalities from before and across the first year of the COVID-19 pandemic in 11 longitudinal studies. Design, Setting, and Participants: This cohort study included adult participants from 11 UK longitudinal population-based studies with prepandemic measures of psychological distress. Analyses were coordinated across these studies, and estimates were pooled. Data were collected from 2006 to 2021. Exposures: Trends in the prevalence of poor mental health were assessed in the prepandemic period (time period 0 [TP 0]) and at 3 pandemic TPs: 1, initial lockdown (March to June 2020); 2, easing of restrictions (July to October 2020); and 3, a subsequent lockdown (November 2020 to March 2021). Analyses were stratified by sex, race and ethnicity, education, age, and UK country. Main Outcomes and Measures: Multilevel regression was used to examine changes in psychological distress from the prepandemic period across the first year of the COVID-19 pandemic. Psychological distress was assessed using the 12-item General Health Questionnaire, the Kessler 6, the 9-item Malaise Inventory, the Short Mood and Feelings Questionnaire, the 8-item or 9-item Patient Health Questionnaire, the Hospital Anxiety and Depression Scale, and the Centre for Epidemiological Studies–Depression across different studies. Results: In total, 49 993 adult participants (12 323 [24.6%] aged 55-64 years; 32 741 [61.2%] women; 4960 [8.7%] racial and ethnic minority) were analyzed. Across the 11 studies, mental health deteriorated from prepandemic scores across all 3 pandemic periods, but there was considerable heterogeneity across the study-specific estimated effect sizes (pooled estimate for TP 1: standardized mean difference [SMD], 0.15; 95% CI, 0.06-0.25; TP 2: SMD, 0.18; 95% CI, 0.09-0.27; TP 3: SMD, 0.21; 95% CI, 0.10-0.32). Changes in psychological distress across the pandemic were higher in women (TP 3: SMD, 0.23; 95% CI, 0.11, 0.35) than men (TP 3: SMD, 0.16; 95% CI, 0.06-0.26) and lower in individuals with below–degree level education at TP 3 (SMD, 0.18; 95% CI, 0.06-0.30) compared with those who held degrees (SMD, 0.26; 95% CI, 0.14-0.38). Increased psychological distress was most prominent among adults aged 25 to 34 years (SMD, 0.49; 95% CI, 0.14-0.84) and 35 to 44 years (SMD, 0.35; 95% CI, 0.10-0.60) compared with other age groups. No evidence of changes in distress differing by race and ethnicity or UK country were observed. Conclusions and Relevance: In this study, the substantial deterioration in mental health seen in the UK during the first lockdown did not reverse when lockdown lifted, and a sustained worsening was observed across the pandemic period. Mental health declines have been unequal across the population, with women, those with higher degrees, and those aged 25 to 44 years more affected than other groups

Non-Compliance with Growth Hormone Treatment in Children Is Common and Impairs Linear Growth

BACKGROUND: GH therapy requires daily injections over many years and compliance can be difficult to sustain. As growth hormone (GH) is expensive, non-compliance is likely to lead to suboptimal growth, at considerable cost. Thus, we aimed to assess the compliance rate of children and adolescents with GH treatment in New Zealand. METHODS: This was a national survey of GH compliance, in which all children receiving government-funded GH for a four-month interval were included. Compliance was defined as ≥ 85% adherence (no more than one missed dose a week on average) to prescribed treatment. Compliance was determined based on two parameters: either the number of GH vials requested (GHreq) by the family or the number of empty GH vials returned (GHret). Data are presented as mean ± SEM. FINDINGS: 177 patients were receiving GH in the study period, aged 12.1 ± 0.6 years. The rate of returned vials, but not number of vials requested, was positively associated with HVSDS (p < 0.05), such that patients with good compliance had significantly greater linear growth over the study period (p<0.05). GHret was therefore used for subsequent analyses. 66% of patients were non-compliant, and this outcome was not affected by sex, age or clinical diagnosis. However, Maori ethnicity was associated with a lower rate of compliance. INTERPRETATION: An objective assessment of compliance such as returned vials is much more reliable than compliance based on parental or patient based information. Non-compliance with GH treatment is common, and associated with reduced linear growth. Non-compliance should be considered in all patients with apparently suboptimal response to GH treatment