Patient reported burden of asthma on resource use and productivity across 11 countries in europe

ACKNOWLEDGMENTS Sponsorship for this study and article processing charges were funded by Mundipharma International Limited (Cambridge, UK). All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published. We thank Emily Taylor, Incite Marketing Planning Limited (London, UK) for assistance in data analysis and Caoimhe McKerr (Adelphi Values, Bollington, UK) for editorial assistance. Support for this assistance was funded by Mundipharma International Limited. Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.Peer reviewedPublisher PD

Evidence of assortative mating in autism spectrum disorder

Background Assortative mating is a non-random mating system in which individuals with similar genotypes and/or phenotypes mate with one another more frequently than would be expected in a random mating system. Assortative mating has been hypothesized to play a role in Autism Spectrum Disorder (ASD) in an attempt to explain some of the increase in the prevalence of ASD that has recently been observed. ASD is considered to be a heritable neurodevelopmental disorder but there is limited understanding of its causes. Assortative mating can be explored through both phenotypic and genotypic data, but up until now, has never been investigated through genotypic measures in ASD. Methods We investigated genotypically similar mating pairs using genome-wide Single Nucleotide Polymorphism (SNP) data on trio families (Autism Genome Project (AGP) data (1,590 parents) and Simons Simplex Collection (SSC) data (1962 parents)). To determine whether or not an excess in genetic similarity was present we employed kinship coefficients and examined spousal correlation between the principal components in both the AGP and SSC datasets. We also examined assortative mating using phenotype data on the parents to detect any correlation between ASD traits. Results We found significant evidence of genetic similarity between the parents of ASD offspring using both methods in the AGP dataset. In the SSC, there was also significant evidence of genetic similarity between the parents when explored through spousal correlation. Conclusions This gives further support to the hypothesis that positive assortative mating plays a role in ASD

Managing employees with dementia: a systematic review

Background: The experience of developing dementia while in employment has been explored from the point of view of the employee, but less is known about the perspectives, experiences and needs of employers. Aims: To review systematically literature about the management of employees who develop dementia whilst in employment. Methods: Databases searched included MEDLINE, EMBASE, PsycINFO, CINAHL, BNI, ABI Inform, ISI Web of Science, Open Grey and dementia journals database; 44 documents were identified for inclusion in the review: 22 journal papers, one PhD thesis and 21 articles, reports and webpages from the grey literature. As all documents were qualitative in nature a thematic synthesis of their content was undertaken. Results: Three main themes and ten sub-themes were identified. The main themes concerned early presentation and identification in the workplace; reasonable adjustments for people with working age dementia; and the provision of information to raise awareness and facilitate informed choice. The evidence suggested that there is a lack of awareness about working age dementia and that this may impact negatively on employees. Guidance for employers offered suggestions for good practice. Conclusions: Guidance for employers is increasingly available although it rarely refers to the evidence base. There is a need for future studies that explore the effectiveness of guidance and training initiatives for employers. Examples of good practice where employees with dementia have been well supported in the workplace and who have been able to leave the workforce with dignity, would be helpful

BEACON:A Summary Framework to Overcome Potential Reimbursement Hurdles

Objective To provide a framework for addressing payers' criteria during the development of pharmaceuticals. Methods A conceptual framework was presented to an international health economic expert panel for discussion. A structured literature search (from 2010 to May 2015), using the following databases in Ovid: Medline((R)) and Medline((R)) In-Process (PubMed), Embase (Ovid), EconLit (EBSCOhost) and the National Health Service Economic Evaluation Database (NHS EED), and a 'grey literature' search, were conducted to identify existing criteria from the payer perspective. The criteria assessed by existing frameworks and guidelines were collated; the most commonly reported criteria were considered for inclusion in the framework. A mnemonic was conceived as a memory aide to summarise these criteria. Results Overall, 41 publications were identified as potentially relevant to the objective. Following further screening, 26 were excluded upon full-text review on the basis of no framework presented (n = 13), redundancy (n = 11) or abstract only (n = 2). Frameworks that captured criteria developed for or utilised by the pharmaceutical industry (n = 5) and reimbursement guidance (n = 10) were reviewed. The most commonly identified criteria-unmet need/patient burden, safety, efficacy, quality-of-life outcomes, environment, evidence quality, budget impact and comparator-were incorporated into the summary framework. For ease of communication, the following mnemonic was developed: BEACON (Burden/target population, Environment, Affordability/value, Comparator, Outcomes, Number of studies/quality of evidence). Conclusions The BEACON framework aims to capture the 'essence' of payer requirements by addressing the most commonly described criteria requested by payers regarding the introduction of a new pharmaceutical

Multi-disciplinary Evaluation of Sexual Assault Referral Centres (SARCs) for better Health (MESARCH): protocol for a 1-year cohort study examining health, well-being and cost outcomes in adult survivors of sexual assault attending SARCs in England

INTRODUCTION Sexual violence is commonplace and has serious adverse consequences for physical and mental health. Sexual Assault Referral Centres (SARCs) are viewed as a best practice response. Little is known about their effectiveness and cost-effectiveness. Long-term data on the health and well-being of those who have experienced rape and sexual assault are also lacking. METHODS AND ANALYSIS This is a mixed-methods protocol for a 1-year cohort study aiming to examine the health and well-being in survivors of sexual violence after attending a SARC in England. Quantitative measures are being taken at baseline, 6 and 12 months. Post-traumatic stress (PTS) is the primary outcome (target N=270 at 12-month follow-up). Secondary measures include anxiety, depression, substance use and sexual health and well-being. Using mixed-effects regression, our main analysis will examine whether variation in SARC service delivery and subsequent mental healthcare is associated with improvement in trauma symptoms after 12 months. An economic analysis will compare costs and outcomes associated with different organisational aspects of SARC service delivery and levels of satisfaction with care. A nested qualitative study will employ narrative analysis of transcribed interviews with 30 cohort participants and 20 survivors who have not experienced SARC services. ETHICS AND DISSEMINATION The research is supported by an independent study steering committee, data monitoring and ethics committee and patient and public involvement (PPI) group. A central guiding principle of the research is that being involved should feel diametrically opposed to being a victim of sexual violence, and be experienced as empowering and supportive. Our PPI representatives are instrumental in this, and our wider stakeholders encourage us to consider the health and well-being of all involved. We will disseminate widely through peer-reviewed articles and non-academic channels to maximise the impact of findings on commissioning of services and support for survivors. TRIAL REGISTRATION NUMBER ISRCTN30846825

Identifying schizophrenia patients who carry pathogenic genetic copy number variants using standard clinical assessment: retrospective cohort study

Background Copy number variants (CNVs) play a significant role in disease pathogenesis in a small subset of individuals with schizophrenia (~2.5%). Chromosomal microarray testing is a first-tier genetic test for many neurodevelopmental disorders. Similar testing could be useful in schizophrenia. Aims To determine whether clinically identifiable phenotypic features could be used to successfully model schizophrenia-associated (SCZ-associated) CNV carrier status in a large schizophrenia cohort. Method Logistic regression and receiver operating characteristic (ROC) curves tested the accuracy of readily identifiable phenotypic features in modelling SCZ-associated CNV status in a discovery data-set of 1215 individuals with psychosis. A replication analysis was undertaken in a second psychosis data-set (n = 479). Results In the discovery cohort, specific learning disorder (OR = 8.12; 95% CI 1.16–34.88, P = 0.012), developmental delay (OR = 5.19; 95% CI 1.58–14.76, P = 0.003) and comorbid neurodevelopmental disorder (OR = 5.87; 95% CI 1.28–19.69, P = 0.009) were significant independent variables in modelling positive carrier status for a SCZ-associated CNV, with an area under the ROC (AUROC) of 74.2% (95% CI 61.9–86.4%). A model constructed from the discovery cohort including developmental delay and comorbid neurodevelopmental disorder variables resulted in an AUROC of 83% (95% CI 52.0–100.0%) for the replication cohort. Conclusions These findings suggest that careful clinical history taking to document specific neurodevelopmental features may be informative in screening for individuals with schizophrenia who are at higher risk of carrying known SCZ-associated CNVs. Identification of genomic disorders in these individuals is likely to have clinical benefits similar to those demonstrated for other neurodevelopmental disorders

Developmental Contributions of Schizophrenia Risk Alleles and Childhood Peer Victimization to Early-Onset Mental Health Trajectories

Objective: Twin studies suggest that genetic factors contribute to continuity in mental health problems and that environmental factors are the major contributor to developmental change. The authors investigated the influence of psychiatric risk alleles on early-onset mental health trajectories and whether the trajectories were subsequently modified by exposure to childhood victimization. Methods: The sample was a prospective U.K. population-based cohort, the Avon Longitudinal Study of Parents and Children. The developmental trajectories of emotional problems were estimated in childhood (approximately ages 4–8 years) and adolescence (approximately ages 12–17 years). Psychiatric risk alleles were indexed by polygenic risk scores (PRS) for schizophrenia using genome-wide association study results from the Psychiatric Genomics Consortium. Chronic peer victimization in late childhood (ages 8.5 and 10.5 years) was assessed as an index of environmental exposure. Individuals with sufficient data on emotional problems, the PRS, and victimization were included in the main analyses (N=3,988). Results: Higher schizophrenia PRSs were associated with a trajectory of early-onset increasing emotional problems (odds ratio=1.18, 95% CI=1.02–1.36) compared with a trajectory of low-stable emotional problems. Subsequent exposure to victimization increased the likelihood of transitioning from a trajectory of low-stable emotional problems during childhood (before exposure) to an increasing trajectory in adolescence (after exposure) (odds ratio=2.59, 95% CI=1.48–4.53). Conclusions: While the early development of emotional problems was associated with genetic risk (schizophrenia risk alleles), the subsequent course of emotional problems for those who might otherwise have remained on a more favorable trajectory was altered by exposure to peer victimization, which is a potentially modifiable environmental exposure

Mental health trajectories in university students across the COVID-19 pandemic: findings from the Student Wellbeing at Northern England Universities prospective cohort study

IntroductionPsychological wellbeing in university students is receiving increased focus. However, to date, few longitudinal studies in this population have been conducted. As such, in 2019, we established the Student Wellbeing At Northern England Universities (SWANS) cohort at the University of York, United Kingdom aiming to measure student mental health and wellbeing every six months. Furthermore, the study period included the COVID-19 pandemic, giving an opportunity to track student wellbeing over time, including over the pandemic.MethodsEligible participants were invited to participate via email. Data were collected, using Qualtrics, from September 2019 to April 2021, across five waves (W1 to W5). In total, n = 4,622 students participated in at least one wave of the survey. Data collection included sociodemographic, educational, personality measures, and mental health and wellbeing. Latent profile analyses were performed, exploring trajectories of student wellbeing over the study period for those who had completed at least three of the five waves of the survey (n = 765), as measured by the Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS).ResultsFive latent profile trajectories of student wellbeing were identified. Of these, the two latent classes with initially higher wellbeing scores had broadly stable wellbeing across time (total n = 505, 66%). Two classes had lower initial scores, which lowered further across time (total n = 227, 30%). Additionally, a fifth class of students was identified who improved substantially over the study period, from a mean WEMWBS of 30.4 at W1, to 49.4 at W5 (n = 33, 4%). Risk factors for having less favourable wellbeing trajectories generally included identifying as LGBT+, self-declaring a disability, or previously being diagnosed with a mental health condition.ConclusionOur findings suggest a mixed picture of the effect of the COVID-19 pandemic on student wellbeing, with a majority showing broadly consistent levels of wellbeing across time, a smaller but still substantial group showing a worsening of wellbeing, and a small group that showed a very marked improvement in wellbeing. Those from groups traditionally underrepresented in higher education were most at risk of poorer wellbeing. This raises questions as to whether future support for wellbeing should target specific student subpopulations